PMID- 27386998 TI - Detailed off-gas measurements for improved modelling of the aeration performance at the WWTP of Eindhoven. AB - At wastewater treatment plants (WWTPs), the aerobic conversion processes in the bioreactor are driven by the presence of dissolved oxygen (DO). Within these conversion processes, the oxygen transfer is a rate limiting step as well as being the largest energy consumer. Despite this high importance, WWTP models often lack detail on the aeration part. An extensive measurement campaign with off-gas tests was performed at the WWTP of Eindhoven to provide more information on the performance and behaviour of the aeration system. A high spatial and temporal variability in the oxygen transfer efficiency was observed. Applying this gathered system knowledge in the aeration model resulted in an improved prediction of the DO concentrations. Moreover, an important consequence of this was that ammonium predictions could be improved by resetting the ammonium half saturation index for autotrophs to its default value. This again proves the importance of balancing sub-models with respect to the need for model calibration as well as model predictive power. PMID- 27386999 TI - The effect of lime-dried sewage sludge on the heat-resistance of eco-cement. AB - The treatment and disposal of sewage sludge is a growing problem for sewage treatment plants. One method of disposal is to use sewage sludge as partial replacement for raw material in cement manufacture. Although this process has been well researched, little attention has been given to the thermal properties of cement that has had sewage sludge incorporated in the manufacturing process. This study investigated the fire endurance of eco-cement to which lime-dried sludge (LDS) had been added. LDS was added in proportions of 0%, 3%, 6%, 9%, and 12% (by weight) to the raw material. The eco-cement was exposed to 200, 400, or 600 degrees C for 3 h. The residual strength and the microstructural properties of eco-cement were then studied. Results showed that the eco-cement samples suffered less damage than conventional cement at 600 degrees C. The microstructural studies showed that LDS incorporation could reduce Ca(OH)(2) content. It was concluded that LDS has the potential to improve the heat resistance of eco-cement products. PMID- 27387000 TI - Standardized characterization procedures: a necessary support to regulations. AB - Sustainable procedures for sludge/biosolids management require the development of strategies to reduce the amount of sludge to be handled and to produce higher quality biosolids. Therefore, realistic and enforceable regulations adapted to local situations must be developed, defined outlet procedures established and good quality products guaranteed. To this end, the definition of standardized characterization procedures and guidelines for good practices becomes a necessary support to regulations. To contribute to the development of the EU directives dealing with sludge, the European Committee for Standardization (CEN) has established Technical Committee 308 (TC 308) whose scope is the standardization of methods for sludge characterization and the production of guidelines of good practice. In this paper, the most recent developments of the CEN/TC 308 work for the chemical, biological and physical characterization of sludge/biosolids are discussed in relation to the main different treatment and outlet options. PMID- 27387001 TI - Removal of hexavalent chromium from aqueous solution by calcined Zn/Al-LDHs. AB - In this study, Zn/Al-layered double hydroxides (Zn/Al-LDHs) were synthesized by a co-precipitation method and characterized with X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Then the hexavalent chromium Cr(VI) adsorption experiments on calcined Zn/Al-LDHs were carried out to analyze the effects of pH, temperature, adsorption time, initial Cr(VI) concentration and adsorbent dosage on the removal of Cr(VI) from aqueous solutions. The maximum adsorption capacity for Cr(VI) on calcined Zn/Al-LDHs under optimal conditions was found to be over 120 mg/g. The kinetic and isotherm of Cr(VI) adsorption on calcined Zn/Al-LDHs can be described with the pseudo second-order kinetic model and Langmuir isotherm, respectively. PMID- 27387002 TI - Carbonized medlar-core particles as a new biosorbent for removal of Cu(2+) from aqueous solution and study of its surface morphology. AB - The objective of this study was to investigate the use of carbonized medlar-core particles as a new biosorbent to remove Cu(2+) from aqueous solution. Fourier transform infrared spectroscopy and scanning electron microscopy were used to characterize the biosorbent. This paper reports the effects of adsorbent dose, pH, temperature and concentration of adsorbate. Batch isotherm studies were also performed to understand the ability of the adsorbent. The adsorption behavior of the Cu(2+) was studied using Langmuir and Freundlich adsorption isotherm models. The maximum adsorption capacity determined from the Langmuir adsorption equation has been found as 43.478 mg.g(-1) at 298.15 K. The adsorption of Cu(2+) by medlar core in carbonized form was spontaneous and endothermic. It was also found that the biosorption of Cu(2+) followed second-order kinetics. Carbonized medlar-core particles showed great potential in aqueous solution due to the high adsorption capacity. PMID- 27387003 TI - Post-treatment of sanitary landfill leachate by coagulation-flocculation using chitosan as primary coagulant. AB - Chitosan was chosen as an alternative primary coagulant in a complementary coagulation-flocculation treatment of sanitary landfill leachate with the aim of removing recalcitrant organic matter. In order to optimize the process conditions, central composite design and response surface methodology were applied. To evaluate the performance of the process using chitosan, we also carried out tests with aluminium sulphate (Al(2) (SO(4))(3).14 H(2)O) as coagulant. In addition, acute toxicity tests were carried using the duckweed Lemna minor and the guppy fish Poecilia reticulata as test organisms. The analytic hierarchy process was employed for selecting the most appropriate coagulant. Mean values of true colour removal efficiency of 80% and turbidity removal efficiency of 91.4% were reached at chitosan dosages of 960 mg L(-1) at pH 8.5. The acute toxicity tests showed that organisms were sensitive to all samples, mainly after coagulation-flocculation using chitosan. CE(50) for L. minor was not determined because there was no inhibition of the average growth rate and biomass production; LC(50) for P. reticulata was 23% (v v(-1)). Multi criteria analysis showed that alum was the most appropriate coagulant. Therefore, chitosan as primary coagulant was not considered to be a viable alternative in the post-treatment of landfill leachate. PMID- 27387004 TI - Removal of Pb(II) from aqueous solutions by graphene oxide aerogels. AB - This paper reports the application of graphene oxide aerogels (GOAs) for adsorption of lead(II) ions from aqueous solutions. The aerogels were fabricated from graphene oxide (GO) colloidal suspensions by unidirectional freeze drying method. The synthesized GO powders, as well as the aerogels, were thoroughly characterized by various techniques. The experimental data showed that the kinetic of adsorption followed a pseudo-second-order model with sharp lead(II) ions uptake within the first 90 min. Kinetic data analysis revealed that the adsorption process was controlled by film diffusion mechanism. The equilibrium data were best fitted to Langmuir model and the qmax was calculated to be as high as 158 mg/g. Thermodynamic analysis demonstrated that the adsorption process was spontaneous and endothermic with increased randomness at the solid-liquid interface. Experiments showed that almost all the adsorbed ions could desorb into the solution only by decreasing the solution pH below the isoelectric point of the adsorbent. In addition to abundant oxygen containing functional groups existing on the surface of GO sheets, high porosity and surface area of the aerogel are believed to be influential factors in the adsorption process. PMID- 27387005 TI - Mechanisms on formation of hierarchically porous carbon and its adsorption behaviors. AB - Using simple one-step carbonization-activation, the residues of paulownia flowers are employed as a precursor to prepare hierarchically porous activated carbon. After investigating the optimum conditions, the obtained paulownia flowers based activated carbon (PFAC) is characterized by Fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscope, Brunauer-Emmett-Teller specific surface area analysis (S(BET)), thermo gravimetric analysis, and X-ray photoelectron spectroscopy. The PFAC owns a high specific surface area of 1,053 m(2)/g as well as a hierarchically porous structure with a combination of micro-, meso- and macropores. The pore-forming mechanism is discussed according to results of characterization. Using methylene blue as model dye, the adsorption behaviors of PFAC were investigated. We found that the dye could be rapidly adsorbed by hierarchically porous PFAC, and the adsorption capacity of PFAC reached 300 mg/g. PMID- 27387006 TI - Adsorptive removal of PPCPs by biomorphic HAP templated from cotton. AB - Biomorphic nano-hydroxyapatite (HAP) was fabricated by a co-precipitation method using cotton as bio-templates and employed in adsorptive removal of ofloxacin (OFL) and triclosan (TCS) that are two representative pharmaceuticals and personal care products (PPCPs). The surface area and porosity, crystal phase, functional group, morphology and micro-structure of the synthesized HAP were characterized by Brunauer-Emmett-Teller isotherm, X-ray powder diffraction, Fourier transform infrared spectroscopy, scanning electron macroscopic and transmission electron microscopy. The effects of initial pH, ionic strength, initial concentration, contact time and temperature on the removal of PPCPs were studied in a batch experiment. The adsorption of OFL and TCS was rapid and almost accomplished within 50 min. Kinetic studies indicated that the adsorption process of OFL and TCS followed the pseudo-first-order and pseudo-second-order models, respectively. The Freundlich isotherm described the OFL adsorption process well but the adsorption of TCS fitted the Langmuir isotherm better. Thermodynamics and isotherm parameters suggested that both OFL and TCS adsorption were feasible and spontaneous. Hydrogen bond and Lewis acid-base reaction may be the dominating adsorption mechanism of OFL and TCS, respectively. Compared to other adsorbents, biomorphic HAP is environmentally friendly and has the advantages of high adsorption capacity, exhibiting potential application for PPCPs removal. PMID- 27387007 TI - Sorption of paracetamol onto biomaterials. AB - Pharmaceutical residues released into the environment are posing more and more public health problems. It is worthwhile to study the retention of pharmaceuticals residues by adsorption on solid supports. Batch sorption experiments are intended to identify the adsorption isotherms of the pharmaceutically active ingredient on the biomaterials. The results obtained in this study have shown that the retention possibilities of these compounds by bio adsorbents (clay and sand) are not significant. The negligible sorption for these media is explained by the low hydrophobicity of paracetamol (Log K(ow) = 0.46). The retention of paracetamol on the dehydrated sewage sludge and on Posidonia oceanica showed a relatively significant adsorption with a maximal quantity of 0.956 mg g(-1) and 1.638 mg g(-1) for the dehydrate sludge and P. oceanica, respectively. On the other hand, the study of paracetamol retention on the powdered activated carbon showed a high adsorption capacity of about 515.27 mg g( 1). Isotherm data show a good fit with Langmuir's model. An infrared analysis is carried out. It shows identical bands before and after adsorption, with some modifications. PMID- 27387008 TI - Thermodynamically-Weighted Conformational Ensemble of Cyclic RGD Peptidomimetics from NOE Data. AB - In the case of flexible molecules, the standard approach of transforming NOE intensities into spatial restraints and of building conformational models minimizing these restraints greatly neglects the richness of molecular conformations. Making use of NOE intensities measured in triplicate and of an iterative molecular-dynamics scheme, we optimized a force field to generate a set of conformations whose ensemble is compatible with the experimental data, and is weighted according to the Boltzmann distribution. This scheme is applied to two cyclic peptidomimetic ligands of integrins. Their difference in binding affinity is recapitulated in terms of their difference in conformational fluctuations. PMID- 27387009 TI - What's My Substrate? Computational Function Assignment of Candida parapsilosis ADH5 by Genome Database Search, Virtual Screening, and QM/MM Calculations. AB - Zinc-dependent medium chain reductase from Candida parapsilosis can be used in the reduction of carbonyl compounds to pharmacologically important chiral secondary alcohols. To date, the nomenclature of cpADH5 is differing (CPCR2/RCR/SADH) in the literature, and its natural substrate is not known. In this study, we utilized a substrate docking based virtual screening method combined with KEGG, MetaCyc pathway, and Candida genome databases search for the discovery of natural substrates of cpADH5. The virtual screening of 7834 carbonyl compounds from the ZINC database provided 94 aldehydes or methyl/ethyl ketones as putative carbonyl substrates. Out of which, 52 carbonyl substrates of cpADH5 with catalytically active docking pose were identified by employing mechanism based substrate docking protocol. Comparison of the virtual screening results with KEGG, MetaCyc database search, and Candida genome pathway analysis suggest that cpADH5 might be involved in the Ehrlich pathway (reduction of fusel aldehydes in leucine, isoleucine, and valine degradation). Our QM/MM calculations and experimental activity measurements affirmed that butyraldehyde substrates are the potential natural substrates of cpADH5, suggesting a carbonyl reductase role for this enzyme in butyraldehyde reduction in aliphatic amino acid degradation pathways. Phylogenetic tree analysis of known ADHs from Candida albicans shows that cpADH5 is close to caADH5. We therefore propose, according to the experimental substrate identification and sequence similarity, the common name butyraldehyde dehydrogenase cpADH5 for Candida parapsilosis CPCR2/RCR/SADH. PMID- 27387010 TI - Direct Imaging of Long-Range Exciton Transport in Quantum Dot Superlattices by Ultrafast Microscopy. AB - Long-range charge and exciton transport in quantum dot (QD) solids is a crucial challenge in utilizing QDs for optoelectronic applications. Here, we present a direct visualization of exciton diffusion in highly ordered CdSe QDs superlattices by mapping exciton population using ultrafast transient absorption microscopy. A temporal resolution of ~200 fs and a spatial precision of ~50 nm of this technique provide a direct assessment of the upper limit for exciton transport in QD solids. An exciton diffusion length of ~125 nm has been visualized in the 3 ns experimental time window and an exciton diffusion coefficient of (2.5 +/- 0.2) * 10(-2) cm(2) s(-1) has been measured for superlattices constructed from 3.6 nm CdSe QDs with center-to-center distance of 6.7 nm. The measured exciton diffusion constant is in good agreement with Forster resonance energy transfer theory. We have found that exciton diffusion is greatly enhanced in the superlattices over the disordered films with an order of magnitude higher diffusion coefficient, pointing toward the role of disorder in limiting transport. This study provides important understandings on energy transport mechanisms in both the spatial and temporal domains in QD solids. PMID- 27387011 TI - Activation of Oxygen and Hydrogen Peroxide by Copper(II) Coupled with Hydroxylamine for Oxidation of Organic Contaminants. AB - This study reports that the combination of Cu(II) with hydroxylamine (HA) (referred to herein as Cu(II)/HA system) in situ generates H2O2 by reducing dissolved oxygen, subsequently producing reactive oxidants through the reaction of Cu(I) with H2O2. The external supply of H2O2 to the Cu(II)/HA system (i.e., the Cu(II)/H2O2/HA system) was found to further enhance the production of reactive oxidants. Both the Cu(II)/HA and Cu(II)/H2O2/HA systems effectively oxidized benzoate (BA) at pH between 4 and 8, yielding a hydroxylated product, p hydroxybenzoate (pHBA). The addition of a radical scavenger, tert-butyl alcohol, inhibited the BA oxidation in both systems. However, electron paramagnetic resonance (EPR) spectroscopy analysis indicated that (*)OH was not produced under either acidic or neutral pH conditions, suggesting that the alternative oxidant, cupryl ion (Cu(III)), is likely a dominant oxidant. PMID- 27387013 TI - Development of core-shell coaxially electrospun composite PCL/chitosan scaffolds. AB - This study was related to combining of synthetic Poly (epsilon-caprolactone) (PCL) and natural chitosan polymers to develop three dimensional (3D) PCL/chitosan core-shell scaffolds for tissue engineering applications. The scaffolds were fabricated with coaxial electrospinning technique and the characterizations of the samples were done by thickness and contact angle (CA) measurements, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray Photoelectron Spectroscopy (XPS) analyses, mechanical and PBS absorption and shrinkage tests. The average inter-fiber diameter values were calculated for PCL (0.717+/-0.001MUm), chitosan (0.660+/-0.007MUm) and PCL/chitosan core-shell scaffolds (0.412+/-0.003MUm), also the average inter fiber pore size values exhibited decreases of 66.91% and 61.90% for the PCL and chitosan scaffolds respectively, compared to PCL/chitosan core-shell ones. XPS analysis of the PCL/chitosan core-shell structures exhibited the characteristic peaks of PCL and chitosan polymers. The cell culture studies (MTT assay, Confocal Laser Scanning Microscope (CLSM) and SEM analyses) carried out with L929 ATCC CCL 1 mouse fibroblast cell line proved that the biocompatibility performance of the scaffolds. The obtained results showed that the created micro/nano fibrous structure of the PCL/chitosan core-shell scaffolds in this study increased the cell viability and proliferation on/within scaffolds. PMID- 27387012 TI - Ligand Binding Enhances Millisecond Conformational Exchange in Xylanase B2 from Streptomyces lividans. AB - Xylanases catalyze the hydrolysis of xylan, an abundant carbon and energy source with important commercial ramifications. Despite tremendous efforts devoted to the catalytic improvement of xylanases, success remains limited because of our relatively poor understanding of their molecular properties. Previous reports suggested the potential role of atomic-scale residue dynamics in modulating the catalytic activity of GH11 xylanases; however, dynamics in these studies was probed on time scales orders of magnitude faster than the catalytic time frame. Here, we used nuclear magnetic resonance titration and relaxation dispersion experiments ((15)N-CPMG) in combination with X-ray crystallography and computational simulations to probe conformational motions occurring on the catalytically relevant millisecond time frame in xylanase B2 (XlnB2) and its catalytically impaired mutant E87A from Streptomyces lividans 66. Our results show distinct dynamical properties for the apo and ligand-bound states of the enzymes. The apo form of XlnB2 experiences conformational exchange for residues in the fingers and palm regions of the catalytic cleft, while the catalytically impaired E87A variant displays millisecond dynamics only in the fingers, demonstrating the long-range effect of the mutation on flexibility. Ligand binding induces enhanced conformational exchange of residues interacting with the ligand in the fingers and thumb loop regions, emphasizing the potential role of residue motions in the fingers and thumb loop regions for recognition, positioning, processivity, and/or stabilization of ligands in XlnB2. To the best of our knowledge, this work represents the first experimental characterization of millisecond dynamics in a GH11 xylanase family member. These results offer new insights into the potential role of conformational exchange in GH11 enzymes, providing essential dynamic information to help improve protein engineering and design applications. PMID- 27387014 TI - Fabrication and performance characteristics of tough hydrogel scaffolds based on biocompatible polymers. AB - Novel silane crosslinked tough hydrogel scaffolds were prepared using chitosan (CS) and polyvinyl alcohol (PVA) to give network structure and scaffolds properties. The influence of crosslinking and PVA concentration on scaffolds were studied. Fourier transform infrared spectroscopy (FTIR) spectroscopy confirmed the presence of incorporated components. Tensile strength (TS) and fracture strain analysis of scaffolds were detected owing to the mutual effect of chemically and physically crosslinked network. Tough hydrogel scaffolds having 90% CS and 10% PVA exhibited TS of 49.18MPa and 10.15% elongation at break. The contact angle is less than 90 degrees exhibited the hydrophilic nature of the scaffold. X-ray diffraction analysis (XRD) indicated the characteristics peaks fitting to CS and PVA and increase in the crystallinity of scaffolds. Cytotoxicity of scaffolds with different human fibroblast cell lines (F121, F192 and F84) for indirect method and human dermal fibroblast cell lines (F121) for direct method was evaluated. This indicated that these biomaterials were non toxic, viable to the used cell lines, helpful in the growth of these cells and did not discharge toxic material damaging to the living cells. PMID- 27387015 TI - Preparation, characterization and antiglycation activities of the novel polysaccharides from Boletus snicus. AB - Boletus snicus (BS) is one of the commercially important mushroom species. Two polysaccharides (BSP-1b and BSP-2b) were extracted and purified from the body of BS by DEAE-cellulose and Sephadex G-100 column chromatography. The average of molecular weight of BSP-1b and BSP-2b were 59.21kDa and 128.74kDa. BSP-1b is a heteropolysaccharide with a large number of glucose and a small amount of mannose, glucosamine hydrochloride and arabinose. The monosaccharide compositions of BSP-2b contain mannose, glucuronic acid, glucosamine hydrochloride, glucose, galactose, arabinose with the molar ratio of 10.70:6.95:12.05:12.57:1.83:1.00. The FTIR spectra and NMR analysis demonstrated that BSP-1b and BSP-2b existed pyranose ring structure and BSP-2b had high content of uronic acid. The antiglycation activities of BSP-1b and BSP-2b were investigated. The results showed BSP-1b and BSP-2b had high inhibitory effects on glycation and exhibited dose-dependent responses. BSP-2b showed stronger antiglycation activity than BSP 1b. This study indicated that the BSP-2b could effectively inhibit the formation of advanced glycation end-products. PMID- 27387016 TI - Biochemical and molecular characterization of new keratinoytic protease from Actinomadura viridilutea DZ50. AB - A new extracellular thermostable keratinolytic protease, designated KERDZ, was purified and characterized from a thermophilic actinomycetes Actinomadura viridilutea DZ50 isolated from Algerian fishing port. The isolate exhibited high keratinase production when grown in chicken-feather meal media (18,000U/ml) after 96-h of incubation at 45 degrees C. The enzyme was purified by ammonium sulfate precipitation (35-55%)-dialysis and heat treatment (30min at 75 degrees C) followed by UNO S-1 FPLC cation exchange chromatography and size exclusion HPLC column. The biochemical characterizations carried on include physico-chemical determination and spectroscopic analysis. The MALDI-TOF/MS analysis revealed that the purified enzyme was a monomer with a molecular mass of 19536.10-Da. The sequence of the 25 N-terminal residues of KERDZ showed high homology with those of actinomycetes keratinases. Optimal activity was achieved at pH 11 and 80 degrees C. KERDZ was completely inhibited by PMSF and DFP suggested its belonging to the serine keratinase family. KERDZ displayed higher levels of hydrolysis and catalytic efficiency than bacterial keratinases (KERAK-29, Actinase E, and KERAB) and subtilisins (subtilisin Carlsberg and subtilisin Novo). The kerDZ gene encoding KERDZ was isolated and its DNA sequence was determined. These properties make KERDZ a potential, promising and eco-friendly alternative to the conventional chemicals used for industrial applications. PMID- 27387017 TI - Antibacterial Effect of Silver-Incorporated Flake-Shell Nanoparticles under Dual Modality. AB - Silver has been recognized as a broad-spectrum antimicrobial agent and extensively used in biomedical applications. Through a sequential one-pot synthesis strategy, we have successfully incorporated silver into flake-shell nanoparticles. Due to the simultaneous growth of networked nanostructures of silica and in situ reduction of silver ions, homogeneously distributed silver into the shell of the nanocapsule was formed. The antibacterial test indicated that the silver-incorporated silica nanocapsule exhibits effective antibacterial activity, inhibiting the bacterial growth by 75%. In addition, with the encapsulation of other antibiotic agent into the structure, an enhanced antibacterial effect under dual-modality could also be achieved. PMID- 27387018 TI - Multidrug-resistant Acinetobacter baumannii ventriculitis: a serious clinical challenge for neurosurgeons. PMID- 27387019 TI - High circulating osteoprotegerin levels are associated with non-zero blood groups. AB - BACKGROUND: Osteoprotegerin (OPG) and von Willebrand factor (VWF) form complex within endothelial cells and following secretion. The nature of blood group antigens strongly influences the levels of circulating VWF, but there is no available data concerning its ascendancy on OPG levels. We aimed to assess the relationship of AB0 blood groups with OPG, VWF levels (VWF: Ag) and collagen binding activity (VWF: CB) in peripheral arterial disease (PAD) patients. METHODS: Functional and laboratory parameters of 105 PAD patients and 109 controls were examined. Results of OPG, VWF: Ag, VWF: CB (ELISA-s) were analysed by comparative statistics, together with clinical data. RESULTS: OPG levels were higher in patients than in controls (4.64 ng/mL vs. 3.68 ng/mL, p < 0.001). Among patients elevation was marked in the presence of critical limb ischemia (5.19 ng/mL vs. 4.20 ng/mL, p = 0.011). The OPG in patients correlated positively with VWF: Ag and VWF: CB (r = 0.26, p = 0.008; r = 0.33, p = 0.001) and negatively with ankle-brachial pressure index (r = -0.22, p = 0.023). Furthermore, OPG was significantly elevated in non-0 blood groups compared to 0-groups both in patients and controls (4.95 ng/mL vs. 3.90 ng/mL, p = 0.012 and 4.09 ng/mL vs. 3.40 ng/mL, p = 0.002). CONCLUSIONS: OPG levels are associated to blood group phenotypes and higher in non-0 individuals. Increased OPG levels in PAD characterize disease severity. The significant correlation between OPG and VWF:CB might have functional importance in an atherothrombosis-prone biological environment. PMID- 27387020 TI - Fecal Microbiota Transplantation in Combination with Soluble Dietary Fiber for Treatment of Slow Transit Constipation: A Pilot Study. AB - BACKGROUND AND AIMS: Intestinal microbiota and soluble dietary fiber play an important role in intestinal microecology, which is closely related to gut motility. Regulating intestinal microecology comprised of fecal microbiota transplantation (FMT) or fiber supplementation is becoming a novel therapy for functional gastrointestinal disease. We launched this study to evaluate the efficacy and safety of FMT combined with fiber for slow transit constipation (STC). METHODS: We performed a study of 21 patients with STC. Participants received FMT (via nasojejunal tubes) on 3 consecutive days. After FMT, they were recommended to receive soluble dietary fiber for 4 weeks (8 g, twice daily). Rate of clinical improvement and remission, constipation-related symptoms (PAC-SYM scores), bowel movements per week, colonic transit time (CTT) and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. RESULTS: At the study end, clinical improvement and remission of constipated patients reached 66.7 and 42.9%, respectively. The patients showed an increased stool frequency from 1.7 +/- 0.5 per week to 4.8 +/- 2.1 per week (p <0.05) and an improved stool consistency after FMT combined with fiber. When compared to pre-treatment, PAC-SYM scores improved significantly from 2.0 +/- 0.4 to 1.5 +/- 0.6 after treatment (p <0.05). Meanwhile, patients showed an acceleration of colonic transit time from 81.9 +/- 9.5 to 53.5 +/- 11.2 h at week 12. During follow-up, patients felt satisfied with improved GIQLI. No serious adverse events were observed. CONCLUSION: This is a pilot study confirming that FMT combined with fiber may improve symptoms experienced by constipated patients by regulating intestinal microecology, without any serious adverse events. PMID- 27387021 TI - Evaluation of the Clinical Significance of Serum Carcinoembryonic Antigen in Patients with Resectable Gastric Adenocarcinoma. AB - BACKGROUND AND AIMS: Carcinoembryonic antigen (CEA) is the most commonly used tumor marker for gastrointestinal cancers but its value for resectable gastric adenocarcinoma (RGA) patients in areas of high GA incidence is uncertain. METHODS: We retrospectively studied 400 subjects with RGA from the Fujian Province in China, which has a high incidence of GA. Patients had surgery between January 2010 and December 2013. CEA was measured and correlated to pathology. RESULTS: High pretreatment serum CEA (>5 ng/mL) was associated with patient age (p = 0.000), tumor size (p = 0.008), and T and N stages (p = 0.002, p = 0.032, respectively), alpha fetoprotein (p = 0.014), and CA19-9 (p = 0.000). High CEA was significantly associated with poor overall survival. Overall survival in the whole group of patients was 63.8%, whereas it was only 42.9% in the high CEA group (p = 0.0001). Mean overall survival for high CEA patients was significantly shorter than patients with low CEA (36.5 +/- 2.63 months vs. 47.4 +/- 0.98 months, p = 0.000). Multivariate analysis confirmed that pretreatment serum CEA was an independent prognostic factor for increased death risk. Additionally, mean CEA in 45 high CEA patients was reduced after surgery. CONCLUSIONS: Pretreatment serum CEA may help to predict survival for patients with RGA in high GA incidence areas. PMID- 27387022 TI - Virological Determinants of Spontaneous Postpartum e Antigen Seroconversion and Surface Antigen Seroclearance in Pregnant Women Infected with Hepatitis B Virus. AB - BACKGROUND AND AIMS: We investigated the virological factors predicting spontaneous postpartum hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) seroclearance in pregnant women infected with hepatitis B virus (HBV). METHODS: We invited 419 HBV infected women whose sera had been collected during their pregnancy from August 2002-July 2004 and archived at -30 degrees C, to participate the follow-up in October 2009-March 2010. Various virological factors were determined and compared in women with or without the seroconversion and seroclearance. RESULTS: A total of 264 (63.0%) antiviral naive women participated in the follow-up with an average observation period of 6.4 years (5.4-7.4). Of 76 women who were HBeAg positive during pregnancy, 42 (55.3%) seroconverted to anti-HBe during follow-up. Compared to pregnant women with HBV DNA >=3 * 10(7) IU/mL or HBeAg >=770 S/CO, those with HBV DNA <3 * 10(7) IU/mL or HBeAg <770 S/CO had higher conversion rate, with odds ratios (OR) of 7.32 (95% confidence interval [CI], 2.00-26.78) and 5.94 (95% CI, 1.40-25.16), respectively. Thirty eight (14.4%) women cleared HBsAg; pregnant women with HBsAg levels of 100-999 and <100 IU/mL had higher HBsAg seroclearance rate with OR of 2.58 (95% CI, 1.03-6.43) and 13.33 (95% CI, 5.07-35.07), respectively, compared to those with HBsAg >1000 IU/mL. CONCLUSIONS: HBeAg-positive pregnant women with HBV DNA <3 * 10(7) IU/mL or HBeAg <770 S/CO are more likely to undergo postpartum HBeAg seroconversion. HBsAg <100 IU/mL is a strong predictor of spontaneous postpartum HBsAg seroclearance. PMID- 27387023 TI - Relationship Between Echocardiographically Evaluated Aortic Stiffness and Prolidase Activity in Aortic Tissue of Patients with Critical Coronary Artery Disease. AB - BACKGROUND AND AIMS: The aim of this study was to determine the relationship between echocardiographically evaluated aortic stiffness and prolidase activity in aortic tissue of patients with critical coronary occlusion. METHODS: Thirty six patients with coronary artery disease (CAD) scheduled for CABG and 30 control patients with no CAD proven angiographically were enrolled in this study. Plasma prolidase activities were quantified spectrophotometrically. During performance of the proximal anastomoses in the study group, a piece of aortic tissue was taken by punch and tissue prolidase activity was quantified spectrophotometrically and also evaluated pathologically by prolidase immunostaining. Eventually, the correlation of plasma prolidase activity, aortic tissue prolidase activity and aortic prolidase immunohistochemical staining with aortic stiffness was studied. RESULTS: The correlation of aortic stiffness with aortic tissue prolidase activity (rs = 0.364; p = 0.029) and aortic prolidase immunohistochemical staining (rs = 0.354; p = 0.034) was significant in the study group. However, the correlation of plasma prolidase activity with aortic stiffness was not statistically significant (rs = 0.083; p = 0.292). Linear regression analysis showed that the aortic stiffness beta index was significantly associated with aortic tissue prolidase activity (beta = 0.354; p = 0.034) and statin usage (beta = -0.334; 0.047) in the study group. Regression analysis revealed that ATPA and statin use were predictors of aortic stiffness, and API+ was found to be the predictor for ATPA (beta = 0.449; p = 0.006). CONCLUSION: Aortic tissue prolidase activity was more significant than plasma prolidase activity and aortic tissue prolidase immunohistochemical staining in the relationship with aortic stiffness in the critical CAD group. PMID- 27387024 TI - Decision-making for delivery location and quality of care among slum-dwellers: a qualitative study in Uttar Pradesh, India. AB - BACKGROUND: In 2013, the Government of India launched the National Urban Health Mission (NUHM) in order to better address the health needs of urban populations, including the nearly 100 million living in slums. Maternal and neonatal health indicators remain poor in India. The objective of this study is to highlight the experiences of women, their husbands, and mothers-in-law related to maternal health services and delivery experiences. METHODS: In total, we conducted 80 in depth interviews, including 40 with recent mothers, 20 with their husbands, and 20 with their mothers-in-law. Purposeful sampling was conducted in order to obtain differences across delivery experiences (facility vs. home), followed by their family members. RESULTS: Major factors that influence decision-making about where to seek care included household dynamics and joint-decision-making with families, financial barriers, and perceived quality of care. Women perceived that private facilities were higher quality compared to public facilities, but also more expensive. Disrespectful care, bribes in the facility, and payment challenges were common in this population. CONCLUSIONS: A number of programmatic and policy recommendations are highlighted from this study. Future endeavors should include a greater focus on health education and public programs, including educating women on how to access programs, who is eligible, and how to obtain public funds. Families need to be educated on their rights and expectations in facilities. Future programs should consider the role of husbands and mothers-in law in reproductive decision-making and support during deliveries. Triangulating information from multiple sources is important for future research efforts. PMID- 27387025 TI - MALDI-TOF MS in clinical parasitology: applications, constraints and prospects. AB - Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is currently being used for rapid and reproducible identification of bacteria, viruses and fungi in clinical microbiological laboratories. However, some studies have also reported the use of MALDI-TOF MS for identification of parasites, like Leishmania, Giardia, Cryptosporidium, Entamoeba, ticks and fleas. The present review collates all the information available on the use of this technique for parasites, in an effort to assess its applicability and the constraints for identification/diagnosis of parasites and diseases caused by them. Though MALDI-TOF MS-based identification of parasites is currently done by reference laboratories only, in future, this promising technology might surely replace/augment molecular methods in clinical parasitology laboratories. PMID- 27387026 TI - Safety evaluation of Bon-sante cleanser(r) polyherbal in male Wistar rats. AB - BACKGROUND: The potential harm of medicinal herbs has been recently observed following herbal toxicity studies after ingestion of polyherbal remedies. This was the rationale for the food and drug regulatory agency decision for thorough safety evaluation of herbal medicines. Androgenic, antipyretic, analgesic and anti-inflammatory potentials as well as chemical compositions of extracts of massularia acuminata, terminalia ivorensis, anogeissus leiocarpus and macuna pruriens respectively have been documented. Thus, Bon-sante cleanser(r) (BSC) is formulated from these medicinal plants with the intention to boost body hormones and energizes the body. Considering the wide usage of BSC, we investigated on its safety in male Wistar rats. METHODS: Thirty-two male Wistar rats weighing 201.9 +/- 7.5 g were grouped into four treatment groups of eight per group. Group I, (control) received distilled water (10 ml/kg). Groups II-IV received 250 mg/kg, 500 mg/kg and 1000 mg/kg of BSC per oral respectively. Each group was treated for sixty days. RESULTS: Acute toxicity test, in male Wistar albino mice, showed that LD50 was 600 mg/kg via i.p. while 4 g/kg was nonlethal after oral administration in mice. Hepatic and renal biomarker enzymes were unaltered in all rats. Increased in PCV (p <0.05) was observed at 500 mg/kg. BSC modulates antioxidants biomarkers following sub-chronic administration and increased serum Na(+) (p >0.05). BSC at 1000 mg/kg caused mild inflammation of the liver and heart but not kidneys histologically. CONCLUSIONS: BSC has been found to be relatively safe in Wistar rats. Although, our findings indicate that herbal therapy with BSC should be done with caution as a mild alteration in the liver and heart architectures were observed. PMID- 27387027 TI - Pre-diagnostic body mass index and weight change in relation to colorectal cancer survival among incident cases from a population-based cohort study. AB - BACKGROUND: Whether excess body weight influences colorectal cancer (CRC) survival is unclear. We studied pre-diagnostic body mass index (BMI) and weight change in relation to CRC-specific mortality among incident CRC cases within a large, Norwegian cohort. METHODS: Participants' weight was measured at health examinations up to three times between 1974 and 1988. CRC cases were identified through linkage with the Norwegian Cancer Registry. In total, 1336 men and 1180 women with a weight measurement >3 years prior to diagnosis were included in analyses. Hazard ratios (HRs) and confidence intervals (CIs) were estimated with Cox regression. RESULTS: During a mean follow-up of 5.8 years, 507 men and 432 women died from CRC. Obesity (BMI >=30 kg/m(2)) was associated with higher CRC specific mortality than normal weight (BMI 18.5-25 kg/m(2)) in men with proximal colon cancer, HR = 1.85 (95 % CI 1.08-3.16) and in women with rectal cancer, HR = 1.93 (95 % CI 1.13-3.30). Weight gain was associated with higher CRC-specific mortality in women with CRC, colon cancer, and distal colon cancer, HRs per 5 kg weight gain were 1.18 (95 % CI 1.01-1.37), 1.22 (95 % CI 1.02-1.45), and 1.40 (95 % CI 1.01-1.95), respectively. Weight gain was not significantly associated with survival in men. CONCLUSIONS: Maintaining a healthy weight may benefit CRC survival, at least in women. PMID- 27387028 TI - A comprehensive study of the genomic differentiation between temperate Dent and Flint maize. AB - BACKGROUND: Dent and Flint represent two major germplasm pools exploited in maize breeding. Several traits differentiate the two pools, like cold tolerance, early vigor, and flowering time. A comparative investigation of their genomic architecture relevant for quantitative trait expression has not been reported so far. Understanding the genomic differences between germplasm pools may contribute to a better understanding of the complementarity in heterotic patterns exploited in hybrid breeding and of mechanisms involved in adaptation to different environments. RESULTS: We perform whole-genome screens for signatures of selection specific to temperate Dent and Flint maize by comparing high-density genotyping data of 70 American and European Dent and 66 European Flint inbred lines. We find 2.2 % and 1.4 % of the genes are under selective pressure, respectively, and identify candidate genes associated with agronomic traits known to differ between the two pools. Taking flowering time as an example for the differentiation between Dent and Flint, we investigate candidate genes involved in the flowering network by phenotypic analyses in a Dent-Flint introgression library and find that the Flint haplotypes of the candidates promote earlier flowering. Within the flowering network, the majority of Flint candidates are associated with endogenous pathways in contrast to Dent candidate genes, which are mainly involved in response to environmental factors like light and photoperiod. The diversity patterns of the candidates in a unique panel of more than 900 individuals from 38 European landraces indicate a major contribution of landraces from France, Germany, and Spain to the candidate gene diversity of the Flint elite lines. CONCLUSIONS: In this study, we report the investigation of pool-specific differences between temperate Dent and Flint on a genome-wide scale. The identified candidate genes represent a promising source for the functional investigation of pool-specific haplotypes in different genetic backgrounds and for the evaluation of their potential for future crop improvement like the adaptation to specific environments. PMID- 27387029 TI - Neuroteratogenic Viruses and Lessons for Zika Virus Models. AB - The Centers for Disease Control and Prevention has confirmed that Zika virus (ZIKV) causes congenital microcephaly. ZIKV now joins five other neuroteratogenic (NT) viruses in humans and ZIKV research is in its infancy. In addition, there is only one other NT human arbovirus (Venezuelan equine encephalitis virus), which is also poorly understood. But further insight into ZIKV can be found by evaluating arboviruses in domestic animals, of which there are at least seven NT viruses, three of which have been well studied. Here we review two key anatomical structures involved in modeling transplacental NT virus transmission: the placenta and the fetal blood-brain barrier. We then survey major research findings regarding transmission of NT viruses for guidance in establishing a mouse model of Zika disease that is crucial for a better understanding of ZIKV transmission and pathogenesis. PMID- 27387030 TI - Obesity status trajectory groups among elementary school children. AB - BACKGROUND: Little is known about patterns in the transition from healthy weight to overweight or obesity during the elementary school years. This study examined whether there were distinct body mass index (BMI) trajectory groups among elementary school children, and predictors of trajectory group membership. METHODS: This is a secondary analysis of 1651 elementary school children with complete biannual longitudinal data from kindergarten to the beginning of 5(th) grade. Heights and weights were measured by trained school nurses using standard procedures at the beginning and end of each school year for 11 consecutive assessments. Group-based trajectory clustering and multinomial logit modeling were conducted. RESULTS: When using BMIz score, six trajectory groups were identified revealing substantial consistency in BMIz score across time. When using a categorical variable separating overweight/obese children (BMI >= 85%ile) from the rest, five developmental trajectories (persistently non-overweight/obese weight: 51.1 %; early-onset overweight/obese: 9.2 %; late-onset overweight/obese: 9.7 %; becoming healthy weight: 8.2 %; and chronically overweight/obese: 21.8 %) were identified. When using a categorical variable separating obese children (BMI >= 95%ile) from the rest, three trajectories (persistently non-obese: 74.1 %, becoming obese: 12.8 %; and chronically obese: 13.2 %) were identified. For both cutoffs (>= BMI percentile 85 % or 95 %), girls were more likely than boys to be classified in the persistently non-overweight and/or obese group (odds ratios (OR) ranged from 0.53 to 0.67); and Hispanic children and non-Hispanic Black children were more likely to be chronically overweight and/or obese than non Hispanic White children (OR ranged from 1.57 to 2.44). Hispanic children were also more likely to become obese (OR: 1.84) than non-Hispanic White children when >= BMI percentile 95 % was used. CONCLUSIONS: Boys, Hispanic and non-Hispanic Black children were at higher risk of being overweight or obese throughout their elementary school years, supporting the need for obesity treatment. Post kindergarten and post second grade summer months were times when some children transitioned into overweight/obesity. It will be important to identify which behavioral factors (e.g., diet, physical activity, sedentary behaviors, and/or sleep) predisposed children to becoming overweight/obese, and whether these factors differ by time (Kindergarten versus second grade). If behavioral predisposing factors could be identified early, targeted obesity prevention should be offered. PMID- 27387031 TI - Criterion validity of the activPALTM and ActiGraph for assessing children's sitting and standing time in a school classroom setting. AB - BACKGROUND: Few studies have investigated the accuracy of the ActiGraph (AG) GTX3 accelerometer for assessing children's sitting and standing time. The activPAL (aP) has an inclinometer function that enables it to distinguish between sitting/lying and standing; however, its accuracy for assessing sitting and standing in older children is unknown. This study validated the accuracy of these devices for estimating sitting and standing time in a school classroom against a criterion measure of direct observation (DO). FINDINGS: Forty children in grades 5-7 wore both devices while being video recorded during two school lessons. AG and aP data were simultaneously collected in 15-s epochs. Individual participant DO and aP data were recorded as total time spent sitting/lying, standing and stepping. AG data were converted into time spent sitting and standing using previously established cut-points. Compared with DO, the aP underestimated sitting time (mean bias = -1.9 min, 95 % LoA = -8.9 to 5.2 min) and overestimated standing time (mean bias = 1.8 min, 95% LoA = -9.6 to 13.3 min). The best performing AG cut-point across both sitting and standing (<75 counts/15 s) was more accurate than the aP, underestimating sitting time (mean bias = -0.8 min, 95 % LoA = -10.5 to 9.9 min) and standing time (mean bias = -0.4 min, 95% LoA = -9.8 to 9.1 min), but was less precise as evidenced by wider LoAs and poorer correlations with DO (sitting r = 0.86 aP vs 0.80 AG; standing r = 0.78 aP vs 0.60 AG). CONCLUSIONS: The aP demonstrated good accuracy and precision for assessing free-living sitting and standing time in classroom settings. The AG was most accurate using a cut-point of < 75 counts/15 s. Further studies should validate the monitors in settings with greater inter- and intra-individual variation in movement patterns. PMID- 27387032 TI - Improving Comfort of Patients with Ureteral Obstruction and Malignant Disease Should Be of Concern. PMID- 27387033 TI - Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report. AB - BACKGROUND: Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate. CASE PRESENTATION: We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant. CONCLUSIONS: This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis. PMID- 27387034 TI - Optical coherence tomography angiography in dural carotid-cavernous sinus fistula. AB - BACKGROUND: Recently, applications of optical coherence tomography angiography (OCTA) have been limited to the retina and posterior segment. Although early studies have described its use for other clinical applications, its role in anterior segment vasculature and optic disc imaging has been limited thus far. CASE PRESENTATION: We describe a novel clinical application of OCTA in a patient with dural carotid-cavernous sinus fistula (CCF), which was complicated by increased intra-ocular pressure (IOP). In this case report, we used the OCTA to delineate increased epsicleral venous flow in the affected eye with secondary raised IOP. Current measurements of episcleral venous pressure are either invasive or provide highly variable results, thus the OCTA may have the potential to provide a more reliable approach to assess episcleral vasculature. We also describe the use of OCTA to detect early glaucomatous nerve damage, associated with focal reductions in peripapillary retinal perfusion. CONCLUSIONS: We present an early report of using OCTA of the anterior segment to allow rapid, non invasive delineation of abnormal episcleral venous plexus secondary to dural CCF. The OCTA was also useful for detecting early reduction in peripapillary retinal perfusion, which suggests early glaucomatous optic neuropathy. This suggests that OCTA may have a role for determining risk of glaucoma in patients with CCF in future. PMID- 27387035 TI - High-Oriented Polypyrrole Nanotubes for Next-Generation Gas Sensor. AB - Highly oriented PPy nanotubes are grown by in situ vapor phase polymerization within a nanoscale template under low temperature. As-fabricated PPy nanotubes are used for gas sensing, where an ultralow detection limit (0.05 ppb) and very fast response are achieved. Such an in situ mass-productive method for synthesizing highly oriented conducting polymers may pave a new step toward next generation gas sensors. PMID- 27387036 TI - MCR-1 in multidrug-resistant and copper-tolerant clinically relevant Salmonella 1,4,[5],12:i:- and S. Rissen clones in Portugal, 2011 to 2015. AB - The mcr-1 gene was found in 11 isolates from a Portuguese Salmonella collection (n = 1,010; 58 serotypes; 2002-15) of clinical samples, foodstuff, food-animals and water. Mcr-1 has been located on different plasmids (IncX4/IncHI2) in pig associated multidrug-resistant, copper-tolerant S.1,4,[5],12:i:-/ST34 and S. Rissen/ST469 clones from human and pork products since at least 2011. Our data highlight dissemination of mcr-1 by successful resistant clones in Europe and raise questions about the efficacy of copper-based interventions to reduce colistin use. PMID- 27387037 TI - Erratum. PMID- 27387038 TI - Resistant or Sensitive: Time Is of the Essence: Response to Malek et al. PMID- 27387039 TI - Low impact of urine cultures as a diagnostic tool in patients with neutropenic fever. PMID- 27387041 TI - Can I trust in what I see? EEG evidence for a cognitive evaluation of perceptual constructs. AB - Environmental information available to our senses is incomplete and to varying degrees ambiguous. It has to be disambiguated in order to construct stable and reliable percepts. Ambiguous figures are artificial examples where perception is maximally unstable and alternates between possible interpretations. Tiny low level changes can disambiguate an ambiguous figure and thus stabilize percepts. The present study compares ERPs evoked by ambiguous stimuli and disambiguated stimulus variants across three visual categories: geometry (Necker cube), motion (stroboscopic alternative motion stimulus, SAM) and semantics (Boring's old/young woman). We found that (a) disambiguated stimulus variants cause stable percepts and evoke two huge positive ERP excursions (Cohen's effect sizes 1-2), (b) the amplitudes of these ERP effects are inversely related to the degree of stimulus ambiguity, and (c) this pattern of results is consistent across all three tested visual categories. This generality across visual categories points to mechanisms at a very abstract (cognitive) level of processing. We discuss our results in the context of a high-level Bayesian inference unit that evaluates the reliability of perceptual processing results, given a priori incomplete, ambiguous sensory information. The ERP components may reflect the outcome of this reliability estimation. PMID- 27387040 TI - Minireview: Insights Into the Structural and Molecular Consequences of the TSH beta Mutation C105Vfs114X. AB - Naturally occurring thyrotropin (TSH) mutations are rare, which is also the case for the homologous heterodimeric glycoprotein hormones (GPHs) follitropin (FSH), lutropin (LH), and choriogonadotropin (CG). Patients with TSH-inactivating mutations present with central congenital hypothyroidism. Here, we summarize insights into the most frequent loss-of-function beta-subunit of TSH mutation C105Vfs114X, which is associated with isolated TSH deficiency. This review will address the following question. What is currently known on the molecular background of this TSH variant on a protein level? It has not yet been clarified how C105Vfs114X causes early symptoms in affected patients, which are comparably severe to those observed in newborns lacking any functional thyroid tissue (athyreosis). To better understand the mechanisms of this mutant, we have summarized published reports and complemented this information with a structural perspective on GPHs. By including the ancestral TSH receptor agonist thyrostimulin and pathogenic mutations reported for FSH, LH, and choriogonadotropin in the analysis, insightful structure function and evolutionary restrictions become apparent. However, comparisons of immunogenicity and bioactivity of different GPH variants is hindered by a lack of consensus for functional analysis and the diversity of used GPH assays. Accordingly, relevant gaps of knowledge concerning details of GPH mutation-related effects are identified and highlighted in this review. These issues are of general importance as several previous and recent studies point towards the high impact of GPH variants in differential signaling regulation at GPH receptors (GPHRs), both endogenously and under diseased conditions. Further improvement in this area is of decisive importance for the development of novel targeted therapies. PMID- 27387042 TI - Preexposure Prophylaxis and Patient Centeredness: A Call for Holistically Protecting and Promoting the Health of Gay Men. AB - Preexposure prophylaxis has transformed HIV prevention, becoming widespread in communities of gay and bisexual men in the developed world in a short time. There is a broad concern that preexposure prophylaxis will discourage condom use among gay men (i.e., "risk compensation"). This commentary argues for broadening the focus on gay men's health beyond sexual health to address the holistic health and well-being of gay men. Gay men may benefit from being offered candid, nonjudgmental health promotion/HIV prevention messages not requiring condom use for anal sex. Lessons can be drawn from the family planning movement, which has undergone a similar shift in focus. The principle of patient centeredness supports such a shift in gay men's health toward the goal of providing men with the knowledge to evaluate various prevention approaches according to the specifics of their life circumstances and health needs. Bringing more nuance to discussions of sexual risk and sexual pleasure could facilitate more universally healthy attitudes regarding sex among gay men, in turn enabling healthier decisions more compatible with men's own values and preferences. PMID- 27387043 TI - [Evaluation of knowledge in the composition of fluids of resuscitation of the personnel medical intraining]. PMID- 27387044 TI - [Implementation of a best practice guideline for the prevention of falls: Perception among hospitalized patients and its caregivers]. AB - OBJECTIVE: To analyze the influence that the implementation of a fall prevention Best Practice Guideline (BPG) could have on the perception of patients and their caregivers about the utility of the activities implemented, about the care provided during admission and the adherence (the level of follow-up) to the recommendations received at discharge. MATERIAL AND METHOD: Design. Quasi experimental study. Patients >65 years admitted>=48h to the Medical Area of the General Hospital of Albacete. SAMPLE: 104 subjects (consecutive sampling January March 2013). Experimental group (EG). Patients admitted to BPG implementation units. Control group (CG). Usual care units. VARIABLES: Sociodemographic characteristics; previous and during admission falls, cognitive status (Pfeiffer); independence in daily life activities (ADLs); satisfaction with care and information provided, utility perceived, adherence to recommendations at discharge. DATA SOURCES: Interview and clinical history. Statistical analysis (SPSS 15.0). Descriptive and bivariant. Relative Risk. CI95%. RESULTS: 104 patients, EG 46.2% (48) and CG 53.8% (56). Women 51.9%, average age 79.9 years (s.d.=7.8). Pfeiffer 4,3 (s.d.=3.7). Previous falls 31.1%. In process, 1 fall in each group. There were statistically significant differences between EG/CG: age, cognitive status and independence in ADLs. In the EG was higher the percentage of perception about the usefulness of the recommendations to prevent falls (P<.001), greater adherence to them (P=0.0002), and to be very or quite satisfied with the information (P<.00004) and care received (P=.002). CONCLUSION: To implement recommendations according to an Evidence-based BPG to prevent falls in older people has shown, in users and caregivers, greater satisfaction, better perception of its usefulness and greater adherence to the recommendations. PMID- 27387045 TI - Combination therapy in relapsed or refractory chronic immune thrombocytopenia: a case report and literature review. AB - WHAT IS KNOWN AND OBJECTIVE: Immune destruction and decreased platelet production are major components of immune thrombocytopenia (ITP) pathogenesis. The aim of this study was to critically evaluate the role of combination therapy in relapsed/refractory ITP and the concept of medication tapering/discontinuation. COMMENT: Although a number of combination regimens have been reported, little is published on combining immunosuppression with thrombopoietin receptor agonists (TPO-RAs). We report a case of refractory ITP successfully treated with combination immunosuppression added to eltrombopag. An aggressive combination approach resulted in complete remission and allowed for stepwise drug tapering. WHAT IS NEW AND CONCLUSION: Combination immunosuppression can potentiate the effect of TPO-RAs. This mechanistically reasonable strategy could result in a more rapid response than the more popular, sequential, single-agent strategy. Stepwise tapering can be successfully implemented. Comparing sequential single agent therapy with early combination approach warrants a more extensive study. PMID- 27387047 TI - Mandarin Lexical Tone Acquisition in Cochlear Implant Users With Prelingual Deafness: A Review. AB - PURPOSE: The purpose of this review article is to synthesize evidence from the fields of developmental linguistics and cochlear implant technology relevant to the production and perception of Mandarin lexical tone in cochlear implant users with prelingual deafness. The aim of this review was to identify potential factors that determine outcomes for tonal-language speaking cochlear implant users and possible directions for further research. METHOD: A computerized database search of MEDLINE, CINAHL, Academic Search Premier, Web of Science, and Google Scholar was undertaken in June and July 2014. Search terms used were lexical tone AND tonal language, speech development AND/OR speech production AND/OR speech perception AND cochlear implants, and pitch perception AND cochlear implants, anywhere in the title or abstract. CONCLUSION: Despite the demonstrated limitations of pitch perception in cochlear implant users, there is some evidence that typical production and perception of lexical tone is possible by cochlear implant users with prelingual deafness. Further studies are required to determine the factors that contribute to better outcomes to inform rehabilitation processes for cochlear implant users in tonal-language environments. PMID- 27387046 TI - Micronutrients and Leptospirosis: A Review of the Current Evidence. AB - BACKGROUND: Leptospirosis is one of the most widespread zoonoses and represents a major threat to human health. Due to the high burden of disease, limitations in diagnostics, and limited coverage and availability of effective human and veterinary vaccines, leptospirosis remains an important neglected zoonotic disease. Improved surveillance and identification of modifiable risk factors for leptospirosis are urgently needed to inform preventive interventions and reduce the risk and severity of Leptospira infection. METHODOLOGY/PRINCIPAL FINDINGS: This review was conducted to examine the evidence that links micronutrient status and Leptospira infection. A total of 56 studies were included in this review: 28 in vitro, 17 animal, and 11 observational human studies. Findings indicated that Leptospira infection is associated with higher iron and calcium concentrations and hypomagnesemia. CONCLUSIONS/SIGNIFICANCE: Few prospective studies and no randomized trials have been conducted to date to examine the potential role of micronutrients in Leptospira infection. The limited literature in this area constrains our ability to make specific recommendations; however, the roles of iron, calcium, and magnesium in leptospirosis represent important areas for future research. The role of micronutrients in leptospirosis risk and severity needs to be elucidated in larger prospective human studies to inform public health interventions. PMID- 27387048 TI - Association of Biomarkers of Inflammation and Endothelial Dysfunction with Fasting and Postload Glucose Metabolism: A Population-Based Prospective Cohort Study Among Inner Mongolians in China. AB - OBJECTIVE: To examine the associations between elevated levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E selectin (sE-selectin) with fasting and 2-hour postload glucometabolic status among Inner Mongolians in China. METHODS: Based on a cross-sectional survey of patients during 2003, 2260 participants were reinvestigated between 2013 and 2014. We categorized the participants into 3 subgroups according to fasting and postload glucose levels, respectively. The associations between biomarkers of inflammation and endothelial dysfunction and deterioration of fasting and postload glucometabolic status were examined by ordinal logistic regression analysis. RESULTS: We found 142 and 49 persons who had impaired fasting glucose (IFG) levels and type 2 diabetes in the fasting state and 335 and 50 persons who had impaired glucose tolerance (IGT) and type 2 diabetes in the postload state. After multivariable adjustment, elevated CRP and sICAM-1 levels were associated with deterioration of fasting glucometabolic status from normal fasting glucose to IFG and type 2 diabetes (odds ratio [OR] 1.73 [95% CI 1.18 to 2.54] for elevated CRP levels, OR 1.86 [95% CI 1.30 to 2.66] for elevated sICAM-1 levels). Elevated sE-selectin levels were associated with deterioration of postload glucometabolic status from normal glucose tolerance to IGT and type 2 diabetes (OR 1.34 [95% CI 1.01 to 1.77]) in the multivariable-adjusted model. CONCLUSIONS: Biomarkers of inflammation and endothelial dysfunction were separately associated with fasting and postload glucose metabolism among Inner Mongolians. PMID- 27387049 TI - Alcohol consumption after health deterioration in older adults: a mixed-methods study. AB - OBJECTIVE: To examine if and how older adults modify their drinking after health deterioration, and the factors that motivate changing or maintaining stable drinking behaviour. STUDY DESIGN: Explanatory follow-up mixed-methods research. METHODS: The association between health deterioration and changes in alcohol consumption was examined using secondary data from the English Longitudinal Study of Ageing, a biennial prospective cohort study of a random sample of adults aged 50 years and older living in England. Data were collected through a personal interview and self-completion questionnaire across three waves between 2004 and 2009. The sample size (response rate) across the three waves was 8781 (49.9%), 7168 (40.3%) and 6623 (37.3%). The Chi-squared test was used to examine associations between diagnosis with a long-term condition or a worsening of self rated health (e.g. from good to fair or fair to poor) and changes in drinking frequency (e.g. everyday, 5-6 days per week, etc.) and volume (ethanol consumed on a drinking day) between successive waves. In-depth interviews with 19 older adults recently diagnosed with a long-term condition were used to explore the factors that influenced change or maintenance in alcohol consumption over time. A purposive sampling strategy was used to recruit a diverse sample of current and former drinkers from voluntary and community organizations in the north of England. An inductive approach was used to analyze the data, facilitating the development of an a posteriori framework for understanding drinking change. RESULTS: There was no significant relationship between health deterioration and changes in drinking volume over time. There was however a significant association between health deterioration and changes in drinking frequency between successive waves (chi2 = 15.24, P < 0.001 and chi2 = 17.28, P < 0.001). For example, of participants reporting health deterioration between the first two waves, 47.6% had stable drinking frequency, 23.4% increased their drinking frequency and 29% reported decreased drinking frequency. In comparison, of participants reporting no health deterioration, 52.7% reported stable frequency, 20.8% increased frequency and 26.4% decreased frequency. In qualitative interviews, older adults described a wide range of factors that influence changes in drinking behaviour: knowledge gained from talking to healthcare professionals, online and in the media; tangible negative experiences that were attributed to drinking; mood and emotions (e.g. joy); the cost of alcohol; pub closures; and changes in social roles and activities. Health was just one part of a complex mix of factors that influenced drinking among older adults. CONCLUSION: Patterns of drinking change after health deterioration in older adults are diverse, including stable, increasing and decreasing alcohol consumption over time. Although health motivations to change drinking influence behaviour in some older adults, social and financial motivations to drink are also important in later life and thus a holistic approach is required to influence behaviour. PMID- 27387050 TI - Sustainability of the Health System: Beyond Cost-effectiveness Analyses. Response. PMID- 27387051 TI - Sustainability of the Health System: Beyond Cost-effectiveness Analyses. PMID- 27387052 TI - Systemic Thrombolysis for High-risk Pulmonary Embolism Versus Percutaneous Transcatheter Treatment. PMID- 27387053 TI - Pseudobradycardia-dependent Left Anterior Fascicular Block. A Case Report. PMID- 27387054 TI - Systemic Thrombolysis for High-risk Pulmonary Embolism Versus Percutaneous Transcatheter Treatment. Response. PMID- 27387055 TI - Microbial platform technology for recombinant antibody fragment production: A review. AB - Recombinant antibody fragments are being used for the last few years as an important therapeutic protein to cure various critical and life threatening human diseases. Several expression platforms now days employed for the production of these recombinant fragments, out of which bacterial system has emerged a promising host for higher expression. Since, a small antibody fragment unlike full antibody does not require human-like post-translational modification therefore it is potentially expressed in prokaryotic production system. Recently, small antibody fragments such as scFvs (single-chain variable fragments) and Fabs (antibody fragments) which does not require glycosylation are successfully produced in bacteria and have commercially launched for therapeutic use as these fragments shows better tissue penetration and less immunogenic to human body compared to full-size antibody. Recently developed Wacker's ESETEC secretion technology is an efficient technology for the expression and secretion of the antibody fragment (Fab) exceeded up to 4.0 g/L while scFv up to 3.5 g/L into the fermentation broth. The Pfenex system and pOP prokaryotic expression vector are another platform used for the considerably good amount of antibody fragment production successfully. In this review, we summarize the recent progress on various expression platforms and cloning approaches for the production of different forms of antibody fragments in E. coli. PMID- 27387056 TI - An ultrasensitive assay format for detecting ULK1 inhibition by monitoring the phosphorylation status of Atg13. AB - A new technology from Quanterix called SiMoA (single molecule array) which employs a fully automated system capable of ultrasensitive sandwich based ELISA detection was explored. Our studies focused upon the inhibition of the autophagy initiating kinase ULK1 by measuring the both total Atg13 and the phosphorylation of Atg13(pSer(318)) from control and following compound treatment in either overexpressing or wild type tissue culture samples. The results show linear protein concentration dependence over two orders of magnitude and provide an assay window of 8- to 100-fold signal to background for inhibition of phosphorylation for both wild type and overexpressed samples, respectively. Moreover, overexpressed samples displayed 17-fold pSer(318)-Atg13 above wild type levels of with no apparent differences in compound potency. Lastly, the inhibition of ULK1 from mouse derived wild type xenografts also demonstrated loss of pSer(318)-Atg13 upon ULK1 inhibitor treatment that compared favorably to Western blot. These results show that the SiMoA technology can detect quantitatively low levels of endogenous biomarkers with the ability to detect the loss of pSer(318)-Atg13 upon ULK1 inhibition. PMID- 27387057 TI - Mono-sulfonated tetrazolium salt based NAD(P)H detection reagents suitable for dehydrogenase and real-time cell viability assays. AB - Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and is important for several biological processes. For GDH inhibitor screening, we developed a novel mono-sulfonated tetrazolium salt (EZMTT), which can be synthesized using H2O2 oxidation and purified easily on silica gel in large quantities. The EZMTT detection method showed linear dose responses to NAD(P)H, dehydrogenase concentration and cell numbers. In E. coli GDH assay, the EZMTT method showed excellent assay reproducibility with a Z factor of 0.9 and caused no false positives in the presence of antioxidants (such as BME). Using the EZMTT formazan-NAD(P)H system, we showed that EGCG is a potent E. coli GDH inhibitor (IC50 45 nM) and identified that Ebselen, a multifunctional thioredoxin reductase inhibitor, inactivated E. coli GDH (IC50 213 nM). In cell-based assays at 0.5 mM tetrazolium concentration, EZMTT showed essentially no toxicity after a 3-day incubation, whereas 40% of inhibition was observed for WST-8. In conclusion, EZMTT is a novel tetrazolium salt which provides improved features that are suitable for dehydrogenases and real-time cell-based high-throughput screening (HTS). PMID- 27387058 TI - The SAPAS, Personality Traits, and Personality Disorder. AB - Many argue that current categorical personality disorder (PD) classification systems should be more dimensional and consider personality traits. The present study examined whether a brief PD screening tool, the Standardized Assessment of Personality: Abbreviated Scale (SAPAS) primarily screened for traits of low emotional stability, low extraversion, and low agreeableness, rather than PD per se. A general community sample (n = 237) completed the SAPAS, a personality trait measure, and the International Personality Disorder Examination (IPDE) screening questionnaire. Regressions showed that the SAPAS provided substantial incremental validity over personality trait scores in predicting total IPDE scores, indicating that the SAPAS captures variance unique to PD, rather than just extremes of general disposition. The SAPAS is an empirically valid rapid PD screen for nonclinical populations, correctly identifying 78% of individuals who screen positively for PD on the IPDE. However, the SAPAS was not effective for screening antisocial PD, limiting its utility in forensic settings. PMID- 27387059 TI - Negative Affectivity and Effortful Control in Mothers With Borderline Personality Disorder and in Their Young Children. AB - Research has examined temperament in individuals with borderline personality disorder (BPD) but not in their offspring, despite offspring's risk of developing BPD and the importance of temperament in the etiology of BPD. We recruited a low socioeconomic sample of 36 mothers with BPD and their children ages 4 through 7, and 34 normative comparisons. Replicating prior studies, mothers with BPD reported themselves as having more negative affectivity (frustration, fear) and less effortful control (inhibitory control, attentional control, activation control) than did comparisons. Mothers with BPD also reported that their offspring had more negative affectivity (anger/frustration, fear) and less effortful control (inhibitory control, attentional focusing) than did comparisons. We were concerned about potential bias and shared method variance. We therefore provided validity support for mothers' ratings of their children with teacher ratings of child behavior and child self-report via their story-stem completion narratives. We discuss children's temperamental vulnerability versus differential susceptibility to the environment. PMID- 27387060 TI - A Meta-analysis on the Association Between Emotional Awareness and Borderline Personality Pathology. AB - Theories on borderline personality pathology (BPP) suggest that characteristic emotional dysregulation is due to low levels of emotional awareness or alexithymia. This study is the first meta-analysis to systematically review and analyze the evidence. A systematic search of the literature was performed using PsycInfo, Web of Science/MEDLINE, and Scopus. The term "borderline personality disorder" was searched for in conjunction with "emotional awareness," "emotional self-awareness," "emotion recognition," "alexithymia," "emotional processing," "emotional granularity," "emotional intelligence," or "emotion regulation." All references in the included studies were reviewed for additional relevant articles. Thirty-nine studies were then evaluated in a random effects meta analysis to assess the association between BPP and emotional awareness. An overall moderate positive association between BPP and emotional awareness was significant (r = 0.359; 95% CI [0.283, 0.431]; Z = 8.678; p < 0.001) along with high heterogeneity (Q(38) = 456.7; p < .001; I2 = 91.7%). Studies comparing borderline personality disorder to healthy controls yielded a strong association (r = 0.518; 95% CI [0.411, 0.611]). No significant difference was found between studies using instruments for emotional awareness and those using alexithymia instruments. The strongest associations with regard to aspects of alexithymia were found for difficulties in identifying and describing emotions rather than externally oriented thinking. The results corroborate a moderate relationship between low emotional awareness and BPP. However, the mono-method self-report used in almost all studies is found problematic and precludes drawing definite conclusions. Since leading psychotherapeutic treatments strongly focus on increasing emotional awareness, future research should address this issue and further examine to what extent low levels of emotional awareness, particularly alexithymia, can be treated. PMID- 27387061 TI - Transcriptional Engineering of Microalgae: Prospects for High-Value Chemicals. AB - Microalgae are diverse microorganisms that are of interest as novel sources of metabolites for various industrial, nutritional, and pharmaceutical applications. Recent studies have demonstrated transcriptional engineering of some metabolic pathways. We propose here that transcriptional engineering could be a viable means to manipulate the biosynthesis of specific high-value metabolic products. PMID- 27387062 TI - Pre-discharge defibrillation testing: Is it still justified? AB - BACKGROUND: An implantable cardioverter-defibrillator (ICD) is routinely used to prevent sudden cardiac death. Since the introduction of that device into clinical practice, a defibrillation test (the so-called pre-discharge test [PDT]) has been an inseparable part of the ICD implantation procedure. Recently, the usefulness of PDT has been called into question. METHODS: The aim of this research was to analyze ICD tests performed within two time periods: in years 1995-2001 (period I) and 2007-2010 (period II), in order to compare the results of tests and solutions to all the problems with ICD systems revealed by means of PDT. RESULTS: During period I, 193 tests were performed, among which the ICD system malfunction was observed in 16 cases. Those included: sensing issues, specifically R-wave undersensing during ventricular fibrillation (VF) (7 patients) and T-wave oversensing (4 patients), as well as high defibrillation threshold (DFT) (2 patients) and ICD-pacemaker interaction (3 patients). During period II, among 561 tests, system malfunction was observed in 15 cases. In 1 patient it was VF undersensing, and in the remaining 14 it was high DFT. All the above problems were solved by means of appropriate ICD reprogramming, repositioning of the endocardial defibrillation lead or implantation of an additional subcutaneous defibrillation lead. CONCLUSIONS: Contemporary ICD technical solutions, compared to older systems, in most cases allow to avoid sensing problems. The key rationale behind ICD testing is the ability to confirm the efficacy of high voltage therapy. Despite the increasing maximal defibrillation out-put of devices, and all possible adjustments to the characteristics of the impulse, there is still a group of patients that require additional procedures to ensure the appropriate defibrillation efficacy. PMID- 27387063 TI - Assessment of cardiac autonomic functions by heart rate recovery indices in patients with myocardial bridge. AB - BACKGROUND: Heart rate (HR) recovery (HRR) reflects autonomic activity and predicts cardiovascular events. The aim of this study was to assess HRR in patients with myocardial bridge (MB). METHODS: Medical recordings of 93 patients with MB and appropriate age, compared to 78 sex-matched healthy subjects were analyzed. MB was diagnosed via coronary computed tomography angiography after a positive exercise stress test (EST). HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2) and 3rd (HRR3) minute HR from the maximal HR during EST. RESULTS: HRR1 (30.2 +/- 13.3 bpm vs. 35.8 +/- 10.4 bpm, p = 0.001) and HRR2 (52.3 +/- 13.3 bpm vs. 57.1 +/- 11.6 bpm, p = 0.013) were lower in patients with MB. In addition, HRR1 was lower in patients with left anterior descending (LAD) MB than non-LAD MB (28.5 +/- 13.2 vs. 37.1 +/- 11.4, p = 0.013). Presence of MB, deep MB, LAD MB and multi-vessel MB were predictors of HRR1 (p < 0.01 for all). In a multivariate analysis, LAD MB was the only significant independent predictor of HRR1 (b = -8.524, p = 0.009). CONCLUSIONS: Patients with MB have impairment in HRR indices which is more pronounced among patients with LAD MB. Cardiac autonomic dysfunction in MB might be due to recurrent myocardial ischemia. PMID- 27387065 TI - Carbonic anhydrase inhibitors: a review on the progress of patent literature (2011-2016). AB - INTRODUCTION: A large area of carbonic anhydrase (CA) research focuses on the inhibition of human CA IX and CA XII, as these isoforms have been designated as biomarkers and therapeutic targets for various cancer types. AREAS COVERED: Recently, the majority of CA inhibitor (CAI) patents cover compound design, synthesis, and delivery methods for the treatment of glaucoma and cancer. The analysis of included patents highlights the need for isoform specific inhibitors. This review covers the patents of medically relevant carbonic anhydrase inhibitors between 2011-2016. EXPERT OPINION: The improvement of structure-based drug design methods and access to the crystal structures of human CA isoforms have improved inhibitor development. This progress can be observed in relation to the selective inhibition of CA IX for cancer treatments, with one inhibitor in clinical trials. However, the design of nonclassical CAIs is essential to further improve isoform specificity and prevent sulfur allergies. PMID- 27387066 TI - Corrigendum. PMID- 27387064 TI - Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNgamma-Like Response. AB - The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNgamma. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNgamma-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNgamma-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication. PMID- 27387067 TI - Cellular infiltrates in skin and sural nerve of patients with polyneuropathies. AB - INTRODUCTION: The aim of this study was to determine the diagnostic usefulness of skin punch biopsies with emphasis on visualization and quantification of T-cells and macrophages in patients with polyneuropathies. METHODS: We quantified inflammatory cells in skin samples (lower leg, upper thigh) in 187 patients and compared data with counts in their sural nerve biopsies and with skin biopsies from 32 healthy volunteers. RESULTS: Vessel-bound T-cells and macrophages were increased in proximal and distal skin samples of neuropathy patients compared with controls (P < 0.001 in both). Patients with vasculitic neuropathy had increased T-cell and macrophage counts in distal skin compared with controls (P < 0.01; for scattered macrophages/mm2 diagnostic sensitivity 71% and specificity 79%). In patients with vasculitic neuropathy, distal skin perivascular inflammatory cell counts also correlated with those in sural nerve biopsies (P < 0.001). CONCLUSION: Neuropathy per se may lead to skin inflammation. In cases of possible vasculitic neuropathy, skin biopsy may be an additional tool to support the diagnosis. Muscle Nerve 55: 884-893, 2017. PMID- 27387068 TI - Is Localized Scleroderma Caused by Borrelia burgdorferi? AB - Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi-the agent of Lyme disease-is suggested to be one of the possible etiological factors of localized scleroderma. However, among scientists, this hypothesis is quite controversial. We have conducted investigations of the level of IgM and IgG class antibodies to B. burgdorferi in the serum of patients with localized scleroderma. To rationally substantiate the role of B. burgdorferi in the occurrence of localized scleroderma, thirty-two patients with localized scleroderma treated at an in-patient department were examined. The level of anti Borrelia antibodies was determined in ELISA. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p < 0.01). Positive levels of anti-Borrelia antibodies in patients with localized scleroderma confirm the borreliosis nature of the disease, requiring conduction of complex antimicrobial treatment. PMID- 27387069 TI - Stoichiometric modelling of assimilatory and dissimilatory biomass utilisation in a microbial community. AB - Assimilatory and dissimilatory utilisation of autotroph biomass by heterotrophs is a fundamental mechanism for the transfer of nutrients and energy across trophic levels. Metagenome data from a tractable, thermoacidophilic microbial community in Yellowstone National Park was used to build an in silico model to study heterotrophic utilisation of autotroph biomass using elementary flux mode analysis and flux balance analysis. Assimilatory and dissimilatory biomass utilisation was investigated using 29 forms of biomass-derived dissolved organic carbon (DOC) including individual monomer pools, individual macromolecular pools and aggregate biomass. The simulations identified ecologically competitive strategies for utilizing DOC under conditions of varying electron donor, electron acceptor or enzyme limitation. The simulated growth environment affected which form of DOC was the most competitive use of nutrients; for instance, oxygen limitation favoured utilisation of less reduced and fermentable DOC while carbon limited environments favoured more reduced DOC. Additionally, metabolism was studied considering two encompassing metabolic strategies: simultaneous versus sequential use of DOC. Results of this study bound the transfer of nutrients and energy through microbial food webs, providing a quantitative foundation relevant to most microbial ecosystems. PMID- 27387071 TI - Comparative efficacy of a simplified handwashing program for improvement in hand hygiene and reduction of school absenteeism among children with intellectual disability. AB - BACKGROUND: Infectious diseases are common among schoolchildren as a result of their poor hand hygiene, especially in those who have developmental disabilities. METHODS: A quasi-experimental study using a pre- to post-test design with a control group was used to test the feasibility and sustainability of simplified 5 step handwashing techniques to measure the hand hygiene outcome for students with mild intellectual disability. Sickness-related school absenteeism was compared. RESULTS: The intervention group experienced a significant increase in the rating of their handwashing quality in both hands from pre- to post-test: left dorsum (+1.05, P < .001); right dorsum (+1.00, P < .001); left palm (+0.98, P < .001); and right palm (+1.09, P < .001). The pre- to post-test difference in the intervention group (+1.03, P < .001) was significantly greater than the difference in the control group (+0.34, P = .001). There were no differences between the post-test and the sustainability assessment in the intervention group. The intervention school experienced a significantly lower absenteeism rate (0.0167) than the control group in the same year (0.028, P = .04).Students in this study showed better performance in simplified handwashing techniques and experienced lower absenteeism than those using usual practice in special education school settings. CONCLUSION: The simplified 5-step hand hygiene technique has been proven effective in reducing the spread of infectious diseases. PMID- 27387072 TI - Principles of Tendon Transfer. AB - Tendon transfers provide a substitute, either temporary or permanent, when function is lost due to neurologic injury in stroke, cerebral palsy or central nervous system lesions, peripheral nerve injuries, or injuries to the musculotendinous unit itself. This article reviews the basic principles of tendon transfer, which are important when planning surgery and essential for an optimal outcome. In addition, concepts for coapting the tendons during surgery and general principles to be followed during the rehabilitation process are discussed. PMID- 27387073 TI - Biomechanics of Tendon Transfers. AB - The transfer of tendons in the upper extremity is a powerful technique to restore function to a partially paralyzed hand. The biomechanical principles of muscle tension and tendon excursion dictate motor function both in the native as well as transferred states. Appropriately tensioning transferred tendons to maximize the function of the associated muscle remains an area of focused research. Newer methods of tendon coaptation have proven similar in strength to the standard Pulvertaft weave, affording more options to the surgeon. PMID- 27387074 TI - Restoration of Shoulder Function. AB - Restoration of shoulder function in patients with brachial plexus injury can be challenging. Initial reported efforts were focused on stabilizing the shoulder, improving inferior subluxation and restoring abduction and flexion of the joint. Recent advancements and improved understanding of coordinated shoulder motion and the biomechanical properties of the muscles around the shoulder applicable to tendon transfer have expanded available surgical options to improve shoulder function, specifically external rotation. Despite the advances in reconstructive options, brachial plexus injury remains a serious problem that requires complex surgical solutions, prolonged recovery, and acceptance of functional loss. PMID- 27387075 TI - Restoration of Elbow Flexion. AB - Active elbow flexion is required to position the hand in space, and loss of this function is debilitating. Nerve transfers or nerve grafts to restore elbow flexion may be options when the target muscle is viable, but in delayed reconstruction when the biceps and brachialis are atrophied or damaged, muscle transfer options should be considered. Muscle transfer options are discussed with attention to the advantages and disadvantages of each transfer option. PMID- 27387076 TI - Radial Nerve Tendon Transfers. AB - Radial nerve palsy typically occurs as a result of trauma or iatrogenic injury and leads to the loss of wrist extension, finger extension, thumb extension, and a reduction in grip strength. In the absence of nerve recovery, reconstruction of motor function involves tendon transfer surgery. The most common donor tendons include the pronator teres, wrist flexors, and finger flexors. The type of tendon transfer is classified based on the donor for the extensor digitorum communis. Good outcomes have been reported for most methods of radial nerve tendon transfers as is typical for positional tendon transfers not requiring significant power. PMID- 27387077 TI - High Median Nerve Injuries. AB - The median nerve serves a crucial role in extrinsic and intrinsic motor and sensory function to the radial half of the hand. High median nerve injuries, defined as injuries proximal to the anterior interosseous nerve origin, therefore typically result in significant functional loss prompting aggressive surgical management. Even with appropriate recognition and contemporary nerve reconstruction, however, motor and sensory recovery may be inadequate. With isolated persistent high median nerve palsies, a variety of available tendon transfers can improve key motor functions and salvage acceptable use of the hand. PMID- 27387078 TI - Low Median Nerve Transfers (Opponensplasty). AB - Opposition is the placement of the thumb opposite the fingers into a position from which it can work. This motion requires thumb palmar abduction, flexion, and pronation, which are provided by the abductor pollicis brevis, flexor pollicis brevis (FPB), and opponens pollicis. In the setting of a median nerve palsy, this function is typically lost, although anatomic variations and the dual innervation of the FPB may prevent complete loss at times. There are multiple well described and accepted tendon transfers to restore opposition, none of which have been proven to be superior to the others. PMID- 27387079 TI - A Comprehensive Guide on Restoring Grasp Using Tendon Transfer Procedures for Ulnar Nerve Palsy. AB - Ulnar nerve paralysis results in classic stigmata, including weakness of grasp and pinch, poorly coordinated flexion, and clawing of digits. Restoration of grasp is a key portion of the reconstructive efforts after loss of ulnar nerve function. Improving flexion at the metacarpophalangeal joint can be done by static and dynamic means, although only the latter can improve interphalangeal extension. Deformity and digital posture are more predictably corrected with surgical intervention. Loss of strength from intrinsic muscle paralysis cannot be fully restored with tendon transfer procedures. Preoperative patient education is paramount to success if realistic expectations are to be met. PMID- 27387080 TI - Ulnar Nerve Tendon Transfers for Pinch. AB - Power and tip pinch are an integral part of intrinsic hand function that can be significantly compromised with dysfunction of the ulnar nerve. Loss of power pinch is one component that can significantly affect an individual's ability to perform simple daily tasks. Tip pinch is less affected, as this task has significant contributions from the median nerve. To restore power pinch, the primary focus must be on restoring the action of the adductor pollicis primarily, and if indicated the first dorsal interosseous muscle and flexor pollicis brevis. PMID- 27387081 TI - Tendon Transfers for Combined Peripheral Nerve Injuries. AB - Combined peripheral nerve injuries present a unique set of challenges to the hand surgeon when considering tendon transfers. They are often associated with severe soft tissue trauma, including lacerations to remaining innervated muscles and tendons, significant scar formation, and substantial sensory loss. In the case of combined nerve injuries, there are typically fewer options for tendon transfers due to fewer tendons of shared function that are expendable as well as associated injuries to tendon or muscle bellies. As such, careful preoperative planning must be performed to make the most of remaining muscle tendon units. PMID- 27387082 TI - Tendon Transfers for Tetraplegia. AB - It is estimated that 65% to 75% of patients with cervical spinal cord injuries could benefit from upper extremity tendon transfer surgery. The goals of surgery are to restore elbow extension, as well as hand pinch, grasp, and release. Patients who have defined goals, actively participate in therapy, and understand expected outcomes, appear to have the highest satisfaction following tendon transfer procedures. PMID- 27387083 TI - Free Flap Functional Muscle Transfers. AB - Free functional muscle transfers remain a powerful reconstructive tool to restore upper extremity function when other options such as tendon or nerve transfers are not available. This reconstructive technique is commonly used for patients following trauma, ischemic contractures, and brachial plexopathies. Variable outcomes have been reported following free functional muscle transfers that are related to motor nerve availability and reinnervation. This article highlights considerations around donor motor nerve selection, dissection, and use of the gracilis muscle, and the surgical approach to performing a free functional muscle transfer to restore elbow flexion and/or digit flexion. PMID- 27387084 TI - Tendon Transfers in the Rheumatoid Hand for Reconstruction. AB - Long-standing rheumatoid arthritis can result in spontaneous tendon rupture caused by attrition of the tendons. Ruptures of the ulnar-sided extensor tendons, flexor pollicis longus, and the flexor digitorum profundus can be seen. Primary repair of these tendon ruptures is frequently not possible because of delayed presentation and tendon damage by the disease process. Tendon transfers are the preferred method of treatment in patients with rheumatoid arthritis. At surgery, it is critical to address the underlying cause of rupture to prevent future tendon ruptures. Rates of tendon rupture may decrease due to improved medications for rheumatoid arthritis. PMID- 27387085 TI - Tendon Transfers for the Hypoplastic Thumb. AB - Thumb hypoplasia is a component of radial longitudinal deficiency. The severity of hypoplasia can range from a slightly smaller thumb to a complete absence. Types II and IIIA hypoplastic thumbs are candidates for reconstruction to improve function, stability, and strength. There are 2 commonly used tendon transfers that can augment thumb opposition strength: the Huber abductor digiti minimi muscle transfer and the flexor digitorum superficialis opposition transfer. Both transfers use ulnar-sided structures to augment the thenar musculature. The Huber opposition transfer increases thenar bulk, but does not provide additional tissue for metacarpophalangeal stability. PMID- 27387086 TI - Cerebral Palsy Tendon Transfers: Flexor Carpi Ulnaris to Extensor Carpi Radialis Brevis and Extensor Pollicis Longus Reroutement. AB - The flexor carpi ulnaris to extensor carpi radialis brevis transfer and extensor pollicis longus rerouting combined with thenar release are 2 successful surgical interventions for children with spastic cerebral palsy. The goal of both procedures is to improve quality of life for patients who have previously failed conservative management, and the degree of expected improvement is predicated on several patient variables, making careful patient selection crucial for ensuring successful outcomes. Here, surgical technique is described; risk factors are discussed, and outcomes related to both procedures are presented. PMID- 27387087 TI - An Update on Upper Extremity Tendon Transfers. PMID- 27387088 TI - Tree demography dominates long-term growth trends inferred from tree rings. AB - Understanding responses of forests to increasing CO2 and temperature is an important challenge, but no easy task. Tree rings are increasingly used to study such responses. In a recent study, van der Sleen et al. (2014) Nature Geoscience, 8, 4 used tree rings from 12 tropical tree species and find that despite increases in intrinsic water use efficiency, no growth stimulation is observed. This challenges the idea that increasing CO2 would stimulate growth. Unfortunately, tree ring analysis can be plagued by biases, resulting in spurious growth trends. While their study evaluated several biases, it does not account for all. In particular, one bias may have seriously affected their results. Several of the species have recruitment patterns, which are not uniform, but clustered around one specific year. This results in spurious negative growth trends if growth rates are calculated in fixed size classes, as 'fast-growing' trees reach the sampling diameter earlier compared to slow growers and thus fast growth rates tend to have earlier calendar dates. We assessed the effect of this 'nonuniform age bias' on observed growth trends and find that van der Sleen's conclusions of a lack of growth stimulation do not hold. Growth trends are - at least partially - driven by underlying recruitment or age distributions. Species with more clustered age distributions show more negative growth trends, and simulations to estimate the effect of species' age distributions show growth trends close to those observed. Re-evaluation of the growth data and correction for the bias result in significant positive growth trends of 1-2% per decade for the full period, and 3-7% since 1950. These observations, however, should be taken cautiously as multiple biases affect these trend estimates. In all, our results highlight that tree ring studies of long-term growth trends can be strongly influenced by biases if demographic processes are not carefully accounted for. PMID- 27387089 TI - Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid. AB - OBJECTIVE: The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. METHODS: The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4) Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). RESULTS: In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. CONCLUSION: It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content. PMID- 27387090 TI - End-to-End Optimization of High-Throughput DNA Sequencing. AB - At the core of Illumina's high-throughput DNA sequencing platforms lies a biophysical surface process that results in a random geometry of clusters of homogeneous short DNA fragments typically hundreds of base pairs long-bridge amplification. The statistical properties of this random process and the lengths of the fragments are critical as they affect the information that can be subsequently extracted, that is, density of successfully inferred DNA fragment reads. The ensembles of overlapping DNA fragment reads are then used to computationally reconstruct the much longer target genome sequence. The success of the reconstruction in turn depends on having a sufficiently large ensemble of DNA fragments that are sufficiently long. In this article using stochastic geometry, we model and optimize the end-to-end flow cell synthesis and target genome sequencing process, linking and partially controlling the statistics of the physical processes to the success of the final computational step. Based on a rough calibration of our model, we provide, for the first time, a mathematical framework capturing the salient features of the sequencing platform that serves as a basis for optimizing cost, performance, and/or sensitivity analysis to various parameters. PMID- 27387091 TI - Comparison of GeneFinder human papillomavirus (HPV) Liquid Beads Microarray PCR Kit and Hybrid Capture 2 Assay for Detection of HPV Infection. AB - BACKGROUND: Along with advances in methodological technologies, various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced. The GeneFinder HPV liquid beads microarray PCR kit is one of the recently developed. Our aim was to compare the performance of GeneFinder to Hybrid Capture 2 for detection of HR HPV. METHODS: A total of 900 cervical swab specimens were obtained. All specimens were submitted for HR HPV detection with Hybrid Capture 2 (HC2) and GeneFinder and then additionally analyzed the discordant or both positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. RESULTS: Hybrid Capture 2 detected 12.8% cases and GeneFinder detected 15.8% cases with 13 HR HPV types. Also, GeneFinder detected 27.4% cases for 32 detectable HPV types. The overall agreement rate was 93.2% with 0.724 kappa coefficient. Discordant results between these two assays were observed in 56 cases. HC2 showed sensitivity of 83.5% and specificity of 95.9%, while GeneFinder showed sensitivity of 85.4% and specificity of 91.9%. For HPV 16 or HPV 18 detection, GeneFinder showed 95.0% or 66.7% of sensitivity and 99.2% or 100%, respectively. Overall coinfection rate was 15.4% (38/247) in GeneFinder analysis. CONCLUSIONS: Considering the high agreement rate with HC2, high sensitivity and the ability to differentiate 32 HPV genotypes including HPV 16/18, GeneFinder could be used as a laboratory testing method for the screening of HPV infections. The use of GeneFinder may also contribute to future research associated with the significance of various HPV types and multiple coinfections. PMID- 27387092 TI - A heterojunction photocatalyst composed of zinc rhodium oxide, single crystal derived bismuth vanadium oxide, and silver for overall pure-water splitting under visible light up to 740 nm. AB - We recently reported the synthesis of a solid-state heterojunction photocatalyst consisting of zinc rhodium oxide (ZnRh2O4) and bismuth vanadium oxide (Bi4V2O11), which functioned as hydrogen (H2) and oxygen (O2) evolution photocatalysts, respectively, connected with silver (Ag). Polycrystalline Bi4V2O11 (p-Bi4V2O11) powders were utilized to form ZnRh2O4/Ag/p-Bi4V2O11, which was able to photocatalyze overall pure-water splitting under red-light irradiation with a wavelength of 700 nm (R. Kobayashi et al., J. Mater. Chem. A, 2016, 4, 3061). In the present study, we replaced p-Bi4V2O11 with a powder obtained by pulverizing single crystals of Bi4V2O11 (s-Bi4V2O11) to form ZnRh2O4/Ag/s-Bi4V2O11, and demonstrated that this heterojunction photocatalyst had enhanced water-splitting activity. In addition, ZnRh2O4/Ag/s-Bi4V2O11 was able to utilize nearly the entire range of visible light up to a wavelength of 740 nm. These properties were attributable to the higher O2 evolution activity of s-Bi4V2O11. PMID- 27387093 TI - Deterministic sequential isolation of floating cancer cells under continuous flow. AB - Isolation of rare cells, such as circulating tumor cells, has been challenging because of their low abundance and limited timeframes of expressions of relevant cell characteristics. In this work, we devise a novel hydrodynamic mechanism to sequentially trap and isolate floating cells in biosamples. We develop a microfluidic device for the sequential isolation of floating cancer cells through a series of microsieves to obtain up to 100% trapping yield and >95% sequential isolation efficiency. We optimize the trappers' dimensions and locations through both computational and experimental analyses using microbeads and cells. Furthermore, we investigated the functional range of flow rates for effective sequential cell isolation by taking the cell deformability into account. We verify the cell isolation ability using the human breast cancer cell line MDA-MB 231 with perfect agreement with the microbead results. The viability of the isolated cells can be maintained for direct identification of any cell characteristics within the device. We further demonstrate that this device can be applied to isolate the largest particles from a sample containing multiple sizes of particles, revealing its possible applicability in isolation of circulating tumor cells in cancer patients' blood. Our study provides a promising sequential cell isolation strategy with high potential for rapid detection and analysis of general floating cells, including circulating tumor cells and other rare cell types. PMID- 27387094 TI - Oxidative stress in otosclerosis. AB - OBJECTIVES: Otosclerosis is a disease involving abnormal bone turnover in the human otic capsule that results in hearing loss. Several hypotheses have been suggested for the etiopathogenesis of otosclerosis; however, its etiology remains unclear. METHODS: This study evaluated the correlation between otosclerosis and levels of paraoxonase-1 (PON1), arylesterase, total antioxidant status, total oxidant status (TOS), oxidative stress index (OSI), total sulfhydryl (-SH) groups, lipid hydroperoxide, and ceruloplasmin in the serum of otosclerosis patients and healthy subjects with respect to oxidative stress. RESULTS: In our study, TOS and OSI levels were higher in the otosclerosis patients than in the controls. The PON1 levels showed that oxidative stress was severe, and as a result, antioxidants were consumed and depleted. DISCUSSION: When an imbalance between oxygen free radical production and antioxidative defense mechanisms occurs, reactive oxygen species levels may increase, which in turn may damage cells and tissues through the peroxidation of phospholipid membrane structures. The body initially responds with increased antioxidant production, but if the oxidative stress is severe, decreased antioxidant levels may result. This study reports expression levels of oxidative stress species in otosclerosis patients. PMID- 27387095 TI - Enantioselective synthesis of 2,3-disubstituted trans-2,3-dihydrobenzofurans using a Bronsted base/thiourea bifunctional catalyst. AB - The diastereo- and enantioselective synthesis of 2,3-disubstituted trans-2,3 dihydrobenzofuran derivatives (15 examples, up to 96 : 4 dr, 95 : 5 er) via intramolecular Michael addition has been developed using keto-enone substrates and a bifunctional tertiary amine-thiourea catalyst. This methodology was extended to include non-activated ketone pro-nucleophiles for the synthesis of 2,3-disubstituted indane and 3,4-disubstituted tetrahydrofuran derivatives. PMID- 27387096 TI - Patient-centered support in the survivorship care transition: Outcomes from the Patient-Owned Survivorship Care Plan Intervention. AB - BACKGROUND: To the authors' knowledge, few studies to date have evaluated the effects of survivorship care planning on the care transition process from specialty cancer care to self-management and primary care, patient experience, or health outcomes. The Patient-owned Survivorship Transition Care for Activated, Empowered survivors (POSTCARE) is a single coaching encounter based on the Chronic Care Model that uses motivational interviewing techniques to engage survivors of breast cancer. The current study examined the effects of the POSTCARE intervention on patient outcomes and care coordination. METHODS: A total of 79 survivors of American Joint Commision on Cancer TNM System stage 0 to IIIB breast cancer were randomized to POSTCARE (40 patients) or usual care (39 patients). Patient outcomes were assessed using the 36-Item Short Form Health Survey (SF-36), Social/Role Activities Limitations, Self-Efficacy for Managing Chronic Disease 6-Item Scale, the Patient Activation Measure-Short Form, and Patient Health Questionnaire depression scale at baseline and at 3-month follow up. Care coordination was assessed using confirmed primary care physician visits and reported discussion of the survivorship care plan at the 3-month follow-up. Logistic and linear regression analyses were conducted to examine the effect of POSTCARE on selected outcomes. RESULTS: Participants in the intervention group versus those receiving usual care demonstrated significantly higher self-reported health (F-statistic (3,71), 3.63; P =.017) and lower social role limitations (F (3,70), 3.82; P =.014) and a trend toward greater self-efficacy (F (3,69), 2.51; P = .07). Three quality-of-life domains reached clinically meaningful improvement at the 3-month follow-up, including physical role (P =.0009), bodily pain (P =.03), and emotional role (P =.04). CONCLUSIONS: The POSTCARE intervention appeared to have a positive impact on patient outcomes and demonstrated promise as a strategy with which to improve survivors' experience, care coordination, and health outcomes. Cancer 2016;122:3232-42. (c) 2016 American Cancer Society. PMID- 27387097 TI - Modeling in Real Time During the Ebola Response. AB - To aid decision-making during CDC's response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC activated a Modeling Task Force to generate estimates on various topics related to the response in West Africa and the risk for importation of cases into the United States. Analysis of eight Ebola response modeling projects conducted during August 2014-July 2015 provided insight into the types of questions addressed by modeling, the impact of the estimates generated, and the difficulties encountered during the modeling. This time frame was selected to cover the three phases of the West African epidemic curve. Questions posed to the Modeling Task Force changed as the epidemic progressed. Initially, the task force was asked to estimate the number of cases that might occur if no interventions were implemented compared with cases that might occur if interventions were implemented; however, at the peak of the epidemic, the focus shifted to estimating resource needs for Ebola treatment units. Then, as the epidemic decelerated, requests for modeling changed to generating estimates of the potential number of sexually transmitted Ebola cases. Modeling to provide information for decision-making during the CDC Ebola response involved limited data, a short turnaround time, and difficulty communicating the modeling process, including assumptions and interpretation of results. Despite these challenges, modeling yielded estimates and projections that public health officials used to make key decisions regarding response strategy and resources required. The impact of modeling during the Ebola response demonstrates the usefulness of modeling in future responses, particularly in the early stages and when data are scarce. Future modeling can be enhanced by planning ahead for data needs and data sharing, and by open communication among modelers, scientists, and others to ensure that modeling and its limitations are more clearly understood. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27387099 TI - Experimental models of sarcoidosis. AB - PURPOSE OF REVIEW: Sarcoidosis is a disease caused by a complex combination of genetic susceptibility, immune networks and infectious and/or environmental agents. The onset and phenotypic variability of sarcoidosis remain poorly elucidated, not only due to the lack of clearly identified causes, but also because it is widely considered that no reliable model of this disease is available. In this review, we discuss the various models of granulomatous diseases in order to challenge this assertion. RECENT FINDINGS: A large number of models of granulomatous diseases are available, both cellular models used to study the natural history of granulomas and experimental animal models mostly developed in rodents. SUMMARY: Although none of the available models fully reproduces sarcoidosis, most of them generate various data supporting key concepts. Selected models with a high level of confidence among those already published may provide various pieces of the sarcoidosis jigsaw puzzle, whereas clinical data can provide other elements. A 'systems biology' approach for modelling may be a way of piecing together the various pieces of the puzzle. Finally, experimental models and a systemic approach should be considered to be tools for preclinical evaluation of the efficacy of drugs prior to testing in clinical trials. PMID- 27387098 TI - Clinical profile and in-hospital outcome of Caucasian patients with takotsubo syndrome and right ventricular involvement. AB - AIM: To determine the prevalence, clinical characteristics, in-hospital course and determinants of major adverse events in a cohort of Caucasian patients with Takotsubo syndrome (TTS) and right ventricular involvement (RVi), regardless of left ventricular variant forms. METHODS AND RESULTS: The study population consisted of 424 patients (mean age 69.1+/-11.5years; female 92.2%) with a diagnosis of TTS divided into two groups according to the presence or absence of RVi. RVi patients (n=57; 13.4%) showed a higher prevalence of comorbidities, especially respiratory diseases (p=0.011), and a higher Charlson comorbidity index (CCI; p=0.006) than non-RVi patients. In-hospital major adverse events (acute heart failure, cardiogenic shock and death) occurred more frequently in RVi patients (p<0.001). Heart rate and CCI, along with the echocardiographic parameters of wall motion score index, E/e' ratio, tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) were associated with adverse in-hospital outcome. At multivariate analysis, CCI (HR: 1.871; 95% CI: 1.202-2.912; p=0.006), sPAP (HR: 1.059; 95% CI: 1.016-1.104; p=0.007) and TAPSE (HR: 0.728; 95% CI: 0.619-0.855; p<0.001) were independent correlates of the composite outcome in patients with RVi. CONCLUSION: Patients with RVi are characterized by distinct clinical profile and should undergo closely clinical and echocardiographic monitoring. The presence of echocardiographic signs of right ventricular failure along with substantial comorbidities burden identify a cohort at higher risk of in-hospital major adverse cardiovascular events. PMID- 27387100 TI - Innate immunity in sarcoidosis pathobiology. AB - PURPOSE OF REVIEW: The immunopathogenesis of sarcoidosis is considered to involve contributions from both adaptive and innate immune responses. Although the identification of adaptive responses to candidate pathogenic antigens will elucidate mechanisms that regulate inflammation in sarcoidosis, innate mechanisms likely represent the 'missing link' to the initiation, maintenance, and resolution of noncaseating granulomatous inflammation, the hallmark feature of sarcoidosis. Furthermore, environments that expose patients to candidate pathogenic antigens for sarcoidosis also provide opportunities for engagement with innate ligands. RECENT FINDINGS: Several studies have identified enhanced responsiveness via pattern recognition receptor pathways, potentiating the local induction of cytokines relevant to granulomatous inflammation, such as through stimulation of nucleotide-binding oligomerization domain-like receptor and Toll like receptor pathways. These pathways contribute to the inherent properties of granulomas including, in some cases, persistent localization of pathogens and antigen. Serum amyloid A has been identified to be abundant in sarcoidosis tissues, and this promiscuous host protein can serve as an innate ligand to regulate experimental granulomatous inflammation. Nascent evidence supports a potential role for alternatively activated macrophages to direct histopathological outcomes in sarcoidosis. SUMMARY: Innate pathways deserve further investigation as potential therapeutic targets for inhibiting granuloma formation in sarcoidosis. PMID- 27387101 TI - Interferon-induced pulmonary hypertension: an update. AB - PURPOSE OF REVIEW: Pulmonary adverse effects of interferon (IFN) therapies are rare but can be life threatening. This article proposes to review clinical and experimental data suggesting a causal link between interferon exposure and pulmonary arterial hypertension (PAH). RECENT FINDINGS: Interferon has recently been added to the list of possible risk factors for PAH. This was justified by the reporting of many cases of pulmonary hypertension potentially associated with IFN-alpha or IFN-beta exposure. Some of them were reversible after cessation of interferon exposure, especially in patients without concomitant risk factors for pulmonary hypertension. In contrast, it remains a challenge to definitively confirm the causal role of IFN-alpha in patients treated for hepatitis C viral infection because of frequent concomitant PAH risk factors such as portal hypertension and/or HIV infection. In these patients, temporal and clinical arguments suggest that interferon may potentially act as an additional trigger for PAH. Moreover, the information obtained from clinical experience with interferon therapy has been enriched by basic science research on this topic suggesting that interferon is involved in both human and experimental pulmonary hypertension. SUMMARY: Many clinical and experimental data corroborate the link between interferon exposure and the risk to develop PAH. PMID- 27387102 TI - Pulmonary tumour thrombotic microangiopathy. AB - PURPOSE OF REVIEW: Pulmonary tumour thrombotic microangiopathy (PTTM) describes tumour cell microemboli with occlusive fibrointimal remodelling in small pulmonary arteries, veins and lymphatics. Progressive vessel occlusion ultimately results in pulmonary hypertension, which is often severe and rapid in onset. PTTM is associated with carcinomas, notably gastric carcinoma, with vascular endothelial growth factor and platelet-derived growth factor (PDGF) signalling implicated in driving the intimal remodelling. PTTM is a rare cause of pulmonary hypertension, but given that up to a quarter of autopsy specimens from patients dying of carcinoma show evidence for PTTM, it is probably underdiagnosed. RECENT FINDINGS: Until recently, prognosis in PTTM was universally abysmal from weeks to a few months. Diagnostic utilities include aspiration of tumour cells at wedged right heart catheterization, high-resolution computed tomography (HRCT) findings and computed tomography-positron emission tomography (CT-PET), although definitive diagnosis requires histological analysis. Reports of PTTM treated with a combination of targeted pulmonary vasodilator therapies, anticoagulation, specific chemotherapy and PDGF inhibition, for example using imatinib, suggest that these approaches can prolong survival. SUMMARY: PTTM is increasingly recognized as an important cause of pulmonary hypertension, often in patients presenting with new-onset pulmonary hypertension and as yet undiagnosed malignancy. Prospects of survival are improving with targeted combination therapy, and early recognition and diagnosis are likely to be the key factors to improve outcome. PMID- 27387103 TI - Long Term Outcome of Routine Image-enhanced Endoscopy in Newly Diagnosed Head and Neck Cancer: a Prospective Study of 145 Patients. AB - Synchronous second primary tumors (SPTs), especially esophageal squamous cell neoplasia (ESCN), in patients with head and neck squamous cell carcinoma (HNSCC) are not uncommon. Image-enhanced endoscopy (IEE) screening may identify SPTs while there is no evidence to support its benefit. We prospectively recruited an adult cohort with newly-diagnosed HNSCC for IEE screening of upper gastrointestinal (UGI) tract neoplasia. 145 HNSCC patients were recruited. 22 (15.2%) patients had synchronous UGI tract neoplasia, including 20 ESCNs and 2 gastric adenocarcinoma. At a median follow-up of 2.72 (+/-1.73) years, the 3-year overall survival (OS) rate was 0.71. HNSCC patients with synchronous ESCN/UGI tract neoplasia had poorer prognosis than those without (multivariate analysis, hazard ratio [HR] 2.75/2.79, 95% confidence interval [CI] 1.11~6.82/1.15~6.80, p = 0.03/0.02). HNSCC patients with advanced (stage III&IV) ESCN had worst survivals (p < 0.001). Among those with synchronous ESCNs, hypopharyngeal cancers were associated with poorer prognosis when compared with oral cancers (HR 2.36, 95% CI 1.08~5.15, p = 0.03). IEE screening for UGI SPTs in HNSCC patients could be used for risk stratification and prognosis prediction. HNSCC patients with advanced ESCN had the worst prognosis. Further studies are needed to demonstrate the survival benefits from IEE screening. PMID- 27387104 TI - Neuromas as the cause of pain in the residual limbs of amputees. An ultrasound study. AB - AIM: To explore the morphology of neuromas and to determine the differences, if any, between asymptomatic and symptomatic neuromas using ultrasound. MATERIALS AND METHODS: Eighty patients with symptomatic neuromas were included in this retrospective review. High-resolution ultrasound examination was performed. Transducer pressure allowed real-time analysis of both symptomatic and asymptomatic neuromas. Quantifiable assessment of pain by the patient assigned a pain score of 0, 1, 2, or 3, to each neuroma. RESULTS: One hundred and fifty-nine neuromas were identified in total. Fifty-three neuromas were asymptomatic (pain score=0), very severe pain was recorded in 54 (pain score=3), 16 neuromas were mildly painful (pain score=1) and 36 were moderately painful (pain score=2). The average number of neuromas per patient was 1.98, and the average number of symptomatic neuromas per patient was 1.3. There was no correlation between pain score and patient age, neuroma volume, amputation type, and time since amputation. CONCLUSIONS: High-resolution ultrasound can distinguish between asymptomatic and symptomatic neuromas. Patient age, time since amputation, the type of amputation, and the neuroma volume were not related to the presence of pain. PMID- 27387105 TI - The role of 18F-FDG PET/CT in the management of patients with secondary haemophagocytic lymphohistiocytosis. AB - AIM: To investigate the ability of combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F FDG) positron-emission tomography (PET)/computed tomography (CT) to determine potential causes of secondary haemophagocytic lymphohistiocytosis (sHLH) and to predict prognosis. MATERIAL AND METHODS: Forty-three patients (male/female 20/23, median age 48.5 years), who were diagnosed with sHLH and underwent FDG-PET/CT before treatment, were retrospectively reviewed. The clinical characteristics were compared to identify the predictors of high-yield FDG-PET/CT. Univariate and multivariate analyses were conducted to identify factors associated with survival. Statistical analysis was performed using SPSS version 19.0. RESULTS: PET results were helpful in 65.1% (28/43), whilst non-contributory in 34.9% (15/43) of patients with regard to the final diagnosis. Lymphoma was the most common (25/43) reason for sHLH, and patients with focal FDG uptake were more likely to be diagnosed with underlying diseases. C-reactive protein (CRP) was found to be a good indicator for the usefulness of PET/CT in HLH patients. Multivariate analysis showed that therapy regimen (hazard ratio [HR]=4.99, p=0.026), fibrinogen (FBG) <1.5 g/l (HR=3.87, p=0.049) and spleen:mediastinum ratio (SP/M) (HR=7.44, p=0.006) were independent prognostic factors for survival. CONCLUSION: FDG-PET/CT could be a useful technique for detecting underlying diseases causing sHLH. CRP was a useful predictor of FDG-PET/CT effectiveness. Therapy regimen, FBG level, and SP/M were independent prognostic factors for HLH survival. PMID- 27387120 TI - Communication about sexual health with breast cancer survivors: Variation among patient and provider perspectives. AB - OBJECTIVE: Breast cancer survivors experience a range of sexual health (SH) issues. Communication problems between patient and provider can prevent survivors from pursuing SH goals and can negatively influence biopsychosocial outcomes. The primary aims of this study were to identify provider communication behaviors that facilitate or impede clinical interactions regarding SH (according to survivors and providers) and to highlight discrepancies that affect care. METHODS: Forty breast cancer survivors and forty health care providers from a variety of specialties participated in semi-structured interviews informed by the Critical Incident Technique. Transcripts were thematically analyzed using the constant comparative method. RESULTS: Survivors and providers discussed the importance of honoring individual patient needs and conveying compassionate messages. However, accounts varied significantly regarding the appropriate timing and method of initiating SH discussions and the helpfulness of certain support behaviors and linguistic devices. CONCLUSION: Provider and survivor accounts of what constitutes helpful and unhelpful provider communication behaviors when discussing SH concerns are misaligned in nuanced and meaningful ways. These discrepancies reveal potential areas for educational intervention. PRACTICE IMPLICATIONS: SH discussions require providers to examine assumptions about patients' communication preferences and information needs. Patients may benefit from frank yet sensitive discussions earlier in the cancer continuum. PMID- 27387121 TI - Can stories influence African-American patients' intentions to change hypertension management behaviors? A randomized control trial. AB - OBJECTIVES: Information-only interventions for hypertension management have limited effectiveness, particularly among disadvantaged populations. We assessed the impact of viewing African-American patients' stories of successfully controlling hypertension on intention to change hypertension management behaviors and engagement with educational materials. METHODS: In a three-site randomized trial, 618 African-American Veterans with uncontrolled hypertension viewed an information-only DVD about hypertension (control) or a DVD adding videos of African-American Veterans telling stories about successful hypertension management (intervention). After viewing, patients were asked about their engagement with the DVD, and their intentions to change behavior. Mean scores were compared with two-sided t-tests. RESULTS: Results favored the Stories intervention, with significantly higher emotional engagement versus control (4.3 vs. 2.2 p<0.0001). Intervention patients reported significantly greater intentions to become more physically active (4.6 vs. 4.4, p=0.018), use salt substitutes (3.9 vs. 3.4, p=0.006), talk openly with their doctor about hypertension (4.6 vs. 4.5, p=0.049), and remember to take hypertension medication (4.8 vs. 4.6, p=0.04). CONCLUSION: Patients were more emotionally engaged and reported intentions to change behavior when watching real patient hypertension management success stories. PRACTICE IMPLICATIONS: Stories may be more influential than information alone, and represent a scalable approach to modifying behavioral intention. PMID- 27387122 TI - Patients' knowledge about symptoms and adequate behaviour during acute myocardial infarction and its impact on delay time: Findings from the multicentre MEDEA Study. AB - OBJECTIVE: We aimed to assess whether patients' knowledge about acute myocardial infarction (AMI) has an impact on the prehospital delay-time. METHODS: This investigation was based on 486 AMI patients who participated in the cross sectional Munich-Examination-of-Delay-in-Patients-Experiencing-Acute-Myocardial Infarction (MEDEA) study. A modified German-version of the ACS-Response-Index Questionnaire was used. Multivariate logistic-regression models were used to identify factors associated with knowledge-level as well as the impact of knowledge-level on delay-time. RESULTS: High AMI-knowledge shortened median delay time in men (168[92-509] vs. 276[117-1519] mins, p=0.0069), and in women (189[101 601] vs. 262[107-951]mins, p=0.34). Almost half-of-patients (n=284,58%) demonstrated high AMI-knowledge. High-knowledge were independently associated with male-gender (OR=1.47[1.17-1.85]) and General-Practitioner as a knowledge source (OR=1.42[1.14-1.77]). Old-age (OR=0.87[0.86-0.89]) and previous AMI history/stent-placement (OR=0.65[0.46-0.93]) were significantly associated with lower-knowledge. Although the majority (476,98%) correctly recognized at least one AMI-symptom, 69(14.2%) patients correctly identified all AMI-symptoms. Additionally, one-in-three believed that heart-attack is always accompanied with severe chest-pain. Elderly-patients and women were more likely to be less knowledgeable about atypical-symptoms (p=0.006), present with atypical AMI presentation (p<0.001) and subsequently experience protracted delay-times (p<0.001). CONCLUSIONS: Knowledge of AMI-symptoms remains to be substandard, especially knowledge of atypical-symptoms. Knowledge is essential to reduce delay times, but it is not a panacea, since it is not sufficient alone to optimize prehospital delay-times. PMID- 27387123 TI - Re: Predicting Prostate Cancer-specific Outcome After Radical Prostatectomy Among Men with Very High-risk cT3b/4 PCa: A Multi-institutional Outcome Study of 266 Patients. PMID- 27387124 TI - Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self renewal of Human Bladder Cancer Stem Cells. AB - : Cancer stem cells are considered responsible for many important aspects of tumors such as their self-renewal, tumor-initiating, drug-resistance and metastasis. However, the genetic basis and origination of human bladder cancer stem cells (BCSCs) remains unknown. Here, we conducted single-cell sequencing on 59 cells including BCSCs, bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. Moreover, 21 key altered genes were identified in BCSCs including six genes not previously described in BC (ETS1, GPRC5A, MKL1, PAWR, PITX2 and RGS9BP). Co-mutations of ARID1A, GPRC5A and MLL2 introduced by CRISPR/Cas9 significantly enhance the capabilities of self-renewal and tumor-initiating of BCNSCs. To our knowledge, our study first provides an overview of the genetic basis of human BCSCs with single-cell sequencing and demonstrates the biclonal origin of human BCSCs via evolution analysis. PATIENT SUMMARY: Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self renewal. PMID- 27387125 TI - Re: Intermittent Androgen Deprivation (IAD) in Prostate Cancer (PC): Are We Ready To Quit? PMID- 27387126 TI - Surface enhanced Raman scattering of melamine on silver substrate: An experimental and DFT study. AB - Surface enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy technique that allows amplifying weak Raman signals by the excitation of localized surface plasmons. In this paper, we used nanoscale roughened silver surface to enhance Raman signals of melamine analyte. Silver nanoparticles were synthesized by wet-chemical method and employed for SERS measurement. Theoretically, optimized geometries and vibrational frequencies of melamine and melamine absorbed on silver-cluster surface were calculated by using the B3LYP/6 31G(d) method. Then, the predicted spectrograms are compared with the experimental Raman spectra. As a result, Raman signals of melamine were dramatically enhanced by using obtained silver nanoparticles as the substrate. Typical peaks of melamine at 676 and 983cm(-1) were enhanced and could be obviously observed in experiments. The calculated vibrational frequencies seem to relatively coincide with the experimental values. SERS effect of melamine on nanoscale silver was also explained by analyzing molecular frontier orbitals (HOMO and LUMO) melamine-silver complexes. PMID- 27387127 TI - Adsorbed molecules in external fields: Effect of confining potential. AB - We study the rotational excitation of a molecule adsorbed on a surface. As is well known the interaction potential between the surface and the molecule can be modeled in number of ways, depending on the molecular structure and the geometry under which the molecule is being adsorbed by the surface. We explore the effect of change of confining potential on the excitation, which is largely controlled by the static electric fields and continuous wave laser fields. We focus on dipolar molecules and hence we restrict ourselves to the first order interaction in field-molecule interaction potential either through permanent dipole moment or/and the molecular polarizability parameter. It is shown that confining potential shapes, strength of the confinement, strongly affect the excitation. We compare our results for different confining potentials. PMID- 27387128 TI - Activation of the miR-34a/SIRT1/p53 Signaling Pathway Contributes to the Progress of Liver Fibrosis via Inducing Apoptosis in Hepatocytes but Not in HSCs. AB - Liver fibrosis results from a sustained wound healing response to chronic liver injury, and the activation of nonparenchymal hepatic stellate cells (HSCs) is the pivotal process. MicroRNA-34a (miR-34a) is the direct target gene of p53 and activates p53 through sirtuin 1 (SIRT1) simultaneously. The miR-34a/SIRT1/p53 signaling pathway thus forms a positive feedback loop wherein p53 induces miR-34a and miR-34a activates p53 by inhibiting SIRT1, playing an important role in cell proliferation and apoptosis. miR-34a expression has been found to be increased in animal models or in human patients with different liver diseases, including liver fibrosis. However, the exact role of this classical miR-34a/SIRT1/p53 signaling pathway in liver fibrosis remains unclear. In the present study, using a CCl4 induced rat liver fibrosis model, we found that the miR-34a/SIRT1/p53 signaling pathway was activated and could be inhibited by SIRT1 activator SRT1720. Further studies showed that the miR-34a/SIRT1/p53 signaling pathway was activated in hepatocytes but not in HSCs. The activation of this pathway in hepatocytes resulted in the apoptosis of hepatocytes and thus activated HSCs. Our data indicate that the miR-34a/SIRT1/p53 signaling pathway might be a promising therapeutic target for liver fibrosis. PMID- 27387129 TI - Association of nevus count with prevention attitudes and behaviors before melanoma diagnosis. AB - Although melanoma risk factors are commonly known to healthcare professionals, the extent to which the at-risk public is either aware of these factors or perceives their risk accordingly has rarely been studied. We sought to investigate whether the presence of known melanoma risk factors, such as high total nevus and atypical nevus counts, was associated with increased prevention attitudes and behaviors, such as skin self-examinations and physician skin examinations. This was a retrospective study of 566 individuals recently diagnosed with melanoma in two large academic centers. Most prevention attitudes and behaviors did not vary on the basis of total nevi or atypical nevi counts. However, younger patients (<60 years) with many total nevi (>50) were more likely than those with fewer nevi (<20) to believe that they were at-risk for melanoma (42 vs. 23%; P<0.05), and more likely to state that they had been instructed on the signs of melanoma (36 vs. 21%; P<0.05). Patient and health provider recognition of the impact of nevus count on melanoma risk presents a unique and mostly untapped opportunity for earlier detection. PMID- 27387130 TI - Zinc-modified titanium surface enhances osteoblast differentiation of dental pulp stem cells in vitro. AB - Zinc is an essential trace element that plays an important role in differentiation of osteoblasts and bone modeling. This in vitro study aimed to evaluate the osteoblast differentiation of human dental pulp stem cells (DPSCs) on zinc-modified titanium (Zn-Ti) that releases zinc ions from its surface. Based on real-time PCR, alkaline phosphatase (ALP) activity and Western blot analysis data, we investigated osteoblast differentiation of DPSCs cultured on Zn-Ti and controls. DPSCs cultured on Zn-Ti exhibited significantly up-regulated gene expression levels of osteoblast-related genes of type I collagen (Col I), bone morphogenetic protein 2 (BMP2), ALP, runt-related transcription factor 2 (Runx2), osteopontin (OPN), and vascular endothelial growth factor A (VEGF A), as compared with controls. We also investigated extracellular matrix (ECM) mineralization by Alizarin Red S (ARS) staining and found that Zn-Ti significantly promoted ECM mineralization when compared with controls. These findings suggest that the combination of Zn-Ti and DPSCs provides a novel approach for bone regeneration therapy. PMID- 27387132 TI - The coupling of hemin with persistent free radicals induces a nonradical mechanism for oxidation of pollutants. AB - Herein, we report that persistent free radicals (PFRs) based on MWCNTs significantly accelerate the pollutant removal rate. EPR measurement combined with the electrochemical test indicated that a nonradical mechanism was responsible for the enhancement, which is different from the previously reported radical pathway on PFRs. PMID- 27387131 TI - A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia. AB - Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI-WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression-free survival (PFS) of ofatumumab as front-line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89% (1996 NCI-WG criteria), respectively (54 and 68%, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24-month estimated PFS rates were 46 and 78%, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high-risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well-tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020-1025, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27387133 TI - Cathepsin S attenuates endosomal EGFR signalling: A mechanical rationale for the combination of cathepsin S and EGFR tyrosine kinase inhibitors. AB - EGF-mediated EGFR endocytosis plays a crucial role in the attenuation of EGFR activation by sorting from early endosomes to late endosomes and transporting them into lysosomes for the final proteolytic degradation. We previously observed that cathepsin S (CTSS) inhibition induces tumour cell autophagy through the EGFR mediated signalling pathway. In this study, we further clarified the relationship between CTSS activities and EGFR signalling regulation. Our results revealed that CTSS can regulate EGFR signalling by facilitating EGF-mediated EGFR degradation. CTSS inhibition delayed the EGFR degradation process and caused EGFR accumulation in the late endosomes at the perinuclear region, which provides spatial compartments for prolonged EGFR and sustained downstream signal transducer and activator of transcription 3 and AKT signalling. Notably, cellular apoptosis was markedly enhanced by combining treatment with the EGFR inhibitor Iressa and CTSS inhibitor 6r. The data not only reveal a biological role of CTSS in EGFR signalling regulation but also evidence a rationale for its clinical evaluation in the combination of CTSS and EGFR tyrosine kinase inhibitors. PMID- 27387134 TI - Too Many Is Too Bad: Long-Term Net Negative Effects of High Density Ungulate Populations on a Dominant Mediterranean Shrub. AB - Plant-animal interactions imply costs and benefits with net balance depending on interacting species and ecological context. Ungulates, in particular, confer costs (e.g., plant leaf consumption, flower bud predation) and benefits (e.g., plant overcompensation, seed dispersal) to plants. Magnitude of costs and benefits may be altered by habitat management or ecological conditions favoring high density ungulate populations. Little is known however on whether plant costs or benefits predominate over the years, or the long-term outcomes of plant-animal interactions in habitat types sustaining high density ungulate populations. We investigated how high density ungulate populations alter plant costs and benefits by quantifying ungulate long-term effects on the shrub Cistus ladanifer (Cistaceae) individual size, seed weight and number, seed bank, and population density, through a 12-year ungulate exclusion experiment in a Mediterranean scrubland. We monitored plant size and flower buds in plants exposed or protected from ungulates and number of developed capsules and seeds consumed (potential seed dispersal) by ungulates during three reproductive seasons. We found that ungulates negatively affected shrub size and led to a dramatically decline of shrub reproductive structures and seed production, affecting the plant reproductive cycle. Number of buds was 27 times higher and number of developed seed 5 times higher in ungulate-excluded as compared to ungulate-exposed plots. After 9 years of ungulate exclusion, the C. ladanifer seed bank was 2.6 times higher in ungulate-excluded plots. The population density of C. ladanifer was 4 times higher in ungulate-excluded plots. Our long-term experiment showed that high density ungulate populations can alter plant-animal interactions by reducing plant benefits and increasing plant costs. PMID- 27387135 TI - Assessment of the Accuracy of Using ICD-9 Codes to Identify Uveitis, Herpes Zoster Ophthalmicus, Scleritis, and Episcleritis. AB - IMPORTANCE: With the increased use of data from electronic medical records for research, it is important to validate International Classification of Diseases, Ninth Revision (ICD-9) codes for their respective diagnoses. OBJECTIVE: To assess the accuracy of using ICD-9 codes to identify ocular inflammatory diseases. DESIGN, SETTING, AND PARTICIPANTS: Retrospective secondary database analysis. The setting was Kaiser Permanente Hawaii, an integrated managed care consortium that serves approximately 15% of the general Hawaiian population. Participants were patients with ICD-9 diagnosis codes that might be associated with a diagnosis of ocular inflammation seen at Kaiser Permanente Hawaii between January 1, 2006, and December 31, 2007. The data collection and analysis took place from January 2011 to August 2015. MAIN OUTCOMES AND MEASURES: The main outcome was the positive predictive value (PPV) of ICD-9 codes for identifying specific types of ocular inflammatory disease. The PPVs were calculated by determining the ratio of the confirmed cases found by medical record review to the total number of cases identified by ICD-9 code. RESULTS: Of the 873 patients identified by a comprehensive list of ICD-9 codes for ocular inflammatory diseases, 224 cases were confirmed as uveitis after medical record review. Using a set of uveitis specific codes and eliminating patients with a history of ocular surgery, the overall PPV for uveitis was 61% (95% CI, 56%-66%). The PPVs for individual uveitis codes ranged from 0% to 100%, and 11 uveitis codes had a PPV exceeding 80%. Herpes zoster ophthalmicus and scleritis/episcleritis ICD-9 codes had PPVs of 91% (95% CI, 86%-95%) and 60% (95% CI, 54%-66%), respectively. CONCLUSIONS AND RELEVANCE: Our results suggest that using ICD-9 codes alone to capture uveitis and scleritis/episcleritis diagnoses is not sufficient in the Kaiser Permanente Hawaii healthcare system, although there were specific uveitis codes with high PPVs. However, the electronic medical record can reliably be used to identify herpes zoster ophthalmicus cases. Medical record review, as was done in this study, is recommended to elucidate diagnoses for uveitis and scleritis/episcleritis. PMID- 27387136 TI - Analysis of the Intrinsically Disordered N-Terminus of the DNA Junction-Resolving Enzyme T7 Endonuclease I: Identification of Structure Formed upon DNA Binding. AB - The four-way (Holliday) DNA junction of homologous recombination is processed by the symmetrical cleavage of two strands by a nuclease. These junction-resolving enzymes bind to four-way junctions in dimeric form, distorting the structure of the junction in the process. Crystal structures of T7 endonuclease I have been determined as free protein, and the complex with a DNA junction. In neither crystal structure was the N-terminal 16-amino acid peptide visible, yet deletion of this peptide has a marked effect on the resolution process. Here we have investigated the N-terminal peptide by inclusion of spin-label probes at unique sites within this region, studied by electron paramagnetic resonance. Continuous wave experiments show that these labels are mobile in the free protein but become constrained on binding a DNA junction, with the main interaction occurring for residues 7-10 and 12. Distance measurements between equivalent positions within the two peptides of a dimer using PELDOR showed that the intermonomeric distances for residues 2-12 are long and broadly distributed in the free protein but are significantly shortened and become more defined on binding to DNA. These results suggest that the N-terminal peptides become more organized on binding to the DNA junction and nestle into the minor grooves at the branchpoint, consistent with the biochemical data indicating an important role in the resolution process. This study demonstrates the presence of structure within a protein region that cannot be viewed by crystallography. PMID- 27387137 TI - Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments. AB - Diketopyrrolopyrroles (DPP) are a relatively new class of organic high performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m(3) as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID- 27387138 TI - Crossmodal plasticity in auditory, visual and multisensory cortical areas following noise-induced hearing loss in adulthood. AB - Complete or partial hearing loss results in an increased responsiveness of neurons in the core auditory cortex of numerous species to visual and/or tactile stimuli (i.e., crossmodal plasticity). At present, however, it remains uncertain how adult-onset partial hearing loss affects higher-order cortical areas that normally integrate audiovisual information. To that end, extracellular electrophysiological recordings were performed under anesthesia in noise-exposed rats two weeks post-exposure (0.8-20 kHz at 120 dB SPL for 2 h) and age-matched controls to characterize the nature and extent of crossmodal plasticity in the dorsal auditory cortex (AuD), an area outside of the auditory core, as well as in the neighboring lateral extrastriate visual cortex (V2L), an area known to contribute to audiovisual processing. Computer-generated auditory (noise burst), visual (light flash) and combined audiovisual stimuli were delivered, and the associated spiking activity was used to determine the response profile of each neuron sampled (i.e., unisensory, subthreshold multisensory or bimodal). In both the AuD cortex and the multisensory zone of the V2L cortex, the maximum firing rates were unchanged following noise exposure, and there was a relative increase in the proportion of neurons responsive to visual stimuli, with a concomitant decrease in the number of neurons that were solely responsive to auditory stimuli despite adjusting the sound intensity to account for each rat's hearing threshold. These neighboring cortical areas differed, however, in how noise induced hearing loss affected audiovisual processing; the total proportion of multisensory neurons significantly decreased in the V2L cortex (control 38.8 +/- 3.3% vs. noise-exposed 27.1 +/- 3.4%), and dramatically increased in the AuD cortex (control 23.9 +/- 3.3% vs. noise-exposed 49.8 +/- 6.1%). Thus, following noise exposure, the cortical area showing the greatest relative degree of multisensory convergence transitioned ventrally, away from the audiovisual area, V2L, toward the predominantly auditory area, AuD. Overall, the collective findings of the present study support the suggestion that crossmodal plasticity induced by adult-onset hearing impairment manifests in higher-order cortical areas as a transition in the functional border of the audiovisual cortex. PMID- 27387139 TI - Applying Mathematical Optimization Methods to an ACT-R Instance-Based Learning Model. AB - Computational models of cognition provide an interface to connect advanced mathematical tools and methods to empirically supported theories of behavior in psychology, cognitive science, and neuroscience. In this article, we consider a computational model of instance-based learning, implemented in the ACT-R cognitive architecture. We propose an approach for obtaining mathematical reformulations of such cognitive models that improve their computational tractability. For the well-established Sugar Factory dynamic decision making task, we conduct a simulation study to analyze central model parameters. We show how mathematical optimization techniques can be applied to efficiently identify optimal parameter values with respect to different optimization goals. Beyond these methodological contributions, our analysis reveals the sensitivity of this particular task with respect to initial settings and yields new insights into how average human performance deviates from potential optimal performance. We conclude by discussing possible extensions of our approach as well as future steps towards applying more powerful derivative-based optimization methods. PMID- 27387140 TI - Ab initio engineering of materials with stacked hexagonal tin frameworks. AB - The group-IV tin has been hypothesized to possess intriguing electronic properties in an atom-thick hexagonal form. An attractive pathway of producing sizable 2D crystallites of tin is based on deintercalation of bulk compounds with suitable tin frameworks. Here, we have identified a new synthesizable metal distannide, NaSn2, with a 3D stacking of flat hexagonal layers and examined a known compound, BaSn2, with buckled hexagonal layers. Our ab initio results illustrate that despite being an exception to the 8-electron rule, NaSn2 should form under pressures easily achievable in multi-anvil cells and remain (meta)stable under ambient conditions. Based on calculated Z2 invariants, the predicted NaSn2 may display topologically non-trivial behavior and the known BaSn2 could be a strong topological insulator. PMID- 27387141 TI - Environmentally Optimal, Nutritionally Aware Beef Replacement Plant-Based Diets. AB - Livestock farming incurs large and varied environmental burdens, dominated by beef. Replacing beef with resource efficient alternatives is thus potentially beneficial, but may conflict with nutritional considerations. Here we show that protein-equivalent plant based alternatives to the beef portion of the mean American diet are readily devisible, and offer mostly improved nutritional profile considering the full lipid profile, key vitamins, minerals, and micronutrients. We then show that replacement diets require on average only 10% of land, 4% of greenhouse gas (GHG) emissions, and 6% of reactive nitrogen (Nr) compared to what the replaced beef diet requires. Applied to 320 million Americans, the beef-to-plant shift can save 91 million cropland acres (and 770 million rangeland acres), 278 million metric ton CO2e, and 3.7 million metric ton Nr annually. These nationwide savings are 27%, 4%, and 32% of the respective national environmental burdens. PMID- 27387142 TI - beta-glucuronidase mRNA levels are correlated with gait and working memory in premutation females: understanding the role of FMR1 premutation alleles. AB - Fragile X tremor ataxia syndrome (FXTAS) is a late-onset disorder manifesting in a proportion of FMR1 premutation individuals (PM: 55-199 CGG triplet expansions). FXTAS is associated with elevated levels of FMR1 mRNA which are toxic. In this study, relationships between neurocognitive and intra-step gait variability measures with mRNA levels, measured in blood samples, were examined in 35 PM and 35 matched control females. The real-time PCR assays measured FMR1 mRNA, and previously used internal control genes: beta-Glucuronidase (GUS), Succinate Dehydrogenase 1 (SDHA) and Eukaryotic Translation Initiation Factor 4A (EI4A2). Although there was significant correlation of gait variability with FMR1 mRNA levels (p = 0.004) when normalized to GUS (FMR1/GUS), this was lost when FMR1 was normalized to SDHA and EI4A2 (2IC). In contrast, GUS mRNA level normalized to 2IC showed a strong correlation with gait variability measures (p < 0.007), working memory (p = 0.001) and verbal intelligence scores (p = 0.008). PM specific changes in GUS mRNA were not mediated by FMR1 mRNA. These results raise interest in the role of GUS in PM related disorders and emphasise the importance of using appropriate internal control genes, which have no significant association with PM phenotype, to normalize FMR1 mRNA levels. PMID- 27387143 TI - New anticoagulants in cancer patient treatments. AB - Venous thromboembolism (VTE) is a common complication of cancer patients. Initiation of anticoagulant treatment is of vital importance once a diagnosis of VTE has been established. Unfractionated heparin and low-molecular-weight heparins (LMWH) have been the mainstay for in-hospital-based prophylaxis, both postsurgically and on medicine floors, and for the acute management of VTE. The current international guidelines, including American Society of Clinical Oncology, the American College of Chest Physicians, the European Society of Medical Oncology, and the International Society of Thrombosis and Hemostasis, recommend the use of LMWH monotherapy for the long-term management of cancer patients with established acute symptomatic VTE. Although LMWHs have become the preferred treatment for patients with cancer, problems with its use have prompted clinicians to seek newer antithrombotic agents. PMID- 27387144 TI - Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision. AB - The management of adenocarcinoma of the rectum is a dynamic field in oncology. The multidisciplinary approach to the management of this disease continues to evolve in each segment of its trimodality treatment. New scheduling regimens and radiosensitizing agents continue to emerge. Although total mesorectal excision continues to be the operation of choice for rectal cancers, what is done before and after surgery continues to evolve to maximize an ideal oncologic outcome with minimal morbidity. The achievement of a pathological complete response [pCR (i.e. ypT0N0)] in a fraction of patients undergoing neoadjuvant chemoradiation poses an interesting management dilemma. The cohort of patients who can achieve a pCR have superior oncologic outcomes compared to nonresponders. The present review addresses the need for adjuvant therapy in patients with a pCR. We discuss the evolution of the role of adjuvant therapy in patients with rectal cancer and the studies addressing the elimination of this strategy in all patients with rectal cancer with a goal of determining the current evidence that might result in the omission of adjuvant therapy for patients with ypT0N0 rectal cancer after chemoradiation and total mesorectal excision. PMID- 27387145 TI - Soldiers injured in Iraq War were let down by lack of dedicated health facilities, Chilcot report finds. PMID- 27387146 TI - Optimal Feedback Controlled Assembly of Perfect Crystals. AB - Perfectly ordered states are targets in diverse molecular to microscale systems involving, for example, atomic clusters, protein folding, protein crystallization, nanoparticle superlattices, and colloidal crystals. However, there is no obvious approach to control the assembly of perfectly ordered global free energy minimum structures; near-equilibrium assembly is impractically slow, and faster out-of-equilibrium processes generally terminate in defective states. Here, we demonstrate the rapid and robust assembly of perfect crystals by navigating kinetic bottlenecks using closed-loop control of electric field mediated crystallization of colloidal particles. An optimal policy is computed with dynamic programming using a reaction coordinate based dynamic model. By tracking real-time stochastic particle configurations and adjusting applied fields via feedback, the evolution of unassembled particles is guided through polycrystalline states into single domain crystals. This approach to controlling the assembly of a target structure is based on general principles that make it applicable to a broad range of processes from nano- to microscales (where tuning a global thermodynamic variable yields temporal control over thermal sampling of different states via their relative free energies). PMID- 27387147 TI - Reappraisal of the posterior approach for cervical decompressive herniectomy. AB - BACKGROUND: Does posterior cervical herniectomy impact on symptoms related to cervical paramedian/lateral soft disc herniation? METHODS: In a patient series over 15 years operated for single level paramedian/lateral soft disc herniation with posterior cervical approach, perceived radicular and cervical pre- and post operative symptoms were reconstructed and analyzed. RESULTS: Out of 105 patients with these characteristics 75 could be recruited for long-term follow-up. Preoperative symptoms included: radicular motor deficit (81.3%); radicular pain (93.3%); radicular sensory deficit (84%); cervical pain (80%) and disturbance of cervical motility (49.3%). Postoperatively radicular motor score improved in all patients (score 5 in 92% and 4 in 8%); sensory disturbance improved in all and radicular pain disappeared in 90% and improved in the others. Cervical pain disappeared in 78% and improved in other 22%, two had new onset moderate cervical pain. CONCLUSION: This series confirms safety and efficacy of the posterior approach in relieving motor and sensory symptoms in patients with symptomatic single level, lateral soft disc herniation. PMID- 27387149 TI - Highly Fluorinated Ir(III)-2,2':6',2"-Terpyridine-Phenylpyridine-X Complexes via Selective C-F Activation: Robust Photocatalysts for Solar Fuel Generation and Photoredox Catalysis. AB - A series of fluorinated Ir(III)-terpyridine-phenylpyridine-X (X = anionic monodentate ligand) complexes were synthesized by selective C-F activation, whereby perfluorinated phenylpyridines were readily complexed. The combination of fluorinated phenylpyridine ligands with an electron-rich tri-tert-butyl terpyridine ligand generates a "push-pull" force on the electrons upon excitation, imparting significant enhancements to the stability, electrochemical, and photophysical properties of the complexes. Application of the complexes as photosensitizers for photocatalytic generation of hydrogen from water and as redox photocatalysts for decarboxylative fluorination of several carboxylic acids showcases the performance of the complexes in highly coordinating solvents, in some cases exceeding that of the leading photosensitizers. Changes in the photophysical properties and the nature of the excited states are observed as the compounds increase in fluorination as well as upon exchange of the ancillary chloride ligand to a cyanide. These changes in the excited states have been corroborated using density functional theory modeling. PMID- 27387148 TI - A heavy metal P-type ATPase OsHMA4 prevents copper accumulation in rice grain. AB - Rice is a major source of calories and mineral nutrients for over half the world's human population. However, little is known in rice about the genetic basis of variation in accumulation of copper (Cu), an essential but potentially toxic nutrient. Here we identify OsHMA4 as the likely causal gene of a quantitative trait locus controlling Cu accumulation in rice grain. We provide evidence that OsHMA4 functions to sequester Cu into root vacuoles, limiting Cu accumulation in the grain. The difference in grain Cu accumulation is most likely attributed to a single amino acid substitution that leads to different OsHMA4 transport activity. The allele associated with low grain Cu was found in 67 of the 1,367 rice accessions investigated. Identification of natural allelic variation in OsHMA4 may facilitate the development of rice varieties with grain Cu concentrations tuned to both the concentration of Cu in the soil and dietary needs. PMID- 27387150 TI - Kinetic Models of Cyclosporin A in Polar and Apolar Environments Reveal Multiple Congruent Conformational States. AB - The membrane permeability of cyclic peptides and peptidomimetics, which are generally larger and more complex than typical drug molecules, is likely strongly influenced by the conformational behavior of these compounds in polar and apolar environments. The size and complexity of peptides often limit their bioavailability, but there are known examples of peptide natural products such as cyclosporin A (CsA) that can cross cell membranes by passive diffusion. CsA is an undecapeptide with seven methylated backbone amides. Its crystal structure shows a "closed" twisted beta-pleated sheet conformation with four intramolecular hydrogen bonds that is also observed in NMR measurements of CsA in chloroform. When binding to its target cyclophilin, on the other hand, CsA adopts an "open" conformation without intramolecular hydrogen bonds. In this study, we attempted to sample the complete conformational space of CsA in chloroform and in water by molecular dynamics simulations in order to better understand its conformational behavior in these two environments and to rationalize the good membrane permeability of CsA observed experimentally. From 10 MUs molecular dynamics simulations in each solvent, Markov state models were constructed to characterize the metastable conformational states. The model in chloroform is compared to nuclear Overhauser effect NMR spectroscopy data reported in this study and taken from the literature. The conformational landscapes in the two solvents show significant overlap but also clearly distinct features. PMID- 27387152 TI - The teleost head kidney: Integrating thyroid and immune signalling. AB - The head kidney, analogous to the mammalian adrenal gland, is an organ unique for teleost fish. It comprises cytokine-producing lymphoid cells from the immune system and endocrine cells secreting cortisol, catecholamines, and thyroid hormones. The intimate organization of the immune system and endocrine system in one single organ makes bidirectional signalling between these possible. In this review we explore putative interactions between the thyroid and immune system in the head kidney. We give a short overview of the thyroid system, and consider the evidence for the presence of thyroid follicles in the head kidney as a normal, healthy trait in fishes. From mammalian studies we gather data on the effects of three important pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-6) on the thyroid system. A general picture that emerges is that pro-inflammatory cytokines inhibit the activity of the thyroid system at different targets. Extrapolating from these studies, we suggest that the interaction of the thyroid system by paracrine actions of cytokines in the head kidney is involved in fine-tuning the availability and redistribution of energy substrates during acclimation processes such as an immune response or stress response. PMID- 27387151 TI - Involvement of a versatile pattern recognition receptor, apolipophorin-III in prophenoloxidase activation and antibacterial defense of the Chinese oak silkworm, Antheraea pernyi. AB - Apolipophorin-III (apoLp-III) is an exchangeable apolipoprotein found in many insect species and functions as a lipid transport vehicle. Recent studies have shown that apoLp-III is a multifunctional molecule involved in not only lipid transportation but also innate immune responses. In the present study, the pattern recognition properties of Antheraea pernyi apoLp-III were investigated. Recombinant Ap-apoLp-III was bound to different species of microbes and further study showed the rAp-apoLp-III is capable of interacting with pathogen associated molecular patterns (PAMPs) on the microbial cell surface. In addition, an Ap apoLp-III/PAMP mixture stimulated the prophenoloxidase (PPO) activation of A. pernyi hemolymph in vitro, to a greater extent than PAMP alone while Ap-apoLp-III itself failed to activate the PPO system, indicating that Ap-apoLp-III up regulates PPO activation by combining with PAMP. After pathogen invasion following an injection of Staphylococcus aureus, RNAi-mediated silencing of apoLp III decreased the transcriptional abundance of three antimicrobial peptide genes. These data suggest that apoLp-III is a versatile pattern recognition receptor and may play important roles in the innate immune responses of Antheraea pernyi. PMID- 27387153 TI - Amphibian immunity-stress, disease, and climate change. AB - Like all other vertebrate groups, amphibian responses to the environment are mediated through the brain (hypothalamic)-pituitary-adrenal/interrenal (HPA/I) axis and the sympathetic nervous system. Amphibians are facing historically unprecedented environmental stress due to climate change that will involve unpredictable temperature and rainfall regimes and possible nutritional deficits due to extremes of temperature and drought. At the same time, amphibians in all parts of the world are experiencing unprecedented declines due to the emerging diseases, chytridiomycosis (caused by Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans) and ranavirus diseases due to viruses of the genus Ranavirus in the family Iridoviridae. Other pathogens and parasites also afflict amphibians, but here I will limit myself to a review of recent literature linking stress and these emerging diseases (chytridiomycosis and ranavirus disease) in order to better predict how environmental stressors and disease will affect global amphibian populations. PMID- 27387154 TI - Aggregation of 12-Hydroxystearic Acid and Its Lithium Salt in Hexane: Molecular Dynamics Simulations. AB - 12-Hydroxystearic acid (12HSA) is a well-known organogelator, and its metal salts and derivatives find roles in many important applications. The structures of aggregates of 12-hydroxysteric acid and its salts depend sensitively on cation type, but a fundamental understanding of this phenomenon is lacking. In this study, molecular dynamics simulations were conducted on the microsecond long time scales for (1) 12HSA and (2) its lithium salt, each at 12.5 wt % in explicit hexane solvent. Self-assembly was accelerated by using a modified potential to prohibit alkane chain dihedral gauche states (all-trans-12HSA) and then verified by continuation using standard force-field parameters. In three independent simulation, acceleration using "gauche-less" potentials resulted in self assembled pseudocrystalline aggregates through formation of polarized five- and six-membered rings between inter-12-hydroxyl groups and head-to-head carboxylic acid dimerization. When subjected to the unmodified dihedral potential, two of the three structures remained stable after 1 MUs of MD. Stable structures exhibited a "ring-of-rings" motif, composed of two six-membered acetic acid dimerized ring bundles with six satellite rings, while the unstable structure did not. In strong contrast, the lithium salt produced a network of fibrils that spanned the volume of the sample. When lithium ions were substituted for carboxylic acid protons in the stable acid structures, they remained intact but lost their chiral nature. Both the acid and lithium structures displayed scattering peaks that agreed with experiment. Taken together, our results suggest that this ring-of-rings structure could be a primary feature of the self-assembly of 12HSA in organic solvents. PMID- 27387155 TI - SPECT/CT bone scintigraphy to evaluate low back pain in young athletes: common and uncommon etiologies. AB - Low back pain of various etiologies is a common clinical presentation in young athletes. In this article, we discuss the utility of SPECT/CT bone scintigraphy for the evaluation of low back pain in young athletes. The spectrum of lower spine lesions caused by sports injuries and identifiable on bone scan is presented along with strategies to avoid unnecessary irradiation of young patients. Also covered are pitfalls in diagnosis due to referred-pain phenomenon and normal skeletal variants specific to this age group. PMID- 27387156 TI - Reimagining Our Relationships with Patients: A Perspective from the Keystone IV Conference. AB - Substantial efforts to redesign health care delivery are underway in the United States, including primary care, without attention to what has historically been known as "the personal physician." The American Board of Family Medicine Foundation convened the Keystone IV Conference to reflect on the nature of personal doctoring and particularly what promises personal physicians might appropriately make and keep with their patients, going forward in new systems of care. This commentary describes the conference and its participants and provides an overview of manuscripts prepared by attendees that together comprise a written record of the conference. The authors conclude that a properly prepared and positioned personal physician practicing within a modernized primary care platform is a critical means of achieving better health and health care that is affordable, revitalizing the health professions workforce, and restoring population health in the United States. There is urgency to join with patients and colleagues to create the conditions under which people can have a personal physician of their choosing who knows them well, will stick with them as they wish, and be accountable for their receiving care that is appropriate for them as unique persons, with particular goals, preferences, and capabilities. PMID- 27387157 TI - G. Gayle Stephens and Wrestling the Bear: A Perspective from the Keystone IV Conference. PMID- 27387158 TI - Recharging Family Medicine: A Perspective from the Keystone IV Conference. AB - A historic perspective of family medicine's development, the work of Gayle Stephens, and prior Keystone conferences constitute an important backdrop for the fourth Keystone Conference. Decisions made in the past constrain what can be done now, but they may also offer opportunities for family medicine. A major challenge for Keystone IV was to discern what is a constraint and what is an opportunity-in particular when it comes to the role of the personal physician. This article provides reflections based on decades of observation and study and confirms that knowing something and doing something are not the same. PMID- 27387159 TI - Unfilled Hunger: Seeking Relationships in Primary Care-A Perspective from the Keystone IV Conference. AB - Family physicians hunger in a time of excess. This article reviews the importance of healing relationships in the craft of family medicine and several of the forces that have undermined the ability to achieve effective healing relationships. Several directions forward are recommended and a promise shared. PMID- 27387160 TI - Changing Places: Where Will We Be with Our Patients? A Perspective from the Keystone IV Conference. AB - Dr. Stephens knew a lot about place-his place within family medicine and the place of family medicine as a catalyst for change in our communities. In "G. Gayle Stephen's Festschrift," the evolution of our profession is mirrored by Dr. Stephen's seminal contributions to practice and service to his discipline. He describes our place as healers, teachers, scholars, builders, moral agents, professionals, and reformers. Stephen's place-changing career and ethos pave the way for our place as advocates for our patients and change agents for family medicine in this newest millennium. PMID- 27387161 TI - The Time of Our Lives: A Perspective from the Keystone IV Conference. AB - We often experience time as a commodity-in excess for those who suffer; in scarcity for those who minister to them. But it is also a teacher, a tool, and a generous yardstick for measuring one's career-if we take the time to reflect on it. This is an essay about time and timing as a doctor negotiates the practice of medicine. PMID- 27387162 TI - Holding On and Letting Go: A Perspective from the Keystone IV Conference. AB - This commentary examines what it might look like to be countercultural in the current era of health care change, and asks what we should hold onto and what we should let go of as we reinvent an ideal that gives meaning to family physicians and value to patients and populations - that primary health care is a relationship to be nurtured and supported, not just a commodity to be delivered and optimized, measured and incentivized, bought and sold. PMID- 27387163 TI - People Are Primary: A Perspective from the Keystone IV Conference. AB - As a person invested in personal doctoring, what promises are you willing to make about when and where you will "be there" for others? Attendees of the G. Gayle Stephens Keystone IV Conference answered that question on submitted index cards and through ongoing conference discussions. Those data were analyzed using grounded theory and combined to develop the following answer in aggregate: We will be held accountable to those who need us. We understand the need for expertise and compassion as we help others to navigate the intersection of science and humanism. We will serve as leaders in personal, public, and political conversations. We will mark a path for the profession ensuring alignment of personal practices with professional principles. We will not allow the needed conversations of processes, data points, and determinations of value to undermine our relationships with our patients. We will be there for you. Attentive and fully present. We will care for you when you have no need and you do not ask. We will center that care in your lived experience of health and illness, knowing you over time. We will be here for you now, over time and across distance, in ways that foster the feeling of wholeness and belonging. We will use the best knowledge, best tailored to meet our shared understanding of your goals and aspirations. PMID- 27387164 TI - A Countercultural Heritage: Rediscovering the Relationship-Centered and Social Justice Roots of Family Medicine-A Perspective from the Keystone IV Conference. AB - The 2015 G. Gayle Stephens Keystone conference convened a cohort of primary care professionals to discuss what promises personal physicians will make to their patients going forward. New physicians were prompted to rediscover the foundational values of and historic context for family medicine. At the heart of this rediscovery was learning of the writings and teachings of Dr. G. Gayle Stephens, a founder of family medicine who emphasized the essentiality of relationship-centered care and social justice to the new specialty. Dr. Stephens viewed family medicine as being in a countercultural relationship to mainstream medicine, as family medicine fought for justice and equity in an inequitable and fragmented health care system. Here we argue that by reaffirming and renewing this countercultural heritage the new generation of family physicians will have better clarity in approaching the many challenges in health care today. Particularly for trainees and new physicians, the historic lens offered by Dr. Stephens's writing and other foundational documents allows us to better see ourselves in a trajectory of ongoing health care reform. PMID- 27387165 TI - The Generation in Between: A Perspective from the Keystone IV Conference. AB - Keystone IV affirmed the value of relationships in family medicine, but each generation of family physicians took away different impressions and lessons. "Generation III," between the Baby Boomers and Millennials, reported conflict between their professional ideal of family medicine and the realities of current practice. But the Keystone conference also helped them appreciate core values of family medicine, their shared experience, and new opportunities for leadership. PMID- 27387166 TI - Patient Relationships and the Personal Physician in Tomorrow's Health System: A Perspective from the Keystone IV Conference. AB - A group of senior leaders from the early generation of academic family medicine reflect on the meaning of being a personal physician, based on their own clinical experiences and as teachers of residents and students in academic health centers. Recognizing that changes in clinical care and education at national and local systems levels have added extraordinary demands to the role of the personal physician, the senior group offers examples of how the discipline might go forward in changing times. Differently organized care such as the Family Health Team model in Ontario, Canada; value-based payment for populations in large health systems; and federal changes in reimbursement for populations can have positive effects on physician satisfaction. These changes and examples of changes in medical student and residency education also have the potential to positively affect the primary care workforce. The authors conclude that, without substantive educational and health system reform, the ability to truly serve as a personal physician and adhere to the values of continuity, responsibility, and accountability will continue to be threatened. PMID- 27387167 TI - Accelerating Momentum Toward Improved Health for Patients and Populations: Family Medicine as a Disruptive Innovation-A Perspective from the Keystone IV Conference. AB - This paper was prepared in follow up to the G. Gayle Stephens Keystone IV Conference by authors who attended the conference and are also members of the Family Medicine for America's Health board of directors (FMAHealth.org). It connects the aspirations of the current strategic and communications efforts of FMAHealth with the ideas developed at the conference. The FMAHealth project is sponsored by 8 national family medicine organizations and seeks to build on the work of the original Future of Family Medicine project. Among its objectives are a robust family physician workforce practicing in a continually improving medical home model, supported by a comprehensive payment model sufficient to sustain the medical home and enable the personal physician relationship with patients. PMID- 27387168 TI - The Personal Doctoring Manifesto: A Perspective from the Keystone IV Conference. AB - The Keystone IV Conference was a touchstone moment for multigenerational conversations regarding our health care system and an opportunity to reconnect with the values of personal doctoring as a vocation. It inspired participants to renew commitments to relationships, healthy communities, and social change. Keystone IV was also a stark reminder of the need to rekindle family medicine's counterculture flame in today's tumultuous health care environment and reclaim the role of personal doctors in American society. Reimagining and reigniting the fire of personal relationship is today's counterculture movement for primary care. Personal doctors must heed the call for immediate action, which requires defining when relationships matter most in health care and understanding how to harness paradigm shifts in information technology, team-based care, and population health to strengthen, rather than undermine, personal doctoring. Simultaneously, we must also invent a new notion of personal doctoring that creates partnerships with patients and families to drive forward a social movement demanding health care focused on the whole person in the context of his or her community. Change will occur when patients insist on a personal doctoring approach as an essential priority for what they expect from the health care system-that anything less is unacceptable. PMID- 27387169 TI - Social Justice as the Moral Core of Family Medicine: A Perspective from the Keystone IV Conference. AB - A recurring conference theme was the essential place of social justice within family medicine, especially the need to focus on denominator populations, exalt the personal and caring qualities of doctoring, and address social determinants of health. Many expressed solidarity with "community," but it is not always easy to define community in our large and diverse nation. Exhortations for health advocacy were frequently voiced, but putting these into meaningful action agendas is a challenge. There was general agreement that medicine is in flux and that the many expressions of "commodity-centered consumerism" have altered organization and financing. The increasing demands by "consumers", who want low cost, instant availability, and shared decision-making, and yet change doctors when health plans alter coverage also differentially impact high-volume, low-margin specialties such as family medicine. Additional challenges were the electronic health record and calibrating an appropriate work/life balance. Five action steps are recommended: 1) speak out on the important social and moral issues; 2) be the experts on personal care; 3) make common cause with potential allies; 4) help institutions perceive the value of generalism; and 5) help find ways to enrich generalist disciplines to increase the joy of medicine and decrease the threat of burn out. PMID- 27387170 TI - Exploring Variation in Known Pharmacogenetic Variants and its Association with Drug Response in Different Mexican Populations. AB - PURPOSE: Information on genetic variants that affect the pharmacokinetics and pharmacodynamics (PK/PD) of drugs in different populations from Mexico is still an ongoing endeavor. Here, we investigate allele frequencies on pharmacogenetic targets in Mexican Mestizos and Natives from three different States and its association with drug efficacy in individuals receiving either anticoagulants or antipsychotic drugs. METHODS: Natives from three different states and Mestizo patients receiving acenocoumarol or antipsychotics were genotyped using the DMET microarray (Affymetrix). RESULTS: We provide a collection of genetic variants that indicate that there are 3-times more variation than similarities between populations from Mexico and major continental groups. These differences were observed in several relevant targets including ABCB1, SLCO1A1, NAT2, UGTs, TYMS, VKORC1, and NR1I3. Moreover, Mexican Mestizos also showed allele frequency differences when compared to Natives for variants on DPYD, ADH1A, CYP3A4, SLC28A3, and SLC28A1. Significant allele differences also arose among the three Native groups here studied, mostly for transporters of the ABC-binding cassette and the solute carrier gene family. Finally, we explored genotype-drug response associations and pinpointed variants on FMOs (coumarins), and GSTM1 (haloperidol). CONCLUSIONS: These findings confirm previous results and further delve into the pharmacogenetics of Mexican populations including different Native groups. PMID- 27387171 TI - An Assessment of the Permeation Enhancer, 1-phenyl-piperazine (PPZ), on Paracellular Flux Across Rat Intestinal Mucosae in Ussing Chambers. AB - PURPOSE: 1-phenyl piperazine (PPZ) emerged from a Caco-2 monolayer screen as having high enhancement potential due to a capacity to increase permeation without significant toxicity. Our aim was to further explore the efficacy and toxicity of PPZ in rat ileal and colonic mucosae in order to assess its true translation potential. METHODS: Intestinal mucosae were mounted in Ussing chambers and apparent permeability coefficient (Papp) values of [(14)C]-mannitol and FITC-dextran 4 kDa (FD-4) and transepithelial electrical resistance (TEER) values were obtained following apical addition of PPZ (0.6-60 mM). Exposed issues were assessed for toxicity by histopathology and lactate dehydrogenase (LDH) release. Mucosal recovery after exposure was also assessed using TEER readings. RESULTS: PPZ reversibly increased the Papp of both agents across rat ileal and distal colonic mucosae in concentration-dependent fashion, accompanied by TEER reduction, with acceptable levels of tissue damage. The complex mechanism of tight junction opening was part mediated by myosin light chain kinase, stimulation of transepithelial electrogenic chloride secretion, and involved activation of 5-HT4 receptors. CONCLUSIONS: PPZ is an efficacious and benign intestinal permeation enhancer in tissue mucosae. However, its active pharmacology suggest that potential for further development in an oral formulation for poorly permeable molecules will be difficult. PMID- 27387172 TI - Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip. AB - BACKGROUND: The unsuccessful treatment of prosthetic joint infection (PJI) with two-stage revision leads to infection recurrence. The objectives of the study were to assess the clinical and demographic characteristics of patients with polymicrobial PJI, and to evaluate the role of the microbial profile involved in PJI in the risk of infection recurrence after the first step of two-stage revision surgery. MATERIALS AND METHODS: A retrospective analysis of 189 cases of culture-positive PJI following total hip replacement over a 5-year period was performed. The demographic characteristics of patients, clinical symptoms, microbiology cultures of intraoperative biopsies, laboratory values of C-reactive protein (CRP), white blood cell count and erythrocyte sedimentation rate were analyzed. Patients were divided into two groups-135 with monomicrobial and 54 with polymicrobial infection. RESULTS: Of all patients, 68.9 % in the monomicrobial and 83.3 % in the polymicrobial group had a body mass index >25 kg/m2 (p = 0.05). The median CRP values were 5.7 mg/L (IQR 4.0-10.0 mg/L) in the monomicrobial compared to 8.8 mg/L (IQR 5.0-27 mg/L) in the polymicrobial group (p = 0.01). The percentage of successful outcomes was 27.8 % in patients with microbial associations (p < 0.0001). Gram-negative pathogens caused polymicrobial PJI in 61.5 % of cases with infection recurrence (OR 4.4; 95 % CI 1.18-16.37; p = 0.03). CONCLUSIONS: Overweight and obese patients or those with elevated CRP had a greater risk of polymicrobial PJI. They were predisposed to recurrence of infection after the first step of two-stage revision. An unsuccessful outcome was more likely in cases with polymicrobial infection compared to those with monomicrobial infection. In addition, the presence of multidrug-resistant strains of Gram-negative bacteria substantially increased the risk of PJI treatment being unsuccessful. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27387173 TI - The surgical defect after transanal endoscopic microsurgery: open versus closed management. AB - BACKGROUND: To determine whether closure of the defect created during full thickness excision of a rectal lesion with transanal endoscopic microsurgery (TEM) leads to fewer complications when compared to leaving the defect unsutured. METHODS: This is a single-center cohort study using a prospectively maintained database. All patients >=18 years old treated with full thickness TEM with no compromise of the peritoneal cavity were included. Two cohorts were established: patients with the defect sutured and patients with the defect left open. Demographic, operative, and pathologic data were compared. The main outcome analyzed was early (<30 day postoperative) complications, including bleeding that required investigation and readmission, infection, and reoperation. RESULTS: Between 2007 and 2014, data for all patients treated with TEM have been maintained in the St. Paul's Hospital TEM database. Overall, 236 patients had the TEM defect sutured (TEM-S) and 105 patients had the defect left open (TEM-O). There were no differences between the groups in patient age, gender, tumor size or underlying tumor histology. There was no difference in OR time between the groups, but the most experienced TEM surgeon performed significantly more of the TEM-S procedures (61 vs. 39 %, p < 0.01). There were 40 postoperative complications, affecting 11.7 % of the cohort. The complication rate was higher in the TEM-O group (8.4 vs. 19.0 %, p = 0.03). There was no statistically significant difference in bleeding complications (4.7 vs. 7.6 %, p = 0.27) or infections (2.1 vs. 6.7 %, p = 0.05). Readmissions were less common in the TEM-S group (4.7 vs 12.4 %, p = 0.01). CONCLUSION: The St. Paul's Hospital TEM experience suggests that while it is safe to leave rectal defects open when a robust mesorectal fat layer is present, there appears to be fewer postoperative complications when the defect is sutured closed. PMID- 27387174 TI - Increased use of surgical energy promotes methicillin-resistant Staphylococcus aureus colonization in rabbits following open ventral hernia mesh repair. AB - BACKGROUND: Surgical energy has been widely implemented because of ease of use, effective hemostasis, and surgical dissection. Studies demonstrate its use to be an independent risk factor for postoperative wound infection. Methicillin resistant Staphylococcus aureus (MRSA) is the most common bacteria found in postoperative mesh infection. No reports are available on the sequelae of surgical energy use for open ventral hernia repair (oVHR) with mesh. We hypothesized that increasing amounts of surgical energy will result in higher infectious burden after oVHR with composite multifilament polyester mesh (ParietexTM PCO). METHODS: New Zealand rabbits underwent bridging oVHR with ParietexTM PCO and were divided into three surgical treatment groups: (1) scalpel alone, (2) 120 J of energy, and (3) 600 J of energy. The bioprosthesis was then inoculated with 105 colony-forming units of MRSA. Rabbits were survived for 7 days with daily physical examination. Complete blood count, basci metabolic panel, and blood cultures were performed on postoperative days one, four, and seven. Surviving rabbits were killed, and meshes explanted for MRSA colony counts. RESULTS: Rabbits receiving the most surgical energy developed signs and symptoms of severe sepsis and wound necrosis within 24 h. In comparison, rabbits receiving no surgical energy had significantly less MRSA recovered from explanted mesh, significantly less bacteremia, and fewer adhesions. CONCLUSIONS: Increased use of surgical energy promoted greater colonization, exaggerated septic response to bacterial contamination, and more severe adhesions. In the absence of devitalized tissue, rabbits can effectively limit bacterial contamination. These findings support the surgical principles of proper tissue handling and highlight the detrimental effects of indiscriminant surgical energy usage, thus emphasizing the importance of programs such as Fundamental Use of Surgical Energy. PMID- 27387175 TI - Techniques to perform robotic left adrenalectomy in the obese patient. AB - INTRODUCTION: Minimally invasive adrenalectomy may be associated with reduction in postoperative pain, morbidity, and length of stay and, as a result, has become a preferred approach for many adrenal tumors. Left-sided adrenal tumors, however, are particularly challenging to address in the morbidly obese patient due to difficulties in maintaining exposure and dissection. The robotic platform offers instruments with greater degrees of freedom that aid in retraction and dissection, especially of the adrenal vein, but fixed patient positioning and the large distance needed between patient ports to avoid arm collisions can be restrictive in patients with a large amount of retroperitoneal fat and small working space. METHODS/RESULTS: We demonstrate robotic left adrenalectomy (RLA) in a consecutive series of patients with a mean weight of 99 kg and mean BMI of 36. Techniques to safely and efficiently perform RLA in obese patients are stepwise demonstrated, including (1) Patient positioning, (2) Management of the pannus, (3) Customized port placement, (4) Medial retraction of the pancreas, (5) Finding the left adrenal vein, and (6) Management of bleeding. Intraoperative videos from multiple patients also show surgical pitfalls, examples of poor port placement, arm collisions, alternative approaches to the vein, and techniques to control unexpected bleeding. All patients in the series underwent successful RLA with negative margins, no major intra- or postoperative complications, and discharge on POD 1-2. CONCLUSION: Though poor exposure due to patient body habitus is a relative contraindication, even large left-sided adrenal tumors can be safely approached robotically while adhering to oncologic principles, as is demonstrated in this video. PMID- 27387176 TI - Erratum to: Laparoscopic resection of paraaortic/paracaval neurogenic tumors: surgical outcomes and technical tips. PMID- 27387177 TI - Erratum to: Laparoscopic hepatectomy by curettage and aspiration: a report of 855 cases. PMID- 27387178 TI - Erratum to: Strategies of laparoscopic thyroidectomy for treatment of substernal goiter via areola approach. PMID- 27387179 TI - Safety of endoscopic resection for duodenal subepithelial lesions with wound closure using clips and an endoloop: an analysis of 68 cases. AB - BACKGROUND: Endoscopic removal of a duodenal lesion is still considered to be a challenging procedure that can be fraught with potentially serious complications, specifically perforation or delayed bleeding. This study was to assess the safety of endoscopic resection for duodenal subepithelial lesions (SELs) with wound closure using clips and an endoloop. METHODS: From October 2010 to July 2015, a total of 68 consecutive patients with duodenal SELs were treated with endoscopic resection with wound closure using clips and an endoloop. The main outcome measures considered were the incidence of complete resection, perioperative perforation, delayed perforation, delayed bleeding, residual lesions, and lesion recurrence. RESULTS: Complete resection was successfully achieved for all 68 patients. The median lesion size was 1.7 cm. The median procedure time was 62 min. The mean hospital stay was 5.5 days. During the procedure, five patients developed perioperative perforations (7.4 %) and no patients developed delayed bleeding, delayed perforation, or other serious complications. The five patients with perioperative perforations recovered after conservative treatment. The perioperative perforation rate was significantly higher for lesions originating in the muscularis propria layer (18.2 %) than in the submucosal layer (2.2 %; p < 0.05). No residual or recurrent lesions were detected during the follow-up period (median: 27 months). CONCLUSIONS: Endoscopic resection with wound closure using clips and an endoloop is an effective and reasonably safe therapeutic method for treating/removing duodenal SELs when managed by an experienced endoscopic team, and it can provide an alternative treatment option for patients with duodenal SELs. PMID- 27387180 TI - Prone position in thoracoscopic esophagectomy improves postoperative oxygenation and reduces pulmonary complications. AB - BACKGROUND: While thoracoscopic esophagectomy is a widely performed surgical procedure, only few studies regarding the influence of body position on changes in circulation and breathing, after the surgery, have been reported. This study aimed at evaluating the effect of body position, during surgery, on the postoperative breathing functions of the chest. METHODS: A total of 266 patients who underwent right-sided transthoracic esophagectomy for esophageal cancer from 2004 to 2012 were included in this study. Fifty-four of them underwent open thoracotomies in the left lateral decubitus position (Group O), 108 underwent thoracoscopic esophagectomy in the left lateral decubitus position (Group L) and 104 patients were treated by thoracoscopic esophagectomy in the prone position (Group P). Two patients in Group P, who presented with intra-operative bleeding and underwent thoracotomy, were subsequently excluded from the pulmonary function analysis. RESULTS: Two patients in Group P had to be changed from the prone position to the lateral decubitus position and underwent thoracotomy in order to control intra-operative bleeding. Despite the significantly longer chest operation period in Group P, total blood loss was significantly lower in this group when compared to Groups O and L. Furthermore, patients in Group P presented with significantly lower water balance during the perioperative period and markedly higher SpO2/FiO2 ratio after the surgery. The incidence of respiratory complications was significantly higher in Group O when compared to the other two groups; however, no significant differences were observed between the Groups L and P. CONCLUSION: The findings of this study demonstrate that thoracoscopic esophagectomy in the prone position improves postoperative oxygenation and is therefore a potentially superior surgical approach. PMID- 27387181 TI - Portomesenteric vein thrombosis after laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass: a 36-case series. AB - BACKGROUND: Portomesenteric vein thrombosis following laparoscopic bariatric surgical procedures is a serious and potentially lethal complication. It is quite rare, and its clinical presentation, management, and sequelae remain poorly understood. METHODS: We searched PubMed, Medline, Google Scholar, Ovid, and Cochrane databases for articles reporting case series and systematic reviews in the English language on patients who underwent laparoscopic bariatric surgery and had a subsequent portal or mesenteric vein thrombosis. Articles discussing laparoscopic gastric banding were excluded. RESULTS: A total of 14 articles reporting on 36 cases were found. We analyzed the pooled data from these case reports and series with emphasis on number of reported patients, demographics, time of diagnosis, risk factors, symptoms, management, complications, and sequelae. CONCLUSIONS: Portomesenteric vein thrombosis is not uncommon following laparoscopic bariatric surgery and appears to occur more after laparoscopic sleeve gastrectomy. Bariatric surgeons should have a high index of suspicion for early detection and treatment of this potentially lethal complication. Obese patients at high risk for venous thrombosis should be screened for genetic predisposition for hypercoagulable state and should be considered for extended thromboprophylaxis postoperatively. PMID- 27387182 TI - High educational impact of a national simulation-based urological curriculum including technical and non-technical skills. AB - BACKGROUND: Although simulation training is increasingly used to meet modern technology and patient safety demands, its successful integration within surgical curricula is still rare. The Dutch Urological Practical Skills (D-UPS) curriculum provides modular simulation-based training of technical and non-technical basic urological skills in the local hospital setting. This study aims to assess the educational impact of implementing the D-UPS curriculum in the Netherlands and to provide focus points for improvement of the D-UPS curriculum according to the participants. METHODS: Educational impact was assessed by means of qualitative individual module-specific feedback and a quantitative cross-sectional survey among residents and supervisors. Twenty out of 26 Dutch teaching hospitals participated. The survey focussed on practical aspects, the D-UPS curriculum in general, and the impact of the D-UPS curriculum on the development of technical and non-technical skills. RESULTS: A considerable survey response of 95 % for residents and 76 % for supervisors was obtained. Modules were attended by junior and senior residents, supervised by a urologist, and peer teaching was used. Ninety percent of supervisors versus 67 % of residents judged the D-UPS curriculum as an important addition to current residency training (p = 0.007). Participants' aggregated general judgement of the modules showed a substantial percentage favorable score (M +/- SE: 57 +/- 4 %). The impact of training on, e.g., knowledge of materials/equipment and ability to anticipate on complications was high, especially for junior residents (77 +/- 5 and 71 +/- 7 %, respectively). Focus points for improvement of the D-UPS curriculum according to the participants include adaptation of the training level to residents' level of experience and focus on logistics. CONCLUSION: The simulation-based D-UPS curriculum has a high educational impact. Residents and supervisors consider the curriculum to be an important addition to current residency training. Focus points for improvement of the D-UPS curriculum according to the participants include increased attention to logistics and integration of a spiral learning approach. PMID- 27387183 TI - Diagnostic Usefulness of Claudin-3 and Claudin-4 for Immunocytochemical Differentiation between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks. AB - OBJECTIVE: Claudin-3 and claudin-4 have recently been reported as promising targets for the detection and diagnosis of cancer. This study was designed to evaluate the diagnostic value of claudin-3 and claudin-4 immunoreactivity to distinguish metastatic adenocarcinoma cells (MAC) from reactive mesothelial cells (RMC) in effusions. STUDY DESIGN: Claudin-3 and claudin-4 immunocytochemical staining was performed on 234 cell block specimens, including 194 malignant effusions with MAC and 40 benign effusions with RMC. Any degree of membranous staining was considered positive. RESULTS: Claudin-3 was positive in 190 (97.9%) out of 194 cases with MAC and in 3 (7.5%) out of 40 cases with RMC. Claudin-4 immunoreactivity was seen in all 194 (100%) cases with MAC and in 11 (27.5%) out of 40 cases with RMC. In all claudin-3- or claudin-4-positive RMC samples, the area of positive staining was <25% of the cells. Claudin-3 and claudin-4 efficiently discriminated between MAC and RMC (p < 0.001 for both), and claudin-3 was more specific than claudin-4 in differentiating between MAC and RMC (p < 0.05). CONCLUSION: These results suggest that claudin-3 and claudin-4 are good candidates to be included as MAC markers in the panel of antibodies to distinguish MAC from RMC in effusion specimens. PMID- 27387185 TI - [Not Available]. PMID- 27387184 TI - Management of primary spontaneous pneumothorax by intensivists: an international survey. PMID- 27387186 TI - General Anesthesia Versus Conscious Sedation in Acute Stroke Treatment: The Importance of Head Immobilization. AB - PURPOSE: While today mechanical thrombectomy is an established treatment option for main branch occlusions in anterior circulation stroke, there is still an ongoing debate on the kind of anesthesia to be preferred. Introducing a simple method for head stabilization, we analyzed safety and duration of endovascular recanalization procedures under general anesthesia (GA) and conscious sedation (CS). METHODS: We retrospectively identified 84 consecutive patients who underwent mechanical thrombectomy owing to acute anterior circulation stroke. Fifty-three were treated under GA and 31 under CS equipped with a standard cervical collar to reduce head movement. We evaluated recanalization results, in house time to start recanalization, procedure times, technical and clinical complication rates, and conversion rates from CS to GA. RESULTS: Recanalization of mTICI >=2b was achieved in 80 % under CS and in 81 % under GA. Median in-house time to start recanalization for CS was 60 min (IQR 28; 44-72) and 77 min (IQR 23; 68-91) for GA (P = 0.001). Median procedure time under CS was 35 min (IQR 43; 69-25) and 41 min (IQR 43; 66-23) for GA (P = 0.9). No major complications such as ICH occurred in either group, and no conversions from CS to GA were necessary. CONCLUSION: Mechanical thrombectomy can be performed faster and safely under CS in combination with simple head immobilization using a standard cervical collar. PMID- 27387187 TI - RF Ablation of Giant Hemangiomas Inducing Acute Renal Failure: A Report of Two Cases. AB - OBJECTIVE: In patients that require treatment for hepatic giant cavernous hemangiomas (GCH), radiofrequency ablation (RFA) has been suggested to represent a safe and effective alternative to invasive surgery. In a recent report of bipolar RFA, using two expandable needle electrodes, was uneventfully performed in patients with large GCH (>10 cm). The objective of this report is to present two cases in which bipolar RFA of symptomatic GCH was complicated by acute kidney injury. MATERIALS AND METHODS: In 2015 we treated two patients for very large symptomatic GCH (15.7 and 25.0 cm) with bipolar RFA during open laparotomy. RESULTS: In both patients the urine showed a red-brown discoloration directly after the ablation. They became anuric and presented with progressive dyspnea, tachypnea, and tachycardia, requiring hemodialysis for a period of 1 month in one case. Lab results revealed hemepigment-induced acute kidney. Both patients fully recovered and both showed a complete relief of symptoms at 3 months following the procedure. CONCLUSION: RFA for large GCHs can cause hemepigment-induced acute kidney injury due to massive intravascular hemolysis. The presented cases suggest that caution is warranted and advocate an upper limit regarding the volume of GCHs that can be safely ablated. PMID- 27387188 TI - MWA Versus RFA for Perivascular and Peribiliary CRLM: A Retrospective Patient- and Lesion-Based Analysis of Two Historical Cohorts. AB - PURPOSE: To retrospectively analyse the safety and efficacy of radiofrequency ablation (RFA) versus microwave ablation (MWA) in the treatment of unresectable colorectal liver metastases (CRLM) in proximity to large vessels and/or major bile ducts. METHOD AND MATERIALS: A database search was performed to include patients with unresectable histologically proven and/or (18)F-FDG-PET avid CRLM who were treated with RFA or MWA between January 2001 and September 2014 in a single centre. All lesions that were considered to have a peribiliary and/or perivascular location were included. Univariate logistic regression analysis was performed to assess the distribution of patient, tumour and procedure characteristics. Multivariate logistic regression was used to correct for potential confounders. RESULTS: Two hundred and forty-three patients with 774 unresectable CRLM were ablated. One hundred and twenty-two patients (78 males; 44 females) had at least one perivascular or peribiliary lesion (n = 199). Primary efficacy rate of RFA was superior to MWA after 3 and 12 months of follow-up (P = 0.010 and P = 0.022); however, after multivariate analysis this difference was non-significant at 12 months (P = 0.078) and vanished after repeat ablations (P = 0.39). More CTCAE grade III complications occurred after MWA versus RFA (18.8 vs. 7.9 %; P = 0.094); biliary complications were especially common after peribiliary MWA (P = 0.002). CONCLUSION: For perivascular CRLM, RFA and MWA are both safe treatment options that appear equally effective. For peribiliary CRLM, MWA has a higher complication rate than RFA, with similar efficacy. Based on these results, it is advised to use RFA for lesions in the proximity of major bile ducts. PMID- 27387189 TI - Monitoring temperature sensitivity of soil organic carbon decomposition under maize-wheat cropping systems in semi-arid India. AB - Long-term storage of soil organic carbon (SOC) is essential for sustainability of agricultural ecosystems and maintaining overall environment quality as soils contain a significant part of global carbon stocks. In this study, we attempted to explain the carbon mineralization and temperature sensitivity of SOC in maize wheat systems, a common cropping system in the semi-arid regions of India. Soil samples(0-0.15 m) from long-term experimental plots laid in split plot design with two tillage systems (conventional tillage and bed planting) and six nutrient management treatments (T 1 = control, T 2 = 120 kg urea-N/ha, T 3 = T2 (25 % N substituted by farmyard manure (FYM)), T 4 = T 2 (25 % N substituted by sewage sludge), T 5 = T 2 + crop residue, T 6 = 100 % recommended doses of N through organic source - 50 % FYM + 25 % biofertilizer + 25 % crop residue) were incubated at different temperatures (25, 30, 35, and 40 degrees C) to determine the thermal sensitivity parameters associated with carbon mineralization. Earlier reports suggest a selective preservation of C3-derived carbon fractions over C4 in the SOC pool, and this is the first instance where delta (13)C signatures (C4 derived carbon) were used as a qualitative measure to assess thermal sensitivity of SOC pools in the maize-wheat crop rotation systems of semi-arid India. Among the nutrient management treatments, mineral fertilizers were found to add more C4 derived carbon to the SOC pool in both the tillage systems but shows less promise in SOC stability as indicated by their lower activation energies (Ea) (14.25 kJ mol(-1)). Conventional tillage was found to mineralize 18.80 % (T 1-control at 25 degrees C) to 29.93 % carbon (T 3-mineral fertilizer + FYM at 40 degrees C) during the 150 days of incubation which was significantly higher than bed planting system (14.90 % in T 1-control at 25 degrees C and 21.99 % in T 6-100% organic sources at 40 degrees C). Organic manures, especially FYM (19.11 kJ mol( 1)) and 100 % organics (19.33 kJ mol(-1)) were more effective in enhancing the Ea of SOC than plots with mineral fertilizers alone (14.25 kJ mol(-1)), but had relatively higher Q 10 values thereby corroborating the thermal sensitivity hypothesis of recalcitrant organic compounds in soil. Michaelis-Menten derivatives along with thermal sensitivity indicators such as Ea and Q 10 were found to be efficient parameters for explaining carbon mineralization and CO2 efflux from soils. PMID- 27387190 TI - Changes in vegetation cover and composition in the Swedish mountain region. AB - Climate change, higher levels of natural resource demands, and changing land use will likely lead to changes in vegetation configuration in the mountain regions. The aim of this study was to determine if the vegetation cover and composition have changed in the Swedish region of the Scandinavian Mountain Range, based on data from the long-term landscape biodiversity monitoring program NILS (National Inventory of Landscapes in Sweden). Habitat type and vegetation cover were assessed in 1740 systematically distributed permanent field plots grouped into 145 sample units across the mountain range. Horvitz-Thompson estimations were used to estimate the present areal extension of the alpine and the mountain birch forest areas of the mountain range, the cover of trees, shrubs, and plants, and the composition of the bottom layer vegetation. We employed the data from two subsequent 5-year monitoring periods, 2003-2007 and 2008-2012, to determine if there have been any changes in these characteristics. We found that the extension of the alpine and the mountain birch forest areas has not changed between the inventory phases. However, the total tree canopy cover increased in the alpine area, the cover of graminoids and dwarf shrubs and the total cover of field vegetation increased in both the alpine area and the mountain birch forest, the bryophytes decreased in the alpine area, and the foliose lichens decreased in the mountain birch forest. The observed changes in vegetation cover and composition, as assessed by systematic data in a national and regional monitoring scheme, can validate the results of local studies, experimental studies, and models. Through benchmark assessments, monitoring data also contributes to governmental policies and land-management strategies as well as to directed cause and effect analyses. PMID- 27387191 TI - Unusual side effect of cannabis use: acute abdomen due to duodenal perforation. AB - BACKGROUND: The chronic use of synthetic cannabinoids (SCs) which has become an increasingly prevalent problem can rarely cause gastric and duodenal ulcer because of their effects on gastric secretion and emptying. Since peptic ulcer disease (PUD) is a rarely seen entity in patients who consult to the emergency service with complaints of abdominal pain, most of the physicians do not suspect of this clinical diagnosis. Perforation is a mortal complication of PUD, and early diagnosis and emergency surgery are life-saving procedures. CASE PRESENTATION: A 16-year-old male patient was referred to our emergency service from another center with abdominal distension, complaints of abdominal pain, and bilious vomiting. His medical history revealed that he had been regularly using bonsai for the past 3 years. Plain abdominal radiograms of standing position revealed subdiaphragmatic free air, then we performed laparotomy which disclosed perforation of the first part of the duodenum. Surgical intervention with omental patch and primary closure (Graham patch) was successful. The patient who underwent nasogastric decompression and received antibiotherapy had not experienced any complication during the postoperative follow-up period. CONCLUSION: Herein, as an unusual manifestation, a patient who developed duodenal perforation following chronic SC use has been reported. In adolescent patients admitted with PUD or its complications to the emergency services, it is important to inquire for the use of addictive substances which are increasingly prevalent in order to determine the etiology. PMID- 27387192 TI - Polypiperazine-amide Nanofiltration Membrane Modified by Different Functionalized Multiwalled Carbon Nanotubes (MWCNTs). AB - In this work, three modified multiwalled carbon nanotubes (MWCNTs) with carboxyl (MWCNT-COOH), hydroxyl (MWCNT-OH) and amino groups (MWCNT-NH), respectively, were added into the aqueous phase containing piperazine (PIP) to fabricate the nanocomposite nanofiltration (NF) membranes via interfacial polymerization. The influences of functional groups of MWCNTs on the performance of modified NF membrane were investigated. The MWCNTs were characterized by TEM, FT-IR and TGA; meanwhile, the properties of the membranes were evaluated by XPS, TEM, AFM and contact angle. The XPS results proved the successful incorporation of MWCNT in the active layer of modified NF membrane. When the MWCNT concentration is 0.01% (w/v), all the nanocomposite membranes possessed the optimal separation properties, among which the membrane incorporated with MWCNT-OH demonstrated the highest water flux of 41.4 L.m(-2).h(-1) and the Na2SO4 rejection of 97.6% whereas the one with MWCNT-COOH had the relative lowest rejection of 96.6%. Furthermore, the increased hydrophilicity of functional groups in modified MWCNTs resulted in different nodular surface morphologies, thicknesses and hydrophilicities of the nanocomposite membranes. All the membranes possessed a molecular weight cutoff (MWCO) within 300 Da and good operation stability. PMID- 27387193 TI - Posttraumatic Stress Disorder, Health Problems, and Depression Among African American Women in Residential Substance Use Treatment. AB - BACKGROUND: Rates of posttraumatic stress disorder (PTSD) are high among women seeking treatment for substance use disorders (SUDs). Minority women, in particular, experience high rates of trauma and may be less likely to disclose trauma history. This article identifies items from pre-existing screening measures that can be used across settings to sensitively but noninvasively identify women with likely PTSD. METHOD: For a sample of 104 African American women in residential SUD treatment who provided informed consent as a part of a larger randomized clinical trial, the prevalence of trauma and PTSD, as well as the relationships between trauma, health, depression, and distress, was examined. Measures included Posttraumatic Stress Diagnostic Scale (PDS), Center for Epidemiologic Studies-Depression Scale (CES-D), Pennebaker Inventory of Limbic Languidness (PILL), and Brief Symptom Inventory (BSI). Additional analyses were undertaken to determine if a subset of noninvasive items could serve to identify the presence of a probable PTSD diagnosis. RESULTS: Most women (94.2%) reported at least one lifetime trauma, with over half (51.0%) meeting DSM-IV criteria for PTSD. Women with greater trauma symptom severity reported more health problems and higher levels of depression and distress. Five BSI items and one CES-D item were significantly associated with a probable PTSD diagnosis with a sensitivity of 88.7%, a specificity of 66.7%, a positive predictive value of 73.4%, a negative predictive value of 85.0%, and an accuracy of 77.9%. CONCLUSION: Findings affirm that African American women with SUDs present for residential treatment with comorbid psychiatric and emotional conditions that warrant assessment and treatment. Results highlight potential benefits of brief screening with routine measures and coordinated access to ancillary psychiatric and medical services, in conjunction with substance treatment, such as in residential or primary care. PMID- 27387194 TI - TBC2health: a database of experimentally validated health-beneficial effects of tea bioactive compounds. AB - Tea is one of the most consumed beverages in the world. Considerable studies show the exceptional health benefits (e.g. antioxidation, cancer prevention) of tea owing to its various bioactive components. However, data from these extensively published papers had not been made available in a central database. To lay a foundation in improving the understanding of healthy tea functions, we established a TBC2health database that currently documents 1338 relationships between 497 tea bioactive compounds and 206 diseases (or phenotypes) manually culled from over 300 published articles. Each entry in TBC2health contains comprehensive information about a bioactive relationship that can be accessed in three aspects: (i) compound information, (ii) disease (or phenotype) information and (iii) evidence and reference. Using the curated bioactive relationships, a bipartite network was reconstructed and the corresponding network (or sub network) visualization and topological analyses are provided for users. This database has a user-friendly interface for entry browse, search and download. In addition, TBC2health provides a submission page and several useful tools (e.g. BLAST, molecular docking) to facilitate use of the database. Consequently, TBC2health can serve as a valuable bioinformatics platform for the exploration of beneficial effects of tea on human health. TBC2health is freely available at http://camellia.ahau.edu.cn/TBC2health. PMID- 27387195 TI - Minimum 5-year follow-up outcomes for single-stage transpedicular debridement, posterior instrumentation and fusion in the management of thoracic and thoracolumbar spinal tuberculosis in adults. AB - AIM: The aim of this retrospective clinical study is to evaluate the long-term outcomes for single-stage transpedicular debridement, posterior instrumentation and fusion in the management of thoracic and thoracolumbar spinal tuberculosis in adults. METHODS: Fifty-nine adult patients with thoracic and thoracolumbar spinal tuberculosis underwent single-stage transpedicular debridement, posterior instrumentation and fusion. These patients were followed for a minimum of 5 years. Patients were assigned to one of two groups according to the infected anatomic segment. In the thoracic spinal tuberculosis group, there were 28 cases (17 males, 11 females) with a mean age of 38.9 years; in the thoracolumbar spinal tuberculosis group, there were 31 cases (19 males, 12 females) with a mean age of 40.3 years. All cases were evaluated clinically using the visual analog scale (VAS), Kirkaldy-Willis criteria and the American Spinal Injury Association (ASIA) impairment scale. Radiographs were performed for measuring the angle of kyphosis and scoliosis. Complications related to surgery were recorded. RESULTS: All patients successfully resolved their infections, experienced one or more ASIA grades of improvement, and improved in their VAS pain scores at final follow-up. In both groups, patient-reported outcomes reached over 90% excellent or good results using Kirkaldy-Willis criteria. The loss of kyphotic angle correction was 2.6 degrees in the thoracic spinal tuberculosis group and 3.2 degrees in the thoracolumbar spinal tuberculosis group. No scoliosis was observed in either group. Fifty-eight (98.3%) cases achieved solid bony fusion. In the thoracolumbar spinal tuberculosis group, one patient experienced screw loosening, and another patient with nonunion and rod breakage underwent revision surgery. CONCLUSIONS: The technique of single-stage transpedicular debridement, posterior instrumentation and fusion is an effective method for the treatment of thoracic and thoracolumbar spinal tuberculosis in adults. Long-term postoperative clinical and radiological outcomes were satisfactory. PMID- 27387196 TI - Application of network analysis to identify interactive systems of eating disorder psychopathology. AB - BACKGROUND: Traditional approaches for the classification of eating disorders (EDs) attribute symptoms to an underlying, latent disease entity. The network approach is an alternative model in which mental disorders are represented as networks of interacting, self-reinforcing symptoms. This project was the first to use network analysis to identify interconnected systems of ED symptoms. METHOD: Adult participants (n = 143; 77.6% women) with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) ED were recruited from the community to take part in a larger ongoing longitudinal study. The Structured Clinical Interview for DSM Disorders (SCID-I) was used to establish diagnoses. An undirected network of ED symptoms was created using items from the Eating Pathology Symptoms Inventory (EPSI) and the R package qgraph. RESULTS: Body checking emerged as the strongest and most important single symptom in the entire network by having the shortest average distance to other symptoms in the network, and by being the most frequent symptom on the path between any two other symptoms. Feeling the need to exercise every day and two symptoms assessing dietary restraint/restricting emerged as 'key players', such that their removal from the network resulted in maximal fracturing of the network into smaller components. CONCLUSIONS: Although cognitive-behavioral therapy for EDs focuses on reducing body checking to promote recovery, our data indicate that amplified efforts to address body checking may produce stronger (and more enduring) effects. Finally, results of the 'key players analysis' suggested that targeting interventions at these key nodes might prevent or slow the cascade of symptoms through the 'network' of ED psychopathology. PMID- 27387197 TI - Clinical and radiological factors affecting progressive collapse of acute osteoporotic compression spinal fractures. AB - Osteoporotic compression spine fractures have a different clinical course and outcomes when compared to spinal fractures occurring in the younger population. Only a few studies have investigated the risk factors for progressive osteoporotic compression spine fractures. The purpose of this study was to investigate clinical and radiological factors related to progressive collapse following acute osteoporotic compression spine fractures. We retrospectively identified all patients treated for thoracolumbar fractures in our institution between January 2008 and July 2013. Included cases were examined by plain radiographs and CT scans. For each patient we classified the fracture according to the AOSpine Thoracolumbar Spine Injury Classification System. The difference between initial and final height loss and initial and final local kyphosis was documented as height loss difference and kyphotic angle difference. The presence of old fractures and intravertebral cleft were also documented. The study included 153 patients, comprising 102 women and 51 men. The mean patient age was 68.9years. The mean length of follow up was 15months. A statistically significant correlation was found between patient age, final height loss, height loss difference and kyphotic angle difference. Height loss difference and kyphotic angle difference were significantly correlated to type of fracture according to the AO classification system. The height loss difference was 18.1% in A1 type fractures, 27.1% in A2 type fractures, 24.2% in A3 type fractures and 25.7% in A4 type fractures. During a minimum 3-month follow up of conservative treatment for acute osteoporotic vertebral compression fractures, age and the AOSpine Thoracolumbar Spine Injury Classification System were predictive factors for progressive collapse. PMID- 27387198 TI - A Stiff and Healable Polymer Based on Dynamic-Covalent Boroxine Bonds. AB - A stiff and healable polymer is obtained by using the dynamic-covalent boroxine bond to crosslink PDMS chain into 3D networks. The as-prepared polymer is very strong and stiff, and can bear a load of more than 450 times its weight. When damaged, it can be completely healed upon heating after wetting. PMID- 27387199 TI - Required temporal resolution for accurate thoracic aortic pulse wave velocity measurements by phase-contrast magnetic resonance imaging and comparison with clinical standard applanation tonometry. AB - BACKGROUND: Pulse wave velocity (PWV) is a biomarker for arterial stiffness, clinically assessed by applanation tonometry (AT). Increased use of phase contrast cardiac magnetic resonance (CMR) imaging allows for PWV assessment with minor routine protocol additions. The aims were to investigate the acquired temporal resolution needed for accurate and precise measurements of CMR-PWV, and develop a tool for CMR-PWV measurements. METHODS: Computer phantoms were generated for PWV = 2-20 m/s based on human CMR-PWV data. The PWV measurements were performed in 13 healthy young subjects and 13 patients at risk for cardiovascular disease. The CMR-PWV was measured by through-plane phase-contrast CMR in the ascending aorta and at the diaphragm level. Centre-line aortic distance was determined between flow planes. The AT-PWV was assessed within 2 h after CMR. Three observers (CMR experience: 15, 4, and <1 year) determined CMR PWV. The developed tool was based on the flow-curve foot transit time for PWV quantification. RESULTS: Computer phantoms showed bias 0.27 +/- 0.32 m/s for a temporal resolution of at least 30 ms. Intraobserver variability for CMR-PWV were: 0 +/- 0.03 m/s (15 years), -0.04 +/- 0.33 m/s (4 years), and -0.02 +/- 0.30 m/s (<1 year). Interobserver variability for CMR-PWV was below 0.02 +/- 0.38 m/s. The AT-PWV overestimated CMR-PWV by 1.1 +/- 0.7 m/s in healthy young subjects and 1.6 +/- 2.7 m/s in patients. CONCLUSIONS: An acquired temporal resolution of at least 30 ms should be used to obtain accurate and precise thoracic aortic phase contrast CMR-PWV. A new freely available research tool was used to measure PWV in healthy young subjects and in patients, showing low intra- and interobserver variability also for less experienced CMR observers. PMID- 27387200 TI - A major outbreak of conjunctivitis caused by coxsackievirus A24, Reunion, January to April 2015. AB - From January to April 2015, Reunion experienced a major outbreak of acute haemorrhagic conjunctivitis (AHC) caused by coxsackievirus A24, which heavily impacted the healthcare system. According to the general practitioners' (GP) sentinel network, the number of medical consultations due to conjunctivitis during this period was estimated at ca 100,000. This report describes the characteristics of the outbreak, which were obtained through several different yet complementary surveillance systems on the island. These included the network of hospital emergency departments (OSCOUR network), the GPs' sentinel network, an Internet-based population cohort ('Koman i le') participating in a survey on distinct symptoms including 'red eyes' and the monitoring of eye drop sales. Overall the results of the different surveillance approaches were in good agreement regarding the outbreak dynamic. A peak of patients with conjunctivitis was detected in the first 15 days of March (week 10 and 11), coinciding with increased eye drop sales on the island. Strains recovered from outbreak cases belonged to genotype IV and were most closely related to strains identified in AHC outbreaks in China, Egypt and Japan since 2010. Continued surveillance of AHC in Reunion remains important not only locally, but also because frequent exchanges between the island and mainland France may lead to introduction of this virus in Europe. PMID- 27387202 TI - Can "realist" randomised controlled trials be genuinely realist? AB - In this paper, we respond to a paper by Jamal and colleagues published in Trials in October 2015 and take an opportunity to continue the much-needed debate about what applied scientific realism is. The paper by Jamal et al. is useful because it exposes the challenges of combining a realist evaluation approach (as developed by Pawson and Tilley) with the randomised controlled trial (RCT) design.We identified three fundamental differences that are related to paradigmatic differences in the treatment of causation between post-positivist and realist logic: (1) the construct of mechanism, (2) the relation between mediators and moderators on one hand and mechanisms and contexts on the other hand, and (3) the variable-oriented approach to analysis of causation versus the configurational approach.We show how Jamal et al. consider mechanisms as observable, external treatments and how their approach reduces complex causal processes to variables. We argue that their proposed RCT design cannot provide a truly realist understanding. Not only does the proposed realist RCT design not deal with the RCT's inherent inability to "unpack" complex interventions, it also does not enable the identification of the dynamic interplay among the intervention, actors, context, mechanisms and outcomes, which is at the core of realist research. As a result, the proposed realist RCT design is not, as we understand it, genuinely realist in nature. PMID- 27387201 TI - The impact of disease-related symptoms and palliative care concerns on health related quality of life in multiple myeloma: a multi-centre study. AB - BACKGROUND: Multiple myeloma, the second most common haematological cancer, remains incurable. Its incidence is rising due to population ageing. Despite the impact of the disease and its treatment, not much is known on who is most in need of supportive and palliative care. This study aimed to (a) assess symptom severity, palliative care concerns and health-related quality of life (HRQOL) in patients with multiple myeloma, and (b) to determine which factors are associated with a lower quality of life. We further wanted to know (c) whether general symptom level has a stronger influence on HRQOL than disease characteristics. METHODS: This multi-centre cross-sectional study sampled two cohorts of patients with multiple myeloma from 18 haematological cancer centres in the UK. The Myeloma Patient Outcome Scale (MyPOS) was used to measure symptoms and concerns. Measures of quality of life included the EORTC QLQ-C30, its myeloma module and the EuroQoL EQ-5D. Data were collected on socio-demographic, disease and treatment characteristics and phase of illness. Point prevalence of symptoms and concerns was determined. Multiple regression models quantified relationships between independent factors and the MyPOS, EORTC global quality of life item and EQ5D Index. RESULTS: Five-hundred-fifty-seven patients, on average 3.5 years (SD: 3.4) post-diagnosis, were recruited. 18.2 % had newly diagnosed disease, 47.9 % were in a treatment-free interval and 32.7 % had relapsed/progressive disease phase. Patients reported a mean of 7.2 symptoms (SD: 3.3) out of 15 potential symptoms. The most common symptoms were pain (72 %), fatigue (88 %) and breathlessness (61 %). Those with relapsed/progressive disease reported the highest mean number of symptoms and the highest overall palliative care concerns (F = 9.56, p < 0.001). Factors associated with high palliative care concerns were a general high symptom level, presence of pain, anxiety, low physical function, younger age, and being in the advanced stages of disease. CONCLUSION: Patients with multiple myeloma have a high symptom burden and low HRQOL, in the advanced and the earlier stages of disease. Identification of patients in need of supportive care should focus on assessing patient-reported outcomes such as symptoms and functioning regularly in clinical practice, complementary to traditional biomedical markers. PMID- 27387203 TI - Process evaluation of the Walk Well study: a cluster-randomised controlled trial of a community based walking programme for adults with intellectual disabilities. AB - BACKGROUND: Walking interventions can be effective in encouraging sedentary populations to become more active; however, limited research has explored the effectiveness of walking interventions for adults with intellectual disabilities. This process evaluation explored the delivery of a community based walking intervention for adults with intellectual disabilities. METHODS: Walk Well was a single-blind cluster randomised controlled trial of a 12-week physical activity consultation-led walking intervention. 102 participants were randomised to the Walk Well intervention or a waiting list control group. Participants in the intervention group received three physical activity consultations with a walking advisor at baseline, 6 & 12-weeks. They were encouraged to use a pedometer to set goals and monitor their daily step count. Primary outcome was change in daily step count at 12-weeks. Process evaluation measures included qualitative interviews with key stakeholders (n = 6) and quantifiable data collected as part of the intervention. Additional process data were extracted from a sub-set of qualitative interviews with participants and carers (n = 20). Data were analysed for process information related to context, recruitment and retention, reach, implementation, and fidelity. RESULTS: Walk Well was not effective in significantly increasing levels of physical activity. The process evaluation did, however, highlight several important areas for consideration in future studies, including: a successful recruitment and retention strategy reaching a representative sample of adults with intellectual disabilities in the community; feasible and (for most) enjoyable methods of engaging adults with intellectual disabilities in activities to support behaviour change; potential need for greater intervention duration and frequency of contact; advantages and disadvantages of using pedometers as a behaviour change tool; the need for strategies which engage carers in supporting participants; and the complex issue of 'freedom of choice' in relation to lifestyle behaviours and study participation. CONCLUSIONS: Walking interventions for adults with intellectual disabilities can be feasibly delivered in the community in relation to reach, recruitment, retention and intervention fidelity. More intensive intervention methods need to be explored as well as strategies to engage and motivate carers in their support of participants. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50494254 (3(rd) April 2012). PMID- 27387204 TI - Chemotherapy versus radiotherapy for FIGO stages IB1 and IIA1 cervical carcinoma patients with postoperative isolated deep stromal invasion: a retrospective study. AB - BACKGROUND: The adjuvant treatment for patients with isolated stromal invasion after radical hysterectomy and pelvic lymph node dissection (PLND) in FIGO stage IB1 and IIA1 cervical carcinoma has not been established. This study assessed the survival outcomes and recurrent patterns in this particular group of patients treated with chemotherapy or radiation-based adjuvant therapy. METHODS: The records 133 IB1 and IIA1 postoperative cervical carcinoma patients with histopathology-confirmed isolated deep stromal invasion (DSI) without any other unfavorable pathological finding between June 2010 and March 2013 were analyzed. Sixty-five patients received postoperative adjuvant four to six cycles of cisplatin-based chemotherapy (CT group) and Sixty-eight received postoperative received postoperative adjuvant radiotherapy (RT group). Treatment-related toxicities were evaluated and disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates and statistical significance was determined using the log-rank test. RESULTS: With a median follow-up of 33.7 months (range 10-62 months), RT group had a significantly improved in DFS rate (P = 0.044), but there was no significant difference in overall survival (P = 0.437). Upon further analysis, patients with outer 1/3 to full-thickness invasion in chemotherapy group exhibited significantly higher recurrence rates compared to the radiotherapy group. Leukocytopenia, nausea and vomiting were the most frequent short-term complications of chemotherapy, whereas colitis/proctitis and cystitis were more frequent in the radiotherapy group (P = 0.000 respectively). No significant differences were found regards to other acute toxicities, including hemoglobin, platelets and ALT/AST, colitis/proctitis, cystitis and dermatitis (P = 0.000 respectively). Fewer late severe side effects in the chemotherapy group were observed compared with the radiation group and significant differences were found at colitis/proctitis, cystitis and dermatitis (P = 0.000 respectively). CONCLUSION: Compared to chemotherapy alone, postoperative RT to FIGO stages IB1 and IIA1 cervical carcinoma patients with isolated DSI can reduce risk of recurrence and with acceptable morbidity. PMID- 27387205 TI - Assessing the Relationship Between Religious Involvement and Health Behaviors. AB - A growing body of research suggests that people who are more deeply involved in religion may be more likely to adopt beneficial health behaviors. However, religion is a complex phenomenon, and as a result, religion may affect health behaviors in a number of ways. The purpose of the current study was to see whether a sacred view of the body (i.e., belief that the body is the temple of God) is associated with better health behavior. It was proposed that the relationship between a sacred body view and health behavior will emerge only among study participants who have a stronger sense of religiously oriented control (i.e., stronger God-mediated control beliefs). Five positive health behaviors were evaluated: more frequent strenuous exercise, more frequent moderate exercise, more frequent consumption of fruits and vegetables, higher quality sleep, and the adoption of healthy lifestyles. Data from a recent nationwide sample reveal that a sacred body view is associated with each health behavior, but only among study participants who have a strong religiously oriented sense of control. PMID- 27387206 TI - Effects of new motorway infrastructure on active travel in the local population: a retrospective repeat cross-sectional study in Glasgow, Scotland. AB - BACKGROUND: Promoting active travel is an important part of increasing population physical activity, which has both physical and mental health benefits. A key benefit described by the then Scottish Government of the five-mile M74 motorway extension, which opened during June 2011 in the south of Glasgow, was that the forecast reduction in motor traffic on local streets would make these streets safer for walking and cycling, thus increasing active travel by the local population. The aim of the study was to evaluate the impact of new motorway infrastructure on the proportion of journey stages made actively (cycling or on foot) by individuals travelling in and out of the local area. METHODS: Data for the periods 2009-10 and 2012-13 were extracted from the Scottish Household Survey (SHS) travel diaries, which record each journey stage made during the previous day by a representative sample of the Scottish population aged 16 and over. Each individual journey stage was assigned to one of the following study areas surrounding existing and new transport infrastructure: (1) an area surrounding the new M74 motorway extension (n = 435 (2009-10), 543 (2012-13)), (2) a comparator area surrounding an existing motorway (n = 477 (2009-10), 560 (2012 13)), and (3) a control area containing no comparable motorway infrastructure (n = 541 (2009-10), 593 (2012-13)). Multivariable, multi-level regression analysis was performed to determine any between-area differences in change in active travel over time, which might indicate an intervention effect. Reference populations were defined using two alternative definitions, (1) Glasgow City and (2) Glasgow and surrounding local authorities. RESULTS: The results showed an increase in the proportion of journey stages using active travel in all study areas compared to both reference populations. However, there were no significant between-area differences to suggest an effect attributable the M74 motorway extension. CONCLUSIONS: There was no clear evidence that the M74 motorway extension either increased or decreased active travel in the local area. The anticipation by policy makers that reduced motorised traffic on local streets might increase journeys walked or cycled appears to have been unfounded. PMID- 27387207 TI - Influence of upper and temporal transconjunctival sclerocorneal incision on marginal reflex distance after cataract surgery. AB - BACKGROUND: Ptosis incidence following cataract surgery is reduced with a recently developed phacoemulsification technique using a small incision. However, it remains uncertain whether an upper transconjunctival sclerocorneal incision can cause minor blepharoptosis. In the present prospective study, patients underwent cataract surgery with either an upper or temporal 2.4-mm transconjunctival sclerocorneal incision. We measured the marginal reflex distance 1 (MRD1) preoperatively and postoperatively, and compared these measurements between the two different incision types. Further we explored the risk factors of the postoperative MRD1 reduction. METHODS: The study population included patients who underwent cataract surgery on both eyes at Aichi Medical University between October 2013 and September 2015. In each patient, one eye was operated using an upper 2.4-mm transconjunctival sclerocorneal incision, and the other with a temporal incision. We prespecified that an MRD1 difference of >=0.5 mm between the pre- and post-surgical measurements indicated postoperative ptosis, which was a strict criterion. MRD1 was measured using digital photography, and we calculated the difference between the preoperative and postoperative MRD1 values. This change in MRD1 was compared between the groups with different incision locations. The change in MRD1 was analyzed by using the multivariate regression model including incision position (temporal or upper), preoperative MRD1, and preoperative distance between medial and lateral canthi. RESULTS: We assessed data from a total of 34 patients. The mean change in MRD1 from pre-operation to post-operation measurements was -0.26 +/- 0.93 with the temporal incision and -0.24 +/- 0.86 with the upper incision. The mean difference in the change in MRD1 between the different two incision types was -0.02, with a 95 % CI of -0.24 to 0.20, establishing equivalence between these incision types. The multivariate regression analysis showed that the preoperative MRD1 was significantly associated with the reduction of MRD1 after surgery (p = 0.034). CONCLUSIONS: Cataract surgery using upper and temporal 2.4-mm transconjunctival sclerocorneal incisions are clinically equivalent with regards to change in MRD1, and neither incision type caused critical postoperative ptosis. The longer preoperative MRD1 was significantly associated with the reduction of MRD1 after surgery. TRIAL REGISTRATION: Current Controlled Trials UMIN000022310 . Retrospectively registered 14 May 2016. PMID- 27387208 TI - Effect of a new incision management system (PREVENA(r)) on wound healing after endophlebectomy of the common femoral vein: a case series. AB - BACKGROUND: New endovascular techniques facilitate treatment of complex deep vein obstructions in cases of post-thrombotic syndrome. In a relevant number of these patients, endophlebectomy including the implantation of an arteriovenous fistula between the common femoral artery and the femoral vein is indispensable in order to establish a good inflow. These procedures display a high risk of wound complications. Despite conservative efforts to prevent these postoperative complications, wound healing problems occur in more than 20 % of cases. The present case report is the first description of wound dressing using a PREVENA(r) incision management system in cases of endophlebectomy. CASE PRESENTATION: A single center's experience with the incision management system PREVENA(r), which was used after endophlebectomy and venous stenting in complex hybrid procedures in three white men aged 46 years, 53 years, and 61 years is the subject of this case report. Although the surgical procedures were performed under therapeutical anticoagulation and took a couple of hours, no wound complications occurred. CONCLUSIONS: These encouraging results underline a potential benefit of the incision management system PREVENA(r) in cases of complex venous recanalization including endophlebectomy of the femoral vein as well as the implantation of an arteriovenous fistula. PMID- 27387209 TI - What Is Next for NTDs in the Era of the Sustainable Development Goals? PMID- 27387210 TI - Practical aspects of drug interactions in the pharmacotherapy in otolaryngology, or the seven cardinal sins of pharmacological treatment in otolaryngological practice. AB - Drug interactions are a growing problem in the practice of otolaryngology. The use of drugs in patients treated with polypharmacy generates the risk of adverse drug interactions which requires specialized knowledge and active prevention. The most common interactions encountered by ENT physicians are identified on the basis of the analysis of medical order sheets and discussed in the article. PMID- 27387211 TI - The umami taste: from discovery to clinical use. AB - In the diversity of the flavor world only five basic tastes have been described. The newest one, umami, has been identified about one hundred years ago by Kikunae Ikeda but widely accepted just in the second half of the twentieth century by international scientific world. There are three umami substances: monosodium glutamate (MSG), inosine-5'-monophosphate (IMP), guanylo-5'-monophosphate (GMP). A real breakthrough in umami history concerned the finding about independent receptors for umami: T1R1 and T1R3 (taste receptors type 1 member 1 and member 3). The palatable, delicious taste of umami and its mechanism determined a lot of research studies on this highlight. Umami substances elicit salivary secretion, enhance appetite and increase food palatability. They are desirable to improve the quality of diet. Moreover, the association between umami substances and the suppression of obesity has been found. Studies suggest that umami is engaged in metabolism but also increases satiety and reduces the post-ingestive recovery of hunger. PMID- 27387212 TI - The incidence of laryngeal cancer in Europe with special regard to Poland in last 2 decades. AB - OBJECTIVE: Laryngeal cancer is a common respiratory cancer. We aimed to use data from European population-based cancer registries to present variations in the incidence and mortality of laryngeal cancer within Europe. METHODS: High-quality data from cancer registries were qualified for analysis. The pooled data were stratified by area, sex and age groups. RESULTS: The incidence and mortality rates of laryngeal cancer has been slightly decreasing for the last 10 years in Poland and other European countries. Laryngeal cancer is relatively rare in people under 40 years of age. Laryngeal cancer is significantly more common in men. CONCLUSIONS: Laryngeal cancer it is still a pathology which affects the quality of life of patients in the whole Europe. PMID- 27387213 TI - The influence of the body mass index (BMI) on selected parameters of the coagulation system in patients with disorders of the balance system taking oral contraceptives. AB - INTRODUCTION: The objective of the paper is to evaluate the influence of the body mass index (BMI) on selected parameters of the coagulation system in patients with disorders of the balance system taking oral contraceptives. MATERIAL AND METHODS: 105 young women participated in the study who were divided into 2 groups. Group I: 52 women disorders of the balance system taking hormonal contraceptives for at least 2 months, between the age of 20-49; Group II: 53 women with no disorders of the balance system taking hormonal contraceptives for at least 2 months, between the age of 18-40. Patients entering the study underwent full otoneurological examination, detailed laryngological assessment and the examination of selected parameters of the hemostasis system, including the evaluation of fibrinogen and D-dimer levels, APTT and PT, estradiol and progesterone concentrations in the blood serum and evaluation of the body mass index (BMI). RESULTS: Central vertigo was the most common type of vertigo in the study group (59,6% of cases). Other vertigo types in this group included compensated vertigo of mixed origin (36,6% of cases) and peripheral vertigo (only 3,8% of cases), which indicates that 40.4% of the cases suffer from damage to the labyrinth. The analysis of the concentration of estradiol in the blood serum revealed, after consideration of a menstrual cycle phase, that estradiol concentration exceeded normative values significantly more often in the study group than in the control group and that estradiol concentration was significantly less frequently below the norm in the study group; the difference was statistically significant (p=0,048). The body mass index (BMI) of women participating in the study significantly correlated with the concentration of D dimers only in the study group (p=0,35 vs p=0,012). CONCLUSIONS: Evaluating the body mass index before administering hormonal contraception can be useful to eliminate other risk factors for thromboembolism. In order to prevent potential thromboembolism episodes, administering hormonal contraception only after lowering the body mass index may also be worth considering. PMID- 27387214 TI - Assessment of inferior turbinate radiofrequency treatment: Monopolar versus bipolar. AB - OBJECTIVE: The aim of this study is to compare the early results of monopolar (MP) and bipolar (BP) radiofrequency (RF) used in inferior turbinate hypertrophy treatment concerning aspects of patient and surgeon comfort. STUDY DESIGN: Prospective randomized single-blind study. MATERIALS AND METHODS: The study included 71 patients with inferior turbinate hypertrophy resistant to medical treatment. BP RF was applied to 36 patients. MP RF was applied to 35 patients. Patients received no other treatment during their 6 months of follow-up examinations. They were evaluated by their symptoms (nasal obstruction severity, nasal obstruction frequency, postnasal drip, nasal crusting, hyposmia, patient satisfaction, and preoperative pain) with a visual analogue scale (VAS) done preoperatively on the 1st and 7th days and then in the 1st, 3rd, and 6th months postoperatively. RESULTS: No significant difference was observed comparing the symptoms of patients after BP and MP inferior turbinate RF in long-term follow up, whereas patients treated with MP RF showed early improvement in their symptoms on the 1st and 7th days postoperatively when compared to the BP group. The application time of MP RF was longer than that of the BP group. Pain during the operation was reported more frequently in the BP group. CONCLUSION: MP and BP RF treatment showed no difference in long-term efficacy. However, MP RF therapy showed early improvement in symptoms and less pain in patients than in the BP RF group. PMID- 27387215 TI - Biocompatible membrane of PDMS for the new chamber prosthesis stapes. AB - Stapes protheses are designed for patients with otosclerosis resulting immobilization or significant reduction of the stapes mobility. All currently used prostheses are called - piston prosthesis. However, its use to stimulate the cochlea is still imperfect. New chamber stapes prosthesis allows the perilymph excitation more effective than the piston prothesis. Moreover, the chamber prosthesis eliminates the common causes of piston-stapedotomy failures. The most important element of the new prosthesis is a flexible membrane. The membrane stiffness should be close to the stiffness of normal annular ligament. This work presents the process of selection of the membrane's thickness and its manufacturing technology. Method A 3D model of the chamber stapes prosthesis was build using Autodesk Inventor 2015. The model was imported to Abacus 6.13 computing environment. During numerical simulations, displacements corresponding to applied loads were calculated and the membrane thickness was adjusted so that its stiffness was the same as the ligament stiffness (~ 120 N/m). The compliance ratios calculated from the load-displacement curves for the membrane and the annular ligament were verified using linear regression analysis. After determining the thickness, the manufacturing technology of the membrane was developed. Results The best similarity between the membrane's and annular ligament's stiffness was achieved for PDMS membrane with the 0,15- mm thickness (similarity ratio R2=0,997752). In this work, the technological parameters of spin-coating process for membrane manufacture are also presented. Summary The proper functioning of the chamber stapes prosthesis requires the PDMS membrane with a thickness of 0,15 mm. The 0,15-mm membrane has the tiffness close to the stiffness of the normal annular ligament. Therefore, the chamber stapes prosthesis provides the perilymph stimulation at the level comparable to the healthy ear. New prosthesis is currently under pre-clinical investigation to optimize the shape of the inner chamber's surface. PMID- 27387216 TI - Analysis of difficulties occurring during the early auditory screening in children. AB - INTRODUCTION: It is assumed that the critical period for diagnosis of hearing disorders is the baby's first three months of life and that appropriate course and implementation of treatment and/or rehabilitation should begin before a child is six months old. However various kinds of problems may occur during auditory screening of a child may exceed this interval. This problem is particularly pronounced among children with development and health problems and leads to unreliable and varied results. AIM: The aim of this study was an analysis of prevalence of difficulties occurring during the first year of auditory screening among groups of children with congenital hearing impairment. MATERIAL AND METHODS: Patients were examined in The Universal Newborn Hearing Screening Program in the years 2012 - 2013 in Level III NICUs in Krakow. Results from 250 cases were analyzed retrospectively. Medical exam results of patients with high risk of hearing loss were also included in our analysis. The groups of children included in our study were: children with Down Syndrome, children with nervous system disorders , children with cleft palate or both cleft palate and lip and children with congenital CMV. RESULTS: In the group of children with cleft palate or both cleft palate and lip the most frequent cause of not conducting objective audiometric tests was bad health condition of a child which precluded his arrival for administering the tests. The most common cause of difficulties in performing hearing tests was the emotional state of children from groups with Down Syndrome. In the group of children with congenital CMV the most common cause of difficulties was a lack of availability of their parents. CONCLUSIONS: 1. We encountered the greatest diagnostic difficulties during the child's first year of life in chosen high-risk groups of children with congenital hearing loss in children with cleft palate or both cleft palate and lip. 2. The highest prevalence of not finished tests was in III and IV interval for all chosen high risk groups with congenital hearing loss. PMID- 27387217 TI - Putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression. AB - The morphological development of fungi is a complex process and is often coupled with secondary metabolite production. In this study, we assessed the function of putative methyltransferase LaeA and transcription factor CreA in controlling asexual development and secondary metabolic gene cluster expression in Penicillium oxalicum. The deletion of laeA (DeltalaeA) impaired the conidiation in P. oxalicum, with a downregulated expression of brlA. Overexpression of P. oxalicum brlA in DeltalaeA could upregulate brlA and abaA remarkably, but could not rescue the conidiation defect; therefore, brlA and abaA expression were necessary but not sufficient for conidiation. Deletion of creA in DeltalaeA background (DeltalaeADeltacreA) blocked conidiation with a white fluffy phenotype. Nutrient-rich medium could not rescue developmental defects in DeltalaeADeltacreA mutant but could rescue defects in DeltalaeA. Expression of 10 genes, namely, albA/wA, abrB/yA, arpA, aygA, arpA-like, arpB, arpB-like, rodA, rodA-like, and rodB, for pigmentation and spore wall protein genes was silenced in DeltalaeADeltacreA, whereas only six of them were downregulated in DeltalaeA. Among the 28 secondary metabolism gene clusters in P. oxalicum, four secondary metabolism gene clusters were silenced in DeltalaeA and two were also silenced in DeltabrlA mutant. A total of 10 physically linked and coregulated genes were distributed over five chromosomes in DeltalaeA. Six of these genes were located in subtelomeric regions, thus demonstrating a positional bias for LaeA-regulated clusters toward subtelomeric regions. All of silenced clusters located in subtelomeric regions were derepressed in DeltalaeADeltacreA, hence showing that lack of CreA could remediate the repression of gene clusters in DeltalaeA background. Results show that both putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression. PMID- 27387218 TI - Septins are involved in nuclear division, morphogenesis and pathogenicity in Fusarium graminearum. AB - Septins are GTP-binding proteins that regulate cell polarity, cytokinesis and cell morphogenesis. Fusarium head blight (FHB), caused by Fusarium graminearum, is one of the most devastating diseases worldwide. In this study, we have functionally characterized the core septins, Cdc3, Cdc10, Cdc11 and Cdc12 in F. graminearum. The loss of FgCdc3, FgCdc11, FgCdc12, but not FgCdc10, mutants showed significant reduction in growth, conidiation and virulence. Microscopic analyses revealed that all of them were involved in septum formation and nuclear division. Moreover, disruption of septin genes resulted in morphological defects in ascospores and conidia. Interestingly, conidia produced by DeltaFgcdc3, DeltaFgcdc11 and DeltaFgcdc12 mutants exhibited deformation with interconnecting conidia in contrast to their parent wild-type strain PH-1 and the DeltaFgcdc10 mutant that produced normal conidia. Using yeast two-hybrid assays, we determined the interactions among FgCdc3, FgCdc10, FgCdc11 and FgCdc12. Taken together, our results indicate that septins play important roles in the nuclear division, morphogenesis and pathogenicity in F. graminearum. PMID- 27387219 TI - Association between atrial function assessed by 2D-speckle tracking echocardiography and albuminuria in patients with type 2 diabetes and coronary artery disease. AB - PURPOSE: We compared left atrial function as assessed by two-dimensional speckle tracking echocardiography (2DSTE) between patients with type 2 diabetes and coronary artery disease (CAD) with or without albuminuria, nondiabetic patients without CAD, and CAD patients without type 2 diabetes. METHODS: This cross sectional study was performed on 112 consecutive patients with CAD (28 nonalbuminuric patients without diabetes, 40 nonalbuminuric patients with type 2 diabetes, and 44 albuminuric patients with type 2 diabetes) and 30 consecutive patients with no CAD, no diabetes, and no albuminuria. Spot urine analysis was performed to measure the urine level of creatinine and albumin. Atrial mechanical variables were measured by 2DSTE. RESULTS: Although systolic strain and the absolute value of early diastolic strain rate were lower in the CAD groups than in the non-CAD group, there were no significant differences between the CAD groups. Early diastolic strain was lower in the diabetic patients with CAD than in the nondiabetic non-CAD group. There were, however, no significant differences between the CAD groups. CONCLUSIONS: In our CAD patients, there was no significant association between the presence of type 2 diabetes mellitus and albuminuria and left atrial function, but the reservoir and conduit function of the left atrium were lower in the CAD patients. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:561-570, 2016. PMID- 27387221 TI - [Results, safety and patient satisfaction at 6 months of vaginal anterior wall prolapse surgery by transvaginal repair with mesh use]. AB - OBJECTIVE: To assess at 6 months the efficiency, the safety and the satisfaction of a lightweight polypropylene mesh used for the transvaginal repair of cystocele by bilateral anterior sacrospinous ligament fixation (NUVIATM SI). MATERIEL AND METHODS: A prospective cohort study was performed from January 2014 to June 2015. Preoperative assessment included an evaluation using the Pelvic Organ Prolapse Quantification system (POP-Q) and 3 questionnaires about symptoms, quality of life and quality of sex life (PFDI-20, PFIQ7, PISQ-12). Results were evaluated by a composite criteria: Ba<=0, absence of bulge sensation and absence of reoperation for cystocele recurrence. Secondary objectives were to assess the complications rates and patient's satisfaction. RESULTS: In 10 months, 16 patients, with a mean age of 61.9+/-8.8years, were included and evaluated by an independent observator at 6months. Four patients were sexually active before surgery and 5 at 6 months. Results were optimal in 93.75% cases (15/16) with one intraoperative injury (bladder injury) and one postoperative complication (increase of preoperative dyspareunia). Satisfaction rate was 93.75% (15/16) and questionnaires PFDI-20 and PFIQ-7 were statistically improved (P<0.0001 and P=0.0013). Three patients had a reintervention but not about anterior wall prolapse (section of a suburethral sling for urinary retention, suburethral sling exposure and cure of stress urinary incontinence). CONCLUSION: At short term, transvaginal mesh repair by anterior sacrospinous ligament fixation with NUVIATM presents 93.75% optimal result with one case of increased dyspareunia and 3 reoperations which don't concern anterior wall (urinary outcomes). LEVEL OF EVIDENCE: 4. PMID- 27387220 TI - A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus. AB - In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128 131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID- 27387222 TI - [Spontaneous rupture of ileal neobladder 8 years after surgery: A case report]. PMID- 27387223 TI - Adaptation of the MacArthur-Bates Communicative Development Inventories for Spanish Children With Down Syndrome: Validity and Reliability Data for Vocabulary. AB - PURPOSE: The MacArthur-Bates Communicative Development Inventories are widely used to study early language and communicative development. We recently developed a Spanish version for children with Down syndrome (the CDI-Down) adapted to their particular profile of linguistic and communicative development. The principal aims of this study are to assess the concurrent validity and test-retest reliability of the vocabulary section of this adaptation. METHOD: Validation for productive vocabulary (Study 1) was achieved by correlating CDI-Down scores on expressive vocabulary and measures on the basis of spontaneous speech samples (n = 29). Validation for receptive vocabulary (Study 2) was achieved by correlating CDI-Down scores on receptive vocabulary and measures derived from language items of the Brunet-Lezine Scale (Josse, 1997; n = 70). Reliability (Study 3) was measured with a subset of parents who completed the same inventory 4 months after the original sampling (n = 26). RESULTS: CDI-Down expressive and receptive vocabulary scores showed a significant positive relationship with their comparison measures, thereby demonstrating convergent validity. A significant positive relationship was also found between test-retest measures for productive and receptive vocabularies, thus supporting the reliability of the adaptation. CONCLUSION: The results demonstrate that the CDI-Down is a valid and reliable tool that could be useful for parents, teachers, clinicians, and researchers. PMID- 27387224 TI - Prevalence and emergence of carbapenemases-producing Gram-negative bacteria in Mediterranean basin. AB - The emergence and the global spread of carbapenemases concern to health services worldwide. Their celestial rise among Gram-negative bacilli has challenged both the scientific and pharmaceutical sectors. Indeed, infections caused by these bacteria have limited treatment options and have been associated with high mortality and morbidity rates. Carbapenemase producers are mainly identified among Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii and still mostly in hospital settings and rarely in the community. They are closely related to KPC, VIM, IMP, NDM, and OXA-48 types. The encoding genes are mostly plasmid located and associated with various mobile genetic elements. The Mediterranean area is of interest due to a great diversity and population mixing. The prevalence of carbapenemases is particularly high and variant among countries, partially depending on the population exchange relationship between the regions and the possible reservoirs of each carbapenemase. This review described the epidemiology of carbapenemases in this region of the world highlighting the worrisome situation and the need to screen and detect these enzymes to prevent and control their dissemination especially as it is clear that very few novel antibiotics will be introduced in the next few years, making the dissemination of carbapenem-resistant Gram-negative bacteria of crucial importance worldwide. PMID- 27387225 TI - Clinical mastitis in breastfeeding women: study of 56 cases. PMID- 27387226 TI - Efficacy and safety of ketamine in bipolar depression: A systematic review. AB - The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects. PMID- 27387227 TI - Nano-TiO2 penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa models. AB - BACKGROUND: Oral cavity is a doorway for a variety of products containing titanium dioxide (TiO2 ) nanoparticles (NPs) (nano-TiO2 ) such as food additives, oral healthcare products and dental materials. Their potential to penetrate and affect normal human oral mucosa is not yet determined. OBJECTIVES: To evaluate the ability of nano-TiO2 to penetrate the in vitro reconstructed normal human buccal mucosa (RNHBM). METHODS: RNHBM was generated from primary normal human oral keratinocytes and fibroblasts isolated from buccal oral mucosa of healthy patients (n = 6). The reconstructed tissues were exposed after 10 days to clinically relevant concentrations of spherical or spindle rutile nano-TiO2 in suspension for short (20 min) and longer time (24 h). Ultrahigh-resolution imaging (URI) microscopy (CytoVivaTM , Auburn, AL, USA) was used to assess the depth of penetration into reconstructed tissues. RESULTS: Ultrahigh-resolution imaging microscopy demonstrated the presence of nano-TiO2 mostly in the epithelium of RNHBM at both 20 min and 24-h exposure, and this was shape and doze dependent at 24 h of exposure. The depth of penetration diminished in time at higher concentrations. The exposed epithelium showed increased desquamation but preserved thickness. CONCLUSION: Nano-TiO2 is able to penetrate RNHBM and to activate its barrier function in a doze- and time-dependent manner. PMID- 27387229 TI - SAMHD1, the Aicardi-Goutieres syndrome gene and retroviral restriction factor, is a phosphorolytic ribonuclease rather than a hydrolytic ribonuclease. AB - SAMHD1 plays diverse roles in innate immunity, autoimmune diseases and HIV restriction, but the mechanisms involved are still unclear. SAMHD1 has been reported to have both dNTPase and RNase activities. However, whether SAMHD1 possesses RNase activity remains highly controversial. Here, we found that, unlike conventional hydrolytic exoribonucleases, SAMHD1 requires inorganic phosphate to degrade RNA substrates and produces nucleotide diphosphates rather than nucleoside monophosphates, which indicated that SAMHD1 is a phosphorolytic but not hydrolytic 3'-5' exoribonuclease. Furthermore, SAMHD1 preferentially cleaved single-stranded RNAs comprising A20 or U20, whereas neither C20 nor G20 was susceptible to SAMHD1-mediated degradation. Our findings will facilitate more advanced studies into the role of the SAMHD1 RNase function in the cellular pathogenesis implicated in nucleic acid-triggered inflammatory responses and the anti-retroviral function of SAMHD1. PMID- 27387228 TI - A potato model intercomparison across varying climates and productivity levels. AB - A potato crop multimodel assessment was conducted to quantify variation among models and evaluate responses to climate change. Nine modeling groups simulated agronomic and climatic responses at low-input (Chinoli, Bolivia and Gisozi, Burundi)- and high-input (Jyndevad, Denmark and Washington, United States) management sites. Two calibration stages were explored, partial (P1), where experimental dry matter data were not provided, and full (P2). The median model ensemble response outperformed any single model in terms of replicating observed yield across all locations. Uncertainty in simulated yield decreased from 38% to 20% between P1 and P2. Model uncertainty increased with interannual variability, and predictions for all agronomic variables were significantly different from one model to another (P < 0.001). Uncertainty averaged 15% higher for low- vs. high input sites, with larger differences observed for evapotranspiration (ET), nitrogen uptake, and water use efficiency as compared to dry matter. A minimum of five partial, or three full, calibrated models was required for an ensemble approach to keep variability below that of common field variation. Model variation was not influenced by change in carbon dioxide (C), but increased as much as 41% and 23% for yield and ET, respectively, as temperature (T) or rainfall (W) moved away from historical levels. Increases in T accounted for the highest amount of uncertainty, suggesting that methods and parameters for T sensitivity represent a considerable unknown among models. Using median model ensemble values, yield increased on average 6% per 100-ppm C, declined 4.6% per degrees C, and declined 2% for every 10% decrease in rainfall (for nonirrigated sites). Differences in predictions due to model representation of light utilization were significant (P < 0.01). These are the first reported results quantifying uncertainty for tuber/root crops and suggest modeling assessments of climate change impact on potato may be improved using an ensemble approach. PMID- 27387230 TI - The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo. AB - In the present study, we tested the anti-pancreatic cancer activity by AT406, a small-molecule antagonist of IAP (inhibitor of apoptosis proteins). In established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells, treatment of AT406 significantly inhibited cell survival and proliferation. Yet, same AT406 treatment was non-cytotoxic to pancreatic epithelial HPDE6c7 cells. AT406 increased caspase-3/-9 activity and provoked apoptosis in the pancreatic cancer cells. Reversely, AT406' cytotoxicity in these cells was largely attenuated with pre-treatment of caspase inhibitors. AT406 treatment caused degradation of IAP family proteins (cIAP1 and XIAP) and release of cytochrome C, leaving Bcl-2 unaffected in pancreatic cancer cells. Bcl-2 inhibition (by ABT-737) or shRNA knockdown dramatically sensitized Panc-1 cells to AT406. In vivo, oral administration of AT406 at well-tolerated doses downregulated IAPs (cIAP1/XIAP) and inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) nude mice. Together, our preclinical results suggest that AT406 could be further evaluated as a promising anti pancreatic cancer agent. PMID- 27387231 TI - Licoflavonol is an inhibitor of the type three secretion system of Salmonella enterica serovar Typhimurium. AB - As an important food-borne human pathogen, Salmonella enterica serovar Typhimurium depends on its type III secretion system (T3SS) as a major virulence factor to cause disease all over the world. The T3SS secretes effector proteins to facilitate invasion into host cells. In this study, twenty prenylated flavonoids (1-20) were screened for their anti-T3SS activity, revealing that several analogs exhibited strong inhibitory effects on the secretion of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins without affecting the growth of bacteria and the secretion of the flagellar protein FliC. Among the flavonoids 1-20, licoflavonol (20) exhibited a strong inhibitory effect on the secretion of the SPI-1 effector proteins via regulating the transcription of the SicA/InvF genes, and the transportation of the effector protein SipC. In summary, licoflavonol, a novel natural inhibitor of Salmonella T3SS, could be a promising candidate for novel type of anti-virulence drugs. PMID- 27387232 TI - Wnt/beta-catenin signaling promotes regeneration after adult zebrafish spinal cord injury. AB - Unlike mammals, zebrafish can regenerate their injured spinal cord and regain control of caudal tissues. It was recently shown that Wnt/beta-catenin signaling is necessary for spinal cord regeneration in the larval zebrafish. However, the molecular mechanisms of regeneration may or may not be conserved between larval and adult zebrafish. To test this, we assessed the role of Wnt/beta-catenin signaling after spinal cord injury in the adult zebrafish. We show that Wnt/beta catenin signaling is increased after spinal cord injury in the adult zebrafish. Moreover, overexpression of Dkk1b inhibited Wnt/beta-catenin signaling in the regenerating spinal cord of adult zebrafish. Dkk1b overexpression also inhibited locomotor recovery, axon regeneration, and glial bridge formation in the injured spinal cord. Thus, our data illustrate a conserved role for Wnt/beta-catenin signaling in adult and larval zebrafish spinal cord regeneration. PMID- 27387233 TI - Extracellular S100A4 affects endothelial cell integrity and stimulates transmigration of A375 melanoma cells. AB - High extracellular S100A4 level proves a specific characteristic of some cancer cases, including malignant melanoma. Concerning the latter, extracellular S100A4 in an autocrine manner was shown to promote prometastatic activation of A375 cells by interaction with the receptor for advanced glycation endproducts (RAGE). We hypothesized that interaction of extracellular S100A4 with RAGE in a paracrine manner will affect endothelial cell (EC) integrity thus further promoting melanoma metastasis. We investigated the influence of recombinant and cell (A375) derived S100A4 on junction protein expression and EC (hCMEC/D3) integrity by measuring transendothelial electrical resistance (TEER). Decrease of TEER and diminished expression of both occludin and VE-cadherin revealed the loss of EC integrity. Transmigration of transgenic A375 cells (A375-hS100A4/A375-hRAGE) through the EC monolayer was significantly higher compared to wild-type A375 cells, and was substantially decreased by sRAGE. A pilot study in mice, intracardially injected with A375-hS100A4 or A375-hRAGE cells, showed lower survival rates and a higher incidence of metastases compared to wild-type A375 cells. Tumor development was mostly located in the brain, bones, and ovaries. These findings provide further evidence on extracellular S100A4 as paracrine mediator of prometastatic endothelial dysfunction involving its interaction with RAGE. PMID- 27387234 TI - Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity. AB - The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. PMID- 27387235 TI - Kir2.1 regulates rat smooth muscle cell proliferation, migration, and post-injury carotid neointimal formation. AB - Phenotype switching of vascular smooth muscle cells (VSMC) from the contractile type to the synthetic type is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Inward rectifier K(+) channel 2.1 (Kir2.1) has been identified in VSMC. However, whether it plays a functional role in regulating cellular transformation remains obscure. In this study, we evaluated the role of Kir2.1 on VSMC proliferation, migration, phenotype switching, and post-injury carotid neointimal formation. Kir2.1 knockdown significantly suppressed platelet-derived growth factor BB-stimulated rat vascular smooth muscle cells (rat-VSMC) proliferation and migration. Deficiency in Kir2.1 contributed to the restoration of smooth muscle alpha-actin, smooth muscle 22alpha, and calponin and to a reduction in osteopontin expression in rat VSMC. Moreover, the in vivo study showed that rat-VSMC switched to proliferative phenotypes and that knockdown of Kir2.1 significantly inhibited neointimal formation after rat carotid injury. Kir2.1 may be a potential therapeutic target in the treatment of cardiovascular diseases, such as atherosclerosis and restenosis following percutaneous coronary intervention. PMID- 27387236 TI - DnaT is a PriC-binding protein. AB - DnaT and PriC are replication restart primosomal proteins required for re initiating chromosomal DNA replication. DnaT is a component of the PriA-dependent primosome, while PriC belongs to the PriC-dependent primosome. Whether DnaT can interact with PriC is still unknown. In this study, we define a direct interaction between PriC, a key initiator protein in PriC-mediated DNA replication restart, and DnaT, a DnaB/C complex loader protein, from Klebsiella pneumoniae. In fluorescence titrations, PriC bound to single-stranded DNA with a binding-site size of approximately 9 nt. Gold nanoparticle assay showed that the solution of DnaT-PriC changed from red to purple, which indicated the protein protein interactions due to gold nanoparticle aggregate. In addition, this DnaT PriC complex could be co-purified by the heparin HP column. Surface plasmon resonance analysis showed that the Kd value of DnaT bound to PriC was 2.9 * 10( 8) M. These results constitute a pioneering study of the DnaT-PriC interaction and present a putative link between the two independent replication restart pathways, namely, PriA- and PriC-dependent primosome assemblies. Further research can directly focus on determining how DnaT binds to the PriC-SSB-DNA tricomplex and regulates the PriC-dependent replication restart. PMID- 27387237 TI - Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition. AB - The opportunistic human pathogen Serratia marcescens AS-1 produces the N hexanoylhomoserine lactone (C6HSL) receptor SpnR, a homologue of LuxR from Vibrio fischeri, which activates pig clusters to produce the antibacterial prodigiosin. In this study, we attempted to artificially regulate quorum sensing (QS) by changing the role of SpnR in N-acylhomoserine lactone (AHL)-mediated QS. SpnR was obtained as a fusion protein tagged with maltose-binding protein (MBP) from overexpression in Escherichia coli, and its specific affinity to C6HSL was demonstrated by quartz crystal microbalance analysis and AHL-bioassay with Chromobacterium violaceum CV026. Prodigiosin production was effectively inhibited by externally added MBP-SpnR in both wild-type AS-1 and the AHL synthase defective mutant AS-1(DeltaspnI). For the mutant, the induced amount of prodigiosin was drastically reduced to approximately 4% with the addition of 18 MUM MBP-SpnR to the liquid medium, indicating 81% trapping of C6HSL. A system for inhibiting QS can be constructed by adding exogenous AHL receptor to the culture broth to keep the concentration of free AHL low, whereas intracellular SpnR naturally functions as the activator in response to QS. PMID- 27387238 TI - The KYxxL motif in Rad17 protein is essential for the interaction with the 9-1-1 complex. AB - ATR-dependent DNA damage checkpoint is the major DNA damage checkpoint against UV irradiation and DNA replication stress. The Rad17-RFC and Rad9-Rad1-Hus1 (9-1-1) complexes interact with each other to contribute to ATR signaling, however, the precise regulatory mechanism of the interaction has not been established. Here, we identified a conserved sequence motif, KYxxL, in the AAA+ domain of Rad17 protein, and demonstrated that this motif is essential for the interaction with the 9-1-1 complex. We also show that UV-induced Rad17 phosphorylation is increased in the Rad17 KYxxL mutants. These data indicate that the interaction with the 9-1-1 complex is not required for Rad17 protein to be an efficient substrate for the UV-induced phosphorylation. Our data also raise the possibility that the 9-1-1 complex plays a negative regulatory role in the Rad17 phosphorylation. We also show that the nucleotide-binding activity of Rad17 is required for its nuclear localization. PMID- 27387239 TI - Silver adducts of four-branched histidine rich peptides exhibit synergistic antifungal activity. AB - Previously, a four branched histidine-lysine rich peptide, H3K4b, was shown to demonstrate selective antifungal activity with minimal antibacterial activity. Due to the potential breakdown from proteases, H3K4b was further evaluated in the current study by varying the D- and l-amino acid content in its branches. Whereas analogues of H3K4b that selectively replaced l-amino acids (H3k4b, h3K4b) had improved antifungal activity, the all d-amino acid analogue, h3k4b, had reduced activity, suggesting that partial breakdown of the peptide may be necessary. Moreover, because histidines form coordination bonds with the silver ion, we examined whether silver adducts can be formed with these branched histidine lysine peptides, which may improve antifungal activity. For Candida albicans, the silver adduct of h3K4b or H3k4b reduced the MIC compared to peptide and silver ions alone by 4- and 5-fold, respectively. For Aspergillus fumigatus, the silver adducts showed even greater enhancement of activity. Although the silver adducts of H3k4b or h3K4b showed synergistic activity, the silver adduct with the all l amino acid H3K4b surprisingly showed the greatest synergistic and growth inhibition of A. fumigatus: the silver adduct of H3K4b reduced the MIC compared to the peptide and silver ions alone by 30- and 26-fold, respectively. Consistent with these antifungal efficacy results, marked increases in free oxygen radicals were produced with the H3K4b and silver combination. These studies suggest that there is a balance between stability and breakdown for optimal antifungal activity of the peptide alone and for the peptide-silver adduct. PMID- 27387240 TI - Ten-year estimated risk of bone fracture in women with differentiated thyroid cancer under TSH-suppressive levothyroxine therapy. AB - INTRODUCTION: After thyroidectomy and radioiodine therapy, patients with differentiated thyroid cancer (DTC) are indefinitely treated with levothyroxine (L-T4). Osteoporosis is a debated consequence of hypothyroxinaemia. The aim of this study was to evaluate bone mineral density (BMD) and fracture risk assessed by FRAX in a cohort of DTC women. MATERIAL AND METHODS: Seventy-four women with DTC (aged 56.5 +/- 9.9 years) treated at the mean age of 51.9 +/- 12.0 years were studied. Baseline BMD and FRAX were evaluated after 3.0 years (median). BMD and FRAX were further evaluated 5.5 years (median) after the baseline evaluation. A cohort of 120 euthyroid women, matched for age, BMI, and menopausal status, were evaluated as controls. RESULTS: L-T4 dosages were 813.6 +/- 208.8 MUg/week and 782.1 +/- 184.4 MUg/week at the baseline and second evaluation, respectively. The risks of major osteoporotic fracture (MOF) and hip fracture (HF) were similar in DTC patients and in controls. In DTC women, significant changes in FRAX were found, with a higher increase in the probability of HF than of MOF. A similar change was found in controls. A significant inverse correlation (P < 0.001) between L-T4 dosage and HF/MOF probability on both first and second evaluations was found. A significant inverse correlation (P = 0.05) was found between fT4, TSH and duration of therapy and HF/MOF probability only on the second evaluation. CONCLUSIONS: FRAX increase is a multi-factorial, age-related phenomenon. The absence of correlations between L-T4 dosage, length of therapy or fT4 levels and FRAX does not enable us to attribute an increased fracture risk to DTC women with well-controlled disease on therapy. (Endokrynol Pol 2016; 67 (4): 350-358). PMID- 27387241 TI - Determination of advanced glycation end-products and antibodies against them (anti-CML and anti-CEL) in the serum of Graves' orbitopathy patients before and after methylprednisolone treatment. AB - INTRODUCTION: The glycation process is a non-enzymatic modification of proteins occurring due to the reactions of reductive carbohydrates. The glycated residues lose their biological functions, and their removal process is ineffective. They accumulate, and as a result they cause an immunological response. The aim of this study was a determination of the concentrations of advanced glycation end products and antibodies against carboxymethyl lysine (anti-CML) and carboxyethyl lysine (anti-CEL) in the sera of Graves' orbitopathy patients. MATERIAL AND METHODS: The study group were patients from the Division of Endocrinology of the Medical University of Silesia (n = 25) suffering from Graves' orbitopathy. The concentration of AGE-peptides using flow spectrofluorimetry method, and anti-CML and anti-CEL IgG antibodies using immunoenzymatic technique (ELISA), were measured in patients sera before and after methylprednisolone treatment. RESULTS: In sera of the study group the concentrations of AGE-peptides and anti-CML were significantly lower before and after treatment in comparison to the control group (p < 0.05). Mean values of anti-CEL concentrations were comparable (at both phases of treatment) with the value observed in the control group. After treatment the concentrations of AGE-peptides and anti-CEL significantly decreased (p < 0.05); however, the concentration of anti-CML was also lower but the observed change was not significant (p > 0.05). CONCLUSIONS: In the course of Graves' orbitopathy the glycation process is disturbed. The treatment modifies significantly the process by lowering the concentration of advanced glycation end products and suppressing the immune response to them. (Endokrynol Pol 2016; 67 (4): 383-389). PMID- 27387242 TI - Soluble alpha-Klotho - a new marker of acromegaly? AB - INTRODUCTION: Klotho is a transmembrane protein that attenuates insulin/insulin like growth factor-1 (IGF-1) signalling and appears to be involved in ageing. Recent data suggest that soluble a-Klotho (sKlotho) is also elevated in acromegaly. The aim of this study was to assess serum levels of sKlotho in patients in relation to the activity of the disease and to compare with the control group. MATERIAL AND METHODS: We studied 55 patients with acromegaly and 29 healthy controls (CG). Patients were divided into three subgroups according to minimal GH (growth hormone) concentration during the oral glucose tolerance test (OGTT) and the IGF-1 concentration: a surgically cured acromegalic group (SCA), well-controlled acromegalic group (WCA), and active acromegaly group (AA). In all subjects, blood samples were taken to assess the concentration of sKlotho, GH, IGF-1, and biochemical markers. RESULTS: Soluble a-Klotho was highest in the AA group and lowest in the SCA group. The differences in sKlotho levels were statistically significant when the AA group was compared to the SCA, WCA, and CG groups (p = 0.000, p = 0.002, p = 0.001, respectively). There were no significant differences in sKlotho levels among the SCA, WCA, and CG groups. sKlotho positively correlated with GH levels in the WCA and WCA + SCA groups (r = 0.666, p = 0.009; r = 0.366, p = 0.047, respectively) and with the IGF-1 level in the AA group (r = 0.589, p = 0.021). CONCLUSIONS: sKlotho is increased in active acromegaly and normalises after successful treatment. It could be a new biomarker of acromegaly activity. (Endokrynol Pol 2016; 67 (4): 390-396). PMID- 27387243 TI - Iodine supplementation during pregnancy of hypothyroid women treated with L thyroxine neither influences neonatal TSH nor prevents decrease in maternal free thyroid hormone concentrations in second and third trimesters. AB - INTRODUCTION: Pregnant women require about 250 MUg of iodine daily. Hypothyroid women treated with L-thyroxine do not utilise iodine, and metabolism of L thyroxine tablets is an additional source of iodine for their foetuses. The aim of the study was to evaluate the influence of iodine supplementation in hypothyroid pregnant women treated with L-thyroxine on neonate TSH concentration and maternal thyroid parameters. MATERIAL AND METHODS: Ninety-two pregnant women with primary hypothyroidism on adequate thyroid hormone replacement were voluntarily divided into two groups: "thyroxine" (n = 38) treated with L thyroxine only, and "thyroxine + iodine" (n = 54) treated additionally with 150 MUg/day of iodine since 10th gestational week. Primary outcomes were the maternal thyroid function tests (TSH, fT4, fT3) and neonatal TSH concentrations at the 3 4th day of life. Urinary iodine concentration was measured at first and third trimester to compare iodine status in both groups. RESULTS: Iodine supplementation significantly increased median urinary ioduria in the third trimester (from 95.15 MUg/L to 151.50 MUg/L), but did not prevent the decrease of maternal fT4 and fT3 concentrations in the second and third trimester. Median neonate TSH concentration in both groups was within normal range, but was 33% higher in the "thyroxine + iodine" than in the "thyroxine" group (1.91 mU/L vs. 1.34 mU/L). Moreover, 8.77% of newborns in the "thyroxine + iodine" group had TSH > 5 mIU/L. CONCLUSIONS: We did not find evidence for a positive influence of iodine supplementation on thyroid function of either hypothyroid pregnant women sufficiently treated with L-thyroxine or their neonates. (Endokrynol Pol 2016; 67 (4): 367-374). PMID- 27387244 TI - Diagnostics of SHOX gene rearrangement in 46,XX women with idiopathic short stature. AB - INTRODUCTION: The SHOX gene has been mapped at the pseudoautosomal region 1 (PAR1) of chromosomes X (Xp22.33) and Y (Yp11.32). The loss of SHOX gene functionality is assumed to be responsible for the Leri-Weill syndrome formation and the disproportionate short stature (DSS). The SHOX gene rearrangements constitute the majority of cases of gene functionality loss. Therefore, a practical application of the method, which allows for the diagnostics of the gene rearrangements, becomes a primary issue. With such an assumption, the MLPA technique (multiplex ligation - dependent probe amplification) becomes the method of choice. MATERIAL AND METHODS: DNA samples were evaluated in the study by means of the MLPA method. The DNA was isolated from peripheral blood of sixty-three (63) 46,XX patients with short stature. RESULTS: Out of the examined patients, deletions within the SHOX gene were found in five (5) patients, and duplication at the PAR1 regulatory region of the SHOX gene in one (1) case. CONCLUSIONS: The obtained results confirm the opinion that the MLPA method, while enabling the diagnostics of the etiopathogenetic factor of short stature, identified in approximately 9.5% of cases, is a useful tool in the diagnostics of SHOX gene deletion and duplication. (Endokrynol Pol 2016; 67 (4): 397-402). PMID- 27387246 TI - Growth hormone, insulin-like growth factor system and carcinogenesis. AB - The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414-426). PMID- 27387245 TI - Treatment of severe life threatening hypocalcemia with recombinant human teriparatide in patients with postoperative hypoparathyroidism - a case series. AB - INTRODUCTION: Hypocalcaemia is a common postoperative complication, both after the resection of parathyroid adenoma associated with primary hyperparathyroidism and after total thyroidectomy due to thyroid cancer or nodular goitre. For a few years, in patients with postoperative hypoparathyroidism and severe hypocalcaemia, who cannot discontinue intravenous calcium preparations even with the use of high vitamin D doses, attempts have been made to add recombinant human parathormone (rhPTH) to the treatment schedule. In this work, for the first time in Poland, we demonstrate the potential use of teriparatide for the treatment of severe hypocalcaemia based on three different cases of postoperative hypoparathyroidism. MATERIAL AND METHODS: Case 1. Female (52) with postoperative hypoparathyroidism, after total thyroidectomy and the removal of lower left parathyroid gland due to hyperparathyroidism, several weeks after the surgery still required intravenous calcium infusions because of tetany symptoms. Just one month of teriparatide treatment at 20 MUg/0.08 mL given in daily subcutaneous injections proved sufficient to control calcium levels with oral calcium and vitamin D preparations during the next few days until total resolution of hypocalcaemia symptoms and the achievement and maintenance of laboratory normocalcaemia in the following weeks. CASE 2: Female (33) with hypoparathyroidism following total thyroidectomy in 1996 because of papillary thyroid cancer, with congenital tubulopathy associated with renal loss of calcium and magnesium, and the symptoms of tetany recurring since the day of surgery, requiring intravenous calcium administration every 2-3 days. Currently, the patient has been hospitalised because of venous port infection, the only venous access, which made intravenous therapy impossible. Because of the life threatening condition of the patient, bridging teriparatide treatment was prepared (20 MUg/0.08 mL). Complete resolution of clinical symptoms of hypocalcaemia was obtained with teriparatide doses given every 8-12 hours, which made dose reduction possible. Case 3. Female (52) after major oncological surgery because of laryngopharyngeal and cervical oesophageal cancer with the removal of parathyroid glands, fed through PEG, was admitted to hospital with the symptoms of tetany. Despite treatment intensification, the patient experienced a hypocalcaemic crisis during hospitalisation. Teriparatide treatment at 2 * 20 MUg/day resulted in the resolution of tetany symptoms, with gradual normalisation of calcium-phosphate balance parameters during the following days. CONCLUSIONS: Based on the analysis of these cases, the conclusion was drawn that the use of recombinant human teriparatide allows for the control of severe hypocalcaemia requiring intravenous infusions of calcium in patients with postoperative hypoparathyroidism. (Endokrynol Pol 2016; 67 (4): 403-412). PMID- 27387247 TI - Molecular pathways of human adrenocortical carcinoma - translating cell signalling knowledge into diagnostic and treatment options. AB - Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/- chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. (Endokrynol Pol 2016; 67 (4): 427-440). PMID- 27387248 TI - Gender-related voice problems in transsexuals - therapeutical demands. AB - The paper presents a case study of a transsexual patient who underwent a voice pitch elevation surgery performed in Poland for the first time. The human voice is a reflection of the working of hormones and human psyche. This fact is of particular importance in transsexualism, a disorder consisting in incongruence between the individual's biological sex and their identified gender. For many transsexual people, especially of the MTF (male to female) type, who have undergone hormonal and surgical sex change, the voice still presents a major problem, causing difficulties in everyday life. Hormonal treatment does not influence feminisation of the larynx. In the described MTF case, the patient's low androphonic voice was perceived as a male voice. In order to feminise the patient's voice a phonosurgical procedure was performed: the length of the vibrating portion of the vocal folds was shortened by over 50% of their total length by means of suturing of the anterior part of the vocal fold. As a result of the surgical treatment the pitch of voice was raised considerably, with F0 of spoken voice increased from 109 Hz to 209 Hz. The voice range also changed towards female tones, from 59-146 Hz to 148-343 Hz. Pitch elevation positively influenced the patient's subjective voice assessment: total score of the Voice Handicap Index (VHI) improved from 99 to 19 points, and the score of its emotional sub-scale: 39 and 2 points, respectively. The described case of a surgical male-to-female voice change presents one of the dilemmas faced by modern medicine. (Endokrynol Pol 2016; 67 (4): 452-455). PMID- 27387249 TI - Cushing's syndrome due to ectopic ACTH secretion. AB - Cushing's syndrome (CS) is defined as a constellation of clinical signs and symptoms occurring due to hypercortisolism. Cortisol excess may be endogenous or exogenous. The most common cause of CS is glucocorticoid therapy with supraphysiological (higher than in the case of substitution) doses used in various diseases (e.g. autoimmune). One possible CS cause is ectopic (extra pituitary) ACTH secretion (EAS) by benign or malignant tumours. Since its first description in 1963, EAS aetiology has changed, i.e. as well as small cell lung cancer (SCLC), higher incidence in other malignancies has been reported. Ectopic ACTH secretion symptoms are usually similar to hypercortisolism symptoms due to other causes. A clinical suspicion of CS requires laboratory investigations. There is no single and specific laboratory test for making a CS diagnosis, and therefore multiple dynamic tests should be ordered. A combination of multiple laboratory noninvasive and invasive tests gives 100% sensitivity and 98% specificity for EAS diagnosis. If the EAS is caused by localised malignancy, surgery is the optimal treatment choice. Radical tumour excision may be performed in 40% of patients, and 80% of them are cured of the disease. The authors present an interesting clinical case of EAS, which is always a huge diagnostic challenge for clinicians. (Endokrynol Pol 2016; 67 (4): 458-464). PMID- 27387250 TI - Comparative Analysis of DNA-Binding Selectivity of Hairpin and Cyclic Pyrrole Imidazole Polyamides Based on Next-Generation Sequencing. AB - Many long pyrrole-imidazole polyamides (PIPs) have been synthesized in the search for higher specificity, with the aim of realizing the great potential of such compounds in biological and clinical areas. Among several types of PIPs, we designed and synthesized hairpin and cyclic PIPs targeting identical sequences. Bind-n-Seq analysis revealed that both bound to the intended sequences. However, adenines in the data analyzed by the previously reported Bind-n-Seq method appeared to be significantly higher in the motif ratio than thymines, even though the PIPs were not expected to distinguish A from T. We therefore examined the experimental protocol and analysis pipeline in detail and developed a new method based on Bind-n-Seq motif identification with a reference sequence (Bind-n-Seq MR). High-throughput sequence analysis of the PIP-enriched DNA data by Bind-n-Seq MR presented A and T comparably. Surface plasmon resonance assays were performed to validate the new method. PMID- 27387251 TI - Modeling the Growth of Epiphytic Bacteria on Kale Treated by Thermosonication Combined with Slightly Acidic Electrolyzed Water and Stored under Dynamic Temperature Conditions. AB - The growth of epiphytic bacteria (aerobic mesophilic bacteria or Pseudomonas spp.) on kale was modeled isothermally and validated under dynamic storage temperatures. Each bacterial count on kale stored at isothermal conditions (4 to 25 degrees C) was recorded. The results show that maximum growth rate (MUmax ) of both epiphytic bacteria increased and lag time (lambda) decreased with increasing temperature (P < 0.05). The maximum population density (Nmax ) of Pseudomonas spp. was significantly greater than that of aerobic mesophilic bacteria, particularly in treated samples and/or at 4 and 10 degrees C (P < 0.05). The relationship between MUmax of both epiphytic bacteria and temperature was linear (R(2) > 0.97), whereas lower R(2) > 0.86 and R(2) > 0.87 was observed for the lambda and Nmax , respectively. The overall predictions of both epiphytic bacterial growths under nonisothermal conditions with temperature abuse of 15 degrees C agreed with the observed data, whereas those with temperature abuse of 25 degrees C were greatly overestimated. The appropriate parameter q0 (physiological state of cells), therefore, was adjusted by a trial and error to fit the model. This study demonstrates that the developed model was able to predict accurately epiphytic bacterial growth on kale stored under nonisothermal conditions particularly those with low temperature abuse of 15 degrees C. PMID- 27387252 TI - Investigating the dynamics of surface-immobilized DNA nanomachines. AB - Surface-immobilization of molecules can have a profound influence on their structure, function and dynamics. Toehold-mediated strand displacement is often used in solution to drive synthetic nanomachines made from DNA, but the effects of surface-immobilization on the mechanism and kinetics of this reaction have not yet been fully elucidated. Here we show that the kinetics of strand displacement in surface-immobilized nanomachines are significantly different to those of the solution phase reaction, and we attribute this to the effects of intermolecular interactions within the DNA layer. We demonstrate that the dynamics of strand displacement can be manipulated by changing strand length, concentration and G/C content. By inserting mismatched bases it is also possible to tune the rates of the constituent displacement processes (toehold-binding and branch migration) independently, and information can be encoded in the time-dependence of the overall reaction. Our findings will facilitate the rational design of surface immobilized dynamic DNA nanomachines, including computing devices and track-based motors. PMID- 27387254 TI - In vitro gastrointestinal resistance of Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 in soy and/or milk-based synbiotic apple ice creams. AB - The viability and resistance to simulated gastrointestinal (GI) conditions of Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 in synbiotic ice creams, in which milk was replaced by soy extract and/or whey protein isolate (WPI) with inulin, were investigated. The ice creams were showed to be satisfactory vehicles for La-5 and Bb-12 (populations around 7.5logCFU/g), even after the whole storage period (84days/-18 degrees C). In all formulations, the propidium monoazide qPCR (PMA-qPCR) analysis demonstrated that probiotics could resist the in vitro GI assay, with significant survival levels, achieving survival rates exceeding 50%. Additionally, scanning electron microscopy images evidenced cells with morphological differences, suggesting physiological changes in response to the induced stress during the in vitro assay. Although all formulations provided resistance to the probiotic strains under GI stress, the variation found in probiotic survival suggests that GI tolerance is indeed affected by the choice of the food matrix. PMID- 27387253 TI - Androgen excess: Investigations and management. AB - Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5alpha-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response. PMID- 27387255 TI - The perspectives of adults with aphasia and their team members regarding the importance of nine life areas for rehabilitation: a pilot investigation. AB - OBJECTIVES: Client-centred rehabilitation implies that persons with aphasia and their significant others are actively involved in all decisions regarding rehabilitation, including the setting of rehabilitation priorities and goals. This study aimed to describe and compare the perspectives of adults with aphasia, their significant others and their speech-language pathologists (SLPs) regarding the importance of nine life areas for the rehabilitation of adults with aphasia. METHOD: A total of 15 adults with expressive aphasia rated the importance of nine life areas using the Talking MatsTM framework. A questionnaire was used to obtain the ratings of 15 of their significant others and the 15 SLPs treating them. RESULTS: Most life areas were rated as important to work on in rehabilitation by most participants. The adults with aphasia rated the areas as important more frequently than their significant others and SLPs. All participants rated Communication as important. Statistically significant differences were noted for three of the nine life areas. DISCUSSION: The life areas which the participants were questioned about seem to provide a good starting point for rehabilitation teams to find common ground for collaborative goal setting. The Talking MatsTM approach allowed adults with aphasia to participate in the process. It can be a useful tool to promote client-centred rehabilitation for adults with expressive communication difficulties. PMID- 27387256 TI - Effector profiles distinguish formae speciales of Fusarium oxysporum. AB - Formae speciales (ff.spp.) of the fungus Fusarium oxysporum are often polyphyletic within the species complex, making it impossible to identify them on the basis of conserved genes. However, sequences that determine host-specific pathogenicity may be expected to be similar between strains within the same forma specialis. Whole genome sequencing was performed on strains from five different ff.spp. (cucumerinum, niveum, melonis, radicis-cucumerinum and lycopersici). In each genome, genes for putative effectors were identified based on small size, secretion signal, and vicinity to a "miniature impala" transposable element. The candidate effector genes of all genomes were collected and the presence/absence patterns in each individual genome were clustered. Members of the same forma specialis turned out to group together, with cucurbit-infecting strains forming a supercluster separate from other ff.spp. Moreover, strains from different clonal lineages within the same forma specialis harbour identical effector gene sequences, supporting horizontal transfer of genetic material. These data offer new insight into the genetic basis of host specificity in the F. oxysporum species complex and show that (putative) effectors can be used to predict host specificity in F. oxysporum. PMID- 27387257 TI - Impedimetric real-time monitoring of neural pluripotent stem cell differentiation process on microelectrode arrays. AB - In today's neurodevelopment and -disease research, human neural stem/progenitor cell-derived networks represent the sole accessible in vitro model possessing a primary phenotype. However, cultivation and moreover, differentiation as well as maturation of human neural stem/progenitor cells are very complex and time consuming processes. Therefore, techniques for the sensitive non-invasive, real time monitoring of neuronal differentiation and maturation are highly demanded. Using impedance spectroscopy, the differentiation of several human neural stem/progenitor cell lines was analyzed in detail. After development of an optimum microelectrode array for reliable and sensitive long-term monitoring, distinct cell-dependent impedimetric parameters that could specifically be associated with the progress and quality of neuronal differentiation were identified. Cellular impedance changes correlated well with the temporal regulation of biomolecular progenitor versus mature neural marker expression as well as cellular structure changes accompanying neuronal differentiation. More strikingly, the capability of the impedimetric differentiation monitoring system for the use as a screening tool was demonstrated by applying compounds that are known to promote neuronal differentiation such as the gamma-secretase inhibitor DAPT. The non-invasive impedance spectroscopy-based measurement system can be used for sensitive and quantitative monitoring of neuronal differentiation processes. Therefore, this technique could be a very useful tool for quality control of neuronal differentiation and moreover, for neurogenic compound identification and industrial high-content screening demands in the field of safety assessment as well as drug development. PMID- 27387258 TI - A ratiometric fluorescence RRE RNA-targeted assay for a new fluorescence ligand. AB - The Rev protein regulates HIV-1 gene expression. Small ligands that bind to the Rev response element (RRE) RNA would inhibit Rev function and suppress HIV-1 replication. A novel ratiometric fluorescence assay was applied in the present study to monitor ligand-RNA interactions by using red-emitting CdTe quantum dots (QDs) coated with silica as a reference. A small fluorescence ligand, ICR 191, was found to interact with RRE at the Rev binding site and compete with the Rev peptide. After adding red-emitting QDs to the interaction system, it was observed that ICR 191 did not fluoresce upon the addition of RRE, and fluorescence recovered when ICR 191 was displaced by a Rev model peptide, whereas the fluorescence of QDs remained constant. Furthermore, variations in the fluorescence ratios between ICR 191 and QDs were exploited to characterize the interactions of Rev with two known antagonists, neomycin B and tobramycin, by using RRE RNA with ICR 191 as a fluorescence indicator. Together, our results demonstrated that ratiometric fluorescence-based nanotechnology applications can be used for ligand-RNA interaction assays. This ICR 191-RRE RNA interaction assay can potentially be developed to build a screening model for assessing antagonists of the Rev binding element in RRE. PMID- 27387259 TI - Highly sensitive sandwich-type SPR based detection of whole H5Nx viruses using a pair of aptamers. AB - In this research, we report highly sensitive and specific sandwich-type SPR-based biosensor for the detection H5Nx whole viruses. A few of aptamers, for the first time, were successfully screened and characterized for whole avian influenza (AI) viruses, H5Nx, by using Multi-GO-SELEX method. The affinities of the aptamers developed in this study were ranged from 8*10(4) to 1*10(4)EID50/ml, and the aptamers IF22, IF23 were found to be specific to H5N1 and H5N8, respectively. In addition, some flexible aptamers IF20, IF15, and IF10 were found to bind to the H5N1 and H5N2, H5N1 and H5N8, or H5N1, H5N2, and H5N8, respectively. Moreover, aptamers IF10 and IF22 were found to bind H5N1 virus simultaneously and confirmed to bind the different site of the same H5N1 whole virus. Therefore, this pair of aptamers, IF10 and IF22, were successfully applied to develop the sandwich-type SPR-based biosensor assay which is rapid, accurate for the detection of AI whole virus from H5N1-infected feces samples. The minimum detectible concentration of H5N1 whole virus was found to be 200 EID50/ml with this sandwich-type detection using the aptamer pair obtained in this study. In addition, the sensitivity of this biosensor was successfully enhanced by using the signal amplification with the secondary aptamer conjugated with gold nanoparticles. PMID- 27387260 TI - Visible-light driven photoelectrochemical immunosensor for insulin detection based on MWCNTs@SnS2@CdS nanocomposites. AB - In this work, a label-free photoelectrochemical (PEC) immunosensor was developed for ultrasensitive detection of insulin based on MWCNTs@SnS2@CdS nanocomposites. As graphene-like 2D nanomaterial, SnS2 nanosheets loaded on the conducting framework of multi-walled carbon nanotubes (MWCNTs) were adopted for the construction of immunosensor for the first time, providing a favorable substrate for in-situ growth of CdS nanocrystal that had suitable band structure matching well with SnS2. The well-matched band structure of these two metal sulfides effectively inhibited the recombination of photogenerated electron-hole pairs, thus improving the photo-to-current conversion efficiency. Besides, the introduction of MWCNTs facilitated electron transfer across the surface of electrodes, leading to a further increment of photocurrent. The as constructed label-free PEC immunosensor based on MWCNTs@SnS2@CdS nanocomposites exhibited excellent PEC performance for the detection of insulin. The concentrations of insulin could be directly detected based on the decrement of photocurrent that was brought by the increased steric hindrances due to the formation of antigen antibody immunocomplexes. Under the optimal conditions, the PEC immunosensor had a sensitive response to insulin in a linear range of 0.1pgmL(-1) to 5ngmL(-1) with a detection limit of 0.03pgmL(-1). Meanwhile, good stability and selectivity were achieved as well. The design and fabrication of this PEC immunosensor based on MWCNTs@SnS2@CdS nanocomposites not only provided an ideal platform for the detection of insulin, but also opened up a new avenue for the development of immunosensor for some other biomarkers analysis. PMID- 27387261 TI - Single-walled carbon nanotubes covalently functionalized with polytyrosine: A new material for the development of NADH-based biosensors. AB - We report for the first time the use of single-walled carbon nanotubes (SWCNT) covalently functionalized with polytyrosine (Polytyr) (SWCNT-Polytyr) as a new electrode material for the development of nicotinamide adenine dinucleotide (NADH)-based biosensors. The oxidation of glassy carbon electrodes (GCE) modified with SWCNT-Polytyr at potentials high enough to oxidize the tyrosine residues have allowed the electrooxidation of NADH at low potentials due to the catalytic activity of the quinones generated from the primary oxidation of tyrosine without any additional redox mediator. The amperometric detection of NADH at 0.200V showed a sensitivity of (217+/-3)uAmM(-1)cm(-2) and a detection limit of 7.9nM. The excellent electrocatalytic activity of SWCNT-Polytyr towards NADH oxidation has also made possible the development of a sensitive ethanol biosensor through the immobilization of alcohol dehydrogenase (ADH) via Nafion entrapment, with excellent analytical characteristics (sensitivity of (5.8+/-0.1)uAmM(-1)cm(-2), detection limit of 0.67uM) and very successful application for the quantification of ethanol in different commercial beverages. PMID- 27387263 TI - Group Testing with Multiple Inhibitor Sets and Error-Tolerant and Its Decoding Algorithms. AB - In this article, we advance a new group testing model [Formula: see text] with multiple inhibitor sets and error-tolerant and propose decoding algorithms for it to identify all its positives by using [Formula: see text]-disjunct matrix. The decoding complexity for it is [Formula: see text], where [Formula: see text]. Moreover, we extend this new group testing to threshold group testing and give the threshold group testing model [Formula: see text] with multiple inhibitor sets and error-tolerant. By using [Formula: see text]-disjunct matrix, we propose its decoding algorithms for gap g = 0 and g > 0, respectively. Finally, we point out that the new group testing is the natural generalization for the clone model. PMID- 27387262 TI - A label-free photoelectrochemical aptasensor for bisphenol A based on surface plasmon resonance of gold nanoparticle-sensitized ZnO nanopencils. AB - A simple and novel photoelectrochemical (PEC) aptasensor for selective detection of bisphenol A (BPA) was developed using surface plasmon resonance of Au nanoparticles activated ZnO nanopencils. With the irradiation of simulated light, the increased photocurrent of nano-Au/ZnO than that of pure ZnO nanopencil is induced by the hot electrons from excited Au nanoparticles. The perfect selectivity is attributed to the specific binding of BPA to its aptamer. With the addition of BPA, the conformation of aptamer changed to a G-quadruplex structure, which resulted in the blockages of photogenerated electron-transfer channels. Based on the above mechanisms and the optimized conditions, the assembled PEC aptasensor was linear with the concentration of BPA in the range of 1-1000nmolL( 1) with a detection limit of 0.5nmolL(-1). The presence of the same concentration and similar structure of other organics did not interfere in the detection of BPA and the recovery was between 96.2% and 108.4%. It has been successfully applied to the detection of BPA in drinking water and liquid milk samples. This PEC aptasensor has good performances in novelty, selectivity, sensitivity and low cost, and it provides an alternative approach to the detection of BPA. PMID- 27387264 TI - A pilot study combining Go4Life(r) materials with an interactive voice response system to promote physical activity in older women. AB - Telephone-based interactive voice response (IVR) systems could be an effective tool for promotion of physical activity among older women. To test IVR feasibility, we enrolled 30 older women in a 10-week physical activity intervention designed around National Institute on Aging (NIA) Go4Life(r) educational materials with IVR coaching. Participants (mean age = 76 years) significantly increased physical activity by a mean 79 +/- 116 (SD) minutes/week (p < .001). Participants reported that the Go4Life(r) materials, pedometer, and IVR coaching (70% reported easy technology) were useful tools for change. This pilot study demonstrates IVR acceptability as an evidence-based physical activity program for older women. PMID- 27387265 TI - Genotoxic evaluation of Halfenprox using the human peripheral lymphocyte micronucleus assay and the Ames test. AB - The genotoxicity and mutagenicity of Halfenprox, a synthetic pyrethroid insecticide and acaricide, was assessed using two standard genotoxicity assays of the Salmonella typhimurium mutagenicity assay (Ames test) and in vitro micronucleus (MN) assay in human peripheral lymphocytes. In the Ames test, Salmonella strains TA98 and TA100 were treated with or without S9 fraction. The doses of Halfenprox were 6.25, 12.5, 25, 50, and 100 MUg/plate and test materials were dissolved in DMSO. The concentrations of Halfenprox did not show mutagenic activity on both strains with and without S9 fraction. The MN assay was used to investigate the genotoxic effects of Halfenprox in human peripheral lymphocytes treated with 250, 500, 750, and 1000 MUg/ml concentrations of Halfenprox for 24 and 48 h, and at 1000 MUg/ml the concentration was significantly increased and the MN formation was compared with the negative control for both treatment periods. In addition, a significant decrease of the nuclear devision index (NDI) values at the higher concentrations of Halfenprox and at both treatment periods was observed. PMID- 27387267 TI - Interstitial lung disease in systemic sclerosis: progress in screening and early diagnosis. AB - PURPOSE OF REVIEW: Interstitial lung disease (ILD) is the major determinant of morbidity and mortality in systemic sclerosis (SSc). In highly selected SSc patients, it was recently shown that stem cell therapy early in the disease course improved survival and reduced the extent of ILD, providing a rationale for early ILD detection strategies in this disease. Here, we review recent progress on ILD screening and early diagnosis in SSc. RECENT FINDINGS: Two studies showed that over 60% of unselected SSc cases with ILD by high-resolution computer tomography (HRCT) had normal range pulmonary function tests (PFTs); indicating poor performance of PFTs for ILD screening purposes. Serial, paired HRCT and PFT analyses indicated that screening by HRCT at baseline predicted risk for lung fibrosis development, progression rate of fibrosis and PFT decline. Analyses of circulating biomarkers, like CCL18, and nonradiating lung imaging modalities, like ultrasound and MRI, showed promise as tools for early ILD detection; but further work is needed. SUMMARY: Prospective cohort data indicated poor performance of PFT as a stand-alone method for ILD screening. Lung HRCT appeared promising, but radiation is an issue. Promising biomarker data indicate the possibility of new ILD screening algorithms in SSc. PMID- 27387266 TI - Progress in understanding the diagnostic and pathogenic role of autoantibodies associated with systemic sclerosis. AB - PURPOSE OF REVIEW: At the time of diagnosis, systemic sclerosis (SSc) is often well established with significant irreversible tissue and organ damage. Definitions of 'early SSc' have been proposed, which include the presence of SSc associated autoantibodies. In addition, functional autoantibodies that are believed to be involved in SSc pathogenesis need to be considered. In this review, recent advances in the diagnostic utility and pathogenic role of autoantibodies in early SSc are summarized. Moreover, we propose a clinical care pathway illustrating how autoantibody testing along with key clinical features can be used to make an earlier diagnosis of SSc. RECENT FINDINGS: Recent evidence has helped to develop a clearer understanding of the natural history, early clinical features, and autoantibodies that are predictors of SSc. The role of functional autoantibodies is leading to innovative approaches to evidence-based interventions and therapies that are based on mechanisms of disease. SUMMARY: Despite substantial advances, the high morbidity and mortality that currently characterizes SSc can largely be attributed to a delay in diagnosis, gaps in our understanding of the role of autoantibodies in early disease, and limited effective therapeutic options. An early and accurate diagnosis of SSc and use of autoantibody testing embedded in evidence-based clinical care pathways will help improve SSc-associated clinical outcomes and healthcare expenditures. PMID- 27387268 TI - Photo-induced electron transfer in a diamino-substituted Ru(bpy)3[PF6]2 complex and its application as a triplet photosensitizer for nitric oxide (NO)-activated triplet-triplet annihilation upconversion. AB - A system demonstrating Nitric Oxide (NO) activated Triplet-Triplet Annihilation (TTA) upconversion has been devised, based on a substituted [Ru(II)(bpy)3](PF6)2 complex (bpy = 2,2'-dipyridine) bearing a single 1,2-diaminophenyl moiety as an NO activatable triplet photosensitizer (Ru-1), and 9,10-diphenylanthracene (DPA) as a triplet acceptor/emitter. The excited triplet state of Ru-1 is significantly quenched (PhiT~ 22%) by a Photoinduced Electron Transfer (PET) reaction, as confirmed by steady state phosphorescence and transient absorption spectroscopy, and hence Ru-1 does not function as a TTA upconversion sensitizer. However, in the presence of NO/O2, the 1,2-diaminophenyl group of Ru-1 is transformed into a benzotriazole. This inhibits PET, and the triplet state quantum yield is increased to ca. 85%, switching on the TTA upconversion process which increases by 10-fold. These processes were studied using a combination of steady state and time-resolved luminescence together with transient absorption spectroscopy on the nanosecond and femtosecond timescales. The energy level of the charge transfer state (CTS) for Ru-1 was also obtained electrochemically, supporting the PET mechanism of triplet state quenching and hence the lack of TTA upconversion with Ru-1. PMID- 27387269 TI - Explaining Constrains Causal Learning in Childhood. AB - Three experiments investigate how self-generated explanation influences children's causal learning. Five-year-olds (N = 114) observed data consistent with two hypotheses and were prompted to explain or to report each observation. In Study 1, when making novel generalizations, explainers were more likely to favor the hypothesis that accounted for more observations. In Study 2, explainers favored a hypothesis that was consistent with prior knowledge. Study 3 pitted a hypothesis that accounted for more observations against a hypothesis consistent with prior knowledge. Explainers were more likely to base generalizations on prior knowledge. Findings suggest that attempts to explain drive children to evaluate hypotheses using features of "good" explanations, or those supporting generalizations with broad scope, as informed by children's prior knowledge and observations. PMID- 27387270 TI - A lab-on-a-chip device for investigating the fusion process of olfactory ensheathing cell spheroids. AB - Understanding the process of fusion of olfactory ensheathing cell spheroids will lead to improvement of cell transplantation therapies to repair spinal cord injuries. The successful fusion of transplanted spheroids will enable alternative transplantation strategies to be developed for in vivo applications. This paper describes the use of a microfluidic device to trap and fuse olfactory ensheathing cell spheroids. The velocity, the pressure distribution in the device were simulated numerically to predict the trapping location. The simulation predicted the optimum flow rates for trapping the spheroids in the later experiments. Simulated particle trajectories were verified experimentally with tracing of fluorescent micro particles. The fusion process of the spheroids was investigated over a period of 48 hours. The microfluidic platform presented here can be used for testing potential drugs that can promote the fusion process and improve the transplantation therapy. PMID- 27387271 TI - Skilled nursing facility placement in hospitalized elderly patients with colon cancer. AB - BACKGROUND: The current study sought to determine predictive risk factors and inpatient resource utilization associated with discharge to skilled nursing facility (SNF) in hospitalized elderly patients with colon cancer. MATERIALS AND METHODS: Inpatient data from U.S. community hospital discharges from 2003 to 2011 was analyzed in a retrospective cohort study using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS). Subjects included hospitalized postoperative colon cancer patients over age of 65 (N = 98,797). RESULTS: The proportion of elderly colon cancer patients discharged to a SNF increased by 16.67% from 2003 to 2011 (18-21%). Elderly patients discharged to a SNF had increased hospitalization costs (+$10,293.70, p < 0.01) compared to elderly colon cancer patients discharged home. Hospitalization predictive risk factors associated with SNF placement include age above 75 (OR, 4.07; 95% CI, 3.90, 4.25; p < 0.01), paralysis (OR, 3.60; 95% CI, 3.06-4.23; p < 0.01), length of stay (LOS) 10 days or more (OR, 3.00; 95% CI, 2.88-3.13; p < 0.01), psychoses (OR, 2.91; 95% CI, 2.56-3.32; p < 0.01), and neurological disorders (OR, 2.34; 95% CI, 2.17-2.52; p < 0.01). CONCLUSIONS: Despite increased costs and worse clinical outcomes associated with SNF placement, over 40% increase of hospital discharge to SNF should be anticipated from this population over the next 20 years. Neurologic and psychiatric comorbidities have significantly negative clinical impacts and increase the likelihood of colon cancer patients' discharge to a SNF. PMID- 27387272 TI - Detection and Quantification of Differentially Culturable Tubercle Bacteria in Sputum from Patients with Tuberculosis. AB - RATIONALE: Recent studies suggest that baseline tuberculous sputum comprises a mixture of routinely culturable and differentially culturable tubercle bacteria (DCTB). The latter seems to be drug tolerant and dependent on resuscitation promoting factors (Rpfs). OBJECTIVES: To further explore this, we assessed sputum from patients with tuberculosis for DCTB and studied the impact of exogenous culture filtrate (CF) supplementation ex vivo. METHODS: Sputum samples from adults with tuberculosis and HIV-1 and adults with no HIV-1 were used for most probable number (MPN) assays supplemented with CF and Rpf-deficient CF, to detect CF-dependent and Rpf-independent DCTB, respectively. MEASUREMENTS AND MAIN RESULTS: In 110 individuals, 19.1% harbored CF-dependent DCTB and no Rpf independent DCTB. Furthermore, 11.8% yielded Rpf-independent DCTB with no CF dependent DCTB. In addition, 53.6% displayed both CF-dependent and Rpf independent DCTB, 1.8% carried CF-independent DCTB, and 13.6% had no DCTB. Sputum from individuals without HIV-1 yielded higher CF-supplemented MPN counts compared with counterparts with HIV-1. Furthermore, individuals with HIV-1 with CD4 counts greater than 200 cells/mm3 displayed higher CF-supplemented MPN counts compared with participants with HIV-1 with CD4 counts less than 200 cells/mm3. CF supplementation allowed for detection of mycobacteria in 34 patients with no culturable bacteria on solid media. Additionally, the use of CF enhanced detection of sputum smear-negative individuals. CONCLUSIONS: These observations demonstrate a novel Rpf-independent DCTB population in sputum and reveal that reduced host immunity is associated with lower prevalence of CF-responsive bacteria. Quantification of DCTB in standard TB diagnosis would be beneficial because these organisms provide a putative biomarker to monitor treatment response and risk of disease recurrence. PMID- 27387273 TI - Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice. AB - CONTEXT: Silymarin is the main flavonoid extracted from milk thistle, which has been used to treat liver diseases. OBJECTIVE: The in vivo effect of silymarin on HFD-induced insulin resistance and fatty liver in mice was studied. MATERIALS AND METHODS: Male C57BL/6 mice were fed with high-fat diet (HFD) to induce obesity and insulin resistance and treated with 30, 60 mg/kg silymarin for 18 days. Food intake, body weight and the content/histology of epididymal fat and liver tissue were examined; the content of lipids, AST, ALT and inflammatory cytokines in serum were estimated. RESULTS: Administration of silymarin caused bodyweight loss in diet induced obesity (DIO) mice (HFD group: 47.7 g, 60 mg/kg group: 43.0 g) while the food intake remain unchanged. Silymarin (60 mg/kg) significantly reduced the epididymal fat mass (from 1.75 g to 1.12 g). Elevated plasma lipids (TC 6.1 mM, TG 1.3 mM, LDL 1.2 mM) in DIO mice were all suppressed by silymarin (TC 4.5 mM, TG 0.89 mM, LDL 0.9 mM), as well as insulin (5.1 ng/ml in HFD group to 2.0 ng/ml (60 mg/kg silymarin). Examination of cytokine levels (TNF-alpha, IL 1beta and IL-6) in each group proved that silymarin treatment significantly decreased inflammation in DIO mice. Finally, silymarin effectively protected liver from HFD-induced injury as evidenced by decreasing histological damage and reducing ALT and AST levels, as follows: ALT; 47.4 U/L in HFD group to 28.4 U/L (60 mg/kg silymarin); AST; 150.1 U/L in HFD group to 88.1 U/L (60 mg/kg silymarin) in serum. DISCUSSION AND CONCLUSION: Our results suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance. PMID- 27387274 TI - The role of graphene formed on silver nanowire transparent conductive electrode in ultra-violet light emitting diodes. AB - This paper reports a highly reliable transparent conductive electrode (TCE) that integrates silver nanowires (AgNWs) and high-quality graphene as a protecting layer. Graphene with minimized defects and large graphene domains has been successfully obtained through a facile two-step growth approach. Ultraviolet light emitting diodes (UV-LEDs) were fabricated with AgNWs or hybrid electrodes where AgNWs were combined with two-step grown graphene (A-2GE) or conventional one-step grown graphene (A-1GE). The device performance and reliability of the UV LEDs with three different electrodes were compared. The A-2GE offered high figure of merit owing to the excellent UV transmittance and reduced sheet resistance. As a consequence, the UV-LEDs made with A-2GE demonstrated reduced forward voltage, enhanced electroluminescence (EL) intensity, and alleviated efficiency droop. The effects of joule heating and UV light illumination on the electrode stability were also studied. The present findings prove superior performance of the A-2GE under high current injection and continuous operation of UV LED, compared to other electrodes. From our observation, the A-2GE would be a reliable TCE for high power UV-LEDs. PMID- 27387275 TI - Evaluation Of freehand high-resolution 3-dimensional ultrasound of the median nerve. AB - INTRODUCTION: In this study we evaluated freehand 3D ultrasound (3DUS) of the median nerve in comparison to 2D ultrasound (2DUS) and assessed the influence of tilting the transversal plane on cross-sectional area (CSA) measurement. METHODS: Two examiners investigated the median nerves of 22 healthy subjects over a distance of 20 cm using 3DUS. Image quality and CSA were assessed at random points within the virtual 3D volume and compared with 2DUS. RESULTS: Image quality within the virtual 3D volume was good/sufficient/poor in 53.0%/40.2%/6.8% (examiner 1) and 21.6%/69.6%/8.8% (examiner 2), respectively. CSA measurements with 3DUS were smaller than with 2DUS (-12% and -17%; Wilcoxon test, P < 0.001). Interrater agreement for 3DUS and intermethod agreement between 2DUS and 3DUS were moderate. Stepwise tilting of the transversal plane increased CSA significantly. CONCLUSION: Freehand 3DUS of the median nerve over 20 cm is feasible and may help overcome some of the limitations and pitfalls of 2DUS. Muscle Nerve 55: 206-212, 2017. PMID- 27387276 TI - Photo-Fenton treatment of valproate under UVC, UVA and simulated solar radiation. AB - The abatement of valproic acid sodium salt (VA) via photo-Fenton process was investigated to evaluate the effect of irradiation type. Three different light sources have been used: UVA (black light blue lamps, BLB reactor), UVC (UVC reactor) and simulated sunlight in a Solarbox (SB). Using the highest concentrations of Fe2+ (10mgL-1) and H2O2 (150mgL-1), 100% of VA degradation was observed in BLB and UVC devices, and 89.7% in Solarbox. Regarding mineralization, 67.4% and 76.4% of TOC conversion were achieved in BLB and UVC, respectively. In Solarbox, mineralization was negligible. Treated solutions under UVA or UVC radiation became biodegradable (BOD5/COD>=0.25), which was not observed in Solarbox where BOD5/COD achieved was only 0.20. Regarding to toxicity (Vibrio Fischeri method), all processes have promoted the overall toxicity reduction of VA solution. Transformation products were identified by a LC-ESI-TOF mass spectrometer, and degradation pathways were proposed. Operating costs and the energy needed by mg of VA removed were estimated and compared, for the different installations, showing that UVA can remove around 3 times more VA than SB and 2 times more VA than UVC, under the same conditions. PMID- 27387277 TI - A vaccine combining two Leishmania braziliensis proteins offers heterologous protection against Leishmania infantum infection. AB - In the present study, two Leishmania braziliensis proteins, one hypothetical and the eukaryotic initiation factor 5a (EiF5a), were cloned and used as a polyproteins vaccine for the heterologous protection of BALB/c mice against infantum infection. Animals were immunized with the antigens separately or in association, and in both cases saponin was used as an adjuvant. In the results, spleen cells from mice inoculated with the individual or polyproteins vaccine and lately challenged produced significantly higher levels of protein- and parasite specific IFN-gamma, IL-12, and GM-CSF, when both a capture ELISA and flow cytometry assays were performed. Evaluating the parasite load by a limiting dilution as well as by RT-PCR, these animals presented significant reductions in the parasite number in all evaluated organs, when compared to the control (saline and saponin) groups. The best protection was reached when the polyproteins vaccine was employed. Protection was associated with the IFN-gamma production against parasite extracts, which was mediated by both CD4(+) and CD8(+) T cells and correlated with the antileishmanial nitrite production. In this context, this vaccine combining two L. braziliensis proteins was able to induce a heterologous protection against VL, and could be considered in future studies to be tested against other Leishmania species or in other mammalian hosts. PMID- 27387278 TI - HMGB1 blockade differentially impacts pulmonary inflammation and defense responses in poly(I:C)/LPS-exposed heart transplant mice. AB - A large number of recipients are in a compromised immune defense condition because of the routine application of immunosuppressive regimens after heart transplantation. Our previous work demonstrated that blockade of high-mobility group box 1 (HMGB1) prolongs the graft survival. Whether and how HMGB1 blockade impacts respiratory responses against pathogen-like challenge in organ transplant recipients when it improves cardiac graft are not elucidated. At the present study, after abdominal heterotopic heart transplantation, the recipient mice were treated with HMGB1 mAb, and then challenged with poly(I:C) or LPS intratracheally on day 7 post transplantation. We found that the level of bronchoalveolar lavage (BAL) HMGB1 was elevated after heart transplantation, and aggravated responses to respiratory tract poly(I:C)/LPS challenge were observed. HMGB1 neutralizing mAb treatment in poly(I:C)-challenged recipient mice alleviated pulmonary histopathological changes, neutrophil infiltration and inflammatory cytokine release, but unaffected the level of IFN-beta, the distribution of CD11b(+)CD27(+)/CD11b(+)CD27(-) NK cell subsets, and CD8(+) T cell responses. In LPS-exposed recipient mice, HMGB1 mAb treatment ameliorated pulmonary inflammatory damage and enhanced the phagocytosis of phagocytic cells. Thus, this study may establish a basis for the application of HMGB1 blockade to improve the outcomes of heart transplant recipients because HMGB1 inhibition ameliorates pulmonary inflammation, but maintains defense-associated responses. PMID- 27387279 TI - Comparison of High, Intermediate, and Low Frequency Shock Wave Lithotripsy for Urinary Tract Stone Disease: Systematic Review and Network Meta-Analysis. AB - OBJECTIVES: To perform a systematic review and network meta-analysis of randomized controlled trials (RCTs) to determine the optimal shock wave lithotripsy (SWL) frequency range for treating urinary stones, i.e., high frequency (100-120 waves/minute), intermediate-frequency (80-90 waves/minute), and low-frequency (60-70 waves/minute) lithotripsy. MATERIALS AND METHODS: Relevant RCTs were identified from electronic databases for meta-analysis of SWL success and complication rates. Using pairwise and network meta-analyses, comparisons were made by qualitative and quantitative syntheses. Outcome variables are provided as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Thirteen articles were included in the qualitative and quantitative synthesis using pairwise and network meta-analyses. On pairwise meta-analyses, comparable inter-study heterogeneity was observed for the success rate. On network meta-analyses, the success rates of low- (OR 2.2; 95% CI 1.5-2.6) and intermediate-frequency SWL (OR 2.5; 95% CI 1.3-4.6) were higher than high frequency SWL. Forest plots from the network meta-analysis showed no significant differences in the success rate between low-frequency SWL versus intermediate frequency SWL (OR 0.87; 95% CI 0.51-1.7). There were no differences in complication rate across different SWL frequency ranges. By rank-probability testing, intermediate-frequency SWL was ranked highest for success rate, followed by low-frequency and high-frequency SWL. Low-frequency SWL was also ranked highest for low complication rate, with high- and intermediate-frequency SWL ranked lower. CONCLUSIONS: Intermediate- and low-frequency SWL have better treatment outcomes than high-frequency SWL when considering both efficacy and complication. PMID- 27387280 TI - Isotope signatures of N2O emitted from vegetable soil: Ammonia oxidation drives N2O production in NH4(+)-fertilized soil of North China. AB - Nitrous oxide (N2O) is a potent greenhouse gas. In North China, vegetable fields are amended with high levels of N fertilizer and irrigation water, which causes massive N2O flux. The aim of this study was to determine the contribution of microbial processes to N2O production and characterize isotopic signature effects on N2O source partitioning. We conducted a microcosm study that combined naturally abundant isotopologues and gas inhibitor techniques to analyze N2O flux and its isotopomer signatures [delta(15)N(bulk), delta(18)O, and SP (intramolecular (15)N site preference)] that emitted from vegetable soil after the addition of NH4(+) fertilizers. The results show that ammonia oxidation is the predominant process under high water content (70% water-filled pore space), and nitrifier denitrification contribution increases with increasing N content. delta(15)N(bulk) and delta(18)O of N2O may not provide information about microbial processes due to great shifts in precursor signatures and atom exchange, especially for soil treated with NH4(+) fertilizer. SP and associated two end-member mixing model are useful to distinguish N2O source and contribution. Further work is needed to explore isotopomer signature stability to improve N2O microbial process identification. PMID- 27387281 TI - Perpetuating the homing endonuclease life cycle: identification of mutations that modulate and change I-TevI cleavage preference. AB - Homing endonucleases are sequence-tolerant DNA endonucleases that act as mobile genetic elements. The ability of homing endonucleases to cleave substrates with multiple nucleotide substitutions suggests a high degree of adaptability in that changing or modulating cleavage preference would require relatively few amino acid substitutions. Here, using directed evolution experiments with the GIY-YIG homing endonuclease I-TevI that targets the thymidylate synthase gene of phage T4, we readily isolated variants that dramatically broadened I-TevI cleavage preference, as well as variants that fine-tuned cleavage preference. By combining substitutions, we observed an ~10 000-fold improvement in cleavage on some substrates not cleaved by the wild-type enzyme, correlating with a decrease in readout of information content at the cleavage site. Strikingly, we were able to change the cleavage preference of I-TevI to that of the isoschizomer I-BmoI which targets a different cleavage site in the thymidylate synthase gene, recapitulating the evolution of cleavage preference in this family of homing endonucleases. Our results define a strategy to isolate GIY-YIG nuclease domains with distinct cleavage preferences, and provide insight into how homing endonucleases may escape a dead-end life cycle in a population of saturated target sites by promoting transposition to different target sites. PMID- 27387283 TI - Mechanical properties of DNA origami nanoassemblies are determined by Holliday junction mechanophores. AB - DNA nanoassemblies have demonstrated wide applications in various fields including nanomaterials, drug delivery and biosensing. In DNA origami, single stranded DNA template is shaped into desired nanostructure by DNA staples that form Holliday junctions with the template. Limited by current methodologies, however, mechanical properties of DNA origami structures have not been adequately characterized, which hinders further applications of these materials. Using laser tweezers, here, we have described two mechanical properties of DNA nanoassemblies represented by DNA nanotubes, DNA nanopyramids and DNA nanotiles. First, mechanical stability of DNA origami structures is determined by the effective density of Holliday junctions along a particular stress direction. Second, mechanical isomerization observed between two conformations of DNA nanotubes at 10-35 pN has been ascribed to the collective actions of individual Holliday junctions, which are only possible in DNA origami with rotational symmetric arrangements of Holliday junctions, such as those in DNA nanotubes. Our results indicate that Holliday junctions control mechanical behaviors of DNA nanoassemblies. Therefore, they can be considered as 'mechanophores' that sustain mechanical properties of origami nanoassemblies. The mechanical properties observed here provide insights for designing better DNA nanostructures. In addition, the unprecedented mechanical isomerization process brings new strategies for the development of nano-sensors and actuators. PMID- 27387282 TI - PCBP2 enables the cadicivirus IRES to exploit the function of a conserved GRNA tetraloop to enhance ribosomal initiation complex formation. AB - The cadicivirus IRES diverges structurally from canonical Type 1 IRESs (e.g. poliovirus) but nevertheless also contains an essential GNRA tetraloop in a subdomain (d10c) that is homologous to poliovirus dIVc. In addition to canonical initiation factors, the canonical Type 1 and divergent cadicivirus IRESs require the same IRES trans-acting factor, poly(C)-binding protein 2 (PCBP2). PCBP2 has three KH domains and binds poliovirus IRES domain dIV in the vicinity of the tetraloop. How PCBP2 binds the cadicivirus IRES, and the roles of PCBP2 and the tetraloop in Type 1 IRES function are unknown. Here, directed hydroxyl radical probing showed that KH1 also binds near the cadicivirus tetraloop. KH2 and KH3 bind adjacently to an IRES subdomain (d10b) that is unrelated to dIV, with KH3 in an inverted orientation. KH3 is critical for PCBP2's binding to this IRES whereas KH1 is essential for PCBP2's function in promoting initiation. PCBP2 enforced the wild-type structure of d10c when it contained minor destabilizing substitutions, exposing the tetraloop. Strikingly, PCBP2 enhanced initiation on mutant IRESs that retained consensus GNRA tetraloops, whereas mutants with divergent sequences did not respond to PCBP2. These studies show that PCBP2 enables the IRES to exploit the GNRA tetraloop to enhance initiation. PMID- 27387284 TI - Post-ExSELEX stabilization of an unnatural-base DNA aptamer targeting VEGF165 toward pharmaceutical applications. AB - A new technology, genetic alphabet expansion using artificial bases (unnatural bases), has created high-affinity DNA ligands (aptamers) that specifically bind to target proteins by ExSELEX (genetic alphabet Expansion for Systematic Evolution of Ligands by EXponential enrichment). We recently found that the unnatural-base DNA aptamers can be stabilized against nucleases, by introducing an extraordinarily stable, unique hairpin DNA (mini-hairpin DNA) and by reinforcing the stem region with G-C pairs. Here, to establish this aptamer generation method, we examined the stabilization of a high-affinity anti-VEGF165 unnatural-base DNA aptamer. The stabilized aptamers displayed significantly increased thermal and nuclease stabilities, and furthermore, exhibited higher affinity to the target. As compared to the well-known anti-VEGF165 RNA aptamer, pegaptanib (Macugen), our aptamers did not require calcium ions for binding to VEGF165 Biological experiments using cultured cells revealed that our stabilized aptamers efficiently inhibited the interaction between VEGF165 and its receptor, with the same or slightly higher efficiency than that of the pegaptanib RNA aptamer. The development of cost-effective and calcium ion-independent high affinity anti-VEGF165 DNA aptamers encourages further progress in diagnostic and therapeutic applications. In addition, the stabilization process provided additional information about the key elements required for aptamer binding to VEGF165. PMID- 27387285 TI - A structural analysis of DNA binding by hSSB1 (NABP2/OBFC2B) in solution. AB - Single-stranded DNA binding proteins (SSBs) play an important role in DNA processing events such as replication, recombination and repair. Human single stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) contains a single oligosaccharide/oligonucleotide binding (OB) domain followed by a charged C terminus and is structurally homologous to the SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus Recent work has revealed that hSSB1 is critical to homologous recombination and numerous other important biological processes such as the regulation of telomeres, the maintenance of DNA replication forks and oxidative damage repair. Since the ability of hSSB1 to directly interact with single-stranded DNA (ssDNA) is paramount for all of these processes, understanding the molecular details of ssDNA recognition is essential. In this study, we have used solution-state nuclear magnetic resonance in combination with biophysical and functional experiments to structurally analyse ssDNA binding by hSSB1. We reveal that ssDNA recognition in solution is modulated by base-stacking of four key aromatic residues within the OB domain. This DNA binding mode differs significantly from the recently determined crystal structure of the SOSS1 complex containing hSSB1 and ssDNA. Our findings elucidate the detailed molecular mechanism in solution of ssDNA binding by hSSB1, a major player in the maintenance of genomic stability. PMID- 27387286 TI - The mechanism of phiC31 integrase directionality: experimental analysis and computational modelling. AB - Serine integrases, DNA site-specific recombinases used by bacteriophages for integration and excision of their DNA to and from their host genomes, are increasingly being used as tools for programmed rearrangements of DNA molecules for biotechnology and synthetic biology. A useful feature of serine integrases is the simple regulation and unidirectionality of their reactions. Recombination between the phage attP and host attB sites is promoted by the serine integrase alone, giving recombinant attL and attR sites, whereas the 'reverse' reaction (between attL and attR) requires an additional protein, the recombination directionality factor (RDF). Here, we present new experimental data on the kinetics and regulation of recombination reactions mediated by phiC31 integrase and its RDF, and use these data as the basis for a mathematical model of the reactions. The model accounts for the unidirectionality of the attP * attB and attL * attR reactions by hypothesizing the formation of structurally distinct, kinetically stable integrase-DNA product complexes, dependent on the presence or absence of RDF. The model accounts for all the available experimental data, and predicts how mutations of the proteins or alterations of reaction conditions might increase the conversion efficiency of recombination. PMID- 27387287 TI - Systematic Evaluation of Industrial, Commercial, and Institutional Food Waste Management Strategies in the United States. AB - New regulations and targets limiting the disposal of food waste have been recently enacted in numerous jurisdictions. This analysis evaluated selected environmental implications of food waste management policies using life-cycle assessment. Scenarios were developed to evaluate management alternatives applicable to the waste discarded at facilities where food waste is a large component of the waste (e.g., restaurants, grocery stores, and food processors). Options considered include anaerobic digestion (AD), aerobic composting, waste-to energy combustion (WTE), and landfilling, and multiple performance levels were considered for each option. The global warming impact ranged from approximately 350 to -45 kg CO2e Mg(-1) of waste for scenarios using AD, -190 to 62 kg CO2e Mg( 1) for those using composting, -350 to -28 kg CO2e Mg(-1) when all waste was managed by WTE, and -260 to 260 kg CO2e Mg(-1) when all waste was landfilled. Landfill diversion was found to reduce emissions, and diverting food waste from WTE generally increased emissions. The analysis further found that when a 20 year GWP was used instead of a 100 year GWP, every scenario including WTE was preferable to every scenario including landfill. Jurisdictions seeking to enact food waste disposal regulations should consider regional factors and material properties before duplicating existing statutes. PMID- 27387289 TI - Safe and Effective Deployment of Personnel to Support the Ebola Response - West Africa. AB - From the initial task of getting "50 deployers within 30 days" into the field to support the 2014-2016 Ebola virus disease (Ebola) epidemic response in West Africa to maintaining well over 200 staff per day in the most affected countries (Guinea, Liberia, and Sierra Leone) during the peak of the response, ensuring the safe and effective deployment of international responders was an unprecedented accomplishment by CDC. Response experiences shared by CDC deployed staff returning from West Africa were quickly incorporated into lessons learned and resulted in new activities to better protect the health, safety, security, and resiliency of responding personnel. Enhanced screening of personnel to better match skill sets and experience with deployment needs was developed as a staffing strategy. The mandatory predeployment briefings were periodically updated with these lessons to ensure that staff were aware of what to expect before, during, and after their deployments. Medical clearance, security awareness, and resiliency programs became a standard part of both predeployment and postdeployment activities. Response experience also led to the identification and provision of more appropriate equipment for the environment. Supporting the social and emotional needs of deployed staff and their families also became an agency focus for care and communication. These enhancements set a precedent as a new standard for future CDC responses, regardless of size or complexity.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27387290 TI - Heterogeneous Circulating Angiogenic Cell Responses to Acute Maximal Exercise. AB - PURPOSE: Circulating angiogenic cells (CAC) comprise multiple subpopulations of exercise-inducible peripheral blood mononuclear cells (PBMC) that promote angiogenesis and maintain endothelial integrity. We examined the effect of acute maximal exercise on CD31, CD62E, CD14/CD31, CD34/VEGFR2, CD3/CD31, and CD3 PBMC in young, healthy adults. METHODS: Blood samples were collected before and immediately after a graded treadmill exercise test for CAC analysis via flow cytometry. RESULTS: Maximal exercised produced 40%, 29%, 33%, 14%, and 33% increases in lymphocytic CD31, monolymphocytic CD31, CD62E, CD14/CD31, and CD34/VEGFR2 PBMC, respectively (P < 0.05). CD3/CD31 and CD3 cells were not altered with exercise. CD62E and CD14/CD31 PBMC were selectively augmented in women by 54% and 20%, respectively (P < 0.05). Exploratory analyses indicated that maximal exercise induced greater increases in CD62E and CD14/CD31 PBMC among women in the luteal phase compared with those in the follicular phase (P < 0.05). Basal lymphocytic PBMC and postexercise lymphocytic and monolymphocytic CD31 PBMC were lower among contraceptive users than nonusers. CONCLUSIONS: Maximal exercise induces a robust CAC response encompassing both progenitor and nonprogenitor cell types, with these effects differing between men and women for CD62E and CD14/CD31 cell types and the potential influence of menstrual cycle phase and contraceptive use. PMID- 27387288 TI - Habenular Neurogenesis in Zebrafish Is Regulated by a Hedgehog, Pax6 Proneural Gene Cascade. AB - The habenulae are highly conserved nuclei in the dorsal diencephalon that connect the forebrain to the midbrain and hindbrain. These nuclei have been implicated in a broad variety of behaviours in humans, primates, rodents and zebrafish. Despite this, the molecular mechanisms that control the genesis and differentiation of neural progenitors in the habenulae remain relatively unknown. We have previously shown that, in zebrafish, the timing of habenular neurogenesis is left-right asymmetric and that in the absence of Nodal signalling this asymmetry is lost. Here, we show that habenular neurogenesis requires the homeobox transcription factor Pax6a and the redundant action of two proneural bHLH factors, Neurog1 and Neurod4. We present evidence that Hedgehog signalling is required for the expression of pax6a, which is in turn necessary for the expression of neurog1 and neurod4. Finally, we demonstrate by pharmacological inhibition that Hedgehog signalling is required continuously during habenular neurogenesis and by cell transplantation experiments that pathway activation is required cell autonomously. Our data sheds light on the mechanism underlying habenular development that may provide insights into how Nodal signalling imposes asymmetry on the timing of habenular neurogenesis. PMID- 27387291 TI - Frequency of Breaks in Sedentary Time and Postprandial Metabolic Responses. AB - PURPOSE: To compare the metabolic effects of breaking up sedentary time with prolonged periods of standing versus multiple shorter standing bouts with the same total duration to determine whether, in principle, altering the frequency of "standing breaks" in sedentary time, influences metabolic responses over the course of the day. METHODS: Ten normoglycemic overweight/obese men (age, 33 +/- 13 yr; body mass index, 28.3 +/- 3.0 kg.m; mean +/- SD) each participated in three experimental trials in random order, in which they arrived fasted, then consumed a test breakfast (8 kcal.kg body weight, with 37% energy from fat, 49% from carbohydrates, 14% from protein) and, 4 h later, an identical test lunch. Expired air and blood samples were taken fasted and for 8 h postprandially. In one trial (uninterrupted sitting), participants sat continuously throughout the observation period; in the prolonged standing (PRO-Stand) trial, participants stood still for 15 min every 30 min; and in the intermittent standing trial (INT Stand), they stood for 1.5 min, 10 times every 30 min. RESULTS: Compared with uninterrupted sitting, energy expenditure was 320 +/- 62 kJ (10.7% +/- 2.0%) higher in PRO-Stand and 617 +/- 76 kJ (20.4% +/- 2.3%) higher in INT-Stand: energy expenditure in INT-Stand was 296 +/- 78 kJ (9.0% +/- 2.3%) higher than PRO Stand (mean +/- SEM; all P < 0.001). However, there were no significant differences between trials in postprandial glucose, insulin, or triglyceride responses. CONCLUSIONS: These data demonstrate an independent effect of frequency of sedentary breaks on energy expenditure which provides an explanation for the association between frequency of sedentary breaks and adiposity observed in epidemiological data. However, it may be necessary to break up sitting with activities of greater intensity than quiet standing to positively influence glucose, insulin, and triglyceride metabolism in relatively young, normoglycemic, overweight/obese men. PMID- 27387292 TI - Footwear Matters: Influence of Footwear and Foot Strike on Load Rates during Running. AB - INTRODUCTION: Running with a forefoot strike (FFS) pattern has been suggested to reduce the risk of overuse running injuries, due to a reduced vertical load rate compared with rearfoot strike (RFS) running. However, resultant load rate has been reported to be similar between foot strikes when running in traditional shoes, leading to questions regarding the value of running with a FFS. The influence of minimal footwear on the resultant load rate has not been considered. This study aimed to compare component and resultant instantaneous loading rate (ILR) between runners with different foot strike patterns in their habitual footwear conditions. METHODS: Twenty-nine injury-free participants (22 men, seven women) ran at 3.13 m.s along a 30-m runway, with their habitual foot strike and footwear condition. Ground reaction force data were collected. Peak ILR values were compared between three conditions; those who habitually run with an RFS in standard shoes, with an FFS in standard shoes, and with an FFS in minimal shoes. RESULTS: Peak resultant, vertical, lateral, and medial ILR were lower (P < 0.001) when running in minimal shoes with an FFS than in standard shoes with either foot strike. When running with an FFS, peak posterior ILR were lower (P < 0.001) in minimal than standard shoes. CONCLUSIONS: When running in a standard shoe, peak resultant and component ILR were similar between footstrike patterns. However, load rates were lower when running in minimal shoes with a FFS, compared with running in standard shoes with either foot strike. Therefore, it appears that footwear alters the load rates during running, even with similar foot strike patterns. PMID- 27387294 TI - Neural Control of Posture in Individuals with Persisting Postconcussion Symptoms. AB - INTRODUCTION: Postural instability has been shown to characterize individuals who suffered from long-term symptoms after mild traumatic brain injury. However, recordings of neural processes during postural control are difficult to realize with standard neuroimaging techniques. Thus, we used functional nearinfrared spectroscopy to investigate brain oxygenation of individuals with persistent postconcussion symptoms (pPCS) during postural control in altered environments. METHODS: We compared brain oxygenation and postural sway during balance control in three groups: individuals suffering from pPCS, individuals with a history of mild traumatic brain injury but without pPCS, and healthy controls. Individuals were investigated during postural control tasks with six different conditions: i) eyes opened, ii) eyes closed, and iii) blurred visual input, each while standing a) on a stable and b) an unstable surface. RESULTS: In all groups, during the eyes closed/unstable surface condition as compared with the other conditions, the postural sway increased as well as the brain oxygenation in frontal brain cortices. In the most difficult balance condition, as compared with the other two groups, subjects with pPCS applied more force over time to keep balance as measured by the force plate system with a significantly greater activation in frontopolar/orbitofrontal areas of the right hemisphere. CONCLUSIONS: As subjects with pPCS applied more force over time to control balance, we propose that with regard to cognitive processes, the increase of cerebral activation in these individuals indicates an increase of attention-demanding processes during postural control in altered environments. PMID- 27387293 TI - Biological Maturation and Physical Activity in South Korean Adolescent Girls. AB - INTRODUCTION/PURPOSE: To examine whether body fatness (i.e., body mass index and percent body fat) and psychosocial correlates of physical activity (PA) mediate the relationships between pubertal status and PA and sedentary behavior (SB) among South Korean adolescent girls. METHODS: Pubertal status, body fatness, sport competence, perceived barriers to PA, self-efficacy, parental support for PA, self-reported and step-determined PA, and self-reported SB were assessed among 236 South Korean adolescent girls (mean age = 13.56 +/- 1.2 yr). RESULTS: A direct association was identified between pubertal status and PA in all models; more advanced pubertal status predicted lower PA among South Korean adolescents (b = -0.51 to -0.57; P < 0.001). Indirect effects on the pubertal status-PA relationship were also found: body fatness, perceived barriers to PA, and self efficacy mediated the relationship between pubertal status and PA. Parental support for PA did not moderate the relationship between maturation and PA. SB was not associated with pubertal status. CONCLUSIONS: This study found mediated effects of body fatness, and psychosocial correlates (i.e., perceived barriers to PA, self-efficacy) on the relationship between maturity and PA among South Korean adolescent girls. Efforts to promote PA among South Korean adolescent girls should focus on reducing perceived barriers to PA, and increasing self-efficacy by providing more opportunities to have positive, and enjoyable experiences in PA among early-maturing girls. PMID- 27387295 TI - Psychobiological Responses to Preferred and Prescribed Intensity Exercise in Major Depressive Disorder. AB - : Exercise acutely improves mood in major depressive disorder (MDD). However, it is unknown whether benefits differ depending on whether exercise intensity is self-selected or prescribed. PURPOSE: This study aimed to compare psychological and biological responses to preferred and prescribed steady-state exercise intensities to a patient-selected preferred intensity. METHOD: Female adults (N = 24, age = 38.6 +/- 14.0 yr) diagnosed with MDD completed four 30-min sessions of cycling exercise at three prescribed intensities (RPE of 11, 13, and 15) and one session with a self-selected intensity (preferred). Order was randomized and counterbalanced. Depressed mood (DM) was evaluated before, 10 min, and 30 min postexercise using the Profile of Mood States. Serum brain-derived neurotrophic factor (BDNF) was measured before and within 10 min postexercise. Changes in BDNF and DM for the preferred session were compared with the following prescribed sessions: 1) performed at the most similar intensity (matched on RPE; closest) and 2) with the greatest improvement in DM (greatest). RESULTS: Compared with the preferred session, improvement in DM was significantly larger after the greatest session (30 min postexercise: -11.8 +/- 7.4 vs -3.4 +/- 4.8), and the BDNF response was significantly greater after the closest session (5.4 +/- 6.9 vs -1.4 +/- 9.8 ng.mL). CONCLUSIONS: Permitting patients to select their own exercise intensity did not maximize improvements in mood. Further, preferred intensity exercise was also associated with a smaller BDNF response. Overall, the results suggest that exercise undertaken to improve mood should be prescribed on an individual basis in MDD and not necessarily based on the patient's preferred intensity. Clinicians, psychologists, and other practitioners should consider providing clear exercise intensity recommendations for symptom management in depression rather than allowing patients to self-select their intensity. PMID- 27387296 TI - Association between Consumption of Coffee and the Prevalence of Periodontitis: The 2008-2010 Korea National Health and Nutrition Examination Survey. AB - BACKGROUND: This study was performed to assess the relationship between the consumption of coffee and periodontitis using nationally representative data. METHODS: The data from the Korea National Health and Nutrition Examination Survey were used; the analysis in this study was confined to a total of 16,730 respondents over 19 years old who had no missing values for the consumption of coffee or outcome variables. A community periodontal index greater than or equal to code 3 was defined as periodontal disease. RESULTS: Consumption of coffee was significantly higher in the individuals with periodontitis in males. The odds ratios of the percentage of individuals with periodontitis tended to increase with the consumption of coffee. Adjusted odds ratios and their 95% confidence intervals of the male participants were 1, 1.131(0.792-1.617), 1.161(0.857 1.573), 1.053(0.805-1.379), 1.299(1.007-1.676), and 1.458(1.141-1.862) for once per month or less, once per month=60 years) with metastatic or advanced STS. A total of 120 patients will be randomized 1:2 to receive doxorubicin or pazopanib, stratified by Eastern Cooperative Oncology Group performance status (0-1 vs. 2) and liposarcoma histology (yes vs. no). The primary endpoint is progression-free survival based on local tumor assessment according to Response Evaluation Criteria in Solid Tumors criteria. Secondary endpoints include grade 4 neutropenia and febrile neutropenia in hierarchical order, as well as overall survival, objective response rate, health-related quality of life, and geriatric assessments. DISCUSSION: Pazopanib is associated with promising tolerability according to previous studies and may offer a significant clinical advantage in first-line treatment of STS compared with doxorubicin. The elderly population seems especially appealing for such an approach, since these patients are not suitable for aggressive combination therapy. The EPAZ study will confirm whether pazopanib may be an alternative to toxic chemotherapy for elderly patients with STS. TRIAL REGISTRATION: ClinicalTrials.gov NCT01861951 ; registered on 11 April 2013. EudraCT 2011-004168-30; registered on 4 June 2012. PMID- 27387326 TI - Navigating HIV prevention policy and Islam in Malaysia: contention, compatibility or reconciliation? Findings from in-depth interviews among key stakeholders. AB - BACKGROUND: Malaysia is a multicultural society, predominantly composed of a Muslim majority population, where Islam is influential. Malaysia has a concentrated HIV epidemic amongst high risk groups, such as, Intravenous Drug Users (IVDU), sex workers, transgender women and Men who have sex with Men (MSM). The objective of this study is to understand how Islam shapes HIV prevention strategies in Malaysia by interviewing the three key stakeholder groups identified as being influential, namely the Ministry of Health, Religious leaders and People living with HIV. METHODS: Thirty-Five in depth semi structured interviews were undertaken with religious leaders, Ministry of Health and People living with HIV in the last half of 2013 using purposive sampling. Interviews adhered to a topic guide, were audiotaped, and transcribed verbatim and analyzed using a framework analysis. RESULTS: Themes including the importance of Islam to health, stakeholder relationships and opinions on HIV prevention emerged. Islam was seen to play a pivotal role in shaping strategies relating to HIV prevention in Malaysia both directly and indirectly. Stakeholders often held different approaches to HIV prevention, which had to be sensitively considered, with some favouring promotion of Islamic principles, whilst others steering towards a more public health centred approach. CONCLUSIONS: The study suggests that Islam indeed plays an important role in shaping health policies and strategies related to HIV prevention in Malaysia. Certainly, stakeholders do hold differing viewpoints, such as stances of what constitutes the right approach to HIV prevention. However there are also areas of broad consensus, such as the importance in Islamic tradition to prevent harm and disease, which can be crafted into existing and future HIV prevention strategies in Malaysia, as well as the wider Muslim world. PMID- 27387327 TI - Serum HER2 extra-cellular domain, S100beta and CA 15-3 levels are independent prognostic factors in metastatic breast cancer patients. AB - BACKGROUND: Metastatic breast cancer (MBC) prognosis is highly variable, depending on various factors such as the biological subtype, the performance status, disease extension.... A better evaluation of a patient's prognostic factors could allow for a more accurate choice of treatments. The role of serum tumor markers remains, however, unclear in this population. Considering the recent interest in phenotypic changes and tumor heterogeneity during breast cancer progression, additional tumor markers could be interesting in this setting. METHODS: Two hundred fifty MBC patients treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples. The usual MBC clinical and pathological variables were collected, altogether with Cancer Antigen 15-3 (CA15-3), Carcinoembryonic Antigen (CEA), HER2 extra-cellular domain (ECD), Neuron Specific Enolase (NSE), S100beta protein and Matrix Metalloproteinase 9 (MMP-9) serum levels in order to determine their prognostic value. RESULTS: With a median follow-up of 40.8 months, median overall survival was 16.2 months (95 % CI 12.4 20.6). In multivariate analysis, the performance status, brain or subcutaneous metastases, the number of previous metastatic chemotherapy lines and the tumor biological subtype were independent prognostic factors. Elevated CA 15-3 (HR = 1.95, IC 95 % 1.31-2.93, p = 0.001), HER2 ECD (regardless of tumor HER2 status, HR = 2.51, IC 95 % 1.53-4.12, p < 0.001) and S100beta (HR = 1.93, IC 95 % 1.05 3.54, p = 0.033) serum levels were independently associated with a poor outcome. CONCLUSIONS: Serum CA 15-3, HER2 ECD and S100beta could represent useful independent prognostic factors in MBC. Of particular interest is the independent value of serum HER2 ECD levels, regardless of the tumor HER2 status, possibly linked to metastatic tumor heterogeneity. PMID- 27387329 TI - Nifedipine increases fetoplacental perfusion. AB - AIM: Our aim is to evaluate the effect of nifedipine on fetoplacental hemodynamic parameters. METHODS: A retrospective study was conducted at a tertiary center with 30 patients for whom nifedipine treatment was used as a tocolytic therapy for preterm labor. Initiation of this treatment was at 31.6+/-2.5 weeks of gestation. We combined the pulse Doppler imaging parameters with grayscale imaging via the Bernoulli theorem, which is called the "continuity equation", to get the fetoplacental perfusion (FPP). Evaluated parameters were the resistance index (RI), the pulsatility index (PI), systole/diastole ratios (S/D), the velocity-time integral of the umbilical artery (VTI), the radius of the umbilical artery, the peak systolic velocity and the mean pressure gradient in the umbilical artery. From these parameters, the FPP was acquired. RESULTS: We found that the RI, the PI and the S/D ratio did not change after treatment with nifedipine. The mean pressure gradient, the VTI and the peak systolic velocity increased after treatment with nifedipine. Nifedipine increases FPP from 166+/ 73.81 beat.cm3/min to 220+/-83.3 beat.cm3/min. DISCUSSION: Although nifedipine had no effect on the PI, the RI or the S/D, it increased the mean pressure gradient, the VTI and FPP. PMID- 27387328 TI - The role of social support on physical activity behaviour in adolescent girls: a systematic review and meta-analysis. AB - Adolescent girls have been targeted as a priority group for promoting physical activity levels however it is unclear how this can be achieved. There is some evidence to suggest that social support could impact the physical activity levels of adolescent girls, although the relationship is complex and not well understood. We aimed to systematically review and meta-analyse the relationship between social support and physical activity in adolescent girls, exploring how different types and providers of social support might influence the relationship. Articles were identified through a systematic search of the literature using 14 electronic databases, personal resources, grey literature, and reference lists of included studies and previous reviews. Search terms representing social support, physical activity and adolescent girls were identified and used in various combinations to form a search strategy which was adapted for different databases. Cross-sectional or longitudinal articles published in English that reported an association between social support and physical activity in adolescent girls between the ages of 10 to 19 years were included. Studies that focused only on clinical or overweight populations were excluded. Data extraction was carried out by one reviewer using an electronic extraction form. A random 25 % of included articles were selected for data extraction by a second reviewer to check fidelity. Risk of bias was assessed using a custom tool informed by the Critical Appraisal Skills Programme Cohort Study Checklist in conjunction with data extraction. Cross-sectional results were meta-analysed and longitudinal results were presented narratively. Small but significant associations between all available providers of total social support (except teachers) and physical activity were found (r = .14-.24). Small but significant associations were also identified for emotional, instrumental and modelling support for some providers of support (r = .10-.21). Longitudinal research supported the cross-sectional analyses. Many of the meta-analysis results suggested high heterogeneity and there was some evidence of publication bias, therefore, the meta-analysis results should be interpreted with caution. In conclusion, the meta-analysis results suggest that social support is not a strong predictor of physical activity in adolescent girls though parents and friends may have a role in enhancing PA. TRIAL REGISTRATION: PROSPERO 2014: CRD42014006738. PMID- 27387330 TI - Obstetric analgesia - update 2016. AB - Neuraxial labor analgesia can be initiated via combined spinal-epidural (CSE) or stand-alone epidural. Pros and cons of these techniques are outlined in this review. In recent years computer-integrated patient-controlled epidural analgesia (CI-PCEA) and programed intermittent epidural boluses (PIEB) have been developed, adding to continuous infusion and PCEA for the maintenance of neuraxial analgesia. Postdural puncture headache (PDPH) and fever can occur secondary to labor epidural that both have clinical relevance for the care givers. Insights into the mechanism of epidural fever and treatment strategies for PDPH are outlined. Due to the increase in obesity the specific considerations for this patient group are discussed. New data have been presented for remifentanil, an ultra-shortly acting opioid, that is used in obstetric analgesia. Without breaking new data, the use of nitrous oxide especially by midwives has a kind of renaissance, and this will be discussed, too. PMID- 27387331 TI - Tobacco smoke exposure induces irreversible alteration of testicular function in prepubertal rats. AB - BACKGROUND: Smoking is a serious public health problem and an important risk factor of many diseases. The present study evaluated whether or not the influence of prolonged tobacco smoke (TS) exposure on spermatic indices and reproductive hormones would be reversible in young and adult rats. METHODS: Prepubertal and adult rats were grouped into five (I, II, III, IV, and V) separately (n=5/group) and exposed to TS at target concentrations of 0, 0.5, 1.0, 0.5, and 1.0 mg nicotine/day, respectively for 30 days using the whole body exposure inhalation method. Groups I, II, and III were sacrificed 24 h after TS exposure, while groups IV and V were allowed to recover for 30 days before they were sacrificed. RESULTS: Sperm count and motility were significantly (p<0.05) reduced in exposed prepubertal and adult rats. Additionally, sperm morphology was unaltered, testosterone was reduced, while luteinizing hormone (LH) and follicle stimulating hormone (FSH) were elevated compared to the non-TS exposed control group. The reductions in sperm count and motility were reversed only in adult recovery rats. LH and FSH elevations were reversed in all recovery animals, but testosterone concentrations remained lower than control. Furthermore, malondialdehyde levels in testes of exposed rats were significantly increased. This was reversed only in adult recovery rats that received 0.5 mg nicotine. Testicular levels of catalase, reduced glutathione, and superoxide dismutase were unaltered, except in prepubertal rats wherein catalase was decreased in both treated and recovery groups. CONCLUSIONS: The TS exposure alters sperm characteristics reversibly in adult, but irreversibly in prepubertal rats, which is attributable to elevation of oxidative stress. PMID- 27387332 TI - A two site comparison of two point-of-care activated clotting time systems. PMID- 27387333 TI - Delayed onset porous polyethylene implant-related inflammation after orbital blowout fracture repair: four case reports. AB - BACKGROUND: Porous polyethylene implants are commonly used in orbital blowout fracture repair because of purported biocompatibility, durability, and low frequency of complications. Delayed inflammation related to porous polyethylene sheet implants is very rare and no case series of this condition have been reported. CASE PRESENTATION: This is a retrospective review of clinical presentations, radiographic findings, histopathological findings, treatments, and outcomes of patients who developed delayed complications in orbital blowout fracture repair using porous polyethylene sheets. Four male patients were included with a mean age of 49 years (range 35-69 years). Blowout fracture repair was complicated with implant-related inflammation 10 months, 2 years, 3 years, and 8 years after surgery. Chronic and subacute orbital inflammatory signs were noted in two patients and acute fulminant orbital inflammation was found in two patients. Three patients developed peri-implant abscesses and one patient had a soft tissue mass around the implant. All patients underwent implant removal and two of these patients with paranasal sinusitis had sinus surgery. Histopathological findings revealed chronic inflammatory changes with fibrosis, and one patient had foreign body granuloma with culture positive Staphylococcus aureus. CONCLUSIONS: Delayed complications with porous polyethylene sheets used in orbital blowout fracture repair may occur many years following the initial surgery in immunocompetent patients. Low-grade or fulminant inflammation could complicate blowout fracture repair related with the implant. PMID- 27387334 TI - Post-laparoscopic cholecystectomy Mirizzi syndrome induced by polymeric surgical clips: a case report and review of the literature. AB - BACKGROUND: Laparoscopic cholecystectomy is the gold standard treatment of gallbladder disease. Post-cholecystectomy syndrome is a severe postoperative complication which can be caused by multiple mechanisms and can present with multiple disorders. The wide use of laparoscopy induces the need to understand more clearly the presentation and pathophysiology of this syndrome. Post cholecystectomy Mirizzi syndrome is one form of this syndrome and, according to literature, this is the first report that clearly describes it. CASE PRESENTATION: We describe the case of a 62-year-old Greek woman who underwent laparoscopic cholecystectomy because of gallstone disease. A few days after surgery, post-cholecystectomy syndrome gradually developed with mild bilirubin increase in association with epigastric pain, nausea, and vomiting. After performing ultrasound, magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography, we conducted a second laparoscopic surgery to manage the obstruction, which was converted to open surgery because of the remaining inflammation from the post-endoscopic retrograde cholangiopancreatography acute pancreatitis. Four polymeric laparoscopic clips were removed because they were identified as the cause of her post cholecystectomy syndrome. She had a quick recovery without further complications. CONCLUSIONS: Postoperative Mirizzi syndrome induced by the migration of polymer laparoscopic clips is a rare (only one case referring to polymeric clips has been published in the literature) but a well-identified complication of laparoscopic cholecystectomy which can confuse the diagnostic and therapeutic field requiring simultaneous immediate management. PMID- 27387336 TI - Exposure to siRNA-GalNAc Conjugates in Systems of the Standard Test Battery for Genotoxicity. AB - Registration of pharmaceuticals requires an assessment of their genotoxic potential using in vitro and in vivo tests outlined in the International Conference on Harmonisation (ICH) guidance S2(R1). We have evaluated numerous siRNA-N-acetylgalactosamine (GalNAc) conjugates containing phosphorothioate linkages and various combinations of 2'-fluoro and 2'-O-methyl ribose modifications of multiple nucleotides in the ICH battery of assays, all of which have uniformly yielded negative results. To verify these negative genotoxicity results, in this study we confirm test article exposure using toolkit small interfering RNAs (siRNAs) representative of those in the clinic. In the Ames test, the highest uptake of the siRNA-GalNAc conjugates occurred at 1 h postdose in all bacterial strains independent of siRNA sequence or chemistry (up to ~14,000 siRNA molecules per cell), followed by metabolic degradation of the parent siRNA at 6, 24, and 48 h postdose. siRNA-GalNAc conjugates were internalized by bacteria as assessed by protection from the addition of nucleases to the culture media following uptake and by the requirement of cell lysis for detection of the siRNA. In the in vitro chromosome aberration assay, uptake was observed in Chinese hamster ovary cells (up to ~5,500 siRNA molecules per cell at 21 h postdose) and in CD3+ human peripheral blood lymphocytes (up to ~500 siRNA molecules per cell at 21 h postdose). In the in vivo micronucleus assay in rat bone marrow, exposure to parent siRNA was 100-350 MUg of antisense strand per gram of protein at 24 and 48 h postlimit dose of 2 g/kg. Loss of terminal nucleotides was detected in bone marrow by mass spectrometry, indicating exposure to monomer metabolites as well. Negative genotoxicity results were also confirmed in an in vitro double-strand DNA break assay in HeLa and HepG2 cells where exposure was maximized using transfection reagents. Thus negative genotoxicity assay results for siRNA-GalNAc conjugates were valid and not the result of poor or no intracellular exposure. PMID- 27387337 TI - Phylogenetic Variants of Rickettsia africae, and Incidental Identification of "Candidatus Rickettsia Moyalensis" in Kenya. AB - BACKGROUND: Rickettsia africae, the etiological agent of African tick bite fever, is widely distributed in sub-Saharan Africa. Contrary to reports of its homogeneity, a localized study in Asembo, Kenya recently reported high genetic diversity. The present study aims to elucidate the extent of this heterogeneity by examining archived Rickettsia africae DNA samples collected from different eco regions of Kenya. METHODS: To evaluate their phylogenetic relationships, archived genomic DNA obtained from 57 ticks a priori identified to contain R. africae by comparison to ompA, ompB and gltA genes was used to amplify five rickettsial genes i.e. gltA, ompA, ompB, 17kDa and sca4. The resulting amplicons were sequenced. Translated amino acid alignments were used to guide the nucleotide alignments. Single gene and concatenated alignments were used to infer phylogenetic relationships. RESULTS: Out of the 57 DNA samples, three were determined to be R. aeschlimanii and not R. africae. One sample turned out to be a novel rickettsiae and an interim name of "Candidatus Rickettsia moyalensis" is proposed. The bonafide R. africae formed two distinct clades. Clade I contained 9% of the samples and branched with the validated R. africae str ESF-5, while clade II (two samples) formed a distinct sub-lineage. CONCLUSIONS: This data supports the use of multiple genes for phylogenetic inferences. It is determined that, despite its recent emergence, the R. africae lineage is diverse. This data also provides evidence of a novel Rickettsia species, Candidatus Rickettsia moyalensis. PMID- 27387338 TI - Near-Surface and Bulk Behavior of Bicontinuous Microemulsions under High-Pressure Conditions. AB - The effect of hydrostatic pressure on the structure of a bicontinuous microemulsion in the presence of a solid interface has been studied by X-ray reflectometry and compared to the bulk behavior determined by small-angle X-ray scattering. Surface-induced lamellar ordering is observed close to the hydrophilic interface, which persists upon compression. The lamellar domains are compressed, but the correlation length of lamellar order does not change with pressure. SAXS measurements on the bulk microemulsion revealed an increased order upon pressurization. Although pressure can cause the formation of highly ordered lamellar phases from ordered bicontinuous cubic phases, such a scenario is not observed for the disordered analogue studied here. High pressure increases the stiffness of the interfacial surfactant layer, but this is not sufficient to overcome the loss in conformational entropy that would result from a transition to an ordered lamellar phase. Possible technological and biological implications of our results are briefly discussed. PMID- 27387335 TI - The emerging role of gasotransmitters in the pathogenesis of tuberculosis. AB - Mycobacterium tuberculosis (Mtb) is a facultative intracellular pathogen and the second largest contributor to global mortality caused by an infectious agent after HIV. In infected host cells, Mtb is faced with a harsh intracellular environment including hypoxia and the release of nitric oxide (NO) and carbon monoxide (CO) by immune cells. Hypoxia, NO and CO induce a state of in vitro dormancy where Mtb senses these gases via the DosS and DosT heme sensor kinase proteins, which in turn induce a set of ~47 genes, known as the Mtb Dos dormancy regulon. On the contrary, both iNOS and HO-1, which produce NO and CO, respectively, have been shown to be important against mycobacterial disease progression. In this review, we discuss the impact of O2, NO and CO on Mtb physiology and in host responses to Mtb infection as well as the potential role of another major endogenous gas, hydrogen sulfide (H2S), in Mtb pathogenesis. PMID- 27387339 TI - A set of mini-Mu transposons for versatile cloning of circular DNA and novel dual transposon strategy for increased efficiency. AB - Mu transposition-based cloning of DNA circles employs in vitro transposition reaction to deliver both the plasmid origin of replication and a selectable marker into the target DNA of interest. We report here the construction of a platform for the purpose that contains ten mini-Mu transposons with five different replication origins, enabling a variety of research approaches for the discovery and study of circular DNA. We also demonstrate that the simultaneous use of two transposons, one with the origin of replication and the other with selectable marker, is beneficial as it improves the cloning efficiency by reducing the fraction of autointegration-derived plasmid clones. The constructed transposons now provide a set of new tools for the studies on DNA circles and widen the applicability of Mu transposition based approaches to clone circular DNA from various sources. PMID- 27387340 TI - Erratum to: The Role of Sirtuins in Cartilage Homeostasis and Osteoarthritis. PMID- 27387341 TI - Intense focal pituitary FDG uptake due to intravascular large B-cell lymphoma in pyrexia of unknown origin. PMID- 27387343 TI - Climate Change and Health in the Urban Context: The Experience of Barcelona. AB - Climate change poses huge challenges for public health, and cities are at the forefront of this process. The purpose of this paper is to present the issues climate change poses for public health in the city of Barcelona, how they are being addressed, and what are the current major challenges, trying to contribute to the development of a baseline understanding of the status of adaptation in cities from a public health perspective. The major issues related to climate change faced by the city are common to other urban centers in a Mediterranean climate: heat waves, water availability and quality, air quality, and diseases transmitted by vectors, and all are reviewed in detail with empirical data. They are not a potential threat for the future, but have actually challenged the city services and infrastructure over the last years, requiring sustainable responses and rigorous planning. PMID- 27387342 TI - Association between the docosahexaenoic acid to arachidonic acid ratio and acute coronary syndrome: a multicenter observational study. AB - BACKGROUND: A low eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio is a known risk for acute coronary syndrome (ACS). However, the association between the docosahexaenoic acid (DHA) to AA ratio and ACS remains unclear. This study aimed to assess the association between the DHA/AA ratio and ACS by patient characteristics. METHODS: We enrolled 1733 patients and evaluated the serum levels of polyunsaturated fatty acids in 5 cardiology departments in a metropolitan area of Japan. We assessed the relationship between the DHA/AA ratio (median cut-off value: 0.903) and ACS according to the following 10 subgroups: sex, age, diabetes mellitus, hypertension, dyslipidemia, smoking history, family history of ischemic heart disease, chronic kidney disease, obesity, and history of coronary revascularization. RESULTS: Interaction tests in the 10 subgroup analyses revealed a significant difference for adjusted log odds ratios between male and females (p = 0.01), and those with and without hypertension (p = 0.06). Especially in the subgroup based on sex difference, a high DHA/AA ratio was significantly associated with a low risk of ACS among men (adjusted odds ratio = 0.389; 95 % confidence interval: 0.211-0.716). In contrast, a reverse association was found among women, although this was not statistically significant (adjusted odds ratio = 3.820; 95 % confidence interval: 0.718-20.325). CONCLUSIONS: The association between the DHA/AA ratio and ACS differed by clinical characteristic. Notably, patients with a low DHA/AA ratio had a higher risk of ACS than those with a high DHA/AA ratio, and this was significant for men in particular. PMID- 27387344 TI - Macrophage phenotypic subtypes diametrically regulate epithelial-mesenchymal plasticity in breast cancer cells. AB - BACKGROUND: Metastatic progression of breast cancer involves phenotypic plasticity of the carcinoma cells moving between epithelial and mesenchymal behaviors. During metastatic seeding and dormancy, even highly aggressive carcinoma cells take on an E-cadherin-positive epithelial phenotype that is absent from the emergent, lethal metastatic outgrowths. These phenotypes are linked to the metastatic microenvironment, though the specific cells and induction signals are still to be deciphered. Recent evidence suggests that macrophages impact tumor progression, and may alter the balance between cancer cell EMT and MErT in the metastatic microenvironment. METHODS: Here we explore the role of M1/M2 macrophages in epithelial-mesenchymal plasticity of breast cancer cells by coculturing epithelial and mesenchymal cells lines with macrophages. RESULTS: We found that after polarizing the THP-1 human monocyte cell line, the M1 and M2-types were stable and maintained when co-cultured with breast cancer cells. Surprisingly, M2 macrophages may conferred a growth advantage to the epithelial MCF-7 cells, with these cells being driven to a partial mesenchymal phenotypic as indicated by spindle morphology. Notably, E cadherin protein expression is significantly decreased in MCF-7 cells co-cultured with M2 macrophages. M0 and M1 macrophages had no effect on the MCF-7 epithelial phenotype. However, the M1 macrophages impacted the highly aggressive mesenchymal like MDA-MB-231 breast cancer cells to take on a quiescent, epithelial phenotype with re-expression of E-cadherin. The M2 macrophages if anything exacerbated the mesenchymal phenotype of the MDA-MB-231 cells. CONCLUSION: Our findings demonstrate M2 macrophages might impart outgrowth and M1 macrophages may contribute to dormancy behaviors in metastatic breast cancer cells. Thus EMT and MErT are regulated by selected macrophage phenotype in the liver metastatic microenvironment. These results indicate macrophage could be a potential therapeutic target for limiting death due to malignant metastases in breast cancer. PMID- 27387345 TI - Level of Discomfort Decreases After the Administration of Continuous Palliative Sedation: A Prospective Multicenter Study in Hospices and Palliative Care Units. AB - CONTEXT: A gold standard or validated tool for monitoring the level of discomfort during continuous palliative sedation (CPS) is lacking. Therefore, little is known about the course of discomfort in sedated patients, the efficacy of CPS, and the determinants of discomfort during CPS. OBJECTIVES: To identify the course of discomfort in patients receiving CPS. METHODS: A prospective observational multicenter study in nine hospices and palliative care units was performed. The Discomfort Scale-Dementia of Alzheimer Type (DS-DAT) was independently assessed for monitoring of patient discomfort during CPS. The DS-DAT scores range from 0 (no observed discomfort) to a maximum of 27 (high level of observed discomfort). Using a mixed model, the mean group score of discomfort between four predefined time frames of CPS was compared, correcting for confounding patient characteristics. RESULTS: A total of 130 patients were sedated, and the DS-DAT was completed in 106 patients at least once. The median duration of the sedation in these 106 patients was 25.5 hours (range 2-161). The mean score of the DS-DAT in the phase before sedation was 12.16 (95% CI 9.83-14.50) and decreased significantly to 8.06 (95% CI 5.53-10.58) in the titration phase of sedation. The mean score of the DS-DAT in the final phase of sedation was 7.42 (95% CI 4.90 9.94). CONCLUSION: This study shows that CPS is associated with a decrease in the level of discomfort within an acceptable time frame, although in some sedated patients higher levels of discomfort in the last hours of life occurred. Although the DS-DAT seems to be of value for monitoring the level of discomfort during CPS, the results of this study should be interpreted within the constraints of the limitations, and further research on the psychometric properties of this tool is needed before the DS-DAT can be used in clinical practice. PMID- 27387346 TI - Prospective Validation of the Objective Prognostic Score for Advanced Cancer Patients in Diverse Palliative Settings. AB - CONTEXT: Prognostication is an essential part of palliative care to aid decision making and negotiate goals of care. The Objective Prognostic Score (OPS) is an easy-to-use prognosticating tool to predict survival among far-advanced cancer patients in palliative care units (PCUs) in Korea. OBJECTIVES: This study aimed to prospectively validate the OPS for advanced cancer patients in the palliative care teams (PCTs), PCUs, and home-based palliative care (HPC) in Japan. METHODS: This was a substudy of a multicenter prospective cohort study that was conducted to validate and compare prognostic tools among advanced cancer patients in Japan. Participants' survival was calculated according to OPS 3 as a cutoff for predicting survival of less than three weeks. Overall accuracy and area under the receiver operator characteristic curves of OPS 3 were calculated for PCT, PCU, and HPC, respectively. RESULTS: A total of 1146 cases (PCTs 441, PCUs 519, and HPCs 186 cases) were included in final analyses. The overall accuracy of OPS 3 for predicting three-week survival ranged from 0.70 to 0.78 across diverse palliative care settings. The c-statistics ranged from 0.742 to 0.808 across three settings. Participants in the PCT showed the highest overall accuracy and c statistics for OPS. CONCLUSION: The OPS can be used for prognostication among advanced cancer patients in PCT, PCU, and HPC settings. PMID- 27387347 TI - Sustained activation of mTORC1 in macrophages increases AMPKalpha-dependent autophagy to maintain cellular homeostasis. AB - BACKGROUND: The mechanistic target of rapamycin complex 1 (mTORC1) is a well conserved serine/threonine protein kinase that controls autophagy as well as many other processes such as protein synthesis, cell growth, and metabolism. The activity of mTORC1 is stringently and negatively controlled by the tuberous sclerosis proteins 1 and 2 complex (TSC1/2). RESULTS: In contrast to the previous studies using Tsc1 knockout mouse embryonic fibroblasts (MEF) cells, we demonstrated evidence that TSC1 deficient macrophages exhibited enhanced basal and mycobacterial infection-induced autophagy via AMPKalpha-dependent phosphorylation of ULK1 (Ser555). These effects were concomitant with constitutive activation of mTORC1 and can be reversed by addition of amino acids or rapamycin, and by the knockdown of the regulatory-associated protein of mTOR, Raptor. In addition, increased autophagy in TSC1 deficient macrophages resulted in suppression of inflammation during mycobacterial infection, which was reversed upon amino acid treatment of the TSC1 deficient macrophages. We further demonstrated that TSC1 conditional knockout mice infected with Mycobacterium tuberculosis, the causative agent of tuberculosis, resulted in less bacterial burden and a comparable level of inflammation when compared to wild type mice. CONCLUSIONS: Our data revealed that sustained activation of mTORC1 due to defects in TSC1 promotes AMPKalpha-dependent autophagic flux to maintain cellular homeostasis. PMID- 27387348 TI - Tetramethylpyrazine-2'-O-sodium ferulate attenuates blood-brain barrier disruption and brain oedema after cerebral ischemia/reperfusion. AB - Disruption of blood-brain barrier (BBB) and subsequent oedema are major causes of the pathogenesis in ischaemic stroke with which the current clinical therapy remains unsatisfied. In this study, we examined the therapeutic effect of tetramethylpyrazine-2'-O-sodium ferulate (TSF)-a novel analogue of tetramethylpyrazine in alleviating BBB breakdown and brain oedema after cerebral ischaemia/reperfusion (I/R). Then, we explored the potential mechanism of the protection on BBB disruption in cerebral I/R rat models. Male Sprague-Dawley rats (250-300 g) were subjected to 120 min middle cerebral artery occlusion (MCAO), followed by 48 h reperfusion. TSF (10.8, 18 and 30 mg kg-1) and ozagrel (18 mg kg 1) were administrated by intravenous injection immediately for the first time and then received the same dose every 24 h for 2 days. We found that TSF treatment significantly attenuated the cerebral water content, infarction volume and improved neurological outcomes in MCAO rats compared to I/R models. Moreover, we investigated the effect of TSF on the BBB for that cerebral oedema is closely related to the permeability of the BBB. We found that the permeability of BBB was improved significantly in TSF groups compared to I/R model group by Evans blue leakage testing. Furthermore, the expressions of tight junction (TJ) proteins junction adhesion molecule-1 and occludin significantly decreased, but the protein expression of matrix metalloproteinase-9 (MMP-9) and aquaporin 4 (AQP4) increased after cerebral I/R, all of which were alleviated by TSF treatment. In conclusion, TSF significantly reduced BBB permeability and brain oedema, which were correlated with regulating the expression of TJ proteins, MMP-9 and AQP4. These findings provide a novel approach to the treatment of ischaemic stroke. PMID- 27387349 TI - Effectiveness of the sequential organ failure assessment, acute physiology and chronic health evaluation II, and simplified acute physiology score II prognostic scoring systems in paraquat-poisoned patients in the intensive care unit. AB - OBJECTIVE: This study was conducted to assess the ability of the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) II scoring systems, as well as the simplified acute physiology score (SAPS) II method to predict group mortality in intensive care unit (ICU) patients who were poisoned with paraquat. This will assist physicians with risk stratification. MATERIAL AND METHODS: The medical records of 244 paraquat poisoned patients admitted to the ICU from January 2010 to April 2015 were examined retrospectively. The SOFA, APACHE II, and SAPS II scores were calculated based on initial laboratory data in the emergency department and during the first 24 h of ICU admission. The probability of death was calculated for each patient based on the SOFA score, APACHE II score, and SAPS II. The ability of the SOFA score, APACHE II score, and SAPS II method to predict group mortality was assessed using a receiver operating characteristic (ROC) curve and calibration analyses. RESULTS: A total of 219 patients (mean age, 63 years) were enrolled. Sensitivities, specificities, and accuracies were 58.5%, 86.1%, and 64.0% for the SOFA, respectively; 75.1%, 86.1%, and 77.6% for the APACHE II scoring systems, respectively; and 76.1%, 79.1%, and 76.7% for the SAPS II, respectively. The areas under the curve in the ROC curve analysis for the SOFA score, APACHE II scoring system, and SAPS II were 0.716, 0.850, and 0.835, respectively. CONCLUSION: The SOFA, APACHE II, and SAPS II had different capabilities to discriminate and estimate early in-hospital mortality of paraquat-poisoned patients. Our results show that although the SOFA and SAPS II are easier and more quickly calculated than APACHE II, the APACHE II is superior for predicting mortality. We recommend use of the APACHE II for outcome predictions and risk stratification in paraquat-poisoned patients in the ICU. PMID- 27387350 TI - Comment on 'The effects of frequency lowering on speech perception in noise with adult hearing-aid users'. PMID- 27387351 TI - Duloxetine and Subacute Pain after Knee Arthroplasty when Added to a Multimodal Analgesic Regimen: A Randomized, Placebo-controlled, Triple-blinded Trial. AB - BACKGROUND: Duloxetine is effective for chronic musculoskeletal and neuropathic pain, but there are insufficient data to recommend the use of antidepressants for postoperative pain. The authors hypothesized that administration of duloxetine for 15 days would reduce pain with ambulation at 2 weeks after total knee arthroplasty. METHODS: In this triple-blinded, randomized, placebo-controlled trial, patients received either duloxetine or placebo for 15 days, starting from the day of surgery. Patients also received a comprehensive multimodal analgesic regimen including neuraxial anesthesia, epidural analgesia, an adductor canal block, meloxicam, and oxycodone/acetaminophen as needed. The primary outcome was the pain score (0 to 10 numeric rating scale) with ambulation on postoperative day 14. RESULTS: One hundred six patients were randomized and analyzed. On day 14, duloxetine had no effect on pain with ambulation; mean pain was 3.8 (SD, 2.3) for placebo versus 3.5 (SD, 2.1) for duloxetine (difference in means [95% CI], 0.4 [-0.5 to 1.2]; P = 0.386). Symptoms potentially attributable to duloxetine discontinuation at study drug completion (nausea, anxiety) occurred among nine patients (duloxetine) and five patients (placebo); this was not statistically significant (P = 0.247). Statistically significant secondary outcomes included opioid consumption (difference in mean milligram oral morphine equivalents [95% CI], 8.7 [3.3 to 14.1], P = 0.002 by generalized estimating equation) over the postoperative period and nausea on day 1 (P = 0.040). There was no difference in other side effects or in anxiety and depression scores. CONCLUSIONS: When included as a part of a multimodal analgesic regimen for knee arthroplasty, duloxetine does not reduce subacute pain with ambulation. PMID- 27387352 TI - Duloxetine for Subacute Pain Management after Total Knee Arthroplasty: Should We Write It Off or Reevaluate? PMID- 27387353 TI - Microglial Inhibition Influences XCL1/XCR1 Expression and Causes Analgesic Effects in a Mouse Model of Diabetic Neuropathy. AB - BACKGROUND: Recent studies indicated the involvement of some chemokines in the development of diabetic neuropathy; however, participation of the chemokine-C motif ligand (XCL) subfamily remains unknown. The goal of this study was to examine how microglial inhibition by minocycline hydrochloride (MC) influences chemokine-C-motif ligand 1 (XCL1)-chemokine-C-motif receptor 1 (XCR1)/G protein coupled receptor 5 expression and the development of allodynia/hyperalgesia in streptozotocin-induced diabetic neuropathy. METHODS: The studies were performed on streptozotocin (200 mg/kg, intraperitoneally)-induced mouse diabetic neuropathic pain model and primary glial cell cultures. The MC (30 mg/kg, intraperitoneally) was injected two times daily until day 21. XCL1 and its neutralizing antibody were injected intrathecally, and behavior was evaluated with von Frey and cold plate tests. Quantitative analysis of protein expression of glial markers, XCL1, and/or XCR1 was performed by Western blot and visualized by immunofluorescence. RESULTS: MC treatment diminished allodynia (0.9 +/- 0.1 g; n = 7 vs. 3.8 +/- 0.7 g; n = 7) and hyperalgesia (6.5 +/- 0.6 s; n = 7 vs. 16.5 +/- 1 s; n = 7) in the streptozotocin-induced diabetes. Repeated MC administration prevented microglial activation and inhibited the up-regulation of the XCL1/XCR1 levels. XCL1 administration (10 to 500 ng/5 MUl; n = 9) in naive mice enhanced nociceptive transmission, and injections of neutralizing XCL1 (4 to 8 MUg/5 MUl; n = 10) antibody into the mice with diabetic neuropathic pain diminished allodynia/hyperalgesia. Microglia activation evoked in primary microglial cell cultures resulted in enhanced XCL1 release and XCR1 expression. Additionally, double immunofluorescence indicated the widespread coexpression of XCR1-expressing cells with spinal neurons. CONCLUSIONS: In diabetic neuropathy, declining levels of XCL1 evoked by microglia inhibition result in the cause of analgesia. The putative mechanism corroborating this finding can be related to lower spinal expression of XCR1 together with the lack of stimulation of these XCR1 receptors, which are localized on neurons. PMID- 27387354 TI - Enhancement of Nitrite Reduction Kinetics on Electrospun Pd-Carbon Nanomaterial Catalysts for Water Purification. AB - We report a facile synthesis method for carbon nanofiber (CNF) supported Pd catalysts via one-pot electrospinning and their application for nitrite hydrogenation. A mixture of Pd acetylacetonate (Pd(acac)2), polyacrylonitrile (PAN), and nonfunctionalized multiwalled carbon nanotubes (MWCNTs) was electrospun and thermally treated to produce Pd/CNF-MWCNT catalysts. The addition of MWCNTs with a mass loading of 1.0-2.5 wt % (to PAN) significantly improved nitrite reduction activity compared to the catalyst without MWCNT addition. The results of CO chemisorption confirmed that the addition of MWCNTs increased Pd exposure on CNFs and hence improved catalytic activity. PMID- 27387355 TI - 6-Oxooxazolidine-quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR. AB - Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFR(T790M) and EGFR(L858R) kinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants. PMID- 27387356 TI - Synthesis and potent antiprotozoal activity of mono/di amidino 2 anilinobenzimidazoles versus Plasmodium falciparum and Trypanosoma brucei rhodesiense. AB - A series of mono and dicationic new 2-anilinobenzimidazole carboxamidines were prepared in a four step process starting from 4-amino-3-nitrobenzonitrile and corresponding o-phenylenediamines. Their antiparasitic activity against Plasmodium falciparum (P. falciparum) and Trypanosoma brucei rhodesiense (T.b. rhodesiense) were evaluated in vitro. Some of the dicationic compounds (10,12,14) showed equal or very close activity against T.b. rhodesiense with melarsoprol and also showed promising activity against P. falciparum as compared to chloroquine. Among the monocationic derivatives compound 21 exhibited best inhibitory activity against P. falciparum. PMID- 27387357 TI - Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted C(alpha) amino acids. AB - Eleven antimicrobial peptides (AMP) based on the incorporation of cyclic tetra substituted C(alpha) amino acids, as well as other unnatural amino acids were designed, synthesized and screened for in vitro activity against 18 strains of bacteria as well as 12 cancer cell lines. The AMPs discussed herein are derived from the following peptide sequence: Ac-GF(X)G(X)B(X)G(X)F(X)G(X)GB(X)BBBB-amide, X=any one of the following residues, A5c, A6c, Tic or Oic and B=any one of the following residues, Arg, Lys, Orn, Dpr or Dab. A diversity of in vitro inhibitory activity was observed for these AMPs. Several analogs exhibited single digit MUM activity against drug resistant bacteria including; multiple drug resistant Mycobacterium tuberculosis, extremely drug resistant Mycobacterium tuberculosis and MRSA. The physicochemical properties of the basic amino acid residues incorporated into these AMPs seem to play a major role in defining antibacterial activity. Overall hydrophobicity seems to play a limited role in defining antibacterial activity. The ESKAPE pathogens were used to compare the activity of these AMPs to another family of synthetic AMPs incorporating the unnatural amino acids Tic and Oic. In most cases similarly substituted members of both families exhibited similar inhibitory activity against the ESKAPE pathogens. In specific cases differences in activity as high as 15 fold were observed between analogs. In addition four of these AMPs exhibited promising IC50 (<7.5MUM) values against 12 different and diverse cancer cell lines. Five other AMPs exhibited promising IC50 (<7.5MUM) values against selected cancer cell lines. PMID- 27387358 TI - Short versus long-segment posterior fixation in the treatment of thoracolumbar junction fractures: a comparison of outcomes. AB - PURPOSE: To compare clinical and radiological outcomes between short (SSPF) and long-segment (LSPF) posterior fixation for thoracolumbar junction (TLJ) fractures. MATERIALS AND METHODS: Retrospective review of adult patients, with single-level, TLJ (T11-L2) fractures, treated with posterior fixation between 2007 and 2014 at a regional spinal centre. SSPF and LSPF were defined as transpedicular screw fixation at one and two levels above and below the fractured vertebra, respectively. Construct failure was defined as instrument breakage or screw pull-out requiring operative intervention. Two independent assessors measured the kyphotic Cobb angle at up to six months. RESULTS: A total of 28 patients were included with a median age of 38 years (range 20-76 years) and median follow-up period of 14 months (4-41 months). All patients sustained traumatic fractures and the male to female ratio was 19:9. AO fracture classes were: A (29%), B (50%) and C (21%). SSPF and LSPF were performed in 17 (61%) and 11 (39%) patients, respectively. There was no significant difference in age (Fisher's exact, p > 0.99), AO fracture class (chi-squared, p = 0.510), preop TLICS score (independent t-test, p = 0.668) and length of stay (independent t test, p = 0.106) between the groups. Construct failure occurred in three SSPF cases (3-14 months postop) and was associated with an increased mean loss of correction. By six months, the Cobb angle had increased significantly in the SSPF group (paired t-test, p = 0.049), but not the LSPF group (paired t-test, p = 0.157). CONCLUSIONS: Our data identified a trend towards better clinical and radiological outcomes in the LSPF, compared to the SSPF group. Although supported by some studies, these findings should be evaluated in future clinical trials. PMID- 27387359 TI - Synthesis of Nonequilibrium Supramolecular Peptide Polymers on a Microfluidic Platform. AB - The self-assembly of peptides and peptide mimetics into supramolecular polymers has been established in recent years as a route to biocompatible nanomaterials with novel mechanical, optical, and electronic properties. The morphologies of the resulting polymers are usually dictated by the strengths as well as lifetimes of the noncovalent bonds that lead to the formation of the structures. Together with an often incomplete understanding of the assembly mechanisms, these factors limit the control over the formation of polymers with tailored structures. Here, we have developed a microfluidic flow reactor to measure growth rates directly and accurately on the axial and radial faces of crystalline peptide supramolecular polymers. We show that the structures grow through two-dimensional nucleation mechanisms, with rates that depend exponentially on the concentration of soluble peptide. Using these mechanistic insights into the growth behavior of the axial and radial faces, we have been able to tune the aspect ratio of populations of dipeptide assemblies. These results demonstrate a general strategy to control kinetically self-assembly beyond thermodynamic products governed by the intrinsic properties of the building blocks in order to attain the required morphology and function. PMID- 27387360 TI - A position paper on drug allergy - pinpointing problems rather than suggesting solutions. PMID- 27387361 TI - Corrigendum. PMID- 27387362 TI - How open science helps researchers succeed. AB - Open access, open data, open source and other open scholarship practices are growing in popularity and necessity. However, widespread adoption of these practices has not yet been achieved. One reason is that researchers are uncertain about how sharing their work will affect their careers. We review literature demonstrating that open research is associated with increases in citations, media attention, potential collaborators, job opportunities and funding opportunities. These findings are evidence that open research practices bring significant benefits to researchers relative to more traditional closed practices. PMID- 27387363 TI - In vitro effects of simultaneous exposure to platinum and cadmium on the activity of antioxidant enzymes and DNA damage and potential protective effects of selenium and zinc. AB - Circulating platinum (Pt) is detectable in the blood of Pt-treated cancer patients for over a decade after the treatment. Prolonged exposure to Pt, in combination with adverse compounds from nutrition and lifestyle, such as cadmium (Cd), could increase the risk from second cancers. The aim of this study was to investigate the effects of simultaneous exposure to Cd- and Pt-compounds on oxidative and DNA damage and the possible protective effects of zinc (Zn) and selenium (Se). The aqueous solutions of PtCl4, CdCl2 * H2O, ZnCl2 and Na2SeO3 were added, alone or in combination, to whole blood and isolated erythrocytes to produce the final concentrations of 2000 MUg/L of Pt, 8 MUg/L of Cd, 100 MUg/L of Se, and 1000 MUg/L of Zn. The activity of copper, zinc-superoxide dismutase, glutathione peroxidase and glutathione in whole blood was determined after 1 h exposure in in vitro conditions. The induction of DNA strand-breaks in human peripheral blood leukocytes was determined with the alkaline comet assay after 24 h exposure. Exposure to Pt and/or Cd decreased the activities of antioxidant enzymes and elevated DNA damage compared to control. A statistically significant change in the activity of both enzymes and in the induction of DNA strand-breaks was observed in the cells treated with Pt + Cd combination, while the addition of Se and/or Zn resulted in partial recovery of these effects. The results indicate that combined exposure to Pt and Cd could disrupt antioxidant protection of the organism and increase DNA damage, whereas Se and Zn could partially ameliorate these harmful effects. PMID- 27387364 TI - Statistically Consistent k-mer Methods for Phylogenetic Tree Reconstruction. AB - Frequencies of k-mers in sequences are sometimes used as a basis for inferring phylogenetic trees without first obtaining a multiple sequence alignment. We show that a standard approach of using the squared Euclidean distance between k-mer vectors to approximate a tree metric can be statistically inconsistent. To remedy this, we derive model-based distance corrections for orthologous sequences without gaps, which lead to consistent tree inference. The identifiability of model parameters from k-mer frequencies is also studied. Finally, we report simulations showing that the corrected distance outperforms many other k-mer methods, even when sequences are generated with an insertion and deletion process. These results have implications for multiple sequence alignment as well since k-mer methods are usually the first step in constructing a guide tree for such algorithms. PMID- 27387365 TI - [From BNP to ST2: Which biomarkers to use in practice?] AB - The management of heart failure requires reproducible and easily accessible biomarkers. For diagnosis, measurement of natriuretic peptides is highly recommended as first line. For the stratification of patients, natriuretic peptide testing is highly recommended and other biomarkers such as troponin or fibrosis markers can also be used. For any biomarkers, changes in blood levels over time is more relevant than a single assay. For monitoring as well as guiding heart failure treatment, serial testing of natriuretic peptides is useful in young patients with systolic dysfunction. For the screening of high-risk patients, natriuretic peptides testing is not fully validated yet. PMID- 27387366 TI - Esophageal Atresia with Tracheoesophageal Fistula. PMID- 27387367 TI - Dietary Zinc Intake and Plasma Zinc Concentrations in Children with Short Stature and Failure to Thrive. AB - BACKGROUND: The burden of zinc deficiency on children includes an increased incidence of diarrhea, failure to thrive (FTT) and short stature. The aim of this study was to assess whether children with FTT and/or short stature have lower dietary zinc intake and plasma zinc concentrations compared to controls. METHODS: A case-control study conducted at the American University of Beirut Medical Center included 161 subjects from 1 to 10 years of age. RESULTS: Cases had a statistically significant lower energy intake (960.9 vs. 1,135.2 kcal for controls, p = 0.010), lower level of fat (30.3 vs. 36.5 g/day, p = 0.0043) and iron intake (7.4 vs. 9.1 mg/day, p = 0.034). There was no difference in zinc, copper, carbohydrate and protein intake between the 2 groups. The plasma zinc concentration did not differ between the cases and controls (97.4 vs. 98.2 MUg/dl, p = 0.882). More cases had mild-to-moderate zinc deficiency when compared to controls with 10.3 vs. 3.6%, p = 0.095. CONCLUSION: Our study did not show statistically significant difference in dietary zinc intake and plasma zinc concentrations between children with FTT and/or short stature compared to healthy controls. A prospective study is planned to assess the effect of zinc supplementation on growth parameters in FTT children. PMID- 27387368 TI - Extracellular DNases of Ralstonia solanacearum modulate biofilms and facilitate bacterial wilt virulence. AB - Ralstonia solanacearum is a soil-borne vascular pathogen that colonizes plant xylem vessels, a flowing, low-nutrient habitat where biofilms could be adaptive. Ralstonia solanacearum forms biofilm in vitro, but it was not known if the pathogen benefits from biofilms during infection. Scanning electron microscopy revealed that during tomato infection, R. solanacearum forms biofilm-like masses in xylem vessels. These aggregates contain bacteria embedded in a matrix including chromatin-like fibres commonly observed in other bacterial biofilms. Chemical and enzymatic assays demonstrated that the bacterium releases extracellular DNA in culture and that DNA is an integral component of the biofilm matrix. An R. solanacearum mutant lacking the pathogen's two extracellular nucleases (exDNases) formed non-spreading colonies and abnormally thick biofilms in vitro. The biofilms formed by the exDNase mutant in planta contained more and thicker fibres. This mutant was also reduced in virulence on tomato plants and did not spread in tomato stems as well as the wild-type strain, suggesting that these exDNases facilitate biofilm maturation and bacterial dispersal. To our knowledge, this is the first demonstration that R. solanacearum forms biofilms in plant xylem vessels, and the first documentation that plant pathogens use DNases to modulate their biofilm structure for systemic spread and virulence. PMID- 27387369 TI - The Lost Elements: The Periodic Table's Shadow Side. PMID- 27387370 TI - Graphene Quantum Capacitors for High Frequency Tunable Analog Applications. AB - Graphene quantum capacitors (GQC) are demonstrated to be enablers of radio frequency (RF) functions through voltage-tuning of their capacitance. We show that GQC complements MEMS and MOSFETs in terms of performance for high frequency analog applications and tunability. We propose a CMOS compatible fabrication process and report the first experimental assessment of their performance at microwaves frequencies (up to 10 GHz), demonstrating experimental GQCs in the pF range with a tuning ratio of 1.34:1 within 1.25 V, and Q-factors up to 12 at 1 GHz. The figures of merit of graphene variable capacitors are studied in detail from 150 to 350 K. Furthermore, we describe a systematic, graphene specific approach to optimize their performance and predict the figures of merit achieved if such a methodology is applied. PMID- 27387371 TI - Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling. AB - Laser capture microscopy (LCM) coupled with global transcriptome profiling could enable precise analyses of cell populations without the need for tissue dissociation, but has so far required relatively large numbers of cells. Here we report a robust and highly efficient strategy for LCM coupled with full-length mRNA-sequencing (LCM-seq) developed for single-cell transcriptomics. Fixed cells are subjected to direct lysis without RNA extraction, which both simplifies the experimental procedures as well as lowers technical noise. We apply LCM-seq on neurons isolated from mouse tissues, human post-mortem tissues, and illustrate its utility down to single captured cells. Importantly, we demonstrate that LCM seq can provide biological insight on highly similar neuronal populations, including motor neurons isolated from different levels of the mouse spinal cord, as well as human midbrain dopamine neurons of the substantia nigra compacta and the ventral tegmental area. PMID- 27387372 TI - Feasibility Testing of the Alert for AFib Intervention. AB - Improving early detection and treatment of atrial fibrillation (AF) is critical because untreated AF is a major contributor to stroke and heart failure. We sought to generate knowledge about the feasibility of conducting a randomized controlled trial to test the effect of the Alert for AFib intervention on knowledge, attitudes, and beliefs about treatment-seeking for signs and symptoms of AF. Adults >=65 years old (96% White) at risk for developing AF were randomized to receive the Alert for AFib intervention ( n = 40) or an attention control session ( n = 40). Feasibility goals for recruitment, participant retention, adherence, perceived satisfaction and burden, and intervention fidelity were met. From baseline to study completion, knowledge ( p = .005) and attitudes ( p < .001) about treatment-seeking improved more in the intervention group compared with the control group. Results support testing the effectiveness of the Alert for AFib intervention in a large trial. PMID- 27387373 TI - Imiquimod in dermatology: an overview. AB - Imiquimod is an immune response modifier commercially available as a 3.75 and 5% cream. Topical imiquimod stimulates the innate and adaptive immune responses and induces cytokine production. This allows its use for the treatment of a wide variety of benign and malignant skin conditions due to its potential antiviral, antitumor, and immunoregulatory effects. Currently, topical imiquimod is US Food and Drug Administration (FDA)-approved for the treatment of anogenital warts, actinic keratosis, and superficial basal cell carcinomas. However, it has also shown a beneficial effect in the treatment of many other skin disorders. In this review, we describe existing evidence on the mechanism of action of topical imiquimod, its FDA-approved indications, off-label uses, and side effects. PMID- 27387374 TI - Partially protective immunity induced by the 14-3-3 protein from Trichinella spiralis. AB - Trichinellosis, a widespread zoonosis, is considered to be an emerging or re emerging infectious parasitic disease. The development of vaccines to prevent Trichinella infection in domestic animals and humans is important for disease control. In a previous study, we identified Ts14-3-3 as an immunodominant protein from Trichinella spiralis (T. spiralis) adult worms recognized by early infection sera from pigs and mice. In this study, we further confirmed that Ts14-3-3 mRNA is expressed in both adult worms and in the larval stages of T. spiralis. Immunostaining with anti-Ts14-3-3 mouse sera further confirmed that native Ts14-3 3 is highly expressed on the surface of T. spiralis muscle larvae. The immune recognition by infected sera, its expression in both adult and larval stages and its exposure on the surface of the parasite led us to explore Ts14-3-3 as a vaccine antigen. Recombinant Ts14-3-3 formulated with an ISA50v2 adjuvant produced strong total IgG and balanced IgG1 and IgG2a responses in vaccinated mice and stimulated mouse splenocytes to produce high levels of Th1 (INF-gamma, IL-2) and Th2 (IL4, IL5) cytokines. These results indicate that Ts14-3-3 is highly immunogenic and is able to induce balanced Th1/Th2 immune responses. These vaccine-induced immune responses resulted in a reduction in muscle larvae of up to 46.2% in vaccinated mice upon subsequent larval challenge relative to the number of larvae in mice received PBS control. The significant reduction in muscle larvae in vaccinated mice suggests that Ts14-3-3 is a promising vaccine target for potential use in domestic pigs to prevent trichinellosis transmission. PMID- 27387375 TI - Histochemical study of the effects on abomasal mucins of Haemonchus contortus or Teladorsagia circumcincta infection in lambs. AB - Previously, chemical analysis of gastric fundic mucin showed that infection of sheep with Haemonchus contortus or Teladorsagia circumcincta changed the proportions of monosaccharides and decreased terminal mucin fucosylation and sialylation. To identify the effects of these parasites on the two mucin secreting cell lineages, fundic and antral tissues were collected for histochemistry from 69 lambs aged from 3-4 to 9-10 months-of-age which had received a single infection of either H. contortus or T. circumcincta and euthanased at Day 21 or 28 post- infection respectively. All fundic tissues were stained separately with: (1) with Periodic Acid Schiff (PAS) for all mucins; (2) Alcian Blue (AB) pH 2.5 for acidic mucins (sialylated and sulphated); (3) AB pH 1 for sulphated mucins and (4) High Iron Diamine (HID) for sulphated mucins. Antral and fundic tissues from 24 lambs were also stained for acidic and neutral mucins or with specific lectins for alpha-1-linked fucose and for alpha-2,3- and alpha 2,6-linked sialic acids. Only mucin sulphation appeared to differ visually in uninfected lambs over this age range: there was weak staining with HID in tissues from lambs 3-6 months-of-age, but was generally more intense in those over 7 months-of-age. Sulphomucins were not apparent in surface mucous cells (SMC) or generally in the upper pits. Sialylomucins were located predominantly in the pits and glands, with small amounts of sialylated mucins in SMC and on the luminal surface, mainly in younger animals up to 6 months-of-age and less in the older animals. Parasitism markedly reduced the predominantly neutral surface mucin5AC of the SMC and pit cells, despite pit elongation in both antrum and fundus, whereas the acidic Muc6 secreted by mucus neck cells (MNC) increased along with MNC hyperplasia. Sulphated mucins were present mainly from the mid-pits downward and heavy staining was more common in older animals. In these sheep, the markedly reduced neutral mucin in the SMC and pit cells in both antrum and fundus contrasts with reported hypersecretion of mucus in the intestine, which is believed to aid in parasite expulsion. It has been proposed that intestinal goblet cell hypersecretion occurs only in resistant animals, therefore reduced mucins in the abomasum may be indicative of susceptibility to abomasal parasites. PMID- 27387376 TI - Getting at the source of distinctive encoding effects in the DRM paradigm: evidence from signal-detection measures and source judgments. AB - Studying Deese-Roediger-McDermott (DRM) lists using a distinctive encoding task can reduce the DRM false memory illusion. Reductions for both distinctively encoded lists and non-distinctively encoded lists in a within-group design have been ascribed to use of a distinctiveness heuristic by which participants monitor their memories at test for distinctive-task details. Alternatively, participants might simply set a more conservative response criterion, which would be exceeded by distinctive list items more often than all other test items, including the critical non-studied items. To evaluate these alternatives, we compared a within group who studied 5 lists by reading, 5 by anagram generation, and 5 by imagery, relative to a control group who studied all 15 lists by reading. Generation and imagery improved recognition accuracy by impairing relational encoding, but the within group did not show greater memory monitoring at test relative to the read control group. Critically, the within group's pattern of list-based source judgments provided new evidence that participants successfully monitored for distinctive-task details at test. Thus, source judgments revealed evidence of qualitative, recollection-based monitoring in the within group, to which our quantitative signal-detection measure of monitoring was blind. PMID- 27387378 TI - SPECT imaging of colorectal cancer by targeting CD133 receptor with 99mTc-labeled monoclonal antibody. AB - BACKGROUND: Previous reports suggested that CD133-positive cells had biological features of cancer stem cells (CSCs). Furthermore, CD133 expression was reported as an unfavorable prognostic factor in patients. Therefore, a new radiolabeled probe, 99mTc labeled AD 133 antibody which binding with CD133 specifically, was developed to noninvasively detect CSCs by SPECT in vivo. METHODS: CD133 expression was evaluated by flow cytometry in three colon cancer cell lines (HCT116, Lovo and DLD1). AC133 antibody and control IgG were conjugated with succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), and then labeled with 99mTc. The new radiolabeled probe was named as 99mTc-SHNH-AC133. The vitro cell binding assays, series SPECT imaging and biodistribution analyses were performed. Flow cytometry, immunofluorescence staining of tumor tissues were carried to verify the in vivo imaging results. RESULTS: 99mTc-SHNH-AC133 was labeled with a high radiochemical purity (97.7+/- 2.4%, n=3) and specific activity (4.07 MBq/MUg). Cellular experiments showed that the labeled AC133 antibody retained with a high binding affinity on CD133-positive cells (HCT116 and Lovo cells). Biodistribution analyses showed high tumor uptake of the tracer in HCT116 and Lovo xenografts (8.82 +/- 0.73 and 7.37 +/- 0.26 %ID/g, respectively, n=4) and high tumor-to-muscle ratios (13.18+/-2.84 and 11.13+/-0.53, respectively, n=4) at 36 h after injection, resulting in high contrast SPECT images with high specific tumor uptake. However, the tumor bearing CD 133-negative cell (DLD1 cells) showed no obvious uptake of 99mTc-SHNH-AC133 both in vitro cell binding and in vivo imaging study. Moreover, the tumor uptake of 99mTc-SHNH-AC133 in positive tumor models was significantly reduced by pre-injection of excess unlabeled AC133 antibody. Flow cytometric analysis and immunofluorescence staining confirmed the CD133 expression in tumors, which correlated well with the in vivo results. CONCLUSION: This study showed that 99mTc-SHNH-AC133 exhibited high uptake in CD133-positive tumors. The high specificity and good tumor targeting properties of 99mTc-SHNH-AC133 may provide a new method to track or locate CSCs. PMID- 27387377 TI - Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro. AB - Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (<= 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level. PMID- 27387379 TI - IntegoTM Infusion System: cost effectiveness analysis focusing on dosimetry, sterility and management. AB - BACKGROUND: Healthcare providers across Europe are facing an ever-growing demand in clinical PET referrals. Currently, it is estimated that the administration of the PET tracer accounts for approximately 40% of the unitary PET procedure reimbursement (uPETr). Although the cost of PET/CT is highly dependant on the radiopharmaceutical cost itself, little is known about the economical impact of the utilized administration method and the repercussions on staff radiation exposure. Our objective was to evaluate the cost- effectiveness of automatic injection/fractionation system IntegoTM (Bayer HealthCare, MEDRAD Europe, Netherlands) for istaff radiation exposure reduction and to validate its use with 18F-choline (FCH). METHODS: In order to validate IntegoTM use with FCH we analyzed sterility, radioactivity fractionation accuracy and radiation protection for staff . We analyzed IntegoTM impact on examination costs and its impact on organization efficiency. A cost-effectiveness analysis (CEA) was estimated as the incremental cost to reduce staff radiation exposure. RESULTS: According to our data, IntegoTM ensures both sterility and accuracy of FCH doses' activity , reducing, at the same time, the exposure to radiation either whole body and at the extremities (94% and 75% respectively for the technicians and complete reduction for physicians). IntegoTM's variable unit costs are higher than the SA (respectively 1,8% and 0.4% of PET reimbursement), while staff costs are significantly higher with SA (respectively 0.27% and 1.57% of unitary PET reimbursement [uPETr]). In our simulation, based on a 2,450 PET yearly output, the differential costs were slightly higher by using IntegoTMTM (+ 14%). The incremental cost-effectiveness ratio (ICER) was equal to 1.1, i.e. the healthcare provider pays an additional cost of 0.38% of uPETr to obtain a significant reduction of staff radiation exposure (-4.5 MUS). CONCLUSION: IntegoTM, for its favorable results in terms of cost effectiveness, could be a useful tool in a nuclear medicine department, limiting the staff radiation exposure. PMID- 27387380 TI - The effects of androgen deprivation therapy on the 18F-choline uptake in prostate cancer patients undergoing neoadjuvant treatment. AB - BACKGROUND: To evaluate how neoadjuvant androgen deprivation therapy (ADT) can impact 18F- Choline uptake in primary prostate cancer (PC) and its metastases before radical prostatectomy (RP) or radiation therapy (RT). METHODS: We retrospectively reviewed images of 79 PC patients undergoing 18F-Choline PET/CT before RP or RT. Based on concomitant administration of neoadjuvant ADT at the time of 18F-Choline PET/CT, patients were subdivided into naive group (Group 1) and neoadjuvant ADT group (Group 2). PET/CT results, SUVmax and metabolic tumor volume (MTV) for each site were re-assessed by two nuclear medicine physicians with more than 5 years of experience. A chi-square and a U-Mann Whitney test were used to compare the two groups. RESULTS: Sixty-two patients were included in Group 1, while 17 in Group 2. PET/CT was positive in all patients, in particular: 54 had a significant uptake in prostate alone, 12 in prostate plus lymph nodes (LN), 4 in prostate plus LN and bone, 3 in prostate plus bone and 6 in prostate plus other organs (such as lung or thyroid). PET/CT was more frequently positive in a different site, outside the prostate, in Group 1 as compared to Group 2 (p<0.001). Conversely, median SUVmax and MTV in the prostate resulted significantly lower in Group 2 than in Group 1 (5.34 vs 7.72 and 3.66 vs. 6.86 cm3, respectively; both p<0.05). CONCLUSION: PET/CT could have an important role in prostate cancer staging before primary treatment; however, before imaging, hormonal therapy status should be carefully evaluated. PMID- 27387381 TI - Experimental Phage Therapy for Burkholderia pseudomallei Infection. AB - Burkholderia pseudomallei is an intracellular Gram-negative bacterial pathogen intrinsically resistant to a variety of antibiotics. Phages have been developed for use as an alternative treatment therapy, particularly for bacterial infections that do not respond to conventional antibiotics. In this study, we investigated the use of phages to treat cells infected with B. pseudomallei. Phage C34 isolated from seawater was purified and characterised on the basis of its host range and morphology using transmission electron microscopy (TEM). Phage C34 was able to lyse 39.5% of B. pseudomallei clinical strains. Due to the presence of contractile tail, phage C34 is classified as a member of the family Myoviridae, a tailed double-stranded DNA virus. When 2 * 105 A549 cells were exposed to 2 * 107 PFU of phage C34, 24 hours prior to infection with 2 * 106 CFU of B. pseudomallei, it was found that the survivability of the cells increased to 41.6 +/- 6.8% as compared to 22.8 +/- 6.0% in untreated control. Additionally, application of phage successfully rescued 33.3% of mice infected with B. pseudomallei and significantly reduced the bacterial load in the spleen of the phage-treated mice. These findings indicate that phage can be a potential antimicrobial agent for B. pseudomallei infections. PMID- 27387382 TI - No bed sharing or safer bed sharing? PMID- 27387383 TI - Colloidal Properties of Aqueous Poly(vinyl acetate)-Borate Dispersions with Short Chain Glycol Ethers. AB - We report the influence of adding five short-chain glycol ethers (SCGEs) on the structure, stability, and viscoelastic properties of aqueous dispersions of partially hydrolyzed poly(vinyl acetate) and borax. The properties of these gel like materials have been investigated as a function of the structure of the added SCGE both below and above the critical aggregation (or micellar) concentrations using (11) B and (13) C NMR, rheology, and small-angle neutron scattering. The results indicate that the SCGE aggregation behavior is not affected by incorporation into the gel-like network. However, changes in the viscoelasticity and structural properties of the dispersions were detected that can be correlated to the nature of the solvent system. Also, the ability of these materials to clean an unvarnished acrylic paint surface coated with synthetic soil has been evaluated using colorimetery, and the surface of the dispersion after cleaning was visualized with scanning electron microscopy. PMID- 27387384 TI - A unique chromosomal in-frame deletion identified among seven XP-C patients. AB - BACKGROUND: The nucleotide excision repair (NER) pathway, defective in xeroderma pigmentosum (XP) patients, removes DNA photolesions in order to prevent carcinogenesis. Complementation group C (XP-C) is the most frequent group of XP patients worldwide. METHODS: We analyzed seven XP-C patients clinically and molecular-genetically applying: post-UV cell survival (MTT-assay), quantitative Real-time PCR, sequencing on chromosomal as well as cDNA level, and in silico interpretation of sequencing data. RESULTS: All cases displayed diminished post UV cell survival as well as reduced XPC mRNA levels. Five homozygous and two heterozygous disease causing mutations were identified. A large chromosomal deletion of ~5.8 kb identified in XP174MA leads to an unique in frame deletion of XPC exon 2 and exon 3. In silico analysis revealed the deletion of 102 amino acids in the N-terminal part of XPC while leaving the C-terminal domain intact. The novel c.361delA mutation in XP168MA leads to a frameshift in exon 3 resulting in a premature stop codon 27 codons downstream of the deleted adenine. CONCLUSION: Our analysis confirms that XP-C patients without increased sun sensitivity develop non-melanoma skin cancers earlier than sun-sensitive XP-C patients. Reduced cellular mRNA levels are characteristic for XP complementation group C and qRT-PCR represents a rapid diagnostic tool. PMID- 27387386 TI - Clinical Psychopharmacology Update: What's in a Name? Confusion Prompts Change for Vortioxetine's Brand Name. AB - Similar names between two unrelated drugs have led the FDA to issue warnings about and now approve a name change for vortioxetine, which was branded as Brintellix(r) until recently. While the trade name had been screened prior to the product's launch, the FDA received numerous reports of prescribing and dispensing errors, specifically with regard to the anti-coagulant drug Brilinta(r) (ticagrelor). Starting 1 June 2016, vortioxetine will be marketed under the name TrintellixTM in an effort to reduce confusion. Clinicians are advised that while the name and National Drug Code number with this product will change, it will retain the same formulation, indication, and dosage information. To the extent possible, clinicians can and should take actions to identify and reduce potential medication errors in prescriptions, especially when using electronic records and e-prescription systems. PMID- 27387385 TI - Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. METHODS: Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias. RESULTS: We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. CONCLUSIONS: This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA. PMID- 27387387 TI - The role of myocardin-related transcription factor-A in Abeta25-35 induced neuron apoptosis and synapse injury. AB - Myocardin-related transcription factor-A (MRTF-A) highly expressed in brain has been demonstrated to promote neuronal survival via regulating the transcription of related target genes as a powerful co-activator of serum response factor (SRF). However, the role of MRTF-A in Alzheimer's disease (AD) is still unclear. Here, we showed that MRTF-A was significantly downregulated in cortex of the Abeta25-35-induced AD rats, which played a key role in Abeta25-35 induced cerebral neuronal degeneration in vitro. Bilateral intracerebroventricular injection of Abeta25-35 caused significantly MRTF-A expression decline in cortex of rats, along with significant neuron apoptosis and plasticity damage. In vitro, transfection of MRTF-A into primary cultured cortical neurons prevented Abeta25 35 induced neuronal apoptosis and synapses injury. And luciferase reporter assay determined that MRTF-A could bind to and enhance the transactivity of the Mcl-1 (Myeloid cell leukemia-1) and Arc (activity-regulated cytoskeletal-associated protein) promoters by activating the key CArG box element. These data demonstrated that the decreasing of endogenous MRTF-A expression might contribute to the development of AD, whereas the upregulation MRTF-A in neurons could effectively reduce Abeta25-35 induced synapse injury and cell apoptosis. And the underlying mechanism might be partially due to MRTF-A-mediated the transcription and expression of Mcl-1 and Arc by triggering the CArG box. PMID- 27387388 TI - Identification and Validation of HCC-specific Gene Transcriptional Signature for Tumor Antigen Discovery. AB - A novel two-step bioinformatics strategy was applied for identification of signatures with therapeutic implications in hepatitis-associated HCC. Transcriptional profiles from HBV- and HCV-associated HCC samples were compared with non-tumor liver controls. Resulting HCC modulated genes were subsequently compared with different non-tumor tissue samples. Two related signatures were identified, namely "HCC-associated" and "HCC-specific". Expression data were validated by RNA-Seq analysis carried out on unrelated HCC samples and protein expression was confirmed according to The Human Protein Atlas" (http://proteinatlas.org/), a public repository of immunohistochemistry data. Among all, aldo-keto reductase family 1 member B10, and IGF2 mRNA-binding protein 3 were found strictly HCC-specific with no expression in 18/20 normal tissues. Target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles. The described novel strategy showed to be feasible for identification of HCC-specific proteins as highly potential target for HCC immunotherapy. PMID- 27387389 TI - Riboflavin Phototransformation on the Changes of Antioxidant Capacities in Phenolic Compounds. AB - Eight phenolic compounds including: p-coumaric acid, vanillic acid, caffeic acid, chlorogenic acid, trolox, quercetin, curcumin, and resveratrol were treated with riboflavin (RF) photosensitization and in vitro antioxidant capacities of the mixtures were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2' azino bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Mixtures containing p-coumaric acid and vanillic acid under RF photosensitization showed increases in ferric ion reducing ability and radical scavenging activity of DPPH, whereas mixtures of other compounds had decreases in both radical scavenging ability and ferric reducing antioxidant power. Hydroxycoumaric acid and conjugated hydroxycoumaric and coumaric acids were tentatively identified from RF photosensitized p-coumaric acid, whereas dimmers of vanillic acid were tentatively identified from RF photosensitized vanillic acid. RF photosensitization may be a useful method to enhance antioxidant properties like ferric ion reducing abilities of some selected phenolic compounds. PMID- 27387390 TI - Iodine-Mediated Domino Oxidative Cyclization: One-Pot Synthesis of 1,3,4 Oxadiazoles via Oxidative Cleavage of C(sp(2))-H or C(sp)-H Bond. AB - An I2-promoted, metal-free domino protocol for one-pot synthesis of 1,3,4 oxadiazoles has been developed via oxidative cleavage of C(sp(2))-H or C(sp)-H bonds, followed by cyclization and deacylation. In this reaction, the use of K2CO3 as a base is found to be an essential factor in the cyclization and the C-C bond cleavage. This procedure proceeded smoothly in moderate to high yields with good functional group compatibility. PMID- 27387393 TI - Correlating synergistic reinforcement with chain motion in elastomer/nanocarbon hybrids composites. AB - The strategy of using hybrid fillers with different geometric shapes and aspect ratios has been established to be an efficient way to achieve high-performance polymer composites. While, in spite of the recently renowned advances in this field, the mechanism of synergistic behavior in the system is still unclear and equivocal. In this study, we systematically investigated the mechanism for the synergistic reinforcement in an elastomer reinforced by nanocarbon hybrids consisting of 2D reduced graphene oxide (rGO) and 1D carbon nanotubes (CNTs). The improved dispersion state of hybrid filler was attested by Raman, UV-Vis spectra and morphological observations. In addition to the phenomenological evidences, we substantiated a stronger confinement effect of hybrid network on chain dynamics, for the first time, with molecular concepts by dielectric relaxation analysis. The formation of a glassy interphase with orders of magnitude slower chain dynamics than that for bulk chains has been explicitly demonstrated in the hybrid system. Besides improved dispersion upon hybridization, it is believed the formation of a glassy interphase is another crucial factor in governing the synergistic reinforcement capability of hybrid composites. We envision this new finding provides significant insight into the mechanism of synergistic behavior in hybrid-filled polymer composites with molecular concepts. PMID- 27387392 TI - Seroma Cytology in Breast Cancer: An Underappreciated Issue. AB - BACKGROUND: The presence of malignant cells in postoperative seroma has been ignored in current breast cancer treatment. We aimed to assess the presence of malignant seroma cytology and to evaluate its relationship with the known prognostic factors for breast cancer. PATIENTS AND METHODS: The solution from irrigation of the operation field and postoperative drainage fluid from 68 patients were prospectively collected and examined for malignant cytology. The results were evaluated according to the tumor characteristics and patient demographics. RESULTS: Malignant cytology was found in none of the intraoperative samples but was found in the postoperative samples from 4 patients. Of these 4 patients, 3 were free of axillary metastasis. None of the common risk factors for breast cancer was associated with the finding of malignant cytology. CONCLUSION: Malignant cells can be seen in the drainage fluids from breast cancer patients independent of any contamination occurring during surgery, even in those without axillary metastasis. PMID- 27387394 TI - Pantomime Production by People With Aphasia: What Are Influencing Factors? AB - PURPOSE: The present article aimed to inform clinical practice on whether people with aphasia (PWA) deploy pantomime techniques similarly to participants without brain damage (PWBD) and if not, what factors influence these differences. METHOD: We compared 38 PWA to 20 PWBD in their use of 6 representation techniques (handling, enact, object, shape, deictic, and other) when pantomiming objects, and determined whether PWA used the same defaults as PWBD. We assessed the influence of (non-)dominant arm use, ideomotor apraxia, semantic processing, aphasia severity, and oral naming. RESULTS: PWA used various pantomime techniques. Enact, deictic, and other were used infrequently. No differences were found for the use of shape techniques, but PWA used fewer handling and object techniques than PWBD and they did not use these for the same objects as PWBD did. No influence was found for (non-)dominant arm use. All other variables correlated with the use of handling, object, and defaults. CONCLUSION: In our study, PWA were able to use various pantomime techniques. As a group, they used these techniques differently from PWBD and relied more heavily on the use of shape techniques. This was not influenced by a hemiparesis, but seemed dependent on semantic processing. Clinical implications are discussed. PMID- 27387395 TI - Implementing an Ebola Vaccine Study - Sierra Leone. AB - In October 2014, the College of Medicine and Allied Health Sciences of the University of Sierra Leone, the Sierra Leone Ministry of Health and Sanitation, and CDC joined the global effort to accelerate assessment and availability of candidate Ebola vaccines and began planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). STRIVE was an individually randomized controlled phase II/III trial to evaluate efficacy, immunogenicity, and safety of the recombinant vesicular stomatitis virus Ebola vaccine (rVSV-ZEBOV). The study population was health care and frontline workers in select chiefdoms of the five most affected districts in Sierra Leone. Participants were randomized to receive a single intramuscular dose of rVSV-ZEBOV at enrollment or to receive a single intramuscular dose 18-24 weeks after enrollment. All participants were followed up monthly until 6 months after vaccination. Two substudies separately assessed detailed reactogenicity over 1 month and immunogenicity over 12 months. During the 5 months before the trial, STRIVE and partners built a research platform in Sierra Leone comprising participant follow-up sites, cold chain, reliable power supply, and vaccination clinics and hired and trained at least 350 national staff. Wide-ranging community outreach, informational sessions, and messaging were conducted before and during the trial to ensure full communication to the population of the study area regarding procedures and current knowledge about the trial vaccine. During April 9-August 15, 2015, STRIVE enrolled 8,673 participants, of whom 453 and 539 were also enrolled in the safety and immunogenicity substudies, respectively. As of April 28, 2016, no Ebola cases and no vaccine-related serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability, were reported in the study population. Although STRIVE will not produce an estimate of vaccine efficacy because of low case frequency as the epidemic was controlled, data on safety and immunogenicity will support decisions on licensure of rVSV-ZEBOV.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west africa/partners.html). PMID- 27387396 TI - Protective effect of the essential oil of Zanthoxylum myriacanthum var. pubescens against dextran sulfate sodium-induced intestinal inflammation in mice. AB - BACKGROUND: Zanthoxylum myriacanthum var. pubescens is an ethnic medicine for digestive disease known as Maqian. A previous report showed that the Maqian fruits essential oil (MQEO) exhibited an NO inhibitory effect on RAW 264.7 cells, but the effect on inflammatory disease in vivo remains unknown. PURPOSE: To investigate the anti-inflammatory effect of Z. myriacanthum var. pubescens as potential candidate for the treatment of intestinal inflammation. STUDY DESIGN: Evaluation of anti-inflammatory effect of MQEO using dextran sulfate sodium (DSS) induced intestinal inflammation in mice and exploration of the mechanisms with THP-1 cells. METHODS: C57BL/6 mice were provided drinking water containing 3% DSS for 10 days followed by normal drinking water for 3 days. MQEO (35 and 70mg/kg) were given 5 days before experiments and continued for another 13 days. At the end of experiments, mice were euthanized and colonic tissue was collected to be analyzed by H&E staining, RT-PCR and immunohistochemistry for evaluating the damage of colons, the mRNA levels of IL-1beta, IL-6, IL-12p35 and TNF-alpha, and the expressions of myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). The LPS-stimulated THP-1 cell line was used for exploring the role of inflammatory markers using ELISA, western blot and flow cytometry methods. RESULTS: Oral administration of MQEO (35 and 70mg/kg) markedly attenuated the symptoms of intestinal inflammation, including diarrhea, rectal bleeding, and loss of body weight. It also reduced the shortening of colon length and histopathological damage. The expressions of MPO and MMP-9 and the mRNA levels of pro-inflammatory cytokines (IL-1beta, IL-6 and IL-12p35) in colonic tissue significantly decreased after MQEQ treatment. The activation of NF-kappaB p65 in colonic mucosa was also markedly suppressed. In addition, MQEO significantly suppressed LPS-stimulated production of TNF-alpha and IL-1beta, effectively blocked phosphorylation of IKK and IkappaB, and dose-dependently reduced LPS stimulated expression of TLR4 in THP-1 cells at concentrations ranging from 0.010/00 to 0.050/00 (v/v). CONCLUSION: MQEO exhibited protective effect against DSS-induced intestinal inflammation and the anti-inflammatory activity may be associated with TLR4 mediated NF-kappaB signaling pathway, suggesting it might be used as an anti-inflammatory agent. PMID- 27387397 TI - Protective effects of marein on high glucose-induced glucose metabolic disorder in HepG2 cells. AB - BACKGROUND: Our previous study has shown that Coreopsis tinctoria increases insulin sensitivity and regulates hepatic metabolism in high-fat diet (HFD) induced insulin resistance rats. However, it is unclear whether or not marein, a major compound of C. tinctoria, could improve insulin resistance. Here we investigate the effect and mechanism of action of marein on improving insulin resistance in HepG2 cells. METHODS: We investigated the protective effects of marein in high glucose-induced human liver carcinoma cell HepG2. In kinase inhibitor studies, genistein, LY294002, STO-609 and compound C were added to HepG2 cells 1h before the addition of marein. Transfection with siRNA was used to knock down LKB1, and 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose (2-NBDG), an effective tracer, was used to detect glucose uptake. RESULTS: The results showed for the first time that marein significantly stimulates the phosphorylation of AMP-activated protein kinase (AMPK) and the Akt substrate of 160kDa (AS160) and enhanced the translocation of glucose transporter 1 (GLUT1) to the plasma membrane. Further study indicated that genistein (an insulin receptor tyrosine kinase inhibitor) altered the effect of marein on glucose uptake, and both LY294002 (a phosphatidylinositol 3-kinase inhibitor) and compound C (an AMP-activated protein kinase inhibitor) significantly decreased marein-stimulated 2-NBDG uptake. Additionally, marein-stimulated glucose uptake was blocked in the presence of STO-609, a CaMKK inhibitor; however, marein stimulated AMPK phosphorylation was not blocked by LKB1 siRNA in HepG2 cells. Marein also inhibited the phosphorylation of insulin receptor substrate (IRS-1) at Ser 612, but inhibited GSK-3beta phosphorylation and increased glycogen synthesis. Moreover, marein significantly decreased the expression levels of FoxO1, G6Pase and PEPCK. CONCLUSIONS: Consequently, marein improved insulin resistance induced by high glucose in HepG2 cells through CaMKK/AMPK/GLUT1 to promote glucose uptake, through IRS/Akt/GSK-3beta to increase glycogen synthesis, and through Akt/FoxO1 to decrease gluconeogenesis. Marein could be a promising leading compound for the development of hypoglycemic agent or developed as an adjuvant drug for diabetes mellitus. PMID- 27387398 TI - Intestinal anti-inflammatory effects of total alkaloid extract from Fumaria capreolata in the DNBS model of mice colitis and intestinal epithelial CMT93 cells. AB - BACKGROUND: Fumaria capreolata L. (Papaveraceae) is a botanical drug used in North Africa for its gastro-intestinal and anti-inflammatory properties. It is characterized for the presence of several alkaloids that could be responsible for some of its effects, including an immunomodulatory activity. PURPOSE: To test in vivo the intestinal anti-inflammatory properties of the total alkaloid fraction extracted from the aerial parts of F. capreolata (AFC), and to evaluate its effects on an intestinal epithelial cell line. STUDY DESIGN AND METHODS: AFC was chemically characterized by liquid chromatography coupled to diode array detection and high resolution mass spectrometry. Different doses of AFC (25, 50 and 100mg/kg) were assayed in the DNBS model of experimental colitis in mice, and the colonic damage was evaluated both histologically and biochemically. In addition, in vitro experiments were performed with this alkaloid fraction on the mouse intestinal epithelial cell line CMT93 stimulated with LPS. RESULTS: The chemical analysis of AFC revealed the presence of 23 alkaloids, being the most abundants stylopine, protopine and coptisine. Oral administration of AFC produced a significant inhibition of the release and the expression of IL-6 and TNF-alpha in the colonic tissue. It also suppressed in vivo the transcription of other pro inflammatory mediators such as IL-1beta, iNOS, IL-12 and IL-17. Furthermore, AFC showed an immunomodulatory effect in vitro since it was able to inhibit the mRNA expression of IL-6, TNF-alpha and ICAM-1. Moreover, the beneficial effect of AFC in the colitic mice could also be associated with the normalization of the expression of MUC-2 and ZO-1, which are important for the intestinal epithelial integrity. CONCLUSION: The present study suggests that AFC, containing 1.3% of stylopine and 0.9% of protopine, significantly exerted intestinal anti inflammatory effects in an experimental model of mouse colitis. This fact could be related to a modulation of the intestinal immune response and a restoration of the intestinal epithelial function. PMID- 27387399 TI - In vivo antitumor effect, induction of apoptosis and safety of Remirea maritima Aubl. (Cyperaceae) extracts. AB - BACKGROUND: Remirea maritima has been widely used in the treatment of diarrhea, kidney disease, and high fever and for therapeutic purposes, such as an analgesic and anti-inflammatory. However, few scientific research studies on its medicinal properties have been reported. PURPOSE: The present study aimed to investigate the anticancer potential of aqueous extract (AE), 40% hydroalcoholic extracts (40HA) and 70% (70HA) from R. maritima in experimental models and to identify its phytochemical compounds. METHODS: The chemical composition of AE, 40HA and 70HA was assessed by HPLC-DAD and ESI-IT-MS/MS. In vitro activity was determined on cultured tumor cell, NCI-H385N (Broncho-alveolar carcinoma), OVCAR-8 (Ovarian carcinoma) and PC-3M (prostate carcinoma) by the MTT assay, and the in vivo antitumor activity was assessed in Sarcoma 180-bearing mice. Toxicological parameters were also evaluated as well as the humoral immune response. RESULTS: Among the aqueous and hydroalcoholic extracts of R. maritima, only 40HA showed in vitro biological effect potential, presenting IC50 values of 27.08, 46.62 and >50ug/ml for OVCAR-8, NCI-H385M and PC-3M cells lines, respectively. Regarding chemical composition, a mixture of isovitexin-2''-O-beta-D-glucopyranoside, vitexin-2''-O-beta-D-glucopyranoside, luteolin-7-O-glucuronide and 1-O-(E) caffeoyl-beta-D-glucose were identified as the major phytochemical compounds of the extracts. In the in vivo study, the tumor inhibition rates were 57.16-62.57% at doses of 25mg/kg and 50mg/kg, respectively, and the tumor morphology presented increasing numbers of apoptotic cells. Additionally, 40HA also demonstrated significantly increased of OVA-specific total Ig. CONCLUSIONS: 40HA exhibited in vitro and in vivo anticancer properties without substantial toxicity that could be associated with its immunostimulating properties. PMID- 27387400 TI - Reversal of diabetes-induced behavioral and neurochemical deficits by cinnamaldehyde. AB - BACKGROUND: Chronic hyperglycemia during diabetes is associated with altered cognitive function. Cinnamaldehyde showed to have many pharmacological activities indicating anti-diabetic, cognitive enhancer, antiinflammatory etc. In the present study, we have investigated the effects of cinnamaldehyde (CA) on diabetes-induced cognitive deficits. METHODS: Diabetes was induced in Sprague Dawley rats using high fat diet followed by streptozotocin (35mg/kg, i.p.). High fat diet feeding was continued for 18 week after STZ administration. CA was administered daily during the last 3 weeks (week 16-18) at a doses of 10, 20 and 40mg/kg (p.o.). Animals were subjected to behavioral tests during 18th week. Neurotransmitter levels (glutamate and GABA), acetylcholine esterase (AChE) activity and inflammatory markers (TNF-alpha and IL-6) were assessed in the hippocampus and cortex. RESULTS: Vehicle-treated diabetic rats showed impaired behavior in open field, elevated plus maze and water maze test compared to age matched control rats. Cinnamaldehyde showed significant reduction in blood glucose levels at dose of 20 and 40mg/kg. Three weeks treatments of cinnamaldehyde showed significant amelioration of behavioral deficits in diabetic rats. Chronic treatment with cinnamaldehyde showed improvement in brain ChE activity, neurotransmitter levels and reduction in IL-6 and TNF-alpha levels. CONCLUSION: The present study demonstrates that treatment with cinnamaldehyde reverse neuroinflammation and changes in neurotransmitter levels, and consequently improves behavioral deficits in diabetic rats. PMID- 27387401 TI - Clivorine, an otonecine pyrrolizidine alkaloid from Ligularia species, impairs neuronal differentiation via NGF-induced signaling pathway in cultured PC12 cells. AB - BACKGROUND: Pyrrolizidine alkaloids (PAs) are commonly found in many plants including those used in medical therapeutics. The hepatotoxicities of PAs have been demonstrated both in vivo and in vitro; however, the neurotoxicities of PAs are rarely mentioned. PURPOSE: In this study, we aimed to investigate in vitro neurotoxicities of clivorine, one of the PAs found in various Ligularia species, in cultured PC12 cells. STUDY DESIGN: PC12 cell line was employed to first elucidate the neurotoxicity and the underlying mechanism of clivorine, including cell viability and morphology change, neuronal differentiation marker and signaling pathway. METHODS: PC12 cells were challenged with series concentrations of clivorine and/or nerve growth factor (NGF). The cell lysates were collected for MTT assay, trypan blue staining, immunocytofluorescent staining, qRT-PCR and western blotting. RESULTS: Clivorine inhibited cell proliferation and neuronal differentiation evidenced by MTT assay and dose-dependently reducing neurite outgrowth, respectively. In addition, clivorine decreased the level of mRNAs encoding for neuronal differentiation markers, e.g. neurofilaments and TrkA (NGF receptor). Furthermore, clivorine reduced the NGF-induced the phosphorylations of TrkA, protein kinase B and cAMP response element-binding protein in cultured PC12 cells. CONCLUSION: Taken together, our results suggest that clivorine might possess neurotoxicities in PC12 cells via down-regulating the NGF/TrkA/Akt signaling pathway. PAs not only damage the liver, but also possess neurotoxicities, which could possibly result in brain disorders, such as depression. PMID- 27387402 TI - Psoralidin induced reactive oxygen species (ROS)-dependent DNA damage and protective autophagy mediated by NOX4 in breast cancer cells. AB - BACKGROUND: Psoralidin (PSO), a natural phenolic coumarin, was reported to have anti-cancer activities. PSO induced reactive oxygen species (ROS) generation in cancer cells. The role of ROS in its anti-cancer effect remains unclear. PURPOSE: This study was designed to investigate the potential roles of ROS in PSO-induced anti-cancer effect in MCF-7 breast cancer cells. METHODS: Effect of PSO on cancer cell proliferation was determined by MTT assay. Comet assay was used to determine DNA damage. Protein expression was detected by Western blotting. Autophagic vacuoles were detected by monodansylcadaverine (MDC) staining. ROS generation was measured by fluorescent probe. NOX4 localization was determined by immunofluorescence staining. RESULTS: PSO treatment caused proliferation inhibition in time- and dose- dependent manners, which was partially reversed by N-acetyl cysteine (NAC) and diphenyleneiodonium (DPI). PSO induced DNA damage and increased protein expression of gamma-H2AX, phosphorylation of ATM, ATR, Chk1, and Chk2. PSO induced autophagy as evidenced by the accumulation of autophagic vacuoles and alterations of autophagic protein expression. PSO-induced cell death was enhanced by autophagy inhibitor chloroquine (CQ). Furthermore, PSO treatment induced ROS formation, which was reversed by NAC or DPI pretreatment. The expression of NOX4 was significantly enhanced by PSO. Both NAC and DPI could reverse PSO-induced DNA damage and autophagic responses. In addition, silencing NOX4 by siRNA inhibited PSO-induced ROS generation, DNA damage, and autophagy. CONCLUSIONS: Taken together, these results showed that PSO induced DNA damage and protective autophagy mediated by ROS generation in a NOX4-dependent manner in MCF 7 cells. PMID- 27387403 TI - Docking, characterization and investigation of beta-cyclodextrin complexed with citronellal, a monoterpene present in the essential oil of Cymbopogon species, as an anti-hyperalgesic agent in chronic muscle pain model. AB - BACKGROUND: Citronellal (CT) is a monoterpene with antinociceptive acute effect. beta-Cyclodextrin (betaCD) has enhanced the analgesic effect of various substances. HYPOTHESIS/PURPOSE: To evaluate the effect of CT both complexed in beta-cyclodextrin (CT-betaCD) and non-complexed, in a chronic muscle pain model (CMP) in mice. STUDY DESIGN: The complex containing CT in betaCD was obtained and characterized in the laboratory. The anti-hyperalgesic effect of CT and CT-betaCD was evaluated in a pre-clinical in vivo study in a murine CMP. METHODS: The complex was characterized through differential scanning calorimetry, derivative thermogravimetry, moisture determination, infrared spectroscopy and scanning electron microscopy. Male Swiss mice were pre-treated with CT (50mg/kg, po), CT betaCD (50mg/kg, po), vehicle (isotonic saline, po) or standard drug (tramadol4 mg/kg, ip). 60 min after the treatment and then each 1h, the mechanic hyperalgesia was evaluated to obtain the time effect. In addition, the muscle strength using grip strength meter and hyperalgesia were also performed daily, for 7 days. We assessed by immunofluorescence for Fos protein on brains and spinal cords of mice. The involvement of the CT with the glutamatergic system was studied with molecular docking. RESULTS: All characterization methods showed the CT-betaCD complexation. CT-induced anti-hyperalgesic effect lasted until 6h (p <0.001) while CT-betaCD lasted until 8h (p <0.001vs vehicle and p <0.001vs CT from the 6th h). CT-betaCD reduced mechanical hyperalgesia on all days of treatment (p <0.05), without changing muscle strength. Periaqueductal gray (p <0.01) and rostroventromedular area (p <0.05) showed significant increase in the Fos protein expression while in the spinal cord, there was a reduction (p <0.001). CT showed favorable energy binding (-5.6 and -6.1) to GluR2-S1S2J protein based in the docking score function. CONCLUSION: We can suggest that betaCD improved the anti-hyperalgesic effect of CT, and that effect seems to involve the descending pain-inhibitory mechanisms, with a possible interaction of the glutamate receptors, which are considered as promising molecules for the management of chronic pain such as CMP. PMID- 27387404 TI - Probing the impact of quercetin-7-O-glucoside on influenza virus replication influence. AB - BACKGROUND: Influenza virus is still at large and seriously affects social welfare and health. Dianthus superbus is a well-known medicinal plant widely used in Mongolian and Chinese traditional medicine for anti-inflammatory purposes. PURPOSE: To investigate the influence of this novel herbal medicinal product over virus infection and virus-induced symptoms METHOD: Quercetin-7-O-glucoside was isolated by bioassay (anti-influenza)-guided fractionation. The structural elucidation was made with 1H-NMR and 13C-NMR. Influenza A/Vic/3/75 (H3N2), A/PR/8/34 (H1N1), B/Maryland/1/59 and B/Lee/40 viruses were used for the evaluation of the antiviral activity. Virus-induced reactive oxygen species and autophagy formation levels were studied. The antiviral mechanism was elucidated via time-dependent, pre-, post-incubation assay methods. The viral RNA replication inhibition of Q7G was analyzed using quantitative RT-PCR method. The blocking of polymerase basic protein subunits of influenza viral RNA polymerase by Q7G was detected by in silico molecular docking assays using AutoDock Vina program with m(7)GTP. Additionally, Q7G was tested against M-MuLV RNA polymerase. RESULTS: Q7G was not cytotoxic (CC50>100ug/ml) in MDCK cells and it showed 3.1ug/ml, 6.61ug/ml, 8.19ug/ml and 5.17ug/ml IC50 values against influenza A/PR/8/34, A/Vic/3/75, B/Lee/40 and B/Maryland/1/59 virus strains, respectively. Treatment of Q7G highly reduced ROS and autophagy formation induced by influenza virus infection. Q7G did not reduce NA activity and did not directly interact with the virus particles. Since viral RNA synthesis was blocked by treatment of Q7G. We targeted viral RNA polymerase for further probing. Interestingly, the binding energy of Q7G on viral PB2 protein was -9.1kcal/mol and was higher than m(7)GTP recorded as -7.5kcal/mol. It also was observe to block M-MuLV RNA polymerase. CONCLUSION: Isolated compound Q7G showed strong inhibition activity against influenza A and B viruses. It also reduced virus-induced ROS and autophagy formation. Q7G does not directly bind to the virus particles and did not affect NA activity. These results indicated that Q7G inhibits viral RNA polymerase, and that it occupies the binding site of m(7)GTP on viral PB2 protein. PMID- 27387405 TI - Jatrophane diterpenes and cancer multidrug resistance - ABCB1 efflux modulation and selective cell death induction. AB - BACKGROUND: Modulation of P-glycoprotein (ABCB1) and evaluation of the collateral sensitivity effect are among the most promising approaches to overcome multidrug resistance (MDR) in cancer. In a previous study, two rare 12,17-cyclojatrophanes (1-2) and other novel jatrophanes (3-4), isolated from Euphorbia welwitschii, were screened for collateral sensitivity effect. Herein, the isolation of another jatrophane (5) is presented, being the broader goal of this work to investigate the role of euphowelwitschines A (1) and B (2), welwitschene (3), epoxywelwitschene (4) and esulatin M (5) as ABCB1 modulators and/or collateral sensitivity agents. METHODS: Compounds 1-5 were evaluated for ABCB1 modulation ability through combination of transport and chemosensitivity assays, using a mouse T-lymphoma MDR1-transfected cell model. Moreover, the nature of interaction of compound 4 with ABCB1 was studied, using an ATPase assay. The MDR-selective antiproliferative activity of compound 5 was evaluated against gastric (EPG85 257) and pancreatic (EPP85-181) human cancer cells and their drug-selected counterparts (EPG85-257RDB, EPG85-257RNOV, EPP85-181RDB, EPP85-181RNOV). The drug induced cell death was investigated for compounds 4 and 5, using the annexin V/PI staining and the active caspase-3 assay. RESULTS: The jatrophanes 1-5 were able to modulate the efflux activity of ABCB1, and at 2uM, 3-5 maintained the strong modulator profile. Structure activity results indicated that high conformational flexibility of the twelve-membered ring of compounds 3-5 favored ABCB1 modulation, in contrast to the tetracyclic scaffold of compounds 1 and 2. The effects of epoxywelwitschene (4) on the ATPase activity of ABCB1 showed it to interact with the transporter and to be able to reduce the transport of a second subtrate. Drug combination experiments also corroborated the anti-MDR potential of these diterpenes due to their synergistic interaction with doxorubicin (combination index <0.7). Esulatin M (5) showed a strong MDR-selective antiproliferative activity against EPG85-257RDB and EPP85-181RDB cells, with IC50 of 1.8 and 4.8 uM, respectively. Compounds 4 and 5 induced apoptosis via caspase 3 activation. A significant discrimination was observed between the resistant cell lines and parental cells. CONCLUSIONS: This study strengthens the role of jatrophane diterpenes as lead candidates for the development of MDR reversal agents, higlighting the action of compounds 4 and 5. PMID- 27387406 TI - Reply. PMID- 27387407 TI - Reply. PMID- 27387408 TI - Evaluation of the effect of some additives on the efficiency of binder liquid in wet agglomeration of crystals. AB - OBJECTIVE: Wet agglomeration is a process wherein dispersed particles are held together in an aggregated form by the presence of a small quantity of solvent which acts as binder liquid. In this work, the efficiency of binder liquid was tested in the presence of various additives. METHODS: Solid state of carbamazepine (CBZ) agglomerates was characterized by DSC and FT-IR. The obtained agglomerates were also investigated in terms of yield, size distribution, friability, and drug release. RESULTS: CBZ agglomerates formed only in the presence of talc, span, and croscarmellose sodium (CCS), whereas ethyl cellulose and eudragit RS100 failed to make CBZ agglomerates. The presence of talc decreased the agglomerate size and produced CBZ agglomerates with a poor strength. However, span and CCS led to larger agglomerates with superior strength. In contrast to CCS samples, span and talc altered the dissolution rate of CBZ. FT-IR results showed that there is an interaction between CCS and drug. CONCLUSION: This study suggests that care must be taken when additives are used to manufacture agglomerates as the type of additives even in low concentrations can have a big impact on the efficiency of the binder liquid in forming agglomerates thereby affecting the quality of agglomerates. PMID- 27387409 TI - The component leaching from decellularized pericardial bioscaffolds and its implication in the macrophage response. AB - The extracellular matrix molecules remaining in bioscaffolds derived from decellularized xenogeneic tissues appear to be important for inducing cell functions conducting tissue regeneration. Here, we studied whether decellularization methods, that is, detergent Triton X-100 (TX) alone and TX combined with reversible alkaline swelling (STX), applied to bovine pericardial tissue, could affect the bioscaffold components. The in vitro macrophage response, subdermal biodegradation, and cell infiltration were also studied. The results indicate a lower leaching of fibronectin, but a higher leaching of laminin and sulfated glycosaminoglycans from tissues decellularized with STX and TX, respectively. The in vitro secretion of interleukin-6 and monocyte chemoattractant protein by RAW264.7 macrophages is promoted by decellularized bioscaffold leachates. A lower polymorphonuclear cell density is observed around decellularized bioscaffolds at 1-day implantation; concurrently showing a higher cell infiltration in STX- than in TX-implant. Cells infiltrated into TX-implant show a fibroblastic morphology at 7-day implantation, concurrently the capillary formation is observed at 14-day. Pericardial bioscaffolds suffer biodegradation more pronounced in STX- than in TX-implant. Both TX and STX decellularization methods favor a high leaching of basal lamina components, which presumably promotes a faster macrophage stimulation compared to nondecellularized tissue, and appear to be associated with an increased host cell infiltration in a rat subdermal implantation. Meanwhile, the connective tissue components leaching from TX decellularized bioscaffolds, unlike the STX ones, appear to be associated with an enhanced angiogenesis accompanied by an early-promoted fibroblastic cell transition. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2810-2822, 2016. PMID- 27387410 TI - Inadvertently transected left superior pulmonary vein during thoracoscopic left lower lobectomy. AB - BACKGROUND: There are several anatomical variations of the pulmonary vein which can cause serious complications in pulmonary lobectomy. CASE PRESENTATION: We inadvertently divided the left superior pulmonary vein during thoracoscopic left lower lobectomy in a lung cancer patient. Retrospective review of the preoperative computed tomography showed extra-pericardial common trunk of the left pulmonary venous system. Left superior pulmonary vein was reimplanted into stump of divided common trunk via thoracotomy. CONCLUSIONS: Awareness of vascular anomalies will help thoracic surgeons to prevent potential morbidity and mortality from complications. PMID- 27387411 TI - Erratum. PMID- 27387412 TI - Alphavirus protease inhibitors from natural sources: A homology modeling and molecular docking investigation. AB - Alphaviruses such as Chikungunya virus (CHIKV), O'Nyong-Nyong virus (ONNV), Ross River virus (RRV), Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and Western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that can cause fevers, rash, and rheumatic diseases (CHIKV, ONNV, RRV) or potentially fatal encephalitis (EEEV, VEEV, WEEV) in humans. These diseases are considered neglected tropical diseases for which there are no current antiviral therapies or vaccines available. The alphavirus non structural protein 2 (nsP2) contains a papain-like protease, which is considered to be a promising target for antiviral drug discovery. In this work, molecular docking analyses have been carried out on a library of 2174 plant-derived natural products (290 alkaloids, 664 terpenoids, 1060 polyphenolics, and 160 miscellaneous phytochemicals) with the nsP2 proteases of CHIKV, ONNV, RRV, EEEV, VEEV, WEEV, as well as Aura virus (AURV), Barmah Forest Virus (BFV), Semliki Forest virus (SFV), and Sindbis virus (SINV) in order to identity structural scaffolds for inhibitor design or discovery. Of the 2174 phytochemicals examined, a total of 127 showed promising docking affinities and poses to one or more of the nsP2 proteases, and this knowledge can be used to guide experimental investigation of potential inhibitors. PMID- 27387413 TI - Effect of crude glycerol impurities on lipid preparation by Rhodosporidium toruloides yeast 32489. AB - Crude glycerol (byproduct of biodiesel preparation) was utilised as the carbon source to produce lipid using oleaginous yeast Rhodosporidium toruloides 32489. Under the same conditions, lipid production with crude glycerol was higher than those produced with glucose and pure glycerol. The effects of 4 main impurities in crude glycerol (methyl oleate, sodium oleate, NaCl and methanol) on lipid production were investigated. Compared with utilising pure glycerol, addition of methyl oleate, sodium oleate, and NaCl impurities increased lipid production by 47.0%, 68.0% and 64.0%, respectively, while methanol decreased lipid production by 17.7%. However, when methanol was mixed with other impurities, its inhibition effect was alleviated due to the promoting effect of other impurities. Hence, crude glycerol could be used as a renewable and low-cost carbon source to replace pure glucose or glycerol for lipid preparation. PMID- 27387414 TI - In situ detoxification of dry dilute acid pretreated corn stover by co-culture of xylose-utilizing and inhibitor-tolerant Saccharomyces cerevisiae increases ethanol production. AB - Co-culture of xylose-utilizing and inhibitor-tolerant Saccharomyces cerevisiae was developed for bioethanol production from undetoxified pretreated biomass in simultaneously saccharification and co-fermentation (SSCF) process. Glucose accumulation during late fermentation phase in SSCF using xylose-utilizing strain can be eliminated by the introduction of inhibitor-tolerant strain. Effect of different ratios of two strains was investigated and xylose-utilizing strain to inhibitor-tolerant strain ratio of 10:1 (w/w) showed the best xylose consumption and the highest ethanol yield. Inoculating of xylose-utilizing strain at the later stage of SSCF (24-48h) exhibited lower ethanol yield than inoculating at early stage (the beginning 0-12h), probably due to the reduced enzymatic efficiency caused by the unconsumed xylose and oligomeric sugars. Co-culture SSCF increased ethanol concentration by 21.2% and 41.0% comparing to SSCF using individual inhibitor-tolerant and xylose-utilizing strain (increased from 48.5 and 41.7g/L to 58.8g/L), respectively, which suggest this co-culture system was very promising. PMID- 27387415 TI - Multiple heavy metal removal using an entomopathogenic fungi Beauveria bassiana. AB - Towards the development of a potential remediation technology for multiple heavy metals [Zn(II), Cu(II), Cd(II), Cr(VI) and Ni(II)] from contaminated water, present study examined the growth kinetics and heavy metal removal ability of Beauveria bassiana in individual and multi metals. The specific growth rate of B. bassiana varied from 0.025h(-1) to 0.039h(-1) in presence of individual/multi heavy metals. FTIR analysis indicated the involvement of different surface functional groups in biosorption of different metals, while cellular changes in fungus was reflected by various microscopic (SEM, AFM and TEM) analysis. TEM studies proved removal of heavy metals via sorption and accumulation processes, whereas AFM studies revealed increase in cell surface roughness in fungal cells exposed to heavy metals. Present study delivers first report on the mechanism of bioremediation of heavy metals when present individually as well as multi metal mixture by entomopathogenic fungi. PMID- 27387416 TI - Objective drivers of subjective well-being in geriatric inpatients: mobility function and level of education are general predictors of self-evaluated health, feeling of loneliness, and severity of depression symptoms. AB - PURPOSE: Identification of optimal predictors for different indicators of subjective well-being (SWB) in geriatric inpatients: (1) self-evaluated health status (SEH), (2) feeling of loneliness (FoL), and (3) severity of depression symptoms (SoDS). Investigation of the relationship between response categories of the SWB indicators and their predictors. METHODS: The data were collected retrospectively from hospital records. All 555 geriatric inpatients underwent a comprehensive geriatric assessment, including the Timed Up and Go (TUG) test. The Bayesian information criterion was applied in ordinal logistic regression models to identify optimal predictors of SEH, FoL, and SoDS among different objective factors. RESULTS: After controlling for high-stress situations in the recent past, motor slowness measured with the TUG test, and a level of education were jointly selected as the best predictors of all three SWB indicators. The speed of performing the TUG test improved SEH (OR = 2.08) and decreased both FoL (OR = 0.41) and SoDS (OR = 0.41). A higher level of education improved SEH (OR = 1.05) and alleviated both FoL (OR = 0.96) and SoDS (OR = 0.92). Additionally, a higher level of SEH was positively correlated with a lower BMI, improved instrumental activities of daily living (I-ADL), and higher hemoglobin level. FoL was reinforced by the level of comorbidity, and SoDS was increased by impaired basic ADL. CONCLUSION: Although SWB in geriatric inpatients can be explained by objective comorbidities and disabilities, the good motor function (i.e., a TUG test outcome of less than about 20 s) and a higher level of education were the general predictors that exert an independent beneficial impact on all three SWB indicators. PMID- 27387417 TI - Measurement of utility in asthma: evidence indicating that generic instruments may miss clinically important changes. AB - BACKGROUND: Accurate assessment of preference-based health-related quality of life is important in determining the value of asthma interventions. OBJECTIVE: To examine the sensitivity and responsiveness of the EQ-5D and the AQL-5D to differences in asthma control measured by the Asthma Control Questionnaire (ACQ 5). METHODS: The Observational Study of Asthma Control and Outcomes was a prospective survey of persistent asthma patients >=12 years old in Kaiser Colorado. Patients received a survey three times in 1 year, including the ACQ-5, AQL-5D and EQ-5D-3L (including VAS). Censored Least Absolute Deviations (CLAD) and logistic regression were used, controlling for sociodemographics and smoking. RESULTS: There were 6666 completed surveys (1799 individuals completed all three survey waves). After controlling for covariates, each one-point increase in ACQ-5 was associated with a decrease of 0.066, 0.058, 0.074 and 6.12 in EQ-5D(US), EQ 5D(UK), AQL-5D and VAS scores. Uncontrolled asthma (ACQ-5 > 1.5) was associated with a decrease of 0.15, 0.17, 0.11 and 10, respectively (vs. ACQ <= 1.5). AQL-5D scores were statistically significantly different across categories of ACQ-5 scores of 0.5 (the minimum clinically important difference [MCID]), while EQ-5D scores were not significant across most categories. The AQL-5D appeared more robust to changes in control over time (responsiveness) compared to EQ-5D-3L. CONCLUSION: The AQL-5D appears more responsive to changes in asthma control over time and more sensitive to detecting differences corresponding to the ACQ-5 MCID than the EQ-5D-3L. Using the EQ-5D-3L without an asthma-specific measure such as the AQL-5D may miss clinically important changes in asthma control. PMID- 27387418 TI - Planar modes free piezoelectric resonators using a phononic crystal with holes. AB - By using the principles behind phononic crystals, a periodic array of circular holes made along the polarization thickness direction of piezoceramic resonators are used to stop the planar resonances around the thickness mode band. In this way, a piezoceramic resonator adequate for operation in the thickness mode with an in phase vibration surface is obtained, independently of its lateral shape. Laser vibrometry, electric impedance tests and finite element models are used to corroborate the performances of different resonators made with this procedure. This method can be useful in power ultrasonic devices, physiotherapy and other external medical power ultrasound applications where piston-like vibration in a narrow band is required. PMID- 27387419 TI - Metabolic engineering of Agrobacterium sp. ATCC31749 for curdlan production from cellobiose. AB - Curdlan is a commercial polysaccharide made by fermentation of Agrobacterium sp. Its anticipated expansion to larger volume markets demands improvement in its production efficiency. Metabolic engineering for strain improvement has so far been limited due to the lack of genetic tools. This research aimed to identify strong promoters and to engineer a strain that converts cellobiose efficiently to curdlan. Three strong promoters were identified and were used to install an energy-efficient cellobiose phosphorolysis mechanism in a curdlan-producing strain. The engineered strains were shown with enhanced ability to utilize cellobiose, resulting in a 2.5-fold increase in titer. The availability of metabolically engineered strain capable of producing beta-glucan from cellobiose paves the way for its production from cellulose. The identified native promoters from Agrobacterium open up opportunities for further metabolic engineering for improved production of curdlan and other products. The success shown here marks the first such metabolic engineering effort in this microbe. PMID- 27387421 TI - Discovery and antiplatelet activity of a selective PI3Kbeta inhibitor (MIPS 9922). AB - A series of amino-substituted triazines were developed and examined for PI3Kbeta inhibition and anti-platelet function. Structural adaptations of a morpholine ring of the prototype pan-PI3K inhibitor ZSTK474 yielded PI3Kbeta selective compounds, where the selectivity largely derives from an interaction with the non conserved Asp862 residue, as shown by site directed mutagenesis. The most PI3Kbeta selective inhibitor from the series was studied in detail through a series of in vitro and in vivo functional studies. MIPS-9922, 10 potently inhibited ADP-induced washed platelet aggregation. It also inhibited integrin alphaIIbbeta3 activation and alphaIIbbeta3 dependent platelet adhesion to immobilized vWF under high shear. It prevented arterial thrombus formation in the in vivo electrolytic mouse model of thrombosis without inducing prolonged bleeding or excess blood loss. PMID- 27387420 TI - FGF21 ameliorates the neurocontrol of blood pressure in the high fructose drinking rats. AB - Fibroblast growth factor-21 (FGF21) is closely related to various metabolic and cardiovascular disorders. However, the direct targets and mechanisms linking FGF21 to blood pressure control and hypertension are still elusive. Here we demonstrated a novel regulatory function of FGF21 in the baroreflex afferent pathway (the nucleus tractus solitarii, NTS; nodose ganglion, NG). As the critical co-receptor of FGF21, beta-klotho (klb) significantly expressed on the NTS and NG. Furthermore, we evaluated the beneficial effects of chronic intraperitoneal infusion of recombinant human FGF21 (rhFGF21) on the dysregulated systolic blood pressure, cardiac parameters, baroreflex sensitivity (BRS) and hyperinsulinemia in the high fructose-drinking (HFD) rats. The BRS up-regulation is associated with Akt-eNOS-NO signaling activation in the NTS and NG induced by acute intravenous rhFGF21 administration in HFD and control rats. Moreover, the expressions of FGF21 receptors were aberrantly down-regulated in HFD rats. In addition, the up-regulated peroxisome proliferator-activated receptor-gamma and alpha (PPAR-gamma/-alpha) in the NTS and NG in HFD rats were markedly reversed by chronic rhFGF21 infusion. Our study extends the work of the FGF21 actions on the neurocontrol of blood pressure regulations through baroreflex afferent pathway in HFD rats. PMID- 27387423 TI - Pristine Graphene Aerogels by Room-Temperature Freeze Gelation. AB - Aerogels can be fabricated from pristine graphene exfoliated nanosheets using freeze gelation with nonaqueous solvents and no heat treatment or reduction stage. Solvents are selected that disperse pristine graphene with a melting point above room temperature but with a high vapor pressure above the solid at room temperature, enabling sublimation (freeze drying) under ambient conditions. PMID- 27387422 TI - Reduction in Acute Respiratory Infection Among Military Trainees: Secondary Effects of a Hygiene-Based Cluster-Randomized Trial for Skin and Soft-Tissue Infection Prevention. PMID- 27387424 TI - Sex difference in attractiveness perceptions of strong and weak male walkers. AB - OBJECTIVES: Men and women accurately assess male physical strength from facial and body morphology cues. Women's assessments of male facial attractiveness, masculinity, and dominance correlate positively with male physical strength. A positive relationship also has been reported between physical strength and attractiveness of men's dance movements. Here, we investigate men's and women's attractiveness, dominance, and strength assessments from brief samples of male gait. METHODS: Handgrip strength (HGS) was measured in 70 heterosexual men and their gait was motion-captured. Men and women judged 20 precategorized strong (high HGS) and weak (low HGS) walkers on attractiveness, dominance, and strength, and provided a measure of their own HGS. RESULTS: Both men and women judged strong walkers higher on dominance and strength than weak walkers. Women but not men judged strong walkers more attractive than weak walkers. These effects were independent of observers' physical strength. CONCLUSIONS: Male physical strength is conveyed not only through facial and body morphology, but also through body movements. We discuss our findings with reference to studies suggesting that physical strength provides information about male quality in contexts of inter- and intrasexual selection. Am. J. Hum. Biol. 28:913-917, 2016. (c) 2016Wiley Periodicals, Inc. PMID- 27387425 TI - Impaired maturation of distal radio-cephalic fistula for haemodialysis: a review of treatment options. AB - Distal radio-cephalic arteriovenous fistula is the 'gold standard' vascular access for chronic hemodialysis. Its main drawback is early failure, which can complicate up to 50 % of this surgical procedure. Two scenarios of failure are possible: early post-operative thrombosis or impaired maturation. The first is mainly due to a defective preoperative evaluation or poor surgical procedure. The latter is a patent angioaccess unable to deliver adequately hemodialysis due to a persistently low blood flow or difficult cannulation. In this article, the causes of impaired maturation will be reviewed, ranging from the stenosis causing low flow to the deep location of the vein in the obese. Treatment options will be described in thorough technical detail, in order to allow the angioaccess team to master them in daily practice. PMID- 27387427 TI - [Not Available]. PMID- 27387426 TI - Urinary retinol-binding protein as a risk factor of poor prognosis in acute-on chronic renal injury. AB - BACKGROUND: Acute-on-chronic renal injury was commonly seen in clinical practice. Reversibility of acute-on-chronic renal injury had not yet been carefully explored. This study tested whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal injury. METHODS: 108 adult patients with pre-existing chronic kidney disease presenting with acute-on-chronic renal injury were included. Urinary retinol-binding protein (uRBP), N-Acetyl-b-D-Glucosaminidase (uNAG) and albumin (uALB) was quantified. RESULTS: Reversibility of renal function was achieved in 43 patients of the 108 included patients. The levels of urinary retinol-binding protein, N-Acetyl-b-D Glucosaminidase and albumin for non-recovery acute-on-chronic renal injury patients were much higher than recovery patients. The fourth quartiles of urinary retinol-binding protein were significantly associated with at least 1.055-fold odds of non-recovery and the urinary retinol-binding protein was an independent risk factor for outcome of acute-on-chronic renal injury patients by multivariate logistic regression analysis. Quartiles of both urinary N-Acetyl-b-D Glucosaminidase and albumin had a graded relationship with the risk for un recovery AKI. However, after a multivariate logistic analysis, the urinary N Acetyl-b-D-Glucosaminidase and albumin was not associated with reversibility of acute-on-chronic renal injury. CONCLUSION: In patients with acute-on-chronic renal injury, urinary retinol-binding protein was associated with the reversibility of kidney function. Quantification of urinary retinol-binding protein may be developed as a non-invasive tool for predicting outcome of acute on-chronic renal injury patients. PMID- 27387428 TI - Influenza pathogenicity during pregnancy in women and animal models. AB - Pregnant women are at the highest risk to develop severe and even fatal influenza. The high vulnerability of women against influenza A virus infections during pregnancy was repeatedly highlighted during influenza pandemics including the pandemic of this century. In 2009, mortality rates were particularly high among otherwise healthy pregnant women. However, our current understanding of the molecular mechanisms involved in severe disease development during pregnancy is still very limited. In this review, we summarize the knowledge on the clinical observations in influenza A virus-infected pregnant women. In addition, knowledge obtained from few existing experimental infections in pregnant animal models is discussed. Since clinical data do not provide in-depth information on the pathogenesis of severe influenza during pregnancy, adequate animal models are urgently required that mimic clinical findings. Studies in pregnant animal models will allow the dissection of involved molecular disease pathways that are key to improve patient management and care. PMID- 27387429 TI - A functional splice variant of the human Golgi CMP-sialic acid transporter. AB - The human Golgi Cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Sia) transporter SLC35A1, a member of the nucleotide sugar transporter family, translocates CMP-Sia from the cytosol into the Golgi lumen where sialyltransferases use it as donor substrate for the synthesis of sialoglycoconjugates. In 2005, we reported a novel Congenital Disorder of Glycosylation (CDG) termed CDG-IIf or SLC35A1-CDG, characterized by macrothrombocytopenia, neutropenia and complete lack of the sialyl-Lex antigen (NeuAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc-R) on polymorphonuclear cells. This disease was caused by the presence of inactive SLC35A1 alleles. It was also found that the SLC35A1 generates additional isoforms through alternative splicing. In this work, we demonstrate that one of the reported isoforms, the del177 with exon 6 skipping, is able to maintain sialylation in HepG2 cells submitted to wt knockdown and restore sialylation to normal levels in the Chinese Hamester Ovary (CHO) cell line Lec2 mutant deficient in CMP-Sia transport. The characteristics of the alternatively spliced protein are discussed as well as therapeutic implications of this finding in CDGs caused by mutations in nucleotide sugar transporters (NSTs). PMID- 27387431 TI - Three-dimensional nanotubes composed of carbon-anchored ultrathin MoS2 nanosheets with enhanced lithium storage. AB - MoS2 nanotubes (denoted as MoS2 NTs) assembled from well-aligned amorphous carbon modified ultrathin MoS2 nanosheets (denoted as MoS2 NT@C) were successfully fabricated via a facile solvothermal method combined with subsequent annealing treatment. With the assistance of octylamine as a solvent and carbon source, interconnected MoS2 nanosheets (denoted as MoS2 NSs) can assemble into hierarchical MoS2 NTs. Such a hybrid nanostructure can effectively facilitate charge transport and accommodate volume variation upon prolonged charge/discharge cycling for reversible lithium storage. As a result, the MoS2 NT@C composite manifests a very stable high reversible capacity of around 1351 mA h g(-1) at a current density of 100 mA g(-1); even after 150 cycles, the electrode reaches a capacity of 1106 mA h g(-1) and it retains a reversible capacity of 650 mA h g( 1) after the 10th cycle at a current density of 3 A g(-1), all of which indicate that the MoS2 NT@C nanocomposite is a promising negative electrode material for high-energy lithium ion batteries. PMID- 27387430 TI - Unveiling of miRNA Expression Patterns in Purkinje Cells During Development. AB - MicroRNAs (miRNAs) are short noncoding RNAs of 19-25 nucleotides in length that regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs is associated with many disorders and neurodegenerative diseases affecting numerous different pathways and processes, of which many have not yet been completely explored. Recent studies even indicate a crucial role of miRNAs during brain development, with differential expression patterns of several miRNAs seen in both developing and mature cells. A miRNA profiling in brain tissue and the fundamental understanding of their effects might optimize the therapeutical treatment of various neurological disorders. In this study, we performed miRNA array analysis of enriched cerebellar Purkinje cell (PC) samples from both young and mature rat cerebella. We used laser microdissection (LMD) to enrich PC for a highly specific miRNA profiling. Altogether, we present the expression profile of at least 27 miRNAs expressed in rat cerebellar PC and disclose a different expression pattern of at least three of these miRNAs during development. These miRNAs are potential candidates for the regulation and control of cerebellar PC development, including neuritic and dendritic outgrowth as well as spine formation. PMID- 27387432 TI - Predictive ability of urinary biomarkers for outcome in children with acute kidney injury. AB - BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. METHODS: Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. RESULTS: Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls (p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL (p = 0.008) and NAG (p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580 0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75 % each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5 % and specificity 70.8 %, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. CONCLUSIONS: Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay. PMID- 27387433 TI - Should charge variants of monoclonal antibody therapeutics be considered critical quality attributes? AB - Charge variants, namely acidic and basic variants, are typically found in mAb therapeutics. Charge heterogeneity is typically not regarded to affect safety and efficacy of the product. As a result, the commonly followed approach involves assignment of a specification for the variants based on statistical analysis of variability in levels that is seen during commercial manufacturing. This is followed by monitoring of product quality to demonstrate consistency. This paper aims to demonstrate that this perception of charge variants warrants a more in depth investigation to evaluate the role charge variants play in safety and efficacy of a mAb therapeutic. In addition, a novel procedure has been suggested for making this assessment and alleviate the problems that are traditionally faced when isolating these variants for characterization. The suggested procedure utilizes the principles of bioseparations, cell biology, and statistics and it is demonstrated that this is significantly more efficient than the approach practiced today. PMID- 27387434 TI - Development and validation of the Italian version of the Mobile Application Rating Scale and its generalisability to apps targeting primary prevention. AB - BACKGROUND: A growing body of literature affirms the usefulness of mobile technologies, including mobile applications (apps), in the primary prevention field. The quality of health apps, which today number in the thousands, is a crucial parameter, as it may affect health-related decision-making and outcomes among app end-users. The mobile application rating scale (MARS) has recently been developed to evaluate the quality of such apps, and has shown good psychometric properties. Since there is no standardised tool for assessing the apps available in Italian app stores, the present study developed and validated an Italian version of MARS in apps targeting primary prevention. METHODS: The original 23 item version of the MARS assesses mobile app quality in four objective quality dimensions (engagement, functionality, aesthetics, information) and one subjective dimension. Validation of this tool involved several steps; the universalist approach to achieving equivalence was adopted. Following two backward translations, a reconciled Italian version of MARS was produced and compared with the original scale. On the basis of sample size estimation, 48 apps from three major app stores were downloaded; the first 5 were used for piloting, while the remaining 43 were used in the main study in order to assess the psychometric properties of the scale. The apps were assessed by two raters, each working independently. The psychometric properties of the final version of the scale was assessed including the inter-rater reliability, internal consistency, convergent, divergent and concurrent validities. RESULTS: The intralingual equivalence of the Italian version of the MARS was confirmed by the authors of the original scale. A total of 43 apps targeting primary prevention were tested. The MARS displayed acceptable psychometric properties. The MARS total score showed an excellent level of both inter-rater agreement (intra-class correlation coefficient of .96) and internal consistency (Cronbach's alpha of .90 and .91 for the two raters, respectively). Other types of validity, including convergent, divergent, discriminative, known-groups and scalability, were also established. CONCLUSIONS: The Italian version of MARS is a valid and reliable tool for assessing the health-related primary prevention apps available in Italian app stores. PMID- 27387435 TI - Effects of Water on Structure and Dynamics of Trehalose Glasses at Low Water Contents and its Relationship to Preservation Outcomes. AB - Dry preservation of biologics in sugar glasses is regarded as a promising alternative to conventional cryopreservation. Evidence from various studies has suggested that there is a critical range of water content beyond which the viability of preserved biologics can be greatly compromised. In this study the viability of T-cells was determined as a function of end water content after microwave-assisted drying in trehalose solutions. Hydrogen-bonding and clustering phenomena in trehalose solutions of the same moisture content were also evaluated using molecular dynamics simulation. Post-rehydration viability decreased dramatically within the range of 0.1-1 gH2O/gdw. Molecular modeling revealed that as the water content approached 0.1 gH2O/gdw the matrix formed a large interconnected trehalose skeleton with a minimal number of bound water molecules scattered in the bulk. The diffusion coefficients of trehalose oxygen atoms most distant from the glycosidic linkage fluctuated around 7.5 * 10(-14) m(2)/s within the range of 0.02-0.1 gH2O/gdw and increased again to ~1.13 * 10(-13) m(2)/s at 0.01 gH2O/gdw and below due to the loss of water in the free volume between trehalose molecules. These insights can guide the optimal selection of final moisture contents to advance dry preservation methods. PMID- 27387436 TI - Molecular and Electronic Structure of Re2Br4(PMe3)4. AB - The dinuclear rhenium(II) complex Re2Br4(PMe3)4 was prepared from the reduction of [Re2Br8](2-) with (n-Bu4N)BH4 in the presence of PMe3 in propanol. The complex was characterized by single-crystal X-ray diffraction (SCXRD) and UV-visible spectroscopy. It crystallizes in the monoclinic C2/c space group and is isostructural with its molybdenum and technetium analogues. The Re-Re distance (2.2521(3) A) is slightly longer than the one in Re2Cl4(PMe3)4 (2.247(1) A). The molecular and electronic structure of Re2X4(PMe3)4 (X = Cl, Br) were studied by multiconfigurational quantum chemical methods. The computed ground-state geometry is in excellent agreement with the experimental structure determined by SCXRD. The calculated total bond order (2.75) is consistent with the presence of an electron-rich triple bond and is similar to the one found for Re2Cl4(PMe3)4. The electronic absorption spectrum of Re2Br4(PMe3)4 was recorded in benzene and shows a series of low-intensity bands in the range 10 000-26 000 cm(-1). The absorption bands were assigned based on calculations of the excitation energies with the multireference wave functions followed by second-order perturbation theory using the CASSCF/CASPT2 method. Calculations predict that the lowest energy band corresponds to the delta* -> sigma* transition, while the next higher energy bands were attributed to the delta* -> pi*, delta -> sigma*, and delta -> pi* transitions. PMID- 27387437 TI - Detection, prevalence, and transmission of avian hematozoa in waterfowl at the Arctic/sub-Arctic interface: co-infections, viral interactions, and sources of variation. AB - BACKGROUND: The epidemiology of avian hematozoa at high latitudes is still not well understood, particularly in sub-Arctic and Arctic habitats, where information is limited regarding seasonality and range of transmission, co infection dynamics with parasitic and viral agents, and possible fitness consequences of infection. Such information is important as climate warming may lead to northward expansion of hematozoa with unknown consequences to northern breeding avian taxa, particularly populations that may be previously unexposed to blood parasites. METHODS: We used molecular methods to screen blood samples and cloacal/oropharyngeal swabs collected from 1347 ducks of five species during May August 2010, in interior Alaska, for the presence of hematozoa, Influenza A Virus (IAV), and IAV antibodies. Using models to account for imperfect detection of parasites, we estimated seasonal variation in prevalence of three parasite genera (Haemoproteus, Plasmodium, Leucocytozoon) and investigated how co-infection with parasites and viruses were related to the probability of infection. RESULTS: We detected parasites from each hematozoan genus in adult and juvenile ducks of all species sampled. Seasonal patterns in detection and prevalence varied by parasite genus and species, age, and sex of duck hosts. The probabilities of infection for Haemoproteus and Leucocytozoon parasites were strongly positively correlated, but hematozoa infection was not correlated with IAV infection or serostatus. The probability of Haemoproteus infection was negatively related to body condition in juvenile ducks; relationships between Leucocytozoon infection and body condition varied among host species. CONCLUSIONS: We present prevalence estimates for Haemoproteus, Leucocytozoon, and Plasmodium infections in waterfowl at the interface of the sub-Arctic and Arctic and provide evidence for local transmission of all three parasite genera. Variation in prevalence and molecular detection of hematozoa parasites in wild ducks is influenced by seasonal timing and a number of host traits. A positive correlation in co-infection of Leucocytozoon and Haemoproteus suggests that infection probability by parasites in one or both genera is enhanced by infection with the other, or that encounter rates of hosts and genus-specific vectors are correlated. Using size-adjusted mass as an index of host condition, we did not find evidence for strong deleterious consequences of hematozoa infection in wild ducks. PMID- 27387438 TI - Manipulating one-way space wave and its refraction by time-reversal and parity symmetry breaking. AB - One-way transmission and negative refraction are the exotic wave properties founded in photonic crystals which attract a great attention due to their promising applications in photonic devices. How to integrate such two phenomena in one material or device is interesting and valuable. In this work, we theoretically and experimentally demonstrate that one-way electromagnetic space wave can be realized by means of two-dimensional magnetic photonic crystals. Simultaneously breaking the time-reversal and parity symmetries of the magnetic photonic crystals designed, we observe oblique incident space wave propagating one-way in the magnetic photonic crystals with positive or negative refraction occurring at interfaces, which can be manipulated upon the incident angle and operating frequency. Our work may offer a potential platform to realize some exotic photoelectronic and microwave devices such as one-way imaging and one-way cloaking. PMID- 27387439 TI - In vitro topological loading of bacterial condensin MukB on DNA, preferentially single-stranded DNA rather than double-stranded DNA. AB - Condensin is the major driving force in the segregation of daughter chromosomes in prokaryotes. Core subunits of condensin belong to the SMC protein family, whose members are characterized by a unique ATPase activity and dimers with a V shaped structure. The V-shaped dimers might close between head domains, forming a ring structure that can encircle DNA. Indeed, cohesin, which is a subfamily of SMC proteins, encircles double-stranded DNA to hold sister chromatids in eukaryotes. However, the question of whether or not condensin encircles the chromosomal DNA remains highly controversial. Here we report that MukB binds topologically to DNA in vitro, and this binding is preferentially single-stranded DNA (ssDNA) rather than double-stranded DNA. The binding of MukB to ssDNA does not require ATP. In fact, thermal energy enhances the binding. The non-SMC subunits MukF and MukE did stimulate the topological binding of MukB, although they hindered DNA-binding of MukB. Recent reports on the distribution of condensin in genomes reveal that actively transcribed genes in yeast and humans are enriched in condensin. In consideration of all these results, we propose that the binding specificity of condensin to chromosome is provided not by the DNA sequence but by the DNA structure, which is ssDNA. PMID- 27387440 TI - Facile growth of well-dispersed and ultra-small MoS2 nanodots in ordered mesoporous silica nanoparticles. AB - A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (~1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs). PMID- 27387441 TI - Intra-patient comparison of parietal pleural biopsies by rigid forceps, flexible forceps and cryoprobe obtained during medical thoracoscopy: a prospective series of 80 cases with pleural effusion. AB - BACKGROUND: There is only few data available on the use of cryotechnique during medical thoracoscopy. METHODS: Medical thoracoscopy was performed in consecutive patients with pleural effusion. Prospectively, biopsies were taken by rigid forceps, flexible forceps and cryoprobe. Specimen size, depth and diagnostic yield were compared. RESULTS: 80 Patients were included. 408 biopsies were taken (205 rigid biopsies, 104 flexible biopsies, 99 cryobiopsies). Mean surface area of rigid biopsies was 22.6 +/- 20.4 mm(2) (flexible biopsies: 7.1 +/- 9.3 mm(2), cryobiopsies: 14.4 +/- 12.8 mm(2)). Rigid biopsies were significantly larger than cryobiopsies (p < 0.001) and flexible biopsies (p < 0.001), crybiopsies were significantly larger than flexible biopsies (p < 0.01). A deep biopsy containing fatty tissue was harvested in 63 % of rigid biopsies (cryobiopsy: 49.5 % flexible biopsy: 39.5 %). In 79/80 cases (98.7 % 95 % CI cannot be calculated) a diagnosis was obtained by rigid biopsy (cryobiopsy: 73/80 cases (91.3 % 95 % CI 86.0 - 96.5 %), flexible biopsy: 74/80 cases (92.5 % 95 % CI 88.6 - 97.4 %)). Diagnostic yield achieved with cryobiopsies was inferior to the yield of rigid biopsies (Difference: 12.7 %), but non-inferior to flexible biopsies (Difference: 6.5 %). CONCLUSION: Cryobiopsies in medical thoracoscopy are safe with high diagnostic yield, non-inferior to flexible biopsies with increased tissue quantity and quality. Cryotechnique can develop an important role in medical thoracoscopy in the near future when rigid thoracoscopy is not available. PMID- 27387442 TI - Effects of random food deprivation and refeeding on energy metabolism, behavior and hypothalamic neuropeptide expression in Apodemus chevrieri. AB - Maintaining adaptive control of behavior and physiology is the main strategy used by animals in responding to changes of food resources. To investigate the effects of random food deprivation (FD) and refeeding on energy metabolism and behavior in Apodemus chevrieri, we acclimated adult males to FD for 4weeks, then refed them ad libitum for 4weeks (FD-Re group). During the period of FD, animals were fed ad libitum for 4 randomly assigned days each week, and deprived of food the other 3days. A control group was fed ad libitum for 8weeks. At 4 and 8weeks we measured body mass, thermogenesis, serum leptin levels, body composition, gastrointestinal tract morphology, behavior and hypothalamic neuropeptide expression. At 4weeks, food intake, gastrointestinal mass, neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expressions increased and thermogenesis, leptin levels, pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) expressions decreased in FD compared with controls. FD also showed more resting behavior and less activity than the controls on ad libitum day. There were no differences between FD-Re and controls at 8weeks, indicating significant plasticity. These results suggested that animals can compensate for unpredictable reduction in food availability by increasing food intake and reducing energy expended through thermogenesis and activity. Leptin levels, NPY, AgRP, POMC, and CART mRNA levels may also regulate energy metabolism. Significant plasticity in energy metabolism and behavior was shown by A. chevrieri over a short timescale, allowing them to adapt to food shortages in nutritionally unpredictable environments. PMID- 27387443 TI - Hypoxia-reoxygenation differentially alters the thermal sensitivity of complex I basal and maximal mitochondrial oxidative capacity. AB - Hypoxia-reoxygenation (H-R) transitions and temperature fluctuations occur frequently in biological systems and likely interact to alter cell function. To test how H-R modulates mitochondrial function at different temperatures we measured the effects of H-R on isolated fish liver mitochondrial oxidation rates over a wide temperature range (5-25 degrees C). Subsequently, the mechanisms underlying H-R induced mitochondrial responses were examined. H-R inhibited the complex I (CI) maximal (state 3) and stimulated the basal (state 4) mitochondrial oxidation rates with temperature enhancing both effects. As a result, the thermal sensitivity (Q10) for CI maximal respiration was reduced while that for basal respiration was increased by H-R. H-R reduced both the coupling and phosphorylation efficiencies more profoundly at high temperature suggesting that mitochondria were more resistant to H-R at low temperature. The H-R induced mitochondrial impairments were associated with increased reactive oxygen species (ROS) production and proton leak, dissipation of membrane potential, and loss of structural integrity of the organelles. Overall, our study provides insight into the mechanisms of H-R induced mitochondrial morphofunctional disruption and shows that the moderation of effects of H-R on oxidative phosphorylation by temperature depends on the functional state. PMID- 27387444 TI - Regulation of sex steroid production and mRNAs encoding gonadotropin receptors and steroidogenic proteins by gonadotropins, cyclic AMP and insulin-like growth factor-I in ovarian follicles of rainbow trout (Oncorhynchus mykiss) at two stages of vitellogenesis. AB - At the completion of vitellogenesis, the steroid biosynthetic pathway in teleost ovarian follicles switches from estradiol-17beta (E2) to maturational progestin production, associated with decreased follicle stimulating hormone (Fsh) and increased luteinizing hormone (Lh) signaling. This study compared effects of gonadotropins, human insulin-like growth factor-I (IGF1), and cAMP/protein kinase A signaling (forskolin) on E2 production and levels of mRNAs encoding steroidogenic proteins and gonadotropin receptors using midvitellogenic (MV) and late/postvitellogenic (L/PV) ovarian follicles of rainbow trout. Fsh, Lh and forskolin, but not IGF1, increased testosterone and E2 production in MV and L/PV follicles. Fsh increased steroidogenic acute regulatory protein (star; MV), 3beta hydroxysteroid dehydrogenase/Delta(5-4) isomerase (hsd3b; MV) and P450 aromatase (cyp19a1a; MV) transcript levels. Lh increased star mRNA levels (MV, L/PV) but reduced cyp19a1a transcripts in L/PV follicles. At both follicle stages, IGF1 reduced levels of hsd3b transcripts. In MV follicles, IGF1 decreased P450 side chain cleavage enzyme (cyp11a1) transcripts but increased cyp19a1a transcripts. In MV follicles only, forskolin increased star and hsd3b transcripts. Forskolin reduced MV follicle cyp11a1 transcripts and reduced cyp19a1a transcripts in follicles at both stages. Fsh and Lh reduced fshr transcripts in L/PV follicles. Lh also reduced lhcgr transcripts (L/PV). IGF1 had no effect on gonadotropin receptor transcripts. Forskolin reduced MV follicle fshr transcript levels and reduced lhcgr transcripts in L/PV follicles. These results reveal hormone- and stage-specific transcriptional regulation of steroidogenic protein and gonadotropin receptor genes and suggest that the steroidogenic shift at the completion of vitellogenesis involves loss of stimulatory effects of Fsh and Igfs on cyp19a1a expression and inhibition of cyp19a1a transcription by Lh. PMID- 27387445 TI - Immune response and innervation signatures in aseptic hip implant loosening. AB - BACKGROUND: Aseptic loosening (AL) of hip prosthesis presents inflammation and pain as sign and symptom similarly to arthritis pathologies. Still, the immune and innervation profiles in hip AL remain unclear and their interplay is poorly explored. Herein, local tissue inflammatory response, sensory and sympathetic innervation as well as associated local mediators were assessed in hip joint microenvironment underlying AL and compared to osteoarthritis (OA). METHODS: Histopathological analysis, immune cells (macrophages, T, B cells and PMNs) as well as sensory and sympathetic nerve fibers (SP(+), CGRP(+), TH(+)) distribution and profiles were analyzed on tissues retrieved from patients with failed hip prostheses due to AL (n = 20) and hip OA (n = 15) by immunohistochemistry. Additionally, transcriptional levels of pro-inflammatory cytokines (TNF-alpha, IL 1beta, IL-6, IL-12a, iNOS), anti-inflammatory cytokine (IL-10), osteoclastic factor (RANKL) and bone remodeling factor (TGF-beta1) were locally evaluated by qRT-PCR. Serum TGF-beta1 levels were assessed preoperatively by ELISA. RESULTS: Histopathological analysis revealed that tissues, aseptic interface membranes of AL patients had distinct tissue architecture and immune cells profile when compared to OA synovial tissues. Macrophages, T cells and B cells showed significant differences in tissue distribution. In OA, inflammation is mostly confined to the vicinity of synovial membrane while in AL macrophages infiltrated throughout the tissue. This differential immune profile is also accompanied with a distinct pattern of sensory and sympathetic innervation. Importantly, in AL patients, a lack of sympathetic innervation aseptic interface membranes without compensation mechanisms at cellular levels was observed with simultaneous reorganization of sensorial innervation. Despite the different histopathological portrait, AL and OA patients exhibited similar transcriptional levels of genes encoding key proteins in local immune response. Nevertheless, in both pathologies, TGF-beta1 expression was prominent in sites where the inflammation is occurring. However, at systemic level no differences were found. CONCLUSION: These findings indicate that AL patients exhibit different local inflammatory response and innervation signatures from OA patients in hip joint. These insights shed the light on neuro-immune interplay in AL and highlight the need to better understand this crosstalk to unravel potential mechanisms for targeted-therapies to improve hip joint lifetime and treatment. PMID- 27387447 TI - A structural equation modeling of executive functions, IQ and mathematical skills in primary students: Differential effects on number production, mental calculus and arithmetical problems. AB - Though the relationship between executive functions (EFs) and mathematical skills has been well documented, little is known about how both EFs and IQ differentially support diverse math domains in primary students. Inconsistency of results may be due to the statistical techniques employed, specifically, if the analysis is conducted with observed variables, i.e., regression analysis, or at the latent level, i.e., structural equation modeling (SEM). The current study explores the contribution of both EFs and IQ in mathematics through an SEM approach. A total of 118 8- to 12-year-olds were administered measures of EFs, crystallized (Gc) and fluid (Gf) intelligence, and math abilities (i.e., number production, mental calculus and arithmetical problem-solving). Confirmatory factor analysis (CFA) offered support for the three-factor solution of EFs: (1) working memory (WM), (2) shifting, and (3) inhibition. Regarding the relationship among EFs, IQ and math abilities, the results of the SEM analysis showed that (i) WM and age predict number production and mental calculus, and (ii) shifting and sex predict arithmetical problem-solving. In all of the SEM models, EFs partially or totally mediated the relationship between IQ, age and math achievement. These results suggest that EFs differentially supports math abilities in primary-school children and is a more significant predictor of math achievement than IQ level. PMID- 27387446 TI - A phase I trial of the trifunctional anti Her2 * anti CD3 antibody ertumaxomab in patients with advanced solid tumors. AB - BACKGROUND: Ertumaxomab (ertu) is a bispecific, trifunctional antibody targeting Her2/neu, CD3 and the Fcgamma-receptors I, IIa, and III forming a tri-cell complex between tumor cell, T cell and accessory cells. METHODS: Patients (pts) with Her2/neu (1+/SISH positive, 2+ and 3+) expressing tumors progressing after standard therapy were treated to investigate safety, tolerability and preliminary efficacy. In this study, ertu was applied i.v. in 2 cycles following a predefined dose escalating scheme. Each cycle consisted of five ascending doses (10-500 MUg) applied weekly within 28 days with a 21 day treatment-free interval. If 2 pts experienced a dose limiting toxicity (DLT) at a given dose level, the maximum tolerated dose (MTD) had been exceeded. RESULTS: Fourteen heavily pretreated pts (e.g. breast, rectal, gastric cancer) were enrolled in the four main cohorts. Three (21 %) pts had to be replaced. Two serious adverse events (SAE) with possible relation to the investigational drug were seen, both fully reversible. A DLT was not detected. Consequently, the MTD could not be determined. All adverse events (AE) were transient and completely reversible. Most frequent AEs were fatigue (14/14), pain (13/14), cephalgia (12/14), chills (11/14), nausea (8/14), fever (7/14), emesis (7/14) and diarrhea (5/14). Single doses up to 300 MUg were well tolerated (total dose up to 800 MUg per cycle). We observed one partial remission and two disease stabilizations after first treatment cycle. CONCLUSIONS: Single doses up to 300 MUg could be safely administered in an escalating dose scheme. Immunological responses and clinical activity warrant further evaluation in patients with Her2 over expressing tumors. TRIAL REGISTRATION: EudraCT number: 2011-003201-14; ClinicalTrials.gov identifier: NCT01569412. PMID- 27387448 TI - Simulation of Molecular Transport in Systems Containing Mobile Obstacles. AB - In this paper, we investigate the movement of molecules in crowded environments with obstacles undergoing Brownian motion by means of extensive Monte Carlo simulations. Our investigations were performed using the dynamic lattice liquid model, which was based on the cooperative movement concept and allowed to mimic systems at high densities where the motion of all elements (obstacles as well as moving particles) were highly correlated. The crowded environments are modeled on a two-dimensional triangular lattice containing obstacles (particles whose mobility was significantly reduced) moving by a Brownian motion. The subdiffusive motion of both elements in the system was analyzed. It was shown that the percolation transition does not exist in such systems in spite of the cooperative character of the particles' motion. The reduction of the obstacle mobility leads to the longer caging of liquid particles by mobile obstacles. PMID- 27387449 TI - Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age. AB - BACKGROUND: We compared demographic and clinical characteristics of early-onset sepsis (EOS) and community-acquired late onset sepsis (CA-LOS) in infants. METHODS: Our medical center is the sole hospital in southern-Israel, enabling incidence calculations. EOS (<7 days) and CA-LOS (7-90 days) episodes recorded between 2007 and 2013 were reviewed. Univariate and multivariate analyses were performed. RESULTS: 70 EOS and 114 CA-LOS episodes were recorded. The respective mean +/- SD annual rates per 1,000 live-births were 0.66 +/- 0.16 and 1.03 +/- 0.23. Prematurity (42.9 % vs. 17.0 %), premature rupture of membranes (PROM; 22.9 % vs. 1.9 %), leukopenia (29.0 % vs. 11.6 %), thrombocytopenia (44.9 % vs. 14.3 %) and Streptococcus agalactiae infections (22.7 % vs. 8.1 %) were more common in EOS. Fever (25.4 % vs. 79.1 %) and Streptococcus pneumoniae infections (1.3 % vs. 12.9 %) were less common in EOS. In both groups, Gram-negative bacteria predominated (~60 %). Longer hospitalization duration (23.3 +/- 25.1 vs. 10.3 +/- 8.6 days) and higher case fatality rate (20.0 % vs. 5.3 %) were noted in EOS. Antibiotic resistance rates to empiric EOS and CA-LOS treatments were 0.0 % and 1.2 %, respectively. In multivariate analysis, adjusting for prematurity and ethnicity, PROM, central line, low Apgar-score, low birth-weight, ventilation support and non-vaginal delivery were risk factors for EOS. Normal temperature, thrombocytopenia and leukopenia characterized EOS. CONCLUSION: EOS and CA-LOS rates were low in Jewish compared with Bedouin infants. EOS was characterized by higher rates of perinatal risk factors, S. agalactiae infections, normal temperature, thrombocytopenia, leukopenia and mortality, while fever and S. pneumoniae infections were common in CA-LOS. Current initial antibiotic regimens seem adequate, considering the susceptibility patterns of the isolated pathogens. PMID- 27387450 TI - Early evidence of expanding W ST-11 CC meningococcal incidence in Spain. PMID- 27387451 TI - Acute respiratory distress syndrome after aspiration of lamp oil in a fire-eater: a case report. AB - BACKGROUND: Fire-eater's pneumonia is an exogenous chemical pneumonitis after accidental aspiration of hydrocarbon fluids during the act of fire-eating. There have been few case reports in the literature regarding complications after fire eating but so far none, to the best of our knowledge, have described such drastic and life-threatening pulmonary complications as in this case while only having swallowed a small amount of fluid. CASE PRESENTATION: We present a case of fire eater's pneumonia in a 28-year-old white man with severe pulmonary complications. He presented with pneumonitis and partial respiratory insufficiency. He was diagnosed with acute respiratory distress syndrome and was treated with antibiosis, oxygen therapy, and required non-invasive ventilation. He had a good recovery. CONCLUSIONS: Accidental aspiration of even small amounts of lamp oil can lead to serious life-threatening pulmonary complications. Although fire eaters are a comparatively small occupational group, the severity of possible complications illustrates that awareness of these consequences should be raised in teenagers and young adults who might be tempted into trying it. This case in a Western country shows that the dangers of fire-eating are not to be underestimated and are not limited to Eastern European countries where the majority of cases have been reported. PMID- 27387452 TI - A new oridonin analog suppresses triple-negative breast cancer cells and tumor growth via the induction of death receptor 5. AB - Triple-negative breast cancer (TNBC) remains the leading cause of death among women with breast cancer worldwide. Oridonin is a natural anti-cancer compound that is isolated from the traditional Chinese herb Rabdosia rubescens. However, the antitumor efficacies of oridonin in the treatments of TNBC and other cancers are far from ideal. In this study, we investigated a series of newly designed oridonin analogs in terms of their actions against HCC1806 and HCC1937 TNBC cell lines and identified CYD-6-28, which significantly inhibits cancer cell proliferation and induces G2/M-phase cell cycle arrest and apoptosis. CYD-6-28 induces the expression of p21 and the cleavage of caspase-3, -7, -8 and PARP and inhibits the expression levels of Cyclin D1, FLIPL and XIAP. CYD-6-28 also inhibits the activations of STAT3 and AKT and induces the activation of ERK. We demonstrated that CYD-6-28 induces apoptosis at least partially by inducing the expression of death receptor 5 (DR5). Finally, CYD-6-28 significantly suppresses HCC1806 xenograft tumor growth in nude mice at 5 mg/kg without affecting body weight. Taken together, these results indicate that CYD-6-28 has the potential to be developed as a therapeutic agent to treat TNBC. PMID- 27387454 TI - Impact of blood transfusion on gene expression in human reticulocytes. PMID- 27387453 TI - The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice. AB - BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans. PMID- 27387455 TI - Management of Inflammatory Bowel Disease in the Elderly. AB - OPINION STATEMENT: A substantial and growing proportion of patients with inflammatory bowel disease (IBD) are elderly, and these patients require tailored treatment strategies. However, significant challenges exist in the management of this population due to the paucity of data. Establishing the initial diagnosis and assessing the etiology of future symptoms and flares can be challenging as several other prevalent diseases can masquerade as IBD, such as ischemic colitis, diverticular disease, and infectious colitis. Important pharmacologic considerations include reduced glomerular filtration rate and drug-drug interactions in the elderly. No drug therapy is absolutely contraindicated in this population; however, special risk and benefit assessments should be made. Older patients are more susceptible to side effects of steroids such as delirium, fractures, and cataracts. Budesonide can be an appropriate alternative for mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) as it has limited systemic absorption. Pill size and quantity, nephrotoxicity, and difficulty of administration of rectal preparations should be considered with 5-aminosalicylic (5-ASA) therapy. Biologics are very effective, but modestly increase the risk of infection in a susceptible group. Based on their mechanisms, integrin receptor antagonists (e.g., vedolizumab) may reduce these risks. Use of antibiotics for anorectal or fistulizing CD or pouchitis in UC increases the risk of Clostridium difficile infection. Pre-existing comorbidities, functional status, and nutrition are important indicators of surgical outcomes. Morbidity and mortality are increased among IBD patients undergoing surgery, often due to postoperative complications or sepsis. Elderly adults with IBD, particularly UC, have very high rates of venous thromboembolism (VTE). Colonoscopy appears safe, but the optimal surveillance interval has not been well defined. Should the octogenarian, nonagenarian, and centurion undergo colonoscopy? The length of surveillance should likely account for the individual's overall life expectancy. Specific health maintenance should emphasize administering non-live vaccines to patients on thiopurines or biologics and regular skin exams for those on thiopurines. Smoking cessation is crucial to overall health and response to medical therapy, even among UC patients. This article will review management of IBD in the elderly. PMID- 27387456 TI - Minimal important differences for fatigue patient reported outcome measures-a systematic review. AB - BACKGROUND: Fatigue is the most frequent symptom reported by patients with chronic illnesses. As a subjective experience, fatigue is commonly assessed with patient-reported outcome measures (PROMs). Currently, there are more than 40 generic and disease-specific PROMs for assessing fatigue in use today. The interpretation of changes in PROM scores may be enhanced by estimates of the so called minimal important difference (MID). MIDs are not fixed attributes of PROMs but rather vary in relation to estimation method, clinical and demographic characteristics of the study group, etc. The purpose of this paper is to compile published MIDs for fatigue PROMs, spanning diagnostic/patient groups and estimation methods, and to provide information relevant for appraising their appropriateness for use in specific clinical trials and in monitoring fatigue in defined patient groups in routine clinical practice. METHODS: A systematic search of three databases (Scopus, CINAHL and Cochrane) for studies published between January 2000 to April 2015 using fatigue and variations of the term MID, e.g. MCID, MIC, etc. Two authors screened search hits and extracted data independently. Data regarding MIDs, anchors used and study designs were compiled in tables. RESULTS: Included studies (n = 41) reported 60 studies or substudies estimating MID for 28 fatigue scales, subscales or single item measures in a variety of diagnostic groups and study designs. All studies used anchor-based methods, 21/60 measures also included distribution-based methods and 17/60 used triangulation of methods. Both similarities and dissimilarities were seen within the MIDs. CONCLUSIONS: Magnitudes of published MIDs for fatigue PROMs vary considerably. Information about the derivation of fatigue MIDs is needed to evaluate their applicability and suitability for use in clinical practice and research. PMID- 27387457 TI - The Influence of Education on Public Trust and Consent Preferences With Residual Newborn Screening Dried Blood spots. AB - The objectives of this study were to evaluate the impact of educational interventions during prenatal care on public trust for newborn screening and consent preferences for the retention and use of leftover newborn screening dried blood spots. Women who were 30 to 36 weeks pregnant were recruited, and outcomes were measured by telephone survey 2 to 4 weeks postpartum (n = 901). Approximately 40% of the sample chose the opt-out approach but those who watched educational interventions delivered during prenatal care were significantly associated with higher levels of trust and support for an opt-out consent approach. Providing education during prenatal care about newborn screening and the storage and use of leftover dried blood spots along with brochure-based education provided in the hospital when the baby is born is associated with improved trust for the program and support for research with the leftover blood spots. PMID- 27387458 TI - Chemopreventive effect and lack of genotoxicity and mutagenicity of the exopolysaccharide botryosphaeran on human lymphocytes. AB - Carbohydrate biopolymers of fungal-origin are an important natural resource in the search for new bioagents with therapeutic and nutraceutical potential. In this study the mutagenic, genotoxic, antigenotoxic and antioxidant properties of the fungal exopolysaccharide botryosphaeran, a (1->3)(1->6)-beta-D-glucan, from Botryosphaeria rhodina MAMB-05, was evaluated. The mutagenicity was assessed at five concentrations in Salmonella typhimurium by the Ames test. Normal and tumor (Jurkat cells) human T lymphocyte cultures were used to evaluate the genotoxicity and antigenotoxicity (Comet assay) of botryosphaeran alone and in combination with the mutagen methyl methanesulfonate (MMS). The ability of botryosphaeran to reduce the production of reactive oxygen and nitrogen species (RONS) generated by hydrogen peroxide was assessed using the CM-H2DCFDA probe in lymphocyte cultures under different treatment times. None of the evaluated botryosphaeran concentrations were mutagenic in bacteria, nor induced genotoxicity in normal and tumor lymphocytes. Botryosphaeran protected lymphocyte DNA against damage caused by MMS under simultaneous treatment and post-treatment conditions. However, botryosphaeran was not able to reduce the RONS generated by H2O2. Besides the absence of genotoxicity, botryosphaeran exerted a protective effect on human lymphocytes against genotoxic damage caused by MMS. These results are important in the validation of botryosphaeran as a therapeutic agent targeting health promotion. PMID- 27387459 TI - Ultrafast Nanocrystals Decorated Micromotors for On-Site Dynamic Chemical Processes. AB - CdS-polyaniline-Pt and ZnS-polyaniline-Pt micromotors have been synthesized and characterized. The nanocrystals are generated "in situ" during the template electrosynthesis of the micromotors while being simultaneously trapped in the polymeric network, generating a hybrid structure. The presence of nanocrystal "edges" in the inner polyaniline layer result in a rough Pt catalytic surface and enhanced electron transfer for highly efficient bubble propulsion at remarkable speeds of over 2500 MUm/s. The incorporation of CdS and ZnS nanocrystals impart several attractive functions, including cation-exchange based chemical transformation capabilities and enhanced photocatalytic performance. The remarkable ion-exchange properties of ZnS-polyaniline (PANI)-Pt micromotors are illustrated for the cation exchange of heavy metals cations. The superior photocatalytic performance of CdS-PANI-Pt micromotors is used for the enhanced photocatalytic oxidation of bisphenol A. Such self-propelled micromotors act as highly efficient dynamic platforms that offer significantly shorter and more efficient processes as compared with common static operations. The attractive properties of these micromotors will pave the way for diverse sensing, decontamination, energy generation, or electronic applications. PMID- 27387460 TI - Prognostic and predictive significance of tumor length in patients with esophageal squamous cell carcinoma undergoing radical resection. AB - BACKGROUND: The objective of this study was to investigate the prognostic and predictive significance of tumor length in patients with esophageal squamous cell carcinoma undergoing radical resection. METHODS: Tumor length and other clinicopathological variables were retrospectively evaluated in 1435 patients with squamous cell carcinoma treated with radical resection between 2003 and 2010. Tumor length was analyzed as categorical and continuous variable. Associations with overall survival were assessed with Cox proportional hazards models. Model-based nomograms were constructed. Predictive accuracy was measured with C-index. Decision curve analysis was used to evaluate clinical usefulness of prediction models. RESULTS: Both categorically and continuously coded tumor length were independent prognostic factors in multivariable analysis. Adding categorically and continuously coded tumor length to TNM staging model increased predictive accuracy by 0.2 and 0.4 % respectively. Decision curve analysis revealed that the models built by the addition of categorically or continuously coded tumor length did not perform better than TNM staging model. CONCLUSIONS: Tumor length is an independent prognostic factor in patients with esophageal squamous cell carcinoma treated with radical resection. It increases predictive accuracy of TNM staging system for overall survival in these patients. But it does not increase clinical usefulness of TNM staging system as a prediction model. PMID- 27387461 TI - Auto-thiophosphorylation activity of Src tyrosine kinase. AB - BACKGROUND: Intermolecular autophosphorylation at Tyr416 is a conserved mechanism of activation among the members of the Src family of nonreceptor tyrosine kinases. Like several other tyrosine kinases, Src can catalyze the thiophosphorylation of peptide and protein substrates using ATPgammaS as a thiophosphodonor, although the efficiency of the reaction is low. RESULTS: Here, we have characterized the ability of Src to auto-thiophosphorylate. Auto thiophosphorylation of Src at Tyr416 in the activation loop proceeds efficiently in the presence of Ni(2+), resulting in kinase activation. Other tyrosine kinases (Ack1, Hck, and IGF1 receptor) also auto-thiophosphorylate in the presence of Ni(2+). Tyr416-thiophosphorylated Src is resistant to dephosphorylation by PTP1B phosphatase. CONCLUSIONS: Src and other tyrosine kinases catalyze auto thiophosphorylation in the presence of Ni(2+). Thiophosphorylation of Src occurs at Tyr416 in the activation loop, and results in enhanced kinase activity. Tyr416 thiophosphorylated Src could serve as a stable, persistently-activated mimic of Src. PMID- 27387462 TI - Spinal meningioma: relationship between degree of cord compression and outcome. AB - BACKGROUND: The aim of this study was to find the relationships between the degree of cord compression as seen on MRIs with persisting cord atrophy after decompression and patient outcomes in spinal meningiomas. METHOD: We undertook a retrospective analysis of 31 patients' pre- and postoperative MRIs, preoperative functional status and their outcomes at follow-up. The following metrics were analysed; percentage cord area at maximum compression, percentage tumour occupancy and percentage cord occupancy. These were then compared with outcome as measured by the Nurick scale. RESULTS: Of the 31 patients, 27 (87%) had thoracic meningiomas, 3 (10%) cervical and 1 (3%) cervicothoracic. The meningiomas were pathologically classified as grade 1 (29) or grade 2 (2) according to the WHO classification. The average remaining cord cross-sectional area was 61% of the estimated original value. The average tumour occupancy of the canal was 72%. The average cord occupancy of the spinal canal at maximum compression was 20%. No correlation between cord cross-section area and Nurick Scale was seen. On the postoperative scan, the average cord area had increased to 84%. No correlation was seen between this value and outcome. CONCLUSION: We found that cross-section area measurements on MRI scans have no obvious relationship with function before or after surgery. This is a base for future research into the mechanism of cord recovery and other compressive cord conditions. PMID- 27387463 TI - Anxiety and depression, personality traits relevant to tinnitus: A scoping review. AB - OBJECTIVE: Scoping reviews of existing literature were conducted to identify key personality traits relevant to tinnitus, and examine the relationship between affective disorders and tinnitus. DESIGN: The methodological framework of Arksey and O'Malley was followed. STUDY SAMPLE: Sixty studies were chosen for charting the data, 14 studies examined personality traits exclusively, 31 studies examined affective disorders exclusively, and 15 studies investigated both. RESULTS: The presence of one or more specific personality traits of high neuroticism, low extraversion, high stress reaction, higher alienation, lower social closeness, lower well-being, lower self control, lower psychological acceptance, presence of a type D personality, and externalized locus of control were associated with tinnitus distress. Anxiety and depression were more prevalent among the tinnitus clinical population and at elevated levels. CONCLUSIONS: Personality traits have a consistent association with the distress experienced by adult tinnitus help seekers, and help-seekers are also more likely to experience affective symptoms and/or disorders. PMID- 27387464 TI - Safety and Outcomes in Rereduction Mammaplasty: Single Institution Experience and Review of the Literature. AB - BACKGROUND: Reduction mammaplasty is commonly performed for symptomatic macromastia and is useful in achieving symmetry in unilateral breast reconstruction and oncoplastic surgery. Postoperatively, however, recurrent macromastia or asymmetry often develops. In the past, there has been concern about safely resecting additional volume and moving the nipple. We analyze our outcomes with regard to rereduction mammaplasty, (and discuss) these results in comparison to the current literature. METHODS: A retrospective review of patients undergoing rereduction mammaplasty at Emory Hospital from 2008 to 2014 was performed. Prior breast reduction and subsequent removal of additional tissue was required for inclusion. Patient demographics, pedicle selection, time from initial to rereduction, reduction weight, indications, and complications were recorded. RESULTS: Our review identified 37 patients who underwent rereduction mammaplasty. Thirty-four underwent unilateral and 3 underwent bilateral reduction. Average initial reduction weight was 483 g, and average rereduction weight was 226 g. Thirty reductions required nipple areolar complex repositioning; 25 used a superior pedicle, and 5 used a central mound. Eighty three percent of the superior pedicle and 20% of the central mound reductions used the same pedicle. There were 5 complications reported; no cases of nipple necrosis were reported. CONCLUSIONS: With careful technique, rereduction mammaplasty is safe, reliable, and effective. Varying amounts of tissue may be excised, and the nipple may be moved safely with a short superior or central mound pedicle regardless of initial technique. Limited rereduction can be performed as early as 4 to 6 months. PMID- 27387465 TI - Predictors of Complications After Pectoralis Major Transposition for Sternum Dehiscence. AB - OBJECTIVES: Mediastinitis and sternum dehiscence are serious complications after open heart surgery, causing an increase in hospital stay, utilization of health care resources, and mortality. The defect that results after sternal wound debridement frequently necessitates tissue-flap coverage, for which pectoralis major transposition currently is the preferred method. In this study, the postoperative outcome and individual characteristics of patients undergoing pectoralis major transposition were analyzed to identify predictors of complications after wound closure. METHODS: A retrospective chart review was conducted, covering a 7-year period, focusing on patient and operation characteristics. All patients with sternum dehiscence, who underwent pectoralis major transposition, were included. All postoperative wound complications were graded according to the Clavien-Dindo classification of surgical complications. Complications were further divided in major and minor. Mortality was defined as death within 30 days after sternal wound repair or during hospital stay. RESULTS: In total, 77 patients underwent a pectoralis major transposition repair of the sternum. Thirty-eight patients (49%) developed a wound complication of which 21 (27%) had a major wound complication. Mortality was 9%. Further analyses of our data showed that smoking and length of operation time were predictors of wound complications (P = 0.018 and P = 0.01). Female sex showed a relation with wound redehiscence (P = 0.014). Postoperative bleeding, for which reoperation was necessary, occurred more often when the humeral insertion of the pectoralis major flap was divided (P = 0.004). CONCLUSIONS: Tissue-flap coverage of the sternum using pectoralis major advancement flaps is a procedure that is still hampered by a high postoperative complication incidence. Female sex, smoking, detachment of the humeral insertion and operation time are associated with postoperative wound complications. These results may contribute in improving operative strategy. Also the use of the Clavien-Dindo classification makes underestimation of the complication rate unlikely in this study. The classification can easily be used in future studies, which will enhance comparability of results. PMID- 27387466 TI - Total Breast Reconstruction With Fat Grafting After Internal Expansion and Expander Removal. AB - INTRODUCTION: The development of fat grafting techniques both in cosmetic and reconstructive breast surgery has highlighted the need to recreate a breast mound using similar tissues and without visible scarring. Our technique combines skin expansion by conventional expanders and breast volume replacement by serial fat grafting and final expander removal. MATERIALS AND METHODS: Fat grafting had been performed both by Coleman technique and Bodyjet system. We report a series of 12 cases enrolled between 2008 and 2013. Each case has been presented in this article, focusing on received treatment, observed complications, and results. RESULTS: Satisfactory results were observed 6 months after the last session in most of the concluded reconstructions with a low complication rate. PMID- 27387468 TI - Evaporative Water Loss in Superficial to Full Thickness Burns. AB - INTRODUCTION: Increased evaporative water loss (EWL) in burn patients leads to dehydration and hypothermia. Early clinical studies performed with outdated hygrometers suggested a 17 to 75 times increased EWL in burns with contradicting results for the different burn depths.Our study proposals were: (1) obtain reliable data of the EWL of all burn depths, (2) compare these results with findings from earlier studies, (3) evaluate the usefulness of the EWL in differentiating between superficial and deep partial thickness burns, (4) determine the effect of Biobrane on the EWL of superficial partial thickness burns in vivo, and (5) evaluate the effect of the sterile incision foil Opraflex on the EWL in split skin graft donor sites. METHODS: We measured the EWL of all burn depths in 28 patients under stable and recorded conditions regarding room temperature and humidity with a modern digital evaporimeter (Tewameter TM 300). For the first time in vivo, we also determined the effect of Biobrane on the EWL of burns and evaluated the EWL in split skin graft donor sites covered with Opraflex. RESULTS: The EWL in all burn depths was significantly increased (P < 0.001) compared with unburned skin. There was no significant difference (P > 0.05) in the EWL of superficial compared with deep partial thickness burns, whereas full thickness burns had a significantly lower EWL (P < 0.05) compared with superficial and deep partial thickness burns. Biobrane significantly reduced the EWL (P < 0.05) of superficial partial thickness burns. The EWL of Opraflex covered skin graft donor sites was significantly reduced compared with uncovered donor sites (P < 0.05). CONCLUSIONS: Our data suggest that the actual EWL in burns is approximately 3 times higher in full thickness burns and approximately 4 times higher in superficial and deep partial thickness burns compared with normal skin and therefore much lower than suggested previously.Because there was no significant difference in the EWL of superficial compared with deep partial thickness burns, the EWL cannot be used to differentiate between these burn depths.Biosynthetic wound dressings can significantly reduce the EWL of superficial partial thickness burns and sterile incision foil protects split skin graft donor sites from an increased EWL. PMID- 27387469 TI - Color Doppler Ultrasonography-Targeted Perforator Mapping and Angiosome-Based Flap Reconstruction. AB - Knowledge about perforators and angiosomes has inspired new and innovative flap designs for reconstruction of defects throughout the body. The purpose of this article is to share our experience using color Doppler ultrasonography (CDU) targeted perforator mapping and angiosome-based flap reconstruction throughout the body. The CDU was used to identify the largest and best-located perforator adjacent to the defect to target the reconstruction. The cutaneous or fasciocutaneous flaps were raised, mobilized, and designed according to the reconstructive needs as rotation, advancement, or turnover flaps. We performed 148 reconstructions in 130 patients. Eleven facial reconstructions, 118 reconstructions in the body, 7 in the upper limbs, and 12 in the lower limbs. The propeller flap was used in 135 of 148 (91%) cases followed by the turnover design in 10 (7%) and the V to Y flap in 3 (2%) cases. The flaps were raised on 1 perforator in 98 (67%), 2 perforators in 48 (33%), and 3 perforators in 2 (1%) flaps. The reconstructive goal was achieved in 143 of 148 reconstructions (97%). In 5 cases, surgical revision was needed. No flaps were totally lost indicating a patent pedicle in all cases. We had 10 (7%) cases of major complications and 22 (15%) minor complications. The CDU-targeted perforator mapping and angiosome based flap reconstruction are simple to perform, and we recommended its use for freestyle perforator flap reconstruction. All perforators selected by CDU was identified during surgery and used for reconstruction. The safe boundaries of angiosomes remain to be established. PMID- 27387470 TI - Simple Reshaping of the Breast in Massive Weight Loss Patients: Promising Preliminary Results. AB - BACKGROUND: The challenging breast reshaping after massive weight loss (MWL) has been increasingly performed as the number of bariatric surgery procedures increase worldwide. The breasts often appear wide, lateralized, and deflated, with significant ptosis. OBJECTIVES: The aim of this article is to share our initial experience using the lower pole subglandular advancement mastoplasty (LOPOSAM) technique to reshape the breasts in MWL patients and to elaborate the technical details and simplicity of the method in the attached video. MATERIALS AND METHODS: We performed 30 LOPOSAM procedures in 15 MWL women aged 24 to 63 years from February to September 2015. We used a wise pattern mark-up and a superior based pedicle for the relocation of the nipple areola complex. The key step for the autoaugmentation was an inferior and central mound based parabola shaped flap, which was placed in a subglandular pocket to reshape the breast and lift the inframammary crease. RESULTS: The median operation time for the LOPOSAM procedure was 81 minutes (range, 35-160 minutes) by 2 surgeons. The median weight loss was 64 kg (range, 45-103) and 22 body mass index units (range, 16-33) per patient. The median follow-up was 240 days (range, 105 Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation to 345). The surgical goal was achieved in all cases. Four complications occurred in 3 patients, 1 major, a hematoma-requiring surgery and 3 minor wound dehiscence. The self-reported patient satisfaction was high, 13 were very satisfied with the result, 1 satisfied, and 1 less satisfied. CONCLUSIONS: The LOPOSAM technique is quick and simple to perform, and the preliminary results are promising. However, a longer follow-up is needed to confirm this. PMID- 27387471 TI - Closing the net on retroviruses. AB - Structural studies reveal how an antiviral factor forms a molecular net to restrict retroviruses including HIV-1. PMID- 27387472 TI - Low-dose rituximab is poorly effective in patients with primary membranous nephropathy. AB - Background: The optimal dosing and the efficacy of rituximab for primary membranous nephropathy (PMN) has not been established. This multicentric prospective study evaluates the efficacy and safety of low-dose rituximab (RTX) therapy in patients with PMN in clinical practice. Methods: Thirty-four consecutive patients with PMN and nephrotic syndrome were included and received RTX (375 mg/m2) once (18 patients) or twice (16 patients). RTX was the first-line therapy for 19 (56%) and the second line for 15 (44%) patients. All patients were followed for 12 months after RTX and 24 for at least 18 months (mean 23.9 +/- 18.6 months). Results: At 12 months, 5 patients (14.7%) achieved complete response, 10 (29.4%) partial and 19 (55.8%) no response. Response occurred ~6 months after RTX. At 24 months, the clinical situation was unchanged: two non responders achieved partial response and two responders relapsed. Responders had significantly higher baseline GFR and lower anti-PLA2R antibodies compared with non-responders. Outcome was similar between one or two doses of RTX (non responders 55.5 versus 56%, respectively) and between patients who had received previous therapy versus those receiving RTX as first-line therapy (non-responders 40 versus 68%, respectively). In the 15 patients already treated, the response to RTX was comparable to that of previous therapies. Conclusion: Low-dose RTX obtains remission in <50% of PMN patients. Probably, higher doses and longer treatments are needed to induce and maintain a response. The balance between the costs and benefits should guide the selection of the patient and the optimal dosage. PMID- 27387473 TI - A urinary proteome-based classifier for the early detection of decline in glomerular filtration. AB - Background: Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be late-stage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m 2 . Methods: A total of 2672 patients with different CKD stages were included in the study. Of these, 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m 2 /year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of >=80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m 2 . In addition, areas under the curve for CKD273 and UAE were calculated. Results: In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. Conclusions: These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE. PMID- 27387474 TI - Emerging role of Lipopolysaccharide binding protein in sepsis-induced acute kidney injury. AB - Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review. PMID- 27387475 TI - The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients. AB - BACKGROUND: We sought to determine whether the mode of sensitization in highly sensitized patients contributed to kidney allograft survival. METHODS: An analysis of the United Network for Organ Sharing dataset involving all kidney transplants between 1997 and 2014 was undertaken. Highly sensitized adult kidney transplant recipients [panel reactive antibody (PRA) >=98%] were compared with adult, primary non-sensitized and re-transplant recipients. Kaplan-Meier survival analyses were used to determine allograft survival rates. Cox proportional hazards regression analyses were conducted to determine the association of graft loss with key predictors. RESULTS: Fifty-three percent of highly sensitized patients transplanted were re-transplants. Pregnancy and transfusion were the only sensitizing event in 20 and 5%, respectively. The 10-year actuarial graft survival for highly sensitized recipients was 43.9% compared with 52.4% for non sensitized patients, P < 0.001. The combination of being highly sensitized by either pregnancy or blood transfusion increased the risk of graft loss by 23% [hazard ratio (HR) 1.230, confidence interval (CI) 1.150-1.315, P < 0.001], and the combination of being highly sensitized from a prior transplant increased the risk of graft loss by 58.1% (HR 1.581, CI 1.473-1.698, P < 0.001). CONCLUSIONS: The mode of sensitization predicts graft survival in highly sensitized kidney transplant recipients (PRA >=98%). Patients who are highly sensitized from re transplants have inferior graft survival compared with patients who are highly sensitized from other modes of sensitization. PMID- 27387476 TI - Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome. AB - Background: Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder, secondary to mutations in the GATA-3 gene. Due to its wide range of penetrance and expressivity, the disease may not always be recognized. We herein describe clinical and genetic features of patients with HDR syndrome, highlighting diagnostic clues. Methods: Medical records of eight patients from five unrelated families exhibiting GATA-3 mutations were reviewed retrospectively, in conjunction with all previously reported cases. Results: HDR syndrome was diagnosed in eight patients between the ages of 18 and 60 years. Sensorineural deafness was consistently diagnosed, ranging from clinical hearing loss since infancy in seven patients to deafness detected only by audiometry in adulthood in one single patient. Hypoparathyroidism was present in six patients (with hypocalcaemia and inaugural seizures in two out of six). Renal abnormalities observed in six patients were diverse and of dysplastic nature. Three patients displayed nephrotic-range proteinuria and reached end-stage renal disease (ESRD) between the ages of 19 and 61 years, whilst lesions of focal and segmental glomerulosclerosis were histologically demonstrated in one of them. Interestingly, phenotype severity differed significantly between a mother and son within one family. Five new mutations of GATA-3 were identified, including three missense mutations affecting zinc finger motifs [NM_001002295.1: c.856A>G (p.N286D) and c.1017C>G (p.C339W)] or the conserved linker region [c.896G>A (p.R299G)], and two splicing mutations (c.924+4_924+19del and c.1051-2A>G). Review of 115 previously reported cases of GATA-3 mutations showed hypoparathyroidism and deafness in 95% of patients, and renal abnormalities in only 60%. Overall, 10% of patients had reached ESRD. Conclusions: We herein expand the clinical and mutational spectrum of HDR syndrome, illustrating considerable inter- and intrafamilial phenotypic variability. Diagnosis of HDR should be considered in any patient with hypoparathyroidism and deafness, whether associated with renal abnormalities or not. HDR diagnosis is established through identification of a mutation in the GATA-3 gene. PMID- 27387477 TI - Supramolecular Affinity Labeling of Histone Peptides Containing Trimethyllysine and Its Application to Histone Deacetylase Assays. AB - Lysine methylation is an important histone post-translational modification (PTM) for manipulating chromatin structure and regulating gene expression, and its dysregulation is associated with various diseases including many cancers. While characterization of Lys methylation has seen improvements over the past decade due to advances in proteomic mass spectrometry and methods involving antibodies, chemical methods for selective detection of proteins containing PTMs are still lacking. Here, we detail the development of a unique labeling method wherein a synthetic receptor probe for trimethyl lysine (Kme3), CX4-ONBD, is used to direct selective fluorescent labeling of Kme3 histone peptides. This supramolecular approach reverses the paradigm of ligand-directed affinity labeling by making the receptor the synthetic component and the ligand the component to be labeled. We show that the probe mediates a strong turn-on fluorescence response in the presence of a Kme3 histone peptide and shows >5-fold selectivity in covalent labeling over an unmethylated lysine peptide. We also demonstrate the utility of the probe through the design of a turn-on fluorescence assay for histone deacetylase (HDAC) activity and for inhibitor screening and IC50 determination. Our synthetic receptor-mediated affinity labeling approach broadens the scope of PTM detection by chemical means and may facilitate the development of more versatile in vitro enzymatic assays. PMID- 27387478 TI - Changes in Activated Thrombin-Activatable Fibrinolysis Inhibitor Levels Following Thrombolytic Therapy in Ischemic Stroke Patients Correlate with Clinical Outcome. AB - BACKGROUND AND PURPOSE: Thrombin-activatable fibrinolysis inhibitor (TAFI) activation following thrombolysis may affect thrombolysis effectiveness in acute ischemic stroke (AIS). To support this hypothesis, we propose to study the relationship between TAFI consumption, activated/inactivated TAFI (TAFIa/ai) and stroke severity and outcome in 2 groups of AIS patients, one treated and one untreated with intravenous recombinant tissue type plasminogen activator (rt-PA). METHODS: In this prospective, longitudinal, multicenter, observational study, we aimed to study the association between TAFIa/ai and stroke outcome. TAFI levels were sequentially measured in patients treated with intravenous rt-PA thrombolysis (T), and in patients not given any thrombolytic therapy (NT). Baseline reference values were established in healthy subjects matched for age and gender. The National Institutes of Health Stroke Scale (NIHSS) score assessed at baseline and on day 2 was dichotomized into 2 severity groups (0-7 vs. >7). The modified Rankin Scale (mRS) score at day 90 was dichotomized for favorable (0 1) and unfavorable (2-6) outcomes. RESULTS: A total of 109 patients were included, with 41 receiving rt-PA. At admission, patients had higher TAFIa/ai levels than reference. A significant increase in TAFIa/ai levels was observed at the end of thrombolysis (mean change from baseline of 963%) and lasted up to 4 h (191%). Higher TAFIa/ai levels were associated with a more severe day 2 NIHSS score (p = 0.0098 at T2h post thrombolysis) and an unfavorable mRS score from T48h (p = 0.0417) to day 90 (p = 0.0046). In NT patients, higher TAFIa/ai levels at admission were associated with a more severe stroke, as assessed by day 2 NIHSS score (p = 0.0026) and mRS score (p = 0.0003). CONCLUSION: These data demonstrate a consistent relationship between TAFI levels and early clinical severity during rt-PA treatment. PMID- 27387479 TI - Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Screening and Decolonization to Reduce Surgical Site Infection in Elective Total Joint Arthroplasty. AB - BACKGROUND: Deep infection after elective total joint arthroplasty remains a devastating complication. Preoperative nasal swab screening for Staphylococcus aureus colonization and subsequent treatment of colonized patients is one proposed method to identify at-risk patients and decrease surgical site infections (SSIs). The purpose of this study was to determine whether a preoperative staphylococcus screening and treatment program would decrease the incidence of SSI in elective joint arthroplasty patients. METHODS: Since January 2009, a total of 9690 patients having an elective joint arthroplasty were screened before surgery for Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) with nares swabs. All patients with positive nare colonization for MSSA and MRSA were treated with mupirocin and chlorhexidine gluconate showers for 5 days before surgery. MRSA patients received vancomycin preoperatively and were placed in contact isolation. All elective arthroplasty patients used chlorhexidine gluconate antiseptic cloths the evening prior and the day of surgery. Perioperative infection rates were compared from 1 year before implementation to 5 years after implementation of this screening protocol. RESULTS: SSI rates have decreased from 1.11% (prescreening) to 0.34% (nasal screening; P < .05) after initiation of the process. Staphylococcus was identified in 66.7% of the SSI infections before nasal screening and in 33.3% of the SSI after routine screening (P > .05). CONCLUSION: The addition of MRSA and/or MSSA nares screening along with a perioperative decolonization protocol has resulted in a decreased SSI rate by 69%. PMID- 27387480 TI - Preoperative Risk Factors Associated With Poor Outcomes of Revision Surgery for "Pseudotumors" in Patients With Metal-on-Metal Hip Arthroplasty. AB - BACKGROUND: Revision surgery of failed metal-on-metal (MoM) total hip arthroplasty (THA) for adverse tissue reaction (pseudotumor) can be challenging as a consequence of soft tissue and muscle necrosis. The aims of this study were to (1) report the revision outcomes of patients who underwent revision surgery for failed MoM hip arthroplasty due to symptomatic pseudotumor and (2) identify preoperative risk factors associated with revision outcomes. METHODS: Between January 2011 and January 2013, a total of 102 consecutive large head MoM hip arthroplasties in 97 patients (male: 62, female: 35), who underwent revision surgery were identified from the database of a multidisciplinary referral center. RESULTS: At minimum follow-up of 2 years (range: 26-52 months), at least one complication had occurred in 14 of 102 revisions (14%). Prerevision radiographic loosening (P = .01), magnetic resonance imaging (MRI) findings of solid lesions with abductor deficiency on MRI (P < .001), and intraoperative grading of adverse tissue reactions (P = .05) were correlated with post-revision complications. The reoperation rate of revised MoM THA was 7% (7 of 102 hips). Implant survivorship was 88% at 3 years. Metal ion levels declined in most patients after removal of MoM articulation. CONCLUSION: Revision outcomes of revision surgery for failed MoM THA due to symptomatic pseudotumor demonstrated 14% complication rate and 7% re-revision rate at 30-month follow-up. Our study identified prerevision radiographic loosening, solid lesions/abductor deficiency on MRI, and high grade intraoperative tissue damage as risk factors associated with poorer revision outcomes. This provides clinically useful information for preoperative planning and perioperative counseling of MoM THA patients undergoing revision surgery. PMID- 27387481 TI - Liganded Thyroid Hormone Receptors Transactivate the DNA Methyltransferase 3a Gene in Mouse Neuronal Cells. AB - Thyroid hormone (T3) is essential for proper neurological development. The hormone, bound to its receptors, regulates gene transcription in part by modulating posttranslational modifications of histones. Methylation of DNA, which is established by the de novo DNA methyltransferase (DNMT)3a and DNMT3b, and maintained by DNMT1 is another epigenetic modification influencing gene transcription. The expression of Dnmt3a, but not other Dnmt genes, increases in mouse brain in parallel with the postnatal rise in plasma [T3]. We found that treatment of the mouse neuroblastoma cell line Neuro2a[TRbeta1] with T3 caused rapid induction of Dnmt3a mRNA, which was resistant to protein synthesis inhibition, supporting that it is a direct T3-response gene. Injection of T3 into postnatal day 6 mice increased Dnmt3a mRNA in the brain by 1 hour. Analysis of two chromatin immunoprecipitation-sequencing datasets, and targeted analyses using chromatin immunoprecipitation, transfection-reporter assays, and in vitro DNA binding identified 2 functional T3-response elements (TREs) at the mouse Dnmt3a locus located +30.3 and +49.3 kb from the transcription start site. Thyroid hormone receptors associated with both of these regions in mouse brain chromatin, but with only 1 (+30.3 kb) in Neuro2a[TRbeta1] cells. Deletion of the +30.3-kb TRE using CRISPR/Cas9 genome editing eliminated or strongly reduced the Dnmt3a mRNA response to T3. Bioinformatics analysis showed that both TREs are highly conserved among eutherian mammals. Thyroid regulation of Dnmt3a may be an evolutionarily conserved mechanism for modulating global changes in DNA methylation during postnatal neurological development. PMID- 27387483 TI - Application of Personalized, Predictive, Preventative, and Participatory (P4) Medicine to Obstructive Sleep Apnea. A Roadmap for Improving Care? AB - Dr. Leroy Hood promotes a paradigm to advance medical care that he calls P4 medicine. The four Ps are: personalized, predictive, preventative, and participatory. P4 medicine encourages a convergence of systems medicine, the digital revolution, and consumer-driven healthcare. Might P4 medicine be applicable to obstructive sleep apnea (OSA)? OSA should be personalized in that there are different structural and physiological pathways to disease. Obesity is a major risk factor. The link between obesity and OSA is likely to be fat deposits in the tongue compromising the upper airway. Clinical features at presentation also vary between patients. There are three distinct subgroups: (1) patients with a primary complaint of insomnia, (2) relatively asymptomatic patients with a high prevalence of cardiovascular comorbidities, and (3) excessively sleepy patients. Currently, there have been limited efforts to identify subgroups of patients on the basis of measures obtained by polysomnography. Yet, these diagnostic studies likely contain considerable predictive information. Likewise, there has currently been limited application of -omic approaches. Determining the relative role of obesity and OSA for particular consequences is challenging, because they both affect the same molecular pathways. There is evidence that the effects of OSA are modified by the level of obesity. These insights may lead to improvements in predicting outcomes to personalized therapies. The final P-participatory-is ideally suited to OSA, with technology to obtain extensive data remotely from continuous positive airway pressure machines. Providing adherence data directly to patients increases their use of continuous positive airway pressure. Thus, the concept of P4 medicine is very applicable to obstructive sleep apnea and can be the basis for future research efforts. PMID- 27387484 TI - Charge Inversion and Topological Phase Transition at a Twist Angle Induced van Hove Singularity of Bilayer Graphene. AB - van Hove singularities (VHS's) in the density of states play an outstanding and diverse role for the electronic and thermodynamic properties of crystalline solids. At the critical point the Fermi surface connectivity changes, and topological properties undergo a transition. Opportunities to systematically pass a VHS at the turn of a voltage knob and study its diverse impact are however rare. With the advent of van der Waals heterostructures, control over the atomic registry of neighboring graphene layers offers an unprecedented tool to generate a low energy VHS easily accessible with conventional gating. Here we have addressed magnetotransport when the chemical potential crosses the twist angle induced VHS in twisted bilayer graphene. A topological phase transition is experimentally disclosed in the abrupt conversion of electrons to holes or vice versa, a loss of a nonzero Berry phase and distinct sequences of integer quantum Hall states above and below the singularity. PMID- 27387482 TI - Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice. AB - CRH neurons in the hypothalamic paraventricular nucleus (PVN) play a central role in regulating the hypothalamus-pituitary-adrenal (HPA) axis and are directly influenced by 17beta-estradiol (E2). Although compelling evidence has suggested the existence of membrane-associated estrogen receptors (mERs) in hypothalamic and other central nervous system neurons, it remains unknown whether E2 impacts CRH neuronal excitability through this mechanism. The purpose of the current study is to examine the existence and function of mER signaling in PVN CRH neurons. Whole-cell recordings were made from CRH neurons identified by Alexa Fluor 594 labeling and post hoc immunostaining in ovariectomized female mice. E2 (100nM) rapidly suppressed the M-current (a voltage-dependent K(+) current) and potentiated glutamatergic excitatory postsynaptic currents. The putative Gq coupled mER (Gq-mER) characterized in hypothalamic proopiomelanocortin neurons initiates a phospholipase C-protein kinase C-protein kinase A pathway; therefore, we examined the involvement of this pathway using selective inhibitors. Indeed, the ER antagonist ICI 182780 and inhibitors of Gq-phospholipase C-protein kinase C-protein kinase A blocked E2's actions, suggesting dependence on the Gq-mER. Furthermore, STX, a selective ligand for the Gq-mER, mimicked E2's actions. Finally, to examine the in vivo effect of Gq-mER activation, E2 or STX injection increased c-fos expression in CRH neurons in the PVN, suggesting CRH neuronal activation. This corresponded to an increase in plasma corticosterone. We conclude that the Gq-mER plays a critical role in the rapid regulation of CRH neuronal activity and the HPA axis. Our findings provide a potential underlying mechanism for E2's involvement in the pathophysiology of HPA-associated mood disorders. PMID- 27387485 TI - Single-Locus versus Multilocus Patterns of Local Adaptation to Climate in Eastern White Pine (Pinus strobus, Pinaceae). AB - Natural plant populations are often adapted to their local climate and environmental conditions, and populations of forest trees offer some of the best examples of this pattern. However, little empirical work has focused on the relative contribution of single-locus versus multilocus effects to the genetic architecture of local adaptation in plants/forest trees. Here, we employ eastern white pine (Pinus strobus) to test the hypothesis that it is the inter-genic effects that primarily drive climate-induced local adaptation. The genetic structure of 29 range-wide natural populations of eastern white pine was determined in relation to local climatic factors using both a reference set of SSR markers, and SNPs located in candidate genes putatively involved in adaptive response to climate. Comparisons were made between marker sets using standard single-locus outlier analysis, single-locus and multilocus environment association analyses and a novel implementation of Population Graphs. Magnitudes of population structure were similar between the two marker sets. Outlier loci consistent with diversifying selection were rare for both SNPs and SSRs. However, genetic distances based on the multilocus among population covariances (cGD) were significantly more correlated to climate, even after correcting for spatial effects, for SNPs as compared to SSRs. Coalescent simulations confirmed that the differences in mutation rates between SSRs and SNPs did not affect the topologies of the Population Graphs, and hence values of cGD and their correlations with associated climate variables. We conclude that the multilocus covariances among populations primarily reflect adaptation to local climate and environment in eastern white pine. This result highlights the complexity of the genetic architecture of adaptive traits, as well as the need to consider multilocus effects in studies of local adaptation. PMID- 27387487 TI - Experimentalisierung und internationale Kommunikationen: Der Fall Curare. PMID- 27387486 TI - Enzymes involved in the anaerobic degradation of ortho-phthalate by the nitrate reducing bacterium Azoarcus sp. strain PA01. AB - The pathway of anaerobic degradation of o-phthalate was studied in the nitrate reducing bacterium Azoarcus sp. strain PA01. Differential two-dimensional protein gel profiling allowed the identification of specifically induced proteins in o phthalate-grown compared to benzoate-grown cells. The genes encoding o-phthalate induced proteins were found in a 9.9 kb gene cluster in the genome of Azoarcus sp. strain PA01. The o-phthalate-induced gene cluster codes for proteins homologous to a dicarboxylic acid transporter, putative CoA-transferases and a UbiD-like decarboxylase that were assigned to be specifically involved in the initial steps of anaerobic o-phthalate degradation. We propose that o-phthalate is first activated to o-phthalyl-CoA by a putative succinyl-CoA-dependent succinyl-CoA:o-phthalate CoA-transferase, and o-phthalyl-CoA is subsequently decarboxylated to benzoyl-CoA by a putative o-phthalyl-CoA decarboxylase. Results from in vitro enzyme assays with cell-free extracts of o-phthalate-grown cells demonstrated the formation of o-phthalyl-CoA from o-phthalate and succinyl-CoA as CoA donor, and its subsequent decarboxylation to benzoyl-CoA. The putative succinyl-CoA:o-phthalate CoA-transferase showed high substrate specificity for o phthalate and did not accept isophthalate, terephthalate or 3-fluoro-o-phthalate whereas the putative o-phthalyl-CoA decarboxylase converted fluoro-o-phthalyl-CoA to fluoro-benzoyl-CoA. No decarboxylase activity was observed with isophthalyl CoA or terephthalyl-CoA. Both enzyme activities were oxygen-insensitive and inducible only after growth with o-phthalate. Further degradation of benzoyl-CoA proceeds analogous to the well-established anaerobic benzoyl-CoA degradation pathway of nitrate-reducing bacteria. PMID- 27387488 TI - Epidemiological, Clinical and Virological Characteristics of Influenza B Virus from Patients at the Hospital Tertiary Care Units in Bangkok during 2011-2014. AB - Influenza B virus, which causes acute respiratory infections, has increased in prevalence in recent years. Based on the nucleotide sequence of the hemagglutinin (HA) gene, influenza B virus can be divided into two lineages, Victoria and Yamagata, that co-circulate during the influenza season. However, analysis of the potential association between the clinical and virological characteristic and the lineage of influenza B viruses isolated in Thailand was lacking. To investigate influenza B virus genetically and determine its neuraminidase (NA) inhibitor susceptibility phenotype, a total of 6920 nasopharyngeal-wash samples were collected from patients with influenza-like illness between the years 2011 and 2014 and were screened for influenza B virus by real-time PCR. Of these samples, 3.1% (216/6920) were confirmed to contain influenza B viruses, and 110 of these influenza viruses were randomly selected for nucleotide sequence analysis of the HA and NA genes. Phylogenetic analysis of the HA sequences showed clustering into various clades: Yamagata clade 3 (11/110, 10%), Yamagata clade 2 (71/110, 64.5%), and Victoria clade 1 (28/110, 25.5%). The analysis of clinical characteristic demonstrated that the Victoria lineage was significantly associated with the duration of hospitalization, number of deceased cases, pneumonia, secondary bacterial infection and underlying disease. When combined with phylogenetic analysis of the NA sequences, four samples showed viruses with reassortant sequences between the Victoria and Yamagata lineages. Statistical analysis of the clinical outcomes and demographic data for the reassortant strains did not differ from those of the other strains in circulation. Oseltamivir-resistant influenza B viruses were not detected. Our findings indicated the co-circulation of the Victoria and Yamagata lineages over the past four cold seasons in Bangkok. We also demonstrated differences in the clinical symptoms between these lineages. PMID- 27387490 TI - Self-assembly of a space-tessellating structure in the binary system of hard tetrahedra and octahedra. AB - We report the formation of a binary crystal of hard polyhedra due solely to entropic forces. Although the alternating arrangement of octahedra and tetrahedra is a known space-tessellation, it had not previously been observed in self assembly simulations. Both known one-component phases - the dodecagonal quasicrystal of tetrahedra and the densest-packing of octahedra in the Minkowski lattice - are found to coexist with the binary phase. Apart from an alternative, monoclinic packing of octahedra, no additional crystalline phases were observed. PMID- 27387489 TI - Impact of Non-Invasively Induced Motor Deficits on Tibial Cortical Properties in Mutant Lurcher Mice. AB - It has been shown that Lurcher mutant mice have significantly altered motor abilities, regarding their motor coordination and muscular strength because of olivorecebellar degeneration. We assessed the response of the cross-sectional geometry and lacuno-canalicular network properties of the tibial mid-diaphyseal cortical bone to motor differences between Lurcher and wild-type (WT) male mice from the B6CBA strain. The first data set used in the cross-sectional geometry analysis consists of 16 mice of 4 months of age and 32 mice of 9 months of age. The second data set used in the lacunar-canalicular network analysis consists of 10 mice of 4 months of age. We compared two cross-sectional geometry and four lacunar-canalicular properties by I-region using the maximum and minimum second moment of area and anatomical orientation as well as H-regions using histological differences within a cross section. We identified inconsistent differences in the studied cross-sectional geometry properties between Lurcher and WT mice. The biggest significant difference between Lurcher and WT mice is found in the number of canaliculi, whereas in the other studied properties are only limited. Lurcher mice exhibit an increased number of canaliculi (p < 0.01) in all studied regions compared with the WT controls. The number of canaliculi is also negatively correlated with the distance from the centroid in the Lurcher and positively correlated in the WT mice. When the Lurcher and WT sample is pooled, the number of canaliculi and lacunar volume is increased in the posterior Imax region, and in addition, midcortical H-region exhibit lower number of canaliculi, lacuna to lacuna distance and increased lacunar volume. Our results indicate, that the importance of precise sample selection within cross sections in future studies is highlighted because of the histological heterogeneity of lacunar-canalicular network properties within the I-region and H-region in the mouse cortical bone. PMID- 27387491 TI - A case report of primary cardiac myxofibrosarcoma presenting with severe congestive heart failure. AB - BACKGROUND: Primary cardiac sarcomas are extremely rare. Furthermore, the myxofibrosarcomas are one of the rarest forms of cardiac sarcomas, and its prognosis is known to be quite poor. CASE PRESENTATION: This is a case of a 23 year-old man who presented with acute severe congestive heart failure caused by almost complete obstruction of the mitral valve due to a large left atrial tumor. The patient required endotracheal intubation before his arrival to the hospital, and underwent an emergent surgical excision of the tumor. The tumor had a complex shape and originated from the orifice of the right upper pulmonary vein. Because the tumor seemed to extend over most of the surface of the left atrium, it seemed impossible to reconstruct the left atrium had we done a complete transmural resection. Instead, we carefully peeled the tumor leaving the outer layer of the left atrial wall. We applied cryoablation to the attached site, in order to prevent a recurrence of the tumor. The pathology report revealed that the tumor was a myxofibrosarcoma, and it seemed to originate from the heart. The patient received radiation therapy after the surgery and continues to be alive and well after 1-year, without apparent recurrence. CONCLUSIONS: Cardiac myxofibrosarcoma can cause acute, severe left-sided heart failure. Non-transmural atrial wall resection with cryoablation might be effective for patients with cardiac myxofibrosarcomas with extensive atrial attachment. PMID- 27387492 TI - Erratum: Transcript and Metabolite Profiling for the Evaluation of Tobacco Tree and Poplar as Feedstock for the Bio-based Industry. AB - A correction was made to: Transcript and Metabolite Profiling for the Evaluation of Tobacco Tree and Poplar as Feedstock for the Bio-based Industry. There was a spelling error in one of the authors' surname. The author's name was corrected from: Juan Pedro Navarro to: Juan Navarro-Avino. PMID- 27387493 TI - Acute effect of stretching modalities and time-pressure on accuracy and consistency of throwing darts among 12- and 13-year-old schoolboys. AB - BACKGROUND: The present study addressed the lack of data on the effect of different types of stretching on selected measures of throwing accuracy. We hypothesized that the stretching procedures, within pre-exercise warm-up, could affect the accuracy and the consistency in throwing darts performances under different stress conditions. METHODS: Eighteen right-handed schoolboys (13.1+/ 0.4 years, 166+/-0.1 cm and 54.5+/-9 kg; mean+/-SD) completed the Darts Throwing Accuracy Test in free (FDT) and in time-pressure (TPDT) conditions, either after static (SS), dynamic (DS), ballistic (BS) or no-stretching (NS) protocols, on nonconsecutive days and in a counter-balanced randomized order. After performing 5 minutes of light standardized jogging and one of the three stretching protocols for 10 minutes, each participant completed the FDT and TPDT tests. Mean scores, missed darts and variability of scores, were recorded and analyzed using a two way ANOVA with repeated measures. Heart rate (HR), ratings of perceived exertion (RPE) and the task difficulty perception (DP), were recorded through each experimental session. RESULTS: There was no effect of the stretching procedures on accuracy in FDT. However, in the TPDT condition, better performances were recorded after NS and SS compared to DS and BS. The accuracy performances decreased in TPDT by 9.6% after NS (P<0.01); 15.3% after DS (P<0.001) and 11.8% after BS (P<0.001); but not after SS (P<0.05). CONCLUSIONS: Static stretching helped reducing the adverse effects of time-pressure on darts throwing performance. Consequently, static exercises are recommended before practicing activities requiring both upper limbs speed and accuracy. PMID- 27387494 TI - Efficacy of kinesio taping versus postural correction exercises on pain intensity and axioscapular muscles activation in mechanical neck dysfunction: a randomized blinded clinical trial. AB - BACKGROUND: While postural correction is commonly used for mechanical neck dysfunction (MND), efficacy of KT has received considerable attention. This study was conducted to determine the effectiveness of kinesio taping (KT) versus postural correction exercises on pain intensity and axioscapular muscles activation in patients with MND. METHODS: Randomized clinical trial for which forty six patients with MND were randomly assigned in to 1 of 2 groups received 4 weeks treatment; KT group: received kinesio taping, PCE group: performed postural correction exercises. Neck pain and axioscapular muscles activation in form of normalized root mean square of dominant upper trapezius and levator scapula muscles were measured pre- and post-treatment by visual analogue scale and electromyography. Two ways MANOVA was used to examine the effects of treatment on outcome measures. The variable of interest was the group-by-time interaction at an a priori alpha level of 0.05. Intragroup comparisons were performed using paired t-tests. RESULTS: Group by time interaction was statistically significant in multivariate test (F=3.114, P=0.031). KT produced more pain reduction than postural exercises (P<0.05). There was no significant interaction for either UT RMS (P=0.274) or LS RMS (P=0.59). In both groups, Paired t tests revealed that there was significant reduction in pain and muscle activation of both measured muscles (P<0.01). CONCLUSIONS: KT has been found to be more effective than postural exercises to reduce neck pain. However, both modalities have similar effects to reduce axioscapular muscles activation. PMID- 27387495 TI - Prevalence rate of chronic overuse pain in taekwondo athletes. AB - BACKGROUND: The aim of this study was to estimate the prevalence of chronic overuse pain (COP) and to identify possible risk factors of COP in sport poomsae taekwondo. METHODS: This is a cross-sectional survey. A total of 263 sport poomsae competitors (112 females; 151 males; aged between 12-44 years), who competed at the 2014 sport poomsae taekwondo competition, participated in this study. The prevalence rate of COP and possible risk factors associated with COP were analyzed by using Chi-square tests and independent t-tests. RESULTS: A total of 173 athletes reported that they experienced COP (65.8%; 95% confidence interval [CI]: 60.5-71.5). Female athletes showed a higher prevalence rate than their male counterparts (75.9% vs. 58.3%). Lower body (61.5%) and knee joints (26.4%) were the two primarily injured body part. A total of 101 athletes reported that they injured in the previous year. Among those, 81.2% were suffered from COP. The technique that caused pain most frequently was side-kick among females and front-kick among males. Prevalence rates of COP were significantly different by sex, education level, training hour, and a history of injury. CONCLUSIONS: The prevalence of COP is high among sport poomsae taekwondo athletes. Competitors who are female, have a history of injury, and train for extended hours were more likely to experience COP. To identify other potential risk factors of COP in sport poomsae taekwondo, more research is needed to build upon the findings. PMID- 27387496 TI - Reproducibility of the intermittent Spartacus Run Test in obese adolescents. AB - BACKGROUND: Evaluating physical fitness in obese children is a core element of their clinical management that requires population specific and reliable standards to detect estimates of functional capacity. The aims of the present study were: 1) to estimate the reproducibility of the newly developed Spartacus intermittent run test in adolescents with obesity; and 2) to compare the Spartacus Test with two commonly used tests (20-meter shuttle run test [20-SRT] and the multistage track test) for assessing functional capacity in this population. METHODS: Twelve obese adolescent girls (12-15-years old, BMI: 34.5+/ 4.1 kg/m2) performed a 20-SRT, a multistage track test (MSTT) and the Spartacus Test. The Spartacus Test was performed three times to evaluate its reproducibility. Maximal speed, maximal heart rate (HRmax) and rate of perceived exertion (RPE) were measured following each test. RESULTS: The adolescents reached higher maximal speeds following the Spartacus test compared to the two other tests (P<0.001 for both). HRmax was significantly higher following the Spartacus test (194.3+/-12.4 bpm) compared to 20-SRT (173.5+/-4.7 bpm) and MSTT (182.4+/-11.0 bpm) (P<0.001 for both). However, RPE was not significantly different between tests. Furthermore, the Intra-Class Coefficient between the three Spartacus tests was 0.922 [0.777 - 0.979] for the maximal speed with a variation coefficient of only 5%. CONCLUSIONS: The Spartacus intermittent test is a reproducible test to assess functional capacity in adolescents with obesity. It could then be integrated into the childhood obesity interventions. PMID- 27387497 TI - Effects of combined high intensity arm and leg training on performance and cardio respiratory measures. AB - BACKGROUND: The purpose of this study was to investigate the effects of combined arm and leg high-intensity low-volume interval training (HIITarm+leg) on maximal oxygen uptake, myocardial measures (i.e. stroke volume, cardiac output, ejection fraction), Tissue Oxygenation Index (TOI) of the vastus lateralis and triceps brachii, as well as power output in comparison to leg HIIT (HIITleg) only. METHODS: The 20 healthy, male and female volunteers completed six sessions of either HIITleg on a cycle ergometer or HIITarm+leg on an arm and leg cycle ergometer. During pre- and post-testing, the volunteers completed a submaximal and incremental test to exhaustion on a cycle ergometer. RESULTS: Magnitude based interference revealed likely to very likely beneficial effects for HIITarm+leg compared to HIITleg in maximal oxygen uptake, cardiac measures as well peak power output. The TOI following HIITarm+leg demonstrated likely to very likely increased oxygenation in the triceps brachii or the vastus lateralis when compared to HIITleg. CONCLUSIONS: The results suggest that six sessions of HIITarm+leg may likely to very likely improve maximal oxygen uptake, some inotropy-related cardiac measures with improved tissue oxygenation of the triceps brachii and vastus lateralis muscles resulting in greater leg peak power output. PMID- 27387498 TI - Diagnosis and management of benign fibro-osseous lesions of the jaws: a current review for the dental clinician. AB - Benign fibro-osseous lesions of the maxillofacial skeleton constitute a heterogeneous group of disorders that includes developmental, reactive (dysplastic) and neoplastic lesions. Although their classification has been reviewed multiple times in the past, the most common benign fibro-osseous lesions are fibrous dysplasia, osseous dysplasia and ossifying fibroma. For the dental clinician, the challenges involve diagnosis and treatment (or lack thereof). A careful correlation of all clinical, radiologic and microscopic features is essential to establish a proper diagnosis and a clear treatment plan. This article aimed to review the clinical, radiologic and histopathologic characteristics of benign fibro-osseous lesions of the jaws, with emphasis on their differential diagnoses. With a deeper understanding of benign fibro-osseous lesions, clinicians will be better prepared to manage these lesions in their practice. PMID- 27387499 TI - Protein Arginine Methyltransferase Product Specificity Is Mediated by Distinct Active-site Architectures. AB - In the family of protein arginine methyltransferases (PRMTs) that predominantly generate either asymmetric or symmetric dimethylarginine (SDMA), PRMT7 is unique in producing solely monomethylarginine (MMA) products. The type of methylation on histones and other proteins dictates changes in gene expression, and numerous studies have linked altered profiles of methyl marks with disease phenotypes. Given the importance of specific inhibitor development, it is crucial to understand the mechanisms by which PRMT product specificity is conferred. We have focused our attention on active-site residues of PRMT7 from the protozoan Trypanosoma brucei We have designed 26 single and double mutations in the active site, including residues in the Glu-Xaa8-Glu (double E) loop and the Met-Gln-Trp sequence of the canonical Thr-His-Trp (THW) loop known to interact with the methyl-accepting substrate arginine. Analysis of the reaction products by high resolution cation exchange chromatography combined with the knowledge of PRMT crystal structures suggests a model where the size of two distinct subregions in the active site determines PRMT7 product specificity. A dual mutation of Glu-181 to Asp in the double E loop and Gln-329 to Ala in the canonical THW loop enables the enzyme to produce SDMA. Consistent with our model, the mutation of Cys-431 to His in the THW loop of human PRMT9 shifts its product specificity from SDMA toward MMA. Together with previous results, these findings provide a structural basis and a general model for product specificity in PRMTs, which will be useful for the rational design of specific PRMT inhibitors. PMID- 27387500 TI - Molecular Basis Behind Inability of Mitochondrial Holocytochrome c Synthase to Mature Bacterial Cytochromes: DEFINING A CRITICAL ROLE FOR CYTOCHROME c alpha HELIX-1. AB - Mitochondrial holocytochrome c synthase (HCCS) is required for cytochrome c (cyt c) maturation and therefore respiration. HCCS efficiently attaches heme via two thioethers to CXXCH of mitochondrial but not bacterial cyt c even though they are functionally conserved. This inability is due to residues in the bacterial cyt c N terminus, but the molecular basis is unknown. Human cyts c with deletions of single residues in alpha helix-1, which mimic bacterial cyt c, are poorly matured by human HCCS. Focusing on DeltaM13 cyt c, we co-purified this variant with HCCS, demonstrating that HCCS recognizes the bacterial-like cytochrome. Although an HCCS-WT cyt c complex contains two covalent links, HCCS-DeltaM13 cyt c contains only one thioether attachment. Using multiple approaches, we show that the single attachment is to the second thiol of C(15)SQC(18)H, indicating that alpha helix-1 is required for positioning the first cysteine for covalent attachment, whereas the histidine of CXXCH positions the second cysteine. Modeling of the N-terminal structure suggested that the serine residue (of CSQCH) would be anchored where the first cysteine should be in DeltaM13 cyt c An engineered cyt c with a CQCH motif in the DeltaM13 background is matured at higher levels (2-3-fold), providing further evidence for alpha helix-1 positioning the first cysteine. Bacterial cyt c biogenesis pathways (Systems I and II) appear to recognize simply the CXXCH motif, not requiring alpha helix-1. Results here explain mechanistically how HCCS (System III) requires an extended region adjacent to CXXCH for maturation. PMID- 27387501 TI - Citrobacter rodentium NleB Protein Inhibits Tumor Necrosis Factor (TNF) Receptor associated Factor 3 (TRAF3) Ubiquitination to Reduce Host Type I Interferon Production. AB - Interferon signaling plays important roles in both intestinal homeostasis and in the host response to pathogen infection. The extent to which bacterial pathogens inhibit this host pathway is an understudied area of investigation. We characterized Citrobacter rodentium strains bearing deletions in individual type III secretion system effector genes to determine whether this pathogen inhibits the host type I IFN response and which effector is responsible. The NleB effector limited host IFN-beta production by inhibiting Lys(63)-linked ubiquitination of TNF receptor-associated factor 3 (TRAF3). Inhibition was dependent on the glycosyltransferase activity of NleB. GAPDH, a target of NleB during infection, bound to TRAF3 and was required for maximal TRAF3 ubiquitination. NleB glycosyltransferase activity inhibited GAPDH-TRAF3 binding, resulting in reduced TRAF3 ubiquitination. Collectively, our data reveal important interplay between GAPDH and TRAF3 and suggest a mechanism by which the NleB effector inhibits type I IFN signaling. PMID- 27387502 TI - Kelch-like Protein 21 (KLHL21) Targets IkappaB Kinase-beta to Regulate Nuclear Factor kappa-Light Chain Enhancer of Activated B Cells (NF-kappaB) Signaling Negatively. AB - Activation of IKKbeta is the key step in canonical activation of NF-kappaB signaling. Extensive work has provided insight into the mechanisms underlying IKKbeta activation through the identification of context-specific regulators. However, the molecular processes responsible for its negative regulation are not completely understood. Here, we identified KLHL21, a member of the Kelch-like gene family, as a novel negative regulator of IKKbeta. The expression of KLHL21 was rapidly down-regulated in macrophages upon treatment with proinflammatory stimuli. Overexpression of KLHL21 inhibited the activation of IKKbeta and degradation of IkappaBalpha, whereas KLHL21 depletion via siRNA showed the opposite results. Coimmunoprecipitation assays revealed that KLHL21 specifically bound to the kinase domain of IKKbeta via its Kelch domains and that this interaction was gradually attenuated upon TNFalpha treatment. Furthermore, KLHL21 did not disrupt the interaction between IKKbeta and TAK1, TRAF2, or IkappaBalpha. Also, KLHL21 did not require its E3 ubiquitin ligase activity for IKKbeta inhibition. Our findings suggest that KLHL21 may exert its inhibitory function by binding to the kinase domain and sequestering the region from potential IKKbeta inducers. Taken together, our data clearly demonstrate that KLHL21 negatively regulates TNFalpha-activated NF-kappaB signaling via targeting IKKbeta, providing new insight into the mechanisms underlying NF-kappaB regulation in cells. PMID- 27387504 TI - NDST2 (N-Deacetylase/N-Sulfotransferase-2) Enzyme Regulates Heparan Sulfate Chain Length. AB - Analysis of heparan sulfate synthesized by HEK 293 cells overexpressing murine NDST1 and/or NDST2 demonstrated that the amount of heparan sulfate was increased in NDST2- but not in NDST1-overexpressing cells. Altered transcript expression of genes encoding other biosynthetic enzymes or proteoglycan core proteins could not account for the observed changes. However, the role of NDST2 in regulating the amount of heparan sulfate synthesized was confirmed by analyzing heparan sulfate content in tissues isolated from Ndst2(-/-) mice, which contained reduced levels of the polysaccharide. Detailed disaccharide composition analysis showed no major structural difference between heparan sulfate from control and Ndst2(-/-) tissues, with the exception of heparan sulfate from spleen where the relative amount of trisulfated disaccharides was lowered in the absence of NDST2. In vivo transcript expression levels of the heparan sulfate-polymerizing enzymes Ext1 and Ext2 were also largely unaffected by NDST2 levels, pointing to a mode of regulation other than increased gene transcription. Size estimation of heparan sulfate polysaccharide chains indicated that increased chain lengths in NDST2 overexpressing cells alone could explain the increased heparan sulfate content. A model is discussed where NDST2-specific substrate modification stimulates elongation resulting in increased heparan sulfate chain length. PMID- 27387503 TI - Molecular Interactions of Human Plasminogen with Fibronectin-binding Protein B (FnBPB), a Fibrinogen/Fibronectin-binding Protein from Staphylococcus aureus. AB - Staphylococcus aureus is a commensal bacterium that has the ability to cause superficial and deep-seated infections. Like several other invasive pathogens, S. aureus can capture plasminogen from the human host where it can be converted to plasmin by host plasminogen activators or by endogenously expressed staphylokinase. This study demonstrates that sortase-anchored cell wall associated proteins are responsible for capturing the bulk of bound plasminogen. Two cell wall-associated proteins, the fibrinogen- and fibronectin-binding proteins A and B, were found to bind plasminogen, and one of them, FnBPB, was studied in detail. Plasminogen captured on the surface of S. aureus- or Lactococcus lactis-expressing FnBPB could be activated to the potent serine protease plasmin by staphylokinase and tissue plasminogen activator. Plasminogen bound to recombinant FnBPB with a KD of 0.532 MUm as determined by surface plasmon resonance. Plasminogen binding did not to occur by the same mechanism through which FnBPB binds to fibrinogen. Indeed, FnBPB could bind both ligands simultaneously indicating that their binding sites do not overlap. The N3 subdomain of FnBPB contains the full plasminogen-binding site, and this includes, at least in part, two conserved patches of surface-located lysine residues that were recognized by kringle 4 of the host protein. PMID- 27387507 TI - What Brexit means for the European Working Time Directive. PMID- 27387505 TI - Lunapark Is a Component of a Ubiquitin Ligase Complex Localized to the Endoplasmic Reticulum Three-way Junctions. AB - The endoplasmic reticulum (ER) network comprises sheets and tubules that are connected by dynamic three-way junctions. Lunapark (Lnp) localizes to and stabilizes ER three-way junctions by antagonizing the small GTPase Atlastin, but how Lnp shapes the ER network is unclear. Here, we used an affinity purification approach and mass spectrometry to identify Lnp as an interacting partner of the ER protein quality control ubiquitin ligase gp78. Accordingly, Lnp purified from mammalian cells has a ubiquitin ligase activity in vitro Intriguingly, biochemical analyses show that this activity can be attributed not only to associated ubiquitin ligase, but also to an intrinsic ubiquitin ligase activity borne by Lnp itself. This activity is contained in the N-terminal 45 amino acids of Lnp although this segment does not share homology to any known ubiquitin ligase motifs. Despite its interaction with gp78, Lnp does not seem to have a broad function in degradation of misfolded ER proteins. On the other hand, the N terminal ubiquitin ligase-bearing motif is required for the ER three-way junction localization of Lnp. Our study identifies a new type of ubiquitin ligase and reveals a potential link between ubiquitin and ER morphology regulation. PMID- 27387506 TI - Artificial sweeteners and metabolic dysregulation: Lessons learned from agriculture and the laboratory. AB - Escalating rates of obesity and public health messages to reduce excessive sugar intake have fuelled the consumption of artificial sweeteners in a wide range of products from breakfast cereals to snack foods and beverages. Artificial sweeteners impart a sweet taste without the associated energy and have been widely recommended by medical professionals since they are considered safe. However, associations observed in long-term prospective studies raise the concern that regular consumption of artificial sweeteners might actually contribute to development of metabolic derangements that lead to obesity, type 2 diabetes and cardiovascular disease. Obtaining mechanistic data on artificial sweetener use in humans in relation to metabolic dysfunction is difficult due to the long time frames over which dietary factors might exert their effects on health and the large number of confounding variables that need to be considered. Thus, mechanistic data from animal models can be highly useful because they permit greater experimental control. Results from animal studies in both the agricultural sector and the laboratory indicate that artificial sweeteners may not only promote food intake and weight gain but can also induce metabolic alterations in a wide range of animal species. As a result, simple substitution of artificial sweeteners for sugars in humans may not produce the intended consequences. Instead consumption of artificial sweeteners might contribute to increases in risks for obesity or its attendant negative health outcomes. As a result, it is critical that the impacts of artificial sweeteners on health and disease continue to be more thoroughly evaluated in humans. PMID- 27387508 TI - High-throughput detection and quantification of mitochondrial fusion through imaging flow cytometry. AB - Mitochondria are highly dynamic organelles whose fusion and fission play an increasingly important role in a number of both normal and pathological cellular functions. Despite the increased interest in mitochondrial dynamics, robust, and quantitative methods to analyze mitochondrial fusion and fission activity in intact cells have not been developed. The current state-of-the art method to measure mitochondrial fusion activity is the polyethylene glycol (PEG) fusion assay in which cells expressing distinct mitochondrially-targeted fluorescent proteins (FPs) are fused together and mitochondrial fusion activity is determined by the rate at which color mixing occurs. Although this assay is useful, cell cell fusion events are rare, and finding the number of fused cells required to generate statistically rigorous data is both tedious and time-consuming. Furthermore, the data-collection methods available for fluorescence microscopy lead to inherent selection biases that are difficult to control for. To that end, we have developed an unbiased and high-throughput method to detect, image, and analyze fused cells using the Amnis ImagestreamXTM MKII. With IDEASTM software, we developed algorithms for identifying the fused cells (two nuclei within a single cell), distinguishing them from cell aggregates. Additionally, using the fluorescence localization of the mitochondrially-targeted fluorescent proteins (YFP and DsRed), we applied a modified co-localization algorithm to identify those cells that had a high co-localization score indicating mitochondrial fusion activity. These algorithms were tested using negative controls (FPs associated with fusion deficient mitochondria) and positive controls (cells expressing both FPs in the same mitochondria). Once validated these algorithms could be applied to test samples to evaluate the degree of mitochondrial fusion in cells with various genetic mutations. Ultimately, this new method is the first robust, high throughput way to directly measure mitochondrial fusion in intact cells. Given how many cellular processes are being linked mitochondrial dynamics, this technique will provide a powerful new tool in the study of this important organelle. (c) 2016 International Society for Advancement of Cytometry. PMID- 27387510 TI - Intolerance to environmental chemicals and sounds in irritable bowel syndrome: Explained by central sensitization? AB - This study tested the hypotheses of irritable bowel syndrome showing (1) comorbidity with chemical and sound intolerance, other types of functionally somatic syndromes, and psychiatric disorders and (2) stronger than normal affective reactions to and behavioral disruptions from odorous/pungent chemicals and sounds in daily life. These hypotheses were tested by means of data from a large-scale population-based questionnaire study. The results showed comorbidity in irritable bowel syndrome with chemical and sound intolerance, fibromyalgia, migraine, post-traumatic stress disorder, generalized anxiety disorder, panic syndrome, and depression as well as strong reactions/disruptions from odorous/pungent chemicals and sounds in irritable bowel syndrome. PMID- 27387509 TI - [Differential diagnosis of leg edema]. AB - There are not only patients with leg edema provoked by venous disorders who come to consult a phlebologist, but patients with a wide range of leg edemas of different origin. Therefore it demands great skills to take into consideration the different pattern of leg edema. This overview presents the characteristics of leg edema and the most frequently underlying disorders. Tables for differential diagnosis, medical history and physical examination and further investigations are added. PMID- 27387511 TI - Qualitative inquiry into reasons why vaccination messages fail. AB - A growing tendency to refuse child vaccination is commonly regarded as a reason for concern. Attempts to promote vaccination by authorities often prove to be unsuccessful or even counter-productive. The aim of this study was to explore how parents perceived four messages used to promote vaccination. In eight focus groups ( N = 73), we presented participants with messages and asked them to assess them. Using thematic analysis, we identified themes that our participants considered the most important. Messages that promote vaccination should be unambiguous, more balanced, not focus on repeating the negative effects of vaccine-preventable diseases and provide links to the evidence. PMID- 27387512 TI - Gaining qualitative insight into the subjective experiences of adherers to an exercise referral scheme: A thematic analysis. AB - Nine adults who had completed an exercise referral scheme participated in a semi structured interview to uncover the key psychological factors associated with adherence to the scheme. Through thematic analysis, an exercise identity emerged to be a major factor associated with adherence to the scheme, which was formed of a number of underpinning constructs including changes in self-esteem, changes in self-efficacy and changes in self-regulatory strategies. Also, an additional theme of transitions in motivation to exercise was identified, showing participants' motivation to alter from extrinsic to intrinsic reasons to exercise during the scheme. PMID- 27387513 TI - Using a theoretical approach to identify factors influencing adherence to an exercise programme for adults with venous leg ulcers. AB - This study assessed the relationships between self-efficacy, outcome expectations, fear-avoidance beliefs and adherence to an exercise for a home based exercise programme for adults with venous leg ulcers. Patients ( n=63) were randomised to receive either an intervention or usual care group. Of those in the exercise intervention group, 59per cent adhered to the exercise protocol more than 75per cent of the time. There was a significant relationship between self efficacy and outcome expectations, and both of these constructs were significantly related to adherence to the leg exercise programme. Adherence significantly correlated with wound healing indicating a possible pathway to healing. PMID- 27387514 TI - Changing health-promoting behaviours through narrative interventions: A systematic review. AB - The objective of this review was to summarize the literature supporting narrative interventions that target health-promoting behaviours. Eligible articles were English-language peer-reviewed studies that quantitatively reported the results of a narrative intervention targeting health-promoting behaviours or theoretical determinants of behaviour. Five public health and psychology databases were searched. A total of 52 studies met inclusion criteria. In all, 14 studies found positive changes in health-promoting behaviours after exposure to a narrative intervention. The results for the changes in theoretical determinants were mixed. While narrative appears to be a promising intervention strategy, more research is needed to determine how and when to use these interventions. PMID- 27387516 TI - [Not Available]. PMID- 27387515 TI - [Not Available]. PMID- 27387517 TI - HAL2 overexpression induces iron acquisition in bdf1Delta cells and enhances their salt resistance. AB - The yeast Saccharomyces cerevisiae is capable of responding to various environmental stresses, such as salt stress. Such responses require a complex network and adjustment of the gene expression network. The goal of this study is to further understand the molecular mechanism of salt stress response in yeast, especially the molecular mechanism related to genes BDF1 and HAL2. The Bromodomain Factor 1 (Bdf1p) is a transcriptional regulator, which is part of the basal transcription factor TFIID. Cells lacking Bdf1p are salt sensitive with an abnormal mitochondrial function. We previously reported that the overexpression of HAL2 or deletion of HDA1 lowers the salt sensitivity of bdf1Delta. To better understand the mechanism behind the HAL2-related response to salt stress, we compared three global transcriptional profiles (bdf1Delta vs WT, bdf1Delta + HAL2 vs bdf1Delta, and bdf1Deltahda1Delta vs bdf1Delta) in response to salt stress using DNA microarrays. Our results reveal that genes for iron acquisition and cellular and mitochondrial remodeling are induced by HAL2. Overexpression of HAL2 decreases the concentration of nitric oxide. Mitochondrial iron-sulfur cluster (ISC) assembly also decreases in bdf1Delta + HAL2. These changes are similar to the changes of transcriptional profiles induced by iron starvation. Taken together, our data suggest that mitochondrial functions and iron homeostasis play an important role in bdf1Delta-induced salt sensitivity and salt stress response in yeast. PMID- 27387518 TI - Agrobacterium-mediated insertional mutagenesis in the mycorrhizal fungus Laccaria bicolor. AB - Agrobacterium-mediated gene transfer (AMT) is extensively employed as a tool in fungal functional genomics and accordingly, in previous studies we used AMT on a dikaryotic strain of the ectomycorrhizal basidiomycete Laccaria bicolor. The interest in this fungus derives from its capacity to establish a symbiosis with tree roots, thereby playing a major role in nutrient cycling of forest ecosystems. The ectomycorrhizal symbiosis is a highly complex interaction involving many genes from both partners. To advance in the functional characterization of fungal genes, AMT was used on a monokaryotic L. bicolor. A collection of over 1200 transgenic strains was produced, of which 200 randomly selected strains were analyzed for their genomic T-DNA insertion patterns. By means of insertional mutagenesis, a number of transgenic strains were obtained displaying differential growth features. Moreover, mating with a compatible strain resulted in dikaryons that retained altered phenotypic features of the transgenic monokaryon. The analysis of the T-DNA integration pattern revealed mostly similar results to those reported in earlier studies, confirming the usefulness of AMT on different genetic backgrounds of L. bicolor. Taken together, our studies display the great versatility and potentiality of AMT as a tool for the genetic characterization of L. bicolor. PMID- 27387519 TI - The bacterial divisome: more than a ring? AB - Bacterial cells are critically dependent on their ability to divide. The process of division is carried out by a large and highly dynamic molecular machine, known as the divisome. An understanding of the divisomes' architecture is highly sought after, as it is essential for understanding molecular mechanisms and potentially designing antibiotic molecules that curb bacterial growth. Our current view, which is mainly based on high-resolution imaging of Escherichia coli, is that it is a patchy ring or toroid structure. However, recent super-resolution imaging has shown that the toroid structure contains at least three concentric rings, each containing a different set of proteins. Thus, the emerging picture is that the divisome has different functional modules that are spatially separated in concentric rings. PMID- 27387520 TI - Review of the clinical significance of respiratory virus infections in newborn infants. AB - Respiratory viruses have been recognised as causative agents for a wide spectrum of clinical manifestations and severe respiratory compromise in neonates during birth hospitalisation. Early-life respiratory virus infections have also been shown to be associated with adverse long-term consequences. CONCLUSION: Preventing virus infections by intensifying hygiene measures and cohorting infected infants should be a major goal for neonatal intensive care units, as well as more common use of virus diagnostics. Active virus surveillance and long term follow-up are needed to ascertain the causality and exact underlying mechanisms for adverse long-term consequences. PMID- 27387521 TI - Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high-efficiency SPECT. AB - BACKGROUND: Ejection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT. METHODS: Fifty patients (mean age 69 years) undergoing regadenoson same-day rest (8-11 mCi)/stress (32-42 mCi) Tc 99m gated HE SPECT were enrolled. Stress imaging was started 1 minute after sequential intravenous regadenoson .4 mg and Tc-99m injections, and was composed of five 2 minutes supine gated acquisitions followed by two 4 minutes supine and upright images. Ischemic total perfusion deficit (ITPD) >=5 % was considered as significant ischemia. RESULTS: Significantly lower mean EF reserve was obtained in the 5th and 9th minute after regadenoson bolus in patients with significant ischemia vs patients without (5th minute: -4.2 +/- 4.6% vs 1.3 +/- 6.6%, P = .006; 9th minute: -2.7 +/- 4.8% vs 2.0 +/- 6.6%, P = .03). CONCLUSIONS: Negative EF reserve obtained between 5th and 9th minutes of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of transient ischemic functional changes with Tc-99m HE-SPECT. PMID- 27387522 TI - Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity, cardiac function, exercise capacity, and symptom in patients with chronic heart failure and Cheyne-Stokes respiration. AB - PURPOSE: Adaptive servo-ventilation (ASV) therapy has been reported to be effective for improving central sleep apnea (CSA) and chronic heart failure (CHF). The purpose of this study was to clarify whether ASV is effective for CSA, cardiac sympathetic nerve activity (CSNA), cardiac symptoms/function, and exercise capacity in CHF patients with CSA and Cheyne-Stokes respiration (CSR CSA). METHODS: In this study, 31 CHF patients with CSR-CSA and a left ventricular ejection fraction (LVEF) <= 40% were randomized into an ASV group and a conservative therapy (non-ASV) group for 6 month. Nuclear imagings with 123I Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. CSNA was evaluated by 123I-MIBG imaging, with the delayed heart/mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). RESULTS: The ASV group had significantly better (P < .05) results than the non-ASV group with respect to the changes of AHI (-20.8 +/- 14.6 vs -0.5 +/- 8.1), TDS (-7.9 +/- 4.3 vs 1.4 +/- 6.0), and H/M(0.16 +/- 0.16 vs 0.04 +/- 0.10) on 123I-MIBG imaging, as well as the changes of LVEF (5.3 +/- 3.9% vs 0.7 +/- 32.6%), SAS (1.6 +/- 1.4 vs 0.3 +/- 0.7), and NYHA class (2.2 +/- 0.4 vs 2.7 +/- 0.5) after 6-month therapy. CONCLUSIONS: Performing ASV for 6 months achieved improvement of CSR-CSA, CSNA, cardiac symptoms/function, and exercise capacity in CHF patients with CSR-CSA. PMID- 27387523 TI - Superoxide dismutase 2 knockdown leads to defects in locomotor activity, sensitivity to paraquat, and increased cuticle pigmentation in Tribolium castaneum. AB - Insects can rapidly adapt to environmental changes through physiological responses. The red flour beetle Tribolium castaneum is widely used as a model insect species. However, the stress-response system of this species remains unclear. Superoxide dismutase 2 (SOD2) is a crucial antioxidative enzyme that is found in mitochondria. T. castaneum SOD2 (TcSOD2) is composed of 215 amino acids, and has an iron/manganese superoxide dismutase domain. qRT-PCR experiments revealed that TcSOD2 was present through all developmental stages. To evaluate TcSOD2 function in T. castaneum, we performed RNAi and also assessed the phenotype and antioxidative tolerance of the knockdown of TcSOD2 by exposing larvae to paraquat. The administration of paraquat resulted in significantly higher 24-h mortality in TcSOD2 knockdown larval groups than in the control groups. The TcSOD2 knockdown adults moved significantly more slowly, had lower ATP content, and exhibited a different body color from the control groups. We found that TcSOD2 dsRNA treatment in larvae resulted in increased expression of tyrosinase and laccase2 mRNA after 10 days. This is the first report showing that TcSOD2 has an antioxidative function and demonstrates that T. castaneum may use an alternative antioxidative system when the SOD2-based system fails. PMID- 27387524 TI - Interprofessional Screening, Brief Intervention, and Referral to Treatment (SBIRT) Education for Registered Nurses and Behavioral Health Professionals. AB - Although substance use is prevalent in the United States, the majority of people who misuse substances do not receive appropriate treatment. This paper describes, (1) an interprofessional education (IPE) program for health professionals to provide Screening Brief Intervention and Referral to Treatment to rural substance use patients, and (2) compares registered nurses' [RNs] and behavioral health professionals' [BHPs] attitudes to work with those patients and their perceptions on IPE. A data analysis of 62 RNs and 36 BHPs shows statistically significant increases in both attitudes and perceptions. This paper discusses the implications of the IPE program vis-a-vis substance use treatment. PMID- 27387526 TI - Sentence Processing in Traumatic Brain Injury: Evidence From the P600. AB - PURPOSE: Sentence processing can be affected following a traumatic brain injury (TBI) due to linguistic or cognitive deficits. Language-related event-related potentials (ERPs), particularly the P600, have not been described in individuals with TBI history. METHOD: Four young adults with a history of closed head injury participated. Two had severe injuries, and 2 had mild-moderate injuries more than 24 months prior to testing. ERPs were recorded while participants read sentences designed to be grammatically correct or incorrect. Participants also completed cognitive and sentence comprehension measures. RESULTS: One participant with TBI was significantly different than the control group on several behavioral sentence measures and 1 cognitive measure. However, none of the participants with TBI had a reliable P600 effect. Nonparametric bootstrapping indicated that the ERP was reliable in 10 control participants but no participants with TBI history. CONCLUSIONS: There were few behavioral differences between individuals with TBI history and the control group, though all reported subjective difficulty with reading. The P600 was absent in the TBI group in this study. Given the heterogeneity of individuals with TBI and the difficulty in assessing subtle language impairments, exploring the P600 further may provide useful insight into language processing difficulties. PMID- 27387525 TI - A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses. AB - RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses. PMID- 27387527 TI - The effect of plasma from septic ICU patients on healthy rat muscle mitochondria. AB - BACKGROUND: Although sepsis-induced organ failure is a major cause of death in ICU worldwide, the associated mitochondrial dysfunction is not fully characterized and there is presently no evidence of causality. In this study, we examined whether a central factor in septic plasma could directly affect respiratory function of healthy rat muscle mitochondria. METHODS: ICU patients with severe sepsis or septic shock were recruited within 24 h of admission together with age-matched controls. Blood samples were centrifuged and immediately frozen. Two trials were performed, and mitochondrial respiration was analyzed using an Oxygraph chamber with a Clark-electrode. (1) Isolated mitochondria from the rat skeletal muscle were divided and incubated for 30 min with plasma from patients or postoperative controls (n = 10). Respiration was normalized for citrate synthase activity. (2) Permeabilized muscle fibers from rats were divided and incubated with plasma from patients or healthy controls, for 30 and 120 min, and analyzed for mitochondrial respiration (n = 10). Respiration was normalized for wet weight. Primary outcome was state 3 respiration, corresponding to the maximal respiration initiated by ADP and energy substrates (malate and pyruvate). T test was used for statistical comparison. RESULTS: No differences in respiratory function of the mitochondria were seen between the groups in either of the experiments. (1) State 3 respiration of isolated mitochondria were 19.9 +/- 6.7 vs. 20.2 +/- 8.8 nmol O2 * U CS(-1) * min(-1) for sepsis vs. control, respectively. (2) State 3 respiration for fibers incubated with septic and control plasma were after 30 min 2.6 +/- 0.3 vs. 2.4 +/ 0.7 and after 120 min 2.5 +/- 0.4 vs. 2.5 +/- 0.6 nmol O2 * mg * w.w(-1) * min( 1). Respiratory control ratios were good in all experiments (8.8-11.2), ensuring functioning mitochondria. CONCLUSIONS: These findings indicate that muscle mitochondria are not directly influenced by a factor in plasma of septic patients. The effects seen in mitochondrial function in sepsis may rather be a result of intracellular processes and signaling, such as e.g., production of reactive oxygen species. PMID- 27387528 TI - Transcriptional reprogramming of metabolic pathways in critically ill patients. AB - BACKGROUND: Critical illness causes a shift away from mitochondrial metabolism towards a greater dependence on glycolysis. This metabolic shift is thought to be associated with lactic acidosis, organ dysfunction and poor clinical outcomes. The current paradigm is that low oxygen supply causes regional hypoxia, which in turn drives such a metabolic shift. In this study, we evaluated whether the shift towards glycolysis can also occur in cells where oxygen supply is plentiful. METHODS: We used circulating blood cells from non-hypoxic critically ill patients (n = 47) as a model to study cellular metabolism in a normal oxygen milieu. We measured the transcriptomic profiles of canonical metabolic pathways in these cells and compared them to cells obtained from healthy controls (n = 18). RESULTS: Transcriptomic profiling revealed a significant reprogramming of metabolic pathways during critical illness. In well-oxygenated cells, there was a reduced expression of tricarboxylic acid cycle genes and genes associated with pyruvate entry into the mitochondria suggesting decreased mitochondrial oxidation. In contrast, glycolysis was accelerated, as reflected by an up regulation of genes coding for enzymes of early and late glycolytic pathway that were associated with increased lactate production. The pentose phosphate pathway genes for NADPH production were also up-regulated suggesting enhanced antioxidant production during increased oxidative stress. CONCLUSIONS: Contrary to the established paradigm, aerobic glycolysis does occur in non-hypoxic cells during critical illness and its occurrence may represent an adaptive strategy common to cells under increased oxidative stress. Further study of this previously under recognized metabolic phenomenon might identify novel drug target for antioxidant therapy. PMID- 27387529 TI - Changes in the membrane fatty acid composition in Anoxybacillus flavithermus subsp. yunnanensis E13T as response to solvent stress. AB - Anoxybacillus flavithermus subsp. yunnanensis is currently the first species of strictly thermophilic bacteria that is able to tolerate a broad range of solvents. Unlike most of solvent-tolerant mesophilic bacteria, the bacterium does not synthesize unsaturated fatty acids. Our results revealed that in growing cells of A. flavithermus subsp. yunnanensis E13T, ethanol and toluene resulted in an increase in straight-chain fatty acids, mainly C16:0, leading to a more rigid membrane. Moreover, the increase in straight-chain fatty acids caused by ethanol was much higher than that of toluene. High temperature had little effect on the fatty acid composition by itself, whereas the combined conditions of high temperature and ethanol caused the dramatic increase in straight-chain fatty acids (mainly C16:0), that was balanced by decreasing branched fatty acids. The increase was also temperature dependent. The proportion of C16:0 further increased above 60 degrees C. No similar evidence was found in four other species of Anoxybacillus. The results suggested that A. flavithermus subsp. yunnanesis seems to develop a different response to solvents compared to its mesophilic counterparts, which consist of an increase in the saturated straight/branched ratio. PMID- 27387530 TI - Fifth International Symposium on Metallomics 2015. PMID- 27387531 TI - AbetaPP processing results in greater toxicity per amount of Abeta1-42 than individually expressed and secreted Abeta1-42 in Drosophila melanogaster. AB - The aggregation of the amyloid-beta (Abeta) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimer's disease (AD). Abeta peptides are generated from proteolytic processing of the transmembrane Abeta precursor protein (AbetaPP) via sequential proteolysis through the beta-secretase activity of beta-site AbetaPP-cleaving enzyme (BACE1) and by the intramembranous enzyme gamma-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD associated gene products in vivo In one model, the Abeta peptide is directly over expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human AbetaPP is co-expressed with human BACE1, resulting in production of the Abeta peptide through the processing of AbetaPP by BACE1 and by endogenous fly gamma-secretase. Here, we performed a parallel study of flies that expressed the Abeta1-42 peptide alone or that co expressed AbetaPP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the Abeta1-42, Abeta1-40 and Abeta1-38 peptides were examined. Our data reveal that the toxic effect per amount of detected Abeta1-42 peptide was higher in the flies co-expressing AbetaPP and BACE1 than in the Abeta1-42-expressing flies, and that the co-existence of Abeta1 42 and Abeta1-40 in the flies co-expressing AbetaPP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the Abeta1-42 peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research. PMID- 27387532 TI - Ultra-superovulation for the CRISPR-Cas9-mediated production of gene-knockout, single-amino-acid-substituted, and floxed mice. AB - Current advances in producing genetically modified mice using genome-editing technologies have indicated the need for improvement of limiting factors including zygote collection for microinjection and their cryopreservation. Recently, we developed a novel superovulation technique using inhibin antiserum and equine chorionic gonadotropin to promote follicle growth. This method enabled the increased production of fertilized oocytes via in vitro fertilization compared with the conventional superovulation method. Here, we verify that the ultra-superovulation technique can be used for the efficient generation of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9)-mediated knockout mice by microinjection of plasmid vector or ribonucleoprotein into zygotes. We also investigated whether single amino-acid-substituted mice and conditional knockout mice could be generated. Founder mice bearing base substitutions were generated more efficiently by co microinjection of Cas9 protein, a guide RNA and single-stranded oligodeoxynucleotide (ssODN) than by plasmid microinjection with ssODN. The conditional allele was successfully introduced by the one-step insertion of an ssODN designed to carry an exon flanked by two loxP sequences and homology arms using a double-cut CRISPR-Cas9 strategy. Our study presents a useful method for the CRISPR-Cas9-based generation of genetically modified mice from the viewpoints of animal welfare and work efficiency. PMID- 27387533 TI - Plasmodium AdoMetDC/ODC bifunctional enzyme is essential for male sexual stage development and mosquito transmission. AB - Polyamines are positively-charged organic molecules that are important for cellular growth and division. Polyamines and their synthesizing enzymes are particularly abundant in rapidly proliferating eukaryotic cells such as parasitic protozoa and cancer cells. Polyamine biosynthesis inhibitors, such as Elfornithine, are now being considered for cancer prevention and have been used effectively against Trypanosoma brucei Inhibitors of polyamine biosynthesis have caused growth arrest of Plasmodium falciparum blood stages in vitro, but in P. berghei only partial inhibition has been observed. While polyamine biosynthesis enzymes are characterized and conserved in Plasmodium spp., little is known on the biological roles of these enzymes inside malaria parasite hosts. The bifunctional polyamine biosynthesis enzyme S-adenosyl methionine decarboxylase/ornithine decarboxylase (AdoMetDC/ODC) was targeted for deletion in P. yoelii Deletion of AdoMetDC/ODC significantly reduced blood stage parasitemia but Anopheles transmission was completely blocked. We showed that male gametocytogenesis and male gamete exflagellation were abolished and consequently no ookinetes or oocyst sporozoites could be generated from adometdc/odc(-) parasites. Supplementation of putrescine and spermidine did not rescue the defective phenotypes of male gametocytes and gametes of the knockout parasites. These results highlight the crucial role of polyamine homeostasis in the development and functions of Plasmodium erythrocytic stages in the blood and in the mosquito vector and validate polyamine biosynthesis pathway enzymes as drug targeting candidates for malaria parasite transmission blocking. PMID- 27387534 TI - Probing extracellular Sonic hedgehog in neurons. AB - The bioactivity of Sonic hedgehog (Shh) depends on specific lipid modifications; a palmitate at its N-terminus and a cholesterol at its C-terminus. This dual lipid modification makes Shh molecules lipophilic, which prevents them from diffusing freely in extracellular space. Multiple lines of evidence indicate that Shh proteins are carried by various forms of extracellular vesicles (EVs). It also has been shown, for instance, that in some tissues Shh proteins are transported to neighboring cells directly via filopodia. We have previously reported that Shh proteins are expressed in hippocampal neurons. In this study we show that, in the hippocampus and cerebellum of postnatal day (P)2 rats, Shh is mostly found near or on the membrane surface of small neurites or filopodia. We also examined cultured hippocampal neurons where we observed noticeable and widespread Shh-immunolabeled vesicles located outside neurons. Through immunoelectron microscopy and biochemical analysis, we find Shh-containing EVs with a wide range of sizes. Unlike robust Shh activity in EVs isolated from cells overexpressing an N-terminal Shh fragment construct, we did not detect measurable Shh activity in EVs purified from the medium of cultured hippocampal neurons. These results suggest the complexity of the transcellular Shh signaling mechanisms in neurons. PMID- 27387535 TI - Gait in ducks (Anas platyrhynchos) and chickens (Gallus gallus) - similarities in adaptation to high growth rate. AB - Genetic selection for increased growth rate and muscle mass in broiler chickens has been accompanied by mobility issues and poor gait. There are concerns that the Pekin duck, which is on a similar selection trajectory (for production traits) to the broiler chicken, may encounter gait problems in the future. In order to understand how gait has been altered by selection, the walking ability of divergent lines of high- and low-growth chickens and ducks was objectively measured using a pressure platform, which recorded various components of their gait. In both species, lines which had been selected for large breast muscle mass moved at a slower velocity and with a greater step width than their lighter conspecifics. These high-growth lines also spent more time supported by two feet in order to improve balance when compared with their lighter, low-growth conspecifics. We demonstrate that chicken and duck lines which have been subjected to intense selection for high growth rates and meat yields have adapted their gait in similar ways. A greater understanding of which components of gait have been altered in selected lines with impaired walking ability may lead to more effective breeding strategies to improve gait in poultry. PMID- 27387537 TI - Ginsenosides Rg3 attenuates glucocorticoid-induced osteoporosis through regulating BMP-2/BMPR1A/Runx2 signaling pathway. AB - Glucocorticoid-induced osteoporosis (GIOP) is the primary cause of secondary osteoporosis and the existing therapeutic strategies are limited. The aim of this study is to evaluate the effects of ginsenosides (GS) Rg3 on dexamethasone (DEX) induced osteoporosis in vivo and in vitro. GIOP rat was established by DEX injection for 5 weeks and treated by GS Rg3 10 or 20 mg/kg. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment. Histological changes of femurs were observed using HE staining. The in vitro model was established on primary osteoblasts induced by DEX. CCK-8 assay was used to test the cell viability. Bone metabolism markers in serum or primary osteoblasts were detected using biochemical kits. Real time PCR and western blot were used to measure nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), bone morphogenic protein-2 (BMP-2), BMP receptor 1A (BMPR1A) and Runx2 expression. The results demonstrated that GS Rg3 prevented DEX-induced body weight and BMD reduction, enhanced secretion of bone formation markers and decreased bone resorption markers. In addition, GS Rg3 was found to prevent the suppression of BMP-2/BMPR1A/Runx2 signals induced by DEX both in GIOP rats and primary osteoblasts. Inhibition of BMP-2 by noggin completely blocked the bone alkaline phosphatase-secretion-promoted effect of GS Rg3 in vitro. These data suggest that GS Rg3 attenuates GIOP through regulating BMP-2 signaling pathway. This study provides a potential drug candidate for GIOP therapy. PMID- 27387536 TI - Rational design of carbon nitride photocatalysts by identification of cyanamide defects as catalytically relevant sites. AB - The heptazine-based polymer melon (also known as graphitic carbon nitride, g C3N4) is a promising photocatalyst for hydrogen evolution. Nonetheless, attempts to improve its inherently low activity are rarely based on rational approaches because of a lack of fundamental understanding of its mechanistic operation. Here we employ molecular heptazine-based model catalysts to identify the cyanamide moiety as a photocatalytically relevant 'defect'. We exploit this knowledge for the rational design of a carbon nitride polymer populated with cyanamide groups, yielding a material with 12 and 16 times the hydrogen evolution rate and apparent quantum efficiency (400 nm), respectively, compared with the unmodified melon. Computational modelling and material characterization suggest that this moiety improves coordination (and, in turn, charge transfer kinetics) to the platinum co catalyst and enhances the separation of the photogenerated charge carriers. The demonstrated knowledge transfer for rational catalyst design presented here provides the conceptual framework for engineering high-performance heptazine based photocatalysts. PMID- 27387538 TI - Enantioselective inhibition of Cytochrome P450-mediated drug metabolism by a novel antithrombotic agent, S002-333: Major effect on CYP2B6. AB - A significant number of new chemical entities (NCEs) fail in drug discovery due to inhibition of Cytochrome P450 (CYP) enzymes. Therefore, to avert costly drug failure at the clinical phase it becomes indispensable to evaluate the CYP inhibition profile of NCEs early in drug discovery. In light of these concerns, we envisioned to investigate the inhibitory effects of S002-333 [2-(4-methoxy benzenesulfonyl)-2,3,4,9-tetrahydro-1H-b-carboxylic acid amide], a novel and potent antithrombotic agent, on nine major CYP enzymes (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4) of human liver microsomes (HLM). S002-333 exists as racemic mixture of S004-1032 (R-isomer) and S007-1558 (S-isomer), consequently, we further examined the enantioselective differences of S002-333 in the inhibition of human CYP enzymes. Of the CYP enzymes tested, CYP2B6-catalyzed bupropion 6-hydroxylation was inhibited by S002-333 (IC50 ~ 9.25 +/- 2.46 MUM) in a stereoselective manner with (S)-isomer showing potent inhibition (IC50 ~ 5.28 +/- 1.25 MUM) in contrast to (R)-isomer which showed negligible inhibition on CYP2B6 activity (IC50 > 50 MUM). S002-333 and its (S)-isomer inhibited CYP2B6 activity in a non-competitive fashion with estimated Ki values of 10.1 +/- 3.4 MUM and 5.09 +/- 1.05 MUM, respectively. No shift in the IC50 value was observed for S002-333 and its isomers when preincubated for 30 min in the presence of NADPH suggesting that neither S002-333 nor its enantiomers are time-dependent inhibitors. Thus, the present findings signified that S002-333 is a potent stereoselective inhibitor of CYP2B6, whereas, inhibition for other CYPs was substantially negligible. These in vitro findings would be useful in deciding the development of S002-333 as a single-enantiomer or as a racemic mixture. PMID- 27387539 TI - The immature rat as a potential model for chemical risks to children: Ontogeny of selected hepatic P450s. AB - Concern about potential susceptibilities of infants and children to chemicals has led to the consideration of immature rodents as potential test surrogates. Maturation of some hepatic microsomal cytochrome P450s (CYPs), that participate in metabolic activation of organic solvents and polycyclic aromatic hydrocarbons (PAHs), may differ significantly between humans and rodents. The present investigation was undertaken to delineate the ontogeny of selected hepatic CYPs in male and female Sprague-Dawley (S-D) rats, and to contrast them with developmental profiles in humans. Microsomes were prepared from the liver of sexed and unsexed postnatal day (PND) 1-90 rats, and total CYP450 levels, as well as CYP1A1/2, CYP2E1 and CYP2B1/2 activities and protein, were quantified. CYP1A1/2 and CYP2E1 activity and expression rose rapidly after birth, peaked from PND 21-40/50, and declined substantially to adult values by PND 90. The same ontogenic profiles were manifested when the enzyme activities were expressed per entire liver or liver normalized to body weight. CYP1A1/2 and CYP2E1 activity and protein expression were well correlated. CYP2B1/2 activity peaked abruptly on PND 21 and declined irregularly to adult values. These patterns are in contrast to human CYP1A2 and CYP2E1, which are reported to progressively increase in liver during the first few months to years of life. The three CYP protein developmental profiles were largely gender independent in rats. The immature rat does not appear to be a suitable model for assessing risks posed to infants and children by chemicals metabolically activated by CYP2E1, based on the findings of greater carbon tetrachloride hepatotoxicity in preweanlings and weanlings than in adult animals. Additional studies are required to determine whether immature S-D rats may be used as an animal model for substrates of other CYPs, as total CYP450 levels in the liver progressively rose during maturation, similarly to humans. PMID- 27387540 TI - Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX. AB - Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy. PMID- 27387541 TI - Modulation of paraoxonase 1 (PON1) activity and protein N-homocysteinylation by bisphosphonates in rats. AB - BACKGROUND AND AIM: Bisphosphonates are potent antiresorptive agents commonly used in the treatment of osteoporosis. As osteoporosis and atherosclerosis share some common risk factors and frequently coexist in the same patients, we examined the effect of bisphosphonates on paraoxonase 1 (PON1) - the high density lipoprotein-associated enzyme with potent anti-atherosclerotic activity. MATERIAL AND METHODS: Bisphosphonates were administered orally to male adult rats for 4 weeks and then PON1 activity and some related biochemical parameters were measured in plasma. RESULTS: Clodronate, alendronate, ibandronate and pamidronate reduced PON1 activity toward synthetic (paraoxon, phenyl acetate) and natural (homocysteine thiolactone) substrates. The most marked effect was observed in animals receiving ibandronate. In contrast, risedronate increased PON1 activity toward these 3 substrates and zoledronate increased PON1 activity toward phenyl acetate but had no effect on its activity toward paraoxon and homocysteine thiolactone. Bisphosphonates had no effect on total plasma homocysteine and protein-bound homocysteine thiolactone. In addition, total plasma cholesterol, HDL-cholesterol, plasma triglycerides and alanine aminotransferase activity did not differ between groups. CONCLUSIONS: Bisphosphonates have differential effects on PON1 activity. Risedronate could be particularly useful in patients with high cardiovascular risk and PON1 deficiency. Bisphosphonates have no effect on plasma homocysteine and protein N-homocysteinylation as well as on the lipid profile. PMID- 27387543 TI - The use of simple physiological and environmental measures to estimate the latent heat transfer in crossbred Holstein cows. AB - The aim of the present study was to estimate the heat transfer through cutaneous and respiratory evaporation of dairy cows raised in tropical ambient conditions using simple environmental and physiological measures. Twenty-six lactating crossbred cows (7/8 Holstein-Gir) were used, 8 predominantly white and 18 predominantly black. The environmental variables air temperature, relative humidity, black globe temperature, and wind speed were measured. Respiratory rate and coat surface temperature were measured at 0700, 0900, 1100, 1300, and 1500 h. The environmental and physiological data were used to estimate heat loss by respiratory (ER) and cutaneous evaporation (EC). Results showed that there was variation (P < 0.01) for respiratory rate depending on the times of the day. The highest values were recorded at 1100, 1300, and 1500 h, corresponding to 66.85 +/ 10.20, 66.98 +/- 7.80, and 65.65 +/- 6.50 breaths/min, respectively. Thus, the amount of heat transferred via respiration ranged from 19.21 to 29.42 W/m2. There was a variation from 31.6 to 38.8 degrees C for coat surface temperature; these values reflected a range of 55.52 to 566.83 W/m2 for heat transfer via cutaneous evaporation. However, throughout the day, the dissipation of thermal energy through the coat surface accounted for 87.9 % total loss of latent heat, and the remainder (12.1 %) was via the respiratory tract. In conclusion, the predictive models based on respiratory rate and coat surface temperature may be used to estimate the latent heat loss in dairy cows kept confined in tropical ambient conditions. PMID- 27387542 TI - A biology-driven receptor model for daily pollen allergy risk in Korea based on Weibull probability density function. AB - Pollen is an important cause of respiratory allergic reactions. As individual sanitation has improved, allergy risk has increased, and this trend is expected to continue due to climate change. Atmospheric pollen concentration is highly influenced by weather conditions. Regression analysis and modeling of the relationships between airborne pollen concentrations and weather conditions were performed to analyze and forecast pollen conditions. Traditionally, daily pollen concentration has been estimated using regression models that describe the relationships between observed pollen concentrations and weather conditions. These models were able to forecast daily concentrations at the sites of observation, but lacked broader spatial applicability beyond those sites. To overcome this limitation, an integrated modeling scheme was developed that is designed to represent the underlying processes of pollen production and distribution. A maximum potential for airborne pollen is first determined using the Weibull probability density function. Then, daily pollen concentration is estimated using multiple regression models. Daily risk grade levels are determined based on the risk criteria used in Korea. The mean percentages of agreement between the observed and estimated levels were 81.4-88.2 % and 92.5 98.5 % for oak and Japanese hop pollens, respectively. The new models estimated daily pollen risk more accurately than the original statistical models because of the newly integrated biological response curves. Although they overestimated seasonal mean concentration, they did not simulate all of the peak concentrations. This issue would be resolved by adding more variables that affect the prevalence and internal maturity of pollens. PMID- 27387544 TI - Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units. AB - BACKGROUND: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. METHODS: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH >= 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. RESULTS: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 +/- 7.2 and 19 +/- 5.8 for the ACPE patients (p < 0.05), 20 +/- 5.7 and 19 +/- 5.1 for the COPD patients (p < 0.01) and 18 +/- 5.9 and 17 +/- 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 +/- 22 and 70 +/- 15 in the ACPE patients (p < 0.001), 87 +/- 21 and 76 +/- 14 in the COPD patients, and 83 +/- 17 and 74 +/- 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 +/- 3.1 vs. 3.6 +/- 2.5, NS; COPD, 5.1 +/- 3 vs. 3.6 +/- 2.1, p < 0.001; and OHS, 4.3 +/- 2.6 vs. 3.7 +/- 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. CONCLUSIONS: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH <= 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria. PMID- 27387545 TI - Comment on "Regulation of immunity during visceral Leishmania infection" and further discussions about the role of antibodies in infections with Leishmania. AB - Comments on the article "Regulation of immunity during visceral Leishmania infection" published in Parasites & Vectors 2016, 9:118, and further discussions about the role of antibodies in infections with Leishmania. PMID- 27387547 TI - Incidence and determinants of medication errors and adverse drug events among hospitalized children in West Ethiopia. AB - BACKGROUND: Medication errors cause a large number of adverse drug events with negative patient health outcomes and are a major public-health burden contributing to 18.7-56 % of all adverse drug events among hospitalized patients. The aim of this study was to assess the incidence and determinants of medication errors and adverse drug events among hospitalized children. METHODS: A prospective observational study was conducted among hospitalized children in the pediatrics ward of Nekemte Referral Hospital from February 24 to March 28, 2014. Data were collected by using checklist guided observation and review of medication order sheets, medication administration records, and other medical charts of the patients. To identify the independent predictors of medication errors and adverse drug events, backward logistic regression analysis was used. Statistical significance was considered at p-value <0.05. RESULTS: Out of 233 patients who were included in the study, 175 (75.1 %) of patients were exposed to medication errors. From the 1,115 medication orders reviewed, 513 (46.0 %) medication errors, 75 (6.7 %) potential adverse drug events and 17 (1.5 %) actual adverse drug events were identified. Of the 17 adverse drug events, eight (47.0 %) were preventable while nine (53.0 %) were not. Most medication errors were dosing errors (118; 23.0 %), followed by wrong drug (109; 21.2 %) and wrong time of administration (79; 15.4 %). On multivariable logistic regression analysis, length of hospital stay of >= 5 days (AOR = 4.2, 95 % CI = 1.7-10.4, p = 0.002), and number of medication of 4-6 (AOR = 4.9, 95 % CI = 2.3-10.3, p < 0.001) and number of medication of >=7 (AOR = 10.4, 95 % CI = 3.0-35.9, p < 0.001) were independent predictors of medication errors; and length of hospital stay of >= 5 days (AOR = 3.5, 95 % CI = 1.2-10.1, p = 0.023) and number of disease conditions =2 (AOR = 4.6, 95 % CI = 1.4-15.1, p = 0.014) were independent predictors of adverse drug events. CONCLUSION: Medication errors and adverse drug events are common on the pediatrics ward of Nekemte Referral Hospital. In particular, children with multiple medications and longer hospital stays, and those with co morbidities and longer hospital stays, were at greater risk for medication errors and adverse drug events, respectively. PMID- 27387546 TI - Mammographic density and structural features can individually and jointly contribute to breast cancer risk assessment in mammography screening: a case control study. AB - BACKGROUND: Mammographic density is a well-established risk factor for breast cancer. We investigated the association between three different methods of measuring density or parenchymal pattern/texture on digitized film-based mammograms, and examined to what extent textural features independently and jointly with density can improve the ability to identify screening women at increased risk of breast cancer. METHODS: The study included 121 cases and 259 age- and time matched controls based on a cohort of 14,736 women with negative screening mammograms from a population-based screening programme in Denmark in 2007 (followed until 31 December 2010). Mammograms were assessed using the Breast Imaging-Reporting and Data System (BI-RADS) density classification, Tabar's classification on parenchymal patterns and a fully automated texture quantification technique. The individual and combined association with breast cancer was estimated using binary logistic regression to calculate Odds Ratios (ORs) and the area under the receiver operating characteristic (ROC) curves (AUCs). RESULTS: Cases showed significantly higher BI-RADS and texture scores on average than controls (p < 0.001). All three methods were individually able to segregate women into different risk groups showing significant ORs for BI-RADS D3 and D4 (OR: 2.37; 1.32-4.25 and 3.93; 1.88-8.20), Tabar's PIII and PIV (OR: 3.23; 1.20-8.75 and 4.40; 2.31-8.38), and the highest quartile of the texture score (3.04; 1.63-5.67). AUCs for BI-RADS, Tabar and the texture scores (continuous) were 0.63 (0.57-0-69), 0.65 (0.59-0-71) and 0.63 (0.57-0-69), respectively. Combining two or more methods increased model fit in all combinations, demonstrating the highest AUC of 0.69 (0.63-0.74) when all three methods were combined (a significant increase from standard BI-RADS alone). CONCLUSION: Our findings suggest that the (relative) amount of fibroglandular tissue (density) and mammographic structural features (texture/parenchymal pattern) jointly can improve risk segregation of screening women, using information already available from normal screening routine, in respect to future personalized screening strategies. PMID- 27387548 TI - Continuum of Care Services for Maternal and Child Health using mobile technology a health system strengthening strategy in low and middle income countries. AB - BACKGROUND: Mobile phone technology is utilized for better delivery of health services worldwide. In low-and-middle income countries mobile phones are now ubiquitous. Thus leveraging mHealth applications in health sector is becoming popular rapidly in these countries. To assess the effectiveness of the Continuum of Care Services (CCS) mHealth platform in terms of strengthening the delivery of maternal and child health (MCH) services in a district in Bihar, a resource-poor state in India. METHODS: The CommCare mHealth platform was customized to CCS as one of the innovations under a project funded by the Bill and Melinda Gates Foundation to improve the maternal and newborn health services in Bihar. The intervention was rolled out in one project district in Bihar, during July 2012. More than 550 frontline workers out of a total of 3000 including Accredited Social Health Activists, Anganwadi Workers, Auxilliary Nurse Midwives and Lady Health Supervisors were trained to use the mHealth platform. The service delivery components namely early registration of pregnant women, three antenatal visits, tetanus toxoid immunization of the mother, iron and folic acid tablet supply, institutional delivery, postnatal home visits and early initiation of breastfeeding were used as indicators for good quality services. The resultant coverage of these services in the implementation area was compared with rest of Bihar and previous year statistics of the same area. The time lag between delivery of a service and its record capture in the maternal and child tracking system (MCTS) database was computed in a random sample of 16,000 beneficiaries. The coverage of services among marginalized and non-marginalized castes was compared to indicate equity of service delivery. Health system strengthening was viewed from the angle of coverage, quality, equity and efficiency of services. RESULTS: The implementation blocks had higher coverage of all the eight indicator services compared to rest of Bihar and the previous year. There was equity of services across castes for all the indicators. Timely capture of data was also ensured compared to paper-based reporting. CONCLUSION: By virtue of its impact on quality, efficiency and equity of service delivery, health care manpower efficiency and governance, the mHealth inclusion at service provision level can be one of the potential strategy to strengthen the health system. PMID- 27387549 TI - Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 to 2014. AB - BACKGROUND: To determine the impact of the introduction of artemisinin-based combination therapy (ACT) on parasite susceptibility, a molecular surveillance for antimalarial drug resistance was conducted on local isolates from the Hopital Principal de Dakar between November 2013 and January 2014 and between August 2014 and December 2014. METHODS: The prevalence of genetic polymorphisms in antimalarial resistance genes (pfcrt, pfmdr1, pfdhfr and pfdhps) was evaluated in 103 isolates. RESULTS: The chloroquine-resistant haplotypes CVIET and CVMET were identified in 31.4 and 3.9 % of the isolates, respectively. The frequency of the pfcrt K76T mutation was increased from 29.3 % in 2013-2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr triple mutant (S108N, N51I and C59R) was detected in the majority of the isolates (82.3 %). The prevalence of quadruple mutants (pfdhfr S108N, N51I, C59R and pfdhps A437G) was 40.4 %. One isolate (1.1 %) harboured the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, N51I and C59R. CONCLUSIONS: Despite a decline in the prevalence of chloroquine resistance due to the official withdrawal of the drug and to the introduction of ACT, the spread of resistance to chloroquine has continued. Furthermore, susceptibility to amodiaquine may be decreased as a result of cross-resistance. The frequency of the pfmdr1 mutation N86Y declined while the Y184F mutation increased in prevalence, suggesting that selective pressure is acting on pfmdr1, leading to a high prevalence of mutations in these isolates and the lack of specific mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and Y184F suggests a decrease in lumefantrine susceptibility. Based on these results, intensive surveillance of ACT partner drugs must be conducted regularly in Senegal. PMID- 27387552 TI - The architecture of neutrophil extracellular traps investigated by atomic force microscopy. AB - Neutrophils are immune cells that engage in a suicidal pathway leading to the release of partially decondensed chromatin, or neutrophil extracellular traps (NETs). NETs behave as a double edged sword; they can bind to pathogens thereby ensnaring them and limiting their spread during infection; however, they may bind to host circulating materials and trigger thrombotic events, and are associated with autoimmune disorders. Despite the fundamental role of NETs as part of an immune system response, there is currently a very poor understanding of how their nanoscale properties are reflected in their macroscopic impact. In this work, using a combination of fluorescence and atomic force microscopy, we show that NETs appear as a branching filament network that results in a substantially organized porous structure with openings with 0.03 +/- 0.04 MUm(2) on average and thus in the size range of small pathogens. Topological profiles typically up to 3 +/- 1 nm in height are compatible with a "beads on a string" model of nucleosome chromatin. Typical branch lengths of 153 +/- 103 nm appearing as rigid rods and height profiles of naked DNA in NETs of 1.2 +/- 0.5 nm are indicative of extensive DNA supercoiling throughout NETs. The presence of DNA duplexes could also be inferred from force spectroscopy and the occurrence of force plateaus that ranged from ~65 pN to 300 pN. Proteolytic digestion of NETs resulted in widespread disassembly of the network structure and considerable loss of mechanical properties. Our results suggest that the underlying structure of NETs is considerably organized and that part of its protein content plays an important role in maintaining its mesh architecture. We anticipate that NETs may work as microscopic mechanical sieves with elastic properties that stem from their DNA protein composition, which is able to segregate particles also as a result of their size. Such a behavior may explain their participation in capturing pathogens and their association with thrombosis. PMID- 27387550 TI - Impact of the Mycobaterium africanum West Africa 2 Lineage on TB Diagnostics in West Africa: Decreased Sensitivity of Rapid Identification Tests in The Gambia. AB - BACKGROUND: MPT64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (TB). Mycobacterium africanum West Africa 2 (Maf 2) remains an important cause of TB in West Africa and causes one third of disease in The Gambia. Since the introduction of MPT64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (NTM) was seen among AFB smear positive TB suspects, which led us to prospectively assess sensitivity of the MPT64 antigen test in our setting. METHODOLOGY/PRINCIPAL FINDINGS: We compared the abundance of mRNA encoded by the mpt64 gene in sputa of patients with untreated pulmonary TB caused by Maf 2 and Mycobacterium tuberculosis (Mtb). Subsequently, prospectively collected sputum samples from presumptive TB patients were inoculated in the BACTEC MGIT 960 System. One hundred and seventy-three acid fast bacilli (AFB)-positive and blood agar negative MGIT cultures were included in the study. Cultures were tested on the day of MGIT positivity with the BD MGIT TBc Identification Test. A random set of positives and all negatives were additionally tested with the SD Bioline Ag MPT64 Rapid. MPT64 negative cultures were further incubated at 37 degrees C and retested until positive. Bacteria were spoligotyped and assigned to different lineages. Maf 2 isolates were 2.52-fold less likely to produce a positive test result and sensitivity ranged from 78.4% to 84.3% at the beginning and end of the recommended 10 day testing window, respectively. There was no significant difference between the tests. We further showed that the decreased rapid test sensitivity was attributable to variations in mycobacterial growth behavior and the smear grades of the patient. CONCLUSIONS/SIGNIFICANCE: In areas where Maf 2 is endemic MPT64 tests should be cautiously used and MPT64 negative results confirmed by a second technique, such as nucleic acid amplification tests, to avoid their misclassification as NTMs. PMID- 27387551 TI - Classical V600E and other non-hotspot BRAF mutations in adult differentiated thyroid cancer. AB - BACKGROUND: BRAF is the most frequently mutated gene in differentiated thyroid cancer (DTC). Previous studies on DTC have well documented high rates of the BRAF (V600E) mutation in patients of mixed ages. Previous studies either included a mix of pediatric and adult patients or pediatric patients only. However, the prevalence of hotspot and non-hotspot BRAF mutations and its significance in pure adult DTCs is not yet well determined. In this study we determine the frequency of this classical BRAF mutation and other rare BRAF mutations in pure adult DTCs. METHODS: A total of 204 adult DTC samples (Age >18 years) were analyzed for mutations in exon 15 of the BRAF gene by performing polymerase chain reaction (PCR) amplification of tumor genomic DNAs and direct sequencing of amplicons using Sanger sequencing. Obtained results were correlated to clinical and pathological characteristics of DTCs. Statistical analyses were performed using SPSS (The Statistical Package for Social Sciences) version 20 software. RESULTS: Overall, BRAF mutations were identified in 48.5 % (99/204) of adult DTCs. Three rare non-hotspot mutations (T599I, T599dup and K601E) were detected in four tumor samples (2 %). One (K601E) of these non-hotspot mutations occurred in conventional papillary thyroid cancer (CPTC) and other three (T599I, T599dup and K601E) were found in follicular variant PTC. We found significant association between BRAF (V600E) mutation and age (P < 0.0001), extrathyroidal invasion (P = 0.017), lymph node metastasis (P = 0.038) and TNM stage III/IV (P = 0.001). CONCLUSIONS: Our study is the first to report BRAF mutations in a pure adult sample of DTCs of Saudi Arabian ethnicity. Our results show a high rate and a strong prognostic role of the classical BRAF (V600E) mutation and also suggest a common occurrence of non-hot spot mutations in adult DTC from this highly inbred population. PMID- 27387553 TI - Self-rating of daily time management in children: psychometric properties of the Time-S. AB - BACKGROUND: Impaired ability to manage time has been shown in several diagnoses common in childhood. Impaired ability involves activities and participation domain (daily time management, DTM) and body function and structure domain (time processing ability, TPA). DTM needs to be evaluated from an individual's own perspective. To date, there has been a lack of self-rating instruments for children that focus on DTM. AIM: The aim of this study is to describe psychometric properties of Time-S when used in children aged 10-17 years with a diagnosis of ADHD, Autism, CP or mild ID. Further, to test whether TPA correlates with self-rated DTM. MATERIAL AND METHODS: Eighty-three children aged 10-17 years participated in the study. Rasch analysis was used to assess psychometric properties. Correlation analysis was performed between Time-S and a measure of TPA. RESULTS: The 21 items of the Time-S questionnaire fit into a unitary construct measuring self-perceived daily management of an individual's time. A non-significant, small correlation was found between TPA and DTM. CONCLUSION AND SIGNIFICANCE: The results indicate good psychometric properties for the questionnaire. The questionnaire is potentially useful in intervention planning and evaluation. PMID- 27387554 TI - The influence of dysfunctional impulsivity and alexithymia on aggressive behavior of psychiatric patients. AB - Current approaches in Dutch mental health care institutions towards inpatients' aggression have focused predominantly on environmental factors, such as training the staff in aggression management. However, personality traits might be an important factor in patients' aggression - as shown by incidents in the wards. This study explores the influence of dysfunctional impulsivity and alexithymia on psychiatric patients' aggressive behavior, through self-reports and through involvement in aggressive incidents. Personality traits influencing patients' aggression emphasize the importance of a more direct approach to their aggression. Clinical patients at Dutch mental health care institution Emergis (n=84) filled out questionnaires about their aggressiveness (using Buss and Perry's Aggression Questionnaire Short Form), dysfunctional impulsivity and alexithymia. Multiple regression analyses indicated that dysfunctional impulsivity positively related to self-reported aggressive behavior. The relationship, however, could not be confirmed for inpatients' aggression as reported by the staff on the wards. Unexpectedly affective alexithymia negatively related to hostility. Gender differences in self-reported aggression were found. Female patients showed higher levels of hostility. Regression analyses indicated that the male gender positively related to physical aggression. Findings emphasize the importance of a new approach in Dutch mental health care, in which patients may engage in aggression-regulation training programs. PMID- 27387555 TI - Schisandra chinensis produces the antidepressant-like effects in repeated corticosterone-induced mice via the BDNF/TrkB/CREB signaling pathway. AB - The present study aimed to examine the antidepressant-like effects and the possible mechanisms of Schisandra chinensis on depressive-like behavior induced by repeated corticosterone injections in mice. Here we evaluated the effect of an ethanol extract of the dried fruit of S. chinensis (EESC) on BDNF/TrkB/CREB signaling in the hippocampus and the prefrontal cortex. Three weeks of corticosterone injections in mice resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase the immobility time in the forced swim test, but without any influence on the locomotor activity. Further, there was a significant increase in serum corticosterone level and a significant downregulation of BDNF/TrkB/CREB signaling pathway in the hippocampus and prefrontal cortex in CORT-treated mice. Treatment of mice with EESC (600mg/kg) significantly ameliorated all the behavioral and biochemical changes induced by corticosterone. Moreover, pharmacological inhibition of BDNF signaling by K252a abolished entirely the antidepressant-like effect triggered by chronic EESC treatment. These results suggest that EESC produces an antidepressant-like effect in CORT-induced depression in mice, which is possibly mediated, at least in part, by rectifying the stress-based hypothalamic-pituitary-adrenal (HPA) axis dysfunction paradigm and upregulation of BDNF/TrkB/CREB signaling pathway. PMID- 27387556 TI - Double hexagonal graphene ring synthesized using a growth-etching method. AB - Precisely controlling the layer number, stacking order, edge configuration, shape and structure of graphene is extremely challenging but highly desirable in scientific research. In this report, a new concept named the growth-etching method has been explored to synthesize a graphene ring using the chemical vapor deposition process. The graphene ring is a hexagonal structure, which contains a hexagonal exterior edge and a hexagonal hole in the centre region. The most important concept introduced here is that the oxide nanoparticle derived from annealing is found to play a dual role. Firstly, it acts as a nucleation site to grow the hexagonal graphene domain and then it works as a defect for etching to form a hole. The evolution process of the graphene ring with the etching time was carefully studied. In addition, a double hexagonal graphene ring was successfully synthesized for the first time by repeating the growth-etching process, which not only confirms the validity and repeatability of the method developed here but may also be further extended to grow unique graphene nanostructures with three, four, or even tens of graphene rings. Finally, a schematic model was drawn to illustrate how the double hexagonal graphene ring is generated and propagated. The results shown here may provide valuable guidance for the design and growth of unique nanostructures of graphene and other two-dimensional materials. PMID- 27387557 TI - Kinesiophobia and its relation to pain characteristics and cognitive affective variables in older adults with chronic pain. AB - BACKGROUND: The contribution of kinesiophobia (fear of movement) to the pain experience among older adults has been poorly evaluated. The aim of this study was to study prevalence at baseline, development over a 12-month period and cognitive-affective variables of kinesiophobia in a population-based sample of older adults with chronic pain. METHODS: The study included 433 older adults (+65 years) with chronic pain (mean age 74.8 years) randomly selected using a Swedish register of inhabitants. Kinesiophobia was measured at baseline and 12-month follow-up with the 11-item version of the Tampa Scale of Kinesiophobia (TSK-11). Associations of demographic-, cognitive affective - and pain-related variables to kinesiophobia were analysed with linear regression analyses. RESULTS: The mean level of kinesiophobia was low. Worsening and recovering from kinesiophobia occurred over time, but the mean level of kinesiophobia remained unchanged (p = 0.972). High levels of kinesiophobia (TSK >=35) were found among frailer and older adults predominately living in care homes, but not dependent on sex. Poor self-perceived health (OR = 8.84) and high pain intensity (OR = 1.22) were significantly associated with kinesiophobia. CONCLUSION: Results indicate that potential interventions regarding kinesiophobia among older adults should aim to decrease pain intensity and strengthen health beliefs. PMID- 27387558 TI - Efficient Computation of the Hartree-Fock Exchange in Real-Space with Projection Operators. AB - We describe an efficient projection-based real-space implementation of the nonlocal single-determinant exchange operator. Through a matrix representation of the projected operator, we show that this scheme works equally well for both occupied and virtual states. Our scheme reaches a speedup of 2 orders of magnitude and has no significant loss of accuracy compared to an implementation of the full nonlocal single-determinant exchange operator. We find excellent agreement upon comparing Hartree-Fock eigenvalues, dipoles, and polarizabilities of selected molecules calculated using our method to values in the literature. To illustrate the efficiency of this scheme we perform calculations on systems with up to 240 carbon atoms. PMID- 27387560 TI - LEON-BIS: multiple alignment evaluation of sequence neighbours using a Bayesian inference system. AB - BACKGROUND: A standard procedure in many areas of bioinformatics is to use a multiple sequence alignment (MSA) as the basis for various types of homology based inference. Applications include 3D structure modelling, protein functional annotation, prediction of molecular interactions, etc. These applications, however sophisticated, are generally highly sensitive to the alignment used, and neglecting non-homologous or uncertain regions in the alignment can lead to significant bias in the subsequent inferences. RESULTS: Here, we present a new method, LEON-BIS, which uses a robust Bayesian framework to estimate the homologous relations between sequences in a protein multiple alignment. Sequences are clustered into sub-families and relations are predicted at different levels, including 'core blocks', 'regions' and full-length proteins. The accuracy and reliability of the predictions are demonstrated in large-scale comparisons using well annotated alignment databases, where the homologous sequence segments are detected with very high sensitivity and specificity. CONCLUSIONS: LEON-BIS uses robust Bayesian statistics to distinguish the portions of multiple sequence alignments that are conserved either across the whole family or within subfamilies. LEON-BIS should thus be useful for automatic, high-throughput genome annotations, 2D/3D structure predictions, protein-protein interaction predictions etc. PMID- 27387561 TI - Allergic contact dermatitis to topical prodrugs used in photodynamic therapy. PMID- 27387559 TI - GSK-3 directly regulates phospho-4EBP1 in renal cell carcinoma cell-line: an intrinsic subcellular mechanism for resistance to mTORC1 inhibition. AB - BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin 1 (mTORC1) signaling pathway is aberrantly activated in renal cell carcinoma (RCC). We previously demonstrated glycogen synthase kinase-3beta (GSK 3beta) positively regulated RCC proliferation. The aim of this study was to evaluate the role of GSK-3 in the PI3K/Akt/mTORC1 pathway and regulation of the downstream substrates, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), ribosomal protein S6 kinase (S6K), and ribosomal protein S6 (S6RP). METHODS: We used human RCC cell lines (ACHN, Caki1, and A498) and, as normal controls, human renal proximal tubular epithelial cell (HRPTEpC) and non tumorous kidney tissues that were obtained surgically for treatment of RCC patients. Rapamycin-resistant ACHN (ACHN/RR) cells were generated with chronic exposure of ACHN to rapamycin ranging from 1nM finally to 1 MUM. Cell viability, cell cycling and direct interaction between GSK-3beta and 4EBP1 were evaluated with MTS assay, flowcytometry and in vitro kinase assay with recombinant GSK 3beta and 4EBP1products, respectively. Protein expression and phosphorylation of molecules associated with the PI3K/Akt/mTORC1 pathway were examined by immunoblotting. Effects of drug combination were determined as the combination index with CompuSyn software. RESULTS: Overexpression and phosphorylation of 4EBP1 and S6RP together with GSK-3 activation were observed in RCC cell lines, but not in human normal kidney cells and tissues. Cell proliferation, p4EBP1 and pS6RP were strongly suppressed by GSK-3 inhibition. Rapamycin and LY294002 sufficiently decreased pS6RP, but only moderately p4EBP1. In vitro kinase assays showed that recombinant GSK-3beta phosphorylated recombinant 4EBP1, and the effect was blocked by GSK-3 inhibitors. Different from rapamycin, AR- A014418 remarkably inhibited cell proliferation, and rapidly suppressed p4EBP1 and pS6RP in ACHN and ACHN/RR (in 30 min to 1 h). AR- A014418 and rapamycin combination showed additivity at lower concentrations, but antagonism at higher concentrations. CONCLUSIONS: GSK-3beta could directly phosphorylate 4EBP1 and activate the mTORC1 downstream signaling cascades to enhance protein biosynthesis and cell proliferation in RCC cell lines independent of rapamycin sensitivity. The direct GSK-3beta/4EBP1 pathway might be an important subcellular mechanism as an inherent equipment for RCC cells to acquire clinical chemoresistance to mTORC1 inhibitors. PMID- 27387562 TI - Maker Cultures and the Prospects for Technological Action. AB - Supported by easier and cheaper access to tools and expanding communities, maker cultures are pointing towards the ideas of (almost) everyone designing, creating, producing and distributing renewed, new and improved products, machines, things or artefacts. A careful analysis of the assumptions and challenges of maker cultures emphasizes the relevance of what may be called technological action, that is, active and critical interventions regarding the purposes and applications of technologies within ordinary lives, thus countering the deterministic trends of current directions of technology. In such transformative potential, we will explore a set of elements what is and could be technological action through snapshots of maker cultures based on the empirical research conducted in three particular contexts: the Fab Lab Network, Maker Media core outputs and initiatives such as Maker Faires, and the Open Source Hardware Association (OSHWA). Elements such as control and empowerment through material engagement, openness and sharing, and social, cultural, political and ethical values of the common good in topics such as diversity, sustainability and transparency, are critically analysed. PMID- 27387563 TI - What Rights Do Authors Have? PMID- 27387565 TI - The diagnostic utility of 3D-ESI rotating and moving dipole methodology in the pre-surgical evaluation of MRI-negative childhood epilepsy due to focal cortical dysplasia. AB - OBJECTIVE: This study investigates whether a combined rotating dipole (RD) and moving dipole (MD) solution enhances three-dimensional electroencephalography (EEG) source imaging (3D-ESI) localization in magnetic resonance imaging (MRI) negative pediatric patients with focal cortical dysplasia (FCD). METHODS: We retrospectively selected 14 MRI-negative patients with FCD from a cohort of 60 pediatric patients previously used to evaluate the diagnostic utility of 3D-ESI in epilepsy surgery. Patients were younger than 18 years at time of surgery and had at least 1 year of outcome data. RD and MD models were constructed for each interictal spike or sharp wave, and it was determined whether each inverse algorithm localized within the surgical resection cavity (SRC). We also compared the 3D-ESI findings and surgical outcome with positron emission tomography (PET) and ictal single photon emission computed tomography (iSPECT). RESULTS: RD analyses revealed a high concordance with the SRC (78.6%), particularly for temporal lobe resection (100.0%), and showed superior localization compared to PET and iSPECT, with the highest correlation in FCD type I and temporal lobe resection. Furthermore, the RD method was superior to iSPECT in FCD type II cases and to PET in extratemporal resections. RD and MD results were comparable, but in 18.2% of patients with FCD type I with localizing RDs, the MD solution was only partially within the SRC; in all of these patients 3D-ESI also correlated with superior surgical outcome compared to PET and iSPECT, especially when RD and MD solutions were analyzed together. SIGNIFICANCE: 3D-ESI in MRI-negative cases showed superior localization compared to iSPECT or PET, especially in FCD type I and temporal lobe epilepsy, and correlated with superior surgical outcome compared to iSPECT and PET at 1 year and 2 years postoperatively, especially when RD and MD solutions were analyzed together. These findings suggest that 3D-ESI based on a combined RD-MD solution improves surgical accuracy in MRI-negative patients with FCD. PMID- 27387566 TI - Long-Term Outcomes of the Boston Type I Keratoprosthesis in the Management of Corneal Limbal Stem Cell Deficiency. AB - PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (KPro) in the management of limbal stem cell deficiency (LSCD). METHODS: Retrospective review of KPro procedures performed by a single surgeon from May 1, 2004, to January 1, 2015. RESULTS: One hundred seventy-three KPro procedures were performed in 149 eyes, including 68 in 54 eyes with LSCD. Glaucoma (48% vs. 82%, P < 0.0001) and a history of >=2 keratoplasties (39% vs. 79%, P < 0.0001) were significantly less common in eyes with LSCD. Preoperative corrected distance visual acuity was >=20/200 in 7% of eyes with LSCD and 9% of eyes without LSCD. A significantly greater percentage of eyes with LSCD had CDVA >= 20/200 at each of the first 5 years after surgery. The only postoperative complication more common in eyes with LSCD compared with eyes without was persistent corneal epithelial defect (50% vs. 28%, P = 0.013), although the associated secondary complications sterile corneal necrosis (22% vs. 11%, P = 0.059) and corneal infiltrate (20% vs. 10%, P = 0.08) were twice as common in eyes with LSCD. Despite this, the retention failure rates in eyes with and without LSCD were similar (0.089/eye-yr vs. 0.071/eye-yr; P = 0.53). CONCLUSIONS: Boston type I keratoprosthesis implantation results in a significant improvement in CDVA in the majority of eyes with LSCD through 5 years after surgery, with better visual outcomes than eyes without LSCD. Although several postoperative complications are more common in LSCD, sight-threatening complications such as endophthalmitis and retinal detachment are not. Additionally, there is no difference in the retention failure rate in eyes with and without LSCD, although a larger number of procedures with longer follow-up will be needed to determine retention outcomes more than 5 years after surgery. PMID- 27387564 TI - Review of Instructional Approaches in Ethics Education. AB - Increased investment in ethics education has prompted a variety of instructional objectives and frameworks. Yet, no systematic procedure to classify these varying instructional approaches has been attempted. In the present study, a quantitative clustering procedure was conducted to derive a typology of instruction in ethics education. In total, 330 ethics training programs were included in the cluster analysis. The training programs were appraised with respect to four instructional categories including instructional content, processes, delivery methods, and activities. Eight instructional approaches were identified through this clustering procedure, and these instructional approaches showed different levels of effectiveness. Instructional effectiveness was assessed based on one of nine commonly used ethics criteria. With respect to specific training types, Professional Decision Processes Training (d = 0.50) and Field-Specific Compliance Training (d = 0.46) appear to be viable approaches to ethics training based on Cohen's d effect size estimates. By contrast, two commonly used approaches, General Discussion Training (d = 0.31) and Norm Adherence Training (d = 0.37), were found to be considerably less effective. The implications for instruction in ethics training are discussed. PMID- 27387567 TI - Influence of Posterior Corneal Astigmatism on Total Corneal Astigmatism in Eyes With Keratoconus. AB - PURPOSE: To measure posterior corneal astigmatism (PCA) and investigate its influence on total corneal astigmatism (TCA) in eyes with keratoconus. METHODS: Keratometric astigmatism (KA), PCA, and TCA were investigated by means of a dual Scheimpflug analyzer in patients with keratoconus. Vector analysis was carried out with the Naeser polar value method. RESULTS: We enrolled 119 eyes. PCA magnitude averaged 0.77 +/- 0.43 diopters (D) and exceeded 0.50, 1.00, and 2.00 D in 73.9%, 21.8%, and 16.8% of eyes, respectively. PCA averaged 0.95 +/- 0.48, 0.55 +/- 0.28, and 0.70 +/- 0.35 D in eyes with with-the-rule (WTR), against-the rule (ATR), and oblique astigmatism. The steepest posterior meridian was oriented vertically (between 61 and 119 degrees) in 55.5% of eyes, thus generating ATR astigmatism. The difference between the location of the steepest meridian of KA and that of TCA was >10 degrees in 8.4% of eyes. On average, KA overestimated TCA in eyes with WTR astigmatism by 0.16 D and underestimated TCA in eyes with ATR astigmatism by 0.22 D. The PCA power oriented along the steeper anterior corneal meridian averaged -0.83 +/- 0.40, -0.40 +/- 0.37, and -0.53 +/- 0.43 D for WTR, ATR, and obliquely astigmatic eyes, respectively. Linear regression disclosed a statistically significant correlation (P < 0.0001, r = 0.16) between the meridional powers of TCA and PCA. CONCLUSIONS: In eyes with keratoconus, PCA displays large, variable values and is correlated to TCA. The influence of PCA on TCA cannot be disregarded when planning astigmatism correction by toric intraocular lenses. PMID- 27387568 TI - Re: Arvola R. P., Robciuc A., Holopainen J. M. Matrix Regeneration Therapy: A Case Series of Corneal Neurotrophic Ulcers. PMID- 27387569 TI - Intra-Subject Consistency and Reliability of Response Following 2 mA Transcranial Direct Current Stimulation. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a popular non invasive brain stimulation technique that has been shown to influence cortical excitability. While polarity specific effects have often been reported, this is not always the case, and variability in both the magnitude and direction of the effects have been observed. OBJECTIVE/HYPOTHESIS: We aimed to explore the consistency and reliability of the effects of tDCS by investigating changes in cortical excitability across multiple testing sessions in the same individuals. A within subjects design was used to investigate the effects of anodal and cathodal tDCS applied to the motor cortex. Four experimental sessions were tested for each polarity in addition to two sham sessions. METHODS: Transcranial magnetic stimulation (TMS) was used to measure cortical excitability (TMS recruitment curves). Changes in excitability were measured by comparing baseline measures and those taken immediately following 20 minutes of 2 mA stimulation or sham stimulation. RESULTS: Anodal tDCS significantly increased cortical excitability at a group level, whereas cathodal tDCS failed to have any significant effects. The sham condition also failed to show any significant changes. Analysis of intra subject responses to anodal stimulation across four sessions suggest that the amount of change in excitability across sessions was only weakly associated, and was found to have poor reliability across sessions (ICC = 0.276). The effects of cathodal stimulation show even poorer reliability across sessions (ICC = 0.137). In contrast ICC analysis for the two sessions of sham stimulation reflect a moderate level of reliability (ICC = .424). CONCLUSIONS: Our findings indicate that although 2 mA anodal tDCS is effective at increasing cortical excitability at group level, the effects are unreliable across repeated testing sessions within individual participants. Our results suggest that 2 mA cathodal tDCS does not significantly alter cortical excitability immediately following stimulation and that there is poor reliability of the effect within the same individual across different testing sessions. PMID- 27387570 TI - Re: "Renal Carcinoid Tumor Metastatic to the Uvea, Medial Rectus Muscle, and the Contralateral Lacrimal Gland". PMID- 27387571 TI - Reply re: "Renal Carcinoid Tumor Metastatic to the Uvea, Medial Rectus Muscle, and the Contralateral Lacrimal Gland". PMID- 27387572 TI - Fornix Reduction for Treatment of Giant Fornix Syndrome. PMID- 27387573 TI - Re: "Histopathology and Immunophenotyping of Congenital Lacrimal (Anlage) Fistulae". PMID- 27387574 TI - Reply re: "Histopathology and Immunophenotyping of Congenital Lacrimal (Anlage) Fistulae". PMID- 27387575 TI - Re: "One-Stage Alternatives to the Hughes Procedure for Reconstruction of Large Lower Eyelid Defects: Surgical Techniques and Outcomes". PMID- 27387576 TI - Modification of a Minimally Invasive Conjunctivodacryocystorhinostomy With Jones Tube Placement. PMID- 27387577 TI - Crystal Structures, Stabilities, Electronic Properties, and Hardness of MoB2: First-Principles Calculations. AB - On the basis of the first-principles techniques, we perform the structure prediction for MoB2. Accordingly, a new ground-state crystal structure WB2 (P63/mmc, 2 fu/cell) is uncovered. The experimental synthesized rhombohedral R3m and hexagonal AlB2, as well as theoretical predicted RuB2 structures, are no longer the most favorite structures. By analyzing the elastic constants, formation enthalpies, and phonon dispersion, we find that the WB2 phase is thermodynamically and mechanically stable. The high bulk modulus B, shear modulus G, low Poisson's ratio nu, and small B/G ratio are benefit to its low compressibility. When the pressure is 10 GPa, a phase transition is observed between the WB2-MoB2 and the rhombohedral R3m MoB2 phases. By analyzing the density of states and electron density, we find that the strong covalent is formed in MoB2 compounds, which contributes a great deal to its low compressibility. Furthermore, the low compressibility is also correlated with the local buckled structure. PMID- 27387580 TI - To love, wisdom, and the personal in practice. PMID- 27387578 TI - PI3 Kinase Pathway Mutations in Human Cancers. PMID- 27387581 TI - Putting the new NICE menopause guideline into practice. PMID- 27387582 TI - Young parents' views and experiences of interactions with health professionals. AB - BACKGROUND: Although teenage pregnancy levels are declining, the North East of England still has the highest rate of young parenthood (age <18 years) in the UK. Young parents and their children often face many health and social problems, requiring interactions with a wide range of health professionals, such as midwives, doctors and health visitors. AIM: This qualitative interview study aimed to explore young parents' views and experiences of interactions with health professionals. METHODS: Young mothers and fathers (n=10) were recruited from youth groups and Sure Start parenting classes in Newcastle upon Tyne during the period April-June 2013. They took part in one-to-one or small group semi structured interviews regarding their experiences of interacting with health professionals about their own health and that of their child. The interviews were transcribed and analysed using thematic content analysis. RESULTS: Emergent themes included: beliefs about children's health; proving oneself as a parent; and positives of parenting. All the participants distinguished between being a 'first-time parent, not just a young parent' and all, to varying degrees, challenged the authority and judgement of medical and nursing practitioners with regard to their children's health. CONCLUSIONS: The findings of this study highlight the need for health professionals to be particularly aware of the sensitivities arising from the power imbalances perceived by young parents of ill children. This can be achieved by following communication skills frameworks (e.g. the Calgary-Cambridge framework) that emphasise the importance of techniques such as active listening and building rapport. PMID- 27387583 TI - Commentary on 'Young parents' views and experiences of interactions with health professionals': tools for engaging and supporting teenage parents to improve their lives. PMID- 27387584 TI - Living the Life Unexpected: 12 Weeks to Your Plan B for a Meaningful and Fulfilling Future Without Children: Other Than Mother Choosing Childlessness with Life in Mind. PMID- 27387585 TI - Personal reflections on the menopause journey. PMID- 27387587 TI - Venus. PMID- 27387586 TI - Increased body mass index and reduced efficacy of oral emergency contraception: how many women might be affected? PMID- 27387588 TI - Plastic surgery in the Norwegian undergraduate medical curriculum: students' knowledge and attitudes. A nationwide case-control study. AB - OBJECTIVE: Changes in medical education have resulted in less available time for plastic surgery, which might jeopardise the availability of plastic surgery for patients. The aims of this study were to investigate the level of knowledge within and attitudes towards plastic surgery among medical students, and find predictors for a wish to pursue a career in plastic surgery. METHODS: A previously used questionnaire was sent to all clinical medical students. Law students were used as a control group. RESULTS: Thirty per cent of all clinical medical students in the country responded. The majority of students considered education in plastic surgery valuable/very valuable and 23% were considering it as a career. Nonetheless, about half of the students were unaware of the plastic surgical education at their faculty and reported non-academic sources of learning. Only 44% of medical students were able to name five common plastic surgical procedures and 8% were unable to name any. Law students were superior to medical students in the task (p = 0.005). Forty-two per cent of medical students were successful in indicating on which body parts plastic surgeons operate, whereas law students were less successful (p = 0.001). Male gender and positive valuing of clinical attachment could predict a wish for a career in plastic surgery. CONCLUSION: In some aspects, medical students are only as knowledgeable as their non-medical peers. These results call for higher quality plastic surgery teaching, to secure referral of the correct patients and successful specialist recruitment to plastic surgery. PMID- 27387589 TI - [Quality of life and schizophrenia: Which evaluation scale for which quality of life?]. AB - The concept of quality of life is an old one, but used extensively in the literature since the 90s with a growing number of instruments. Such diversity makes it difficult for clinicians to choose the most appropriate one regarding their divergence on different aspects including how to use them (especially self questionnaire versus clinician based semi-structure interview), for what aim (from cost perspective, to functionality and/or subjective well-beingness), relying on what dimensions (as the covered quality of life dimensions are not always overlapping), and in which clinical settings (especially according to the availability or not of trained clinicians, and depending of the available time for such assessments). The aim of the literature review is to describe the most frequently used and/or quoted quality of life instruments in schizophrenia, and to describe their different characteristics and specificities in order to help clinicians to find the most appropriate one according to expectancies, possibilities and interests. In this review, we were able to collect 23 instruments, which need between 3 and 60min to fill-in, are relying in between 5 and 146 items, and allowing the assessment of 1 to 14 different quality of life dimensions. The two extremes could be the EuroQOL, which only has 5 self-report questions (with a visual analogical scale, for the rating procedure) and therefore needing only a couple of minutes, and the Quality of Life Scale which needs an initial training for quotation, relies on a semi-structured interview screening 21 items that are used to assess four different dimensions. Because of the heterogeneity of the broad concept of quality of life, and especially the diversity of the expectancies of the different instruments, it is not surprising that so many instruments are being proposed. But this statement reinforces the requirement that clinicians use the most adequate one, not only according to the expectancies, but also taking into account the local possibilities, especially regarding time to fill in the instrument and the possibility for clinicians to be trained if needed. PMID- 27387590 TI - Effectiveness of critical care pathways for head and neck cancer surgery: A systematic review. AB - BACKGROUND: Critical care pathways (CCPs) are implemented within health care systems as a means to systematically decrease resource utilization, whereas maintaining a high level of care for patients with a specific diagnosis. Previous studies have shown equivocal results for CCPs in head and neck cancer surgery. METHODS: We conducted a systematic review evaluating studies of CCPs for head and neck cancer surgery, with individual outcome measures analyzed separately to describe the effect of each implemented pathway. RESULTS: Ten before and after studies were included for systematic review. Nine reported statistically significant decreases in median/mean length of stay and 5 reported statistically significant decreases in cost of care per case. CONCLUSION: Although the results are encouraging and point toward the ability of CCPs to decrease length of stay and cost of care, the evidence cannot be considered exhaustive because of the studies' inability to account for temporal trends. Further controlled studies are recommended to validate the benefits of CCPs. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1421-1427, 2016. PMID- 27387591 TI - Serial multiple crossed immunoelectrophoresis at a microscale: A stamp-sized 2D immunoanalysis of protein C3 activation caused by nanoparticles. AB - Crossed immunoelectrophoresis (C-IE) is used to detect and quantify specific proteins. An application allowed the evaluation of complement system activation by nanomaterials. The work aimed to improve the C-IE toward a higher throughput and less tedious method. A new concept was implemented to prepare and run agarose gels. The first and the second dimension of electrophoresis were performed on a single gel plate, prepared before the beginning of the analysis. Several samples were migrated simultaneously on the same migration line. Up to 35 analyses were run at once, providing stamp-sized electrophoregrams (2.8 * 3 cm(2) ) maintaining the performance of the original method performed on 5 * 7 cm(2) gel slabs. Robustness and precision of the method were demonstrated through a validation approach using ANOVA. Handling, experimental duration, amount of reagents, and overall cost of one analysis were considerably reduced compared to the original method. With the same equipment, seven times more analyses can be performed in one run. C-IE can be used to analyze many types of proteins. The new experimental modalities were suitable for the application developed in the present work that was to evaluate activation of protein C3 of the complement system triggered by nanomaterials. PMID- 27387593 TI - Serine Protease Catalysis: A Computational Study of Tetrahedral Intermediates and Inhibitory Adducts. AB - Peptide boronic acids and peptidyl trifluoromethyl ketones (TFKs) inhibit serine proteases by forming monoanionic, tetrahedral adducts to serine in the active sites. Investigators regard these adducts as analogs of monoanionic, tetrahedral intermediates. Density functional theory (DFT) calculations and fractional charge analysis show that tetrahedral adducts of model peptidyl TFKs are structurally and electrostatically very similar to corresponding tetrahedral intermediates. In contrast, the DFT calculations show the structures and electrostatic properties of analogous peptide boronate adducts to be significantly different. The peptide boronates display highly electrostatically positive boron, with correspondingly negative ligands in the tetrahedra. In addition, the computed boron-oxygen and boron-carbon bond lengths in peptide boronates (which are identical or very similar to the corresponding bonds in a peptide boronate adduct of alpha-lytic protease determined by X-ray crystallography at subangstrom resolution) are significantly longer than the corresponding bond lengths in model tetrahedral intermediates. Since protease-peptidyl TFKs incorporate low-barrier hydrogen bonds (LBHBs) between an active site histidine and aspartate, while the protease peptide boronates do not, these data complement the spectroscopic and chemical evidence for the participation of LBHBs in catalysis by serine proteases. Moreover, while the potency of these classes of inhibitors can be correlated to the structures of the peptide moieties, the present results indicate that the strength of their bonds to serine contribute significantly to their inhibitory properties. PMID- 27387592 TI - Identification of Wet-Spinning and Post-Spin Stretching Methods Amenable to Recombinant Spider Aciniform Silk. AB - Spider silks are outstanding biomaterials with mechanical properties that outperform synthetic materials. Of the six fibrillar spider silks, aciniform (or wrapping) silk is the toughest through a unique combination of strength and extensibility. In this study, a wet-spinning method for recombinant Argiope trifasciata aciniform spidroin (AcSp1) is introduced. Recombinant AcSp1 comprising three 200 amino acid repeat units was solubilized in a 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP)/water mixture, forming a viscous alpha-helix enriched spinning dope, and wet-spun into an ethanol/water coagulation bath allowing continuous fiber production. Post-spin stretching of the resulting wet spun fibers in water significantly improved fiber strength, enriched beta-sheet conformation without complete alpha-helix depletion, and enhanced birefringence. These methods allow reproducible aciniform silk fiber formation, albeit with lower extensibility than native silk, requiring conditions and methods distinct from those previously reported for other silk proteins. This provides an essential starting point for tailoring wet-spinning of aciniform silk to achieve desired properties. PMID- 27387595 TI - Base-Catalyzed Hydrophosphination of Azobenzenes with Diarylphosphine Oxides: A Precise Construction of N-N-P Unit. AB - Addition of diarylphosphine oxides to the N?N double bond of azobenzenes leads to the formation of the P-substituted hydrazines in up to 98% yield for 24 examples, and the formation of diphenylphosphinic amides was observed in three substrates. This strategy features tolerance of a wide range of functional groups, simple operation, and mild reaction conditions. Specially, this method can be also applied to the gram-scale synthesis of the product. A polar reaction mechanism is also proposed based on control experiments. PMID- 27387594 TI - Effect of caesarean section on maternal and foetal outcomes in acute fatty liver of pregnancy: a systematic review and meta-analysis. AB - Several studies have reported a positive association between caesarean section for expeditious pregnancy termination and perinatal outcomes in acute fatty liver of pregnancy (AFLP); however, the risks remain unclear and independent studies have reported conflicting findings. In this meta-analysis, we aimed to confirm the relationship between caesarean section and perinatal outcomes in AFLP. The PubMed, Embase, and China National Knowledge Infrastructure databases were searched (until July 17, 2015) for observational clinical studies focusing on the association between caesarean section and perinatal outcomes in AFLP. Data were extracted and processed independently by 2 authors. We also compared caesarean section with vaginal delivery to further investigate this relationship. We observed that 2 of the 3 primary outcomes in caesarean section exhibited positive effects-the maternal mortality rate was 44% lower (relative risk [RR], 0.56 [0.41 0.76]) and perinatal mortality rate was also reduced (RR, 0.52 [0.38-0.71]), compared to those for vaginal delivery. We did not find any associations between caesarean section and perinatal outcomes in AFLP in terms of neonatal mortality type and maternal multiple organ complications. These findings emphasise the significant prognostic value and clinical implications of caesarean section in AFLP, and suggest that the adverse outcomes should be reduced. PMID- 27387596 TI - Lewis acid catalyzed [2+2] cycloaddition of ynamides and propargyl silyl ethers: synthesis of alkylidenecyclobutenones and their reactivity in ring-opening and ring expansion. AB - A family of four-membered enones, polysubstituted alkylidenecyclobutenones, were easily prepared by a Lewis acid catalyzed [2+2] cycloaddition of ynamides and propargyl silyl ethers. This challenging regioselective [2+2] cycloaddition enables the efficient construction and conversion of four-membered enones, which provides high-value and structurally diverse products through the unexpected ring opening and ring expansion of alkylidenecyclobutenone with Grignard reagents, organolithium, primary amines, and water. PMID- 27387597 TI - Neural Stem Cells and Nutrients: Poised Between Quiescence and Exhaustion. AB - Adult neurogenesis initiated by neural stem cells (NSCs) contributes to brain homeostasis, damage repair, and cognition. Energy metabolism plays a pivotal role in neurogenic cell fate decisions regarding self-renewal, expansion and multilineage differentiation. NSCs need to fine-tune quiescence and proliferation/commitment to guarantee lifelong neurogenesis and avoid premature exhaustion. Accumulating evidence supports a model whereby calorie restriction or increased energy expenditure reinforce NSC quiescence and promote self-renewal. Conversely, growth/proliferation inputs and anabolic signals, although necessary for neurogenesis, deplete the NSCs pool in the long run. This framework incorporates the emerging neurogenic roles of nutrient-sensing signaling pathways, providing a rationale for the alarming connection between nutritional imbalances, metabolic disorders and accelerated brain aging. PMID- 27387598 TI - The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis. AB - Epidemiological studies link fructose consumption with metabolic disease, an association attributable in part to fructose-mediated lipogenesis. The mechanisms governing fructose-induced lipogenesis and disease remain debated. Acutely, fructose increases de novo lipogenesis through the efficient and uninhibited action of ketohexokinase and aldolase B which yields substrates for fatty-acid synthesis. Chronic fructose consumption further enhances the capacity for hepatic fructose metabolism by activating several key transcription factors (i.e., SREBP1c and ChREBP) which augment the expression of lipogenic enzymes, increasing lipogenesis and further compounding hypertriglyceridemia and hepatic steatosis. Hepatic insulin resistance develops from diacylglycerol-PKCE-mediated impairment of insulin signaling and possibly additional mechanisms. Initiatives that decrease fructose consumption and therapies that block fructose-mediated lipogenesis will be necessary to avert future metabolic pandemics. PMID- 27387600 TI - A chemical synthesis of a multiply 13 C-labeled hexasaccharide: a high-mannose N glycan fragment. AB - As covalent modifiers of proteins, high-mannose N-glycans are important in maintaining protein structure and function in vivo. The conformations of these glycans can be studied by nuclear magnetic resonance spectroscopy using spin-spin couplings (J-couplings; scalar couplings) and other nuclear magnetic resonance parameters that are sensitive to the geometries of their constituent glycosidic linkages and other mobile elements in their structures. These analyses often require 13 C-labeling at specific carbon atoms, especially when measurements of 13 C-13 C J-couplings are of interest. The selection of particular 13 C isotopomers of a glycan depends on the type of question under scrutiny. A chemical synthesis of a mannose-containing hexasaccharide, alpha[1-13 C]Man(1 >2)alpha[1,2-13 C2 ]Man(1->6)[alpha[1-13 C]Man(1->2)alpha[1,2-13 C2 ]Man(1 >3)]alpha[1,2-13 C2 ]Man(1->6)betaManOCH3 , which is a nested fragment of the high-mannose N-glycans of human glycoproteins and contains eight 13 C-enriched carbon sites, is described in this report. The selected 13 C isotopomer was chosen to maximize the measurement of J-couplings sensitive to linkage conformations. This work demonstrates that chemical syntheses of multiply 13 C labeled oligosaccharides are technically feasible and practical using present synthetic methods. The availability of this and other multiply 13 C-labeled mannose-containing oligosaccharides will promote future studies of their conformations in solution and in the bound state. PMID- 27387599 TI - Neuroimaging of translocator protein in patients with systemic lupus erythematosus: a pilot study using [11C]DPA-713 positron emission tomography. AB - : Objective Inflammation secondary to autoantibody-mediated effects occurring in multiple organs is a hallmark of systemic lupus erythematosus (SLE). The inflammatory response to SLE-mediated damage in brain parenchyma has been postulated in both normal and cognitively impaired individuals. Our goal is to use molecular imaging to investigate the distribution within the brain of the mitochondrial translocator protein (TSPO) that is upregulated during glial cell activation, and is considered as a marker of brain injury and repair. Methods We sought to characterize TSPO distribution in the brain of SLE patients using positron emission tomography (PET) and [11C]DPA-713 (DPA), a radiopharmaceutical that targets TSPO. We imaged 11 healthy controls and 10 patients with SLE (years of diagnosis: 13.0 +/- 7.7), all between the ages of 22 and 52. RESULTS: Among the nine brain regions studied, no statistically significant increases in DPA binding were observed in SLE. Instead, there was a significant decrease in TSPO distribution in the cerebellum and hippocampus of SLE patients, as compared to healthy controls. Such decreases were most significant in cognitively normal SLE subjects, but showed pseudo-normalization in those with cognitive impairment, due to higher cerebellar and hippocampal DPA binding in the cognitively impaired (versus normal) SLE brain. Conclusions Results from this pilot study suggest a link between diminished regional TSPO expression in the brain of patients with SLE, as well as possible glial cell activation within the cerebellum and hippocampus of cognitively impaired individuals with SLE. Further studies are needed to elucidate how mitochondrial dysfunction and glial cell activation may act together in SLE and SLE-mediated neurocognitive deficits. PMID- 27387602 TI - Rapid and Energy-Saving Microwave-Assisted Solid-State Synthesis of Pr(3+)-, Eu(3+)-, or Tb(3+)-Doped Lu2O3 Persistent Luminescence Materials. AB - Persistent luminescence materials Lu2O3:R(3+),M (Pr,Hf(IV); Eu; or Tb,Ca(2+)) were successfully and rapidly (22 min) prepared by microwave-assisted solid-state synthesis (MASS) using a carbon microwave susceptor and H3BO3 as flux. Reaction times are reduced by up to 93% over previous synthetic methods, without special gases application and using a domestic microwave oven. All materials prepared with H3BO3 flux exhibit LuBO3 impurities that were quantified by Rietveld refinement from synchrotron radiation X-ray powder diffraction patterns. The flux does not considerably affect the crystalline structure of the C-Lu2O3, however. Scanning electron micrographs suggest low surface area when H3BO3 flux is used in the materials' synthesis, decreasing the amount of surface hydroxyl groups in Lu2O3 and improving the luminescence intensity of the phosphors. The carbon used as the susceptor generates CO gas, leading to complete reduction of Tb(IV) to Tb(3+) and partial conversion of Pr(IV) to Pr(3+) present in the Tb4O7 and Pr6O11 precursors, as indicated by X-ray absorption near-edge structure data. Persistent luminescence spectra of the materials show the red/near-IR, reddish orange, and green emission colors assigned to the 4f(n) -> 4f(n) transitions characteristics of Pr(3+), Eu(3+), and Tb(3+) ions, respectively. Differences between the UV excited and persistent luminescence spectra can be explained by the preferential persistent luminescence emission of R(3+) ion in the S6 site rather than R(3+) in the C2 site. In addition, inclusion of Hf(IV) and Ca(2+) codopants in the Lu2O3 host increases the emission intensity and duration of persistent luminescence due to generation of traps caused by charge compensation in the lattice. Photonic materials prepared by MASS with H3BO3 flux show higher persistent luminescence performance than those prepared by the ceramic method or MASS without flux. Color tuning of persistent luminescence in Lu2O3:R(3+),M provides potential applications in bioimaging as well as in solar cell sensitizers. PMID- 27387601 TI - Immunoprotective effect of lentinan in combination with miltefosine on Leishmania infected J-774A.1 macrophages. AB - Rejuvenation of deteriorated host immune functions is imperative for successful annihilation of Leishmania parasites. The use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. We herein investigated the immunostimulatory potency of a beta-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on Leishmania-infected J-774A.1 macrophages. Our study shows that infected macrophages when stimulated with 2.5 MUg/mL and above concentrations of lentinan secreted significant amount of host-protective molecules. The in vitro interaction between lentinan and miltefosine showed some synergy (mean sum of fractional inhibitory concentration [mean ?FIC] 0.87) at IC50 level. Lentinan (2.5 MUg/mL) plus low-dose miltefosine (2 MUM) displayed heightened level of pro-inflammatory cytokines, IL-12 (13.6 fold) and TNF-alpha (6.8-fold) along with nitric oxide (7.2-fold higher) when compared with infected control. In combination group, we also observed remarkably (P<.001) suppressed levels of anti-inflammatory cytokines, IL-10 and TGF-beta, than that of untreated macrophages. Additionally, in comparison with infected group, we observed significant induction in phagocytic activity of macrophages in combination with treated group. Collectively, these findings emphasize the immunostimulatory effect of lentinan alone and in combination with low dose of miltefosine against Leishmania donovani. PMID- 27387603 TI - High Mobility MoS2 Transistor with Low Schottky Barrier Contact by Using Atomic Thick h-BN as a Tunneling Layer. AB - High-performance MoS2 transistors are developed using atomic hexagonal boron nitride as a tunneling layer to reduce the Schottky barrier and achieve low contact resistance between metal and MoS2 . Benefiting from the ultrathin tunneling layer within 0.6 nm, the Schottky barrier is significantly reduced from 158 to 31 meV with small tunneling resistance. PMID- 27387605 TI - 13C Metabolic Flux Analysis of acetate conversion to lipids by Yarrowia lipolytica. AB - Volatile fatty acids (VFAs) are an inexpensive and renewable carbon source that can be generated from gas fermentation and anaerobic digestion of fermentable wastes. The oleaginous yeast Yarrowia lipolytica is a promising biocatalyst that can utilize VFAs and convert them into triacylglycerides (TAGs). However, currently there is limited knowledge on the metabolism of Y. lipolytica when cultured on VFAs. To develop a better understanding, we used acetate as the sole carbon source to culture two strains, a control strain and a previously engineered strain for lipid overaccumulation. For both strains, metabolism during the growth phase and lipid production phase were investigated by metabolic flux analysis using two parallel sodium acetate tracers. The resolved flux distributions demonstrate that the glyoxylate shunt pathway is constantly active and the flux through gluconeogenesis varies depending on strain and phase. In particular, by regulating the activities of malate transport and pyruvate kinase, the cells divert only a portion of the glyoxylate shunt flux required to satisfy the needs for anaplerotic reactions and NADPH production through gluconeogenesis and the oxidative pentose phosphate pathway (PPP). Excess flux flows back to the tricarboxylic acid (TCA) cycle for energy production. As with the case of glucose as the substrate, the primary source for lipogenic NADPH is derived from the oxidative PPP. PMID- 27387604 TI - Phytohormone sensing in the biotrophic fungus Ustilago maydis - the dual role of the transcription factor Rss1. AB - The phenolic compound salicylic acid (SA) is a key signalling molecule regulating local and systemic plant defense responses, mainly against biotrophs. Many microbial organisms, including pathogens, share the ability to degrade SA. However, the mechanism by which they perceive SA is unknown. Here we show that Ustilago maydis, the causal agent of corn smut disease, employs a so far uncharacterized SA sensing mechanism. We identified and characterized the novel SA sensing regulator, Rss1, a binuclear zinc cluster protein with dual functions as putative SA receptor and transcriptional activator regulating genes important for SA and tryptophan degradation. Rss1 represents a major component in the identified SA sensing pathway during the fungus' saprophytic stage. However, Rss1 does not have a detectable impact on virulence. The data presented in this work indicate that alternative or redundant sensing cascades exist that regulate the expression of SA-responsive genes in U. maydis during its pathogenic development. PMID- 27387606 TI - Serotonin and poor neonatal adaptation after antidepressant exposure in utero. AB - OBJECTIVE: Infants exposed to selective antidepressants (SADs) in utero are at risk to develop poor neonatal adaptation (PNA) postpartum. As symptoms are non specific and the aetiology of PNA is unknown, the diagnostic process is hampered. We hypothesised that the serotonin metabolism plays a role in the aetiology of PNA. METHODS: In this controlled study, infants admitted postpartum from February 2012 to August 2013 were included and followed for 3 days. Infants exposed to SADs during at least the last 2 weeks of fetal life were included in the patient group (n=63). Infants not exposed to psychotropic medication and admitted postpartum for another reason were included in the control group (n=126). The neonatal urinary 5-hydroxyindoleacetid acid (5-HIAA) levels of SAD-exposed infants who developed PNA, SAD-exposed infants who did not develop PNA and control infants were compared. RESULTS: The course of the 5-HIAA levels over the first 3 days postpartum differed between infants with and without PNA (p<=0.001) with higher 5-HIAA levels in infants with PNA on day 1 (2.42 mmol/mol, p=0.001). Presence of maternal psychological distress modified this relationship. CONCLUSIONS: A transient disturbance of the neonatal serotonergic system may play a role in the aetiology of PNA. Other factors, including the presence of maternal psychological distress, also seem to play a role. PMID- 27387607 TI - Biodesalination-On harnessing the potential of nature's desalination processes. AB - Water scarcity is now one of the major global crises, which has affected many aspects of human health, industrial development and ecosystem stability. To overcome this issue, water desalination has been employed. It is a process to remove salt and other minerals from saline water, and it covers a variety of approaches from traditional distillation to the well-established reverse osmosis. Although current water desalination methods can effectively provide fresh water, they are becoming increasingly controversial due to their adverse environmental impacts including high energy intensity and highly concentrated brine waste. For millions of years, microorganisms, the masters of adaptation, have survived on Earth without the excessive use of energy and resources or compromising their ambient environment. This has encouraged scientists to study the possibility of using biological processes for seawater desalination and the field has been exponentially growing ever since. Here, the term biodesalination is offered to cover all of the techniques which have their roots in biology for producing fresh water from saline solution. In addition to reviewing and categorizing biodesalination processes for the first time, this review also reveals unexplored research areas in biodesalination having potential to be used in water treatment. PMID- 27387608 TI - Symptoms and quality of life in patients with chronic obstructive pulmonary disease treated with aclidinium in a real-life setting. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive disease with symptoms that can have a major impact on patients' physical health. The aim of this study was to evaluate quality of life (QoL), symptom severity and dyspnoea in COPD patients treated with aclidinium up to 24 weeks. METHODS: In this prospective non-interventional multicentre study (198 centres in Sweden, Denmark, and Norway), COPD patients (age >=40 years) who started treatment with aclidinium (initial therapy, change of treatment, or add-on therapy) could be included. Health-related QoL was obtained by COPD assessment test (CAT). Symptoms were evaluated on a 6-point Likert scale. The modified Medical Research Council (mMRC) Dyspnoea Scale was used as a simple grading system to assess the level of dyspnoea/shortness of breath from0 to 4. Patients on treatment with aclidinium who completed baseline and at least one follow-up visit (week 12 or 24) were included in the study population. RESULTS: Overall, 1,093 patients were enrolled (mean 69 years, 54% females), one-third had >=1 exacerbation the year prior to baseline. At enrolment, 48% were LAMA naive. Mean (standard deviation, SD) CAT score decreased from 16.9 (7.7) at baseline to 14.3 (7.3) at week 24 (p<0.01) with a decrease in all individual CAT items (p<0.05). Mean difference in morning and night-time symptoms from baseline to week 24 was -0.60 (SD 2.51) and -0.44 (SD 2.48), respectively (both p<0.001). Mean (SD) mMRC Dyspnoea Scale changed from 1.6 (1.0) at baseline to 1.5 (1.0) at week 24 (p<0.001). CONCLUSION: In this observational study of a Nordic real-life COPD population, treatment with aclidinium was associated with a clinically important improvement in QoL and morning and night-time symptoms, most pronounced in the LAMA naive group. However, there is still room for improvement in the management of symptomatic COPD patients. PMID- 27387609 TI - Exome sequencing a review of new strategies for rare genomic disease research. AB - The journey related to genomic information access and utilization by researchers and clinicians has barely begun to be travelled. There remains a broad horizon in the research and clinical arenas for fulfillment of that journey. Exciting is the potential depth and breadth of research, clinical applications, and more personalized medicine, that remain on the horizon. Exome sequencing has clarified the responsibilities of over 130 genes, greatly expanding the medical genetics database and enabling the development of orphan disease-based pharmaceuticals. Our research focus was to review >50 literature sources that related to rare genomic disease research and exome sequencing, as well as the new research and diagnostic strategies that were utilized. Using a systems approach, under discussion are ciliopathy, dermatology, otorhinolaryngology, immunology, gastroenterology, hematopoiesis, metabolic diseases, and the cardiovascular system. Also discussed are genetic, syndromic, and mitochondrial exome research. Recommendations for future research will also be discussed. PMID- 27387611 TI - Too few school nurses to tackle mental health crisis. AB - A continuing lack of nurses in schools will worsen the crisis in child mental health. PMID- 27387610 TI - Flagging up a tragic loss with a butterfly logo. AB - A simple idea from one patient has been turned into an initiative that it is hoped will be implemented in neonatal units up and down the UK. But it stemmed from one unintentional throwaway comment. PMID- 27387612 TI - Story in numbers. AB - Health checks for diabetes 2014-15. PMID- 27387613 TI - Children's diabetes testing falls short. AB - Three quarters of children aged 12 and older in England and Wales with diabetes did not have their recommended 7 health checks last year, although overall diabetes control rates have improved. PMID- 27387614 TI - Review finds nurses under too much pressure. AB - A review of paediatric intensive care services in England (PICU) is among 32 recommendations in the Independent Review of Children's Cardiac Services in Bristol. PMID- 27387615 TI - Butterfly logo may prevent needless upset for mothers. AB - A bereaved mother has devised a purple butterfly logo to be placed in neonatal unit cots to alert nurses and families that a baby from a multiple birth has died. PMID- 27387617 TI - RCN wants CPR training in schools. AB - Children should learn cardiopulmonary resuscitation (CPR) to equip them to save lives for the rest of their lives, politicians have been told. PMID- 27387622 TI - Knowledge of recovery position reduces hospital admission rate. AB - Campaigns to improve knowledge of the recovery position should be promoted to reduce the hospital admission rate of children who lose consciousness, say researchers. PMID- 27387618 TI - Has HEE got the balance between generic and specialist training right? AB - Health Education England's (HEE) long awaited response to the Shape of Caring review report Raising the Bar, leaves unanswered questions over the future of children's nurse training, but also room for debate. PMID- 27387623 TI - Expressing anger positively could reduce eating disorders. AB - Lessons on how to express anger in direct and positive ways could help reduce eating disorders in women and girls, say the authors of a new report. PMID- 27387624 TI - Neonatal jaundice. AB - Essential facts The National Institute for Health and Care Excellence (NICE) first published guidelines on jaundice in newborn babies in 2010 and updated them in May. Jaundice is caused by raised bilirubin levels when red blood cells are broken down. PMID- 27387625 TI - Accentuate the positive. AB - One of the joys of nursing is the variety, depending on your specialist field, and where you end up working. My sister is an adult nurse working in palliative care. We may share a job title but the day-to-day description of what we actually do could not be more different. PMID- 27387626 TI - Click - Self-harming. AB - Self-harming is the topic of this month's e-resource focus. PMID- 27387627 TI - Self Harm UK. AB - Part of Youthscape, Self Harm UK is a registered UK charity. In addition to explaining about self-harm, this website provides support aimed at young people. PMID- 27387628 TI - Achondroplasia. AB - Achondroplasia, like all syndromes, is recognised by a collection of typical anomalies. It is a cause of short stature; the average adult height being about 4 feet. PMID- 27387629 TI - How to apply for research ethics committee approval. AB - This article explores when and where ethical approval is required and how this should be undertaken. PMID- 27387630 TI - Inherited genetic conditions. AB - Background While it is known that early diagnosis leads to better health outcomes for children with inherited genetic conditions (IGCs) ( UK Newborn Screening Programme Centre 2012 , Bush 2008 ), families affected by IGCs face difficulties, including those associated with complex treatment regimens. PMID- 27387631 TI - Interventions needed to help families with inherited conditions. AB - The authors comment that this is the first intervention for facilitating better communication for families affected by, or at risk of, inherited genetic conditions (IGCs). Therefore the study provides an important contribution to the literature. PMID- 27387633 TI - An examination of interprofessional education in a pre-registration children's nursing course. AB - Aim This study set out to gain insight into views held by children's nursing students, lecturers and clinically based nurse mentors about interprofessional education (IPE). Method A qualitative research design was undertaken. Small focus groups were held with pre-registration children's nursing students, and semi structured interviews with university lecturers and clinically based nurse mentors to find out information about their understanding of IPE. Findings Participants not only valued IPE, but they agreed that it had the potential to positively affect the care of children, young people and their families. Conclusion It is important that professionals collaborate to ensure students receive high quality IPE learning experiences. PMID- 27387632 TI - Opioid consumption and bowel dysfunction in adolescents after spinal surgery. AB - The study, outlined in this article, aimed to ascertain the effect of length of surgery and opioid consumption on length of stay and bowel dysfunction, and to review current post-operative bowel practices. A retrospective case note review was carried out of all patients with a diagnosis of adolescent idiopathic scoliosis (n=44) who had undergone a posterior spinal fusion between January 2012 and May 2014. Mean length of surgery was 3:24 hours (+/-0:40 hours), while average length of stay was 6 days (mean 6.27 days +/-2.39). Average opioid consumption post-operatively was 152.15mg (+/-60.95mg). There were no statistically significant associations. Some form of laxative was received by 93% of (n=41) patients. Of those, 20 required an enema before discharge. This was most commonly administered on post-operative days four and five (65%). This service evaluation demonstrated that length of surgery and amount of opioid have no significant effect on length of stay for young people following a posterior spinal fusion. It is suggested that lactulose and senna are given in combination at doses as per the British National Formulary for Children starting on post operative day two, which should avoid the need to administer an enema. PMID- 27387634 TI - Adolescents' view and experiences of living with type 1 diabetes. AB - This literature review explores the perceptions and experiences of adolescents living with type 1 diabetes. The number of adolescents living with this condition is growing in Western societies. It is important to understand their views and experiences to ensure they receive optimum support. A systematic database search identified studies conducted between 2004 and 2014 undertaken in five countries. Most participants were aged 13-17 years, although some studies included participants aged 11-18 years. Key findings identified were: striving for autonomy; parental conflict; yearning for social acceptance; and concerns about diabetes education. Thematic analysis identified psychosocial, management, and knowledge of type 1 diabetes as the main themes. The review also identified that the psychosocial effects of living with type 1 diabetes were significant. Adolescents would benefit from more in-depth research on this subject and more innovative ways to help them cope better with their condition. PMID- 27387635 TI - Undertaking safe medicine administration with children: part 1. AB - This is the first of two articles that aim to provide children's nurses with an opportunity to develop their skills and knowledge of medicines management when caring for children and young people. This first article outlines the principles of effective medicines management including the pharmacology language required to accurately read prescriptions, the way children respond to medicines, managing risk, including the concept of human error, and working in partnership with children, young people and families. The second article, to be published in September, will focus on numeracy and calculation skills, identified as an important risk factor associated with medication errors in children. PMID- 27387636 TI - In other RCNi journals. AB - Mindfulness is a technique used in learning disability nursing practice to help people with a learning disability, and their carers, manage difficult emotions or situations. This article describes a workshop that introduced mindfulness practice to students. PMID- 27387637 TI - Recording practice related feedback for revalidation. AB - Get ready for revalidation 'Revalidation aims to increase public confidence that nurses and midwives are up to date in their practice'. PMID- 27387638 TI - Treatment and management of head injury in children. AB - Head injury is the most common cause of injury-related death and permanent disability in children. PMID- 27387639 TI - Depression in new fathers. AB - There is a growing awareness about the burden of ill-health experienced by men. Research has shown that fatherhood has a protective effect on men's health. However, the transition can be complex and demanding, and may cause distress, anxiety and increased risk of depression. This article discusses paternal postnatal depression, which is a significant public health issue that is not acknowledged widely or well researched. As a result, men are under-screened, under-diagnosed and under-treated for the condition and other postnatal mental health problems, causing detrimental effects on their health and negative effects on the health and wellbeing of mother and child. Read Paternal postnatal depression: an overview for primary healthcare professionals in Primary Health Care. PMID- 27387640 TI - Revalidation and mentorship. AB - Nurses and midwives who are registered with the Nursing and Midwifery Council (NMC) are required to renew their registration with the NMC. A new system of revalidation has now replaced post-registration education and practice standards and it is linked to the professional standards for nurses and midwives set out by the NMC and known as the Code. Mentorship is an essential part of the Code and will help registrants meet some or all of the requirements of revalidation. As registered nurses mentors will have to reflect on their practice and update their preparation for mentorship. This article provides guidance for mentors to help meet revalidation requirements. PMID- 27387641 TI - Therapeutic options in papillary thyroid carcinoma: current guidelines and future perspectives. AB - The treatment of papillary thyroid cancer is now based on individual patient risk and response to therapies. Molecular techniques are increasingly being used to risk stratify and to guide therapeutic decisions. There have been advances in the treatment of local disease through surgery or radioiodine. Directed techniques can target metastatic disease including bisphosphonates, radiofrequency ablation or radiotherapy. Systemic therapies such as tyrosine kinase inhibitors show great promise although such treatment must be individualized. Future therapies will target treating radioiodine refractory disease. PMID- 27387642 TI - Screening for plant viruses by next generation sequencing using a modified double strand RNA extraction protocol with an internal amplification control. AB - The majority of plant viruses contain RNA genomes. Detection of viral RNA genomes in infected plant material by next generation sequencing (NGS) is possible through the extraction and sequencing of total RNA, total RNA devoid of ribosomal RNA, small RNA interference (RNAi) molecules, or double stranded RNA (dsRNA). Plants do not typically produce high molecular weight dsRNA, therefore the presence of dsRNA makes it an attractive target for plant virus diagnostics. The sensitivity of NGS as a diagnostic method demands an effective dsRNA protocol that is both representative of the sample and minimizes sample cross contamination. We have developed a modified dsRNA extraction protocol that is more efficient compared to traditional protocols, requiring reduced amounts of starting material, that is less prone to sample cross contamination. This was accomplished by using bead based homogenization of plant material in closed, disposable 50ml tubes. To assess the quality of extraction, we also developed an internal control by designing a real-time (quantitative) PCR (qPCR) assay that targets endornaviruses present in Phaseolus vulgaris cultivar Black Turtle Soup (BTS). PMID- 27387643 TI - Neurofilament Light: A Dynamic Cross-Disease Fluid Biomarker for Neurodegeneration. AB - In the current issue of Neuron, Bacioglu, Maia, and colleagues show that neurofilament light concentrations in body fluids reflect pathology and symptoms in mouse models of cerebral proteopathies and that these findings translate to human disease (Bacioglu et al., 2016). PMID- 27387644 TI - NMDA Receptors: Power Switches for Oligodendrocytes. AB - The role of NMDA receptors in oligodendrocytes has been controversial. A new paper (Saab et al., 2016) suggests they play a key role in regulating glucose uptake in response to axonal glutamate release, thus controlling metabolic cooperation between oligodendrocytes and axons. PMID- 27387645 TI - Sensing pH with TMCs. AB - Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C. elegans. In this issue of Neuron, Wang et al. (2016) report that C. elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive. PMID- 27387646 TI - Time, Not Size, Matters for Striatal Reward Predictions to Dopamine. AB - Midbrain dopamine neurons encode reward prediction errors. In this issue of Neuron, Takahashi et al. (2016) show that the ventral striatum provides dopamine neurons with prediction information specific to the timing, but not the quantity, of reward, suggesting a surprisingly nuanced neural implementation of reward prediction errors. PMID- 27387647 TI - Taking Psychiatry Research Online. AB - Psychiatry is in need of a major overhaul. In order to improve the precision with which we can treat, classify, and research mental health problems, we need bigger datasets than ever before. Web-based data collection provides a novel solution. PMID- 27387648 TI - Hippocampal Place Cells Couple to Three Different Gamma Oscillations during Place Field Traversal. AB - Three distinct gamma oscillations, generated in different CA1 layers, occur at different phases of concurrent theta oscillation. In parallel, firing of place cells displays phase advancement over successive cycles of theta oscillations while an animal passes through the place field. Is the theta-phase-precessing output of place cells shaped by distinct gamma oscillations along different theta phases during place field traversal? We simultaneously recorded firing of place cells and three layer-specific gamma oscillations using current-source-density analysis of multi-site field potential measurements in mice. We show that spike timing of place cells can tune to all three gamma oscillations, but phase coupling to the mid-frequency gamma oscillation conveyed from the entorhinal cortex was restricted to leaving a place field. A subset of place cells coupled to two different gamma oscillations even during single-place field traversals. Thus, an individual CA1 place cell can combine and relay information from multiple gamma networks while the animal crosses the place field. PMID- 27387650 TI - Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain. AB - Altered microRNA profiles have been implicated in human brain disorders. However, the functional contribution of individual microRNAs to neuronal development and function is largely unknown. Here, we report biological functions for miR-19 in adult neurogenesis. We determined that miR-19 is enriched in neural progenitor cells (NPCs) and downregulated during neuronal development in the adult hippocampus. By manipulating miR-19 in NPCs for gain- and loss-of-function studies, we discovered that miR-19 regulates cell migration by directly targeting Rapgef2. Concordantly, dysregulation of miR-19 in NPCs alters the positioning of newborn neurons in the adult brain. Furthermore, we found abnormal expression of miR-19 in human NPCs generated from schizophrenic patient-derived induced pluripotent stem cells (iPSCs) that have been described as displaying aberrant migration. Our study demonstrates the significance of posttranscriptional gene regulation by miR-19 in preventing the irregular migration of adult-born neurons that may contribute to the etiology of schizophrenia. PMID- 27387651 TI - Cash transfers, maternal depression and emotional well-being: Quasi-experimental evidence from India's Janani Suraksha Yojana programme. AB - Maternal depression is an important public health concern. We investigated whether a national-scale initiative that provides cash transfers to women giving birth in government health facilities, the Janani Suraksha Yojana (JSY), reduced maternal depression in India's largest state, Uttar Pradesh. Using primary data on 1695 women collected in early 2015, our quasi-experimental design exploited the fact that some women did not receive the JSY cash due to administrative problems in its disbursement - reasons that are unlikely to be correlated with determinants of maternal depression. We found that receipt of the cash was associated with an 8.5% reduction in the continuous measure of maternal depression and a 36% reduction in moderate depression. There was no evidence of an association with measures of emotional well-being, namely happiness and worry. The results suggest that the JSY had a clinically meaningful effect in reducing the burden of maternal depression, possibly by lessening the financial strain of delivery care. They contribute to the evidence that financial incentive schemes may have public health benefits beyond improving uptake of targeted health services. PMID- 27387649 TI - Parkinsonism Driven by Antipsychotics Originates from Dopaminergic Control of Striatal Cholinergic Interneurons. AB - Typical antipsychotics can cause disabling side effects. Specifically, antagonism of D2R signaling by the typical antipsychotic haloperidol induces parkinsonism in humans and catalepsy in rodents. Striatal dopamine D2 receptors (D2R) are major regulators of motor activity through their signaling on striatal projection neurons and interneurons. We show that D2R signaling on cholinergic interneurons contributes to an in vitro pause in firing of these otherwise tonically active neurons and to the striatal dopamine/acetylcholine balance. The selective ablation of D2R from cholinergic neurons allows discrimination between the motor reducing and cataleptic effects of antipsychotics. The cataleptic effect of antipsychotics is triggered by blockade of D2R on cholinergic interneurons and the consequent increase of acetylcholine signaling on striatal projection neurons. These studies illuminate the critical role of D2R-mediated signaling in regulating the activity of striatal cholinergic interneurons and the mechanisms of typical antipsychotic side effects. PMID- 27387652 TI - Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer. AB - Gastric cancer, highly dependent on tumor angiogenesis, causes uncontrolled lethality, in part due to chemoresistance. Here, we demonstrate that linifanib (ABT-869), a novel multi-targeted receptor tyrosine kinase inhibitor, markedly augments cytotoxicity of chemotherapies in human gastric cancer. ABT-869 and chemotherapeutic agents exhibited a strong synergy to inhibit the viability of several gastric cancer cell lines, with combination index values ranging from 0.017 to 0.589. Additionally, the combination of ABT-869 and chemotherapeutic agents led to remarkable suppression of vascular endothelial growth factor (VEGF) induced angiogenesis in vitro and in vivo. Importantly, in a preclinical gastric cancer xenograft mouse model, drug co-treatments led to increased mouse survival as well as a synergistic reduction in tumor size and the inhibition of tumor angiogenesis. Mechanistic studies further revealed that all of the co-treatments containing ABT-869 resulted in decreased activation of the VEGF receptor, the epidermal growth factor receptor and the insulin growth factor receptor. Inhibition of these receptor tyrosine kinases consequently attenuated the activation of the downstream AKT/mTOR signaling pathway both in cultured gastric cancer cells and in gastric cancer xenografts. Collectively, our findings suggest that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. PMID- 27387653 TI - Aqueous Phase Synthesis and Enhanced Field Emission Properties of ZnO-Sulfide Heterojunction Nanowires. AB - ZnO-CdS, ZnO-ZnS, and ZnO-Ag2S core-shell heterojunction structures were fabricated using low-temperature, facile and simple aqueous solution approaches. The polycrystalline sulfide shells effectively enhance the field emission (FE) properties of ZnO nanowires arrays (NWAs). This results from the formation of the staggered gap heterointerface (ZnO-sulfide) which could lead to an energy well at the interfaces. Hence, electrons can be collected when an electric field is applied. It is observed that ZnO-ZnS NWAs have the lowest turn-on field (3.0 VMUm(-1)), compared with ZnO-CdS NWAs (6.3 VMUm(-1)) and ZnO-Ag2S NWAs (5.0 VMUm( 1)). This may be associated with the pyramid-like ZnS shell which increases the number of emission nanotips. Moreover, the Fowler-Nordheim (F-N) plot displays a nonlinear relationship in the low and high electric field regions caused by the double well potential effect of the heterojunction structures. PMID- 27387654 TI - Suicide, Self-harm, and Depression After Gastric Bypass Surgery: A Nationwide Cohort Study. AB - OBJECTIVE: The aim of this study was to examine risk of self-harm, hospitalization for depression and death by suicide after gastric bypass surgery (GBP). SUMMARY OF BACKGROUND DATA: Concerns regarding severe adverse psychiatric outcomes after GBP have been raised. METHODS: This nationwide, longitudinal, self matched cohort encompassed 22,539 patients who underwent GBP during 2008 to 2012. They were identified through the Swedish National Patient Register, the Prescribed Drug Register, and the Causes of Death Register. Follow-up time was up to 2 years. Main outcome measures were hazard ratios (HRs) for post-surgery self harm or hospitalization for depression in patients with presurgery self-harm and/or depression compared to patients without this exposure; and standardized mortality ratio (SMR) for suicide post-surgery. RESULTS: A diagnosis of self-harm in the 2 years preceding surgery was associated with an HR of 36.6 (95% confidence interval [CI] 25.5-52.4) for self-harm during the 2 years of follow up, compared to GBP patients who had no self-harm diagnosis before surgery. Patients with a diagnosis of depression preceding GBP surgery had an HR of 52.3 (95% CI 30.6-89.2) for hospitalization owing to depression after GBP, compared to GBP patients without a previous diagnosis of depression. The SMR for suicide after GBP was increased among females (n = 13), 4.50 (95% CI 2.50-7.50). The SMR among males (n = 4), was 1.71 (95% CI 0.54-4.12). CONCLUSIONS: The increased risk of post-surgery self-harm and hospitalization for depression is mainly attributable to patients who have a diagnosis of self-harm or depression before surgery. Raised awareness is needed to identify vulnerable patients with history of self-harm or depression, which may be in need of psychiatric support after GBP. PMID- 27387656 TI - Encapsulation of health-promoting ingredients: applications in foodstuffs. AB - Many nutritional experts and food scientists are interested in developing functional foods containing bioactive agents and many of these health-promoting ingredients may benefit from nano/micro-encapsulation technology. Encapsulation has been proven useful to improve the physical and the chemical stability of bioactive agents, as well as their bioavailability and efficacy, enabling their incorporation into a wide range of formulations aimed to functional food production. There are several reviews concerning nano/micro-encapsulation techniques, but none are focused on the incorporation of the bioactive agents into food matrices. The aim of this paper was to investigate the development of microencapsulated food, taking into account the different bioactive ingredients, the variety of processes, techniques and coating materials that can be used for this purpose. PMID- 27387659 TI - Instability and Spontaneous Reconstruction of Few-Monolayer Thick GaN Graphitic Structures. AB - Two-dimensional (2D) semiconductors are a very hot topic in solid state science and technology. In addition to van der Waals solids that can be easily formed into 2D layers, it was argued that single layers of nominally 3D tetrahedrally bonded semiconductors, such as GaN or ZnO, also become flat in the monolayer limit; the planar structure was also proposed for few-layers of such materials. In this work, using first-principles calculations, we demonstrate that contrary to the existing consensus the graphitic structure of few-layer GaN is unstable and spontaneously reconstructs into a structure that remains hexagonal in plane but with covalent interlayer bonds that form alternating octagonal and square (8|4 Haeckelite) rings with pronounced in-plane anisotropy. Of special interest is the transformation of the band gap from indirect in planar GaN toward direct in the Haeckelite phase, making Haeckelite few-layer GaN an appealing material for flexible nano-optoelectronics. PMID- 27387658 TI - Factors Associated with a Positive Baseline Screening Exam Result in the National Lung Screening Trial. AB - RATIONALE: Lung cancer screening with low-dose computed tomography (LDCT) has been shown to decrease mortality in eligible high-risk patients. However, this mortality benefit comes with a high rate of false-positive findings, which require further evaluation. OBJECTIVES: To identify patient- and center-specific factors associated with having a pulmonary nodule on baseline LDCT, and to develop a prediction rule to help in shared decision making. METHODS: We identified individuals who underwent baseline LDCT screening as part of the National Lung Screening Trial. A positive screen was defined as a nodule 4 mm or greater in largest dimension. Using multiple logistic regression, we identified variables independently associated with having a positive screen. MEASUREMENTS AND MAIN RESULTS: Among the 26,004 patients with complete data who underwent baseline LDCT, 7,123 patients (27%) had a positive screen. In a multivariate analysis, older age (odds ratio [OR] = 1.03 per 1-year increase, 95% confidence interval [CI] = 1.03-1.04), female sex (OR = 1.08, 95% CI = 1.01-1.14), white race (OR = 1.39, 95% CI = 1.25-1.55), heavier smoking history (OR = 1.02 per 5 pack-years smoked over 30, 95% CI = 1.00-1.04), history of chronic obstructive pulmonary disease (OR = 1.08, 95% CI = 1.01-1.17), being married (OR = 1.08, 95% CI = 1.02-1.15), hard rock mining (OR = 1.40, 95% CI = 1.04-1.89), and farm work (OR = 1.13, 95% CI = 1.03-1.23) were independently associated with having a positive screen, whereas having a college degree (OR = 0.94, 95% CI = 0.86-1.00) and abstinence from smoking (OR = 0.98 per year, 95% CI = 0.98-0.99) were associated with not having a positive screen. Patients enrolled at a site in an area highly endemic for histoplasma were 30% more likely to have a positive baseline LDCT screen (OR = 1.30, 95% CI = 1.21-1.40). The area under the receiver operator characteristic curve for the full model was 0.57 (0.56-0.58); including enrollment center as a random effect increased the area under the receiver operator characteristic curve to 0.65. CONCLUSIONS: In the National Lung Screening Trial, both patient- and center-specific factors were associated with having a positive baseline screen. Although the model does not have sufficient accuracy to provide personalized risk estimates to guide shared decision making on an individual basis, it can nonetheless inform screening centers of the likelihood of further follow-up testing for their populations at large when allocating resources. Data collected from centers as broad-based screening is implemented can be used to improve model accuracy further. PMID- 27387660 TI - Syntrophic associations from hypersaline soda lakes converting organic acids and alcohols to methane at extremely haloalkaline conditions. AB - Until now anaerobic oxidation of VFA at high salt-pH has been demonstrated only at sulfate-reducing conditions. Here, we present results of a microbiological investigation of anaerobic conversion of organic acids and alcohols at methanogenic conditions by syntrophic associations enriched from hypersaline soda lakes in Central Asia. Sediment incubation experiments showed active, albeit very slow, methane formation from acetate, propionate, butyrate and C2 ?C4 alcohols at pH 10 and various levels of salinity. Enrichments of syntrophic associations using hydrogenotrophic members of the genus Methanocalculus from soda lakes as partners resulted in several highly enriched cultures converting acetate, propionate, butyrate, benzoate and EtOH to methane. Most syntrophs belonged to Firmicutes, while the propionate-oxidizer formed a novel lineage within the family Syntrophobacteraceae in the Deltaproteobacteria. The acetate-oxidizing syntroph was identified as 'Ca. Syntrophonatronum acetioxidans' previously found to oxidize acetate at sulfate-reducing conditions up to salt-saturating concentrations. Butyrate and a benzoate-degrading syntrophs represent novel genus level lineages in Syntrophomonadales which are proposed as Candidatus taxons 'Syntrophobaca', 'Syntrophocurvum' and 'Syntropholuna'. Overall, despite very slow growth, the results indicated the presence of a functionally competent syntrophic community in hypersaline soda lakes, capable of efficient oxidation of fermentation products to methane at extremely haloalkaline conditions. PMID- 27387657 TI - Finding Our Way in the Dark Proteome. AB - The traditional structure-function paradigm has provided significant insights for well-folded proteins in which structures can be easily and rapidly revealed by X ray crystallography beamlines. However, approximately one-third of the human proteome is comprised of intrinsically disordered proteins and regions (IDPs/IDRs) that do not adopt a dominant well-folded structure, and therefore remain "unseen" by traditional structural biology methods. This Perspective considers the challenges raised by the "Dark Proteome", in which determining the diverse conformational substates of IDPs in their free states, in encounter complexes of bound states, and in complexes retaining significant disorder requires an unprecedented level of integration of multiple and complementary solution-based experiments that are analyzed with state-of-the art molecular simulation, Bayesian probabilistic models, and high-throughput computation. We envision how these diverse experimental and computational tools can work together through formation of a "computational beamline" that will allow key functional features to be identified in IDP structural ensembles. PMID- 27387661 TI - Silent Coronary Artery Disease in Symptomatic Candidates for Carotid Revascularization Intervention. AB - BACKGROUND: Concurrent coronary artery disease (CAD) and carotid artery stenosis (CAS) are frequently detected in clinical practice and have important prognostic implications in symptomatic patients who are considered for revascularization. The aim of this study was to assess the frequency of asymptomatic CAD in stroke patients with CAS and the associated factors. METHODS: Coronary angiography was performed at a single session after cerebral angiography in patients with symptomatic CAS, which was considered a candidate for revascularization. RESULTS: Ninety-six patients were enrolled. We detected significant (defined as a degree of stenosis >=50%) atherosclerotic coronary lesions in 58 patients (60.4%). Of these 58 patients, 32 (55.2%) had one-vessel, 19 (32.7%) 2-vessel, and 7 (12.1%) 3-vessel disease. Potential factors associated with the silent CAD were hypertension (OR 3.86, p = 0.022), a high level (>=140 mg/dl) of non-high-density lipoprotein cholesterol (OR 3.20, p = 0.041), and combined intracranial atherosclerosis steno-occlusion on cerebral angiogram (OR 4.39, p = 0.015). CONCLUSIONS: About 60% of stroke patients with extracranial CAS have an incident CAD. Hypertension, hyperlipidemia, and the atherosclerotic changes of combined extracranial carotid and intracranial arteries may increase the risk of asymptomatic CAD in symptomatic candidates for carotid revascularization intervention. PMID- 27387655 TI - Connexins and their channels in inflammation. AB - Inflammation may be caused by a variety of factors and is a hallmark of a plethora of acute and chronic diseases. The purpose of inflammation is to eliminate the initial cell injury trigger, to clear out dead cells from damaged tissue and to initiate tissue regeneration. Despite the wealth of knowledge regarding the involvement of cellular communication in inflammation, studies on the role of connexin-based channels in this process have only begun to emerge in the last few years. In this paper, a state-of-the-art overview of the effects of inflammation on connexin signaling is provided. Vice versa, the involvement of connexins and their channels in inflammation will be discussed by relying on studies that use a variety of experimental tools, such as genetically modified animals, small interfering RNA and connexin-based channel blockers. A better understanding of the importance of connexin signaling in inflammation may open up towards clinical perspectives. PMID- 27387662 TI - Letter to the editor: Method to evaluate the abilities of scores to predict mortality: rather than receiver operating characteristic curves. PMID- 27387664 TI - Art and Alchemy: The Mystery of Transformation. PMID- 27387663 TI - Triage decisions for ICU admission: Report from the Task Force of the World Federation of Societies of Intensive and Critical Care Medicine. AB - Demand for intensive care unit (ICU) resources often exceeds supply, and shortages of ICU beds and staff are likely to persist. Triage requires careful weighing of the benefits and risks involved in ICU admission while striving to guarantee fair distribution of available resources. We must ensure that the patients who occupy ICU beds are those most likely to benefit from the ICU's specialized technology and professionals. Although prognosticating is not an exact science, preference should be given to patients who are more likely to survive if admitted to the ICU but unlikely to survive or likely to have more significant morbidity if not admitted. To provide general guidance for intensivists in ICU triage decisions, a task force of the World Federation of Societies of Intensive and Critical Care Medicine addressed 4 basic questions regarding this process. The team made recommendations and concluded that triage should be led by intensivists considering input from nurses, emergency medicine professionals, hospitalists, surgeons, and allied professionals. Triage algorithms and protocols can be useful but can never supplant the role of skilled intensivists basing their decisions on input from multidisciplinary teams. Infrastructures need to be organized efficiently both within individual hospitals and at the regional level. When resources are critically limited, patients may be refused ICU admission if others may benefit more on the basis of the principle of distributive justice. PMID- 27387665 TI - Characterization of Vaginal Escherichia coli Isolated from Pregnant Women in Two Different African Sites. AB - The relevance of vaginal colonization of pregnant women by Escherichia coli is poorly understood, despite these strains sharing a similar virulence profile with other extraintestinal pathogenic E. coli producing severe obstetric and neonatal infections. We characterized the epidemiology, antimicrobial susceptibility and virulence profiles of 84 vaginal E. coli isolates from pregnant women from Rabat (Morocco) and Manhica (Mozambique), two very distinct epidemiological settings. Low levels of antimicrobial resistance were observed to all drugs tested, except for trimethoprim-sulfamethoxazole in Manhica, where this drug is extensively used as prophylaxis for opportunistic HIV infections. The most prevalent virulence factors were related to iron acquisition systems. Phylogroup A was the most common in Rabat, while phylogroups E and non-typeable were the most frequent in Manhica. Regardless of the apparently "low virulence" of these isolates, the frequency of infections is higher and the outcomes more devastating in constrained-resources conditions, especially among pregnant women and newborns. PMID- 27387667 TI - Left ventricular pacing vector selection by novel echo-particle imaging velocimetry analysis for optimization of quadripolar cardiac resynchronization device: a case report. AB - BACKGROUND: The availability of pacing configurations offered by quadripolar left ventricular leads could improve patients' response to cardiac resynchronization therapy; however, the selection of an optimal setting remains a challenge. Echo particle imaging velocimetry has shown that regional anomalies of synchrony/synergy of the left ventricle are related to the alteration, reduction, or suppression of the physiological intracavitary pressure gradients. These observations are also supported by several numerical models of the left ventricle that have shown the close relationship between wall motion abnormalities, change of intraventricular flow dynamics, and abnormal distribution of forces operating on the ventricular endocardium. CASE PRESENTATION: A 73-year-old white man in New York Heart Association III functional class with an ejection fraction of 27.5 % did not improve after 1 month of cardiac resynchronization therapy. Five configurations were tested and settings were defined by optimizing intraventricular flow. After 6 months, he became New York Heart Association II class with left ventricular ejection fraction of 53.2 %. CONCLUSIONS: The abnormal dynamic of pressure gradients during the cardiac cycle, through biohumoral endocrine, autocrine, and paracrine transduction, may lead to structural changes of the myocardial walls with subsequent left ventricular remodeling. The echo-particle imaging velocimetry technique may be useful for elucidating the favorable effects of cardiac resynchronization therapy on intraventricular fluid dynamics and it could be used to identify appropriate pacing setting during acute echocardiographic optimization of left pacing vector. PMID- 27387668 TI - Optogenetic Activation of a Lateral Hypothalamic-Ventral Tegmental Drive-Reward Pathway. AB - Electrical stimulation of the lateral hypothalamus can motivate feeding or can serve as a reward in its own right. It remains unclear whether the same or independent but anatomically overlapping circuitries mediate the two effects. Electrical stimulation findings implicate medial forebrain bundle (MFB) fibers of passage in both effects, and optogenetic studies confirm a contribution from fibers originating in the lateral hypothalamic area and projecting to or through the ventral tegmental area. Here we report that optogenetic activation of ventral tegmental fibers from cells of origin in more anterior or posterior portions of the MFB failed to induce either reward or feeding. The feeding and reward induced by optogenetic activation of fibers from the lateral hypothalamic cells of origin were influenced similarly by variations in stimulation pulse width and pulse frequency, consistent with the hypothesis of a common substrate for the two effects. There were, however, several cases where feeding but not self stimulation or self-stimulation but not feeding were induced, consistent with the hypothesis that distinct but anatomically overlapping systems mediate the two effects. Thus while optogenetic stimulation provides a more selective tool for characterizing the mechanisms of stimulation-induced feeding and reward, it does not yet resolve the question of common or independent substrates. PMID- 27387666 TI - Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells. AB - Internal tandem duplication (ITD) mutations in the Fms-related tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML). Due to the development of drug resistance, few FLT3-ITD inhibitors are effective against FLT3-ITD+ AML. In this study, we show that FLT3 ITD activates a novel pathway involving p21Cdkn1a (p21) and pre-B cell leukemia transcription factor 1 (Pbx1) that attenuates FLT3-ITD cell proliferation and is involved in the development of drug resistance. FLT3-ITD up-regulated p21 expression in both mouse bone marrow c-kit+-Sca-1+-Lin- (KSL) cells and Ba/F3 cells. The loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of concomitantly enriching the S+G2/M phase population and significantly increasing the expression of Pbx1, but not Evi-1, in FLT3-ITD+ cells. This enhanced cell proliferation following the loss of p21 was partially abrogated when Pbx1 expression was silenced in FLT3-ITD+ primary bone marrow colony-forming cells and Ba/F3 cells. When FLT3-ITD was antagonized with AC220, a selective inhibitor of FLT3-ITD, p21 expression was decreased coincident with Pbx1 mRNA up-regulation and a rapid decline in the number of viable FLT3-ITD+ Ba/F3 cells; however, the cells eventually became refractory to AC220. Overexpressing p21 in FLT3-ITD+ Ba/F3 cells delayed the emergence of cells that were refractory to AC220, whereas p21 silencing accelerated their development. These data indicate that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression. PMID- 27387669 TI - Human Papillomavirus-Associated Cancers - United States, 2008-2012. AB - Human papillomavirus (HPV) is a known cause of cervical cancers, as well as some vulvar, vaginal, penile, oropharyngeal, anal, and rectal cancers (1,2). Although most HPV infections are asymptomatic and clear spontaneously, persistent infections with one of 13 oncogenic HPV types can progress to precancer or cancer. To assess the incidence of HPV-associated cancers, CDC analyzed 2008-2012 high-quality data from the CDC's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results program. During 2008-2012, an average of 38,793 HPV-associated cancers were diagnosed annually, including 23,000 (59%) among females and 15,793 (41%) among males. By multiplying these counts by the percentages attributable to HPV (3), CDC estimated that approximately 30,700 new cancers were attributable to HPV, including 19,200 among females and 11,600 among males. Cervical precancers can be detected through screening, and treatment can prevent progression to cancer; HPV vaccination can prevent infection with HPV types that cause cancer at cervical and other sites (3). Vaccines are available for HPV types 16 and 18, which cause 63% of all HPV-associated cancers in the United States, and for HPV types 31, 33, 45, 52, and 58, which cause an additional 10% (3). Among the oncogenic HPV types, HPV 16 is the most likely to both persist and to progress to cancer (3). The impact of these primary and secondary prevention interventions can be monitored using surveillance data from population-based cancer registries. PMID- 27387670 TI - Pseudoachalasia presenting 20 years after Nissen fundoplication: a case report. AB - BACKGROUND: Pseudoachalasia is a rare diagnosis manifested by clinical and physiologic symptoms of achalasia, with alternative etiology for outflow obstruction. While malignancy is a frequent cause of pseudoachalasia, prior surgical intervention especially surgery involving the esophagogastric junction, may result in a misdiagnosis of achalasia. CASE PRESENTATION: We present a case of a 70 year-old male with dysphagia and weight loss after undergoing a Billroth I and Nissen fundoplication several decades ago. His preoperative studies suggested achalasia and he was therefore referred for an endoscopic myotomy. However, careful interpretation of all the data and intra-operative findings revealed a classic mechanical and functional obstruction requiring takedown of his prior wrap. CONCLUSIONS: Individualized interpretation of preoperative studies in the setting of prior foregut surgery is critical to appropriate diagnosis and intervention. This case highlights the significance of endoscopic findings and features of high-resolution manometry specific to pseudoachalasia, which contrasts with classical features of achalasia. PMID- 27387671 TI - Photoreceptors mapping from past history till date. AB - The critical source of information in plants is light, which is perceived by receptors present in plants and animals. Receptors present in plant and animal system regulate important processes, and knowing the chromophores and signalling domains for each receptor could pave a way to trace out links between these receptors. The signalling mechanism for each receptor will give insight knowledge. This review has focussed on the photoreceptors from past history till date, that have evolved in the plant as well as in the animal system (to lesser extent). We have also focussed our attention on finding the links between the receptors by showing the commonalities as well as the differences between them, and also tried to trace out the links with the help of chromophores and signalling domain. Several photoreceptors have been traced out, which share similarity in the chromophore as well as in the signalling domain, which indicate towards the evolution of photoreceptors from one another. For instance, cryptochrome has been found to evolve three times from CPD photolyase as well as evolution of different types of phytochrome is a result of duplication and divergence. In addition, similarity between the photoreceptors suggested towards evolution from one another. This review has also discussed possible mechanism for each receptor i.e. how they regulate developmental processes and involve what kinds of regulators and also gives an insight on signalling mechanisms by these receptors. This review could also be a new initiative in the study of UVR8 associated studies. PMID- 27387672 TI - 1,2,4-Triazolo-quinazoline-thiones: Non-conventional synthetic approach, study of solvatochromism and antioxidant assessment. AB - A non-conventional methodology has been utilized for the synthesis of a series of 1,2,4-triazolo-quinazoline-thiones (2a-l). Here the reaction was carried out between 1,2,4-triazolo-quinazolinones (1a-l), in the presence of 1,4-dioxane. The mixture was irradiated under microwave (100W) for 7min to obtain targeted molecules (2a-l). All the synthesized molecules were confirmed by (1)H, (13)C NMR and HRMS. The solvatochromic property (absorption spectra) of compounds (2a-l) in solvents of different polarities was studied. The compounds (2a-l) were further subjected for their in vitro free radical screening using 2,2-diphenyl-1 picrylhydrazyl (DPPH) method and also screened for their in vitro anti-fungal property against Aspergillus flavus (A. flavus) and Aspergillus niger (A. niger). The results from free radical scavenging assay showed promising activity for compounds 2a, e-i, whereas compound 2d showed significant antioxidant activity when compared to ascorbic acid. In vitro anti-fungal study showed that the 1,2,4 triazolo-quinazoline-thiones (2a-l) had significant activity against A. flavus and A. niger compared with widely used antifungal agent Fluconazole. PMID- 27387673 TI - Structural optimization of structured carbon-based energy-storing composite materials used in space vehicles. AB - The hot work environment of electronic components in the instrument cabin of spacecraft was researched, and a new thermal protection structure, namely graphite carbon foam, which is an impregnated phase-transition material, was adopted to implement the thermal control on the electronic components. We used the optimized parameters obtained from ANSYS to conduct 2D optimization, 3-D modeling and simulation, as well as the strength check. Finally, the optimization results were verified by experiments. The results showed that after optimization, the structured carbon-based energy-storing composite material could reduce the mass and realize the thermal control over electronic components. This phase transition composite material still possesses excellent temperature control performance after its repeated melting and solidifying. PMID- 27387674 TI - Pseudomonas aeruginosa identified as a key pathogen in hospitalised children with aspiration pneumonia and a high aspiration risk. AB - AIM: Data on the causative pathogens and optimal empirical therapy of aspiration pneumonia in children are limited. This study sought to describe the bacteriology of aspiration pneumonia in hospitalised children with a high aspiration risk. METHODS: Respiratory tract specimens were prospectively collected using the induced sputum technique from children with a high aspiration risk who were hospitalised for aspiration pneumonia in a tertiary paediatric medical centre from 2009 to 2014. Clinical, microbiological and treatment data were recorded and analysed for each admission. RESULTS: The cohort comprised 50 children with 235 hospital admissions. Of the 183 respiratory tract cultures performed, 110 were positive for bacteria, with 169 isolates, mostly Gram-negative. The most common Gram-negative pathogen was Pseudomonas aeruginosa. If patients had Pseudomonas aeruginosa isolation, the risk of them having the pathogen again was 81%. The multivariate analysis showed that the use of antibiotic prophylaxis and number of hospitalisations were significantly associated with Pseudomonas aeruginosa isolation. CONCLUSION: Gram-negative bacilli, especially Pseudomonas aeruginosa, were the major causative agents of paediatric aspiration pneumonia in our study. Empiric antipseudomonas treatment should be considered, particularly in patients who are receiving antibiotic prophylaxis, have experienced recurrent hospitalisations or with previous respiratory cultures that showed Pseudomonas aeruginosa isolation. PMID- 27387675 TI - Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study. AB - The circadian-related hormones, melatonin and cortisol, have oncostatic and immunosuppressive properties. This study examined the relationship between these two biomarkers and the presence of prostate cancer. We measured their major metabolites in urine collected from 120 newly diagnosed prostate cancer patients and 240 age-matched controls from January 2011 to April 2014. Compared with patients with lower urinary melatonin-sulfate or melatonin-sulfate/cortisol (MT/C) ratio levels, those with above-median levels were significantly less likely to have prostate cancer (adjusted OR (aOR) = 0.59, 95% CI = 0.35-0.99; aOR = 0.46, 95% CI: 0.27-0.77) or advanced stage prostate cancer (aOR = 0.49, 95% CI = 0.26-0.89; aOR = 0.33, 95% CI = 0.17-0.62). The combined effect of both low MT/C ratios and PSA levels exceeding 10 ng/ml was an 8.82-fold greater likelihood of prostate cancer and a 32.06-fold greater likelihood of advanced stage prostate cancer, compared to those with both high MT/C ratios and PSA levels less than 10 ng/ml. In conclusion, patients with high melatonin-sulfate levels or a high MT/C ratio were less likely to have prostate cancer or advanced stage prostate. Besides, a finding of a low MT/C ratio combined with a PSA level exceeding 10 ng/ml showed the greatest potential in detecting prostate cancer and advanced stage prostate cancer. PMID- 27387676 TI - Improvements in the Treatment of Patients Suffering from Bladder-Prostate Rhabdomyosarcoma: A Report from the CWS-2002P Trial. AB - PURPOSE: Modern treatment concepts for bladder/prostate rhabdomyosarcoma (BPRMS) are designed to improve survival, to reduce therapy intensity, and to increase bladder preservation rates. Nevertheless, treatment is not optimal. The purpose of this study was to analyze BPRMS patients treated within the CWS-2002P trial regarding outcome, treatment modalities, complications, and to compare the data with the precursor trial CWS-96. METHODS: Fifty children with localized embryonal BPRMS were analyzed. Eight patients were excluded. Patients received neoadjuvant chemotherapy. At week 9, reassessment using MRI scan was performed. Depending on tumor size, age, and response, local therapy consisting of radiotherapy and/or surgery was initiated. After local therapy, systemic therapy was continued. RESULTS: Patients' median age was 35.6 months. Median follow-up was 59 months. The 5-year OS was 84.5 % and the 5-year ES 79.9 %. Ten patients underwent combined radiochemotherapy and tumor resection (5-year ES: 87.5 %). Six patients were treated solely with radiochemotherapy (5-year ES: 60 %). Twenty-six patients received preoperative chemotherapy followed by tumor resection (ES: 80.8). One patient was treated with chemotherapy only and survived. The bladder preservation rate was 80.9 %. CONCLUSIONS: The outcome within the CWS-2002P trial regarding OS and ES seemed to be better than in the precursor trial CWS-96 due to a reduction of protocol violations, but there was no statistical significant difference possibly due to low numbers. Radiotherapy was used less frequently, and the bladder preservation rate was slightly higher. Novel concepts will be required in the future to improve bladder preservation rates. PMID- 27387677 TI - Tweeting the Meeting: Twitter Use at The American Society of Breast Surgeons Annual Meeting 2013-2016. AB - BACKGROUND: Twitter social media is being used to disseminate medical meeting information. Meeting attendees and other interested parties have the ability to follow and participate in conversations related to meeting content. We analyzed Twitter activity generated from the 2013-2016 American Society of Breast Surgeons Annual Meetings. METHODS: The Symplur Signals database was used to determine number of tweets, tweets per user, and impressions for each meeting. The number of unique physicians, patients/caregivers/advocates, and industry participants was determined. Physician tweeters were cross-referenced with membership and attendance rosters. Tweet transcripts were analyzed for content and tweets were categorized as either scientific, social, administrative, industry promotion, or irrelevant. RESULTS: From 2013 to 2016, the number of tweets increased by 600 %, the number of Twitter users increased by 450 %, and the number of physician tweeters increased by 457 %. The number of impressions (tweets * followers) increased from more than 3.5 million to almost 20.5 million, an increase of 469 %. The majority of tweets were informative (70-80 %); social tweets ranged from 13 to 23 %. A small percentage (3-6 %) of tweets were related to administrative matters. There were very few industry or irrelevant tweets. CONCLUSIONS: Twitter social media use at the American Society of Breast Surgeons annual meeting showed a substantial increase during the time period evaluated. The use of Twitter during professional meetings is a tremendous opportunity to share information. The authors feel that medical conference organizers should encourage Twitter participation and should be educating attendees on the proper use of Twitter. PMID- 27387678 TI - Phase 1b Trial to Evaluate Tissue Response to a Second Dose of Intravesical Recombinant Adenoviral Interferon alpha2b Formulated in Syn3 for Failures of Bacillus Calmette-Guerin (BCG) Therapy in Nonmuscle Invasive Bladder Cancer. AB - BACKGROUND: A phase 1b trial was conducted to evaluate the duration of interferon alpha (IFNalpha) production after intravesical administration of recombinant adenovirus-mediated interferon alpha2b (Ad-IFN) formulated with the excipient Syn3. The primary aim was to determine whether a second instillation 3 days after initial treatment produced prolonged urinary IFN production. METHODS: The study enrolled seven patients who experienced recurrent non-muscle invasive bladder cancer after bacillus Calmette-Guerin therapy. Each treatment consisted of intravesical instillation of SCH721015 (Syn3) and Ad-IFN at a concentration of 3 * 1011 particles/mL to a total volume of 75 mL given on days 1 and 4. The patients were followed for 12 weeks, during which the magnitude and duration of gene transfer were determined by urine INFalpha levels. Drug efficacy was determined by cystoscopy and biopsy, and patients who had no recurrence at 12 weeks were eligible for a second course of treatment. RESULTS: Seven patients were treated with an initial course (instillation on days 1 and 4). Two of the patients had a complete response at 12 weeks and received a second course of treatment. One patient remained without evidence of recurrence after a second course (total 24 weeks). One patient experienced a non-treatment-associated adverse event. Despite a transient rise in IFNalpha levels, sustained production was not demonstrated. CONCLUSION: Previously, Ad-IFNalpha intravesical therapy has shown promising drug efficacy. A prior phase 1 trial with a single instillation compared similarly with the current study, suggesting that a second instillation is not necessary to achieve sufficient urinary IFNalpha levels. PMID- 27387679 TI - Risk Factors for the Development of Desmoid Tumor After Colectomy in Patients with Familial Adenomatous Polyposis: Multicenter Retrospective Cohort Study in Japan. AB - BACKGROUND: Desmoid tumor (DT) is the primary cause of death in patients with familial adenomatous polyposis (FAP) after restorative proctocolectomy. This study aimed to identify risk factors for DT in a Japanese population. METHODS: Clinical data for 319 patients with FAP undergoing first colectomy from 2000 to 2012 were reviewed retrospectively. RESULTS: Two hundred seventy-seven FAP patients were included in this study. Thirty-nine (14.1 %) patients developed DT. Occurrence sites were the intraperitoneal region in 25 (64.1 %) cases, intraperitoneal region and abdominal wall in three (7.7 %), and abdominal wall in nine (23.1 %). The mean period from surgery to DT development was 26.3 months (range 4-120 months). Gender (female vs. male, p = 0.03), age at surgery (>30 vs. <=30 years, p = 0.02), purpose of surgery (prophylactic vs. cancer excision, p = 0.01), and surgical procedure (proctocolectomy [ileoanal anastomosis (IAA), ileoanal canal anastomosis (IACA), total proctocolectomy (TPC)] vs. total colectomy [ileorectal anastomosis, partial colectomy]; p = 0.03) significantly influenced the estimated cumulative risk of developing DT at 5 years after surgery. Conversely, approach (laparoscopic vs. open, p = 0.17) had no significant effect on the increased risk of DT occurrence. In multivariate analysis, female gender, with a hazard ratio of 2.2 (p = 0.02,) and proctocolectomy (IAA, IACA, TPC), with a hazard ratio of 2.2 (p = 0.03), were independent risk factors for DT incidence after colectomy. CONCLUSIONS: Female gender and proctocolectomy (IAA, IACA, TPC) were independent risk factors for developing DT after colectomy in patients with FAP. PMID- 27387680 TI - 8q24 Polymorphisms and Diabetes Mellitus Regulate Apolipoprotein A-IV in Colorectal Carcinogenesis. AB - BACKGROUND: Here, we explored the genetic interactions between diabetes and oncogenic single-nucleotide polymorphisms (SNPs) that determine colorectal cancer (CRC) morbidity. METHODS: 8q24 rs6983267 polymorphism analysis and cDNA microarray were performed in 107 CRCs to identify the genes associated with diabetes and the oncogenic SNP. Then clinical significance of the gene was validated in 132 CRCs. Meta-analysis of microarray data and diabetic comorbidity was performed. RESULTS: Of genes associated with a minor SNP allele at 8q24, diabetes, and MYC overexpression, apolipoprotein A-IV (ApoA-IV) was associated with oncogenesis and poor prognosis in CRC patients. Patients with high ApoA-IV expression showed significantly poorer prognosis by univariate and multivariate analysis. Meta-analysis revealed lipid metabolism was associated with ApoA-IV related oncogenesis in diabetic patients. CONCLUSIONS: Changes in lipid metabolism associated with aberrant expression of ApoA-IV were risks for CRC oncogenesis. PMID- 27387681 TI - Significance of Vascular Resection and Reconstruction in Surgery for Hilar Cholangiocarcinoma: With Special Reference to Hepatic Arterial Resection and Reconstruction. AB - PURPOSE: The aim of this study was to assess the efficacy of combined resection and reconstruction (CRR) of the hepatic artery (HA) in surgery for hilar cholangiocarcinoma (HC). MATERIALS AND METHOD: Among 172 patients who underwent surgical resection for HC, the following three groups were defined according to the type of vascular reconstruction: VR(-) group, in which neither CRR of the portal vein (PV) nor HA was performed (n = 74); VR-PV group, in which only CRR of the PV was required (n = 54); and VR-A group, in which CRR of the HA was performed either with or without CRR of the PV (n = 44). Clinicopathological variables and clinical outcomes were compared among the three groups. RESULTS: Although the VR-A group showed significantly more advanced disease than other groups, the R0 resection rate was comparable among the three groups (VR(-), 74 %; VR-PV, 80 %; VR-A, 80 %). The 5-year disease-specific survival rate was also comparable among the three groups (VR(-), 45.6 %; VR-PV, 51.2 %; VR-A, 22.3 %), but tended to be worse in the VR-A group than in the other groups. A similar trend was observed in morbidity rate. Lymph node metastasis was more frequent in the VR-A group (59 %) than in the other groups (VR(-), 33.8 %; VR-PV, 50 %). In the VR-A group, lymph node metastasis (p = 0.004) and adjuvant chemotherapy (p = 0.006) were determined to represent independent prognostic factors for survival according to multivariate analysis. CONCLUSION: CRR of the HA was considered efficacious in selected patients; however, long-term outcomes of the VR-A group seem unsatisfactory. Treatments additional to surgery may be necessary in cases requiring CRR of the HA. PMID- 27387682 TI - Controversial database of medical records is scrapped over security concerns. PMID- 27387684 TI - [Not Available]. PMID- 27387685 TI - Fever Therapy With Intravenously Applied Mistletoe Extracts for Cancer Patients: A Retrospective Study. AB - PURPOSE: So-called spontaneous remissions in cancer often seem to occur after febrile events. Mistletoe preparations (MPs) are used off-label intravenously to induce fever within concepts of integrative oncology. We wanted to investigate the frequency of febrile reactions and safety related to intravenously applied MPs (IAMPs). METHODS: This was a retrospective analysis of data from consecutive cancer patients who were treated in 2 anthroposophic hospitals with IAMPs. The main outcome parameter was the rate of core temperature increase to >=38.5 degrees C within 24 hours after IAMPs. Secondary outcome parameters were Common Toxicity Criteria for Adverse Events (CTCAE; version 4.0). RESULTS: 59 patients, with in total 567 IAMPs, were analyzed; 45 patients (76%, 95% CI = 65%-87%) had an increase of core temperature to >=38.5 degrees C after at least 1 treatment. Mean increase in temperature was 1.5 degrees C +/- 0.8 degrees C. Adverse events were mostly fever-related symptoms (headache, joint pain, shivering). Grade 1 allergic reactions were documented in 0.6% of treatments. CTCAEs grade 3 to 5 did not occur; 38/59 patients had advanced and/or metastatic disease. CONCLUSION: IAMPs resulted in febrile reactions to >38.5 degrees C in the majority of patients and can be considered as safe. Adverse events were mostly related to fever and were not severe. PMID- 27387683 TI - Associations between Nine Polymorphisms in EXO1 and Cancer Susceptibility: A Systematic Review and Meta-Analysis of 39 Case-control Studies. AB - An increasing number of studies have highlighted the potential link between EXO1 polymorphisms and cancer risk, although no consensus has yet been obtained. Thus, we aimed to obtain a thorough and current assessment of EXO1 polymorphisms and cancer susceptibility by performing a meta-analysis. A comprehensive literature retrieval was performed on PubMed, EMbase, Web of Science and Wanfang databases. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the results. Finally, 39 case-control studies of the nine EXO1 polymorphisms that involved 21,651 cases and 21,348 controls met our inclusion criteria. The pooled analysis indicated that the rs1047840 polymorphism conferred a significantly increased susceptibility to cancer in an allelic model. Similarly, the rs3754093, rs1776177, rs9350, rs10802996, rs1635498, rs1776148 and rs851797 polymorphisms were also associated with an increased susceptibility to cancer in an allelic model, respectively, while no significant association was identified for rs1635517 polymorphism. For the rs1047840 polymorphism, in an ethnicity subgroup analysis, a significantly increased susceptibility to cancer for Asians was identified in all the genetic models, and for Caucasians in an allelic model. Our findings provide the evidence that the rs1047840, rs9350, rs10802996, rs1635498, rs1776148, rs1776177, rs3754093 and rs851797 polymorphisms may act as risk factors for cancer. PMID- 27387686 TI - Pregnancy outcomes in women with childhood-onset and adult-onset systemic lupus erythematosus: a comparative study. AB - To compare the maternal and fetal outcomes between childhood-onset and adult onset systemic lupus erythematosus (SLE), we reviewed the medical records of SLE pregnant women treated from January 2005 to August 2013. For comparison, patients were allocated to one of the two groups, those pregnant patients with SLE onset before 18 years of age (childhood-onset) and >=18 years (adult-onset). The patients were evaluated at least once in each trimester and postpartum. Relevant maternal and fetal outcomes were extracted, such as lupus flare, preeclampsia/eclampsia, rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. We studied 186 pregnancies (in 180 women), 58 of them had childhood-onset SLE, and the remaining 128 had adult-onset SLE. The rate of maternal and fetal complications was similar in both groups. Multivariate analysis showed that active SLE before pregnancy, primigravida, renal flare, preeclampsia, lupus flare, anticardiolipin antibodies, and low serum complement were associated with an increased risk of poor maternal and fetal outcomes. The diagnosis of childhood-onset had no impact on maternal fetal outcome. The maternal and fetal outcome in women with childhood-onset SLE is similar to that reported in women with adult-onset SLE. Pregnancy in women with childhood-onset SLE should not be contraindicated if the disease is well controlled. PMID- 27387687 TI - Febrile attacks triggered by milk allergy in an infant with mevalonate kinase deficiency. PMID- 27387689 TI - Paired Editorial: How should residual or recurrent diabetes after bariatric surgery be managed? PMID- 27387688 TI - Prospective evaluation of routine early computed tomography scanner in laparoscopic sleeve gastrectomy. AB - BACKGROUND: Prompt management of laparoscopic sleeve gastrectomy (LSG) complications is essential in avoiding prolonged hospital stay and associated mortality. The value of routine computed tomography (CT) scan examination in early diagnosis of postoperative complications after LSG has not been studied. OBJECTIVES: To prospectively assess the impact of postoperative day (POD) 2 CT scan after LSG. SETTING: Department of Minimally Invasive Digestive Surgery, Antoine-Beclere Hospital, AP-HP, Paris-Saclay University, France. METHODS: Data were prospectively gathered for 1000 patients undergoing single-incision LSG and POD 2 CT scan. Complications were identified and treatment modalities decided according to the severity of complications. Sensitivity, specificity, and positive and negative predictive values were calculated for the diagnosis of surgical complications on POD 2 CT scan. RESULTS: Mean age was 40.1 years and median BMI 42.6 kg/m2. Early postoperative surgical complications occurred in 66 patients (6.6%). Intraabdominal bleeding/hematoma occurred in 38 patients, with 3 requiring emergent reoperation on POD 1. POD 2 CT scan detected this complication in 32 patients (sensitivity: 91.4%). Twenty-four (63.1%) patients were treated with relaparoscopy and drainage while 14 (36.9%) received conservative management. Postoperative transfusion was required in 7 patients. Twenty-eight patients suffered a gastric staple line leak, 13 (sensitivity: 46.4%) detected on POD 2 CT scan. Three patients (10.7%) received pure surgical treatment, 16 (57.1%) combined relaparoscopy and endoscopic treatment, and 9 (32.2%) had pure endoscopic treatment. CONCLUSION: POD 2 abdominal CT scan is an efficient diagnostic tool for detecting active bleeding/hematoma, but shows less impressive results with gastric staple line leak detection. A combination of clinical surveillance and early imaging allowed prompt management of complicated cases, avoiding further morbidity. PMID- 27387690 TI - Leukocytes in obesity and after bariatric surgery (Comment on: The effect of different bariatric surgery type on the leukocyte formula). PMID- 27387691 TI - Differential response of plasma plasminogen activator inhibitor 1 after weight loss surgery in patients with or without type 2 diabetes. AB - BACKGROUND: Obesity and type 2 diabetes (T2D) are associated with a suppression of fibrinolysis and an increased risk of intravascular thrombi because of elevated plasma plasminogen activator inhibitor 1 (PAI-1). OBJECTIVES: The aim was to investigate PAI-1 levels in obese patients in the early phase after bariatric surgery, before any weight loss, and in the late phase, to identify the impact of reduced adipose mass versus weight loss independent effects on PAI-1 levels. We also studied the impact of T2D on the rate of PAI-1 reduction. SETTINGS: Twelve obese patients with and without T2D (n = 6) who were scheduled for surgery at a designated Center of Excellence. METHODS: Plasma PAI-1 antigen was measured by enzyme-linked immunosorbent assay (ELISA) preoperatively and at 4 and 42 days after gastric bypass surgery. RESULTS: In the early phase, plasma PAI 1 was significantly decreased by 53% (P = .023). This difference did not remain significant in the late phase. However, PAI-1 levels in T2D and non-T2D patients were significantly different (P = .005). In non-T2D patients, plasma PAI-1 levels decreased significantly in both early and late phases (P = .038). Interestingly, in the T2D group, the PAI-1 levels tended to increase in the late phase and differed significantly from the non-T2D group. CONCLUSION: We report decreased PAI-1 levels in the immediate postoperative period after gastric bypass, indicating that a mechanism not related to the fat mass regulates the PAI-1 levels. Additionally, there may be a difference in PAI-1 levels between T2D and non-T2D patients 42 days postoperatively. Further studies are required to verify this difference and to elucidate the specific mechanisms responsible for PAI-1 synthesis. PMID- 27387692 TI - Long-term effects of laparoscopic Roux-en-Y gastric bypass on metabolic syndrome in patients with morbid obesity. AB - BACKGROUND: Diseases associated with obesity such as type 2 diabetes (T2D), hypertension, and dyslipidemia are common and together are defined as metabolic syndrome (MetS). The aim of this study was to evaluate long-term effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) in morbidly obese patients with MetS. METHODS: This was a retrospective study of data from a prospective database in a single center from 2005 to 2013 including 3795 LRYGB operated obese patients. Metabolic syndrome was defined according to the International Diabetes Federation Consensus Definition of Metabolic Syndrome from 2006. RESULTS: In the study population, 79% of the patients were women, the preoperative median age was 42.4 years, and median body mass index (BMI, kg/m2) was 40.9. MetS was diagnosed in 60% of the patients (2275/3795), with increased frequency in men and in those with higher age, higher BMI, and greater waist circumference; 27.5% of patients had impaired glucose metabolism, 40% hypertension, and 30% dyslipidemia. Postoperative follow-up rate>5 years was 71% (595/839). We found that 86.2% had resolution of MetS. After 5-9 years, complete remission of T2D was achieved in 78%, hypertension in 51%, and dyslipidemia in 89%. Mean excess BMI loss was significantly lower for patients with MetS (73.1%) compared with patients without MetS (75.6%) (P<.01). Early complications (leakage or hemorrhage) occurred in 1.2% (48/3975) and internal hernia in 7.8% (310/3975). Presence of MetS did not increase complication rates. CONCLUSION: LRYGB in obese patients is associated with a significant and sustained reduction in excessive weight. In the present study, 86.2% of patients with MetS achieved complete remission and complication rates were low. Early bariatric surgery should be considered in patients with obesity and concurrent MetS. PMID- 27387693 TI - Paired editorial: open total gastrectomy for chronic fistula after sleeve. PMID- 27387695 TI - Open total gastrectomy with Roux-en-Y reconstruction for a chronic fistula after sleeve gastrectomy. AB - BACKGROUND: Surgery appears to be the best treatment option for a chronic fistula after laparoscopic sleeve gastrectomy (LSG). Conservative procedures (conversion into a Roux-en-Y gastric bypass, Roux-limb placement) have proven their feasibility and efficacy, but an open total gastrectomy (TG) is sometimes required in challenging situations. OBJECTIVES: To assess outcomes from 12 consecutive patients who underwent surgery for a post-sleeve gastrectomy chronic fistula (PSGCF) between January 2004 and February 2012. SETTING: University public hospital, France. METHODS: Patients with a PSGCF who underwent surgery were included in this retrospective study. Mortality, morbidity (i.e., Clavien Dindo score), weight loss, and nutritional status were assessed. RESULTS: Twelve of 57 patients (21%) with a post-LSG leak developed a PSGCF. There were 3 men (25%). Mean age was 39+/-9 years and mean preoperative body mass index was 35+/-5 kg/m2. All 12 patients underwent an open total gastrectomy with an esojejunostomy (TG). Conservative procedures were considered but not possible. The mean follow up period was 38+/-11 months. The mean delay between LSG and TG was 12+/-6 months. Intraoperative discovery of multiple (>2) gastric fistulas was reported in 9 patients (75%). There were no deaths, but morbidity rate was 50%. Early postoperative fistula occurred in 3 patients (anastomosis n = 1, duodenal stump n = 2). None of these patients required further surgery. The median healing time of the fistula was 37 days (range 24-53). Promising results from weight loss and nutritional status were found at the end of the follow-up. CONCLUSION: A salvage open TG is a well-tolerated and reproducible salvage procedure for cases of a PSGCF, when conservative procedures are not possible. PMID- 27387694 TI - Does sleeve gastrectomy improve the gait parameters of obese patients? AB - BACKGROUND: Few studies have evaluated the effect of bariatric surgery on gait parameters, which constitute an important aspect of quality of life. OBJECTIVE: Evaluate the effects of sleeve gastrectomy (SG) on kinematic gait parameters 6 months after surgery. SETTING: University Hospital, France, public practice. METHODS: This prospective, nonrandomized study was conducted in patients undergoing SG between January 2013 and December 2013. The primary endpoint was the difference in functional parameters of the patient's 6-minute walk test (6 MWT) before and 6 months after SG. Secondary outcomes were surgical data, weight loss, and quality of life score. RESULTS: Fifty-six patients were included. Mean preoperative body mass index was 46.3+/-7.1 kg/m2 (35.2-71.0). On the preoperative 6 MWT, the mean distance traveled was 467 m (267-606) at an average speed of 4.6 km/hr (2.67-6.06). Three patients were unable to complete the 6 MWT. At 6 months postoperatively, mean body mass index was 34.4+/-6.0 kg/m2 (24.8 53.8). On the 6-month postoperative 6 MWT, the mean distance traveled was 515 m (280-652) at an average speed of 5 km/hr (2.82-6.50; P<.01). All patients completed the test. A decrease in muscle and joint pain and an increased range of motion of the joints were observed (P<.01). All domains of the Short Form 36 questionnaire were significantly improved (P< .01). CONCLUSION: SG significantly improves walking as well as range of motion of the joints. It also allows reduction of pain, facilitating the mobilization of obese patients that may be responsible for more marked weight loss after bariatric surgery. Quality of life improves and weight loss occurs after the SG. PMID- 27387696 TI - Improved glucose metabolism after gastric bypass: evolution of the paradigm. AB - BACKGROUND: Glucose metabolism is improved in patients with type 2 diabetes after Roux-en-Y gastric bypass (RYGB). OBJECTIVES: To quantify the relative contribution of calorie restriction, rerouting of nutrients, and adipose tissue reduction. SETTING: University Hospital. METHODS: Fifteen diabetic patients, (47+/-9 yr, body mass index 41.3+/-4.2 kg/m2) were randomized to a 2-week very low-calorie diet (VLCD) regimen or normal diet before RYGB. A euglycemic hyperinsulinemic clamp, indirect calorimetry, and a standard meal test were performed prediet, postdiet (preoperatively), and 2 weeks and 12 months postoperatively. The primary outcome was whole-body insulin sensitivity (M) measured with the clamp 2 weeks postoperatively. RESULTS: In the VLCD group, after 2 weeks of calorie restriction, M improved (2.9+/-1.3 to 4.2+/-1.1 mg/kg/min, P = .005) with no further change at 2 weeks postoperatively. In the normal diet group 2 weeks postoperatively, M was similar to the VLCD group (4.7+/ 1.7 versus 4.2+/-1.1, P = .61). One year postoperatively, M improved further in both groups. The improvement in insulin-stimulated glucose uptake after VLCD and RYGB was entirely accounted for by nonoxidative glucose disposal (NOGD), whereas weight loss at 1 year postoperatively was associated with an increase in NOGD and glucose oxidation. Postprandial glucose improved after VLCD (P<.05) and even more 2 weeks after RYGB (P<.05) with no further change after 1 year. CONCLUSION: Improved whole-body insulin sensitivity and postprandial glucose response occur early after RYGB. Low calorie intake and rerouting of nutrients contribute through distinct mechanisms. Weight loss contributes by increasing whole-body insulin sensitivity, including glucose oxidation and NOGD. These data suggest that the combination of different mechanisms is what makes RYGB an effective intervention for type 2 diabetes. PMID- 27387697 TI - Gastric bypass reversal: a 7-year experience. AB - BACKGROUND: After gastric bypass, some patients develop conditions that ultimately require reversal of the bypass. There are currently few publications on the topic to guide clinicians. OBJECTIVES: To describe the indications, techniques, and outcomes for gastric bypass reversal. SETTING: Two academic medical centers. METHODS: We conducted a retrospective chart review of all patients who underwent gastric bypass reversal at our institutions between 2008 and 2015. Information regarding the original operation, the indications for reversal, procedures performed, and the postoperative outcomes were collected and analyzed. RESULTS: Nineteen patients underwent gastric bypass reversal. All but 4 reversal operations were performed laparoscopically. The indications for reversal were malnutrition or excessive weight loss (6 patients); chronic nausea, vomiting, and abdominal pain (5); neuroglycopenia (4); massive small bowel loss due to internal hernia (3); and need for surveillance gastric endoscopy (1). In the perioperative period, 4 patients had a complication that required intervention. Five patients required additional delayed procedures. One patient was lost to follow-up. The remaining patients' mean follow-up was 22+/-18 months. Symptoms that prompted reversal of the gastric bypass resolved in the majority of patients. However, 1 patient's hypoglycemia did not resolve and 2 continued to have diarrhea. Six patients were weaned off of total parenteral nutrition. CONCLUSIONS: Laparoscopic gastric bypass reversal is feasible and well tolerated. The procedure can be employed to treat a variety of conditions that may occur after gastric bypass and the majority of patients benefit, with resolution of symptoms. In a carefully selected patient population, gastric bypass reversal should be considered if conservative approaches to adverse conditions fail. PMID- 27387698 TI - The impact of history of exposure to abuse on outcomes after bariatric surgery: data from the Ontario Bariatric Registry. AB - BACKGROUND: Studies worldwide have reported an increased prevalence of abuse histories among bariatric surgery candidates. The impact of abuse history on weight loss after surgery has not been examined in Canada. OBJECTIVES: Determine the prevalence of abuse and its impact on postoperative outcomes in Ontario, Canada. SETTING: Data from the Ontario Bariatric Registry. METHODS: A retrospective cohort study of laparoscopic gastric bypass and sleeve gastrectomy surgeries from 2010 to 2014, for which any follow-up data were available (N = 6016). Weight loss outcomes at 3 months (n = 5147), 6 months (n = 4749), and 1 year (n = 4024) were compared between those with and without a self-reported history of any of emotional, physical or sexual abuse and those with and without a history of sexual abuse specifically. Mixed repeated measures models were adjusted for age, sex, type of surgery, and baseline body mass index. One-year postoperative occurrence of revisions or repairs, hospitalization, and death were also examined. RESULTS: The prevalence of documented abuse was 21.5%. Emotional abuse was most common (13.1%), followed by sexual abuse (10.6%), then physical abuse (8.9%). There was no significant association between presence of abuse history and weight loss at any time point in repeated measures analyses. CONCLUSION: Abuse histories are common in bariatric surgery candidates in Ontario, but at a lower prevalence than what has been reported elsewhere. History of abuse does not appear to affect weight loss out to 1 year postoperatively and may alert providers to offer additional support perioperatively and postoperatively, particularly in the setting of psychiatric co-morbidity. PMID- 27387699 TI - Effect of Roux-en-Y gastric bypass on the remission of type 2 diabetes: a 3-year study in Chinese patients with a BMI <30 kg/m2. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment for patients with type 2 diabetes (T2D) and morbid obesity. However, T2D remission after surgery has not been adequately studied in Chinese patients with a body mass index (BMI)<30 kg/m2. OBJECTIVES: The objective of this study was to evaluate the 3-year effect of RYGB among patients with T2D with a BMI<30 kg/m2 and elucidate the predictors of T2D remission. SETTING: Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. METHODS: Sixty-six Chinese patients with T2D and a BMI 25-30 kg/m2 were retrospectively examined for metabolic outcomes 3 years after RYGB. Remission was defined as glycated hemoglobin (HbA1C)<6.5% and no medications. Binary logistic regression analysis was used to identify preoperative parameters independently predictive of diabetes remission at 1 and 3 years postoperatively [variables: sex, age, BMI, T2D duration, plasma glucose 2 hours after meal, HbA1C, fasting C-peptide, visceral fat area, free triiodothyronine, and thyroid stimulating hormone. There was no significant difference in fasting insulin or glucose between the remission and no remission groups. RESULTS: Patients were a mean 50.4+/-11.4 years of age at baseline, and 57.6% were female. Mean T2D duration was 8.9+/-5.2 years, baseline HbA1C level was 8.3+/-1.9%, and baseline BMI was 28.2+/-1.2 kg/m2 (range: 25.5-30.0). BMI was 22.5+/-1.8 kg/m2 (range: 19.1-28.0) at 1 year and 23.0+/-1.76 kg/m2 (range: 19.7-28.0) at 3 years. Remission was achieved in 49 patients (74.2%) at 1 year and 38 patients (57.6%) at 3 years. There was a significant reduction in medication for diabetes, hypertension, and hyperlipidemia (P<.01). Compared with patients in the no remission group, patients in the remission group had higher fasting C-peptide levels (P<.01) and free triiodothyronine levels (P = .01) at 1 year. Multiple logistic regression analysis confirmed that fasting C-peptide (odds ratio = 3.795, P = .007) and free triiodothyronine (odds ratio = 4.661, P = .019) levels were predictors of T2D remission at 1 year. No significant difference was found between the 2 groups at 3 years. CONCLUSIONS: RYGB resulted in significant clinical and biochemical improvements in Chinese patients with BMI 25-30 kg/m2 and T2D. Appropriate patient selection (better beta-cell function) may produce better outcomes. PMID- 27387701 TI - Erratum: Fluorescence Time-lapse Imaging of the Complete S. venezuelae Life Cycle Using a Microfluidic Device. AB - A correction was made to: Fluorescence Time-lapse Imaging of the Complete S. venezuelae Life Cycle Using a Microfluidic Device The author's name was updated from: Mark Buttner to: Mark J. Buttner. PMID- 27387700 TI - Fat-free mass is not lower 24 months postbariatric surgery than nonoperated matched controls. AB - OBJECTIVE: Concerns about an excessive loss of fat-free mass (FFM) after bariatric surgery prompted this comparison of operated versus matched nonoperated controls regarding FFM. SETTING: University Hospital and University Research Unit in an urban medical center. METHODS: Body composition with bioelectric impedance (Tanita 310, Tanita Corp, Arlington Heights, IL) was measured approximately 2 years after bariatric surgery in weight stable patients and nonoperated weight stable controls matched for body mass index (BMI), gender, and age. t tests provided comparisons. Analysis of variance was used to compare FFM changes for 4 procedures. Levene's test evaluated variance. RESULTS: Patients (n = 252; 24.7+/ 15 mo after surgery) and nonoperated controls (n = 252) were matched for gender (71.8% female), age (44.5+/-11.0 yr), and BMI (32.8+/-7.0 kg/m2). Patients had different surgical procedures: 107 gastric bypasses (RYGBs), 62 biliopancreatic diversions with duodenal switch (BPD/DSs), 40 adjustable gastric bands (AGBs), and 43 sleeve gastrectomies (LSGs). FFM percentage was significantly higher in the operated patients than controls, 66% versus 62%, P<.0001. For 3 procedures, the FFM was significantly higher; however, AGBs changed only 7.3 BMI units and FFM was not significantly different from their matched controls, 59.8% versus 58.2%. Across surgical groups, FFM percentage differed, P<.0001 (RYGB 66.5+/ 9.2%, BPD/DS 74.0+/-9.3%, AGB 59.8+/-7.0%, LSG 59.6+/-9.3%). Variance was not different (P = .17). CONCLUSION: Weight-reduced bariatric surgery patients have greater FFM compared with nonoperated matched controls. These findings support surgically assisted weight loss as a physiologic process and in general patients do not suffer from excessive FFM depletion after bariatric procedures. PMID- 27387702 TI - Quantifying three-dimensional optic axis using polarization-sensitive optical coherence tomography. AB - The optic axis of birefringent samples indicates the direction of optical anisotropy, which should be described in three-dimensional (3-D) space. We present a method to quantify the complete 3-D optic axis orientation calculated from in-plane optic axis measurements from a polarization-sensitive optical coherence tomography system. The in-plane axis orientations with different illumination angles allow the calculation of the necessary polar angle. The method then provides the information to produce the actual birefringence. The method and results from a biological sample are presented. PMID- 27387703 TI - Light distortion and spherical aberration for the accommodating and nonaccommodating eye. AB - To evaluate how different amounts of induced spherical aberration (SA) affect the light distortion (LD) phenomena, tests were performed using an experimental device to measure the distortion (haloes, glare, and so on) of a point source. To simulate the effect of SA, eight different phase plates between +0.300 and -0.300 MUm of SA for a 5-mm aperture were used in a random and double-masked experimental design. Measurements were performed at a distance of 2 m in a darkened room in 10 eyes of five subjects with a mean age of 26.4+/-6.1 years and a mean refractive error of -0.50+/-0.70 D. Data were obtained with natural pupil and after pupil dilatation. The measurements with this experimental system showed a significant increase in all distortion parameters with cycloplegia for the phase plates with the higher positive SA (+0.300 and +0.150 MUm). The disturbance index increased from 14.86+/-6.12% to 57.98+/-36.20% (p<0.05) with the +0.300 MUm plate. The same effect was observed through at a much lower rate when the eye could accommodate. Plates inducing negative SA did not change the LD compared to the control condition without induction of SA or even decreased the effect of distortion. Pupillary dilation and cyclopegia led to a significant increase in the size of the LD when increasing values of SA were induced. Accommodation and pupillary constriction are capable of compensating the degradation of the optical quality induced. PMID- 27387704 TI - Charles Girard: Relationships and Representation in Nineteenth Century Systematics. AB - Early nineteenth century systematists sought to describe what they called the Natural System or the Natural Classification. In the nineteenth century, there was no agreement about the basis of observed patterns of similarity between organisms. What did these systematists think they were doing, when they named taxa, proposed relationships between taxa, and arranged taxa into representational schemes? In this paper I explicate Charles Frederic Girard's (1822-1895) theory and method of systematics. A student of Louis Agassiz, and subsequently (1850-1858) a collaborator with Spencer Baird, Girard claimed that natural classificatory methods do not presuppose either a special creationist or an evolutionary theory of the natural world. The natural system, in Girard's view, comprises three distinct ways in which organisms can be related to each other. Girard analyzed these relationships, and justified his classificatory methodology, by appeal to his embryological and physiological work. Girard offers an explicit theoretical answer to the question, what characters are evidence for natural classificatory hypotheses? I show that the challenge of simultaneously depicting the three distinct types of relationship led Girard to add a third dimension to his classificatory diagrams. PMID- 27387705 TI - The role of hypnotherapy in evidence-based clinical practice. AB - The purpose of this review was to discuss the place of hypnotherapy in a modern medical world dominated by so-called evidence-based clinical practice. Hypnosis is an easily learned technique that is a valuable adjuvant to many medical, dental and psychological interventions. PMID- 27387706 TI - Firefighter willingness to participate in a stem cell clinical trial for burns: A mixed methods study. AB - : Adult stem cells represent a potentially renewable and autologous source of cells to regenerate skin and improve wound healing. Firefighters are at risk of sustaining a burn and potentially benefiting from a split thickness skin graft (STSG). This mixed methods study examined firefighter willingness to participate in a future stem cell clinical trial, outcome priorities and factors associated with this decision. METHODS: A sequential explanatory mixed methods design was used. The quantitative phase (online questionnaire) was followed by the qualitative phase (semi-structured interviews). A sample of 149 firefighters completed the online survey, and a purposeful sample of 15 firefighters was interviewed. RESULTS: A majority (74%) reported they would participate in a future stem cell clinical trial if they experienced burn benefiting from STSG. Hypothetical concerns related to receiving a STSG were pain, itch, scarring/redness and skin durability. Participants indicated willingness to undergo stem cell therapy if the risk of no improvement was 43% or less. Risk tolerance was predicted by perceived social support and having children. Interviews revealed four main themes: a desire to help others, improving clinical outcomes, trusting relationships, and a belief in scientific investigation. Many participants admitted lacking sufficient knowledge to make an informed decision regarding stem cell therapies. CONCLUSIONS: Firefighters indicated they were largely willing to participate in a stem cell clinical trial but also indicated a lack of knowledge upon which to make a decision. Public education of the role of stem cells in STSG will be increasingly important as clinical trials are developed. PMID- 27387707 TI - Total synthesis of atropurpuran. AB - Due to their architectural intricacy and biological significance, the synthesis of polycyclic diterpenes and their biogenetically related alkaloids have been the subject of considerable interest over the last few decades, with progress including the impressive synthesis of several elusive targets. Despite tremendous efforts, conquering the unique structural types of this large natural product family remains a long-term challenge. The arcutane diterpenes and related alkaloids, bearing a congested tetracyclo[5.3.3.0(4,9).0(4,12)]tridecane unit, are included in these unsolved enigmas. Here we report a concise approach to the construction of the core structure of these molecules and the first total synthesis of (+/-)-atropurpuran. Pivotal features of the synthesis include an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, sequential aldol and ketyl-olefin cyclizations to assemble the highly caged framework, and a chemoselective and stereoselective reduction to install the requisite allylic hydroxyl group in the target molecule. PMID- 27387708 TI - A comparison of acute vascular damage caused by ADAPT versus a stent retriever device after thrombectomy in acute ischemic stroke: a histological and ultrastructural study in an animal model. AB - BACKGROUND: It has been amply demonstrated that endovascular procedures can be successful treatment for stroke, both in terms of revascularization and clinical outcome. There is not, however, a published comparison of any histological or ultrastructural damage to the vessels that may be caused by a direct aspiration first pass technique (ADAPT) or stent retrievers (SR) used in these procedures. This study analyses and compares acute damage to the arterial wall caused by ADAPT or SR. MATERIAL AND METHODS: Damage to the walls of swine extracranial arteries was evaluated after ADAPT with the Penumbra system or thrombectomy with an SR (Solitaire 6*30). The procedures were performed after injecting thrombi into the selected arteries (arteries with diameters similar to those of the human internal carotid artery and first segment of the middle cerebral artery). After the procedures, the animal was euthanized and 12 arterial samples were obtained for analysis by optical and electronic microscopy. RESULTS: Tissue samples from the vessels treated with SR showed almost complete loss of endothelium, thickening of the internal elastic lamina, and degeneration of the elastic fibers of the bordering lamina media and adventitia. In contrast, tissue samples of the vessels treated with ADAPT had a clear integral internal elastic lamina and uninterrupted endothelial lining, although cell alignment was altered and there were surface lacerations due to manipulation of the samples. CONCLUSIONS: Both techniques caused acute damage to the vessel walls, however, thrombectomy with SR appeared to be more harmful to all layers of the arterial wall, particularly the endothelium. PMID- 27387709 TI - Combined endovascular coiling and intra-aneurysmal allogeneic mesenchymal stromal cell therapy for intracranial aneurysms in a rabbit model: a proof-of-concept study. AB - OBJECTIVE: To assess the feasibility and efficacy of clinically translatable adjuvant mesenchymal stem/stromal cells (MSCs) therapy in improving the healing of coiled aneurysms in a rabbit elastase aneurysm model. METHODS: Bone marrow derived MSC populations were isolated from three rabbit donors in a serum-free environment and independently characterized to confirm their identity. Elastase induced carotid aneurysms were created in nine New Zealand white rabbits. Each animal received one of the following treatments based on previous randomization: (1) coiling alone (control group); (2) coiling with an intra-aneurysmal injection of saline (vehicle group); and (3) coiling with an intra-aneurysmal injection of 5 million allogeneic MSCs (treatment group). The animals were followed for 4 weeks post-treatment, at the end of which blinded analyses of angiograms and histology were performed. RESULTS: Histological results in the treatment group showed improvements over the control and vehicle groups, although the improvement over the vehicle group was not significant. Intra-aneurysmal cell therapy with 5 million allogeneic MSCs did not result in any major adverse events. Angiographic results did not show any significant difference among groups. CONCLUSIONS: This proof-of-concept study shows that adjuvant MSC therapy for intracranial aneurysms is feasible and may enhance histological improvement of coiled aneurysms at 4 weeks post-treatment. PMID- 27387710 TI - Flow changes in the posterior communicating artery related to flow-diverter stents in carotid siphon aneurysms. AB - BACKGROUND: Flow-diverter stent (FDS) placement for treatment of intracranial aneurysms can cause flow changes in the covered branches. OBJECTIVE: To assess the impact of the treatment of carotid siphon aneurysms with FDS on the posterior communicating artery (PComA) flow. MATERIALS AND METHODS: Between February 2011 and January 2015, 125 carotid siphon aneurysms were treated with FDS. We retrospectively analyzed all cases with PComA ostial coverage. The circle of Willis anatomy was also studied as the flow changes in PComA postoperatively and during angiographic follow-up. Data from neurological examination were also collected. RESULTS: Eighteen aneurysms of the carotid siphon in 17 patients were treated with FDS covering the ostium of the PComA. Based on the initial angiography, patients were divided into two groups: the first with a P1/PComA size ratio >1 (10 cases) and the second with a ratio <=1 (8 cases). Follow-up angiography (mean time of 10 months) showed 90% of PComA flow changes in group 1 but only 12.5% in group 2. There was a significant difference between the two groups (p=0.002). Nevertheless, no patient had new symptoms related to these flow changes during the follow-up period. CONCLUSIONS: In our experience, covering the PComA by FDS when treating carotid siphon aneurysms appeared safe and the P1/PComA ratio is a good predictor of flow changes in PComA. PMID- 27387711 TI - Factors associated with perforator stroke after selective basilar artery angioplasty or stenting. AB - BACKGROUND AND PURPOSE: Perforator stroke is one of the most common complications of elective intracranial angioplasty and/or stenting, particularly in the basilar artery. Factors associated with the risk of post-procedural perforator stroke remain unexplored. We investigated factors affecting the risk of perforator stroke after basilar artery angioplasty and/or stenting. MATERIALS AND METHODS: Consecutive patients undergoing basilar artery angioplasty and/or stenting due to symptomatic atherosclerotic stenosis were retrospectively included in this single center study. Analyzed variables including demographic data, risk factors of atherosclerosis, symptoms, characteristics of imaging, and procedure factors were extracted from electronic health records or imaging data. The main outcome was perforator stroke associated with the procedure. Multivariate analysis that correlated factors with the occurrence of perforator stroke in these patients was performed. RESULTS: A total of 255 patients were included in the study. Perforator stroke associated with angioplasty and/or stenting was identified in 13 patients (5.1%). Variables with significant correlation with post-procedural perforator stroke included diabetes (OR 6.496; 95% CI 1.741 to 24.241; p=0.005), time from last symptom to procedure <18 days (OR 5.669; 95% CI 1.174 to 27.371; p=0.031), and pre-procedure stenosis percentage <88.4% (OR 5.882; 95% CI 1.465 to 23.608; p=0.012). CONCLUSIONS: Diabetes, time from last symptom to procedure, and pre-procedure stenosis percentage may be factors affecting the risk of perforator stroke associated with basilar artery angioplasty and/or stenting. These factors should be considered in planning of potential basilar artery angioplasty and/or stenting and prospectively evaluated in future multicenter trials. PMID- 27387713 TI - Furan-induced transcriptomic and gene-specific DNA methylation changes in the livers of Fischer 344 rats in a 2-year carcinogenicity study. AB - Furan is a significant food contaminant and a potent hepatotoxicant and rodent liver carcinogen. The carcinogenic effect of furan has been attributed to genotoxic and non-genotoxic, including epigenetic, changes in the liver; however, the mechanisms of the furan-induced liver tumorigenicity are still unclear. The goal of the present study was to investigate the role of transcriptomic and epigenetic events in the development of hepatic lesions in Fischer (F344) rats induced by furan treatment in a classic 2-year rodent tumorigenicity bioassay. High-throughput whole-genome transcriptomic analysis demonstrated distinct alterations in gene expression in liver lesions induced in male F344 rats treated with 0.92 or 2.0 mg furan/kg body weight (bw)/day for 104 weeks. Compared to normal liver tissue, 1336 and 1541 genes were found to be differentially expressed in liver lesions in rats treated with 0.92 and 2.0 mg furan/kg bw/day, respectively, among which 1001 transcripts were differentially expressed at both doses. Pairing transcriptomic and next-generation bisulfite sequencing analyses of the common differentially expressed genes identified 42 CpG island-containing genes in which the methylation level was correlated inversely with gene expression. Forty-eight percent of these genes (20 genes, including Areg, Jag1, and Foxe1) that exhibited the most significant methylation and gene expression changes were involved in key pathways associated with different aspects of liver pathology. Our findings illustrate that gene-specific DNA methylation changes have functional consequences and may be an important component of furan hepatotoxicity and hepatocarcinogenicity. PMID- 27387714 TI - Polyvinyl pyrrolidone-coated silver nanoparticles in a human lung cancer cells: time- and dose-dependent influence over p53 and caspase-3 protein expression and epigenetic effects. AB - The present study was aimed at providing a better understanding of the influence of silver nanoparticles (AgNPs) on the p53 tumor suppressor protein. Cell line A549 was exposed to a range of concentrations of AgNPs, and a time course (up to 72 h) of cell viability was determined. We also determined the time course of gene and protein expression of p53, p21, murine double minute 2 (MDM2) and caspase-3. The expression of all of these proteins was also determined after daily exposure of the cells to 10 ug/mL of AgNPs for 7 days, or after discontinuous exposure by treating the cells every 3 days, for 15 or 30 days. Moreover, epigenetic changes in the acetylation of the histone H3 protein and in global DNA methylation patterns were determined after 72 h of exposure. Results showed that daily exposure to low doses of AgNPs, or a single exposure to high concentrations for 72 h, decreased gene and protein expression of p53, p21, MDM2 and caspase-3 in A549 cells. In contrast, a discontinuous exposure to low doses or a single exposure to low concentrations for 72 h increased the levels of the active forms of p53 and caspase-3, as well as the p21 and MDM2 protein levels. In addition, exposure to high concentrations of AgNPs for 72 h induced higher levels of global DNA methylation and global histone H3 deacetylation in A549 cells. These results provide new information on the toxic action of AgNPs. PMID- 27387712 TI - Diagnosing sepsis - The role of laboratory medicine. AB - Sepsis is the host response to microbial pathogens resulting in significant morbidity and mortality. An accurate and timely diagnosis of sepsis allows prompt and appropriate treatment. This review discusses laboratory testing for sepsis because differentiating systemic inflammation from infection is challenging. Procalcitonin (PCT) is currently an FDA approved test to aid in the diagnosis of sepsis but with questionable efficacy. However, studies support the use of PCT for antibiotic de-escalation. Serial lactate measurements have been recommended for monitoring treatment efficacy as part of sepsis bundles. The 2016 sepsis consensus definitions include lactate concentrations >2mmol/L (>18mg/dL) as part of the definition of septic shock. Also included in the 2016 definitions are measuring bilirubin and creatinine to determine progression of organ failure indicating worse prognosis. Hematologic parameters, including a simple white blood cell count and differential, are frequently part of the initial sepsis diagnostic protocols. Several new biomarkers have been proposed to diagnose sepsis or to predict mortality, but they currently lack sufficient sensitivity and specificity to be considered as stand-alone testing. If sepsis is suspected, new technologies and microbiologic assays allow rapid and specific identification of pathogens. In 2016 there is no single laboratory test that accurately diagnoses sepsis. PMID- 27387716 TI - Integrative Mental Health: To the USA from Iceland and Back Again. PMID- 27387715 TI - High platelet reactivity after P2Y12-inhibition in patients with atrial fibrillation and coronary stenting. AB - High platelet reactivity (HPR) after P2Y12-inhibition in patients undergoing coronary stenting is associated with an increased risk for thromboembolic events and coronary death. So far it is not known how HPR affects the clinical outcome of different treatment strategies in patients with atrial fibrillation (AF) undergoing coronary stenting. In this single centre, observational study the antiplatelet effect of P2Y12-inhibitors in AF patients undergoing coronary stenting was investigated using impedance aggregometry. Patients received either dual antiplatelet therapy (DAPT) or triple therapy (TT). HPR was defined as the ratio of ADP-to TRAP-induced aggregation (r-ADP-agg) >=50 %. Thromboembolic and bleeding events were assessed within the first 30 days after stenting. Out of 910 screened patients 167 patients were available for the present analysis. HPR was found in 5 of 43 (12 %) patients treated with DAPT and in 18 of 124 (15 %) patients treated with TT. In patients receiving TT, HPR was not a risk factor for thromboembolic events compared to patients with adequate response to P2Y12 inhibitors (6 vs. 8 %, p = 0.712). There was a trend for less bleeding events in patients with HPR compared to r-ADP-agg <50 % in the TT group (0 vs. 16 %, p = 0.077). Our data suggest that HPR after P2Y12-antagonism in patients receiving TT due to AF and coronary stenting might protect from bleeding without increasing thromboembolic risk. Future studies will need to investigate if patients with AF receiving coronary stenting benefit from a reduction of antithrombotic therapy. PMID- 27387718 TI - Biomechanical evaluation of adjunctive cerclage wire fixation for the prevention of periprosthetic femur fractures using cementless press-fit total hip replacement. AB - Periprosthetic femoral fractures are a common complication associated with cementless press-fit total hip arthroplasty. The use of prophylactic cerclage wire fixation has been advocated to reduce this complication. The objective of this study was to evaluate whether a double loop cerclage wire, used as adjunctive fixation, increased the peak torsional load to failure in femora implanted with press-fit cementless stems. Peak torsional load to failure was compared between femora without adjunctive fixation and femora receiving a 1 mm double loop cerclage wire placed proximally to the lesser trochanter. Femora treated with adjunctive cerclage wire fixation failed at 20% greater peak torque (P = 0.0001). In conclusion, a double loop cerclage wire may aid in the prevention of periprosthetic fractures associated with press-fit cementless femoral stems. PMID- 27387717 TI - Urinary active transforming growth factor beta in feline chronic kidney disease. AB - The cytokine transforming growth factor beta 1 (TGF-beta1) has been widely implicated in the development and progression of renal fibrosis in chronic kidney disease (CKD) in humans and in experimental models. The aims of this study were to assess the association between urinary active TGF-beta1 and (a) development of CKD in a cross-sectional study, (b) deterioration of renal function over 1 year in a longitudinal study, and (c) renal histopathological parameters in cats. A human active TGF-beta1 ELISA was validated for use in feline urine. Cross sectional analysis revealed no significant difference in urinary active TGF beta1:creatinine ratio (aTGF-beta1:UCr) between groups with differing renal function. Longitudinally, non-azotaemic cats that developed CKD demonstrated a significant (P = 0.028) increase in aTGF-beta1:UCr approximately 6 months before the development of azotaemia, which remained elevated (P = 0.046) at diagnosis (approximately 12 months prior, 8.4 pg/mg; approximately 6 months prior, 22.2 pg/mg; at CKD diagnosis, 24.6 pg/mg). In the histopathology study, aTGF-beta1:UCr was significantly higher in cats with moderate (P = 0.02) and diffuse (P = 0.005) renal fibrosis than in cats without fibrosis. Cats with moderate renal inflammation had significantly higher urinary active aTGF-beta1 concentrations than cats with mild (P = 0.035) or no inflammatory change (P = 0.004). The parameter aTGF-beta1:UCr was independently associated with Log urine protein:creatinine ratio in a multivariable analysis of clinicopathological parameters and interstitial fibrosis score in a multivariable analysis of histopathological features. These results suggest that urinary aTGF-beta1 reflects the severity of renal pathology. Increases in urinary aTGF-beta1 followed longitudinally in individual cats may indicate the development of CKD. PMID- 27387719 TI - Experimental infection of conventional pigs with a 'Brachyspira hampsonii' isolate recovered from a migrating waterfowl in Spain. AB - 'Brachyspira hampsonii' is a recently proposed new species within the Brachyspira genus, which produces a dysentery-like disease in pigs. This study aims at investigating whether a 'B. hampsonii' isolate recovered from a migrating waterfowl was capable of colonizing pig intestines, inducing clinical signs of dysentery and being transmitted among pigs. Eleven 7-week-old pigs were randomly assigned into two separate groups which were orally administered an avian isolate of 'B. hampsonii' (inoculated group, n = 5) or BHI broth (control group, n = 6). After inoculation, three pigs from the control group were placed in the inoculated pen and served as sentinel pigs. Our results show the capacity of this avian 'B. hampsonii' isolate to colonize the large intestine of pigs and to be transmitted among pigs. According to this, migrating birds could play a role in the epidemiology of 'B. hampsonii' as a possible source of infection in swine populations. PMID- 27387720 TI - Effect of increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds adapted to cereal-rich or fat-rich meals. AB - The relationships between diet, obesity and insulin dysregulation in equids require further investigation due to their association with laminitis. This study examined the effect of dietary glycaemic load and increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds. Equal numbers of Standardbred horses, mixed-breed ponies and Andalusian horses were provided with ad libitum hay plus either cereal-rich (CHO; n = 12), fat-rich (FAT; n = 12) or control (CON; n = 9) meals over 20 weeks. The isocaloric CHO and FAT diets were fed to induce obesity by gradually increasing the supplementary feeds to provide 200% of daily digestible energy requirements by Week 20. The CON group were fed a basal ration only and maintained moderate body condition. At Week 20, the CHO and FAT groups demonstrated significantly increased body condition score, bodyweight, total body fat mass and plasma leptin concentrations compared with the CON group (P <0.001). The CHO group had lower insulin sensitivity (SI; P <0.001) and higher acute insulin response to glucose (P = 0.002) than the CON group. In contrast, the FAT group was no different to the control group. Ponies and Andalusians had lower SI values compared with Standardbreds, regardless of diet group (P = 0.001). Adiponectin concentrations were similar between the FAT and CON groups, but were significantly lower in the CHO group (P = 0.010). The provision of cereal-rich meals appeared to be a more important determinant of insulin sensitivity than the induction of obesity per se. Whether hypoadiponectinaemia is a cause or consequence of insulin dysregulation warrants further investigation. PMID- 27387721 TI - Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling. AB - Reproductive management is necessary to prevent deleterious genetic disorders in purebred dogs, but comprehensive studies aimed at prevention of multiple underlying genetic disorders in a single breed have not been performed. The aims of this study were to examine mutant allele frequencies associated with multiple genetic disorders, using Border collies as a representative breed, and to make recommendations for prevention of the disorders. Genotyping of known mutations associated with seven recessive genetic disorders was performed using PCR assays. More than half (56%) of the Border collies had no mutant alleles associated with any of the seven disorders, suggesting that these disorders can be removed from the population over several generations. Since frequencies of each mutant allele differed among disorders, reproductive management should be performed after the establishment of prevention schemes that are appropriate for each disorder, the type and specificity of genetic test available, and the effective population size in each breeding colony. PMID- 27387722 TI - Role of the NOD1/NF-kappaB pathway on bovine neutrophil responses to crude lipopolysaccharide. AB - Cytosolic nucleotide oligomerisation domain (NOD)-like receptors play an important role in host defence against infection. Reduced NOD1 expression has been observed in dysfunctional neutrophils derived from periparturient cattle known to be most susceptible to coliform mastitis. However, whether impairment of NOD1 suppresses the immune responses of bovine neutrophils during bacterial infections remains unknown. Crude (phenol extracted) lipopolysaccharide (cLPS), which often contains other immunostimulatory molecules, including NOD1 agonist, is known to induce almost the whole bacterial response. This study was conducted to explore the role of NOD1/nuclear factor (NF)-kappaB pathway in the cytokine and functional responses of bovine neutrophils challenged with Escherichia coli derived cLPS. Freshly isolated blood neutrophils from healthy heifers were pre incubated for 2 h with ML130, a selective inhibitor of NOD1/NF-kappaB pathway. Cells were then exposed to cLPS for additional 4 h. Inhibition of the NOD1/NF kappaB pathway resulted in a decrease in cLPS-induced phosphorylation of the inhibitor of NF-kappaBalpha (IkappaBalpha) in neutrophils. Impairment of the NOD1/NF-kappaB pathway tended to down-regulate mRNA levels of pro-inflammatory cytokines interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha, chemokines IL-8 and C-X-C motif ligand 2 (CXCL2), and adhesion molecules CD11b and CD62L, in cLPS-challenged cells. Functional analyses showed that blocking the NOD1/NF-kappaB pathway inhibited neutrophil migration and phagocytic killing capacity, and promoted neutrophil death upon cLPS stimulation. The data presented here demonstrate that activation of NOD1/NF-kappaB pathway contributes to the functional responses of neutrophils to cLPS. PMID- 27387723 TI - Influences on antimicrobial resistance: More than bugs and drugs. PMID- 27387724 TI - The incidence and risk factors for shipping fever in horses transported by air to Hong Kong: Results from a 2-year prospective study. AB - A 2 year prospective study was performed between February 2011 and January 2013 to determine the incidence and risk factors for shipping fever (SF) in horses transported by air to Hong Kong (HK). Using a questionnaire, data were collected from professional flying grooms regarding the journey to HK and horses in the shipment. Horses were monitored in quarantine for 2 weeks after arrival in HK, and clinical signs of SF recorded. Poisson and logistic regression models were used to identify risk factors for SF at the horse and shipment levels. The study analysed data from 869 horses on 81 flights arriving from Australia (n = 24), New Zealand (NZ; n = 18), the United Kingdom (UK; n = 33) and the United States of America (USA; n = 6). The incidence risk of SF was 10.8 per 100 horses and the proportion of shipments with at least one horse that developed SF was 49/81 (60%). The study identified that the rate per shipment of SF in shipments of horses originating from NZ, the USA and the UK was 2.40 (95% confidence interval [CI] 1.22-4.71), 2.43 (95% CI 0.66-8.89) and 3.08 (95% CI 1.60-5.93) times the rate of SF compared to Australia. Shipments arriving in HK during March and May were 5.61 (95% CI 1.55-20.31) and 4.51 (95% CI 1.43-14.26) times more likely to contain horses that developed SF compared to shipments arriving in January. The identification of these risk factors and the recognition of at-risk shipments will help focus attention on preventative strategies. PMID- 27387725 TI - Experimental infection of chickens by a flagellated motile strain of Salmonella enterica serovar Gallinarum biovar Gallinarum. AB - Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid (FT), a septicaemic disease which can result in high mortality in poultry flocks. The absence of flagella in SG is thought to favour systemic invasion, since bacterial recognition via Toll-like receptor (TLR)-5 does not take place during the early stages of FT. In the present study, chicks susceptible to FT were inoculated with a wild type SG (SG) or its flagellated motile derivative (SG Fla(+)). In experiment 1, mortality and clinical signs were assessed, whereas in experiment 2, gross pathology, histopathology, systemic invasion and immune responses were evaluated. SG Fla(+) infection resulted in later development of clinical signs, lower mortality, lower bacterial numbers in the liver and spleen, and less severe pathological changes compared to SG. The CD8(+) T lymphocyte population was higher in the livers of chicks infected with SG at 4 days post-inoculation (dpi). Chicks infected with SG had increased expression of interleukin (IL)-6 mRNA in the caecal tonsil at 1 dpi and increased expression of IL-18 mRNA in the spleen at 4 dpi. In contrast, the CD4(+) T lymphocyte population was higher at 6 dpi in the livers of birds infected with SG Fla(+). Therefore, flagella appeared to modulate the chicken immune response towards a CD4(+) T profile, resulting in more efficient bacterial clearance from systemic sites and milder infection. PMID- 27387726 TI - Influence of short distance transportation on tracheal bacterial content and lower airway cytology in horses. AB - The aim of this study was to determine the effects of short distance transportation on airway mucus, cytology and bacterial culture to identify potential biases in the diagnosis of airway diseases in referral centres. Eight healthy adult horses were studied using a prospective cross-over design. Mucus scores, tracheal wash (cytology, bacterial culture) and bronchoalveolar lavage fluid (BALF; cytology) were obtained while stabled and following 2.5 h transportation (with and without hay). Neutrophil counts, percentages and BALF neutrophilia frequency increased following transport without hay (P <0.05). No effect was observed on tracheal cytology and bacterial count (P > 0.05). BALF neutrophilia could develop solely as a result of transportation or due to interactions between repeated transports, ambient temperature, head position or other environmental factors. PMID- 27387727 TI - Maximizing the diagnostic utility of endoscopic biopsy in dogs and cats with gastrointestinal disease. AB - Flexible endoscopy has become a valuable tool for the diagnosis of many small animal gastrointestinal (GI) diseases, but the techniques must be performed carefully so that the results are meaningful. This article reviews the current diagnostic utility of flexible endoscopy, including practical/technical considerations for endoscopic biopsy, optimal instrumentation for mucosal specimen collection, the correlation of endoscopic indices to clinical activity and to histopathologic findings, and new developments in the endoscopic diagnosis of GI disease. Recent studies have defined endoscopic biopsy guidelines for the optimal number and quality of diagnostic specimens from different regions of the gut. They also have shown the value of ileal biopsy in the diagnosis of canine and feline chronic enteropathies, and have demonstrated the utility of endoscopic biopsy specimens beyond routine hematoxylin and eosin histopathological analysis, including their use in immunohistochemical, microbiological, and molecular studies. PMID- 27387728 TI - Cartilage defect repair in horses: Current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach. AB - Chondral and osteochondral lesions due to injury or other pathology are highly prevalent conditions in horses (and humans) and commonly result in the development of osteoarthritis and progression of joint deterioration. Regenerative medicine of articular cartilage is an emerging clinical treatment option for patients with articular cartilage injury or disease. Functional articular cartilage restoration, however, remains a major challenge, but the field is progressing rapidly and there is an increasing body of supportive clinical and scientific evidence. This review gives an overview of the established and emerging surgical techniques employed for cartilage repair in horses. Through a growing insight in surgical cartilage repair possibilities, surgeons might be more stimulated to explore novel techniques in a clinical setting. PMID- 27387729 TI - Use of diagnostic reports to estimate prevalence and distribution of skeletal lesions in young Thoroughbreds. AB - Diagnostic reports written to assist stud managers in the sale of young Thoroughbreds have not previously been used as a data source for the study of skeletal lesions. However, analyses of these reports may provide efficient and cost-effective insights into the prevalence and distribution of skeletal lesions within a population. Diagnostic reports written by veterinarians were acquired from Thoroughbred stud managers in Australia and New Zealand. The reports were based on approximately 1300 sets of weanling and yearling radiographs taken between 2002 and 2007. The prevalence and anatomical distribution of skeletal lesions in weanlings (299 horses) and yearlings (1004 horses) were determined from these reports. Overall, 69.9% of weanlings and 64.5% of yearlings were reported as having one or more skeletal lesions. Diagnostic reports in weanlings were a strong indication of what was likely to be seen in subsequent yearling reports. These diagnostic reports are typically used by stud managers in the sales process and the potential drawback is that some categories of skeletal lesions may be under-reported. However, there was substantial agreement between the prevalence and distribution of several skeletal lesions reported in this study and those previously reported from direct evaluation of radiographs for Australian and New Zealand Thoroughbred yearlings. Strong agreement was found for osteophytes, enthesiophytes and other modelling in the hocks, and for lesions in the hind fetlocks and stifles. This indicates that written diagnostic reports are a useful and a reliable source of data for the study of some skeletal lesions in young Thoroughbred horses. PMID- 27387730 TI - Hybrid vigour in dogs? AB - Evidence from other species justifies the hypotheses that useful hybrid vigour occurs in dogs and that it can be exploited for improved health, welfare and fitness for purpose. Unfortunately, most of the relevant published canine studies do not provide estimates of actual hybrid vigour because of inadequate specification of the parentage of mixed-bred dogs. To our knowledge, only three published studies have shed any light on actual hybrid vigour in dogs. There are two reports of actual hybrid vigour between Labrador and Golden retrievers, the first ranging from +2.5% to -6.0% for components of a standardised applied stimulus behavioural test, and the second being at least +12.4% for chance of graduating as a guide dog. The third study provides a minimum estimate of negative actual hybrid vigour: crossbreds between Labrador retrievers and poodles had a higher prevalence of multifocal retinal dysplasia than the average prevalence in their purebred parent breeds. The lack of estimates of actual hybrid vigour can be overcome by including the exact nature of the cross (e.g. F1, F2 or backcross) and their purebred parental breeds in the specification of mixed-bred dogs. Even if only F1 crossbreds can be categorised, this change would enable researchers to conduct substantial investigations to determine whether hybrid vigour has any utility for dog breeding. PMID- 27387731 TI - Transcriptional profiling of canine mast cell tumors: Searching for candidate targets and prognostic markers. PMID- 27387732 TI - Influence of glucocorticoids on a time-of-day-dependent variation in intradermal reactivity to histamine in dogs. AB - The objectives of this study were to determine daily variation in intradermal reactivity to histamine in dogs and to evaluate a potential influence of glucocorticoids on reactivity. Wheal sizes formed after intradermal injections of histamine were measured every 6 h during a single 24 h period in six healthy dogs. To determine whether glucocorticoids were implicated in daily variation, intradermal reactivity to histamine was evaluated at 9:00 h and at 21:00 h during a single day in dogs that received oral prednisolone (a synthetic glucocorticoid) or oral trilostane (an inhibitor of endogenous glucocorticoid synthesis). Finally, the time required for the histamine reaction to diminish after an intravenous injection of hydrocortisone was also assessed. A significant time-of day-dependent variation in intradermal reactivity to histamine was detected in dogs, with a larger wheal size observed at 9:00 h than at 21:00 h. Administration of prednisolone or trilostane disrupted this variation. Intradermal reactivity to histamine was significantly reduced 6 h after an intravenous injection of hydrocortisone. These results suggest that glucocorticoid secretion from the adrenal glands could be involved in the regulation of daily variation in histamine-mediated reactions in dogs. PMID- 27387733 TI - Prognostic factors for 1-week survival in dogs diagnosed with meningoencephalitis of unknown aetiology. AB - Although long-term outcomes of meningoencephalitis of unknown aetiology (MUA) in dogs have been evaluated, little is known about short-term survival and initial response to therapy. The aim of this study was to evaluate possible prognostic factors for 7-day survival after diagnosis of MUA in dogs. Medical records were reviewed for dogs diagnosed with MUA between 2006 and 2015. Previously described inclusion criteria were used, as well as 7-day survival data for all dogs. A poor outcome was defined as death within 1 week. Of 116 dogs that met inclusion criteria, 30 (26%) died within 7 days of diagnosis. Assessed variables included age, sex, bodyweight, duration of clinical signs and treatment prior to diagnosis, venous blood glucose and lactate levels, white blood cell count on complete blood count, total nucleated cell count/total protein concentration/white blood cell differentiation on cerebrospinal fluid (CSF) analysis, presence of seizures and cluster seizures, mentation at presentation, neuroanatomical localisation, imaging findings and treatment after diagnosis. Multivariate analysis identified three variables significantly associated with poor outcome; decreased mentation at presentation, presence of seizures, and increased percentage of neutrophils on CSF analysis. Despite initiation of appropriate treatment, more than a quarter of dogs died within 1 week of diagnosis of MUA, emphasising the need for evaluation of short-term prognostic factors. Information from this study could aid clinical staff to provide owners of affected dogs with prognostic information. PMID- 27387734 TI - In vitro assessment of the antimicrobial susceptibility of caprine isolates of Mycoplasma mycoides subsp. capri. AB - The minimum inhibitory concentration (MIC) and minimum mycoplasmacidal concentration (MMC) of 17 antimicrobials against 41 Spanish caprine isolates of Mycoplasma mycoides subsp. capri (Mmc) obtained from different specimens (milk, external auricular canal and semen) were determined using a liquid microdilution method. For half of the isolates, the MIC was also estimated for seven of the antimicrobials using an epsilometric test (ET), in order to compare both methods and assess the validity of ET. Mutations in genes gyrA, gyrB, parC and parE conferring fluoroquinolone resistance, which have been recently described in Mmc, were investigated using PCR. The anatomical origin of the isolate had no effect on its antimicrobial susceptibility. Moxifloxacin and doxycycline had the lowest MIC values. The rest of the fluoroquinolones studied (except norfloxacin), together with tylosin and clindamycin, also had low MIC values, although the MMC obtained for clindamycin was higher than for the other antimicrobials. For all the aminoglycosides, spiramycin and erythromycin, a notable level of resistance was observed. The ET was in close agreement with broth microdilution at low MICs, but not at intermediate or high MICs. The analysis of the genomic sequences revealed the presence of an amino acid substitution in codon 83 of the gene gyrA, which has not been described previously in Mmc. PMID- 27387735 TI - Mechanical nociceptive thresholds of dorsal laminae in horses after local anaesthesia of the palmar digital nerves or dorsal branches of the digital nerve. AB - We examined the hypothesis that the palmar digital nerves (PDNs), but not the dorsal branches (DBs) of the digital nerves, innervate the sensitive dorsal laminae of the equine foot by evaluating the effects of perineural anaesthesia of the PDNs and DBs separately on pain sensation evoked via mechanical stimulation of the dorsal laminae and other regions of the equine foot. Six clinically normal mares were used in a crossover design. A portable dynamometer was used to evaluate mechanical nociceptive thresholds at different points on the dorsal laminae, bulbs of the heel, coronary band and sole before and after the horses underwent perineural injection of PDNs or DBs with a local anaesthetic solution (treated group) or an isotonic saline solution (control group). Cornified tissue was removed from the sole and the dorsal aspect of the hoof wall before evaluations of mechanical nociceptive thresholds. Anaesthetising PDNs distal to the DBs increased mechanical nociceptive thresholds compared to baseline values (P <0.001) at sites assessed in the dorsal laminae, sole, and the bulbs of the heels. Anaesthetising DBs increased mechanical nociceptive thresholds compared to baseline values (P <0.01) only at sites assessed at the most proximal aspect of the foot (i.e., coronary band sites). In conclusion, PDNs, not DBs, are primarily responsible for pain signal transmission evoked by pressure in the dorsal laminae of the foot of clinically normal horses. PMID- 27387736 TI - Classification of involuntary movements in dogs: Tremors and twitches. AB - This review focuses on important new findings in the field of involuntary movements (IM) in dogs and illustrates the importance of developing a clear classification tool for diagnosing tremor and twitches. Developments over the last decade have changed our understanding of IM and highlight several caveats in the current tremor classification. Given the ambiguous association between tremor phenomenology and tremor aetiology, a more cautious definition of tremors based on clinical assessment is required. An algorithm for the characterisation of tremors is presented herein. The classification of tremors is based on the distinction between tremors that occur at rest and tremors that are action related; tremors associated with action are divided into postural or kinetic. Controversial issues are outlined and thus reflect the open questions that are yet to be answered from an evidence base of peer-reviewed published literature. Peripheral nerve hyper-excitability (PNH; cramps and twitches) may manifest as fasciculations, myokymia, neuromyotonia, cramps, tetany and tetanus. It is anticipated that as we learn more about the aetiology and pathogenesis of IMs, future revisions to the classification will be needed. It is therefore the intent of this work to stimulate discussions and thus contribute to the development of IM research. PMID- 27387737 TI - High prevalence of Felis catus gammaherpesvirus 1 infection in haemoplasma infected cats supports co-transmission. AB - Felis catus gammaherpesvirus 1 (FcaGHV1), a potential feline pathogen, has been identified in domestic cats from USA, Asia-Pacific and Central Europe. Transmission of FcaGHV1 during territorial encounters, a route not typical for gammaherpesviruses, is suggested by risk factor analyses from some regions. The aim of this study was to investigate the relationship between FcaGHV1 detection and risk factors, including haemoplasma co-infections, among UK cats to better understand transmission and global distribution of FcaGHV1. FcaGHV1 DNA was detected in blood samples from UK cats (11.56%; 95% confidence interval [CI], 7.47-16.84; n = 199). Logistic regression analyses showed that entire male cats were more likely to be FcaGHV1 positive than neutered male cats (odds ratio, 3.60; 95% CI, 1.22-10.46). Samples positive for DNA from any of three haemoplasma species had 19 times greater odds for testing positive for FcaGHV1 than haemoplasma negative cats in multivariable analyses after adjusting for age, sex and neuter status. Domestic cats in the UK can be infected with FcaGHV1, confirming that this virus is globally endemic. The identification of neuter status as a risk factor for FcaGHV1 detection provides further evidence to support transmission of this virus during territorial encounters and co transmission with haemoplasmas is suggested. PMID- 27387738 TI - Cross-calibration of the Siemens mMR: easily acquired accurate PET phantom measurements, long-term stability and reproducibility. AB - BACKGROUND: We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water phantom. LONG-TERM STABILITY: The mMR calibration stability was evaluated over a 3-year period where 54 cross-calibrations were acquired, showing that the mMR on average underestimated the concentration by 16 %, consistently due to the use of MR-based MU-maps. The mMR produced the narrowest calibration ratio range with the lowest standard deviation, implying it is the most stable of the six systems in the study over a 3-year period. MMR ACCURACY WITH PREDEFINED MU-MAPS: With the latest mMR software version, VB20P, it is possible to utilize predefined phantom MU maps. We evaluated both the system-integrated, predefined MU-map of the long mMR water phantom and our own user-defined CT-based MU-map of the mCT water phantom, which is used for cross-calibration. For seven scans, which were reconstructed with correctly segmented MU-maps, the mMR produced cross-calibration ratios of 1.00-1.02, well within the acceptance range [0.95-1.05], showing high accuracy. CONCLUSIONS: The mMR is the most stable PET system in this study, and the mean underestimation is no longer an issue with the easily accessible MU-map, which resulted in correct cross-calibration ratios in all seven tests. We will share the user-defined MU-map of the mCT phantom and the protocol with interested mMR users. PMID- 27387739 TI - Postpartum IGF-I and IGFBP-2 levels are prospectively associated with the development of type 2 diabetes in women with previous gestational diabetes mellitus. AB - AIMS: Women with previous gestational diabetes mellitus (GDM) are at greater risk of developing type 2 diabetes. In the general population, the insulin-like growth factor (IGF) system has been implicated in the development of type 2 diabetes. The aim of this study was to determine if circulating IGF-I, IGF-II, IGFBP-1 and IGFBP-2 levels 12weeks following a GDM pregnancy are associated with an increased risk of developing type 2 diabetes. METHODS: IGF-I, IGF-II, IGFBP-1 and IGFBP-2 levels were measured in 98 normal glucose tolerant women, 12weeks following an index GDM pregnancy using enzyme immunoassay. Women were assessed for up to 10years for the development of overt type 2 diabetes. RESULTS: Among the 98 women with previous GDM, 21 (21%) developed diabetes during the median follow-up period of 8.5years. After adjusting for age and BMI, IGF-I and IGFBP-2 were significantly associated with the development of type 2 diabetes. In a clinical model of prediction of type 2 diabetes that included age, BMI, pregnancy fasting glucose and postnatal fasting glucose, the addition of IGF-I and IGFBP-2 resulted in an improvement in the net reclassification index of 17.8%. CONCLUSIONS: High postpartum IGF-I and low postpartum IGFBP-2 levels are a significant risk factor for the development of type 2 diabetes in women with a previous history of GDM. This is the first report that identifies IGF-I and IGFBP-2 as a potential biomarker for the prediction of type 2 diabetes in women with a history of GDM. PMID- 27387740 TI - MUW researcher of the month. PMID- 27387742 TI - Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs. AB - BACKGROUND: The efficacy of fluralaner, formulated as a chewable tablet (BravectoTM) or topical solution (BravectoTM Spot-on Solution), was evaluated against naturally acquired Sarcoptes scabiei var. canis infestation in dogs. METHODS: The study was performed in privately-owned dogs naturally infested with S. scabiei var. canis. All dogs living in the same household as the infested dog were enrolled into one of 3 groups (2 fluralaner treated and 1 negative control). All dogs within one household were administered the same treatment, with one dog per household included in further observations and assessments. In total, 29 dogs confirmed positive for sarcoptic mange were included. On Day 0, all dogs in group 1 (n = 9) were treated once orally with fluralaner at a minimum dose of 25 mg/kg body weight; all dogs in group 2 (n = 11) were treated once topically with fluralaner at a dose of 25 mg/kg body weight; and dogs in group 3 (n = 9) were treated once topically with saline solution. Sarcoptes scabiei var. canis mites on each dog were counted before treatment and at 4 weeks after treatment in deep skin scrapings (~4 cm(2)) from 5 different body areas. Clinical signs of infestation (i.e. erythematous papules; casts, scales and crusts; body areas with hair loss) and pruritus were recorded at the same time points. RESULTS: Single oral or topical treatment with fluralaner resulted in a 100 % reduction in mite counts post-treatment (group 1: P = 0.0009 and group 2: P = 0.0011). Resolution of clinical signs at four weeks post-treatment was variable, with improvement observed for erythematous papules, casts and crusts, and pruritus. All fluralaner treated dogs showed an improvement in overall hair re-growth compared with pre treatment observations. CONCLUSION: Fluralaner administered either orally or topically to naturally infested dogs eliminates Sarcoptes scabiei var. canis mites and improves clinical signs over a 4-week observation period. PMID- 27387741 TI - Quality of life following hip fractures: results from the Norwegian hip fracture register. AB - BACKGROUND: Patient-reported health-related quality of life is an important outcome measure when assessing the quality of hip fracture surgery. The frequently used EQ-5D index score has unfortunately important limitations. One alternative can be to assess the distribution of each of the five dimensions of the patients' descriptive health profile. The objective of this paper was to investigate health-related quality of life (HRQoL) after hip fractures. METHODS: Data from hip fracture operations from 2005 through 2012 were obtained from The Norwegian Hip Fracture Register. Patient reported HRQoL, (EQ-5D-3L) was collected from patients preoperatively and at four and twelve months postoperatively n = 10325. At each follow-up the distribution of the EQ-5D-3L and mean pain VAS was calculated. RESULTS: Generally, a higher proportion of patients reported problems in all 5 dimensions of the EQ-5D-3L at all follow-ups compared to preoperative. Also a high proportion of patients with no preoperative problems reported problems after surgery; At 4 and 12 months follow-ups 71 % and 58 % of the patients reported walking problems, and 65 % and 59 % of the patients reported pain respectively. Patients with femoral neck fractures and the youngest patients (age < 70 years) reported least problems both preoperatively and at all follow ups. CONCLUSIONS: A hip fracture has a dramatic impact on the patients' HRQoL, and the deterioration in HRQoL sustained also one year after the fracture. Separate use of the descriptive profile of the EQ-5D is informative when assessing quality of life after hip fracture surgery. PMID- 27387744 TI - Dietary and economic effects of eliminating shortfall in fruit intake on nutrient intakes and diet cost. AB - BACKGROUND: Children in the United States do not consume the recommended amounts of fruit. The economic and dietary consequences of meeting the shortfall in fruit consumption have not been evaluated. METHODS: Analyses were based on a nationally representative sample of 4-18 year-old children (n = 2,647) from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). The shortfall in total fruit consumption for each child was estimated based on the USDA MyPlate recommendations. The potential impact of filling the shortfall in total fruit consumption was projected with whole fruit alone (WF model) or a combination of 100 % fruit juice and whole fruit (FJ + WF model). Juice consumption was capped using American Academy of Pediatrics (AAP) standards. The USDA national food prices database was used to estimate the cost of meeting the dietary recommendations for fruit. Selected nutrient and mineral intakes, as well as daily diet cost were estimated after eliminating the shortfall in fruit consumption. RESULTS: Among all children, vitamin C (+22.8 mg [95 % CI 21.4, 24.1] in the WF model and +48.1 mg [95 % CI 45.2, 51.1] in the FJ + WF model) and potassium intakes (+203 mg [95 % CI 190, 215] in WF and +263 mg [95 % CI 248, 280] in FJ + WF) were increased in both models. The FJ + WF model resulted in a marginal increase in dietary fiber (e.g., a relative change less than 10 %), while the WF model resulted in a meaningful increase in dietary fiber (e.g., a relative change greater than 10 %; +2.2 g [95 % CI 2.1, 2.3]). Conversely, the WF model resulted in only a marginal increase in calcium, while the FJ + WF model resulted in a meaningful increase in calcium (+85 mg [95 % CI 79, 89]). Calories were increased in all models (+4.5 % [95 % CI 4.1, 4.9 %] for FJ + WF and +3.5 % [95 % CI 3.2, 3.7 %] for WF). Meeting the fruit shortfall with whole fruit alone increased estimated diet costs by 9.9 % (+$0.44/d [95 % CI 0.42, 0.47]), while the fruit juice/whole fruit combination increased diet costs by 5.2 % (+$0.23/d [95 % CI 0.22, 0.25]). CONCLUSIONS: Meeting fruit consumption guidelines without a substantial increase in diet costs may be a challenge. Combining whole fruit with 100 % fruit juice capped at AAP standards may be one approach to meeting fruit recommendations within cost constraints. Identifying approaches to increasing whole fruit consumption in as cost-neutral a fashion as possible should be a priority. PMID- 27387745 TI - Site-Specific Chemical Surface Functionalization and Electronic Patterning of Graphene by Electrooxidative Lithography. AB - The combination of different properties being manipulated on nanomaterials is one of the challenges in nanotechnology research. In particular, the possibility to tailor the electronic and chemical properties offers promising possibilities for the design of functional nanostructures. Herein, we report an approach that permits control of these properties on the basis of electrooxidative lithography to structure reduced graphene oxide functionalized with a self-assembled monolayer of n-octadecyltrichlorosilane. The electrochemical oxidation process first induces the formation of polar acid groups on the monolayer, which can be used to covalently bind nanoparticles and molecules and, secondly, also allows the reoxidation of the underlying reduced graphene oxide. As such, the chemical signature as well as the electronic properties of the substrate can be tailored on the micro- and nanometer scale. Details on the oxidation of the monolayer as well as thorough characterization of the electronic properties will be presented. Finally, the approach is used to demonstrate the fabrication of a sensitive glucose sensor device. PMID- 27387746 TI - No Do-Overs. PMID- 27387747 TI - Comment on "Normalizing Rejection". PMID- 27387743 TI - Detection of circulating tumor cells using manually performed immunocytochemistry (MICC) does not correlate with outcome in patients with early breast cancer - Results of the German SUCCESS-A- trial. AB - BACKGROUND: Recently, the prognostic significance of circulating tumor cells (CTCs) in primary breast cancer as assessed using the Food-and-Drug Administration-approved CellSearch(r) system has been demonstrated. Here, we evaluated the prognostic relevance of CTCs, as determined using manually performed immunocytochemistry (MICC) in peripheral blood at primary diagnosis, in patients from the prospectively randomized multicenter SUCCESS-A trial (EudraCT2005000490-21). METHODS: We analyzed 23 ml of blood from 1221 patients with node-positive or high risk node-negative breast cancer before adjuvant taxane-based chemotherapy. Cells were separated using a density gradient followed by epithelial cell labeling with the anti-cytokeratin-antibody A45-B/B3, immunohistochemical staining with new fuchsin, and cytospin preparation. All cytospins were screened for CTCs, and the cutoff for positivity was at least one CTC. The prognostic value of CTCs with regard to disease-free survival (DFS), distant disease-free survival (DDFS), breast-cancer-specific survival (BCSS), and overall survival (OS) was assessed using both univariate analyses applying the Kaplan-Meier method and log-rank tests, and using multivariate Cox regressions adjusted for other predictive factors. RESULTS: In 20.6 % of all patients (n = 251) a median of 1 (range, 1-256) CTC was detected, while 79.4 % of the patients (n = 970) were negative for CTCs before adjuvant chemotherapy. A pT1 tumor was present in 40.0 % of patients, 4.8 % had G1 grading and 34.6 % were node negative. There was no association between CTC positivity and tumor stage, nodal status, grading, histological type, hormone receptor status, Her2 status, menopausal status or treatment. Univariate survival analyses based on a median follow-up of 64 months revealed no significant differences between CTC-positive and CTC-negative patients with regard to DFS, DDFS, BCSS, or OS. This was confirmed by fully adjusted multivariate Cox regressions, showing that the presence of CTCs (yes/no) as assessed by MICC did not predict DFS, DDFS, BCSS or OS. CONCLUSIONS: We could not demonstrate prognostic relevance regarding CTCs that were quantified using the MICC method at the time of primary diagnosis in our cohort of early breast cancer patients. Further studies are necessary to evaluate if the presence of CTCs assessed using MICC has prognostic relevance, or can be used for risk stratification and treatment monitoring in adjuvant breast cancer. TRIAL REGISTRATION: The ClinicalTrial.gov registration ID of this prospectively randomized trial is NCT02181101 ; the (retrospective) registration date was June 2014 (study start date September 2005). PMID- 27387748 TI - Midwest Nursing Research Society News. PMID- 27387749 TI - 10th anniversary of iPS cells: the challenges that lie ahead. AB - In 2006, induced pluripotent stem (iPS) cells were generated by Yamanaka and Takahashi for the first time from a mouse fibroblast culture by introducing four factors. In the 10 years since then, this breakthrough discovery has been making waves in the fields of biology and medical science. For example, various technologies for generating iPS cells have been developed, and we have cultivated a better understanding of the mechanisms involved in reprogramming. In addition, many researchers have explored the applications of iPS cells, such as drug discovery, the study of disease mechanisms and regenerative medicine, and the development of advanced technologies for the differentiation and qualification of the cells. Furthermore, the concept of iPS cell generation has inspired a number of studies that do not use iPS cells. We herein review and discuss the past, present and future of iPS cells and their related issues. PMID- 27387750 TI - Serine racemase is involved in d-aspartate biosynthesis. AB - d-Aspartate is found in the nervous and reproductive system and participates in various physiological roles. While several lines of evidence suggest that this amino acid has an endogenous origin, the enzyme responsible for mammalian d-Asp biosynthesis has not yet been identified. We show that mammalian serine racemase (SRR), the primary enzyme responsible for brain d-Ser production, catalyses Asp racemization via a two-base mechanism. We observed that overexpression of SRR in rat pheochromocytoma PC12 cells resulted in an increase in intracellular d-Asp compared with control cells, demonstrating that SRR functions as an Asp racemase in the cells. To investigate the impact of endogenous SRR on endogenous d-Asp levels in the cells, we generated SRR-knockout (SRR-KO) PC12 cells. The SRR-KO cells exhibited decreased intracellular d-Ser levels, but production levels of d Asp were unaffected. In contrast, SRR-KO mice showed significantly decreased d Asp levels in their frontal cortices and hippocampi, where SRR is normally highly expressed, while d-Asp levels in the cerebellum and testes remained unchanged. Our results indicate that SRR indeed acts as a d-Asp biosynthetic enzyme in some organs and/or tissues, and also provide evidences that there should be some additional enzyme for d-Asp synthesis in mammals. PMID- 27387751 TI - The double knockout of Bach1 and Bach2 in mice reveals shared compensatory mechanisms in regulating alveolar macrophage function and lung surfactant homeostasis. AB - Pulmonary alveolar proteinosis (PAP) is a disease resulting from a dysfunction of the alveolar macrophages (AMs) where excess surfactant protein accumulates in the alveolar spaces. We previously reported that Bach2 KO mice developed PAP due to a defect in the handling of lipids by AMs. To investigate the functions of Bach1 and Bach2, which are regulated by oxidative stress, in the AMs and in lung homeostasis, we generated mice that lacked both Bach1 and Bach2 (Bach1/2 DKO mice). The Bach1/2 DKO mice showed more severe PAP phenotype than Bach2 KO mice with abnormal AMs, whereas the Bach1 KO mice did not develop any pulmonary disease. The PAP-like disease in the Bach1/2 DKO and Bach2 KO mice was not ameliorated by antioxidant, suggesting that ROS was not involved in the onset of PAP in the absence of Bach1 and Bach2. A microarray and a chromatin immunoprecipitation sequence analysis revealed that Bach1 and Bach2 directly repress the common set of genes involved in the inflammatory response, and that Bach2 is a major contributor to this repression. These results suggest that Bach1 and Bach2 work in a complementary manner to maintain the normal function of the AMs and surfactant homeostasis in the lung. PMID- 27387752 TI - Telemedicine-supported transition of stable coronary artery disease patients from tertiary to primary health care facilities: protocol for a randomized non inferiority trial. AB - BACKGROUND: Many Brazilian patients with complex diseases who are treated in tertiary referral clinics have been stable for long periods. The main needs of these patients involve monitoring of risk factors and review of drug prescriptions, which could be satisfactorily done in primary care facilities. The goal of this protocol is to evaluate the safety and effectiveness of telemedicine services to support the transition of patients with stable chronic coronary artery disease from the tertiary to the primary level of care. METHODS/DESIGN: We designed a randomized non-inferiority protocol that will include 280 patients with stable coronary artery disease (for at least 12 months). Patients will be selected from the Ischemic Heart Disease Clinic in a tertiary care hospital in southern Brazil. Enrolled participants will be randomized into one of two groups: 12 months of follow-up at the same clinic; or 12 months of follow-up at a primary care facility with clinical support from a telemedicine platform including a toll free line for physicians (intervention group). In the intervention group, decisions to refer patients to tertiary care during follow-up will be made jointly by primary physicians and medical teleconsultants. The groups will be compared in terms of the primary outcome-maintenance of baseline functional class 1 or 2 after 12 months. Secondary outcomes include control of risk factors and instability of the disease. DISCUSSION: We intend to determine the effectiveness of using telemedicine to qualify the transition of patients with chronic coronary disease from the tertiary to the primary level of care. This should facilitate the access of patients to the healthcare system, since care will be provided closer to their homes, and provide more opportunities for treatment of severe cases at tertiary care hospitals that are often overcrowded. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02489565 - trial registration date May 13, 2015. PMID- 27387754 TI - Physical activity in children with Juvenile Idiopathic Arthritis compared to controls. AB - BACKGROUND: To compare physical activity (PA) in children with juvenile idiopathic arthritis (JIA) with controls and to analyse the effect of disease specific factors on PA in children with JIA treated according to current treatment regimes. METHODS: PA was measured with a 7-day activity diary and expressed as physical activity level (PAL). Moderate to vigorous physical activity (MVPA) (hours/day) and sedentary time (hours/day) was determined. In children with JIA, medication, the number of swollen and/or painful joints, disease activity, functional ability, pain and well-being was determined. Multivariate regression analysis was performed to analyze differences in PA between JIA and controls, adjusted for influences of age, gender, season, Body Mass Index (BMI) and to analyze predictors of PA in JIA patients. RESULTS: Seventy-six children with JIA (26 boys and 50 girls, mean +/- SD age 10.0 +/- 1.4 years) and 131 controls (49 boys and 82 girls, mean +/- SD age 10.4 +/- 1.2 years) participated in this study. Children with JIA had a significantly lower PAL (0.10, p = 0.01) corrected for age, BMI, gender and season. They spent less time in MVPA (0.41 h/day, p = 0.06) and had a significantly higher mean time spent in sedentary activities (0.59 h/day, p 0.02) compared to controls. The activity level of children with JIA was related to age, gender, season, feeling of well-being and pain. CONCLUSION: Children with JIA have a lower PAL, spent less time in MVPA and spent more time on sedentary activities compared to controls despite current medical treatment and PA encouragement. TRIAL REGISTRATION: Data of the children with JIA are from the Rheumates@work study ISRCTN92733069 . PMID- 27387755 TI - Molecular Characterization of Cryptosporidium Species and Giardia duodenalis from Symptomatic Cambodian Children. AB - BACKGROUND: In a prospective study, 498 single faecal samples from children aged under 16 years attending an outpatient clinic in the Angkor Hospital for Children, northwest Cambodia, were examined for Cryptosporidium oocysts and Giardia cysts using microscopy and molecular assays. METHODOLOGY/PRINCIPAL FINDINGS: Cryptosporidium oocysts were detected in 2.2% (11/498) of samples using microscopy and in 7.7% (38/498) with molecular tests. Giardia duodenalis cysts were detected in 18.9% (94/498) by microscopy and 27.7% (138/498) by molecular tests; 82% of the positive samples (by either method) were from children aged 1 10 years. Cryptosporidium hominis was the most common species of Cryptosporidium, detected in 13 (34.2%) samples, followed by Cryptosporidium meleagridis in 9 (23.7%), Cryptosporidium parvum in 8 (21.1%), Cryptosporidium canis in 5 (13.2%), and Cryptosporidium suis and Cryptosporidium ubiquitum in one sample each. Cryptosporidium hominis and C. parvum positive samples were subtyped by sequencing the GP60 gene: C. hominis IaA16R6 and C. parvum IIeA7G1 were the most abundant subtypes. Giardia duodenalis was typed using a multiplex real-time PCR targeting assemblages A and B. Assemblage B (106; 76.8% of all Giardia positive samples) was most common followed by A (12.3%) and mixed infections (5.1%). Risk factors associated with Cryptosporidium were malnutrition (AOR 9.63, 95% CI 1.67 55.46), chronic medical diagnoses (AOR 4.51, 95% CI 1.79-11.34) and the presence of birds in the household (AOR 2.99, 95% CI 1.16-7.73); specifically C. hominis (p = 0.03) and C. meleagridis (p<0.001) were associated with the presence of birds. The use of soap was protective against Giardia infection (OR 0.74, 95% CI 0.58-0.95). CONCLUSIONS/SIGNIFICANCE: This is the first report to describe the different Cryptosporidium species and subtypes and Giardia duodenalis assemblages in Cambodian children. The variety of Cryptosporidium species detected indicates both anthroponotic and zoonotic transmission in this population. Interventions to improve sanitation, increase hand washing after defecation and before preparing food and promote drinking boiled water may reduce the burden of these two parasites. PMID- 27387756 TI - Development of guidelines for family and non-professional helpers on assisting an older person who is developing cognitive impairment or has dementia: a Delphi expert consensus study. AB - BACKGROUND: Assisting a person with dementia can lead to significant carer burden and possible negative outcomes for the person. Using the Delphi method, this study developed expert consensus guidelines for how family and non-professional carers should assist a person who is developing cognitive impairment, or has dementia or delirium. METHODS: A systematic search of websites, books and journal articles was conducted to develop a questionnaire containing items about the knowledge, skills and actions needed for assisting a person who is developing cognitive impairment, or has dementia or delirium. These items were rated over three rounds by two international expert panels comprising professionals specialising in research or treatment of dementia, and dementia carer advocates. RESULTS: A total of 65 participants (43 in the professional panel and 22 in the carer advocate panel) completed all three survey rounds. Of the 656 survey items that were rated, a total of 389 items were endorsed by at least 80 % of each panel. The endorsed items formed the basis of a guidelines document that explains what family and non-professional carers need to know and do when assisting a person who is developing cognitive impairment, or has dementia or delirium. CONCLUSIONS: The two groups of experts were able to reach substantial consensus on how to assist a person who is developing cognitive impairment, or has dementia or delirium. PMID- 27387757 TI - Optimal staging system for predicting the prognosis of patients with hepatocellular carcinoma in China: a retrospective study. AB - BACKGROUND: Several staging systems have been developed to evaluate patients with hepatocellular carcinoma (HCC), including the China Staging System (CS), the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, and seventh edition; the Barcelona Clinic Liver Cancer (BCLC) staging system, and Cancer of the Liver Italian Program (CLIP) staging system. The optimal staging system for to evaluate patients in China with HCC has not been determined. This study was designed to determine the optimal staging system for predicting patient prognosis by comparing the performances of these four staging systems in a cohort of Chinese patients with HCC. METHODS: This study enrolled 307 consecutive Chinese patients with HCC in Shandong Province. The performances of the CS, TNM, BCLC, and CLIP staging systems were compared and ranked using a concordance index. Predictors of survival were identified using univariate and multivariate Cox model analyses. RESULTS: The mean overall survival of the patient cohort was 12.08 +/- 11.87 months. Independent predictors of survival included tumor size, number of lesions, tumor thromboses, cirrhosis, serum albumin level and serum total bilirubin level. Compared with the other three staging systems, the CS staging system showed optimal performance as an independent predictor of patient survival. The BCLC staging system showed the poorest performance; its treatment algorithm was not suitable for patients in this study. CONCLUSIONS: CS was the most suitable staging system for predicting survival of patients with HCC in China. PMID- 27387758 TI - Early changes in the metabolic profile of activated CD8(+) T cells. AB - BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes. RESULTS: We found that proliferation inducing conditions result in an increase in key glycolytic metabolites, whereas the citric acid cycle remains unaffected. The upregulation of glycolysis led to a strong lactate production, which depends upon AKT/PKB, but not mTOR. The observed upregulation of lactate dehydrogenase results in increased lactate production, which we found to be dependent on IL-2 and to be required for proliferation. Additionally we observed upregulation of Glucose-transporter 1 (GLUT1) and glucose uptake upon stimulation, which were surprisingly not influenced by AKT inhibition. CONCLUSIONS: Our findings suggest that AKT plays a central role in upregulating glycolysis via induction of lactate dehydrogenase expression, but has no impact on glucose uptake of T cells. Furthermore, under apoptosis inducing conditions, T cells are not able to upregulate glycolysis and induce lactate production. In addition maintaining high glycolytic rates strongly depends on IL-2 production. PMID- 27387759 TI - The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial. AB - BACKGROUND: Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. QUESTIONS/PURPOSES: (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? METHODS: Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. RESULTS: Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). CONCLUSIONS: This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. LEVEL OF EVIDENCE: Level I, therapeutic study. PMID- 27387760 TI - Editor's Spotlight/Take 5: CORR(r) ORS Richard A. Brand Award: Clinical Trials of a New Treatment Method for Adhesive Capsulitis. PMID- 27387761 TI - Circulating tumor cells in the blood of poorly differentiated nasal squamous cell carcinoma patients: correlation with treatment response. AB - CONCLUSION: The results implied that CTCs were common even in early TNM stages and might become a potential parameter in evaluating therapeutic effects of radio and chemotherapies. BACKGROUND: Nasopharyngeal carcinoma (NPC) is a head and neck malignancy with an extraordinary high incidence in Southern China and a high metastasis rate. Analysis of circulating tumor cells (CTCs) in peripheral blood is a relatively new prognostic marker for cancer patients. PATIENTS AND METHODS: This retrospective study included data from 38 nasopharyngeal patients with poorly differentiated squamous cell carcinoma in TNM stage I (n = 2), TNM stage II (n = 12), TNM stage III (n = 8), and TNM stage IV (n = 16). CTCs in peripheral blood of all patients were counted before and 1 week as well as 1 months after radiotherapy. RESULTS: The data showed that in 52.6% of the patients CTCs could be detected in peripheral blood and the numbers were significantly decreased 1 month after radiotherapy treatment (p < 0.001). There was no correlation between CTC number or positivity and TNM stages or other clinical parameters. PMID- 27387762 TI - Solvent-Dependent Self-Assembly of an Oxalato-Based Three-Dimensional Magnet Exhibiting a Novel Architecture. AB - The old but evergreen family of bimetallic oxalates still offers innovative and interesting results. When (Me4N)3[Cr(ox)3].3H2O is reacted with Mn(II) ions in a nonaqueous solvent, a novel three-dimensional magnet of the formula [N(CH3)4]6[Mn3Cr4(ox)12].6CH3OH is obtained instead of the one-dimensional compound obtained in water. This new material exhibits an unprecedented stoichiometry with a binodal (3,4) net topology and the highest critical temperature (TC = 7 K) observed so far in a manganese-chromium oxalate based magnet. PMID- 27387763 TI - Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage. AB - Lineage-specific transcription factors determine the cell fate during development. Direct conversion of several cell types into other lineages has been achieved by the overexpression of specific transcription factors. Even cancer cells have been demonstrated to be amenable to transdifferentiation. Here, we identified a distinct set of transcription factors, which are sufficient to transform cells of the keratinocytic lineage to melanocyte-like cells. Melanocyte marker expression was induced and melanosome formation was observed in non tumorigenic keratinocytes (HaCaT) and tumorigenic squamous cell carcinoma (MET-4) cells. Moreover, reduced proliferation, cell metabolism, invasion and migration were measured in vitro in transdifferentiated MT-MET-4 cells. A loss of tumorigenic potential of squamous cell carcinoma cells could be due to the upregulation of the melanocyte differentiation associated gene IL-24. Our data show that cells from the keratinocytic lineage can be transdifferented into the melanocytic lineage and provide a proof of principle for a potential new therapeutic strategy. PMID- 27387764 TI - Breathlessness and inflammation: potential relationships and implications. AB - PURPOSE OF REVIEW: Breathlessness and chronic inflammation both span a wide range of disease contexts and hold prognostic significance. The possibility of a causal relationship between the two has been hypothesized. The aims of this article are to review the intersections between breathlessness and inflammation in the literature, describe potential mechanisms connecting the two phenomena, and discuss the potential clinical implications of a causal relationship. RECENT FINDINGS: There is a very limited literature exploring the relationship between systemic inflammation and breathlessness in chronic obstructive pulmonary disease, heart failure, and cancer. One large study in cancer patients is suggestive of a weak association between self-reported breathlessness and inflammation. Studies exploring the relationship between inflammation and Medical Research Council Dyspnoea grade in chronic obstructive pulmonary disease patients have produced inconsistent findings. Although a causal relationship has not yet been proven, there is evidence to support the existence of potential mechanisms mediating a relationship. This evidence points to a role for the skeletal muscle and stress hormone systems. SUMMARY: There is much progress to be made in this area. Interventional studies, evaluating the impact of anti-inflammatory interventions on breathlessness, are needed to help determine whether a causal relationship exists. If proven, this relationship might have important implications for both the treatment and impact of breathlessness. PMID- 27387765 TI - Whose value is it anyway? Clinical ethics in palliative and supportive care. PMID- 27387766 TI - Iron Supplementation for Chemotherapy-Induced Anemia in Patients Receiving Erythropoiesis-Stimulating Agents. AB - Clinical Question: What are the benefits and harms of iron supplementation alone and as an adjunct to erythropoiesis-stimulating agents (ESAs) compared with ESA alone in the treatment of chemotherapy-induced anemia? Bottom Line: Addition of iron to ESAs improves hematopoietic response, reduces the need for red blood cell transfusions, increases hemoglobin levels, and seems to be well tolerated. The subgroup analyses suggest the superiority of parenteral iron over oral iron supplementation in the treatment of chemotherapy-induced anemia. PMID- 27387768 TI - Protective role of biliverdin against bile acid-induced oxidative stress in liver cells. AB - The accumulation of bile acids affects mitochondria causing oxidative stress. Antioxidant defense is accepted to include biotransformation of biliverdin (BV) into bilirubin (BR) through BV reductase alpha (BVRalpha). The mutation (c.214C>A) in BLVRA results in a non-functional enzyme (mutBVRalpha). Consequently, homozygous carriers suffering from cholestasis develop green jaundice. Whether BVRalpha deficiency reduces BV-dependent protection against bile acids is a relevant question because a screening of the mut-BLVRA allele (a) in 311 individuals in Greenland revealed that this SNP was relatively frequent in the Inuit population studied (1% a/a and 4.5% A/a). In three human liver cell lines an inverse correlation between BVRalpha expression (HepG2>Alexander>HuH-7) and basal reactive oxygen species (ROS) levels was found, however the ability of BV to reduce oxidative stress and cell death induced by deoxycholic acid (DCA) or potassium dichromate (PDC) was similar in these cells. The transduction of BVRalpha or mutBVRalpha in human placenta JAr cells with negligible BVRalpha expression or the silencing of endogenous BVRalpha expression in liver cells had no effect on DCA-induced oxidative stress and cell death or BV-mediated cytoprotection. DCA stimulated both superoxide anion and hydrogen peroxide production, whereas BV only inhibited the latter. DCA and other dihydroxy-bile acids, but not PDC, induced up-regulation of both BVRalpha and heme oxygenase-1 (HO-1) in liver cells through a FXR independent and BV insensitive mechanism. In conclusion, BV exerts direct and BVRalpha-independent antioxidant and cytoprotective effects, whereas bile acid accumulation in cholestasis stimulates the expression of enzymes favoring the heme biotransformation into BV and BR. PMID- 27387770 TI - Genetically encoded probes for NAD+/NADH monitoring. AB - NAD+ and NADH participate in many metabolic reactions. The NAD+/NADH ratio is an important parameter reflecting the general metabolic and redox state of different types of cells. For a long time, in situ and in vivo NAD+/NADH monitoring has been hampered by the lack of suitable tools. The recent development of genetically encoded indicators based on fluorescent proteins linked to specific nucleotide-binding domains has already helped to address this monitoring problem. In this review, we will focus on four available indicators: Peredox, Frex family probes, RexYFP and SoNar. Each indicator has advantages and limitations. We will also discuss the most important points that should be considered when selecting a suitable indicator for certain experimental conditions. PMID- 27387769 TI - Melatonin prevents adverse myocardial infarction remodeling via Notch1/Mfn2 pathway. AB - Mitochondrial dysfunction is linked with myocardial infarction (MI), a disorder in which Notch1 has attracted increasing attention. However, the involvement of Notch1 in mitochondrial impairment after an MI is poorly understood, as is the role of mitochondrial fusion-associated protein 2 (Mfn2). Moreover, whether melatonin potentiates the Notch1/Mfn2 pathway in post-MI cardiac damage remains unclear. In our study, small interfering RNAs against Notch1 or Mfn2 and Jagged1 peptide were delivered via intramyocardial injection. At 3 days after these treatments, MI was induced by ligation of the anterior descending branch. We found that this ablation of Notch1 or Mfn2 aggravated post-MI injury, including worsened mitochondrial damage and increased generation of reactive oxygen species (ROS). In contrast, Jagged1 improved mitochondrial structure and function, decreased ROS production and attenuated post-MI injury. Interestingly, though Mfn2 expression was mildly regulated by Notch1 signaling in myocardium, Mfn2 deficiency nearly eliminated the cardioprotection by Jagged1, as evidenced by suppressed cardiac function, aggravated myocardial fibrosis, increased cell apoptosis, worsened mitochondrial impairment and enhanced oxidative stress. These observations revealed that Mfn2 plays an indispensable role in protection against MI-induced injury by Notch1. The mechanism might involve disrupting a damaging cycle of mitochondrial damage and ROS generation. Furthermore, melatonin activated Notch1 signaling and increased Mfn2 expression were reversed by luzindole, a nonselective antagonist of the melatonin receptor. Notably, melatonin attenuated post-MI injury in normal mice, but not in mice deficient in Notch1 or Mfn2. These results demonstrate that melatonin attenuates post-MI injury via the Notch1/Mfn2 pathway in a receptor-dependent manner. PMID- 27387767 TI - Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders. AB - The Mitochondrial Lon protease, also called LonP1 is a product of the nuclear gene LONP1. Lon is a major regulator of mitochondrial metabolism and response to free radical damage, as well as an essential factor for the maintenance and repair of mitochondrial DNA. Lon is an ATP-stimulated protease that cycles between being bound (at the inner surface of the inner mitochondrial membrane) to the mitochondrial genome, and being released into the mitochondrial matrix where it can degrade matrix proteins. At least three different roles or functions have been ascribed to Lon: 1) Proteolytic digestion of oxidized proteins and the turnover of specific essential mitochondrial enzymes such as aconitase, TFAM, and StAR; 2) Mitochondrial (mt)DNA-binding protein, involved in mtDNA replication and mitogenesis; and 3) Protein chaperone, interacting with the Hsp60-mtHsp70 complex. LONP1 orthologs have been studied in bacteria, yeast, flies, worms, and mammals, evincing the widespread importance of the gene, as well as its remarkable evolutionary conservation. In recent years, we have witnessed a significant increase in knowledge regarding Lon's involvement in physiological functions, as well as in an expanding array of human disorders, including cancer, neurodegeneration, heart disease, and stroke. In addition, Lon appears to have a significant role in the aging process. A number of mitochondrial diseases have now been identified whose mechanisms involve various degrees of Lon dysfunction. In this paper we review current knowledge of Lon's function, under normal conditions, and we propose a new classification of human diseases characterized by a either over-expression or decline or loss of function of Lon. Lon has also been implicated in human aging, and we review the data currently available as well as speculating about possible interactions of aging and disease. Finally, we also discuss Lon as potential therapeutic target in human disease. PMID- 27387771 TI - Intracellular labile iron determines H2O2-induced apoptotic signaling via sustained activation of ASK1/JNK-p38 axis. AB - Hydrogen peroxide (H2O2) acts as a second messenger in signal transduction participating in several redox regulated pathways, including cytokine and growth factor stimulated signals. However, the exact molecular mechanisms underlying these processes remain poorly understood and require further investigation. In this work, using Jurkat T lymphoma cells and primary human umbilical vein endothelial cells, it was observed that changes in intracellular "labile iron" were able to modulate signal transduction in H2O2-induced apoptosis. Chelation of intracellular labile iron by desferrioxamine rendered cells resistant to H2O2 induced apoptosis. In order to identify the exact points of iron action, we investigated selected steps in H2O2-mediated apoptotic pathway, focusing on mitogen activated protein kinases (MAPKs) JNK, p38 and ERK. It was observed that spatiotemporal changes in intracellular labile iron, induced by H2O2, influenced the oxidation pattern of the upstream MAP3K ASK1 and promoted the sustained activation of JNK-p38 axis in a defined time-dependent context. Moreover, we indicate that H2O2 induced spatiotemporal changes in intracellular labile iron, at least in part, by triggering the destabilization of lysosomal compartments, promoting a concomitant early response in proteins of iron homeostasis. These results raise the possibility that iron-mediated oxidation of distinct proteins may be implicated in redox signaling processes. Since labile iron can be pharmacologically modified in vivo, it may represent a promising target for therapeutic interventions in related pathological conditions. PMID- 27387772 TI - Processing speed is associated with differences in IQ and cognitive profiles between patients with schizophrenia and their healthy siblings. AB - BACKGROUND: Processing speed turns out to be the central area of research on cognition in schizophrenia. So far the relationship between this dimension and the IQ level of patients and their healthy siblings has not been investigated. AIM: To investigate the differences in cognitive speed in patients with schizophrenia and their healthy siblings, and to determine whether cognitive speed as a covariate affects differences in IQ and cognitive profiles between groups. METHODS: Forty-seven inpatients diagnosed with schizophrenia according to DSM-IV (SCH) and their 36 healthy siblings (HSB) were tested with cognitive speed tasks according to Bartzokis et al. method and Wechsler Intelligence Scale. Additional control for the possible impact of antipsychotic drugs and selected demographic variables on the cognitive performance was taken into account. RESULTS: The siblings scored significantly higher in the cognitive speed task (p < 0.01) than patients, the WAIS-R cognitive test profiles were also significantly different in two ways: between groups, and between single test results in each of the assessed groups. The interaction effect: ANOVA, F(10, 770) = 2.798, p = 0.002. Similarly, the Performance and Full Scale IQs were significantly different, at p < 0.01. After controlling for cognitive speed, all significant differences no longer exist: e.g. Full Scale IQ, p = 0.459. CONCLUSIONS: Significant differences in cognitive speed between patients and their healthy siblings generate the differences in the cognitive profile assessed with Wechsler Intelligence Scale. Some problems of cognitive speed diagnosis and further research on the cognitive schizophrenia endophenotype were discussed. PMID- 27387773 TI - Hierarchically porous bio-inspired films prepared by combining "breath figure" templating and selectively degradable block copolymer directed self-assembly. AB - Polymer films with hierarchical micro- and nano-porosities were prepared by combining the fast solvent evaporation "Breath Figure" (BF) method, exhibiting a highly regular honeycomb micro-porous texture, with the additional nanoscale self assembly of polylactide-block-polystyrene (PLA-b-PS) diblock copolymers, PLA being used thereafter as a sacrificial component for nano-porosity. PMID- 27387774 TI - Getting to "Zero" on Central-Line Infections in the PICU. PMID- 27387775 TI - Intensivist-Driven Ultrasound in the PICU: Can Pediatric Intensivists Decipher the Heart's Mysteries? PMID- 27387776 TI - Improving Outcomes of Critically Ill Children With Simulation-Based Education: Where Are We Now in the Year 2016? PMID- 27387777 TI - Acute Kidney Injury Has a Long-Term Impact on Survival After Stage 1 Palliation of Univentricular Hearts-It's Not Just Just One and Done. PMID- 27387778 TI - Early Extubation: Unintended Consequences and Missed Opportunities? PMID- 27387779 TI - Supporting Families After Traumatic Brain Injury, Is This a Way of Improving Results? PMID- 27387780 TI - Well-"Rounded" Medical Teams-What Does It Take? PMID- 27387781 TI - Caring for the Team Is Caring for the Patient (and the Future). PMID- 27387782 TI - Severe Hyperbilirubinemia in Exchange Transfusion: Less Indication and Lower Mortality. PMID- 27387783 TI - The authors reply. PMID- 27387784 TI - About Intracranial Hypertension in Pediatric Patients: Good News About Treatment...But What About the Role of Optic Nerve Sheath Diameter Measurement in the Diagnosis? PMID- 27387785 TI - The authors reply. PMID- 27387786 TI - Effect of Ondansetron on QT Interval in Patients Cared for in the PICU. AB - OBJECTIVES: There is no evidence regarding the effect of ondansetron on the QT interval in pediatric patients in the ICU. This study aimed to describe the effect of ondansetron on the corrected QT interval in patients cared for in the PICU. DESIGN: Retrospective cohort, consecutive enrollment study. SETTING: Single center, tertiary-level, medical/surgical PICU. PATIENTS: All patients less than 8 years old who received ondansetron over an 11-month period were included. Exclusion criteria were atrial arrhythmia, bundle-branch block, known congenital long QT syndrome, and concomitant administration of proarrhythmic antiarrhythmic agents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 210 doses of ondansetron were administered to 107 patients, with a mean age 10.5 +/- 4.8 years; 49% were men. Corrected QT interval increased to 460-500 ms in 29% and to more than 500 ms in 11% of events of ondansetron administration. The mean baseline corrected QT interval even before ondansetron administration was higher for these groups (460-500 and > 500 ms; 457 +/- 33 and 469 +/- 45, respectively; p <= 0.05). In multivariate analysis, both groups were associated significantly with underlying electrolyte abnormalities (odds ratio, 2.2; 95% CI, 1.1-4.4 and odds ratio, 5.1; 95% CI, 1.8-15.7, respectively); the group with corrected QT interval more than 500 ms was also significantly associated with organ dysfunction (odds ratio, 3.2; 95% CI, 1.1-9.4). As the numbers of risk factors increased from only ondansetron to three additional QT aggravating factors (electrolyte abnormalities, administration of other QT-prolonging drugs, and organ dysfunction), the likelihood of being associated with corrected QT interval more than 500 ms increased. CONCLUSIONS: Prolonged QT interval is observed commonly in PICUs following the administration of ondansetron. Underlying risk factors, such as electrolyte abnormalities and organ dysfunction, seem to pose the highest risk of prolongation of QT interval in these patients. The awareness of prevalent risk factors for increased corrected QT interval may help identify patients at high risk for arrhythmias. PMID- 27387787 TI - Direct Atomic-Orbital-Based Relativistic Two-Component Linear Response Method for Calculating Excited-State Fine Structures. AB - In this work, we present a linear-response formalism of the complex two-component Hartree-Fock Hamiltonian that includes relativistic effects within the Douglas Kroll-Hess and the Exact-Two-Component frameworks. The method includes both scalar and spin relativistic effects in the variational description of electronic ground and excited states, although it neglects the picture-change and explicit spin-orbit contributions arising from the two-electron interaction. An efficient direct formalism of solving the complex two-component response function is also presented in this work. The presence of spin-orbit couplings in the Hamiltonian and the two-component nature of the wave function and Fock operator allows the computation of excited-state zero-field splittings of systems for which relativistic effects are dominated by the one-electron term. Calculated results are compared to experimental reference values to assess the quality of the underlying approximations. The results show that the relativistic two-component linear response methods are able to capture the excited-state zero-field splittings with good agreement with experiments for the systems considered here, with all approximations exhibiting a similar performance. However, the error increases for heavy elements and for states of high orbital angular momentum, suggesting the importance of the two-electron relativistic effect in such situations. PMID- 27387788 TI - Structure and Mass Transport Characteristics at the Intrinsic Liquid-Vapor Interfaces of Alkanes. AB - In this paper, an instantaneous interface definition has been used to study the intrinsic structure and self-diffusion coefficient in the vicinity of the liquid vapor interfaces of decane and tetracosane at three different temperatures using molecular dynamics simulations, and the results have been compared with those obtained on the basis of the conventional Gibbs dividing surface (time- and space averaged interface). The alkane molecules were modeled using the united atom NERD force field. Partial layered structures of alkane molecules at the liquid-vapor interface are observed as a pinned structure of alkane liquids based on the intrinsic interface. This kind of characteristic has not been observed in the density profiles obtained based on the Gibbs dividing surface. By examining the orientation order parameter and radius of gyration of the alkane molecules, it was observed that the alkane molecules were preferentially oriented to be more parallel to the intrinsic interface than to the Gibbs dividing surface, and the shape of the alkane molecules is slightly changed in the vicinity of the liquid vapor interfaces. The self-diffusion coefficient parallel to the intrinsic interface was examined using the Green-Kubo relation, where the projection of the velocity in the parallel direction to the local intrinsic interface is used in the velocity correlation function. It was found that the self-diffusion coefficient in the direction parallel to the intrinsic interface changes as the position approaches the interface in a more obvious manner as compared with the self-diffusion coefficient obtained with respect to the Gibbs dividing surface. These results suggest that the use of an instantaneous interface definition allowed us to capture sharp variations in transport properties which are originating due to steeper structure at the liquid-vapor interfaces. PMID- 27387789 TI - Probing Ion Transfer across Liquid-Liquid Interfaces by Monitoring Collisions of Single Femtoliter Oil Droplets on Ultramicroelectrodes. AB - We describe a method of observing collisions of single femtoliter (fL) oil (i.e., toluene) droplets that are dispersed in water on an ultramicroelectrode (UME) to probe the ion transfer across the oil/water interface. The oil-in-water emulsion was stabilized by an ionic liquid, in which the oil droplet trapped a highly hydrophobic redox probe, rubrene. The ionic liquid also functions as the supporting electrolyte in toluene. When the potential of the UME was biased such that rubrene oxidation would be possible when a droplet collided with the electrode, no current spikes were observed. This implies that the rubrene radical cation is not hydrophilic enough to transfer into the aqueous phase. We show that current spikes are observed when tetrabutylammonium trifluoromethanesulfonate or tetrahexylammonium hexafluorophosphate are introduced into the toluene phase and when tetrabutylammonium perchlorate is introduced into the water phase, implying that the ion transfer facilitates electron transfer in the droplet collisions. The current (i)-time (t) behavior was evaluated quantitatively, which indicated the ion transfer is fast and reversible. Furthermore, the size of these emulsion droplets can also be calculated from the electrochemical collision. We further investigated the potential dependence on the electrochemical collision response in the presence of tetrabutylammonium trifluoromethanesulfonate in toluene to obtain the formal ion transfer potential of tetrabutylammonium across the toluene/water interface, which was determined to be 0.754 V in the inner potential scale. The results yield new physical insights into the charge balance mechanism in emulsion droplet collisions and indicate that the electrochemical collision technique can be used to probe formal ion transfer potentials between water and solvents with very low (epsilon < 5) dielectric constants. PMID- 27387790 TI - Natural history of medial clavicle fractures. AB - BACKGROUND: Fractures of the medial third of the clavicle comprise less than 3% of all clavicle fractures. The natural history and optimal management of these rare injuries are unknown. The aim of our study is to describe the demographics, management and outcomes of patients with medial clavicle fractures treated at a Level 1 Trauma Centre. METHODS: A retrospective review was conducted of patients presenting to our institution between January 2008 and March 2013 with a medial third clavicle fracture. Clinical and radiographic data were recorded including mechanism of injury, fracture pattern and displacement, associated injuries, management and complications. Functional outcomes were assessed using the Glasgow Outcome Scale Extended (GOS-E) scores from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Shoulder outcomes were assessed using two patient reported outcomes scores, the American Shoulder and Elbow Society Score (ASES) and the Subjective Shoulder Value (SSV). RESULTS: Sixty eight medial clavicle fractures in 68 patients were evaluated. The majority of patients were male (n=53), with a median age of 53.5 years (interquartile range (IQR) 37.5-74.5 years). The most common mechanism of injury was motor vehicle accident (n=28). The in-hospital mortality rate was 4.4%. The fracture pattern was almost equally distributed between extra articular (n=35) and intra-articular (n=33). Fifty-five fractures (80.9%) had minimal or no displacement. Associated injuries were predominantly thoracic (n=31). All fractures were initially managed non operatively, with a broad arm sling. Delayed operative fixation was performed for painful atrophic delayed union in two patients (2.9%). Both patients were under 65 years of age and had a severely displaced fracture of the medial clavicle. One intra-operative vascular complication was seen, with no adverse long-term outcome. Follow-up was obtained in 85.0% of the surviving cohort at an average of three years post injury (range 1-6 years). The mean ASES score was 80.3 (SD 24.8, range 10-100,), and the mean SSV score was 77.0 (SD 24.6, range 10-100). CONCLUSION: Sixty eight patients with medial clavicle fractures were identified over a 5year period, with excellent functional results seen following conservative management. PMID- 27387791 TI - Temporal bone fracture: Evaluation in the era of modern computed tomography. AB - BACKGROUND: Temporal bone fractures (TBFs) are harbingers of high energy head trauma that can result in a variety of significant complications of the auditory, vestibular, nervous, and vascular systems. Multiple cohort studies have identified the incidence and proper evaluation of these fractures. We hypothesize that these have changed with the advent of modern high resolution computer tomography (CT) imaging. METHODS: We performed a retrospective review of all TBFs admitted to an urban level one trauma center between June 1, 2011 and May 31, 2015. A database was compiled including demographics, physical exam findings, imaging performed and results, morphology and directionality of fracture as well as outcomes and follow-up. RESULTS: One hundred thirteen patients were identified, representing 4.7% of skull fractures and 35.9% of skull base fractures. Most were subsequent to falls (41.6%) followed by pedestrian vehicular trauma (19.5%). The majority of TBF patients (67.3%) had additional fractures of the skull and 77.9% of TBF patients also had some kind of intracranial hemorrhage. The morphology of TBF and the overall mortality (7.9%) was consistent with previous reports. The incidence of facial nerve paralysis (1.6%), CSF leak (1.7%), and hearing loss (18.6%) were all lower than previously reported. Trauma imaging was able to identify 98.6% of TBF, calling the utility of routine temporal bone CT imaging into question. CONCLUSION: TBFs are less common than they once were and though they still carry a mortality rate similar to previously reported cohorts, the incidence of complications among survivors has dramatically improved. Additionally, modern CT imaging is very capable of identifying these injuries and dedicated temporal bone CT may only be of utility in cases where facial nerve injury or vascular injury is suspected. LEVEL OF EVIDENCE: Epidemiologic study, Level III. PMID- 27387792 TI - Laser Ablation Synthesis of Gold Selenides by using a Mass Spectrometer as a Synthesizer: Laser Desorption Ionization Time-of-Flight Mass Spectrometry. AB - Methods for the rapid construction of new chemical motifs have the potential to accelerate the development of nanoscience. The synthesis of new chemical entities by laser ablation has been systematically demonstrated by using mixtures of gold and selenium. The compounds generated are detected by time-of-flight mass spectrometry and, for selected compounds, the structure is investigated by using density functional theory optimization. In total, 67 new gold selenide clusters have been synthesized, demonstrating an unsuspected richness in gold chemistry. Chemical species generated in the gas phase might inspire new routes for the synthesis of novel compounds in the solid state. PMID- 27387793 TI - The Importance of Amoxicillin and Amoxicillin-Clavulanate Determinants in the Diagnosis of Immediate Allergic Reactions to beta-Lactams. AB - BACKGROUND: Immediate allergic reactions to beta-lactam antibiotics are considered to be one of the most important drug hypersensitivities. A positive skin test (ST) with a combination of major and minor penicillin determinants is usually sufficient to recommend avoidance of the culprit drug, whereas a negative ST is usually followed by an oral challenge test (OCT). Recently, concern has been raised regarding the role of amoxicillin (AMX) ST in the diagnosis of AMX allergy. OBJECTIVE: The aim of this study was to examine the additive value of AMX determinants in STs of patients with immediate hypersensitivity reactions to AMX or AMX-clavulanate (AMX-C). METHODS: Patients with a history of immediate AMX or AMX-C allergy underwent an ST using a combination of penicilloyl-polylysine (PPL) and minor determinants as well as AMX. An ST with AMX-C was added when appropriate. RESULTS: Thirty-one patients were evaluated. Eight patients, all of them with a history of AMX allergy, had positive reactions only to the AMX component. Two patients with AMX-C allergy had a positive ST reaction only to the AMX-C component. Moreover, only 14 patients (13 with AMX and 1 with AMX-C allergy) had a positive reaction to PPL, whereas most patients (54.8%) had positive reactions to other determinants. One patient, who was positive for AMX, developed several urticarial lesions after the test. CONCLUSIONS: Skin testing with AMX and AMX-C is mandatory in patients with immediate allergy to these drugs. Failure to perform it may result in a false-negative ST jeopardizing these patients with anaphylactic reactions during a hazardous OCT. PMID- 27387794 TI - Flipping the Switch "On" for Aminoglycoside-Resistance Enzymes: The Mechanism Is Finally Revealed! AB - In a recent issue of Structure, Caldwell et al. (2016) determined crystal structures of APH(2")-Ia in complex with various combinations of aminoglycosides and nucleosides, which compellingly revealed that the catalytic activity of this resistance enzyme is regulated by a conformational change of the triphosphate of GTP, a mechanism previously unknown for antibiotic kinases. PMID- 27387795 TI - Temporal-spatial variation and partitioning prediction of antibiotics in surface water and sediments from the intertidal zones of the Yellow River Delta, China. AB - As special zones, the intertidal zones of the Yellow River Delta (YRD) are highly variable along with time and space. Fluvial-marine and land-ocean interactions which frequently occur in these areas have a great impact on the fate of pollutants. Antibiotics, which contribute to antibiotic-resistant genes (ARGs), are widely detected in wastewater, natural water, soil, sediments, and even drinking water. Therefore, it is meaningful to investigate the occurrence and fate of antibiotics in these special zones. In this study, eight antibiotics belonging to tetracyclines (TCs), fluoroquinolones (FQs), and macrolides (MLs) were detected in the surface water and sediments from the intertidal zones of YRD during two seasons. Two models were established to predict the partitioning coefficients of norfloxacin (NOR) and erythromycin (ETM) using physicochemical properties of sediments, respectively. The total concentrations of these antibiotics were 82.94-230.96ng.L(-1) and 40.97-207.44ng.g(-1), respectively, in the surface water and sediments. Seasonal variation was mainly influenced by the frequency of antibiotics use and environment factors. The regions with river supply exhibited the highest concentrations of antibiotics in surface water and sediments. Meanwhile, particle-size fractions, cation exchange capability (CEC), and metal ions content played dominant roles in the partitioning behaviors of NOR and ETM between the surface water and sediments. Both models established in this study featured accuracy and feasibility, which provided the methods for predicting the partitioning coefficients of emerging contaminants similar in structures to NOR and ETM in the intertidal zones. PMID- 27387796 TI - Western Lake Erie Basin: Soft-data-constrained, NHDPlus resolution watershed modeling and exploration of applicable conservation scenarios. AB - Complex watershed simulation models are powerful tools that can help scientists and policy-makers address challenging topics, such as land use management and water security. In the Western Lake Erie Basin (WLEB), complex hydrological models have been applied at various scales to help describe relationships between land use and water, nutrient, and sediment dynamics. This manuscript evaluated the capacity of the current Soil and Water Assessment Tool (SWAT) to predict hydrological and water quality processes within WLEB at the finest resolution watershed boundary unit (NHDPlus) along with the current conditions and conservation scenarios. The process based SWAT model was capable of the fine scale computation and complex routing used in this project, as indicated by measured data at five gaging stations. The level of detail required for fine scale spatial simulation made the use of both hard and soft data necessary in model calibration, alongside other model adaptations. Limitations to the model's predictive capacity were due to a paucity of data in the region at the NHDPlus scale rather than due to SWAT functionality. Results of treatment scenarios demonstrate variable effects of structural practices and nutrient management on sediment and nutrient loss dynamics. Targeting treatment to acres with critical outstanding conservation needs provides the largest return on investment in terms of nutrient loss reduction per dollar spent, relative to treating acres with lower inherent nutrient loss vulnerabilities. Importantly, this research raises considerations about use of models to guide land management decisions at very fine spatial scales. Decision makers using these results should be aware of data limitations that hinder fine-scale model interpretation. PMID- 27387797 TI - Organohalogen pollutants in surface particulates from workshop floors of four major e-waste recycling sites in China and implications for emission lists. AB - To examine the environmental pollution associated with e-waste recycling activities, the concentrations of organohologenated pollutants (OHPs), i.e., short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and several other halogenated flame retardants (OHFRs), were investigated in surface particulates from the workshop floors of four major e-waste recycling sites (Taizhou, Guiyu, Dali and Qingyuan) in China. The mean levels of SCCPs, MCCPs, PCBs, PBDEs and OHFRs in surface particulates ranged from 30,000-61,000, 170,000-890,000, 2700 27,000, 52,000-240,000, and 62,000-140,000ng/g dry weight (dw), respectively. OHFRs, including decabromodiphenyl ethane, dechlorane plus, 1,2-bis(2,4,6 tribromophenoxy)ethane, tetrabromobisphenol A, hexabromocyclododecanes, polybrominated biphenyls, hexabromobenzene, pentabromotoluene, and pentabromoethylbenzene, were frequently (>50% detection frequency) detected in surface particulates with mean concentration ranges of 39,000-63,000, 310-2700, 98-16,000, 21,000-56,000, 55-5700, 1700-27,000, 42-1600, 3.2-220, and 5.8-12ng/g dw, respectively. The composition of OHPs varied depend on the e-waste items processing in different regions. Guiyu and Dali were typical sites contaminated by halogenated flame retardants (HFRs) and CPs, respectively, while Qingyuan, and Taizhou were representative PCB-polluted regions. The evidence produced by this preliminary study indicated that electronic devices and plastics may account for the high content of HFRs and the metal products are likely the major source of CPs in these e-waste sites. PMID- 27387798 TI - Rate of exposure of a sentinel species, invasive American mink (Neovison vison) in Scotland, to anticoagulant rodenticides. AB - Anticoagulant rodenticides (ARs) are highly toxic compounds that are exclusively used for the control of rodent pests. Despite their defined use, they are nonetheless found in a large number of non-target species indicating widespread penetration of wildlife. Attempts to quantify the scale of problem are complicated by non-random sampling of individuals tested for AR contamination. The American mink (Neovison vison) is a wide ranging, non-native, generalist predator that is subject to wide scale control efforts in the UK. Exposure to eight ARs was determined in 99 mink trapped in NE Scotland, most of which were of known age. A high percentage (79%) of the animals had detectable residues of at least one AR, and more than 50% of the positive animals had two or more ARs. The most frequently detected compound was bromadiolone (75% of all animals tested), followed by difenacoum (53% of all mink), coumatetralyl (22%) and brodifacoum (9%). The probability of mink exposure to ARs increased by 4.5% per month of life, and was 1.7 times higher for mink caught in areas with a high, as opposed to a low, density of farms. The number of AR compounds acquired also increased with age and with farm density. No evidence was found for sexual differences in the concentration and number of ARs. The wide niche and dietary overlap of mink with several native carnivore species, and the fact that American mink are culled for conservation throughout Europe, suggest that this species may act as a sentinel species, and the application of these data to other native carnivores is discussed. PMID- 27387799 TI - Quantitative imaging of radial oxygen loss from Valisneria spiralis roots with a fluorescent planar optode. AB - Oxygen (O2) availability within the sediment-root interface is critical to the survival of macrophytes in O2-deficient sediment; however, our knowledge of the fine-scale impact of macrophyte roots upon the spatiotemporal dynamics of O2 is relatively limited. In this study, a non-invasive imaging technology was utilized to map O2 micro-distribution around Vallisneria spiralis. Long-term imaging results gathered during a 36day-period revealed an abundance of O2 spatiotemporal patterns ranging from 0 to 250MUmolL(-1). The root-induced O2 leakage and consequent oxygenated area were stronger in the vicinity of the basal root compared to that found in the root tip. The O2 images revealed V. spiralis exhibited radial O2 loss (ROL) along the entire root, and the O2 distribution along the root length showed a high degree of small-scale spatial heterogeneity decreasing from 80% at the basal root surface to 10% at the root tip. The oxygenated zone area around the roots increased as O2 levels increased with root growth and irradiance intensities ranging from 0 to 216MUmol photons m(-2)s(-1). A weak ROL measuring <20% air saturation around the basal root surface was maintained in darkness, which was presumably attributed to the O2 supply from overlying water via plant aerenchyma. The estimated total O2 release to the rhizosphere of V. spiralis was determined to range from 8.80+/-7.32 to 30.34+/ 17.71nmolm(-2)s(-1), which is much higher than many other macrophyte species. This O2 release may be an important contribution to the high-capacity of V. spiralis for quickly colonizing anaerobic sediment. PMID- 27387800 TI - Vegetation changes in recent large-scale ecological restoration projects and subsequent impact on water resources in China's Loess Plateau. AB - Recently, relationship between vegetation activity and temperature variability has received much attention in China. However, vegetation-induced changes in water resources through changing land surface energy balance (e.g. albedo), has not been well documented. This study investigates the underlying causes of vegetation change and subsequent impacts on runoff for the Northern Shaanxi Loess Plateau. Results show that satellite-derived vegetation index has experienced a significantly increasing trend during the past three decades, especially during 2000-2012. Large-scale ecological restorations, i.e., the Natural Forest Conservation project and the Grain for Green project, are found to be the primary driving factors for vegetation increase. The increased vegetation coverage induces decrease in surface albedo and results in an increase in temperature. This positive effect can be counteracted by higher evapotranspiration and the net effect is a decrease in daytime land surface temperature. A higher evapotranspiration rate from restored vegetation is the primary reason for the reduced runoff coefficient. Other factors including less heavy precipitation, increased water consumption from town, industry and agriculture also appear to be the important causes for the reduction of runoff. These two ecological restoration projects produce both positive and negative effects on the overall ecosystem services. Thus, long-term continuous monitoring is needed. PMID- 27387801 TI - Combining catchment modelling and sediment fingerprinting to assess sediment dynamics in a Spanish Pyrenean river system. PMID- 27387802 TI - Identification of groundwater microorganisms capable of assimilating RDX-derived nitrogen during in-situ bioremediation. AB - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a nitroamine explosive, is commonly detected in groundwater at military testing and training sites. The objective of this study was to characterize the microbial community capable of using nitrogen derived from the RDX or RDX intermediates during in situ bioremediation. Active groundwater microorganisms capable of utilizing nitro-, ring- or fully-labeled (15)N-RDX as a nitrogen source were identified using stable isotope probing (SIP) in groundwater microcosms prepared from two wells in an aquifer previously amended with cheese whey to promote RDX biodegradation. A total of fifteen 16S rRNA gene sequences, clustered in Clostridia, beta Proteobacteria, and Spirochaetes, were derived from the (15)N-labeled DNA fractions, suggesting the presence of metabolically active bacteria capable of using RDX and/or RDX intermediates as a nitrogen source. None of the derived sequences matched RDX-degrading cultures commonly studied in the laboratory, but some of these genera have previously been linked to RDX degradation in site groundwater via (13)C-SIP. When additional cheese whey was added to the groundwater samples, 28 sequences grouped into Bacteroidia, Bacilli, and alpha-, beta-, and gamma-Proteobacteria were identified. The data suggest that numerous bacteria are capable of incorporating N from ring- and nitro-groups in RDX during anaerobic bioremediation, and that some genera may be involved in both C and N incorporation from RDX. PMID- 27387803 TI - Glacial recharge, salinisation and anthropogenic contamination in the coastal aquifers of Recife (Brazil). AB - Implying large residence times and complex water origins deep coastal aquifers are of particular interest as they are remarkable markers of climate, water use and land use changes. Over the last decades, the Metropolitan Region of Recife (Brazil) went through extensive environmental changes increasing the pressure on water resources and giving rise to numerous environmental consequences on the coastal groundwater systems. We analysed the groundwater of the deep aquifers Cabo and Beberibe that are increasingly exploited. The processes potentially affecting groundwater residence times and flow paths have been studied using a multi-tracer approach (CFCs, SF6, noble gases, 14C, 2H and 18O). The main findings of these investigations show that: (1) Groundwaters of the Cabo and Beberibe aquifers have long residence times and were recharged about 20,000years ago. (2) Within these old groundwaters we can find palaeo-climate evidences from the last glacial period at the tropics with lower temperatures and dryer conditions than the present climate. (3) Recently, the natural slow dynamic of these groundwater systems was significantly affected by mixing processes with contaminated modern groundwater coming from the shallow unconfined Boa Viagem aquifer. (4) The large exploitation of these aquifers leads to a modification of the flow directions and causes the intrusion through palaeo-channels of saline water probably coming from the Capibaribe River and from the last transgression episodes. These observations indicate that the current exploitation of the Cabo and Beberibe aquifers is unsustainable regarding the long renewal times of these groundwater systems as well as their ongoing contamination and salinisation. The groundwater cycle being much slower than the human development rhythm, it is essential to integrate the magnitude and rapidity of anthropogenic impacts on this extremely slow cycle to the water management concepts. PMID- 27387804 TI - Maternal exposure to perfluoroalkyl acids measured in whole blood and birth outcomes in offspring. AB - Perfluoralkyl and polyfluoralkyl substances have been measured in plasma and serum of pregnant women as a measure of prenatal exposure. Increased concentrations of individual perfluoroalkyl acids (PFAAs), (typically perfluorooctanoic acid (PFOA) and perfluoroctane sulfonate (PFOS) have been reported to be associated with reductions in birth weight and other birth outcomes. We undertook a study of 14 PFAAs in whole blood (including PFOS, PFHxS, PFHpA, PFOA, PFNA, PFDA and PFUnDA) from 98 pregnant women in Western Australia from 2008 to 2011. Median concentrations (in MUg/L) were: PFOS 1.99; PFHxS 0.33; PFOA 0.86; PFNA 0.30; PFDA 0.12 and PFUnDA 0.08. Infants born to women with the highest tertile of PFHxS exposure had an increased odds of being <95% of their optimal birth weight (OR 3.5, 95% CI 1.1-11.5). Conversely, maternal blood concentrations of PFUnDA were associated with non-significant increases in average birth weight (+102g, 95% CI -41, 245) and significant increases in proportion of optimal birth weight (+4.7%, 95% CI 0.7, 8.8) per ln-unit change. This study has reported a range of PFAAs in the whole blood of pregnant women and suggests that PFHxS and PFUnDA may influence foetal growth and warrant further attention. Additional studies are required to identify the sources of PFAA exposure with a view to prevention, in addition to further studies investigating the long term health effects of these ubiquitous chemicals. PMID- 27387805 TI - River bank burrowing by invasive crayfish: Spatial distribution, biophysical controls and biogeomorphic significance. AB - Invasive species generate significant global environmental and economic costs and represent a particularly potent threat to freshwater systems. The biogeomorphic impacts of invasive aquatic and riparian species on river processes and landforms remain largely unquantified, but have the potential to generate significant sediment management issues within invaded catchments. Several species of invasive (non-native) crayfish are known to burrow into river banks and visual evidence of river bank damage is generating public concern and media attention. Despite this, there is a paucity of understanding of burrow distribution, biophysical controls and the potential significance of this problem beyond a small number of local studies at heavily impacted sites. This paper presents the first multi-catchment analysis of this phenomenon, combining existing data on biophysical river properties and invasive crayfish observations with purpose-designed field surveys across 103 river reaches to derive key trends. Crayfish burrows were observed on the majority of reaches, but burrowing tended to be patchy in spatial distribution, concentrated in a small proportion (<10%) of the length of rivers surveyed. Burrow distribution was better explained by local bank biophysical properties than by reach-scale properties, and burrowed banks were more likely to be characterised by cohesive bank material, steeper bank profiles with large areas of bare bank face, often on outer bend locations. Burrow excavation alone has delivered a considerable amount of sediment to invaded river systems in the surveyed sites (3tkm(-1) impacted bank) and this represents a minimum contribution and certainly an underestimate of the absolute yield (submerged burrows were not recorded). Furthermore, burrowing was associated with bank profiles that were either actively eroding or exposed to fluvial action and/or mass failure processes, providing the first quantitative evidence that invasive crayfish may cause or accelerate river bank instability and erosion in invaded catchments beyond the scale of individual burrows. PMID- 27387806 TI - Mathematical modeling based evaluation and simulation of boron removal in bioelectrochemical systems. AB - Boron removal is an arising issue in desalination plants due to boron's toxicity. As an emerging treatment concept, bioelectrochemical systems (BES) can achieve potentially cost-effective boron removal by taking advantage of cathodic-produced alkali. Prior studies have demonstrated successful removal of boron in microbial desalination cells (MDCs) and microbial fuel cells (MFCs), both of which are representative BES. Herein, mathematical models were developed to further evaluate boron removal by different BES and understand the key operating factors. The models delivered very good prediction of the boron concentration in the MDC integrated with Donnan Dialysis (DD) system with the lowest relative root-mean square error (RMSE) of 0.00%; the predication of the MFC performance generated the highest RMSE of 18.55%. The model results of salt concentration, solution pH, and current generation were well fitted with experimental data for RMSE values mostly below 10%. The long term simulation of the MDC-DD system suggests that the accumulation of salt in the catholyte/stripping solution could have a positive impact on the removal of boron due to osmosis-driven convection. The current generation in the MDC may have little influence on the boron removal, while in the MFC the current-driven electromigration can contribute up to 40% of boron removal. Osmosis-induced convection transport of boron could be the major driving force for boron removal to a low level <2mgL(-1). The ratio between the anolyte and the catholyte flow rates should be kept >22.2 in order to avoid boron accumulation in the anolyte effluent. PMID- 27387807 TI - The seasonal fluctuations and accumulation of iodine-129 in relation to the hydrogeochemistry of the Wolf Creek Research Basin, a discontinuous permafrost watershed. AB - The long lived radioisotope (129)I is a uranium fission product, and an environmental contaminant of the nuclear age. Consequently, it can trace anthropogenic releases of (129)I in watersheds, and has been identified as a potential means to distinguish water sources in discharge (Nimz, 1998). The purpose of this work was to identify the sources and mass input of (129)I and trace the transport, partitioning and mass balance of (129)I over time in a remote watershed. We monitored (129)I and other geochemical and isotope tracers (e.g. delta(14)CDIC, delta(13)CDIC, delta(2)H, delta(18)O, etc.) in precipitation and discharge from the Wolf Creek Research Basin (WCRB), a discontinuous permafrost watershed in the Yukon Territory, Canada, and evaluated the use of (129)I as a water end-member tracer. Radiocarbon and geochemical tracers of weathering show that discharge is comprised of (i) groundwater baseflow that has recharged under open system conditions, (ii) spring freshet meltwater that has derived solutes through closed-system interaction with saturated soils, and (iii) active layer drainage. The abundance of (129)I and the (129)I/(127)I ratio correlated with geochemical tracers suggests varying contributions of these three water end-members to discharge. The (129)I concentration was highest at the onset of freshet, reaching 17.4*10(6) atoms/L, and likely reflects the lack of interaction between meltwater and organic matter at that time. This peak in (129)I was followed by a decline over the summer to its lowest value. Mass balance calculations of the (129)I budget show that the input to the watershed via precipitation is nearly one order of magnitude higher than the output suggesting that such arctic watersheds accumulate nearly 90% of the annual input, primarily in soil organic matter. Temporal variations in discharge (129)I concentrations correlated with changes in discharge water sources suggesting that (129)I is a promising hydrologic tracer, particularly when used in concert with other stable and radioisotopes. PMID- 27387808 TI - Spatiotemporal variation of ozone precursors and ozone formation in Hong Kong: Grid field measurement and modelling study. AB - Grid field measurements of volatile organic compounds (VOCs) covering the entire territory of Hong Kong were simultaneously carried out twice daily on 27 September 2013 and 24 September 2014, respectively, to advance our understanding on the spatiotemporal variations of VOCs and ozone (O3) formation, the factors controlling O3 formation and the efficacy of a control measure in Hong Kong. From before to after the control measure on liquefied petroleum gas (LPG) fueled vehicles, the VOCs originated from LPG vehicle exhaust deceased from 41.3+/ 1.2MUg/m(3) (49.7+/-1.5%) to 32.8+/-1.4MUg/m(3) (38.8+/-1.7%) (p<0.05). In contrast, the contribution to VOCs made by gasoline and diesel vehicle exhaust and solvent usage increased (p<0.05). VOCs and nitric oxide (NO) in LPG source experienced the highest reductions at the roadside sites, while the variations were not significant at the urban and new town sites (p>0.05). For O3 production, LPG vehicle exhaust generally made a negative contribution (-0.17+/-0.06 ppbv) at the roadside sites, however it turned to a slightly positive contribution (0.004+/-0.038 ppbv) after the control measure. At the urban sites, although the reductions of VOCs and NO were minor (p>0.05), O3 produced by LPG vehicle significantly reduced from 4.19+/-1.92 ppbv to 0.95+/-0.38 ppbv (p<0.05). Meanwhile, O3 produced by LPG at the new town sites remained stable. The analysis of O3-precursor relationships revealed that alkenes and aromatics were the main species limiting roadside O3 formation, while aromatics were the most predominant controlling factor at urban and new town sites. In contrast, isoprene and sometimes NOx limited the O3 formation in rural environment. PMID- 27387809 TI - Examining the ecosystem health and sustainability of the world's largest mangrove forest using multi-temporal MODIS products. AB - Sweeping across Bangladesh and India, the Sundarbans forest is the world's largest contiguous mangrove forest. Although the human population density is high at the edge, Sundarbans has not encountered significant areal transformation in the last four decades. However, we argue that forest degradation can occur discontinuously within the forest without alteration of the entire forest area. In this paper, we used MODIS land products to compare the spatiotemporal ecological dynamics of the Bangladesh and Indian part of this mangrove forest between 2000 and 2010. We used the following 5 ecological parameters for our analysis: the Percent Tree Cover (PTC), Enhanced Vegetation Index (EVI), Net Primary Productivity (NPP), Leaf Area Index (LAI), and Evapotranspiration (ET). Our pixel-based time-series trend analysis for each MODIS image stack, using an ordinary least square (OLS) regression method, showed that forest degradation is happening in fragmented parcels within the forest. The degradation rate is comparatively higher in the Bangladesh part than in the Indian part of Sundarbans. Compartments 8, 10, 12, and 15 in the Bangladesh part, in particular, show high degradation, while compartment 48 and the southern edge of 45 show slight increases in PTC or EVI. Forest degradation in the Indian part of the forest is evident in the National Park and Reserve Forest blocks; however, no substantial degradation is evident in the western section. We have identified certain anthropogenic stressors (i.e., oil pollution, shrimp farming) and natural stressors (i.e., increased salinity, cyclones, forest fire) which might be responsible for the observed degradation. We have provided sustainable planning options and policy transformation alternatives for those areas under pressure from these stressors. We anticipate that our analysis of forest degradation will help management agencies, conservators, and policy makers achieve better management of this world's largest mangrove forest for a sustainable future. PMID- 27387810 TI - Modeling of irradiated graphite (14)C transfer through engineered barriers of a generic geological repository in crystalline rocks. AB - There are two RBMK-1500 type graphite moderated reactors at the Ignalina nuclear power plant in Lithuania, and they are under decommissioning now. The graphite cannot be disposed of in a near surface repository, because of large amounts of (14)C. Therefore, disposal of the graphite in a geological repository is a reasonable solution. This study presents evaluation of the (14)C transfer by the groundwater pathway into the geosphere from the irradiated graphite in a generic geological repository in crystalline rocks and demonstration of the role of the different components of the engineered barrier system by performing local sensitivity analysis. The speciation of the released (14)C into organic and inorganic compounds as well as the most recent information on (14)C source term was taken into account. Two alternatives were considered in the analysis: disposal of graphite in containers with encapsulant and without it. It was evaluated that the maximal fractional flux of inorganic (14)C into the geosphere can vary from 10(-11)y(-1) (for non-encapsulated graphite) to 10(-12)y(-1) (for encapsulated graphite) while of organic (14)C it was about 10(-3)y(-1) of its inventory. Such difference demonstrates that investigations on the (14)C inventory and chemical form in which it is released are especially important. The parameter with the highest influence on the maximal flux into the geosphere for inorganic (14)C transfer was the sorption coefficient in the backfill and for organic (14)C transfer - the backfill hydraulic conductivity. PMID- 27387811 TI - A review of groundwater contamination near municipal solid waste landfill sites in China. AB - Landfills are the most widely used method for municipal solid waste (MSW) disposal method in China. However, these facilities have caused serious groundwater contamination due to the leakage of leachate. This study, analyzed 32 scientific papers, a field survey and an environmental assessment report related to groundwater contamination caused by landfills in China. The groundwater quality in the vicinity of landfills was assessed as "very bad" by a comprehensive score (FI) of 7.85 by the Grading Method in China. Variety of pollutants consisting of 96 groundwater pollutants, 3 organic matter indicators, 2 visual pollutants and 6 aggregative pollutants had been detected in the various studies. Twenty-two kinds of pollutants were considered to be dominant. According to the Kruskal-Wallis test and the median test, groundwater contamination differed significantly between regions in China, but there were no significant differences between dry season and wet season measurements, except for some pollutants in a few landfill sites. Generally, the groundwater contamination appeared in the initial landfill stage after five years and peaked some years afterward. In this stage, the Nemerow Index (PI) of groundwater increased exponentially as landfill age increased at some sites, but afterwards decreased exponentially with increasing age at others. After 25years, the groundwater contamination was very low at selected landfills. The PI values of landfills decreased exponentially as the pollutant migration distance increased. Therefore, the groundwater contamination mainly appeared within 1000m of a landfill and most of serious groundwater contamination occurred within 200m. The results not only indicate that the groundwater contamination near MSW landfills should be a concern, but also are valuable to remediate the groundwater contamination near MSW landfills and to prevent the MSW landfill from secondary pollutions, especially for developing countries considering the similar situation of MSW disposal. PMID- 27387812 TI - Future electricity: The challenge of reducing both carbon and water footprint. AB - We estimate the consumptive water footprint (WF) of electricity and heat in 2035 for the four energy scenarios of the International Energy Agency (IEA) and a fifth scenario with a larger percentage of solar energy. Counter-intuitively, the 'greenest' IEA scenario (with the smallest carbon footprint) shows the largest WF increase over time: an increase by a factor four over the period 2010-2035. In 2010, electricity from solar, wind, and geothermal contributed 1.8% to the total. The increase of this contribution to 19.6% in IEA's '450 scenario' contributes significantly to the decrease of the WF of the global electricity and heat sector, but is offset by the simultaneous increase of the use of firewood and hydropower. Only substantial growth in the fractions of energy sources with small WFs - solar, wind, and geothermal energy - can contribute to a lowering of the WF of the electricity and heat sector in the coming decades. The fifth energy scenario - adapted from the IEA 450 scenario but based on a quick transition to solar, wind and geothermal energy and a minimum in bio-energy - is the only scenario that shows a strong decline in both carbon footprint (-66%) and consumptive WF (-12%) in 2035 compared to the reference year 2010. PMID- 27387813 TI - A four-year survey in the farming region of Chile, occurrence and human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans, and dioxin -like polychlorinated biphenyls in different raw meats. AB - For the first time in South America, a four-year survey (2011-2014) was conducted to assess the occurrence of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in different raw meats (bovine, pork, ovine, chicken, and turkey) sampled from ten of the fifteen regions of Chile. When expressed as pg World Health Organization Toxic Equivalent (WHO-TEQ2005)g-1 fat, the highest PCDD/F values for each species were 0.54 (bovine-2012), 0.27 (pork-2013), 0.23 (ovine-2011), 0.61 (chickens-2013), and 0.34 (turkey-2012). The highest mean dl-PCBs levels were 0.18 (bovine-2011), 0.05 (pork-2014), 0.13 (ovine-2011), 0.1 (chicken-2014), and 0.21 (turkey-2013). Penta and tetra-chlorinated congeners dominated PCDD/F WHO-TEQ2005 profiles during the survey, while PCB 126 dominated dl-PCBs profiles. Statistically significant interspecies differences were found. Dietary intake was also estimated, and the highest total PCDD/F and dl-PCBs values, found in poultry meat, were 0.09pgWHO TEQ2005kg-1bwd-1 (2013) for adults and 0.36pgWHO-TEQ2005kg-1bwd-1 (2013) for children. The concentrations and dietary intakes for the studied compounds in raw meat were below international and national maximum permitted limits. PMID- 27387815 TI - Post-stroke disability and its predictors among Nigerian stroke survivors. AB - BACKGROUND: Despite stroke is a major cause of disability, the predictors of the disability among stroke survivors has not been sufficiently delineated. OBJECTIVE: To assess post-stroke disability and determine its predictors among Nigerian stroke survivors. METHODS: This study involved 121 consecutive stroke survivors with at least 3 months of stroke from two tertiary health institutions in South-Western Nigeria. The World Health Organization Disability Assessment Schedule was used to assess their disability. Socio-demographic and clinical variables were obtained through interview and from their hospital records respectively. Poisson regression was used to examine the predictors. RESULTS: Moderate disability level (44.1 +/- 20.5) was observed among the participants. Prevalence of post-stroke disability was high in nine items with scores ranged between 62.0% and 90.1%. There was moderate prevalence of post-stroke disability in 3 items (44.6%-52.1%). When adjusted for sex, prevalence of post-stroke disability followed the same pattern. Being a male and having the affectation of dominant right limbs had 1.08 and 1.46 more likelihood of having disability while being gainfully employed after stroke had 0.81 less likelihood of having disability. Every additional unit of diastolic blood pressure and stroke duration were associated with estimated 0.4% and 0.2% less disability while every one year increased in age was associated with 0.5% increase in disability. CONCLUSION: Disability in stroke survivors is determined by having right dominant limb affected, increase in blood pressure, longer stroke duration, increase in age and being a male. However, disability in stroke survivors decreases with the stroke survivors engaging in productive lifestyle. PMID- 27387814 TI - Effect of CPPU on Carbohydrate and Endogenous Hormone Levels in Young Macadamia Fruit. AB - N-(2-Chloro-4-pyridyl)-N'-phenylurea (CPPU) is a highly active cytokinin-like plant growth regulator that promotes chlorophyll biosynthesis, cell division, and cell expansion. It also increases fruit set and accelerates fruit enlargement. However, there has been no report about the effect of CPPU on fruit development and its physiological mechanism in macadamia. In this study, we investigated the effect of CPPU treatment at early fruit development via foliar spray or raceme soaking at 20 mg.L-1 on fruit set and related physiology in macadamia. Changes in carbohydrate contents and endogenous hormones in leaves, bearing shoots and fruit were also examined. Results showed that CPPU significantly reduced young fruit drop and delayed the wave of fruit drop by 1-2 weeks. The treatment significantly decreased the contents of total soluble sugars and starch in the leaves, but increased them in the bearing shoots and total soluble sugars in the husk (pericarp) and seeds. These findings suggested that CPPU promoted carbohydrate mobilization from the leaves to the fruit. In addition, CPPU increased the contents of indole-3-acetic acid (IAA), gibberellin acid (GA3), and zeatin riboside (ZR) and decreased the abscisic acid (ABA) in the husk. Therefore, CPPU treatment reduced the early fruit drop by increasing carbohydrate availability and by modifying the balance among endogenous hormones. PMID- 27387816 TI - Community and social participation among adults with mobility impairments: A mixed methods study. AB - BACKGROUND: Community and social participation is a complex phenomenon that is influenced by personal and environmental factors and is linked to a good quality of life and well-being. Individuals with mobility impairments are at risk of experiencing limitations in participating in community activities due to a wide range of factors. OBJECTIVE: To understand community participation as defined by adults with mobility impairments and to examine relationships among factors that influence community participation. METHODS: A mixed-methods study design was used. In-depth interviews of 13 adults with mobility impairments were conducted and themes related to community participation were identified. Data from the Americans' Changing Lives Survey were used to construct variables that mimic the themes from the qualitative phase and structural equation modeling was used to examine the relationships among those variables including community participation. RESULTS: Individuals with mobility impairments identified health and function, neighborhood factors and self-efficacy as possible factors influencing participation in community activities. Findings from the SEM suggest a strong causal pathway between health and function and community and social participation. Neighborhood factors and health and function had a significant impact on self-efficacy, and a possible indirect effect through self-efficacy on community and social participation. CONCLUSIONS: Our study provides new empirical evidence that health and function have a significant impact on community and social participation. Our quantitative findings did not support the direct influence of neighborhood factors in community and social participation, yet these factors may have an indirect role by influencing the self-efficacy of individuals with mobility impairments. PMID- 27387817 TI - Effect of solution treatment on stress corrosion cracking behavior of an as forged Mg-Zn-Y-Zr alloy. AB - Effect of solid solution treatment (T4) on stress corrosion cracking (SCC) behavior of an as-forged Mg-6.7%Zn-1.3%Y-0.6%Zr (in wt.%) alloy has been investigated using slow strain rate tensile (SSRT) testing in 3.5 wt.% NaCl solution. The results demonstrated that the SCC susceptibility index (ISCC) of as forged samples was 0.95 and its elongation-to-failure (epsilonf) was only 1.1%. After T4 treatment, the SCC resistance was remarkably improved. The ISCC and epsilonf values of T4 samples were 0.86 and 3.4%, respectively. Fractography and surface observation indicated that the stress corrosion cracking mode for as forged samples was dominated by transgranular and partially intergranular morphology, whereas the cracking mode for T4 samples was transgranular. In both cases, the main cracking mechanism was associated with hydrogen embrittlement (HE). Through alleviating the corrosion attack of Mg matrix, the influence of HE on the SCC resistance of T4 samples can be greatly suppressed. PMID- 27387818 TI - Molecular characterization and antimicrobial resistance of STEC strains isolated from healthy cattle in 2011 and 2013 in Spain. AB - Prevention of Shiga toxin-producing Escherichia coli (STEC) foodborne outbreaks is hampered by its complex epidemiology. We assessed the distribution of virulence genes (VGs), main serogroups/serotypes for public health [haemolytic uraemic syndrome (HUS)-related], antimicrobial resistance (AMR) profiles and pulsed-field gel electrophoresis (PFGE) patterns in a collection of STEC isolates obtained from cattle hide (n = 149) and faecal (n = 406) samples collected during a national survey conducted in Spain in 2011 and 2013. Isolates were cultured using McConkey and CT-SMAC agar after enrichment, and confirmed as STEC by PCR. STEC prevalence in hides (15.4%) was higher than in faeces (10.7%) and O157:H7 was more frequent in the former (2.7% vs. 0.99%). Non-O157 HUS-related serogroups were present albeit at low frequencies. The non-O157 isolates were more heterogeneous than O157:H7 in their VG patterns, with 25/64 presenting VGs from both STEC and enterotoxigenic pathotypes (hybrid isolates). Of the STEC isolates, 62.5% were resistant at least to one antimicrobial, and no differences in AMR between O157:H7 and non-O157 were detected. All isolates had different profiles by PFGE and did not form a cluster. Overall, our results demonstrated that STEC in the cattle reservoir is still a matter of concern for human health due to the presence of HUS-related serogroups, the occurrence of certain VGs, AMR and the additional risks that hybrid isolates may pose, and thus warrants further investigation. PMID- 27387819 TI - Enhanced model-based design of a high-throughput three dimensional micromixer driven by alternating-current electrothermal flow. AB - We propose a 3D microfluidic mixer based on the alternating current electrothermal (ACET) flow. The ACET vortex is produced by 3D electrodes embedded in the sidewall of the microchannel and is used to stir the fluidic sample throughout the entire channel depth. An optimized geometrical structure of the proposed 3D micromixer device is obtained based on the enhanced theoretical model of ACET flow and natural convection. We quantitatively analyze the flow field driven by the ACET, and a pattern of electrothermal microvortex is visualized by the micro-particle imaging velocimetry. Then, the mixing experiment is conducted using dye solutions with varying solution conductivities. Mixing efficiency can exceed 90% for electrolytes with 0.2 S/m (1 S/m) when the flow rate is 0.364 MUL/min (0.728 MUL/min) and the imposed peak-to-peak voltage is 52.5 V (35 V). A critical analysis of our micromixer in comparison with different mixer designs using a comparative mixing index is also performed. The ACET micromixer embedded with sidewall 3D electrodes can achieve a highly effective mixing performance and can generate high throughput in the continuous-flow condition. PMID- 27387820 TI - Influence of Molecular Structure on the In Vivo Performance of Flexible Rod Polyrotaxanes. AB - Polyrotaxanes, a family of rod-shaped nanomaterials comprised of noncovalent polymer/macrocycle assemblies, are being used in a growing number of materials and biomedical applications. Their physiochemical properties can vary widely as a function of composition, potentially leading to different in vivo performance outcomes. We sought to characterize the pharmacokinetic profiles, toxicities, and protein corona compositions of 2-hydroxypropyl-beta-cyclodextrin polyrotaxanes as a function of variations in macrocycle threading efficiency, molecular weight, and triblock copolymer core structure. We show that polyrotaxane fate in vivo is governed by the structure and dynamics of their rodlike morphologies, such that highly threaded polyrotaxanes are long circulating and deposit in the liver, whereas lung deposition and rapid clearance is observed for species bearing lower 2-hydroxypropyl-beta-cyclodextrin threading percentages. Architecture differences also promote recruitment of different serum protein classes and proportions; however, physiochemical differences have little or no influence on their toxicity. These findings provide important structural insights for guiding the development of polyrotaxanes as scaffolds for biomedical applications. PMID- 27387821 TI - Effect of Buffer Conditions and Organic Cosolvents on the Rate of Strain-Promoted Azide-Alkyne Cycloaddition. AB - We investigate the effect of buffer identity, ionic strength, pH, and organic cosolvents on the rate of strain-promoted azide-alkyne cycloaddition with the widely used DIBAC cyclooctyne. The rate of reaction between DIBAC and a hydrophilic azide is highly tolerant to changes in buffer conditions but is impacted by organic cosolvents. Thus, bioconjugation reactions using DIBAC can be carried out in the buffer that is most compatible with the biomolecules being labeled, but the use of organic cosolvents should be carefully considered. PMID- 27387823 TI - High Rates of Bleeding Complications among Hospitalized Patients with Hereditary Hemorrhagic Telangiectasia in the United States. AB - RATIONALE: There is sparse published literature on the causes and outcomes of hospitalization of patients with hereditary hemorrhagic telangiectasia (HHT). OBJECTIVES: To evaluate rates of various complications, comorbidities, and in hospital outcomes of patients with HHT using a large, multihospital inpatient database. METHODS: We identified patients with HHT in the U.S. Nationwide Inpatient Sample between 2000 and 2012. Rates of hemorrhagic, neurological, hepatic, and cardiopulmonary complications among hospitalized patients with HHT were evaluated. We also studied procedure use rates for blood transfusion, endoscopy, and epistaxis treatment. Hospitalization outcomes, including in hospital mortality, discharge status, charges, and length of stay, were evaluated. MEASUREMENTS AND MAIN RESULTS: We identified 10,293 patients with HHT. The mean age of the HHT population was 60.7 years. Sixty percent of patients were female. More than 75% of HHT hospitalizations occurred in those older than 50 years of age. Patients with HHT had high rates of bleeding-related complications, including anemia (53.3%), epistaxis (16.2%), and gastrointestinal bleeding (10.8%). Overall, bleeding complications accounted for 62.7% of HHT-related complications. Thirty-eight percent of hospitalized patients with HHT received one or more transfusions of a blood product. Cardiopulmonary complications were present in 41.0% of the cases. Congestive heart failure was the second most common individual complication among patients with HHT, affecting 19.9% of patients. The in-hospital mortality rate was 1.9%. CONCLUSIONS: In this large, nationwide study, we found that nearly two-thirds of patients hospitalized with HHT experienced a bleeding-related complication. Nearly 40% of hospitalized patients with HHT required transfusion of blood products. Cardiopulmonary complications, including congestive heart failure, were the second most common complication. The high burden of bleeding-related complications points to a significant unmet clinical need for these patients. PMID- 27387822 TI - Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma. AB - OBJECTIVE: Intravoxel incoherent motion (IVIM) is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma. METHODS: Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were generated for contrast-enhancing regions (CER) and non-enhancing regions (NCER). Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses. RESULTS: We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10-3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively). Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031); fCER combined with treatment predicted survival with 100% accuracy. CONCLUSIONS: The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma. PMID- 27387824 TI - Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature. AB - BACKGROUND: Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. CASE PRESENTATION: A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8 degrees C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. CONCLUSIONS: In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option. PMID- 27387825 TI - Micrococcin P1, a naturally occurring macrocyclic peptide inhibiting hepatitis C virus entry in a pan-genotypic manner. AB - Hepatitis C virus (HCV) is considered a major public health concern worldwide. Despite recent advances in curing chronic hepatitis C, unmet medical needs still remain, especially due to the high economic burden of therapies. Accordingly, our study aimed to identify affordable novel HCV inhibitors by screening of natural product compound libraries. We identified micrococcin P1, a macrocyclic peptide antibiotic, inhibiting HCV entry in a pan-genotypic manner with an EC50 range of 0.1-0.5 MUM. Micrococcin P1 interfered with HCV entry at an attachment step. Furthermore, micrococcin P1 efficiently inhibited HCV spread by blocking cell free infection as well as cell-to-cell transmission, without affecting the secretion of infectious virions. Interestingly, the putative molecular target of micrococcin P1 is glycoprotein E2 (IIe-630-Thr), as revealed by selection for viral drug resistance. In addition, micrococcin P1 inhibited sofosbuvir-resistant HCV strains and showed synergy in combination with selected HCV drugs, suggesting an alternative treatment paradigm for patients. In conclusion, we identified micrococcin P1 as specifically inhibiting entry of all HCV genotypes and demonstrated that micrococcin P1 potentially could add value to therapies in combination with current HCV interventions. PMID- 27387826 TI - Development of a full-length cDNA-derived enterovirus A71 vaccine candidate using reverse genetics technology. AB - Enterovirus A71 (EV-A71) is responsible for epidemics of hand, foot and mouth disease (HFMD) in young children. To circumvent difficulties in obtaining clinical enterovirus isolates that might be contaminated with other viruses, a platform technology was developed to quickly generate vaccine virus strains based on the published enterovirus genomic sequences. A recombinant plasmid containing the full-length infectious cDNA clone of EV-A71 vaccine strain E59 was directly generated after transfecting the recombinant plasmid into Vero, RD or HEK293A cells, and phenotypic characteristics similar to the parental strain were observed. The cDNA-derived infectious EV-A71 virus grown in Vero cells produced relatively stable virus titers in both T-flasks and microcarrier culture systems. To evaluate the genetic stability of the cDNA-derived EV-A71 viruses, the immunodominant structural proteins, VP1 and VP2, of the recombinant EV-A71 viruses were sequenced and analyzed. The cDNA-derived EV-A71 virus showed weak pathogenicity in a human SCARB2 mouse model. These results show the successful generation of a recombinant virus derived from a published viral genomic sequence that demonstrated good genetic stability and viral yields, which could represent an efficient and safe vaccine strain for cGMP-grade manufacturing. PMID- 27387827 TI - Targeting the pseudorabies virus DNA polymerase processivity factor UL42 by RNA interference efficiently inhibits viral replication. AB - RNA interference (RNAi) is a conserved gene-silencing mechanism in which small interfering RNAs (siRNAs) induce the sequence-specific degradation of homologous RNAs. It has been shown to be a novel and effective antiviral therapy against a wide range of viruses. The pseudorabies virus (PRV) processivity factor UL42 can enhance the catalytic activity of the DNA polymerase and is essential for viral replication, thus it may represent a potential drug target of antiviral therapy against PRV infection. Here, we synthesized three siRNAs (siR-386, siR-517, and siR-849) directed against UL42 and determined their antiviral activities in cell culture. We first examined the kinetics of UL42 expression and found it was expressed with early kinetics during PRV replication. We verified that siR-386, siR-517, and siR-849 efficiently inhibited UL42 expression in an in vitro transfection system, thereby validating their inhibitory effects. Furthermore, we confirmed that these three siRNAs induced potent inhibitory effects on UL42 expression after PRV infection, comparable to the positive control siRNA, siR 1046, directed against the PRV DNA polymerase, the UL30 gene product, which is essential for virus replication. In addition, PRV replication was markedly reduced upon downregulation of UL42 expression. These results indicate that UL42 targeted RNAi efficiently inhibits target gene expression and impairs viral replication. This study provides a new clue for the design of an intervention strategy against herpesviruses by targeting their processivity factors. PMID- 27387828 TI - Isolation and characterization of a novel neutralizing antibody targeting the CD4 binding site of HIV-1 gp120. AB - Isolation and characterization of novel HIV-1 neutralizing antibodies assists the development of effective AIDS vaccines and immune therapeutics. In this study, we constructed a phage display antibody library by using the PBMC samples of a clade B' HIV-1-infected long-term nonprogressor (LTNP) whose sera exhibited broadly neutralizing activity. A novel human monoclonal antibody (hMAb), termed A16, was identified by panning the library with two clades of HIV-1 Env glycoproteins. We demonstrated that A16 neutralized 32% of 73 tested HIV-1 isolates and it targeted the CD4-binding site (CD4bs) of gp120 with high affinity. By selecting the peptide mimotopes in combination with computational algorithms and site-directed mutagenesis, the epitope of A16 was mapped to the structurally conserved sites located within the beta1-alpha1, loop D, beta20-beta21 (bridging sheet) and beta24-alpha5 of gp120, which critically determine the CD4 binding and are involved in the epitopes of CD4bs-directed antibodies. Our studies have shed new insights for the immune response of HIV-1 infection and offered a new tool for designing vaccine immunogens and antibody-based immune therapy. PMID- 27387829 TI - Failure of transplantation tolerance induction by autologous regulatory T cells in the pig-to-non-human primate islet xenotransplantation model. AB - BACKGROUND: Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. METHODS: Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University (SNU) miniature pigs with immunosuppression by anti-thymoglobulin (ATG), cobra venom factor, anti-CD154 monoclonal antibody (mAb), and sirolimus. CD4(+) CD25(high) CD127(low) autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40-CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. RESULTS: After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40 CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. CONCLUSIONS: Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to-NHP islet xenotransplantation setting. PMID- 27387832 TI - Onychophagia: A nail-biting conundrum for physicians. AB - Onychophagia, defined as habitual nail biting, is a common disorder affecting 20 30% of the population and all age groups. It may lead to significant psychosocial problems, have a negative impact on quality of life, and cause complications involving both the nail unit and the oral cavity. The objective of this paper is to review the prevalence, etiology, history, physical examination, complications and management of nail biting. Since onychophagia is a challenging disorder to treat, a multi-disciplinary approach should be taken involving dermatologists, internists, pediatricians, psychiatrists and dentists. PMID- 27387830 TI - Endoscopic Ultrasound for Preoperative Esophageal Squamous Cell Carcinoma: a Meta Analysis. AB - BACKGROUND: Treatment options and prognosis of esophageal squamous cell carcinoma (ESCC) depend on the primary tumor depth (T-staging) and regional lymph node status (N-staging). Endoscopic ultrasound (EUS) has emerged as a useful staging tool, but studies regarding its benefits have been variable. The objective of this study was to evaluate the diagnostic accuracy of EUS for detecting preoperative ESCC. METHODS: We included in our meta-analysis studies involving EUS-based staging of preoperative ESCC compared with pathological staging. Using a random-effects model, we performed a meta-analysis of the accuracy of EUS by calculating pooled estimates of sensitivity, specificity and the diagnostic odds ratio. In addition, we created a summary receiver operating characteristic (SROC) curve. RESULTS: Forty-four studies (n = 2880) met the inclusion criteria. The pooled sensitivity and specificity of T1 were 77% (95%CI: 73 to 80) and 95% (95%CI: 94 to 96). Among the T1 patients, EUS had a pooled sensitivity in differentiating T1a and T1b of 84% (95%CI: 80 to 88) and 83% (95%CI: 80 to 86), and a specificity of 91% (95%CI: 88 to 94) and 89% (95%CI: 86 to 92). To stage T4, EUS had a pooled sensitivity of 84% (95%CI: 79 to 89) and a specificity of 96% (95%CI: 95 to 97). The overall accuracy of EUS for T-staging was 79% (95%CI: 77 to 80), and for N-staging, 71% (95%CI: 69 to 73). CONCLUSIONS: EUS has good diagnostic accuracy for staging ESCC, which has better performance in T1 sub staging (T1a and T1b) and advanced disease (T4). PMID- 27387833 TI - Optimal flapping wing for maximum vertical aerodynamic force in hover: twisted or flat? AB - This work presents a parametric study, using the unsteady blade element theory, to investigate the role of twist in a hovering flapping wing. For the investigation, a flapping-wing system was developed to create a wing motion of large flapping amplitude. Three-dimensional kinematics of a passively twisted wing, which is capable of creating a linearly variable geometric angle of attack (AoA) along the wingspan, was measured during the flapping motion and used for the analysis. Several negative twist or wash-out configurations with different values of twist angle, which is defined as the difference in the average geometric AoAs at the wing root and the wing tip, were obtained from the measured wing kinematics through linear interpolation and extrapolation. The aerodynamic force generation and aerodynamic power consumption of these twisted wings were obtained and compared with those of flat wings. For the same aerodynamic power consumption, the vertical aerodynamic forces produced by the negatively twisted wings are approximately 10%-20% less than those produced by the flat wings. However, these twisted wings require approximately 1%-6% more power than flat wings to produce the same vertical force. In addition, the maximum-force producing twisted wing, which was found to be the positive twist or wash-in configuration, was used for comparison with the maximum-force-producing flat wing. The results revealed that the vertical aerodynamic force and aerodynamic power consumption of the two types of wings are almost identical for the hovering condition. The power loading of the positively twisted wing is only approximately 2% higher than that of the maximum-force-producing flat wing. Thus, the flat wing with proper wing kinematics (or wing rotation) can be regarded as a simple and efficient candidate for the development of hovering flapping-wing micro air vehicle. PMID- 27387831 TI - Erratum to: An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A. PMID- 27387834 TI - Endotoxin-induced inflammation in a rodent model up-regulates IL-1a expression and CD45+ leukocyte recruitment and increases the rate of reepithelialization and wound closure. AB - Wound healing is traditionally divided into inflammation, proliferation, and remodeling phases. Several inflammatory mediators and cells regulate the inflammation phase. The specific roles for different mediators have not been clearly defined. The effects of inflammation phase modulation on wound healing were evaluated in this study. Rat full-thickness wounds were divided into different experimental groups: (1) sterile hyper-inflammatory wounds/endotoxin (topical endotoxin), (2) sterile hypo-inflammatory/inhibitor group (cocktail of topical COX-1 plus COX-2 plus lipoxygenase inhibitors), and (3) control groups: topical saline or DMSO. After full-thickness wound creation, custom-made titanium chambers enclosed the wound, creating an isolated well-controlled environment. Wound healing was followed over time; tissue biopsies and wound fluid samples were collected on days 1, 4, and 8 postoperatively. The validity of the inflammation model was confirmed by increased IL-1a expression, increased CD45+ leukocytes recruitment in the hyper-inflamed group as compared to the inhibitor and control groups. The reepithelialization percentage was significantly increased in the endotoxin group as compared to the inhibitor group on day 4 (60.75 vs. 22.05, p-value <0.05) and both the inhibitor and the control group on day 8 (control group: 63.2%, inhibitor group: 28.9%, endotoxin group: 84.2%, p value <0.05). Also, the macroscopic wound closure was increased in the endotoxin group as compared to the inhibitor group and control group both on day 4 (control group: 69.9%, inhibitor group: 62.9%, endotoxin group: 81.9%, p-value <0.05) and on day 8 (control group: 68.5%, inhibitor group: 69.1%, endotoxin group: 83.7%, p value <0.05). Endotoxin-induced sterile inflammation up-regulates IL-1a expression and CD45+ leukocyte recruitment and results in faster rate of wound reepithelialization and wound closure in full-thickness rodent wounds. Conversely, the wound reepithelialization and wound closure can be significantly delayed on treatment with a combination of cyclooxygenase and lipoxygenase inhibitors. PMID- 27387835 TI - CMI reinforces its ties with ESCMID. PMID- 27387836 TI - Moving Beyond Self-Report: Implicit Associations about Death/Life Prospectively Predict Suicidal Behavior among Veterans. AB - Reliance on self-report limits clinicians' ability to accurately predict suicidal behavior. In this study the predictive validity of an objective measure, the death/suicide Implicit Association Test (d/sIAT), was tested among psychiatrically hospitalized veterans. Following acute stabilization, 176 participants completed the d/sIAT and traditional suicide risk assessments. Participants had similar d/sIAT scores regardless of whether they had recently attempted suicide. However, d/sIAT scores significantly predicted suicide attempts during the 6-month follow-up above and beyond other known risk factors for suicidal behavior (OR = 1.89; 95% CI: 1.15-3.12; based on 1SD increase). The d/sIAT may augment the accuracy of suicide risk assessment. PMID- 27387837 TI - Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application. AB - Gene therapy has the potential to provide innovative treatments for genetic and non-genetic diseases, with the ability to auto-regulate expression levels of therapeutic molecules so that they are produced locally and in direct response to disease activity. Generating disease responsive gene therapy vectors requires knowledge of the activation profile of transcription factors (TFs) during active disease, in order to assemble binding sites for these TFs into synthetic promoters, which can be appropriately activated by the disease process. In this study, we optimised a PCR random assembly approach to generate promoters with optimal spacing between TF binding sites (TFBSs) and their distance from the TATA box. In promoters with optimal spacing, it was possible to demonstrate activation by individual transcription pathways and either additive or synergistic promoter activation when transfected cells were treated with combined stimuli. The kinetics and sensitivity of promoter activation was further explored in transduced cells and when lentivirus was directly delivered to mouse paws a synthetic promoter demonstrated excellent activation by real-time imaging in response to local inflammation. PMID- 27387838 TI - Structure-Guided Control of siRNA Off-Target Effects. AB - Short interfering RNAs (siRNAs) are promising therapeutics that make use of the RNA interference (RNAi) pathway, but liabilities arising from the native RNA structure necessitate chemical modification for drug development. Advances in the structural characterization of components of the human RNAi pathway have enabled structure-guided optimization of siRNA properties. Here we report the 2.3 A resolution crystal structure of human Argonaute 2 (hAgo2), a key nuclease in the RNAi pathway, bound to an siRNA guide strand bearing an unnatural triazolyl nucleotide at position 1 (g1). Unlike natural nucleotides, this analogue inserts deeply into hAgo2's central RNA binding cleft and thus is able to modulate pairing between guide and target RNAs. The affinity of the hAgo2-siRNA complex for a seed-only matched target was significantly reduced by the triazolyl modification, while the affinity for a fully matched target was unchanged. In addition, siRNA potency for off-target repression was reduced (4-fold increase in IC50) by the modification, while on-target knockdown was improved (2-fold reduction in IC50). Controlling siRNA on-target versus microRNA (miRNA)-like off target potency by projection of substituent groups into the hAgo2 central cleft from g1 is a new approach to enhance siRNA selectivity with a strong structural rationale. PMID- 27387839 TI - The Validity of Discharge Billing Codes Reflecting Severe Maternal Morbidity. AB - BACKGROUND: Discharge diagnoses are used to track national trends and patterns of maternal morbidity. There are few data regarding the validity of the International Classification of Diseases (ICD) codes used for this purpose. The goal of our study was to try to better understand the validity of administrative data being used to monitor and assess trends in morbidity. METHODS: Hospital stay billing records were queried to identify all delivery admissions at the Massachusetts General Hospital for the time period 2001 to 2011 and the University of Michigan Health System for the time period 2005 to 2011. From this, we identified patients with ICD-9-Clinical Modification (CM) diagnosis and procedure codes indicative of severe maternal morbidity. Each patient was classified with 1 of 18 different medical/obstetric categories (conditions or procedures) based on the ICD-9-CM code that was recorded. Within each category, 20 patients from each institution were selected at random, and the corresponding medical charts were reviewed to determine whether the ICD-9-CM code was assigned correctly. The percentage of correct codes for each of 18 preselected clinical categories was calculated yielding a positive predictive value (PPV) and 99% confidence interval (CI). RESULTS: The overall number of correctly assigned ICD-9 CM codes, or PPV, was 218 of 255 (86%; CI, 79%-90%) and 154 of 188 (82%; CI, 74% 88%) at Massachusetts General Hospital and University of Michigan Health System, respectively (combined PPV, 372/443 [84%; CI, 79-88%]). Codes within 4 categories (Hysterectomy, Pulmonary edema, Disorders of fluid, electrolyte and acid-base balance, and Sepsis) had a 99% lower confidence limit >=75%. Codes within 8 additional categories demonstrated a 99% lower confidence limit between 74% and 50% (Acute respiratory distress, Ventilation, Other complications of obstetric surgery, Disorders of coagulation, Cardiomonitoring, Acute renal failure, Thromboembolism, and Shock). Codes within 6 clinical categories demonstrated a 99% lower confidence limit <50% (Puerperal cerebrovascular disorders, Conversion of cardiac rhythm, Acute heart failure [includes arrest and fibrillation], Eclampsia, Neurotrauma, and Severe anesthesia complications). CONCLUSIONS: ICD-9 CM codes capturing severe maternal morbidity during delivery hospitalization demonstrate a range of PPVs. The PPV was high when objective supportive evidence, such as laboratory values or procedure documentation supported the ICD-9-CM code. The PPV was low when greater judgment, interpretation, and synthesis of the clinical data (signs and symptoms) was required to support a code, such as with the category Severe anesthesia complications. As a result, these codes should be used for administrative research with more caution compared with codes primarily defined by objective data. PMID- 27387840 TI - Capturing Essential Information to Achieve Safe Interoperability. AB - In this article, we describe the role of "clinical scenario" information to assure the safety of interoperable systems, as well as the system's ability to deliver the requisite clinical functionality to improve clinical care. Described are methods and rationale for capturing the clinical needs, workflow, hazards, and device interactions in the clinical environment. Key user (clinician and clinical engineer) needs and system requirements can be derived from this information, therefore, improving the communication from clinicians to medical device and information technology system developers. This methodology is intended to assist the health care community, including researchers, standards developers, regulators, and manufacturers, by providing clinical definition to support requirements in the systems engineering process, particularly those focusing on development of Integrated Clinical Environments described in standard ASTM F2761. Our focus is on identifying and documenting relevant interactions and medical device capabilities within the system using a documentation tool called medical device interface data sheets and mitigating hazardous situations related to workflow, product usability, data integration, and the lack of effective medical device-health information technology system integration to achieve safe interoperability. Portions of the analysis of a clinical scenario for a "patient controlled analgesia safety interlock" are provided to illustrate the method. Collecting better clinical adverse event information and proposed solutions can help identify opportunities to improve current device capabilities and interoperability and support a learning health system to improve health care delivery. Developing and analyzing clinical scenarios are the first steps in creating solutions to address vexing patient safety problems and enable clinical innovation. A Web-based research tool for implementing a means of acquiring and managing this information, the Clinical Scenario RepositoryTM (MD PnP Program), is described. PMID- 27387841 TI - The melatonin-sensitive circadian clock of the enteric bacterium Enterobacter aerogenes. AB - Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26 degrees C to 40 degrees C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves. PMID- 27387842 TI - Immunogenomics of gastrointestinal nematode infection in ruminants - breeding for resistance to produce food sustainably and safely. AB - Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes. PMID- 27387843 TI - Blurring emotional memories using eye movements: individual differences and speed of eye movements. AB - BACKGROUND: In eye movement desensitization and reprocessing (EMDR), patients make eye movements (EM) while recalling traumatic memories. Making EM taxes working memory (WM), which leaves less resources available for imagery of the memory. This reduces memory vividness and emotionality during future recalls. WM theory predicts that individuals with small working memory capacities (WMCs) benefit more from low levels of taxing (i.e., slow EM) whereas individuals with large WMC benefit more from high levels of taxing (i.e., fast EM). OBJECTIVE: We experimentally examined and tested four prespecified hypotheses regarding the role of WMC and EM speed in reducing emotionality and vividness ratings: 1) EM regardless of WMC and EM speed-are more effective compared to no dual task, 2) increasing EM speed only affects the decrease in memory ratings irrespective of WMC, 3) low-WMC individuals-compared to high-WMC individuals-benefit more from making either type of EM, 4) the EM intervention is most effective when-as predicted by WM theory-EM are adjusted to WMC. METHOD: Undergraduates with low (n=31) or high (n=35) WMC recalled three emotional memories and rated vividness and emotionality before and after each condition (recall only, recall + slow EM, and recall + fast EM). RESULTS: Contrary to the theory, the data do not support the hypothesis that EM speed should be adjusted to WMC (hypothesis 4). However, the data show that a dual task in general is more effective in reducing memory ratings than no dual task (hypothesis 1), and that a more cognitively demanding dual task increases the intervention's effectiveness (hypothesis 2). CONCLUSIONS: Although adjusting EM speed to an individual's WMC seems a straightforward clinical implication, the data do not show any indication that such a titration is helpful. PMID- 27387844 TI - The use of EMDR in positive verbal material: results from a patient study. AB - BACKGROUND: According to the working memory (WM) theory of eye movement desensitisation and reprocessing (EMDR), dual tasks that tax WM during memory recall reduce image vividness and emotionality of memory during future recalls when no dual task is carried out. There is some evidence that WM taxing also reduces vividness and emotionality of auditory or verbal imagery. OBJECTIVE: The present study tests the effect of eye movements (EM) on positive verbal material (verbal imagery), which is used in different parts of the EMDR protocol. In the Dutch version of the standard EMDR protocol, a procedure "Positive Closure" (PC) is performed, which uses verbal imagery under dual task condition (EM). The value of EM in this procedure has not been established and according to the WM account would be counterproductive. Two earlier studies with undergraduates, with a set up comparable to the present one, showed no additive value of the EM in the procedure, but no counterproductive effect either. METHOD: Thirty-six patients rated the belief in possessing two positive personality traits and emotionality of the traits. They then had an EMDR session targeting a negative memory and recalled and re-rated the belief and emotionality of the traits afterward. Subsequently, they recalled one trait while dual tasking (EM) and the other trait without dual tasking. Afterward, they re-rated the belief and emotionality. RESULTS: EM did not affect the belief in possessing the trait or the emotionality. Secondary analysis shows an effective EMDR session itself enhances the belief in the traits, compared to a less or non-effective EMDR session. CONCLUSIONS: EM are not effective in enhancing the belief in possessing a personality trait or the emotionality. If replicated by other patient studies, this suggests elimination of the PC procedure. PMID- 27387845 TI - The effects of eye movements on emotional memories: using an objective measure of cognitive load. AB - BACKGROUND: Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. The working memory (WM) theory explains its efficacy: recall of an aversive memory and making eye movements (EM) both produce cognitive load, and competition for the limited WM resources reduces the memory's vividness and emotionality. The present study tested several predictions from WM theory. OBJECTIVE: We hypothesized that 1) recall of an aversive autobiographical memory loads WM compared to no recall, and 2) recall with EM reduces the vividness, emotionality, and cognitive load of recalling the memory more than only recall or only cognitive effort (i.e., recall of an irrelevant memory with EM). METHOD: Undergraduates (N=108) were randomly assigned to one of three conditions: 1) recall relevant memory with EM, 2) recall relevant memory without EM, and 3) recall irrelevant memory with EM. We used a random interval repetition task to measure the cognitive load of recalling the memory. Participants responded to randomly administered beeps, with or without recalling the memory. The degree to which participants slow down during recall provides an index of cognitive load. We measured the cognitive load and self-reported vividness and emotionality before, halfway through (8*24 s), and after (16*24 s) the intervention. RESULTS: Reaction times slowed down during memory recall compared to no recall. The recall relevant with EM condition showed a larger decrease in self-reported vividness and emotionality than the control conditions. The cognitive load of recalling the memory also decreased in this condition but not consistently more than in the control conditions. CONCLUSIONS: Recall of an aversive memory loads WM, but drops in vividness and emotionality do not immediately reduce the cognitive load of recalling the memory. More research is needed to find objective measures that could capture changes in the quality of the memory. PMID- 27387846 TI - Pediatric seizure-related posttraumatic stress and anxiety symptoms treated with EMDR: a case series. AB - PURPOSE: To examine the potential effects of eye movement desensitization and reprocessing (EMDR) in children with epilepsy-related posttraumatic stress and/or anxiety symptoms, using a case series design. METHODS: Five children (aged 8-18) with epilepsy identified for seizure-related posttraumatic stress and/or anxiety symptoms were treated with EMDR. To examine potential treatment effects, posttraumatic stress and anxiety symptoms were assessed (CRTI and SCARED) pre- and post-EMDR and at 3-month follow-up. Normative deviation scores were calculated to examine the severity of seizure-related posttraumatic stress and anxiety symptoms over time. The reliable change index was calculated for pre- to posttreatment change of seizure-related posttraumatic stress and/or anxiety symptoms. RESULTS: Before EMDR, overall or subscale scores indicated that all children had (sub)clinical seizure-related posttraumatic stress symptoms and/or anxiety symptoms. Directly after EMDR, most children showed significant and/or clinical individual improvement, and these beneficial effects were maintained or reached at follow-up. The mean number of sessions was 2 (range 1-3, 45 min per session). CONCLUSIONS: In case of seizure-related posttraumatic stress and/or anxiety, this study indicates that EMDR is a potentially successful quick and safe psychological treatment for children with epilepsy. PMID- 27387847 TI - Erasing memory traces of trauma with eye movement desensitization and reprocessing therapy. PMID- 27387848 TI - Topological Defects at the Graphene/h-BN interface Abnormally Enhance Its Thermal Conductance. AB - Low thermal conductance across interface is often the limiting factor in managing heat in many advanced device applications. The most commonly used approach to enhance the thermal conductance is to reduce/eliminate the interfacial structural defects. Using a graphene/h-BN (Gr/h-BN) interface, we show surprisingly that topological defects are able to enhance the thermal conductance across the interface. It is found that the phonon transmission across the Gr/h-BN interface with 5|7 defects is higher than that of the pristine interface, which is in strong contrast to the common notion that interface defects promote phonon scattering. By analyzing the strain distribution and phonon vibrational spectra, we find that this abnormal enhancement in interfacial thermal conductance originates from the localization of the stress fields arising from misfit dislocations and their out-of-plane deformations at the interface. In the presence of the defects, the overall mismatch strain is reduced. In addition, the out-of-plane deformations screen the long-ranged dislocation strain fields, resulting in the stress fields to be localized only at the cores of the defects. This abnormal mechanism provides a new dimension to enhance the interfacial thermal conductance in two-dimensional heterostructures. PMID- 27387849 TI - Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery. AB - BACKGROUND: Cataract is the leading cause of blindness in the world, and cataract surgery is one of the most commonly performed operations in the Western world. Preferred surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond laser platforms that can accurately and reproducibly perform key steps in cataract surgery, including corneal incisions, capsulotomy and lens fragmentation, are now available. The potential advantages of laser-assisted surgery are broad, and include greater safety and better visual outcomes through greater precision and reproducibility. OBJECTIVES: To compare the effectiveness of laser-assisted cataract surgery with standard ultrasound phacoemulsification cataract surgery by gathering evidence on safety from randomised controlled trials (RCTs). SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2016), EMBASE (January 1980 to May 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the U.S. Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2016. SELECTION CRITERIA: We included randomised controlled trials where laser-assisted cataract surgery was compared to standard ultrasound phacoemulsification cataract surgery. We graded the certainty of the evidence using GRADE. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule and posterior capsule tears. The secondary outcomes were visual acuity (corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA)), refractive outcomes, quality of vision (as measured by any validated visual function score), postoperative complications and cost-effectiveness. MAIN RESULTS: We included 16 RCTs conducted in Germary, Hungary, Italy, India, China and Brazil that enrolled a total of 1638 eyes of 1245 adult participants. Overall, the studies were at unclear or high risk of bias. In 11 of the studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Five of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data.The number of anterior capsule and posterior capsule tears reported in the included studies for both laser cataract surgery and manual phacoemulsification cataract surgery were low. There were four anterior capsule tears and one posterior capsule tear in 1076 eyes reported in 10 studies (2 anterior capsule tears in laser arms, 2 anterior capsule tears and 1 posterior capsule tear in standard phacoemulsification arms). We are very uncertain as to the effect of laser-assisted surgery compared to standard phacoemulsification surgery with respect to these two outcomes. For postoperative cystoid macular oedema and elevated postoperative intraocular pressures, again the evidence was inconclusive (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.20 to 1.68; 957 eyes, 9 studies, low certainty evidence; and OR 0.57, 95% CI 0.11 to 2.86; 903 eyes, 8 studies, low certainty evidence).We found little evidence of any important difference in postoperative visual acuity between laser-assisted and standard phacoemulsification arms. There was a small advantage for laser-assisted cataract surgery at six months in CDVA. However, the mean difference (MD) was -0.03 logMAR (95% CI -0.05 to -0.00; 224 eyes, 3 studies, low certainty evidence) which is equivalent to 1.5 logMAR letters and is therefore, clinically insignificant. No studies reported patient reported outcome measures such as visual function.There were no data reported on costs or resource use but three studies reported the time taken to do the surgery. There was little evidence of any major difference between the two procedures in this respect (MD 0.1 minutes, 95% CI -0.02 to 0.21; 274 eyes, low certainty evidence). AUTHORS' CONCLUSIONS: The evidence from the 16 randomised controlled trials RCTs included in this review could not determine the equivalence or superiority of laser-assisted cataract surgery compared to standard manual phacoemulsification for our chosen outcomes due to the low to very low certainty of the evidence available from these studies. As complications occur rarely, large, adequately powered, well designed, independent RCTs comparing the safety and efficacy of laser-assisted cataract surgery with standard phacoemulsification cataract surgery are needed. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis. Data on patient-reported outcomes and cost effectiveness are needed. Paired-eye studies should be analysed and reported appropriately. PMID- 27387850 TI - Rituximab for eradicating inhibitors in people with acquired haemophilia A. AB - BACKGROUND: Acquired haemophilia A is a rare bleeding disorder caused by the development of specific autoantibodies against coagulation factor VIII. Rituximab may be an alternative approach to the treatment of acquired haemophilia by eradicating FVIII autoantibodies. OBJECTIVES: To assess and summarise the efficacy and adverse effects of rituximab for treating people with acquired haemophilia A. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's trials registers, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's trials registers: 01 March 2016. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of rituximab for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. DATA COLLECTION AND ANALYSIS: No trials matching the selection criteria were eligible for inclusion. MAIN RESULTS: No trials matching the selection criteria were eligible for inclusion. AUTHORS' CONCLUSIONS: No randomised clinical trials of rituximab for acquired hemophilia A were found. Thus, based on the highest quality of evidence, we are not able to draw any conclusions or make any recommendations on rituximab for eradicating inhibitors in people with acquired haemophilia A. Given that undertaking randomised controlled trials in this field is a complex task, the authors suggest that, while planning such trials, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence. The authors plan, for a future update of this review, to appraise and incorporate any randomised controlled trials, as well as other high-quality non-randomised studies. PMID- 27387851 TI - A Bilayered Structure Comprised of Functionalized Carbon Nanotubes for Desalination by Membrane Distillation. AB - The development of a novel carbon nanotube (CNT) immobilized membrane comprised of a double-layer structure is presented for water desalination by membrane distillation. The bilayered structure is comprised of CNTs functionalized with a hydrophobic octadecyl amine group on the feed side and carboxylated CNTs on the permeate side. The latter is more hydrophilic. The hydrophobic CNTs provide higher water vapor permeation, while the hydrophilic CNTs facilitate the condensation of water vapor. Together, these led to superior performance, and flux in a direct contact membrane distillation mode was found to be as high as 121 kg/m(2)h at 80 degrees C. The bilayered membrane represented an enhancement of 70% over the unmodified membrane and 37% over a membrane which had a monolayered structure where only the feed side was CNT-modified. PMID- 27387852 TI - Early salvage radiation therapy post-prostatectomy: key considerations. AB - Post-prostatectomy radiotherapy (RT) is commonly employed to maximize oncologic outcomes in patients with pathologic adverse features (adjuvant RT]) or to treat men with prostate-specific antigen or local recurrence after initial observation (salvage RT [SRT]). Randomized controlled trials have been unable to compare adjuvant RT versus SRT; however, there is growing retrospective evidence that observation and early SRT (eSRT) may be a suitable. The issue of patient selection is crucial; several clinical tools and some newer biomarker-based tools might help in this process. Moreover, the optimal prostate-specific antigen threshold for eSRT, the RT dose, the irradiation field and the use of hormonal therapy are still open questions. In this article, we review the current literature on eSRT and provide some insights on what's happening for the future. PMID- 27387854 TI - Home-related injuries among under-five-year children and mothers' care regarding injury prevention in rural areas. AB - This cross-sectional study was conducted in rural areas of Twiserkan (Toyserkan) County, in Iran, to assess factors associated with home-related injuries among under-five-year children and their mothers' care regarding injury prevention. Mothers who had their under-five-year-old children injured within a 12-month period were identified from recorded information in Twiserkan Health Center. Then, data were gathered using pre-tested questionnaire and through interview with injured children's mothers. The questions were about characteristics of the children's injuries and their mothers' care regarding injury prevention, using PRECEDE (Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation) model with focus on knowledge and attitude; enabling and reinforcing factors; and mothers' preventive behaviours. The study results showed that 197 out of 210 total identified mothers took part in the study. The reported injuries were 11.68%, 39.09%, and 49.24%, respectively, for severe, moderate, and mild cases. Fall was the most frequent injury with 35%. Among PRECEDE model constructs, there was a statistically significant correlation between mothers' knowledge and injury severity among children. Home-related injuries are an important health problem among study population and their prediction and prevention are necessary. Enhancement of mothers' knowledge can be helpful to improve child injury prevention. PMID- 27387853 TI - Structural and Mechanical Properties of Amyloid Beta Fibrils: A Combined Experimental and Theoretical Approach. AB - In this combined experimental (deep ultraviolet resonance Raman (DUVRR) spectroscopy and atomic force microscopy (AFM)) and theoretical (molecular dynamics (MD) simulations and stress-strain (SS)) study, the structural and mechanical properties of amyloid beta (Abeta40) fibrils have been investigated. The DUVRR spectroscopy and AFM experiments confirmed the formation of linear, unbranched and beta-sheet rich fibrils. The fibrils (Abeta40)n, formed using n monomers, were equilibrated using all-atom MD simulations. The structural properties such as beta-sheet character, twist, interstrand distance, and periodicity of these fibrils were found to be in agreement with experimental measurements. Furthermore, Young's modulus (Y) = 4.2 GPa computed using SS calculations was supported by measured values of 1.79 +/- 0.41 and 3.2 +/- 0.8 GPa provided by two separate AFM experiments. These results revealed size dependence of structural and material properties of amyloid fibrils and show the utility of such combined experimental and theoretical studies in the design of precisely engineered biomaterials. PMID- 27387856 TI - Occupational health training in India: Need for a competency-driven approach. AB - BACKGROUND: In order to cater to the changing business scenario, employment and education profiles of labor, newer occupations, and emerging occupational health challenges, it is time to improve the performance of occupational health professionals by adapting core professional competencies while drawing on global knowledge. OBJECTIVE: To delineate the competencies required for medical graduates, medical postgraduates, and Masters in Public Health (MPH) graduates practicing occupational health in India. MATERIALS AND METHODS: First, offline and online literature searches were carried out to enlist the core competencies for occupational health. A draft template was prepared for the identified competencies and stakeholders were asked to rank the listed competencies on a three-point scale stating must, desirable, and not required for each of the three categories of professionals, i.e., medical graduates, medical postgraduates, and MPH graduates. RESULTS: Through the extensive literature search, 23 competencies were identified for occupational health practitioners. According to stakeholders, five competencies were a must, nine were desirable, and nine were not required by a medical graduate. Similarly for a medical postgraduate, except the ability to judge the ergonomic design of the workplace and working tools, which is considered desirable, all other competencies were considered a must while for an MPH graduate all the enlisted 23 competencies were considered a must by the stakeholders. CONCLUSION: The framework of occupational health competencies developed through this research can be used to strengthen the training of occupational health professionals in India. PMID- 27387855 TI - The RNA Chaperone Hfq Is Essential for Virulence and Modulates the Expression of Four Adhesins in Yersinia enterocolitica. AB - In Enterobacteriaceae, the RNA chaperone Hfq mediates the interaction of small RNAs with target mRNAs, thereby modulating transcript stability and translation. This post-transcriptional control helps bacteria adapt quickly to changing environmental conditions. Our previous mutational analysis showed that Hfq is involved in metabolism and stress survival in the enteropathogen Yersinia enterocolitica. In this study we demonstrate that Hfq is essential for virulence in mice and influences production of surface pathogenicity factors, in particular lipopolysaccharide and adhesins mediating interaction with host tissue. Hfq inhibited the production of Ail, the Ail-like protein OmpX and the MyfA pilin post-transcriptionally. In contrast Hfq promoted production of two major autotransporter adhesins YadA and InvA. While protein secretion in vitro was not affected, hfq mutants exhibited decreased protein translocation by the type III secretion system into host cells, consistent with decreased production of YadA and InvA. The influence of Hfq on YadA resulted from a complex interplay of transcriptional, post-transcriptional and likely post-translational effects. Hfq regulated invA by modulating the expression of the transcriptional regulators rovA, phoP and ompR. Therefore, Hfq is a global coordinator of surface virulence determinants in Y. enterocolitica suggesting that it constitutes an attractive target for developing new antimicrobial strategies. PMID- 27387857 TI - Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths - United States, 2002-2014. AB - Use of the prescription opioid methadone for treatment of pain, as opposed to treatment of opioid use disorder (e.g., addiction), has been identified as a contributor to the U.S. opioid overdose epidemic. Although methadone accounted for only 2% of opioid prescriptions in 2009 (1), it was involved in approximately 30% of overdose deaths. Beginning with 2006 warnings from the Food and Drug Administration (FDA), efforts to reduce methadone use for pain have accelerated (2,3). The Office of the Assistant Secretary for Planning and Evaluation of the U.S. Department of Health and Human Services and CDC analyzed methadone distribution, reports of diversion (the transfer of legally manufactured methadone into illegal markets), and overdose deaths during 2002-2014. On average, the rate of grams of methadone distributed increased 25.1% per year during 2002-2006 and declined 3.2% per year during 2006-2013. Methadone-involved overdose deaths increased 22.1% per year during 2002-2006 and then declined 6.5% per year during 2006-2014. During 2002-2006, rates of methadone diversion increased 24.3% per year; during 2006-2009, the rate increased at a slower rate, and after 2009, the rate declined 12.8% per year through 2014. Across sex, most age groups, racial/ethnic populations, and U.S. Census regions, the methadone overdose death rate peaked during 2005-2007 and declined in subsequent years. There was no change among persons aged >=65 years, and among persons aged 55-64 years the methadone overdose death rate continued to increase through 2014. Additional clinical and public health policy changes are needed to reduce harm associated with methadone use for pain, especially among persons aged >=55 years. PMID- 27387858 TI - Opposing PKA and Hog1 signals control the post-transcriptional response to glucose availability in Cryptococcus neoformans. AB - The pathogenic fungus Cryptococcus neoformans must adapt to glucose-limited conditions in the lung and glucose replete conditions upon dissemination to the brain. We report that glucose controls ribosome biogenesis and translation by modulating mRNA decay through a balance of PKA and Hog1 signalling. Glucose signalling through PKA stabilized ribosomal protein (RP) mRNAs whereas glucose starvation destabilized RP transcripts through Hog1. Glucose starvation-induced oxidative stress response genes, and treatment of glucose-fed cells with reactive oxygen species (ROS) generating compounds repressed RP transcripts, both of which were dependent on Hog1. Stabilization of RP transcripts led to retention of polysomes in a hog1Delta mutant, whereas stabilization of RP transcripts by cyclic AMP did not affect translation repression, suggesting that Hog1 alone signals translation repression. In sum, this work describes a novel antagonism between PKA and Hog1 controlling ribosome biogenesis via mRNA stability in response to glucose availability in this important human pathogen. PMID- 27387860 TI - Hemodynamic Flow-Induced Mechanotransduction Signaling Influences the Radiation Response of the Vascular Endothelium. AB - Hemodynamic shear stress is defined as the physical force exerted by the continuous flow of blood in the vascular system. Endothelial cells, which line the inner layer of blood vessels, sense this physiological force through mechanotransduction signaling and adapt to maintain structural and functional homeostasis. Hemodynamic flow, shear stress and mechanotransduction signaling are, therefore, an integral part of endothelial pathophysiology. Although this is a well-established concept in the cardiovascular field, it is largely dismissed in studies aimed at understanding radiation injury to the endothelium and subsequent cardiovascular complications. We and others have reported on the differential response of the endothelium when the cells are under hemodynamic flow shear compared with static culture. Further, we have demonstrated significant differences in the gene expression of static versus shear-stressed irradiated cells in four key pathways, reinforcing the importance of shear stress in understanding radiation injury of the endothelium. This article further emphasizes the influence of hemodynamic shear stress and the associated mechanotransduction signaling on physiological functioning of the vascular endothelium and underscores its significance in understanding radiation injury to the vasculature and associated cardiac complications. Studies of radiation effect on endothelial biology and its implication on cardiotoxicity and vascular complications thus far have failed to highlight the significance of these factors. Factoring in these integral parts of the endothelium will enhance our understanding of the contribution of the endothelium to radiation biology. Without such information, the current approaches to studying radiation-induced injury to the endothelium and its consequences in health and disease are limited. PMID- 27387859 TI - Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015. AB - After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. PMID- 27387861 TI - A Molecular Profile of the Endothelial Cell Response to Ionizing Radiation. AB - Ionizing radiation exposure can cause acute radiation sickness (ARS) by damaging the hematopoietic compartment. Radiation damages quiescent hematopoietic stem cells (HSCs) and proliferating hematopoietic cells, resulting in neutropenia, thrombocytopenia and increased risk for long-term hematopoietic dysfunction and myelodysplasia. While some aspects of the hematopoietic response to radiation injury are intrinsic to hematopoietic cells, the recovery of the HSC pool and overall hematopoiesis is also dependent on signals from bone marrow endothelial cells (BM ECs) within the HSC vascular niche. The precise mechanisms through which BM ECs regulate HSC regeneration remain unclear. Characterization of the altered EC gene expression that occurs in response to radiation could provide a roadmap to the discovery of EC-derived mechanisms that regulate hematopoietic regeneration. Here, we show that 5 Gy total-body irradiation substantially alters the expression of numerous genes in BM ECs within 24 h and this molecular response largely resolves by day 14 postirradiation. Several unique and nonannotated genes, which encode secreted proteins were upregulated and downregulated in ECs in response to radiation. These results highlight the complexity of the molecular response of BM ECs to ionizing radiation and identify several candidate mechanisms that should be prioritized for functional analysis in models of hematopoietic injury and regeneration. PMID- 27387863 TI - Bolide impact triggered the Late Triassic extinction event in equatorial Panthalassa. AB - Extinctions within major pelagic groups (e.g., radiolarians and conodonts) occurred in a stepwise fashion during the last 15 Myr of the Triassic. Although a marked decline in the diversity of pelagic faunas began at the end of the middle Norian, the cause of the middle Norian extinction is uncertain. Here we show a possible link between the end-middle Norian radiolarian extinction and a bolide impact. Two palaeoenvironmental events occurred during the initial phase of the radiolarian extinction interval: (1) a post-impact shutdown of primary and biogenic silica production within a time span of 10(4)-10(5) yr, and (2) a sustained reduction in the sinking flux of radiolarian silica for ~0.3 Myr after the impact. The catastrophic collapse of the pelagic ecosystem at this time was probably the dominant factor responsible for the end-middle Norian conodont extinction. PMID- 27387862 TI - Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases. AB - Exposure to ionizing radiation induces not only apoptosis but also senescence. While the role of endothelial cell apoptosis in mediating radiation-induced acute tissue injury has been extensively studied, little is known about the role of endothelial cell senescence in the pathogenesis of radiation-induced late effects. Senescent endothelial cells exhibit decreased production of nitric oxide and expression of thrombomodulin, increased expression of adhesion molecules, elevated production of reactive oxygen species and inflammatory cytokines and an inability to proliferate and form capillary-like structures in vitro. These findings suggest that endothelial cell senescence can lead to endothelial dysfunction by dysregulation of vasodilation and hemostasis, induction of oxidative stress and inflammation and inhibition of angiogenesis, which can potentially contribute to radiation-induced late effects such as cardiovascular diseases (CVDs). In this article, we discuss the mechanisms by which radiation induces endothelial cell senescence, the roles of endothelial cell senescence in radiation-induced CVDs and potential strategies to prevent, mitigate and treat radiation-induced CVDs by targeting senescent endothelial cells. PMID- 27387865 TI - [Not Available]. PMID- 27387866 TI - Special Section Guest Editorial: Tissue and Blood Optical Clearing for Biomedical Applications. PMID- 27387864 TI - Importance of IVUS in the treatment with retrograde approach of a long in-stent chronic total occlusion of ostial right coronary artery: A case report. AB - A 43year-old male, with a long history of coronary artery disease, was electively admitted to our institution because of dyspnea for moderate physical efforts (NYHA 2) related to an in-stent chronic total occlusion of ostial RCA and with demonstration of a significant area of inducible myocardial ischemia at stress echocardiography. After a gentle attempt of antegrade approach, the in-stent CTO of ostial RCA was successfully reopened with a retrograde approach using a knuckle technique. After IVUS evaluation which showed that the course of the retrograde guidewire was mostly within the stent strut circumference with the exception of the ostial RCA where the guidewire past between the stent and the vessel wall, implantation of 4 drug-eluting stent was performed from mid to ostial RCA with a good final result. The hospital stay was uneventful. At 6months clinical follow-up the patient was in good clinical condition. We discuss some aspects related to procedural technique, the importance of IVUS evaluation in the treatment of this patient. PMID- 27387867 TI - Enhanced anti-cancer activities of a gold(III) pyrrolidinedithiocarbamato complex incorporated in a biodegradable metal-organic framework. AB - An anti-cancer active gold(III) pyrrolidinedithiocarbamato complex [(PDTC)AuIIICl2] (1) has been synthesized and characterized by means of X-ray crystallography. Compared to the pyrrolidinedithiocarbamate ligand itself, this gold(III) complex displays an up to 33-fold higher anti-cancer potency towards a panel of cancer cell lines including the cisplatin-resistant ovarian carcinoma cell line (A2780cis). As demonstrated by a set of Transwell(r) assay-based cytotoxicity experiments, incorporating this gold(III) complex in a zinc-based biodegradable metal-organic framework (MOF) displays a significant enhancement in anti-cancer activity towards A2780cis than the gold(III) complex alone. PMID- 27387868 TI - MTHFR c.677C>T is a risk factor for non-syndromic cleft lip with or without cleft palate in Chile. AB - OBJECTIVE: The functional variant within the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene c.677C>T, producing alterations in folate metabolism, has been associated with the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). We assessed this association in a Chilean population using a combined analysis of case-control and case-parent trio samples. SUBJECTS AND METHODS: Samples of 165 cases and 291 controls and 121 case-parent trios (sharing the cases) were genotyped. Odds ratio (OR) was estimated for case-control (allele and genotype frequency differences), and this result was confirmed by allele transmission distortion in trios. Due to that these samples are not independent, a combined OR was also computed. Maternal genotype effect was additionally evaluated based on a log-linear method. RESULTS: Borderline but not significant OR (1.28; CI 0.97-1.69) was observed for risk allele (T) in the case-control sample. However, triad sample showed a significant association (OR 1.56: CI 1.09 2.25) which was confirmed by the combined OR (1.37; CI 1.11-1.71). Maternal genotype has been also associated with the phenotype (P = 0.002). CONCLUSIONS: In contrast to previous reports considering Chilean subjects, our results demonstrated that the offspring and maternal genotypes for MTHFR c.677C>T variant are strongly associated with NSCL/P in this Chilean population. PMID- 27387869 TI - Mother's Gut Arms Offspring. PMID- 27387870 TI - The Will of the Human Embryo. PMID- 27387871 TI - Lizard tail skeletal regeneration combines aspects of fracture healing and blastema-based regeneration. AB - Lizards are amniotes with the remarkable ability to regenerate amputated tails. The early regenerated lizard tail forms a blastema, and the regenerated skeleton consists of a cartilage tube (CT) surrounding the regenerated spinal cord. The proximal, but not distal, CT undergoes hypertrophy and ossifies. We hypothesized that differences in cell sources and signaling account for divergent cartilage development between proximal and distal CT regions. Exogenous spinal cord implants induced ectopic CT formation in lizard (Anolis carolinensis) blastemas. Regenerated spinal cords expressed Shh, and cyclopamine inhibited CT induction. Blastemas containing vertebrae with intact spinal cords formed CTs with proximal hypertrophic regions and distal non-hypertrophic regions, whereas removal of spinal cords resulted in formation of proximal CT areas only. In fate-mapping studies, FITC-labeled vertebra periosteal cells were detected in proximal, but not distal, CT areas. Conversely, FITC-labeled blastema cells were restricted to distal CT regions. Proximal cartilage formation was inhibited by removal of periosteum and could be recapitulated in vitro by periosteal cells treated with Ihh and BMP-2. These findings suggest that proximal CTs are directly derived from vertebra periosteal cells in response to BMP and Ihh signaling, whereas distal CTs form from blastema cells in response to Shh signals from regenerated spinal cords. PMID- 27387873 TI - Subliminal stimulation and somatosensory signal detection. AB - Only a small fraction of sensory signals is consciously perceived. The brain's perceptual systems may include mechanisms of feedforward inhibition that protect the cortex from subliminal noise, thus reserving cortical capacity and conscious awareness for significant stimuli. Here we provide a new view of these mechanisms based on signal detection theory, and gain control. We demonstrated that subliminal somatosensory stimulation decreased sensitivity for the detection of a subsequent somatosensory input, largely due to increased false alarm rates. By delivering the subliminal somatosensory stimulus and the to-be-detected somatosensory stimulus to different digits of the same hand, we show that this effect spreads across the sensory surface. In addition, subliminal somatosensory stimulation tended to produce an increased probability of responding "yes", whether the somatosensory stimulus was present or not. Our results suggest that subliminal stimuli temporarily reduce input gain, avoiding excessive responses to further small inputs. This gain control may be automatic, and may precede discriminative classification of inputs into signals or noise. Crucially, we found that subliminal inputs influenced false alarm rates only on blocks where the to-be-detected stimuli were present, and not on pre-test control blocks where they were absent. Participants appeared to adjust their perceptual criterion according to a statistical distribution of stimuli in the current context, with the presence of supraliminal stimuli having an important role in the criterion setting process. These findings clarify the cognitive mechanisms that reserve conscious perception for salient and important signals. PMID- 27387872 TI - Multiscale quantification of morphodynamics: MorphoLeaf software for 2D shape analysis. AB - A major challenge in morphometrics is to analyse complex biological shapes formed by structures at different scales. Leaves exemplify this challenge as they combine differences in their overall shape with smaller shape variations at their margin, leading to lobes or teeth. Current methods based on contour or on landmark analysis are successful in quantifying either overall leaf shape or leaf margin dissection, but fail in combining the two. Here, we present a comprehensive strategy and its associated freely available platform for the quantitative, multiscale analysis of the morphology of leaves with different architectures. For this, biologically relevant landmarks are automatically extracted and hierarchised, and used to guide the reconstruction of accurate average contours that properly represent both global and local features. Using this method, we establish a quantitative framework of the developmental trajectory of Arabidopsis leaves of different ranks and retrace the origin of leaf heteroblasty. When applied to different mutant forms, our method can contribute to a better understanding of gene function, as we show here for the role of CUC2 during Arabidopsis leaf serration. Finally, we illustrate the wider applicability of our tool by analysing hand morphometrics. PMID- 27387874 TI - Involvement of Spearman's g in conceptualisation versus execution of complex tasks. AB - Strong correlations between measures of fluid intelligence (or Spearman's g) and working memory are widely reported in the literature, but there is considerable controversy concerning the nature of underlying mechanisms driving this relationship. In the four experiments presented here we consider the role of response conflict and task complexity in the context of real-time task execution demands (Experiments 1-3) and also address recent evidence that g confers an advantage at the level of task conceptualisation rather than (or in addition to) task execution (Experiment 4). We observed increased sensitivity of measured fluid intelligence to task performance in the presence (vs. the absence) of response conflict, and this relationship remained when task complexity was reduced. Performance-g correlations were also observed in the absence of response conflict, but only in the context of high task complexity. Further, we present evidence that differences in conceptualisation or 'modelling' of task instructions prior to execution had an important mediating effect on observed correlations, but only when the task encompassed a strong element of response inhibition. Our results suggest that individual differences in ability reflect, in large part, variability in the efficiency with which the relational complexity of task constraints are held in mind. It follows that fluid intelligence may support successful task execution through the construction of effective action plans via optimal allocation of limited resources. PMID- 27387875 TI - Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort. AB - OBJECTIVES: To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. METHODS: A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. RESULTS: Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. CONCLUSION: Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. KEY POINTS: * Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. * Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. * There is a correlation between risk factors and causes of recurrence. * Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe. PMID- 27387876 TI - High-resolution intracranial vessel wall MRI in an elderly asymptomatic population: comparison of 3T and 7T. AB - OBJECTIVES: Several intracranial vessel wall sequences have been described in recent literature, with either 3-T or 7-T magnetic resonance imaging (MRI). In the current study, we compared 3-T and 7-T MRI in visualising both the intracranial arterial vessel wall and vessel wall lesions. METHODS: Twenty-one elderly asymptomatic volunteers were scanned by 3-T and 7-T MRI with an intracranial vessel wall sequence, both before and after contrast administration. Two raters scored image quality, and presence and characteristics of vessel wall lesions. RESULTS: Vessel wall visibility was equal or significantly better at 7 T for the studied arterial segments, even though there were more artefacts hampering assessment. The better visualisation of the vessel wall at 7 T was most prominent in the proximal anterior cerebral circulation and the posterior cerebral artery. In the studied elderly asymptomatic population, 48 vessel-wall lesions were identified at 3 T, of which 7 showed enhancement. At 7 T, 79 lesions were identified, of which 29 showed enhancement. Seventy-one percent of all 3-T lesions and 59 % of all 7-T lesions were also seen at the other field strength. CONCLUSIONS: Despite the large variability in detected lesions at both field strengths, we believe 7-T MRI has the highest potential to identify the total burden of intracranial vessel wall lesions. KEY POINTS: * Intracranial vessel wall visibility was equal or significantly better at 7-T MRI * Most vessel wall lesions in the cerebral arteries were found at 7-T MRI * Many intracranial vessel wall lesions showed enhancement after contrast administration * Large variability in detected intracranial vessel wall lesions at both field strengths * Seven tesla MRI has the highest potential to identify total burden of intracranial atherosclerosis. PMID- 27387877 TI - Increased arterial pulsatility and progression of single subcortical infarction. AB - OBJECTIVE: We investigated the association of clinical, laboratory, sonographic and imaging parameters, in the progression of single subcortical infarctions. METHODS: Consecutive 169 patients with lacunar (n = 89) and striatocapsular infarctions (n = 80) in the middle cerebral artery (MCA) territory with nonstenotic MCAs were recruited and examined for stroke progression. The pulsatility index (PI) was measured by transcranial Doppler from ipsilateral M1. RESULTS: The striatocapsular infarction group exhibited more stroke progression. The patients with progressive lacunar infarctions had more diabetes, higher HbA1c levels, and higher initial National Institutes of Health Stroke Scale (NIHSS) scores, and the patients with progressive striatocapsular infarctions had more hypertension, higher cholesterol levels, and higher NIHSS scores. The MCA PI was higher in the lacunar infarction patients with progression (0.99 +/- 0.19 vs. 0.90 +/- 0.14, p = 0.048), while the striatocapsular infarction patients did not differ according to progression. From a multivariate analysis, higher MCA PI were independently associated with lacunar infarction progression (by 0.1 increase, OR 1.51; 95 % CI 1.06-2.15; p = 0.024). CONCLUSIONS: Higher pulsatility was associated with progression in lacunar infarction. PI measured by transcranial Doppler sonography might reflect downstream arterial resistance and vascular/paravascular perfusion status and be a possible indicator of stroke progression. KEY POINTS: * Higher pulsatility index was observed in progression group of lacunar infarction patients. * Higher pulsatility index seemed to be associated with progression in lacunar infarction patients. * Differences in the factors associated with stroke progression suggest different underlying pathophysiologies. PMID- 27387879 TI - All in one: Researchers create combination drugs for diabetes and obesity. PMID- 27387878 TI - Vouching for access. PMID- 27387880 TI - Metabolism in mind: New insights into the 'gut-brain axis' spur commercial efforts to target it. PMID- 27387881 TI - A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation. PMID- 27387882 TI - Promiscuous mechanisms underlie the antitumor effects of thalidomide analogs. PMID- 27387883 TI - Independence of epigenetic and genetic diversity in AML. PMID- 27387884 TI - Targeting the brain as a cure for type 2 diabetes. PMID- 27387885 TI - Follicular T helper cells: hotspots for HIV-1 persistence. PMID- 27387888 TI - Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome. AB - PURPOSE: In the present study, we reported two cases of TS with mosaic ring X chromosome showing common clinical characteristics of TS like growth retardation and ovarian dysfunction. The purpose of the present study was to cytogenetically characterize both cases. METHODS: Whole blood culture and G-banding were performed for karyotyping the cases following standard protocol. Origin of the ring chromosome and degree of mosaicism were further determined by fluorescence in situ hybridization (FISH). Breakpoints and loss of genetic material in formation of different ring X chromosomes r (X) in cases were determined with the help of cytogenetic microarray. RESULTS: Cases 1 and 2 with ring chromosome were cytogenetically characterized as 45, X [114]/46Xr (X) (p22.11q21.32) [116] and 45, X [170]/46, Xr (X) (p22.2q21.33) [92], respectively. Sizes of these ring X chromosomes were found to be ~75 and ~95 Mb in cases 1 and 2, respectively, using visual estimation as part of cytogenetic observation. In both cases, we observed breakpoints on Xq chromosome were within relatively narrow region between Xq21.33 and Xq22.1 compared to regions in previously reported cases associated with ovarian dysgenesis. CONCLUSIONS: Our observation agrees with the fact that despite of large heterogeneity, severity of the cases with intact X-inactive specific transcript (XIST) is dependent on degree of mosaicism and extent of Xq deletion having crucial genes involved directly or indirectly in various physiological involving ovarian cyclicity. PMID- 27387889 TI - Electronic witness system in IVF-patients perspective. AB - OBJECTIVE: The objective of this study is to evaluate patient concerns about in vitro fertilization (IVF) errors and electronic witness systems (EWS) satisfaction. DESIGN: The design of this study is a prospective single-center cohort study. SETTING: The setting of this study was located in the private IVF center. PATIENT(S): Four hundred eight infertile patients attending an IVF cycle at a GENERA center in Italy were equipped with an EWS. INTERVENTION(S): Although generally recognized as a very rare event in IVF, biological sample mix-up has been reported in the literature. For this reason, some IVF laboratories have introduced EWS with the aim to further reduce the risk of error during biological samples handling. Participating patients received a questionnaire developed through a Likert scale ranging from 1 to 6. MAIN OUTCOMES MEASURE(S): Patient concerns about sample mix-up without and with an EWS were assessed. RESULT(S): 90.4 % of patients expressed significant concerns relating to sample mix-up. The EWS reduced these concerns in 92.1 % of patients, 97.1 % of which were particularly satisfied with the electronic traceability of their gametes and embryos in the IVF laboratory. 97.1 % of patients felt highly comfortable with an IVF center equipped with an EWS. Female patients had a significantly higher appreciation of the EWS when compared to their male partners (p = 0.029). A significant mix-up event occurred in an Italian hospital during the study and patient's satisfaction increased significantly towards the use of the EWS after the event (p = 0.032). CONCLUSION(S): EWS, by sensibly reducing the risk for sample mix-up in IVF cycles, has been proved to be a trusted strategy from patient's perspective. PMID- 27387886 TI - The microbiome in early life: implications for health outcomes. AB - Recent studies have characterized how host genetics, prenatal environment and delivery mode can shape the newborn microbiome at birth. Following this, postnatal factors, such as antibiotic treatment, diet or environmental exposure, further modulate the development of the infant's microbiome and immune system, and exposure to a variety of microbial organisms during early life has long been hypothesized to exert a protective effect in the newborn. Furthermore, epidemiological studies have shown that factors that alter bacterial communities in infants during childhood increase the risk for several diseases, highlighting the importance of understanding early-life microbiome composition. In this review, we describe how prenatal and postnatal factors shape the development of both the microbiome and the immune system. We also discuss the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations. PMID- 27387890 TI - Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats. AB - Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O2), one kept at normothermia (HN) (37 degrees C) and the other under deep hypothermia (HH) (central body temperature of 21-22 degrees C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia. PMID- 27387891 TI - A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients. AB - Myasthenia gravis (MG) is a T-cell dependent autoimmune disorder of the neuromuscular junction, characterised by muscle weakness and fatigability. Autoimmunity is thought to initiate in the thymus of acetylcholine receptor (AChR)-positive MG patients; however, the molecular mechanisms linking intra thymic MG pathogenesis with autoreactivity via the circulation to the muscle target organ are poorly understood. Using whole-transcriptome sequencing, we compared the transcriptional profile of peripheral blood mononuclear cells from AChR-early onset MG (AChR-EOMG) patients with healthy controls: 178 coding transcripts and 229 long non-coding RNAs, including 11 pre-miRNAs, were differentially expressed. Among the 178 coding transcripts, 128 were annotated of which 17% were associated with the 'infectious disease' functional category and 46% with 'inflammatory disease' and 'inflammatory response-associated' categories. Validation of selected transcripts by qPCR indicated that of the infectious disease-related transcripts, ETF1, NFKB2, PLK3, and PPP1R15A were upregulated, whereas CLC and IL4 were downregulated in AChR-EOMG patients; in the 'inflammatory' categories, ABCA1, FUS, and RELB were upregulated, suggesting a contribution of these molecules to immunological dysfunctions in MG. Data selection and validation were also based on predicted microRNA-mRNA interactions. We found that miR-612, miR-3654, and miR-3651 were increased, whereas miR-612 putative AKAp12 and HRH4 targets and the miR-3651-putative CRISP3 target were downregulated in AChR-EOMG, also suggesting altered immunoregulation. Our findings reveal a novel peripheral molecular signature in AChR-EOMG, reflecting a critical involvement of inflammatory- and infectious disease-related immune responses in disease pathogenesis. PMID- 27387892 TI - Use of Palliative Care in Patients With End-Stage COPD and Receiving Home Oxygen: National Trends and Barriers to Care in the United States. AB - BACKGROUND: To investigate the use of palliative care (PC) in patients with end stage COPD receiving home oxygen hospitalized for an exacerbation. METHODS: A retrospective nationwide cohort analysis was performed, using the Nationwide Inpatient Sample. All patients >= 18 years of age with a diagnosis of COPD, receiving home oxygen, and admitted for an exacerbation were included. RESULTS: A total of 55,208,382 hospitalizations from the 2006-2012 Nationwide Inpatient Sample were examined. There were 181,689 patients with COPD, receiving home oxygen, and admitted for an exacerbation; 3,145 patients (1.7%) also had a PC contact. There was a 4.5-fold relative increase in PC referral from 2006 (0.45%) to 2012 (2.56%) (P < .01). Patients receiving PC consultations compared with those who did not were older (75.0 years [SD 10.9] vs 70.6 years [SD 9.7]; P < .01), had longer hospitalizations (4.9 days [interquartile range, 2.6-8.2] vs 3.5 days [interquartile range, 2.1-5.6]), and more likely to die in hospital (32.1% vs 1.5%; P < .01). Race was significantly associated with referral to palliative care, with white patients referred more often than minorities (P < .01). Factors associated with PC referral included age (OR, 1.03; 95% CI, 1.02-1.04; P < .01), metastatic cancer (OR, 2.40; 95% CI, 2.02-2.87; P < .01), nonmetastatic cancer (OR, 2.75; 95% CI, 2.43-3.11; P < .01), invasive mechanical ventilation (OR, 4.89; 95% CI, 4.31-5.55; P < .01), noninvasive mechanical ventilation (OR, 2.84; 95% CI, 2.58-3.12; P < .01), and Do Not Resuscitate status (OR, 7.95; 95% CI, 7.29-8.67; P < .01). CONCLUSIONS: The use of PC increased dramatically during the study period; however, PC contact occurs only in a minority of patients with end stage COPD admitted with an exacerbation. PMID- 27387893 TI - Technologies, technical steps, and early postoperative results of transanal TME. AB - INTRODUCTION: First described in 1982, TME overcomes most of the concerns regarding adequate local control after anterior rectal resection. TME requires close sharp dissection along the so-called Heald's plane down to the levators, with distal dissection often cumbersome. In recent years, Transanal TME was introduced with the aim to improve distal rectal dissection and quality of mesorectal excision. MATERIAL AND METHODS: A prospective, non-randomized study, started in 2013, is currently ongoing in two Italian Centers. Study objectives were assessing the safety of TaTME and TME quality. TaTME technique and technologies as performed in these centers and cumulative results at <=30 postoperative days of the first 102 patients are reported. RESULTS: Early postoperative morbidity and mortality rates were 33.3% (34 pts, 16 Clavien-Dindo I + II and 18 Clavien-Dindo III + IV + V), and 1.96% (two deaths), respectively. The quality of mesorectal excision according to Quirke was: complete in 97.1% and nearly complete in 2.9% of the cases. CONCLUSIONS: The results confirm the effectiveness of TaTME, especially regarding the quality of the mesorectal dissection. Open questions regarding standardization, anatomical landmarks, indications, morbidity (with special regard to local infection and sepsis), learning curve and oncological outcomes require further answers from larger studies and RCTs before definitive validation of this procedure. . PMID- 27387894 TI - Bioconversion of AHX to AOH by resting cells of Burkholderia contaminans CH-1. AB - Fairy rings are zones of stimulated grass growth owing to the interaction between a fungus and a plant. We previously reported the discovery of two novel plant growth regulating compounds related to forming fairy rings, 2-azahypoxanthine (AHX) and 2-aza-8-oxohypoxanthine (AOH). In this study, a bacterial strain CH-1 was isolated from an airborne-contaminated nutrient medium containing AHX. The strain converted AHX to AOH and identified as Burkholderia contaminans based on the gene sequence of its 16S rDNA. The quantitative production of AOH by resting cells of the strain was achieved. Among seven Burkholderia species, two bacteria and two yeasts tested, B. contaminans CH-1 showed the highest rate of conversion of AHX to AOH. By batch system, up to 10.6 mmol AHX was converted to AOH using the resting cells. The yield of this process reached at 91%. PMID- 27387896 TI - Total replacement of corn by mesquite pod meal considering nutritional value, performance, feeding behavior, nitrogen balance, and microbial protein synthesis of Holstein-Zebu crossbred dairy steers. AB - The objective of the present study to assess the effects of mesquite pod addition replacing corn (0, 250, 500, 750, and 1000 g/kg in the dry matter basis) on nutrient intake, animal performance, feeding behavior, nutrient digestibility, nitrogen balance, and microbial protein synthesis. Twenty-five Holstein-Zebu crossbred dairy steers at 219 +/- 22 kg initial body weight and 18 months of age were used. The experiment lasted 84 days, divided into three periods of 28 days. A completely randomized design was used, and data were submitted to analysis using PROC GLM for analysis of variance and PROC REG for regression analysis using the software Statistical Analysis Systems version 9.1. Experimental diets were composed of Tifton 85 hay, soybean meal, ground corn, mesquite pod meal, and mineral salt. Samples of food offered were collected during the last 3 days of each period, and the leftovers were collected daily, with samples bulked per week. At the end of each 28-day period, the remaining animals were weighed to determine total weight gain and average daily gain. The assessment of behavioral patterns was performed through instantaneous scans in 5-min intervals for three consecutive 12-h days. A single urine sample from each animal was collected on the last day of each collection period at about 4 h after the first feeding. The replacement of corn by mesquite pod meal did not significantly influence treatments regarding nutrients intake, animal performance, and feeding behavior. Retained and consumed nitrogen ratio did not statistically differ between replacement levels. Likewise, there were no statistical differences regarding microbial protein synthesis and efficiency between replacement levels. Mesquite pod meal can be used in Holstein-Zebu crossbred dairy steers' diet with total corn replacement. PMID- 27387895 TI - Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats. AB - RATIONALE: Inflammation plays a key role in the pathogenesis of major depressive disorder (MDD) for a subset of depressed individuals. One of the possible routes by which cytokines can induce depressive symptoms is by promoting the dysregulation of hypothalamic-pituitary-adrenal (HPA) axis via altering glucocorticoid receptor (GR) function. OBJECTIVES: We investigated the mechanisms that finely tune the GR functioning upon lipopolysaccharide (LPS), i.e., subcellular localization of the GR, the levels of its co-chaperones FK506 binding protein 52 (FKBP4) and FK506 binding protein 51 (FKBP5), the receptor phosphorylation status along with its upstream kinases, as well as mRNA levels of GR-regulated genes in the prefrontal cortex (PFC) of male and female Wistar rats. RESULTS: We found that upon LPS treatment, animals of both sexes exhibited depressive-like behavior and elevated serum corticosterone. However, the nuclear translocation of the GR and both FKBPs was found only in males, together with elevated phosphorylation of the GR at serine 232 and 246 and the activation and nuclear translocation of all analyzed kinases. This activation of the GR in males was paralleled with altered expression of GR-related genes, particularly PTGS2 and BDNF. CONCLUSION: Our data suggest that LPS treatment produced alterations in the mechanisms that control the GR nuclear translocation in the PFC of males, and that these mechanisms may contribute to the sex-specific dysfunction of GR related neurotrophic and neuroinflammatory processes in inflammation-associated depression. PMID- 27387897 TI - Inflammation and macrophage polarization in cutaneous melanoma: Histopathological and immunohistochemical study. AB - Tumor-associated macrophages (TAMs) are considered to affect tumor growth and progression. Macrophages can be classified into two states of polarized activation, namely classically activated M1 macrophages and alternatively activated M2 macrophages. The dynamic balance between TAMs and tumor cells has an important impact on tumor homeostasis and progression. The aim of this study was to characterize the phenotype of TAMs present in different subtypes of superficial spreading cutaneous melanoma and their relationship with the lymphocytic infiltrate in order to identify new histopathological tools for melanoma prognosis and suitable targets for melanoma therapy. We selected four groups of patients with malignant melanoma in order to analyze the profile of polarized macrophage activation using immunohistochemical methods. Histopathological analysis showed that the macrophage polarization state appears to be more related to the lymphocytic infiltrate than to the thickness of the lesions. Further studies are necessary to increase understanding of the immunopathological dynamic of melanoma that may be modulated by future targeted immunotherapies. PMID- 27387899 TI - Additional double-wall roof in single-wall, closed, convective incubators: Impact on body heat loss from premature infants and optimal adjustment of the incubator air temperature. AB - Radiant heat loss is high in low-birth-weight (LBW) neonates. Double-wall or single-wall incubators with an additional double-wall roof panel that can be removed during phototherapy are used to reduce Radiant heat loss. There are no data on how the incubators should be used when this second roof panel is removed. The aim of the study was to assess the heat exchanges in LBW neonates in a single wall incubator with and without an additional roof panel. To determine the optimal thermoneutral incubator air temperature. Influence of the additional double-wall roof was assessed by using a thermal mannequin simulating a LBW neonate. Then, we calculated the optimal incubator air temperature from a cohort of human LBW neonate in the absence of the additional roof panel. Twenty-three LBW neonates (birth weight: 750-1800g; gestational age: 28-32 weeks) were included. With the additional roof panel, R was lower but convective and evaporative skin heat losses were greater. This difference can be overcome by increasing the incubator air temperature by 0.15-0.20 degrees C. The benefit of an additional roof panel was cancelled out by greater body heat losses through other routes. Understanding the heat transfers between the neonate and the environment is essential for optimizing incubators. PMID- 27387898 TI - Biomarkers of brain injury following an American football game: A pilot study. AB - The goals of this study were to determine if the biomarkers of head injury, NSE and S100B, increased in serum following an American football game. Serum creatine kinase (CK) and cortisol levels were also measured to determine muscle damage and stress caused by the football game. NSE, S100B, CK, and cortisol were measured in the serum of 17 football players before and after a collegiate junior varsity football game. No head injuries were reported by the players, athletic training staff, or coaches yet both NSE (Pre-game: 7.0 MUg*L-1 +/- 2.2 versus Post-game: 13.1 MUg*L-1 +/- 7.0, P <0.001) and S100B (Pre-game: 0.013 MUg*L-1 +/- 0.012 versus Post-game: 0.069 MUg*L-1 +/- 0.036, P <0.001) increased significantly. Neither CK (Pre-game: 90.5 U*L-1 +/- 41.9 versus Post-game: 120.2 U*L-1 +/- 62.7, P = 0.116) nor cortisol (Pre-game: 369.2 nmoles*L-1 +/- 159.8 versus Post-game: 353.0 nmoles*L-1 +/- 170.5, P = 0.349) increased significantly following the football game. There was little correlation found between S100B and body mass (R2 = 0.029) or CK (R2 = 0.352) levels. Although serum NSE and S100B increase as a result of playing in an American football game, the values are similar to or lower than levels found following competition in other contact and non-contact sports. Furthermore, the lack of correlation between S100B and body mass or CK indicates that S100B increases independent of body mass or muscle injury. PMID- 27387900 TI - Experimental determination of the emissivity of bone. AB - Cutting and drilling operations in bone are involved in many orthopedic and otolaryngological surgeries. The temperature elevation of these procedures is potentially harmful to bone and soft tissue cells. The research on this topic aims therefore at minimizing temperature elevation and finding optimal process parameters. Experimental studies are mostly carried out on ex vivo setups using bovine bone material. For temperature measurements, either thermocouples or infrared cameras are used. Infrared cameras have potential advantages, but the emissivity value of the material has to be known. Literature values are scattered and vary within a wide range. An experimental study was carried out to quantify the emissivity using freshly frozen bovine and human bone, as well as human bone samples which were either fixed with Formalin or Thiel solution. Additionally, different surface finishes were used and emissivity was evaluated at different temperatures. The mean emissivity of bone was determined to be E=0.96+/-0.01 for temperature elevations up to 60 degrees C. A slightly higher value of E=0.97+/ 0.01 was found for temperatures around 80 degrees C. No significant differences for human or bovine bone samples, preparation or fixation techniques were found. PMID- 27387901 TI - Concurrent validity of the Microsoft Kinect for Windows v2 for measuring spatiotemporal gait parameters. AB - This paper presents a study to evaluate the concurrent validity of the Microsoft Kinect for Windows v2 for measuring the spatiotemporal parameters of gait. Twenty healthy adults performed several sequences of walks across a GAITRite mat under three different conditions: usual pace, fast pace, and dual task. Each walking sequence was simultaneously captured with two Kinect for Windows v2 and the GAITRite system. An automated algorithm was employed to extract various spatiotemporal features including stance time, step length, step time and gait velocity from the recorded Kinect v2 sequences. Accuracy in terms of reliability, concurrent validity and limits of agreement was examined for each gait feature under different walking conditions. The 95% Bland-Altman limits of agreement were narrow enough for the Kinect v2 to be a valid tool for measuring all reported spatiotemporal parameters of gait in all three conditions. An excellent intraclass correlation coefficient (ICC2, 1) ranging from 0.9 to 0.98 was observed for all gait measures across different walking conditions. The inter trial reliability of all gait parameters were shown to be strong for all walking types (ICC3, 1 > 0.73). The results of this study suggest that the Kinect for Windows v2 has the capacity to measure selected spatiotemporal gait parameters for healthy adults. PMID- 27387903 TI - Dynamic material characterization of the human heel pad based on in vivo experimental tests and numerical analysis. AB - A numerical-experimental, proof-of-concept approach is described to characterize the mechanical material behavior of the human heel pad under impact conditions similar to a heel strike while running. A 3D finite-element model of the right foot of a healthy female subject was generated using magnetic resonance imaging. Based on quasi-static experimental testing of the subject's heel pad, force displacement data was obtained. Using this experimental data as well as a numerical optimization algorithm, an inverse finite-element analysis and the 3D model, heel pad hyperelastic (long-term) material parameters were determined. Applying the same methodology, based on the dynamic experimental data from the impact test and obtained long-term parameters, linear viscoelastic parameters were established with a Prony series. Model validation was performed employing quasi-static and dynamic force-displacement data. Coefficients of determination when comparing model to experimental data during quasi-static and dynamic (initial velocity: 1480mm/s) procedure were R(2) = 0.999 and R(2) = 0.990, respectively. Knowledge of these heel pad material parameters enables realistic numerical analysis to evaluate internal stress and strain in the heel pad during different quasi-static or dynamic load conditions. PMID- 27387902 TI - Accuracy of model-based tracking of knee kinematics and cartilage contact measured by dynamic volumetric MRI. AB - The purpose of this study was to determine the accuracy of knee kinematics and cartilage contact measured by volumetric dynamic MRI. A motor-actuated phantom drove femoral and tibial bone segments through cyclic 3D motion patterns. Volumetric images were continuously acquired using a 3D radially undersampled cine spoiled gradient echo sequence (SPGR-VIPR). Image data was binned based on position measured via a MRI-compatible rotary encoder. High-resolution static images were segmented to create bone models. Model-based tracking was performed by optimally registering the bone models to the volumetric images at each frame of the SPGR-VIPR series. 3D tibiofemoral translations and orientations were reconstructed, and compared to kinematics obtained by tracking fiducial markers. Imaging was repeated on a healthy subject who performed cyclic knee flexion extension. Cartilage contact for the subject was assessed by measuring the overlap between articular cartilage surfaces. Model-based tracking was able to track tibiofemoral angles and translations with precisions less than 0.8 degrees and 0.5mm. These precisions resulted in an uncertainty of less than 0.5mm in cartilage contact location. Dynamic SPGR-VIPR imaging can accurately assess in vivo knee kinematics and cartilage contact during voluntary knee motion performed in a MRI scanner. This technology could facilitate the quantitative investigation of links between joint mechanics and the development of osteoarthritis. PMID- 27387904 TI - In vitro osteocytic microdamage and viability quantification using a microloading platform. AB - Bone remodeling is a process in which bone is resorbed by osteoclasts and formed by osteoblasts. This is normally a paired process, although it can be disrupted by changes in mechanical load. One theory is that osteocytes play a key role in the cellular regulation of this process. Mechanotransduction studies, which investigate how cells convert mechanical stimuli into biophysical effects and cellular activity, offer one way to investigate this theory. Mechanotransduction work is commonly done by applying an isolated mechanical load to cells grown in vitro, and quantifying the response. While in vitro work does not fully replicate the natural environment, it does allow the study of isolated factors. In this study, a mechanical loading platform was designed, fabricated, and characterized for bone mechanotransduction studies. This platform was designed to tent cell seeded substrates from below, loading using out of plane distension. This introduced a nonuniform strain profile, enabling the study of cells cultured under identical conditions and variable strains as a function of substrate location. An alphanumerically gridded polydimethylsiloxane well substrate was designed and fabricated for cellular loading experiments. Following initial characterization, a study was run to quantify the cellular activity of osteocyte like MLO-Y4 cells as a function of strain field. The results indicated that regions with lower strains led to an increase in cellular activity while higher strains led to a reduction in cellular activity. This demonstrated that cells could be exposed to mechanically-induced microdamage using the microloading platform. PMID- 27387905 TI - Derivation of flow related risk indices for stenosed left anterior descending coronary arteries with the use of computer simulations. AB - The geometry of the coronary vessel network is believed to play a decisive role in the initiation, progression and outcome of coronary artery disease (CAD) and the occurrence of acute coronary syndromes (ACS). It also determines the flow field in the coronary artery which can be linked to CAD evolution. In this work geometric 3D models of left anterior descending (LAD) coronary arteries associated with either myocardial infarction (MI) or stable (STA) CAD were constructed. Transient numerical simulations of the flow for each model showed that specific flow patterns develop in different extent in the different groups examined. Recirculation zones, present distal the stenosis in all models, had larger extent and duration in MI cases. For mild stenosis (up to 50%) areas with low time averaged wall shear stress TAWSS (<0.15Pa) as well as areas with high TAWSS (>3Pa) appeared only in MI models; in moderate and severe stenosis (>50%) these areas were present in all models but were significantly larger for MI than STA models. These differentiations were expressed via numerical indices based on TAWSS, oscillating shear index (OSI) and relative residence time (RRT). Additionally we introduced the coagulation activation index (CAI), based on the threshold behaviour of coagulation initiation, which exceeded the suggested threshold only for MI models with intermediate stenosis (up to 50%). These results show that numerical simulations of flow can produce arithmetic indices linked with the risk of CAD complications. PMID- 27387906 TI - An efficient method to capture the impact of total knee replacement on a variety of simulated patient types: A finite element study. AB - Osteoporosis resulting in a reduction in bone stiffness and thinning of the cortex is almost universal in older patients. In this study a novel method to generate computational models of the distal femur which incorporate the effects of ageing and endosteal trabecularisation are presented. Application of this method to pre- and post-knee arthroplasty scenarios is then considered. These computational methods are found to provide a simple yet effective tool for assessing the post-arthroplasty mechanical environment in the knee for different patient types and can help evaluate vulnerability to supracondylar periprosthetic fracture following implantation. Our results show that the stresses in the periprosthetic region increase dramatically with ageing; this is particularly true for higher flexion angles. Stresses in the anterior region of the femoral cortex were also found to increase significantly post-implantation. The most dramatic increases in stresses and strains at these locations were observed in old osteoporotic patients, explaining why this patient group in particular is at greater risk of periprosthetic fractures. PMID- 27387907 TI - Feasibility of freehand ultrasound to measure anatomical features associated with deep tissue injury risk. AB - Deep tissue injuries (DTI) are severe forms of pressure ulcers that start internally and are difficult to diagnose. Magnetic resonance imaging (MRI) is the currently preferred imaging modality to measure anatomical features associated with DTI, but is not a clinically feasible risk assessment tool. B-mode ultrasound (US) is proposed as a practical, alternative technology suitable for bedside or outpatient clinic use. The goal of this research was to confirm US as an imaging modality for acquiring measurements of anatomical features associated with DTI. Tissue thickness measurements using US were reliable (ICC=.948) and highly correlated with MRI measurements (muscle r=.988, p <= .001; adipose r=.894, p <= .001; total r=.919; p <= .001). US measures of muscle tissue thickness were 5.4mm (34.1%) higher than MRI, adipose tissue thickness measures were 1.6mm (11.9%) lower, and total tissue thickness measures were 3.8mm (12.8%) higher. Given the reliability and ability to identify high-risk anatomies, as well as the cost effectiveness and availability, US measurements show promise for use in future development of a patient-specific, bedside, biomechanical risk assessment tool to guide clinicians in appropriate interventions to prevent DTI. PMID- 27387908 TI - Bacterial and fungal symbionts of parasitic Dendroctonus bark beetles. AB - Bark beetles (Curculionidae: Scolytinae) are one of the most species-rich herbivorous insect groups with many shifts in ecology and host-plant use, which may be mediated by their bacterial and fungal symbionts. While symbionts are well studied in economically important, tree-killing species, little is known about parasitic species whose broods develop in living trees. Here, using culture dependent and independent methods, we provide a comprehensive overview of the associated bacteria, yeasts and filamentous fungi of the parasitic Dendroctonus micans, D. punctatus and D. valens, and compare them to those of other tree inhabiting insects. Despite inhabiting different geographical regions and/or host trees, the three species showed similar microbial communities. Enterobacteria were the most prevalent bacteria, in particular Rahnella, Pantoea and Ewingella, in addition to Streptomyces Likewise, the yeasts Candida/Cyberlindnera were the most prominent fungi. All these microorganisms are widespread among tree inhabiting insects with various ecologies, but their high prevalence overall might indicate a beneficial role such as detoxification of tree defenses, diet supplementation or protection against pathogens. As such, our results enable comparisons of symbiont communities of parasitic bark beetles with those of other beetles, and will contribute to our understanding of how microbial symbioses facilitate dietary shifts in insects. PMID- 27387909 TI - Active microorganisms in forest soils differ from the total community yet are shaped by the same environmental factors: the influence of pH and soil moisture. AB - Predicting the impact of environmental change on soil microbial functions requires an understanding of how environmental factors shape microbial composition. Here, we investigated the influence of environmental factors on bacterial and fungal communities across an expanse of northern hardwood forest in Michigan, USA, which spans a 500-km regional climate gradient. We quantified soil microbial community composition using high-throughput DNA sequencing on coextracted rDNA (i.e. total community) and rRNA (i.e. active community). Within both bacteria and fungi, total and active communities were compositionally distinct from one another across the regional gradient (bacteria P = 0.01; fungi P < 0.01). Taxonomically, the active community was a subset of the total community. Compositional differences between total and active communities reflected changes in the relative abundance of dominant taxa. The composition of both the total and active microbial communities varied by site across the gradient (P < 0.01) and was shaped by differences in soil moisture, pH, SOM carboxyl content, as well as C and N concentration. Our study highlights the importance of distinguishing between metabolically active microorganisms and the total community, and emphasizes that the same environmental factors shape the total and active communities of bacteria and fungi in this ecosystem. PMID- 27387910 TI - The role of plant-microbiome interactions in weed establishment and control. AB - The soil microbiome plays an important role in the establishment of weeds and invasive plants. They associate with microorganisms supporting their growth and health. Weed management strategies, like tillage and herbicide treatments, to control weeds generally alter soil structure going alongside with changes in the microbial community. Once a weed population establishes in the field, the plants build up a close relationship with the available microorganisms. Seeds or vegetative organs overwinter in soil and select early in the season their own microbiome before crop plants start to vegetate. Weed and crop plants compete for light, nutrition and water, but may differently interact with soil microorganisms. The development of new sequencing technologies for analyzing soil microbiomes has opened up the possibility for in depth analysis of the interaction between 'undesired' plants and crop plants under different management systems. These findings will help us to understand the functions of microorganisms involved in crop productivity and plant health, weed establishment and weed prevention. Exploitation of the knowledge offers the possibility to search for new biocontrol methods against weeds based on soil and plant associated microorganisms. This review discusses the recent advances in understanding the functions of microbial communities for weed/invasive plant establishment and shows new ways to use plant-associated microorganisms to control weeds and invasive plants in different land management systems. PMID- 27387911 TI - Spatial and temporal patterns in the Pelagibacteraceae across an estuarine gradient. AB - Marine bacterial communities show strong spatial and seasonal patterns, often characterized by changes at high taxonomic levels. The Pelagibacteraceae are common members of bacterial communities, with well-documented biogeography at the subclade level. To identify patterns within the subclades, the abundance and diversity of Pelagibacteraceae were analyzed over a two-year period at four stations across an estuarine gradient. Pelagibacteraceae was the most abundant bacterial family, averaging 27% of the community, but varying from 1% to 57% in any one sample. Highest abundances were detected in autumn and winter. Pelagibacteraceae richness was lowest at the most inshore site, and highest in autumn and winter at all sites. Shannon diversity decreased in winter, when a few OTUs dominated the community. Dissolved oxygen, dissolved silicate and prokaryote abundance explained most of the variability in the Pelagibacteraceae communities, with salinity differentiating low salinity communities. The 10 most abundant OTUs included OTUs that varied across sites, with little seasonality as well as those with small site effects, but strong seasonal patterns indicating differences in the niches of individual OTUs. While salinity was important in structuring low salinity communities, higher salinity communities appear to be responding to additional environmental parameters including oxygen, nutrients and other organisms. PMID- 27387912 TI - Hydrocarbon biodegradation by Arctic sea-ice and sub-ice microbial communities during microcosm experiments, Northwest Passage (Nunavut, Canada). AB - The increasing accessibility to navigation and offshore oil exploration brings risks of hydrocarbon releases in Arctic waters. Bioremediation of hydrocarbons is a promising mitigation strategy but challenges remain, particularly due to low microbial metabolic rates in cold, ice-covered seas. Hydrocarbon degradation potential of ice-associated microbes collected from the Northwest Passage was investigated. Microcosm incubations were run for 15 days at -1.7 degrees C with and without oil to determine the effects of hydrocarbon exposure on microbial abundance, diversity and activity, and to estimate component-specific hydrocarbon loss. Diversity was assessed with automated ribosomal intergenic spacer analysis and Ion Torrent 16S rRNA gene sequencing. Bacterial activity was measured by (3)H leucine uptake rates. After incubation, sub-ice and sea-ice communities degraded 94% and 48% of the initial hydrocarbons, respectively. Hydrocarbon exposure changed the composition of sea-ice and sub-ice communities; in sea-ice microcosms, Bacteroidetes (mainly Polaribacter) dominated whereas in sub-ice microcosms, the contribution of Epsilonproteobacteria increased, and that of Alphaproteobacteria and Bacteroidetes decreased. Sequencing data revealed a decline in diversity and increases in Colwellia and Moritella in oil-treated microcosms. Low concentration of dissolved organic matter (DOM) in sub-ice seawater may explain higher hydrocarbon degradation when compared to sea ice, where DOM was abundant and composed of labile exopolysaccharides. PMID- 27387913 TI - Prevalence and correlates of fear of recurrence among adolescent and young adult versus older adult post-treatment cancer survivors. AB - PURPOSE: We sought to (1) assess prevalence of fear of recurrence among cancer survivors diagnosed as adolescent and young adults (AYA; 15-39 years) versus those diagnosed at a later age (40+ years) and (2) identify factors associated with fear of recurrence in each group. METHODS: We used logistic regression to determine the correlates of fear of recurrence by age group at diagnosis among survivors responding to the 2010 LIVESTRONG survey. RESULTS: Prevalence of fear of recurrence was significantly higher among AYA survivors (85.2 %) than those diagnosed at an older age (79.7 %). Among AYA respondents, being employed and less than 5 years off treatment were positively associated with fear of recurrence while those with thyroid cancer and those who participated in a clinical trial were less likely to experience fear of recurrence. Among older adults, receipt of surgery was associated with fear of recurrence whereas having insurance coverage through Medicare or Medicaid and positive patient-provider communication were negatively associated with fear of recurrence. CONCLUSIONS: For both AYA and older adult survivors, changeable factors such as having a more positive cancer care experience may impact fear of recurrence. Our findings highlight the need to identify and understand aspects of the communication process that can be targeted in future interventions with survivors and healthcare providers to ensure that fear of recurrence is being appropriately managed. Factors associated with fear of recurrence differ for AYA and older adult survivors; thus, interventions would likely benefit from tailoring based on age at diagnosis. PMID- 27387914 TI - Updates on feline aelurostrongylosis and research priorities for the next decade. AB - Feline aelurostrongylosis, caused by the metastrongyloid nematode Aelurostrongylus abstrusus, is an important gastropod-borne parasitic lung disease in cats. Infection with A. abstrusus is widespread globally, but the increasing awareness of this parasite and the advent of more sensitive diagnostics have contributed to the apparent increase in its prevalence and geographic expansion. Clinical features may range in severity from subclinical to life-threatening respiratory disease. Parasitological standard techniques, such as visualization of the nematode first larval stage in faecal and respiratory (bronchial mucus or pleural fluid) samples, remain the mainstays of diagnosis. However, diagnosis is evolving with recent advances in serological and molecular testing, which can improve the time to initiation of effective anthelmintic therapy. Despite numerous anthelmintics that are now available as treatment options, the role of host immunity and lifestyle factors in selecting cats that may benefit from more targeted anthelmintic prophylaxis or treatment practice remains unclear and is likely to guide therapeutic choices as newer data become available. This review summarizes the biology, epidemiology, pathophysiology, diagnosis and treatment options currently available for feline aelurostrongylosis. PMID- 27387915 TI - EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus. AB - BACKGROUND: Approximately 50 % of gastric adenocarcinomas belong to a molecular subgroup characterised by chromosomal instability and a strong association with the intestinal histological subtype. This subgroup typically contains alterations in the receptor tyrosine kinase-RAS pathway, for example EGFR or HER2 gene amplifications leading to protein overexpression. In clinical practice, HER2 overexpressing metastatic gastric cancer is known to respond to treatment with anti-HER2 antibodies. By contrast, anti-EGFR antibodies have not been able to provide survival benefit in clinical trials, which, however, have not included patient selection based on the histological subtype or EGFR gene copy number analysis of the tumours. To examine the role of EGFR as a potential biomarker, we studied the prevalence, clinicopathological associations as well as prognostic role of EGFR and HER2 expression and gene amplification in intestinal adenocarcinomas of the stomach, gastro-oesophageal junction and distal oesophagus. METHODS: Tissue samples from 220 patients were analysed with EGFR and HER2 immunohistochemistry. Those samples with moderate/strong staining intensity were further analysed with silver in situ hybridization to quantify gene copy numbers. The results were associated with clinical patient characteristics and survival. RESULTS: Moderate/strong EGFR protein expression was found in 72/220 (32.7 %) and EGFR gene amplification in 31/220 (14.1 %) of the tumours, while moderate/strong HER2 protein expression was detected in 31/220 (14.1 %) and HER2 gene amplification in 29/220 (13.2 %) of the tumours. EGFR and HER2 genes were co amplified in eight tumours (3.6 %). EGFR gene amplification was more common in tumours of distal oesophagus/gastro-oesophageal junction/cardia than in those of gastric corpus (p = 0.013). It was associated with shortened time to cancer recurrence (p = 0.026) and cancer specific survival (p = 0.033). CONCLUSIONS: EGFR gene amplification is relatively common in intestinal adenocarcinomas and associates with decreased survival. It is rarely concurrent with HER2 gene amplification, suggesting that anti-EGFR therapies might be applicable to some patients not eligible for anti-HER2 treatment. Analogous to HER2 testing, determination of EGFR gene amplification status in concert with immunohistochemistry could improve the specificity of patient selection when investigating the possible benefits of anti-EGFR therapies in the treatment of gastric adenocarcinomas. PMID- 27387916 TI - Impact of the UN convention on the rights of persons with disabilities (UN-CRPD) on mental health care research - a systematic review. AB - BACKGROUND: The United Nations Convention on the Rights of Persons with Disabilities (UN-CRPD) aims at stimulating profound changes and social development in many areas of the society. We wanted to examine the impact of the convention on mental health care research up to now by a systematic review. METHODS: We searched relevant electronic databases for empirical studies from the area of mental health which focused directly on the content of the UN-CRPD. RESULTS: One thousand six hundred ten articles were screened, 36 of which fulfilled the inclusion criteria and came from 22 different countries. 25 studies (69 %) are related to persons with intellectual disabilities, only 11 to other mental disorders. Study designs were quantitative and qualitative as well. Issues were realisation of the UN-CRPD, implementation and financing, development of instruments, and attitudes towards the UN-CRPD. CONCLUSIONS: In contrast to possible wide-reaching consequences for the organisation of mental health care, theoretical debates prevail as of yet and empirical research is still scarce. Research on the UN-CRPD is more advanced for intellectual disabilities and provides good suggestions for relevant research aspects in major mental disorders. PMID- 27387917 TI - The Boehringer Ingelheim employee study (Part 2): 10-year cardiovascular diseases risk estimation. AB - BACKGROUND: Cardiovascular disease (CVD) may cause an economic burden to companies, but CVD risk estimations specific to working populations are lacking. AIMS: To estimate the 10-year CVD risk in the Boehringer Ingelheim (BI) employee cohort and analyse the potential effect of hypothetical risk reduction interventions. METHODS: We estimated CVD risk using the Framingham (FRS), PROCAM (PRS) and Reynolds (RRS) risk scores, using cross-sectional baseline data on BI Pharma employees collected from 2005 to 2011. Results were compared using Fisher's exact and Wilcoxon tests. The predictive ability of the score estimates was assessed using receiver-operating characteristics analyses. RESULTS: Among the 4005 study subjects, we estimated 10-year CVD risks of 35% (FRS), 9% (PRS) and 6% (RRS) for men and 10% (FRS), 4% (PRS) and 1% (RRS) for women. One hundred and thirty-four (6%) men and 111 (6%) women employees had current CVD. The best predictors of prevalent CVD were the FRS and the RRS for men [area-under-the curve 0.62 (0.57-0.67) for both]. A hypothetical intervention that would improve systolic blood pressure, HbA1c (for diabetes), C-reactive protein, triglycerides and total and high-density lipoprotein cholesterol by 10% each would potentially reduce expected CVD cases by 36-41% in men and 30-45% in women, and if smoking cessation is incorporated, by 39-45% and 30-55%, respectively, depending on the pre-intervention risk score. CONCLUSIONS: There was a substantial risk of developing CVD in this working cohort. Occupational health programmes with lifestyle interventions for high-risk individuals may be an effective risk reduction measure. PMID- 27387918 TI - Fitness, obesity and risk of asthma among Army trainees. AB - BACKGROUND: Epidemiological data suggest an association between overweight/obesity and asthma. However, less is known about the relationship between physical fitness and asthma. AIMS: To enumerate new-onset asthma diagnoses in Army recruits during the first 2 years of service and determine associations with fitness and excess body fat (EBF) at military entrance. METHODS: New asthma diagnoses over 2 years in Army recruits at six entrance stations were obtained from military health and personnel records. Poisson regression models were used to determine associations of asthma diagnosis with pre-accession fitness testing, EBF and other potential factors. RESULTS: In 9979 weight-qualified and 1117 EBF entrants with no prior history of asthma, 256 new cases of asthma were diagnosed within 2 years of military entry. Low level of fitness, defined by a step test and EBF, was significantly associated with new asthma diagnosis [adjusted incidence rate ratio (IRR), 1.47; 95% confidence interval (CI) 1.11-1.96 and adjusted IRR, 1.53; 95% CI 1.06-2.20, respectively]. CONCLUSIONS: Individuals with low fitness levels, EBF or both are at higher risk of asthma diagnosis in the first 2 years of military service. PMID- 27387919 TI - Bio-inspired metal ions regulate the structure evolution of self-assembled peptide-based nanoparticles. AB - We report an assembly and transformation process of a supramolecular module, BP KLVFF-RGD (BKR) in solution and on specific living cell surfaces for imaging and treatment. The BKR self-assembled into nanoparticles, which further transformed into nanofibers in situ induced by coordination with Ca(2+) ions. PMID- 27387920 TI - The dominance of the private sector in the provision of emergency obstetric care: studies from Gujarat, India. AB - BACKGROUND: India has experienced a steep rise in institutional childbirth. The relative contributions of public and private sector facilities to emergency obstetric care (EmOC) has not been studied in this setting. This paper aims to study in three districts of Gujarat state, India:(a) the availability of EmOC facilities in the public and private sectors; (b) the availability and distribution of human resources for birth attendance in the two sectors; and (c) to benchmark the above against 2005 World Health Report benchmarks (WHR2005). METHODS: A cross-sectional survey of obstetric care facilities reporting 30 or more births in the last three months was conducted (n = 159). Performance of EmOC signal functions and availability of human resources were assessed. RESULTS: EmOC provision was dominated by private facilities (112/159) which were located mainly in district headquarters or small urban towns. The number of basic and comprehensive EmOC facilities was below WHR2005 benchmarks. A high number of private facilities performed C-sections but not all basic signal functions (72/159). Public facilities were the main EmOC providers in rural areas and 40/47 functioned at less than basic EmOC level. The rate of obstetricians per 1000 births was higher in the private sector. CONCLUSIONS: The private sector is the dominant EmOC provider in the state. Given the highly skewed distribution of facilities and resources in the private sector, state led partnerships with the private sector so that all women in the state receive care is important alongside strengthening the public sector. PMID- 27387921 TI - Spatial distribution estimation of malaria in northern China and its scenarios in 2020, 2030, 2040 and 2050. AB - BACKGROUND: Malaria is one of the most severe parasitic diseases in the world. Spatial distribution estimation of malaria and its future scenarios are important issues for malaria control and elimination. Furthermore, sophisticated nonlinear relationships for prediction between malaria incidence and potential variables have not been well constructed in previous research. This study aims to estimate these nonlinear relationships and predict future malaria scenarios in northern China. METHODS: Nonlinear relationships between malaria incidence and predictor variables were constructed using a genetic programming (GP) method, to predict the spatial distributions of malaria under climate change scenarios. For this, the examples of monthly average malaria incidence were used in each county of northern China from 2004 to 2010. Among the five variables at county level, precipitation rate and temperature are used for projections, while elevation, water density index, and gross domestic product are held at their present-day values. RESULTS: Average malaria incidence was 0.107 0/00 per annum in northern China, with incidence characteristics in significant spatial clustering. A GP based model fit the relationships with average relative error (ARE) = 8.127 % for training data (R(2) = 0.825) and 17.102 % for test data (R(2) = 0.532). The fitness of GP results are significantly improved compared with those by generalized additive models (GAM) and linear regressions. With the future precipitation rate and temperature conditions in Special Report on Emission Scenarios (SRES) family B1, A1B and A2 scenarios, spatial distributions and changes in malaria incidences in 2020, 2030, 2040 and 2050 were predicted and mapped. CONCLUSIONS: The GP method increases the precision of predicting the spatial distribution of malaria incidence. With the assumption of varied precipitation rate and temperature, and other variables controlled, the relationships between incidence and the varied variables appear sophisticated nonlinearity and spatially differentiation. Using the future fluctuated precipitation and the increased temperature, median malaria incidence in 2020, 2030, 2040 and 2050 would significantly increase that it might increase 19 to 29 % in 2020, but currently China is in the malaria elimination phase, indicating that the effective strategies and actions had been taken. While the mean incidences will not increase even reduce due to the incidence reduction in high risk regions but the simultaneous expansion of the high-risk areas. PMID- 27387922 TI - Feed-forward neural network model for hunger and satiety related VAS score prediction. AB - BACKGROUND: An artificial neural network approach was chosen to model the outcome of the complex signaling pathways in the gastro-intestinal tract and other peripheral organs that eventually produce the satiety feeling in the brain upon feeding. METHODS: A multilayer feed-forward neural network was trained with sets of experimental data relating concentration-time courses of plasma satiety hormones to Visual Analog Scales (VAS) scores. The network successfully predicted VAS responses from sets of satiety hormone data obtained in experiments using different food compositions. RESULTS: The correlation coefficients for the predicted VAS responses for test sets having i) a full set of three satiety hormones, ii) a set of only two satiety hormones, and iii) a set of only one satiety hormone were 0.96, 0.96, and 0.89, respectively. The predicted VAS responses discriminated the satiety effects of high satiating food types from less satiating food types both in orally fed and ileal infused forms. CONCLUSIONS: From this application of artificial neural networks, one may conclude that neural network models are very suitable to describe situations where behavior is complex and incompletely understood. However, training data sets that fit the experimental conditions need to be available. PMID- 27387923 TI - High levels of immunoglobulin A anti-tissue transglutaminase antibodies at diagnosis are a predictive factor for celiac hepatitis. AB - INTRODUCTION: Celiac hepatitis is characterized by the presence of liver injury in patients with celiac disease that resolves after gluten-free diet. AIM: To evaluate predictive factors of celiac hepatitis at celiac disease diagnosis. METHODS: Retrospective study including 46 adult patients with the diagnosis of celiac disease. RESULTS: Eighty-seven percent were women, with a mean age of 33 +/- 11 years, 87% had a Marsh 3 and 46% (n = 21) had celiac hepatitis. These patients had a median Immunoglobulin A anti-tissue transglutaminase antibody (TTG IgA) level of 208.0 U/ml (p25-p75: 89-1316 U/ml), a mean aspartate aminotransferase of 42 +/- 24 U/L, alanine aminotransferase 50 +/- 28 U/L, alkaline phosphatase 111 +/- 64 U/L, at the time of diagnosis. Median TTG-IgA one year after diagnosis was 9U/ml (p25-p75: 4.5-30.5 U/ml) and 33% of the patients had normal values. At diagnosis, patients without celiac hepatitis had a median TTG-IgA of 77U/ml (p25-p75: 24-288 U/ml), mean aspartate aminotransferase of 23 +/- 4 U/L, alanine aminotransferase 20 +/- 6 U/L, alkaline phosphatase 69 +/- 17 U/L. Median of TTG-IgA one year after diagnosis was 6 U/ml (p25-p75: 3-19 U/ml) and 48% had normal values. The celiac hepatitis group patients had higher values of TTG-IgA (p = 0.007) at diagnosis. There was a statistically significant positive correlation between TTG-IgA and alanine aminotransferase (r = 0.324, p = 0.028) at diagnosis. The odds of having celiac hepatitis was almost 5-fold higher in patients with a TTG-IgA level higher than 310 U/ml (OR = 4.8, 95%CI = 1.213 18.781, p = 0.025). CONCLUSIONS: Higher TTG-IgA levels are a predictive factor for celiac hepatitis in adult patients with celiac disease at diagnosis. PMID- 27387924 TI - The timing of surgical treatment of traumatic facial paralysis: a systematic review. AB - CONCLUSIONS: Surgical decompression performed within 2 weeks yields the best clinical prognosis for patients with TFP. This study also demonstrated that surgical exploration performed within 2 months results in acceptable outcomes. OBJECTIVES: The ideal timing for surgical intervention of traumatic facial paralysis (TFP) is still controversial. A systematic review was performed to appropriately determine the timing of surgical decompression. METHODS: Related studies were identified by searching Pubmed, EMBASE, and Cochrane and reviewing the relevant reference lists until 1 March 2016. Surgical timing was classified into four sub-groups: <2 weeks, 2 weeks-1 month, 1-2 months, and >2 months. RESULTS: Six studies including 119 patients (119 cases) fulfilled the study requirements. The number of patients who achieved perfect recovery of House Brackmanm (H-B) grade 1 was 40 of 119 patients (33.6%). Good results were demonstrated in 94.4% (17/18) of patients managed with surgical decompression within 2 weeks vs 63.4% (64/101) of patients undergoing surgical intervention at >2 weeks (p = 0.009). PMID- 27387926 TI - Cover stories: Making the robotic ray cover. PMID- 27387928 TI - RESEARCH REGULATION. Panel slams plan for human research rules. PMID- 27387925 TI - The Burden of Zoonoses in Kyrgyzstan: A Systematic Review. AB - INTRODUCTION: Zoonotic disease (ZD) pose a serious threat to human health in low income countries. In these countries the human burden of disease is often underestimated due to insufficient monitoring because of insufficient funding. Quantification of the impact of zoonoses helps in prioritizing healthcare needs. Kyrgyzstan is a poor, mountainous country with 48% of the population employed in agriculture and one third of the population living below the poverty line. METHODOLOGY/PRINCIPAL FINDINGS: We have assessed the burden of zoonoses in Kyrgyzstan by conducting a systematic review. We have used the collected data to estimate the burden of ZDs and addressed the underestimation in officially reported disease incidence. The estimated incidences of the ZDs were used to calculate incidence-based Disability Adjusted Life Years (DALYs). This standardized health gap measure enhances comparability between injuries and diseases. The combined burden for alveolar echinococcosis, cystic echinococcosis, brucellosis, campylobacteriosis, congenital toxoplasmosis, non-typhoidal salmonellosis and rabies in Kyrgyzstan in 2013 was 35,209 DALYs [95% Uncertainty interval (UI):13,413-83,777]; 576 deaths [95% UI: 279-1,168] were attributed to these infections. We estimate a combined median incidence of ZDs of 141,583 cases [95% UI: 33,912-250,924] in 2013. The highest burden was caused by non-typhoidal Salmonella and Echinococcus multilocularis, respectively 14,792 DALYs [95% UI: 3,966-41,532] and 11,915 DALYs [95% UI: 4,705-27,114] per year. CONCLUSION/SIGNIFICANCE: The health impact of zoonoses in Kyrgyzstan is substantial, comparable to that of HIV. Community-based surveillance studies and hospital-based registration of all occurrences of zoonoses would increase the accuracy of the estimates. PMID- 27387929 TI - PHYSICS. Long-delayed nuclear center looks set for construction. PMID- 27387931 TI - ECONOMIC GEOLOGY. Massive helium fields found in rift zone of Tanzania. PMID- 27387930 TI - ASTROPHYSICS. Titanic balloon sets record and tantalizes scientists. PMID- 27387932 TI - ROBOTICS. Heartmaker's next step: a ray 'biohybrid'. PMID- 27387933 TI - FUNDING. In Canada, peer-review changes stir outrage. PMID- 27387934 TI - Rewilding Rio. PMID- 27387935 TI - Hurdling obstacles. PMID- 27387936 TI - PALEONTOLOGY. Learning to move on land. PMID- 27387937 TI - CHEMISTRY. Molecular sieves for gas separation. PMID- 27387938 TI - NETWORK ANALYSIS. Network analytics in the age of big data. PMID- 27387939 TI - ENGINEERING. Solar-powering the Internet of Things. PMID- 27387940 TI - Science stands by 2009 fisheries study. PMID- 27387941 TI - Insufficient research on land grabbing. PMID- 27387942 TI - Mexico struggles to keep foreign grants. PMID- 27387943 TI - Comment on "Long-term climate forcing by atmospheric oxygen concentrations". AB - Poulsen et al (Reports, 12 June 2015, p. 1238) argued that lower atmospheric oxygen levels during the Phanerozoic would have given a warmer climate. However, radiative and atmospheric structure changes under lower pressure both cause cooling, making their result unusual in that a hierarchy of models gives opposing results. Scrutiny of how radiative and cloud processes were represented, and a mechanistic explanation of the results, are required. PMID- 27387944 TI - Response to Comment on "Long-term climate forcing by atmospheric oxygen concentrations". AB - Goldblatt argues that a decrease in pressure broadening of absorption lines in an atmosphere with low oxygen leads to an increase in outgoing longwave radiation and atmospheric cooling. We demonstrate that cloud and water vapor feedbacks in a global climate model compensate for these decreases and lead to atmospheric warming. PMID- 27387945 TI - A metal-organic framework-based splitter for separating propylene from propane. AB - The chemical industry is dependent on the olefin/paraffin separation, which is mainly accomplished by using energy-intensive processes. We report the use of reticular chemistry for the fabrication of a chemically stable fluorinated metal organic framework (MOF) material (NbOFFIVE-1-Ni, also referred to as KAUST-7). The bridging of Ni(II)-pyrazine square-grid layers with (NbOF5)(2-) pillars afforded the construction of a three-dimensional MOF, enclosing a periodic array of fluoride anions in contracted square-shaped channels. The judiciously selected bulkier (NbOF5)(2-) caused the looked-for hindrance of the previously free rotating pyrazine moieties, delimiting the pore system and dictating the pore aperture size and its maximum opening. The restricted MOF window resulted in the selective molecular exclusion of propane from propylene at atmospheric pressure, as evidenced through multiple cyclic mixed-gas adsorption and calorimetric studies. PMID- 27387946 TI - Thermally stable single-atom platinum-on-ceria catalysts via atom trapping. AB - Catalysts based on single atoms of scarce precious metals can lead to more efficient use through enhanced reactivity and selectivity. However, single atoms on catalyst supports can be mobile and aggregate into nanoparticles when heated at elevated temperatures. High temperatures are detrimental to catalyst performance unless these mobile atoms can be trapped. We used ceria powders having similar surface areas but different exposed surface facets. When mixed with a platinum/aluminum oxide catalyst and aged in air at 800 degrees C, the platinum transferred to the ceria and was trapped. Polyhedral ceria and nanorods were more effective than ceria cubes at anchoring the platinum. Performing synthesis at high temperatures ensures that only the most stable binding sites are occupied, yielding a sinter-resistant, atomically dispersed catalyst. PMID- 27387947 TI - Tail use improves performance on soft substrates in models of early vertebrate land locomotors. AB - In the evolutionary transition from an aquatic to a terrestrial environment, early tetrapods faced the challenges of terrestrial locomotion on flowable substrates, such as sand and mud of variable stiffness and incline. The morphology and range of motion of appendages can be revealed in fossils; however, biological and robophysical studies of modern taxa have shown that movement on such substrates can be sensitive to small changes in appendage use. Using a biological model (the mudskipper), a physical robot model, granular drag measurements, and theoretical tools from geometric mechanics, we demonstrate how tail use can improve robustness to variable limb use and substrate conditions. We hypothesize that properly coordinated tail movements could have provided a substantial benefit for the earliest vertebrates to move on land. PMID- 27387949 TI - Higher-order organization of complex networks. AB - Networks are a fundamental tool for understanding and modeling complex systems in physics, biology, neuroscience, engineering, and social science. Many networks are known to exhibit rich, lower-order connectivity patterns that can be captured at the level of individual nodes and edges. However, higher-order organization of complex networks--at the level of small network subgraphs--remains largely unknown. Here, we develop a generalized framework for clustering networks on the basis of higher-order connectivity patterns. This framework provides mathematical guarantees on the optimality of obtained clusters and scales to networks with billions of edges. The framework reveals higher-order organization in a number of networks, including information propagation units in neuronal networks and hub structure in transportation networks. Results show that networks exhibit rich higher-order organizational structures that are exposed by clustering based on higher-order connectivity patterns. PMID- 27387948 TI - Phototactic guidance of a tissue-engineered soft-robotic ray. AB - Inspired by the relatively simple morphological blueprint provided by batoid fish such as stingrays and skates, we created a biohybrid system that enables an artificial animal--a tissue-engineered ray--to swim and phototactically follow a light cue. By patterning dissociated rat cardiomyocytes on an elastomeric body enclosing a microfabricated gold skeleton, we replicated fish morphology at 1/10 scale and captured basic fin deflection patterns of batoid fish. Optogenetics allows for phototactic guidance, steering, and turning maneuvers. Optical stimulation induced sequential muscle activation via serpentine-patterned muscle circuits, leading to coordinated undulatory swimming. The speed and direction of the ray was controlled by modulating light frequency and by independently eliciting right and left fins, allowing the biohybrid machine to maneuver through an obstacle course. PMID- 27387950 TI - S-Acylation of the cellulose synthase complex is essential for its plasma membrane localization. AB - Plant cellulose microfibrils are synthesized by a process that propels the cellulose synthase complex (CSC) through the plane of the plasma membrane. How interactions between membranes and the CSC are regulated is currently unknown. Here, we demonstrate that all catalytic subunits of the CSC, known as cellulose synthase A (CESA) proteins, are S-acylated. Analysis of Arabidopsis CESA7 reveals four cysteines in variable region 2 (VR2) and two cysteines at the carboxy terminus (CT) as S-acylation sites. Mutating both the VR2 and CT cysteines permits CSC assembly and trafficking to the Golgi but prevents localization to the plasma membrane. Estimates suggest that a single CSC contains more than 100 S acyl groups, which greatly increase the hydrophobic nature of the CSC and likely influence its immediate membrane environment. PMID- 27387951 TI - Climate-driven regime shift of a temperate marine ecosystem. AB - Ecosystem reconfigurations arising from climate-driven changes in species distributions are expected to have profound ecological, social, and economic implications. Here we reveal a rapid climate-driven regime shift of Australian temperate reef communities, which lost their defining kelp forests and became dominated by persistent seaweed turfs. After decades of ocean warming, extreme marine heat waves forced a 100-kilometer range contraction of extensive kelp forests and saw temperate species replaced by seaweeds, invertebrates, corals, and fishes characteristic of subtropical and tropical waters. This community-wide tropicalization fundamentally altered key ecological processes, suppressing the recovery of kelp forests. PMID- 27387952 TI - Cilia-based flow network in the brain ventricles. AB - Cerebrospinal fluid conveys many physiologically important signaling factors through the ventricular cavities of the brain. We investigated the transport of cerebrospinal fluid in the third ventricle of the mouse brain and discovered a highly organized pattern of cilia modules, which collectively give rise to a network of fluid flows that allows for precise transport within this ventricle. We also discovered a cilia-based switch that reliably and periodically alters the flow pattern so as to create a dynamic subdivision that may control substance distribution in the third ventricle. Complex flow patterns were also present in the third ventricles of rats and pigs. Our work suggests that ciliated epithelia can generate and maintain complex, spatiotemporally regulated flow networks. PMID- 27387953 TI - The questions that opened doors. PMID- 27387954 TI - An intervention targeting fundamental values among caregivers at residential facilities: effects of a cluster-randomized controlled trial on residents' self reported empowerment, person-centered climate and life satisfaction. AB - BACKGROUND: In Sweden the national fundamental values for care of older people state that care should ensure that they can live in dignity and with a sense of well-being. Our hypothesis was that a caregiver intervention targeting the national fundamental values would improve perceived empowerment, person-centered climate and life satisfaction among older people living in residential facilities. METHODS: The study was a cluster-randomized controlled trial with a pre- and one post-test design, conducted in 27 units (17 study units) at 12 residential facilities for older people in five municipalities in central Sweden. The units in each municipality were randomly assigned to intervention or control group. The caregiver intervention was carried out using an interpretative approach with eight guided face-to-face seminars, where self-reflection and dialogue were used. Data were collected using questionnaires. The number of residents was 43 (78 %) in the intervention group and 37 (71 %) in the control group. The Chi-square test and Mann-Whitney U-tests were performed to detect differences between groups and Wilcoxon signed rank tests to explore differences in change over time within groups. Furthermore, generalized estimating equation (GEE) models were used to study effects of the intervention controlling for clustering effects. RESULTS: Primary outcome measures were empowerment, person centered climate and life satisfaction. In the intervention group, improvements at follow-up were found in residents' self-reported empowerment (n = 42; p = 0.001, Median difference 4.0, 95 % CI 1.5;6.0), person-centered climate (n = 42; p <=0.001, Median difference 8.0, 95 % CI 4.5;11.4) and life satisfaction regarding the factor quality of everyday activities (n = 40; p = 0.033, Median difference 9.7, 95 % CI 1.0;21.9) while disempowerment decreased (n = 43; p = 0.018, Median difference -1.3, 95 % CI -2.0;0.0). In the control group person centered climate decreased (n = 37; p = 0.002, Median difference -8.5, 95 % CI 13.6;-3.0) and quality of everyday activities (n = 36; p = 0.012, Median difference -11.6, 95 % CI-21.7;-3.4). Change over time between groups was significant for empowerment (p = 0.001, Median difference 6.0, 95 % CI 3.0;9.0), disempowerment (p = 0.006, Median difference -2.0, 95 % CI -4.0;-1.0) and person centered climate (p <= 0.001, Median difference 16.0, 95 % CI 9.7;23.0) and for life satisfaction regarding the factor quality of everyday activities (p = 0.002, Median difference 22.1, 95 % CI 8.2;37.4). Results of GEE confirmed earlier results; revealed interaction effects for empowerment (parameter estimate -5.0, 95 % CI -8.3;-1.8), person-centered climate (parameter estimate -16.7, 95 % CI 22.4;-10.9) and life satisfaction regarding the factor quality of everyday activities (parameter estimate -25.9, 95 % CI -40.3;-11.5). CONCLUSION: When the Swedish national fundamental values were put into practice increases in empowerment, person-centered climate and quality of everyday activities were found among older people with intact cognitive ability living in residential facilities. Limitations to consider are the differences between the two groups at baseline, drop-outs and that neither the data collector nor the outcome assessors were blinded to group assignment of participants. TRIAL REGISTRATION: The study was registered in ISRCTN92658034 in January 2013. PMID- 27387955 TI - Fluorescent imaging of superficial head and neck squamous cell carcinoma using a gamma-glutamyltranspeptidase-activated targeting agent: a pilot study. AB - BACKGROUND: Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. gamma-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. METHODS: gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. RESULTS: All four gGlu-HMRG applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. CONCLUSIONS: Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC. PMID- 27387956 TI - Genome-wide search identifies a gene-gene interaction between 20p13 and 2q14 in asthma. AB - BACKGROUND: Many studies have attempted to identify gene-gene interactions affecting asthma susceptibility. However, these studies have typically used candidate gene approaches in limiting the genetic search space, and there have been few searches for gene-gene interactions on a genome-wide scale. We aimed to conduct a genome-wide gene-gene interaction study for asthma, using data from the GABRIEL Consortium. RESULTS: A two-stage study design was used, including a screening analysis (N = 1625 subjects) and a follow-up analysis (N = 5264 subjects). In the screening analysis, all pairwise interactions among 301,547 SNPs were evaluated, encompassing a total of 4.55 * 10(10) interactions. Those with a screening interaction p-value < 10(-5) were evaluated in the follow-up analysis. No interaction selected from the screening analysis met strict statistical significance in the follow-up (p-value < 1.45 * 10(-7)). However, the top-ranked interaction (rs910652 [20p13] * rs11684871 [2q14]) in the follow-up (p value = 1.58 * 10(-6)) was significant in one component of a replication analysis. This interaction was notable in that rs910652 is located within 78 kilobases of ADAM33, which is one of the most well studied asthma susceptibility genes. In addition, rs11684871 is located in or near GLI2, which may have biologically relevant roles in asthma. CONCLUSIONS: Using a genome-wide approach, we identified and found suggestive evidence of replication for a gene-gene interaction in asthma involving loci that are potentially highly relevant in asthma pathogenesis. PMID- 27387957 TI - Food Waste Fermentation to Fumaric Acid by Rhizopus arrhizus RH7-13. AB - Fumaric acid as a four-carbon unsaturated dicarboxylic acid is widely used in the food and chemical industries. Food waste (FW), rich in carbohydrates and protein, is a promising potential feedstock for renewable bio-based chemicals. In this research, we investigated the capability of Rhizopus arrhizus RH7-13 in producing fumaric acid from FW. The liquid fraction of the FW (L-FW) was proven to be the best seed culture medium in our research. When it was however used to be fermentation medium, the yield of fumaric acid reached 32.68 g/L, at a volumetric production of 0.34 g/L h. The solid fraction of FW mixed with water (S-FW) could also be used as fermentation medium when a certain amount of glucose was added, and the yield of fumaric acid reached 31.26 g/L. The results indicated that both fractions of FW could be well utilized in fermentation process and it could replace a part of common carbon, nitrogen, and nutrient. The process has an application potential since reducing the costs of raw materials. PMID- 27387958 TI - The Development of Leucine Dehydrogenase and Formate Dehydrogenase Bifunctional Enzyme Cascade Improves the Biosynthsis of L-tert-Leucine. AB - Leucine dehydrogenase (LDH) and formate dehydrogenase (FDH) were assembled together based on a high-affinity interaction between two different cohesins in a miniscaffoldin and corresponding dockerins in LDH and FDH. The miniscaffoldin with two enzymes was further absorbed by regenerated amorphous cellulose (RAC) to form a bifunctional enzyme complex (miniscaffoldin with LDH and FDH adsorbed by RAC, RSLF) in vitro. The enzymatic characteristics of the bifunctional enzyme complex and free enzymes mixture were systematically compared. The synthesis of L tert-leucine by the RSLF and free enzyme mixture were compared under different concentrations of enzymes, coenzyme, and substrates. The initial L-tert-leucine production rate by RSLF was enhanced by 2-fold compared with that of the free enzyme mixture. Ninety-one grams per liter of L-tert-leucine with an enantiomeric purity of 99 % e.e. was obtained by RSLF multienzyme catalysis. The results indicated that the bifuntional enzyme complex based on cohesin-dockerin interaction has great potential in the synthesis of L-tert-leucine. PMID- 27387959 TI - Synchrotron-based Nickel Mossbauer Spectroscopy. AB - We used a novel experimental setup to conduct the first synchrotron-based (61)Ni Mossbauer spectroscopy measurements in the energy domain on Ni coordination complexes and metalloproteins. A representative set of samples was chosen to demonstrate the potential of this approach. (61)NiCr2O4 was examined as a case with strong Zeeman splittings. Simulations of the spectra yielded an internal magnetic field of 44.6 T, consistent with previous work by the traditional (61)Ni Mossbauer approach with a radioactive source. A linear Ni amido complex, (61)Ni{N(SiMe3)Dipp}2, where Dipp = C6H3-2,6-(i)Pr2, was chosen as a sample with an "extreme" geometry and large quadrupole splitting. Finally, to demonstrate the feasibility of metalloprotein studies using synchrotron-based (61)Ni Mossbauer spectroscopy, we examined the spectra of (61)Ni-substituted rubredoxin in reduced and oxidized forms, along with [Et4N]2[(61)Ni(SPh)4] as a model compound. For each of the above samples, a reasonable spectrum could be obtained in ~1 d. Given that there is still room for considerable improvement in experimental sensitivity, synchrotron-based (61)Ni Mossbauer spectroscopy appears to be a promising alternative to measurements with radioactive sources. PMID- 27387961 TI - Management of renal cell carcinoma in young patients and patients with hereditary syndromes. AB - PURPOSE OF REVIEW: Individuals that present with renal cell carcinoma at an early age deserve special attention because they are more likely to harbor an inherited predisposition and may require unique treatment strategies. RECENT FINDINGS: In recent years, there has been a significant increase in the number of characterized hereditary syndromes, many of which may predispose to kidney cancer. Although hereditary kidney cancer accounts for only 5-8% of kidney cancers, it should be considered in anyone with an early age of onset. These uncommon presentations should prompt consideration for genetic evaluation for germline alterations or somatic alterations associated with translocations. Treatment of kidney cancer in young individuals must also consider the late risks of nephron loss, the uncertainty with long-term follow-up after ablation, and the need for years of surveillance not only for the treated tumor but for de novo lesions in a patient with a greater risk of multifocality. SUMMARY: Early age of onset should raise concern for a hereditary renal cell carcinoma syndrome and should prompt consideration for genetic counseling to review personal and family history and determine if testing is indicated. Despite advancements in this field, significant work remains to fully delineate the management strategies for young individuals with and without hereditary cancer syndromes. PMID- 27387960 TI - Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells. AB - The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 MUmol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients. PMID- 27387962 TI - Metastatic surgery in testis cancer. AB - PURPOSE OF REVIEW: In testis cancer, prognosis is excellent even in metastatic disease. Treatment and timing of patients with multiple metastatic deposits can be challenging. This review was performed to underline the current guideline recommendations. RECENT FINDINGS: Depending on the primary histology, the indication of further surgical resections differ. In seminoma, residual tumor resections are performed according to the results of a flouoro-deoxy-D-glucose PET. Positive results must be considered critically, and to recent results it is advisable to first repeat flouoro-deoxy-D-glucose-PET to avoid overtreatment. In nonseminomatous germ cell cancer, complete remissions in good prognosis patients are followed and can be spared from surgery. All other patients still need to undergo postchemotherapy retroperitoneal lymph node dissection. In bone metastases, significant histology is found in 80% so that one should go for complete resection. In liver metastases, resections can be performed according to the histology in the retroperitoneum. Both resections, including vessel replacement, are usually performed in one session underlining the complex multidisciplinary approach. Pulmonal metastases, at least in one lobe, need to be resected. Brain metastases are rare with no standard treatment recommendation. SUMMARY: Every patient should be presented in a multidisciplinary tumor board. Surgical interventions should be done in tertiary referral centers to achieve the best oncologic outcome and reduced morbidity. PMID- 27387963 TI - Cation exchange synthesis of uniform PbSe/PbS core/shell tetra-pods and their use as near-infrared photodetectors. AB - In this work we explore the preparation of complex-shaped semiconductor nanostructures composed of different materials via a cationic exchange process in which the cations of the original semiconductor nanostructure are replaced by cations of different metals with preservation of the shape and the anionic framework of the nanocrystals. Utilizing this cation exchange method, we synthesized two new tetrapods for the first time: Cu2-xSe/Cu2-xS and PbSe/PbS, both prepared from CdSe/CdS tetrapods as 'templates'. We also fabricated near infrared (NIR) photodetectors with a very simple architecture comprising a PbSe/PbS tetrapod layer between two Au electrodes on a glass substrate. When illuminated by a NIR laser, these devices are capable of achieving a responsivity of 11.9 A W(-1) without the use of ligand-exchange processes, thermal annealing or hybrid device architecture. Transient absorption spectroscopy was carried out on these PbSe/PbS tetrapods, the results of which suggest that the branched morphology contributes in part to device performance. Investigation of the charge dynamics of the PbSe/PbS tetrapods revealed an extremely long-lived exciton recombination lifetime of ~17 ms, which can result in enhanced photoconductive gain. Overall, these heterostructured tetrapods showcase simultaneously the importance of nanoparticle shape, band structure, and surface chemistry in the attainment of NIR photodetection. PMID- 27387964 TI - Prospective Study of Repeated Biopsy Feasibility and Acquired Resistance at Disease Progression in Patients With Advanced EGFR Mutant Lung Cancer Treated With Erlotinib in a Phase 2 Trial. PMID- 27387965 TI - Randomized trials are frequently fragmented in multiple secondary publications. AB - OBJECTIVE: To assess the frequency and features of secondary publications of randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: For 191 RCTs published in high-impact journals in 2009, we searched for secondary publications coauthored by at least one same author of the primary trial publication. We evaluated the probability of having secondary publications, characteristics of the primary trial publication that predict having secondary publications, types of secondary analyses conducted, and statistical significance of those analyses. RESULTS: Of 191 primary trials, 88 (46%) had a total of 475 secondary publications by 2/2014. Eight trials had >10 (up to 51) secondary publications each. In multivariable modeling, the risk of having subsequent secondary publications increased 1.32-fold (95% CI 1.05-1.68) per 10-fold increase in sample size, and 1.71-fold (95% CI 1.19-2.45) in the presence of a design article. In a sample of 197 secondary publications examined in depth, 193 tested different hypotheses than the primary publication. Of the 193, 43 tested differences between subgroups, 85 assessed predictive factors associated with an outcome of interest, 118 evaluated different outcomes than the original article, 71 had differences in eligibility criteria, and 21 assessed different durations of follow-up; 176 (91%) presented at least one analysis with statistically significant results. CONCLUSIONS: Approximately half of randomized trials in high impact journals have secondary publications published with a few trials followed by numerous secondary publications. Almost all of these publications report some statistically significant results. PMID- 27387966 TI - Evidence & Gap Maps: A tool for promoting evidence informed policy and strategic research agendas. AB - A range of organizations are engaged in the production of evidence on the effects of health, social, and economic development programs on human welfare outcomes. However, evidence is often scattered around different databases, web sites, and the gray literature and is often presented in inaccessible formats. Lack of overview of the evidence in a specific field can be a barrier to the use of existing research and prevent efficient use of limited resources for new research. Evidence & Gap Maps (EGMs) aim to address these issues and complement existing synthesis and mapping approaches. EGMs are a new addition to the tools available to support evidence-informed policymaking. To provide an accessible resource for researchers, commissioners, and decision makers, EGMs provide thematic collections of evidence structured around a framework which schematically represents the types of interventions and outcomes of relevance to a particular sector. By mapping the existing evidence using this framework, EGMs provide a visual overview of what we know and do not know about the effects of different programs. They make existing evidence available, and by providing links to user-friendly summaries of relevant studies, EGMs can facilitate the use of existing evidence for decision making. They identify key "gaps" where little or no evidence from impact evaluations and systematic reviews is available and can be a valuable resource to inform a strategic approach to building the evidence base in a particular sector. The article will introduce readers to the concept and methods of EGMs and present a demonstration of the EGM tool using existing examples. PMID- 27387968 TI - In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme Q10 and N-acetylcysteine. AB - The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicity in vivo and in in vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation. All of these effects were significantly (p < 0.05) inhibited by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Similar outcomes were obtained from the in vivo experiments. Liver function enzyme test and histopathological evaluation confirmed RIS-(6 mg/kg) induced damage. Based on these results, it is suggested that RIS-induced liver toxicity is associated with mitochondrial/lysosomal cross talk following the initiation of oxidative stress. Thus, the use of CoQ10 and/or NAC seems to be a safe therapeutic option in this context. PMID- 27387967 TI - Hypothalamic kappa opioid receptor mediates both diet-induced and melanin concentrating hormone-induced liver damage through inflammation and endoplasmic reticulum stress. AB - The opioid system is widely known to modulate the brain reward system and thus affect the behavior of humans and other animals, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (kappaOR) and adenoviral vectors overexpressing or silencing kappaOR were stereotaxically delivered in the lateral hypothalamic area (LHA) of rats. Vagal denervation was performed to assess its effect on liver metabolism. Endoplasmic reticulum (ER) stress was inhibited by pharmacological (tauroursodeoxycholic acid) and genetic (overexpression of the chaperone glucose-regulated protein 78 kDa) approaches. The peripheral effects on lipid metabolism were assessed by histological techniques and western blot. We show that in the LHA kappaOR directly controls hepatic lipid metabolism through the parasympathetic nervous system, independent of changes in food intake and body weight. kappaOR colocalizes with melanin concentrating hormone receptor 1 (MCH-R1) in the LHA, and genetic disruption of kappaOR reduced melanin concentrating hormone-induced liver steatosis. The functional relevance of these findings was given by the fact that silencing of kappaOR in the LHA attenuated both methionine choline deficient, diet-induced and choline-deficient, high-fat diet-induced ER stress, inflammation, steatohepatitis, and fibrosis, whereas overexpression of kappaOR in this area promoted liver steatosis. Overexpression of glucose-regulated protein 78 kDa in the liver abolished hypothalamic kappaOR-induced steatosis by reducing hepatic ER stress. CONCLUSIONS: This study reveals a novel hypothalamic parasympathetic circuit modulating hepatic function through inflammation and ER stress independent of changes in food intake or body weight; these findings might have implications for the clinical use of opioid receptor antagonists. (Hepatology 2016;64:1086-1104). PMID- 27387969 TI - Marked Differences in Mucosal Immune Responses Induced in Ileal versus Jejunal Peyer's Patches to Mycobacterium avium subsp. paratuberculosis Secreted Proteins following Targeted Enteric Infection in Young Calves. AB - In cattle, Mycobacterium avium subsp. paratuberculosis infection is primarily mediated through M cells overlying Peyer's patches (PP) in the ileum. The capacity of M. avium subsp. paratuberculosis to invade ileal PP (IPP) versus discrete PP in the jejunum (JPP) and subsequent differences in mucosal immune responses were investigated. Intestinal segments were surgically prepared in both mid-jejunum, containing two JPPs, and in terminal small intestine containing continuous IPP. M. avium subsp. paratuberculosis (109 CFU) was injected into the lumen of half of each intestinal segment when calves were 10-14 days-old and infection confirmed 1-2 months later by PCR and immunohistochemistry. Thirteen recombinant M. avium subsp. paratuberculosis proteins, previously identified as immunogenic, were used to analyze pathogen-specific B- and T-cell responses in PP and mesenteric lymph nodes. IgA plasma cell responses to 9 of 13 recombinant proteins were detected in JPP but not in IPP. Secretory IgA reacting in ELISA with 9 of the 13 recombinant proteins was detected in luminal contents from both jejunal and ileal segments. These observations support the conclusion that pathogen-specific IgA B cells were induced in JPP but not IPP early after a primary infection. The presence of secretory IgA in intestinal contents is consistent with dissemination of IgA plasma cells from the identified mucosa associated immune induction sites. This is the first direct evidence for M. avium subsp. paratuberculosis uptake by bovine JPP and for local induction of pathogen specific IgA plasma cell responses after enteric infection. We also provide evidence that bacterial invasion of IPP, a primary B lymphoid tissue, provides a novel strategy to evade induction of mucosal immune responses. Over 60% of PPs in the newborn calf small intestine is primary lymphoid tissue, which has significant implications when designing oral vaccines or diagnostic tests to detect early M. avium subsp. paratuberculosis infections. PMID- 27387970 TI - Single-Use Detergent Sacs: A Retrospective Multicenter Canadian Review of Emergency Department Cases. AB - BACKGROUND: Single-use detergent sacs (SUDS) are widely used in North America and Europe with emerging literature on their toxicity. This is the first Canadian multicenter study aimed to quantify and compare SUDS exposures to traditional detergent exposures. METHODS: A retrospective review of the Canadian Hospitals Injury Reporting and Prevention Program databases was conducted at the Hospital for Sick Children in Toronto, Alberta Children's Hospital in Calgary and the Stollery Children's Hospital in Edmonton. All exposures presenting to these 3 centers between 2009 and 2014 were identified, a case form was completed, and data were analyzed. RESULTS: Forty cases of SUDS exposure were identified alongside 35 cases of traditional detergent exposure during the study period resulting in an incidence of 3.16 SUDS exposures per million children per year presenting to tertiary pediatric emergency departments (EDs). In contrast, traditional detergent exposures had an incidence of 2.78 exposures per million children per year presenting to tertiary pediatric EDs over the study period. Although there was no change in incidence of exposure to traditional detergent over the study period, there was an increase in the incidence of SUDS exposures from 2010 to 2013, with a decrease seen in 2014. There was no significant difference seen in age, sex, location of exposure, transportation to hospital, morbidity, or mortality associated with SUDS exposures compared with traditional detergent exposure. Although not statistically more likely to cause long-term complications, SUDS-exposed children required more follow-up visits to health care providers than traditional detergents. CONCLUSIONS: This multicenter study is the first to establish the incidence of SUDS and traditional detergent exposure in 3 Canadian cities. Overall, the frequency of exposure to detergents both traditional and SUDS-is very low. Given the increase in SUDS exposure seen from 2011 to 2013, alongside larger sales of SUDS, continued efforts are required to monitor exposures, and reduce potential exposures to SUDS and traditional detergents in the future. PMID- 27387971 TI - Randomized Trial of Intranasal Fentanyl Versus Intravenous Morphine for Abscess Incision and Drainage. AB - OBJECTIVES: Abscess incision and drainage (I&D) are painful and distressing procedures in children. Intranasal (IN) fentanyl is an effective analgesic for reducing symptomatic pain associated with fractures and burns but has not been studied for reducing procedural pain during abscess I&D. Our objective was to compare the analgesic efficacy of IN fentanyl with intravenous (IV) morphine for abscess I&D in children. METHODS: We performed a randomized noninferiority trial in children aged 4 to 18 years undergoing abscess I&D in a pediatric emergency department. Patients received IN fentanyl (2 MUg/kg; maximum, 100 MUg) or IV morphine (0.1 mg/kg; maximum, 8 mg). The primary outcome, determined independently by blinded assessors, was the Observational Scale of Behavioral Distress-Revised (OSBD-R). The prestated margin of noninferiority (Delta) was 1.80. Secondary outcomes included self-reported pain, treatment failure, and patient and parental satisfaction. RESULTS: We enrolled 20 children (median age, 15.4 years), 10 in each group. The difference between total OSBD-R scores was 13.45 (95% confidence interval, -24.24 to -2.67), favoring IN fentanyl.There was less self-reported pain in patients who received IN fentanyl immediately after the procedure. Four patients (40%) receiving IV morphine had treatment failures and required moderate sedation or had the procedure terminated. More patients who received IN fentanyl were satisfied with the analgesic administered compared with those who received IV morphine. CONCLUSIONS: In a small sample of children aged 4 to 18 years undergoing abscess I&D, IN fentanyl was noninferior, and potentially superior, to IV morphine for reducing procedural pain and distress. PMID- 27387972 TI - Timely Hemodynamic Resuscitation and Outcomes in Severe Pediatric Traumatic Brain Injury: Preliminary Findings. AB - OBJECTIVES: Early resuscitation may improve outcomes in pediatric traumatic brain injury (TBI). We examined the association between timely treatment of hypotension and hypoxia during early care (prehospital or emergency department locations) and discharge outcomes in children with severe TBI. METHODS: Hypotension was defined as systolic blood pressure less than 70 + 2 (age in years), and hypoxia was defined as PaO2 less than 60 mm Hg or oxygen saturation less than 90% in accordance with the 2003 Brain Trauma Foundation guidelines. Timely treatment of hypotension and hypoxia during early care was defined as the treatment within 30 minutes of a documented respective episode. Two hundred thirty-six medical records of children younger than 18 years with severe TBI from 5 regional pediatric trauma centers were examined. Main outcomes were in-hospital mortality and discharge Glasgow Outcome Scale (GOS) score. RESULTS: Hypotension occurred in 26% (60/234) during early care and was associated with in-hospital mortality (23.3% vs 8.6%; P = 0.01). Timely treatment of hypotension during early care occurred in 92% (55/60) by use of intravenous fluids, blood products, or vasopressors and was associated with reduced in-hospital mortality [adjusted relative risk (aRR), 0.46; 95% confidence interval, 0.24-0.90] and less likelihood of poor discharge GOS (aRR, 0.54; 95% confidence interval, 0.39-0.76) when compared to children with hypotension who were not treated in a timely manner. Early hypoxia occurred in 17% (41/236) and all patients received timely oxygen treatment. CONCLUSIONS: Timely resuscitation during early care was common and associated with lower in-hospital mortality and favorable discharge GOS in severe pediatric TBI. PMID- 27387973 TI - Two Inducible Prophages of an Antarctic Pseudomonas sp. ANT_H14 Use the Same Capsid for Packaging Their Genomes - Characterization of a Novel Phage Helper Satellite System. AB - Two novel prophages FAH14a and FAH14b of a psychrotolerant Antarctic bacterium Pseudomonas sp. ANT_H14 have been characterized. They were simultaneously induced with mitomycin C and packed into capsids of the same size and protein composition. The genome sequences of FAH14a and FAH14b have been determined. FAH14b, the phage with a smaller genome (16,812 bp) seems to parasitize FAH14a (55,060 bp) and utilizes its capsids, as only the latter encodes a complete set of structural proteins. Both viruses probably constitute a phage helper-satellite system, analogous to the P2-P4 duo. This study describes the architecture and function of the FAH14a and FAH14b genomes. Moreover, a functional analysis of a FAH14a-encoded lytic enzyme and a DNA methyltransferase was performed. In silico analysis revealed the presence of the homologs of FAH14a and FAH14b in other Pseudomonas genomes, which may suggest that helper-satellite systems related to the one described in this work are common in pseudomonads. PMID- 27387975 TI - Trehalose-based Janus cyclooligosaccharides: the "Click" synthesis and DNA directed assembly into pH-sensitive transfectious nanoparticles. AB - The convergent preparation of Janus molecular nanoparticles by thiourea "clicking" of alpha,alpha'-trehalose halves has been implemented; the strategy allows access to macrocyclic derivatives with seggregated cationic and lipophilic domains that in the presence of DNA undergo pH-dependent self-assembly into lamellar superstructures, as established by electrochemical, structural (SAXS), microscopical (TEM) and computational techniques, that mediate transfection in vitro and in vivo. PMID- 27387974 TI - EDTA soluble chemical components and the conditioned medium from mobilized dental pulp stem cells contain an inductive microenvironment, promoting cell proliferation, migration, and odontoblastic differentiation. AB - BACKGROUND: The critical challenge in tissue engineering is to establish an optimal combination of stem cells, signaling morphogenetic molecules, and extracellular matrix scaffold/microenvironment. The extracellular matrix components of teeth may be reconstituted as an inductive microenvironment in an ectopic tooth transplantation bioassay. Thus, the isolation and identification of the chemical components of the inductive microenvironment in pulp/dentin regeneration will accelerate progress towards the goal of tissue engineering of the tooth. METHODS: The teeth demineralized in 0.6 M hydrochloric acid were sequentially extracted by 4.0 M guanidine hydrochloride (GdnHCl), pH 7.4, and 0.5 M ethylenediaminetetraacetic acid (EDTA), pH 7.4. The extracted teeth were transplanted into an ectopic site in severe combined immunodeficiency (SCID) mice with mobilized dental pulp stem cells (MDPSCs). The unextracted tooth served as a positive control. Furthermore, the soluble components for the inductive microenvironment, the GdnHCl extracts, or the EDTA extracts together with or without MDPSC conditioned medium (CM) were reconstituted systematically with autoclaved teeth in which the chemical components were completely inactivated and only the physical microenvironment was preserved. Their pulp/dentin regenerative potential and angiogenic potential were compared 28 days after ectopic tooth transplantation by histomorphometry and real-time RT-PCR analysis. RESULTS: Expression of an odontoblastic marker, enamelysin, and a pulp marker, thyrotropin releasing hormone degrading enzyme (TRH-DE), was lower, and expression of a periodontal cell marker, anti-asporin/periodontal ligament-associated protein 1 (PLAP-1), was higher in the transplant of the EDTA-extracted teeth compared with the GdnHCl-extracted teeth. The autoclaved teeth reconstituted with the GdnHCl extracts or the EDTA extracts have weak regenerative potential and minimal angiogenic potential, and the CM significantly increased this potential. Combinatorial effects of the EDTA extracts and the CM on pulp/dentin regeneration were demonstrated in vivo, consistent with their in-vitro effects on enhanced proliferation, migration, and odontoblastic differentiation. CONCLUSIONS: The EDTA-extracted teeth demonstrated significantly lower pulp/dentin regenerative potential compared with the GdnHCl-extracted teeth. The EDTA soluble chemical components when reconstituted with the physical structure of autoclaved teeth serve as an inductive microenvironment for pulp/dentin regeneration, promoting cell proliferation, migration, and odontoblastic differentiation. PMID- 27387979 TI - FRAP to Characterize Molecular Diffusion and Interaction in Various Membrane Environments. AB - Fluorescence recovery after photobleaching (FRAP) is a standard method used to study the dynamics of lipids and proteins in artificial and cellular membrane systems. The advent of confocal microscopy two decades ago has made quantitative FRAP easily available to most laboratories. Usually, a single bleaching pattern/area is used and the corresponding recovery time is assumed to directly provide a diffusion coefficient, although this is only true in the case of unrestricted Brownian motion. Here, we propose some general guidelines to perform FRAP experiments under a confocal microscope with different bleaching patterns and area, allowing the experimentalist to establish whether the molecules undergo Brownian motion (free diffusion) or whether they have restricted or directed movements. Using in silico simulations of FRAP measurements, we further indicate the data acquisition criteria that have to be verified in order to obtain accurate values for the diffusion coefficient and to be able to distinguish between different diffusive species. Using this approach, we compare the behavior of lipids in three different membrane platforms (supported lipid bilayers, giant liposomes and sponge phases), and we demonstrate that FRAP measurements are consistent with results obtained using other techniques such as Fluorescence Correlation Spectroscopy (FCS) or Single Particle Tracking (SPT). Finally, we apply this method to show that the presence of the synaptic protein Munc18-1 inhibits the interaction between the synaptic vesicle SNARE protein, VAMP2, and its partner from the plasma membrane, Syn1A. PMID- 27387981 TI - Atomistic Insight into Tetraalkylphosphonium Bis(oxalato)borate Ionic Liquid/Water Mixtures. 2. Volumetric and Dynamic Properties. AB - Atomistic molecular dynamics simulations have been performed to investigate volumetric quantities and dynamic properties of binary trihexyltetradecylphosphonium bis(oxalato)borate ([P6,6,6,14][BOB]) ionic liquid (IL)/water mixtures with different water concentrations. The predicted liquid densities for typical [P6,6,6,14][BOB] IL/water mixtures are consistent with available experimental data with a relative discrepancy of less than 3%. The liquid densities and excess molar volumes of all studied [P6,6,6,14][BOB] IL/water mixtures are characterized by concave and convex features, respectively, within full water concentration range. The dynamic properties of [P6,6,6,14] cations, [BOB] anions, and water molecules are particularly analyzed through calculation of velocity autocorrelation functions, diffusion coefficients, and reorientational autocorrelation functions and correlation times. The translational and reorientational mobilities of three species become faster upon increasing water concentration in [P6,6,6,14][BOB] IL/water mixtures and present complex dynamical characteristics arising from three distinct microscopic diffusion features within the full water concentration range. The obtained striking volumetric quantities and particular dynamic properties are well correlated to microscopic liquid structural organization and distinct local ionic environment of all studied [P6,6,6,14][BOB] IL/water mixtures. PMID- 27387983 TI - Non-invasive follicular thyroid neoplasm with papillary-like nuclei: reducing overtreatment by reclassifying an indolent variant of papillary thyroid cancer. PMID- 27387982 TI - Prostate-specific membrane antigen (PSMA)-mediated laminin proteolysis generates a pro-angiogenic peptide. AB - Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase expressed in a number of tissues. PSMA participates in various biological functions depending on the substrate available in the particular tissue; in the brain, PSMA cleaves the abundant neuropeptide N-acetyl-aspartyl glutamate to regulate release of key neurotransmitters, while intestinal PSMA cleaves polyglutamated peptides to supply dietary folate. PSMA expression is also progressively upregulated in prostate cancer where it correlates with tumor progression as well as in tumor vasculature, where it regulates angiogenesis. The previous research determined that PSMA cleavage of small peptides generated via matrix metalloprotease-mediated proteolysis of the extracellular matrix protein laminin potently activated endothelial cells, integrin signaling and angiogenesis, although the specific peptide substrates were not identified. Herein, using enzymatic analyses and LC/MS, we unequivocally demonstrate that several laminin-derived peptides containing carboxy-terminal glutamate moieties (LQE, IEE, LNE) are bona fide substrates for PSMA. Subsequently, the peptide products were tested for their effects on angiogenesis in various models. We report that LQ, the dipeptide product of PSMA cleavage of LQE, efficiently activates endothelial cells in vitro and enhances angiogenesis in vivo. Importantly, LQE is not cleaved by an inactive PSMA enzyme containing an active site mutation (E424S). Endothelial cell activation by LQ was dependent on integrin beta-1-induced activation of focal adhesion kinase. These results characterize a novel PSMA substrate, provide a functional rationale for the upregulation of PSMA in cancer cells and tumor vasculature and suggest that inhibition of PSMA could lead to the development of new angiogenic therapies. PMID- 27387980 TI - MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients. AB - BACKGROUND: Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. RESULTS: As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. CONCLUSION: This work adds to the genotype-phenotype correlation of MYH7 relatedmyopathies confirming the complexity of the disorder. PMID- 27387984 TI - Could molecular pathology testing in lung cancer be more cost-effective? AB - AIMS: EGFR and ALK analysis is routinely undertaken prior to targeted treatment of non-squamous non-small cell lung carcinoma (NSCLC). Increasingly, limited resources require molecular pathology services to be cost-effective without detriment to patient care. METHODS: Data from an audit of molecular pathology testing in the South East Scotland Cancer Network (SCAN) network have been used to explore different testing strategies with the aim of reducing costs; including investigation of thyroid transcription factor 1 (TTF1) expression as a negative predictor for EGFR mutations. RESULTS: TTF1 immunohistochemistry had a high negative predictive value for EGFR mutations (99%). Reflex testing all non squamous NSCLC, as expected, had the highest costs, whereas limiting testing to those who might be considered for treatment would lead to a cost reduction of only 7.5%; however, a serial testing model could save 32.7%. CONCLUSIONS: Testing only patients being considered for EGFR and ALK inhibitors represented small savings; more significant savings would be achievable if testing algorithms used known associations between clinical biomarkers. PMID- 27387985 TI - Haemoglobinopathies that occur with decreased HbA2 levels: a gene mutation set involving the delta gene at a Spanish centre. AB - AIMS: Haemoglobin A2 (HbA2) consists of two globin chains, alpha and beta. Alterations in any of these genes influences the level of HbA2. Here, we present cases of structural Hb variants and thalassaemias which present either alone or together and reduce the level of HbA2 at varying degrees. Furthermore, we present a novel structural mutation in the delta globin gene, called Hb A2-Madrid. METHODS: The levels of HbA2 and HbF and the different haemoglobin variants were measured and analysed by ion exchange high performance liquid chromatography (HPLC, VARIANT II), the types of haemoglobins were determined by capillary zone electrophoresis (CZE) (Sebia) and the globin chains were determined by reversed phase HPLC. Genetic analysis was performed by automatic sequencing of the alpha and delta genes as well as by multiple PCRs for the alpha globin genes. RESULTS: In alpha thalassaemia (n=94), the HbA2 levels ranged from 1.39% to 2.43%. Among individuals with delta thalassaemia (n=5), the HbA2 level of those with delta+ thalassaemia was 1.77%, and that of those with delta0 thalassaemia was 1.70%. Among the individuals with deltabeta thalassaemia (n=13), those who were homozygous lacked HbA2. All structural haemoglobinopathies (n=97) were heterozygous; the alpha chain variants (n=84) presented with an HbA2 level of 1.76%, while the delta chain variants (n=13) presented with a level of 1.75%. CONCLUSION: HbA2 is an essential parameter in the diagnostics of haemoglobinopathies. HPLC-EC and CZE allow the quantification of HbA2. Here, we show that quantification of HbA2 is critical for the identification of alpha, delta and betadelta thalassaemias. Structural variants are discovered by HPLC. Molecular genetics is required for the proper identification of the mutations. Only with this knowledge is genetic counselling possible. PMID- 27387986 TI - Extranodal extension of lymph node metastasis is a marker of poor prognosis in oesophageal cancer: a systematic review with meta-analysis. AB - The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered as eligible. Data were summarised using risk ratios (RRs) for number of deaths/recurrences and HRs together with 95% CIs for time-dependent risk related to ENE+, adjusted for potential confounders. Fourteen studies were selected; they followed-up 1437 patients with oesophageal cancer for a median follow-up of 39.4 months. The presence of ENE was associated with a significantly increased risk of all-cause mortality (RR=1.33; 95% CI 1.18 to 1.50, p<0.0001, I2=49%; HR=2.72, 95% CI 2.03 to 3.64, p<0.0001, I2=0%), cancer-specific mortality (RR=1.35; 95% CI 1.14 to 1.59, p=0.001, I2=57%; HR=1.97, 95% CI 1.41 to 2.75, p<0.0001, I2=41%) and of risk of recurrence (RR=1.50, 95% CI 1.20 to 1.88, p<0.0001, I2=9%; HR=2.27, 95% CI 1.72 to 2.90, p<0.0001, I2=0%). On the basis of these results, in oesophageal cancer, ENE should be considered from the gross sampling to the pathology report, and in future oncological staging system. PMID- 27387987 TI - Single thyroid tumour showing multiple differentiated morphological patterns and intramorphological molecular genetic heterogeneity. AB - AIMS: A 49-year-old man presented with a single thyroid tumour that showed a combination of conventional papillary carcinoma, follicular variant of papillary carcinoma, clear cell papillary carcinoma, columnar cell carcinoma and poorly differentiated carcinoma. As all of the morphologies have been associated with papillary carcinoma in the literature, we wished to determine if they contained identical or different molecular abnormalities. METHODS: Targeted next generation sequencing (NGS) of each morphological component and metastases was performed. RESULTS: NGS revealed a BRAF p.K601E mutation in both the clear cell papillary carcinoma and poorly differentiated carcinoma and a KRAS p.G12R mutation in the papillary carcinoma, follicular variant. Two different areas of columnar cell variant were tested, with one showing a KRAS p.G12D mutation but no mutation in the other area. A KRAS p.G12R mutation was seen in the metastatic clear cell variant. Two different lymph nodes had metastatic columnar cell carcinoma, one negative for mutations but the other with a compound KRAS p.G12R and KRAS p.G12V mutation on different alleles. No mutations including BRAF and KRAS were seen in the conventional papillary carcinoma. CONCLUSIONS: Although all of the morphological patterns in this tumour have been reported as having aetiological or other association with one another, there was only partial concordance with their molecular signatures. There was significant molecular discordance, however, even with identical morphologies. PMID- 27387988 TI - Assessment of myeloid and monocytic dysplasia by flow cytometry in de novo AML helps define an AML with myelodysplasia-related changes category. AB - AIMS: In recent years, multiparameter flow cytometry has been increasingly recognised as an important tool in diagnosis of myelodysplastic syndrome and acute myeloid leukaemia (AML). Assessment of myeloid and monocytic 'immunophenotypic' dysplasia by flow cytometry in de novo AML has not been evaluated. METHODS: 97 cases of de novo AML cases were identified and reviewed by three hematopathologists. 'Immunophenotypic' dysplasia was assessed on blasts, monocytes and granulocytes by mean fluorescence intensity. RESULTS: Using the 2008 WHO classification criteria, there were 53 AML-not otherwise specified (NOS) (55%) and 28 AML with myelodysplasia-related changes (AML-MRC) (29%), while 16 cases were ambiguous as to AML-MRC status due to limited maturing cells for morphologic but adequate events number for immunophenotypic evaluation (AML-not evaluable, 16%). Compared with AML-NOS, granulocytic cells in AML-MRC had higher CD33 expression but lower CD45, CD11b and CD15. Monocytes in AML-MRC had lower expression of CD14, CD56 and CD45. Morphologic dysplasia was associated with significantly lower granulocytic forward scatter, side scatter and CD10 but higher CD33 expression. CONCLUSIONS: Our results suggest that the workup of AML cases should include flow cytometric assessment of granulocytes and monocytes. This analysis can aid a morphologic impression of multilineage dysplasia in distinguishing AML-MRC from AML-NOS, especially in cases with limited maturing myeloid cells. PMID- 27387989 TI - 70-kDa Heat Shock Protein Downregulates Dynamin in Experimental Stroke: A New Therapeutic Target? AB - BACKGROUND AND PURPOSE: The 70-kDa heat shock protein (Hsp70) protects brain cells in models of cerebral ischemia. Proteomic screening of mice subjected to middle cerebral artery occlusion identified dynamin as a major downregulated protein in Hsp70-overexpressing mice (Hsp70 transgenic mice). Dynamin-1 is expressed in neurons and participates in neurotransmission, but also transports the death receptor Fas to the cell surface, where it can be bound by its ligand and lead to apoptosis. METHODS: Mice were subjected to distal middle cerebral artery occlusion. Neuro-2a cells were subjected to oxygen glucose deprivation. Hsp70 transgenic and Hsp70-deficient (Hsp70 knockout) mice were compared with wild-type mice for histological and behavioral outcomes. Some mice and neuro-2a cell cultures were given dynasore, a dynamin inhibitor. RESULTS: Hsp70 transgenic mice had better outcomes, whereas Hsp70 knockout mice had worse outcomes compared with wild-type mice. This correlated with decreased and increased dynamin expression, respectively. Dynamin colocalized to neurons and Fas, with higher Fas levels and increased caspase-8 expression. Hsp70 induction in neuro-2a cells was protected from oxygen glucose deprivation, while downregulating dynamin and Fas expression. Further, dynamin inhibition was found to be neuroprotective. CONCLUSIONS: Dynamin may facilitate Fas-mediated apoptotic death in the brain, and Hsp70 may protect by preventing this trafficking. Dynamin should be explored as a new therapeutic target for neuroprotection. PMID- 27387990 TI - Care Received by Elderly US Stroke Survivors May Be Underestimated. AB - BACKGROUND AND PURPOSE: Previous studies exploring stroke-related caregiving focused solely on informal caregiving and a relatively limited set of activities. We sought to determine whether, and at what cost, stroke survivors receive more care than matched controls using an expanded definition of caregiving and inclusion of paid caregivers. METHODS: Data were drawn from the National Health and Aging Trends Study (NHATS), a nationally representative survey of Medicare beneficiaries. NHATS personnel conducted in-person interviews with respondents or proxies to determine the weekly hours of care received. We compared hours of assistance received between self-reported stroke survivors (n=892) and demography and comorbidity-matched nonstroke controls (n=892). The annual cost of stroke caregiving was estimated using reported paid caregiving data and estimates of unpaid caregiving costs. RESULTS: Of community-dwelling elderly stroke survivors, 51.4% received help from a caregiver. Stroke survivors received an average of 10 hours of additional care per week compared with demography- and comorbidity matched controls (22.3 hours versus 11.8 hours; P<0.01). We estimate that the average annual cost for caregiving for an elderly stroke survivor is ~$11 300 or ~$40 billion annually, for all elderly stroke survivors, of which $5000 per person, or $18.2 billion annually, is specific to stroke. CONCLUSIONS: Although stroke survivors are known to require considerable caregiving resources, our findings suggest that previous assessments may underestimate hours of care received and hence costs. PMID- 27387992 TI - Letter by Tsuda Regarding Article, "Obstructive Sleep Apnea in Acute Stroke: A Role for Systemic Inflammation". PMID- 27387991 TI - Diabetes Mellitus Impairs Cognitive Function in Middle-Aged Rats and Neurological Recovery in Middle-Aged Rats After Stroke. AB - BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is a common metabolic disease among the middle-aged and older population, which leads to an increase of stroke incidence and poor stroke recovery. The present study was designed to investigate the impact of DM on brain damage and on ischemic brain repair after stroke in aging animals. METHODS: DM was induced in middle-aged rats (13 months) by administration of nicotinamide and streptozotocin. Rats with confirmed hyperglycemia status 30 days after nicotinamide-streptozotocin injection and age matched non-DM rats were subjected to embolic middle cerebral artery occlusion. RESULTS: Middle-aged rats subjected to nicotinamide-streptozotocin injection became hyperglycemic and developed cognitive deficits 2 months after induction of DM. Histopathologic analysis revealed that there was sporadic vascular disruption, including cerebral microvascular thrombosis, blood-brain barrier leakage, and loss of paravascular aquaporin-4 in the hippocampi. Importantly, middle-aged DM rats subjected to stroke had exacerbated sensorimotor and cognitive deficits compared with age-matched non-DM ischemic rats during stroke recovery. Compared with age-matched non-DM ischemic rats, DM ischemic rats exhibited aggravated neurovascular disruption in the bilateral hippocampi and white matter, suppressed stroke-induced neurogenesis and oligodendrogenesis, and impaired dendritic/spine plasticity. However, DM did not enlarge infarct volume. CONCLUSIONS: Our data suggest that DM exacerbates neurovascular damage and hinders brain repair processes, which likely contribute to the impairment of stroke recovery. PMID- 27387993 TI - Response by Ifergane et al to Letter Regarding Article, "Obstructive Sleep Apnea in Acute Stroke: A Role for Systemic Inflammation". PMID- 27387994 TI - Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events: Findings From ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48). AB - BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with versus without previous IS/TIA. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio, 2.0-3.0; median time-in-therapeutic range, 68.4%) versus once-daily edoxaban (higher-dose edoxaban regimen [HDER], 60/30 mg; lower-dose edoxaban regimen, 30/15 mg) with 2.8-year median follow-up. Primary end points included all stroke/systemic embolic events (efficacy) and major bleeding (safety). Because only HDER is approved, we focused on the comparison of HDER versus warfarin. RESULTS: Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were >=75 years. Compared with 15 132 without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; P<0.001; major bleeding 3.03% versus 2.64% per year; P<0.001; intracranial hemorrhage, 0.70% versus 0.40% per year; P<0.001). Among patients with previous IS/TIA, annualized intracranial hemorrhage rates were lower with HDER than with warfarin (0.62% versus 1.09%; absolute risk difference, 47 [8-85] per 10 000 patient-years; hazard ratio, 0.57; 95% confidence interval, 0.36-0.92; P=0.02). No treatment subgroup interactions were found for primary efficacy (P=0.86) or for intracranial hemorrhage (P=0.28). CONCLUSIONS: Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding. HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391. PMID- 27387996 TI - Structural and compositional changes of dissolved organic matter upon solid-phase extraction tracked by multiple analytical tools. AB - Although PPL-based solid-phase extraction (SPE) has been widely used before dissolved organic matter (DOM) analyses via advanced measurements such as ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), much is still unknown about the structural and compositional changes in DOM pool through SPE. In this study, selected DOM from various sources were tested to elucidate the differences between before and after the SPE utilizing multiple analytical tools including fluorescence spectroscopy, FT-ICR-MS, and size exclusion chromatography with organic carbon detector (SEC-OCD). The changes of specific UV absorbance indicated the decrease of aromaticity after the SPE, suggesting a preferential exclusion of aromatic DOM structures, which was also confirmed by the substantial reduction of fluorescent DOM (FDOM). Furthermore, SEC-OCD results exhibited very low recoveries (1-9 %) for the biopolymer fraction, implying that PPL needs to be used cautiously in SPE sorbent materials for treating high molecular weight compounds (i.e., polysaccharides, proteins, and amino sugars). A careful examination via FT-ICR-MS revealed that the formulas lost by the SPE might be all DOM source-dependent. Nevertheless, the dominant missing compound groups were identified to be the tannins group with high O/C ratios (>0.7), lignins/carboxyl-rich alicyclic molecules (CRAM), aliphatics with high H/C >1.5, and heteroatomic formulas, all of which were prevailed by pseudo analogous molecular formula families with different methylene (-CH2) units. Our findings shed new light on potential changes in the compound composition and the molecular weight of DOM upon the SPE, implying precautions needed for data interpretation. Graphical Abstract Tracking the characteristics of DOM from various origins upon PPL-based SPE utilizing EEMPARAFAC, SEC-OCD, and FT-ICR-MS. PMID- 27387995 TI - Computational study of the inhibitory mechanism of the kinase CDK5 hyperactivity by peptide p5 and derivation of a pharmacophore. AB - The hyperactivity of the cyclic dependent kinase 5 (CDK5) induced by the activator protein p25 has been linked to a number of pathologies of the brain. The CDK5-p25 complex has thus emerged as a major therapeutic target for Alzheimer's disease (AD) and other neurodegenerative conditions. Experiments have shown that the peptide p5 reduces the CDK5-p25 activity without affecting the endogenous CDK5-p35 activity, whereas the peptide TFP5, obtained from p5, elicits similar inhibition, crosses the blood-brain barrier, and exhibits behavioral rescue of AD mice models with no toxic side effects. The molecular basis of the kinase inhibition is not currently known, and is here investigated by computer simulations. It is shown that p5 binds the kinase at the same CDK5/p25 and CDK5/p35 interfaces, and is thus a non-selective competitor of both activators, in agreement with available experimental data in vitro. Binding of p5 is enthalpically driven with an affinity estimated in the low uM range. A quantitative description of the binding site and pharmacophore is presented, and options are discussed to increase the binding affinity and selectivity in the design of drug-like compounds against AD. PMID- 27387998 TI - [Not Available]. PMID- 27387997 TI - Comparisons of GFR estimation using the CKD Epidemiology Collaboration (CKD-EPI) equation and other creatinine-based equations in Asian population: a systematic review. AB - PURPOSE: The aim of the study was to summarize the evidence of the validation of CKD-EPI equation and alternative creatinine-based equations in Asian population. METHODS: Relevant validation studies of CKD-EPI and other creatinine-based equations were identified by a systematic literature searching of PubMed conducted from January 2009 through August 2014. Searching terms included "CKD EPI", "Kidney function test [MeSH] and validation", and "Glomerular filtration rate [MeSH] and validation" without language or design of study restrictions. The quality of each study was assessed using Quality Assessment of diagnostic Accuracy studies-2 tool. RESULTS: Of 1064 studies identified, 10 studies were included in the present systematically review. The CKD-EPI equation has been validated in several Asian population including Thai, Japanese, Chinese, Taiwanese, Pakistani as well as Arabic. CKD-EPI equation met the clinically significant 75 % P30 value in several populations, although corrections of some factors may increase the accuracy of the equation. However, some populations may need to find more accurate equations or methods to estimate GFR for the patients. CONCLUSIONS: CKD-EPI is a good equation to start with for estimation of patients' renal function but for certain disease states and racial populations, the CKD-EPI should be validated before applying. More research is needed in order to develop validated eGFR equations for specific populations and to improve upon the accuracies of currently acceptable equations to better guide therapy and improve patient outcomes. PMID- 27388000 TI - [Not Available]. PMID- 27387999 TI - [Not Available]. PMID- 27388001 TI - [Not Available]. PMID- 27388003 TI - [Not Available]. PMID- 27388002 TI - [Not Available]. PMID- 27388004 TI - [Not Available]. PMID- 27388005 TI - [Not Available]. PMID- 27388006 TI - Acute bacterial prostatitis and abscess formation. AB - BACKGROUND: The purpose of this study was to identify risk factors for abscess formation in acute bacterial prostatitis, and to compare treatment outcomes between abscess group and non-abscess group. METHODS: This is a multicenter, retrospective cohort study. All patients suspected of having an acute prostatic infection underwent computed tomography or transrectal ultrasonography to discriminate acute prostatic abscesses from acute prostatitis without abscess formation. RESULTS: A total of 31 prostate abscesses were reviewed among 142 patients with acute prostatitis. Univariate analysis revealed that symptom duration, diabetes mellitus and voiding disturbance were predisposing factors for abscess formation in acute prostatitis. However, diabetes mellitus was not related to prostate abscess in multivariate analysis. Patients with abscesses <20 mm in size did not undergo surgery and were cured without any complications. In contrast, patients with abscesses >20 mm who underwent transurethral resection had a shorter duration of antibiotic treatment than did those who did not have surgery. Regardless of surgical treatment, both the length of hospital stay and antibiotic treatment were longer in patients with prostatic abscesses than they were in those without abscesses. However, the incidence of septic shock was not different between the two groups. A wide spectrum of microorganisms was responsible for prostate abscesses. In contrast, Escherichia coli was the predominant organism responsible for acute prostatitis without abscess. CONCLUSION: Imaging studies should be considered when patients with acute prostatitis have delayed treatment and signs of voiding disturbance. Early diagnosis is beneficial because prostatic abscesses require prolonged treatment protocols, or even require surgical drainage. Surgical drainage procedures such as transurethral resection of the prostate were not necessary in all patients with prostate abscesses. However, surgical intervention may have potential merits that reduce the antibiotic exposure period and enhance voiding function in patients with prostatic abscess. PMID- 27388007 TI - Prevalence and intensity of genito-urinary schistosomiasis and associated risk factors among junior high school students in two local government areas around Zobe Dam in Katsina State, Nigeria. AB - BACKGROUND: The national burden of genito-urinary schistosomiasis in Nigeria has been expressed by an estimate of 101.3 million people at risk with an alarming figure of 29 million infected. Report obtained from respondents about Praziquantel(r) distribution and the obviously prevalent haematuria without any control programme in place justified the need for data on the prevalence, intensity of infection and associated risk factors which were the objectives this cross-sectional survey sought to address. METHODS: A total of 718 students aged 10-23 years from the study area were surveyed between May and August, 2015. Data on socio-demographic and risk factors were obtained using structured questionnaires. Clean universal bottles with corresponding labels were offered for sample collection between 10:00 am and 13:30 pm. Centrifuged samples were microscopically examined and intensity of infection was recorded per 10 ml of each sample. RESULTS: Prevalence of genito-urinary schistosomiasis was 22.7 % with a mean intensity of 25.05 (+/- standard deviation, +/- 71.51) eggs/10 ml of urine. Higher prevalence (19.5 %) and mean intensity (28.7 eggs/10 ml of urine) was recorded among boys. Sex (chi (2) = 77.065, P < 0.0001), age group 16-18 (chi (2) = 5.396, P = 0.0202), altitude (chi (2) = 8.083, P = 0.0045), unwholesome water sources (chi (2) = 27.148, P < 0.0001), human recreational activities (chi (2) = 122.437, P < 0.0001), mothers' occupation (chi (2) = 6.359, P = 0.0117), farming (chi (2) = 6.201, P = 0.0128) and other brown collar jobs (chi (2) = 4.842, P = 0.0278) in fathers' occupational category were found to be significantly associated with urogenital schistosomiasis. Boys were seven times more likely to be infected compared to girls [AOR (95 % CI): 7.3 (4.26-12.4)]. Age group 16-18 years was four times more likely to be infected compared to age group 10-12 years [AOR (95 % CI): 4.43 (2.62-7.49)]. Similarly, respondents with farming as fathers' occupation were twice more likely to be infected than those whose fathers were civil servants [AOR (95 % CI): 2.08 (1.2-3.59)]. CONCLUSIONS: Dutsin-Ma and Safana were classified as moderate-risk Local Government Areas (LGA). Sex, altitude, unwholesome water sources and mothers' occupation were identified as the determining epidemiological factors in the prevalence of the disease. Sustainable chemotherapeutic intervention with Praziquantel(r), good network of treated pipe-borne water, health education and waste disposal facilities are highly recommended to reduce its prevalence below the threshold of public health significance. PMID- 27388008 TI - Predictive factors for a long-term response duration in non-squamous cell lung cancer patients treated with pemetrexed. AB - BACKGROUND: Pemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). However, factors that can predict the benefits of pemetrexed therapy have not yet been defined. METHODS: We compared the clinical and molecule pathological characteristics of good and poor responders among a cohort of 1,848 non-squamous NSCLC patients who had received at least two cycles of pemetrexed therapy between November 2006 and February 2015. Among these cases, 92 good responders who were the top 5 % in terms of progression-free survival (PFS) and 222 poor responders who had progressive disease after only 2 cycles of therapy were selected for the analysis. RESULTS: The median PFS of the good responders was 29.9 months (range; 20.9-90.0) and the median number of cycle was 37 (range; 18-129). Although 53.5 % of patients showed stable disease (SD), this response was sustained (median PFS in SD, 29.6 months). A never-smoking status was related to better survival outcome, whereas EGFR mutation, two or more metastatic sites, and intra-abdominal metastasis were each associated with a poor PFS. ALK translocation showed a tendency for a positive impact on response to pemetrexed, whereas metastatic lesion to liver, adrenal gland or bone showed a tendency for a negative impact despite not reaching our threshold for statistical significance. CONCLUSIONS: Predictive factors, such as smoking status, the status of genetic alteration and tumor burden, should be considered when administering pemetrexed therapy for non-squamous NSCLC. PMID- 27388009 TI - The uses and outcomes of the Martius fat pad in female urology. AB - PURPOSE: To assess the indications, morbidity, efficacy and outcomes of Martius fat pad (MFP) interposition in reconstructive female urology. MATERIALS AND METHODS: Data on 159 women with MFP interposition as part of their primary procedure between 2 September 2005 and 2 July 2015 were prospectively collected. Patient demographics and the indications for MFP interposition along with the outcomes of their primary procedures and short- and long-term complications related to the MFP, along with patient reported perception of post-operative appearance, were noted. RESULTS: The main indications for MFP interposition were urethral diverticulum excision (74), vaginal repair of vesicovaginal fistula (VVF) (43), removal and repair of urethral erosion of mid-urethral tape (MUT) (24), female urethroplasty for stricture (12), vaginal closure of bladder neck for complex end-stage stress urinary incontinence (USUI) (4) and as a MUT wrap for protection of urethra and vagina in women with fragile urethras (2). The majority of patients (127 or 79 %) rated the post-operative appearance of their labia as good or excellent. Only 1 patient (0.6 %) felt the post-operative appearance was unsatisfactory. There were 2 post-harvest labial haematoma (1.25 %), 1 labial wound infection in an overweight diabetic patient (0.6 %) and no other significant short- or long-term complications. CONCLUSIONS: MFP interposition is associated with good cosmesis and a very low complication rate (<2 %). It appears to lower new onset post-procedure USUI, prevent erosion in the 'fragile' urethra and improve outcomes following repair of post-surgery VVF/UVF. MFP is a versatile and effective tool in the female urologists' armamentarium. PMID- 27388010 TI - Comprehensive Identification and Quantitation of Basic Building Blocks for Low Molecular Weight Heparin. AB - Low-molecular weight heparins (LMWHs) are widely used anticoagulant drugs. They inherit the heterogeneous backbone sequences of the parent heparin, while the chemical depolymerization process modifies the nonreducing end (NRE) and reducing end (RE) of their sugar chains. Some side reactions may also occur and increase the structural complexity of LMWHs. It is important to precisely characterize the structures of LMWHs, especially their chemical modifications, to ensure drug quality and safety. Compositional analysis provides a powerful approach to reveal the building blocks that make up the LMWHs, which are the mutual consequence of the heparin starting materials and the manufacturing process. Here, we introduce a comprehensive analytical method to recover the most basic building blocks of LMWHs. A strategy of combining both enzymatic digestion and oxidative degradation of LMWH was used to make the NRE, RE, and backbone structures differentiable from one another. Satisfactory separation, identification, and quantitation were achieved by coupling hydrophilic interaction chromatography with a triple quadrupole mass spectrometer operating under the multiple reaction monitoring mode. After enzymatic digestion, over 30 species were detected, with both natural and chemically modified heparin basic building blocks. Two novel structures, including a trisaccharide containing two glucosamine residues and a tetrasaccharide containing a 3-O-sulfated uronic acid residue, were discovered. Reduced and oxidatively degraded samples were analyzed to provide the complementary information on both termini of LMWHs. The reproducibility of this method was evaluated, and enoxaparin injections were analyzed to demonstrate the application of this method for evaluating the sameness of LMWH products. PMID- 27388011 TI - Effects of cue modality and emotional category on recognition of nonverbal emotional signals in schizophrenia. AB - BACKGROUND: Impaired interpretation of nonverbal emotional cues in patients with schizophrenia has been reported in several studies and a clinical relevance of these deficits for social functioning has been assumed. However, it is unclear to what extent the impairments depend on specific emotions or specific channels of nonverbal communication. METHODS: Here, the effect of cue modality and emotional categories on accuracy of emotion recognition was evaluated in 21 patients with schizophrenia and compared to a healthy control group (n = 21). To this end, dynamic stimuli comprising speakers of both genders in three different sensory modalities (auditory, visual and audiovisual) and five emotional categories (happy, alluring, neutral, angry and disgusted) were used. RESULTS: Patients with schizophrenia were found to be impaired in emotion recognition in comparison to the control group across all stimuli. Considering specific emotions more severe deficits were revealed in the recognition of alluring stimuli and less severe deficits in the recognition of disgusted stimuli as compared to all other emotions. Regarding cue modality the extent of the impairment in emotional recognition did not significantly differ between auditory and visual cues across all emotional categories. However, patients with schizophrenia showed significantly more severe disturbances for vocal as compared to facial cues when sexual interest is expressed (alluring stimuli), whereas more severe disturbances for facial as compared to vocal cues were observed when happiness or anger is expressed. CONCLUSION: Our results confirmed that perceptual impairments can be observed for vocal as well as facial cues conveying various social and emotional connotations. The observed differences in severity of impairments with most severe deficits for alluring expressions might be related to specific difficulties in recognizing the complex social emotional information of interpersonal intentions as compared to "basic" emotional states. Therefore, future studies evaluating perception of nonverbal cues should consider a broader range of social and emotional signals beyond basic emotions including attitudes and interpersonal intentions. Identifying specific domains of social perception particularly prone for misunderstandings in patients with schizophrenia might allow for a refinement of interventions aiming at improving social functioning. PMID- 27388012 TI - Glucose-6-phosphate dehydrogenase deficiency and reduced haemoglobin levels in African children with severe malaria. AB - BACKGROUND: Extensive studies investigating the role of host genetic factors during malaria associate glucose-6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency had been reported to associate with anti malarial drug induced with haemolytic anaemia. METHODS: A total of 301 Gabonese, Ghanaian, and Kenyan children aged 6-120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A(+)) and deficient (type A(-)) genotypes were determined by direct sequencing of the common African mutations G202A and A376G. Furthermore, multivariate analyses were executed to associate possible contributions of G6PD deficiency with baseline haemoglobin levels, parasitaemia and with severe malarial anaemia. RESULTS: Two hundred and seventy-eight children (132 females and 146 males) were successfully genotyped for G6PD variants. The overall prevalence of G6PD deficiency was 13 % [36/278; 3 % (4/132) female homozygous and 22 % (32/146) male hemizygous], 14 % (40/278) children were female heterozygous while 73 % (202/278) were G6PD normal [67 % (88/132) females and 78 % (114/146) males] individuals. Multivariate regression revealed a significant association of moderately and severely deficient G6PD genotypes with haemoglobin levels according to the baseline data (p < 0.0001; G6PD heterozygous: p < 0.0001; G6PD deficient: p = 0.009), but not with severe malarial anaemia (p = 0.66). No association of G6PD genotypes with baseline parasitaemia. CONCLUSIONS: In this study, moderately (type A(+)) and severely (type A(-)) G6PD deficiency showed significant association with lower haemoglobin concentrations at baseline in African children with severe malaria without leading to severe malarial anaemia. In addition, there was no association of G6PD variant types with parasite densities on admission. PMID- 27388014 TI - Screening of KHP30-like prophages among Japanese Helicobacter pylori strains, and genetic analysis of a defective KHP30-like prophage sequence integrated in the genome of the H. pylori strain NY40. AB - We have recently reported the active Helicobacter pylori bacteriophages (phages), KHP30 and KHP40, the genomic DNAs of which exist as episomes in host bacterial strains isolated in Japan (i.e. pseudolysogeny). In this study, we examined the possibility of the lysogeny of active KHP30-like phages in Japanese H. pylori strains, because their genomes contain a putative integrase gene. Only the NY40 strain yielded partial detection of a KHP30-like prophage sequence in PCR among 174 Japanese H. pylori isolates, except for strains producing the above active phages. Next, according to the genomic analysis of the NY40 strain, the KHP30 like prophage sequence was found to be located from ca. 524 to 549 kb in the host chromosome. The attachment sites, attL and attR, in the NY40 genome showed almost the same genomic location and sequence as those detected in a French isolate B38, suggesting that an active parental KHP30-like phage had integrated into the ancestral NY40 genome in a site-specific manner. The prophage found in the NY40 genome was assumed to have been genetically modified, after site-specific integration. These, together with the data in the KHP30-like prophages of other H. pylori genomes, suggest that the lysogenic state of the KHP30-like phages is generally unstable. PMID- 27388015 TI - Capsule of Streptococcus equi subsp. zooepidemicus hampers the adherence and invasion of epithelial and endothelial cells and is attenuated during internalization. AB - Direct interaction between pathogens and host cells often is a prerequisite for colonization, infection and dissemination. Regulated production of capsular polysaccharide (CPS), which is made of hyaluronic acid, is essential for the pathogenicity of Streptococcus equi subsp. Zooepidemicus (SEZ). Here, we constructed a CPS-deleted mutant and analyzed it along with the parental wild type strain in attachment and invasion of mammalian epithelial and endothelial cell lines. The CPS-deleted mutant exhibited significant increase in adherence and invasion by several orders of magnitude compared with the wild-type strain through quantitative analysis and electron microscopy observation. After the wild type strain was recovered from invaded cells, its morphology was analyzed by visual methods and scanning electron microscopy, which revealed that its capsule was almost completely absent. Capsule measurements showed a similar result in which CPS production was nearly attenuated to the same extent as in the CPS deleted mutant. qPCR assays revealed a marked reduction in the transcriptional levels of the CPS biosynthesis genes, has operon. Moreover, the repression in capsular production was stable inheritance. Our findings indicate that SEZ is a facultative intracellular bacterium, capsule attenuation in SEZ contributes to attachment and invasion in interactions with host cells, and the active regulation of capsule breakdown is controlled by SEZ during internalization. PMID- 27388017 TI - Age trends of genetic parameters, early selection and family by site interactions for growth traits in Larix kaempferi open-pollinated families. AB - BACKGROUND: Japanese larch (Larix kaempferi) as a successful exotic species has become one of the most important economic and ecological conifers in China. In order to broaden the genetic resource of Larix kaempferi, an effort was made in 1996 to introduce 128 families from seven seed orchards in Japan, with which to establish two progeny trials in climatically different environments. The experiment was aimed to determine the strategy of early selection, particularly important for long-rotated Japanese larch, and the optimal breeding program for specific environments. RESULT: Growth trajectories revealed different growth performances of stem height (HGT) and diameter at breast height (DBH) in two different environments, Hubei and Liaoning. In both sites, there were marked variabilities in HGT, DBH and volume (VOL) among families at each year. The trends of individual and family heritability and age-age correlations were found to follow a certain dynamic pattern. Based on these trends, the optimum selection age was determined at four years for HGT and five years for DBH in Hubei and Liaoning. Genetic gains for VOL were 34.4 and 6.04 % in Hubei and Liaoning respectively when selection ratio was 10 % at age 16. Type-B correlations were less than 0.67 and rank correlations of breeding value were less than 0.4 for HGT, DBH and VOL between the two sites, revealing that there exist pronounced family-by-site interactions for the growth traits of Larix kaempferi. CONCLUSIONS: Early selection for Larix kaempferi is an effective strategy to overcome its long rotation age. In early selection, dual growth trait selection is more effective than single one. Regionalization deployment should be considered in Larix. kaempferi breeding program based on different environmental factors. PMID- 27388013 TI - HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds. AB - BACKGROUND: Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design. RESULTS: Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection. The NAb response was dependent on the N332 glycan and viral resistance against the N332-glycan dependent bNAb PGT135 developed over time but viral escape did not occur at or near this glycan. In contrast, the virus likely escaped by increasing V1 length, with up to 21 amino acids, accompanied by the introduction of 1-3 additional glycans, as well as 2-4 additional cysteine residues within V1. CONCLUSIONS: In the individual studied here, HIV-1 escaped from N332-glycan directed NAb responses without changing the epitope itself, but by elongating a variable loop that shields this epitope. PMID- 27388016 TI - Prognostic and clinical impact of PIK3CA mutation in gastric cancer: pyrosequencing technology and literature review. AB - BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations that activate the PI3K/AKT signaling pathway have been observed in several types of carcinoma and have been associated with patient prognosis. However, the significance of PIK3CA mutations in gastric cancer remains unclear. This retrospective study investigated the relationship between PIK3CA mutations and clinical outcomes in patients with gastric cancer. Additionally, we reviewed the rate of PIK3CA mutations in gastric cancer and the association between PIK3CA mutations and prognosis in human cancers. METHODS: The study included 208 patients with gastric cancer who underwent surgical resection at Kumamoto University Hospital, Japan, between January 2001 and August 2010. Mutations in PIK3CA exons 9 and 20 were quantified by pyrosequencing assays. RESULTS: PIK3CA mutations were detected in 25 (12 %) of the 208 patients. Ten patients had c.1634A > G (p.E545G), 10 had c.1624G > A (p.E542K), 13 had c.1633G > A (p.E545K), nine had c.3139C > T (p.H1047R), and 1 had c.3140A > G (p.H1047Y) mutations. PIK3CA mutations were not significantly associated with any clinical, epidemiologic, or pathologic characteristic. Kaplan-Meier analysis showed no significant differences in disease-free survival (log rank P = 0.84) and overall survival (log rank P = 0.74) between patients with and without PIK3CA mutations. CONCLUSIONS: Mutations in PIK3CA did not correlate with prognosis in patients with gastric cancer, providing additional evidence for the lack of relationship between the two. PMID- 27388018 TI - Vertebral artery loops in surgical perspective. AB - PURPOSE: Vertebral artery loop is a congenital or acquired anomaly. Vertebral artery loops are incidentally diagnosed during evaluation of neck problems and trauma. We aimed to present the incidence of VA loops using magnetic resonance angiography in consecutive patients and discuss epidemiological data including the gender, age, location, signs and symptoms, treatment approaches and outcomes of VA loops via analyzing literature. METHODS: In the first leg of our two-legged study, consecutive patients were evaluated using magnetic resonance angiography to detect any medial loop of vertebral arteries. The study period was from October 2015 to March 2016. In the second leg, academic databases about medial loop of vertebral artery were screened. Case reports, case series, abstracts and references of relevant literature were searched manually to avoid any missing cases. RESULTS: We evaluated 239 consecutive patients using magnetic resonance angiography. Twenty-one patients were excluded from the study due to inadequate image acquisition, aplastic vertebral artery and/or concomitant vertebral artery stenosis. Medial loop of V2 vertebral artery was observed in 13 patients (5.9 %): 9 with left, 2 with right and 2 with bilateral medial V2 loop. Patients with medial V2 loop were significantly older than patients with straight vertebral arteries (70.30 vs. 62.36, p = 0.028). In the literature analysis, VA loops were more commonly observed at V2 segment (90.5 %). Vertebral artery loops were mostly diagnosed at the 5th and 6th decades of life predominantly in females. The most common signs and symptoms were radiculopathy and/or neck pain, and signs and symptoms of vertebrobasilar insufficiency. CONCLUSIONS: Concise pre-operative evaluation of the vertebral arteries is essential to avoid the injury of undiagnosed VA loops during surgery, which might result in catastrophic circumstances. Further evaluation of the vertebral arteries using MR angiography is required, especially in elder age, before cervical spine surgeries. PMID- 27388019 TI - Intervertebral disc classification by its degree of degeneration from T2-weighted magnetic resonance images. AB - PURPOSE: The primary goal of this article is to achieve an automatic and objective method to compute the Pfirrmann's degeneration grade of intervertebral discs (IVD) from MRI. This grading system is used in the diagnosis and management of patients with low back pain (LBP). In addition, biomechanical models, which are employed to assess the treatment on patients with LBP, require this grading value to compute proper material properties. MATERIALS AND METHODS: T2-weighted MR images of 48 patients were employed in this work. The 240 lumbar IVDs were divided into a training set (140) and a testing set (100). Three experts manually classified the whole set of IVDs using the Pfirrmann's grading system and the ground truth was selected as the most voted value among them. The developed method employs active contour models to delineate the boundaries of the IVD. Subsequently, the classification is achieved using a trained Neural Network (NN) with eight designed features that contain shape and intensity information of the IVDs. RESULTS: The classification method was evaluated using the testing set, resulting in a mean specificity (95.5 %) and sensitivity (87.3 %) comparable to those of every expert with respect to the ground truth. CONCLUSIONS: Our results show that the automatic method and humans perform equally well in terms of the classification accuracy. However, human annotations have inherent inter- and intra-observer variabilities, which lead to inconsistent assessments. In contrast, the proposed automatic method is objective, being only dependent on the input MRI. PMID- 27388021 TI - Proline-Mediated Transition Metal-Free Access to 1H-Indazolones from 2 Halobenzohydrazides. AB - Transition metal-free access to 1H-indazolones 1 has been achieved on the basis of base-mediated intramolecular C-N bond formation. Reactions of 2 halobenzohydrazides 2 with potassium tert-butoxide in the presence of catalytic proline provided indazolones 1 in moderate to good yields. This transformation may proceed primarily via the radical pathway according to the control experiment with a radical scavenger. PMID- 27388020 TI - The radiologic assessment of posterior ligamentous complex injury in patients with thoracolumbar fracture. AB - PURPOSES: To discuss whether radiologic parameters are closely related to posterior ligamentous complex (PLC) injury identified by magnetic resonance imaging (MRI). METHODS: One hundred and five thoracolumbar fracture (T11-L2) patients were retrospectively analyzed in the study. The patients were divided into different groups by the status of the PLC on MRI: intact, incompletely ruptured and ruptured. The radiographic parameters included the anterior edge inferior endplate angle (AEIEA), the anterior edge displacement (AED), the Cobb angle (CA), the region angle (RA), the sagittal index (SI), local kyphosis (LK), the anterior/posterior vertebral height ratio (A/P ratio), the anterior vertebral height ratio (AVH ratio), and bony fragment in front of the fractured vertebra (BFOFV). T test, Pearson's Chi-square and multivariate logistic regression were calculated for the variables. RESULTS: Supraspinous ligament (SSL) rupture versus intact was not only associated with the occurrence of AEIEA <70 degrees , LK >25 degrees and BFOFV, but also with increased AED (9.89 +/- 3.12 mm and 9.34 +/- 3.36 mm, P = 0.034), RA (9.52 +/- 3.93 degrees versus 7.91 +/- 3.99 degrees , P = 0.042), and LK (23.98 +/- 5.88 degrees versus 15.55 +/- 5.28 degrees , P = 0.021). The indications for interspinous ligament (ISL) injury included AEIEA <75 degrees , AEIEA <70 degrees (P = 0.004 and P < 0.001, respectively), increased AED (P = 0.010), LK >25 degrees (P = 0.024), AVH (P < 0.001), and BFOFV (P < 0.001). Multivariate logistic regression analysis revealed that AEIEA <70 degrees and BFOFV were high risk factors for SSL rupture [standard partial regression coefficients (betas) were 0.439 and 0.408, P = 0.003 and 0.001, respectively] and ISL rupture (betas were 0.548 and 0.494, P = 0.028 and 0.001, respectively). Increased AED and LK >25 degrees were also related to either ISL rupture (P = 0.035 and 0.001, respectively) or SSL rupture (P = 0.014 and 0.008, respectively). CONCLUSION: Our data may prove useful in a preliminary assessment of the PLC integrity based on plain radiographic imaging. We show that radiologic indications, such as AEIEA <70 degrees , BFOFV, LK >25 degrees , and increased AED, are correlated with ISL or SSL rupture, while RA, CA, SI, A/P ratio, and AVH ratio are not. PMID- 27388022 TI - Penicillin dust exposure and penicillin resistance among pharmaceutical workers in Tehran, Iran. AB - BACKGROUND: Antimicrobial resistance (AMR) adversely impacts the prevention and treatment of a wide range of infections and is considered as a serious threat to global public health. Occupational-related AMR is a neglected area of research. OBJECTIVE: To assess exposure to penicillin dust, penicillin active materials, and to report the frequency of penicillin resistance among pharmaceutical workers in Tehran, Iran. METHODS: A quasi-experimental study was conducted among workers on a penicillin production line in a pharmaceutical company (n = 60) and workers in a food producing company (n = 60). Data were collected via survey, air sampling, and throat swab. RESULTS: The mean overall concentrations of penicillin dust and penicillin active material were 6.6 and 4.3 mg/m3, respectively, in the pharmaceutical industry. Streptococcus pneumoniae (S. pneumoniae) was detected in 45% (27) individuals in the exposed group, 92.6% of which showed penicillin resistance. Resistance was significantly higher among workers in penicillin production line (p = 0.014). CONCLUSIONS: High level of AMR among workers in penicillin production line is a health risk for the workers as well as society as a whole through the spread of drug resistant micro-organisms. PMID- 27388023 TI - Functionalization of Pyrene To Prepare Luminescent Materials-Typical Examples of Synthetic Methodology. AB - Pyrene-based pi-conjugated materials are considered to be an ideal organic electro-luminescence material for application in semiconductor devices, such as organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs) and organic photovoltaics (OPVs), and so forth. However, the great drawback of employing pyrene as an organic luminescence material is the formation of excimer emission, which quenches the efficiency at high concentration or in the solid state. Thus, in order to obtain highly efficient optical devices, scientists have devoted much effort to tuning the structure of pyrene derivatives in order to realize exploitable properties by employing two strategies, 1) introducing a variety of moieties at the pyrene core, and 2) exploring effective and convenient synthetic strategies to functionalize the pyrene core. Over the past decades, our group has mainly focused on synthetic methodologies for functionalization of the pyrene core; we have found that formylation/acetylation or bromination of pyrene can selectly lead to functionalization at K-region by Lewis acid catalysis. Herein, this Minireview highlights the direct synthetic approaches (such as formylation, bromination, oxidation, and de-tert-butylation reactions, etc.) to functionalize the pyrene in order to advance research on luminescent materials for organic electronic applications. Further, this article demonstrates that the future direction of pyrene chemistry is asymmetric functionalization of pyrene for organic semiconductor applications and highlights some of the classical asymmetric pyrenes, as well as the latest breakthroughs. In addition, the photophysical properties of pyrene-based molecules are briefly reviewed. To give a current overview of the development of pyrene chemistry, the review selectively covers some of the latest reports and concepts from the period covering late 2011 to the present day. PMID- 27388024 TI - Robust Cross-Linked Stereocomplexes and C60 Inclusion Complexes of Vinyl Functionalized Stereoregular Polymers Derived from Chemo/Stereoselective Coordination Polymerization. AB - The successful synthesis of highly syndiotactic polar vinyl polymers bearing the reactive pendant vinyl group on each repeat unit, which is enabled by perfectly chemoselective and highly syndiospecific coordination polymerization of divinyl polar monomers developed through this work, has allowed the construction of robust cross-linked supramolecular stereocomplexes and C60 inclusion complexes. The metal-mediated coordination polymerization of three representative polar divinyl monomers, including vinyl methacrylate (VMA), allyl methacrylate (AMA), and N,N-diallyl acrylamide (DAA) by Cs-ligated zirconocenium ester enolate catalysts under ambient conditions exhibits complete chemoselectivity and high stereoselectivity, thus producing the corresponding vinyl-functionalized polymers with high (92% rr) to quantitative (>99% rr) syndiotacticity. A combined experimental (synthetic, kinetic, and mechanistic) and theoretical (DFT) investigation has yielded a unimetallic, enantiomorphic-site-controlled propagation mechanism. Postfunctionalization of the obtained syndiotactic vinyl functionalized polymers via the thiol-ene click and photocuring reactions readily produced the corresponding thiolated polymers and flexible cross-linked thin-film materials, respectively. Complexation of such syndiotactic vinyl-functionalized polymers with isotactic poly(methyl methacrylate) and fullerene C60 generates supramolecular crystalline helical stereocomplexes and inclusion complexes, respectively. Cross-linking of such complexes affords robust cross-linked stereocomplexes that are solvent-resistant and also exhibit considerably enhanced thermal and mechanical properties compared with the un-cross-linked stereocomplexes. PMID- 27388025 TI - Organising medication discontinuation: a qualitative study exploring the views of general practitioners toward discontinuing statins. AB - BACKGROUND: Discontinuing medications is a complex decision making process and an important medical practice. It is a tool in reducing polypharmacy, reducing health system expenditure and improving patient quality of life. Few studies have looked at how general practitioners (GPs) discontinue a medication, in agreement with the patients, from a professional perspective. Three research questions were examined in this study: when does medication discontinuation occur in general practice, how is discontinuing medication handled in the GP's practice and how do GPs make decisions about discontinuing medication? METHODS: Twenty four GPs were interviewed using a maximum variation sample strategy. Participant observations were done in three general practices, for one day each, totalling approximately 30 consultations. RESULTS: The results show that different discontinuation cues (related to the type of consultation, medical records and the patient) create situations of dissonance that can lead to the GP considering the option of discontinuation. We also show that there is a lot of ambiguity in situations of discontinuing and that some GPs trialled discontinuing as means of generating more information that could be used to deal with the ambiguity. CONCLUSIONS: We conclude that the practice of discontinuation should be conceptualised as a continually evaluative process and one that requires sustained reflection through a culture of systematically scheduled check-ups, routinely eliciting the patient's experience of taking drugs and trialling discontinuation. Some policy recommendations are offered including supporting GPs with lists or handbooks that directly address discontinuation and by developing more person centred clinical guidelines that discuss discontinuation more explicitly. PMID- 27388026 TI - Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules. AB - Implantation of drug delivery depots into or proximal to targeted tissue is an effective method to deliver anticancer drugs in a sustained localized manner. Herein, syringe-injectable polydextran aldehyde (PDA)-based bioadhesive gels are prepared that can locally deliver cytotoxins upon their hydrolytic fragmentation. Adhesive gels are formed by mixing doxorubicin (DOX)-functionalized PDA (DOX-PDA) and bovine serum albumin (BSA) using a dual-barrel syringe. Upon mixing and delivery, the DOX-PDA reacts with the cross-linker BSA as well as the extracellular matrix via imine bond formation to define the cohesive and adhesive properties of the gel, respectively. Resulting gels are mechanically rigid (~10 kPa) and adherent (adhesive stress ~ 4 kPa). Once formed, the DOX-PDA-BSA gels undergo slow hydrolytic degradation (>2 months) locally releasing free DOX and DOX-PDA as expected. Surprisingly, we found that macromolecules composed of DOX, PDA, and BSA are also released from the bulk material. These DOX-PDA-BSA macromolecules, along with free DOX and DOX-PDA conjugate, are internalized by A549 lung carcinoma cells, resulting in potent cell death. PMID- 27388027 TI - Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same? AB - OBJECTIVES: To review the pathophysiology, co-morbidities, and therapeutic options for psoriasis, psoriatic arthritis and rheumatoid arthritis in order to further understand the similarities and differences in treatment paradigms in the management of each disease. New targets for individualized therapeutic decisions are also identified with the aim of improving therapeutic outcome and reducing toxicity. SEARCH STRATEGY: Using the PubMed database, we searched literature published from 2000 to 2015 using combinations of the key words "psoriasis," "psoriatic arthritis," "rheumatoid arthritis," "pathogenesis," "immunomodulation," and "treatment." INCLUSION AND EXCLUSION CRITERIA: This was a non-systematic review and there were no formal inclusion and exclusion criteria. DATA EXTRACTION: Abstracts identified in the search were screened for relevance and articles considered appropriate evaluated further. References within these selected articles were also screened. Information was extracted from 198 articles for inclusion in this report. DATA SYNTHESIS: There was no formal data synthesis. Articles were reviewed and summarized according to disease area (psoriasis, psoriatic arthritis, and rheumatoid arthritis). HEADLINE RESULTS: The pathophysiology of psoriasis, psoriatic arthritis, and rheumatoid arthritis involves chronic inflammation mediated by pro-inflammatory cytokines. Dysfunction in integrated signaling pathways affecting different constituents of the immune system result in varying clinical features in the three diseases. Co-morbidities, including cardiovascular disease, malignancies, and non-alcoholic fatty liver disease are increased. Increased understanding of the immunopathogenesis allowed development of targeted treatments; however, despite a variety of potentially predictive genetic, protein and cellular biomarkers, there is still significant unmet need in these three inflammatory disorders. PMID- 27388028 TI - G protein-coupled receptors (GPCRs): The more the merrier. PMID- 27388030 TI - Erratum: Prevalence of airflow obstruction among ever-employed US adults aged 18 79 years by longest held occupation group: National Health and Nutrition Examination Survey 2007-2010. PMID- 27388029 TI - Mesoporous Nb2O5/SiO2 material obtained by sol-gel method and applied as adsorbent of crystal violet dye. AB - In this work, SiO2/Nb2O5 (SiNb) material was prepared using sol-gel method and employed as adsorbent for removal of crystal violet dye (CV). The material was characterized using nitrogen adsorption-desorption isotherms, FTIR spectroscopy, pHpzc, and SEM-EDS. The analysis of N2 isotherms revealed the presence of micro- and mesopores in the SiNb sample with specific surface area as high as 747 m2 g 1. For the CV adsorption process, variations of several parameters such as of pH, temperature, contact time, and concentration of dye of the process were evaluated. The optimum initial pH of the CV dye solution was 7.0. The adsorption kinetic and equilibrium data for CV adsorption were suitably represented by the general-order and Liu models, respectively. The maximum adsorption capacity of the CV dye by SiNb was achieved at 303 K, which attained 116 mg g-1 at this temperaure. Dye effluents were simulated and used to check the applicability of the SiNb material for treatment of effluents - the material showed very good efficiency for decolorization of dye effluents. PMID- 27388031 TI - Effect of heavy haze and aerosol pollution on rice and wheat productions in China. AB - In China, regional haze pollution is a serious environmental problem. The impact on ecosystem, however, is not clearly understood. This study investigates the effect of regional haze pollution on the yields of rice and wheat in China. The spatial and temporal distributions of aerosol optical depth (AOD) show high particulate pollution in the North China Plain region, Yangtze River Delta region, the central eastern China, and the Si Chuan Basin, coexisted largely with crop growth in time and space. The solar irradiance reaching these regions is estimated to reduce by up to 28-49%, calculated using the AOD distributions and tropospheric ultraviolet-visible (TUV) model. Reduction of solar irradiance in these regions can depress optimal yields of about 45% of rice and 75% of wheat growth in China, leading to 2% reduction in total rice production and 8% reduction in total wheat production in China. However, there are large uncertainties of the estimate related to the diffuse solar radiation. For high diffuse radiation case, the estimate reductions of rice and wheat decrease to 1% and 4.5%, respectively. A further detailed study is needed to clearly understand this effect to meet the growing food demand in the nation in the coming decades. PMID- 27388032 TI - Predictive value of self-rated health in pregnancy for childbirth complications, adverse birth outcomes, and maternal health. AB - OBJECTIVE: To investigate whether self-rated health (SRH) in pregnancy can predict childbirth complications, adverse birth outcomes, and maternal health problems up to 3 years after delivery. METHODS: A retrospective analysis was performed of data obtained in a prospective longitudinal population-based birth cohort study. Pregnant women resident in the Brno or Znojmo regions in the Czech Republic were included if they were expected to deliver between March 1991 and June 1992. SRH data were collected between 1991 and 1995 via pen-and-paper questionnaires administered in mid-pregnancy, and at 6 months, 18 months, and 3 years after delivery. Medical records were reviewed for pregnancy complications, childbirth complications, and birth outcomes. Multivariate regression analysis was performed. RESULTS: Overall, 4811 women were included. Better SRH in pregnancy predicted fewer childbirth complications (b=-0.03; P=0.036); lower odds of cesarean delivery (odds ratio 0.81; P=0.003); and fewer maternal health problems at 6 months (b=-0.32; P<0.001), 18 months (b=-0.28; P<0.001), and 3 years after delivery (b=-0.30; P<0.001). The effects of SRH were independent of diagnosed complications and self-reported health problems in pregnancy. CONCLUSION: SRH in pregnancy has predictive value for subsequent health outcomes, and might be an additional tool for assessment of pregnant women's health. PMID- 27388033 TI - Comparison of rapid bedside tests for phosphorylated insulin-like growth factor binding protein 1 and fetal fibronectin to predict preterm birth. AB - OBJECTIVE: To compare the accuracy of rapid bedside tests for phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP-1) and fetal fibronectin (fFN) to predict preterm delivery among women with threatened preterm labor. METHODS: A prospective observational study was conducted among women with a singleton pregnancy of 28-36 weeks, intact membranes, and symptoms suggestive of preterm labor who attended a center in New Delhi, India, between April 1, 2011, and March 31, 2014. Rapid bedside tests were performed at presentation to measure the levels of phIGFBP-1 and fFN in cervicovaginal secretions. All patients were managed as per the standard hospital protocol and followed up until delivery. RESULTS: Data were available for 468 participants. For delivery before 37 weeks, the phIGFBP-1 test exhibited a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81.1%, 97.1%, 95.2% and 87.7%, respectively. The sensitivity, specificity, PPV, and NPV for the fFN test were 19.4%, 99.4%, 97.4%, and 63.2%, respectively. The phIGFBP-1 test displayed higher sensitivity and NPV than did the fFN test for delivery before 34 weeks and within 7 days of testing (P<0.05 for all). CONCLUSION: The rapid bedside test for phIGFBP-1 was more reliable in the prediction of preterm delivery than was the equivalent test for fFN. PMID- 27388034 TI - Comparison of perinatal outcomes following fresh and frozen-thawed blastocyst transfer. AB - OBJECTIVE: To investigate the effect of ovarian stimulation on endometrial receptivity by comparing singleton pregnancy and perinatal outcomes following fresh or frozen-thawed blastocyst transfers. METHODS: A retrospective cohort study enrolled patients undergoing fresh or frozen-thawed blastocyst transfers that resulted in live deliveries between January 1, 2010 and September 30, 2013 at a single academic center. Implantation, clinical pregnancy, spontaneous abortion, and live delivery rates were calculated. The incidence of term delivery, preterm delivery, low birth weight, term low birth weight, and very low birth weight were also recorded. To detect a 10% difference in the implantation rate, a minimum sample size of at least 415 transfer cycles in each group was estimated. RESULTS: The study included data from 918 fresh and 1273 frozen-thawed cycles. Patients in both groups were of similar age and there was no difference in the grading of blastocysts. No differences were observed in the implantation (37.3% vs 37.7%), clinical pregnancy (50.2% vs 49.4%), spontaneous abortion (7.3% vs 9.3%), and live delivery (42.9% vs 40.6%) rates of the two groups. A sub analysis of all live singleton and twin deliveries revealed no difference in perinatal outcomes between the two techniques. CONCLUSIONS: The present study demonstrated equivalent singleton pregnancy and perinatal outcomes when comparing frozen-thawed and fresh blastocyst transfer procedures. PMID- 27388035 TI - Jewish ethics and xenotransplantation. AB - BACKGROUND: Although exclusively secular approaches to xenotransplantation are methodologically necessary to establish a fundamental verdict on its theoretical ethical acceptability, it is nevertheless pragmatically appropriate to take into account specifically religious positions, as religion is a factor relevant to societal acceptability. Apart from the aspect of societal acceptability, Jewish bioethics, like other religiously embedded ethics, may enrich the broader ethical discourse on xenotransplantation, as some of its principles-pikuach nefesh being the most prominent one-are plausible even in the framework of secular ethics. METHODS: This paper first explores concepts of normativity in Jewish ethics before identifying specific ethical issues in Jewish bioethics and possible resolutions offered within the framework of Jewish ethics, and then finally examine the implications for the broader debate on xenotransplantation. RESULTS: Religions in general and Judaism in specific cannot and should not be systematically excluded from ethical debates, not only because they may provide helpful input, but also because religion, religiousness and the affiliation to a religion can be crucial factors regarding the societal acceptability of specific medical technologies and procedures as they may be important aspects of an individual's identity. The principles of Jewish bioethics may be compelling to those who do not necessarily share the specifically religious prerequisites on which Jewish ethics is established. Among these rather cogent concepts is the status of natural law and naturalness, which is far more open to medical technologies and procedures deemed as unnatural and thus morally wrong by other religious parties in public discourse. CONCLUSIONS: Jewish ethics has strong tendencies toward supporting xenotransplantation given a certain criteria is met. No categorical bans on xenotransplantation can be established on the grounds of Halacha. PMID- 27388036 TI - Water molecules inside protein structure affect binding of monosaccharides with HIV-1 antibody 2G12. AB - Water molecules inside biomolecules constitute integral parts of their structure and participate in the functions of the proteins. Some of the X-ray crystallographic data are insufficient for analyzing a series of ligand-protein complexes in the same condition. We theoretically investigated antibody binding abilities of saccharide ligands and the effects of the inner water molecules of ligand-antibody complexes. Classical molecular dynamics and quantum chemical simulations using a model with possible water molecules inside the protein were performed with saccharide ligands and Human Immunodeficiency Virus 1 neutralizing antibody 2G12 complexes to estimate how inner water molecules of the protein affect the dynamics of the complexes as well as the ligand-antibody interaction. Our results indicate the fact that d-fructose's strong affinity to the antibody was partly due to the good retentiveness of solvent water molecules of the ligand and its stability of the ligand's conformation and relative position in the active site. (c) 2016 Wiley Periodicals, Inc. PMID- 27388037 TI - Surgical treatment of nasal non-melanoma skin cancer in elderly patients using dermal substitute. AB - CONCLUSIONS: The nose is often involved by non-melanoma skin cancer (NMSC) and the increase in the incidence of such tumors, the morbidity and treatment-related costs represent a significant burden to healthcare systems. A bioresorbable dermal substitute (Hyalomatrix(r)) has been used for immediate dermal coverage and nose restoration after excision of infiltrating nasal NMSCs in elderly ASA III patients. Further studies on dermal substitutes are needed to improve benefit to patients. OBJECTIVE: Surgical treatment of nasal non-melanoma skin cancer (NMSC) in elderly patients. MATERIALS AND METHODS: Ten elderly ASA III patients with nasal defects after resection of infiltrating NMSC were reconstructed in a two-stage strategy. The surgical protocol targeted an initial wide tumor excision and apposition of a dermal induction template (Hyalomatrix(r)) and successive full thickness skin autograft. Results were documented by photography, visual analog scale for patient satisfaction, and Vancouver scar scale for evaluation of final graft characteristics. RESULTS: All patients were tumor-free during the 2 years follow-up. The procedure achieved acceptable nose reshaping and graft scarring evolution. Patient satisfaction was good-to-high. PMID- 27388038 TI - Nuclear Energy Gradients for Internally Contracted Complete Active Space Second Order Perturbation Theory: Multistate Extensions. AB - We report the development of the theory and computer program for analytical nuclear energy gradients for (extended) multistate complete active space perturbation theory (CASPT2) with full internal contraction. The vertical shifts are also considered in this work. This is an extension of the fully internally contracted CASPT2 nuclear gradient program recently developed for a state specific variant by us [MacLeod and Shiozaki, J. Chem. Phys. 2015, 142, 051103]; in this extension, the so-called lambda equation is solved to account for the variation of the multistate CASPT2 energies with respect to the change in the amplitudes obtained in the preceding state-specific CASPT2 calculations, and the Z vector equations are modified accordingly. The program is parallelized using the MPI3 remote memory access protocol that allows us to perform efficient one sided communication. The optimized geometries of the ground and excited states of a copper corrole and benzophenone are presented as numerical examples. The code is publicly available under the GNU General Public License. PMID- 27388039 TI - Pharmacological interventions for treating heart failure in patients with Chagas cardiomyopathy. AB - BACKGROUND: Chagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is uncertainty regarding the efficacy and safety of pharmacological interventions for treating heart failure in people with Chagas disease. This is an update of a Cochrane review published in 2012. OBJECTIVES: To assess the clinical benefits and harms of current pharmacological interventions for treating heart failure in people with Chagas cardiomyopathy. SEARCH METHODS: We updated the searches in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (Ovid; 1946 to to February Week 1 2016), EMBASE (Ovid; 1947 to 2016 Week 07), LILACS (1982 to 15 February 2016), and Web of Science (Thomson Reuters; 1970 to 15 February 2016). We checked the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA: We included randomised clinical trials (RCTs) that assessed the effects of pharmacological interventions to treat heart failure in adult patients (18 years or older) with symptomatic heart failure (New York Heart Association classes II to IV), regardless of the left ventricular ejection fraction stage (reduced or preserved), with Chagas cardiomyopathy. We did not apply limits to the length of follow-up. Primary outcomes were all-cause mortality, cardiovascular mortality at 30 days, time-to-heart decompensation, disease-free period (at 30, 60, and 90 days), and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, 'Risk of bias' assessment and data extraction. We estimated relative risk (RR) and 95% confidence intervals (CIs) for dichotomous outcomes. We measured statistical heterogeneity using the I2 statistic. We used a fixed-effect model to synthesize the findings. We contacted authors for additional data. We developed 'Summary of findings' (SoF) tables and used GRADE methodology to assess the quality of the evidence. MAIN RESULTS: In this update, we identified one new trial. Therefore, this version includes three trials (108 participants). Two trials compared carvedilol against placebo and another assessed rosuvastatin versus placebo. All trials had a high risk of bias.Meta-analysis of two trials showed a lower proportion of all-cause mortality in the carvedilol groups compared with the placebo groups (RR 0.69; 95% CI 0.12 to 3.88, I2 = 0%; 69 participants; very low quality evidence). Neither of the trials reported on cardiovascular mortality, time-to-heart decompensation, or disease-free periods.One trial (30 participants) found no difference in hospital readmissions (RR 1.00; 95% CI 0.31 to 3.28; very low-quality of evidence) or reported adverse events (RR 0.92; 95% CI 0.67 to 1.27; very low-quality of evidence) between the carvedilol and placebo groups.There was very low-quality evidence from two trials of inconclusive effects on quality of life (QoL) between the carvedilol and placebo groups. One trial (30 participants) assessed QoL with the Minnesota Living With Heart Failure Questionnaire (21 items; item scores range from 0 to 5; a lower MLHFQ score is better). The MD was -14.74; 95% CI -24.75 to -4.73. The other trial (39 participants) measured QoL with the Medical Outcomes Study 36-item short-form health survey (SF-36; item scores range from 0 to 100; higher SF-36 score is better). Data were not provided.One trial (39 participants) assessed the effect of rosuvastatin versus placebo. The trial did not report on any primary outcomes or adverse events. There was very low-quality evidence of uncertain effects on QoL (no data were provided). AUTHORS' CONCLUSIONS: This first update of our review found very low-quality evidence for the effects of either carvedilol or rosuvastatin, compared with placebo, for treating heart failure in people with Chagas disease. The three included trials were underpowered and had a high risk of bias. There were no conclusive data to support or reject the use of either carvedilol or rosuvastatin for treating Chagas cardiomyopathy. Unless randomised clinical trials provide evidence of a treatment effect, and the trade-off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending or administering either carvedilol or rosuvastatin to treat heart failure in people with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in people with Chagas disease remains unknown. PMID- 27388040 TI - Insight into Nanoparticle Charging Mechanism in Nonpolar Solvents To Control the Formation of Pt Nanoparticle Monolayers by Electrophoretic Deposition. AB - We report on the formation of Pt nanoparticle monolayers by electrophoretic deposition from nonpolar solvents. First, the growth kinetics of Pt nanoparticles prepared by the reverse micelle technique are described in detail. Second, a model of nanoparticle charging in nonpolar media is discussed and methods to control the nanoparticle charging are proposed. Finally, essential parameters of the electrophoretic deposition process to control the deposition of nanoparticle monolayers are discussed and mechanisms of their formation are analyzed. PMID- 27388041 TI - Nuclear Countermeasure Activity of TP508 Linked to Restoration of Endothelial Function and Acceleration of DNA Repair. AB - There is increasing evidence that radiation-induced damage to endothelial cells and loss of endothelial function may contribute to both acute radiation syndromes and long-term effects of whole-body nuclear irradiation. Therefore, several drugs are being developed to mitigate the effects of nuclear radiation, most of these drugs will target and protect or regenerate leukocytes and platelets. Our laboratory has demonstrated that TP508, a 23-amino acid thrombin peptide, activates endothelial cells and stem cells to revascularize and regenerate tissues. We now show that TP508 can mitigate radiation-induced damage to endothelial cells in vitro and in vivo. Our in vitro results demonstrate that human endothelial cells irradiation attenuates nitric oxide (NO) signaling, disrupts tube formation and induces DNA double-strand breaks (DSB). TP508 treatment reverses radiation effects on NO signaling, restores tube formation and accelerates the repair of radiation-induced DSB. The radiation-mitigating effects of TP508 on endothelial cells were also seen in CD-1 mice where systemic injection of TP508 stimulated endothelial cell sprouting from aortic explants after 8 Gy irradiation. Systemic doses of TP508 that mitigated radiation-induced endothelial cell damage, also significantly increased survival of CD-1 mice when injected 24 h after 8.5 Gy exposure. These data suggest that increased survival observed with TP508 treatment may be due to its effects on vascular and microvascular endothelial cells. Our study supports the usage of a regenerative drug such as TP508 to activate endothelial cells as a countermeasure for mitigating the effects of nuclear radiation. PMID- 27388042 TI - Molecular Mechanisms of the Cardiotoxicity of the Proteasomal-Targeted Drugs Bortezomib and Carfilzomib. AB - Bortezomib and carfilzomib are anticancer drugs that target the proteasome. However, these agents have been shown to exhibit some specific cardiac toxicities by as yet unknown mechanisms. Bortezomib and carfilzomib are also being used clinically in combination with doxorubicin, which is also cardiotoxic. A primary neonatal rat myocyte model was used to study these cardiotoxic mechanisms. Exposure to submicromolar concentrations of bortezomib and carfilzomib resulted in significant myocyte damage and induced apoptosis. Both bortezomib and carfilzomib inhibited the chymotrypsin-like proteasomal activity of myocyte lysate in the low nanomolar concentration range and exhibited time-dependent inhibition kinetics. The high sensitivity of myocytes, which were determined to contain high specific levels of chymotrypsin-like proteasomal activity, to the damaging effects of bortezomib and carfilzomib was likely due to the inhibition of proteasomal-dependent ongoing sarcomeric protein turnover. A brief preexposure of myocytes to non-toxic nanomolar concentrations of bortezomib or carfilzomib greatly increased doxorubicin-mediated damage, which suggests that the combination of doxorubicin with either bortezomib or carfilzomib may produce more than additive cardiotoxicity. The doxorubicin cardioprotective agent dexrazoxane partially protected myocytes from doxorubicin plus bortezomib or carfilzomib treatment, in spite of the fact that bortezomib and carfilzomib inhibited the dexrazoxane-induced decreases in topoisomerase IIbeta protein levels in myocytes. These latter results suggest that the doxorubicin cardioprotective effects of dexrazoxane and the doxorubicin-mediated cardiotoxicity were not exclusively due to targeting of topoisomerase IIbeta. PMID- 27388043 TI - Omalizumab therapy for treatment of recalcitrant chronic spontaneous urticaria in an Asian population. AB - OBJECTIVES: There are limited data regarding omalizumab in the treatment of recalcitrant chronic spontaneous urticaria (CSU) in Asian populations. This study evaluated the effectiveness and the proper dosage of omalizumab for Asian CSU patients in a real-life setting. METHODS: We retrospectively reviewed recalcitrant CSU patients seeking treatment at the Skin Allergy Clinic, Siriraj Hospital during the 3-year period. All patients were treated with omalizumab as an add-on therapy. Standard seven-day urticaria activity score (UAS7) and medication score were used to assess omalizumab response. RESULTS: Of 13 patients, 9 patients (70%) responded well to 150 mg omalizumab injection every month, whereas 4 patients requiring updosing to 300 mg. In the 150 mg group, one patient achieved complete symptom control without antihistamine intake. Most of them required antihistamines without prednisolone and ciclosporin. Onset of omalizumab was fast, usually within the first week. Though only two patients in the 300 mg group achieved complete absence of symptoms, ciclosporin and oral corticosteroids could be discontinued. No patients reported adverse effects. CONCLUSIONS: Omalizumab at an initial dosage of 150 mg was effective in the treatment of recalcitrant CSU among Asians. Updosing to 300 mg was required to achieve satisfactory outcomes. PMID- 27388044 TI - Giardia outbreak associated with a roadside spring in Rensselaer County, New York. AB - In September 2009, the Rensselaer County Department of Health investigated an increase in Giardia duodenalis cases. The epidemiological investigation identified that a source of the illness could be a roadside spring located in the eastern part of the county. Epidemiological and environmental health staff conducted a site visit to the roadside spring and found several concerns. Water samples were collected from the roadside spring and sent to the New York State Department of Health for analysis. The water sample results indicated the presence of empty Giardia cysts. Prevention methods occurred and the roadside spring was destroyed. A total of 36 laboratory-confirmed cases of Giardia were identified from this outbreak that included residents of New York State and Massachusetts. PMID- 27388045 TI - An unusual colonic foreign body: A drosophila! PMID- 27388046 TI - The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. AB - The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-invasive electrical stimulation of this nerve through the skin may offer a simple, cost-effective alternative to the established method of vagus nerve stimulation (VNS), which requires a surgical procedure and has generated mixed results in a number of clinical trials for heart failure. This review discusses the available evidence in support of modulating cardiac activity using this strange auricular nerve. PMID- 27388047 TI - Hazardous drinking in people aged 50 years or older: a cross-sectional picture of Europe, 2011-2013. AB - OBJECTIVE: To assess gender and age differences in hazardous drinking and to analyse and compare the factors associated with it in men versus women, and in 50 to 64-year-old versus >=65-year-old people in Europe. METHODS: Cross-sectional study with data from 65,955 people aged >=50 years from 18 countries (SHARE project, 2011-2013). The outcome variable, hazardous drinking, was calculated using an adaptation of the AUDIT-C test. Several individual (sociodemographic, life-style and health factors) and contextual variables (country socioeconomic indicators and alcohol policies) were analysed. The prevalence of hazardous drinking was estimated by each exposure variable. To estimate associations, multilevel Poisson regression models with robust variance were fit, yielding prevalence ratios and their 95% confidence intervals (95%CI). RESULTS: Overall, the prevalence of hazardous drinking was 21.5% (95%CI = 21.1-22.0), with substantial differences between countries. The proportion of hazardous drinking was higher in men than in women [26.3%(95%CI = 25.6-27.1); 17.5%(95%CI = 17.0 18.0), respectively], as well as in middle-aged people than in older people [23.6%(95%CI = 23.0-24.3); 19.2%(95%CI = 18.6-19.8), respectively]. At the individual level, associations were found for migrant background, marital status, educational level, tobacco smoking, depression and self-perceived health. At the contextual level, hazardous drinking was associated with gender inequalities in society (only in women) and alcohol advertising regulations (both genders). CONCLUSIONS: One in five people aged >=50 years in the countries studied is a hazardous drinker, with large differences by countries, gender and age group. Interventions and policies aimed at preventing or reducing alcohol use in this population should account for country, gender and age differences, as well as individual characteristics. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388048 TI - Hybrid chitosan/beta-1,3-glucan matrix of bone scaffold enhances osteoblast adhesion, spreading and proliferation via promotion of serum protein adsorption. AB - Initial protein adsorption to the material surface is crucial for osteoblast adhesion, survival, and rapid proliferation resulting in intensive new bone formation. The aim of this study was to demonstrate that modification of a chitosan matrix of chitosan/hydroxyapatite (chit/HA) biomaterial for bone tissue engineering applications with linear beta-1,3-glucan (curdlan) leads to promotion of serum protein adsorption to the resultant scaffold (chit/glu/HA) and thus in enhancement of osteoblast adhesion, spreading and proliferation. Fabricated biomaterials were pre-adsorbed with different protein solutions and then protein adsorption and osteoblast behavior on the scaffolds were compared. Moreover, surface chemical composition, wettability and surface energy of biomaterials were compared. Modification of the chitosan matrix with beta-1,3-glucan introduces a greater polarpart in the resultant chitosan/beta-1,3-glucan matrix presumably resulting from more OH groups within the curdlan structure. Moreover, FTIR-ATR results suggest that there might be some sort of chemical interaction between the NH group of chitosan and the OH group of beta-1,3-glucan. As a consequence, the chit/glu/HA scaffold adsorbs significantly more adhesion proteins that are crucial for osteoblasts compared to the chit/HA material, providing a higher density culture of well-spread osteoblasts on its surface. Obtained results revealed that not only is chit/glu/HA biomaterial a promising scaffold for bone tissue engineering applications, but the specific polysaccharide chit/glu matrix itself is promising for use in the biomedical material field to modify various biomaterials in order to enhance osteoblast adhesion and proliferation on their surfaces. PMID- 27388049 TI - Quantitative Assessment of Anterior Segment Inflammation in a Rat Model of Uveitis Using Spectral-Domain Optical Coherence Tomography. AB - PURPOSE: To develop anterior segment spectral-domain optical coherence tomography (SD-OCT) and quantitative image analysis for use in experimental uveitis in rats. METHODS: Acute anterior uveitis was generated in Lewis rats. A spectral domain anterior segment OCT system was used to image the anterior chamber (AC) and ciliary body at baseline and during peak inflammation 2 days later. Customized MatLab image analysis algorithms were developed to segment the AC, count AC cells, calculate central corneal thickness (CCT), segment the ciliary body and zonules, and quantify the level of ciliary body inflammation with the ciliary body index (CBI). Images obtained at baseline and during peak inflammation were compared. Finally, longitudinal imaging and image analysis was performed over the 2-week course of inflammation. RESULTS: Spectral-domain optical coherence tomography identifies structural features of inflammation. Anterior chamber cell counts at peak inflammation obtained by automated image analysis and human grading were highly correlated (r = 0.961), and correlated well with the histologic score of inflammation (r = 0.895). Inflamed eyes showed a significant increase in average CCT (27 MUm, P = 0.02) and an increase in average CBI (P < 0.0001). Longitudinal imaging and quantitative image analysis identified a significant change in AC cell and CBI on day 2 with spontaneous resolution of inflammation by day 14. CONCLUSIONS: Spectral-domain optical coherence tomography provides high-resolution images of the structural changes associated with anterior uveitis in rats. Anterior chamber cell count and CBI determined by semi automated image analysis strongly correlates with inflammation, and can be used to quantify inflammation longitudinally in single animals. PMID- 27388050 TI - Quantitative Analysis of the Displacement of the Anterior Visual Pathway by Pituitary Lesions and the Associated Visual Field Loss. AB - PURPOSE: To evaluate quantitatively the relationship between the displacement of anterior visual pathway structures by pituitary tumors and visual field damage with the goal of improving diagnosis and management. METHODS: Subjects had pituitary macroadenomas and both magnetic resonance imaging (MRI) and static perimetry. Neuroradiologists measured the displacement of anterior visual pathway structures and right-left tumor asymmetry. To quantify the degree and laterality of visual field loss, we used algorithms from the neurologic hemifield test to analyze each right-left pair of visual fields with respect to temporal asymmetry, the proportion of loss that was temporal, total asymmetry, and total damage. We compared these metrics with the displacement of anterior visual pathway structures and tumor asymmetry. RESULTS: Of 114 subjects, 64 (56%) were male and the median age was 57 years (range, 14-88). The summation of vision loss in both eyes and the proportion of temporal loss were statistically significantly related to the maximum displacement of the anterior visual pathway (both P < 0.001 for fit of linear regression). The relationship between the asymmetry of visual field loss in the two eyes and the subjective assignment of tumor asymmetry on MRI did not achieve statistical significance (P = 0.06 by analysis of variance). CONCLUSIONS: Displacement of the anterior visual pathway by pituitary tumors is associated with both the total amount of visual field loss and the proportion of temporal visual field loss. Although there was right-left asymmetry of vision loss in some subjects, it was not related to the subjective assessment of tumor asymmetry. PMID- 27388051 TI - Dystrophin Is Required for Proper Functioning of Luminance and Red-Green Cone Opponent Mechanisms in the Human Retina. AB - PURPOSE: Visual information is processed in parallel pathways in the visual system. Parallel processing begins at the synapse between the photoreceptors and their postreceptoral neurons in the human retina. The integrity of this first neural connection is vital for normal visual processing downstream. Of the numerous elements necessary for proper functioning of this synaptic contact, dystrophin proteins in the eye play an important role. Deficiency of muscle dystrophin causes Duchenne muscular dystrophy (DMD), an X-linked disease that affects muscle function and leads to decreased life expectancy. In DMD patients, postreceptoral retinal mechanisms underlying scotopic and photopic vision and ON- and OFF-pathway responses are also altered. METHODS: In this study, we recorded the electroretinogram (ERG) while preferentially activating the (red-green) opponent or the luminance pathway, and compared data from healthy participants (n = 16) with those of DMD patients (n = 10). The stimuli were heterochromatic sinusoidal modulations at a mean luminance of 200 cd/m2. The recordings allowed us also to analyze ON and OFF cone-driven retinal responses. RESULTS: We found significant differences in 12-Hz response amplitudes and phases between controls and DMD patients, with conditions with large luminance content resulting in larger response amplitudes in DMD patients compared to controls, whereas responses of DMD patients were smaller when pure chromatic modulation was given. CONCLUSIONS: The results suggest that dystrophin is required for the proper function of luminance and red-green cone opponent mechanisms in the human retina. PMID- 27388052 TI - Retinal Ganglion Cell Layer Thinning Within One Month of Presentation for Non Arteritic Anterior Ischemic Optic Neuropathy. AB - PURPOSE: Optical coherence tomography reveals retinal ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thinning in chronic optic nerve injury. With acute optic nerve injury, as in acute nonarteritic anterior ischemic optic neuropathy (NAION), swelling obscures early demonstration of RNFL thinning, which might be used to evaluate therapies. We hypothesized that measurement of GCL plus inner plexiform layer (IPL) thickness and trajectory of thinning would show it is an earlier and more accurate biomarker of early permanent neuronal injury. METHODS: We prospectively studied 29 acute NAION eyes with standard automated perimetry and spectral domain (SD) optical coherence tomography for 6 months. We used a three-dimensional layer segmentation (method 1) and a commercial proprietary (method 2), to compute the combined thickness of macular GCL+IPL and method 2 to compute peripapillary RNFL thickness. RESULTS: At presentation, the mean GCL+IPL thickness (78.7 MUm +/- 8.9) for NAION eyes, did not differ from unaffected fellow eyes (83 MUm +/- 6.4), using method 1 while method 2 (66.8 MUm +/- 18.7) failed in 34% of NAION eyes. At 1 to 2 months, 12% had RNFL loss compared to baseline, while 68% of NAION eyes had GCL+IPL thinning. The ganglion cell layer plus inner plexiform layer reduction was greatest at 1 to 2 months (19.6 MUm +/- 12.6) and was minimally worse after month 3. Ganglion cell layer plus inner plexiform layer thinning showed moderate to strong significant correlation with the visual acuity and mean deviation at each exam time. The retinal nerve fiber layer was not thinned until month 3. CONCLUSIONS: Ganglion cell layer plus inner plexiform layer is acutely unaffected and provides a reliable measure of retinal neuronal structure using three-dimensional segmentation. Thinning develops within 1 to 2 months of onset, which is prior to RNFL swelling resolution. This suggests GCL+IPL measurement is better than the RNFL thickness to use as biomarker of early structural loss in NAION. PMID- 27388053 TI - Dibenzo-alpha-pyrones from the endophytic fungus Alternaria sp. Samif01: isolation, structure elucidation, and their antibacterial and antioxidant activities. AB - The EtOAc extract of the liquid fermentation of Alternaria sp. Samif01, an endophytic fungus obtained from Salvia miltiorrhiza Bunge, showed antibacterial activity against several tested bacterial pathogens. Fractionation of this extract led to the isolation of seven dibenzo-alpha-pyrones (1-7), including one new compound, 2-acetoxy-2-epi-altenuene (1) and one new natural product, 3-epi dihydroaltenuene A (2). The structures of the new metabolites were elucidated by comprehensive analysis of the spectroscopic data including (1D, 2D) NMR and HRESIMS, while the absolute configuration of 1 was determined by TDDFT-ECD computation. Altenuisol (5), 4-hydroxyalternariol-9-methyl ether (6), and alternariol (7) showed inhibitory activities against the tested bacteria with minimum inhibitory concentration values in the range of 86.7-364.7 MUM. A preliminary structure-antibacterial activity relationship was discussed. In addition, compounds 2, 5 and 6 displayed promising antioxidant effects using DPPH and hydroxyl radical assays. The cytotoxicity of the isolated compounds was evaluated as well. PMID- 27388054 TI - Vital Signs: Motor Vehicle Injury Prevention - United States and 19 Comparison Countries. AB - BACKGROUND: Each year >32,000 deaths and 2 million nonfatal injuries occur on U.S. roads. METHODS: CDC analyzed 2000 and 2013 data compiled by the World Health Organization and the Organisation for Economic Co-operation and Development (OECD) to determine the number and rate of motor vehicle crash deaths in the United States and 19 other high-income OECD countries and analyzed estimated seat belt use and the percentage of deaths that involved alcohol-impaired driving or speeding, by country. RESULTS: In 2013, the United States motor vehicle crash death rate of 10.3 per 100,000 population had decreased 31% from the rate in 2000; among the 19 comparison countries, the rate had declined an average of 56% during this time. Among all 20 countries, the United States had the highest rate of crash deaths per 100,000 population (10.3); the highest rate of crash deaths per 10,000 registered vehicles (1.24), and the fifth highest rate of motor vehicle crash deaths per 100 million vehicle miles traveled (1.10). Among countries for which information on national seat belt use was available, the United States ranked 18th out of 20 for front seat use, and 13th out of 18 for rear seat use. Among 19 countries, the United States reported the second highest percentage of motor vehicle crash deaths involving alcohol-impaired driving (31%), and among 15, had the eighth highest percentage of crash deaths that involved speeding (29%). CONCLUSIONS AND COMMENTS: Motor vehicle injuries are predictable and preventable. Lower death rates in other high-income countries, as well as a high prevalence of risk factors in the United States, suggest that the United States can make more progress in reducing crash deaths. With a projected increase in U.S. crash deaths in 2015, the time is right to reassess U.S. progress and set new goals. By implementing effective strategies, including those that increase seat belt use and reduce alcohol-impaired driving and speeding, the United States can prevent thousands of motor vehicle crash-related injuries and deaths and hundreds of millions of dollars in direct medical costs every year. PMID- 27388055 TI - Do Automated Peritoneal Dialysis and Continuous Ambulatory Peritoneal Dialysis Have the Same Clinical Outcomes? A Ten-year Cohort Study in Taiwan. AB - This paper reports a comprehensive comparison for mortality and technique failure rates between automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) in Taiwan. A propensity-score matched cohort study was conducted by retrieving APD and CAPD patients identified from the Taiwan National Health Insurance Research Database between 2001 and 2010. The main outcomes were the 5-year mortality and technique failure rates. Further analyses were then carried out based upon the first (2001-2004), second (2005-2007), and third (2008 2010) sub-periods. Similar baseline characteristics were identified for APD (n = 2,287) and CAPD (n = 2,287) patients. The proportion on APD therapy increased rapidly in the second sub-period. As compared to CAPD patients of this sub period, APD patients had a significantly higher risk of mortality (HR, 1.37; 95% CI 1.09-1.72; p < 0.01) and technique failure (HR, 1.43; 95% CI, 1.10-1.86; p < 0.01), particularly in the first year after peritoneal dialysis commencement. However, APD patients had similar mortality and technique failure rates to those of CAPD patients throughout the full sample period and the first and third sub periods. These findings do not suggest the presence of a clear advantage of CAPD over APD. Differences observed between these two modalities might be attributed to specials circumstances of sub-periods. PMID- 27388056 TI - Two Alkaloids from Bulbs of Lycoris sanguinea MAXIM. Suppress PEPCK Expression by Inhibiting the Phosphorylation of CREB. AB - In the fasting state, gluconeogenesis is upregulated by glucagon. Glucagon stimulates cyclic adenosine monophosphate production, which induces the expression of key enzymes for gluconeogenesis, such as cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), which are involved in gluconeogenesis through the protein kinase A/cAMP response element-binding protein (CREB) pathway. Using a luciferase reporter gene assay, a methanol extract of the bulbs of Lycoris sanguinea MAXIM. var. kiushiana Makino was found to suppress cAMP-enhanced PEPCK-C promoter activity. In addition, two alkaloids, lycoricidine and lycoricidinol, in the extract were identified as active constituents. In forskolin-stimulated human hepatoma cells, these alkaloids suppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated CREB and PEPCK mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress PEPCK-C expression by inhibiting the phosphorylation of CREB and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388057 TI - Surgical site infection prevention: a global priority. PMID- 27388058 TI - What every schoolboy knows. PMID- 27388059 TI - Prophylaxis guidelines: Plea to NICE. PMID- 27388060 TI - Oral health: The destructive effects of khat. PMID- 27388061 TI - Special care dentistry: Collaborative care. PMID- 27388062 TI - Dental radiography: Embarrassing foreign objects. PMID- 27388063 TI - Branches and sections: Here's to the future... PMID- 27388065 TI - Continued decline in dental academics. PMID- 27388064 TI - Anaesthesia: Pause for palsy. PMID- 27388073 TI - How to get published - autumn workshop. PMID- 27388075 TI - Bad teeth damage career prospects. PMID- 27388076 TI - Marcus Woof: 'Our goal is to have a dental student rep for GLADD at every dental school'. PMID- 27388077 TI - Emerging infections - implications for dental care. AB - Over the last 20 years the majority of emerging infections which have spread rapidly across the globe have been respiratory infections that are spread via droplets, a trend which is likely to continue. Aerosol spray generation in the dental surgery has the potential to spread such infections to staff or other patients. Although the diseases may differ, some common approaches can reduce the risk of transmission. Dental professionals should be aware of areas affected by emerging infections, the incubation period and the recent travel history of patients. Elective dental care for those returning from areas affected by emerging infections should be delayed until the incubation period for the infection is over. PMID- 27388079 TI - Biofilms: What does subgingival plaque look like? AB - The ultrastructure of subgingival dental plaque, revealed by high-resolution field emission scanning electron microscopy. PMID- 27388078 TI - Preventing evidence leaks. AB - How do we create, and improve, the evidence base? PMID- 27388080 TI - Pressure to prescribe antimicrobials. AB - Antimicrobial prescribing by dentists in Wales, UK: findings of the first cycle of a clinical audit. PMID- 27388081 TI - Sweet tooth: What pocket money is buying today. AB - The availability of novelty sweets within high school localities. PMID- 27388082 TI - Oral medicine: Factors associated with geographic tongue and fissured tongue. AB - Despite this study being of cross-sectional design, these investigators concur with others in suggesting that some subjects with geographic tongue go on to develop fissured tongue. PMID- 27388083 TI - Showjumping: Dental trauma in showjumping - a trinational study between Switzerland, France and Germany. AB - Most dental injuries, in contrast to injuries elsewhere on the body, occur when 'mucking out'. PMID- 27388084 TI - Avoiding a 'soggy bottom': Depth of cure of contemporary bulk-fill resin-based composites. AB - A depth of cure of 4 mm was not achieved in any of the bulk-fill resin composites. PMID- 27388085 TI - Counterfeit dental equipment: Counterfeit and non-compliant dental devices: the dangers and how to mitigate them. AB - Caveat emptor ('Let the buyer beware'). PMID- 27388086 TI - Management of orthodontic emergencies in primary care - self-reported confidence of general dental practitioners. AB - Objective To determine general dental practitioners' (GDPs) confidence in managing orthodontic emergencies.Design Cross-sectional study.Setting Primary dental care.Subjects and methods An online survey was distributed to dentists practicing in Wales. The survey collected basic demographic information and included descriptions of ten common orthodontic emergency scenarios.Main outcome measure Respondents' self-reported confidence in managing the orthodontic emergency scenarios on a 5-point Likert scale. Differences between the Likert responses and the demographic variables were investigated using chi-squared tests.Results The median number of orthodontic emergencies encountered by respondents over the previous six months was 1. Overall, the self-reported confidence of respondents was high with 7 of the 10 scenarios presented scoring a median of 4 indicating that GDPs were 'confident' in their management. Statistical analysis revealed that GDPs who saw more orthodontic emergencies in the previous six months were more confident when managing the presented scenarios. Other variables such as age, gender, geographic location of practice and number of years practising dentistry were not associated with self-reported confidence.Conclusions Despite GDPs encountering very few orthodontic emergencies in primary care, they appear to be confident in dealing with commonly arising orthodontic emergency situations. PMID- 27388087 TI - Antimicrobial prescribing by dentists in Wales, UK: findings of the first cycle of a clinical audit. AB - Objective To describe the findings of the first cycle of a clinical audit of antimicrobial use by general dental practitioners (GDPs).Setting General dental practices in Wales, UK.Subjects and methods Between April 2012 and March 2015, 279 GDPs completed the audit. Anonymous information about patients prescribed antimicrobials was recorded. Clinical information about the presentation and management of patients was compared to clinical guidelines published by the Scottish Dental Clinical Effectiveness Programme (SDCEP).Results During the data collection period, 5,782 antimicrobials were prescribed in clinical encounters with 5,460 patients. Of these 95.3% were antibiotic preparations, 2.7% were antifungal agents, and 0.6% were antivirals. Of all patients prescribed antibiotics, only 37.2% had signs of spreading infection or systemic involvement recorded, and 31.2% received no dental treatment. In total, 79.2% of antibiotic, 69.4% of antifungal, and 57.6% of antiviral preparations met audit standards for dose, frequency, and duration. GDPs identified that failure of previous local measures, patient unwillingness or inability to receive treatment, patient demand, time pressures, and patients' medical history may influence their prescribing behaviours.Conclusions The findings of the audit indicate a need for interventions to support GDPs so that they may make sustainable improvements to their antimicrobial prescribing practices. PMID- 27388088 TI - Looking after the mouth - Evaluation of a pilot for a new approach to training care home carers in Kent, Surrey and Sussex. AB - Objective This pilot study aimed to produce and evaluate training resources and training in oral health care, including oral hygiene, for carers in care homes in Surrey and Medway.Methods During two training days, for carers from these homes, short, interactive presentations were given on a range of topics relevant to oral health care and oral hygiene of older people, followed by practical training. Prior to any training all attendees completed a 39 question questionnaire to establish their baseline knowledge of oral health and hygiene. At the end of the training day they completed an evaluation form. Fourteen weeks later, they were visited at their place of work and completed the same questionnaire again. Differences in responses between baseline and after 14 weeks were statistically tested using the chi-squared test.Results Sixty-six carers attended the training sessions and 44 were followed up 14 weeks later. The results showed an improvement in carer knowledge at follow up. The majority of carers (36/44) spoke English as their first language. They had a mean age of 41 years, 37 were female and 7 male. They had worked as carers for a mean of 10.9 years (range 4 months-34 years). Over 90% stated that the training day fully met or exceeded their requirements and expectations.Conclusions The results indicated improvements in carer knowledge. However, the carers were atypical of carers in general, as they were self-selected and well-motivated. Nevertheless the content of the training day and the questionnaire should inform future work in this area. PMID- 27388102 TI - The influence of the surface composition of mixed monolayer films on the evaporation coefficient of water. AB - We explore the dependence of the evaporation coefficient of water from aqueous droplets on the composition of a surface film, considering in particular the influence of monolayer mixed component films on the evaporative mass flux. Measurements with binary component films formed from long chain alcohols, specifically tridecanol (C13H27OH) and pentadecanol (C15H31OH), and tetradecanol (C14H29OH) and hexadecanol (C16H33OH), show that the evaporation coefficient is dependent on the mole fractions of the two components forming the monolayer film. Immediately at the point of film formation and commensurate reduction in droplet evaporation rate, the evaporation coefficient is equal to a mole fraction weighted average of the evaporation coefficients through the equivalent single component films. As a droplet continues to diminish in surface area with continued loss of water, the more-soluble, shorter alkyl chain component preferentially partitions into the droplet bulk with the evaporation coefficient tending towards that through a single component film formed simply from the less soluble, longer chain alcohol. We also show that the addition of a long chain alcohol to an aqueous-sucrose droplet can facilitate control over the degree of dehydration achieved during evaporation. After undergoing rapid gas-phase diffusion limited water evaporation, binary aqueous-sucrose droplets show a continued slow evaporative flux that is limited by slow diffusional mass transport within the particle bulk due to the rapidly increasing particle viscosity and strong concentration gradients that are established. The addition of a long chain alcohol to the droplet is shown to slow the initial rate of water loss, leading to a droplet composition that remains more homogeneous for a longer period of time. When the sucrose concentration has achieved a sufficiently high value, and the diffusion constant of water has decreased accordingly so that bulk phase diffusion arrest occurs in the monolayer coated particle, the droplet is found to have lost a greater proportion of its initial water content. A greater degree of slowing in the evaporative flux can be achieved by increasing the chain length of the surface active alcohol, leading to a greater degree of dehydration. PMID- 27388089 TI - An algorithm of dental/dentofacial-based options for managing patients with obstructive sleep apnoea referred to a dentist/dental specialist by a physician. AB - There are so many documents in the literature discoursing the aetiology, nature, diagnosis and treatment planning of obstructive sleep apnoea (OSA). Almost all of them mention that OSA has to be evaluated and treated through the multidisciplinary teamwork of physicians and dentists. Due to a lack in the literature, this article focuses on dentists' and dental specialists' role in the treatment algorithm of OSA. PMID- 27388103 TI - Risk factors for temporary work disability. AB - INTRODUCTION: The relationship among labor difficulties and psychiatric disorders is important and bidirectional. However, current information about the influence of psychiatric disorders in temporary work disability in Spain is inconclusive. For this reason, we aimed to describe the prevalence of the conclusions of psychiatric expert’s reports including maintain o revoke the temporary disability (TD). We also aimed to compare sociodemographic, clinical and therapeutic variables according with the decision of maintain or revoke this condition. METHODOLOGY: A descriptive study was conducted in psychiatric patients that were examined by psychiatric experts during one year. At the examination time, the patients had a sick leave mean of 5 months. The psychiatric experts assessed their ability to work according to the interference of the psychiatric symptoms. RESULTS: A total of 380 patients were included (66.8% women, 42+/-10.9 years), 87.9% had a result of revoke the temporary work disability. No sociodemographic or therapeutic factors were associated with the continuity of sick leave. The most common diagnosis of patients who obtained a revoked temporary work disability was adjustment disorder (66.2% vs 13%, p=0.001) and patients who maintained the temporary work disability was major depressive disorder (45.7% vs 3.9%, p=0.001). CONCLUSIONS: After a psychiatric expert’s examination the most of the results suggest to revoke the temporary work disability. Major depressive disorder is the most commonly diagnostic associated to continue sick leave. PMID- 27388104 TI - Antipsychotic response in delusional disorder and schizophrenia: a prospective cohort study. AB - INTRODUCTION: Scientific evidence focused on the treatment response in delusional disorder (DD) patients is scarce, and the findings are controversial. Our goal was to compare the antipsychotic response at the 12-week followup between patients diagnosed with DD and patients diagnosed with schizophrenia and to identify potential response dimensions. METHODS: A prospective, observational, cohort study with 12-week follow-up was conducted with DD and schizophrenia patients matched for sex, age and cumulative years of disease. The following scales were assessed: Positive and Negative Syndrome Scale (PANSS; 5-factors), Personal and Social Performance Scale (PSP), Clinical Global Impression Scale (CGI), and Columbia-Suicide Severity Rating Scale (C-SSRS). Treatment response was defined as a ≥30% reduction in the total PANSS score. Linear and logistic regression models were used to investigate the potential predictive value of psychopathological variables for the antipsychotic response. RESULTS: Response percentages in DD and schizophrenia were 61.5% and 69.2%, respectively. The duration of untreated psychosis, antipsychotic dosage, and diagnosis did not predict antipsychotic response. In the whole sample, improvement in positive symptoms was significantly associated with the clinical global improvement (p=0.006), explaining almost 20% of the variance in the model. Within the DD group, improvement in cognitive symptoms explained 30% of the variance in clinical global improvement. CONCLUSIONS: Both response percentages and required antipsychotic doses were similar between DD and schizophrenia. Changes in positive symptoms were associated with clinical global improvement in the entire sample, and improvement in cognitive symptoms was correlated with global improvement exclusively in DD. PMID- 27388105 TI - Reduction in serum concentration of valproic acid secondary to the intake of ibuprofen as an example of valproic acid auto-induction metabolism. AB - INTRODUCTION: In 1998, an unexplained drug-drug interaction between valproic acid (VPA) and ibuprofen was reported. VPA has been considered a moderate inhibitor of several metabolic enzymes, but recently its inductive properties have been described, including the possibility of auto-induction. Ibuprofen can displace VPA from the plasmatic protein, increasing its serum free concentration, and subsequently its pharmacological actions, including auto-induction. The objective of this article is to describe a similar case and to contribute to the clarification of the underlying pharmacokinetic mechanisms. METHODS: A 29-year old Spanish Caucasian male with schizophrenia was followed with steady-state trough serum concentrations of VPA and clozapine for 5 years, including 3 ibuprofen trials. The main outcome variable was the concentration-to-dose (C/D) ratio, a measure of the ability to eliminate a drug. Independent sample Mann Whitney U tests were performed to compare C/D ratios. RESULTS: Five VPA C/D ratios, contaminated by VPA auto-induction occurring during or shortly after the two latter ibuprofen trials, were significantly lower (p<0.001) than the other 34 VPA C/D ratios of VPA not contaminated by auto-induction. During the highest ibuprofen dose in the third trial, the patient had two very low clozapine C/D ratios, which were significantly lower than the other 26 clozapine C/D ratios (p=0.021). CONCLUSIONS: Reduction in total VPA concentrations could be explained by ibuprofen displacing VPA from the plasma proteins, increasing the serum free VPA. This may induce the metabolism of VPA (and clozapine) and subsequently decrease their serum total concentrations. PMID- 27388106 TI - Impulsive clinical profile of Borderline Personality Disorder with comorbid Substance Use Disorder. AB - INTRODUCTION: Borderline Personality Disorder (BPD) is one of the Personality Disorder most frequently associated with Substance Use Disorder (SUD). According to different models, the Behavioral dysregulation-BPD subgroup has a higher prevalence of SUD and certain impulsivity behaviors than the other two subgroups. METHODS: Out of 156 BPD patients, 47 were in the Behavioral dysregulation-BPD subgroup, 55 in Affective dysregulation, and 54 in Disturbed relatedness. All patients completed the SCID-II for DSM-IV Axis II Disorders, SCID-I for DSM-IV Axis I Disorders, Barratt Impulsiveness Scale (BIS-11) and Revised Diagnostic Interview for Borderlines (DIB-R). RESULTS: In the comparison of the BPD subgroups, Behavioral dysregulation showed significantly more prevalence of SUD (alcohol and cocaine), and tendency for anxiolytics, higher impulsivity (DIB-R, but none in BIS-11), and higher number of suicide attempts and psychiatric admissions, although these was not significant in comparison with the other subgroups. CONCLUSIONS: This should be especially useful in the discrimination of BPD patients for different therapeutic approaches and prognoses. PMID- 27388107 TI - Key clinical data in the differential diagnosis between onset of Bipolar Disorder and Borderline Personality Disorder. PMID- 27388108 TI - Mindfulness terminology in the Spanish scientific literature: used terms and definitions. PMID- 27388109 TI - Polypoidal choroidal vasculopathy. PMID- 27388110 TI - Multimodal imaging in neovascular Age-Related Macular Degeneration. PMID- 27388111 TI - Conjunctival lymphoma in right eye: Case report. AB - CASE REPORT: A 43-year-old woman presented with a salmon-coloured patch of 0.7mm diameter in the right eye that extended into the lower fornix in the bulbar and tarsal conjunctiva, with irregular edges, and highly vascularised. Incisional biopsy was performed, showing it to be a low-grade conjunctival non-Hodgkin B cell lymphoma (or a mucosa associated lymphoid tissue [MALT] lymphoma). DISCUSSION: The lesion remained stable for 24 months of follow-up, when a relapse of the condition occurred, producing an enlargement of the initial lesion. The definitive diagnosis is made by biopsy of the affected tissue and histopathologic study. PMID- 27388112 TI - Impact of the bacteriology of diabetic foot ulcers in limb loss. AB - Infections in feet of patients with diabetes mellitus is common, complex and costly. The aim of this study to investigate the isolated microorganisms in infected diabetic foot ulcers, and the impact of these infectious agents in limb loss in a tertiary medical center in Mexico City. We conducted a retrospective review in diabetic patients with infected foot ulcers from 1997 to 2014. Diabetic foot was defined according to the World Health Organization (WHO), the bacteriology of wound cultures and the impact of microorganisms in limb loss (major amputation) was studied. Patient's demographics, comorbidities, wound characteristics, and other factors associated in clinical outcomes were determined. A total of 165 subjects with soft tissue infections and/or osteomyelitis and positive cultures were included. One hundred and five (64%) were male, with a mean age of 60 year old +/- 15. One hundred fifty-nine (96%) had Type 2 diabetes mellitus, 68 (41%) history of peripheral arterial disease (PAD) and 97 (59%) patients had osteomyelitis. In 89 patients (54%), cultures were polymicrobial and one single organism was isolated in 76 cultures (46%). During the follow up, 96 (58%) patients preserved their limbs and 69 (42%) required major amputation (above or below knee). Sixty percent of patients that suffered from limb loss had polymicrobial culture (p = 0.13). Growth of Escherichia coli and Enterococcus faecium (p = 0.03) and E. coli and Morganella morgagnii (p = 0.03) was associated to limb loss. Among monomicrobial cultures, infections associated with Proteous mirabilis had higher rate of progression to limb loss (p = 0.03). PAD was associated to limb loss (p = 0.001). Management of diabetic foot requires a multimodality approach. In this study, in patients that received appropriate antibiotic therapy and optimal surgical management, we observed that history of PAD, polymicrobial and isolated P. mirabilis infections were variables associated with higher rate of limb loss. PMID- 27388113 TI - A planar triangular Dy3 + Dy3 single-molecule magnet with a toroidal magnetic moment. AB - A unique Dy6 complex with a planar Dy3 + Dy3 structure was assembled by delicately modifying the axial ligands. Single-molecule magnet behavior and meanwhile a toroidal magnetic moment in the ground state have been observed. PMID- 27388114 TI - Amelioration of scopolamine-induced amnesia by phosphatidylserine and curcumin in the day-old chick. AB - In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease. PMID- 27388115 TI - Phonons, Localization, and Thermal Conductivity of Diamond Nanothreads and Amorphous Graphene. AB - Recently, the domains of low-dimensional (low-D) materials and disordered materials have been brought together by the demonstration of several new low-D, disordered systems. The thermal transport properties of these systems are not well-understood. Using amorphous graphene and glassy diamond nanothreads as prototype systems, we establish how structural disorder affects vibrational energy transport in low-dimensional, but disordered, materials. Modal localization analysis, molecular dynamics simulations, and a generalized model together demonstrate that the thermal transport properties of these materials exhibit both similarities and differences from disordered 3D materials. In analogy with 3D, the low-D disordered systems exhibit both propagating and diffusive vibrational modes. In contrast to 3D, however, the diffuson contribution to thermal transport in these low-D systems is shown to be negligible, which may be a result of inherent differences in the nature of random walks in lower dimensions. Despite the lack of diffusons, the suppression of thermal conductivity due to disorder in low-D systems is shown to be mild or comparable to 3D. The mild suppression originates from the presence of low frequency vibrational modes that maintain a well-defined polarization and help preserve the thermal conductivity in the presence of disorder. PMID- 27388116 TI - Localization of Peripheral Pulmonary Lesions Using a Method of Computed Tomography-Anatomic Correlation and Radial Probe Endobronchial Ultrasound Confirmation. AB - RATIONALE: Peripheral pulmonary lesions requiring a diagnosis continue to present challenges to clinicians. One significant barrier is the inability to reliably locate peripheral lesions by bronchoscopic approaches. Multiplanar computed tomographic (CT) scan reconstruction is available to most physicians and provides axial, coronal, and sagittal images that may be used to estimate target lesion location and guide bronchoscopists during procedures. OBJECTIVES: This study was performed to evaluate a systematic method of CT-anatomic correlation based on multiplanar reconstruction CT scanning with monoplanar fluoroscopy during bronchoscopy to locate peripheral pulmonary lesions and confirm lesion location, using radial probe endobronchial ultrasound. METHODS: A retrospective review of peripheral bronchoscopy cases in which radial probe endobronchial ultrasound for peripheral lesions was performed at a tertiary care, university hospital. All cases involved a systematic approach of reviewing axial, coronal, and sagittal CT reconstructions, coupled with monoplanar fluoroscopy during procedures to assist with locating peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Using the method of CT-anatomic correlation, 332 of 348 (95.4%) of all lesions were successfully localized and confirmed, using radial probe endobronchial ultrasound. Lesions 1-2 cm in size accounted for 45% of all lesions, and the ability to locate lesions was not significantly different based on lesion size. Mean time to lesion localization was 6.8 minutes. Larger lesions and lesions demonstrating an air bronchus sign on CT scan were located in less time. The overall diagnostic yield was 58.9%. CONCLUSIONS: A systematic approach applying CT-anatomic correlation with multiplanar CT scan reconstruction and monoplanar fluoroscopy during procedures can result in an efficient, and successful process for locating peripheral pulmonary lesions. PMID- 27388117 TI - Li(+) Local Structure in Li-Tetraglyme Solvate Ionic Liquid Revealed by Neutron Total Scattering Experiments with the (6/7)Li Isotopic Substitution Technique. AB - Equimolar mixtures of lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) and tetraglyme (G4: CH3O-(CH2CH2O)4-CH3) yield the solvate (or chelate) ionic liquid [Li(G4)][TFSA], which is a homogeneous transparent solution at room temperature. Solvate ionic liquids (SILs) are currently attracting increasing research interest, especially as new electrolytes for Li-sulfur batteries. Here, we performed neutron total scattering experiments with (6/7)Li isotopic substitution to reveal the Li(+) solvation/local structure in [Li(G4)][TFSA] SILs. The experimental interference function and radial distribution function around Li(+) agree well with predictions from ab initio calculations and MD simulations. The model solvation/local structure was optimized with nonlinear least-squares analysis to yield structural parameters. The refined Li(+) solvation/local structure in the [Li(G4)][TFSA] SIL shows that lithium cations are not coordinated to all five oxygen atoms of the G4 molecule (deficient five coordination) but only to four of them (actual four-coordination). The solvate cation is thus considerably distorted, which can be ascribed to the limited phase space of the ethylene oxide chain and competition for coordination sites from the TFSA anion. PMID- 27388118 TI - Balancing quality with quantity: The role of palliative care in managing decompensated cirrhosis. PMID- 27388119 TI - Molecular dynamics at the receptor level of immunodominant myelin oligodendrocyte glycoprotein 35-55 epitope implicated in multiple sclerosis. AB - Multiple Sclerosis (MS) is a common autoimmune disease whereby myelin is destroyed by the immune system. The disease is triggered by the stimulation of encephalitogenic T-cells via the formation of a trimolecular complex between the Human Leukocyte Antigen (HLA), an immunodominant epitope of myelin proteins and T cell Receptor (TCR). Myelin Oligodendrocyte Glycoprotein (MOG) is located on the external surface of myelin and has been implicated in MS induction. The immunodominant 35-55 epitope of MOG is widely used for in vivo biological evaluation and immunological studies that are related with chronic Experimental Autoimmune Encephalomyelitis (EAE, animal model of MS), inflammatory diseases and MS. In this report, Molecular Dynamics (MD) simulations were used to explore the interactions of MOG35-55 at the receptor level. A detailed mapping of the developed interactions during the creation of the trimolecular complex is reported. This is the first attempt to gain an understanding of the molecular recognition of the MOG35-55 epitope by the HLA and TCR receptors. During the formation of the trimolecular complex, the residues Arg(41) and Arg(46) of MOG35 55 have been confirmed to serve as TCR anchors while Tyr(40) interacts with HLA. The present structural findings indicate that the Arg at positions 41 and 46 is a key residue for the stimulation of the encephalitogenic T-cells. PMID- 27388120 TI - Theoretical and experimental investigation on the capture of H2S in a series of ionic liquids. AB - H2S absorptions in ionic liquids (ILs), including tetramethyl guanidinelactate (TMGL), 4-bis(2-hydroxypropyl)-1,1,3,3-tetramethyl guanidinium tetrafluoroborate ([TMGHPO2][BF4]) and 1-butyl-3-methylimidazolium cation ([BMIM](+)) with the anions chloride ([Cl](-)), tetrafluoroborate ([BF4](-)), hexafluorophosphate ([PF6](-)), triflate ([TfO](-)), bis-(trifluoromethyl) sulfonylimide ([Tf2N](-)), were studied in experiment and computational methods. [TMGHPO2][BF4] showed the best H2S absorption capacity among the seven ILs. Density functional theory (DFT) calculations were applied to reveal the absorption mechanisms. Interaction energy results were consistent with absorptivities (molar ratio of H2S in IL) measured in experiment. As the best candidate absorbent, [TMGHPO2][BF4] was chosen as an example to characterize the hydrogen bonds and orbital interactions between H2S and [TMGHPO2][BF4] in atoms in molecules (AIM) and natural bond orbital (NBO) methods, respectively. IR spectrums obtained in both experimental and computational method were used to characterize the features of absorption process. The results indicated that H2S was physically absorbed by ILs, in which hydrogen bond was the driving force. PMID- 27388121 TI - Tuning the push-pull configuration for efficient second-order nonlinear optical properties in some chalcone derivatives. AB - Using the density functional theory methods, we effectively tune the second-order nonlinear optical (NLO) properties in some chalcone derivatives. Various unique push-pull configurations are used to efficiently enhance the intramolecular charge transfer process over the designed derivatives, which result in significantly larger amplitudes of the first hyperpolarizability as compared to their parent molecule. The ground state molecular geometries have been optimized using B3LYP/6-311G** level of theory. A variety of methods including B3LYP, CAM B3LYP, PBE0, M06, BHandHLYP and MP2 are tested with 6-311G** basis set to calculate the first hyperpolarizability of parent system 1. The results of M06 are found closer to highly correlated MP2 method, which has been selected to calculate static and frequency dependent first hyperpolarizability amplitudes of all selected systems. At M06/6-311G** level of theory, the permanent electronic dipole moment (MUtot), polarizability (alpha0) and static first hyperpolarizability (betatot) amplitudes for parent system 1 are found to be 5.139 Debye, 274a. u. and 24.22*10(-30)esu, respectively. These amplitudes have been significantly enhanced in designed derivatives 2 and 3. More importantly, the (betatot) amplitudes of systems 2 and 3 mount to 75.78*10(-30) and 128.51*10( 30)esu, respectively, which are about 3 times and 5 times larger than that of their parent system 1. Additionally, we have extended the structure-NLO property relationship to several newly synthesized chalcone derivatives. Interestingly, the amplitudes of dynamic frequency dependent hyperpolarizability MUbetaomega (SHG) are also significantly larger having values of 366.72*10(-48), 856.32*10( 48) and 1913.46*10(-48)esu for systems 1-3, respectively, at 1400nm of incident laser wavelength. The dispersion behavior over a wide range of change in wavelength has also been studied adopting a range of wavelength from 1907 to 544nm. Thus, the present work realizes the potential of designed derivatives as efficient NLO-phores for modern NLO applications. PMID- 27388122 TI - Mie Resonance-Modulated Spatial Distributions of Photogenerated Carriers in Poly(3-hexylthiophene-2,5-diyl)/Silicon Nanopillars. AB - Organic/silicon hybrid solar cells have great potential as low-cost, high efficiency photovoltaic devices. The superior light trapping capability, mediated by the optical resonances, of the organic/silicon hybrid nanostructure-based cells enhances their optical performance. In this work, we fabricated Si nanopillar (NP) arrays coated with organic semiconductor, poly(3-hexylthiophene 2,5-diyl), layers. Experimental and calculated optical properties of the samples showed that Mie-resonance strongly concentrated incoming light in the NPs. Spatial mapping of surface photovoltage, i.e., changes in the surface potential under illumination, using Kelvin probe force microscopy enabled us to visualize the local behavior of the photogenerated carriers in our samples. Under red light, surface photovoltage was much larger (63 meV) on the top surface of a NP than on a planar sample (13 meV), which demonstrated that the confined light in the NPs produced numerous carriers within the NPs. Since the silicon NPs provide pathways for efficient carrier transportation, high collection probability of the photogenerated carriers near the NPs can be expected. This suggests that the optical resonance in organic/silicon hybrid nanostructures benefits not only broad-band light trapping but also efficient carrier collection. PMID- 27388125 TI - Chlorine-doped reduced graphene oxide nanosheets as an efficient and stable electrode for supercapacitor in acidic medium. AB - We demonstrate the efficient doping of reduced graphene oxide (RGO) by Chlorine and its capacitive performance was calculated by cyclic voltammetry and charge discharge cycling in 1M H2SO4 solution. In this regard, we are prepared RGO nanosheets through a simple, eco-friendly and efficient electrochemical method, with selectively functionalized edges by chlorine which involves added the RGO to the halogen-containing acid solution and dispersed by ultrasonic. After synthesis, Cl-RGO is characterized using X-ray diffraction, Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy and tunneling electron microscopy. FTIR spectra show the chlorine containing functional groups. Energy-dispersive X-ray spectroscopy analysis confirmed the presence of doped chlorine in RGO. Raman spectroscopy shows a high density of defects in the RGO layer. Electrochemical characteristics of Cl-RGO are characterized by cyclic voltammetery, galvanostatic charge/discharge and electrochemical impedance spectroscopy. According to the galvanostatic charge/discharge analysis, Cl-RGO represents specific capacitance (Cs) of 178.4Fg(-1) at current density of 1Ag(-1), which is higher than that of RGO (100.5Fg(-1)) in H2SO4 solution. PMID- 27388123 TI - Moving forward with human papillomavirus immunotherapies. AB - Persistent human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and causes a significant number of vulvar, penile, anal and oropharyngeal cancers. The development of highly effective HPV therapeutic vaccines is a reasonable goal given the recent advances in basic and applied immunology. A number of vaccine strategies designed to induce systemic T cell responses have been tested in clinical trials against high grade cervical or vulvar high grade neoplasia and cancers, but with limited success. In line with the emerging trend to focus more on the epithelial context of HPV infection and premalignant disease, it might be advantageous to develop vaccination strategies that promote trafficking of HPV-specific T cells into lesions and overcome the local immunosuppressive environment. The development of more biologically relevant animal models would improve the preclinical evaluation of therapeutic vaccine candidates. Finally, persistent infection and low grade lesions may prove to be easier targets for therapeutic vaccines, and these vaccines would likely be commercially viable in high income countries and valuable components in screen and treat programs in low resource settings. PMID- 27388126 TI - Highly selective NH3 gas sensor based on Au loaded ZnO nanostructures prepared using microwave-assisted method. AB - ZnO nanorods synthesized using microwave-assisted approach were functionalized with gold (Au) nanoparticles. The Au coverage on the surface of the functionalized ZnO was controlled by adjusting the concentration of the Au precursor. According to X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) results, it was confirmed that Au form nanoparticles loaded on the surface of ZnO. The small Au loading level of 0.5wt% showed the highest response of 1600-100ppm of NH3 gas at room temperature (RT) whereas further increase of Au loading level resulted in poor detection of NH3. All Au loaded ZnO (Au/ZnO) based sensors exhibited very short recovery and response times compared to unloaded ZnO sensing materials. The responses of ZnO and Au/ZnO based sensors (0.5-2.5wt%) to other flammable gases, including H2, CO and CH4, were considerably less, demonstrating that Au/ZnO based sensors were highly selective to NH3 gas at room temperature. Spill over mechanism which is the main reason for the observed enhanced NH3 response with 0.5 Au loading level is explained in detail. PMID- 27388124 TI - Peroxiredoxin 1 interacts with and blocks the redox factor APE1 from activating interleukin-8 expression. AB - APE1 is an essential DNA repair protein that also possesses the ability to regulate transcription. It has a unique cysteine residue C65, which maintains the reduce state of several transcriptional activators such as NF-kappaB. How APE1 is being recruited to execute the various biological functions remains unknown. Herein, we show that APE1 interacts with a novel partner PRDX1, a peroxidase that can also prevent oxidative damage to proteins by serving as a chaperone. PRDX1 knockdown did not interfere with APE1 expression level or its DNA repair activities. However, PRDX1 knockdown greatly facilitates APE1 detection within the nucleus by indirect immunofluorescence analysis, even though APE1 level was unchanged. The loss of APE1 interaction with PRDX1 promotes APE1 redox function to activate binding of the transcription factor NF-kappaB onto the promoter of a target gene, the proinflammatory chemokine IL-8 involved in cancer invasion and metastasis, resulting in its upregulation. Depletion of APE1 blocked the upregulation of IL-8 in the PRDX1 knockdown cells. Our findings suggest that the interaction of PRDX1 with APE1 represents a novel anti-inflammatory function of PRDX1, whereby the association safeguards APE1 from reducing transcription factors and activating superfluous gene expression, which otherwise could trigger cancer invasion and metastasis. PMID- 27388127 TI - Tuning the architectural integrity of high-performance magneto-fluorescent core shell nanoassemblies in cancer cells. AB - High-density nanoarchitectures, endowed with simultaneous fluorescence and contrast properties for MRI and TEM imaging, have been obtained using a simple self-assembling strategy based on supramolecular interactions between non-doped fluorescent organic nanoparticles (FON) and superparamagnetic nanoparticles. In this way, a high-payload core-shell structure FON@mag has been obtained, protecting the hydrophobic fluorophores from the surroundings as well as from emission quenching by the shell of magnetic nanoparticles. Compared to isolated nanoparticles, maghemite nanoparticles self-assembled as an external shell create large inhomogeneous magnetic field, which causes enhanced transverse relaxivity and exacerbated MRI contrast. The magnetic load of the resulting nanoassemblies is evaluated using magnetic sedimentation and more originally electrospray mass spectrometry. The role of the stabilizing agents (citrate versus polyacrylate anions) revealed to be crucial regarding the cohesion of the resulting high performance magneto-fluorescent nanoassemblies, which questions their use after cell internalization as nanocarriers or imaging agents for reliable correlative light and electron microcopy. PMID- 27388128 TI - Scalable synthesis of mesoporous titania microspheres via spray-drying method. AB - Mesoporous TiO2 has several potential applications due to its unique electronic and optical properties, although its structures and morphologies are typically difficult to tune because of its uncontrollable and fast sol-gel reaction. In this study we have coupled the template-directed-sol-gel-chemistry with the low cost, scalable, and environmentally benign aerosol (spray-drying) one-pot preparation technique for the fabrication of hierarchically mesoporous TiO2 microspheres and Fe3O4@mesoporous TiO2-x microspheres in a large scale. Parameters during the pre-hydrolysis and spray-drying treatment were varied to successfully control the bead diameter, morphology, monodispersity, surface area and pore size for improving their effectiveness for better application. Unlike to the previous aerosol synthetic approaches, where mainly quite a high temperature gradient with the strict control of spray-drying precursor concentration is implied, our strategy is lying on comparatively low drying temperature with an additional post-ultrasonication (further hydrolysis and condensation) route of the pre-calcined TiO2 samples. As-synthesized mesoporous microspheres have a size distribution from 500nm to 5MUm, specific surface areas ranging from 150 to 162m(2)g(-1) and mean pore sizes of several nanometers (4-6nm). Further Fe3O4@mesoporous TiO2-x microspheres were observed to show remarkable selective phosphopeptide-enrichment activity which might have significant importance in disease diagnosis and other biomedical applications. PMID- 27388129 TI - Synthesis and characterization of tannin grafted polycaprolactone. AB - Tannin and biodegradable polyester have attracted increasing interest for biomedical applications. To improve their compatibility, a novel tannin grafted polycaprolactone (TA-g-PCL) has been synthesized via ring-opening polymerization reaction. The structure of the product is characterized with FTIR, (1)H NMR and GPC. GPC results show that the experimental molecular weight is far less than the theoretical due to complicated stereo structure and large steric hindrance of tannic molecule, but the polydispersity of the product is narrow. At 115.76:1 of molar ratio of CL to tannin, molecular weight of the product reaches the maximum. Thermodynamics properties and dissolubility of TA-g-PCL are closely related to its molecular weight. With PCL molecular chain grows, TA-g-PCL changes from amorphous form to crystalline structure, and its dissolubility in chloroform is also enhanced significantly. PMID- 27388130 TI - Breaking of double emulsions based on electrohydrodynamics principles. AB - This research focuses on the modeling of the liquid-liquid dispersed system, including particular insight on the electrocoalescence (EC) process that occurs during the breaking of double emulsions. The representative system, used in this work, was taken from the pilot plant for solvent extraction of uranium from wet phosphoric acid. The chosen framework required for elucidation of the EC process is based on the electrohydrodynamic (EHD) principles. During the model development it was necessary to consider several theoretical concepts for easier understanding and description of the related events. The first is the concept of entities, and corresponding classification of finely dispersed systems. The second concept is an introduction of almost forgotten basic electrodynamics element the memdiode or memristor as a current controlled device, and corresponding memristive systems. Hence, the conclusions that may be withdrawn from the presented results and findings could enable easier designing of the solutions for a breaking of double emulsions problems, that is, the entrainment problems that may arise in some pilot or industrial plants. Finally, the perspectives and the remaining challenges, considering the here discussed concepts and model based on the EHD principles, are mentioned. PMID- 27388131 TI - Sub-monolayer silver loss from large gold nanospheres detected by surface plasmon resonance in the sigmoidal region. AB - Nanosilver becomes labile upon entering the human body or the environment. This lability creates silver species with antimicrobial properties that make nanosilver attractive as active components in many consumer products, wound dressings, and agricultural applications. Because lability depends strongly on morphology, it is imperative to use a material with constant lability throughout kinetic studies so that accurate lability data can be acquired with efficient detection. Here 2.5nm thick silver was coated onto 90-nm diameter gold nanosphere cores and this surface silver layer was gradually removed by either chemical or X ray radiation etching. The most sensitive region of a sigmoidal surface plasmon resonance (SPR) response as a function of silver thickness was found for the first time between 0.9- and 1.6-nm thick silver, revealing a new nanosilver standard for lability studies. The SPR peak position detection sensitivity is 8nm (SPR peak shift)/nm (silver thickness change) within this steepest region of the plasmon response curve whereas outside, sensitivity drops to 1nm/nm. Since the centroid of SPR profiles can be discerned with 0.25nm precision, the 8-nm/nm sensitivity means it is possible to detect a 0.3-angstrom or sub-monolayer change in silver thickness. The SPR response simulated by discrete dipole approximation (DDA) was an identical sigmoidal function between 0 and 2nm of silver coating. These findings were supported by several other analytical measurements, which confirmed no silver recoating during these etching processes. PMID- 27388132 TI - Self-propulsion of a metallic superoleophobic micro-boat. AB - The self-propulsion of a heavy, superoleophobic, metallic micro-boat carrying a droplet of various aqueous alcohol solutions as a fuel tank is reported. The micro-boat is driven by the solutocapillary Marangoni flow. The jump in the surface tension owing to the condensation of alcohols on the water surface was established experimentally. Maximal velocities of the self-propulsion were registered as high as 0.05m/s. The maximal velocity of the center mass of the boat correlates with the maximal change in the surface tension, due to the condensation of alcohols. The mechanism of the self-locomotion is discussed. The phenomenological dynamic model describing the self-propulsion is reported. PMID- 27388133 TI - Vortex formation in coalescence of droplets with a reservoir using molecular dynamics simulations. AB - The flow patterns generated by the coalescence of aqueous ethanol droplets with a water reservoir are investigated using molecular dynamics simulations. The influence of surface tension gradient, which leads to the spreading of the droplet along the liquid-vapor interface of the reservoir, is studied by changing the ethanol concentration of the droplet. The internal circulation (vortex strength) of the droplet and the reservoir are analyzed separately. Simulation results reveal the formation of swirling flows within the droplet at early times when the radius of the coalescence neck due to the capillary forces increases rapidly with time. The vortex strength is found to be higher at lower concentrations of ethanol (higher liquid-vapor surface tension of the droplet), where the driving force for the contact line movement (capillary force) is stronger. The circulation diminishes by moving the center of mass of the droplet toward the reservoir. The lower surface tension of the droplet compared to the reservoir leads to surface tension gradient driven flow, which transports the droplet molecules along the liquid-vapor interface of the reservoir. Such a flow motion results in the generation of convective flows in the underlying water, which forms swirling flows within the reservoir. Therefore, the vortex strength of the reservoir is higher at higher ethanol concentrations of the droplet. The reservoir circulation decays to zero as soon as the ethanol concentration becomes homogeneous along the interface of the pool. The time evolution of circulation within the droplet and the reservoir are correlated with the center of mass motion of the droplet toward the surface, the time variation of the precursor film radius and the dynamic surface tension of the reservoir. PMID- 27388134 TI - Adsorption and rheological behavior of an amphiphilic protein at oil/water interfaces. AB - Hydrophobins are highly surface active proteins which self-assemble at hydrophilic-hydrophobic interfaces into amphipathic membranes. We investigate hydrophobin self-assembly at oil/water interfaces to deepen the understanding of protein behavior in order to improve our biomimetic synthesis. Therefore, we carried out pendant drop measurements of hydrophobin stabilized oil/water systems determining the time-dependent IFT and the dilatational rheology with additional adaptation to the Serrien protein model. We show that the class I hydrophobin H(*)Protein B adsorbs at an oil/water interface where it forms a densely-packed interfacial protein layer, which dissipates energy during droplet oscillation. Furthermore, the interfacial protein layer exhibits shear thinning behavior. PMID- 27388135 TI - The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier. AB - In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol. PMID- 27388136 TI - Hemilaminectomy for spinal meningioma: A case series of 20 patients with a focus on ventral- and ventrolateral lesions. AB - OBJECTIVE: To demonstrate the effectiveness and safety of hemilaminectomy in spinal-meningioma surgery, with special attention to ventral lesions. We also describe technical tips to enhance surgical-corridor width. PATIENTS AND METHODS: A total of 20 patients (14 female and 6 male) underwent hemilaminectomy for resection of a spinal meningioma between January 2005 and December 2015. Preoperative magnetic resonance imaging defined the tumor location (16 thoracic, 3 cervical, 1 lumbar) and the dural-attachment site (4 ventral, 11 ventrolateral, 3 lateral, 2 posterior). Pre- and postprocedural functional status was evaluated according to McCormick's classification. Intraoperative neurophysiological monitoring was employed in all patients. RESULTS: The unilateral approach allowed for complete resection (Simpson grade I-II resection) in 18 patients (90%), including tumors with a ventral dural attachment. In most patients (n=13), monosegmental hemilaminectomy was performed, a single patient required hemilaminectomy of 3 levels, while the remaining 6 patients underwent hemilaminectomy of 2 levels. No patients experienced either worsening of neurological status or procedure-related complications. All patients who had preoperative pain reported postoperative improvement. CONCLUSIONS: The goal of surgery for spinal tumors is to achieve gross tumor removal while minimizing morbidity. In our experience, hemilaminectomy is an effective surgical approach, even in patients with ventral- and ventrolateral spinal meningiomas. The procedure offers several advantages in terms of early patient mobilization and rehabilitation, management of postoperative pain, and preservation of spinal stability while achieving positive functional outcomes. PMID- 27388137 TI - Combined monitoring of intracranial pressure and bispectral index in patients with severe craniocerebral trauma post-operatively. AB - OBJECTIVE: To investigate the value of simultaneous bispectral index (BIS) and intracranial pressure (ICP) monitoring to evaluate postoperative consciousness and short-term prognosis in patients with severe traumatic brain injury. METHODS: We evaluated 30 brain trauma coma patients in the People's Hospital of Northern Jiangsu Province from January 2014 to December 2014 and evaluated Glasgow Coma Scale (GCS) scores at 8-h intervals for 3days after surgery. BIS and ICP values were recorded at the same time. Based on the GCS score, patients were divided into two groups: group A (GCS score 3-<=5) and group B (>5-<=8). Natural survival rates were analyzed statistically and compared between groups. RESULTS: Chi square testing revealed a significant difference in survival rates between the groups (P<0.05). Spearman's rank correlation analysis revealed that BIS value was positively correlated with coma degree post-operatively in patients with severe traumatic brain injury, and negatively correlated with ICP values (r=0.532, P<0.05; r=0.521, P<0.05, respectively). CONCLUSION: In patients with severe craniocerebral injury, higher severity, higher ICP, and lower BIS were associated with a worse prognosis. Combined monitoring of BIS and ICP is very useful when evaluating the coma degree and prognosis of patients with severe craniocerebral injury post-operatively. PMID- 27388138 TI - Where civics meets science: building science for the public good through Civic Science. AB - Public understanding of science and civic engagement on science issues that impact contemporary life matter more today than ever. From the Planned Parenthood controversy, to the Flint water crisis and the fluoridation debate, societal polarization about science issues has reached dramatic levels that present significant obstacles to public discussion and problem solving. This is happening, in part, because systems built to support science do not often reward open-minded thinking, inclusive dialogue, and moral responsibility regarding science issues. As a result, public faith in science continues to erode. This review explores how the field of Civic Science can impact public work on science issues by building new understanding of the practices, influences, and cultures of science. Civic Science is defined as a discipline that considers science practice and knowledge as resources for civic engagement, democratic action, and political change. This review considers how Civic Science informs the roles that key participants-scientists, public citizens and institutions of higher education play in our national science dialogue. Civic Science aspires to teach civic capacities, to inform the responsibilities of scientists engaged in public science issues and to inspire an open-minded, inclusive dialogue where all voices are heard and shared commitments are acknowledged. PMID- 27388139 TI - RE: Temporal Changes of Intra-Appendiceal Air at CT in the Diagnosis of Acute Appendicitis. PMID- 27388140 TI - A Description of Suicides in the Army National Guard During 2007-2014 and Associated Risk Factors. AB - Suicide, due to its increased occurrence in recent years, has been a chief concern of the U.S. military. While there have been many published studies on the topic, conspicuously absent are studies that have included reserve military personnel. To fill this gap, this study reports descriptive statistics of personnel information and events surrounding 706 Army National Guard suicides that had occurred from 2007 through 2014. Comparative personnel information for random samples of nonsuicides for similar years (8 years, 1,000 cases per year) allowed examining factors associated most with suicide. Findings were very similar to those observed in the active duty Army and civilian populations. Primary risk factors for suicide were as follows: age (young), gender (male), and race/ethnicity (White). Most suicides occurred in nonmilitary status (86%) involving personal firearms (72%). Most frequent events surrounding the suicide were as follows: poor military performance (36% of all suicides), parent-family relationship problems (28%), substance abuse (27%), past behavioral health problem (20%), current behavioral health problems (10%), income problems (22%), and full-time employment problems (18%). Implications of findings for suicide prevention are discussed. PMID- 27388142 TI - Protective role of apigenin in cisplatin-induced renal injury. AB - This study aimed to investigate the effects and molecular mechanisms of the effects of apigenin on cisplatin (CP)-induced kidney injury in mice. Apigenin was intraperitoneally administered for 3 consecutive days before CP treatment. We found that apigenin pretreatment significantly attenuated the damage to the kidneys and decreased the levels of serum creatinine, blood urea nitrogen (BUN), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), which were increased by CP. Apigenin significantly decreased the levels of TNF-alpha, IL 1beta and TGFbeta in the kidneys. Additionally, apigenin inhibited the activations of CYP2E1, phospho-NF-kappaB p65 and phospho-P38 MAPK in CP-induced renal injury. These results suggest that the renoprotective effects of apigenin may be related to the suppressions of oxidative stress and inflammation in CP induced renal injury in mice. PMID- 27388143 TI - Inhibition of human equilibrative nucleoside transporters by 4-((4-(2 fluorophenyl)piperazin-1-yl)methyl)-6-imino-N-(naphthalen-2-yl)-1,3,5-triazin-2 amine. AB - Equilibrative nucleoside transporters (ENTs) play a crucial role in the transport of nucleoside and nucleoside analogues, which are important for nucleotide synthesis and chemotherapy. In addition, ENTs regulate extracellular adenosine levels in the vicinity of its receptors and hence influence adenosine-related functions. The clinical applications of ENT inhibitors in the treatment of cardiovascular diseases and cancer therapy have been explored in numerous studies. However, all ENT inhibitors to date are selective for ENT1 but not ENT2. In the present study, we investigated the novel compound 4-((4-(2 fluorophenyl)piperazin-1-yl)methyl)-6-imino-N-(naphthalen-2-yl)-1,3,5-triazin-2 amine (FPMINT) as an inhibitor of ENT1 and ENT2. Nucleoside transporter-deficient PK15NTD cells stably expressing ENT1 and ENT2 showed that FPMINT inhibited [3H]uridine and [3H]adenosine transport through both ENT1 and ENT2 in a concentration-dependent manner. The IC50 value of FPMINT for ENT2 was 5-10-fold less than for ENT1, and FPMINT could not be displaced with excess washing. Kinetic studies revealed that FPMINT reduced Vmax of [3H]uridine transport in ENT1 and ENT2 without affecting KM. Therefore, we conclude that FPMINT inhibits ENTs in an irreversible and non-competitive manner. Although already selective for ENT2 over ENT1, further modification of the chemical structure of FPMINT may lead to even better ENT2-selective inhibitors of potential clinical, physiological and pharmacological importance. PMID- 27388141 TI - Glucocorticoid therapy and ocular hypertension. AB - The projected number of people who will develop age-related macular degeneration in estimated at 2020 is 196 million and is expected to reach 288 million in 2040. Also, the number of people with Diabetic retinopathy will grow from 126.6 million in 2010 to 191.0 million by 2030. In addition, it is estimated that there are 2.3 million people suffering from uveitis worldwide. Because of the anti-inflammatory properties of glucocorticoids (GCs), they are often used topically and/or intravitreally to treat ocular inflammation conditions or edema associated with macular degeneration and diabetic retinopathy. Unfortunately, ocular GC therapy can lead to severe side effects. Serious and sometimes irreversible eye damage can occur as a result of the development of GC-induced ocular hypertension causing secondary open-angle glaucoma. According to the world health organization, glaucoma is the second leading cause of blindness in the world and it is estimated that 80 million will suffer from glaucoma by 2020. In the current review, mechanisms of GC-induced damage in ocular tissue, GC-resistance, and enhancing GC therapy will be discussed. PMID- 27388146 TI - Modulation of Intersystem Crossing Rate by Minor Ligand Modifications in Cyclometalated Platinum(II) Complexes. AB - Photophysical properties of four new platinum(II) complexes comprising extended ppy (Hppy = 2-phenylpyridine) and thpy (Hthpy = 2-(2'-thienyl)pyridine) cyclometalated ligands and acetylacetonate (acac) are reported. Substitution of the benzene ring of Pt-ppy complexes 1 and 2 with a more electron-rich thiophene of Pt-thpy complexes 3 and 4 leads to narrowing of the HOMO-LUMO gap and thus to a red shift of the lowest energy absorption band and phosphorescence band, as expected for low-energy excited states of the intraligand/metal-to-ligand charge transfer character. However, in addition to these conventional spectral shifts, another, at first unexpected, substitution effect occurs. Pt-thpy complexes 3 and 4 are dual emissive showing fluorescence about 6000 cm(-1) (~0.75 eV) higher in energy relative to the phosphorescence band, while for Pt-ppy complexes 1 and 2 only phosphorescence is observed. For dual-emissive complexes 3 and 4, ISC rates kISC are estimated to be in order of 10(9)-10(10) s(-1), while kISC of Pt-ppy complexes 1 and 2 is much faster amounting to 10(12) s(-1) or more. The relative intensities of the fluorescence and phosphorescence signals of Pt-thpy complexes 3 and 4 depend on the excitation wavelength, showing that hyper-intersystem crossing (HISC) in these complexes is observably significant. PMID- 27388145 TI - Effects of shrub encroachment on soil organic carbon in global grasslands. AB - This study aimed to evaluate the effect of shrub encroachment on soil organic carbon (SOC) content at broad scales and its controls. We conducted a meta analysis using paired control data of shrub-encroached grassland (SEG) vs. non SEG collected from 142 studies worldwide. SOC contents (0-50 cm) were altered by shrub encroachment, with changes ranging from -50% to + 300%, with an effect size of 0.15 (p < 0.01). The SOC contents increased in semi-arid and humid regions, and showed a greater rate of increase in grassland encroached by leguminous shrubs than by non-legumes. The SOC content decreased in silty and clay soils but increased in sand, sandy loam and sandy clay loam. The SOC content increment was significantly positively correlated with precipitation and temperature as well as with soil bulk density but significantly negatively correlated with soil total nitrogen. We conclude the main effects of shrub encroachment would be to increase topsoil organic carbon content. As structural equation model revealed, soils properties seem to be the primary factors responsible for the extent of the changes, coarse textured soils having a greater capacity than fine textured soils to increase the SOC content. This increased effect appears to be secondarily enhanced by climate and plant elements. PMID- 27388144 TI - A Child's HLA-DRB1 genotype increases maternal risk of systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) disproportionately affects women of reproductive age. During pregnancy, women are exposed to various sources of fetal material possibly constituting a significant immunologic exposure relevant to the development of SLE. The objective of this study was to investigate whether having any children who carry DRB1 alleles associated with SLE increase the risk of maternal SLE. This case-control study is based on the University of California, San Francisco Mother-Child Immunogenetic Study and from studies at the Inova Translational Medicine Institute. Analyses were conducted using data for 1304 mothers (219 cases/1085 controls) and their respective 1664 children. We selected alleles based on their known association with risk of SLE (DRB1*03:01, *15:01, or *08:01) or Epstein-Barr virus (EBV) glycoproteins (*04:01) due to the established EBV association with SLE risk. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each allele of interest, taking into account maternal genotype and number of live births. We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers. Increased risk was only present among mothers who were positive for one or more SLE risk-associated alleles (*03:01, *15:01 and/or *08:01). We did not find increased risk of maternal SLE associated with any other tested allele. These findings support the hypothesis that a child's alleles inherited from the father influence a mother's subsequent risk of SLE. PMID- 27388147 TI - Improving testing for hepatitis B before treatment with rituximab. AB - AIMS/OBJECTIVES/BACKGROUND: Individuals with current or previous infection with the hepatitis B virus (HBV) can experience viral reactivation when treated with immunosuppression. Rituximab, an anti-CD20 antibody used to treat many diseases, has potent immunosuppressant effects with a high risk of causing HBV reactivation. Reactivation can range from elevated liver enzymes to acute severe hepatitis with liver failure and a significant mortality risk. HBV screening and appropriate use of prophylactic antiviral therapy can prevent reactivation. This work describes the introduction of a local policy for HBV testing in patients before rituximab treatment and assesses its impact. METHODS AND RESULTS: A baseline review (before policy introduction) of 90 patients showed that only 21 (23%) had hepatitis B surface antigen (HBsAg) and 17 (19%) had hepatitis B core antibody (anti-HBcAb) tested before receiving rituximab. Following introduction of the policy (on the basis of international guidelines), improved laboratory reporting protocols and targeted education sessions, two further reviews of HBV testing rates among patients being initiated onto rituximab were performed. There was a marked increase in pre-rituximab testing for HBsAg from 23 to 79% and for anti-HBcAb from 19 to 78%. Throughout the study period, a total of one (0.8%) HBsAg-positive and six (4.7%) anti-HBcAb-positive patients were identified. CONCLUSIONS: This work clearly indicates that simple strategies can markedly improve appropriate HBV screening. In our cohort, 6% (of whom only 43% had recognized HBV risk factors) required antiviral prophylaxis, which emphasizes the importance of universal screening before rituximab. Reinforcement of the guidelines and ongoing education is needed to further increase testing rates. PMID- 27388148 TI - Effects of butylated hydroxyanisole on the steroidogenesis of rat immature Leydig cells. AB - Butylated hydroxyanisole (BHA) is a synthetic antioxidant used for food preservation. Whether BHA affects testosterone biosynthesis is still unclear. The effects of BHA on the steroidogenesis in rat immature Leydig cells were investigated. Rat immature Leydig cells were isolated from 35-old-day rats and cultured with BHA (50 MUM) for 3 h in combination with 22R-OH-cholesterol, pregnenolone, progesterone, androstenedione, testosterone or dihydrotestosterone, and the concentrations of 5alpha-androstanediol and testosterone in the media were measured. Leydig cells were cultured with BHA (0.05-50 MUM) for 3 h. Q-PCR was used to measure the mRNA levels of following genes: Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1 and Akr1c14. The testis microsomes were prepared to detect the direct action of BHA on 3beta-hydroxysteroid dehydrogenase 1 (HSD3B1), 17alpha-hydroxylase (CYP17A1) and 17beta-hydroxysteroid dehydrogenase 3 activities. In Leydig cells, BHA (50 MUM) significantly inhibited LH- and 8Br cAMP-mediated androgen production. BHA directly inhibited rat testis CYP17A1 and HSD3B1 activities. At 50 MUM, it also reduced the expression levels of Hsd17b3 and Srd5a1 and their protein levels. In conclusion, BHA directly inhibits the activities of CYP17A1 and HSD3B1, and the expression levels of Hsd17b3 and Srd5a1, leading to the lower production of androgen in Leydig cells. PMID- 27388149 TI - Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: A voxel-based morphometric and fMRI study of the whole brain. AB - The primary aim of this study was to identify structural and functional abnormalities in the brains of obsessive-compulsive disorder (OCD) patients. Another aim was to assess the effect of serotonin selective reuptake inhibitors (SSRIs) on brain structure of OCD patients. All subjects underwent brain magnetic resonance imaging (MRI) and resting functional MRI (fMRI). High-resolution three dimensional images were processed using the voxel-based morphometry (VBM) method. The final analysis included 18 OCD patients and 16 healthy controls. In the OCD patients there was a decrease in gray matter volume in the bilateral cingulate cortex and bilateral striatum. In some cortical structures including the cerebellar anterior lobe, left orbital frontal gyrus, right middle frontal gyrus, left middle temporal gyrus, precentral gyrus, and postcentral gyrus, there was an increase in gray matter volume. On fMRI the OCD patients had overactivation of the right cerebellum and right parietal lobe and reduced activation of the left cingulate gyrus, putamen, and caudate nucleus. Eleven OCD patients who improved during 12 weeks of drug treatment with sertraline hydrochloride had a significant increase in gray matter volume in several brain structures but no significant differences were found on resting fMRI. The results indicated a consistent trend between structural and functional images. Higher cortical structures showed increased gray matter volume and increased activation as did the cerebellum whereas subcortical structures showed decreased gray matter volume and decreased activation. And brain structure improvement consisted with symptom improvement after SSRIs treatment in OCD patients. PMID- 27388151 TI - Correlation between Soft X-ray Absorption and Emission Spectra of the Nitrogen Atoms within Imidazolium-Based Ionic Liquids. AB - Soft X-ray absorption spectroscopy (XAS) has been performed on the N K-edge of two imidazolium-based ionic liquids (ILs), 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([C2mim][TFSA]) and 1-ethyl-3-methylimidazolium bromide ([C2mim][Br]), to clarify the electronic structures of the ILs. Soft X ray emission spectroscopy (XES) has also been applied to the ILs by excitation at various X-ray energies according to the XAS spectra. It was possible to fully associate the XAS peaks with the XES peaks. Additionally, both XAS and XES spectra of the ILs were well reproduced by the theoretical spectra for a single molecule model on [C2mim](+) and [TFSA](-) using density functional theory. The assignments for the XAS and XES peaks of the ILs were accomplished from both experimental and theoretical approaches. The theoretical XAS and XES spectra of [C2mim](+) and [TFSA](-) did not significantly depend on the conformations of the ions. The reproducibility of the theoretical spectra for the single-molecule model suggested that the interactions between the cations and anions are very weak in the ILs, thus scarcely influencing the electronic structures of the nitrogen atoms. PMID- 27388150 TI - The essential role of hippocampal alpha6 subunit-containing GABAA receptors in maternal separation stress-induced adolescent depressive behaviors. AB - Exposure to early stressful adverse life events such as maternal separation severely impacts the development of the nervous system. Using immunohistochemistry, quantitative PCR and Western blot approaches, we found that alpha6 subunit-containing GABAA receptors (Gabra6-containing GABAA Rs) were expressed on hippocampal interneurons of adolescent rats. Maternal separation stress (MS) from postnatal day 2 to15 significantly reduced Gabra6 expression and provoked depressive behaviors such as anhedonia. Furosemide, the selective antagonist of Gabra6-containing GABAARs, strongly increased peak amplitude of evoked IPSCs at CA3-CA1 synapses and the frequency of miniature IPSPs recorded from CA1 pyramidal cells in naive control animals, and this effect was occluded in MS animals. Knockdown of Gabra6 expression in hippocampus mimicked furosemide's effect and was sufficient to produce similar depressive symptoms that were observed in MS animals. These results indicate that the Gabra6 containing GABAA R is a key modulator of hippocampal synaptic transmission and likely plays a crucial role in the pathophysiology of maternal separation-induced depression. PMID- 27388152 TI - Characterization of the Xylella fastidiosa PD1311 gene mutant and its suppression of Pierce's disease on grapevines. AB - Xylella fastidiosa causes Pierce's disease (PD) on grapevines, leading to significant economic losses in grape and wine production. To further our understanding of X. fastidiosa virulence on grapevines, we examined the PD1311 gene, which encodes a putative acyl-coenzyme A (acyl-CoA) synthetase, and is highly conserved across Xylella species. It was determined that PD1311 is required for virulence, as the deletion mutant, DeltaPD1311, was unable to cause disease on grapevines. The DeltaPD1311 strain was impaired in behaviours known to be associated with PD development, including motility, aggregation and biofilm formation. DeltaPD1311 also expressed enhanced sensitivity to H2 O2 and polymyxin B, and showed reduced survival in grapevine sap, when compared with wild-type X. fastidiosa Temecula 1 (TM1). Following inoculation, DeltaPD1311 could not be detected in grape shoots, which may be related to its altered growth and sensitivity phenotypes. Inoculation with DeltaPD1311 2 weeks prior to TM1 prevented the development of PD in a significant fraction of vines and eliminated detectable levels of TM1. In contrast, vines inoculated simultaneously with TM1 and DeltaPD1311 developed disease at the same level as TM1 alone. In these vines, TM1 populations were distributed similarly to populations in TM1-only inoculated plants. These findings suggest that, through an indirect mechanism, pretreatment of vines with DeltaPD1311 suppresses pathogen population and disease. PMID- 27388153 TI - Slow-release carbohydrates: growing evidence on metabolic responses and public health interest. Summary of the symposium held at the 12th European Nutrition Conference (FENS 2015). AB - To draw attention to the necessity of considering differences in the digestibility of carbohydrates, and more specifically of starch, a symposium was held at the 12th European Nutrition Conference (FENS), which took place in Berlin from October 20 to 23, 2015. The purpose of this session was to present the consolidated knowledge and recent advances regarding the relationship between slow-release carbohydrates, metabolic responses, and public health issues. Three main topics were presented: 1) the definition of, sources of, and recognised interest in the glycaemic response to slowly digestible starch (SDS); 2) clinical evidence regarding the physiological effects of slow-release carbohydrates from cereal foods; and 3) interest in reducing the postprandial glycaemic response to help prevent metabolic diseases. Foods with the highest SDS content induce the lowest glycaemic responses, as the starch is protected from gelatinisation during processing. In humans, high-SDS food consumption induces slower glucose release, lower postprandial insulinaemia, and stimulation of gut hormones. Moreover, postprandial hyperglycaemia is an independent risk factor for type two diabetes mellitus (T2DM) and cardiovascular disease (CVD). Therefore, given the plausible aetiologic mechanisms, we argue that postprandial glucose levels are relevant for health and disease and represent a meaningful target for intervention, for example, through dietary factors. This symposium was organised by Mondelez International R&D. PMID- 27388154 TI - Transcriptome and Degradome of microRNAs and Their Targets in Response to Drought Stress in the Plants of a Diploid and Its Autotetraploid Paulownia australis. AB - MicroRNAs (miRNAs) are small, non-coding RNAs that play vital roles in plant growth, development, and stress response. Increasing numbers of studies aimed at discovering miRNAs and analyzing their functions in plants are being reported. In this study, we investigated the effect of drought stress on the expression of miRNAs and their targets in plants of a diploid and derived autotetraploid Paulownia australis. Four small RNA (sRNA) libraries and four degradome libraries were constructed from diploid and autotetraploid P. australis plants treated with either 75% or 25% relative soil water content. A total of 33 conserved and 104 novel miRNAs (processing precision value > 0.1) were identified, and 125 target genes were identified for 36 of the miRNAs by using the degradome sequencing. Among the identified miRNAs, 54 and 68 were differentially expressed in diploid and autotetraploid plants under drought stress (25% relative soil water content), respectively. The expressions of miRNAs and target genes were also validated by quantitative real-time PCR. The results showed that the relative expression trends of the randomly selected miRNAs were similar to the trends predicted by Illumina sequencing. And the correlations between miRNAs and their target genes were also analyzed. Furthermore, the functional analysis showed that most of these miRNAs and target genes were associated with plant development and environmental stress response. This study provided molecular evidence for the possible involvement of certain miRNAs in the drought response and/or tolerance in P. australis, and certain level of differential expression between diploid and autotetraploid plants. PMID- 27388155 TI - CYP2B6rs2279343 Is Associated with Improved Survival of Pediatric Rhabdomyosarcoma Treated with Cyclophosphamide. AB - BACKGROUND: Rhabdomyosarcoma (RMS) is a small round blue cell malignant tumor, representing 7% of childhood malignancies, and over 50% of all soft tissue sarcomas. Cyclophosphamide (CPA) is a prodrug and is the mainstay of RMS treatment. CYP2B6 is a highly polymorphic drug metabolizing enzyme involved in CPA bioactivation. The influence of CYP2B6 single nucleotide polymorphisms (SNPs) on the survival of RMS is still unknown. METHODS: We genotyped CYP2B6SNPs rs2279343, rs3745274, and rs3211371 by restriction fragment polymorphism (RFLP) after PCR amplification in a cohort of 73 pediatric RMS patients treated with CPA based first line treatment. We then analyzed the association between those genotypes and survival outcome of RMS. RESULTS: The frequencies of CYP2B6 rs2279343, rs3745274, and rs3211371 were 63%, 45.2%, and 5.5%, respectively. There was no association between rs3745274, rs3211371 genotypes and survival outcomes of RMS. However, the carriers of at least one mutant allele CYP2B6rs2279343 had significantly longer event-free survival (p-value = 0.03). CONCLUSION: Our results demonstrated that CYP2B6 rs2279343 may predict EFS in RMS patients and warrants future studies to clarify the pharmacogenetics of CPA in pediatrics. If validated, integration of genetic factors with clinical and molecular characteristics could be used for a composite algorithm to better stratify risk prior to treatment. PMID- 27388156 TI - Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients. AB - BACKGROUND: The suppressive effect of mesenchymal stromal/stem cells (MSCs) on diverse immune cells is well known, but it is unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of cytokine secretion. METHODS: Human MSCs were generated from bone marrow and nasal mucosa. NK cells were isolated from peripheral blood of healthy volunteers or of immunocompromised patients after severe injury. NK cells were cultured with MSCs or with MSC-derived conditioned media in the absence or presence of IL-12 and IL 18. C-C chemokine receptor (CCR) 2, C-C chemokine ligand (CCL) 2, and the interferon (IFN)-gamma receptor was blocked by specific inhibitors or antibodies. The synthesis of IFN-gamma and CCL2 was determined. RESULTS: In the absence of exogenous cytokines, trace amounts of NK cell-derived IFN-gamma licensed MSCs for enhanced synthesis of CCL2. In turn, MSCs primed NK cells for increased release of IFN-gamma in response to IL-12 and IL-18. Priming of NK cells by MSCs occurred in a cell-cell contact-independent manner and was impaired by inhibition of the CCR2, the receptor of CCL2, on NK cells. CD56(bright) NK cells expressed higher levels of CCR2 and were more sensitive to CCL2-mediated priming by MSCs and by recombinant CCR2 ligands than cytotoxic CD56(dim) NK cells. NK cells from severely injured patients were impaired in cytokine-induced IFN-gamma synthesis. Co-culture with MSCs or with conditioned media from MSCs and MSC/NK cell co cultures from healthy donors improved the IFN-gamma production of the patients' NK cells in a CCR2-dependent manner. CONCLUSIONS: A positive feedback loop driven by NK cell-derived IFN-gamma and MSC-derived CCL2 increases the inflammatory response of cytokine-stimulated NK cells not only from healthy donors but also from immunocompromised patients. Therapeutic application of MSCs or their soluble factors might thus improve the NK function after severe injury. PMID- 27388157 TI - Bioinformatics Prediction of Polyketide Synthase Gene Clusters from Mycosphaerella fijiensis. AB - Mycosphaerella fijiensis, causal agent of black Sigatoka disease of banana, is a Dothideomycete fungus closely related to fungi that produce polyketides important for plant pathogenicity. We utilized the M. fijiensis genome sequence to predict PKS genes and their gene clusters and make bioinformatics predictions about the types of compounds produced by these clusters. Eight PKS gene clusters were identified in the M. fijiensis genome, placing M. fijiensis into the 23rd percentile for the number of PKS genes compared to other Dothideomycetes. Analysis of the PKS domains identified three of the PKS enzymes as non-reducing and two as highly reducing. Gene clusters contained types of genes frequently found in PKS clusters including genes encoding transporters, oxidoreductases, methyltransferases, and non-ribosomal peptide synthases. Phylogenetic analysis identified a putative PKS cluster encoding melanin biosynthesis. None of the other clusters were closely aligned with genes encoding known polyketides, however three of the PKS genes fell into clades with clusters encoding alternapyrone, fumonisin, and solanapyrone produced by Alternaria and Fusarium species. A search for homologs among available genomic sequences from 103 Dothideomycetes identified close homologs (>80% similarity) for six of the PKS sequences. One of the PKS sequences was not similar (< 60% similarity) to sequences in any of the 103 genomes, suggesting that it encodes a unique compound. Comparison of the M. fijiensis PKS sequences with those of two other banana pathogens, M. musicola and M. eumusae, showed that these two species have close homologs to five of the M. fijiensis PKS sequences, but three others were not found in either species. RT-PCR and RNA-Seq analysis showed that the melanin PKS cluster was down-regulated in infected banana as compared to growth in culture. Three other clusters, however were strongly upregulated during disease development in banana, suggesting that they may encode polyketides important in pathogenicity. PMID- 27388158 TI - Interstitial pneumonia and pulmonary hypertension associated with suspected ehrlichiosis in a dog. AB - BACKGROUND: In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described. However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known. Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process. PH is often irreversible, but can be reversible if it is secondary to a treatable underlying etiology. CME is currently not generally recognized as one of the possible diseases leading to interstitial pneumonia and secondary PH in dogs. Only one case of PH associated with CME has been reported worldwide. CASE PRESENTATION: A seven-year-old, male intact, mixed breed dog was presented with 2 weeks history of lethargy and dyspnea. The dog previously lived in the Cape Verdean islands. Physical examination showed signs of right-sided congestive heart failure and poor peripheral perfusion. Thoracic radiography showed moderate right-sided cardiomegaly with dilation of the main pulmonary artery and a mild diffuse interstitial lung pattern with peribronchial cuffing. Echocardiography showed severe pulmonary hypertension with an estimated pressure gradient of 136 mm Hg. On arterial blood gas analysis, severe hypoxemia was found and complete blood count revealed moderate regenerative anemia and severe thrombocytopenia. A severe gamma hyperglobulinemia was also documented. Serology for Ehrlichia canis was highly positive. Treatment with oxygen supplementation, a typed packed red blood cell transfusion and medical therapy with doxycycline, pimobendan and sildenafil was initiated and the dog improved clinically. Approximately 2 weeks later, there was complete resolution of all clinical signs and marked improvement of the PH. CONCLUSION: This report illustrates that CME might be associated with significant pulmonary disease and should be considered as a possible differential diagnosis in dogs presenting with dyspnea and secondary pulmonary hypertension, especially in dogs that have been in endemic areas. This is important because CME is a treatable disease and its secondary lung and cardiac manifestations may be completely reversible. PMID- 27388159 TI - Utilization and evaluation of noncore chemotherapy regimens within an academic medical center. AB - Uniformity of evidence-based chemotherapy prescribing using approved, standard, or "core" regimens provides systems-based safety. Noncore chemotherapy regimens are non-standard-of-care regimens requested by physicians on a patient-by-patient basis. Chemotherapy Council, a Pharmacy & Therapeutics subcommittee, assesses all requests and determines approval status based upon submitted evidence and patient specific factors. This study's purpose is to describe noncore chemotherapy regimens utilization, efficacy, and clinical outcomes in patients receiving noncore chemotherapy regimens. This retrospective chart review includes a two stage utilization and outcomes evaluation of patients receiving noncore chemotherapy regimens. Stage I, a demographics and utilization assessment of patients receiving noncore chemotherapy regimens, has data collection including patient age, sex, performance score, malignancy, and noncore chemotherapy regimen use justification. Stage II assesses noncore chemotherapy regimen-related, patient-specific outcomes of breast cancer noncore chemotherapy regimen patients. Breast cancer patients were evaluated on regimen and clinical outcomes including disease stage, regimen duration, discontinuation reason, subsequent chemotherapy, survival, and time from noncore chemotherapy regimen until death. Within stage I, 307 patient-specific noncore chemotherapy regimen requests were submitted. The most commonly submitted rationale was modification of a core regimen (33%), followed by patient-specific factors (29%) and salvage therapy (22%). For stage II, 29 breast cancer patients received a noncore chemotherapy regimen and most (54%) received a modified core regimen. The vast majority of noncore chemotherapy regimen discontinuation was due to either regimen completion (42%) or disease progression (42%). Nonelective hospitalizations (35%) and mortality (30%) were found during the median 13.3 months of follow up. Noncore chemotherapy regimen use provides regimen tailoring for patients who are candidates for further therapy, but nonelective hospitalizations, end-of-life chemotherapy, and mortality warrant further investigation to improve patient outcomes. PMID- 27388161 TI - Adherence to On-Time ART Drug Pick-Up and Its Association with CD4 Changes and Clinical Outcomes Amongst HIV Infected Adults on First-Line Antiretroviral Therapy in Nigerian Hospitals. AB - Medication adherence is a major determinant of antiretroviral treatment (ART) success. Promptness in medication refill pick-ups may give an indication of medication adherence. This study determined medication refill adherence among HIV positive patients on ART and its association with treatment outcomes in HIV treatment centers in Nigeria. This retrospective multi-center cohort study involved a review of ART refill records for 3534 HIV-positive patients aged 18-60 years who initiated first-line ART between January 2008 and December 2009 and were on therapy for >=18 months after ART initiation. Drug refill records of these patients for 10 consecutive refill visits after ART initiation were analyzed. The first ten consecutive refill appointment-keeping rates after ART initiation ranged from 64.3 % to 76.1 % which decreased with successive visits. Altogether, 743 (21.1 %) patients were deemed adherent, meaning they picked up their drugs within 7 days of the drug refill appointment date on at least nine out of ten refill visits. The adherent group of patients had a mean CD4 cells increase of 206 +/- 6.1 cells/dl after 12 months of ART compared to 186 +/- 7.1 cells/dl reported among the nonadherent group (p = 0.0145). The proportion of patients in the adherent category who showed no OIs after 12 months on ART (81 %) was significantly higher when compared to the proportion in the non-adherent category (23.5 %), (p = 0.008). The multivariate analysis showed that the odds of being adherent was 2-3 times more in patients who had a baseline CD4 count of less than 200 cells/dl compared to those with a baseline CD4 of >350 cells/dl. (AOR 2.43, 95 % CI 1.62-3.66). In addition, for patients with baseline CD4 cell count of 201-350 cells/dl, the odds of being adherent was found to be 1.9 compared to those with baseline CD4 of greater than 350 cells/dl (AOR 1.93, 95 % CI 1.27-2.94). Pharmacy refill data can serve as an adherence measure. Adherence to on-time drug pickup on >=90 % of refill appointments was associated with a better CD4 count response and a reduction in the presence of opportunistic infections in ART patients after 12 months of treatment. PMID- 27388160 TI - Pain is Associated with Missed Clinic Visits Among HIV-Positive Women. AB - Pain is highly prevalent among HIV-positive individuals, with women representing a large subset of those with pain. However, little is known about the relationship between pain and retention in HIV medical care. Among a cohort of HIV-positive women of color, we evaluated the association between pain and retention in care, as measured by missed clinic visits. The Health Resources and Services Administration's Women of Color Initiative was a multi-site observational cohort study evaluating demonstration projects to engage HIV positive women in medical care. From November 2010 to July 2013, 921 women were enrolled in the study across nine U.S. sites; baseline interviews collected data on socio-demographic, clinical, and risk behavior characteristics. Pain was assessed at baseline based on number of days in pain over the last 30 days and was categorized as no pain (0 days), infrequent pain (1-13 days), and frequent pain (14-30 days), with 14 days being the median. Missed visits over the one-year follow-up period, evaluated by chart abstraction, were dichotomized as <=1 missed visit versus >1 missed visit. We conducted multivariate logistic regression to assess the association between pain at baseline and missed visits, adjusting for pertinent covariates. Among our sample (N = 862), 52.2 % of women reported no pain, 23.7 % reported infrequent pain and 24.1 % reported frequent pain. Forty five percent had >1 missed visit during the one-year follow-up period. Overall, we did not find a significant association between pain and missed visits (aOR 2.30; 95 % CI 1.00-5.25). However, in planned stratified analyses, among women reporting current substance use at baseline, reporting frequent pain was associated with a higher odds of missed visits as compared with reporting no pain (aOR 15.14; 95 % CI 1.78-128.88). In our overall sample, pain was not significantly associated with missed visits. However, frequent pain was associated with missed visits among HIV-positive women of color who reported substance use at baseline. A better understanding of the relationship between pain and missed visits could guide efforts to improve retention in care in this population. PMID- 27388162 TI - Developing Activity Localization Fluorescence Peptide Probe Using Thiol-Ene Click Reaction for Spatially Resolved Imaging of Caspase-8 in Live Cells. AB - Small molecule probes suitable for high-resolution fluorescence imaging of enzyme activity pose a challenge in chemical biology. We developed a novel design of activity localization fluorescence (ALF) peptide probe, which enables spatially resolved, highly sensitive imaging of peptidase in live cells. The ALF probe was synthesized by a facile thiol-ene click reaction of a cysteine-appended peptide with an acryloylated fluorophore. Upon cleavage by peptidase, the probe undergoes a seven-membered intramolecular cyclization and releases the fluorophore with the excited-state intramolecular photon transfer (ESIPT) effect. A highly fluorescent, insoluble aggregate was formed around the enzyme, which facilitates high-sensitivity and high-resolution imaging. This design is demonstrated for detection of caspase-8 activation. The results show that our design allows easy, high-yield synthesis of the probe, and the probe affords high sensitivity for caspase-8 detection. Live cell imaging reveals that the probe is able to render highly localized and high-contrast fluorescence signal for caspase-8. Our design holds the potential as a generally applicable strategy for developing high sensitivity and high-resolution imaging peptide probes in cell biology and diagnostics. PMID- 27388163 TI - Reply to: "Comment on Probing the Properties of Polynuclear Superhalogens without Halogen Ligand via ab Initio Calculations: A Case Study on Double-Bridged [Mg2 (CN)5 ](-1) Anions by Li et al. ". PMID- 27388164 TI - Coating of intravascular balloon with paclitaxel prevents constrictive remodeling of the dilated porcine femoral artery due to inhibition of intimal and media fibrosis. AB - Here we investigated how a coating of intravascular balloon with paclitaxel (drug coated balloon; DCB, FreewayTM) impacted porcine peripheral artery vascular function and remodeling. Domestic swine (n = 54) underwent percutaneous overstretch balloon dilation of femoral and iliac arteries, controlled by angiography and optical coherence tomography (OCT). Paclitaxel tissue uptake was measured at 1 h and 1, 3, and 9 days post-dilation. At these time-points and at 32 +/- 2 days, vascular function of the dilated arteries was assessed using the organ chamber model. Neointimal growth and remodeling indices were determined using OCT and histology at 32 +/- 2 days. Intima and media fibrosis were quantified by picrosirius red staining. Post-inflation femoral artery tissue drug levels were 460 +/- 214, 136 +/- 123, 14 +/- 6, and 0.1 +/- 0.1 ng/mg at 1 h and 1, 3, and 9 days, respectively. Compared to plain balloon, FreewayTM resulted in a significantly smaller neointimal area (P < 0.05), less tunica intima (8.0 +/- 5.4 vs 14.2 +/- 4.7 %) and media fibrosis (15.6 +/- 7.7 vs 24.5 +/- 5.4 %), and less femoral artery constrictive remodeling (remodeling index: 1.08 +/- 0.08 vs 0.94 +/- 0.08). The DCB was associated with significantly increased vasoconstrictor tone and endothelium-dependent vasodilation impairment shortly after post-overstretch injury. Overall, DCB dilation of peripheral arteries resulted in high drug uptake into arterial tissue. Compared with the plain balloon, the DCB was associated with decreased vessel wall fibrosis after balloon overstretch injury, and reduced degrees of constrictive remodeling and neointimal hyperplasia. PMID- 27388165 TI - Low absolute CD4+ T cell counts in peripheral blood are associated with inferior survival in follicular lymphoma. AB - Host immunity and tumor microenvironment significantly influence follicular lymphoma (FL) outcomes. Lymphopenia has been identified as a negative prognostic factor for FL. However, there is limited data regarding prognostic value of peripheral blood T lymphocyte subsets, especially absolute CD4+ T cell counts (ACD4C) in FL. We studied 127 consecutive FL patients to investigate whether peripheral blood ACD4C or absolute monocytes (AMC) at diagnosis had an impact on FL prognosis. In our cohort, both low ACD4C and high AMC were the parameters associated with inferior progression-free survival (PFS) (P = 0.021 and P = 0.013, respectively) and inferior overall survival (OS) (P = 0.020 and P = 0.005, respectively) by univariate analysis. Multivariate analysis revealed that only low ACD4C was statistically significant in worse PFS (hazard ratio, 2.811; 95 % confidence interval, 1.137-6.950; P = 0.025) and shorter OS (hazard ratio, 3.393; 95 % confidence interval, 1.037-11.105; P = 0.043) independent of FLIPI-2. Evaluation of blood ACD4C could be a useful indicator of outcome in previously untreated FL patients. PMID- 27388166 TI - A Comprehensive Analysis on Spread and Distribution Characteristic of Antibiotic Resistance Genes in Livestock Farms of Southeastern China. AB - The pollution of antibiotic resistance genes (ARGs) in livestock farms is a problem which need to be paid more attention to, due to the severe resistance dissemination and the further human health risk. In this study, all the relevant exposure matrices (manure, soil and water) of sixteen animal farms in Southeastern China were sampled to determine twenty-two ARGs conferring resistance to five major classes of antibiotics including tetracyclines, sulfonamides, quinolones, aminoglycosides, and macrolides. The results showed that the spread property of sul genes was most extensive and strong, followed by tet and erm genes. The abundance of tet genes expressing ribosomal protection proteins (tetM, tetO, tetQ, tetT and tetW) was higher than that expressing efflux pump proteins (tetA, tetC, tetE and tetG) in each type of samples. The high abundance and frequency of ermB gene in the matrices should be paid more attention, because macrolides is a major medicine for human use. For manures, it was found that the similar ARGs distribution rules were existing in poultry manure or porcine manure samples, despite of the different origins of these two types of livestock farms. Meanwhile, it was interesting that the distribution rule of tet genes in animal manure was nearly the same as all the ARGs. For soils, the result of nonmetric multi-dimensional scaling (NMDS) analysis showed that the pollution of ARGs in the soils fertilized by poultry and cattle manures were more substantial in northern Jiangsu, but no significant ARGs diversity was observed among porcine manured soils of five different regions. Furthermore, most ARGs showed significant positive relationships with environmental variables such as concentration of sulfonamides, tetracyclines, Cu, Zn and total organic carbon (TOC). The pollution profile and characteristics of so many ARGs in livestock farms can provide significative foundation for the regulation and legislation of antibiotics in China. PMID- 27388168 TI - Erratum to: Safety and efficacy of an E2 glycoprotein subunit vaccine produced in mammalian cells to prevent experimental infection with bovine viral diarrhoea virus in cattle. PMID- 27388167 TI - Influence of emotional stimulus valence on inhibitory control in adults with and without ADHD. AB - Human behavior is influenced both by approach and avoidance automatic reactions to positive and negative stimulus, respectively, but these reactions have not been well studied in attention-deficit/hyperactivity disorder (ADHD) patients. Moreover, studies employing spatial stimulus-response compatibility tasks in ADHD and healthy control (HC) subjects are scarce and inconclusive. The present study investigated inhibitory control and emotional processing in ADHD adults with a modified stimulus-response compatibility task in which spatial and emotional features of affective stimuli had to be processed together to select the correct response. Manual responses to figures of Favorite and Rival soccer team players were measured, and compatible or incompatible responses were chosen according to the soccer team figure. Eighteen HC participants and sixteen ADHD adults performed the task. We found an ordinary spatial compatibility effect for the Favorite soccer team and a reversed one for the Rival team in the ADHD group but not in the HC group. The effects may be due to stronger approach and withdrawal reactions toward the Favorite soccer team and away from the Rival one, respectively, indicating poor inhibitory control for the ADHD group. These results show that differences between ADHD and HC subjects become prominent when response selection involves both emotional and spatial features of the stimulus. PMID- 27388170 TI - [Not Available]. PMID- 27388169 TI - Ticks infesting domestic dogs in the UK: a large-scale surveillance programme. AB - BACKGROUND: Recent changes in the distribution of tick vectors and the incidence of tick-borne disease, driven variously by factors such as climate change, habitat modification, increasing host abundance and the increased movement of people and animals, highlight the importance of ongoing, active surveillance. This paper documents the results of a large-scale survey of tick abundance on dogs presented to veterinary practices in the UK, using a participatory approach that allows relatively cost- and time-effective extensive data collection. METHODS: Over a period of 16 weeks (April-July 2015), 1094 veterinary practices were recruited to monitor tick attachment to dogs and provided with a tick collection and submission protocol. Recruitment was encouraged through a national publicity and communication initiative. Participating practices were asked to select five dogs at random each week and undertake a thorough, standardized examination of each dog for ticks. The clinical history and any ticks were then sent to the investigators for identification. RESULTS: A total of 12,000 and 96 dogs were examined and 6555 tick samples from infested dogs were received. Ixodes ricinus (Linnaeus) was identified on 5265 dogs (89 %), Ixodes hexagonus Leach on 577 (9.8 %) and Ixodes canisuga Johnston on 46 (0.8 %). Ten dogs had Dermacentor reticulatus (Fabricius), one had Dermacentor variabilis (Say), three had Haemaphysalis punctata Canesteini & Fanzago and 13 had Rhipicephalus sanguineus Latreille. 640 ticks were too damaged for identification. All the R. sanguineus and the single D. variabilis were on dogs with a recent history of travel outside the UK. The overall prevalence of tick attachment was 30 % (range 28-32 %). The relatively high prevalence recorded is likely to have been inflated by the method of participant recruitment. CONCLUSION: The data presented provide a comprehensive spatial understanding of tick distribution and species abundance in the UK against which future changes can be compared. Relative prevalence maps show the highest rates in Scotland and south west England providing a valuable guide to tick-bite risk in the UK. PMID- 27388171 TI - [Not Available]. PMID- 27388172 TI - [Not Available]. PMID- 27388173 TI - [Not Available]. PMID- 27388174 TI - [Not Available]. PMID- 27388175 TI - [Not Available]. PMID- 27388176 TI - [Not Available]. PMID- 27388177 TI - [Not Available]. PMID- 27388178 TI - [Not Available]. PMID- 27388179 TI - [Not Available]. PMID- 27388180 TI - [Not Available]. PMID- 27388182 TI - [Not Available]. PMID- 27388181 TI - [Not Available]. PMID- 27388183 TI - [Not Available]. PMID- 27388184 TI - [Not Available]. PMID- 27388186 TI - [Not Available]. PMID- 27388185 TI - [Not Available]. PMID- 27388187 TI - [Not Available]. PMID- 27388188 TI - [Not Available]. PMID- 27388189 TI - [Not Available]. PMID- 27388190 TI - [Not Available]. PMID- 27388191 TI - [Not Available]. PMID- 27388192 TI - [Not Available]. PMID- 27388193 TI - [Not Available]. PMID- 27388195 TI - Early Intervention in Lung Cancers With Rapid Plasma Genotyping for EGFR and KRAS Mutations. PMID- 27388194 TI - Patterns of perspectives on fall-prevention beliefs by community-dwelling older adults: a Q method investigation. AB - BACKGROUND: Falling has high incidence and reoccurrence rates and is an essential factor contributing to accidental injury or death for older adults. Enhancing the participation of community-dwelling older adults in fall-prevention programs is crucial. Understanding fall-prevention beliefs will be beneficial for developing a community-based fall-prevention program. The aim of the present study was to identify the distinct types of subjective views on the fall-prevention beliefs of community-dwelling older adults aged 80 years and older by applying the Q method. METHODS: The Q method was adopted to investigate the pattern of perception on fall-prevention beliefs. Forty-two older adults aged 80 - 92 years from a community care center in Northern Taiwan were recruited and requested to complete a Q-sorting. A series of Q-sorts was performed by the participants to rank 30 statements into a normal distribution Q-sort grid. The Q-sorts were subjected to principal component analysis by using PQMethod software Version 2.35. RESULTS: Four statistically independent perspectives were derived from the analysis and reflected distinct viewpoints on beliefs related to fall prevention. Participants in the Considerate perspective believed that health problems caused by falling were serious and fall prevention could decrease the burden they place on their family. Participants in the Promising perspective believed that existing health problems could cause a fall and that fall prevention contributed to their well being. Participants in the Adaptable perspective perceived low barriers to execute fall prevention and displayed self-confidence and independence in preventing falls. Participants in the Ignorance perspective believed that they could not prevent falls and perceived barriers to fall prevention. CONCLUSIONS: By combining theoretical constructs and the Q methodology approach, this study identified four distinct perspectives on fall prevention among community-dwelling older adults. Critical reflection on older adult personal perspectives and interpretations of the required responsive approach is a key element for appropriating fall-prevention support. PMID- 27388197 TI - Intraosseous Hibernoma in the Sacrum of an Adult. AB - Hibernoma is an uncommon lipomatous tumor composed of brown adipose cells that until recently has only ever been described in soft tissue locations. This report describes the histological features of a discrete lesion in the sacrum of an 84 year-old lady. Biopsy of this lesion demonstrated that it consisted predominantly of multivacuolated lipocytes with a morphological and immunohistochemical profile consistent with brown fat cells. The lesion was diagnosed as an intraosseous hibernoma. This is the 16th report in the English literature of a hibernoma occurring outside of a soft tissue location. PMID- 27388196 TI - Case report: Xanthogranulomutous pyelonephritis presenting as "Wilms' tumor". AB - BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is a rare renal tumor that arises as a complication of chronic obstructive pyelonephritis of uncertain etiology. It is primarily an adult tumor seen occasionally in children associated with urinary tract obstruction due to congenital urological anomalies, nephrolithiasis, and recurrent urinary tract infections. Radiologically, it may show neoplastic features such as those seen in common pediatric renal malignancies like wilms' tumor and renal cell carcinoma. This overlap in radiological manifestation frequently leads to misdiagnosis and delay in appropriate intervention. We report a case of a 3 years old boy who presented with history of recurrent urinary tract infections and a left renal mass initially thought to be Wilms' tumor. CASE PRESENTATION: We present a case of a 3 years old boy admitted to the Pediatric oncology unit at Muhimbli National Hospital in Dar es Salaam, Tanzania with one year history of recurrent fever and urinary tract infection signs and symptoms refractory to antibiotic therapy. He was eventually found to have a left kidney mass detected at the District hospital by abdominal ultrasound performed to evaluate a flank mass that was felt by his mother. He was then referred to our unit for a suspicion of Wilms' tumor which finally turned out to be a left kidney Xanthogranulomatous pyelonephritis. He underwent a successful left nephrectomy and was discharged from hospital in a stable clinical condition and remains asymptomatic at the time of submission of this case report. CONCLUSION: This case report underscores the need for clinicians attending a febrile child with a renal mass that can be confused with common pediatric renal malignancies such as Wilms' tumor to broaden their differential diagnosis. The case also underlines the significance of individualized patient evaluation because this patient would have otherwise received preoperative chemotherapy under the International Society of Pediatric Oncology (SIOP) guidelines if the diagnosis of Wilms tumor was not ruled out. PMID- 27388198 TI - Complete Tissue Submission to Increase Lymph Node Detection in Pelvic Lymph Node Packets Submitted for Patients Undergoing Radical Prostatectomy and Radical Cystectomy. AB - BACKGROUND: Pelvic lymphadenectomy has prognostic and therapeutic implications in both bladder and prostate cancer. Pelvic lymphadenectomy specimens are fatty and identification of lymph nodes (LNs) can be difficult during the grossing process. We investigated the benefit of a new grossing method requiring entire LN packet submission. MATERIALS/METHODS: We introduced a new grossing protocol requiring total submission of LN packets for patients undergoing radical prostatectomy (RP) or radical cystectomy (RC). A retrospective review was performed to evaluate clinical and pathologic data for RP (n = 59) and RC (n = 56) cases performed 18 months prior to and 18 months following implementation of the new lymphadenectomy grossing protocol. RESULTS: For RP and RC cases, significantly more LNs were found when total LN packets were submitted with the new technique: mean 14.1 versus 8.7, and mean 25.2 versus 15.9, respectively ( P = .007, P = .011). For RP cases, there was no significant change in the number of LN packets submitted for evaluation from the operating room ( P = .76). For RC cases, more LNs were found with the new technique despite a significantly fewer number of LN packets sent from the operating room in the cohort that were processed with the new technique: mean 2.2 versus 4.0 LN packets ( P < .001). Significantly more paraffin blocks were required using the new grossing method for both RP and RC: mean 13.53 versus 6.9 and mean 19.0 versus 12.4, respectively ( P < .001, P = .018). CONCLUSIONS: Submitting all additional fatty tissue after palpable identification of LNs can significantly increase the detection of LNs in RP and RC cases. PMID- 27388199 TI - Autoantibodies in Autoimmune Liver Diseases-Methods of Detection and Interpretation: An Update for the Reporting Pathologist. AB - Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation. PMID- 27388200 TI - Biofilm formation and interspecies interactions in mixed cultures of thermo acidophilic archaea Acidianus spp. and Sulfolobus metallicus. AB - The understanding of biofilm formation by bioleaching microorganisms is of great importance for influencing mineral dissolution rates and to prevent acid mine drainage (AMD). Thermo-acidophilic archaea such as Acidianus, Sulfolobus and Metallosphaera are of special interest due to their ability to perform leaching at high temperatures, thereby enhancing leaching rates. In this work, leaching experiments and visualization by microscopy of cell attachment and biofilm formation patterns of the crenarchaeotes Sulfolobus metallicus DSM 6482(T) and the Acidianus isolates DSM 29038 and DSM 29099 in pure and mixed cultures on sulfur or pyrite were studied. Confocal laser scanning microscopy (CLSM) combined with fluorescent dyes as well as fluorescently labeled lectins were used to visualize different components (e.g. DNA, proteins or glycoconjugates) of the aforementioned species. The data indicate that cell attachment and the subsequently formed biofilms were species- and substrate-dependent. Pyrite leaching experiments coupled with pre-colonization and further inoculation with a second species suggest that both species may negatively influence each other during pyrite leaching with respect to initial attachment and pyrite dissolution rates. In addition, the investigation of binary biofilms on pyrite showed that both species were heterogeneously distributed on pyrite surfaces in the form of individual cells or microcolonies. Physical contact between the two species seems to occur, as revealed by specific lectins able to specifically bind single species within mixed cultures. PMID- 27388201 TI - Clinicopathological and prognostic significance of GPX2 protein expression in esophageal squamous cell carcinoma. AB - BACKGROUND: Chaoshan region, a littoral area of Guangdong province in southern China, has a high incidence of esophageal squamous cell carcinoma (ESCC). At present, the prognosis of ESCC is still very poor, therefore, there is urgent need to seek valuable molecular biomarker for prognostic evaluation to guide clinical treatment. GPX2, a selenoprotein, was exclusively expressed in gastrointestinal tract and has an anti-oxidative damage and anti-tumour effect in the progress of tumourigenesis. METHODS: We collected 161 ESCC patients samples, among which 83 patients were followed up. We employed immunochemistry analysis, western blotting and quantitative real-time PCR for measuring the expression of GPX2 within ESCC samples. We analysed the relationship between the expression of GPX2 and clinicopathological parameters of 161 patients with ESCC by Chi-square or Fisher's exact test. The survival analysis of GPX2 expression within ESCC tissues was evaluated by the Kaplan-Meier method and Cox-regression. RESULTS: A significant higher expression level of GPX2 was detected in tumour tissues compared to that in non-tumour tissues (P < 0.001). Moreover, GPX2 expression has statistically significant difference in the tumour histological grade of ESCC (P < 0.001), while there was no statistically significant difference in age, sex, tumour size, tumour location, gross morphology and clinical TNM stages (P > 0.05). Meanwhile, the expression of GPX2 protein was obviously down-regulated within poorly differentiated ESCC. Last, survival analysis revealed that tumour histological grade and clinical TNM stages, both of the clinical pathological parameters of ESCC, were associated with the prognosis of patients with ESCC (respectively, P = 0.009, HR (95 % CI) = 1.885 (1.212 ~ 2.932); P = 0.007, HR (95 % CI) = 2.046 (1.318 ~ 3.177)). More importantly, loss expression of GPX2 protein predicted poor prognosis in patients with ESCC (P < 0.001, HR (95 % CI) = 5.700 (2.337 ~ 13.907)). CONCLUSIONS: Collectively, these results suggested that the expression of GPX2 was significantly up-regulated within ESCC tumour tissues. GPX2 might be an important predictor for the prognosis of ESCC and a potential target for intervention and treatment of ESCC. PMID- 27388202 TI - [Optical coherence tomography angiography (OCT-A) in rats]. AB - PURPOSE: Optical coherence tomography angiography (OCT-A) allows for the non invasive, three-dimensional visualization of retinal and chorioidal vascular structures. In this study, this new imaging modality was evaluated in rats. METHODS: In vivo imaging in Dark Agouti rats was performed using confocal scanning laser ophthalmoscopy (cSLO) and OCT-A (Spectralis prototype, Heidelberg Engineering) after adjusting the length of the reference arm. The OCT-A en-face images were compared to conventional fluorescein angiography cSLO images. The histological examination allowed for correlation of retinal and chorioidal plexus. RESULTS: While the diagnostic device was developed for use in humans, OCT A and cSLO imaging can be applied in rodents after only minor hardware modifications. High-resolution and contrast-enhanced images enable a depth selective visualization of the three retinal plexus and the inner and outer chorioidal vascular networks. In comparison to fluorescein angiography (FA), OCT A is characterized by higher resolution and more accurate three-dimensional localization of vascular structures, particularly in deep layers. A current limitation includes the relatively small area imaged by OCT-A. DISCUSSION: The recently developed OCT-A imaging technology also allows for three-dimensional detection of retinal and chorioidal vascular changes in vivo without dye injection in rodents. OCT may potentially replace invasive FA for specific questions and will be useful in animal models for research of retinal and chorioidal angiogenic processes physiologically and during pharmacological interventions. PMID- 27388203 TI - [Conservative and surgical treatment of convergence excess]. AB - Convergence excess is a common finding especially in pediatric strabismus. A detailed diagnostic approach has to start after full correction of any hyperopia measured in cycloplegia. It includes measurements of manifest and latent deviation at near and distance fixation, near deviation after relaxation of accommodation with addition of +3 dpt, assessment of binocular function with and without +3 dpt as well as the accommodation range. This diagnostic approach is important for the classification into three types of convergence excess, which require different therapeutic approaches: 1) hypo-accommodative convergence excess is treated with permanent bifocal glasses, 2) norm-accommodative patients should be treated with bifocals which can be weaned over years, especially in patients with good stereopsis and 3) non-accommodative convergence excess and patients with large distance deviations need a surgical approach. The most effective operations include those which reduce the muscle torque, e. g. bimedial Faden operations or Y-splitting of the medial rectus muscles. PMID- 27388204 TI - Estimating the incidence of malignant mesothelioma in Vietnam: a pilot descriptive cancer registration study. AB - INTRODUCTION: Global asbestos consumption has shifted toward lower income countries, particularly in the Asian region including Vietnam where asbestos and asbestos-containing products have been imported since the late 1960s. METHODS: This pilot descriptive epidemiological study aimed to provide contemporary estimates of malignant mesothelioma incidence (histological subtype M9050/3; ICD O-3) by gender and age group as recorded across nine cancer registries in Vietnam. RESULTS: We identified 148 incident cases of malignant mesothelioma during 1987-2013. The majority of cases were recorded in the Hanoi region (n = 93) and were aged 55 years or older (n = 96). DISCUSSION: By carefully reviewing existing cancer registry records in Vietnam, we identified a larger number of malignant mesothelioma cases than previously estimated. We recommend the use of cancer registry data in tracking future asbestos-related disease in Vietnam. PMID- 27388205 TI - Change in obsessive beliefs as predictor and mediator of symptom change during treatment of obsessive-compulsive disorder - a process-outcome study. AB - BACKGROUND: Cognitive models of obsessive-compulsive disorder suggest that changes in obsessive beliefs are a key mechanism of treatments for obsessive compulsive disorder. Thus, in the present process-outcome study, we tested whether changes in obsessive beliefs during a primarily cognitive behavioral inpatient treatment predicted treatment outcome and whether these changes mediated symptom changes over the course of treatment. METHODS: Seventy-one consecutively admitted inpatients with obsessive-compulsive disorder were assessed with the Yale-Brown Obsessive-Compulsive Scale and the Obsessive Beliefs Questionnaire at treatment intake, after six weeks of treatment and at discharge, and with the Beck-Depression-Inventory-II at intake and discharge. RESULTS: Changes in obsessive beliefs during the first six weeks of treatment predicted obsessive-compulsive symptoms at discharge when controlling for obsessive compulsive and depressive symptoms at intake in a hierarchical regression analysis. Multilevel mediation analyses showed that reductions in obsessive beliefs partially mediated improvements in obsessive-compulsive symptoms over time. CONCLUSIONS: Our findings indicate that decreasing obsessive beliefs in inpatient cognitive behavioral therapy for obsessive-compulsive disorder might be a promising treatment approach. PMID- 27388206 TI - Interactions of Isonitriles with Metal-Boron Bonds: Insertions, Coupling, Ring Formation, and Liberation of Monovalent Boron. AB - Boryl, borylene, and base-stabilized borylene complexes of manganese and iron undergo a range of different reactions when treated with isonitriles including single, double, and partial isonitrile insertions into metal-boron bonds, ring formation, isonitrile coupling, and the liberation of new monovalent boron species. Two of the resulting cyclic species have also been found to react selectively with anhydrous HCl to form ring-opened products. The diverse isonitrile-promoted reactivity of transition-metal-boron compounds has been explored computationally. PMID- 27388208 TI - A Fine-Tuned Fluorinated MOF Addresses the Needs for Trace CO2 Removal and Air Capture Using Physisorption. AB - The development of functional solid-state materials for carbon capture at low carbon dioxide (CO2) concentrations, namely, from confined spaces (<0.5%) and in particular from air (400 ppm), is of prime importance with respect to energy and environment sustainability. Herein, we report the deliberate construction of a hydrolytically stable fluorinated metal-organic framework (MOF), NbOFFIVE-1-Ni, with the appropriate pore system (size, shape, and functionality), ideal for the effective and energy-efficient removal of trace carbon dioxide. Markedly, the CO2 selective NbOFFIVE-1-Ni exhibits the highest CO2 gravimetric and volumetric uptake (ca. 1.3 mmol/g and 51.4 cm(3) (STP) cm(-3)) for a physical adsorbent at 400 ppm of CO2 and 298 K. Practically, NbOFFIVE-1-Ni offers the complete CO2 desorption at 328 K under vacuum with an associated moderate energy input of 54 kJ/mol, typical for the full CO2 desorption in conventional physical adsorbents but considerably lower than chemical sorbents. Noticeably, the contracted square like channels, affording the close proximity of the fluorine centers, permitted the enhancement of the CO2-framework interactions and subsequently the attainment of an unprecedented CO2 selectivity at very low CO2 concentrations. The precise localization of the adsorbed CO2 at the vicinity of the periodically aligned fluorine centers, promoting the selective adsorption of CO2, is evidenced by the single-crystal X-ray diffraction study on NbOFFIVE-1-Ni hosting CO2 molecules. Cyclic CO2/N2 mixed-gas column breakthrough experiments under dry and humid conditions corroborate the excellent CO2 selectivity under practical carbon capture conditions. Pertinently, the notable hydrolytic stability positions NbOFFIVE-1-Ni as the new benchmark adsorbent for direct air capture and CO2 removal from confined spaces. PMID- 27388207 TI - OptiMal-PK: an internet-based, user-friendly interface for the mathematical-based design of optimized anti-malarial treatment regimens. AB - BACKGROUND: The search for highly effective anti-malarial therapies has gathered pace and recent years have seen a number of promising single and combined therapies reach the late stages of development. A key drug development challenge is the need for early assessment of the clinical utility of new drug leads as it is often unclear for developers whether efforts should be focused on efficacy or metabolic stability/exposure or indeed whether the continuation of iterative QSAR (quantitative structure-activity and relationships) cycles of medicinal chemistry and biological testing will translate to improved clinical efficacy. Pharmacokinetic and pharmacodynamic (PK/PD)-based measurements available from in vitro studies can be used for such clinical predictions. However, these predictions often require bespoke mathematical PK/PD modelling expertise and are normally performed after candidate development and, therefore, not during the pre clinical development phase when such decisions need to be made. METHODS: An internet-based tool has been developed using STELLA((r)) software. The tool simulates multiple differential equations that describe anti-malarial PK/PD relationships where the user can easily input PK/PD parameters. The tool utilizes a simple stop-light system to indicate the efficacy of each combination of parameters. This tool, called OptiMal-PK, additionally allows for the investigation of the effect of drug combinations with known or custom compounds. RESULTS: The results of simulations obtained from OptiMal-PK were compared to a previously published and validated mathematical model on which this tool is based. The tool has also been used to simulate the PK/PD relationship for a number of existing anti-malarial drugs in single or combined treatment. Simulations were predictive of the published clinical parasitological clearance activities for these existing therapies. CONCLUSIONS: OptiMal-PK is designed to be implemented by medicinal chemists and pharmacologists during the pre-clinical anti-malarial drug development phase to explore the impact of different PK/PD parameters upon the predicted clinical activity of any new compound. It can help investigators to identify which pharmacological features of a compound are most important to the clinical performance of a new chemical entity and how partner drugs could potentially improve the activity of existing therapies. PMID- 27388209 TI - The complete genome of the tospovirus Zucchini lethal chlorosis virus. AB - BACKGROUND: Zucchini lethal chlorosis virus (ZLCV) causes significant losses in the production of cucurbits in Brazil. This virus belongs to the genus Tospovirus (family Bunyaviridae) and seems to be exclusively transmitted by Frankliniella zucchini (Thysanoptera). Tospoviruses have a tripartite and single-stranded RNA genome classified as S (Small), M (Medium) and L (Large) RNAS. Although ZLCV was identified as a member of the genus Tospovirus in 1999, its complete genome had not been sequenced until now. FINDINGS: We sequenced the full-length genome of two ZLCV isolates named ZLCV-SP and ZLCV-DF. The phylogenetic analysis showed that ZLCV-SP and ZLCV-DF clustered with the previously reported isolate ZLCV BR09. Their proteins were closely related, except the non-structural protein (NSm), which was highly divergent (approximately 90 % identity). All viral proteins clustered similarly in our phylogenetic analysis, excluding that these ZLCV isolates have originated from reassortment events of different tospovirus species. CONCLUSION: Here we report for the first time the complete genome of two ZLCV isolates that were found in the field infecting zucchini and cucumber. PMID- 27388210 TI - Factors associated with late recurrence after completion of 5-year adjuvant tamoxifen in estrogen receptor positive breast cancer. AB - BACKGROUND: Recent large trials have shown the survival benefits of 10-year use of tamoxifen by reducing late recurrence compared with 5-year therapy in estrogen receptor(ER)-positive breast cancer. We tried to identify clinical factors associated with the late recurrence. METHODS: We reviewed our database of ER positive patients who had received operations between 1996 and 2006 in two institutions. We selected 444 who had completed 5-year tamoxifen and were disease free up to 10 years after the operation. Patients who had received aromatase inhibitors with any regimens were excluded. As a late recurrence group, 139 patients were identified who had completed 5-year tamoxifen, but had recurrence afterwards. Among them, 61 had local/contralateral breast recurrence and 78 had distant metastasis. The median follow-up was 9.7 years. Clinicopathological factors at the time of initial operation, such as age, menopausal status, progesterone receptor expression, HER2 status, tumor grade and Ki-67, were compared between the disease-free group and the late recurrence group. RESULTS: In a univariate analysis, tumor size (>2 cm), lymph node metastasis and high histologic grade were significantly associated with late recurrences (p < 0.05). In a multivariate analysis, only axillary lymph node metastasis was significant (p < 0.001). Late distant metastasis was significantly associated with tumor size and axillary lymph node metastasis (p = 0.038, p < 0.001,respectively). Late local/contralateral breast recurrence was associated with axillary lymph node metastasis (p = 0.042). CONCLUSIONS: Our data showed axillary lymph node metastasis at initial operation was the only risk factor of late recurrence after completion of tamoxifen for 5 years. Our results can be helpful in making decisions to use extended tamoxifen beyond 5 years. PMID- 27388212 TI - Validation study of arm positions for evaluation of global spinal balance in EOS imaging. AB - BACKGROUND: The sagittal vertical axis (SVA) is important in the evaluation of spinal sagittal balance. Although the "fists-on-clavicles" (FOC) position has been widely used in radiographic examinations, it does not define shoulder flexion in detail. Meanwhile, in EOS imaging, the "hands-on-cheeks" (HOC) position is widely used but has not been well investigated. The purpose of this study was to investigate the relative usefulness of FOC and HOC in investigating SVA. MATERIALS AND METHODS: Mean SVA was measured by EOS imaging using standing lateral radiographs of 34 volunteers in four different positions: relaxed (RLX), shoulder flexion at 90 degrees with FOC (FOC90), elbows touching the trunk with FOC (FOCET), and HOC. RESULTS: The mean SVA was 2.0 +/- 2.1 cm in RLX; -1.4 +/- 3.2 cm in FOC90; -0.5 +/- 3.0 cm in FOCET; and -0.2 +/- 2.9 cm in HOC. The negative shift from RLX was significantly greater in FOC90 than in FOCET (-3.4 +/ 2.2 vs -2.5 +/- 2.4 cm; p = 0.0182). The negative shift from RLX in HOC was almost equal to that in FOCET; the difference was 0.3 cm (-2.2 +/- 2.2 vs -2.5 +/ 2.4 cm; p = 0.2560). CONCLUSION: FOC90 showed a negative SVA shift in comparison with FOCET. The difference in the mean SVA between HOC and FOCET was 0.3 cm, a clinically small difference. PMID- 27388211 TI - QTL underlying some agronomic traits in barley detected by SNP markers. AB - BACKGROUND: Increasing the yield of barley (Hordeum vulgare L.) is a main breeding goal in developing barley cultivars. A high density genetic linkage map containing 1894 SNP and 68 SSR markers covering 1375.8 cM was constructed and used for mapping quantitative traits. A late-generation double haploid population (DH) derived from the Huaai 11 * Huadamai 6 cross was used to identify QTLs and QTL * environment interactions for ten traits affecting grain yield including length of main spike (MSL), spikelet number on main spike (SMS), spikelet number per plant (SLP), grain number per plant (GP), grain weight per plant (GWP), grain number per spike (GS), thousand grain weight (TGW), grain weight per spike (GWS), spike density (SPD) and spike number per plant (SP). RESULTS: In single environment analysis using composite interval mapping (CIM), a total of 221 QTLs underlying the ten traits were detected in five consecutive years (2009-2013). The QTLs detected in each year were 50, 48, 41, 41 and 41 for the year 2009 to 2013. The QTLs associated with these traits were generally clustered on chromosome 2H, 4H and 7H. In multi-environment analysis, a total of 111 significant QTLs including 18 for MSL, 16 for SMS, 15 for SPD, 5 for SP, 4 for SLP, 14 for TGW, 5 for GP, 11 for GS, 8 for GWP, and 15 for GWS were detected in the five years. Most QTLs showed significant QTL * environment interactions (QEI), nine QTLs (qIMSL3-1, qIMSL4-1, qIMSL4-2, qIMSL6-1, qISMS7-1, qISPD2-7, qISPD7-1, qITGW3-1 and qIGWS4-3) were detected with minimal QEI effects and stable in different years. Among 111 QTLs,71 (63.40 %) QTLs were detected in both single and multiple environments. CONCLUSIONS: Three main QTL cluster regions associated with the 10 agronomic traits on chromosome 2H, 4H and 7H were detected. The QTLs for SMS, SLP, GP and GWP were located in the region near Vrs1 on chromosome 2H. The QTLs underlying SMS, SPD and SLP were clustered on chromosome 4H. On the terminal of chromosome 7H, there was a QTL cluster associated with TGW, SPD, GWP and GWS. The information will be useful for marker assisted selection (MAS) in barley breeding. PMID- 27388213 TI - Hamstring graft tibial insertion preservation versus detachment in anterior cruciate ligament reconstruction: a prospective randomized comparative study. AB - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction with hamstring graft (HG) is a commonly performed procedure. Despite the type of reconstruction chosen, the detached HG undergoes a remodeling process known as ligamentization. In order to shorten the ligamentization process, the maintenance of HG tibial insertion, aimed to spare the tendons vascular supply, has been postulated. The aim of this paper is to report the results of a prospective randomized study comparing clinical and MRI results between two different ACL reconstructive procedures with and without HG tibial insertion preservation. METHODS: Forty patients (mean age 27.5 +/- 9.5 years) were enrolled and randomly divided into two groups. The study group underwent an ACL reconstruction using a distally inserted HG, while the control group underwent a technique encompassing HG tibial detachment. Subjective and objective IKDC score was administered preoperatively and at 3-, 6-, 12- and 24-month follow-up. Graft morphology was assessed through MRI evaluation performed at 6-month follow-up. RESULTS: Clinical results were excellent in both groups. Regarding MRI results, a better intra-articular graft morphology was observed in the study group (Tau = 0.313, p = 0.024). No differences in graft integration were noticed. CONCLUSION: The main finding of this preliminary study is that preservation of the hamstring tibial insertion seems to enhance graft ligamentization with improved morphology of the intra articular portion of the graft compared to a detachment of the hamstring tendons from the tibial side. Further well-designed studies with higher number of patients as well as more serial MRI evaluations are required to validate these preliminary findings. PMID- 27388214 TI - The contribution of vascular and extra-vascular water pathways to drought-induced decline of leaf hydraulic conductance. AB - Drought stress can impair leaf hydraulic conductance (Kleaf), but the relative contribution of changes in the efficiency of the vein xylem water pathway and in the mesophyll route outside the xylem in driving the decline of Kleaf is still debated. We report direct measurements of dehydration-induced changes in the hydraulic resistance (R=1/K) of whole leaf (Rleaf), as well as of the leaf xylem (Rx) and extra-vascular pathways (Rox) in four Angiosperm species. Rleaf, Rx, and Rox were measured using the vacuum chamber method (VCM). Rleaf values during progressive leaf dehydration were also validated with measurements performed using the rehydration kinetic method (RKM). We analysed correlations between changes in Rx or Rox and Rleaf, as well as between morpho-anatomical traits (including dehydration-induced leaf shrinkage), vulnerability to embolism, and leaf water relation parameters. Measurements revealed that the relative contribution of vascular and extra-vascular hydraulic properties in driving Kleaf decline during dehydration is species-specific. Whilst in two study species the progressive impairment of both vascular and extra-vascular pathways contributed to leaf hydraulic vulnerability, in the other two species the vascular pathway remained substantially unaltered during leaf dehydration, and Kleaf decline was apparently caused only by changes in the hydraulic properties of the extra vascular compartment. PMID- 27388215 TI - Chemical Sniffing Instrumentation for Security Applications. AB - Border control for homeland security faces major challenges worldwide due to chemical threats from national and/or international terrorism as well as organized crime. A wide range of technologies and systems with threat detection and monitoring capabilities has emerged to identify the chemical footprint associated with these illegal activities. This review paper investigates artificial sniffing technologies used as chemical sensors for point-of-use chemical analysis, especially during border security applications. This article presents an overview of (a) the existing available technologies reported in the scientific literature for threat screening, (b) commercially available, portable (hand-held and stand-off) chemical detection systems, and (c) their underlying functional and operational principles. Emphasis is given to technologies that have been developed for in-field security operations, but laboratory developed techniques are also summarized as emerging technologies. The chemical analytes of interest in this review are (a) volatile organic compounds (VOCs) associated with security applications (e.g., illegal, hazardous, and terrorist events), (b) chemical "signatures" associated with human presence, and PMID- 27388216 TI - DNA Damage and the Activation of the p53 Pathway Mediate Alterations in Metabolic and Secretory Functions of Adipocytes. AB - Activation of the p53 pathway in adipose tissue contributes to insulin resistance associated with obesity. However, the mechanisms of p53 activation and the effect on adipocyte functions are still elusive. Here we found a higher level of DNA oxidation and a reduction in telomere length in adipose tissue of mice fed a high fat diet and an increase in DNA damage and activation of the p53 pathway in adipocytes. Interestingly, hallmarks of chronic DNA damage are visible at the onset of obesity. Furthermore, injection of lean mice with doxorubicin, a DNA damage-inducing drug, increased the expression of chemokines in adipose tissue and promoted its infiltration by proinflammatory macrophages and neutrophils together with adipocyte insulin resistance. In vitro, DNA damage in adipocytes increased the expression of chemokines and triggered the production of chemotactic factors for macrophages and neutrophils. Insulin signaling and effect on glucose uptake and Glut4 translocation were decreased, and lipolysis was increased. These events were prevented by p53 inhibition, whereas its activation by nutlin-3 reproduced the DNA damage-induced adverse effects. This study reveals that DNA damage in obese adipocytes could trigger p53-dependent signals involved in alteration of adipocyte metabolism and secretory function leading to adipose tissue inflammation, adipocyte dysfunction, and insulin resistance. PMID- 27388217 TI - Islet Pericytes Are Required for beta-Cell Maturity. AB - beta-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting beta-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to beta-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin-based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression. Additionally, isolated islets displayed impaired glucose-stimulated insulin secretion, accompanied by a reduced expression of genes associated with beta-cell function. Importantly, reduced levels of the transcription factors MafA and Pdx1 point to beta-cell dedifferentiation in the absence of pericytes. Ex vivo depletion of pericytes in isolated islets resulted in a similar impairment of gene expression, implicating their direct, blood flow-independent role in maintaining beta-cell maturity. To conclude, our findings suggest that pericytes are pivotal components of the islet niche, which are required for beta-cell maturity and functionality. Abnormalities of islet pericytes, as implicated in type 2 diabetes, may therefore contribute to beta-cell dysfunction and disease progression. PMID- 27388218 TI - Gene Expression and DNA Methylation of PPARGC1A in Muscle and Adipose Tissue From Adult Offspring of Women With Diabetes in Pregnancy. AB - Prenatal exposure to maternal hyperglycemia is associated with an increased risk of later adverse metabolic health. Changes in the regulation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) in skeletal muscle and subcutaneous adipose tissue (SAT) is suggested to play a role in the developmental programming of dysmetabolism based on studies of human subjects exposed to an abnormal intrauterine environment (e.g., individuals with a low birth weight). We studied 206 adult offspring of women with gestational diabetes mellitus (O-GDM) or type 1 diabetes (O-T1D) and of women from the background population (O-BP) using a clinical examination, oral glucose tolerance test, and gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT. Plasma glucose was significantly higher for both O-GDM and O-T1D compared with O BP (P < 0.05). PPARGC1A gene expression in muscle was lower in O-GDM compared with O-BP (P = 0.0003), whereas no differences were found between O-T1D and O-BP in either tissue. PPARGC1A DNA methylation percentages in muscle and SAT were similar among all groups. Decreased PPARGC1A gene expression in muscle has previously been associated with abnormal insulin function and may thus contribute to the increased risk of metabolic disease in O-GDM. The unaltered PPARGC1A gene expression in muscle of O-T1D suggests that factors other than intrauterine hyperglycemia may contribute to the decreased PPARGC1A expression in O-GDM. PMID- 27388219 TI - NMDA Receptors as Potential Therapeutic Targets in Diabetic Nephropathy: Increased Renal NMDA Receptor Subunit Expression in Akita Mice and Reduced Nephropathy Following Sustained Treatment With Memantine or MK-801. AB - N-methyl-d-aspartate (NMDA) receptors are expressed throughout the kidney, and the abundance of these receptors and some of their endogenous agonists are increased in diabetes. Moreover, sustained activation of podocyte NMDA receptors induces Ca(2+) influx, oxidative stress, loss of slit diaphragm proteins, and apoptosis. We observed that NMDA receptor subunits and their transcripts are increased in podocytes and mesangial cells cultured in elevated glucose compared with controls. A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice. Sustained continuous treatment with the strong NMDA receptor antagonist dizocilpine (MK-801) for 28 days starting at 8 weeks of age reduced 24-h albumin excretion and mesangial matrix expansion and improved glomerular ultrastructure in Akita mice. MK-801 did not alleviate reduced Akita mouse body weight and had no effect on kidney histology or ultrastructure in DBA/2J controls. The structurally dissimilar NMDA antagonist memantine also reduced diabetic nephropathy, although it was less effective than MK-801. Inhibition of NMDA receptors may represent a valid therapeutic approach to reduce renal complications of diabetes, and it is possible to develop well-tolerated agents with minimal central nervous system effects. Two such agents, memantine and dextromethorphan, are already in widespread clinical use. PMID- 27388220 TI - From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety. AB - INTRODUCTION: Pharmacologic vitreolysis is a strategy used to treat anomalous posterior vitreous detachment, by weakening vitreoretinal adhesion with an intravitreal drug. Pharmacologic vitreolysis facilitates surgery, and abnormalities of the vitreoretinal interface including vitreomacular traction (VMT) and early stage macular hole (MH) could be resolved. Ocriplasmin is a recombinant protease, active against fibronectin and laminin, which are important components of the vitreoretinal interface. Ocriplasmin has been approved for symptomatic treatment of VMT and MH with visible traction, and it functions by dissolving the proteins that link the vitreous to the macula, thereby creating a complete posterior vitreous detachment (PVD). AREAS COVERED: This paper reviews the current knowledge and status of investigations regarding the use of ocriplasmin for pharmacologic vitreolysis and its safety. EXPERT OPINION: Ocriplasmin is a non-specific enzyme; therefore, it dissolves vitreal proteins as well as possibly proteins associated with visual function in the retina, choroid, and lens. Ocular adverse events (OAEs) of ocriplasmin include transient visual loss, intraocular inflammation, vitreous floaters, lens opacification, zonular instability of the lens, and intraocular hemorrhage. The prevalence of the OAEs is very low; however, on rare occasions, they can result in widespread retinal dysfunction. Research into the acute and long-term safety of ocriplasmin is required. PMID- 27388221 TI - Development and validation of a decision aid for choosing among antithrombotic agents for atrial fibrillation. AB - BACKGROUND: Multiple antithrombotic agents are available for stroke prevention in atrial fibrillation (AF). A decision aid can assist patients in making informed decisions that best serves their needs. OBJECTIVE: To validate a decision aid to assist patients in choosing between antithrombotic agents (antiplatelets, warfarin, direct-acting oral anticoagulants (DOACs)) for AF. METHODS: Patients (60years or older) were recruited for this prospective study. The decision aid presented descriptions related to AF, then charts portraying important outcomes for comparisons between 1) no treatment, aspirin and anticoagulants, 2) warfarin versus DOACs, and 3) DOAC versus DOAC. The primary outcome was confidence in making treatment decisions. The secondary outcomes included change in knowledge scores, ratings of clarity, helpfulness and comprehensiveness. RESULTS: Eighty one patients (mean age 75.2 [SD 7.5], 77% taking an anticoagulant) participated. After using the decision aid, mean decisional conflict score was low at 7.2 [SD 10.8] on a scale from 1 to 100. Mean knowledge score (total possible 10) improved from 7.4 [SD 1.7] to 9.3 [SD 1.0] (p<0.001). The mean helpfulness score in making a treatment choice was high at 6.2 [SD 0.9] on a scale from 1 to 7. No participant found the decision aid difficult to understand. Information in the decision aid was rated as good or excellent in terms of clarity and comprehensiveness. CONCLUSIONS: Our decision aid addresses a key medication safety gap - assisting patients to participate in shared decisions about anticoagulation. Future research is required to evaluate how decision aids influence actual choices and clinical outcomes. PMID- 27388222 TI - Inside out the thrombus: Defining the role of von Willebrand factor. PMID- 27388223 TI - Dendrimer-based magnetic iron oxide nanoparticles: their synthesis and biomedical applications. AB - Magnetic iron oxide nanoparticles (MIO NPs) bearing different appropriate surface modifications can be prepared using diverse physical and chemical methods. As an ideal macromolecule, dendrimers have attracted considerable attention because of their unique properties, including their three 3D architecture, monodispersity, highly branched macromolecular characteristics, and tunable terminal functionalities. These properties make dendrimers a powerful nanoplatform for the creation of functional organic and/or inorganic hybrid NPs, in particular dendrimer-based MIO NPs. Here, we report on recent advances in the preparation of dendrimer-based MIO NPs for different biomedical applications, such as magnetic resonance (MR) imaging, drug and gene delivery, and protein immobilization. PMID- 27388224 TI - Improving healthcare for Aboriginal Australians through effective engagement between community and health services. AB - BACKGROUND: Effectively addressing health disparities between Aboriginal and non Aboriginal Australians is long overdue. Health services engaging Aboriginal communities in designing and delivering healthcare is one way to tackle the issue. This paper presents findings from evaluating a unique strategy of community engagement between local Aboriginal people and health providers across five districts in Perth, Western Australia. Local Aboriginal community members formed District Aboriginal Health Action Groups (DAHAGs) to collaborate with health providers in designing culturally-responsive healthcare. The purpose of the strategy was to improve local health service delivery for Aboriginal Australians. METHODS: The evaluation aimed to identify whether the Aboriginal community considered the community engagement strategy effective in identifying their health service needs, translating them to action by local health services and increasing their trust in these health services. Participants were recruited using purposive sampling. Qualitative data was collected from Aboriginal participants and health service providers using semi-structured interviews or yarning circles that were recorded, transcribed and independently analysed by two senior non-Aboriginal researchers. Responses were coded for key themes, further analysed for similarities and differences between districts and cross-checked by the senior lead Aboriginal researcher to avoid bias and establish reliability in interpreting the data. Three ethics committees approved conducting the evaluation. RESULTS: Findings from 60 participants suggested the engagement process was effective: it was driven and owned by the Aboriginal community, captured a broad range of views and increased Aboriginal community participation in decisions about their healthcare. It built community capacity through regular community forums and established DAHAGs comprising local Aboriginal community members and health service representatives who met quarterly and were supported by the Aboriginal Health Team at the local Population Health Unit. Participants reported health services improved in community and hospital settings, leading to increased access and trust in local health services. CONCLUSION: The evaluation concluded that this process of actively engaging the Aboriginal community in decisions about their health care was a key element in improving local health services, increasing Aboriginal people's trust and access to care. PMID- 27388225 TI - Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography-tandem mass spectrometry. AB - We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography-tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats. PMID- 27388226 TI - Effect of silica coating on the bond strength of milled pure titanium to dental porcelain. AB - The creation of a high bond strength between machined computer-manufactured pure titanium and porcelain remains problematic, and the effects of a silica coating on the bond strength of milled pure titanium bonded to dental porcelain require further investigation. The objective of this study was to evaluate the bond strength of machined pure titanium, with an intermediate coating of silica, to dental porcelain. In this work, 24 specimens of milled pure titanium were prepared and randomly divided into test and control groups, in which the test group was coated with silica using the sol-gel dipping technique. The metal ceramic bond strength was evaluated, according to ISO 9693 standards, using the three-point bending test, and scanning electron microscopy and energy-dispersive spectroscopy were used to study the microstructure and elemental composition of the specimens. The bonding strength of the silica-coated group was significantly higher than that of the control group, and more residual porcelain on the metal surface could be observed in the silica-coated group. Therefore, the application of a silica intermediate coating produced using the sol-gel method could significantly improve the bond strength between machined pure titanium and porcelain. PMID- 27388227 TI - Culture- and Immigration-Related Stress Faced by Chinese American Families with a Patient Having Schizophrenia. AB - The impact of culture and immigration on the experience of Chinese American families with a member having schizophrenia is explored within the frameworks of family systems and stress and coping. This qualitative study was conducted within an intervention study of family psychoeducation using therapists' session notes from 103 family sessions and 13 relatives' group sessions from nine patients and 19 relatives. The high stigma attached to mental illness leading to social isolation, and families' devotion to caregiving exacerbated caregiver burden. Taboo against discussing dating and sexuality and the consideration of arranged marriages caused unique stress. The insecurity as immigrants and shortage of bilingual services were related to greater enmeshment within these families. Implications on research methodology and practice are discussed. PMID- 27388228 TI - Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis. AB - CONTEXT: Association between inherited variants and the risks of sepsis is controversial. OBJECTIVE: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10. MATERIALS AND METHODS: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls. RESULTS: Subjects with IL-10 -1082 AA genotypes and IL-6 -174 CC genotype had a higher risk of sepsis and increased mRNA levels. CONCLUSION: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis. PMID- 27388229 TI - Comparison between objective and subjective benign paroxysmal positional vertigo: clinical features and outcomes. AB - CONCLUSIONS: Objective benign paroxysmal positional vertigo (O-BPPV) and subjective BPPV (S-BPPV) have similar demographic and clinical features. Canalith repositioning manoeuvres (CRMs) can be an effective treatment for patients with S BPPV, and a diagnosis of positional nystagmus is not essential for considering CRMs. This study supports the use of CRMs as the primary treatment for S-BPPV. OBJECTIVE: To examine differences in demographic and clinical features, as well as treatment outcomes, between O-BPPV and S-BPPV. METHODS: The medical records of 134 patients with BPPV were reviewed for demographic characteristics, past medical history, associated symptoms, response to CRMs, interval between symptom onset and the first medical visit, and recurrence rate. The O-BPPV group (n = 101) comprised patients who experienced vertigo and accompanying autonomic symptoms, and showed typical nystagmus. The S-BPPV group (n = 33) comprised patients who, when subjected to a provoking manoeuvre, showed all of the classic BPPV symptoms but did not show nystagmus. All patients had at least 3 years of follow-up. RESULTS: The demographics (age and sex ratio), past medical history, and associated symptoms were not significantly different between the two groups. Posterior semi-circular canal BPPV appeared more than twice as often as horizontal semi-circular canal BPPV in patients with S-BPPV. However, both canals were affected to a similar proportion in patients with O-BPPV, and the difference was marginally significant (p = 0.073). Overall improvement was better in O-BPPV than in S-BPPV; however, there was no significant difference. The total numbers of manoeuvres for recovery and the interval between symptom onset and the first medical visit also did not show any significant inter-group differences. During a 3-year follow-up, the recurrence rate was 13.8% for O-BPPV and 21.2% for S-BPPV. PMID- 27388230 TI - Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus. AB - OBJECTIVES: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology. MATERIALS AND METHODS: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age). RESULTS: Aqueduct stroke volume was higher in INPH than healthy (148+/-95 vs 90+/ 50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays. CONCLUSIONS: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear. PMID- 27388231 TI - Two-Dimensional Atomic-Layered Alloy Junctions for High-Performance Wearable Chemical Sensor. AB - We first report that two-dimensional (2D) metal (NbSe2)-semiconductor (WSe2) based flexible, wearable, and launderable gas sensors can be prepared through simple one-step chemical vapor deposition of prepatterned WO3 and Nb2O5. Compared to a control device with a Au/WSe2 junction, gas-sensing performance of the 2D NbSe2/WSe2 device was significantly enhanced, which might have resulted from the formation of a NbxW1-xSe2 transition alloy junction lowering the Schottky barrier height. This would make it easier to collect charges of channels induced by molecule adsorption, improving gas response characteristics toward chemical species including NO2 and NH3. 2D NbSe2/WSe2 devices on a flexible substrate provide gas-sensing properties with excellent durability under harsh bending. Furthermore, the device stitched on a T-shirt still performed well even after conventional cleaning with a laundry machine, enabling wearable and launderable chemical sensors. These results could pave a road toward futuristic gas-sensing platforms based on only 2D materials. PMID- 27388232 TI - Pretreatment Insulin Levels as a Prognostic Factor for Breast Cancer Progression. AB - BACKGROUND: Based on the hypothesis that impaired glucose metabolism might be associated with survival outcomes independently of overt diabetes, we sought to investigate the prognostic value of routinely used glycemic parameters in a prospective study of breast cancer (BC) patients. PATIENTS AND METHODS: Fasting blood glucose, insulin and HbA1c levels, and insulin resistance (assessed by the Homeostasis Model Assessment [HOMA] index) at diagnosis were evaluated in 286 nondiabetic BC patients (249 with primary cancer, 37 with metastatic) with respect to those parameters' possible associations with clinicopathological features and survival outcomes. As a control group, 143 healthy women matched in a 2:1 ratio for age, blood lipid levels, and body mass index were also investigated. RESULTS: Fasting blood glucose level (mean +/- SD: 99 +/- 26 vs. 85 +/- 15 mg/dL), insulin level (median: 10.0 vs. 6.8 MUIU/mL), and HOMA index (median: 2.2 vs. 1.4), but not HbA1c level, were significantly elevated in BC patients compared with control subjects. Receiver operating characteristics analysis showed comparable areas for blood glucose and insulin levels, and HOMA index (ranging from 0.668 to 0.671). Using a cutoff level of 13 MUIU/mL, insulin had the best specificity (92%) and sensitivity (41%), was significantly associated with disease stage, and acted as a negative prognostic marker of progression-free survival (hazard ratio: 2.17; 95% confidence interval: 1.13 4.20) independently of menopausal status, disease stage, hormone receptor status, and human epidermal growth factor receptor 2 and Ki67 expression. CONCLUSION: These results suggest that insulin determination might provide prognostic information in BC and support the hypothesis that lifestyle and/or pharmacological interventions targeting glucose metabolism could be considered to improve survival outcome of selected BC patients. IMPLICATIONS FOR PRACTICE: Pretreatment insulin levels may represent a biomarker of adverse prognosis in nondiabetic women with breast cancer, independently of other well-established prognostic factors (i.e., stage, hormone receptors, HER2/neu, and Ki67). This finding has important implications, because it provides the rationale for lifestyle or insulin-targeting pharmacologic interventions as a means of improving breast cancer outcomes not only in early stages, but also in advanced stage breast cancer patients with aggressive tumor phenotypes (HER2-negative hormone-resistant, or triple-negative breast cancer), in which treatments are still challenging. The possibility of using insulin as a biomarker to guide insulin-targeted interventions also should be taken into account. PMID- 27388233 TI - Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer. AB - : A firmer understanding of the genomic landscape of lung cancer has recently led to targeted, therapeutic advances in non-small cell lung cancer. Historically, the reference standard for the diagnosis and genetic interrogation for advanced stage patients has been tissue acquisition via computed tomography-guided core or fine needle aspiration biopsy. However, this process can frequently put the patient at risk and remains complicated by sample availability and tumor heterogeneity. In addition, the time required to complete the diagnostic assays can negatively affect clinical care. Technological advances in recent years have led to the development of blood-based diagnostics or "liquid biopsies" with great potential to quickly diagnose and genotype lung cancer using a minimally invasive technique. Recent studies have suggested that molecular alterations identified in cell-free DNA (cfDNA) or circulating tumor DNA can serve as an accurate molecular proxy of tumor biology and reliably predict the response to tyrosine kinase therapy. In addition, several trials have demonstrated the high accuracy of microRNA (miRNA) platforms in discerning cancerous versus benign nodules in high risk, screened patients. Despite the promise of these platforms, issues remain, including varying sensitivities and specificities between competing platforms and a lack of standardization of techniques and downstream processing. In the present report, the clinical applications of liquid biopsy technologies, including circulating tumor cells, proteomics, miRNA, and cfDNA for NSCLC, are reviewed and insight is provided into the diagnostic and therapeutic implications and challenges of these platforms. IMPLICATIONS FOR PRACTICE: Although tumor biopsies remain the reference standard for the diagnosis and genotyping of non-small cell lung cancer, they remain fraught with logistical complexities that can delay treatment decisions and affect clinical care. Liquid diagnostic platforms, including cell-free DNA, proteomic signatures, RNA (mRNA and microRNA), and circulating tumor cells, have the potential to overcome many of these barriers, including rapid and accurate identification of de novo and resistant genetic alterations, real-time monitoring of treatment responses, prognosis of outcomes, and identification of minimal residual disease. The present report provides insights into new liquid diagnostic platforms in non-small cell lung cancer and discusses the promise and challenges of their current and future clinical use. PMID- 27388234 TI - Cardiogenic Shock and Respiratory Failure in a Patient With Metastatic Melanoma Receiving Trametinib Therapy. PMID- 27388235 TI - Single and mixture effects of aquatic micropollutants studied in precision-cut liver slices of Atlantic cod (Gadus morhua). AB - The low concentrations of most contaminants in the aquatic environment individually may not affect the normal function of the organisms on their own. However, when combined, complex mixtures may provoke unexpected effects even at low amounts. Selected aquatic micropollutants such as chlorpyrifos, bis-(2 ethylhexyl)-phthalate (DEHP), perfluorooctanoic acid (PFOA) and 17alpha ethinylestradiol (EE2) were tested singly and in mixtures at nM to MUM concentrations using precision-cut liver slices (PCLS) of Atlantic cod (Gadus morhua). Fish liver is a target organ for contaminants due to its crucial role in detoxification processes. In order to understand the effects on distinct key liver metabolic pathways, transcription levels of various genes were measured, including cyp1a1 and cyp3a, involved in the metabolism of organic compounds, including toxic ones, and the catabolism of bile acids and steroid hormones; cyp7a1, fabp and hmg-CoA, involved in lipid and cholesterol homeostasis; cyp24a1, involved in vitamin D metabolism; and vtg, a key gene in xenoestrogenic response. Only EE2 had significant effects on gene expression in cod liver slices when exposed singly at the concentrations tested. However, when exposed in combinations, effects not detected in single exposure conditions arose, suggesting complex interactions between studied pollutants that could not be predicted from the results of individual exposure scenarios. Thus, the present work highlights the importance of assessing mixtures when describing the toxic effects of micropollutants to fish liver metabolism. PMID- 27388236 TI - The Humanistic, Societal, and Pharmaco-economic Burden of Angioedema. AB - Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disorder characterized by intermittent and unpredictable episodes of swelling which cause disfigurement, disability, pain, or, in case of laryngeal swelling, risk of death. Historical factors, including the intermittent nature of the disorder, the lack of awareness of this ultra-rare condition amongst medical personnel, lack of specialist centers, and limited treatment options have contributed to under-diagnosis and under-treatment of the condition. Incorrect treatment of attacks has been common, even when medical help is sought. This has lead to reduced health-seeking behavior and alternative coping strategies, sometimes even denial, in many families, while a minority of HAE-affected patients have become serial emergency room attenders with chronic pain and ongoing requirement for opiate-based painkillers. Both strategies have incurred not only physical but also psychological and economic consequences.In the last 10 years, new and effective acute therapies have been made available, some of which have also provided short-term and long-term prophylaxis options, together with a better understanding of older prophylactic drugs. Improved awareness of HAE amongst the general public, family members, and physicians has reduced the long delay in diagnosis and increased the number of patients receiving effective and up-to-date therapies to improve the physical impact of the disorder.Data on the impact of treatment on the psychological outcomes is scarce, but the limited information available suggests that access to specialist advice and treatment leads to psychological as well as physical improvement.HAE also has profound effects on individual and family economic output, directly via absenteeism from school or work and indirectly via lost opportunities. Economic improvements associated with better treatments are offset by the high cost of new acute treatments, resulting in difficult pharmaco-economic calculations. Worldwide, cost considerations present potentially insurmountable barriers to treatment for many patients, depending on the healthcare system in the individual country. PMID- 27388237 TI - Do views on psychosocial needs of children and adolescents differ among professionals depending on their organisational affiliation? A qualitative study. AB - Unit managers and employees in schools, social services, and child and adolescent mental health services (CAMHS) were asked to describe their views on children's and adolescents' psychosocial needs when collaboration was required. A descriptive case study design was employed and data were gathered from 23 professionals in six focus groups. The data were analysed by the use of an inductive content approach. Disparities were identified that were interpreted as different approaches to children's needs, which we designated individual (CAMHS), contextual (social services), and educational (schools) approaches. These were perceived as emerging from the professional representations of children's needs that were created within each working group. The organisational affiliation seemed however to have a stronger influence than professional education, regarding the view of children's needs. We suggest that it would be an advantage for professionals to be able to participate in dialogue groups to discuss the meaning of their organisational and professional affiliations, and how this affects their views. Rather than formal knowledge, such dialogues should contain more essential knowledge related to the professionals' approaches to children's needs and to the diversities in the way they think and work in a "give-and-take" process. This might influence their way of thinking and working with children and adolescents, and strengthen their understanding of each other's work. PMID- 27388238 TI - Chondrocytes Derived From Mesenchymal Stromal Cells and Induced Pluripotent Cells of Patients With Familial Osteochondritis Dissecans Exhibit an Endoplasmic Reticulum Stress Response and Defective Matrix Assembly. AB - : Familial osteochondritis dissecans (FOCD) is an inherited skeletal defect characterized by the development of large cartilage lesions in multiple joints, short stature, and early onset of severe osteoarthritis. It is associated with a heterozygous mutation in the ACAN gene, resulting in a Val-Met replacement in the C-type lectin domain of aggrecan. To understand the cellular pathogenesis of this condition, we studied the chondrogenic differentiation of patient bone marrow mesenchymal stromal cells (BM-MSCs). We also looked at cartilage derived from induced pluripotent stem cells (iPSCs) generated from patient fibroblasts. Our results revealed several characteristics of the differentiated chondrocytes that help to explain the disease phenotype and susceptibility to cartilage injury. First, patient chondrogenic pellets had poor structural integrity but were rich in glycosaminoglycan. Second, it was evident that large amounts of aggrecan accumulated within the endoplasmic reticulum of chondrocytes differentiated from both BM-MSCs and iPSCs. In turn, there was a marked absence of aggrecan in the extracellular matrix. Third, it was evident that matrix synthesis and assembly were globally dysregulated. These results highlight some of the abnormal aspects of chondrogenesis in these patient cells and help to explain the underlying cellular pathology. The results suggest that FOCD is a chondrocyte aggrecanosis with associated matrix dysregulation. The work provides a new in vitro model of osteoarthritis and cartilage degeneration based on the use of iPSCs and highlights how insights into disease phenotype and pathogenesis can be uncovered by studying differentiation of patient stem cells. SIGNIFICANCE: The isolation and study of patient stem cells and the development of methods for the generation of iPSCs have opened up exciting opportunities in understanding causes and exploring new treatments for major diseases. This technology was used to unravel the cellular phenotype in a severe form of inherited osteoarthritis, termed familial osteochondritis dissecans. The phenotypic abnormalities that give rise to cartilage lesions in these patients were able to be described via the generation of chondrocytes from bone marrow-derived mesenchymal stromal cells and iPSCs, illustrating the extraordinary value of these approaches in disease modeling. PMID- 27388239 TI - Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor beta/SMAD2 Pathway During Wound Healing. AB - : : Excessive scar formation caused by myofibroblast aggregations is of great clinical importance during skin wound healing. Studies have shown that mesenchymal stem cells (MSCs) can promote skin regeneration, but whether MSCs contribute to scar formation remains undefined. We found that umbilical cord derived MSCs (uMSCs) reduced scar formation and myofibroblast accumulation in a skin-defect mouse model. We found that these functions were mainly dependent on uMSC-derived exosomes (uMSC-Exos) and especially exosomal microRNAs. Through high throughput RNA sequencing and functional analysis, we demonstrated that a group of uMSC-Exos enriched in specific microRNAs (miR-21, -23a, -125b, and -145) played key roles in suppressing myofibroblast formation by inhibiting the transforming growth factor-beta2/SMAD2 pathway. Finally, using the strategy we established to block miRNAs inside the exosomes, we showed that these specific exosomal miRNAs were essential for the myofibroblast-suppressing and anti scarring functions of uMSCs both in vitro and in vivo. Our study revealed a novel role of exosomal miRNAs in uMSC-mediated therapy, suggesting that the clinical application of uMSC-derived exosomes might represent a strategy to prevent scar formation during wound healing. SIGNIFICANCE: Exosomes have been identified as a new type of major paracrine factor released by umbilical cord-derived mesenchymal stem cells (uMSCs). They have been reported to be an important mediator of cell to-cell communication. However, it is still unclear precisely which molecule or group of molecules carried within MSC-derived exosomes can mediate myofibroblast functions, especially in the process of wound repair. The present study explored the functional roles of uMSC-exosomal microRNAs in the process of myofibroblast formation, which can cause excessive scarring. This is an unreported function of uMSC exosomes. Also, for the first time, the uMSC-exosomal microRNAs were examined by high-throughput sequencing, with a group of specific microRNAs (miR 21, miR-23a, miR-125b, and miR-145) found to play key roles in suppressing myofibroblast formation by inhibiting excess alpha-smooth muscle actin and collagen deposition associated with activity of the transforming growth factor beta/SMAD2 signaling pathway. PMID- 27388240 TI - PTEN Promotes Dopaminergic Neuronal Differentiation Through Regulation of ERK Dependent Inhibition of S6K Signaling in Human Neural Stem Cells. AB - : : Phosphatase and tension homolog (PTEN) is a widely known negative regulator of insulin/phosphatidylinositol 3-kinase (PI3K) signaling. The PI3K/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) and Ras-extracellular signal-regulated kinase (Ras-ERK) signaling pathways are the chief mechanisms controlling the survival, proliferation, and differentiation of neural stem cells (NSCs). However, the roles of PTEN in Akt/mTOR and ERK signaling during proliferation and neuronal differentiation of human NSCs (hNSCs) are poorly understood. Treatment of proliferating hNSCs with a specific inhibitor of PTEN or overexpression of the PTEN inactive mutant G129E resulted in an increase in the expression levels of Ki67, p-S6 kinase (p-S6K), and p-ERK without affecting p-Akt expression during proliferation of hNSCs. Therefore, we focused on the regulatory effect of PTEN in S6K and ERK signaling during dopaminergic neuronal differentiation of hNSCs. Overexpression of PTEN during neuronal differentiation of hNSCs caused an increase in p-S6K expression and a decrease in p-ERK expression. Conversely, inhibition of PTEN increased p-ERK expression and decreased p-S6K expression. Inhibition of ERK by a specific chemical inhibitor, U0126, promoted neuronal generation, especially of tyrosine hydroxylase-positive neurons. p-S6K expression increased in a time-dependent manner during differentiation, and this effect was enhanced by U0126. These results indicated that PTEN promoted neuronal differentiation by inhibition of ERK signaling, which in turn induced activation of S6K. Our data suggest that ERK pathways participate in crosstalk with S6K through PTEN signaling during neuronal differentiation of hNSCs. These results represent a novel pathway by which PTEN may modulate the interplay between ERK and S6K signaling, leading to increased neuronal differentiation in hNSCs. SIGNIFICANCE: This article adds to the body of knowledge about the mechanism of extracellular signal-regulated kinase (ERK)-mediated differentiation by describing the molecular function of phosphatase and tension homolog (PTEN) during the neuronal differentiation of human neural stem cells (hNSCs). Previous studies showed that S6K signaling promoted neuronal differentiation in hNSCs via the phosphatidylinositol 3-kinase Akt-mammalian target of rapamycin signaling pathway. A further series of studies investigated whether this S6 kinase-induced differentiation in hNSCs involves regulation of ERK signaling by PTEN. The current study identified a novel mechanism by which PTEN regulates neuronal differentiation in hNSCs, suggesting that activating PTEN function promotes dopaminergic neuronal differentiation and providing an important resource for future studies of PTEN function. PMID- 27388241 TI - Bone Regeneration Using the Freshly Isolated Autologous Stromal Vascular Fraction of Adipose Tissue in Combination With Calcium Phosphate Ceramics. AB - : : In patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement, bone substitutes are currently evaluated as alternatives for autologous bone. However, bone substitutes have only osteoconductive properties and lack osteoinductive potential. Therefore, this phase I study evaluated the potential additive effect on bone regeneration by the addition of freshly isolated, autologous but heterologous stromal vascular fraction (SVF), which is highly enriched with adipose stromal/stem cells when compared with native adipose tissue. From 10 patients, SVF was procured using automatic processing, seeded on either beta-tricalcium phosphate (n = 5) or biphasic calcium phosphate carriers (n = 5), and used for MSFE in a one-step surgical procedure. Primary objectives were feasibility and safety. The secondary objective was efficacy, evaluated by using biopsies of the augmented area taken 6 months postoperatively, concomitant with dental implant placement. Biopsies were assessed for bone, graft, and osteoid volumes. No adverse effects were reported during the procedure or follow up (>=3 years). Bone and osteoid percentages were higher in study biopsies (SVF supplemented) than in control biopsies (ceramic only on contralateral side), in particular in beta-tricalcium phosphate-treated patients. Paired analysis on the six bilaterally treated patients revealed markedly higher bone and osteoid volumes using microcomputed tomography or histomorphometric evaluations, demonstrating an additive effect of SVF supplementation, independent of the bone substitute. This study demonstrated for the first time the feasibility, safety, and potential efficacy of SVF seeded on bone substitutes for MSFE, providing the first step toward a novel treatment concept that might offer broad potential for SVF-based regenerative medicine applications. SIGNIFICANCE: This is the first-in human study using freshly isolated, autologous adipose stem cell preparations (the stromal vascular fraction [SVF] of adipose tissue) applied in a one-step surgical procedure with calcium phosphate ceramics (CaP) to increase maxillary bone height for dental implantations. All 10 patients received CaP plus SVF on one side, whereas bilaterally treated patients (6 of 10) received CaP only on the opposite side. This allowed intrapatient evaluation of the potential added value of SVF supplementation, assessed in biopsies obtained after 6 months. Feasibility, safety, and potential efficacy of SVF for bone regeneration were demonstrated, showing high potential for this novel concept. PMID- 27388242 TI - Perivascular Progenitor Cells Derived From Human Embryonic Stem Cells Exhibit Functional Characteristics of Pericytes and Improve the Retinal Vasculature in a Rodent Model of Diabetic Retinopathy. AB - : Diabetic retinopathy (DR) is the leading cause of blindness in working-age people. Pericyte loss is one of the pathologic cellular events in DR, which weakens the retinal microvessels. Damage to the microvascular networks is irreversible and permanent; thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human embryonic stem cells (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells with a natural selection method without cell-sorting processes. As a cellular model of pericytes, hESC PVPCs exhibited marker expressions such as CD140B, CD146, NG2, and functional characteristics of pericytes. Following a single intravitreal injection into diabetic Brown Norway rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature and stabilized the blood retinal barrier breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization. SIGNIFICANCE: This study provides a simple and feasible method to generate perivascular progenitor cells from human embryonic stem cells. These cells share functional characteristics with pericytes, which are irreversibly lost at the onset of diabetic retinopathy. Animal studies demonstrated that replenishing the damaged pericytes with perivascular progenitor cells could restore retinal vascular integrity and prevent fluid leakage. This provides promising and compelling evidence that perivascular progenitor cells can be used as a novel therapeutic agent to treat diabetic retinopathy patients. PMID- 27388243 TI - Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis. AB - : : The incidence of idiopathic pulmonary fibrosis is on the rise and existing treatments have failed to halt or reverse disease progression. Mesenchymal stromal cells (MSCs) have potent cytoprotective effects, can promote tissue repair, and have demonstrated efficacy in a range of fibrotic lung diseases; however, the exact mechanisms of action remain to be elucidated. Chemical antagonists and short hairpin RNA knockdown were used to identify the mechanisms of action used by MSCs in promoting wound healing, proliferation, and inhibiting apoptosis. Using the bleomycin induced fibrosis model, the protective effects of early or late MSC administration were examined. The role for hepatocyte growth factor (HGF) in MSC protection against bleomycin lung injury was examined using HGF knockdown MSC. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling assay was performed on ex vivo lung sections to examine the effects of MSC on apoptosis. MSC conditioned media (CM) enhanced wound closure and inhibited apoptosis of pulmonary cells in vitro. HGF was required for MSC CM enhancement of epithelial cell proliferation and inhibition of apoptosis. In contrast, MSC required COX-2 for CM to inhibit fibroblast proliferation. In a murine model, early administration of MSC protected against bleomycin induced lung fibrosis and correlated with reduced levels of the proinflammatory cytokine interleukin-1beta, reduced levels of apoptosis, and significantly increased levels of HGF. These protective effects were in part mediated by MSC derived HGF as HGF knockdown MSC were unable to protect against fibrosis in vivo. These findings delineate the mechanisms of MSC protection in a preclinical model of fibrotic lung disease. SIGNIFICANCE: The mechanisms used by mesenchymal stromal cells (MSCs) in mediating protective effects in chronic models of lung disease are not understood and remain to be elucidated. These findings from in vitro studies highlight an important role for the MSC-derived soluble factors hepatocyte growth factor (HGF) and prostaglandin E2 in promoting wound healing and inhibiting apoptosis. Furthermore, this study translates these findings demonstrating an important role for HGF in the protective effects mediated by MSC in vivo in the bleomycin model. These findings support a targeted approach to enhancing MSC therapy for fibrotic disease and highlight the importance of timing of MSC therapy. PMID- 27388245 TI - S100A8 and S100A9 proteins are expressed by human corneal stromal dendritic cells. AB - BACKGROUND/AIMS: The limbus is a remarkable anatomical site endowed with specialised functions to ensure corneal health and transparency, which is essential for exquisite vision. Cell types that contribute to homeostasis and the disease-free state of the cornea include epithelial and stromal stem cells, and antigen-presenting dendritic cells (DCs). DCs are found throughout the corneal epithelium and stroma, but the protein markers that discriminate between cells in different locations have not been properly identified. S100 proteins are expressed in normal and diseased ocular surfaces and are implicated in DC differentiation. METHODS: This study used transplant quality human cadaveric donor corneas (n=6) and immunofluorescence to determine the spatial distributions of S100A8 (A8) and S100A9 (A9), and to characterise the cell types expressing these proteins. RESULTS: A8-expressing and A9-expressing cells were predominantly confined to the limbal stroma and represented 0.25%+/-0.1% and 0.39%+/-0.1%, respectively, of the total stromal cell population. They were phenotyped as CD45(+)/HLA-DR(+)/CD11c(+), markers characteristic of DCs. Interestingly, A8 and A9 immunoreactivity was only associated with stromal DCs, but not those entrenched in the epithelium. CONCLUSIONS: A8 and A9 expression may distinguish between subpopulations of DC that reside in different regions of the human cornea and may influence their maturation status. PMID- 27388244 TI - Concise Review: Recent Advances in the In Vitro Derivation of Blood Cell Populations. AB - : : Hematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. Embryonic stem cell-based directed differentiation and direct reprogramming of somatic cells provide excellent tools for the potential generation of hematopoietic stem cells usable in the clinic for cellular therapies. In addition to blood stem cell transplantation, mature blood cells such as red blood cells, platelets, and engineered T cells have also been increasingly used to treat several diseases. Besides cellular therapies, induced blood progenitor cells generated from autologous sources (either induced pluripotent stem cells or somatic cells) can be useful for disease modeling of bone marrow failures and acquired blood disorders. However, although great progress has been made toward these goals, we are still far from the use of in vitro-derived blood products in the clinic. We review the current state of knowledge on the directed differentiation of embryonic stem cells and the reprogramming of somatic cells toward the generation of blood stem cells and derivatives. SIGNIFICANCE: Hematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. The current state of knowledge on the directed differentiation of embryonic stem cells and the reprogramming of somatic cells toward the generation of blood stem cells and derivatives is reviewed. PMID- 27388246 TI - The association between systemic vascular endothelial growth factor and retinopathy of prematurity in premature infants: a systematic review. AB - Retinopathy of prematurity (ROP), a vasoproliferative disorder exclusive to premature infants is an important cause of childhood blindness. The number of premature infants surviving with this condition is expected to increase globally. Animal models of oxygen-induced retinopathy studies have shown vascular endothelial growth factor (VEGF) to be a key player in the pathogenesis of ROP. This has led to increased use of VEGF antagonist as an alternative treatment for ROP. The purpose of this systematic review is to determine the association between VEGF and ROP in human newborn. The literature review identified 12 studies to date which fulfilled the search criteria. Investigators used cord blood, serum, plasma and tissue samples to investigate the association between ROP and VEGF. Studies that measured VEGF in cord blood found mixed results, with low VEGF (at birth) associated with ROP in one study and no difference noted in two others. Mixed results were also seen in studies determining VEGF in postnatal venous samples. Four studies showed no difference in VEGF level between premature infants with and without ROP, one study showed an increased VEGF level in premature infants with ROP and another study found serum VEGF to be low in premature infants with ROP. The most recent study demonstrated an initial increase in serum VEGF followed by a decline at the time of treatment. These contradictory results indicate that we are yet to fully understand the role of VEGF in human premature infants and question the rationale of treating ROP with anti-VEGF. Anti-VEGF therapy results in systemic effect on serum VEGF levels for up to 2 months and this could have an effect on neurodevelopmental outcome. The effect of this on other developing organs is currently unknown. More studies are required to determine the mechanistic relationships between systemic VEGF and ROP in premature infants. PMID- 27388247 TI - Case-control study of risk factors for acute corneal hydrops in keratoconus. AB - PURPOSE: To determine risk factors for the development of acute corneal hydrops in keratoconus in the UK in a case-controlled study. METHODS: Between November 2009 and December 2010, we prospectively identified 73 individuals who developed acute corneal hydrops. We then identified 174 controls from nine regions in the UK with keratoconus who had not had hydrops. For cases and controls we recorded demographics and clinical features. Univariate and multivariable logistic regressions were performed to identify risk factors. RESULTS: Univariate analysis suggested strong associations between the odds of hydrops and each of vernal keratoconjunctivitis (OR 4.08, 95% CI 1.45 to 11.49, p=0.008), asthma (OR 2.70, CI 1.34 to 5.47, p=0.006), atopic dermatitis (OR 3.13, CI 1.50 to 6.56, p=0.002), learning difficulties (OR 7.84, CI 2.86 to 21.46, p<0.001), previous hydrops (OR 40.2; CI 6.2 to infinity, p<0.001), black ethnicity (OR 2.98, CI 0.98 to 8.99; p=0.05), visual acuity in the worse eye (OR 8.76 CI 3.86 to 19.88; p<0.001) and minimum keratometry of >=48 D prior to the hydrops (OR 4.91, CI 1.07 to 22.6, p=0.041). The use of a contact lens correction was also found to be associated with the odds of hydrops (OR 0.08; CI 0.03 to 0.19, p<0.001). Multiple variable regression indicated that having vernal keratoconjunctivitis (adjusted OR (AOR) 15, 95% CI 1.30 to 173.7; p=0.03), asthma (AOR 4.92, CI 1.22 to 19.78; p=0.025), visual acuity in worse eye (AOR 4.11, CI 1.18 to 14.32; p=0.026) and a high keratometry value (AOR 4.44, CI 0.85 to 23.18; p=0.077) were independently associated with the odds of hydrops in subjects with keratoconus. CONCLUSION: Some individuals with keratoconus are at high risk of developing acute corneal hydrops. These patients could be managed more aggressively to reduce their risk of developing this complication of their disease. PMID- 27388248 TI - Structural analyses of choroid after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy. AB - BACKGROUND/AIMS: To investigate the changes in the intrachoroidal structures after half-dose verteporfin photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). METHODS: Swept-source optical coherence tomography cross sectional images of 22 eyes of 22 patients with CSC were retrospectively analysed by a manual delineation technique and binarisation method. RESULTS: In the 22 eyes, the mean subfoveal choroidal thickness decreased from 412.9+/-112.9 MUm at baseline to 340.0+/-111.0 MUm at 3 months (p<0.0001). The mean thickness of the large choroidal vessel layer decreased from 368.7+/-112.7 MUm at baseline to 292.2+/-118.0 MUm at 3 months (p<0.0001), but the mean choriocapillaris-medium choroidal vessel layer thickness did not change from 44.2+/-29.2 MUm at baseline to 47.8+/-25.7 MUm at 3 months (p=0.85). Analyses of the binarised choroidal images showed that a 3 mm subfoveal choroidal area decreased from 1.141+/-0.290 mm2 at baseline to 0.962+/-0.320 mm2 at 3 months after PDT (p=0.0001). The mean luminal areas decreased from 0.826+/-0.246 mm2 at baseline to 0.665+/-0.234 mm2 at 3 months (p=0.0001), however, the mean stromal areas did not change from 0.315+/-0.066 mm2 at baseline to 0.297+/-0.095 mm2 at 3 months (p=0.60). CONCLUSIONS: Half-dose PDT reduces subfoveal choroidal thickness and alters the intrachoroidal structures in eyes with CSC. PMID- 27388249 TI - Crowded letter and crowded picture logMAR acuity in children with amblyopia: a quantitative comparison. AB - AIMS: Clinically, picture acuity tests are thought to overestimate visual acuity (VA) compared with letter tests, but this has not been systematically investigated in children with amblyopia. This study compared VA measurements with the LogMAR Crowded Kay Picture test to the LogMAR Crowded Keeler Letter acuity test in a group of young children with amblyopia. METHODS: 58 children (34 male) with amblyopia (22 anisometropic, 18 strabismic and 18 with both strabismic/anisometropic amblyopia) aged 4-6 years (mean=68.7, range=48-83 months) underwent VA measurements. VA chart testing order was randomised, but the amblyopic eye was tested before the fellow eye. All participants wore up-to-date refractive correction. RESULTS: The Kay Picture test significantly overestimated VA by 0.098 logMAR (95% limits of agreement (LOA), 0.13) in the amblyopic eye and 0.088 logMAR (95% LOA, 0.13) in the fellow eye, respectively (p<0.001). No interactions were found from occlusion therapy, refractive correction or type of amblyopia on VA results (p>0.23). For both the amblyopic and fellow eyes, Bland Altman plots demonstrated a systematic and predictable difference between Kay Picture and Keeler Letter charts across the range of acuities tested (Keeler acuity: amblyopic eye 0.75 to -0.05 logMAR; fellow eye 0.45 to -0.15 logMAR). Linear regression analysis (p<0.00001) and also slope values close to one (amblyopic 0.98, fellow 0.86) demonstrate that there is no proportional bias. CONCLUSIONS: The Kay Picture test consistently overestimated VA by approximately 0.10 logMAR when compared with the Keeler Letter test in young children with amblyopia. Due to the predictable difference found between both crowded logMAR acuity tests, it is reasonable to adjust Kay Picture acuity thresholds by +0.10 logMAR to compute expected Keeler Letter acuity scores. PMID- 27388250 TI - Epithelium-off versus transepithelial corneal collagen crosslinking for progressive corneal ectasia: a randomised and controlled trial. AB - AIM: To compare the outcomes of corneal collagen crosslinking (CXL) for the treatment of progressive corneal ectasia using a standard epithelium-off technique versus a transepithelial technique with enhanced riboflavin solution. METHODS: One hundred and forty-four eyes with progressive corneal ectasia were prospectively randomised into a transepithelial CXL study arm or an epithelium off CXL control arm. Follow-up examinations were set at 3, 6, 12 and 24 months. The primary outcome measure was change in the maximum simulated keratometry value (Ksteep) after 24 months of follow-up. The secondary outcome measure was change in the best spectacle-corrected visual acuity (BSCVA) after 24 months follow-up. RESULTS: One hundred and thirty-one eyes completed the 24-month follow-up interval. Change in Ksteep was -1.52+/-0.66 dioptres (D) for the control group versus -0.54+/-0.58 D for the study group at 24 months of follow-up (p=0.0320). Change in BSCVA was -0.18+/-0.09 logMAR for the control group versus -0.14+/-0.08 logMAR for the study group at 24 months of follow-up (p=0.4978). Two eyes in the control group had minor postoperative complications that did not affect the final visual acuity, and one eye in the control group underwent keratoplasty during the study interval. CONCLUSIONS: At 24 months of follow-up, subjects in the epithelium-off CXL group demonstrated a greater improvement in Ksteep compared with subjects in the transepithelial CXL group, but no statistically significant difference in BSCVA was found between groups. TRIAL REGISTRATION NUMBER: NCT01708538; pre-results. PMID- 27388251 TI - Prospective randomised clinical trial to evaluate the safety and efficacy of nepafenac 0.1% treatment for the prevention of macular oedema associated with cataract surgery in patients with diabetic retinopathy. AB - BACKGROUND/AIMS: This study evaluated nepafenac ophthalmic suspension 0.1% for prevention of macular oedema (MO) when used 90 days following cataract surgery in patients with diabetic retinopathy (DR). METHODS: Randomised, double-masked, vehicle-controlled, parallel group study conducted at 32 centres across the world. Participants were patients with diabetes with non-proliferative diabetic retinopathy scheduled for cataract surgery with (posterior chamber) intraocular lens implantation. Patients were randomised to nepafenac ophthalmic suspension 0.1% or vehicle three times daily, beginning on the day before surgery and continuing through the last study visit (day 90 or early exit). All patients were instilled one drop of tobramycin 0.3% and dexamethasone 0.1% four times daily for 2 weeks after surgery. Primary efficacy end point was the percentage of patients who developed MO (defined as >=30% increase in central subfield macular thickness from baseline) within 90 days following surgery. The secondary end point was mean change in best-corrected visual acuity (BCVA) from baseline to day 90. RESULTS: A total of 175 patients were randomised, with 87 and 88 patients in the nepafenac and vehicle groups, respectively. A significantly greater percentage of eyes in the vehicle group (17.5%; 95% CI 9.9% to 27.6%) developed MO within 90 days following surgery compared with the nepafenac group (5.0%; 95% CI 1.4% to 12.3%, p=0.01). Mean change in BCVA from baseline to day 90 following surgery was greater in the nepafenac group (17.7+/-14.6 letters) relative to the vehicle group (14.3+/-13.9 letters), though the difference was not statistically significant (p=0.14). No new safety issues or trends were identified. CONCLUSIONS: A 90-day nepafenac treatment regimen prevented MO after cataract surgery in patients with DR and demonstrated no safety issues within this study group. TRIAL REGISTRATION NUMBER: NTC00782717 and NCT00939276. PMID- 27388252 TI - Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging. AB - BACKGROUND/AIMS: To determine the morphological features of anterior scleral inflammation using swept-source optical coherence tomography. METHODS: In this retrospective observational study, we examined 17 eyes of 14 patients with diffuse anterior scleral inflammation and 13 eyes of 13 young unaffected patients. We compared cross-sectional images of the conjunctiva, episclera and sclera obtained using swept-source optical coherence tomography equipped with a multiple B-scan averaging process between normal eyes and those with episcleritis and scleritis. RESULTS: Optical coherence tomography showed that the conjunctival stroma/episclera layer was notably swollen in diseased eyes. The eyes with diffuse anterior scleral inflammation had a significantly thicker conjunctival stroma/episclera than normal eyes (403.0 MUm vs 288.0 MUm, p=0.002). There was no significant difference in scleral stroma thickness between eyes with anterior scleral inflammation and normal eyes (464.7 MUm vs 434.2 MUm, p=0.11). We separately analysed 11 eyes with diffuse scleritis and 6 eyes with diffuse episcleritis. While the conjunctival epithelium and conjunctival stroma/episclera were thicker in eyes with diffuse scleritis than in those with diffuse episcleritis (78.9 MUm vs 50.4 MUm, p=0.003 and 445.5 MUm vs 308.8 MUm, p=0.033, respectively), the scleral stroma thickness in eyes with diffuse scleritis was comparable with normal eyes (465.5 MUm vs 434.2 MUm, p=0.43). CONCLUSIONS: The swelling of diffuse scleritis occurred within the episclera rather than in the scleral stroma. Since optical coherence tomography visualises the morphology of the episclera and sclera, it can be useful for evaluating inflammation activity and therapeutic effects in diffuse scleritis. PMID- 27388253 TI - Copy number and expression analysis of FOSL1, GSTP1, NTSR1, FADD and CCND1 genes in primary breast tumors with axillary lymph node metastasis. AB - In breast cancer, lymph node (LN) metastasis is one of the strongest prognostic factors at diagnosis. Therefore the identification of molecular markers with metastatic potential that promote the development of LN metastasis is of critical clinical relevance. In this study, we evaluated the copy number status of the FOSL1, GSTP1, NTSR1, FADD and CCND1 genes by TaqMan assays in 137 breast cancer patients, 84 with LN metastasis (LN+) and 53 with no LN metastasis (LN-). The copy number data for four of these genes (FOSL1, GSTP1, FADD and CCND1) were integrated with their mRNA expression levels in 31 patients. In both groups of patients, gains were the most frequent copy number alteration (CNA) observed, involving mainly the CCND1, NTSR1 and FADD genes; mRNA overexpression was more commonly observed for the CCND1 and FADD genes. For the FADD gene in the LN+ group, gene expression was shown to be dependent on CNAs; for the other genes no association was found. In conclusion, increase copy number and mRNA overexpression of FOSL1, GSTP1, FADD, NTSR1 and CCND1 genes are frequently observed in primary breast tumors, and except for the FADD gene, they occur independently and irrespectively of the patients' LN axillary metastatic status. PMID- 27388254 TI - New perspectives on forced migration in the history of twentieth-century neuroscience. AB - This special issue of the Journal of the History of the Neurosciences, comprised of six articles and one commentary, reflects on the multifold dimensions of intellectual migration in the neurosciences and illustrates them by relevant case studies, biographies, and surveys from twentieth-century history of science and medicine perspectives. The special issue as a whole strives to emphasize the impact of forced migration in the neurosciences and psychiatry from an interdisciplinary perspective by, first, describing the general research topic, second, by showing how new models can be applied to the historiography and social studies of twentieth-century neuroscience, and, third, by providing a deeper understanding of the impact of European emigre researchers on emerging allied fields, such as neurogenetics, biological psychiatry, psychosomatics, and public mental health, etc. as resulting from this process at large. PMID- 27388255 TI - Eugenics ideals, racial hygiene, and the emigration process of German-American neurogeneticist Franz Josef Kallmann (1897-1965). AB - Biological psychiatry in the early twentieth century was based on interrelated disciplines, such as neurology and experimental biology. Neuropsychiatrist Franz Josef Kallmann (1897-1965) was a product of this interdisciplinary background who showed an ability to adapt to different scientific contexts, first in the field of neuromorphology in Berlin, and later in New York. Nonetheless, having innovative ideas, as Kallmann did, could be an ambiguous advantage, since they could lead to incommensurable scientific views and marginalization in existing research programs. Kallmann followed his Dr. Med. degree (1919) with training periods at the Charite Medical School in Berlin under psychiatrist Karl Bonhoeffer (1868-1948). Subsequently, he collaborated with Ernst Ruedin (1874 1952), investigating sibling inheritance of schizophrenia and becoming a protagonist of genetic research on psychiatric conditions. In 1936, Kallmann was forced to immigrate to the USA where he published The Genetics of Schizophrenia (1938), based on data he had gathered from the district pathological institutes of Berlin's public health department. Kallmann resumed his role as an international player in biological psychiatry and genetics, becoming president (1952) of the American Society of Human Genetics and Director of the New York State Psychiatric Institute in 1955. While his work was well received by geneticists, the idea of genetic differences barely took hold in American psychiatry, largely because of emigre psychoanalysts who dominated American clinical psychiatry until the 1960s and established a philosophical direction in which genetics played no significant role, being regarded as dangerous in light of Nazi medical atrocities. After all, medical scientists in Nazi Germany had been among the social protagonists of racial hygiene which, under the aegis of Nazi philosophies, replaced medical genetics as the basis for the ideals and application of eugenics. PMID- 27388256 TI - A variation on forced migration: Wilhelm Peters (Prussia via Britain to Turkey) and Muzafer Sherif (Turkey to the United States). AB - In 1933 the Turkish Republic formally offered university positions to 30 German speaking academics who were dismissed with the coming to power of the National Socialist Government. That initial number went up to 56 with the inclusion of the technical assistants. By 1948 the estimated total had increased to 199. Given renewable five-year contracts with salaries substantially higher than their Turkish counterparts, the foreign emigres were to implement the westernization program of higher education. The ten year-old secular Turkish Republic's extensive social reforms had encompassed the adoption of the Latin alphabet, and equal rights for women, removing gender bias in hiring. Such a high concentration of emigre academics in one institution, "the highest anywhere in the world," provides a unique opportunity to study a subject which has been neglected. In this article two cases in psychology will be examined: Wilhelm Peters (1880 1963), who came, via Britain, to Istanbul in 1936 from the University of Jena in Germany, and Muzafer Sherif (1906-1988) who went to the United States from Ankara University in 1945. The purpose of the comparative analysis is to identify the features that are specific to the German experience, and those that are shared and underlie translocation in science within the multifaceted complexity of the process of forced migration. PMID- 27388257 TI - Between resentment and aid: German and Austrian psychiatrist and neurologist refugees in Great Britain since 1933. AB - This article is a historiographical exploration of the experiences that German and Austrian emigre psychiatrists and neurologists made in Great Britain since 1933, after the Nazi Governments in Central Europe had ousted them from their positions. When placing these occurrences in a wider historiographical perspective, the in-depth analysis provided here also describes the living and working conditions of the refugee neuroscientists on the British Isles. In particular, it looks at the very elements and issues that influenced the international forced migration of physicians and psychiatrists during the 1930s and 1940s. Only a fraction of refugee neuroscientists had however been admitted to Britain. Those lucky ones were assisted by a number of charitable, local, and academic organizations. This article investigates the rather lethargic attitude of the British government and medical circles towards German-speaking Jewish refugee neuroscientists who wished to escape Nazi Germany. It will also analyze the help that those refugees received from the academic establishment and British Jewish organizations, while likewise examining the level and extent of the relationship between social and scientific resentments in Great Britain. A special consideration will be given to the aid programs that had already began in the first year after the Nazis had seized power in Germany, with the foundation of the British Assistance Council by Sir William Henry Beveridge (1879-1963) in 1933. PMID- 27388258 TI - Emigre scientists and the global turn in the history of science: A commentary on the special issue "New Perspectives on Forced Migration in the History of Twentieth-Century Neuroscience". PMID- 27388259 TI - Individual and group psychotherapy with people diagnosed with dementia: a systematic review of the literature. AB - OBJECTIVES: Psychotherapy provides a means of helping participants to resolve emotional threats and play an active role in their lives. Consequently, psychotherapy is increasingly used within dementia care. This paper reviews the existing evidence base for individual and group psychotherapy with people affected by dementia. DESIGN: The protocol was registered. We searched electronic databases, relevant websites and reference lists for records of psychotherapy with people affected by Alzheimer's Disease, Vascular dementia, Lewy-body dementia or a mixed condition between 1997 and 2015. We included studies of therapies which met British Association of Counselling and Psychotherapy definitions (e.g. occurs regularly, focuses on talking about life events and facilitates understand of the illness). Art therapy, Cognitive Stimulation and Rehabilitation, Life Review, Reminiscence Therapy and family therapy were excluded. Studies which included people with frontal-temporal dementia and mild cognitive impairment were excluded. Data was extracted using a bespoke form, and risk of bias assessments were carried out independently by both authors. Meta analysis was not possible because of the heterogeneity of data. RESULTS: A total of 1397 papers were screened with 26 papers using randomised, non-randomised controlled trials or repeated measured designs being included. A broad mix of therapeutic modalities, types, lengths and settings were described, focussing largely on people with mild levels of cognitive impairment living in the community. CONCLUSIONS: This study was limited to only those studies published in English. The strongest evidence supported the use of short-term group therapy after diagnosis and an intensive, multi-faceted intervention for Nursing Home residents. Many areas of psychotherapy need further research. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388260 TI - Psychological well-being of older Chinese immigrants living in Australia: a comparison with older Caucasians. AB - BACKGROUND: Few current studies explore psychological well-being among older Chinese immigrants in Australia. The study addressed this gap and provided preliminary data on psychological well-being among this group. Four indicators, namely depression, anxiety, loneliness, and quality of life, were used to present a comprehensive picture of psychological well-being. METHODS: Participants were two groups of community-dwelling older people, specifically 59 Chinese immigrants and 60 Australian-born people (median age=77 and 73, respectively). Data were collected through standardized interviews. The Geriatric Depression Scale, the Hospital Anxiety and Depression Scale, the de Jong Gierveld Loneliness Scale and the WHO Quality of Life questionnaire were used to measure depression, anxiety, loneliness, and quality of life, respectively. RESULTS: Chinese participants' median quality of life score was higher than the scale mid-point, indicating relatively high levels of quality of life. However, 10% exhibited symptoms of depression, 6% had symptoms of anxiety, and 49% felt lonely. Compared to Australian participants, Chinese participants reported poorer quality of life and higher levels of loneliness. Importantly, the difference in quality of life remained when the impact of socio-demographic factors was controlled for. CONCLUSIONS: This study was the first to use multiple indicators to explore psychological well-being among older Chinese immigrants in Australia. Its results suggest that their psychological well-being might be worse than that of Australian-born people when using loneliness and quality of life as indicators. In particular, loneliness is a common psychological problem among this group, and there is a need for public awareness of this problem. PMID- 27388261 TI - From current status to optimization of HCV treatment: Recommendations from an expert panel. AB - Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper. PMID- 27388262 TI - Basal values and changes of liver stiffness predict the risk of disease progression in compensated advanced chronic liver disease. AB - BACKGROUND AND AIMS: Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD). METHODS: Ninety-four patients with baseline LSM >=10kPa, Child-Pugh score 5 and without previous decompensation were included. A second LSM was performed during follow up and data on liver function and liver-related events were collected. The primary endpoint was a composite that included death, liver decompensation and impairment in at least 1 point in Child-Pugh score. RESULTS: After a median follow-up of 43.6 months, 15% of patients presented the primary endpoint. Multivariate analysis identified baseline LSM (OR 1.12, P=0.002) and delta-LSM (OR 1.02, P=0.048) as independent predictors of the primary endpoint. A high risk group represented by patients with baseline LSM >=21kPa and delta-LSM >=10% (risk of progression 47.1%, 95% CI: 23-71%) was identified, while patients with LSM <21kPa and delta-LSM <10% presented zero risk of progression (P=0.03). CONCLUSIONS: Simple classification rules using baseline LSM and delta-LSM identify cACLD patients at low or high risk of disease progression. PMID- 27388263 TI - Characterization of iron-sulfur clusters in flavin-containing opine dehydrogenase. AB - Flavin-containing opine dehydrogenase from Bradyrhizobium japonicum forms a heterooligomeric alpha4beta4gamma4 enzyme complex. An electron paramagnetic resonance spectroscopy analysis using wild-type and site-directed mutants revealed that [4Fe-4S] and [2Fe-2S] clusters bind to two different types of [Fe S] binding sites in the gamma- and alpha-subunits, respectively. The latter was found to be important for structural folding and enzyme catalysis. PMID- 27388264 TI - Prevention of ventilator-associated pneumonia: Use of the care bundle approach. AB - BACKGROUND: The ventilator-associated pneumonia (VAP) care bundle consists of evidence-based practices to improve the outcomes of patients receiving mechanical ventilatory therapy. This study aimed to investigate the implementation of the care bundle on VAP rates in this quasiexperimental study. METHODS: The protocol of this study consisted of 3 phases. In the initial phase, observations were made to determine the VAP care bundle adherence of intensive care unit (ICU) nurses. In the second phase, education was provided to ICU nurses on the subject of the VAP care bundle. For the third phase, the effect of VAP care bundle adherence on the VAP rates after education was investigated. RESULTS: The nurses' VAP care bundle adherence improved after education from 10.8% (n = 152) to 89.8% (n = 1,324) and showed statistically significant improvement (P = .0001 and P < .05). In this study, the VAP rates were determined as 15.91/103 ventilator-days before education and 8.50/103 ventilator days after education. It was found that the VAP rates after the education period were significantly lower than the VAP rates before education. CONCLUSION: VAP care bundle implementation with education prepared according to evidence-based guidelines decreased VAP rates. Thus, implementation of the VAP care bundle on mechanically ventilated patients care is recommended. PMID- 27388265 TI - Airborne pathogen isolation capability in emergency departments of US children's hospitals. AB - The requirement for negative pressure isolation procedures has been an accepted component of pediatric care to protect patients and staff from highly infectious respiratory agents. Surveys regarding airborne isolation were distributed to 43 pediatric emergency departments at US children's hospitals with 26 responses. There was a median of 5 airborne isolation rooms, a median of 4 of those with negative pressure, and 61% without an ante-room. Capacity to manage pediatric patients infected with a highly pathogenic airborne-transmitted organism during an epidemic is limited. PMID- 27388266 TI - Bacteria emitted in ambient air during bronchoscopy-a risk to health care workers? AB - BACKGROUND: Health care workers are at risk of occupational infections, and some procedures are known to increase this risk. The aim of this study was to qualify and quantify bioaerosol concentrations during bronchoscopy to estimate the occupational risk. METHODS: Full-day sampling was conducted in 2 rooms while bronchoscopies were performed on patients. Two microbial air samplers were used, a wet wall cyclonic sampler and an impactor, on culture media. Identification of the culturable bacterial flora was performed with chromatographic analysis of cellular fatty acid of the isolated strain and additional biochemical tests if needed. Specific polymerase chain reaction analysis was completed on wet wall cyclonic samples for the detection of influenza A and B and Mycobacterium spp. RESULTS: A wide variety of bacteria were collected from the ambient air. All samples yielded at least 1 Staphylococcus species. Although most of the culturable bacteria identified were normal nonpathogenic flora, such as Streptococcus spp, Neisseria spp, and Corynebacterium spp, some opportunistic pathogens, such as Streptococcus pneumoniae, were found. Neither Mycobacterium spp nor influenza virus was detected with the polymerase chain reaction method during this study. CONCLUSIONS: Culturable bacteria from oral, nasal, and pulmonary flora are aerosolized during bronchoscopy and could be inhaled by medical staff. The potential presence of pathogens in those aerosols could represent an occupational infection risk. PMID- 27388267 TI - Influence of material properties on gloves' bacterial barrier efficacy in the presence of microperforation. AB - BACKGROUND: Medical examination gloves and surgical gloves protect the wearer directly and the patient indirectly from the risk of contamination. Because of concerns related to latex allergy, an increasing trend toward the use of synthetic gloves made of materials other than latex is observable. However, currently it is unknown if the physical properties of different materials may influence bacterial passage in case of a glove puncture. METHODS: We examined 9 different medical examination gloves from various manufacturers made of nitrile (n = 4), latex (n = 3), or neoprene (n = 2). Additionally, 1 latex surgical glove each with and without antibacterial chlorhexidine gluconate coating and 1 synthetic surgical glove made of thermoplastic elastomer were included in the experiments. The studied materials were perforated following a standardized procedure, and direct bacterial passage was measured under dynamic conditions. Glove elasticity at 1 cm up to 2.5 cm elongation was measured following EN 455-2. RESULTS: Nitrile gloves demonstrated higher material stiffness compared with latex gloves. Medical examination gloves made of nitrile and neoprene showed a 10 fold higher bacterial passage through a standardized puncture compared with latex gloves. All surgical gloves showed a lower bacterial passage compared with the tested examination gloves. CONCLUSION: Bacterial passage through punctures is correlated with the stiffness or elasticity of the glove material. Therefore, gloves made of latex may have an increased protective effect in case of a glove breach. Whenever gloves are purchased and selected, a risk-benefit assessment should be conducted, balancing the risk of allergy against the degree of required protection in case of a glove puncture. PMID- 27388268 TI - Male veterans with complicated urinary tract infections: Influence of a patient centered antimicrobial stewardship program. AB - BACKGROUND: The influence of antimicrobial stewardship programs (ASPs) on outcomes in male veterans treated for complicated urinary tract infection has not been determined. METHODS: This was a retrospective cohort study encompassing the study period January 1, 2005-October 31, 2014, which was conducted at a 150-bed Veterans Affairs Healthcare System facility in Buffalo, NY. Male veterans admitted for treatment of complicated urinary tract infection were identified using ICD-9-CM codes. Outcomes before and after implementation of a patient centered ASP, including duration of antibiotic therapy, length of hospitalization, readmission within 30 days, and Clostridium difficile infection were compared. Interventions resulting from the ASP were categorized. RESULTS: Of the 1,268 patients screened, 241 met criteria for inclusion in the study (n = 118 and n = 123 in the pre-ASP and ASP group, respectively). Duration of antibiotic therapy was significantly shorter in the ASP group (10.32 days vs 11.96 days; P < .0001), as was length of hospitalization (5.76 days vs 6.76 days; P = .015). There was no difference in 30-day readmission. A total of 170 interventions were identified that resulted from the ASP (1.39 interventions per patient). CONCLUSIONS: ASPs may be useful to improve clinical outcomes in men with complicated urinary tract infection. Implementation of an ASP was associated with significant decreases in duration of antibiotic therapy and length of hospitalization, without adversely affecting 30-day readmission rates. PMID- 27388269 TI - Acquisition of bacteria on health care workers' hands after contact with patient privacy curtains. AB - To determine whether pathogenic bacteria could be transferred to health care workers by touching privacy curtains, imprints of health care workers' fingertips were obtained when participants were approached, after hand hygiene with alcohol handrub, and directly after handling curtains. Participants' hands were heavily contaminated at baseline, in some cases with potentially pathogenic species. Half of the participants (n = 30) acquired bacteria on their fingertips from handling curtains, illustrating that privacy curtains may be involved in the transmission of infection to emergency department patients. PMID- 27388270 TI - Impaired eye blink classical conditioning distinguishes dystonic patients with and without tremor. AB - INTRODUCTION: Tremor is frequently associated with dystonia, but its pathophysiology is still unclear. Dysfunctions of cerebellar circuits are known to play a role in the pathophysiology of action-induced tremors, and cerebellar impairment has frequently been associated to dystonia. However, a link between dystonic tremor and cerebellar abnormalities has not been demonstrated so far. METHODS: Twenty-five patients with idiopathic isolated cervical dystonia, with and without tremor, were enrolled. We studied the excitability of inhibitory circuits in the brainstem by measuring the R2 blink reflex recovery cycle (BRC) and implicit learning mediated by the cerebellum by means of eyeblink classical conditioning (EBCC). Results were compared with those obtained in a group of age matched healthy subjects (HS). RESULTS: Statistical analysis did not disclose any significant clinical differences among dystonic patients with and without tremor. Patients with dystonia (regardless of the presence of tremor) showed decreased inhibition of R2 blink reflex by conditioning pulses compared with HS. Patients with dystonic tremor showed a decreased number of conditioned responses in the EBCC paradigm compared to HS and dystonic patients without tremor. CONCLUSION: The present data show that cerebellar impairment segregates with the presence of tremor in patients with dystonia, suggesting that the cerebellum might have a role in the occurrence of dystonic tremor. PMID- 27388271 TI - A New Integrated Approach to Taxonomy: The Fusion of Molecular and Morphological Systematics with Type Material in Benthic Foraminifera. AB - A robust and consistent taxonomy underpins the use of fossil material in palaeoenvironmental research and long-term assessment of biodiversity. This study presents a new integrated taxonomic protocol for benthic foraminifera by unequivocally reconciling the traditional taxonomic name to a specific genetic type. To implement this protocol, a fragment of the small subunit ribosomal RNA (SSU rRNA) gene is used in combination with 16 quantitative morphometric variables to fully characterise the benthic foraminiferal species concept of Elphidium williamsoni Haynes, 1973. A combination of live contemporary topotypic specimens, original type specimens and specimens of genetic outliers were utilised in this study. Through a series of multivariate statistical tests we illustrate that genetically characterised topotype specimens are morphologically congruent with both the holotype and paratype specimens of E. williamsoni Haynes, 1973. We present the first clear link between morphologically characterised type material and the unique SSU rRNA genetic type of E. williamsoni. This example provides a standard framework for the benthic foraminifera which bridges the current discontinuity between molecular and morphological lines of evidence, allowing integration with the traditional Linnaean roots of nomenclature to offer a new prospect for taxonomic stability. PMID- 27388272 TI - Evaluation of a new handheld point-of-care blood gas analyser using 100 equine blood samples. AB - OBJECTIVES: To determine whether the Enterprise point-of-care blood analysis system (EPOC) produces results in agreement with two other blood gas analysers in regular clinical use (i-STAT and Radiometer ABL77) and to investigate the precision of the new machine when used with equine whole blood. STUDY DESIGN: Prospective, randomized, non-blinded, comparative laboratory analyser study. ANIMALS: Horses admitted to a university teaching hospital requiring arterial or venous blood gas analysis as part of their routine clinical management. METHODS: One hundred equine blood samples were run immediately, consecutively and in randomized order on three blood gas analysers. Results of variables common to all three analysers were tested for agreement and compared with guidelines used in human medicine. These require 80% of results from the test analyser to fall within a defined range or percentage of results from the comparator devices to achieve acceptability. Additionally, 21 samples were run twice in quick succession on the EPOC analyser to investigate precision. RESULTS: Agreement targets were not met for haematocrit, haemoglobin and base excess for either i STAT or ABL77 analysers. EPOC precision targets were not met for partial pressure of carbon dioxide, ionized calcium, haematocrit and haemoglobin. Overall comparative performance of the EPOC was good to excellent for pH, oxygen tension, potassium, bicarbonate and oxygen saturation of haemoglobin, but marginal to poor for other parameters. CONCLUSIONS AND CLINICAL RELEVANCE: The EPOC may be useful in performing analysis of equine whole blood, but trend analysis of carbon dioxide tension, ionized calcium, haematocrit and haemoglobin should be interpreted with caution. The EPOC should not be used interchangeably with other blood gas analysers. PMID- 27388273 TI - The effect of the kindergarten barefoot policy on preschool children's toes. AB - BACKGROUND: This study compared the effects of barefoot policy, a policy instructing preschool children to go without shoes, on untouched-toes, which do not touch the ground while standing normally, of preschool children attending kindergartens that follow this rule, to preschooler in kindergartens where they must wear shoes, i.e., no-barefoot policy. METHODS: The study used longitudinal data from measurements taken 2 years apart of the amount of times. The subjects were 59 children (34 boys and 25 girls) who went to a kindergarten that followed barefoot policy and 179 children (103 boys and 76 girls) who went to a kindergarten that did not follow barefoot policy. Images were taken of the contact surface area of the soles of the children's feet by having them stand on the measurement device with their bare feet. RESULTS: The number of untouched toes in children participating in the study was determined from the pictures. In boys who attended kindergartens following barefoot policy, the ratio of the children without untouched-toes significantly increased for 2 years of childhood (35.3-64.7 %). The number of untouched-toes were significantly fewer in boys from kindergartens following barefoot policy than in boys from kindergartens not following the policy, and the magnitude of the difference grew for the two study years (ES: 0.41-0.63). In girls, there were no significant differences between the two groups in the ratio of girls without untouched-toes and the number of untouched-toes. CONCLUSIONS: In conclusion, the ground contact of the toes becomes better for boys in kindergarten with a barefoot policy. The results were inconclusive with regard to girls, and other factors may need to be examined. In the future, it will be necessary to increase the number of the subjects and perform detailed examinations. PMID- 27388274 TI - Relationship between Regional Fat Distribution and Hypertrophic Cardiomyopathy Phenotype. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is characterized by heterogeneous phenotypic expression. Body mass index has been associated with LV mass and heart failure symptoms in HCM. The aim of our study was to investigate whether regional (trunk, appendicular, epicardial) fat distribution and extent could be related to hypertrophy severity and pattern in HCM. METHODS: Cardiovascular magnetic resonance was performed in 32 subjects with echocardiography-based diagnosis of HCM (22M/10F, 57.2+/-12.6 years) characterized by predominant hypertrophy at the interventricular septum (IVS). Regional fat distribution was assessed by dual-energy X-ray absorptiometry. RESULTS: Gender differences were detected in maximum IVS thickness (M: 18.3+/-3.8 mm vs. F: 14.3+/-4 mm, p = 0.012), right ventricle (RV) systolic function (M: 61.3+/-6.7%; F: 67.5+/-6.3%, p = 0.048), indexed RV end-diastolic (M: 64.8+/-16.3 ml/m2; F: 50.7+/-15.5 ml/m2, p = 0.04) and end-systolic volumes (M: 24.3+/-8.3 ml/m2; F: 16.7+/-7.4 ml/m2, p = 0.04). After adjusting for age and gender, maximum IVS thickness was associated with truncal fat (Tr-FAT) (beta = 0.43, p = 0.02), but not with either appendicular or epicardial fat. Epicardial fat resulted independently associated with NT-proBNP levels (beta = 0.63, p = 0.04). Late Gadolinium Enhancement-positive subjects displayed greater maximum IVS thickness (p = 0.02), LV mass index (p = 0.015) and NT-proBNP levels (p = 0.04), but no associations with fat amount or distribution were observed. CONCLUSION: Truncal, but not appendicular or epicardial fat amount, seems to be related with maximum IVS thickness, the hallmark feature in our cohort of HCM patients. Further prospective researches are needed to assess a potential causative effect of central adiposity on HCM phenotype. PMID- 27388275 TI - High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma. AB - BACKGROUND: Serum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma. This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerologia-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate. RESULTS: The abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 <= 500 U/mL was 2.28, 95 % CI 1.08-4.84, P = 0.032. CONCLUSIONS: Clinical stage associated with pretreatment absolute values of CA125 should be considered as prognostic factor in EOC patients. Values of CA125 higher than 500 U/mL in high grade serous carcinoma with FIGO stage III resulted in an enhanced survival rate of the patients. PMID- 27388276 TI - Sound Wave Energy Resulting from the Impact of Water Drops on the Soil Surface. AB - The splashing of water drops on a soil surface is the first step of water erosion. There have been many investigations into splashing-most are based on recording and analysing images taken with high-speed cameras, or measuring the mass of the soil moved by splashing. Here, we present a new aspect of the splash phenomenon's characterization the measurement of the sound pressure level and the sound energy of the wave that propagates in the air. The measurements were carried out for 10 consecutive water drop impacts on the soil surface. Three soils were tested (Endogleyic Umbrisol, Fluvic Endogleyic Cambisol and Haplic Chernozem) with four initial moisture levels (pressure heads: 0.1 kPa, 1 kPa, 3.16 kPa and 16 kPa). We found that the values of the sound pressure and sound wave energy were dependent on the particle size distribution of the soil, less dependent on the initial pressure head, and practically the same for subsequent water drops (from the first to the tenth drop). The highest sound pressure level (and the greatest variability) was for Endogleyic Umbrisol, which had the highest sand fraction content. The sound pressure for this soil increased from 29 dB to 42 dB with the next incidence of drops falling on the sample The smallest (and the lowest variability) was for Fluvic Endogleyic Cambisol which had the highest clay fraction. For all experiments the sound pressure level ranged from ~27 to ~42 dB and the energy emitted in the form of sound waves was within the range of 0.14 MUJ to 5.26 MUJ. This was from 0.03 to 1.07% of the energy of the incident drops. PMID- 27388277 TI - Brain plasticity and migraine transformation: fMRI evidences. AB - INTRODUCTION: Chronification transforms episodic migraine into the pathologic chronic form. Biological characteristics of the migrainous brain progressively change, in predisposed subjects, under the repetition of external and internal stimuli. Modifications involve neurons, synapses, neurotransmitters, receptors, connectivity and pain control. f-MRI is a promising way to explore the still unclear biology of this progression. Areas covered: Data included were obtained from the most relevant and updated works available on PubMed about this topic. We summarized the pathophysiology of migraine chronification and of brain plasticity, and we described the different fMRI techniques and their main evidences about migraine transformation. Expert commentary: Functional-MRI has revealed many aspects regarding the peculiarity of the migrainous brain and its tendency toward chronicity but a series of questions are still open: What are the hallmarks of the predisposition to chronification? Which elements are the cause and which the consequence of this process? PMID- 27388278 TI - A Signal Detection Analysis of the Effects of Alcohol on Visual Contrast Sensitivity. AB - Numerous studies have shown that acute ethanol consumption can reduce visual contrast sensitivity when measured using traditional psychophysical methods. However, no consideration has been given to whether nonsensory factors may also play a role. The present study used both traditional techniques and signal detection procedures to evaluate this possibility. In three within-subject experiments, 41 observers (19 Females and 22 Males) were presented with faint, contrast-modulated, visual patterns and asked to say if they had seen them. In Experiment 1, contrast thresholds were measured using a randomly interleaved staircase procedure, and the data confirmed an increase in threshold following alcohol. In Experiment 2, using similar stimuli, but applying a signal detection analysis, we found that sensitivity, as reflected in d', did not change following alcohol. However, participants became more conservative in their response criterion. The third experiment was designed to allow thresholds to be measured directly with a conventional psychophysical procedure while permitting a signal detection analysis to be performed on the same data. The conventional psychophysical task showed an increase in contrast threshold, while the signal detection analysis showed no change in sensitivity, but a shift to a more conservative criterion. These data highlight the importance of taking into account alcohol's effects on cognitive processes, even when assessing basic sensory function. PMID- 27388279 TI - The CtsR regulator controls the expression of clpC, clpE and clpP and is required for the virulence of Enterococcus faecalis in an invertebrate model. AB - The intrinsic ruggedness of Enterococcus faecalis is responsible for its widespread distribution in nature and is often viewed as an important virulence determinant. Previously, we showed that the ClpB ATPase is negatively regulated by CtsR and is required for thermotolerance and virulence in a Galleria mellonella invertebrate model. Here, we used in silico, Northern blot and quantitative real-time PCR analyses to identify additional members of the CtsR regulon, namely the clpP peptidase and the clpC and clpE ATPases. When compared to the parent strain, virulence of the DeltactsR strain in G. mellonella was significantly attenuated. PMID- 27388280 TI - Efficacy and toxicity of Samen-ista emulsion on treatment of cutaneous and mucosal bleeding. AB - Despite new treatment methods, upper gastrointestinal bleeding remains challenging. Samen-ista emulsion is a new agent based on traditional medicine with coagulant properties. The efficacy and safety of Samen-ista were assessed in cutaneous and mucosal bleeding animal models. Coagulant properties of Samen-ista were evaluated using mice tail bleeding assay, marginal ear vein and upper gastrointestinal mucosal bleeding times in rabbits. After 7 days, clinical signs, mortality and end-organ (kidney, liver, lung, brain and gastric mucosa) histopathological changes were also examined. Samen-ista dose-dependently decreased mean cutaneous tail (128 vs. 14 s) and marginal ear vein (396 vs. 84 s) bleeding times. Rabbit's upper gastrointestinal bleeding time was also significantly decreased (214 vs. 15.8 s) upon Samen-ista local endoscopic application. Treatment with Samen-ista for 7 days did not cause any mortality, abnormal signs of bleeding, changes in appetite or significant histopathologicl changes. Samen-ista emulsion is well tolerated and highly effective in achieving hemostasis in cutaneous and mucosal bleeding animal models. PMID- 27388281 TI - Tranexamic acid decreases the magnitude of platelet dysfunction in aspirin-free patients undergoing cardiac surgery with cardiopulmonary bypass: a pilot study. AB - This study sought to compare the effect of tranexamic acid (TXA) administration on cardiopulmonary bypass-induced platelet dysfunction in patients who received preoperative aspirin or not. We performed a prospective, randomized, double-blind pilot study, including patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). Patients without aspirin interruption were enrolled in the 'group ASPIRIN' (n = 18) and those who had never been treated with aspirin were included in the 'group NO ASPIRIN' (n = 10). Patients were then randomized to receive either TXA or the same infusion of normal saline. Multiple electrode aggregometry was used to assess platelet function at the different time points throughout the surgery: baseline, post-TXA loading dose, aortic unclamping (End CPB), and 5 min after protamine (Protamine). Compared to those included in the group NO ASPIRIN, patients included in the group ASPIRIN presented a decreased baseline platelet function measured by ASP test (P < 0.01) and collagen test (P < 0.01). In the group NO ASPIRIN, treatment group (TXA vs. placebo) significantly influenced the results for ADP test (P < 0.01), thrombin receptor-activating peptide test (P = 0.01), and ASP test (P = 0.01). We observed that TXA improved platelet function, as measured using multiple electrode aggregometry on ADP test, thrombin receptor-activating peptide test, and ASP test, at the end of CPB (P < 0.05). TXA might decrease the magnitude of platelet dysfunction in aspirin-free patients undergoing cardiac surgery. Further studies are needed to confirm these results and assess a potential relationship with clinical endpoints. PMID- 27388282 TI - Incidence and risk factors of deep vein thrombosis (DVT) after total hip or knee arthroplasty: a retrospective study with routinely applied venography. AB - Deep vein thrombosis (DVT) after total hip or knee arthroplasty is relatively common and is associated with significant morbidity and mortality, presenting a large clinical burden. The objective of this study was to investigate the incidence and risk factors for DVT after total joint arthroplasty. This retrospective review was conducted in a single institution. The patients received postoperative DVT chemoprophylaxis (Fraxiparine or Rivaroxaban), followed by venography to check for DVT on the third to ninth postoperative day. The clinical characteristics were summarized and analyzed using SPSS version 17.0. From March 2010 to July 2013, 963 patients were enrolled in the study. DVT chemoprophylaxis was administered to all of the 963 patients. DVT occurred in 173 subjects (17.96%). Univariate analysis showed that age (P < 0.001), BMI (P < 0.01), cholesterol (P < 0.001), high-density lipoprotein (P < 0.001), apolipoprotein A (P < 0.01), history of tumor (P < 0.05), visual analogue scale (VAS) pain score (P < 0.001), and operative duration (P < 0.05) were significant risk factors for DVT. The incidence of DVT was 17.96% after total joint arthroplasty with prophylactic antithrombotic therapy. Age, BMI, cholesterol, high-density lipoprotein, apolipoprotein A, history of tumor, VAS score, and operative duration were significant risk factors for DVT. PMID- 27388283 TI - Were the measurements standardized sufficiently in published studies about mean platelet volume? AB - : Recently, several studies about mean platelet volume (MPV) changes in various pathological conditions were published. The aim of this study was to evaluate the accuracy of the measurement in these studies. The study was performed using the data of 181 studies containing a healthy control groups within 1181 studies about MPV indexed PubMed database since 2012. A total of 81 studies were included retrospectively. The distributions of sex, age, and platelet counts were not reported in 16, 12, and 28 studies, respectively. Type of anticoagulant was not noted in 60 studies. The technology used was not specified in 36 studies. The MPV values measured with Sysmex were significantly higher than measured with Beckman Coulter, Abbott CELL-DYN, and Siemens ADVIA. The MPV measurements varied up to 17.8% by the instruments. The measurement times between 15 min and 2 h was significantly different from the measurement times less than 15 min and more than 2 h. The MPV measurement times from venipuncture were not indicated in 86 studies (47.5%). Maximum deviations in MPV measurements by the MPV measurement times and plus the instruments used varied up to 17.8 and 27.7%, respectively. Both the MPV measurement times and instruments used were not stated in 29 studies (16.0%). Only 47 prospective studies (26.0%) enlightened about the type of anticoagulant, instruments used for MPV measurement, MPV measurement time, platelet counts, and MPV values. As a result, the measurements were not standardized sufficiently in published studies about MPV. It may be explained that the differences between the results of studies made the same pathological conditions. PMID- 27388284 TI - Optimizing the spectral absorption profile of sunscreens. AB - OBJECTIVE: To investigate whether sunscreens provide optimal protection by exhibiting a uniform spectral absorption profile throughout the ultraviolet spectrum or by having a spectral profile in which absorption in the UVB waveband is greater than in the UVA region. METHODS: A sunscreen with a flat spectral absorption profile was compared with one of the same SPF in which the SPF to UVA protection was in the ratio of 3 : 1 in terms of protecting against erythema and chronic effects with different action spectra, as well as the total UV burden to the skin. RESULTS: A sunscreen with spectral profile in which absorption in the UVB waveband is greater than in the UVA region confers no benefit in terms of erythema (and endpoints with similar action spectra) than a sunscreen with the same SPF that exhibits uniform absorption at all wavelengths throughout the UV spectrum. More importantly, the '3 : 1 profile' offers inferior protection when endpoints with other action spectra are considered, as well as resulting in a total UV burden to the skin that is about 5 times higher than sunscreen products showing a flat spectral absorption profile. CONCLUSION: It may be tempting to believe that it is beneficial to increase the absorption of sunscreens in the UVB region relative to the UVA to reflect the fact that skin damage is associated more with UVB than UVA exposure. However, this belief is a fallacy and consumers are best served with sunscreens in which the spectral protection profile is uniform at all wavelengths throughout the UV spectrum. PMID- 27388285 TI - Energy transfer and tunable multicolor emission and paramagnetic properties of GdF3:Dy(3+),Tb(3+),Eu(3+) phosphors. AB - A series of Dy(3+), Tb(3+), Eu(3+) singly or doubly or triply doped GdF3 phosphors were synthesized by a glutamic acid assisted one-step hydrothermal method. The samples were characterized by X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM) and photoluminescence (PL) spectroscopy. The results show that the synthesized samples are all pure GdF3. The obtained samples have a peanut-like morphology with a diameter of about 270 nm and a length of about 600 nm. Under UV excitation, GdF3:Dy(3+), GdF3:Tb(3+) and GdF3:Eu(3+) samples exhibit strong blue, green and red emissions, respectively. By adjusting their relative doping concentrations in the GdF3 host, the different color hues of green and red light are obtained by co-doped Dy(3+), Tb(3+) and Tb(3+), Eu(3+) ions in the GdF3 host, respectively. Besides, there exist two energy transfer pairs in the GdF3 host: (1) Dy(3+) -> Tb(3+) and (2) Tb(3+) -> Eu(3+). More significantly, in the Dy(3+), Tb(3+), and Eu(3+) tri-doped GdF3 phosphors, white light can also be achieved upon excitation of UV light by adjusting the doping concentration of Eu(3+). In addition, the obtained samples also exhibit paramagnetic properties at room temperature (300 K) and low temperature (2 K). It is obvious that multifunctional Dy(3+), Tb(3+), Eu(3+) tri doped GdF3 materials including tunable multicolors and intrinsic paramagnetic properties may have potential applications in the field of full-color displays. PMID- 27388286 TI - Non-Target Impacts of an Attract-and-Kill Formulation Based on Plant Volatiles: Responses of some Generalist Predators. AB - Responses of non-target insects to a blend of plant volatiles used as components in an attract-and-kill formulation for Helicoverpa spp. (Lepidoptera: Noctuidae) were studied in an Australian cotton field. Two experiments, one involving suction sampling during the day and the other at night, were conducted. Rows that had been treated with the volatile blend, with no added insecticide, were sampled with a large suction sampler 18, 42, and 85 h (day experiment) and 6, 30, and 78 h (night experiment) after treatment. Rows located 5, 10, 20, and 300 m away from the treated row were similarly sampled. Of seven generalist predators, only one accumulated on the treated rows compared to the untreated rows. Of the other six, five were found in lower numbers on the treated rows, and for one no significant effects were detected. Compared to pre-spray baseline levels, numbers of several taxa increased across the whole field after spraying, suggesting area-wide attraction, but localized responses to the treated rows were weak, and apparent repellence was more common than attraction. We suggest that attract-and-kill with plant volatiles should have minimal effects on populations of these predators, and is likely to be compatible with integrated pest management. PMID- 27388287 TI - Editorial. PMID- 27388288 TI - Cytokine Therapies in Neurological Disease. AB - Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases. PMID- 27388289 TI - The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease. AB - BACKGROUND: Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload. METHODS: Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group. RESULTS: Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group. CONCLUSIONS: Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the proliferation and increasing the apoptosis of pulmonary arterial smooth muscle cells, and by attenuating the inflammation of pulmonary arteries. PMID- 27388290 TI - Remembering Lyle V. Jones (1924-2016). PMID- 27388291 TI - Causal Inference for Meta-Analysis and Multi-Level Data Structures, with Application to Randomized Studies of Vioxx. AB - We construct a framework for meta-analysis and other multi-level data structures that codifies the sources of heterogeneity between studies or settings in treatment effects and examines their implications for analyses. The key idea is to consider, for each of the treatments under investigation, the subject's potential outcome in each study or setting were he to receive that treatment. We consider four sources of heterogeneity: (1) response inconsistency, whereby a subject's response to a given treatment would vary across different studies or settings, (2) the grouping of nonequivalent treatments, where two or more treatments are grouped and treated as a single treatment under the incorrect assumption that a subject's responses to the different treatments would be identical, (3) nonignorable treatment assignment, and (4) response-related variability in the composition of subjects in different studies or settings. We then examine how these sources affect heterogeneity/homogeneity of conditional and unconditional treatment effects. To illustrate the utility of our approach, we re-analyze individual participant data from 29 randomized placebo-controlled studies on the cardiovascular risk of Vioxx, a Cox-2 selective nonsteroidal anti inflammatory drug approved by the FDA in 1999 for the management of pain and withdrawn from the market in 2004. PMID- 27388292 TI - Effect of cytochrome P450 2C19 polymorphisms on the clinical outcomes of voriconazole: a systematic review and meta-analysis. AB - BACKGROUND: Genetic polymorphisms of cytochrome P450 enzymes, especially CYP2C19, could influence voriconazole pharmacokinetics. The association between CYP2C19 polymorphisms and voriconazole clinical outcomes is not well established. The aim of this meta-analysis was to evaluate the effect of CYP2C19 polymorphisms on clinical outcomes in patients treated with voriconazole. METHODS: PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases were searched from their inception to January 2016 to identify eligible trials that reported voriconazole exposure and clinical outcomes of voriconazole according to CYP2C19 polymorphisms. Two reviewers independently reviewed the citations, extracted the data, and assessed the quality of the trials. The meta-analysis was performed using RevMan5.3. RESULTS: A total of ten studies involving 598 patients were included. Compared with patients with extensive metabolizer (EM) phenotype, patients with poor metabolizer (PM) phenotype had significantly higher trough concentrations (MD, 1.22 mg/L; 95 % confidence interval (CI), 0.72-1.71; P < 0.0001). PM phenotype was also associated with a higher treatment success rate compared with EM phenotype (risk ratio (RR), 1.31; 95 % CI, 1.04-1.67; P = 0.02). However, there was no significant association between CYP2C19 polymorphisms and daily maintenance dose, overall adverse events, hepatotoxicity, and neurotoxicity. CONCLUSIONS: Patients with CYP2C19 PM phenotype were associated with increased treatment success rate and trough concentrations as compared with those with EM phenotype. There was no significant association between CYP2C19 polymorphisms and either daily maintenance dose or adverse outcomes of voriconazole. However, large-scale, high-quality trials are still needed to confirm these findings. PMID- 27388293 TI - Mosquito communities and disease risk influenced by land use change and seasonality in the Australian tropics. AB - BACKGROUND: Anthropogenic land use changes have contributed considerably to the rise of emerging and re-emerging mosquito-borne diseases. These diseases appear to be increasing as a result of the novel juxtapositions of habitats and species that can result in new interchanges of vectors, diseases and hosts. We studied whether the mosquito community structure varied between habitats and seasons and whether known disease vectors displayed habitat preferences in tropical Australia. METHODS: Using CDC model 512 traps, adult mosquitoes were sampled across an anthropogenic disturbance gradient of grassland, rainforest edge and rainforest interior habitats, in both the wet and dry seasons. Nonmetric multidimensional scaling (NMS) ordinations were applied to examine major gradients in the composition of mosquito and vector communities. RESULTS: We captured ~13,000 mosquitoes from 288 trap nights across four study sites. A community analysis identified 29 species from 7 genera. Even though mosquito abundance and richness were similar between the three habitats, the community composition varied significantly in response to habitat type. The mosquito community in rainforest interiors was distinctly different to the community in grasslands, whereas forest edges acted as an ecotone with shared communities from both forest interiors and grasslands. We found two community patterns that will influence disease risk at out study sites, first, that disease vectoring mosquito species occurred all year round. Secondly, that anthropogenic grasslands adjacent to rainforests may increase the probability of novel disease transmission through changes to the vector community on rainforest edges, as most disease transmitting species predominantly occurred in grasslands. CONCLUSION: Our results indicate that the strong influence of anthropogenic land use change on mosquito communities could have potential implications for pathogen transmission to humans and wildlife. PMID- 27388294 TI - The prevalence and health consequences of frailty in a population-based older home care cohort: a comparison of different measures. AB - BACKGROUND: Evaluating different approaches to identifying frail home care clients at heightened risk for adverse health outcomes is an important but understudied area. Our objectives were to determine the prevalence and correlates of frailty (as operationally defined by three measures) in a home care cohort, the agreement between these measures, and their predictive validity for several outcomes assessed over one year. METHODS: We conducted a retrospective cohort study with linked population-based administrative and clinical (Resident Assessment Instrument [RAI]) data for all long-stay home care clients (aged 66+) assessed between April 2010-2013 in Ontario, Canada (n = 234,552). We examined two versions of a frailty index (FI), a full and modified FI, and the CHESS scale, compared their baseline characteristics and their predictive accuracy (by calculating the area under the ROC curve [AUC]) for death, long-term care (LTC) admission, and hospitalization endpoints in models adjusted for age, sex and comorbidity. RESULTS: Frailty prevalence varied by measure (19.5, 24.4 and 44.1 %, for full FI, modified FI and CHESS, respectively) and was similar among female and male clients. All three measures were associated with a significantly increased risk of death, LTC admission and hospitalization endpoints in adjusted analyses but their addition to base models resulted in modest improvement for most AUC estimates. There were significant differences between measures in predictive accuracy, with the full FI demonstrating a higher AUC for LTC admission and CHESS a higher AUC for hospitalization - although none of the measures performed well for the hospitalization endpoints. CONCLUSIONS: The different approaches to detecting vulnerability resulted in different estimates of frailty prevalence among home care clients in Ontario. Although all three measures were significant predictors of the health outcomes examined, the gains in predictive accuracy were often modest with the exception of the full FI in predicting LTC admission. Our findings provide some support for the clinical utility of a comprehensive FI measure and also illustrate that it is feasible to derive such a measure at the population level using routinely collected data. This may facilitate further research on frailty in this setting, including the development and evaluation of interventions for frailty. PMID- 27388295 TI - Spontaneous ureteric rupture, a reality or a faux pas? AB - BACKGROUND: Rupture of the urinary collecting system with or without any perinephric extravasation is an extremely rare occurrence and usually known to occur following an obstructive pathology. Spontaneous or non-traumatic rupture, in the absence of any distal obstruction, though reported in literature, is not yet a proven entity and needs to be distinguished from physiological forniceal rupture, to validate its occurrence. Our case illustrates that spontaneous ureteric rupture does exist and requires a high level of vigil for prompt diagnosis and early simple management. CASE PRESENTATION: A 65 year old non diabetic gentleman presented with a 2 day history of right sided severe abdominal pain with no history of any prior trauma, surgery, urinary retention or calculus disease. His ultrasound whole-abdomen was suggestive of increased liver echogenicity, but his contrast enhanced CT scan (CECT) documented a ureteric rupture, with leakage of contrast from the upper ureters, well away from the renal pelvis He was promptly managed with cysto-ureteroscopy, retrograde pyelography (RGP) and double-J (DJ) stenting. His post operative course was uneventful and he was discharged on the second post operative day, without event. An RGP at 6 weeks of follow up showed no contrast extravasation from the ureter and his DJ stent was removed without event. CONCLUSION: Spontaneous ureteric rupture, in the absence of any inciting cause, is an entity which exists and is easily manageable, once diagnosed timely. Thus, the need to maintain a high index of vigil, in order to identify this clinically entity at the earnest, institute prompt treatment and hence ensure that a "spontaneous" rupture, doesn't become a "faux pas" in the true sense of the word. PMID- 27388298 TI - [Not Available]. PMID- 27388297 TI - Critical Current Scaling in Long Diffusive Graphene-Based Josephson Junctions. AB - We present transport measurements on long, diffusive, graphene-based Josephson junctions. Several junctions are made on a single-domain crystal of CVD graphene and feature the same contact width of ~9 MUm but vary in length from 400 to 1000 nm. As the carrier density is tuned with the gate voltage, the critical current in these junctions ranges from a few nanoamperes up to more than 5 MUA, while the Thouless energy, ETh, covers almost 2 orders of magnitude. Over much of this range, the product of the critical current and the normal resistance ICRN is found to scale linearly with ETh, as expected from theory. However, the value of the ratio ICRN/ETh is found to be 0.1-0.2, which much smaller than the predicted ~10 for long diffusive SNS junctions. PMID- 27388299 TI - [Not Available]. PMID- 27388300 TI - [Not Available]. PMID- 27388301 TI - [Not Available]. PMID- 27388302 TI - [Not Available]. PMID- 27388303 TI - [Not Available]. PMID- 27388305 TI - [Not Available]. PMID- 27388304 TI - [Not Available]. PMID- 27388306 TI - [Not Available]. PMID- 27388308 TI - [Not Available]. PMID- 27388307 TI - [Not Available]. PMID- 27388309 TI - [Not Available]. PMID- 27388310 TI - [Not Available]. PMID- 27388311 TI - [Not Available]. PMID- 27388312 TI - [Not Available]. PMID- 27388313 TI - [Not Available]. PMID- 27388314 TI - [Not Available]. PMID- 27388315 TI - [Not Available]. PMID- 27388316 TI - [Not Available]. PMID- 27388317 TI - [Not Available]. PMID- 27388318 TI - [Not Available]. PMID- 27388319 TI - [Not Available]. PMID- 27388320 TI - [Not Available]. PMID- 27388322 TI - [Not Available]. PMID- 27388321 TI - [Not Available]. PMID- 27388323 TI - Mass spectrometric properties of N-(2-methoxybenzyl)-2-(2,4,6 trimethoxyphenyl)ethanamine (2,4,6-TMPEA-NBOMe), a new representative of designer drugs of NBOMe series and derivatives thereof. AB - Emergence of new psychoactive substances, hallucinogenic phenethylamines in particular, in illicit market is a serious threat to human health in global scale. We have detected and identified N-(2-methoxybenzyl)-2-(2,4,6 trimethoxyphenyl)ethanamine (2,4,6-TMPEA-NBOMe), a new compound in NBOMe series. Identification was achieved by means of gas chromatography/mass spectrometry (GC/MS), including high-resolution mass spectrometry with tandem experiments (GC/HRMS and GC/HRMS2 ), ultra-high performance liquid chromatography/high resolution mass spectrometry with tandem experiments (UHPLC/HRMS and UHPLC/HRMS2 ), and 1 H and 13 C nuclear magnetic resonance spectroscopy. The peculiarities of fragmentation of the compound under electron ionization (EI) and collision induced dissociation were studied. Despite of the empirical rule denying migration of the hydrogen atom in McLafferty rearrangement to the benzene ring with substituents in the both ortho-positions, it easily occurs for 2,4,6-TMPEA NBOMe in EI conditions. We have noticed that electron-donating substituents, e.g. methoxy groups in the both ortho-positions and para-positions favor the rearrangement. For specially synthesized N-methyl and N-acyl derivatives McLafferty rearrangement is not observed. N-Acyl derivatives demonstrate McLafferty rearrangement, but the charge retains at the alternative fragment involving N-acyl carbonyl group. We have also showed that the hydrogen atoms in 2,4,6-trimethoxybenzene ring may be easily substituted for deuterium or for strong electrophiles like trifluoroacetyl. Analytical characteristics of 2,4,6 TMPEA-NBOMe and of some derivatives thereof which enable their determination in various criminal seizures are given. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388324 TI - Fabrication of naturel pumice/hydroxyapatite composite for biomedical engineering. AB - BACKGROUND: We evaluated the Bovine hydroxyapatite (BHA) structure. BHA powder was admixed with 5 and 10 wt% natural pumice (NP). Compression strength, Vickers micro hardness, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM) and X-ray diffraction studies were performed on the final NP-BHA composite products. The cells proliferation was investigated by MTT assay and SEM. Furthermore, the antimicrobial activity of NP-BHA samples was interrogated. RESULTS: Variances in the sintering temperature (for 5 wt% NP composites) between 1000 and 1300 degrees C, reveal about 700 % increase in the microhardness (~100 and 775 HV, respectively). Composites prepared at 1300 degrees C demonstrate the greatest compression strength with comparable result for 5 wt% NP content (87 MPa), which are significantly better than those for 10 wt% and those that do not include any NP (below 60 MPa, respectively). CONCLUSION: The results suggested the optimal parameters for the preparation of NP-BHA composites with increased mechanical properties and biocompatibility. Changes in micro-hardness and compression strength can be tailored by the tuning the NP concentration and sintering temperature. NP-BHA composites have demonstrated a remarkable potential for biomedical engineering applications such as bone graft and implant. PMID- 27388325 TI - Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report. AB - BACKGROUND: Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug. CASE PRESENTATION: Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity. CONCLUSIONS: Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients. PMID- 27388326 TI - Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens. AB - BACKGROUND: Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. RESULTS: Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. CONCLUSIONS: In conclusion, we have successfully developed a non ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples. PMID- 27388327 TI - Drug Resistance Reversal Potential of Isoliquiritigenin and Liquiritigenin Isolated from Glycyrrhiza glabra Against Methicillin-Resistant Staphylococcus aureus (MRSA). AB - Isoliquiritigenin (ISL) and liquiritigenin (LTG) are structurally related flavonoids found in a variety of plants. Discovery of novel antimicrobial combinations for combating methicillin-resistant Staphylococcus aureus (MRSA) infections is of vital importance in the post-antibiotic era. The present study was taken to explore the in vitro and in vivo combination effect of LTG and ISL with beta-lactam antibiotics (penicillin, ampicillin and oxacillin) against mec A containing strains of MRSA. Minimum inhibitory concentration (MIC) of both LTG and ISL exhibited significant anti-MRSA activity (50-100 ug/mL) against clinical isolates of MRSA. The result of in vitro combination study showed that ISL significantly reduced MIC of beta-lactam antibiotics up to 16-folds [? fractional inhibitory concentration (FIC) 0.312-0.5], while LTG reduced up to 8-folds (?FIC 0.372-0.5). Time kill kinetics at graded MIC combinations (ISL/LTG + beta-lactam) indicated 3.27-9.79-fold and 2.59-3.48-fold reduction in the growth of clinical isolates of S. aureus respectively. In S. aureus-infected Swiss albino mice model, combination of ISL with oxacillin significantly (p < 0.05, p < 0.01, p < 0.001) lowered the systemic microbial burden in blood, liver, kidney, lung and spleen tissues in comparison with ISL, oxacillin alone as well as untreated control. Considering its synergistic antibacterial effect, we suggest both ISL and LTG as promising compounds for the development of novel antistaphylococcal combinations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388328 TI - Temporal Rewiring of Striatal Circuits Initiated by Nicotine. AB - Drug addiction has been conceptualized as maladaptive recruitment of integrative circuits coursing through the striatum, facilitating drug-seeking and drug-taking behavior. The aim of this study was to define temporal neuroadaptations in striatal subregions initiated by 3 weeks of intermittent nicotine exposure followed by protracted abstinence. Enhanced rearing activity was assessed in motor activity boxes as a measurement of behavioral change induced by nicotine (0.36 mg/kg), whereas electrophysiological field potential recordings were performed to evaluate treatment effects on neuronal activity. Dopamine receptor mRNA expression was quantified by qPCR, and nicotine-induced dopamine release was measured in striatal subregions using in vivo microdialysis. Golgi staining was performed to assess nicotine-induced changes in spine density of medium spiny neurons. The data presented here show that a brief period of nicotine exposure followed by abstinence leads to temporal changes in synaptic efficacy, dopamine receptor expression, and spine density in a subregion-specific manner. Nicotine may thus initiate a reorganization of striatal circuits that continues to develop despite protracted abstinence. We also show that the response to nicotine is modulated in previously exposed rats even after 6 months of abstinence. The data presented here suggests that, even though not self-administered, nicotine may produce progressive neuronal alterations in brain regions associated with goal directed and habitual performance, which might contribute to the development of compulsive drug seeking and the increased vulnerability to relapse, which are hallmarks of drug addiction. PMID- 27388329 TI - Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice. AB - Several studies have shown that exercise improves cognitive functions and emotional behaviors. Positive effects of exercise have been associated with enhanced brain plasticity, adult hippocampal neurogenesis, and increased levels of brain-derived neurotrophic factor (BDNF). However, a substantial variability of individual response to exercise has been described, which may be accounted for by individual genetic variants. Here, we have assessed whether and how the common human BDNF Val66Met polymorphism influences the neurobiological effects modulated by exercise in BDNF Val66Met knock-in male mice. Wild-type (BDNFVal/Val) and homozygous BDNF Val66Met (BDNFMet/Met) male mice were housed in cages equipped with or without running wheels for 4 weeks. Changes in behavioral phenotype, hippocampal adult neurogenesis, and gene expression were evaluated in exercised and sedentary control mice. We found that exercise reduced the latency to feed in the novelty suppressed feeding and the immobility time in the forced swimming test in BDNFVal/Val but not in BDNFMet/Met mice. Hippocampal neurogenesis was reduced in BDNFMet/Met mice compared with BDNFVal/Val mice. BDNFMet/Met mice had lower basal BDNF protein levels in the hippocampus, which was not recovered following exercise. Moreover, exercise-induced expression of total BDNF, BDNF splice variants 1, 2, 4, 6 and fibronectin type III domain-containing protein 5 (FNDC5) mRNA levels were absent or reduced in the dentate gyrus of BDNFMet/Met mice. Exercise failed to enhance PGC-1alpha and FNDC5 mRNA levels in the BDNFMet/Met muscle. Overall these results indicate that, in adult male mice, the BDNF Val66Met polymorphism impairs the beneficial behavioral and neuroplasticity effects induced by physical exercise. PMID- 27388332 TI - The MITAT topic issue on TaTME: a window on the possible advances in rectal surgery and medical publishing. PMID- 27388330 TI - Genotype-Dependent Effects of COMT Inhibition on Cognitive Function in a Highly Specific, Novel Mouse Model of Altered COMT Activity. AB - Catechol-O-methyltransferase (COMT) modulates dopamine levels in the prefrontal cortex. The human gene contains a polymorphism (Val158Met) that alters enzyme activity and influences PFC function. It has also been linked with cognition and anxiety, but the findings are mixed. We therefore developed a novel mouse model of altered COMT activity. The human Met allele was introduced into the native mouse COMT gene to produce COMT-Met mice, which were compared with their wild type littermates. The model proved highly specific: COMT-Met mice had reductions in COMT abundance and activity, compared with wild-type mice, explicitly in the absence of off-target changes in the expression of other genes. Despite robust alterations in dopamine metabolism, we found only subtle changes on certain cognitive tasks under baseline conditions (eg, increased spatial novelty preference in COMT-Met mice vs wild-type mice). However, genotype differences emerged after administration of the COMT inhibitor tolcapone: performance of wild type mice, but not COMT-Met mice, was improved on the 5-choice serial reaction time task after tolcapone administration. There were no changes in anxiety related behaviors in the tests that we used. Our findings are convergent with human studies of the Val158Met polymorphism, and suggest that COMT's effects are most prominent when the dopamine system is challenged. Finally, they demonstrate the importance of considering COMT genotype when examining the therapeutic potential of COMT inhibitors. PMID- 27388333 TI - Osteoconduction in keratin-hydroxyapatite composite bone-graft substitutes. AB - Reconstituted keratin-hydroxyapatite (K-HA) composites have shown potential as nonload-bearing bone graft substitute material. This in vivo study investigated the bone regeneration response of keratin plus 40% HA composite materials in comparison to collagen counterparts and an unfilled defect site. The implantation site was a noncritical size defect created in the long bones (tibia) of sheep, with observations made at 1, 2, 4, 6, 8, and 12 weeks postimplantation. Porous K HA materials displayed an excellent biocompatibility similar to collagen counterparts; however, the rate of bone regeneration at K-HA implantation sites was markedly slower than that of the collagen or unfilled defect sites. While collagen materials were undetectable by 4 weeks implantation, K-HA composite remnants were present at 12 weeks. However, there is evidence that K-HA implants participated in the natural remodelling process of bone, with bone regeneration occurring via a creeping substitution mechanism. Observations imply that the rate of bone ingrowth into the K-HA defect site was matched with the rate of K-HA resorption. These results suggest that K-HA materials may offer significant benefits as nonload-bearing bone graft substitutes where it is desirable that the degradation of the scaffolding material be well matched with the rate of bone regeneration. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2034-2044, 2017. PMID- 27388331 TI - T1 and T2 mapping cardiovascular magnetic resonance imaging techniques reveal unapparent myocardial injury in patients with myocarditis. AB - INTRODUCTION: This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance (CMR) to detect myocardial injury in apparently normal myocardium of patients with myocarditis. MATERIALS AND METHODS: We included 20 patients with "infarct-like" acute myocarditis who had typical focal myocardial lesions on late gadolinium enhancement (LGE) images as well as 20 healthy controls. The CMR protocol consisted of a standard myocarditis protocol which was combined with T1 (modified Look-Locker inversion recovery (MOLLI) with a 3(3)5 scheme and T2 mapping (hybrid gradient- and spin-echo multi-echo sequence, GraSE). First, LGE images were used to depict focal myocardial injury and apparently normal, remote myocardium. Second, native T1, T2 and ECV values were obtained in focal lesions but also in apparently normal myocardium. Third, native T1, T2 and ECV values >=2 standard deviations above reference values obtained in healthy volunteers were used to quantify myocardial injury in patients with myocarditis. RESULTS: Apparently normal myocardium had significantly higher median native T1 [1095 (1055-1148) ms] and ECV [34 (32-35) %] values compared to reference values from healthy volunteers, which were 1051 (1021-1064) ms (p < 0.01) and 26 (24-27) % (p < 0.0001). Furthermore, a nonsignificant increase in median myocardial T2 was detected in apparently normal myocardium of patients with myocarditis compared to healthy volunteers [59 (55 65) vs. 56 (54-60) ms; p = 0.18]. Consequently, the amount of myocardial injury was significantly larger on native T1 [48 (32-56) %; p < 0.01] and ECV maps [58 (50-66) %; p < 0.01] compared to LGE [14 (9-20) %]. CONCLUSIONS: Native T1 and ECV maps reveal hidden myocardial injury in normal appearing myocardium of patients with myocarditis. The amount of myocardial injury in myocarditis was underestimated by conventional LGE imaging. PMID- 27388334 TI - Osteogenic and anti-osteoporotic effects of risedronate-added calcium phosphate silicate cement. AB - Osteoporosis greatly impairs bone fracture restoration with bone cement because the accelerated resorption decreases the osseointegration between bone and implants. In this study, we designed a new drug delivery system based on the third generation bisphosphonate risedronate (RA) and the osteogenic calcium phosphate silicate cement (CPSC). The impact of RA on CPSC's material properties and microstructure was evaluated by different characterization methods (MUCT, XRD, FTIR, SEM and gas sorption). In addition, in vitro biocompatibility of RA added CPSC was evaluated (MTT assay, flow cytometry, real-time PCR). In an in vivo study of osteoporotic rabbits, osteoporosis- and bone resorption-related biomarkers were measured over time (ELISA) and local osteogenic and anti osteoporotic effects investigated (x-ray, CT, histology, PCR arrays). RA decreased the setting rate and compressive strength of CPSC by impeding the hydration of calcium silicate. The overall porosity of CPSC was also decreased with RA. The RA-added CPSC was biocompatible and improved osteoblast proliferation and differentiation. The slow release of RA from CPSC reduced the prevalence of osteoporosis in rabbits and improved peri-implant bone formation and osseointegration. In conclusion, RA-containing CPSC demonstrates its potentials to improve fractural restoration under osteoporotic conditions and should be further engineered to increase its effectiveness in fractural restoration. PMID- 27388335 TI - Psychometric properties of the Autism-Spectrum Quotient in both clinical and non clinical samples: Chinese version for mainland China. AB - BACKGROUND: The Autism-Spectrum Quotient (AQ) is widely used to quantify autistic traits, which have been evaluated in the parents of individuals with autism spectrum disorders (ASD) and in the general population. This paper's objective was to investigate the AQ's psychometric properties of the Chinese version for mainland China and to establish whether the pattern of sex differences in the quantity of autistic traits exists. We also examined the usefulness of the AQ in differentiating between individuals with ASD, schizophrenia (SCH), obsessive compulsive disorder (OCD) and healthy controls (HC). METHODS: In this study, the psychometric properties of the AQ were assessed in 1037 parents of children with ASD and in 1040 parents of typically developing children (TDC). Additionally, 32 participants with ASD, 37 patients with SCH, 38 OCD patients and 38 healthy controls (matched for age, gender and IQ) were assessed with the AQ. RESULTS: The internal consistency and test-retest reliability of the AQ and AQ subscales were within an acceptable range. Parents of ASD children scored higher than TDC parents on total AQ and AQ subscales, and TDC parents scored more than parents of ASD children on 2 items of 50. Fathers scored higher than did mothers on total AQ and four subscales, with the sole exception being the subscale attention to detail. The total AQ score of the ASD group was higher than that of the SCH, OCD and HC groups, and the total AQ score of the HC group was significantly lower than that of the SCH and OCD groups, with no differences being observed between the SCH and OCD groups. CONCLUSIONS: The Mandarin AQ demonstrated promising psychometric properties and was a reliable instrument for quantifying autistic traits in both clinical and non-clinical samples in mainland China. PMID- 27388336 TI - The Evolution of Genome Structure by Natural and Sexual Selection. AB - Progress on understanding how genome structure evolves is accelerating with the arrival of new genomic, comparative, and theoretical approaches. This article reviews progress in understanding how chromosome inversions and sex chromosomes evolve, and how their evolution affects species' ecology. Analyses of clines in inversion frequencies in flies and mosquitoes imply strong local adaptation, and roles for both over- and under dominant selection. Those results are consistent with the hypothesis that inversions become established when they capture locally adapted alleles. Inversions can carry alleles that are beneficial to closely related species, causing them to introgress following hybridization. Models show that this "adaptive cassette" scenario can trigger large range expansions, as recently happened in malaria mosquitoes. Sex chromosomes are the most rapidly evolving genome regions of some taxa. Sexually antagonistic selection may be the key force driving transitions of sex determination between different pairs of chromosomes and between XY and ZW systems. Fusions between sex-chromosomes and autosomes most often involve the Y chromosome, a pattern that can be explained if fusions are mildly deleterious and fix by drift. Sexually antagonistic selection is one of several hypotheses to explain the recent discovery that the sex determination system has strong effects on the adult sex ratios of tetrapods. The emerging view of how genome structure evolves invokes a much richer constellation of forces than was envisioned during the Golden Age of research on Drosophila karyotypes. PMID- 27388338 TI - The Metabolic Signature of Biomass Formation in Barley. AB - The network analysis of genome-wide transcriptome responses, metabolic signatures and enzymes' relationship to biomass formation has been studied in a diverse panel of 12 barley accessions during vegetative and reproductive stages. The primary metabolites and enzymes involved in central metabolism that determine the accumulation of shoot biomass at the vegetative stage of barley development are primarily being linked to sucrose accumulation and sucrose synthase activity. Interestingly, the metabolic and enzyme links which are strongly associated with biomass accumulation during reproductive stages are related to starch accumulation and tricarboxylic acid (TCA) cycle intermediates citrate, malate, trans-aconitate and isocitrate. Additional significant associations were also found for UDP glucose, ATP and the amino acids isoleucine, valine, glutamate and histidine during the reproductive stage. A network analysis resulted in a combined identification of metabolite and enzyme signatures indicative for grain weight accumulation that was correlated with the activity of ADP-glucose pyrophosphorylase (AGPase), a rate-limiting enzyme involved in starch biosynthesis, and with that of alanine amino transferase involved in the synthesis of storage proteins. We propose that the mechanism related to vegetative and reproductive biomass formation vs. seed biomass formation is being linked to distinct fluxes regulating sucrose, starch, sugars and amino acids as central resources. These distinct biomarkers can be used to engineer biomass production and grain weight in barley. PMID- 27388337 TI - ANAC032 Positively Regulates Age-Dependent and Stress-Induced Senescence in Arabidopsis thaliana. AB - Members of the NAC transcription factor family have been implicated in the regulation of different processes of plant development including senescence. In this study, the role of ANAC032 is analyzed in Arabidopsis thaliana (Col-0). ANAC032 is shown to act as a transcriptional activator and its expression is induced in senescing leaves as well as in dark-treated detached leaves. Analysis of transgenic overexpressors (OXs) and chimeric repressors (SRDXs) of ANAC032 indicates that ANAC032 positively regulates age-dependent and dark-induced leaf senescence. Quantitative real-time PCR analysis showed that ANAC032 regulates leaf senescence mainly through the modulation of expression of the senescence associated genes AtNYE1, SAG113 and SAUR36/SAG201, which are involved in Chl degradation, and ABA and auxin promotion of senescence, respectively. In addition, ANAC032 expression is induced by a range of oxidative and abiotic stresses. As a result, ANAC032 overexpression lines exhibited enhanced leaf senescence when challenged with different oxidative (3-aminotriazole, fumonisin B1 and high light) and abiotic stress (osmotic and salinity) conditions compared with the wild type. In contrast, ANAC032 SRDX lines displayed the opposite phenotype. ANAC032 transgenic lines showed altered 2,4-D-mediated root tip swelling and root inhibition responses when compared with the wild type. The altered response to auxin, oxidative and abiotic stress treatments in ANAC032 transgenic lines involves differential accumulation of H2O2 compared with the wild type. Taken together, these results indicate that ANAC032 is an important transcription factor that positively regulates age-dependent and stress-induced senescence in A. thaliana by modulating reactive oxygen species production. PMID- 27388339 TI - The SAC51 Family Plays a Central Role in Thermospermine Responses in Arabidopsis. AB - The acaulis5 (acl5) mutant of Arabidopsis thaliana is defective in the biosynthesis of thermospermine and shows a dwarf phenotype associated with excess xylem differentiation. SAC51 was identified from a dominant suppressor of acl5, sac51-d, and encodes a basic helix-loop-helix protein. The sac51-d mutant has a premature termination codon in an upstream open reading frame (uORF) that is conserved among all four members of the SAC51 family, SAC51 and SACL1-SACL3 This suggests that thermospermine cancels the inhibitory effect of the uORF in main ORF translation. Another suppressor, sac57-d, has a mutation in the conserved uORF of SACL3 To define further the function of the SAC51 family in the thermospermine response, we analyzed T-DNA insertion mutants of each gene. Although sacl1-1 may not be a null allele, the quadruple mutant showed a semi dwarf phenotype but with an increased level of thermospermine and decreased sensitivity to exogenous thermospermine that normally represses xylem differentiation. The sac51-1 sacl3-1 double mutant was also insensitive to thermospermine. These results suggest that SAC51 and SACL3 play a key role in thermospermine-dependent negative control of thermospermine biosynthesis and xylem differentiation. Using 5' leader-GUS (beta-glucuronidase) fusion constructs, however, we detected a significant enhancement of the GUS activity by thermospermine only in SAC51 and SACL1 constructs. Furthermore, while acl5-1 sac51-1 showed the acl5 dwarf phenotype, acl5-1 sacl3-1 exhibited an extremely tiny-plant phenotype. These results suggest a complex regulatory network for the thermospermine response in which SAC51 and SACL3 function in parallel pathways. PMID- 27388340 TI - Overexpression of a Novel NAC Domain-Containing Transcription Factor Gene (AaNAC1) Enhances the Content of Artemisinin and Increases Tolerance to Drought and Botrytis cinerea in Artemisia annua. AB - The NAC (NAM, ATAF and CUC) superfamily is one of the largest plant-specific transcription factor families. NAC transcription factors always play important roles in response to various abiotic stresses. A NAC transcription factor gene AaNAC1 containing a complete open reading frame (ORF) of 864 bp was cloned from Artemisia annua. The expression of AaNAC1 could be induced by dehydration, cold, salicylic acid (SA) and methyl jasmonate (MJ), suggesting that it might be a key regulator of stress signaling pathways in A. annua. AaNAC1 was shown to be localized to the nuclei by transforming tobacco leaf epidermal cells. When AaNAC1 was overexpressed in A. annua, the content of artemisinin and dihydroartemisinic acid was increased by 79% and 150%, respectively. The expression levels of artemisinin biosynthetic pathway genes, i.e. amorpha-4,11-diene synthase (ADS), artemisinic aldehyde Delta11(13) reductase (DBR2) and aldehyde dehydrogenase 1 (ALDH1), were increased. Dual luciferase (dual-LUC) assays showed that AaNAC1 could activate the transcription of ADS in vivo. The transgenic A. annua exhibited increased tolerance to drought and resistance to Botrytis cinerea. When AaNAC1 was overexpressed in Arabidopsis, the transgenic Arabidopsis were markedly more tolerant to drought. The transgenic Arabidopsis showed increased resistance to B. cinerea. These results indicate that AaNAC1 can potentially be used in transgenic breeding for improving the content of artemisinin and drought tolerance in A. annua. PMID- 27388341 TI - CyanoP is Involved in the Early Steps of Photosystem II Assembly in the Cyanobacterium Synechocystis sp. PCC 6803. AB - Although the PSII complex is highly conserved in cyanobacteria and chloroplasts, the PsbU and PsbV subunits stabilizing the oxygen-evolving Mn4CaO5 cluster in cyanobacteria are absent in chloroplasts and have been replaced by the PsbP and PsbQ subunits. There is, however, a distant cyanobacterial homolog of PsbP, termed CyanoP, of unknown function. Here we show that CyanoP plays a role in the early stages of PSII biogenesis in Synechocystis sp. PCC 6803. CyanoP is present in the PSII reaction center assembly complex (RCII) lacking both the CP47 and CP43 modules and binds to the smaller D2 module. A small amount of larger PSII core complexes co-purifying with FLAG-tagged CyanoP indicates that CyanoP can accompany PSII on most of its assembly pathway. A role in biogenesis is supported by the accumulation of unassembled D1 precursor and impaired formation of RCII in a mutant lacking CyanoP. Interestingly, the pull-down preparations of CyanoP-FLAG from a strain lacking CP47 also contained PsbO, indicating engagement of this protein with PSII at a much earlier stage in assembly than previously assumed. PMID- 27388342 TI - Ectopic Expression of BnaC.CP20.1 Results in Premature Tapetal Programmed Cell Death in Arabidopsis. AB - Tapetal programmed cell death (PCD) is essential in pollen grain development, and cysteine proteases are ubiquitous enzymes participating in plant PCD. Although the major papain-like cysteine proteases (PLCPs) have been investigated, the exact functions of many PLCPs are still poorly understood in PCD. Here, we identified a PLCP gene, BnaC.CP20.1, which was closely related to XP_013596648.1 from Brassica oleracea. Quantitative real-time PCR analysis revealed that BnaC.CP20.1 expression was down-regulated in male-sterile lines in oilseed rape, suggesting a connection between this gene and male sterility. BnaC.CP20.1 is especially active in the tapetum and microspores in Brassica napus from the uninucleate stage until formation of mature pollen grains during anther development. On expression of BnaC.CP20.1 prior to the tetrad stage, BnA9::BnaC.CP20.1 transgenic lines in Arabidopsis thaliana showed a male-sterile phenotype with shortened siliques containing fewer or no seeds by self-crossing. Scanning electron microscopy indicated that the reticulate exine was defective in aborted microspores. Callose degradation was delayed and microspores were not released from the tetrad in a timely fashion. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay indicated that BnaC.CP20.1 ectopic expression led to premature tapetal PCD. Transmission electron microscopy analyses further demonstrated that the pollen abortion was due to the absence of tectum connections to the bacula in the transgenic anthers. These findings suggest that timely expression of BnaC.CP20.1 is necessary for tapetal degeneration and pollen wall formation. PMID- 27388343 TI - Impact of Sulfur Starvation in Autotrophic and Heterotrophic Cultures of the Extremophilic Microalga Galdieria phlegrea (Cyanidiophyceae). AB - In plants and algae, sulfate assimilation and cysteine synthesis are regulated by sulfur (S) accessibility from the environment. This study reports the effects of S deprivation in autotrophic and heterotrophic cultures of Galdieria phlegrea (Cyanidiophyceae), a unicellular red alga isolated in the Solfatara crater located in Campi Flegrei (Naples, Italy), where H2S is the prevalent form of gaseous S in the fumarolic fluids and S is widespread in the soils near the fumaroles. This is the first report on the effects of S deprivation on a sulfurous microalga that is also able to grow heterotrophically in the dark. The removal of S from the culture medium of illuminated cells caused a decrease in the soluble protein content and a significant decrease in the intracellular levels of glutathione. Cells from heterotrophic cultures of G. phlegrea exhibited high levels of internal proteins and high glutathione content, which did not diminish during S starvation, but rather glutathione significantly increased. The activity of O-acetylserine(thiol)lyase (OASTL), the enzyme synthesizing cysteine, was enhanced under S deprivation in a time-dependent manner in autotrophic but not in heterotrophic cells. Analysis of the transcript abundance of the OASTL gene supports the OASTL activity increase in autotrophic cultures under S deprivation. PMID- 27388344 TI - Use of extensively hydrolysed formula for refeeding neonates postnecrotising enterocolitis: a nationwide survey-based, cross-sectional study. AB - OBJECTIVE: To evaluate the prevalence of and reasons for using extensively hydrolysed formulas (EHFs) of cow's milk proteins in the French neonatal units as well as the modality of their prescription for refeeding infants recovering from necrotising enterocolitis (NEC). METHODS: A multicentre nationwide cross sectional study using a questionnaire to address the prevalence of use and the reasons for prescribing EHF in hospitalised neonates and to examine the protocols and the actual reasons for their use for refeeding infants in recovery from NEC. The questionnaire was sent to only 1 senior neonatologist in each neonatal unit included in the study. RESULTS: More than half of the French neonatal units participated in the survey. 91% of the surveyed units used EHF. Of 1969 infants hospitalised on the day the survey was run, 12% were fed on an EHF. 11% of the EHF prescriptions were due to previous NEC. The main reasons for using an EHF to feed infants post-NEC were the absence of human milk (75%) and surgical management of NEC (17%). When given, EHF was mainly prescribed for a period varying between 15 days and 3 months. None of the involved units continued using the EHF after 6 months of age. More than half of the surveyed units acknowledged hospitalising infants for the initiation of weaning EHF but only 21% of them tested these infants for cow's milk allergy. CONCLUSIONS: The prevalence of EHF use in the French neonatal units is high. Refeeding infants post-NEC is one of the main reasons for such a high prevalence. The main incentive for using an EHF is the absence of human breast milk, either maternal or donor. PMID- 27388346 TI - Correction: Living in Latvia after stroke: the association between functional, social and personal factors and the level of selfperceived disability-a cross sectional study. PMID- 27388345 TI - Multicountry survey of emergency and critical care medicine physicians' fluid resuscitation practices for adult patients with early septic shock. AB - OBJECTIVES: Evidence to guide fluid resuscitation evidence in sepsis continues to evolve. We conducted a multicountry survey of emergency and critical care physicians to describe current stated practice and practice variation related to the quantity, rapidity and type of resuscitation fluid administered in early septic shock to inform the design of future septic shock fluid resuscitation trials. METHODS: Using a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey. RESULTS: A total of 1097 physicians' responses were included. 1 L was the most frequent quantity of resuscitation fluid physicians indicated they would administer at a time (46.9%, n=499). Most (63.0%, n=671) stated that they would administer the fluid challenges as quickly as possible. Overall, normal saline and Ringer's solutions were the preferred crystalloid fluids used 'often' or 'always' in 53.1% (n=556) and 60.5% (n=632) of instances, respectively. However, emergency physicians indicated that they would use normal saline 'often' or 'always' in 83.9% (n=376) of instances, while critical care physicians said that they would use saline 'often' or 'always' in 27.9% (n=150) of instances. Only 1.0% (n=10) of respondents indicated that they would use hydroxyethyl starch 'often' or 'always'; use of 5% (5.6% (n=59)) or 20 25% albumin (1.3% (n=14)) was also infrequent. The majority (88.4%, n=896) of respondents indicated that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct. CONCLUSIONS: Critical care and emergency physicians stated that they rapidly infuse volumes of 500-1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and crystalloids on 90-day mortality in patients with early septic shock. PMID- 27388347 TI - What can we learn on public accountability from non-health disciplines: a meta narrative review. AB - OBJECTIVE: In health, accountability has since long been acknowledged as a central issue, but it remains an elusive concept. The literature on accountability spans various disciplines and research traditions, with differing interpretations. There has been little transfer of ideas and concepts from other disciplines to public health and global health. In the frame of a study of accountability of (international) non-governmental organisations in local health systems, we carried out a meta-narrative review to address this gap. Our research questions were: (1) What are the main approaches to accountability in the selected research traditions? (2) How is accountability defined? (3) Which current accountability approaches are relevant for the organisation and regulation of local health systems and its multiple actors? SETTING: The search covered peer-reviewed journals, monographs and readers published between 1992 and 2012 from political science, public administration, organisational sociology, ethics and development studies. 34 papers were selected and analysed. RESULTS: Our review confirms the wide range of approaches to the conceptualisation of accountability. The definition of accountability used by the authors allows the categorisation of these approaches into four groups: the institutionalist, rights based, individual choice and collective action group. These four approaches can be considered to be complementary. CONCLUSIONS: We argue that in order to effectively achieve public accountability, accountability strategies are to be complementary and synergistic. PMID- 27388348 TI - Bacteraemia predictive factors among general medical inpatients: a retrospective cross-sectional survey in a Japanese university hospital. AB - OBJECTIVES: The precise criteria for obtaining blood cultures have not been established; they depend on the physician's judgement. We examined clinical parameters to determine predictive factors of bacteraemia and the need for blood cultures among general medical inpatients. DESIGN: A retrospective cross sectional survey. SETTING: A Japanese university hospital. PARTICIPANTS: All general inpatients who had blood cultures taken from 1 January 2011 to 31 December 2012. MAIN MEASURES: Clinical information at or just before blood culture sampling was extracted from medical charts. Factors potentially predictive of bacteraemia were analysed using Fisher's exact test, followed by multivariable logistic regression model analysis. MAIN RESULTS: A total of 200 patients (male: female=119:81, 64.3+/-19.1 years old) comprised this study; 57 (28.5%) had positive blood culture results. Multivariable logistic regression analysis revealed that age >60 years (OR=2.75, 95% CI 1.23 to 6.48, p=0.015), female sex (OR=2.21, 95% CI 1.07 to 4.67, p=0.038), pulse rate >90 bpm (OR=5.18, 95% CI 2.25 to 12.48, p<0.001) and neutrophil percentage >80% (OR=3.61, 95% CI 1.71 to 8.00, p=0.001) were independent risk factors for positive blood culture results. The area under the receiver operating characteristic curve analysis of this model was 0.796. CONCLUSIONS: Our results emphasise the importance of taking blood cultures if the pulse rate is >90 bpm, in elderly patients and in women, and for ordering a differential white cell count. PMID- 27388349 TI - Review of 99 self-report measures for assessing well-being in adults: exploring dimensions of well-being and developments over time. AB - OBJECTIVE: Investigators within many disciplines are using measures of well being, but it is not always clear what they are measuring, or which instruments may best meet their objectives. The aims of this review were to: systematically identify well-being instruments, explore the variety of well-being dimensions within instruments and describe how the production of instruments has developed over time. DESIGN: Systematic searches, thematic analysis and narrative synthesis were undertaken. DATA SOURCES: MEDLINE, EMBASE, EconLit, PsycINFO, Cochrane Library and CINAHL from 1993 to 2014 complemented by web searches and expert consultations through 2015. ELIGIBILITY CRITERIA: Instruments were selected for review if they were designed for adults (>=18 years old), generic (ie, non disease or context specific) and available in an English version. RESULTS: A total of 99 measures of well-being were included, and 196 dimensions of well being were identified within them. Dimensions clustered around 6 key thematic domains: mental well-being, social well-being, physical well-being, spiritual well-being, activities and functioning, and personal circumstances. Authors were rarely explicit about how existing theories had influenced the design of their tools; however, the 2 most referenced theories were Diener's model of subjective well-being and the WHO definition of health. The period between 1990 and 1999 produced the greatest number of newly developed well-being instruments (n=27). An illustration of the dimensions identified and the instruments that measure them is provided within a thematic framework of well-being. CONCLUSIONS: This review provides researchers with an organised toolkit of instruments, dimensions and an accompanying glossary. The striking variability between instruments supports the need to pay close attention to what is being assessed under the umbrella of 'well being' measurement. PMID- 27388350 TI - Can smoking initiation contexts predict how adult Aboriginal smokers assess their smoking risks? A cross-sectional study using the 'Smoking Risk Assessment Target'. AB - OBJECTIVES: Smoking prevalence is slow to reduce among Indigenous Australians of reproductive age. We analysed the relationships between age of smoking initiation, recalled initiation influences and self-assessment of smoking risks in Aboriginal smokers. DESIGN, SETTING AND PARTICIPANTS: A community-based cross sectional survey of Aboriginal smokers aged 18-45 years (N=121; 58 men) was undertaken, using single-item measures. The Smoking Risk Assessment Target (SRAT) as the primary outcome measure enabled self-assessment of smoking risks from 12 options, recategorised into 3 groups. Participants recalled influences on their smoking initiation. Multinomial logistic regression modelling included age, gender, strength of urges to smoke, age at initiation (regular uptake) and statistically significant initiation influences on chi(2) tests ('to be cool', alcohol and cannabis). RESULTS: Frequent initiation influences included friends (74%; SD 0.44), family (57%; SD 0.5) and alcohol (40%; SD 0.49). 54% (n=65) of smokers had the highest risk perception on the SRAT, selected by those who cared about the smoking risks and intended to quit soon. On multivariate analyses, compared with the highest level of SRAT, male gender, lower age of uptake and strong urges to smoke were significantly associated with the lowest level of SRAT, selected by those who refuted risks or thought they could not quit. Lower age of uptake and alcohol were associated with mid-level of SRAT, selected by those who cared about smoking risks, but did not consider quitting as a priority. CONCLUSIONS: Characteristics of smoking initiation in youth may have far-reaching associations with how smoking risks are assessed by adults of reproductive age, and their intentions to quit smoking. Becoming a regular smoker at under the age of 16 years, and influences of alcohol on smoking uptake, were inversely associated with high-level assessment of smoking risks and intention to quit in regional Aboriginal smokers. The SRAT may help tailor approaches to Indigenous smoking cessation. PMID- 27388351 TI - Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study. AB - OBJECTIVES: We tested the hypothesis that there is a positive association between maternal body mass index (BMI) and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time. SETTING: Mothers were recruited from the postpartum ward at a university hospital in London. Breast milk samples were collected at the participants' homes. PARTICIPANTS: We recruited 120 healthy, primiparous, breastfeeding mothers, aged over 18 years. Mothers who smoked, had multiple births or had diabetes were excluded. Foremilk and hindmilk samples were collected from 105 women at 1 week postpartum and 92 women at 3 months postpartum. PRIMARY AND SECONDARY OUTCOME MEASURES: We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay. RESULTS: The concentration of leptin in foremilk correlated with maternal BMI at the time of sample collection, at 7 days (r=0.31, p=0.02) and 3 months postpartum (r=0.30, p=<0.00). Foremilk insulin correlated with maternal BMI at 3 months postpartum (r=0.22, p=0.04). Breast milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at 3 months postpartum were increased in foremilk compared with hindmilk (p=0.01). Concentrations of ghrelin were increased in hindmilk collected at 1 week postpartum compared with samples collected at 3 months postpartum (p=0.03). A trend towards decreased insulin concentrations in hindmilk was noted. Concentrations of leptin and resistin were not seen to alter over a feed. CONCLUSIONS: A positive correlation between maternal BMI and foremilk leptin concentration at both time points studied, and foremilk insulin at 3 months postpartum was observed. This may have implications for infant appetite regulation and obesity risk. PMID- 27388352 TI - Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP). AB - INTRODUCTION: In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. METHODS AND ANALYSIS: In this single centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. RESULTS: Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. ETHICS AND DISSEMINATION: The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. TRIAL REGISTRATION NUMBER: NCT02254980. PMID- 27388353 TI - Association of common mental disorder symptoms with health and healthcare factors among women in rural western India: results of a cross-sectional survey. AB - OBJECTIVES: Information about common mental disorders (CMD) is needed to guide policy and clinical interventions in low-income and middle-income countries. This study's purpose was to characterise the association of CMD symptoms with 3 inter related health and healthcare factors among women from rural western India based on a representative, cross-sectional survey. SETTING: Surveys were conducted in the waiting area of various outpatient clinics at a tertiary care hospital and in 16 rural villages in the Anand district of Gujarat, India. PARTICIPANTS: 700 Gujarati-speaking women between the ages of 18-45 years who resided in the Anand district of Gujarat, India, were recruited in a quasi-randomised manner. PRIMARY AND SECONDARY OUTCOMES MEASURES: CMD symptoms, ascertained using WHO's Self Reporting Questionnaire-20 (SRQ-20), were associated with self-reported (1) number of healthcare visits in the prior year; (2) health status and (3) portion of yearly income expended on healthcare. RESULTS: Data from 658 participants were used in this analysis; 19 surveys were excluded due to incompleteness, 18 surveys were excluded because the participants were visiting hospitalised patients and 5 surveys were classified as outliers. Overall, 155 (22.8%) participants screened positive for CMD symptoms (SRQ-20 score >=8) with most (81.9%) not previously diagnosed despite contact with healthcare provider in the prior year. On adjusted analyses, screening positive for CMD symptoms was associated with worse category in self-reported health status (cumulative OR=9.39; 95% CI 5.97 to 14.76), higher portion of household income expended on healthcare (cumulative OR=2.31; 95% CL 1.52 to 3.52) and increased healthcare visits in the prior year (incidence rate ratio=1.24; 95% CI 1.07 to 1.44). CONCLUSIONS: The high prevalence of potential CMD among women in rural India that is unrecognised and associated with adverse health and financial indicators highlights the individual and public health burden of CMD. PMID- 27388354 TI - Prospective assessment of neurodevelopment in children following a pregnancy complicated by severe pre-eclampsia. AB - OBJECTIVE: To prospectively examine whether children of women with a pregnancy affected by severe pre-eclampsia (PE), compared to children of women without a PE affected pregnancy, have differences in neurodevelopmental performance up to 5 years of age. DESIGN: Prospective cohort study. SETTING: Tertiary care centre. PARTICIPANTS: Women were recruited following a PE-affected pregnancy. After each PE participant was recruited, the next normotensive woman without a prior history of PE and matched by parity, maternal age and race was invited to participate. Women with a history of chronic hypertension, diabetes or renal disease were excluded. Total enrolment included 129 PE-affected and 140 normotensive mothers. OUTCOME MEASURES: The primary outcome measure was failure of the Ages and Stages Questionnaire (ASQ). The ASQ was completed yearly, until age 5. RESULTS: A significant difference was found in the proportion of ASQ categories failed in year 3 (p<0.05), and this approached significance in years 1 and 4 (p<0.10 and p<0.15, respectively). At year 1, the number of ASQ categories failed was significantly greater among children born to PE mothers. A subgroup analysis revealed that a significant proportion of PE children born preterm (<37 weeks) failed the ASQ in years 3 and 4 (p<0.05), and when failed, those who were preterm failed significantly more categories (p<0.05). A trend towards increased failure in the gross motor category was found. There was a significant positive correlation between maternal lifetime CVD risk score and number of ASQ categories failed at years 1 and 3 (p<0.05). CONCLUSIONS: Severe PE is associated with other adverse pregnancy outcomes, including intrauterine growth restriction and preterm birth, all of which are associated with increased neurodevelopment delays. Thus, PE indicates a need for early screening and intervention at the neurodevelopmental level to improve children's long-term health, with larger studies required to tease out contributing factors. PMID- 27388355 TI - Understanding recruitment and retention in the NHS community pharmacy stop smoking service: perceptions of smoking cessation advisers. AB - OBJECTIVES: To understand views of pharmacy advisers about smoker recruitment and retention in the National Health Service community pharmacy stop smoking programme. DESIGN: Thematic framework analysis of semistructured, in-depth interviews applying the Theoretical Domains Framework and COM-B behaviour change model. We aimed to identify aspects of adviser behaviour that might be modified to increase numbers joining and completing the programme. PARTICIPANTS: 25 stop smoking advisers (13 pharmacists and 12 support staff). SETTING: 29 community pharmacies in 3 inner east London boroughs. RESULTS: Advisers had preconceived ideas about smokers likely to join or drop out and made judgements about smokers' readiness to quit. Actively recruiting smokers was accorded low priority due in part to perceived insufficient remuneration to the pharmacy and anticipated challenging interactions with smokers. Suggestions to improve smoker recruitment and retention included developing a more holistic and supportive approach using patient-centred communication. Training counter assistants were seen to be important as was flexibility to extend the programme duration to fit better with smokers' needs. CONCLUSIONS: Cessation advisers feel they lack the interpersonal skills necessary to engage well with smokers and help them to quit. Addressing advisers' behaviours about active engagement and follow-up of clients, together with regular skills training including staff not formally trained as cessation advisers, could potentially boost numbers recruited and retained in the stop smoking programme. Adjustments to the pharmacy remuneration structure to incentivise recruitment and to allow personalisation of the programme for individual smokers should also be considered. PMID- 27388356 TI - GPs' perspectives on managing the NHS Health Check in primary care: a qualitative evaluation of implementation in one area of England. AB - OBJECTIVES: To evaluate the implementation of the National Health Service (NHS) Health Check programme in one area of England from the perspective of general practitioners (GPs). DESIGN: A qualitative exploratory study was conducted with GPs and other healthcare professionals involved in delivering the NHS Health Check and with patients. This paper reports the experience of GPs and focuses on the management of the Heath Check programme in primary care. SETTING: Primary care surgeries in the Heart of Birmingham region (now under the auspices of the Birmingham Cross City Clinical Commissioning Group) were invited to take part in the larger scale evaluation. This study focuses on a subset of those surgeries whose GPs were willing to participate. PARTICIPANTS: 9 GPs from different practices volunteered. GPs served an ethnically diverse region with areas of socioeconomic deprivation. Ethnicities of participant GPs included South Asian, South Asian British, white, black British and Chinese. METHODS: Individual semistructured interviews were conducted with GPs face to face or via telephone. Thematic analysis was used to analyse verbatim transcripts. RESULTS: Themes were generated which represent GPs' experiences of managing the NHS Health Check: primary care as a commercial enterprise; 'buy in' to concordance in preventive healthcare; following protocol and support provision. These themes represent the key issues raised by GPs. They reveal variability in the implementation of NHS Health Checks. GPs also need support in allocating resources to the Health Check including training on how to conduct checks in a concordant (or collaborative) way. CONCLUSIONS: The variability observed in this small-scale evaluation corroborates existing findings suggesting a need for more standardisation. Further large-scale research is needed to determine how that could be achieved. Work needs to be done to further develop a concordant approach to lifestyle advice which involves tailored individual goal setting rather than a paternalistic advice-giving model. PMID- 27388357 TI - Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study. AB - INTRODUCTION: Recent research suggests that vitamin D deficiency may cause both bone diseases and a range of non-skeletal diseases. However, most of these data come from observational studies, and clinical trial data on the effects of vitamin D supplementation on individuals with pre-diabetes are scarce and inconsistent. The aim of the Diabetes Prevention with active Vitamin D (DPVD) study is to assess the effect of eldecalcitol, active vitamin D analogue, on the incidence of type 2 diabetes among individuals with pre-diabetes. METHODS AND ANALYSIS: DPVD is an ongoing, prospective, multicentre, randomised, double-blind and placebo-controlled outcome study in individuals with impaired glucose tolerance. Participants, men and women aged >=30 years, will be randomised to receive eldecalcitol or placebo. They will also be given a brief (5-10 min long) talk about appropriate calorie intake from diet and exercise at each 12-week visit. The primary end point is the cumulative incidence of type 2 diabetes. Secondary endpoint is the number of participants who achieve normoglycaemia at 48, 96 and 144 weeks. Follow-up is estimated to span 144 weeks. ETHICS AND DISSEMINATION: All protocols and an informed consent form comply with the Ethics Guideline for Clinical Research (Japan Ministry of Health, Labour and Welfare). The study protocol has been approved by the Institutional Review Board at Kokura Medical Association and University of Occupational and Environmental Health. The study will be implemented in line with the CONSORT statement. TRIAL REGISTRATION NUMBER: UMIN000010758; Pre-results. PMID- 27388358 TI - Potential benefits of healthy food and lifestyle policies for reducing coronary heart disease mortality in Turkish adults by 2025: a modelling study. AB - OBJECTIVE: This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking, physical activity levels, dietary salt, saturated fat intake, mean body mass index (BMI) levels, diabetes prevalence and fruit and vegetable (F&V) consumption on future coronary heart disease (CHD) mortality in Turkey for year 2025. DESIGN: A CHD mortality model previously developed and validated in Turkey was extended to predict potential trends in CHD mortality from 2008 to 2025. SETTING: Using risk factor trends data from recent surveys as a baseline, we modelled alternative evidence-based future risk factor scenarios (modest/ideal scenarios). Probabilistic sensitivity analyses were conducted to account for uncertainties. SUBJECT: Projected populations in 2025 (aged 25-84) of 54 million in Turkey. RESULTS: Assuming lower mortality, modest policy changes in risk factors would result in ~25 635 (range: 20 290-31 125) fewer CHD deaths in the year 2025; 35.6% attributed to reductions in salt consumption, 20.9% to falls in diabetes, 14.6% to declines in saturated fat intake and 13.6% to increase in F&V intake. In the ideal scenario, 45 950 (range: 36 780-55 450) CHD deaths could be prevented in 2025. Again, 33.2% of this would be attributed to reductions in salt reduction, 19.8% to increases in F&V intake, 16.7% to reductions in saturated fat intake and 14.0% to the fall in diabetes prevalence. CONCLUSIONS: Only modest risk factor changes in salt, saturated/unsaturated fats and F&V intake could prevent around 16 000 CHD deaths in the year 2025 in Turkey, even assuming mortality continues to decline. Implementation of population-based, multisectoral interventions to reduce salt and saturated fat consumption and increase F&V consumption should be scaled up in Turkey. PMID- 27388359 TI - Interest and preferences for using advanced physical activity tracking devices: results of a national cross-sectional survey. AB - OBJECTIVES: Pedometers are an effective self-monitoring tool to increase users' physical activity. However, a range of advanced trackers that measure physical activity 24 hours per day have emerged (eg, Fitbit). The current study aims to determine people's current use, interest and preferences for advanced trackers. DESIGN AND PARTICIPANTS: A cross-sectional national telephone survey was conducted in Australia with 1349 respondents. OUTCOME MEASURES: Regression analyses were used to determine whether tracker interest and use, and use of advanced trackers over pedometers is a function of demographics. Preferences for tracker features and reasons for not wanting to wear a tracker are also presented. RESULTS: Over one-third of participants (35%) had used a tracker, and 16% are interested in using one. Multinomial regression (n=1257) revealed that the use of trackers was lower in males (OR=0.48, 95% CI 0.36 to 0.65), non working participants (OR=0.43, 95% CI 0.30 to 0.61), participants with lower education (OR=0.52, 95% CI 0.38 to 0.72) and inactive participants (OR=0.52, 95% CI 0.39 to 0.70). Interest in using a tracker was higher in younger participants (OR=1.73, 95% CI 1.15 to 2.58). The most frequently used tracker was a pedometer (59%). Logistic regression (n=445) revealed that use of advanced trackers compared with pedometers was higher in males (OR=1.67, 95% CI 1.01 to 2.79) and younger participants (OR=2.96, 95% CI 1.71 to 5.13), and lower in inactive participants (OR=0.35, 95% CI 0.19 to 0.63). Over half of current or interested tracker users (53%) prefer to wear it on their wrist, 31% considered counting steps the most important function and 30% regarded accuracy as the most important characteristic. The main reasons for not wanting to use a tracker were, 'I don't think it would help me' (39%), and 'I don't want to increase my activity' (47%). CONCLUSIONS: Activity trackers are a promising tool to engage people in self monitoring a physical activity. Trackers used in physical activity interventions should align with the preferences of target groups, and should be able to be worn on the wrist, measure steps and be accurate. PMID- 27388360 TI - Sociodemographic patterning of long-term diabetes mellitus control following Japan's 3.11 triple disaster: a retrospective cohort study. AB - OBJECTIVE: To assess the sociodemographic patterning of changes in glycaemic control of patients with diabetes affected by the 2011 triple disaster in Japan (earthquake, tsunami and nuclear accident). METHODS: A retrospective cohort study was undertaken with 404 patients with diabetes at a public hospital in Minamisoma City, Fukushima Prefecture. Glycated haemoglobin (HbA1c) levels were measured in 2010, 2011 and 2012 to capture changes in glycaemic control postdisaster. Age, sex, urban/rural residency, evacuation status and medication use were also assessed. RESULTS: There was an overall deterioration in glycaemic control after the disaster, with the mean HbA1c rising from 6.77% in 2010 to 6.90% in 2012 (National Glycohemoglobin Standardization Program, NGSP). Rural residency was associated with a lower likelihood of deteriorating control (OR 0.34, 95% CI 0.13 to 0.84), compared with urban residency. Older age (OR 0.95, 95% CI 0.91 to 0.98) was also slightly protective against increased HbA1c. Evacuation and sex were not significant predictors. CONCLUSIONS: Patients with diabetes who were affected by Japan's triple disaster experienced a deterioration in their glycaemic control following the disasters. The extent of this deterioration was mediated by sociodemographic factors, with rural residence and older age protective against the effects of the disaster on glycaemic control. These results may be indicative of underlying social determinants of health in rural Japan. PMID- 27388361 TI - Protocol for a randomised controlled trial comparing aqueous with alcoholic chlorhexidine antisepsis for the prevention of superficial surgical site infection after minor surgery in general practice: the AVALANCHE trial. AB - INTRODUCTION: Surgical site infection (SSI) after minor skin excisions has a significant impact on patient morbidity and healthcare resources. Skin antisepsis prior to surgical incision is used to prevent SSI, and is performed routinely worldwide. However, in spite of the routine use of skin antisepsis, there is no consensus regarding which antiseptic agents are most effective. The AVALANCHE trial will compare Aqueous Versus Alcoholic Antisepsis with Chlorhexidine for Skin Excisions. METHODS AND ANALYSIS: The study design is a prospective, randomised controlled trial (RCT) with the aim of investigating the impact of two different antiseptic preparations on the incidence of superficial SSI in patients undergoing minor skin excisions. The intervention of 0.5% chlorhexidine gluconate (CHG) in 70% alcohol will be compared with that of 0.5% CHG in aqueous solution. The trial will be conducted in four Australian general practices over a 9-month period, with 920 participants to be recruited. Consecutive patients presenting for minor skin excisions will be eligible to participate. Randomisation will be on the level of the patient. The primary outcome is superficial SSI in the first 30 days following the excision. Secondary outcomes will be adverse effects, including anaphylaxis, skin irritation, contact dermatitis and rash and patterns of antibiotic resistance. ETHICS AND DISSEMINATION: The study has been approved by the James Cook University Human Research Ethics Committee (HREC). Findings will be disseminated in conference presentations and journals and through online electronic media. DISCUSSION: RCTs conducted in general practice differ from hospital-based projects in terms of feasibility, pragmatism and funding. The success of this trial will be cemented in the fact that the research question was established by a group of general practitioners who identified an interesting question which is relevant to their clinical practice and not answered by current evidence. TRIAL REGISTRATION NUMBER: ACTRN12615001045505; Pre-results. PMID- 27388363 TI - Epidemiological impact of achieving UNAIDS 90-90-90 targets for HIV care in India: a modelling study. AB - OBJECTIVE: Recent UNAIDS '90-90-90' targets propose that to end the HIV epidemic by 2030, 90% of persons living with HIV (PLWH) worldwide should know their diagnosis, 90% of diagnosed PLWH should be on antiretroviral therapy (ART) and 90% of PLWH on ART should be virally suppressed by 2020. We sought to quantify the epidemiological impact of achieving these targets in India. METHODS: We constructed a dynamic-transmission model of the Indian HIV epidemic to project HIV infections and AIDS-related deaths that would occur in India over 15 years. We considered several scenarios: continuation of current care engagement (with early ART initiation), achieving 90-90-90 targets on time and delaying achievement by 5 or 10 years. RESULTS: In the base case, assuming continuation of current care engagement, we project 794 000 (95% uncertainty range (UR) 571 000-1 104 000) HIV infections and 689 000 (95% UR 468 000-976 000) AIDS-related deaths in India over 15 years. In this scenario, nearly half of PLWH diagnosed would fail to achieve viral suppression by 2030. With achievement of 90-90-90 targets, India could avert 392 000 (95% UR 248 000-559 000) transmissions (48% reduction) and 414 000 (95% UR 260 000-598 000) AIDS-related deaths (59% reduction) compared to the base-case scenario. Furthermore, fewer than 20 000 (95% UR 12 000-30 000) HIV infections would occur in 2030. Delaying achievement of targets resulted in a similar reduction in HIV incidence by 2030 but at the cost of excess overall infections and mortality. CONCLUSIONS: India can halve the epidemiological burden of HIV over 15 years with achievement of the UNAIDS 90-90-90 targets. Reaching the targets on time will require comprehensive healthcare strengthening, especially in early diagnosis and treatment, expanded access to second-line and third-line ART and long-term retention in care. PMID- 27388362 TI - Mood disturbance and depression in Arab women following hospitalisation from acute cardiac conditions: a cross-sectional study from Qatar. AB - OBJECTIVES: Depression is associated with increased morbidity and mortality rates among cardiovascular patients. Depressed patients have three times higher risk of death than those who are not. We sought to determine the presence of depressive symptoms, and whether gender and age are associated with depression among Arab patients hospitalised with cardiac conditions in a Middle Eastern country. SETTING: Using a non-probability convenient sampling technique, a cross-sectional survey was conducted with 1000 Arab patients >=20 years who were admitted to cardiology units between 2013 and 2014 at the Heart Hospital in Qatar. Patients were interviewed 3 days after admission following the cardiac event. Surveys included demographic and clinical characteristics, and the Arabic version of the Beck Depression Inventory Second Edition (BDI-II). Depression was assessed by BDI II clinical classification scale. RESULTS: 15% of the patients had mild mood disturbance and 5% had symptoms of clinical depression. Twice as many females than males suffered from mild mood disturbance and clinical depression symptoms, the majority of females were in the age group 50 years and above, whereas males were in the age group 40-49 years. chi(2) Tests and multivariate logistic regression analyses indicated that gender and age were statistically significantly related to depression (p<0.001 for all). CONCLUSIONS: Older Arab women are more likely to develop mood disturbance and depression after being hospitalised with acute cardiac condition. Gender and age differences approach, and routine screening for depression should be conducted with all cardiovascular patients, especially for females in the older age groups. Mental health counselling should be available for all cardiovascular patients who exhibit depressive symptoms. PMID- 27388365 TI - Oral health and ventilator-associated pneumonia among critically ill patients: a prospective study. AB - OBJECTIVE: To evaluate the association between oral health and ventilator associated pneumonia (VAP) among critically ill patients. METHODS: A prospective cohort study was conducted among 162 critically ill patients newly intubated and treated with mechanical ventilator in one tertiary hospital in Thailand. Oral health status was assessed using Oral Health Assessment Tool (OHAT), Plaque Index (PI), and number of teeth. VAP, defined as Clinical Pulmonary Infection Score >6, was assessed on Day 4 after intubation. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression adjusted for confounders. RESULTS: Critically ill patients had deteriorating oral health status after intubation. Early-onset VAP developed in 69 patients (42.6%), with VAP incidence of 117 episodes per 1000 ventilator-days. Moderately unhealthy and unhealthy oral conditions based on OHAT scores were associated with a 2.92 fold (95% CI: 1.26-6.74) and 3.22-fold (95% CI: 1.34-7.76) increased risk of VAP. Patients with moderate-to-very poor oral hygiene assessed by PI had increased VAP risk of 1.66-folds (95% CI: 1.001-2.75). The number of teeth was not associated with VAP development. CONCLUSIONS: There is a strong association between poor oral health and increased risk for early-onset VAP. Routine oral care possibly prevents VAP development among critically ill patients treated with mechanical ventilator. PMID- 27388364 TI - Low-glycaemic index diet to improve glycaemic control and cardiovascular disease in type 2 diabetes: design and methods for a randomised, controlled, clinical trial. AB - INTRODUCTION: Type 2 diabetes (T2DM) produces macrovascular and microvascular damage, significantly increasing the risk of cardiovascular disease (CVD), renal failure and blindness. As rates of T2DM rise, the need for effective dietary and other lifestyle changes to improve diabetes management become more urgent. Low glycaemic index (GI) diets may improve glycaemic control in diabetes in the short term; however, there is a lack of evidence on the long-term adherence to low-GI diets, as well as on the association with surrogate markers of CVD beyond traditional risk factors. Recently, advances have been made in measures of subclinical arterial disease through the use of MRI, which, along with standard measures from carotid ultrasound (CUS) scanning, have been associated with CVD events. We therefore designed a randomised, controlled, clinical trial to assess whether low-GI dietary advice can significantly improve surrogate markers of CVD and long-term glycaemic control in T2DM. METHODS AND ANALYSIS: 169 otherwise healthy individuals with T2DM were recruited to receive intensive counselling on a low-GI or high-cereal fibre diet for 3 years. To assess macrovascular disease, MRI and CUS are used, and to assess microvascular disease, retinal photography and 24-hour urinary collections are taken at baseline and years 1 and 3. Risk factors for CVD are assessed every 3 months. ETHICS AND DISSEMINATION: The study protocol and consent form have been approved by the research ethics board of St. Michael's Hospital. If the study shows a benefit, these data will support the use of low-GI and/or high-fibre foods in the management of T2DM and its complications. TRIAL REGISTRATION NUMBER: NCT01063374; Pre-results. PMID- 27388366 TI - Molecular insights into chronotype and time-of-day effects on decision-making. AB - Recent reports highlight that human decision-making is influenced by the time of day and whether one is a morning or evening person (i.e., chronotype). Here, we test whether these behavioral effects are associated with endogenous biological rhythms. We asked participants to complete two well-established decision-making tasks in the morning or evening: the matrix task (an ethical decision task) and the balloon analog risk task (BART; a risk-taking task), and we measured their chronotype in two ways. First, participants completed a self-report measure, the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). Second, we measured the expression of two circadian clock-regulated genes-Per3 and Nr1d2-from peripheral clock cells in participants' hair follicle samples. Using a cosinor model, we estimated the phase of the peripheral clock and assigned RNA chronotypes to participants with advanced (larks) or delayed (owls) phases. The behavioral data were analyzed independently for self-reported (MEQ) and RNA-based chronotypes. We find that significant chronotype and/or time-of-day effects between larks and owls in decision-making tasks occur only in RNA-based chronotypes. Our results provide evidence that time-of-day effects on decision making can be explained by phase differences in oscillating clock genes and suggest that variation in the molecular clockwork may influence inter-individual differences in decision-making behavior. PMID- 27388367 TI - Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats. AB - BACKGROUND: Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition. METHODS: Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays. RESULTS: Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste. CONCLUSION: Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats. PMID- 27388368 TI - Bacteria and Archaea diversity within the hot springs of Lake Magadi and Little Magadi in Kenya. AB - BACKGROUND: Lake Magadi and little Magadi are hypersaline, alkaline lakes situated in the southern part of Kenyan Rift Valley. Solutes are supplied mainly by a series of alkaline hot springs with temperatures as high as 86 degrees C. Previous culture-dependent and culture-independent studies have revealed diverse groups of microorganisms thriving under these conditions. Previous culture independent studies were based on the analysis of 16S rDNA but were done on less saline lakes. For the first time, this study combined illumina sequencing and analysis of amplicons of both total community rDNA and 16S rRNA cDNA to determine the diversity and community structure of bacteria and archaea within 3 hot springs of L. Magadi and little Magadi. METHODS: Water, wet sediments and microbial mats were collected from springs in the main lake at a temperature of 45.1 degrees C and from Little Magadi "Nasikie eng'ida" (temperature of 81 degrees C and 83.6 degrees C). Total community DNA and RNA were extracted from samples using phenol-chloroform and Trizol RNA extraction protocols respectively. The 16S rRNA gene variable region (V4 - V7) of the extracted DNA and RNA were amplified and library construction performed following Illumina sequencing protocol. Sequences were analyzed done using QIIME while calculation of Bray Curtis dissimilarities between datasets, hierarchical clustering, Non Metric Dimensional Scaling (NMDS) redundancy analysis (RDA) and diversity indices were carried out using the R programming language and the Vegan package. RESULTS: Three thousand four hundred twenty-six and one thousand nine hundred thirteen OTUs were recovered from 16S rDNA and 16S rRNA cDNA respectively. Uncultured diversity accounted for 89.35 % 16S rDNA and 87.61 % 16S rRNA cDNA reads. The most abundant phyla in both the 16S rDNA and 16S rRNA cDNA datasets included: Proteobacteria (8.33-50 %), Firmicutes 3.52-28.92 %, Bacteroidetes (3.45-26.44 %), Actinobacteria (0.98-28.57 %) and Euryarchaeota (3.55-34.48 %) in all samples. NMDS analyses of taxonomic composition clustered the taxa into three groups according to sample types (i.e. wet sediments, mats and water samples) with evident overlap of clusters between wet sediments and microbial mats from the three sample types in both DNA and cDNA datasets. The hot spring (45.1 degrees C) contained less diverse populations compared to those in Little Magadi (81-83 degrees C). CONCLUSION: There were significant differences in microbial community structure at 95 % level of confidence for both total diversity (P value, 0.009) based on 16S rDNA analysis and active microbial diversity (P value, 0.01) based on 16S rRNA cDNA analysis, within the three hot springs. Differences in microbial composition and structure were observed as a function of sample type and temperature, with wet sediments harboring the highest diversity. PMID- 27388369 TI - Genetic characterization of feline bocavirus detected in cats in Japan. AB - Feline bocavirus (FBoV) has been classified into three genotypes (FBoV1-FBoV3). FBoVs are mainly detected in feces. In the present study, we collected rectal swabs from cats in Japan and examined the samples for the presence of FBoV. The FBoV infection rate was 9.9 % in 101 cats. No significant association was observed between FBoV infection and clinical symptoms. Based on the full-length NS1 protein, the three strains of FBoVs detected in the present study shared high homologies with the genotype 2 FBoV POR1 strain. This is the first study to report FBoV in Japan. PMID- 27388370 TI - The phylogenetic and recombinational analysis of beak and feather disease virus Taiwan isolates. AB - Beak and feather disease virus (BFDV) is an avian circovirus, and it has a single stranded DNA genome. It causes a fatal disease in parrots called psittacine beak and feather disease (PBFD). After screening of samples collected from Taiwan using PCR, complete genome sequences of isolates from 21 samples from various species of parrot were obtained. The nucleotide sequences of the replication associated protein gene (rep) and the amino acid sequences of the replication associated protein (Rep) were more conserved than the nucleotide sequences of the capsid protein gene (cp) and the amino acid sequences of the capsid protein (CP). In Bayesian phylogenetic analysis, the topology of the complete genome sequence was similar to that of the rep gene alone. Recombination events were identified in Taiwan isolates. Recombination hot spots were mainly located in the intergenic region between the 3' ends of the rep and cp genes and at the 5' end of the cp gene. The 5' end and the middle of the rep gene were found to be recombination cold spots. Despite the overall negative selection that was observed for the rep and cp genes, one and 18 positive selected sites were found for the rep and cp gene, respectively. PMID- 27388371 TI - Foetal death in naive heifers inoculated with Neospora caninum isolate Nc-Spain7 at 110 days of pregnancy. AB - Neospora caninum infection is a leading cause of abortion in cattle worldwide. The pathogenesis of bovine neosporosis, particularly during the second term of gestation when most abortions occur in naturally infected dams, is poorly understood. In the present study foetal death was observed in 3 of 6 experimentally infected dams at 110 days of gestation after 6 weeks of experimental period. All experimental heifers were febrile between 3 and 5 days post infection (dpi). Inoculated dams seroconverted by 3-4 weeks post-infection with higher mean antibody titres in aborting dams compared to non-aborting heifers, although not significantly (p > 0.05). Neospora caninum DNA was detected in all infected foetuses and placentas, and three infected foetuses also had N. caninum antibodies. The parasite burden was higher in the brain of dead/aborted foetuses than in live foetuses. Interestingly, high IFN-gamma production was detected in foetal fluids of a dead foetus found upon euthanasia of its dam, while no IFN-gamma was observed in amniotic, allantoic and/or foetal fluids in the three infected foetuses that were alive upon maternal euthanasia. The present study confirms that the infection of dams on gestation day 110 with 10(7) tachyzoites of the Nc-Spain7 isolate causes abortion. The fact that some infected dams aborted and some did not is relevant to the understanding of N. caninum pathogenesis of abortion in naturally infected cows. PMID- 27388372 TI - EPIDEMIOLOGY Announces the "Validation Study" Submission Category. PMID- 27388373 TI - Cost-effectiveness of preventive case management for parents with a mental illness: a randomized controlled trial from three economic perspectives. AB - BACKGROUND: The children of parents with a mental illness (COPMI) are at increased risk for developing costly psychiatric disorders because of multiple risk factors which threaten parenting quality and thereby child development. Preventive basic care management (PBCM) is an intervention aimed at reducing risk factors and addressing the needs of COPMI-families in different domains. The intervention may lead to financial consequences in the healthcare sector and in other sectors, also known as inter-sectoral costs and benefits (ICBs). The objective of this study was to assess the cost-effectiveness of PBCM from three perspectives: a narrow healthcare perspective, a social care perspective (including childcare costs) and a broad societal perspective (including all ICBs). METHODS: Effects on parenting quality (as measured by the HOME) and costs during an 18-month period were studied in in a randomized controlled trial. Families received PBCM (n = 49) or care as usual (CAU) (n = 50). For all three perspectives, incremental cost-effectiveness ratios (ICERs) were calculated. Stochastic uncertainty in the data was dealt with using non-parametric bootstraps. Sensitivity analyses included calculating ICERs excluding cost outliers, and making an adjustment for baseline cost differences. RESULTS: Parenting quality improved in the PBCM group and declined in the CAU group, and PBCM was shown to be more costly than CAU. ICERs differ from 461 Euros (healthcare perspective) to 215 Euros (social care perspective) to 175 Euros (societal perspective) per one point improvement on the HOME T-score. The results of the sensitivity analyses, based on complete cases and excluding cost outliers, support the finding that the ICER is lower when adopting a broader perspective. The subgroup analysis and the analysis with baseline adjustments resulted in higher ICERs. CONCLUSIONS: This study is the first economic evaluation of family focused preventive basic care management for COPMI in psychiatric and family services. The effects of the chosen perspective on determining the cost effectiveness of PBCM underscore the importance of economic studies of interdepartmental policies. Future studies focusing on the cost-effectiveness of programs like PBCM in other sites and studies with more power are encouraged as this may improve the quality of information used in supporting decision making. TRIAL REGISTRATION: NTR2569 , date of registration 2010-10-12. PMID- 27388374 TI - Development of an accreditation scheme by the Royal College of Anaesthetists. PMID- 27388375 TI - The use of freedom of information requests in medical audit and research. PMID- 27388377 TI - Is modern management of fistula-in-ano acceptable? AB - Fistula-in-ano has been managed by a number of techniques and there remains no consensus on the most appropriate management for all patients. The mainstay of any treatment balances the need to control sepsis vs the risk of potential incontinence post-intervention. Management should focus on the primary source of sepsis. PMID- 27388378 TI - Transanal endoscopic surgery: past, present and future. AB - Transanal endoscopic surgery is a safe, established technique to remove lesions in the rectum via the anus. This article reviews its evolution, approaches, indications and evidence for its role in treating benign rectal polyps. The future of transanal endoscopic surgery in rectal cancer and inflammatory bowel disease is also explored. PMID- 27388379 TI - Digital clubbing: forms, associations and pathophysiology. AB - Among proposed mechanisms to explain digital clubbing, the release of cytokines, specifically vascular endothelial growth factor and platelet-derived growth factor, from aggregated platelets and megakaryocytes has emerged as the most likely explanation. This review describes these and other contributory processes. PMID- 27388380 TI - Eosinophilic oesophagitis. AB - Eosinophilic oesophagitis is a chronic immune-mediated inflammatory disorder of the oesophagus, characterized by symptoms of dysphagia or food bolus obstruction. Diagnosis is supported by typical histological findings. This article covers pertinent aspects of the disease, pathogenic explanations and treatment options. PMID- 27388381 TI - Gaining approval for clinical research. AB - Set-up and delivery of a clinical research project can be complicated and difficult. This article introduces the regulatory processes involved in gaining approval for clinical research and discusses the obstacles that may be encountered. PMID- 27388382 TI - Female genital mutilation and reporting duties for all clinical personnel. AB - Female genital mutilation is illegal. It is now mandatory for health-care professionals to report female genital mutilation to the police. Professionals caring for women and girls of all ages must understand how female genital mutilation presents, and what action to take. PMID- 27388383 TI - Work-based assessments through the eyes of a core surgical trainee. PMID- 27388384 TI - William Barnsley Allen: a medical hero of the Battle of the Somme. PMID- 27388385 TI - Atypical and disseminated herpes zoster. PMID- 27388386 TI - Exercise-induced erythema nodosum. PMID- 27388387 TI - Furosemide-induced eruption of haemorrhagic bullae on the fingers. PMID- 27388388 TI - Did someone say 'short of breath'? PMID- 27388389 TI - Core surgical training: addressing the inbetweener effect. PMID- 27388391 TI - Video laryngoscopes for all? PMID- 27388392 TI - Psoriatic arthritis. PMID- 27388393 TI - An approach to joint pain and inflammatory arthropathies. PMID- 27388394 TI - Enzyme-linked immunosorbent assay (ELISA): the basics. PMID- 27388395 TI - Burnout Syndrome in the Intensive Care Unit. Future Directions for Research. PMID- 27388396 TI - Chronic Bronchitis in Chronic Obstructive Pulmonary Disease. Magnifying Why Smoking Cessation Still Matters Most. PMID- 27388397 TI - Living with Interstitial Lung Disease: How Do We Best Meet the Educational Needs of Our Patients? PMID- 27388398 TI - Diagnoses (Not Diagnosis) of Pleural Effusion. Time to Consider Concurrent Etiologies. PMID- 27388399 TI - Noninvasive Ventilation for Acute Asthma. "Spill-over" or "Lighted Windows"? PMID- 27388400 TI - Exploring Providers' Perspectives on Early Decisions to Withdraw Life-Sustaining Therapy after Cardiac Arrest. One Side of the Story. PMID- 27388401 TI - Unreliable Syndromes, Unreliable Studies. PMID- 27388402 TI - Is Hyperinflation from Chronic Obstructive Pulmonary Disease "Protective" of Upper Airway Collapse in Obstructive Sleep Apnea? PMID- 27388403 TI - The Cystic Fibrosis Foundation Patient Registry. Design and Methods of a National Observational Disease Registry. PMID- 27388405 TI - Pediatric Chronic Home Invasive Ventilation. PMID- 27388406 TI - A Subsolid Pulmonary Lesion. Diagnostic Considerations and Management Options. PMID- 27388404 TI - ATS Core Curriculum 2016. Part IV. Adult Pulmonary Medicine Core Curriculum. PMID- 27388407 TI - Impaired Respiratory Function in Chronic Thromboembolic Pulmonary Hypertension: A Comparative Study with Healthy Control Subjects. PMID- 27388408 TI - Recurrent Tracheal Stenosis: A Novel Presentation of Silicosis. PMID- 27388409 TI - Cumulative Faults with Serial Testing for Latent Tuberculosis in Low-Risk Populations. PMID- 27388410 TI - Finding Truth in Biased Results. PMID- 27388411 TI - Interpreting False Positive Tuberculosis Tests in Occupational Screening: The Fault of the Test, the Testing Schedule, or Both? PMID- 27388412 TI - Reply: Interpreting False Positive Tuberculosis Tests in Occupational Screening: The Fault of the Test, the Testing Schedule, or Both? PMID- 27388413 TI - Asthma/COPD Overlap Syndrome and Medicare 30-Day Readmissions. PMID- 27388414 TI - Reply: Asthma/COPD Overlap Syndrome and Medicare 30-Day Readmissions. PMID- 27388415 TI - Reply: Video Laryngoscopy: Take It to the Floor. PMID- 27388416 TI - Video Laryngoscopy: Take It to the Floor. PMID- 27388417 TI - Femtosecond Excited State Dynamics of Size Selected Neutral Molecular Clusters. AB - The work describes a novel experimental approach to track the relaxation dynamics of an electronically excited distribution of neutral molecular clusters formed in a supersonic expansion, by pump-probe femtosecond ionization. The introduced method overcomes fragmentation issues and makes possible to retrieve the dynamical signature of a particular cluster from each mass channel, by associating it to an IR transition of the targeted structure. We have applied the technique to study the nonadiabatic relaxation of pyrrole homoclusters. The results obtained exciting at 243 nm, near the origin of the bare pyrrole electronic absorption, allow us to identify the dynamical signature of the dimer (Py)2, which exhibits a distinctive lifetime of tau1 ~ 270 fs, considerably longer than the decays recorded for the monomer and bigger size clusters (Py)n>2. A possible relationship between the measured lifetime and the clusters geometries is tentatively discussed. PMID- 27388418 TI - Mn-Promoted Co3O4/TiO2 as an efficient catalyst for catalytic oxidation of dibromomethane (CH2Br2). AB - Brominated hydrocarbon is the typical pollutant in the exhaust gas from the synthesis process of Purified Terephthalic Acid (PTA), which may cause various environmental problems once emitted into atmosphere. Dibromomethane (DBM) was employed as the model compound in this study, and a series of TiO2-supported manganese and cobalt oxide catalysts with different Mn/Co molar ratio were prepared by the impregnation method and used for catalytic oxidation of DBM. It was found that the addition of Mn significantly enhanced the catalytic performance of Co/TiO2 catalyst. Among all the prepared catalysts, Mn(1)-Co/TiO2 (Mn/Co molar ratio was 1) catalyst exhibited the highest activity with T90 at about 325 degrees C and good stability maintained for at least 30h at 500ppm DBM and 10% O2 at GHSV=60,000h(-1), and the final products in the reaction were COx, HBr and Br2, without the formation of Br-containing organics. The high activity and high stability might be attributed to the redox cycle (Co(2+)+Mn(4+)< >Co(3+)+Mn(3+)) over Mn-promoted Co3O4/TiO2 catalyst. Based on the results of in situ DRIFT studies and analysis of products, a plausible reaction mechanism for catalytic oxidation of DBM over Mn-Co/TiO2 catalysts was also proposed. PMID- 27388419 TI - Microbial fuel cell driving electrokinetic remediation of toxic metal contaminated soils. AB - An investigation of the feasibility of in-situ electrokinetic remediation for toxic metal contaminated soil driven by microbial fuel cell (MFC) is presented. Results revealed that the weak electricity generated from MFC could power the electrokinetic remediation effectively. The metal removal efficiency and its influence on soil physiological properties were also investigated. With the electricity generated through the oxidation of organics in soils by microorganisms, the metals in the soils would mitigate from the anode to the cathode. The concentrations of Cd and Pb in the soils increased gradually through the anode to the cathode regions after remediation. After about 143days and 108 days' operation, the removal efficiencies of 31.0% and 44.1% for Cd and Pb at the anode region could be achieved, respectively. Soil properties such as pH and soil conductivity were also significantly redistributed from the anode to the cathode regions. The study shows that the MFC driving electrokinetic remediation technology is cost-effective and environmental friendly, with a promising application in soil remediation. PMID- 27388420 TI - Rapid removal of bacterial endotoxin and natural organic matter in water by dielectric barrier discharge plasma: Efficiency and toxicity assessment. AB - Low-temperature plasma was used to control bacteria, endotoxins and natural organic matter (NOM) in water by a dielectric barrier discharge (DBD) device. Results indicate that DBD plasma has an obvious inactivation effect on various bacteria in water. The degree of inactivation from difficult to easy is as follows: Bacillus subtilis>Escherichia coli>Staphylococcus aureus. Activated ultrapure water treated using DBD plasma exhibited a sustained sterilization effect, but this sterilization effect decreased gradually after 1h. The total endotoxin (free-endotoxin and bound-endotoxin) released by Escherichia coli during inactivation, as well as artificially simulated endotoxin in a control solution, was significantly controlled by DBD plasma. Both the metabolites that appeared after inactivation of microorganisms by plasma treatment, and the NOM in filtration effluent of a water treatment plant were well removed by DBD plasma if the treatment duration was sufficiently long. However, the acute toxicity increased significantly, and persisted for at least 2h, indicating that some long life active substances were generated during the DBD process. Therefore, the removal of bacteria, endotoxins or NOM does not mean a safe water is produced. It is also important to eliminate the toxicity and byproducts produced during water treatment for the continuous promotion and industrial application of DBD plasma. PMID- 27388421 TI - Predictors of Outcome in Traumatic Brain Injury: New Insight Using Receiver Operating Curve Indices and Bayesian Network Analysis. AB - BACKGROUND: Traumatic brain injury remains a global health problem. Understanding the relative importance of outcome predictors helps optimize our treatment strategies by informing assessment protocols, clinical decisions and trial designs. In this study we establish importance ranking for outcome predictors based on receiver operating indices to identify key predictors of outcome and create simple predictive models. We then explore the associations between key outcome predictors using Bayesian networks to gain further insight into predictor importance. METHODS: We analyzed the corticosteroid randomization after significant head injury (CRASH) trial database of 10008 patients and included patients for whom demographics, injury characteristics, computer tomography (CT) findings and Glasgow Outcome Scale (GCS) were recorded (total of 13 predictors, which would be available to clinicians within a few hours following the injury in 6945 patients). Predictions of clinical outcome (death or severe disability at 6 months) were performed using logistic regression models with 5-fold cross validation. Predictive performance was measured using standardized partial area (pAUC) under the receiver operating curve (ROC) and we used Delong test for comparisons. Variable importance ranking was based on pAUC targeted at specificity (pAUCSP) and sensitivity (pAUCSE) intervals of 90-100%. Probabilistic associations were depicted using Bayesian networks. RESULTS: Complete AUC analysis showed very good predictive power (AUC = 0.8237, 95% CI: 0.8138-0.8336) for the complete model. Specificity focused importance ranking highlighted age, pupillary, motor responses, obliteration of basal cisterns/3rd ventricle and midline shift. Interestingly when targeting model sensitivity, the highest ranking variables were age, severe extracranial injury, verbal response, hematoma on CT and motor response. Simplified models, which included only these key predictors, had similar performance (pAUCSP = 0.6523, 95% CI: 0.6402-0.6641 and pAUCSE = 0.6332, 95% CI: 0.62-0.6477) compared to the complete models (pAUCSP = 0.6664, 95% CI: 0.6543-0.679, pAUCSE = 0.6436, 95% CI: 0.6289-0.6585, de Long p value 0.1165 and 0.3448 respectively). Bayesian networks showed the predictors that did not feature in the simplified models were associated with those that did. CONCLUSION: We demonstrate that importance based variable selection allows simplified predictive models to be created while maintaining prediction accuracy. Variable selection targeting specificity confirmed key components of clinical assessment in TBI whereas sensitivity based ranking suggested extracranial injury as one of the important predictors. These results help refine our approach to head injury assessment, decision-making and outcome prediction targeted at model sensitivity and specificity. Bayesian networks proved to be a comprehensive tool for depicting probabilistic associations for key predictors giving insight into why the simplified model has maintained accuracy. PMID- 27388422 TI - Alkyl Chain Length Dependence of the Dynamics and Structure in the Ionic Regions of Room-Temperature Ionic Liquids. AB - The dynamics of four 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide room-temperature ionic liquids (RTILs) with carbon chain lengths of 2, 4, 6, and 10 were studied by measuring the orientational and spectral diffusion dynamics of the vibrational probe SeCN(-). Vibrational absorption spectra, two-dimensional infrared (2D IR), and polarization-selective pump-probe (PSPP) experiments were performed on the CN stretch. In addition, optical heterodyne-detected optical Kerr effect (OHD-OKE) experiments were performed on the bulk liquids. The PSPP experiments yielded triexponential anisotropy decays, which were analyzed with the wobbling-in-a-cone model. The slowest decay, the complete orientational randomization, slows with increasing chain length in a hydrodynamic trend consistent with the increasing viscosity. The shortest time scale wobbling motions are insensitive to chain length, while the intermediate time scale wobbling slows mildly as the chain length increases. The 2D IR spectra measured in parallel (?XXXX?) and perpendicular (?XXYY?) polarization configurations gave different decays, showing that reorientation-induced spectral diffusion (RISD) contributes to the dynamics. The spectral diffusion caused by the RTIL structural fluctuations was obtained by removing the RISD contributions. The faster structural fluctuations are relatively insensitive to chain length. The slowest structural fluctuations slow substantially when going from Emim (2 carbon chain) to Bmim (4 carbon chain) and slow further, but more gradually, as the chain length is increased. It was shown previously that K(+) causes local ion clustering in the Emim RTIL. The K(+) effect increases with increasing chain length. The OHD-OKE measured complete structural randomization times slow substantially with increasing chain length and are much slower than the dynamics experienced by the SeCN(-) located in the ionic regions of the RTILs. PMID- 27388423 TI - Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet. AB - OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS. METHODS: The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluorescence activated cell sorting analysis for intracellular cytokines and surface markers. RESULTS: Rectal biopsies from wheat-challenged NCWS patients showed that a significant mucosal CD45(+) infiltrate consisted of CD3(+) and CD3(-) lymphocytes, with the latter spontaneously producing more interferon (IFN)-gamma than IBS controls. About 30% of IFN-gamma-producing CD45(+) cells were T-bet(+), CD56(-), NKP44(-), and CD117(-), defining them as a type-1 innate lymphoid cells (ILC1). IFN-gamma-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet. CONCLUSIONS: These data indicate that, in patients with active NCWS, IFN-gamma-producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cell population in the pathogenesis of NCWS. PMID- 27388424 TI - Successful Treatment of Hepatitis C Virus-associated Oral Lichen Planus by Interferon-free Therapy with Direct-acting Antivirals. AB - OBJECTIVES: Oral lichen planus (OLP) is one of the extrahepatic manifestations of hepatitis C virus (HCV) infection. Presently developed interferon (IFN)-free direct-acting antivirals (DAAs) used to treat HCV infection have low side effect profiles and high efficacy. However, there are no studies examining the relationship between OLP and IFN-free DAAs. The aim of this study was to evaluate the disease course in patients with HCV-associated OLP, who received treatment with IFN-free DAAs. METHODS: Seven patients with HCV-related OLP (including one with cutaneous LP), who received IFN-free treatment with daclatasvir (DCV)/asunaprevir (ASV) at our hospital in Japan from October, 2014 to February, 2015 were enrolled in the study. The subjects included four males and three females (average age, 73.9 years). We compared the symptoms of OLP in the patients before and at 24 weeks after the end of DAA therapy. RESULTS: No worsening of symptoms was observed during treatment with the DAAs. The symptoms of OLP had subsided in all seven patients. Lesions of OLP and cutaneous LP disappeared in four, and improved in three of the seven patients after sustained virological response 24. No systemic clinical adverse events were observed in all patients. CONCLUSIONS: Herein, we have reported the outcomes of HCV-associated OLP in patients who received successful treatment with IFN-free DAAs, using the DCV/ASV combination therapy. PMID- 27388425 TI - Glomerular Filtration Rate Estimation in Renal and Non-Renal Solid Organ Transplantation. AB - Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like hypertension, hypotension, drugs and infections may play a causative role as well. Organ specific causes include hepatorenal syndrome, cirrhosis, low cardiac function, low respiratory function and diabetes developed both before and after TX. It is important to be able to perform precise and valid measurements or estimates of renal function in these patients, in order to accurately and safely dose immunosuppressive medication and perform and adjust the treatment and prophylaxis of renal dysfunction. This is a short overview and discussion of relevant studies and possible caveats of estimated glomerular filtration rate methods for use in renal and non-renal TX. PMID- 27388426 TI - A proposed experimental diagnosing of specular Andreev reflection using the spin orbit interaction. AB - Based on the Dirac-Bogoliubov-de Gennes equation, we theoretically investigate the chirality-resolved transport properties through a superconducting heterojunction in the presence of both the Rashba spin orbit interaction (RSOI) and the Dresselhaus spin orbit interaction (DSOI). Our results show that, if only the RSOI is present, the chirality-resolved Andreev tunneling conductance can be enhanced in the superconducting gap, while it always shows a suppression effect for the case of the DSOI alone. In contrast to the similar dependence of the specular Andreev zero bias tunneling conductance on the SOI, the retro-Andreev zero bias tunneling conductance exhibit the distinct dependence on the RSOI and the DSOI. Moreover, the zero-bias tunneling conductances for the retro-Andreev reflection (RAR) and the specular Andreev reflection (SAR) also show a qualitative difference with respect to the barrier parameters. When the RSOI and the DSOI are finite, three orders of magnitude enhancement of specular Andreev tunneling conductance is revealed. Furthermore, by analyzing the balanced SOI case, we find that the RAR is in favor of a parabolic dispersion, but a linear dispersion is highly desired for the SAR. These results shed light on the diagnosing of the SAR in graphene when subjected to both kinds of SOI. PMID- 27388427 TI - Forensic Spanish allele and haplotype database for a 17 X-STR panel. AB - The currently developed 17 X-STR panel (DXS8378, DXS9898, DXS7133, GATA31E08, GATA172D05, DXS6801, DXS7423, DXS6809, DXS6799, DXS7132, DXS9902, DXS6800, DXS6789, DXS10075, DXS10079, DXS6807, and DXS6803) offers a highly discriminative tool for forensic identification and kinship testing. With the aim of providing a global Spanish population X-STR database, we present haplotype and allele frequencies and parameters of forensic interest for the 17 X-STR panel obtained from 593 unrelated individuals from Alicante, Aragon, the Basque Country, Andalusia, Galicia, Madrid, and Barcelona that represent the most populated regions of the Spanish Peninsular territory. The seven populations were compared to test possible population genetic substructures. The lack of significant differences among the studied Spanish populations supports the use of the allele and haplotype frequency database presented herein as a global Spanish population sample useful for statistical evaluation in forensic casework. After conducting the LD plots derived from HapMap and pairwise linkage disequilibrium tests, DXS7132, DXS10075, and DXS10079 markers were included in a cluster and haplotype frequencies were calculated. The improvement in the forensic parameters for the Spanish population using 17 X-STRs in comparison to the previous 10 X-STR allele frequencies database is also shown. PMID- 27388428 TI - Probabilistically determining the cellular source of DNA derived from differential extractions in sexual assault scenarios. AB - Sexual assault cases are the type of case that often produces questions about the cellular source of DNA. In these cases multiple findings of microscopy, DNA profiling and presumptive testing need to be considered when addressing source level propositions. In this work, I consider a line of questioning that has been raised a number of times in the recent past, where in court it was disputed that low levels of sperm seen on a microscope slide were the cellular source of the male DNA profile component generated from the sperm fraction of a differential DNA extraction. I demonstrate how the cell scoring results and DNA profiling results can be considered together, in helping address this source level question through the use of Bayesian Networks. PMID- 27388429 TI - Evidence to support the hypothesis of tuberculosis as a cause of extreme osteonecrosis and osteomyelitis of the mandible in a West African population. AB - Maxillofacial tuberculosis (TB) is rare. The cases of 19 patients showing extreme bony destruction in the mandible, collected over a 3-month period in West Africa, are presented. Clinical, radiographic, and histological evidence indicated Mycobacterium tuberculosis as a possible cause. Further studies are in progress. PMID- 27388430 TI - Lipid droplets in cultured luteal cells in non-pregnant sheep fed different planes of nutrition. AB - Accumulation of lipid droplets (LD) in luteal cells likely is important for energy storage and steroidogenesis in the highly metabolically active corpus luteum (CL). The objective of this study was to determine the effect of plane of nutrition on progesterone (P4) secretion, and lipid droplet number and size in cultured ovine luteal cells. Ewes were randomly assigned to one of three nutritional groups: control (C; 100% NRC requirements, n=9), overfed (O; 2*C, n=12), or underfed (U; 0.6*C, n=10). Superovulation was induced by follicle stimulating hormone injections. At the early and mid-luteal phases of the estrous cycle, CL were dissected from ovaries, and luteal cells isolated enzymatically. Luteal cells were incubated overnight in medium containing serum in chamber slides. Media were then changed to serum-free and after 24h incubation, media were collected for P4 analysis, and cells were fixed in formalin and stained with BODIPY followed by DAPI staining. Z-stacks of optical sections of large and small luteal cells (LLC and SLC, respectively) were obtained using a laser-scanning microscope. Rendered 3D images of individual LLC and SLC were analyzed for cell volume, and total and individual LD volume, number and percentage of cellular volume occupied by LD by using Imaris software. Concentrations of P4 in serum and media were greater (P<0.05) at the mid than early-luteal phase, and were not affected by nutritional plane. LD total volume and number were greater (P<0.001) in LLC than SLC; however, mean volume of individual LD was greater (P<0.02) in SLC than LLC. In LLC, total LD volume was greater (P<0.02) in O than C and U ewes. In SLC, total LD volume and number was greater (P<0.003) at the mid than early-luteal phase, and percentage of cell volume occupied by LD was greater (P<0.002) in U than C and O ewes. These data demonstrate that both stage of luteal development and nutritional plane affect selected LD measurements and thus may affect luteal functions. Furthermore, these data confirm that LD dynamics differ among parenchymal steroidogenic luteal cell types. PMID- 27388431 TI - Serum and Plasma Levels of Vascular Endothelial Growth Factors in Relation to Quality of Glucose Control, Biomarkers of Inflammation, and Diabetic Nephropathy. AB - Levels of vascular endothelial growth factors (VEGF) are regulated in a complex network of adipokines, glucose control, and low grade inflammation together with activated platelets, leucocytes, and endothelial dysfunction. Increased levels of VEGF are associated with enhanced angiogenesis and impaired repair mechanisms of vascular lesions in endorgans. Little is known about the interaction of systemic VEGF levels with quality of diabetes control, biomarkers of inflammation, and diabetic nephropathy. Moreover, it is unclear, whether serum and plasma VEGF levels are similarly suited to reflect risk associated with VEGF.In this case control study, we analyzed these parameters in serum and plasma of age and sex matched controls without diabetes (n=99) and type 2 diabetes (n=302). Serum VEGF A was significantly increased in patients with T2DM while plasma levels were in the same range as for controls. Individual levels varied in a wide range. Serum levels were 4.9 times higher in controls and 7.3 times higher in T2DM as compared to plasma levels. T2DM was associated with significantly higher levels of hsCRP, ALAT, and albumin/creatinine ratio. When calculated for tertiles of HbA1c, we observed a highly significant increase from tertile one to the upper tertile for serum VEGF-A but not for plasma VEGF-A. Correlation analysis revealed a significant relationship between VEGF-A, HbA1c, inflammation, and diabetic nephropathy. Our results indicate that increased VEGF-A levels in T2DM significantly depend on quality of HbA1c control. Serum levels of VEGF-A, with a strong contribution of platelet derived VEGF, better reflect the glycemic burden than plasma levels of VEGF-A. Mechanistic studies are needed to explore links to inflammation and diabetic nephropathy. PMID- 27388433 TI - Mouse model of primary biliary cholangitis with a striking female predominance: A new powerful research tool. PMID- 27388432 TI - Effect of irrigation on surface roughness and fatigue resistance of controlled memory wire nickel-titanium instruments. AB - AIM: To investigate the effect of irrigation on the surface roughness and fatigue resistance of HyFlex and M3 controlled memory (CM) wire nickel-titanium instruments. METHODOLOGY: Two new files of each brand were analysed by atomic force microscopy (AFM). Then, the instruments were dynamically immersed in either 5.25% sodium hypochlorite (NaOCl) or 17% ethylene diamine tetraacetic acid (EDTA) solution for 10 min, followed by AFM analysis. The roughness average (Ra) and root mean square (RMS) values were analysed statistically using an independent sample t-test. Then, 36 files of each brand were randomly assigned to three groups (n = 12). Group 1 (the control group) was composed of new instruments. Groups 2 and 3 were dynamically immersed in 5.25% NaOCl and 17% EDTA solutions for 10 min, respectively. The number of rotations to failure for various groups was analysed using the one-way analysis of variance software. RESULTS: For M3 files, the Ra and RMS values significantly increased (P < 0.05) after the immersion. For the HyFlex file, the Ra and RMS values significantly increased (P < 0.05) only in EDTA, but not (P > 0.05) NaOCl. The resistance to cyclic fatigue of both HyFlex and M3 files did not significantly decrease (P > 0.05) by immersing in 5.25% NaOCl and 17% EDTA solutions. CONCLUSIONS: Except the HyFlex files immersed in NaOCl, the surface roughness of other files exposed to irrigants increased. However, a change in the surface tomography of CM wire instruments caused by contact with irrigants for 10 min did not trigger a decrease in cyclic fatigue resistance. PMID- 27388434 TI - Notes from the Field: Outbreak of Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 Among Basic Military Trainees - Texas, 2015. AB - On July 7, 2015, a man aged 22 years reported to sick call during basic military training at Lackland Air Force Base (AFB), Texas. He had erythematous, crusted papulovesicular lesions on the extensor surfaces of the upper and lower extremities. The patient was afebrile and otherwise well, and was evaluated later that day by the dermatology service. A viral infection was considered most likely because of the patient's age, absence of fever or constitutional symptoms, and the distribution and morphology of the lesions. The initial differential diagnosis included Henoch-Schonlein purpura, parvovirus B19, and Rocky Mountain spotted fever. However, the clinical signs, including the unique morphology and distribution of grouped vesicles and papules was suggestive of hand, foot, and mouth disease (HFMD), although the patient did not have oral lesions and reported no contact with another person with HFMD. A viral culture and punch biopsy of one of the lesions were obtained. PMID- 27388435 TI - Effect of lavender aromatherapy on menopause hot flushing: A crossover randomized clinical trial. AB - BACKGROUND: Flushing is generally considered to be the primary symptom of menopause and is typically the most common complaint in menopausal women. Although flushing poses no danger to a woman's health, it decreases the quality of life. Thus, the purpose of this study was to determine the effect of lavender aromatherapy on menopause flushing. METHODS: This double-blinded crossover clinical trial included 100 menopausal women 45-55 years of age who were referred to various health centers in Ardabil, Iran in 2013-2014. Samples were blocked randomly and divided into two intervention (lavender) and control (diluted milk) groups. Lavender aroma was smelled for 20 minutes twice a day, over a 12-week period. Data were collected using a demographic questionnaire, and flushing numbers were duly recorded. Data analysis was performed by SPSS version 16 (SPSS Inc., Chicago, IL, USA) using the Chi-square and t test. RESULTS: The results of our investigation showed that both groups had no significant difference according to demographic characteristics (p > 0.05). Additionally, the flushing number significantly decreased in the intervention group than in the control group (p < 0.001). CONCLUSION: This study indicated that the use of lavender aromatherapy reduced menopause flushing. Given the impact of stress on flushing and the undesirable effects of menopause symptoms on the quality of life, it would appear that this simple, noninvasive, safe, and effective method can be used by menopausal women with noticeable benefits. PMID- 27388436 TI - Next-Generation Sequencing of an 88-Year-Old Specimen of the Poorly Known Species Liagora japonica (Nemaliales, Rhodophyta) Supports the Recognition of Otohimella gen. nov. AB - Liagora japonica is a red algal species distributed in temperate regions of Japan. This species has not been collected from its type locality on the Pacific coast of Japan since 1927 and seems to have become extinct in this area. For molecular characterization of L. japonica, we extracted DNA from the topotype material of L. japonica collected in 1927, analyzed seven genes using Illumina next-generation sequencing, and compared these data with sequences from modern samples of similar red algae collected from the Japan Sea coast of Japan. Both morphological and molecular data from modern samples and historical specimens (including the lectotype and topotype) suggest that the specimens from the Pacific and Japan Sea coasts of Japan should be treated as a single species, and that L. japonica is phylogenetically separated from the genus Liagora. Based on the phylogenetic results and examination of reproductive structures, we propose Otohimella japonica gen. et comb. nov., characterized morphologically by diffuse carposporophytes, undivided carposporangia, and involucral filaments initiated only from the cortical cell on the supporting cell. PMID- 27388437 TI - Association between trauma and socioeconomic deprivation: a registry-based, Scotland-wide retrospective cohort study of 9,238 patients. AB - BACKGROUND: Trauma remains a leading cause of morbidity and mortality in the UK and throughout the world. Socioeconomic deprivation has been linked with many types of ill-health and previous studies have shown an association with injury in other parts of the world. The aim of this study was to investigate the association between socioeconomic deprivation and trauma incidence and case fatality in Scotland. METHODS: The study included nine thousand two hundred and thirty eight patients attending Emergency Departments following trauma across Scotland in 2011-12. A retrospective cohort study was conducted using secondary data extracted from the national trauma registry. Postcode of residence was used to generate deciles using the Scottish Index of Multiple Deprivation. The incidence rate ratio (IRR) was calculated to allow comparison of incidence of trauma across SIMD deciles. For mortality, observed: expected ratios were obtained using observed mortality in the cohort and expected deaths using probability of survival based on Trauma and Injury Severity Score (TRISS) method. RESULTS: Compared with the most deprived decile, the least deprived had an incidence rate ratio (IRR) for all trauma of 0.43 (95 % CI 0.32-0.58, p < 0.001). The association was stronger for penetrating trauma (IRR 0.07, 95 % CI .01-0.56, p = 0.011). There was a significant interaction between age, gender and SIMD. For case fatality, multivariate logistic regression showed that, severity of trauma (ISS > 15) OR 18.11 (95 % CI 13.91 to 23.58) and type of injury (Penetrating versus blunt injury) OR 2.07 (95 % CI 1.15 to 3.72) remain as independent predictors of case fatality in this dataset. DISCUSSION: Our data shows a higher incidence of trauma amongst a socioeconomically deprived population, in keeping with other areas of the world. In our dataset, outcome, as measured by in hospital mortality, does not appear to be associated with socioeconomic deprivation. CONCLUSION: In Scotland, populations living in socioeconomically deprived areas have a higher incidence of trauma, especially penetrating trauma, requiring hospital attendance. Case fatality is associated with more severe trauma and penetrating trauma, but not socioeconomic deprivation. PMID- 27388438 TI - Correction: A versatile two-photon fluorescent probe for ratiometric imaging E. colibeta-galactosidase in live cells and in vivo. AB - Correction for 'A versatile two-photon fluorescent probe for ratiometric imaging E. colibeta-galactosidase in live cells and in vivo' by Xue-Xiang Zhang et al., Chem. Commun., 2016, 52, 8283-8286. PMID- 27388439 TI - Comparing Maternal Services Utilization and Expense Reimbursement before and after the Adjustment of the New Rural Cooperative Medical Scheme Policy in Rural China. AB - BACKGROUND: The New Rural Cooperative Medical Scheme (NCMS) includes a maternal care benefits package that is associated with increasing maternal health services. The local compensation policies have been frequently adjusted in recent years. This study examined the association between the NCMS maternal-services policy adjustment and expense reimbursement in Yuyao, China. METHODS: Two household surveys were conducted in Yuyao in 2008 and 2011 (before and after the NCMS policy adjustment, respectively). Local women (N = 154) who had delivery history in the past three years were recruited. A questionnaire was used to collect information about delivery history, maternal health services utilization (prenatal care, postnatal care, and the grade of delivery institutions), NCMS participation, and reimbursement status. Logistic regression analyses were used to predict the association between policy adjustment and maternal health utilization and the association between policy adjustment and out-of-pocket proportion. Next, t-tests and covariance analyses adjusting for household income were used to compare the out-of-pocket proportion between 2008 and 2011. RESULTS: Results revealed that compensation policy adjustment was associated with an increase in postnatal visits (adjusted OR = 3.32, p = 0.009) and the use of second level or above institutions for delivery (adjusted OR = 2.32, p = 0.03) among participants. In 2008, only 9.1% of pregnant women received reimbursement from the NCMS; however, this rate increased to 36.8% in 2011. After policy adjustment, there were no significant changes in the proportion of out-of-pocket expenses shared in delivery fee (F = 0.24, p = 0.63) and in household income (F = 0.46, p = 0.50). CONCLUSIONS: Financial compensation increase improved maternal health services utilization; however, this effect was limited. Although the reimbursement rate was raised, the out-of-pocket proportion was not significant changed; therefore, the compensation design scheme must be adjusted in practice. PMID- 27388440 TI - Reducing major lower extremity amputations after the introduction of a multidisciplinary team in patient with diabetes foot ulcer. AB - BACKGROUND: Diabetic foot ulceration is receiving more attention because of its high amputation and mortality rate. It is essential to establish the frequency of amputations in people with diabetes after any change to the management of diabetic foot care. The present study aim to compare the frequency of lower extremity amputations in patients with diabetes foot ulcer over a ten-year period. METHODS: Six hundred forty eight patients with diabetes foot ulcer were retrospectively studied from 2004 to 2013. The clinical features, laboratory results and the lower-extremity amputations were recorded. Major amputation was defined as amputations above the ankle while minor amputation was amputations below the ankle in the present study. RESULTS: Patients with diabetic foot ulcer were old (age 66.96 +/- 11.96 years), with a long duration of diabetes (10.30 +/- 6.94 years), high HbA1c (9.19 +/- 2.62 %), SBP (144.05 +/- 24.18 mmHg), DBP (79.53 +/- 11.88 mmHg), LDL-C (2.71 +/- 0.93 mmol/L) and had great frequency of neuropathy (62.7 %), retinopathy (45.0 %), nephropathy (39.5 %) and PAD (33.2 %). From 2004 to 2013, the frequency of all lower-extremity amputations is 12.0 % (5.2 % major amputation, 6.8 % minor amputation). The frequency of major amputations decreased from 9.5 % in 2004 and 14.5 % in 2005 to less than 5.0 % after 2006. In particular, there was a significant decline in major amputations of diabetic foot patient with Wagner 3 to 4 wounds. The frequency rate of major amputations in diabetic foot patient with Wagner 3 to 4 wounds fell from 35.7 % in 2004 to 4.4 % after 2007. The change in frequency of minor amputations was fluctuation. CONCLUSION: This study demonstrates that the introduction of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist, for managing diabetic foot disease is associated with a reduction in the frequency of major amputations in patients with diabetes. PMID- 27388441 TI - Effects of a Randomised Controlled School-Based Health Promotion Intervention on Obesity Related Behavioural Outcomes of Children with Migration Background. AB - Children with migration background (MB) appear to be at higher risk of developing obesity, therefore, prevention is necessary to avoid possible health inequalities. This study investigated a 1-year intervention with focus on increasing physical activity (PA) and fruit and vegetable intake (FVI), decreasing screen media use (SMU) and soft drink consumption (SDC) in children with MB. 525 children (7.1 +/- 0.7 years) with MB who participated in the cluster randomised study were assessed at baseline and after 1 year. Daily SMU, PA behaviours, SDC and FVI were assessed using a parental questionnaire. After one year, significant effects were found in the intervention group for FVI (p <= 0.035). Partially strong tendencies but no significant differences were found for PA and SDC. Although the effects are small, the intervention seems to reach children with MB. An intervention lasting longer than one year might result in more changes. PMID- 27388442 TI - A Systematic Review of HIV Serostatus Disclosure Among African Immigrants in Europe. AB - As the human immunodeficiency virus continues to devastate large parts of Africa, particularly the Sub-Saharan region, the number of immigrants migrating from these areas to European nations continues to grow. African men and women leave their countries for Europe because of armed conflicts, unemployment, or poverty. Thus, these migration patterns combined with newly contracted infections have resulted in a large and growing number of HIV-positive diagnoses among African immigrants living in Europe. Using the disclosure process model, this systematic review examines the reasons for HIV status disclosure and nondisclosure among African immigrants residing in Europe. PubMed, PsycINFO, Embase, Global Health, and Web of Science were searched. Bibliographies of retrieved studies were also reviewed for other relevant citations. Studies were eligible if they: (1) focused on HIV-positive immigrants from SSA residing in Europe; and (2) described or measured HIV status disclosure. Out of 166 articles found, a total of 17 articles and 1 brief report met the inclusion criteria. Factors such as stigma and social implications of disclosure contribute to avoidance goals leading to nondisclosure while approach goals or disclosure reasons were found to include health status and behaviors such as seeking support, and helping others. The findings highlight the importance of understanding the avoidance and approach goals involved in HIV status disclosure among African immigrants in Europe. Interventions and future research directed at increasing HIV disclosure among African immigrants in Europe should move beyond individual-level to consider multilevel factors including country-specific social behaviors. PMID- 27388443 TI - Methotrexate Nanoparticles Prepared with Codendrimer from Polyamidoamine (PAMAM) and Oligoethylene Glycols (OEG) Dendrons: Antitumor Efficacy in Vitro and in Vivo. AB - The novel methotrexate-loaded nanoparticles (MTX/PGD NPs) prepared with amphiphilic codendrimer PGD from polyamidoamine and oligothylene glycol dendrons were obtained via antisolvent precipitation method augmented by ultrasonication. Based on the excellent hydrophility of PGD, the drug-loaded nanoparticles could be investigated easily with the high drug-loading content (~85.2%, w/w). The MTX/PGD NPs possessed spherical morphology, nanoscaled particle size (approximately 182.4 nm), and narrow particle size distribution. Release of MTX from MTX/PGD NPs showed a sustained release manner and completed within 48 h. Hemolytic evaluation indicated MTX/PGD NPs presented good blood compatibility, and the cytotoxicity of nanoparticles against breast cancer cells in vitro, biodistribution in tumor tissue, and antitumor efficacy in vivo were enhanced significantly compared to MTX injection. According to the higher drug-loading content, enhanced antitumor efficacy, and appropriate particle size, MTX/PGD NPs as the drug delivery systems could have potential application for cancer chemotherapy in clinic. PMID- 27388444 TI - Predictive Factors for Efficacy and Safety of Prophylactic Theophylline for Extubation in Infants with Apnea of Prematurity. AB - PURPOSE: This study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP) after weaning from mechanical ventilation. METHODS: We retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine) for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013. RESULTS: A total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0%) infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p < 0.001). Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline (specificity, 66.7%; sensitivity, 86.6%; p < 0.001; area under the curve, 0.750; 95% confidence interval, 0.45-0.74). Adverse reactions were identified in 21 (21.0%) infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01). CONCLUSIONS: Physicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth. PMID- 27388446 TI - Impact of factitious foods and prey on the oviposition of the predatory mites Gaeolaelaps aculeifer and Stratiolaelaps scimitus (Acari: Laelapidae). AB - The soil-dwelling predatory mites Gaeolaelaps aculeifer and Stratiolaelaps scimitus (Mesostigmata: Laelapidae) are important biocontrol agents of several pests (Astigmata, Thysanoptera, Diptera). There is little information regarding the use of factitious foods that potentially improve their mass rearing and population development once released in the field. Here we tested the suitability of several types of factitious food and prey for G. aculeifer and S. scimitus. Factitious foods included eggs of Ephestia kuehniella (Lepidoptera: Pyralidae), hydrated encapsulated cysts of the brine shrimp Artemia sp. (Anostraca: Artemiidae), two species of saprophytic nematodes (Panagrellus redivivus and Panagrellus sp.) (Nematoda: Panagrolaimidae) and pollen of cattail Typha angustifolia (Poales: Typhaceae). Parameters tested were oviposition over a 3-day period compared with controls provided with either second instars of the thrips Frankliniella occidentalis (Thysanoptera: Thripidae) or a mix of instars of the commercially used prey mite Tyrophagus putrescentiae (Astigmatina: Acaridae) or the absence of food. Compared to the standard prey mite T. putrescentiae, G. aculeifer showed elevated oviposition when fed thrips larvae, E. kuehniella eggs, Artemia sp. cysts or the saprophytic P. redivivus. Oviposition by S. scimitus was high when provided with thrips larvae and P. redivivus, but not significantly different from oviposition on T. putrescentiae. Oviposition for both predatory mite species was very low or zero when provided with T. angustifolia pollen. Finally, G. aculeifer consumed significantly more thrips larvae than S. scimitus. The implication of these results for the mass-rearing of G. aculeifer and S. scimitus are discussed. PMID- 27388445 TI - Health-related quality of life in older depressed psychogeriatric patients: one year follow-up. AB - BACKGROUND: Knowledge about long-term change in health related quality of life (HQoL) among older adults after hospitalization for treatment of depression has clinical relevance. The aim was firstly to describe the change of HQoL one year after admission for treatment of depression, secondly to explore if improved HQoL was associated with remission of depression at follow-up and lastly to study how HQoL in patients with remission from depression were compared to a reference group of older persons without depression. METHOD: This study had the one year follow-up information of 108 older patients (>=60 years), all hospitalized for depression at baseline, and a reference sample of 106 community-living older adults (>=60 years) without depression. HQoL was measured using the EuroQol Group's EQ-5D Index and a visual analog scale (EQ-VAS). Depression and remission were diagnosed according to ICD-10. Socio-demographic variables (age, gender, and education), depressive symptom score (Montgomery-Aasberg Depression Rating Scale), cognitive functioning (Mini Mental State Examination scale), instrumental activities of daily living (the Lawton and Brody's Instrumental Activities of Daily Living Scale), and poor general physical health (General Medical Health Rating) were included as covariates. RESULTS: HQoL had improved at follow-up for the total group of depressed patients, as indicated by better scores on the EQ-5D Index and EQ-VAS. In the multivariate linear regression model, improved EQ-5D Index and EQ-VAS was significantly better in those with remission of depression and those with better baseline physical health. In adjusted analyses, the HQoL in patients with remission from depression at follow-up did not differ from the HQoL in a reference group without depression. CONCLUSION: Older hospital patients with depression who experienced remission one year after admission gained HQoL and their HQoL was comparable with the HQoL in a reference group of older adults without depression when adjusting for differences in socio-demographics and health conditions. PMID- 27388447 TI - Functional analysis of a chitinase gene during the larval-nymph transition in Panonychus citri by RNA interference. AB - Chitinases are hydrolytic enzymes that are required for chitin degradation and reconstruction in arthropods. In this study, we report a cDNA sequence encoding a putative chitinase (PcCht1) from the citrus red mite, Panonychus citri. The PcCht1 (564 aa) possessed a signal peptide, a conserver domain, and a chitin binding domain. Structural and phylogenetic analyses found that PcCht1 had high sequence similarity to chitinases in Tetranychus urticae. Real-time quantitative PCR analyses showed that the transcript levels of PcCht1 peaked periodically in larval and nymph stages. Moreover, significant increase of PcCht1 transcript level in the larvae was observed upon the exposure of diflubenzuron. In contrast, exposures of the larvae to diflubenzuron resulted in the decreased chitin content. Furthermore, through a feeding-based RNA interference approach, we were able to reduce the PcCht1 transcript level by 59.7 % in the larvae, and consequently the treated larvae showed a very low molting rate compared with the control. Our results expanded the understanding of the important role of PcCht1 in the growth and development of P. citri. PMID- 27388448 TI - Change in abundance of three phytophagous mite species (Acari: Eriophyidae, Tetranychidae) on quackgrass in the presence of choke disease. AB - Phytophagous mites and endophytic fungi may interact when sharing a host plant, potentially influencing one another's growth or population dynamics; however, interactions between them are poorly known and remain largely unexplored. In this study, quantitative associations between three species of phytophagous mites and the endophytic fungus Epichloe bromicola Leuchtm. & Schardl (Clavicipitaceae, Ascomycotina) on quackgrass, Elymus repens (L.) Gould are reported. The mites' abundance was assessed on field-collected grass shoots that were either exhibiting choke disease symptoms or without the fungus. Overall, the abundance of Tetranychus urticae and Aculodes mckenziei was significantly lower on quackgrass plants infected by E. bromicola compared to plants without the fungus. Conversely, populations of Abacarus hystrix were significantly larger on plants colonised by the fungus than on uninfected plants. Thus, the presence of this endophytic fungus may have divergent effects on different phytophagous mite species although the basis of these effects is not yet known. PMID- 27388449 TI - European policies on tuberculosis prevention in healthcare workers: Which role for BCG? A systematic review. AB - National recommendations regarding the immunization of healthcare workers (HCWs) against tuberculosis differ throughout Europe. We searched multiple sources to identify legal acts, guidelines or papers addressing European national policies on BCG immunization for HCWs. For each policy, we reviewed the criteria used to recommend immunization, their level of evidence, the evidence supporting them and the actions required in cases of refusal. Four legal acts, 15 policies and 6 papers from 14 European countries met the inclusion criteria. Among European national agencies, 5 only recommend the immunization of HCWs employed in high risk sectors, highlighting the lack of evidence of Bacillus Calmette-Guerin (BCG) efficacy in HCWs; 5 recommend BCG vaccination for all previously unvaccinated Mantoux-negative HCWs, underlining that some studies provide arguments of some BCG efficacy in HCWs; and four do not recommend the vaccine. Different interpretations of existing evidence on BCG efficacy and the demographics of HCWs may have influenced national policies. PMID- 27388450 TI - Transient renal impairment in the absence of pre-existing chronic kidney disease in patients with unilateral ureteric stone impaction. AB - This study aims to describe the rate and characteristics of transient renal impairment in unilateral ureteric stone patients without chronic kidney disease (CKD) and to identify factors that may have influenced renal function of these patients. Unilateral ureteric stone patients who visited our hospital's emergency department from December, 2009 to December, 2015 were divided into two groups based on estimated glomerular filtration rate (eGFR): group I (patients with eGFR >= 60 ml/min/1.73 m2) and group II (eGFR < 60 ml/min/1.73 m2). A univariate comparison between groups I and II was performed. Multivariable logistic regression analysis was performed to determine factors that influenced renal function. There were 107 patients in group II, which constituted 5.6 % of the total patients. In the multivariable logistic regression analysis, age (p < 0.001, odds ratio [OR] = 1.069, confidence interval [CI] = 1.049-1.089), hypertension (p < 0.001, OR = 2.302, CI = 1.467-3.611), stone size (p = 0.001, OR = 1.141, CI = 1.057-1.231), white blood cell count (p = 0.001, OR = 1.132, CI = 1.055-1.215) and hematuria (p < 0.001, OR = 0.383, CI = 0.231-0.636) were found to be independent factors for renal impairment. Based on the results of this study, the rate of renal impairment was 6 % of the unilateral ureteric stone patients without pre-existing CKD. Age and hypertension were found to be independent factors for renal impairment; NSAIDs should be used cautiously or other agents for pain relief such as opioids should be considered in old aged patients with hypertension. PMID- 27388452 TI - Early Intervention in Lung Cancers With Rapid Plasma Genotyping for EGFR and KRAS Mutations-Reply. PMID- 27388451 TI - Vector competence of northern European Culex pipiens biotypes and hybrids for West Nile virus is differentially affected by temperature. AB - BACKGROUND: Outbreaks of West Nile virus (WNV) have not occurred in northern Europe despite nearby circulation of WNV in the southern part of the continent. The main vector for WNV, the mosquito Culex (Cx.) pipiens, consists of two behaviorally distinct biotypes, pipiens and molestus, which can form hybrids. Although temperature has been shown to influence vector competence of Cx. pipiens for WNV and biotypes are differentially susceptible towards infection, the interaction between the two has not been elucidated. METHODS: We determined vector competence of the Cx. pipiens biotypes and hybrids, after 14 days of incubation at 18, 23 and 28 degrees C. Mosquitoes were orally infected by providing an infectious blood meal or by injecting WNV directly in the thorax. Infection and transmission rates were determined by testing the bodies and saliva for WNV presence. In addition, titers of mosquitoes with WNV-positive bodies and saliva samples were determined. RESULTS: Orally infected biotype pipiens and hybrids showed significantly increased transmission rates with higher temperatures, up to 32 and 14 %, respectively. In contrast, the molestus biotype had an overall transmission rate of 10 %, which did not increase with temperature. All mosquitoes that were infected via WNV injections had (close to) 100 % infection and transmission rates, suggesting an important role of the mosquito midgut barrier. We found no effect of increasing temperature on viral titers. CONCLUSIONS: Temperature differentially affected vector competence of the Cx. pipiens biotypes. This shows the importance of accounting for biotype-by temperature interactions, which influence the outcomes of vector competence studies. Vector competence studies with Cx. pipiens mosquitoes differentiated to the biotype level are essential for proper WNV risk assessments. PMID- 27388453 TI - Thoracic magnetic resonance venography using Gadofosveset in patients with venous pathology-A comparative study of image quality and inter-rater variability. AB - Background High-quality non-invasive imaging of the deep venous system in the thorax is challenging, but nevertheless required for diagnosis of vascular pathology as well as for patient selection and preoperative planning for endovascular procedures. Purpose To compare the diagnostic quality of Gadofosveset-enhanced thoracic magnetic resonance venography, seven consecutive patients with suspected or known disease affecting the central thoracic veins were compared to seven consecutive magnetic resonance venography using conventional gadolinium-based contrast agents. Materials and methods Diagnostic capability, defined as the ability to assess vessel patency and pathologic conditions, for the major thoracic deep venous segments was assessed by two independent readers. Both reviewers rated the overall subjective image quality on a four-graded scale, and inter-rater variability was analyzed using unweighted and weighted Cohen's kappa values. Results Diagnostic capability was generally considerably higher in the Gadofosveset group for all examined vessel segments. The overall images quality rating was significantly higher for the Gadofosveset group with a mean rating of 2.9 and 2.7 for the two-independent readers, compared to 1.2 and 1.0 for the control croup. Inter-rater variability showed less variability for the Gadofosveset group with a quadratic-weighted Cohen's Kappa value of 0.58 compared to 0.36 for the control group. Conclusion Our results show that Gadofosveset-enhanced magnetic resonance venography of the central thoracic veins is a reliable technique in clinical routine practice that results in diagnostic images, superior to conventional gadolinium-based contrast medium. PMID- 27388454 TI - Regioselective, Solvent- and Metal-Free Chalcogenation of Imidazo[1,2-a]pyridines by Employing I2 /DMSO as the Catalytic Oxidation System. AB - Highly efficient molecular-iodine-catalyzed chalcogenations (S and Se) of imidazo[1,2-a]pyridines were achieved by using diorganoyl dichalcogenides under solvent-free conditions. This approach afforded the desired products that had been chalcogenated regioselectively at the C3 position in up to 96 % yield by using DMSO as an oxidant, in the absence of a metal catalyst, and under an inert atmosphere. This mild, green approach allowed the preparation of different types of chalcogenated imidazo[1,2-a]pyridines with structural diversity. Furthermore, the current protocol was also extended to other N-heterocyclic cores. PMID- 27388455 TI - The role of membrane ERalpha signaling in bone and other major estrogen responsive tissues. AB - Estrogen receptor alpha (ERalpha) signaling leads to cellular responses in several tissues and in addition to nuclear ERalpha-mediated effects, membrane ERalpha (mERalpha) signaling may be of importance. To elucidate the significance, in vivo, of mERalpha signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ERalpha to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mERalpha signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mERalpha (<35% reduction in estrogen response in NOER mice). In conclusion, mERalpha signaling is important for the estrogenic response in female mice in a tissue dependent manner. Increased knowledge regarding membrane initiated ERalpha actions may provide means to develop new selective estrogen receptor modulators with improved profiles. PMID- 27388456 TI - Erratum to: Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil. PMID- 27388457 TI - Psychosocial factors influencing risk-taking in middle age for STIs. AB - OBJECTIVES: To increase the knowledge of the psychosocial factors influencing sexual risk-taking for STIs among adults in late middle age. METHODS: Individual interviews were conducted either face to face or by telephone with 31 heterosexual men and women aged between 45 and 65. They were recruited from NHS sexual health services (n=16) and council run culture and leisure facilities (n=15) in a large Scottish city. A total of 18 women and 13 men were interviewed. All interviews were transcribed in full and thematically analysed. RESULTS: Analysis detailed important psychosocial and sociocultural factors; the prioritisation of intimacy above and beyond concerns about risks for STI in sexual partnerships; the importance of unwanted pregnancy in shaping risk perceptions throughout the life course; vulnerability associated with periods of relationship transition (eg, bereavement, divorce or separation); social norms and cultural expectations relating to age-appropriate sexual and health-seeking behaviours. CONCLUSIONS: This is the first qualitative study to examine the factors associated with sexual risk-taking among heterosexual adults in late middle age in the UK. Many factors associated with sexual risk-taking are similar to those reported within other populations. However, we also detail population specific factors, which should be considered in terms of the development of interventions for 'at risk' older adults, or the tailoring of wider behaviour change interventions to this specific age group. PMID- 27388458 TI - Factors associated with consistent condom use and STIs among foreign female entertainment workers: results from a cross-sectional survey in Singapore. AB - OBJECTIVES: We assessed the prevalence of consistent condom use and laboratory confirmed STIs among foreign female entertainment workers (FEWs) who engaged in paid or casual sex in Singapore and the factors associated with these characteristics. METHODS: A cross-sectional survey, using time-location sampling, was conducted on 220 FEWs (115 Vietnamese and 105 Thai) in 2015. For multivariable analysis, we used a mixed-effects Poisson regression model with backward stepwise approach to account for clustering by venue and to obtain the adjusted prevalence ratios (aPRs) of factors associated with consistent condom use and STI positivity, respectively. RESULTS: Consistent condom use with paid or casual partners in the past month was 39.6% and 36.2% for vaginal and oral sex, respectively. The prevalence of STI (cervical chlamydia, cervical gonorrhoea or pharyngeal gonorrhoea) positivity was 13.6%. In multivariable analysis, consistent condom use for both vaginal and oral sex increased with high self perceived risk of getting STI/HIV (vaginal: aPR 2.09; 95% CI 1.26 to 3.46; oral: aPR 2.41; 95% CI 1.23 to 4.69) and condom negotiation (vaginal: aPR 3.74; 95% CI 2.07 to 6.75; oral: aPR 2.81; 95% CI 1.51 to 5.26). STI positivity decreased with consistent condom use for vaginal sex (aPR 0.22; 95% CI 0.07 to 0.75) and increased with number of sexual partners (aPR 1.43; 95% CI 1.07 to 1.92). CONCLUSION: In addition to advocating for policy decisions to provide a safer work environment, behavioural interventions on condom negotiation skills and condom use and biomedical interventions on STI/HIV testing and treatment interventions are needed among the FEWs in Singapore. TRIAL REGISTRATION NUMBER: NCT02780986; pre-results. PMID- 27388459 TI - Households, the omitted level in contextual analysis: disentangling the relative influence of households and districts on the variation of BMI about two decades in Indonesia. AB - BACKGROUND: Most of the research investigating the effect of social context on individual health outcomes has interpreted context in terms of the residential environment. In these studies, individuals are nested within their neighbourhoods or communities, disregarding the intermediate household level that lies between individuals and their residential environment. Households are an important determinant of health yet they are rarely included at the contextual level in research examining association between body mass index (BMI) and the social determinants of health. In this study, our main aim was to provide a methodological demonstration of multilevel analysis, which disentangles the simultaneous effects of households and districts as well as their associated predictors on BMI over time. METHODS: Using both two- and three-level multilevel analysis, we utilized data from all four cross-sections of the Indonesian Family life Survey (IFLS) 1993 to 2007-8. RESULTS: We found that: (i) the variation in BMI attributable to districts decreased from 4.3 % in 1993 to 1.5 % in 1997-98, and remained constant until 2007-08, while there was an alarming increase in the variation of BMI attributable to households, from 10 % in 2000 to 15 % in 2007 08; (ii) ignoring the household level did not change the relative variance contribution of districts on BMI, but ignoring the district level resulted in overestimation of household effects, and (iii) households' characteristics (socioeconomic status, size, and place of residence) did not attenuate the variation of BMI at the household-level. CONCLUSIONS: Estimating the relative importance of multiple social settings allows us to better understand and unpack the variation in clustered or hieratical data in order to make valid and robust inferences. Our findings will help direct investment of limited public health resources to the appropriate context in order to reduce health risk (variation in BMI) and promote population health. PMID- 27388460 TI - Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals. AB - BACKGROUND: Our view of host-associated microbiota remains incomplete due to the presence of as yet uncultured constituents. The Bacteroidales family S24-7 is a prominent example of one of these groups. Marker gene surveys indicate that members of this family are highly localized to the gastrointestinal tracts of homeothermic animals and are increasingly being recognized as a numerically predominant member of the gut microbiota; however, little is known about the nature of their interactions with the host. RESULTS: Here, we provide the first whole genome exploration of this family, for which we propose the name "Candidatus Homeothermaceae," using 30 population genomes extracted from fecal samples of four different animal hosts: human, mouse, koala, and guinea pig. We infer the core metabolism of "Ca. Homeothermaceae" to be that of fermentative or nanaerobic bacteria, resembling that of related Bacteroidales families. In addition, we describe three trophic guilds within the family, plant glycan (hemicellulose and pectin), host glycan, and alpha-glucan, each broadly defined by increased abundance of enzymes involved in the degradation of particular carbohydrates. CONCLUSIONS: "Ca. Homeothermaceae" representatives constitute a substantial component of the murine gut microbiota, as well as being present within the human gut, and this study provides important first insights into the nature of their residency. The presence of trophic guilds within the family indicates the potential for niche partitioning and specific roles for each guild in gut health and dysbiosis. PMID- 27388461 TI - Delphinidin-3-glucoside suppresses breast carcinogenesis by inactivating the Akt/HOTAIR signaling pathway. AB - BACKGROUND: The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) plays a crucial role in cancer progression, which is regulated by the interferon regulatory factor-1 (IRF1) and up-streaming Akt activation. The present study evaluated the chemopreventive effects of delphinidin-3-glucoside (Dp), a major anthocyanin present in pigmented fruits and vegetables, on breast carcinogenesis, and investigate the role of the Akt/HOTAIR signaling pathway. METHODS: Human breast epithelial cells MCF10A were treated with carcinogens (NNK and B[a]P) or co-treated with carcinogens plus Dp for 30 days. Then, the cancer associated properties of the treated cells were evaluated to assess the carcinogenesis and the effects of Dp. HOTAIR levels were detected by qRT-PCR. The proteins expression was measured by western blots, immunofluorescence and immunohistochemistry. Xenografted tumors were made by implanting breast cancer cells MDA-MB-231-Luc-GFP in athymic mice. ChIP-qPCR analysis was used to detect the IRF1 binding to the HOTAIR promoter. RESULTS: Carcinogens treatment induces apparent carcinogenic transformation in MCF10A cells including reduced dependence on growth factors, anchorage-independent cell growth and aberrant wound-healing ability, which is effectively suppressed by Dp co-treatment. The level of HOTAIR significantly increases in a time-dependent manner during chronic breast carcinogenesis. Dp treatment down-regulates HOTAIR expression in breast carcinogenesis and breast cancer cells. Furthermore, Dp administration inhibits the growth of xenografted breast tumors in athymic mice, and decreases HOTAIR in vivo. Further studies showed that Dp represses Akt activation, promotes IRF1 expression and increases IRF1 binding to the HOTAIR promoter. Silence of IRF1 expression via transfecting cells with IRF1 siRNAs significantly reduced the effects of Dp on HOTAIR, resulting in decreased cytotoxic effects of Dp on breast cancer cells. CONCLUSIONS: These data suggest the effective chemopreventive effect of Dp on breast carcinogenesis, in which down-regulation of HOTAIR plays a critical role. PMID- 27388462 TI - Coffee, tea and caffeine intake and the risk of non-melanoma skin cancer: a review of the literature and meta-analysis. AB - PURPOSE: Laboratory studies suggested that caffeine and other nutrients contained in coffee and tea may protect against non-melanoma skin cancer (NMSC). However, epidemiological studies conducted so far have produced conflicting results. METHODS: We performed a literature review and meta-analysis of observational studies published until February 2016 that investigated the association between coffee and tea intake and NMSC risk. We calculated summary relative risk (SRR) and corresponding 95 % confidence intervals (95 % CI) by using random effects with maximum likelihood estimation. RESULTS: Overall, 37,627 NMSC cases from 13 papers were available for analysis. Intake of caffeinated coffee was inversely associated with NMSC risk (SRR for those in the highest vs. lowest category of intake: 0.82, 95 % CI 0.75-0.89, I 2 = 48 %), as well as intake of caffeine (SRR 0.86, 95 % CI 0.80-0.91, I 2 = 48 %). In subgroup analysis, these associations were limited to the basal cell cancer (BCC) histotype. There was no association between intake of decaffeinated coffee (SRR 1.01, 95 % CI 0.85-1.21, I 2 = 0) and tea (0.88, 95 % CI 0.72-1.07, I 2 = 0 %) and NMSC risk. There was no evidence of publication bias affecting the results. The available evidence was not sufficient to draw conclusions on the association between green tea intake and NMSC risk. CONCLUSIONS: Coffee intake appears to exert a moderate protective effect against BCC development, probably through the biological effect of caffeine. However, the observational nature of studies included, subject to bias and confounding, suggests taking with caution these results that should be verified in randomized clinical trials. PMID- 27388463 TI - Effects of Lentinula edodes consumption on biochemical, hematologic and oxidative stress parameters in rats receiving high-fat diet. AB - PURPOSE: Functional foods can prevent/reduce the risks related to obesity. Lentinula edodes is a highly nutritious mushroom rich in protein, vitamins and minerals. Some studies have demonstrated the hypocholesterolemic effects from L. edodes in high doses, which does not represent the consumption in humans. We evaluated ingestion of a realistic dose of L. edodes associated with a high-fat diet (HFD) on hematologic, biochemical and oxidative stress parameters. METHODS: Eighteen male Wistar rats were divided into three groups: control (normal diet); HFD; and HFD + L. edodes (100 mg/kg/day). After 30 days, blood was collected. Biochemical and hematologic parameters were analyzed, as well as oxidative stress biomarkers. RESULTS: The HFD increased levels of total cholesterol and triglycerides. Lentinula edodes reduced these parameters significantly to concentrations found in the control group. The HFD increased levels of alanine transaminase and aspartate transaminase (markers of liver damage). Lentinula edodes returned the levels of these enzymes to normal levels and normalized serum levels of urea (which were also increased owing to consumption of the HFD). Lentinula edodes reduced levels of urea and glucose. Lipid peroxidation was increased in rats receiving the HFD, and L. edodes reduced malondialdehyde levels, thereby preventing oxidation of fatty acids. CONCLUSIONS: Lentinula edodes was shown to have hypolipidemic, hypoglycemic, hepatoprotective and renoprotective features in doses that are suitable for humans. PMID- 27388465 TI - Blurring the line between life and death: a review of the psychological and ethical concerns related to posthumous-assisted reproduction. AB - Posthumous-assisted reproduction (PAR), though viewed unfavourably by some, is desirable to many individuals whose partners die prior to the completion of family building. PAR is technically feasible for males and females both pre- and post-mortem and these procedures have previously been completed on numerous occasions. However, such treatment is associated with three primary ethical concerns: autonomy; beneficence; and justice for the living, the deceased, and the soon-to-be conceived. Further, there are many psychological risks of PAR which may affect all involved parties. As such, early psychological counselling of patients and surviving family members is warranted. PMID- 27388464 TI - Fruitflow(r): the first European Food Safety Authority-approved natural cardio protective functional ingredient. AB - Hyperactive platelets, in addition to their roles in thrombosis, are also important mediators of atherogenesis. Antiplatelet drugs are not suitable for use where risk of a cardiovascular event is relatively low. It is therefore important to find alternative safe antiplatelet inhibitors for the vulnerable population who has hyperactive platelets in order to reduce the risk of cardiovascular disease. Potent antiplatelet factors were identified in water-soluble tomato extract (Fruitflow(r)), which significantly inhibited platelet aggregation. Human volunteer studies demonstrated the potency and bioavailability of active compounds in Fruitflow(r). Fruitflow(r) became the first product in Europe to obtain an approved, proprietary health claim under Article 13(5) of the European Health Claims Regulation 1924/2006 on nutrition and health claims made on foods. Fruitflow(r) is now commercially available in different countries worldwide. In addition to its reduction in platelet reactivity, Fruitflow(r) contains anti angiotensin-converting enzyme and anti-inflammatory factors, making it an effective and natural cardio-protective functional food. PMID- 27388466 TI - Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study. AB - Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored >=4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy. PMID- 27388467 TI - Cortical functional activity in patients with generalized anxiety disorder. AB - BACKGROUND: The neurological correlates of Generalised Anxiety Disorder (GAD) are not well known, however there is evidence of cortical dysregulation in patients with GAD. The aim of the study was to examine cortical functional activity in different cerebral regions in patients with GAD using electroencephalogram (EEG) nonlinear analysis to evaluate its contribution of anxiety severity. METHODS: The cohorts consisted of 64 patients diagnosed with GAD as classified by the Structured Clinical Interview for the Diagnostic and Statistical Manual of the American Psychiatric Association-IV-TR. Anxiety severity was assessed using the Hamilton Rating Scale for Anxiety (HAMA) severity score, with 7 <= scores <= 17 indicating mild anxiety as A group (n = 31) and 18 and above indicating moderate severe anxiety as B group (n = 33). Participants with clinical levels of depression symptoms were excluded. A healthy control group comprising 30 participants was matched for age and gender. Closed eyes EEGs were conducted, and between-group differences on non-linear parameter Correlation Dimension (D2) were analyzed. The association of D2 value with HAMA scores was analyzed using multiple linear stepwise regression. RESULTS: Compared with the control group, D2 values were increased in anxiety groups (P < .05). For those with mild anxiety, this difference occurred in the left prefrontal regions (P < .05). For those with moderate-severe anxiety, significantly greater D2 values were observed in all of the cerebral regions, especially in the left cerebral regions and right temporal lobe (P < .01). When compared with those with mild anxiety, D2 values were significantly greater for those with moderate-severe anxiety in the right temporal lobe and all left cerebral regions except for left occipital lobe (P < .05). A positive correlation was observed between D2 values and moderate-severe anxiety HAMA scores. CONCLUSIONS: The increased D2 values were found in the majority of cerebral regions in GAD patients, especially in the left cerebral regions and the right temporal lobe. The increased GAD severity positively correlates to the D2 values in a larger number of cerebral regions. This analysis method can potentially be used as a complementary tool to examine dysfunctional cortical activity in GAD. PMID- 27388468 TI - [What do we know about perinatal sexuality? A scoping review on sexoperinatality part 1]. AB - The intimate and sexual dimension of future and new parenting couples' relationship is the most affected and the most vulnerable during the transition to parenthood; couples must adapt to support their relationship and their families. The purpose of this scoping review is to identify the literature that has been published on perinatal sexuality in the last 15 years. A total of 123 empirical articles were selected. This first article of a series of two is about sexuality during pregnancy. In addition to painting a picture from the chosen articles, 23 prenatal sexual variables were analyzed. The combined data present a diversified portrait of perinatal sexuality during pregnancy: the intimate and sexual experience varies during this period. Despite some exceptions, a certain tendency towards a gradual and progressive decline in most sexual behaviors and overall sexual expression during pregnancy was noted, with a marked decrease in early pregnancy and during the third trimester. Women are particularly affected by a greater number of sexual changes, but men are too. Many simultaneous physiological and psychological factors affect the sexual expression of the couples. Sexual fluctuations are a natural phenomenon during the transition to parenthood; couples must adjust to the new conditions and to the changes associated with sexuality during pregnancy, which are considered temporary. Sexoperinatal interventions should be a part of holistic perinatal health care in order to help couples maintain an intimate relationship and a healthy and positive sexual life. PMID- 27388469 TI - Incidence and possible causes of nontraumatic convexal subarachnoid haemorrhage in Chinese patients: A retrospective review. AB - Objective To explore the incidence and possible underlying pathogenic mechanisms of nontraumatic convexal subarachnoid haemorrhage (cSAH; a rarely reported condition) in a cohort of Chinese patients. Methods Medical records from all patients with subarachnoid haemorrhage (SAH) who had been treated at Peking University Third Hospital, China, between January 2010 and December 2014 were retrospectively reviewed to identify cases of cSAH. Results Of 144 patients with SAH, cSAH was observed in 14 cases (9.7%). The most frequent presenting symptoms in cSAH cases were severe headache ( n = 8) and a focal neurological deficit ( n = 8). The parietal (10/14 patients, 71.4%) and frontal (9/14 patients, 64.3%) lobes were the most common haemorrhage sites. Cause of cSAH was identified in 11 patients: in seven cases (50.0%), significant stenosis or occlusion in the internal carotid artery system, ipsilateral to cSAH, was reported; in four cases, cSAH was caused by cerebral venous sinus thrombosis, cerebrovascular malformation, anticoagulant therapy or possible cerebral amyloid angiopathy. Conclusion cSAH is an important subtype of nonaneurysmal SAH, with diverse aetiologies. In the present study, internal carotid artery system atherosclerotic stenosis was the most frequent cause of cSAH. PMID- 27388470 TI - Cell-free DNA increase over first 48 hours in emergency intensive care unit predicts fatal outcome in patients with shock. AB - Objective To investigate whether circulating cell-free (cf)-DNA levels are a useful biomarker for survival in patients with shock in the emergency intensive care unit (EICU). Methods This prospective observational study enrolled patients admitted to the EICU diagnosed with shock. Blood cf-DNA levels were analysed on admission, and after 24 and 48 h. As a measure of circulating cf-DNA, copy number of the beta-globin gene in plasma was assessed using quantitative real-time polymerase chain reaction. Results Circulating cf-DNA levels were higher at hospital admission and after 24 h in EICU patients with shock who died than in those who recovered. Change in cf-DNA levels over the first 48 h in critical care was independently associated with 28-day mortality. The critical cut-off value for cf-DNA change over 48 h in predicting 28-day mortality was +16.12% (sensitivity 68.9%, specificity 89.7%). Conclusions Increased circulating cf-DNA levels in EICU patients with shock are associated with risk of death and measuring cf-DNA change over 48 h improves risk prediction. The present study suggests that cf-DNA may serve as a viable plasma biomarker of mortality risk in EICU patients with shock. PMID- 27388471 TI - Curation of the genome annotation of Pichia pastoris (Komagataella phaffii) CBS7435 from gene level to protein function. AB - As manually curated and non-automated BLAST analysis of the published Pichia pastoris genome sequences revealed many differences between the gene annotations of the strains GS115 and CBS7435, RNA-Seq analysis, supported by proteomics, was performed to improve the genome annotation. Detailed analysis of sequence alignment and protein domain predictions were made to extend the functional genome annotation to all P. pastoris sequences. This allowed the identification of 492 new ORFs, 4916 hypothetical UTRs and the correction of 341 incorrect ORF predictions, which were mainly due to the presence of upstream ATG or erroneous intron predictions. Moreover, 175 previously erroneously annotated ORFs need to be removed from the annotation. In total, we have annotated 5325 ORFs. Regarding the functionality of those genes, we improved all gene and protein descriptions. Thereby, the percentage of ORFs with functional annotation was increased from 48% to 73%. Furthermore, we defined functional groups, covering 25 biological cellular processes of interest, by grouping all genes that are part of the defined process. All data are presented in the newly launched genome browser and database available at www.pichiagenome.org In summary, we present a wide spectrum of curation of the P. pastoris genome annotation from gene level to protein function. PMID- 27388472 TI - High hydrostatic pressure leads to free radicals accumulation in yeast cells triggering oxidative stress. AB - Saccharomyces cerevisiae is a unicellular organism that during the fermentative process is exposed to a variable environment; hence, resistance to multiple stress conditions is a desirable trait. The stress caused by high hydrostatic pressure (HHP) in S. cerevisiae resembles the injuries generated by other industrial stresses. In this study, it was confirmed that gene expression pattern in response to HHP displays an oxidative stress response profile which is expanded upon hydrostatic pressure release. Actually, reactive oxygen species (ROS) concentration level increased in yeast cells exposed to HHP treatment and an incubation period at room pressure led to a decrease in intracellular ROS concentration. On the other hand, ethylic, thermic and osmotic stresses did not result in any ROS accumulation in yeast cells. Microarray analysis revealed an upregulation of genes related to methionine metabolism, appearing to be a specific cellular response to HHP, and not related to other stresses, such as heat and osmotic stresses. Next, we investigated whether enhanced oxidative stress tolerance leads to enhanced tolerance to HHP stress. Overexpression of STF2 is known to enhance tolerance to oxidative stress and we show that it also leads to enhanced tolerance to HHP stress. PMID- 27388473 TI - ADCs Show Promise in Leukemias. AB - According to a phase III study, the antibody-drug conjugate inotuzumab ozogamicin is more likely to induce complete remissions, with full or incomplete hematologic recovery, in patients with relapsed or refractory acute lymphocytic leukemia. Data from a phase I study of another antibody-drug conjugate, vadastuximab talirine, demonstrates that it is safe and effective against acute myeloid leukemia. PMID- 27388474 TI - Optimized Mealtime Insulin Dosing for Fat and Protein in Type 1 Diabetes: Application of a Model-Based Approach to Derive Insulin Doses for Open-Loop Diabetes Management. AB - OBJECTIVE: To determine insulin dose adjustments required for coverage of high fat, high-protein (HFHP) meals in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Ten adults with T1D received low-fat, low-protein (LFLP) and HFHP meals with identical carbohydrate content, covered with identical insulin doses. On subsequent occasions, subjects repeated the HFHP meal with an adaptive model predictive insulin bolus until target postprandial glycemic control was achieved. RESULTS: With the same insulin dose, the HFHP increased the glucose incremental area under the curve over twofold (13,320 +/- 2,960 vs. 27,092 +/- 1,709 mg/dL ? min; P = 0.0013). To achieve target glucose control following the HFHP, 65% more insulin was required (range 17%-124%) with a 30%/70% split over 2.4 h. CONCLUSIONS: This study demonstrates that insulin dose calculations need to consider meal composition in addition to carbohydrate content and provides the foundation for new insulin-dosing algorithms to cover meals of varying macronutrient composition. PMID- 27388475 TI - Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study. AB - OBJECTIVE: Acylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODS: A population-based prospective study was conducted among 2,103 community-living Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTS: Over the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONS: A panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated. PMID- 27388477 TI - Ethical issues in preconception genetic carrier screening. AB - Population-based preconception genetic carrier screening programmes (PCS) with expanded panels are currently being developed in the Netherlands. This form of genetic screening for recessive traits differs from other forms of genetic testing and screening in that it is offered to persons not known to have an increased risk of being carriers of genetic traits for severe recessive diseases and in that they include tests for a large number of traits, potentially several hundred. This raises several ethical issues around justice, consequences, and autonomy. It will be argued that most of these ethical problems call for cautious reflection when setting up PCS and similar programmes within preconception care. It is moreover argued that it is ethically problematic to have an official aim and failing to mention possibly legitimate public aims that actually drive the development of PCS. PMID- 27388476 TI - Epigenetic silencing of serine protease HTRA1 drives polyploidy. AB - BACKGROUND: Increased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, and chromosomal instability are frequently observed characteristics of cancer cells. While some aspects of these events and the checkpoint mechanisms are well studied, not all players have yet been identified. As the role of proteases other than the proteasome in tumorigenesis is an insufficiently addressed question, we investigated the epigenetic control of the widely conserved protease HTRA1 and the phenotypes of deregulation. METHODS: Mouse embryonal fibroblasts and HCT116 and SW480 cells were used to study the mechanism of epigenetic silencing of HTRA1. In addition, using cell biological and genetic methods, the phenotypes of downregulation of HTRA1 expression were investigated. RESULTS: HTRA1 is epigenetically silenced in HCT116 colon carcinoma cells via the epigenetic adaptor protein MBD2. On the cellular level, HTRA1 depletion causes multiple phenotypes including acceleration of cell growth, centrosome amplification and polyploidy in SW480 colon adenocarcinoma cells as well as in primary mouse embryonic fibroblasts (MEFs). CONCLUSIONS: Downregulation of HTRA1 causes a number of phenotypes that are hallmarks of cancer cells suggesting that the methylation state of the HtrA1 promoter may be used as a biomarker for tumour cells or cells at risk of transformation. PMID- 27388479 TI - Abnormal white matter integrity in rapists as indicated by diffusion tensor imaging. AB - BACKGROUND: Recent research has documented structural brain abnormalities in various criminal offenders. However, there have been few brain imaging studies of sex offenders, and none on white matter integrity. The current study tested the hypothesis that rapists, when compared to matched controls, would show abnormal cortical and subcortical white matter integrity. RESULTS: Rapists showed significantly increased fractional anisotropy in the internal capsul e in the thalamus, caudate, and globus pallidus, and also in white matter tracts near the angular gyrus, posterior cingulate, frontal pole, lateral occipital cortex, and genu compared to controls matched for age, gender, and educational status. Reduced fractional anisotropy was observed in rapists in the posterior cingulum and in the inferior fronto-occipital fasciculus. CONCLUSIONS: To our knowledge, this is the first study indicating white matter abnormalities in rapists. Findings indicate abnormalities in white matter connectivity in brain regions involved in reward/motivation and moral judgment, which may predispose rapists to be both over-responsive to sexual reward stimuli and also to make inappropriate moral decisions. PMID- 27388481 TI - Smoking Is a Risk Factor for Severe Acute Kidney Injury in Hantavirus-Induced Nephropathia Epidemica. AB - BACKGROUND/AIMS: Hantaviruses are zoonotic pathogens causing emerging diseases worldwide. Patients typically present with fever, acute kidney injury (AKI) and thrombocytopenia. Puumala virus (PUUV) that causes nephropathia epidemica (NE) is common in Germany. Recently, a study from Finland revealed an association between nicotine consumption and the severity of AKI in NE. Differences between individuals in Finland and Germany might modulate the effect; therefore, the aim of our study was to prove that smoking is a risk factor for a severe course of NE in Germany. METHODS: A cross-sectional prospective survey of 485 patients with hantavirus infections was performed. Clinical and laboratory data during the acute course of the disease were obtained from medical reports and files, while follow-up (including smoking status) data were collected prospectively. RESULTS: Smoking information was available for 298 out of 485 patients (61%). Male was the predominant gender (67%), median age at the time of diagnosis was 50 (interquartile range, IQR 41-60) years and 34% of patients were current smokers during the phase of acute NE. Patients in the smoking group were significantly younger than in the non-smoking group (p < 0.0001). Peak serum creatinine levels were significantly higher in the smoking group than in the non-smoking patients (median 301 (IQR 186-469 MUmol/l) vs. median 240 (IQR 137-469 MUmol/l), p < 0.05). In addition, severe AKI (stages 2 and 3 using KDIGO criteria) was more common in current smokers (80%) than in the non-smokers (68%, p < 0.05). CONCLUSION: Current smoking is a risk factor for severity of AKI in patients with acute PUUV infection in Germany. Therefore, information about smoking habits needs to be an integral part of the documentation in patients with suspected acute PUUV infection, and increased monitoring of kidney function should be done in NE patients who are current smokers. PMID- 27388480 TI - Mapping surface residues of eIF5A that are important for binding to the ribosome using alanine scanning mutagenesis. AB - The translation elongation factor eIF5A is conserved through evolution and is necessary to rescue the ribosome during translation elongation of polyproline containing proteins. Although the site of eIF5A binding to the ribosome is known, no systematic analysis has been performed so far to determine the important residues on the surface of eIF5A required for ribosome binding. In this study, we used clustered charged-to-alanine mutagenesis and structural modeling to address this question. We generated four new mutants of yeast eIF5A: tif51A-4, tif51A-6, tif51A-7 and tif51A-11, and complementation analysis revealed that tif51A-4 and tif51A-7 could not sustain cell growth in a strain lacking wild-type eIF5A. Moreover, the allele tif51A-4 also displayed negative dominance over wild-type eIF5A. Both in vivo GST-pulldowns and in vitro fluorescence anisotropy demonstrated that eIF5A from mutant tif51A-7 exhibited an importantly reduced affinity for the ribosome, implicating the charged residues in cluster 7 as determinant features on the eIF5A surface for contacting the ribosome. Notably, modified eIF5A from mutant tif51A-4, despite exhibiting the most severe growth phenotype, did not abolish ribosome interactions as with mutant tif51A-7. Taking into account the modeling eIF5A + 80S + P-tRNA complex, our data suggest that interactions of eIF5A with ribosomal protein L1 are more important to stabilize the interaction with the ribosome as a whole than the contacts with P-tRNA. Finally, the ability of eIF5A from tif51A-4 to bind to the ribosome while potentially blocking physical interaction with P-tRNA could explain its dominant negative phenotype. PMID- 27388478 TI - Frontotemporal function]al connectivity and executive functions contribute to episodic memory performance. AB - The contributions of hemispheric-specific electrophysiology (electroencephalogram or EEG) and independent executive functions (inhibitory control, working memory, cognitive flexibility) to episodic memory performance were examined using abstract paintings. Right hemisphere frontotemporal functional connectivity during encoding and retrieval, measured via EEG alpha coherence, statistically predicted performance on recency but not recognition judgments for the abstract paintings. Theta coherence, however, did not predict performance. Likewise, cognitive flexibility statistically predicted performance on recency judgments, but not recognition. These findings suggest that recognition and recency operate via separate electrophysiological and executive mechanisms. PMID- 27388482 TI - The effect of statin therapy on plaque regression following acute coronary syndrome: a meta-analysis of prospective trials. AB - OBJECTIVE: To investigate the effect of statins on plaque regression after acute coronary syndrome (ACS). METHODS: We carried out a meta-analysis to assess the change in plaque and plaque components in patients with ACS under statin therapy. This meta-analysis combined data of 1623 participants from eight randomized controlled trials and seven observational studies. RESULTS: The benefits of high intensity statin therapy on plaque regression occurred after 6 months [standardized mean difference (SMD): -0.27; 95% confidence interval (CI): -0.43 to -0.12; P=0.0006] and were sustained over 12 months (SMD: -0.14; 95% CI: -0.25 to -0.03; P=0.01). No significant decrease was observed in the plaque volume and percent plaque volume under low-dose statin treatment. After 6 months of intensive statin treatment, the plaque volume reduced significantly in patients whose follow-up LDL cholesterol levels did (SMD: -0.16; 95% CI: -0.29 to -0.03; P=0.02) or did not (SMD: -0.21; 95% CI: -0.32 to -0.09; P=0.0007) decrease to 70 mg/dl or less. There was no significant change in plaque composition volumes, but an increase was found in the percent dense calcium volume of 1.31% (95% CI: 0.55 2.07%; P=0.0007). CONCLUSION: Intensive statin therapy duration over 6 months may be as important as achieved LDL-C of less than or equal to 70 mg/dl in plaque regression following ACS. Intensive statin treatment may lead to an earlier regression compared with low-dose statin therapy. PMID- 27388483 TI - Parent-child talk about the origins of living things. AB - This study examined relations between 124 British children's and their parents' endorsements about the origins of three living things (human, non-human animal, and plant) as reported on questionnaires. In addition to completing questionnaires, half of the sample discussed the origins of entities (n=64) in parent-child dyads before completing the questionnaires. The 7-year-old age group endorsed creationism more than evolution, and the 10-year-old age group endorsed both concepts equally for all three living things. Children's endorsements were correlated with their parents' endorsements for all three living things. Children's endorsement of evolutionary theory was more closely related to parent child conversational mentions of evolution than to parents' endorsement of evolutionary theory in questionnaires. A similar pattern was found for children's endorsement of creationism. Parent-child conversations did not consistently invoke evolution or creationism even when parents endorsed a particular theory. Findings are interpreted in relation to the pivotal role of joint collaborative conversation in children's appropriation of scientific content. PMID- 27388484 TI - Diagnosis of pneumothorax without exposure to ionising radiation. PMID- 27388485 TI - A surprising cause of polycythaemia. PMID- 27388486 TI - Deciphering clinical phenotypes in acute viral lower respiratory tract infection: Bronchiolitis is not an island. PMID- 27388487 TI - Accuracy of FENO for diagnosing asthma: a systematic review. AB - BACKGROUND: Measurement of FENO might substitute bronchial provocation for diagnosing asthma. We aimed to investigate the diagnostic accuracy of FENO measurement compared with established reference standard. METHODS: Systematic review and diagnostic meta-analysis. Data sources were Medline, Embase and Scopus up to 29 November 2015. Sensitivity and specificity were estimated using a bivariate model. Additionally, summary receiver-operating characteristic curves were estimated. RESULTS: 26 studies with 4518 participants (median 113) were included. Risk of bias was considered low for six of seven items in five studies and for five items in seven studies. The overall sensitivity in the meta-analysis was 0.65 (95% CI 0.58 to 0.72), the overall specificity 0.82 (0.76 to 0.86), the diagnostic OR 9.23 (6.55 to 13.01) and the area under the curve 0.80 (0.77 to 0.85). In meta-regression analyses, higher cut-off values were associated with increasing specificity (OR 1.46 per 10 ppb increase in cut-off) while there was no association with sensitivity. Sensitivities varied significantly within the different FENO devices, but not specificities. Neither prevalence, age, use of bronchoprovocation in >90% of participants or as exclusive reference standard test, nor risk of bias were significantly associated with diagnostic accuracy. CONCLUSIONS: There appears to be a fair accuracy of FENO for making the diagnosis of asthma. The overall specificity was higher than sensitivity, which indicates a higher diagnostic potential for ruling in than for ruling out the diagnosis of asthma. PMID- 27388488 TI - Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model. AB - BACKGROUND: The knowledge of where particles deposit in the respiratory tract is crucial for understanding the health effects associated with inhaled drug particles. METHOD: An ex vivo study was conducted to assess regional deposition patterns (thoracic vs. extrathoracic) of radioactive polydisperse aerosols with different size ranges [0.15 MUm-0.5 MUm], [0.25 MUm-1 MUm] and [1 MUm-9 MUm]. SPECT/CT analyses were performed complementary in order to assess more precisely the regional deposition of aerosols within the pulmonary tract. Experiments were set using an original respiratory tract model composed of a human plastinated head connected to an ex vivo porcine pulmonary tract. The model was ventilated by passive expansion, simulating pleural depressions. Aerosol was administered during nasal breathing. RESULTS: Planar scintigraphies allowed to calculate the deposited aerosol fractions for particles in the three size ranges from sub micron to micron The deposited fractions obtained, for thoracic vs. extra thoracic regions respectively, were 89 +/- 4 % vs. 11 +/- 4 % for [0.15 MUm-0.5 MUm], 78 +/- 5 % vs. 22 +/- 5 % for [0.25 MUm-1 MUm] and 35 +/- 11 % vs.65 +/- 11 % for [1 MUm-9 MUm]. CONCLUSION: Results obtained with this new ex vivo respiratory tract model are in good agreement with the in vivo data obtained in studies with baboons and humans. PMID- 27388489 TI - A Novel Method and Its Application to Measuring Pathogen Decay in Bioaerosols from Patients with Respiratory Disease. AB - This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique, cough aerosols were sampled from two persons with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Measurements and cultures from aerosol ages of 10, 20, 40, 900 and 2700 seconds were used to determine the optimum droplet nucleus size for pathogen transport and the airborne bacterial biological decay. The droplet nuclei containing the greatest number of colony forming bacteria per unit volume of airborne sputum were between 1.5 and 2.6 MUm. Larger nuclei of 3.9 MUm, were more likely to produce a colony when impacted onto growth media, because the greater volume of sputum comprising the larger droplet nuclei, compensated for lower concentrations of bacteria within the sputum of larger nuclei. Although more likely to produce a colony, the larger droplet nuclei were small in number, and the greatest numbers of colonies were instead produced by nuclei from 1.5 to 5.7 MUm. Very few colonies were produced by smaller droplet nuclei, despite their very large numbers. The concentration of viable bacteria within the dried sputum comprising the droplet nuclei exhibited an orderly dual decay over time with two distinct half-lives. Nuclei exhibiting a rapid biological decay process with a 10 second half-life were quickly exhausted, leaving only a subset characterized by a half life of greater than 10 minutes. This finding implied that a subset of bacteria present in the aerosol was resistant to rapid biological decay and remained viable in room air long enough to represent an airborne infection risk. PMID- 27388490 TI - Medical dispatchers recognise substantial amount of acute stroke during emergency calls. AB - BACKGROUND: Immediate recognition of stroke symptoms is crucial to ensure timely access to revascularisation therapy. Medical dispatchers ensure fast admission to stroke facilities by prioritising the appropriate medical response. Data on medical dispatchers' ability to recognise symptoms of acute stroke are therefore critical in organising emergency stroke care. We aimed to describe the sensitivity and positive predictive value of medical dispatchers' ability to recognise acute stroke during emergency calls, and to identify factors associated with recognition. METHODS: This was an observational study of 2653 consecutive unselected patients with a final diagnosis of stroke or transient ischemic attack (TIA). All admitted through the Emergency Medical Services Copenhagen, during a 2 year study period (2012-2014). Final diagnoses were matched with dispatch codes from the Emergency Medical Dispatch Centre. Sensitivity and positive predictive value were calculated. The effect of age, gender, and time-of-day was analysed using multivariable logistic regression. RESULTS: The sensitivity was 66.2 % (95 % CI: 64.4 %-68.0 %), and the positive predictive value was 30.2 % (95 % CI: 29.1 %-31.4 %). The multivariable logistic regression analyses showed that emergency calls during daytime and a final diagnosis of TIA vs. intracerebral haemorrhage (ICH), was positively associated with recognition of stroke (OR 2.70, 95 % CI: 2.04-3.57). DISCUSSION: This study reports a high rate of stroke recognition compared to other studies ranging from 31% to 74%. The high sensitivity is likely the result of a profound reorganisation of the Emergency Medical ServicesCopenhagen, including the introduction of EMDs with a medical profession, and a criteria-based dispatch tool. A recognition rate of 100 % is not obtainable without an inappropriate amount of false positive cases. CONCLUSIONS: We report an overall high recognition of stroke by medical dispatchers. A final diagnosis of TIA, compared to ICH, was positively associated with recognition of acute stroke. Emergency medical dispatchers serve as the essential first step in ensuring fast-track stroke treatment, which would promote timely acute therapy. TRIAL REGISTRATION: Unique identifier: NCT02191514. PMID- 27388491 TI - Pharmacokinetics and pharmacodynamics evaluation of a thermosensitive chitosan based hydrogel containing liposomal doxorubicin. AB - In situ gelling thermosensitive hydrogel formulation has been reported to effectively sustain the release of macromolecules for a long time. However, the low-molecular-weight hydrophilic drugs, such as doxorubicin (DOX), are not suitable for intratumoral injection because the release will complete within one day. In this study, liposomal doxorubicin (LipDOX) was added into the hydrogel to form a novel thermosensitive formulation which prolonged the sustained release of DOX. DOX+C/GP (doxorubicin in chitosan/beta-glycerophosphate) was prepared to compare with LipDOX+C/GP (liposomal doxorubicin in chitosan/beta-glycerophosphate hydrogel). The particle size of DOX-loaded liposome was 94.2nm and the encapsulation efficiency of DOX was near 98%. In vitro release experiments, the release of DOX in both DOX+C/GP group and LipDOX+C/GP group increased along with the increasing pH of buffers. However, the LipDOX+C/GP group with lower initial burst release had a much longer releasing duration than DOX+C/GP group (21days vs. 24h). In vitro and in vivo antitumor experiments demonstrated that LipDOX+C/GP group had better antineoplastic effect and less toxicity than DOX+C/GP group. Pharmacokinetics study showed LipDOX+C/GP exhibited a higher AUC0 t and longer MRT than DOX+C/GP in blood and tumor, which indicated that LipDOX+C/GP obtained an enhanced antitumor activity compared with DOX+C/GP. In addition, the lower distribution index (the ratio of AUC of normal tissue/AUC of tumor tissue) of the LipDOX+C/GP implied it had lower toxicity to normal tissues than DOX+C/GP. Therefore, the novel thermosensitive hydrogel formulation was potential for clinical application in cancer treatment. PMID- 27388492 TI - Motor imagery training enhances motor skill in children with DCD: A replication study. AB - BACKGROUND: Children with impaired motor coordination (or DCD) have difficulty using motor imagery. We have suggested that this difficulty is explained by the internal modeling deficit (IMD) hypothesis of DCD. Our previous training study lent support for this hypothesis by showing that a computerized imagery training protocol (involving action observation, and mental- and overt-rehearsal) was equally effective to perceptual-motor therapy (PMT) in promoting motor skill acquisition. AIMS: The study presented here was designed to replicate and extend this finding, targeting a select group of children with moderate-to-severe DCD. METHODS AND PROCEDURES: All 36 children with DCD who participated were referred to the study and scored below the 10th percentile for their age on the Movement Assessment Battery for Children (MABC). Using a randomized control trial, the referred children were assigned randomly to one of three groups using a blocked procedure: imagery training, perceptual-motor training (PMT), and wait-list control. Motor proficiency was measured using the MABC, pre and post-training. Individual training consisted of 60-min sessions, conducted once a week for 5 weeks. RESULTS: Results showed that the imagery protocol was equally effective as PMT in promoting motor skill acquisition, with moderate-to-large effect sizes. Individual differences showed that the majority of children in the two intervention groups improved their motor performance significantly. CONCLUSIONS: Overall, these results further support the use of motor imagery protocols in the treatment of DCD, and tentative support for the IMD hypothesis. Developmental and dose issues in the implementation of imagery-based intervention are discussed. PMID- 27388494 TI - Aripiprazole for the treatment of irritability and aggression in children and adolescents affected by autism spectrum disorders. AB - INTRODUCTION: Aripiprazole is an atypical antipsychotic approved for the treatment of irritability and aggression in children and adolescents aged 6-17 years with autism spectrum disorder. AREAS COVERED: This review will discuss the drug profile as well as available studies of aripiprazole in individuals with autism spectrum disorder as documented in prospective randomized controlled trials. Expert commentary: The heterogeneity of autism spectrum disorder has implications for assessing the effectiveness and safety of aripiprazole as it may not produce the same results in two individuals with the same diagnosis but different etiologies. Subgrouping of patients according to their overall presentation of symptoms may therefore be warranted. In addition, consideration should be given to the potential causes of irritability and aggression, such as coexisting medical conditions and environmental factors including inappropriate intervention of parents and teachers. In these cases, the identification of the underlying cause is important because the appropriate management. PMID- 27388493 TI - A new screening method for periodontitis: an alternative to the community periodontal index. AB - BACKGROUND: Periodontal screening plays an important role in the prevention of periodontal disease and promotes an improvement in oral health-related quality of life. The World Health Organization's Community Periodontal Index should be carried out by well-trained dentists. However, the Community Periodontal Index is an invasive technique, and if used for periodontal screening, increases the cost of evaluation. In order to overcome these issues, we developed saliva tests for periodontal screening. The purpose of this study was to calculate the sensitivity and specificity of our method for measuring hemoglobin and lactate dehydrogenase levels in saliva. METHODS: Inclusion criteria were adults aged over 20 years with at least 20 teeth remaining. The study population comprised 38 men and 54 women with a mean age of 50.03 years. Oral examinations were carried out by dentists, and the number of remaining teeth, presence or absence of calculus, bleeding on probing and pocket depth were recorded. In this study, periodontitis was defined according to the criteria of the Center for Disease Control and Prevention in partnership with the American Academy of Periodontology. In order to examine hemoglobin and lactate dehydrogenase levels in saliva, participants were instructed to chew on a standard-sized tasteless and odorless gum base for 5 min, during which time, stimulated whole saliva was continuously collected. RESULTS: The sensitivity and specificity for hemoglobin levels were 0.759 and 0.763, respectively, and 0.722 and 0.711, respectively, for lactate dehydrogenase levels. Combining these two tests, when samples tested positive for both hemoglobin and lactate dehydrogenase, the positive predictive value was 91.7 %. CONCLUSION: Measuring hemoglobin and lactate dehydrogenase levels in saliva is a less invasive method than the Community Periodontal Index. Therefore, our saliva tests may be a viable alternative to the Community Periodontal Index for periodontal screening. PMID- 27388495 TI - Gastro-oesophageal reflux in large-sized, deep-chested versus small-sized, barrel chested dogs undergoing spinal surgery in sternal recumbency. AB - OBJECTIVE: The aim of this study was to investigate whether an increased frequency of gastro-oesophageal reflux (GOR) is more common in large-sized, deep chested dogs undergoing spinal surgery in sternal recumbency than in small-sized, barrelchested dogs. STUDY DESIGN: Prospective, cohort study. ANIMALS: Nineteen small-sized, barrel-chested dogs (group B) and 26 large-sized, deep-chested dogs (group D). METHODS: All animals were premedicated with intramuscular (IM) acepromazine (0.05 mg kg-1) and pethidine (3 mg kg-1) IM. Anaesthesia was induced with intravenous sodium thiopental and maintained with halothane in oxygen. Lower oesophageal pH was monitored continuously after induction of anaesthesia. Gastro oesophageal reflux was considered to have occurred whenever pH values > 7.5 or < 4 were recorded. If GOR was detected during anaesthesia, measures were taken to avoid aspiration of gastric contents into the lungs and to prevent the development of oesophagitis/oesophageal stricture. RESULTS: The frequency of GOR during anaesthesia was significantly higher in group D (6/26 dogs; 23.07%) than in group B (0/19 dogs; 0%) (p = 0.032). Signs indicative of aspiration pneumonia, oesophagitis or oesophageal stricture were not reported in any of the GOR cases. CONCLUSIONS AND CLINICAL RELEVANCE: In large-sized, deep-chested dogs undergoing spinal surgery in sternal recumbency, it would seem prudent to consider measures aimed at preventing GOR and its potentially devastating consequences (oesophagitis/oesophageal stricture, aspiration pneumonia). PMID- 27388497 TI - Illusory line motion in onset and offset bars. AB - Illusory line motion (ILM) refers to the perception of motion in a bar that is presented all at once next to an inducing stimulus. The experimental methods for producing and quantifying ILM are varied, and the resulting explanations are likewise at odds. The current study examined the explanations for ILM away from the inducing stimulus (bright or dark flash) using bars that either suddenly appear (onset bars) or suddenly disappear (offset bars). Real motion is used to cancel ILM, providing three measures to quantify ILM: the consistency of responding to only ILM in the absence of real motion; the distance between the points of subjective equality between ILM and the real motion; and the area between the curves relating perception of motion to the real and illusory conditions. ILM quantities for onset and offset bars are strongly correlated when the bar change occurs after the flash. However, onset bars presented during the flash do not show any evidence of ILM, whereas offset bars removed during the flash result in reverse ILM (rILM). Moreover, rILM and ILM are not correlated, suggesting they reflect two separate illusions. These results are consistent over the various measures of ILM. PMID- 27388498 TI - Geographical Analysis for Detecting High-Risk Areas for Bovine/Human Rabies Transmitted by the Common Hematophagous Bat in the Amazon Region, Brazil. AB - BACKGROUND: The common hematophagous bat, Desmodus rotundus, is one of the main wild reservoirs of rabies virus in several regions in Latin America. New production practices and changed land use have provided environmental features that have been very favorable for D. rotundus bat populations, making this species the main transmitter of rabies in the cycle that involves humans and herbivores. In the Amazon region, these features include a mosaic of environmental, social, and economic components, which together creates areas with different levels of risk for human and bovine infections, as presented in this work in the eastern Brazilian Amazon. METHODOLOGY: We geo-referenced a total of 175 cases of rabies, of which 88% occurred in bovines and 12% in humans, respectively, and related these cases to a number of different geographical and biological variables. The spatial distribution was analyzed using the Kernel function, while the association with independent variables was assessed using a multi-criterion Analytical Hierarchy Process (AHP) technique. FINDINGS: The spatiotemporal analysis of the occurrence of rabies in bovines and humans found reduction in the number of cases in the eastern state of Para, where no more cases were recorded in humans, whereas high infection rates were recorded in bovines in the northeastern part of the state, and low rates in the southeast. The areas of highest risk for bovine rabies are found in the proximity of rivers and highways. In the case of human rabies, the highest concentration of high-risk areas was found where the highway network coincides with high densities of rural and indigenous populations. CONCLUSION: The high-risk areas for human and bovine rabies are patchily distributed, and related to extensive deforested areas, large herds of cattle, and the presence of highways. These findings provide an important database for the generation of epidemiological models that could support the development of effective prevention measures and controls. PMID- 27388496 TI - Central attention is serial, but midlevel and peripheral attention are parallel-A hypothesis. AB - In this brief review, we argue that attention operates along a hierarchy from peripheral through central mechanisms. We further argue that these mechanisms are distinguished not just by their functional roles in cognition, but also by a distinction between serial mechanisms (associated with central attention) and parallel mechanisms (associated with midlevel and peripheral attention). In particular, we suggest that peripheral attentional deployments in distinct representational systems may be maintained simultaneously with little or no interference, but that the serial nature of central attention means that even tasks that largely rely on distinct representational systems will come into conflict when central attention is demanded. We go on to review both the behavioral and neural evidence for this prediction. We conclude that even though the existing evidence mostly favors our account of serial central and parallel noncentral attention, we know of no experiment that has conclusively borne out these claims. As such, this article offers a framework of attentional mechanisms that will aid in guiding future research on this topic. PMID- 27388499 TI - Emergency Department-Based Care Transitions for Pediatric Patients: A Systematic Review. AB - CONTEXT: Successful care transitions between emergency departments (EDs) and outpatient settings have implications for quality, safety, and cost of care. OBJECTIVE: To investigate the effectiveness of ED-based care transition interventions in achieving outpatient follow-up among pediatric patients. DATA SOURCES: Medline, Embase, CINAHL, Cochrane Library, trial registers, and reference lists of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Eligible studies included randomized controlled trials of ED-based care transition interventions involving pediatric patients (aged <=18 years). Study selection, data extraction, and risk of bias assessment were performed in duplicate and independent manner. Study results were pooled for meta-analysis by using a random effects model. RESULTS: Sixteen randomized controlled trials, comprising 3760 patients, were included in the study. Most interventions were single-site (n = 14), multicomponent (n = 12), and focused on patients with asthma (n = 8). Pooling data from 10 studies (n = 1965 patients) found moderate quality evidence for a relative increase of 29% in outpatient follow-up with interventions compared with routine care (odds ratio, 1.58 [95% confidence interval, 1.08-2.31]). Successful interventions included structured telephone reminders, educational counseling on follow-up, and appointment scheduling assistance. There was low-quality evidence when pooling data from 5 studies (n = 1609 participants) that exhibited little or no beneficial effect of interventions on ED readmissions (risk ratio, 1.02 [95% confidence interval, 0.91-1.15]). LIMITATIONS: All studies were conducted in urban US hospitals which makes generalization of the results to rural settings and other countries difficult. CONCLUSIONS: ED-based care transition interventions are effective in increasing follow-up but do not seem to reduce ED readmissions. Further research is required to investigate the mechanisms that affect the success of these interventions. PMID- 27388500 TI - Newborn Resuscitation Training in Resource-Limited Settings: A Systematic Literature Review. AB - CONTEXT: Birth asphyxia contributes substantially to neonatal mortality in low- and middle-income countries (LMICs). The effects of training birth attendants in neonatal resuscitation (NR) on mortality are limited by falloff of skills and knowledge over time and transference of learned skills into clinical practice. OBJECTIVE: This review examined acquisition and retention of NR knowledge and skills by birth attendants in LMICs and the effectiveness of interventions to improve them. DATA SOURCES: Medline, Cochrane, Embase, CINAHL, Bireme, and African Index Medicus databases were searched. We reviewed Web pages and reports from non-peer-reviewed (or "gray") literature sources addressing NR training in LMICs. STUDY SELECTION: Articles on acquisition and retention of NR knowledge and skills, and interventions to improve them, were limited to LMICs. RESULTS: The initial search identified 767 articles, of which 45 met all inclusion criteria. Of these, 31 articles analyzed acquisition of knowledge and skills, and 19 analyzed retention. Most studies found high acquisition rates, although birth attendants struggled to learn bag-mask ventilation. Although significant falloff of knowledge and skills occurred after training, refresher training seemed to improve retention. Results of the gray literature analysis suggest that formal, structured practice sessions improve retention. LIMITATIONS: This review did not analyze training's direct impact on mortality. CONCLUSIONS: Knowledge and skills falloff is a significant barrier to the success of NR training programs and possibly to reducing newborn mortality in LMICs. Refresher training and structured practice show significant promise. Additional research is needed to implement and assess retention improvement strategies in classroom and clinical settings. PMID- 27388501 TI - Structural transformation in monolayer materials: a 2D to 1D transformation. AB - Reducing the dimensions of materials to atomic scales results in a large portion of atoms being at or near the surface, with lower bond order and thus higher energy. At such scales, reduction of the surface energy and surface stresses can be the driving force for the formation of new low-dimensional nanostructures, and may be exhibited through surface relaxation and/or surface reconstruction, which can be utilized for tailoring the properties and phase transformation of nanomaterials without applying any external load. Here we used atomistic simulations and revealed an intrinsic structural transformation in monolayer materials that lowers their dimension from 2D nanosheets to 1D nanostructures to reduce their surface and elastic energies. Experimental evidence of such transformation has also been revealed for one of the predicted nanostructures. Such transformation plays an important role in bi-/multi-layer 2D materials. PMID- 27388502 TI - Hepatitis C Therapy in Renal Patients: Who, How, When? AB - Renal patients are overexposed to hepatitis C virus (HCV) infection. Hepatitis C virus infection may induce renal disease, i.e., cryoglobulinemic membrano proliferative glomerulopathy and non-cryoglobulinemic nephropathy. Hepatitis C virus impacts general outcomes in chronic kidney disease, dialysis or transplanted patients. Hepatitis C virus infection is now about to be only part of their medical history thanks to new direct acting antiviral drugs exhibiting as much as over 95% of sustained virological response. All HCV-infected patients potentially can receive the treatment. Control of the virus is associated with better outcomes in all cases, whatever the severity of the hepatic or renal disease. This article focuses on HCV-induced renal diseases, the reciprocal impact of HCV infection on the renal outcome and renal status in liver disease, use of new direct-acting antiviral drugs with dosage adaptations and the most recent safety data. PMID- 27388504 TI - Dynamics and Hydrodynamics of Molecular Superrotors. AB - In recent years, several femtosecond laser techniques have been developed that can make gas molecules rotate extremely fast, whereas the gas stays translationally cold. Herein we use molecular-dynamics simulations to investigate the collisional dynamics of gases of such molecules ("superrotors"). We found that the common route of superrotors to equilibrium is rather generic. It starts with a long-lasting "gyroscopic stage", during which the molecules keep their fast rotation and the orientation of their angular momentum despite the many collisions they undergo. The inhibited rotational relaxation is characterized by a persistent anisotropy in the molecular angular distribution, manifested in long lasting optical birefringence and in anisotropic diffusion of the gas. Later, the gyroscopic stage is abruptly terminated by a self-accelerating explosive rotational-translational energy exchange that generates sound and macroscopic vortices with a hot rotating core. PMID- 27388503 TI - Retinal Image Enhancement Using Robust Inverse Diffusion Equation and Self Similarity Filtering. AB - As a common ocular complication for diabetic patients, diabetic retinopathy has become an important public health problem in the world. Early diagnosis and early treatment with the help of fundus imaging technology is an effective control method. In this paper, a robust inverse diffusion equation combining a self similarity filtering is presented to detect and evaluate diabetic retinopathy using retinal image enhancement. A flux corrected transport technique is used to control diffusion flux adaptively, which eliminates overshoots inherent in the Laplacian operation. Feature preserving denoising by the self-similarity filtering ensures a robust enhancement of noisy and blurry retinal images. Experimental results demonstrate that this algorithm can enhance important details of retinal image data effectively, affording an opportunity for better medical interpretation and subsequent processing. PMID- 27388505 TI - Correction: Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy. AB - [This corrects the article DOI: 10.1371/journal.pone.0044709.]. PMID- 27388506 TI - A new floating piezoelectric microphone for the implantable middle ear microphone in experimental studies. AB - CONCLUSIONS: The new floating piezoelectric microphone is feasible for use as an implantable middle ear microphone in a totally implantable cochlear implant. OBJECTIVES: A piezoelectric sensor that is driven by the acoustic vibration of the ossicles is one possible design for a microphone for a totally implantable cochlear implant. Such a new floating piezoelectric microphone has been manufactured in the lab. The purpose of this article was to study the frequency response of the new floating piezoelectric microphone in the intact ossicular chain and to identify whether it is usable and implantable. METHODS: The frequency response of the new floating piezoelectric microphone was analyzed using in vitro testing of fresh cadaveric heads. The microphone, which was designed with an integrated unibody structure to ensure good biocompatibility and capsulation, was attached to the long process of the incus by a titanium clip, or placed in the tympanic cavity and stimulated with pure tones of different frequencies. RESULTS: The new floating piezoelectric microphone can pick up the vibration of the long process of the incus and convert it into electrical signals sensitively and flatly. PMID- 27388507 TI - Temporal Informative Analysis in Smart-ICU Monitoring: M-HealthCare Perspective. AB - The rapid introduction of Internet of Things (IoT) Technology has boosted the service deliverance aspects of health sector in terms of m-health, and remote patient monitoring. IoT Technology is not only capable of sensing the acute details of sensitive events from wider perspectives, but it also provides a means to deliver services in time sensitive and efficient manner. Henceforth, IoT Technology has been efficiently adopted in different fields of the healthcare domain. In this paper, a framework for IoT based patient monitoring in Intensive Care Unit (ICU) is presented to enhance the deliverance of curative services. Though ICUs remained a center of attraction for high quality care among researchers, still number of studies have depicted the vulnerability to a patient's life during ICU stay. The work presented in this study addresses such concerns in terms of efficient monitoring of various events (and anomalies) with temporal associations, followed by time sensitive alert generation procedure. In order to validate the system, it was deployed in 3 ICU room facilities for 30 days in which nearly 81 patients were monitored during their ICU stay. The results obtained after implementation depicts that IoT equipped ICUs are more efficient in monitoring sensitive events as compared to manual monitoring and traditional Tele-ICU monitoring. Moreover, the adopted methodology for alert generation with information presentation further enhances the utility of the system. PMID- 27388508 TI - Community diagnosis by a family survey: an exposure to primary care during medical undergraduate training. PMID- 27388510 TI - Sexual Disorders in Men and Iranian Ancient Medicine. PMID- 27388509 TI - Association of pre-operative medication use with post-operative delirium in surgical oncology patients receiving comprehensive geriatric assessment. AB - BACKGROUND: Older patients undergoing surgery tend to have a higher frequency of delirium. Delirium is strongly associated with poor surgical outcomes. This study evaluated the association between pre-operative medication use and post-operative delirium (POD) in surgical oncology patients receiving comprehensive geriatric assessment (CGA). METHODS: A total of 475 patients who were scheduled for cancer surgery and received CGA from January 2014 to June 2015 were included. Pre operative medication review through CGA was conducted on polypharmacy (>=5 medications), delirium-inducing medications (DIMs), fall-inducing medications (FIMs), and potentially inappropriate medications (PIMs). POD was confirmed by psychiatric consultation, and DSM-V criteria were used for diagnosing delirium. The model fit of the prediction model was assessed by computing the Hosmer Lemeshow goodness-of-fit test. Effect size was measured using the Nagelkerke R(2). Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC). RESULTS: Two models were constructed for multivariate analysis based on univariate analysis; model I included dementia and DIM in addition to age and sex, and model II included PIM instead of DIM of model I. Every one year increase of age increased the risk of POD by about 1.1-fold. DIM was a significant factor for POD after adjusting for confounders (AOR 12.78, 95 % CI 2.83-57.74). PIM was also a significant factor for POD (AOR 5.53, 95 % CI 2.03-15.05). The Hosmer-Lemeshow test results revealed good fits for both models (chi(2) = 3.842, p = 0.871 for model I and chi(2) = 8.130, p = 0.421 for model II). The Nagelkerke R(2) effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R(2)effect size of 0.174 and AUROC of 0.819. CONCLUSIONS: These results suggest that pharmacists' comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients. PMID- 27388511 TI - Does Viewing Pornography Reduce Marital Quality Over Time? Evidence from Longitudinal Data. AB - Numerous studies have examined the connection between pornography viewing and marital quality, with findings most often revealing a negative association. Data limitations, however, have precluded establishing directionality with a representative sample. This study is the first to draw on nationally representative, longitudinal data (2006-2012 Portraits of American Life Study) to test whether more frequent pornography use influences marital quality later on and whether this effect is moderated by gender. In general, married persons who more frequently viewed pornography in 2006 reported significantly lower levels of marital quality in 2012, net of controls for earlier marital quality and relevant correlates. Pornography's effect was not simply a proxy for dissatisfaction with sex life or marital decision-making in 2006. In terms of substantive influence, frequency of pornography use in 2006 was the second strongest predictor of marital quality in 2012. Interaction effects revealed, however, that the negative effect of porn use on marital quality applied to husbands, but not wives. In fact, post-estimation predicted values indicated that wives who viewed pornography more frequently reported higher marital quality than those who viewed it less frequently or not at all. The implications and limitations of this study are discussed. PMID- 27388512 TI - Mapping the Zambian prison health system: An analysis of key structural determinants. AB - Health and health service access in Zambian prisons are in a state of 'chronic emergency'. This study aimed to identify major structural barriers to strengthening the prison health systems. A case-based analysis drew on key informant interviews (n = 7), memos generated during workshops (n = 4) document review and investigator experience. Structural determinants were defined as national or macro-level contextual and material factors directly or indirectly influencing prison health services. The analysis revealed that despite an favourable legal framework, four major and intersecting structural factors undermined the Zambian prison health system. Lack of health financing was a central and underlying challenge. Weak health governance due to an undermanned prisons health directorate impeded planning, inter-sectoral coordination, and recruitment and retention of human resources for health. Outdated prison infrastructure simultaneously contributed to high rates of preventable disease related to overcrowding and lack of basic hygiene. These findings flag the need for policy and administrative reform to establish strong mechanisms for domestic prison health financing and enable proactive prison health governance, planning and coordination. PMID- 27388513 TI - Biosynthesis of (2)H-Labeled Phenylalanine by a New Methylotrophic Mutant Brevibacterium methylicum. AB - The biosynthesis of (2)H-labeled phenylalanine was done by converse of low molecular weight substrates ([U-(2)H]methanol and (2)H2O) in a new RuMP facultative methylotrophic mutant Brevibacterium methylicum. To make the process work, adapted cells with improved growth characteristics were used on minimal medium M9 with the maximum content of (2)H-labeled substrates. Alanine, valine, and leucine/isoleucine were produced and accumulated exogeneously in addition to the main product of biosynthesis. Electron impact mass spectrometry of methyl esters of the N-Dns-amino acid mixture obtained after the chemical derivatization of growth medium with dansyl chloride and diazomethane, was done to calculate the deuterium enrichment of the amino acids synthesized. The experimental data testified to the character of labeling of amino acid molecules as heterogeneous; however, high levels of deuterium enrichment were detected in all presented molecules-for phenylalanine the enrichment was six, leucine/isoleucine-five, valine-five, and alanine-three deuterium atoms. PMID- 27388514 TI - Correlation of Polar Lipid Composition with 16S rRNA Phylogeny in Methanogens. Further Analysis of Lipid Component Parts. AB - Qualitative analyses of lipid component parts (core lipids, phospholipid-polar head groups, and glycolipid-sugar moieties) without separation of individual lipids were done for further 14 strains of methanogens. The results confirmed the conclusion of our previous paper (System. Appl. Microbiol. 16, 342 1993) that the distribution of lipid component parts was characteristic to taxonomic groups of methanogens at a family or genus level. Our previous and present analyses of lipid component part distribution of methanogens supported the division of the order Methanomicrobiales into two new orders Methanomicrobiales and "Methanosarcinales" proposed by Boone et al. based on 16S rRNA analyses (Methanogenesis: Ecology, Physiology, Biochemistry, & Genetics, 1993, pp 35-80). The whole results also phenotypically supported the establishment of new families "Methanocaldococcaceae" and "Methanosaetaceae" and new genera "Methanothermococcus", "Methanocaldococcus", "Methanoignis", and "Methanosalsus" proposed by Boone et al. PMID- 27388515 TI - Alanine Racemase from an Acidophile, Acidiphilium organovorum: Purification and Characterization. AB - An alanine racemase (EC 5.1.1.1) from an acidophilic heterotrophic bacterium, Acidiphilium organovorum 13H, was purified and characterized. The enzyme had a dimeric structure with identical subunits of M r 33,000 each. Although A. organovorum 13H is an acidophile, the enzyme had its maximum velocity at pH 9, corresponding to its location in the cytoplasm. Activity was maximum between 50 and 60 degrees C. For an enzyme from a mesophile, it was stable to heat, showing no loss of activity after a 30-min incubation at 65 degrees C. The enzyme needed pyridoxal 5'-phosphate (PLP) as a cofactor for its activity, as seen from the loss of activity upon dialysis against PLP-free buffer containing hydroxylamine and its absorption maximum at 420 nm. Activity was ihhibited by common inhibitors of PLP-dependent enzymes. PLP content studies found that 1 mole of enzyme contained 2 moles of PLP. The enzyme catalyzed the symmetric reversible racemization of alanine exclusively. PMID- 27388516 TI - Interaction between Potato Starch and Sucrose-lipid Monoesters Studied by Differential Scanning Calorimetry. AB - The formation and dissociation of complexes composed of potato starch and sucrose lipid monoesters (SE: monocaprate, monolaurate, monomyristate, monopalmitate, and monostearate) were studied by differential scanning calorimetry (DSC). The formation and dissociation temperatures of each complex increased as the number of carbon atoms in the alkyl chain of SE increased, and as the content of starch increased, overlapping with the gelatinization temperature. Therefore, the DSC curves for starch gelatinization differed according to the added SE and water content. The completion temperature for the dissociation of each starch-SE complex depended on the water content, similar to that for the gelatinization of starch. The heat of fusion of the starch-SE (monopalmitate) complex obtained from the completion temperature was nearly twice that of the original starch, 140 kJ/mol glucose unit. It is suggested that a stable conformation of each complex was not formed during the gelatinization of the starch granules, but during cooling from a temperature higher than the dissociation temperature of the complex which had formed during the gelatinization process. PMID- 27388517 TI - Continuous Hydrolysis of Pectate by Immobilized Endo-polygalacturonase in a Continuously Stirred Tank Reactor. AB - Enzymatic hydrolysis of pectate was carried out continuously to produce pectate oligosaccharides by immobilized endo-polygalacturonase in a continuous stirred tank reactor (CSTR) with high efficiency. The enzyme was immobilized on to chitosan beads by the absorption method, and the reaction was performed with an initial pectate concentration of 10 gl(-1) at 35 degrees C and pH 4.0 at a dilution rate of 0.87-2.8 h(-1). The hydrolysis products mainly consisted of mono , di-, tri-, tetra-, penta-, hexa- and heptasaccharides, with the highest conversion being 0.78. A higher volumetric production rate of the total hydrolyzate, which was dependent on the dilution rate, was obtained than that by a batch reaction. The hydrolysis process was mathematically modeled from the basic material balance and rate equations, and showed agreement between the simulated and experimental results. This reactor system was found to be effective for obtaining pectate oligosaccharides with a high production rate. PMID- 27388518 TI - Generation of Nitric Oxide from Spin-trapping Agents under Oxidative Conditions. AB - Nitric oxide (NO) generation from the spin-trapping agents, phenyl-tert butylnitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) and 5,5 dimethyl-1-pyrroline N-oxide (DMPO), under UV irradiation in the presence of dissolved oxygen and by oxidation with the Fenton reagent was examined by using ESR spin-trapping and spectrophotometric methods. A triplet signal at g=2.041 was observed after the ferrous complex of dithiocarbamate [Fe(MGD)2] had been added to a solution of these trapping agents treated with UV irradiation and the Fenton reagent, showing that NO was trapped with Fe(MGD)2. The concentration of nitrite induced from NO was determined via the Griess reaction to increase with the time of the treatment. It is speculated by reference to the ESR signal observed at the position around g=2.006 that the C=N double bond might have been cleaved by oxidation, resulting in the formation of a nitroso compound, and that NO was then generated by the fission of the C-N bond of the nitroso compound. NO generated in this way activated guanylate cyclase, from which it can be expected that a spin trapping agent acts as an NO generator in vivo as well as a free radical scavenger. PMID- 27388519 TI - Influence of Phytate Removal and Structural Modification on the Calcium-binding Properties of Soybean Globulins. AB - The calcium-binding properties of soybean globulins that have been deamidated or enzymatically hydrolyzed after the removal of phytate were physicochemically investigated. The level of calcium was reduced from 0.32% to 0.013% and that of phosphorus was reduced from 1.1% to 0.050% by treating with cation- and anion exchange resins. The calcium-binding properties of soybean globulins were described by the Langmuir equation, the maximum amount of bound calcium (N) and the affinity parameter for calcium (K) being obtained for each sample. The value of N was decreased by the removal of phytate, while the deamidation caused the value of N to increase. As hydrolysis proceeded, the value of N increased to a degree of hydrolysis of 32%, and then decreased. Based on this result, there seems to be an optimum molecular weight of hydrolyzed soybean globulins for the amount of bound calcium. In addition, the value of K for every soybean globulin sample was much lower than that of phytic acid, indicating that the globulins had proper calcium-binding properties for calcium absorption in the small intestine. PMID- 27388520 TI - Protein Disulfide Isomerase Activity of Some Plant Seeds. AB - The activity of protein disulfide isomerase, in the extracts of several dormant seeds including soybean, rice, wheat, and maize was assayed. The activity was higher in the extracts of beans than in those of the other seeds. A correlation was significant (R=0.95 and 0.93; p<0.01) between the PDI activity and the concentration of protein soluble in a salt solution. PMID- 27388521 TI - Lack of Light/Dark Regulation of Enzymes Involved in the Photosynthetic Carbon Reduction Cycle in Cyanobacteria, Synechococcus PCC 7942 and Synechocystis PCC 6803. AB - During the photosynthetic carbon reduction (PCR) cycle of Synechococcus PCC 7942 and Synechocystis PCC 6803, fructose-1,6-bisphosphatase, NADP(+)-glyceraldehyde-3 phosphate dehydrogenase, and ribulose-5-phosphate kinase were not sensitive to treatment with dithiothreitol (DTT), a reducing agent, in vitro and were not regulated by light in vivo, unlike the chloroplastic enzymes of higher plants. These results indicate that the PCR cycle in the cyanobacterial cells may not be actually regulated by light in vivo even if the ferredoxin/thioredoxin system is present. PMID- 27388522 TI - Syntheses of Highly Oxygen-functionalized Derivatives of Dihydrodihydroxyphthalic Acid in Enantiomerically Enriched Forms. AB - Starting from dihydrodihydroxyphthalic acid (DDP), (1R, 2S, 5R, 6S)-(-)-3,4 bis(benzyloxymethyl)-5-hydroxy-8,8-dimethyl-6,8-dioxabicyclo[4.3.0]non-3-en-2-yl chloroacetate (>95%e.e.), a highly oxygen-functionalized derivative, was prepared by a combination of chemical and enzymatic reactions. The key step for asymmetrization was hydrolysis of the corresponding meso bis-chloroacetate with pig pancreatic lipase. PMID- 27388523 TI - Purification and Properties of Three beta-N-Acetylglucosaminidases from Lactobacillus casei ATCC 27092. AB - Three beta-N-acetylglucosaminidases, GlcNAcase A, B, and C, were purified from the culture fluid of Lactobacillus casei ATCC 27092, and the molecular weights of these enzymes were estimated to be 54,000, 51,000, and 44,000, respectively, by SDS-PAGE. The production of these GlcNAcases was accelerated by the addition of N acetylglucosamine to the culture. These enzymes had pIs of about 5.2, an optimum pH of 5.0-5.5, and an optimum temperature of 37-40 degrees C. The K m values of GlcNAcase A, B, and C for p-nitrophenyl-beta-N-acetylglucosamine were 0.85, 1.30, and 1.04 mM and those for p-nitrophenyl-beta-N-acetylgalactosamine were 39.6, 57.7, and 60.8 mM, respectively. PMID- 27388524 TI - Corrigendum to 'The MLN4924 inhibitor exerts a neuroprotective effect against oxidative stress injury via Nrf2 protein accumulation' [Redox Biol. 8 (2016) 341 347]. PMID- 27388525 TI - Antidiabetic effect of chitosan oligosaccharide (GO2KA1) is mediated via inhibition of intestinal alpha-glucosidase and glucose transporters and PPARgamma expression. AB - We have previously reported that administration of low molecular weight chitosan oligosaccharide (GO2KA1) significantly suppressed postprandial blood glucose rise with increased plasma adiponectin and HbA1c levels in animals and humans. However, the cellular mechanisms whereby GO2KA1 exerts antihyperglycemic effects still remain to be determined. Using intestinal Caco-2 cells and 3T3-L1 cells, here we show that GO2KA1 has dual modes of antidiabetic action by (1) inhibiting intestinal alpha-glucosidase as well as glucose transporters SGLT1 and GLUT2 that were distinct from the acarbose effect; (2) enhancing adipocyte differentiation, PPARgamma expression and its target genes, such as FABP4, adiponectin, and GLUT4, whereas the effects were abolished by co-treatment with BADGE, a PPARgamma antagonist. Moreover, GO2KA1 significantly increased glucose uptake, which was reduced in the presence of BADGE. Our data show that GO2KA1 may prevent hyperglycemia by inhibiting intestinal glucose digestion and transport and also enhance glucose uptake, at least in part, by upregulating adiponectin expression through PPARgamma in adipocytes. These findings may provide potential molecular modes of action for the antidiabetic effects of chitosan oligosaccharide observed in clinical and animal studies. (c) 2016 BioFactors, 43(1):90-99, 2017. PMID- 27388526 TI - Time perception of simultaneous and sequential events in early-onset schizophrenia. AB - Timing disorders in schizophrenia are a well-known phenomenon. However, no studies have yet assessed the role of temporal distortions in early-onset schizophrenia (EOS), despite evidence that distorted time perception may share genetic risk factors with schizophrenia and may be a useful indicator in identifying individuals at risk for schizophrenia. In the present study, we investigated the ability of 10 patients with EOS (mean age = 21.5 years, SD = 6) matched with 20 healthy control participants (mean age = 25.3 years, SD = 4.6) in order to compare the durations of two visual events, presented either sequentially or overlapping in time, along with neuropsychological assessments of attention, working memory, and executive functions. Each participant had to judge a total of 336 stimuli. We found that temporal overlap had a greater negative effect on ability to judge the duration of a pair of stimuli in EOS patients than in healthy control participants. In addition, EOS patients showed impairments in attention and executive functions. Furthermore, in EOS patients, the scores for executive and attentional functions were significantly correlated with accuracy of temporal estimation in the overlap condition (r = 0.31, p < 0.05 and r = 0.57, p < 0.05, respectively). These preliminary results suggest that impairments in neuropsychological functions participate in the deficit in time estimation observed in patients with EOS. These conclusions highlight the importance of testing time perception in patients with EOS and could contribute to the development of cognitive remediation-based therapy for these patients. PMID- 27388527 TI - Changes in Central Aortic Pressure Levels, Wave Components and Determinants Associated with High Peripheral Blood Pressure States in Childhood: Analysis of Hypertensive Phenotype. AB - The aims were to determine whether children's high peripheral blood pressure states (HBP) are associated with increased central aortic blood pressure (BP) and to characterize hemodynamic and vascular changes associated with HBP in terms of changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR) and net and relative contributions of reflected waves to the aortic pulse amplitude. We included 154 subjects (mean age 11; range 4-16 years) assigned to one of two groups: normal peripheral BP (NBP, n = 101), defined as systolic and diastolic BP < 90th percentile, or high BP (HBP, n = 53), defined as average systolic and/or diastolic BP levels >=90th percentile (curves for sex, age and body height). The HBP group included children with hypertensive and pre-hypertensive BP levels. After a first analysis, groups were compared excluding obese and dyslipidemic children. Peripheral and central aortic BP, PWV and pulse wave-derived parameters (augmentation index, forward and backward wave components' amplitude) were measured using gold-standard techniques, applanation tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). Independent of the presence of dyslipidemia and/or obesity, aortic systolic and pulse BP were higher in HBP than in NBP children. The increase in central BP could not be explained by an increase in the relative contribution of reflections to the aortic pressure wave, higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP would be explained by an increase in the amplitude of both incident and reflected wave components. PMID- 27388528 TI - H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthritis. AB - BACKGROUND: Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA). We investigated the effect of H3K27me3 demethylase inhibition on chondrogenesis and assessed its utility in cartilage tissue engineering and in understanding cartilage destruction in OA. METHODS: We used a high-content screen to assess the effect of epigenetic modifying compounds on collagen output during chondrogenesis of monolayer human mesenchymal stem cells (MSCs). The impact of GSK-J4 on gene expression, glycosaminoglycan output and collagen formation during differentiation of MSCs into cartilage discs was investigated. Expression of lysine (K)-specific demethylase 6A (UTX) and Jumonji domain-containing 3 (JMJD3), the HEK27Me3 demethylases targeted by GSK-J4, was measured in damaged and undamaged cartilage from patients with OA. The impact of GSK-J4 on ex vivo cartilage destruction and expression of OA-related genes in human articular chondrocytes (HACs) was assessed. H3K27Me3 demethylase regulation of transforming growth factor (TGF)-beta-induced gene expression was measured in MSCs and HACs. RESULTS: Treatment of chondrogenic MSCs with the H3K27me3 demethylase inhibitor GSK-J4, which targets JMJD3 and UTX, inhibited collagen output; expression of chondrogenic genes, including SOX9 and COL2A1; and disrupted glycosaminoglycan and collagen synthesis. JMJD3 but not UTX expression was increased during chondrogenesis and in damaged OA cartilage, suggesting a predominant role of JMJD3 in chondrogenesis and OA. GSK-J4 prevented ex vivo cartilage destruction and expression of the OA-related genes MMP13 and PTGS2. TGF beta is a key regulator of chondrogenesis and articular cartilage homeostasis, and TGF-beta-induced gene expression was inhibited by GSK-J4 treatment of both chondrogenic MSCs and HACs. CONCLUSIONS: Overall, we show that H3K27me3 demethylases modulate chondrogenesis and that enhancing this activity may improve production of tissue-engineered cartilage. In contrast, targeted inhibition of H3K27me3 demethylases could provide a novel approach in OA therapeutics. PMID- 27388529 TI - Elucidating the pathophysiological significance of circulating omentin levels: Is higher better? PMID- 27388530 TI - Adalimumab (Humira) for the Treatment of Hidradenitis Suppurativa. AB - Adalimumab (Humira(r)) is a novel therapy approved by the US Food and Drug Administration, Health Canada, and the European Commission for the treatment of hidradenitis suppurativa (HS). Results of two Phase III trials of adalimumab demonstrate significantly higher efficacies compared to placebo. Primary efficacy outcome of 50% reduction in abscess and inflammatory nodule count was seen in 41.8% and 58.9% of participants receiving adalimumab in PIONEER I and PIONEER II studies, respectively, showing substantial improvement compared with placebo groups in both trials (26.0% and 27.6%, respectively). Although the significance of secondary efficacy measures of adalimumab every week treatment (EW) was not consistent between PIONEER I and PIONEER II studies, participants achieving abscess and inflammatory nodule counts of 0, 1, or 2 were significant (EW 51.8%) compared to placebo (32.2%) in the PIONEER II trial. Participants also demonstrated a marked decrease in skin pain measurements from baseline between EW patients (45.7%) and placebo (20.7%) in the PIONEER II trial. Modified Sartorius scores were decreased from baseline in both PIONEER I (-24.4) and PIONEER II ( 28.9) trials versus placebo (-15.7 and -9.5, respectively). Adverse events were mild to moderate and comparable between all treatment groups including placebo. Taken together, these data conclude that treatment of HS with adalimumab is a safe and effective therapy resulting in a significant decrease in abscess and inflammatory nodule counts within the first 12 weeks of treatment. PMID- 27388531 TI - Frontal Fibrosing Alopecia. AB - Frontal fibrosing alopecia, described just over 20 years ago, has become one of the most frequently seen causes of scarring alopecia at many specialist hair clinics. Considered a clinical variant of lichen planopilaris (LPP), it has distinctive features and associations which distinguish it from LPP. Although largely affecting postmenopausal women, a small but increasing number of men and premenopausal women are affected. The spectrum of the disease has expanded from involvement of the frontal hairline and eyebrows, to potentially affecting the entire hairline, facial and body hair. Genetic and environmental factors have been implicated but the aetiology remains uncertain. A range of treatments have been used in management of the condition, but clinical trials are required to establish effectiveness. PMID- 27388532 TI - Sustainable Nanotechnology: Opportunities and Challenges for Theoretical/Computational Studies. AB - For assistance in the design of the next generation of nanomaterials that are functional and have minimal health and safety concerns, it is imperative to establish causality, rather than correlations, in how properties of nanomaterials determine biological and environmental outcomes. Due to the vast design space available and the complexity of nano/bio interfaces, theoretical and computational studies are expected to play a major role in this context. In this minireview, we highlight opportunities and pressing challenges for theoretical and computational chemistry approaches to explore the relevant physicochemical processes that span broad length and time scales. We focus discussions on a bottom-up framework that relies on the determination of correct intermolecular forces, accurate molecular dynamics, and coarse-graining procedures to systematically bridge the scales, although top-down approaches are also effective at providing insights for many problems such as the effects of nanoparticles on biological membranes. PMID- 27388533 TI - A simplified calculation procedure for mass isotopomer distribution analysis (MIDA) based on multiple linear regression. AB - We have developed a novel, rapid and easy calculation procedure for Mass Isotopomer Distribution Analysis based on multiple linear regression which allows the simultaneous calculation of the precursor pool enrichment and the fraction of newly synthesized labelled proteins (fractional synthesis) using linear algebra. To test this approach, we used the peptide RGGGLK as a model tryptic peptide containing three subunits of glycine. We selected glycine labelled in two 13 C atoms (13 C2 -glycine) as labelled amino acid to demonstrate that spectral overlap is not a problem in the proposed methodology. The developed methodology was tested first in vitro by changing the precursor pool enrichment from 10 to 40% of 13 C2 -glycine. Secondly, a simulated in vivo synthesis of proteins was designed by combining the natural abundance RGGGLK peptide and 10 or 20% 13 C2 glycine at 1 : 1, 1 : 3 and 3 : 1 ratios. Precursor pool enrichments and fractional synthesis values were calculated with satisfactory precision and accuracy using a simple spreadsheet. This novel approach can provide a relatively rapid and easy means to measure protein turnover based on stable isotope tracers. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388534 TI - Study of angiogenic signaling pathways in hemangioblastoma. AB - Hemangioblastoma (HB) is mainly located in the brain and the spinal cord. The tumor is composed of two major components, namely neoplastic stromal cells and abundant microvessels. Thus, hyper-vascularization is the hallmark of this tumor. Despite the identification of germline and/or epigenetic mutations of Von Hippel Lindau (VHL) gene as an important pathogenic mechanism of HB, little is known about the molecular signaling involved in this highly vascularized tumor. The present study investigated the key players of multiple angiogenic signaling pathways including VEGF/VEGFR2, EphB4/EphrinB2, SDF1alpha/CXCR4 and Notch/Dll4 pathways in surgical specimens of 22 HB. The expression of key angiogenic factors was detected by RT2 -PCR and Western blot. Immunofluorescent staining revealed the cellular localization of these proteins. We demonstrated a massive upregulation of mRNA levels of VEGF and VEGFR2, CXCR4 and SDF1alpha, EphB4 and EphrinB2, as well as the main components of Dll4-Notch signaling in HB. An increase in the protein expression of VEGF, CXCR4 and the core-components of Dll4 Notch signaling was associated with an activation of Akt and Erk1/2 and accompanied by an elevated expression of PCNA. Immuofluorescent staining revealed the expression of VEGF and CXCR4 in endothelial cells as well as in tumor cells. Dll4 protein was predominantly found in tumor cells, whereas EphB4 immunoreactivity was exclusively detected in endothelial cells. We conclude that multiple key angiogenic pathways were activated in HB, which may synergistically contribute to the abundant vascularization in this tumor. Identification of these aberrant pathways provides potential targets for a possible future application of anti-angiogenic therapy for this tumor, particularly when a total surgical resection becomes difficult due to the localization or multiplicity of the tumor. PMID- 27388535 TI - Donor registries, first-person consent legislation, and the supply of deceased organ donors. AB - In this paper, we exploit the varied timing in state adoption of organ donor registries and first-person consent (FPC) legislation to examine corresponding changes in the supply of deceased organ donors. Results indicate that the establishment of a state organ donor registry leads to an increase in donation rates of approximately 8%, while the adoption of FPC legislation has no effect on the supply of organ donors. These results reinforce the need to encourage individuals to communicate their donation preferences, either explicitly via a registry or by discussing them with family. PMID- 27388536 TI - Timing of adding blood to prime affects inflammatory response to neonatal cardiopulmonary bypass. AB - Complications from systemic inflammation are reported in neonates following exposure to cardiopulmonary bypass. Although the use of asanguinous primes can reduce these complications, in neonates, this can result in significant haemodilution, requiring addition of blood. This study investigates whether the addition of blood after institution of bypass alters the inflammatory response compared with a blood prime. Neonatal swine were randomised into four groups: blood prime, blood after bypass but before cooling, blood after cooling but before low flow, and blood after re-warming. All groups were placed on central bypass, cooled, underwent low flow, and then re-warmed for a total bypass time of 2 hours. Although haematocrit values between groups varied throughout bypass, all groups ended with a similar value. Although they spent time with a lower haematocrit, asanguinous prime groups did not have elevated lactate levels at the end of bypass compared with blood prime. Asanguinous primes released less tumour necrosis factor alpha than blood primes (p=0.023). Asanguinous primes with blood added on bypass produced less interleukin 10 and tumour necrosis factor alpha (p=0.006, 0.019). Animals receiving blood while cool also showed less interleukin 10 and tumour necrosis factor alpha production than those that received blood warm (p=0.026, 0.033). Asanguinous primes exhibited less oedema than blood primes, with the least body weight gain noted in the end cool group (p=0.011). This study suggests that using an asanguinous prime for neonates being cooled to deep hypothermia is practical, and the later addition of blood reduces inflammation. PMID- 27388537 TI - "It's All About How You Carry Yourself About": How Medical Students Conceptualize Professionalism in Trinidad & Tobago. AB - : Phenomenon: This paper concerns itself with the value system that informs and motivates medical students of the twenty-first century as distinct from earlier cohorts. It notes a shift from an era of altruism within which the medical professional was a 'pillar of society' always 'on duty' and always concerned foremost for the patient to an era in which he/she is just another member of the work force, subject to public scrutiny and criticism, to patient autonomy and to a self-serving ethos which characterizes the present age. Whilst concerns have been raised for a continuing and separate morality of medicine, young professionals in other studies have cited a range of characteristics including honesty, trustworthiness and respect alongside competence and medical skill. However, the notion of 'performance' has made a strong thrust into the literature, with students citing the putting on and taking off of dual personae as part of their complex identity in this present time. They are entitled to their own lives, to drop the act and just be themselves when off duty, picking it back up again with the duty call. APPROACH: The present study then investigated the views on this subject of two groups of medical students in Trinidad & Tobago in the Caribbean, one made up entirely of nationals and one including students from other parts of the Caribbean and the USA. They discussed the topic in focus groups of eight; their responses were then analysed thematically and subject to discourse analysis. FINDINGS: The study revealed diverse attitudes with some embracing the ethical standards of a high calling that whilst others were concerned that too much was expected, that they had a right to break free and be themselves as long as they did not transgress too far from their expected roles. There were two distinct groups both concerned with 'how' they 'carried themselves about' but this meant different things to each dependent on which of the two perspectives they embraced. As a whole, the study revealed an ongoing conflict of value systems with concern for patient welfare just remaining uppermost. Insights: As The University of the West Indies has now stepped into the field of medical professionalism actively it would hope to support students in resolving their conflicts more consciously in response to the range of philosophical stances which currently present themselves. PMID- 27388538 TI - Reducing health inequities affecting immigrant women: a qualitative study of their available assets. AB - BACKGROUND: Immigrant women often experience health inequities, whether for reasons of gender, country of origin, or socioeconomic status. The view of immigrant women has always focussed on their needs, without taking into account their available assets. A salutogenic approach incorporating an assets analysis could provide a new perspective on the design of health promotion interventions to reduce health inequities. The study objective was to identify the assets of this group of women as a necessary first step in changing the paradigm used in such health promotion interventions. METHODS: This qualitative study combined focus groups, in-depth interviews, and a photovoice session. The aim was to describe the assets of this group, based on Antonovsky's salutogenic approach and assets model. Qualitative results were interpreted with a phenomenological focus, identifying each individual's internal, community, and institutional assets. RESULTS: The self awareness of skills was linked to a person's description of herself as being optimistic, having religious beliefs, and having motivations and objectives in life, for herself, her family or her children. Being motivated helped the women to persist in doing or learning things that could be useful in confronting difficult situations. Another selfawareness skill was feeling useful to others, whether this was due to religious beliefs about their role in life or to the importance of the mutual support of interpersonal relationships. CONCLUSIONS: High optimism, strong capacity for struggle and self-initiative, the importance of religious beliefs, social support, and concern for their children's future were described as assets of immigrant women. Identification of these assets allows us to develop more in-depth knowledge and better tools for health promotion programs and policies intended to reduce health inequities in this population of immigrant women. PMID- 27388539 TI - Health at the borders: Bayesian multilevel analysis of women's malnutrition determinants in Ethiopia. AB - BACKGROUND: Women's malnutrition, particularly undernutrition, remains an important public health challenge in Ethiopia. Although various studies examined the levels and determinants of women's nutritional status, the influence of living close to an international border on women's nutrition has not been investigated. Yet, Ethiopian borders are regularly affected by conflict and refugee flows, which might ultimately impact health. OBJECTIVE: To investigate the impact of living close to borders in the nutritional status of women in Ethiopia, while considering other important covariates. DESIGN: Our analysis was based on the body mass index (BMI) of 6,334 adult women aged 20-49 years, obtained from the 2011 Ethiopian Demographic and Health Survey (EDHS). A Bayesian multilevel multinomial logistic regression analysis was used to capture the clustered structure of the data and the possible correlation that may exist within and between clusters. RESULTS: After controlling for potential confounders, women living close to borders (i.e. <=100 km) in Ethiopia were 59% more likely to be underweight (posterior odds ratio [OR]=1.59; 95% credible interval [CrI]: 1.32-1.90) than their counterparts living far from the borders. This result was robust to different choices of border delineation (i.e. <=50, <=75, <=125, and <=150 km). Women from poor families, those who have no access to improved toilets, reside in lowland areas, and are Muslim, were independently associated with underweight. In contrast, more wealth, higher education, older age, access to improved toilets, being married, and living in urban or lowlands were independently associated with overweight. CONCLUSIONS: The problem of undernutrition among women in Ethiopia is most worrisome in the border areas. Targeted interventions to improve nutritional status in these areas, such as improved access to sanitation, economic and livelihood support, are recommended. PMID- 27388540 TI - Point-of-care platelet function testing to predict blood loss after coronary artery bypass grafting surgery: a prospective observational pilot study. AB - AIM: With an increase in the number of patients who are on antiplatelet medications until the day of surgery, we undertook a prospective observational study to assess the ability of thromboelastography, thromboelastography platelet mapping and aggregometry via multiplate to detect platelet dysfunction and predict blood loss following coronary artery bypass grafting (CABG) surgery. METHODS: Platelet function was evaluated pre- and post-cardiopulmonary bypass via thromboelastography, thromboelastography platelet mapping and aggregometry via multiplate in 52 patients undergoing coronary artery bypass grafting surgery. The median chest tube drainage of all patients in the study was ascertained to stratify patients into two groups: patients with and those without evidence of excessive blood loss after cardiac surgery. RESULTS: Although all modalities could detect a decrease in platelet function following cardiopulmonary bypass, univariate and multivariate regression analysis identified preoperative arachidonic acid and adenosine diphosphate testing via multiplate as independent predictors of bleeding after cardiac surgery. Receiver operating curves on these multiplate parameters showed an area under the curve of 0.68 (p=0.03) and 0.66 (p=0.01) for arachidonic acid and adenosine diphosphate assays, respectively. CONCLUSION: This pilot study shows that preoperative multiplate testing may be a better predictor of platelet dysfunction and the resultant blood loss following cardiac surgery. PMID- 27388541 TI - Preventing medication errors. PMID- 27388542 TI - Medium-term durability of giant hiatus hernia repair without mesh. AB - Introduction This is the second report on objective review of 100 patients who underwent composite fundoplication-cardiopexy for repair of giant hiatus hernia (GHH) at a median of 24 months following surgery. Outcomes were objective follow up by endoscopy and quality of life (QoL) by Gastrointestinal Quality of Life Index (GIQLI), modified Visick scores and dysphagia scores. The initial report for this cohort suggested a low objective recurrence rate (9%) and substantial improvements in QoL indices. Methods The rate of hernia recurrence was assessed with Kaplan-Meier analysis and covariates were analysed with the Cox proportional hazards model. Paired t-tests and related samples Wilcoxon signed-rank tests were used to compare QoL scores. Unpaired data were compared with the independent samples t-test and Mann-Whitney U test. Results Objective review was obtained in 97% of the patients. There were five recurrences of hernias that had a vertical height of >2cm from the diaphragmatic hiatus, with three patients requiring reoperation for severe dysphagia. Small recurrences (<2cm) occurred in 20 patients. The median time to recurrence was 40 months (95% confidence interval: 34-46 months). At two years, recurrence of any size had occurred in 24% of cases. At follow-up review (median: 27 months), the mean GIQLI score was 109 (p=0.279), the median modified Visick score was 2 (p=0.954) and the median dysphagia score was 41 (p=0.623). There was no evidence that the GIQLI score (p=0.089), the modified Visick score (p=0.339) or the dysphagia score (p=0.445) changed significantly after recurrence. Conclusions There was a sustained improvement in overall QoL and reflux scores after GHH repair. QoL scores showed persistent improvement in reflux and overall health, even in the subgroup with recurrence. The majority (80%) of recurrences were small and recurrent herniation did not appear to significantly change QoL. The rates of recurrence and QoL are comparable with those for other methods of repair. PMID- 27388543 TI - Routes of early enteral nutrition following oesophagectomy. AB - Introduction Oesophagectomy for cancer is a challenging procedure with a five year overall survival rate of 15-20%. Early enteral nutrition following oesophagectomy is a crucial component of the postoperative recovery and carries a significant impact on the outcome. Different methods of enteral feeding were conducted in our unit. The aim of this study was to examine the efficacy and safety of nasojejunal tube (NJT), jejunostomy tube (JT) and pharyngostomy tube (PT) feeding after oesophagectomy. Methods A retrospective review was carried out of prospectively collected data on patients with oesophageal cancer who underwent an oesophagectomy between 2011 and 2014. The primary outcome was feeding tube related complications such as occlusion, dislocation and leak. The secondary outcomes were length of stay and 30-day morbidity. Results A total of 90 oesophagectomies were included in the study. A NJT was inserted in 41 patients (45.6%), a JT was used in 14 patients (15.5%) and a PT was the route for enteral nutrition in 35 patients (38.9%). In total, five patients (5.5%) developed tube related complications. There were no tube related complications in the NJT group but one JT patient (7.1%) developed tube related cellulitis (p=0.189) and four PT patients (11.4%) developed tube related haemorrhage (p=0.544), tube dislocation (p=0.544) or cellulitis (p=0.189). The median length of stay and 30-day postoperative morbidity were similar between the groups. Conclusions NJT feeding is a less invasive, feasible route for early enteral nutrition following oesophagectomy. A randomised controlled trial is recommended to verify these findings. PMID- 27388544 TI - Dobutamine stress echocardiography resulting in acute gastric dilatation and pneumoporta. AB - Acute gastric dilatation is a rare cause of gas within the hepatic portal vein, but one that is important to recognise as prompt decompression via a nasogastric tube is usually successful in resolving the situation. We report the rare case of a 68-year-old man with spontaneous acute gastric dilatation 50 minutes after a dobutamine stress echo that resulted in pneumoporta. The patient had a Nissen's fundoplication 18 months previously; patients with previous antireflux surgery or who have a degree of gastric outlet obstruction may be at increased risk of this unusual condition. Conservative management, with placement of a nasogastric tube was successful in resolving his symptoms. PMID- 27388545 TI - Chylopericardium presenting as cardiac tamponade secondary to mediastinal lymphangioma. AB - Mediastinal lymphangioma is a rare entity and chylopericardium is a rare form of pericardial effusion. We report a case of acute chylous cardiac tamponade due to a cervicomediastinal lymphangioma in a one-year-old boy. A chest x-ray revealed marked cardiac enlargement and echocardiography showed massive pericardial effusion. Emergency surgery was performed whereby a pericardial window was created, followed by excision of the lymphangioma. PMID- 27388546 TI - Hemilaminectomy for large spinal extradural meningeal cysts: A case report and review of surgical techniques. AB - Spinal extradural meningeal cysts (SEMC) are uncommon causes of back pain. The literature contains only case reports of this pathology, and treatment remains controversial due to its rarity. We present a case of SEMC and describe an approach via hemilaminectomy, with the choice of side guided by radiological imaging, followed by complete excision of the cyst and repair of the underlying dural defect. PMID- 27388547 TI - Recurrent laryngeal nerve palsy due to displacement of a gastric band. AB - The left recurrent laryngeal nerve is at increased risk of compression by oesophageal pathology due to its long course through the neck and thorax. Here we report a case of left vocal cord palsy secondary to displacement of a gastric band, resulting in oesophageal dilatation and neuropraxia of the left recurrent laryngeal nerve. Vocal cord function partially improved following removal of the gastric band. PMID- 27388548 TI - Preparation and characterisation of the colistin-entrapped liposome driven by electrostatic interaction for intravenous administration. AB - Potential use of liposome for polycationic colistin is hindered by their phospholipid membrane permeability. In this study, liposomes were modified with sodium cholesteryl sulphate (Chol-SO4(-)) for improving the colistin loading by enhancing the colistin-bilayer electrostatic attraction. We have evaluated two liposomes: colistin-entrapped liposome of Chol-SO4(-) (CCL) and coated Chol-SO4( )/colistin complex liposome (CCCL). In comparison with CCL which formed large aggregates at Chol-SO4(-)/colistin charge ratio below 2:1, CCCL showed a smaller size less dependent on the charge ratio, probably arising from more colistin entrapped on the inner leaflet of bilayer. Both liposomes exhibited significantly increased entrapment efficiency as compared with the liposome without Chol-SO4( ). But colistin released upon dilution, implying free transfer of colistin through bilayers. Pharmacokinetics results showed the approximately four-fold increase in the plasma AUC0-8 h for CCCL and CCL as compared with colistin solution, showing potential benefit for infectious target localisation by prolonging the systemic circulation of colistin. PMID- 27388549 TI - Paramagnetic Structures within a Microfluidic Channel for Enhanced Immunomagnetic Isolation and Surface Patterning of Cells. AB - In this report, we demonstrate a unique method for embedding magnetic structures inside a microfluidic channel for cell isolation. We used a molding process to fabricate these structures out of a ferrofluid of cobalt ferrite nanoparticles. We show that the embedded magnetic structures significantly increased the magnetic field in the channel, resulting in up to 4-fold enhancement in immunomagnetic capture as compared with a channel without these embedded magnetic structures. We also studied the spatial distribution of trapped cells both experimentally and computationally. We determined that the surface pattern of these trapped cells was determined by both location of the magnet and layout of the in-channel magnetic structures. Our magnetic structure embedded microfluidic device achieved over 90% capture efficiency at a flow velocity of 4 mm/s, a speed that was roughly two orders of magnitude faster than previous microfluidic systems used for a similar purpose. We envision that our technology will provide a powerful tool for detection and enrichment of rare cells from biological samples. PMID- 27388551 TI - Editorial Comment. PMID- 27388550 TI - Bee venom phospholipase A2 ameliorates motor dysfunction and modulates microglia activation in Parkinson's disease alpha-synuclein transgenic mice. AB - alpha-Synuclein (alpha-Syn) has a critical role in microglia-mediated neuroinflammation, which leads to the development of Parkinson's disease (PD). Recent studies have shown that bee venom (BV) has beneficial effects on PD symptoms in human patients or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin-induced PD mice. This study investigated whether treatment with BV-derived phospholipase A2 (bvPLA2) would improve the motor dysfunction and pathological features of PD in human A53T alpha-Syn mutant transgenic (A53T Tg) mice. The motor dysfunction of A53T Tg mice was assessed using the pole test. The levels of alpha-Syn, microglia and the M1/M2 phenotype in the spinal cord were evaluated by immunofluorescence. bvPLA2 treatment significantly ameliorated motor dysfunction in A53T Tg mice. In addition, bvPLA2 significantly reduced the expression of alpha-Syn, the activation and numbers of microglia, and the ratio of M1/M2 in A53T Tg mice. These results suggest that bvPLA2 could be a promising treatment option for PD. PMID- 27388552 TI - Author Reply. PMID- 27388553 TI - Nonalcoholic Fatty Liver Disease: Epidemiology, Natural History, and Diagnostic Challenges. PMID- 27388554 TI - Preparative scale and convenient synthesis of a water-soluble, deep cavitand. AB - Cavitands are established tools of supramolecular chemistry and molecular recognition, and they are finding increasing application in sensing and sequestration of physiologically relevant molecules in aqueous solution. The synthesis of a water-soluble, deep cavitand is described. The route comprises six (linear) steps from commercially available precursors, and it relies on the fourfold oligomeric cyclization reaction of resorcinol with 2,3-dihydrofuran that leads to the formation of a shallow resorcinarene framework; condensation with aromatic panels, which deepens the hydrophobic binding cavity; construction of rigid urea functionalities on the upper rim; and the introduction of the water solubilizing methylimidazolium groups on the lower rim. Late intermediates of the synthesis can be used in the preparation of congener cavitands with different properties and applications, and a sample of such a synthetic procedure is included in this protocol. Emphasis is placed on scaled-up reactions and on purification procedures that afford materials in high yield and avoid chromatographic purification. This protocol provides improvements over previously described procedures, and it enables the preparation of sizable amounts of deep cavitands: 7 g of a water-soluble cavitand can be prepared from resorcinol in 13 working days. PMID- 27388555 TI - Rapid and simple isolation of vascular, epidermal and mesophyll cells from plant leaf tissue. AB - To understand physiological phenomena at the tissue level, elucidation of tissue specific molecular functions in vivo is required. As an example of the current state of affairs, many genes in plants have been reported to have discordant levels of expression between bulk tissues and the specific tissues in which the respective gene product is principally functional. The principal challenge in deciphering such tissue-specific functions lies in separating tissues with high spatiotemporal resolution to evaluate accurate gene expression profiles. Here, we provide a simple and rapid tissue isolation protocol to isolate all three major leaf tissues (mesophyll, vasculature and epidermis) from Arabidopsis within 30 min with high purity. On the basis of the different cell-to-cell connectivities of tissues, the mesophyll isolation is achieved by making protoplasts, and the vasculature and epidermis isolation is achieved through sonication and enzymatic digestion of leaves. We have successfully tested the protocol on several other plant species, including crop plants such as soybean, tomato and wheat. Furthermore, isolated tissues can be used not only for tissue-specific transcriptome assays but also potentially for tissue-specific proteome and methylome assays. PMID- 27388556 TI - Laboratory breeding of the short-lived annual killifish Nothobranchius furzeri. AB - Turquoise killifish, Nothobranchius furzeri, have an intrinsically short life span, with a median life span of <6 months and a maximum (90%) life span of 9 months. This short life span, which is unique among vertebrates, evolved naturally and has resulted in N. furzeri becoming a widely used laboratory model species in aging research and other disciplines. Here, we describe a protocol for the maintenance and breeding of the species under laboratory conditions. We provide details for egg incubation, hatching, everyday care of juvenile and adult fish, breeding and treatment of most common diseases. Emphasis is given to the fact that the requirements of N. furzeri substantially differ from those of other fish model taxa; N. furzeri live brief lives and in nature undergo nonaquatic embryo development, with consequences for their laboratory culture. PMID- 27388557 TI - Post-licensure safety surveillance study of routine use of tetanus toxoid, reduced diphtheria toxoid and 5-component acellular pertussis vaccine. AB - An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults. PMID- 27388558 TI - Controllable light capsules employing modified Bessel-Gauss beams. AB - We report, in theory and experiment, on a novel class of controlled light capsules with nearly perfect darkness, directly employing intrinsic properties of modified Bessel-Gauss beams. These beams are able to naturally create three dimensional bottle-shaped region during propagation as long as the parameters are properly chosen. Remarkably, the optical bottle can be controlled to demonstrate various geometries through tuning the beam parameters, thereby leading to an adjustable light capsule. We provide a detailed insight into the theoretical origin and characteristics of the light capsule derived from modified Bessel Gauss beams. Moreover, a binary digital micromirror device (DMD) based scheme is first employed to shape the bottle beams by precise amplitude and phase manipulation. Further, we demonstrate their ability for optical trapping of core shell magnetic microparticles, which play a particular role in biomedical research, with holographic optical tweezers. Therefore, our observations provide a new route for generating and controlling bottle beams and will widen the potentials for micromanipulation of absorbing particles, aerosols or even individual atoms. PMID- 27388559 TI - Human mesenchymal stromal cell-enhanced osteogenic differentiation by contact interaction with polyethylene terephthalate nanogratings. AB - Among the very large number of polymeric materials that have been proposed in the field of orthopedics, polyethylene terephthalate (PET) is one of the most attractive thanks to its flexibility, thermal resistance, mechanical strength and durability. Several studies have been proposed that interface nano- or micro structured surfaces with mesenchymal stromal cells (MSCs), demonstrating the potential of this technology for promoting osteogenesis. All these studies were carried out on biomaterials other than PET, which remains almost uninvestigated in terms of cell shaping, alignment and differentiation. Here, we study the effect of PET 350-depth nanogratings (NGs) with a ridge and lateral groove size of 500 nm (T1) or 1 MUm (T2), on bone marrow-derived human MSC (hMSC) differentiation in relation to the osteogenic fate. We demonstrate that these substrates, especially T2, can promote the osteogenic phenotype more efficiently than standard flat surfaces and that this effect is more marked if cells are cultured in osteogenic medium than in basal medium. Finally, we show that the shape and disposition of calcium hydroxyapatite granules on the different substrates was influenced by the substrate symmetry, being more elongated and spatially organized on NGs than on flat surfaces. PMID- 27388560 TI - Nurse-physician collaboration in an academic medical centre: The influence of organisational and individual factors. AB - Ineffective physician-nurse collaboration has been recognised to adversely impact patient and organisational outcomes, and some studies suggest an underlying factor may be that nurses and physicians have different perceptions of interprofessional collaboration (IPC). The objectives of this study were to evaluate for a difference in the perception of IPC between physicians and nurses and to explore potential contributing factors at the individual and organisational levels to any observed difference. Data including measures of perceptions of IPC were collected from a convenience sample of resident physicians (n = 47), attending physicians (n = 18), and nurses (n = 54) providing care for internal medicine patients in a large tertiary care academic medical centre. Regression analysis revealed significantly lower perceptions of IPC scores for nurses in comparison to the scores of both the resident and attending physician groups (p = .0001 for both). Although demographic and workload factors also differed by profession, only profession and workload remained significant in regression analysis. Given the known relationships between effective physician nurse collaboration and superior patient and organisational outcomes, better defining the individual and organisational predictors of IPC scores may support development of more effective interventions targeting improvements in IPC. PMID- 27388561 TI - Income inequality and foregone medical care in Europe during The Great Recession: multilevel analyses of EU-SILC surveys 2008-2013. AB - BACKGROUND: The association between income inequality and societal performance has been intensely debated in recent decades. This paper reports how unmet need for medical care has changed in Europe during The Great Recession, and investigates whether countries with smaller income differences have been more successful than inegalitarian countries in protecting access to medical care during an economic crisis. METHODS: Six waves of EU-SILC surveys (2008-2013) from 30 European countries were analyzed. Foregone medical care, defined as self reported unmet need for medical care due to costs, waiting lists, or travel difficulties, was examined among respondents aged 30-59 years (N = 1.24 million). Countries' macro-economic situation was measured by Real Gross Domestic Product (GDP) per capita. The S80/S20 ratio indicated the country's level of income inequality. Equity issues were highlighted by separate analyses of disadvantaged respondents with limited economic resources and relatively poor health. Cross tabulations and multilevel linear probability regression models were utilized. RESULTS: Foregone medical care increased 2008-2013 in the majority of the 30 countries, especially among the disadvantaged parts of the population. For the disadvantaged, unmet need for medical care tended to be higher in countries with larger income inequalities, regardless of the average economic standard in terms of GDP per capita. Both for disadvantaged and for other parts of the samples, a decline in GDP had more severe effects on access in inegalitarian countries than in countries with less income inequality. CONCLUSIONS: During The Great Recession, unmet need for medical care increased in Europe, and social inequalities in foregone medical care widened. Overall, countries with a more egalitarian income distribution have been more able to protect their populations, and especially disadvantaged groups, against deteriorated access to medical care when the country is confronted with an economic crisis. PMID- 27388562 TI - Molecular Dynamics Simulations Reveal that Water Diffusion between Graphene Oxide Layers is Slow. AB - Membranes made of stacked layers of graphene oxide (GO) hold the tantalizing promise of revolutionizing desalination and water filtration if selective transport of molecules can be controlled. We present the findings of an integrated study that combines experiment and molecular dynamics simulation of water intercalated between GO layers. We simulated a range of hydration levels from 1 wt.% to 23.3 wt.% water. The interlayer spacing increased upon hydration from 0.8 nm to 1.1 nm. We also synthesized GO membranes that showed an increase in layer spacing from about 0.7 nm to 0.8 nm and an increase in mass of about 15% on hydration. Water diffusion through GO layers is an order of magnitude slower than that in bulk water, because of strong hydrogen bonded interactions. Most of the water molecules are bound to OH groups even at the highest hydration level. We observed large water clusters that could span graphitic regions, oxidized regions and holes that have been experimentally observed in GO. Slow interlayer diffusion can be consistent with experimentally observed water transport in GO if holes lead to a shorter path length than previously assumed and sorption serves as a key rate-limiting step. PMID- 27388563 TI - The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx. AB - BACKGROUND: Invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. This poses substantial challenges to longitudinal study of paediatric airway microbiota. Non invasive upper airway sampling is an alternative method for monitoring airway microbiota; however, there are limited data describing the relationship of such results with lung microbiota in young children. In this study, we compared the upper and lower airway microbiota in young children to determine whether non invasive upper airway sampling procedures provide a reliable measure of either lung microbiota or clinically defined differences. RESULTS: The microbiota in oropharyngeal (OP) swabs, nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) from 78 children (median age 2.2 years) with and without lung disease were characterised using 16S rRNA gene sequencing. Permutational multivariate analysis of variance (PERMANOVA) detected significant differences between the microbiota in BAL and those in both OP swabs (p = 0.0001, Pseudo-F = 12.2, df = 1) and NP swabs (p = 0.0001; Pseudo-F = 21.9, df = 1) with the NP and BAL microbiota more different than the OP and BAL, as indicated by a higher Pseudo-F value. The microbiota in combined OP and NP data (upper airways) provided a more comprehensive representation of BAL microbiota, but significant differences between the upper airway and BAL microbiota remained, albeit with a considerably smaller Pseudo-F (PERMANOVA p = 0.0001; Pseudo-F = 4.9, df = 1). Despite this overall difference, paired BAL and upper airway (OP and NP) microbiota were >50 % similar among 69 % of children. Furthermore, canonical analysis of principal coordinates (CAP analysis) detected significant differences between the microbiota from clinically defined groups when analysing either BAL (eigenvalues >0.8; misclassification rate 26.5 %) or the combined OP and NP data (eigenvalues >0.8; misclassification rate 12.2 %). CONCLUSIONS: Upper airway sampling provided an imperfect, but reliable, representation of the BAL microbiota for most children in this study. We recommend inclusion of both OP and NP specimens when non-invasive upper airway sampling is needed to assess airway microbiota in young children who do not expectorate. The results of the CAP analysis suggest lower and upper airway microbiota profiles may differentiate children with chronic suppurative lung disease from those with persistent bacterial bronchitis; however, further research is needed to confirm this observation. PMID- 27388565 TI - Survival among clinical stage I-III rectal cancer patients treated with different preoperative treatments: A population-based comparison. AB - BACKGROUND: Radical resection is regarded as the cornerstone of rectal cancer treatment. Preoperative (chemo)radiotherapy and adjuvant chemotherapy are often administered. This population-based study compares the survival in clinical stage I-III rectal cancer patients who received either preoperative radiotherapy, preoperative chemoradiotherapy or no preoperative therapy. As secondary research questions, the association of type of radical resection and adjuvant chemotherapy on survival is also investigated. METHODS: Patients diagnosed between January 2006 and December 2011 with stage I-III rectal adenocarcinoma were retrieved from the Belgian Cancer Registry database. Multivariable Cox proportional hazards regression models were applied to evaluate the association of preoperative treatment, type of radical resection and use of adjuvant chemotherapy with survival, adjusting for the baseline characteristics age, gender, WHO performance status and clinical stage. RESULTS: A total of 5173 rectal cancer patients were identified. Preoperative treatment was as follows: none in 1354 (26.2%), radiotherapy in 797 (15.4%) and chemoradiotherapy in 3022 (58.4%) patients. The patient group who did not receive preoperative therapy or radiotherapy followed by radical resection had a lower observed survival compared to the patient group receiving preoperative chemoradiotherapy. The patient groups who underwent abdominoperineal excision and those receiving adjuvant chemotherapy had a worse observed survival compared to the patient group treated with sphincter-sparing surgery and no adjuvant therapy respectively. These effects were age-dependent. Multivariable analysis demonstrated similar findings for the observed survival conditional on surviving the first year since surgery. CONCLUSION: In this population-based study among clinical stage I-III rectal cancer patients treated with radical resection, a superior observed survival was noticed in the patient group receiving preoperative chemoradiotherapy compared to the patients groups receiving no or preoperative radiotherapy only, adjusting for case mix, type of radical resection and adjuvant chemotherapy. Additionally, higher adjusted observed survival was also detected for the patient groups with sphincter-sparing surgery or no adjuvant chemotherapy. PMID- 27388564 TI - The eicosanoids leukotriene D4 and prostaglandin E2 promote the tumorigenicity of colon cancer-initiating cells in a xenograft mouse model. AB - BACKGROUND: Colorectal cancer is one of the most common types of cancers worldwide. Recent studies have identified cancer-initiating cells (CICs) as a subgroup of replication-competent cells in the development of colorectal cancer. Although it is understood that an inflammation-rich tumor microenvironment presumably supports CIC functions, the contributory factors are not very well defined. The present study advances our understanding of the role of the eicosanoids leukotriene D4 (LTD4) and prostaglandin E2 (PGE2) in the tumorigenic ability of CICs and investigates the consequential changes occurring in the tumor environment that might support tumor growth. METHODS: In this study we used human HCT-116 colon cancer ALDH(+) cells in a nude mouse xenograft model. Protein expression and immune cell was determined in tumor-dispersed cells by flow cytometry and in tumor sections by immunohistochemistry. mRNA expressions were quantified using RT-q-PCR and plasma cytokine levels by Multiplex ELISA. RESULTS: We observed that LTD4 and PGE2 treatment augmented CIC-induced tumor growth. LTD4 and PGE2-treated xenograft tumors revealed a robust increase in ALDH and Dclk1 protein expression, coupled with activated beta-catenin signaling and COX-2 up regulation. Furthermore, LTD4 or PGE2 accentuated the accumulation of CD45 expressing cells within xenograft tumors. Further analysis revealed that these infiltrating immune cells consisted of neutrophils (LY6G) and M2 type macrophages (CD206(+)). In addition, LTD4 and PGE2 treatment significantly elevated the plasma levels of cysteinyl leukotrienes and PGE2, as well as levels of IL-1beta, IL-2, IL-6, TNF-alpha and CXCL1/KC/GRO. In addition, increased mRNA expression of IL-1beta, IL-6 and IL-10 were detected in tumors from mice that had been treated with LTD4 or PGE2. CONCLUSION: Our data suggest that both LTD4 and PGE2 promote CICs in initiating tumor growth by allowing modifications in the tumor environment. Our data indicate that new therapeutic strategies targeting eicosanoids, specifically LTD4 and PGE2, could be tested for better therapeutic management of colon cancer. PMID- 27388566 TI - Prospective, Randomized, Concurrently-Controlled Study of a Stent Graft versus Balloon Angioplasty for Treatment of Arteriovenous Access Graft Stenosis: 2-Year Results of the RENOVA Study. AB - PURPOSE: To present final, 2-year data from randomized comparison of an expanded polytetrafluoroethylene stent graft (SG) and percutaneous transluminal angioplasty (PTA) for treatment of arteriovenous graft (AVG) anastomotic stenoses. MATERIALS AND METHODS: A 28-site, prospective, controlled US study enrolled 270 patients with malfunctioning AVG anastomotic stenoses of >= 50%; 138 patients underwent SG placement, and 132 underwent PTA alone. Follow-up imaging and intervention were event-driven. RESULTS: The study was completed by 191 patients (97 SG, 94 PTA). Five patients were lost to follow-up or withdrew; 74 patients died during the study (38 SG, 36 PTA). At 12 months, treatment area primary patency (TAPP) was SG 47.6% versus PTA 24.8% (P < .001), access circuit primary patency (ACPP) was SG 24% versus PTA 11% (P = .007), and index of patency function (IPF) was SG 5.2 months/intervention +/- 4.1 versus PTA 4.4 months/intervention +/- 3.5 (P = .009). At 24 months, TAPP was SG 26.9% versus PTA 13.5% (P < .001), ACPP was SG 9.5% versus PTA 5.5% (P = .01), and IPF was SG 7.1 months/intervention +/- 7.0 versus PTA 5.3 months/intervention +/- 5.2; estimated number of reinterventions before graft abandonment was 3.4 for SG patients versus 4.3 for PTA patients. There were no significant differences in adverse events (P > .05) except for restenosis requiring reintervention rates of 82.6% in PTA patients versus 63.0% in SG patients (P < .001). CONCLUSIONS: At 2 years, SG use provided a sustained, greater than 2-fold advantage over PTA in treatment area and overall access patency. Time to subsequent intervention was longer in the SG group. PMID- 27388567 TI - High-Resolution Axonal Bundle (Fascicle) Assessment and Triple-Echo Steady-State T2 Mapping of the Median Nerve at 7 T: Preliminary Experience. AB - OBJECTIVES: The aims of this preliminary study were to determine the number of axonal bundles (fascicles) in the median nerve, using a high-resolution, proton density (PD)-turbo spin echo (TSE) fat suppression sequence, and to determine normative T2 values, measured by triple-echo steady state, of the median nerve in healthy volunteers and in patients with idiopathic carpal tunnel syndrome (CTS), at 7 T. MATERIALS AND METHODS: This prospective study was approved by the local ethics committee and conducted between March 2014 and January 2015. All study participants gave written informed consent. Six healthy volunteers (30 +/- 12 years) and 5 patients with CTS (44 +/- 16 years) were included. Measurements were performed on both wrists in all volunteers and on the affected wrist in patients (3 right, 2 left). Based on 5-point scales, 2 readers assessed image quality (1, very poor; 5, very good) and the presence of artifacts that might have a possible influence on fascicle determination (1, severe artifacts; 5, no artifacts) and counted the number of fascicles independently on the PD-TSE sequences. Furthermore, T2 values by region of interest analysis were assessed. Student t tests, a hierarchic linear model, and intraclass correlation coefficients (ICCs) were used for statistical analysis. RESULTS: Proton density-TSE image quality and artifacts revealed a median of 5 in healthy volunteers and 4 in patients with CTS for both readers. Fascicle count of the median nerve ranged from 13 to 23 in all subjects, with an ICC of 0.87 (95% confidence interval [CI], 0.67-0.95). T2 values were significantly higher (P = 0.023) in patients (24.27 +/- 0.97 milliseconds [95% CI, 22.19-26.38]) compared with healthy volunteers (21.01 +/- 0.65 milliseconds [95% CI, 19.61-22.41]). The ICC for all T2 values was 0.97 (95% CI, 0.96-0.98). CONCLUSIONS: This study shows the possibility of fascicle determination of the median nerve in healthy volunteers and patients with CTS (although probably less accurately) with high-resolution 7 T magnetic resonance imaging, as well as significantly higher T2 values in patients with CTS, which seems to be associated with pathophysiological nerve changes. PMID- 27388568 TI - Self-Poling of BiFeO3 Thick Films. AB - Bismuth ferrite (BiFeO3) is difficult to pole because of the combination of its high coercive field and high electrical conductivity. This problem is particularly pronounced in thick films. The poling, however, must be performed to achieve a large macroscopic piezoelectric response. This study presents evidence of a prominent and reproducible self-poling effect in few-tens-of-micrometer thick BiFeO3 films. Direct and converse piezoelectric measurements confirmed that the as-sintered BiFeO3 thick films yield d33 values of up to ~20 pC/N. It was observed that a significant self-poling effect only appears in cases when the films are heated and cooled through the ferroelectric-paraelectric phase transition (Curie temperature TC ~ 820 degrees C). These self-poled films exhibit a microstructure with randomly oriented columnar grains. The presence of a compressive strain gradient across the film thickness cooled from above the TC was experimentally confirmed and is suggested to be responsible for the self poling effect. Finally, the macroscopic d33 response of the self-poled BiFeO3 film was characterized as a function of the driving-field frequency and amplitude. PMID- 27388569 TI - Epidemiology of autism in adults across age groups and ability levels. AB - BACKGROUND: The epidemiology of autism in adults has relied on untested projections using childhood research. AIMS: To derive representative estimates of the prevalence of autism and key associations in adults of all ages and ability levels. METHOD: Comparable clinical diagnostic assessments of 7274 Adult Psychiatric Morbidity Survey participants combined with a population case register survey of 290 adults with intellectual disability. RESULTS: The combined prevalence of autism in adults of all ages in England was 11/1000 (95% CI 3 19/1000). It was higher in those with moderate to profound intellectual disability (odds ratio (OR) = 63.5, 95% CI 27.4-147.2). Male gender was a strong predictor of autism only in those with no or mild intellectual disability (adjusted OR = 8.5, 95% CI 2.0-34.9; interaction with gender, P = 0.03). CONCLUSIONS: Few adults with autism have intellectual disability; however, autism is more prevalent in this population. Autism measures may miss more women with autism. PMID- 27388570 TI - Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients. AB - BACKGROUND: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes. AIMS: We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes. METHOD: Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term. RESULTS: Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021). CONCLUSIONS: Only anti inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia. PMID- 27388571 TI - Mental health services, suicide and 7-day working. AB - BACKGROUND: Patients admitted to hospital at the weekend appear to be at increased risk of death compared with those admitted at other times. However, a 'weekend effect' has rarely been explored in mental health and there may also be other times of year when patients are vulnerable. AIMS: To investigate the timing of suicide in high-risk mental health patients. METHOD: We compared the incidence of suicide at the weekend v. during the week, and also in August (the month of junior doctor changeover) v. other months in in-patients, patients within 3 months of discharge and patients under the care of crisis resolution home treatment (CRHT) teams (2001-2013). RESULTS: The incidence of suicide was lower at the weekends for each group (incidence rate ratio (IRR) = 0.88 (95% CI 0.79 0.99) for in-patients, IRR = 0.85 (95% CI 0.78-0.92) for post-discharge patients, IRR = 0.87 (95% CI 0.78-0.97) for CRHT patients). Patients who died by suicide were also less likely to have been admitted at weekends than during the week (IRR = 0.52 (95% CI 0.45-0.60)). The incidence of suicide in August was not significantly different from other months. CONCLUSIONS: We found evidence of a weekend effect for suicide risk among high-risk mental health patients, but with a 12-15% lower incidence at weekends. Our study does not support the claim that safety is compromised at weekends, at least in mental health services. PMID- 27388572 TI - Increased mortality among people with anxiety disorders: total population study. AB - BACKGROUND: Anxiety disorders and depression are the most common mental disorders worldwide and have a striking impact on global disease burden. Although depression has consistently been found to increase mortality; the role of anxiety disorders in predicting mortality risk is unclear. AIMS: To assess mortality risk in people with anxiety disorders. METHOD: We used nationwide Danish register data to conduct a prospective cohort study with over 30 million person-years of follow up. RESULTS: In total, 1066 (2.1%) people with anxiety disorders died during an average follow-up of 9.7 years. The risk of death by natural and unnatural causes was significantly higher among individuals with anxiety disorders (natural mortality rate ratio (MRR) = 1.39, 95% CI 1.28-1.51; unnatural MRR = 2.46, 95% CI 2.20-2.73) compared with the general population. Of those who died from unnatural causes, 16.5% had comorbid diagnoses of depression (MRR = 11.72, 95% CI 10.11 13.51). CONCLUSIONS: Anxiety disorders significantly increased mortality risk. Comorbidity of anxiety disorders and depression played an important part in the increased mortality. PMID- 27388573 TI - Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. AB - BACKGROUND: Although clozapine is the 'gold standard' for treatment-refractory schizophrenia, meta-analyses of clozapine for this condition are lacking. AIMS: We conducted a systematic review and meta-analysis of clozapine treatment for people with treatment-refractory schizophrenia. METHOD: We searched the Cochrane Schizophrenia Group's trial register, PubMed and EMBASE and hand-searched key papers for randomised controlled trials of clozapine for treatment-refractory schizophrenia. RESULTS: Twenty-one papers with 25 comparisons were included. The number needed to treat was 9. Clozapine was superior for positive symptoms in both the short and long term. In the short term only clozapine was superior for total and negative symptoms, with higher response rates. Both funding source and dosage affected results. Higher baseline psychosis scores predicted better outcomes for clozapine in a meta-regression. CONCLUSIONS: Clozapine is superior for treatment-refractory disorder but if there is no response by 6 months medications with lower adverse reactions should be considered. PMID- 27388574 TI - Use of lithium and cancer risk in patients with bipolar disorder: population based cohort study. AB - BACKGROUND: Lithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer. AIMS: To investigate the association between lithium and cancer risk in patients with bipolar disorder. METHOD: A retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer. RESULTS: Compared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554-0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516-1.125), 0.919 (95% CI 0.640-1.318) and 0.552 (95% CI 0.367-0.831), respectively. CONCLUSIONS: Lithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose-response relationship for cancer risk reduction was observed. PMID- 27388575 TI - Plasmid-mediated colistin-resistant Escherichia coli detected from 2014 in Norway. PMID- 27388576 TI - Contradicting interplay between insulin-like growth factor-1 and miR-486-5p in primary NK cells and hepatoma cell lines with a contemporary inhibitory impact on HCC tumor progression. AB - In this study, an impaired natural killer (NK) cell cytolytic activity in 135 hepatocellular carcinoma (HCC) patients parallel to a reduced expression level of insulin-like growth factor (IGF)-1 in NK cells of HCC patients has been revealed. Ectopic expression of miR-486-5p, a direct upstream regulator of IGF-1, restored the endogenous level of IGF-1 in NK cells of HCC patients, thus augmenting its cytolytic activity against Huh7 cells in an opposite manner to the IGF-1 siRNAs. Unorthodoxly, over-expression of miR-486-5p in target hepatocytes resulted in the repression of IGF-1, suppression of Huh7 cells proliferation and viability in a similar pattern to the IGF-1 siRNAs. Therefore, this study highlights a potential role of IGF-1 in modulating cytolytic potential of NK cells of HCC patients. miR 486-5p acts in a cell-specific manner, differentially modulating IGF-1 expression in NK cells and their target hepatocytes with a contemporary inhibitory impact on HCC progression. PMID- 27388577 TI - Activity levels after reverse shoulder arthroplasty. AB - BACKGROUND: Aim of this study was to analyze whether patients undergoing reverse shoulder arthroplasty (RSA) surgery are able to successfully return to sports and afterwards. METHODS: Thirty-eight patients treated with RSA for Cuff Tear Arthropathy (CTA) were included. Two sub-groups were built: Patients who have participated in sports activities within the last 5 years prior surgery [Group A: n = 21 (55 %)] and patients who have never participated in sports [Group B: n = 17 (45 %)]. Evaluation was based on a questionnaire asking types of sports, frequency, and time to return to sports. RESULTS: Mean age in Group A at the time of surgery was 76.2 (65-85) years and 78.4 (68-92) years in Group B. Most patients were women [n = 35 (92 %)]. Mean follow-up was 4.8 years (2.4-9.4) years. Fifteen (71 %) patients in Group A participated in sports at the time prior to surgery. Fourteen (67 %) patients returned to sports after surgery. The returning rate was 93 %. Six (29 %) patients of Group A stated that one reason they underwent shoulder replacement surgery was to continue to participate in sports. All active patients performed swimming at final follow up. CONCLUSIONS: Most patients being active prior to reverse shoulder arthroplasty surgery are successfully able to return to their activity afterwards. PMID- 27388578 TI - Biological and proteomic characterization of a composite mesh for abdominal wall hernia treatment: Reference Study. AB - AIMS: The industrial development of a product requires performing a deep analysis to highlight its characteristics useful for future design. The clinical use of a product stimulates knowledge improvement about it in a constant effort of progress. This work shows the biological characterization of CMC composite mesh. CMC polypropylene prosthesis was seeded with Human fibroblast BJ. Samples (cells and medium) were collected at different time points in order to perform different analysis: inflammatory markers quantification; collagens immunohistochemistry; matrix metalloproteinases zimography; extracellular matrix proteomic profile. FINDINGS: CMC presented a good cell viability rate and cell growth during the 21 days. The inflammatory profile showed an initial secretion of anti-inflammatory IL-10 and a final increase of pro-inflammatory IL-6. Immunocytochemistry highlighted a similar Collagen type I/type III ratio. The proteomic analysis evidenced the ECM protein content profile composed, mainly, by collagens, fibronectin, laminin. MMPs resulted both expressed when in contact to mesh. CONCLUSIONS: CMC shows a good cell biocompatibility and growth. The increase of pro-inflammatory markers could stimulate proliferation, influencing the integration process in human body. Proteomics highlights the ECM modulation by CMC. An integrated investigation of these biological analyses with mechanical data should improve the design process of a new product. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2045-2052, 2017. PMID- 27388579 TI - Linear, non-linear and plastic bending deformation of cellulose nanocrystals. AB - The deformation behaviour of cellulose nanocrystals under bending loads was investigated by using atomistic molecular dynamics (MD) simulations and finite element analysis (FEA), and compared with electron micrographs of ultrasonicated microfibrils. The linear elastic, non-linear elastic, and plastic deformation regions were observed with increasing bending displacements. In the linear elastic region, the deformation behaviour was highly anisotropic with respect to the bending direction. This was due to the difference in shear modulus, and the deformation could be approximated by standard continuum mechanics using the corresponding elastic tensors. Above the linear elastic region, the shear deformation became a dominant factor as the amplitude of shear strain drastically increased. Plastic deformation limit was observed at the bending angle above about 60 degrees , independent of the bending direction. The morphology of the atomistic model of plastically deformed cellulose crystals showed a considerable similarity to the kinked cellulose microfibrils observed by transmission electron microscopy. Our observations highlight the importance of shear during deformation of cellulose crystals and provide an understanding of basic deformations occurring during the processing of cellulose materials. PMID- 27388580 TI - Single crossclamp: Safe training tool for coronary artery bypass grafting. AB - OBJECTIVE: The single-crossclamp technique for coronary artery bypass grafting is recognized to reduce manipulation of the ascending aorta, and thereby improve neurological outcomes. However, there is a perceived disadvantage of long cardiopulmonary bypass and crossclamp times. Our objective was to evaluate outcomes with this technique and determine whether it is safe for training. METHODS: Patients undergoing coronary artery bypass between October 2005 and February 2014 with use of the single-crossclamp method were divided into 2 groups: a consultant group (n = 1024), and a trainee group (n = 504), depending on the primary surgeon. Their outcomes were compared. RESULTS: The consultants operated on more nonelective patients who had a higher risk profile (mean additive EuroSCORE I 4.05 vs. 3.80, p = 0.085; logistic EuroSCORE I 4.36 vs. 3.64, p = 0.002). There were 9 (0.9%) deaths in the consultant group and 5 (1%) in the trainee group. The mean number of grafts in the consultant group was greater, but the crossclamp time was similar and cardiopulmonary bypass time was shorter. There were 4 (0.4%) cerebrovascular events in the consultant group and 3 (0.6%) in the trainee group. Postoperative stay was shorter in the trainee group (7.19 vs. 7.97 days, p = 0.033). Other complication rates were similar. CONCLUSIONS: The technique has excellent outcomes, especially neurological, and is safe for training junior surgeons. PMID- 27388581 TI - Synthesis of 1,2-Benzothiazines by a Rhodium-Catalyzed Domino C-H Activation/Cyclization/Elimination Process from S-Aryl Sulfoximines and Pyridotriazoles. AB - A method for the synthesis of a large number of 1,2-benzothiazines bearing pyridyl as well as carbonyl groups is developed from rhodium-catalyzed carbene insertions into aromatic C-H bonds of S-aryl sulfoximines using pyridotriazoles by denitrogenative cyclization followed by the elimination of alcohols. The present method involves the N-H/C-H activation of simple alkyl aryl sulfoximines and has the advantages of a broad substrate scope, high functional group tolerance, and good regioselectivity. PMID- 27388582 TI - Unraveling Triplet Excitons Photophysics in Hyper-Cross-Linked Polymeric Nanoparticles: Toward the Next Generation of Solid-State Upconverting Materials. AB - The technological application of sensitized upconversion based on triplet-triplet annihilation (TTA) requires the transition from systems operating in liquid solutions to solid-state materials. Here, we demonstrate that the high upconversion efficiency reported in hyper-cross-linked nanoparticles does not originate from residual mobility of the embedded dyes as it happens in soft hosts. The hyper-reticulation from one side blocks the dyes in fixed positions, but on the other one, it suppresses the nonradiative spontaneous decay of the triplet excitons, reducing intramolecular relaxations. TTA is thus enabled by an unprecedented extension of the triplet lifetime, which grants long excitons diffusion lengths by hopping among the dye framework and gives rise to high upconversion yield without any molecular displacement. This finding paves the way for the design of a new class of upconverting materials, which in principle can operate at excitation intensities even lower than those requested in liquid or in rubber hosts. PMID- 27388583 TI - An Exploratory Association Study of Alcohol Use Disorder and DNA Methylation. AB - BACKGROUND: Epigenetic factors, including DNA methylation, play an important role in the etiology of alcohol use disorders (AUDs). Noncandidate-based methylome wide studies leveraging multiple tissue types are needed in order to identify a set of CpG targets that reliably differentiate AUD patients from controls and strongly correlate across brain tissue and more commonly collected tissue types (e.g., buccal cells). METHODS: Postmortem precuneus brain tissue samples were collected from 49 alcohol-dependent (AD) cases and 47 controls (sample I), and DNA was extracted from precuneus and putamen brain tissue and buccal cells in 24 postmortem subjects (sample II). Methylation levels were analyzed at over 450,000 CpG sites in both samples. CpGs that demonstrated significant methylation differences between cases and controls were advanced for further analysis with the goal of identifying CpGs that also demonstrated consistent methylation correlations across tissue type. RESULTS: In the primary analysis, 244 hypomethylated and 188 hypermethylated CpGs met a priori criteria for both significant methylation differences between cases and controls as well as significant correlation across brain and buccal cell tissue types, employing stringent Bonferroni p-value correction. Many of these CpGs were involved in gene networks related to lipid metabolism, immune response, inflammatory response/disease, and gastro-intestinal disease. CONCLUSIONS: More than 400 CpGs demonstrated differences in methylation between AD cases and controls and showed significant correlation across tissue types. Several genes and pathways (e.g., inflammation and immune functioning) that have been previously associated with AUD were identified in the current analyses. PMID- 27388584 TI - Notes from The Field: Ebola Virus Disease Cluster - Northern Sierra Leone, January 2016. AB - On January 14, 2016, the Sierra Leone Ministry of Health and Sanitation was notified that a buccal swab collected on January 12 from a deceased female aged 22 years (patient A) in Tonkolili District had tested positive for Ebola virus by reverse transcription-polymerase chain reaction (RT-PCR). The most recent case of Ebola virus disease (Ebola) in Sierra Leone had been reported 4 months earlier on September 13, 2015 (1), and the World Health Organization had declared the end of Ebola virus transmission in Sierra Leone on November 7, 2015 (2). The Government of Sierra Leone launched a response to prevent further transmission of Ebola virus by identifying contacts of the decedent and monitoring them for Ebola signs and symptoms, ensuring timely treatment for anyone with Ebola, and conducting an epidemiologic investigation to identify the source of infection. PMID- 27388585 TI - Landscape of Phosphatidylinositol-3-Kinase Pathway Alterations Across 19 784 Diverse Solid Tumors. AB - Importance: Molecular aberrations in the phosphatidylinositol-3-kinase (PI3K) pathway drive tumorigenesis. Frequently co-occurring alterations in hormone receptors and/or human epidermal growth factor receptor 2 (HER2) may be relevant to mechanisms of response and resistance. Objective: To identify patterns of aberration in the PI3K and interactive pathways that might lead to targeted therapy opportunities in clinical practice. Design, Setting, and Participants: From January 2013 through December 2014, 19 784 consecutive tumor samples (>40 cancer types) were sent from thousands of clinicians in 60 countries to a single commercial laboratory for molecular profiling, including next generation sequencing, protein expression (immunohistochemical analysis [IHC]), and gene amplification (fluorescent in situ hybridization or chromogenic in situ hybridization). Main Outcomes and Measures: Patterns in targetable genomic and proteomic alterations in the PI3K pathway and coincidence with hormone receptor and HER2 alterations. Exposures: Molecular profiling across solid tumors. Results: Overall, 38% of patients had an alteration in 1 or more PI3K pathway components, most commonly phosphatase and tensin homologue (PTEN) loss (by IHC) (30% of all patients), followed by mutations in PIK3CA (13%), PTEN (6%), or AKT1 (1%). Seventy percent of patients with endometrial cancer and more than 50% of patients with breast, prostate, anal, hepatocellular, colorectal, and cervical cancer exhibited alterations in at least 1 PI3K pathway gene and/or gene product. Examples of frequent aberrations included PTEN loss in hepatocellular (57% of patients), colorectal (48%), gastric (36%), prostate (52%), and endometrial cancer (49%); PIK3CA mutations in endometrial (37%), breast (31%), cervical (29%), and anal cancer (27%). PIK3CA, PTEN, and AKT1 mutations occurred more frequently in the presence of hormone receptor overexpression (androgen, progesterone, or estrogen receptor). PIK3CA mutations were also more common in the HER2-positive than in the HER2-negative group; the opposite pattern was seen for PTEN mutation or PTEN loss. Conclusions and Relevance: PI3K pathway aberrations are among the most common in cancer. They do not segregate by classic cancer histologic characteristics. Patterns of biomarker coalterations involving HER2 and hormone receptors may be important for optimizing combination treatments across cancer types. PMID- 27388586 TI - Intravenous Thrombolysis Increases the Rate of Dramatic Recovery in Patients with Acute Stroke with an Unknown Onset Time and Negative FLAIR MRI. AB - BACKGROUND AND PURPOSE: The safety and feasibility of intravenous thrombolysis using recombinant tissue plasminogen activator (IV-tPA) were retrospectively compared between patients with unknown onset time and no ischemia on fluid attenuated inversion recovery (negative FLAIR) and patients receiving standard therapy. METHODS: Acute stroke patients with unknown onset times were treated using IV-tPA if they had: negative FLAIR; internal carotid artery and/or middle cerebral artery occlusion; and a diffusion-weighted imaging (DWI)-Alberta Stroke Programme Early CT Score >=5. All patients had abnormal DWI scans indicating an acute stroke. IV-tPA therapy was performed within 3-4.5 h of first found abnormal time (FAT). Patients who were admitted within 3-4.5 h of FAT and did not receive IV-tPA therapy despite the same imaging findings were extracted from our registry as controls. RESULTS: There were 24 patients in the IV-tPA group and 28 in the control group. None of the IV-tPA group and 1 (4%) of the control group patients experienced symptomatic intracerebral hemorrhage (P = 1.000). The rate of dramatic recovery at day 7 (>=10-point reduction in the total National Institutes of Health Stroke Scale [NIHSS] score or NIHSS score of 0-1) was 46% in the IV-tPA group and 18% in the control group (P = .038). Multivariate regression analysis revealed that IV-tPA was an independent predictor of dramatic recovery at day 7 (odds ratio 13.74; 95% confidence interval, 1.95-96.92; P = .009). CONCLUSIONS: IV-tPA may safely increase the rate of dramatic recovery in acute stroke patients with unknown onset times and negative FLAIR. PMID- 27388587 TI - High-Resolution Group Quantization Phase Processing Method in Radio Frequency Measurement Range. AB - Aiming at the more complex frequency translation, the longer response time and the limited measurement precision in the traditional phase processing, a high resolution phase processing method by group quantization higher than 100 fs level is proposed in radio frequency measurement range. First, the phase quantization is used as a step value to quantize every phase difference in a group by using the fixed phase relationships between different frequencies signals. The group quantization is formed by the results of the quantized phase difference. In the light of frequency drift mainly caused by phase noise of measurement device, a regular phase shift of the group quantization is produced, which results in the phase coincidence of two comparing signals which obtain high-resolution measurement. Second, in order to achieve the best coincidences pulse, a subtle delay is initiatively used to reduce the width of the coincidences fuzzy area according to the transmission characteristics of the coincidences in the specific medium. Third, a series of feature coincidences pulses of fuzzy area can be captured by logic gate to achieve the best phase coincidences information for the improvement of the measurement precision. The method provides a novel way to precise time and frequency measurement. PMID- 27388588 TI - Hydrogen-Bond and Supramolecular-Contact Mediated Fluorescence Enhancement of Electrochromic Azomethines. AB - An electronic push-pull fluorophore consisting of an intrinsically fluorescent central fluorene capped with two diaminophenyl groups was prepared. An aminothiophene was conjugated to the two flanking diphenylamines through a fluorescent quenching azomethine bond. X-ray crystallographic analysis confirmed that the fluorophore formed multiple intermolecular supramolecular bonds. It formed two hydrogen bonds involving a terminal amine, resulting in an antiparallel supramolecular dimer. Hydrogen bonding was also confirmed by FTIR and NMR spectroscopic analyses, and further validated theoretically by DFT calculations. Intrinsic fluorescence quenching modes could be reduced by intermolecular supramolecular contacts. These contacts could be engaged at high concentrations and in thin films, resulting in fluorescence enhancement. The fluorescence of the fluorophore could also be restored to an intensity similar to its azomethine-free counterpart with the addition of water in >50 % v/v in tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), and acetonitrile. The fluorophore also exhibited reversible oxidation and its color could be switched between yellow and blue when oxidized. Reversible electrochemically mediated fluorescence turn-off on turn-on was also possible. PMID- 27388589 TI - Comparative study between the effects of replacement therapy with liquid and tablet formulations of levothyroxine on mood states, self-perceived psychological well-being and thyroid hormone profile in recently thyroidectomized patients. AB - Following thyroid surgery, levothyroxine therapy is used to replace deficient thyroid hormones and prevent postoperative thyroid hypofunction. We compared the effects of replacement therapy with either liquid or tablet formulation of levothyroxine on mood states, self-perceived mental well-being and thyroid hormone profile in recently thyroidectomized patients. Profile of mood states, General Heath Questionnaire 12-items and thyroid hormone profile were assessed in recently (5-7 days) thyroidectomized patients at baseline and 2 months after randomization to replacement therapy with either liquid (n = 77) or tablet (n = 78) formulation of levothyroxine. After 2 months under levothyroxine replacement treatment, significant improvements of Positive Affect Scale (p < 0.001) and Negative Affect Scale (p < 0.001) of Profile of mood states, as well as of General Heath Questionnaire 12-items (p < 0.001) were observed in the study population. However, there were greater variations observed in patients assigned to liquid levothyroxine formulation in comparison to those who were assigned to levothyroxine in the form of tablet (time * treatment interaction: Positive Affect Scale of Profile of mood states, p = 0.030; Negative Affect Scale of Profile of mood states, p < 0.0001; General Heath Questionnaire 12-items, p = 0.003). As expected, circulating TSH levels significantly decreased (p <0.001) while FT3 and FT4 levels significantly increased (p < 0.0001 for both) under levothyroxine replacement therapy. These changes were significantly greater in patients treated with liquid levothyroxine formulation (time * treatment interaction: TSH, p = 0.011; FT3, p = 0.016; FT4, p = 0.028). Our data indicate a greater efficacy of liquid formulation of levothyroxine in ameliorating mood states and self-perception of mental well-being and thyroid hormone profile after 2 months of replacement therapy in recently thyroidectomized patients. PMID- 27388590 TI - Fetuin-A, adiposity-linked insulin resistance and responsiveness to an educational-based weight excess reduction program: a population-based survey in prepubertal schoolchildren. AB - The secreted hepatokine fetuin-A emerges as an independent predictor of type 2 diabetes in adulthood. The overall aims of this study were: (1) to investigate the associations of fetuin-A with adiposity and insulin resistance, as well as its relationship with adipokines, in prepubertal children, and, (2) to evaluate whether, in prepubertal obesity, serum fetuin-A levels may either change or predict the responsiveness to an educational-based weight excess reduction program. We studied 200 prepubertal children (boys/girls: 89/111; Tanner stage 1; age: 5-13 years), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 100 individuals were lean (boys/girls: 57/43) and 100 obese (boys/girls: 54/46). A subset of 53 obese individuals (boys/girls: 28/25; age: 6-12 years) were also evaluated after a weight excess reduction program. Serum fetuin-A, leptin, total and high molecular weight adiponectin levels, as well as homeostasis model assessment of insulin resistance were assessed. When compared with lean, obese children exhibited higher ( p < 0.0001) fetuin-A concentrations, without differences between sex. Fetuin-A was positively associated with adiposity, homeostasis model assessment of insulin resistance, and leptin levels. In multivariate analysis, the associations between fetuin-A and leptin or homeostasis model assessment of insulin resistance lost the significance after adjustment for BMI Z-score, which, in turn, represented an independent determinant of fetuin-A (R 2adj 0.327; p < 0.0001). Notably, after weight excess reduction program, fetuin-A levels dropped ( p < 0.0001 vs. basal). Interestingly, no significant differences of fetuin-A concentrations between responders and no responders were found. In prepubertal children, fetuin-A represents an early marker of adiposity, and its reduction after lifestyle intervention may partly contribute to the beneficial effects of weight excess reduction program. PMID- 27388591 TI - Hyperglycemia in pasireotide-treated patients with acromegaly and its treatment. PMID- 27388592 TI - Effect of operational and design parameters on performance of pilot-scale horizontal subsurface flow constructed wetlands treating university campus wastewater. AB - Three horizontal subsurface flow (HSF) pilot-scale constructed wetland (CW) units operated for 3 years treating municipal wastewater originating from a university campus. The main objective of the study was the evaluation of the performance of these systems under several operational, design, and climatic conditions. Several parameters and factors were investigated, including the influence of temperature, vegetation, and hydraulic residence time. The results were compared to those of a previous study conducted in the same pilot-scale units and under the same operational conditions where synthetic municipal wastewater was used. Results show the satisfying overall performance of the CW units. Performance seems to be influenced by vegetation, temperature, and hydraulic residence time (HRT). The planted units produced better results than the unplanted one while, generally, all units operated better under warmer conditions. In addition, longer HRTs contributed to higher removal efficiencies. Finally, the systems showed higher removal efficiencies in the previous study (synthetic wastewater) regarding organic matter removal, while for the other pollutants, the present study (real wastewater) showed higher or comparable performance in most cases and especially in the planted units. The study also shows the overall good, continuous, and long term operation of CW systems, since these systems operate for about 13 years. PMID- 27388593 TI - Treatment of a simulated textile wastewater containing the Reactive Orange 16 azo dye by a combination of ozonation and moving-bed biofilm reactor: evaluating the performance, toxicity, and oxidation by-products. AB - In this study, an aqueous solution containing the azo dye Reactive Orange 16 (RO16) was subjected to two sequential treatment processes, namely: ozonation and biological treatment in a moving-bed biofilm reactor (MBBR). The most appropriate ozonation pretreatment conditions for the biological process and the toxicity of the by-products resulting from RO16 ozone oxidation were evaluated. The results showed that more than 97 % of color removal from the dye solutions with RO16 concentrations ranging from 25 to 100 mg/L was observed in 5 min of ozone exposure. However, the maximum total organic carbon removal achieved by ozonation was only 48 %, indicating partial mineralization of the dye. Eleven intermediate organic compounds resulting from ozone treatment of RO16 solution were identified by LC/MS analyses at different contact times. The toxicity of the dye-containing solution decreased after 2 min of ozonation, but increased at longer contact times. The results further demonstrated that the ozonolysis products did not affect the performance of the subsequent MBBR, which achieved an average chemical oxygen demand (COD) and ammonium removal of 93 +/- 1 and 97 +/- 2 %, respectively. A second MBBR system fed with non-ozonated dye-containing wastewater was run in parallel for comparison purposes. This reactor also showed an appreciable COD (90 +/- 1 %) and ammonium removal (97 +/- 2 %), but was not effective in removing color, which remained practically invariable over the system. The use of short ozonation times (5 min) and a compact MBBR has shown to be effective for the treatment of the simulated textile wastewater containing the RO16 azo dye. PMID- 27388594 TI - Evaluation of rhamnolipid addition on the natural attenuation of estuarine sediments contaminated with diesel oil. AB - The aim of the present study was to assess the bioremediation of estuarine sediments contaminated with diesel oil. The following two experiments were performed: natural attenuation (NA) and stimulated natural attenuation (SNA), using rhamnolipid as biosurfactant. Sediment samples were accommodated into glass columns and then contaminated with diesel oil on the top. The column profiles were separated into surface, middle, and bottom for the analyses. The 16 polycyclic aromatic hydrocarbons (PAHs) prioritized by US Environmental Protection Agency (EPA) were monitored for 349 days. Those with three and four rings showed increasing concentrations through the operation period in the middle and bottom samples, particularly between days 111 and 338, and in the SNA experiment. Those with five and six rings were also detected in the deeper portions of the columns, suggesting the percolation of PAHs with a high molecular weight. Total organic carbon was reduced by 91 and 89 % in the NA and SNA samples, respectively, although no statistically significant differences (p > 0.05) were found between the two treatments. The analyses by denaturing gradient gel electrophoresis indicated a slight shift in the microbial community structure over the experiments. Microorganisms belonging to the gamma-Proteobacteria phylum were the main bacteria involved. The archaeal community exhibited dominance of hydrogenotrophic methanogens, indicating the obligate anaerobic biodegradation of intermediate compounds from hydrocarbon degradation. PMID- 27388595 TI - Photochemical behavior of carbon nanotubes in natural waters: reactive oxygen species production and effects on *OH generation by Suwannee River fulvic acid, nitrate, and Fe (III). AB - The photochemical activities of three kinds of carbon nanotubes (CNTs) were investigated in the present study. Efficient procedures of dispersing the three kinds of carbon nanotubes in water were established, and the quantitative analysis methods were also developed by TOC-absorbance method. High pH value or low ionic strength of the colloidal solutions facilitated the dispersion of CNTs. The suspensions of three kinds of CNTs could generate singlet oxygen ((1)O2) and hydroxyl radical (*OH) under irradiation of simulated sunlight, while superoxide radical (O2 (*-)) was not detected. The steady-state concentrations of (1)O2 and *OH generated by these CNTs were also determined. The presence of CNTs in natural waters can affect the photochemical behavior of water constituents, such as nitrate, dissolved organic matter, and Fe(3+). Specifically, in nitrate solution, the presence of CNTs could inhibit the generation of *OH by nitrate through light screening effect, while the quenching effect of hydroxyl radicals by CNTs was not observed. Besides light screening effect, the three kinds of CNTs used in the experiments also have a strong inhibiting effect on the ability of DOM to produce *OH by binding to the active sites. Moreover, the adsorption of Fe(3+) on MWCNT OH and MWCNT-COOH could lead to its inactivation of formation of *OH in acidic conditions. However, the presence of the three kinds of CNTs did not affect the ligand-to-metal charge transfer (LMCT) reaction of DOM-Fe (III) complex. PMID- 27388596 TI - Antibacterial and antifouling activities of chitosan/TiO2/Ag NPs nanocomposite films against packaged drinking water bacterial isolates. AB - TiO2 and Ag NPs are widely used as antibacterial agents against many bacterial pathogens. Chitosan (polymer) itself acts as a strong antibacterial agent. Hence, chitosan/TiO2/Ag NPs incorporated nanocomposite film was prepared against packed drinking water bacterial strains. A concentration-dependent increase in the reduction of cell viability was observed in all the isolates under UV-C and dark exposure conditions. The bacteria consortium showed greater resistance against antibacterial effects of chitosan/TiO2/Ag nanocomposite as compared to single isolates. Glycocalyx test and mass assessment conclude the effective antibacterial activity by inhibiting bacterial adhesion on the film surface. The release of LDH and generation of ROS act as the predominant antibacterial mechanism induced by TiO2/Ag NPs. Surface characterization of chitosan/TiO2/Ag nanocomposite was studied by FTIR and XRD analyses and SEM analysis after interaction with the bacteria. PMID- 27388597 TI - Fibre tract analysis using diffusion tensor imaging reveals aberrant connectivity in a rat model of depression. AB - OBJECTIVES: Abnormal brain connectivity has been described in depressive disorder. However, these studies are correlational or cross-sectional and their design does not examine causal relationships. We aimed to investigate structural connectivity in a genetic rat model of depression. METHODS: Using diffusion tensor imaging (DTI), we reconstructed white matter tracts and analysed fractional anisotropy (FA) and diffusivity indices (mean, axial and radial) to investigate structural connectivity in fibre tracts implicated in major depression: the corpus callosum, fornix, cingulum and anterior commissures. RESULTS: Tractography-based analysis revealed that, compared to Wistar control rats, the Wistar-Kyoto strain (WKY) rat model of depression exhibited decreased connectivity, manifested by decreased FA in the corpus callosum, right and left anterior commissures. A statistical trend of decreased FA was observed in both the right and left cingulum. Increased diffusivity (mean diffusion) was detected in both the corpus callosum and the fornix of WKY rats compared to controls. Voxel-based analysis confirmed differences between WKY and controls in the regions investigated. CONCLUSIONS: Decreased connectivity in a genetic rat model of depression corroborates the findings in patients suffering from major depression suggesting that the vulnerability for developing depression is mainly polygenic and less likely to be due to childhood adversity per se. PMID- 27388598 TI - Protein partition coefficients can be estimated efficiently by hybrid shortcut calculations. AB - The extraction of therapeutic proteins like monoclonal antibodies in aqueous two phase systems (ATPS) is a suitable alternative to common cost intensive chromatographic purification steps within the downstream processing. Thereby the protein partitioning can be selectively changed using a displacement agent (additional salt) in order to allow for a successful purification of the target protein. Within this work a new shortcut strategy for the calculation of protein partition coefficients in polymer-salt ATPS is presented. The required protein solute (phase-forming component, displacement agent) interactions are covered by the cross virial coefficient B23 measured by composition gradient multi-angle light scattering (CG-MALS). Using this shortcut calculation allows for an efficient determination of the partition coefficients of the target protein immunoglobulin G (IgG) and the impurity human serum albumin (HSA) within PEG citrate and PEG-phosphate ATPS independently on the protein concentration. We demonstrate that the selection of a suitable displacement agent allowing for a selective purification of IgG from HSA is accessible by B23. Based on the determination of the protein-protein interactions via CG-MALS covered by the second osmotic virial coefficient B22 a further optimization of ATPS preventing protein precipitation is enabled. The results show that our approach contributes to an efficient downstream processing development. PMID- 27388599 TI - Evidence-based guidelines and consensus statements. PMID- 27388600 TI - Brief gatekeeper training for suicide prevention in an ethnic minority population: a controlled intervention. AB - BACKGROUND: Suicide is a critical public health problem around the globe. Asian populations are characterized by elevated suicide rates and a tendency to seek social support from family and friends over mental health professionals. Gatekeeper training programs have been developed to train frontline individuals in behaviors that assist at-risk individuals in obtaining mental health treatment. The purpose of this study is to assess the efficacy of a brief, multi component gatekeeper intervention in promoting suicide prevention in a high-risk Asian community in the United States. METHODS: We adapted an evidence-based gatekeeper training into a two-hour, multi-modal and interactive event for Japanese-Americans and related stakeholders. Then we evaluated the intervention compared to an attention control using mixed methods. RESULTS: A sample of 106 community members participated in the study. Intervention participants (n = 85) showed significant increases in all three types of intended gatekeeper behavior, all four measures of self-efficacy, and both measures of social norms relevant to suicide prevention, while the control group (n = 48) showed no significant improvements. Additional results showed significantly higher satisfaction and no adverse experiences associated with the gatekeeper training. The separate collection of qualitative data, and integration with the quantitative survey constructs confirmed and expanded understanding about the benefits of the intervention. CONCLUSIONS: A brief, multi-modal gatekeeper training is efficacious in promoting positive gatekeeper behaviors and self-efficacy for suicide prevention in an at-risk ethnic minority population of Japanese Americans. PMID- 27388602 TI - Scrotal hypoperfusion: a rare complication of umbilical artery catheterisation. PMID- 27388601 TI - Intracranial non-galenic pial arteriovenous fistula: A review of the literature. AB - An intracranial non-galenic pial arteriovenous fistula (NGPAVF) is a direct connection between the intracranial artery and vein without a nidus. NGPAVFs are clinically rare, and the current understanding of NGPAVFs is limited. This study searched PubMed for the currently available literature, and a review of the relevant publications revealed that NGPAVFs require aggressive treatment, spontaneous occlusion is uncommon, and the prognosis following conservative treatment is poor. NGPAVFs can be divided into congenital and traumatic (including iatrogenic) types. Clinically, NGPAVFs are characterized by congestive heart failure, epilepsy, hemorrhage, mass effects, and nerve function deficits. For the imaging examination of NGPAVFs, digital subtraction angiography (DSA) is still the gold standard for diagnosis, although magnetic resonance DSA (MRDSA) and 4D computed tomography angiography (CTA) can also provide hemodynamic data in a non-invasive manner. Current treatments for NGPAVFs include surgical resection and endovascular embolization, both of which can yield clinical improvements. However, potential postoperative complications should be addressed, such as fatal bleeding due to rupture and deep vein thrombosis. Some studies recommend postoperative anticoagulation to reduce postoperative thrombotic complications. PMID- 27388604 TI - Dare we think the unthinkable? PMID- 27388603 TI - Increasing incidence of thyroid cancer in the Nordic countries with main focus on Swedish data. AB - BACKGROUND: Radiofrequency radiation in the frequency range 30 kHz-300 GHz was evaluated to be Group 2B, i.e. 'possibly' carcinogenic to humans, by the International Agency for Research on Cancer (IARC) at WHO in May 2011. Among the evaluated devices were mobile and cordless phones, since they emit radiofrequency electromagnetic fields (RF-EMF). In addition to the brain, another organ, the thyroid gland, also receives high exposure. The incidence of thyroid cancer is increasing in many countries, especially the papillary type that is the most radiosensitive type. METHODS: We used the Swedish Cancer Register to study the incidence of thyroid cancer during 1970-2013 using joinpoint regression analysis. RESULTS: In women, the incidence increased statistically significantly during the whole study period; average annual percentage change (AAPC) +1.19 % (95 % confidence interval (CI) +0.56, +1.83 %). Two joinpoints were detected, 1979 and 2001, with a high increase of the incidence during the last period 2001-2013 with an annual percentage change (APC) of +5.34 % (95 % CI +3.93, +6.77 %). AAPC for all men during 1970-2013 was +0.77 % (95 % CI -0.03, +1.58 %). One joinpoint was detected in 2005 with a statistically significant increase in incidence during 2005-2013; APC +7.56 % (95 % CI +3.34, +11.96 %). Based on NORDCAN data, there was a statistically significant increase in the incidence of thyroid cancer in the Nordic countries during the same time period. In both women and men a joinpoint was detected in 2006. The incidence increased during 2006-2013 in women; APC +6.16 % (95 % CI +3.94, +8.42 %) and in men; APC +6.84 % (95 % CI +3.69, +10.08 %), thus showing similar results as the Swedish Cancer Register. Analyses based on data from the Cancer Register showed that the increasing trend in Sweden was mainly caused by thyroid cancer of the papillary type. CONCLUSIONS: We postulate that the whole increase cannot be attributed to better diagnostic procedures. Increasing exposure to ionizing radiation, e.g. medical computed tomography (CT) scans, and to RF-EMF (non-ionizing radiation) should be further studied. The design of our study does not permit conclusions regarding causality. PMID- 27388605 TI - Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention. AB - BACKGROUND: We previously reported the production of transgenic rats (APP21 line) that over-express human amyloid precursor protein (APP) containing Swedish and Indiana mutations. In order to generate a better model for Alzheimer's disease (AD), the APP21 rat line was used to generate double transgenic line that over expressed Presenilin 1 (PS1) with L166P mutation in addition to APP transgene (APP + PS1 line). RESULTS: Thirty-two double transgenic founders were generated and the ultimate transgenic founder was selected based on PS1 transgene copy number and level of amyloid-beta (Abeta)42 peptide. The APP + PS1 double transgenic rats had 38 times more PS1 in brains compared to APP rats. Behavioral assessment using Barnes maze showed that APP + PS1 rats exhibited a larger learning and memory deficit than APP21 rats. Double transgenic rats also produced more Abeta42. Histological examination of the brains showed that the APP21 rat line displayed neurofibrillary tangles and in contrast, the APP + PS1 line showed chromatolysis in hippocampal neurons and neuronal loss in CA3 region of hippocampus. CONCLUSIONS: Due to the separate segregation of APP and PS1 transgenes in APP + PS1 double transgenic rats, this transgenic line may be a valuable model for studying the effects of various levels of APP and PS1 transgenes on various aspects of brain pathologies associated with the AD phenotype. PMID- 27388606 TI - Structure and clinical correlates of obsessive-compulsive symptoms in a large sample of children and adolescents: a factor analytic study across five nations. AB - The underlying structure of obsessive-compulsive disorder (OCD) remains to be confirmed in child and adolescent populations. In this paper we report the first factor analytic study of individual OCD items from Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). OCD symptoms were assessed using the CY BOCS symptom checklist in a sample of 854 patients with OCD (7-18 years of age) recruited from clinics in five countries. Pooled data were subjected to exploratory and confirmatory factor analysis (CFA) to identify the optimal factor structure. Various models were tested for age and gender subgroups. Also, the invariance of the solution across age and gender was tested and associations with demographic and clinical factors were explored. A three-factor model provided the best-fit solution. It consisted of the following factors: (1) harm/sexual, (2) symmetry/hoarding, (3) contamination/cleaning. The factor structure was invariant for age and gender across subgroups. Factor one was significantly correlated with anxiety, and factor two with depression and anxiety. Factor three was negatively correlated with tic disorder and attention-deficit/hyperactivity disorder (ADHD). Females had higher scores on factor two than males. The OCD symptom structure in children and adolescents is consistent across age and gender and similar to results from recent child and adolescents although hoarding may not be a separate factor. Our three-factor structure is almost identical to that seen in early studies on adults. Common mental disorders had specific patterns of associations with the different factors. PMID- 27388607 TI - The size-distribution of Earth's lakes. AB - Globally, there are millions of small lakes, but a small number of large lakes. Most key ecosystem patterns and processes scale with lake size, thus this asymmetry between area and abundance is a fundamental constraint on broad-scale patterns in lake ecology. Nonetheless, descriptions of lake size-distributions are scarce and empirical distributions are rarely evaluated relative to theoretical predictions. Here we develop expectations for Earth's lake area distribution based on percolation theory and evaluate these expectations with data from a global lake census. Lake surface areas >=0.46 km(2) are power-law distributed with a tail exponent (tau = 2.14) and fractal dimension (d = 1.4), similar to theoretical expectations (tau = 2.05; d = 4/3). Lakes <0.46 km(2) are not power-law distributed. An independently developed regional lake census exhibits a similar transition and consistency with theoretical predictions. Small lakes deviate from the power-law distribution because smaller lakes are more susceptible to dynamical change and topographic behavior at sub-kilometer scales is not self-similar. Our results provide a robust characterization and theoretical explanation for the lake size-abundance relationship, and form a fundamental basis for understanding and predicting patterns in lake ecology at broad scales. PMID- 27388608 TI - Serum x03C9;-3 and x03C9;-6 Fatty Acids Are Not Associated with Personality Traits in Healthy Japanese Young People. AB - BACKGROUND: Recent studies have reported that polyunsaturated fatty acids (PUFAs) are associated with mood and behaviors including depression and suicide risk. The aim of this study was to examine the relationship between PUFAs and personality traits in healthy subjects. METHODS: A total of 279 subjects completed the Temperament and Character Inventory and Beck Depression Inventory. Serum levels of the PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), the x03C9; 6 fatty acid arachidonic acid (AA), and dihomo-x03B3;-linolenic acid were measured. RESULTS: Pearson's correlation analysis showed a positive correlation between DHA and cooperativeness scores. In the multiple regression analysis, harm avoidance scores were positively associated with AA, and a negative association was found between the EPA/AA ratio and reward dependence scores. However, these associations were nonsignificant after a Bonferroni correction. CONCLUSION: The results of the present study suggest that the blood levels of PUFAs are not likely to be associated with personality traits. PMID- 27388609 TI - Trajectories of health-related quality of life during the natural history of dementia: a six-wave longitudinal study. AB - OBJECTIVE: The objective of this study was to explore profiles of quality of life (QoL) trajectories during the natural history of dementia and individual variations contributing to QoL trajectories. METHODS: We conducted a longitudinal community-based study of 520 elderly people with mild cognitive impairment and 100 healthy people aged 60 years or over. We conducted six waves of assessment between October 2010 and May 2013 in Taiyuan, mainland China. Cognitively normal, mild cognitive impairment, global impairment, and Alzheimer's disease (AD) were defined as state 1, 2, 3, and 4, respectively. We assessed health-related QoL (HRQoL) via the Quality of Life-Alzheimer's Disease (QoL-AD) Chinese version. We used the latent growth curve model (LGCM) to investigate change in HRQoL over time. RESULTS: Latent growth curve model analysis revealed a mean initial QoL level of 29.865 with substantial variation and a significant mean slope for the whole sample. Multigroup LGCM showed substantial variations across individuals in initial QoL levels for each cognitive state transition group. For the slope factor, we found significant changes and variations for the transition from state 2 to 3 and from state 3 to 4. We estimated mean QoL levels over six assessments based on intercept, slope, and factor loadings for the whole sample and the three cognitive state transition groups. CONCLUSIONS: A decline in subjective QoL is not inevitable during the natural history of dementia in community settings, and there is a degree of individual variation in QoL. Future studies should investigate the factors associated with individual variations in QoL trajectories in AD. PMID- 27388611 TI - Welcome Two New Editors! PMID- 27388612 TI - Nursing Informatics Research and Emerging Trends in 2015. PMID- 27388613 TI - National Institutes of Health Appoints Patricia Flatley Brennan, RN, PhD, to Lead the National Library of Medicine. PMID- 27388614 TI - Use of Electronic Medication Administration Records to Reduce Perceived Stress and Risk of Medication Errors in Nursing Homes. PMID- 27388610 TI - Effect of obesity on the effectiveness of cardiac resynchronization to reduce the risk of first and recurrent ventricular tachyarrhythmia events. AB - BACKGROUND: Obesity is associated with multiple adverse cardiovascular conditions and may increase the risk of ventricular tachyarrhythmias (VT/VF). There is limited data on the association between obesity and risk of VT/VF requiring appropriate implantable cardioverter-defibrillator (ICD) therapies and the effectiveness of cardiac resynchronization therapy (CRT) to reduce risk for VT/VF. The multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) was design to investigate effectiveness of CRT therapy to reduce cardiovascular outcome for patients with heart failure (HF) and reduced ejection fraction. METHODS AND RESULTS: We identified patients enrolled in the MADIT CRT trial as obese (n = 433) and non-obese (n = 845) and analyzed their risk for appropriate device therapy for VT/VF, repeated VT/VF events, fast VT/VF, as well as events after first VT/VF episodes. Obesity was defined as body mass index (BMI) >=30 kg/m(2). Among ICD patients, the risk of first appropriate ICD therapy for VT/VF at 3 years was similar between obese and non-obese patients (23 vs. 21 %, p = 0.76). CRT-D treatment reduced the risk of first appropriate ICD therapy both in non-obese ([HR]; 0.58 [CI]: 0.42-0.79; p < 0.001) and obese patients (HR 0.75, 95 % CI 0.5-1.38; p = 0.179) (interaction p value 0.323). Similarly, a significant reduction in the risk of fast VT/VF was observed in non-obese patients ([HR]; 0.49 [CI]: 0.33-0.73; p < 0.001) and obese ([HR]; 0.49 [CI]: 0.29-0.81; p < 0.01), (interaction p value 0.984). CONCLUSION: Obese and non-obese patients with mild heart failure have a similar risk of ventricular tachyarrhythmias. Obesity in mild heart failure did not diminish the clinical benefit of cardiac resynchronization therapy to reduce risk for appropriate ICD therapy. Clinical trial registration http://clinicaltrials.gov/ct2/show/NCT00180271. PMID- 27388615 TI - Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy. AB - Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. DeltaUACR differed among treatment arms (placebo -24.6%, los -38.2%, spiro -51.6%, p=0.02). No correlation existed between DeltaUACR and DeltaTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (-20.9% vs +34.3%, p<0.01), V+I C(-18.8% vs +21.3%, p<0.01), and V+I-ApoB (-13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. TRIAL REGISTRATION NUMBER: NCT00381134; Results. PMID- 27388616 TI - Expression of 4-1BB and its ligand on blasts correlates with prognosis of patients with AML. AB - Costimulatory ligands (COLs) and their receptors (COR) regulate immune reactions and cellular survival and might be relevant in acute myeloid leukemia (AML). This study evaluated the clinical relevance of 4-1BBL, glucocorticoid-induced TNFR related protein (GITR) and ligand (GITRL), CD80, and CD86 in case of expression on AML blasts. 98 patients were evaluated at initial diagnosis. Immunophenotypically evaluated specific fluorescence index (SFI) levels of COR and COL on blasts were correlated with morphological, cytogenetic, and several prognostic parameters. Significantly higher COR expression was seen in monocytic versus non-monocytic AML subtypes; GITR, p=0.05; GITRL, p=0.005; CD86, p=0.001). Cut-off values for two COR and their ligands were evaluated: cases presenting with 4-1BB values above cut-off 1.2 SFI levels correlated (tendentially) significantly with a higher probability for disease-free survival (DFS, p=0.06) and a favorable HR of 0.2; p=0.04 for relapse. HR for death was also significantly lower in this group (0.12; p=0.04). In contrast, a lower probability for DFS and overall survival was seen in cases with 4-1BBL expression above 2.2 SFI levels (p=0.08 and p=0.09). In addition, multivariate analysis showed a significantly higher probability of death in this group (HR 10.3, p=0.04). Expression of CD80 and CD86 did not show significant prognostic relevance. On initial diagnosis, 4-1BB and 4-1BBL qualify as markers for prediction of patients' course and represent a valuable screening target for patients with AML at initial diagnosis. PMID- 27388617 TI - Pilot analysis of the Motivation Assessment for Team Readiness, Integration, and Collaboration (MATRICx) using Rasch analysis. AB - Healthcare services and the production of healthcare knowledge are increasingly dependent on highly functioning, multidisciplinary teams, requiring greater awareness of individuals' readiness to collaborate in translational science teams. Yet, there is no comprehensive tool of individual motivations and threats to collaboration that can guide preparation of individuals for work on well functioning teams. This prospective pilot study evaluated the preliminary psychometric properties of the Motivation Assessment for Team Readiness, Integration, and Collaboration (MATRICx). We examined 55 items of the MATRICx in a sample of 125 faculty, students and researchers, using contemporary psychometric methods (Rasch analysis). We found that the motivator and threat items formed separate constructs relative to collaboration readiness. Further, respondents who identified themselves as inexperienced at working on collaborative projects defined the motivation construct differently from experienced respondents. These results are consistent with differences in strategic alliances described in the literature-for example, inexperienced respondents reflected features of cooperation and coordination, such as concern with sharing information and compatibility of goals. In contrast, the more experienced respondents were concerned with issues that reflected a collective purpose, more typical of collaborative alliances. While these different types of alliances are usually described as representing varying aspects along a continuum, our findings suggest that collaboration might be better thought of as a qualitatively different state than cooperation or coordination. These results need to be replicated in larger samples, but the findings have implications for the development and design of educational interventions that aim to ready scientists and clinicians for greater interdisciplinary work. PMID- 27388618 TI - Transcutaneous Bilirubin Levels during the First Month of Life in Term and Late preterm Newborns. AB - OBJECTIVE: We aimed to develop a transcutaneous bilirubin (TcB) nomogram for assessment of the risk of significant hyperbilirubinemia and prolonged jaundice during the first month of life in term and late-preterm Turkish newborns. METHODS: On the basis of the daily (3rd, 7th, 15th and 30th days) TcB measurements, 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentiles, and 5 percentile tracks were obtained. TcB measurements were made by a transcutaneous bilirubinometer (JaundiceDetector JH20-1C). RESULTS: We screened 729 healthy term and late-preterm Turkish infants 3-30 days old and developed a nomogram of TcB levels. TcB level was >=5 mg/dl in 41.98% and 25.9% of infants at age 15.0 +/- 2.1 days and 30.9 +/- 2.6 days, respectively. The TcB measurement-based nomogram values of the 97th percentiles (cutoff values) at age 15.0 +/- 2.1 and 30.9 +/- 2.6 days were 11.4 (10.82-12.13) mg/dl and 10.0 (9.40-10.70) mg/dl, respectively. CONCLUSION: This nomogram can be used to determine the risk status of Turkish newborns regarding significant hyperbilirubinemia and prolonged jaundice on the basis of TcB measurement in the first month of life. PMID- 27388620 TI - The Minho Word Pool: Norms for imageability, concreteness, and subjective frequency for 3,800 Portuguese words. AB - Words are widely used as stimuli in cognitive research. Because of their complexity, using words requires strict control of their objective (lexical and sublexical) and subjective properties. In this work, we present the Minho Word Pool (MWP), a dataset that provides normative values of imageability, concreteness, and subjective frequency for 3,800 (European) Portuguese words three subjective measures that, in spite of being used extensively in research, have been scarce for Portuguese. Data were collected with 2,357 college students who were native speakers of European Portuguese. The participants rated 100 words drawn randomly from the full set for each of the three subjective indices, using a Web survey procedure (via a URL link). Analyses comparing the MWP ratings with those obtained for the same words from other national and international databases showed that the MWP norms are reliable and valid, thus providing researchers with a useful tool to support research in all neuroscientific areas using verbal stimuli. The MWP norms can be downloaded along with this article or from http://p pal.di.uminho.pt/about/databases . PMID- 27388619 TI - Retinal Vessel Analysis (RVA) in the Context of Subarachnoid Hemorrhage - A Proof of Concept Study. AB - BACKGROUND: Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH. METHODS: In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2-14) and eight patients at the time of follow-up (mean 4.6+/-1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling. RESULTS: Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2+/-4.3MU vs 110.9+/-11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7+/-17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion. CONCLUSION: RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort. PMID- 27388621 TI - The Nuclear DNA Content and Genetic Diversity of Lampetra morii. AB - We investigated the nuclear DNA content and genetic diversity of a river lamprey, the Korean lamprey Lampetra morii, which is distributed in the northeast of China. L. morii spends its whole life cycle in fresh water, and its adult size is relatively small (~160 mm long) compared with that of other lampreys. The haploid nuclear DNA content of L. morii is 1.618 pg (approximately 1.582 Gb) in germline cells, and there is ~15% germline DNA loss in somatic cells. These values are significantly smaller than those of Petromyzon marinus, a lamprey with a published draft genome. The chromosomes of L. morii are small and acrocentric, with a diploid modal number of 2n = 132, lower than some other lampreys. Sequence and AFLP analyses suggest that the allelic polymorphism rate (~0.14% based on examined nuclear and mitochondrial DNA sequences) of L. morii is much lower than that (~2%) of P. marinus. Phylogenetic analysis based on a mitochondrial DNA fragment confirms that L. morii belongs to the genus Lampetra, which, together with the genus Lethenteron, forms a sister group to P. marinus. These genetic background data are valuable for subsequent genetic and genomic research on L. morii. PMID- 27388622 TI - Classification model of amino acid sequences prone to aggregation of therapeutic proteins. AB - BACKGROUND: Total body clearance of biological drugs is for the most part dependent on the receptor mechanisms (receptor mediated clearance) and the concentration of antibodies aimed at administered drug - anti-drug-antibodies (ADA). One of the significant factors that induces the increase of ADA level after drug administration could be the aggregates present in the finished product or formed in the organism. Numerous attempts have been made to identify the sequence fragments that could be responsible for forming the aggregates - aggregate prone regions (APR). PURPOSE: The aim of this study was to find physiochemical parameters specific to APR that would differentiate APR from other sequences present in therapeutic proteins. METHODS: Two groups of amino acid sequences were used in the study. The first one was represented by the sequences separated from the therapeutic proteins (n = 84) able to form APR. A control set (CS) consisted of peptides that were chosen based on 22 tregitope sequences. RESULTS: Classification model and four classes (A, B, C, D) of sequences were finally presented. For model validation Cooper statistics was presented. CONCLUSIONS: The study proposes a classification model of APR. This consists in a distinction of APR from sequences that do not form aggregates based on the differences in the value of physicochemical parameters. Significant share of electrostatic parameters in relation to classification model was indicated. PMID- 27388624 TI - Correction: Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy. AB - [This corrects the article DOI: 10.1371/journal.pone.0144359.]. PMID- 27388623 TI - Influence of Ribavirin Serum Levels on Outcome of Antiviral Treatment and Anemia in Hepatitis C Virus Infection. AB - BACKGROUND: Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered. METHODS: The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1-4 infection, including 88 patients with available IL28b genotyping. RESULTS: Mean ribavirin levels varied between 0.68-5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia. CONCLUSION: While data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon. PMID- 27388625 TI - Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross sectional study. AB - BACKGROUND: Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva; (2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. METHODS: We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. RESULTS: The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p < 0.001), lower pH-values of their saliva (p < 0.001) and more bruxism symptoms (p < 0.001). However, we found no relevant trismus symptoms on comparing the two groups (p > 0.05). CONCLUSIONS: The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant decline of saliva buffer capacity in methamphetamine abusers may trigger the risk for dental erosions. Methamphetamine abusers and practitioners should be aware of these symptoms. PMID- 27388626 TI - Text Message Delivered Peer Network Counseling for Adolescent Smokers: A Randomized Controlled Trial. AB - Although adolescent tobacco use has declined in the last 10 years, African American high school seniors' past 30-day use has increased by 12 %, and as they age they are more likely to report lifetime use of tobacco. Very few urban youth are enrolled in evidenced-based smoking prevention and cessation programming. Therefore, we tested a text messaging smoking cessation intervention designed to engage urban youth through an automated texting program utilizing motivational interviewing-based peer network counseling. We recruited 200 adolescents (90.5 % African American) into a randomized controlled trial that delivered either the experimental intervention of 30 personalized motivational interviewing-based peer network counseling messages, or the attention control intervention, consisting of text messages covering general (non-smoking related) health habits. All adolescents were provided smart phones for the study and were assessed at baseline, and at 1, 3, and 6 months post intervention. Utilizing repeated measures general linear models we examined the effects of the intervention while controlling for race, gender, age, presence of a smoker in the home, and mental health counseling. At 6 months, participants in the experimental condition significantly decreased the number of days they smoked cigarettes and the number of cigarettes they smoked per day; they significantly increased their intentions not to smoke in the future; and significantly increased peer social support among girls. For boys, participants in the experimental condition significantly reduced the number of close friends in their networks who smoke daily compared to those in the control condition. Effect sizes ranged from small to large. These results provide encouraging evidence of the efficacy of text messaging interventions to reduce smoking among adolescents and our intervention holds promise as a large scale public health preventive intervention platform. PMID- 27388627 TI - The efficacy of intracolonic vancomycin for severe Clostridium difficile colitis: a case series. AB - BACKGROUND: Clostridium difficile infection (CDI) unresponsive to the standard treatments of metronidazole and oral vancomycin requires aggressive medical management and possible surgical intervention including colectomy. Intracolonic vancomycin therapy has been reported to be particularly promising in the setting of severe CDI in the presence of ileus. This is a descriptive case series exploring the effect of adjunctive intracolonic vancomycin therapy on the morbidity and mortality in patients with moderate to severe CDI. METHODS: A retrospective chart review was conducted on 696 patients with CDI seen at a single institution. Each patient was assigned a severity score and 127 patients with moderate to severe CDI were identified. We describe the clinical presentation, risk factors and hospital course comparing those that received adjunctive intracolonic vancomycin to those that only received standard therapy. RESULTS: The group that received adjunctive intracolonic vancomycin had higher rates of toxic megacolon, intensive care unit (ICU) admission, and colectomy, and yet maintained a similar mortality rate as the group that received only standard treatment. CONCLUSION: The intracolonic vancomycin group experienced more complications but showed a similar mortality rate to the standard therapy group, suggesting that intracolonic vancomycin may impart a protective effect. This study adds further evidence for the need of a randomized controlled study using intracolonic vancomycin as adjunctive therapy in patients presenting with severe CDI. PMID- 27388628 TI - The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine. AB - Conjugation of a small molecule immunopotentiator to antigens has been proposed to deliver the ligand to the receptor, localize its action and minimize systemic inflammation. However, the effect of conjugation of Toll like receptor 7 agonists (TLR7a) on the immunogenicity of carbohydrate-based vaccines is unknown. In this study we synthesized an anti-Neisseria meningitidis serogroup C (MenC) glycoconjugate vaccine composed of MenC oligosaccharide antigens covalently linked to the carrier protein CRM197, to which a TLR7a was in turn conjugated. This vaccine was able to activate in vitro the TLR7 comparably to the unconjugated ligand. The magnitude and the quality of the immune response against MenC capsular polysaccharide were evaluated in mice, comparing the MenC-CRM-TLR7a construct to a MenC-CRM197 vaccine, prepared through the same conjugation chemistry and co-administered with the unconjugated TLR7a. A commercially licensed anti-MenC glycoconjugate was used as further control to determine the influence of the coupling approach and the level of carbohydrate incorporation on the anti-MenC immune response. The possible additive effect of co-administration with Alum hydroxide (AlumOH) was also examined. The bactericidal titers against N. meningitidis were in agreement with the elicited anti-carbohydrate IgGs, and unequivocally showed that TLR7a conjugation to CRM197 enhanced the anti-MenC immune response. TLR7a conjugation induced a shift to a Th1 type response, as assessed by the increased IgG2a subclass production, both in the absence and in the presence of AlumOH. The increased immune response was clearly present only in the absence of AlumOH and was less pronounced than the co-administration of a licensed glycoconjugate with a standard dose of TLR7a-phosphonate adsorbed on the inorganic salt. The amount of MenC saccharide that was covalently linked to CRM197 after previous CRM197-TLR7a conjugation resulted in lower responses than achieved with conventional MenC-CRM197 glycoconjugation in the absence of TLR7a. As result, the benefit of the adjuvant conjugation in terms of anti-MenC immune response was jeopardized by the lower saccharide/protein ratio obtained in the MenC-CRM-TLR7a conjugate. While adsorption on AlumOH offers more flexibility in the administered dose of TLR7a, conjugation of the small molecule immunopotentiator could be particularly suited for vaccination routes such as skin delivery, where insoluble aluminum salts cannot be used because of their reactogenicity in this site. PMID- 27388629 TI - Development of cationic nanocrystals for ocular delivery. AB - A cationic nanocrystal formulation containing dexamethasone acetate nanocrystals (0.05%) and polymyxin B (0.10%) for ophthalmic application was produced using a self-developed small scale method for wet bead milling. The formulation developed offers the advantage of increased saturation solubility of the drug (due to the nano-size of the crystals) and increased residence time in the eye (due to small size and increased mucoadhesion by the cationic charge) resulting ultimately in potential increased bioavailability. Characterization of the nanosuspensions by photon correlation spectroscopy (PCS) and transmission electron microscopy showed that the production method was successful in achieving dexamethasone crystals in the range of about 200-250nm. The physical stabilization of the nanocrystals and generation of the positive charge were realized by using cetylpyridinium chloride (CPC) and benzalkonium chloride (BAC) at the concentration of 0.01%. In contrast to other cationic excipients, they are regulatorily accepted due to their use as preservatives. The drug polymyxin B also contributed to the positive charge. Positive zeta potentials in the range +20 to +30mV were achieved. Isotonicity was adjusted using NaCl and non-ionic excipients (glycerol, sorbitol, dextrose). Physical and chemical stabilities were monitored for a period of 6months at room temperature, 5 degrees C and 40 degrees C. Particle size of the bulk population assessed by PCS remained practically unchanged over 6months of storage for the various formulations without isotonicity agents, and for the CPC-containing formulations with non-ionic isotonicity excipients. The chemical content also proved stable after 6months for all 3 temperatures evaluated. In vitro investigation of mucoadhesion was tested using mucin solutions at different concentrations, and the generated negative zeta potential was used as a measure of the interaction. The zeta potential reversed to about -15mV, indicating distinct interaction. The results show the potential of increased mucoadhesion of such cationic nanocrystals compared to standard eye drop formulations. The positively charged nanocrystal formulation also showed no in vitro cytotoxicity as assessed on fibroblast cell culture. In summary, 3 formulation candidates were identified being a promising alternative for ocular delivery with increased performance compared to what is presently available. PMID- 27388631 TI - Silicon Nanoparticles as Amplifiers of the Ultrasonic Effect in Sonodynamic Therapy. AB - The possibility of using mesoporous silicon nanoparticles as amplifiers (sensitizers) of therapeutic ultrasonic exposure were studied experimentally in vitro and in vivo. The combination of nanoparticles and ultrasound led to a significant inhibition of Hep-2 cancer cell proliferation and Lewis lung carcinoma growth in mice. These results indicated good prospects of using silicon nanoparticles as sensitizers for sonodynamic therapy of tumors. PMID- 27388630 TI - Effect of Hepatitis C Virus Coinfection on the Content of CD4(+) and CD8(+) T Cell Subpopulations in HIV-Infected Patients Receiving Antiretroviral Therapy. AB - We studied the effect of hepatitis C virus coinfection on T cell subpopulations in HIV-infected patients receiving antiretroviral therapy. Coinfection with hepatitis C virus was followed by a decrease in the number of naive CD4(+) T cells and an increase in the count of central CD8(+) memory T cells in these patients. Hepatitis C virus had no effect on the number of CD4(+) memory T cells (main target for HIV). This can explain the absence of strong negative effect of hepatitis C virus on the course of HIV infection. PMID- 27388632 TI - A New Chemiluminescent Method for Evaluation of the Functional Activity of Neutrophils in Patients with Type 2 Diabetes Mellitus. AB - Functional activity of neutrophils was evaluated by the chemiluminescent method with successive double stimulation by soluble stimuli with different mechanisms of action: phorbol-12-myristate-13-acetate (PMA) and phormyl-methionyl-leucyl phenilalanine (fMLP). The study was carried out in 26 patients receiving oral sugar-reducing therapy. In addition to the functional activity of neutrophils, the levels of TBA reactive products, inflammation markers, blood clotting values, and biochemical parameters were measured. The results showed mainly reduction of the granulocytic component of the immune system in the patients. PMID- 27388633 TI - Age-Dependent Changes in Na(+),K(+)-ATPase Activity and Lipid Peroxidation in Membranes of Erythrocytes during Cardiosclerosis Development in Rats. AB - Activity of Na(+),K(+)-ATPase was measured in erythrocyte ghosts of 4- and 12 month-old rats, intact and with postinfarction cardiosclerosis. Enhanced accumulation of secondary LPO products and reduced activity of Na(+),K(+)-ATPase were observed in erythrocyte ghosts of 12-month-old rats. The development of postinfarction cardiosclerosis in 4-month-old rats was accompanied by enhanced accumulation of LPO products and decreased activity of Na(+),K(+)-ATPase. In comparison with young rats with postinfarction cardiosclerosis, 12-month-old rats with this pathology were characterized by less pronounced decrease in Na(+),K(+) ATPase activity and increase in accumulation of LPO products in comparison with intact control. PMID- 27388634 TI - Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice. AB - Current therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical features of MS including relapsing-remitting episodes and secondary-progressive disability. To address the contribution of recurrent inflammatory events and ageing as factors that amplify progressive neurological disease, we examined EAE in 8- to 12-week old and 12-month-old ABH mice. Compared with the relapsing-remitting (RREAE) and secondary progressive (SPEAE) EAE observed in young mice, old mice developed progressive disease from onset (PEAE) associated with pronounced axonal damage and increased numbers of CD3(+) T cells and microglia/macrophages, but not B cells. Whereas the clinical neurological features of PEAE and SPEAE were comparable, the pathology was distinct. SPEAE was associated with significantly reduced perivascular infiltrates and T-cell numbers in the central nervous system (CNS) compared with PEAE and the acute phase of RREAE. In contrast to perivascular infiltrates that declined during progression from RREAE into SPEAE, the numbers of microglia clusters remained constant. Similar to what is observed during MS, the microglia clusters emerging during EAE were associated with axonal damage and oligodendrocytes expressing heat-shock protein B5, but not lymphocytes. Taken together, our data reveal that the course of EAE is dependent on the age of the mice. Younger mice show a relapsing-remitting phase followed by progressive disease, whereas old mice immediately show progression. This indicates that recurrent episodes of inflammation in the CNS, as well as age, contribute to progressive neurological disease. PMID- 27388635 TI - 5-Benzylidene-2,4-thiazolidenedione derivatives: Design, synthesis and evaluation as inhibitors of angiogenesis targeting VEGR-2. AB - A series of novel 5-benzylidene-2,4-thiazolidinediones were designed as inhibitors of angiogenesis targeting VEGFR-2. In docking study, molecules showed similar way of binding with VEGFR-2 as that of the co-crystallized ligand. Compounds were then synthesized, purified and characterized by spectroscopic techniques. Compounds 3f and 3i were found to be most active in the series showing good inhibition of angiogenesis in both CAM and in zebrafish embryo assays. Compound 3i also exhibited IC50 of 0.5MUM against VEGFR-2. PMID- 27388636 TI - Does skill specialisation influence individual differences in drag flicking speed and accuracy? AB - Research has revealed that individual soccer goalkeepers respond differently to penalty shots, depending on their specific perceptual and motor capabilities. However, it remains unclear whether analogous differences exist between individual penalty takers, and if specialising in penalty taking affects the occurrence of differences between individuals. The present study examined individual differences in penalty shot speed and accuracy for specialists in penalty taking versus non-specialists. Expert specialist field hockey drag flickers and equivalently skilled non-specialists performed drag flicks towards predetermined targets placed in the face of a standard field hockey goal. Comparisons in shot speed and accuracy were made at a group level (specialists vs. non-specialists) as well as between individuals. Results revealed differences in both speed and accuracy between specialists, but only differences in speed between non-specialists. Specialists generated significantly greater shot speed than non-specialists (P < .001) and were more accurate to some, but not all, targets (top left, P < .006, bottom left P < .001). In addition, it was found that in specialists increasing practice correlated with decreasing accuracy. This may indicate that excessive practice could potentially reduce a specialist's accuracy in shooting towards specific targets. PMID- 27388637 TI - Enhancing primary care clerkships with virtual patients. AB - BACKGROUND: Virtual patients, computer-assisted patient scenarios, have been used in different medical disciplines over several years. Researchers have already gained knowledge on how it helps foster clinical thinking, fills knowledge gaps and enables patient management. Nonetheless, despite these advances in knowledge, the use of virtual patients in Family Medicine education remains limited. OBJECTIVES: We point out the current knowledge, benefits and potential ways of using virtual patients in the Family Medicine setting. DISCUSSION: Virtual patients can be used as a preparation tool for clinical clerkships as well as learning about patient treatment not usually encountered in every day practice. Regardless of the means of implementation, students benefit from acquiring skills through multifaceted virtual patients. We firmly believe that, when intelligently applied, virtual patients can enhance and improve future Family Medicine education. PMID- 27388638 TI - Investigating lithium-ion battery materials during overcharge-induced thermal runaway: an operando and multi-scale X-ray CT study. AB - Catastrophic failure of lithium-ion batteries occurs across multiple length scales and over very short time periods. A combination of high-speed operando tomography, thermal imaging and electrochemical measurements is used to probe the degradation mechanisms leading up to overcharge-induced thermal runaway of a LiCoO2 pouch cell, through its interrelated dynamic structural, thermal and electrical responses. Failure mechanisms across multiple length scales are explored using a post-mortem multi-scale tomography approach, revealing significant morphological and phase changes in the LiCoO2 electrode microstructure and location dependent degradation. This combined operando and multi-scale X-ray computed tomography (CT) technique is demonstrated as a comprehensive approach to understanding battery degradation and failure. PMID- 27388640 TI - Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats. AB - CONCLUSION: Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. OBJECTIVE: To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. MATERIALS AND METHODS: This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. RESULTS: Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally. PMID- 27388641 TI - Microbial Oxidation of KE-298 Metabolites by Rhizopus sp. and Rhodococcus sp. Strains. AB - The metabolites of the antirheumatic agent KE-298 in humans, (-)-(2R)-M-4 [(-) (2R)-4-(4-hydroxymethylphenyl)-2-methylthiomethyl-4-oxobutanoic acid], (-)-(2R)-M 5 [diastereomers of (-)-(2R)-4-(4-hydroxymethyl-phenyl)-2-methylsulfinyl-methyl-4 oxobutanoic acid], (-)-(2R)-M-6 [(-)-(2R)-4-(4-carboxyphenyl)-2-methylthio-methyl 4-oxobutanoic acid], and (-)-(2R)-M-7 [di- astereomers of (-)-(2R)-4-(4 carboxyphenyl)-2-methyl-sulfinylmethyl-4-oxobutanoic acid] were synthesized based on microbial transformation. The substrate KE-748 (racemic form of (-)-(2R)- and (+)-(2S)-4-(4-methyl-phenyl)-2-methylthiomethyl-4-oxobutanoic acid: 7.5 g) was converted to (-)-(2R)-M-4 (1.84 g) using Rhizopus sp. TF0040 in a 50-l jar fermentor. Specific cytochrome P-450 inhibitors, SKF-525-A and metyrapone strongly inhibited the hydroxylation reaction. It was suggested that cytochrome P 450 is responsible for the microbial reaction. Furthermore, (-)-(2R)-M-4 (200 mg) was transformed to (-)-(2R)-M-6 (144 mg) by co-oxidation with n-hexadecane as a carbon source using Rhodococcus sp. TA0250 in a 1.4-l jar fermentor. Starting from (-)-(2R)-M-4 and (-)-(2R)-M-6 obtained as above, (-)-(2R)-M-5 and (-)-(2R)-M 7, respectively were chemically synthesized by m-chloroperoxybenzoic acid oxidation. PMID- 27388642 TI - Effects of Organic Solvents on Indigo Formation by Pseudomonas sp. strain ST-200 Grown with High Levels of Indole. AB - The indole tolerance level of Pseudomonas sp. strain ST-200 was 0.25 mg/ml. The level was raised to 4 mg/ml when diphenylmethane was added to the medium to 20% by volume. ST-200 grown in this two-phase culture system containing indole (1 mg/ml) and diphenylmethane (0.2 ml/ml) produced a water-soluble yellow pigment, isatic acid, and two water-insoluble and diphenylmethane-soluble pigments, blue indigo and purple indirubin. The amounts of the water-insoluble pigments corresponded to 0.5% (indigo) and 0.2% (indirubin) of the indole added to the medium. Of the conditions tried, indigo and indirubin were formed only when ST 200 was grown in the two-phase system overlaid with organic solvents with appropriate polarity. PMID- 27388639 TI - Peptide conjugated magnetic nanoparticles for magnetically mediated energy delivery to lung cancer cells. AB - AIM: In the present study, we examine the effects of internalized peptide conjugated iron oxide nanoparticles and their ability to locally convert alternating magnetic field (AMF) energy into other forms of energy (e.g., heat and rotational work). MATERIALS & METHODS: Dextran-coated iron oxide nanoparticles were functionalized with a cell penetrating peptide and after internalization by A549 and H358 cells were activated by an AMF. RESULTS: TAT functionalized nanoparticles and AMF exposure increased reactive oxygen species generation compared with the nanoparticle system alone. The TAT-functionalized nanoparticles induced lysosomal membrane permeability and mitochondrial membrane depolarization, but these effects were not further enhanced by AMF treatment. Although not statistically significant, there are trends suggesting an increase in apoptosis via the Caspase 3/7 pathways when cells are exposed to TAT functionalized nanoparticles combined with AMF. CONCLUSION: Our results indicate that internalized TAT-functionalized iron oxide nanoparticles activated by an AMF elicit cellular responses without a measurable temperature rise. PMID- 27388643 TI - Isolation of a Sulfur-oxidizing Bacterium That can Grow under Alkaline pH, from Corroded Concrete. AB - To study the early stages of concrete corrosion by bacteria, sulfur-oxidizing bacterium strain RO-1, which grows in an alkaline thiosulfate medium (pH 10.0) was isolated from corroded concreate and characterized. Strain RO-1 was a Gram negative, rod-shaped bacterium (0.5-0.6*0.9-1.5 MUm). The mean G+C content of the DNA of strain RO-1 was 65.0 mol%. Optimum pH and temperature for growth were 8.0. and 30-37 degrees C, respectively. When grown in thiosulfate medium with pH 10.0, growth rate of the strain was 48% of that observed at the optimum pH for growth. Strain RO-1 used sulfide, thiosulfate, and glucose, but not elemental sulfur or tetrathionate, as a sole energy source. Strain RO-1 grew under anaerobic conditions in pepton-NO3 (-) medium containing sodium nitrate as an electron acceptor, and had enzyme activities that oxidized sulfide, elemental sulfur, thiosulfate, sulfite, and glucose, but not tetrathionate. The bacterium had an activity to assimilate (14)CO2 into the cells when thiosulfate was used as an energy source. These results suggest that strain RO-1 is Thiobacillus versutus. Strain RO-1 exuded Ca(2+) from concrete blocks added to thiosulfate medium with pH 9.0 and the pH of the medium decreased from 9.0 to 5.5 after 22 days of cultivation. In contrast, Thiobacillus thiooxidans strain NB1-3 could not exude Ca(2+) in the same thiosulfate medium, suggesting that strain RO-1, but not T. thiooxidans NB1-3, is involved in the early stage of concrete corrosion because concrete structures just after construction contain calcium hydroxide and have a pH of 12-13. PMID- 27388644 TI - Synthesis and Octopaminergic-agonist Activity of 3-(Substituted Phenyl)imidazolidine-2-thiones and Related Compounds. AB - 3-(Substituted phenyl)imidazolidine-2-thiones (SPITs) and related compounds were synthesized by cyclizing monoethanolamine hydrogen sulfate with arylisothiocyanates in the presence of sodium hydroxide. The activity for stimulating adenylate cyclase prepared from thoracic nerve cords of the American cockroach, Periplaneta americana L., was examined with these compounds. A SPIT with a 2,6-diethylphenyl group (48) was the only full agonist, the other SPIT derivatives being partial agonists. Greater enzyme activation appeared to result from short-chain alkyl rather than halogen substitution at the 2,6-positions of the aromatic ring of SPITs. Increasing the chain length from methyl to ethyl in 2,6-disubstituted SPIT caused an increase in the enzyme activation. Meanwhile, further increase of the chain length from ethyl to isopropyl in 2,6-disubstituted SPIT caused a decrease in the enzyme activation. Superimposition of energy minimized octopamine and 48 revealed structural and conformational similarities that account for the higher Vmax value of 48. There was a marked decrease in the enzyme activation after alkylating at C4 or C5 of the imidazolidine ring of the potent SPITs. Thus, a certain degree of bulkiness and hydrophobicity at the 2- and 6-positions on the phenyl ring of a SPIT and the N-terminal was favorable for activating adenylate cyclase. PMID- 27388645 TI - New Sulfated Oligosaccharides Produced by Pseudomonas beta-Agarase from Gracilaria verrucosa Polysaccharide. AB - Polysaccharide (partially sulfated agarose) with macrophage-stimulation activity, derived from Gracilaria verrucosa, was decomposed by two types of beta-agarase (agarases II and IV) from Pseudomonas sp. O-148. The hydrolysates were fractionated with ethanol precipitation and anion-exchange chromatography. The resulting anionic oligosaccharides with sulfate groups were investigated by (13)C NMR spectroscopy. While the spectra of oligosaccharides produced by agarase IV showed identical patterns with those by beta-agarase I from Pseudomonas atlantica and indicated the location of a sulfated saccharide unit on the non-reducing end, another new type of saccharide was found in the products by agarase II. The novel oligosaccharides by agarase II had a neoagarobiose unit on their non-reducing end and had sulfated units internally. This indicated the novelty of agarase II in cleavage fashion. PMID- 27388646 TI - Development and Application of an Effective Detection Method for Fish Plasma Vitellogenin Induced by Environmental Estrogens. AB - Vitellogenin is a protein induced by estrogens, including environmental chemicals with estrogenic activity. To measure the effects of environmental estogens, we developed an effective and rapid one-step method of detecting and purifying fish plasma vitellogenin using a high-performance anion-exchange chromatography column, POROS-HQ. Vitellogenin in a plasma of estradiol-treated male fish (mummichog and red sea bream) was eluted as a single peak with a retention time of 10 minutes from the column, which gives an almost pure preparation as assessed by SDS-PAGE. The lowest detectable amount of vitellogenin was 2 MUg per assay. The method was used to analyze the plasma vitellogenin level of aquacultured red sea breams caught in August, when the spawning season is over, and usually no vitellogenin is detected in either females or males, physiologically. However, the data showed that in addition to a few females, some male fish synthesized vitellogenin, suggesting that some chemicals or unknown factors with estrogenic activity have induced fish in the ocean to produce vitellogenin. PMID- 27388647 TI - Imidacloprid and Related Compounds: Structure and Water Solubility of N-Alkyl Derivatives of Imidacloprid. AB - An intramolecular hydrogen bond between NH***O2N in insecticide, imidacloprid (1), and its nitromethylene analog 15 was proved by NMR and IR spectra. That electron delocalization over their planar moieties was disrupted by alkylation at the imidazolidine nitrogen atom is demonstrated by the hypsochromic shifts in UV and deshielding effect in NMR spectra. Interestingly, the N-alkyl derivatives (C1 5) had greater water solubility than 1, although increasing alkyl chain length decreased the solubility. The hydrophilicity of the alkyl derivatives would result from remote charge heads being formed as a result of the conjugation disruption by alkylation, while the hydrophobicity of 1 could be ascribed to the charge distribution over the conjugated system coupled with the intramolecular H bonding. The greater water solubility of 15 than 1 and contrastively small solubility of the cyanoimine analogue are discussed based on the difference in their steric crowding. PMID- 27388648 TI - Globulin and Albumin-2 Associated with Protein Bodies in Amaranthus cruentus Seeds. AB - To examine whether albumin-2, a specific protein found only in amaranth seeds so far, is associated with protein bodies, we isolated protein bodies from Amaranthus cruentus seed embryos by rate-zonal centrifugation with a sucrose gradient. Most protein bodies in the final preparation were intact when observed by electron microscopy. Profiles by SDS-PAGE showed that the isolated protein bodies contained globulin and albumin-2. PMID- 27388649 TI - Relationship between Sulfaguanidine Resistance and Increased Cellulose Production in Acetobacter xylinum BPR3001E. AB - The mechanism of the increased cell growth and cellulose production of Acetobacter xylinum subsp. sucrofermentans BPR3001E, a sulfaguanidine (SG) resistant mutant, was investigated. We found that adding p-aminobenzoic acid (PABA) to cultures of the parent strain, BPR2001, led to increased levels of intracellular adenosine-related purine compounds and increased cellulose production. Furthermore, adding ATP increased the cellulose production by permeabilized BPR2001 cells. On the other hand, the intracellular levels of PABA and adenosine-related purine compounds in BPR3001E cells were higher than those in BPR2001 cells. These results suggest that SG resistance increases enhance cellulose production through increased levels of intracellular high-energy compounds caused by increased PABA biosynthesis, reflecting the promoted supply of cellulose precursors. PMID- 27388650 TI - Purification and Some Molecular Properties of Rice Germ Calmodulin. AB - Calmodulin (CaM) from rice germ (Oryza sativa L) was purified to homogeneity by hydrophobic interaction chromatography and gel filtration. The protein showed a single spot by SDS-PAGE. This purified protein had multiple absorption maxima at 276~279, 268, 265, 258, and 253 nm. Like other plant CaM, the protein contained one mole of Tm3Lys, cysteine, and tyrosine, and tryptophan was not detected. Hydrophobic properties of rice germ, spinach, and Neurospora crassa CaM were directly tested by an HPLC method using an ODS-120T column and by a hydropathy plotting method. Obvious hydrophobic differences with rice germ CaM>spinach CaM>N. crassa CaM, were observed among calmodulins from rice germ and others. PMID- 27388651 TI - Convenient Regioselective mono-2-O-Sulfonation of Cyclomaltooctaose. AB - Regioselective mono-2-O-sulfonation of cyclomaltooctaose was conveniently achieved by using the combination of sulfonyl imidazole and molecular sieves in DMF. In this reaction, no 3-O- or 6-O-sulfonation products were produced. The reactions do not require strict anhydrous or basic conditions, or specific sulfonyl groups. PMID- 27388652 TI - Synthesis of Both Enantiomers of 15-Hexadecanolide, a Sex Pheromone Component of the Stink Bug, Piezodorus hybneri. AB - Both enantiomers of 15-hexadecanolide, a sex pheromone component of the stink bug (Piezodorus hybneri), were synthesized by using the Yamaguchi or Mitsunobu macrolactonization reaction of (R)-15-hydroxyhexadecanoic acid prepared from ethyl (R)-beta-hydroxybutyrate in 5 steps. PMID- 27388653 TI - Bio-deposition of Amorphous Silica by an Extremely Thermophilic Bacterium, Thermus spp. AB - The bio-deposition of amorphous silica, which occurred in vitro by exposure to the extremely thermophilic bacterium Thermus spp. began from the latter part of the exponential phase of growth of the bacteria. The concentration with which the deposition occurred exceeded the solubility of amorphous silica of neutral pH at the temperature 60~85 degrees C. Our observations suggest that Thermus spp. promotes the formation of siliceous minerals in a geothermal environment. PMID- 27388654 TI - A possible pathogenetic role of IL-23/IL-17 axis in rheumatoid nodules in patients with rheumatoid arthritis. PMID- 27388655 TI - Nintedanib data challenge IPF guidelines. PMID- 27388656 TI - Determination of chloride in brazilian crude oils by ion chromatography after extraction induced by emulsion breaking. AB - The present paper reports on the development of a novel extraction induced by emulsion breaking (EIEB) method for the determination of chloride in crude oils. The proposed method was based on the formation and breaking of oil-in-water emulsions with the samples and the consequential transference of the highly water soluble chloride to the aqueous phase during emulsion breaking, which was achieved by centrifugation. The determination of chloride in the extracts was performed by ion chromatography (IC) with conductivity detection. Several parameters (oil phase:aqueous phase ratio, crude oil:mineral oil ratio, shaking time and type and concentration of surfactant) that could affect the performance of the method were evaluated. Total extraction of chloride from samples could be achieved when 1.0g of oil phase (0.5g of sample+0.5g of mineral oil) was emulsified in 5mL of a 2.5% (m/v) solution of Triton X-114. The obtained emulsion was shaken for 60min and broken by centrifugation for 5min at 5000rpm. The separated aqueous phase was collected, filtered and diluted before analysis by IC. Under these conditions, the limit of detection was 0.5MUgg(-1) NaCl and the limit of quantification was 1.6MUgg(-1) NaCl. We applied the method to the determination of chloride in six Brazilian crude oils and the results did not differ statistically from those obtained by the ASTM D6470 method when the paired Student-t-test, at 95% confidence level, was applied. PMID- 27388657 TI - Determination of tributyltin in whole water matrices under the European Water Framework Directive. AB - Monitoring of water quality is important to control water pollution. Contamination of the aquatic system has a large effect on human health and the environment. Under the European Water Framework Directive (WFD) 2000/60/EC and the related directive on environmental quality standards (EQS) in the field of water policy 2008/105/EC, the need for sensitive reference methods was highlighted. Since tributyltin (TBT) is one of the WFD listed priority substances a method was developed which is capable to qualify and quantify the pollutant at the required low WFD EQS of 0.2ngL(-1) in whole water bodies, i.e. in non filtered water samples with dissolved organic carbon and suspended particulate matter. Therefore special attention was paid on the interaction of TBT with the suspended particulate matter and humic substances to obtain a complete representation of the pollution in surface waters. Different water samples were investigated varying the content of organic dissolved and suspended matter. Quantification was performed using species-specific isotope dilution (SSID) and gas chromatography with inductively coupled plasma mass spectrometry (GC-ICP-MS). Different sample treatment strategies were evaluated and compared. The process of internal standard addition was investigated and optimized, hence the equilibrium between internal standards and matrix is of primary importance to perform accurate SSID. Samples spiked at EQS level were analyzed with a recovery between 95 and 105 %. Additionally real surface water samples were investigated and the TBT concentration for the whole water body was determined and compared with conventional routine analysis method. PMID- 27388658 TI - The hydrophilicity vs. ion interaction selectivity plot revisited: The effect of mobile phase pH and buffer concentration on hydrophilic interaction liquid chromatography selectivity behavior. AB - This work systematically investigates the selectivity changes on many HILIC phases from w(w)pH 3.7-6.8, at 5 and 25mM buffer concentrations. Hydrophilicity (kcytosine/kuracil) vs. ion interaction (kBTMA/kuracil) selectivity plots developed by Ibrahim et al. (J. Chromatogr. A 1260 (2012) 126-131) are used to investigate the effect of mobile phase changes on the selectivity of 18 HILIC columns from various classes. "Selectivity change plots" focus on the change in hydrophilicity and ion interaction that the columns exhibit upon changing mobile phase conditions. In general, the selectivity behavior of most HILIC columns is dominated by silanol activity. Minimal changes in selectivity are observed upon changing pH between w(w)pH 5 and 6.8. However, a reduction in ionic interaction is observed when the buffer concentration is increased at w(w)pH>=5.0 due to ionic shielding. Reduction of the w(w)pH to<5.0 results in decreasing cation exchange activity due to silanol protonation. Under all eluent conditions, the majority of phases show little change in their hydrophilicity. PMID- 27388659 TI - Selective solid-phase extraction using molecularly imprinted polymers for analysis of venlafaxine, O-desmethylvenlafaxine, and N-desmethylvenlafaxine in plasma samples by liquid chromatography-tandem mass spectrometry. AB - This paper focuses on the development of a novel miniaturized molecularly imprinted solid-phase extraction (MISPE) and ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine venlafaxine (VEN), O-desmethylvenlafaxine (ODV), and N-desmethylvenlafaxine (NDV) in plasma samples. The molecularly imprinted polymer (MIP) was prepared by the precipitation polymerization approach; VEN, metacrylic acid, ethylene glycol dimethacrylate, 2,2-azobisisobutyronitrile, and toluene were used as template, monomer, crosslinker, initiator, and porogen solvent, respectively. MIP and of the non-imprinted control polymer (NIP) sorbents were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. MIP phase presented higher extraction efficiency (MISPE, using plasma samples spiked with VEN) than the NIP phase (84 and 49% recovery rates, respectively). Analysis of other antidepressants with different chemical structures by MISPE-UHPLC-MS/MS attested to the selectivity of the developed MIP. The developed method presented precision assays with coefficients of variation (CV) smaller than 15%; accuracy assays with relative standard error (RSE%) values ranging from -12 to 16%, and linear ranges from 3 to 700ngmL(-1) for VEN, from 5 to 700ngmL(-1) for ODV, and from 3 to 500ngmL(-1) for NDV. The coefficients of determination (r(2)) were higher than 0.995. The lack-of-fit test also attested to the linearity of this method. This method was successfully applied to determine VEN, NDV, and ODV in plasma samples from depressed patients undergoing therapy with VEN. PMID- 27388660 TI - Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials. AB - OBJECTIVE: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED). RESEARCH DESIGN AND METHODS: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (>=18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed. MAIN OUTCOME MEASURES: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0-4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0-4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0 100). RESULTS: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS 1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05-0.65; p = 0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10-0.38; p = 0.0007). Among more symptomatic participants (baseline EDS >=40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35-24.33; nominal p = 0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51 16.70; p < 0.0001). LIMITATIONS: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed. CONCLUSIONS: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED. PMID- 27388661 TI - Postnatal development and histofunctional differentiation of the oviduct in the broad-snouted caiman (Caiman latirostris). AB - Caiman latirostris is a South American crocodilian species characterized as a sentinel of the presence of endocrine-disrupting compounds (EDCs). Evaluating developmental events in hormone-dependent organs, such as the oviduct, is crucial to understand physiological postnatal development, to identify putative periods of exposure sensitive to EDCs, and/or to identify biomarkers useful to evaluate the effects of EDC exposure. In this study, we describe the histomorphological features of C. latirostris oviducts by establishing the ontogeny of changes at cellular, tissue and molecular levels from the neonatal to the pre-pubertal juvenile stages. Since the histological diagnosis of the adenogenic oviduct lies on a group of features, here we defined a histofunctional score system and a cut off value to distinguish between preadenogenic and adenogenic oviducts. Our results showed that the maturation of the C. latirostris oviduct is completed postnatally and characterized by changes that mimic the pattern of histological modifications described for the mammalian uterus. Ontogenic changes in the oviductal epithelium parallel changes at subepithelial level, and include collagen remodeling and characteristic spatial-temporal patterns of alpha-actin and desmin. The expression pattern of estrogen receptor alpha and progesterone receptor evidenced that, even at early postnatal developmental stages, the oviduct of C. latirostris is a target organ of endogenous and environmental hormones. Besides, oviductal adenogenesis seems to be an estrogen-dependent process. Results presented here provide not only insights into the histophysiological aspect of caiman female reproductive ducts but also new tools to better characterize caimans as sentinels of endocrine disruption. PMID- 27388662 TI - Environmental estrogens inhibit mRNA and functional expression of growth hormone receptors as well as growth hormone signaling pathways in vitro in rainbow trout (Oncorhynchus mykiss). AB - Fish in aquatic habitats are exposed to increasing concentrations and types of environmental contaminants, including environmental estrogens (EE). While there is growing evidence to support the observation that endocrine-disrupting compounds (EDCs) possess growth-inhibiting effects, the mechanisms by which these physiological effects occur are poorly understood. In this study, we examined the direct effects of EE, specifically 17beta-estradiol (E2), beta-sitosterol (betaS), and 4-n-nonylphenol (NP), on GH sensitivity as assessed by mRNA expression and functional expression of growth hormone receptor in hepatocytes, gill filaments, and muscle in rainbow trout (Oncorhynchus mykiss). Additionally, we examined the effects of EE on signaling cascades related to growth hormone signal transduction (i.e., JAK-STAT, MAPK, and PI3K-Akt). Environmental estrogens directly suppressed the expression of GHRs in a tissue- and compound-related manner. The potency and efficacy varied with EE; effects were most pronounced with E2 in liver. EE treatment deactivated the JAK-STAT, MAPK, and PI3K-Akt pathways in liver a time-, EE- and concentration-dependent manner. Generally, E2 and NP were most effective in deactivating pathway elements; maximum suppression for each pathway was rapid, typically occurring at 10-30min. The observed effects occurred via an estrogen-dependent pathway, as indicated by treatment with an ER antagonist, ICI 182,780. These findings suggest that EEs suppress growth by reducing GH sensitivity in terms of reduced GHR synthesis and reduced surface GHR expression and by repressing GH signaling pathways. PMID- 27388663 TI - Participation of the extrinsic cholinergic innervation in the action of nitric oxide on the ovarian steroidogenesis in the first proestrous in rats. AB - An ex-vivo Coeliac Ganglion-Superior Ovarian Nerve-Ovary (CG-SON-O) system and an ovary without peripheral neural influence from virgin rats in the first proestrous were used to test whether ovarian extrinsic innervation and nitric oxide (NO) affects steroidogenesis in the ovary. The CG and the ovary were placed in separate buffered-compartments, connected by the SON. Stimulation of the CG was achieved by 10(-6)M acetylcholine (Ach). The ovary without peripheral neural influence was placed alone in a buffered-compartment. To test a possible role of NO in the ovarian response to peripheral neural influence, 100MUM sodium nitroprusside (SNP, an NO donor) and 100MUM N(G)-nitro-l-arginine methyl ester (l NAME, an inhibitor of NO synthase) were added to the ovarian compartment separately. In the CG-SON-O system, SNP into the ovarian compartment increased the concentration of NO, reduced the release of progesterone and increased the release of estradiol (E2), increasing the mRNAs related to their synthesis enzyme. The addition of l-NAME to the ovarian compartment caused an opposite effect. In the ovary alone, NO manifested an antisteroidogenic effect on both hormones. These results show that the ovarian extrinsic innervation maintains a direct relationship between NO and E2, both needed at high levels during the follicular phase, allowing the continuity of the estrous cycle. PMID- 27388664 TI - "Almost There": The Princess and the Frog Song. PMID- 27388665 TI - The Remarkable 50 Years of Imaging in HCM and How it Has Changed Diagnosis and Management: From M-Mode Echocardiography to CMR. AB - The almost 50-year odyssey of cardiac imaging in hypertrophic cardiomyopathy (HCM), revisited and described here, has been remarkable, particularly when viewed in the timeline of advances that occurred during a single generation of investigators. At each step along the way, from M-mode to 2-dimensional echocardiography to Doppler imaging, and finally over the last 10 years with the emergence of high-resolution tomographic cardiac magnetic resonance (CMR), evolution of the images generated by each new technology constituted a paradigm change over what was previously available. Together, these advances have transformed the noninvasive diagnosis and management of HCM in a number of important clinical respects. These changes include a more complete definition of the phenotype, resulting in more reliable clinical identification of patients and family members, defining mechanisms (and magnitude) of left ventricular outflow obstruction, and novel myocardial tissue characterization (including in vivo detection of fibrosis/scarring); notably, these advances afford more precise recognition of at-risk patients who are potential candidates for life-saving primary prevention defibrillator therapy. This evolution in imaging as applied to HCM has indelibly changed cardiovascular practice for this morphologically and clinically complex genetic disease. PMID- 27388666 TI - Multimodality Imaging for Guiding EP Ablation Procedures. AB - Recent advances in 3-dimensional electroanatomical mapping have been met by continuous improvements in the field of cardiac imaging and image integration during ablation procedures. Echocardiography, computed tomography, cardiac magnetic resonance, and nuclear imaging provide information about cardiac anatomy and ultrastructure of the heart that may be crucial for a successful ablation procedure. Techniques and value of pre-procedural, intraprocedural, and post procedural imaging and image integration are discussed in this review article. Pre-procedural imaging provides key anatomic information that can be complemented by intraprocedural imaging to minimize procedural complications. Furthermore, the presence and extent of structural heart disease can be assessed pre-procedurally and can be displayed intraprocedurally to limit and focus the mapping and ablation procedure to the area of interest. Pre-procedural imaging combined with imaging obtained during the ablation procedure further enhances procedural safety, reduces exposure to ionizing radiation from fluoroscopy, reduces procedure time, and may improve outcomes. PMID- 27388667 TI - Proliferation of Coronary Adventitial Vasa Vasorum in Patients With Spontaneous Coronary Artery Dissection. PMID- 27388668 TI - MDCT for Cardiovascular Evaluation: Are There 2 "One-Stop Shops"? PMID- 27388669 TI - Abeta41 Aggregates More Like Abeta40 than Like Abeta42: In Silico and in Vitro Study. AB - Formation of intracellular plaques and small oligomeric species of amyloid beta (Abeta) peptides inside neurons is a hallmark of Alzheimer's disease. The most abundant Abeta species in the brain are Abeta1-40 and Abeta1-42, which are composed, respectively, of 40 and 42 residues. Abeta1-42 differs from Abeta1-40 only in two residues, Ile41 and Ala42, yet it shows remarkably faster aggregation and greater neurotoxicity than Abeta1-40. Thus, it is crucial to understand the relative contributions of Ile41 and Ala42 to these distinct behaviors. To achieve this, secondary structures of the Abeta1-41 monomer, which contribute to aggregation propensity, were studied by all-atom molecular dynamics simulation in an implicit solvent and compared to those of Abeta1-40 and Abeta1-42. We find that the secondary structure populations of Abeta1-41 are much closer to those of Abeta1-40 than to those of Abeta1-42, suggesting that Abeta1-41 and Abeta1-40 are likely to have similar aggregation properties. This prediction was confirmed through a thioflavin-T aggregation assay. Thus, our finding indicates that the hydrophobic residue at position 42 is the major contributor to the increased fibril formation rates and consequently neurotoxicity of Abeta peptides. PMID- 27388670 TI - Upper Antero-Medial Thigh as an Alternative Site for Implantation of Intrathecal Pumps: A Case Series. AB - INTRODUCTION: Neuraxial drug delivery via intrathecal drug delivery systems (IDDS) is becoming an increasingly common mode of treating intractable cancer related pain, chronic pain, or severe spasticity. An implanted infusion pump delivers medication into the intrathecal (subarachnoid) space via a thin catheter. These pumps are commonly placed in the anterior abdominal wall. Certain conditions may render it difficult or unsafe for an IDDS to be implanted at the traditional site; thus, alternative sites have been explored. We report on the use of the upper antero-medial thigh as a safe alternative site for this purpose. METHODS AND MATERIALS: Nine patients between 22 and 69 years of age underwent placement of an IDDS infusion pump in the upper antero-medial aspect of one thigh. In each patient, the anterior abdominal wall was precluded for implantation due to various reasons, such as extensive abdominal scar tissue from previous surgeries, placement of feeding tubes and ostomies, large ventral hernia or metastatic masses protruding from the abdomen. RESULTS: Nine patients, with ages ranging from 22 to 69 years old, had IDDS implantation in the upper thigh. The first patient experienced wound dehiscence (antero-lateral location) and after explantation, another pump was placed successfully in the opposite thigh (antero-medial location). One patient has had pump replacement due to end-of battery life. She also needed an unrelated catheter revision. Seven patients have expired from their disease progression after living for an average of 142.7 days (range 50 days to 354 days) while two patients continue to experience relief from pain and spasticity years later (see Table 1). No neurovascular damage, infections, or other complications occurred in our series. CONCLUSION: The upper antero-medial thigh is a safe alternative to the anterior abdominal wall for implantation of an IDDS. PMID- 27388671 TI - Stratified analysis of 800 Asian patients after robot-assisted radical prostatectomy with a median 64 months of follow up. AB - OBJECTIVE: To report the 5-year oncological outcomes of robot-assisted radical prostatectomy from the largest series ever reported from Asia. METHODS: A retrospective analysis of 800 Asian patients who were treated with robot-assisted radical prostatectomy from July 2005 to May 2010 in the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea was carried out. The primary end-point was to evaluate the biochemical recurrence. The secondary end-point was to show the biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival. RESULTS: A total of 197 (24.65%), 218 (27.3%), and 385 (48.1%) patients were classified as low-, intermediate- and high-risk patients according to the D'Amico risk stratification risk criteria, respectively. The median follow-up period was 64 months (interquartile range 28-71 months). The overall incidence of positive surgical margin was 36.6%. There was biochemical recurrence in 183 patients (22.9%), 38 patients (4.8%) developed distant metastasis and 24 patients (3%) died from prostate cancer. Actuarial biochemical recurrence-free survival, metastasis-free survival, and cancer-specific survival rates at 5 years were 76.4%, 94.6% and 96.7%, respectively. Positive lymph node was associated with lower 5-year biochemical recurrence-free survival (9.1%), cancer-specific survival (75.7%) and metastasis-free survival (61.9%) rates (P < 0.001). On multivariable analysis, among all the predictors, positive lymph node was the strongest predictor of biochemical recurrence, cancer-specific survival and metastasis-free survival (P < 0.001). CONCLUSIONS: Herein we report the largest robot-assisted radical prostatectomy series from Asia. Robot-assisted radical prostatectomy is confirmed to be an oncologically safe procedure that is able to provide effective 5-year cancer control, even in patients with high-risk disease. PMID- 27388672 TI - Whole blood expression profiling from the TREAT trial: insights for the pathogenesis of polyarticular juvenile idiopathic arthritis. AB - BACKGROUND: The Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT trial) was accompanied by a once-in-a-generation sample collection for translational research. In this paper, we report the results of whole blood gene expression analyses and genomic data-mining designed to cast light on the immunopathogenesis of polyarticular juvenile idiopathic arthritis (JIA). METHODS: TREAT samples and samples from an independent cohort were analyzed on Affymetrix microarrays and compared to healthy controls. Data from the independent cohort were used to validate the TREAT data. Pathways analysis was used to characterize gene expression profiles. Furthermore, we correlated differential gene expression with new information about functional regulatory elements within the genome to develop models of aberrant gene expression in JIA. RESULTS: There was a strong concordance in gene expression between TREAT samples and the independent cohort. In addition, rheumatoid factor (RF)-positive and RF negative patients showed only small differences on whole blood expression profiles. Analysis of the combined samples showed 158 genes represented by 176 probes that showed differential expression between TREAT subjects at baseline and healthy controls. None of the differentially expressed genes were encoded within linkage disequilibrium blocks containing single nucleotide polymorphisms known to be associated with risk for JIA. Functional analysis of these genes showed functional associations with multiple processes associated with innate and adaptive immunity, and appeared to reflect overall suppression of STAT1 3/interferon response factor-mediated pathways. CONCLUSIONS: Despite their limitations, whole blood expression profiles clearly distinguish children with polyarticular JIA from healthy controls. Whole blood expression profiles identify several immunologic pathways of biologic relevance that will need to be pursued in homogeneous cell populations in order to clarify mechanisms of pathogenesis. TRIAL REGISTRATION: ClinicalTrials.gov registry #NCT00443430 , originally registered 2 March 2007 and last updated 30 May 2013. PMID- 27388673 TI - Effect of oilseed type on milk fatty acid composition of individual cows, and also bulk tank milk fatty acid composition from commercial farms. AB - Supplementing dairy cow diets with oilseed preparations has been shown to replace milk saturated fatty acids (SFA) with mono- and/or polyunsaturated fatty acids (MUFA, PUFA), which may reduce risk factors associated with cardio-metabolic diseases in humans consuming milk and dairy products. Previous studies demonstrating this are largely detailed, highly controlled experiments involving small numbers of animals, but in order to transfer this feeding strategy to commercial situations further studies are required involving whole herds varying in management practices. In experiment 1, three oilseed supplements (extruded linseed (EL), calcium salts of palm and linseed oil (CPLO) and milled rapeseed (MR)) were included in grass silage-based diets formulated to provide cows with ~350 g oil/day, and compared with a negative control (Control) diet containing no supplemental fat, and a positive control diet containing 350 g/cow per day oil as calcium salt of palm oil distillate (CPO). Diets were fed for 28-day periods in a 5*4 Latin Square design, and milk production, composition and fatty acid (FA) profile were analysed at the end of each period. Compared with Control, all lipid supplemented diets decreased milk fat SFA concentration by an average of 3.5 g/100 g FA, by replacement with both cis- and trans-MUFA/PUFA. Compared with CPO, only CPLO and MR resulted in lower milk SFA concentrations. In experiment 2, 24 commercial dairy farms (average herd size+/-SEM 191+/-19.3) from the south west of the United Kingdom were recruited and for a 1 month period asked to supplement their herd diets with either CPO, EL, CPLO or MR at the same inclusion level as the first study. Bulk tank milk was analysed weekly to determine FA concentration by Fourier Transform mid-IR spectroscopy prediction. After 4 weeks, EL, CPLO and MR all decreased herd milk SFA and increased MUFA to a similar extent (average 3.4 and +2.4 g/100 g FA, respectively) when compared with CPO. Differing responses observed between experiments 1 and 2 may be due in part to variations in farm management conditions (including basal diet) in experiment 2. This study demonstrates the importance of applying experimental research into commercial practice where variations in background conditions can augment different effects to those obtained under controlled conditions. PMID- 27388674 TI - Probiotics for the management of type 2 diabetes mellitus: A systematic review and meta-analysis. AB - AIMS: To systematically review evidence of probiotic interventions against type 2 diabetes mellitus (T2DM) and analyse the effects of probiotics on glycaemic control among T2DM patients. METHODS: Electronic search using five electronic databases was performed until October 2015. Relevant studies were identified, extracted and assessed for risk of bias. The primary outcomes of this review were glycated haemoglobin (HbA1c) and fasting blood glucose (FBG). Fasting plasma insulin, homeostasis model assessment-insulin resistance, C-reactive protein, interleukin-6 and malondialdehyde, were identified as the secondary outcomes. Mean differences (MD) between probiotics and control groups for all outcomes were pooled using either Fixed- or Random-Effect Model. Statistical heterogeneity was assessed using I(2) and Chi(2) tests. RESULTS: Six randomised controlled trials (RCTs) were included in the systematic review, whereas only five were included in meta-analysis. Most RCTs were presented with low or unclear risk of bias. When compared to placebo, FBG was significantly lower with probiotic consumption (MD= 0.98mmol/L; 95% CI: -1.17, 0.78, p<0.00001), with moderate but insignificant heterogeneity noted. Insignificant changes between the groups were also noted for HbA1c and other secondary outcomes. CONCLUSIONS: A moderate hypoglycaemic effect of probiotics, with a significantly lower FBG was noted. Findings on HbA1c, anti inflammatory and anti-oxidative effects of probiotics in the clinical setting, however, remain inconsistent. The findings imply the need for well-designed clinical studies to further assess the potential beneficial effects of probiotics in management of T2DM. PMID- 27388675 TI - The effect of dipeptidyl peptidase-IV inhibition on circulating T cell subpopulations in patients with type 2 diabetes mellitus. AB - AIM: To assess intraindividually the effects of DPP-IV inhibition on the subpopulations of immune cells in type 2 diabetes mellitus (DM2) patients during the course of treatment with sitagliptin. METHODS: In this open label non randomized observational study with a control group DM2 patients were examined before the initiation of the DPP-IV inhibitor administration (sitagliptin 100mg once daily) and then after 4weeks and 12months. Inhibition of the blood plasma DPP-IV enzymatic activity was determined by a chromogenic assay, the immunophenotyping of the blood cell subpopulations was performed using flow cytometry and blood plasma cytokine concentrations were quantified using an array based multiplex ELISA. All parameters were evaluated in relation to the entry values in individual patients. RESULTS: The blood plasma DPP-IV enzymatic activity was effectively inhibited during the sitagliptin treatment. A significant decrease of the proportion of Treg cells (to 86+/-31% (median+/-SD) of entry values, p=0.001) and an increase of Th1 cells (to 120+/-103% (median+/ SD) of entry values, p=0.004) were observed after 4weeks but not after one year of the sitagliptin treatment. No changes were observed in the ratio of CD4(+)/CD8(+) cells, in the quantity of NK and Th2 cells and blood plasma cytokine levels. CONCLUSIONS: Sitagliptin treatment may cause temporary changes of the proportion of lymphocyte subpopulations in patients with DM2. The consequent deregulation of the immune system should be considered as a possible cause of the eventual side effects of long term DPP-IV inhibition. PMID- 27388676 TI - 3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product. AB - In vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21st Century - a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impact of 3R4F smoke was substantially greater than that of THS2.2 aerosol in terms of cytotoxicity levels, alterations in tissue morphology, secretion of pro-inflammatory mediators, impaired ciliary function, and increased perturbed transcriptomes and miRNA expression profiles. PMID- 27388677 TI - The role of the FTD-ALS associated C9orf72 expansion in suicide victims. AB - Impulsive and aggressive traits are not only common features displayed by patients with behavioural variant frontotemporal dementia (bvFTD), they may well be the first clinical manifestations of the disease. In addition, suicidal behaviour has been postulated to be a symptom of bvFTD. A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) is the major genetic cause for familial bvFTD. During recent years, several genetic factors predisposing to suicide have been identified, but there are no previous studies analysing the role of the C9orf72 expansion in suicides. In the present study, we aimed to analyse the prevalence of the C9orf72 expansion in unselected suicide victims. The prevalence of the C9orf72 expansion was analysed in a cohort of 109 Finnish victims of suicide (mean age at death 46.1 years; range 18-86 years). The C9orf72 expansion was analysed from the post mortem blood samples. Results showed that no abnormal length C9orf72 expansions were detected in the study cohort. In conclusion, even though suicidal behaviour may be encountered in bvFTD patients, the C9orf72 expansion is not a common genetic finding in unselected suicide victims. PMID- 27388678 TI - Why might regional vaccinology networks fail? The case of the Dutch-Nordic Consortium. AB - We analyzed an attempt to develop and clinically test a pneumococcal conjugate vaccine for the developing world, undertaken by public health institutions from the Netherlands, Sweden, Denmark, Norway and Finland: the Dutch Nordic Consortium (DNC), between 1990 and 2000. Our review shows that the premature termination of the project was due less to technological and scientific challenges and more to managerial challenges and institutional policies. Various impeding events, financial and managerial challenges gradually soured the initially enthusiastic collaborative spirit until near the end the consortium struggled to complete the minimum objectives of the project. By the end of 1998, a tetravalent prototype vaccine had been made that proved safe and immunogenic in Phase 1 trials in adults and toddlers in Finland. The planned next step, to test the vaccine in Asia in infants, did not meet approval by the local authorities in Vietnam nor later in the Philippines and the project eventually stopped.The Dutch DNC member, the National Institute of Public Health and the Environment (RIVM) learned important lessons, which subsequently were applied in a following vaccine technology transfer project, resulting in the availability at affordable prices for the developing world of a conjugate vaccine against Haemophilus influenzae type b. We conclude that vaccine development in the public domain with technology transfer as its ultimate aim requires major front-end funding, committed leadership at the highest institutional level sustained for many years and a competent recipient-manufacturer, which needs to be involved at a very early stage of the development.At the national level, RIVM's policy to consolidate its national manufacturing task through securing a key global health position in support of a network of public vaccine manufacturers proved insufficiently supported by the relevant ministries of the Dutch government. Difficulties to keep up with high costs, high-risk innovative vaccine development and production in a public sector setting led to the gradual loss of production tasks and to the 2009 Government decision to privatize the vaccine production tasks of the Institute. PMID- 27388679 TI - Experiences of Couples Caring for a Child Born with Cleft Lip and/or Palate: Impact of the Timing of Diagnosis. AB - Raising a child born with cleft lip and/or palate (CL/P) can be challenging for parents. Few researchers have examined how having a child born with CL/P impacts couples. The purpose of this descriptive qualitative study was to examine how a child's CL/P diagnosis affects couples' relational adjustment and coping. We conducted interviews with 17 couples (10 prenatal and seven postnatal) caring for children born with CL/P. After conducting thematic content analysis, six overarching themes emerged: (a) relationship growth, (b) challenges, (c) roles and responsibilities, (d) sources of support, (e) talking about cleft, and (f) lessons learned. Findings suggest that couples should be routinely assessed for psychosocial issues and prevention programs should be tailored to preexisting stressors and timing of the diagnosis. PMID- 27388680 TI - eIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and Is Modulated by Phosphorylation. AB - Eukaryotic initiation factor 4A (eIF4A) is a highly conserved RNA-stimulated ATPase and helicase involved in the initiation of messenger RNA translation. Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. Here, we show that this interaction occurs only in proliferating cells where the two proteins coassociate with 5'-cap binding protein complexes, eIF4F or the plant-specific eIFiso4F. CDKA phosphorylates eIF4A on a conserved threonine residue (threonine-164) within the RNA-binding motif 1b TPGR. In vivo, a phospho-null (APGR) variant of the Arabidopsis (Arabidopsis thaliana) eIF4A1 protein retains the ability to functionally complement a mutant (eif4a1) plant line lacking eIF4A1, whereas a phosphomimetic (EPGR) variant fails to complement. The phospho-null variant (APGR) rescues the slow growth rate of roots and rosettes, together with the ovule-abortion and late-flowering phenotypes. In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. These observations suggest a mechanism whereby CDK phosphorylation has the potential to down-regulate eIF4A activity and thereby affect translation. PMID- 27388681 TI - Cytokinin Regulates the Etioplast-Chloroplast Transition through the Two Component Signaling System and Activation of Chloroplast-Related Genes. AB - One of the classical functions of the plant hormone cytokinin is the regulation of plastid development, but the underlying molecular mechanisms remain elusive. In this study, we employed a genetic approach to evaluate the role of cytokinin and its signaling pathway in the light-induced development of chloroplasts from etioplasts in Arabidopsis (Arabidopsis thaliana). Cytokinin increases the rate of greening and stimulates ultrastructural changes characteristic for the etioplast to-chloroplast transition. The steady-state levels of metabolites of the tetrapyrrole biosynthesis pathway leading to the production of chlorophyll are enhanced by cytokinin. This effect of cytokinin on metabolite levels arises due to the modulation of expression for chlorophyll biosynthesis genes such as HEMA1, GUN4, GUN5, and CHLM Increased expression of HEMA1 is reflected in an enhanced level of the encoded glutamyl-tRNA reductase, which catalyzes one of the rate limiting steps of chlorophyll biosynthesis. Mutant analysis indicates that the cytokinin receptors ARABIDOPSIS HIS KINASE2 (AHK2) and AHK3 play a central role in this process. Furthermore, the B-type ARABIDOPSIS RESPONSE REGULATOR1 (ARR1), ARR10, and ARR12 play an important role in mediating the transcriptional output during etioplast-chloroplast transition. B-type ARRs bind to the promotors of HEMA1 and LHCB6 genes, indicating that cytokinin-dependent transcription factors directly regulate genes of chlorophyll biosynthesis and the light harvesting complex. Together, these results demonstrate an important role for the cytokinin signaling pathway in chloroplast development, with the direct transcriptional regulation of chlorophyll biosynthesis genes as a key aspect for this hormonal control. PMID- 27388683 TI - Acute kidney injury: Renal disease in the ICU. AB - Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine - the most common marker of AKI - should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a "static" disease to being a "dynamic process" that requires continuous evaluation of kidney function adapted to the reality of the ICU patient. PMID- 27388682 TI - Polypeptide Transport-Associated Domains of the Toc75 Channel Protein Are Located in the Intermembrane Space of Chloroplasts. AB - Toc75 is the channel for protein translocation across the chloroplast outer envelope membrane. Toc75 belongs to the Omp85 protein family and consists of three N-terminal polypeptide transport-associated (POTRA) domains that are essential for the functions of Toc75, followed by a membrane-spanning beta-barrel domain. In bacteria, POTRA domains of Omp85 family members are located in the periplasm, where they interact with other partner proteins to accomplish protein secretion and outer membrane protein assembly. However, the orientation and therefore the molecular function of chloroplast Toc75 POTRA domains remain a matter of debate. We investigated the topology of Toc75 using bimolecular fluorescence complementation and immunogold electron microscopy. Bimolecular fluorescence complementation analyses showed that in stably transformed plants, Toc75 N terminus is located on the intermembrane space side, not the cytosolic side, of the outer membrane. Immunogold labeling of endogenous Toc75 POTRA domains in pea (Pisum sativum) and Arabidopsis (Arabidopsis thaliana) confirmed that POTRA domains are located in the intermembrane space of the chloroplast envelope. PMID- 27388684 TI - A Model Study of In Silico Proficiency Testing for Clinical Next-Generation Sequencing. AB - CONTEXT: -Most current proficiency testing challenges for next-generation sequencing assays are methods-based proficiency testing surveys that use DNA from characterized reference samples to test both the wet-bench and bioinformatics/dry bench aspects of the tests. Methods-based proficiency testing surveys are limited by the number and types of mutations that either are naturally present or can be introduced into a single DNA sample. OBJECTIVE: -To address these limitations by exploring a model of in silico proficiency testing in which sequence data from a single well-characterized specimen are manipulated electronically. DESIGN: -DNA from the College of American Pathologists reference genome was enriched using the Illumina TruSeq and Life Technologies AmpliSeq panels and sequenced on the MiSeq and Ion Torrent platforms, respectively. The resulting data were mutagenized in silico and 26 variants, including single-nucleotide variants, deletions, and dinucleotide substitutions, were added at variant allele fractions (VAFs) from 10% to 50%. Participating clinical laboratories downloaded these files and analyzed them using their clinical bioinformatics pipelines. RESULTS: Laboratories using the AmpliSeq/Ion Torrent and/or the TruSeq/MiSeq participated in the 2 surveys. On average, laboratories identified 24.6 of 26 variants (95%) overall and 21.4 of 22 variants (97%) with VAFs greater than 15%. No false positive calls were reported. The most frequently missed variants were single nucleotide variants with VAFs less than 15%. Across both challenges, reported VAF concordance was excellent, with less than 1% median absolute difference between the simulated VAF and mean reported VAF. CONCLUSIONS: -The results indicate that in silico proficiency testing is a feasible approach for methods-based proficiency testing, and demonstrate that the sensitivity and specificity of current next-generation sequencing bioinformatics across clinical laboratories are high. PMID- 27388685 TI - Corrigendum to "The incidence, age at diagnosis of breast cancer in Iraqi Kurdish population and comparison to some other countries in Middle-East and West" [Int. J. Surg. 13 (2015) 71-75]. PMID- 27388686 TI - Lateralized antennal control of aggression and sex differences in red mason bees, Osmia bicornis. AB - Comparison of lateralization in social and non-social bees tests the hypothesis that population-level, directional asymmetry has evolved as an adjunct to social behaviour. Previous research has supported this hypothesis: directional bias of antennal use in responding to odours and learning to associate odours with a food reward is absent in species that feed individually, such as mason bees, whereas it is clearly present in eusocial honeybees and stingless bees. Here we report that, when mason bees engage in agonistic interactions, a species-typical interactive behaviour, they do exhibit a directional bias according to which antenna is available to be used. Aggression was significantly higher in dyads using only their left antennae (LL) than it was in those using only their right antennae (RR). This asymmetry was found in both males and females but it was stronger in females. LL dyads of a male and a female spent significantly more time together than did other dyadic combinations. No asymmetry was present in non aggressive contacts, latency to first contact or body wiping. Hence, population level lateralization is present only for social interactions common and frequent in the species' natural behaviour. This leads to a refinement of the hypothesis linking directional lateralization to social behaviour. PMID- 27388687 TI - Quality of life in patients with adrenal insufficiency correlates stronger with hydrocortisone dosage, than with long-term systemic cortisol levels. AB - In patients with adrenal insufficiency (AI) a higher hydrocortisone intake has been associated with more impairment in quality of life (QoL). Irrespective of age, sex and severity of AI the dosage of hydrocortisone is titrated around 20mg/D in all patients with AI based on physical and mental signs and symptoms. However, until now it is unknown whether these QoL impairments are related to increased systemic cortisol exposure. Measurement of hair cortisol levels (CORThair) can be used to assess chronic systemic cortisol exposure. This study aimed to explore whether QoL in patients with AI is associated with CORThair and daily hydrocortisone intake. We performed a cross-sectional study in 120 patients with AI on stable hydrocortisone replacement, in whom hair samples and QoL data were collected. CORThair were measured with ELISA, and QoL was assessed with validated questionnaires (SF-36, EQ-5D, HADS, MFI-20). Patients reported impairments in 14 of 15 QoL subscales (p<0.001). More impairments in physical aspects of QoL correlated with higher CORThair and higher daily hydrocortisone intake (p<0.05), an effect that was more pronounced in female patients. Regression analyses including both CORThair and hydrocortisone intake revealed a significant negative contribution of higher hydrocortisone intake on physical aspects of QoL (p<=0.046), whereas no significant contribution was found for CORThair. The present study showed that patients with AI report several impairments in QoL which are associated with hydrocortisone intake, and to a lesser extent reflected by chronic systemic cortisol exposure as measured by hair cortisol. This suggests that QoL impairments in patients with AI are not per se the effect of prolonged exposure to elevated systemic cortisol levels. PMID- 27388689 TI - Pyrrolizidine Alkaloid-Protein Adducts: Potential Non-invasive Biomarkers of Pyrrolizidine Alkaloid-Induced Liver Toxicity and Exposure. AB - Pyrrolizidine alkaloids (PAs) are phytochemicals present in hundreds of plant species from different families widely distributed in many geographical regions around the world. PA-containing plants are probably the most common type of poisonous plants affecting livestock, wildlife, and humans. There have been many large-scale human poisonings caused by the consumption of food contaminated with toxic PAs. PAs require metabolic activation to generate pyrrolic metabolites to exert their toxicity. In this study, we developed a novel method to quantify pyrrole-protein adducts present in the blood. This method involves the use of AgNO3 in acidic ethanol to cleave the thiol linkage of pyrrole-protein (DHP protein) adducts, and the resulting 7,9-di-C2H5O-DHP is quantified by HPLC-ES MS/MS multiple reaction monitoring analysis in the presence of a known quantity of isotopically labeled 7,9-di-C2D5O-DHP internal standard. Using this method, we determined that diester-type PAs administered to rats produced higher levels of DHP-protein adducts than other types of PAs. The results suggest that DHP-protein adducts can potentially serve as minimally invasive biomarkers of PA exposure. PMID- 27388688 TI - Sex differences in morning cortisol in youth at ultra-high-risk for psychosis. AB - Research suggests abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function play an important role in the pathophysiology of psychosis. However, there is limited research on the biological stress system in young people at ultra high risk (UHR) for psychosis. Morning cortisol levels are particularly relevant to study in this context, as these markers reflect HPA regulation. This is the first examination of sex differences in morning cortisol levels in UHR individuals. Twenty-eight UHR and 22 matched healthy control participants were assessed in respect to symptoms and had home-based collection of salivary cortisol over three time points in the morning. It was predicted that the UHR participants would exhibit lower morning cortisol levels and lower cortisol would be associated with greater symptomatology (i.e. higher positive, negative, and depressive symptoms). Additionally, sex differences in morning cortisol levels were explored based on recent evidence suggesting that sex differences may play an important role in the exacerbation of psychosis. While there were no group differences in morning salivary cortisol secretion, there was a sex by time interaction among UHR individuals, such that only UHR males exhibited flat cortisol levels across two hours after awakening, whereas UHR females had a pattern of cortisol secretion similar to healthy controls, even among medication free individuals (F=6.34, p=0.004). Cortisol AUC (area under the curve) across the three time points had a trend association (medium effect size; r=0.34, p=0.08) with depressive, but not positive or negative, symptom severity. These results stress the importance of considering sex differences in the psychosis risk period, as they improve understanding of pathogenic processes. PMID- 27388690 TI - Incidence of malignancies in patients with juvenile idiopathic arthritis: A retrospective single-center cohort study in Germany. AB - OBJECTIVES: In recent years, concern has been raised about Juvenile Idiopathic Arthritis (JIA) that it could be associated with an increased risk for malignancies. Therefore, the cancer incidence in the JIA patients was evaluated and compared to the cancer incidence in the German population. METHODS: A retrospective single-center hospital-based cohort study was performed using data on the JIA patients treated between 1952 and 2010 at the German Center for Pediatric and Adolescent Rheumatology (GCPAR) (Garmisch-Partenkirchen, Germany). Self-administered standardized questionnaires were sent out in 2012. Standardized incidence ratios (SIRs) and their corresponding 95% confidence intervals (95%CIs) were calculated. RESULTS: The study cohort consisted of 3691 JIA patients, and the response rate was 66%. Patients age ranged from 3 to 73 years of which 64% were female. Total follow-up time was 60,075 person-years; a history of malignancy was reported by 47 patients. Most common types of cancer were melanoma (n = 11), cervical cancer (n = 8) and breast cancer (n = 7). The overall SIR for women was 1.19 (95%CI: 0.77; 1.60) and for men was 0.67 (95%CI: 0.27; 1.07). The SIR for melanoma was 3.21 (95%CI: 1.60; 5.73) in women, whereas in men no melanoma cases were observed. CONCLUSION: Although no overall increased cancer risk was found, results suggest that the risk of melanoma might be increased in female JIA patients. PMID- 27388691 TI - A Systematic Review of the Literature on Posttraumatic Stress Disorder in Victims of Terrorist Attacks. AB - This article was aimed at systematically reviewing the literature on posttraumatic stress disorder (PTSD) among victims of terrorist attacks. Electronic and hand searches of the literature identified 35 studies addressing PTSD prevalence based on validated diagnostic interviews. Overall, in the year after terrorist attacks, 33% to 39% of direct victims developed PTSD, whereas the percentage of indirect victims with PTSD was lower (4% in the affected community, 5%-6% among emergency, rescue, and recovery workers, and 17%-29% among relatives and friends of the injured or killed victims), but nonetheless above the prevalence in the general population. With the passing of time, a significant reduction of PTSD can be expected in the affected community and in the emergency and rescue personnel, but not in the injured victims, in the relatives and friends of the injured or killed victims, and in nontraditional, more vulnerable disaster workers. The implications of these results for the psychological treatment of terrorism victims are discussed. PMID- 27388693 TI - Prediction of CYP2D6 phenotype from genotype across world populations. AB - PURPOSE: Owing to its highly polymorphic nature and major contribution to the metabolism and bioactivation of numerous clinically used drugs, CYP2D6 is one of the most extensively studied drug-metabolizing enzymes and pharmacogenes. CYP2D6 alleles confer no, decreased, normal, or increased activity and cause a wide range of activity among individuals and between populations. However, there is no standard approach to translate diplotypes into predicted phenotype. METHODS: We exploited CYP2D6 allele-frequency data that have been compiled for Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (>60,000 subjects, 173 reports) in order to estimate genotype-predicted phenotype status across major world populations based on activity score (AS) assignments. RESULTS: Allele frequencies vary considerably across the major ethnic groups predicting poor metabolizer status (AS = 0) between 0.4 and 5.4% across world populations. The prevalence of genotypic intermediate (AS = 0.5) and normal (AS = 1, 1.5, or 2) metabolizers ranges between 0.4 and 11% and between 67 and 90%, respectively. Finally, 1 to 21% of subjects (AS >2) are predicted to have ultrarapid metabolizer status. CONCLUSIONS: This comprehensive study summarizes allele frequencies, diplotypes, and predicted phenotype across major populations, providing a rich data resource for clinicians and researchers. Challenges of phenotype prediction from genotype data are highlighted and discussed.Genet Med 19 1, 69-76. PMID- 27388692 TI - Cerebellar physiology: links between microcircuitry properties and sensorimotor functions. AB - Existing knowledge of the cerebellar microcircuitry structure and physiology allows a rather detailed description of what it in itself can and cannot do. Combined with a known mapping of different cerebellar regions to afferent systems and motor output target structures, there are several constraints that can be used to describe how specific components of the cerebellar microcircuitry may work during sensorimotor control. In fact, as described in this review, the major factor that hampers further progress in understanding cerebellar function is the limited insights into the circuitry-level function of the targeted motor output systems and the nature of the information in the mossy fiber afferents. The cerebellar circuitry in itself is here summarized as a gigantic associative memory element, primarily consisting of the parallel fiber synapses, whereas most other circuitry components, including the climbing fiber system, primarily has the role of maintaining activity balance in the intracerebellar and extracerebellar circuitry. The review explores the consistency of this novel interpretational framework with multiple diverse observations at the synaptic and microcircuitry level within the cerebellum. PMID- 27388695 TI - A model for ovarian cancer progression based on inherent resistance. AB - OBJECTIVE: Women with ovarian cancer are treated with debulking surgery and chemotherapy. The bulk of ovarian cancer cells are resistant to chemotherapy prior to the death of the patient. It is not clear if chemoresistance is an acquired property of cells under the selective pressure of chemotherapy or if it is an innate property of a small proportion of cancer cells from the outset. METHODS: We developed a mathematical model to describe ovarian cancer progression based on the assumption that a small proportion of ovarian cancer cells are chemoresistant from the beginning (0.1%) and that there is no acquired resistance. The doubling time was fixed at two months for sensitive cells and four months for resistant cells. RESULTS: The proportion of chemoresistant cells increased over time and at the time of death, 90% of cells were resistant. The typical patient responded to the first three rounds of chemotherapy but was non responsive thereafter. When we assume that the doubling times of the cancer cells is not fixed, but varies according to a normal distribution, the mean doubling time of the cells diminishes with time from diagnosis and death ensues shortly after chemoresistance is observed. CONCLUSIONS: We show that a model of inherent resistance in ovarian cancer is able to recapitulate the clinical history of a typical patient with ovarian cancer and that it is not necessary to invoke acquired resistance. This observation has potential clinical implications about how to approach new therapies. PMID- 27388694 TI - Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation. AB - PURPOSE: The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the beta-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation. In this study, we describe the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG). METHODS: Prospective natural history protocol. RESULTS: In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure. Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination. We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features. CONCLUSION: Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168. PMID- 27388696 TI - Case-control study of cervical cancer and gynecologic screening: A SEER-Medicare analysis. AB - OBJECTIVE: To determine the association between Pap smear and pelvic examination screenings and the development of invasive cervical cancer in a Medicare population using a matched case-control design. METHODS: Matched case-control data sets were constructed from the SEER-Medicare database that links the Surveillance Epidemiology End Results (SEER) cancer registry data and Medicare enrollment and claims data of subjects who received care between the years 1991 and 1999 aged 65years or older. The study identified 1267 cervical cancer cases. Controls (N=10.137) were matched to cases representing up to eight matched controls (on age and registry geographic location) for a single case. The association between gynecologic screenings and the development of invasive cervical cancer was ascertained using conditional logistic regression analysis. RESULTS: Having had a Pap smear during the PIDP (pre-invasive detectable phase - 2 to 7years prior to diagnosis) was significantly negatively associated with the development of invasive cervical cancer (OR=0.64, 95% CI=0.53-0.78) which was reduced after taking into account the estimated prevalence of hysterectomy among controls (OR=0.38, 95% CI=0.32-0.46). The negative association between Pap smear screenings and cervical cancer was strongest for squamous tumors (OR=0.48, 95% CI=0.37-0.61). Restricting the subjects to those 72 and over did not affect risk. CONCLUSIONS: There is a reduction in risk for invasive cervical cancer when women over age 65 are screened. This suggests that cervical cancer screening in the aged population may be beneficial. PMID- 27388697 TI - Preoperative hyponatremia in women with ovarian cancer: An additional cause for concern? AB - OBJECTIVE: To determine if preoperative hyponatremia in women with ovarian, fallopian tube (FT), and primary peritoneal cancers (PPC) is associated with postoperative complications. METHODS: We performed a retrospective population based cohort study of women with a postoperative diagnosis of ovarian, FT, or PPC who had a cytoreductive procedure in the National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2013. The primary exposure, preoperative sodium, was classified as normal (135mEq/L-142mEq/L) or hyponatremic (<=134mEq/L). Where appropriate, preoperative characteristics were compared with Chi-squared or Fisher's exact tests. Multivariate logistic regression was used to determine adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: 4009 subjects met inclusion criteria. Thirty day mortality was higher in the hyponatremic group compared to the normal serum sodium group (3.56% vs 1.18%). When patients of any age were noted to have at least two pertinent preoperative lab abnormalities, including hyponatremia, there was an increased risk of postoperative complications for patients over the age of 65 (Table 3). After adjusting for serum albumin and other confounders, preoperative hyponatremia was associated with an increased risk of hospital stay of >14days (aOR 1.69; 95% CI 1.11-2.57) and 30day postoperative mortality (aOR 2.37; 95% CI 1.13-4.98). CONCLUSIONS: Hyponatremia is associated with postoperative 30day mortality and morbidity in women with ovarian, FT, and PPC. Serum sodium in conjunction with other markers may have the potential to identify candidates for neoadjuvant chemotherapy. Additional work is needed to determine if correction of hyponatremia in the preoperative period alters outcomes. PMID- 27388698 TI - Seroprevalence of Rift Valley fever virus in sheep and goats in Zambezia, Mozambique. AB - BACKGROUND: The Rift Valley fever virus (RVFV) is a vector-borne virus that causes disease in ruminants, but it can also infect humans. In humans, the infection can be asymptomatic but can also lead to illness, ranging from a mild disease with fever, headache and muscle pain to a severe disease with encephalitis and haemorrhagic fever. In rare cases, death can occur. In infected animals, influenza-like symptoms can occur, and abortion and mortality in young animals are indicative of RVFV infection. Since the initial outbreak in Kenya in the 1930s, the virus has become endemic to most of sub-Saharan Africa. In 2000, the virus appeared in Yemen and Saudi Arabia; this was the first outbreak of RVF outside of Africa. Rift Valley fever epidemics are often connected to heavy rainfall, leading to an increased vector population and spread of the virus to animals and/or humans. However, the virus needs to be maintained during the inter epidemic periods. In this study, we investigated the circulation of RVFV in small ruminants (goats and sheep) in Zambezia, Mozambique, an area with a close vector/wildlife/livestock/human interface. MATERIALS AND METHODS: Between September and October 2013, 181 sheep and 187 goat blood samples were collected from eight localities in the central region of Zambezia, Mozambique. The samples were analysed for the presence of antibodies against RVFV using a commercial competitive ELISA. RESULTS AND DISCUSSION: The overall seroprevalence was higher in sheep (44.2%) than goats (25.1%); however, there was a high variation in seroprevalence between different localities. The data indicate an increased seroprevalence for sheep compared to 2010, when a similar study was conducted in this region and in overlapping villages. No noticeable health problems in the herds were reported. CONCLUSIONS: This study shows an inter-epidemic circulation of RVFV in small ruminants in Zambezia, Mozambique. Neither outbreaks of RVF nor typical clinical signs of RVFV have been reported in the investigated herds, indicating subclinical infection. PMID- 27388700 TI - Wildlife cancer: Cancer mussels in. PMID- 27388699 TI - Biomarker development in the precision medicine era: lung cancer as a case study. AB - Precision medicine relies on validated biomarkers with which to better classify patients by their probable disease risk, prognosis and/or response to treatment. Although affordable 'omics'-based technology has enabled faster identification of putative biomarkers, the validation of biomarkers is still stymied by low statistical power and poor reproducibility of results. This Review summarizes the successes and challenges of using different types of molecule as biomarkers, using lung cancer as a key illustrative example. Efforts at the national level of several countries to tie molecular measurement of samples to patient data via electronic medical records are the future of precision medicine research. PMID- 27388703 TI - Raman spectroscopy of transition metal dichalcogenides. AB - Raman spectroscopy of transition metal dichalcogenides (TMDs) is reviewed based on our recent theoretical and experimental works. First, we discuss the semi classical and quantum mechanical description for the polarization dependence of Raman spectra of TMDs in which the optical dipole transition matrix elements as a function of laser excitation energy are important for understanding the polarization dependence of the Raman intensity and Raman tensor. Overviewing the symmetry of TMDs, we discuss the dependence of the Raman spectra of TMDs on layer thickness, polarization, laser energy and the structural phase. Furthermore, we discuss the Raman spectra of twisted bilayer and heterostructures of TMDs. Finally, we give our perspectives on the Raman spectroscopy of TMDs. PMID- 27388701 TI - Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age Related Osteoarthritis. AB - Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mechanisms through which physiologic or pathologic mechanical signals are transduced into a cellular response are not well understood. Defining the role of mechanosensory pathways in cartilage during OA pathogenesis may yield novel strategies or targets for the treatment of OA. The transient receptor potential vanilloid 4 (TRPV4) ion channel transduces mechanical loading of articular cartilage via the generation of intracellular calcium ion transients. Using tissue-specific, inducible Trpv4 gene-targeted mice, we demonstrate that loss of TRPV4-mediated cartilage mechanotransduction in adulthood reduces the severity of aging-associated OA. However, loss of chondrocyte TRPV4 did not prevent OA development following destabilization of the medial meniscus (DMM). These results highlight potentially distinct roles of TRPV4-mediated cartilage mechanotransduction in age-related and post-traumatic OA, and point to a novel disease-modifying strategy to therapeutically target the TRPV4-mediated mechanotransduction pathway for the treatment of aging-associated OA. PMID- 27388704 TI - Oxidative Unzipping and Transformation of High Aspect Ratio Boron Nitride Nanotubes into "White Graphene Oxide" Platelets. AB - Morphological and chemical transformations in boron nitride nanotubes under high temperature atmospheric conditions is probed in this study. We report atmospheric oxygen induced cleavage of boron nitride nanotubes at temperatures exceeding 750 degrees C for the first time. Unzipping is then followed by coalescence of these densely clustered multiple uncurled ribbons to form stacks of 2D sheets. FTIR and EDS analysis suggest these 2D platelets to be Boron Nitride Oxide platelets, with analogous structure to Graphene Oxide, and therefore we term them as "White Graphene Oxide" (WGO). However, not all BNNTs deteriorate even at temperatures as high as 1000 degrees C. This leads to the formation of a hybrid nanomaterial system comprising of 1D BN nanotubes and 2D BN oxide platelets, potentially having advanced high temperature sensing, radiation shielding, mechanical strengthening, electron emission and thermal management applications due to synergistic improvement of multi-plane transport and mechanical properties. This is the first report on transformation of BNNT bundles to a continuous array of White Graphene Oxide nanoplatelet stacks. PMID- 27388702 TI - Polymorphism analysis of prion protein gene in 11 Pakistani goat breeds. AB - The association between caprine PrP gene polymorphisms and its susceptibility to scrapie has been investigated in current years. As the ORF of the PrP gene is extremely erratic in different breeds of goats, we studied the PrP gene polymorphisms in 80 goats which belong to 11 Pakistani indigenous goat breeds from all provinces of Pakistan. A total of 6 distinct polymorphic sites (one novel) with amino acid substitutions were identified in the PrP gene which includes 126 (A -> G), 304 (G -> T), 379 (A -> G), 414 (C -> T), 428 (A -> G) and 718 (C -> T). The locus c.428 was found highly polymorphic in all breeds as compare to other loci. On the basis of these PrP variants NJ phylogenetic tree was constructed through MEGA6.1 which showed that all goat breeds along with domestic sheep and Mauflon sheep appeared as in one clade and sharing its most recent common ancestors (MRCA) with deer species while Protein analysis has shown that these polymorphisms can lead to varied primary, secondary and tertiary structure of protein. Based on these polymorphic variants, genetic distance, multidimensional scaling plot and principal component analyses revealed the clear picture regarding greater number of substitutions in cattle PrP regions as compared to the small ruminant species. In particular these findings may pinpoint the fundamental control over the scrapie in Capra hircus on genetic basis. PMID- 27388705 TI - Extra luminal migration of ingested fish bone to the spleen as an unusual cause of splenic rupture: Case report and literature review. AB - INTRODUCTION: The ingestion of foreign bodies (FB) is a common problem worldwide and affects all ages; it is, however, particularly important in the pediatric population and in mentally impaired adults. The typical outcome of FB ingestion is good, since the majority of ingested material is passed spontaneously through the gastrointestinal tract. Serious complications can occur, however, including bowel perforation or obstruction and gastrointestinal bleeding, amongst others. Extraluminal migration of ingested foreign bodies is very rare and reported cases so far have shown, more commonly, migration to neck structures, with very few reported cases of migration to the abdomen. To date, there is no reported case of extraluminal migration of ingested FB to the spleen. CASE PRESENTATION: A 59-year old man presented with acute abdominal pain and dyspnea. A CT scan revealed a FB within the spleen, with a ruptured capsule and perisplenic collection. Surgery was performed and a 3cm-long fishbone was extracted, with hemoperitoneum secondary to spleen rupture. The patient was discharged on the third postoperative day with good recovery and without any complications; pneumococcal polysaccharide vaccination was provided. CONCLUSION: FB ingestion is a relatively benign condition; however, some serious complications can arise infrequently. The patient reported herein is the first in the literature to present a splenic rupture due to extra luminal migration of an ingested fish bone. PMID- 27388706 TI - Malignant peripheral nerve sheath tumor with extensive osteosarcomatous and chondrosarcomatous differentiation: A case report. AB - BACKGROUND: Malignant peripheral nerve sheath tumor is an uncommon tumor of the peripheral nerves. The commonest presenting symptom is soft tissue mass and pain with local neurological findings. Imaging modalities are unhelpful in making a reliable diagnosis. Treatment is radical resection with adequate clear resection margins. Radiotherapy improves the local control, but the prognosis remains poor especially in those with divergent differentiation. SUMMARY: A 23-year-old man with no history of neurofibromatosis presented with a swelling on the back which has been gradually increasing in size and causing him discomfort. The tumor was surgically excised and the histopathological examination revealed malignant peripheral nerve sheath tumor with extensive osseous and cartilaginous differentiation. He developed pulmonary metastases one year after the surgical resection. Pulmonary metastatectomy was therefore performed and the histopathology of the metastatectomy specimen revealed metastatic malignant peripheral nerve sheath tumor, but without any osseous or cartilaginous differentiation. He remained well with no recurrence or metastases at 9-month follow-up. CONCLUSION: Malignant peripheral nerve sheath tumor is a malignant tumor that behaves aggressively despite adequate radical resection. This case also illustrates extensive osseous and cartilaginous divergent differentiation of the primary tumor which was surprisingly absent in the metastatic lesions. This finding warrants further research. PMID- 27388707 TI - When a lymphatic malformation determines a bowel volvulus: Are clinical status and images always reliable? AB - INTRODUCTION: An acute abdomen in the form of small-bowel volvulus could be a presentation of a lymphatic malformation in childhood. CASE PRESENTATION: A 5year old male was admitted to our Institute for an acute abdomen. Clinical aspects and radiological images were not specific for a certain diagnosis. Laparotomy revealed a big soft mass, with a milky content, completely involving about 50cm of ileus with a partial volvulus of the intestinal loop. A complete mass excision and also a bowel involved resection were performed. After a histological examination, a lymphatic malformation was diagnosed. DISCUSSION: The diagnosis of a mesenteric lymphatic malformation could be intraoperative and a complete resection should be the treatment of choice. Sometimes it could be necessary to perform an involved bowel tract resection in the case of volvolus with ischemia. CONCLUSIONS: Paediatricians and surgeons should bare in mind that an intrabdominal lymphatic malformation may present as a nonspecific an acute abdomen caused by a bowel volvolus and diagnosis may not be so simple preoperatively. PMID- 27388708 TI - To Load or Not to Load? Aspirin Loading in Acute Ischemic Stroke: A Study of Clinical Outcomes. AB - BACKGROUND AND PURPOSE: Aspirin is known to reduce mortality and recurrent vascular events. However, there are no reports about the dose-response of loading aspirin in treating acute ischemic stroke. The objective of this study was to compare the effectiveness of different loading doses of aspirin in acute ischemic stroke presenting within 48 hours of symptom onset. METHODS: This was a retrospective, hospital-based cohort study. Patients were classified as high dose (160-325 mg) or low dose (<160 mg) based on the initial loading dose of aspirin at the emergency department. The primary outcome measure was a favorable modified Rankin Scale (mRS) score of 1 or lower on discharge. Secondary outcomes included in-hospital mortality, stroke progression during admission, and bleeding events. A propensity score with 1:3 matching was used to balance baseline characteristics, and stepwise multiple logistic regression was performed for variable adjustment. RESULTS: From a total of 7738 available patients, 3802 patients were included. Among them, 750 patients were in the high-dose group. Multiple logistic regression after matching revealed that the high-dose group was significantly associated with a favorable clinical outcome on discharge (odds ratio: 1.49, 95% confidence interval: 1.17-1.89, P <.01), but not mortality or stroke progression. The high-dose group also experienced more minor bleeding events. CONCLUSIONS: A higher loading dose of aspirin (160-325 mg) can be beneficial in treating acute ischemic stroke, although there is an increased risk of minor bleeding. PMID- 27388709 TI - Changes in Quadriceps Muscle Thickness, Disease Severity, Nutritional Status, and C-Reactive Protein after Acute Stroke. AB - BACKGROUND: Lower leg muscle wasting is common in stroke patients; however, patient characteristics in the acute phase are rarely studied. This study aimed to examine the relationship between changes in quadriceps muscle thickness and disease severity, nutritional status, and C-reactive protein (CRP) levels after acute stroke. METHODS: Thirty-one consecutive patients with acute intracerebral hemorrhage or ischemic stroke had quadriceps muscle thickness measured in the paretic and nonparetic limbs within 1 week after admission (first week) and 2 weeks after the first examination (last week) using ultrasonography. We also determined the relationship between the percentage change in muscle thickness and disease severity, nutritional status, and CRP levels on admission. RESULTS: There was a significant correlation between changes in muscle thickness for both paretic and nonparetic sides and National Institutes of Health Stroke Scale (NIHSS) scores (paretic limb: r = -.46, P = .01; nonparetic limb: r = -.54, P = .002, respectively); however, there was no significant correlation with nutritional status on admission. Quadriceps muscle thickness was reduced more in the CRP-positive (>=.3 mg/dL) patients than in the CRP-negative (<.3 mg/dL) patients in the nonparetic limb (positive: -21.4 +/- 12.1, negative: -11.4 +/- 16.4%; P = .039), but not in the paretic limb (positive: -23.4 +/- 9.0, negative: -19.1 +/- 15.7; P = .27). CONCLUSIONS: A high NIHSS score and a positive CRP on admission were both significantly correlated with decreased quadriceps muscle thickness after acute stroke. Nutritional status on admission was not correlated with changes in quadriceps muscle thickness for these patients. PMID- 27388710 TI - Access to free or low-cost tuberculosis treatment for migrants and refugees along the Thailand-Myanmar border in Tak province, Thailand. AB - BACKGROUND: In Tak province, Thailand migrants and refugees from Myanmar navigate a pluralistic healthcare system to seek Tuberculosis (TB) care from a variety of government and non-governmental providers. This multi-methods qualitative study examined access to TB, TB/HIV and multidrug-resistant tuberculosis (MDR-TB) treatment with an emphasis on barriers to care and enabling factors. METHODS: In the summer and fall of 2014, we conducted 12 key informant interviews with public health officials and TB treatment providers. We also conducted 11 focus group discussions with migrants and refugees who were receiving TB, TB/HIV and MDR-TB treatment in Tak province as well as non-TB patients. We analyzed these data through thematic analysis using both predetermined and emergent codes. As a second step in the qualitative analysis, we explored the barriers and enabling factors separately for migrants and refugees. RESULTS: We found that refugees face fewer barriers to accessing TB treatment than migrants. For both migrants and refugees, legal status plays an important intermediary role in influencing the population's ability to access care and eligibility for treatment. Our results suggest that there is a large geographical catchment area for migrants who seek TB treatment in Tak province that extends beyond provincial boundaries. Migrant participants described their ability to seek care as linked to the financial and non-financial resources required to travel and undergo treatment. Patients identified language of health services, availability of free or low cost services, and psychosocial support as important health system characteristics that affect accessibility. CONCLUSION: Access to TB treatment for migrants and refugees occurs at the interface of health system accessibility, population ability and legal status. In Tak province, migrant patients draw upon their social networks and financial resources to navigate a pathway to treatment. We revised a conceptual framework for access to healthcare to incorporate legal status and the cyclical pathways through which migrants access TB treatment in this region. We recommend that organizations continue to collaborate to provide supportive services that help migrants to access and continue TB treatment. PMID- 27388712 TI - Comparing Nalmefene and Naltrexone in Alcohol Dependence: Is there a Spin? PMID- 27388713 TI - Comparing Nalmefene and Naltrexone in Alcohol Dependence: Are there any Differences? Results from an Indirect Meta-analysis - Comment to Naudet. PMID- 27388711 TI - Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un differentiated cancer cells in a mouse xenograft model. AB - BACKGROUND: We previously demonstrated that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a demethylation process and p53 upregulation in vivo. Additionally, we have reported the non-tumorigenic effect of miR-520d-5p on normal human cells, including fibroblasts. METHODS: We used atelocollagen-conjugated miR-520d-5p (520d/atelocollagen) to confirm the possibility of a therapeutic effect on cancer cells. We traced the size and signal intensity of GFP-expressing tumors in mice each week, beginning 4 weeks after subcutaneous inoculation. RESULTS: 520d/atelocollagen treatment suppressed tumor growth by greater than 80 % each week relative to controls and resulted in an approximately 30 % disappearance of tumors. In mice whose tumors disappeared, the existence of human genomic material at the injection site was examined by quantitative Alu-PCR, and we confirmed the co-existence of both species-derived cells. In every site where a tumor disappeared in immunodeficient mice, GFP protein was expressed in the connective tissues, and approximately 0.1 % of the extracted DNA contained human genomic material. We could not identify any adverse effects in vivo. CONCLUSIONS: This is the first report to confirm an inhibitory effect of 520d/atelocollagen on cancer cells in vivo. The development of optimized modifications of this carrier is expected to enhance the efficiency of entry into tumor cells and the induction of its inhibitory effect. PMID- 27388714 TI - Neuroleptics Affect Kisspeptin mRNA Expression in the Male Rat Hypothalamus and Hippocampus. AB - Introduction: Kisspeptin has a multidirectional neuroendocrinal activity. It is especially considered to be a central regulator of reproductive function. Numerous data proved that neuroleptic administration may affect the peptidergic signaling in the various brain structures. However, there is no information concerning the relationship between treatment with neuroleptics and brain kisspeptin mRNA expression. Methods: We assessed the kisspeptin mRNA level in the hypothalamus and hippocampus of rats shortly and chronically (28 days) treated with haloperidol, chlorpromazine, and olanzapine using a quantitative Real-Time PCR method. Results: We have shown that all studied neuroleptics injected chronically have the ability to downregulate the kisspeptin mRNA expression in the hypothalamus, which may suggest the presence of an alternative mechanism for their orexigenic side effects. Long-term treatment with chlorpromazine increased the level of kisspeptin mRNA expression in the hippocampus. Discussion: Our results shed a new light on the pharmacology of antipsychotics and may contribute to a better understanding of alternative mechanisms responsible for their action. The study also highlights a complex nature of potential connections between dopamine transmission and brain kisspeptin pathways. PMID- 27388715 TI - The medial and lateral epicondyle as a reliable landmark for intra-operative joint line determination in revision knee arthroplasty. AB - OBJECTIVES: The purpose of this study was to develop an accurate, reliable and easily applicable method for determining the anatomical location of the joint line during revision knee arthroplasty. METHODS: The transepicondylar width (TEW), the perpendicular distance between the medial and lateral epicondyles and the distal articular surfaces (DMAD, DLAD) and the distance between the medial and lateral epicondyles and the posterior articular surfaces (PMAD, DLAD) were measured in 40 knees from 20 formalin-fixed adult cadavers (11 male and nine female; mean age at death 56.9 years, sd 9.4; 34 to 69). The ratios of the DMAD, PMAD, DLAD and PLAD to TEW were calculated. RESULTS: The mean TEW, DMAD, PMAD, DLAD and PLAD were 82.76 mm (standard deviation (sd) 7.74), 28.95 mm (sd 3.3), 28.57 mm (sd 3), 23.97 mm (sd 3.27) and 24.42 mm (sd 3.14), respectively. The ratios between the TEW and the articular distances (DMAD/TEW, DLAD/TEW, PMAD/TEW and PLAD/TEW) were calculated and their means were 0.35 (sd 0.02), 0.34 (sd 0.02), 0.28 (sd 0.03) and 0.29 (sd 0.03), respectively. CONCLUSION: This method provides a simple, reproducible and reliable technique enabling accurate anatomical joint line restoration during revision total knee arthroplasty.Cite this article: B. Ozkurt, T. Sen, D. Cankaya, S. Kendir, K. Basarir, Y. Tabak. The medial and lateral epicondyle as a reliable landmark for intra-operative joint line determination in revision knee arthroplasty. Bone Joint Res 2016;5:280-286. DOI: 10.1302/2046-3758.57.BJR-2016-0002.R1. PMID- 27388716 TI - High-sensitivity cardiac troponin assays and unstable angina. AB - The term unstable angina has been conventionally applied to patients with myocardial ischemia without myocardial necrosis. However, while the clinical context has remained constant over time, the biomarkers of myocardial injury and acute myocardial infarction have evolved. High-sensitivity cardiac troponin assays have several key analytical differences from prior cardiac troponin assay generations, which may alter the diagnosis and frequency of unstable angina, as well as affect our understanding of previously developed risk stratification strategies. This document reviews the current challenges in regards to unstable angina when using high-sensitivity cardiac troponin I and T assays. PMID- 27388717 TI - IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo. AB - IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2) associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL 33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo. PMID- 27388718 TI - Improved Pulsed Laser Operation with Engineered Nanomaterials. AB - The power efficiency of a diode-pumped solid state laser was improved by encasing the Nd:YAG lasing medium with gold nanorod-doped epoxy. Gold nanorods were synthesized with a specific aspect ratio tuned to absorb at the Nd:YAG lasing wavelength of 1064 nm. The surfactant-stabilized nanorods in aqueous solution were then treated with a sequential, two-step functionalization in order to improve nanorod solubility in organic solvents. This process required treating the gold nanorods with a thiol-containing polyethylene glycol (PEG) polymer followed by replacing the PEG-SH polymer with a multidentate thiol containing block copolymer synthesized using RAFT synthesis. With a multidentate polymer, the nanorods were soluble in traditional epoxies that could be used to coat the outside of Nd:YAG rods. By absorbing excess lateral 1064 nm emission, the gold nanorod coating attenuates amplified spontaneous emission (ASE), a parasitic, incoherent process that limits power produced by Q-switch laser designs. Laser power increased by nearly 2-fold with addition of the 1064 nm absorbing gold nanorod coating. Gold nanorod epoxy coatings stand out as attractive materials for attenuating ASE by avoiding the fabrication difficulties of samarium oxide ceramics and the photostability limitations of organic dyes. PMID- 27388719 TI - AU-1 from Agavaceae plants causes transient increase in p21/Cip1 expression in renal adenocarcinoma ACHN cells in an miR-34-dependent manner. AB - Here, we show that AU-1, spirostanol saponin isolated from Agavaceae plants, causes a transient increase in cyclin-dependent kinase inhibitor (CDKI) p21/Cip1 through the upregulation of miRNAs, miR-34 and miR-21. AU-1 stimulated p21/Cip1 expression without exerting cytotoxicity against different types of carcinoma cell lines. In renal adenocarcinoma ACHN cells, AU-1 transiently elevated the expression level of p21/Cip1 protein without marked increases in p21/Cip1 mRNA levels. Rapid and transient increases in miR-34 and miR-21, both of which are known to upregulate p21/Cip1, were observed in AU-1-treated cells. Inhibitor for miR-34 and for miR-21 significantly blocked the AU-1-caused increase in p21/Cip1, indicating that elevation of p21/Cip1 protein by AU-1 is dependent on these microRNAs. We further clarified that NAD-dependent deacetylase SIRT1, a direct target of miR-34, is decreased by the treatment with AU-1. Furthermore, we found that SIRT1-knockdown increases p21/Cip1 protein levels in an miR-21-dependent manner. On the other hand, ectopic expression of p21/Cip1 resulted in the lowered expression of miR-34 and miR-21, suggesting that reciprocal regulation exists between p21/Cip1 and these miRNAs. We propose that the following feedback network composed of miR-34/SIRT1/miR-21/p21 is triggered by the treatment with AU-1: in cells treated with AU-1, transient elevation of miR-34 leads to the downregulation of SIRT1, thereby miR-21 is freed from SIRT1-dependent suppression. Then, elevated miR-21 upregulates p21/Cip1 protein, followed by the suppression of miR-34 expression. PMID- 27388720 TI - Nonsurgical Management of Adolescent Idiopathic Scoliosis. AB - Pediatric patient visits for spinal deformity are common. Most of these visits are for nonsurgical management of scoliosis, with approximately 600,000 visits for adolescent idiopathic scoliosis (AIS) annually. Appropriate management of scoliotic curves that do not meet surgical indication parameters is essential. Renewed enthusiasm for nonsurgical management of AIS (eg, bracing, physical therapy) exists in part because of the results of the Bracing in Adolescent Idiopathic Scoliosis Trial, which is the only randomized controlled trial available on the use of bracing for AIS. Bracing is appropriate for idiopathic curves between 20 degrees and 40 degrees , with successful control of these curves reported in >70% of patients. Patient adherence to the prescribed duration of wear is essential to maximize the effectiveness of the brace. The choice of brace type must be individualized according to the deformity and the patient's personality as well as the practice setting and brace availability. PMID- 27388721 TI - AAOS Appropriate Use Criteria: Treatment of Anterior Cruciate Ligament Injuries. PMID- 27388722 TI - Ab initio studies on the spin-forbidden cooling transitions of the LiRb molecule. AB - The spin-forbidden cooling of the LiRb molecule is investigated based on ab initio quantum chemistry calculations. The multireference configuration interaction method is used to generate the potential energy curves (PECs) of the ground state X(1)Sigma(+) and the low-lying excited states a(3)Sigma(+), B(1)Pi, and b(3)Pi. The spin-orbit coupling effects for the PECs and the transition dipole moments (TDMs) between the X(1)Sigma(+), b(3)Pi and a(3)Sigma(+) states are also calculated. The analytical functions for the PECs are deduced. The rovibrational energy levels, the spectroscopic parameters and the Franck-Condon factors (FCF) are determined by solving the Schrodinger equation of nuclear movement with the obtained analytical functions. The b(3)Pi0 <-> X(1)Sigma(+) and b(3)Pi1 <-> X(1)Sigma(+) transitions have highly diagonal distributed FCFs and non-zero TDMs, demonstrating that the LiRb molecule could be a very promising candidate for laser cooling. Therefore, a three-cycle laser cooling scheme for the molecule has been proposed based on these two spin-forbidden transitions. Using the radiative lifetime and linewidth calculated from the obtained TDM functions, we present further analysis of the cooling of LiRb and the corresponding KRb molecule. The transition b(3)Pi0 <-> X(1)Sigma(+) is found to be a practical transition to cool the LiRb molecule, and a sub-microkelvin cool temperature could be reached for the KRb molecule using a similar laser cooling scheme. PMID- 27388723 TI - Dysgonomonas capnocytophagoides bacteremia due to liver abscesses after radiofrequency ablation in a patient with hepatocellular carcinoma. PMID- 27388724 TI - Perceived inadequate care and excessive overprotection during childhood are associated with greater risk of sleep disturbance in adulthood: the Hisayama Study. AB - BACKGROUND: Sleep disturbance and poor sleep quality are major health problems worldwide. One potential risk factor for the development and maintenance of sleep disturbance is the parenting style experienced during childhood. However, its role in sleep disturbance in adulthood has not yet been estimated. This Japanese population study was done to clarify the relation between the parenting styles "care" and "overprotection" during childhood and sleep disturbance in adulthood. METHODS: A total of 702 community-dwelling Japanese residents aged >= 40 years were assessed in 2011 for their perceptions of the parenting style of their parents by use of the Parental Bonding Instrument (PBI) and for sleep disturbance by use of the Pittsburgh Sleep Quality Index (PSQI). The odds ratio (OR) for sleep disturbance (a global PSQI score > 5) was calculated using a logistic regression model. RESULTS: The prevalence of sleep disturbance was 29 %. After adjusting for sociodemographic, lifestyle, and physical factors in a comparison with the optimal parenting styles (high care and low overprotection), the ORs for sleep disturbance by men were significantly higher for low paternal care, by 2.49 times (95 % confidence interval [CI]: 1.21-5.09), and for high overprotection, by 2.40 times (95 % CI: 1.19-4.85), while the ORs were not significant for low maternal care and high overprotection. For women the only significant factor was high maternal overprotection, by 1.62 times (95 % CI: 1.05-2.52), while the ORs were not significant for low maternal care, low paternal care and high paternal overprotection. The association remained significant for high paternal overprotection for men after additionally controlling for depression. CONCLUSIONS: This study suggests that parenting style, especially inadequate care and excessive overprotection during childhood, is related to sleep disturbance in adulthood and that the association is much more significant for parents of the same sex as the child. PMID- 27388725 TI - LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION. AB - PURPOSE: To characterize longitudinal structural changes in early stages of late onset retinal degeneration to investigate pathogenic mechanisms. METHODS: Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. RESULTS: Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. CONCLUSION: Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations. PMID- 27388726 TI - Anti-Vascular Endothelial Growth Factor Therapy in Pregnancy: What We Know, What We Don't Know, and What We Don't Know We Don't Know. PMID- 27388727 TI - Correspondence. PMID- 27388728 TI - Correspondence. PMID- 27388729 TI - Correspondence. PMID- 27388730 TI - Correspondence. PMID- 27388731 TI - In Vivo Hemodynamic Changes of Vortex Vein Varix on Real-Time Video Angiography. PMID- 27388732 TI - Correspondence. PMID- 27388733 TI - Combined 27-Gauge Pars Plana Vitrectomy and Scleral Fixation of an Akreos AO60 Intraocular Lens Using Gore-Tex Suture. PMID- 27388734 TI - Twenty-Seven-Gauge Vitrectomy-Assisted Four-Point Scleral Fixation of Intraocular Lens in the Absence of Capsular Support. PMID- 27388735 TI - Correspondence. PMID- 27388736 TI - The Demise of the Bull's Eye (Screening for Hydroxychloroquine Retinopathy). PMID- 27388737 TI - Correspondence. PMID- 27388738 TI - Reply. PMID- 27388739 TI - Reply. PMID- 27388740 TI - Reply. PMID- 27388741 TI - Reply. PMID- 27388742 TI - Reply. PMID- 27388743 TI - Reply. PMID- 27388744 TI - METAANALYSIS OF REAL-WORLD OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR THE TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: To report the efficacy and safety of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD) in real-world practice. METHODS: Metaanalysis of ~26,360 patients from 42 real-world observational studies reporting outcomes of intravitreal ranibizumab for nAMD published between 2007 and 2015. Baseline demographics, lesion type, and visual acuity (VA) were recorded. The weighted mean was calculated for change in VA and frequency of injections and visits during year 1, year 2, and >=3 years. Local and systemic adverse events were recorded. RESULTS: The mean change in VA for patients receiving a treat-and-extend regimen was +8.8 (95% confidence interval [CI]: 5.8 to 11.8), +6.7 (95% CI: 3.2 to 10.1), and +5.4 (95% CI: -4.1 to 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 1 year (n = 1,539), 2 years (n = 2,521), and >=3 years (n = 1,298), in comparison with +3.5 (95% CI: 2.0 to 5.0), +1.3 (95% CI: -1.6 to 4.2), and -1.9 (95% CI: -9.8 to 6.0) ETDRS letters for pro re nata at 1 year (n = 20,247), 2 years (n = 14,408), and >=3 years (n = 11,714). Treat-and-extend patients received on average more injections (6.9 vs. 4.7) but had fewer visits (7.6 vs. 9.2) in the first year. Baseline characteristics were similar between the regimens. The reported rate of endophthalmitis was 17 of 66,176 intravitreal injections (0.026%). CONCLUSION: Intravitreal ranibizumab for nAMD prevents severe visual loss in real-world practice. Patients can achieve visual gain from baseline, but the extent to which these are maintained in the long term may depend on the frequency of injections. PMID- 27388745 TI - A Program on Noninvasive Prenatal Diagnosis of alpha-Thalassemia in Mainland China: A Cost-Benefit Analysis. AB - The aim of the present study was to determine the cost effectiveness of a noninvasive prenatal diagnosis (PND) program for alpha-thalassemia (alpha-thal) using ultrasound scan. During a 5-year period, 1923 pregnancies at-risk for homozygous alpha(0)-thal were recruited into the noninvasive PND program. There were 1452 women who avoided invasive testing because of a normal ultrasound scan. The remaining 471 showed abnormal fetal ultrasonographic findings, and invasive testing was recommended. The overall cost of running the noninvasive PND program was US$213,383, while the cost of running the invasive program would have been US$554,810. The total savings were estimated at US$356,499 for women with an unaffected pregnancy with a net saving of US$246 per capita. This study demonstrated that it is cost effective to run a noninvasive PND program for alpha thal in an area where the disease is prevalent, and therefore effectively avoiding an invasive test in unaffected pregnancies. PMID- 27388746 TI - Sequential Regioselective C-H Functionalization of Thiophenes. AB - Herein, the sequential functionalization of 5-membered ring heterocycles is disclosed. By employing a pH sensitive directing group both directed and nondirected C-H activation pathways are available, providing access to 2,3,4- and 2,4,5-substituted thiophenes. The C-H arylation was performed in water, and using a surfactant greatly improved the yield and mass recovery. The use of a directing group with an on/off switch offers a potentially powerful means of generating diversity around medicinally relevant cores. PMID- 27388748 TI - Erratum to: Functional and evolutionary analyses of the miR156 and miR529 families in land plants. PMID- 27388747 TI - AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome. AB - Patients with basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, develop numerous basal cell carcinomas (BCC) due to germline mutations in the tumor suppressor PTCH1 and aberrant activation of Hedgehog (Hh) signaling. Therapies targeted at components of the Hh pathway, including the smoothened (SMO) inhibitor vismodegib, can ablate these tumors clinically, but tumors recur upon drug discontinuation. Using SKH1-Ptch1+/- as a model that closely mimics the spontaneous and accelerated growth pattern of BCCs in patients with BCNS, we show that AKT1, a serine/threonine protein kinase, is intrinsically activated in keratinocytes derived from the skin of newborn Ptch1+/- mice in the absence of carcinogenic stimuli. Introducing Akt1 haplodeficiency in Ptch1+/- mice (Akt1+/- Ptch1+/-) significantly abrogated BCC growth. Similarly, pharmacological inhibition of AKT with perifosine, an alkyl phospholipid AKT inhibitor, diminished the growth of spontaneous and UV-induced BCCs. Our data demonstrate an obligatory role for AKT1 in BCC growth, and targeting AKT may help reduce BCC tumor burden in BCNS patients. Cancer Prev Res; 9(10); 794-802. (c)2016 AACR. PMID- 27388749 TI - Ciliary Tissue Transplantation in the Rabbit Eye: Does the Localization of the Graft Affect Survival? AB - PURPOSE: To examine whether ciliary body transplantation is applicable, the graft is viable and the localization of the graft material affects graft survival. METHODS: Fifteen female New Zealand white rabbits were used. Three of them were used as donors, and a ciliary body graft was prepared from their enucleated eyes. There are two groups in the study according to the localization of the ciliary body graft in the anterior chamber. The graft was placed on the iris surface close to the pupil margin in group 1 and adjacent to the anterior chamber angle in group 2. Immunosuppressive treatment with cyclosporine A was given to the rabbits of both groups. The rabbits were sacrificed 1 month after ciliary transplantation, and their eyes were enucleated. After fixation, the graft and the surrounding tissue were examined by a pathologist macroscopically and microscopically with hematoxylin and eosin staining. RESULTS: One month after the transplantation, the treated eyes remained inflammation free, and the transplants seemed to be viable with evident vascularization and without hemorrhage and necrotic tissue. When we compared groups 1 and 2, there were no statistically significant differences in the histopathological findings between the groups. The grafts were found to be similar with normal ciliary tissue in regard to necrosis, hemorrhage and fibrosis, and there were no statistically significant differences in inflammatory cell density and in the epithelial cell morphology between the normal ciliary tissue and the grafts. CONCLUSION: Transplantation of allograft ciliary tissue either onto the surface of the iris or the anterior chamber angle under immunosuppression could be an effective treatment for chronic ocular hypotony. PMID- 27388750 TI - A cost effective analysis of fixed-dose combination of dutasteride and tamsulosin compared with dutasteride monotherapy for benign prostatic hyperplasia in Nigeria: a middle income perspective; using an interactive Markov model. AB - BACKGROUND: The number of Nigerian men presenting with benign prostatic hyperplasia is on the rise because of increase awareness about the ailment. With the renewed effort by the national health insurance scheme to cover the informal sector, it becomes imperative to determine the cost implication for managing Benign Prostatic Hyperplasia (BPH) and the cost effective drug combination to be adopted. The objective of this study is to estimate cost effective analysis (CEA) of fixed -dose combination of dutasteride and tamsulosin compared with dutasteride monotherapy from the health service provider perspective design. METHODS: An interactive Markov's model was used to generate incremental cost per QALY and incremental cost per life years gained. 2.9 million Men who were 50 years of age were fed into the model. The outcome measures included: costs of drug treatment, consultation, acute urinary retention (AUR), transurethral resection of prostate (TURP), hospitalisation post TURP, and quality adjusted life years (QALYs), incremental cost per life years gained, and incremental cost per QALY gained. RESULTS: Fixed-dose combination of dutasteride and tamsulosin (FDCT) produced an Incremental cost-effectiveness ratios of US$1481.92 per Quality adjusted for life-years saved. CONCLUSION: Universal FDCT provision for Nigeria has major economic implications. This study in the context of its limitations has demonstrated the cost effectiveness of FDCT for the long term treatment of patients with moderate to severe BPH from the perspective of a developing country. Currently, there are few studies available to give economic data evidence to policy makers in Nigeria which is applicable to developing countries with similar economies. As such, the findings in this study will be relevant to policy makers in these countries. PMID- 27388751 TI - Between a Rock and a Hard Place: Ethical and Professional Dilemmas in a Psychiatric Hospital Under Missile Attacks. AB - BACKGROUND: Israeli hospitals must continuously develop various mechanisms to protect both patients and staff against the physical threat of missile attacks during war situations. OBJECTIVES: To examine the difficulties and dilemmas with which the staff of a psychiatric hospital had to deal during missile attacks. DESIGN: A quality improvement project consisting of three stages (1) establishment of a steering committee; (2) execution of a staff nurses' focus group; and (3) categorization of issues raised and suggestions for care improvement in future emergencies. RESULTS: The project stressed the challenges of dealing with restrained patients during missile alarms, waking up patients or dealing with those who refuse to enter the protected area, mismatching of the security needs in protected areas, and institutionalized emotional support for staff members. CONCLUSION: Suitable policies for clinical and management behavior and for information transfer between management and wards are essential during a continuous emergency. PMID- 27388752 TI - Investigation of 2 Types of Self-administered Acupressure for Persistent Cancer Related Fatigue in Breast Cancer Survivors: A Randomized Clinical Trial. AB - Importance: Fatigue is a common and debilitating late-term effect of breast cancer that is associated with poor sleep and decreased quality of life, yet therapies remain limited. Acupressure has reduced fatigue in previous small studies, but rigorous clinical trials are needed. Objectives: To investigate if 6 weeks of 2 types of self-administered acupressure improved fatigue, sleep, and quality of life vs usual care in breast cancer survivors and to determine if changes were sustained during a 4-week washout period. Design, Setting, and Participants: Phase 3 randomized, single-blind, clinical trial conducted from March 1, 2011, through October 31, 2014. Women were recruited from the Michigan Tumor Registry. Interventions: Randomization (1:1:1) to 6 weeks of daily self administered relaxing acupressure, stimulating acupressure, or usual care. Main Outcomes and Measures: The primary outcome was change in the Brief Fatigue Inventory score from baseline to weeks 6 and 10. Secondary analyses were sleep (Pittsburgh Sleep Quality Index) and quality of life (Long-Term Quality of Life Instrument). Results: A total of 424 survivors of stages 0 to III breast cancer who had completed cancer treatments at least 12 months previously were screened, and 288 were randomized, with 270 receiving relaxing acupressure (n = 94), stimulating acupressure (n = 90), or usual care (n = 86). One woman withdrew owing to bruising at the acupoints. At week 6, the percentages of participants who achieved normal fatigue levels (Brief Fatigue Inventory score <4) were 66.2% (49 of 74) in relaxing acupressure, 60.9% (42 of 70) in stimulating acupressure, and 31.3% (26 of 84) in usual care. At week 10, a total of 56.3% (40 of 71) in relaxing acupressure, 60.9% (42 of 69) in stimulating acupressure, and 30.1% (25 of 83) in usual care continued to have normal fatigue. At neither time point were the 2 acupressure groups significantly different. Relaxing acupressure, but not stimulating acupressure, showed significant improvements in sleep quality compared with usual care at week 6, but not at week 10. Only relaxing acupressure significantly improved quality of life vs usual care at weeks 6 and 10. Conclusions and Relevance: Both acupressure arms significantly reduced persistent fatigue compared with usual care, but only relaxing acupressure had significant effects on sleep quality and quality of life. Relaxing acupressure offers a possible low-cost option for managing symptoms. Trial Registration: clinicaltrials.gov Identifier: NCT01281904. PMID- 27388753 TI - An evaluation of the usefulness of single pass albumin dialysis: key role of dialysate flow rate. PMID- 27388754 TI - Preclinical PET imaging of EGFR levels: pairing a targeting with a non-targeting Sel-tagged Affibody-based tracer to estimate the specific uptake. AB - BACKGROUND: Though overexpression of epidermal growth factor receptor (EGFR) in several forms of cancer is considered to be an important prognostic biomarker related to poor prognosis, clear correlations between biomarker assays and patient management have been difficult to establish. Here, we utilize a targeting directly followed by a non-targeting tracer-based positron emission tomography (PET) method to examine some of the aspects of determining specific EGFR binding in tumors. METHODS: The EGFR-binding Affibody molecule ZEGFR:2377 and its size matched non-binding control ZTaq:3638 were recombinantly fused with a C-terminal selenocysteine-containing Sel-tag (ZEGFR:2377-ST and ZTaq:3638-ST). The proteins were site-specifically labeled with DyLight488 for flow cytometry and ex vivo tissue analyses or with (11)C for in vivo PET studies. Kinetic scans with the (11)C-labeled proteins were performed in healthy mice and in mice bearing xenografts from human FaDu (squamous cell carcinoma) and A431 (epidermoid carcinoma) cell lines. Changes in tracer uptake in A431 xenografts over time were also monitored, followed by ex vivo proximity ligation assays (PLA) of EGFR expressions. RESULTS: Flow cytometry and ex vivo tissue analyses confirmed EGFR targeting by ZEGFR:2377-ST-DyLight488. [Methyl-(11)C]-labeled ZEGFR:2377-ST-CH3 and ZTaq:3638-ST-CH3 showed similar distributions in vivo, except for notably higher concentrations of the former in particularly the liver and the blood. [Methyl-(11)C]-ZEGFR:2377-ST-CH3 successfully visualized FaDu and A431 xenografts with moderate and high EGFR expression levels, respectively. However, in FaDu tumors, the non-specific uptake was large and sometimes equally large, illustrating the importance of proper controls. In the A431 group observed longitudinally, non-specific uptake remained at same level over the observation period. Specific uptake increased with tumor size, but changes varied widely over time in individual tumors. Total (membranous and cytoplasmic) EGFR in excised sections increased with tumor growth. There was no positive correlation between total EGFR and specific tracer uptake, which, since ZEGFR:2377 binds extracellularly and is slowly internalized, indicates a discordance between available membranous and total EGFR expression levels. CONCLUSIONS: Same-day in vivo dual tracer imaging enabled by the Sel-tag technology and (11)C-labeling provides a method to non-invasively monitor membrane-localized EGFR as well as factors affecting non-specific uptake of the PET ligand. PMID- 27388755 TI - Rapamycin/DiR loaded lipid-polyaniline nanoparticles for dual-modal imaging guided enhanced photothermal and antiangiogenic combination therapy. AB - Imaging-guided photothermal therapy (PTT) has promising application for treating tumors. Nevertheless, so far imaging-guided photothermal drug-delivery systems have been developed with limited success for tumor chemo-photothermal therapy. In this study, as the proof-of-concept, a stimuli-responsive tumor-targeting rapamycin/DiR loaded lipid-polyaniline nanoparticle (RDLPNP) for dual-modal imaging-guided enhanced PTT efficacy is reported for the first time. In this system, polyaniline (PANI) with pi-pi electronic conjugated system and effective photothermal efficiency is chosen as the appropriate model receptor of fluorescence resonance energy transfer (FRET), and loaded cyanine probe (e.g., 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide, DiR) acts as the donor of near-infrared fluorescence (NIRF). In addition, rapamycin (RAPA), which is used as the antiangiogenesis chemotherapeutic drug, can cutdown the tumor vessels and delay tumor growth obviously. After intravenous treatment of RDLPNPs into Hela tumor bearing mice, fluorescent (from DiR) and enhanced photoacoustic (from DLPNPs) signals were found in tumor site over time, which reached to peak at the 6h time point. After irradiating with an NIR laser, a good anti-tumor effect was observed owing to the enhanced photothermal and antiangiogenic effect of RDLPNPs. These results show that the multifunctional nanoparticle can be used as a promising imaging-guided photothermal drug delivery nanoplatform for cancer therapy. PMID- 27388756 TI - Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery. AB - Recombinant adenoviruses are used as vaccines, gene therapy vectors, and oncolytic viruses. However, the efficacy of such therapies is limited by pre existing neutralizing antibodies (NAbs), especially when the virus is administered systemically for a wider biodistribution or to reach multiple metastases. To protect adenovirus against NAbs we inserted an albumin-binding domain (ABD) in the main adenovirus capsid protein, the hexon. This domain binds serum albumin to shield the virus upon systemic administration. The ABD-modified adenoviruses bind human and mouse albumin and maintain the infectivity and replication capacity in presence of NAbs. In pre-immunized mice non-modified viruses are completely neutralized, whereas ABD-modified viruses preserve the ability to transduce target organs, induce oncolysis, or generate immune responses to expressed proteins. Our results indicate that albumin coating of the virus capsid represents an effective approach to evade pre-existing NAbs. This strategy has translational relevance in the use of adenovirus for gene therapy, cancer virotherapy, and vaccination. PMID- 27388757 TI - Correction: Integrated Taxonomy and DNA Barcoding of Alpine Midges (Diptera: Chironomidae). AB - [This corrects the article DOI: 10.1371/journal.pone.0149673.]. PMID- 27388758 TI - Green Stimulated Emission Boosted by Nonradiative Resonant Energy Transfer from Blue Quantum Dots. AB - Thanks to their tunability and versatility, the colloidal quantum dots (CQDs) made of II-VI semiconductor compound offer the potential to bridge the "green gap" in conventional semiconductors. However, when the CQDs are pumped to much higher initial excitonic states compared to their bandgap, multiexciton interaction is enhanced, leading to a much higher stimulated emission threshold. Here, to circumvent this drawback, for the first time, we show a fully colloidal gain in green enabled by a partially indirect pumping approach assisted by Forster resonance energy transfer process. By introducing the blue CQDs as exciton donors, the lasing threshold of the green CQDs, is reduced dramatically. The blue CQDs thus serve as an energy-transferring buffer medium to reduce excitation energy from pumping photons in a controlled way by injecting photoinduced excitons into green CQDs. Our newly developed colloidal pumping scheme could enable efficient CQD lasers of full visible colors by a single pump source and cascaded exciton transfer. This would potentially pave the way for an efficient multicolor laser for lighting and display applications. PMID- 27388759 TI - Are area-level effects just a proxy for school-level effects? Socioeconomic differences in alcohol consumption patterns among Swedish adolescents. AB - AIMS: Although recent studies have found significant variations in adolescent alcohol consumption across neighbourhoods, these investigations did not address another important context in adolescents' lives: schools. The purpose of this study was to not only simultaneously assess variations in adolescent alcohol use and binge drinking at the city district level and the school level but also analyse whether any such variations could be ascribed to the socioeconomic characteristics of the examined city districts, schools, and students. DESIGN: Cross-sectional study. SETTING: Stockholm, Sweden. PARTICIPANTS: Ninth-grade students (n=4349) attending schools (n=75) located in the city districts of the Stockholm municipality (n=14). MEASUREMENTS: Two measures based on information regarding alcohol consumption were constructed: alcohol use (no or yes) and binge drinking among alcohol users (ranging from "very seldom" to "a few times a week"). A wide range of socioeconomic characteristics was included at the city district, school, and student levels. Alcohol use was analysed using mixed effects logistic regression, whereas binge drinking among users was modelled using mixed-effects ordered logistic regression. FINDINGS: The results indicated that the school was more important than the city district in assessments of contextual variations in adolescent alcohol use in general and binge drinking in particular. Moreover, proportions of well-educated parents and high-performing students accounted for part of the school-level variation in alcohol use but not binge drinking. CONCLUSIONS: Failure to account for the school context may have caused past research to overestimate city district differences in alcohol consumption among adolescents. PMID- 27388760 TI - Genome Wide Identification and Functional Prediction of Long Non-Coding RNAs Responsive to Sclerotinia sclerotiorum Infection in Brassica napus. AB - Sclerotinia stem rot caused by Sclerotinia sclerotiorum affects canola production worldwide. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the regulation of gene expression in plants, in response to both abiotic and biotic stress. So far, identification of lncRNAs has been limited to a few model plant species, and their roles in mediating responses to biotic stresses are yet to be characterized in Brassica napus. The present study reports the identification of novel lncRNAs responsive to S. sclerotiorum infection in B. napus at two time points after infection (24 hpi and 48 hpi) using a stranded RNA-Sequencing technique and a detection pipeline for lncRNAs. Of the total 3,181 lncRNA candidates, 2,821 lncRNAs were intergenic, 111 were natural antisense transcripts, 76 possessed exonic overlap with the reference coding transcripts while the remaining 173 represented novel lnc- isoforms. Forty one lncRNAs were identified as the precursors for microRNAs (miRNAs) including miR156, miR169 and miR394, with significant roles in mediating plant responses to fungal phytopathogens. A total of 931 differentially expressed lncRNAs were identified in response to S. sclerotiorum infection and the expression of 12 such lncRNAs was further validated using qRT-PCR. B. napus antisense lncRNA, TCONS_00000966, having 90% overlap with a plant defensin gene, showed significant induction at both infection stages, suggesting its involvement in the transcriptional regulation of defense responsive genes under S. sclerotiorum infection. Additionally, nine lncRNAs showed overlap with cis-regulatory regions of differentially expressed genes of B. napus. Quantitative RT-PCR verification of a set of S. sclerotiorum responsive sense/antisense transcript pairs revealed contrasting expression patterns, supporting the hypothesis that steric clashes of transcriptional machinery may lead to inactivation of sense promoter. Our findings highlight the potential contributions of lncRNAs in regulating expression of plant genes that respond to biotic stress. PMID- 27388761 TI - Comparison of vascular access outcomes in patients with end-stage renal disease attributed to systemic lupus erythematosus vs. other causes: a retrospective cohort study. AB - BACKGROUND: U.S. hemodialysis patients with systemic lupus erythematosus (SLE) and end-stage renal disease (ESRD) are less likely than other ESRD patients to have a permanent vascular access (fistula or graft) in place at the dialysis start. We examined whether vascular access outcomes after dialysis start differed for SLE vs. other ESRD patients. METHODS: Among U.S. patients initiating hemodialysis in 2010 with only a catheter (n = 40,911; 384 with SLE) and using a permanent access on first dialysis (n = 13,073; 48 with SLE), we examined the association of SLE status with time to first placement of a permanent access (among catheter-only patients) and to loss of access patency (among patients using a permanent access on first dialysis), both censored 1 year after dialysis start, using multivariable Cox proportional hazards models. RESULTS: Among catheter-only patients, 46.1 % vs. 54.5 % of those with SLE-ESRD vs. other ESRD had a permanent access placed within 1 year after dialysis start. However, with adjustment, there was no association of 1-year placement with SLE status [HR = 1.00 (95 % CI, 0.86-1.17)]. SLE-ESRD vs. other ESRD patients starting dialysis with a permanent access were less likely to experience a 1-year loss of patency (43.8 % vs. 55.0 %), but this association was not statistically significant after adjustment [HR = 0.88 (0.57-1.37)]. CONCLUSION: These results suggest that SLE ESRD patients starting dialysis with a catheter are not more likely to have a permanent access placed in the first year of dialysis, despite an observed lack of association of SLE status with subsequent loss of vascular access patency among those starting dialysis with a permanent access. PMID- 27388764 TI - Idarucizumab: A Review as a Reversal Agent for Dabigatran. AB - Idarucizumab (Praxbind((r))), a humanized monoclonal antibody, is a specific reversal agent for the direct oral thrombin inhibitor dabigatran, available as its prodrug dabigatran etexilate (Pradaxa((r))). Idarucizumab is approved in several countries (including the USA, the EU, Canada and Australia) for use in adult patients on dabigatran when the reversal of its anticoagulant effects is required for emergency surgery/procedures or in the event of life-threatening or uncontrolled bleeding. In the ongoing pivotal RE-VERSE AD trial in these populations (n = 90), intravenous idarucizumab 5 g reversed dabigatran-induced prolongation of dilute thrombin time (dTT) and ecarin clotting time (ECT) within minutes. The median maximum percentage reversal was 100 % for both assays (primary endpoint). Idarucizumab normalized dTT and ECT in 88-98 % of patients who had elevated levels at baseline. After idarucizumab administration, bleeding stopped in 97 % of evaluable patients in the bleeding cohort within 24 h (median time to cessation of bleeding was 11.4 h), and the rate of normal intraoperative haemostasis was 92 % in the surgical cohort. Idarucizumab was generally well tolerated. In conclusion, idarucizumab is a unique and specific treatment option for the reversal of the anticoagulant effects of dabigatran in adult patients requiring emergency procedures or in the event of life-threatening or uncontrolled bleeding. PMID- 27388763 TI - Evaluation of the FACSPresto, a New Point of Care Device for the Enumeration of CD4% and Absolute CD4+ T Cell Counts in HIV Infection. AB - INTRODUCTION: Enumeration of CD4+ T lymphocytes is important for pre-ART disease staging and screening for opportunistic infections, however access to CD4 testing in resource limited settings is poor. Point of care (POC) technologies can facilitate improved access to CD4 testing. We evaluated the analytical performance of a novel POC device the FACSPresto compared to the FACSCalibur as a reference standard and to the PIMA, a POC device in widespread use in sub-Saharan Africa. METHOD: Specimens were obtained from 253 HIV infected adults. Venous blood samples were analyzed on the FACSPresto and the FACSCalibur, in a subset of 41 samples additional analysis was done on the PIMA. RESULTS: The absolute CD4 count results obtained on the FACSPresto were comparable to those on the FACSCalibur with low absolute (9.5cells/MUl) and relative bias (3.2%). Bias in CD4% values was also low (1.06%) with a relative bias of 4.9%. The sensitivity was lower at a CD4 count threshold of <=350cells/MUl compared with <=500cells/MUl (84.9% vs. 92.8%) resulting in a high upward misclassification rate at low CD4 counts. Specificity at thresholds of <=350cells/MUl and <=500cells/MUl were 96.6% and 96.8% respectively. The PIMA had a high absolute (-68.6cells/MUl) and relative bias (-10.5%) when compared with the FACSCalibur. At thresholds of <=350cells/MUl and <=500cells/MUl the sensitivity was 100% and 95.5% respectively; specificity was 85.7% and 84.2% respectively. The coefficients of repeatability were 4.13%, 5.29% and 9.8% respectively. DISCUSSION: The analytic performance of the FACSPresto against the reference standard was very good with better agreement and precision than the PIMA. The FACSPresto had comparable sensitivity at a threshold of 500 cells/MUl and better specificity than the PIMA. However the FACSPresto showed reduced sensitivity at low CD4 count thresholds. CONCLUSION: The FACSPresto can be reliably used as a POC device for enumerating absolute CD4 count and CD4% values. PMID- 27388762 TI - Role for the Rostromedial Tegmental Nucleus in Signaling the Aversive Properties of Alcohol. AB - BACKGROUND: While the rewarding effects of alcohol contribute significantly to its addictive potential, it is becoming increasingly appreciated that alcohol's aversive properties also play an important role in the propensity to drink. Despite this, the neurobiological mechanism for alcohol's aversive actions is not well understood. The rostromedial tegmental nucleus (RMTg) was recently characterized for its involvement in aversive signaling and has been shown to encode the aversive properties of cocaine, yet its involvement in alcohol's aversive actions have not been elucidated. METHODS: Adult male and female Long Evans rats underwent conditioned taste aversion (CTA) procedures where exposure to a novel saccharin solution was paired with intraperitoneal administration of saline, lithium chloride (LiCl), or ethanol (EtOH). Control rats underwent the same paradigm except that drug and saccharin exposure were explicitly unpaired. Saccharin consumption was measured on test day in the absence of drug administration, and rats were sacrificed 90 to 105 minutes following access to saccharin. Brains were subsequently harvested and processed for cFos immunohistochemistry. The number of cFos-labeled neurons was counted in the RMTg and the lateral habenula (LHb)-a region that sends prominent glutamatergic input to the RMTg. RESULTS: In rats that received paired drug and saccharin exposure, EtOH and LiCl induced significant CTA compared to saline to a similar degree in males and females. Both EtOH- and LiCl-induced CTA significantly enhanced cFos expression in the RMTg and LHb but not the hippocampus. Similar to behavioral measures, no significant effect of sex on CTA-induced cFos expression was observed. cFos expression in both the RMTg and LHb was significantly correlated with CTA magnitude with greater cFos being associated with more pronounced CTA. In addition, cFos expression in the RMTg was positively correlated with LHb cFos. CONCLUSIONS: These data suggest that the RMTg and LHb are involved in the expression of CTA and are consistent with previous work implicating the RMTg in aversive signaling. Furthermore, increased cFos expression in the RMTg following EtOH-induced CTA suggests that this region plays a role in signaling alcohol's aversive properties. PMID- 27388765 TI - miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells. AB - Glioblastoma is the most common and malignant brain tumor in humans. It is a heterogeneous tumor harboring glioblastoma stem cells (GSC) and other glioblastoma cells that survive and sustain tumor growth in a hypoxic environment via induction of autophagy and resistance to apoptosis. So, a therapeutic strategy to inhibit autophagy and promote apoptosis could greatly help control growth of glioblastoma. We created hypoxia using sodium sulfite (SS) for induction of substantiated autophagy in human GSC and glioblastoma SNB19 cells. Induction of autophagy was confirmed by acridine orange (AO) staining and significant increase in Beclin-1 in autophagic cells. microRNA database (miRDB) search suggested that miR-30e could suppress the autophagy marker Beclin-1 and also inhibit the caspase activation inhibitors (AVEN and BIRC6). Pro-apoptotic effect of proanthocyanidin (PAC) has not yet been explored in glioblastoma cells. Combination of 50 nM miR-30e and 150 MUM PAC acted synergistically for inhibition of viability in both cells. This combination therapy most effectively altered expression of molecules for inhibition of autophagy and induced extrinsic and intrinsic pathways of apoptosis through suppression of AVEN and BIRC6. Collectively, combination of miR-30e and PAC is a promising therapeutic strategy to inhibit autophagy and increase apoptosis in GSC and SNB19 cells. PMID- 27388767 TI - QuickStats: Percentage* of Medically Attended Injury Episodes(?) That Resulted in Time Lost from Work(S) or School,( ) by Number of Days Lost - National Health Interview Survey, United States, 2011-2014. AB - During 2011-2014, an average of 15.6 million medically attended injury episodes were reported annually among employed persons aged >=13 years. Nearly half of these injury episodes resulted in time lost from work: 7% for <1 day, 26% for 1-5 days, and 15% for >=6 days. An average of 9.4 million medically attended injury episodes were reported annually among persons aged >=5 years who attended school. More than one third of these injury episodes resulted in time lost from school: 9% for <1 day, 25% for 1-5 days, and 3% for >=6 days. PMID- 27388766 TI - An ethnographic study of strategies to support discussions with family members on end-of-life care for people with advanced dementia in nursing homes. AB - BACKGROUND: Most people with advanced dementia die in nursing homes where families may have to make decisions as death approaches. Discussions about end-of life care between families and nursing home staff are uncommon, despite a range of potential benefits. In this study we aimed to examine practices relating to end-of-life discussions with family members of people with advanced dementia residing in nursing homes and to explore strategies for improving practice. METHODS: An ethnographic study in two nursing homes where the Compassion Intervention was delivered. The Compassion Intervention provides a model of end of-life care engaging an Interdisciplinary Care Leader to promote integrated care, educate staff, support holistic assessments and discuss end of life with families. We used a framework approach, undertaking a thematic analysis of fieldwork notes and observations recorded in a reflective diary kept by the Interdisciplinary Care Leader, and data from in-depth interviews with 23 informants: family members, GPs, nursing home staff, and external healthcare professionals. RESULTS: Four major themes described strategies for improving practice: (i) educating families and staff about dementia progression and end-of life care; (ii) appreciating the greater value of in-depth end-of-life discussions compared with simple documentation of care preferences; (iii) providing time and space for sensitive discussions; and (iv) having an independent healthcare professional or team with responsibility for end-of-life discussions. CONCLUSIONS: The Interdisciplinary Care Leader role offers a promising method for supporting and improving end-of-life care discussions between families of people with advanced dementia and nursing home staff. These strategies warrant further evaluation in nursing home settings. PMID- 27388768 TI - New Found Hope for Antibiotic Discovery: Lipid II Inhibitors. AB - Research into antibacterial agents has recently gathered pace in light of the disturbing crisis of antimicrobial resistance. The development of modern tools offers the opportunity of reviving the fallen era of antibacterial discovery through uncovering novel lead compounds that target vital bacterial cell components, such as lipid II. This paper provides a summary of the role of lipid II as well as an overview and insight into the structural features of macrocyclic peptides that inhibit this bacterial cell wall component. The recent discovery of teixobactin, a new class of lipid II inhibitor has generated substantial research interests. As such, the significant progress that has been achieved towards its development as a promising antibacterial agent is discussed. PMID- 27388769 TI - The dynamics and mechanism of the antimicrobial activity of tea tree oil against bacteria and fungi. AB - Tea tree oil (TTO) is a yellow liquid extracted from Melaleuca alternifolia. Although the antimicrobial activity of TTO has been known for a long time, its specific antimicrobial effects and mechanism underlying these remain poorly characterized. The present study investigated the chemical composition of TTO and the dynamics and mechanism of its antimicrobial activities in two bacterial and two fungal strains. Gas chromatography-mass spectrometry analysis identified alkenes and alcohols as the main constituents of TTO. Terpinen-4-ol was the most abundant individual component, accounting for approximately 23 % of the TTO. Poisoned food technique assessment showed that the minimum inhibitory concentrations of TTO for bacterial strains (Escherichia coli and Staphylococcus aureus) and fungal strains (Candida albicans and Aspergillus niger) were 1.08 and 2.17 mg/mL, respectively. Antimicrobial dynamic curves showed that with increasing concentrations of TTO, the rate of cell killing and the duration of growth lag phase increased correspondingly. These data indicated that TTO produced concentration and time-dependent antimicrobial effects. The minimum bactericidal and fungicidal concentrations of TTO were 2.17, 4.34, and 4.34 against E. coli, S. aureus, and C. albicans, respectively. However, A. niger conidia were not completely eradicated, even after 3 days in the presence of 17.34 mg/mL TTO. Transmission electron microscopy images indicated that TTO penetrated the cell wall and cytoplasmic membrane of all the tested bacterial and fungal strains. TTO may also penetrate fungal organelle membrane. These findings indicated that TTO maybe exerts its antimicrobial effects by compromising the cell membrane, resulting in loss of the cytoplasm and organelle damage, which ultimate leads to cell death. PMID- 27388770 TI - Systematic protein-protein interaction and pathway analyses in the idiopathic inflammatory myopathies. AB - BACKGROUND: The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantibody targets has not been systematically explored. Protein-protein interaction and pathway analyses were conducted to identify pathways relevant to disease, using autoantibody targets and gene products of IIM-associated single nucleotide polymorphism (SNP) loci. METHODS: Protein-protein interactions were analysed using Disease Association Protein-Protein Link Evaluator (DAPPLE). Gene ontology and pathway analyses were conducted using Database for Annotation Visualisation and Integrated Discovery (DAVID) and Gene Relationships Across Implicated Loci (GRAIL). Analyses were undertaken including the targets of published autoantibodies, significant and suggestive SNPs from an IIM association study and autoantibody targets plus SNPs combined. RESULTS: The protein-protein interaction networks formed by autoantibody targets and associated SNPs showed significant direct and/or indirect connectivity (p < 0.05). Autoantibody targets plus associated SNPs combined resulted in more significant indirect and common interactor connectivity, suggesting autoantibody targets and proteins encoded by IIM-associated loci may be involved in common pathways. Tumour necrosis factor receptor-associated factor 6 (TRAF6) was identified as a hub protein, and UBE3B, HSPA1A, HSPA1B and PSMD3 also were identified as genes with significant connectivity. Pathway analysis identified that autoantibody targets and associated SNP regions are significantly interconnected (p < 0.01), and confirmed autoantibody target involvement in translational and post-translational processes. 'Ubiquitin' was the only keyword strongly linking significant genes across regions in all three GRAIL analyses of autoantibody targets and IIM associated SNPs. CONCLUSIONS: Autoantibody targets and IIM-associated loci show significant connectivity and inter-relatedness, and identify several key genes and pathways in IIM pathogenesis, possibly mediated via the ubiquitination pathway. PMID- 27388771 TI - Frequent detection of human polyomavirus 6 in keratoacanthomas. AB - BACKGROUND: The recent discovery of the Merkel cell polyomavirus and its consistent association with Merkel cell carcinoma has drawn attention to the numerous recently discovered polyomaviruses and their possible involvement in the etiopathogenesis of non-melanoma skin cancer (NMSC). Data on the recently discovered human polyomavirus 6 (HPyV6) and its role in NMSC are sparse and in part controversial. METHODS: In the present study we tested a large number (n = 299) of NMSC specimens for the presence of human polyomavirus 6 (HPyV6) by DNA PCR and HPyV6 fluorescence in situ hybridization (FISH). In detail, 59 keratoacanthomas (KA), 109 basal cell carcinomas (BCC), 86 squamous cell carcinomas (SCC) and 45 trichoblastomas (TB) were tested for the presence of HPyV6. RESULTS: HPyV6 DNA PCR and subsequent sequence analysis revealed that 25 KAs (42.3 %), 23 BCCs (21.1 %), 8 SCCs (9.3 %) and 10 TBs (22.2 %) were HPyV6 positive. The presence of HPyV6 DNA was visualized and validated on the single cell level within the histomorphological context by HPyV6 fluorescence in situ hybridization. CONCLUSIONS: The high frequency of HPyV6 DNA in 42.3 % of KA possibly points to a role for HPyV6 in the etiopathogenesis of KAs. Although the detection rate of HPyV6 DNA in BCCs and TBs is within the previously reported detection range in normal skin, it does not exclude a possible role for HPyV6 in the carcinogenesis in a significant subset of these skin tumors. PMID- 27388772 TI - Comparison of 3.0T MRI with 3D LAVA sequence and digital subtraction angiography for the assessment of accessory hepatic veins in Budd-Chiari syndrome. AB - PURPOSE: To compare 3D liver acceleration volume acquisition (LAVA) and digital subtraction angiography (DSA) for evaluating the presence of accessory hepatic veins (AHV) in Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: This was a retrospective study in 228 patients with BCS who underwent 3.0T magnetic resonance imaging (MRI) with the 3D LAVA sequence. Two reviewers noted AHV: openings located in the inferior vena cava (IVC), caliber, and the angle of entering into the IVC. MRI results were compared to DSA. Kappa statistics were calculated to quantify intrareader variability in detecting AHVs. RESULTS: On MRI, 63 patients demonstrated no AHV on LAVA images, 70 had one AHV, 62 had two AHVs, 26 patients had three AHVs, six patients had four AHVs, and one patient had five AHVs (P < 0.05 vs. DSA). The mean caliber of the AHVs was 8.3 +/- 4.0 mm compared to 9.9 +/- 3.2 for DSA (P < 0.001). Among the 301 AHVs, there were 140 with acute angles (46.5%), 71 with right angles (23.6%), and 90 with obtuse angles (29.8%). The prevalence of AHVs on DSA was 54.8% (125/228), while MRI demonstrated 301 AHVs in 165 patients, for a prevalence of 72.4% (165/228) compared to 54.8% for DSA (P = 0.001). The two methods were concordant in only 116/228 (50.9%) patients. The kappa coefficient demonstrated good intrareader consistency for all documented MRI findings of AHVs (kappa = 0.626 for caliber and kappa = 0.65 for angles). CONCLUSION: More AHVs were visible on MRI LAVA sequences than on conventional DSA. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:401-409. PMID- 27388773 TI - Neuronal TRPV1 activation regulates alveolar bone resorption by suppressing osteoclastogenesis via CGRP. AB - The transient receptor potential vanilloid 1 (TRPV1) channel is abundantly expressed in peripheral sensory neurons where it acts as an important polymodal cellular sensor for heat, acidic pH, capsaicin, and other noxious stimuli. The oral cavity is densely innervated by afferent sensory neurons and is a highly specialized organ that protects against infections as well as physical, chemical, and thermal stresses in its capacity as the first part of the digestive system. While the function of TRPV1 in sensory neurons has been intensively studied in other organs, its physiological role in periodontal tissues is unclear. In this study we found that Trpv1(-/-) mice developed severe bone loss in an experimental model of periodontitis. Chemical ablation of TRPV1-expressing sensory neurons recapitulated the phenotype of Trpv1(-/-) mice, suggesting a functional link between neuronal TRPV1 signaling and periodontal bone loss. TRPV1 activation in gingival nerves induced production of the neuropeptide, calcitonin gene-related peptide (CGRP), and CGRP treatment inhibited osteoclastogenesis in vitro. Oral administration of the TRPV1 agonist, capsaicin, suppressed ligature-induced bone loss in mice with fewer tartrate-resistant acid phosphatase (TRAP)-positive cells in alveolar bone. These results suggest that neuronal TRPV1 signaling in periodontal tissue is crucial for the regulation of osteoclastogenesis via the neuropeptide CGRP. PMID- 27388774 TI - Biofunctionalizing nanofibers with carbohydrate blood group antigens. AB - A rapid and simple method of biofunctionalising nylon, cellulose acetate, and polyvinyl butyral electrospun nanofibers with blood group glycans was achieved by preparing function-spacer-lipid constructs and simply contacting them to fibers with a piezo inkjet printer. A series of water dispersible amphipathic glycan spacer constructs were synthesized representing a range ABO and related blood group antigens. After immediate contact of the amphipathic glycan-spacer constructs with nanofiber surfaces they self-assembled and were detectable by enzyme immunoassays with high sensitivity and specificity. PMID- 27388775 TI - A Validation Study of Adiponectin rs266729 Gene Variant with Type 2 Diabetes, Obesity, and Metabolic Phenotypes in a Taiwanese Population. AB - Previous data suggesting that a single nucleotide polymorphism (SNP), rs266729, in the adiponectin C1Q and collagen domain containing (ADIPOQ) gene was associated with type 2 diabetes (T2D) have been inconsistent, especially in Asian populations. In this replication study, we aimed to reassess whether the ADIPOQ rs266729 SNP is associated with T2D, obesity, and T2D/obesity-related metabolic traits in a Taiwanese population. A total of 1047 Taiwanese subjects were analyzed. The ADIPOQ rs266729 SNP was genotyped by the Taqman assay. T2D/obesity related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase, and fasting glucose were measured. Our data revealed that the ADIPOQ rs266729 SNP exhibited no association with T2D among the subjects. In addition, no evidence for an association with obesity (BMI ?27 kg/m2) was found for the ADIPOQ rs266729 SNP. Moreover, the ADIPOQ rs266729 SNP did not show any association with T2D/obesity-related metabolic traits among the complete subjects. However, we found an effect modification of obesity on the association between the ADIPOQ rs266729 SNP and total cholesterol (P = 0.00068) only in obese participants after adjusting for age, gender, BMI, and T2D status. Our study indicates that the ADIPOQ rs266729 SNP may influence T2D/obesity-related metabolic traits such as total cholesterol in obese Taiwanese subjects (but not in non-obese subjects). PMID- 27388776 TI - Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy. AB - BACKGROUND & AIMS: Minimal hepatic encephalopathy is associated with poor prognosis and mortality in patients with cirrhosis. We aimed at investigating whether bacterial-DNA translocation affects hyperammonaemia and neurocognitive scores in patients with mHE according to the use of lactulose. METHODS: Observational study including 72 mHE cirrhotic patients, as defined by a psychometric hepatic encephalopathy score (PHES)<-4 and/or a critical flicker frequency (CFF)<39 Hz. Bacterial-DNA, serum ammonia, pro-inflammatory cytokines and nitric oxide levels were evaluated. A second cohort of 40 lactulose-untreated patients were evaluated before and 6-month after lactulose administration (30-60 mL/d). RESULTS: In the first cohort, bacterial-DNA rate was significantly higher in patients without lactulose (39% vs 23%, P=.03). Serum ammonia and inflammatory markers were significantly increased in patients with bacterial-DNA, regardless the use of lactulose, and correlated with the amount of amplified bacterial-DNA. Neurocognitive scores were significantly worse in bacterial-DNA positive vs negative patients (PHES -7.6+/-1.1 vs -5.5+/-1.0; CFF 32.5+/-2.6 vs 36.2+/-2.8, P=.01). Lactulose was associated with improved neurocognitive scores in patients without bacterial-DNA. Serum ammonia levels inversely correlated with neurocognitive scores in patients with bacterial-DNA (PHES r=-.84; CFF r=-.72, P=.001). In the second cohort, lactulose reduced bacterial-DNA translocation (36% 16%, P=.02). Neurocognitive scores were significantly improved in bacterial-DNA positive patients who cleared bacterial-DNA during the period on lactulose. Serum ammonia levels correlated with both neurocognitive scores in patients with bacterial-DNA, either before or after lactulose. CONCLUSION: Bacterial-DNA translocation worsens neurocognitive scores in mHE patients and it is reduced by lactulose, enhancing the relevance of controlling bacterial antigen translocation in these patients. PMID- 27388777 TI - Vitamin D insufficiency in a boy with obsessive-compulsive disorder. AB - Vitamin D deficiency not only causes low bone mass but also may lead to neuropsychiatric disorders. In the present case, vitamin D supplementation reduced obsessive-compulsive disorder (OCD) symptoms associated with streptococcal infection in a 7-year-old boy. Sudden onset of symptoms, including excessive hand washing and fear of touching anything, had occurred 1 month before presentation. Although there are few studies on a possible causal relationship between vitamin D and neuropsychiatric disorders, the present report; together with previous data, suggest an etiological role of vitamin D-related immune processes. PMID- 27388778 TI - Identification of major Toxoneuron nigriceps venom proteins using an integrated transcriptomic/proteomic approach. AB - Endoparasitoids in the order Hymenoptera are natural enemies of several herbivorous insect pest species. During oviposition they inject a mixture of factors, which include venom, into the host, ensuring the successful parasitism and the development of their progeny. Although these parasitoid factors are known to be responsible for host manipulation, such as immune system suppression, little is known about both identity and function of the majority of their venom components. To identify the major proteins of Toxoneuron nigriceps (Hymenoptera: Braconidae) venom, we used an integrated transcriptomic and proteomic approach. The tandem-mass spectrometric (LC-MS/MS) data combined with T. nigriceps venom gland transcriptome used as a reference database resulted in the identification of a total of thirty one different proteins. While some of the identified proteins have been described in venom from several parasitoids, others were identified for the first time. Among the identified proteins, hydrolases constituted the most abundant family followed by transferases, oxidoreductases, ligases, lyases and isomerases. The hydrolases identified in the T. nigriceps venom glands included proteases, peptidases and glycosidases, reported as common components of venom from several parasitoid species. Taken together, the identified proteins included factors that could potentially inhibit the host immune system, manipulate host physiological processes and host development, as well as provide nutrients to the parasitoid progeny, degrading host tissues by specific hydrolytic enzymes. The venom decoding provides us with information about the identity of candidate venom factors which could contribute to the success of parasitism, together with other maternal and embryonic factors. PMID- 27388779 TI - A Meta-Analytic Review of Social Identification and Health in Organizational Contexts. AB - We provide a meta-analytical review examining two decades of work on the relationship between individuals' social identifications and health in organizations (102 effect sizes, k = 58, N = 19,799). Results reveal a mean weighted positive association between organizational identification and health ( r = .21, T = .14). Analysis identified a positive relationship for both workgroup ( r = .21) and organizational identification ( r = .21), and in studies using longitudinal/experimental ( r = .13) and cross-sectional designs ( r = .22). The relationship is stronger (a) for indicators of the presence of well-being ( r = .27) than absence of stress ( r = .18), (b) for psychological ( r = .23) than physical health ( r = .16), (c) to the extent that identification is shared among group members, and (d) as the proportion of female participants in a sample decreases. Overall, results indicate that social identifications in organizations are positively associated with health but that there is also substantial variation in effect size strength. We discuss implications for theory and practice and outline a roadmap for future research. PMID- 27388780 TI - From underwear to non-equilibrium thermodynamics: physical chemistry informs the origin of life. PMID- 27388781 TI - Effect of a congested match schedule on immune-endocrine responses, technical performance and session-RPE in elite youth soccer players. AB - This study investigated the effects of a congested match schedule (7 matches played in 7 days) on steroid hormone concentrations, mucosal immunity, session rating of perceived exertion (S-RPE) and technical performance in 16 elite youth soccer players (14.8 +/- 0.4 years; 170.6 +/- 9.4 cm; 64.9 +/- 7 kg). No change was observed for salivary cortisol concentration across match time points (P = 0.33; effect size [ES] = 0.13-0.48). In contrast, there was a decrease in salivary testosterone and salivary IgA (SIgA) concentrations from the 1st compared with the last time point (P = 0.01 and 0.001, ES = 0.42 and 0.67, respectively). The SIgA concentration varied across time points (P < 0.001) with the highest value observed at the 3rd time point (rest day) (3rd vs all time point; ES = 0.47-0.73). No changes were observed for S-RPE across time points (P > 0.05). A higher number of tackles and interceptions were observed during the 4th match vs 1st and 7th matches (P < 0.001; ES = 2.25 and 1.90, respectively). The present data demonstrate that accumulated fatigue related to participation in a congested match schedule might induce a decrease in testosterone concentration in youth players and negatively affect their mucosal immunity and capacity to perform certain technical actions. PMID- 27388782 TI - Transaortic approach for transcatheter aortic valve replacement with other concomitant cardiac procedures in high-risk patients. AB - INTRODUCTION: The transaortic (TAo) approach has been proposed as an alternative to the transapical approach and can be used in concomitant procedures. We use the TAo transcatheter aortic valve replacement (TAVR) with other simultaneous cardiac procedures in high-risk patients who needed surgical management. MATERIALS AND METHODS: Between September 2013 and September 2015, nine consecutive high-risk patients with severe aortic valve stenosis (AR) and combined tricuspid valve disease or coronary artery disease were treated with TAo TAVR and simultaneous tricuspid valve repair or coronary artery bypass grafting. RESULTS: Mean postoperative pressure gradient at discharge was 13.4 +/- 3.2 mmHg and AR grade >2/4 was observed in one case (11.1%). New pacemaker implantation was required in one case (11.1%). Device success was achieved in 88.9% (n = 8), 30-day mortality was in 11.1% (n = 1), and intermediate mortality was in 33.3% (n = 3). CONCLUSION: TAo-TAVR approach offers definitive treatment to high-risk patients with coexisting complex cardiac lesions. Despite the relatively high 30-day and intermediate mortality, it is an option for selected high-risk patients. PMID- 27388783 TI - Rapid maxillary expansion in adults: Can multislice computed tomography help choose between orthopedic or surgical treatment? AB - INTRODUCTION: The aim of this study was to evaluate the accuracy of Multislice Computed Tomography (MSCT) in the detection resistance areas on the midpalatal suture (MPS) and thus to evaluate if MSCT could be a help in the kind of maxillary expansion to be used (pure orthodontic or surgically-aided) for the correction of transverse maxillary deficiencies in adults. METHODS: Ten MSCT were obtained from 10 MPS removed from fresh corpses (mean age: 79.4; extreme: 70-86). Three standardized radiological regions of interest (ROI) were identified on each MPS and were classified into "open" (group 1) or "closed" (group 2) by 3 independent radiologists. The 30 ROI were then histologically analyzed according to 3 criteria: mean suture width (MSW), obliteration index (OI) and interdigitation index (Ii). RESULTS: Nine ROI were classified in group 1 (closed) and 21 in group 2 (open). On the histological examination, the mean MSW was 396.9MUm in group 1 and 227.1MUm in group 2. OI was 3.098% and 9.309% and Ii was 1.25 and 1.34 respectively. Statistically significant difference between the 2 groups was only found for the MSW. We conclude that MSCT allows for the evaluation of the width of the MPS, but not for the evaluation of the other possible parameters of resistance we used. Therefore, it cannot predict precisely the amount of resistance in the MPS and is not suited for the choice between pure orthodontic or surgically-aided expansion. PMID- 27388784 TI - Lachrymal Gland Basal Cell Adenocarcinoma in a Ferret (Mustela putorius furo). AB - A 1 cm diameter mass was detected in the caudal superotemporal area of the left eye of a 6-year-old neutered male ferret (Mustela putorius furo). The mass and the left eye were removed surgically. Microscopical examination revealed a tumour of the adnexal gland of the eye that had invaded the surrounding ocular muscle. The tumour was composed of basal-type epithelial cells arranged in a solid, or occasionally tubular, pattern. Immunohistochemically, the tumour cells expressed cytokeratin and p63, but not smooth muscle actin. Based on these findings, the tumour was diagnosed as a basal cell adenocarcinoma of the lachrymal gland. In addition to the tumour, the retina of the left eye was detached and folded at the centre of the globe. This is the first report of a non-human case of basal cell adenocarcinoma of the lachrymal gland. PMID- 27388785 TI - Intrafamilial phenotypic variability of Specific Language Impairment. AB - We investigated language functions in 32 members of a four generation family with several members affected by Specific Language Impairment with an extensive language test battery in order to determine the prevalence, overlap, and homogeneity of linguistic deficits within one pedigree. In sum, one fourth of all family members tested fulfilled the criteria of Specific Language Impairment. Despite of some similarities in language abilities, different combinations of language deficits were observed, and individual language profiles varied substantially. Thus, though there is a high prevalence of language deficits in this family which raises the likelihood of a genetic origin of these deficits, and though all affected study participants displayed selective linguistic deficits with normal non-verbal functioning, language testing showed considerable variance in overlap and homogeneity of linguistic deficits. Thus, even in one genetic population, an underlying linguistic disorder manifests itself in different language abilities to a variant degree. PMID- 27388786 TI - Examining the contribution of motor movement and language dominance to increased left lateralization during sign generation in native signers. AB - The neural systems supporting speech and sign processing are very similar, although not identical. In a previous fTCD study of hearing native signers (Gutierrez-Sigut, Daws, et al., 2015) we found stronger left lateralization for sign than speech. Given that this increased lateralization could not be explained by hand movement alone, the contribution of motor movement versus 'linguistic' processes to the strength of hemispheric lateralization during sign production remains unclear. Here we directly contrast lateralization strength of covert versus overt signing during phonological and semantic fluency tasks. To address the possibility that hearing native signers' elevated lateralization indices (LIs) were due to performing a task in their less dominant language, here we test deaf native signers, whose dominant language is British Sign Language (BSL). Signers were more strongly left lateralized for overt than covert sign generation. However, the strength of lateralization was not correlated with the amount of time producing movements of the right hand. Comparisons with previous data from hearing native English speakers suggest stronger laterality indices for sign than speech in both covert and overt tasks. This increased left lateralization may be driven by specific properties of sign production such as the increased use of self-monitoring mechanisms or the nature of phonological encoding of signs. PMID- 27388787 TI - ABSTRACTS 2nd African College of Neuropsychopharmacology Congress 30 - 31 July 2016 Stellenbosch, Western Cape, South Africa. PMID- 27388788 TI - Depressive symptoms in older adults awaiting cataract surgery. AB - BACKGROUND: To assess the prevalence and predictors of depressive symptoms in a cohort of older adults awaiting cataract surgery and establish threshold vision at which depressive symptoms may emerge. DESIGN: Analysis of cross-sectional baseline data from a longitudinal cohort study of patients aged >=65 years on Australian public hospital cataract surgery waiting lists. PARTICIPANTS: We included 329 participants enrolled October 2013-August 2015. METHODS: Participants completed assessment of depressive symptoms, visual disability, quality of life, social participation and exercise frequency at least one month prior to cataract surgery. High and low contrast habitual vision was examined and systemic comorbidities noted. MAIN OUTCOME MEASURE: Depressive symptoms prior to first eye cataract surgery. RESULTS: The prevalence of depressive symptoms was 28.6% (94/329). Univariate analysis identified that participants with poorer high contrast vision, reduced quality of life, greater patient-reported visual disability, higher comorbidity score and who were taking more medications were more likely to exhibit signs of depression. Greater patient-reported visual disability (P = 0.02), reduced quality of life (P = 0.003) and a higher comorbidity score (P = 0.02) remained significantly associated with depressive symptoms in the multivariable model. Depressive symptoms emerged at a visual acuity of 6/12. CONCLUSIONS: These findings demonstrate a high prevalence of depressive symptoms in older persons with cataract, emerging at modest levels of vision loss. Efficient referral processes, timely surgical management, and improved screening and coordinated treatment of depressive symptoms during the surgical wait may minimize the negative psychological effects of cataract in this already vulnerable population. PMID- 27388789 TI - Is there any association of apolipoprotein E gene polymorphisms with metabolic syndrome in a young population of Croatian origin? AB - BACKGROUND: Apolipoprotein E has an important role in lipid metabolism and adipocyte activity and apo E gene (APOE) might serve as a potential determinant of metabolic syndrome (MetS). AIM: The aim of the presented study was to investigate the association between APOE polymorphism and MetS in young adult subjects of Croatian origin. METHODS: This study measured biochemical and anthropometric parameters of 149 young (aged 20-33) subjects. The APOE was genotyped by real-time PCR. RESULTS: No APOE genotype significantly increased the risk for development of MetS. Significant association was found between APOE polymorphism and elevated blood pressure (EBP) (p = .019). The carriers of the E4 allele had decreased risk for EBP (OR = 0.28, 95% CI) compared to E3 allele carriers (E3 allele vs others, chi2 = 7.08; p = .005). APOE alleles were significantly associated with the concentration of TC and LDL-C (chi2 = 12.11, p = .002 and chi2 = 15.76, p < .001, respectively). With diet as a modification covariate there was a significant correlation of APOE alleles with the concentrations of adiponectin and leptin (chi2 = 7.076; p = .029 and chi2 = 7.46; p = .024, respectively). CONCLUSION: Although APOE variants were not confirmed as the risk factor for development of MetS, the APOE alleles were associated with some of the metabolic parameters in young Croatian subjects. The relation of APOE alleles with a concentration of adiponectin and leptin depends on the diet intake. PMID- 27388790 TI - Synthesis and characterization of crosslinked polyisothiouronium methylstyrene nanoparticles of narrow size distribution for antibacterial and antibiofilm applications. AB - BACKGROUND: Isothiouronium salts are well known in their variety of antimicrobials activities. The use of polymeric biocides, polymers with antimicrobial activities, is expected to enhance the efficacy of some existing antimicrobial agents, thus minimizing the environmental problems accompanying conventional antimicrobials. METHODS: The current manuscript describes the synthesis and characterization of crosslinked polyisothiouronium methylstyrene (PITMS) nanoparticles (NPs) of narrow size distribution by dispersion co polymerization of the monomer isothiouronium methylstyrene with the crosslinking monomer ethylene glycol dimetacrylate. RESULTS AND DISCUSSION: The effect of total monomer, crosslinker and initiator concentrations on the size and size distribution of the formed NPs was also elucidated. The bactericidal activity of PITMS NPs of 67 +/- 8 nm diameter was illustrated for 4 bacterial pathogens: Listeria innocua, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. In order to demonstrate the potential of these PITMS NPs as inhibitor of biofilm formation, polyethylene terephthalate (PET) films were thin-coated with the PITMS NPs. The formed PET/PITMS films reduced the viability of the biofilm of Listeria by 2 orders of magnitude, making the coatings excellent candidates for further development of non-fouling surfaces. In addition, PITMS NP coatings were found to be non-toxic in HaCaT cells. CONCLUSIONS: The high antibacterial activity and effective inhibition of bacterial adsorption indicate the potential of these nanoparticles for development of new types of antibacterial and antibiofilm additives. PMID- 27388792 TI - The clinical potential of low-level C-peptide secretion. AB - INTRODUCTION: In all forms of diabetes, especially so in Type 1 diabetes (T1D), beta cell function is crucial for the course. The interest for residual beta cell function has been meagre, but increased in recent years with interventions to preserve function. Areas covered: Importance and clinical use of C-peptide in Type 1 diabetes. Data for this review were identified by searches of PubMed, and references from relevant articles using the search terms: "type 1 diabetes", "C peptide", "beta cell function", "HbA1c", quality of life", "complications". Abstracts and reports from meetings were not included. Expert commentary: C peptide may help to get a correct diagnosis, and it is of practical clinical value to know degree of residual insulin secretion to diminish the risk of severe hypoglycaemia and ketoacidosis. Evidence shows that even a quite reduced beta cell function may play an important role for quality of life, for metabolic balance/control, possibility to avoid complications and even for long-term survival. Furthermore, the evidence is increasing for C-peptide being a hormone per se. PMID- 27388791 TI - Fluorescence bimolecular complementation enables facile detection of ribosome assembly defects in Escherichia coli. AB - Assembly factors promote the otherwise non-spontaneous maturation of ribosome under physiological conditions inside the cell. Systematic identification and characterization of candidate assembly factors are fraught with bottlenecks due to lack of facile assay system to capture assembly defects. Here, we show that bimolecular fluorescence complementation (BiFC) allows detection of assembly defects that are induced by the loss of assembly factors. The fusion of N and C terminal fragments of Venus fluorescent protein to the ribosomal proteins uS13 and uL5, respectively, in Escherichia coli facilitated the incorporation of the tagged uS13 and uL5 onto the respective ribosomal subunits. When the ribosomal subunits associated to form the 70S particle, the complementary fragments of Venus were brought into proximity and rendered the Venus fluorescent. Assembly defects that inhibit the subunits association were provoked by either the loss of the known assembly factors such as RsgA and SrmB or the presence of small molecule inhibitors of ribosome maturation such as Lamotrigine and several ribosome-targeting antibiotics and these showed abrogation of the fluorescence complementation. This suggests that BiFC can be employed as a surrogate measure to detect ribosome assembly defects proficiently by circumventing the otherwise cumbersome procedures. BiFC thus offers a facile platform not only for systematic screening to validate potential assembly factors but also to discover novel small molecule inhibitors of ribosome assembly toward mapping the complex assembly landscape of ribosome. PMID- 27388793 TI - Adjunct analgesic drugs to local anaesthetics for neuroaxial blocks in children. AB - PURPOSE OF REVIEW: This article reviews various adjunct drugs used in the context of neuroaxial blocks in children and to provide a literature and evidence-based suggestion for the rational use of such adjuncts. RECENT FINDINGS: Contrary to plain local anaesthetics, preservative-free morphine and clonidine, ketamine in neonatal rodents has been found to enhance apoptosis in the spinal cord. Dexmedetomidine has been shown to be equally effective as clonidine as an adjunct to caudal blocks. Systemic dexamethasone is as effective as if it is co administered together with the local anaesthetic in the context of neural blockade. SUMMARY: Alpha-2 adrenoceptor agonists currently represent the most versatile and well-tolerated adjunct for neuroaxial blockade in children. Preservative-free morphine may be indicated in certain situations but the risk for respiratory depression and other disturbing side-effects must be taken into account. Preservative-free ketamine is an effective adjunct to caudal blockade in children but the use should be restricted to children older than 1 year of age. All other drugs must still be regarded as experimental and should not be used outside clinical trials. PMID- 27388794 TI - Ultrasound indications for chronic pain management: an update on the most recent evidence. AB - PURPOSE OF REVIEW: The ability of ultrasound to provide detailed anatomic visualization while avoiding radiation exposure continues to make it an appealing tool for many practitioners of chronic pain management. This review will present the most recent evidence regarding the use of ultrasound-guidance for the performance of interventional procedures in the treatment of chronic pain. RECENT FINDINGS: For a variety of different procedures, studies continue to compare ultrasound-guided techniques to commonly used fluoroscopic or landmark-based techniques. Small, randomized controlled trials are beginning to demonstrate that ultrasound-guided approaches to interventional pain procedures can be as well tolerated and effective as the traditionally used techniques, while providing some potential advantages in terms of decreased radiation exposure, avoidance of vascular structures, and in some cases, improved efficiency and decreased rates of adverse effects. SUMMARY: Despite continued interest in ultrasound-guided techniques for chronic pain management procedures, the evidence is still limited mainly to small, randomized trials and case series. For some procedures, such as stellate ganglion block and peripheral joint injections, recent evidence appears to be tilting in favor of ultrasound-guidance as the preferred technique, though fluoroscopy continues to be a much more reliable method for detection of intravascular uptake of injectate. PMID- 27388795 TI - Patient engagement impacts glycemic management with vildagliptin and vildagliptin/metformin (single pill) regimens in type 2 diabetes mellitus (the GLORIOUS study). AB - AIMS: To evaluate the real-world effectiveness of vildagliptin and vildagliptin/metformin, combined with patient engagement, on glycemic outcomes. Patient engagement included both clinicians' engaging patients through education and counseling; and patients' self-engagement through disease awareness, lifestyle changes, and medication adherence. METHODS: Prospective, observational, open-label, multi-center, pharmacoepidemiologic study of type 2 diabetes mellitus (T2DM) patients treated de novo with vildagliptin or vildagliptin/metformin. Data were collected at baseline (treatment initiation), 105+/-15d, and >=145d. RESULTS: The evaluable sample included 896 mainly male (58%), overweight (mean+/ SD BMI=30.3+/-5.4kg/m2), in later middle age (mean+/-SD age=64+/-11years) patients. Over the three visits, mean(+/-SD) HbA1c levels declined from 8.1%(+/ 1.0) to 7.3%(+/-1.0) to 7.2%(+/-0.9); HbA1c control rates rose from 7% to 36% to 43%. Mean+/-SD FPG levels decreased from 170(+/-49) to 141(+/-41) to 139(+/ 42)mg/dL; control rates increased from 12% to 39% to 43% (all p<0.0001). Weight decreased nominally by 2kg (p=0.0290) and BMI by 0.8kg/m2 (p<0.0001). Modeling showed patient engagement activities by clinicians and by patients to be major determinants of glycemic outcomes. No unknown safety signals were detected. CONCLUSIONS: Vildagliptin and vildagliptin/metformin are effective and safe oral agents in the management of T2DM, especially if part of a treatment program with active patient engagement by clinicians and empowered patients. PMID- 27388796 TI - Physicians frequently fail to de-intensify treatment in older patients with diabetes and very low haemoglobin A1c or blood pressure. PMID- 27388797 TI - Benefits of blood pressure lowering are seen across levels of baseline blood pressure, comorbidity and drug class. PMID- 27388798 TI - Risk of vascular events is lower than expected in patients with transient ischaemic attack or minor stroke treated promptly by stroke specialists. PMID- 27388799 TI - Fusion in degenerative spondylolisthesis becomes controversial...again. PMID- 27388800 TI - In H. pylori- infected patients second-line treatment with sequential levofloxacin therapy was more effective than levofloxacin triple therapy but was still suboptimal. PMID- 27388801 TI - Response to letter from Professor Tapio Vehmas. PMID- 27388802 TI - Study raises new doubts regarding the hypothesised health benefits of 'moderate' alcohol use. PMID- 27388803 TI - Schizotypy and auditory mismatch negativity in a non-clinical sample of young adults. AB - Schizophrenia may be conceptualised using a dimensional approach to examine trait like expression such as schizotypy within non-clinical populations to better understand pathophysiology. A candidate psychosis-risk marker, the auditory mismatch negativity (MMN) is thought to index the functionality of glutamatergic NMDA receptor mediated neurotransmission. Although the MMN is robustly reduced in patients with schizophrenia, the association between MMN and schizotypy in the general population is under-investigated. Thirty-five healthy participants completed the Schizotypal Personality Questionnaire (SPQ) and a multi-feature MMN paradigm (standards 82%, 50ms, 1000Hz, 80dB) with duration (100ms), frequency (1200Hz) and intensity (90dB) deviants (6% each). Spearman's correlations were used to explore the association between schizotypal personality traits and MMN amplitude. Few associations were identified between schizotypal traits and MMN. Higher Suspiciousness subscale scores tended to be correlated with larger frequency MMN amplitude. A median-split comparison of the sample on Suspiciousness scores showed larger MMN (irrespective of deviant condition) in the High compared to the Low Suspiciousness group. The trend-level association between MMN and Suspiciousness is in contrast to the robustly attenuated MMN amplitude observed in schizophrenia. Reductions in MMN may reflect a schizophrenia-disease state, whereas non-clinical schizotypy may not be subserved by similar neuropathology. PMID- 27388804 TI - Cumulative trauma, adversity and grief symptoms associated with fronto-temporal regions in life-course persistent delinquent boys. AB - Delinquent youth have substantial trauma exposure, with life-course persistent delinquents [LCPD] demonstrating notably elevated cross-diagnostic psychopathology and cognitive deficits. Because adolescents remain in the midst of brain and neurocognitive development, tailored interventions are key to improving functional outcomes. This structural magnetic resonance imaging study compared neuroanatomical profiles of 23 LCPD and 20 matched control adolescent boys. LCPD youth had smaller overall gray matter, and left hippocampal, volumes alongside less cortical surface area and folding within the left pars opercularis and supramarginal cortex. LCPD youth had more adversity-related exposures, and their higher Cumulative Trauma, Adversity and Grief [C-TAG] symptoms were associated with less surface area and folding in the pars opercularis and lingual gyrus. Neuroanatomical differences between LCPD and control youth overlap with data from both maltreatment and antisocial literatures. The affected left frontal regions also share connections to language- and executive-related functions, aligning well with LCPD youths' cognitive and behavioral difficulties. These data also dovetail with research suggesting the possibility of neurodevelopmental delays or disruptions related to cumulative adversity burden. Thus, concurrent treatment of LCPD youths' C-TAG symptoms and, cognitive deficits with overlapping neuroanatomical bases, may be most effective in improving outcomes and optimizing neurodevelopmental trajectories. PMID- 27388806 TI - Corrosion behaviours of the dental magnetic keeper complexes made by different alloys and methods. AB - The keeper and cast dowel-coping, as a primary component for a magnetic attachment, is easily subjected to corrosion in a wet environment, such as the oral cavity, which contains electrolyte-rich saliva, complex microflora and chewing behaviour and so on. The objective of this in vitro study was to examine the corrosion resistance of a dowel and coping-keeper complex fabricated by finish keeper and three alloys (cobalt-chromium, CoCr; silver-palladium-gold, PdAu; gold-platinum, AuPt) using a laser-welding process and a casting technique. The surface morphology characteristics and microstructures of the samples were examined by means of metallographic microscope and scanning electron microscope (SEM). Energy-dispersive spectroscopy (EDS) with SEM provided elements analysis information for the test samples after 10% oxalic acid solution etching test. Tafel polarization curve recordings demonstrated parameter values indicating corrosion of the samples when subjected to electrochemical testing. This study has suggested that massive oxides are attached to the surface of the CoCr-keeper complex but not to the AuPt-keeper complex. Only the keeper area of cast CoCr keeper complex displayed obvious intergranular corrosion and changes in the Fe and Co elements. Both cast and laser-welded AuPt-keeper complexes had the highest free corrosion potential, followed by the PdAu-keeper complex. We concluded that although the corrosion resistance of the CoCr-keeper complex was worst, the keeper surface passive film was actually preserved to its maximum extent. The laser-welded CoCr- and PdAu-keeper complexes possessed superior corrosion resistance as compared with their cast specimens, but no significant difference was found between the cast and laser-welded AuPt-keeper complexes. The Fe-poor and Cr-rich band, appearing on the edge of the keeper when casting, has been proven to be a corrosion-prone area. PMID- 27388807 TI - ColoNav: patient navigation for colorectal cancer screening in deprived areas - Study protocol. AB - BACKGROUND: The mass colorectal cancer screening program was implemented in 2008 in France, targeting 16 million French people aged between 50 and 74. The current adhesion is insufficient and the participation rate is even lower among the underserved population, increasing health inequalities within our health care system. Patient Navigation programs have proved their efficiency to promote the access to cancer screening and diagnosis. METHODS/DESIGN: The purpose of the study is to assess the implementation of a patient navigation intervention that has been described in another cultural environment and another health care system. The main objective of the program is to increase the colorectal cancer screening participation rate among the deprived population through the intervention of a navigator to promote the Fecal Occult Blood Test (FOBT) and complementary exams. We performed a multisite cluster randomized controlled trial, with three groups (one experimental group and two control groups) for 18 months. DISCUSSION: The study attempts to give a better understanding of the adhesion barriers to colorectal cancer screening among underserved populations. If this project is cost-effective, it could create a dynamic based on peer approaches that could be developed for other cancer screening programs and other chronic diseases. TRIAL REGISTRATION: NCT02369757. PMID- 27388805 TI - Impact of obesity on taste receptor expression in extra-oral tissues: emphasis on hypothalamus and brainstem. AB - Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the alpha-subunits of the associated signalling complex (alphaGustducin, Galpha14 and alphaTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and alpha-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Galpha14, alphaTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Galpha14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem. PMID- 27388808 TI - Establishment and characterization of buffalo fetal fibroblasts induced with human telomerase reverse transcriptase. AB - Fetal fibroblasts are often used as donor cells for SCNT, but their short lifespan greatly limits this application. To provide stable and long-lifespan cells, buffalo fetal fibroblasts (BFFs) transfected with human telomerase reverse transcriptase (hTERT). The hTERT-transfected BFFs (hTERT-BFFs) were evaluated by qRT-PCR, Western blot, karyotype analysis, telomerase activity assay, growth curve assay, flow cytometry, and soft agar assay. The development of SCNT embryos derived from hTERT-BFFs was also assessed in vitro. The morphology of hTERT-BFFs was similar to the nontransfected BFFs, and the karyotype of hTERT-BFFs was normal at passage 30. The hTERT-BFFs at passage 4 and 30 had higher telomerase activity and extended proliferative lifespan with an increase in cell population at S phase when compared with nontransfected BFFs at passage 5 and 30. The mRNA expression of p53 in hTERT-BFFs at passage 5 and 30 remained unchanged when compared with nontransfected BFFs at passage 5, whereas the mRNA expression of p53 in the nontransfected BFFs at passage 30 was increased. Soft agar assay showed that hTERT-BFFs at passage 30 were not a malignant phenotype. Significantly, more SCNT embryos derived from hTERT-BFFs at passage 5 and 30 developed to blastocysts in comparison with BFFs at passage 30. The Caudal type homeobox 2 and Connexin 43 genes were indicated to involve in the development of cloned embryos. These results indicate that transfection of BFFs with hTERT can extend their lifespan and retain their basic and key biological characteristics in the status of primary BFFs. PMID- 27388809 TI - Direct planting of ultrafine MoO2+delta nanoparticles in carbon nanofibers by electrospinning: self-supported mats as binder-free and long-life anodes for lithium-ion batteries. AB - Three-dimensional (3D) interconnected carbon nanofibrous mats containing well dispersed MoO2+delta nanocrystals are fabricated through a facile electrospinning route followed by thermal treatment in N2. The resulting nanostructured monolithic hybrid mat made of C/MoO2+delta nanofibers exhibits superior Li storage performances, when evaluated as a free-standing anode material. At a current density of 200 mA g(-1), a reversible capacity as high as 876.9 mA h g( 1) is achieved after 250 cycles. A capacity of 447.9 mA h g(-1) could still be maintained after 1000 cycles even at a high current density of 2000 mA g(-1), indicating high rate capability and cyclability. The attractive electrochemical performances of the as-obtained 3D C/MoO2+delta networks may benefit from the synergistic effects of the unique nanoarchitectures and the integrity of the electrodes. Monodispersed MoO2+delta nanocrystals encapsulated in carbon nanofibers not only provide interfacial storage but also improve the transport kinetics of electrons and lithium ions. PMID- 27388810 TI - Editorial Comment to Stratified analysis of 800 Asian patients after robot assisted radical prostatectomy with a median 64 months of follow up. PMID- 27388811 TI - Nanoformulations of a potent copper-based aquaporin inhibitor with cytotoxic effect against cancer cells. AB - AIM: Development of liposomal formulations of Cuphen, a potent copper-based aquaporin inhibitor with therapeutic potential against melanoma and colon cancer. MATERIALS & METHODS: Cuphen was incorporated into liposomes using the dehydration rehydration method. The ability of Cuphen to induce cancer cell death was evaluated by MTS and ViaCount assays. In vivo toxicity studies were performed in BALB/c mice. RESULTS: In vitro studies illustrated the antiproliferative effects of Cuphen in different cancer cell lines, in free form or after incorporation into liposomes. In vivo studies revealed no toxic effects after parenteral administration of Cuphen liposomes. CONCLUSIONS: Cuphen liposomes are highly attractive to be further tested in murine models due to the possibility of stabilizing and specifically deliver this metallodrug to tumor sites. PMID- 27388813 TI - Role of the 3-Vessel and Trachea View in Antenatal Detection of Tetralogy of Fallot. AB - Prenatal diagnosis of tetralogy of Fallot remains less frequent compared to other major congenital heart defects. In this study, we examined how often the 3-vessel and trachea view was abnormal in a large series of prenatally diagnosed cases of tetralogy of Fallot. In addition, we compared its sensitivity to that of the traditional outflow tract views for detection of tetralogy of Fallot. We found that both views were abnormal in all fetuses with tetralogy of Fallot, showing reversed aortic-to-pulmonary valve and aortic arch isthmus-to-ductus arteriosus ratios in the outflow tract and 3-vessel and trachea views, respectively. However, as a single measured marker, the enlarged aortic arch isthmus on the 3 vessel and trachea view appears to be the most sensitive for tetralogy of Fallot. PMID- 27388812 TI - Description and Comparison of the Sonographic Characteristics of Poorly Differentiated Thyroid Carcinoma and Anaplastic Thyroid Carcinoma. AB - OBJECTIVES: Although poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma account for a substantial portion of the morbidity and mortality associated with thyroid cancer, a chance of a cure exists with aggressive treatment, especially in patients with poorly differentiated thyroid carcinoma. The goal of this study was to evaluate the sonographic characteristics of poorly differentiated thyroid carcinoma and to compare the sonographic findings of poorly differentiated and anaplastic thyroid carcinomas. METHODS: The study included 29 patients with 30 poorly differentiated thyroid carcinomas and 26 patients with 26 anaplastic thyroid carcinomas. Two radiologists retrospectively reviewed sonographic findings. Clinical and sonographic findings were compared between poorly differentiated and anaplastic thyroid carcinomas by univariate and multivariate analyses. RESULTS: In the group of patients with poorly differentiated thyroid carcinoma, the mean age was 53.7 years (range, 14 73 years), and the mean tumor size was 3.6 cm (range, 0.6-10.0 cm). The common sonographic findings of poorly differentiated thyroid carcinoma were heterogeneous echogenicity (93.3%), solitary nodules (80.0%), a circumscribed margin (63.3%), an oval-to-round shape (63.3%), and hypoechogenicity (60.0%). A circumscribed margin (P = .003) and an oval-to-round shape (P = .015) were significantly more frequent in poorly differentiated thyroid carcinoma than in anaplastic thyroid carcinoma. In the multivariate analysis, only the circumscribed margin on sonography was an independent predicting factor for poorly differentiated thyroid carcinoma (odds ratio, 4.642). CONCLUSIONS: Both poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma commonly present as a relatively large malignant mass on sonography; however, poorly differentiated thyroid carcinoma showed a significantly higher incidence of a circumscribed margin and an oval-to-round shape than anaplastic thyroid carcinoma. Knowledge of sonographic characteristics will be useful for differentiation of poorly differentiated and anaplastic thyroid carcinomas. PMID- 27388814 TI - Comparing Quantitative Immunohistochemical Markers of Angiogenesis to Contrast Enhanced Subharmonic Imaging. AB - OBJECTIVES: Different methods for obtaining tumor neovascularity parameters based on immunohistochemical markers were compared to contrast-enhanced subharmonic imaging (SHI). METHODS: Eighty-five athymic nude female rats were implanted with 5 * 10(6) breast cancer cells (MDA-MB-231) in the mammary fat pad. The contrast agent Definity (Lantheus Medical Imaging, North Billerica, MA) was injected, and SHI was performed using a modified Sonix RP scanner (Analogic Ultrasound, Richmond, British Columbia, Canada) with a L9-4 linear array (transmitting/receiving frequencies, 8/4 MHz). Afterward, specimens were stained for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase 2 (COX-2). Tumor neovascularity was assessed in 4 different ways using a histomorphometry system (*100 magnification: (1) over the entire tumor; (2) in small sub-regions of interest (ROIs); (3) in the tumor periphery and centrally; and (4) in 3 regions of maximum marker expression (so-called hot spots). Results from specimens and from SHI were compared by linear regression. RESULTS: Fifty-four rats (64%) showed tumor growth, and 38 were successfully imaged. Subharmonic imaging depicted the tortuous morphologic characteristics of tumor neovessels and delineated small areas of necrosis. The immunohistochemical markers did not correlate with SHI measures over the entire tumor area or over small sub-ROIs (P > .18). However, when the specimens were subdivided into central and peripheral regions, COX-2 and VEGF correlated with SHI in the periphery (r = -0.42; P = .005; and r = -0.32; P = .049, respectively). CONCLUSIONS: When comparing quantitative contrast measures of tumor neovascularity to immunohistochemical markers of angiogenesis in xenograft models, ROIs corresponding to the biologically active region should be used to account for tumor heterogeneity. PMID- 27388815 TI - Ultrasound Versus Computed Tomographic Guidance for Percutaneous Biopsy of Chest Lesions. AB - OBJECTIVES: To compare ultrasound (US) versus computed tomography (CT) for primary guidance during needle biopsy of chest lesions. METHODS: Institutional Review Board approval was obtained for this Health Insurance Portability and Accountability Act-compliant retrospective study, and the need for informed consent was waived. All US- and CT-guided chest biopsy procedures performed between January 1, 2012, and October 15, 2014, at our institution were reviewed, and all procedures targeting peripheral intrathoracic and chest wall lesions were included. Axillary lesions, lung lesions without peripheral pleural contact, and mediastinal lesions without a transcutaneous US window were excluded. Radiologic, pathologic, and clinical records were reviewed. RESULTS: Fifty-five procedures with primary US guidance (23 lung, 6 pleural, 2 mediastinal, and 24 chest wall) and 130 CT procedures (88 lung, 10 pleural, 7 mediastinal, and 25 chest wall) were performed. Diagnostic samples were obtained in 98% (54 of 55) of US procedures and 87% (113 of 130) of CT procedures (P = .02). Pneumothorax requiring treatment occurred in 2% (1 of 55) of US procedures and 5% (7 of 130) of CT procedures (P = .25). Computed tomographic localization was used in 29% (16 of 55) of US procedures. Nevertheless, the average patient radiation dose was significantly less in US procedures (182 mGy-cm) versus CT procedures (718 mGy cm; P< .01). The average procedure time was 40 minutes for US and 38 minutes for CT (P = .39). The average lesion size was 4.5 cm for US and 4.9 cm for CT (P = .14). CONCLUSIONS: During biopsy of peripheral intrathoracic lesions and chest wall lesions, primary US guidance resulted in a higher likelihood of a diagnostic sample and a decreased patient radiation dose compared with CT guidance. PMID- 27388816 TI - Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion. AB - Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED. PMID- 27388817 TI - Potential impact of clinical use of noninvasive FFRCT on radiation dose exposure and downstream clinical event rate. AB - OBJECTIVE: This study aims to determine the potential impact of introducing noninvasive fractional flow reserve based on coronary computed tomography angiography (CTA) into clinical practice, with respect to radiation dose exposure and downstream event rate. METHODS: We modeled a population of 1000 stable, symptomatic patients with suspected coronary artery disease, using the disease prevalence from the CONFIRM registry to estimate the pretest likelihood. Four potential clinical pathways were modeled based on the first noninvasive diagnostic test performed: (1) dobutamine echo; (2) single-photon emission computerized tomography (SPECT); (3) coronary CTA; and (4) CTA+FFRCT and leading to possible invasive coronary angiography. The posttest likelihood of testing positive/negative by each test was based on the presenting disease burden and diagnostic accuracy of each test. RESULTS: The dobutamine echo pathway resulted in the lowest radiation dose of 5.4 mSv, with 4.0 mSv from angiography and 1.4 mSv from percutaneous coronary intervention (PCI). The highest dose was with SPECT, with 26.5 mSv. The coronary computed tomography angiography (cCTA) pathway demonstrated a dose of 14.2 mSv, 3.7 mSv from cCTA, 7.7 mSv from angiography, and 2.8 mSv from PCI. The CTA+FFRCT pathway exhibited a radiation dose of 9.7 mSv, 3.7 mSv for cCTA, 4.2 mSv for angiography, and 1.8 mSv for PCI. Radiation dose exposure for CTA+FFRCT was lower than for SPECT (P<.001). The CTA+FFRCT pathway resulted in the lowest projected death/myocardial infarction rate at 1 year (2.44%) while the dobutamine stress pathway had the highest 1-year event rate (2.84%). CONCLUSION: Our analysis suggests that integrating FFRCT into the CTA clinical pathway may result in reduced cumulative radiation exposure, while promoting favorable clinical outcomes. PMID- 27388818 TI - Effect of essential oils on meat and fat qualities of crossbred young bulls finished in feedlots. AB - Twenty-seven animals (1/2 Angus - 1/2 Nellore) were fed for four months with one of the following diets: without addition of essential oils (E0.0), with 3.5 (E3.5) or 7 (E7.0) g/animal/day of an essential oil blend (oregano, garlic, lemon, rosemary, thyme, eucalyptus and sweet orange). Chemical composition, fatty acid profile and meat color were evaluated in Longissimus muscle. In addition, the effects of aging (one, seven and 14days) on the meat water holding capacity, texture and lipid oxidation were evaluated. Essential oils had no effect on chemical and fatty acid composition, meat color, water holding capacity or texture, but an inclusion of 3.5g/day decreased lipid oxidation. The addition of 7.0g/animal/day had a pro-oxidant effect on meat during aging and resulted in higher values for lipid oxidation at 14days of aging. Aging significantly affected thawing losses and texture. A dose of 3.5g/animal/day could be recommended in feedlot animals, but greater doses could have a pro-oxidant effect. PMID- 27388819 TI - Effects of adding red wine on the physicochemical properties and sensory characteristics of uncured frankfurter-type sausage. AB - The aim of this work was to evaluate the quality and sensory characteristics of RTE frankfurter-type sausage cured with celery juice powder and including red wine. Four frankfurter treatments including a conventionally cured treatment without red wine (control) and three treatments cured with pre-converted vegetable juice powder and 0%, 5% or 10% (v/w) red wine were prepared. Results showed that adding 5% red wine increased the a*-value, and the textural resilience, cohesiveness and springiness of the frankfurters, as well as decreased lipid/protein oxidation of the final products. Added wine also introduced new volatiles (alcohol and ester compounds) to the frankfurters. The principal component (PC) analysis showed that the pre-converted vegetable juice powder achieved the same effects as the conventional curing agents for typical frankfurter properties. However, the addition of excess amounts of red wine (10%) to the meat batter decreased the pH of meat batter and accelerated lipid oxidation. PMID- 27388820 TI - Dedicated Bifurcation Stent for the Treatment of Bifurcation Lesions Involving Large Side Branches: Outcomes From the Tryton Confirmatory Study. AB - OBJECTIVES: The aim of this study was to prospectively study and confirm the safety and efficacy of the Tryton Side Branch Stent in the treatment of coronary artery bifurcations involving large side branches (SBs). BACKGROUND: The TRYTON Pivotal randomized controlled trial (RCT) was designed to compare the Tryton stent with standard provisional SB stenting in large vessels. The trial inadvertently enrolled patients with too small SBs (<2.25 mm). The overall trial did not meet its primary endpoint, because of an increased rate of periprocedural myocardial infarction in the Tryton stent arm. A post hoc analysis restricted to the intended population showed that the trial would have met its endpoint if only patients with SBs >=2.25 mm in diameter (by core laboratory quantitative coronary angiography) had been enrolled. METHODS: The Tryton Confirmatory Study was a prospective, single-arm extension of the TRYTON Pivotal RCT that enrolled an additional 133 patients treated with the Tryton Side Branch Stent. It was designed to confirm the results of the post hoc analysis and emphasized the inclusion of appropriately sized SBs. The primary endpoint was noninferiority with regard to periprocedural myocardial infarction (creatine kinase myocardial band 3 times the upper limit of normal) compared with a performance goal based on the TRYTON Pivotal RCT. RESULTS: Among the 133 enrolled patients, 132 (99.2%) had SBs >=2.25 mm. Baseline clinical and angiographic parameters were similar in this study and the RCT. Periprocedural myocardial infarction occurred in 10.5% of patients, which was numerically lower than the provisional group in the TRYTON Pivotal RCT (11.9%). The 95% confidence bounds did not extend beyond the pre defined performance goal of 17.9%, meeting the noninferiority primary endpoint. CONCLUSIONS: The Tryton Confirmatory Study, in conjunction with the post hoc analysis of the intended population in the TRYTON Pivotal RCT, supports the safety and efficacy of the Tryton Side Branch Stent for treatment of bifurcation lesions involving large SBs. PMID- 27388821 TI - Challenging the "Provisional" Technique for Coronary Bifurcation Lesions. PMID- 27388822 TI - Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry. AB - OBJECTIVES: The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI). BACKGROUND: The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized. METHODS: A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression. RESULTS: Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding. CONCLUSIONS: Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy. PMID- 27388823 TI - Bleeding Versus Clotting? Both Are Equally Bad After Percutaneous Coronary Intervention. PMID- 27388825 TI - Where Are the Boundaries for Transcatheter Valve Therapy? PMID- 27388824 TI - Transcatheter Mitral Valve Replacement in Native Mitral Valve Disease With Severe Mitral Annular Calcification: Results From the First Multicenter Global Registry. AB - OBJECTIVES: This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry. BACKGROUND: The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population. METHODS: We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR. RESULTS: From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 +/- 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 +/- 9.5%. The mean mitral gradient was 11.45 +/- 4.4 mm Hg and the mean mitral area was 1.18 +/- 0.5 cm(2). SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 +/- 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25). CONCLUSIONS: TMVR with balloon expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options. PMID- 27388827 TI - Lessons From Drive-By Left Atrial Appendage Occlusion. PMID- 27388826 TI - Predictors of Early (1-Week) Outcomes Following Left Atrial Appendage Closure With Amplatzer Devices. AB - OBJECTIVES: The aim of this study was to assess predictors of adverse 1-week outcomes and determine the effect of left atrial appendage (LAA) morphology following LAA closure (LAAC) with Amplatzer devices. BACKGROUND: Percutaneous LAAC is a valuable treatment option for stroke prevention in patients with atrial fibrillation. Determinants of procedural safety events with Amplatzer occluders are not well established, and the possibly interrelating effect of LAA anatomy is unknown. METHODS: Between 2009 and 2014, 500 consecutive patients with atrial fibrillation ineligible or at high risk for oral anticoagulation underwent LAAC using Amplatzer devices. Procedure- and device-related major adverse events (MAEs) were defined as the composite of death, stroke, major or life-threatening bleeding, serious pericardial effusion, device embolization, major access-site vascular complication, or need for cardiovascular surgery within 7 days following the intervention. RESULTS: Patients (mean age 73.9 +/- 10.1 years) were treated with Amplatzer Cardiac Plug (n = 408 [82%]) or Amulet (n = 92 [18%]) devices. Early procedural success was 97.8%, and MAEs occurred in 29 patients (5.8%). Independent predictors of MAEs included device repositioning (odds ratio: 9.13; 95% confidence interval: 2.85 to 33.54; p < 0.001) and left ventricular ejection fraction <30% (odds ratio: 4.08; 95% confidence interval: 1.49 to 11.20; p = 0.006), with no effect of device type or size. Angiographic LAA morphology, characterized as cauliflower (33%), cactus (32%), windsock (20%), or chicken wing (15%), was not associated with procedural success (p = 0.51) or the occurrence of MAEs (p = 0.78). CONCLUSIONS: In this nonrandomized study, procedural success of LAAC using Amplatzer devices was high. MAEs within 7 days were predicted by patient- and procedure-related factors. Although LAA morphology displayed substantial heterogeneity, outcomes were comparable across the spectrum of LAA anatomies. PMID- 27388829 TI - The Treatment of Superficial Femoral Artery In-Stent Restenosis: The Jury Is Still Out. PMID- 27388828 TI - Paclitaxel-Eluting Balloon Versus Standard Balloon Angioplasty in In-Stent Restenosis of the Superficial Femoral and Proximal Popliteal Artery: 1-Year Results of the PACUBA Trial. AB - OBJECTIVES: The hypothesis that paclitaxel-eluting balloon angioplasty provides higher 1-year patency rates in femoropopliteal artery in-stent restenosis compared with standard percutaneous transluminal angioplasty (PTA) was tested. BACKGROUND: Several trials have demonstrated that paclitaxel-eluting balloon angioplasty reduces late luminal loss in comparison with PTA. METHOD: In a prospective, randomized, single-blind, dual-center study, 74 patients with symptomatic peripheral artery disease due to in-stent restenosis were treated with either paclitaxel-based drug-eluting balloon (DEB) angioplasty (n = 35) or standard PTA (n = 39). Clinical outcomes and patency rates were assessed at 1, 6, and 12 months. RESULTS: The mean lesion length was 17.3 +/- 11.3 cm in the DEB group and 18.4 +/- 8.8 cm in the PTA group. A single major complication (bleeding) was observed once (1.4%). The mean ankle-brachial index before endovascular treatment was 0.65 +/- 0.16 in both groups and 0.79 +/- 0.2 versus 0.84 +/- 0.3 (p = 0.70, Student t test) in the DEB versus PTA group at 12 months. The 12-month primary patency rates were 40.7% (95% confidence interval [CI]: 0.26 to 0.64) versus 13.4% (95% CI: 0.05 to 0.36) (log-rank p = 0.02) in the DEB versus PTA group. The odds ratio for PTA over DEB angioplasty for experiencing an event was estimated at 2.8 (95% CI: 1.2 to 6.6). Freedom from clinically driven target lesion revascularization was 49.0% (95% CI: 0.32 to 0.75) versus 22.1% (95% CI: 0.10 to 0.48) (log-rank p = 0.11) in the DEB versus PTA group. Clinical improvement by >=1 Rutherford-Becker category was 68.8% versus 54.5% (p = 0.87) in the DEB versus PTA group at 12 months. CONCLUSIONS: When treating peripheral artery disease in patients with in-stent restenosis in the femoropopliteal artery, paclitaxel-eluting balloon angioplasty provides significantly higher patency rates than standard PTA. (Paclitaxel Balloon Versus Standard Balloon in In-Stent Restenoses of the Superficial Femoral Artery [PACUBA I Trial] [PACUBA 1]; NCT01247402). PMID- 27388830 TI - Sequential Proximal Optimizing Technique in Provisional Bifurcation Stenting With Everolimus-Eluting Bioresorbable Vascular Scaffold: Fractal Coronary Bifurcation Bench for Comparative Test Between Absorb and XIENCE Xpedition. AB - OBJECTIVES: The aim of this fractal bifurcation bench study was to compare provisional bifurcation stenting with a "re-POT" sequence, comprising a proximal optimizing technique (POT), side branch inflation, and final POT, between a bioresorbable vascular scaffold (BVS) and a metallic stent. BACKGROUND: Re-POT proved significantly better than kissing balloon inflation in maintaining circular geometry without overstretch in metal stents, while significantly reducing side branch ostium strut obstruction and global strut malapposition. This should be useful for BVSs, which are more easily breakable. METHODS: Twenty left main-like and 20 left anterior descending-like fractal coronary bifurcation bench models used 10 each 2.5 * 24 mm and 3.5 * 24 mm Absorb (Ab) BVSs and 10 each 2.5 * 24 mm and 3.5 * 24 mm XIENCE Xpedition (XX) metal stents, implanted by re-POT, with optical coherence tomographic analysis at each step and micro computed tomographic analysis of Ab devices to detect strut fracture. RESULTS: With Ab devices, re-POT reduced percentage strut malapposition close to XX rates (0.8 +/- 0.7% vs. 0.0 +/- 0.0%, p < 0.05; 3.5 +/- 1.7% vs. 0.3 +/- 0.6%, p < 0.05), conserving proximal circularity (elliptical ratio, 1.04 vs. 1.03 and 1.04 vs. 1.04; p = NS). Mean post-re-POT proximal expansion was 0.6 +/- 0.1 mm (+21.6 +/- 2.1%) for 2.5-mm and 1.0 +/- 0.1 mm (+23.6 +/- 2.2%) for 3.5-mm Ab devices, with only 1 strut fracture (left anterior descending-like bench). Side branch ostium strut obstruction was greater with Ab scaffolds than XX stents: 41.1 +/- 9.4% versus 16.4 +/- 8.1% (p < 0.05) and 31.8 +/- 3.2% versus 10.0 +/- 5.3% (p < 0.05), respectively, for 2.5- and 3.5-mm scaffolds and stents. Ab scaffolds showed 2 +/- 1% moderate but significant late recoil as of 1 h, reaching 4 +/- 2% by 24 h (p < 0.05). CONCLUSIONS: Re-POT optimized most Ab provisional bifurcation treatments, without fracture, respecting fractal geometry, and without exceeding 1.0-mm proximal differential diameter. PMID- 27388831 TI - Kissing, Snugging, or "Potting"?: The Evolution of Stenting Techniques in Bifurcations. PMID- 27388832 TI - STEMI After TAVR: Procedural Challenge and Catastrophic Outcome. PMID- 27388833 TI - Pre-Hospital Ticagrelor in ST-Segment Elevation Myocardial Infarction: Should the Hypothesis Be Re-Evaluated? PMID- 27388834 TI - Immediate Versus Delayed Invasive Intervention for Non-ST-Segment Elevation Myocardial Infarction Patients (RIDDLE-NSTEMI Study): A Game Changer for Interventional Cardiologists? PMID- 27388835 TI - Reply: Immediate Versus Delayed Invasive Intervention for Non-ST-Segment Elevation Myocardial Infarction Patients (RIDDLE-NSTEMI Study): A Game Changer for Interventional Cardiologists? PMID- 27388836 TI - Old Dogs/New Tricks. PMID- 27388837 TI - Use of Atmospheric Budget to Reduce Uncertainty in Estimated Water Availability over South Asia from Different Reanalyses. AB - Disagreements across different reanalyses over South Asia result into uncertainty in assessment of water availability, which is computed as the difference between Precipitation and Evapotranspiration (P-E). Here, we compute P-E directly from atmospheric budget with divergence of moisture flux for different reanalyses and find improved correlation with observed values of P-E, acquired from station and satellite data. We also find reduced closure terms for water cycle computed with atmospheric budget, analysed over South Asian landmass, when compared to that obtained with individual values of P and E. The P-E value derived with atmospheric budget is more consistent with energy budget, when we use top-of atmosphere radiation for the same. For analysing water cycle, we use runoff from Global Land Data Assimilation System, and water storage from Gravity Recovery and Climate Experiment. We find improvements in agreements across different reanalyses, in terms of inter-annual cross correlation when atmospheric budget is used to estimate P-E and hence, emphasize to use the same for estimations of water availability in South Asia to reduce uncertainty. Our results on water availability with reduced uncertainty over highly populated monsoon driven South Asia will be useful for water management and agricultural decision making. PMID- 27388838 TI - Effects of hydroxylysine on the growth and morphology of Rhizobium leguminosarum bv. phaseoli. AB - It was found that both bacteroids and free-living cells of Rhizobium leguminosarum bv. phaseoli were highly susceptible to hydroxylysine (Hyl) and the inhibition of RNA and/or protein synthesis caused by the hydroxyl residue of Hyl appeared to be responsible for the growth inhibition. The size of free-living cells was enlarged by the addition of Hyl and some cells reached around 5 MUm, which were close to the length of bacteroids. Under the same condition, the polyhydroxybutyrate (PHB) content in the cells was conspicuously increased. These results suggest that Hyl is not only a notable growth inhibitor of Rhizobium bacteria but also plays a role in a differentiation to bacteroids. PMID- 27388839 TI - Insecticidal Component in Thunberg Spiraea, Spiraea thunbergii, against Thrips palmi. AB - alpha-Methylene-gamma-butyrolactone (tulipalin A) was isolated and identified as an insecticidal component from thunberg spiraea, Spiraea thunbergii. This compound showed high insecticidal activity against Thrips palmi. PMID- 27388840 TI - Enantioselective Synthesis of a (+)-(2R, 3R)-1,4-Benzodioxane-7-carbaldehyde Derivative, a Key Intermediate in the Total Synthesis of Haedoxan Analogs. AB - (+)-(2R,3R)-7-Formyl-6-methoxy-2-methoxymethyl-3- (3,4-methylenedioxyphenyl)-2,3 dihydro-1,4-benzodioxin (2), a key building block for the total synthesis of haedoxan A, was synthesized from (4R)-4-(phenylmethyl)-2-oxazolidinone (3) in ten steps with a 12% overall yield. PMID- 27388841 TI - Xylanase Induction by L-Sorbose in a Fungus, Trichoderma reesei PC-3-7. AB - Xylanase induction by L-sorbose was studied in a resting cell system of a filamentous fungus, Trichoderma reesei PC-3-7, a hypercellulolytic mutant, and compared with that by other inducers. L-Sorbose induced xylanase activity as well as cellulase. It induced a higher level of xylanase activity than sophorose and xylose did. Three main xylanases, xylanase I (Xyn I), xylanase II (Xyn II), and a non-specific endoglucanase I (EG I), were separated using cation-exchange chromatography, and their activity were measured. Xyn II was induced in about the same proportion (60-80% of the total xylanase activity) by all inducers used. On the other hand, Xyn I was apparently induced by L-sorbose, xylose, and xylooligosaccharides, but only a little by sophorose. Northern blot analysis showed that L-sorbose induced Xyn I and Xyn II at the transcriptional level, and more xyn1 mRNA was transcribed after L-sorbose addition than after sophorose. These results suggested that the expressions of both Xyn I and Xyn II are regulated, at least in part, in a different manner. Furthermore, the Xyn I induction by L-sorbose indicated that an unknown common regulatory mechanism may exist between Xyn I and cellulase inductions. PMID- 27388842 TI - Degradation of Derivatives of N-Acetyl-D-glucosamine by Rhodococcus rhodochrous IFO 15564: Substrate Specificity and Its Application to the Synthesis of Allyl alpha-N-Acetyl-D-glucosaminide. AB - The substrate specificity was studied for the metabolic degradation of N-acetyl-D glucosamine (GlcNAc) derivatives by Rhodococcus rhodochrous IFO 15564 which possesses N-acetyl-D-glucosamine deacetylase as a key-step enzyme. This microorganism degraded a wide range of substrates with modified N-acyl groups. The metabolizing activity of this strain became low to the substrates substituted at 1,3,4,6-positions of GlcNAc, and GlcNAc itself was suggested to be metabolized via an open-chain aldehyde form. Based on these results, a simplified procedure for the isolation of allyl alpha-N-acetyl-D-glucosaminide from an alpha, beta anomeric mixture was developed by selectively hydrolyzing the beta-anomer with Jackbean beta-N-acetyl-D-glucosaminidase and subsequently degrading the resulting N-acetyl-D-glucosamine in the reaction mixture with this microorganism. PMID- 27388843 TI - Distribution of Threonine Aldolase Activity with Different Stereospecificities in Aerobic Bacteria. AB - Threonine aldolase activities (threonine acetaldehyde-lyase activity) with different stereospecificities toward 4 isomers of threonine were found in a variety of aerobic bacteria. The strains could be divided into three groups on the basis of the substrate specificity of a cell-free extract. The enzyme activities toward D-allo- and D-threonine were inhibited by EDTA, which suggested that a metal ion participates in the D-specific aldolase reaction. PMID- 27388844 TI - Glycolaldehyde Production from Ethylene Glycol with Immobilized Alcohol Oxidase and Catalase. AB - An enzymatic method for glycolaldehyde production from ethylene glycol was investigated using immobilized alcohol oxidase and catalase. Those enzymes were immobilized onto Chitopearl BCW 3501. When only alcohol oxidase was immobilized onto it, the apparent activity was 190 units/g in wet gel using methanol as the substrate. Tris-HCl buffer (1.5 M; pH 9.0) was selected based on a high stability of glycolaldehyde and a low production of glyoxal as a by-product. Under the optimum conditions, 0.97 M glycolaldehyde was formed from 1.0 M ethylene glycol and the ratio of glyoxal to glycolaldehyde was less than 1%. PMID- 27388845 TI - Aspartate Decarboxylation Encoded on the Plasmid in the Soy Sauce Lactic Acid Bacterium, Tetragenococcus halophila D10. AB - Tetragenococcus halophila D10 decarboxylates aspartate to alanine, but T. halophila D10 derivatives generated by a curing treatment could not (Asd(-) derivatives). We observed by electrophoresis three plasmid bands in T. halophila D10; all Asd(-) derivatives lost the largest of these bands. This plasmid, pD1, has two SalI sites. We cloned and sequenced the 10 kb SalI fragment. The DNA sequence suggests that this fragment contains the aspartate decarboxylating trait. PMID- 27388846 TI - Cationic Peroxidases Secreted from Cultured Cells May Localize to Apoplasts in Tobacco Plant Roots. AB - The transcripts for 38-kDa and 40-kDa cationic peroxidases of tobacco plants are accumulated in cultured cells, cultured roots, and roots of intact plants. In roots, 38-kDa and 40-kDa peroxidases appear to be localized to apoplasts, where peroxidase proteins may possibly be bound to the cell wall. PMID- 27388847 TI - Effects of Batatasin III and Its Analogs on Gibberellic Acid-Dependent alpha Amylase Induction in Embryoless Barley Seeds and on Cress Growth. AB - The effects of batatasin III and its analogs on gibberellic acid (GA3)-dependent alpha-amylase induction in embryoless barley seeds and on cress root-growth were examined. Batatasin III was most effective and caused 68% inhibition of alpha amylase induction at 4*10(-4) M, but its potency was low compared with that of abscisic acid. In the cress test, p-hydroxybibenzyl had high activity. PMID- 27388848 TI - Pesthetoxin, a New Phytotoxin Produced by the Gray Blight Fungus, Pestalotiopsis theae. AB - Pestalotiopsis theae is known to be a causal fungus for tea gray blight disease. Pesthetoxin was isolated from P. theae as a potent leaf-necrosis substance against tea. The structure of pesthetoxin was established principally by NMR studies to be of four different enolic forms, viz the pairs of internal tautomers (1a)/(1b) and (1c)/(1d) with external tautomerism between them. PMID- 27388849 TI - Practical Preparation of K-252a from a Fermentation Solution. AB - We developed a practical preparation procedure for K-252a by methylating K-252b on an industrial scale. The water-insoluble K-252a, which was present in the cell mass, was converted to the water-soluble K-252b Na salt in an alkaline solution. The obtained K-252b was methylated with dimethylsulfate in the presence of potassium carbonate in dimethylacetamide. We have already used this method to manufacture 90 kg of K-252b from the fermentation broth, and regenerated 65 kg of K-252a from K-252b. PMID- 27388850 TI - Formation of N-(1-Oxo-2,4,5,6-hydroxyhexyl)-2'-deoxyguanosine by the Reaction of 2'-Deoxyguanosine with 3-Deoxyglucosone. AB - 3-Deoxyglucosone (3DG) has weaker mutagenicity than methylglyoxal by the Ames test. 3DG reacted readily with 2'-deoxyguanosine (dG) in nucleosides. Two major products (G-A and G-B) were isolated and purified from the reaction mixture of 50 mM 3DG and 50 mM dG at 50 degrees C and pH 7.4 for 6d. G-A was identified as N-(1 oxo-2,4,5,6-hydroxyhexyl)-2'-deoxyguanosine. G-B was identified as a diastereomer of G-A. PMID- 27388851 TI - HPLC Analysis of Anomeric Formation and Cleavage Pattern by Chitinolytic Enzyme. AB - The reactions of N-acetylchitooligosaccharides with chitinolytic enzyme were analyzed by HPLC using a Tosoh TSK-Gel amide-80 column with 70% acetonitrile as an eluent. We separated alpha and beta anomeric forms of N acetylchitooligosaccharides, and obtain the following advantages of this HPLC method. 1. We can easily identify the reaction mechanism of chitinolytic enzymes by this method, distinguishing the inverting mechanism showing alpha anomer formation from the retaining mechanism showing beta anomer formation. 2. We can also estimate the cleavage patterns of N-acetylchitooligosaccharides by chitinolytic enzymes by using natural substrates. PMID- 27388852 TI - Imatinib ameliorates bronchiolitis obliterans via inhibition of fibrocyte migration and differentiation. AB - BACKGROUND: Imatinib, a tyrosine kinase inhibitor, has been proposed as a potential anti-fibrotic agent for fibroproliferative diseases, including bronchiolitis obliterans (BO). However, the underlying anti-fibrotic mechanisms of the agent remain unclear. We evaluated whether bone (BM)-derived progenitor cells, fibrocytes, might be a target of imatinib in the attenuation of BO. METHODS: We used a murine BO model induced by heterotopic tracheal transplantation and assessed the origin of fibroblasts by using green fluorescent protein-BM chimeric mice. We also evaluated the effects of imatinib on luminal obstruction and fibrocyte accumulation. The effects of imatinib on fibrocyte migration and differentiation were assessed by culturing fibrocytes in vitro. RESULTS: In the murine BO model, tracheal allografts showed epithelial injury and developed complete luminal occlusion 28 days after transplantation. Most of the mesenchymal cells that had accumulated in the tracheal allograft were derived from BM cells. Imatinib treatment ameliorated the airway luminal occlusion and significantly reduced the number of fibrocytes in the allografts. In vitro studies showed that imatinib inhibited migration of cultured blood fibrocytes via the platelet-derived growth factor/platelet-derived growth factor receptor axis. Imatinib also inhibited differentiation of fibrocytes via suppression of c-Abl activity that was essential for the differentiation of monocytes to fibrocytes. CONCLUSIONS: Imatinib prevents airway luminal obstruction by inhibiting the migration and differentiation of fibrocytes. Fibrocytes may be a novel target in the prevention and treatment of BO. PMID- 27388854 TI - Education a la carte. PMID- 27388853 TI - Burden of advanced breast cancer for patients and caregivers in Europe: comparison of two treatment forms of vinorelbine, oral and intravenous. AB - AIM: To assess the burden of disease associated with advanced breast cancer (ABC) treated with oral (VinO) or intravenous vinorelbine (VinIV) from the perspective of patients and caregivers in five European countries. METHODS: This was an observational, prospective, international, multicenter study. Patients were included in the study at the beginning of their second cycle of chemotherapy with vinorelbine and categorized into two groups depending on whether they received VinO or VinIV. At baseline (V0) and at the end of the second cycle of chemotherapy (V1), patients and caregivers were asked to complete self administered questionnaires: SF-12 and burden of disease. RESULTS: At baseline, the two groups were well balanced in demographic and clinical characteristics. However, while HER2+ (human epidermal growth factor receptor 2) disease was significantly more frequent in patients receiving VinIV, patients receiving VinO were predominantly treated with single-agent therapy and were older than those treated with VinIV (67.1 years versus 57.7 years [p = 0.05]). As measured with SF 12, patients with VinO had, at end of cycle 1 and end of cycle 2, significantly more favorable outcomes in physical summary score, role physical, role emotional and mental health (all p < 0.05) than those treated with VinIV. Trends for a better caregiver mental score and social functioning were also observed with VinO (cycle 1 and 2; p < 0.10). From a patient perspective, no major difference was reported on the burden of disease between the two groups, however, a trend for a better" overall impact on daily life" was observed in VinO patients. Major significant differences, showing a lower burden of disease with VinO, were also reported from caregivers. In addition, in patients treated with VinO, mental score was almost similar to the one of the general population. CONCLUSION: VinO showed benefits over VinIV for both patients and caregivers, particularly in health related quality of life and burden of disease. Because of its observational design, results are only informative. PMID- 27388855 TI - Quote ... unquote. PMID- 27388856 TI - De novo discovery of neuropeptides in the genomes of parasitic flatworms using a novel comparative approach. AB - Neuropeptide mediated signalling is an ancient mechanism found in almost all animals and has been proposed as a promising target for the development of novel drugs against helminths. However, identification of neuropeptides from genomic data is challenging, and knowledge of the neuropeptide complement of parasitic flatworms is still fragmentary. In this work, we have developed an evolution based strategy for the de novo discovery of neuropeptide precursors, based on the detection of localised sequence conservation between possible prohormone convertase cleavage sites. The method detected known neuropeptide precursors with good precision and specificity in the models Drosophila melanogaster and Caenorhabditis elegans. Furthermore, it identified novel putative neuropeptide precursors in nematodes, including the first description of allatotropin homologues in this phylum. Our search for neuropeptide precursors in the genomes of parasitic flatworms resulted in the description of 34 conserved neuropeptide precursor families, including 13 new ones, and of hundreds of new homologues of known neuropeptide precursor families. Most neuropeptide precursor families show a wide phylogenetic distribution among parasitic flatworms and show little similarity to neuropeptide precursors of other bilaterian animals. However, we could also find orthologs of some conserved bilaterian neuropeptides including pyrokinin, crustacean cardioactive peptide, myomodulin, neuropeptide-Y, neuropeptide KY and SIF-amide. Finally, we determined the expression patterns of seven putative neuropeptide precursor genes in the protoscolex of Echinococcus multilocularis. All genes were expressed in the nervous system with different patterns, indicating a hidden complexity of peptidergic signalling in cestodes. PMID- 27388858 TI - A full-potential approach to the relativistic single-site Green's function. AB - One major purpose of studying the single-site scattering problem is to obtain the scattering matrices and differential equation solutions indispensable to multiple scattering theory (MST) calculations. On the other hand, the single-site scattering itself is also appealing because it reveals the physical environment experienced by electrons around the scattering center. In this paper we demonstrate a new formalism to calculate the relativistic full-potential single site Green's function. We implement this method to calculate the single-site density of states and electron charge densities. The code is rigorously tested and with the help of Krein's theorem, the relativistic effects and full potential effects in group V elements and noble metals are thoroughly investigated. PMID- 27388857 TI - Dcsbis (PA2771) from Pseudomonas aeruginosa is a highly active diguanylate cyclase with unique activity regulation. AB - C-di-GMP (3',5' -Cyclic diguanylic acid) is an important second messenger in bacteria that influences virulence, motility, biofilm formation, and cell division. The level of c-di-GMP in cells is controlled by diguanyl cyclases (DGCs) and phosphodiesterases (PDEs). Here, we report the biochemical functions and crystal structure of the potential diguanylase Dcsbis (PA2771, a diguanylate cyclase with a self-blocked I-site) from Pseudomonas aeruginosa PAO1. The full length Dcsbis protein contains an N-terminal GAF domain and a C-terminal GGDEF domain. We showed that Dcsbis tightly coordinates cell motility without markedly affecting biofilm formation and is a diguanylate cyclase with a catalytic activity much higher than those of many other DGCs. Unexpectedly, we found that a peptide loop (protecting loop) extending from the GAF domain occupies the conserved inhibition site, thereby largely relieving the product-inhibition effect. A large hydrophobic pocket was observed in the GAF domain, thus suggesting that an unknown upstream signaling molecule may bind to the GAF domain, moving the protecting loop from the I-site and thereby turning off the enzymatic activity. PMID- 27388859 TI - Mastery Learning of Video Laryngoscopy Using the Glidescope in the Emergency Department. AB - INTRODUCTION: According to the Accreditation Council for Graduate Medical Education emergency medicine requirements established before the popularity of video laryngoscopy (VL) use, 35 intubations are necessary for graduation. Our study aimed to establish a mastery-learning model for a skill set very different (VL) from direct laryngoscopy (DL) and to determine the number of attempts needed to achieve mastery with VL. METHODS: With the use of a randomized, controlled crossover study design, two learner groups underwent baseline testing intubating a mannequin using VL. Afterward, the intervention group received a mastery training intervention. After training, learners were required to repeat the procedure until achievement of 100% on the checklist for two consecutive attempts was achieved. After 3 months, both groups returned for retesting, and the control group received the same mastery training as the intervention group. Both groups returned for final testing after another 3 months. RESULTS: The intervention arm had an improvement in performance versus the control arm at 3 months of total time (P < 0.05). Both groups had an improvement within their groups' checklist scores at 3 months after training (P < 0.05), and within the intervention arm, this effect was sustained at 6 months (P < 0.05). There was no significant difference in the mean required attempts to demonstrate mastery (overall, 2.5; intervention, 2.75; control 2.25; P = 0.28). CONCLUSIONS: Simulation-based mastery-learning produces skill enhancement with VL that is resistant to decay across 6 months. Furthermore, although a small number of attempts are needed to achieve mastery, clinical experience did not substitute as a proxy for skill acquisition. This mastery-learning model provides skill sets that are not otherwise obtained in the clinical curriculum in a 3-month period. PMID- 27388860 TI - Multisite Single-Blinded Randomized Control Study of Transfer and Retention of Knowledge and Skill Between Nurses Using Simulation and Online Self-Study Module. AB - INTRODUCTION: Obstetric (OB) nurses must be proficient in performing a basic neurologic examination to assess and detect changes in a patients' neurologic status. This study aimed to compare knowledge and skill acquisition for a basic neurologic examination between OB nurses who participated in simulation and those who participated in an online self-study module. Short- and long-term knowledge retention and skill transfer between groups were evaluated. METHODS: Nurses were randomized to either simulation or online self-study module and assessed by direct observation and completion of a standardized instrument by the observer at 3 time points: baseline (time 1), within 7 days of baseline in the clinical setting (time 2), and at 2 months (time 3) using a validated12-item Neurologic Knowledge Assessment and a 14-item performance skill checklist. RESULTS: Among OB nurses, those in the simulation group demonstrated higher levels in both short term (time 2) [mean (SD), 67.6 (20.2) vs. 29.6 (19.0); P < 0.001] and long-term (time 3) [mean (SD), 46.1 (17.6) vs. 27.5 (15.9); P < 0.001] skill performance compared with nurses in the online self-study module. Nurses in the simulation and online self-study module groups had similar mean levels on Neurologic Knowledge Assessment scores at time 2 (P = 0.86) and time 3 (P = 0.59), but these mean scores were not significant. CONCLUSIONS: The greater transfer of skills by nurses who received simulation education is an important finding because few studies have addressed this level of translation with practicing nurses. There was a lack of differences in short- and long-term knowledge acquisition between nurses in the simulation and online self-study module groups. More research is needed to determine the timing of simulation-based education repetition over time to aid in knowledge and skills retention. PMID- 27388861 TI - An Approach to Confederate Training Within the Context of Simulation-Based Research. AB - STATEMENT: Simulation-based education often relies on confederates, who provide information or perform clinical tasks during simulation scenarios, to play roles. Although there is experience with confederates in their more routine performance within educational programs, there is little literature on the training of confederates in the context of simulation-based research. The CPR CARES multicenter research study design included 2 confederate roles, in which confederates' behavior was tightly scripted to avoid confounding primary outcome measures. In this report, we describe our training process, our method of adherence assessment, and suggest next steps regarding confederate training scholarship. PMID- 27388862 TI - Preparation With Web-Based Observational Practice Improves Efficiency of Simulation-Based Mastery Learning. AB - INTRODUCTION: Our current understanding of what results in effective simulation based training is restricted to the physical practice and debriefing stages, with little attention paid to the earliest stage: how learners are prepared for these experiences. This study explored the utility of Web-based observational practice (OP) -featuring combinations of reading materials (RMs), OP, and collaboration- to prepare novice medical students for a simulation-based mastery learning (SBML) workshop in central venous catheterization. METHODS: Thirty medical students were randomized into the following 3 groups differing in their preparatory materials for a SBML workshop in central venous catheterization: a control group with RMs only, a group with Web-based groups including individual OP, and collaborative OP (COP) groups in addition to RM. Preparation occurred 1 week before the SBML workshop, followed by a retention test 1-week afterward. The impact on the learning efficiency was measured by time to completion (TTC) of the SBML workshop. Web site preparation behavior data were also collected. RESULTS: Web based groups demonstrated significantly lower TTC when compared with the RM group, (P = 0.038, d = 0.74). Although no differences were found between any group performances at retention, the COP group spent significantly more time and produced more elaborate answers, than the OP group on an OP activity during preparation. DISCUSSION: When preparing for SBML, Web-based OP is superior to reading materials alone; however, COP may be an important motivational factor to increase learner engagement with instructional materials. Taken together, Web based preparation and, specifically, OP may be an important consideration in optimizing simulation instructional design. PMID- 27388863 TI - How Do Simulated Error Experiences Impact Attitudes Related to Error Prevention? AB - INTRODUCTION: The objective of this project was to determine whether simulated exposure to error situations changes attitudes in a way that may have a positive impact on error prevention behaviors. METHODS: Using a stratified quasi randomized experiment design, we compared risk perception attitudes of a control group of nursing students who received standard error education (reviewed medication error content and watched movies about error experiences) to an experimental group of students who reviewed medication error content and participated in simulated error experiences. Dependent measures included perceived memorability of the educational experience, perceived frequency of errors, and perceived caution with respect to preventing errors. RESULTS: Experienced nursing students perceived the simulated error experiences to be more memorable than movies. Less experienced students perceived both simulated error experiences and movies to be highly memorable. After the intervention, compared with movie participants, simulation participants believed errors occurred more frequently. Both types of education increased the participants' intentions to be more cautious and reported caution remained higher than baseline for medication errors 6 months after the intervention. CONCLUSIONS: This study provides limited evidence of an advantage of simulation over watching movies describing actual errors with respect to manipulating attitudes related to error prevention. Both interventions resulted in long-term impacts on perceived caution in medication administration. Simulated error experiences made participants more aware of how easily errors can occur, and the movie education made participants more aware of the devastating consequences of errors. PMID- 27388864 TI - Simulated Disaster Day: Benefit From Lessons Learned Through Years of Transformation From Silos to Interprofessional Education. AB - STATEMENT: Disaster Day is a simulation event that began in the College of Nursing and has increased exponentially in size and popularity for the last 8 years. The evolution has been the direct result of reflective practice and dedicated leadership in the form of students, faculty, and administration. Its development and expansion into a robust interprofessional education activity are noteworthy because it gives health care professions students an opportunity to work in teams to provide care in a disaster setting. The "authentic" learning situation has enhanced student knowledge of roles and responsibilities and seems to increase collaborative efforts with other disciplines. The lessons learned and modifications made in our Disaster Day planning, implementation, and evaluation processes are shared in an effort to facilitate best practices for other institutions interested in a similar activity. PMID- 27388865 TI - The Role of Ultrasound Simulation in Obstetrics and Gynecology Training: A UK Trainees' Perspective. AB - INTRODUCTION: Ultrasonography is a core skill required by all obstetrics and gynecology trainees; however, training opportunities in clinical ultrasound are declining. Simulation ultrasound training has been proposed as a strategy to overcome this.The study aims were to determine the current availability of clinical and simulation ultrasound training in obstetrics and gynecology in the United Kingdom and to explore the trainees' perspective on the role of ultrasound simulation. METHODS: All obstetrics and gynecology trainees within the East Midlands Local Education Training Board in the United Kingdom were asked to complete an anonymous web-based survey in July 2014. RESULTS: Of 140 trainees, 70 (50%) responded to the survey, and 69% reported rarely having dedicated clinical ultrasound sessions. Fifty percent had failed to achieve ultrasound competencies required for their stage of training, and 83% felt that the pressures of service provision limited their exposure to clinical ultrasound.Seventy-three percent of the trainees considered ultrasound simulation to be an essential component of training, and 69% agreed that it would help improve their clinical skills. Only 50% had access to an ultrasound simulator. Seventy-seven percent of the trainees thought that it would be useful to have ultrasound simulation integrated into training. CONCLUSIONS: Trainees are struggling to achieve minimal ultrasound competences with clinical ultrasound training alone. They believe that ultrasound simulation will shorten the learning curve and improve their clinical skills and knowledge. Despite the cost implications of simulation training, we propose that consideration is given to formal integration of ultrasound simulation into the curriculum as a possible way forward. PMID- 27388866 TI - Coaching From the Sidelines: Examining the Impact of Teledebriefing in Simulation Based Training. AB - INTRODUCTION: Although simulation facilities are available at most teaching institutions, the number of qualified instructors and/or content experts that facilitate postsimulation debriefing is inadequate at many institutions. There remains a paucity of evidence-based data regarding several aspects of debriefing, including debriefing with a facilitator present versus teledebriefing, in which participants undergo debriefing with a facilitator providing instruction and direction from an off-site location while they observe the simulation in real time. We conducted this study to identify the effectiveness and feasibility of teledebriefing as an alternative form of instruction. METHODS: This study was conducted with emergency medicine residents randomized into either a teledebriefing or on-site debriefing group during 11 simulation training sessions implemented for a 9-month period. The primary outcome of interest was resident perception of debriefing effectiveness, as measured by the Debriefing Assessment for Simulation in Healthcare-Student Version (See Appendix, Supplemental Digital Content 1, http://links.lww.com/SIH/A282) completed at the end of every simulation session. RESULTS: A total of 44 debriefings occurred during the study period with a total number of 246 Debriefing Assessment for Simulation in Healthcare-Student Version completed. The data revealed a statistically significant difference between the effectiveness of on-site debriefing [6.64 (0.45)] and teledebriefing [6.08 (0.57), P < 0.001]. Residents regularly evaluated both traditional debriefing and teledebriefing as "consistently effective/very good." CONCLUSIONS: Teledebriefing was found to be rated lower than in-person debriefing but was still consistently effective. Further research is necessary to evaluate the effectiveness of teledebriefing in comparison with other alternatives. Teledebriefing potentially provides an alternative form of instruction within simulation environments for programs lacking access to expert faculty. PMID- 27388867 TI - [Supporting, Demanding, and Excessively Demanding?]. PMID- 27388868 TI - [Psychosocial Situation and Patient Satisfaction among Clients of Cancer Counselling Centers in Saxony]. AB - Outpatient psychosocial counselling (OPC) centers for those affected by cancer fulfill 2 main purposes: (a) to offer low-threshold psychological, social and legal counselling, and (b) to refer clients to other services. Here we report findings from a user-based assessment of OPC in the state of Saxony, Germany. This study was funded in part by the Saxon State Ministry of Social Affairs and Consumer Protection. We used a paper-based questionnaire to survey 213 clients of OPC in Saxony at 2 points (t1: up to one week after first contact, t2: 4 months after t1). All participants were cancer patients. The survey assessed utilization of services, depressive symptoms (PHQ-9), anxiety (GAD-7), quality of life (SF-8) as well as clients' satisfaction with the counselling service (ZUF-8). The majority of clients (81%) were referred to the OPC from a hospital or rehabilitation center. 46% of patients only had one contact. 78% of counselling sessions treated matters of social law. Patients suffered from 13 problems on average, the most common being fatigue and exhaustion, worries, anxiety, uncertainty about the future, and pain. Half the patients (49%) reported moderate to severe anxiety and 68% showed elevated levels of depressive symptoms. Psychosocial distress did not change significantly over time (GAD-7: p=0.580, PHQ 9: p=0.101). Patients' quality of life was low overall (cut-off<50). At t2, quality of life had particularly increased in physical aspects, but overall quality of life remained lower than in the general population (all subscales: p<0.05). We identified younger age and lower income as risk factors for higher psychosocial distress and lower quality of life. Patients were very satisfied with the counselling they received, 9% reported to be dissatisfied. Our results show that psychosocial distress remains high over a longer period of time at least for some patients. This illustrates the persisting need for long-term support regarding physical, mental and social impairments as a consequence of cancer and its treatments. It also shows the challenging demands which OPC centers are faced with. As a consequence, psychosocial support in the outpatient setting needs to be extended and developed further. PMID- 27388869 TI - [Schematherapy in Eating Disorders - An Integrative Approach to Improve the Outcome]. AB - Despite evidence-based psychotherapeutic treatment approaches such as cognitive behavioral therapy and psychodynamic therapy eating disorders still pose a challenge to therapists and patients alike. Eating disorders are associated with a high comorbid prevalence of personality disorders and other psychological axis I-disorders, show highdrop-out rates and relapse rates and anorexia nervosa has the highest mortality rate compared to all psychiatric disorders. Even self motivated patients frequently fail to achieve the treatment goals like developing a normal eating behavior, gaining weight, and changing the underlying dysfunctional behavioral patterns and cognitions. We will present a schematherapeutic approach with experiential methods, integrated in evidence based CBT, with the intention to improve motivation and therapeutic outcome. PMID- 27388870 TI - [Use of Monetary Incentives in Face-to-Face Surveys in Light of Decreasing Response Rates]. PMID- 27388871 TI - [Skills Training for Patients with Borderline Personality Disorder]. AB - The emotionally instable personality disorder, mostly called borderline disorder, shows central abnormalities in impulse control as well as instability of mood and identity. It is composed of behaviour problems in creating relationships and in self-management, first of all by high psychophysiological tension. The prevalence of this disorder is 10 % in outpatients and 20 % in inpatients and has therefore high relevance for the medical-psychotherapeutic care system. The treatment is deemed to be complex and interminable. Regarding all evaluated techniques of treatment the best examined is the Dialectical Behavioral Therapy (DBT). This specific therapy, developed in the eighties by Marsha M. Linehan, can be used for inpatient and outpatient treatment and combines single and group sessions. It is essential in mental health care of this disorder, but not available everywhere. Essential part of DBT is the skill training, a specific technique for the acquirement and for exercising skills for mindfulness, modulation of tension, regulation of emotions, structuring of social competence and developing self value. The central goal of DBT is to ensure the survival of the patients, to reduce self- and external aggressive behaviour and to provide inpatient crisis interventions. For sustained crisis management skills for reality acceptance are best fitting. But before, fast available sensory and active body-related skills should be used. Radical acceptance is the most important, since most effective, skill. The skills training, although in use for only twenty years, is permanently expanding in practice and is meanwhile also used for other disorders such as, for example, PTSD or ADHD. Since 2010, there also exists an elaborated DBT-version for adolescents. For medical care politics and health-economic reasons a supply with skills training for in- and outpatients all over the country is desirable. PMID- 27388872 TI - TRIM5 gene polymorphisms in HIV-1-infected patients and healthy controls from Northeastern Brazil. AB - Humans show heterogeneity in vulnerability to HIV-1 infection, partially under control of genes involved in host immunity and virus replication. TRIM5alpha protein has restriction activity against replication of many retroviruses. Human TRIM5 gene single nucleotide polymorphisms have been reported as involved in susceptibility to HIV-1 infection. We recruited 213 HIV-1-positive patients and 234 healthy uninfected controls from Northeast Brazil; two non-synonymous variants at exon 2, rs3740996 (H43Y) and rs10838525 (R136Q), and one regulatory polymorphism (rs16934386) at 5'UTR region of TRIM5 were analyzed. The R136Q variation presented significant differences between HIV-1-positive patients and healthy controls. The 136Q allele and the 136QQ genotype were more frequent in healthy controls (32.7 and 10.2 %, respectively) than in HIV-1-positive patients (136Q allele: 24.4 %; OR 0.66; CI 95 % 0.49-0.90; p value = 0.008/136QQ genotype: 4.2 %; OR 0.33; CI 95 % 0.13-0.79, p = 0.008) also after adjusting for age and sex. We also stratified our findings according to the presence of CCR5Delta32 variation, but the results remained the same. We observed that rs10838525 (R136Q) and rs3740996 (H43Y) were in linkage disequilibrium (D' = 0.71), forming four possible haplotypes. The H43-136Q haplotype was significantly more frequent in healthy controls (28.2 %) than in HIV-positive patients (21.4 %; OR 0.69; CI 95 % 0.50-0.96; p = 0.022). An increased frequency of allele (136Q) and genotype (136QQ) of the non-synonymous rs10838525 (R136Q) variant and the haplotype (43H 136Q) was observed among healthy controls individuals. Being aware of the limitation of this study (unavailability of exposed but uninfected individuals), we hypothesize a potential role for TRIM5 variations in the protection against HIV-1 infection. PMID- 27388874 TI - Effect of Fingolimod-Treatment on Blood Lipid Profiles of Multiple Sclerosis Patients. PMID- 27388873 TI - The health and economic benefits of the global programme to eliminate lymphatic filariasis (2000-2014). AB - BACKGROUND: Lymphatic filariasis (LF), also known as elephantiasis, is a neglected tropical disease (NTD) targeted for elimination through a Global Programme to Eliminate LF (GPELF). Between 2000 and 2014, the GPELF has delivered 5.6 billion treatments to over 763 million people. Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF. METHOD: We combined previously established models to estimate the number of clinical manifestations and disability-adjusted life years (DALYs) averted from three benefit cohorts (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The economic savings associated with this disease prevention was then analysed in the context of prevented medical expenses incurred by LF clinical patients, potential income loss through lost-labour, and prevented costs to the health system to care for affected individuals. The indirect cost estimates were calculated using the human capital approach. A combination of four wage sources was used to estimate the fair market value of time for an agricultural worker with LF infection (to ensure a conservative estimate, the lowest wage value was used). RESULTS: We projected that due to the first 15 years of the GPELF 36 million clinical cases and 175 (116-250) million DALYs will potentially be averted. It was estimated that due to this notable health impact, US$100.5 billion will potentially be saved over the lifetimes of the benefit cohorts. This total amount results from summing the medical expenses incurred by LF patients (US$3 billion), potential income loss (US$94 billion), and costs to the health system (US$3.5 billion) that were projected to be prevented. The results were subjected to sensitivity analysis and were most sensitive to the assumed percentage of work hours lost for those suffering from chronic disease (changing the total economic benefit between US$69.30-150.7 billion). CONCLUSIONS: Despite the limitations of any such analysis, this study identifies substantial health and economic benefits that have resulted from the first 15 years of the GPELF, and it highlights the value and importance of continued investment in the GPELF. PMID- 27388875 TI - The Naive Utility Calculus: Computational Principles Underlying Commonsense Psychology. AB - We propose that human social cognition is structured around a basic understanding of ourselves and others as intuitive utility maximizers: from a young age, humans implicitly assume that agents choose goals and actions to maximize the rewards they expect to obtain relative to the costs they expect to incur. This 'naive utility calculus' allows both children and adults observe the behavior of others and infer their beliefs and desires, their longer-term knowledge and preferences, and even their character: who is knowledgeable or competent, who is praiseworthy or blameworthy, who is friendly, indifferent, or an enemy. We review studies providing support for the naive utility calculus, and we show how it captures much of the rich social reasoning humans engage in from infancy. PMID- 27388876 TI - Methodological Considerations to Strengthen Studies of Peripheral Vision. AB - In a recent issue of Trends in Cognitive Sciences, Cohen et al.[1] argue that the study of visual summary statistics represents an elegant method to account for the richness of visual experience in the periphery. We resoundingly agree that employing ensemble statistics is a strong step towards resolving questions of how conscious we are of our visual surroundings. However, we think the explanatory power of this approach can be augmented by focusing on two specific areas: (i) psychophysical quantification of metacognitive capacities and decision biases associated with peripheral vision; (ii) distinction between perceptual decisions that involve different levels of detail. Consideration of these issues will facilitate the development of precise hypotheses about peripheral phenomenology and yield useful data from experiments investigating summary statistics; we explain how below. PMID- 27388877 TI - Using automatically extracted information from mammography reports for decision support. AB - OBJECTIVE: To evaluate a system we developed that connects natural language processing (NLP) for information extraction from narrative text mammography reports with a Bayesian network for decision-support about breast cancer diagnosis. The ultimate goal of this system is to provide decision support as part of the workflow of producing the radiology report. MATERIALS AND METHODS: We built a system that uses an NLP information extraction system (which extract BI RADS descriptors and clinical information from mammography reports) to provide the necessary inputs to a Bayesian network (BN) decision support system (DSS) that estimates lesion malignancy from BI-RADS descriptors. We used this integrated system to predict diagnosis of breast cancer from radiology text reports and evaluated it with a reference standard of 300 mammography reports. We collected two different outputs from the DSS: (1) the probability of malignancy and (2) the BI-RADS final assessment category. Since NLP may produce imperfect inputs to the DSS, we compared the difference between using perfect ("reference standard") structured inputs to the DSS ("RS-DSS") vs NLP-derived inputs ("NLP DSS") on the output of the DSS using the concordance correlation coefficient. We measured the classification accuracy of the BI-RADS final assessment category when using NLP-DSS, compared with the ground truth category established by the radiologist. RESULTS: The NLP-DSS and RS-DSS had closely matched probabilities, with a mean paired difference of 0.004+/-0.025. The concordance correlation of these paired measures was 0.95. The accuracy of the NLP-DSS to predict the correct BI-RADS final assessment category was 97.58%. CONCLUSION: The accuracy of the information extracted from mammography reports using the NLP system was sufficient to provide accurate DSS results. We believe our system could ultimately reduce the variation in practice in mammography related to assessment of malignant lesions and improve management decisions. PMID- 27388879 TI - Assessing the impact of nocturia on health-related quality-of-life and utility: results of an observational survey in adults. AB - BACKGROUND AND AIM: The impact of nocturia (getting up at night to void) on health-related quality-of-life (HRQoL) is often under-estimated. This study investigated the relative burden in terms of HRQoL and utilities of nocturia in a real-world setting. METHODS: Patient data were collected from two surveys: a nocturia-specific, cross-sectional survey of physicians and their patients (DSP), and a general UK population health survey (HSFE). Utilities (EQ-5D-5L), productivity (Work Productivity and Activity Index), and the impact of nocturia symptoms (Nocturia Impact Diary and Overactive Bladder Questionnaires) were assessed against the number of voids. A robust linear regression model with propensity score weights was used to control for confounding factors in estimating utilities. RESULTS: Physician-recorded data were available from 8,738 patients across the US, Germany, Spain, France, and the UK; of these, 5,335 (61%) included patient-reported outcomes. In total, 6,302 controls were drawn from the two surveys and compared to 1,104 nocturia patients. Deterioration of HRQoL was associated with increasing number of night-time voids (p < 0.0001). In particular, significant differences were observed between 0-1 and >=2 voids (p < 0.001). The regression model demonstrated that nocturia (>=2 per night) is associated with a modest but significant deterioration in utility of 0.0134 (p < 0.05). LIMITATIONS: The cause of nocturia is multifactorial and the mostly elderly patients may have several concomitant diseases. The authors tried to adjust for the most common ones, but there may be diseases or unknown relationships not included. CONCLUSIONS: Nocturia negatively affected HRQoL and patient utility. A clear effect is seen already at two voids per night. Every effort should, therefore, be made to reduce nocturia below the bother threshold of two voids per night. PMID- 27388878 TI - Effectiveness and cost-effectiveness of a self-management training for patients with chronic and treatment resistant anxiety or depressive disorders: design of a multicenter randomized controlled trial. AB - BACKGROUND: Many patients with anxiety or depressive disorders achieve no remission of their symptoms after evidence-based treatment algorithms. They develop a chronic course of the disorder. Current care for these patients usually consists of long-term supportive contacts with a community psychiatric nurse and pharmacological management by a psychiatrist. Data on the effectiveness of these treatments is lacking. A psychosocial rehabilitation approach, where self management is an increasingly important part, could be more suitable. It focuses on the restoration of functioning and enhancement of patients' autonomy and responsibility. Treatment with this focus, followed by referral to primary care, may be more (cost-)effective. METHODS: A multicenter randomized controlled trial is designed for twelve participating specialized outpatient mental health services in the Netherlands. Patients with chronic and treatment resistant anxiety or depressive disorders, currently receiving supportive care in specialized outpatient mental health care, are asked to participate. After inclusion, patients receive the baseline questionnaire and are randomized to the intervention group or the usual care control group. The intervention focuses on rehabilitation and self-management and is provided by a trained community psychiatric nurse, followed by referral to primary care. Measurements take place at 6, 12, and 18 months after baseline. This study evaluates both the effectiveness (on quality of life, symptom severity, and empowerment), and cost effectiveness of the intervention compared to usual care. In addition, a questionnaire is designed to get insight in which self-management strategies patients use to manage their disorder, and in the experiences of patients with the change of care setting. DISCUSSION: In this study we evaluate the effectiveness and cost-effectiveness of a self-management intervention for patients with chronic and treatment resistant anxiety or depressive disorders in specialized outpatient mental health care. The results of this study may provide a first 'proof-of-concept' in this under-researched but important field, and might be relevant for a large group of patients in the context of a transition of the Dutch health care system. TRIAL REGISTRATION: Netherlands Trial Register: NTR3335 , registered 7 March 2012. PMID- 27388880 TI - Halofuginone Alleviates Burn-Induced Hepatic and Renal Damage in Rats. AB - The aim of this study was to evaluate the possible protective effects of halofuginone on burn-induced oxidative injury of the liver and kidney. For the induction of burn, backs of Wistar albino rats were shaved and exposed for 10 seconds to water bath at 90 degrees C, whereas rats in the control group were exposed for 10 seconds at 25 degrees C. Rats were then administered either saline (1 ml/kg) or halofuginone (100 MUg/kg/day) intraperitoneally and decapitated at the 24th hour (early burn) or on the 7th day (late burn). Serum concentrations of creatinine, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase were determined. Renal and hepatic tissue samples were used for microscopic analysis, and glutathione, malondialdehyde, and myeloperoxidase activity and chemiluminescence levels were measured. Halofuginone treatment improved renal functions in late burn group and hepatic functions in early burn group as demonstrated by decreased serum creatinine, blood urea nitrogen, and alanine aminotransferase levels. Increased serum lactate dehydrogenase level measured in late phase was reduced by halofuginone treatment. Generation of reactive oxygen metabolites measured by chemiluminescence, indicating burn induced renal and hepatic oxidative injury in both the early and late burn groups, was reduced by halofuginone. Increased hepatic malondialdehyde levels accompanied with high microscopic damage scores were reversed by halofuginone in early burn group, while depleted renal glutathione levels were replenished. The present findings demonstrate that halofuginone preserved renal and hepatic functions and alleviated oxidative tissue damage insulted by burn trauma, suggesting an anti-inflammatory and antioxidant potential for halofuginone in providing protection against burn-induced renal and hepatic injury. PMID- 27388881 TI - Psychometric Properties of the Modified 5-D Itch Scale in a Burn Model System Sample of People With Burn Injury. AB - The aim of this study is to evaluate the psychometric properties of the 4 dimension (4-D) itch scale, a modified version of the 5-dimension itch scale, in a sample of individuals with severe burn injury and/or burn injuries to hands, face, and/or feet. Four of the five domains of the 5-dimension itch scale (4-D) were administered to individuals who reported itching (N = 173) in the Burn Injury Model System Centers Program longitudinal study at either 5 or 10 years after injury. Analyses of the scale included evaluation of dimensionality, internal consistency, associations with other symptoms or quality of life measures, and an examination of floor and ceiling effects. Fit values from a one factor confirmatory factor analysis were acceptable, supporting unidimensionality. Cronbach's alpha was 0.82, indicating good internal consistency. One item had a corrected item-total score correlation of less than 0.40. Associations between the 4-D and other measures were in the expected direction and magnitude. A negligible number of participants (no more than two) selected the lowest category for all items (ie, minimal floor effect) or the highest category for all items (ie, minimal ceiling effect). 4-D had acceptable psychometric properties in a sample of adult burn injury survivors; however, the scale could be improved by removing the item with a low correlation with the total score. PMID- 27388882 TI - Postoperative Delirium in Severely Burned Patients Undergoing Early Escharotomy: Incidence, Risk Factors, and Outcomes. AB - The aim of this study is to investigate the incidence, related risk factors, and outcomes of postoperative delirium (POD) in severely burned patients undergoing early escharotomy. This study included 385 severely burned patients (injured <1 week; TBSA, 31-50% or 11-20%; American Society of Anesthesiologists physical status, II-IV) aged 18 to 65 years, who underwent early escharotomy between October 2014 and December 2015, and were selected by cluster sampling. The authors excluded patients with preoperative delirium or diagnosed dementia, depression, or cognitive dysfunction. Preoperative, perioperative, intraoperative, and postoperative information, such as demographic characteristics, vital signs, and health history were collected. The Confusion Assessment Method was used once daily for 5 days after surgery to identify POD. Stepwise binary logistic regression analysis was used to identify the risk factors for POD, t-tests, and chi tests were performed to compare the outcomes of patients with and without the condition. Fifty-six (14.55%) of the patients in the sample were diagnosed with POD. Stepwise binary logistic regression showed that the significant risk factors for POD in severely burned patients undergoing early escharotomy were advanced age (>50 years old), a history of alcohol consumption (>3/week), high American Society of Anesthesiologists classification (III or IV), time between injury and surgery (>2 days), number of previous escharotomies (>2), combined intravenous and inhalation anesthesia, no bispectral index applied, long duration surgery (>180 min), and intraoperative hypotension (mean arterial pressure < 55 mm Hg). On the basis of the different odds ratios, the authors established a weighted model. When the score of a patient's weighted odds ratios is more than 6, the incidence of POD increased significantly (P < .05). When the score of a patient's weighted odds ratios is more than 6, the incidence of POD increased significantly (P < .05). Further, POD was associated with more postoperative complications, including hepatic and renal function impairment and hypernatremia, as well as prolonged hospitalization, increased medical costs, and higher mortality. PMID- 27388884 TI - District of Columbia Emergency Healthcare Coalition Burn Mass Casualty Plan: Development to Exercise Date. AB - The District of Columbia Emergency Healthcare Coalition (DC EHC) brought together a Burn Task Force to tackle the issue of mass burn care in a metropolitan area in light of limited local burn center resources. This article outlines the development of the mass burn care plan. Using a tiered treatment approach, mass burn victims would be transported first to burn centers within the area, followed by nonburn center trauma centers, and finally to nonburn and nontrauma center acute care facilities. Once activated the Burn Task Force would triage and coordinate transfer of mass burn patients within the District for further care at burn centers using a strong link with the Eastern Regional Burn Disaster Consortium. This plan was exercised in the spring of 2014 to test all of the components. To strengthen mass burn care, this plan, put in place for the District of Columbia, has been expanded to include the National Capital Region as well. PMID- 27388883 TI - Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury. AB - Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, the authors examined whether therapeutic intervention with mesalamine (5-aminosalicylic acid [5-ASA]), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an approximately 20% TBSA dorsal scald burn and resuscitated with either 1 ml normal saline or 100 mg/kg of 5-ASA dissolved in saline. The authors examined intestinal transit and permeability along with the levels of small intestine epithelial cell proinflammatory cytokines and tight junction protein expression 1 day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed 1 day after burn injury, which accompanied a significant increase in gut permeability. The authors found a substantial increase in the levels of interleukin (IL)-6 (by ~1.5-fold) and IL-18 (by ~2.5-fold) in the small intestine epithelial cells 1 day after injury. Furthermore, burn injury decreases the expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn-induced increase in permeability, partially restored normal intestinal transit, normalized the levels of the proinflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin compared with that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury. PMID- 27388885 TI - Inaccuracy of Urine Output Measurements due to Urinary Retention in Catheterized Patients in the Burn ICU. AB - Electronic urinary output monitors, intended to provide urine output information to guide fluid therapy during burn resuscitation, can be inaccurate because of airlocks causing urine retention in the drainage tube and bladder. In this study, the authors explore the effects of airlock formation on urine output measured using an electronic urinary output monitor connected to either a standard commercial drainage tubing system or a drainage tubing system with an automated airlock clearing mechanism. In a multicenter study in the burn intensive care unit, urine output was compared between 10 control patients with a standard commercial drainage tubing system and 10 test patients with a novel automated airlock clearing drainage tubing system. The comparison was focused on identifying the number and magnitude of surges in urinary output because of airlocks and associated periods of false oliguria. In the control group, 5 of 10 (50%) patients had drainage line flow impediments from 8 airlocks. In addition, control patients experienced six associated periods of false oliguria. Airlock surge volumes ranged from 50 to 329 ml, and false oliguria duration ranged from 39.4 to 185.2 minutes. In the test group, 0 of 10 (0%) patients had drainage line impediments from airlocks (P < .01), and hence, there were no periods of false oliguria. Airlocks and associated periods of false oliguria occur with standard commercial drainage tubing and are eliminated using an automated airlock clearing drainage tube. Electronic urinary output monitoring with self-clearing drainage has the potential to improve tracking of real-time urine output and decrease caregiver workload. PMID- 27388886 TI - Measuring Depression in Adults With Burn Injury: A Systematic Review. AB - We conducted a systematic review of the literature to identify evidence to support the use of measures of depression for adults with burn injuries. Our goal was to be able to identify the most reliable, valid, and efficient means of identifying adults with symptoms of depression including major depressive disorder. We modified established guidelines for conducting systematic reviews by excluding measures that focused on distress or anxiety or only used depression as a predictor of interest. We also excluded studies that did not report psychometric data in their results. We identified a total of 213 articles that broadly addressed the topic of depression in burn injuries; of those, 56 that met the majority of the inclusion criteria and used depression as either the primary or the secondary outcome were reviewed. Nine studies that included report of some psychometric properties were reviewed. There have been no measures specifically developed to measure depression in those with burn injuries, and it is unclear if they are actually needed. Greater understanding of depression after burn injury can be gained by evaluating the existing general measures of depression and how they are used in the field of burn injury rehabilitation. The ultimate goal is to develop a set of recommendations for the standardization of how depressive symptomatology is assessed in this population. In this review, we highlight the deficiencies of validated measures of depression in the field of burn recovery and provide specific recommendations for both clinicians and researchers to advance our knowledge of depression following a burn injury, which will allow us to advance treatment. PMID- 27388888 TI - Relationship Between the Remaining Years of Healthy Life Expectancy in Older Age and National Income Level, Educational Attainment, and Improved Water Quality. AB - The remaining years of healthy life expectancy (RYH) at age 65 years can be calculated as RYH (65) = healthy life expectancy-aged 65 years. This study confirms the associations between socioeconomic indicators and the RYH (65) in 148 countries. The RYH data were obtained from the World Health Organization. Significant positive correlations between RYH (65) in men and women and the socioeconomic indicators national income, education level, and improved drinking water were found. Finally, the predictors of RYH (65) in men and women were used to build a model of the RYH using higher socioeconomic indicators (R(2 )= 0.744, p < .001). Overall country-level educational attainment, national income level, and improved water quality influenced the RYH at 65 years. Therefore, policymaking to improve these country-level socioeconomic factors is expected to have latent effects on RYH in older age. PMID- 27388889 TI - A Comparative Study on Retirement Process in Korea, Germany, and the United States: Identifying Determinants of Retirement Process. AB - This study classifies the retirement process and empirically identifies the individual and institutional characteristics determining the retirement process of the aged in South Korea, Germany, and the United States. Using data from the Cross-National Equivalent File, we use a multinomial logistic regression with individual factors, public pension, and an interaction term between an occupation and an education level. We found that in Germany, the elderly with a higher education level were more likely to continue work after retirement with a relatively well-developed social support system, while in Korea, the elderly, with a lower education level in almost all occupation sectors, tended to work off and on after retirement. In the United States, the public pension and the interaction terms have no statistically significant impact on work after retirement. In both Germany and Korea, receiving a higher pension decreased the probability of working after retirement, but the influence of a pension in Korea was much greater than that of Germany. In South Korea, the elderly workers, with lower education levels, tended to work off and on repeatedly because there is no proper security in both the labor market and pension system. PMID- 27388887 TI - Expression of B-class MADS-box genes in response to variations in photoperiod is associated with chasmogamous and cleistogamous flower development in Viola philippica. AB - BACKGROUND: Some plants develop a breeding system that produces both chasmogamous (CH) and cleistogamous (CL) flowers. However, the underlying molecular mechanism remains elusive. RESULTS: In the present study, we observed that Viola philippica develops CH flowers with short daylight, whereas an extended photoperiod induces the formation of intermediate CL and CL flowers. In response to long daylight, the respective number and size of petals and stamens was lower and smaller than those of normally developed CH flowers, and a minimum of 14-h light induced complete CL flowers that had no petals but developed two stamens of reduced fertility. The floral ABC model indicates that B-class MADS-box genes largely influence the development of the affected two-whorl floral organs; therefore, we focused on characterizing these genes in V. philippica to understand this particular developmental transition. Three such genes were isolated and respectively designated as VpTM6-1, VpTM6-2, and VpPI. These were differentially expressed during floral development (particularly in petals and stamens) and the highest level of expression was observed in CH flowers; significantly low levels were detected in intermediate CL flowers, and the lowest level in CL flowers. The observed variations in the levels of expression after floral induction and organogenesis apparently occurred in response to variations in photoperiod. CONCLUSIONS: Therefore, inhibition of the development of petals and stamens might be due to the downregulation of B-class MADS-box gene expression by long daylight, thereby inducing the generation of CL flowers. Our work contributes to the understanding of the adaptive evolutionary formation of dimorphic flowers in plants. PMID- 27388890 TI - Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking? AB - Inflammatory bowel disease (IBD) is characterized by severe gastrointestinal inflammation and results from a complex interplay between genetic and environmental factors. IBD includes two prominent subtypes: Crohn's disease (CD) and ulcerative colitis (UC). One of the main risk factors for the development of CD is cigarette smoking, while UC is rather a disease of ex-smokers. To date, many of the mechanisms underlying the immune imbalance in IBD and the involvement of cigarette smoke (CS) are incompletely understood. Transient receptor potential (TRP) proteins are non-selective cation channels that, upon activation, lead to plasma membrane depolarization and, in general, to Ca2+ influx. TRP channels of the ankyrin and vanilloid family, expressed by sensory neurons in the central and enteric nervous systems, have been extensively studied in the context of intestinal inflammation. Moreover, recent advances made on the role of non neuronal expressed TRP channels shed light on the involvement of epithelial cells in inflammatory processes. This review focuses on how CS may impact TRP channel function in intestinal inflammation. Firstly, we discuss the current knowledge on neuronal TRP channels, known to be linked to IBD, in health, immune homeostasis and intestinal inflammation. Subsequently, we address how TRP channels are activated by CS and its components in other organ systems and also hypothesize on the potential implications for CS-mediated TRP channel activation in gut inflammation. PMID- 27388891 TI - Rare complication of pediatric inguinal hernia repair: case report of transection of the femoral vein. AB - INTRODUCTION: The incidence of pediatric inguinal hernias ranges up to 13 %. Currently, many different techniques are being used to successfully perform herniotomy and risks of complications are minor. CASE REPORT: This case report describes a 4-year-old male patient who underwent routine herniotomy during which the femoral vein was mistaken for hernial sac and thereby the femoral vein was transected. Postoperative vascular duplex ultrasonography revealed a complete transection of the right common femoral vein. Multiple treatment options such as venous reconstruction and interposition were considered, but a conservative treatment was chosen. At 6 months postoperative, the patient only shows minor complaints. Long-term results remain uncertain, especially since no similar case has previously been described in the current literature. PMID- 27388893 TI - Response to: 'Why screening tests to predict injury do not work-and probably never will...: a critical review'. PMID- 27388892 TI - Injury surveillance at 23 International Tennis Federation Junior and Pro Circuit tournaments between 2011 and 2015. PMID- 27388895 TI - Multifunctional upconversion nanoparticles for targeted dual-modal imaging in rat glioma xenograft. AB - PURPOSE: Achieving a radiographic gross total resection in high-grade gliomas improves overall survival. Many technologies such as intraoperative microscope, intraoperative ultrasound, fluorescence imaging, and intraoperative magnetic resonance imaging have been applied to improve tumor resection. However, most commercial available magnetic resonance imaging contrast agents have limited permeability across the blood-brain barrier and are cleared rapidly from circulation. Fluorescence imaging discriminates tumor from normal tissue and provides a promising new strategy to maximize sage surgical resection of tumor. However, the penetration depth of fluorescence imaging is generally low. MATERIALS AND METHODS: In this study, a new type of magnetite NaGdF4:Yb(3+),Er(3+),Li(+)@NaGdF4 (UCNPs) core-shell nanoparticles, coated with SiO2 and further functionalized with glioma and blood-brain barrier targeting motifs, was prepared for dual-modal in vivo upconversion imaging and magnetic resonance imaging. RESULTS: The as-prepared multifunctional upconversion nanoparticles (UCNPs@SiO2-CX-Lf) were biocompatible, showed strong upconversion luminescence under excitation of 980 nm, and provided high signal-to-noise ratio in vivo. Moreover, UCNPs@SiO2-CX-Lf nanoparticles showed a high relaxivity of 1.25 S(-1 )mM(-1) and were successfully applied as contrast agent for magnetic resonance imaging in tumor xenograft rat model with prolonged tumor signal enhancement. In vivo and magnetic resonance imaging Upconversion Luminescence (UCL) imaging results indicated that these particles can across the blood-brain barrier, bind to glioma, gave bright UCL signal and T1 magnetic resonance imaging contrast. CONCLUSIONS: Targeted UCL and magnetic resonance imaging dual-modal in vivo imaging using Yb(3+)/Er(3+)/Li(+) codoped NaGdF4 core-shell nanostructure can serve as a platform technology for the next generation of intraoperative probes for image-guided tumor resection. PMID- 27388894 TI - Occupational prestige, social mobility and the association with lung cancer in men. AB - BACKGROUND: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory. METHODS: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results. RESULTS: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories. CONCLUSIONS: Our results indicate that occupational prestige is independently associated with lung cancer among men. PMID- 27388896 TI - Impacts of decline harvest of country food on nutrient intake among Inuit in Arctic Canada: impact of climate change and possible adaptation plan. AB - BACKGROUND: The pervasive food insecurity and the diet transition away from local, nutrient-rich country foods present a public health challenge among Inuit living in the Canadian Arctic. While environmental factors such as climate change decreased the accessibility and availability of many country food species, new species were introduced into regions where they were previously unavailable. An adaptation such as turning to alternate country food species can be a viable solution to substitute for the nutrients provided by the declined food species. The objective of this study was to estimate the impact on nutrient intake using hypothetical scenarios that current commonly harvested country foods were reduced by 50%, and were replaced with alternate or new species. METHODS: Data collected during the 2007-2008 Inuit Health Survey from 36 Canadian Arctic communities spanning Nunavut, the Inuvialuit Settlement Region and Nunatsiavut were used. RESULTS: A 50% decline in consumption of fish, whale, ringed seals and birds (the food that was reported to be in decline) resulted in a significant decrease in essential nutrient intake. Possible substitute foods were identified but some nutrients such as zinc and especially vitamin D were most often found lacking in the alternative diet. CONCLUSIONS: If the alternative species are not available or feasible, more expensive and less nutritionally dense store-bought foods may be sought. Given the superior quality of country foods and their association with food security, and Inuit cultural health and personal identity, developing skills and awareness for adaptation, promoting regional sharing networks, forming a co management agency and continuing nutritional monitoring may potentially preserve the nutritional integrity of Inuit diet, and in turn their health and cultural survival. PMID- 27388897 TI - Comparison of charges and resource use associated with saxagliptin and sitagliptin. AB - OBJECTIVES: Saxagliptin and sitagliptin are two commonly used dipeptidyl peptidase-4 (DPP-4) inhibitors. Little is known about their comparative effectiveness in the real world, particularly their impact on cost and resources use. The objective of this study was to analyze charges and resource use associated with saxagliptin and sitagliptin to understand the impact of these DPP 4 inhibitor treatment options in a real-world setting. METHODS: This was a retrospective, new-user study approved by the Institutional Review Board at the University of Toledo. Data were collected from a US insurance claims dataset (OptumInsight) for patients newly initiating treatment with saxagliptin or sitagliptin between January 1, 2010 and December 31, 2011. ICD-9 code 250 was used to identify patients with T2D. Overall and diabetes-related medical and pharmacy charges were observed. Inpatient hospitalizations were also compared. Propensity score matching was used to balance the cohorts of patients prescribed saxagliptin and sitagliptin. Appropriate univariate statistical tests were applied to the propensity-matched sample to examine differences in resource utilization outcomes. Statistical significance was evaluated at P < 0.05. RESULT: After the propensity score matching, each cohort included 7711 patients. Saxagliptin treatment was associated with lower overall charges ($13,292 vs $14,032; P = 0.0023) and overall medical charges ($9,540 vs $10,296; P = 0.0024) during the 6-month follow-up period compared with sitagliptin treatment. No significant differences were observed in the overall pharmacy charges ($3,751 vs $3,753; P = 0.6937) and the diabetes-related charges ($5,141 vs $5,232; P = 0.2957). All-cause and diabetes-related inpatient hospitalization rates were significantly lower with saxagliptin treatment (p = 0.0001 and p = 0.0019, respectively). All-caused inpatient charges were also significantly lower with saxagliptin ($2,917.26 vs $3445.89; P < 0.0001). CONCLUSION: Compared with patients initiating sitagliptin treatment, patients initiating saxagliptin treatment reported lower overall and medical charges and lower overall and diabetes-related hospitalization rates. These findings may aid payers in managing patients with T2D. PMID- 27388898 TI - In Vitro Analysis of Predicted DNA-Binding Sites for the Stl Repressor of the Staphylococcus aureus SaPIBov1 Pathogenicity Island. AB - The regulation model of the Staphylococcus aureus pathogenicity island SaPIbov1 transfer was recently reported. The repressor protein Stl obstructs the expression of SaPI proteins Str and Xis, latter which is responsible for mobilization initiation. Upon Phi11 phage infection of S. aureus. phage dUTPase activates the SaPI transfer via Stl-dUTPase complex formation. Our aim was to predict the binding sites for the Stl repressor within the S. aureus pathogenicity island DNA sequence. We found that Stl was capable to bind to three 23-mer oligonucleotides, two of those constituting sequence segments in the stl str, while the other corresponding to sequence segment within the str-xis intergenic region. Within these oligonucleotides, mutational analysis revealed that the predicted binding site for the Stl protein exists as a palindromic segment in both intergenic locations. The palindromes are built as 6-mer repeat sequences involved in Stl binding. The 6-mer repeats are separated by a 5 oligonucleotides long, nonspecific sequence. Future examination of the interaction between Stl and its binding sites in vivo will provide a molecular explanation for the mechanisms of gene repression and gene activation exerted simultaneously by the Stl protein in regulating transfer of the SaPIbov1 pathogenicity island in S. aureus. PMID- 27388900 TI - [Health services access survey for Colombian households]. AB - OBJECTIVE: The aim of this study was to design and validate a health services access survey for households in Colombia to provide a methodological tool that allows the country to accumulate evidence of real-life access conditions experienced by the Colombian population. METHODS: A validation study with experts and a pilot study were performed. It was conducted in the municipality of Jamundi, located in the department of Valle del Cauca, Colombia. Probabilistic, multistage and stratified cluster sampling was carried out. The final sample was 215 households. RESULTS: The survey was composed of 63 questions divided into five modules: socio-demographic profile of the head of the household or adult informant, household socioeconomic profile, access to preventive services, access to curative and rehabilitative services and household out of pocket expenditure. In descriptive terms, the promotion of preventive services only reached 44%; the use of these services was always highest among children younger than one year old and up to the age of ten. The perceived need for emergency medical care and hospitalisation was between 82% and 85%, but 36% perceived the quality of care to be low or very low. Delays were experienced in medical visits with GPs and specialists. DISCUSSION: The designed survey is valid, relevant and representative of access to health services in Colombia. Empirically, the pilot showed institutional weaknesses in a municipality of the country, indicating that health coverage does not in practice mean real and effective access to health services. PMID- 27388899 TI - Adherence to ketoacids/essential amino acids-supplemented low protein diets and new indications for patients with chronic kidney disease. AB - BACKGROUND: Low protein diets (LPD) have long been prescribed to chronic kidney disease patients with the goals of improving metabolic abnormalities and postpone the start of maintenance dialysis. METHODS: We reviewed the recent literature addressing low protein diets supplemented with ketoacids/essential aminoacids prescribed during chronic kidney disease and their effects on metabolic, nutritional and renal parameters since 2013. RESULTS: We show new information on how to improve adherence to these diets, on metabolic improvement and delay of the dialysis needs, and preliminary data in chronic kidney disease associated pregnancy. In addition, data on incremental dialysis have been reviewed, as well as potential strategies to reverse protein energy wasting in patients undergoing maintenance dialysis. CONCLUSION: These recent data help to better identify the use of low protein diets supplemented with ketoacids/essential aminoacids during chronic kidney disease. PMID- 27388902 TI - Development and Validation of an Instrument to Evaluate Perceived Wellbeing Associated with the Ingestion of Water: The Water Ingestion-Related Wellbeing Instrument (WIRWI). AB - BACKGROUND: Ingestion of water has been associated with general wellbeing. When water intake is insufficient, symptoms such as thirst, fatigue and impaired memory result. Currently there are no instruments to assess water consumption associated with wellbeing. The objective of our study was to develop and validate such an instrument in urban, low socioeconomic, adult Mexican population. METHODS: To construct the Water Ingestion-Related Wellbeing Instrument (WIRWI), a qualitative study in which wellbeing related to everyday practices and experiences in water consumption were investigated. To validate the WIRWI a formal, five-process procedure was used. Face and content validation were addressed, consistency was assessed by exploratory and confirmatory psychometric factor analyses, repeatability, reproducibility and concurrent validity were assessed by conducting correlation tests with other measures of wellbeing such as a quality of life instrument, the SF-36, and objective parameters such as urine osmolality, 24-hour urine total volume and others. RESULTS: The final WIRWI is composed of 17 items assessing physical and mental dimensions. Items were selected based on their content and face validity. Exploratory and confirmatory factor analyses yielded Cronbach's alpha of 0.87 and 0.86, respectively. The final confirmatory factor analysis demonstrated that the model estimates were satisfactory for the constructs. Statistically significant correlations with the SF-36, total liquid consumption and simple water consumption were observed. CONCLUSION: The resulting WIRWI is a reliable tool for assessing wellbeing associated with consumption of plain water in Mexican adults and could be useful for similar groups. PMID- 27388903 TI - Integrating biomedical and herbal medicine in Ghana - experiences from the Kumasi South Hospital: a qualitative study. AB - BACKGROUND: Over the past decade there has been growing interest in the use of herbal medicine both in developed and developing countries. Given the high proportion of patients using herbal medicine in Ghana, some health facilities have initiated implementation of herbal medicine as a component of their healthcare delivery. However, the extent to which herbal medicine has been integrated in Ghanaian health facilities, how integration is implemented and perceived by different stakeholders has not been documented. The study sought to explore these critical issues at the Kumasi South Hospital (KSH) and outline the challenges and motivations of the integration process. METHODS: Qualitative phenomenological exploratory study design involving fieldwork observations, focus group discussion, in-depth interviews and key informants' interviews was employed to collect data. RESULTS: Policies and protocols outlining the definition, process and goals of integration were lacking, with respondents sharing different views about the purpose and value of integration of herbal medicine within public health facilities. Key informants were supportive of the initiative. Whilst biomedical health workers perceived the system to be parallel than integrated, health personnel providing herbal medicine perceived the system as integrated. Most patients were not aware of the herbal clinic in the hospital but those who had utilized services of the herbal clinic viewed the clinic as part of the hospital. CONCLUSIONS: The lack of a regulatory policy and protocol for the integration seemed to have led to the different perception of the integration. Policy and protocol to guide the integration are key recommendations. PMID- 27388901 TI - Characterization of Breast Cancer Preclinical Models Reveals a Specific Pattern of Macrophage Polarization. AB - Drug discovery efforts have focused on the tumor microenvironment in recent years. However, few studies have characterized the stroma component in patient derived xenografts (PDXs) and genetically engineered mouse models (GEMs). In this study, we characterized the stroma in various models of breast cancer tumors in mice. We performed transcriptomic and flow cytometry analyses on murine populations for a series of 25 PDXs and the two most commonly used GEMs (MMTV PyMT and MMTV-erBb2). We sorted macrophages from five models. We then profiled gene expression in these cells, which were also subjected to flow cytometry for phenotypic characterization. Hematopoietic cell composition, mostly macrophages and granulocytes, differed between tumors. Macrophages had a specific polarization phenotype related to their M1/M2 classification and associated with the expression of genes involved in the recruitment, invasion and metastasis processes. The heterogeneity of the stroma component of the models studied suggests that tumor cells modify their microenvironment to satisfy their needs. Our observations suggest that such models are of relevance for preclinical studies. PMID- 27388905 TI - Effects of non-severe acute kidney injury on clinical outcomes in critically ill patients. PMID- 27388904 TI - Kanamycin inhibits daidzein metabolism and abilities of the metabolites to prevent bone loss in ovariectomized mice. AB - BACKGROUND: Daidzein is an isoflavone derived from soybeans that exerts preventive effects on bone loss in ovariectomized (OVX) animals. These effects have been correlated with increasing serum equol levels. In the present study, we investigated the effects of antibiotic intake on equol metabolism from daidzein, and the corresponding levels of bone loss in OVX mice. METHODS: Eight-week-old female ddY mice (n = 42) were either ovariectomized (OVX) or subjected to a sham operation (sham). OVX mice were then divided into six dietary subgroups: control diet (control), 0.3 % kanamycin diet (KN), 0.1 % daidzein diet (Dz), 0.1 % daidzein and 0.0375 % kanamycin diet (Dz+KN3.75), 0.1 % daidzein and 0.075 % kanamycin diet (Dz+KN7.5), and 0.1 % daidzein and 0.3 % kanamycin diet (Dz+KN30). The mice were fed their respective diets for 4 weeks. RESULTS: Uterine weight and femoral bone mineral density (BMD) were significantly lower in the OVX mice compared in the sham mice. No significant differences in uterine weight were observed among all OVX dietary subgroups. The Dz subgroup was found to exhibit higher plasma equol and O-desmethylangolensin (O-DMA) concentrations, as well as greater femoral BMD, compared to all other OVX subgroups. Furthermore, when compared to the Dz group, kanamycin intake decreased plasma equol and O-DMA concentrations, as well as femoral BMD in the OVX mice. CONCLUSIONS: These results suggest that kanamycin intake inhibited the conversion of daidzein to equol and O-DMA, blocking the preventive effects of daidzein on bone loss in OVX mice. Therefore, the bone-protective effects of daidzein intake may be predominantly associated with increased plasma concentrations of either equol or O-DMA. PMID- 27388906 TI - Novel use of non-ablative fractional photothermolysis for cafe-au-lait macules in darker skin types. AB - IMPORTANCE: The removal of cafe-au-lait macules (CALMs) in patients with darker skin phototypes poses a significant challenge due to limited available therapeutic options and increased risk of adverse effects, including permanent scarring and further dyspigmentation. Herein, we demonstrate the novel use of non ablative fractional photothermolysis for the safe removal of CALMs in individuals with Fitzpatrick skin type (FST) IV-V. OBSERVATIONS: Retrospective analysis of four patients (FST IV-V) with CALMs revealed that three of these patients had greater than 50% clearance after multiple treatment sessions with the non ablative fractional 1,550-nm erbium-doped fiber laser. CONCLUSIONS AND RELEVANCE: This report demonstrates the utility and safety of non-ablative fractional resurfacing in the treatment of CALMs in darker skin phototypes. Lasers Surg. Med. 49:84-87, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27388908 TI - Correction: Correlation between Serum Levels of 3,3',5'-Triiodothyronine and Thyroid Hormones Measured by Liquid Chromatography-Tandem Mass Spectrometry and Immunoassay. AB - [This corrects the article DOI: 10.1371/journal.pone.0138864.]. PMID- 27388907 TI - Effects of Heavy Drinking on T-Cell Phenotypes Consistent with Immunosenescence in Untreated HIV Infection. AB - BACKGROUND: The role of alcohol consumption in HIV-related adaptive immune dysfunction is debated. We hypothesized that heavy drinking would be associated with greater evidence of immunosenescence (i.e., aging-related decline of adaptive immune function) among antiretroviral therapy (ART)-naive HIV-infected individuals. METHODS: Using data from the Russia ARCH cohort study, we conducted a cross-sectional analysis of ART-naive HIV-infected individuals recruited between 2012 and 2014. INDEPENDENT VARIABLE: Heavy drinking defined as >4 standard drinks in a day (or >14 standard drinks per week) for men and >3 per day (or >7 per week) for women, respectively. DEPENDENT VARIABLES: Percentage of CD8+ and CD4+ T-cells with a phenotype consistent with immunosenescence (i.e., expressing CD28- CD57+, or memory [CD45RO+ CD45RA+] phenotype and not the naive [CD45RO- CD45RA+] phenotype). STATISTICAL ANALYSIS: Multiple linear regression adjusted for confounders. RESULTS: Of 214 eligible participants, 61% were heavy drinkers. Mean age was 33 years and the cohort was predominantly male (72%). Hepatitis C prevalence was high (87%) and mean log10 HIV-1 RNA copies/ml was 4.6. We found no significant differences by drinking status in the percentage of immunosenescent, memory, or naive CD8+ or CD4+ T-cells. CONCLUSIONS: In this cross-sectional analysis, heavy drinking in the setting of untreated HIV infection did not appear to be associated with alterations in T-cell phenotypes consistent with immunosenescence. To substantiate these findings, longitudinal studies should assess whether changes in alcohol consumption are associated with changes in these and other immunosenescent T-cell phenotypes. PMID- 27388909 TI - Kangaroo supported diagonal flexion positioning: New insights into skin-to-skin contact for communication between mothers and very preterm infants. AB - OBJECTIVE: Skin-to-skin contact shows benefits in the relationship developed between a mother and her premature infant. In the skin-to-skin session, face-to face exchanges are impossible in vertical infant positioning. We therefore undertook an observational, prospective, single-center study using kangaroo "supported diagonal flexion" (SDF) positioning. The first aim was to evaluate the safety of kangaroo SDF positioning compared to the usual vertical positioning. The second aim was to evaluate SDF positioning on early communication between the mother and her infant and to improve their well-being. PARTICIPANTS AND SETTING: Fifteen mothers and their very premature infants (birth 26<32 weeks' gestation) were assigned to one of the two kangaroo positioning modes, either the current vertical positioning (n=7) or SDF positioning (n=8). DESIGN: Physiological variables and critical events were recorded before, during, and after ten successive skin-to-skin contact sessions. The first and last sessions were videotaped to allow later behavioral measurements. Mothers' risk for depression and feelings about the way they experienced communication with their infant were assessed through questionnaires. RESULTS: In terms of the infant's physiology, no negative effects were associated with SDF positioning in comparison with the usual vertical positioning. SDF positioning led to fewer disorganized gestures, negative vocalizations, and drowsiness, in favor of more deep sleep. SDF led to more mother-infant eye-to-eye contact as well as maternal vocalizations, smiles, and caressing, although these differences did not reach significance. The score for the risk of postnatal depression decreased significantly between the first and the last session in the SDF group, whereas it did not change in the vertical positioning group. CONCLUSION: These results support the idea that the kangaroo SDF positioning technique is physiologically safe, has obvious immediate benefits on mothers' infant-directed communicative behaviors, and respects the baby's naturally flexed and asymmetrical tonic neck posture. It is an innovative, inexpensive, easy-to-use technique in daily practice, by all healthcare professionals working in a neonatal intensive care unit. These data suggest that the current kangaroo positioning technique could be improved. More studies are needed to confirm the benefits and safety of the kangaroo SDF positioning in larger groups of preterm infants. PMID- 27388910 TI - Acceleration of Expectation-Maximization algorithm for length-biased right censored data. AB - Vardi's Expectation-Maximization (EM) algorithm is frequently used for computing the nonparametric maximum likelihood estimator of length-biased right-censored data, which does not admit a closed-form representation. The EM algorithm may converge slowly, particularly for heavily censored data. We studied two algorithms for accelerating the convergence of the EM algorithm, based on iterative convex minorant and Aitken's delta squared process. Numerical simulations demonstrate that the acceleration algorithms converge more rapidly than the EM algorithm in terms of number of iterations and actual timing. The acceleration method based on a modification of Aitken's delta squared performed the best under a variety of settings. PMID- 27388911 TI - Complementary and Alternative Medicine for Atopic Dermatitis: An Evidence-Based Review. AB - BACKGROUND: Complementary and alternative interventions are becoming increasingly utilized as adjuncts to conventional treatment of atopic dermatitis (AD). While the number of studies continues to grow, the vastness of the subject coupled with the relatively poor quality and small size of the studies limit their usefulness to clinicians. PURPOSE: Our aim was to comprehensively review randomized controlled trials (RCTs) of complementary and alternative therapies for AD. METHODS: Searches were performed on PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and the Global Resource for EczemA Trial (GREAT) databases, focusing on RCTs of alternative or complementary AD therapies, with a sample size of >=10, through March 2015 and limited to the English language. A total of 70 manuscripts met the inclusion criteria and were included in the final analysis. RESULTS: There is at least some level I evidence to support the use of acupuncture and acupressure, stress-reducing techniques such as hypnosis, massage, and biofeedback, balneotherapy, herbal preparations (with many important caveats), certain botanical oils, oral evening primrose oil, vitamin D supplementation, and topical vitamin B12. Many other therapies either have sufficient data to suggest that they are ineffective, or simply do not have enough evidence to formulate a verdict. CONCLUSIONS: Careful review of the literature reveals several promising therapies in this domain; such findings may help direct further research that is necessary to bolster clinical recommendations for alternative or complementary treatments of AD. PMID- 27388912 TI - Recurrent surgical site infection of the spine diagnosed by dual (18)F-NaF-bone PET/CT with early-phase scan. AB - We report a case of a 31-year-old man who showed recurrently elevated level of the serum inflammatory marker C-reactive protein (CRP) after spinal operation. He underwent (18)F-flurodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and dual (18)F-sodium-fluoride ((18)F NaF) PET/CT with an additional early-phase scan to find a hidden inflammation focus. Only mildly increased (18)F-FDG was found at the surgical site of T11 spine on (18)F-FDG PET/CT. In contrast, dual (18)F-NaF bone PET/CT with early phase scan demonstrated focal active inflammation at the surgical site of T11 spine. After a revision operation of the T11 spine, serum CRP level decreased to the normal range without any symptom or sign of inflammation. Inflammatory focus in the surgical site of the spine can be detected with using dual (18)F-NaF bone PET/CT scan with early-phase scan. PMID- 27388913 TI - Intraoperative fine needle aspirations - diagnosis and typing of lung cancer in small biopsies: challenges and limitations. AB - BACKGROUND: Due to therapeutic implications with regard to both efficiency and safety of chemotherapy agents it is important to differentiate between subtypes of NSCLC. Up to today we experience a continuous reservation regarding the use of fine needle aspiration cytology. The aim of the present study is to estimate the value of cytologic criteria for lung cancer typing on small biopsies independent from all possible technique failures. METHODS: Between January 1997 and December 2008 760 intraoperative FNAC- (fine needle aspiration cytology) specimens from 702 patients have been examined. Cytologic evaluation and immediate communication of results to the surgeons followed. Afterwards, intraoperative cytologic findings were compared with final histologic diagnoses of the resected specimens. RESULTS: Intraoperative cytologic analysis yielded a sensitivity of 94.8 %, a specificity of 98.8 %. An overall positive predictive value of 99.8 % with respect to final histologic analysis of primary lung cancer was achieved. The highest value could be reached for adenocarcinomas, followed by carcinoids and squamous cell carcinomas. CONCLUSIONS: Lung cancer typing according to cytologic criteria is feasible and accurate as well as comparable with results of histologic analysis on small specimens. Herewith, clinicians can come up to the increasing demands on minimally invasive harvested specimens with regard to therapeutic implications. PMID- 27388914 TI - [Recommendations of the ESC guidelines regarding cardiovascular imaging]. AB - Cardiac imaging plays a key role in the diagnosis and risk stratification in the ESC guidelines for the management of patients with stable coronary artery disease. Demonstration of myocardial ischaemia guides the decision which further diagnostic and therapeutic strategy should be followed in these patients. One should, however, not forget that there are no randomised studies supporting this type of management. In patients with a low pretest probability coronary CT angiography is the optimal tool to exclude coronary artery stenoses rapidly and effectively. In the near future, however, better data is needed showing how much cardiac imaging is really necessary and how cost-effective it is in patients with stable coronary artery disease. PMID- 27388915 TI - Enhanced detection with spectral imaging fluorescence microscopy reveals tissue- and cell-type-specific compartmentalization of surface-modified polystyrene nanoparticles. AB - BACKGROUND: Precisely targeted nanoparticle delivery is critically important for therapeutic applications. However, our knowledge on how the distinct physical and chemical properties of nanoparticles determine tissue penetration through physiological barriers, accumulation in specific cells and tissues, and clearance from selected organs has remained rather limited. In the recent study, spectral imaging fluorescence microscopy was exploited for precise and rapid monitoring of tissue- and cell-type-specific distribution of fluorescent polystyrene nanoparticles with chemically distinct surface compositions. METHODS: Fluorescent polystyrene nanoparticles with 50-90 nm diameter and with carboxylated- or polyethylene glycol-modified (PEGylated) surfaces were delivered into adult male and pregnant female mice with a single intravenous injection. The precise anatomical distribution of the particles was investigated by confocal microscopy after a short-term (5 min) or long-term (4 days) distribution period. In order to distinguish particle-fluorescence from tissue autofluorescence and to enhance the detection-efficiency, fluorescence spectral detection was applied during image acquisition and a post hoc full spectrum analysis was performed on the final images. RESULTS: Spectral imaging fluorescence microscopy allowed distinguishing particle-fluorescence from tissue-fluorescence in all examined organs (brain, kidney, liver, spleen and placenta) in NP-treated slice preparations. In short time distribution following in vivo NP-administration, all organs contained carboxylated-nanoparticles, while PEGylated-nanoparticles were not detected in the brain and the placenta. Importantly, nanoparticles were not found in any embryonic tissues or in the barrier-protected brain parenchyma. Four days after the administration, particles were completely cleared from both the brain and the placenta, while PEGylated-, but not carboxylated-nanoparticles, were stuck in the kidney glomerular interstitium. In the spleen, macrophages accumulated large amount of carboxylated and PEGylated nanoparticles, with detectable redistribution from the marginal zone to the white pulp during the 4-day survival period. CONCLUSIONS: Spectral imaging fluorescence microscopy allowed detecting the tissue- and cell-type-specific accumulation and barrier-penetration of polystyrene nanoparticles with equal size but chemically distinct surfaces. The data revealed that polystyrene nanoparticles are retained by the reticuloendothelial system regardless of surface functionalization. Taken together with the increasing production and use of nanoparticles, the results highlight the necessity of long-term distribution studies to estimate the potential health-risks implanted by tissue-specific nanoparticle accumulation and clearance. PMID- 27388916 TI - Effect of high hydrostatic pressure treatment on isoquercetin production from rutin by commercial alpha-L-rhamnosidase. AB - OBJECTIVES: To optimize conversion of rutin to isoquercetin by commercial alpha-L rhamnosidase using high hydrostatic pressure (HHP). RESULTS: The de rhamnosylation activity of alpha-L-rhamnosidase for isoquercetin production was maximal at pH 6.0 and 50 degrees C using HHP (150 MPa). The enzyme showed high specificity for rutin. The specific activity for rutin at HHP was 1.5-fold higher than that at atmospheric pressure. The enzyme completely hydrolysed 20 mM rutin in tartary buckwheat extract after 2 h at HHP, with a productivity of 10 mM h( 1). The productivity and conversion were 2.2- and 1.5-fold higher at HHP than at atmospheric pressure, respectively. CONCLUSIONS: This is the first report concerning the enzymatic hydrolysis of isoquercetin in tartary buckwheat at HHP. PMID- 27388917 TI - Spontaneous Metacognition in Rhesus Monkeys. AB - Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. PMID- 27388919 TI - A Carbonylation Approach Toward Activation of Csp2-H and Csp3-H Bonds: Cu Catalyzed Regioselective Cross Coupling of Imidazo[1,2-a]pyridines with Methyl Hetarenes. AB - An efficient copper-catalyzed selective cross coupling of imidazo[1,2-a]pyridines with methyl hetarenes has been reported. This transformation opened a new route to synthesize the C-3 carbonyl imidazo[1,2-a]pyridine derivative, which is a common structural motif in natural products and pharmaceuticals. (18)O-labeling experiments indicated that the oxygen source of products originated from O2. PMID- 27388918 TI - Interleukin-22 is elevated in lavage from patients with lung cancer and other pulmonary diseases. AB - BACKGROUND: Interleukin-22 (IL-22) is involved in lung diseases such as pneumonia, asthma and lung cancer. Lavage mirrors the local environment, and may provide insights into the presence and role of IL-22 in patients. METHODS: Bronchoscopic lavage (BL) samples (n = 195, including bronchoalveolar lavage and bronchial washings) were analysed for IL-22 using an enzyme-linked immunosorbent assay. Clinical characteristics and parameters from lavage and serum were correlated with lavage IL-22 concentrations. RESULTS: IL-22 was higher in lavage from patients with lung disease than in controls (38.0 vs 15.3 pg/ml, p < 0.001). Patients with pneumonia and lung cancer had the highest concentrations (48.9 and 33.0 pg/ml, p = 0.009 and p < 0.001, respectively). IL-22 concentration did not correlate with systemic inflammation. IL-22 concentrations did not relate to any of the analysed cell types in BL indicating a potential mixed contribution of different cell populations to IL-22 production. CONCLUSIONS: Lavage IL-22 concentrations are high in patients with lung cancer but do not correlate with systemic inflammation, thus suggesting that lavage IL-22 may be related to the underlying malignancy. Our results suggest that lavage may represent a distinct compartment where the role of IL-22 in thoracic malignancies can be studied. PMID- 27388920 TI - Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry. AB - 1. In this study, the stereoselective pharmacokinetics of rhynchophylline (RIN) and isorhynchophylline (IRN) in rat plasma were investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2. A rapid, robust and sensitive LC-MS/MS method for simultaneous quantification of RIN and IRN in rat plasma was established and validated. Chromatographic separation was performed on a Poroshell 120 EC-C18 column under a gradient elution with methanol and water containing 0.01% ammonia as mobile phase. Calibration curve was linear over a concentration range of 1-2000 ng/mL for both epimers. 3. After intravenous administration, there was no apparent difference in pharmacokinetic parameters between two epimers. However, after oral administration, RIN showed remarkable higher plasma exposure than IRN. The bioavailability, Cmax and AUC0-t of RIN were about 9.2-fold, 6.4-fold and 9.1-fold higher than those of IRN at 10 mg/kg, and 7.8-fold, 4.3-fold and 7.7-fold at 20 mg/kg, respectively. Additionally, with dosage enhanced from 10 mg/kg to 20 mg/kg, the plasma concentrations of RIN or IRN increased significantly and the bioavailability enhanced about three times. 4. In conclusion, the results of this work demonstrated for the first time that the pharmacokinetics of RIN and IRN have stereoselectivity. PMID- 27388921 TI - Aqueous-Based Fabrication of Low-VOC Nanostructured Block Copolymer Films as Potential Marine Antifouling Coatings. AB - The ability to fabricate nanostructured films by exploiting the phenomenon of microphase separation has made block copolymers an invaluable tool for a wide array of coating applications. Standard approaches to engineering nanodomains commonly involve the application of organic solvents, either through dissolution or annealing protocols, resulting in the release of volatile organic compounds (VOCs). In this paper, an aqueous-based method of fabricating low-VOC nanostructured block copolymer films is presented. The reported procedure allows for the phase transfer of water insoluble triblock copolymer, poly(styrene-block 2 vinylpyridine-block-ethylene oxide) (PS-b-P2VP-b-PEO), from a water immiscible phase to an aqueous environment with the assistance of a diblock copolymeric phase transfer agent, poly(styrene-block-ethylene oxide) (PS-b-PEO). Phase transfer into the aqueous phase results in self-assembly of PS-b-P2VP-b-PEO into core-shell-corona micelles, which are characterized by dynamic light scattering techniques. The films that result from coating the micellar solution onto Si/SiO2 surfaces exhibit nanoscale features that disrupt the ability of a model foulant, a zoospore of Ulva linza, to settle. The multilayered architecture consists of a pH-responsive P2VP-"shell" which can be stimulated to control the size of these features. The ability of these nanostructured thin films to resist protein adsorption and serve as potential marine antifouling coatings is supported through atomic force microscopy (AFM) and analysis of the settlement of Ulva linza zoospore. Field trials of the surfaces in a natural environment show the inhibition of macrofoulants for 1 month. PMID- 27388922 TI - Reply to: "miR-122 expression is not regulated during activation of hepatic stellate cells". PMID- 27388923 TI - Validation of the Baveno VI criteria to identify low risk cirrhotic patients not requiring endoscopic surveillance for varices. AB - BACKGROUND & AIMS: The Baveno VI guidelines propose that cirrhotic patients with a liver stiffness measurement (LSM) <20kPa and a platelet count >150,000/MUl can avoid screening endoscopy as their combination is highly specific for excluding clinically significant varices. The aim of the study was to validate these criteria. METHODS: Transient elastography data was collected from two institutions from 2006-2015. Inclusion criteria were a LSM ?10kPa and an upper gastrointestinal endoscopy within 12months, with a diagnosis of compensated chronic liver disease. Exclusion criteria were porto-mesenteric-splenic vein thrombosis and non-cirrhotic portal hypertension. Varices were graded as low risk (grade <2) or high risk (grade ?2). RESULTS: The study included 310 patients (169 (55%) hepatitis C, and 275 (89%) Child-Pugh A). Varices were present in 23% cases, with 5% prevalence of high risk varices. Overall 102/310 (33%) met the Baveno VI criteria. Within this group 11% had varices and 2% had high risk varices, representing 2/15 (13%) of all high risk varices. The Baveno VI criteria gave a sensitivity 0.87, specificity 0.34, positive predictive value 0.06, negative predictive value 0.98, positive likelihood ratio 1.31 and negative likelihood ratio 0.39. The AUROC for LSM and platelet count combined was 0.746. CONCLUSIONS: The Baveno VI criteria performed well correctly identifying 98% of patients who could safely avoid endoscopy. LAY SUMMARY: This study examines the effectives of a recent set of guidelines published by the Baveno VI conference, which states that patients with chronic liver disease and a low liver stiffness (<20kPa) and high platelet count (>150) are at low risk of having varices and do not need a screening endoscopy. Varices are a complication of cirrhosis, confer a risk of serious bleeding, and can be diagnosed and treated by endoscopy. Our study reviewed the clinical records of patients who have had liver stiffness scans and endoscopy over a 9-year period at two hospitals. The results show that only about 2% of patients who meet the Baveno VI criteria will be miss-classified as not having varices. PMID- 27388924 TI - miR-122 expression is not regulated during activation of hepatic stellate cells. PMID- 27388926 TI - Combining the Many-Body GW Formalism with Classical Polarizable Models: Insights on the Electronic Structure of Molecular Solids. AB - We present an original hybrid QM/MM scheme merging the many-body Green's function GW formalism with classical discrete polarizable models and its application to the paradigmatic case of a pentacene crystal. Our calculated transport gap is found to be in excellent agreement with reference periodic bulk GW calculations, together with properly parametrized classical microelectrostatic calculations, and with photoionization measurements at crystal surfaces. More importantly, we prove that the gap is insensitive to the partitioning of pentacene molecules in QM and MM subsystems, as a result of the mutual compensation of quantum and classical polarizabilities, clarifying the relation between polarization energy and delocalization. The proposed hybrid method offers a computationally attractive strategy to compute the full spectrum of charged excitations in complex molecular environments, accounting for both QM and MM contributions to the polarization energy, a crucial requirement in the limit of large QM subsystems. PMID- 27388925 TI - Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis. AB - BACKGROUND & AIMS: Direct-acting antivirals have become widely used for patients with chronic hepatitis C virus infection with decompensated cirrhosis. Virological responses are excellent and early improvements in liver function, at least in a proportion of patients, have been observed but the longer term impact of viral clearance on end-stage liver disease complications is unclear. METHODS: Prospective study of patients with decompensated cirrhosis who received 12weeks of all-oral direct-acting antivirals through the English Expanded Access Programme. Endpoints were deaths, liver transplantation, hepatocellular carcinoma, serious decompensation events, sepsis or hospitalisations, and MELD scores between start of therapy to 15months post-treatment start. An untreated cohort of patients was retrospectively studied over 6months for comparison. RESULTS: Amongst 317/406 patients who achieved sustained virological response at 24weeks post-treatment, there were 9 deaths (3%), 17 new liver cancers (5%), 39 transplantations (12%) and 52 with serious decompensations (16%), over 15months. When compared to the first six months from treatment start and to untreated patients, there was a reduction in incidence of decompensations [30/406 (7%) in months 6-15 and 72/406 (18%) in months 0-6 for treated patients vs. 73/261 (28%) in untreated patients]. There was no significant difference in liver cancer incidence (10/406 (2.5%) in months 6-15 and 17/406 (4%) in months 0-6 for treated patients vs. 11/261 (4%) in untreated patients). CONCLUSIONS: This study suggests that antiviral therapy in patients with decompensated cirrhosis led to prolonged improvement in liver function, with no evidence of paradoxical adverse impact nor increase in liver malignancy. LAY SUMMARY: This is a report of a large group of patients in England who have hepatitis C virus (HCV) infection with advanced liver disease. They have been treated with new anti-HCV drugs, which cured the infection in the majority. This study looks at their outcomes a year following treatment, in terms of deaths, cancers and other complications of advanced liver disease. We conclude that in most patients anti-HCV treatment is beneficial even in advanced liver disease. PMID- 27388927 TI - The Effect of Donor Group Rigidification on the Electronic and Optical Properties of Arylamine-Based Metal-Free Dyes for Dye-Sensitized Solar Cells: A Computational Study. AB - One of the most significant aspects in the development of dye-sensitized solar cells is the exploration and design of high-efficiency and low-cost dyes. This paper reports the theoretical design of various triphenylamine analogues, wherein the central nitrogen moiety establishes an sp(2)-hybridization, which endows a significant participation in the charge-transfer properties. Density functional theory (DFT) and time-dependent DFT methodologies were utilized to investigate the geometry, electronic structure, photochemical properties, and electrochemical properties of these dyes. Different exchange-correlation functionals were initially evaluated to establish a proper methodology for calculating the excited state energy of the reference dye, known as DIA3. Consequently, TD-LC-omegaPBE with a damping parameter of 0.175 Bohr(-1) best correlates with the experimental value. Four new dyes, namely, Dhk1, Dhk2, Dhk3, and Dhk4, were designed by modifying the rigidity of the donor moiety. According to the results, altering the type and position of binding in the donor group leads to distinct planarity of the dyes, which significantly affects their properties. The designed Dhk4 dye showed more red-shifted and broadened absorption spectra owing to the enhanced coplanarity between its donor and pi-bridge moiety, which brings an advantage for its potential use as sensitizer for photovoltaic applications. PMID- 27388928 TI - Measuring the Value of New Medications and Implications for Medicare's Proposed Part B Drug Payment Model. PMID- 27388930 TI - CDC's Response to the 2014-2016 Ebola Epidemic - Guinea, Liberia, and Sierra Leone. AB - CDC's response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa was the largest in the agency's history and occurred in a geographic area where CDC had little operational presence. Approximately 1,450 CDC responders were deployed to Guinea, Liberia, and Sierra Leone since the start of the response in July 2014 to the end of the response at the end of March 2016, including 455 persons with repeat deployments. The responses undertaken in each country shared some similarities but also required unique strategies specific to individual country needs. The size and duration of the response challenged CDC in several ways, particularly with regard to staffing. The lessons learned from this epidemic will strengthen CDC's ability to respond to future public health emergencies. These lessons include the importance of ongoing partnerships with ministries of health in resource-limited countries and regions, a cadre of trained CDC staff who are ready to be deployed, and development of ongoing working relationships with U.S. government agencies and other multilateral and nongovernment organizations that deploy for international public health emergencies. CDC's establishment of a Global Rapid Response Team in June 2015 is anticipated to meet some of these challenges. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west africa/partners.html). PMID- 27388929 TI - IgE-associated food allergy alters the presentation of paediatric eosinophilic esophagitis. AB - BACKGROUND: Links between food allergens and eosinophilic esophagitis (EoE) have been established, but the interplay between EoE- and IgE-associated immediate hypersensitivity to foods remains unclear. OBJECTIVE: We sought to determine the prevalence of IgE-associated food allergy at the time of diagnosis of EoE in children and to determine whether differences existed in presentation and disease compared to subjects with EoE alone. METHODS: Eosinophilic esophagitis patients were stratified based on the diagnosis of IgE-associated immediate hypersensitivity (EoE + IH vs. EoE-IH). Clinical, histologic, pathologic, and endoscopic differences were investigated using a retrospective database. RESULTS: We found that 29% of the 198 EoE patients in our cohort had EoE + IH. These subjects presented at a younger age than those without IH (6.05 vs. 8.09 years, P = 0.013) and were more likely to have comorbid allergic disease. Surprisingly, the EoE + IH group presented with significantly different clinical symptoms, with increased dysphagia, gagging, cough, and poor appetite compared to their counterparts in the EoE-IH group. Male gender, allergic rhinitis, the presence of dysphagia, and younger age were independently associated with having EoE + IH. Specific IgE levels to common EoE-associated foods were higher in EoE + IH, regardless of eliciting immediate hypersensitivity symptoms. In contrast, IgE levels for specific foods triggering EoE were relatively lower in both the groups than IgE levels for immediate reactions. CONCLUSIONS AND CLINICAL RELEVANCE: Immediate hypersensitivity is common in children with EoE and identifies a population of EoE patients with distinct clinical characteristics. Our study describes a subtype of EoE in which IgE-mediated food allergy may impact the presentation of paediatric EoE. PMID- 27388931 TI - Impact of Conversion to Open Surgery on Early Postoperative Morbidity After Laparoscopic Resection for Rectal Adenocarcinoma: A Retrospective Study. AB - BACKGROUND: The impact of conversion to open surgery after a laparoscopic resection for rectal adenocarcinoma on postoperative morbidity is still unclear. Most previous studies included colon and rectal carcinomas and produced conflicting results. The aim of this study was to investigate the impact of conversion to open surgery on early postoperative morbidity in patients who underwent a laparoscopic resection for rectal adenocarcinoma. METHODS: This was a retrospective bicentric study. It included all consecutive patients who underwent a laparoscopic resection for nonmetastatic rectal adenocarcinoma between January 2005 and December 2013. The impact of conversion to open surgery on 30-day postoperative morbidity was analyzed by univariate and multivariate analyses. Risk factors for conversion were also investigated by univariate and multivariate analyses. RESULTS: One hundred thirty-one patients were included. The conversion rate was 26.7%. The global 30-day morbidity rate was 31.3% (41 patients). The conversion to open surgery was associated with higher rates of postoperative complications, anastomotic leaks, and reoperations. It was also an independent predictive factor to postoperative morbidity in the multivariate analysis (P = .01; odds ratio 2.86; 95% confidence interval [CI] 1.23-6.63), in addition to T4 tumors (P = .04; odds ratio 3.92; 95% CI 1.05-14.61). Risk factors for conversion in the multivariate analysis were T4 tumors (P = .006; odds ratio 6.09; 95% CI 1.66-22.32) and the height of the tumor (P = .025; odds ratio 2.7; 95% CI 1.13 6.43). CONCLUSIONS: This study showed that conversion to open surgery after laparoscopic proctectomy for rectal adenocarcinoma was associated with higher rates of early postoperative complications. It also showed that T4 tumors and the height of the tumor were independent factors associated with the conversion to open surgery. Reducing postoperative morbidity could be achieved by a better patient selection and a policy of early conversion. PMID- 27388932 TI - Metal Oxide Assisted Preparation of Core-Shell Beads with Dense Metal-Organic Framework Coatings for the Enhanced Extraction of Organic Pollutants. AB - Dense and homogeneous metal-organic framework (MOF) coatings on functional bead surfaces are easily prepared by using intermediate sacrificial metal oxide coatings containing the metal precursor of the MOF. Polystyrene (PS) beads are coated with a ZnO layer to give ZnO@PS core-shell beads. The ZnO@PS beads are reactive in the presence of 2-methylimidazole to transform part of the ZnO coating into a porous zeolitic imidazolate framework-8 (ZIF-8) external shell positioned above the internal ZnO precursor shell. The obtained ZIF-8@ZnO@PS beads can be easily packed in column format for flow-through applications, such as the solid-phase extraction of trace priority-listed environmental pollutants. The prepared material shows an excellent permeance to flow when packed as a column to give high enrichment factors, facile regeneration, and excellent reusability for the extraction of the pollutant bisphenol A. It also shows an outstanding performance for the simultaneous enrichment of mixtures of endocrine disrupting chemicals (bisphenol A, 4-tert-octylphenol and 4-n-nonylphenol), facilitating their analysis when present at very low levels (<1 MUg L(-1) ) in drinking waters. For the extraction of the pollutant bisphenol A, the prepared ZIF-8@ZnO@PS beads also show a superior extraction and preconcentration capacity to that of the PS beads used as precursors and the composite materials obtained by the direct growth of ZIF-8 on the surface of the PS beads in the absence of metal oxide intermediate coatings. PMID- 27388933 TI - Clinical efficacy of istradefylline on lower urinary tract symptoms in Parkinson's disease. PMID- 27388934 TI - Pathogenic mechanisms underlying X-linked Charcot-Marie-Tooth neuropathy (CMTX6) in patients with a pyruvate dehydrogenase kinase 3 mutation. AB - Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. An X-linked form of CMT (CMTX6) is caused by a missense mutation (R158H) in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. PDK3 is one of 4 isoenzymes that negatively regulate the activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation of its first catalytic component pyruvate dehydrogenase (designated as E1). Mitochondrial PDC catalyses the oxidative decarboxylation of pyruvate to acetyl CoA and links glycolysis to the energy-producing Krebs cycle. We have previously shown the R158H mutation confers PDK3 enzyme hyperactivity. In this study we demonstrate that the increased PDK3 activity in patient fibroblasts (PDK3(R158H)) leads to the attenuation of PDC through hyper-phosphorylation of E1 at selected serine residues. This hyper-phosphorylation can be reversed by treating the PDK3(R158H) fibroblasts with the PDK inhibitor dichloroacetate (DCA). In the patient cells, down-regulation of PDC leads to increased lactate, decreased ATP and alteration of the mitochondrial network. Our findings highlight the potential to develop specific drug targeting of the mutant PDK3 as a therapeutic approach to treating CMTX6. PMID- 27388935 TI - Zinc contributes to acute cerebral ischemia-induced blood-brain barrier disruption. AB - Zinc ions are stored in synaptic vesicles and cerebral ischemia triggers their release from the terminals of neurons. Zinc accumulation in neurons has been shown to play an important role in neuronal death following ischemia. However, almost nothing is known about whether zinc is involved in ischemia-induced blood brain barrier (BBB) disruption. Herein, we investigated the contribution of zinc to ischemia-induced acute BBB disruption and the possible molecular mechanisms using both cellular and animal models of cerebral ischemia. Zinc greatly increased BBB permeability and exacerbated the loss of tight junction proteins (Occludin and Claudin-5) in the endothelial monolayer under oxygen glucose deprivation conditions. In cerebral ischemic rats, a dramatically elevated level of zinc accumulation in microvessels themselves was observed in isolated microvessels and in situ, showing the direct interaction of zinc on ischemic microvessels. Treatment with a specific zinc chelator N,N,N',N'-tetrakis(2 pyridylmethyl) ethylenediamine (TPEN), even at 60-min post-ischemia onset, could greatly attenuate BBB permeability in the ischemic rats as measured by Evan's Blue extravasation, edema volume and magnetic resonance imaging. Furthermore, zinc accumulation in microvessels activated the superoxide/matrix metalloproteinase-9/-2 pathway, which leads to the loss of tight junction proteins (Occludin and Claudin-5) and death of endothelial cells in microvessels themselves. Our findings reveal a novel mechanism of cerebral ischemia-induced BBB damage, and implicate zinc as an effective and viable new target for reducing acute BBB damage following ischemic stroke. PMID- 27388936 TI - Disruption of snRNP biogenesis factors Tgs1 and pICln induces phenotypes that mirror aspects of SMN-Gemins complex perturbation in Drosophila, providing new insights into spinal muscular atrophy. AB - The neuromuscular disorder, spinal muscular atrophy (SMA), results from insufficient levels of the survival motor neuron (SMN) protein. Together with Gemins 2-8 and Unrip, SMN forms the large macromolecular SMN-Gemins complex, which is known to be indispensable for chaperoning the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). It remains unclear whether disruption of this function is responsible for the selective neuromuscular degeneration in SMA. In the present study, we first show that loss of wmd, the Drosophila Unrip orthologue, has a negative impact on the motor system. However, due to lack of a functional relationship between wmd/Unrip and Gemin3, it is likely that Unrip joined the SMN-Gemins complex only recently in evolution. Second, we uncover that disruption of either Tgs1 or pICln, two cardinal players in snRNP biogenesis, results in viability and motor phenotypes that closely resemble those previously uncovered on loss of the constituent members of the SMN-Gemins complex. Interestingly, overexpression of both factors leads to motor dysfunction in Drosophila, a situation analogous to that of Gemin2. Toxicity is conserved in the yeast S. pombe where pICln overexpression induces a surplus of Sm proteins in the cytoplasm, indicating that a block in snRNP biogenesis is partly responsible for this phenotype. Importantly, we show a strong functional relationship and a physical interaction between Gemin3 and either Tgs1 or pICln. We propose that snRNP biogenesis is the pathway connecting the SMN-Gemins complex to a functional neuromuscular system, and its disturbance most likely leads to the motor dysfunction that is typical in SMA. PMID- 27388937 TI - The number of striatal cholinergic interneurons expressing calretinin is increased in parkinsonian monkeys. AB - The most abundant interneurons in the primate striatum are those expressing the calcium-binding protein calretinin (CR). The present immunohistochemical study provides detailed assessments of their morphological traits, number, and topographical distribution in normal monkeys (Macaca fascicularis) and in monkeys rendered parkinsonian (PD) by MPTP intoxication. In primates, the CR+ striatal interneurons comprise small (8-12MUm), medium (12-20MUm) and large-sized (20 45MUm) neurons, each with distinctive morphologies. The small CR+ neurons were 2 3 times more abundant than the medium-sized CR+ neurons, which were 20-40 times more numerous than the large CR+ neurons. In normal and PD monkeys, the density of small and medium-sized CR+ neurons was twice as high in the caudate nucleus than in the putamen, whereas the inverse occurred for the large CR+ neurons. Double immunostaining experiments revealed that only the large-sized CR+ neurons expressed choline acetyltransferase (ChAT). The number of large CR+ neurons was found to increase markedly (4-12 times) along the entire anteroposterior extent of both the caudate nucleus and putamen of PD monkeys compared to controls. Comparison of the number of large CR-/ChAT+ and CR+/ChAT+ neurons together with experiments involving the use of bromo-deoxyuridine (BrdU) as a marker of newly generated cells showed that it is the expression of CR by the large ChAT+ striatal interneurons, and not their absolute number, that is increased in the dopamine-depleted striatum. These findings reveal the modulatory role of dopamine in the phenotypic expression of the large cholinergic striatal neurons, which are known to play a crucial role in PD pathophysiology. PMID- 27388939 TI - Supplementation with Major Royal-Jelly Proteins Increases Lifespan, Feeding, and Fecundity in Drosophila. AB - The major royal-jelly proteins (MRJPs) are the main constituents responsible for the specific physiological role of royal jelly (RJ) in honeybees. Male and female Drosophila flies were fed diets containing either no MRJPs (A) or casein (B) at 1.25% (w/w) of diet or MRJPs at 1.25% (C), 2.50% (D), or 5.00% (E). Diets B, C, D, and E increased mean lifespan by 4.3%, 9.0%, 12.4%, and 13.9% in males and by 5.8%, 9.7%, 20.0%, and 11.8% in females in comparison to results from diet A, respectively. The diet supplemented with 2.50% MRJPs seems to have the optimal dose to improve both physiological and biochemical measures related to aging in both sexes. Interestingly, lifespan extension by MRJPs in Drosophila was positively associated with feeding and fecundity and up-regulation of copper and zinc-superoxide dismutase (CuZn-SOD) and the Egfr-mediated signaling pathway. This study provides strong evidence that MRJPs are important components of RJ for prolonging lifespan in Drosophila. PMID- 27388938 TI - Sequencing-based diagnostics for pediatric genetic diseases: progress and potential. AB - INTRODUCTION: The last two decades have witnessed revolutionary changes in clinical diagnostics, fueled by the Human Genome Project and advances in high throughput, Next Generation Sequencing (NGS). We review the current state of sequencing-based pediatric diagnostics, associated challenges, and future prospects. AREAS COVERED: We present an overview of genetic disease in children, review the technical aspects of Next Generation Sequencing and the strategies to make molecular diagnoses for children with genetic disease. We discuss the challenges of genomic sequencing including incomplete current knowledge of variants, lack of data about certain genomic regions, mosaicism, and the presence of regions with high homology. Expert commentary: NGS has been a transformative technology and the gap between the research and clinical communities has never been so narrow. Therapeutic interventions are emerging based on genomic findings and the applications of NGS are progressing to prenatal genetics, epigenomics and transcriptomics. PMID- 27388940 TI - The epidemiology, prevalence and hospital outcomes of infants with gastroschisis. AB - OBJECTIVE: The purpose of this study is to evaluate recent trends in prevalence of gastroschisis among infants admitted for neonatal intensive care in the United States. STUDY DESIGN: Retrospective review of a de-identified patient data. The current study extends our observations through the end of 2007 to 2015. RESULTS: During the study period (1 January 1997 to 12 December 2015), there were 1 158 755 total discharges; 6023 (5.2/1000) had gastroschisis and 1885 (1.6/1000) had an omphalocele. Between 1997 and 2008, the reported rate of gastroschisis increased from 2.9 to 6.4/1000 discharges. From 2008 to 2011, the values have slowly decreased from 6.4 to 4.7/1000 discharges and since 2011 have been stable. The largest drop in the prevalence was in mothers who were <20 years old. In contrast, the reported rate of omphalocele was stable at 1 to 2/1000 discharges. CONCLUSION: The prevalence of gastroschisis increased from 1997 to 2008, and then declined thereafter. PMID- 27388943 TI - Tasmanian macular hole study: whole population-based incidence of full thickness macular hole. AB - PURPOSE: To determine the incidence of full thickness macular hole in the Tasmanian population. DESIGN: A whole population retrospective case series in Tasmania, Australia. METHODS: Patients diagnosed with full thickness macular hole (confirmed by optical coherence tomography (OCT) imaging) of both idiopathic and secondary causes were identified from April 2005 to April 2011 by a sole vitreoretinal surgeon servicing Tasmania. Baseline characteristics were recorded. The six-year incidence rate was calculated, based on the 2006 and 2011 Tasmanian census data. Incidence rates were age and sex standardized. PARTICIPANTS: One hundred forty-seven eyes of 136 patients. MAIN OUTCOME MEASURES: To determine the incidence (age and sex standardized) of full thickness macular holes in Tasmania, Australia. RESULTS: Idiopathic macular holes comprised 128 (87.1%). There were 116 cases of idiopathic Full Thickness Macular Hole in one or both eyes between 1 April 2005 and 31 April 2011. The six-year incidence of idiopathic full-thickness macular holes was 24.3 per 100 000 people, 4.05 per 100 000 per year, with the highest six-year incidence observed among women aged 70-79 years. CONCLUSION: This is the first global study to report OCT confirmed incidence rates of full thickness macular holes in a relatively static Australian population sub-group. PMID- 27388941 TI - Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps. AB - OBJECTIVE: Neonates with necrotizing enterocolitis (NEC) have higher calprotectin levels in stool than do healthy neonates. However, it is not known whether high stool calprotectin at the onset of bowel symptoms identifies neonates who truly have NEC vs other bowel disorders. STUDY DESIGN: Neonates were eligible for this study when an x-ray was ordered to 'rule-out NEC'. Stool calprotectin was quantified at that time and in a follow-up stool. Each episode was later categorized as NEC or not NEC. The location of calprotectin in the bowel was determined by immunohistochemistry. RESULTS: Neonates with NEC had higher initial and follow-up stool calprotectin levels than did neonates without NEC. Calprotectin in bowel from neonates with NEC was within neutrophil extracellular traps (NETs). CONCLUSION: At the onset of signs concerning for NEC, fecal calprotectin is likely to be higher in neonates with NEC. Calprotectin in their stools is exported from neutrophils via NETs. PMID- 27388942 TI - Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse. AB - OBJECTIVE: The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse. STUDY DESIGN: The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection. RESULTS: Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (P<0.001) and an additional 7.5% with low-level exposures. We identified an increased likelihood of exposure to drugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures. CONCLUSION: Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources. PMID- 27388944 TI - A multifunctional DNA origami as carrier of metal complexes to achieve enhanced tumoral delivery and nullified systemic toxicity. AB - The use of metal complexes in cancer treatment is hampered by the insufficient accumulation in tumor regions and observable systemic toxicity due to their nonspecificity in vivo. Herein we present a cancer-targeted DNA origami as biocompatible nanocarrier of metal complexes to achieve advanced antitumor effect. The formation of unique tetrahedral nanostructure of DNA cages effectively enhances the interaction between ruthenium polypyridyl complexes (RuPOP) and the cages, thus increasing the drug loading efficacy. Conjugation of biotin to the DNA-based nanosystem (Bio-cage@Ru) enhances its specific cellular uptake, drug retention and cytotoxicity against HepG2 cells. Different from free RuPOP and the cage itself, Bio-cage@Ru translocates to cell nucleus after internalization, where it undergoes self-immolative cleavage in response to DNases, leading to triggered drug release and induction of ROS-mediated cell apoptosis. Moreover, in the nude mice model, the nanosystem specifically accumulates in tumor sites, thus exhibits satisfactory in vivo antitumor efficacy, and alleviates the damage of liver, kidney, lung and heart function of nude mice induced by RuPOP and tumor xenografts. Collectively, this study demonstrates a strategy for construction of biocompatible and cancer-targeted DNA origami with enhanced anticancer efficacy and reduced toxicity for next generation cancer therapy. PMID- 27388945 TI - Balancing stealth and echogenic properties in an ultrasound contrast agent with drug delivery potential. AB - Contrast agents are currently being modified to combine diagnostic and therapeutic capabilities. For ultrasound (US) imaging with polymeric contrast agents, it is necessary to modify the shell to create "stealth" microbubbles but without these modifications sacrificing the agent's ability to interact with the focused US beam. We hypothesize that addition of the classic immune shielding molecule polyethylene glycol (PEG) to a polylactide (PLA) microbubble shell will affect the acoustic and physical properties of the resulting agents. In an effort to determine the best formulation to achieve a balance between stealth and acoustic activity, we compared two PEGylation techniques; addition of increasing amounts of PEG-PLA copolymer and employing incorporation of a PEG lipid (LipidPEG) into the shell. Loss of acoustic enhancement occurred in a dose dependent manner for both types of PEGylated agents (loss of signal occurred at >5 wt% PEG-PLA and >1 wt% LipidPEG), while immune activation was also reduced in a dose-dependent manner for the PEG-PLA agents. This study shows that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with both PEGylation methods, and was best achieved using for PEG-PLA at 5 wt% and for LipidPEG at 1 wt%. Studies are ongoing to evaluate the best method for the targeting and drug delivery capabilities of these agents for applications in cancer treatment. This study represents the basis for understanding the consequences of making modifications to the native polymeric shell. PMID- 27388946 TI - Development of enteric-coated microspheres of embelin for their beneficial pharmacological potential in ulcerative colitis. AB - The aim of the present study is to develop embelin-loaded enteric-coated microspheres and investigate their pharmacological potential in acetic acid induced ulcerative colitis. The optimized formulation of embelin-loaded microspheres has shown significant sustained release of embelin. Further this formulation significantly reduced the ulcer activity score and oxidative stress, and attenuated the inflammatory changes. Thus it may be concluded that embelin loaded enteric-coated microspheres have shown delayed release capacity than plain embelin and exerts colon ulcer protective effect in rats. PMID- 27388947 TI - Results of clubfoot treatment after manipulation and casting using the Ponseti method: experience in Harare, Zimbabwe. AB - OBJECTIVES: The objective of this study was to evaluate the outcomes of the Ponseti manipulation and casting method for clubfoot in a tertiary hospital in Zimbabwe and explore predictors of these outcomes. METHODS: A cohort study included children with idiopathic clubfoot managed from 2011 to 2013 at Parirenyatwa Hospital. Demographic data, clinical features and treatment outcomes were extracted from clinic records. The primary outcome measure was the final Pirani score (clubfoot severity measure) after manipulation and casting. Secondary outcomes included change in Pirani score (pre-treatment to end of casting), number of casts for correction, proportion receiving tenotomy and proportion lost to follow up. RESULTS: A total of 218 children (337 feet) were eligible for inclusion. The median age at treatment was 8 months; 173 children (268 feet) completed casting treatment within the study period. The mean length of time for corrective treatment was 10.2 weeks (9.5-10.9 weeks). Of the 45 children who did not complete treatment, 28 were under treatment and 17 were lost to follow up. A Pirani score of 1 or less was achieved in 85% of feet. Mean Pirani score at presentation was 3.80 (SD 1.15) and post-treatment 0.80 (SD 0.56, P-value <0.0001). Severity of deformity and being male were associated with a higher (worse) final Pirani score. Severity and age over two were associated with an increase in the number of casts required to correct deformity. CONCLUSION: This case series demonstrates that the majority (80%+) of children with clubfoot can achieve a good outcome with the Ponseti manipulation and casting method. PMID- 27388950 TI - Correction: Determination of Kamlet-Taft parameters for selected solvate ionic liquids. AB - Correction for 'Determination of Kamlet-Taft parameters for selected solvate ionic liquids' by Daniel J. Eyckens et al., Phys. Chem. Chem. Phys., 2016, 18, 13153-13157. PMID- 27388948 TI - Positron spectroscopy of point defects in the skyrmion-lattice compound MnSi. AB - Outstanding crystalline perfection is a key requirement for the formation of new forms of electronic order in a vast number of widely different materials. Whereas excellent sample quality represents a standard claim in the literature, there are, quite generally, no reliable microscopic probes to establish the nature and concentration of lattice defects such as voids, dislocations and different species of point defects on the level relevant to the length and energy scales inherent to these new forms of order. Here we report an experimental study of the archetypical skyrmion-lattice compound MnSi, where we relate the characteristic types of point defects and their concentration to the magnetic properties by combining different types of positron spectroscopy with ab-initio calculations and bulk measurements. We find that Mn antisite disorder broadens the magnetic phase transitions and lowers their critical temperatures, whereas the skyrmion lattice phase forms for all samples studied underlining the robustness of this topologically non-trivial state. Taken together, this demonstrates the unprecedented sensitivity of positron spectroscopy in studies of new forms of electronic order. PMID- 27388951 TI - Choroidal and macular thickness changes in type 1 diabetes mellitus patients without diabetic retinopathy. AB - OBJECTIVES: To explore choroidal thickness (ChT) and retinal thickness (RT) changes in patients with type 1 diabetes mellitus (DM). METHODS: Sixty patients with Type 1 DM and 60 age- and sex-matched healthy controls were included in this prospective case-control clinical study. All patients underwent a complete ophthalmological examination. ChT of each participant was measured at the fovea and horizontal nasal and temporal quadrants at 500-um intervals to 1500 um from the foveola using spectral-domain optical coherence tomography (SD-OCT). Age, gender, disease duration, serum glycosylated hemoglobin (HbA1c), fasting glucose level, axial length (AL) and refractive error were noted and analyzed. RESULTS: Mean disease duration, mean HbA1c and mean fasting blood glucose in diabetic patients were 6.1+/-2.8 years, (8.9+/-0.9)% and 287.5+/-69.1 mg/dl, respectively. Age, gender, AL, spherical equivalent differences between the patients and subjects were insignificant (p>0.05). Subfoveal ChT, nasal quadrant ChT measurements, temporal 1500 um and mean nasal ChT were significantly lower in diabetic patients (p<0.05 for all). Temporal 500 um and 1000 um ChT measurements, mean temporal ChT, average ChT, central macular thickness and average macular thickness did not differ significantly between the groups (p>0.05 for all). CONCLUSION: This study showed that there is choroidal thinning in young Type 1 diabetic patients with early period of disease duration without diabetic retinopathy nor any other systemic diseases. Choroidal changes in type 1 DM seem to begin at nasal and distal temporal retina. These results need to be verified by larger and longitudinal studies. PMID- 27388949 TI - Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb. AB - Information processing in early sensory regions is modulated by a diverse range of inhibitory interneurons. We sought to elucidate the role of olfactory bulb interneurons called granule cells (GCs) in odor processing by imaging the activity of hundreds of these cells simultaneously in mice. Odor responses in GCs were temporally diverse and spatially disperse, with some degree of non-random, modular organization. The overall sparseness of activation of GCs was highly correlated with the extent of glomerular activation by odor stimuli. Increasing concentrations of single odorants led to proportionately larger population activity, but some individual GCs had non-monotonic relations to concentration due to local inhibitory interactions. Individual dendritic segments could sometimes respond independently to odors, revealing their capacity for compartmentalized signaling in vivo. Collectively, the response properties of GCs point to their role in specific and local processing, rather than global operations such as response normalization proposed for other interneurons. PMID- 27388952 TI - Communication of Ca(2+) signals via tunneling membrane nanotubes is mediated by transmission of inositol trisphosphate through gap junctions. AB - Tunneling membrane nanotubes (TNTs) are thin membrane projections linking cell bodies separated by many micrometers, which are proposed to mediate signaling and even transfer of cytosolic contents between distant cells. Several reports describe propagation of Ca(2+) signals between distant cells via TNTs, but the underlying mechanisms remain poorly understood. Utilizing a HeLa M-Sec cell line engineered to upregulate TNTs we replicated previous findings that mechanical stimulation elicits robust cytosolic Ca(2+) elevations that propagate to surrounding, physically separate cells. However, whereas this was previously interpreted to involve intercellular communication through TNTs, we found that Ca(2+) signal propagation was abolished - even in TNT-connected cells - after blocking ATP-mediated paracrine signaling with a cocktail of extracellular inhibitors. To then establish whether gap junctions may enable cell-cell signaling via TNTs under these conditions, we expressed sfGFP-tagged connexin-43 (Cx43) in HeLa M-Sec cells. We observed robust communication of mechanically evoked Ca(2+) signals between distant but TNT-connected cells, but only when both cells expressed Cx43. Moreover, we also observed communication of Ca(2+) signals evoked in one cell by local photorelease of inositol 1,4,5-trisphosphate (IP3). Ca(2+) responses in connected cells began after long latencies at intracellular sites several microns from the TNT connection site, implicating intercellular transfer of IP3 and subsequent IP3-mediated Ca(2+) liberation, and not Ca(2+) itself, as the mediator between TNT-connected, Cx43-expressing cells. Our results emphasize the need to control for paracrine transmission in studies of cell-cell signaling via TNTs and indicate that, in this cell line, TNTs do not establish cytosolic continuity between connected cells but rather point to the crucial importance of connexins to enable communication of cytosolic Ca(2+) signals via TNTs. PMID- 27388954 TI - Vertebral artery trauma in a stab wound to the ear: case report. PMID- 27388953 TI - Pulmonary hypertension evaluation by Doppler echocardiogram in children and adolescents with mouth breathing syndrome. AB - INTRODUCTION: Adenotonsillar hyperplasia (ATH) and allergic rhinitis (AR) are the most common causes of upper airway obstruction in children. Such diseases, by affecting the upper airways, can cause chronic alveolar hypoventilation, pulmonary vasoconstriction and pulmonary hypertension, which in some cases, are irreversible. OBJECTIVE: This cross-sectional study aimed to evaluate the prevalence of pulmonary hypertension in two groups of mouth-breathing (MB) 2-12 years old children with ATH and isolated allergic rhinitis, through Doppler echocardiography. METHODS: 54 patients with ATH and indications for adenoidectomy and/or tonsillectomy and 24 patients with persistent allergic rhinitis were selected and submitted to Doppler echocardiography. The Systolic Pulmonary Artery Pressure (SPAP) was determined by tricuspid regurgitation and the Mean Pulmonary Artery Pressure (MPAP) was calculated from the SPAP. Similar measurements were carried out in 25 nasal breathing (NB) individuals. RESULTS: The mean MPAP and SPAP were higher in the MB than in the NB group (17.62+/-2.06 [ATH] and 17.45+/ 1.25 [AR] vs. 15.20+/-2.36 [NB] mmHg, p<0.005, and 25.61+/-3.38 [ATH] and 25.33+/ 2.06 [AR] vs. 21.64+/-3.87 [NB] mmHg, p<0.005, respectively) and the mean acceleration time of pulmonary flow trace (Act) was higher in the NB than in the MB group (127.24+/-12.81 [RN] vs. 114.06+/-10.63ms [ATH] and 117.96+/-10.28 [AR] MS [AR]; p<0.0001). CONCLUSION: None of the MB children (ATH and AR) met the PH criteria, although individuals with both ATH and isolated AR showed significant evidence of increased pulmonary artery pressure by Doppler echocardiography in relation to NB individuals. No differences were observed between the ATH and AR groups. PMID- 27388955 TI - Rhinitis as an associated factor for anxiety and depression amongst adults. AB - INTRODUCTION: Anxiety and depression are frequent disorders of chronic diseases, yet there is no conclusive information to their association with rhinitis. OBJECTIVE: The objective is to determine the frequency of anxiety and depression and its possible association to allergic rhinitis (AR) and non-allergic rhinitis (NAR). METHODS: This is a cross-sectional study in which procured subjects with AR (n=111), NAR (n=34) and a control group (n=96) from the university hospital. The presence of anxiety and depression was considered when it reached a score>13 based on The Beck Anxiety Inventory Test and The Beck Depression Inventory II Test, respectively. The association between AR and NAR with anxiety and depression was adjusted with the Mantel-Haenszel Method and logistic regression. RESULTS: The frequency for anxiety in AR, NAR and the control group was 45.9%, 52.9%, 10.4%, respectively (p<0.001); depression frequency was 38.7%, 47.1%, 16.6% (p=0.0003), respectively. Both AR and NAR were associated to anxiety and depression in women, but not to men. After adjusting the sex: AR was associated to anxiety (OR=5.7, p<0.001) and depression (OR=2.5, p=0.015), while NAR was also associated to anxiety (OR=7.8, p<0.001) and depression (OR=3.3, p<0.014). In multivariate analysis it was identified that AR, NAR and the individual's sex (women) were factors associated to anxiety and depression. Results showed that age was only associated to anxiety. CONCLUSION: AR and NAR are diseases associated to anxiety and depression, at least in women. PMID- 27388956 TI - Comparison of drug-induced sleep endoscopy and Muller's maneuver in diagnosing obstructive sleep apnea using the VOTE classification system. AB - INTRODUCTION: Knowledge of the site of obstruction and the pattern of airway collapse is essential for determining correct surgical and medical management of patients with Obstructive Sleep Apnea Syndrome (OSAS). To this end, several diagnostic tests and procedures have been developed. OBJECTIVE: To determine whether drug-induced sleep endoscopy (DISE) or Muller's maneuver (MM) would be more successful at identifying the site of obstruction and the pattern of upper airway collapse in patients with OSAS. METHODS: The study included 63 patients (52 male and 11 female) who were diagnosed with OSAS at our clinic. Ages ranged from 30 to 66 years old and the average age was 48.5 years. All patients underwent DISE and MM and the results of these examinations were characterized according to the region/degree of obstruction as well as the VOTE classification. The results of each test were analyzed per upper airway level and compared using statistical analysis (Cohen's kappa statistic test). RESULTS: There was statistically significant concordance between the results from DISE and MM for procedures involving the anteroposterior (73%), lateral (92.1%), and concentric (74.6%) configuration of the velum. Results from the lateral part of the oropharynx were also in concordance between the tests (58.7%). Results from the lateral configuration of the epiglottis were in concordance between the tests (87.3%). There was no statistically significant concordance between the two examinations for procedures involving the anteroposterior of the tongue (23.8%) and epiglottis (42.9%). CONCLUSION: We suggest that DISE has several advantages including safety, ease of use, and reliability, which outweigh MM in terms of the ability to diagnose sites of obstruction and the pattern of upper airway collapse. Also, MM can provide some knowledge of the pattern of pharyngeal collapse. Furthermore, we also recommend using the VOTE classification in combination with DISE. PMID- 27388957 TI - Magnet dislocation during 3T magnetic resonance imaging in a pediatric case with cochlear implant. PMID- 27388958 TI - Infantile wryneck: report of 2 cases. PMID- 27388961 TI - Isn't the space-charge potential in ceria-based solid electrolytes largely overestimated? AB - The effective ionic conductivity of polycrystalline solid electrolytes that conduct oxide ions or protons is known to be markedly below those of the corresponding single crystals due to substantial current obstruction across the grain boundary. Numerous studies have previously demonstrated that the ionic charge carriers deplete in the vicinity of the grain boundary to form a potential barrier at the grain boundary, which further impedes the current across the grain boundary. Hence an accurate estimation of the barrier height is essential to acquire a comprehensive and precise mechanistic picture of the ionic current in solid electrolytes. The values of the potential barrier height, i.e. equivalent to the equilibrium space-charge potential with the opposite sign, in prominent solid electrolytes such as ceria solid solutions are available in the literature and were determined exclusively from the ratio of the resistivity of the grain boundary to that of the crystal interior. Here I present the results clearly demonstrating that the resistivity ratio yields considerable overestimation of the barrier height even in relatively diluted solid solutions of ceria. These results imply that the space charge is unlikely the sole origin of the large current obstruction across the grain boundary in ceria-based solid electrolytes. PMID- 27388960 TI - Pain catastrophizing and trunk muscle activation during walking in patients with chronic low back pain. AB - It has been hypothesized that individuals with low back pain (LBP) will have higher trunk muscle activity during gait, in an attempt to limit spine motion, and that this "guarding strategy" may be influenced by the person's psychological response to pain. This study investigated whether the amplitude of trunk muscle activation differs between persons with chronic LBP and healthy individuals during walking, and whether changes in muscle activation were related to pain catastrophizing. Thirty persons with chronic non-specific LBP, stratified into 2 groups of high (HLBP) and low (LLBP) pain catastrophizing, were contrasted with a control group of 15 healthy individuals during walking on a treadmill at a self selected speed. Surface electromyographic (EMG) data were recorded from 10 trunk muscles. The effects of Group and gait Sub-phase on EMG activation amplitudes were assessed. The HLBP group exhibited higher activation of certain muscles throughout the gait cycle, and reduced variability of others at specific sub phases of gait. A significant correlation was found between activation amplitude and pain catastrophizing in most muscles, when controlling for gait speed and pain intensity. These data indicate that altered trunk muscle activation is present in some patients with LBP during walking, but does not represent a universal increase in activation for all muscles. This altered neuromotor control is, however, more strongly associated with pain catastrophizing than with pain intensity, and appears to represent a non-functional, maladaptive behavior, as it alters the normal, phasic pattern of activation in certain trunk muscles. PMID- 27388959 TI - Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis. AB - Angiogenesis is an essential physiological process and an important factor in disease pathogenesis. However, its exploitation as a clinical target has achieved limited success and novel molecular targets are required. Although heme oxygenase 1 (HO-1) acts downstream of vascular endothelial growth factor (VEGF) to modulate angiogenesis, knowledge of the mechanisms involved remains limited. We set out identify novel HO-1 targets involved in angiogenesis. HO-1 depletion attenuated VEGF-induced human endothelial cell (EC) proliferation and tube formation. The latter response suggested a role for HO-1 in EC migration, and indeed HO-1 siRNA negatively affected directional migration of EC towards VEGF; a phenotype reversed by HO-1 over-expression. EC from Hmox1(-/-) mice behaved similarly. Microarray analysis of HO-1-depleted and control EC exposed to VEGF identified cyclins A1 and E1 as HO-1 targets. Migrating HO-1-deficient EC showed increased p27, reduced cyclin A1 and attenuated cyclin-dependent kinase 2 activity. In vivo, cyclin A1 siRNA inhibited VEGF-driven angiogenesis, a response reversed by Ad-HO-1. Proteomics identified structural protein vimentin as an additional VEGF HO-1 target. HO-1 depletion inhibited VEGF-induced calpain activity and vimentin cleavage, while vimentin silencing attenuated HO-1-driven proliferation. Thus, vimentin and cyclins A1 and E1 represent VEGF-activated HO-1-dependent targets important for VEGF-driven angiogenesis. PMID- 27388962 TI - Resistance Exercise in Pregnancy and Outcome. AB - As the health benefits of exercise are increasingly recognized, the traditional advice to rest during pregnancy has changed toward a more healthy and active pregnancy, therefore different forms of exercise have been integrated into the life of the pregnant woman. Although the benefits of using a combination of resistance and aerobic exercises are not yet determined, studies about resistance and strengthen training programs are few although no adverse outcomes were reported. PMID- 27388963 TI - Fetal Heart Rate Response to Maternal Exercise. AB - Current guidelines regarding recommended exercise in pregnancy appear consistent with reported research regarding fetal heart changes in response to maternal exercise. Fetal heart rate increases during pregnancy, but maternal exercise appears well tolerated if performed in uncomplicated pregnancies and not in the supine position. Maximal levels of exercise that are well tolerated by the fetus have not yet been well defined; however, recent literature suggests that sustained exercise during pregnancy may have beneficial effects on autonomic control of fetal heart rate and variability that may lead to long-term health benefits. PMID- 27388965 TI - Different hydroxyapatite magnetic nanoparticles for medical imaging: Its effects on hemostatic, hemolytic activity and cellular cytotoxicity. AB - Magnetic nanoparticles (MNPs) should be highly biocompatible, stable and safely eliminated from the body, and can therefore be successfully used in modern medicine. Synthetic hydroxyapatite (HAP) has well established biocompatible and non-inflammatory properties, as well as a highly stable and flexible structure that allows for an easy incorporation of magnetic ions. This study characterized and compared the in vitro cytotoxicity and hemocompatibility of hydroxyapatite MNPs doped with different ions (Gd(3+/)Fe(2+)/Fe(3+)/Co(2+)). HAP doped with 10% of Gd and Fe(III) presented the highest magnetic moments. Our results showed that Gd doped HAP nanoparticles are non-cytotoxic, hemocompatible, non-hemolytic and non-thrombogenic, in contrast with Fe(III) doped HAP that can be considered thrombogenic. For these reasons we propose that, Gd doped HAP nanoparticles have the most potential for application as a MRI contrast agents. However, use of Fe (III) doped HAP as MRI contrast agents should be further investigated. PMID- 27388964 TI - OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. AB - Bromodomain and extraterminal (BET) bromodomain (BRD) proteins are epigenetic readers that bind to acetylated lysine residues on chromatin, acting as co activators or co-repressors of gene expression. BRD2 and BRD4, members of the BET family, are significantly increased in glioblastoma multiforme (GBM), the most common primary adult brain cancer. OTX015 (MK-8628), a novel BRD2/3/4 inhibitor, is under evaluation in dose-finding studies in solid tumors, including GBM. We investigated the pharmacologic characteristics of OTX015 as a single agent and combined with targeted therapy or conventional chemotherapies in glioblastoma cell lines. OTX015 displayed higher antiproliferative effects compared to its analog JQ1, with GI50 values of approximately 0.2 uM. In addition, C-MYC and CDKN1A mRNA levels increased transiently after 4 h-exposure to OTX015, while BRD2, SESN3, HEXIM-1, HIST2H2BE, and HIST1H2BK were rapidly upregulated and sustained after 24 h. Studies in three additional GBM cell lines supported the antiproliferative effects of OTX015. In U87MG cells, OTX015 showed synergistic to additive activity when administered concomitant to or before SN38, temozolomide or everolimus. Single agent oral OTX015 significantly increased survival in mice bearing orthotopic or heterotopic U87MG xenografts. OTX015 combined simultaneously with temozolomide improved mice survival over either single agent. The passage of OTX015 across the blood-brain barrier was demonstrated with OTX015 tumor levels 7 to 15-fold higher than in normal tissues, along with preferential binding of OTX015 to tumor tissue. The significant antitumor effects seen with OTX015 in GBM xenograft models highlight its therapeutic potential in GBM patients, alone or combined with conventional chemotherapies. PMID- 27388966 TI - Biomimetic nanomaterials: Development of protein coated nanoceria as a potential antioxidative nano-agent for the effective scavenging of reactive oxygen species in vitro and in zebrafish model. AB - Reactive oxygen species (ROS) induced oxidative stress is one of the major factors responsible for initiation of several intracellular toxic events that leads to cell death. Antioxidant enzymes defence system of the body is responsible for maintaining the oxidative balance and cellular homeostasis. Several diseases are promoted by the excessive oxidative stress caused by the impaired antioxidant defence system that leads to oxidant/antioxidant imbalance in the body. In order to restore or precise the aberrant antioxidant system, a large number of catalytic nanoparticles has been screened so far. Exceptional antioxidative activity of nanoceria made it as a potential antioxidative nano agent for the effective scavenging of toxic ROS. In this work albumin coated nanoceria (ANC) was synthesized and further characterised by various physicochemical techniques. The antioxidant and superoxide dismutase (SOD) assay confirm that the albumin coating do not alter the antioxidant potential of ANC. The biocompatibility and protective efficacy of ANC against oxidative stress was investigated both in vitro and in vivo in human lung epithelial (L-132) cells and zebrafish embryos, respectively. The inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy (TEM) and field emission scanning electron microscope (FE-SEM) analysis corroborates the uptake of ANC by the cells. Furthermore, the semi-quantitative gene expression studies confirmed that the ANC successfully defend the cells against oxidative stress by preserving the antioxidant system of the cells. Thus, the current work open up a new avenue for the development of improved antioxidant nano-drug therapies. PMID- 27388967 TI - Novel cell-penetrating peptide-loaded nanobubbles synergized with ultrasound irradiation enhance EGFR siRNA delivery for triple negative Breast cancer therapy. AB - The lack of safe and effective gene delivery strategies remains a bottleneck for cancer gene therapy. Here, we describe the synthesis, characterization, and application of cell-penetrating peptide (CPP)-loaded nanobubbles (NBs), which are characterized by their safety, strong penetrating power and high gene loading capability for gene delivery. An epidermal growth factor receptor (EGFR)-targeted small interfering RNA (siEGFR) was transfected into triple negative breast cancer (TNBC) cells via prepared CPP-NBs synergized with ultrasound-targeted microbubble destruction (UTMD) technology. Fluorescence microscopy showed that siEGFR and CPP were loaded on the shells of the NBs. The transfection efficiency and cell proliferation levels were evaluated by FACS and MTT assays, respectively. In addition, in vivo experiments showed that the expression of EGFR mRNA and protein could be efficiently downregulated and that the growth of a xenograft tumor derived from TNBC cells could be inhibited. Our results indicate that CPP-NBs carrying siEGFR could potentially be used as a promising non-viral gene vector that can be synergized with UTMD technology for efficient TNBC therapy. PMID- 27388968 TI - A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release. AB - A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl) imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and pi-pi interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release. PMID- 27388970 TI - The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients. AB - INTRODUCTION: Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual responses to drug treatments. AREAS COVERED: The various responses to pharmacological agents are mainly determined by the different types of genetic variants of the CYP450. CYP2D6 polymorphism is well known for its variation in the metabolism of drugs from many therapeutic arenas, including some analgesic drugs such as codeine, hydromorphone, oxycodone and tramadol. Allele combinations determine the phenotypic expression, characterized as either: extensive metabolizer, intermediate metabolizer, ultra-rapid metabolizer and poor metabolizer. EXPERT OPINION: The Human Genome Project (HGP) revolutionized the future of medicine and the way health care providers approach individualized patient treatment, and chronic pain management is one of those areas. The key findings in the literature appear to be related to the CYP2D6 expression and its high polymorphism influencing the metabolism of opioid medications, and the impact of that on the patient's therapeutic outcome thus exemplifying the importance of genetic testing for CYP2D6 in the process of physician therapeutic decision making. PMID- 27388969 TI - Microfluidic fabrication of polymersomes enclosing an active Belousov-Zhabotinsky (BZ) reaction: Effect on their stability of solute concentrations in the external media. AB - Core/shell double emulsions were fabricated using glasscapillary based microfluidic techniques. Poly(butadiene) 46-bpoly(ethylene oxide)30 in mixture with cyclo-hexane/chloroform were contained as the shell part of droplets, whose core part was the full 1,4-cyclohexadiene based Belousov-Zhabotinsky reaction solution of unknown osmolality. The droplets were collected in solutions of both low and relatively high concentrations of salt. This resulted in the respective increase or decrease of the core part diameter. In both cases, after an incubation period, the droplets eventually evolved into polymer vesicles. In solutions with low concentration of salt, the droplets evolved into polymer vesicles after the evaporation of the vola-tile solvent contained in the shell part. Due to the dewetting of the shell and core parts,droplets in solutions of relatively high salt concentration evolved into polymer vesicles only after three days of incubation. The dewetted shell part displayed crescent-moon-shapes with different curvatures. The final diameter of the vesicles differed from the diameter of the initial core droplets. We demonstrate that vesicles with unknown osmolality core parts are formed in both solutions of very low or relatively high concentration of salt; furthermore, we also demonstrate that they follow different formation pathways. In the appropriate conditions, the vesicles experienced a form of "collapsing" behavior due to the activity of the entrapped chemical reaction. PMID- 27388971 TI - Analysis of lower limb work-energy patterns in world-class race walkers. AB - The aim of this study was to analyse lower limb work patterns in world-class race walkers. Seventeen male and female athletes race walked at competitive pace. Ground reaction forces (1000 Hz) and high-speed videos (100 Hz) were recorded and normalised joint moments, work and power, stride length, stride frequency and speed estimated. The hip flexors and extensors were the main generators of energy (24.5 J (+/-6.9) and 40.3 J (+/-8.3), respectively), with the ankle plantarflexors (16.3 J (+/-4.3)) contributing to the energy generated during late stance. The knee generated little energy but performed considerable negative work during swing (-49.1 J (+/-8.7)); the energy absorbed by the knee extensors was associated with smaller changes in velocity during stance (r = .783, P < .001), as was the energy generated by the hip flexors (r = -.689, P = .002). The knee flexors did most negative work (-38.6 J (+/-5.8)) and the frequent injuries to the hamstrings are probably due to this considerable negative work. Coaches should note the important contributions of the hip and ankle muscles to energy generation and the need to develop knee flexor strength in reducing the risk of injury. PMID- 27388972 TI - Auricular epithesis. PMID- 27388973 TI - Relationship between self-reported and objectively measured physical activity and subjective memory impairment in breast cancer survivors: role of self-efficacy, fatigue and distress. AB - PURPOSE: Many breast cancer survivors report cancer and cancer treatment associated cognitive change. However, very little is known about the relationship between physical activity and subjective memory impairment (SMI) in this population. The purpose of this study is to examine the relationship between physical activity and SMI and longitudinally test a model examining the role of self-efficacy, fatigue and distress as potential mediators. METHODS: Post treatment breast cancer survivors (N = 1477) completed measures of physical activity, self-efficacy, distress (depression, concerns about recurrence, perceived stress, anxiety), fatigue and SMI at baseline and 6-month follow-up. A subsample (n = 362) was randomly selected to wear an accelerometer. It was hypothesized that physical activity indirectly influences SMI via exercise self efficacy, distress and fatigue. Relationships were examined using panel analysis within a covariance modeling framework. RESULTS: The hypothesized model provided a good fit in the full sample (chi2 = 1462.5, df = 469, p = <0.001; CFI = 0.96; SRMR = 0.04) and the accelerometer subsample (chi2 = 961.8, df = 535, p = <0.001, CFI = 0.94, SRMR = 0.05) indicating increased physical activity is indirectly associated with reduction in SMI across time, via increased exercise self efficacy and reduced distress and fatigue. CONCLUSIONS: Higher levels of physical activity, lower levels of fatigue and distress and higher exercise self-efficacy may play an important role in understanding SMI in breast cancer survivors across time. Future research is warranted to replicate and explore these relationships further. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27388975 TI - A study of the mechanical properties of ePTFE suture used as artificial mitral chordae. AB - BACKGROUND AND AIM OF THE STUDY: We investigated the dimensional and mechanical properties of polyetetrafluorene (ePTFE) sutures used as artificial chordae during mitral valve repair. METHODS: Mechanical properties of ePTFE synthetic chordae tendineae were tested with a servo hydraulic testing machine. Several different lengths from 2 to 14 cm were studied under both single and multiple mechanical traction. RESULTS: The mechanical behavior of artificial chordae reveals that three centimeters is the length over which we observe a significant increase in stiffness. The chordae stiffness grows further at the length greater than seven centimeters following a low number of traction cycles. CONCLUSION: The increase of the length of artificial ePTFE chordae is accompanied by an increasing stiffness that compromises the long-term resistance of the chordae. ePTFE length can alter the performance of artificial chordae. This suggests that mitral valve repairs which anchor ePTFE neochordae to the ventricular apex may have less durability than when anchored to the tips of the papillary muscles. PMID- 27388974 TI - Efficient and safe gene delivery to human corneal endothelium using magnetic nanoparticles. AB - AIM: To develop a safe and efficient method for targeted, anti-apoptotic gene therapy of corneal endothelial cells (CECs). MATERIALS & METHODS: Magnetofection (MF), a combination of lipofection with magnetic nanoparticles (MNPs; PEI-Mag2, SO-Mag5, PalD1-Mag1), was tested in human CECs and in explanted human corneas. Effects on cell viability and function were investigated. Immunocompatibility was assessed in human peripheral blood mononuclear cells. RESULTS: Silica iron-oxide MNPs (SO-Mag5) combined with X-tremeGENE-HP achieved high transfection efficiency in human CECs and explanted human corneas, without altering cell viability or function. Magnetofection caused no immunomodulatory effects in human peripheral blood mononuclear cells. Magnetofection with anti-apoptotic P35 gene effectively blocked apoptosis in CECs. CONCLUSION: Magnetofection is a promising tool for gene therapy of corneal endothelial cells with potential for targeted on-site delivery. PMID- 27388976 TI - A nanometric Rh overlayer on a metal foil surface as a highly efficient three-way catalyst. AB - Pulsed arc-plasma (AP) deposition of an Rh overlayer on an Fe-Cr-Al stainless steel foil produced a composite material that exhibited high activity for automotive three-way catalysis (TWC). The AP pulses deposited metallic Rh nanoparticles 1-3 nm in size, whose density on the surface increased with the number of pulses. This led to coalescence and grain growth on the foil surface and the eventual formation of a uniform two-dimensional Rh overlayer. Full coverage of the 51 MUm-thick flat foil by a 3.2 nm-thick Rh overlayer was achieved after 1,000 pulses. A simulated TWC reaction using a miniature honeycomb fabricated using flat and corrugated foils with the Rh overlayers exhibited successful light-off at a practical gaseous hourly space velocity of 1.2 * 10(5) h(-1). The turnover frequency for the NO-CO reaction over the metallic honeycomb catalyst was ca. 80-fold greater than that achieved with a reference Rh/ZrO2 coated cordierite honeycomb prepared using a conventional wet impregnation and slurry coating procedure. Despite the nonporosity and low surface area of the foil-supported Rh overlayer compared with conventional powder catalysts (Rh/ZrO2), it is a promising alternative design for more efficient automotive catalysts that use less Rh loading. PMID- 27388977 TI - Genetic evaluation of English bulldogs with cystine uroliths. PMID- 27388979 TI - Attention in the predictive mind. AB - It has recently become popular to suggest that cognition can be explained as a process of Bayesian prediction error minimization. Some advocates of this view propose that attention should be understood as the optimization of expected precisions in the prediction-error signal (Clark, 2013, 2016; Feldman & Friston, 2010; Hohwy, 2012, 2013). This proposal successfully accounts for several attention-related phenomena. We claim that it cannot account for all of them, since there are certain forms of voluntary attention that it cannot accommodate. We therefore suggest that, although the theory of Bayesian prediction error minimization introduces some powerful tools for the explanation of mental phenomena, its advocates have been wrong to claim that Bayesian prediction error minimization is 'all the brain ever does'. PMID- 27388980 TI - Influence of intraoperative remifentanil and sufentanil on sensory perception: a randomized trial. AB - OBJECTIVE: The clinical relevance of pro- and hyperalgesic effects of opioids is still a matter of debate. Particularly for remifentanil, an increased postoperative need for analgesics has been demonstrated suggesting opioid-induced hyperalgesia as a possible cause. The aim of the study was therefore to investigate the effect of intraoperatively applied remifentanil compared to sufentanil on somatosensory thresholds investigated with the quantitative sensory testing (QST) battery of the German Research Network on Neuropathic Pain (DFNS). RESEARCH DESIGN AND METHODS: Twenty-three patients undergoing surgery of the female breast were randomly assigned to intraoperative remifentanil (0.4 MUg * kg 1 * min-1) or sufentanil (0.25 MUg * kg-1 bolus, 0.15 MUg * kg-1, repetition after 60 min) application. Anesthesia was maintained BIS-guided (Bispectral indexTM) with propofol and postoperative analgesia was ensured with paracetamol (max. 3 g/24 h). Quantitative sensory testing was performed in the region of dermatome Th 5 in the mid-axillary line preoperatively and 20 h postoperatively. CLINICAL TRIAL REGISTRATION: The study was registered at the German registry for clinical studies (DRKS00009002). MAIN OUTCOME MEASURES: Comparison of somatosensory thresholds before versus after surgery and application of intraoperative remifentanil or sufentanil. RESULTS: Sixteen patients could be finally included in the analysis. No differences of mechanical or thermal detection or pain thresholds were observed between pre- and postoperative testing or between remifentanil and sufentanil. CONCLUSION: A change of somatosensory thresholds or a clinically relevant opioid-induced hyperalgesia in the selected small patient sample (segmental resections or mastectomy with or without sentinel lymph node biopsy, surgery length <90 minutes, sufficient postoperative pain medication with paracetamol due to rather low postoperative pain intensities) with remifentanil or sufentanil was not detected 20 h after surgery. PMID- 27388981 TI - Role of Micronutrients on Dyeing Wastewater Treatment in Activated Sludge Process. AB - Adequate individual supplements of Zn, Co and Mo increased chemical oxygen demand (COD) removal and specific oxygen uptake rates during activated sludge treatment of dyeing wastewater, while overdoses of micronutrients can decrease metabolic rates. The effects of combing Zn, Co, and Mo at different doses were investigated using response surface methodology, with a second order polynomial equation: Y = 78.19+ 0.17X1 + 37.33 X2 + 20.20X3 - 5.58X1X2 - 63.05 X2X3, where Y means COD removal rate (%), X1 means Co concentration, X2 means Zn concentration, X3 means Mo concentration. The maximum COD removal efficiency of 89.41% was achieved with doses of 0.02 mg/L Co, 0.24 mg/L Zn and 0.45 mg/L Mo. Both the combinations of Zn-Co and Zn-Mo acted antagonistically for COD removal efficiency, and the combination of Co-Mo was negligible to COD removal efficiency. Doses of micronutrients, particularly Zn, Co and Mo, were beneficial for microbial shift towards Planctomyces and Bacteroidetes. PMID- 27388982 TI - Heavy metals and essential elements in Italian cereals. AB - Crops intended for human nutrition and food production containing different essential trace elements, such as copper and zinc, could be contaminated by toxic metals like cadmium and lead. The interrelationship between micronutrients and contaminant trace elements in different cereals was investigated in North-western Italy, where both agricultural and industrial activities are present. Elemental concentrations in sampled cereals were assessed by inductively coupled plasma mass spectrometry (ICP-MS). Rice, oats and barley reached the highest median levels for Al, Cd and Pb content, while corn samples were less contaminated by toxic metals. Regarding essential elements highest median values of Cu and Zn were both found in barley, while Ni median content was higher in oats. Rice had the lowest median levels of essential elements. The correlation study between toxic and essential elements seemed to demonstrate fixed trends in analysed samples, corroborating the importance of a different diet to limit potential adverse effects caused by toxic elements. PMID- 27388983 TI - Guidelines: Surgical or medical therapy for patients with obesity and T2DM? PMID- 27388984 TI - NASH: Pioglitazone safe and effective for treating T2DM in patients with NASH. PMID- 27388985 TI - Stem cells: Calorie restriction affects intestinal cells. PMID- 27388986 TI - Adrenal function: No difference between CT and AVS for determining treatment options in primary aldosteronism. PMID- 27388987 TI - The pathophysiology of defective proteostasis in the hypothalamus - from obesity to ageing. AB - Hypothalamic dysfunction has emerged as an important mechanism involved in the development of obesity and its comorbidities, as well as in the process of ageing and age-related diseases, such as type 2 diabetes mellitus, hypertension and Alzheimer disease. In both obesity and ageing, inflammatory signalling is thought to coordinate many of the cellular events that lead to hypothalamic neuronal dysfunction. This process is triggered by the activation of signalling via the toll-like receptor 4 pathway and endoplasmic reticulum stress, which in turn results in intracellular inflammatory signalling. However, the process that connects inflammation with neuronal dysfunction is complex and includes several regulatory mechanisms that ultimately control the homeostasis of intracellular proteins and organelles (also known as 'proteostasis'). This Review discusses the evidence for the key role of proteostasis in the control of hypothalamic neurons and the involvement of this process in regulating whole-body energy homeostasis and lifespan. PMID- 27388988 TI - Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. AB - Diabetes mellitus is one of the most important public health challenges of the twenty-first century. Until the past decade, it has been seriously underrated as a global health threat. Major gaps exist in efforts to comprehend the burden nationally and globally, especially in developing nations, due to a lack of accurate data for monitoring and surveillance. Early attempts to obtain accurate data, discussed in this article, seem to have been cast aside so, at present, these needs remain unmet. Existing international efforts to assemble information fall far short of requirements. Current estimates are imprecise, only providing a rough picture, and probably underestimate the disease burden. The methodologies that are currently used, and that are discussed in this Perspectives article, are inadequate for providing a complete and accurate assessment of the prevalence of diabetes mellitus. International consensus on uniform standards and criteria for reporting national data on diabetes mellitus prevalence as well as for common complications of diabetes mellitus and mortality need to be developed. PMID- 27388989 TI - Diabetes: A metabolomic signature to predict the transition from GDM to T2DM. PMID- 27388990 TI - A novel microcrystalline tyrosine-adsorbed, mite-allergoid subcutaneous immunotherapy: 1-year follow-up report. AB - AIM: A 1-year follow-up study comparing the safety and tolerability of the dosing schedules, satisfaction and effectiveness of a novel microcrystalline tyrosine adsorbed mite (Dermatophagoides pteronyssinus)-allergoid subcutaneous immunotherapy (Acarovac PlusTM) in 30 adult patients (18-65 years) with allergic rhinitis and/or asthma. MATERIALS & METHODS: The effectiveness of the product was assessed by nasal provocation test measuring peak nasal inspiratory flow/symptoms, in vitro immunologic changes (IgE, IgG4 and IL-10) and Treatment Satisfaction Questionnaire for Medication. RESULTS: No adverse events were reported during dosing schedules. Significant decreases in symptom scores and drop of peak nasal inspiratory flow in follow-up visits (4 weeks and 1 year) were recorded. Significant increases in IgG4-specific antibody titers and IL-10 were exhibited. CONCLUSION: Significant decreases in clinical symptoms and immunological parameters were observed, accompanying a high level of patient satisfaction and tolerance. PMID- 27388991 TI - Identification of an S100A8 Receptor Neuroplastin-beta and its Heterodimer Formation with EMMPRIN. AB - We previously reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer, an S100A9 receptor. Here, we identify neuroplastin-beta as an unreported S100A8 receptor. Neuroplastin-beta and extracellular matrix metalloproteinase inducer form homodimers and a heterodimer, and they are co-localized on the surface of cultured normal human keratinocytes. Knockdown of both receptors suppressed cell proliferation and proinflammatory cytokine induction. Upon stimulation with S100A8, neuroplastin-beta recruited GRB2 and activated extracellular signal-regulated kinase, resulting in keratinocyte proliferation. Keratinocyte proliferation in response to inflammatory stimuli was accelerated in involucrin promoter-driven S100A8 transgenic mice. Further, S100A8 and S100A9 were strongly up-regulated and co-localized in lesional skin of atopic dermatitis patients. Our results indicate that neuroplastin-beta and extracellular matrix metalloproteinase inducer form a functional heterodimeric receptor for S100A8/A9 heterodimer, followed by recruitment of specific adaptor molecules GRB2 and TRAF2, and this signaling pathway is involved in activation of both keratinocyte proliferation and skin inflammation in atopic skin. Suppression of this pathway might have potential for treatment of skin diseases associated with chronic inflammation such as atopic dermatitis. PMID- 27388992 TI - PDE4 Inhibition as Potential Treatment of Epidermolysis Bullosa Acquisita. AB - Pemphigoid diseases such as epidermolysis bullosa acquisita (EBA) may be difficult to treat. In pemphigoid diseases, mucocutaneous blistering is caused by autoantibodies to hemidesmosomal antigens; in EBA the autoantigen is type VII collagen. Despite growing insights into pemphigoid disease pathogenesis, corticosteroids are still a mainstay of treatment. In experimental EBA, myeloid cell activation is a key event leading to blistering. Activation of these cells depends on phosphodiesterase (PDE) 4. We therefore evaluated the potential for PDE4 inhibition in EBA: PDE4 was highly expressed in inflammatory cells and in the epidermis of patients compared with healthy skin samples. PDE4 inhibitors rolipram, roflumilast, and roflumilast N-oxide prevented the release of immune complex-induced reactive oxygen species from polymorphonuclear leukocytes and separation of the dermal-epidermal junction of skin incubated with antibodies to collagen type VII and polymorphonuclear leukocytes. The PDE4 inhibitors also impaired CD62L shedding and decreased CD11b expression on immune complex stimulated polymorphonuclear leukocytes. For in vivo validation, experimental EBA was induced in mice by transfer of anti-collagen type VII IgG or immunization with collagen type VII. Roflumilast dose-dependently reduced blistering in antibody transfer-induced EBA and also hindered disease progression in immunization-induced EBA. PDE4 inhibition emerges as a new treatment modality for EBA and possibly other neutrophil-driven pemphigoid diseases. PMID- 27388993 TI - AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production. AB - Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF kappaB activation. We showed that as a consequence, AP1S3-deficient cells up regulate IL-1 signaling and overexpress IL-36alpha, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target. PMID- 27388995 TI - Two-dimensional materials for novel liquid separation membranes. AB - Demand for a perfect molecular-level separation membrane with ultrafast permeation and a robust mechanical property for any kind of species to be blocked in water purification and desalination is urgent. In recent years, due to their intrinsic characteristics, such as a unique mono-atom thick structure, outstanding mechanical strength and excellent flexibility, as well as facile and large-scale production, graphene and its large family of two-dimensional (2D) materials are regarded as ideal membrane materials for ultrafast molecular separation. A perfect separation membrane should be as thin as possible to maximize its flux, mechanically robust and without failure even if under high loading pressure, and have a narrow nanochannel size distribution to guarantee its selectivity. The latest breakthrough in 2D material-based membranes will be reviewed both in theories and experiments, including their current state-of-the art fabrication, structure design, simulation and applications. Special attention will be focused on the designs and strategies employed to control microstructures to enhance permeation and selectivity for liquid separation. In addition, critical views on the separation mechanism within two-dimensional material-based membranes will be provided based on a discussion of the effects of intrinsic defects during growth, predefined nanopores and nanochannels during subsequent fabrication processes, the interlayer spacing of stacking 2D material flakes and the surface charge or functional groups. Furthermore, we will summarize the significant progress of these 2D material-based membranes for liquid separation in nanofiltration/ultrafiltration and pervaporation. Lastly, we will recall issues requiring attention, and discuss existing questionable conclusions in some articles and emerging challenges. This review will serve as a valuable platform to provide a compact source of relevant and timely information about the development of 2D material-based membranes as well as fully explain up-to-date mechanisms and models of water transport and molecular separation behavior, which will arouse great interest among researchers entering or already working in the field of 2D material-based membranes. PMID- 27388994 TI - The Next Generation Non-competitive Active Polyester Nanosystems for Transferrin Receptor-mediated Peroral Transport Utilizing Gambogic Acid as a Ligand. AB - The current methods for targeted drug delivery utilize ligands that must out compete endogenous ligands in order to bind to the active site facilitating the transport. To address this limitation, we present a non-competitive active transport strategy to overcome intestinal barriers in the form of tunable nanosystems (NS) for transferrin receptor (TfR) utilizing gambogic acid (GA), a xanthanoid, as its ligand. The NS made using GA conjugated poly(lactide-co glycolide) (PLGA) have shown non-competitive affinity to TfR evaluated in cell/cell-free systems. The fluorescent PLGA-GA NS exhibited significant intestinal transport and altered distribution profile compared to PLGA NS in vivo. The PLGA-GA NS loaded with cyclosporine A (CsA), a model peptide, upon peroral dosing to rodents led to maximum plasma concentration of CsA at 6 h as opposed to 24 h with PLGA-NS with at least 2-fold higher levels in brain at 72 h. The proposed approach offers new prospects for peroral drug delivery and beyond. PMID- 27388996 TI - The Use of Iliac Side Branch Devices in Patients with Aortoiliac Aneurysm. AB - PURPOSE: The aim of this study was to evaluate the technical feasibility and short-time patency rate of iliac side branch devices based on the authors' institution's experience. MATERIALS AND METHODS: Data of 17 patients (all men) with an aortoiliac aneurysm (median age 72.5 years) who underwent endovascular repair between October 2013 and June 2015 (20 months) at our institution was analyzed retrospectively. Primary endpoint was primary technical success, defined as adequate implantation of the iliac branch device with patency of the hypogastric side branch without the need of further re-interventions within 30 days. Mean follow-up was 8.2 +/- 5.4 months. RESULTS: Eighteen iliac side branch devices were implanted with a branch patency of 100 % and a primary technical success rate of 94.4 % (n = 17). Perioperative 30 days mortality was 0 %. The mean diameter of treated abdominal aorta and common iliac artery was 41 +/- 14 and 30 +/- 8 mm. In one case partial dislocation of the iliac side branch device occurred due to severe kinking of iliac arteries with development of an iliac endoleak type Ib that had to be treated in a second intervention. Three patients (15 %) showed an endoleak type II from the inferior mesenteric artery without the need of re-intervention. After three months one patient suffered from subtotal thrombotic occlusion of the bridging stent that was successfully resolved through intra-arterial fibrinolytic therapy and additional stent graft implantation. CONCLUSION: Summarized, implantation of iliac side branch devices is a feasible technique with favourable short-term results in patients with aortoiliac aneurysm. KEY POINTS: * Implantation of iliac side branch devices is a feasible technique.* Distinguish short-term results of side branch endografting in patients with aortoiliac aneurysm.* Carefully patient selection is necessary to avoid complications and re-interventions. Citation Format: * Maus V, Kurz P, Sommer CM et al. The Use of Iliac Side Branch Devices in Patients with Aortoiliac Aneurysm.. Fortschr Rontgenstr 2016; 188: 746 - 752. PMID- 27388997 TI - Detection of methaemoglobinaemia and its application in 'poppers' abuse: maintaining the right balance between reduction and autooxidation during storage. AB - In our study, we analysed the effect of a variety of storage conditions on the methaemoglobin (MetHb) content of blood samples obtained from altogether 110 deceased subjects with diverse causes of death, including three 'poppers'-related fatalities. The obtained results were compared to data from blood samples of six living, healthy subjects. Results obtained from the spectrophotometric measurement of blood MetHb content suggest that storage at room temperature (RT) and storage at -20 degrees C result in either highly fluctuating values, as was the case for the RT samples, or values much higher than the initial MetHb concentrations when stored at -20 degrees C. Blood samples at 4 degrees C showed more stable MetHb levels, which, however, increased with up to 4 % of the initial value after only 3 weeks of storage. These factors pose a problem in forensic toxicology, especially in nitrite abuse cases, where the involvement of such substance abuse is often unknown at the time of blood sampling and thus often requires longer storage times. Nevertheless, even after the storage of blood samples over several months at 4 and -20 degrees C, 'poppers' cases still show a significantly higher MetHb concentration as compared to non-'poppers' samples that were stored for the same time period under identical conditions. PMID- 27388998 TI - Are sertraline, paroxetine and duloxetine the most effective antidepressants for use in depressed adults over 60 years? PMID- 27388999 TI - Prevention and treatment of mental health crises: examining the gaps in the evidence base. PMID- 27389000 TI - Measurement variability of the TearLab Osmolarity System. AB - PURPOSE: To independently assess the measurement variability of TearLab System in a clinical setting of one visit and to estimate the minimum number of measurements required for reliable readings of tear osmolarity. METHODS: Ten consecutive osmolarity measurements were taken from both eyes by the same examiner at one visit for fourteen subjects. The ocular surface disease index symptoms questionnaire and tear film break up time were also performed. Group average cumulative mean and cumulative coefficient of variation were calculated to assess the TearLab measurement variation. Repeated application of Thompson's tau method was performed to identify the outliers in tear osmolarity readings for each eye. Results from both eyes were analysed separately. RESULTS: Up to two randomly occurring outlying values in 10 consecutive measurements were found in 19 out of 28 measured eyes. No statistically significant differences between the left and right eye were found for the group mean and group standard deviation (paired t-test, p=0.099 and p=0.068, respectively), however the cumulative coefficient of variation indicated higher measurement group variability on one eye. Estimated cumulative coefficient of variation indicated the minimum of three consecutive acquisitions required for the measurement to be reliable. CONCLUSIONS: TearLab Osmolarity System required at least three consecutive measurements to be taken in order to provide clinically reliable tear osmolarity readings. Also, taking the maximum osmolarity value for detecting dry eye disease should be viewed with caution since outlying readings of tear osmolarity frequently occur. PMID- 27389002 TI - Low-level lead exposure changes endothelial modulation in rat resistance pulmonary arteries. AB - Lead exposure induces hypertension and endothelial dysfunction. However, the effects on the pulmonary vasculature have not been explored. In this study, rats exposed to lead acetate for seven days (4MUg/100g on the 1st day and 0.05MUg/100g/day i.m. subsequently) had lead blood level of 3.9+/-0.7MUg/dL and increased right ventricular pressures. There was an increased Pb deposition and superoxide anions production in the pulmonary arteries, associated with reduced vasoconstriction but unchanged endothelium-dependent vasodilatation to acetylcholine (ACh). In both groups, inhibition of the nitric oxide (NO) synthase with L-NAME blocked the response to ACh, while indomethacin (cycloxygenase inhibitor) had no effect. Incubation with nonspecific potassium channel blocker (tetraethylammonium) reduced the ACh-induced vasodilatation only in the Pb group. Apamin (SKCa channel blocker) and 4-aminopyridine (Kv channel blocker), but not iberiotoxin (BKCa channel blocker), also inhibited this response in the Pb group. The vasodilatation to exogenous NO was reduced by Pb, while relaxation to the cGMP analogue was similar between groups. Concordantly, the protein level of soluble guanylate cyclase (sGC) was reduced. In conclusion, short-term and low level exposure to Pb changes pulmonary haemodynamic and increases oxidative stress. The pulmonary vasculature exhibited increased hyperpolarization by the Kv and SKCa channels, probably as a compensatory mechanism to the decreased responsiveness to NO. PMID- 27389001 TI - Bone loss and vascular calcification: A bi-directional interplay? AB - Vascular calcification (VC) represents a recognized adverse predictor for cardiovascular morbidity and mortality. Previously considered passive and degenerative, VC is now recognized as an active process that resembles bone formation, and shares a number of histopathological features, mineral composition, and initiation mechanisms with bone development and metabolism. Oxidative stress and inflammation are key factors in both VC and osteoporosis (OP). Biochemical factors known to be primarily involved in the healthy bone metabolism also regulate VC. These biomarkers include vitamin D, osteoprotegerin, osteopontin, matrix Gla protein, cathepsin K, fibroblast growth factor-23, and fetuin-A. A better understanding of this highly controlled regulatory network, with multiple, nested feedback loops and cross talk between organs, may help to decrease the growing prevalence of calcific vasculopathy as well as OP in the aging population, and to advance in common preventive and therapeutic interventions targeted at both conditions. PMID- 27389003 TI - Preventive and Abortive Strategies for Stimulation Based Control of Epilepsy: A Computational Model Study. AB - Epilepsy is a condition in which periods of ongoing normal EEG activity alternate with periods of oscillatory behavior characteristic of epileptic seizures. The dynamics of the transitions between the two states are still unclear. Computational models provide a powerful tool to explore the underlying mechanisms of such transitions, with the purpose of eventually finding therapeutic interventions for this debilitating condition. In this study, the possibility to postpone seizures elicited by a decrease of inhibition is investigated by using external stimulation in a realistic bistable neuronal model consisting of two interconnected neuronal populations representing pyramidal cells and interneurons. In the simulations, seizures are induced by slowly decreasing the conductivity of GABA[Formula: see text] synaptic channels over time. Since the model is bistable, the system will change state from the initial steady state (SS) to the limit cycle (LS) state because of internal noise, when the inhibition falls below a certain threshold. Several state-independent stimulations paradigms are simulated. Their effectiveness is analyzed for various stimulation frequencies and intensities in combination with periodic and random stimulation sequences. The distributions of the time to first seizure in the presence of stimulation are compared with the situation without stimulation. In addition, stimulation protocols targeted to specific subsystems are applied with the objective of counteracting the baseline shift due to decreased inhibition in the system. Furthermore, an analytical model is used to investigate the effects of random noise. The relation between the strength of random noise stimulation, the control parameter of the system and the transitions between steady state and limit cycle are investigated. The study shows that it is possible to postpone epileptic activity by targeted stimulation in a realistic neuronal model featuring bistability and that it is possible to stop seizures by random noise in an analytical model. PMID- 27389004 TI - Multi-Biosignal Analysis for Epileptic Seizure Monitoring. AB - Persons who suffer from intractable seizures are safer if attended when seizures strike. Consequently, there is a need for wearable devices capable of detecting both convulsive and nonconvulsive seizures in everyday life. We have developed a three-stage seizure detection methodology based on 339 h of data (26 seizures) collected from 10 patients in an epilepsy monitoring unit. Our intent is to develop a wearable system that will detect seizures, alert a caregiver and record the time of seizure in an electronic diary for the patient's physician. Stage I looks for concurrent activity in heart rate, arterial oxygenation and electrodermal activity, all of which can be monitored by a wrist-worn device and which in combination produce a very low false positive rate. Stage II looks for a specific pattern created by these three biosignals. For the patients whose seizures cannot be detected by Stage II, Stage III detects seizures using limited channel electroencephalogram (EEG) monitoring with at most three electrodes. Out of 10 patients, Stage I recognized all 11 seizures from seven patients, Stage II detected all 10 seizures from six patients and Stage III detected all of the seizures of two out of the three patients it analyzed. PMID- 27389005 TI - Cerebral Critical Closing Pressure: Is the Multiparameter Model Better Suited to Estimate Physiology of Cerebral Hemodynamics? AB - BACKGROUND: Cerebral critical closing pressure (CrCP) is the level of arterial blood pressure (ABP) at which small brain vessels close and blood flow stops. This value is always greater than intracranial pressure (ICP). The difference between CrCP and ICP is explained by the tone of the small cerebral vessels (wall tension). CrCP value is used in several dynamic cerebral autoregulation models. However, the different methods for calculation of CrCP show frequent negative values. These findings are viewed as a methodological limitation. We intended to evaluate CrCP in patients with severe traumatic brain injury (TBI) with a new multiparameter impedance-based model and compare it with results found earlier using a transcranial Doppler (TCD)-ABP pulse waveform-based method. METHODS: Twelve severe TBI patients hospitalized during September 2005-May 2007. Ten men, mean age 32 years (16-61). Four had decompressive craniectomies (DC); three presented anisocoria. Patients were monitored with TCD cerebral blood flow velocity (FV), invasive ABP, and ICP. Data were acquired at 50 Hz with an in house developed data acquisition system. We compared the earlier studied "first harmonic" method (M1) results with results from a new recently developed (M2) "multiparameter method." RESULTS: M1: In seven patients CrCP values were negative, reaching -150 mmHg. M2: All positive values; only one lower than ICP (ICP 60 mmHg/ CrCP 57 mmHg). There was a significant difference between M1 and M2 values (M1 < M2) and between ICP and M2 (M2 > ICP). CONCLUSION: M2 results in positive values of CrCP, higher than ICP, and are physiologically interpretable. PMID- 27389006 TI - Neurology Education for Critical Care Fellows Using High-Fidelity Simulation. AB - BACKGROUND: Simulation is becoming a more common modality in medical education. The data regarding effectiveness of simulation in critical care neurology education are limited. METHODS: We administered a three-scenario simulation course to critical care fellowship trainees at a large academic medical center as a part of their core curriculum requirement. Pre- and posttests assessing medical knowledge and trainee confidence in managing neurologic disease were completed by all trainees. Overall satisfaction and effectiveness were evaluated following the course. Change in trainee knowledge and confidence before and after the course was assessed for improvement. RESULTS: Sixteen trainees completed the simulation course. Prior to completion, medical knowledge was 5.2 +/- 0.9 (of 8 possible correct answers) and following the course was 6.4 +/- 1.3 (p = 0.002). Overall confidence improved from 15.4 +/- 4.9 (of 30 possible points) to 20.7 +/- 3.3 (p = <0.0001). Confidence was significantly improved for neurologic diseases directly assessed during the course (p = <0.0001) as well as for those not directly assessed (p = 0.004). CONCLUSIONS: Simulation is an effective means of neurologic education for critical care trainees, with improvement in both medical knowledge and trainee confidence after completion of a three-scenario simulation experience. This course ensures the exposure of critical care trainees to neurologic diseases that are required curricular milestones to successfully complete the fellowship training program. PMID- 27389007 TI - Smaller gray matter volume of hippocampus/parahippocampus in elderly people with subthreshold depression: a cross-sectional study. AB - BACKGROUND: Hippocampal/parahippocampal structural changes accompany major depressive disorders in the elderly, but whether subthreshold depression (StD) at an advanced age is also accompanied by similar changes in hippocampal/parahippocampal volumes is still unknown. By using voxel-based morphometry (VBM) analysis of the gray matter, we explored whether there are structural alterations of the hippocampus/parahippocampus and the correlations between its volume and participants' self-reported depressive symptoms. METHODS: Participants were 19 community-dwelling older adults with StD assessed by the Center for Epidemiologic Studies Depression scale (CES-D) scores. We collected magnetic resonance images of their brain compared to images of 17 healthy aged matched adults. We used VBM to analyze differences in gray matter volume (GMV) of the hippocampus/parahippocampus between the two groups. Moreover, we examined the correlation between the GMV of the hippocampus/parahippocampus and participants' self-reported depressive symptoms. RESULTS: VBM revealed that elderly individuals with StD had substantially reduced volumes of the right parahippocampus compared to healthy controls. Furthermore, the volumes of the hippocampus/parahippocampus were significantly associated with participants' self-reported depressive symptoms in StD. CONCLUSIONS: Gray matter volume alterations in the hippocampus/parahippocampus are correlated with subthreshold depression suggesting that early structural changes in the hippocampus/parahippocampus can constitute a risk indicator of depression. PMID- 27389008 TI - BOTRYTIS-INDUCED KINASE1, a plasma membrane-localized receptor-like protein kinase, is a negative regulator of phosphate homeostasis in Arabidopsis thaliana. AB - BACKGROUND: Plants have evolved complex coordinated regulatory networks to cope with deficiency of phosphate (Pi) in their growth environment; however, the detailed molecular mechanisms that regulate Pi sensing and signaling pathways are not fully understood yet. We report here that the involvement of Arabidopsis BIK1, a plasma membrane-localized receptor-like protein kinase that plays critical role in immunity, in Pi starvation response. RESULTS: qRT-PCR analysis revealed that expression of BIK1 was induced by Pi starvation and GUS staining indicated that the BIK1 promoter activity was detected in root, stem and leaf tissues of plants grown in Pi starvation condition, demonstrating that BIK1 is responsive to Pi starvation stress. The bik1 plants accumulated higher Pi content in root and leaf tissues and exhibited altered root architecture such as shorter primary roots, longer and more root hairs and lateral roots, as compared with those in the wild type plants, when grown under Pi sufficient and deficient conditions. Increased anthocyanin content and acid phosphatase activity, reduced accumulation of reactive oxygen species and downregulated expression of Pi starvation-induced genes including PHR1, WRKY75, AT4, PHT1;2 and PHT1;4 were observed in bik1 plants grown under Pi deficient condition. Furthermore, the expression of PHO2 was downregulated while the expression of miRNA399a and miRNA399d, which target to PHO2, was upregulated in bik1 plants, compared to the wild type plants, when grown under Pi deficient condition. CONCLUSION: Our results demonstrate that BIK1 is a Pi starvation-responsive gene that functions as a negative regulator of Pi homeostasis in Arabidopsis. PMID- 27389010 TI - CD70 Expression and Its Correlation with Clinicopathological Variables in Squamous Cell Carcinoma of the Head and Neck. AB - OBJECTIVE: Over the last decade, efforts have been made to get a better understanding of the tumor microenvironment and the role of the immune system in it. New insights into the CD27/CD70 signaling pathway point towards a role in tumor immunology, making CD70 an attractive target for immunotherapy. Here, we evaluate CD70 expression in squamous cell carcinoma of the head and neck (SCCHN). METHODS: CD70 immunohistochemistry was retrospectively performed on 95 tumor samples. Tumoral CD70 expression was scored and correlated with clinicopathological variables and overall survival (OS). RESULTS: CD70 expression in tumor cells was observed in 66 samples (69%) and was strongly associated with tumor differentiation grade (p < 0.001). CD70 expression was also observed in tumor-associated fibroblasts and endothelial cells. Additionally, the density of tumor-infiltrating lymphocytes correlated with OS (p = 0.042). CONCLUSION: This study describes the tumoral expression of CD70 in SCCHN. Results highlight the role of CD70 in tumor biology and identify CD70 as a novel therapeutic target. Further research is warranted. PMID- 27389009 TI - Full and Partial Agonism of a Designed Enzyme Switch. AB - Chemical biology has long sought to build protein switches for use in molecular diagnostics, imaging, and synthetic biology. The overarching challenge for any type of engineered protein switch is the ability to respond in a selective and predictable manner that caters to the specific environments and time scales needed for the application at hand. We previously described a general method to design switchable proteins, called "chemical rescue of structure", that builds de novo allosteric control sites directly into a protein's functional domain. This approach entails first carving out a buried cavity in a protein via mutation, such that the protein's structure is disrupted and activity is lost. An exogenous ligand is subsequently added to substitute for the atoms that were removed by mutation, restoring the protein's structure and thus its activity. Here, we begin to ask what principles dictate such switches' response to different activating ligands. Using a redesigned beta-glycosidase enzyme as our model system, we find that the designed effector site is quite malleable and can accommodate both larger and smaller ligands, but that optimal rescue comes only from a ligand that perfectly replaces the deleted atoms. Guided by these principles, we then altered the shape of this cavity by using different cavity-forming mutations, and predicted different ligands that would better complement these new cavities. These findings demonstrate how the protein switch's response can be tuned via small changes to the ligand with respect to the binding cavity, and ultimately enabled us to design an improved switch. We anticipate that these insights will help enable the design of future systems that tune other aspects of protein activity, whereby, like evolved protein receptors, remolding the effector site can also adjust additional outputs such as substrate selectivity and activation of downstream signaling pathways. PMID- 27389011 TI - Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host: implications for exosome stability and biology. AB - Extracellular vesicles (EVs) mediate communication between cells and organisms across all 3 kingdoms of life. Several reports have demonstrated that EVs can transfer molecules between phylogenetically diverse species and can be used by parasites to alter the properties of the host environment. Whilst the concept of vesicle secretion and uptake is broad reaching, the molecular composition of these complexes is expected to be diverse based on the physiology and environmental niche of different organisms. Exosomes are one class of EVs originally defined based on their endocytic origin, as these derive from multivesicular bodies that then fuse with the plasma membrane releasing them into the extracellular environment. The term exosome has also been used to describe any small EVs recovered by high-speed ultracentrifugation, irrespective of origin since this is not always well characterized. Here, we use comparative global lipidomic analysis to examine the composition of EVs, which we term exosomes, that are secreted by the gastrointestinal nematode, Heligmosomoides polygyrus, in relation to exosomes secreted by cells of its murine host. Ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) analysis reveals a 9- to 62-fold enrichment of plasmalogens, as well as other classes of ether glycerophospholipids, along with a relative lack of cholesterol and sphingomyelin (SM) in the nematode exosomes compared with those secreted by murine cells. Biophysical analyses of the membrane dynamics of these exosomes demonstrate increased rigidity in those from the nematode, and parallel studies with synthetic vesicles support a role of plasmalogens in stabilizing the membrane structure. These results suggest that nematodes can maintain exosome membrane structure and integrity through increased plasmalogens, compensating for diminished levels of other lipids, including cholesterol and SM. This work also illuminates the prevalence of plasmalogens in some EVs, which has not been widely reported and could have implications for the biochemical or immunomodulatory properties of EVs. Further comparative analyses such as those described here will shed light on diversity in the molecular properties of EVs that enable them to function in cross-species communication. PMID- 27389012 TI - Platelet-rich plasma stimulates human dermal fibroblast proliferation via a Ras dependent extracellular signal-regulated kinase 1/2 pathway. AB - Platelet-rich plasma (PRP) contains a high concentration of several growth factors and contributes to soft-tissue engineering and wound healing. However, the effect of PRP on human dermal fibroblast proliferation and responses is unknown. This was investigated in the present study using PRP prepared from the whole human blood using the double-spin method. Human dermal fibroblast cultures were established from skin samples collected during plastic surgery. Platelet concentration and growth factor levels in PRP were estimated, and a cell proliferation assay was carried out after PRP treatment. The role of Ras dependent extracellular signal-regulated kinase (ERK)1/2 in the effects of PRP was investigated in human dermal fibroblasts by suppressing ERK1/2 expression with an inhibitor or by short interfering (si)RNA-mediated knockdown, and assessing ERK1/2 phosphorylation by western blotting as well as proliferation in PRP-treated cells. We found that PRP stimulated human dermal fibroblast proliferation, which was suppressed by ERK1/2 inhibitor treatment (P < 0.01). ERK1/2 phosphorylation was increased in the presence of PRP, while siRNA-mediated knockdown of ERK1/2 blocked cell proliferation normally induced by PRP treatment (P < 0.01). These results demonstrate that PRP induces human dermal fibroblast proliferation via activation of ERK1/2 signaling. Our findings provide a basis for the development of agents that can promote wound healing and can be applied to soft-tissue engineering. PMID- 27389013 TI - Eribulin-induced liver dysfunction as a prognostic indicator of survival of metastatic breast cancer patients: a retrospective study. AB - BACKGROUND: Eribulin is a non-taxane, microtubule dynamics inhibitor that increases survival of patients with metastatic breast cancer. Although eribulin is well tolerated in patients with heavily pretreated disease, eribulin-induced liver dysfunction (EILD) can occur, resulting in treatment modification and subsequent poor disease control. We aimed to clarify the effect of EILD on patient survival. METHODS: The medical records of 157 metastatic breast cancer patients treated with eribulin between July 2011 and November 2013 at Cancer Institute Hospital were retrospectively analyzed. EILD was defined as 1) an increase in alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal, and/or 2) initiation of a liver-supporting oral drug therapy such as ursodeoxycholic acid or glycyron. Fatty liver was defined as a decrease in the liver-to-spleen attenuation ratio to <0.9 on a computed tomography scan. RESULTS: EILD occurred in 42 patients, including one patient for whom eribulin treatment was discontinued due to severe EILD. The patients who developed EILD had significantly higher body mass indices (BMIs) than those who did not develop EILD (24.5 vs. 21.5, respectively; P < 0.0001), with no difference in the dose intensity of eribulin between the two groups (P = 0.76). Interestingly, the patients with EILD exhibited significantly longer progression free survival (PFS) and overall survival (OS) than those without EILD (P = 0.010 and P = 0.032, respectively). Similarly, among 80 patients without liver metastasis, 19 with EILD exhibited significantly longer PFS and OS than the others (P = 0.0012 and P = 0.044, respectively), and EILD was an independent prognostic factor of PFS (P = 0.0079) in multivariate analysis. During eribulin treatment, 18 patients developed fatty liver, 11 of whom developed EILD, with a median BMI of 26.7. CONCLUSIONS: Although EILD and fatty liver occurred at a relatively high frequency in our study, most of the patients did not experience severe adverse effects. Surprisingly, the development of EILD was positively associated with patient survival, especially in patients without liver metastases. EILD may be a clinically useful predictive biomarker of survival, but further studies are needed to confirm these findings in another cohort of patients. PMID- 27389014 TI - [Statin and cardiovascular diseases after 75 years]. AB - Statin prescription in persons older than 75 years or with frailty signs raises questions on the role of cholesterol in the genesis of atherosclerosis in this population, on the benefit of this treatment in primary or secondary prevention, and on their side effects in a context of multiple pathology and multiple medications. These questions are approached with the available literature data for this population. In secondary prevention, statin prescription is recommended whatever the age although intensive treatment should be avoided. In primary prevention, in the absence of consensus, their prescription depends on both geriatric and cardiovascular risk assessment. PMID- 27389015 TI - Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients. AB - BACKGROUND: The soluble CD14 subtype, Presepsin, appears to be an accurate sepsis diagnostic marker, but data from intensive care units (ICUs) are scarce. This study was conducted to evaluate the diagnostic and prognostic value of Presepsin in ICU patients with severe sepsis (SS), septic shock (SSh) and severe community acquired pneumonia (sCAP). METHODS: Presepsin and procalcitonin (PCT) levels were determined for patients at admission to ICU. Four groups have been differentiated: (1) absence or (2) presence of systemic inflammatory response syndrome, (3) SS or (4) SSh; and 2 groups, among the patients admitted for acute respiratory failure: absence or presence of sCAP. Biomarkers were tested for diagnosis of SS, SSh and sCAP and for prediction of ICU mortality. RESULTS: One hundred and forty-four patients were included: 44 SS and 56 SSh. Plasma levels of Presepsin and PCT were significantly higher in septic than in non-septic patients and in SSh as compared to others. The sepsis diagnostic accuracy of Presepsin was not superior to that of PCT (AUC: 0.75 vs 0.80). In the 72/144 patients admitted for acute respiratory failure, the capability of Presepsin to diagnose sCAP was significantly better than PCT. Presepsin levels were also predictive of ICU mortality in sepsis and in sCAP patients. CONCLUSION: Plasma levels of Presepsin were useful for the diagnosis of SS, SSh and sCAP and may predict ICU mortality in these patients. PMID- 27389016 TI - Effect of simulated patient death on emergency worker's anxiety: a cluster randomized trial. AB - OBJECTIVE: Simulation-based teaching offers promising and diverse teaching possibilities. We aim to assess whether the death of the manikin increased anxiety amongst learner compared to similar simulation-based course where the manikin stays alive. METHODS: We conducted a cluster randomized study amongst multidisciplinary teams of emergency workers. Teams of physicians, nurses, and healthcare assistants were randomly assigned to participate in a simulation-based course where the simulated patient died (death group) or not (life group). We assessed anxiety at 1 month after the teaching using Spielberger STAI-state anxiety questionnaire. We compared reduction of anxiety when facing a life threatening situation in both groups. RESULTS: We included 25 teams for a total of 129 participants. We analysed 63 participants in the death group and 57 in the life group. Baseline characteristics were similar in both groups, including baseline anxiety (STAI-state score 39.6 (7.8) in the death group vs 38.6 (7.1) in the life group). We report a significant reduction in both groups 1 month after the training: 6.6 (7.8) vs 6 (8.0), mean difference 0.5 (-2.4; 3.4). At 3 months, we report a significant greater reduction of anxiety in the death group (mean difference 4 [0.1; 7.9]). CONCLUSION: We observed in our sample that unexpected simulated patient death did not increase anxiety amongst multidisciplinary emergency workers. PMID- 27389017 TI - Atypical Asymmetry for Processing Human and Robot Faces in Autism Revealed by fNIRS. AB - Deficits in the visual processing of faces in autism spectrum disorder (ASD) individuals may be due to atypical brain organization and function. Studies assessing asymmetric brain function in ASD individuals have suggested that facial processing, which is known to be lateralized in neurotypical (NT) individuals, may be less lateralized in ASD. Here we used functional near-infrared spectroscopy (fNIRS) to first test this theory by comparing patterns of lateralized brain activity in homologous temporal-occipital facial processing regions during observation of faces in an ASD group and an NT group. As expected, the ASD participants showed reduced right hemisphere asymmetry for human faces, compared to the NT participants. Based on recent behavioral reports suggesting that robots can facilitate increased verbal interaction over human counterparts in ASD, we also measured responses to faces of robots to determine if these patterns of activation were lateralized in each group. In this exploratory test, both groups showed similar asymmetry patterns for the robot faces. Our findings confirm existing literature suggesting reduced asymmetry for human faces in ASD and provide a preliminary foundation for future testing of how the use of categorically different social stimuli in the clinical setting may be beneficial in this population. PMID- 27389018 TI - Near-IR transillumination and reflectance imaging at 1,300 nm and 1,500-1,700 nm for in vivo caries detection. AB - INTRODUCTION: Several studies suggest that near-IR imaging methods at wavelengths longer than 1,300 nm have great potential for caries detection. In this study, the diagnostic performance of both near-IR transillumination and near-IR reflectance was assessed on teeth scheduled for extraction due to orthodontic treatment (n = 109 teeth on 40 test subjects). METHODS: Three intra-oral near-IR imaging probes were fabricated for the acquisition of in vivo images using a high definition InGaAs camera and near-IR broadband light sources. Two transillumination probes provided occlusal and approximal images using 1,300 nm light which manifests the highest transparency in enamel. A third reflectance probe utilized cross-polarization and operated at wavelengths greater than 1,500 nm where water absorption is higher which reduces the reflectivity of sound tissues, significantly increasing lesion contrast. Teeth were collected after extraction and sectioned and examined with polarized light microscopy and microradiography which served as the gold standard. In addition, radiographs were taken of the teeth and the diagnostic performance of near-IR imaging was compared with radiography. RESULTS: Near-IR imaging was significantly more sensitive (P < 0.05) than radiography for the detection of lesions on both occlusal and proximal surfaces. CONCLUSION: Near-IR imaging methods are ideally suited for screening all tooth surfaces for carious lesions. Lasers Surg. Med. 48:828-836, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27389019 TI - Efficacy of the Essential Amino Acids and Keto-Analogues on the CKD progression rate in real practice in Russia - city nephrology registry data for outpatient clinic. AB - BACKGROUND: Renal replacement therapy (RRT) is growing by 10 % per year in Russia, but pre-dialysis care which can retard CKD progression and delay the start of RRT remains limited. We evaluate the effect of Essential Amino Acids and Keto-analogues (EAA/KA) on CKD progression. METHODS: The effect of low protein diet (LPD), supplemented by EAA/KA, on GFR slope changes between first and second treatment period (five sequential visits per period) in 96 patients withs CKD Stage 3B-5 was compared to GFR slope changes in the control group of 96 patients, randomly selected from matched (by gender, age, diagnosis and CKD Stage) cohort of 320 patients from the city Registry. The mean baseline eGFR was 23 +/- 9 ml/min/1.73 m2; 29 % had CKD3B, 45 % - CKD4, 26 % - CKD5. RESULTS: The rate of eGFR decline changed from -2.71 +/- 2.38 to -2.01 +/- 2.26 ml/min/1.73 m2 per year in the treatment group and from -2.18 +/- 2.01 to -2.04 +/- 2.18 ml/min/1.73 m2 per year in the control group. Only in the treatment group the difference was significant (p = 0.04 and p = 0.6). Standardized effect size for intervention was significant in treatment group: -0.3 (of pooled SD), 95 % CI -0.58 / -0.02 and non-significant in control group: -0.07 (-0.35 / +0.22). The univariate and multivariate analysis of EAA/KA therapy effect demonstrated that it was probably more effective in patients of older age, with higher time-averaged proteinuria (PU), lower phosphate level, in patients with glomerular v. interstitial diseases, and in females. Only the latter factor was significant at pre-specified level (<0.05). CONCLUSIONS: LPD combined with EAA/KA supplementation lead to the decrease of the CKD progression both in well-designed clinical study and in real nephrology practice in wide variety diseases and settings. Registry data can be helpful to reveal patients with optimal chances for beneficial effect of LPD supplemented by EAA/KA. TRIAL REGISTRATION: ISRCTN28190556 06/05/2016. PMID- 27389021 TI - High-quality Linac-based Stereotactic Body Radiation Therapy with Flattening Filter Free Beams and Volumetric Modulated Arc Therapy for Low-Intermediate Risk Prostate Cancer. A Mono-institutional Experience with 90 Patients. AB - AIMS: The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer. MATERIALS AND METHODS: Biopsy-confirmed prostate cancer patients were enrolled, provided that they had the following characteristics: initial prostate specific antigen (PSA) <= 20 ng/ml, Gleason Score < 7, International Prostate Symptom Score < 7. The treatment schedule was 35 Gy in five fractions, delivered with volumetric modulated arcs with flattening filter free beams. Toxicity was recorded according to CTCAE criteria v4.0. Biochemical failure was calculated according to the Phoenix definition. The Expanded Prostate Cancer Index Composite questionnaire was used to record health-related quality of life. RESULTS: Between December 2011 and March 2015, 90 patients were enrolled (53 low risk, 37 intermediate risk). The median age was 71 years (range 48-82). In total, 58 (64.5%) of the patients had Gleason Score=6, the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml (range 2.7-17.0). Acute toxicity was mild, with 32.2 patients presenting grade 1 urinary toxicity and 32.2% of patients presenting grade 2 urinary toxicity, mainly represented by urgency, dysuria and stranguria. Rectal grade 1 toxicity was found in 15.5% of patients, whereas grade 2 toxicity was recorded in 6.6% of patients. Regarding late toxicity, grade 1 proctitis was recorded in 11.1% of patients and grade 1 urinary in 38.8%; only two events of grade 2 urinary toxicity were observed (transient urethral stenosis, resolved by a 24 h catheterisation). At a median follow-up of 27 months (6-62 months) only two intermediate risk patients experienced a biochemical failure. Health-related quality of life revealed a slight worsening in all the domains during treatment, with a return to baseline 3 months after treatment. CONCLUSIONS: Stereotactic body radiotherapy delivered using linac based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life. PMID- 27389020 TI - Profile of Risk Factors for Non-Communicable Diseases in Punjab, Northern India: Results of a State-Wide STEPS Survey. AB - BACKGROUND: Efforts to assess the burden of non-communicable diseases risk factors has improved in low and middle-income countries after political declaration of UN High Level Meeting on NCDs. However, lack of reliable estimates of risk factors distribution are leading to delay in implementation of evidence based interventions in states of India. METHODS: A STEPS Survey, comprising all the three steps for assessment of risk factors of NCDs, was conducted in Punjab state during 2014-15. A statewide multistage sample of 5,127 residents, aged 18 69 years, was taken. STEPS questionnaire version 3.1 was used to collect information on behavioral risk factors, followed by physical measurements and blood and urine sampling for biochemical profile. RESULTS: Tobacco and alcohol consumption were observed in 11.3% (20% men and 0.9% women) and 15% (27% men and 0.3% women) of the population, respectively. Low levels of physical activity were recorded among 31% (95% CI: 26.7-35.5) of the participants. The prevalence of overweight and obesity was 28.6% (95% CI: 26.3-30.9) and 12.8% (95% CI: 11.2 14.4) respectively. Central obesity was higher among women (69.3%, 95% CI: 66.5 72.0) than men (49.5%, 95% CI: 45.3-53.7). Prevalence of hypertension in population was 40.1% (95% CI: 37.3-43.0). The mean sodium intake in grams per day for the population was 7.4 gms (95% CI: 7.2-7.7). The prevalence of diabetes (hyperglycemia), hypertriglyceridemia and hypercholesterolemia was 14.3% (95% CI: 11.7-16.8), 21.6% (95% CI: 18.5-25.1) and 16.1% (95% CI: 13.1-19.2), respectively. In addition, 7% of the population aged 40-69 years had a cardiovascular risk of >= 30% over a period of next 10 years. CONCLUSION: We report high prevalence of risk factors of chronic non-communicable diseases among adults in Punjab. There is an urgent need to implement population, individual and programme wide prevention and control interventions to lower the serious consequences of NCDs. PMID- 27389022 TI - A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models. AB - Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons. PMID- 27389023 TI - In silico search, characterization and validation of new EST-SSR markers in the genus Prunus. AB - BACKGROUND: Simple sequence repeats (SSRs) are defined as sequence repeat units between 1 and 6 bp that occur in both coding and non-coding regions abundant in eukaryotic genomes, which may affect the expression of genes. In this study, expressed sequence tags (ESTs) of eight Prunus species were analyzed for in silico mining of EST-SSRs, protein annotation, and open reading frames (ORFs), and the identification of codon repetitions. RESULTS: A total of 316 SSRs were identified using MISA software. Dinucleotide SSR motifs (26.31 %) were found to be the most abundant type of repeats, followed by tri- (14.58 %), tetra- (0.53 %), and penta- (0.27 %) nucleotide motifs. An attempt was made to design primer pairs for 316 identified SSRs but these were successful for only 175 SSR sequences. The positions of SSRs with respect to ORFs were detected, and annotation of sequences containing SSRs was performed to assign function to each sequence. SSRs were also characterized (in terms of position in the reference genome and associated gene) using the two available Prunus reference genomes (mei and peach). Finally, 38 SSR markers were validated across peach, almond, plum, and apricot genotypes. This validation showed a higher transferability level of EST-SSR developed in P. mume (mei) in comparison with the rest of species analyzed. CONCLUSIONS: Findings will aid analysis of functionally important molecular markers and facilitate the analysis of genetic diversity. PMID- 27389024 TI - Use of complementary and alternative medicine in pregnancy: a cross-sectional survey on Iraqi women. AB - BACKGROUND: Due to the lack of strong evidence on safety and efficacy of complementary and alternative medicine (CAM) approaches, the use of CAM in women during pregnancy could be hazardous for mother and fetus. Meanwhile, little is known regarding the patterns, the reasons and the factors affecting use of CAM among pregnant women in Iraq. METHODS: A cross sectional survey design was used to carry out face-to-face interviews with 335 consecutive pregnant women. The questionnaire comprised of three sections: socio-demographic characteristics, pregnancy-related aspects and the patterns and attitudes towards use of CAM. Determinants of CAM use were assessed through the logistic regression analysis. RESULTS: Three hundred thirty-five pregnant women completed the questionnaire. 56.7 % reported using at least one form of CAM modalities. In total, 24 different types of CAM were used; with herbal medicine (53.7 %) and multivitamins (36.3 %) the most commonly used modalities. From the logistic regression analysis, the variables positively associated with CAM use were: rural residence (odds ratio (OR) 2.0, p < 0.01), no occupation (OR 2.7, p < 0.05), high income (OR 2.0, p < 0.05), perceived healthy status (OR 2.6, p < 0.05) and ever use of contraception (OR 2.0, p < 0.01). Only 0.5 % of CAM users disclosed their CAM use to physicians. CONCLUSIONS: The proportion of CAM users among pregnant women is relatively high and it is important to learn what types of CAM they use. However, disclosure of CAM use was extraordinarily low. Given the low rate of disclosure, it should be ensured that physicians establish good level of communication with pregnant women and have adequate knowledge of CAM. PMID- 27389025 TI - Using noninvasive ventilation to prevent extubation failure: it is good news, but do we really know what "high risk" means? PMID- 27389026 TI - From Slow Viruses to Prions. PMID- 27389027 TI - A Total Synthesis of Paeoveitol. AB - A four-step total synthesis of paeoveitol (1), a recently disclosed norditerpene natural product from Paeonia vetchii, is reported. This highly concise synthetic route was guided by biosynthetic considerations and enabled by an unusual intermolecular ortho-quinone methide [4 + 2]-cycloaddition reaction, which proceeded with excellent regio- and diastereoselectivity. Density functional theory (DFT) calculations point to a crucial intermolecular hydrogen bond and pi pi stacking interaction that govern selectivity in this process. PMID- 27389028 TI - Simulation of human plasma concentration-time profiles of the partial glucokinase activator PF-04937319 and its disproportionate N-demethylated metabolite using humanized chimeric mice and semi-physiological pharmacokinetic modeling. AB - 1. The partial glucokinase activator N,N-dimethyl-5-((2-methyl-6-((5 methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF 04937319) is biotransformed in humans to N-methyl-5-((2-methyl-6-((5 methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (M1), accounting for ~65% of total exposure at steady state. 2. As the disproportionately abundant nature of M1 could not be reliably predicted from in vitro metabolism studies, we evaluated a chimeric mouse model with humanized liver on TK-NOG background for its ability to retrospectively predict human disposition of PF-04937319. Since livers of chimeric mice were enlarged by hyperplasia and contained remnant mouse hepatocytes, hepatic intrinsic clearances normalized for liver weight, metabolite formation and liver to plasma concentration ratios were plotted against the replacement index by human hepatocytes and extrapolated to those in the virtual chimeric mouse with 100% humanized liver. 3. Semi-physiological pharmacokinetic analyses using the above parameters revealed that simulated concentration curves of PF-04937319 and M1 were approximately superimposed with the observed clinical data in humans. 4. Finally, qualitative profiling of circulating metabolites in humanized chimeric mice dosed with PF-04937319 or M1 also revealed the presence of a carbinolamide metabolite, identified in the clinical study as a human-specific metabolite. The case study demonstrates that humanized chimeric mice may be potentially useful in preclinical discovery towards studying disproportionate or human-specific metabolism of drug candidates. PMID- 27389030 TI - Specific MAPK inhibitors prevent hyperglycemia-induced renal diseases in type 1 diabetic mouse model. AB - Mitogen-activated protein kinase (MAPK) and renin-angiotensin system (RAS) play critical roles in the process of renal diseases, but their interaction has not been comprehensively discussed. In the present studies, we investigated the renoprotective effects of MPAK inhibitors on renal diseases in type 1 diabetic mouse model, and clarify the crosstalk among MAPK signaling. Type 1 diabetic mouse model was established in male C57BL/6 J mice, and treated with or without 10 mg/kg MAPK blockers, including ERK inhibitor PD98059, p38 inhibitor SB203850, and JNK inhibitor SP600125 for four weeks. Hyperglycemia induced renal injuries, but treating them with MAPK inhibitors significantly decreased glomerular volume and glycogen in renal tissues. Although slightly changed body weight and fasting blood glucose levels, MAPK inhibitors attenuated blood urea nitrogen, urea protein, and microalbuminuria. Administration also reduced the diabetes-induced RAS activation, including angiotensin II converting enzyme (c) and Ang II, which contributed to its renal protective effects in the diabetic mice. In addition, the anti-RAS of MAPK inhibitor treatment markedly reduced gene expression of tumor necrosis factor-alpha, interleukin-6, and inducible nitric oxide synthase, fibrotic accumulation, and transforming growth factor-beta1 levels in renal tissues. Furthermore, chemical inhibitors and genetic siRNA results identified the crosstalk among the three MAPK signaling, and proved JNK signaling played a critical role in MAPK-mediated ACE pathway in hyperglycemia state. Collectively, these results support the therapeutic effects of MAPK-specific inhibitors, especially JNK inactivation, on hyperglycemia-induced renal damages. PMID- 27389029 TI - **-Postprandial pancreatic [11C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release. AB - PURPOSE: [S-methyl-11C]-L-methionine ([11C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [11C]MET uptake. METHODS: Nineteen tumor-free survivors after PD (age mean +/- SD: 61 +/- 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 +/- 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [11C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. RESULTS: The uptake of [11C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC30 correlated with the SUVmax increment between 15 and 30 minutes (R2 = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [11C]MET. Total integrated SUVmax correlated with insulin AUC60 (R2 = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of 11C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R2 = 0.78, p < 0.0001). CONCLUSION: Postprandial [11C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function. PMID- 27389031 TI - Vestibulo-Oral inclination of maxillary and mandibular canines and bicuspids - a CBCT investigation. AB - BACKGROUND: The aim of this retrospective study was to measure tooth and crowns axes of canines, first and second bicuspids of orthodontically untreated subjects with near normal occlusion to: 1. Define norms and reveal potential gender differences and 2. Discuss implications of the findings for orthodontics. METHODS: The CBCT-datasets of 167 patients, 56 males (mean age 28.63 years +/- 11.99 years) and 111 females (mean age 29.72 years +/- 11.47 years) were used. Tooth- and crown axes were measured for right and left sides. Normal distribution was evaluated with the Kolmogorov-Smirnov-test. For gender comparison independent t-Tests and for comparison of right and left sides a paired t-Test were used for normally distributed data. For data not following normal distribution for gender comparison the Mann-Whitney-U-Test was used and for data comparing the two sides the Wilcoxon signed rank test was applied. The level of statistical significance was set at p <= 0.05. RESULTS: Measurement of tooth axes revealed buccal inclination for both genders with maximum values for maxillary and mandibular canines. Statistical significant differences were only found for maxillary canines (P = 0.025) and lower second bicuspids (P = 0.016) respectively. Values for crown axes revealed oral inclination for both genders with maximum values for maxillary first bicuspids and in the mandible for first and second bicuspids. No statistical significant differences were found between the genders apart from asymmetry for crown axes for the upper first bicuspids for males (P = 0.006) and females (P < 0.001). CONCLUSIONS: Our study reveals that irrespective of gender, oral inclination of the crowns of canines and premolars is the norm. The values of the most commonly used bracket prescriptions coincide with the average values found in our investigation. For esthetic reasons modifications of torque values can be considered. PMID- 27389032 TI - Eating behaviour associated with differences in conflict adaptation for food pictures. AB - OBJECTIVE: The goal conflict model of eating (Stroebe, Mensink, Aarts, Schut, & Kruglanski, 2008) proposes differences in eating behaviour result from peoples' experience of holding conflicting goals of eating enjoyment and weight maintenance. However, little is understood about the relationship between eating behaviour and the cognitive processes involved in conflict. This study aims to investigate associations between eating behaviour traits and cognitive conflict processes, specifically the application of cognitive control when processing distracting food pictures. METHOD: A flanker task using food and non-food pictures was used to examine individual differences in conflict adaptation. Participants responded to target pictures whilst ignoring distracting flanking pictures. Individual differences in eating behaviour traits, attention towards target pictures, and ability to apply cognitive control through adaptation to conflicting picture trials were analysed. RESULTS: Increased levels of external and emotional eating were related to slower responses to food pictures indicating food target avoidance. All participants showed greater distraction by food compared to non-food pictures. Of particular significance, increased levels of emotional eating were associated with greater conflict adaptation for conflicting food pictures only. CONCLUSION: Emotional eaters demonstrate greater application of cognitive control for conflicting food pictures as part of a food avoidance strategy. This could represent an attempt to inhibit their eating enjoyment goal in order for their weight maintenance goal to dominate. PMID- 27389033 TI - Adolescent energy drink consumption: An Australian perspective. AB - Caffeinated Energy Drinks (EDs) are not recommended for consumption by children, yet there is a lack of age-specific recommendations and restrictions on the marketing and sale of EDs. EDs are increasingly popular among adolescents despite growing evidence of their negative health effects. In the current study we examined ED consumption patterns among 399 Australian adolescents aged 12-18 years. Participants completed a self-report survey of consumption patterns, physiological symptoms, and awareness of current ED consumption guidelines. Results indicated that ED consumption was common among the sample; 56% reported lifetime ED consumption, with initial consumption at mean age 10 (SD = 2.97). Twenty-eight percent of the sample consumed EDs at least monthly, 36% had exceeded the recommended two standard EDs/day, and 56% of consumers had experienced negative physiological health effects following ED consumption. The maximum number of EDs/day considered appropriate for children, adolescents, and adults varied, indicating a lack of awareness of current consumption recommendations. These findings add to the growing body of international evidence of adolescent ED consumption, and the detrimental impact of EDs to adolescent health. Enforced regulation and restriction of EDs for children's and adolescents' consumption is urgently needed in addition to greater visibility of ED consumption recommendations. PMID- 27389035 TI - Does Thermal Breathing Affect Collision Cross Sections of Gas-Phase Peptide Ions? An Ab Initio Molecular Dynamics Study. AB - Ab initio molecular dynamics (AIMD) with density functional theory (DFT) was applied to explore conformational motions and collision cross sections (Omega) of folded (2) and extended (7) conformers of doubly charged peptide ions, (Ala-Ala Leu-Arg + 2H)(2+), in the gas phase at 300 and 473 K. The experimental Omega of (Ala-Ala-Leu-Arg +2H)(2+) was measured as 149 +/- 1.2 A(2) at 298 K. Thermally distributed mean values of Omega for 2 and 7 at 300 and 473 K were only 0.8-1.1% larger than for the equilibrium 0 K structures. Long (>10 ps) trajectory calculations indicated entropy-driven conformational change of 2 to 7 that occurred at random within a ~ 4 ps time window. The experimental Omega was found to fit the calculated population averaged values for 2 and 7, indicating a rapid conformer interconversion. Overall, thermal breathing had only a minor effect on the peptide ion collision cross sections. PMID- 27389034 TI - Relationships between psychosocial outcomes in adolescents who are obese and their parents during a multi-disciplinary family-based healthy lifestyle intervention: One-year follow-up of a waitlist controlled trial (Curtin University's Activity, Food and Attitudes Program). AB - BACKGROUND: Limited studies have investigated relationships in psychosocial outcomes between adolescents who are obese and their parents and how psychosocial outcomes change during participation in a physical activity and healthy eating intervention. This study examined both adolescent and parent psychosocial outcomes while participating in a one - year multi-disciplinary family-based intervention: Curtin University's Activity, Food, and Attitudes Program (CAFAP). METHODS: Following a waitlist control period, the intervention was delivered to adolescent (n = 56, ages 11-16) and parent participants over 8 weeks, with one year maintenance follow-up. Adolescent depression and quality of life, family functioning, and parent depression, anxiety, and stress were assessed at six time points: baseline and prior to intervention (e.g., waitlist control period), immediately following intervention, and at 3, 6, and 12 months post-intervention. Relationships between adolescent and parent psychosocial outcomes were assessed using Spearman correlations and changes in both adolescent and parent outcomes were assessed using linear mixed models. Changes in adolescent psychosocial outcomes were compared to changes in behavioural (physical activity and healthy eating) and physical (weight) outcomes using independent samples t-tests. RESULTS: The majority of psychosocial outcomes were significantly correlated between adolescents and parents across the one-year follow-up. Adolescent depression, psychosocial and physical quality of life outcomes significantly improved before or following intervention and were maintained at 6-months or one year follow-up. Parent symptoms of depression, anxiety, and stress were reduced during waitlist and primarily remained improved. Changes in adolescent psychosocial outcomes were shown to be partially associated with behavioural changes and independent of physical changes. CONCLUSIONS: Adolescents in CAFAP improved psychosocial and physical quality of life and reversed the typical trajectory of depressive symptoms in adolescents who are obese during a one-year maintenance period. CAFAP was also effective at maintaining reductions in parent symptoms of depression, anxiety, and stress demonstrated during the waitlist period. TRIAL REGISTRATION: The trial was registered with the Australian and New Zealand Clinical Trials Registry (No. 12611001187932 ). PMID- 27389037 TI - Investigation of the cytotoxic implications of metal chelators against melanoma and approaches to improve the cytotoxicity profiles of metal coordinating agents. AB - The cytotoxic activity of thiosemicarbazones (TSC) and thiocarbohydrazones was investigated against the MelRm melanoma cell line. In general, the melanoma line was susceptible to metal coordinating agents, the most useful of which incorporated the dipyridyl ketone hydrazone sub-structure. The impact of copper supplementation on the cytotoxic activity towards the melanoma line (MelRm) of metal coordinating agents when acting as ionophores is less predictable than the general improvement that has been seen in other cancer cells such as breast adenocarcinoma (MCF-7). The bimetallic nature of thiocarbohydrazone complexes with resultant loss of lipophilicity is a limiting factor in usage against MelRm. The cytotoxic activity of TSC against MelRm when used as copper ionophores could be markedly improved through combination with a partner drug capable of disrupting cellular defences to oxidative stress. In the absence of copper supplementation, both TSC and thiocarbohydrazones could be used to initiate cell cycle arrest and this could be employed to improve cytotoxicity profiles of other metallodrugs such as cisplatin. PMID- 27389036 TI - Does mean heart dose sufficiently reflect coronary artery exposure in left-sided breast cancer radiotherapy? : Influence of respiratory gating. AB - PURPOSE: With extensive use of systemic treatment, the issue of cardiac mortality after breast cancer radiation (RT) is still important. The aim of our analysis was to clarify whether the dose to one surrogate parameter (e. g., mean heart dose, as used in most studies) reflects the dose to the other cardiovascular structures especially the left anterior descending artery depending on breathing adapted RT. PATIENTS AND METHODS: A total of 130 patients who underwent adjuvant RT (50.4 Gy plus boost 9-16 Gy) were evaluated. In all, 71 patients were treated with free-breathing and 59 patients using respiratory monitoring (gated RT). Dosimetric associations were calculated. RESULTS: The mean dose to the heart (Dmean heart) was reduced from 2.7 (0.8-5.2) Gy to 2.4 (1.1-4.6) Gy, the Dmean LAD (left anterior descending artery) decreased from 11.1 (1.3-28.6) Gy to 9.3 (2.2-19.9) Gy with gated RT (p = 0.04). A significant relationship was shown for Dmean heart-Dmean LAD, V25heart-Dmean LAD and Dmax heart-Dmax LAD for gated patients only (p < 0.01). For every 1 Gy increase in Dmean heart, mean LAD doses rose by 3.6 Gy, without gating V25 <=5 % did not assure a benefit and resulted in Dmean LAD between 1.3 and 28.6 Gy. CONCLUSION: A significant reduction and association of heart and coronary artery (LAD) doses using inspiratory gating was shown. However, in free-breathing plans commonly measured dose constraints do not allow precise estimation of the dose to the coronary arteries. PMID- 27389038 TI - Revised global consensus statement on menopausal hormone therapy. AB - The following Consensus Statement is endorsed by The International Menopause Society, The North American Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The Asia Pacific Menopause Federation, The International Osteoporosis Foundation and The Federation of Latin American Menopause Societies. PMID- 27389039 TI - Quantum Chemical Study of the Low-Lying Electronic States of VSi3(-/0) Clusters and Interpretation of the Anion Photoelectron Spectrum. AB - The geometrical and electronic structures of VSi3(-/0) clusters have been investigated with the DFT, CCSD(T), and CASSCF/CASPT2 methods. The results showed that the suitable functional to identify the ground states of VSi3(-/0) clusters is not the B3LYP but the BP86. At the BP86, CCSD(T), and CASPT2 levels, the ground state of the anionic cluster was the (1)A' ((1)A1) of tetrahedral eta(3) (Si3)V(-) isomer, while that of the neutral cluster was the 1(2)A' and 1(2)A" (1(2)E) of the same isomer. The 1(2)A' and 1(2)A" of the tetrahedral eta(3) (Si3)V isomer were the results of the Jahn-Teller distortions of the 1(2)E in C3v symmetry. All three bands in the photoelectron spectrum of the VSi3(-) cluster were interpreted by one-electron detachments from the (1)A' anionic ground state on the basis of the BP86, CCSD(T), and CASPT2 methods. The calculated adiabatic and vertical detachment energies were in agreement with the experimental values. The broad shape of the first band was explained by Franck-Condon factor simulations for the (1)A' -> 1(2)A' and (1)A' -> 1(2)A" transitions within the tetrahedral eta(3)-(Si3)V(-/0) isomers. PMID- 27389041 TI - Providing Universal Health Insurance Coverage in Nigeria. AB - Despite a stated goal of achieving universal coverage, the National Health Insurance Scheme of Nigeria had achieved only 4% coverage 12 years after it was launched. This study assessed the plans of the National Health Insurance Scheme to achieve universal health insurance coverage in Nigeria by 2015 and discusses the challenges facing the scheme in achieving insurance coverage. In-depth interviews from various levels of the health-care system in the country, including providers, were conducted. The results of the analysis suggest that challenges to extending coverage include the difficulty in convincing autonomous state governments to buy into the scheme and an inadequate health workforce that might not be able to meet increased demand. Recommendations for increasing the scheme's coverage include increasing decentralization and strengthening human resources for health in the service delivery systems. Strong political will is needed as a catalyst to achieving these goals. PMID- 27389042 TI - The Challenges of Laryngeal Preservation-Is It the Systemic Agent or the Proper Sequence of Therapy? PMID- 27389040 TI - INFalpha-2b inhibitory effects on CD4(+)CD25(+)FOXP3(+) regulatory T cells in the tumor microenvironment of C57BL/6 J mice with melanoma xenografts. AB - BACKGROUND: Regulatory T cells (Tregs), particularly the CD4(+)CD25(+)Foxp3(+) Tregs, down regulate immunity and promote tumor cell growth by directly suppressing CD8(+) and CD4(+) T cells. Alternatively they can promote tumor growth by generating interleukin-10 (IL-10) and transforming growth factor beta (TGFbeta) in situ, which help tumor cells to evade the immune system. METHODS: In vivo tumor models were prepared via subcutaneous injection with a suspension of B16 melanoma cells into the left upper flank of C57BL/6 J mice. The mice were randomized into five groups: radiotherapy (RT), chemotherapy (CT), radiochemotherapy (RCT), Inteferon alpha (INFalpha) groups, and a control group. Flow cytometry was used to determine the Tregs levels in the spleen and peripheral blood, and immunohistochemistry was performed to determine the expression levels of TGFbeta and IL-10 in the tumor microenvironment. RESULTS: Tumor weight was significantly reduced in the CT or RCT groups (40.91 % and 41.83 %, respectively), while the reduction in tumor weight was relatively lower for the RT and IFNalpha groups (15.10 % and 13.15 %, respectively). The flow cytometry results showed that the ratios of CD4(+)CD25(+)Foxp3(+) Tregs to lymphocytes and CD4(+) cells in the spleen and in peripheral blood were significantly decreased after treatment with IFNalpha (P < 0.05). Expression of TGFbeta and IL-10 in the tumor microenvironment in the CT and RT groups was higher compared with the control group (P < 0.01), while the expression of TGFbeta and IL-10 in the INFalpha group was not significantly different (P > 0.05). CONCLUSIONS: The results show that INFalpha-2b inhibits cancer cell immune evasion by decreasing the levels of CD4(+)CD25(+)Foxp3(+) Tregs and suppressing the expression of TGFbeta and IL-10 in the tumor microenvironment. PMID- 27389044 TI - Recurrent pyloric stenosis. AB - Infantile hypertrophic pyloric stenosis is the most commonly encountered surgical disease among pediatric patients. Incomplete pyloromyotomy is not uncommon complication of pyloromyotomy. However, recurrent pyloric stenosis is extremely rare. Up until now, there are only five cases reported in the English literature. We report a child with recurrent pyloric stenosis who was managed by redo pyloromyotomy. PMID- 27389043 TI - Identifying and integrating patient and caregiver perspectives for clinical practice guidelines on the screening and management of infectious microorganisms in hemodialysis units. AB - INTRODUCTION: The integration of patient and caregiver input into guideline development can help to ensure that clinical care addresses patient expectations, priorities, and needs. We aimed to identify topics and outcomes salient to patients and caregivers for inclusion in the Kidney Health Australia Caring for Australasians with Renal Impairment (KHA-CARI) clinical practice guideline on the screening and management of infectious microorganisms in hemodialysis units. METHODS: A facilitated workshop was conducted with 11 participants (patients [n = 8], caregivers [n = 3]). Participants identified and discussed potential topics for inclusion in the guidelines, which were compared to those developed by the guideline working group. The workshop transcript was thematically analyzed to identify and describe the reasons underpinning their priorities. FINDINGS: Patients and caregivers identified a range of topics already covered by the scope of the proposed guidelines and also suggested additional topics: privacy and confidentiality, psychosocial care during/after disease notification, quality of transportation, psychosocial treatment of patients in isolation, patient/caregiver education and engagement, and patient advocacy. Five themes characterized discussion and underpinned their choices: shock and vulnerability, burden of isolation, fear of infection, respect for privacy and confidentiality, and confusion over procedural inconsistencies. DISCUSSION: Patients and caregivers emphasized the need for guidelines to address patient education and engagement, and the psychosocial implications of communication and provision of care in the context of infectious microorganisms in hemodialysis units. Integrating patient and caregiver perspectives can help to improve the relevance of guidelines to enhance quality of care, patient experiences, and health and psychosocial outcomes. PMID- 27389045 TI - EGFR mutation testing using archival-stained smears in non-small cell lung carcinoma. AB - OBJECTIVE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown benefits regarding progression-free and overall survival in patients whose tumours show EGFR mutations. Most patients' lung cancer is metastatic when detected. Small tissue samples and cytological materials are widely used in diagnosis. The aim of the present study was to compare the EGFR mutation analysis results between cytology, small biopsies and resections. METHODS: Archival material for EGFR testing was reviewed. Cell blocks and/or stained smears and tissue blocks were used where appropriate. The tumour cell count and percentage were recorded as well as the DNA content. The influence of TTF-1 immunoreactivity on EGFR testing was also investigated. RESULTS: The study cohort included 300 unpaired specimens of 84 resections, 83 small biopsies and 133 cytological materials. EGFR mutation rates did not differ significantly for cytology, small biopsy and resections (P > 0.05). The higher tumour cell percentage in FNAs than in exfoliative cytology did not affect the EGFR mutation status. EGFR mutation rates were similar when either slides or cell blocks were used. Cytology slides revealed a higher tumour cell content and DNA concentration than the cell blocks. May-Grunwald-Giemsa (MGG)-stained smears had higher rates of the EGFR mutation than the Papanicolaou (Pap)-stained slides (P < 0.05). Tumours with negative immunoreactivity for TTF-1 are less likely to have an EGFR mutation (P < 0.05). CONCLUSIONS: Cytological materials can be used successfully for mutation analysis in lung cancer. PMID- 27389046 TI - Foreword. AB - The 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa required a massive international response by many partners to assist the affected countries and tested the world's readiness to respond to global health emergencies. The epidemic demonstrated the importance of improving readiness in at-risk countries and remaining prepared for Ebola and other health threats. The devastation caused by Ebola in Guinea, Liberia, and Sierra Leone is well recognized; what is less widely recognized is that in these countries more people probably died because of Ebola than from Ebola. The epidemic shut most health care systems and derailed programs to prevent and treat malaria, tuberculosis, vaccine-preventable diseases, and other conditions (1,2). PMID- 27389047 TI - Antibody-Mediated Injury to the Transplanted Liver: Receiving the Sages' Wisdom. PMID- 27389048 TI - An Unprecedented Two-Fold Nested Super-Polyrotaxane: Sulfate-Directed Hierarchical Polythreading Assembly of Uranyl Polyrotaxane Moieties. AB - The hierarchical assembly of well-organized submoieties could lead to more complicated superstructures with intriguing properties. We describe herein an unprecedented polyrotaxane polythreading framework containing a two-fold nested super-polyrotaxane substructure, which was synthesized through a uranyl-directed hierarchical polythreading assembly of one-dimensional polyrotaxane chains and two-dimensional polyrotaxane networks. This special assembly mode actually affords a new way of supramolecular chemistry instead of covalently linked bulky stoppers to construct stable interlocked rotaxane moieties. An investigation of the synthesis condition shows that sulfate can assume a vital role in mediating the formation of different uranyl species, especially the unique trinuclear uranyl moiety [(UO2 )3 O(OH)2 ](2+) , involving a notable bent [O=U=O] bond with a bond angle of 172.0(9) degrees . Detailed analysis of the coordination features, the thermal stability as well as a fluorescence, and electrochemical characterization demonstrate that the uniqueness of this super-polyrotaxane structure is mainly closely related to the trinuclear uranyl moiety, which is confirmed by quantum chemical calculations. PMID- 27389049 TI - Outcomes of Colonic Endoscopic Mucosal Resection for Large Polyps in Elderly Patients. AB - OBJECTIVE: The aim of this study is to investigate the short-term outcomes of endoscopic mucosal resection (EMR) for large colonic polyps in elderly patients (>=80 years) compared with those in younger patients (<80 years). PATIENTS AND METHODS: A total of 339 patients who underwent colon EMR >=2 cm were included. Sixty-five colon EMRs were performed on 46 patients >=80 years (Group A) and 401 resections were performed on 293 patients <80 years. Demographics, operative and short-term results were compared between the two groups. RESULTS: The median age in Group A was 83.5 years (range 80-91 years) and 66 years in Group B (range 26 79 years, P < .001). The proportion of patients with American Society of Anesthesiologists class III was significantly high in Group A (39.1% versus 17.7%, P = .001). There was no significant difference in sex ratio, body mass index, tumor size, and tumor distribution between the two groups. Median operating time was similar between the two groups (30 versus 30 minutes, P = .839). En bloc resection rate was 33.8% in Group A and 29.2% in Group B (P = .445). No anesthesia-associated adverse events or deaths occurred in both groups. Complication rate was similar between the two groups, perforation rate was 2.2% in Group A and 1.7% in Group B (P = .823), and delayed bleeding rate was 4.3% versus 3.1% (P = .650), respectively. CONCLUSIONS: Colon EMR is feasible and safe in very elderly patients. PMID- 27389050 TI - Pharmacological aspects of the safety of gliflozins. AB - Sodium-glucose transporter 2 (SGLT2) inhibitors, also known as gliflozins, are a new class of orally active drugs used in the management of type 2 diabetes. By inhibiting the SGLT responsible for the reabsorption of glucose from the kidney, their use aims primarily to induce glycosuria and, as a consequence, lower glycemic levels. However, their specific mechanism of action involves other pharmacodynamic consequences including potentially harmful adverse reactions. This manuscript reviews the physiological and pharmacological background behind inhibition of SGLTs, and discusses the pharmacological aspects of the safety of gliflozins. PMID- 27389052 TI - Untargeted Metabolomics of Tomato Plants after Root-Knot Nematode Infestation. AB - After 2 months from the infestation of tomato plants with the root-knot nematode (RKN) Meloidogyne incognita, we performed a gas chromatography-mass spectrometry untargeted fingerprint analysis for the identification of characteristic metabolites and biomarkers. Principal component analysis, and orthogonal projections to latent structures discriminant analysis suggested dramatic local changes of the plant metabolome. In the case of tomato leaves, beta-alanine, phenylalanine, and melibiose were induced in response to RKN stimuli, while ribose, glycerol, myristic acid, and palmitic acid were reduced. For tomato stems, upregulated metabolites were ribose, sucrose, fructose, and glucose, while fumaric acid and glycine were downregulated. The variation in molecular strategies to the infestation of RKNs may play an important role in how Solanum lycopersicum and other plants adapt to nematode parasitic stress. PMID- 27389051 TI - Partnership in fellowship: Comparative analysis of pediatric surgical training and evaluation of a fellow exchange between Canada and Kenya. AB - BACKGROUND: In pediatric surgery, significant differences in education and practice exist between developed and developing nations. We compared the training of senior fellows in a Canadian and a Kenyan pediatric surgery training program, and evaluated a fellow exchange between the programs. METHODS: The study was performed six years after creation of the exchange program. Areas studied included case volume and distribution, length of training, curriculum, work hours, and an estimate of service to education ratio. Perceived strengths and challenges of the exchange were investigated using questionnaires. RESULTS: Fellows at each site performed approximately 450 cases/year. Significant differences in case distribution were noted, with plastic surgery, urology and neurosurgery procedures being significantly more frequent in the Kenyan center, and neonatal, minimally invasive, and vascular access procedures being significantly more frequent in the Canadian center. All participants identified educational value in the exchange, although logistical challenges were significant. CONCLUSION: Differences exist in the training experiences of pediatric surgical fellows in Canada and Kenya, reflecting the differences in health care environment, education, and surgical practice in the two countries. The exchange program of pediatric surgical fellows tapped into this rich diversity and may be applicable to other medical and surgical specialty training programs. PMID- 27389054 TI - Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T cell lymphomas. PMID- 27389053 TI - Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). AB - Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients. PMID- 27389055 TI - Restoration of MYC-repressed targets mediates the negative effects of GM-CSF on RUNX1-ETO leukemogenicity. AB - Granulocyte macrophage-colony-stimulating factor (GM-CSF) signaling regulates hematopoiesis and immune responses. CSF2RA, the gene encoding the alpha-subunit for GM-CSF, is significantly downregulated in t(8;21) (RUNX1-ETO or RE) leukemia patients, suggesting that it may serve as a tumor suppressor. We previously reported that GM-CSF signaling is inhibitory to RE leukemogenesis. Here we conducted gene expression profiling of primary RE hematopoietic stem/progenitor cells (HSPCs) treated with GM-CSF to elucidate the mechanisms mediating the negative effects of GM on RE leukemogenicity. We observed that GM treatment of RE HSPCs resulted in a unique gene expression profile that resembles primary human cells undergoing myelopoiesis, which was not observed in control HSPCs. Additionally, we discovered that GM-CSF signaling attenuates MYC-associated gene signatures in RE HSPCs. In agreement with this, a functional screen of a subset of GM-CSF-responsive genes demonstrated that a MYC inhibitor, MXI1 (Max interactor 1), reduced the leukemic potential of RE HSPCs and t(8;21) acute myeloid leukemia (AML) cells. Furthermore, MYC knockdown and treatment with the BET (bromodomain and extra terminal domain) inhibitor JQ1 reduced the leukemic potential of t(8;21) cell lines. Altogether, we discovered a novel molecular mechanism mediating the GM-CSF-induced reduction in leukemic potential of RE cells, and our findings support MYC inhibition as an effective strategy for reducing the leukemogenicity of t(8;21) AML. PMID- 27389056 TI - Exome sequencing identifies highly recurrent somatic GATA2 and CEBPA mutations in acute erythroid leukemia. AB - Acute erythroid leukemia (AEL), characterized by a predominant erythroid proliferation, is a subtype of acute myelogenous leukemia. The genetic basis of AEL remains poorly defined. Through whole-exome sequencing, we identified high frequencies of mutations in CEBPA (32.7%), GATA2 (22.4%), NPM1 (15.5%), SETBP1 (12.1%) and U2AF1 (12.1%). Structure prediction analysis revealed that most of the GATA2 mutations were located at the DNA-binding N-terminal zinc-finger near the DNA-binding interface, suggesting that mutations could result in at least partial inactivation of GATA2 protein. On co-transfection of a GATA-responsive reporter construct together with plasmids expressing either GATA2 wild-type or GATA2 ZF1 mutants (P304H, L321P and R330X) in 293T cells, we found a reduced transcriptional activation in cells transfected with GATA2 mutants. To determine whether reduced GATA2 function is involved in leukemogenesis of AEL, we transfected 32D cells with GATA2 mutants and evaluated the impact of GATA2 mutations on erythroid differentiation. Our data revealed an increased expression of erythroid-related antigens Ter-119, beta-globin and betah1-globin, as well as increased hemoglobin positivity in 32D cells transfected with GATA2 mutants compared with control cells. Our results suggest that the decline of GATA2 resulting from mutations contributes to the erythroid commitment, differentiation and the development of AEL. PMID- 27389057 TI - Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma. AB - Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information. We found recurrent mutations of miR-142, which has not been previously been reported to be mutated in FL/tFL. The genes most frequently mutated in tFL included KMT2D (MLL2), CREBBP, EZH2, BCL2 and MEF2B. Many recurrently mutated genes are involved in epigenetic regulation, the Janus-activated kinase-signal transducer and activator of transcription (STAT) or the nuclear factor-kappaB pathways, immune surveillance and cell cycle regulation or are TFs involved in B-cell development. Of particular interest are mutations and CNAs affecting S1P-activated pathways through S1PR1 or S1PR2, which likely regulate lymphoma cell migration and survival outside of follicles. Our custom gene enrichment panel provides high depth of coverage for the study of clonal evolution or divergence. PMID- 27389059 TI - Goserelin toxicities and preferences for ovarian suppression method in pre menopausal women with breast cancer. AB - BACKGROUND: Goserelin, a form of medical ovarian suppression, is an effective treatment for pre-menopausal women with breast cancer (PMBC). Meta-analysis data showed that similar efficacy is achieved with medical ovarian suppression and non pharmacological ovarian suppression (NPOS) - oophorectomy or ovarian irradiation. The acceptance rate of NPOS remains low. AIMS: This study explored the reported toxicities of PMBC women and their preferred ovarian suppression method whilst on goserelin. METHODS: A postal survey consisting of 22 study-specific questions was sent to PMBC women who received goserelin at the Flinders Medical Centre. RESULTS: Nineteen women were identified from the database; 12 versus 7 women received goserelin in the adjuvant versus metastatic setting respectively. Thirteen (68.4%) responded to the survey. Women in the adjuvant cohort were more likely to report toxicities. The most common were hot flushes (100% vs 50% P = 0.033), myalgia/arthralgia (71.4% vs 16.7%, P = 0.048) and decreased libido (57/1% vs 16.7%, P = 0.135). NPOS was recalled to be offered to five (38.5%) women, with acceptance by one BRCA2 carrier. NPOS was declined initially due to fear of procedure, surgical/anaesthetic risk, invasiveness and planned future pregnancies. If given the option, upfront oophorectomy was indicated in seven (53.8%) women due to inconveniences with monthly goserelin. CONCLUSION: Half of PMBC women indicated a preference to NPOS, but only a minority recollected NPOS being discussed. Inconvenience with monthly goserelin is the main driver toward a preference of favouring NPOS. Clarification from larger trials that research patients' decision process and preferences regarding ovarian suppression is needed to validate our findings. PMID- 27389060 TI - A novel method for sexing day-old chicks using endoscope system. AB - Sexing day-old chicks is important for layer and broiler production. A novel method for sexing day-old chicks was developed using an endoscope system. The probe of the endoscope was inserted from the cloaca into the intestine of a chick, and the presence of testes or ovary was observed through the wall of the intestine. The picture image was displayed on the monitor. Sexing was performed in White Leghorn (WL) and Rhode Island Red (RIR) chicks using this new system. The accuracy of sexing was 91.1% in WL chicks and 88.3% in RIR chicks, confirmed by observing gonads after laparotomy or appearances at 80 d of age. Accuracy of sexing male chicks (95.0%) was higher than that of female chicks (86.0%). The overall accuracy of sexing was 90.2% in the present study, and the accuracy would be improved by continuous training in the handling of the endoscope. The endoscope system devised in this study requires no specific skills and anyone can perform sexing of chicks after short-term training. PMID- 27389061 TI - Effect of long-term selection for egg production on eggshell quality of Japanese quail (Coturnix japonica). AB - An experiment was conducted to evaluate egg quality and ultrastuctural measurements of eggshell using a Scanning Electron Microscope (SEM) in 2 lines (selected and control) of Japanese quail. A selection program was applied over 22 consecutive generations for higher egg production and lower broken egg percentage. The results revealed that the females of the selected line produced significantly (P < 0.01) higher egg mass compared to that of the control line. Also, the selection procedure significantly improved feed conversion ratio. The eggshells of the selected line had a higher breaking strength compared to those of the control line, although there was no difference between them in shell thickness. Significantly higher wet (P < 0.01) and dry (P < 0.05) eggshell percentages were found in the selected line. In general, the eggshells of the selected line had a lower total score (good) of ultrastructural evaluation compared to the control line. According to scanning electron microscope data, the incidence of certain structural variants was more common in eggshells of the control line suggesting poor shell strength. The incidence of alignment was more prevalent in control eggshells compared to selected ones, suggesting lower resistance to breakage. Late fusion and large interstitial spaces of the palisade layer indicating decreased resistance to fracture were observed in control eggshells. It could be concluded that the improvement eggshell quality may be caused by the long-term selection for lower cracked and broken egg rates from generation to generation. PMID- 27389058 TI - Emerging therapies provide new opportunities to reshape the multifaceted interactions between the immune system and lymphoma cells. AB - The acquisition of a complete neoplastic phenotype requires cancer cells to develop escape mechanisms from the host immune system. This phenomenon, commonly referred to as 'immune evasion,' represents a hallmark of cancers and results from a Darwinian selection of the fittest tumor clones. First reported in solid tumors, cancer immunoescape characterizes several hematological malignancies. The biological bases of cancer immunoescape have recently been disclosed and include: (i) impaired human leukocyte antigen-mediated cancer cell recognition (B2M, CD58, CTIIA, CD80/CD86, CD28 and CTLA-4 mutations); (ii) deranged apoptotic mechanisms (reduced pro-apoptotic signals and/or increased expression of anti-apoptotic molecules); and (iii) changes in the tumor microenvironment involving regulatory T cells and tumor-associated macrophages. These immune-escape mechanisms characterize both Hodgkin and non-Hodgkin (B and T cell) lymphomas and represent a promising target for new anti-tumor therapies. In the present review, the principles of cancer immunoescape and their role in human lymphomagenesis are illustrated. Current therapies targeting these pathways and possible applications for lymphoma treatment are also addressed. PMID- 27389062 TI - Rapid and sensitive detection of Mycoplasma synoviae by an insulated isothermal polymerase chain reaction-based assay on a field-deployable device. AB - Mycoplasma synoviae (MS), causing respiratory diseases, arthritis, and eggshell apex abnormalities in avian species, is an important pathogen in the poultry industry. Implementation of a biosecurity plan is important in MS infection management. Working on a field-deployable POCKITTM device, an insulated isothermal polymerase chain reaction (iiPCR) assay has a potential for timely MS detection on the farm. The MS iiPCR assay had limit of detection 95% of about 9 genome equivalents by testing serial dilutions of a standard DNA. The detection endpoint of the assay for detection of MS genomic DNA was comparable to a reference real-time PCR. The assay did not crossreact with other important avian pathogens, including avian reovirus, Mycoplasma gallisepticum, Staphylococcus aureus, Escherichia coli, Pasteurella multocida, and Salmonella Pullorum. When 92 synovial fluid and respiratory tract swab samples collected from chickens, turkeys, and geese suspected of MS infection were tested, the clinical performance of the MS iiPCR had 97.8% agreement (Cohen's kappa value, 0.95) with that of the reference real-time PCR. In conclusion, the MS iiPCR/POCKITTM system, working with field-deployable manual or automatic nucleic acid extraction methods, has potential to serve as a rapid and sensitive on-site tool to facilitate timely detection of MS. PMID- 27389063 TI - Effect of pre- and post-marination aging on meat quality attributes of early deboned (2 h postmortem) broiler breast fillets. AB - Marination is an effective method that can be used to improve the tenderness of early deboned breast fillets. The present study was designed to evaluate the effect of pre- and post-marination aging of 2 h postmortem (PM) deboned chicken fillets to get optimum meat quality. In this study, a total of 300 broilers (43 to 46 d of age) were processed using an in-line system and deboned at 2 h PM. Fillets were marinated, at either 2.5, 4, 6, 8 or 24 h PM, using vacuum tumbling (20 min) with a 15% marinade (final concentration of 0.5% salt and 0.45% phosphate). A non-marinated control (CON) was included. The left (HOLD) fillets were aged (held at 4 degrees C for 24 h) prior to freezing post-marination while the right (NO HOLD) fillets were frozen immediately after marination to simulate various commercial practices. Marination pickup (MPU), total marinade retained after thawing (TMR), total purge loss after thawing (TPL), cook loss (CL), and Meullenet-Owens Razor Shear energy (MORSE) values were measured. Both in HOLD and NO HOLD fillets, there was an increase (P < 0.05) in MPU and TMR as the time of marination increased from 2.5 to 24 h PM. Furthermore, the HOLD fillets had a higher (P < 0.05) TPL when compared to the NO HOLD group. There was a higher (P < 0.05) CL for the CON fillets when compared to all marinated fillets suggesting that marination resulted in better water holding capacity. However, both in HOLD and NO HOLD groups, the MORSE values for the marinated fillets decreased (P < 0.05) from 4 h PM onwards, with 8 and 24 h PM having lower (P < 0.05) values than all other treatments. The results of this study suggest that pre-marination aging (aging after deboning prior to marination) of early (2 h PM) deboned fillets to 8 h PM can provide better tumble marination pickup and retention as well as tenderness (or lower shear values). PMID- 27389064 TI - Parenteral lorazepam's unavailability in Australia and the impact for catatonic patients. PMID- 27389065 TI - Trichotillomania and other 'manias': A lesson in inconsistency, selective concern about stigma and political correctness. PMID- 27389066 TI - Have we underestimated the possibility of cultural differences affecting prescription of hormone treatment for individuals with gender dysphoria? PMID- 27389067 TI - Restoring Study 329: Paroxetine neither effective nor safe for adolescents. PMID- 27389068 TI - PLGA nanoparticles for ocular delivery of loteprednol etabonate: a corneal penetration study. AB - The purpose of the present study was to develop loteprednol etabonate (LE) loaded poly(d,l-lactide co-glycolide) (PLGA) nanoparticles (NPs) and study their penetration profile into the excised goat cornea. In the present study, LE loaded PLGA NPs were prepared by solvent evaporation with high speed homogenization method and the penetration profile was studied using confocal laser scanning microscopy (CLSM). Rhodamine (Rd) was used as a fluorescent marker to prepare Rd LE-PLGA-NPs. The NPs were characterized for particle size, X-ray diffraction (XRD), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), drug entrapment, and permeation profile. Intense fluorescence observed across the depths of goat corneal tissue suggested an improved penetration profile of NPs. The entrapment efficiency and mean diameter of the optimized formulation (F5) were found to be 96.31 +/- 1.68% and 167.6 +/- 0.37 nm, respectively. These findings indicate that LE loaded PLGA NPs may serve as a potential drug carrier for ocular administration in eye disease. PMID- 27389069 TI - Endocidal Regulation of Secondary Metabolites in the Producing Organisms. AB - Secondary metabolites are defined as organic compounds that are not directly involved in the normal growth, development, and reproduction of an organism. They are widely believed to be responsible for interactions between the producing organism and its environment, with the producer avoiding their toxicities. In our experiments, however, none of the randomly selected 44 species representing different groups of plants and insects can avoid autotoxicity by its endogenous metabolites once made available. We coined the term endocides (endogenous biocides) to describe such metabolites that can poison or inhibit the parent via induced biosynthesis or external applications. Dosage-dependent endocides can selectively induce morphological mutations in the parent organism (e.g., shrubbiness/dwarfism, pleiocotyly, abnormal leaf morphogenesis, disturbed phyllotaxis, fasciated stems, and variegation in plants), inhibit its growth, development, and reproduction and cause death than non-closely related species. The propagule, as well as the organism itself contains or produces adequate endocides to kill itself. PMID- 27389070 TI - Compact characterization of liquid absorption and emission spectra using linear variable filters integrated with a CMOS imaging camera. AB - A compact analysis platform for detecting liquid absorption and emission spectra using a set of optical linear variable filters atop a CMOS image sensor is presented. The working spectral range of the analysis platform can be extended without a reduction in spectral resolution by utilizing multiple linear variable filters with different wavelength ranges on the same CMOS sensor. With optical setup reconfiguration, its capability to measure both absorption and fluorescence emission is demonstrated. Quantitative detection of fluorescence emission down to 0.28 nM for quantum dot dispersions and 32 ng/mL for near-infrared dyes has been demonstrated on a single platform over a wide spectral range, as well as an absorption-based water quality test, showing the versatility of the system across liquid solutions for different emission and absorption bands. Comparison with a commercially available portable spectrometer and an optical spectrum analyzer shows our system has an improved signal-to-noise ratio and acceptable spectral resolution for discrimination of emission spectra, and characterization of colored liquid's absorption characteristics generated by common biomolecular assays. This simple, compact, and versatile analysis platform demonstrates a path towards an integrated optical device that can be utilized for a wide variety of applications in point-of-use testing and point-of-care diagnostics. PMID- 27389071 TI - To the Editor. PMID- 27389072 TI - Echinoderm systems for gene regulatory studies in evolution and development. AB - One of the main challenges in Evolutionary Developmental Biology is to understand to which extent developmental changes are driven by regulatory alterations in the genomic sequence. In the recent years, the focus of comparative developmental studies has moved towards a systems biology approach providing a better understanding of the evolution of gene interactions that form the so called Gene Regulatory Networks (GRN). Echinoderms provide a powerful system to reveal regulatory mechanisms and within the past decade, due to the latest technological innovations, a great number of studies have provided valuable information for comparative GRN analyses. In this review we describe recent advances in evolution of GRNs arising from echinoderm systems, focusing on the properties of conserved regulatory kernels, circuit co-option events and GRN topological rearrangements. PMID- 27389073 TI - Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis. AB - New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first-line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first-line treatment including induction therapy, cytotoxic stem cell mobilization and high-dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34(+) HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long-term HSPC proliferation in vitro. We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF-beta signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long-term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF-beta signaling pathway. PMID- 27389075 TI - The role of the dipolar neighborhood on the relaxation dynamics of multichromophoric merocyanines. AB - The interactions between different chromophores within a molecular system are crucial to comprehend relaxation dynamics, regardless if one deals with small molecules or larger systems like polymers or aggregates. We investigate a series of merocyanine molecules that contain one, two or three highly dipolar (MUg = 13.1 D) dyes in close vicinity to study the influence and origin of interactions, e.g., electronic, vibronic, or the formation of excitons. Relaxation dynamics are probed via transient absorption and coherent two-dimensional spectroscopy. Furthermore, we derive a general relaxation model which can be applied for all merocyanines under investigation and can be used as a reference point for other dipolar donor-acceptor dyes. The intramolecular charge-transfer state of the monomeric merocyanine is stabilized by dipolar neighbor molecules in the bis- and tris-chromophoric dyes. PMID- 27389074 TI - Influence of Resting Venous Blood Volume Fraction on Dynamic Causal Modeling and System Identifiability. AB - Changes in BOLD signals are sensitive to the regional blood content associated with the vasculature, which is known as V0 in hemodynamic models. In previous studies involving dynamic causal modeling (DCM) which embodies the hemodynamic model to invert the functional magnetic resonance imaging signals into neuronal activity, V0 was arbitrarily set to a physiolog-ically plausible value to overcome the ill-posedness of the inverse problem. It is interesting to investigate how the V0 value influences DCM. In this study we addressed this issue by using both synthetic and real experiments. The results show that the ability of DCM analysis to reveal information about brain causality depends critically on the assumed V0 value used in the analysis procedure. The choice of V0 value not only directly affects the strength of system connections, but more importantly also affects the inferences about the network architecture. Our analyses speak to a possible refinement of how the hemody-namic process is parameterized (i.e., by making V0 a free parameter); however, the conditional dependencies induced by a more complex model may create more problems than they solve. Obtaining more realistic V0 information in DCM can improve the identifiability of the system and would provide more reliable inferences about the properties of brain connectivity. PMID- 27389076 TI - Tension hydropneumopericardium following laparoscopic Nissen fundoplication. PMID- 27389078 TI - Complication in diabetic nephropathy. AB - BACKGROUND: Diabetic kidney disease is the most common cause of chronic kidney disease, leading to end-stage renal disease (ESRD) and premature death. In addition, it negatively affects a patient's quality of life and social environment, and poses a burden on national health care budgets. Although various therapeutic approaches, such as hypoglycemic agents, antihypertensive drugs, and renin-angiotensin system inhibitors, have been tried to slow the progression of nephropathy, the number of patients with diabetic kidney disease continues to rise with the prevalence of type 2 diabetes mellitus. Thus, early identification of patients at risk of developing diabetic nephropathy and initiation of appropriate therapy is important to improve patient outcomes. In end stage renal disease (ESRD), diabetic nephropathy is the main cause considered from other diseases. PMID- 27389077 TI - Relationship between functional capacity and health-related quality of life of patients with type-2 diabetes. AB - AIMS: Physical function is a determinant of survival in chronic diseases, however, little is known about functional capacity (FC) and self-reported health status of patients with type-2 diabetes (T2D). This study investigated the relationship between FC and health related quality of life (HRQoL) of patients with T2D. MATERIALS AND METHODS: This cross-sectional survey recruited 150 patients with T2D from a Nigerian university teaching hospital using purposive sampling technique. Socio-demographic and physical characteristics were assessed. FC and HRQoL including physical and mental health component summary (PCS and MCS) were assessed using the six minute walk test (6MWT) and Short-Form (SF-12) questionnaire respectively. Maximum oxygen consumption (VO2 max) was estimated, pre and post 6MWT cardiovascular parameters and fasting blood glucose (FBG) were assessed. Data were analyzed using descriptive and inferential statistics. Alpha level was set at p<0.05. RESULTS: There were 83(55.3%) women, means of age and FBG of participants were 64.2+/-8.7years and 7.4+/-2.4mmol/L respectively. The means of 6-min walk distance (6-MWD) and estimated VO2 max were 341.55+/-41.82m and 9.2+/-0.7mL/kg/min respectively. Significant differences were found between pre and post HR (t=-44.71; p=0.001), SBP (t=-38.38; p=0.001) and DBP (t=-38.58; p=0.001) following 6MWT. The means of PCS and MCS of HRQoL were 48.67+/-5.51 and 58.39+/-2.86 respectively. There were significant correlations between FC and each of PCS (r=0.678; p=0.001) and MCS (r=0.211; p=0.009). CONCLUSION: Patients with T2D demonstrated low functional capacity and reduced HRQoL. Significant relationship exists between FC and physical and mental component summary of HRQoL. Exercise intervention to improve FC and HRQoL were recommended. PMID- 27389079 TI - Could omega-3 fatty acids a therapeutic treatment of the immune-metabolic consequence of intermittent hypoxia in obstructive sleep apnea? AB - Obesity and Obstructive sleep Apnea (OSA) seems to bi-directional; obesity itself increases the risk of OSA, but on the other hand, OSA may also predispose the individuals to weight gain, both obesity and OSA share a common immune-metabolic link state which have a synergistic effect on the activation of inflammation, insulin resistance and dyslipidemia, and cardiovascular disease. The Immune metabolic role of omega-3 fatty acids Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA), which capable of modulating both metabolic and immune process, which may decrease pro-inflammatory cytokines, insulin resistance, and dyslipidemia. To date, no study in humans suffering from OSA and omega-3 fatty acids has been performed. Hence, the objective of this review aimed to discussing the link between immune-metabolic consequences related to intermittent hypoxia and does Omega-3 fatty acids a therapeutic treatment for co morbidity associated with obstructive sleep apnea. PMID- 27389081 TI - Evaluating dietary patterns: the role of reduced rank regression. AB - PURPOSE OF REVIEW: The purpose of review is to present methodological issues as well as most relevant recent developments on the application of a statistical method to derive dietary patterns: reduced rank regression (RRR). RRR can be used efficiently in nutritional epidemiology to identify dietary patterns associated with selected response variables that have known relations with a disease outcome of interest. This has the advantage of building on a priori knowledge of biological relations, by including plausible intermediates between diet and the outcome of interest. RECENT FINDINGS: This statistical method has been applied first in nutritional epidemiology about 1 decade ago. Since then, more than 60 publications were published applying the RRR. This method is considerably dependent on an adequate selection of response variables. These response sets were most often a combination of nutrients or of selected endogenous biomarkers. But also variables of intermediate clinical phenotype or contaminants were selected. However, applying this method, several methodological issues, such as, for example, selection of responses, simplification, and validation of the derived pattern should be taken into account. SUMMARY: RRR is a modern statistical method to derive dietary patterns that can be used to test specific hypothesis on pathways from diet to development of a disease. PMID- 27389080 TI - Cerebral microbleeds in early Alzheimer's disease. AB - We hypothesize that cerebral microbleeds (CMB) in patients with different neuropsychological profiles (amnestic or non-amnestic) and MRI features of vascular damage could provide important information on the underlying pathological process in early Alzheimer's disease. The study was performed at two trial sites. We studied 136 outpatients with cognitive decline. MRI was performed using a magnetic field of 1.5 and 3 T. Neuropsychological assessment included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Addenbrooke's Cognitive Examination (ACE-R), Cambridge Cognitive Examination battery (CAMCOG) (Part 3), Clock Drawing Test, fluency test and the visual memory test (SCT). CSF was examined for standard parameters such as tau, phosphorylated tau, amyloid-beta 1-40 and 42 and Qalbumin, in accordance with established protocols and genotype. In 61 patients (45 %), at least 1 CMB was found. Most of the CMBs were described in the amnestic profile (67 %). In 86 % of the cases, multiple CMB were observed. The ratio of Abeta1-40/42 in non-amnestic patients with CMB was significantly lower (mean 0.6) than in patients without CMB (mean 1.2). A notable difference in the albumin ratio as an indicator of the BBB was observed between groups with and without CMB. In the CMP-positive group, the E2 genotype was observed more frequently, and the E4 genotype less frequently, than in the CMB-negative group. Based on the cerebrospinal fluid-serum albumin ratio, we were able to show that patients with CMB present several features of BBB dysfunction. According to logistic regression, the predictive factors for CMB in patients with cognitive decline were age, WMHs score and albumin ratio. We found a significant reduction in the Abeta-amyloid ratio in the non-amnestic profile group with CMB (particularly in the cortical region) in comparison to those without CMB. While this is an interesting finding, its significance needs to be assessed in a prospective follow-up. PMID- 27389082 TI - Foods and their components promoting gastrointestinal cancer. AB - PURPOSE OF REVIEW: Cancer represents one of the most feared diseases. Despite an increasing number of available scientific data, most people remain unaware of those basic dietary and healthy lifestyle measures, which might reduce their risk to develop cancer. Environmental factors, diet, and lifestyle play a crucial role in the development of several different neoplastic diseases, particularly gastrointestinal cancer. In this article, we aimed at focusing on foods and their components able to increase gastrointestinal cancer risk. RECENT FINDINGS: During the last few years, major emphasis has been addressed on the relation between red meat and gastrointestinal cancer. Many potential mechanisms linked red meat consumption and cancer risk, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Other chemical substances, contaminating food, such as acrylamide, showed gastrointestinal carcinogenic properties. SUMMARY: Correct diet and lifestyle are clinically relevant strategies in preventing gastrointestinal cancer. In the fight against cancer, nutritional educative intervention programs are necessary to spread the knowledge on healthy eating and appropriate nutrition to reduce cancer risk. PMID- 27389083 TI - Prediabetes and risk of diabetes and associated complications: impaired fasting glucose versus impaired glucose tolerance: does it matter? AB - PURPOSE OF REVIEW: The purpose of this review is to summarize the distinct metabolic and pathophysiologic phenotype of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and the subsequent clinical implications with regard to future type 2 diabetes mellitus (T2DM) and cardiovascular risk. RECENT FINDINGS: Both IFG and IGT manifest the two core defects of T2DM, that is, insulin resistance and beta-cell dysfunction. However, the site of insulin resistance and shape of beta-cell dysfunction differ. These distinct metabolic and pathophysiologic phenotypes explain the greater cardiovascular disease (CVD) risk associated with an increase in the 2-h plasma glucose concentration, that is, IGT compared with an increase in the fasting plasma glucose (FPG) concentration, that is, IFG. Moreover, the increase in future T2DM risk in IFG study participants is, at least in part, explained by the strong correlation between the increase in FPG and the increase in 2-h plasma glucose concentration. SUMMARY: Last, recent studies have reported the presence of diabetic microvascular complications, that is, retinopathy and neuropathy, at the IGT stage.Thus, a glucose load (e.g. oral glucose tolerance test) is required in study participants with elevated FPG concentration to accurately assess their future risk for T2DM, as well as their risk for CVD to identify the subgroup of IFG who are at greater risk and subject them to an intervention program to decrease their future T2DM and CVD risk. PMID- 27389084 TI - Impact of lorcaserin on glycemic control in overweight and obese patients with type 2 diabetes: analysis of week 52 responders and nonresponders. AB - OBJECTIVES: Treatment guidelines for type 2 diabetes mellitus (T2DM) suggest weight loss as a means to maintain glycemic control. Lorcaserin has been approved for chronic weight management in the United States as an adjunct to a reduced calorie diet and exercise, and the previous phase 3 Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus (BLOOM-DM) study has shown that, in addition to weight loss, lorcaserin is associated with improvements in glycemic parameters. In this post hoc analysis of the BLOOM-DM trial, the relationship between responder status (patients achieving >=5% weight loss at Week 52) and glycemic and cardiometabolic parameters is evaluated. METHODS: Data are presented for patients receiving lorcaserin 10 mg twice daily or placebo for 52 weeks. RESULTS: More than twice as many patients receiving lorcaserin plus diet and exercise counseling were classified as Week 52 responders compared to those receiving diet and exercise counseling alone (37.5% vs. 16.1%, respectively; p < 0.001), and lorcaserin Week 52 responders had greater improvements vs. placebo Week 52 responders in FPG (-38.1 mg/dL vs. -26.0 mg/dL) and HbA1c (-1.3% vs. -1.0%). Furthermore, more lorcaserin-treated Week 52 responders decreased the number of concomitant oral antidiabetic medications (OADs) used, and fewer increased the number of OADs used, compared to placebo. Unexpectedly, lorcaserin Week 52 nonresponders also had substantial reductions in glycemic levels, despite very modest weight loss. CONCLUSIONS: These data support lorcaserin use in overweight and obese patients with T2DM to promote weight loss and facilitate glycemic control. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT00603291. PMID- 27389085 TI - Adalimumab and Azathioprine Combination Therapy for Crohn's Disease: A Shining Diamond? PMID- 27389086 TI - Heat and moisture exchanger use reduces in-hospital complications following total laryngectomy: a case-control study. AB - BACKGROUND: Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients' respiratory performance in addition to their quality of life. METHODS: The case records of 48 patients undergoing total laryngectomy were reviewed and data concerning demographics, surgical details, post-operative care requirements and adverse events was retrieved. Post hoc analysis of the case patients was undertaken to identify any benefit of using a heat and moisture exchanger (HME) system with particular reference to post-operative respiratory outcomes. RESULTS: There was no significant difference between case and control subjects based on demographics, extent of surgery or need for flap repair. 16 patients had used a HME and 32 patients had used external humidification (EH). Of those experiencing mucous plugging, only 3/24 (12.5 %) had used a HME system, in contrast to 21/24 (87.5 %) who used EH (Chi square = 9.375, p = 0.002). The odds ratio of having an adverse event if not using HME was 8.27 (CI = 1.94 - 35.71). Use of HME also significantly reduced the number of days requiring physiotherapy (1.75 days vs. 3.20 days, p = 0.034). CONCLUSION: Use of an HME system can reduce in-hospital complications, in particular episodes of mucus plugging, and post-operative care requirements. Furthermore, there is a cost benefit to using HME systems that warrants more widespread introduction of these devices in head and neck surgery centers. PMID- 27389087 TI - SHP2 and UGP2 are Biomarkers for Progression and Poor Prognosis of Gallbladder Cancer. AB - Biomarkers for the diagnosis, prognosis, and targeting therapy of gallbladder cancers are not clinically available. This study demonstrated that the percentage of cases with positive SHP2 and UGP2 expression significantly correlated with the percentage of cases with positive vimentin, beta-catenin, MMP2, MMP9, and Ki-67 expression, large tumor size, high TNM stage, lymph node metastasis, and survival in patients with adenocarcinomas and squamous cell/adenosquamous carcinomas. Positive SHP2 and UGP2 expression are independent poor-prognostic factors in both types of tumors. Our study suggested that positive SHP2 and UGP2 expression correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer. PMID- 27389088 TI - Chinese medicine for outcomes in colorectal cancer patients: A retrospective clinical study. AB - OBJECTIVE: To investigate the effect of Chinese medicine (CM) on survival of patients with stage II and III colorectal cancer (CRC). METHODS: A total of 295 patients who received chemotherapy were assigned to Group 1. The other 171 patients received the same chemotherapy treatment combined with the usage of CM Jianpi Jiedu Formula (, JPJD) for more than 3 months (Group 2). Patients' survival time, relapse and metastasis, and cause of death were observed. Cox proportional hazard regression models were established for the analysis of the effect of independent factors on the survival prognosis of patients with CRC. RESULTS: The survival rate of patients in Group 2 was higher than that of Group 1 (P<0.05). Compared with Group 1, the mean survival time was prolonged by 5.594 months and the median survival time was prolonged by 6 months in Group 2 (P=0.004). Cox regression analysis indicated that CM combined with chemotherapy provided signifificant protective effect, as observed with the improvements in the survival rates of CRC patients (P<0.01). CONCLUSION: CM can improve the survival rate in patients with stage II and III CRC. PMID- 27389089 TI - Identification of human serum protein targets of Qianggu Decoction () in primary type I osteoporosis based on tandem mass tag labeling and liquid chromatography tandem mass spectrometry technology. AB - OBJECTIVE: To investigate the serum protein targets of Qianggu Decoction (, QGD) on treating osteoporosis by the proteomics analysis using tandem mass tag (TMT) and liquid chromatographytandem mass spectrometry (LC-MS/MS). METHODS: Twenty serum protein samples were recruited (10 patients with primary type I osteoporosis before and after QGD treatment) and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out. RESULTS: A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology (GO) annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen (AGT), stromelysin-1 (MMP3), heparanase (HPSE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11 (TNFSF11) families. CONCLUSIONS: The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type I osteoporosis. PMID- 27389090 TI - Associations between lifetime potentially traumatic events and chronic physical conditions in the South African Stress and Health Survey: a cross-sectional study. AB - BACKGROUND: This study examined the association between the type, and cumulative number of lifetime potentially traumatic events (PTEs), and chronic physical conditions, in a South African sample. PTE exposures have been associated with an increased risk for a wide range of chronic physical conditions, but it is unclear whether psychiatric disorders mediate this association. Given the established differences in trauma occurrence, and the epidemiology of posttraumatic stress disorder (PTSD) in South Africa relative to other countries, examining associations between PTEs and chronic physical conditions, particularly while accounting for psychiatric comorbidity is important. METHODS: Data were drawn from the South African Stress and Health Study, a cross-sectional population representative study of psychological and physical health of South African adults. Twenty-seven PTEs, based on the World Health Organization Composite International Diagnostic Interview Version 3.0, DSM-IV PTSD module were grouped into seven PTE types (war events, physical violence, sexual violence, accidents, unexpected death of a loved one, network events, and witnessing PTEs). Five clusters of physical conditions (cardiovascular, arthritis, respiratory, chronic pain, and other health conditions) were examined. Logistic regressions assessed the odds of reporting a physical condition in relation to type and cumulative number of PTEs. Cochran-Armitage test for trend was used to examine dose-response effect of cumulative PTEs on physical conditions. RESULTS: After adjusting for sociodemographic variables and psychiatric disorders, respondents with any PTE had increased odds of all assessed physical conditions, ranging between 1.48 (95 % CI: 1.06-2.07) for arthritis and 2.07 (95 % CI: 1.57-2.73) for respiratory conditions, compared to those without PTE exposure. Sexual violence, physical violence, unexpected death of a loved one, and network PTEs significantly increased the odds of all or nearly all the physical conditions assessed. There was a dose-response relationship between number of PTEs and increased odds of all physical conditions. CONCLUSIONS: Results from this study, the first in an African general population, are consistent with other population-based studies; PTEs confer a broad-spectrum risk for chronic physical conditions, independent of psychiatric disorders. These risks increase with each cumulative PTE exposure. Clinically, comprehensive evaluations for risk of mental and physical health morbidities should be considered among PTE survivors. PMID- 27389091 TI - Perioperative evaluation of respiratory impedance using the forced oscillation technique: a prospective observational study. AB - BACKGROUND: Intravascular fluid shifts, mechanical ventilation and inhalational anesthetic drugs may contribute to intraoperative lung injury. This prospective observational study measured the changes in respiratory impedance resulting from inhalational anesthesia and mechanical ventilation in adults undergoing transurethral resection of bladder tumors. The components of respiratory impedance (resistance and reactance) were measured using the forced oscillation technique (FOT). METHODS: Respiratory resistance at 5 Hz (R5) and 20 Hz (R20), respiratory reactance at 5 Hz (X5), resonant frequency (Fres) and area of low reactance (ALX) were measured before and immediately after surgery in 30 adults. In addition, preoperative vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1.0) were evaluated using spirometry. All patients were intubated with an endotracheal tube and were mechanically ventilated, with anesthesia maintained with sevoflurane. Pre- and postoperative FOT measurements were compared using Wilcoxon paired rank tests, and the relationships between FOT measurements and preoperative spirometry findings were determined by Spearman's rank correlation analysis. RESULTS: Twenty six patients were included in the final analysis: postoperative FOT could not be performed in four because of postoperative restlessness or nausea. The mean duration of surgery was 47 min. All components of respiratory resistance deteriorated significantly over the course of surgery, with median increases in R5, R20, and R5-R20 of 1.67 cmH2O/L/s (p < 0.0001), 1.28 cmH2O/L/s (p < 0.0001) and 0.46 cmH2O/L/s (p = 0.0004), respectively. The components of respiratory reactance also deteriorated significantly, with X5 decreasing 1.7 cmH2O/L/s (p < 0.0001), Fres increasing 5.57 Hz (p < 0.0001) and ALX increasing 10.51 cmH2O/L/s (p < 0.0001). There were statistically significant and directly proportional relationships between pre- and postoperative X5 and %VC, %FEV1.0 and %FVC, with inverse relationships between pre- and postoperative Fres and ALX. CONCLUSIONS: All components measured by FOT deteriorated significantly after a relatively short period of general anesthesia and mechanical ventilation. All components of resistance increased. Of the reactance components, X5 decreased and Fres and ALX increased. Pre- and postoperative respiratory reactance correlated with parameters measured by spirometry. TRIAL REGISTRATION: JMA-IIA00136 . PMID- 27389093 TI - Alzheimer disease: Could tear proteins be biomarkers for Alzheimer disease? PMID- 27389094 TI - Stroke: How good is aspirin for patients with acute brain ischaemia? PMID- 27389092 TI - Chronic migraine: risk factors, mechanisms and treatment. AB - Chronic migraine has a great detrimental influence on a patient's life, with a severe impact on socioeconomic functioning and quality of life. Chronic migraine affects 1-2% of the general population, and about 8% of patients with migraine; it usually develops from episodic migraine at an annual conversion rate of about 3%. The chronification is reversible: about 26% of patients with chronic migraine go into remission within 2 years of chronification. The most important modifiable risk factors for chronic migraine include overuse of acute migraine medication, ineffective acute treatment, obesity, depression and stressful life events. Moreover, age, female sex and low educational status increase the risk of chronic migraine. The pathophysiology of migraine chronification can be understood as a threshold problem: certain predisposing factors, combined with frequent headache pain, lower the threshold of migraine attacks, thereby increasing the risk of chronic migraine. Treatment options include oral medications, nerve blockade with local anaesthetics or corticoids, and neuromodulation. Well-defined diagnostic criteria are crucial for the identification of chronic migraine. The International Headache Society classification of chronic migraine was recently updated, and now allows co-diagnosis of chronic migraine and medication overuse headache. This Review provides an up-to-date overview of the classification of chronic migraine, basic mechanisms and risk factors of migraine chronification, and the currently established treatment options. PMID- 27389095 TI - Relaxant Effects of the Selective Estrogen Receptor Modulator, Bazedoxifene, and Estrogen Receptor Agonists in Isolated Rabbit Basilar Artery. AB - We have previously shown that the selective estrogen receptor modulator, bazedoxifene, improves the consequences of ischemic stroke. Now we aimed to characterize the effects and mechanisms of action of bazedoxifene in cerebral arteries. Male rabbit isolated basilar arteries were used for isometric tension recording and quantitative polymerase chain reaction. Bazedoxifene relaxed cerebral arteries, as 17-beta-estradiol, 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5 triyl)trisphenol [estrogen receptor (ER) alpha agonist], and G1 [G protein coupled ER (GPER) agonist] did it (4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5 triyl)trisphenol > bazedoxifene = G1 > 17-beta-estradiol). 2,3-Bis(4 hydroxyphenyl)-propionitrile (ERbeta agonist) had no effect. Expression profile of genes encoding for ERalpha (ESR1), ERbeta (ESR2), and GPER was GPER > ESR1 > ESR2. As to the endothelial mechanisms, endothelium removal, N-nitro-L-arginine methyl ester, and indomethacin, did not modify the relaxant responses to bazedoxifene. As to the K channels, both a high-K medium and the Kv blocker, 4 aminopyridine, inhibited the bazedoxifene-induced relaxations, whereas tetraethylammonium (nonselective K channel blocker), glibenclamide (selective KATP blocker) or iberiotoxin (selective KCa blocker) were without effect. Bazedoxifene also inhibited both Ca- and Bay K8644-elicited contractions. Therefore, bazedoxifene induces endothelium-independent relaxations of cerebral arteries through (1) activation of GPER and ERalpha receptors; (2) increase of K conductance through Kv channels; and (3) inhibition of Ca entry through L-type Ca channels. Such a profile is compatible with the beneficial effects of estrogenic compounds (eg, SERMs) on vascular function and, specifically, that concerning the brain. Therefore, bazedoxifene could be useful in the treatment of cerebral disorders in which the cerebrovascular function is compromised (eg, stroke). PMID- 27389096 TI - Structural Studies on the Extracellular Domain of Sensor Histidine Kinase YycG from Staphylococcus aureus and Its Functional Implications. AB - Bacterial two-component signal transduction systems are used to adapt to fluctuations in the environment. YycG, a key two-component histidine kinase in Staphylococcus aureus, plays an essential role in cell viability and regulates cell wall metabolism, biofilm formation, virulence, and antibiotic resistance. For these reasons, YycG is considered a compelling target for the development of novel antibiotics. However, to date, the signaling mechanism of YycG and its stimulus are poorly understood mainly because of a lack of structural information on YycG. To address this deficiency, we determined the crystal structure of the extracellular domain of S. aureus YycG (YycGex) at 2.0-A resolution. The crystal structure indicated two subunits with an extracellular Per-Arnt-Sim (PAS) topology packed into a dimer with interloop interactions. Disulfide scanning using cysteine-substituted mutants revealed that YycGex possessed dimeric interfaces not only in the loop but also in the helix alpha1. Cross-linking studies using intact YycG demonstrated that it was capable of forming high molecular weight oligomers on the cell membrane. Furthermore, we also observed that two auxiliary proteins of YycG, YycH and YycI, cooperatively interfered with the multimerization of YycG. From these results, we propose that signaling through YycG is regulated by multimerization and binding of YycH and YycI. These structural studies, combined with biochemical analyses, provide a better understanding of the signaling mechanism of YycG, which is necessary for developing novel antibacterial drugs targeting S. aureus. PMID- 27389098 TI - Comparative Composition of Brown Rice Lipids (Lipid Fractions) of Indica and Japonica Rices. AB - The brown rice lipids were analyzed from three japonica and two indica rices. They had substantially no difference in the ratio of NL, GL, and PL, the C16/C18 (16:0/the sum of 18:0, 18:1, 18:2, and 18:3) ratio in PL classes, and in the order of unsaturated index in each glycerolipid class among the five varieties. However, the chemical compositions of glyceroglycolipids and cerebroside were different in indica and japonica rices. The contents of 18:3 of MGDG and DGDG were higher in japonica than indica rices, but those of 16:0 were reversed. The ratio of C14-20/C21-26 of the hydroxy fatty acids in cerebroside was 1.18 in japonica and 0.62 in indica rices. Furthermore, the ratio of the trihydroxy sphingoid bases to dihydroxy ones showed a great difference between the subspecies. Unsaturated fatty acid contents in the TG and PL classes were largely different from each other among japonica rices harvested in separate districts. PMID- 27389099 TI - Effective Moisture Diffusivity of Fresh Japanese Noodle (udon) as a Function of Temperature. AB - The effect of moisture content and temperature on the effective moisture diffusivity was investigated to identify the optimal drying condition for Japanese noodle (udon) by using a diffusion model. The drying of fresh udon with different moisture contents was carried out under constant conditions of relative humidity and airflow at 20 degrees C, 30 degrees C and 40 degrees C. The effective moisture diffusivity calculated from diffusion model was found to be constant at each temperature, and not to be influenced by the initial moisture content of the fresh udon. The moisture content calculated from the effective moisture diffusivity (2.1-3.7*10(-7) cm(2) s(-1)) agrees well with the experimental data. The effect of temperature on the effective moisture diffusivity was adequately modeled by the Arrhenius relationship. The activation energy was 21.3 kJ mol(-1). PMID- 27389097 TI - Biodiversity and Activity of the Gut Microbiota across the Life History of the Insect Herbivore Spodoptera littoralis. AB - Microbes that live inside insects play critical roles in host nutrition, physiology, and behavior. Although Lepidoptera (butterflies and moths) are one of the most diverse insect taxa, their microbial symbionts are little-studied, particularly during metamorphosis. Here, using ribosomal tag pyrosequencing of DNA and RNA, we investigated biodiversity and activity of gut microbiotas across the holometabolous life cycle of Spodoptera littoralis, a notorious agricultural pest worldwide. Proteobacteria and Firmicutes dominate but undergo a structural "metamorphosis" in tandem with its host. Enterococcus, Pantoea and Citrobacter were abundant and active in early-instar, while Clostridia increased in late instar. Interestingly, only enterococci persisted through metamorphosis. Female adults harbored high proportions of Enterococcus, Klebsiella and Pantoea, whereas males largely shifted to Klebsiella. Comparative functional analysis with PICRUSt indicated that early-instar larval microbiome was more enriched for genes involved in cell motility and carbohydrate metabolism, whereas in late-instar amino acid, cofactor and vitamin metabolism increased. Genes involved in energy and nucleotide metabolism were abundant in pupae. Female adult microbiome was enriched for genes relevant to energy metabolism, while an increase in the replication and repair pathway was observed in male. Understanding the metabolic activity of these herbivore-associated microbial symbionts may assist the development of novel pest-management strategies. PMID- 27389100 TI - Complete Growth Inhibition of Bacillus subtilis by Nisin-Producing Lactococci in Fermented Soybeans. AB - The growth inhibition by nisin-producing lactococci against Bacillus subtilis and its application to soybean miso fermentation were investigated. Lactococcus lactis subsp. lactis IFO12007 (nisin-producing, salt-intolerant) rapidly proliferated to more than 10(9) cells/g in cooked soybeans without any excessive pH decrease. In spite of the mild decrease in pH, the growth of B. subtilis was completely inhibited; no living cells were detected in a soybean sample inoculated with 10(6) cells/g and incubated for 24 to 72 h. This Lc. lactis was applied to soybean miso fermentation as a starter culture. It produced high nisin activity (1.28*10(5) AU/g) in cooked soybean, resulting in the complete growth inhibition of B. subtilis, which had been inoculated at the beginning of the koji fermentation, throughout the process of miso production. Over-acidification, which is undesirable for miso quality, was successfully prevented simply by adding salt which killed the salt-intolerant Lc. lactis. Furthermore, the nisin activity in miso disappeared with aging. PMID- 27389101 TI - Kinetic Analysis of the Autoxidation of Ethyl Eicosapentaenoate at Different Oxygen Levels. AB - The autoxidation of such n-3 polyunsaturated fatty acid (PUFA) ethyl esters as ethyl eicosapentaenoate and ethyl docosahexaenoate was investigated at various temperatures. Extensive studies of the oxidative reaction for ethyl eicosapentaenoate were carried out at different oxygen levels. At the same oxygen level and temperature, the autocatalytic reaction rate, by which oxidation progressed in the first half period, was about 1.5-2.5 times larger than the first-order reaction rate which governed the oxidation in the second half period. The reaction rate constants for ethyl eicosapentaenoate at different oxygen levels correlated well with the Langmuir-type equation of the oxygen concentration, in which the Langmuir parameter was independent of temperature. PMID- 27389102 TI - Recovery of Caco-2 Cell Monolayers to Normal from the Transport-enhanced State Induced by Capric Acid Sodium Salt and its Monoacylglycerol. AB - Caco-2 cell monolayers were used as a model of the intestinal epithelium to investigate the recovery profile from the transport-enhanced state induced by the transport enhancers, capric acid sodium salt (C10FANa) and capric acid monoacylglycerol (C10MG). The transepithelial electrical resistance, MTT (3-(4,5 dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) assay, and lactate dehydrogenase (LDH) release rate were investigated. The cell monolayer recovered depending on the concentration of the enhancer and on the exposure time. The MTT assay revealed that the cells recovered their mitochondrial dehydrogenase activity without proliferation. The cell monolayer exposed to C10FANa released LDH to both the apical and basolateral sides, but to C10MG, only to the apical side. The results were compared with those for SDS and taurocholic acid sodium salt, and the effect of C10FANa was found to be different. These results suggest that the damage by MCFA compounds is recoverable and that the recovery can be assessed by an MTT assay, but that the LDH-release behavior is different among the enhancers. PMID- 27389103 TI - An Isoelectric Separation of Soybean beta-Amylase Isoforms and Their Enzymic Characteristics. AB - Authentic soybean beta-amylase preparation, purified to homogeneity as judged by SDS-PAGE by using an affinity purification step, was composed of four pI differing isoforms. By chromatofocusing, these isoforms were separated into three fractions, designated as fractions 1-3 in the order of elution. Fraction 1 contained two isoforms having the same molecular mass (55,989 Da), as measured by mass spectrometric analysis, with different pIs, 5.32 (Isoform I) and 5.22 (Isoform II). Fraction 2 showed a single isoform having a molecular mass of 55,994 Da and having a pI of 5.09. This component, named Isoform III, existed rather in excess in a mixture of the authentic enzyme isoforms. The remainder (fraction 3) also contained a single component (Isoform IV) which has a molecular mass of 56,310 Da with a pI of 4.97. Chemical analyses indicated that the N termini and the C-terminal tripeptides of four pI-separated isoforms mentioned are similar to one another, and are blocked and are NH2-Val-Asp-Gly-COOH, respectively. Moreover, enzymic properties involving specific activity and the value of kcat/Km for the above three fractions are almost the same, and also agreed completely with those of an unfractionated authentic beta-amylase preparation. PMID- 27389104 TI - Synthesis of 4'-C-Ethynyl-beta-D-ribo-pentofuranosyl Pyrimidines. AB - The 4'-C-ethynyl-beta-D-ribo-pentofuranosylpyrimidines were prepared from D glucose through properly protected 4'-C-formyl-D-ribo-ribofuranose as the key intermediate, and preliminary biological tests against some viruses and tumor cells showed that the compounds were not active. PMID- 27389105 TI - Insecticidal Activity of alpha-Methylene-gamma-butyrolactone against Several Insect Pests. AB - alpha-Methylene-gamma-butyrolactone (tulipalin A), which has been found to possess effective insecticidal activity against Thrips palmi (Thysanoptera; Thripinae), was examined on several insect pests. This compound caused high mortality against thrips species such as Frankliniella occidentallis and Frankliniella intonsa. In addition, some mortality was observed against other agricultural pest species. It is considered that alpha-methylene-gamma butyrolactone has a wide spectrum of insecticidal activity. PMID- 27389106 TI - Simultaneous Determination of Different Classes of Lipid Hydroperoxides by High Performance Liquid Chromatography with Post Column Detection by a Ferrous/Xylenol Orange Reagent. AB - A novel high-performance liquid chromatographic (HPLC) method with post-column detection was developed to simultaneously analyze the lipid hydroperoxides of polar and nonpolar lipids. The HPLC method uses a reversed-phase column (octyl bonded silica) and a mobile phase of water/acetonitrile/methanol. Hydroperoxides were detected at 592 nm by using a ferrous (II)/xylenol orange (FeXO) reagent. This method enabled the separation of fatty acid hydroperoxides, phosphatidylcholine hydroperoxides, and hydroperoxides of neutral lipids, including triacylglycerol hydroperoxides and cholesterol ester hydroperoxides, by chromatography. These hydroperoxides could be quantified in a range between 40 pmol and 2 nmol. This new method was applied to estimate the lipid hydroperoxides formed during the photosensitized oxidation of rat plasma. PMID- 27389107 TI - Errata. AB - Fig. 1 The relative cinfiguration for compound 5 is incorrect. Please replace with the structure provided below. PMID- 27389108 TI - Double-layer-gate architecture for few-hole GaAs quantum dots. AB - We report the fabrication of single and double hole quantum dots using a double layer-gate design on an undoped accumulation mode [Formula: see text]/GaAs heterostructure. Electrical transport measurements of a single quantum dot show varying addition energies and clear excited states. In addition, the two-level gate architecture can also be configured into a double quantum dot with tunable inter-dot coupling. PMID- 27389110 TI - Mode of Delivery to the Brave New (Microbial) World: A Defining Moment for the Respiratory Microbiome? PMID- 27389109 TI - Tyrosine-sulfated V2 peptides inhibit HIV-1 infection via coreceptor mimicry. AB - Tyrosine sulfation is a post-translational modification that facilitates protein protein interaction. Two sulfated tyrosines (Tys173 and Tys177) were recently identified within the second variable (V2) loop of the major HIV-1 envelope glycoprotein, gp120, and shown to contribute to stabilizing the intramolecular interaction between V2 and the third variable (V3) loop. Here, we report that tyrosine-sulfated peptides derived from V2 act as structural and functional mimics of the CCR5 N-terminus and potently block HIV-1 infection. Nuclear magnetic and surface plasmon resonance analyses indicate that a tyrosine-sulfated V2 peptide (pV2alpha-Tys) adopts a CCR5-like helical conformation and directly interacts with gp120 in a CD4-dependent fashion, competing with a CCR5 N-terminal peptide. Sulfated V2 mimics, but not their non-sulfated counterparts, inhibit HIV 1 entry and fusion by preventing coreceptor utilization, with the highly conserved C-terminal sulfotyrosine, Tys177, playing a dominant role. Unlike CCR5 N-terminal peptides, V2 mimics inhibit a broad range of HIV-1 strains irrespective of their coreceptor tropism, highlighting the overall structural conservation of the coreceptor-binding site in gp120. These results document the use of receptor mimicry by a retrovirus to occlude a key neutralization target site and provide leads for the design of therapeutic strategies against HIV-1. PMID- 27389111 TI - Assessment of the dietary intake of propylene glycol in the Korean population. AB - An improved method for the analysis of propylene glycol (PG) in foods using a gas chromatography-flame ionisation detector (GC-FID), with confirmation by GC-MS, was validated by measuring several analytical parameters. The PG concentrations in 1073 products available in Korean markets were determined. PG was detected in 74.1% of the samples, in a concentration range from the limit of detection (n.d., 0.39 MUg ml(-1)) to 12,819.9 mg kg(-1). The Korea National Health and Nutrition Examination Survey (KNHANES) 2011-2013 reported the mean intake levels of PG from all sources by the general population and consumers were 26.3 mg day(-1) (0.52 mg kg(-1) day(-1)) and 34.3 mg day(-1) (0.67 mg kg(-1) day(-1)), respectively. The 95th percentile intake levels of the general population and consumers were 123.6 mg day(-1) (2.39 mg kg(-1) day(-1)) and 146.3 mg day(-1) (2.86 mg kg(-1) day( 1)), respectively. In all groups of the general population, breads were the main contributors to the total PG intake. These reports provide a current perspective on the daily intake of PG in the Korean population. PMID- 27389112 TI - A Preliminary Survey Examining Predictors of Burnout in Pain Medicine Physicians in the United States. AB - BACKGROUND: Burnout is a prolonged response to chronic emotional and interpersonal stressors on the job, defined by 3 dimensions: exhaustion, depersonalization, and reduced personal accomplishment. While there is a growing body of research on burnout in physicians, there is a dearth of literature on burnout in pain medicine physicians. OBJECTIVE: This study aimed to determine the incidence of burnout amongst pain medicine physicians and whether there are sociodemographic or psychological demand characteristics of the job setting that predict burnout in pain medicine physicians. STUDY DESIGN AND SETTING: Cross section survey of pain medicine physicians across the United States. METHODS: Pain medicine physicians were asked questions on sociodemographics and professional characteristics and measures of decisional authority, psychological job demands, job insecurity, perceived coworker support, and job dissatisfaction. RESULTS: Two hundred seven pain medicine physicians' responses were analyzed, 60.4% reported high emotional exhaustion, 35.7% reported high depersonalization, and 19.3% reported low personal accomplishment. Greater psychological job demands and greater job dissatisfaction predicted greater emotional exhaustion. Younger age and greater job dissatisfaction predicted higher depersonalization. Lastly, lower coworker support and greater job dissatisfaction predicted lower personal accomplishment. There were no statistical violations of assumptions or collinearity. LIMITATIONS: Low response rate and potential for response bias limit generalizability of the study. CONCLUSION(S): Pain medicine physicians in the United States reported high levels of emotional exhaustion, often considered the most taxing aspect of burnout. Job dissatisfaction appeared to be the leading agent in the development of all 3 components of burnout in pain medicine physicians in the United States. PMID- 27389113 TI - Is Genicular Nerve Radiofrequency Ablation Safe? A Literature Review and Anatomical Study. AB - Genicular nerve radiofrequency ablation (RFA) has recently gained popularity as an intervention for chronic knee pain in patients who have failed other conservative or surgical treatments. Long-term efficacy and adverse events are still largely unknown. Under fluoroscopic guidance, thermal RFA targets the lateral superior, medial superior, and medial inferior genicular nerves, which run in close proximity to the genicular arteries that play a crucial role in supplying the distal femur, knee joint, meniscus, and patella. RFA targets nerves by relying on bony landmarks, but fails to provide visualization of vascular structures. Although vascular injuries after genicular nerve RFA have not been reported, genicular vascular complications are well documented in the surgical literature. This article describes the anatomy, including detailed cadaveric dissections and schematic drawings, of the genicular neurovascular bundle. The present investigation also included a comprehensive literature review of genicular vascular injuries involving those arteries which lie near the targets of genicular nerve RFA. These adverse vascular events are documented in the literature as case reports. Of the 27 cases analyzed, 25.9% (7/27) involved the lateral superior genicular artery, 40.7% (11/27) involved the medial superior genicular artery, and 33.3% (9/27) involved the medial inferior genicular artery. Most often, these vascular injuries result in the formation of pseudoaneurysm, arteriovenous fistula (AVF), hemarthrosis, and/or osteonecrosis of the patella. Although rare, these complications carry significant morbidities. Based on the detailed dissections and review of the literature, our investigation suggests that vascular injury is a possible risk of genicular RFA. Lastly, recommendations are offered to minimize potential iatrogenic complications. PMID- 27389114 TI - Auto-Targeted Neurostimulation Is Not Superior to Placebo in Chronic Low Back Pain: A Fourfold Blind Randomized Clinical Trial. AB - BACKGROUND: Myofascial trigger points (MTrPs) are common in people with musculoskeletal pain and may play a role in chronic nonspecific low back pain (CLBP). One of the potential treatments of MTrPs is the Nervomatrix Soleve(r) auto-targeted neurostimulation device, providing targeted transcutaneous electrical nerve stimulation (TENS) to MTrPs in the lower back muscles. To date, no controlled studies have evaluated the effectiveness of this device for the pain management of this population. OBJECTIVE: To examine whether the Nervomatrix Soleve(r) auto-targeted neurostimulation device is superior over placebo for the treatment of CLBP. STUDY DESIGN: A fourfold-blind randomized controlled trial was conducted. SETTING: Brussels University Hospital, health care centers and pharmacies around Belgium. METHODS: Participants with CLBP for at least 3 months were randomly assigned to the experimental (the Nervomatrix Soleve(r) auto targeted neurostimulation device providing TENS-stimulation and mechanical pressure) or placebo group (the Nervomatrix Soleve(r) auto-targeted neurostimulation device providing mechanical pressure alone without current). The treatment protocol in both groups consisted of 6 treatment sessions per patient. Participants were evaluated at baseline prior to the intervention, immediately following treatment, and at one month follow-up. Pain and pain behavior (steps climbed) were assessed as primary outcome measures. Secondary outcome measures were pain functioning, health beliefs, symptoms of central sensitization, pain catastrophizing, and kinesiophobia. RESULTS: In total, 39 participants were included in the study. Participants in both groups improved significantly for pain and functioning, but no significant differences were observed between groups. These improvements were not clinically meaningful for any of the reported measures. The health beliefs changed significantly in both groups (P < 0.05), with superior results at follow-up in the placebo group. LIMITATIONS: The follow up period is limited to one month. CONCLUSIONS: Treatment of MTrPs with the Nervomatrix Soleve(r) auto-targeted neurostimulation device in patients with CLBP does not result in a better outcome than placebo-treatment in terms of pain, pain behavior, functioning, central sensitization, pain catastrophizing, and health beliefs. PMID- 27389115 TI - Bipolar High-Voltage, Long-Duration Pulsed Radiofrequency Improves Pain Relief in Postherpetic Neuralgia. AB - BACKGROUND: Postherpetic neuralgia (PHN) is often refractory to existing treatments. Treatment of the dorsal root ganglion (DRG) using monopolar pulsed radiofrequency (PRF), which is a non- or minimally neurodestructive technique, is not efficacious in all patients. OBJECTIVES: This study aimed to determine the safety and clinical efficacy of bipolar high-voltage, long-duration PRF on the DRG in PHN patients. STUDY DESIGN: Self before-after controlled clinical trial. SETTING: Department of Pain Medicine, the First Affiliated Hospital of China Medical University. METHODS: Ninety patients diagnosed with PHN for > 3months were included. Bipolar high-voltage, long-duration PRF at 42 degrees C for 900 seconds was applied after the induction of paresthesias covered the regions of hyperalgesic skin. The therapeutic effects were evaluated using a visual analog scale (VAS) and the 36-item Short Form health survey (SF-36) before treatment and one, 4, 8, and 12 weeks after PRF. RESULTS: The VAS scores at one, 4, 8, and 12 weeks after PRF treatment were significantly lower than before treatment (P < 0.001). The SF-36 scores, which included physical functioning, physical role, bodily pain, general health perceptions, vitality, social function, emotional role, and the mental health index, were significantly improved up to 12 weeks after PRF treatment (P < 0.001). No serious adverse effects were identified following treatment. The main adverse reactions included pain, tachycardia, and high blood pressure (especially when the field strength was enhanced). LIMITATIONS: Single center study, relatively small number of patients, lack of a control group. CONCLUSION: Bipolar high-voltage, long-duration PRF on the DRG is an effective and safe therapeutic alternative for PHN patients. This treatment could improve the quality of life of PHN patients. CLINICAL TRIAL REGISTRATION: NO ChiCTR-OCS-14005461. PMID- 27389117 TI - Percutaneous Vertebroplasty versus Conservative Treatment for One Level Thoracolumbar Osteoporotic Compression Fracture: Results of an Over 2-Year Follow up. AB - We retrospectively compared the clinical and radiological results of percutaneous vertebroplasty with those of conservative treatment in the management of thoracolumbar osteoporotic compression fractures. Sixty-five patients who could be followed up for more than 2 years with thoracic and lumbar spine osteoporotic compression fractures, between January 2005 and October 2010, were reviewed. The patients were divided into 2 groups according to the type of management: group 1, non-operated group treated conservatively; group 2, operated group that underwent percutaneous vertebroplasty. We assessed the clinical and radiological changes at postoperative and follow-up periods in both groups.The male-to-female ratio and mean age of the patients were 11:54 and 73.04 years (range, 50 - 90 years), respectively. The location and number of treated vertebrae were as follows: T4 = 1, T6 = 1, T7 = 3, T8 = 1, T9 = 2, T10 = 1, T11 = 8, T12 = 11, L1 = 17, L2 = 10, L3 = 6, L4 = 3, and L5 = 1. The mean T-score was -3.37. The overall VAS score and the VAS score until 6 months post-injury were statistically more improved in group 2 than in group 1 (P < 0.05 and P < 0.005, respectively). Overall, the compression ratio was statistically more improved in group 2 than in group 1 (P < 0.05).Early pain control and restoration of the compressed vertebral body are the beneficial and real effects of percutaneous vertebroplasty in patients with thoracolumbar osteoporotic compression fractures. PMID- 27389116 TI - Predictive Factors of Chronic Post-Surgical Pain at 6 Months Following Knee Replacement: Influence of Postoperative Pain Trajectory and Genetics. AB - BACKGROUND: The frequency of chronic postsurgical pain (CPSP) after knee replacement remains high, but might be decreased by improvements to prevention. OBJECTIVES: To identify pre- and postsurgical factors predictive of CPSP 6 months after knee replacement. STUDY DESIGN: Single-center prospective observational study. SETTING: An orthopedic unit in a French hospital. METHODS: Consecutive patients referred for total or unicompartmental knee arthroplasty from March to July 2013 were prospectively invited to participate in this study. For each patient, we recorded preoperative pain intensity, anxiety and depression levels, and sensitivity and pain thresholds in response to an electrical stimulus. We analyzed OPRM1 and COMT single-nucleotide polymorphisms. Acute postoperative pain (APOP) in the first 5 days after surgery was modeled by a pain trajectory. Changes in the characteristics and consequences of the pain were monitored 3 and 6 months after surgery. Bivariate analysis and multivariate logistic regression were conducted to identify predictors of CPSP. RESULTS: We prospectively evaluated 104 patients in this study, 74 (28.8%) of whom reported CPSP at 6 months. Three preoperative factors were found to be associated with the presence of CPSP in multivariate logistic regression analysis: high school diploma level (OR = 3.83 [1.20 - 12.20]), consequences of pain in terms of walking ability, as assessed with the Brief Pain Inventory short form "walk" item (OR = 4.06 [1.18 - 13.94]), and a lack of physical activity in adulthood (OR = 4.01 [1.33 - 12.10]). One postoperative factor was associated with the presence of CPSP: a high intensity APOP trajectory. An association of borderline statistical significance was found with the A allele of the COMT gene (OR = 3.4 [0.93 - 12.51]). Two groups of patients were identified on the basis of their APOP trajectory: high (n = 28, 26%) or low (n = 80, 74%) intensity. Patients with high-intensity APOP trajectory had higher anxiety levels and were less able to walk before surgery (P < 0.05). LIMITATIONS: This was a single-center study and the sample may have been too small for the detection of some factors predictive of CPSP or to highlight the role of genetic factors. CONCLUSION: Our findings suggest that several preoperative and postoperative characteristics could be used to facilitate the identification of patients at high risk of CPSP after knee surgery. All therapeutic strategies decreasing APOP, such as anxiety management or performing knee replacement before the pain has a serious effect on ability to walk, may help to decrease the risk of CPSP. Further prospective studies testing specific management practices, including a training program before surgery, are required. PMID- 27389118 TI - Ultrasound-Guided Genicular Nerve Pulsed Radiofrequency Treatment For Painful Knee Osteoarthritis: A Preliminary Report. AB - BACKGROUND: Genicular nerve ablation with radiofrequency (RF) has recently emerged as a promising treatment in the management of osteoarthritis related knee pain. To date, genicular nerve injections have been performed under fluoroscopic guidance. OBJECTIVE: To evaluate the effect of ultrasound-guided genicular nerve pulsed RF treatment on chronic knee pain and function in patients with knee osteoarthritis. STUDY DESIGN: Single-arm prospective study. SETTING: University hospital and rehabilitation center in Turkey. METHODS: A review was made of 29 patients with medial knee osteoarthritis who had undergone genicular nerve block in the previous 6 months. Patients with at least 50% reduction in the visual analog scale (VAS) score after genicular nerve block and with no on-going pain relief were selected for the study. Ultrasound-guided genicular nerve pulsed RF was applied to 15 knees of 9 patients. Pain and knee function were assessed with 100-mm VAS and Western Ontario and McMaster Universities (WOMAC) index throughout 3 months. RESULTS: A significant reduction in VAS scores was detected over time after the pulsed RF procedure (f: 69.24, P < 0.01). There was a significant improvement in the WOMAC scores (f: 539.68 , P < 0.01). LIMITATIONS: The small number of participants, the lack of a control group, and short follow-up period were limitations of the study. CONCLUSIONS: Genicular nerve pulsed RF treatment has been found to be safe and beneficial in osteoarthritis related knee pain. Further studies with a larger population and randomized controlled study design are warranted to confirm the positive findings of this preliminary report. PMID- 27389119 TI - A Multicenter Clinical Study on Treating Post-Dural Puncture Headache with an Intravenous Injection of Aminophylline. AB - BACKGROUND: Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture. Aminophylline has been reported to be effective in the prevention of PDPH in some clinical studies, but its efficacy for the treatment of PDPH has been unproven. OBJECTIVE: To evaluate the efficacy and safety of an intravenous (IV) injection of aminophylline on PDPH. STUDY DESIGN: The study was a multicenter, open-label study to assess the effectiveness and safety of aminophylline on PDPH. SETTING: The First Affiliated Hospital of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, and Henan Province Hospital of Traditional Chinese Medicine. METHODS: Thirty-two PDPH patients received an IV injection of aminophylline. The primary and secondary endpoints were the degree of headache and the patient's overall response to the treatment, respectively. Treatment safety was evaluated based on the occurrence of adverse reactions. RESULTS: Thirty-one patients completed the study. Before the initial aminophylline administration, the visual analog scale (VAS) score was 7.72 +/- 1.65. The VAS scores at 30 minutes, one hour, 8 hours, one day, and 2 days post-treatment were 4.84 +/- 2.53, 3.53 +/- 2.06, 2.38 +/- 1.96, 1.44 +/- 1.87, and 0.81 +/- 1.79, respectively, and were statistically significantly different (P < 0.05) compared with those before treatment. More than 50% (17/32) of the patients reported that they were "very much improved" or "much improved" 30 minutes after the initial treatment, increasing to 93.8% (30/32) at 2 days post-treatment. One patient experienced mild allergic reaction after treatment. LIMITATIONS: Although this study had the largest sample size among current studies on treating PDPH with theophylline drugs, the sample size was still relatively small and the method employed was not compared with a placebo or other current clinical treatments for PDPH. CONCLUSION: An IV injection of aminophylline may be an effective and safe early-stage treatment for PDPH. PMID- 27389120 TI - CT-Guided Percutaneous Femoroplasty (PFP) for the Treatment of Proximal Femoral Metastases. AB - BACKGROUND: The spine, pelvis, skull, and femur are the most common sites of bone metastases, and pain is the main symptom of metastatic tumors. Percutaneous femoroplasty (PFP) is becoming increasingly popular for treating proximal femoral metastases. OBJECTIVES: To assess the clinical value and feasibility of PFP performed under the guidance of computed tomography (CT). STUDY DESIGN: A retrospective clinical review comparing pain intensity and the ability to perform activities of daily living before and after treatment with PFP. SETTING: Single academic medical center. METHODS: Sixteen patients with proximal femoral metastasis were treated with PFP under CT guidance and followed up for 6 - 12 months. Pain intensity was evaluated using the visual analog scale (VAS) and patients' quality of life was evaluated using the Barthel Index of Activities of Daily Living (BIADL) preoperatively and at both 7 days and 6 months after PFP. RESULTS: The mean VAS score decreased from 7.44 +/- 0.81 preoperatively to 2.69 +/- 0.79 at 7 days postoperatively and 1.25 +/- 0.93 at 6 months postoperatively. The BIADL score increased from 44.06 +/- 9.53 preoperatively to 69.06 +/- 8.61 at 7 days postoperatively and 83.13 +/- 6.55 at 6 months postoperatively. No patients suffered from pulmonary embolism or complications such as pathologic fracture of the proximal femur. The median overall survival was 12 months. One patient experienced cement leakage into the hip, and the injection was immediately stopped. Then dexamethasone was injected intravenously to prevent potential pulmonary fat embolism caused by localized high pressure. LIMITATIONS: The study evaluated a single group of patients before and after CT-guided PFP and did not include a comparison with conventional fluoroscopic approaches in a large patient sample. CONCLUSION: Use of CT-guided PFP was associated with a low risk of complications and improvement in patients' quality of life. CT guidance made the operation easy and safe, and thus, this approach represents a potential treatment option for proximal femoral metastases if indications are observed closely. PMID- 27389121 TI - High-Resolution Three-Dimensional Computed Tomography for Assessing Complications Related to Intrathecal Drug Delivery. AB - BACKGROUND: The assessment of the functionality of intrathecal drug delivery (IDD) systems remains difficult and time-consuming. Catheter-related problems are still very common, and sometimes difficult to diagnose. OBJECTIVES: The aim of the present study is to investigate the accuracy of high-resolution three dimensional computed tomography (CT) in order to detect catheter-related pump dysfunction. STUDY DESIGN: An observational, retrospective investigation. SETTING: Academic medical center in Germany. METHODS: We used high-resolution three dimensional (3D) computed tomography with volume rendering technique (VRT) or fluoroscopy and conventional axial-CT to assess IDD-related complications in 51 patients from our institution who had IDD systems implanted for the treatment of chronic pain or spasticity. RESULTS: Twelve patients (23.5%) presented a total of 22 complications. The main type of complication in our series was catheter related (50%), followed by pump failure, infection, and inappropriate refilling. Fluoroscopy and conventional CT were used in 12 cases. High-resolution 3D CT VRT scan was used in 35 instances with suspected yet unclear complications. Using 3D CT (VRT) the sensitivity was 58.93% - 100% (CI 95%) and the specificity 87.54% - 100% (CI 95%).The positive predictive value was 58.93% - 100% (CI 95%) and the negative predictive value: 87.54% - 100% (CI 95%).Fluoroscopy and axial CT as a combined diagnostic tool had a sensitivity of 8.3% - 91.7% (CI 95%) and a specificity of 62.9% - 100% (CI 95%). The positive predictive value was 19.29% - 100% (CI 95%) and the negative predictive value: 44.43% - 96.89% (CI 95%). LIMITATIONS: This study is limited by its observational design and the small number of cases. CONCLUSION: High-resolution 3D CT VRT is a non- invasive method that can identify IDD-related complications with more precision than axial CT and fluoroscopy. PMID- 27389122 TI - Functional Reorganization of the Primary Somatosensory Cortex of a Phantom Limb Pain Patient. AB - Functional reorganization of the somatosensory system was widely observed in phantom limb pain patients. Whereas some studies demonstrated that the primary somatosensory cortex (S1) of the amputated limb was engaged with the regions around it, others showed that phantom limb pain was associated with preserved structure and functional organization in the former brain region. However, according to the law of use and disuse, the sensitivity of S1 of the amputated limb to pain-related context should be enhanced due to the adaptation to the long lasting phantom limb pain experience. Here, we collected neurophysiological data from a patient with 21-year phantom limb pain using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) techniques. EEG data showed that both laser-evoked potentials (LEPs) and tactile-evoked potentials (TEPs) were clearly presented only when radiant-heat laser pulses and electrical pulses were delivered to the shoulder of the healthy limb, but not of the amputated limb. This observation suggested the functional deficit of somatosensory pathways at the amputated side. FMRI data showed that significant larger brain activations by painful rather than non-painful stimuli in video clips were observed not only at visual-related brain areas and anterior/mid-cingulate cortex, but also at S1 contralateral to the amputated limb. This observation suggested the increased sensitivity of S1 of the amputated limb to the pain-related context. In addition, such increase of sensitivity was significantly larger if the context was associated with the amputated limb of the patient. In summary, our findings provided novel evidence for a possible neuroplasticity of S1 of the amputated limb: in an amputee with long-lasting phantom limb pain, the sensitivity of S1 to pain-related and amputated-limb-related context was greatly enhanced. PMID- 27389123 TI - Finite Element Analysis of the Effect of Epidural Adhesions. AB - BACKGROUND: It is well documented that epidural adhesion is associated with spinal pain. However, the underlying mechanism of spinal pain generation by epidural adhesion has not yet been elucidated. OBJECTIVES: To elucidate the underlying mechanism of spinal pain generation by epidural adhesion using a two dimensional (2D) non-linear finite element (FE) analysis. STUDY DESIGN: A finite element analysis. SETTING: A two-dimensional nonlinear FE model of the herniated lumbar disc on L4/5 with epidural adhesion. METHODS: A two-dimensional nonlinear FE model of the lumbar spine was developed, consisting of intervertebral discs, dura, spinal nerve, and lamina. The annulus fibrosus and nucleus pulpous were modeled as hyperelastic using the Mooney-Rivlin equation. The FE mesh was generated and analyzed using Abaqus (ABAQUS 6.13.; Hibbitt, Karlsson & Sorenson, Inc., Providence, RI, USA). Epidural adhesion was simulated as rough contact, in which no slip occurred once two surfaces were in contact, between the dura mater and posterior annulus fibrosus. RESULTS: The FE model of adhesion showed significant stress concentration in the spinal nerves, especially on the dorsal root ganglion (DRG). The stress concentration was caused by the lack of adaptive displacement between the dura mater and posterior annulus fibrosus. The peak von Mises stress was higher in the epidural adhesion model (Adhesion, 0.67 vs. Control, 0.46). In the control model, adaptive displacement was observed with decreased stress in the spinal nerve and DRG (with adhesion, 2.59 vs. without adhesion, 3.58, P < 0.00). LIMITATIONS: This study used a 2D non-linear FE model, which simplifies the 3D nature of the human intervertebral disc. In addition, this 2D non-linear FE model has not yet been validated. CONCLUSION: The current study clearly demonstrated that epidural adhesion causes significantly increased stress in the spinal nerves, especially at the DRG. We believe that the increased stress on the spinal nerve might elicit more pain under similar magnitudes of lumbar disc protrusion. PMID- 27389125 TI - Multigene Pathway Engineering with Regulatory Linkers (M-PERL). AB - Multigene pathway engineering usually needs amounts of part libraries on transcriptional and translational regulation as well as mutant enzymes to achieve the optimal part combinations of the target pathways. We report a new strategy for multigene pathway engineering with regulatory linkers (M-PERL) focusing on tuning the transcriptional start site (TSS) of yeast promoters. The regulatory linkers are composed of two homologous ends of two adjacent gene parts for assembly and a central regulatory region between them. We investigated the effect of the homologous end's length on multigene assembly, analyzed the influences of truncated, replaced, and elongated TSS and the adjacent region on promoters, and introduced 5 to 40 random bases of N (A/T/C/G) in the central regulatory region of the linkers which effectively varied the promoter's strengths. The distinct libraries of five regulatory linkers were used simultaneously to assemble and tune all five genes in the violacein synthesis pathway. The gene expressions affected the product profiles significantly, and the recombinants for enhanced single component synthesis and varied composition synthesis were obtained. This study offers an efficient tool to assemble and regulate multigene pathways. PMID- 27389126 TI - Noninvasive hemoglobin measurement in pediatric trauma patients. AB - INTRODUCTION: Hemorrhage is a major cause of preventable death secondary to traumatic injury. Diagnosis often requires multiple blood draws, which are psychologically stressful in pediatric patients. The Pronto device is a pulse co oximeter that measures the total hemoglobin level using multiple wavelengths of light. The purpose of this study was to evaluate the accuracy of the noninvasive hemoglobin measurements relative to current invasive and point of care testing methods in pediatric trauma patients. METHODS: We performed a prospective observational trial involving patients younger than 17 years presenting to a Level I pediatric trauma center. Following admission, blood was sampled from each patient for testing using an i-Stat device (point-of-care hemoglobin) and a complete blood count within our core laboratory (invasive hemoglobin). Noninvasive hemoglobin analysis was performed within 15 minutes of phlebotomy. Data were evaluated using Spearman correlation and Bland-Altman analysis. RESULTS: Over 2 years, 114 patients had attempted noninvasive hemoglobin measurements, with a success rate of 89%. Mean +/- SD age was 9.2 +/- 5.1 years. Ninety percent of admissions were for blunt injury, 3% penetrating, 5% near drowning, and 1% burns. Mean invasive hemoglobin was 12.6 +/- 1.9 g/dL, mean point-of-care hemoglobin was 12.2 +/- 2.0 g/dL, and mean noninvasive hemoglobin was 12.3 +/- 1.6 g/dL. Noninvasive hemoglobin values were strongly correlated with both invasive and point of care measurements (R = 0.672 and R = 0.645, respectively; p < 0.001). Bland-Altman analysis comparing noninvasive to point-of care and invasive hemoglobin levels resulted in an estimated bias of -0.39 and 0.49, respectively. CONCLUSION: Noninvasive hemoglobin values had excellent correlation with both invasive and point-of-care hemoglobin measurements, although the device was not successful for all patients. Given the rapid availability of results and the lack of requirement of venipuncture, noninvasive hemoglobin monitoring may be a valuable adjunct in the initial evaluation and monitoring of pediatric trauma patients. LEVEL OF EVIDENCE: Diagnostic test study, level II. PMID- 27389127 TI - The diagnostic yield of commonly used investigations in pelvic gunshot wounds. AB - BACKGROUND: Patients who sustain pelvic gunshot wounds (GSWs) are at significant risk for injury owing to the density of pelvic structures. Currently, the optimal workup for pelvic GSWs is unclear. The aims of this study were to determine the diagnostic yield of tests commonly used in the investigation of pelvic GSWs and to develop a diagnostic algorithm. METHODS: All patients 15 years or older presenting to the Los Angeles County + University of Southern California Medical Center (January 2008 to February 2015) who sustained one or more pelvic GSWs were retrospectively identified. Patients' demographics, clinical assessment, investigations, procedures, and outcomes were abstracted. The diagnostic yield of computed tomographic (CT) scan, cystogram, gross inspection of the urine, urinalysis, endoscopy, and digital rectal examination (DRE) in the detection of clinically significant injuries to the pelvis were calculated. RESULTS: Three hundred seventy patients were included. Patients with peritonitis, hemodynamic instability, an unevaluable abdomen, or evisceration were taken to the operating room for immediate laparotomy (n = 138 [37.3%]). All others (n = 232 [62.7%]) underwent CT scan and further investigations as indicated. The sensitivity, specificity, positive predictive value, and negative predictive value of the investigations were CT scan: 1.00, 0.98, 0.74, and 1.00; cystogram: 1.00 for all parameters; gross inspection of the urine: 1.00 for all parameters; urinalysis: 1.00, 0.71, 0.17, and 1.00; endoscopy: 1.00, 0.82, 0.75, and 1.00; and DRE: 0.77, 0.99, 0.77, and 0.99. CONCLUSION: In the workup of pelvic GSWs, patients with hemodynamic instability, peritonitis, evisceration, or an unevaluable abdomen should undergo immediate laparotomy, while all others should undergo CT scan. Computed tomography-positive patients should be managed for their injuries. If the CT is negative, the likelihood of a clinically significant injury is very low. If the CT is equivocal for rectal or bladder injury, endoscopy or cystogram should be used to guide definitive management. There is no role for routine urinalysis or DRE. Further prospective validation of these findings is warranted. LEVEL OF EVIDENCE: Diagnostic study, level III; therapeutic study, level IV. PMID- 27389128 TI - Stress among surgical attending physicians and trainees: A quantitative assessment during trauma activation and emergency surgeries. AB - BACKGROUND: The adverse effects of stress on the wellness of trauma team members are well established; however, the level of stress has never been quantitatively assessed. The aim of our study was to assess the level of stress using subjective data and objective heart rate variability (HRV) among attending surgeons (ASs), junior residents (JRs) (PGY2/PGY3), and senior residents (SRs) (PGY5/PGY6) during trauma activation and emergency surgery. METHODS: We preformed a prospective study enrolling participants over eight 24-hour calls in our Level I trauma center. Stress was assessed based on decrease in HRV, which was recorded using body worn sensors. Stress was defined as HRV of less than 85% of baseline HRV. We collected subjective data on stress for each participant during calls. Three groups (ASs, JRs, SRs) were compared for duration of different stress levels through trauma activation and emergency surgery. RESULTS: A total of 22 participants (ASs: n = 8, JRs: n = 7, SRs: n = 7) were evaluated over 192 hours, which included 33 trauma activations and 50 emergency surgeries. Stress level increased during trauma activations and operations regardless of level of training. The ASs had significantly lower stress when compared with SRs and JRs during trauma activation (21.9 +/- 10.7 vs. 51.9 +/- 17.2 vs. 64.5 +/- 11.6; p < 0.001) and emergency surgery (30.8 +/- 7.0 vs. 53.33 +/- 6.9 vs. 56.1 +/- 3.8; p < 0.001). The level of stress was similar between JRs and SRs during trauma activation (p = 0.37) and emergency surgery (p = 0.19). There was no correlation between objectively measured stress level and subjectively measured stress using State-Trait Anxiety Inventory (R = 0.16; p = 0.01) among surgeons or residents. CONCLUSIONS: Surgeon wellness is a significant concern, and this study provides empirical evidence that trauma and acute care surgeons encounter mental strain and fail to recognize it. Stress management and burnout are very important in this high-intensity field, and this research may provide some insight in finding those practitioners who are at risk. LEVEL OF EVIDENCE: Epidemiologic study, level II. PMID- 27389129 TI - Bundles of care for resuscitation from hemorrhagic shock and severe brain injury in trauma patients-Translating knowledge into practice. PMID- 27389130 TI - Gender dimorphism in adipose tissue response to stress conditions: A plausible mechanism to explain the conflicting data regarding trauma and obesity. AB - INTRODUCTION: Obesity is a chronic low-grade inflammatory condition associated with the elaboration of proinflammatory cytokines and adipokines from adipose tissue. Gender dimorphism (in part due to sex hormones) has been identified after injury and hemorrhagic shock. We hypothesized that the sex hormones estrogen (E2) and testosterone (DHT) have disparate effects on inflammatory mediator production from adipose tissue under stress conditions. This was studied in an in vitro model. METHODS: Mature adipocytes differentiated from adipose-derived stem cells were cocultured (2:1) with macrophages (RAW 264.7) and subjected to hypoxia/reoxygenation (H/R) and/or incubation with physiologic (10 MUM) or stress (10 MUM) concentrations of epinephrine (epi). Estrogen or DHT was added in a range of physiologic concentrations, and culture supernatants were obtained 12 hours after incubation, and tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and adiponectin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Basal TNF-alpha and IL-6 release from cocultures was significantly increased in response to epi and/or H/R conditions. Estrogen decreased cytokine release to basal levels, whereas DHT had no effect. Of note, varying the concentration of epi had no effect on cytokine release. Basal levels of adiponectin release were significantly decreased in response to epi and/or H/R conditions. Estrogen exposure returned adiponectin levels to basal levels, whereas DHT had no effect. The inverse of this relationship was observed in regard to the sex hormones effect on leptin release. Estrogen returned leptin release to basal levels, whereas DHT had no effect. CONCLUSION: Stress levels of epi and H/R increased proinflammatory cytokine production and decreased adiponectin levels in adipocyte cocultures. Estrogen at physiologic concentrations decreased TNF-alpha, IL-6, and preserved adiponectin levels following epi and/or H/R conditions. There was no effect of DHT on mitigating the proinflammatory response. Our results suggest a gender dimorphism in adipose tissue under stress conditions that may explain the conflicting data in the literature. PMID- 27389131 TI - Presumptive antibiotic therapy for civilian trauma injuries. PMID- 27389132 TI - Magnitude of rib fracture displacement predicts opioid requirements. AB - INTRODUCTION: It is unknown whether the magnitude of rib fracture (RF) displacement predicts pain medication requirements in blunt chest trauma patients. METHODS: Adult blunt RF patients undergoing computed tomography (CT) of the chest admitted to an urban Level 1 trauma center (2007-2012) were retrospectively reviewed. Pain management in those with displaced RF (DRF), nondisplaced RF (NDRF), or combined DRF and NDRF (CRF) was compared by univariate analysis. Linear regression models were developed to determine whether total opioid requirements [expressed as log morphine equianalgesic dose (MED)] could be predicted by the magnitude of RF displacement (expressed as the sum of the Euclidean distance of all displaced RF) or number of RF, after adjusting for patient and injury characteristics. RESULTS: There were 245 patients, of whom 39 (16%) had DRF only, 77 (31%) had NDRF only, and 129 (53%) had CRF. Opioids were given to 224 patients (91%). Compared to DRF (mean, 1.7 RF per patient) and NDRF patients (2.4 RF per patient), those with CRF (6.8 RF per patient) were older and had more RF per patient and a higher Injury Severity Score (ISS) and MED (251 vs 53 and 105 mg, respectively, p < 0.0001 and p = 0.0045). They also more frequently received patient-controlled analgesia. Patients with displaced RF had a lower mean ISS and MED and received more epidural analgesia compared with patients with NDRF. Total MED was associated with both the magnitude of RF displacement (p < 0.0001) and the number of RF (p < 0.0001). Every 5-mm increase in total displacement predicted a 6.3% increase in mean MED (p = 0.0035), while every additional RF predicted an 11.2% increase in MED (p = 0.0001). These associations included adjustment for age, ISS, and presence of chest tubes. CONCLUSION: The magnitude of RF displacement and the number of RF predicted opioid requirements. This information may assist in anticipating patients with blunt RF who might have higher analgesic requirements. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 27389133 TI - Re: Hemorrhage control saves lives no matter the wounding pattern. PMID- 27389134 TI - Building on the Legacy of Dr. Basil A. Pruitt, Jr. at the U.S. Army Institute of Surgical Research During the Wars in Iraq and Afghanistan. PMID- 27389135 TI - Hemorrhage control saves lives no matter the wounding pattern. PMID- 27389136 TI - Penetrating cardiac injuries: A 36-year perspective at an urban, Level I trauma center. AB - BACKGROUND: This study evaluates patterns of injuries and outcomes from penetrating cardiac injuries (PCIs) at Grady Memorial Hospital, an urban, Level I trauma center in Atlanta, Georgia, over 36 years. METHODS: Patients sustaining PCIs were identified from the Trauma Registry of the American College of Surgeons and the Emory Department of Surgery database; data of patients who died prior to any therapy were excluded. Demographics and outcomes were compared over three time intervals: Period 1 (1975-1985; n = 113), Period 2 (1986-1996; n = 79), and Period 3 (2000-2010; n = 79). RESULTS: Two hundred seventy-one patients (86% were male; mean age, 33 years; initial base deficit = -11.3 mEq/L) sustained cardiac stab (SW, 60%) or gunshot wounds (GSW, 40%). Emergency department thoracotomy was performed in 67 (25%) of 271 patients. Overall mortality increased in the modern era (Period 1, 27%, vs. Period 2, 22%, vs. Period 3, 42%; p = 0.03) along with GSW mechanisms (Period 1, 32%, vs. Period 2, 33%, vs. Period 3, 57%; p = 0.001), GSW mortality (Period 1, 36%, vs. Period 2, 42%, vs. Period 3, 56%; p = 0.04), and multichamber injuries (Period 1, 12%, vs. Period 2, 10%, vs. Period 3, 34%; p< 0.001). In Period 3, GSWs (n = 45) resulted in multichamber injuries in 28 patients (62%) and multicavity injuries in 19 patients (42%). Surgeon-performed ultrasound accurately identified pericardial blood in 55 of 55 patients in Period 3. CONCLUSIONS: Increased frequency of GSWs in the past decade is associated with increased overall mortality, multichamber injuries, and multicavity injuries. Ultrasound is sensitive for detection of PCI. LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemioligc study, level III. PMID- 27389138 TI - DUI histories in intoxicated injured bicyclists. AB - INTRODUCTION: It has been well documented that the use of alcohol correlates with injury risk, especially in DUI (driving under the influence) and DWI (driving while intoxicated). Consumption of alcohol in patients presenting with bicycle related injuries is associated with greater injury severity, longer hospitalization, and higher health care costs. We hypothesized that intoxicated patients operating a bicycle with traumatic injuries have previous DUI or DWI convictions and had lost their privilege to drive a motor vehicle, resorted to bicycling, and had continued alcohol consumption despite negative previous consequences. METHODS: We retrospectively collected data on injured bicyclists older than 18 years with positive blood alcohol content levels treated from the period January 2009 to June 2014 at a large Level 1 urban trauma center. We then matched each patient by name and date of birth and were able to obtain public criminal records through the Superior Court of California for the local of county. RESULTS: A total of 149 injured bicyclists with positive blood alcohol levels were identified. Their average blood alcohol content was 236.0 mg/dL, and their average age was 41 years. Sixty-six (44.2%) of these patients had prior DUI/DWI convictions with suspension of driving privileges. Ninety-five patients in this group (63.8%) had no health insurance, and 51 patients (34.2%) tested positive for other drugs. Intoxicated bicyclists trended toward longer hospital length compared with nonintoxicated bicyclists (4.60 vs. 3.44 days; p = 0.07). Three (0.02%) of 149 patients were charged with bicycling while intoxicated. CONCLUSION: Intoxicated bicyclists involved in trauma are more likely to have a previous DUI/DWI, have other drug use, tend to have longer hospital stays, and are less likely to have insurance. Bicycle safety education and behavior modification targeting DUI/DWI offenders are warranted. In order to promote injury prevention, resources to increase awareness of this underestimated public health issue should be promoted. LEVEL OF EVIDENCE: Epidemiologic study, level III. PMID- 27389140 TI - A brief history of Forging New Frontiers, the annual conference of the Injury Free Coalition for Kids. AB - The Injury Free Coalition for Kids Annual Conference has contributed to the dissemination of information pertaining to the development of the field of injury prevention. A content analysis was completed using conference agendas used during the span of 2005-2015, finding that more than 398 presentations covering a wide variety of injuries have taken place. Published work has appeared in the Journal of Trauma and there has been recognition of people who have contributed to the development of the field. Forging New Frontiers is a valuable tool for attendees to exchange information about injury prevention. PMID- 27389141 TI - Guillain-Barre and Miller Fisher syndromes in patients with anti-hepatitis E virus antibody: a hospital-based survey in Japan. AB - There have been reports from several countries that hepatitis E virus (HEV) infection is frequently associated with Guillain-Barre syndrome (GBS). This study aimed to determine the frequency of HEV infection associated with GBS in Japanese patients, and to clarify the clinical characteristics of these patients. Sera obtained from 63 patients with GBS or Miller Fisher syndrome (MFS) and 60 control subjects were examined for both HEV-IgM and HEV-IgG. Of the 63 patients, three were positive for both HEV-IgM and elevated hepatic enzymes: Two had GBS, and one had MFS. No control subjects were positive for HEV-IgM. Our study demonstrated that 4.8 % of patients with GBS or MFS from our institution had associated acute HEV infection. There were no clinical differences between GBS with HEV infection and other GBS cases. To our knowledge, this is the first survey in Japan of HEV associated GBS or MFS. PMID- 27389142 TI - Primary Desmoid-Type Fibromatosis of the Mesentery: Report of an Unusual Tumor Localization. PMID- 27389143 TI - Cerium oxide nanoparticles with antioxidant properties ameliorate strength and prolong life in mouse model of amyotrophic lateral sclerosis. AB - Cerium oxide nanoparticles (CeNPs) neutralize reactive oxygen and nitrogen species. Since oxidative stress plays a role in amyotrophic lateral sclerosis (ALS) in humans and in the SOD1G93A mouse model of ALS, we tested whether administration of CeNPs would improve survival and reduce disease severity in SOD1G93A transgenic mice. Twice a week intravenous treatment of SOD1G93A mice with CeNPs started at the onset of muscle weakness preserved muscle function and increased longevity in males and females. Median survival after the onset of CeNP treatment was 33.0+/-3.7days (N=20), and only 22.0+/-2.5days in mice treated with vehicle, control injections (N=27; P=0.022). Since these citrate-EDTA stabilized CeNPs exhibited catalase and oxidase activity in cell-free systems and in in vitro models of ischemic oxidative stress, we hypothesize that antioxidant activity is the protective mechanism prolonging survival in the SOD1G93A mice. PMID- 27389144 TI - Nanoparticle formulation of small DNA molecules, Dbait, improves the sensitivity of hormone-independent prostate cancer to radiotherapy. AB - Intensification of radiotherapy has been shown to improve prostate cancer (PCa) outcomes. We hypothesized that we could further improve radiotherapy efficacy through the use DNA repair inhibitors. In this study, we evaluated the use of a new class of DNA damage repair inhibitor, nanoparticle (NP) Dbait, in radiosensitization of PCa. NP Dbait was formulated using H1 nanopolymer (folate polyethylenimine600-cyclodextrin). We demonstrated that NP Dbait was a potent radiosensitizer in vitro by colony forming assay using PCa cell lines. The result was validated in vivo using mouse xenograft models of PCa and we showed that NP Dbait significantly suppressed tumor growth and prolonged survival. Western blot, immunofluorescence and immunohistochemistry showed that NP Dbait inhibited DNA damage repair signaling pathways by mimicking DNA double-strand breaks. Our study supports further investigations of NP Dbait in improving the therapeutic efficacy of cancer radiotherapy. PMID- 27389145 TI - Spatiotemporal PFQNM visualization of the effect of suicide dendriplexes on dividing HeLa cells. AB - Suicide gene delivery is significant in cancer therapy but has not been fully investigated on a cellular scale. Here, Peak Force Quantitative Nanomechanical atomic force microscopy (PFQNM-AFM) was applied to visualize the effect of herpes simplex virus thymidine kinase dendriplexes (G4AcFaHSTK) on the morphological and nanomechanical properties of individual live and dividing HeLa cells. Cells were then exposed to G4AcFaHSTK, followed by ganciclovir, and directly imaged by real time PFQNM-AFM. Cell membrane liquefaction, cytoplasmic shrinkage, and cytoskeleton structure loss were observed during cell division. The average Young's modulus of the nuclear region increased with time as the cell continued from metaphase (6.29 kPa) to telophase (13.6 kPa) and then decreased (2.25 kPa) upon apoptosis. In contrast, cells exposed to either ganciclovir or G4AcFaHSTK alone have no changes. Thus, understanding the real-time effects of suicide dendriplexes on the cytoskeletal and nanomechanical behaviors of cancer cells may provide new methods for cancer treatment. PMID- 27389146 TI - Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo. AB - In this study, a folate targeted cyclodextrin (CD) nanoparticle was prepared by co-formulating CD.siRNA complexes with DSPE-PEG5000-folate to target the prostate specific membrane antigen (PSMA). Targeted formulations showed increased uptake, relative to untargeted controls, in two prostate cancer cell lines expressing PSMA (VCaP and LNCaP). Competitive uptake studies, using excess folate, significantly reduced uptake of targeted nanoparticles in PSMA positive cell lines (P<0.001). Relative to untreated controls, folate-targeted nanoparticles significantly reduced the levels of RelA mRNA in VCaP and LNCaP cells by 44% and 22% respectively (P<0.001). In contrast there was no significant reduction in RelA mRNA in these cell lines by untargeted complexes. Pharmacokinetic (PK) data indicated that the incorporation of PEG into the formulation increased the circulation time of siRNA 8-fold. This study highlights the ability of incorporating a folate ligand into CD.siRNA nanoparticles to allow for targeted delivery of siRNA to prostate cancer cells via the PSMA. PMID- 27389147 TI - A unique highly hydrophobic anticancer prodrug self-assembled nanomedicine for cancer therapy. AB - In contrast with common thought, we generated highly hydrophobic anticancer prodrug self-assembled nanoparticles without the aid of surface active substances, based on the conjugation of docetaxel to d-alpha-tocopherol succinate. The reduction-sensitive prodrug was synthesized with a disulfide bond inserted into the linker and was compared with a control reduction-insensitive prodrug. The morphology and stability of self-assembled nanoparticles were investigated. Cytotoxicity and apoptosis assays showed that the reduction sensitive nanoparticles had higher anticancer activity than the reduction insensitive nanoparticles. The reduction-sensitive nanoparticles exhibited favorable in vivo antitumor activity and tolerance compared with docetaxel Tween80-containing formulation and the reduction-insensitive nanoparticles. Taken together, the unique nanomedicine demonstrated a number of advantages: (i) ease and reproducibility of preparation, (ii) high drug payload, (iii) superior stability, (iv) prolonged circulation, and (v) improved therapeutic effect. This highly reproducible molecular assembly strategy should motivate the development of new nanomedicines. PMID- 27389148 TI - Nanometer-grooved topography stimulates trabecular bone regeneration around a concave implant in a rat femoral medulla model. AB - In the present study, a method was developed to reproduce two nanogrooved patterns (groove width/ridge width/depth: 150/150/50 nm and 200/800/70 nm) into cylindrical epoxy resin implants, which were subsequently coated with 20 nm of titanium. Also, implants with a conventional surface roughness (Rq=1.6 MUm) were produced. After cytocompatibility analysis of the produced surfaces, implants were installed into the femoral condyle of rats for 4 and 8 weeks. The histomorphometrical analysis of bone volume in a 100 MUm wide zone close to the implant surface showed that only for the 200/800 grooves the amount of bone increased significantly between 4 and 8 weeks of implantation. In addition, at the late time point only implants with the 200/800 pattern revealed a significantly higher bone volume compared to the rough controls. In conclusion, the 200/800 grooved pattern can positively influence bone volume adjacent to the implant surface, and should be evaluated and optimized in further (pre-)clinical studies. PMID- 27389149 TI - Schwann cells and neurite outgrowth from embryonic dorsal root ganglions are highly mechanosensitive. AB - Biochemical interactions between Schwann cells (SCs) and their substrate are crucial for the peripheral nervous systems (PNS). They are among the major parameters used in the design of nerve grafts for nerve injuries treatment, yet with unsatisfactory success despite pressing need worldwide. Mounting evidence demonstrates the fundamental physiological importance of mechanical cell substrate interactions. Substrate stiffness modulates cell differentiation, development, maintenance and regeneration. Mechanosensitivity may therefore be a key parameter to advancing nerve graft research. However, very little is known about PNS mechanosensitivity. Here, we explore mechanosensitivity of SCs and embryonic dorsal root ganglions (DRGs) under constant biochemical conditions but varying substrate stiffness adjusted to their physiological-developmental nature. We found SC stiffness, morphology, adhesion, motility, and neurite outgrowth from DRGs to be strongly substrate stiffness-dependent. These initial observations refine our knowledge of PNS physiology, development and regeneration, and demonstrate promise for advancing nerve grafts. PMID- 27389150 TI - Non-viral magnetic engineering of endothelial cells with microRNA and plasmid-DNA An optimized targeting approach. AB - Genetic modulation of angiogenesis is a powerful tool for the treatment of multiple disorders. Here, we describe a strategy to produce modified endothelial cells, which can be efficiently magnetically guided. First, we defined optimal transfection conditions with both plasmid and microRNA, using a polyethyleneimine/magnetic nanoparticle-based vector (PEI/MNP), previously designed in our group. Further, two approaches were assessed in vitro: direct vector guidance and magnetic targeting of transfected cells. Due to its higher efficiency, including simulated dynamic conditions, production of miR/PEI/MNP modified magnetically responsive cells was selected for further detailed investigation. In particular, we have studied internalization of transfection complexes, functional capacities and intercellular communication of engineered cells and delivery of therapeutic miR. Moreover, we demonstrated that 104 miRNA/PEI/MNP-modified magnetically responsive cells loaded with 0.37pg iron/cell are detectable with MRI. Taken together, our in vitro findings show that PEI/MNP is highly promising as a multifunctional tool for magnetically guided angiogenesis regulation. PMID- 27389151 TI - Someone is following us, aren't they? PMID- 27389152 TI - Prediction of recurrence after cryoballoon ablation therapy in patients with paroxysmal atrial fibrillation. PMID- 27389153 TI - Cardiac findings in patients with Behcet's disease: Facts and controversies. AB - Behcet's disease (BD) is a systemic vasculitis of unknown etiology. It is characterized by recurrent oral and genital ulcers, uveitis, and a number of systemic manifestations. Although the disease is recognized worldwide, its prevalence is highly variable. A detailed review and analysis of the worldwide published reports on BD showed that not only the prevalence of the disease but also its cardiac complications differ according to the geographic distribution of the studied population. With the exception of France, Greece, Spain, and Italy, very few reports and studies regarding BD have been published from the western countries. Cardiovascular complications are an important cause of poor outcome in patients with BD. Over the past few years, many case reports and studies have been published, providing more facts about these complications. For example, peculiar echocardiographic findings in patients with aortic valve regurgitation and intracardiac thrombi secondary to BD were recently described. The role of these findings in the initial diagnosis of the disease, however, remains to be evaluated. On the other hand, some reports present contradictory results, especially concerning the left ventricular diastolic function, pathogenesis of coronary artery disease, and proper management of the cardiac complications in BD. Importantly, management of these complications is based mainly on the discretion of the treating physician due to the absence of large controlled studies and clear guidelines. This approach sometimes creates inconsistent data and allows controversies to persist. The review presented here will discuss some of the facts and controversies related to cardiac complications in BD. PMID- 27389155 TI - Acute myocardial infarction and ischemic stroke coexistence due to marijuana abuse in an adolescent. PMID- 27389154 TI - Non-alcoholic fatty liver disease-From the cardiologist perspective. AB - Non-alcoholic fatty liver disease (NAFLD) includes a range of disorders characterized by excess accumulation of triglycerides within the liver. While simple steatosis may be clinically stable, non-alcoholic steatohepatitis (NASH) can be progressive. Inflammation is believed to be the driving force behind NASH and the progression to fibrosis and subsequent cirrhosis. NAFLD is globally considered a significant health concern not only because of its incidence but also because of its economic impact. The fact that NAFLD is associated with cardiovascular disease is widely recognized, as well as the fact that NAFLD patient mortality rises when such an association is present. In particular, NAFLD is associated with coronary and carotid atherosclerosis, endothelial dysfunction and arterial rigidity, ventricles function, valves morphology, congestive heart failure, and arrhythmias (especially atrial fibrillation). Additionally, the hypercoagulability status in NAFLD patient may be suggested by the presence of inflammatory and coagulation markers. In order to differentiate between milder forms and the more severe ones that necessitate aggressive therapy, individualized risk scores may be used. This narrative review will analyze and interpret the papers published in PubMed in the last 16 years, in an attempt to expand our understanding of the NASH as a possible cardiovascular risk factor. PMID- 27389156 TI - Severe hypocalcemia and hypercalciuria due to contrast medium in the course of acute myocardial infarction. PMID- 27389157 TI - Coronary-subclavian steal syndrome in a hemodialysis patient with ipsilateral subclavian artery occlusion and contralateral vertebral artery stenosis "Case Report". PMID- 27389158 TI - Can neutrophil-to-lymphocyte ratio be a valuable marker in defining peripheral artery disease severity? PMID- 27389159 TI - Author's Reply. PMID- 27389160 TI - Mitral annular calcification: left atrial size and left ventricular dysfunction. PMID- 27389161 TI - Author's Reply. PMID- 27389162 TI - Postoperative atrial fibrillation may be associated with other factors. PMID- 27389163 TI - Author's Reply. PMID- 27389164 TI - Effects of energy drinks on blood pressure, heart rate, and electrocardiographic parameters: an experimental study on healthy young adults. PMID- 27389165 TI - Author's Reply. PMID- 27389166 TI - When is the best time to mobilize patients after myocardial infarction? An issue that merits further research. PMID- 27389168 TI - In Reference to Hyoid surgery alone for obstructive sleep apnea: A systematic review and meta-analysis. PMID- 27389167 TI - The role of modulation of antioxidant enzyme systems in the treatment of neurodegenerative diseases. AB - Oxidative stress is a much-appreciated phenomenon associated with the progression of neurodegenerative diseases (NDDs) due to imbalances in redox homeostasis. The poor correlations between the in vitro benefits and clinical trials of direct radical scavengers have prompted research into indirect antioxidant enzymes such as Nrf2. Activation of Nrf2 leads to the upregulation of a myriad of cytoprotective and antioxidant enzymes/proteins. Traditionally, early Nrf2 activators were studied as chemoprotective agents. There is a consequential lack of clinical trials testing Nrf2 activation in NDDs. However, there is abundant evidence of their utility in pre-clinical studies. Herein, we review the endogenous Nrf2 regulatory pathway and avenues for targeting this pathway. Furthermore, we provide updated information on pre-clinical studies for natural and synthetic Nrf2 activators. On the basis of our findings, we posit that successful therapeutics for NDDs rely on the design of potent synthetic Nrf2 activators with a careful combination of other neuroprotective activities. PMID- 27389169 TI - Recombinant polymorphic membrane protein D in combination with a novel, second generation lipid adjuvant protects against intra-vaginal Chlamydia trachomatis infection in mice. AB - The development of a chlamydial vaccine that elicits protective mucosal immunity is of paramount importance in combatting the global spread of sexually transmitted Chlamydia trachomatis (Ct) infections. While the identification and prioritization of chlamydial antigens is a crucial prerequisite for efficacious vaccine design, it is likely that novel adjuvant development and selection will also play a pivotal role in the translational potential of preclinical Ct vaccines. Although the molecular nature of the immuno-modulatory component is of primary importance, adjuvant formulation and delivery systems may also govern vaccine efficacy and potency. Our study provides the first preclinical evaluation of recombinant Ct polymorphic membrane protein D (rPmpD) in combination with three different formulations of a novel second-generation lipid adjuvant (SLA). SLA was rationally designed in silico by modification of glucopyranosyl lipid adjuvant (GLA), a TLR4 agonistic precursor molecule currently in Phase II clinical development. We demonstrate robust protection against intra-vaginal Ct challenge in mice, evidenced by significantly enhanced resistance to infection and reduction in mean bacterial load. Strikingly, protection was found to correlate with the presence of robust anti-rPmpD serum and cervico-vaginal IgG titres, even in the absence of adjuvant-induced Th1-type cellular immune responses elicited by each SLA formulation, and we further show that anti-rPmpD antibodies recognize Ct EBs. These findings highlight the utility of SLA and rational molecular design of adjuvants in preclinical Ct vaccine development, but also suggest an important role for anti-rPmpD antibodies in protection against urogenital Ct infection. PMID- 27389170 TI - Polio Eradication Initiative: Contribution to improved communicable diseases surveillance in WHO African region. AB - INTRODUCTION: Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, there has been a tremendous progress in the reduction of cases of poliomyelitis. The world is on the verge of achieving global polio eradication and in May 2013, the 66th World Health Assembly endorsed the Polio Eradication and Endgame Strategic Plan (PEESP) 2013-2018. The plan provides a timeline for the completion of the GPEI by eliminating all paralytic polio due to both wild and vaccine-related polioviruses. METHODS: We reviewed how GPEI supported communicable disease surveillance in seven of the eight countries that were documented as part of World Health Organization African Region best practices documentation. Data from WHO African region was also reviewed to analyze the performance of measles cases based surveillance. RESULTS: All 7 countries (100%) which responded had integrated communicable diseases surveillance core functions with AFP surveillance. The difference is on the number of diseases included based on epidemiology of diseases in a particular country. The results showed that the polio eradication infrastructure has supported and improved the implementation of surveillance of other priority communicable diseases under integrated diseases surveillance and response strategy. CONCLUSION: As we approach polio eradication, polio-eradication initiative staff, financial resources, and infrastructure can be used as one strategy to build IDSR in Africa. As we are now focusing on measles and rubella elimination by the year 2020, other disease-specific programs having similar goals of eradicating and eliminating diseases like malaria, might consider investing in general infectious disease surveillance following the polio example. PMID- 27389171 TI - Polio Eradication Initiative contribution in strengthening immunization and integrated disease surveillance data management in WHO African region, 2014. AB - INTRODUCTION: The PEI Programme in the WHO African region invested in recruitment of qualified staff in data management, developing data management system and standards operating systems since the revamp of the Polio Eradication Initiative in 1997 to cater for data management support needs in the Region. This support went beyond polio and was expanded to routine immunization and integrated surveillance of priority diseases. But the impact of the polio data management support to other programmes such as routine immunization and disease surveillance has not yet been fully documented. This is what this article seeks to demonstrate. METHODS: We reviewed how Polio data management area of work evolved progressively along with the expansion of the data management team capacity and the evolution of the data management systems from initiation of the AFP case based to routine immunization, other case based disease surveillance and Supplementary immunization activities. RESULTS: IDSR has improved the data availability with support from IST Polio funded data managers who were collecting them from countries. The data management system developed by the polio team was used by countries to record information related to not only polio SIAs but also for other interventions. From the time when routine immunization data started to be part of polio data management team responsibility, the number of reports received went from around 4000 the first year (2005) to >30,000 the second year and to >47,000 in 2014. CONCLUSION: Polio data management has helped to improve the overall VPD, IDSR and routine data management as well as emergency response in the Region. As we approach the polio end game, the African Region would benefit in using the already set infrastructure for other public health initiative in the Region. PMID- 27389172 TI - Effects of serostatus and gender on the HRV-16-induced local immune response. AB - The "experimental cold model" is widely used to investigate effects of HRV infection. However, effects of serostatus and gender on the HRV-induced immune response have not been clarified. 40 healthy seropositive and seronegative (1:1) male and female (1:1) subjects were inoculated with HRV-16. HRV infection increased viral load in nasal wash, which tended to be more pronounced in seronegative subjects. Furthermore, HRV infection increased levels of IP-10, IL 6, and IL-10 and leukocyte numbers in nasal wash of seronegative, but not of seropositive subjects. No differences in any of the parameters were found between both sexes. The HRV-induced local immune response is diminished in seropositive subjects compared with seronegative subjects, while gender does not influence this response. These results have important implications for the design of future experimental cold studies: seronegative subjects, from both sexes can be included. PMID- 27389173 TI - Melanoma-specific mortality and competing mortality in patients with non metastatic malignant melanoma: a population-based analysis. AB - BACKGROUND: The objectives of this study were to evaluate and model the probability of melanoma-specific death and competing causes of death for patients with melanoma by competing risk analysis, and to build competing risk nomograms to provide individualized and accurate predictive tools. METHODS: Melanoma data were obtained from the Surveillance Epidemiology and End Results program. All patients diagnosed with primary non-metastatic melanoma during the years 2004 2007 were potentially eligible for inclusion. The cumulative incidence function (CIF) was used to describe the probability of melanoma mortality and competing risk mortality. We used Gray's test to compare differences in CIF between groups. The proportional subdistribution hazard approach by Fine and Gray was used to model CIF. We built competing risk nomograms based on the models that we developed. RESULTS: The 5-year cumulative incidence of melanoma death was 7.1 %, and the cumulative incidence of other causes of death was 7.4 %. We identified that variables associated with an elevated probability of melanoma-specific mortality included older age, male sex, thick melanoma, ulcerated cancer, and positive lymph nodes. The nomograms were well calibrated. C-indexes were 0.85 and 0.83 for nomograms predicting the probability of melanoma mortality and competing risk mortality, which suggests good discriminative ability. CONCLUSIONS: This large study cohort enabled us to build a reliable competing risk model and nomogram for predicting melanoma prognosis. Model performance proved to be good. This individualized predictive tool can be used in clinical practice to help treatment-related decision making. PMID- 27389174 TI - Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy. AB - : Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median Cmax and Ctrough values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher Cmax and Ctrough values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00410163). PMID- 27389175 TI - Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. AB - It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia. PMID- 27389176 TI - Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment. AB - Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of umol O2/min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO2-inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction. PMID- 27389177 TI - Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis. AB - A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen's k statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593-0.867; reader one) and 0.708 (95% CI = 0.561-0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease. PMID- 27389178 TI - Losartan improves cerebrovascular function in a mouse model of Alzheimer's disease with combined overproduction of amyloid-beta and transforming growth factor-beta1. AB - Alterations of the renin-angiotensin system have been implicated in the pathogenesis of Alzheimer's disease. We tested the efficacy of losartan (10 mg/kg/day for three months), a selective angiotensin II type 1 receptor antagonist, in alleviating cerebrovascular and cognitive deficits in double transgenic mice (six months at endpoint) that overexpress a mutated form of the human amyloid precursor protein (APPSwe,Ind) and a constitutively active form of the transforming growth factor-beta1, thereafter named A/T mice. Losartan rescued cerebrovascular reactivity, particularly the dilatory responses, but failed to attenuate astroglial activation and to normalize the neurovascular uncoupling response to sensory stimulation. The cognitive deficits of A/T mice were not restored by losartan nor were the increased brain levels of soluble and insoluble Abeta1-40 and Abeta1-42 peptides normalized. Our results are the first to demonstrate the capacity of losartan to improve cerebrovascular reactivity in an Alzheimer's disease mouse model of combined Abeta-induced vascular oxidative stress and transforming growth factor-beta1-mediated vascular fibrosis. These data suggest that losartan may be promising for restoring cerebrovascular function in patients with vascular diseases at risk for vascular dementia or Alzheimer's disease. However, a combined therapy may be warranted for rescuing both vascular and cognitive deficits in a multifaceted pathology like Alzheimer's disease. PMID- 27389180 TI - Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients. AB - In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson's chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo , hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging. PMID- 27389179 TI - Recombinant Gas6 augments Axl and facilitates immune restoration in an intracerebral hemorrhage mouse model. AB - Axl, a tyrosine kinase receptor, was recently identified as an essential component regulating innate immune response. Suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 are potent Axl-inducible negative inflammatory regulators. This study investigated the role of Axl signaling pathway in immune restoration in an autologous blood-injection mouse model of intracerebral hemorrhage. Recombinant growth arrest-specific 6 (Gas6) and R428 were administrated as specific agonist and antagonist. In vivo knockdown of Axl or suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 by siRNA was applied. After intracerebral hemorrhage, the expression of endogenous Axl, soluble Axl, and Gas6 was increased, whereas the expression of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 was inhibited. Recombinant growth arrest-specific 6 administration alleviated brain edema and improved neurobehavioral performances. Moreover, enhanced Axl phosphorylation with cleavage of soluble Axl (sAxl), and an upregulation of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 were observed. In vivo knockdown of Axl and R428 administration both abolished the effect of recombinant growth arrest-specific 6 on brain edema and also decreased the expression suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3. In vivo knockdown of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 aggravated cytokine releasing despite of recombinant growth arrest-specific 6. In conclusion, Axl plays essential role in immune restoration after intracerebral hemorrhage. And recombinant growth arrest specific 6 attenuated brain injury after intracerebral hemorrhage, probably by enhancing Axl phosphorylation and production of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3. PMID- 27389182 TI - Preoperative Predictors and Outcome of Triple Valve Surgery in 487 Consecutive Patients. AB - Background Triple valve surgery (TVS) is associated with an elevated risk for operative mortality and thus remains a surgical challenge. We report our experience and results of TVS procedures, especially with respect to identification of preoperative risk factors, to improve patient selection. Methods Between December 1994 and January 2013, 487 consecutive patients (240 male, 247 female) underwent TVS at the Heart Center Leipzig, University of Leipzig. The data were prospectively collected and retrospectively analyzed. Univariate and multivariable regression analyses were performed to identify risk factors. Results The 30-day mortality was 16.1% and the long-term survival at 1 year and 5 years was 71.8% and 54.6%, respectively. Multivariable logistic regression analysis identified previous myocardial infarction to be the only significant predictor for early mortality. Age, New York Heart Association functional class IV, previous myocardial infarction, dialysis, and liver dysfunction were identified as preoperative predictors for late mortality. Furthermore, an increase of operative risk, given for each year, was observed during the study period. In contrast, 30-day mortality decreased during the observation time. Conclusion TVS is associated with a high surgical risk. Long term survival is decreased, but acceptable for these high-risk patients. The series demonstrates that increasing surgical risk, age, and comorbidities are the future challenges in TVS. PMID- 27389181 TI - Ischemia-induced spreading depolarization in the retina. AB - Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 +/- 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients. PMID- 27389183 TI - Enhancement of light absorption by blood to Nd:YAG laser using PEG-modified gold nanorods. AB - BACKGROUND AND OBJECTIVE: On the basis of the principle of selective photothermolysis, laser therapy has been the most effective treatment strategy for Port-wine stains (PWSs) caused by the expansion of dermal capillaries. Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser at 1064 nm wavelength has great potential for deeply buried PWS, although its application is limited because of its weak absorption by blood. The purpose of this study is to investigate the effect of PEG-modified gold nanorods (NRs) on the blood absorption enhancement for Nd:YAG laser. MATERIALS AND METHODS: PEG-modified gold nanorods (NRs) were synthesized via the seeded growth method. Then, the effect of PEG-modified gold NRs on blood light absorbance was investigated through adding different concentration of PEG-modified gold NRs to 1 ml of blood at room temperature. Finally, the optical properties of whole mice blood with or without PEG-modified gold NRs under slow heating were investigated. RESULTS: The average length and width of PEG-modified gold NRs are 79.5 +/- 10.5 and 13.5 +/- 0.9 nm, respectively, with the aspect ratio of 5.89, and a strong absorption peak exists at ~1050 nm in the near-infrared range. A linear correlation between the blood absorbance at 1064 nm and the amount of PEG-modified gold NRs was obtained. The absorbance at 1064 nm increased 17.6, 33.0, 48.3, and 65.4 times when 0.4, 0.8, 1.2, and 1.6 mg of PEG-modified gold NRs was added to 1 ml of blood at room temperature, respectively. After adding 0.8 mg of PEG-modified gold NRs to 1 ml of blood, blood absorbance at 1064 nm at different temperatures increased by an average of 24.0 times. After intravenously injecting PEG-modified gold NRs (0.87 mg/ml) into Sprague-Dawley mice, the blood absorbance at 1064 nm increased from 0.014 to 0.5. CONCLUSION: Our findings suggest that PEG-modified gold NRs injection is an efficient way to enhance light absorption by blood to Nd:YAG laser. Lasers Surg. Med. 48:790-803, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27389184 TI - Incomplete Cleft Earlobe Reconstruction Using a Z-plasty or Hammock Flap. PMID- 27389185 TI - Microdialysis combined with UPLC-MS/MS method for determination of tetramethylpyrazine and ferulic acid in striatum of awake and anesthetic rats subjected to cerebral ischemia. AB - A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination and pharmacokinetic investigation of Tetramethylpyrazine (TMP) and Ferulic acid (FA) in rat striatum. The method was validated over the concentration range of 1.15-505ng/mL for TMP and 3.23-101ng/mL for FA, with a lower limit of quantitation (LLOQ) of 1.15ng/mL and 3.23ng/mL, respectively. This method can be successfully applied in pharmacokinetic studies of TMP and FA in striatum of awake and anesthetic rats. The cerebral blood flow velocity (CBF) during middle cerebral artery occlusion (MCAO) was monitored by Laser speckle contrast imaging, to observe whether the compatibility of TMP and FA could improve CBF against cerebral ischemia/reperfusion (I/R) injury. Infarct volume was examined to evaluate severity of ischemic brain injury. The pharmacokinetic study indicated that T1/2, Cmax, MRT and AUC0-inf were changed after combined administration of TMP and FA, when compared with either drug alone both in awake and anesthetic groups. The pharmacodynamics results showed that co-administration of drugs could enhance the CBF during middle cerebral artery occlusion and reduced the infarct volume. Taken together, the compatibility treatment of TMP and FA might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize the compatibility proportion. PMID- 27389187 TI - A New Species of Paracoccus Ezzat and McConnell (Hemiptera: Pseudococcidae) from Southern Brazil. AB - The worldwide mealybug genus Paracoccus Ezzat & McConnell (Hemiptera: Coccomorpha: Pseudococcidae) has eight described Neotropical species, including two species known from Brazil. In this article, we describe a third species from Brazil: Paracoccus galzerae Pacheco da Silva & Kaydan sp. n., based on the morphology of adult females collected on the roots of Conyza bonariensis (Asteraceae) in vineyards in Bento Goncalves City, Rio Grande do Sul. A revised identification key including the new species is provided for the Neotropical region. PMID- 27389186 TI - The Interaction between Childhood Bullying and the FKBP5 Gene on Psychotic-Like Experiences and Stress Reactivity in Real Life. AB - AIM: The present study employed Experience Sampling Methodology to examine whether the interaction between childhood bullying and FKBP5 variability (i) is associated with the expression of psychotic-like experiences, paranoia, and negative affect, and (ii) moderates psychotic-like, paranoid, and affective reactivity to different forms of momentary stress (situational and social) in daily life. METHODS: A total of 206 nonclinical young adults were interviewed for bullying with the Childhood Experience of Care and Abuse and were prompted randomly eight times daily for one week to complete assessments of their current experiences, affect, and stress appraisals. Participants were genotyped for three FKBP5 single nucleotide polymorphisms (SNPs) (rs3800373, rs9296158, and rs1360780) that have been linked to hypothalamus-pituitary-adrenal axis reactivity. Multilevel analyses were conducted to examine the effect of the interaction between childhood bullying and the FKBP5 haplotype derived from these three SNPs. RESULTS: The interaction between bullying and the FKBP5 haplotype was associated with positive, but not negative, psychotic-like experiences, paranoia, and negative affect. The bullying x FKBP5 interaction also moderated the association of a social stress appraisal (specifically, being alone because people do not want to be with you) with psychotic-like experiences and negative affect in daily life. Simple slopes analyses indicated that, in all cases, the associations were significantly increased by exposure to bullying in participants with the risk haplotype, but not for those with the non-risk haplotype. DISCUSSION: The present study provides the first evidence of the interplay between childhood bullying and FKBP5 variability in the real-world expression of psychosis proneness and social stress reactivity. The findings underscore the importance of investigating how gene-environment interactions are involved in mechanistic pathways to the extended psychosis phenotype and lend further support to the increasing relevance given to socially defeating appraisals in the experience of reality distortion. PMID- 27389188 TI - Susceptibility and Interactions of Drosophila suzukii and Zaprionus indianus (Diptera: Drosophilidae) in Damaging Strawberry. AB - Drosophila suzukii (Matsumura) has been recently detected causing damage to strawberries in Brazil. Infestation in strawberry culture has often been observed jointly with the presence of Zaprionus indianus Gupta. This study investigated the susceptibility of strawberries at three ripening stages to infestation of D. suzukii and Z. indianus and their interaction. In the laboratory, strawberries cv. Albion at different ripening stages (green, semi-ripe and ripe) were exposed to D. suzukii and Z. indianus for 24 h in choice and no-choice bioassays. Additionally, we evaluated the effects of mechanical damage incurred artificially or by D. suzukii oviposition on Z. indianus infestation. In no-choice bioassay, there were no significant differences in fruit susceptibility to D. suzukii infestation at different ripening stages. However, in choice bioassay, D. suzukii adults preferred to oviposit on R fruit. The presence of mechanical damage did not increase susceptibility of fruit to D. suzukii oviposition. For Z. indianus, there was greater susceptibility of R fruit in relation to SR and G fruit in both the choice and no-choice bioassays. There was a significant and positive interaction of mechanical damage and damage caused by D. suzukii to R fruit and infestation by Z. indianus, which was not observed in SR and G fruit. Although infestation of Z. indianus is related to attack damaged or decaying fruit, this work shows that this species has the ability to oviposit and develop in healthy strawberry fruit with and increased infestation level when the fruit has damage to its epidermis. PMID- 27389189 TI - Conjugating Prussian blue nanoparticles onto antigen-specific T cells as a combined nanoimmunotherapy. AB - AIM: To engineer a novel nanoimmunotherapy comprising Prussian blue nanoparticles (PBNPs) conjugated to antigen-specific cytotoxic T lymphocytes (CTL), which leverages PBNPs for their photothermal therapy (PTT) capabilities and Epstein Barr virus (EBV) antigen-specific CTL for their ability to traffic to and destroy EBV antigen-expressing target cells. MATERIALS & METHODS: PBNPs and CTL were independently biofunctionalized. Subsequently, PBNPs were conjugated onto CTL using avidin-biotin interactions. The resultant cell-nanoparticle construct (CTL:PBNPs) were analyzed for their physical, phenotypic and functional properties. RESULTS: Both PBNPs and CTL maintained their intrinsic physical, phenotypic and functional properties within the CTL:PBNPs. CONCLUSION: This study highlights the potential of our CTL:PBNPs nanoimmunotherapy as a novel therapeutic for treating virus-associated malignancies such as EBV+ cancers. PMID- 27389190 TI - RhoA deficiency disrupts podocyte cytoskeleton and induces podocyte apoptosis by inhibiting YAP/dendrin signal. AB - BACKGROUND: Podocyte apoptosis is a major mechanism that leads to proteinuria in many kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. RhoA is one of Rho GTPases that has been well studied and plays a key role in regulating cytoskeletal architecture. Previous study showed that insufficient RhoA could result in rat aortic smooth muscle cell apoptosis. However, whether RhoA is involved in podocyte apoptosis remains unknown. METHODS: Culture podocytes were treated with LPS, ADR or siRNA for 48 h before harvest. Subcellular immunoblotting, qRT-PCR, immunofluorescence and flow cytometry were used to exam the expression and function of RhoA or YAP in podocytes. RESULTS: We found that the expression of RhoA and its activity were significantly decreased in LPS or ADR-injured podocytes, accompanying loss of stress fibers and increased cell apoptosis. Knocking down RhoA or its downstream effector mDia expression by siRNA also caused loss of stress fibers and podocyte apoptosis. Moreover, our results further demonstrated that RhoA deficiency could reduce the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Silenced dendrin expression significantly abolished RhoA, mDia or YAP deficiency-induced podocyte apoptosis. CONCLUSION: RhoA deficiency could disrupt podocyte cytoskeleton and induce podocyte apoptosis by inhibiting YAP/dendrin signal. RhoA/mDia/YAP/dendrin signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary RhoA would be one potent way to prevent proteinuria kidney diseases. PMID- 27389191 TI - Subclinical hypothyroidism is associated with higher carotid intima-media thickness in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). AB - BACKGROUND AND AIM: Although subclinical hypothyroidism (SCH) is associated with cardiovascular risk, there is scarce data about subclinical atherosclerosis in subjects with SCH. We aimed to analyze the association between SCH and carotid intima-media thickness (IMT) using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS AND RESULTS: We included subjects with normal thyroid function (TSH: 0.4-4.0 mIU/l, and normal free thyroxine (FT4): 0.8-1.9 ng/dl) and SCH (TSH >= 4.0 mIU/l and normal FT4) evaluated for IMT in a cross-sectional analysis. We excluded individuals using medications that affect thyroid function and those with a history of cardiovascular disease. We performed logistic and linear regression models to evaluate the association with IMT (mean values and categorized at the 75th percentile) as a dependent variable and SCH as an independent variable, adjusted for other cardiovascular risk factors. From 8623 subjects (median age of 50 years; interquartile range: 44-57), 4624 (53.6%) were women, 8095 (93.9%) were euthyroid, and 528 (6.1%) had SCH. Groups varied in age, body mass index, Framingham risk score, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein, as well as, IMT, that were all higher in SCH compared to euthyroid participants. SCH is associated with IMT as a continuous variable (beta = 0.010, P = 0.036) and IMT >75th percentile: OR = 1.30 (95% CI = 1.06-1.59) in logistic models. CONCLUSION: Individuals with SCH presented higher IMT compared with euthyroid subjects, even after adjustment for potential confounders. IMT was independently associated with SCH in the baseline of the ELSA-Brasil study. PMID- 27389192 TI - Activation of the IL-2 Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome? AB - The renal podocyte plays an important role in maintaining the structural integrity of the glomerular basement membrane. We have previously reported that patients with idiopathic nephrotic syndrome (INS) have increased IL-2 production. We hypothesized that podocytes express an IL-2 receptor (IL-2R) and signaling through this receptor can result in podocyte injury. To confirm the presence of the IL-2R, we tested a conditionally immortalized murine podocyte cell line by flow cytometry, qPCR, and Western blot. To test for the presence of the IL-2R in vivo, immunohistochemical staining was performed on human renal biopsies in children with FSGS and control. Podocytes were stimulated with IL-2 in vitro, to study signaling events via the JAK/STAT pathway. The results showed that stimulation with IL-2 resulted in increased mRNA and protein expression of STAT 5a, phosphorylated STAT 5, JAK 3, and phosphorylated JAK 3. We then investigated for signs of cellular injury and the data showed that pro-apoptotic markers Bax and cFLIP were significantly increased following IL-2 exposure, whereas LC3 II was decreased. Furthermore, mitochondrial depolarization and apoptosis were both significantly increased following activation of the IL-2R. We used a paracellular permeability assay to monitor the structural integrity of a podocyte monolayer following IL-2 exposure. The results showed that podocytes exposed to IL-2 have increased albumin leakage across the monolayer. We conclude that murine podocytes express the IL-2R, and that activation through the IL-2R results in podocyte injury. PMID- 27389193 TI - In Hospital and 3-Month Mortality and Functional Recovery Rate in Patients Treated for Hip Fracture by a Multidisciplinary Team. AB - OBJECTIVES: Medical comorbidities affect outcome in elderly patients with hip fracture. This study was designed to preliminarily evaluate the usefulness of a hip-fracture unit led by an internal medicine specialist. METHODS: In-hospital and 3-month outcomes in patients with hip fracture were prospectively evaluated in 121 consecutive patients assessed before and followed after surgery by a multidisciplinary team led by internal medicine specialist; 337 consecutive patients were recalled from ICD-9 discharge records and considered for comparison regarding in-hospital mortality. RESULTS: In the intervention period, patients treated within 48 hours were 54% vs. 26% in the historical cohort (P<0.0001). In hospital mortality remained stable at about 2.3 per 1000 person-days. At 3 months, 10.3% of discharged patients had died, though less than 8% of patients developed postoperative complications (mainly pneumonia and respiratory failure). The presence of more than 2 major comorbidities and the loss of 3 or more BADL were independent predictors of death. 50/105 patients recovered previous functional capacity, but no independent predictor of functional recovery could be identified. Mean length of hospital stay significantly decreased in comparison to the historical cohort (13.6+/- 4.7 vs 17 +/- 5 days, p = 0.0001). Combined end point of mortality and length of hospitalization < 12 days was significantly lower in study period (27 vs 34%, p <0.0132). CONCLUSIONS: Identification and stabilization of concomitant clinical problems by internal medicine specialists may safely decrease time to surgery in frail subjects with hip fracture. Moreover, integrated perioperative clinical management may shorten hospital stay with no apparent increase in in-hospital mortality and ultimately improve the outcome. These results are to be confirmed by a larger study presently ongoing at our institution. PMID- 27389195 TI - Escaping Host Immunity: New Tricks for Plant Pathogens. PMID- 27389197 TI - Editorial: Remembering John C. Light. I. Editorial contributions. PMID- 27389194 TI - Drug-induced liver injury associated with Complementary and Alternative Medicine: a review of adverse event reports in an Asian community from 2009 to 2014. AB - BACKGROUND: The use of Complementary and Alternative Medicine (CAM) has been increasing over the years. A recent review of adverse event reports (AERs) associated with CAM in Singapore found a notable number of AERs submitted. The objectives of this study are to analyse hepatotoxicity cases associated with CAM in Singapore based on spontaneous adverse event reporting to the Health Sciences Authority (HSA), and to highlight safety signals for specific herbal ingredients. METHODS: AERs associated with CAM and hepatotoxicity submitted to the Vigilance and Compliance Branch (VCB) of the HSA from 2009 to 2014 were compiled. The following information was extracted and analysed: Demographic information; time to onset; hospitalisation status; outcome; type of hepatotoxicity; ingredients of CAM, and the total daily doses (TDD); concurrent western medicines and health supplements; and reporter details. RESULTS: Fifty-seven reports were eligible for analysis. Thirty-five (61.4 %) cases involved Traditional Chinese Medicine (TCM). The Roussel Uclaf Causality Assessment Method was applied in 29 (82.9 %) of these cases, and the median score was 4 (range: 1-8). Chai Hu (Radix bupleuri) was suspected in 11 (31.4 %) cases. TDDs of most ingredients were within recommended doses of the Chinese Pharmacopoeia. CONCLUSIONS: Drug-induced liver injury is still poorly understood and more objective assessments are warranted. Reporting of adverse events should be strongly advocated to facilitate future analyses and the understanding of risk-benefit profiles of CAM. PMID- 27389196 TI - A comparison of sample collection methods for quantifying cell-free fetal neurodevelopment transcripts in amniotic fluid. AB - BACKGROUND: Cell-free RNA (cfRNA) transcripts known to be expressed by the fetal brain are detectable by quantitative reverse transcription PCR (RT-qPCR) in amniotic fluid and represent potential biomarkers of neurodevelopment. The aim of this study was to compare the cfRNA yields from amniotic fluid (AF) collected in a commercial RNA stabilization product with the traditional method of freezing alone. FINDINGS: Thirteen women undergoing elective Cesarean birth at term without labor had whole AF collected at the time of uterine incision, prior to membrane rupture. Patient samples were split between Streck RNA blood collection tubes (BCT) and plain sterile polypropylene centrifuge tubes. Cell-free RNA from the AF supernatant was extracted according to a previously published protocol. RT qPCR was performed for the reference gene GAPDH, and three genes associated with neurodevelopment (NRXN3, NTRK3, and ZBTB18). The yield from samples collected in Streck RNA BCT and plain centrifuge tubes were compared with the paired t test. GAPDH, NRXN3 and ZBTB18 amplified successfully in all samples, but NTRK3 did not. The RNA yield was significantly lower in samples collected in the Streck RNA BCT compared with the traditional storage method of freezing alone for all three successfully amplified genes (p < 0.0001). CONCLUSIONS: Selected cfRNA neurodevelopment transcripts are consistently detectable in third trimester AF. There appears to be no benefit in collecting AF in Streck RNA BCT for quantitative studies of AF cell-free RNA. PMID- 27389198 TI - Editorial: Remembering John C. Light. II. Scientific contributions. PMID- 27389199 TI - Communication: Charge-population based dispersion interactions for molecules and materials. AB - We introduce a system-independent method to derive effective atomic C6 coefficients and polarizabilities in molecules and materials purely from charge population analysis. This enables the use of dispersion-correction schemes in electronic structure calculations without recourse to electron-density partitioning schemes and expands their applicability to semi-empirical methods and tight-binding Hamiltonians. We show that the accuracy of our method is en par with established electron-density partitioning based approaches in describing intermolecular C6 coefficients as well as dispersion energies of weakly bound molecular dimers, organic crystals, and supramolecular complexes. We showcase the utility of our approach by incorporation of the recently developed many-body dispersion method [Tkatchenko et al., Phys. Rev. Lett. 108, 236402 (2012)] into the semi-empirical density functional tight-binding method and propose the latter as a viable technique to study hybridorganic-inorganic interfaces. PMID- 27389200 TI - Communication: Towards catalytic nitric oxide reduction via oligomerization on boron doped graphene. AB - We use density functional theory to describe a novel way for metal free catalytic reduction of nitric oxide NO utilizing borondopedgraphene. The present study is based on the observation that borondopedgraphene and O-N=N-O(-) act as Lewis acid base pair allowing the graphene surface to act as a catalyst. The process implies electron assisted N=N bond formation prior to N-O dissociation. Two N2 + O2 product channels, one of which favoring N2O formation, are envisaged as outcome of the catalytic process. Besides, we show also that the N2 + O2formation pathways are contrasted by a side reaction that brings to N3O3 (-)formation and decomposition into N2O + NO2 (-). PMID- 27389201 TI - Communication: Toward an improved control of the fixed-node error in quantum Monte Carlo: The case of the water molecule. AB - All-electron Fixed-node DiffusionMonte Carlo calculations for the nonrelativistic ground-state energy of the water molecule at equilibrium geometry are presented. The determinantal part of the trial wavefunction is obtained from a selected Configuration Interaction calculation[Configuration Interaction using a Perturbative Selection done Iteratively (CIPSI) method] including up to about 1.4 * 10(6) of determinants. Calculations are made using the cc-pCVnZ family of basis sets, with n = 2 to 5. In contrast with most quantum Monte Carlo works no re optimization of the determinantal part in presence of a Jastrow is performed. For the largest cc-pCV5Z basis set the lowest upper bound for the ground-state energy reported so far of -76.437 44(18) is obtained. The fixed-node energy is found to decrease regularly as a function of the cardinal numbern and the Complete Basis Set limit associated with exact nodes is easily extracted. The resulting energy of -76.438 94(12) - in perfect agreement with the best experimentally derived value - is the most accurate theoretical estimate reported so far. We emphasize that employing selected configuration interactionnodes of increasing quality in a given family of basis sets may represent a simple, deterministic, reproducible, and systematic way of controlling the fixed-node error in diffusionMonte Carlo. PMID- 27389202 TI - Communication: Influence of nanophase segregation on ion transport in room temperature ionic liquids. AB - We report measurements of the ionic conductivity, shear viscosity, and structural dynamics in a homologous series of quaternary ammonium ionic liquids (ILs) and a prototypical imidazolium-based IL over a wide range of temperatures down to the glass transition. We find that the ionic conductivity of these materials generally decreases, while the shear viscosity correspondingly increases, with increasing volume fraction of aliphatic side groups. Upon crossing an aliphatic volume fraction of ~0.40, we observe a sharp, order-of-magnitude decrease in ionic conductivity and enhancement of viscosity, which coincides with the presence of long-lived, nanometer-sized alkyl aggregates. These strong changes in dynamics are not mirrored in the ionicity of these ILs, which decreases nearly linearly with aliphatic volume fraction. Our results demonstrate that nanophase segregation in neat ILs strongly reduces ionic conductivity primarily due to an aggregation-induced suppression of dynamics. PMID- 27389203 TI - Bayesian calibration of coarse-grained forces: Efficiently addressing transferability. AB - Generating and calibrating forces that are transferable across a range of state points remains a challenging task in coarse-grained (CG) molecular dynamics. In this work, we present a coarse-graining workflow, inspired by ideas from uncertainty quantification and numerical analysis, to address this problem. The key idea behind our approach is to introduce a Bayesian correction algorithm that uses functional derivatives of CG simulations to rapidly and inexpensively recalibrate initial estimates f0 of forces anchored by standard methods such as force-matching. Taking density-temperature relationships as a running example, we demonstrate that this algorithm, in concert with various interpolation schemes, can be used to efficiently compute physically reasonable force curves on a fine grid of state-points. Importantly, we show that our workflow is robust to several choices available to the modeler, including the interpolation schemes and tools used to construct f0. In a related vein, we also demonstrate that our approach can speed up coarse-graining by reducing the number of atomistic simulations needed as inputs to standard methods for generating CG forces. PMID- 27389204 TI - Theory of optical transitions in pi-conjugated macrocycles. AB - We describe a theoretical and computational investigation of the optical properties of pi-conjugated macrocycles. Since the low-energy excitations of these systems are Frenkel excitons that couple to high-frequency dispersionless phonons, we employ the quantized Frenkel-Holstein model and solve it via the density matrix renormalization group (DMRG) method. First we consider optical emission from perfectly circular systems. Owing to optical selection rules, such systems radiate via two mechanisms: (i) within the Condon approximation, by thermally induced emission from the optically allowed j = +/- 1 states and (ii) beyond the Condon approximation, by emission from the j = 0 state via coupling with a totally non-symmetric phonon (namely, the Herzberg-Teller effect). Using perturbation theory, we derive an expression for the Herzberg-Teller correction and show via DMRG calculations that this expression soon fails as h omega/J and the size of the macrocycle increase. Next, we consider the role of broken symmetry caused by torsional disorder. In this case the quantum number j no longer labels eigenstates of angular momentum, but instead labels localized local exciton groundstates (LEGSs) or quasi-extended states (QEESs). As for linear polymers, LEGSs define chromophores, with the higher energy QEESs being extended over numerous LEGSs. Within the Condon approximation (i.e., neglecting the Herzberg-Teller correction) we show that increased disorder increases the emissive optical intensity, because all the LEGSs are optically active. We next consider the combined role of broken symmetry and curvature, by explicitly evaluating the Herzberg-Teller correction in disordered systems via the DMRG method. The Herzberg-Teller correction is most evident in the emission intensity ratio, I00/I01. In the Condon approximation I00/I01 is a constant function of curvature, whereas in practice it vanishes for closed rings and only approaches a constant in the limit of vanishing curvature. We calculate the optical spectra of a model system, cyclo-poly(para-phenylene ethynylene), for different amounts of torsional disorder within and beyond the Condon approximation. We show how broken symmetry and the Herzberg-Teller effect explain the spectral features. The Herzberg-Teller correction to the 0-1 emission vibronic peak is always significant. Finally, we note the qualitative similarities between the optical properties of conformationally disordered linear polymers and macrocycles in the limit of sufficiently large disorder, because in both cases they are determined by the optical properties of curved chromophores. PMID- 27389205 TI - On the inclusion of the diagonal Born-Oppenheimer correction in surface hopping methods. AB - The diagonal Born-Oppenheimer correction (DBOC) stems from the diagonal second derivative coupling term in the adiabatic representation, and it can have an arbitrary large magnitude when a gap between neighbouring Born-Oppenheimer (BO) potential energy surfaces (PESs) is closing. Nevertheless, DBOC is typically neglected in mixed quantum-classical methods of simulating nonadiabaticdynamics (e.g., fewest-switch surface hopping (FSSH) method). A straightforward addition of DBOC to BO PESs in the FSSH method, FSSH+D, has been shown to lead to numerically much inferior results for models containing conical intersections. More sophisticated variation of the DBOC inclusion, phase-space surface-hopping (PSSH) was more successful than FSSH+D but on model problems without conical intersections. This work comprehensively assesses the role of DBOC in nonadiabaticdynamics of two electronic state problems and the performance of FSSH, FSSH+D, and PSSH methods in variety of one- and two-dimensional models. Our results show that the inclusion of DBOC can enhance the accuracy of surface hopping simulations when two conditions are simultaneously satisfied: (1) nuclei have kinetic energy lower than DBOC and (2) PESs are not strongly nonadiabatically coupled. The inclusion of DBOC is detrimental in situations where its energy scale becomes very high or even diverges, because in these regions PESs are also very strongly coupled. In this case, the true quantum formalism heavily relies on an interplay between diagonal and off-diagonal nonadiabatic couplings while surface hopping approaches treat diagonal terms as PESs and off-diagonal ones stochastically. PMID- 27389206 TI - Nonequilibrium solvent effects in Born-Oppenheimer molecular dynamics for ground and excited electronic states. AB - The effects of solvent on molecular processes such as excited state relaxation and photochemical reaction often occurs in a nonequilibrium regime. Dynamic processes such as these can be simulated using excited statemolecular dynamics. In this work, we describe methods of simulating nonequilibrium solvent effects in excited statemolecular dynamics using linear-response time-dependent density functional theory and apparent surface charge methods. These developments include a propagation method for solvent degrees of freedom and analytical energy gradients for the calculation of forces. Molecular dynamics of acetaldehyde in water or acetonitrile are demonstrated where the solute-solvent system is out of equilibrium due to photoexcitation and emission. PMID- 27389207 TI - Equation-of-motion coupled cluster method for the description of the high spin excited states. AB - The equation-of-motion (EOM) coupled cluster (CC) approach in the version applicable for the excitation energy(EE) calculations has been formulated for high spin components. The EE-EOM-CC scheme based on the restricted Hartree-Fock reference and standard amplitude equations as used in the Davidson diagonalization procedure yields the singlet states. The triplet and higher spin components require separate amplitude equations. In the case of quintets, the relevant equations are much simpler and easier to solve. Out of 26 diagrammatic terms contributing to the R1 and R2 singlet equations in the case of quintets, only R2 operator survives with 5 diagrammatic terms present. In addition all terms engaging three body elements of the similarity transformed Hamiltonian disappear. This indicates a substantial simplification of the theory. The implemented method has been applied to the pilot study of the excited states of the C2 molecule and quintet states of C and Si atoms. PMID- 27389208 TI - On the accuracy of the Pade-resummed master equation approach to dissipative quantum dynamics. AB - Well-defined criteria are proposed for assessing the accuracy of quantum master equations whose memory functions are approximated by Pade resummation of the first two moments in the electronic coupling. These criteria partition the parameter space into distinct levels of expected accuracy, ranging from quantitatively accurate regimes to regions of parameter space where the approach is not expected to be applicable. Extensive comparison of Pade-resummed master equations with numerically exact results in the context of the spin-boson model demonstrates that the proposed criteria correctly demarcate the regions of parameter space where the Pade approximation is reliable. The applicability analysis we present is not confined to the specifics of the Hamiltonian under consideration and should provide guidelines for other classes of resummation techniques. PMID- 27389210 TI - Mixed semiclassical-classical propagators for the Wigner phase space representation. AB - We formulate mixed semiclassical-classical (SC-Cl) propagators by adding a further approximation to the phase-space SC propagators, which have been formulated in our previous paper [S. Koda, J. Chem. Phys. 143, 244110 (2015)]. We first show that the stationary phase approximation over the operation of the phase-space van Vleck propagator on initial distribution functions results in the classical mechanical time propagation. Then, after dividing the degrees of freedom (DOFs) of the total system into the semiclassical DOFs and the classical DOFs, the SC-Cl van Vleck propagator and the SC-Cl Herman-Kluk (HK) propagator are derived by performing the stationary phase approximation only with respect to the classical DOFs. These SC-Cl propagators are naturally decomposed to products of the phase-space SC propagators and the classical mechanical propagators when the system does not have any interaction between the semiclassical and the classical DOFs. In addition, we also numerically compare the original phase-space HK (full HK) propagator and the SC-Cl HK propagator in terms of accuracy and efficiency to find that the accuracy of the SC-Cl HK propagator can be comparable to that of the full HK propagator although the latter is more accurate than the former in general. On the other hand, we confirm that the convergence speed of the SC-Cl HK propagator is faster than that of the full HK propagator. The present numerical tests indicate that the SC-Cl HK propagator can be more accurate than the full HK propagator when they use a same and finite number of classical trajectories due to the balance of the accuracy and the efficiency. PMID- 27389209 TI - Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states. AB - Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments. PMID- 27389211 TI - Non-Hermitian wave packet approximation for coupled two-level systems in weak and intense fields. AB - We introduce a non-Hermitian Schrodinger-type approximation of optical Bloch equations for two-level systems. This approximation provides a complete and accurate description of the coherence and decoherence dynamics in both weak and strong laser fields at the cost of losing accuracy in the description of populations. In this approach, it is sufficient to propagate the wave function of the quantum system instead of the density matrix, providing that relaxation and dephasing are taken into account via automatically adjusted time-dependent gain and decay rates. The developed formalism is applied to the problem of scattering and absorption of electromagnetic radiation by a thin layer comprised of interacting two-level emitters. PMID- 27389212 TI - An assessment of mean-field mixed semiclassical approaches: Equilibrium populations and algorithm stability. AB - We study several recent mean-field semiclassical dynamics methods, focusing on the ability to recover detailed balance for long time (equilibrium) populations. We focus especially on Miller and Cotton's [J. Phys. Chem. A 117, 7190 (2013)] suggestion to include both zero point electronic energy and windowing on top of Ehrenfest dynamics. We investigate three regimes: harmonic surfaces with weak electronic coupling, harmonic surfaces with strong electronic coupling, and anharmonic surfaces with weak electronic coupling. In most cases, recent additions to Ehrenfest dynamics are a strong improvement upon mean-fieldtheory. However, for methods that include zero point electronic energy, we show that anharmonic potential energy surfaces often lead to numerical instabilities, as caused by negative populations and forces. We also show that, though the effect of negative forces can appear hidden in harmonic systems, the resulting equilibrium limits do remain dependent on any windowing and zero point energy parameters. PMID- 27389213 TI - Decomposition of the configuration-interaction coefficients in the multiconfiguration time-dependent Hartree-Fock method. AB - An approximate implementation of the multiconfiguration time-dependent Hartree Fock method is proposed, in which the matrix of configuration-interaction coefficients is decomposed into a product of matrices of smaller dimension. The applicability of this method in which all the configurations are kept in the expansion of the wave function, while the configuration-interaction coefficients are approximately calculated, is discussed by showing the results on three model systems: a one-dimensional model of a beryllium atom, a one-dimensional model of a carbon atom, and a one-dimensional model of a chain of four hydrogen atoms. The time-dependent electronic dynamics induced by a few-cycle, long-wavelength laser pulse is found to be well described at a lower computational cost compared to the standard multiconfiguration time-dependent Hartree-Fock treatment. Drawbacks of the method are also discussed. PMID- 27389214 TI - On stabilization of scattering resonances in recombination reaction that forms ozone. AB - Calculations of energy transfer in the recombination reaction that forms ozone are carried out within the framework of the mixed quantum/classical theory and using the dimensionally reduced 2D-model of ozone molecule, with bending motion neglected. Recombination rate coefficients are obtained at room temperature for symmetric and asymmetric isotopomers of singly and doubly substituted isotopologues. The processes of resonance formation, spontaneous decay, collisional dissociation, and stabilization by bath gas (Ar) are all characterized and taken into account within the steady-state approximation for kinetics. The focus is on stabilization step, where the mysterious isotopic eta effect was thought to originate from. Our results indicate no difference in cross sections for stabilization of scatteringresonances in symmetric and asymmetric isotopomers. As practical results, the general and simple analytic models for stabilization and dissociation cross sections are presented, which can be applied to resonances in any ozone molecule, symmetric or asymmetric, singly or doubly substituted. Present calculations show some isotope effect that looks similar to the experimentally observed eta-effect, and the origin of this phenomenon is in the rates of formation/decay of scatteringresonances, determined by their widths, that are somewhat larger in asymmetric isotopomers than in their symmetric analogues. However, the approximate two-dimensional model used here is insufficient for consistent and reliable description of all features of the isotopic effect in ozone. Calculations using an accurate 3D model are still needed. PMID- 27389215 TI - Revisiting the formation of cyclic clusters in liquid ethanol. AB - The liquid phase of ethanol in pure and in non-polar solvents was studied at room temperature using Fourier transform infrared (FT-IR) and (1)H nuclear magnetic resonance (NMR) spectroscopies together with theoretical approach. The FT-IR spectra for pure ethanol and solution in cyclohexane at different dilution stages are consistent with (1)H NMR results. The results from both methods were best explained by the results of the density functional theory based on a multimeric model. It is suggested that cyclic trimers and tetramers are dominated in the solution of cyclohexane/hexane with the concentration greater than 0.5M at room temperature. In liquid ethanol, while the primary components at room temperature are cyclic trimers and tetramers, there is a certain amount (~14%) of open hydroxide group representing the existence of chain like structures in the equilibria. The cyclic cluster model in the liquid and concentrated solution phase (>0.5M) can be used to explain the anomalously lower freezing point of ethanol (159 K) than that of water (273 K) at ambient conditions. In addition, (1)H NMR at various dilution stages reveals the dynamics for the formation of cyclic clusters. PMID- 27389216 TI - Electronic spectrum of 9-methylanthracenium radical cation. AB - The predissociation spectrum of the cold, argon-tagged, 9-methylanthracenium radical cation is reported from 8000 cm(-1) to 44 500 cm(-1). The reported spectrum contains bands corresponding to at least eight electronic transitions ranging from the near infrared to the ultraviolet. These electronic transitions are assigned through comparison with ab initio energies and intensities. The infrared D1<-D0 transitions exhibit significant vibronic activity, which is assigned through comparison with TD-B3LYP excited state frequencies and intensities, as well as modelled vibronic interactions. Dissociation of 9 methylanthracenium is also observed at high visible-photon energies, resulting in the loss of either CH2 or CH3. The relevance of these spectra, and the spectra of other polycyclic aromatic hydrocarbon radical cations, to the largely unassigned diffuse interstellar bands, is discussed. PMID- 27389217 TI - High spin-filter efficiency and Seebeck effect through spin-crossover iron benzene complex. AB - Electronic structures and coherent quantum transport properties are explored for spin-crossover molecule iron-benzene Fe(Bz)2 using density functional theory combined with non-equilibrium Green's function. High- and low-spin states are investigated for two different lead-molecule junctions. It is found that the asymmetrical T-shaped contact junction in the high-spin state behaves as an efficient spin filter while it has a smaller conductivity than that in the low spin state. Large spin Seebeck effect is also observed in asymmetrical T-shaped junction. Spin-polarized properties are absent in the symmetrical H-shaped junction. These findings strongly suggest that both the electronic and contact configurations play significant roles in molecular devices and metal-benzene complexes are promising materials for spintronics and thermo-spintronics. PMID- 27389218 TI - Predissociation dynamics in the 3ppiD(1)Piu (+/-)upsilon=3 and 4psigmaB(") (1)Sigmau (+)upsilon=1 states of H2 revealed by product branching ratios and fragment angular distributions. AB - The predissociation dynamics of H2+XUV->H2 (*)->H(1s)+H(2s,2p) has been studied by measuring the fragment branching ratios between the H(2s) and H(2p) states and the fragment angular distributions using the XUV (extreme ultraviolet) laser pump and UV(ultraviolet) laser probe method. The fragment angular distributions for the predissociation of the 3ppiD(1)Piu (+)upsilon=3 state show parallel transitions, demonstrating that the main components of the dissociating state have (1)Sigmau (+) symmetry. The measured fragment branching ratios, H(2s)/(H(2s) + H(2p)), for the transitions R(0), R(1), and P(2) in 3ppiD(1)Piu (+)upsilon=3< X(1)Sigmag (+)upsilon(")=0 are in good agreement with one of the previous theoretical predictions. The predissociations of the 3ppiD(1)Piu (-)(upsilon=3) state arising from the Q(1), Q(2), and Q(3) lines have also been observed. The angular distributions and the state distributions of the excited fragments (all found from the H(2p) state) illustrate that the dissociating states for the Q lines have the expected Piu (-) symmetry. The predissociation dynamics of the transition 4psigmaB("1)Sigmau (+)upsilon=1<-X(1)Sigmag (+)upsilon(")=0 was also studied. Their fragment angular distributions show the expected parallel transitions, and most of the fragments are in the H(2s) states. The Beutler-Fano profiles and the associated spectroscopic parameters for the predissociations have also been obtained by measuring the fragment yield of H(2s, 2p) as a function of excitation photon energies. PMID- 27389220 TI - The nature of the CO2 (-) radical anion in water. AB - The reductive conversion of CO2 into industrial products (e.g., oxalic acid, formic acid, methanol) can occur via aqueous CO2 (-) as a transient intermediate. While the formation, structure, and reaction pathways of this radical anion have been modelled for decades using various spectroscopic and theoretical approaches, we present here, for the first time, a vibrational spectroscopic investigation in liquid water, using pulse radiolysis time-resolved resonance Raman spectroscopy for its preparation and observation. Excitation of the radical in resonance with its 235 nm absorption displays a transient Raman band at 1298 cm(-1), attributed to the symmetric CO stretch, which is at ~45 cm(-1) higher frequency than in inert matrices. Isotopic substitution at C ((13)CO2 (-)) shifts the frequency downwards by 22 cm(-1), which confirms its origin and the assignment. A Raman band of moderate intensity compared to the stronger 1298 cm(-1) band also appears at 742 cm(-1) and is assignable to the OCO bending mode. A reasonable resonance enhancement of this mode is possible only in a bent CO2 (-)(C2v/Cs) geometry. These resonance Raman features suggest a strong solute-solvent interaction, the water molecules acting as constituents of the radical structure, rather than exerting a minor solvent perturbation. However, there is no evidence of the non equivalence (Cs) of the two CO bonds. A surprising resonance Raman feature is the lack of overtones of the symmetric CO stretch, which we interpret due to the detachment of the electron from the CO2 (-) moiety towards the solvation shell. Electron detachment occurs at the energies of 0.28 +/- 0.03 eV or higher with respect to the zero point energy of the ground electronic state. The issue of acid-base equilibrium of the radical, which has been in contention for decades, as reflected in a wide variation in the reported pKa (-0.2 to 3.9), has been resolved. A value of 3.4 +/- 0.2 measured in this work is consistent with the vibrational properties, bond structure, and charge distribution in aqueous CO2 ( ). PMID- 27389219 TI - Ultrafast excited-state deactivation of 9-methylhypoxanthine in aqueous solution: A QM/MM MD study. AB - Photoinduced ultrafast non-adiabatic decay of 9-methylhypoxanthine (9MHPX) in aqueous solution was investigated by ab initio surface-hopping dynamics calculations using a combined quantum mechanical/molecular mechanical approach. The absorption spectra of 9MHPX in aqueous solution were also explored by the hybrid cluster-continuum model at the level of time-dependent density functional theory along with the polarizable continuum model (PCM). The static electronic structure calculations indicate that the absorption spectra of 9MHPX simulated by TD-B3LYP/PCM and TD-X3LYP/PCM can reproduce very well the experimental findings, with the accuracy of about 0.20 eV. According to dynamics simulations, irradiation of 9MHPX populates the bright excited singlet S1 state, which may undergo an ultrafast non-radiative deactivation to the S0 state. The lifetime of the S1 state of 9MHPX in aqueous solution is predicted to be 115.6 fs, slightly longer than that in the gas phase (88.8 fs), suggesting that the solventwater has no significant influence on the excited-state lifetime of 9MHPX. Such a behavior in 9MHPX is distinctly different from its parent hypoxanthine keto-N9H tautomer in which the excited-state lifetime of the latter in watersolution was remarkably enhanced as compared to the gas phase. The significant difference of the photodynamical behaviors between 9MHPX and keto-N9H can be ascribed to their different hydrogen bond environment in aqueous solution. PMID- 27389221 TI - (1)H and (19)F spin-lattice relaxation and CH3 or CF3 reorientation in molecular solids containing both H and F atoms. AB - The dynamics of methyl (CH3) and fluoromethyl (CF3) groups in organic molecular (van der Waals) solids can be exploited to survey their local environments. We report solid state (1)H and (19)F spin-lattice relaxationexperiments in polycrystalline 3-trifluoromethoxycinnamic acid, along with an X-ray diffraction determination of the molecular and crystal structure, to investigate the intramolecular and intermolecular interactions that determine the properties that characterize the CF3 reorientation. The molecule is of no particular interest; it simply provides a motionless backbone (on the nuclear magnetic resonance(NMR) time scale) to investigate CF3 reorientation occurring on the NMR time scale. The effects of (19)F-(19)F and (19)F-(1)H spin-spin dipolar interactions on the complicated nonexponential NMRrelaxation provide independent inputs into determining a model for CF3 reorientation. As such, these experiments provide much more information than when only one spin species (usually (1)H) is present. In Sec. IV, which can be read immediately after the Introduction without reading the rest of the paper, we compare the barrier to CH3 and CF3 reorientation in seven organic solids and separate this barrier into intramolecular and intermolecular components. PMID- 27389222 TI - Interpretation of the vibrational energy level structure of the astructural molecular ion H5 (+) and all of its deuterated isotopomers. AB - Variational nuclear motion computations, employing an exact kinetic energy operator and two different potential energy surfaces, are performed to study the first 60 vibrational states of the molecular ion H5 (+)= [H2-H-H2](+) and all of its deuterated isotopologues and isotopomers, altogether 12 species. Detailed investigation of the vibrational wavefunctions mostly results in physically intuitive labels not only for the fundamentals but also for the overtone and combination states computed. The torsional motion associated with the left and right diatomics appears to be well separated from the other vibrational degrees of freedom for all species. The unusual structure of the higher-lying bending states and the heavy mixing of the internal motions is partly due to the astructural character of all these molecular ions. The existence of distinct isotopomers in the H5-nDn (+), n = 1-4 cases, in the energy range studied, is confirmed. Two rules determine the stability order of the isotopomers: first, when possible, H prefers to stay in the middle of the ions rather than at the sides, and, second, the isotopomer with a homonuclear diatomic at the side is always lower in energy. The large number of precise vibrational energies of the present study, as well as the detailed assignment of the states, should serve as benchmarks for future studies by more approximate nuclear-motion treatments, such as diffusion Monte Carlo and multiconfiguration time-dependent Hartree. PMID- 27389223 TI - Manganese-centered tubular boron cluster - MnB16 (-): A new class of transition metal molecules. AB - We report the observation of a manganese-centered tubular boron cluster (MnB16 ( )), which is characterized by photoelectron spectroscopy and ab initio calculations. The relatively simple pattern of the photoelectron spectrum indicates the cluster to be highly symmetric. Ab initio calculations show that MnB16 (-) has a Mn-centered tubular structure with C4v symmetry due to first order Jahn-Teller effect, while neutral MnB16 reduces to C2v symmetry due to second-order Jahn-Teller effect. In MnB16 (-), two unpaired electrons are observed, one on the Mn 3dz(2) orbital and another on the B16 tube, making it an unusual biradical. Strong covalent bonding is found between the Mn 3d orbitals and the B16 tube, which helps to stabilize the tubular structure. The current result suggests that there may exist a whole class of metal-stabilized tubular boron clusters. These metal-doped boron clusters provide a new bonding modality for transition metals, as well as a new avenue to design boron-based nanomaterials. PMID- 27389224 TI - On the applicability of one- and many-electron quantum chemistry models for hydrated electron clusters. AB - We evaluate the applicability of a hierarchy of quantum models in characterizing the binding energy of excess electrons to water clusters. In particular, we calculate the vertical detachment energy of an excess electron from water cluster anions with methods that include one-electron pseudopotential calculations, density functional theory(DFT) based calculations, and ab initio quantum chemistry using MP2 and eom-EA-CCSD levels of theory. The examined clusters range from the smallest cluster size (n = 2) up to nearly nanosize clusters with n = 1000 molecules. The examined cluster configurations are extracted from mixed quantum-classical molecular dynamics trajectories of cluster anions with n = 1000 water molecules using two different one-electron pseudopotenial models. We find that while MP2 calculations with large diffuse basis set provide a reasonable description for the hydrated electron system, DFT methods should be used with precaution and only after careful benchmarking. Strictly tested one-electron psudopotentials can still be considered as reasonable alternatives to DFT methods, especially in large systems. The results of quantum chemistry calculations performed on configurations, that represent possible excess electron binding motifs in the clusters, appear to be consistent with the results using a cavitystructure preferring one-electron pseudopotential for the hydrated electron, while they are in sharp disagreement with the structural predictions of a non-cavity model. PMID- 27389225 TI - Ring polymer molecular dynamics fast computation of rate coefficients on accurate potential energy surfaces in local configuration space: Application to the abstraction of hydrogen from methane. AB - To fast and accurately compute rate coefficients of the H/D + CH4 -> H2/HD + CH3reactions, we propose a segmented strategy for fitting suitable potential energy surface (PES), on which ring-polymer molecular dynamics (RPMD) simulations are performed. On the basis of recently developed permutation invariant polynomial neural-network approach [J. Li et al., J. Chem. Phys. 142, 204302 (2015)], PESs in local configuration spaces are constructed. In this strategy, global PES is divided into three parts, including asymptotic, intermediate, and interaction parts, along the reaction coordinate. Since less fitting parameters are involved in the local PESs, the computational efficiency for operating the PES routine is largely enhanced by a factor of ~20, comparing with that for global PES. On interaction part, the RPMD computational time for the transmission coefficient can be further efficiently reduced by cutting off the redundant part of the child trajectories. For H + CH4, good agreements among the present RPMD rates and those from previous simulations as well as experimental results are found. For D + CH4, on the other hand, qualitative agreement between present RPMD and experimental results is predicted. PMID- 27389226 TI - Elasticity of methane hydrate phases at high pressure. AB - Determination of the full elastic constants (cij) of methane hydrates (MHs) at extreme pressure-temperature environments is essential to our understanding of the elastic, thermodynamic, and mechanical properties of methane in MH reservoirs on Earth and icy satellites in the solar system. Here, we have investigated the elastic properties of singe-crystal cubic MH-sI, hexagonal MH-II, and orthorhombic MH-III phases at high pressures in a diamond anvil cell. Brillouin light scattering measurements, together with complimentary equation of state (pressure-density) results from X-ray diffraction and methane site occupancies in MH from Raman spectroscopy, were used to derive elastic constants of MH-sI, MH II, and MH-III phases at high pressures. Analysis of the elastic constants for MH sI and MH-II showed intriguing similarities and differences between the phases' compressional wave velocity anisotropy and shear wave velocity anisotropy. Our results show that these high-pressure MH phases can exhibit distinct elastic, thermodynamic, and mechanical properties at relevant environments of their respective natural reservoirs. These results provide new insight into the determination of how much methane exists in MH reservoirs on Earth and on icy satellites elsewhere in the solar system and put constraints on the pressure and temperature conditions of their environment. PMID- 27389227 TI - Effect of local structures on crystallization in deeply undercooled metallic glass-forming liquids. AB - The crystallization mechanism in deeply undercooled ZrCu metallic glass-forming liquids was investigated via molecular dynamics simulations. It was found that the crystallization process is mainly controlled by the growth of crystal nuclei formed by the BCC-like atomic clusters, consistent with experimental speculations. The crystallization rate is found to relate to the number of growing crystal nuclei in the crystallization process. The crystallization rate in systems with more crystal nuclei is significantly hindered by the larger surface fractions of crystal nuclei and their different crystalline orientations. It is further revealed that in the crystallization in deeply undercooled regions, the BCC-like crystal nuclei are formed from the inside of the precursors formed by the FCC-like atomic clusters, and growing at the expense of the precursors. Meanwhile, the precursors are expanding at the expense of the outside atomic clusters. This process is consistent with the so-called Ostwald step rule. The atomic structures of metallic glasses are found to have significant impact on the subsequent crystallization process. In the Zr85Cu15 system, the stronger spatial correlation of Cu atoms could hinder the crystallization processes in deeply undercooled regions. PMID- 27389228 TI - Sub- and super-Maxwellian evaporation of simple gases from liquid water. AB - Non-Maxwellian evaporation of light atoms and molecules (particles) such as He and H2 from liquids has been observed experimentally. In this work, we use simulations to study systematically the evaporation of Lennard-Jones particles from liquid water. We find instances of sub- and super-Maxwellian evaporation, depending on the mass of the particle and the particle-water interaction strength. The observed trends are in qualitative agreement with experiment. We interpret these trends in terms of the potential of mean force and the effectiveness and frequency of collisions during the evaporation process. The angular distribution of evaporating particles is also analyzed, and it is shown that trends in the energy from velocity components tangential and normal to the liquid surface must be understood separately in order to interpret properly the angular distributions. PMID- 27389229 TI - Contact stiffness and damping of liquid films in dynamic atomic force microscope. AB - The mechanical properties and dissipation behaviors of nanometers confined liquid films have been long-standing interests in surface force measurements. The correlation between the contact stiffness and damping of the nanoconfined film is still not well understood. We establish a novel computational framework through molecular dynamics (MD) simulation for the first time to study small-amplitude dynamic atomic force microscopy (dynamic AFM) in a simple nonpolar liquid. Through introducing a tip driven dynamics to mimic the mechanical oscillations of the dynamic AFM tip-cantilever assembly, we find that the contact stiffness and damping of the confined film exhibit distinct oscillations within 6-7 monolayer distances, and they are generally out-of-phase. For the solid-like film with integer monolayer thickness, further compression of the film before layering transition leads to higher stiffness and lower damping, while much lower stiffness and higher damping occur at non-integer monolayer distances. These two alternating mechanisms dominate the mechanical properties and dissipation behaviors of simple liquid films under cyclic elastic compression and inelastic squeeze-out. Our MD simulations provide a direct picture of correlations between the structural property, mechanical stiffness, and dissipation behavior of the nanoconfined film. PMID- 27389230 TI - Asymmetric and symmetric absorption peaks observed in infrared spectra of CO2 adsorbed on TiO2 nanotubes. AB - Infrared spectra of CO2 physisorbed on titania nanotubes (TiNTs), predominantly in the anatase polymorph, were measured at 81 K. Asymmetric and symmetric absorption peaks due to the antisymmetric stretch vibration (nu3) of CO2 were observed at 2340 cm(-1) and 2350 cm(-1), respectively. On the basis of the exposure- and time-dependence of the spectrum, the 2340 cm(-1) peak was attributed to CO2 at the defective sites related to subsurface O vacancies (Vos) while the 2350 cm(-1) peak was assigned to that at the fivefold coordinated Ti(4+) sites. It was found that the generalized Fano line shape was well fitted to the 2340 cm(-1) peak. We also observed an absorption peak at 2372 cm(-1), which was attributed to the combination band of nu3 and the external mode of CO2 at Ti(4+). PMID- 27389231 TI - Quantitative interpretation of molecular dynamics simulations for X-ray photoelectron spectroscopy of aqueous solutions. AB - Over the past decade, energy-dependent ambient pressure X-ray photoelectron spectroscopy(XPS) has emerged as a powerful analytical probe of the ion spatial distributions at the vapor (vacuum)-aqueous electrolyteinterface. These experiments are often paired with complementary molecular dynamics (MD) simulations in an attempt to provide a complete description of the liquidinterface. There is, however, no systematic protocol that permits a straightforward comparison of the two sets of results. XPS is an integrated technique that averages signals from multiple layers in a solution even at the lowest photoelectron kinetic energies routinely employed, whereas MD simulations provide a microscopic layer-by-layer description of the solution composition near the interface. Here, we use the National Institute of Standards and Technology database for the Simulation of Electron Spectra for Surface Analysis (SESSA) to quantitatively interpret atom-density profiles from MD simulations for XPS signal intensities using sodium and potassium iodide solutions as examples. We show that electron inelastic mean free paths calculated from a semi-empirical formula depend strongly on solution composition, varying by up to 30% between pure water and concentrated NaI. The XPS signal thus arises from different information depths in different solutions for a fixed photoelectron kinetic energy. XPS signal intensities are calculated using SESSA as a function of photoelectron kinetic energy (probe depth) and compared with a widely employed ad hoc method. SESSA simulations illustrate the importance of accounting for elastic-scattering events at low photoelectron kinetic energies (<300 eV) where the ad hoc method systematically underestimates the preferential enhancement of anions over cations. Finally, some technical aspects of applying SESSA to liquidinterfaces are discussed. PMID- 27389232 TI - Interfacial properties of binary mixtures of square-well molecules from Monte Carlo simulation. AB - We determine the interfacial properties of mixtures of spherical square-well molecules from direct simulation of the vapor-liquid interface. We consider mixtures with the same molecular size and intermolecular potential range but different dispersive energy parameter values. We perform Monte Carlo simulations in the canonical ensemble to obtain the interfacial properties of mixtures of square-well molecules. In particular, we determine the pressuretensor using the mechanical (virial) route and the vapor-liquid interfacial tension evaluated using the Irving-Kirkwood method. In addition to the pressuretensor and the surface tension, we also obtain density profiles, coexistence densities, and interfacial thickness as functions of pressure, at a given temperature. This work can be considered as the extension of our previous work [F. J. Martinez-Ruiz and F. J. Blas, Mol. Phys. 113, 1217 (2015)] to deal with mixtures of spherical molecules that interact through a discontinuous intermolecular potential. According to our results, the main effect of increasing the ratio between the dispersive energy parameters of the mixture, epsilon22/epsilon11, is to sharpen the vapor-liquid interface and to increase the width of the biphasic coexistence region. Particularly interesting is the presence of a relative maximum in the density profiles of the more volatile component at the interface. This maximum is related with adsorption or accumulation of these molecules at the interface, since there are stronger attractive interactions between these molecules in comparison with the rest of intermolecular interactions. Also, the interfacial thickness decreases and the surface tension increases as epsilon22/epsilon11 is larger, a direct consequence of the increasing of the cohesive energy of the system. PMID- 27389233 TI - Tuning dissociation using isoelectronically doped graphene and hexagonal boron nitride: Water and other small molecules. AB - Novel uses for 2-dimensional materials like graphene and hexagonal boron nitride (h-BN) are being frequently discovered especially for membrane and catalysis applications. Still however, a great deal remains to be understood about the interaction of environmentally and industrially relevant molecules such as water with these materials. Taking inspiration from advances in hybridising graphene and h-BN, we explore using density functional theory, the dissociation of water, hydrogen, methane, and methanol on graphene, h-BN, and their isoelectronic doped counterparts: BN dopedgraphene and C doped h-BN. We find that dopedsurfaces are considerably more reactive than their pristine counterparts and by comparing the reactivity of several small molecules, we develop a general framework for dissociative adsorption. From this a particularly attractive consequence of isoelectronic doping emerges: substrates can be doped to enhance their reactivity specifically towards either polar or non-polar adsorbates. As such, these substrates are potentially viable candidates for selective catalysts and membranes, with the implication that a range of tuneable materials can be designed. PMID- 27389234 TI - Fast equilibration protocol for million atom systems of highly entangled linear polyethylene chains. AB - Equilibrated systems of entangled polymer melts cannot be produced using direct brute force equilibration due to the slow reptationdynamics exhibited by high molecular weight chains. Instead, these dense systems are produced using computational techniques such as Monte Carlo-Molecular Dynamics hybrid algorithms, though the use of soft potentials has also shown promise mainly for coarse-grained polymeric systems. Through the use of soft-potentials, the melt can be equilibrated via molecular dynamics at intermediate and long length scales prior to switching to a Lennard-Jones potential. We will outline two different equilibration protocols, which use various degrees of information to produce the starting configurations. In one protocol, we use only the equilibrium bond angle, bond length, and target density during the construction of the simulation cell, where the information is obtained from available experimental data and extracted from the force field without performing any prior simulation. In the second protocol, we moreover utilize the equilibrium radial distribution function and dihedral angle distribution. This information can be obtained from experimental data or from a simulation of short unentangled chains. Both methods can be used to prepare equilibrated and highly entangled systems, but the second protocol is much more computationally efficient. These systems can be strictly monodisperse or optionally polydisperse depending on the starting chain distribution. Our protocols, which utilize a soft-core harmonic potential, will be applied for the first time to equilibrate a million particle system of polyethylene chains consisting of 1000 united atoms at various temperatures. Calculations of structural and entanglement properties demonstrate that this method can be used as an alternative towards the generation of entangled equilibrium structures. PMID- 27389235 TI - DFT study of the effect of fluorine atoms on the crystal structure and semiconducting properties of poly(arylene-ethynylene) derivatives. AB - The effect of fluorine substitution on the molecular structure, crystal packing, and n-type semiconducting properties of a set of poly(arylene-ethynylene) polymers based on alternating thiadiazole and phenyl units linked through ethynylene groups has been studied by means of Density Functional Theory. As a result, an enlargement in the interplanar distance between cofacial polymer chains, as well as a decrease of the electronic coupling and electron mobility is predicted. On the other hand, fluorination could facilitate electron injection into the material. A polymer containing both alkoxy pendant chains and fluorine atoms is proposed as a compromise solution between efficiency of electron injection and charge transport within the material. PMID- 27389236 TI - Structure and component dynamics in binary mixtures of poly(2 (dimethylamino)ethyl methacrylate) with water and tetrahydrofuran: A diffraction, calorimetric, and dielectric spectroscopy study. AB - We have combined X-ray diffraction, neutron diffraction with polarization analysis, small angle neutron scattering,differential scanning calorimetry, and broad band dielectric spectroscopy to investigate the structure and dynamics of binary mixtures of poly(2-(dimethylamino)ethyl methacrylate) with either water or tetrahydrofuran (THF) at different concentrations. Aqueous mixtures are characterized by a highly heterogeneous structure where water clusters coexist with an underlying nano-segregation of main chains and side groups of the polymeric matrix. THF molecules are homogeneously distributed among the polymeric nano-domains for concentrations of one THF molecule/monomer or lower. A more heterogeneous situation is found for higher THF amounts, but without evidences for solvent clusters. In THF-mixtures, we observe a remarkable reduction of the glass-transition temperature which is enhanced with increasing amount of solvent but seems to reach saturation at high THF concentrations. Adding THF markedly reduces the activation energy of the polymer beta-relaxation. The presence of THF molecules seemingly hinders a slow component of this process which is active in the dry state. The aqueous mixtures present a strikingly broad glass-transition feature, revealing a highly heterogeneous behavior in agreement with the structural study. Regarding the solvent dynamics, deep in the glassy state all data can be described by an Arrhenius temperature dependence with a rather similar activation energy. However, the values of the characteristic times are about three orders of magnitude smaller for THF than for water. Water dynamics display a crossover toward increasingly higher apparent activation energies in the region of the onset of the glass transition, supporting its interpretation as a consequence of the freezing of the structuralrelaxation of the surrounding matrix. The absence of such a crossover (at least in the wide dynamic window here accessed) in THF is attributed to the lack of cooperativity effects in the relaxation of these molecules within the polymeric matrix. PMID- 27389237 TI - Dynamic and mechanical properties of supported lipid bilayers. AB - Supported lipid bilayers (SLBs) offer an excellent model system for investigating the physico-chemical properties of the cell membrane. In this work, dynamic and mechanical properties of SLBs are explored by dissipative particle dynamics simulations for lipids with different architectures (chain length, kink, and asymmetry associated with lipid tails). It is found that the lateral diffusivity (Dx) and flip-flop rate (FF) grow with increasing temperature in both gel and liquid phases and can be described by an Arrhenius-like expression. Three regimes can be clearly identified for symmetric and asymmetric saturated lipids but only two regimes are observed for kinked lipids. Both Dx and FF grow with decreasing tail length and increasing number of kinks. The stretching (KA) and apparent bending (KB) moduli exhibit concave upward curves with temperature and the minima are attained at Tm. In general, the minima of KA and KB decrease with the chain length and increase with number of kinks. The typical relation among the bending modulus, area stretching modulus, and bilayer thickness is still followed, KB = betaKAh(2) and beta is much smaller in the gel phase. The dynamic and mechanical properties of lipids with asymmetric tails are found to situate between their symmetric counterparts. PMID- 27389238 TI - Influence of nanoparticle-ion and nanoparticle-polymer interactions on ion transport and viscoelastic properties of polymer electrolytes. AB - We use atomistic simulations to probe the ion conductivities and mechanical properties of polyethylene oxide electrolytes containing Al2O3nanoparticles. We specifically study the influence of repulsive polymer-nanoparticle and ion nanoparticle interactions and compare the results with those reported for electrolytes containing the polymorph beta-Al2O3nanoparticles. We observe that incorporating repulsive nanoparticle interactions generally results in increased ionic mobilities and decreased elastic moduli for the electrolyte. Our results indicate that both ion transport and mechanical properties are influenced by the polymer segmental dynamics in the interfacial zones of the nanoparticle in the ion-doped systems. Such effects were seen to be determined by an interplay between the nanoparticle-polymer,nanoparticle-ion, and ion-polymer interactions. In addition, such interactions were also observed to influence the number of dissociated ions and the resulting conductivities. Within the perspective of the influence of nanoparticles on the polymer relaxation times in ion-doped systems, our results in the context of viscoelastic properties were consistent with the ionic mobilities. Overall, our results serve to highlight some issues that confront the efforts to use nanoparticle dispersions to simultaneously enhance the conductivity and the mechanical strength of polymer electrolyte. PMID- 27389239 TI - Regulatory inhibition of biological tissue mineralization by calcium phosphate through post-nucleation shielding by fetuin-A. AB - In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids-at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleationtheory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system. PMID- 27389240 TI - Static and dynamic properties of large polymer melts in equilibrium. AB - We present a detailed study of the static and dynamic behaviors of long semiflexible polymer chains in a melt. Starting from previously obtained fully equilibrated high molecular weight polymer melts [G. Zhang et al., ACS Macro Lett. 3, 198 (2014)], we investigate their static and dynamic scaling behaviors as predicted by theory. We find that for semiflexible chains in a melt, results of the mean square internal distance, the probability distributions of the end-to end distance, and the chain structure factor are well described by theoretical predictions for ideal chains. We examine the motion of monomers and chains by molecular dynamics simulations using the ESPResSo++ package. The scaling predictions of the mean squared displacement of inner monomers, center of mass, and relations between them based on the Rouse and the reptation theory are verified, and related characteristic relaxation times are determined. Finally, we give evidence that the entanglement length Ne,PPA as determined by a primitive path analysis (PPA) predicts a plateau modulus,GN (0)=45(rhokBT/Ne), consistent with stresses obtained from the Green-Kubo relation. These comprehensively characterized equilibrium structures, which offer a good compromise between flexibility, small Ne, computational efficiency, and small deviations from ideality, provide ideal starting states for future non-equilibrium studies. PMID- 27389242 TI - Correction to "Bifunctional Porphyrin Catalysts for the Synthesis of Cyclic Carbonates from Epoxides and CO2: Structural Optimization and Mechanistic Study". PMID- 27389241 TI - Multi-shell model of ion-induced nucleic acid condensation. AB - We present a semi-quantitative model of condensation of short nucleic acid (NA) duplexes induced by trivalent cobalt(iii) hexammine (CoHex) ions. The model is based on partitioning of bound counterion distribution around single NA duplex into "external" and "internal" ion binding shells distinguished by the proximity to duplex helical axis. In the aggregated phase the shells overlap, which leads to significantly increased attraction of CoHex ions in these overlaps with the neighboring duplexes. The duplex aggregationfree energy is decomposed into attractive and repulsive components in such a way that they can be represented by simple analytical expressions with parameters derived from molecular dynamic simulations and numerical solutions of Poisson equation. The attractive term depends on the fractions of bound ions in the overlapping shells and affinity of CoHex to the "external" shell of nearly neutralized duplex. The repulsive components of the free energy are duplex configurational entropy loss upon the aggregation and the electrostatic repulsion of the duplexes that remains after neutralization by bound CoHex ions. The estimates of the aggregationfree energy are consistent with the experimental range of NA duplex condensation propensities, including the unusually poor condensation of RNA structures and subtle sequence effects upon DNAcondensation. The model predicts that, in contrast to DNA, RNA duplexes may condense into tighter packed aggregates with a higher degree of duplex neutralization. An appreciable CoHex mediated RNA-RNA attraction requires closer inter-duplex separation to engage CoHex ions (bound mostly in the "internal" shell of RNA) into short-range attractive interactions. The model also predicts that longer NA fragments will condense more readily than shorter ones. The ability of this model to explain experimentally observed trends in NAcondensation lends support to proposed NAcondensation picture based on the multivalent "ion binding shells." PMID- 27389243 TI - Adequate Initial Heparin Dosage for Atrial Fibrillation Ablation in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants. AB - BACKGROUND AND OBJECTIVE: During atrial fibrillation ablation, heparin is required and is guided by the activated clotting time (ACT). Differences in the ACT before ablation and adequate initial heparin dosing in patients receiving non vitamin K antagonist oral anticoagulants (NOACs) were examined. METHODS: Patients who received warfarin (control, N = 90), dabigatran etexilate (N = 90), rivaroxaban (N = 90) and apixaban (N = 90) were studied. A 100 U/kg dose of heparin was administered as a reliable control dose for warfarin, and the remaining patients were randomly administered 110, 120 or 130 U/kg of heparin in each NOAC group, followed by a continuous heparin infusion. RESULTS: Periprocedural thromboembolic and major bleeding were not observed. Minor bleeding occurred rarely without significant differences among the groups examined. Baseline ACTs were longer in the warfarin (152 +/- 16 s) and dabigatran (153 +/- 13 s) groups than in the rivaroxaban (134 +/- 13 s) and apixaban (133 +/ 20 s) groups. The initial bolus heparin dosages required to produce an ACT 15 min after the initial bolus that was identical to the control (333 +/- 32 s) were 120 U/kg (318 +/- 29 s) and 130 U/kg (339 +/- 43 s) for dabigatran, 130 U/kg (314 +/- 31 s) for rivaroxaban and 130 U/kg (317 +/- 39 s) for apixaban. The NOAC groups required significantly larger doses of total heparin than the warfarin group. CONCLUSION: The baseline ACTs differed among the three NOAC groups. The results of the comparison with warfarin (the control) indicated that dosages of 120 or 130 U/kg for dabigatran, and 130 U/kg for rivaroxaban and apixaban, were adequate initial heparin dosages. PMID- 27389244 TI - Shear wave elastography of the spleen: evaluation of spleen stiffness in healthy volunteers. AB - PURPOSE: The aim of this study was to assess the mean value of spleen stiffness measured by Shear wave elastography in healthy patients and its dependence on age, sex, and spleen dimensions, and to evaluate the repeatability of this method. METHODS: The final study group included 59 healthy volunteers without any clinical evidence of liver disease, portal hypertension, hematological disorders, and without any pathological ultrasonographic spleen findings. Each patient underwent abdominal ultrasound examination and elastography of the liver and the spleen. RESULTS: The mean value of spleen stiffness was 16.6 +/- 2.5 kPa. In the group of men (N = 25), it was 17.3 +/- 2.7 kPa, and in the group of women (N = 34), it was 16.1 +/- 2.2 kPa. The study confirmed no correlation between spleen stiffness and sex, age of patients, and spleen size. Coefficient of repeatability and correlation coefficient between the results of the first and the second measurement showed good but not ideal repeatability of the measurement results. CONCLUSION: Our outcomes may be a reference point for evaluating spleen stiffness in research on patients with various illnesses. PMID- 27389245 TI - Megalencephalic leukoencephalopathy with cysts in twelve Egyptian patients: novel mutations in MLC1 and HEPACAM and a founder effect. AB - Two genes causing megalencephalic leukoencephalopathy with subcortical cysts (MLC) have been discovered so far. Here, we identified MLC1 and HEPACAM mutations in ten and two patients, respectively. The molecular results included an unreported inframe duplication mutation (c.929_930dupCTGCTG; p.L309dup) of MLC1 and a novel missense mutation c.293G>A (p.R98H) of HEPACAM. Further, the previously reported missense (c.278C>T; p.S93L) and the deletion/insertion (c.908_918delinsGCA; p.V303Gfs*96) were found in one and 8 patients (75 %), respectively. The 8 patients carrying the p.V303Gfs*96 shared a similar haplotype suggesting a founder effect. All mutations were in the homozygous state proving the autosomal recessive mode of inheritance. The core phenotype of macrocephaly, subcortical cysts and white matter appeared homogeneous although the patients differed in the onset, clinical course, disease severity and brain imaging findings. Our study expands the spectrum of mutations in MLC1 and HEPACAM and supports the genetic and clinical heterogeneity. Further, It confirms c.908_918delinsGCA (p.V303Gfs*96) as a founder mutation among Egyptian patients. This finding will contribute to provide targeted testing for this mutation in MLC patients in our population. PMID- 27389246 TI - Altered expression and localization of synaptophysin in developing cerebellar cortex of neonatal rats due to maternal diabetes mellitus. AB - There is sufficient evidence that diabetes during pregnancy is associated with a higher risk of neurodevelopmental anomalies including learning deficits, behavioral problems and motor dysfunctions in the offspring. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles and is considered as a marker for synaptogenesis and synaptic density. This study aimed to examine the effects of maternal diabetes in pregnancy on the expression and localization of SYP in the developing rat cerebellum. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. The results revealed a significant down-regulation in the mRNA expression of SYP in the offspring born to diabetic animals at both P7 and P14 (P < 0.05 each). One week after birth, there was a significant reduction in the localization of SYP expression in the external granular (EGL) and in the molecular (ML) layers of neonates born to diabetic animals (P < 0.05 each). We also found a marked decrease in the expression of SYP in all of the cerebellar cortical layers of STZ-D group pups at P14 (P < 0.05 each). Moreover, our results revealed no significant changes in either expression or localization of SYP in insulin-treated group pups when compared with the controls (P >= 0.05 each). The present study demonstrated that maternal diabetes has adverse effects on the synaptogenesis in the offspring's cerebellum. Furthermore, the rigid maternal blood glucose control in the most cases normalized these negative impacts. PMID- 27389247 TI - Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia. AB - Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 MUmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats. PMID- 27389249 TI - Disturbance of zinc and glucose homeostasis by methyl tert-butyl ether (MTBE); evidence for type 2 diabetes. AB - 1. The prevalence of diabetes and the other metabolic disorders has noticeably increased worldwide. A causal link between increasing risk of type 2 diabetes and exposure to environmental pollutants has been reported. 2. We hypothesized that exposure to methyl tert-butyl ether (MTBE), an oxygenate additive to gasoline would hinder zinc and glucose homeostasis in rats. 3. Male Sprague-Dawley rats received MTBE in drinking water for 90 days. At the end of the treatment, pancreas and blood samples were collected for biochemical and molecular examinations. Expression of four candidate genes, including Insulin1, Insulin2, MT1A, SLC30A8 by Real-Time Quantitative PCR (Q-PCR) as well as biochemical parameters, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), copper (Cu2+) and calcium (Ca2+) levels as well as High-sensitive C-reactive protein were assessed as endpoints. 4. This study suggested that MTBE exposure can be associated with disruption in zinc homeostasis and glucose tolerance. PMID- 27389248 TI - Implementing an evidence-based computerized decision support system to improve patient care in a general hospital: the CODES study protocol for a randomized controlled trial. AB - BACKGROUND: Computerized decision support systems (CDSSs) are information technology-based software that provide health professionals with actionable, patient-specific recommendations or guidelines for disease diagnosis, treatment, and management at the point-of-care. These messages are intelligently filtered to enhance the health and clinical care of patients. CDSSs may be integrated with patient electronic health records (EHRs) and evidence-based knowledge. METHODS/DESIGN: We designed a pragmatic randomized controlled trial to evaluate the effectiveness of patient-specific, evidence-based reminders generated at the point-of-care by a multi-specialty decision support system on clinical practice and the quality of care. We will include all the patients admitted to the internal medicine department of one large general hospital. The primary outcome is the rate at which medical problems, which are detected by the decision support software and reported through the reminders, are resolved (i.e., resolution rates). Secondary outcomes are resolution rates for reminders specific to venous thromboembolism (VTE) prevention, in-hospital all causes and VTE-related mortality, and the length of hospital stay during the study period. DISCUSSION: The adoption of CDSSs is likely to increase across healthcare systems due to growing concerns about the quality of medical care and discrepancy between real and ideal practice, continuous demands for a meaningful use of health information technology, and the increasing use of and familiarity with advanced technology among new generations of physicians. The results of our study will contribute to the current understanding of the effectiveness of CDSSs in primary care and hospital settings, thereby informing future research and healthcare policy questions related to the feasibility and value of CDSS use in healthcare systems. This trial is seconded by a specialty trial randomizing patients in an oncology setting (ONCO-CODES). TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02577198?term=NCT02577198&rank=1. PMID- 27389257 TI - Complete Genome Sequences of 61 Mycobacteriophages. AB - Mycobacteriophages-viruses of mycobacteria-provide insights into viral diversity and evolution as well as numerous tools for genetic dissection of Mycobacterium tuberculosis Here we report the complete genome sequences of 61 mycobacteriophages newly isolated from environmental samples using Mycobacterium smegmatis mc(2)155 that expand our understanding of phage diversity. PMID- 27389256 TI - Impact of a youth-friendly HIV clinic: 10 years of adolescent outcomes in Port-au Prince, Haiti. AB - INTRODUCTION: Adolescents account for over 40% of new HIV infections in Haiti. This analysis compares outcomes among HIV-positive adolescents before and after implementation of an adolescent HIV clinic in Port-au-Prince, Haiti. METHODS: We conducted a cohort study using programmatic data among HIV-positive adolescents aged 13 to 19. Data from 41,218 adolescents who were HIV tested from January 2003 to December 2012 were included. Outcomes across the HIV care cascade were assessed before and after implementation of an adolescent clinic (2009), including HIV testing, enrolment in care, assessment for antiretroviral therapy (ART) eligibility, ART initiation and 12-month retention. Pre-ART outcomes were assessed 12 months after HIV testing. Factors associated with pre-ART and ART attrition were identified through multivariable competing risk and Cox proportional hazards regression modelling. RESULTS: Cumulatively, 1672 (4.1%) adolescents tested HIV positive (80% female, median age 16 years). Retention by cascade step comparing pre- and post-clinic included the following: 86% versus 87% of patients enrolled in care, 61% versus 79% were assessed for ART eligibility, 85% versus 92% initiated ART and 68% versus 66% were retained 12 months after ART initiation. Pre-ART attrition decreased from 61% pre-clinic to 50% post-clinic (p<0.001). Pre-ART attrition was associated with being female (sub-distributional hazard ratio (sHR): 1.59; CI: 1.31-1.93), syphilis diagnosis (sHR: 1.47; CI: 1.16-1.85) and slum residence (sHR: 0.84; CI: 0.72-0.97). ART attrition was associated with syphilis diagnosis (hazard ratio (HR): 2.23; CI: 1.35-3.68) and CD4 <50 cells/uL (HR: 1.88; CI: 1.15-3.06). CONCLUSIONS: Implementation of a youth-friendly adolescent clinic improved retention in HIV care among adolescents, particularly in the assessment of ART eligibility and ART initiation. Additional interventions are needed to improve retention among pre ART patients and support long-term retention among ART patients. PMID- 27389258 TI - Complete Genome Sequences of 11 Haemophilus ducreyi Isolates from Children with Cutaneous Lesions in Vanuatu and Ghana. AB - Haemophilus ducreyi causes chancroid and has recently been shown to be a significant cause of cutaneous lesions in tropical or subtropical regions where yaws is endemic. Here, we report the draft genome assemblies for 11 cutaneous strains of Haemophilus ducreyi, isolated from children in Vanuatu and Ghana. PMID- 27389259 TI - Draft Genome Sequence of the Deep-Sea Basidiomycetous Yeast Cryptococcus sp. Strain Mo29 Reveals Its Biotechnological Potential. AB - Cryptococcus sp. strain Mo29 was isolated from the Rainbow hydrothermal site on the Mid-Atlantic Ridge. Here, we present the draft genome sequence of this basidiomycetous yeast strain, which has highlighted its biotechnological potential as revealed by the presence of genes involved in the synthesis of secondary metabolites and biotechnologically important enzymes. PMID- 27389260 TI - Draft Genome Sequence of the Deep-Sea Ascomycetous Filamentous Fungus Cadophora malorum Mo12 from the Mid-Atlantic Ridge Reveals Its Biotechnological Potential. AB - Cadophora malorum Mo12 was isolated from the Rainbow hydrothermal site on the Mid Atlantic Ridge. We present the draft genome sequence of this filamentous fungal strain, which has high biotechnological potentials as revealed by the presence of genes encoding biotechnologically important enzymes and genes involved in the synthesis of secondary metabolites. PMID- 27389261 TI - Draft Genome Sequence of a Hypermucoviscous Extended-Spectrum-beta-Lactamase Producing Klebsiella quasipneumoniae subsp. similipneumoniae Clinical Isolate. AB - A clinical isolate of extended-spectrum-beta-lactamase-producing Klebsiella quasipneumoniae subsp. similipneumoniae 06-219 with hypermucoviscosity phenotypes obtained from a urine culture of an adult patient was used for whole-genome sequencing. Here, we report the draft genome sequences of this strain, consisting of 53 contigs with an ~5.6-Mb genome size and an average G+C content of 57.36%. The annotation revealed 6,622 coding DNA sequences and 77 tRNA genes. PMID- 27389262 TI - Whole-Genome Sequence of Multidrug-Resistant Pseudomonas aeruginosa Strain BAMCPA07-48, Isolated from a Combat Injury Wound. AB - We report here the complete genome sequence of Pseudomonas aeruginosa strain BAMCPA07-48, isolated from a combat injury wound. The closed genome sequence of this isolate is a valuable resource for pathogenome characterization of P. aeruginosa associated with wounds, which will aid in the development of a higher resolution phylogenomic framework for molecular-guided pathogen-surveillance. PMID- 27389263 TI - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Kiambu Strain CRJJGF_00061 (Phylum Gammaproteobacteria). AB - We report a 4.58 Mbp draft genome sequence of Salmonella enterica subsp. enterica serovar Kiambu strain CRJJGF_00061 isolated from cattle in 2004. PMID- 27389264 TI - Complete Genome Sequence of Nonagglutinating Lactococcus garvieae Strain 122061 Isolated from Yellowtail in Japan. AB - Nonagglutinating Lactococcus garvieae has been isolated from diseased farmed yellowtail in Japan since 2012. In this study, the complete genome and plasmid sequence of nonagglutinating L. garvieae strain 122061 was determined, to our knowledge, for the first time. PMID- 27389265 TI - Genome Sequence of Gordonia Phage Yvonnetastic. AB - Gordonia bacteriophage Yvonnetastic was isolated from soil in Pittsburgh, PA, using Gordonia terrae 3612 as a host. Yvonnetastic has siphoviral morphology and a genome of 98,136 bp, with 198 predicted protein-coding genes and five tRNA genes. Yvonnetastic does not share substantial sequence similarity with other sequenced bacteriophage genomes. PMID- 27389266 TI - Draft Genome Sequence of Paecilomyces hepiali, Isolated from Cordyceps sinensis. AB - Paecilomyces hepiali is an endoparasitic fungus that commonly exists in the natural Cordyceps sinensis Here, we report the draft genome sequence of P. hepiali, which will facilitate the exploitation of medicinal compounds produced by the fungus. PMID- 27389267 TI - Complete Genome Sequence of Porcine Epidemic Diarrhea Virus from an Outbreak in a Vaccinated Farm in Shandong, China. AB - Porcine epidemic diarrhea virus, a member of the family Coronaviridae, is an economically important pathogen that causes severe enteritis, vomiting, dehydration, and a high mortality rate, especially among suckling piglets. Here, we report the complete genome sequence (28,036 nucleotides [nt]) of a porcine epidemic diarrhea virus (PEDV) strain isolated in a novel outbreak in Shandong, China. PMID- 27389268 TI - Draft Genome Sequence of Burkholderia sp. Strain CCA53, Isolated from Leaf Soil. AB - Burkholderia sp. strain CCA53 was isolated from leaf soil collected in Higashi Hiroshima City in Hiroshima Prefecture, Japan. Here, we present a draft genome sequence of this strain, which consists of a total of 4 contigs containing 6,647,893 bp, with a G+C content of 67.0% and comprising 9,329 predicted coding sequences. PMID- 27389269 TI - Draft Genome Sequence of the Endophytic Strain Rhodococcus kyotonensis KB10, a Potential Biodegrading and Antibacterial Bacterium Isolated from Arabidopsis thaliana. AB - Rhodococcus kyotonensis KB10 is an endophytic bacterium isolated from Arabidopsis thaliana The organism showed mild antibacterial activity against the phytopathogen Pseudomonas syringae pv. tomato DC3000. This study reports the genome sequence of R. kyotonensis KB10. This bacterium contains an ectoine biosynthesis gene cluster and has the potential to degrade nitroaromatic compounds. The identified bacterium may be a suitable biocontrol agent and degrader of environmental pollutants. PMID- 27389270 TI - Complete Genome Sequence of a Rabies Virus Strain Isolated from a Brown Bear (Ursus arctos) in Primorsky Krai, Russia (November 2014). AB - We report here the complete genome sequence (GenBank KP997032) of rabies virus strain RABV/Ursus arctos/Russia/Primorye/PO-01/2014, isolated in November 2014 from a brown bear (Ursus arctos) that attacked a person in Primorsky Krai (Russian Federation). This strain was clustered into the Eurasian genetic subgroup of genotype 1 (street rage). PMID- 27389271 TI - Draft Genome Sequence of the Causative Antigen of Summer-Type Hypersensitivity Pneumonitis, Trichosporon domesticum JCM 9580. AB - Here, we report the draft genome sequence of Trichosporon domesticum JCM 9580, isolated from the house of a patient with summer-type hypersensitivity pneumonitis (SHP) in Japan. This genomic information will help elucidate the mechanisms of the development of SHP. PMID- 27389272 TI - Draft Genome Sequence of "Candidatus Mycoplasma haemobos," a Hemotropic Mycoplasma Identified in Cattle in Mexico. AB - We present here the draft genome sequence of the first "Candidatus Mycoplasma haemobos" strain found in cattle in Mexico. This hemotropic mycoplasma causes acute and chronic disease in animals. This genome is a starting point for studying the role of this mycoplasma in coinfections and synergistic mechanisms associated with the disease. PMID- 27389273 TI - Draft Genome Sequence of a New Zealand Rangipo Strain of Mycobacterium tuberculosis. AB - The Rangipo genotype of the Mycobacterium tuberculosis complex has been associated with a number of tuberculosis (TB) outbreaks in New Zealand. We report here the draft whole-genome sequence of a representative isolate of this strain. PMID- 27389274 TI - Whole-Genome Sequencing of Two Bartonella bacilliformis Strains. AB - Bartonella bacilliformis is the causative agent of Carrion's disease, a highly endemic human bartonellosis in Peru. We performed a whole-genome assembly of two B. bacilliformis strains isolated from the blood of infected patients in the acute phase of Carrion's disease from the Cusco and Piura regions in Peru. PMID- 27389275 TI - Permanent Draft Genome Sequence for Frankia sp. Strain EI5c, a Single-Spore Isolate of a Nitrogen-Fixing Actinobacterium, Isolated from the Root Nodules of Elaeagnus angustifolia. AB - Frankia sp. strain EI5c is a member of Frankia lineage III, which is able to reinfect plants of the Eleagnaceae, Rhamnaceae, Myricaceae, and Gymnostoma, as well as the genus Alnus Here, we report the 6.6-Mbp draft genome sequence of Frankia sp. strain EI5c with a G+C content of 72.14 % and 5,458 candidate protein encoding genes. PMID- 27389276 TI - Draft Genome Sequence for the Type Strain of Corynebacterium afermentans LCDC 88 0199T, Isolated from a Human Blood Culture. AB - A draft genome for Corynebacterium afermentans LCDC 88-0199(T) was investigated. The size of the genome was 2,345,615 bp with an observed G+C content of 64.85%. Annotation revealed 2 rRNA sequences, 54 tRNA genes, and 2,164 coding sequences. Genome coverage was 85* and consisted of 24 contigs with an N50 of 187,988 bp. PMID- 27389278 TI - Rich Variety of Three-Dimensional Nanostructures Enabled by Geometrically Constraining Star-like Block Copolymers. AB - The influence of star-like architecture on phase behavior of star-like block copolymer under cylindrical confinement differs largely from the bulk (i.e., nonconfinement). A set of intriguing self-assembled morphologies and the corresponding phase diagrams of star-like (AB)f diblock copolymers with different numbers of arms f (i.e., f = 3, 9, 15, and 21) in four scenarios (phiA = 0.3 and V0 > 0; phiA = 0.3 and V0 < 0; phiA = 0.7 and V0 > 0; and phiA = 0.7 and V0 < 0 (where phiA is the volume fraction of A block) and V0 < 0 and V0 > 0 represent that the pore wall of cylindrical confinement prefers the inner A block (i.e., A preferential) and B block (i.e., B-preferential), respectively) were for the first time scrutinized by employing the pseudospectral method of self-consistent mean-field theory. Surprisingly, a new nanoscopic phase, that is, perforated lamellae-on-cylinder (denoted PC), was observed in star-like (AB)3 diblock copolymer at phiA = 0.3 and V0 > 0. With a further increase in f, a single lamellae (denoted L1) was found to possess a larger phase region. Under the confinement of A-preferential wall (i.e., V0 < 0) at phiA = 0.3, PC phase became metastable and its free energy increased as f increased. Quite intriguingly, when phiA = 0.7 and V0 > 0, where an inverted cylinder was formed in bulk, the PC phase became stable, and its free energy decreased as f increased, suggesting the propensity to form PC phase under this condition. Moreover, in stark contrast to the phase transition of C1 -> L1 -> PC (C1, a single cylindrical microdmain) at phiA = 0.3 and V0 > 0, when subjected to the A-preferential wall (phiA = 0.7), a different phase transition sequence (i.e., C1 -> PC -> L1) was identified due to the formation of a double-layer structure. On the basis of our calculations, the influence of star-like architecture on (AB)f diblock copolymer under the imposed cylindrical confinement, particularly the shift of the phase boundaries as a function of f, was thoroughly understood. These self-assembled nanostructures may hold the promise for applications as lithographic templates for nanowires, photonic crystals, and nanotechnology. PMID- 27389277 TI - Clinical significance of mitofusin-2 and its signaling pathways in hepatocellular carcinoma. AB - BACKGROUND: The mitochondrial GTPase mitofusin-2 (MFN2) gene encodes a mitochondrial membrane protein that can induce apoptosis of hepatocellular carcinoma (HCC) via the mitochondrial apoptotic pathway, as validated in our previous research. However, little is known of the clinical significance of MFN2 expression and its signaling pathways in HCC. METHODS: MFN2 mRNA expression in tumor and adjacent non-tumor tissues from 115 patients with HCC was investigated using quantitative real-time PCR. The association of the MFN2 mRNA expression level with clinical and pathological parameters was evaluated statistically, while a comparative microarray analysis was used to identify MFN2 signaling pathways in HepG2 cells. RESULTS: MFN2 was significantly (p < 0.0001) downregulated in HCC tissues. Low MFN2 expression was significantly correlated with sex and preoperative alpha-fetoprotein (p < 0.05). Both a Kaplan-Meier survival curve and multivariate analyses showed that MFN2 was related to overall survival. A comparative gene expression microarray revealed 211 upregulated (58 %) and 153 downregulated (42 %) genes. Eighteen pathways were identified as the most significant pathways correlated with MFN2. CONCLUSIONS: Low MFN2 expression in HCC indicated a worse overall survival. Crucial signaling molecules such as PI3K-AKT, cytokine receptor, and focal adhesion may participate in MFN2-mediated signaling pathway changes in HCC. PMID- 27389280 TI - Printed paper and board food contact materials as a potential source of food contamination. AB - Food contact materials (FCM) are estimated to be the largest source of food contamination. Apart from plastics, the most commonly used FCM are made of printed paper and board. Unlike their plastic counterparts, these are not covered by a specific European regulation. Several contamination issues have raised concerns towards potential adverse health effects caused by exposure to substances migrating from printed paper and board FCM. In the current study, an inventory combining the substances which may be used in printed paper and board FCM, was created. More than 6000 unique compounds were identified, the majority (77%) considered non-evaluated in terms of potential toxicity. Based on a preliminary study of their physicochemical properties, it is estimated that most of the non-evaluated single substances have the potential to migrate into the food and become bioavailable after oral intake. Almost all are included in the FACET tool, indicating that their use in primary food packaging has been confirmed by industry. Importantly, 19 substances are also present in one of the lists with substances of concern compiled by the European Chemicals Agency (ECHA). To ensure consumer safety, the actual use of these substances in printed paper and board FCM should be investigated urgently. PMID- 27389279 TI - Increased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifier. AB - BACKGROUND: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. RESULTS: Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4 mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. CONCLUSIONS: Thus, P-MAPA immunotherapy could be considered an important therapeutic strategy for NMIBC, as well as, opens a new perspective for treatment of patients that are refractory or resistant to BCG intravesical therapy. PMID- 27389281 TI - Chemistry, manufacturing and exposure assessments to support generally recognized as safe (GRAS) determinations. AB - Identity, stability, purity, intended use levels in what foods and technical effects, and probable intake are among the key components in an assessment to support GRAS determinations. The specifications of identity of a food substance are an important component of the safety assessment as changes in the physical and chemical properties of a food substance can influence its technical effect in food and can influence its nutritional or toxicological properties of the food substance. Estimating exposure is a key determining step in the safety evaluation of a food substance. Intake assessment in GRAS determination is necessarily comprehensive based on cumulative exposure, i.e. proposed new uses plus background dietary exposure. Intake estimates for safety assurance in a GRAS determination also represent conservative overestimate of chronic exposure as they are based on 2-day average daily intake and the upper percentile (90th) intake among consumers. In contrast, in a nutrient assessment where realistic intake estimates are of interest, usual intake estimates are relied upon. It should also be noted that intake estimates for GRAS determinations are also more conservative than estimate of dietary exposure by EPA (FIFRA), where mean per capita are used to assess chronic exposure. Overall, for safety assurance, intake assessments in GRAS determinations are comprehensively cumulative and typically conservative overestimate of exposures. PMID- 27389282 TI - A contemporary Colombian skeletal reference collection: A resource for the development of population specific standards. AB - Several authors who have discussed human variability and its impact on the forensic identification of bodies pose the need for regional studies documenting the global variation of the attributes analyzed osteological characteristics that aid in establishing biological profile (sex, ancestry, biological age and height). This is primarily accomplished by studying documented human skeletal collections in order to investigate secular trends in skeletal development and aging, among others in the Colombian population. The purpose of this paper is to disclose the details of the new "Contemporary Colombian Skeletal Reference Collection" that currently comprises 600 identified skeletons of both sexes, who died between 2005 and 2008; and which contain information about their cause of death. This collection has infinite potential for research, open to the national and international community, and still has pending opportunities to address a variety of topics such as studies on osteopathology, bone trauma and taphonomic studies. PMID- 27389283 TI - Surface Tension Drives the Orientation of Crystals at the Air-Water Interface. AB - The fabrication of oriented crystalline thin films is essential for a range of applications ranging from semiconductors to optical components, sensors, and catalysis. Here we show by depositing micrometric crystal particles on a liquid interface from an aerosol phase that the surface tension of the liquid alone can drive the crystallographic orientation of initially randomly oriented particles. The X-ray diffraction patterns of the particles at the interface are identical to those of a monocrystalline sample cleaved along the {104} (CaCO3) or {111} (CaF2) face. We show how this orientation effect can be used to produce thin coatings of oriented crystals on a solid substrate. These results also have important implications for our understanding of heterogeneous crystal growth beneath amphiphile monolayers and for 2D self-assembly processes at the air-liquid interface. PMID- 27389284 TI - A case of gabapentin-induced rhabdomyolysis requiring renal replacement therapy. AB - Gabapentin is commonly used for controlling convulsions, restless pain syndrome, and pain in diabetic neuropathy. Common side effects include dizziness, somnolence, ataxia, peripheral edema, and confusion; gabapentin-induced rhabdomyolysis is rarely reported. To date, the reported cases of gabapentin induced rhabdomyolysis have been associated with patients with multiple underlying diseases and assuming multiple medicines for various reasons. In this report, we describe a case of gabapentin-induced rhabdomyolysis in a 32-year-old woman with no medical history. We also review related literature and discuss the possible mechanism and the association with other factors. This case shows that gabapentin can induce rhabdomyolysis in healthy patients and that clinicians must consider the possible association between gabapentin and rhabdomyolysis. PMID- 27389285 TI - [Not Available]. PMID- 27389286 TI - [Historical perspective of mass spectrometry in microbiology]. AB - La espectrometria de masas (EM) es una tecnica de analisis que permite caracterizar muestras midiendo las masas (estrictamente las razones masa-carga) de las moleculas componentes. Cuenta con mas de un siglo de historia y evolucion tecnologica y a lo largo de los anos ha ampliado su alcance desde los isotopos a moleculas pequenas, moleculas organicas mas complejas y, en las ultimas decadas, macromoleculas (acidos nucleicos y proteinas). La EM MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) es una variante que permite el analisis de mezclas complejas de proteinas y que se ha aplicado recientemente a la identificacion de microorganismos en cultivo, convirtiendose en una herramienta rapida y eficaz para el diagnostico microbiologico que ha conseguido entrar en poco tiempo en la rutina de muchos servicios de microbiologia clinica. El gran impacto que ha tenido esta impulsando el desarrollo de nuevas aplicaciones en el campo de la microbiologia clinica. PMID- 27389287 TI - [Application of mass spectrometry to bacterial identification]. AB - Correct and rapid identification of bacteria is essential for the correct diagnosis and treatment of infected patients. Until a few years ago, biochemical, colorimetric or even antibiotic sensitivity tests were used to identify genera and species. The main limitations of these methods were the time needed for their performance and the difficulty of distinguishing between microorganisms that were little reactive, highly similar, or difficult to culture. Many of these problems have been solved by the introduction of mass spectrometry (MS) in the laboratory with the use of MALDI-TOF (matrix-assisted laser desorption ionization time-of flight). Knowledge of the strengths and weaknesses of this technology is essential to be able to take maximum advantage of this technique. Not all microorganisms can be identified with the same ease and reliability by MALDI-TOF and microbiologists need to know how to interpret the results obtained with this technique and the available alternatives in order to identify the microorganisms causing the most problems. This article aims to summarise the available information on the correct identification of the main human pathogenic bacteria through the use of MALDI-TOF MS, focusing on Gram-negative, Grampositive and anaerobic microorganisms. The main factors that must be taken into account for the reliable identification of any bacterium are the conditions for culture, sample preparation with the ideal extraction method and especially the use of a correct and updated database. PMID- 27389288 TI - [Use of MALDI-TOF in the rapid diagnosis of sepsis]. AB - The introduction of mass spectrometry through MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) in the diagnosis of bacteraemia and fungaemia has represented a revolution due to the rapidity and reliability of the results that it can offer to microbiology services and laboratories through analysis of the mass spectrum of the bacterial protein directly from positive blood culture bottles. These data are more useful if they are used in conjunction with other techniques able to identify the antibiotic resistance pattern of the microorganism. There is a need for a process of standardising sample processing protocols and for perfecting the identification of the agents causing bacteraemia, especially in some species of Gram-positive cocci and in polymicrobial processes. The introduction of this methodology provides rapid information that is highly important for the clinical management of bacteraemia. The availability of a multidisciplinary working group that applies all this information quickly and correctly in hospitals will improve the quality of care, reduce antibiotic expenditure and hospital stay and help to control the serious problem of antibiotic resistance. PMID- 27389289 TI - [Application of mass spectrometry in mycology]. AB - MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) is becoming an essential tool in most microbiology laboratories. At present, by using a characteristic fungal profile obtained from whole cells or through simple extraction protocols, MALDI-TOF MS allows the identification of pathogenic fungi with a high performance potential. This methodology decreases the laboratory turnaround time, optimizing the detection of mycoses. This article describes the state-of-the-art of the use of MALDI-TOF MS for the detection of human clinical fungal pathogens in the laboratory and discusses the future applications of this technology, which will further improve routine mycological diagnosis. PMID- 27389290 TI - [Application of mass spectrometry in mycobacteria]. AB - To date, more than 170 species of mycobacteria have been described, of which more than one third may be pathogenic to humans, representing a significant workload for microbiology laboratories. These species must be identified in clinical practice, which has long been a major problem due to the shortcomings of conventional (phenotypic) methods and the limitations and complexity of modern methods largely based on molecular biology techniques. The aim of this review was to briefly describe different aspects related to the use of MALDI-TOF (matrix assisted laser desorption ionization time-of-flight) mass spectrometry (MS) for the identification of mycobacteria. Several difficulties are encountered with the use of this methodology in these microorganisms mainly due to the high pathogenicity of some mycobacteria and the peculiar structure of their cell wall, requiring inactivation and special protein extraction protocols. We also analysed other relevant aspects such as culture media, the reference methods employed (gold standard) in the final identification of the different species, the cut-off used to accept data as valid, and the databases of the different mass spectrometry systems available. MS has revolutionized diagnosis in modern microbiology; however, specific improvements are needed to consolidate the use of this technology in mycobacteriology. PMID- 27389291 TI - [Rapid detection of antimicrobial resistance by MALDI-TOF mass spectrometry]. AB - In recent years, MALDI-TOF (matrix-assisted laser desorption ionization time-of flight) mass spectrometry has become established as a first-line diagnostic tool in the identification of microorganisms, including those producing human infections. Rapid detection of antimicrobial resistance is one of the future applications of this technique with the greatest likelihood of success. This review describes the most important studies published in this field and discusses potential future challenges and the clinical application of this technique in the next few years. PMID- 27389292 TI - [Studies of bacterial typing with MALDI-TOF]. AB - MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry has emerged as a potential tool for microbial characterization and identification in many microbiology departments. The technology is rapid, sensitive, and relatively inexpensive in terms of both the labour and costs involved. This review provides an overview on its utility for strain typing and epidemiological studies and explains the methodological approaches that can be used both for the performance of the technique and for the analysis of results. Finally, the review summarizes studies on the characterization of distinct bacterial species. PMID- 27389293 TI - [Studies of the cost effectiveness of MALDI-TOF and clinical impact]. AB - In general, new technologies usually increase laboratory costs due to the need for an initial investment. However, as occurred with MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry, this increase is subsequently offset by the discontinued use of traditional technologies and by the benefits to patients of the new information generated. In the clinical microbiology laboratory, the identification time is reduced with the use of MALDI TOF (by at least 24 hours) and turnaround is improved, allowing faster production of the microbiological report. This beneficial effect has mainly been studied with blood cultures in patients with bacteraemia. In these patients, the length of hospital stay has been reduced by 1.6-6.6 days, depending on the type of patient and the appropriateness of treatment. This leads to better antimicrobial use and a reduction in total hospital cost of up to 43% per patient. Another factor that has been analysed is the decrease in mortality due to better management of antimicrobial therapy. Future multicentre studies should include other factors such as hospital organisation changes and clinical activity arising in response to the efforts of the clinical microbiology laboratory to rapidly obtain information of clinical value. PMID- 27389294 TI - [Future applications of mass spectrometry in microbiology]. AB - MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) has been vigorously introduced in many clinical microbiology laboratories for the rapid and accurate identification of bacteria and fungi. In fact, the implementation of this methodology can be considered a revolution in these laboratories. In addition to microbial identification, MALDI-TOF MS is being used for the detection of some mechanisms of antibiotic resistance and for the molecular typing of bacteria. A number of current and future applications that increase the versatility of this methodology may also be mentioned. Among these are its direct application on clinical samples, the detection of toxins or specific microbial antigens, and its application in the fields of virology and parasitology. PMID- 27389295 TI - The Effect of KOH Treatment on the Chemical Structure and Electrocatalytic Activity of Reduced Graphene Oxide Materials. AB - Reduced graphene oxide (rG-O)-based materials have great potential as metal-free electrocatalysts for the oxygen reduction reaction (ORR) owing to their electrical and electrochemical properties and large surface area. Long-term durability and chemical stability of the catalysts in the presence of electrolytes such as aqueous KOH solution are important for their use in practical applications. In this study, three types of rG-O and rG-O-K (rG-O after reaction with KOH) materials were synthesized. The chemical structures, surface areas, and catalytic ORR performances of the rG-O materials were compared with those of the corresponding rG-O-K materials. The onset potentials of the rG-O materials for electrocatalytic reduction of oxygen are almost the same as those of the corresponding rG-O-K materials; however, the current density and the number of transferred electrons are significantly reduced. These data show that the catalytic ORR performance of rG-O-based materials can be altered by KOH. PMID- 27389297 TI - Reflexivity and the "Acting Subject": Conceptualizing the Unit of Analysis in Qualitative Health Research. AB - The ways in which social scientists conceptualize the "reflexive" human subject have important consequences for how we go about our research. Whether and how we understand human subjects to be the authors of our own actions helps to structure what we say about health, health care, and the many other topics addressed in qualitative health research. In this article, I critically discuss assumptions of human reflexivity that are built into qualitative social science of health and medicine. I describe three alternative ways of understanding reflexive thought and human action derived from the theoretical works of Pierre Bourdieu, Bruno Latour, and George Lakoff and Mark Johnson, respectively. I then apply these three different ways of thinking about reflexivity and the acting subject to the analysis of an excerpt of participant observation data from a health services research study of transitions from hospital to home, illuminating the different kinds of analyses that arise from each perspective. I conclude with a call for social scientists to commit to the search for better ways of understanding the human subject, resisting the temptation to "settle" on theoretical statements that close down the path to more sophisticated conceptualizations of human thought and action. PMID- 27389296 TI - Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder - A systematic review and a meta-analysis. AB - BACKGROUND: There has been a steady increase in the prescription of antidepressants for the elderly. This study comprises a systematic review of randomized, placebo-controlled trials of antidepressants for treatment of depressive disorder in people aged 65 years or more. METHODS: PubMed, EMBASE, Cochrane Library, CINAL, and PsycINFO were searched until May 2016. Where appropriate, the results were synthesized in meta-analyses. RESULTS: Twelve trials met the inclusion criteria. For patients with major depressive disorder, selective serotonin re-uptake inhibitors (SSRI) were not superior to placebo in achieving remission (OR: 0.79, 95% CI: 0.61-1.03) or response (OR=0.86, 95% CI: 0.51-1.10) after 8 weeks of treatment (three trials). However, maintenance treatment with SSRIs was superior to placebo in preventing relapse (OR: 0.22, 95% CI: 0.13-0.36; NNT=5, 95% CI: 3-6; two trials). Duloxetine was superior to placebo in achieving remission (OR: 1.78, 95% CI: 1.20-2.65; NNT=9, 95% CI: 6-20; three trials) and response (OR: 1.83, 95% CI: 1.96-4.08; two trials) in recurrent major depression after 8 weeks, but increased the risk of adverse events that can be problematic in the elderly. LIMITATIONS: The quality of evidence was generally low or moderate, emphasizing the uncertainty of the results. Study populations only partly covered the heterogeneous population of elderly with depressed mood, limiting the generalizability. CONCLUSION: The results underscore the importance of close monitoring of the effects of antidepressants in treatment of elderly patients with a depressive disorder. Methods for early detection of non responders and effective treatment options for this group are needed. PMID- 27389298 TI - Simvastatin and cerebral cavernous malformations (Re: Reinhard et al., 2016). PMID- 27389299 TI - Photodynamic therapy with 5-aminolaevulinic acid and DNA damage: unravelling roles of p53 and ABCG2. AB - OBJECTIVES: In spite of high sensitivity of A549 cells (p53(+/+) ) to lethal effects of photodynamic therapy with 5-aminolaevulinic acid (5-ALA/PDT), DNA damage was observed only in H1299 cells (p53(-/-) ), suggesting that p53 may exert a protective effect. Studies on human colon adenocarcinoma cell lines HCT 116, and their cognate knockouts for p53, were not entirely consistent with the assumption above. Exploring alternative explanations for such conflicting behaviour, we observed that expression of the ATP-binding cassette G2 (ABCG2), a regulator of cell component efflux, had important effects on PDT-generated DNA injury in PC3 cells (prostate) which are p53(-/-) and positive for ABCG2. Addition of an ABCG2 inhibitor in ABCG2 positive A549 (p53(+/+) ) and PC3 (p53(-/ ) ) cells eliminated resistance to DNA damage. MATERIALS AND METHODS: All cell lines investigated were incubated with 5-ALA and irradiated. Effects of PDT were evaluated assessing residual cell viability, cell-cycle profiles, PpIX localization, comet assay and Western blotting. Identical measurements were made in the presence of ABCG2 inhibitor, in cells expressing the transporter. RESULTS: Our data show that cell aptitude to defend its DNA from PDT-induced injury was mainly ruled by ABCG2 expression. These findings, while providing helpful information in predicting effectiveness of 5-ALA/PDT, may indicate a way to shift PDT from a palliative to a more effective approach in anti-cancer therapy. PMID- 27389300 TI - Fabrication of BSA-Green Tea Polyphenols-Chitosan Nanoparticles and Their Role in Radioprotection: A Molecular and Biochemical Approach. AB - Normal tissue damage from ionizing radiation during radiotherapy is a major concern in cancer treatment. Tea polyphenols (TPs) have been shown to reduce radiation-induced damage in multiple studies, but their pharmacological application is still limited due to poor bioavailability. The present study was aimed at to increase the TPs bioavailability by nanoformulation by using BSA as the matrix and chitosan as the external shell. Encapsulated TPs nanoparticles were spherical in size and promoted TPs stability in normal and gastrointestinal conditions without losing antioxidant activity. Oral administration of nanoparticles for 3 days prior to irradiation exposure has been shown to protect mice from hematological injuries that result in the reduction of radiation induced lethality. TPs reduce radiation-induced oxidative damage and apoptosis by restoring the redox status through the Nrf2-ERK pathway and reducing Bax expression, respectively. Regarding potency, encapsulated TPs have shown a significantly higher level of radioprotection than TPs, suggesting that TP nanoparticles can be explored as valuable radioprotective and pharmacotherapeutic agent. PMID- 27389301 TI - Early Identification and Prevention of the Spread of Ebola in High-Risk African Countries. AB - In the late summer of 2014, it became apparent that improved preparedness was needed for Ebola virus disease (Ebola) in at-risk countries surrounding the three highly affected West African countries (Guinea, Sierra Leone, and Liberia). The World Health Organization (WHO) identified 14 nearby African countries as high priority to receive technical assistance for Ebola preparedness; two additional African countries were identified at high risk for Ebola introduction because of travel and trade connections. To enhance the capacity of these countries to rapidly detect and contain Ebola, CDC established the High-Risk Countries Team (HRCT) to work with ministries of health, CDC country offices, WHO, and other international organizations. From August 2014 until the team was deactivated in May 2015, a total of 128 team members supported 15 countries in Ebola response and preparedness. In four instances during 2014, Ebola was introduced from a heavily affected country to a previously unaffected country, and CDC rapidly deployed personnel to help contain Ebola. The first introduction, in Nigeria, resulted in 20 cases and was contained within three generations of transmission; the second and third introductions, in Senegal and Mali, respectively, resulted in no further transmission; the fourth, also in Mali, resulted in seven cases and was contained within two generations of transmission. Preparedness activities included training, developing guidelines, assessing Ebola preparedness, facilitating Emergency Operations Center establishment in seven countries, and developing a standardized protocol for contact tracing. CDC's Field Epidemiology Training Program Branch also partnered with the HRCT to provide surveillance training to 188 field epidemiologists in Cote d'Ivoire, Guinea-Bissau, Mali, and Senegal to support Ebola preparedness. Imported cases of Ebola were successfully contained, and all 15 priority countries now have a stronger capacity to rapidly detect and contain Ebola.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27389302 TI - Corrigendum: Changes in soil organic carbon in croplands subjected to fertilizer management: a global meta-analysis. PMID- 27389303 TI - Exerting better control and specificity with singlet oxygen experiments in live mammalian cells. AB - Singlet molecular oxygen, O2(a1Deltag), is a Reactive Oxygen Species, ROS, that acts as a signaling and/or perturbing agent in mammalian cells, influencing processes that range from cell proliferation to cell death. Although the importance of O2(a1Deltag) in this regard is acknowledged, an understanding of the targets and mechanisms of O2(a1Deltag) action is inadequate. Thus, methods that better facilitate studies of O2(a1Deltag) in mammalian cells are highly desired. This is particularly important because, as a consequence of its chemistry in a cell, O2(a1Deltag) can spawn the generation of other ROS (e.g., the hydroxyl radical) that, in turn, can have a unique influence on cell behavior and function. Therefore, exerting better control and specificity in O2(a1Deltag) experiments ultimately reduces the number of variables in general studies to unravel the details of ROS-dependent cell dynamics. In this article, we summarize our recent efforts to produce O2(a1Deltag) with increased control and selectivity in microscope-based single-cell experiments. The topics addressed include (1) two photon excitation of a photosensitizer using a focused laser to create a spatially-localized volume of O2(a1Deltag) with sub-cellular dimensions, (2) protein-encapsulated photosensitizers that can be localized in a specific cellular domain using genetic engineering, and (3) direct excitation of dissolved oxygen in sensitizer-free experiments to selectively produce O2(a1Deltag) at the expense of other ROS. We also comment on our recent efforts to monitor O2(a1Deltag) in cells and to monitor the cell's response to O2(a1Deltag). PMID- 27389304 TI - Imaging flow cytometry for the screening of compounds that disrupt the Plasmodium falciparum digestive vacuole. AB - Malaria, despite being one of the world's oldest infectious diseases, remains difficult to eradicate because the parasite is rapidly developing resistance to frontline chemotherapies. Previous studies have shown that the parasite exhibits features resembling programmed cell death upon treatment with drugs that disrupt its digestive vacuole (DV), providing a phenotypic readout that can be detected using the imaging flow cytometer. Large compound collections can thus be screened to identify drugs that are able to disrupt the DV of the malaria parasite using this high-content high-throughput screening platform. As a proof-of-concept, 4440 compounds were screened using this platform in 4months and 254 hits (5.7% hit rate) were obtained. Additionally, 25 compounds (0.6% top hit rate) were observed to retain potent DV disruption activity that was comparable to the canonical DV disruptive drug chloroquine when tested at a ten-fold lower concentration from the original screen. This pilot study demonstrates the robustness and high throughput capability of the imaging flow cytometer and we report herein the methodology of this screening assay. PMID- 27389305 TI - Direct radiocarbon dating and genetic analyses on the purported Neanderthal mandible from the Monti Lessini (Italy). AB - Anatomically modern humans replaced Neanderthals in Europe around 40,000 years ago. The demise of the Neanderthals and the nature of the possible relationship with anatomically modern humans has captured our imagination and stimulated research for more than a century now. Recent chronological studies suggest a possible overlap between Neanderthals and anatomically modern humans of more than 5,000 years. Analyses of ancient genome sequences from both groups have shown that they interbred multiple times, including in Europe. A potential place of interbreeding is the notable Palaeolithic site of Riparo Mezzena in Northern Italy. In order to improve our understanding of prehistoric occupation at Mezzena, we analysed the human mandible and several cranial fragments from the site using radiocarbon dating, ancient DNA, ZooMS and isotope analyses. We also performed a more detailed investigation of the lithic assemblage of layer I. Surprisingly we found that the Riparo Mezzena mandible is not from a Neanderthal but belonged to an anatomically modern human. Furthermore, we found no evidence for the presence of Neanderthal remains among 11 of the 13 cranial and post cranial fragments re-investigated in this study. PMID- 27389306 TI - A Novel Procedure for Single-Incision Laparoscopic Cholecystectomy-The Teres Hanging Technique Combined with Fundus-First, Dome-Down Separation. AB - BACKGROUND: Generally, single-incision laparoscopic cholecystectomy (SILC) requires the use of articulating devices or additional trocars because of the technical difficulties caused by the lack of ergonomics. We developed a novel procedure comprising mainly two simple ideas, "the teres hanging technique combined with fundus-first, dome-down separation," which mainly uses conventional rigid laparoscopic instruments. In this study, we demonstrated our technique and retrospectively evaluated the clinical outcomes. SUBJECTS AND METHODS: Three trocars were set through a 2.0-cm transumbilical minilaparotomy that was covered with an EZ AccessTM combined with a lap protector. To create an adequate surgical field, the teres ligament was laparoscopically hung up with a suture on a straight needle. The gall bladder was then dissected through the fundus to the neck using rigid laparoscopic instruments without any additional trocars. At our institution, 18 consecutive patients underwent SILC using our technique from January 2014 to August 2015. Each patient had a symptomatic gallbladder (GB) stone or polyp. All operations were performed by surgeons who had never performed SILC until this study. RESULTS: In all operations, our technique was successfully completed without GB perforation or other intraoperative complications. Additional trocars or open laparotomy were not required. The median operation time was 79 minutes, and blood loss was negligible. No postoperative complications were encountered. CONCLUSIONS: Our novel procedure is safe and feasible. Even for surgeons who have never performed SILC before, our technique may become a standard for benign GB disease without requiring the use of articulating devices or additional trocars. PMID- 27389307 TI - Targeting cancer stem-like cells in glioblastoma and colorectal cancer through metabolic pathways. AB - Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC. PMID- 27389308 TI - Reforming the Otolaryngology-Head and Neck Surgery Match: Should We Embrace a Consortia Match? PMID- 27389309 TI - Spatial k-dispersion engineering of spoof surface plasmon polaritons for customized absorption. AB - Absorption of electromagnetic waves in a medium is generally manipulated by controlling the frequency dispersion of constitutive parameters. However, it is still challenging to gain the desired constitutive parameters for customized absorption over a broad frequency range. Here, by virtue of spoof surface plasmonic polaritons (SPPs), we demonstrate capabilities of the spatial k dispersion engineering for producing the customized broadband absorption. Incident waves can be efficiently converted to the spoof SPPs by plasmonic arrays, and their propagation and/or absorption can be controlled by engineering the spatial dispersion of k-vector. Based on this feature, we show how such concept is employed to achieve broadband as well as frequency-selective broadband absorptions as examples. It is expected that the proposed concept can be extended to other manipulations of propagating electromagnetic waves over a broad frequency range. PMID- 27389310 TI - Unidirectional light scattering with high efficiency at optical frequencies based on low-loss dielectric nanoantennas. AB - Dielectric nanoparticles offer low optical losses and access to both electric and magnetic Mie resonances. This enables unidirectional scattering along the incident axis of light, owing to the interference between these two resonances. Here we theoretically and experimentally demonstrate that an asymmetric dimer of dielectric nanoparticles can provide unidirectional forward scattering with high efficiency. Theoretical analyses reveal that the dimer configuration can satisfy the first Kerker condition at the resonant peaks of electric and magnetic dipolar modes, therefore showing highly efficient directional forward scattering. The unidirectional forward scattering with high efficiency is confirmed in our experiments using a silicon nanodisk dimer on a transparent substrate. This study will boost the realization of practical applications using low-loss and efficient subwavelength all-dielectric nanoantennas. PMID- 27389311 TI - Corrected QT interval anomalies are associated with worse prognosis among patients suffering from sepsis. AB - BACKGROUND: Patients suffering from sepsis experience organ failure and metabolic derangements, with a negative impact on their prognosis and survival. Objective markers for dismal prognosis in this group of patients are sought. AIMS: To assess the potential role of corrected QT interval anomalies as surrogates for metabolic derangements leading to increased short and medium-term mortality in patients suffering from sepsis. METHODS: This study utilised a historic-cohort analysis of 257 septic patients admitted to internal medicine departments. Personal data, vital signs, laboratory results and electrocardiograms were collected. Patients were grouped according to QTc duration, weather mid-range (395-490 ms) or non-mid-range, and further defined as shorter (<395 ms) or longer (>490 ms). RESULTS: Mortality rates differed significantly between the mid-range QTc group and the non-mid-range groups at 14 days (23.7 vs 38.2%, respectively; P = 0.014) and at 3 months (38.5 vs 59.6%, respectively; P = 0.001). In a three group analysis, the 14-day mortality was the highest in the longer QTc group and the lowest in the mid-range group compared with the shorter QTc group (44.4, 23.7 and 35.5%, respectively; P = 0.034), and this difference also remained at 3 months (74.1, 38.5 and 53.2%, respectively; P = 0.001). All differences remained statistically significant in a multivariate Cox regression analysis. CONCLUSIONS: QTc duration anomalies are associated with worse short- and medium-term prognosis and may act as a marker for more severe clinical sequelae. PMID- 27389312 TI - Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous beta-carboline norharman: evidence for a novel detoxification pathway. AB - Nicotinamide N-methyltransferase (NNMT) is responsible for the N-methylation of nicotinamide to 1-methylnicotinamide. Our recent studies have demonstrated that NNMT regulates cellular processes fundamental to the correct functioning and survival of the cell. It has been proposed that NNMT may possess beta-carboline (BC) N-methyltransferase activity, endogenously and exogenously produced pyridine containing compounds which, when N-methylated, are potent inhibitors of Complex I and have been proposed to have a role in the pathogenesis of Parkinson's disease. We have investigated the ability of recombinant NNMT to N-methylate norharman (NH) to 2-N-methylnorharman (MeNH). In addition, we have investigated the toxicity of the BC NH, its precursor 1,2,3,4-tetrahydronorharman (THNH) and its N methylated metabolite MeNH, using our in vitro SH-SY5Y NNMT expression model. Recombinant NNMT demonstrated NH 2N-methyltransferase activity, with a Km of 90 +/- 20 uM, a kcat of 3 * 10(-4) +/- 2 * 10(-5) s(-1) and a specificity constant (kcat/Km) of 3 +/- 1 s(-1) M(-1) THNH was the least toxic of all three compounds investigated, whereas NH demonstrated the greatest, with no difference observed in terms of cell viability and cell death between NNMT-expressing and non expressing cells. In NNMT-expressing cells, MeNH increased cell viability and cellular ATP concentration in a dose-dependent manner after 72 and 120 h incubation, an effect that was not observed after 24 h incubation or in non-NNNT expressing cells at any time point. Taken together, these results suggest that NNMT may be a detoxification pathway for BCs such as NH. PMID- 27389315 TI - Fischer-Tropsch synthesis over MOF-supported cobalt catalysts (Co@MIL-53(Al)). AB - Novel nanohybrid materials were prepared by immobilizing Co nanoparticles on a microporous framework MIL-53(Al) as a porous host matrix. The synthesized cobalt containing materials were characterized by XRD, STEM, and oxygen titration. The catalytic performance of Co@MIL-53(Al) nanohybrids was examined in Fischer Tropsch synthesis (FTS) for the first time. A higher selectivity to C5+ hydrocarbons and lower selectivity to methane for Co@MIL-53(Al) as compared to conventional Co/Al2O3 were observed. PMID- 27389313 TI - Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. AB - Immunohistochemistry of the PD-L1 protein may be predictive for anti-PD-1 and anti-PD-L1 immunotherapy in pulmonary adenocarcinoma and in clinically unselected cohorts of so-called non-small-cell lung cancer. Several PD-L1 immunohistochemistry assays with custom reagents and scoring-criteria are developed in parallel. Biomarker testing and clinical decision making would profit from harmonized PD-L1 diagnostics. To assess interobserver concordance and PD-L1 immunohistochemistry staining patterns, 15 pulmonary carcinoma resection specimens (adenocarcinoma: n=11, squamous-cell carcinoma: n=4) were centrally stained with the assays 28-8, 22C3, SP142, and SP263 according to clinical trial protocols. The slides were evaluated independently by nine pathologists. Proportions of PD-L1-positive carcinoma cells and immune cells were scored according to a 6-step system that integrates the criteria employed by the four PD L1 immunohistochemistry assays. Proportion scoring of PD-L1-positive carcinoma cells showed moderate interobserver concordance coefficients for the 6-step scoring system (Light's kappa=0.47-0.50). The integrated dichotomous proportion cut-offs (>=1, >=5, >=10, >=50%) showed good concordance coefficients (kappa=0.6 0.8). Proportion scoring of PD-L1-positive immune cells yielded low interobserver concordance coefficients both for the 6-step-score (kappa<0.2) and the dichotomous cut-offs (kappa=0.12-0.25). The assays 28-8 and 22C3 stained similar proportions of carcinoma cells in 12 of 15 cases. SP142 stained fewer carcinoma cells compared to 28-8, 22C3, and SP263 in four cases, whereas SP263 stained more carcinoma cells in nine cases. SP142 and SP263 stained immune cells more intensely. The data indicate that carcinoma cells can be reproducibly scored in PD-L1 immunohistochemistry for pulmonary adenocarcinoma and squamous-cell carcinoma. No differences in interobserver concordance were noticed among the tested assays. The scoring of immune cells yielded low concordance rates and might require specific standardization. The four tested PD-L1 assays did not show comparable staining patterns in all cases. Thus, studies that correlate staining patterns and response to immunotherapy are required to test the significance of the observed differences. PMID- 27389314 TI - Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance. AB - The diagnosis of myelodysplastic syndrome (MDS) can be challenging, and may be facilitated by correlation with cytogenetic testing. Microarray analysis using comparative genomic hybridization and/or single-nucleotide polymorphism array can detect chromosomal abnormalities not seen by standard metaphase cytogenetics. We examined the ability of combined comparative genomic hybridization and single nucleotide polymorphism analysis (hereafter referred to as 'combined array') to detect changes among 83 patients with unexplained cytopenias undergoing pathologic evaluation for MDS and compared results with 18 normal bone marrow controls. Thirty-seven patients (45%) were diagnosed with MDS, 12 patients (14%) were demonstrated to have 'indeterminate dyspoiesis' (insufficient for classification of MDS), 27 (33%) were essentially normal, and 7 patients (8%) had alternative pathologic diagnoses. Twenty-one MDS patients (57% of diagnoses) had effectively normal metaphase cytogenetics, but combined array showed that 5 of these (13% of MDS patients) harbored major cryptic chromosomal aberrations. Furthermore, nearly half of patients with 'indeterminate dyspoiesis' and 1 with normal morphology had clonal cytopenia(s) of undetermined significance by combined array analysis. Cryptic array findings among MDS patients and those with clonal cytopenias(s) included large-scale copy-neutral loss of heterozygosity (up to 118 Mb) and genomic deletion of loci implicated in MDS pathogenesis (eg, TET2 (4q22) and NUP98 (11p15)). By comparison, in MDS patients with abnormal metaphase cytogenetics, microarray mostly recapitulated findings seen by routine karyotype. Combined array analysis has considerable diagnostic yield in detecting cryptic chromosomal aberrations in MDS and in demonstrating aberrant clonal hematopoiesis in cytopenic patients with indeterminate morphologic dysplasia. PMID- 27389316 TI - Insertion of an Edwards Sapien 3 prosthesis as a mitral valve in valve implantation via a transapical approach. AB - We report a case of transapical mitral valve-in-valve implantation for a deteriorated bioprosthesis using the Edwards Sapien 3 prosthesis via the transapical approach. This case demonstrates the safety and feasibility of using the Edwards Sapien 3 prosthesis in treating degenerated bioprosthetic mitral valves. PMID- 27389317 TI - Differences in the anthropometry of Asian children and its role in metabolic health in later life: A narrative review. AB - BACKGROUND: The increasing incidence of childhood obesity in Asia could be a reflection of early life programming in which environmental/nutritional challenges during pregnancy and first two years of life (the so-called first 1000 days) influence later health. OBJECTIVE OF NARRATIVE REVIEW: To assess differences/similarities of anthropometric measures in early life and their influences on metabolic health risk in later life among children in Asia. METHODS: Literature search for publication in English using selected key words from Medline (PubMed), Scopus, Science Direct and Google Scholar published from 1994 to October 2014. Some comparisons with Caucasian setting were made when relevant. RESULTS: From 152 publications selected for this narrative review, differences in foetal growth and birth weight were deducted between Asian and Caucasian children. Infants in India and Hong Kong had increased fat mass at birth and early infancy as compared to those from other parts of the world. Pre- and during pregnancy conditions influenced birth weight; feeding practices and gender influenced post-natal growth and body composition development. High and low birth weights followed by rapid postnatal growth were linked to increased risks of obesity, insulin resistance and high blood pressure in later life. CONCLUSION: Foetal and postnatal growth trajectories are different between countries within and outside Asia. Extremes in birth weight followed by rapid postnatal growth were linked to increased risks of metabolic health of children in this region. As there is limited evidence in Asia, it is important to conduct thorough investigations by using longitudinal studies on early life programming. PMID- 27389318 TI - THORACIC RADIOGRAPHIC CHARACTERISTICS OF CANINE INFLUENZA VIRUS IN SIX DOGS. AB - Canine influenza virus is an emerging, highly contagious, respiratory pathogen that has not previously been radiographically described. In this retrospective case series study, we describe the thoracic radiographic appearance of confirmed canine influenza virus in six dogs. Radiographic findings varied, but included abnormal unstructured interstitial (one) and unstructured interstitial and alveolar (five) pulmonary patterns, which were distributed cranioventral (four), diffuse (one), and caudodorsal (one). The right middle (five), left cranial (five), and right cranial (four) lung lobes were most commonly affected. Additionally, mild pleural effusion was present in one dog. Intrathoracic lymphadenopathy and cranial mediastinal widening/fluid accumulation were not detected in any dog. Canine influenza virus should be considered as a differential diagnosis for canine patients with respiratory signs and a cranioventral unstructured interstitial to alveolar pulmonary pattern. PMID- 27389319 TI - Endoscopic approach to gastrointestinal bypass in malignant gastric outlet obstruction. AB - PURPOSE OF REVIEW: Malignant gastric outlet obstruction (GOO) is a debilitating complication of cancer associated with a poor prognosis. The primary aim in the management of malignant GOO is usually palliation starting with the reinstitution of luminal patency with either surgical bypass or enteral stenting. These traditional modalities, however, have important limitations. Endoscopic bypass is a novel approach to GOO and may be an ideal technique, in which a sustained bypass can be created through a minimally invasive approach. The goal of this review is to describe the technical aspects as well as the clinical data of endoscopic bypass. RECENT FINDINGS: A review of this novel technique is timely given recent developments of several accessories and techniques that allow for safer and easier endoscopic bypass including the advent of the lumen apposing stent, a specialized double-balloon enteric tube, the EUS-assisted technique, and the natural orifice transluminal surgery approach. In addition, accumulating and promising data have emerged supporting the endoscopic approach to gastric bypass. SUMMARY: Endoscopic bypass is a novel and developing field of therapeutic endoscopy with improving technique and promising clinical data. This review will help to shed light on the current status and future direction of this intricate endoscopic modality. PMID- 27389320 TI - Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: a meta-analysis of randomized controlled trials. AB - Although testosterone replacement therapy can restore serum testosterone concentrations to normal level in late-onset hypogonadism patients, whether it can improve patients' quality of life remains uncertain. Therefore, we perform a meta-analysis of randomized controlled trials on this issue. Five randomized controlled trials total 1,212 patients were included. Fixed-effect model was used to calculate the weighted mean difference of score of Aging Males' Symptom rating scale. Our result reveals that testosterone replacement therapy improves patients' health-related quality of life in terms of the decrease in the AMS total score [WMD = -2.96 (-4.21, -1.71), p < .00001] and the psychological [WMD = -0.89 (-1.41, -0.37), p = .0008], somatic [WMD = -0.89 (-1.41, -0.37), p = .0008] and sexual [WMD = -1.29 (-1.75, -0.83), p < .00001] subscale score. PMID- 27389321 TI - Functionally graded porous scaffolds made of Ti-based agglomerates. AB - Mono- and double-layer porous scaffolds were successfully fabricated using ball milled agglomerates of Ti and Ti-10Nb-3Mo alloy. For selectively controlling the level of porosity and pore size, the agglomerates were sieved into two different size fractions of 100-300MUm and 300-500MUm. Compressive mechanical properties were measured on a series of cylindrical sintered compacts with different ratios of solid core diameter to porous layer width. The graded porous scaffolds exhibited stress-strain curves typical for metallic foams with a defined plateau region after yielding. The compressive strengths and elastic moduli ranged from 300 to 700MPa and 14 to 55GPa, respectively, depending on the core diameter and the material used. The obtained properties make these materials suitable for load bearing implant applications. PMID- 27389322 TI - Pore network microarchitecture influences human cortical bone elasticity during growth and aging. AB - Cortical porosity is a major determinant of bone strength. Haversian and Volkmann's canals are'seen' as pores in 2D cross-section but fashion a dynamic network of interconnected channels in 3D, a quantifiable footprint of intracortical remodeling. Given the changes in bone remodeling across life, we hypothesized that the 3D microarchitecture of the cortical pore network influences its stiffness during growth and ageing. Cubes of cortical bone of 2 mm side-length were harvested in the distal 1/3 of the fibula in 13 growing children (mean age+/-SD: 13+/-4 yrs) and 16 adults (age: 75+/-13 yrs). The cubes were imaged using desktop micro-CT (8.14um isotropic voxel size). Pores were segmented as a solid to assess pore volume fraction, number, diameter, separation, connectivity and structure model index. Elastic coefficients were derived from measurements of ultrasonic bulk compression and shear wave velocities and apparent mass density. The pore volume fraction did not significantly differ between children and adults but originates from different microarchitectural patterns. Compared to children, adults had 42% (p=0.033) higher pore number that were more connected (Connective Density: +205%, p=0.001) with a 18% (p=0.007) lower pore separation. After accounting for the contribution of pore volume fraction, axial elasticity in traction-compression mode was significantly correlated with better connectivity in growing children and with pore separation among adults. The changes in intracortical remodeling across life alter the distribution, size and connectedness of the channels from which cortical void fraction originates. These alterations in pore network microarchitecture participate in changes in compressive and shear mechanical behavior, partly in a porosity-independent manner. The assessment of pore volume fraction (i.e., porosity) provides only a limited understanding of the role of cortical void volume fraction in its mechanical properties. PMID- 27389324 TI - Idarucizumab for Reversal of Dabigatran-Associated Anticoagulation. AB - OBJECTIVE: To review clinical data on idarucizumab for the reversal of dabigatran associated anticoagulation. DATA SOURCES: Articles for this review were identified via PubMed using the MeSH term dabigatran combined with the keyword idarucizumab Additional online searches via PubMed and Google Scholar were conducted for both prescribing and cost information. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials published between 1946 and May 2016 were included for review. Bibliographies of selected articles were also manually reviewed for relevant publications that focused on reversal strategies for dabigatran-associated anticoagulation. DATA SYNTHESIS: The safety and tolerability of idarucizumab has been evaluated in 3 phase I clinical trials. The use of idarucizumab for reversing dabigatran-associated anticoagulation is also being evaluated in the phase III RE-VERSE AD study. Interim results of the RE VERSE AD study have been published. CONCLUSIONS: Idarucizumab rapidly neutralizes the anticoagulant effect of dabigatran in healthy volunteers, in patients with life-threatening bleeding, and in patients requiring urgent surgery that cannot be delayed. These observations are largely based on laboratory assessments rather than clinical outcomes. Idarucizumab is well tolerated, and it does not appear to induce procoagulant or immunogenic adverse effects. PMID- 27389323 TI - High oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production in the rat mesenteric artery. AB - Whether high oxygen is harmful to the vascular function is unclear. The present study examined if high oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production. Rat mesenteric arteries with endothelium at 95 or 50 % oxygen were subjected to isometric force recordings, measurement of thromboxane B2 levels, determination of superoxide and peroxynitrite levels and evaluation of NADPH oxidase subunit protein expression, respectively. L-cysteine (0.01-3 mM) constricted or dilated arteries at 95 and 50 % oxygen, respectively. Thromboxane receptor antagonist SQ-29,548 (1 MUM) abolished the constriction at 95 % oxygen. L-cysteine (3 mM) increased levels of thromboxane B2 in arteries upon 95 % oxygen application. L-cysteine relaxed arteries treated with superoxide inhibitor tiron (2 mM) or NADPH oxidase inhibitor gp91ds-tat (1 MUM) irrespective of the oxygen concentration while ATP sensitive K(+) channel inhibitor glibenclamide (1 MUM) and cystathionine-gamma lyase (CSE) inhibitor DL-propargylglycine (10 mM) similarly abolished the relaxation. L-cysteine (3 mM) with 95 % oxygen augmented levels of superoxide as well as nitrotyrosine within the artery, concomitantly with enhanced membrane protein expression of NADPH oxidase subunit p47phox. The higher concentration of oxygen attenuates L-cysteine-induced vasodilation via superoxide production mediated by NADPH oxidase along with thromboxane A2 production, resulting in vasoconstriction. The increased levels of superoxide, as well as peroxynitrite, coexist with the impaired vasodilation related to ATP-sensitive K(+) channels and CSE. Higher oxygen with plasma cysteine may cause oxidative stress and vasoconstrictor prostanoid production in blood vessels. PMID- 27389325 TI - Drug Class Combination-Associated Acute Kidney Injury. AB - OBJECTIVE: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). DATA SOURCES: A search of MEDLINE and Embase databases was completed using the following terms: "risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication)." STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. DATA SYNTHESIS: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. CONCLUSIONS: Our study demonstrates a lack of well-designed studies addressing drug class combination-associated AKI. The combination of NSAIDs and diuretics with or without additional renin angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs. PMID- 27389326 TI - Erratum: Tailoring superradiance to design artificial quantum systems. PMID- 27389327 TI - The Further Direction of the Gig Healthcare System as a Major Factor of the Global Gig Economy. PMID- 27389328 TI - Posttraumatic Temporal Bone Meningocele Presenting as a Cystic Mass in the External Auditory Canal. AB - INTRODUCTION: Temporal bone meningoencephalic herniation may occur in head trauma. It is a rare condition with potentially dangerous complications. Several different routes for temporal bone meningoencephalocele have been proposed. CLINICAL REPORT: An11-year-old boy with history of head trauma initially presented with a 9-months history of progressive right-sided hearing loss and facial weakness. The other complaint was formation of a cystic mass in the right external auditory canal. The patient underwent surgery via a mini middle cranial fossa craniotomy associated with a transmastoid approach. CONCLUSION: Although presenting symptoms can be subtle, early suspicion and confirmatory imaging aid in establishing the diagnosis. The combination of computed tomography and magnetic resonance imaging will help in proper preoperative diagnosis. The operation includes transmastoid, middle cranial fossa repair, or combination of both. The multilayer closure of bony defect is very important to avoid cerebrospinal fluid leak. Clinical manifestations, diagnosis, and surgical approaches for posttraumatic meningoencephaloceles arising in the head and neck region are briefly discussed. PMID- 27389329 TI - Long-term survival of early-stage non-small cell lung cancer patients who underwent robotic procedure: a propensity score-matched study. AB - BACKGROUND: In the past decade, many researchers focused on to robot-assisted surgery. However, on long-term outcomes for patients with early-stage non-small cell lung cancer (NSCLC), whether the robotic procedure is superior to video assisted thoracic surgery (VATS) and thoracotomy is unclear. Nonetheless, in the article titled "Long-term survival based on the surgical approach to lobectomy for clinical stage I non-small cell lung cancer: comparison of robotic, video assisted thoracic surgery, and thoracotomy lobectomy" by Yang et al. that was recently published in Annals of Surgery, the authors provided convincing evidence that the robotic procedure results in similar long-term survival as compared with VATS and thoracotomy. Minimally invasive procedures typically result in shorter lengths of hospital stay, and the robotic procedure in particular results in superior lymph node assessment. MAIN BODY: Our propensity score-matched study generated high-quality data. Based on our findings, we see promise in expanding patient access to robotic lung resections. In this study, propensity score matching minimized the bias involved between groups. Nevertheless, due to its retrospective nature, bias may still exist. Currently, the concept of rapid rehabilitation is widely accepted, and it is very difficult to set up a randomized controlled trial to compare robotic, VATS, and thoracotomy procedures for the treatment of NSCLC. Therefore, to overcome this limitation and to minimize bias, the best approach is to use a registry and prospectively collected, propensity score-matched data. CONCLUSIONS: Robotic lung resections result in similar long-term survival as compared with VATS and thoracotomy. Robot assisted and VATS procedures are associated with short lengths of hospital stay, and the robotic procedure in particular results in superior lymph node assessment. Considering the alarming increase in the incidence of lung cancer in China, a nationwide database of prospectively collected data available for clinical research would be especially important. PMID- 27389330 TI - Retroperitoneal Lymph Node Dissection: Anatomical and Technical Considerations from a Cadaveric Study. AB - PURPOSE: Metastatic testis cancer in the retroperitoneum presents a technical challenge to urologists in the primary and post-chemotherapy settings. Where possible, bilateral nerve sparing retroperitoneal lymph node dissection should be performed in an effort to preserve ejaculatory function. However, this is often difficult to achieve, given the complex neurovascular anatomy. We performed what is to our knowledge the first comprehensive examination of the anatomical relationships between the sympathetic nerves of the aortic plexus and the lumbar vessels to facilitate navigation and nerve sparing during bilateral retroperitoneal lymph node dissection. MATERIALS AND METHODS: The relative anatomy of the infrarenal vasculature (lumbar vessels, right gonadal vein and inferior mesenteric artery) was investigated in 21 embalmed human cadavers. The complex relationships between these vessels and the sympathetic nerves of the aortic plexus were examined by dissection of an additional 8 fresh human cadavers. RESULTS: Analysis of the infrarenal vasculature from 21 cadavers demonstrated that the position of the right gonadal vein and the inferior mesenteric artery may be useful to locate the right superior lumbar vein and the first pair of infrarenal lumbar arteries as well as the common lumbar trunk (vein) and the second pair of infrarenal lumbar arteries, respectively. Furthermore, the lumbar splanchnic nerves supplying the aortic plexus were most often positioned anteromedial to the respective lumbar vein. CONCLUSIONS: The current study describes the complex neurovascular relationships that are crucial to performing successful nerve sparing retroperitoneal lymph node dissection. Surgical techniques are also discussed. Collectively, these results may help surgeons decrease the rate of postoperative retrograde ejaculation and/or anejaculation. PMID- 27389331 TI - Analysis of temporal evolution of quantum dot surface chemistry by surface enhanced Raman scattering. AB - Temporal evolution of surface chemistry during oxidation of silicon quantum dot (Si-QD) surfaces were probed using surface-enhanced Raman scattering (SERS). A monolayer of hydrogen and chlorine terminated plasma-synthesized Si-QDs were spin coated on silver oxide thin films. A clearly enhanced signal of surface modes, including Si-Clx and Si-Hx modes were observed from as-synthesized Si-QDs as a result of the plasmonic enhancement of the Raman signal at Si-QD/silver oxide interface. Upon oxidation, a gradual decrease of Si-Clx and Si-Hx modes, and an emergence of Si-Ox and Si-O-Hx modes have been observed. In addition, first, second and third transverse optical modes of Si-QDs were also observed in the SERS spectra, revealing information on the crystalline morphology of Si-QDs. An absence of any of the abovementioned spectral features, but only the first transverse optical mode of Si-QDs from thick Si-QD films validated that the spectral features observed from Si-QDs on silver oxide thin films are originated from the SERS effect. These results indicate that real-time SERS is a powerful diagnostic tool and a novel approach to probe the dynamic surface/interface chemistry of quantum dots, especially when they involve in oxidative, catalytic, and electrochemical surface/interface reactions. PMID- 27389332 TI - Influences of Metabolic Inhibitors and Hydrolytic Enzymes on the Adhesion of Appressoria of Pyricularia oryzae to Wax-coated Cover-glasses. AB - For discovering the components that contributed to the bonding strength of the glue substances produced by appressoria of Pyricularia oryzae on wax-coated cover glasses, the influences of metabolic inhibitors and hydrolytic enzymes were investigated. The bonding strength of appressoria was assessed by the ratio of the remaining appressoria after sonication to the appressoria formed before sonication. Remaining appressoria decreased with increasing concentrations of cerulenin, an inhibitor of lipid synthesis, but isoprothiolane and compactin showed no influence on bonding strength. Tunicamycin, an inhibitor of glycoprotein synthesis, weakened the bonding strength of appressoria, but castanospermin had no effect. Of the hydrolytic enzymes tested, protease particularly weakened the bonding strength of appressoria. On the surfaces of substrata, the appressoria's bonding strength was higher on the hydrophobic surfaces than on the hydrophilic. These results suggest that lipid components and glycoprotein were closely associated with appressoria bonding strength to the surface of wax-coated cover-glass. PMID- 27389333 TI - Reclassification of the Strains with Low G+C Contents of DNA belonging to the Genus Gluconobacter ASAI 1935 (Acetobacteraceae). AB - Three species, Gluconobacter cerinus, G. asaii, and G. frateurii are reported to show lower G+C contents than G. oxydans. Isolate 145 also showed a similar G+C content to those of the three species. We try to reclassify the three species. G. frateurii including a type strain, isolate 145, G. cerinus IFO 3262, 3263, 3269, and G. asaii IFO 3265 formed acid from D-arabitol, ribitol, and L-arabitol. DNAs from G. cerinus IFO 3262, 3263, 3269, and G. asaii IFO 3265 showed 100-53% sequence similarity with that from the type strain of G. frateurii, but showed 31 39% and 34-42% similarity with those from the type strains of G. cerinus and G. asaii, respectively. On the basis of these observations, G. cerinus IFO 3262, 3263, 3269 and G. asaii IFO 3265 were identified as G. frateurii. The type strains of G. cerinus and G. asaii formed acid from D-arabitol, but did not form acid from ribitol and L-arabitol. DNAs from the type strains of G. cerinus and G. asaii showed species-level similarity (95 and 88%) with each other. From these results, we concluded that G. asaii is conspesific and synonymous with G. cerinus. PMID- 27389334 TI - New Geometric Isomers of Oxooctadecadienoate in Copper-catalyzed Decomposition Products of Linoleate Hydroperoxide. AB - Methyl linoleate hydroperoxide produced by autoxidation was refluxed with 10(-4) M Cu-naphthenate in benzene. Two new geometrical isomers of oxooctadecadienoate (compounds I and II) were found in addition to the four known isomers. They were isolated by a Sephadex LH-20 column chromatography with chloroform-hexane (2:1) and purified by HPLC on Nucleosil (r)100-5 and Zorbax ODS columns. UV, IR, MS, and (1)H-NMR spectra were measured. The geometry of conjugated dienes were assigned from the coupling constants of the olefinic protons. Compounds I and II were identified as 13-oxo-trans-9, cis-11- and 9-oxo-cis-10, trans-12 octadecadienoate, respectively. Each of them had a cis double bond adjacent to the oxo group. The hydroperoxides of the same geometry as compounds I and II were also detected in autoxidation products. PMID- 27389335 TI - Inhibitory Effect of the Conformation of Amylose as a Function of I2 Concentration on Glucoamylase Activity. AB - In order to gain a better understanding of the adaptability of glucoamylase to the conformational change in the substrate related with the specificity of the enzyme action, the effect of the solution conformation of amylose (the substrate) as a function of the I2 concentration on enzyme activity was studied in the initial state by using amyloses with a wide range of average degree of polymerization (DP) in the presence of excess KI. The enzyme activity for the amylose oligomers in the DP range of 20 to 100 decreased monotonically with increasing I2 concentration. This inhibition of the enzyme activity is ascribed to the effect of the conformational change in amylose of the random coil or worm like chain to a helix that is induced by the binding of I3 (-) ions responsible for inclusion complexation in combination with direct effect of free I3 (-) ions. In a rapidly mixed complex system for amylose with a large DP of 1,000, however, a significant two-step form of the inhibition of enzyme activity appeared with increasing I2 concentration, corresponding to the two-step conformational change of amylose in a random coil or worm-like chain to a helix and then to a rod-like compact structure. PMID- 27389336 TI - The Incorporation and Accumulation of Supplemented Fatty Acids in Mucor hiemalis HA-30. AB - Accumulation of free unsaturated fatty acids, added individually to the medium, into cellular triacylglycerol (TG) were examined using a fungus, Mucor hiemalis HA-30, which could produce the eicosapentaenoic acid (20:5n-3)-enriched TG. Linoleic (18:2n-6), gamma-linolenic (18:3n-6), arachidonic acids (20:4n-6), and 20:5n-3 were favored for accumulation in TG and each fatty acid accumulated in TG at about 80% purity. However, docosahexaenoic acid (22:6n-3) was not efficiently accumulated in TG and its content was about 60%. Incorporation and accumulation of various fatty acids added to the cultivation medium were investigated using a model fatty acids mixture. Generally, unsaturated fatty acids were efficiently incorporated into cells more than saturated fatty acids. Fatty acids with odd numbered double bonds such as 18:3n-3, 18:3n-6, and 20:5n-3 showed the higher incorporation efficiency compared with those with even-numbered double bonds such as 18:2n-6, 20:4n-6, and 22:6n-3. On the other hand, saturated and monounsaturated fatty acids of 16:0, 18:0, and 18:1 were preferentially accumulated in microbial cells over other fatty acids. PMID- 27389337 TI - Effect of Intracellular Glutathione on Heat-induced Cell Death in the Cyanobacterium, Synechocystis PCC 6803. AB - A correlation was found between the rate of cell death induced by heat and the GSH content of Synechocystis PCC 6803: cells accumulating GSH above the control level were more tolerant to heat than the control cells, and those containing a lower concentration of GSH were more sensitive. Lethal heating caused a decrease of GSH content, and a rapid intracellular oxidation in cells containing the decreased amount of GSH. PMID- 27389338 TI - High-pressure Carbon Dioxide Effect on Kimchi Fermentation. AB - Baechu (Chinese cabbage) kimchi was treated with high-pressure carbon dioxide at 70 kg/cm(2) for 24 h. The effect of this treatment on kimchi fermentation during storage at 10 degrees C was investigated in terms of pH value, titratable acidity, lactic acid bacterial count, and sensory properties. Kimchi samples treated with pressurized CO2 had relatively a higher pH value, lower titratable acidity, and smaller lactic acid bacterial population than the untreated sample. A sensory evaluation showed that the sourness and overall acceptability of treated kimchi were better than those of the control. The color, flavor and texture were not significantly affected by the treatment. The results indicate that high-pressure CO2 treatment could be used as one of the applicable nonthermal processes for baechu kimchi preservation. PMID- 27389339 TI - Enantioselective Synthesis of Both the Enantiomers of Jasmine Ketolactone and Its Epimer. AB - The enantioselective synthesis of jasmine ketolactone 1, which was isolated as a component of Italian jasmine oil, and its epimer 2 is described. Lactones 1 and 2 were synthesized in 5 and 4 steps, respectively, by Yamaguchi's macrolactonization method from alcohol 4. PMID- 27389340 TI - Extrinsic doping of the half-Heusler compounds. AB - Controlling the p- and n-type doping is a key tool to improve the power-factor of thermoelectric materials. In the present work we provide a detailed understanding of the defect thermochemistry in half-Heusler compounds. We calculate the formation energies of intrinsic and extrinsic defects in state of the art n-type TiNiSn and p-type TiCoSb thermoelectric materials. It is shown how the incorporation of online repositories can reduce the workload in these calculations. In TiNiSn we find that Ni- and Ti-interstitial defects play a crucial role in the carrier concentration of TiNiSn. Furthermore, we find that extrinsic doping with Sb can substantially enhance the carrier concentration, in agreement with experiment. In case of TiCoSb, we find ScTi, FeCo and SnSb being possible p-type dopants. While experimental work has mainly focussed on Sn-doping of the Sb site, the present result underlines the possibility to p-dope TiCoSb on all lattice sites. PMID- 27389342 TI - Tuberculosis as a differential diagnosis in cases of persistent otorrhea refractory to standard antimicrobial treatment. PMID- 27389341 TI - Validation and factor analysis of mother-infant bonding questionnaire in pregnant and postpartum women in Japan. AB - BACKGROUND: The Mother-Infant Bonding Questionnaire (MIBQ) has been widely used to assess maternal emotional involvement with infants. Although the reliability and validity of the MIBQ in the postpartum period has been confirmed, it remains unclear whether the MIBQ is appropriate to assess maternal bonding in both pregnancy and the postpartum period over time. Our study were aimed to 1) examine the reliability and validity of the MIBQ for clinical use among pregnant and postpartum women; and 2) examine the factor structure of the items, create subscales, and confirm the stability of the MIBQ in the pregnancy and postpartum periods. METHODS: Participants (n = 751, mean age 32.1 +/- 4.4 years) completed the MIBQ and the Edinburgh Postnatal Depression Scale (EPDS) in early pregnancy (before week 25), in late pregnancy (around week 36), 5 days after delivery, and 1 month after delivery. We randomly divided participants into two sample sets. We conducted an exploratory factor analysis of the nine MIBQ items using data from one group of mothers (Group 1; n = 376) in all four periods. The factor structure derived from the exploratory factor analysis was confirmed by a confirmatory factor analysis in the second group (Group 2; n = 375) of mothers in all four periods. RESULTS: Exploratory factor analysis yielded two factors: Lack of Affection (LA) and Anger and Rejection (AR). Confirmatory factor analysis demonstrated that LA and AR factors existed for the MIBQ in all periods. Cronbach's alpha coefficients were 0.879 and 0.584, respectively. The scores for LA and AR were significantly correlated over the four time periods. Mothers with higher AR scores on the MIBQ at any of the four periods had higher scores on the EPDS. CONCLUSIONS: The MIBQ has two subscales regardless of the timing of the assessment. The MIBQ is appropriate for pregnant as well as postpartum women to assess maternal bonding toward the fetus and infant. PMID- 27389343 TI - Analysis on the Filament Structure Evolution in Reset Transition of Cu/HfO2/Pt RRAM Device. AB - The resistive switching (RS) process of resistive random access memory (RRAM) is dynamically correlated with the evolution process of conductive path or conductive filament (CF) during its breakdown (rupture) and recovery (reformation). In this study, a statistical evaluation method is developed to analyze the filament structure evolution process in the reset operation of Cu/HfO2/Pt RRAM device. This method is based on a specific functional relationship between the Weibull slopes of reset parameters' distributions and the CF resistance (R on). The CF of the Cu/HfO2/Pt device is demonstrated to be ruptured abruptly, and the CF structure of the device has completely degraded in the reset point. Since no intermediate states are generated in the abrupt reset process, it is quite favorable for the reliable and stable one-bit operation in RRAM device. Finally, on the basis of the cell-based analytical thermal dissolution model, a Monte Carlo (MC) simulation is implemented to further verify the experimental results. This work provides inspiration for RRAM reliability and performance design to put RRAM into practical application. PMID- 27389344 TI - On the Crystal Structural Control of Sputtered TiO2 Thin Films. AB - In this study, we focused on the origin on the selective deposition of rutile and anatase TiO2 thin films during the sputtering process. The observation on microstructural evolution of the TiO2 films by transmission electron microscopy revealed the coexistence of rutile and anatase TiO2 phases in the initial stage under the preferential growth conditions for the anatase TiO2; the observations further revealed that the anatase phase gradually dominated the crystal structure with increasing film thickness. These results suggest that the bombardment during the sputtering deposition did not obviously affect the TiO2 crystal structure, and this was also confirmed by off-axis magnetron sputtering experiments. We also investigated the mechanism of the effect of Sn impurity doping on the crystal structure using first-principles calculations. It is found that the formation energy of Sn-doped rutile TiO2 is lower than that of Sn-doped anatase TiO2; this suggests that the Sn-doped TiO2 favours the rutile phase. These results offer a guideline for the utilization of selective deposition of rutile and anatase TiO2 thin films in various industrial applications. PMID- 27389345 TI - Cue-independent memory impairment by reactivation-coupled interference in human declarative memory. AB - Memory is a dynamic process. While memory becomes increasingly resistant to interference after consolidation, a brief reactivation renders it unstable again. Previous studies have shown that interference, when applied upon reactivation, impairs the consolidated memory, presumably by disrupting the reconsolidation of the memory. However, attempts have failed in disrupting human declarative memory, raising a question about whether declarative memory becomes unstable upon reactivation. Here, we used a double-cue/one-target paradigm, which associated the same target with two different cues in initial memory formation. Only one cue/target association was later reactivated and treated with behavioral interference. Our results showed, for the first time, that reactivation-coupled interference caused cue-independent memory impairment that generalized to other cues associated with the memory. Critically, such memory impairment appeared immediately after interference, before the reconsolidation process was completed, suggesting that common manipulations of reactivation-coupled interference procedures might disrupt other processes in addition to the reconsolidation process in human declarative memory. PMID- 27389346 TI - Characteristics of an epidemic outbreak with a large initial infection size. AB - A deterministic model proposed in previous literatures to approximate the well known Richards model is investigated. However, the model assumption of small initial value for infection size is released in the current manuscript. Taking the advantage of the closed form of solutions, we establish the epidemic characteristics of disease transmission: the outbreak size, the peak size and the turning point for the cumulative infected cases. It is shown that the usual disease outbreak threshold condition (the basic reproduction number R0 is greater than unity) fails to fully guarantee the existence of peaking time and turning point when the initial infection size is not relatively small. The epidemic characteristics not only depend on R0 but also on another index, the net reproduction number R0*. PMID- 27389347 TI - Programming Saposin-Mediated Compensatory Metabolic Sinks for Enhanced Ubiquinone Production. AB - Microbial synthesis of ubiquinone by fermentation processes has been emerging in recent years. However, as ubiquinone is a primary metabolite that is tightly regulated by the host central metabolism, tweaking the individual pathway components could only result in a marginal improvement on the ubiquinone production. Given that ubiquinone is stored in the lipid bilayer, we hypothesized that introducing additional metabolic sink for storing ubiquinone might improve the CoQ10 production. As human lipid binding/transfer protein saposin B (hSapB) was reported to extract ubiquinone from the lipid bilayer and form the water soluble complex, hSapB was chosen to build a compensatory metabolic sink for the ubiquinone storage. As a proof-of-concept, hSapB-mediated metabolic sink systems were devised and systematically investigated in the model organism of Escherichia coli. The hSapB-mediated periplasmic sink resulted in more than 200% improvement of CoQ8 over the wild type strain. Further investigation revealed that hSapB mediated sink systems could also improve the CoQ10 production in a CoQ10 hyperproducing E. coli strain obtained by a modular pathway rewiring approach. As the design principles and the engineering strategies reported here are generalizable to other microbes, compensatory sink systems will be a method of significant interest to the synthetic biology community. PMID- 27389348 TI - Weight Gain Effects of Second-Generation Antipsychotic Treatment in Autism Spectrum Disorder. AB - OBJECTIVE: Irritability (aggression, self-injury, and severe tantrums) associated with autism spectrum disorder (ASD) is often treated with second-generation antipsychotics (SGAs), which are well known for their associated risk of weight gain in youth. Recent reports suggest that youth with ASD treated with SGAs may suffer more pronounced weight gain than typically developing children. In this study, we present a comprehensive comparison of weight gain effects of five SGAs in a clinical population of youth with ASD. METHODS: We completed a subanalysis of demographic and treatment data describing 202 youth with ASD treated at two large, subspecialty psychiatry clinics. Included subjects were between 2 and 20 years of age and were treated with one of five SGAs (risperidone, aripiprazole, olanzapine, quetiapine, or ziprasidone) for up to 4 years. We calculated change in each participant's body-mass index (BMI) z-score during the treatment period using a linear model where the dependent variable was change in BMI z-score and the independent variables were SGA used and duration of treatment. First, these models were run for each drug separately, then the SGA groups were run together to estimate differences between groups. We also adjusted these models for weight gain-attenuating concomitant medications. RESULTS: Treatment with risperidone, aripiprazole, and olanzapine resulted in statistically significant increase in BMI z-score (p = 0.03, 0.05, and <0.01 respectively). Ziprasidone and quetiapine were not associated with an increase in BMI z-score in this analysis (p = 0.47 and p = 0.11). Subjects treated with olanzapine showed a statistically significant greater increase in BMI z-score when compared with the other SGAs (all p-values <0.05). These results did not change when adjusted for multiple testing or weight gain-attenuating medication as covariate. CONCLUSION: Clinicians treating youth with ASD may be able to use this information to balance the risks and benefits of SGA treatment when managing ASD-associated irritability. PMID- 27389349 TI - Fetal Growth Restriction Is Associated With Malaria in Pregnancy: A Prospective Longitudinal Study in Benin. AB - BACKGROUND: Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based follow-up study of Beninese women. METHODS: A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. RESULTS: Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with >=2 malarial parasite infections tended to have lower z scores than uninfected women. Malaria both in early and late pregnancy was associated with a reduction in fetal growth velocity, which occurred either immediately or with a delay after infection. DISCUSSIONS: We confirmed the deleterious effect of malaria during both early and late pregnancy on fetal growth. This stresses the importance of starting preventive measures against malaria as early as possible during pregnancy. PMID- 27389350 TI - Role of Interleukin 36gamma in Host Defense Against Tuberculosis. AB - Tuberculosis remains a major killer worldwide, not the least because of our incomplete knowledge of protective and pathogenic immune mechanism. The roles of the interleukin 1 (IL-1) and interleukin 18 pathways in host defense are well established, as are their regulation through the inflammasome complex. In contrast, the regulation of interleukin 36gamma (IL-36gamma), a recently described member of the IL-1 family, and its immunological relevance in host defense remain largely unknown. Here we show that Mycobacterium tuberculosis infection of macrophages induces IL-36gamma production in a 2-stage-regulated fashion. In the first stage, microbial ligands trigger host Toll-like receptor and MyD88-dependent pathways, leading to IL-36gamma secretion. In the second stage, endogenous IL-1beta and interleukin 18 further amplify IL-36gamma synthesis. The relevance of this cytokine in the control of M. tuberculosis is demonstrated by IL-36gamma-induced antimicrobial peptides and IL-36 receptor dependent restriction of M. tuberculosis growth. Thus, we provide first insight into the induction and regulation of the proinflammatory cytokine IL-36gamma during tuberculosis. PMID- 27389357 TI - Presidential Address. PMID- 27389351 TI - Schistosome Soluble Egg Antigen Decreases Mycobacterium tuberculosis-Specific CD4+ T-Cell Effector Function With Concomitant Arrest of Macrophage Phago Lysosome Maturation. AB - Helminth-infected individuals possess a higher risk of developing tuberculosis, but the precise immunologic mechanism of Mycobacterium tuberculosis control remains unclear. We hypothesized that a perturbation of the M. tuberculosis specific CD4(+) T-cell response weakens the ability of macrophages to contain M. tuberculosis We exposed peripheral blood mononuclear cells from M. tuberculosis infected humans to schistosome soluble egg antigen (SEA) and then profiled M. tuberculosis-specific CD4(+) T cells via multiparametric flow cytometry. SEA decreased the frequency of cells producing interferon gamma (6.79% vs 3.20%; P = .017) and tumor necrosis factor alpha (6.98% vs 2.96%; P = .012), with a concomitant increase in the median fluorescence intensity of interleukin 4 (IL-4; P < .05) and interleukin 10 (IL-10; 1440 vs 1273; P < .05). Macrophages polarized with SEA-exposed, autologous CD4(+) T-cell supernatant had a 2.19-fold decreased colocalization of lysosomes and M. tuberculosis (P < .05). When polarized with IL 4 or IL-10, macrophages had increased expression of CD206 (P < .0001), 1.5-fold and 1.9 fold increased intracellular numbers of M. tuberculosis per macrophage (P < .0005), and 1.4-fold and 1.7-fold decreased colocalization between M. tuberculosis and lysosomes (P < .001). This clarifies a relationship in which helminth-induced CD4(+) T cells disrupt M. tuberculosis control by macrophages, thereby providing a mechanism for the observation that helminth infection advances the progression of tuberculosis among patients with M. tuberculosis infection. PMID- 27389358 TI - A Practical Guide for Improving Transparency and Reproducibility in Neuroimaging Research. AB - Recent years have seen an increase in alarming signals regarding the lack of replicability in neuroscience, psychology, and other related fields. To avoid a widespread crisis in neuroimaging research and consequent loss of credibility in the public eye, we need to improve how we do science. This article aims to be a practical guide for researchers at any stage of their careers that will help them make their research more reproducible and transparent while minimizing the additional effort that this might require. The guide covers three major topics in open science (data, code, and publications) and offers practical advice as well as highlighting advantages of adopting more open research practices that go beyond improved transparency and reproducibility. PMID- 27389359 TI - Detection of Cryptosporidium hominis and novel Cryptosporidium bat genotypes in wild and captive Pteropus hosts in Australia. AB - Spillover of zoonotic pathogens from wildlife to humans has been identified as a primary threat to global health. In contrast, the process of reverse pathogen transmission (zooanthroponosis), whereby pathogens move from humans into wildlife species is still largely unexplored. Globally, increasing urbanisation and habitat loss are driving many wildlife species into urban and regional centres. In Australia, large numbers of flying foxes now live in close proximity to humans, increasing the risk of zooanthroponosis. The protozoan parasite Cryptosporidium is an emerging zoonotic parasite that infects a wide range of vertebrates yet there are limited studies on transmission potential of Cryptosporidium between humans and urban wildlife. To explore the presence of zooanthroponosis in flying foxes in Australia the occurrence and diversity of Cryptosporidium was investigated in urbanised wild and captive flying foxes. PCR screening of faecal samples (n=281) from seven wild sites and two captive facilities identified the presence of Cryptosporidium in 3.2% (95% CI 1.5% to 6.0%) of faecal samples. In faecal samples from wild sites Cryptosporidium occurrence was 1.7% (95% CI 0.3% to 4.8%) versus 5.9% (95% CI 2.2% to 12.4%) in samples from captive individuals, with no significant difference between captive and wild sites (p=0.077). Multilocus sequencing using three loci, 18s rDNA, actin and gp60 was used to identify Cryptosporidium in flying fox species. The host specific Cryptosporidium hominis was identified in faecal samples from two captive flying foxes, and one of these samples was confirmed as C. hominis at both actin and gp60. Sequencing of the 18s rDNA also revealed four novel Cryptosporidium genotypes in wild and captive individuals, actin and gp60 amplification and sequencing were unreliable for all four novel genotypes. These novel genotypes have been designated Cryptosporidium bat genotypes VIII-XI. This first report of Cryptosporidium spp. in Australian flying foxes indicates zooanthroponotic transmission of Cryptosporidium from humans to flying foxes within a captive environment and extends the diversity of this globally important parasite. PMID- 27389360 TI - Host and Toxoplasma gondii genetic and non-genetic factors influencing the development of ocular toxoplasmosis: A systematic review. AB - Toxoplasmosis is a cosmopolitan infection caused by the apicomplexan parasite Toxoplasma gondii. This infectious disease is widely distributed across the world where cats play an important role in its spread. The symptomatology caused by this parasite is diverse but the ocular affectation emerges as the most important clinical phenotype. Therefore, we conducted a systematic review of the current knowledge of ocular toxoplasmosis from the genetic diversity of the pathogen towards the treatment available for this infection. This review represents an update to the scientific community regarding the genetic diversity of the parasite, the genetic factors of the host, the molecular pathogenesis and its association with disease, the available diagnostic tools and the available treatment of patients undergoing ocular toxoplamosis. This review will be an update for the scientific community in order to encourage researchers to deploy cutting-edge investigation across this field. PMID- 27389361 TI - Analysis of genetic diversity in the chloroquine-resistant gene Pfcrt in field Plasmodium falciparum isolates from five regions of the southern Cameroon. AB - Understanding the population genetics of genes which shape resistance to antimalarial drugs can help in devising novel control strategies. The high spread of the resistant strains of the malaria parasite Plasmodium falciparum pose a greater challenge than before to the control programs across the world. Specific mutations in the P. falciparum chloroquine resistant transporter gene "Pfcrt" have been associated with resistance to not only chloroquine, but also to amodiaquine, one of the artemisinin partners used in Cameroon for the treatment of uncomplicated malaria. We here present data on genetic variation at the Single Nucleotide Polymorphisms (SNPs) level in the Pfcrt gene in five distinct geographical settings of the Southern-Cameroon (the most malaria endemic part), i.e. Ebolowa, Yaounde, Bertoua, Douala and Kye-ossi (a city bordering Cameroon and two others African countries). Two novel mutations, hitherto unreported (in Cameroon) were found in the Pfcrt gene and variable genetic diversity was observed across the populations. High linkage disequilibrium was found between few SNPs including one of the novel mutations suggesting a synergistic work for conferring/maintaining a higher level of resistance. The inference of evolutionary pattern of this gene in Cameroon based on the genetic diversity data depicts a signature of Darwinian positive natural selection on these loci. Observation of novel mutations might traduce new variants in chloroquine/or amodiaquine resistance (proposal awaiting an experimental verification) and signal of positive selection can be the result of drug pressure exerted by misuse of chloroquine (though officially banned from the country) and/or amodiaquine. Our findings thus, provide a baseline understanding of the evolution of a malaria drug resistant gene in Cameroon and suggest a successful establishment of chloroquine-resistant strains which requires urgent attention of the malaria control program in Cameroon. PMID- 27389362 TI - Predicting promiscuous antigenic T cell epitopes of Mycobacterium tuberculosis mymA operon proteins binding to MHC Class I and Class II molecules. AB - Limited efficacy of Bacillus Calmette-Guerin vaccine has raised the need to explore other immunogenic candidates to develop an effective vaccine against Mycobacterium tuberculosis (Mtb). Both CD4+ and CD8+ T cells play a critical role in host immunity to Mtb. Infection of macrophages with Mtb results in upregulation of mymA operon genes thereby suggesting their importance as immune targets. In the present study, after exclusion of self-peptides mymA operon proteins of Mtb were analyzed in silico for the presence of Human Leukocyte Antigen (HLA) Class I and Class II binding peptides using Bioinformatics and molecular analysis section, NetMHC 3.4, ProPred and Immune epitope database software. Out of 56 promiscuous epitopes obtained, 41 epitopes were predicted to be antigenic for MHC Class I. In MHC Class II, out of 336 promiscuous epitopes obtained, 142 epitopes were predicted to be antigenic. The comparative bioinformatics analysis of mymA operon proteins found Rv3083 to be the best vaccine candidate. Molecular docking was performed with the most antigenic peptides of Rv3083 (LASGAASVV with alleles HLA-B51:01, HAATSGTLI with HLA-A02, IVTATGLNI and EKIHYGLKVNTA with HLA-DRB1_01:01) to study the structural basis for recognition of peptides by various HLA molecules. The software binding prediction was validated by the obtained molecular docking score of peptide-HLA complex. These peptides can be further investigated for their immunological relevance in patients of tuberculosis using major histocompatibility complex tetramer approach. PMID- 27389363 TI - Reply to "Laterality of motor control as revealed in biceps electromyography: Why seizures always start in the major hemisphere". PMID- 27389364 TI - Lower face lifting and contouring with a novel internal real-time thermosensing monopolar radiofrequency. AB - As demand for a youthful appearance has increased, various techniques for face lifting and contouring have been used to reduce excess fat deposition and improve skin laxity. Recently, radiofrequency (RF)-assisted lipolysis and liposuction (RFAL) has been introduced for body and face contouring. This study aimed to evaluate the clinical improvement and safety of a new RFAL device for face lifting and contouring. A prospective study was conducted in 20 Korean patients who underwent an internal real-time thermosensing monopolar RFAL procedure. Prior to treatment and 12 and 24 weeks after treatment, digital photographs were taken, and the degree of improvement as measured by investigators and patients was recorded. Skin elasticity was measured using a Cutometer (CT575, Courage and Khazaka(r), Cologne, Germany). Safety profiles were also evaluated at each visit. Results showed favorable improvement in skin laxity and fat deposition. Both investigators' evaluations and patients' evaluation showed significant improvement between 12 and 24 weeks. Although the changes in skin elasticity measured by the Cutometer were not statistically significant, all three treated regions showed a trend toward improvement. No major side effects such as infection or burn were observed. The internal, real-time thermosensing monopolar RFAL device showed clinical efficacy and safety. After further studies with more patients and longer follow-up periods, internal real-time thermosensing monopolar RF devices might become one of the popular treatment options for face lifting and contouring. PMID- 27389365 TI - Comparison between one-session root canal treatment with aPDT and two-session treatment with calcium hydroxide-based antibacterial dressing, in dog's teeth with apical periodontitis. AB - To evaluate one-session endodontic treatment with aPDT and two-session treatment with calcium hydroxide (CH)-based dressing in dog's teeth with apical periodontitis. After experimental induction of apical periodontitis, 48 teeth were randomly assigned to the following groups: groups OS/aPDT120d and OS/aPDT180d (one-session treatment with aPDT) and groups TS/CH120d and TS/CH180d (two-session treatment with CH-based dressing-control groups). The animals were euthanized after 120 and 180 days. After histotechnical processing, microscopic and radiographic analyses were performed. Data were analyzed by Kruskal-Wallis and Fisher's exact tests (alpha = 0.05). Groups TS/CHs presented repaired resorbed cemental areas, with collagen bundles and few inflammatory cells. In groups OS/aPDTs, the areas of cemental resorption were not repaired with reduced presence of cells and fibers. In the analysis of the apical closure, fluorescence microscopy and percentage of radiographic reduction of lesions, there was significant difference between groups TS/CH120d and OS/aPDT120d and between TS/CH180d and OS/aPDT180d (p < 0.05). Groups TS/CHs had weak RANKL expression and positive immunostaining for RANK and OPG. In OS/aPDT120d, there was positive immunostaining for RANKL. In OS/aPDT180d, the three osteoclastogenesis markers were expressed. The results using aPDT were worse than those obtained with two session endodontic treatment using a CH-based dressing in teeth with apical periodontitis. PMID- 27389366 TI - Impact of calcium ion on cytotoxic effect of the boroxine derivative, K2[B3O3F4OH]. AB - The effect of Ca2+ ions on the cytotoxic ability of boron heterocyclic compound dipotassium-trioxohydroxytetrafluorotriborate (K2[B3O3F4OH]), on in vitro tumor cells (mammary adenocarcinoma 4T1, melanoma B16F10 and squamous cell carcinoma SCCVII) and non-tumoral fibroblast cells (mouse dermal L929 and hamster lung V79) was examined. At small concentrations of Ca2+ ions (0.42 mM), K2[B3O3F4OH] (3.85 mM) has a very strong cytotoxic effect on all cancer cells tested (89.1, 85.6 and 84.6%) and significantly less effect on normal cells (19.5 and 24.2%), respectively. Applying larger concentrations of Ca2+ ions (9.42-72.42 mM), at the same concentration of K2[B3O3F4OH], no significant cytotoxic effect was detected on cancer cells and normal cells investigated. The selective ability of K2[B3O3F4OH], in the medium with a low concentration of Ca2+ ions has a strong cytotoxic effect on cancer cells and very weak effect in normal cells, opens up the possibility of its application in antitumor therapy. PMID- 27389367 TI - Probing Lipophilic Adamantyl Group as the P1-Ligand for HIV-1 Protease Inhibitors: Design, Synthesis, Protein X-ray Structural Studies, and Biological Evaluation. AB - A series of potent HIV-1 protease inhibitors with a lipophilic adamantyl P1 ligand have been designed, synthesized, and evaluated. We have developed an enantioselective synthesis of adamantane-derived hydroxyethylamine isosteres utilizing Sharpless asymmetric epoxidation as the key step. Various inhibitors incorporating P1-adamantylmethyl in combination with P2 ligands such as 3-(R) THF, 3-(S)-THF, bis-THF, and THF-THP were examined. The S1' pocket was also probed with phenyl and phenylmethyl ligands. Inhibitor 15d, with an isobutyl P1' ligand and a bis-THF P2 ligand, proved to be the most potent of the series. The cLogP value of inhibitor 15d is improved compared to inhibitor 2 with a phenylmethyl P1-ligand. X-ray structural studies of 15d, 15h, and 15i with HIV-1 protease complexes revealed molecular insight into the inhibitor-protein interaction. PMID- 27389369 TI - Intraoperative electrophysiologic monitoring of the recurrent laryngeal nerve during thyroid and parathyroid surgery: Experience with 1,381 nerves at risk. AB - OBJECTIVES: The electrophysiologic responses of 1,381 recurrent laryngeal nerves (RLN) during monitored neck surgery were recorded and reviewed. STUDY DESIGN: Retrospective case series. METHODS: With institutional review board approval, we reviewed thyroid and other neck surgeries performed with intraoperative nerve monitoring (IONM) between the years 1995 and 2006. This list yielded consecutively monitored 1,381 RLNs, with over 3,000 hours of monitoring experience. All patients underwent preoperative and postoperative laryngoscopy. In an initial subset of patients, both hook-wire and endotracheal tube (ETT) surface electrodes were utilized. Normative stimulation parameters; postoperative vocal cord function prognostication using monitoring data; and false-positive, false-negative, and passive electrophysiologic responses were evaluated RESULTS: Hook-wire electrodes and ETT surface electrodes were found to have good correlation in terms of amplitude (correlation coefficient, R = 0.89). Nerve stimulation of 1 to 2 mA resulted in an ipsilateral biphasic response, with 3.3 ms mean latency and 900 MUV mean amplitude. Permanent and temporary RLN paralysis rates were 0% and 0.7%, respectively. Specificity of electromyography (EMG) loss of signal (LOS) postoperative vocal cord paralysis (VCP) detection was 99.9%, and sensitivity was 33%. Negative predictive value of EMG LOS at the end of surgery in the prediction of postoperative VCP was 99.6%, whereas its positive predictive value for VCP was 75%. CONCLUSION: Intraoperative nerve monitoring of the RLN during thyroid and other neck surgeries can aid in the nerve mapping, nerve identification, and prognostication of postoperative vocal cord function, which in turn can influence the surgeon's decision to proceed to bilateral surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:280-286, 2017. PMID- 27389368 TI - Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation. AB - Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-kappaB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-alpha and IL 6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKalpha and IKKbeta) expression and inhibit NF-kappaB signaling pathway activity; moreover, the increased miRNA-199a suppresses cholinesterases to increase cholinergic signaling, resulting in decreased expression of proinflammatory cytokines. ARC treatment confers protection for SH-SY5Y cells through positive regulation of miRNA expression, thereby reducing the inflammatory response. In turn, these effects accelerate injury repair in the scratch-induced injury model. These results might provide insights into the pharmacological role of ARC in anti-inflammation and neuroprotection in neural cells. PMID- 27389370 TI - Modified double-layered flap technique for closure of an oroantral fistula: Surgical procedure and case report. AB - Several techniques have been used to close oroantral communications, and they vary in their difficulty of execution and success. We present the "modified double-layered flap technique", which is similar to the treatment of labiopalatoschisis, has a high rate of success that is dependent on the skill of the surgeon, and will involve a steep learning curve. PMID- 27389371 TI - Sublingual gland excision: a dissection carried out following adjacent anatomical structures. AB - We describe an anatomical and simple technique for the removal of the submandibular gland that has good outcomes and minimal complications. PMID- 27389372 TI - Campaign for awareness of cancer of the head and neck in Ireland. PMID- 27389373 TI - Leading article: how can I optimise my role as a leader within the surgical team? AB - Leadership is uncommonly taught formally at any level in surgical training, and is not often evaluated formally either within assessment programmes or during appraisal. Good leadership skills in oral and maxillofacial surgery (OMFS) include professionalism, technical competence, motivation, innovation, ability to communicate, resilience, and effective teaching. They also include the recognition of when and how to "follow" when appropriate. Such skills can be developed through experience, observation, and education using a framework that can include mentoring, coaching, and feedback. This review provides some guidance in how to improve leadership skills in OMFS, which we hope will to improve the quality of training and care of patients. PMID- 27389374 TI - What is the Future of Healthcare in the United States? AB - Reports of rising costs, aging populations, budget cuts, and physician burnout can be distressing for medical professionals. Politicians tout polarizing viewpoints about how to address healthcare inequalities and improve outcomes. Litigation and insurance companies seem to have an increasing-and for some unwelcome presence in patient care. However, it is also exciting that our society today so highly values healthcare that it is a topic of heated debate. When many news outlets focus on trivial pop culture news, it is refreshing that our peers and politicians spend their time seeking to improve a system that so deeply affects our lives. It is comforting to know that issues of life and death-as well as quality of life-are not lost. There is passion in the discussion of the future of healthcare and for that, we can be grateful. PMID- 27389375 TI - Abstracts from the 2016 Annual Louisiana American College of Physicians Associates Meeting. AB - Each year medical students in Louisiana and residents from the eight Internal Medicine training programs in Louisiana are invited to submit abstracts for the Annual Louisiana American College of Physicians (ACP) Associates Meeting. The content of these abstracts includes clinical case vignettes or research activities. The abstracts have all identifying features removed (i.e., names, institutional affiliations, etc.) before being sent to physician judges. Each judge scores each abstract independently and then the scores from all judges are averaged and ranked. This year we are excited to be able to publish most highly ranked abstracts presented at this year's competition. These abstracts (17 oral; 14 poster) were presented at the Associates Meeting held at LSU Health Sciences Center in Baton Rouge on January 19, 2016. We would like to thank the Journal of the Louisiana State Medical Society and appreciate its efforts to publicize the hard work of these trainees. PMID- 27389376 TI - Integrative Family Medicine - Are Louisiana Patients Ready? AB - PURPOSE: The purpose of this preliminary study was to assess patient readiness to use a family medicine clinic that integrates complementary and alternative medicine (CAM) with conventional medicine. METHODS: A survey using the theory of planned behavior as a framework addressed patient attitudes and use of CAM. Descriptive statistics provided demographic characteristics. Additional analyses assessed differences among CAM users and responses to survey items. RESULTS: Patients who self-reported as using CAM in the past 12 months were 39.8%. The majority of patients had favorable attitudes toward CAM use and integrative medicine; 62.7% reported they are likely to use CAM if offered at the clinic. Most patients want their physician to inquire about their use of CAM (61.5%) and to be trained to treat with CAM (64%). CONCLUSIONS: Preliminary data from this study highlights patients' interest in a family medicine integrative center and may be used by providers to develop tailored messages for patients. PMID- 27389377 TI - Accidental Transorbital Penetrating Brainstem and Carotid Injury with CB Antenna: A Case Report. AB - The authors present an unusual case of a transorbital penetrating injury of the internal carotid artery and brainstem. A young man accidentally ran into a 10 foot long citizens band (CB) antenna, and presented to the emergency department with nausea, dizziness and right periorbital ecchymosis. The nature and full extent of the injury were not appreciated at the time of initial examination and computed tomography scan. Magnetic resonance imaging subsequently demonstrated an unusual brainstem lesion. Neurology consultation was obtained. The neurologist and neuroradiologists reviewed the neurological and imaging findings together. This collaboration proved critical to understanding the true nature and extent of the injury and planning evaluation and treatment. Cerebral angiography revealed a traumatic internal carotid artery dissection and pseudoaneurysm, which was treated by placement of a covered stent. The clinical symptoms remained mild and 7-year follow up shows clinical and angiographic stability. PMID- 27389378 TI - B-Cell Depletion Salvage Therapy in Rapidly Progressive Dermatomyositis Related Interstitial Lung Disease. AB - Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). Glucocorticoids are the initial standard treatment. However, many patients fail to respond and continue to progress despite treatment with high dose glucocorticoids. The efficacy of rituximab has been suggested in case reports and case series of refractory antisynthetase (AS) syndrome, but data on patients without auto-antibodies or with rapidly progressive ILD are scarce. We report a case of rapidly progressive dermatomyositis (DM) associated ILD treated successfully with B-cell depletion therapy. PMID- 27389379 TI - Intralipid Emulsion Rescue Therapy: Emerging Therapeutic Indications in Medical Practice. AB - Intralipid emulsion therapy is well-established for the treatment of local anesthetic systemic toxicities. In recent years, its role has expanded as an important therapeutic agent in the reversal of other types of drug overdoses, including certain types of antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. A literature review identified thirty-one case reports including forty-nine separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The present clinical case study describes an elderly unresponsive woman refractory to conventional treatments after ingesting a potentially lethal amount of 5.6 grams of diltiazem in a suicide attempt. After treatment with Intralipid over a twenty-four hour period, the patient's hemodynamic and metabolic derangements were corrected and stabilized completely. Intralipid emulsion rescue therapy provides another potential strategy for the reversal of many drug toxicities, most likely by providing a lipid layer safety net for drug overdose by passive diffusion. Clinicians are urged to embrace an expanded role of Intralipid emulsion rescue therapy, not only for local anesthetic drug toxicities, but also for other lipophilic drug overdoses. PMID- 27389380 TI - Management of Complications of Acute Otomastoiditis in Solid Organ Transplant Patients. AB - BACKGROUND: There are over 183,000 patients living with a functioning solid organ transplant in the United States, and almost no data exist discussing complications of acute otomastoiditis in this vulnerable population. Early recognition and treatment of acute otomastoiditis is essential in patients whose immune system is not normal, as progression can lead to sepsis, meningitis, brain abscess, Bezold's abscess, sigmoid sinus thrombosis, or other potentially fatal sequelae. METHODS: Case report with extensive literature review. RESULTS: A 63 year-old man presented 3 years after cadaveric renal transplant with otorrhea and altered mental status. His acute otitis media progressed to meningitis with sigmoid sinus thrombosis and sepsis, and management included IV and otic antibiotics, tympanostomy tube placement, and cortical mastoidectomy. The patient made a full recovery without residual neurologic deficit. CONCLUSION: Extrapolating data from patients immunosuppressed for other reasons, patients immunosuppressed after solid organ transplant should receive prompt recognition and aggressive treatment of acute otomastoiditis to prevent or address potentially devastating intracranial or systemic complications. PMID- 27389381 TI - Obstructive Jaundice from Metastatic Squamous Cell Carcinoma of the Lung. AB - Obstructive jaundice from metastatic lung cancer is extremely rare. Most reported cases have had small cell cancer of lung or adenocarcinoma of lung as primary malignancy metastasizing to the biliary system. We report the case of a patient presenting with symptoms of obstructive jaundice found to have metastatic involvement of hepatobiliary system from squamous cell cancer (SCC) of lung. ERCP (endoscopic retrograde cholangiopancreatography) with biliary stenting is the procedure of choice in such patients. Our case is made unique by the fact that technical difficulties made it difficult for the anesthesiologists to intubate the patient for an ERCP. As a result percutaneous transhepatic cholangiogram (PTC) with internal-external biliary drainage was performed. PMID- 27389382 TI - Pathology Image Of the Month: Rapidly Progressive Hemorrhagic Cellulitis of Bilateral Lower Extremities with Subsequent Septic Shock and Death. AB - A 51-year-old man presented to a community based emergency department with bilateral lower extremity swelling that began four days prior and that had evolved into recent blister formation on the left lower extremity. Medical history was significant only for hypertension and a recent self-described episode of "food poisoning" five days earlier characterized by diarrhea, nausea, and vomiting that quickly resolved. Physical exam revealed marked bilateral lower extremity edema and an ecchymotic rash below the knee. In addition to the rash, there were large flaccid bullae on the left leg, mostly intact but some notable for draining of scanty serosanguinous fluid. The patient was tachycardic with a rate of 114 bpm and initial labs showed thrombocytopenia (platelets 56 x 103/uL [140-440 x 103/uL]), hypoglycemia (15mg/dl [70-105mg/dl]), an elevated creatinine (2.7mg/dL [0.7- 1.25mg/dL]), and aspartate aminotransferase (AST 156U/L [5- 34U/L]). Two sets of blood cultures were drawn, broad spectrum antibiotics including doxycycline were empirically initiated and then he was subsequently transported to a tertiary care hospital for escalation of care. Within hours of presentation to the tertiary care facility, the rash appeared progressively hemorrhagic and bullous, lactic acidosis and coagulopathy developed and hemodynamic instability and septic shock necessitated endotracheal intubation and vasopressors. He was taken to the operating room for skin debridement but was emergently converted to bilateral above the knee lower extremity amputations due to the extent of the soft tissue necrosis. The patient remained intubated and in critical condition following surgery and the ecchymotic rash reappeared at the amputation sites. A newly developed ecchymotic rash with bullae formation was noted on the right upper extremity forearm. At that time, the clinicians were notified that four out of four blood culture bottles from admission were rapidly growing a microorganism. The family elected for withdrawal of care, and the patient died approximately 72 hours following presentation. A full and unrestricted autopsy was authorized by the Coroner's Office. PMID- 27389383 TI - ECG Of The Month: Sepsis, ARDS, and Tracheal Intubation. AB - A furuncle on the leg of a 23-year-old woman led to methicillin-resistant staphylococcus aureus sepsis and adult respiratory distress syndrome (ARDS) requiring tracheal intubation in the intensive care unit (ICU). Initially her electrocardiograms (ECGs) showed sinus tachycardia, but otherwise were unchanged from prior ECGs. A week into her ICU stay a different rhythm occurred. PMID- 27389384 TI - Clinical Case Of the Month: A 35 Year Old Woman with Abdominal Pain. AB - A 35 year old woman with past medical history of hypertension presented to the emergency department with chief complaint of severe abdominal pain for one week. The abdominal pain was located in the epigastrium and described as "cramping" and "intermittent". The pain intensity was quantified initially as 6 out of 10 on the pain scale. As the week progressed the pain became constant and radiated to the back. The intensity of the abdominal pain increased to 10 out of 10. The patient reported some relief from her pain while lying in the prone position. Initially the pain was associated with loose stools for several days. The loose stools resolved spontaneously and then the patient began to experience nausea and vomiting. Her medications included lisinopril-hydrochlorothiazide which she had been taking for the past five months. She had no history of alcohol, tobacco or illicit drug use. PMID- 27389385 TI - Radiology Of The Month: Spontaneous Bilateral Pneumothoraces in an HIV-Infected Patient. AB - A 36-year-old woman with past medical history of HIV/AIDS not on HAART therapy (CD4 count of 34) and recurrent Pneumocystis jiroveci pneumonia presented to the emergency room for cough, chest pain, and worsening shortness of breath over the past 72 hours. PMID- 27389386 TI - Recipient and donor JAK2 46/1 haplotypes are associated with acute graft-versus host disease following allogeneic hematopoietic stem cell transplantation. AB - Several genetic polymorphisms have been implicated to affect the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of cytokines in acute graft-versus-host disease (aGvHD) is well established and many of the involved cytokines signal through the Janus kinase (JAK) pathways. In this study, we assessed the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 acute myeloid leukemia patients. Both, recipient and donor 46/1 haplotypes significantly affected aGvHD grades II-IV development (p = 0.006 and p = 0.031, respectively), furthermore the influence of the haplotypes seemed to be additive. In multivariate analyses the recipient haplotype remained independently related (p = 0.012) to aGvHD, while the donor not (p = 0.08). We observed significantly less relapses among haplotype carriers (p = 0.004), but overall survival did not differ (p = 0.732). Our findings suggest that recipient and donor JAK2 46/1 haplotypes might be involved in the regulation of aGvHD. PMID- 27389387 TI - [Clinical Trial to Test the iFuse Implant System(r) in Patients with Sacroiliac Joint Syndrome: One Year Results]. AB - Background: This study reports one year post-operative monitoring of the efficacy and safety of iFuse Implant System(r) in patients with sacroiliac joint syndrome. Material and Methods: After 6 months of inadequate conservative treatment, patients with properly proven ISG syndrome were selected for surgery. The iFuse implants had a triangular profile and coating of porous titanium plasma spray and were used in the minimally invasive procedures. The procedure was performed under general anaesthesia and fluoroscopic control. In each case, three implants were placed. Results: 24 patients (22 f; 92 %; 54.9 +/- 14 years) participated in the study. The operations were performed in 11 patients (46 %) on the left and in 13 patients (54 %) on the right. The mean operative time was 42.4 minutes (95 % CI: 35.6-49.3). The reduction in pain intensity on the VAS scale was 58 +/- 11 mm (68 +/- 7 %). The Oswestry score showed a median decrease of 44 percentage points (57 %). After 12 months, 15 patients (63 %) reported that they were taking no more painkillers. Conclusion: The minimally invasive treatment of patients with sacroiliac joint syndrome using the iFuse Implant System leads to significant analgesic effects over the period of one year; it also contributes significantly to improving the functioning of the patient. PMID- 27389388 TI - [The Significance of Early Reposition in Patients with Visible Malposition of the Upper Ankle Joint]. AB - Background: Protracted dislocation of the upper ankle joint can lead to substantial damage to the surrounding soft tissue, possibly followed by local complications and longer hospitalisation. Although reposition is usually easy to conduct, it is commonly recommended that this should only be performed by an experienced specialist, as long as there is no neurovascular restriction. There are however no exact data or studies on this problem. The aim of the present study is to examine whether early reposition is of benefit for subsequent treatment. Methods: Retrospective study of all patients in a supra-regional trauma centre during the period from January 2009 to July 2015, with either prehospital reposition of the ankle joint because of visible malposition or documented visible malposition on arrival at hospital. Patients with relevant concomitant injuries elsewhere were excluded. Data on the duration of dislocation were matched with diagnostic findings at the time of hospital admission, the kind of primary care, local complications and the time of hospitalisation, using linear regression analysis and ANOVA calculations. Results: Of a total of 391 patients with a dislocation or a fracture dislocation of the ankle joint within this period, 132 fulfilled the inclusion criteria. These patients were divided into 5 groups on the basis of the time of dislocation. Time to reposition was less than one hour for 39 patients, between one and two hours for 29 patients, between two and six hours for 41 patients, between six and 24 hours for 13 patients and more than 24 hours for 10 patients, all with a visible dislocation. The results on admission showed a significant increase in skin bruises and tension bullae with increasing time of dislocation. A longer time of dislocation was associated with more two stage surgical procedures with external fixators and a decreasing number of single stage procedures. While there was immediate definitive treatment of 79.5 % of the patients in the first group, this figure decreased continuously to 10.0 % in the last group. The number of local complications increased significantly in every group with the duration of dislocation. In particular, the incidence of severe swelling, wound healing disorders, skin necrosis and the need for revision surgery and plastic reconstruction exhibit a significant linear increase within the groups (p < 0.05). The incidence of severe swelling rose from 10.3 % in the first group, to 31.0 % in the second group, to 100 % in the last group. The incidence of wound healing disorders rose from 7.7 to 13.8 to 80 % and the incidence of skin necrosis from 2.6 to 3.5 to 30.0 %. The duration of hospitalisation also exhibited a significant linear increase with group affiliation (p < 0.001), from 8.3 days in the first group to 12.5 days in the second group and 30.5 days in the last group. Conclusion: This study shows the importance of conducting reposition of the ankle joint as soon as possible if there is visible malposition, in order to avoid local complications and longer hospitalisation. If there is visible malposition of the ankle joint, the best procedure is immediate - ideally prehospital - reposition and in-axis splinting, in order to preserve soft tissue. PMID- 27389390 TI - Control of drop shape transformations in cooled emulsions. AB - The general mechanisms of structure and form generation are the keys to understanding the fundamental processes of morphogenesis in living and non-living systems. In our recent study (Denkov et al., Nature 528 (2015) 392) we showed that micrometer sized n-alkane drops, dispersed in aqueous surfactant solutions, can break symmetry upon cooling and "self-shape" into a series of geometric shapes with complex internal structure. This phenomenon is important in two contexts, as it provides: (a) new, highly efficient bottom-up approach for producing particles with complex shapes, and (b) remarkably simple system, from the viewpoint of its chemical composition, which exhibits the basic processes of structure and shape transformations, reminiscent of morphogenesis events in living organisms. In the current study, we show for the first time that drops of other chemical substances, such as long-chain alcohols, triglycerides, alkyl cyclohexanes, and linear alkenes, can also evolve spontaneously into similar non spherical shapes. We demonstrate that the main factors which control the drop "self-shaping", are the surfactant type and chain length, cooling rate, and initial drop size. The studied surfactants are classified into four distinct groups, with respect to their effect on the "self-shaping" phenomenon. Coherent explanations of the main experimental trends are proposed. The obtained results open new prospects for fundamental and applied research in several fields, as they demonstrate that: (1) very simple chemical systems may show complex structure and shape shifts, similar to those observed in living organisms; (2) the molecular self-assembly in frustrated confinement may result in complex events, governed by the laws of elasto-capillarity and tensegrity; (3) the surfactant type and cooling rate could be used to obtain micro-particles with desired shapes and aspect ratios; and (4) the systems studied serve as a powerful toolbox to investigate systematically these phenomena. PMID- 27389389 TI - Evaluation of laser bacterial anti-fouling of transparent nanocrystalline yttria stabilized-zirconia cranial implant. AB - BACKGROUND AND OBJECTIVE: The development and feasibility of a novel nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant has been recently established. The purpose of what we now call "window to the brain (WttB)" implant (or platform), is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for enhancing light-based diagnosis and treatment of a wide variety of brain pathologies including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases. However, bacterial adhesion to the cranial implant is the leading factor for biofilm formation (fouling), infection, and treatment failure. Escherichia coli (E. coli), in particular, is the most common isolate in gram-negative bacillary meningitis after cranial surgery or trauma. The transparency of our WttB implant may provide a unique opportunity for non invasive treatment of bacterial infection under the implant using medical lasers. STUDY DESIGN/MATERIALS AND METHODS: A drop of a diluted overnight culture of BL21 293 E. coli expressing luciferase was seeded between the nc-YSZ implant and the agar plate. This was followed by immediate irradiation with selected laser. After each laser treatment the nc-YSZ was removed, and cultures were incubated for 24 hours at 37 degrees C. The study examined continuous wave (CW) and pulsed wave (PW) modes of near-infrared (NIR) 810 nm laser wavelength with a power output ranging from 1 to 3 W. During irradiation, the temperature distribution of nc-YSZ surface was monitored using an infrared thermal camera. Relative luminescence unit (RLU) was used to evaluate the viability of bacteria after the NIR laser treatment. RESULTS: Analysis of RLU suggests that the viability of E. coli biofilm formation was reduced with NIR laser treatment when compared to the control group (P < 0.01) and loss of viability depends on both laser fluence and operation mode (CW or PW). The results demonstrate that while CW laser reduces the biofilm formation more than PW laser with the same power, the higher surface temperature of the implant generated by CW laser limits its medical efficacy. In contrast, with the right parameters, PW laser produces a more moderate photothermal effect which can be equally effective at controlling bacterial growth. CONCLUSIONS: Our results show that E. coli biofilm formation across the thickness of the nc-YSZ implant can be disrupted using NIR laser treatment. The results of this in vitro study suggest that using nc-YSZ as a cranial implant in vivo may also allow for locally selective, non-invasive, chronic treatment of bacterial layers (fouling) that might form under cranial implants, without causing adverse thermal damage to the underlying host tissue when appropriate laser parameters are used. Lasers Surg. Med. 48:782-789, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27389391 TI - Comparing the case mix and survival of women receiving breast cancer care from one private provider with other London women with breast cancer: pilot data exchange and analyses. AB - BACKGROUND: Data from providers of private cancer care are not yet formally included in English cancer registration data. This study aimed to test the exchange of breast cancer data from one Hospital Corporation of America International (HCAI) hospital in London with the cancer registration system and assess the suitability of these data for comparative analyses of case mix and adjusted survival. METHODS: Data on 199 London women receiving 'only HCAI care', 278 women receiving 'some HCAI care' (HCAI and other services), and 31,234 other London women diagnosed between 2005 and 2011 could be identified and compared. Overall survival was estimated using the Kaplan-Meier method, and Cox regression was used to adjust for age, socioeconomic deprivation, year of diagnosis, stage of disease and recorded treatment. RESULTS: Women receiving 'only HCAI care' were younger, lived in areas of higher affluence (47.8 % vs 27.6 %) and appeared less likely to be recorded as having screen-detected (2.5 % vs 25.0 %) disease than other London women. Women receiving 'some HCAI care' were more similar to 'HCAI only' women. Although HCAI stage of disease data completeness improved during the study period, this was less complete overall than cancer registration data and limited the comparative survival analyses. An apparent survival advantage for 'HCAI only' women compared with other London women (hazard ratio 0.48, 95 % confidence interval (CI): 0.32-0.74) was attenuated and no longer statistically significant after adjustment (0.79, 95 % CI: 0.51-1.21). Women receiving 'some HCAI care' appeared to have higher survival (hazard ratio 0.24, 95 % CI 0.14 0.41) which was attenuated to 0.48 (95 % CI: 0.28-0.80) in the fully adjusted model. CONCLUSIONS: Exchange of data between the private cancer sector and the English cancer registration service can identify patients who receive all or some private care. The better survival of women receiving only or some HCAI breast cancer care appears to be at least partly explained by demographic, disease, and treatment factors. However, larger studies using similarly quality assured datasets and more complete staging data from the private sector are needed to produce definitive comparative results. PMID- 27389392 TI - Anti-atherosclerotic potential of baicalin mediated by promoting cholesterol efflux from macrophages via the PPARgamma-LXRalpha-ABCA1/ABCG1 pathway. AB - BACKGROUND: Atherosclerosis (AS) is associated with severe cardiovascular disease. The anti-inflammatory, anti-oxidation, and lipid regulating properties of baicalin suggest potential as an anti-atherosclerotic agent. We therefore investigated whether baicalin can protect against the development of atherosclerosis in an AS rabbit model and explored the underling mechanisms in THP-1 macrophages. METHODS AND RESULTS: In vivo, treatment with baicalin markedly decreased atherosclerotic lesion sizes and lipid accumulation in AS rabbit carotid arteries. Western blotting revealed that the protein expression levels of both peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) were up-regulated in the baicalin group compared with the model group. In vitro, baicalin restricted oxidized-low density lipoprotein (ox-LDL)-induced intracellular lipid accumulation and foam cell formation in THP 1 macrophages. Molecular data showed that baicalin significantly increased the expression levels of PPARgamma, LXRalpha, ATP binding cassette transporters (ABC) A1 and ABCG1. Cell transfection experiments (including PPARgamma and LXRalpha siRNAs) suggested that the effects of baicalin are mediated by the PPARgamma LXRalpha signalling pathway, which stimulates the expression of ABCA1 and ABCG1. CONCLUSION: These results suggest that baicalin potentially exerts anti atherosclerosis effects, possibly through the PPARgamma-LXRalpha-ABCA1/ABCG1 pathway, by promoting efflux of cholesterol from macrophages and delaying the formation of foam cells. PMID- 27389393 TI - Titania nanotubes for orchestrating osteogenesis at the bone-implant interface. AB - Titanium implants can fail due to inappropriate biomechanics at the bone-implant interface that leads to suboptimal osseointegration. Titania nanotubes (TNTs) fabricated on Ti implants by the electrochemical process have emerged as a promising modification strategy to facilitate osseointegration. TNTs enable augmentation of bone cell functions at the bone-implant interface and can be tailored to incorporate multiple functionalities including the loading of active biomolecules into the nanotubes to target anabolic processes in bone conditions such as osteoporotic fractures. Advanced functions can be introduced, including biopolymers, nanoparticles and electrical stimulation to release growth factors in a desired manner. This review describes the application of TNTs for enhancing osteogenesis at the bone-implant interface, as an alternative approach to systemic delivery of therapeutic agents. PMID- 27389394 TI - Metachromatic Leukodystrophy: An Assessment of Disease Burden. AB - Metachromatic leukodystrophy is accompanied by severe motor and cognitive dysfunction. This is the first survey of metachromatic leukodystrophy caregiver perspectives to identify relevant clinical/quality-of-life outcomes for patients/caregivers. Interviews and 1 focus group were conducted with 30 caregivers representing 23 patients. Caregivers were asked about their experiences, including diagnostic process, signs/symptoms, symptoms affecting caregivers' and patients' lives, and treatment priorities. Caregivers reported loss of physical autonomy, weight loss, limited social relationships, frequent crying, and challenging sibling relationships. Most troublesome symptoms were immobility (9/30) and respiratory difficulties (6/30). Health care visits were frequent: 8/22 patients had experienced >=11 hospitalizations since diagnosis, and 14/22 caregivers reported that these lasted >=4 days. Caregivers also experienced work problems, feelings of fear/sadness, and loss of social relationships. Caregivers/physicians consider a therapy that could improve decline in mobility, pain, cognitive ability, communication, or food intake as conferring the greatest benefit. In conclusion, a so-far-unreported physical/economic burden in these families is presented. PMID- 27389395 TI - Multiple-genotype infections and their complex effect on virulence. AB - Multiple infections are common. Although in recent years our understanding of multiple infections has increased significantly, it has also become clear that a diversity of aspects has to be considered to understand the interplay between co infecting parasite genotypes of the same species and its implications for virulence and epidemiology, resulting in high complexity. Here, we review different interaction mechanisms described for multiple infections ranging from competition to cooperation. We also list factors influencing the interaction between co-infecting parasite genotypes and their influence on virulence. Finally, we emphasise the importance of between-host effects and their evolution for understanding multiple infections and their implications. PMID- 27389396 TI - A High Malaria Prevalence Identified by PCR among Patients with Acute Undifferentiated Fever in India. AB - BACKGROUND: Approximately one million malaria cases were reported in India in 2015, based on microscopy. This study aims to assess the malaria prevalence among hospitalised fever patients in India identified by PCR, and to evaluate the performance of routine diagnostic methods. METHODS: During June 2011-December 2012, patients admitted with acute undifferentiated fever to seven secondary level community hospitals in Assam (Tezpur), Bihar (Raxaul), Chhattisgarh (Mungeli), Maharashtra (Ratnagiri), Andhra Pradesh (Anantapur) and Tamil Nadu (Oddanchatram and Ambur) were included. The malaria prevalence was assessed by polymerase chain reaction (PCR), routine microscopy, and a rapid diagnostic test (RDT) with PCR as a reference method. RESULTS: The malaria prevalence by PCR was 19% (268/1412) ranging from 6% (Oddanchatram, South India) to 35% (Ratnagiri, West India). Among malaria positive patients P. falciparum single infection was detected in 46%, while 38% had P. vivax, 11% mixed infections with P. falciparum and P. vivax, and 5% P. malariae. Compared to PCR, microscopy had sensitivity of 29% and specificity of 98%, while the RDT had sensitivity of 24% and specificity of 99%. CONCLUSIONS: High malaria prevalence was identified by PCR in this cohort. Routine diagnostic methods had low sensitivity compared to PCR. The results suggest that malaria is underdiagnosed in rural India. However, low parasitaemia controlled by immunity may constitute a proportion of PCR positive cases, which calls for awareness of the fact that other pathogens could be responsible for the febrile disease in submicroscopic malaria. PMID- 27389397 TI - A case report of malignant hypertension in a young woman. AB - BACKGROUND: Malignant hypertension is a condition characterized by severe hypertension and multi-organ ischemic complications. Albeit mortality and renal survival have improved with antihypertensive therapy, progression to end-stage renal disease remains a significant cause of morbidity and mortality. The underlying cause of malignant hypertension, which can be primary or secondary hypertension, is often difficult to identify and this can substantially affect the treatment outcomes, as we report here. CASE PRESENTATION: A 33-year-old woman presented with severe hypertension and acute renal failure. Initial evaluation demonstrated hyperreninemia with hyperaldosteronism and a possible renal artery stenosis at the contrast-enhanced CT scan. Although this data suggested the presence of a secondary form of hypertension, further exams excluded our first diagnosis of renal artery stenosis. Consequently, the patient did not undergo renal angiography (and the contrast media infusion associated with it), but she continued to be medically treated to achieve a tight blood pressure control. Our conservative approach was successful to induce renal function recovery over 2 years of follow-up. CONCLUSION: This case highlights the difficulty in differentiating between primary and secondary forms of malignant hypertension, particularly when the patient presents with acute renal failure. Clinicians should consider renal artery ultrasound as a first level diagnostic technique, given that the presentation of primary malignant hypertension can often mimic a renal artery stenosis. Secondly, adequate control of blood pressure is essential for kidney function recovery, although this may require a long time. PMID- 27389398 TI - Estimating Indoor PM2.5 and CO Concentrations in Households in Southern Nepal: The Nepal Cookstove Intervention Trials. AB - High concentrations of household air pollution (HAP) due to biomass fuel usage with unvented, insufficient combustion devices are thought to be an important health risk factor in South Asia population. To better characterize the indoor concentrations of particulate matter (PM2.5) and carbon monoxide (CO), and to understand their impact on health in rural southern Nepal, this study analyzed daily monitoring data collected with DataRAM pDR-1000 and LASCAR CO data logger in 2980 households using traditional biomass cookstove indoor through the Nepal Cookstove Intervention Trial-Phase I between March 2010 and October 2011. Daily average PM2.5 and CO concentrations collected in area near stove were 1,376 (95% CI, 1,331-1,423) MUg/m3 and 10.9 (10.5-11.3) parts per million (ppm) among households with traditional cookstoves. The 95th percentile, hours above 100MUg/m3 for PM2.5 or 6ppm for CO, and hours above 1000MUg/m3 for PM2.5 or 9ppm for CO were also reported. An algorithm was developed to differentiate stove influenced (SI) periods from non-stove-influenced (non-SI) periods in monitoring data. Average stove-influenced concentrations were 3,469 (3,350-3,588) MUg/m3 for PM2.5 and 21.8 (21.1-22.6) ppm for CO. Dry season significantly increased PM2.5 concentration in all metrics; wood was the cleanest fuel for PM2.5 and CO, while adding dung into the fuel increased concentrations of both pollutants. For studies in rural southern Nepal, CO concentration is not a viable surrogate for PM2.5 concentrations based on the low correlation between these measures. In sum, this study filled a gap in knowledge on HAP in rural Nepal using traditional cookstoves and revealed very high concentrations in these households. PMID- 27389399 TI - Fear Similarly Alters Perceptual Estimates of and Actions over Gaps. AB - Previous research has demonstrated an influence of one's emotional state on estimates of spatial layout. For example, estimates of heights are larger when the viewer is someone typically afraid of heights (trait fear) or someone who, in the moment, is experiencing elevated levels of fear (state fear). Embodied perception theories have suggested that such a change in perception occurs in order to alter future actions in a manner that reduces the likelihood of injury. However, other work has argued that when acting, it is important to have access to an accurate perception of space and that a change in conscious perception does not necessitate a change in action. No one has yet investigated emotional state, perceptual estimates, and action performance in a single paradigm. The goal of the current paper was to investigate whether fear influences perceptual estimates and action measures similarly or in a dissociable manner. In the current work, participants either estimated gap widths (Experiment 1) or were asked to step over gaps (Experiment 2) in a virtual environment. To induce fear, the gaps were placed at various heights up to 15 meters. Results showed an increase in gap width estimates as participants indicated experiencing more fear. The increase in gap estimates was mirrored in participants' stepping behavior in Experiment 2; participants stepped over fewer gaps when experiencing higher state and trait fear and, when participants actually stepped, they stepped farther over gap widths when experiencing more fear. The magnitude of the influence of fear on both perception and action were also remarkably similar (5.3 and 3.9 cm, respectively). These results lend support to embodied perception claims by demonstrating an influence on action of a similar magnitude as seen on estimates of gap widths. PMID- 27389400 TI - Active chemical fractions of stem bark extract of Khaya grandifoliola C.DC and Entada africana Guill. et Perr. synergistically protect primary rat hepatocytes against paracetamol-induced damage. AB - BACKGROUND: Khaya grandifoliola (Meliaceae) and Entada africana (Fabaceae) are traditionally used in Bamun (a western tribe of Cameroon) traditional medicine for the treatment of liver related diseases. In this study, the synergistic hepatoprotective effect of respective active fractions of the plants were investigated against paracetamol-induced toxicity in primary cultures of rat hepatocytes. METHODS: Paracetamol conferred hepatocyte toxicity, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) activities, malondialdehyde (MDA) and glutathione (GSH) content assays. The crude extracts were fractionated by flash chromatography and fractions were tested for hepato (protective and curative) activities. The most active fractions of both plants were tested individually, and in combination based on their respective half effective concentration (EC50). RESULTS: The methylene chloride/methanol fractions of K. grandifoliola (75:25 v/v) (KgF25) and E. africana (90:10 v/v) (EaF10) were found to be the most hepato-protective with EC50 values of 10.30 +/- 1.66 MUg/ml and 13.47 +/- 2.06 MUg/ml respectively, comparable with that of silymarin (13.71 +/- 3.87 MUg/ml). These fractions and their combination significantly (P <0.05) improved cell viability, inhibited ALT leakage and MDA formation, and restored cellular CAT, SOD activities and GSH content. The combination was more effective in restoring biochemical parameters with coefficients of drugs interaction (CDI) less than 1. CONCLUSION: These findings demonstrate that the active fractions have synergistic action in the protection of rat hepatocytes against paracetamol-induced damage and suggest that their hepatoprotective properties may be maximized by using them in combination. PMID- 27389401 TI - Commensal-Pathogen Interactions along the Human Nasal Passages. PMID- 27389402 TI - Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device. AB - BACKGROUND: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. METHODS: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. RESULTS: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. CONCLUSIONS: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01163825 . Registered on 14 Jul 2010. PMID- 27389403 TI - Pharmacokinetics and Tolerability of Anti-Hepatitis C Virus Treatment with Ombitasvir, Paritaprevir, Ritonavir, with or Without Dasabuvir, in Subjects with Renal Impairment. AB - BACKGROUND: The direct-acting antiviral agent (DAA) combination of ombitasvir and paritaprevir (administered with ritonavir) with (3D regimen) or without (2D regimen) dasabuvir has shown very high efficacy rates in the treatment of chronic hepatitis C virus (HCV) infection. Renal impairment, a common comorbidity in patients with chronic HCV infection, can influence the pharmacokinetics of antiviral agents and hence their efficacy and safety profiles. OBJECTIVE: The aim of this study was to evaluate the influence of renal impairment on the pharmacokinetics and tolerability of the 3D and 2D regimens. METHODS: Overall, 24 subjects, six in each of four renal function groups (normal, mild, moderate, and severe), received a single dose of the 3D and 2D regimens in separate dosing periods. Plasma and urine were analyzed to assess the effect of renal impairment on drug exposure. RESULTS: DAA exposures changed by up to 21, 37, and 50 % in subjects with mild, moderate, and severe renal impairment, respectively, versus subjects with normal renal function. Ritonavir exposure increased with the degree of renal impairment (maximum 114 %). The half-lives of DAAs and ritonavir in subjects with renal impairment were generally comparable with those in healthy subjects. No safety or tolerability concerns arose in this study. CONCLUSION: The 3D and 2D regimens do not require dose adjustment for patients with HCV infection and concomitant renal impairment. PMID- 27389404 TI - A Strategy for Dosing Vancomycin to Therapeutic Targets Using Only Trough Concentrations. AB - Effective treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin requires a 24-h area under the concentration time curve (AUC24) to minimum inhibitory concentration (MIC) ratio of at least 400. To ensure goal AUC24 has been reached requires either dosing to concentrations strongly associated with nephrotoxicity, measurement of patient specific pharmacokinetics, or use of Bayesian statistics. In this study, we show a method of determining patient-specific pharmacokinetics and dosing to therapeutic AUC24 while minimizing potentially toxic concentrations, guided by only trough measurements. A Monte-Carlo simulation of 10,000 patients with complicated MRSA infections was prepared from two-compartment pharmacokinetic parameters using patient data extracted from the literature. The proposed method of determining patient-specific pharmacokinetics using consecutive trough concentrations was found to be more accurate than the conventional peak-trough method for peaks measured up to 4 h after infusion. Simulated human error in trough timing was found to reduce accuracy of the consecutive trough method, but an approach to resolve timing errors during a loading sequence or at steady-state using iteration is proposed. Both the simulated minimized concentration strategy and trough-based dosing to 15-20 mg/L had a high probability of achieving AUC24 at least 400 mg.h/L, but conventional trough-based dosing was associated with higher probability of potentially toxic 24-h doses and trough concentrations. The proposed strategy must be validated in real patients, with outcomes assessed before it is used in daily practice, but the theoretical benefits found in the simulation suggest this simple strategy should be considered with other AUC24 based approaches. PMID- 27389405 TI - Diagnosis and Prevalence of Prominent Lobules in Otoplasty: Analysis of 120 Patients with Prominent Ears. AB - BACKGROUND: The prominence of the ear lobule is considered an anomaly of secondary importance and receives correspondingly less attention in literature. We reviewed a case series of otoplasty patients and analyzed the prevalence of lobule prominence. METHODS: Records of otoplasties between 2007 and 2013 were reviewed. Inclusion criteria were: (1) primary otoplasties; (2) prominence of both ears; and (3) otoplasties conducted by the main author. Patients were divided into two groups: (1) A general group (GG) containing all the patients, and (2) a lobule correction group (LG)-a subgroup of GG containing only the patients who needed lobule correction. RESULTS: From a total of 291 patients, 120 patients were included in GG and 27 patients in LG. There was no statistical difference between groups GG and LG in terms of age and gender. Preoperative diagnosis of lobule prominence was correctly established in 14 patients; 13 patients were diagnosed during surgery. CONCLUSIONS: Lobule prominence should not be underestimated since its diagnosis may be missed in the preoperative period nearly 50 % in our case. Also its prevalence (22.5 %) is not as infrequent as some may think. Knowledge of lobule correction techniques before surgery is important to avoid less than optimal results in otoplasty. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 27389406 TI - Erratum to: Current Trends in the Oncologic and Surgical Managements of Breast Cancer in Women with Implants: Incidence, Diagnosis, and Treatment. PMID- 27389407 TI - Application of Nipple Retractor for Correction of Nipple Inversion: A 10-Year Experience. AB - BACKGROUND: Nipple inversion is a relatively common problem in adolescent and adult women; however, most present surgical treatments are prone to injure the lactiferous ducts and impair the breast feeding function. A nipple retractor was developed by us in 2003 to correct nipple inversion to avoid lactiferous duct injury. The details and a 10-year evaluation of this technique were introduced in this paper. METHODS: The nipple retractor was made from the hollow end of single use syringe, then eight holes were punctured for sutures crossing the base, and the height of retractor depended on the sizes of nipple-areola complex and breast volume. Two sutures were made to cross beneath the base of the nipple to elevate the nipple, and the hollow retractor was placed on the areola with the nipple and four ends of the sutures in the center, sutures then passed the prefabricated holes on the retractor base and were fixed with knots and suitable tension. The retractor was worn for 3-6 months and then could be removed. RESULTS: A total of 257 nipples in 136 patients with nipple inversion (unilateral: 15 patients; bilateral: 121 patients) received this operation from Jan 2003 to Dec 2012, among which 233 nipples were successfully corrected (90.7 %), and 24 nipples reoccurred in 2 years. The effective rates of grade I and grade II inversions were significantly higher than that of grade III (P < 0.01). Thirty-two patients with 56 treated nipples underwent labor and breastfeeding, and all the nipples were functional. The complications included fistula after suture removal (19 nipples, 7.4 %), breaking of suture (8 nipples, 3.1 %), erosion of nipple (28 nipples, 10.9 %), and chronic pain (10 nipples, 3.4 %), and all these complications were properly managed. CONCLUSION: The nipple retractor technique is a feasible, effective, and safe method for correction of grade I and grade II nipple inversions, and could also be indicated for primary correction of grade III inversion. Its most significant advantage is that lactiferous duct injury can be avoided and the breast feeding function preserved. LEVEL OF EVIDENCE V: Nipple inversion is a common malformation in adolescent and adult women, which can be present unilaterally or bilaterally. It was generally initiated from the adolescent period and could be caused by primary hypogenesis of smooth muscle and supporting tissue of the nipple-areola complex or hypoplasia of lactiferous ducts [1] . Some other secondary factors such as chronic infection, tumor, and previous surgery could contribute to the fibrosis, and some of them were believed to be congenital and hereditary [2, 3]. Since the openings of lactiferous ducts are immersed, inversion might cause reoccurring infection and breast feeding difficulty, and the appearance of the breast would be affected as well, which would impact patients' psychological health. Nipple inversion can be clinically divided into three categories according to Han et al.'s grading rules. In grade I, the nipple is easily pulled out manually and maintains its projection quite well. In grade II, the nipples can be pulled out but cannot maintain projection and tend to go back again. In grade III, the nipple can hardly be pulled out manually. [4] The images of three grades of nipple inversion are present in Fig. 1. Fig. 1 Three categories of nipple inversion grade I inverted nipple(a), grade II inverted nipple(b), grade III inverted nipple(c) Surgical interventions are the most effective treatments at present; however, injury to lactiferous ducts is inevitable in most surgical techniques [1, 5-10]. Some conservative nonoperative techniques have been developed in the last several years, such as a self retraction and suction device, but only mild cases of grade I are indicated. Several suspension and retraction devices have been reported in recent years [10, 11], and the effect was acceptable, but long-term results were not reported. To simplify the operation procedures and diminish the possibility of lactiferous duct injury, we developed a nipple retractor, which was made from a single-use syringe, to correct nipple inversion from 2003. The details of procedures and techniques are introduced in this paper, as well as a 10-year retrospective analysis. PMID- 27389408 TI - An additional method for the prevention of hypothermia in severely injured trauma patients. PMID- 27389410 TI - Improving mental health care transitions for children and youth: a protocol to implement and evaluate an emergency department clinical pathway. AB - BACKGROUND: While the emergency department (ED) is often a first point of entry for children and youth with mental health (MH) concerns, there is a limited capacity to respond to MH needs in this setting. Child MH systems are typically fragmented among multiple ministries, organizations, and providers. Communication among these groups is often poor, resulting in gaps, particularly in transitions of care, for this vulnerable population. The evidence-based Emergency Department Mental Health Clinical Pathway (EDMHCP) was created with two main goals: (1) to guide risk assessment and disposition decision-making for children and youth presenting to the ED with MH concerns and (2) to provide a streamlined transition to follow-up services with community MH agencies (CMHAs) and other providers. The purpose of this paper is to describe our study protocol to implement and evaluate the EDMHCP. METHODS/DESIGN: This mixed methods health services research project will involve implementation and evaluation of the EDMHCP in four exemplar ED-CMHA dyads. The Theoretical Domains Framework will be used to develop a tailored intervention strategy to implement the EDMHCP. A multiple baseline study design and interrupted time-series analysis will be used to determine if the EDMHCP has improved health care utilization, medical management of the MH problems, and health sector coordination. The primary process outcome will be the proportion of patients with MH-specific recommendations documented in the health record. The primary service outcome will be the proportion of patients receiving the EDMHCP recommended follow-up at 24-h or at 7 days. Data sources will include qualitative interviews, health record audits, administrative databases, and patient surveys. A concurrent process evaluation will be conducted to assess the degree of variability and fidelity in implementation across the sites. DISCUSSION: This paper presents a novel model for measuring the effects of the EDMHCP. Our development process will identify how the EDMHCP is best implemented among partner organizations to deliver evidence-based risk management of children and youth presenting with MH concerns. More broadly, it will contribute to the body of evidence supporting clinical pathway implementation within novel partnerships. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02590302 ). PMID- 27389412 TI - [Herpes zoster and postherpetic neuralgia]. AB - Herpes zoster develops by endogenous reactivation of varizella zoster virus (VZV). Incidence increases with age. Females are more frequently affected than males. The reactivation rate in seropositive individuals is about 20 %. After a short prodromal stage, herpetiform-grouped vesicles appear in segmental arrangement. Pain and paresthesia are typical zoster symptoms. Complications like bacterial superinfections, vasculopathy, paresis, and oculopathy may occur. During pregnancy herpes zoster is a threat for mother and child. Among elderly patients, cardiovascular risk is increased during the first week of herpes zoster infection. Postherpetic neuropathy is feared. Diagnosis can be made clinically and by the use of polymerase chain reaction. First-line treatment is systemic antiviral drug therapy with either acyclovir or brivudine. Adjuvant therapies consist of pain management and topical treatment. PMID- 27389411 TI - MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension. AB - Aims: Kv7.4, a voltage-dependent potassium channel expressed throughout the vasculature, controls arterial contraction and is compromised in hypertension by an unknown mechanism. MicroRNAs (miRs) are post-transcriptional regulators of protein production and are altered in disease states such as hypertension. We investigated whether miRs regulate Kv7.4 expression. Methods and results: In renal and mesenteric arteries (MAs) of the spontaneously hypertensive rat (SHR), Kv7.4 protein decreased compared with the normotensive (NT) rat without a decrease in KCNQ4 mRNA, inferring that Kv7.4 abundance was determined by post transcriptional regulation. In silico analysis of the 3' UTR of KCNQ4 revealed seed sequences for miR26a, miR133a, miR200b, miR153, miR214, miR218, and let-7d with quantitative polymerase chain reaction showing miR153 increased in those arteries from SHRs that exhibited decreased Kv7.4 levels. Luciferase reporter assays indicated a direct targeting effect of miR153 on the 3' UTR of KCNQ4. Introduction of high levels of miR153 to MAs increased vascular wall thickening and reduced Kv7.4 expression/Kv7 channel function compared with vessels receiving a non-targeting miR, providing a proof of concept of Kv7.4 regulation by miR153. Conclusion: This study is the first to define a role for aberrant miR153 contributing to the hypertensive state through targeting of KCNQ4 in an animal model of hypertension, raising the possibility of the use of miR153-related therapies in vascular disease. PMID- 27389413 TI - Algorithms to Identify Statin Intolerance in Medicare Administrative Claim Data. AB - PURPOSE: To compare characteristics of patients with possible statin intolerance identified using different claims-based algorithms versus patients with high adherence to statins. METHODS: We analyzed 134,863 Medicare beneficiaries initiating statins between 2007 and 2011. Statin intolerance and discontinuation, and high adherence to statins, defined by proportion of days covered >=80 %, were assessed during the 365 days following statin initiation. Definition 1 of statin intolerance included statin down-titration or discontinuation with ezetimibe initiation, having a claim for a rhabdomyolysis or antihyperlipidemic event followed by statin down-titration or discontinuation, or switching between >=3 types of statins. Definition 2 included beneficiaries who met Definition 1 and those who down-titrated statin intensity. We also analyzed beneficiaries who met Definition 2 of statin intolerance or discontinued statins. RESULTS: The prevalence of statin intolerance was 1.0 % (n = 1320) and 5.2 % (n = 6985) using Definitions 1 and 2, respectively. Overall, 45,266 (33.6 %) beneficiaries had statin intolerance by Definition 2 or discontinued statins and 55,990 (41.5 %) beneficiaries had high adherence to statins. Compared with beneficiaries with high adherence to statins, those with statin intolerance and who had statin intolerance or discontinued statins were more likely to be female versus male, and black, Hispanic or Asian versus white. The multivariable adjusted odds ratio for statin intolerance by Definitions 1 and 2 comparing patients initiating high versus low/moderate intensity statins were 2.82 (95%CI: 2.42-3.29), and 8.58 (8.07-9.12), respectively, and for statin intolerance or statin discontinuation was 2.35 (2.25-2.45). CONCLUSIONS: Definitions of statin intolerance presented herein can be applied to analyses using administrative claims data. PMID- 27389414 TI - Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens. AB - BACKGROUND: MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. METHODS: Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. RESULTS: Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and 0.20 Cqs accompanied by >94 % concordant single marker assignments for all four markers. In platform 2, the inter-site SD estimates were between 0.40 and 0.66 Cqs while the concordance for single marker assignments was >94 % for all four markers. The agreement reached between the two qPCR systems located in one site was 100 % for ERBB2, 96.9 % for ESR1, 97.2 % for PGR and 98.6 % for MKI67. RT-qPCR for individual markers was stable up to a 64-fold dilution for a typical clinical sample. There was no change in assay performance detected at the level of individual markers or subtypes after using different RNA isolation methods. The presence of up to 80 % of surrounding non-tumor tissue including in situ carcinoma did not affect the assay output. Sixteen out of 20 RNXtract eluates yielded more than 50 ng/MUl of RNA (average RNA output: 233 ng/MUl), whereas DNA contamination per sample was restricted to less than 15 ng/MUl. Median recovery rate of RNA extraction was 91.0 %. CONCLUSIONS: In this study the performance characteristics of MammaTyper were successfully validated. The various sources of analytical perturbations resulted in negligible variations in individual marker assessments. Therefore, MammaTyper may serve as a technical improvement to current standards for decentralized FFPE-based routine assessment of the commonly used breast cancer biomarkers and for molecular subtyping of breast cancer specimens. PMID- 27389415 TI - Asynchronous bilateral anastomosis site sigmoid colon cancer after ureterosigmoidostomy: a case report. AB - BACKGROUND: We present a case of asynchronously occurring adenocarcinomas 29 and 36 years after ureterosigmoidostomy for bladder cancer, respectively, at both anastomosis sites. CASE PRESENTATION: A colonoscopy that was performed on a 69 year-old man because of bloody stool and an elevated carcinoembryonic antigen (CEA) level revealed a polypoid lesion at the right ureterosigmoid anastomosis site 29 years after the patient's ureterosigmoidostomy. Endoscopic resection was performed, and the lesion was diagnosed as adenocarcinoma. Seven years later (36 years after ureterosigmoidostomy), an elevated lesion was detected at the left ureterosigmoid anastomosis site by colonoscopy performed after detection of high CEA levels. Biopsy revealed an adenocarcinoma that was immunohistologically positive for CDX2; sigmoidectomy and ureterectomy were subsequently performed. The pathological diagnosis of the second tumor was adenocarcinoma arising in the ureterosigmoid anastomosis site and invading the left ureter. CONCLUSIONS: Diligent long-term follow-up of patients who underwent ureterosigmoidostomy is essential. PMID- 27389416 TI - Serum albumin predicts survival in patients with hilar cholangiocarcinoma. AB - BACKGROUND AND AIMS: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. METHODS: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. RESULTS: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19-9 <=200 U/mL (P = 0.03), carcinoembryonic antigen <=10 ig/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks. CONCLUSION: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. PMID- 27389417 TI - Racial awakening: Epiphanies and encounters in Black racial identity. AB - OBJECTIVE: The current study was guided by Nigrescence theory (Cross, 1971, 1991) and explored the phenomenon of racial awakening or epiphanic experiences of Black adults. We were interested in describing the context and perceived outcomes of the epiphanies in participants' understanding of what it means to be Black. METHOD: Sixty-four adults participated in racial life narrative interviews. There was an equivalent number of men and women who participated from 4 sites: Australia, Bermuda, South Africa, and the United States. RESULTS: Findings from dimensional analysis highlight the turning points, triggers, and awakening or epiphanies in one's racial identity. Specifically, in this study racial awakening or increased awareness about the meaning of being Black was spurred by personal experiences and/or observations, education, and activism. Participants discussed increased racial activism, racial pride, and possible-selves after the process of racial awakening and continued exploration. Only 1 participant described disappointment and despair after a racial epiphany. CONCLUSIONS: Findings extend our understanding of the process in which people develop a sense of racial consciousness. Insights may help inform future researchers in terms of identifying racial awakening prototypic stories and counselors in terms of providing opportunities to assist individuals in the meaning-making process. (PsycINFO Database Record PMID- 27389419 TI - Pediatric autopsy case of asphyxia due to salmon egg (ikura) aspiration. AB - Here we report an autopsy case of asphyxia due to aspiration of a salmon egg (ikura) into the airway. The patient was a 19-month-old girl. During breakfast, she put salmon eggs into her mouth, and began to walk. She slipped, fell down, and collapsed. She was pronounced dead following 2 h of resuscitation. The body was autopsied 28 h after death. The gastric contents consisted of rice, orange sections, and white salmon eggs. The lungs were deeply congested and over inflated. In the right lung, areas of atelectasis in the upper and middle lobes were seen. A yellow salmon egg (8 mm in diameter) was found in the trachea. Although fish eggs are consumed throughout the world, reports of this sort are limited. The aspiration of fish eggs is under-acknowledged and underreported. The importance of preventive measures needs to be emphasized to parents and caregivers. PMID- 27389418 TI - Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota. AB - The symbiotic gut microbiota plays an important role in the development and homeostasis of the host organism. Its physiological, biochemical, behavioral, and communicative effects are mediated by multiple low molecular weight compounds. Recent data on small molecules produced by gut microbiota in mammalian organisms demonstrate the paramount importance of these biologically active molecules in terms of biology and medicine. Many of these molecules are pleiotropic mediators exerting effects on various tissues and organs. This review is focused on the functional roles of gaseous molecules that perform neuromediator and/or endocrine functions. The molecular mechanisms that underlie the effects of microbial fermentation-derived gaseous metabolites are not well understood. It is possible that these metabolites produce their effects via immunological, biochemical, and neuroendocrine mechanisms that involve endogenous and microbial modulators and transmitters; of considerable importance are also changes in epigenetic transcriptional factors, protein post-translational modification, lipid and mitochondrial metabolism, redox signaling, and ion channel/gap junction/transporter regulation. Recent findings have revealed that interactivity among such modulators/transmitters is a prerequisite for the ongoing dialog between microbial cells and host cells, including neurons. Using simple reliable methods for the detection and measurement of short-chain fatty acids (SCFAs) and small gaseous molecules in eukaryotic tissues and prokaryotic cells, selective inhibitors of enzymes that participate in their synthesis, as well as safe chemical and microbial donors of pleiotropic mediators and modulators of host intestinal microbial ecology, should enable us to apply these chemicals as novel therapeutics and medical research tools. PMID- 27389420 TI - Water-Induced Decoupling of Tracer and Electrochemical Oxygen Exchange Kinetics on Mixed Conducting Electrodes. AB - Isotope exchange depth profiling and electrochemical impedance spectroscopy are usually regarded as complementary tools for measuring the surface oxygen exchange activity of mixed conducting oxides, for example used in solid oxide fuel cell (SOFC) electrodes. Only very few studies compared electrical (k(q)) and tracer (k*) exchange coefficients of solid-gas interfaces measured under identical conditions. The 1:1 correlation between k(q) and k* often made is thus more an assumption than experimentally verified. In this study it is shown that the measured rates of electrical and tracer exchange of oxygen may strongly differ. Simultaneous acquisition of k(q) and k* on La0.6Sr0.4FeO3-delta and SrTi0.3Fe0.7O3-delta thin film electrodes revealed that k* > 100 k(q) in humid oxidizing ((16)O2 + H2(18)O) and humid reducing (H2 + H2(18)O) atmospheres. These results are explained by fast water adsorption and dissociation on surface oxygen vacancies, forming two surface hydroxyl groups. Hence, interpreting experimentally determined k* values in terms of electrochemically relevant oxygen exchange is not straightforward. PMID- 27389421 TI - Devising Self-Assembled-Monolayers for Surface-Enhanced Infrared Spectroscopy of pH-Driven Poly-l-lysine Conformational Changes. AB - Surface-enhanced infrared absorption spectroscopy (SEIRA) is applied to study protein conformational changes. In general, the appropriate functionalization of metal surfaces with biomolecules remains a challenge if the conformation and activity of the biomolecule shall be preserved. Here we present a SEIRA study to monitor pH-induced conformational changes of poly-l-lysine (PLL) covalently bound to a thin gold layer via self-assembled monolayers (SAMs). We demonstrate that the composition of the SAM is crucial. A SAM of 11-mercaptoundecanonic acid (MUA) can link PLL to the gold layer, but pH-driven conformational transitions were hindered compared to poly-l-lysine in solution. To address this problem, we devised a variety of SAMs, i.e., mixed SAMs of MUA with either octanethiol (OT) or 11-mercapto-1-undecanol (MUoL) and furthermore SAMs of MT(PEG)4 and NHS-PEG10k SH. These mixed SAMs modify the surface properties by changing the polarity and the morphology of the surface present to nearby PLL molecules. Our experiments reveal that mixed SAMs of MUA-MUoL and SAMs of NHS-PEG10k-SH-MT(PEG)4 are suitable to monitor pH-driven conformational changes of immobilized PLL. These SAMs might be applicable for chemoselective protein immobilization in general. PMID- 27389422 TI - Corrigendum to "Efficacy and tolerability of high-dose phenobarbital in children with focal seizures" [Brain Dev. 38 (2016) 414-418]. PMID- 27389424 TI - The Catalytic Mechanism of the Marine-Derived Macrocyclase PatGmac. AB - Cyclic peptides are a class of compounds with high therapeutic potential, possessing bioactivities including antitumor and antiviral (including anti-HIV). Despite their desirability, efficient design and production of these compounds has not been achieved to date. The catalytic mechanism of patellamide macrocyclization by the PatG macrocyclase domain has been computationally investigated by using quantum mechanics/molecular mechanics methodology, specifically ONIOM(M06/6-311++G(2d,2p):ff94//B3LYP/6-31G(d):ff94). The mechanism proposed herein begins with a proton transfer from Ser783 to His 618 and from the latter to Asp548. Nucleophilic attack of Ser783 on the substrate leads to the formation of an acyl-enzyme covalent complex. The leaving group Ala-Tyr-Asp-Gly (AYDG) of the substrate is protonated by the substrate's N terminus, leading to the breakage of the P1-P1' bond. Finally, the substrate's N terminus attacks the P1 residue, decomposing the acyl-enzyme complex forming the macrocycle. The formation and decomposition of the acyl-enzyme complex have the highest activation free energies (21.1 kcal mol(-1) and 19.8 kcal mol(-1) respectively), typical of serine proteases. Understanding the mechanism behind the macrocyclization of patellamides will be important to the application of the enzymes in the pharmaceutical and biotechnological industries. PMID- 27389425 TI - [Not Available]. PMID- 27389426 TI - [Not Available]. PMID- 27389428 TI - [Shared feeling of therapeutic deadlock in a psychiatric institution]. AB - Therapeutic deadlock in psychiatry is different from other medical disciplines: the feeling of deadlock is inherent to psychiatric care with chronic patients. It is present in different forms in institutional life where it is often shared. Reintroducing processes of speaking and thinking is therefore a priority to treat and relaunch a fixed psychological approach both on the part of the patient as well as the team. Reasserting the "psychoanalytical work as a group" can be a way of understanding situations of deadlock to find new ways of moving forward. PMID- 27389427 TI - [Is therapeutic deadlock inevitable?]. AB - Many long-term treatments appear to be an expression of therapeutic deadlock. The situation leads to a questioning of the concept of chronicity and the identification of the determining factors of situations which are apparently blocked, marked by the search for solutions taking a back seat to the taking of action. The interaction between patients' mental apparatus and the care apparatus lies at the heart of the question, interpreted from an institutional, collective and individual perspective, supported by the clinical and psychopathological approach, and the return to the prioritisation of the thought. PMID- 27389423 TI - Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors. AB - Stroke is the leading cause of disability in adults. Drug treatments that target stroke-induced pathological mechanisms and promote recovery are desperately needed. In the brain, an ischemic event triggers major inflammatory responses that are mediated by the resident microglial cells. In this review, we focus on the microglia activation after ischemic brain injury as a target of immunomodulatory therapeutics. We divide the microglia-mediated events following ischemic stroke into three categories: acute, subacute, and long-term events. This division encompasses the spatial and temporal dynamics of microglia as they participate in the pathophysiological changes that contribute to the symptoms and sequela of a stroke. The importance of Toll-like receptor (TLR) signaling in the outcomes of these pathophysiological changes is highlighted. Increasing evidence shows that microglia have a complex role in stroke pathophysiology, and they mediate both detrimental and beneficial effects on stroke outcome. So far, most of the pharmacological studies in experimental models of stroke have focused on neuroprotective strategies which are impractical for clinical applications. Post ischemic inflammation is long lasting and thus, could provide a therapeutic target for novel delayed drug treatment. However, more studies are needed to elucidate the role of microglia in the recovery process from an ischemic stroke and to evaluate the therapeutic potential of modulating post-ischemic inflammation to promote functional recovery. PMID- 27389429 TI - [Deadlock in a crisis unit, from helplessness to containment]. AB - The case of a young woman hospitalised in a psychiatric unit illustrates the deadlock which invades institutional life and presents possible solutions for overcoming it. This deadlock is in fact two-fold: that of the patient and that of the team caring for her. The patient's suffering is echoed by that of the caregivers, whose attempts to re-establish a bond, to give meaning to the procedures carried out, are lost in the meanders of an instability which has been reinforced over time by the pleasure of repetition. PMID- 27389430 TI - [The powerlessness of care: practice analysis as a way out]. AB - Some clinical situations, particularly associated with psychosis, push the teams in their entrenchment. Here, the caregiver's professional ideal is attacked from all sides in the face of the patient's resistance and denial, resulting in a feeling of therapeutic deadlock. The caregiving team, through discussion, will perhaps find a way out through the implementation of therapeutic strategies, encompassing a process of creation, consolidation and relaxing of a professional stance. PMID- 27389431 TI - [Cultivating confidence: a way forward in the face of therapeutic deadlocks]. AB - The aftercare centre is a therapeutic tool which sometimes enables situations of therapeutic deadlock to be overcome. By focusing on the long term, the patient is able to undertake a sustainable transformation of their relationship with themselves and with others. However, this challenging work cannot be carried out without a foundation of respect for the caregiving teams with regard to their therapeutic capacity as well as trust in their partners. PMID- 27389432 TI - [Taking the time to understand to move on from therapeutic deadlock]. AB - Psychotic symptoms of the type elementary phenomena and hallucinations can be pacified thanks to an individualised response. Teamwork is essential for fighting against the feeling of therapeutic deadlock. This article presents the therapeutic effects of the institutional care of a child with psychosis within a day hospital. PMID- 27389433 TI - [Optimising the stay of patients with a mental disorder in general medical or surgical units]. AB - The action research undertaken by health manager students at the Nice health manager training institution has helped to optimise the stay of patients with a mental disorder in general medical and surgical units. Based on the assessment of the training needs of caregivers working in these units, it enables the students to anticipate their future function. PMID- 27389434 TI - [Not Available]. PMID- 27389435 TI - Clinical Investigation and Patient Satisfaction of Short Implants Versus Longer Implants with Osteotome Sinus Floor Elevation in Atrophic Posterior Maxillae: A Pilot Randomized Trial. AB - PURPOSE: The aim of the study was to evaluate the clinical parameters and patient satisfaction of the treatments with short implants compared to longer implants with osteotome sinus floor elevation (OSFE) in atrophic posterior maxillae. MATERIALS AND METHOD: The patient data were retrieved from an ongoing randomized controlled trial (NCT02350075). Patients were randomly allocated into three groups: (group1: short-6 mm implant, group 2: short-8-mm implant with OSFE, group 3: standard-10 mm implant with OSFE). Early implant failure, complications, implant stability quotient (ISQ) and patient satisfaction by means of visual analogue scale (VAS) were evaluated. ANOVA analysis was performed for the data comparison. RESULTS: Fifty-six patients were enrolled in the present study. No implant loss was found by the end of the restoration placement. No significant difference of ISQ values was found among three groups at the time of implant surgery and impression taking (p = .67 and.54, respectively). VAS values regarding intraoperative vibratory sense in group 1 were significantly higher than those in group 3 (p = .01). CONCLUSION: All three treatments were safe in atrophic posterior maxilla (6 mm <= residual bone height < 8 mm). Patients were satisfied with all three treatments, while the malleting during the osteotome procedure could make patients feel uncomfortable. PMID- 27389436 TI - Participation in a randomised controlled feasibility study of a complex intervention for the management of the Respiratory Symptom Distress Cluster in lung cancer: patient, carer and research staff views. AB - This paper reports finding from a nested qualitative study designed to elicit the views and perceptions of those who participated in a randomised controlled feasibility trial testing a non-pharmacological intervention, Respiratory Distress Symptom Intervention (RDSI), for the management of the breathlessness cough-fatigue symptom cluster in lung cancer. Semi-structured interviews were conducted with 11 lung cancer patients, three caregivers and seven researchers involved in recruitment, consent, RDSI training and delivery and participant follow-up. Thematic analysis identified key considerations including: the importance of informed consent emphasising commitment to completion of paperwork and raising awareness of potential sensitivities relating to content of questionnaires; ensuring screening for the presence of symptoms reflects the language used by patients; appreciation of the commitment required from participants to learn intervention techniques and embed them as part of everyday life; conduct of interviews with patients who decline to participate; and conduct of serial interviews with those receiving RDSI to further inform its routine implementation into clinical practice. This study will inform the development of a fully powered follow-on trial testing the hypothesis that RDSI plus usual care is superior to usual care alone in the effective management of this symptom cluster in lung cancer. PMID- 27389437 TI - No increased risk of hospitalization for heart failure for patients treated with dipeptidyl peptidase-4 inhibitors in Taiwan. AB - BACKGROUND: Saxagliptin has been reported to be associated with an increased risk of hospitalization for heart failure (HF). The objective of this study was to test whether the increased risk is drug specific or a class effect for dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: Diabetic patients prescribed sitagliptin, saxagliptin, and vildagliptin between 2011 and 2013 were identified from Taiwan's National Health Insurance (NHI) claims database. The outcome of interest was the first hospitalization for HF. The patients were followed for one year from drug initiation to outcome occurrence, death, or study termination (December 31, 2013). A Cox proportional hazards regression model was used to calculate the hazard ratios (HR) and their 95% confidence intervals, using sitagliptin as the reference group. RESULTS: A total of 239,669 patients, including 159,330 sitagliptin, 38,561 saxagliptin, and 41,778 vildagliptin initiators, were included in the analysis. With a follow-up period ranging from 269days (vildagliptin) to 313days (sitagliptin), the crude incidence rate of HF was 2.77, 2.63, and 1.91 per 100 person-years for sitagliptin, saxagliptin, and vildagliptin, respectively. Saxagliptin had a similar risk (HR: 0.98, 95% CI: 0.91-1.06) to sitagliptin, while vildagliptin was associated with a lower risk of HF (HR: 0.85, 95% CI: 0.78-0.93). Auxiliary analyses using acarbose (n=130,800) as a reference group consistently showed no increased risk of HF associated with DDP-4 inhibitors. CONCLUSION: Three DPP-4 inhibitors studied seem to be safe regarding the risk of HF, while the reduced risk of vildagliptin might be a spurious association or a chance finding. PMID- 27389439 TI - MitraClip(r) and Amplatzer(r) cardiac plug implantation in a single procedure: A reasonable approach? AB - BACKGROUND: Percutaneous mitral valve repair using MitraClip(r) (MC) is a well established method for a subset of patients with severe mitral regurgitation (MR) and high risk for surgical intervention. Amplatzer(r) Cardiac Plug (ACP) occludes left atrial appendage and allows the discontinuation of oral anticoagulation and prevention of thromboembolic stroke. Due to the need for femoral and transseptal access in both procedures, a single approach could lead to minor risk of further complications and shorter cumulative intervention time. METHODS: We systematically analysed all four patients who underwent a combined procedure with MC and ACP in our heart-centre. All procedures were performed under fluoroscopic as well as echocardiographic guidance, and follow-up controls in a midterm period were carried out. RESULTS: In all patients (2 male/female; age 73-88years), MC (1 2 Clips) and ACP (size 18-28mm) were successfully implanted in one procedure (mean total time: 114+/-17min). At least moderate MR was achieved and two patients had no complications and therefore were discharged early. In a third patient, a dislocation of ACP occurred 2h after the implantation. The oldest patient developed a respiratory insufficiency due to cardiac decompensation and further complications. CONCLUSION: A combination of MC and ACP in a single procedure was feasible in this first case series of patients without a significant extension of procedure time. However, it might be important to select patients carefully. The location of optimal transseptal puncture may be challenging in regard to ACP placement, even in experienced hands and subsequent complications can occur. PMID- 27389438 TI - Association therapy with macitentan added to sildenafil in a thalassemic patient with pulmonary hypertension. PMID- 27389440 TI - Assessment of atrial fibrosis for the rhythm control of atrial fibrillation. AB - Rhythm control of atrial fibrillation (AF) remains challenging, with modest long term success rates. Atrial fibrosis has been associated with AF, but the clinical utility of assessment of this fibrosis has yet to be fully elucidated. In this paper we review the current state of understanding of the pathophysiology of atrial fibrosis in AF, and its impact upon the instigation and propagation of the arrhythmia. Fibrosis causes an increase in volume of dysfunctional extracellular matrix, and is associated with cellular alterations such as hypertrophy, apoptosis and membrane dysfunction within the atrial myocardium. In turn, these cause pathological alterations to atrial conduction, such as increased anisotropy, conduction block and re-entry, which can lead to AF. We review current methods of assessing atrial fibrosis and their impact upon the prediction of success of interventional rhythm control strategies such as ablation and cardioversion. We focus particularly on circulating biomarkers of fibrosis and scar formation; their role in the fibrotic process, and their value in the prediction of rhythm control success. We also review imaging and invasive electrocardiographic mapping techniques that may identify fibrosis, and again assess their potential predictive value. In this area there exist many unanswered questions, but further work will help to refine techniques to reliably identify and treat those patients who are most likely to benefit from rhythm control treatment strategies. PMID- 27389441 TI - The prognostic role of C-reactive protein after myocardial infarction in patients with normal or mildly impaired left ventricle systolic function. PMID- 27389443 TI - Left atrial strain: A useful index in atrial fibrillation. AB - Left atrial (LA) strain is a speckle tracking echocardiography (STE)-derived parameter applied to the analysis of chamber function that provides highly reproducible measures of LA deformation by a non-Doppler, angle-independent quantification. In recent years, data regarding accuracy and clinical application of LA strain are rapidly increasing. This review describes the main features of LA strain and examines the role of STE in the evaluation of various aspects of AF, as the risk of developing the arrhythmia in general population, the evaluation of LA fibrosis and LA impairment, the quantification of cardioembolic risk and of recurrence after cardioversion or ablation therapies. PMID- 27389442 TI - Depression as an independent prognostic factor for all-cause mortality after a hospital admission for worsening heart failure. AB - BACKGROUND: Depression is associated with increased mortality amongst patients with chronic heart failure (HF). Whether depression is an independent predictor of outcome in patients admitted for worsening of HF is unclear. METHODS: OPERA-HF is an observational study enrolling patients hospitalized with worsening HF. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D) questionnaire. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). Kaplan-Meier and Cox regression analyses were used to estimate the association between depression and all-cause mortality. RESULTS: Of 242 patients who completed the HADS-D questionnaire, 153, 54 and 35 patients had no (score 0-7), mild (score 8-10) or moderate-to-severe (score 11-21) depression, respectively. During follow-up, 35 patients died, with a median time follow-up of 360days amongst survivors (interquartile range, IQR 217-574days). In univariable analysis, moderate-to-severe depression was associated with an increased risk of death (HR: 4.9; 95% CI: 2.3 to 10.2; P<0.001) compared to no depression. Moderate to-severe depression also predicted all-cause mortality after controlling for age, CCI score, NYHA class IV, NT-proBNP and treatment with mineralocorticoid receptor antagonist, beta-blocker and diuretics (HR: 3.0; 95% CI: 1.3 to 7.0; P<0.05). CONCLUSIONS: Depression is strongly associated with an adverse outcome in the year following discharge after an admission to hospital for worsening HF. The association is only partly explained by the severity of HF or comorbidity. Further research is required to demonstrate whether recognition and treatment of depression improves patient outcomes. PMID- 27389444 TI - Implications of right ventricular septal pacing for medium-term prognosis: Propensity-matched analysis. AB - BACKGROUND: The effect of right ventricular (RV) septal pacing as opposed to RV apical pacing on prognosis in patients undergoing pacemaker implantation remains controversial. This study was performed to examine the clinical efficacy of RV septal pacing in a large cohort with medium-term follow-up and propensity-matched analysis. METHODS: A total of 982 consecutive patients with first pacemaker implantation between 2008 and 2013 at two centers in Japan (51.4% male, age 76.1+/-10.6years, 64.3% septal pacing, 94% preserved ejection fraction [EF]) were enrolled. Propensity matching successfully matched 446 patients into RV septal and apical pacing groups. The primary endpoint, a combination of all-cause death and hospitalization due to heart failure, was compared between the two groups. RESULTS: In the propensity-matched cohort, the primary endpoint was observed in 61 patients (13.7%) over a median follow-up period of 2.1years (interquartile range, 1.1-3.5years). The effects of septal pacing on prognosis were not statistically significant (hazard ratio [HR]=1.10, 95% confidence interval [CI]=0.60-2.04, P=0.752). No significant benefit of septal pacing was observed on all-cause death (HR=1.86, 95%CI=0.74-4.66, P=0.187) and heart failure hospitalization (HR=0.93, 95%CI=0.44-1.98, P=0.847) when assessed separately. CONCLUSION: Septal pacing did not show medium-term advantages in prognosis in this large-scale retrospective cohort study with propensity matching of patients with predominantly preserved EF. PMID- 27389445 TI - Relationship between different doses of beta-blockers and prognosis in elderly patients with reduced ejection fraction. AB - BACKGROUND: Beta-blockers (BBs) remain underused in elderly patients with reduced ejection fraction (REF). Our aim was to determine the prognostic impact of different doses of BB in this setting. METHODS AND RESULTS: A single-center observational study was conducted. Inclusion criteria were age>=75 and EF<=0.35. Six months after diagnosis, patients were divided into 3 groups depending on BB dose: no BB (NBB), low dose (<50% of the target dose) (LD), and high dose (>=50%) (HD). Two different analytical approaches were employed: multivariate Cox model and propensity-score (PS) matching. Outcomes were all-cause death and heart failure (HF) admission. We included 559 patients (134 NBB, 259 LD, and 166 HD) with median follow-up of 29.9months. There were 212 deaths (NBB: 70 (52.2%); LD: 94 (36.3%); and HD: 48 (28.9%)) and 171 HF admissions (NBB: 42 (31.3%); LD: 85 (32.8%); and HD: 44 (26.5%)). On multivariate analysis, both LD and HD were associated with improved survival, with no differences between them (HD vs. NBB=0.67, 95% CI=[0.46-0.98], p=0.037; HD vs. LD=1.03, 95% CI=[0.72-1.46], p=0.894; and LD vs. NBB=0.65, 95% CI=[0.48-0.90], p=0.009). However, BB therapy failed to show benefits in HF admissions (p=NS, for each comparison). PS-matched analysis included 198 patients, with similar results to those mentioned above. CONCLUSIONS: BB therapy was associated with a significant reduction in mortality among elderly patients with REF, regardless of dose. Nevertheless, it was not associated with a decrease in HF admissions. Further studies are needed to determine the optimal BB dose in these patients. PMID- 27389446 TI - Preservation of CGRP in myocardium attenuates development of cardiac dysfunction in diabetic rats. AB - BACKGROUND: Calcitonin gene-related peptide (CGRP) plays an important role in cardiovascular regulation, which was found reduced in serum of diabetic patients. To test the hypothesis that lack of CGRP in myocardium is associated with diabetic cardiac dysfunction, which may be improved by preservation of CGRP in diabetic rats. METHODS AND RESULTS: Diabetes was induced in male Sprague-Dawley rats by streptozotocin (50mg/kg). Two groups of the diabetic rats, one fed with standard laboratory chew and another with the laboratory food plus hot pepper (containing 0.0174% of capsaicin), to stimulate production and release of CGRP. Cardiac functions were evaluated by measurements of intraventricular pressures after 8weeks of development of diabetes. Transient receptor potential vanilloid type 1 (TRPV1), CGRP, beta1-adreneregic receptor and norepinephrine were analyzed. Significantly lower levels of TRPV1 and CGRP were detected in the thoracic dorsal root ganglia (DRG) and myocardium of the diabetic animals, along with significant decline in left ventricular systolic pressure (by 24%) and heart rate (by 25%) and increase of the end-diastolic pressure (by 83%) with obvious reduction of CGRP in the DRG, by 41%, the myocardium (by 30%) and the serum (by 20%). The cardiac performance, the TRPV1 and the CGRP in the diabetic animals fed with hot pepper were well preserved. No any significant change in beta1 adreneregic receptor and norepinephrine was detected. CONCLUSION: The findings may suggest a novel mechanism underlying diabetic cardiac dysfunctions via impairing TRPV1-CGRP pathway in myocardium. Preservation of the TRPV1-CGRP mechanism may prevent the development of cardiac dysfunction in diabetes. PMID- 27389447 TI - The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease. AB - With average life expectancy rising greatly, the incidence rate of arteriosclerotic cardiovascular disease (ASCVD) has significantly increased. The heart disease has now become the number one killer that threatens the global population health, the second is stroke. It will be of great significance to investigate the underlying pathophysiological mechanisms of ASCVD in order to promote effective prevention and treatment. The neuropeptide Y (NPY) has now been discovered for more than thirty years and is widely distributed in the central nervous system (CNS) and peripheral tissues. By combining with certain receptors, NPY performs a variety of physiological functions, including the regulation of food intake, cardiovascular effects, development, hormonal secretion, sexual behavior, biological rhythms, temperature and emotion. In ASCVD, increased peripheral NPY was involved in the pathophysiological process of atherosclerosis through affecting the vascular endothelial dysfunction, the formation of foam cells, the proliferation of vascular smooth muscle cells, the local inflammatory response of plaques and the activation and aggregation of platelets. Via central and/or the peripheral nervous system, increased NPY was associated with dyslipidemia, hypertension, obesity, diabetes, impaired glucose tolerance, and smoking which are all risk factors for ASCVD. In this review, we summarize the role of neuropeptide Y in the development of atherosclerotic cardiovascular disease. PMID- 27389448 TI - PCSK9 inhibitors may improve cardiovascular outcomes-Can we afford them? AB - BACKGROUND/OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can significantly lower low-density lipoprotein (LDL) cholesterol levels. Early evidence suggests that use of PCSK9i also reduces the incidence of major adverse cardiovascular events (MACE). Our objective was to determine preliminary economic implications of PCSK9i use to avoid MACE, based on the current data from major phase III clinical trials. METHODS: Outcome data of the 4529 patients treated with PCSK9i in the OSLER and ODYSSEY LONG TERM trials were collected from the published reports. Cost of preventing MACE was evaluated based on the existing outcome data and current US prices of PCSK9i. The pooled results were compared to the cost of curing Hepatitis C Virus (HCV) patients with novel HCV drugs. RESULTS: PCSK9i treatment in the OSLER and ODYSSEY LONG TERM trials resulted in prevention of 35 MACE in a total of 4903 patient-years: 8 cardiovascular deaths, 22 myocardial infarctions, 0 strokes and 5 unstable anginas. The cost of PCSK9i drugs consumed during the trial's current follow-up period, could have reached $70,172,141. Therefore, the cost of preventing any MACE would be $2,004,918 and the cost of preventing one death would be $8,777,518. These figures are one hundred fold higher than the cost of curing one HCV patient (~$84,000). CONCLUSIONS: According to the current published data, using PCSK9i to prevent MACE seems to be a very expensive strategy. If upcoming outcome trials will demonstrate similar results, it seems that at current prices, using these drugs would not be affordable for most healthcare systems. PMID- 27389450 TI - Early and late manifestation of Brugada syndrome ECG in arrhythmogenic cardiomyopathy. PMID- 27389449 TI - Assessment of myocardial function using MRI-based feature tracking in adults after atrial repair of transposition of the great arteries: Reference values and clinical utility. AB - BACKGROUND: Echocardiographic parameters of ventricular deformation of the systemic right ventricle (sRV) predict adverse clinical outcome in patients after atrial repair of transposition of the great arteries (TGA). We assessed myocardial deformation on cardiac MRI (CMR) and correlated these with clinical and conventional CMR parameters in TGA patients. METHODS: Retrospective analysis of CMR studies in 91 TGA patients (66% male; mean age 30.1+/-5.1years) at two tertiary adult congenital heart centers was conducted. Myocardial deformation was assessed by CMR-based feature tracking (FT), providing longitudinal (LS), radial (RS), and circumferential (CS) global strain for the sRV and the subpulmonary left ventricle. A subgroup of optimal TGA was defined (NYHA class I, NT-proBNP <300pg/ml, max. exercise work load >=100watt, no significant clinical events) as a reference cohort. RESULTS: There was a significant correlation between FT and conventional CMR parameters. Left ventricular ejection fraction (LVEF) correlated significantly with LV LS, RS, and CS (r between 0.24 and 0.34, p values between 0.03 and 0.005). sRVEF correlated with RV CS (r=0.56, p<0.001), and RV RS (r=0.32, p=0.007). QRS duration showed a negative correlation with RV CS (r= 0.53, p<0.001), LV RS (r=-0.34, p=0.008), and LV CS (r=-0.34, p=0.006). Reference values for the novel FT method in clinically optimal TGA patients are provided. CONCLUSION: Assessment of myocardial function using CMR-based FT is feasible in TGA patients. FT measurements related to important prognostic clinical parameters. Furthermore, we provide for the first time reference values for TGA patients in an optimal clinical status. PMID- 27389451 TI - Relationship between non-high-density lipoprotein cholesterol and the long-term mortality of cardiovascular diseases: NIPPON DATA 90. AB - BACKGROUND: Non-high-density lipoprotein (HDL) cholesterol level, generally less affected by fasting status or serum triglyceride levels, may be useful for predicting future cardiovascular events in daily clinical practice. This study aimed to investigate the role of non-HDL cholesterol in the development of fatal coronary events and stroke in the general Japanese population. METHODS AND RESULTS: From the NIPPON DATA 90 prospective cohort study, 8383 participants were followed up for 20years since 1990. After exclusion of 666 cases without lipid or covariates data, 561 cases who were 75years old or older, 274 cases with history of cardiovascular disease, and 181 cases with lipid-lowering treatment, 6701 participants were included in this analysis. Non-HDL cholesterol was defined as total cholesterol minus HDL cholesterol. Outcomes were death from coronary heart disease and stroke. During the period, 69 participants died from coronary heart disease and 112 from stroke. Compared with participants with non-HDL cholesterol level <3.9mmol/L, age- and sex-adjusted hazard ratios for mortality by coronary heart disease in those with non-HDL cholesterol levels of 3.9-4.3mmol/L, 4.4 4.8mmol/L and >=4.9mmol/L were 1.27 (95% confidence interval [CI] 0.65-2.49), 1.81 (95% CI 0.92-3.55) and 2.40 (95% CI 1.30-4.43), respectively (P trend=0.010). This association remained significant even after adjusting for other cardiovascular risk factors (P trend=0.010). There was no clear association between non-HDL cholesterol levels and mortality by stroke (P trend=0.052). CONCLUSIONS: Among the general Japanese population, non-HDL cholesterol levels were clearly associated with future mortality by coronary heart disease, but not by stroke. PMID- 27389452 TI - Prevalence of microplastics in the marine waters of Qatar. AB - Microplastics are firmly recognized as a ubiquitous and growing threat to marine biota and their associated marine habitats worldwide. The evidence of the prevalence of microplastics was documented for the first time in the marine waters of Qatar's Exclusive Economic Zone (EEZ). An optimized and validated protocol was developed for the extraction of microplastics from plankton-rich seawater samples without loss of microplastic debris present and characterized using Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy. In total 30 microplastic polymers have been identified with an average concentration of 0.71particlesm(-3) (range 0-3particlesm(-3)). Polypropylene, low density polyethylene, polyethylene, polystyrene, polyamide, polymethyl methacrylate, cellophane, and acrylonitrile butadiene styrene polymers were characterized with majority of the microplastics either granular shape, sizes ranging from 125MUm to 1.82mm or fibrous with sizes from 150MUm to 15.98mm. The microplastics are evident in areas where nearby anthropogenic activities, including oil-rig installations and shipping operations are present. PMID- 27389453 TI - Heavy metal distribution in organic and siliceous marine sponge tissues measured by square wave anodic stripping voltammetry. AB - May sponge spicules represent a "tank" to accumulate heavy metals? In this study we test this hypothesis determining the distribution of Cd, Pb and Cu concentrations between organic and siliceous tissues in Antarctic Demospongia (Sphaerotylus antarcticus, Kirkpatrikia coulmani and Haliclona sp.) and in the Mediterranean species Petrosia ficiformis. Results show that although, in these sponges, spicules represent about 80% of the mass content, the accumulation of pollutant is lower in the spicules than in the corresponding organic fraction. The contribution of tissues to the total sponge content of Cd, Pb and Cu is respectively 99%, 82% and 97% for Antarctic sponges and 96%, 95% and 96% for P. ficiformis, similar in polar and temperate organisms. These results pave the way to a better understanding of the role of marine sponges in uptaking heavy metals and to their possible use as monitor of marine ecosystems, recommend by the Water Framework Directive. PMID- 27389454 TI - Characterization of surface oil thickness distribution patterns observed during the Deepwater Horizon (MC-252) oil spill with aerial and satellite remote sensing. AB - Knowledge of the spatial distribution of oil thickness patterns within an on water spill is of obvious importance for immediate spill response activities as well as for subsequent evaluation of the spill impacts. For long-lasting continuous spills like the 2010 3-month Deepwater Horizon (DWH) event in the Gulf of Mexico, it is also important to identify changes in the dominant oil features through time. This study utilized very high resolution (<=5m) aerial and satellite imagery acquired during the DWH spill to evaluate the shape, size and thickness of surface oil features that dominated the DWH slick. Results indicate that outside of the immediate spill source region, oil distributions did not encompass a broad, varied range of thicknesses. Instead, the oil separated into four primary, distinct characterizations: 1) invisible surface films detectable only with Synthetic Aperture Radar imaging because of the decreased surface backscatter, 2) thicker sheen & rainbow areas (<0.005mm), 3) large regional areas of relatively thin, "metallic appearance" films (0.005-0.08mm), and 4) strands of thick, emulsified oil (>1mm) that were consistently hundreds of meters long but most commonly only 10-50m wide. Where present within the slick footprint, each of the three distinct visible oil thickness classes maintained its shape characteristics both spatially (at different distances from the source and in different portions of the slick), and temporally (from mid-May through July 2010). The region over the source site tended to contain a more continuous range of oil thicknesses, however, our results indicate that the continuous injection of subsurface dispersants starting in late May significantly altered (lowered) that range. In addition to characterizing the oil thickness distribution patterns through the timeline of one of the world's largest oil spills, this paper also details the extension of using high resolution aerial imagery to calibrate medium resolution satellite data sources such as USA's Thematic Mapper (30m) to provide larger-scale spatial views of major spills, and discusses implications for utilizing such data for oil spill characterizations and spill response. PMID- 27389455 TI - Metal contaminant fluxes across the sediment water interface. AB - To date, most estimates of contaminant fluxes across the sediment/water interface in risk assessments have been done using diffusive flux models. However, the reliability of these is limited as the overall flux from the sediment may have contributions caused by advection and bioturbation. We found through a comparison of modelled fluxes versus measured fluxes, that the methods Benthic Flux Chamber and surface leaching tests in a risk assessment context showed similar magnitude while calculated fluxes deviated at least by a factor of 100 from measured fluxes. This may be explained by the flux contribution in connection with bioturbation. The chamber-measured fluxes of copper were low compared to those of zinc and cobalt, but this is consistent with leaching tests that indicated copper to be more strongly bound. Risk assessments based on total concentrations may be misleading. PMID- 27389456 TI - Seasonal distribution and geochemical fractionation of heavy metals from surface sediment in a tropical estuary of Jeneberang River, Indonesia. AB - Lead (Pb) and zinc (Zn) concentrations from surface sediments were determined at 17 stations in riverine, estuarine, and marine environments during the wet and dry seasons. The geochemical fractionations were obtained by a sequential extraction procedure in five geochemical forms: exchangeable, bound to carbonate, iron-manganese oxide, organic, and residual fractions. The concentrations of Pb and Zn in the water were higher during the wet season than the dry season and higher in the riverine and marine samples than the estuarine samples. Following geochemical fractionation, the metals were found mainly in the residual fraction. The results indicated that the concentrations were influenced by season, with the sources of Pb and Zn derived mainly from rivers and natural sources. The contamination status in the estuary of the Jeneberang River was classified as weak to moderate pollution and the risk level to aquatic biota attributed was no risk to low risk. PMID- 27389457 TI - In situ soft sediment nutrient enrichment: A unified approach to eutrophication field experiments. AB - Adding fertiliser to sediments is an established way of studying the effects of eutrophication but a lack of consistent methodology, reporting on enrichment levels, or guidance on application rates precludes rigorous synthesis and meta analysis. We developed a simple enrichment technique then applied it to 28 sites across an intertidal sandflat. Fertiliser application rates of 150 and 600gNm(-2) resulted in pore water ammonium concentrations respectively 1-110 and 4 580*ambient, with greater elevations observed in deeper (5-7cm) than surface (0 2cm) sediments. These enrichment levels were similar to eutrophic estuaries and were maintained for at least seven weeks. The high between-site variability could be partially explained by the sedimentary environment and macrofaunal community (42%), but only at the high application rate. We suggest future enrichment studies should be conducted in situ across large environmental gradients to incorporate real world complexity and increase generality of conclusions. PMID- 27389458 TI - Priority pesticides in sediments of European coastal lagoons: A review. AB - This review summarizes the legislation applied to pesticides and highlights the physicochemical properties of the past and recently listed PPs under Water Framework Directive (WFD). It reports important information regarding the analysis, occurrence and long-term screening of PPs in sediments of European coastal lagoons. Among the entire list of PPs, those analyzed have been the organochloride insecticides, such as lindane, hexachlorobenzene and DDT. Although flood events pointed to the possible redistribution of pesticides, which may increase under climate change conditions, few studies are available concerning PPs screening in sediments of European coastal lagoons. Data is scarce not only in terms of the number of listed PPs that have been analyzed but also in terms of their long-term screening. This lack of data on PP concentrations is probably a consequence of the fact that less importance is given to the sediments contamination/quality. PMID- 27389459 TI - Assessing fuel spill risks in polar waters: Temporal dynamics and behaviour of hydrocarbons from Antarctic diesel, marine gas oil and residual fuel oil. AB - As part of risk assessment of fuel oil spills in Antarctic and subantarctic waters, this study describes partitioning of hydrocarbons from three fuels (Special Antarctic Blend diesel, SAB; marine gas oil, MGO; and intermediate grade fuel oil, IFO 180) into seawater at 0 and 5 degrees C and subsequent depletion over 7days. Initial total hydrocarbon content (THC) of water accommodated fraction (WAF) in seawater was highest for SAB. Rates of THC loss and proportions in equivalent carbon number fractions differed between fuels and over time. THC was most persistent in IFO 180 WAFs and most rapidly depleted in MGO WAF, with depletion for SAB WAF strongly affected by temperature. Concentration and composition remained proportionate in dilution series over time. This study significantly enhances our understanding of fuel behaviour in Antarctic and subantarctic waters, enabling improved predictions for estimates of sensitivities of marine organisms to toxic contaminants from fuels in the region. PMID- 27389460 TI - Debris size and buoyancy influence the dispersal distance of stranded litter. AB - Recent at sea surveys of floating macro-debris in the southeast Atlantic Ocean found that debris increases in size with distance from shore, suggesting that many smaller items, which dominate litter close to urban source areas, sink before dispersing far into the ocean. We test whether this pattern is evident in beach litter in the same region. Freshly stranded beach litter was collected at increasing distances (0km, 100km, 200km and 2800km) from Cape Town, a major urban litter source. Mean size and buoyancy of litter items increased significantly with distance from Cape Town. Size-specific sedimentation due to the ballasting effect of biofouling is a plausible explanation for the disappearance of smaller, less buoyant items. Our results provide further evidence that many low buoyancy items sink and support the hypothesis that size and buoyancy are strong predictors of dispersal distance for floating debris. PMID- 27389462 TI - Future Papers. PMID- 27389461 TI - Fate, behaviour and weathering of priority HNS in the marine environment: An online tool. AB - Literature data and data obtained with modelling tools were compiled to derive the physicochemical behaviour of 24 priority Hazardous and Noxious Substances (HNS), as a proxy to improve environmental, public health and political issues in relation to HNS spills. Parameters that rule the HNS behaviour in water and those that determine their distribution and persistence in the environment, such as fugacity, physicochemical degradation, biodegradation, bioaccumulation/biotransformation and aquatic toxicity, were selected. Data systematized and produced in the frame of the Arcopol Platform project was made available through a public database (http://www.ciimar.up.pt/hns/substances.php). This tool is expected to assist stakeholders involved in HNS spills preparedness and response, policy makers and legislators, as well as to contribute to a current picture of the scientific knowledge on the fate, behaviour, weathering and toxicity of priority HNS, being essential to support future improvements in maritime safety and coastal pollution response before, during and after spill incidents. PMID- 27389463 TI - Incident Management Systems and Building Emergency Management Capacity during the 2014-2016 Ebola Epidemic - Liberia, Sierra Leone, and Guinea. AB - Establishing a functional incident management system (IMS) is important in the management of public health emergencies. In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC established the Emergency Management Development Team (EMDT) to coordinate technical assistance for developing emergency management capacity in Guinea, Liberia, and Sierra Leone. EMDT staff, deployed staff, and partners supported each country to develop response goals and objectives, identify gaps in response capabilities, and determine strategies for coordinating response activities. To monitor key programmatic milestones and assess changes in emergency management and response capacities over time, EMDT implemented three data collection methods in country: coordination calls, weekly written situation reports, and an emergency management dashboard tool. On the basis of the information collected, EMDT observed improvements in emergency management capacity over time in all three countries. The collaborations in each country yielded IMS structures that streamlined response and laid the foundation for long-term emergency management programs.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west africa/partners.html). PMID- 27389464 TI - The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages. AB - Sorting of luminal and membrane proteins into phagosomes is critical for the immune function of this organelle. However, little is known about the mechanisms that contribute to the spatiotemporal regulation of this process. Here, we investigated the role of the proneurotrophin receptor sortilin during phagosome maturation and mycobacterial killing. We show that this receptor is acquired by mycobacteria-containing phagosomes via interactions with the adaptor proteins AP 1 and GGAs. Interestingly, the phagosomal association of sortilin is critical for the delivery of acid sphingomyelinase (ASMase) and required for efficient phagosome maturation. Macrophages from Sort1(-/-) mice are less efficient in restricting the growth of Mycobacterium bovis BCG and M. tuberculosis. In vivo, Sort1(-/-) mice showed a substantial increase in cellular infiltration of neutrophils in their lungs and higher bacterial burden after infection with M. tuberculosis. Altogether, sortilin defines a pathway required for optimal intracellular mycobacteria control and lung inflammation in vivo. PMID- 27389465 TI - Probiotic activity of Enterococcus faecalis CECT7121: effects on mucosal immunity and intestinal epithelial cells. AB - AIMS: To analyse the effect of Enterococcus faecalis CECT7121 on intestinal epithelial cells (IECs) and its effects on the mucosal immune response. METHODS AND RESULTS: Enterococcus faecalis CECT7121 showed a high adhesion capacity to completely and heterogeneously differentiated human intestinal epithelial cell line (Caco-2 cells). In addition, the contact of this bacterium with Caco-2 cells did not induce inflammatory chemokines (IL-8 and CCL-20). The presence of IgA(+) and IL-6(+) cells in the small intestine, as well as the production of inflammatory cytokines (TNFalpha, IL-6 and IL-12) in the gut, was determined after intragastric inoculation of Ent. faecalis CECT7121 in BALB/c mice. The administration of Ent. faecalis CECT7121 increased the number of IgA(+) cells in the intestinal lamina propria without modifying the percentage of IL-6(+) cells. No differences were observed in the cytokines measured in the intestinal extracts between probiotic-treated and control mice. CONCLUSIONS: Enterococcus faecalis CECT7121 stimulates local mucosal immunity and adheres to IECs without inducing inflammatory signals. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results indicate that, apart from its already reported systemic immune activity, Ent. faecalis CECT7121 has a modulatory effect at a local level. PMID- 27389466 TI - Educational attainment, labour market position and mental ill health as pathways from adversities in adolescence to disability pension in early adulthood: A Finnish cohort study using register data. AB - BACKGROUND: We investigated whether social adversities (parents' receipt of income support and care placement) in adolescence were associated with the receipt of work disability pension (DP) in early adulthood. A further aim was to examine whether and to what extent individual educational attainment, labour market position and mental disorders during the period of transition to adulthood operate as underlying mechanisms in this relationship. METHODS: This was a nationwide cohort study of a 60% representative sample of Finnish young adults born between 1983 and 1985 with no prior DP at entry to the study ( N=116,788). Data from several nationwide registers were used with a follow-up time from 2004 to 2010. The age range of the cohort was 19-21 years at the beginning of the follow-up period. Hazards ratios (HRs) with 95% confidence intervals (CIs) were calculated using a Cox regression. Mediation analyses for educational attainment, labour market position and purchases of psychotropic drugs were performed. RESULTS: A total of 1597 (1.37%) people were granted a DP during the follow-up period of 687,429 years at risk. After adjustment for mediators, the HR (95% CI) of DP for those whose parents had received income support was 1.36 (1.21-1.53) for men and 1.21 (1.07-1.36) for women. The corresponding figures for those with a history of care placement were 1.23 (1.00-1.51) and 1.58 (1.29-1.92), respectively. CONCLUSIONS: Social adversities in adolescence increase the risk of DP in early adulthood. The intergenerational social determination of disability could be addressed through interventions promoting mental health and improving educational and employment opportunities for young people. PMID- 27389467 TI - Measuring quality of life in acute myeloid leukemia: limitations and future directions. PMID- 27389468 TI - Purification and characterization of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) from pea seeds. AB - Glyceraldehyde-3-phosphate dehydrogenase [GAPDH, NAD + oxidoreductase (phosphorylating) 1.2.1.12] catalyzes the conversion of glyceraldehyde-3 phosphate to 1,3-bisphosphoglycerate coupled with the reduction of NAD(+) to NADH. In addition to its role in glycolysis, this enzyme has numerous alternate functions, in both prokaryotes and eukaryotes. In plants, additional functions have been reported from multiple species including Pisum sativum. A recent study has identified that GAPDH may play an important role in seed ageing and programmed cell death. Despite this the existing purification protocols are almost 40 years old, and only partial characterization of the enzyme has been reported. In the current study, we report a modified method for purification of enzymatically active pea seed GAPDH along with the characterization of the enzyme. Using 2D gel electrophoresis our study also demonstrates that pea seeds contain four isoforms of NAD(+) dependent GAPDH. PMID- 27389469 TI - Expression, purification and initial characterization of a novel recombinant antimicrobial peptide Mytichitin-A in Pichia pastoris. AB - Mytichitin-A is an antimicrobial peptide isolated from the serum of Mytilus coruscus and is reported to inhibit bacterial growth as tested on several Gram positive bacteria. To produce large quantity of Mytichitin-A to further investigate its biological activity, nucleotide sequence encoding a recombinant 6 * His-Mytichitin-A (rMytichitin-A) peptide was synthesized and inserted into the inducible yeast expression vector pPICZalphaA. With the availability of such an expression vector called pPICZalphaA-Mytichitin-A, we transformed Pichia pastoris GS115 cells with a SacI-linearized pPICZalphaA-Mytichitin-A by electroporation. Transgenic strains secreting rMytichitin-A with a molecular weight of approximate 10 KDa as expected were obtained. The optimal culture condition for rMytichitin-A expression was determined to be 1.0% methanol induction, 96 h incubation at 28 degrees C and the amount of rMytichitin-A reached 45.5 MUg/ml. The percentage of rMytichitin-A was estimated to be 73.6% of the total protein. After rMytichitin-A was purified using nickel ions affinity chromatography, approximate 9.1 mg pure rMytichitin-A was obtained from 500 ml of cell culture medium with 97.8% purity. More importantly, both the culture supernatant and purified rMytichitin-A inhibited the growth of Gram-positive bacteria, especially Staphylococcus aureus and Bacillus subtilis with a minimum inhibition concentration of as low as 31 and 48 MUg/ml, respectively. Differently from the native protein, however, the rMytichitin-A is not active against Gram-negative bacteria. Taken together, this is the first report on the heterologous expression of Mytichitin-A in P. pastoris. Our study showed that P. pastoris is an effective expression system for producing large quantities of biologically active Mytichitin-A for both research and application purposes. PMID- 27389470 TI - Does a 3D Image Improve Laparoscopic Motor Skills? AB - AIM: To quantitatively determine whether a three-dimensional (3D) image improves laparoscopic performance compared with a two-dimensional (2D) image. METHOD: This is a prospective study with two groups of participants: novices (5) and experts (5). Individuals within each group undertook a validated laparoscopic task on a box simulator, alternating between 2D and a 3D laparoscopic image until they had repeated the task five times with each imaging modality. A dedicated motion capture camera was used to determine the time taken to complete the task (seconds) and instrument distance traveled (meters). RESULTS: Among the experts, the mean time taken to perform the task on the 3D image was significantly quicker than on the 2D image, 40.2 seconds versus 51.2 seconds, P < .0001. Among the novices, the mean task time again was significantly quicker on the 3D image, 56.4 seconds versus 82.7 seconds, P < .0001. There was no significant difference in the mean time it took a novice to perform the task using a 3D camera compared with an expert on a 2D camera, 56.4 seconds versus 51.3 seconds, P = .3341. CONCLUSION: The use of a 3D image confers a significant performance advantage over a 2D camera in quantitatively measured laparoscopic skills for both experts and novices. The use of a 3D image appears to improve a novice's performance to the extent that it is not statistically different from an expert using a 2D image. PMID- 27389471 TI - Corrigendum: Molecular orbital analysis of the hydrogen bonded water dimer. PMID- 27389472 TI - Functional analysis and intervention for perseverative verbal behaviour of an older adult with traumatic brain injury. AB - OBJECTIVE: A functional analysis of behaviour was conducted to determine the controlling variables related to the perseverative verbal behaviour (PBV) of a 60 year-old female with a long-standing traumatic brain injury receiving educational assistance. METHOD: Functional analyses (FA) of antecedent and consequent conditions related to PCB were conducted to determine controlling influence of: (a) content of verbal interaction and, (b) social reinforcement. After isolating the controlling variables, the functioned-based intervention was implemented in 60 minute tutoring sessions. A reversal condition was used to demonstrate experimental control of the behavior during tutoring sessions. RESULTS: PVB which occurred in the context of tutoring for an undergraduate course significantly interfered with the delivery of instruction. Multiple replications of the functional relation between social reinforcement and PVB duration was demonstrated using an A-B-A-B reversal design during functional analysis and tutoring conditions. PVB markedly declined, but did not extinguish over the course of weekly tutoring (extinction) sessions, most likely due to 'bootleg reinforcement' occurring in other situations. CONCLUSIONS: Results indicate that perseverative verbal behaviour following closed head injury may be strongly influenced by the social contingencies operating in various contexts and is amenable to applied behaviour analysis interventions. PMID- 27389473 TI - Deoxynivalenol induced mouse skin tumor initiation: Elucidation of molecular mechanisms in human HaCaT keratinocytes. AB - Among food contaminants, mycotoxins are toxic to both human and animal health. Our prior studies suggest that Deoxynivalenol (DON), a mycotoxin, behaves as a tumor promoter by inducing edema, hyperplasia, ODC activity and activation of MAPK's in mouse skin. In this study, topical application of DON, 336 and 672 nmol significantly enhanced ROS levels, DNA damage and apoptosis with concomitant downregulation of Ki-67, cyclin D, cyclin E, cyclin A and cyclin-dependent kinases (CDK4 and CDK2) thereby resulting in tumor initiation in mouse skin. Further, the elucidation of molecular mechanisms of tumor initiation by DON (0.42 3.37 nmol/ml) in HaCaT keratinocytes, revealed (i) enhanced ROS generation with cell cycle phase arrest in G0/G1 phase, (ii) increase in levels of 8-OxoG (6-24 hr) and gammaH2AX protein, (iii) significant enhancement in oxidative stress marker enzymes LPO, GSH, GR with concomitant decrease in antioxidant enzymes catalase, GPx, GST, SOD and mitochondrial membrane potential after DON (1.68 nmol) treatment, (iv) suppression of Nrf2 translocation to nucleus, enhanced phosphorylation with subsequent activation ERK1/2, p38 and JNK MAPK's following DON (1.68 nmol) treatment, (v) overexpression of c-jun, c-fos proteins, upregulation of Bax along with downregulation of Bcl-2 proteins, (vi) increase in cytochrome-c, caspase-9, caspase-3 and poly ADP ribose polymerase levels leads to apoptosis. Pretreatment of superoxide dismutase, mannitol and ethanol to HaCaT cells resulted in significant reduction in ROS levels and apoptosis indicating the role of superoxide and hydroxyl radicals in DON induced apoptosis as an early event and skin tumor initiation as a late event. PMID- 27389474 TI - Genetic determinants of lactococcal C2viruses for host infection and their role in phage evolution. AB - Lactococcus lactis is an industrial starter culture used for the production of fermented dairy products. Pip (phage infection protein) bacteriophage-insensitive mutant (BIM) L. lactis DGCC11032 was isolated following challenge of parental strain DGCC7271 with C2viruses. Over a period of industrial use, phages infecting DGCC11032 were isolated from industrial whey samples and identified as C2viruses. Although Pip is reported to be the receptor for many C2viruses including species type phage c2, a similar cell-membrane-associated protein, YjaE, was recently reported as the receptor for C2virus bIL67. Characterization of DGCC7271 BIMs following challenge with phage capable of infecting DGCC11032 identified mutations in yjaE, confirming YjaE to be necessary for infection. DGCC7271 YjaE mutants remained sensitive to the phages used to generate pip variant DGCC11032, indicating a distinction in host phage determinants. We will refer to C2viruses requiring Pip as c2-type andC2viruses that require YjaE as bIL67-type. Genomic comparisons of two c2-type phages unable to infect pip mutant DGCC11032 and four bIL67-type phages isolated on DGCC11032 confirmed the segregation of each group based on resemblance to prototypical phages c2 and bIL67, respectively. The distinguishing feature is linked to three contiguous late-expressed genes: l14-15 16 (c2) and ORF34-35-36 (bIL67). Phage recombinants in which the c2-like l14-15 16 homologue gene set was exchanged with corresponding bIL67 genes ORF34-35-36 were capable of infecting a pip mutated host. Together, these results correlate the phage genes corresponding to l14-15-16 (c2) and ORF34-35-36 (bIL67) to host lactococcal phage determinants Pip and YjaE, respectively. PMID- 27389477 TI - From 1D to 3D - macroscopic nanowire aerogel monoliths. AB - Here we present a strategy to assemble one-dimensional nanostructures into a three-dimensional architecture with macroscopic size. With the assistance of centrifugation, we successfully gel ultrathin W18O49 nanowires with diameters of 1 to 2 nm and aspect ratios larger than 100 into 3D networks, which are transformed into monolithic aerogels by supercritical drying. PMID- 27389476 TI - TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus. AB - Influenza A and B viruses show clear differences in their host specificity and pandemic potential. Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo. IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage. In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed. The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice. The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo. PMID- 27389475 TI - Cetuximab and Radiotherapy in Laryngeal Preservation for Cancers of the Larynx and Hypopharynx: A Secondary Analysis of a Randomized Clinical Trial. AB - IMPORTANCE: The appropriate use of surgery or radiotherapy-based approaches for organ preservation has been the subject of much debate. Unfortunately, there has been a lack of improvement in overall survival for patients with laryngeal carcinoma in the last 30 years. OBJECTIVE: To assess the rates of laryngeal preservation and laryngectomy-free survival in patients receiving cetuximab and radiotherapy (CRT) and patients receiving radiotherapy alone. DESIGN, SETTING, AND PARTICIPANTS: Patients were enrolled in a multicenter, open-label, stratified, randomized, phase 3 study from April 1, 1999, through March 31, 2002, from 73 centers in the United States and 14 other countries. A secondary subgroup analysis of patients with hypopharyngeal and laryngeal carcinoma was undertaken. Rates of laryngeal preservation and laryngectomy-free survival were estimated by the Kaplan-Meier method. The hazard ratios (HRs) were calculated using a Cox proportional hazards regression model. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer core questionnaire and head and neck module. MAIN OUTCOMES AND MEASURES: Laryngeal preservation and laryngectomy-free survival. RESULTS: Of the 424 patients included in the trial, 168 treated patients with cancer of the larynx or hypopharynx were included in this analysis (90 in the CRT group and 78 in the radiotherapy alone group). The median (range) age of the patients was 59 (40-80) years in the CRT group and 61 (35-81) years in the radiotherapy alone group. In the CRT group, 72 patients (80.0%) were male and 18 (20.0%) were female. In the radiotherapy alone group, 62 (79.5%) were male and 16 (20.5%) were female. The rates of laryngeal preservation at 2 years were 87.9% for CRT vs 85.7% for radiotherapy alone, with an HR of 0.57 (95% CI, 0.23-1.42; P = .22). Similarly, the HR for laryngectomy-free survival comparing CRT vs radiotherapy alone was 0.78 (95% CI, 0.54-1.11; P = .17). This study was not powered to assess organ preservation. Median overall survival was 27 (95% CI, 20-45) vs 21 (95% CI, 17-35) months for the CRT and radiotherapy alone groups, respectively, with an HR of 0.87 (95% CI, 0.60-1.27). No differences between treatments were reported regarding overall quality of life, need for a feeding tube, or speech. CONCLUSIONS AND RELEVANCE: The results of a possible cetuximab-related laryngeal preservation benefit for patients with hypopharyngeal or laryngeal cancer are intriguing; these results need to be interpreted in the context of a retrospective subset analysis with limited sample size. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00004227. PMID- 27389478 TI - On Freud's theory of law and religion. AB - This paper is a critical engagement with Freud's anthropological theory of the origins of law and religion, which Freud developed as his representation and development of the Oedipal myth. Freud's mythology, it is argued, is the theoretical result of the essentially narrative nature of psychoanalytical praxis. Freud's myth, especially its treatment of patricide as the original sin, is seen to be a displacement of the biblical myth of fratricide as the original sin. It is argued that the biblical myth is more coherent than Freud's myth, and that it corresponds to the reality of the human condition better than Freud's myth. The paper concludes with the suggestion that the acceptance of the biblical myth in place of Freud's does not necessarily entail a rejection of psychoanalysis as a praxis. PMID- 27389479 TI - Orthostatic hypotension: pathophysiology, assessment, treatment and the paradox of supine hypertension. AB - Both hypertension and orthostatic hypotension (OH) are strongly age-associated and are common management problems in older people. However, unlike hypertension, management of OH has unique challenges with few well-established treatments. Not infrequently, they both coexist, further compounding the management. This review provides comprehensive information on OH, including pathophysiology, diagnostic workup and treatment, with a view to provide a practical guide to its management. Special references are made to patients with supine hypertension and postprandial hypotension and older hypertensive patients. PMID- 27389481 TI - Formation of CaB6 in the thermal decomposition of the hydrogen storage material Ca(BH4)2. AB - Using a combination of high resolution X-ray powder diffraction and X-ray Raman scattering spectroscopy at the B K- and Ca L2,3-edges, we analyzed the reaction products of Ca(BH4)2 after annealing at 350 degrees C and 400 degrees C under vacuum conditions. We observed the formation of nanocrystalline/amorphous CaB6 mainly and found only small contributions from amorphous B for annealing times larger than 2 h. For short annealing times of 0.5 h at 400 degrees C we observed neither CaB12H12 nor CaB6. The results indicate a reaction pathway in which Ca(BH4)2 decomposes to B and CaH2 and finally reacts to form CaB6. These findings confirm the potential of using Ca(BH4)2 as a hydrogen storage medium and imply the desired cycling capabilities for achieving high-density hydrogen storage materials. PMID- 27389480 TI - Bio-inspired sensitive and reversible mechanochromisms via strain-dependent cracks and folds. AB - A number of marine organisms use muscle-controlled surface structures to achieve rapid changes in colour and transparency with outstanding reversibility. Inspired by these display tactics, we develop analogous deformation-controlled surface engineering approaches via strain-dependent cracks and folds to realize the following four mechanochromic devices: (1) transparency change mechanochromism (TCM), (2) luminescent mechanochromism (LM), (3) colour alteration mechanochromism (CAM) and (4) encryption mechanochromism (EM). These devices are based on a simple bilayer system that exhibits a broad range of mechanochromic behaviours with high sensitivity and reversibility. The TCM device can reversibly switch between transparent and opaque states. The LM can emit intensive fluorescence as stretched with very high strain sensitivity. The CAM can turn fluorescence from green to yellow to orange as stretched within 20% strain. The EM device can reversibly reveal and conceal any desirable patterns. PMID- 27389482 TI - Oxygen activation and catalytic aerobic oxidation by Mo(iv)/(vi) complexes with functionalized iminophenolate ligands. AB - Synthesis of molybdenum(vi) dioxido complexes 1-3, coordinated by one or two functionalized iminophenolate ligands HL1 or HL2, bearing a donor atom side chain or a phenyl substituent, respectively, allowed for systematic investigation of the oxygen atom transfer (OAT) reactivity of such complexes towards phosphanes. Depending on stoichiometry and employed phosphane (PMe3 or PPh3), different molybdenum(iv) and molybdenum(v) complexes 4-7 were obtained. Whereas molybdenum(iv) complexes 4 and 5, bearing a terminal PMe3 ligand, readily reacted with molecular O2 to form oxido peroxido complexes 8 and 9, phosphane free MU oxido bridged dinuclear molybdenum(v) complexes 6 and 7 proved to be stable towards oxidation with molecular O2 under ambient conditions. Single-crystal X ray diffraction analyses revealed different isomeric structures in the solid state for dioxido complexes 1 and 2 in comparison with oxido phosphane complex 5, dinuclear oxido MU-oxido complex 6 and oxido peroxido complexes 8 and 9, pointing towards an isomeric rearrangement during OAT. Compounds 1 and 2 were furthermore tested for their ability to catalyze the aerobic oxidation of PMe3 and PPh3. A significant difference in catalytic activity has been observed in the oxidation of PMe3, where complex 1 bearing donor atom functionalized ligands led to higher conversion and selectivity than complex 2 coordinated by phenyl iminophenolate ligands. In the oxidation of PPh3, complex 2 leads to higher conversion compared to 1. In a control experiment, phenyl-based dinuclear MU-oxido complex 7, derived from complex 2, was found to be catalytically active, which suggests a lower energy barrier for disproportionation into [MoO(L)2] and [MoO2(L)2] in comparison with methoxypropylene based compound 6, a prerequisite for subsequent reactivity toward molecular O2. PMID- 27389483 TI - Surgical removal of brachiocephalic junction endovascular stent migrated to the right atrium in a high risk patient. PMID- 27389485 TI - New mAb therapies in multiple myeloma: interference with blood transfusion compatibility testing. AB - PURPOSE OF REVIEW: Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients. RECENT FINDINGS: CD38 is weakly expressed on human erythrocytes. Since the first reports on the interference, different solutions have been reported, including the neutralization of anti-CD38 mAbs in plasma by sCD38 or antiidiotype antibodies, CD38 depletion of RBCs using dithiothreitol or cord blood test cells, and transfusion of extensively typed RBCs. SUMMARY: All methods have (dis)advantages, and it depends on the facilities of the immunohematology laboratory what strategy to choose. As the selection of suitable RBC units can be seriously delayed, hospitals should have protocols to communicate this interference with patients, laboratories, and physicians in a timely manner. As CD38 antibodies may also have a role in the treatment of diseases beyond hematological malignancies, chances are high that health professionals will encounter this issue in the nearby future. PMID- 27389486 TI - Donor deferral policies for men who have sex with men: where are we today? AB - PURPOSE OF REVIEW: The review summarizes recent publications on the contentious issue of donor deferral criterion for men who have sex with men (MSM). RECENT FINDINGS: Recent studies from the United States and China demonstrated that MSM is still a frequent risk factor for HIV-positive donors. Noncompliance is an important factor in the overall risk of HIV transmission but does not appear to be affected by the length of the deferral period. A major US study found a 2.6% noncompliance rate with the current indefinite deferral for MSM; similar or lower rates were found in other jurisdictions with shorter deferral periods. Several countries have had a defined deferral period of 1 year or 5 years in place long enough to determine that increases in HIV-positive cases predicted by modeling studies did not actually occur, suggesting that the assumptions made in these models are overly conservative. SUMMARY: In summary, MSM eligibility policies are slowly changing around the world, with the US FDA now permitting a 1-year deferral. Transparency, involvement of stakeholders, and careful evaluation of risk and societal benefit should be part of future policy discussions on this issue. PMID- 27389484 TI - Insights into blood cell formation from hemogenic endothelium in lesser-known anatomic sites. AB - BACKGROUND: Hematopoietic stem and progenitor cells (HSPCs) are generated de novo in the embryo in a process termed the endothelial to hematopoietic transition (EHT). EHT is most extensively studied in the yolk sac and dorsal aorta. Recently new sites of hematopoiesis have been described, including the heart, somites, head, and venous plexus of the yolk sac. RESULTS: We examined sites of HSPC formation in well-studied and in less well-known sites by mapping the expression of the key EHT factor Runx1 along with several other markers by means of confocal microscopy. We identified sites of HSPC formation in the head, heart and somites. We also identified sites of HSPC formation in both the arterial and venous plexuses of the yolk sac, and show that progenitors with lymphoid potential are enriched in hematopoietic clusters in close proximity to arteries. Furthermore, we demonstrate that many of the cells in hematopoietic clusters resemble monocytes or granulocytes based on nuclear shape. CONCLUSIONS: We identified sites of HSPC formation in the head, heart, and somites, confirming that embryonic hematopoiesis is less spatially restricted than previously thought. Furthermore, we show that HSPCs in the yolk sac with lymphoid potential are located in closer proximity to arteries than to veins. Developmental Dynamics 245:1011-1028, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27389487 TI - Protective effects of Urtica dioica L. on experimental testicular ischaemia reperfusion injury in rats. AB - In this study, it was aimed to examine the effects of Urtica dioica L. (UD) that has antioxidant feature in the experimental testicular I/R model in rats in terms of anti-apoptotic and antioxidative effects. In our study, 24 male rats were divided into three groups: control group, I/R group and I/R + UD (2 mg kg-1 ) group. Seminiferous tubule calibre measurement, Johnson score, haematoxylin-eosin staining, proliferative cell nucleus antigen (PCNA) immunohistochemical staining and TUNEL as histopathological have been conducted. The structural deterioration in the testicular on I/R group has reduced after the treatment of UD. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end labelling (TUNEL), and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of UD-treated rats in the I/R group. The I/R + UD group showed a decrease in malondialdehyde levels and an increase in the activities of superoxide dismutase, catalase and glutathione peroxidase in comparison with the I/R group. It could be concluded that protective effects of UD on the I/R testicles are via reduction of histological damage, apoptosis, oxidative stress and lipid peroxidation. PMID- 27389496 TI - Erratum: Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice. PMID- 27389497 TI - Mathematical 3D modelling and sensitivity analysis of multipolar radiofrequency ablation in the spine. AB - Radiofrequency ablation is a valuable tool in the treatment of many diseases, especially cancer. However, controlled heating up to apoptosis of the desired target tissue in complex situations, e.g. in the spine, is challenging and requires experienced interventionalists. For such challenging situations a mathematical model of radiofrequency ablation allows to understand, improve and optimise the outcome of the medical therapy. The main contribution of this work is the derivation of a tailored, yet expandable mathematical model, for the simulation, analysis, planning and control of radiofrequency ablation in complex situations. The dynamic model consists of partial differential equations that describe the potential and temperature distribution during intervention. To account for multipolar operation, time-dependent boundary conditions are introduced. Spatially distributed parameters, like tissue conductivity and blood perfusion, allow to describe the complex 3D environment representing diverse involved tissue types in the spine. To identify the key parameters affecting the prediction quality of the model, the influence of the parameters on the temperature distribution is investigated via a sensitivity analysis. Simulations underpin the quality of the derived model and the analysis approach. The proposed modelling and analysis schemes set the basis for intervention planning, state- and parameter estimation, and control. PMID- 27389499 TI - Unmixing hysteresis loops of the late Miocene-early Pleistocene loess-red clay sequence. AB - Magnetic paleoclimatic records often represent mixed environmental signals. Unmixing these signals may improve our understanding of the paleoenvironmental information contained within these records, but such a task is challenging. Here we report an example of numerical unmixing of magnetic hysteresis data obtained from Chinese loess and red clay sequences. We find that the mixed magnetic assemblages of the loess and red clay sediments both contain a component characterized by a narrow hysteresis loop, the abundance of which is positively correlated with magnetic susceptibility. This component has grain sizes close to the superparamagnetic/stable single domain boundary and is attributed to pedogenic activity. Furthermore, a wasp-waisted component is found in both the loess and red clay, however, the wasp-waisted form is more constricted in the red clay. We attribute this component to a mixture of detrital ferrimagnetic grains with pedogenic hematite. The abundance of this component decreases from the base to the top of the red clay, a pattern we attribute to decreased hematite production over the Chinese Loess Plateau (CLP) due to long-term climate cooling. This work demonstrates the potential of hysteresis loop unmixing to recover quantitative paleoclimatic information carried by both low and high coercivity magnetic minerals. PMID- 27389500 TI - Kinetic Analysis of Temperature-Programmed Autoxidation of Ethyl Eicosapentaenoate and Ethyl Docosahexaenoate. AB - On the basis of an autocatalytic and a first order reaction kinetics, a nonisothermal oxidation reaction model was developed for n-3 polyunsaturated fatty acid (PUFA) under temperature-programmed linear heating conditions. With this model, the activation energy of oxidative reaction can easily be obtained with at least three linear heating conditions. The temperature-programmed oxidation experiments of ethyl eicosapentaenoate and ethyl docosahexaenoate were done under linear heating conditions of 4 to 12 K/h. The activation energies and the frequency factors obtained were in good agreement with those by the isothermal oxidation experiments reported previously. PMID- 27389501 TI - Inhibition of DNA Topoisomerase I by Dihydrotanshinone I, Components of a Medicinal Herb Salvia miltiorrhiza Bunge. AB - Dihydrotanshinone I induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, but topoisomerase II-mediated DNA cleavage was not affected. In a DNA relaxation assay using calf thymus DNA topoisomerase I and supercoiled pBR322 plasmid DNA, dihydrotanshinone I reduced topoisomerase I mediated DNA relaxation in a dose-dependent manner. Heat treatment (65 degrees C) of the reaction mixture containing dihydrotanshinone I and topoisomerase I resulted in a substantial reduction in DNA cleavage, suggesting topoisomerase I and dihydrotanshinone I may form a reversible cleavable complex to induce DNA damage. A DNA unwinding assay using T4 DNA ligase showed that dihydrotanshinone I is a very weak DNA intercalator. These results suggest that dihydrotanshinone I inhibits the catalytic activity of topoisomerase I by the formation of a cleavable complex and at least in part through the intercalation into DNA. PMID- 27389502 TI - Chemo-enzymatic Synthesis of both Enantiomers of myo-Inositol 1,3,4,5 tetrakisphosphate. AB - D-Ins(1,3,4,5)P4 and unnatural L-Ins(1,3,4,5)P4 were prepared in gram-quantities from D- and L-2,6-di-O-benzyl-myo-inositol by a chemical phosphorylation and deprotection step in high yield and purity without extensive purification. The optically pure benzyl derivatives were obtained by enzyme-catalyzed resolution of racemic 2,6-di-O-benzyl-myo-inositol under acyl-transfer conditions in vinyl acetate as the acyl donor. The lipase of Candida antarctica only acetylated regio and enantio-selectively the L-enantiomer, providing exclusively L-5-acetyl-2,6 di-O-benzyl-myo-inositol, whereas the D-enantiomer remained unchanged. PMID- 27389503 TI - Production of Vitamin B6 in Rhizobium. AB - The production of vitamin B6 was studied in about 1,590 bacterial isolates from soil, and an isolate, 28-21, identified as Rhizobium leguminosarum was obtained as a vitamin B6 high producer. Then, the production of vitamin B6 by commercially available Rhizobium strains was examined, and many of the tested strains excreted large amounts of vitamin B6 into the culture broth. The best producer of vitamin B6 was R. meliloti IFO 14782, which produced 51 mg per liter. Media study for the vitamin B6 production was done with R. meliloti IFO 14782; the strain was able to excrete 84 mg of vitamin B6 per liter, 79 mg per liter of which was pyridoxol. PMID- 27389504 TI - Deterioration of Tolerance to Hydrophobic Organic Solvents in a Toluene-Tolerant Strain of Pseudomonas putida under the Conditions Lowering Aerobic Respiration. AB - The growth curve (increase in the number of viable cells) of a toluene-tolerant strain Pseudomonas putida Px51T was not reproducible in the presence of harmful organic solvents, such as p-xylene and toluene. The survival often fluctuated the during late exponential phase of growth. The repetitive growth was obtained by maintaining pO2 20-40% (v/v) in the culture flask. However, even under these aerobic conditions, the cells starved for a carbon source were killed by exposure to harmful solvents. The tolerance to organic solvents was lowered greatly by treatment with a proton conductor, carbonyl cyanide m-chlorophenylhydrazone (CCCP), or an electron transport chain inhibitor, sodium azide. Px51T treated with CCCP lost tolerance to a wide variety of organic solvents with log P ow of 2.6-4.2, which the organism usually tolerates. These results indicate that the solvent tolerance of Px51T depends upon on energy produced by aerobic respiration. PMID- 27389505 TI - cDNA Subtractive Cloning of Genes Expressed during Early Stage of Appressorium Formation by Magnaporthe grisea. AB - The conidial germ tube of the fungus Magnaporthe grisea differentiates an infection-specific structure, an appressorium, for penetration into the host plant. Formation of the appressorium is also observed on synthetic solid substrata such as polycarbonate. We found that a plant lectin, concanavalin A, specifically suppressed the appressorium formation without affecting the germling adhesion if it was applied within 2-3 hours after germination. Standing on the result, we constructed a cDNA library that represents the early stage of germ tube development and/or appressorium formation from the 2.5-hour-old germ tubes using a cDNA subtraction strategy by the combination of the biotin labeled driver method and adapter-primed PCR method. Out of 686 colonies of the library, 158 distinct clones' nucleotide sequences were partially analyzed. Some clones' expression patterns were detected by RT-PCR and from those results, our library seemed to well represent the objective developmental stage of M. grisea. PMID- 27389506 TI - Six Diacylated Anthocyanins from the Storage Roots of Purple Sweet Potato, Ipomoea batatas. AB - Eight acylated anthocyanins were isolated from the storage roots of the purple sweet potato, Ipomoea batatas cv Yamagawamurasaki, which is the source of the food colorant "purple sweet potato color." Of these, six pigments were identified as diacylated anthocyanins, cyanidin and peonidin 3-O-(6-O-(E)-caffeyl-2-O-(6-O acyl- beta-D-glucopyranosyl)-beta-D-glucopyranoside)-5-O-beta-D-gluco pyranosides, in which each acyl subsutituent was a p-hydroxybenzoyl, (E)-caffeyl or (E)-ferulyl residue, mainly by NMR analyses. PMID- 27389507 TI - Stereoselective Syntheses of (-)-Podorhizol Lignan and its Derivatives: erythro and threo Preferential Aldol Condensation of Potassium Enolate from gamma Butyrolactone with Alkoxybenzaldehyde. AB - (-)-Podorhizol (1) was stereoselectively synthesized by erythro preferential aldol condensation of 3,4,5-trimethoxy- benzaldehyde with potassium enolate from (+)-(R)-3- (3,4-methylenedioxybenzyl)-4-butanolide (2) (erythro:threo=85:15). Erythro selectivity was observed in the aldol condensation of many alkoxybenzaldehydes with potassium enolate from (+)-gamma-butyrolactone 2. However, benzaldehydes having methoxy groups at both the 2 and 6 positions gave threo selectivity in the aldol condensation with potassium enolate from (+)-gamma butyrolactone 2. PMID- 27389508 TI - Toxicity of Cadmium Particle Dust in Bacterial Cells. AB - When Thiobacillus intermedius 13-1, Escherichia coli JM109, and Agrobacterium radiobacter IFO12665b1 were cultured in LB liquid medium containing 0.03 g or 0.1 g of cadmium particle dust, growth was strongly inhibited. Expose of cells to cadmium particle resulted in an increase in pH and concentration of ammonium ions. No cadmium particle attachment to the outer wall of T. intermedius or cell wall disruption was observed by transmission electron microscopy. PMID- 27389509 TI - Fluorogenic Substrates for Cathepsin D. AB - Fluorogenic substrates for cathepsin D; A-Tyr-Phe(NO2)-Leu-Leu (A; Ala-Arg-Pro Lys-Pro-Leu-Leu-, Arg-Pro-Lys-Pro-Leu-Leu-, Pro-Lys-Pro-Leu-Leu-, Lys-Pro-Leu-Leu , Pro-Leu-Leu-) and B-Phe(NO2)-Tyr-Leu-Leu (B; Arg-Pro-Lys-Pro-Leu-Leu-, Pro-Lys Pro-Leu-Leu-, Lys-Pro-Leu-Leu-, Pro-Leu-Leu-) (Phe(NO2), p-nitrophenylalanine) were synthesized and digested by cathepsin D and pepsin. The fluorescence at 303 nm (excitation at 260 nm) was increased with the hydrolysis of the substrates. The minimum detectable cathepsin D concentrations for these substrates were 0.5-4 nM and pepsin concentrations were 0.1-0.8 nM except Pro-Leu-Leu-Tyr-Phe(NO2)-Leu Leu under the following conditions: substrate concentration, 20 MUM; measuring time, 3 min. The hydrolysis rate constants (kcat/Km) of B-Phe(NO2)-Tyr-Leu-Leu for cathepsin D were same or 2-3 times greater than A-Tyr-Phe(NO2)-Leu-Leu. On the other hand, those of B-Phe(NO2)-Tyr-Leu-Leu for pepsin were the same or 4-20 times greater than A-Tyr-Phe(NO2)-Leu-Leu. The hydrolysis rates of the substrates by both enzymes tend to increase with the increase of the peptide chain length. The best substrate for cathepsin D was Arg-Pro-Lys-Pro-Leu-Leu-Phe(NO2)-Tyr-Leu Leu and its kcat/Km was 1.3 MUM(-1) s(-1). PMID- 27389510 TI - Identification of the New Hydrocarbon (Z,Z)-1,6,9-Heptadecatriene as the Secretory Component of Caloglyphus polyphyllae (Astigmata: Acaridae). AB - A new heptadecatriene was isolated from the acarid mite, Caloglyphus polyphyllae, as the major characteristic component which could be used to identify the species chemo-taxonomically. Its structure was elucidated as 1,6,9-heptadecatriene by partial hydrogenation and a subsequent GC/MS analysis of the dimethyldisulfide derivative, together with evidence of the terminal vinyl group and Z configuration of double bonds that was provided by GC-FT/IR and NMR. The triene was identified as (Z,Z)-1,6,9-heptadecatriene by its synthesis and is revealed to be a new compound as a natural product. PMID- 27389511 TI - Viscometry of Curdlan, a Linear (1->3)-beta-D-Glucan, in DMSO or Alkaline Solutions. AB - A simple method to obtain the molecular weight of curdlan was found by viscometry in its alkaline or DMSO solution. DMSO was found to be the most appropriate solvent for measuring Mv of curdlan. Based on two Sakurada-Houvink equations, [eta]=KM(a), which have been obtained so far in alkaline solutions, two sets of parameters of the equation in the DMSO solution, that is, K=3.5*10(-4), a=0.65 and K=1.6*10(-4), a=0.74 were introduced, respectively. Both parameter sets seemed to serve practically to measure the molecular weight of curdlan. In addition, using the equation obtained with several NaOH concentrations, the previous speculation that curdlan conformation changes from a rigid rod to random coil with alkaline concentration was confirmed. PMID- 27389512 TI - Syntheses and Potato Tuber-inducing Activities of Unnatural Long-chain OPC-9:0 and OPC-10:0. AB - The unnatural long-chain OPCs, OPC-9:0 and OPC-10:0, were respectively synthesized from the ethyl esters of OPC-7:0 and OPC-8:0. C2-carbon elongation was achieved via alkylation of the enolate of tert-butyl acetate. The potato tuber-inducing activity of OPC-10:0, as well as OPC-8:0, -6:0 and -4:0, was similar to that of jasmonic acid. OPC-9:0 also exhibited weak tuber-inducing activity. PMID- 27389513 TI - Preparation of 4-(4'-Hydroxyanilino)-5-anilinophthalimide and 4,5-Bis-(4' hydroxyanilino)-phthalimide by Microbial Hydroxylation. AB - A microbial screening indicated that two fungal strains, Beauveria bassiana DSM 1344=ATCC 7159 and Cunninghamella elegans DSM 1908=ATCC 9245, as well as four bacterial strains belonging to the genus Streptomyces were able to hydroxylate 4,5-dianilinophthalimide (DAPH, CGP52411) to 4-(4'-hydroxyanilino)-5 anilinophthalimide. Cunninghamella elegans DSM 1908 turned out to be the most active biocatalyst and was also able to form the dihydroxy derivative, 4,5-bis(4' hydroxyanilino)phthalimide. The reaction for the monohydroxylated biotransformation product was carried out on a preparative scale, and the culture conditions for the formation of 4-(4'-hydroxy- anilino)-5-anilinophthalimide with this strain were op-timized. PMID- 27389514 TI - Determination of a Small Quantity of Cystine in the Presence of a Large Amount of Cysteine. AB - A procedure is described to precisely determine a very small amount of cystine in the presence of a large amount of cysteine. After completely modifying cysteine with N-ethylmaleimide, the remaining reagent was reacted with DL-homocysteine. Cystine was determined, after being reduced with dithiothreitol, by the reaction with ninhydrin carried out under acidic conditions. The procedure makes it possible to precisely determine the amount of cystine present with cysteine in a concentration ratio of 1:2,000. By employing this procedure, auto-oxidation of cysteine to cystine in a mixture for the L-cysteine alpha,beta-elimination reaction was investigated. PMID- 27389515 TI - Simultaneous Determination of Lipid Hydroperoxides by HPLC-Post Column Systems. AB - Two HPLC-post column systems, a conventional-size system and a semi-micro system, for the simultaneous determination of lipid hydroperoxides were developed. The hydroperoxides of free fatty acids, phosphatidylcholines, triacylglycerols and cholesterol esters were individually determined at the pmol level with good reproducibility by using gradient elution and post-column detection with diphenyl 1-pyrenylphosphine. PMID- 27389516 TI - Anthocyanins in The Dark Purple Anthers of Tulipa gesneriana: Identification of Two Novel Delphinidin 3-O-(6-O-(Acetyl-alpha-Rhamnopyranosyl)-beta Glucopyranosides). AB - Two novel anthocyanins, delphinidin 3-O-(6-O-(2-O-acetyl-alpha-rhamnopyranosyl) beta-glucopyranoside) and delphinidin 3-O-(6-O-(3-O-acetyl-alpha-rhamnopyranosyl) beta-glucopyranoside), were identified from the anthers of Tulipa gesneriana. These and delphinidin 3-O-(6-O-(alpha-rhamnopyranosyl)-beta-glucopyranoside) made up over 80% of the anthocyanin content in the dark purple anthers and could be responsible for the intense color of the anthers. PMID- 27389517 TI - Identification of Blue Pigment Formed in a D-Xylose-Glycine Reaction System. AB - D-Xylose (1 M), glycine (0.1 M), and sodium hydrogencarbonate (0.1 M) were dissolved in aqueous 60% ethanol at pH 8.1 and left at 26.5 degrees C for 2 days in a dark room under nitrogen displacement. Blue pigment was isolated and purified from the blue solution by anionic exchange and gel filtration chromatographies. Blue pigment which was designated Blue-M1 (blue Maillard reaction intermediate-1) was identified as 5-{[1,4-(dicarboxymethyl)-5-(2,3 dihydroxypropyl)-2-pyrrolo[3,2-b]pyrrolyl]methine}-1,4-(dicarboxymethyl)-2-(1,2,3 trihydroxypropyl)-pyrrolo[3,2-b]pyrroly-lium. Blue-M1 is supposed to be a dimer of yellow colored pyrrolopyrrole-2-carboxaldehyde compounds. Blue-M1 that reacts readily to yellow compounds has a polymerizing activity, suggesting it is an important Maillard reaction intermediate through the formation of melanoidins. PMID- 27389518 TI - Work function engineering of SnO single crystal microplates with thermal annealing. AB - We synthesized black SnO single-crystal microplates via a sonochemical process and engineered the work function of the SnO microplates using thermal treatments. The as-synthesized SnO microplates have a wide (001) plane, as is clearly evident from TEM images and diffraction patterns. Surface potential measurements on the SnO microplates show that the work function changes as the annealing temperature increases. The TEM and XAS results after thermal treatments imply that the micro sized SnO(001) single-crystals are stable up to about 400 degrees C in air, after which the surface starts to become locally oxidized. Consequently, the long range ordering and lattice parameter of the SnO(001) single crystals started to change to make polycrystalline SnO2 at about 600 degrees C. These results demonstrate the ability to tune the work function of the microplates and suggest an intriguing way to engineer the electrical properties of nanostructures. PMID- 27389520 TI - Acute kidney injury in patients using amikacin in an era of carbapenem-resistant bacteria. PMID- 27389519 TI - Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer. AB - BACKGROUND: Complete resection of locally advanced sigmoid colon cancer (LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemoradiotherapy (neoCRT) followed by surgery as treatment of selected patients with unresectable LASCC. METHODS: We studied the patients with unresectable LASCC who received neoCRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external-beam radiotherapy to 50 Gy and capecitabine-based chemotherapy every 3 weeks. Surgery was scheduled 6-8 weeks after radiotherapy. RESULTS: Twenty-one patients were included in this study. The median follow-up was 42 months (range, 17-57 months). All patients completed neoCRT and surgery. Resection with microscopically negative margins (R0 resection) was achieved in 20 patients (95.2%). Pathologic complete response was observed in 8 patients (38.1%). Multivisceral resection was necessary in only 7 patients (33.3%). Two patients (9.5%) experienced grade 2 postoperative complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0 (ypM0) disease, the cumulative probability of 3 year local recurrence-free survival, disease-free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3-year overall survival was 95.2% and bladder function was well preserved. CONCLUSION: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate. PMID- 27389521 TI - Associations between personality disorder characteristics and treatment outcomes in people with co-occurring alcohol misuse and depression. AB - BACKGROUND: Personality disorders are highly comorbid with alcohol misuse and depressive symptomatology; however, few studies have investigated treatment outcomes in this population. The aim of this study was to examine relationships between baseline personality disorder cluster profiles and overall and treatment related changes for those with co-occurring alcohol misuse and depression. METHODS: Secondary analysis was conducted using a subset of data (N = 290) from two randomised controlled trials of psychological interventions for co-occurring alcohol misuse and depression, which did not specifically target personality disorders. Baseline dimensional personality disorder cluster scores were derived from the International Personality Disorder Examination Questionnaire (IPDEQ). Four treatment conditions were compared: a brief integrated intervention, followed by no further treatment, or nine further sessions of integrated-, alcohol-, or depression-focused treatment. Associations between IPDEQ scores and changes in alcohol use, depressive symptoms and functioning from baseline to the 6- and the 12-month follow-ups were of primary interest. RESULTS: Personality disorder cluster scores moderately negatively impacted on overall change (primarily Cluster C), as well as treatment-related outcomes (primarily Cluster A), particularly changes in depressive symptoms and psychosocial functioning. Longer interventions appeared to be more effective in the longer-term (e.g., at 12-month follow-up), with integrated interventions relatively more effective than single-focused ones for individuals with higher personality disorder cluster scores. CONCLUSIONS: Greater attention needs to be paid to particular personality disorder clusters during the assessment and treatment of individuals with co occurring alcohol misuse and depression. Integrated interventions, incorporating motivational interviewing and cognitive behaviour therapy, may provide a useful therapeutic framework. Integrated interventions also provide opportunities for adjunctive components focussing on other issues and coping strategies (e.g., to offset negative affective states), potentially tailored to the characteristics and needs of individual participants. PMID- 27389522 TI - Sex differences in in-hospital mortality following a first acute myocardial infarction: symptomatology, delayed presentation, and hospital setting. AB - BACKGROUND: Women generally wait longer than men prior to seeking treatment for acute myocardial infarction (AMI). They are more likely to present with atypical symptoms, and are less likely to be admitted to coronary or intensive care units (CCU or ICU) compared to similarly-aged males. Women are more likely to die during hospital admission. Sex differences in the associations of delayed arrival, admitting ward, and mortality have not been thoroughly investigated. METHODS: Focusing on presenting symptoms and time of presentation since symptom onset, we evaluated sex differences in in-hospital mortality following a first AMI in 4859 men and women presenting to three emergency departments (ED) from December 2008 to February 2014. Sex-specific risk of mortality associated with admission to either CCU/ICU or medical wards was calculated after adjusting for age, socioeconomic status, triage-assigned urgency of presentation, blood pressure, heart rate, presenting symptoms, timing of presentation since symptom onset, and treatment in the ED. Sex-specific age-adjusted attributable risks were calculated. RESULTS: Compared to males, females waited longer before seeking treatment, presented more often with atypical symptoms, and were less likely to be admitted to CCU or ICU. Age-adjusted mortality in CCU/ICU or medical wards was higher among females (3.1 and 4.9 % respectively in CCU/ICU and medical wards in females compared to 2.6 and 3.2 % in males). However, after adjusting for variation in presenting symptoms, delayed arrival and other risk factors, risk of death was similar between males and females if they were admitted to CCU or ICU. This was in contrast to those admitted to medical wards. Females admitted to medical wards were 89 % more likely to die than their male counterparts. Arriving in the ED within 60 min of onset of symptoms was not associated with in-hospital mortality. Among males, 2.2 % of in-hospital mortality was attributed to being admitted to medical wards rather than CCU or ICU, while for females this age adjusted attributable risk was 4.1 %. CONCLUSIONS: Our study stresses the need to reappraise decision making in patient selection for admission to specialised care units, whilst raising awareness of possible sex-related bias in management of patients diagnosed with an AMI. PMID- 27389523 TI - Expanding the Phenotype of TRNT1-Related Immunodeficiency to Include Childhood Cataract and Inner Retinal Dysfunction. AB - IMPORTANCE: A multiorgan syndromic disorder characterized by sideroblastic anemia, immunodeficiency, periodic fever, and developmental delay with an uncharacterized retinal dystrophy is caused by TRNT1. This report of a family with a homozygous mutation in TRNT1 expands the ocular phenotype to include cataract and inner retinal dysfunction and details a mild systemic phenotype. OBSERVATIONS: A consanguineous family with 3 affected children was investigated. Key clinical features comprised hypogammaglobulinemia, short stature with microcephaly, cataract, and inner retinal dysfunction without sideroblastic anemia or developmental delay. Two siblings had poor balance and 1 sibling had sensorineural hearing loss. The oldest sibling had primary ovarian failure diagnosed at age 14.5 years. Exome sequencing identified a homozygous missense variant in TRNT1, c.295C>T (p.Arg99Trp) in all 3 patients. The sibling with hearing loss also harbored a homozygous mutation in GJB2, c.71G>A (p.Trp24*), which is an established cause of sensorineural hearing loss. CONCLUSIONS AND RELEVANCE: This family expands the ocular and systemic phenotypes associated with mutations in TRNT1, demonstrating phenotypic variability and highlighting the need for ophthalmic review of these patients. PMID- 27389524 TI - First report and histological features of Chlamydia pecorum encephalitis in calves in New Zealand. AB - CASE HISTORY: Between September and October 2013, 40 of 150 crossbred Friesian dairy calves on a farm in the Manawatu region of New Zealand developed neurological signs when between 1 and 3 months of age. Calves were grazed in multiple mobs and calves from each mob were affected. A variable response was observed to initial treatment with thiamine, fluoroquinolone antibiotics and non steroidal anti-inflammatory drugs. CLINICAL AND PATHOLOGICAL FINDINGS: Affected calves exhibited a range of neurological signs that included generalised depression, hind limb ataxia with a stiff gait, and knuckling of the fetlocks. In advanced cases, calves became recumbent with opisthotonous. Over a 4-week period, 13 calves died or were subject to euthanasia and a thorough necropsy was performed on three of these calves. Necropsy findings included fibrinous peritonitis, pleuritis and pericarditis, with no gross abnormalities visible in the brain or joints. Histology of the brain was possible in seven of the affected calves, with lesions ranging from lymphocytic and histiocytic vasculitis and meningoencephalitis, to extensive thrombosis and neutrophilic inflammation. Immunohistochemistry using an anti-chlamydial lipopolysaccharide antibody revealed positive immuno-staining in all seven cases, with no brain samples exhibiting immunostaining for Histophilus somni. DNA was extracted from a sample of fresh brain from one case and chlamydial DNA sequences were amplified by PCR and found to be identical to Chlamydia pecorum. PCR was also performed on formalin-fixed brain tissue from three of the other cases, but no chlamydial DNA was amplified. DIAGNOSIS: Chlamydia pecorum meningoencephalomyelitis (sporadic bovine encephalomyelitis). CLINICAL RELEVANCE: This is the first time that C. pecorum has been confirmed as a cause of clinical disease in New Zealand. Practitioners should be aware of this disease as a differential in calves with neurological signs, and submit samples of formalin-fixed brain as well as fresh brain to enable confirmation of suspected cases using PCR analysis. Furthermore, these cases illustrate that the histological lesions in the brains of calves with C. pecorum are more variable than previously reported, and pathologists should be aware that histological features may overlap with those traditionally ascribed to other organisms, such as H. somni. PMID- 27389525 TI - Biosynthesis of the High-Value Plant Secondary Product Benzyl Isothiocyanate via Functional Expression of Multiple Heterologous Enzymes in Escherichia coli. AB - Plants produce a wide variety of secondary metabolites that are highly nutraceutically and pharmaceutically important. Isothiocyanates, which are found abundantly in cruciferous vegetables, are believed to reduce the risk of several types of cancers and cardiovascular diseases. The challenges arising from the structural diversity and complex chemistry of these compounds have spurred great interest in producing them in large amounts in microbes. In this study, we aimed to synthesize benzyl isothiocyanate in Escherichia coli via gene mining, pathway engineering, and protein modification. Two chimeric cytochrome P450 enzymes were constructed and functionally expressed in E. coli. The E. coli cystathionine beta lyase was used to replace the plant-derived C-S lyase; its active form cannot be expressed in E. coli. Suitable desulfoglucosinolate:PAPS sulfotransferase from Arabidopsis thaliana ecotype Col-0 and myrosinase from Brevicoryne brassicae were successfully mined from the database. Biosynthesis of benzyl isothiocyanate by the combined expression of the optimized enzymes in vitro was confirmed by gas chromatography-mass spectrometry analysis. This study provided a proof of concept for the production of benzyl isothiocyanate by microbially produced enzymes and, importantly, laid the groundwork for further metabolic engineering of microbial cells for the production of isothiocyanates. PMID- 27389526 TI - The dilemma of diabetes in chronic inflammatory demyelinating polyneuropathy. AB - PURPOSE: We reviewed the literature on chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetes mellitus (DM) and explored real-world data on the prevalence and treatment of CIDP within DM. METHODS: A literature search of Scopus was performed for the terms chronic inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyneuropathy, CIDP, and prevalence, incidence, epidemiology, or diabetes; peripheral neuropathy and prevalence or diabetes. We also searched through the reference lists of the resulting publications for additional findings that may have been missed. Additional publications on guidelines for the diagnosis of CIDP and diabetic neuropathy were also included. A descriptive analysis of the 2009-2013 PharMetrics PlusTM Database was performed to estimate the prevalence and treatment of CIDP within the DM population. RESULTS: There is an increasing body of literature suggesting that the prevalence of CIDP tends to be higher in diabetic patients, especially in those of older age. Our real-world data seem to support published findings from the literature. For the total cohort (N=101,321,694), the percent prevalence of CIDP (n=8,173) was 0.008%; DM (n=4,026,740) was 4%. The percent prevalence of CIDP without DM (n=5,986) was 0.006%; CIDP with DM (n=2,187) was 9-fold higher at 0.054%. For patients >50years old, there was a significantly higher percentage of CIDP with DM than CIDP without DM. Approximately 50% of CIDP patients were treated with IVIg, 23%-24% with steroids, 1%-2% with PE, and 20%-23% received no treatment. CONCLUSIONS: In addition to the growing evidence of higher prevalence of CIDP in DM, our findings reinforce the need for heightened awareness of the association of CIDP and DM. PMID- 27389527 TI - Inhospitable Healthcare Spaces: Why Diversity Training on LGBTQIA Issues Is Not Enough. AB - In an effort to address healthcare disparities in lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations, many hospitals and clinics institute diversity training meant to increase providers' awareness of and sensitivity to this patient population. Despite these efforts, many healthcare spaces remain inhospitable to LGBTQ patients and their loved ones. Even in the absence of overt forms of discrimination, LGBTQ patients report feeling anxious, unwelcome, ashamed, and distrustful in healthcare encounters. We argue that these negative experiences are produced by a variety of subtle, ostensibly insignificant features of healthcare spaces and interpersonal interactions called microaggressions. Healthcare spaces and providers often convey heteronormative microaggressions, which communicate to LGBTQ-and, we suggest, intersex and asexual (IA)-people that their identities, experiences, and relationships are abnormal, pathological, unexpected, unwelcome, or shameful. We identify heteronormative microaggressions common to healthcare settings and specify how they negatively impact LGBTQIA patients. We argue that standard diversity training cannot sufficiently address heteronormative microaggressions. Despite these challenges, healthcare institutions and providers must take responsibility for heteronormative microaggressions and take steps to reduce their frequency and mitigate their effects on LGBTQIA care. We conclude by offering strategies for problem-solving at the level of medical education, institutional culture and policy, and individual awareness. PMID- 27389529 TI - Tips to improve the Discussion-section in a scientific paper. PMID- 27389528 TI - A survey of the perceptions and behaviors of chiropractic interns pertaining to evidence-based principles in clinical decision making. AB - OBJECTIVE: This study explored how chiropractic interns applied evidenced-based concepts, the sources of evidence they used, and how useful they perceived these sources to be in clinical decision making. METHODS: A questionnaire containing 13 items in a Likert 5-point scale was administered to 28 chiropractic interns to gather information on the evidence types they commonly accessed and their perceived usefulness of these sources in clinical decision making. The interns were in the 8th semester of the training program. RESULTS: There was a 93% (n = 26) response rate. Clinical guidelines were rated as the most helpful resource in clinical decision making (81%), followed by lecture materials (77%), journals (54%), databases (50%), and textbooks (35%). Students recognized scientific evidence as the most important aspect in clinical decision making. They found their personal experience and the views of their clinician to be equally important and patient preference the least. CONCLUSION: Interns routinely employed high-quality levels of evidence in clinical decision making. They also considered their early, limited clinical experience as important as that of their clinical supervisor in decision making. This finding should be investigated further. PMID- 27389530 TI - The outcome of endoscopic management of bile leakage after hepatobiliary surgery. AB - BACKGROUND/AIMS: Despite improvements in surgical techniques and postoperative patient care, bile leakage can occur after hepatobiliary surgery and may lead to serious complications. The aim of this retrospective study was to evaluate the efficacy of endoscopic treatment of bile leakage after hepatobiliary surgery. METHODS: The medical records of 20 patients who underwent endoscopic retrograde cholangiopancreatography because of bile leakage after hepatobiliary surgery from August 2009 to September 2014 were reviewed retrospectively. Endoscopic treatment included insertion of an endoscopic retrograde biliary drainage stent after endoscopic sphincterotomy. RESULTS: Most cases of bile leakage presented as percutaneous bile drainage through a Jackson-Pratt bag (75%), followed by abdominal pain (20%). The sites of bile leaks were the cystic duct stump in 10 patients, intrahepatic ducts in five, liver beds in three, common hepatic duct in one, and common bile duct in one. Of the three cases of bile leakage combined with bile duct stricture, one patient had severe bile duct obstruction, and the others had mild strictures. Five cases of bile leakage also exhibited common bile duct stones. Concerning endoscopic modalities, endoscopic therapy for bile leakage was successful in 19 patients (95%). One patient experienced endoscopic failure because of an operation-induced bile duct deformity. One patient developed guidewire-induced microperforation during cannulation, which recovered with conservative treatment. One patient developed recurrent bile leakage, which required additional biliary stenting with sphincterotomy. CONCLUSIONS: The endoscopic approach should be considered a first-line modality for the diagnosis and treatment of bile leakage after hepatobiliary surgery. PMID- 27389531 TI - The role of B cells and autoantibodies in neuropsychiatric lupus. AB - The central nervous system manifestations of SLE (neuropsychiatric lupus, NPSLE) occur frequently, though are often difficult to diagnose and treat. Symptoms of NPSLE can be quite diverse, including chronic cognitive and emotional manifestations, as well as acute presentations, such as stroke and seizures. Although the pathogenesis of NPSLE has yet to be well characterized, B-cell mediated damage is believed to be an important contributor. B-cells and autoantibodies may traverse the blood brain barrier promoting an inflammatory environment consisting of glia activation, neurodegeneration, and consequent averse behavioral outcomes. This review will evaluate the various suggested roles of B-cells and autoantibodies in NPSLE, as well as therapeutic modalities targeting these pathogenic mediators. PMID- 27389532 TI - Global longitudinal strain as a biomarker in diabetic cardiomyopathy. A comparative study with Gal-3 in patients with preserved ejection fraction. AB - OBJECTIVES: To establish a relationship between global longitudinal strain (GLS) and Galectin-3 in pre-clinical heart failure in diabetic patients. Galectin-3 is a biomarker in heart failure with depressed ejection fraction (HFdEF). The hypothesis is presented that Galectin-3 is related to GLS and can detect left ventricular dysfunction in heart failure with preserved ejection fraction. METHODS: Galectin-3 and GLS were measured in 121 asymptomatic individuals: 14 diabetics with mild depressed ejection fraction (mdEF) (LVEF 47.0+/-6.9); 76 diabetics with preserved ejection fraction (LVEF 61+/-5.5), and 31 controls (61.7+/-5.1). RESULTS: Galectin-3 was elevated in all diabetics vs controls (3.46+/-1.36 ng/ml vs 2.78+/-0.91 ng/ml; p=.003). It was also elevated in mdEF (3.76+/-1.12 ng/ml vs 2.78+/-0.9 ng/ml; p=.009) and pEF subjects (3.41+/-1.40 ng/ml vs 2.78+/-0.9 ng/ml; p=.058), respectively, vs controls. No difference in Gal-3 was found between diabetic groups (p=.603). Diabetics had lower GLS than controls (-18.5+/-3.9 vs -20+/-2.6; p=.022). Diabetics with mdEF had lower GLS than those with pEF (-13.3+/-3.41 vs -19+/-3.2; P<.001). There was no difference in GLS with pEF compared to controls (-19.4+/-3.2 vs -20+/-2.6; p=.70). CONCLUSIONS: Galectin-3 is elevated in diabetic patients with mdEF, and is associated with a diminished GLS. GLS could be an early marker of left ventricular dysfunction as well as evidence of diabetic cardiomyopathy. PMID- 27389534 TI - P/CAF-mediated spermidine acetylation regulates histone acetyltransferase activity. AB - Histones and polyamines are important determinants of the chromatin structure. Histones form the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional regulation. Polyamines, including spermidine, are also targets of both cytoplasmic and nuclear acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report the interplay between polyamines metabolism and levels of histone acetylation, but the molecular basis of this effect is still unclear. In this work, we have analyzed the in vitro effect of spermidine on histone H3 acetylation catalyzed by P/CAF, a highly conserved histone acetyltransferase (HAT) (E.C. 2.3.1.48). We have observed that spermidine at very low concentrations activates P/CAF, while it has an inhibitory effect at concentrations higher than 4 MUM. In addition, the in vitro bimodal effect of spermidine on histone H3 acetylation was also distinctly observed in vivo on polytene chromosomes of Drosophila melanogaster. We also performed kinetic studies indicating that the activating effect of low spermidine concentrations on P/CAF-HAT activity is based on its involvement as a substrate for P/CAF to produce N8-acetylspermidine that is able in turn to increase the enzyme activity up to four fold. PMID- 27389533 TI - [Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population]. AB - OBJETIVE: The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. METHODS: In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. RESULTS: The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects without CAC, while those with CAC 1-99, 100-399, and >400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01 2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. CONCLUSION: Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population. PMID- 27389537 TI - Fessas P, Stamatoyannopoulos G. Hereditary persistence of fetal hemoglobin in Greece: a study and a comparison. Blood. 1964;24(3):223-240. PMID- 27389536 TI - Blood's 70th anniversary: CARs on the Blood highway. PMID- 27389535 TI - The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis. AB - Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB) in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating "stress" signals of 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a "drugable" therapeutic target in cancer. PMID- 27389538 TI - Gene therapy for PID: the end of the beginning? PMID- 27389539 TI - Just 1 test to diagnose AML?!! PMID- 27389540 TI - A new junctional hierarchy. PMID- 27389541 TI - Predicting relevant immunogenetic disparities. PMID- 27389542 TI - IL-2, the next best thing in chronic GVHD therapy? PMID- 27389543 TI - A radiologist's guide to the clinical scales used in the 2015 Endovascular Stroke Trials and the Revised American Heart Association/American Stroke Association Guidelines for Endovascular Stroke Treatment. AB - In 2015, five trials demonstrated the efficacy of endovascular treatment for acute stroke, culminating in the revised American Heart Association/American Stroke Association (AHA/ASA) recommendations for stroke management. The different clinical scales used in these trials may be unfamiliar to emergency and on-call radiologists. The modified Rankin Scale was used to describe patient disability for prestroke assessment in three of the trials and for the 90-day follow up in all five trials. The Barthel index was used in one trial to score prestroke ability to perform activities of daily living. The NIH Stroke Scale was used as part of eligibility criteria in four of the stroke trials to assess pre-existing neurological deficits. Also, the modified Rankin Scale and the NIH Stroke Scale are used in the revised AHA/ASA recommendations. By understanding these scales, emergency and on-call radiologists will better appreciate the stroke patient's condition and will be able to more actively collaborate in the care of acute stroke patients. PMID- 27389544 TI - LncRNA UCA1-miR-507-FOXM1 axis is involved in cell proliferation, invasion and G0/G1 cell cycle arrest in melanoma. AB - Recently, the incidence of melanoma has been on the rise. Patients with distant metastasis share poor prognosis. Increasing studies have been conducted to clarify the molecular mechanisms as well as to investigate potential effective therapeutic targets in the development of melanoma. This study focuses on the LncRNA UCA1 and its downstream regulated factors. In our experiments, UCA1 expression was discovered to be upregulated in melanoma tissues and cells, while the depletion of UCA1 led to the inhibition of cell proliferation, invasion and cell cycle arrest. To further our understanding of the mechanisms of UCA1, a system of experiments was built. We found that miR-507 could directly bind to UCA1 at the miRNA recognition site, and that there was a negative correlation between miR-507 and UCA1. Additionally, FOXM1 is a target of miR-507 and can be downregulated by either miR-507 overexpression or UCA1 depletion. Downregulated FOXM1 was analogous to the depletion of UCA1 and the overexpression of miR-507. These results, taken together, provide evidence for a novel UCA1 interaction regulatory network in tumorigenesis of melanoma. PMID- 27389545 TI - Fifteen-minute consultation: the agar plates your microbiology colleagues want you to be scared about. AB - The WHO has recognised antibiotic resistance as one of the greatest threats to human health. As a microbiologist, antibiotic resistance is a problem that keeps me awake at night and inevitably the impact of antibiotic resistance on paediatricians is a matter of when, and not if. I fear for the future of paediatric services such as neonatology, oncology and elective surgery. A recent US study found that 26.8% of post chemotherapy infections and 38.7-50.9% of post operative infections were caused by bacteria resistant to standard antibiotic prophylaxis. The authors predicted that this will lead to an additional 6300 infection-related deaths in the USA each year. Closer to home, David Cameron commissioned a review into antimicrobial resistance in 2014 and the findings were extremely worrying. The report predicted that by 2050, 10 million annual worldwide deaths will be attributable to antimicrobial resistance. More than annual predicted cancer-associated and diabetes-associated mortality combined. The golden antibiotic era is certainly over. Selecting the most appropriate antibiotic to treat an infection depends on many factors, including route of administration, penetration to site of infection and pathogen susceptibility. Most clinicians do not need an in-depth understanding of bacterial resistance mechanisms as local microbiologists can provide expertise and advice. However, in an era of increasing antibiotic resistance, an insight into the organism factors that affect antibiotic selection can prove useful. PMID- 27389546 TI - What do I need to know about glycopeptide antibiotics? AB - Glycopeptides have been crucial in the fight against Gram-positive pathogens with their use within paediatrics becoming ever prevalent. This article reviews the pharmacology of the commonly used glycopeptides, vancomycin and teicoplanin, and discusses the practical aspects of their use in the clinical setting. PMID- 27389547 TI - Febrile neutropenia and refeeding syndrome. AB - We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues. PMID- 27389548 TI - Exposure to ambient bioaerosols is associated with allergic skin diseases in Greater Taipei residents. AB - Allergic skin diseases may result from various types of chemical and biological allergens. This study investigated the association between ambient bioaerosol exposure and allergic skin diseases by using the exposure data obtained from land use regression models and interpolated data. Data on daily average outpatient visits for atopic dermatitis (ICD-9-CM 691.8) and contact dermatitis and other eczema (ICD-9-CM 692.9) between November 2011 and August 2012 were obtained from the National Health Insurance Research Database. A generalized estimating equation was used to analyze the associations between the skin diseases and ambient bioaerosol levels. The results indicated that during the study period, contact dermatitis and other eczema were more prevalent than atopic dermatitis in the study area. Most cases were observed in districts of Taipei City and 3 major districts of New Taipei City, namely Xinzhuang, Banqiao, and Xindian. In univariate analysis, most bioaerosols were positively associated with both skin diseases. After adjustment for air pollution and sociodemographic factors, exposure to total fungal spores was significantly associated with atopic dermatitis in males (relative risk [RR] = 1.12; 95% confidence interval [CI] = 1.05-1.19). Contact dermatitis and other eczema had significant relationships with Cladosporium in males (RR = 1.07; 95% CI = 1.02-1.14) and with Aspergillus/Penicillium in females (RR = 1.04; 95% CI = 1.02-1.07). Meteorological parameters, namely wind speed, temperature, and rainfall, were also significantly associated with skin diseases. Our findings reveal that exposure to ambient bioaerosols is a significant and independent risk factor for allergic skin diseases. PMID- 27389549 TI - Levels, sources and risk assessment of PAHs in multi-phases from urbanized river network system in Shanghai. AB - Spatial-temporal distributions, sources identification and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in overlying water and surface sediments in urban river networks of Shanghai were studied. Analytical results showed that there was a significant seasonal variation in concentrations of ?16PAHs in water, suspended particulate matter (SPM) and sediment phases in this study area. The PAHs pollution in these multi-phases were in the medium level compared with other areas around the world, and the levels of PAHs contamination in SPM and sediment phases in hierarchical rivers showed TS (the third-order stream) > FS (the first order stream) > SS (the second-order stream). Two manners of isomer ratios and principal component analysis (PCA) were used to identify PAHs origins, and suggested that combustion processes are dominant for PAHs sources. The ratios of PAHs origins by fossil fuels combustion, coke burning and crude oil in hierarchical rivers were determined with FS > SS > TS in SPM and sediment phases, and the ratio of PAHs origins by traffic emissions was analyzed with TS > SS > FS. PAHs in water samples have a certain impact on aqueous ecological system especially due to the fact that the ?ceq values of nine PAHs were calculated from 0.715 to 15.831 MUg/L in winter, which inferred serious ecological risk to some special aquatic organisms. The calculations of MERMQ in sediment samples showed that the MERMQ values ranged from 0.021 to 1.209 in winter and 0.019 to 0.643 in summer, which suggested high toxicity at six sampling sites in winter and only one location in summer due to high levels of PAHs. Furthermore, the toxicity degree of sediments were demonstrated with TS > FS > SS. PMID- 27389551 TI - A field-based method to derive macroinvertebrate benchmark for specific conductivity adapted for small data sets and demonstrated in the Hun-Tai River Basin, Northeast China. AB - Ionic mixtures, measured as specific conductivity, have been increasingly concerned because of their toxicities to aquatic organisms. However, identifying protective values of specific conductivity for aquatic organisms is challenging given that laboratory test systems cannot examine more salt-intolerant species nor effects occurring in streams. Large data sets used for deriving field-based benchmarks are rarely available. In this study, a field-based method for small data sets was used to derive specific conductivity benchmark, which is expected to prevent the extirpation of 95% of local taxa from circum-neutral to alkaline waters dominated by a mixture of SO4(2-) and HCO3(-) anions and other dissolved ions. To compensate for the smaller sample size, species level analyses were combined with genus level analyses. The benchmark is based on extirpation concentration (XC95) values of specific conductivity for 60 macroinvertebrate genera estimated from 296 sampling sites in the Hun-Tai River Basin. We derived the specific conductivity benchmark by using a 2-point interpolation method, which yielded the benchmark of 249 MUS/cm. Our study tailored the method that was developed by USEPA to derive aquatic life benchmark for specific conductivity for basin scale application, and may provide useful information for water pollution control and management. PMID- 27389550 TI - Current levels and trends of selected EU Water Framework Directive priority substances in freshwater fish from the German environmental specimen bank. AB - Under the German environmental specimen bank programme bream (Abramis brama) were sampled in six German rivers and analysed for the priority hazardous substances dicofol, hexabromocyclododecane (HBCDD), hexachlorobenzene (HCB), hexachlorobutadiene (HCBD), heptachlor + heptachlor epoxide (HC + HCE), polybrominated diphenylethers (PBDEs), polychlorinated dibenzo-p-dioxins and furans and dioxin-like polychlorinated biphenyls (PCDD/Fs + dl-PCBs), and perfluorooctane sulfonic acid (PFOS). The aim was to assess compliance with the EU Water Framework Directive environmental quality standards for biota (EQSBiota) for the year 2013, and to analyse temporal trends for those substances that are of special concern. General compliance was observed for dicofol, HBCDD and HCBD whereas PBDEs exceeded the EQSBiota at all sites. For all other substances compliance in 2013 varied between locations. No assessment was possible for HC + HCE at some sites where the analytical sensitivity was not sufficient to cover the EQSBiota. Trend analysis showed decreasing linear trends for HCB and PFOS at most sampling sites between 1995 and 2014 indicating that the emission reduction measures are effective. Mostly decreasing trends or constant levels were also observed for PCDD/Fs and dl-PCBs. In contrast, increasing trends were detected for PBDEs and HBCDD which were especially pronounced at one Saar site located downstream of the industries and conurbation of Saarbrucken and Volklingen. This finding points to new sources of emissions which should be followed in the coming years. PMID- 27389552 TI - Covalent triazine-based framework: A promising adsorbent for removal of perfluoroalkyl acids from aqueous solution. AB - Perfluoroalkyl acids (PFAAs) are highly stable, persistent, and ubiquitous in the environment with significant concerns growing with regards to both human and ecosystem health. Due to the high stability to both biological and chemical attack, the only currently feasible approach for their removal from water is adsorbent technology. The main objective of this study was to assess a covalent triazine-based framework (CTF) adsorbent for removal from aqueous solutions of perfluoro C4, C6, and C8 carboxylates and sulfonates including the two C8s most commonly monitored, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Adsorption affinity and capacity were quantified and compared to three commonly used sorbents: pulverized microporous activated carbon, single-walled carbon nanotubes, and Amberlite IRA-400 anion-exchange resin. CTF adsorbent exhibited pronouncedly higher adsorption affinity and capacity of PFAAs than other test sorbents. The remarkably strong adsorption to CTF can be attributed to the favored electrostatic interaction between the protonated triazine groups on the inner wall of the hydrophobic CTF pore and the negatively charged head groups of the PFAAs intercalated between the CTF layers. The homogeneous, nanosized pores (1.2 nm) of CTF hindered adsorption of a large-sized dissolved humic acid, thus minimizing the suppression of PFAA adsorption. Additionally, regeneration of CTF was easily accomplished by simply raising pH > 11, which inhibited the electrostatic adsorptive interaction of PFAAs. PMID- 27389553 TI - Follistatin Expression in Human Invasive Breast Tumors: Pathologic and Clinical Associations. AB - Follistatin is a potent native activin antagonist that is expressed in the normal mammary gland and in different breast proliferative diseases. Despite experimental evidence that follistatin can modulate the breast cancer cell cycle, the clinical significance of follistatin expression in these tumors is unknown. The aim of this study was to correlate the intensity of follistatin expression in invasive breast cancer with some of its clinical and pathologic features, such as the disease stage and the hormonal receptor status. Paraffin blocks of tumor samples that had been fixed in buffered formalin were obtained from 154 women subjected to surgery for breast cancer between 2008 and 2012. Sections from all paraffin blocks were cut and processed together by immunohistochemistry using a commercial monoclonal antibody to human follistatin. The intensity of follistatin staining was unrelated to the menopausal status, the disease stage, the grade, progesterone receptor expression, and local or systemic recurrence. However, follistatin immunoreactivity was significantly stronger in estrogen receptor (ER) negative tumors than in ER-positive tumors. These findings suggest that follistatin expression in invasive breast cancer is unrelated to the disease severity and the risk of recurrence, but is more intense in ER-negative tumors. PMID- 27389555 TI - Comparison of Antibodies for Immunohistochemistry-based Detection of HER3 in Breast Cancer. AB - BACKGROUND: Growth factor receptor HER3 (ErbB3) lacks standardized immunohistochemistry (IHC)-based methods for formalin-fixed paraffin-embedded (FFPE) tissue samples. We compared 4 different anti-HER3 antibodies to explain the differences found in the staining results reported in the literature. MATERIALS AND METHODS: Four commercial HER3 antibodies were tested on FFPE samples including mouse monoclonal antibody clones, DAK-H3-IC and RTJ1, rabbit monoclonal antibody clone SP71, and rabbit polyclonal antibody (SAB4500793). Membranous and cytoplasmic staining patterns were analyzed and scored as 0, 1+, or 2+ according to the intensity of the staining and completeness of membranous and cytoplasmic staining. A large collection of HER2-amplified breast cancers (n=177) was stained with the best performing HER3 antibody. The breast cancer cell line, MDA-453, and human prostate tissue were used as positive controls. IHC results were confirmed by analysis of flow cytometry performed on breast cancer cell lines. Staining results of FFPE samples were compared with samples fixed with an epitope-sensitive fixative (PAXgene). RESULTS: Clear circumferential cell membrane staining was found only with the HER3 antibody clone DAK-H3-IC. Other antibodies (RTJ1, SP71, and polyclonal) yielded uncertain and nonreproducible staining results. In addition to cell membrane staining, DAK-H3-IC was also localized to the cytoplasm, but no nuclear staining was observed. In HER2 amplified breast cancers, 80% of samples were classified as 1+ or 2+ according to the HER3 staining on the cell membrane. The results from FFPE cell line samples were comparable to those obtained from unfixed cells in flow cytometry. IHC conducted on FFPE samples and on PAXgene-fixed samples showed equivalent results. CONCLUSIONS: We conclude that IHC with the monoclonal antibody, DAK-H3-IC, on FFPE samples is a reliable staining method for use in translational research. Assessment of membranous HER3 expression may be clinically relevant in selecting patients who may most benefit from pertuzumab or other novel anti-HER3 therapies. PMID- 27389554 TI - Nuclear Survivin as a Prognostic Factor in Squamous-Cell Carcinoma of the Oral Cavity. AB - Oral squamous-cell carcinoma (OSCC) and most human tumors are characterized by an imbalance of regulatory mechanisms controlling cell processes such as apoptosis. Survivin, a member of the inhibitor of apoptosis family, is overexpressed in most solid and hematological malignancies and correlates with a reduced overall survival rate. Thus, the aim of this study was to find a correlation between nuclear Survivin expression and clinicopathologic data and the prognosis in OSCC patients. A total of 152 OSCC samples were investigated by immunohistochemistry for nuclear Survivin expression. Then, Survivin was scored semiquantitatively using an immunoreactivity score (IRS), calculated by multiplying the percentage of positive cells with the staining intensity. Using a digital image analysis software, OSCC patients were stratified into 4 groups. Results showed that patients with a lower IRS score displayed better survival rates than patients with a higher IRS score, reaching statistical significance. As the expression of Survivin at the nuclear level seems to suggest a poor prognosis in OSCC patients, the evaluation of nuclear Survivin IRS may be a useful tool to identify patients with more aggressive and disseminated disease, influencing follow-up and therapeutic protocols. PMID- 27389556 TI - CDK8 Expression in Extrauterine Leiomyosarcoma Correlates With Tumor Stage and Progression. AB - Mediator is a multiprotein complex that acts as a versatile transcription coactivator in eukaryotes. CDK8 kinase complex is a 4-protein subunit of the mediator complex that can act as a transcriptional repressor or coactivator, depending on the specific pathways involved. Although the role of MED12 exon 2 mutations is documented in the pathogenesis of uterine leiomyomas, its role in extrauterine smooth muscle tumorigenesis is less clear. Similarly, there is a paucity of data on the role of CDK8 in extrauterine smooth muscle tumorigenesis and progression. Our study correlates immunohistochemical expression of CDK8 and MED12 with clinical and pathologic parameters in extrauterine leiomyosarcomas. Immunohistochemical expression of CDK8 and MED12 in leiomyosarcomas was correlated with the tumor grade, stage, and the presence of local recurrence or metastasis. MED12 was expressed in the majority of leiomyosarcomas regardless of their stage or grade. CDK8 expression was lost in 1 of 6 pT1 tumors, compared with 9 of 10 pT2 tumors (P=0.0076). When the second group was expanded to include those tumors that did not have a recorded pathologic stage but had local recurrence and distant metastases, the difference in CDK8 expression was also statistically significant. Loss of CDK8 expression by immunohistochemistry is more prevalent in somatic leiomyosarcomas presenting at a higher histopathologic stage, as well as with local and distant recurrence, and can be used to enhance the current predictive parameters. PMID- 27389557 TI - Ki67 Scoring in Pancreatic Neuroendocrine Tumors By a New Method. AB - Ki67 scoring is required for the grading of pancreatic neuroendocrine tumors. Ongoing debate exists about the best scoring method in terms of accuracy and practicality. Manual counting of cells in camera-captured/printed images is a widely used and accepted method and considered the most reliable one among the manual methods. It requires counting 500 to 2000 cells to determine the Ki67 score accurately and it is time and energy consuming. We investigated the possibility of achieving the same results by counting only a particular fraction of tumor cells in a printed image in a series of 45 (24 grade 1 and 21 grade 2) pancreatic neuroendocrine tumors. After counting Ki67-positive tumor cells in the whole image, the tumor cells were counted within one-tenth of the same image with the aid of a previously prepared grid on an acetate sheet. The cell number obtained was multiplied by 10 to estimate the total cell count and the Ki67 score was calculated. The agreement between the results of the acetate grid and conventional whole-image counting method was assessed. Near-perfect agreement was achieved regarding the total cell count and Ki67 score. The agreement on tumor grade between the two methods was perfect. The time spent on the process was significantly less than that spent on the conventional method. Although it needs to be validated in a larger series, the acetate grid method might be considered an alternative method for Ki67 scoring in neuroendocrine tumors. PMID- 27389558 TI - Characteristic Distribution Pattern of CD30-positive Cytotoxic T Cells Aids Diagnosis of Kikuchi-Fujimoto Disease. AB - INTRODUCTION: Histiocytic necrotizing lymphadenitis (or Kikuchi-Fujimoto disease) frequently occurs in Asian young adult females and typically presents as cervical lymphadenopathy with unknown etiology. Although large immunoblasts frequently appear in Kikuchi-Fujimoto disease, the diffuse infiltration of these cells can cause difficulty in establishing a differential diagnosis from lymphoma. In such cases, CD30 immunostaining may be used; however, the extent or distribution pattern of CD30-positive cells in Kikuchi-Fujimoto disease remains largely unknown. Here we investigated the expression of CD30 and its clinicopathologic significance. MATERIALS AND METHODS: We investigated 30 Kikuchi-Fujimoto disease and 16 control [6, systemic lupus erythematosus (SLE); 10, reactive lymphoid hyperplasia (RLH)] cases. RESULTS: The number of CD30-positive cells in Kikuchi Fujimoto disease was significantly more than that in SLE and RLH, and majority of these cells were located around necrotic areas. Moreover, double immunohistochemical staining showed these CD30-positive cells to be CD8-positive cytotoxic T cells, suggesting that activated cytotoxic T cells around necrotic areas are a characteristic feature of this disease. Clinicopathologic analysis showed that cases with abundant CD30-positive cells were predominantly female with only mild symptoms and normal laboratory data. CONCLUSIONS: In Kikuchi Fujimoto disease cases, CD30-positive cytotoxic T cells were abundant around necrotic areas; this histologic feature may be helpful to differentiate this disease from SLE and RLH. PMID- 27389559 TI - Expression of CDX2 and Thyroid Transcription Factor-1 in Oropharyngeal Undifferentiated Carcinomas: A Potential Diagnostic Pitfall. AB - Oropharyngeal undifferentiated carcinomas are rare and most are human papillomavirus related. Morphologically, they overlap with undifferentiated carcinomas from other organ sites, including the nasopharynx, lung, and gastrointestinal tract. Most have lymph node metastases at presentation and, especially when initially encountered in a lymph node, immunostains may be performed to determine the most likely primary site. We recently reviewed a case in consultation that strongly and diffusely expressed both thyroid transcription factor-1 (TTF-1, SPT24 clone) and CDX2, 2 widely used markers that are considered relatively lineage specific for lung/thyroid and intestinal differentiation, respectively. Unexpected expression of these markers could be misleading. However, they have not been previously assessed in oropharyngeal undifferentiated carcinoma. Here, we performed immunohistochemistry for CDX2 and TTF-1 (8G7G3/1 clone) on primary tumors and/or lymph node metastases from 11 in-house patients with previously characterized undifferentiated carcinoma of the oropharynx from 1992 to 2008. All were male with an average age of 56.7 years, and 5 (46%) initially presented with a neck mass. All were Epstein-Barr virus negative and 9 (82%) were human papillomavirus and p16 positive. CDX2 was positive in 6 of the 11 (55%) cases. However, staining was generally weak to moderate and/or nondiffuse. TTF-1 was negative in all the in-house cases and showed only rare, weakly positive cells in the consult case when TTF-1 was repeated using the 8G7G3/1 clone. Thus, CDX2 immunoreactivity is common, whereas TTF-1 expression is rare in oropharyngeal undifferentiated carcinomas. As a result, one should not rely on CDX2 as evidence of intestinal differentiation or origin in metastatic undifferentiated carcinomas in the neck, particularly when staining is not strong and diffuse. In addition, TTF-1 should be interpreted with caution especially when using the SPT24 clone. PMID- 27389560 TI - Molecular Analysis of Tumor Cell Components in Pilocytic Astrocytomas, Gangliogliomas, and Oligodendrogliomas. AB - Gliomas and glioneuronal tumors are histologically polymorphous tumors. They can harbor a clear cell "oligodendroglial-like" component that can be difficult to distinguish from tumor cells of oligodendrogliomas or neurons, particularly on small samples. Thus, knowledge of the pattern of molecular markers in different tumor cell components is essential to ensure reliable diagnosis. Here, we screened 14 pilocytic astrocytomas (PA), 12 gangliogliomas, and 13 oligodendrogliomas for the KIAA1549-BRAF fusion gene, IDH1/2 mutations, and 1p19q losses in various areas of interest representative of the different tumor cell components. Molecular patterns were analyzed according to histologic type, tumor cell components, and clinical data. The KIAA1549-BRAF fusion gene was detected only in 8 out of 11 PAs (73%) and in 3 out of 9 gangliogliomas (33%) (P=0.003). Interestingly, all of the studied areas of interest within the same tumor exhibited the same KIAA1549-BRAF fusion gene status. IDH1-R132H and 1p19q loss were found only in 12 out of the 13 oligodendrogliomas (P<0.0001). Our study shows that cellular polymorphism in PAs and gangliogliomas does not affect the results of molecular analysis investigating the status of the KIAA1549-BRAF fusion gene. Thus, this molecular analysis can be reliably used even if the sample size is limited and the selection of different tumor areas is not possible. PMID- 27389561 TI - Prenatal screening, diagnosis, and termination of pregnancy in First Nations and rural women. AB - OBJECTIVES: The objectives of the study were to assess differences in utilization of maternal serum screening (MSS) and prenatal diagnostic testing between population subgroups and to determine the impact on chromosomal anomaly birth rates. METHODS: This population-based cohort study included all female residents from Saskatchewan, Canada, who delivered a baby, experienced a fetal loss, or had a pregnancy termination between 2000 and 2005. In total, 93 171 women were included in the study dataset, with a subset (n = 35 527) evaluated to identify predictors of screening and diagnostic testing. Incidence and live birth prevalence of Down syndrome were compared across populations. RESULTS: MSS uptake was lower in First Nations (FN) women (9.6% vs 28.4%), and living in a rural health region moderated the difference (p < 0.001). Consequently, fewer chromosomal anomalies were prenatally diagnosed in FN women than in the rest of the population (8.3% vs 27%). Terminations of pregnancy for fetal anomaly occurred at a lower frequency amongst FN women (0.64 vs 1.34, per 1000 pregnancies), resulting in a smaller effect on Down syndrome birth rates. CONCLUSION: Utilization of MSS and diagnostic testing was lower in FN and rural populations. Further research will be necessary to understand the relevance of value preferences and access barriers. (c) 2016 John Wiley & Sons, Ltd. PMID- 27389562 TI - The State of the Journal of Insect Science. PMID- 27389563 TI - A New Genus of Macropsinae (Hemiptera: Cicadellidae) From Madagascar. AB - Paragalboa acuta GEN & SP N: is described and illustrated from Madagascar. The new genus shows morphological affinities to the Macropsini genus Galboa Distant recorded from Seychelles. A checklist of all known genera of Macropsinae is provided. PMID- 27389564 TI - Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. AB - BACKGROUND: Randomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting. METHODS: REBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models. RESULTS: Of 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12 month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis. CONCLUSION: The safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib. TRIAL REGISTRATION: Clinicaltrials.gov NCT02310477 . PMID- 27389565 TI - Effect of Transcatheter Mitral Annuloplasty With the Cardioband Device on 3 Dimensional Geometry of the Mitral Annulus. AB - This study was performed to assess the acute intraprocedural effects of transcatheter direct mitral annuloplasty using the Cardioband device on 3 dimensional (3D) anatomy of the mitral annulus. Of 45 patients with functional mitral regurgitation (MR) enrolled in a single arm, multicenter, prospective trial, 22 had complete pre- and post-implant 3D transesophageal echocardiography (TEE) images stored in native data format that allowed off-line 3D reconstruction. Images with the highest volume rate and best image quality were selected for analysis. Multiple measurements of annular geometry were compared from baseline to post-implant using paired t tests with Bonferroni correction to account for multiple comparisons. The device was successfully implanted in all patients, and MR was reduced to moderate in 2 patients, mild in 17 patients, and trace in 3 patients after final device cinching. Compared with preprocedural TEE, postprocedural TEE showed statistically significantly reductions in annular circumference (137 +/- 15 vs 128 +/- 17 mm; p = 0.042), intercommissural distance (42.4 +/- 4.3 vs 38.6 +/- 4.4 mm; p = 0.029), anteroposterior distance (40.0 +/- 5.4 vs 37.0 +/- 5.7 mm; p = 0.025), and aortic-mitral angle (117 +/- 8 degrees vs 112 +/- 8 degrees ; p = 0.032). This study demonstrates that transcatheter direct mitral annuloplasty with the Cardioband device results in acute remodeling of the mitral annulus with successful reduction of functional MR. PMID- 27389566 TI - Contemporary Burden of Atrial Fibrillation and Associated Mortality in Northeastern Italy. AB - Based on different estimation methods, mortality attributable to atrial fibrillation (AF) has been demonstrated to increase over time in developed countries, reaching a share ranging from 1% to 5% of overall deaths. To assess the whole burden of AF-associated mortality, all diseases mentioned in death certificates of subjects aged >=45 years resident in the Veneto Region (Northeastern Italy) were analyzed for the 2008 to 2013 period. The prevalence of common chronic co-morbidities was compared between deaths with mention of AF and a sample of age-matched deaths without reported AF. The disease was mentioned among conditions contributing to death in 25,834 subjects, corresponding to 9.8% of all regional deaths. Rates of AF-associated mortality were higher in men and increased steeply with age, being above 1 per 100 among residents aged >=85 years. Compared with non-AF-associated deaths, the strongest associations were observed between AF and hypertensive diseases (prevalence ratio 1.62, 95% CI 1.57 to 1.67), cardiac valve disorders (2.43, 2.25 to 2.61), cardiomyopathies (1.93, 1.70 to 2.19), cerebrovascular diseases (1.55, 1.50 to 1.60), and chronic obstructive pulmonary disease (1.49, 1.42 to 1.57). AF-associated mortality resulted higher than previously reported, probably due to aging of the population with multiple predisposing diseases, an increased recognition of AF among the elderly, and a raised awareness of certifying physicians about the importance of AF. Analyses of all diseases mentioned in death certificates underscored the interaction of AF with several other circulatory and respiratory disorders in pathologic networks leading to an increased risk of death. PMID- 27389567 TI - Pregnancy: part of life in chronic myelogenous leukemia. AB - Management of pregnant patients with chronic myelogenous leukemia (CML) is challenging. Some of the factors that need to be considered include stage of pregnancy, disease status, and degree of drug exposure. Managing a patient who has been diagnosed while pregnant requires a different approach as compared with a patient who becomes pregnant while on the treatment with a tyrosine kinase inhibitor (TKI). Younger patients may wish to conceive while on treatment and need a more personalized treatment plan based on the degree and duration of their molecular status. Leukapheresis and interferon are useful options in this situation due to teratogenic potential of TKIs. We present a series of clinical vignettes describing our approach to different scenarios and the management options employed in each case. Despite the era of TKIs and their undoubted efficacy and safety, situations such as these require an individualized and multidisciplinary approach to management. PMID- 27389569 TI - Neural network training as a dissipative process. AB - This paper analyzes the practical issues and reports some results on a theory in which learning is modeled as a continuous temporal process driven by laws describing the interactions of intelligent agents with their own environment. The classic regularization framework is paired with the idea of temporal manifolds by introducing the principle of least cognitive action, which is inspired by the related principle of mechanics. The introduction of the counterparts of the kinetic and potential energy leads to an interpretation of learning as a dissipative process. As an example, we apply the theory to supervised learning in neural networks and show that the corresponding Euler-Lagrange differential equations can be connected to the classic gradient descent algorithm on the supervised pairs. We give preliminary experiments to confirm the soundness of the theory. PMID- 27389568 TI - Lipid-based nanosystems for CD44 targeting in cancer treatment: recent significant advances, ongoing challenges and unmet needs. AB - Extensive experimental evidence demonstrates the important role of hyaluronic acid (HA)-CD44 interaction in cell proliferation and migration, inflammation and tumor growth. Taking advantage of this interaction, the design of HA-modified nanocarriers has been investigated for targeting CD44-overexpressing cells with the purpose of delivering drugs to cancer or inflammatory cells. The effect of such modification on targeting efficacy is influenced by several factors. In this review, we focus on the impact of HA-modification on the characteristics of lipid based nanoparticles. We try to understand how these modifications influence particle physicochemical properties, interaction with CD44 receptors, intracellular trafficking pathways, toxicity, complement/macrophage activation and pharmacokinetics. Our aim is to provide insight in tailoring particle modification by HA in order to design more efficient CD44-targeting lipid nanocarriers. PMID- 27389570 TI - Pointwise and uniform approximation by multivariate neural network operators of the max-product type. AB - In this article, the theory of multivariate max-product neural network (NN) and quasi-interpolation operators has been introduced. Pointwise and uniform approximation results have been proved, together with estimates concerning the rate of convergence. At the end, several examples of sigmoidal activation functions have been provided. PMID- 27389571 TI - Extreme learning machine and adaptive sparse representation for image classification. AB - Recent research has shown the speed advantage of extreme learning machine (ELM) and the accuracy advantage of sparse representation classification (SRC) in the area of image classification. Those two methods, however, have their respective drawbacks, e.g., in general, ELM is known to be less robust to noise while SRC is known to be time-consuming. Consequently, ELM and SRC complement each other in computational complexity and classification accuracy. In order to unify such mutual complementarity and thus further enhance the classification performance, we propose an efficient hybrid classifier to exploit the advantages of ELM and SRC in this paper. More precisely, the proposed classifier consists of two stages: first, an ELM network is trained by supervised learning. Second, a discriminative criterion about the reliability of the obtained ELM output is adopted to decide whether the query image can be correctly classified or not. If the output is reliable, the classification will be performed by ELM; otherwise the query image will be fed to SRC. Meanwhile, in the stage of SRC, a sub dictionary that is adaptive to the query image instead of the entire dictionary is extracted via the ELM output. The computational burden of SRC thus can be reduced. Extensive experiments on handwritten digit classification, landmark recognition and face recognition demonstrate that the proposed hybrid classifier outperforms ELM and SRC in classification accuracy with outstanding computational efficiency. PMID- 27389572 TI - Is the 90th Percentile Adequate? The Optimal Waist Circumference Cutoff Points for Predicting Cardiovascular Risks in 124,643 15-Year-Old Taiwanese Adolescents. AB - Adolescent obesity has increased to alarming proportions globally. However, few studies have investigated the optimal waist circumference (WC) of Asian adolescents. This study sought to establish the optimal WC cutoff points that identify a cluster of cardiovascular risk factors (CVRFs) among 15-year-old ethnically Chinese adolescents. This study was a regional population-based study on the CVRFs among adolescents who enrolled in all the senior high schools in Taipei City, Taiwan, between 2011 and 2014. Four cross-sectional health examinations of first-year senior high school (grade 10) students were conducted from September to December of each year. A total of 124,643 adolescents aged 15 (boys: 63,654; girls: 60,989) were recruited. Participants who had at least three of five CVRFs were classified as the high-risk group. We used receiver-operating characteristic curves and the area under the curve (AUC) to determine the optimal WC cutoff points and the accuracy of WC in predicting high cardiovascular risk. WC was a good predictor for high cardiovascular risk for both boys (AUC: 0.845, 95% confidence interval [CI]: 0.833-0.857) and girls (AUC: 0.763, 95% CI: 0.731 0.795). The optimal WC cutoff points were >=78.9 cm for boys (77th percentile) and >=70.7 cm for girls (77th percentile). Adolescents with normal weight and an abnormal WC were more likely to be in the high cardiovascular risk group (odds ratio: 3.70, 95% CI: 2.65-5.17) compared to their peers with normal weight and normal WC. The optimal WC cutoff point of 15-year-old Taiwanese adolescents for identifying CVRFs should be the 77th percentile; the 90th percentile of the WC might be inadequate. The high WC criteria can help health professionals identify higher proportion of the adolescents with cardiovascular risks and refer them for further evaluations and interventions. Adolescents' height, weight and WC should be measured as a standard practice in routine health checkups. PMID- 27389574 TI - Ankle fracture as a complication of hip arthroscopy: A case report. PMID- 27389573 TI - Renal pelvic and ureteral ultrasonographic characteristics of cats with chronic kidney disease in comparison with normal cats, and cats with pyelonephritis or ureteral obstruction. AB - Objectives The objective was to describe ultrasonographic characteristics of cats with stable chronic kidney disease (CKD) and determine if these were significantly different from cats with pyelonephritis (Pyelo) and ureteral obstruction (UO), to aid in clinical assessment during uremic crisis. Methods Sixty-six cats with stable CKD were prospectively enrolled, as well as normal control cats (n = 10), cats with a clinical diagnosis of Pyelo (n = 13) and cats with UO confirmed by surgical resolution (n = 11). Renal ultrasound was performed and routine still images and cine loops were obtained. Analysis included degree of pelvic dilation, and presence and degree of ureteral dilation. Measurements were compared between groups using non-parametric one-way ANOVA with Dunn's post hoc analysis. Results In total, 66.6% of CKD cats had measurable renal pelvic dilation compared with 30.0% of normal cats, 84.6% of Pyelo cats and 100% of UO cats. There was no statistically significant difference in renal pelvic widths between CKD cats and normal cats, or CKD cats and Pyelo cats. On almost all measurement categories, UO cats had significantly greater renal pelvic widths compared with CKD cats and normal cats ( P <0.05) but not Pyelo cats. Six percent of stable CKD cats had measurable proximal ureteral dilation on one or both sides vs 46.2% of Pyelo cats and 81.8% of UO cats. There was no statistically significant difference in proximal ureteral width between normal and CKD cats, or between Pyelo and UO cats. There was a statistically significant difference in proximal ureteral width between CKD and Pyelo cats, CKD and UO cats, normal and UO cats, and normal and Pyelo cats. Conclusions and relevance No significant difference in renal pelvic widths between CKD cats and Pyelo cats was seen. These data suggest CKD cats should have a baseline ultrasonography performed so that abnormalities documented during a uremic crisis can be better interpreted. PMID- 27389575 TI - A forest of creativity and a firing passion. PMID- 27389576 TI - ? PMID- 27389577 TI - Diffuse injury of the Papez circuit by focal head trauma: a diffusion tensor tractography study. PMID- 27389578 TI - Detection superiority of 7 T MRI protocol in patients with epilepsy and suspected focal cortical dysplasia. AB - In 11 adult patients with suspicion of Focal cortical dysplasia (FCD) on 1.5 T (n = 1) or 3 T (n = 10) magnetic resonance imaging (MRI), 7 T MRI was performed. Visibility, extent, morphological features and delineation were independently rated and subsequently discussed by three observers. Additionally, head-to-head comparisons with corresponding 3 T images were made in the eight patients with a previous 3 T MRI and sustained suspicion of FCD. Comparison with histopathology was done in the five patients that underwent surgery. All lesions, seen at 1.5 and 3 T, were also recognized on 7 T. At 7 T FLAIR highlighted the FCD-like lesions best, whereas T2 and T2* were deemed better suited to review structure and extent of the lesion. Image quality with the used 7 T MRI setup was higher than the quality with the used 3 T MRI setup. In 2 out of 11 patients diagnosis changed, in one after re-evaluation of the images, and in the other based on histopathology. With the used 7 T MRI setup, FCD-like lesions can be detected with more confidence and detail as compared to lower field strength. However, concordance between radiologic diagnosis and final diagnosis seems to be lower than expected. PMID- 27389579 TI - What is the publication rate for presentations given at the British Academic Conference in Otolaryngology (BACO)? AB - OBJECTIVES: The publication rate of some large academic meetings such as the American Academy of Otolaryngology-Head and Neck Surgery has been reported as 32%. We aimed to compare the rate of publication at the British Academic Conference in Otolaryngology (BACO) to allow surveillance of research activity in the United Kingdom (UK). DESIGN AND SETTING: The abstract records of both BACO 2009 and 2012 were examined. The MEDLINE database was searched using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and an iterative approach. We recorded time to publication as well as the authors' region and journal. MAIN OUTCOME MEASURES: publication rate by conference, region and journal. RESULTS: Twice the number of presentations were made at BACO 2012 (n = 814) compared to BACO 2009 (n = 387). Absolute numbers of publications were 158 in 2012 and 92 in 2009. Overall, the publication rate dropped from 24% overall in 2009 to 19% in 2012. This difference in proportions was not significant (P = 0.08). The number of abstracts accepted for BACO 2012 doubled from BACO 2009 in nearly every subspecialty category, except the general/training category, which trebled. For both conferences, head and neck was the largest subspecialty abstract category, as well as the largest subspecialty publication category. CONCLUSIONS: This study showed that the majority of abstracts presented at BACO 2009 and 2012 did not progress to publication. The rate of publication was similar to that seen in other general ENT meetings but do not compare favourably to the 69% rate seen for presentations made at the Otorhinolaryngological Research Society (ORS). The large increase in accepted abstracts at BACO 2012 may reflect growing competition for entry to specialist training. PMID- 27389580 TI - Nanoporous Gold Bowls: A Kinetic Approach to Control Open Shell Structures and Size-Tunable Lattice Strain for Electrocatalytic Applications. AB - Controlling sub-10 nm ligament sizes and open-shell structure in nanoporous gold (NPG) to achieve strained lattice is critical in enhancing catalytic activity, but it remains a challenge due to poor control of reaction kinetics in conventional dealloying approach. Herein, a ligament size-controlled synthesis of open-shell NPG bowls (NPGB) through hetero-epitaxial growth of NPGB on AgCl is reported. The ligament size in NPGB is controlled from 6 to 46 nm by varying the hydroquinone to HAuCl4 ratio. The Williamson-Hall analysis demonstrates a higher lattice strain in smaller ligament size. In particular, NPGB with 6 nm (NPGB 6) ligament size possess the highest strain of 15.4 * 10(-3) , which is nearly twice of conventional 2D NPG sheets (~8.8 * 10(-3) ). The presence of high surface energy facets in NPGBs is also envisaged. The best electrocatalytic activity toward methanol oxidation is observed in NPGB 6 (27.8 MUA MUg(-1) ), which is ~9 fold and 3-fold higher than 8 nm solid Au nanoparticles, and conventional NPG sheets. The excellent catalytic activity in NPGB 6 is attributed to the open shell structure, lattice strain, and higher electro-active surface area, allowing efficient exposure of catalytic active sites to facilitate the methanol oxidation. The results offer a potential strategy for designing next generation electrocatalysts. PMID- 27389581 TI - PrPC Undergoes Basal to Apical Transcytosis in Polarized Epithelial MDCK Cells. AB - The Prion Protein (PrP) is an ubiquitously expressed glycosylated membrane protein attached to the external leaflet of the plasma membrane via a glycosylphosphatidylinositol anchor (GPI). While the misfolded PrPSc scrapie isoform is the infectious agent of prion disease, the cellular isoform (PrPC) is an enigmatic protein with unclear function. Of interest, PrP localization in polarized MDCK cells is controversial and its mechanism of trafficking is not clear. Here we investigated PrP traffic in MDCK cells polarized on filters and in three-dimensional MDCK cysts, a more physiological model of polarized epithelia. We found that, unlike other GPI-anchored proteins (GPI-APs), PrP undergoes basolateral-to-apical transcytosis in fully polarized MDCK cells. Following this event full-length PrP and its cleavage fragments are segregated in different domains of the plasma membrane in polarized cells in both 2D and 3D cultures. PMID- 27389582 TI - Health related quality of life in patients with end stage kidney disease treated with haemodialysis in Malawi: a cross sectional study. AB - BACKGROUND: Haemodialysis in Malawi consumes a disproportionate amount of the national health budget, costing approximately $20,000 per patient per year. Adjunctive therapeutic agents for end stage kidney disease and laboratory services to measure standard dialysis outcomes are not routinely available. Therefore, alternative outcome measures of the efficacy of haemodialysis in Malawi are required. We measured health related quality of life of adult patients in Malawi treated with haemodialysis for end stage kidney disease. METHODS: We performed a cross-sectional study of patients receiving haemodialysis for end stage kidney disease at 4 dialysis centres in Malawi between 24/10/2012 and 30/11/012. Patients were included if they were >18 years of age and had been receiving haemodialysis for >3 months. We used the Kidney Disease Quality of Life Instrument Short Form to assess health related quality of life. RESULTS: We recruited 22 of 24 eligible patients (mean age 44.8 +/- 16.0 years, 59.1 % male, median duration on haemodialysis 12 months (Inter-quartile range 6-24 months)). Overall health related quality of life was low (mean score 59.9 +/- 8.8, maximum possible score 100) with the lowest scores recorded for physical health component summary score (50.4 +/- 22.8) compared to mental health component summary (61.3 +/- 23.0) and kidney disease component summary (67.9 +/- 13.2). Low household income (<$4000 per year) was associated with lower mental health component scores (adjusted r(2) = 0.413, p = 0.033). CONCLUSIONS: Quality of life of haemodialysis patients in Malawi can be easily measured using a validated questionnaire and provides an alternative and important measure of the efficacy of haemodialysis therapy. Physical health scores were particularly low and this may affect income generating capacity. Increased efforts are required to improve the quality of life of haemodialysis patients in Malawi with a particular focus on the burden of physical symptoms. PMID- 27389583 TI - Daily-Life Gait Quality as Predictor of Falls in Older People: A 1-Year Prospective Cohort Study. AB - Falls can have devastating consequences for older people. We determined the relationship between the likelihood of fall incidents and daily-life behavior. We used wearable sensors to assess habitual physical activity and daily-life gait quality (in terms of e.g. stability, variability, smoothness and symmetry), and determined their predictive ability for time-to-first-and-second-falls. 319 older people wore a trunk accelerometer (Dynaport MoveMonitor, McRoberts) during one week. Participants further completed questionnaires and performed grip strength and trail making tests to identify risk factors for falls. Their prospective fall incidence was followed up for six to twelve months. We determined interrelations between commonly used gait characteristics to gain insight in their interpretation and determined their association with time-to-falls. For all data including questionnaires and tests- we determined the corresponding principal components and studied their predictive ability for falls. We showed that gait characteristics of walking speed, stride length, stride frequency, intensity, variability, smoothness, symmetry and complexity were often moderately to highly correlated (r > 0.4). We further showed that these characteristics were predictive of falls. Principal components dominated by history of falls, alcohol consumption, gait quality and muscle strength proved predictive for time-to-fall. The cross-validated prediction models had adequate to high accuracy (time dependent AUC of 0.66-0.72 for time-to-first-fall and 0.69-0.76 for -second fall). Daily-life gait quality obtained from a single accelerometer on the trunk is predictive for falls. These findings confirm that ambulant measurements of daily behavior contribute substantially to the identification of elderly at (high) risk of falling. PMID- 27389585 TI - Your critical care patient may have HLH (hemophagocytic lymphohistiocytosis). PMID- 27389584 TI - Metarhizium brunneum Blastospore Pathogenesis in Aedes aegypti Larvae: Attack on Several Fronts Accelerates Mortality. AB - Aedes aegypti is the vector of a wide range of diseases (e.g. yellow fever, dengue, Chikungunya and Zika) which impact on over half the world's population. Entomopathogenic fungi such as Metarhizium anisopliae and Beauveria bassiana have been found to be highly efficacious in killing mosquito larvae but only now are the underlying mechanisms for pathogenesis being elucidated. Recently it was shown that conidia of M. anisopliae caused stress induced mortality in Ae. aegypti larvae, a different mode of pathogenicity to that normally seen in terrestrial hosts. Blastospores constitute a different form of inoculum produced by this fungus when cultured in liquid media and although blastospores are generally considered to be more virulent than conidia no evidence has been presented to explain why. In our study, using a range of biochemical, molecular and microscopy methods, the infection process of Metarhizium brunneum (formerly M. anisopliae) ARSEF 4556 blastospores was investigated. It appears that the blastospores, unlike conidia, readily adhere to and penetrate mosquito larval cuticle. The blastospores are readily ingested by the larvae but unlike the conidia are able infect the insect through the gut and rapidly invade the haemocoel. The fact that pathogenicity related genes were upregulated in blastospores exposed to larvae prior to invasion, suggests the fungus was detecting host derived cues. Similarly, immune and defence genes were upregulated in the host prior to infection suggesting mosquitoes were also able to detect pathogen-derived cues. The hydrophilic blastospores produce copious mucilage, which probably facilitates adhesion to the host but do not appear to depend on production of Pr1, a cuticle degrading subtilisin protease, for penetration since protease inhibitors did not significantly alter blastospore virulence. The fact the blastospores have multiple routes of entry (cuticle and gut) may explain why this form of the inoculum killed Ae. aegypti larvae in a relatively short time (12-24hrs), significantly quicker than when larvae were exposed to conidia. This study shows that selecting the appropriate form of inoculum is important for efficacious control of disease vectors such as Ae. aegypti. PMID- 27389586 TI - Epigenetic regulation of TGF-beta1 signalling in dilative aortopathy of the thoracic ascending aorta. AB - The term 'epigenetics' refers to heritable, reversible DNA or histone modifications that affect gene expression without modifying the DNA sequence. Epigenetic modulation of gene expression also includes the RNA interference mechanism. Epigenetic regulation of gene expression is fundamental during development and throughout life, also playing a central role in disease progression. The transforming growth factor beta1 (TGF-beta1) and its downstream effectors are key players in tissue repair and fibrosis, extracellular matrix remodelling, inflammation, cell proliferation and migration. TGF-beta1 can also induce cell switch in epithelial-to-mesenchymal transition, leading to myofibroblast transdifferentiation. Cellular pathways triggered by TGF-beta1 in thoracic ascending aorta dilatation have relevant roles to play in remodelling of the vascular wall by virtue of their association with monogenic syndromes that implicate an aortic aneurysm, including Loeys-Dietz and Marfan's syndromes. Several studies and reviews have focused on the progression of aneurysms in the abdominal aorta, but research efforts are now increasingly being focused on pathogenic mechanisms of thoracic ascending aorta dilatation. The present review summarizes the most recent findings concerning the epigenetic regulation of effectors of TGF-beta1 pathways, triggered by sporadic dilative aortopathy of the thoracic ascending aorta in the presence of a tricuspid or bicuspid aortic valve, a congenital malformation occurring in 0.5-2% of the general population. A more in-depth comprehension of the epigenetic alterations associated with TGF-beta1 canonical and non-canonical pathways in dilatation of the ascending aorta could be helpful to clarify its pathogenesis, identify early potential biomarkers of disease, and, possibly, develop preventive and therapeutic strategies. PMID- 27389587 TI - Exercise-induced mitochondrial dysfunction: a myth or reality? AB - Beneficial effects of physical activity on mitochondrial health are well substantiated in the scientific literature, with regular exercise improving mitochondrial quality and quantity in normal healthy population, and in cardiometabolic and neurodegenerative disorders and aging. However, several recent studies questioned this paradigm, suggesting that extremely heavy or exhaustive exercise fosters mitochondrial disturbances that could permanently damage its function in health and disease. Exercise-induced mitochondrial dysfunction (EIMD) might be a key proxy for negative outcomes of exhaustive exercise, being a pathophysiological substrate of heart abnormalities, chronic fatigue syndrome (CFS) or muscle degeneration. Here, we overview possible factors that mediate negative effects of exhaustive exercise on mitochondrial function and structure, and put forward alternative solutions for the management of EIMD. PMID- 27389589 TI - Sex and gender differences in HIV-1 infection. AB - The major burden of the human immunodeficiency (HIV) type 1 pandemic is nowadays carried by women from sub-Saharan Africa. Differences in the manifestations of HIV-1 infection between women and men have been long reported, and might be due to both socio-economic (gender) and biological (sex) factors. Several studies have shown that women are more susceptible to HIV-1 acquisition than men. Following HIV-1 infection, women have lower viral loads during acute infection and exhibit stronger antiviral responses than men, which may contribute to differences in the size of viral reservoirs. Oestrogen receptor signalling could represent an important mediator of sex differences in HIV-1 reservoir size and may represent a potential therapeutic target. Furthermore, immune activation, a hallmark of HIV-1 infection, is generally higher in women than in men and could be a central mechanism in the sex difference observed in the speed of HIV-1 disease progression. Here, we review the literature regarding sex-based differences in HIV-1 infection and discuss how a better understanding of the underlying mechanisms could improve preventive and therapeutic strategies. PMID- 27389590 TI - Transcriptome sequencing reveals genetic mechanisms underlying the transition between the laying and brooding phases and gene expression changes associated with divergent reproductive phenotypes in chickens. AB - Transition from laying to incubation behavior in chicken is an interesting topic in reproductive biology. The decline of incubation behavior in chicken population has led to considerable phenotypic differences in reproductive traits between breeds. However, the exact genetic mechanism of the reproductive phase transition still largely unknown and little is known about the gene expression changes that contribute to the phenotypic differences. We performed mRNA sequencing to investigate the molecular mechanism underlying the transition from laying to brooding and to detect difference in gene regulation underlying the phenotypic diversification using two chicken breeds. The majority of gene expression changes during phase transition were steroidogenesis and hormone-releasing genes. Brooding chickens shared a conservative pattern of greatly inhibited steroidogenic enzyme genes in the pituitary gland, therefore, low levels of steroidogenic enzymes might result in reproductive defects such as ovary regression and brooding onset. The conserved network responsible for brooding behavior was maintained by steroid biosynthesis and hormonal interactions. Interestingly, three transcription factors, SREBF2, NR5A1 and PGR, act as central signal modulators of steroid biosynthesis and hormonal interactions during the transition from laying to brooding modes at the molecular level. Furthermore, Genes correlated with protein synthesis and accumulation showed expression variation between breeds, which might result in different concentrations of and sensitivities to reproduction-related hormones. This study provided a new insight in neuroendocrine system at the molecular level, and helps to understand the genetic and hormonal responses that ultimately translate into behavior in chicken. PMID- 27389592 TI - Correction to "Free Energy Reconstruction in Bidirectional Force Spectroscopy Experiments: The Effect of the Device Stiffness". PMID- 27389591 TI - TRS-PCR profiling for discrimination of Escherichia coli strains isolated from children with diarrhea under 5 years of age in Lodz region, Poland. AB - Escherichia coli is one of the most frequently isolated gram-negative pathogens in cases of foodborne diseases and hospital infections. What is more, diarrheal diseases, including these associated with pathogenic E. coli strains, are leading causes of morbidity and mortality worldwide, especially among children. Improvements of the management of diarrheal diseases caused by these bacteria are in the spotlight of the World Health Organization. Therefore, there is still a need to develop new methods or improve ones that are commonly used to characterize and distinguish E. coli strains more precisely. In this work, TRS based PCRs were effectively used for discrimination of 123 E. coli strains isolated from children with diarrhea in the Lodz region (Poland). The composite TRS-PCR approach, based on similarity comparisons of GTG-PCR and CGG-PCR fingerprints, enabled us to distinguish strains with very good efficacy. This was confirmed by the high diversity index (0.991) and high reproducibility of the band patterns obtained (95.0 %). These results showed the great variation in strains that may cause infections in children under 38 months. However, the stains were grouped in three separate clusters, which were different in terms of their phylogenetic affiliation and virulence factor repertoire. The obtained results support and are consistent with the need of public health surveillance for searching new and fast assays as far as children's health is concerned. TRS PCR profiling is an effective tool for genotyping of E. coli strains isolated from children with diarrhea. PMID- 27389588 TI - Preeclampsia and the brain: neural control of cardiovascular changes during pregnancy and neurological outcomes of preeclampsia. AB - Preeclampsia (PE) is a form of gestational hypertension that complicates ~5% of pregnancies worldwide. Over 70% of the fatal cases of PE are attributed to cerebral oedema, intracranial haemorrhage and eclampsia. The aetiology of PE originates from abnormal remodelling of the maternal spiral arteries, creating an ischaemic placenta that releases factors that drive the pathophysiology. An initial neurological outcome of PE is the absence of the autonomically regulated cardiovascular adaptations to pregnancy. PE patients exhibit sympathetic overactivation, in comparison with both normotensive pregnant and hypertensive non-pregnant females. Moreover, PE diminishes baroreceptor reflex sensitivity (BRS) beyond that observed in healthy pregnancy. The absence of the cardiovascular adaptations to pregnancy, combined with sympathovagal imbalance and a blunted BRS leads to life-threatening neurological outcomes. Behaviourally, the increased incidences of maternal depression, anxiety and post-traumatic stress disorder (PTSD) in PE are correlated to low fetal birth weight, intrauterine growth restriction (IUGR) and premature birth. This review addresses these neurological consequences of PE that present in the gravid female both during and after the index pregnancy. PMID- 27389593 TI - Impact of bleaching agents on water sorption and solubility of resin luting cements. AB - AIM: The aim of the present study was to evaluate the effect of distilled water and home and office bleaching agents on the sorption and solubility of resin luting cements. METHODS: A total of 18 disc-shaped specimens were prepared from each of four resin cements: G-CEM LinkAce, Panavia F, Rely X Unicem, and seT. Specimens were cured according to the manufacturers' instructions and randomly divided into three groups of six, where they were treated with either an office or home bleaching agent or immersed in distilled water (control). Water sorption and solubility were measured by weighing the specimens before and after immersion and desiccation. Data were analyzed using Pearson correlation coefficient, two way analysis of variance (ANOVA) and Tukey's test. RESULTS: There was a significant, positive correlation between sorption and solubility. Two-way anova showed significant differences among all resin cements tested for either sorption or solubility. Water sorption and solubility of all cements were affected significantly by office bleaching, and even more by home bleaching agents. CONCLUSIONS: Sorption and solubility behavior of the studied cements were highly correlated and significantly affected by applying either office or home bleaching agents; seT showed the highest sorption and solubility, whereas Rely X Unicem revealed the lowest. PMID- 27389594 TI - Genetic Landscape of Sporadic Unilateral Adrenocortical Adenomas Without PRKACA p.Leu206Arg Mutation. AB - CONTEXT: Adrenocortical adenomas (ACAs) are among the most frequent human neoplasias. Genetic alterations affecting the cAMP/protein kinase A signaling pathway are common in cortisol-producing ACAs, whereas activating mutations in the gene encoding beta-catenin (CTNNB1) have been reported in a subset of both benign and malignant adrenocortical tumors. However, the molecular pathogenesis of most ACAs is still largely unclear. OBJECTIVE: The aim of the study was to define the genetic landscape of sporadic unilateral ACAs. DESIGN AND SETTING: Next-generation whole-exome sequencing was performed on fresh-frozen tumor samples and corresponding normal tissue samples. PATIENTS: Ninety-nine patients with ACAs (74 cortisol-producing and 25 endocrine inactive) negative for p.Leu206Arg PRKACA mutation. MAIN OUTCOME MEASURES: Identification of known and/or new genetic alterations potentially involved in adrenocortical tumorigenesis and autonomous hormone secretion, genotype-phenotype correlation. RESULTS: A total of 706 somatic protein-altering mutations were detected in 88 of 99 tumors (median, six per tumor). We identified several mutations in genes of the cAMP/protein kinase A pathway, including three novel mutations in PRKACA, associated with female sex and Cushing's syndrome. We also found genetic alterations in different genes involved in the Wnt/beta-catenin pathway, associated with larger tumors and endocrine inactivity, and notably, in many genes of the Ca(2+)-signaling pathway. Finally, by comparison of our genetic data with those available in the literature, we describe a comprehensive genetic landscape of unilateral ACAs. CONCLUSIONS: This study provides the largest sequencing effort on ACAs to date. We thereby identified somatic alterations affecting known and novel pathways potentially involved in adrenal tumorigenesis. PMID- 27389596 TI - "Reliability generalization of the Multigroup Ethnic Identity Measure-Revised (MEIM-R)": Correction to Herrington et al. (2016). AB - Reports an error in "Reliability Generalization of the Multigroup Ethnic Identity Measure-Revised (MEIM-R)" by Hayley M. Herrington, Timothy B. Smith, Erika Feinauer and Derek Griner (Journal of Counseling Psychology, Advanced Online Publication, Mar 17, 2016, np). The name of author Erika Feinauer was misspelled as Erika Feinhauer. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2016-13160-001.) Individuals' strength of ethnic identity has been linked with multiple positive indicators, including academic achievement and overall psychological well-being. The measure researchers use most often to assess ethnic identity, the Multigroup Ethnic Identity Measure (MEIM), underwent substantial revision in 2007. To inform scholars investigating ethnic identity, we performed a reliability generalization analysis on data from the revised version (MEIM-R) and compared it with data from the original MEIM. Random-effects weighted models evaluated internal consistency coefficients (Cronbach's alpha). Reliability coefficients for the MEIM-R averaged alpha = .88 across 37 samples, a statistically significant increase over the average of alpha = .84 for the MEIM across 75 studies. Reliability coefficients for the MEIM-R did not differ across study and participant characteristics such as sample gender and ethnic composition. However, consistently lower reliability coefficients averaging alpha = .81 were found among participants with low levels of education, suggesting that greater attention to data reliability is warranted when evaluating the ethnic identity of individuals such as middle-school students. Future research will be needed to ascertain whether data with other measures of aspects of personal identity (e.g., racial identity, gender identity) also differ as a function of participant level of education and associated cognitive or maturation processes. (PsycINFO Database Record PMID- 27389595 TI - Nationwide Trends in Hospitalizations and In-Hospital Mortality in Granulomatosis With Polyangiitis (Wegener's). AB - OBJECTIVE: Granulomatosis with polyangiitis (Wegener's) (GPA) is a type of antineutrophil cytoplasmic antibody-associated vasculitis that often entails severe end-organ damage and treatment-related complications that frequently lead to hospitalization and death. Nationwide trends in hospitalizations and in hospital mortality over the past 2 decades are unknown and were evaluated in this study. METHODS: Using the National Inpatient Sample, the largest all-payer inpatient database in the US, trends in hospitalizations with a discharge diagnosis of GPA (formerly Wegener's granulomatosis; International Classification of Disease, Ninth Revision, Clinical Modification code 446.4) between 1993 and 2011 were studied. Analyses were performed using hospital-level sampling weights to obtain US national estimates. RESULTS: From 1993 to 2011, the annual hospitalization rate for patients with a principal diagnosis of GPA increased by 24%, from 5.1 to 6.3 per 1 million US persons (P < 0.0001 for trend); however, in hospital deaths in this group declined by 73%, from 9.1% to 2.5% (P < 0.0001 for trend), resulting in a 66% net reduction in the annual in-hospital mortality rate. The median length of stay declined by 20%, from 6.9 days in 1993 to 5.5 days in 2011 (P = 0.0002 for trend). Infection was the most common principal discharge diagnosis when GPA was a secondary diagnosis, including among those who died during hospitalization. CONCLUSION: The findings from these nationally representative, contemporary inpatient data indicate that the in-hospital mortality of GPA has declined substantially over the past 2 decades, while the overall hospitalization rate for GPA increased slightly. Infection remains a common principal hospitalization diagnosis among GPA patients, including hospitalizations resulting in mortality. PMID- 27389597 TI - [Analysis of the German state medical examination regarding psychiatrically relevant topics]. AB - BACKGROUND: The second part of the state medical examination is an essential part of medical education in Germany. From 2006 until 2013, the second and third parts of the licensing examination were combined, thus earning this examination the reputation of being notoriously difficult to pass. The aim of this exploratory study was to examine psychiatric and psychotherapeutic questions in the written part of the second examination. OBJECTIVES: This study analyzed the proportion of psychiatric and psychotherapeutic questions in the written part of the second leg of the German state medical examination. In a second step, a more detailed analysis aimed to identify more specific subject areas and to allocate diagnoses according to ICD-10, allowing a detailed overview of the presence of psychiatric topics. MATERIAL AND METHODS: A total of 8 examinations from fall 2010 up to spring 2014 a were included in the analysis. Every examination comprised 320 questions, thus a total of 2560 questions were analyzed. All questions pertaining to psychiatric or psychotherapeutic topics were included. Questions were categorized according to a predefined set of subject areas and an ICD-10 diagnosis. RESULTS: Out of the total of 2560 questions analyzed, 166 were categorized as being in psychiatry or psychotherapy, with each examination comprising an average of 20.75 (SD = 5.80) relevant questions. Most questions were allocated to the subject area of pharmacology (n = 53), followed by psychopathologic assessment (n = 27) and psychotherapy (n = 12). Sorted according to ICD-10 criteria, most questions could be assigned to the F3 category, the affective disorders group (21.9 %, n = 35). CONCLUSION: In comparison to the actual strain placed on the healthcare system, the results indicate an underrepresentation of psychiatric disorders in the second part of the German state medical examination. The distribution of specific disorders mirrors the actual distribution at least in part; however, certain practically relevant disorders are severely underrepresented. PMID- 27389598 TI - [Cell depletion and myoablation for neuroimmunological diseases]. AB - BACKGROUND: The treatment of autoimmune disorders of the nervous system is based on interventions for the underlying immune phenomena. OBJECTIVE: To summarize concepts of cell depletion and myeloablation studied in the context of neuroimmunological disorders. METHOD: Evaluation of the available literature on multiple sclerosis as the most widely studied neuroimmunological entity. RESULTS: Three concepts have been introduced: classical immunosuppressants, such as azathioprine, mitoxantrone and cyclophosphamide exert general lymphopenic effects and thereby moderately decrease disease activity. Myeloablative regimens combined with autologous hematopoietic stem cell transplantation have a profound and in most cases long-lasting impact on autoimmunity at the cost of potentially life threatening side effects. Alemtuzumab (anti-CD52), rituximab and ocrelizumab (both anti-CD20) are depleting antibodies directed against certain lymphocyte subsets and substantially ameliorate disease activity in relapsing-remitting multiple sclerosis. Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis. CONCLUSIONS: Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks. In the context of the increasing number of alternative immunomodulatory options the indications for use should be cautiously considered. PMID- 27389599 TI - [Invasive stimulation procedures and EEG diagnostics in epilepsy]. AB - Stimulation has been performed experimentally and in small case series to treat epilepsy since the 1970s. Since the introduction of vagus nerve stimulation in 1997 and intracranial stimulation methods in 2011 into patient care, invasive stimulation has become a rapidly developing but infrequently used therapeutic option in Europe. Whereas vagus nerve stimulation is frequently used, particularly in the USA, intracranial stimulation differs in its regional availability. In order to improve the efficacy of stimulation, develop criteria for its use and assure low complication rates, a concentration on experienced centers and multicenter data acquisition and sharing are needed.Invasive electroencephalographic (EEG) monitoring with subdural electrodes and especially with stereotactically implanted depth electrodes have been used increasingly more often for presurgical evaluation in recent years. They are applied when non invasive diagnostics show insufficient results to exactly identify the location and extent of the epileptogenic zone or cannot be adequately distinguished from eloquent cortex areas. Complications include intracranial hemorrhage, infections and increased intracranial pressure but lasting deficits or even death are rare (<=2 %). The outcome of invasive monitoring is inferior to non-invasive monitoring because of the higher degree of complexity of the cases; however, it is far superior to the seizure-free rates achieved by anticonvulsant drug treatment alone. PMID- 27389600 TI - [Brivaracetam for add-on treatment in focal epilepsy]. AB - Brivaracetam is the latest antiepileptic drug to be approved for adjunctive therapy in focal epilepsy and has a high affinity as a SV2A ligand. The aim of this review article is to summarize the data from the pivotal studies in which more than 2000 patients received brivaracetam. A significant median reduction in seizures from 30.5 % to 53.1 % for 50 mg/day, from 32.5 % to 37.2 % for 100 mg/day and 35.6 % for 200 mg/day could be demonstrated. Overall brivaracetam appears to be well-tolerated, with fatigue, dizziness and somnolence being the main adverse side effects. An immediate change from levetiracetam to brivaracetam at a conversion ratio of 10:1 to 15:1 seems feasible and could alleviate behavioral side effects related to treatment with levetiracetam. A swift permeability into brain tissue and a faster onset of action compared to levetiracetam suggest that brivaracetam could be useful in emergency situations. PMID- 27389601 TI - [Cellular replacement strategies and adult neurogenesis in idiopathic Parkinson's disease]. AB - Parkinson's disease (PD) is the most common age-related movement disorder and characterized by slowly progressive neurodegeneration resulting in motor symptoms, such as bradykinesia, rigidity, tremor and postural instability. Moreover, non-motor symptoms, such as hyposmia, anxiety and depression reduce the quality of life in PD. Motor symptoms are associated with a distinct striatal dopaminergic deficit resulting from axonal dysfunction and neuronal loss in the substantia nigra (SN). Recent progress in stem cell technology allows the optimization of cellular transplantation strategies in order to alleviate the motor deficit, which potentially leads to a reactivation of this therapeutic strategy. Besides neurodegenerative processes impaired adult neurogenesis and consequentially reduced endogenous cellular plasticity may play an important role in PD. This article discusses the notion that non-motor symptoms in PD may partly be explained by reduced adult neurogenesis in the olfactory bulb and hippocampus. PMID- 27389602 TI - [Hermann Oppenheim. Comments on his life and works]. AB - The outstanding neurologist Hermann Oppenheim was renowned worldwide during his lifetime and was highly esteemed; however, he was also a contradictory, complex personality and his life was marked by several tragic events. Even for his contemporaries, his life and work was the subject of lively discussions and debates and also some 100 years later, it is an interesting challenge to obtain an insight into the extensive work of this famous man and to understand the reasons for his great successes and failures. PMID- 27389603 TI - Control of the Handedness of Self-assemblies of Dipeptides by the Chirality of Phenylalanine and Steric Hindrance of Phenylglycine. AB - Eight dipeptides, composed of phenylalanine and phenylglycine, that are able to self-assemble into twisted nanoribbons in deionized water are synthesized. The handedness of the nanoribbons is controlled by the chirality of the phenylalanine and the steric hindrance owing to the phenyl group of the phenylglycine. When the phenylalanine is at the C-terminal, pi-pi stacking by the phenyl groups, hydrogen bonding by the NH group of the phenylalanine, and hydrophobic associations of the alkyl chains control the stacking of the molecules. When phenylglycine is at the C-terminal, the chiral pi-pi stacking by the phenyl groups of the phenylalanines is suppressed. The hydrogen bonds formed by the NH groups of the phenylalanines had a greater contribution on forming organic self-assemblies than those formed by the NH groups of the phenylglycines. PMID- 27389604 TI - Knowledge of the Unknown Child: A Systematic Review of the Elements of the Best Interests of the Child Assessment for Recently Arrived Refugee Children. AB - Decision-making regarding an asylum request of a minor requires decision-makers to determine the best interests of the child when the minor is relatively unknown. This article presents a systematic review of the existing knowledge of the situation of recently arrived refugee children in the host country. This research is based on the General Comment No. 14 of UN Committee on the Rights of the Child. It shows the importance of knowing the type and number of stressful life events a refugee child has experienced before arrival, as well as the duration and severity of these events. The most common mental health problems children face upon arrival in the host country are PTSD, depression and various anxiety disorders. The results identify the relevant elements of the best interests of the child assessment, including implications for procedural safeguards, which should promote a child rights-based decision in the asylum procedure. PMID- 27389605 TI - Parenting Cognition and Affective Outcomes Following Parent Management Training: A Systematic Review. AB - Parent management training (PMT) is considered the gold standard in the treatment of child behavior problems. The secondary effects of these interventions, particularly on parent well-being, are infrequently studied, despite evidence that parents of children with behavior problems often experience personal difficulties. This narrative review examined the affective and parenting cognition outcomes of PMT for mothers and fathers of children ages 2-13 years, across 48 controlled treatment studies. Substantial support was found for reductions in parenting stress, and increases in perceived parenting competence following PMT. Evidence indicated fewer improvements in domains more distal from parenting, including parent depressive symptoms and marital relationship dysfunction. A number of studies suggested parent gender as a moderator of parent outcomes of PMT; however, the underrepresentation of fathers in existing research limits conclusions in this regard. Avenues for future research are highlighted to address current gaps in the literature, and to further our understanding of the ways in which both children and parents may benefit from PMT. PMID- 27389607 TI - Bolstering the pipeline for primary care: a proposal from stakeholders in medical education. AB - The Association of American Medical Colleges reports an impending shortage of over 90,000 primary care physicians by the year 2025. An aging and increasingly insured population demands a larger provider workforce. Unfortunately, the supply of US-trained medical students entering primary care residencies is also dwindling, and without a redesign in this country's undergraduate and graduate medical education structure, there will be significant problems in the coming decades. As an institution producing fewer and fewer trainees in primary care for one of the poorest states in the United States, we propose this curriculum to tackle the issue of the national primary care physician shortage. The aim is to promote more recruitment of medical students into family medicine through an integrated 3-year medical school education and a direct entry into a local or state primary care residency without compromising clinical experience. Using the national primary care deficit figures, we calculated that each state medical school should reserve 20-30 primary care (family medicine) residency spots, allowing students to bypass the traditional match after successfully completing a series of rigorous externships, pre-internships, core clerkships, and board exams. Robust support, advising, and personal mentoring are also incorporated to ensure adequate preparation of students. The nation's health is at risk. With full implementation in allopathic medical schools in 50 states, we propose a long term solution that will serve to provide more than 1,000-2,700 new primary care providers annually. Ultimately, we will produce happy, experienced, and empathetic doctors to advance our nation's primary care system. PMID- 27389608 TI - [Polymorphic lesions of cutaneous leishmaniasis revealing human immunodeficiency virus infection]. PMID- 27389609 TI - Applying theoretical premises of binary toxicity mathematical modeling to combined impacts of chemical plus physical agents (A case study of moderate subchronic exposures to fluoride and static magnetic field). AB - Sodium fluoride solution was injected i.p. to rats at a dose equivalent to 0.1 LD50 three times a week up to 18 injections. Two thirds of these rats and of the sham-injected ones were exposed to the whole body impact of a 25 mT static magnetic field for 2 or 4 h a day, 5 times a week. For mathematical analysis of the effects they produced in combination, we used a response surface model. This analysis demonstrated that (like in combined toxicity) the combined adverse action of a chemical plus a physical agent was characterized by a diversity of types depending not only on particular effects these types were assessed for but on their level as well. From this point of view, the indices for which at least one statistically significant effect was observed could be classified as identifying (1) single-factor action; (2) additivity; (3) synergism; (4) antagonism (both subadditive unidirectional action and all variants of contradirectional action). Although the classes (2) and (3) taken together encompass a smaller part of the indices, the biological importance of some of them renders the combination of agents studied as posing a higher health risk than that associated with each them acting alone. PMID- 27389606 TI - Distilling Common History and Practice Elements to Inform Dissemination: Hanf Model BPT Programs as an Example. AB - There is a shift in evidence-based practice toward an understanding of the treatment elements that characterize empirically supported interventions in general and the core components of specific approaches in particular. The evidence base for behavioral parent training (BPT) and the standard of care for early-onset disruptive behavior disorders (oppositional defiant disorder and conduct disorder), which frequently co-occur with attention deficit hyperactivity disorder, are well established, yet an ahistorical, program-specific lens tells little regarding how leaders, University of Oregon Medical School, shaped the common practice elements of contemporary evidence-based BPT. Accordingly, this review summarizes the formative work of Hanf, as well as the core elements, evolution, and extensions of her work, represented in Community Parent Education (COPE; (Cunningham et al. in J Child Psychol Psychiatry 36:1141-1159, 1995; Cunningham et al. in COPE, the community parent education program: large group community-based workshops for parents of 3- to 18-year-olds, COPE Works, Hamilton, 2009), Defiant Children (DC; (Barkley in Defiant children: a clinician's manual for assessment and parent training, Guilford Press, New York, 1987; Barkley in Defiant children: a clinician's manual for assessment and parent training, Guilford Press, New York, 2013), Helping the Noncompliant Child (HNC; Forehand and McMahon in Helping the noncompliant child: a clinician's guide to parent training, Guilford Press, New York, 1981; McMahon and Forehand in Helping the noncompliant child: family-based treatment for oppositional behavior, 2nd ed., Guilford Press, New York, 2003), Parent-child interaction therapy (PCIT; Eyberg and Robinson in J Clin Child Adolesc Psychol 11:130-137, 1982. doi:10.1080/15374418209533076; Eyberg in Child Fam Behav Ther 10:33-46, 1988; Eyberg and Funderburk in Parent-child interaction therapy protocol, PCIT International, Gainesville, 2011), and the Incredible Years (IY; (Webster Stratton in Behav Ther 12:634-642, 1981. doi:10.1016/S0005-7894(81)80135-9; Webster-Stratton in J Pediatr Psychol 7:279-294, 1982. doi:10.1093/jpepsy/7.3.279; Webster-Stratton in The incredible years: parents and children series. Leader's guide: preschool version of BASIC (ages 3-6 years, The Incredible Years, Seattle, 2008). Our goal is not to provide an exhaustive review of the evidence base for the Hanf-Model programs, rather our intention is to provide a template of sorts from which agencies and clinicians can make informed choices about how and why they are using one program versus another, as well as how to make inform flexible use one program or combination of practice elements across programs, to best meet the needs of child clients and their families. Clinical implications and directions for future work are discussed. PMID- 27389610 TI - Prevention of Vitamin K Deficiency Bleeding. AB - The risk that a newborn will develop vitamin K deficiency bleeding is 1700/100,000 (one out of 59) if vitamin K is not administered. When intramuscular vitamin K is administered, the risk of vitamin K deficiency bleeding is reduced to 1/100,000. While women may have misconceptions about vitamin K prophylaxis for their newborns, health care providers should be prepared with factual information. Prophylaxis is needed even for healthy newborns without risk factors for bleeding. Other forms of vitamin K supplementation, including oral administration of Food and Drug Administration-approved vitamin K preparations and maternal supplements during pregnancy or lactation, do not have the same effectiveness as the parenteral form. The formulations of vitamin K approved for use in the United States have not been associated with childhood leukemia or other childhood health problems. Care providers need to give accurate information to families regarding the risks and benefits of vitamin K prophylaxis. An interprofessional approach to education can be effective in increasing acceptance of vitamin K prophylaxis and decreasing the incidence of vitamin K deficiency bleeding. This article uses a case study approach to highlight common misconceptions about vitamin K prophylaxis and discuss a recent interprofessional collaboration to prevent vitamin K deficiency bleeding. PMID- 27389611 TI - Transdermal thiol-acrylate polyethylene glycol hydrogel synthesis using near infrared light. AB - Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm(-2)) could induce gelation via a mixed-mode reaction with a small increase in temperature (~5 degrees C) under the optimized conditions. We also achieved successful transdermal gelation via the NIR-assisted photothermal thiol-acryl reactions. This new type of NIR-assisted thiol-acrylate polymerization provides new opportunities for in situ hydrogel formation for injectable hydrogels and delivery of drugs/cells for various biomedical applications. PMID- 27389612 TI - Characterization of reactive flow-induced evolution of carbonate rocks using digital core analysis- part 1: Assessment of pore-scale mineral dissolution and deposition. AB - The application of X-ray micro-computed tomography (MU-CT) for quantitatively characterizing reactive-flow induced pore structure evolution including local particle detachment, displacement and deposition in carbonate rocks is investigated. In the studies conducted in this field of research, the experimental procedure has involved alternating steps of imaging and ex-situ core sample alteration. Practically, it is impossible to return the sample, with micron precision, to the same position and orientation. Furthermore, successive images of a sample in pre- and post-alteration states are usually taken at different conditions such as different scales, resolutions and signal-to-noise ratios. These conditions accompanying with subresolution features in the images make voxel-by-voxel comparisons of successive images problematic. In this paper, we first address the respective challenges in voxel-wise interpretation of successive images of carbonate rocks subject to reactive flow. Reactive coreflood in two carbonate cores with different rock types are considered. For the first rock, we used the experimental and imaging results published by Qajar et al. (2013) which showed a quasi-uniform dissolution regime. A similar reactive core flood was conducted in the second rock which resulted in wormhole-like dissolution regime. We particularly examine the major image processing operations such as transformation of images to the same grey-scale, noise filtering and segmentation thresholding and propose quantitative methods to evaluate the effectiveness of these operations in voxel-wise analysis of successive images of a sample. In the second part, we generalize the methodology based on the three phase segmentation of normalized images, microporosity assignment and 2D histogram of image intensities to estimate grey-scale changes of individual image voxels for a general case where the greyscale images are segmented into arbitrary number of phases. The results show that local (voxel-based) porosity changes can be decomposed into local mineral dissolution and deposition. Moreover, it is found that the microporosity evolutions are differently distributed in the samples after the reactive coreflood experiments. In the last part of the paper, for the case of quasi-uniform dissolution, we combine the tomographic images with numerical calculations of permeability along the core to characterize the relationship between changes in permeability and the fractions of the mineral dissolved and deposited. A consistency is found between the calculated longitudinal permeability changes and the quantified distribution of mineral dissolved and deposited along the sample. PMID- 27389613 TI - The development of service user-led recommendations for health and social care services on leaving hospital with memory loss or dementia - the SHARED study. AB - BACKGROUND: Health and social care services are under strain providing care in the community particularly at hospital discharge. Patient and carer experiences can inform and shape services. OBJECTIVE: To develop service user-led recommendations enabling smooth transition for people living with memory loss from acute hospital to community. DESIGN: Lead and co-researchers conducted semi structured interviews with 15 pairs of carers and patients with memory loss at discharge, 6 and 12 weeks post-discharge and one semi-structured interview with health and social care professionals and Admiral Nurses. Framework analysis was guided by co-researchers. Two focus groups of study participants, facilitated by co-researchers, met to shape and finalize recommendations. SETTING AND PARTICIPANTS: Recruitment took place in acute hospitals in two National Health Service (NHS) Trusts in England. Patients were aged 65 and over, with memory loss, an in-patient for at least 1 week returning to the community, who had a carer consenting to be in the study. RESULTS: Poor delivery of services caused considerable stress to some study families living with memory loss. Three key recommendations included a need for a written, mutually agreed discharge plan, a named coordinator of services, and improved domiciliary care services. DISCUSSION AND CONCLUSIONS: Vulnerable patients with memory loss find coming out of hospital after an extended period a stressful experience. The SHARED study contributes to understanding the hospital discharge process through the eyes of the patient and carer living with memory loss and has the potential to contribute to more efficient use of resources and to improving health outcomes in communities. PMID- 27389614 TI - Ebola Surveillance - Guinea, Liberia, and Sierra Leone. AB - Developing a surveillance system during a public health emergency is always challenging but is especially so in countries with limited public health infrastructure. Surveillance for Ebola virus disease (Ebola) in the West African countries heavily affected by Ebola (Guinea, Liberia, and Sierra Leone) faced numerous impediments, including insufficient numbers of trained staff, community reticence to report cases and contacts, limited information technology resources, limited telephone and Internet service, and overwhelming numbers of infected persons. Through the work of CDC and numerous partners, including the countries' ministries of health, the World Health Organization, and other government and nongovernment organizations, functional Ebola surveillance was established and maintained in these countries. CDC staff were heavily involved in implementing case-based surveillance systems, sustaining case surveillance and contact tracing, and interpreting surveillance data. In addition to helping the ministries of health and other partners understand and manage the epidemic, CDC's activities strengthened epidemiologic and data management capacity to improve routine surveillance in the countries affected, even after the Ebola epidemic ended, and enhanced local capacity to respond quickly to future public health emergencies. However, the many obstacles overcome during development of these Ebola surveillance systems highlight the need to have strong public health, surveillance, and information technology infrastructure in place before a public health emergency occurs. Intense, long-term focus on strengthening public health surveillance systems in developing countries, as described in the Global Health Security Agenda, is needed.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27389615 TI - Genomic characterization of a novel poxvirus from a flying fox: evidence for a new genus? AB - The carcass of an Australian little red flying fox (Pteropus scapulatus) which died following entrapment on a fence was submitted to the laboratory for Australian bat lyssavirus exclusion testing, which was negative. During post mortem, multiple nodules were noted on the wing membranes, and therefore degenerate PCR primers targeting the poxvirus DNA polymerase gene were used to screen for poxviruses. The poxvirus PCR screen was positive and sequencing of the PCR product demonstrated very low, but significant, similarity with the DNA polymerase gene from members of the Poxviridae family. Next-generation sequencing of DNA extracted from the lesions returned a contig of 132 353 nucleotides (nt), which was further extended to produce a near full-length viral genome of 133 492 nt. Analysis of the genome revealed it to be AT-rich with inverted terminal repeats of at least 1314 nt and to contain 143 predicted genes. The genome contains a surprisingly large number (29) of genes not found in other poxviruses, one of which appears to be a homologue of the mammalian TNF-related apoptosis inducing ligand (TRAIL) gene. Phylogenetic analysis indicates that the poxvirus described here is not closely related to any other poxvirus isolated from bats or other species, and that it likely should be placed in a new genus. PMID- 27389616 TI - Amino-substituted para-Benzoquinones as Potential Herbicides. AB - Although quinones present a large array of biological activities, a few studies on the herbicidal potential of 2,5-bis(alkyl/arylamino)-1,4-benzoquinones have been reported to date. In this work, starting from benzoquinone, 13 2,5 bis(alkyl/arylamino)-1,4-benzoquinones were prepared in 46 - 93% yield. The products were fully characterized by spectroscopic analyses and their phytotoxicity against Cucumis sativus and Sorghum bicolor seedlings was investigated. At 100 ppm, compounds caused 10 - 88% growth inhibition of the dicotyledonous species, whereas the monocotyledon was less affected. Most compounds exerted little inhibitory effect on a cyanobacterial model strain. However, at 100 MUm, compounds 8 - 10 caused about 50% inhibition of algal growth, and compounds 1 and 2 reduced cell viability in the 1 - 10 MUm range. The ability of benzoquinone derivatives to interfere with the light-driven ferricyanide reduction by isolated spinach chloroplasts was evaluated. Some substances showed a moderate effect as uncouplers, but no relationship was found between this property and their biological activity, indicating that the herbicidal effect is not associated with the inhibition of the photosynthetic electron transport chain. Phytotoxic compounds were not toxic to insects, strengthening the possibility that they may serve as lead for the development of eco-friendly herbicides. PMID- 27389617 TI - Future Papers. PMID- 27389618 TI - [Treatment with immunosuppressive and biologic drugs of pregnant women with systemic rheumatic or autoimmune disease]. AB - Rheumatic and systemic autoimmune diseases occur in women and, to a lesser degree, men of reproductive age. These disorders have to be clinically nonactive before conception, which is usually only possible after anti-inflammatory and immunosuppressive treatment. We must be alert since 50% of pregnancies are unplanned. Physicians should know the embryo-foetal toxicity of these drugs during pregnancy and lactation. This January 2016-updated review allows us to conclude that the majority of immunosuppressives available -anti-TNF inhibitors included- can be used before and during pregnancy, with the exception of cyclophosphamide, methotrexate, mycophenolate and leflunomide. Lactation is permitted with all drugs except methotrexate, leflunomide, mycophenolate and cyclophosphamide. Although data on abatacept, belimumab, rituximab, tocilizumab and anakinra are scant, preliminary reports agree on their safety during pregnancy and, probably, lactation. Cyclophosphamide and sulfasalazine apart, no negative effects on sperm quality, or embryo-foetal anomalies in men treated with immunosuppressives have been described. PMID- 27389620 TI - The response of fish to immunostimulant diets. AB - In order to maintain fish health and to improve performance immunostimulants have been used as dietary additives to improve weight gain, feed efficiency, and/or disease resistance in cultured fish. In aquaculture, non-specific immunostimulants have been widely used probably due to the limited knowledge of the immune response in fish and the ease of their application. Many studies have been carried out to assess the effect of dietary immunostimulants in fish including algal derivatives, herb and plant extract containing diets using a wide range of downstream analytical techniques. Many immunostimulants are based upon tradition and folklore transferred through generations and specific to certain geographical regions rather than known biological properties. However, there are studies in which it is possible to observe a clear and direct dose-dependent stimulatory effect upon the immune system. Other dietary supplements used contain PAMPs (Pathogen Associated Molecular Patterns) as immunostimulants whose recognition depends upon PRR (pathogen recognition receptor) interactions including the TLRs (Toll-like receptor). Despite the growing interest in the use of immunostimulants across the aquaculture industry the underlying mechanisms of ligand recognition, extract composition and activation of the fish immune response remains fragmented. In this review we focus upon the last 15 years of studies addressing the assessment of: (1) plant, herb and algae extracts; and (2) PAMPs, upon non-specific immune parameters of activation and immunostimulant diet efficacy. PMID- 27389619 TI - Construction of high-density genetic linkage map and identification of flowering time QTLs in orchardgrass using SSRs and SLAF-seq. AB - Orchardgrass (Dactylis glomerata L.) is one of the most economically important perennial, cool-season forage species grown and pastured worldwide. High-density genetic linkage mapping is a valuable and effective method for exploring complex quantitative traits. In this study, we developed 447,177 markers based on SLAF seq and used them to perform a comparative genomics analysis. Perennial ryegrass sequences were the most similar (5.02%) to orchardgrass sequences. A high-density linkage map of orchardgrass was constructed using 2,467 SLAF markers and 43 SSRs, which were distributed on seven linkage groups spanning 715.77 cM. The average distance between adjacent markers was 0.37 cM. Based on phenotyping in four environments, 11 potentially significant quantitative trait loci (QTLs) for two target traits-heading date (HD) and flowering time (FT)-were identified and positioned on linkage groups LG1, LG3, and LG5. Significant QTLs explained 8.20 27.00% of the total phenotypic variation, with the LOD ranging from 3.85-12.21. Marker167780 and Marker139469 were associated with FT and HD at the same location (Ya'an) over two different years. The utility of SLAF markers for rapid generation of genetic maps and QTL analysis has been demonstrated for heading date and flowering time in a global forage grass. PMID- 27389621 TI - Improving degradation of paracetamol by integrating gamma radiation and Fenton processes. AB - Degradation of paracetamol (N-(4-hydroxiphenyl)acetamide) in aqueous solution by gamma radiation, gamma radiation/H2O2 and gamma radiation/Fenton processes was studied. Parameters affecting the radiolysis of paracetamol such as radiation dose, initial concentration of pollutant, pH and initial oxidant concentration were investigated. Gamma radiation was performed using a (60)Co source irradiator. Paracetamol degradation and mineralization increased with increasing absorbed radiation dose, but decreased with increasing initial concentration of the drug in aqueous solution. The addition of H2O2 resulted in an increased effect on irradiation-driven paracetamol degradation in comparison with the performance of the irradiation-driven process alone: paracetamol removal increased from 48.9% in the absence of H2O2 to 95.2% for H2O2 concentration of 41.7 mmol/L. However, the best results were obtained with gamma radiation/Fenton process with 100% of the drug removal at 5 kGy, for optimal H2O2 and Fe(2+) concentrations at 13.9 and 2.3 mmol/L, respectively, with a high mineralization of 63.7%. These results suggest gamma radiation/H2O2 and gamma radiation/Fenton processes as promising methods for paracetamol degradation in polluted wastewaters. PMID- 27389622 TI - Blood biomarkers indicate mild neuroaxonal injury and increased amyloid beta production after transient hypoxia during breath-hold diving. AB - OBJECTIVE: To determine whether transient hypoxia during breath-hold diving causes neuronal damage or dysfunction or alters amyloid metabolism as measured by certain blood biomarkers. DESIGN: Sixteen divers competing in the national Swedish championship in breath-hold diving and five age-matched healthy control subjects were included. Blood samples were collected at baseline and over a course of 3 days where the divers competed in static apnea (STA), dynamic apnea without fins (DYN1) and dynamic apnea with fins (DYN2). MAIN OUTCOMES: Biomarkers reflecting brain injury and amyloid metabolism were analysed in serum (S-100beta, NFL) and plasma (T-tau, Abeta42) using immunochemical methods. RESULTS: Compared to divers' baseline, Abeta42 increased after the first event of static apnea (p = 0.0006). T-tau increased (p = 0.001) in STA vs baseline and decreased after one of the dynamic events, DYN2 (p = 0.03). Further, T-tau correlated with the length of the apneic time during STA (rho = 0.7226, p = 0.004) and during DYN1 (rho = 0.66, p = 0.01). CONCLUSION: The findings suggest that transient hypoxia may acutely increase the levels of Abeta42 and T-tau in plasma of healthy adults, further supporting that general hypoxia may cause mild neuronal dysfunction or damage and stimulate Abeta production. PMID- 27389624 TI - Research Registries: A Tool to Advance Understanding of Rare Neuro-Ophthalmic Diseases. AB - BACKGROUND: Medical research registries (MRR) are organized systems used to collect, store, and analyze patient information. They are important tools for medical research with particular application to the study of rare diseases, including those seen in neuro-ophthalmic practice. EVIDENCE ACQUISITION: Evidence for this review was gathered from the writers' experiences creating a comprehensive neuro-ophthalmology registry and review of the literature. RESULTS: MRR are typically observational and prospective databases of de-identified patient information. The structure is flexible and can accommodate a focus on specific diseases or treatments, surveillance of patient populations, physician quality improvement, or recruitment for future studies. They are particularly useful for the study of rare diseases. They can be integrated into the hierarchy of medical research at many levels provided their construction is well organized and they have several key characteristics including an easily manipulated database, comprehensive information on carefully selected patients, and comply with human subjects regulations. MRR pertinent to neuro-ophthalmology include the University of Illinois at Chicago neuro-ophthalmology registry, Susac Syndrome Registry, Intracranial Hypertension Registry, and larger-scale patient outcome registries being developed by professional societies. CONCLUSION: MRR have a variety of forms and applications. With careful planning and clear goals, they are flexible and powerful research tools that can support multiple different study designs, and this can provide the potential to advance understanding and care of neuro-ophthalmic diseases. PMID- 27389623 TI - Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination. AB - Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl(-) concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours. PMID- 27389625 TI - A Nonarteritic Anterior Ischemic Optic Neuropathy Clinical Trial: An Industry and NORDIC Collaboration. PMID- 27389626 TI - Can Corneal Biomechanical Properties Give Clues About Elasticity of Optic Nerve Scleral Component in Nonarteritic Anterior Ischemic Optic Neuropathy? AB - OBJECTIVE: To investigate corneal biomechanical properties among individuals with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) compared to healthy gender- and age-matched subjects. METHODS: The study subjects were separated into 2 groups: 66 eyes of 33 patients with unilateral NAION (study group) and 33 eyes of 33 healthy individuals (control group). Reichert ocular response analyzer (Reichert Ophthalmic Instruments) was used to assess corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure values. Also, central corneal thickness was measured using Scheimpflug camera combined with a Placido disc corneal topographer (Sirius; Costruzioni Strumenti Oftalmici). RESULTS: Mean CH and median CRF values were significantly lower in the affected eyes (8.8 +/- 1.8 mm Hg, 9.4 mm Hg, respectively) and contralateral unaffected eyes (9.1 +/- 1.6 mm Hg, 9.8 mm Hg, respectively) of NAION patients than those in the control group (9.9 +/- 1.3 mm Hg, 10.4 mm Hg, respectively; all P < 0.017). Mean IOPcc was significantly higher in the affected eyes of NAION patients (19.2 +/- 3.5 mm Hg) than in the eyes of control group (17.1 +/- 3.6 mm Hg; P = 0.002). CONCLUSIONS: CH and CRF are significantly reduced in patients with NAION, possibly indirectly reflecting structural weakness in the lamina cribrosa. PMID- 27389627 TI - Predicting bifurcation angle effect on blood flow in the microvasculature. AB - Since blood viscosity is a basic parameter for understanding hemodynamics in human physiology, great amount of research has been done in order to accurately predict this highly non-Newtonian flow property. However, previous works lacked in consideration of hemodynamic changes induced by heterogeneous vessel networks. In this paper, the effect of bifurcation on hemodynamics in a microvasculature is quantitatively predicted. The flow resistance in a single bifurcation microvessel was calculated by combining a new simple mathematical model with 3-dimensional flow simulation for varying bifurcation angles under physiological flow conditions. Interestingly, the results indicate that flow resistance induced by vessel bifurcation holds a constant value of approximately 0.44 over the whole single bifurcation model below diameter of 60MUm regardless of geometric parameters including bifurcation angle. Flow solutions computed from this new model showed substantial decrement in flow velocity relative to other mathematical models, which do not include vessel bifurcation effects, while pressure remained the same. Furthermore, when applying the bifurcation angle effect to the entire microvascular network, the simulation results gave better agreements with recent in vivo experimental measurements. This finding suggests a new paradigm in microvascular blood flow properties, that vessel bifurcation itself, regardless of its angle, holds considerable influence on blood viscosity, and this phenomenon will help to develop new predictive tools in microvascular research. PMID- 27389628 TI - Diet, lipids, and cardiovascular disease. AB - PURPOSE OF REVIEW: Modulation of diet is the primary lifestyle approach for reducing cardiovascular disease (CVD) risk, with a major focus of current guidelines being to lower LDL cholesterol by reducing intake of saturated fatty acids. However, dietary effects on lipid-related CVD risk factors extend beyond LDL cholesterol, with growing emphasis on the prevention and management of atherogenic dyslipidemia, which includes elevated triglyceride, small dense LDL, and reduced HDL cholesterol, and which is associated with excess adiposity and insulin resistance. We here review recent studies of dietary macronutrient effects on CVD risk that may act through effects on plasma lipid and lipoprotein metabolism. RECENT FINDINGS: Effects of reducing saturated fatty acids on CVD risk have been evaluated both in terms of the replacement macronutrient(s) and the food and dietary context in which the macronutrients are consumed. Although weight loss remains the most important goal for reducing cardiometabolic risk among overweight and obese individuals, a variety of lines of evidence support limitation of added sugars and processed starches for improving features of atherogenic dyslipidemia. SUMMARY: Increasing understanding of the complexity of nutrient-disease relationships has shifted the framework for CVD prevention from a focus on macronutrient content of diets to foods and dietary patterns. PMID- 27389630 TI - Vaccine strategies for lowering LDL by immunization against proprotein convertase subtilisin/kexin type 9. AB - PURPOSE OF REVIEW: mAbs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have the potential to become groundbreaking therapies for the treatment of hypercholesterolemia. However, one major drawback of mAb-based therapy for a chronic condition like dyslipidemia is its relatively high cost. This review summarizes two recent studies describing novel vaccine approaches for lowering LDL-cholesterol by active immunization against PCSK9. RECENT FINDINGS: PCSK9 is a plasma protein secreted by the liver that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the LDL receptor. Two PCSK9 inhibitory mAbs (evolocumab and alirocumab) have recently been approved by the Food and Drug Administration and a third mAb (bococizumab) is in late stage clinical trials. Treatment with PCSK9 mAbs, in combination with statins, reduces LDL-cholesterol levels by as much as 40-60%. As an alternative to mAbs, there have been two recent studies describing the development of vaccines that target PCSK9. These studies have shown that PCSK9 vaccines can effectively induce high titer antibody responses that reduce proatherogenic lipoproteins in animal models. SUMMARY: A PCSK9 vaccine-based approach could serve as a more widely applicable and a more cost-effective approach than mAb therapy for controlling hypercholesteremia and associated cardiovascular disease. PMID- 27389631 TI - Should apolipoprotein B replace LDL cholesterol as therapeutic targets are lowered? AB - PURPOSE OF REVIEW: The success of LDL cholesterol (LDL-C) as a predictor of atherosclerotic cardiovascular disease and a therapeutic target is indisputable. Apolipoprotein B (apoB) is a more contemporary and physiologically relevant measure of atherogenic lipoproteins. This report summarizes recent comparisons of apoB and LDL-C as biomarkers of cardiovascular risk. RECENT FINDINGS: Multiple recent reports have found that LDL-C methods perform poorly at low concentrations (<70 mg/dl). Several meta-analyses from randomized controlled trials and large prospective observational studies have found that apoB and LDL-C provide equivalent information on risk of cardiovascular disease. More innovative analyses have asserted that apoB is a superior indicator of actual risk when apoB and LDL-C disagree. SUMMARY: ApoB is more analytically robust and standardized biomarker than LDL-C. Large population studies have found that apoB is at worst clinically equivalent to LDL-C and likely superior when disagreement exists. Realistically, many obstacles prevent the wide spread adoption of apoB and for now providers and their patients must weigh the costs and benefits of apoB. PMID- 27389629 TI - Cardiovascular diseases in mega-countries: the challenges of the nutrition, physical activity and epidemiologic transitions, and the double burden of disease. AB - PURPOSE OF REVIEW: There are today 11 mega-countries with more than 100 million inhabitants. Together these countries represent more than 60% of the world's population. All are facing noncommunicable chronic disease (NCD) epidemic where high cholesterol, obesity, diabetes, and cardiovascular diseases are becoming the main public health concerns. Most of these countries are facing the double burden of malnutrition where undernutrition and obesity coexist, increasing the complexity for policy design and implementation. The purpose of this study is to describe diverse sociodemographic characteristics of these countries and the challenges for prevention and control in the context of the nutrition transition. RECENT FINDINGS: Mega-countries are mostly low or middle-income and are facing important epidemiologic, nutrition, and physical activity transitions because of changes in food systems and unhealthy lifestyles. NCDs are responsible of two thirds of the 57 million global deaths annually. Approximately, 80% of these are in low and middle-income countries. Only developed countries have been able to reduce mortality rates attributable to recognized risk factors for NCDs, in particular high cholesterol and blood pressure. SUMMARY: Mega-countries share common characteristics such as complex bureaucracies, internal ethnic, cultural and socioeconomic heterogeneity, and complexities to implement effective health promotion and education policies across population. Priorities for action must be identified and successful lessons and experiences should be carefully analyzed and replicated. PMID- 27389632 TI - Diagnostic scoring for familial hypercholesterolaemia in practice. AB - PURPOSE OF REVIEW: Diagnostic scoring for familial hypercholesterolaemia (FH) can be used either to screen for possible FH or guide the selection of patients for genetic (DNA) testing. We review the published diagnostic criteria and discuss the options for future development. RECENT FINDINGS: Scoring systems have been developed internationally based on lipid values and various combinations of clinical signs and cardiovascular history. The predictive value varies according to the test population, be it lipid clinic referrals, general population, or relatives of patients with FH. Also, there is increasing recognition of genetic heterogeneity in FH so that criteria are of differing predictive value depending on the genetic variant of FH. SUMMARY: These clinical scoring systems are increasingly used to guide selection of patients for FH genetic testing but no single approach has yet emerged as the system of choice. Further refinement of these scoring tools using more sophisticated calculators are superseding the more manual approaches. These are well suited to web-based tools or smartphone applications. PMID- 27389633 TI - Corrigendum: Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing. PMID- 27389634 TI - Right atrial mass with a pulmonary embolism. PMID- 27389635 TI - Proteomics of Plasmodium vivax malaria: new insights, progress and potential. AB - INTRODUCTION: Plasmodium vivax has accounted for an enormous share of the global malaria burden in recent years, along with Plasmodium falciparum. The wide distribution of P. vivax and recent evidences of severe and complicated vivax malaria across several endemic regions of the world suggest that this disease may have been more overlooked than benign. While P. falciparum has been extensively studied, P. vivax has received limited research attention owing to its complex nature and absence of a continuous culture system. AREAS COVERED: This review briefly describes the epidemiology of vivax malaria, analyzes challenges towards effective control and summarizes major insights provided by genomics and transcriptomics research in the area. Subsequently, the review provides a detailed description of the applications of proteomics in vivax malaria research, focusing on both host responses and parasite proteomics studies to understand P. vivax biology. Expert commentary: In recent years, proteomics technologies are being used effectively to understand P. vivax biology and the underlying pathogenesis. Technological advances in mass spectrometry configurations, multiomics investigations and emerging strategies such as targeted proteomics may also immensely aid in studying disease severity, improving existing diagnosis and identifying new drug and vaccine targets. PMID- 27389637 TI - A smoking cessation programme for current and recent ex-smokers following diagnosis of a potentially curable cancer. AB - BACKGROUND: Cancer patients who quit smoking have improved survival rates. The time of diagnosis provides a 'teachable moment' when healthcare providers can offer smoking-cessation treatment. AIMS: To assess the impact on quit rates of a tailored smoking-cessation intervention for patients diagnosed with a potentially curable cancer. METHODS: A prospective, one-arm cohort study of current smokers and recent quitters (<30 days) who had commenced treatment for a potentially curable cancer was performed. Intervention involved an initial motivational interview, regular follow up and pharmacotherapy when appropriate. Quit rates were measured at 1, 3, 6 and 12 months by self-reported abstinence and biochemical confirmation. The primary end point was prolonged abstinence at 12 months. Changes in quality of life parameters and distress were also assessed. RESULTS: Seventy-one patients were recruited, with a median age of 56 years. Forty-one patients (58%) had a smoking-related cancer. The prolonged abstinence rate at 12 months was 24% (95% confidence interval 14-36%). Factors associated with successful quitting included being in the preparation or action phase of readiness to change at study entry (P = 0.012) and having complications of treatment requiring hospitalisation (P = 0.024). Between baseline and 12 months, quitters reported improvement in self-control (P < 0.001) and reduced levels of distress (P = 0.03) compared to non-quitters. CONCLUSION: Patients who continue to smoke after being diagnosed with cancer require intensive support to quit. An individualised behavioural and pharmacological intervention can be successful in helping patients quit smoking, with quality of life improvements seen amongst successful quitters. Population measures to stop people starting smoking remain essential. PMID- 27389638 TI - Sensitivity and resolution of two-dimensional NMR diffusion-relaxation measurements. AB - The performance of 2D NMR diffusion-relaxation measurements for fluid typing applications is analyzed. In particular, we delineate the region in the diffusion - relaxation plane that can be determined with a given gradient strength and homogeneity, and compare the performance of the single and double echo encoding with the stimulated echo diffusion encoding. We show that the diffusion editing based approach is able to determine the diffusion coefficient only if the relaxation time T2 exceeds a cutoff value T2,cutoff, that scales like T2,cutoff?g(-2/3)D(-1/3). For stimulated echo encoding, the optimal diffusion encoding times (Td and delta), that provide the best diffusion sensitivity, rely only on the T1/T2 ratios and not on the diffusion coefficients of the fluids or the applied gradient strengths. Irrespective of T1, for high enough gradients (i.e. when gamma(2)g(2)DT2(3)>10(2)), the Hahn echo based encoding is superior to encoding based on the stimulated echo. For weaker gradients, the stimulated echo is superior only if the T1/T2 ratio is much larger than 1. For single component systems, the diffusion sensitivity is not adversely impacted by the uniformity of the gradients and the diffusion distributions can be well measured. The presence of non-uniform gradients can affect the determination of the diffusion distributions when you have two fluids of comparable T2. In such situations the effective single component diffusion coefficient is always closer to the geometric mean diffusion coefficient of the two fluids. PMID- 27389636 TI - Characterization of two PEBP genes, SrFT and SrMFT, in thermogenic skunk cabbage (Symplocarpus renifolius). AB - Floral thermogenesis has been found in dozens of primitive seed plants and the reproductive organs in these plants produce heat during anthesis. Thus, characterization of the molecular mechanisms underlying flowering is required to fully understand the role of thermogenesis, but this aspect of thermogenic plant development is largely unknown. In this study, extensive database searches and cloning experiments suggest that thermogenic skunk cabbage (Symplocarpus renifolius), which is a member of the family Araceae, possesses two genes encoding phosphatidyl ethanolamine-binding proteins (PEBP), FLOWERING LOCUS T (SrFT) and MOTHER OF FT AND TFL1 (SrMFT). Functional analyses of SrFT and SrMFT in Arabidopsis indicate that SrFT promotes flowering, whereas SrMFT does not. In S. renifolius, the stage- and tissue-specific expression of SrFT was more evident than that of SrMFT. SrFT was highly expressed in flowers and leaves and was mainly localized in fibrovascular tissues. In addition, microarray analysis revealed that, within floral tissues, SrFT was co-regulated with the genes associated with cellular respiration and mitochondrial function, including ALTERNATIVE OXIDASE gene proposed to play a major role in floral thermogenesis. Taken together, these data suggest that, among the PEBP genes, SrFT plays a role in flowering and floral development in the thermogenic skunk cabbage. PMID- 27389639 TI - Improving accuracy in DOSY and diffusion measurements using triaxial field gradients. AB - NMR measurements of diffusion in solution, whether primarily quantitative, or, (as in DOSY, Diffusion-Ordered Spectroscopy) qualitative, can be particularly demanding. Here we show how the use of appropriate transverse (x, y) pulsed field gradients, orthogonal to the more usual z axis pulsed field gradient applied along the long axis of the sample, can greatly reduce two important sources of systematic error in diffusion experiments. These are the extra signal attenuation caused by sample convection, and gradient-dependent signal phase shifts caused by the magnetic field and field-frequency lock disturbances generated by field gradient pulses. PMID- 27389640 TI - Measurement of J-couplings between chemically equivalent nuclei using off resonance decoupling. AB - The method of measuring J-couplings between chemically equivalent nuclei in isotopically/magnetically non-equivalent environment, based on off-resonance decoupling, is described. The approach uses intensities, rather than frequencies of the spectral peaks and, therefore, the accuracy of measurement is not limited by spectral resolution. PMID- 27389641 TI - Surgical vs Nonsurgical Treatment Modalities for T3 Glottic Squamous Cell Carcinoma. AB - Importance: Further investigation is needed in the outcomes of currently available treatment for T3 glottic squamous cell carcinoma (SCC), a unique type of laryngeal cancer. Objective: To compare overall survival (OS) and functional outcomes among patients with T3 glottic SCC receiving nonsurgical and surgical management. Design, Setting, and Participants: This secondary analysis used data from the Surveillance, Epidemiology, and End Results (SEER) registry and Medicare databases. All patients with T3 glottic SCC who received a diagnosis from January 1, 1992, to December 31, 2010, were included. Data were analyzed from April 2014 to August 2015. Interventions: Surgery with or without adjuvant radiotherapy and/or chemotherapy. Main Outcomes and Measures: Five-year OS and functional outcomes. Results: Among the 487 patients identified with T3 glottic SCC (418 men [85.8%]; 69 women [14.2%]; median age, 74.3 [interquartile range, 70.4-80.6] years), the 5-year OS for nonsurgical management, surgery alone, and surgery plus adjuvant treatment were 36% (95% CI, 30%-42%), 41% (95% CI, 30%-53%), and 41% (95% CI, 32%-51%), respectively. Multivariable analyses revealed an adjusted hazard ratio for OS of 0.68 (95% CI, 0.49-0.94) for patients receiving surgery alone vs nonsurgical management and 0.75 (95% CI, 0.57-0.98) for patients receiving surgery plus adjuvant treatment vs nonsurgical management. Gastrostomy tube dependence was highest in patients receiving surgery plus adjuvant treatment (30 of 98 patients [30.6%]). Tracheostomy dependence was highest in patients receiving chemoradiotherapy (34 of 92 patients [37.0%]). Conclusions and Relevance: Overall survival showed a statistically significant and clinically meaningful improvement in patients with T3 glottic SCC who underwent surgery compared with a nonsurgical treatment. Furthermore, the data suggest that adjuvant and nonsurgical treatment result in a dysfunctional larynx; however, this association needs further study. PMID- 27389642 TI - Detecting Topological Defect Dark Matter Using Coherent Laser Ranging System. AB - In the last few decades, optical frequency combs with high intensity, broad optical bandwidth, and directly traceable discrete wavelengths have triggered rapid developments in distance metrology. However, optical frequency combs to date have been limited to determine the absolute distance to an object (such as satellite missions). We propose a scheme for the detection of topological defect dark matter using a coherent laser ranging system composed of dual-combs and an optical clock via nongravitational signatures. The dark matter field, which comprises a defect, may interact with standard model particles, including quarks and photons, resulting in the alteration of their masses. Thus, a topological defect may function as a dielectric material with a distinctive frequency-depend index of refraction, which would cause the time delay of a periodic extraterrestrial or terrestrial light. When a topological defect passes through the Earth, the optical path of long-distance vacuum path is altered, this change in optical path can be detected through the coherent laser ranging system. Compared to continuous wavelength(cw) laser interferometry methods, dual-comb interferometry in our scheme excludes systematic misjudgement by measuring the absolute optical path length. PMID- 27389645 TI - Thermostabilization by Proline Substitution in an Alkaline, Liquefying alpha Amylase from Bacillus sp. Strain KSM-1378. AB - alpha-Amylase (LAMY) from alkaliphilic Bacillus sp. strain KSM-1378 is a novel semi-alkaline enzyme which has 5-fold higher specific activity than that of a Bacillus licheniformis enzyme. The Arg124 in LAMY was replaced with proline by site-directed mutagenesis to increase thermostability of the enzyme. The wild type and engineered LAMYs were very similar with respect to specific activity, kinetic values, pH-activity curve, and degree of inhibition by chelating reagents. Thermostability and structure stiffness of LAMYs as measured by fluorescence were increased by the proline substitution. The change of Arg124 to proline is assumed to stabilize the loop region involving aminio acid residues from 122 to 134. This is the first report that thermostability of an alpha amylase is improved by proline substitution. PMID- 27389646 TI - Crystallization and Properties of NAD-Dependent D-Sorbitol Dehydrogenase from Gluconobacter suboxydans IFO 3257. AB - NAD-dependent D-sorbitol dehydrogenase (EC 1.1.1.14) was crystallized from the cytosolic fraction of Gluconobacter suboxydans IFO 3257. This is the first example of the enzyme crystallized from acetic acid bacteria. The enzyme catalyzed oxidoreduction between D-sorbitol and D-fructose in the presence of NAD or NADH. The crystalline enzyme showed a single sedimentation peak in analytical ultracentrifugation, giving an apparent sedimentation constant of 5.1s. Gel filtration on a Sephadex G-200 column gave the molecular mass of 98 kDa for the enzyme, which dissociated into 26-kDa subunits on SDS-PAGE, indicating that the enzyme is composed of four identical subunits. Oxidation of D-sorbitol to D fructose and xylitol to D-xylulose predominated in the presence of NAD at the optimum pH of 9.5-10.0. Reductions of D-fructose to D-sorbitol and D-xylulose to xylitol were also observed in the presence of NADH with the optimum pH around 6.0. The relative rate of D-fructose reduction was about one-fourth of that of D sorbitol oxidation. NADP and NADPH were inert for the both reactions. Since the reation rate in D-sorbitol oxidation predominated over D-fructose reduction at some alkaline pH, the enzyme could be available for direct enzymatic measurement of D-sorbitol. Even in the presence of a large excess of D-glucose and other substances, reduction of NAD to NADH was highly specific and stoichiometric to the D-sorbitol oxidized. PMID- 27389643 TI - Age and sex differences in oxytocin and vasopressin V1a receptor binding densities in the rat brain: focus on the social decision-making network. AB - Oxytocin (OT) and vasopressin (AVP) regulate various social behaviors via activation of the OT receptor (OTR) and the AVP V1a receptor (V1aR) in the brain. Social behavior often differs across development and between the sexes, yet our understanding of age and sex differences in brain OTR and V1aR binding remains incomplete. Here, we provide an extensive analysis of OTR and V1aR binding density throughout the brain in juvenile and adult male and female rats, with a focus on regions within the social decision-making network. OTR and V1aR binding density were higher in juveniles than in adults in regions associated with reward and socio-spatial memory and higher in adults than in juveniles in key regions of the social decision-making network and in cortical regions. We discuss possible implications of these shifts in OTR and V1aR binding density for the age-specific regulation of social behavior. Furthermore, sex differences in OTR and V1aR binding density were less numerous than age differences. The direction of these sex differences was region-specific for OTR but consistently higher in females than in males for V1aR. Finally, almost all sex differences in OTR and V1aR binding density were already present in juveniles and occurred in regions with denser binding in adults compared to juveniles. Possible implications of these sex differences for the sex-specific regulation of behavior, as well potential underlying mechanisms, are discussed. Overall, these findings provide an important framework for testing age- and sex-specific roles of OTR and V1aR in the regulation of social behavior. PMID- 27389647 TI - Stereoselective Synthesis of Optically Active Methylene Lactone, Key Intermediate for the Synthesis of 1,2-Oxidized Furofuran Lignan, from L-Glutamic Acid. AB - (4R)-[(1S)-1-[(tert-Butyldimethylsilyl)oxy]-1-(2-methoxy-4,5 methylenedioxyphenyl)methyl]-3-methylenedihydro-2(3H)-furanone and (4R)-[(1R)-1 [(tert-butyldimethylsilyl)oxy]-1-(2-methoxy-4,5-methylenedioxyphenyl)methyl]-3 methylenedihydro-2(3H)-furanone, which are key intermediates for the synthesis of 1,2-oxidized furofuran lignan, were each stereoselectively synthesized from L glutamic acid. PMID- 27389648 TI - Occurrence and Characterization of 2-Hydroxy-1,4-benzoxazin-3-one and Indole Hydroxylases in Juvenile Wheat. AB - Cyclic hydroxamic acids, 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) and its 7 methoxy analogue (DIMBOA), occur transiently in high amounts in wheat and maize during the juvenile, non-autotrophic stage of growth. To elucidate the biosynthetic enzymes operating for the transient production of these compounds, we examined the hydroxylating activities for 2-hydroxy-1,4-benzoxazin-3-one (HBOA), the immediate precursor of DIBOA, and indole, the first intermediate of the biosynthetic pathway that branches off from the tryptophan pathway, by using microsomes prepared from wheat seedlings. Both hydroxylases occurred soon after germination, reached a maximum 48 h after germination, and decreased to finally disappear as the plants grew into the autotrophic growth stage. The mode of appearance and disappearance similar to that of hydroxamic acids, suggesting that elevated expression of the whole set of enzymes involved in the biosynthesis after indole was responsible for the transient occurrence of hydroxamic acids. The hydroxylating activity was also observed for 1,4-benzoxazin-3-one, a putative precursor of HBOA, but to significantly less extent than that for HBOA and indole. PMID- 27389649 TI - Purification and Properties of Chitinase from Arthrobacter sp. NHB-10. AB - A chitinase was purified from the culture filtrate of nigeran-degrading Arthrobacter sp. NHB-10 by precipitation with ammonium sulfate and column chromatographies on DEAE-Sephadex A-50 and Superose 12. The final preparation was homogenous in polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme was 30,000 and its isoelectric point was 6.8. The optimum pH and temperature for the enzyme activity were 5.0 and 45 degrees C, respectively. The enzyme was stable from pH 3 to 7 and up to 55 degrees C. The enzyme activity was inhibited by Hg(2+) and p-chloromercuribenzoic acid. Two internal amino acid sequences of the enzyme were AGPQLLTGYY and IGGVMT. PMID- 27389650 TI - Coenzyme Activity of NAD Analogs for 3-Isopropylmalate Dehydrogenase from Thermus thermophilus HB8. AB - In order to elucidate the enzyme-substrate-cofactor interaction in 3 isopropylmalate dehydrogenase, the coenzyme activity of NAD analogs which have a 3-substituted pyridine ring was examined. Analogs 3-5 showed diminished k cat values compared with those of NAD(+), whereas thiocarboxamide 2 was almost as equally active as NAD(+). This suggests that the NH2 functionality of NAD(+) is more important for the catalysis of IPMDH than a carbonyl group. PMID- 27389644 TI - Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours. AB - A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is 'synthetic' v. what is 'natural,' shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour. PMID- 27389651 TI - Inhibition of Plant Transformation by Phytolaccoside B from Phytolacca americana Callus. AB - The newly established GUS expression bioassay on the callus extracts of 22 species of plants revealed that the methanol extract of Phytolacca americana callus had the most potent inhibitory activity against agrobacterial plant transformation. A triterpene glycoside phytolaccoside B was isolated from the extract as a genuine plant transformation inhibitor having neither antiagrobacterial nor phytotoxic activity. This compound is promising for use as a biochemical probe for studies on the plant transformation mechanism. PMID- 27389652 TI - A Novel Rearranged Taxoid from Needles of the Japanese Yew, Taxus cuspidata Sieb. et Zucc. AB - Eleven taxoids were isolated from needles of the Japanese yew, Taxus cuspidata Sieb. et Zucc., one of them being a new compound whose structure was established as 5alpha-cinnamoyl-9alpha,10beta,13alpha-triacetoxy-11(15->1)abeotaxa-4(20),11 dien-15-ol (7-deactoxytaxuspine J) on the basis of a spectroscopic analysis. Its relative stereochemistry is proposed from the results of a NOESY experiment. PMID- 27389653 TI - Preparative-scale Enzyme-catalyzed Synthesis of (R)-alpha-Fluorophenylacetic Acid. AB - A preparative-scale asymmetric synthesis of (R)-alpha-fluorophenylacetic acid, a useful chiral derivatizing reagent, is described. Starting from ethyl alpha bromophenylacetate, alpha-fluorophenylmalonic acid dipotassium salt was prepared in three steps (54% yield), including nucleophilic substitution by the fluoride ion as the keystep. Both the purified form and crude preparation of arylmalonate decarboxylase in E. coli worked well on this substrate, and (R)-alpha flurophenylacetic acid (>99% e.e.) was prepared in a quantitative yield. PMID- 27389654 TI - Isolation of (-)-14-O-Malonylindolactam-V as a Possible Precursor of (-) Indolactam-V and (-)-14-O-Acetylindolactam-V from Streptomyces blastmyceticum. AB - (-)-Indolactam-V (1) has the fundamental structure of potent tumor-promoting teleocidins. A new teleocidin-related metabolite, (-)-14-O-malonylindolactam-V (2), was isolated from the culture broth of Streptomyces blastmyceticum NA34-17 which produced a large quantity of 1 along with a small amount of (-)-14-O acetylindolactam-V (3). Heat treatment of 2 in methanol readily produced 1 and 3, suggesting that S. blastmyceticum NA34-17 excreted 1 as a malonic acid conjugate to accumulate 1 and 3 in the culture broth during cultivation. PMID- 27389655 TI - Mammographic density is the main correlate of tumors detected on ultrasound but not on mammography. AB - Although mammography screening programs do not include ultrasound examinations, some diagnostic units do provide women with both mammography and ultrasonography. This article is concerned with estimating the risk of a breast cancer patient diagnosed in a hospital-based mammography unit having a tumor that is visible on ultrasound but not on mammography. A total of 1,399 women with invasive breast cancer from a hospital-based diagnostic mammography unit were included in this retrospective study. For inclusion, mammograms from the time of the primary diagnosis had to be available for computer-assisted assessment of percentage mammographic density (PMD), as well as Breast Imaging Reporting and Data System (BIRADS) assessment of mammography. In addition, ultrasound findings were available for the complete cohort as part of routine diagnostic procedures, regardless of any patient or imaging characteristics. Logistic regression analyses were conducted to identify predictors of mammography failure, defined as BIRADS assessment 1 or 2. The probability that the visibility of a tumor might be masked at diagnosis was estimated using a regression model with the identified predictors. Tumors were only visible on ultrasound in 107 cases (7.6%). PMD was the strongest predictor for mammography failure, but age, body mass index and previous breast surgery also influenced the risk, independently of the PMD. Risk probabilities ranged from 1% for a defined low-risk group up to 40% for a high risk group. These findings might help identify women who should be offered ultrasound examinations in addition to mammography. PMID- 27389656 TI - Site of infection and mortality in patients with severe sepsis or septic shock. A cohort study of patients admitted to a Danish general intensive care unit. AB - BACKGROUND: The search for the site of infection has high priority in patients with severe sepsis and septic shock. However, it is questionable whether mortality is associated with the specific site of infection in patients admitted to an intensive care unit (ICU). Therefore, the 30-day and 90-day mortalities in ICU patients admitted with suspected or confirmed community-acquired infection were studied. METHODS: A retrospective cohort study was conducted, including all adult patients admitted to a multi-specialty tertiary ICU with severe sepsis or septic shock from November 2008 to October 2010. The site of infection was classified according to criteria set for healthcare associated infections and infections in the acute care setting by Centers for Disease Control and Prevention (CDC). Kaplan-Meier curves and Poisson regression analysis were used to evaluate the association between site of infection and 30- and 90-day all cause mortality, adjusting for age, sex and comorbidities. RESULTS: Three hundred and eighty-eight patients were included. One or more comorbidities were present in 76% of patients. Across all sites of infection, there were more patients with septic shock than patients with severe sepsis. The most frequent site of infection was pneumonia, followed by gastrointestinal infection. Urinary tract infection was found to be an independent predictor of mortality among septic ICU patients when adjusting for sex, age and comorbidities. CONCLUSIONS: The results suggest that identification of correct site of infection is important in the management of severe sepsis and septic shock. PMID- 27389658 TI - Sign inversion of surface stress-charge response of bulk nanoporous nickel actuators with different surface states. AB - The surface stress-charge coefficient, zeta, is a fundamental material parameter and reflects the response of surface stress to the change of superficial charge. The sign and the quantity of zeta play a crucial role in electrochemically induced actuation of nanostructured metals. Here, for the first time, we address the electrochemical actuation and the associated stress-charge coefficients of bulk nanoporous nickel (np-Ni) in both strongly (NaOH) and weakly (NaF) adsorbed electrolytes. The results reveal a normal negative value of zeta for the np-Ni with the clean surface, and unusual positive values of zeta for the oxide-covered surface. Interestingly, the oxidized np-Ni cannot recover the conventional negative value of zeta even in the cathodic potential window. Moreover, the reversible strain amplitude and the involved charge are quite different in distinct potential windows (the same electrolyte) or in different electrolytes (strongly or weakly adsorbed). In addition, density functional theory (DFT) calculations have been performed to understand the electrochemical actuation behaviors of the np-Ni with different surface states. In some aspects, the scenario of the np-Ni indeed differs from that of nanoporous noble metals like Au or Pt. Our findings provide useful information on understanding the electrochemical actuation of nanostructured metals, and novel actuators or sensors could be developed based upon earth-abundant metals like Ni, Co, and so forth. PMID- 27389657 TI - A Memory of Majorana Modes through Quantum Quench. AB - We study the sudden quench of a one-dimensional p-wave superconductor through its topological signature in the entanglement spectrum. We show that the long-time evolution of the system and its topological characterization depend on a pseudomagnetic field Reff(k). Furthermore, Reff(k) connects both the initial and the final Hamiltonians, hence exhibiting a memory effect. In particular, we explore the robustness of the Majorana zero-mode and identify the parameter space in which the Majorana zero-mode can revive in the infinite-time limit. PMID- 27389659 TI - Novel growth method of carbon nanotubes using catalyst-support layer developed by alumina grit blasting. AB - We propose an efficient method of growing carbon nanotube (CNT) arrays on a variety of metals, alloys, and carbon materials using chemical vapor deposition (CVD) assisted by a simple surface treatment of the materials. The main feature of this method is the application of grit blasting with fine alumina particles to the development of a catalyst-support layer required for the growth of CNTs on various conductive materials, including ultra-hard metals such as tungsten. Auger electron spectroscopy shows that grit blasting can form a non-continuous layer where alumina nanoparticles are embedded as residues in the blasting media left on the treated surfaces. This work reveals that such a non-continuous alumina layer can behave as the catalyst-support layer, which is generally prepared by sputter or a vacuum evaporation coating process that considerably restricts the practical applications of CNTs. We have attempted to grow CNTs on grit-blasted substrates of eighteen conventionally used conductive materials using CVD together with a floating iron catalyst. The proposed method was successful in growing multi-walled CNT arrays on the grit-blasted surfaces of all the examined materials, demonstrating its versatility. Furthermore, we found that the group IV metal oxide films thermally grown on the as-received substrates can support the catalytic activity of iron nanoparticles in the CVD process just as well as the alumina film developed by grit blasting. Spectral emissivity of the CNT arrays in the visible and infrared wavelength ranges has been determined to assess the applicability of the CNT arrays as a black coating media. PMID- 27389664 TI - Systematic review for pre-market risk assessment. PMID- 27389666 TI - Therapeutic alliance, empathy, and genuineness in individual adult psychotherapy: A meta-analytic review. AB - OBJECTIVE: Alliance, empathy, and genuineness are each integral parts of the therapeutic relationship. No previous meta-analysis has explored the extent to which therapist empathy and genuineness contribute to the therapeutic alliance. METHOD: In this meta-analysis, a multifaceted search strategy yielded 53 studies. Forty studies reported alliance/empathy relationships, eight studies reported alliance/genuineness relationships, and five studies reported both. RESULTS: Random effects meta-analyses revealed that therapeutic alliance was significantly related to perceptions of therapist empathy with a mean r = 0.50 (95% CI = 0.42, 0.57). Therapeutic alliance was also significantly related to perceptions of therapist genuineness with a mean r = 0.59 (95% CI = 0.45, 0.71). Tests of publication bias indicated a low likelihood of publication bias affecting the strength and direction of the results. Potential moderating variables were explored, including rater perspective, measure of therapeutic relationship variables, and client race/ethnicity. CONCLUSIONS: Therapeutic alliance has a moderate relationship with perceptions of therapist empathy and genuineness. Of note, there may be reason to believe that when rated by the same person, these constructs have significant overlap and lack discreteness. Future directions for study of the therapeutic relationship are discussed. Implications for practice are provided. PMID- 27389665 TI - Review: Gout: A Roadmap to Approaches for Improving Global Outcomes. PMID- 27389667 TI - Assessment of the Incorporation of Patient-Centric Outcomes in Studies of Minimally Invasive Glaucoma Surgical Devices. AB - IMPORTANCE: Minimally invasive glaucoma surgical (MIGS) devices are one option for lowering intraocular pressure in patients with glaucoma. OBJECTIVE: To examine how often existing clinical studies of MIGS devices registered on ClinicalTrials.gov measure patient-centric outcomes that patients value directly. DESIGN, SETTING, AND PARTICIPANTS: We searched ClinicalTrials.gov, a registry of publicly and privately supported clinical studies, on February 20, 2015, for records of MIGS device studies involving patients with glaucoma. Two investigators independently abstracted study design and outcome details from eligible records. We classified outcomes as patient-centric or not patient centric using a prespecified definition. MAIN OUTCOMES AND MEASURES: Proportion of patient-centric and nonpatient-centric outcomes registered on ClinicalTrials.gov. RESULTS: We identified 51 eligible studies specifying 127 outcomes. Reduction in intraocular pressure was the most frequent outcome specified (78/127; 61%) and a primary outcome in 41 studies. Patient-centric outcomes-such as adverse events (n = 19; 15%), topical medication use (n = 16; 13%), visual acuity (n = 4; 3%), and health-related quality of life (n = 1; 1%) were less frequently specified (n = 40; 32%) and a primary outcome in only 12 studies. CONCLUSION AND RELEVANCE: Patient-centric outcomes that provide insight into the relative desirability and acceptability of the benefits and risks of MIGS devices are not well represented in current clinical studies. PMID- 27389668 TI - Bayesian prospective detection of small area health anomalies using Kullback Leibler divergence. AB - Early detection of unusual health events depends on the ability to rapidly detect any substantial changes in disease, thus facilitating timely public health interventions. To assist public health practitioners to make decisions, statistical methods are adopted to assess unusual events in real time. We introduce a surveillance Kullback-Leibler measure for timely detection of disease outbreaks for small area health data. The detection methods are compared with the surveillance conditional predictive ordinate within the framework of Bayesian hierarchical Poisson modeling and applied to a case study of a group of respiratory system diseases observed weekly in South Carolina counties. Properties of the proposed surveillance techniques including timeliness and detection precision are investigated using a simulation study. PMID- 27389669 TI - Exact confidence limits for the response rate in two-stage designs with over- or under-enrollment in the second stage. AB - Simon's two-stage design has been widely used in early phase clinical trials to assess the activity of a new investigated treatment. In practice, the actual sample sizes do not always follow the study design precisely, especially in the second stage. When over- or under-enrollment occurs in a study, the original critical values for the study design are no longer valid for making proper statistical inference in a clinical trial. The hypothesis for such studies is always one-sided, and the null hypothesis is rejected when only a few responses are observed. Therefore, a one-sided lower interval is suitable to test the hypothesis. The commonly used approaches for confidence interval construction are based on asymptotic approaches. These approaches generally do not guarantee the coverage probability. For this reason, Clopper-Pearson approach can be used to compute exact confidence intervals. This approach has to be used in conjunction with a method to order the sample space. The frequently used method is based on point estimates for the response rate, but this ordering has too many ties which lead to conservativeness of the exact intervals. We propose developing exact one sided intervals based on the p-value to order the sample space. The proposed approach outperforms the existing asymptotic and exact approaches. Therefore, it is recommended for use in practice. PMID- 27389670 TI - Semiparametric models for multilevel overdispersed count data with extra zeros. AB - This study proposes semiparametric models for analysis of hierarchical count data containing excess zeros and overdispersion simultaneously. The methods discussed in this paper handle nonlinear covariate effects through flexible semiparametric multilevel regression techniques. This is performed by providing a comprehensive comparison of semiparametric multilevel zero-inflated negative binomial and semiparametric multilevel zero-inflated generalized Poisson models under the real and simulated data. An EM algorithm based on Newton-Raphson equations for maximum penalized likelihood estimation approach is developed. The performance of the proposed models is assessed by using a Monte Carlo simulation study. We also illustrated the methods by the analysis of decayed, missing, and filled teeth of children aged 5-14 years old. PMID- 27389671 TI - Hearing the Signs of Age-Related Cognitive Decline: A Commentary on "Hearing Aid Use Is Associated with Better Mini-Mental State Exam Performance". PMID- 27389672 TI - Agitation in Alzheimer Disease as a Qualifying Condition for Medical Marijuana in the United States. AB - OBJECTIVE: To determine the extent to which states and localities include dementia as a qualifying condition for medical marijuana and how common this indication is. METHODS: The authors reviewed authorizing legislation and medical marijuana program websites and annual reports for the states and localities where medical marijuana is legal. RESULTS: Of the 24 states and localities where medical marijuana is legal, dementia is a qualifying condition in 10 (41.7%), primarily for agitation of Alzheimer disease. In the five states where information was available regarding qualifying conditions for certification, dementia was the indication for <0.5% of medical marijuana certifications. CONCLUSION: Dementia is somewhat commonly listed as a potential qualifying condition for medical marijuana. Currently, few applicants for medical marijuana list dementia as the reason for seeking certification. However, given increasingly open attitudes toward recreational and medical marijuana use, providers should be aware that dementia is a potential indication for licensing, despite lack of evidence for its efficacy. PMID- 27389673 TI - Addressing Purpose and Meaning of Life in the Clinical Setting. PMID- 27389674 TI - Milestones in Pancreas Transplantation in Belgium. PMID- 27389675 TI - Effectiveness of Fractionated Plasma Separation and Absorption as a Treatment for Amanita Phalloides Poisoning. AB - BACKGROUND Fractionated plasma separation and absorption (FPSA) is an extracorporeal liver support method that detoxifies accumulated toxins. There are limited data of its use in the treatment of Amanita phalloides intoxication. The objective of this study was to investigate whether FPSA before liver transplantation improves patients' short-term post liver transplantation survival in Amanita phalloides poisoning. MATERIAL AND METHODS The study population consisted of ten patients who had liver transplantation (LT) due to acute liver failure (ALF) caused by Amanita phalloides poisoning. Six patients were treated with FPSA before liver transplantation. All the patients who were started on FPSA were also placed on the liver transplantation list according to emergent liver transplantation criteria. RESULTS Patients treated with FPSA were in a more severe clinical condition presenting in higher mean MELD, total bilirubin, INR and ammonia along with more frequent hypoglycemia and hepatic encephalopathy grade 3/4. FPSA group had longer mean waiting time on the recipient list (3.5 vs. 1.25 days) but inferior thirty-day survival rate (16.5% vs. 100%). CONCLUSIONS When conservative medical modalities are ineffective, the only treatment for Amanita phalloides poisoning is a liver transplant. Although FPSA treated patients had inferior post-LT survival, FPSA was found to prolong the pre surgical waiting time for critically ill patients, consequently giving a chance of life-saving procedure. PMID- 27389677 TI - Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress. AB - The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain. PMID- 27389676 TI - Morphological Changes in the Carotid Artery Intima after Gastric Bypass for Morbid Obesity. AB - BACKGROUND: Carotid intima-media thickness (C-IMT) can be considered as an early marker of atherosclerosis, thus representing a reliable cardiovascular risk predictor. Bariatric surgery decreases the burden of cardiovascular disease in obese patients through complex mechanisms, of which weight loss is merely the most evident epiphenomenon. The aim of this study is to evaluate C-IMT variations in patients undergoing Roux-en-Y gastric bypass (RYGB) and possible correlations with biometric parameters and cardiovascular risk factors. METHODS: Thirty patients undergoing RYGB for morbid obesity were enrolled for carotid artery B mode ultrasound evaluation before surgery and at 1-, 3-, 6-, and 12-month follow up; C-IMT was recorded at three levels (bulb, common, and internal carotid). At each one of the follow-ups, biometric and serohematic parameters were also collected. RESULTS: The 22 patients who completed the follow-up and were included in the study showed significant C-IMT reduction at all three levels at 12-month follow-up (p < 0.001). Along with a significant BMI reduction and diabetes/hypertension remission, we found a considerable decrease in total cholesterol (219 vs 164 mg/dl; p < 0.001) and uric acid (5.6 vs 4.5 mg/dl; p < 0.01) and a significant increase in HDL cholesterol (43.9vs59.2 mg/dl; p < 0.001). The data imply that the mean 10-year cardiovascular risk score drops by nearly 50 % (5.7 +/- 5.6 vs. 2.9 +/- 2.7 %, p < 0.001) according to Framingham cardiovascular risk stratification. CONCLUSIONS: RYGB is associated with significant decrease in C-IMT at 1 year. Pathophysiologic processes underlying such a variation, probably involving lipid and urate metabolism and their correlation with cardiovascular risk reduction should be confirmed by long-term prospective trials. PMID- 27389678 TI - A randomized controlled trial comparing single-incision laparoscopic cholecystectomy using a novel instrument to that using a common instrument. AB - BACKGROUND: To evaluate the safety and feasibility of single incision laparoscopic cholecystectomy (SILC) using a novel instrument. MATERIALS AND METHODS: From September 2011 to June 2012, eligible patients (150 cases) were divided randomly into three groups: group A, SILC using a novel instrument; group B, SILC using a conventional instrument; and group C, conventional laparoscopic cholecystectomy (LC). Operative and postoperative outcomes were analyzed. RESULTS: The operative times for Group A [mean 40 min; rang 30-50 min] and Group B [mean 37.5 min; rang 25-50 min] demonstrated no significant differences (P = 0.610), but both times were longer than that in Group C [mean 25 min; rang 20-35 min] (Z = 25.165, P = 0.000; Z = 16.184, P = 0.000). There was no significant difference between the level of blood loss in Group A [mean 10.0 ml; range 5.0 20.0 ml] and Group B [mean 10.0 ml; range 5.0-20.0 ml] (P = 0.989), but the level in both groups was higher than that in Group C [mean 7.5 ml; range 5.0-10.0 ml] (Z = 12.571, P = 0.002; Z = 13.619, P = 0.001). There were no significant differences in patient satisfaction and pain scores (P = 0.519; P = 0.691) among the three groups. Complications occurred in 4 cases, including 1 case of bile injury and 3 cases of bile leakage. There were no complications in SILC with a novel instrument. CONCLUSIONS: SILC require a longer operative time and more blood loss without benefit of patient satisfaction and pain scores. However, SILC with a novel instrument has fewer complications and a tendency to safer than SILC with a conservative instrument, and it could be a possible alternative in cholecystectomy. PMID- 27389679 TI - Role in proinflammatory response of YghJ, a secreted metalloprotease from neonatal septicemic Escherichia coli. AB - Neonatal sepsis is the invasion of microbial pathogens into blood stream and is associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. The increased serum levels of cytokines were found to correlate with the severity and mortality in course of sepsis. There have been no reports on the role of microbial proteases in stimulation of proinflammatory response in neonatal sepsis. We have identified YghJ, a secreted metalloprotease from a neonatal septicemic Escherichia coli (NSEC) isolate. The protease was partially purified from culture supernatant by successive anion and gel filtration chromatography. MS/MS peptide sequencing of the protease showed homology with YghJ. YghJ was cloned, expressed and purified in pBAD TOPO expression vector. YghJ was found to be proteolytically active against Methoxysuccinyl Ala-Ala-Pro-Met-p-nitroanilide oligopeptide substrate, but not against casein and gelatin. YghJ showed optimal activity at pH 7-8 and at temperatures 37-40 degrees C. YghJ showed clear changes in cellular morphologies of Int407, HT-29 and HEK293 cells. YghJ stimulated the secretion of cytokines IL 1alpha, IL-1beta and TNF-alpha in murine macrophages (RAW 264.7) and IL-8 from human intestinal epithelial cells (HT-29). YghJ also down-regulated the production of anti-inflammatory cytokines such as IL-10. YghJ is present in both septicemic (78%) and fecal E. coli isolates (54%). However, expression and secretion of YghJ is significantly higher among the septicemic (89%) than the fecal isolates (33%). This is the first study to show the role of a microbial protease, YghJ in triggering proinflammatory response in NSEC. PMID- 27389680 TI - 2016 ISCB Innovator Award: Serafim Batzoglou. PMID- 27389681 TI - Dose-response efficacy and safety of PA21 in Japanese hemodialysis patients with hyperphosphatemia: a randomized, placebo-controlled, double-blind, Phase II study. AB - BACKGROUND: Hyperphosphatemia is common in chronic kidney disease (CKD) and associated with mortality and morbidity. We aimed to evaluate the dose-dependent efficacy and safety of PA21 (sucroferric oxyhydroxide), an iron-based phosphate binder, in Japanese hemodialysis patients with hyperphosphatemia. METHODS: In this double-blind, multicenter, Phase II study, 183 patients were randomized to placebo or PA21 at doses of 250, 500, 750, or 1000 mg (based on iron content) three times/day for 6 weeks. The primary efficacy endpoint was the mean change in serum phosphorus levels from baseline to end of treatment in each group. Adverse reactions were evaluated. RESULTS: The change in serum phosphorus level was significantly greater in each PA21 group than in the placebo group (analysis of covariance: P < 0.001 for all groups). A dose-dependent change in serum phosphorus levels was observed in the PA21 groups. A notable decrease in mean serum phosphorus levels to the target level of <=6 mg/dL was shown starting at Week 1 in all PA21 groups. The cumulative achievement rates for target serum phosphorus level at the end of treatment were generally >80 % in all PA21 groups. The major adverse reaction reported was diarrhea; however, most cases were mild. CONCLUSIONS: PA21 was an effective and safe treatment that decreased serum phosphorus levels starting at 1 week of treatment when administered as one 250-mg tablet three times/day. PA21 demonstrated a dose-dependent phosphorus lowering effect up to 3000 mg/day. PA21 may be a new treatment alternative with relatively low pill burden for Japanese hemodialysis patients with hyperphosphatemia. PMID- 27389682 TI - Species-Specific Detection of Mycosphaerella polygoni-cuspidati as a Biological Control Agent for Fallopia japonica by PCR Assay. AB - The ascomycete fungus Mycosphaerella polygoni-cuspidati has been undergoing evaluation as a potential classical biological control agent for the invasive weed Fallopia japonica (Japanese knotweed), which has become troublesome in Europe and North America. In advance of the potential release of a biocontrol agent into a new environment, it is crucial to develop an effective monitoring system to enable the evaluation of agent establishment and dispersal within the target host population, as well as any potential attacks on non-target species. Therefore, a primer pair was designed for direct, rapid, and specific detection of the Japanese knotweed pathogen M. polygoni-cuspidati based on the sequences of the internal transcribed spacer regions including the 5.8S rDNA. A PCR product of approximately 298 bp was obtained only when the DNA extracted from mycelial fragments of M. polygoni-cuspidati was used. The lower limit of detection of the PCR method was 100 fg of genomic DNA. Using the specific primer pair, M. polygoni cuspidati could be detected from both naturally and artificially infected Japanese knotweed plants. No amplification was observed for other Mycosphaerella spp. or fungal endophytes isolated from F. japonica. The designed primer pair is thus effective for the specific detection of M. polygoni-cuspidati in planta. PMID- 27389683 TI - Effects of Transgenic Bt Rice on Nontarget Rhopalosiphum maidis (Homoptera: Aphididae). AB - The effects of three transgenic Bacillus thuringiensis (Bt) rice lines, KMD1, KMD2, and G8-7, on biological parameters and population dynamics of nontarget insect, Rhopalosiphum maidis (Fitch) (Homoptera: Aphididae), were investigated in the laboratory and field. No significant differences were found between Bt and non-Bt rice lines for aphid survival. The developmental time of R. maidis that fed on KMD1 and KMD2 did not differ significantly from those of the individuals feeding on the parental variety Xiushui11, but significantly prolonged developmental time was observed on G8-7 as compared with its parental variety Xiushui110. Aphid fecundity was significantly higher on Bt than on parental rice. A 2-yr field survey indicated that Bt rice did not significantly affect the population dynamics of R. maidis in comparison with non-Bt rice. Additionally, guttation droplets of Bt rice and aphids feeding on Bt rice were analyzed for presence of Cry1Ab using ELISA. No Cry1Ab protein was found in aphid adults feeding on Bt rice lines both in the laboratory and field. By using the guttation droplets from the top of rice seedlings, we designed a novel method to collect phloem sap, and found that relatively low concentrations were detected in the guttation droplets from Bt rice lines. In conclusion, although the Bt rice lines tested in this study stimulate the fecundity of R. maidis, the aphid population density did not increase in Bt rice fields. PMID- 27389684 TI - Leaf-level photosynthetic capacity in lowland Amazonian and high-elevation Andean tropical moist forests of Peru. AB - We examined whether variations in photosynthetic capacity are linked to variations in the environment and/or associated leaf traits for tropical moist forests (TMFs) in the Andes/western Amazon regions of Peru. We compared photosynthetic capacity (maximal rate of carboxylation of Rubisco (Vcmax ), and the maximum rate of electron transport (Jmax )), leaf mass, nitrogen (N) and phosphorus (P) per unit leaf area (Ma , Na and Pa , respectively), and chlorophyll from 210 species at 18 field sites along a 3300-m elevation gradient. Western blots were used to quantify the abundance of the CO2 -fixing enzyme Rubisco. Area- and N-based rates of photosynthetic capacity at 25 degrees C were higher in upland than lowland TMFs, underpinned by greater investment of N in photosynthesis in high-elevation trees. Soil [P] and leaf Pa were key explanatory factors for models of area-based Vcmax and Jmax but did not account for variations in photosynthetic N-use efficiency. At any given Na and Pa , the fraction of N allocated to photosynthesis was higher in upland than lowland species. For a small subset of lowland TMF trees examined, a substantial fraction of Rubisco was inactive. These results highlight the importance of soil- and leaf P in defining the photosynthetic capacity of TMFs, with variations in N allocation and Rubisco activation state further influencing photosynthetic rates and N-use efficiency of these critically important forests. PMID- 27389685 TI - Pitfalls of the Geographic Population Structure (GPS) Approach Applied to Human Genetic History: A Case Study of Ashkenazi Jews. AB - In a recent interdisciplinary study, Das et al. have attempted to trace the homeland of Ashkenazi Jews and of their historical language, Yiddish (Das et al. 2016 Localizing Ashkenazic Jews to Primeval Villages in the Ancient Iranian Lands of Ashkenaz. Genome Biol Evol. 8:1132-1149). Das et al. applied the geographic population structure (GPS) method to autosomal genotyping data and inferred geographic coordinates of populations supposedly ancestral to Ashkenazi Jews, placing them in Eastern Turkey. They argued that this unexpected genetic result goes against the widely accepted notion of Ashkenazi origin in the Levant, and speculated that Yiddish was originally a Slavic language strongly influenced by Iranian and Turkic languages, and later remodeled completely under Germanic influence. In our view, there are major conceptual problems with both the genetic and linguistic parts of the work. We argue that GPS is a provenancing tool suited to inferring the geographic region where a modern and recently unadmixed genome is most likely to arise, but is hardly suitable for admixed populations and for tracing ancestry up to 1,000 years before present, as its authors have previously claimed. Moreover, all methods of historical linguistics concur that Yiddish is a Germanic language, with no reliable evidence for Slavic, Iranian, or Turkic substrata. PMID- 27389686 TI - When Genomics Is Not Enough: Experimental Evidence for a Decrease in LINE-1 Activity During the Evolution of Australian Marsupials. AB - The autonomous transposable element LINE-1 is a highly abundant element that makes up between 15% and 20% of therian mammal genomes. Since their origin before the divergence of marsupials and placental mammals, LINE-1 elements have contributed actively to the genome landscape. A previous in silico screen of the Tasmanian devil genome revealed a lack of functional coding LINE-1 sequences. In this study we present the results of an in vitro analysis from a partial LINE-1 reverse transcriptase coding sequence in five marsupial species. Our experimental screen supports the in silico findings of the genome-wide degradation of LINE-1 sequences in the Tasmanian devil, and identifies a high frequency of degraded LINE-1 sequences in other Australian marsupials. The comparison between the experimentally obtained LINE-1 sequences and reference genome assemblies suggests that conclusions from in silico analyses of retrotransposition activity can be influenced by incomplete genome assemblies from short reads. PMID- 27389687 TI - Genome Evolution in the Obligate but Environmentally Active Luminous Symbionts of Flashlight Fish. AB - The luminous bacterial symbionts of anomalopid flashlight fish are thought to be obligately dependent on their hosts for growth and share several aspects of genome evolution with unrelated obligate symbionts, including genome reduction. However, in contrast to most obligate bacteria, anomalopid symbionts have an active environmental phase that may be important for symbiont transmission. Here we investigated patterns of evolution between anomalopid symbionts compared with patterns in free-living relatives and unrelated obligate symbionts to determine if trends common to obligate symbionts are also found in anomalopid symbionts. Two symbionts, "Candidatus Photodesmus katoptron" and "Candidatus Photodesmus blepharus," have genomes that are highly similar in gene content and order, suggesting genome stasis similar to ancient obligate symbionts present in insect lineages. This genome stasis exists in spite of the symbiont's inferred ability to recombine, which is frequently lacking in obligate symbionts with stable genomes. Additionally, we used genome comparisons and tests of selection to infer which genes may be particularly important for the symbiont's ecology compared with relatives. In keeping with obligate dependence, substitution patterns suggest that most symbiont genes are experiencing relaxed purifying selection compared with relatives. However, genes involved in motility and carbon storage, which are likely to be used outside the host, appear to be under increased purifying selection. Two chemoreceptor chemotaxis genes are retained by both species and show high conservation with amino acid sensing genes, suggesting that the bacteria may actively seek out hosts using chemotaxis toward amino acids, which the symbionts are not able to synthesize. PMID- 27389688 TI - Comparison of a Modern and Fossil Pithovirus Reveals Its Genetic Conservation and Evolution. AB - Most theories on viral evolution are speculative and lack fossil comparison. Here, we isolated a modern Pithovirus-like virus from sewage samples. This giant virus, named Pithovirus massiliensis, was compared with its prehistoric counterpart, Pithovirus sibericum, found in Siberian permafrost. Our analysis revealed near-complete gene repertoire conservation, including horizontal gene transfer and ORFans. Furthermore, all orthologous genes evolved under strong purifying selection with a non-synonymous and synonymous ratio in the same range as the ratio found in the prokaryotic world. The comparison between fossil and modern Pithovirus species provided an estimation of the cadence of the molecular clock, reaching up to 3 * 10(-6) mutations/site/year. In addition, the strict conservation of HGTs and ORFans in P. massiliensis revealed the stable genetic mosaicism in giant viruses and excludes the concept of a bag of genes. The genetic stability for 30,000 years of P. massiliensis demonstrates that giant viruses evolve similarly to prokaryotes by classical mechanisms of evolution, including selection and fixation of genes, followed by selective constraints. PMID- 27389689 TI - Identification of Multiple Forms of RNA Transcripts Associated with Human Specific Retrotransposed Gene Copies. AB - The human genome contains thousands of retrocopies, mostly as processed pseudogenes, which were recently shown to be prevalently transcribed. In particular, those specifically acquired in the human lineage are able to modulate gene expression in a manner that contributed to the evolution of human-specific traits. Therefore, knowledge of the human-specific retrocopies that are transcribed or their full-length transcript structure contributes to better understand human genome evolution. In this study, we identified 16 human-specific retrocopies that harbor 5' CpG islands by in silico analysis and showed that 12 were transcribed in normal tissues and cancer cell lines with a variety of expression patterns, including cancer-specific expression. Determination of the structure of the transcripts associated with the retrocopies revealed that none were transcribed from their 5' CpG islands, but rather, from inside the 3' UTR and the nearby 5' flanking region of the retrocopies as well as the promoter of neighboring genes. The multiple forms of the transcripts, such as chimeric and individual transcripts in both the sense and antisense orientation, might have introduced novel post-transcriptional regulation into the genome during human evolution. These results shed light on the potential role of human-specific retrocopies in the evolution of gene regulation and genomic disorders. PMID- 27389690 TI - Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones. AB - Cnidarians represent one of the few groups of venomous animals that lack a centralized venom transmission system. Instead, they are equipped with stinging capsules collectively known as nematocysts. Nematocysts vary in abundance and type across different tissues; however, the venom composition in most species remains unknown. Depending on the tissue type, the venom composition in sea anemones may be vital for predation, defense, or digestion. Using a tissue specific RNA-seq approach, we characterize the venom assemblage in the tentacles, mesenterial filaments, and column for three species of sea anemone (Anemonia sulcata, Heteractis crispa, and Megalactis griffithsi). These taxa vary with regard to inferred venom potency, symbiont abundance, and nematocyst diversity. We show that there is significant variation in abundance of toxin-like genes across tissues and species. Although the cumulative toxin abundance for the column was consistently the lowest, contributions to the overall toxin assemblage varied considerably among tissues for different toxin types. Our gene ontology (GO) analyses also show sharp contrasts between conserved GO groups emerging from whole transcriptome analysis and tissue-specific expression among GO groups in our differential expression analysis. This study provides a framework for future characterization of tissue-specific venom and other functionally important genes in this lineage of simple bodied animals. PMID- 27389692 TI - Incidentally Detected Lithopedion in an 87-Year-Old Lady: An Autopsy Case Report. AB - A lithopedion is a rare complication of pregnancy that occurs when a fetus in an intraabdominal location dies, and it is too large to be reabsorbed by the body. The case was an 87-year-old woman, and she was transferred to the morgue department in April 2014 to determine the cause of death. During autopsy, an intraabdominally located calcified dead fetus and a 12-cm diameter calcified cyst in the right ovary were incidentally detected. It was aged 25 to 29 weeks (according to femur and humerus measurements) with a size of 12.5 * 8 * 5 cm and a weight of 227 g. According to investigation reports, her husband died in 1990, and she had 3 deliveries, the most recent of which was in 1946. Because the menopause age of the case was not exactly known, the retention time of the lithopedion was supposed to be 24 to 68 years according to the date of the most recent pregnancy and the date of her spouse's death. It is the first case that has been incidentally detected and identified during an autopsy in Turkey and also one of the oldest cases in the literature. PMID- 27389691 TI - Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism. AB - Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a beta-carotene or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that beta-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. PMID- 27389693 TI - What Makes a Good Palliative Care Physician? A Qualitative Study about the Patient's Expectations and Needs when Being Admitted to a Palliative Care Unit. AB - OBJECTIVE: The aims of the study were to examine a) patients' knowledge of palliative care, b) patients' expectations and needs when being admitted to a palliative care unit, and c) patient's concept of a good palliative care physician. METHODS: The study was based on a qualitative methodology, comprising 32 semistructured interviews with advanced cancer patients admitted to the palliative care unit of the Medical University of Vienna. Interviews were conducted with 20 patients during the first three days after admission to the unit and after one week, recorded digitally, and transcribed verbatim. Data were analyzed using NVivo 10 software, based on thematic analysis enhanced with grounded theory techniques. RESULTS: The results revealed four themes: (1) information about palliative care, (2) supportive care needs, (3) being treated in a palliative care unit, and (4) qualities required of palliative care physicians. The data showed that patients lack information about palliative care, that help in social concerns plays a central role in palliative care, and attentiveness as well as symptom management are important to patients. Patients desire a personal patient-physician relationship. The qualities of a good palliative care physician were honesty, the ability to listen, taking time, being experienced in their field, speaking the patient's language, being human, and being gentle. Patients experienced relief when being treated in a palliative care unit, perceived their care as an interdisciplinary activity, and felt that their burdensome symptoms were being attended to with emotional care. Negative perceptions included the overtly intense treatment. CONCLUSIONS: The results of the present study offer an insight into what patients expect from palliative care teams. Being aware of patient's needs will enable medical teams to improve professional and individualized care. PMID- 27389694 TI - [Not Available]. PMID- 27389695 TI - [Not Available]. PMID- 27389696 TI - PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-beta1 Pathway. AB - The pregnancy-specific glycoproteins (PSGs) are a family of proteins secreted by the syncytiotrophoblast of the placenta and are the most abundant trophoblastic proteins in maternal blood during the third trimester. The human PSG family consists of 10 protein-coding genes, some of which have a possible role in maintaining maternal immune tolerance to the fetus. PSG9 was reported as a potential predictive biomarker of pre-eclampsia, a serious complication of pregnancy that has been related to immunological dysfunction at the fetal maternal interface. Therefore, we hypothesized that PSG9 may have an immunoregulatory role during pregnancy. We found that PSG9 binds to LAP and activates the latent form of TGF-beta1. In addition, PSG9 induces the secretion of TGF-beta1 from macrophages but not from CD4+ T-cells. TGF-beta1 is required for the ex vivo differentiation of regulatory T-cells and, consistent with the ability of PSG9 to activate this cytokine, we observed that PSG9 induces the differentiation of FoxP3+ regulatory T-cells from naive murine and human T-cells. Cytokines that are associated with inflammatory responses were also reduced in the supernatants of T-cells treated with PSG9, suggesting that PSG9, through its activation of TGFbeta-1, could be a potent inducer of immune tolerance. PMID- 27389697 TI - Obesity or smoking: Which factor contributes more to the incidence of myocardial infarction? Authors' Reply. PMID- 27389698 TI - Determinants of thromboxane biosynthesis in patients with moderate to severe chronic kidney disease. AB - BACKGROUND: Mechanisms of accelerated atherothrombosis in patients with chronic kidney disease (CKD) are only partly characterized. The aims of this study were to evaluate the extent of thromboxane (TX)-dependent platelet activation in patients with CKD, and to characterize the determinants of altered TX biosynthesis in this setting, with particular reference to enhanced lipid peroxidation, low grade inflammation and CKD-related anemia. PATIENTS AND METHODS: A cross sectional comparison between urinary 8-iso-PGF2alpha and 11 dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, was performed in 115 patients with stage 1-4 CKD. RESULTS: Levels of both urinary 11-dehydro-TXB2 and 8-iso-PGF2alpha increased sequentially across the four CKD stages (P<0.0001, Kruskal-Wallis test). Both urinary prostanoids were inversely associated with either estimated glomerular filtration rate (eGFR, P<0.0001) or hemoglobin levels (P<0.0001). A significant direct correlation was also observed between urinary 11-dehydro-TXB2 and 8-iso-PGF2alpha (Rho=0.620, P<0.0001). On multivariate analysis, urinary 8-iso-PGF2alpha (beta=0.459, P<0.0001), hemoglobin levels (beta=- 0.261, P=0.002) and eGFR (beta=-0.172, P=0.032) were independent predictors of urinary 11-dehydro-TXB2 (adjusted R(2)=0.488). CONCLUSIONS: This study provides biochemical evidence of persistent platelet activation in patients with CKD. This condition occurs early in the natural history of the disease and is related to kidney function and oxidative stress. Moreover, we found an independent inverse relationship between hemoglobin levels and TX-dependent platelet activation. This finding may provide a mechanistic link between CKD-related anemia and increased cardiovascular risk. PMID- 27389699 TI - New Thieme Research Awards: Call for Pacesetting Contributions to Drug Research. PMID- 27389700 TI - Genome-wide Association Study Identifies Loci for the Polled Phenotype in Yak. AB - The absence of horns, known as the polled phenotype, is an economically important trait in modern yak husbandry, but the genomic structure and genetic basis of this phenotype have yet to be discovered. Here, we conducted a genome-wide association study with a panel of 10 horned and 10 polled yaks using whole genome sequencing. We mapped the POLLED locus to a 200-kb interval, which comprises three protein-coding genes. Further characterization of the candidate region showed recent artificial selection signals resulting from the breeding process. We suggest that expressional variations rather than structural variations in protein probably contribute to the polled phenotype. Our results not only represent the first and important step in establishing the genomic structure of the polled region in yak, but also add to our understanding of the polled trait in bovid species. PMID- 27389701 TI - Annexin A2 Modulates ROS and Impacts Inflammatory Response via IL-17 Signaling in Polymicrobial Sepsis Mice. AB - Sepsis is a progressive disease manifesting excessive inflammatory responses, severe tissue injury, organ dysfunction, and, ultimately, mortality. Since currently, there are limited therapeutic options for this disease, further understanding the molecular pathogenesis of sepsis may help develop effective treatments. Here we identify a novel role for Annexin A2 (AnxA2), a multi compartmental protein, in inhibiting pro-inflammatory response by regulating reactive oxygen species (ROS) and IL-17 signaling during sepsis. In cecal ligation and puncture (CLP) sepsis models, anxa2-/- mice manifested increased pro inflammatory cytokines and neutrophil infiltration, but decreased bacterial clearance and animal survival. In addition, AnxA2 deficiency led to intensified ROS and IL-17A. Using site directed mutagenesis, we uncovered that cysteine 9 of AnxA2 was the most important aa (site) for regulation of ROS levels. Furthermore, ROS appears to be responsible for elevated IL-17A levels and subsequently exaggerated inflammatory response. Depletion of IL-17 via CRISPR/Cas9 KO strategy down-regulated inflammation and conferred protection against sepsis in anxa2-/- mice. Our findings reveal a previously undemonstrated function for AnxA2 in inflammatory response in polymicrobial sepsis models via an AnxA2-ROS-IL-17 axis, providing insight into the regulation of pathophysiology of sepsis. PMID- 27389703 TI - Design of iron oxide-based nanoparticles for MRI and magnetic hyperthermia. AB - Iron oxide nanoparticles are widely used for biological applications thanks to their outstanding balance between magnetic properties, surface-to-volume ratio suitable for efficient functionalization and proven biocompatibility. Their development for MRI or magnetic particle hyperthermia concentrates much of the attention as these nanomaterials are already used within the health system as contrast agents and heating mediators. As such, the constant improvement and development for better and more reliable materials is of key importance. On this basis, this review aims to cover the rational design of iron oxide nanoparticles to be used as MRI contrast agents or heating mediators in magnetic hyperthermia, and reviews the state of the art of their use as nanomedicine tools. PMID- 27389704 TI - Special issue: Stress responses. PMID- 27389702 TI - Effects of Oxaliplatin Treatment on the Enteric Glial Cells and Neurons in the Mouse Ileum. AB - Oxaliplatin, currently used for treatment of colorectal and other cancers, causes severe gastrointestinal side effects, including nausea, vomiting, diarrhea, and constipation that are attributed to mucosal damage. However, delayed onset and long-term persistence of these side effects suggest that damage to the enteric nervous system (ENS) regulating physiological function of the gastrointestinal tract may also occur. The ENS comprises myenteric and submucosal neurons and enteric glial cells (EGCs). This study aimed to investigate the effects of oxaliplatin treatment on enteric neurons and EGCs within the mouse ileum. BALB/c mice received repeated intraperitoneal injections of oxaliplatin (3 mg/kg, 3 injections/week). Tissues were collected 3, 7, 14, and 21 days from the commencement of treatment. Decreases in glial fibrillary acidic protein immunoreactive (IR) EGCs and protein gene product 9.5/beta-Tubulin III-IR neurons as well as increase in s100beta-IR EGCs after chronic oxaliplatin administration were observed in both the myenteric and submucosal plexi. Changes in EGCs were further observed in cross-sections of the ileum at day 14 and confirmed by Western blotting. Alterations in EGCs correlated with loss of myenteric and submucosal neurons in the ileum from oxaliplatin-treated mice. These changes to the ENS may contribute to the mechanisms underlying gastrointestinal side effects associated with oxaliplatin treatment. PMID- 27389705 TI - Determining the disability adjusted life years lost to childhood and adolescence epilepsy in southeast Nigeria: An exploratory study. AB - OBJECTIVES: Disease burden has always been based on associated mortality. An accurate measurement of the burden of epilepsy should rely on both morbidity and mortality. This will close any existing gap in knowledge and provide useful information to aid evidence-based decision-making. In this study, burden of epilepsy was estimated, using disability-adjusted-life-years (DALYs), using disability weights for epilepsy that were part of the Global Burden of Disease 2010 work. METHODS: The study was conducted at the University of Nigeria Teaching Hospital, Enugu. Interviewer-administered questionnaire was used to collect information from patients with epilepsy who presented to neurology clinic. The prevalence of epilepsy, and case-fatality were obtained from previous publications. The DALYs were estimated by adding together the years lost to disability (YLDs) and years lost to life (YLLs) to epilepsy (DALYs=YLD+YLL). DALYs were dis-aggregated by age group and by whether or not epilepsy was treated. RESULTS: A total of 134 children with epilepsy-interviews were conducted. Some 56% and 44% of the subjects had primary and secondary epilepsy, respectively. The childhood epilepsy caused 1.63 YLLs per 1000 population, 0.45 YLDs per 1000 population and 2.08 DALY per 1000 population. The highest burden was in children within the age group of 5-14 years at 2.18 DALY per 1000 people. The YLDs was higher (0.63/1000 population) among the untreated group, compared with the YLDs (0.27/1000 population) among the treated group. The YLLs lost for children with secondary epilepsy (2.23/1000 population) was higher than primary epilepsy YLLs of 1.07/1000 population. SIGNIFICANCE: The DALYs due to childhood epilepsy was high. The YLDs was high among children with epilepsy who were not on treatment. The YLLs were found to be the same in all children with epilepsy, irrespective of their treatment status. This imperatively necessitates the de emphasis on just mortality as an indicator of the burden of childhood epilepsy but rather a holistic approach should be adopted in considering both the mortality and disability in monitoring the outcome of health interventions. PMID- 27389706 TI - Patients with dravet syndrome in the era of stiripentol: A French cohort cross sectional study. AB - OBJECTIVE: The aim of this study was to assess outcome and seizure response to treatment with stiripentol (STP) associated to valproate (VPA) and clobazam (CLB), which we have used in our center since the 1990s, in patients with Dravet syndrome (DS). METHODS: We performed a cross-sectional study of all DS patients with SCN1A mutations who had at least one visit to our center in 2013. A total of 54 patients were included (32 males, 22 females), whose ages ranged from 2.5 to 22 years. RESULTS: Seizure onset ranged from 2 to 9 months (mean 5 months). Treatment started at a mean age of 7 months with valproate (VPA) as first therapy in 83% of patients. STP was prescribed in 96% at an average age of 20 months. At last follow-up (up to 22 years, median 8 years), 96% were still receiving STP, with VPA and clobazam (CLB) in 91%. Additional therapies were prescribed in 72% of patients. Most patients (96%) continued to have clonic or tonic-clonic seizures but they were brief (<5min, with last status epilepticus (SE) episode being before 4 years of age). Seizures occurred weekly (>3/month) in 38% of patients, monthly (1-3/month) in 40%, and yearly in the remaining patients. None presented with daily seizures. Seizure frequency at last visit was related to the age of treatment initiation, the age of last SE, and SCN1A mutation type. CONCLUSIONS: Triple therapy with STP, VPA, and CLB was maintained long-term by 96% of this large DS cohort because the reduced frequency and severity of seizures STP provided when added to CLB and VPA was durable. Nevertheless, only a few patients achieved seizure freedom and persisting seizures remains a concern in the majority of patients. PMID- 27389707 TI - A Facile Route to Bimetal and Nitrogen-Codoped 3D Porous Graphitic Carbon Networks for Efficient Oxygen Reduction. AB - Bimetal nitrogen-doped carbon with both Fe and Co, derived from the pyrolysis carbon of iron and cobalt phthalocyanine-based conjugated polymer networks, possesses a few-layer graphene-like texture with hierarchical porosity in meso/micro multimodal pore size distribution. The novel electrocatalyst exhibits Pt-like catalytic activity and much higher catalytic durability for oxygen reduction. PMID- 27389709 TI - Fool Me Once. PMID- 27389708 TI - Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment. AB - Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well suited strategy for bone regenerative therapies. PMID- 27389710 TI - Drug reaction with eosinophilia and systemic symptoms (DRESS) induced by imatinib in chronic myeloid leukemia. PMID- 27389711 TI - Shaken not stirred: A molecular contribution to the systematics of genus Mugil (Teleostei, Mugilidae). AB - With this work we addressed some molecular systematic issues within the Mugil cephalus species complex. Particular attention was paid to the debated situations of: (i) Mugil liza, occurring in partial sympatry with Mugil cephalus in the northwestern Atlantic, and (ii) Mugil platanus, considered by some authors a synonymy of the former species and distributed in the southwestern Atlantic. We sequenced 79 individuals of a 465-bp portion of the mitochondrial control region (CR) from 8 western Atlantic and 2 Mediterranean localities. In addition, all CR sequences available from GenBank for the studied taxa were added to our dataset, for a total of 323 individuals. Overall, 229 haplotypes corresponding to 8 divergent monophyletic lineages were detected. Results of phylogenetic analyses were consistent with the occurrence of past speciation events producing the observed lineages. Of these lineages, 7 correspond to cryptic species and one is constituted by M. liza and M. platanus. As a matter of fact, these 2 taxa constitute a single lineage within the M. cephalus species complex. However, individuals of M. liza/M. platanus lineage analyzed by means of the 18 mitochondrial markers available in GenBank exhibited a degree of genetic diversity consistent with highly divergent populations. Of the 8 lineages detected, the Mediterraean one (type locality) corresponds to M. cephalus; the lineage M. liza/M. platanus should be named M. liza, under the priority principle, and the left 6 lineages need formal description. PMID- 27389712 TI - Crossing Science-Policy-Societal Boundaries to Reduce Scientific and Institutional Uncertainty in Small-Scale Fisheries. AB - The governance of small-scale fisheries (SSF) is challenging due to the uncertainty, complexity, and interconnectedness of social, political, ecological, and economical processes. Conventional SSF management has focused on a centralized and top-down approach. A major criticism of conventional management is the over-reliance on 'expert science' to guide decision-making and poor consideration of fishers' contextually rich knowledge. That is thought to exacerbate the already low governance potential of SSF. Integrating scientific knowledge with fishers' knowledge is increasingly popular and is often assumed to help reduce levels of biophysical and institutional uncertainties. Many projects aimed at encouraging knowledge integration have, however, been unsuccessful. Our objective in this research was to assess factors that influence knowledge integration and the uptake of integrated knowledge into policy-making. We report results from 54 semi-structured interviews with SSF researchers and practitioners from around the globe. Our analysis is framed in terms of scientific credibility, societal legitimacy, and policy saliency, and we discuss cases that have been partially or fully successful in reducing uncertainty via push-and-pull-oriented boundary crossing initiatives. Our findings suggest that two important factors affect the science-policy-societal boundary: a lack of consensus among stakeholders about what constitutes credible knowledge and institutional uncertainty resulting from shifting policies and leadership change. A lack of training for scientific leaders and an apparent 'shelf-life' for community organizations highlight the importance of ongoing institutional support for knowledge integration projects. Institutional support may be enhanced through such investments, such as capacity building and specialized platforms for knowledge integration. PMID- 27389713 TI - Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti-Interferon-Inducible Protein 16 Antibodies. AB - OBJECTIVE: To evaluate whether scleroderma patients who are double-positive for anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and anticentromere (anti-CENP) antibodies are at increased risk for significant digital vascular events relative to patients positive for anti-CENP antibodies alone. METHODS: Sera from 165 scleroderma patients who tested positive for anti-CENP antibodies upon clinical evaluation were reassayed for both anti-CENP and anti-IFI-16 antibodies using enzyme-linked immunosorbent assay testing. Patients who were positive for anti-CENP antibodies alone were then compared to patients who were double-positive for both anti-IFI-16 and anti-CENP antibodies. The association between a history of significant digital vascular events (digital pits, ischemic digital ulcers, and/or gangrene) and double-positive antibody status was examined using chi-square tests. After completion of univariate analysis, multivariable analyses were done to adjust for clinically relevant covariates. RESULTS: Of the 165 anti-CENP antibody positive patients, 21 (12.7%) also had anti-IFI-16 antibodies. Patients who were double-positive for anti-CENP and anti-IFI-16 antibodies were more likely to have had digital pits, ischemic digital ulcers, and/or gangrene (P = 0.03). After adjustment for clinically relevant covariates (age, cutaneous subtype, disease duration, and smoking), double-positive patients remained at significantly higher odds of having severe Raynaud's phenomenon (odds ratio 3.5 [95% confidence interval 1.1-11.1]; P = 0.03). CONCLUSION: Scleroderma patients who are double-positive for antibodies recognizing CENP and IFI-16 are significantly more likely to have significant digital vascular events during the course of their disease. This study provides further evidence that anti-CENP and anti-IFI-16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma. PMID- 27389714 TI - Matrix metalloproteinases-3 gene-promoter polymorphism as a risk factor in oral submucous fibrosis in an Indian population: a pilot study. AB - AIM: Host-related factors could be important to the fundamental understanding of oral diseases. One such factor is matrix metalloproteinases (MMP). MMP3 (stromelysin 1) is crucial in connective tissue remodeling. Promoter regions are specific segments of DNA that control the rate of mRNA synthesis. Thus, polymorphism in the (5A/6A) promoter region of the MMP3 gene results in different transcriptional activities and is related to susceptibility in diseases. The aim of the present study was to detect polymorphism in the MMP3 gene-promoter region in oral submucous fibrosis patients (OSF), oral squamous cell carcinoma patients (OSCC), and normal individuals with tobacco and areca nut habit and without lesions, and to correlate the genotype as a risk factor in these diseases. METHOD: Genomic DNA from blood of OSF (n = 5), OSCC (n = 5), and normal individuals with tobacco and areca nut habit (n = 5) and without (n = 5) were subjected to polymerase chain reaction of the MMP3 gene-promoter region and DNA sequencing. RESULTS: The 5A allele in the MMP3 gene-promoter region was observed more frequently in the OSF group than the control groups. No significant difference was noted between OSCC and the control groups on the 5A allele. CONCLUSION: The results indicated that the 5A allele of the MMP3 gene-promoter region could be associated with OSF risk factor, but not OSCC, in an Indian population. PMID- 27389716 TI - Venous ulcers and risk of occult hematological or other cancers: a nationwide cohort study. PMID- 27389715 TI - Cooperation of germ line JAK2 mutations E846D and R1063H in hereditary erythrocytosis with megakaryocytic atypia. AB - The role of somatic JAK2 mutations in clonal myeloproliferative neoplasms (MPNs) is well established. Recently, germ line JAK2 mutations were associated with polyclonal hereditary thrombocytosis and triple-negative MPNs. We studied a patient who inherited 2 heterozygous JAK2 mutations, E846D from the mother and R1063H from the father, and exhibited erythrocytosis and megakaryocytic atypia but normal platelet number. Culture of erythroid progenitors from the patient and his parents revealed hypersensitivity to erythropoietin (EPO). Using cellular models, we show that both E846D and R1063H variants lead to constitutive signaling (albeit much weaker than JAK2 V617F), and both weakly hyperactivate JAK2/STAT5 signaling only in the specific context of the EPO receptor (EPOR). JAK2 E846D exhibited slightly stronger effects than JAK2 R1063H and caused prolonged EPO-induced phosphorylation of JAK2/STAT5 via EPOR. We propose that JAK2 E846D predominantly contributes to erythrocytosis, but is not sufficient for the full pathological phenotype to develop. JAK2 R1063H, with very weak effect on JAK2/STAT5 signaling, is necessary to augment JAK2 activity caused by E846D above a threshold level leading to erythrocytosis with megakaryocyte abnormalities. Both mutations were detected in the germ line of rare polycythemia vera, as well as certain leukemia patients, suggesting that they might predispose to hematological malignancy. PMID- 27389717 TI - Biochemical and structural analysis of the interaction between beta-amyloid and fibrinogen. AB - The majority of patients with Alzheimer disease (AD) suffer from impaired cerebral circulation. Accumulating evidence suggests that fibrinogen, the main protein component of blood clots, plays an important role in this circulatory dysfunction in AD. Fibrinogen interacts with beta-amyloid (Abeta), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition is found in the brains of AD patients and mouse models. In this study, we investigated the biochemical and structural details of the Abeta-fibrinogen interaction. We identified the central region of Abeta42 as the most critical region for the interaction, which can be inhibited by specific antibodies against the central region of Abeta and by naturally occurring p3 peptides, Abeta17-40 and Abeta17 42. X-ray crystallographic analysis revealed that Abeta42 binding to fragment D of fibrinogen induced a structural change in the C-terminal region of the fibrinogen beta-chain (beta384-393). Furthermore, we identified an additional Abeta-binding site within the alphaC region of fibrinogen. Abeta binding to this alphaC region blocked plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of a plasmin-resistant fibrin degradation fragment. Overall, our study elucidates the Abeta-fibrinogen interaction and clarifies the mechanism by which Abeta-fibrinogen binding delays fibrinolysis by plasmin. These results may facilitate the development of effective therapeutics against the Abeta-fibrinogen interaction to treat cerebrovascular abnormalities in AD. PMID- 27389719 TI - [Not Available]. PMID- 27389718 TI - Idiopathic eruptive macular pigmentation in a child with citrin deficiency. AB - Idiopathic eruptive macular pigmentation (IEMP) is a rare dermatological disorder with generally unclear etiology and pathogenesis. A 51/2-year-old girl was referred to hospital with a 10 month history of brown skin rashes. In early infancy, citrin deficiency had been diagnosed with the SLC25A13 genotype c.851_854del4/c.998G > A, but all clinical and laboratory abnormalities recovered following the introduction of a lactose-free and medium-chain triglyceride enriched formula. Physical examination at referral indicated symmetric, multiple and non-scaly brown macules on the neck, trunk, buttocks and proximal parts of the extremities. Histopathology indicated epidermal basal layer hyperpigmentation with an irregular distribution, along with a large number of melanophages in the upper dermis. The diagnosis of IEMP was thus made. Within 2 years of follow up, the rashes disappeared spontaneously and gradually. To our knowledge, this is the first description of IEMP in a patient with silent citrin deficiency. PMID- 27389720 TI - A Cross-Lag Panel Analysis of Low Self-Esteem as a Predictor of Adolescent Internalizing Symptoms in a Prospective Longitudinal Study. AB - Self-esteem, generally regarded as an important indicator of adolescents' mental health, was assessed by a self-report questionnaire in a school sample of 593 subjects who had been assessed at 3 time points over 7 years between 11 and 25 years of age within the Zurich Psychology and Psychopathology Study (ZAPPS). Cross-lagged panel analyses of the longitudinal data from ZAPPS indicated that self-esteem was predictive of internalizing problems and had an impact on internalizing symptoms when the analyses were adjusted for coping behavior, efficiency of social networks, and impact of stressful life events. Self-esteem was also stable (r = .37-.60) within the observed age range, after controlling for prior levels of the predicted variables. The findings support the impact of self-esteem on mental health and indicate the importance of addressing self esteem in prevention and intervention programs. PMID- 27389721 TI - Canine parvovirus: the worldwide occurrence of antigenic variants. AB - The most important enteric virus infecting canids is canine parvovirus type 2 (CPV-2). CPV is the aetiologic agent of a contagious disease, mainly characterized by clinical gastroenteritis signs in younger dogs. CPV-2 emerged as a new virus in the late 1970s, which could infect domestic dogs, and became distributed in the global dog population within 2 years. A few years later, the virus's original type was replaced by a new genetic and antigenic variant, called CPV-2a. Around 1984 and 2000, virus variants with the single change to Asp or Glu in the VP2 residue 426 were detected (sometimes termed CPV-2b and -2c). The genetic and antigenic changes in the variants have also been correlated with changes in their host range; in particular, in the ability to replicate in cats and also host range differences in canine and other tissue culture cells. CPV-2 variants have been circulating among wild carnivores and have been well documented in several countries around the world. Here, we have reviewed and summarized the current information about the worldwide distribution and evolution of CPV-2 variants since they emerged, as well as the host ranges they are associated with. PMID- 27389723 TI - From suspected Creutzfeldt-Jakob disease to confirmed histoplasma meningitis. AB - A 77-year-old man with chronic obstructive lung disease who was on steroids, presented to the hospital after a fall with subacute headaches and ataxia. During the patient's hospital course, his clinical condition deteriorated with myoclonic jerks, fevers and severe encephalopathy. An extensive workup, including EEG, brain MRI and lumbar puncture, revealed possible Creutzfeldt-Jakob disease. Unfortunately, the patient failed to improve and died 12 days after admission. A brain-only autopsy revealed he had acute histoplasma meningitis with patchy superficial cerebritis. PMID- 27389722 TI - Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity. AB - We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. PMID- 27389724 TI - Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age. AB - A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life threatening. She had disease progression 9 months into treatment. PMID- 27389725 TI - Recurrent meningioma of the scalp after 13 years. AB - Meningiomas represent some of the most common types of tumour of the central nervous system. They are considered benign, with ~1 in 1000 known to metastasise. We report a case of recurrent meningioma of the scalp 13 years following craniotomy to treat the primary. The recurrent tumour of the scalp was eventually excised 5 years later and the defect closed with an anterolateral thigh free flap in a joint procedure between the neurosurgeons and plastic surgeons. Histology of the scalp lesion confirmed a WHO grade I meningioma. Although a number of explanations for recurrent scalp meningiomas exist, the precise role of isolated genetic defects in scalp meningiomas is incomplete. The scalp meningioma in this case consisted of a complex karyotype suggestive of more aggressive disease. This case emphasises that cytogenetics may play a greater role in identifying more aggressive tumours than histology alone. PMID- 27389726 TI - Dermatofibrosarcoma protuberans of the scalp, with fibrosarcomatous areas masquerading as epidermal inclusion cyst. AB - Lesions on the scalp are frequently encountered in clinical practice. Commonly diagnosed lesions include epidermal inclusion cysts (EICs), dermoid cysts and lipomas. Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant skin tumour occurring mostly in the extremities. However, its occurrence on the scalp is unusual, with an incidence of <5%. This lesion is rarely known to undergo fibrosarcomatous transformation. We present two such rare cases of DFSP of the scalp, with fibrosarcomatous transformation, masquerading clinically as EIC. PMID- 27389727 TI - Pericardial effusion with Mycobacterium avium complex in HIV-infected patients. AB - Disseminated atypical Mycobacterium infection is a well-known opportunistic infection in HIV-infected patients with advanced immune deficiency before the introduction of combination antiretroviral therapy. Although the disseminated infection is now rare, few cases of localised infections are reported. A 38-year old man was diagnosed with HIV infection during asymptomatic sexual health screening. Although he was asymptomatic on diagnosis, he had advanced immunodeficiency; therefore, combination antiretroviral therapy was started immediately. After 5 months of treatment, he developed pericardial effusion. Mycobacterium was detected from a culture of the pericardial fluid and Mycobacterium avium complex was identified using a gene probe test. He was treated with combination therapy for Mycobacterium infection and he fully recovered. Treatment continued for 4 years until he achieved adequate immune recovery. PMID- 27389728 TI - Penicillin-induced liver injury during treatment for ocular neurosyphilis. AB - A 51-year-old man, homosexual, recently diagnosed with ocular neurosyphilis, presented to the emergency room with a 1-day history of fevers and chills. His vital signs were significant for a temperature of 102.8 degrees F and tachycardia of 125 bpm. The patient had experienced blurred vision in his left eye and was diagnosed with ocular neurosyphilis 10 days prior to the current presentation. He was treated with a 14-day course of high-dose intravenous penicillin and oral prednisone. His laboratory studies were significant for transaminitis, with an aspartate aminotransferase of 1826 U/L, alanine aminotransferase of 1743 U/L, total bilirubin of 1.2 mg/dL and alkaline phosphatase of 68 U/L. After ruling out viral aetiologies and toxin-induced hepatic injury, penicillin was discontinued on the day following admission and transaminases promptly improved with resolution of symptoms. The patient's vision returned to normal within 2 weeks after discharge from hospital. PMID- 27389729 TI - Direct transatrial pericardiocentesis for tamponade caused by left atrial perforation after trans-septal puncture. AB - Trans-septal puncture is associated with risks of serious complications. We report a case of an obese 52-year-old man with hypertrophic cardiomyopathy who underwent preoperative coronary angiography and cardiac catheterisation complicated by left atrial perforation. We describe a direct transatrial pericardiocentesis approach to treating cardiac tamponade. PMID- 27389730 TI - Classical triad of Kearns-Sayre syndrome. PMID- 27389731 TI - Distal coronary embolisation during transcatheter aortic valve implantation. AB - A 92-year-old woman was admitted to a hospital with severe aortic valve stenosis for transcatheter aortic valve implantation (TAVI). TAVI was performed under general anaesthesia. After balloon valvuloplasty, the patient became hypotensive and transesophageal echocardiography showed severe aortic regurgitation with severely depressed left ventricular wall motion. A 26 mm Sapien XT valve was deployed. However, the ventricular wall motion was still severely depressed. Coronary angiography showed occlusion of the mid-left anterior descending (LAD) artery. After crossing a 0.014" guidewire, manual vacuum aspiration was conducted and multiple emboli were removed. 2 drug-eluting stents were deployed in the LAD artery. Following this, the left ventricular wall motion improved. The patient's failure symptoms improved remarkably after TAVI. Histopathological examination of the aspirated emboli was compatible with a recent thrombus containing platelets, fibrin, erythrocytes and leucocytes. This is the first report to describe a distal coronary embolisation during TAVI with histopathological confirmation of the embolus. PMID- 27389732 TI - Supramolecular Chirality: Vesicle-to-Chiral Helix Transition of the Micelles Consisting of a Sugar-Bearing Calix[4]arene Surfactant. AB - Supramolecular self-assembly and the resulting chiral transfer from the molecular level to the nanoscale is a major topic in modern supramolecular chemistry. We synthesized a galactose-bearing calix[4]arene surfactant (chiral) and mixed it with a primary amine-bearing analogue (achiral). The mixture showed strong induced circular dichroism (ICD) at an almost 3:2 molar ratio of the two surfactants, and exothermic heat was observed upon mixing. The magnitude of DeltaH was comparable to that of van der Waals interactions. This phenomenon indicated that the ICD can be ascribed to the formation of a new supramolecular assembly in which the stoichiometric interaction between the two molecules leads to complexation and the resultant complex has chiral morphology. Transmission electron microscopy and small-angle X-ray scattering showed that the galactose bearing surfactant forms vesicles, and the mixing induces a transition from the vesicles to threadlike cylinders with a diameter of ~3.0 nm. We presume that these cylinder are twisted because of chiral transfer from the chiral galactose moiety and show ICD. PMID- 27389748 TI - Preventing aggressive behaviour in dogs. AB - Delegates from around the world met at the University of Lincoln on June 11 and 12 for the third annual UK Dog Bite Prevention and Behaviour conference. The conference, hosted by dog trainer Victoria Stilwell, brings together dog behaviour experts to discuss possible solutions to this public health issue. Rachel Orritt, who has been examining the perceptions, assessment and management of human-directed aggressive behaviour in dogs for her PhD, reports. PMID- 27389734 TI - Morphology, seasonality and phylogeny of Zschokkella trachini n. sp. (Myxozoa, Myxosporea) infecting the gallbladder of greater weever Trachinus draco (L.) from Tunisian waters. AB - We describe a new myxosporean species, Zschokkella trachini n. sp., infecting the gallbladder of greater weever Trachinus draco Linnaeus 1758 from Tunisia. This is the first record of Zschokkella species in T. draco. Plasmodia were polysporic producing six to eight mature spores; they were attached to the gallbladder epithelium or free floating in the bile. Mature spores were sub-ovoid in the frontal view, measured 15.2 +/- 0.6 (14.4-16.0) MUm in length and 9.8 +/- 0.7 (9.0-10.8) MUm in width. Two equal spherical polar capsules 4.0 +/- 0.4 (3.6-4.5) MUm in diameter, were located separately at the spore's extremities. The prevalence of infection ranged from 23.5 to 87.7 %. Morphological data and molecular analysis of the small subunit rDNA gene identified this parasite as a new species of Zschokkella. Neighbour joining clustered the parasite in a sub clade containing other Zschokkella species parasiting the gallbladder of marine fish hosts, located within the coelozoic clade of the major freshwater clade. This is the second Zschokkella species reported from Tunisia. PMID- 27389749 TI - Cats: their history and our evolving relationship with them. AB - Cats have had a long relationship with people, and their history as a domesticated animal can be traced back as far as 2000 BC. Delegates at a recent conference titled 'People, cats and vets through history' delved a little deeper into the changing nature of this relationship. Georgina Mills reports. PMID- 27389733 TI - Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development. AB - Cilia arose early during eukaryotic evolution, and their structural components are highly conserved from the simplest protists to complex metazoan species. In recent years, the role of cilia in the ontogeny of vertebrate organs has received increasing attention due to a staggering correlation between human disease and dysfunctional cilia. In particular, the presence of cilia in both the developing and mature kidney has become a deep area of research due to ciliopathies common to the kidney, such as polycystic kidney disease (PKD). Interestingly, mutations in genes encoding proteins that localize to the cilia cause similar cystic phenotypes in kidneys of various vertebrates, suggesting an essential role for cilia in kidney organogenesis and homeostasis as well. Importantly, the genes so far identified in kidney disease have conserved functions across species, whose kidneys include both primary and motile cilia. Here, we aim to provide a comprehensive description of cilia and their role in kidney development, as well as highlight the usefulness of the zebrafish embryonic kidney as a model to further understand the function of cilia in kidney health. PMID- 27389750 TI - Companion animal medicine: fresh challenges in the evidence-based, client-focused fast lane. AB - In the last of Veterinary Record's series of articles on the state of different sectors of the veterinary profession, Ross Allan reflects on some of the forces driving companion animal medicine forward. PMID- 27389751 TI - Failure of maternal colostral antibody transfer in lambs linked to excess dietary iodine. AB - Failure of maternal colostral antibody transfer in lambsHypomagnesaemia in calvesHyperplastic goitre in a stillborn calfAbortion storm in a beef herd due to Salmonella MontevideoRickets in hogg lambsStaphylococcus hyicus isolated from piglets with joint ill These are among matters discussed in the disease surveillance report for March 2016 from SAC Consulting: Veterinary Services (SAC C VS). PMID- 27389752 TI - Colostrum in neonatal calves: the key to survival, health and performance. PMID- 27389753 TI - Canine parvovirus study. PMID- 27389754 TI - Transmission of antimicrobial resistance from animals to people. PMID- 27389755 TI - Case of canine ocular thelaziosis in the UK. PMID- 27389756 TI - Photography project. PMID- 27389764 TI - My year as a Fulbrighter. AB - In August 2015 Kate Chandler left London to embark on a masters degree in global policymaking as a Fulbright Scholar, studying first at New York University and then at University College London. As her year as a scholar draws to a close, Kate took time out from working on her dissertation to write for Vet Record Careers. PMID- 27389765 TI - Giant occipital meningohydroencephalocele in an adult: Another historical case in neural tube defects. AB - Meningohydroencephalocele is a herniation of meninges, cerebrospinal fluid, brain parenchyma and a part of the ventricular system through a bony defect in the skull. This bone defect may be congenital, spontaneous or traumatic in origin. The lesions are mostly congenital, discovered generally after birth or in very young infants. We report the first historical case of the entity in this location in a 29-year-old man and discuss the pathogenesis, surgical management and social considerations of this type of neural tube defect in our country. PMID- 27389766 TI - Prologue. PMID- 27389767 TI - Recommendations of the Spanish Society of Pneumology and Thoracic Surgery on the diagnosis and treatment of non-small-cell lung cancer. PMID- 27389769 TI - The policy on sharing data. PMID- 27389768 TI - Exome Array Analysis of Susceptibility to Pneumococcal Meningitis. AB - Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 * 10(-7)). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 * 10(-6); G allele OR 3.21 [95% CI 2.05-5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 * 10(-5); G allele OR 0.66 [95% CI 0.54-0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 * 10(-7)). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID- 27389770 TI - Microaneurysms cause refractory macular edema in branch retinal vein occlusion. AB - Intravitreal anti-vascular endothelial growth factor (VEGF) agents can treat macular edema (ME) in branch retinal vein occlusion (BRVO). However, refractory ME, the mechanism of which is not well elucidated, occurs frequently. Sixty-six eyes with ME secondary to BRVO were enrolled in this retrospective observational case-control study. Twenty eyes received a sub-Tenon's capsule injection of triamcinolone acetonide (STTA), 22 eyes an intravitreal anti-VEGF injection (ranibizumab), 16 eyes were switched from STTA to ranibizumab, 4 eyes underwent vitrectomy, and 4 eyes were untreated. Multiple regression analysis and multivariate logistic regression analysis were conducted, respectively, to identify independent predictors of visual acuity (VA) prognosis and risk factors for refractory ME longer than 1 year. The mechanism of refractory ME and therapeutic approaches for identified risk factors also were investigated. Thirty four (52%) eyes had refractory ME for over 1 year. Microaneurysms were identified as risk factors for refractory ME, leading to poor final VA. Ranibizumab suppressed microaneurysm formation and refractory ME, with early administration more effective. For already formed microaneurysms, laser photocoagulation reduced additional treatments. Microaneurysms may cause refractory ME in BRVO. Alternative therapy to suppress microaneurysms should be considered to prevent refractory ME in patients with BRVO. PMID- 27389771 TI - Cytoplasmic localization of SBR (Dm NXF1) protein and its zonal distribution in the ganglia of Drosophila melanogaster larvae. AB - The Drosophila gene Dm nxf1 (nuclear export factor 1) previously known as small bristles (sbr) controls nuclear export of various mRNA transcripts. We found that Dm NXF1 is present not only in nucleoplasm or at the nuclear rim but also in the cytoplasm. On the spatiotemporal level, anti-SBR antibodies labeled some neuroblasts and their lineages in the brains of Drosophila larvae. The number of Dm NXF1-rich lineages increased during larval development, but Dm NXF1 expression was not evident in all lineages. In all larval stages, Dm NXF1 concentrated in the midline cells of the ventral nerve cord, which reflects a specific status of those cells. In neurites, Dm NXF1 was present in the form of cytoplasmic granules, which is similar to the behavior of another RNA-binding protein, dFMR. Interestingly, though, the granule expression pattern of Dm NXF1 and dFMR did not always overlap, as some granules stained exclusively for one or the other protein. It suggests the existence of specific mRNA partners for Dm NXF1 in neurites. PMID- 27389772 TI - Predictors of inpatient (neuro)rehabilitation after acute care of severe traumatic brain injury: An epidemiological study. AB - OBJECTIVE: To describe the discharge destination of patients with severe traumatic brain injury (sTBI) after acute care. To identify predictors associated with inpatient rehabilitation (vs discharge home) and to identify predictors associated with neurorehabilitation (vs general rehabilitation). METHODS: A national, multi-centre, prospective study with adult survivors after sTBI (abbreviated injury scale head score > 3). Univariate and multivariate logistic regression models included patient characteristics, pre-injury conditions, initial neuro-physiological assessment, trauma mechanisms, severity of TBI and pre-hospital conditions to find predictors of discharge destination. RESULTS: Out of the 566 included patients, 341 (60%) were referred to inpatient rehabilitation, thereof 249 (73%) to neurorehabilitation; 225 (40%) were discharged home or to a nursing home. Lower scores on the Glasgow Coma Scale at admission/at 14 days, higher injury severity scores and older age were predictors for inpatient rehabilitation. Younger age and male gender were predictors for neurorehabilitation. CONCLUSIONS: Patients' pathways after acute care are not only determined by the severity of their brain injury, but also by their overall injury severity and socio-biological factors. More than half of the patients after sTBI are not discharged to specialized inpatient neurorehabilitation and, therefore, efforts should be taken to optimize post-acute care. PMID- 27389773 TI - Expanding the repertoire of L-DOPA's actions: A comprehensive review of its functional neurochemistry. AB - Though a multi-facetted disorder, Parkinson's disease is prototypically characterized by neurodegeneration of nigrostriatal dopaminergic neurons of the substantia nigra pars compacta, leading to a severe disruption of motor function. Accordingly, L-DOPA, the metabolic precursor of dopamine (DA), is well established as a treatment for the motor deficits of Parkinson's disease despite long-term complications such as dyskinesia and psychiatric side-effects. Paradoxically, however, despite the traditional assumption that L-DOPA is transformed in residual striatal dopaminergic neurons into DA, the mechanism of action of L-DOPA is neither simple nor entirely clear. Herein, focussing on its influence upon extracellular DA and other neuromodulators in intact animals and experimental models of Parkinson's disease, we highlight effects other than striatal generation of DA in the functional profile of L-DOPA. While not excluding a minor role for glial cells, L-DOPA is principally transformed into DA in neurons yet, interestingly, with a more important role for serotonergic than dopaminergic projections. Moreover, in addition to the striatum, L-DOPA evokes marked increases in extracellular DA in frontal cortex, nucleus accumbens, the subthalamic nucleus and additional extra-striatal regions. In considering its functional profile, it is also important to bear in mind the marked (probably indirect) influence of L-DOPA upon cholinergic, GABAergic and glutamatergic neurons in the basal ganglia and/or cortex, while anomalous serotonergic transmission is incriminated in the emergence of L-DOPA elicited dyskinesia and psychosis. Finally, L-DOPA may exert intrinsic receptor-mediated actions independently of DA neurotransmission and can be processed into bioactive metabolites. In conclusion, L-DOPA exerts a surprisingly complex pattern of neurochemical effects of much greater scope that mere striatal transformation into DA in spared dopaminergic neurons. Their further experimental and clinical clarification should help improve both L-DOPA-based and novel strategies for controlling the motor and other symptoms of Parkinson's disease. PMID- 27389774 TI - Protective Role of Quercetin in Cadmium-Induced Cholinergic Dysfunctions in Rat Brain by Modulating Mitochondrial Integrity and MAP Kinase Signaling. AB - With the increasing evidences of cadmium-induced cognitive deficits associated with brain cholinergic dysfunctions, the present study aimed to decipher molecular mechanisms involved in the neuroprotective efficacy of quercetin in rats. A decrease in the binding of cholinergic-muscarinic receptors and mRNA expression of cholinergic receptor genes (M1, M2, and M4) was observed in the frontal cortex and hippocampus on exposure of rats to cadmium (5.0 mg/kg body weight, p.o.) for 28 days compared to controls. Cadmium exposure resulted to decrease mRNA and protein expressions of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) and enhance reactive oxygen species (ROS) generation associated with mitochondrial dysfunctions, ultrastructural changes, and learning deficits. Enhanced apoptosis, as evidenced by alterations in key proteins involved in the pro- and anti-apoptotic pathway and mitogen-activated protein (MAP) kinase signaling, was evident on cadmium exposure. Simultaneous treatment with quercetin (25 mg/kg body weight, p.o.) resulted to protect cadmium-induced alterations in cholinergic-muscarinic receptors, mRNA expression of genes (M1, M2, and M4), and expression of ChAT and AChE. The protective effect on brain cholinergic targets was attributed to the antioxidant potential of quercetin, which reduced ROS generation and protected mitochondrial integrity by modulating proteins involved in apoptosis and MAP kinase signaling. The results exhibit that quercetin may modulate molecular targets involved in brain cholinergic signaling and attenuate cadmium neurotoxicity. PMID- 27389775 TI - Astrocytes Can Adopt Endothelial Cell Fates in a p53-Dependent Manner. AB - Astrocytes respond to a variety of CNS injuries by cellular enlargement, process outgrowth, and upregulation of extracellular matrix proteins that function to prevent expansion of the injured region. This astrocytic response, though critical to the acute injury response, results in the formation of a glial scar that inhibits neural repair. Scar-forming cells (fibroblasts) in the heart can undergo mesenchymal-endothelial transition into endothelial cell fates following cardiac injury in a process dependent on p53 that can be modulated to augment cardiac repair. Here, we sought to determine whether astrocytes, as the primary scar-forming cell of the CNS, are able to undergo a similar cellular phenotypic transition and adopt endothelial cell fates. Serum deprivation of differentiated astrocytes resulted in a change in cellular morphology and upregulation of endothelial cell marker genes. In a tube formation assay, serum-deprived astrocytes showed a substantial increase in vessel-like morphology that was comparable to human umbilical vein endothelial cells and dependent on p53. RNA sequencing of serum-deprived astrocytes demonstrated an expression profile that mimicked an endothelial rather than astrocyte transcriptome and identified p53 and angiogenic pathways as specifically upregulated. Inhibition of p53 with genetic or pharmacologic strategies inhibited astrocyte-endothelial transition. Astrocyte-endothelial cell transition could also be modulated by miR-194, a microRNA downstream of p53 that affects expression of genes regulating angiogenesis. Together, these studies demonstrate that differentiated astrocytes retain a stimulus-dependent mechanism for cellular transition into an endothelial phenotype that may modulate formation of the glial scar and promote injury induced angiogenesis. PMID- 27389776 TI - Tanshinone I Induces Mitochondrial Protection through an Nrf2-Dependent Mechanism in Paraquat-TreatedHuman Neuroblastoma SH-SY5Y Cells. AB - Tanshinone I (T-I; 1,6-Dimethylnaphtho[1,2-g][1]benzofuran-10,11-dione; C18H12O3), which may be found in Salvia miltiorrhiza Bunge (Danshen), is a potent anti-inflammatory, antioxidant, and anti-cancer agent. At least in part, T-I exerts antioxidant activity by activating signaling pathways associated with the maintenance of the redox state in mammalian cells. In this context, the upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has received attention regarding the role of this transcription factor in modulating the expression of antioxidant enzymes and the metabolism of glutathione (GSH). Even though there is a growing body of evidence suggesting that T-I mediates protection against several pro-oxidant challenges in both in vitro and in vivo experimental models, it remains to be examined whether and how T-I would modulate mitochondrial function during redox disturbances. Therefore, we aimed to reveal whether T-I would exhibit protective effects on mitochondria of SH-SY5Y cells treated with paraquat (PQ), a well-known mitochondrial toxic agent. We found that T-I pretreatment significantly protected mitochondria against PQ-induced redox impairment through an Nrf2-dependent mechanism involving upregulation of antioxidant enzymes, such as Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and both catalytic and modifier subunits of gamma-glutamate cysteine ligase (gamma-GCL). T-I prevented complex I and mitochondrial membrane potential (MMP) impairments elicited by PQ. Thus, T-I may be viewed as a new mitochondrial protective agent whose complete mechanism of action needs to be investigated, but it seems to involve mitochondriotropic aspects related to the chemistry of this molecule. PMID- 27389777 TI - Noggin Along with a Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Tyrosine Hydroxylase Gene Expression. AB - Tyrosine hydroxylase (TH), a rate-limiting step in catecholamine synthesis in which its activity influences Alzheimer disease, Parkinson disease, and IQ of schizophrenia patients, has been studied for a long time. In the meantime, the present investigation assessed the effect of noggin and type of self-assembling nanofibers in TH gene over-expression by neuron-like cells derived from human endometrial-derived stromal cells (hEnSCs). Neuroblastoma cells and hEnSCs encapsulated into nanofibers including Matrigel, (RADA)4, laminin, and BMHP-1 motif bounded to (RADA)4 and their cell viability were studied for 48 h and 18 days in basal and neurogenic media, respectively, in noggin-rich media. Then, expression of neural genes and proteins has been investigated by immunocytochemistry (ICC) and real-time PCR methods, respectively. The results indicated that neuroblastoma cell and hEnSC viability is in good agreement with the level of Bcl2 and beta-tubulin III gene expression; however, -BMHP-1 and laminin nanofibers exhibited significantly higher cell viability eventually through Wnt/beta-catenin signaling pathway as compared to others, respectively. The gene expression analysis of nanofibers showed that none of them induced gamma aminobutyric acid (GABA) gene expression while glial fibrillary acidic protein (GFAP) gene just over-expressed in cells encapsulated into Matrigel with a low level of Bcl2 gene expression. However, the TH gene just had been over-expressed in cells encapsulated into -laminin nanofiber and 2D cell culture. In the absence of noggin with -laminin nanofibers, TH gene expression was suppressed. It might be concluded that although noggin through anti-BMP pathways resulted in GFAP decrement and TH gene increment, the type of scaffold that defined the final fate of cells and -laminin accompaniment might be useful for the recovery of Alzheimer and Parkinson disease patients. PMID- 27389778 TI - A novel measure of poverty and its association with elevated sexual risk behavior among young Black MSM. AB - This study determined whether a novel (single-item) measure of poverty is associated with elevated sexual risk among young Black men who have sex with men who reside in a US city with high HIV seroprevalence. A convenience sample of 600 Black men who have sex with men (ages 16-29) completed a computer-assisted self interview. The questionnaire included an item asking men, 'In the past 12 months have you missed meals because you did not have enough money to eat?' Selected measures of sexual risk and prevalence of chlamydia, gonorrhea, and HIV were assessed as outcomes of this novel measure of poverty. About 22% had missed meals due to lack of money. In age-adjusted analyses, these men were more likely to report: (1) having concurrent sex partners ( P = .03), (2) having sex with partners who were generally five or more years older ( P = .02), (3) not using condoms the first time they had sex with their most recent new partner ( P = .015), (4) having sex with persons not known by name ( P = .02), (5) depending on sex partners for food, money, and shelter ( P < .0001), and (6) testing positive for Chlamydia at study enrollment ( P < .02). Of interest, an association in frequency of recent condomless anal sex as top ( P = .04) was observed; however, the association for recent condomless sex as bottom ( P = .37) was not significant. For young Black men who have sex with men, a novel method of assessing poverty may be predictive of many sexual risk behaviors. Clinicians may benefit this population by including this question as part of their patient interview and prioritizing services when indicated. PMID- 27389779 TI - De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia. AB - BACKGROUND: The causes of intellectual disability (ID) are diverse and de novo mutations are increasingly recognised to account for a significant proportion of ID. METHODS AND RESULTS: In this study, we performed whole exome sequencing on a large cohort of patients with ID or neurodevelopmental delay and identified four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. HECW2 is an ubiquitin ligase that stabilises p73, a crucial mediator of neurodevelopment and neurogenesis. CONCLUSION: This study implicates pathogenic genetic variants in HECW2 as potential causes of neurodevelopmental disorders in humans. PMID- 27389780 TI - Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection. AB - The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes' equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called 'prototypic' and 'arkypallidal' neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID- 27389781 TI - Laboratory Response to Ebola - West Africa and United States. AB - The 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa highlighted the need to maintain organized laboratory systems or networks that can be effectively reorganized to implement new diagnostic strategies and laboratory services in response to large-scale events. Although previous Ebola outbreaks enabled establishment of critical laboratory practice safeguards and diagnostic procedures, this Ebola outbreak in West Africa highlighted the need for planning and preparedness activities that are better adapted to emerging pathogens or to pathogens that have attracted little commercial interest. The crisis underscored the need for better mechanisms to streamline development and evaluation of new diagnostic assays, transfer of material and specimens between countries and organizations, and improved processes for rapidly deploying health workers with specific laboratory expertise. The challenges and events of the outbreak forced laboratorians to examine not only the comprehensive capacities of existing national laboratory systems to recognize and respond to events, but also their sustainability over time and the mechanisms that need to be pre-established to ensure effective response. Critical to this assessment was the recognition of how response activities (i.e., infrastructure support, logistics, and workforce supplementation) can be used or repurposed to support the strengthening of national laboratory systems during the postevent transition to capacity building and recovery. This report compares CDC's domestic and international laboratory response engagements and lessons learned that can improve future responses in support of the International Health Regulations and Global Health Security Agenda initiatives.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27389783 TI - Future Papers. PMID- 27389782 TI - Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis. AB - Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation. PMID- 27389784 TI - Cytotoxic and Apoptosis-inducing Activities of Taraxastane-type Triterpenoid Derivatives in Human Cancer Cell Lines. AB - Twenty-eight taraxastane-type triterpenoid derivatives 4 - 31 were prepared from the naturally occurring triterpenoids faradiol (1) and heliantriol C (3). The cytotoxic activities of these compounds and arnidiol (2) were evaluated in leukemia (HL60), lung (A549), duodenal (AZ521), and breast (SK-BR-3) cancer cell lines. 21-Oxoarnidiol (18) and faradiol 3,16-di-O-l-alaninate (31) exhibited potent cytotoxicity, with 50% inhibitory concentrations of 0.5 - 2.7 MUm. In particular, flow cytometric analysis indicated that compound 31 induced typical apoptotic cell death in HL60 cells. These results suggested that taraxastane-type triterpenoid derivatives might provide useful antitumor agents with apoptosis inducing activity. PMID- 27389785 TI - The application of the comet assay to assess the genotoxicity of environmental pollutants in the nematode Caenorhabditis elegans. AB - This study aimed to establish a protocol for cell dissociation from the nematode Caenorhabditis elegans (C. elegans) to assess the genotoxicity of the environmental pollutant benzo[a]pyrene (BaP) using the alkaline version of the single cell electrophoresis assay (comet assay). BaP genotoxicity was assessed in C. elegans (wild-type [WT]; N2, Bristol) after 48h exposure (0-40MUM). Induction of comets by BaP was concentration-dependent up to 20MUM; comet% tail DNA was ~30% at 20MUM BaP and ~10% in controls. Similarly, BaP-induced DNA damage was evaluated in C. elegans mutant strains deficient in DNA repair. In xpa-1 and apn 1 mutants BaP-induced comet formation was diminished to WT background levels suggesting that the damage formed by BaP that is detected in the comet assay is not recognised in cells deficient in nucleotide and base excision repair, respectively. In summary, our study provides a protocol to evaluate DNA damage of environmental pollutants in whole nematodes using the comet assay. PMID- 27389786 TI - The Evolving and Future Role of Taxanes in Squamous Cell Carcinomas of the Head and Neck: A Review. AB - IMPORTANCE: Since their discovery in the 1970s, taxanes have maintained widespread clinical use in solid tumors, including squamous cell carcinoma of the head and neck (SCCHN), but SCCHN remains a difficult malignancy to treat, often requiring a multidisciplinary approach involving surgery, radiotherapy, and chemotherapy. Taxanes have been heavily studied in the treatment of SCCHN, and their use is currently in the setting of induction chemotherapy with the TPF (docetaxel, FU, cisplatin) regimen for locally advanced SCCHN, as well as in the concurrent therapy setting. However, there is still no clear guideline or indication for the use of taxanes in SCCHN. OBSERVATIONS: A literature search was completed in PubMed using the search terms "taxane," "head and neck cancer," "docetaxel," "paclitaxel," and "chemotherapy," for articles published between 1990 to 2015. In this review, we provide an overview of the evidence thus far supporting the use of taxanes in the concurrent, induction, and adjuvant settings, as well as their use in the treatment of recurrent or metastatic SCCHN. For locally advanced disease, docetaxel is part of the first line regimen for induction therapy, although the superiority of sequential therapy compared with concurrent therapy is still in question. In addition, several studies have shown at least equivalent outcomes for regimens including taxanes compared with standard platinum-based regimens. In the adjuvant setting, RTOG (Radiation Therapy Oncology Group) 1216 is looking into the prospect of docetaxel as a first line agent for systemic therapy following surgery. In metastatic disease, various second-line regimens include taxanes, and their use is being considered in first line therapies as well. Several phase 3 trials involving taxanes are underway, with the possibility that they will provide results that increase taxane use in SCCHN. In addition to reviewing their current use, we also provide an analytical discussion of the projected future role of taxanes in the management of SCCHN. Ongoing and future studies involving taxanes are also discussed. CONCLUSIONS AND RELEVANCE: While the current role of taxane use in SCCHN remains to be established, ongoing and future studies involving taxanes will hopefully solidify their role in the treatment of SCCHN. The future role of taxanes will also be influenced by the introduction of novel taxanes, as well as immunotherapy in the treatment of SCCHN. PMID- 27389788 TI - Common modulation of limbic network activation underlies musical emotions as they unfold. AB - Music is a powerful means for communicating emotions among individuals. Here we reveal that this continuous stream of affective information is commonly represented in the brains of different listeners and that particular musical attributes mediate this link. We examined participants' brain responses to two naturalistic musical pieces using functional Magnetic Resonance imaging (fMRI). Following scanning, as participants listened to the musical pieces for a second time, they continuously indicated their emotional experience on scales of valence and arousal. These continuous reports were used along with a detailed annotation of the musical features, to predict a novel index of Dynamic Common Activation (DCA) derived from ten large-scale data-driven functional networks. We found an association between the unfolding music-induced emotionality and the DCA modulation within a vast network of limbic regions. The limbic-DCA modulation further corresponded with continuous changes in two temporal musical features: beat-strength and tempo. Remarkably, this "collective limbic sensitivity" to temporal features was found to mediate the link between limbic-DCA and the reported emotionality. An additional association with the emotional experience was found in a left fronto-parietal network, but only among a sub-group of participants with a high level of musical experience (>5years). These findings may indicate two processing-levels underlying the unfolding of common music emotionality; (1) a widely shared core-affective process that is confined to a limbic network and mediated by temporal regularities in music and (2) an experience based process that is rooted in a left fronto-parietal network that may involve functioning of the 'mirror-neuron system'. PMID- 27389787 TI - Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications. AB - BACKGROUND: Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors. OBJECTIVE: In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly. METHODS: A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review. RESULTS: We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2). DISCUSSION: Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes. CONCLUSIONS: The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex relationship between bipolar disorder and diabetes mellitus could lead to novel therapeutic approaches and improved outcomes. PMID- 27389789 TI - Eyetracker-based gaze correction for robust mapping of population receptive fields. AB - Functional MRI enables the acquisition of a retinotopic map that relates regions of the visual field to neural populations in the visual cortex. During such a "population receptive field" (PRF) experiment, stable gaze fixation is of utmost importance in order to correctly link the presented stimulus patterns to stimulated retinal regions and the resulting Blood Oxygen Level Dependent (BOLD) response of the appropriate region within the visual cortex. A method is described that compensates for unstable gaze fixation by recording gaze position via an eyetracker and subsequently modifies the input stimulus underlying the PRF analysis according to the eyetracking measures. Here we show that PRF maps greatly improve when the method is applied to data acquired with either saccadic or smooth eye movements. We conclude that the technique presented herein is useful for studies involving subjects with unstable gaze fixation, particularly elderly patient populations. PMID- 27389791 TI - Insomnia and depression impair oral health-related quality of life in the old old. AB - AIM: A previous study reported that the oral health-related quality of life (OHRQoL) of Japanese individuals dropped sharply as they reached old-old age. The aim of present study was to explore the risk factors of OHRQoL by investigating the association of OHRQoL with oral indices, lifestyle and psychological distress. METHODS: A questionnaire survey was carried out to assess the OHRQoL, oral indices, lifestyle, and psychological distress of patients who were of >=75 years of age and who regularly visited a dental clinic for maintenance. OHRQoL and psychological distress were assessed using the General Oral Health Assessment Index (GOHAI) and the General Health Questionnaire, respectively. The relationships between the GOHAI score and related factors were examined by non parametric bivariate and logistic regression analyses using a GOHAI cut-off score of 45.0. RESULTS: A total of 187 old-old patients with a mean age of 77.9 +/- 3.0 years participated in the present study. The average GOHAI score was 50.8 +/- 8.0. In the bivariate analyses, the average sleeping hours, use of sleep medication, Short Form 8-Item Health Survey (SF-8), General Health Questionnaire score, and the number of teeth present were significantly correlated with the GOHAI score. A logistic regression analysis showed that the number of teeth present, General Health Questionnaire and the use of sleep medication were associated with the GOHAI score. CONCLUSIONS: The present study found that the OHRQoL was strongly associated with insomnia and depression. It is therefore suggested that oral healthcare professionals take general background information, such as the presence of insomnia and depression, into consideration to improve OHRQoL when they treat old-old patients. Geriatr Gerontol Int 2017; 17: 893-897. PMID- 27389790 TI - Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain. AB - Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d-MRI) analyses, such as neurite density and diffusion kurtosis imaging (DKI), are able to capture microstructural changes and are considered to be robust tools in preclinical and clinical imaging. The present study utilized d-MRI analyzed with a neurite density model and the DKI framework to investigate microstructure in the hippocampus, prefrontal cortex, caudate putamen and amygdala regions of CMS rat brains by comparison to brains from normal controls. To validate findings of CMS induced microstructural alteration, histology was performed to determine neurite, nuclear and astrocyte density. d-MRI based neurite density and tensor-based mean kurtosis (MKT) were significantly higher, while mean diffusivity (MD), extracellular diffusivity (Deff) and intra-neurite diffusivity(DL) were significantly lower in the amygdala of CMS rat brains. Deff was also significantly lower in the hippocampus and caudate putamen in stressed groups. Histological neurite density corroborated the d-MRI findings in the amygdala and reductions in nuclear and astrocyte density further buttressed the d-MRI results. The present study demonstrated that the d-MRI based neurite density and MKT can reveal specific microstructural changes in CMS rat brains and these parameters might have value in clinical diagnosis of depression and for evaluation of treatment efficacy. PMID- 27389792 TI - Impact of Employee Assistance Services on Depression, Anxiety, and Risky Alcohol Use: A Quasi-Experimental Study. AB - OBJECTIVE: To test the impact of Employee Assistance Programs (EAPs) on reducing employee depression, anxiety, and risky alcohol use, and whether improvements in clinical symptoms lead to improved work outcomes. METHODS: The study used a prospective, quasi-experimental design with propensity score matching. Participants (n = 344) came from 20 areas of state government. EAP (n = 156) and non-EAP (n = 188) employees were matched on baseline demographic, psychosocial, and work-related characteristics that differentiate EAP from non-EAP users. Follow-up surveys were collected 2 to 12 months later (M = 6.0). RESULTS: EAP significantly reduced symptoms of depression and anxiety, but not at-risk alcohol use. EAP reductions in depression and anxiety mediated EAP-based reductions in absenteeism and presenteeism. CONCLUSIONS: EAPs provide easy-to-access work-based services that are effective at improving employee mental health. PMID- 27389793 TI - Multisymptom Illness in Gulf War Veterans: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The aim of this study was to conduct a systematic review and meta analysis of multisymptom illness (MSI) in 1990 to 1991 Gulf/Afghanistan/Iraq War veterans. METHODS: Electronic databases were searched from January 1990, June 2014 for studies on MSI prevalence in Gulf/Afghanistan/Iraq War veterans, based on the Centers for Disease Control and Prevention MSI case definition, and which included a military comparison group. RESULTS: Seven studies were identified among US, UK, and Australian Gulf War veterans; no studies were identified in Afghanistan/Iraq War veterans. MSI prevalence in Gulf War veterans and comparison groups ranged from 26 to 65% and from 12 to 37%, respectively. More recent studies were larger, with improved designs. The pooled odds ratio comparing Gulf War veterans to other military groups was 2.74 (95% confidence interval 2.15 to 3.51). CONCLUSION: The systematic review showed that MSI was most prevalent in Gulf War veterans, emphasizing the health burden of MSI in this veteran population. PMID- 27389796 TI - Effect of Changing Work Stressors and Coping Resources on Psychological Distress. AB - OBJECTIVES: We examined whether or not changing work stressors and coping resources affect the risk of psychological distress. METHOD: A baseline evaluation of work stressors and coping resources and mental health was assessed for 4362 petroleum industry workers after 12 years. RESULTS: Increased task and organizational stressors were associated with an elevated risk of psychological distress. Decreased task stressors, increased job control, and increased coping resources were associated with a reduced risk of psychological distress. Increased coping also had a buffering effect on increased work stressors and psychological distress. Gender-specific differences were observed in the factors influencing mental health. CONCLUSIONS: The findings indicated that reducing gender-specific task and organizational stressors, and promoting coping resources at work may help prevent the onset of psychological distress. PMID- 27389797 TI - Prospective Cohort Study of Work Functioning Impairment and Subsequent Absenteeism Among Japanese Workers. AB - OBJECTIVE: This study examined the association of work functioning impairment as measured by work functioning impairment scale (WFun) and subsequent sick leave. METHODS: A prospective cohort study was conducted at a manufacturer in Japan, and 1263 employees participated. Information on sick leave was gathered during an 18 month follow-up period. RESULTS: The hazard ratios (HRs) of long-term sick leave were substantially increased for those with a WFun score greater than 25 (HR = 3.99, P = 0.003). The incidence rate ratios (IRRs) of days of short-term absence gradually increased as scores of WFun increased (IRR = 1.18, P < 0.001 in the subjects with WFun of over 25 comparing with those with WFun of 14 or less). CONCLUSIONS: Assessing work functioning impairment is a useful way of classifying risk for future sick leave among employees. PMID- 27389798 TI - Fatigue and Insufficient Leisure Opportunities in Older Employees. AB - OBJECTIVE: The aim of this study was to investigate the impact of age on fatigue prevalence and the potential recovery effect of leisure opportunities. METHODS: The study was based on the Austrian Health Interview Survey 2006/2007. We investigated data of a subsample of working adults, which consisted of 5018 subjects (51.8% males) aged 35 to 59 years. A logistic regression analysis stratified by gender explored whether age and leisure opportunities predicted prolonged fatigue. RESULTS: Age was not associated with fatigue in females, but older male employees (55 to 59 years) were at a greater risk for fatigue than the reference group (35 to 39 years). Insufficient leisure opportunities increased the odds for fatigue in both genders and all age groups. However, this effect was especially pronounced in male employees aged 55 to 59 years. CONCLUSIONS: These results suggest that older male employees may be in need of more leisure opportunities to recover from work. PMID- 27389799 TI - Men in Rural and Remote Locations: Their Preferences for Worksite Wellness Programs. PMID- 27389801 TI - Thematic knowledge, artifact concepts, and the left posterior temporal lobe: Where action and object semantics converge. AB - Converging evidence supports the existence of functionally and neuroanatomically distinct taxonomic (similarity-based; e.g., hammer-screwdriver) and thematic (event-based; e.g., hammer-nail) semantic systems. Processing of thematic relations between objects has been shown to selectively recruit the left posterior temporoparietal cortex. Similar posterior regions have also been shown to be critical for knowledge of relationships between actions and manipulable human-made objects (artifacts). Based on the hypothesis that thematic relationships for artifacts rely, at least in part, on action relationships, we assessed the prediction that the same regions of the left posterior temporoparietal cortex would be critical for conceptual processing of artifact related actions and thematic relations for artifacts. To test this hypothesis, we evaluated processing of taxonomic and thematic relations for artifacts and natural objects as well as artifact action knowledge (gesture recognition) abilities in a large sample of 48 stroke patients with a range of lesion foci in the left hemisphere. Like control participants, patients identified thematic relations faster than taxonomic relations for artifacts, whereas they identified taxonomic relations faster than thematic relations for natural objects. Moreover, response times (RTs) for identifying thematic relations for artifacts selectively predicted performance in gesture recognition. Whole brain Voxel-based Lesion Symptom Mapping (VLSM) analyses and Region of Interest (ROI) regression analyses further demonstrated that lesions to the left posterior temporal cortex, overlapping with LTO and visual motion area hMT+, were associated both with relatively slower RTs in identifying thematic relations for artifacts and poorer artifact action knowledge in patients. These findings provide novel insights into the functional role of left posterior temporal cortex in thematic knowledge, and suggest that the close association between thematic relations for artifacts and action representations may reflect their common dependence on visual motion and manipulation information. PMID- 27389800 TI - Reading words and other people: A comparison of exception word, familiar face and affect processing in the left and right temporal variants of primary progressive aphasia. AB - Semantic variant primary progressive aphasia (svPPA) typically presents with left hemisphere predominant rostral temporal lobe (rTL) atrophy and the most significant complaints within the language domain. Less frequently, patients present with right-hemisphere predominant temporal atrophy coupled with marked impairments in processing of famous faces and emotions. Few studies have objectively compared these patient groups in both domains and therefore it is unclear to what extent the syndromes overlap. Clinically diagnosed svPPA patients were characterized as left- (n = 21) or right-predominant (n = 12) using imaging and compared along with 14 healthy controls. Regarding language, our primary focus was upon two hallmark features of svPPA; confrontation naming and surface dyslexia. Both groups exhibited naming deficits and surface dyslexia although the impairments were more severe in the left-predominant group. Familiarity judgments on famous faces and affect processing were more profoundly impaired in the right predominant group. Our findings suggest that the two syndromes overlap significantly but that early cases at the tail ends of the continuum constitute a challenge for current clinical criteria. Correlational neuroimaging analyses implicated a mid portion of the left lateral temporal lobe in exception word reading impairments in line with proposals that this region is an interface between phonology and semantic knowledge. PMID- 27389802 TI - Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration. AB - In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas. PMID- 27389804 TI - Tannase-mediated biotransformation assisted separation and purification of theaflavin and epigallocatechin by high speed counter current chromatography and preparative high performance liquid chromatography: A comparative study. AB - A large scale isolation and purification of theaflavin (TF) and epigallocatechin (EGC) has been successfully developed by tannase-mediated biotransformation combining high-speed countercurrent chromatography. After tannase hydrolysis of a commercially available theaflavins extract (TE), the content of TF and EGC in tannase-mediated biotransformation product (TBP) achieved approximately 3 times enrichment. SEM studies revealed smooth tannase biotransformation and the possibility of recovery of the tannase. A single 1.5 hours' HSCCC separation for TF and EGC employing a two-phase solvent system could simultaneously produce 180.8 mg of 97.3% purity TF and 87.5 mg of 97.3% purity EGC. However, a preparative HPLC separation of maximum injection volume containing 120 mg TBP prepared 11.2 mg TF of 94.9% purity and 7.7 mg EGC of 89.9% purity. HSCCC separation demonstrated significant advantages over Prep HPLC in terms of sample loading size, separation time, environmental friendly solvent systems, and the production. PMID- 27389806 TI - Interrogating heterobimetallic co-catalytic responses for the electrocatalytic reduction of CO2 using supramolecular assembly. AB - The use of hydrogen-bonding interactions to direct the non-covalent assembly of a heterobimetallic supramolecular system with Re and Mn bipyridine-based electrocatalysts is reported. Under catalytic conditions, the formation of hydrogen bonds generates a catalyst system which passes ~10% more current than the individual current responses of the respective Re and Mn complexes for the reduction of CO2 to CO and H2O. Infrared spectroelectrochemical studies indicate that the Re and Mn metal centers interact during the reduction mechanism, even forming heterobimetallic bonds under reducing conditions in the absence of substrate. These findings demonstrate that non-covalent assembly is a powerful method for generating new co-catalyst systems with greater reactivity and efficiency for transformations of interest. PMID- 27389803 TI - Convergent evidence for hierarchical prediction networks from human electrocorticography and magnetoencephalography. AB - We propose that sensory inputs are processed in terms of optimised predictions and prediction error signals within hierarchical neurocognitive models. The combination of non-invasive brain imaging and generative network models has provided support for hierarchical frontotemporal interactions in oddball tasks, including recent identification of a temporal expectancy signal acting on prefrontal cortex. However, these studies are limited by the need to invert magnetoencephalographic or electroencephalographic sensor signals to localise activity from cortical 'nodes' in the network, or to infer neural responses from indirect measures such as the fMRI BOLD signal. To overcome this limitation, we examined frontotemporal interactions estimated from direct cortical recordings from two human participants with cortical electrode grids (electrocorticography - ECoG). Their frontotemporal network dynamics were compared to those identified by magnetoencephalography (MEG) in forty healthy adults. All participants performed the same auditory oddball task with standard tones interspersed with five deviant tone types. We normalised post-operative electrode locations to standardised anatomic space, to compare across modalities, and inverted the MEG to cortical sources using the estimated lead field from subject-specific head models. A mismatch negativity signal in frontal and temporal cortex was identified in all subjects. Generative models of the electrocorticographic and magnetoencephalographic data were separately compared using the free-energy estimate of the model evidence. Model comparison confirmed the same critical features of hierarchical frontotemporal networks in each patient as in the group wise MEG analysis. These features included bilateral, feedforward and feedback frontotemporal modulated connectivity, in addition to an asymmetric expectancy driving input on left frontal cortex. The invasive ECoG provides an important step in construct validation of the use of neural generative models of MEG, which in turn enables generalisation to larger populations. Together, they give convergent evidence for the hierarchical interactions in frontotemporal networks for expectation and processing of sensory inputs. PMID- 27389805 TI - Dosing targeted and cytotoxic two-drug combinations: Lessons learned from analysis of 24,326 patients reported 2010 through 2013. AB - Combining agents has the potential to attenuate resistance in metastatic cancer. However, knowledge of appropriate starting doses for novel drug combinations in clinical trials and practice is lacking. Analysis of 372 published studies was used to ascertain safe starting doses for doublets involving a cytotoxic and targeted agent. Phase I-III adult oncology clinical trial publications (January 1, 2010 to December 31, 2013) were identified (PubMed). The dose of drug used in each combination was compared to the single agent recommended dose [FDA approved/recommended phase 2 dose (RP2D)/maximum tolerated dose (MTD)]. Dose percentages were calculated as: (safe dose of drug in combination/dose of drug as single agent at FDA/RP2D/MTD) * 100. Additive dose percentages were the sum of the dose percentage for each drug. A total of 24,326 patients (248 drug combinations) were analyzed. In 38% of studies, both drugs could be administered at 100% of their FDA-approved/RP2D/MTD dose. The lowest safe additive dose percentage was 41% with poly-ADP ribose polymerase (PARP) or histone deacetylase inhibitors as the targeted agents; 82%, in the absence of these agents; and 97%, with an antibody in the combination. If one drug was administered at 100% of the single agent dose, the lowest safe dose percentage for the second drug was 17% (cytotoxic at 100%) or 36% (targeted at 100%) of the FDA-approved/RP2D/MTD dose. The current findings can help inform safe starting doses for novel two-drug combinations (cytotoxic and targeted agents) in the context of clinical trials and practice. PMID- 27389807 TI - Exacerbated cardiac fibrosis induced by beta-adrenergic activation in old mice due to decreased AMPK activity. AB - Senescent hearts exhibit defective responses to beta-adrenergic receptor (beta AR) over-activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in protecting against ageing-associated cardiac remodelling in mice upon beta-AR over-activation. 10-week-old (young) and 18-month-old (old) mice were subcutaneously injected with the beta-AR agonist isoproterenol (ISO; 5 mg/kg). More extensive cardiac fibrosis was found in old mice upon ISO exposure than in young mice. Meanwhile, ISO treatment decreased AMPK activity and increased beta arrestin 1, but not beta-arrestin 2, expression, and the effects of ISO on AMPK and beta-arrestin 1 were greater in old mice than in young mice. Similarly, young AMPKalpha2-knockout (KO) mice showed more extensive cardiac fibrosis upon ISO exposure than that was observed in age-matched wild-type (WT) littermates. The extent of cardiac fibrosis in WT old mice was similar to that in young KO mice. Additionally, AMPK activities were decreased and beta-arrestin 1 expression increased in KO mice. In contrast, the AMPK activator metformin decreased beta arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure. In conclusion, more severe cardiac fibrosis is induced by ISO in old mice than in young mice. A decrease in AMPK activity, which further increases beta-arrestin 1 expression, is the central mechanism underlying the ageing-related cardiac fibrosis induced by ISO. The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon beta-AR over-activation. PMID- 27389808 TI - A novel single cell method to identify the genetic composition at a single nuclear body. AB - Gene loci make specific associations with compartments of the nucleus (e.g. the nuclear envelope, nucleolus, and transcription factories) and this association may determine or reflect a mechanism of genetic control. With current methods, it is not possible to identify sets of genes that converge to form a "gene hub" as there is a reliance on loci-specific probes, or immunoprecipitation of a particular protein from bulk cells. We introduce a method that will allow for the identification of loci contained within the vicinity of a single nuclear body in a single cell. For the first time, we demonstrate that the DNA sequences originating from a single sub-nuclear structure in a single cell targeted by two photon irradiation can be determined, and mapped to a particular locus. Its application to single PML nuclear bodies reveals ontologically related loci that frequently associate with each other and with PML bodies in a population of cells, and a possible nuclear body targeting role for specific transcription factor binding sites. PMID- 27389809 TI - Group 2 PH: Medical Therapy. AB - Pulmonary hypertension (PH) secondary to left heart disease, classified as Group 2, is a widely underestimated target of therapy. Prevention and treatment of initial subclinical stages are not valued as a priority in the management of this chronic disease population, whereas attention is high for PH consequences in patients with advanced heart failure (HF) requiring a left ventricular mechanical assist device or heart transplant candidates. Even so, there is a growing interest toward the evidence of a clinical and prognostic role of PH in the elderly populations and in HF with preserved ejection fraction (HFpEF). Certainly, along with a prevalence definition not yet defined, the search for effective pharmacological approaches that might favorably affect the aging process and the natural history of HFpEF from earlier stages is not an easy task. Pharmacological studies that have tested some traditional pulmonary arterial hypertension approved drugs (i.e., prostanoids and endothelin-1 receptor blockers) primarily in PH and HF with reduced ejection fraction have not been positive, especially because of concomitant side effects, i.e., systemic hypotension, fluid retention and hepatic toxicity. In recent years, interest has moved toward drugs overexpressing the nitric oxide (NO)-cyclic guanosine monophosphate pathway with recent availability of well-tolerated selective pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors and guanylate cyclase stimulators. Single center studies performed with these drugs have shown good tolerability and safety profile providing alternating hemodynamic results mainly because of recruitment of patients at different stages of the pulmonary vascular disease. Nonetheless, the overexpression of NO pathway appears to remain the most solid background for targeting lung microvessel dysfunction and treating RV dysfunction since the earliest stages of the disease. PMID- 27389810 TI - Pulmonary Hypertension in Aortic Stenosis and Mitral Regurgitation: Rest and Exercise Echocardiography Significance. AB - Valvular heart disease is a common cause of increased mean pulmonary artery pressure (PAP). Aortic stenosis and mitral regurgitation are frequently accompanied by pulmonary hypertension (PH), especially when they are severe and symptomatic. In asymptomatic patients, PH is rare, though the exact prevalence is unknown and mainly stems from the severity of the valvular heart disease and the presence of diastolic dysfunction. Exercise echocardiography has recently gained interest in depicting PH. In these asymptomatic patients, exercise PH is observed in about >40%. Either PH at rest (systolic PAP >50 mmHg) or during exercise (systolic PAP >60 mmHg) is a powerful determinant of outcome and is independently associated with reduced survival, regardless of the severity of the underlying valvular pathology. PMID- 27389811 TI - Continuous Production of Janus and Composite Liquid Marbles with Tunable Coverage. AB - We report a simple method for on-demand continuous processing of composite liquid marbles with the aid of a 3D printed slide platform, which offers the potential for engineering novel functional surfaces for the production of combination drug therapies, particle-based barcode biomarkers and smart membranes, among other applications. Unlike other attempts at producing such liquid marbles, this novel technique not only facilitates controllable and reproducible production of the liquid marbles but also allows the selection of different morphologies such as banded, patchy, and Janus structures by controlling the coalescence conditions, with the possibility for tunable symmetric and asymmetric patterns, the latter by varying the particle species partitioning ratio. PMID- 27389812 TI - Corrigendum: Artificial Gauge Field and Topological Phase in a Conventional Two dimensional Electron Gas with Antidot Lattices. PMID- 27389813 TI - The effect of terminal substituents on the electronic properties of rod-shaped [HGaNH]n oligomers. AB - The effect of electron-donating and electron-withdrawing terminal groups on the electronic structure of the rod-shaped X3[HGaNH]nY3 or needle-shaped XGa[HGaNH]nNY oligomers (X, Y = H, CH3, F, CF3; n = 9, 30 and 114) was computationally studied at the B3LYP/SVP level of density functional theory. While the needle-shaped oligomers exhibit moderate variability in the electronic structure upon changing the terminal substituents X and Y, the energy gap of long rod-shaped oligomers varies within 2 eV. For oligomers with n = 114, F3[HGaNH]n(CH3)3 exhibits the largest HOMO-LUMO gap of 2.91 eV, while (CH3)3[HGaNH]nF3 has the smallest gap of 0.94 eV. PMID- 27389814 TI - Integrating clinical and genetic observations in facioscapulohumeral muscular dystrophy. AB - PURPOSE OF REVIEW: This review gives an overview of the currently known key clinical and (epi)genetic aspects of facioscapulohumeral muscular dystrophy (FSHD) and provides perspectives to facilitate future research. RECENT FINDINGS: Clinically, imaging studies have contributed to a detailed characterization of the FSHD phenotype, and a model is proposed with five stages of disease progression. A number of clinical trials have been conducted regarding exercise and diet aiming to reduce symptoms. Genetically, at least two different mechanisms (FSHD1 and FSHD2) lead to double homeobox 4 (DUX4) expression in skeletal myocytes, which is expected to be necessary for the disease. Disease severity is most likely determined by a combination of the D4Z4 repeat size and its epigenetic state. SUMMARY: FSHD is one of the most common muscular dystrophies and is characterized by a typical distribution of muscle weakness. Progress has been made on clinical as well as on (epi)genetic aspects of the disease. Currently, there is no cure available for FSHD. For successful development of new treatments targeting the disease process, integration of clinical and pathogenetic knowledge is essential. A clinical trial toolbox that consists of patient registries, biomarkers and clinical outcome measures will be required to effectively conduct future clinical trials. PMID- 27389815 TI - The increasing relevance of nuclear envelope myopathies. AB - PURPOSE OF REVIEW: Nuclear envelope links to a wide range of disorders, including several myopathies and neuropathies over the past 2 decades, has spurred research leading to a completely changed view of this important cellular structure and its functions. However, the many functions now assigned to the nuclear envelope make it increasingly hard to determine which functions underlie these disorders. RECENT FINDINGS: New nuclear envelope functions in genome organization, regulation and repair, signaling, and nuclear and cellular mechanics have been added to its classical barrier function. Arguments can be made for any of these functions mediating abnormality in nuclear envelope disorders and data exist supporting many. Moreover, transient and/or distal nuclear envelope connections to other cellular proteins and structures may increase the complexity of these disorders. SUMMARY: Although the increased understanding of nuclear envelope functions has made it harder to distinguish specific causes of nuclear envelope disorders, this is because it has greatly expanded the spectrum of possible mechanisms underlying them. This change in perspective applies well beyond the known nuclear envelope disorders, potentially implicating the nuclear envelope in a much wider range of myopathies and neuropathies. PMID- 27389816 TI - New aspects of myofibrillar myopathies. AB - PURPOSE OF REVIEW: Myofibrillar myopathies (MFMs) are hereditary muscle disorders characterized by distinct histopathological features. This review provides an overview of recent research with respect to new disease genes, clinical phenotypes, insights into pathomechanisms and therapeutic strategies. RECENT FINDINGS: Beyond the known disease genes DES, FLNC, MYOT, CRYAB, ZASP, BAG3, FHL1 and TTN, mutations in PLEC, ACTA1, HSPB8 and DNAJB6 have also been associated with a MFM phenotype. Proteomic analysis revealed new information about the composition of protein aggregates in myotilinopathy and identified a new diagnostic marker. New animal models mirror central aspects of MFM pathology and novel therapeutic strategies for treatment of MFM were evaluated in cell and animal models. SUMMARY: MFMs are an expanding and numerically significant group of protein aggregate diseases with marked clinical and genetic heterogeneity. Though no specific therapy is currently available, the generation of patient mimicking cell and animal models now paves the way for the preclinical evaluation of novel therapeutic strategies. PMID- 27389817 TI - Highly Efficient Photocatalysts and Continuous-Flow Photocatalytic Reactors for Degradation of Organic Pollutants in Wastewater. AB - One of the most important applications for photocatalysis is engineered water treatment that photodegrades organic pollutants in wastewater at low cost. To overcome the low efficiency of batch degradation methods, continuous-flow photocatalytic reactors have been proposed and have become the most promising method for mass water treatment. However, most commercial semiconductor photocatalysts are granular nanoparticles with low activity and a narrow active light wavelength band; this creates difficulties for direct use in continuous flow photocatalytic reactors. Therefore, a high-performance photodegradation photocatalyst with proper morphology or structure is key for continuous photocatalytic degradation. Moreover, a well-designed photocatalytic device is another important component for continuous-flow photocatalysis and determines the efficiency of photocatalysis in practical water treatment. This review describes the basic design principles and synthesis of photocatalysts with excellent performance and special morphologies suitable for a filtering photocatalysis process. Certain promising continuous photodegradation reactors are also categorized and summarized. Additionally, selected scientific and technical problems that must be urgently solved are suggested. PMID- 27389818 TI - Health benefits of dancing activity among Korean middle-aged women. AB - The purpose of this study was to understand the health benefits of line dancing activity in Korean middle-aged women. This study explored how Korean middle-aged women perceive health benefits through lived experiences of line dancing in their leisure time. Three themes emerged related to health benefits: (1) psychological benefit, (2) physical benefit, and (3) social benefit. This finding suggested that serious leisure experience aids health enhancements in the lives of Korean middle-aged women. This study also discusses the research implication that continuous participation in leisure activity is necessary for health improvement in Korean middle-aged women. PMID- 27389819 TI - Neonatal units in Wales are understaffed and under-resourced, says report. PMID- 27389820 TI - Structural, optical, and transport properties of nanocrystalline bismuth telluride thin films treated with homogeneous electron beam irradiation and thermal annealing. AB - We investigated the effects of homogeneous electron beam (EB) irradiation and thermal annealing treatments on the structural, optical, and transport properties of bismuth telluride thin films. Bismuth telluride thin films were prepared by an RF magnetron sputtering method at room temperature. After deposition, the films were treated with homogeneous EB irradiation, thermal annealing, or a combination of both the treatments (two-step treatment). We employed Williamson-Hall analysis for separating the strain contribution from the crystallite domain contribution in the x-ray diffraction data of the films. We found that strain was induced in the thin films by EB irradiation and was relieved by thermal annealing. The crystal orientation along c-axis was significantly enhanced by the two-step treatment. Scanning electron microscopy indicated the melting and aggregation of nano-sized grains on the film surface by the two-step treatment. Optical analysis indicated that the interband transition of all the thin films was possibly of the indirect type, and that thermal annealing and two-step treatment methods increased the band gap of the films due to relaxation of the strain. Thermoelectric performance was significantly improved by the two-step treatment. The power factor reached a value of 17.2 MUW (cm(-1) K(-2)), approximately 10 times higher than that of the as-deposited thin films. We conclude that improving the crystal orientation and relaxing the strain resulted in enhanced thermoelectric performance. PMID- 27389821 TI - Treatment efficacy of Ampicillin/Sulbactam in comparison to alternative beta lactams for severe Acinetobacter baumannii infections. PMID- 27389822 TI - Invasive Esophageal Candidiasis with Chronic Mediastinal Abscess and Fatal Pneumomediastinum. AB - BACKGROUND Invasive candidiasis is a potential problem for patients receiving long-term immunosuppressive treatment. Psoriatic arthritis is one of many chronic diseases that can be successfully treated with immunosuppressive drugs, in spite of a documented and accepted risk for infectious complications. Critical awareness of possible infection must be part of the surveillance of such patients. CASE REPORT This is the case of a 68-year-old Norwegian male, treated with long-term immunosuppression for psoriatic arthritis, hospitalized with acute subcutaneous and mediastinal emphysema of unknown cause. He died of acute respiratory failure with circulatory collapse shortly after admission. The autopsy revealed mediastinal and subcutaneous emphysema and a mediastinal abscess containing Candida with probable entrance from the esophagus. CONCLUSIONS We consider invasive candidiasis of the esophagus to be the cause of both the chronic abscess and the acute mediastinal emphysema. This case illustrates the importance of awareness of invasive candidiasis as a possible complication in a patient with long-term immunosuppression. PMID- 27389823 TI - Tissue valves are preferable for patients with end-stage renal disease: an aggregate meta-analysis. AB - BACKGROUND: Valve selection in patients with end-stage renal disease (ESRD) is uncertain. We performed a systematic review and meta-analysis to compare clinical outcome in ESRD patients undergoing valve replacement. METHODS: We systematically searched multiple databases (2000-October 2015) to identify original studies comparing adverse events between mechanical and biological valve replacement in ESRD patients. End-points studied were: postoperative mortality, bleeding events, need for re-operation, and late survival. A random-effect inverse-variance weighted analysis was performed; event rates are compared as odds ratio (OR and 95% confidence interval) and hazard ratios (HR) for time-to-event data. Mechanical valve and tissue valve replacement were considered as study and control cohorts, respectively. RESULTS: Fifteen retrospective studies (5523 mechanical and 1600 tissue valve) were included in our meta-analysis. Early mortality was comparable (OR 1.15 [0.77; 1.72]; p = 0.49). The mean follow-up among studies ranged from 1.6-15 years. Bleeding was significantly higher after mechanical valve replacement (OR 2.55 [1.53; 4.26]; p = 0.0003). Structural valve degeneration was present in only 0.6% patients after a tissue valve replacement. Overall survival after valve replacement was poor (median 2.61 years); valve choice did not influence this outcome (pooled HR 0.87 [0.73; 1.04]; p = 0.14). CONCLUSION: Operative mortality in ESRD patients is comparable between mechanical and tissue valve replacement. Major bleeding episodes are significantly higher after mechanical valve replacement but structural degeneration in tissue valves during the follow-up period is low. Based on the findings from this meta analysis, we would recommend using tissue valves in patients with ESRD. PMID- 27389824 TI - Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats. AB - Insulin resistance is known to be a risk factor for cognitive impairment, most likely linked to insulin signaling, microglia overactivation, and beta amyloid (Abeta) deposition in the brain. Exenatide, a long lasting glucagon-like peptide 1 (GLP-1) analogue, enhances insulin signaling and shows neuroprotective properties. Pioglitazone, a peroxisome proliferated-activated receptor-gamma (PPAR-gamma) agonist, was previously reported to enhance cognition through its effect on Abeta accumulation and clearance. In the present study, insulin resistance was induced in male rats by drinking fructose for 12 weeks. The effect of monotherapy with pioglitazone (10 mg.kg(-1)) and exenatide or their combination on memory dysfunction was determined and some of the probable underlying mechanisms were studied. The current results confirmed that (1) feeding male rats with fructose syrup for 12 weeks resulted in a decline of learning and memory registered in eight-arm radial maze test; (2) treatment with pioglitazone or exenatide enhanced cognition, reduced hippocampal neurodegeneration, and reduced hippocampal microglia expression and beta amyloid oligomer deposition in a manner that is equal to monotherapies. These results may give promise for the use of pioglitazone or exenatide for ameliorating the learning and memory deficits associated with insulin resistance in clinical setting. PMID- 27389826 TI - REPLY. PMID- 27389825 TI - Independent and core pathways in oncogenic KRAS signaling. PMID- 27389827 TI - PdII and PtII complexes with a thio-aza macrocycle ligand containing an intercalating fragment: Structural and antitumor activity studies. AB - Two new PtII and PdII complexes of formula [LMCl2] (M=Pt, Pd) were synthesized and characterized both in solution and solid state. They were obtained using the thio-aza macrocycle 9,18-dimethyl-12,17dithia-9,18,27,28-tetraaaza-29 oxatetracyclo[24.2.1.02,7.020,25]enneicosa-2,4,6,20,22,24,26,281-octaene (L) containing the 2,5-diphenyl [1, 3, 4]oxadiazole as intercalating fragment. MII is coordinated in cis-position by the two S atoms of L. The two crystal structures of [LPtCl2] and [LPdCl2] complexes showed that the MII ion is located outside the macrocyclic cavity. The square planar coordination sphere is fulfilled by two chloride anions in a cisplatin-like arrangement with the chloride leaving groups exposed to the environment. The biological activity of both [LPtCl2] and [LPdCl2], monitored towards a leukemic cellular model (U937), is coherent with their ability to interfere, at different levels, with the DNA structure. PMID- 27389828 TI - Investigating the cytotoxicity of platinum(II) complexes incorporating bidentate pyridyl-1,2,3-triazole "click" ligands. AB - Six platinum(II) complexes of the type [Pt(PL)(AL)]2+, where PL is a bidentate pyridyl-1,2,3-triazole "click" ligand and AL is the R,R or S,S isomer of 1.2 diaminocyclohexane, have been synthesised and characterised by several methods including elemental microanalysis, proton NMR spectroscopy and X-ray crystallography. The in vitro cytotoxicity of each complex was assessed in eleven cell lines, revealing moderate to good activity for complexes incorporating 2-(1 phenyl-1H-1,2,3-triazol-4-yl)pyridine. PMID- 27389829 TI - The impact of hospital and urban wastewaters on the bacteriological contamination of the water resources in Kinshasa, Democratic Republic of Congo. AB - Although the United Nations General Assembly recognized in 2010 the right to safe and clean drinking water and sanitation as a human right that is essential to the full enjoyment of life and all other human rights, the contamination of water supplies with faecal pathogens is still a major and unsolved problem in many parts of the world. In this study, faecal indicator bacteria (FIB), including Escherichia coli (E. coli) and Enterococcus (ENT), were quantified over the period of June/July 2014 and June/July 2015 to assess the quality of hospital effluents (n = 3: H1, H2 and H3) and of rivers receiving wastewaters from the city of Kinshasa, Democratic Republic of Congo. The water and sediment samples from the river-receiving systems were collected in, upstream and downstream of the hospital outlet pipe (HOP) discharge. The analysis of E. coli and ENT in water and sediment suspension was performed using the cultural membrane filter method. The FIB characterization was performed for general E. coli, Enterococcus faecalis(E. faecalis) and human-specific Bacteroides by PCR using specific primers. The results revealed very high FIB concentration in the hospital effluent waters, with E. coli reaching the values of 4.2 * 10(5), 16.1 * 10(5) and 5.9 * 10(5) CFU 100 mL(-1), for the hospital effluents from H1, H2, and H3, respectively; and Enterococcus reaching the values of 2.3 * 10(4), 10.9 * 10(4) and 4.1 * 10(4) CFU 100 mL(-1), respectively. Interestingly, the FIB levels in the water and sediment samples from river-receiving systems are spatially and temporally highly variable and present in some samples with higher values than the hospital effluents. The PCR assays for human-specific Bacteroides HF183/HF134 further indicate that more than 98% of bacteria were from human origin. The results of this research therefore confirm the hypothesis of our previous studies, indicating that in developing countries (e.g., Democratic Republic of Congo and South India), the hospital effluent waters can be a significant source of the deterioration of the bacteriological quality for urban rivers. The approach used in this investigation can be further used to decipher the pollution of water resources by human faecal contamination. The results of this research will help to better understand the microbiological pollution problems in river receiving systems and will guide municipality decisions on improving the urban water quality. PMID- 27389830 TI - Theoretical predication of temperature effect on conducting processes in simulated amyotrophic lateral sclerosis at 20-40[Formula: see text]C. AB - The present study investigates action potential abnormalities in previously simulated cases of amyotrophic lateral sclerosis, termed as ALS1, ALS2 and ALS3, respectively, when the temperature is changed from 20[Formula: see text]C to 42[Formula: see text]C. These ALS cases are modeled as three progressively severe axonal abnormalities. The effects of temperature on the kinetics of currents, defining action potentials in the normal and abnormal cases, are also given and discussed. These computations use our temperature-dependent multi-layered model of human motor nerve fibers. The results show that the classical "transient" sodium current ([Formula: see text]) contributes mainly to the nodal action potential generation in the normal and abnormal cases for the temperature range of 20-39[Formula: see text]C, as the contribution of fast and slow potassium currents ([Formula: see text] and [Formula: see text]) to the total ionic current ([Formula: see text]) is negligible. However, the contribution of [Formula: see text] and [Formula: see text] to the membrane repolarization is enhanced at temperatures higher than 39[Formula: see text]C, especially at 42[Formula: see text]C, and the after-potentials are hyperpolarized in the normal and ALS1 cases, while, they are re-depolarized in the ALS2 and ALS3 cases. The ionic channels beneath the myelin sheath are insensitive to the short-lasting current stimuli and do not contribute to the internodal action potential generation for the normal and abnormal cases in the whole investigated temperature range. Nevertheless that the uniform axonal dysfunction progressively increases in the nodal and internodal segments of each next simulated ALS case, the action potentials cannot be regarded as definitive indicators for the progressive degrees of this disease, when the temperature is changed from 20[Formula: see text]C to 42[Formula: see text]C. However, the results are essential for the interpretation of mechanisms of action potential measurements in ALS patients with symptoms of cooling, warming and fever, which can result from alteration in body temperature. Our results also suggest that the conducting processes in patients with ALS are in higher risk during hyperthermia ([Formula: see text]C) than hypothermia ([Formula: see text]C). PMID- 27389832 TI - Reasons Why a Paper Is Not Selected for Publication in the Acta Chirurgica Belgica. PMID- 27389831 TI - Longitudinal live imaging of retinal alpha-synuclein::GFP deposits in a transgenic mouse model of Parkinson's Disease/Dementia with Lewy Bodies. AB - Abnormal alpha-synuclein (alpha-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated alpha-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused alpha-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged alpha-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the alpha-syn::GFP positive cells were retinal ganglion cells containing alpha-syn. Accumulation of alpha-syn persisted in the same cells and increased with age. Accumulation of alpha-syn::GFP was reduced by immunization with single chain antibodies against alpha-syn. In conclusion, longitudinal live imaging of the retina in the PDGF alpha-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of alpha-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting alpha-syn. PMID- 27389833 TI - Sleep arrangements, parent-infant sleep during the first year, and family functioning. AB - The present longitudinal study addressed the ongoing debate regarding the benefits and risks of infant-parent cosleeping by examining associations between sleep arrangement patterns across the first year of life and infant and parent sleep, marital and family functioning, and quality of mothers' behavior with infants at bedtime. Patterns of infant sleep arrangements across the infants' first year were derived from information obtained from 139 families at 1, 3, 6, 9, and 12 months of infant age in a central Pennsylvania sample. Linkages between these patterns and parent-infant sleep, marital and coparenting stress, and maternal behavior at bedtime (from video-recordings) were assessed. Compared with families whose infants were solitary sleepers by 6 months, persistent cosleeping was associated with sleep disruption in mothers but not in infants, although mothers in persistent cosleeping arrangements reported that their infants had more frequent night awakenings. Persistent cosleeping was also associated with mother reports of marital and coparenting distress, and lower maternal emotional availability with infants at bedtime (from home observations). Persistent cosleeping appeared to be a marker of, though not necessarily a cause of, heightened family stress, although the present design did not enable strong tests of causal processes, and results may be particular to cultures that are not supportive of cosleeping. Findings are discussed in terms of cultural contexts of infant sleep and the need for further investigations into the role of the health of the family system in influencing how parents structure infant sleep. (PsycINFO Database Record PMID- 27389834 TI - Mothers' depressive symptoms and children's cognitive and social agency: Predicting first-grade cognitive functioning. AB - Using data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (N = 1,364), the present study supports an agentic perspective; it demonstrates that mothers' depressive symptoms in infancy predict children's poor first-grade cognitive functioning because depressive symptoms predict children's low social and cognitive agency low motivation to initiate social interaction and actively engage in activities. When mothers' depressive symptoms were high in infancy, children displayed poor first-grade cognitive functioning due to (a) tendencies to become socially withdrawn by 36 months and low in mastery motivation by 54 months and (b) tendencies for children's low agency to predict declines in mothers' sensitivity and cognitive stimulation. Findings suggest that mothers' depressive symptoms undermine cognitive development through bidirectional processes centered on children's low motivation to engage in social interaction and initiate and persist at everyday tasks. (PsycINFO Database Record PMID- 27389835 TI - Significant elevation of carcinoembryonic antigen levels in abdominal drains after colorectal surgery may indicate early anastomotic dehiscence. AB - BACKGROUND: Anastomotic leak after colorectal surgery is a severe complication leading to major postoperative morbidity and mortality. Leaks typically present on the 5th to 6th postoperative days; however, early anastomotic dehiscence occurs occasionally. This study evaluated carcinoembryonic antigen (CEA) levels in abdominal drains after colorectal resection to assess its potential as an early marker to predict anastomotic leaks. METHODS: This prospective study included 105 patients undergoing elective colorectal surgery. Fluids from the patients' abdominal drain system were sampled daily for up to 3 days after surgery and evaluated for CEA levels. RESULTS: Early anastomotic dehiscence occurred in 3 patients (2.8%) and was associated with a significant elevation of CEA in drain fluids (above 1,000 ng/mL). However, in patients who developed late leaks (7 patients, 6.7%) no significant elevation of CEA was observed. CONCLUSIONS: Significant elevation of CEA levels in abdominal drains in the early postoperative period may indicate early anastomotic dehiscence. PMID- 27389836 TI - Persistent Blurry Vision After a Routine Eye Examination. PMID- 27389837 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 173-177, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 173-177, 2000. PMID- 27389838 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 210-213, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 210-213, 2000. PMID- 27389839 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 178-180, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 178-180, 2000. PMID- 27389840 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 181-183, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 181-183, 2000. PMID- 27389841 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 184-186, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 184-186, 2000. PMID- 27389842 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 187-189, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 187-189, 2000. PMID- 27389843 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 190-193, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 190-193, 2000. PMID- 27389844 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 198-201, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 198-201, 2000. PMID- 27389845 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 202-205, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 202-205, 2000. PMID- 27389846 TI - Errata. AB - We regret to report the following errors on Vol. 64, No. 1 which were caused by our printer. Please correct the page numbers (pp. 173-190 and pp. 198-210) on the running head with the stickers provided. Wrong:Biosci. Biotechnol. Biochem., 63 (7), 206-209, 1999 Right:Biosci. Biotechnol. Biochem., 64 (1), 206-209, 2000. PMID- 27389847 TI - Symptom Recognition and Perceived Urgency of Help-Seeking for Rheumatoid Arthritis and Other Diseases in the General Public: A Mixed Method Approach. AB - OBJECTIVE: Clinical outcomes in rheumatoid arthritis (RA) are improved if the disease is treated early. However, treatment is often significantly delayed as a result of delayed help-seeking by patients who fail to recognize its symptoms or the need for rapid medical attention. Two studies were conducted to investigate the role of symptom recognition in help-seeking for the symptoms of RA, and compared this to symptom recognition and help-seeking in angina and bowel cancer. METHODS: A qualitative interview study with 31 individuals and a survey of 1,088 members of the general public (all without RA) were conducted. Both studies used vignettes describing the symptoms of RA, bowel cancer, and angina. Participants made causal attributions and rated the perceived seriousness of the symptoms and the urgency with which they would seek medical help if confronted with these symptoms. RESULTS: Only a small proportion of participants in both studies recognized the symptoms of RA, whereas the symptoms of bowel cancer and angina were readily recognized by many participants and considered to be more serious and to require more rapid medical attention (Z = 14.7-34.2, P < 0.001). CONCLUSION: Accurate symptom attribution and the perception that symptoms are indicative of a serious underlying condition are both important drivers for rapid help-seeking. In the case of angina and bowel cancer, recent campaigns have promoted not only recognition of symptoms and their seriousness, but also emphasized the consequences of not seeking timely help. Our results suggest that these consequences should also be addressed in any public health campaign for RA. PMID- 27389848 TI - The Antibacterial Applications of Graphene and Its Derivatives. AB - Graphene materials have unique structures and outstanding thermal, optical, mechanical and electronic properties. In the last decade, these materials have attracted substantial interest in the field of nanomaterials, with applications ranging from biosensors to biomedicine. Among these applications, great advances have been made in the field of antibacterial agents. Here, recent advancements in the use of graphene and its derivatives as antibacterial agents are reviewed. Graphene is used in three forms: the pristine form; mixed with other antibacterial agents, such as Ag and chitosan; or with a base material, such as poly (N-vinylcarbazole) (PVK) and poly (lactic acid) (PLA). The main mechanisms proposed to explain the antibacterial behaviors of graphene and its derivatives are the membrane stress hypothesis, the oxidative stress hypothesis, the entrapment hypothesis, the electron transfer hypothesis and the photothermal hypothesis. This review describes contributions to improving these promising materials for antibacterial applications. PMID- 27389849 TI - Taking health geography out of the academy: Measuring academic impact. AB - In recent years the academic landscape has been shifting and significantly affected by the introduction of an 'impact agenda'. Academics are increasingly expected to demonstrate their broader engagement with the world and evidence related outcomes. Whilst different countries are at various stages along this impact journey, the UK is the first country to link impact to funding outcomes; here impact now accounts for 20% of an academic unit of assessment's Research Excellence Framework (REF) result. This concept of 'research impact' implies that our work can effect change through one or more identifiable events in a direct, preferably linear and certainly measurable manner. In this paper, focusing on impact in social science, and policy-related impact in particular, we argue that such a cause and effect model is inappropriate. Furthermore that impact is not immediate or indeed linear within social science research. Drawing on recent work on alcohol and tobacco environments in Scotland we present a case study of impact, reflect on the process and respond to the challenges of moving beyond 'business as usual' public participation towards the measurement of outcomes. In doing so we critique the way in which 'impact' is currently measured and suggest a move towards an enlightenment model with greater recognition of process. PMID- 27389850 TI - Identification of spatial and cohort clustering of tuberculosis using surveillance data from British Columbia, Canada, 1990-2013. AB - Since 2000, the global incidence of tuberculosis (TB) has decreased by 1.5% per year, becoming increasingly clustered in key subpopulations in low incidence settings. TB clustering can manifest spatially from recent transmission, or in non-spatial cohort clusters resulting from reactivation of latent infection in populations with shared risk factors. Identifying and interrupting disease clusters is required to eliminate TB in low incidence countries. Here we demonstrate an analytical approach for detecting both spatial and cohort clustering of TB among population subgroups, and describe the value in differentiating these forms of clustering. TB cases in British Columbia meeting the Canadian case definition were geocoded and mapped using Geographic Information Systems (GIS). Incidence rates were calculated for three periods (1990-1997, n = 2556; 1998-2005, n = 2488; 2006-2013, n = 2225) among Canadian born (CB) and foreign-born (FB) populations using denominator data from the Canadian Census. Spatial clusters were identified using a scanning window statistic (SaTScan) and overlaid on provincial incidence maps. Country of birth (cohort) clustering in the FB was identified using Lorenz curves and Gini coefficients. TB incidence in the CB population was generally low, but punctuated with few areas of high incidence; the spatial clusters identified in the CB match previously identified clusters. TB incidence in the FB did not show spatially localized clusters. However, Lorenz curves revealed substantial, and increasing, cohort clustering in the FB in semi-urban and rural regions of British Columbia, and less pronounced, and decreasing, clustering in urban regions. In general, the TB incidence in groups defined by country of birth shifted over time to become increasingly uniform across regions. Our approach, based on spatial analysis and the application of Lorenz curves revealed a complex coexistence of spatial and cohort clustering. Spatial and cohort clusters require differing public health responses, and differentiating types of clustering can inform TB prevention programs. PMID- 27389851 TI - Physiological and proteomic analysis reveals the different responses of Cunninghamia lanceolata seedlings to nitrogen and phosphorus additions. AB - Both nitrogen (N) and phosphorus (P) additions in soils can increase tree photosynthetic rate (Pn), biomass accumulation and further increase primary production of plantation. However, the improved photosynthetic ability is varied from the added nutrient types and the mechanisms are sophisticated. In this study, an iTRAQ-based quantitative proteome combined with physiological analysis of Chinese fir (Cunninghamia lanceolata) leaves was performed to determine the common and different responses on photosynthetic process to the N and P additions. The results showed that, either N or P added in soils significantly increased Pn, but N addition had more positive effects than P addition in improving photosynthetic ability. Physiologically, N addition caused more in improving photosynthetic rate than P addition, which attributes to higher leaf N and chlorophyll contents, enlarged chloroplast size and more number of thylakoids. Proteomic data revealed that the increased Pn to N and P additions may attribute to the increased abundance of proteins involved in carbon fixation and RuBP regeneration during the light-independent reactions. However, N addition increased the abundance of photosystem II related proteins and P addition increased the abundance of photosystem I related proteins. Additionally, proteomic data also gave some clues on the different metabolic processes caused by N and P additions on glycolysis and TCA cycle, which were potentially related to higher growth and developmental rates of C. lanceolata. Therefore, this study provides new insights into the different photosynthesis and metabolic processes of Chinese fir in response to N and P additions. BIOLOGICAL SIGNIFICANCE: Fertilization is an important management measure to improve timber yield and primary production of Cunninghamia lanceolata, which is the largest planted coniferous species in southeast China. Nitrogen (N) and phosphorus (P) additions into soils can improve tree photosynthesis, and further increase plantation production. However, the mechanism of N and P additions in improving photosynthesis is still unclearly. In this study, a physiological measurement combined with proteomic analysis was performed on a controlled experiment in the greenhouse. These results improve understanding of the essentially photosynthetic activity and metabolic process of C. lanceolata responding to N and P fertilization. PMID- 27389852 TI - Proteomic analysis of the venom and venom sac of the woodwasp, Sirex noctilio - Towards understanding its biological impact. AB - The European horntail woodwasp, Sirex noctilio, is an invasive insect that attacks conifer hosts, particularly Pinus species. Venom injected by female S. noctilio, together with its symbiotic fungus, damages the normal physiology of Pinus, leading to death of the tree. To identify the proteinaceous components in the venom and uncover the interplay between venom proteins and tree proteins, clarification of the overall profile of proteins produced in the venom gland apparatus was carried out in this work. The venom sac proteome utilised in solution digested in either a natural or deglycosylated state, prior to nanoHPLC LTQ-Orbitrap under CID/ETD mode. Here, we report the identification of 1454 and 1225 proteins in venom and sac, respectively, with 410 mutual proteins. Approximately 90 proteins were predicted to be secretory, of which 8 have features characteristic of toxins. Chemosensory binding proteins were also identified. Gene ontology and KEGG pathway analysis were employed to predict the protein functions and biological pathways in venom and sac. Protein-protein interaction (PPI) analysis suggested that one-step responses represent the majority of the Sirex-Pinus PPIs, and the proteins representing network hub nodes could be of importance for the development of pest management strategies. SIGNIFICANCE: The woodwasp Sirex noctilio is an invasive species in many parts of the world, including Australia and North America, where it is considered within the top 10 most serious forest insects. Where they have been introduced, the female woodwasps attack living pine trees, causing significant economic losses. Central to this destruction is the woodwasp's life cycle requirement to bore a hole to deposit eggs and a toxic mucus that disables the tree's network for transporting water and nutrients, yet aids in larval survival. Here we specifically examine the mucus gland apparatus and its contents, revealing the protein components that together with 'noctilisin' facilitate this complex association. The identification of chemosensory binding proteins further supports a role for the woodwasp ovipositor as an instrument for early stages of host tree selection. These findings could provide important clues towards the development of novel control tools against this pest. PMID- 27389853 TI - Review on proteomics for food authentication. AB - Consumers have the right to know what is in the food they are eating. Accordingly, European and global food regulations require that the provenance of the food can be guaranteed from farm to fork. Many different instrumental techniques have been proposed for food authentication. Although traditional methods are still being used, new approaches such as genomics, proteomics, and metabolomics are helping to complement existing methodologies for verifying the claims made about certain food products. During the last decade, proteomics (the large-scale analysis of proteins in a particular biological system at a particular time) has been applied to different research areas within food technology. Since proteins can be used as markers for many properties of a food, even indicating processes to which the food has been subjected, they can provide further evidence of the foods labeling claim. This review is a comprehensive and updated overview of the applications, drawbacks, advantages, and challenges of proteomics for food authentication in the assessment of the foods compliance with labeling regulations and policies. SIGNIFICANCE: This review paper provides a comprehensive and critical overview of the application of proteomics approaches to determine the authenticity of several food products updating the performances and current limitations of the applied techniques in both laboratory and industrial environments. PMID- 27389854 TI - QSAR Studies and Design of Some Tetracyclic 1,4-Benzothiazines as Antimicrobial Agents. AB - A quantitative structure-activity relationship (QSAR) analysis has been performed on a series of 20 tetracyclic 1,4-benzothiazines (1a-1t) with antimicrobial activity to explain the observed biological activity trend on structural basis. Multiple linear regression (MLR) method was employed to establish statistically significant QSAR models. The developed models are robust, predictive and free from chance correlation with good fitting ability and sufficient generalizability. These studies revealed the dominance of WHIM parameters in describing antimicrobial activity of the title compounds. Further, design of some more active compounds is presented. PMID- 27389855 TI - Intriguing Morphology Evolution from Noncrosslinked Poly(tert-butyl acrylate) Seeds with Polar Functional Groups in Soap-Free Emulsion Polymerization of Styrene. AB - Herein, we demonstrate a facile approach to prepare anisotropic poly(tert-butyl acrylate)/polystyrene (PtBA/PS) composite particles with controllable morphologies by soap-free seeded emulsion polymerization (SSEP). In the first step, noncrosslinked PtBA seeds with self-stabilizing polar functional groups (e.g., ester groups and radicals) are synthesized by soap-free emulsion polymerization. During the subsequent SSEP of styrene (St), PS bulges are nucleated on the PtBA seeds due to the microphase separation confined in the latex particles. The morphology evolution of PtBA/PS composite particles is tailored by varying the monomer/seed feed ratio, polymerization time, and polymerization temperature. Many intriguing morphologies, including hamburger like, litchi-like, mushroom-like, strawberry-like, bowl-like, and snowman-like, have been acquired for PtBA/PS composite particles. The polar groups on the PtBA seed surface greatly influence the formation and further merging of PS/St bulges during the polymerization. A possible formation mechanism is proposed on the basis of experimental results. These complex composite particles are promising for applications in superhydrophobic coatings. PMID- 27389856 TI - Microbial protein: future sustainable food supply route with low environmental footprint. AB - Microbial biotechnology has a long history of producing feeds and foods. The key feature of today's market economy is that protein production by conventional agriculture based food supply chains is becoming a major issue in terms of global environmental pollution such as diffuse nutrient and greenhouse gas emissions, land use and water footprint. Time has come to re-assess the current potentials of producing protein-rich feed or food additives in the form of algae, yeasts, fungi and plain bacterial cellular biomass, producible with a lower environmental footprint compared with other plant or animal-based alternatives. A major driver is the need to no longer disintegrate but rather upgrade a variety of low-value organic and inorganic side streams in our current non-cyclic economy. In this context, microbial bioconversions of such valuable matters to nutritive microbial cells and cell components are a powerful asset. The worldwide market of animal protein is of the order of several hundred million tons per year, that of plant protein several billion tons of protein per year; hence, the expansion of the production of microbial protein does not pose disruptive challenges towards the process of the latter. Besides protein as nutritive compounds, also other cellular components such as lipids (single cell oil), polyhydroxybuthyrate, exopolymeric saccharides, carotenoids, ectorines, (pro)vitamins and essential amino acids can be of value for the growing domain of novel nutrition. In order for microbial protein as feed or food to become a major and sustainable alternative, addressing the challenges of creating awareness and achieving public and broader regulatory acceptance are real and need to be addressed with care and expedience. PMID- 27389857 TI - How stem cells manage to escape senescence and ageing - while they can: A recent study reveals that autophagy is responsible for senescence-dependent loss of regenerative potential of muscle stem cells during ageing. AB - Skeletal muscle stem cells or satellite cells are responsible for muscle regeneration in the adult. Although satellite cells are highly resistant to stress, and display greater capacity to repair molecular damage than the committed progeny, their regenerative potential declines with age. During ageing, satellite cells switch to a state of permanent cell cycle arrest or senescence which prevents their activation. A recent study reveals that the senescence of satellite cell relies on defective autophagy, the quality control mechanism that degrades damaged proteins and organelles. Molecular damage is generated by oxidative stress that also promotes epigenetic changes that activate the expression of master genes, in a double-hit mechanism that ensures senescence. Importantly, genetic, and pharmacological correction of defective autophagy reverses satellite cell senescence and restores muscle regeneration in geriatric mice, with perspectives of modulating age-related functional decline of muscle. This study provides new clues to understand stem cell and organismal ageing. PMID- 27389858 TI - Ultraweak Photon Emission from the Seed Coat in Response to Temperature and Humidity-A Potential Mechanism for Environmental Signal Transduction in the Soil Seed Bank. AB - Seeds beneath the soil sense the changing environment to time germination and seedling emergence with the optimum time of year for survival. Environmental signals first impact with the seed at the seed coat. To investigate whether seed coats have a role in environmental sensing we investigated their ultraweak photon emission (UPE) under the variable temperature, relative humidity and oxygen conditions they could experience in the soil seed bank. Using a custom-built luminometer we measured UPE intensity and spectra (300-700 nm) from Phaseolus vulgaris seeds, seed coats and cotyledons. UPE was greatest from the internal surface of the seed coat. Seed coat UPE increased concomitantly with both increasing temperature and decreasing relative humidity. Emission was oxygen dependent and it was abolished by treatment with dinitrophenylhydrazine, demonstrating the key role of seed coat carbonyls in the phenomenon. We hypothesize that beneath the soil surface the attenuation of light (virtual darkness: low background noise) enables seeds to exploit UPE for transducing key environmental variables in the soil (temperature, humidity and oxygen) to inform them of seasonal and local temperature patterns. Overall, seed coats were found to have potential as effective transducers of key fluctuating environmental variables in the soil. PMID- 27389859 TI - Synergism and effect of high initial volatile fatty acid concentrations during food waste and pig manure anaerobic co-digestion. AB - Anaerobic co-digestion of food waste (FW) and pig manure (PM) was undertaken in batch mode at 37 degrees C in order to identify and quantify the synergistic effects of co-digestion on the specific methane yield (SMY) and reaction kinetics. The effects of the high initial volatile fatty acid (VFA) concentrations in PM on synergy observed during co-digestion, and on kinetic modelling were investigated. PM to FW mixing ratios of 1/0, 4/1, 3/2, 2/3, 1/4 and 0/1 (VS basis) were examined. No VFA or ammonia inhibition was observed. The highest SMY of 521+/-29ml CH4/gVS was achieved at a PM/FW mixing ratio of 1/4. Synergy in terms of both reaction kinetics and SMY occurred at PM/FW mixing ratios of 3/2, 2/3 and 1/4. Initial VFA concentrations did not explain the synergy observed. Throughout the study the conversion of butyric acid was inhibited. Due to the high initial VFA content of PM, conventional first order and Gompertz models were inappropriate for determining reaction kinetics. A dual pooled first order model was found to provide the best fit for the data generated in this study. The optimal mixing ratio in terms of both reaction kinetics and SMY was found at a PM/FW mixing ratio of 1/4. PMID- 27389860 TI - Recycling ash into the first stage of cyclone pre-heater of cement kiln. AB - Fly ash collected from the bag filter could be recycled into the first stage of the cyclone pre-heater of the cement kiln, resulting in the possible enrichment of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). In this study, soxhlet fly ash (SFA) and raw meal (RM) were selected as the basis for the PCDD/F formation experiments. The levels of 2,3,7,8-PCDD/Fs formed on the SFA and RM were observed to be 2550pg/g (157pg I-TEQ/g) and 1142pg/g (55pg I-TEQ/g), respectively. While less 2,3,7,8-PCDD/Fs was detected when SFA was mixed with RM, suggesting that recycling cement kiln ash would not largely increase the concentration of PCDD/Fs in flue gas. Furthermore, the possible influencing factors on the PCDD/F formation were also investigated. The formation of 2,3,7,8 PCDD/Fs was up to 10,871pg/g (380pg I-TEQ/g) with the adding of CuCl2, which was much higher than the results of CuO and activated carbon. Most importantly, the homologue, congener and gas/particle distribution of PCDD/Fs indicated that de novo synthesis was the dominant PCDD/F formation pathway for SFA. Lastly, principal component analysis (PCA) was also conducted to identify the relationship between the compositions of reactant and the properties of PCDD/Fs produced. PMID- 27389861 TI - Withdrawal of posttransplant hepatitis B virus prophylaxis: A blind test. PMID- 27389863 TI - Reversible dissolution/formation of polymer nanoparticles controlled by visible light. AB - Noncovalent crosslinking between polyvinyl pyridine and a copolymer of acrylic acid led to the formation of a polymer nanoparticle. In the presence of a metastable-state photoacid, reversible dissolution and formation of the nanoparticle can be controlled by visible light. Photo-induced proton transfer from the photoacid to the polymers broke the hydrogen bonding and ionic bonding and led to the dissolution of the nanoparticle. Cycles of dissolution and formation were controlled by turning on and off irradiation, and were demonstrated by the transmittance change. PMID- 27389862 TI - Preliminary evaluation of a new kit for differentiation of Mycobacterium tuberculosis complex species using Speed-Oligo MTBC. AB - We present the first evaluation of a novel molecular assay, the Speed-Oligo Mycobacterium tuberculosis complex (SO-MTBC), which is based on PCR combined with a dipstick for the differentiation of M. tuberculosis complex (MTBC) members. The results of this assay were compared with findings obtained using the Genotype MTBC assay. In this study, 189 strains of MTBC isolates from 2011 to 2014 were evaluated to determine the MTBC species. Most (174, 92 %) of the strains were identified as M. tuberculosissensu stricto, 7 (3.7 %) as Mycobacteriumbovis, 5 (2.6 %) as M. bovis bacillus Calmette-Guerin, 2 (1.1 %) as Mycobacteriumafricanum and 1 (0.5 %) as Mycobacteriumcaprae; no strains belonged to Mycobacteriummicroti and Mycobacteriumcanettii subsp. The concordance kappa coefficient obtained was 0.96 with the results of the Genotype MTBC assay. SO-MTBC may represent a fast and easy-to-use alternative for differentiating among MTBC subspecies in laboratories with standard equipment. PMID- 27389864 TI - Clinicopathologic evaluation of cytopenic patients with isolated trisomy 8: a detailed comparison between idiopathic cytopenia of unknown significance and low grade myelodysplastic syndrome. AB - The significance of an isolated trisomy 8 (+8) in the diagnosis of myelodysplastic syndrome (MDS) is not well established. It is common in MDS, but is not considered as an MDS-defining abnormality in the absence of morphologic dysplasia. We evaluated two groups of patients with isolated +8 and either low grade MDS (LG-MDS) or idiopathic cytopenia of undetermined significance (ICUS). At presentation, ICUS patients had a lower platelet count (85.0 vs 163.5 * 109 cells/L; p = 0.02), while MDS patients had more frequent incidence of isolated anemia (64% vs 0%, p = 0.007). A subset (36%) of ICUS patients progressed to MDS or AML. These patients presented with more severe neutropenia (0.9 vs 3.1 * 103/MUL, p = 0.01) and a trend toward a higher proportion (>50%) of +8 metaphases compared to those that did not progress (p = 0.05). Thus, ICUS patients with isolated +8 may progress to MDS and AML and deserve close clinical follow-up. PMID- 27389866 TI - Infrastructures for healthcare: From synergy to reverse synergy. AB - The Danish General Practitioners Database has over more than a decade developed into a large-scale successful information infrastructure supporting medical research in Denmark. Danish general practitioners produce the data, by coding all patient consultations according to a certain set of classifications, on the entire Danish population. However, in the Autumn of 2014, the system was temporarily shut down due to a lawsuit filed by two general practitioners. In this article, we ask why and identify a political struggle concerning authority, control, and autonomy related to a transformation of the fundamental ontology of the information infrastructure. We explore how the transformed ontology created cracks in the inertia of the information infrastructure damaging the long-term sustainability. We propose the concept of reverse synergy as the awareness of negative impacts occurring when uncritically adding new actors or purposes to a system without due consideration to the nature of the infrastructure. We argue that while long-term information infrastructures are dynamic by nature and constantly impacted by actors joining or leaving the project, each activity of adding new actors must take reverse synergy into account, if not to risk breaking down the fragile nature of otherwise successful information infrastructures supporting research on healthcare. PMID- 27389865 TI - Brief Report: CXCL10 Is a Possible Biomarker for the Development of Psoriatic Arthritis Among Patients With Psoriasis. AB - OBJECTIVE: Biomarkers that can predict the development of psoriatic arthritis (PsA) in patients with psoriasis would be useful in clinical practice. The aim of this study was to assess whether CXCL10 could be a predictive biomarker of PsA prior to its onset. METHODS: Psoriasis patients without arthritis were followed up prospectively and assessed annually for development of PsA by a rheumatologist. Patients in whom PsA developed were designated as converters, while those in whom PsA did not develop were termed nonconverters. Baseline serum concentrations of CXCL10 were measured by Luminex assay in 46 converters and 45 nonconverters. RESULTS: The level of CXCL10 was significantly higher in converters (median 493 pg/ml [interquartile range (IQR) 356-984]) than in nonconverters (median 371 pg/ml [IQR 263-578]; P = 0.005). In contrast, C reactive protein (CRP) levels were not significantly different between converters and nonconverters at baseline. CXCL10 was associated with conversion status after adjustment for age, sex, duration of psoriasis, and duration of follow-up (odds ratio 1.3, 95% confidence interval 1.1-1.5, P = 0.004). In a subset of converters, the CXCL10 level was significantly higher at baseline (median 927.4 pg/ml [IQR 547.6-1,243]) than after PsA diagnosis (491.5 pg/ml [IQR 323.2-607]; P < 0.0001), while CRP levels were lower at baseline (26.6 MUg/ml [IQR 16.37 62.75]) than after PsA diagnosis (36.1 MUg/ml [IQR 14.74-101.7]; P = 0.003). CXCL10 gene expression was increased 17.3-fold in synovial fluid (SF) compared with blood from PsA patients (P = 0.01) and 44.3-fold in the SF of PsA patients compared with the SF of patients with gout (P = 0.001). CONCLUSION: CXCL10 may be involved in PsA pathogenesis and is a candidate predictive biomarker for PsA in patients with psoriasis. PMID- 27389867 TI - Nanowire Magnetoscope Reveals a Cellular Torque with Left-Right Bias. AB - Cellular force regulates many types of cell mechanics and the associated physiological behaviors. Recent evidence suggested that cell motion with left right (LR) bias may be the origin of LR asymmetry in tissue architecture. As actomyosin activity was found essential in the process, it predicts a type of cellular force that coordinates the development of LR asymmetry in tissue formation. However, due to the lack of appropriate platform, cellular force with LR bias has not yet been found. Here we report a nanowire magnetoscope that reveals a rotating force-torque-exerted by cells. Ferromagnetic nanowires were deposited and internalized by micropatterned cells. Within a uniform, horizontal magnetic field, the nanowires that initially aligned with the magnetic field were subsequently rotated due to the cellular torque. We found that the torque is LR biased depending on cell types. While NIH 3T3 fibroblasts and human vascular endothelial cells exhibited counterclockwise torque, C2C12 myoblasts showed torque with slight clockwise bias. Moreover, an actin ring composed of transverse arcs and radial fibers was identified as a major factor determining the LR bias of cellular torque, since the disruption of actin ring by biochemical inhibitors or elongated cell shape abrogated the counterclockwise bias of NIH 3T3 fibroblasts. Our finding reveals a LR-biased torque of single cells and a fundamental origin of cytoskeletal chirality. More broadly, we anticipate that our method will provide a different perspective on mechanics-related cell physiology and force transmission necessary for LR propagation in tissue formation. PMID- 27389868 TI - Objective sinonasal functional outcomes in endoscopic anterior skull-base surgery: an evidence-based review with recommendations. AB - BACKGROUND: The use of endoscopic endonasal approaches to the anterior skull base has dramatically expanded in recent years, with clinical endpoints and complication rates that compare favorably to traditional approaches. The impact of the endoscopic approach on sinonasal function has been less rigorously evaluated. The purpose of this study was to systematically analyze the literature evaluating objective sinonasal outcomes in endoscopic anterior skull-base surgery, and provide evidence-based recommendations. METHODS: A systematic review of the literature was performed based on a published guideline for developing an evidence-based review with recommendations. Objective sinonasal outcomes included were olfaction, mucociliary clearance, and nasal airflow. RESULTS: Ten articles were identified addressing objective olfactory outcomes: 2 randomized controlled trials; 6 cohort studies; and 2 retrospective case series. One cohort study investigating mucociliary clearance was identified. Six studies reporting postoperative endoscopic outcomes were identified. CONCLUSION: Based on the available evidence, nasoseptal flap (NSF) elevation with or without use in reconstruction likely leads to impairment in objective olfactory function. Endoscopic sellar and parasellar surgery without the elevation of an NSF may lead to a transient reduction in olfactory function. In the absence of a high a priori risk of cerebrospinal fluid (CSF) leak, it is an option to avoid routine NSF elevation in sellar and parasellar procedures, with preservation of at least 1 vascular pedicle during the approach. Monopolar electrocautery for mucosal incisions may increase the risk of olfactory impairment. If an NSF is used, donor site defect reconstruction may be considered. PMID- 27389869 TI - Comparison of Antibiotic Resistance Removal Efficiencies Using Ozone Disinfection under Different pH and Suspended Solids and Humic Substance Concentrations. AB - This study mainly evaluated the effectiveness of ozonation toward the enhancement of the removal efficiencies of antibiotic-resistant bacteria (ARB), pB10 plasmid transfer, and pB10 plasmids under different pH and suspended solids (SS) and humic acid concentrations. First, chlorination was tested as a reference disinfection process. Chlorination at a very high dose concentration of Cl2 (75 mg L(-1)) and a long contact time (10 min) were required to achieve approximately 90% ARB and pB10 plasmid transfer removal efficiencies. However, even these stringent conditions only resulted in a 78.8% reduction of pB10 plasmid concentrations. In case of ozonation, the estimated CT (concentration * contact time) value (at C0 = 7 mg L(-1)) for achieving 4-log pB10 plasmid removal efficiency was 127.15 mg.min L(-1), which was 1.04- and 1.25-fold higher than those required for ARB (122.73 mg.min L(-1)) and a model nonantibiotic resistant bacterial strain, E. coli K-12, (101.4 mg.min L(-1)), respectively. In preventing pB10 plasmid transfer, ozonation achieved better performance under conditions of higher concentrations of humic acid and lower pH. Our study results demonstrated that the applicability of CT concept in practice, conventionally used for disinfection, might not be appropriate for antibiotic resistance control in the wastewater treatment process. Further studies should be conducted in wastewater engineering on how to implement multiple barriers including disinfection to prevent ARB and ARG discharge into the environment. PMID- 27389870 TI - Hong Kong domestic health spending: financial years 1989/90 to 2012/13. PMID- 27389871 TI - Optimum breeding strategies using genomic selection for hybrid breeding in wheat, maize, rye, barley, rice and triticale. AB - KEY MESSAGE: A breeding strategy with moderate nursery selection followed by genomic selection and one-stage phenotypic selection maximizes annual selection gain for grain yield across a wide range of hybrid breeding scenarios. Genomic selection (GS) is a promising method for the selection of quantitatively inherited traits but its most effective implementation in routine hybrid breeding schemes requires further research. We compared five breeding strategies and varied their available budget, the costs for doubled haploid (DH) line and hybrid seed production as well as variance components for grain yield in a wide range. In contrast to previous studies, we included a nursery selection for disease resistance just before GS on grain yield. The breeding strategy GSrapid with moderate nursery selection followed by one stage GS and one final stage with phenotypic selection on grain yield had the highest annual selection gain across all strategies, budgets, costs and variance components considered and we, therefore, highly recommend its use in hybrid breeding of cereals. Although selecting on traits not correlated with grain yield in the observation nursery, this selection reduced the selection gain of grain yield, especially in the breeding schemes with GS and for selected fractions smaller than 0.3. Owing to the very high number of test candidates entering breeding strategies with GS, the costs for DH line production had a larger impact on the annual selection gain than the hybrid seed production costs. The optimum allocation of test resources maximizing annual selection gain in classical two-stage phenotypic selection on grain yield and for the recommended breeding strategy GSrapid is finally explored for maize, wheat, rye, barley, rice and triticale. PMID- 27389872 TI - Exercise and Prostate Cancer: Evidence and Proposed Mechanisms for Disease Modification. AB - Exercise has many potential benefits in relation to cancer. Apart from primary prevention, these include improvement of nonspecific cancer-related symptoms, amelioration of symptoms and cardiovascular risk factors related to cancer treatment, and improvements in various quality-of-life-related factors. Increasing evidence also points toward improved cancer-free and overall survival in cancer patients who undertake regular exercise, findings which should encourage further research in this area. Obesity is known to be associated with a proinflammatory, prothrombotic humoral milieu, which may promote aggressiveness in prostate cancer through interactions with NK-cell-mediated killing of circulating tumor cells, through platelet-circulating tumor cell interactions, and through alterations in adipokine and myokine profile among others. Physical activity reduces levels of systemic inflammatory mediators and so exercise may represent an accessible and cost-effective means of ameliorating the proinflammatory effects of obesity in cancer patients. This review outlines the evidence for the benefits of exercise in these patients, focusing on prostate cancer, and delineates current theories of the underlying biological mechanisms. Cancer Epidemiol Biomarkers Prev; 25(9); 1281-8. (c)2016 AACR. PMID- 27389873 TI - Response: Letter to the Editor. PMID- 27389874 TI - Valley-engineered ultra-thin silicon for high-performance junctionless transistors. AB - Extremely thin silicon show good mechanical flexibility because of their 2-D like structure and enhanced performance by the quantum confinement effect. In this paper, we demonstrate a junctionless FET which reveals a room temperature quantum confinement effect (RTQCE) achieved by a valley-engineering of the silicon. The strain-induced band splitting and a quantum confinement effect induced from ultra thin-body silicon are the two main mechanisms for valley engineering. These were obtained from the extremely well-controlled silicon surface roughness and high tensile strain in silicon, thereupon demonstrating a device mobility increase of ~500% in a 2.5 nm thick silicon channel device. PMID- 27389875 TI - Tick holocyclotoxins trigger host paralysis by presynaptic inhibition. AB - Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis. PMID- 27389876 TI - Positive blood alcohol level in severe traumatic brain injury is associated with better long-term functional outcome. AB - OBJECTIVE: To investigate the association between positive blood alcohol level (BAL) and functional outcome in patients suffering severe traumatic brain injury. STUDY DESIGN: The brain trauma registry of an academic trauma centre was queried for patients admitted between January 2007 and December 2011. All patients (>= 18 years) with a neurosurgical intensive care length of stay beyond 2 days were included. Patient demographics, clinical characteristics, injury profile, laboratory test and outcomes were abstracted for analysis. Primary outcome was unfavourable functional outcome defined as Glasgow Outcome Score (GOS) <= 3. Multivariable regression models were used for analysis. RESULTS: Of the 352 patients, 39% were BAL (+) at admission. Patients with (+) BAL were significantly younger with less co-morbidities. The cohorts exhibited no significant difference in the severity of the intra-cranial injury and the use of intra-cranial monitoring or surgical interventions. Further, the groups presented no difference in in-hospital mortality (p = 0.1) or 1-year mortality (p = 0.5). There was a worse long-term functional outcome in (-) BAL patients compared to their BAL (+) counterparts after adjustment for confounders (GOS <= 3: AOR = 2.0, 95% CI = 1.1 3.5, p = 0.02). CONCLUSION: Positive BAL on admission is associated with a better long-term functional outcome in patients suffering severe traumatic brain injury. PMID- 27389877 TI - Receptor antagonism/agonism can be uncoupled from pharmacoperone activity. AB - Pharmacoperones rescue misrouted mutants of the vasopressin receptor type 2 (V2R) and enable them to traffic to the correct biological locus where they function. Previously, a library of nearly 645,000 structures was interrogated with a high throughput screen; pharmacoperones were identified for V2R mutants with a view toward correcting the underlying mutational defects in nephrogenic diabetes insipidus. In the present study, an orthologous assay was used to evaluate hits from the earlier study. We found no consistent relation between antagonism or agonism and pharmacoperone activity. Active pharmacoperones were identified which had minimal antagonistic activity. This increases the therapeutic reach of these drugs, since virtually all pharmacoperone drugs reported to date were selected from peptidomimetic antagonists. Such mixed-activity drugs have a complex pharmacology limiting their therapeutic utility and requiring their removal prior to stimulation of the receptor with agonist. PMID- 27389878 TI - Lentiviral vector-mediated down-regulation of Notch1 in endometrial stem cells results in proliferation and migration in endometriosis. AB - The recent characterization of stem/progenitor cells in the endometrium has shed new light for pathogenesis of endometriosis. The present study was undertaken to investigate the role of Notch1, known as a cell fate regulator, in the mechanism of endometriosis. Influence of Notch1 on endometrial stem cells proliferation and migration was evaluated by knocking down Notch1 expression using shRNA. Furthermore, human endometrial stromal and epithelial stem cells with or without LV-Notch1-shRNA were injected into the peritoneal cavity of nude mice, to assess the in vivo effects of a specific antagonist of Notch1 on the progression of endometriosis. The results showed that LV-Notch1-shRNA led to a significant decline of clonogenicity and migration in human endometrial stem cells in vitro, as well as the size of endometriotic lesions in murine models. These data provide evidence that specific inhibition of Notch1 alters endometriotic tissue growth and progression, and may represent a promising potential therapeutic avenue. PMID- 27389880 TI - Effects of computational phantoms on the effective dose and two-dosimeter algorithm for external photon beams. AB - In this study, the effect of computational phantoms on the effective dose (E), dosimeter responses positioned on the front (chest) and back of phantom, and two dosimeter algorithm was investigated for external photon beams. This study was performed using Korean Typical MAN-2 (KTMAN-2), Chinese Reference Adult Male (CRAM), ICRP male reference, and Male Adult meSH (MASH) reference phantoms. Calculations were performed for beam directions in different polar and azimuthal angles using the Monte Carlo code of MCNP at energies of 0.08, 0.3, and 1MeV. Results show that the body shape significantly affects E and two-dosimeter responses when the dosimeters are indirectly irradiated. The acquired two dosimeter algorithms are almost the same for all the mentioned phantoms except for KTMAN-2. Comparisons between the obtained E and estimated E (Eest), acquired from two-dosimeter algorithm, illustrate that the Eest is overestimated in overhead (OH) and underfoot (UF) directions. The effect of using one algorithm for all phantoms was also investigated. Results show that application of one algorithm to all reference phantoms is possible. PMID- 27389881 TI - Determination of neutron energy spectrum at KAMINI shielding experiment location. AB - The neutron spectrum at KAMINI reactor south beam tube end has been determined using multifoil activation method. This beam tube is being used for characterizing neutron attenuation of novel shield materials. Starting from a computed guess spectrum, the spectrum adjustment/unfolding procedure makes use of minimization of a modified constraint function representing (a) least squared deviations between the measured and calculated reaction rates, (b) a measure of sharp fluctuations in the adjusted spectrum and (c) the square of the deviation of adjusted spectrum from the guess spectrum. The adjusted/unfolded spectrum predicts the reaction rates accurately. The results of this new procedure are compared with those of widely used SAND-II code. PMID- 27389879 TI - PI3K signaling: A molecular pathway associated with acute hypophagic response during inflammatory challenges. AB - Energy balance has in the hypothalamus a central component of integration of food intake and energy expenditure. An accumulating body of evidence indicates that energy homeostasis is largely affected by inflammatory challenges. Severe undernutrition caused by exacerbated inflammatory response may lead to cachexia. On the other hand, prolonged low-grade inflammation such as that observed in obesity and metabolic syndrome, raises the risk for the development of diabetes and heart diseases. Changes in circulating insulin and cytokines such as leptin, interleukins and tumor necrosis factor, as well as changes in their action in the hypothalamus drive the inhibition of food consumption during inflammation. The molecular pathways associated with these responses have only started to be unraveled. One potential candidate is the PI3K signaling, an important player in distinct hypothalamic neurons that control food intake. This study presents an overview of the current knowledge about PI3K role on cytokines and insulin signaling in the hypothalamic regulation of feeding during inflammation. PMID- 27389882 TI - Measurements of radioactivity and dose assessments in some building materials in Bitlis, Turkey. AB - In this study, samples of perlite, pumice and Ahlat stones (Ignimbrite) extracted from mines in Bitlis and samples of other building materials produced in facilities in Bitlis were collected and analyzed. Activity concentrations of (226)Ra, (232)Th and (40)K in samples of building materials were measured using NaI detector (NaI(Tl)) with an efficiency of 24%. The radon measurements of building material samples were determined using CR-39 nuclear track detectors. (226)Ra, (232)Th and (40)K radioactivity concentrations ranged from (29.6+/-5.9 to 228.2+/-38.1Bq/kg), (10.8+/-5.4 to 95.5+/-26.1Bq/kg) and (249.3+/-124.7 to 2580.1+/-266.9Bq/kg), respectively. Radon concentration, radium equivalent activities, absorbed dose rate, excess lifetime cancer risk and the values of hazard indices were calculated for the measured samples to assess the radiation hazards arising from using those materials in the construction of dwellings. Radon concentration ranged between 89.2+/-12.0Bq/m(3) and 1141.0+/-225.0Bq/m(3). It was determined that Raeq values of samples conformed to world standards except for perlite and single samples of brick and Ahlat stone. Calculated values of absorbed dose rate ranged from 81.3+/-20.5 to 420.6+/-42.8nGy/h. ELCR values ranged from (1.8+/-0.3)*10(-3) to (9.0+/-1.0)*10(-3). All samples had ELCR values higher than the world average. The values of Hin and Hex varied from 0.35+/-0.11 to 1.78+/-0.18 and from 0.37+/-0.09 to 1.17+/-0.13, respectively. The results were compared with standard radioactivity values determined by international organizations and with similar studies. There would be a radiation risk for people living in buildings made of perlite, Ahlat-1 and Brick-3. PMID- 27389884 TI - Confronting the Legitimation Crisis: Introduction to Kernberg and Michels. PMID- 27389885 TI - Thoughts on the Present and Future of Psychoanalytic Education. AB - This paper originated in a series of dialogues between the authors over a period of approximately one year, focused on present problems (and possible solutions) in psychoanalytic education, internationally but particularly in the U.S. Both authors have been involved in psychoanalytic education and governance over many years and share a concern with where psychoanalysis presently stands and where it is going. They share the experience of being part of what today is a significant minority of psychoanalysts involved in academic pursuits, thus being situated at the boundary between psychoanalysis and university-based psychiatry as professions. Having been involved in the leadership of both psychoanalytic and psychiatric organizations, they share an interest in organizational theory, an additional joint interest influencing their approach to institutional aspects of psychoanalysis. Despite these commonalities, however, they have been identified as having differently shaded positions and views within psychoanalytic politics: Robert Michels, as relatively conservative regarding controversial issues in psychoanalytic institutional functioning and governance, and Otto Kernberg as inclined toward rapid change regarding these issues (Auchincloss and Michels 2003; Kernberg 2014). This difference determined a dynamic of particular interest in their dialogue: the extent to which mutual respect yet differing viewpoints might issue in an analysis and joint recommendations that might be of interest to the field. In what follows, their achievement in that direction is spelled out in some detail. PMID- 27389886 TI - Commentary on Kernberg and Michels. PMID- 27389887 TI - Commentary on Kernberg and Michels. PMID- 27389888 TI - Commentary on Kernberg and Michels. PMID- 27389889 TI - Commentary on Kernberg and Michels. PMID- 27389890 TI - Commentary on Kernberg and Michels. PMID- 27389891 TI - Response to Commentaries. PMID- 27389892 TI - Come Hither, American Psychoanalysis: Our Complex Multicultural America Needs What We Have to Offer. PMID- 27389893 TI - Is there a Usable Heidegger for Psychoanalysts? PMID- 27389903 TI - Overview, Control Strategies, and Lessons Learned in the CDC Response to the 2014 2016 Ebola Epidemic. AB - During 2014-2016, CDC, working with U.S. and international partners, mounted a concerted response to end the unprecedented epidemic of Ebola virus disease (Ebola) in West Africa. CDC's response, which was the largest in the agency's history, was directed simultaneously at controlling the epidemic in West Africa and strengthening preparedness for Ebola in the United States. Although experience in responding to approximately 20 Ebola outbreaks since 1976 had provided CDC and other international responders an understanding of the disease and how to stop its spread, the epidemic in West Africa presented new and formidable challenges. The initial response was slow and complicated for several reasons, including wide geographic spread of cases, poor public health and societal infrastructure, sociodemographic factors, local unfamiliarity with Ebola, and distrust of government and health care workers. In the United States, widespread public alarm erupted after Ebola cases were diagnosed in Dallas, Texas, and New York City, New York. CDC, in collaboration with its U.S. and international counterparts, applied proven public health strategies as well as innovative new approaches to help control the Ebola epidemic in West Africa and strengthen public health readiness in the United States. Lessons learned include the recognition that West African and other countries need effective systems to detect and stop infectious disease threats, the need for stronger international surge capacity for times when countries are overwhelmed by an outbreak, and the importance of improving infection prevention and control in health care settings. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27389905 TI - Future Papers. PMID- 27389904 TI - Wars2 is a determinant of angiogenesis. AB - Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases. PMID- 27389906 TI - Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of severe aortic stenosis: a meta-analysis of randomized trials. AB - AIMS: In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups. METHODS AND RESULTS: Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction [hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038] with homogeneity across all trials irrespective of TAVI device (Pinteraction = 0.306) and baseline risk (Pinteraction = 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access [0.80 (0.69-0.93); P = 0.004], but not transthoracic access [1.17 (0.88-1.56); P = 0.293] (Pinteraction = 0.024) and in female [0.68 (0.50-0.91); P = 0.010], but not male patients [0.99 (0.77-1.28); P = 0.952] (Pinteraction = 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR. CONCLUSION: Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females. PMID- 27389909 TI - Viral load kinetics of Zika virus in plasma, urine and saliva in a couple returning from Martinique, French West Indies. AB - While the rapid spread of Zika virus (ZIKV) in South America has been declared a public health emergency few data are available on the kinetics of the virus load and the specific antibodies in individual patients. This report describes the kinetics of ZIKV decay in the body compartments and the kinetics of anti ZIKV IgG and IgM of two people returning from Martinique, French West Indies. ZIKV remained detectable in the plasma for roughly 2 weeks indicating that mosquito control measures should be prolonged accordingly. Remarkably, their urine samples consistently tested positive for even longer. The antibodies responses were different between the two patients but for both the rapid onset of IgM allowed a diagnosis from the end of the first week. PMID- 27389907 TI - Catheter ablation in patients with persistent atrial fibrillation. AB - Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi centre trials. PMID- 27389910 TI - Immune-based guidance of foscarnet treatment duration in a transplant recipient with ganciclovir-resistant cytomegalovirus infection. AB - A lung and kidney transplant recipient underwent cytomegalovirus (CMV) primary infection with a UL97 mutation. Combined monitoring of viral load and CMV specific CD4 T-cells allowed reduction of treatment duration with foscarnet, and illustrates how knowledge on the individual immunocompetence towards CMV may be used to individualize duration of antiviral treatment. PMID- 27389911 TI - Collective Care: Multiple Caregivers and Multiple Care Recipients in Mexican American Families. AB - PURPOSE: Specific stressors associated with caregiving in Mexican American (MA) families are not well documented, yet caregiving issues are paramount because informal care for parents is central to their culture. Although MA families who band together to provide care for one member are not unique, the literature does not describe the phenomenon of collective caregiving, which may be widespread but unrecognized. This article describes these understudied families who are poorly served by contemporary health systems because their characteristics are unknown. DESIGN: Descriptive, multisite, longitudinal mixed-methods study of MA caregiving families. FINDINGS: We identified three types of collective caregivers: those providing care for multiple family members simultaneously, those providing care successively to several family members, and/or those needing care themselves during their caregiving of others. DISCUSSION AND CONCLUSIONS: Collective caregiving of MA elders warrants further investigation. IMPLICATIONS FOR PRACTICE: Exploration of collective caregiving may provide a foundation for tailored family interventions. PMID- 27389913 TI - Reforming the Match Process-Early Decision Plans and the Case for a Consortia Match. PMID- 27389912 TI - Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction. AB - Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk. PMID- 27389915 TI - Effects of Breast Milk and Vanilla Odors on Premature Neonates' Heart Rate and Blood Oxygen Saturation During and After Venipuncture. PMID- 27389914 TI - Distribution and Patterns of Industry-Related Payments to Oncologists in 2014. AB - BACKGROUND: Industry-physician collaboration is critical for anticancer therapeutic development, but financial relationships introduce conflicts of interest. We examined the specialty variation and context of physician payments and ownership interest among oncologists. METHODS: We performed a population based multivariable analysis of 2014 Open Payments reports of industry payments to US physicians matched to physician and practice data, including sex, specialty, practice location, and sole proprietor status. Payment data were aggregated per physician and compared by specialty (medical, radiation, surgical, and nononcology), and practice location linked with spending level (low, average, and high). Primary outcomes included likelihood, mean annual amount, and number of general payments. Secondary outcomes included likelihood of holding ownership interests and receipt of royalty/license payments. Estimates for each outcome were determined using multivariable models, including logistic regression for likelihood and linear regression with gamma distribution and log-link for value, adjusted for physician specialty, sex, sole proprietor status, and practice spending. All statistical tests were two-sided. RESULTS: In 2014, there were 883 438 physicians, including 22 712 oncologists, licensed to practice in the United States. Among oncology specialties, 52.4% to 63.0% of physicians received a general payment in 2014, totaling $76 million, $4 million, and $5 million to medical, radiation, and surgical oncology, respectively. The median annual per physician payment to medical oncologists was $632 (IQR = 136-2500), compared with $124 (IQR = 39-323) in radiation oncology and $250 (IQR = 84-1369) in surgical oncology. After controlling for physician and practice characteristics, oncologists were 1.09 to 1.75 times as likely to receive a general payment compared with nononcologists (overall P < 001). There was a 67.6% difference (95% confidence interval [CI] = 63.6 to 71.5, P < .001) in the mean annual value of payments between medical oncology and nononcology specialties (vs -92.7%, 95%CI = -100.2 to -85.0, P < .001] for radiation oncology). Medical and radiation oncologists were more likely to hold ownership interest (adjusted OR = 3.72, 95% CI = 3.22 to 4.27, and 2.27, 95% CI = 1.65 to 3.03, respectively, P < .001 both comparisons). CONCLUSIONS: In 2014, industry-oncologist financial relationships were common, and their impact on oncology practice should be further explored. PMID- 27389916 TI - Factors associated with end-of-life by home-visit nursing-care providers in Japan. AB - AIM: Home-visit nursing-care services in Japan are expected to provide home hospice services for older patients with non-cancer diseases. The aim of the present study was to examine factors that contribute to the provision of end-of life care by home-visit nursing-care providers in Japan. METHODS: The present retrospective study was carried out using nationally representative cross sectional data from the 2007, 2010, and 2013 Survey of Institutions and Establishments for Long-Term Care. A total of 138 008 randomly sampled home-visit nursing-care service users were included in this analysis. End-of-life care (study outcome) was defined as the provision of nursing-care within the last month of life. RESULTS: Of the 138 008 patients at home, 2280 (1.7%) received home-based nursing care within the last month of life, and end-of-life care was offered primarily to cancer patients (n = 1651; 72.4%). After accounting for patient characteristics, patients were more likely to receive end-of-life care when they used home-visit nursing-care providers that had a greater number of nursing staff or were located in a region with fewer hospital beds. CONCLUSIONS: Among home-visit nursing-care providers, the nursing staff ratio and the availability of hospital beds were related to the provision of end-of-life care. Home-visit nursing-care providers should establish specialist hospice care teams with enhanced staffing ratios to allow for the adequate provision of home-based end-of-life care. A community-based network between home-visit nursing-care providers and hospitals should also be established to attain an integrated end-of life care system for elderly populations in regions with more hospital beds. Geriatr Gerontol Int 2017; 17: 991-998. PMID- 27389917 TI - Incidence and differential characteristics of culture-negative fever following pancreas transplantation with anti-thymocyte globulin induction. AB - BACKGROUND: Limited data are available on the incidence and characteristics of culture-negative fever following pancreas transplantation (PTx) with anti thymocyte globulin (ATG) induction. Our study aims to better define the features of culture-negative fever, so it can be delineated from infectious fever, hopefully helping clinicians to guide antibiotic therapy in this high-risk patient population. METHODS: We performed a retrospective cohort study of postoperative fever among 198 consecutive patients undergoing PTx at our center between August 1, 2004 and December 31, 2014. Fever was classified as culture negative if there was neither a positive culture nor a documented clinical diagnosis of infection. RESULTS: Fever was identified in 113 patients; 66 were deemed to be infectious, 39 were culture-negative, and 8 were indeterminate. High body mass index of recipient (odds ratio 1.87, 95% confidence interval: 1.15 3.03, P = 0.011) was a significant factor associated with culture-negative fever in multivariate analysis. No patients with culture-negative fever were diagnosed with infiltrates or effusion on chest radiography. In addition, an increase in white blood cell count, C-reactive protein, and serum amylase was less prominent in culture-negative fever. Culture-negative fever developed most frequently at postoperative 7 or 14 days, showing a biphasic curve. CONCLUSION: Culture negative fever develops in a substantial proportion of patients early after PTx. The awareness of the possibility and clinical features of post-transplant culture negative fever might help clinicians to guide antibiotic therapy in this high risk patient population, especially following ATG induction and early steroid withdrawal. PMID- 27389919 TI - Motivational goals, group identifications, and psychosocial adjustment of returning migrants: The case of Jews returning to Russia. AB - The present study investigated the motivational goals, group identifications, and psychosocial adjustment of Jews who returned to Russia after emigrating from the republics of the Former Soviet Union to different countries (n = 151). To gain a deeper understanding of these returning migrants, their traits were compared with those of Jews living in Russia who did not emigrate (n = 935). Compared to locals, returnees reported a higher preference for the openness to change and self-enhancement values and a lower preference for the conservation values; there was no difference in the self-transcendence values. Returning migrants had a relatively weak affiliation with the home country: they had a weaker identification with the home country than with the country of emigration, their identification with Russians was weaker than that among Jews who did not emigrate from Russia, and their intention to emigrate (again) from Russia was greater than that among locals. However, the Jewish identification of returning migrants was similar to that of locals. The adjustment of returning migrants varied across different dimensions: their economic adjustment was better than that of locals; however, the interpersonal adjustment of returnees was less successful than among locals. PMID- 27389920 TI - Simultaneous observation of ligand-based fluorescence and phosphorescence within a magnesium-based CP/MOF at room temperature. AB - A highly thermally stable CP/MOF, comprised of Mg(2+) and H2EBTC(2-) with the formula of [Mg(H2EBTC)(DMF)2], emits dual band luminescence centered at 376 and 555 nm. The former is assigned to the fluorescence of H2EBTC(2-) and the latter with 1.63 MUs decay lifetime and large Stokes shifts corresponds to the phosphorescence of H2EBTC(2-). To the best of our knowledge, this is the first time the ligand-based phosphorescence in a CP/MOF without any heavy atom at room temperature has been observed. PMID- 27389918 TI - Impaired conditioned pain modulation in youth with functional abdominal pain. AB - Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. This study assessed CPM to evoked thermal pain in 140 youth (ages 10 17), 63 of whom had FAP and 77 of whom were healthy controls. Multilevel models demonstrated weaker CPM effects in youth with FAP than in healthy youth, as evident in slower within-person decreases in pain ratings during the conditioning phase. Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in youth with FAP were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth. PMID- 27389921 TI - Causal Inference Based on the Analysis of Events of Relations for Non-stationary Variables. AB - The main concept behind causality involves both statistical conditions and temporal relations. However, current approaches to causal inference, focusing on the probability vs. conditional probability contrast, are based on model functions or parametric estimation. These approaches are not appropriate when addressing non-stationary variables. In this work, we propose a causal inference approach based on the analysis of Events of Relations (CER). CER focuses on the temporal delay relation between cause and effect, and a binomial test is established to determine whether an "event of relation" with a non-zero delay is significantly different from one with zero delay. Because CER avoids parameter estimation of non-stationary variables per se, the method can be applied to both stationary and non-stationary signals. PMID- 27389923 TI - Corrigendum: Are viruses important in the plankton of highly turbid glacier-fed lakes? PMID- 27389922 TI - Effects of sex steroid hormones and their metabolites on neuronal injury caused by oxygen-glucose deprivation/reoxygenation in organotypic hippocampal slice cultures. AB - In this study, protective actions of the sex steroid hormones, progesterone, testosterone, and 17beta-estradiol, against oxygen-glucose deprivation (OGD)/reoxygenation-induced neuronal cell death were examined using rat organotypic hippocampal slice cultures. Progesterone, testosterone, and 17beta estradiol significantly attenuated neuronal cell death elicited by OGD/reoxygenation. While the neuroprotection conferred by progesterone was not affected by SU-10603, an inhibitor of cytochrome P45017alpha, finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone, partially reversed the neuroprotection induced by progesterone. The progesterone metabolite, allopregnanolone attenuated neuronal injury induced by OGD/reoxygenation. Pretreatment with letrozole, a cytochrome P450 aromatase inhibitor or 4-hydroxyphenyl-1-naphthol, a 17beta-hydroxysteroid dehydrogenase 2 inhibitor showed no effect on testosterone-mediated neuroprotection, while finasteride completely abolished the protective action of testosterone. Treatment with 5alpha-dihydrotestosterone significantly suppressed neuronal injury. Pretreatment with mifepristone, a progesterone receptor antagonist and hydroxyflutamid, an androgen receptor antagonist significantly diminished the neuroprotective effects of progesterone and testosterone, respectively. ICI182,780, an estrogen receptor antagonist, showed no effect on neuroprotection mediated by 17beta-estradiol. Pretreatment with actinomycin D or cycloheximide clearly abolished the neuroprotective effects of progesterone and testosterone, while actinomycin D and cycloheximide did not show any effect on neuroprotection mediated by 17beta-estradiol. Taken together, progesterone protects neurons via progesterone receptor-dependent genomic pathway, and allopregnanolone is involved in progesterone-mediated neuroprotection. Testosterone and its metabolite 5alpha dihydrotestosterone protect neurons via the genomic pathway of the androgen receptor. Metabolism of sex steroid hormones in the brain might complicate their protective actions in the brain. PMID- 27389924 TI - A novel anode comprised of C&N co-doped Co3O4 hollow nanofibres with excellent performance for lithium-ion batteries. AB - C&N co-doped Co3O4 hollow nanofibres are prepared by combining the electrospinning technique and the hydrothermal method, which show a high reversible capacity and excellent cycling stability as anode materials for Li-ion batteries. DFT calculations give a good explanation for the experimentally enhanced conductivity in C&N co-doped Co3O4 hollow nanofibres. PMID- 27389925 TI - Update on reconstructive options for nasal Mohs defects 1.5 cm or less. AB - PURPOSE OF REVIEW: The article reviews the current literature to provide an overview on contemporary reconstructive options for closure of Mohs defects of the nose that are 1.5 cm or less. RECENT FINDINGS: Although some of the techniques described in the literature are of historical importance only, others have undergone modification and metamorphosis to be broadly used in their contemporary form. Others are implemented in their original design, irrespective of relative age or multiple attempted adaptations. The increase in variable closure options available provides the surgeon with the ability to tailor reconstruction in such a way as to maximize form and function for the patient. SUMMARY: Here we will provide an update on the core techniques in terms of subtle modifications, expanded applications, and examination of outcomes as well as newly described closure techniques that may fill a certain niche in nasal reconstruction. PMID- 27389926 TI - Perceptions and Practices of Mass Bat Exposure Events in the Setting of Rabies Among U.S. Public Health Agencies. AB - Current guidelines in the setting of exposures to potentially rabid bats established by the Advisory Committee on Immunization Practices (ACIP) address post-exposure prophylaxis (PEP) administration in situations where a person may not be aware that a bite or direct contact has occurred and the bat is not available for diagnostic testing. These include instances when a bat is discovered in a room where a person awakens from sleep, is a child without an adult witness, has a mental disability or is intoxicated. The current ACIP guidelines, however, do not address PEP in the setting of multiple persons exposed to a bat or a bat colony, otherwise known as mass bat exposure (MBE) events. Due to a dearth of recommendations for response to these events, the reported reactions by public health agencies have varied widely. To address this perceived limitation, a survey of 45 state public health agencies was conducted to characterize prior experiences with MBE and practices to mitigate the public health risks. In general, most states (69% of the respondents) felt current ACIP guidelines were unclear in MBE scenarios. Thirty-three of the 45 states reported prior experience with MBE, receiving an average of 16.9 MBE calls per year and an investment of 106.7 person-hours annually on MBE investigations. PEP criteria, investigation methods and the experts recruited in MBE investigations varied between states. These dissimilarities could reflect differences in experience, scenario and resources. The lack of consistency in state responses to potential mass exposures to a highly fatal disease along with the large contingent of states dissatisfied with current ACIP guidance warrants the development of national guidelines in MBE settings. PMID- 27389928 TI - Relationship between resistin and mortality in maintenance hemodialysis patients. AB - AIMS: Determine the relationship of serum resistin level with outcome in maintenance hemodialysis (HD) patients. MATERIALS AND METHODS: This 49-month prospective study enrolled 101 HD patients and examined their clinical and demographic characteristics. RESULTS: 23 of the 87 patients in the cohort died. Survivors were younger, had higher body mass index, diastolic blood pressure, and serum levels of albumin, creatinine, potassium, and phosphate, and lower serum levels of resistin. Receiver operating characteristic (ROC) curve analysis indicated the optimal cut-off value of resistin for prediction of mortality was 127.4 ng/mL (area under the curve (AUC) = 0.667, p = 0.01). Cox proportional hazards regression analysis indicated that advanced age (p < 0.001) and resistin level above 127.4 ng/mL (p = 0.004) were associated with increased mortality risk. Albumin (p = 0.048), creatinine (p = 0.014), potassium (p = 0.023), calcium (p = 0.021), and phosphate (p = 0.001) were associated with decreased mortality risk. Multivariate regression analysis indicated that advanced age (adjusted hazard ratio (aHR) = 1.11, p < 0.0001) and elevated resistin concentration (aHR = 2.442, p = 0.0387) increased the risk for mortality. CONCLUSIONS: Advanced age and serum resistin concentration above 127.4 ng/mL are independent risk factors for mortality in patients undergoing maintenance HD. PMID- 27389929 TI - Generation and the role of dislocations in single-crystalline phase-change In2Se3 nanowires under electrical pulses. AB - We report the observation of the generation of dislocations in single-crystal phase-change In2Se3 nanowires under electrical pulses and the impact of these dislocations on electrical properties. Particularly, we correlated the atomic scale structural characteristics with local electrical resistance variations, by performing transmission electron microscopy and scanning Kelvin probe microscopy on the same nanowires. By coupling the experimental results with first-principles density functional theory calculations, we show that the immobile dislocations are generated via vacancy condensations. Importantly, these dislocations lead to several orders of magnitude increase in the electrical resistance, while maintaining the single crystallinity of the lattice. These results significantly advance the fundamental understanding of the structure-property relation in this phase-change material under transient electrical excitations. From a practical perspective, the significant increase in the electrical resistance, driven by the formation of dislocations, can be exploited as a new electronic state in the single-crystalline phase in this phase-change material. PMID- 27389930 TI - A fifth of acute pancreatitis cases are not diagnosed promptly, inquiry warns. PMID- 27389927 TI - Inflammation and epigenetic regulation in osteoarthritis. AB - Osteoarthritis (OA) was once defined as a non-inflammatory arthropathy, but it is now well-recognized that there is a major inflammatory component to this disease. In addition to synovial cells, articular chondrocytes and other cells of diarthrodial joints are also known to express inflammatory mediators. It has been proposed that targeting inflammation pathways could be a promising strategy to treat OA. There have been many reports of cross-talk between inflammation and epigenetic factors in cartilage. Specifically, inflammatory mediators have been shown to regulate levels of enzymes that catalyze changes in DNA methylation and histone structure, as well as alter levels of non-coding RNAs. In addition, expression levels of a number of these epigenetic factors have been shown to be altered in OA, thereby suggesting potential interplay between inflammation and epigenetics in this disease. This review provides information on inflammatory pathways in arthritis and summarizes published research on how epigenetic regulators are affected by inflammation in chondrocytes. Furthermore, we discuss data showing how altered expression of some of these epigenetic factors can induce either catabolic or anti-catabolic effects in response to inflammatory signals. A better understanding of how inflammation affects epigenetic factors in OA may provide us with novel therapeutic strategies to treat this condition. PMID- 27389931 TI - Re: The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell Carcinoma: N. W. Liu, J. D. Wren, E. Vertosick, J. K. Lee, N. E. Power, N. E. Benfante, S. Y. Kimm, M. S. Bains, D. D. Sjoberg, P. Russo and J. A. Coleman J Urol 2016;195:264-269. PMID- 27389932 TI - Optimizing the virological success of tenofovir DF/FTC/rilpivirine in HIV infected naive and virologically suppressed patients through strict clinical and virological selection. AB - BACKGROUND: Tenofovir DF/FTC/rilpivirine (TDF/FTC/RPV) is a single tablet regimen considered as safe and efficacious in HIV population as long as food requirements, concomitant PPI administration, and compromised antiviral activity have been carefully reviewed. We evaluated TDF/FTC/RPV in a real-life setting with focus on clinical and virological outcomes. METHODS: OCEAN II is a prospective, two-centre observational study. From September 2012 to December 2013, antiretroviral-naive patients with HIV RNA <100,000 copies/mL or wishing to switch for simplification were considered for TDF/FTC/RPV. A systematic review of potential obstacles to TDF/FTC/RPV administration was undertaken during a multidisciplinary meeting, including DNA genotyping to detect archived RPV and/or NRTI-associated resistance mutations if historical RNA resistance testing was lacking. RESULTS: TDF/FTC/RPV was considered for 480 patients, however was not offered to 194 patients (40%), mainly because of risk of insufficient virological efficacy, issues on adherence, patient refusal, meal constraint, or PPI therapy. A total of 286 patients (269 in maintenance; 17 ART-naive) received TDF/FTC/RPV. After a median follow-up of 30 months, virological failure occurred in five patients (1.7%) without the emergence of resistance mutations. Discontinuation of TDF/FTC/RPV occurred in 98 patients, due to adverse events in 43 patients (44%) and non-safety reasons in 55 patients (56%). No grade three-fourth adverse events occurred. CONCLUSION: In this real-life experience, cohort consisting primarily of virologically suppressed patients, TDF/FTC/RPV usually maintained virologic suppression. Discontinuation of therapy because of intolerability was due to mild adverse events. Strict clinical and virological screening probably explained the low rate of virological failure. PMID- 27389934 TI - Reply. PMID- 27389933 TI - Percentage of Peripheral CD19+CD24hiCD38hi Regulatory B Cells in Neonatal Sepsis Patients and Its Functional Implication. AB - BACKGROUND As a major cause of mortality in neonates, neonatal sepsis is often accompanied by immune dysfunctions, which are frequently caused by dysregulated T cell sub-populations. The role of regulatory B cells in neonatal sepsis, however, remains unknown. Therefore, this study investigated the percentage and functional variation of CD19+CD24hiCD38hi regulatory B cells in peripheral blood of neonatal sepsis patients in an attempt to elucidate the role of these regulatory B cells in pathogenesis of sepsis. MATERIAL AND METHODS Flow cytometry was used to quantify the percentage of CD19+CD24hiCD38hi regulatory B cells from peripheral blood samples. The correlation between B cell percentage and C reactive protein (CRP) level was analyzed. Secretion level of interleukin-10 (IL-10) and effects on the proliferation of naive CD4+ T cells were further analyzed. RESULTS The percentage of CD19+CD24hiCD38hi regulatory B cells in neonatal sepsis patients was significantly higher compared to healthy controls (p<0.05), and was positively correlated with serum CRP level. The percentage of IL-10+ CD19+CD24hiCD38hi regulatory B cells was also higher in sepsis patients, and also had more potent inhibition on naive CD4+ T cells (p<0.01). CONCLUSIONS The elevation of CD19+CD24hiCD38hi regulatory B cells in neonatal sepsis can inhibit body immune function and thus may participate in the pathogenesis of sepsis. PMID- 27389935 TI - Bifunctional Ligands for Inhibition of Tight-Binding Protein-Protein Interactions. AB - The acknowledged potential of small-molecule therapeutics targeting disease related protein-protein interactions (PPIs) has promoted active research in this field. The strategy of using small molecule inhibitors (SMIs) to fight strong (tight-binding) PPIs tends to fall short due to the flat and wide interfaces of PPIs. Here we propose a biligand approach for disruption of strong PPIs. The potential of this approach was realized for disruption of the tight-binding (KD = 100 pM) tetrameric holoenzyme of cAMP-dependent protein kinase (PKA). Supported by X-ray analysis of cocrystals, bifunctional inhibitors (ARC-inhibitors) were constructed that simultaneously associated with both the ATP-pocket and the PPI interface area of the catalytic subunit of PKA (PKAc). Bifunctional inhibitor ARC 1411, possessing a KD value of 3 pM toward PKAc, induced the dissociation of the PKA holoenzyme with a low-nanomolar IC50, whereas the ATP-competitive inhibitor H89 bound to the PKA holoenzyme without disruption of the protein tetramer. PMID- 27389936 TI - Position and Course of Facial Nerve and Postoperative Facial Nerve Results in Vestibular Schwannoma Microsurgery. AB - OBJECTIVE: To investigate the variation in the position and course of the facial nerve (FN) in patients undergoing vestibular schwannoma (VS) microsurgery by the keyhole retrosigmoid approach and the relationship between FN position and postoperative facial results. METHODS: The series consists of 100 patients who underwent VS microsurgery during a 5-year period in whom the position and course of the FN could be confirmed by direct stimulation. The course of the FN was classified into 4 patterns according to its position: anterior (ventral) surface of the tumor (A), anterior-superior (AS), anterior-inferior (AI), and dorsal (D). RESULTS: The distribution of patterns was as follows: AS in 48 cases, A in 31, AI in 21, and D in zero. For tumors <1.5 cm, the AS pattern was most common (68.4%). For tumors >=1.5 cm, the proportion of A and AI positions increased (31.4% and 25.5%). Significant differences were observed between position and course patterns of the FN and postoperative nerve results. Patients with AS and AI patterns had better House-Brackmann FN function compared with patients with the A pattern (P < 0.05). Moreover, in tumors >3.0 cm, the FN tended to adhere strongly to the tumor capsule, and postoperative facial deficits were more frequent (P < 0.05). CONCLUSIONS: The AS pattern was most common for smaller VSs. The A position and course and adhesion of the FN to the tumor capsule were the 2 factors most strongly associated with worse postoperative FN result. PMID- 27389937 TI - One-Stage Resection of a Giant Petrous Bone Osteoma Associated with a Contiguous Meningioma Via a Modified Anterior Transpetrous Approach. AB - BACKGROUND: In addition to the previous 5 cases of skull base osteoma with radiologic information reported in the English literature, this is the sixth case report of this rare disease. CASE DESCRIPTION: This is the first report of a skull base osteoma with concurrent intracranial tumors. CONCLUSION: A satisfactory 1-stage resection of the 2 contiguous lesions via a modified anterior transpetrous approach was performed. PMID- 27389938 TI - Short- and Long-Term Outcome of Microscopic Lumbar Spine Surgery in Patients with Predominant Back or Predominant Leg Pain. AB - OBJECTIVE: This study assessed whether predominant back pain (pBP) represents a negative outcome predictor in patients undergoing microscopic spine surgery without fusion for a lumbar disc herniation (LDH) or spinal stenosis (LSS). METHODS: Retrospective analysis of prospectively collected data on consecutive patients with LDH or LSS at 2 centers. Patients with visual analog scale (VAS) back pain >=VAS leg pain were assigned to the pBP group, and compared with patients with predominant VAS leg pain (pLP). Outcome measures included the Roland-Morris Disability Index (RMDI), Oswestry Disability Index (ODI), health related quality of life measures, Short-Form (SF)-12 Physical Component Summary (PCS), and EuroQol (EQ-5D) index at 3 days, 6 weeks (W6), 6 months, and 1 year postoperatively. RESULTS: A total of 325 patients (154 [47.4%] with pBP and 171 [52.6%] with pLP) were included. Patients with pBP were about 6 years older and more often had LSS. There was no significant difference between the group means of the RMDI, ODI, SF-12 PCS, or EQ-5D at any postoperative time point. The most improvement was observed until the W6 follow-up with little or no improvement thereafter up to 1 year postoperatively. Patients with pBP were as likely as patients with pLP to be W6 responders on the RMDI (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.38-2.16; P = 0.831), ODI (OR, 1.00; 95% CI 0.52-1.92; P = 0.996), SF-12 PCS (OR, 1.09; 95% CI 0.58-2.04; P = 0.791), and EQ-5D (OR, 0.62; 95% CI 0.32-1.21; P = 0.164). Disease-specific subgroup analyses confirmed the results. CONCLUSIONS: The present data suggest that patients with pBP have comparable functional and health-related quality of life outcomes after surgery for LDH or LSS with those of patients with pLP. PMID- 27389939 TI - An Evidence-Based Stepwise Surgical Approach to Cervical Spondylotic Myelopathy: A Narrative Review of the Current Literature. AB - OBJECTIVE: Cervical spondylotic myelopathy (CSM) is the most common progressive degenerative disease of the spine in the geriatric population. The aim of the current review is to provide an evidence-based stepwise surgical approach to CSM according to the recent literature. METHODS: We searched for evidence regarding the surgical approach to CSM in medical databases with articles dated from 1985 to 2016. RESULTS: In patients with effective cervical lordosis (fewer than 3 levels of ventral disease), anterior cervical discectomy and fusion (ACDF) or arthroplasty is preferred. Patients with more than 3 levels of compression are generally treated by laminoplasty, especially with preserved lordotic curvature. In patients with straightened spine who have less than 3 involved levels, ACDF with a plate is recommended, whereas patients with more than 3 involved levels with instability should undergo posterior decompression and fusion. In young patients who have a stable cervical spine, laminoplasty is recommended and in old patients with ankylosed spine, only laminectomy should be performed. Patients with mild cervical kyphosis (kyphotic angle <=10 degrees ) should be managed in the same way as patients with straightened spine. However, in severe kyphosis, cervical traction is recommended. If the kyphosis is reducible, further posterior decompression and fusion is adequate. In patients with irreducible kyphosis, if the number of involved levels is less than 2, ACDF is adequate, but if it is more than 2 levels, anterior cervical corpectomy and fusion should be performed using cervical magnetic resonance imaging for evaluation of the patency of the subarachnoid space (SAS). With patent SAS, only posterior fusion is adequate, whereas in closed SAS, posterior decompression with posterior fusion is required. These approaches are based on the most recent evidence. CONCLUSIONS: This article provides a stepwise evidence-based surgical approach for the management and treatment of patients with CSM. PMID- 27389940 TI - A Frameless Stereotactic Implantation Technique for Depth Electrodes in Refractory Epilepsy Using Intraoperative Magnetic Resonance Imaging. AB - OBJECTIVE: Various complex techniques for depth electrode insertion in refractory epilepsy using preoperative imaging have been investigated. We evaluated a simple, accurate, cost-effective, and timesaving method using intraoperative magnetic resonance imaging (MRI). METHODS: A neuronavigation-guided insertion tube attached to bone facilitated the placement of stereotactic percutaneous drill holes, bolt implantation, and frameless stereotactic insertion of depth electrodes. Image registration was carried out by head coil fiducials with trajectory planning and intraoperative electrode correction. RESULTS: In 6 patients with refractory epilepsy (3 women and 3 men; mean age, 30.0 years; range, 20-37 years), 58 depth electrodes (9-11 per patient) were placed. The mean length of the inserted electrodes was 37.3 mm +/- 8.8 (mean +/- SD) (range, 22.1 84.4 mm). The overall target point accuracy was 3.2 mm +/- 2.2 (range, 0-8.6 mm), which was significantly different from the overall entry point accuracy of 1.4 mm +/- 1.2 (P < 0.0001). All electrodes functioned perfectly, enabling high-quality stereo-electroencephalography recordings over a period of 7.3 days +/- 0.5 (range, 7-8 days). The mean implantation time for 9-11 electrodes per patient was 115 minutes +/- 36.3 (range, 75-160 minutes; 12 minutes for 1 electrode on average) including the intraoperative MRI (T1 three-dimensional magnetization prepared rapid acquisition gradient echo, T2, and diffusion tensor imaging). There was no hemorrhage, infection, or neurologic deficit related to the procedure. CONCLUSIONS: Our frameless technique of depth electrode insertion using intraoperative MRI guidance is an accurate, reliable, cost-effective, and timesaving method for stereo-electroencephalography. PMID- 27389941 TI - Cervical Myelopathy Caused by Bilateral Laminar Cleft of the Axis: Case Report and Review of Literature. AB - BACKGROUND: Cervical myelopathy due to bilateral laminar cleft of the axis is extremely rare, and few cases have been previously reported. However, its treatment is relatively simple. Surgical removal of the anomalous bony structure compromising the spinal canal can sufficiently achieve a good outcome. CASE DESCRIPTION: A 56-year-old man presented with a 2-year history of stiffness of the left upper and lower extremities. Cervical spine computed tomography showed a bony cleft at both laminae of the posterior arch of the axis, with obvious cord compression on magnetic resonance imaging. Although absence of right pedicle and spina bifida of C7 were also detected, there was no cord compression at this level. The patient underwent surgical removal of the anomalous laminar cleft and the spinous process of the axis. Postoperatively, he improved rapidly and was discharged on the seventh postoperative day. He was asymptomatic at the 3-year follow-up. After surgery, the preoperative myelopathy status was much improved. About 7 years after surgery, radiographs showed no kyphosis and instability. CONCLUSION: Invaginated bilateral laminar cleft of the axis is a rare cause of cervical myelopathy. The findings in our case should broaden the radiographic differential diagnosis in patients with cervical myelopathy. Surgical removal is an appropriate and simple treatment for this patient, resulting in a satisfactory outcome. PMID- 27389942 TI - Protamine Reduces Bleeding Complications without Increasing the Risk of Stroke after Carotid Endarterectomy: A Meta-analysis. AB - OBJECTIVES: The aim was to evaluate the safety and efficacy of heparin reversal with protamine after completion of carotid endarterectomy (CEA), summarising the available data from both randomised and non-randomised studies. METHODS: The study was a meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated for the outcomes of stroke and wound haematoma among patients receiving or not receiving protamine after CEA. Meta-regression analysis was performed to examine whether the documented differences were modified by potentially meaningful patient related or procedure related predictors, namely publication year, general anesthesia used, number of patients treated, mean age (years), males, neurological symptoms, use of patch, and use of shunt. RESULTS: Seven studies were included in the meta-analysis reporting on 3,817 patients receiving protamine after CEA and 6,070 patients not receiving protamine for heparin reversal. Only one study was randomised. A statistically significant reduction in wound haematoma requiring re-operation was recorded after heparin reversal with protamine in patients undergoing CEA (OR, 0.42, 95% CI, 0.22-0.80, p = .008). In contrast, no significant difference was observed in stroke rates between groups of patients that received and did not receive protamine (OR, 0.71, 95% CI, 0.49-1.03, p = .07). Meta-regression analysis did not reveal any significant effect mediated by the modifiers examined. CONCLUSION: On the basis of the available data, heparin reversal with protamine seems to reduce the risk of wound haematoma, without increasing the risk of procedural stroke. However, taking into account the limitations of the analysis, further studies are needed to increase the level of evidence provided by the current meta-analysis. PMID- 27389943 TI - A Comparison of Accuracy of Image- versus Hardware-based Tracking Technologies in 3D Fusion in Aortic Endografting. AB - OBJECTIVES: Fusion of three-dimensional (3D) computed tomography and intraoperative two-dimensional imaging in endovascular surgery relies on manual rigid co-registration of bony landmarks and tracking of hardware to provide a 3D overlay (hardware-based tracking, HWT). An alternative technique (image-based tracking, IMT) uses image recognition to register and place the fusion mask. We present preliminary experience with an agnostic fusion technology that uses IMT, with the aim of comparing the accuracy of overlay for this technology with HWT. METHOD: Data were collected prospectively for 12 patients. All devices were deployed using both IMT and HWT fusion assistance concurrently. Postoperative analysis of both systems was performed by three blinded expert observers, from selected time-points during the procedures, using the displacement of fusion rings, the overlay of vascular markings and the true ostia of renal arteries. The Mean overlay error and the deviation from mean error was derived using image analysis software. Comparison of the mean overlay error was made between IMT and HWT. The validity of the point-picking technique was assessed. RESULTS: IMT was successful in all of the first 12 cases, whereas technical learning curve challenges thwarted HWT in four cases. When independent operators assessed the degree of accuracy of the overlay, the median error for IMT was 3.9 mm (IQR 2.89 6.24, max 9.5) versus 8.64 mm (IQR 6.1-16.8, max 24.5) for HWT (p = .001). Variance per observer was 0.69 mm(2) and 95% limit of agreement +/-1.63. CONCLUSION: In this preliminary study, the error of magnitude of displacement from the "true anatomy" during image overlay in IMT was less than for HWT. This confirms that ongoing manual re-registration, as recommended by the manufacturer, should be performed for HWT systems to maintain accuracy. The error in position of the fusion markers for IMT was consistent, thus may be considered predictable. PMID- 27389944 TI - Mechanochemical removal of carbamazepine. AB - Carbamazepine (CBZ) is a drug used for treating epilepsy, neuropathic pain, schizophrenia and bipolar disorder. Its widespread use is indicated by its listing in the WHO's Model List of Essential Medicines. The accumulation of CBZ in various environmental compartments, specifically in crops irrigated with treated effluent or grown on soils containing biosolids, is often reported. Being a persistent PPCP (a pharmaceutical and personal care product), developing procedures to remove CBZ is of great importance. In the present study, the breakdown of CBZ by surface reactions in contact with various minerals was attempted. While Al-montmorillonite enhanced CBZ disappearance without the need to apply mechanical force, the efficiency of magnetite in enhancing the disappearance increased considerably upon applying such force. Ball milling with magnetite generated a virtually complete disappearance of CBZ (~94% of the applied CBZ disappeared after milling for 30 min). HPLC, LC/MS and FTIR were employed in an attempt to elucidate the rate of disappearance and degradation mechanisms of CBZ. A small amount of the hydrolysis product iminostilbene was identified by LC/MS and the breaking off of carbamic acid from the fused rings skeleton of CBZ was indicated by FTIR spectroscopy, confirming the formation of iminostilbene. PMID- 27389945 TI - Utilizing the partitioning properties of silicone for the passive sampling of polychlorinated biphenyls (PCBs) in indoor air. AB - The former use of polychlorinated biphenyls (PCBs) in construction materials can lead to elevated indoor air concentrations. We studied the partitioning of PCB congeners between indoor air and silicone with a view to establish passive sampling of PCBs. The release of PCB congeners from silicone followed first order kinetics and confirmed air-side rate-limited mass transfer. Logarithmic elimination rate constants decreased linearly with the logKOA values of the PCB congeners, but varied in a non-linear way with air velocity. Linear uptake of PCBs was found for silicone disks (0.5 mm thickness) in a petri dish, while PCBs reached equilibrium in silicone-coated paper sheets (0.001 mm silicone on each side) exposed to indoor air for 1-2 weeks. The ratios of equilibrium concentrations in silicone and conventionally measured air concentrations were roughly comparable with silicone-air partition coefficients, but further research is required for the determination of silicone-air partition coefficients. Avoiding performance reference compounds (PRCs) because of the indoor setting, the two formats were calibrated against conventional active measurements. Comparisons of air concentrations derived from active and kinetic passive sampling showed a divergence by factors of 2.4 and 2.0 (median values) for the petri dishes and the silicone-coated paper, respectively. With promising results for sensitivity and precision, the calibration of kinetic passive samplers remains the main challenge and will need suitable, non-hazardous PRCs. Equilibrium sampling indicated promising alternatives. PMID- 27389946 TI - Gait parameters of people with diabetes-related neuropathic plantar foot ulcers. AB - BACKGROUND: Foot ulceration associated with diabetic peripheral neuropathy is a global concern. Biomechanical investigation allows the identification of gait abnormalities that may adversely affect ulcer healing. The objective of this case control study was to compare the gait parameters of cases with diabetes-related foot ulcers to controls. METHODS: Three-dimensional movement analyses were performed on 21 people with diabetes-related neuropathic plantar foot ulcers (cases), 69 people with diabetes without a foot ulcer history (diabetes controls) and 56 healthy controls. Outcome data were reported as mean differences, 95% confidence intervals and Cohen's d effect sizes. Binary logistic regressions were used to adjust for age, sex and body mass index. FINDINGS: People with foot ulcers had a smaller plantar flexion (Cohen's d=-0.6 vs. diabetes controls and d= 0.8 vs. healthy controls), knee flexion (d=-0.6 vs. diabetes controls and d=-1.0 vs. healthy controls) and pelvic obliquity (d=-0.9 vs. diabetes controls and d= 0.7 vs. healthy controls) (all P<0.05). They also had a significantly greater range of anterior-posterior ground reaction force (d=1.0 vs. diabetes controls and d=1.7 vs. healthy controls) and total vertical ground reaction force (d=0.9 vs. diabetes controls and d=1.1 vs. healthy controls) and significantly slower walking speed and smaller step length compared to controls (all P<0.05). INTERPRETATION: People with plantar foot ulcers have considerably different gait parameters to controls. Whether the observed gait parameters contributed to the ulcer development or are a response to the ulcer is currently unclear and needs further investigation. PMID- 27389958 TI - Establishment of X chromosome inactivation and epigenomic features of the inactive X depend on cellular contexts. AB - X chromosome inactivation (XCI) is an essential epigenetic process that ensures X linked gene dosage equilibrium between sexes in mammals. XCI is dynamically regulated during development in a manner that is intimately linked to differentiation. Numerous studies, which we review here, have explored the dynamics of X inactivation and reactivation in the context of development, differentiation and diseases, and the phenotypic and molecular link between the inactive status, and the cellular context. Here, we also assess whether XCI is a uniform mechanism in mammals by analyzing epigenetic signatures of the inactive X (Xi) in different species and cellular contexts. It appears that the timing of XCI and the epigenetic signature of the inactive X greatly vary between species. Surprisingly, even within a given species, various Xi configurations are found across cellular states. We discuss possible mechanisms underlying these variations, and how they might influence the fate of the Xi. PMID- 27389959 TI - The vestibular body: Vestibular contributions to bodily representations. AB - Vestibular signals are integrated with signals from other sensory modalities. This convergence could reflect an important mechanism for maintaining the perception of the body. Here we review the current literature in order to develop a framework for understanding how the vestibular system contributes to body representation. According to recent models, we distinguish between three processes for body representation, and we look at whether vestibular signals might influence each process. These are (i) somatosensation, the primary sensory processing of somatic stimuli, (ii) somatoperception, the processes of constructing percepts and experiences of somatic objects and events and (iii) somatorepresentation, the knowledge about the body as a physical object in the world. Vestibular signals appear to contribute to all three levels in this model of body processing. Thus, the traditional view of the vestibular system as a low level, dedicated orienting module tends to underestimate the pervasive role of vestibular input in bodily self-awareness. PMID- 27389960 TI - Validation of the Injustice Experiences Questionnaire in a heterogeneous trauma sample. AB - PURPOSE/OBJECTIVE: A recent study by Trost et al. (2015) investigated the influence of perceived injustice-reflecting appraisals of the severity and irreparability of loss following injury, blame, and unfairness-on physical and psychological outcomes in a sample of patients 12 months after sustaining a traumatic injury. This brief report examines the psychometric properties of the Injustice Experiences Questionnaire (IEQ) using the previous sample from Trost et al. (2015) with added trauma patients (total N = 206). RESEARCH METHOD/DESIGN: Primary analyses included confirmatory and exploratory factor analyses to validate the measurement model of the IEQ in patients 12 months after traumatic injury. Reliability analyses were conducted and construct validity was assessed by examining associations between the IEQ and other pain-related, psychological, and health-related outcome variables of interest. RESULTS: Results replicated both one- and two-factor structures from past research, with a high factor correlation in confirmatory factor analyses and cross-loadings in exploratory factor analysis. Item characteristics analysis demonstrated overall strong internal consistency (alpha = .95). In addition, significant associations with psychosocial variables provide additional construct validity in regards to related outcomes. CONCLUSION/IMPLICATIONS: The IEQ shows strong psychometric properties and is suitable for use in a sample of diverse traumatic injury. However, results suggest the use of a one-factor model for the IEQ in this sample. Future trauma and rehabilitation research can use the IEQ to explore how injustice perceptions related to traumatic injury can prospectively influence physical and psychological outcomes. (PsycINFO Database Record PMID- 27389962 TI - Immature, but Not Mature, Dendritic Cells Are More Often Present in Aggressive Periodontitis Than Chronic Periodontitis: An Immunohistochemical Study. AB - BACKGROUND: Dendritic cells (DCs) form a key link between innate and adaptive immune responses. The aim of this study is to analyze presence and distribution of immature (im) and mature (m) DCs in gingival tissue samples obtained from patients diagnosed with aggressive periodontitis (AgP), chronic periodontitis (CP), and clinically healthy periodontium (control group). METHODS: Gingival tissue samples obtained from patients with: 1) AgP (aged <35 years); 2) CP (aged >=35 years); and 3) control group (aged >18 years) (n = 10 per group) were collected. Two-way analysis of variance and posterior Fisher least significant difference test were used to observe differences between the means of cells positively marked for imDC (S100, CD1a, and CD207) and mDC (CD208) immunomarkers. RESULTS: imDCs were more numerous in AgP than CP and control groups, being statistically significant only for S100+ cells. Conversely, mDCs were visualized in higher numbers in CP than AgP and control groups (both P <0.05). Considering frequency of immunostained cells, the number of S100+ cells was greater than CD207+ and CD1a+ cells, followed by a lesser number of CD208+ cells, in all groups. CONCLUSIONS: Considering that the ability of DCs to regulate immunity is dependent on DC maturation, results suggest that predominance of imDCs appears to be involved in AgP pathogenesis, probably due to lack of ability to induce immune cell activation. Further studies are necessary to elucidate the role of DC maturation in regulating immune responses in periodontal disease. PMID- 27389961 TI - IL-21 and T Cell Differentiation: Consider the Context. AB - Accumulating studies demonstrate that IL-21 modulates the differentiation of various CD4 and CD8 T cell subsets and provide insights into the underlying cellular and molecular processes that are influenced by this cytokine. Intriguingly, the effects of IL-21 on T cells can be complex and vary depending on the experimental system used. We review our current understanding of the roles of IL-21 in the generation of phenotypically distinct CD4 and CD8 T cell populations and discuss the potential environmental cues, cellular factors, and molecular mediators that impact the actions of IL-21. We propose that IL-21 acts in a context-dependent manner to accentuate T cell subset development. PMID- 27389963 TI - Efficacy of 0.12% Chlorhexidine Gluconate for Non-Surgical Treatment of Peri Implant Mucositis. AB - BACKGROUND: Because peri-implant mucositis may progress to peri-implantitis, effective treatment resulting in resolution of inflammation could prevent peri implantitis. Current treatment protocols for this condition are still unpredictable. The purpose of this study is to analyze efficacy of non-surgical treatment for patients with peri-implant mucositis during a 6-month follow-up period. METHODS: This controlled, randomized, double-masked clinical trial included 37 patients diagnosed with peri-implant mucositis, randomly assigned into test group (basic periodontal therapy + 0.12% chlorhexidine) with 61 implants; and control group (basic periodontal therapy + placebo) with 58 implants. Therapy consisted of adaptation of the full-mouth scaling and root planing protocol. Clinical parameters of visible plaque index (VPI), gingival bleeding index (GBI), probing depth (PD), and bleeding on probing (BOP) were measured in implants and were evaluated at baseline and at 1, 3, and 6 months post-therapy. Data were analyzed using the split-plot analysis of variance and chi2 tests with a significance level of 5%. RESULTS: Intragroup analysis showed that VPI, GBI, PD, and BOP presented statistically significant improvements compared with baseline. No statistically significant differences were found between the test and control groups at any time. CONCLUSIONS: Both isolated mechanical therapy and its association with 0.12% chlorhexidine mouthwash reduced peri-implant mucositis. Therefore, 0.12% of chlorhexidine was not more effective than placebo. PMID- 27389964 TI - Association Among Periodontitis and the Use of Crack Cocaine and Other Illicit Drugs. AB - BACKGROUND: Crack cocaine can alter functions related to the immune system and exert a negative influence on progression and severity of periodontitis. The aim of this study is to compare periodontal status between crack cocaine users and crack cocaine non-users and investigate the association between crack cocaine and periodontitis after adjustments for confounding variables. METHODS: This cross sectional study evaluated 106 individuals exposed to crack cocaine and 106 never exposed, matched for age, sex, and tobacco use. An examiner determined visible plaque index (VPI), marginal bleeding index, supragingival dental calculus, probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Logistic regression was used to model associations between crack cocaine and periodontitis (at least three sites with CAL >4 mm and at least two sites with PD >3 mm, not in the same site or tooth). RESULTS: Prevalence of periodontitis among crack non-users and crack users was 20.8% and 43.4%, respectively. Crack users had greater VPI, BOP, PD >=3 mm, and CAL >=4 mm than crack non-users. Periodontitis was associated with age >24 years, schooling <=8 years, smoking, moderate/heavy alcohol use, and plaque rate >=41%. Crack users had an approximately three-fold greater chance (odds ratio: 3.44; 95% confidence interval: 1.51 to 7.86) of periodontitis than non-users. CONCLUSION: Occurrence of periodontitis, visible plaque, and gingival bleeding was significantly higher among crack users, and crack use was associated with occurrence of periodontitis. PMID- 27389965 TI - Countering the Segregation of Transition-Metal Ions in LiMn1/3 Co1/3 Ni1/3 O2 Cathode for Ultralong Life and High-Energy Li-Ion Batteries. AB - High-voltage layered lithium transition-metal oxides are very promising cathodes for high-energy Li-ion batteries. However, these materials often suffer from a fast degradation of cycling stability due to structural evolutions. It seriously impedes the large-scale application of layered lithium transition-metal oxides. In this work, an ultralong life LiMn1/3 Co1/3 Ni1/3 O2 microspherical cathode is prepared by constructing an Mn-rich surface. Its capacity retention ratio at 700 mA g(-1) is as large as 92.9% after 600 cycles. The energy dispersive X-ray maps of electrodes after numerous cycles demonstrate that the ultralong life of the as prepared cathode is attributed to the mitigation of TM-ions segregation. Additionally, it is discovered that layered lithium transition-metal oxide cathodes with an Mn-rich surface can mitigate the segregation of TM ions and the corrosion of active materials. This study provides a new strategy to counter the segregation of TM ions in layered lithium transition-metal oxides and will help to the design and development of high-energy cathodes with ultralong life. PMID- 27389966 TI - Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. AB - Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesized that keystone genes from the entire GH complement of Salmonella are required to degrade glycans to change infection. This study determined that GHs recognize the terminal monosaccharides (N acetylneuraminic acid (Neu5Ac), galactose, mannose, and fucose) and significantly (p < 0.05) alter infection. During infection, Salmonella used its two GHs sialidase nanH and amylase malS for internalization by targeting different glycan structures. The host glycans were altered during Salmonella association via the induction of N-glycan biosynthesis pathways leading to modification of host glycans by increasing fucosylation and mannose content, while decreasing sialylation. Gene expression analysis indicated that the host cell responded by regulating more than 50 genes resulting in remodeled glycans in response to Salmonella treatment. This study established the glycan structures on colonic epithelial cells, determined that Salmonella required two keystone GHs for internalization, and left remodeled host glycans as a result of infection. These data indicate that microbial GHs are undiscovered virulence factors. PMID- 27389967 TI - [Breast asymmetry of the teenager and the young adult. Stability of the result in time. About 144 patients]. AB - INTRODUCTION: Breast asymmetry is defined by a difference in breast shape and/or volume. The goal of this study was to assess the stability of the surgical results and to highlight predictive factors for deterioration in results. MATERIALS AND METHODS: This retrospective and monocentric study included all patients presenting constitutional isolated asymmetry, Poland's syndrome, asymmetric tuberous breast or pectus excavatum treated between 1980 and 2015. RESULTS: The statistical analysis included 144 patients and contained two parts. The first analysis compared patients with or without breast implant. Results were significant only for symmetry of shape, with better outcomes without breast implant (P=0.0170). The second analysis compared the subgroups of patients with breast asymmetry, according to the etiology. Patients with tuberous breasts and constitutional isolated asymmetry have been compared. We found a significant difference only regarding the long-term results (P=0.0091). Patients with tuberous breasts had deteriorating in results over time. Patients with Poland's syndrome, compared to patients with constitutional isolated asymmetry, had significantly less good results for symmetry of volume, of shape, of areola, and for early results (P<0.025). Concerning patients with pectus excavatum, the early and long-term results and the stability were good for most patients. CONCLUSION: Better results have been obtained with similar surgical procedures on both sides. Predictive factors for instability of results were the use of unilateral breast implant, weight variations, pregnancies and breast-feeding, the use of hormonal treatments, ageing and tuberous malformation. PMID- 27389968 TI - Failure to Disclose Conflicts of Interest. PMID- 27389970 TI - A Short Synthesis of Aphanamol I in Both Racemic and Enantiopure Forms. AB - A short synthesis of the biologically active sesquiterpene natural product (+) aphanamol I in both racemic and enantiopure forms is reported. Key steps include: a catalytic enantioselective conjugate addition, an oxidative radical cyclization, and a ring-expanding Claisen rearrangement. PMID- 27389969 TI - Podoplanin associates with adverse postoperative prognosis of patients with clear cell renal cell carcinoma. AB - Podoplanin, a transmembrane sialomucin-like glycoprotein, was recently shown to be involved in tumor progression and metastasis, and its potential role in facilitating platelet-based tumor embolization and promigratory phenotype of cancer cells was also demonstrated. In this study, we assessed the clinical significance of tumoral podoplanin expression in 295 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays and analyzing the staining intensity. Univariate analysis suggested an adverse prognostic effect of high tumoral podoplanin expression on patients' overall survival (OS) and recurrence-free survival (RFS) (P < 0.001 for both). In the multivariate analysis, high tumoral podoplanin expression (using staining intensity as either a continuous or dichotomous variable) was still an independent adverse prognostic factor for patient survival (OS, P < 0.001, RFS, P < 0.001 for continuous; OS, P < 0.001, RFS, P = 0.002 for dichotomous). Moreover, stratified analysis identified a higher prognostic power in the intermediate/high risk patient groups. After utilizing those parameters in the validated multivariate analysis, two nomograms were constructed to predict ccRCC patients' OS and RFS (c-index 0.815 and 0.805, respectively), and performed better than existing integrated models (P < 0.001 for all comparisons). In conclusion, high tumoral podoplanin expression could independently predict an adverse clinical outcome for ccRCC patients, and it might be useful in future for clinical decision-making and therapeutic developments. PMID- 27389971 TI - Agility in adversity: Vaccines on Demand. AB - Is the US ready for a biological attack using Ebola virus or Anthrax? Will vaccine developers be able to produce a Zika virus vaccine, before the epidemic spreads around the world? A recent report by The Blue Ribbon Study Panel on Biodefense argues that the US is not ready for these challenges, however, technologies and capabilities that could address these deficiencies are within reach. Vaccine technologies have advanced and readiness has improved in recent years, due to advances in sequencing technology and computational power making the 'vaccines on demand' concept a reality. Building a robust strategy to design effective biodefense vaccines from genome sequences harvested by real-time biosurveillance will benefit from technologies that are being brought to bear on the cancer cure 'moonshot'. When combined with flexible vaccine production platforms, vaccines on demand will relegate expensive and, in some cases, insufficiently effective vaccine stockpiles to the dust heap of history. PMID- 27389972 TI - Genetically Different Highly Pathogenic Avian Influenza A(H5N1) Viruses in West Africa, 2015. AB - To trace the evolution of highly pathogenic influenza A(H5N1) virus in West Africa, we sequenced genomes of 43 viruses collected during 2015 from poultry and wild birds in 5 countries. We found 2 co-circulating genetic groups within clade 2.3.2.1c. Mutations that may increase adaptation to mammals raise concern over possible risk for humans. PMID- 27389973 TI - Estimated pKa values for the environmentally relevant C1 through C8 perfluorinated sulfonic acid isomers. AB - In order to estimate isomer-specific acidity constants (pKa) for the perfluorinated sulfonic acid (PFSA) environmental contaminants, the parameterization method 6 (PM6) pKa prediction method was extensively validated against a wide range of carbon oxyacids and related sulfonic/sulfinic acids. Excellent pKa prediction performance was observed for the carbon oxyacids using the PM6 method, but this approach was found to have a severe positive bias for sulfonic/sulfinic acids. To overcome this obstacle, a correlation was developed between non-adjusted PM6 pKa values and the corresponding experimentally obtained/estimated acidity constants for a range of representative alkyl, aryl and halogen-substituted sulfonic acids. Application of this correction to the PM6 values allows for extension of this computational method to a new acid functional group. When used to estimate isomer-specific pKa values for the C1 through C8 PFSAs, the modified PM6 approach suggests an adjusted pKa range from -5.3 to 9.0, indicating that all members of this class of well-known environmental contaminants will be effectively completely dissociated in aquatic systems. PMID- 27389974 TI - Long-term outcome for patients with early stage marginal zone lymphoma and mantle cell lymphoma. AB - In this study with prolonged follow up, we compared clinical outcome, including cause of death and incidence of second cancer, for patients with early stage extranodal marginal zone lymphoma (EMZL, 49 patients), nodal marginal zone lymphoma (NMZL, nine patients) and mantle cell lymphoma (MCL, 42 patients) with emphasis on potential benefit of radiotherapy. Radiotherapy was given to 40 patients with EMZL (nine had surgery only) and all NMZL patients. MCL patients received radiotherapy (17 patients), chemotherapy followed by radiotherapy (13 patients) or chemotherapy alone (12 patients). Compared to a matched control population no increased risk of second cancer or cardiovascular disease was observed. Radiotherapy alone was effective in EMZL and NMZL with low-relapse rates (20% and 33%) and a 10-year overall survival of 78% and 56%, respectively. High-relapse rate and inferior OS in MCL underline the need for extended staging with endoscopy and PET/CT and possibly for novel strategies. PMID- 27389976 TI - The RBSS Patronage of local scientific surgical meetings. PMID- 27389977 TI - 11(th) Belgian Surgical Week. PMID- 27389975 TI - A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy. AB - OBJECTIVE: To compare the efficacy and safety of ABT-494, a novel selective JAK-1 inhibitor, with placebo in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response or intolerance to at least 1 anti-tumor necrosis factor (anti-TNF) agent. METHODS: In this 12-week, double-blind, placebo controlled, dose-ranging study, 276 RA patients receiving a stable dose of methotrexate (MTX) who had previously received treatment with at least 1 anti-TNF agent were randomized equally to receive immediate-release ABT-494 at 3, 6, 12, or 18 mg twice daily or matching placebo twice daily. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 12. RESULTS: At week 12, significantly more patients receiving ABT-494 (53-71%) than those receiving placebo (34%) achieved an ACR20 response (by nonresponder imputation analysis) (P < 0.05), with a dose-response relationship among all ABT-494 doses (P < 0.001). ACR50 and ACR70 response rates were significantly higher in those receiving ABT 494 (36-42% and 22-26%, respectively) than in those receiving placebo (16% and 4%, respectively). Changes from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) were significantly greater for all doses of ABT-494 than for placebo (P <= 0.01). Onset of action of ABT-494 was rapid, with significant differences from placebo at week 2 both in ACR20 response rate (for 12 and 18 mg) and in change in the DAS28-CRP (P < 0.001 for 6 18 mg). The most frequent adverse events (AEs) were headache, nausea, upper respiratory tract infection, and urinary tract infection. Infection rates were higher at higher doses of ABT-494, but no infections were serious. No deaths were reported among those receiving ABT-494. CONCLUSION: In patients with an inadequate response or intolerance to anti-TNF agents, ABT-494 added to MTX showed rapid, dose-dependent improvements in RA signs and symptoms, with safety and tolerability similar to those of other drugs of this class. No new AEs were identified. PMID- 27389979 TI - In Memoriam Andre Nevelsteen (1951-2009). PMID- 27389978 TI - The new RBSS Platform for Internet Based Scientific Studies. PMID- 27389980 TI - Development vs. behavior: a role for neural adaptation in evolution? AB - We examine the evolution of sensory organ patterning in the lateral line system of fish. Based on recent studies of how this system develops in zebrafish, and on comparative analyses between zebrafish and tuna, we argue that the evolution of lateral line patterns is mostly determined by variations in the underlying developmental processes, independent of any selective pressure. Yet the development of major developmental innovations is so directly linked to their exploitation that it is hard not to think of them as selected for, i.e., adaptive. We propose that adaptation resides mostly in how the nervous system adjusts to new morphologies to make them functional, i.e., that species are neurally adapted to whatever morphology is provided to them by their own developmental program. We show that recent data on behavioral differences between cave forms (blind) and surface forms (eyed) of the mexican fish Astyanax fasciatus support this view, and we propose that this species might provide a unique opportunity to assess the nature of adaptation and of selection in animal evolution. PMID- 27389981 TI - Hypoxia promotes thyroid differentiation of native murine induced pluripotent stem cells. AB - Hypothyroidism is a very common hormonal deficiency and the stem cell technology which developed in the recent years may offer a therapeutic strategy for treating this disorder. Hypoxia has been demonstrated to play an important role in embryonic formation and development and to modulate stem cell differentiation. However, the influence of oxygen tension on thyroid differentiation has not been studied. In this study, we used murine induced pluripotent stem (iPS) cells for thyroid cell differentiation under normoxic and hypoxic conditions and compared differentiation efficiency in morphology, function, gene and protein expression under both conditions. We found that hypoxia promoted adhesion and outgrowth of embryoid bodies (EBs) derived from murine iPS cells. Expression of endodermal markers (Foxa2 and Gata4) and thyroid transcription factors (Pax8 and Nkx2.1) was increased by hypoxia at both gene and protein levels during early-mid differentiation stages (p<0.05). And so were the thyroid specific markers NIS and TSHR at the end of the experiment (p<0.05). In addition, functional iodide uptake by differentiated cells was also increased after hypoxia. Thyroid differentiation from iPS cells is enhanced under hypoxia and this may involve hypoxia inducible factors (HIFs) and their downstream gene FGF2. Our data offer a foundation for understanding thyroid development and provide a potentially more efficient way to use cell therapy for treating thyroid deficiency. PMID- 27389982 TI - The effect of amniotic membrane stem cells as donor nucleus on gene expression in reconstructed bovine oocytes. AB - Nuclear reprogramming of a differentiated cell in somatic cell nuclear transfer (SCNT) is a major concern in cloning procedures. Indeed, the nucleus of the donor cell often fails to express the genes which are a prerequisite for normal early embryo development. This study was aimed to evaluate the developmental competence and the expression pattern of some reprogramming related genes in bovine cloned embryos reconstructed with amniotic membrane stem cells (AMSCs) in comparison with those reconstructed with mesenchymal stem cells (MSCs) and adult fibroblasts (AF) as well as with in vitro fertilized (IVF) oocytes. In vitro matured abattoir derived oocytes were considered as recipients and a hand-made cloning technique was employed for oocyte enucleation and nuclear transfer (NT) procedures. The expression pattern of genes involved in self-renewal and pluripotency (POU5F1, SOX2, NANOG), imprinting (IGF2, IGF2R), DNA methylation (DNMT1, DNMT3A), histone deacetylation (HDAC2), and apoptosis (BAX, BCL2) were evaluated in NT and IVF derived embryos. Despite the insignificant difference in cleavage rate between reconstructed and IVF oocytes, the blastocyst rate in the IVF group was higher than that of other groups. Among reconstructed oocytes, a higher blastocysts rate was observed in MSC-NT and AMSCs-NT derived embryos that were significantly higher than AF-NT derived ones. There were more similarities in the expression pattern of pluripotency and epigenetic modification genes between MSC-NT and IVF derived blastocysts compared with other groups. In conclusion, considering developmental competence, AMSCs, as alternative donors in SCNT procedure, like MSCs, were prone to have more advantage compared with AF. PMID- 27389983 TI - Comparative epigenetic evaluation of human embryonic stem and induced pluripotent cells. AB - Histone H3 lysine 9 methylation has been shown to be a critical barrier to efficient cell reprogramming. This discovery allows the assessment of the cell pluripotency state by considering the extent of H3K9 methylation vs. acetylation at the same position. A set of pluripotent and differentiated human cells including embryonic stem cells, their differentiated and reprogrammed counterparts, along with human fibroblasts and their derived reprogrammed cells, were used to evaluate the ratio of total H3K9 methylation over acetylation using a quantitative ELISA-based approach. Also, the occurrence of the H3K4me3 and H3K27me3 bivalent marks was evaluated. Additionally, using ChIP-qPCR the occurrence of these histone marks on the regulatory regions of stemness genes (Nanog, Oct4 and Sox2) as well as on genes indicating fibroblast differentiation (Vim, COL1A1 and THY1) was evaluated. We evidence remarkably high ratios of H3K9ac/K9me2 in ES and iPS cells vs. differentiated cells. In iPSCs, a direct relationship between the ratios of total H3K9ac/H3K9me2 and the ratios of these marks on pluripotency gene regulatory regions and their expression was observed. In differentiated cells, in contrast, the ratios of global H3K9ac/K9me2 is low but the active genes escape this general situation and bear higher amounts of H3K9ac vs. H3K9me. Total H3K4me3/K27me3 ratios presented the same trends, but with reduced amplitudes. We propose that the rapid quantitative measurements of relative amounts of H3K9ac and K9me2 in iPS cells compared to the parental differentiated cells constitute a reliable and convenient criterion to rapidly assess the cell pluripotency potentials and the efficiency of cell reprogramming. PMID- 27389984 TI - Genome-wide identification of enhancer elements. AB - We present a prospective genome-wide regulatory element database for the sea urchin embryo and the modified chromosome capture-related methodology used to create it. The method we developed is termed GRIP-seq for genome-wide regulatory element immunoprecipitation and combines features of chromosome conformation capture, chromatin immunoprecipitation, and paired-end next-generation sequencing with molecular steps that enrich for active cis-regulatory elements associated with basal transcriptional machinery. The first GRIP-seq database, available to the community, comes from S. purpuratus 24 hpf embryos and takes advantage of the extremely well-characterized cis-regulatory elements in this system for validation. In addition, using the GRIP-seq database, we identify and experimentally validate a novel, intronic cis-regulatory element at the onecut locus. We find GRIP-seq signal sensitively identifies active cis-regulatory elements with a high signal-to-noise ratio for both distal and intronic elements. This promising GRIP-seq protocol has the potential to address a rate-limiting step in resolving comprehensive, predictive network models in all systems. PMID- 27389985 TI - Noggin 1 overexpression in retinal progenitors affects bipolar cell generation. AB - Waves of Bone Morphogenetic Proteins (BMPs) and their antagonists are present during initial eye development, but their possible roles in retinogenesis are still unknown. We have recently shown that noggin 1, a BMP antagonist, renders pluripotent cells able to differentiate into retinal precursors, and might be involved in the maintenance of retinal structures in the adult vertebrate eye. Here, we report that noggin 1, differently from noggin 2 and noggin 4, is expressed during all phases of Xenopus laevis retinal development. Gain-of function experiments by electroporation in the optic vesicle show that overexpression of noggin 1 significantly decreases the number of bipolar cells in the inner nuclear layer of the retina, without significantly affecting the generation of the other retinal cell types. Our data suggest that BMP signaling could be involved in the differentiation of retinal progenitors into specific retinal subtypes during late phases of vertebrate retinal development. PMID- 27389987 TI - Platelet derived growth factor B gene expression in the Xenopus laevis developing central nervous system. AB - Platelet-derived growth factor B (PDGF-B) belongs to the mitogen and growth factor family and like the other members it has many roles in cell differentiation, proliferation and migration during development, adult life and in pathological conditions. Among them it has been observed that aberrant PDGF signalling is frequently linked to glioma development and progression, and Pdgf-b over-expression in mouse neural progenitors leads to the formation of gliomas. Despite this evidence, the mechanisms underlying PDGF-B driven tumorigenesis and its role during brain development are not fully understood. In order to contribute to clarifying possible new roles of pdgf-b signalling, we present here the embryonic gene expression pattern of pdgf-b, so far unknown in early vertebrate development. By using Xenopus laevis as a model system we performed qRT-PCR and whole mount in situ hybridization. Pdgf-b mRNA is expressed in discrete regions of the developing central nervous system, in the cranial nerve placodes and in the notochord. We also compared the gene expression of pdgf-b with that of its receptor pdgfr-alpha suggesting so far unsuspected roles for this signalling pathway during the development of specific embryonic structures. PMID- 27389986 TI - Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest. AB - Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2. In order to advance understanding of the function of Kctd15 during NC development, we performed DNA microarray assays in explants injected with Wnt3a and Chordin, and identified genes that are affected by Kctd15 overexpression. Among the many genes identified, we chose Duf domain containing protein 1 (ddcp1), Platelet-Derived Growth Factor Receptor a (pdgfra), Complement factor properdin (cfp), Zinc Finger SWIM-Type Containing 5 (zswim5), and complement component 3 (C3) to examine their expression by whole mount in situ hybridization. Our work points to a possible role for Kctd15 in the regulation of NC formation and other steps in embryonic development. PMID- 27389988 TI - Nucleoporin gene expression in Xenopus tropicalis embryonic development. AB - Nucleoporins (nups) compose the structure of the nuclear pore complex (NPC) of all cells, but several studies have illuminated nucleoporins' additional roles in development and the cell cycle. However, a comprehensive study of nup expression in embryonic development has not yet been reported. We synthesized antisense probes for all nup genes and used whole-mount in situ hybridization techniques to determine the expression pattern of all members of the nup family of genes at three different developmental stages in Xenopus tropicalis. We found that the expression of nups was not ubiquitous in embryos, but was localized to specific and distinguishable anatomical structures at all three stages tested. We also found that the expression patterns for nups within the same subcomplexes were not necessarily identical. Thus, nup expression is subject to a significant level of regulation during development. These results provide new information for functional studies of nups to unravel their roles in embryonic development. PMID- 27389989 TI - Real-Time Dynamics of Galvanic Replacement Reactions of Silver Nanocubes and Au Studied by Liquid-Cell Transmission Electron Microscopy. AB - We study the galvanic replacement reaction of silver nanocubes in dilute, aqueous ethylenediaminetetraacetic acid disodium salt (EDTA)-capped gold aurate solutions using in situ liquid-cell electron microscopy. Au/Ag etched nanostructures with concave faces are formed via (1) etching that starts from the faces of the nanocubes, followed by (2) the deposition of an Au layer as a result of galvanic replacement, and (3) Au deposition via particle coalescence and monomer attachment where small nanoparticles are formed during the reaction as a result of radiolysis. Analysis of the Ag removal rate and Au deposition rate provides a quantitative picture of the growth process and shows that the morphology and composition of the final product are dependent on the stoichiometric ratio between Au and Ag. PMID- 27389990 TI - Assuring blood safety and availability: Zika virus, the latest emerging infectious disease battlefront. PMID- 27389991 TI - The trials and tribulations of chronic transfusion in pediatric sickle cell disease: progress from STOP to TWiTCH? PMID- 27389992 TI - Bench to bedside: the challenge and promise of translating basic research discoveries in thrombotic microangiopathies. PMID- 27389993 TI - A case of cryocrystalglobulinemia. PMID- 27389995 TI - Erratum. PMID- 27389996 TI - Research trends and perspectives of male infertility: a bibliometric analysis of 20 years of scientific literature. AB - To carry out an in-depth analysis of the scientific research on male infertility, we performed the first bibliometric analysis focusing on studies involving male infertility worldwide during the period 1995-2014. Analysis of 6357 articles in the field of male infertility showed a significant increasing trend in the number of publications over the period 1995-2014. Obstetrics and Gynecology was an important subject category and Multidisciplinary Sciences was the newest interest. Authors were mainly from Europe and USA, with researchers from Cleveland Clinic producing the most articles, and those from the Tel Aviv Sourasky Medical Center and the University of Utah having the highest-quality articles. The USA contributed the most independent and international collaborative articles. The Cleveland Clinic and the University of Munster were the most productive institutions. The Cleveland Clinic and the University of Giessen had the most international collaboration publications. Harvard University had the most collaborators. The most common interests were pathogenesis and therapy, and new interests were hypogonadism, obesity, and cryopreservation. In conclusion, rapid development of the male infertility field was observed. Overall, collaborative and multidisciplinary science research has become more popular. The USA and its institutions play a dominant role, followed by European countries. Thanks to the common research focus worldwide, more insight into male fertility has been gained in the scientific literature over the past 20 years. [Correction added on September 21, 2016, after online publication: the term "institute" has been replaced by the term "institution" throughout the text.]. PMID- 27389997 TI - Influence of fossil-fuel power plant emissions on the surface fine particulate matter in the Seoul Capital Area, South Korea. AB - The South Korean government plans to reduce region-wide annual PM2.5 (particulate matter with an aerodynamic diameter <=2.5 MUm) concentrations in the Seoul Capital Area (SCA) from 2010 levels of 27 ug/m(3) to 20 ug/m(3) by 2024. At the same time, it is inevitable that emissions from fossil-fuel power plants will continue to increase if electricity generation expands and the generation portfolio remains the same in the future. To estimate incremental PM2.5 contributions due to projected electricity generation growth in South Korea, we utilized an ensemble forecasting member of the Integrated Multidimensional Air Quality System for Korea based on the Community Multi-scale Air Quality model. We performed sensitivity runs with across-the-board emission reductions for all fossil-fuel power plants in South Korea to estimate the contribution of PM2.5 from domestic fossil-fuel power plants. We estimated that fossil-fuel power plants are responsible for 2.4% of the annual PM2.5 national ambient air quality standard in the SCA as of 2010. Based on the electricity generation and the annual contribution of fossil-fuel power plants in 2010, we estimated that annual PM2.5 concentrations may increase by 0.2 ug/m(3) per 100 TWhr due to additional electricity generation. With currently available information on future electricity demands, we estimated that the total future contribution of fossil fuel power plants would be 0.87 ug/m(3), which is 12.4% of the target reduction amount of the annual PM2.5 concentration by 2024. We also approximated that the number of premature deaths caused by existing fossil-fuel power plants would be 736 in 2024. Since the proximity of power plants to the SCA and the types of fuel used significantly impact this estimation, further studies are warranted on the impact of physical parameters of plants, such as location and stack height, on PM2.5 concentrations in the SCA due to each precursor. IMPLICATIONS: Improving air quality by reducing fine particle pollution is challenging when fossil-fuel based electricity production is increasing. We show that an air quality forecasting system based on a photochemical model can be utilized to efficiently estimate PM2.5 contributions from and health impacts of domestic power plants. We derived PM2.5 concentrations per unit amount of electricity production from existing fossil-fuel power plants in South Korea. We assessed the health impacts of existing fossil-fuel power plants and the PM2.5 concentrations per unit electricity production to quantify the significance of existing and future fossil fuel power plants with respect to the planned PM2.5 reduction target. PMID- 27389998 TI - Clinical Risk Factors for the Presence and Development of Vertebral Fractures in Patients With Ankylosing Spondylitis. AB - INTRODUCTION: To investigate the prevalence and incidence of radiographic vertebral fractures and the association with patient characteristics, clinical assessments, and medication use in a large prospective cohort of patients with ankylosing spondylitis (AS) in daily clinical practice. METHODS: Consecutive AS patients from the Groningen Leeuwarden AS (GLAS) cohort with baseline and 2-year lateral radiographs of the thoracic and lumbar spine were included. Radiographs were scored for vertebral fractures by 2 readers according to the method of Genant et al. Differences in baseline characteristics between patients with and without radiographic vertebral fractures were explored. RESULTS: Of 292 included AS patients, 59 (20%) had radiographic vertebral fractures at baseline, 15 (6%) developed new fractures, and 7 (2%) showed an increase in the severity of existing fractures during 2 years of follow-up. Most fractures were mild and located in the midthoracic and thoracolumbar region of the spine. The presence of vertebral fractures was significantly associated with older age, higher body mass index, longer smoking duration, larger occiput-to-wall distance, more spinal radiographic damage, and lower hip bone mineral density (BMD). The development of new or progressive vertebral fractures was also associated with older age and low BMD. Patients using nonsteroidal antiinflammatory drugs (NSAIDs) at baseline showed less prevalent and incident vertebral fractures. CONCLUSION: In this large AS cohort in daily clinical practice, radiographic vertebral fractures were frequently present in AS, especially in older patients with more advanced disease, low hip BMD, and a less healthy lifestyle. Interestingly, NSAID use was associated with a reduced vertebral fractures risk. PMID- 27389999 TI - Reasons for Infant Feeding Decisions in Low-Income Families in Washington, DC. AB - BACKGROUND: Breastfeeding rates for low-income, African American infants remain low. OBJECTIVE: This study aimed to determine the barriers, support, and influences for infant feeding decisions among women enrolled in the Washington, DC, Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) after revisions in the WIC package to include more food vouchers for breastfeeding mothers and their infants and improvement of in-hospital breastfeeding support. METHODS: We surveyed 100 women, using a 42-item verbally administered survey that asked about demographics, infant feeding method, and influences and support for feeding decisions. RESULTS: The majority of participants (76%) initiated breastfeeding; 31% exclusively breastfed in the hospital. Participants were more likely to breastfeed if they had some college education, were unemployed or employed full-time, had only one child, and had been breastfed themselves as infants. Barriers to prolonged breastfeeding included limited support after hospital discharge, pain, and perceived insufficient milk supply. Participants in this study had higher breastfeeding initiation and in-hospital exclusivity rates after improvement of in-hospital breastfeeding support. CONCLUSION: Clients of WIC initiated breastfeeding at a high rate but either supplemented with formula or stopped breastfeeding for reasons that could be remedied by improved prenatal education, encouragement of exclusive breastfeeding in the hospital, and more outpatient support. PMID- 27390000 TI - Editorial. PMID- 27390001 TI - Genetic characterisation of H9N2 influenza viruses in southern China. PMID- 27390002 TI - Susceptibility of the upper respiratory tract to influenza virus infection following desialylation. PMID- 27390003 TI - Definition of the cellular interactome of the highly pathogenic avian influenza H5N1 virus: identification of human cellular regulators of viral entry, assembly, and egress. PMID- 27390004 TI - A bioshield against influenza virus infection by commensal bacteria secreting antiviral peptide. PMID- 27390005 TI - Oral feeding of minocycline attenuates glial activation and reductions of tau and drebrin in response to systemically injected cytokines. PMID- 27390006 TI - Modulation of cell signalling by human coronavirus HKU1 S and M proteins. PMID- 27390007 TI - Antibody-dependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS. PMID- 27390008 TI - Structure-based discovery and development of natural products as Type II JAK2 inhibitors for the treatment of hepatitis C. PMID- 27390009 TI - Functional characterisation of hepatitis B viral X protein/microRNA-21 interaction in HBV-associated hepatocellular carcinoma. PMID- 27390010 TI - Gender disparity of hepatocellular carcinoma: role of hepatitis B virus X protein and androgen receptor. PMID- 27390012 TI - Diabetes remission off medications is not a suitable endpoint for comparing bariatric/metabolic surgery with pharmacotherapy. Reply to Halpern B, Cercato C, Mancini MC [letter]. PMID- 27390011 TI - Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. AB - AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells. METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism. PMID- 27390013 TI - Clinical feasibility of dried blood spots: Analytics, validation, and applications. AB - Dried blood spots (DBS) sampling and their specific advantages are becoming common in analytical and clinical routine. Being first established for metabolic disorder screening in neonates, its use emerged to a broad spectrum of clinical applications. Although DBS are easily generated, the conduction of specific analytical and clinical validation procedures should be obligatory when implementing DBS for clinical purposes, e.g. therapeutic drug monitoring or clinical drug trials. A respective recommendation has already been published by the European Bioanalysis Forum. Since no official guidelines are present, investigators are currently free in DBS procedure development and validation. This review summarizes and discusses published clinical validation procedures in relation to their applications to highlight the clinical feasibility of DBS. PMID- 27390015 TI - A novel Si/Sn composite with entangled ribbon structure as anode materials for lithium ion battery. AB - A novel Si/Sn composite anode material with unique ribbon structure was synthesized by Mechanical Milling (MM) and the structural transformation was studied in the present work. The microstructure characterization shows that Si/Sn composite with idealized entangled ribbon structured can be obtained by milling the mixture of the starting materials, Si and Sn for 20 h. According to the calculated results based on the XRD data, the as-milled 20 h sample has the smallest avergae crystalline size. It is supposed that the flexible ribbon structure allows for accommodation of intrinsic damage, which significantly improves the fracture toughness of the composite. The charge and discharge tests of the as-milled 20 h sample have been performed with reference to Li(+)/Li at a current density of 400 mA g(-1) in the voltage from 1.5 to 0.03 V (vs Li/Li(+)) and the result shows that the initial capacity is ~1400 mA h g(-1), with a retention of ~1100 mA h g(-1) reversible capacity after 50 cycles, which is possible serving as the promising anode material for the lithium ion battery application. PMID- 27390014 TI - Polarity control in WSe2 double-gate transistors. AB - As scaling of conventional silicon-based electronics is reaching its ultimate limit, considerable effort has been devoted to find new materials and new device concepts that could ultimately outperform standard silicon transistors. In this perspective two-dimensional transition metal dichalcogenides, such as MoS2 and WSe2, have recently attracted considerable interest thanks to their electrical properties. Here, we report the first experimental demonstration of a doping free, polarity-controllable device fabricated on few-layer WSe2. We show how modulation of the Schottky barriers at drain and source by a separate gate, named program gate, can enable the selection of the carriers injected in the channel, and achieved controllable polarity behaviour with ON/OFF current ratios >10(6) for both electrons and holes conduction. Polarity-controlled WSe2 transistors enable the design of compact logic gates, leading to higher computational densities in 2D-flatronics. PMID- 27390016 TI - 12(S)-HETE increases intracellular Ca(2+) in lymph-endothelial cells disrupting their barrier function in vitro; stabilization by clinical drugs impairing calcium supply. AB - Secretion of 12(S)-HETE by breast cancer emboli provokes "circular chemorepellent induced defects" (CCIDs) in the adjacent lymphatic vasculature facilitating their intravasation and lymph node metastasis which determines prognosis. Therefore, elucidating the mechanism of lymph endothelial cell (LEC) wall disintegration may provide cues for anti-metastatic intervention. The role of intracellular free Ca(2+) for CCID formation was investigated in LECs using MCF-7 or MDA-MB231 breast cancer cell spheroids in a three-dimensional cell co-culture model. 12(S) HETE elevated the Ca(2+) level in LEC by activating PLC/IP3. Downstream, the Ca(2+)-calmodulin kinase MYLK contributed to the phosphorylation of Ser19-MLC2, LEC contraction and CCID formation. Approved clinical drugs, lidoflazine, ketotifen, epiandrosterone and cyclosporine, which reportedly disturb cellular calcium supply, inhibited 12(S)-HETE-induced Ca(2+) increase, Ser19-MLC2 phosphorylation and CCID formation. This treatment strategy may reduce spreading of breast cancer through lymphatics. PMID- 27390018 TI - Infection Prevention and Control for Ebola in Health Care Settings - West Africa and United States. AB - The 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa underscores the need for health care infection prevention and control (IPC) practices to be implemented properly and consistently to interrupt transmission of pathogens in health care settings to patients and health care workers. Training and assessing IPC practices in general health care facilities not designated as Ebola treatment units or centers became a priority for CDC as the number of Ebola virus transmissions among health care workers in West Africa began to affect the West African health care system and increasingly more persons became infected. CDC and partners developed policies, procedures, and training materials tailored to the affected countries. Safety training courses were also provided to U.S. health care workers intending to work with Ebola patients in West Africa. As the Ebola epidemic continued in West Africa, the possibility that patients with Ebola could be identified and treated in the United States became more realistic. In response, CDC, other federal components (e.g., Office of the Assistant Secretary for Preparedness and Response) and public health partners focused on health care worker training and preparedness for U.S. health care facilities. CDC used the input from these partners to develop guidelines on IPC for hospitalized patients with known or suspected Ebola, which was updated based on feedback from partners who provided care for Ebola patients in the United States. Strengthening and sustaining IPC helps health care systems be better prepared to prevent and respond to current and future infectious disease threats.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014 west-africa/partners.html). PMID- 27390019 TI - Peripheral Interventions Enhancing Brain Glutamate Homeostasis Relieve Amyloid beta- and TNFalpha- Mediated Synaptic Plasticity Disruption in the Rat Hippocampus. AB - Dysregulation of glutamate homeostasis in the interstitial fluid of the brain is strongly implicated in causing synaptic dysfunction in many neurological and psychiatric illnesses. In the case of Alzheimer's disease (AD), amyloid beta (Abeta)-mediated disruption of synaptic plasticity and memory can be alleviated by interventions that directly remove glutamate or block certain glutamate receptors. An alternative strategy is to facilitate the removal of excess glutamate from the nervous system by activating peripheral glutamate clearance systems. One such blood-based system, glutamate oxaloacetate transaminase (GOT), is activated by oxaloacetate, which acts as a co-substrate. We report here that synthetic and AD brain-derived Abeta-mediated inhibition of synaptic long-term potentiation in the hippocampus is alleviated by oxaloacetate. Moreover the effect of oxaloacetate was GOT-dependent. The disruptive effects of a general inhibitor of excitatory amino acid transport or TNFalpha, a pro-inflammatory mediator of Abeta action, were also reversed by oxaloacetate. Furthermore, another intervention that increases peripheral glutamate clearance, peritoneal dialysis, mimicked the beneficial effect of oxaloacetate. These findings lend support to the promotion of the peripheral clearance of glutamate as a means to alleviate synaptic dysfunction that is caused by impaired glutamate homeostasis in the brain. PMID- 27390021 TI - Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. AB - : By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol <=50nmol/L (1.8ug/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5ug/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas. PMID- 27390020 TI - Correlations Between Personality and Brain Structure: A Crucial Role of Gender. AB - Previous studies have shown that males and females differ in personality and gender differences have also been reported in brain structure. However, effects of gender on this "personality-brain" relationship are yet unknown. We therefore investigated if the neural correlates of personality differ between males and females. Whole brain voxel-based morphometry was used to investigate the influence of gender on associations between NEO FFI personality traits and gray matter volume (GMV) in a matched sample of 182 males and 182 females. In order to assess associations independent of and dependent on gender, personality-GMV relationships were tested across the entire sample and separately for males and females. There were no significant correlations between any personality scale and GMV in the analyses across the entire sample. In contrast, significant associations with GMV were detected for neuroticism, extraversion, and conscientiousness only in males. Interestingly, GMV in left precuneus/parieto occipital sulcus correlated with all 3 traits. Thus, our results indicate that brain structure-personality relationships are highly dependent on gender, which might be attributable to hormonal interplays or differences in brain organization between males and females. Our results thus provide possible neural substrates of personality-behavior relationships and underline the important role of gender in these associations. PMID- 27390023 TI - Association Between Body Mass Index and Diabetes in Northeastern China: Based on Dose-Response Analyses Using Restricted Cubic Spline Functions. AB - A high body mass index (BMI) is a major risk factor for diabetes, although little is known about the characterization of a dose-response association adjusted for potential confounders. This cross-sectional study was conducted from June 2012 to August 2012; a total of 21 435 inhabitants in Jilin Province aged between 18 and 79 years were selected randomly based on multistage, stratified cluster sampling. The estimated prevalence of diabetes was 9.1% overall, 9.4% in males and 8.9% in females. After adjusting for potential confounders, the multivariable-adjusted odds ratios for the BMI-diabetes association were 1.337 (95% confidence interval = 1.185-1.508) and 1.696 (95% confidence interval = 1.429-2.042), respectively, for overweight and obesity. Through multivariable restricted cubic spline regression, continuous variation in BMI was found to be related to diabetes in a nonlinear manner (P < .001) after adjustment for confounders in both different gender and different age groups, suggesting that there is an adjusted dose response association between continuous BMI and diabetes, with substantial population-level effects. PMID- 27390024 TI - A Comparison of Spatial Pattern Detection Methods for Major Cancer Mortality in Korea. AB - Spatial pattern detection can be a useful tool for understanding the geographical distribution of cancer mortality. This study compared the results from several special analysis methods to examine the geographical variations in Korean major cancer mortality during 2010 to 2013. The spatial scan statistic and Tango's method were used to detect spatial clusters with unusually high or low rates. The local indicator of spatial association was used for cluster detection with accounting for spatial autocorrelation among adjacent areas. A nonparametric approach was used to identify local districts with significantly higher or lower rates, compared to the average national rate. The different methods revealed similar results in the overall patterns, but slightly different specific results. These techniques can provide complementary information and should be used based on the distinguishing features of each method. It may be better to use several different methods for these analyses rather than a single method. PMID- 27390022 TI - Srs2 and Mus81-Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates. AB - Homologous recombination is an evolutionally conserved mechanism that promotes genome stability through the faithful repair of double-strand breaks and single strand gaps in DNA, and the recovery of stalled or collapsed replication forks. Saccharomyces cerevisiae ATP-dependent DNA helicase Srs2 (a member of the highly conserved UvrD family of helicases) has multiple roles in regulating homologous recombination. A mutation (srs2K41A) resulting in a helicase-dead mutant of Srs2 was found to be lethal in diploid, but not in haploid, cells. In diploid cells, Srs2K41A caused the accumulation of inter-homolog joint molecule intermediates, increased the levels of spontaneous Rad52 foci, and induced gross chromosomal rearrangements. Srs2K41A lethality and accumulation of joint molecules were suppressed by inactivating Rad51 or deleting the Rad51-interaction domain of Srs2, whereas phosphorylation and sumoylation of Srs2 and its interaction with sumoylated proliferating cell nuclear antigen (PCNA) were not required for lethality. The structure-specific complex of crossover junction endonucleases Mus81 and Mms4 was also required for viability of diploid, but not haploid, SRS2 deletion mutants (srs2Delta), and diploid srs2Delta mus81Delta mutants accumulated joint molecule intermediates. Our data suggest that Srs2 and Mus81 Mms4 have critical roles in preventing the formation of (or in resolving) toxic inter-homolog joint molecules, which could otherwise interfere with chromosome segregation and lead to genetic instability. PMID- 27390026 TI - The relationship between the theory of planned behavior and medication adherence in patients with epilepsy. AB - PURPOSE: The aim of this study was to apply the theory of planned behavior (TPB) with two other factors (action planning and coping planning) to the medication adherence of adults with epilepsy. METHODS: We measured the elements of the theory of planned behavior (attitude, subjective norm, perceived behavioral control, and behavioral intention), action planning, and coping planning at baseline among adults with epilepsy (n=567, mean+/-SD age=38.37+/-6.71years, male=48.5%). Medication adherence was measured using the Medication Adherence Report Scale (MARS) and antiepileptic serum level at the 24-month follow-up. Structural equation modeling (SEM) examined three models relating TPB elements to medication adherence. RESULTS: Three SEM models all had satisfactory fit indices. Moreover, attitude, subjective norms, perceived behavioral control, and intention together explained more than 50% of the variance for medication adherence measured using MARS. The explained variance increased to 61.8% when coping planning and action planning were included in the model, with coping planning having greater association than action planning. In addition, MARS explained 3 to 5% of the objective serum level. CONCLUSION: The theory of planned behavior is useful in understanding medication adherence in adults with epilepsy, and future interventions may benefit by improving such beliefs as well as beliefs about coping planning. PMID- 27390025 TI - A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling. AB - SCOPE: Activation of the nod-like receptor protein 3 (NLRP3) inflammasome is required for IL-1beta release and is a key component of obesity-induced inflammation and insulin resistance. This study hypothesized that supplementation with a casein hydrolysate (CH) would attenuate NLRP3 inflammasome mediated IL 1beta secretion in adipose tissue (AT) and improve obesity-induced insulin resistance. METHODS AND RESULTS: J774.2 macrophages were LPS primed (10 ng/mL) and stimulated with adenosine triphosphate (5 mM) to assess NLRP3 inflammasome activity. Pretreatment with CH (1 mg/mL; 48 h) reduced caspase-1 activity and decreased IL-1beta secretion from J774.2 macrophages in vitro. 3T3-L1 adipocytes cultured with conditioned media from CH-pretreated J774.2 macrophages demonstrated increased phosphorylated (p)AKT expression and improved insulin sensitivity. C57BL/6JOLaHsd mice were fed chow or high fat diet (HFD) for 12 wk +/- CH resuspended in water (0.5% w/v). CH supplementation improved glucose tolerance in HFD-fed mice as determined by glucose tolerance test. CH supplementation increased insulin-stimulated pAKT protein levels in AT, liver, and muscle after HFD. Cytokine secretion was measured from AT and isolated bone marrow macrophages cultured ex vivo. CH supplementation attenuated IL-1beta, tumor necrosis factor alpha (TNF-alpha) and IL-6 secretion from AT and IL-1beta, IL-18, and TNF-alpha from bone marrow macrophages following adenosine triphosphate stimulation ex vivo. CONCLUSION: This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1beta secretion and improved insulin signaling. PMID- 27390027 TI - Measurement of Change in Lower Eyelid Position in Patients Undergoing Transcutaneous Skin-Muscle Flap Lower Eyelid Blepharoplasty. AB - Importance: Transcutaneous lower eyelid blepharoplasty is a commonly performed procedure with a postoperative risk of eyelid malposition. Objective: To quantify the change in lower eyelid position after transcutaneous lower eyelid blepharoplasty. Design, Setting, and Participants: This retrospective medical record review describes patients who underwent transcutaneous blepharoplasty at a private facial plastic surgery practice. Patients with less than 3 months of follow-up, a history of periocular trauma, and concurrent midface lift were excluded. Interventions: Bilateral skin-muscle flap lower eyelid blepharoplasties with possible tarsorrhaphy, canthopexy, or canthoplasty as indicated. Main Outcomes and Measures: Lower eyelid position determined by measurement of preoperative and postoperative pupil to eyelid and lateral limbus to eyelid distances. Results: Data from 100 consecutive patients (mean age, 56.7 years; 92 female [92.0%]) undergoing bilateral skin-muscle flap lower eyelid blepharoplasty were analyzed. The mean increase in distance was 0.33 mm (95% CI, 0.24-0.42 mm) from the pupil to the lower eyelid margin and 0.32 mm (95% CI, 0.23-0.41 mm) from the lateral limbus to the lower eyelid margin at final follow-up. For both measurements, patients undergoing concurrent canthopexy had a significantly greater change in eyelid position (P < .001). Men had a greater change in the distance of pupil to lower eyelid compared with women (0.76 mm; 95% CI, 0.44-1.08 mm, vs 0.30 mm; 95% CI, 0.20-0.39 mm, respectively; P = .008) at final follow-up. Two patients required revision procedures secondary to eyelid malposition, and 25 patients had new onset of dry eye symptoms. Conclusions and Relevance: Transcutaneous skin-muscle lower eyelid blepharoplasty with selective performance of canthoplasty or canthopexy causes a small, predictable eyelid position change in this population with a low rate of revision procedures. Level of Evidence: 3. PMID- 27390028 TI - Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. AB - OBJECTIVE: Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. METHODS: In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 MUg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. RESULTS: Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. CONCLUSION: This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy. PMID- 27390029 TI - Diabetes-accelerated experimental osteoarthritis is prevented by autophagy activation. AB - OBJECTIVE: Type 2 Diabetes (T2D) is a risk factor for osteoarthritis (OA). Autophagy, an essential homeostasis mechanism in articular cartilage, is defective in T2D and OA. However, how T2D may influence OA progression is still unknown. We aimed to determine how diabetes affects cartilage integrity and whether pharmacological activation of autophagy has efficacy in diabetic mice (db/db mice) with OA. DESIGN: Experimental OA was performed in the right knee of 9 weeks-old C57Bl/6J male mice (Lean group, N = 8) and of 9 weeks-old B6.BKS (D) Leprdb male mice (db/db group, N = 16) by transection of medial meniscotibial and medial collateral ligaments. Left knee was employed as control knee. Rapamycin (2 mg/kg weight/day) or Vehicle (dimethyl sulfoxide) were administered intraperitoneally three times a week for 10 weeks. Histopathology of articular cartilage and synovium was evaluated by using semiquantitative scoring and synovitis grading systems, respectively. Immunohistochemistry was employed to evaluate the effect of diabetes and Rapamycin on cartilage integrity and OA biomarkers. RESULTS: Cartilage damage was increased in db/db mice compared to Lean mice after experimental OA, while no differences are observed in the control knee. Cartilage damage and synovium inflammation were reduced by Rapamycin treatment of OA-db/db mice. This protection was accompanied with a decrease in MMP-13 expression and decreased interleukin 12 (IL-12) levels. Furthermore, autophagy was increased and cartilage cellularity was maintained, suggesting that mammalian target of rapamycin (mTOR) targeting prevents joint physical harm. CONCLUSION: Our findings indicate that diabetic mice exhibit increased joint damage after experimental OA, and that autophagy activation might be an effective therapy for diabetes-accelerated OA. PMID- 27390030 TI - Articular cartilage calcification of the hip and knee is highly prevalent, independent of age but associated with histological osteoarthritis: evidence for a systemic disorder. AB - OBJECTIVES: Based on the concept of a systemic predisposition for articular cartilage calcification (CC), the aim of this study was to determine the prevalence and amount of bilateral CC of hip and knee joints in an unselected sample cohort by high-resolution digital contact radiography (DCR) and to analyze the association of CC with histological OA. METHODS: Both hip and knee joints of 87 donors (48 m and 39 f; mean age 62) were analyzed by DCR in this post-mortem study of an unselected cohort of donors. Histological OA (OARSI) of the main load bearing area of femoral heads and medial femoral condyles was determined. RESULTS: The prevalence of CC of the femoral head was 96.6%, of the knee 94.3%. Bilateral calcification was detected in 79.3% of hips and 86.2% of knees. Concomitant CC of all four joints was detected in 69.0% of donors. There was no difference between the amount of CC of hips and knees (P = 0.47). The amount of CC of any given hip or knee correlated with that of the contralateral hip (rs = 0.54, P < 0.001) or knee (rs = 0.50, P < 0.001). There was a correlation between the amount of CC and histological OA (hips rs = 0.48, P < 0.001, knees rs = 0.30, P = 0.004), but not between CC and age (hips rs = -0.09, P = 0.42; knees rs = 0.10, P = 0.34). CONCLUSIONS: These data support the concept that articular CC occurs as the result of a systemic disorder. CC appears to be an early element of hip and knee OA pathogenesis independent of age. PMID- 27390031 TI - The incident tibiofemoral osteoarthritis with rapid progression phenotype: development and validation of a prognostic prediction rule. AB - OBJECTIVES: No clinical prediction rules were found for estimating the likelihood of developing incident radiographic tibiofemoral osteoarthritis (OA) with rapid progression. Such a tool would enhance prognostic capability for clinicians and researchers. DESIGN: We used two longitudinal datasets to independently derive (Multicenter Osteoarthritis Study) and validate (Osteoarthritis Initiative) a prognostic clinical prediction rule for estimating the probability of incident rapidly progressing radiographic knee OA in the following 4-5 years. Eligible subjects had at least one knee with a Kellgren and Lawrence (K&L) graded tibiofemoral joint of 0 or 1. Several potential risk factors were examined including obesity, age, knee alignment, frequent knee symptoms, contralateral knee OA and knee injury history. Multiple logistic regression was used to identify significant predictors and area under the receiver operating characteristic curve (AUC) was used to assess discrimination. RESULTS: A total of 1690 subjects participated in the derivation and 2422 subjects participated in the validation of the clinical prediction rule. The multivariable model displayed good discrimination with AUC of 0.79 in the derivation dataset and 0.81 in the validation dataset. CONCLUSIONS: Persons with contralateral knee OA, a baseline index knee OA grade of 1, higher body mass index (BMI) and higher baseline Western Ontario and McMaster Universities arthritis index total scores were more likely to develop K&L grade of 3 or 4 within 5 years. Frequent knee symptoms at baseline were not a significant predictor. The prediction rule and nomogram can assist clinicians in estimating the probability of rapidly progressing radiographic knee OA and the nomogram can assist researchers conducting epidemiologic studies and clinical trials. PMID- 27390032 TI - 20 Years of insulin lispro in pediatric type 1 diabetes: a review of available evidence. AB - BACKGROUND: Insulin lispro, the first rapid-acting insulin analog, was developed 20 years ago and has been studied in multiple situations and various populations. OBJECTIVE: To review the literature on the use of insulin lispro in children, adolescents, and young adults. PATIENTS: Children, adolescents, and young adults with type-1-diabetes. METHODS: One hundred and twenty-two relevant publications, identified by a systematic (MEDLINE) and manual literature search, were reviewed. RESULTS: Multiple daily injection (MDI) treatment with insulin lispro or other rapid-acting insulins, mainly using neutral protamine Hagedorn (NPH) insulin as the basal component, was associated with reduced postprandial glucose excursions, similar or improved HbA1c levels, and similar or reduced risks of severe hypoglycemia when compared with regular human insulin across all age-groups. Continuous subcutaneous insulin infusion (CSII)-treatment with insulin lispro also showed similar or improved glycemic control vs. MDI- or other CSII-regimens across all age-groups, without increasing the rate of severe hypoglycemia. The other two more recently developed rapid-acting insulins (aspart, glulisine) demonstrated non-inferiority to lispro on HbA1c. Long-term observational studies and real-life experience indicate that the increasing use of optimized MDI- and CSII-regimens with insulin lispro was associated with improvements in overall glycemic control. CONCLUSIONS: For almost 20 years, rapid-acting insulins, in particular insulin lispro as the first-in-class, have contributed to broadening the treatment options for the unique needs of pediatric patients with type-1 diabetes across all age-groups, and have enabled more physiological insulin administration. Now widely used, they have allowed pediatric patients to safely reach better glycemic control, with more flexibility in their daily lives. PMID- 27390033 TI - Fear of falling, but not gait impairment, predicts subjective memory complaints in cognitively intact older adults. AB - AIM: Understanding the risk factors for developing subjective memory complaints (SMC) could help with early screening and treatment for cognitive impairment. The aim of the present study was to explore the risk factors for developing SMC, by focusing on gait-related variables. METHODS: A total of 406 community-dwelling older adults aged 65-85 years without impending cognitive impairment participated in baseline and 1-year follow-up evaluations. A comprehensive evaluation was carried out, and included gait speed and fear of falling (FoF) assessments, and the Montreal Cognitive Assessment test. Logistic regression analyses were carried out to independently evaluate the risk factors at baseline and follow-up evaluations. RESULTS: At baseline, 45.1% of older adults had SMC. The presence of SMC at baseline was associated with being female, subjective hearing loss and FoF. Of 223 participants who did not report SMC at baseline, 48 had newly developed SMC at follow up (21.5%). The significant predictors for developing SMC were being female and FoF, but not gait speed, and were independent of depression symptoms. The Montreal Cognitive Assessment total score at baseline was a marginally significant predictor for developing SMC at follow up (P = 0.06), but a lower score in the language domain was a significant predictor in further analysis. CONCLUSIONS: FoF was a significant risk for future development of SMC, suggesting that FoF might reflect the risk of cognitive impairment at an earlier stage, or that FoF and SMC could share the same basis of anxiety for daily activities. The mechanisms and consequence of this longitudinal relationship require further study. Geriatr Gerontol Int 2017; 17: 1125-1131. PMID- 27390034 TI - Causes and consequences of spatial variation in sex ratios in a declining bird species. AB - Male-biased sex ratios occur in many bird species, particularly in those with small or declining populations, but the causes of these skews and their consequences for local population demography are rarely known. Within-species variation in sex ratios can help to identify the demographic and behavioural processes associated with such biases. Small populations may be more likely to have skewed sex ratios if sex differences in survival, recruitment or dispersal vary with local abundance. Analyses of species with highly variable local abundances can help to identify these mechanisms and the implications for spatial variation in demography. Many migratory bird species are currently undergoing rapid and severe declines in abundance in parts of their breeding ranges and thus have sufficient spatial variation in abundance to explore the extent of sex ratio biases, their causes and implications. Using national-scale bird ringing data for one such species (willow warbler, Phylloscopus trochilus), we show that sex ratios vary greatly across Britain and that male-biased sites are more frequent in areas of low abundance, which are now widespread across much of south and east England. These sex ratio biases are sufficient to impact local productivity, as the relative number of juveniles caught at survey sites declines significantly with increasing sex ratio skew. Sex differences in survival could influence this sex ratio variation, but we find little evidence for sex differences in survival increasing with sex ratio skew. In addition, sex ratios have become male-biased over the last two decades, but there are no such trends in adult survival rates for males or females. This suggests that lower female recruitment into low abundance sites is contributing to these skews. These findings suggest that male biased sex ratios in small and declining populations can arise through local scale sex differences in survival and dispersal, with females recruiting disproportionately into larger populations. Given the high level of spatial variation in population declines and abundance of many migratory bird species across Europe at present, male-biased small populations may be increasingly common. As singing males are the primary records used in surveys of these species, and as unpaired males often sing throughout the breeding season, local sex ratio biases could also be masking the true extent of these population declines. PMID- 27390035 TI - Systematic design of membership functions for fuzzy-logic control: A case study on one-stage partial nitritation/anammox treatment systems. AB - A methodology is developed to systematically design the membership functions of fuzzy-logic controllers for multivariable systems. The methodology consists of a systematic derivation of the critical points of the membership functions as a function of predefined control objectives. Several constrained optimization problems corresponding to different qualitative operation states of the system are defined and solved to identify, in a consistent manner, the critical points of the membership functions for the input variables. The consistently identified critical points, together with the linguistic rules, determine the long term reachability of the control objectives by the fuzzy logic controller. The methodology is highlighted using a single-stage side-stream partial nitritation/Anammox reactor as a case study. As a result, a new fuzzy-logic controller for high and stable total nitrogen removal efficiency is designed. Rigorous simulations are carried out to evaluate and benchmark the performance of the controller. The results demonstrate that the novel control strategy is capable of rejecting the long-term influent disturbances, and can achieve a stable and high TN removal efficiency. Additionally, the controller was tested, and showed robustness, against measurement noise levels typical for wastewater sensors. A feedforward-feedback configuration using the present controller would give even better performance. In comparison, a previously developed fuzzy-logic controller using merely expert and intuitive knowledge performed worse. This proved the importance of using a systematic methodology for the derivation of the membership functions for multivariable systems. These results are promising for future applications of the controller in real full-scale plants. Furthermore, the methodology can be used as a tool to help systematically design fuzzy logic control applications for other biological processes. PMID- 27390036 TI - Determination of the fractions of syntrophically oxidized acetate in a mesophilic methanogenic reactor through an (12)C and (13)C isotope-based kinetic model. AB - In order to accurately describe the carbon flow in anaerobic digestion processes, this work investigates the acetate degradation pathways through the use of stable carbon isotope analysis and a mathematical model. Batch assays using labeled (13)C acetate were employed to distinguish the acetate consumption through methanogenic Archaea and acetate-oxidizing Bacteria. Suspended and sessile biomass, with over 400 days of retention time, from a mesophilic (36.5 degrees C) upflow anaerobic filter was used as inocula in these assays. A three-process model for acetoclastic methanogenesis and syntrophic acetate oxidation (SAO) was developed to allow for a precise quantification of the SAO contribution. The model distinguishes carbon atoms in light and heavy isotopes, (12)C and (13)C, respectively, which permitted the simulation of the isotope ratios variation in addition to gas production, gas composition and acetate concentrations. The model indicated oxidized fractions of acetate between 7 and 18%. Due to the low free ammonia inhibition potential for the acetoclastic methanogens in these assays these findings point to the biomass retention times as a driven factor for the SAO pathway. The isotope-based kinetic model developed here also describes the delta(13)C variations in unlabeled assays accurately and has the potential to determine biological (13)C fractionation factors. PMID- 27390038 TI - Fusaric acid induces mitochondrial stress in human hepatocellular carcinoma (HepG2) cells. AB - Fusarium spp are common contaminants of maize and produce many mycotoxins, including the fusariotoxin fusaric acid (FA). FA is a niacin related compound, chelator of divalent cations, and mediates toxicity via oxidative stress and possible mitochondrial dysregulation. Sirtuin 3 (SIRT3) is a stress response deacetylase that maintains proper mitochondrial function. We investigated the effect of FA on SIRT3 and oxidative and mitochondrial stress pathways in the hepatocellular carcinoma (HepG2) cell line. We determined FA toxicity (24 h incubation; IC50 = 104 MUg/ml) on mitochondrial output, cellular and mitochondrial stress responses, mitochondrial biogenesis and markers of cell death using spectrophotometry, luminometry, qPCR and western blots. FA caused a dose dependent decrease in metabolic activity along with significant depletion of intracellular ATP. FA induced a significant increase in lipid peroxidation, despite up-regulation of the antioxidant transcription factor, Nrf2. FA significantly decreased expression of SIRT3 mRNA with a concomitant decrease in protein expression. Lon protease was also significantly down-regulated. FA induced aberrant mitochondrial biogenesis as evidenced by significantly decreased protein expressions of: PGC-1alpha, p-CREB, NRF1 and HSP70. Finally, FA activated apoptosis as noted by the significantly increased activity of caspases 3/7 and also induced cellular necrosis. This study provides insight into the molecular mechanisms of FA (a neglected mycotoxin) induced hepatotoxicity. PMID- 27390037 TI - Anti-angiogenic effects of novel cyclin-dependent kinase inhibitors with a pyrazolo[4,3-d]pyrimidine scaffold. AB - BACKGROUND AND PURPOSE: Cyclin-dependent kinase 5 (CDK5) has recently emerged as an attractive target in several tumour entities. Inhibition of CDK5 has been shown to have anti-angiogenic effects in vitro and in vivo. However, potent inhibitors of CDK5, which can be applied in vivo, are still scarce. We have recently developed a new series of 5-substituted 3-isopropyl-7-[4-(2 pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines that show a preference for inhibiting CDK5 and tested them in vitro and in vivo in a murine model of hepatocellular carcinoma. EXPERIMENTAL APPROACH: All compounds were initially examined for effects on proliferation of HUVECs. The most potent compounds were then tested on migration, and one of them, LGR2674, was selected for assessing effects on nuclear fragmentation, cell cycle, cell viability and metabolic activity. Furthermore, LGR2674 was tested in a tube formation assay and in vivo in a murine model of hepatocellular carcinoma, induced by s.c. injection of HUH7 cells (measurement of in vivo toxicity, tumour vascularization, tumour cell proliferation and tumour size). KEY RESULTS: LGR2674 showed an EC50 in the low nanomolar range in the proliferation and migration assays. Cytotoxic effects started at 50 nM, a concentration that did not influence the cell cycle. In vivo, LGR2674 was well tolerated and caused a clear reduction in vessel density in the tumours; also tumour cell proliferation was inhibited and tumour growth retarded. CONCLUSIONS AND IMPLICATIONS: Pyrazolo[4,3-d]pyrimidine is a novel scaffold for the development of potent CDK inhibitors with in vivo potential. Such structures are good candidates for broadening our pharmacological arsenal against various tumours. PMID- 27390039 TI - Intraspecific variation in growth, morphology and toxin quotas for the cyanobacterium, Cylindrospermopsis raciborskii. AB - Cylindrospermopsis raciborskii is a bloom forming cyanobacterium with complex population dynamics and toxicity. In January of 2013 a single sample was collected from surface waters in Lake Wivenhoe, Australia, and twenty-four individual trichomes were isolated. Each isolate exhibited differences in growth rate, toxin cell quota and morphology, in the absence of phylogenetic heterogeneity. This study demonstrates substantial intraspecific isolate variation within a small sample and this has implications for understanding the population dynamics of this species. PMID- 27390040 TI - Biological activities of Leptodeira annulata (banded cat-eyed snake) venom on vertebrate neuromuscular preparations. AB - The physiological properties of colubrid snake venoms are largely unknown and less frequently investigated. In this study, we assessed the enzymatic properties and biological activities of Leptodeira annulata (banded cat-eyed snake) venom, an opistoglyphous snake from Colombia. The proteolytic, phospholipase A2 and amidolytic activities are assessed using colorimetric assays and the biological activities were analyzed in avian and mammalian neuromuscular preparations. L. annulata venom caused neuromuscular blockade in chick biventer cervicis (BC) preparations (40+/- 15% and 50+/- 3% of twitch reduction for 30 and 100 MUg/ml, respectively; p < 0.05) following 120 incubation; 10 MUg/ml of venom did not induce blockade. There was a mild reduction in contracture response to exogenous acetylcholine (110 MUM) in BC preparations exposed to 10 and 30 MUg of venom/ml (~4% and ~32% of reduction, respectively, p > 0.05, n = 4) compared to basal values whereas the highest concentration (100 MUg/ml) abolished it after 120 min. The venom caused a significant reduction in contracture response elicited by KCl (~58 and ~90 of reduction for 30 and 100 MUg/ml, respectively, p < 0.05, n = 4). In mouse phrenic nerve-diaphragm (PND) preparations, L. annulata venom induced a progressive muscle membrane depolarization [from -85.9 +/- 1.6 mV (t0) to -72.2 +/- 2.9 mV (t120), p < 0.05, n = 4); the postsynaptic receptors remained functional as shown by carbachol-induced depolarization. The morphological analyses showed a concentration-dependent number of pathological states in muscle fibers from both BC and PND preparations pre-exposed to venom. The venom showed high proteolytic activity and low phospholipase A2 activity; there was no evidence for serine protease activity. These results indicate that the neuromuscular effect induced by L. annulata venom resulted from damaged muscle fibers that lead to the blockade of twitches response. The findings suggest that the myotoxicity might be related to the presence of metalloproteases in this venom. PMID- 27390041 TI - Quantification of bufadienolides in the poisons of Rhinella marina and Rhaebo guttatus by HPLC-UV. AB - Bufadienolides are the main active compounds in the Bufonidae family of frogs. Recent studies have demonstrated cytotoxic and/or antitumor activity in these molecules. A HPLC-DAD method was developed and validated to quantify three bufadienolides (telocinobufagin, marinobufagin and bufalin) in ethyl acetate extracts of the cane toad poison frogs and smooth-sided toad. The chromatographic analysis was performed on Phenomenex Luna C18 (250.0 * 4.6 mm, 5 MUm), using gradient elution with acetonitrile and water, at a flow rate of 1.0 mL min(-1) and detection at 296 nm. The method showed linearity (r > 0.999) and adequate recovery values (86%-111%). The limits of quantification of bufadienolides were 7.4 MUg mL(-1) for telocinobufagin, 4.2 MUg mL(-1) for marinobufagin and 4.0 MUg mL(-1) for bufalin. Intraday and interday values of the method were evaluated and presented standard deviation values lower than 5%. The method was successfully applied to quantify the bufadienolides in the venom extract of the cane toad, which showed a content of 60% of marinobufagin. The same method was not selective for the venom extract of the Rhaebo guttatus, despite being linear, accurate and precise, requiring the development of a technique that presents a greater selectivity. PMID- 27390042 TI - Patagonfibrase modifies protein expression of tissue factor and protein disulfide isomerase in rat skin. AB - Patagonfibrase is a hemorrhagic metalloproteinase isolated from the venom of the South American rear-fanged snake Philodryas patagoniensis, and is an important contributor to local lesions inflicted by this species. The tissue factor (TF) factor VIIa complex, besides triggering the coagulation cascade, has been demonstrated to be involved in inflammatory events. Our aim was to determine whether patagonfibrase affects the expression of TF and protein disulfide isomerase (PDI), an enzyme that controls TF biological activity, at the site of patagonfibrase injection, and thus if they may play a role in hemostatic and inflammatory events induced by snake venoms. Patagonfibrase (60 MUg/kg) was administered s.c. to rats, and after 3 h blood was collected to evaluate hemostasis parameters, and skin fragments close to the site of injection were taken to assess TF and PDI expression. Patagonfibrase did not alter blood cell counts, plasma fibrinogen levels, or levels of TF activity in plasma. However, by semiquantitative Western blotting, patagonfibrase increased TF expression by 2 fold, and decreased PDI expression by 3-fold in skin samples. In agreement, by immunohistochemical analyses, prominent TF expression was observed in the subcutaneous tissue. Thus, patagonfibrase affects the local expression of TF and PDI without inducing any systemic hemostatic disturbance, although that they may be involved in the local inflammatory events induced by hemorrhagic metalloproteinases. Once antivenom therapy is not totally effective to treat the local injury induced by snake venoms, modulation of the activity and expression of TF and/or PDI might become a strategy for treating snake envenomation. PMID- 27390043 TI - Corrigendum: A Versatile Multiple Target Detection System Based on DNA Nano assembled Linear FRET Arrays. PMID- 27390044 TI - New drugs in cutaneous T-cell lymphomas. AB - PURPOSE OF REVIEW: Currently, there are no curative therapies for cutaneous T cell lymphoma (CTCL), and consecutive treatments tend to be given until loss of response. There is an urgent need for new and improved therapies in CTCL to treat symptoms such as pruritus and painful skin lesions and prolong survival. This article reviews new drugs available for CTCL. RECENT FINDINGS: CTCL encompasses a group of T-cell neoplasms presenting in the skin without systemic involvement. Mycosis fungoides being the most common type and Sezary syndrome the leukaemic form. Treatment is dependent on stage and responses to previous therapy. Treatments are broadly divided into skin-directed therapies which are first-line for early stage disease and systemic therapy reserved for refractory or advanced stage CTCL. This article reviews mode of action, responses and adverse effects of new drugs being considered for CTCL. SUMMARY: Most drugs for CTCL have response rates between 30 and 40%, and response durations tend to be less than a year. As such new studies looking at drug combinations or as maintenance therapy in those with a response to previous therapy should be trialled and may offer improved quality of life and outcome in CTCL. PMID- 27390045 TI - RE: Regorafenib Also Can Cause Osteonecrosis of the Jaw. PMID- 27390046 TI - Response. PMID- 27390047 TI - Underreporting of Lyme and Other Tick-Borne Diseases in Residents of a High Incidence County, Minnesota, 2009. AB - Lyme disease (LD), anaplasmosis, babesiosis and other tick-borne diseases (TBDs) attributed to Ixodes ticks are thought to be widely underreported in the United States. To identify TBD cases diagnosed in 2009, but not reported to the Minnesota Department of Health (MDH), diagnostic and procedural billing codes suggestive of tick-borne diseases were used to select medical charts for retrospective review in medical facilities serving residents of a highly endemic county in Minnesota. Of 444 illness events, 352 (79%) were not reported. Of these, 102 (29%) met confirmed or probable surveillance case criteria, including 91 (26%) confirmed LD cases with physician-diagnosed erythema migrans (EM). For each confirmed and probable LD, probable anaplasmosis and confirmed babesiosis case reported to MDH in 2009, 2.8, 1.3, 1.2 and 1.0 cases were likely diagnosed, respectively. These revised estimates provide a more accurate assessment and better understanding of the burden of these diseases in a highly endemic county. PMID- 27390048 TI - Pharmacokinetic model analysis of interaction between phenytoin and capecitabine. AB - OBJECTIVE: Recent reports have shbown an increase in serum phenytoin levels resulting in phenytoin toxicity after initiation of luoropyrimidine chemotherapy. To prevent phenytoin intoxication, phenytoin dosage must be adjusted. We sought to develop a pharmacokinetic model of the interaction between phenytoin and capecitabine. METHODS: We developed the phenytoin-capecitabine interaction model on the assumption that fluorouracil (5-FU) inhibits cytochrome P450 (CYP) 2C9 synthesis in a concentration- dependent manner. The plasma 5-FU concentration after oral administration of capecitabine was estimated using a conventional compartment model. Nonlinear pharmacokinetics of phenytoin was modeled by incorporating the Michaelis-Menten equation to represent the saturation of phenytoin metabolism. The resulting model was fitted to data from our previously reported cases. RESULTS: The developed phenytoincapecitabine interaction model successfully described the profiles of serum phenytoin concentration in patients who received phenytoin and capecitabine concomitantly. The 50% inhibitory 5-FU concentration for CYP2C9 synthesis and the degradation rate constant of CYP2C9 were estimated to be 0.00310 ng/mL and 0.0768 day-1, respectively. This model and these parameters allow us to predict the appropriate phenytoin dosage schedule when capecitabine is administered concomitantly. CONCLUSIONS: This newly developed model accurately describes changes in phenytoin concentration during concomitant capecitabine chemotherapy, and it may be clinically useful for predicting appropriate phenytoin dosage adjustments for maintaining serum phenytoin levels within the therapeutic range. PMID- 27390049 TI - Advantage of population pharmacokinetic method for evaluating the bioequivalence and accuracy of parameter estimation of pidotimod. AB - OBJECTIVE: This study was aimed at exploring the accuracy of population pharmacokinetic method in evaluating the bioequivalence of pidotimod with sparse data profiles and whether this method is suitable for bioequivalence evaluation in special populations such as children with fewer samplings. Methods In this single-dose, two-period crossover study, 20 healthy male Chinese volunteers were randomized 1 : 1 to receive either the test or reference formulation, with a 1 week washout before receiving the alternative formulation. Noncompartmental and population compartmental pharmacokinetic analyses were conducted. Simulated data were analyzed to graphically evaluate the model and the pharmacokinetic characteristics of the two pidotimod formulations. Various sparse sampling scenarios were generated from the real bioequivalence clinical trial data and evaluated by population pharmacokinetic method. RESULTS: The 90% confidence intervals (CIs) for AUC0-12h, AUC0-infinity, and Cmax were 97.3 - 118.7%, 96.9 - 118.7%, and 95.1 - 109.8%, respectively, within the 80 - 125% range for bioequivalence using noncompartmental analysis. The population compartmental pharmacokinetics of pidotimod were described using a one-compartment model with first-order absorption and lag time. In the comparison of estimations in different dataset, the estimation of random three- and< fixed four-point sampling strategies can provide results similar to those obtained through rich sampling. The nonlinear mixed-effects model requires fewer data points. Moreover, compared with the noncompartmental analysis method, the pharmacokinetic parameters can be more accurately estimated using nonlinear mixed-effects model. CONCLUSIONS: The population pharmacokinetic modeling method was used to assess the bioequivalence of two pidotimod formulations with relatively few sampling points and further validated the bioequivalence of the two formulations. This method may provide useful information for regulating bioequivalence evaluation in special populations. PMID- 27390050 TI - Bioequivalence and adhesion evaluation of transdermal clonidine following a change in excipient supplier. AB - OBJECTIVE: To evaluate the bioequivalence (BE), safety, tolerability, and adhesion of Oppanol(r) polyisobutylene (PIB)-containing transdermal therapeutic system (TTS) formulation (test treatment, T) with VistanexTM PIB-containing TTS formulation (reference treatment, R) of clonidine. METHODS: This randomized, double-blind, 2-way crossover study comprised a 7-day treatment with 0.3 mg clonidine/24 h (T1/R1), a 7-day washout, and another 7-day treatment (R1/T1) period. After a 3-day washout period, subjects used T2 and R2 (each 0.1 mg clonidine/24 h) simultaneously in the 7-day adhesion phase. Primary endpoints were AUC0-168 and Cavg. Secondary endpoints were AUC0-infinity and Cmax. Additional endpoints included adhesion properties for all phases. For the primary endpoint, the geometric mean (gMean) ratios for test/reference treatment were calculated with BE defined as 90% confidence interval (CI) between 80 and 125%. RESULTS: 58 subjects (mean age, 41.3 years) received treatment (T1/R1, n = 29; R1/T1, n = 29); 55 completed the adhesion phase. BE criteria were met for the primary and secondary endpoints. Adjusted gMean ratios for T1/R1 were 102.3% (90% CI: 95.7%, 109.4%) for AUC0-168; 104.3% (90% CI: 98.4%, 110.5%) for Cavg; 102.8% (90% CI: 97.3%, 108.6%) for AUC0-infinity; and 104.0% (90% CI: 98.2%, 110.3%) for Cmax. Mean adhesion was greater than 90% for all four patch types when data from all assessment times were included. Most frequently reported adverse events were general disorders and local irritation. CONCLUSIONS: Clonidine Oppanol(r) PIB containing TTS formulation was bioequivalent to VistanexTM PIB-containing TTS formulation and had similar adhesive properties. Both doses and formulations of clonidine-TTS were well tolerated. PMID- 27390052 TI - An open-label, multiple-dose study to assess the pharmacokinetics and tolerability of sitagliptin/metformin fixed-dose combination (FDC) tablet in healthy Chinese adult subjects. AB - AIM: This study investigated the pharmacokinetics of sitagliptin and metformin after multiple oral doses of the sitagliptin/metformin fixed-dose combination (MK0431A) tablet in healthy Chinese volunteers. METHODS: This was a singlecenter, randomized study in 24 healthy adults. Subjects received twice-daily doses of MK0431A 50-mg/500-mg tablet and 50-mg/850-mg tablet for 7 days. Serial blood and urine samples were collected at predefined time points for bioassay of sitagliptin and metformin. Safety was assessed throughout the study. RESULTS: Based on consecutive trough concentrations, the steady states of sitagliptin and metformin were reached after twice-daily administration of MK0431A tablets for 5 days. After the last dose, the mean +/- SD (standard deviation) peak sitagliptin concentration of 167.3 - 22.52 and 174.1 +/- 22.16 ng/mL was reached in a median tmax of 2.25 - 3 hours. The mean +/- SD Cmax of metformin appeared in a median tmax of 1.75 - 2.25 hours at 888.3 +/- 195.19 and 1,337 +/- 269.19 ng/mL with MK0431A 50 mg/500 mg and 50 mg/850 mg, respectively Mean +/- SD AUC012h of sitagliptin was between 1,404 +/- 147.48 and 1,374 +/- 179.12 h*ng/mL, while mean +/- SD AUC0-12h of metformin were 6,015 +/- 854.98 and 8,587 +/- 1,715.93 h*ng/mL with MK0431A 50 mg/500 mg and 50 mg/850 mg, respectively. Approximately 75% sitagliptin and 40% metformin were excreted unchanged in the urine, corresponding to a renal clearance of 17.84 - 18.27 L/h for sitagliptin and 27.11 - 27.94 L/h for metformin. CONCLUSION: No clinically-significant pharmacokinetic difference was identified between Chinese and foreign healthy volunteers regarding sitagliptin and metformin with multiple doses of MK0431A tablets. The treatments were well tolerated. PMID- 27390051 TI - Effects of paclitaxel liposome and capecitabine in the treatment of advanced gastric cancer by clinical observation. AB - OBJECTIVE: To evaluate the clinical effectiveness and side effects of paclitaxel liposome and capecitabine in the treatment of 34 cases with advanced gastric cancer. METHOD: For 64 patients with advanced gastric cancer, 30 cases were treated with docetaxel, cisplatin, and 5-fluorouracil (DCF group, control group), and 34 cases were treated with paclitaxel liposome and capecitabine (PC group, experimental group). DCF group: 75 mg/m2 of docetaxel, d1; 20 mg/m2 of cisplatin, d1-5; 350 mg/m2 of 5-fluorouracil, 4 - 6 hours of intravenous drip, d1-5, a cycle of 21 days. PC group: 135 mg/m2 of paclitaxel liposome, d1; 2,000 mg/m2.d of capecitabine, oral dose of twice per day, d1-14, a cycle of 21 days. RESULT: CONTROL GROUP: the chemotherapy with a total of 122 cycles, with an average of 4.07 cycles; 2 cases of complete remission (CR), 12 cases of partial remission (PR), 7 cases of stable disease (SD), and 9 cases of development of progressive disease (PD); 46.7% of the immediate efficacy (remission rate (RR)), 70% of the disease control rate (DCR), 6.9 months of median PFS, and 12.5 months of median OS. Experimental group: the chemotherapy with a total of 169 cycles, with an average of 4.97 cycles; 14 cases of PR, 9 cases of SD, and 11 cases of PD; 46.7% of the immediate efficacy (RR), 70% of the disease control rate (DCR), 6.9 months of median progression-free survival (PFS), and 12.5 months of median overall survival (OS). There were no remarkable differences in RR, DCR, PFS curve, or OS curve for the two groups. The major toxicity of the two groups was hematological toxicity. The incidence of grade III - IV leucopenia in the control and experimental group was 56.7% and 17.6%, respectively. And the incidence of grade III - IV anemia was 13.3% and 2.9%, respectively. CONCLUSION: As an ideal schema in first-line therapy for advanced gastric cancer, paclitaxel liposome combined with capecitabine is generally well tolerated in clinical use, and is worth further extension. PMID- 27390053 TI - Microbiological contamination of the euro currency in Estonia. PMID- 27390054 TI - All government departments must tackle causes of ill health, say experts. PMID- 27390055 TI - The Effect of Current Low Back Pain on Volitional Preemptive Abdominal Activation During a Loaded Forward Reach Activity. AB - BACKGROUND: A volitional preemptive abdominal contraction (VPAC) supports trunk stability during functional activity. Pain-free individuals can sustain VPAC during function, but such has not been reported for individuals with current low back pain (cLBP). OBJECTIVE: To examine whether cLBP affects VPAC performance during a loaded forward reach (LFR) task. DESIGN: Observational crossover study. SETTING: Laboratory. PARTICIPANTS: A total of 18 controls and 17 subjects with cLBP with pain ratings of 1/10 to 4/10 on a visual analog scale. INTERVENTIONS: Transverse abdominis (TrA) thickness measurements were recorded by blinded researchers from M-mode ultrasound imaging during 4 conditions: (1) quiet standing without abdominal drawing-in maneuver (ADIM); (2) quiet standing with ADIM; (3) LFR without ADIM; and (4) LFR with ADIM. A physical therapist with 29 years of experience collected historical and examination data. MAIN OUTCOME MEASURES: TrA muscle thickness (mm). RESULTS: A 2 (group) * 2 (contraction) * 2 (reach) analysis of variance demonstrated a significant group * contraction interaction (F [1, 31] = 4.499, P = .04) where ADIM produced greater TrA thickness increases in PLBP subjects (2.18 mm) versus controls (1.36 mm). We observed a significant main effect for reach (F [1, 31] = 14.989, P < .001), where LFR activity produced a greater TrA thickness (6.15 +/- 2.48 mm) versus quiet standing (5.30 +/- 2.12 mm). CONCLUSIONS: Subjects with cLBP demonstrated a greater increase in TrA activation during ADIM versus controls. PMID- 27390056 TI - The Effect of Propulsion Style on Wrist Movement Variability During the Push Phase After a Bout of Fatiguing Propulsion. AB - BACKGROUND: Wheelchair propulsion has been linked to overuse injuries regardless of propulsion style. Many aspects of the arcing (ARC) and semicircular (SEMI) propulsion styles have been compared, but differences in intracycle movement variability, which have been linked to overuse injuries, have not been examined. OBJECTIVE: To explore how ARC and SEMI affect changes in intracycle wrist movement variability after a fatiguing bout of propulsion. DESIGN: Repeated measures crossover design. SETTING: Wheelchair rollers and wheelchair fatigue course in a research laboratory. PARTICIPANTS: Twenty healthy, nondisabled adult men without previous wheelchair experience. INTERVENTIONS: Participants learned ARC and SEMI and used each to perform a wheelchair fatigue protocol. MAIN OUTCOME MEASUREMENTS: Thirty seconds of propulsion on rollers were recorded by motion capture cameras before and after a fatigue protocol for each propulsion style on 2 testing days. Angular wrist orientations (flexion/extension and radial/ulnar deviation) and linear wrist trajectories (mediolateral direction) were computed, and intracycle movement variability was calculated as standard deviations of the detrended and filtered values during the push phase beginning and end. Paired samples t tests were used to compare ARC and SEMI based on the percent changes from pre- to postfatigue protocol. RESULTS: Both propulsion styles resulted in increased intracycle wrist movement variability postfatigue, but observed increases did not significantly differ between ARC and SEMI. CONCLUSIONS: This study evinces that intersubject variability exceeded average changes in intracycle wrist movement variability for both propulsion styles. Neither propulsion style resulting in a greater change in intracycle movement variability may suggest that no single propulsion style is ideal for everyone. The large intersubject variability may indicate that the propulsion style resulting in the smallest increase in intracycle movement variability after a fatiguing bout of propulsion may differ for each person and may help explain why wheelchair users self-select to use different propulsion styles. PMID- 27390057 TI - Evaluation of Innate Immunity Biomarkers on Admission and at Discharge From an Acute Heart Failure Episode. AB - BACKGROUND: The involvement of the immune system in heart failure (HF) has been demonstrated. Evidence shows that innate immunity can have a role in the remodeling process and progression of HF. With previous studies showing the prognostic value of some innate immunity markers and their relevance in this condition, we aim to evaluate how these markers vary on hospitalization due to an acute episode of HF and at discharge. METHODS: About 154 patients admitted with acute HF were prospectively recruited. Patients were evaluated on admission and at discharge from the hospital. Patients with infection were separately analyzed. Innate immunity, inflammatory, and cardiac biomarkers were measured and were compared between groups and between admission and discharge and with reference values of biological variation. RESULTS: Median patients' age was 78 years, and half of the patients were men. The median duration of hospitalization was 6 days. C3 and C4 protein levels significantly increased (P < 0.001) between admission and discharge, as well as eosinophils (P < 0.001) and BNP levels decreased (P < 0.001). Variation in all these variables was independent of infection and biological variation. CONCLUSION: Our results show that innate immunity markers such as C3 and C4 increase after treatment for acute HF, supporting the hypothesis that they can be involved in the resolution of the acute episode. PMID- 27390058 TI - Quantitative determination of buprenorphine, naloxone and their metabolites in rat plasma using hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry. AB - A rapid and sensitive LC-MS/MS method was developed and validated for the simultaneous determination of buprenorphine and its three metabolites (buprenorphine glucuronide, norbuprenorphine and norbuprenorphine glucuronide) as well as naloxone and its metabolite naloxone glucuronide in the rat plasma. A hydrophilic interaction chromatography column and a mobile phase containing acetonitrile and ammonium formate buffer (pH 3.5) were used for the chromatographic separation. Mass spectrometric detection was achieved by an electrospray ionization source in the positive mode coupled to a triple quadrupole mass analyzer. The calibration curves for the six analytes displayed good linearity over the concentration range 1.0 or 5.0-1000 ng/mL. The intra and inter-day precision (CV) ranged from 2.68 to 16.4% and from 9.02 to 14.5%, respectively. The intra- and inter-day accuracy (bias) ranged from -14.2 to 15.2% and from -9.00 to 4.80%, respectively. The extraction recoveries for all the analytes ranged from 55 to 86.9%. The LC-MS/MS method was successfully applied to a pharmacokinetic study of buprenorphine-naloxone combination in rats. PMID- 27390059 TI - Adaptive capacity indicators to assess sustainability of urban water systems - Current application. AB - Sustainability is commonly assessed along environmental, societal, economic and technological dimensions. A crucial aspect of sustainability is that inter generational equality must be ensured. This requires that sustainability is attained in the here and now as well as into the future. Therefore, what is perceived as 'sustainable' changes as a function of societal opinion and technological and scientific progress. A concept that describes the ability of systems to change is adaptive capacity. Literature suggests that the ability of systems to adapt is an integral part of sustainable development. This paper demonstrates that indicators measuring adaptive capacity are underrepresented in current urban water sustainability studies. Furthermore, it is discussed under which sustainability dimensions adaptive capacity indicators are lacking and why. Of the >90 indicators analysed, only nine are adaptive capacity indicators, of which six are socio-cultural, two technological, one economical and none environmental. This infrequent use of adaptive capacity indicators in sustainability assessments led to the conclusion that the challenge of dynamic and uncertain urban water systems is, with the exception of the socio-cultural dimension, not yet sufficiently reflected in the application of urban water sustainability indicators. This raises concerns about the progress towards urban water systems that can transform as a response variation and change. Therefore, research should focus on developing methods and indicators that can define, evaluate and quantify adaptive capacity under the economic, environmental and technical dimension of sustainability. Furthermore, it should be evaluated whether sustainability frameworks that focus on the control processes of urban water systems are more suitable for measuring adaptive capacity, than the assessments along environmental, economic, socio-cultural and technological dimensions. PMID- 27390060 TI - Climatological analysis of the mitigating effect of vegetation on the urban heat island of Milan, Italy. PMID- 27390061 TI - A meta-analysis and systematic review of the risks associated with childhood attention-deficit hyperactivity disorder on long-term outcome of arrests, convictions, and incarcerations. AB - The primary aim of this study was to systematically review and estimate the risk of arrests, convictions, and incarcerations associated with childhood Attention Deficit/Hyperactivity Disorder (ADHD) in long-term outcome studies. In addition, all included studies were qualitatively and systematically reviewed for predictors of long-term crimes. The databases Pubmed, PsycINFO and Embase were searched for all controlled studies that included children and adolescents (age 4 15) with ADHD who had been followed longitudinally and reported the frequency of arrests, convictions or incarcerations based on data from official sources. Using random-effects models, the relative risk (RR) with 95% confidence intervals (95% CI) was estimated. A total of 15,442 individuals with childhood ADHD from nine unique samples were included. Childhood ADHD was significantly associated with adolescent and adulthood arrests (RR: 2.2, 95% CI: 1.3-3.5), convictions (RR: 3.3, 95% CI: 2.1-5.2) and incarcerations (RR: 2.9, 95% CI: 1.9-4.3). Individuals with ADHD had a younger age at onset of antisocial involvement and an increased risk of criminal recidivism. The most frequently committed criminal offenses were theft, assault, drug- and weapon-related crimes. Early antisocial behavior problems, childhood maltreatment, sex, and IQ were identified as potentially relevant predictors for antisocial outcomes. The findings support a substantial long-term risk associated with ADHD for later antisocial involvement. Early intensive and specifically targeted multimodal intervention including psychosocial, and pharmacological treatment is warranted to alter these negative long-term developmental trajectories. PMID- 27390063 TI - IVF outcomes in average- and poor-prognosis infertile women according to the number of embryos transferred. AB - Outcome measures of IVF success, which account for effectiveness of IVF and perinatal outcome risks, have recently been described. The association between number of embryos transferred in average and poor-prognosis IVF patients, and the chances of having good or poor IVF and perinatal outcomes, was investigated. Good IVF and perinatal outcome was defined as the birth of a live, term, normal-weight infant (>=2500 g). Poor IVF and perinatal outcome was defined as no live birth or birth of a very low weight neonate (<1500 g) or severe prematurity (birth at <32 weeks gestation). Each neonate was analysed as a separate outcome. A total of 713 IVF cycles in 504 average and poor-prognosis patients from January 2010 to December 2013 were identified. The odds of having good IVF and perinatal outcomes increased by 28% for each additional embryo transferred. The odds of poor IVF and perinatal outcome decreased by 32% with an additional embryo transferred. The likelihood of live birth with good perinatal outcome in average- and poor prognosis patients after IVF increases with additional embryos being transferred. These data add to recently reported evidence in favour of multiple embryo transfer in older women and those with average or poor IVF prognosis. PMID- 27390062 TI - The mirror illusion's effects on body state estimation. AB - The mirror illusion uses a standard mirror to create a compelling illusion in which movements of one limb seem to be made by the other hidden limb. In this paper we adapt a motor control framework to examine which estimates of the body's configuration are affected by the illusion. We propose that the illusion primarily alters estimates related to upcoming states of the body (the desired state and the predicted state), with smaller effects on the estimate of the body state prior to movement initiation. Support for this proposal is provided both by behavioural effects of the illusion and by neuroimaging evidence from one neural region, V6A, that is critically involved in the mirror illusion and limb state estimation more generally. PMID- 27390064 TI - Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. AB - A library of 585 compounds built off a 7-azaindole core was evaluated for anti HIV-1 activity, and ten hits emerged with submicromolar potency and therapeutic index >100. Of these, three were identified as non-nucleoside reverse transcriptase (RT) inhibitors and were assayed against relevant resistant mutants. Lead compound 8 inhibited RT with submicromolar potency (IC50=0.73MUM) and also maintained some activity against the clinically important RT mutants K103N and Y181C (IC50=9.2, 3.5MUM) in cell-free assays. Free energy perturbation guided lead optimization resulted in the development of a compound with a two fold increase in potency against RT (IC50=0.36MUM). These data highlight the discovery of a unique scaffold with the potential to move forward as next generation anti-HIV-1 agents. PMID- 27390065 TI - Modification of existing antibiotics in the form of precursor prodrugs that can be subsequently activated by nitroreductases of the target pathogen. AB - The use of existing antibiotics in the form of prodrug followed by activation using enzymes of pathogenic origin could be a useful approach for antimicrobial therapy. To investigate this idea, a common antibiotic, sulfamethoxazole has been redesigned in the form of a prodrug by simple functional group replacement. Upon reductive activation by a type I nitroreductase from a pathogen, the drug displayed enhanced antimicrobial capacity. This strategy could improve the efficacy and selectively of antibiotics and reduce the incidence of resistance. PMID- 27390066 TI - Discovery of potent and selective inhibitors of human aminopeptidases ERAP1 and ERAP2 by screening libraries of phosphorus-containing amino acid and dipeptide analogues. AB - A collection of fifty phosphonic and phosphinic acids was screened for inhibition of ERAP1 and ERAP2, the human endoplasmic reticulum aminopeptidases. The cooperative action of these enzymes is manifested by trimming a variety of antigenic precursors to be presented on the cell surface by major histocompatibility class I. The SAR studies revealed several potent compounds, particularly among the phosphinic dipeptide analogues, that were strong inhibitors of ERAP2 (Ki=100-350nM). A wide structural diversity of the applied organophosphorus compounds, predominantly non-proteinogenic analogues, allowed identification of representatives selective toward only one form of ERAP. For example, N'-substituted alpha,beta-diaminophosphonates and phosphinates exhibited potency only toward ERAP2, which is in agreement with the P1 basic substrate oriented specificity. Such discriminating ligands are invaluable tools for elucidating the precise role of a particular aminopeptidase in the concerted function of antigen processing and in human diseases. PMID- 27390067 TI - Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor targeting small molecules for PET imaging. AB - Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93+/-0.44 and 2.80+/ 0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10+/-5 (n=4) and 22+/-14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers. PMID- 27390068 TI - Design and synthesis of 1H-pyrazolo[3,4-c]pyridine derivatives as a novel structural class of potent GPR119 agonists. AB - Design and synthesis of a novel class of 1H-pyrazolo[3,4-c]pyridine GPR119 receptor agonists are described. Lead compound 4 was identified through the ligand-based drug design approach. Modification of the left-hand aryl group (R(1)) and right-hand piperidine N-capping group (R(2)) led to the identification of compound 24 as a single-digit nanomolar GPR119 agonist. PMID- 27390069 TI - Pharmacological protection of mitochondrial function mitigates acute limb ischemia/reperfusion injury. AB - We describe several novel curcumin analogues that possess both anti-inflammatory antioxidant properties and thrombolytic activities. The therapeutic efficacy of these curcumin analogues was verified in a mouse ear edema model, a rat arterial thrombosis assay, a free radical scavenging assay performed in PC12 cells, and in both in vitro and in vivo ischemia/reperfusion models. Our findings suggest that their protective effects partially reside in maintenance of optimal mitochondrial function. PMID- 27390071 TI - Depressive Symptoms in Ophthalmology Patients. PMID- 27390070 TI - Fabricating of high-performance functional graphene fibers for micro-capacitive energy storage. AB - Although graphene is a typical two dimensional materials, it has converted to multi-dimensional materials with many unique properties. As an example, the one dimensional graphene fiber is fabricated by utilizing ionic liquid as coagulation and functional diamines as cross-linkers to connect graphene oxide layers. The fibers show excellent mechanical properties and superior electrical performance. The tensile strength of the resultant fibers reaches ~729 MPa after a super high temperature thermal annealing treatment at 2800 degrees C. Additionally, quasi solid-state flexible micro-capacitors are fabricated with promising result on energy storage. The device show a specific volumetric capacity as high as ~225 F/cm(3) (measured at 103.5 mA cm(-3) in a three-electrode cell), as well as a long cycle life of 2000 times. The initial results indicate that these fibers will be a good candidate to replace energy storage devices for miniaturized portable electronic applications. PMID- 27390072 TI - Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis. AB - A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3months, the change in IL-4 from baseline to 6months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets. PMID- 27390073 TI - Using Qualitative Methods to Understand Physical Activity and Weight Management Among Bangladeshis in New York City, 2013. AB - INTRODUCTION: South Asians experience high rates of cardiovascular disease and type 2 diabetes, coupled with low rates of reported physical activity. We report findings from a qualitative sub-study that was conducted in 2013 among Bangladeshi immigrants in New York City to understand factors that affect physical activity practices and weight management in this community. METHODS: Qualitative study participants were recruited from community-based settings. Sex specific focus groups were conducted by trained community health workers. Proceedings were audio-recorded for translation and transcription and coded using a constant comparative approach. Data were coded using Atlas.ti software. RESULTS: Six focus groups were completed with a final sample of 67 participants (63% male, 37% female). Mean participant age was 42 years; mean years of residence in the United States was 12. Key themes that emerged were beliefs about modesty and sex-separated facilities that may prevent women from engaging in physical activity. Distinctions were made between men and women about what constitutes exercise versus physical activity; religious prayer was considered to be health-promoting because of the movement involved. Other important themes that emerged were cultural dietary practices and evolving conceptions of healthy weight. CONCLUSION: Tailored interventions that take into account the cultural context of this growing community are needed. Findings may also provide insight into barriers to health promotion experienced by other US Muslim communities, which are growing rapidly. PMID- 27390074 TI - A Trial of the Efficacy and Cost of Water Delivery Systems in San Francisco Bay Area Middle Schools, 2013. AB - INTRODUCTION: US legislation requires that schools offer free drinking water where meals are served. However, little information is available about what types of water delivery systems schools should install to meet such requirements. The study objective was to examine the efficacy and cost of 2 water delivery systems (water dispensers and bottleless water coolers) in increasing students' lunchtime intake of water in low-income middle schools. METHODS: In 2013, twelve middle schools in the San Francisco Bay Area participated in a cluster randomized controlled trial in which they received 6 weeks of promotional activities, received provision of cups, and were assigned to 1 of 2 cafeteria water delivery systems: water dispensers or bottleless water coolers (or schools served as a control). Student surveys (n = 595) and observations examined the interventions' effect on students' beverage intake and staff surveys and public data assessed intervention cost. RESULTS: Analysis occurred from 2013 through 2015. Mixed effects logistic regression, accounting for clustering and adjustment for student sociodemographic characteristics, demonstrated a significant increase in the odds of students drinking water in schools with promotion plus water dispensers and cups (adjusted odds ratio = 3.1; 95% confidence interval, 1.4-6.7; P = .004) compared with schools with traditional drinking fountains and no cups or promotion. The cost of dispenser and bottleless water cooler programs was similar ($0.04 per student per day). CONCLUSION: Instead of relying on traditional drinking fountains, schools should consider installing water sources, such as plastic dispensers with cups, as a low-cost, effective means for increasing students' water intake. PMID- 27390075 TI - New Summary Measures of Population Health and Well-Being for Implementation by Health Plans and Accountable Care Organizations. AB - Health plans and accountable care organizations measure many indicators of patient health, with standard metrics that track factors such as patient experience and cost. They lack, however, a summary measure of the third leg of the Triple Aim, population health. In response, HealthPartners has developed summary measures that align with the recommendations of the For the Public's Health series of reports from the Institute of Medicine. (The series comprises the following 3 reports: For the Public's Health: Investing in a Healthier Future, For the Public's Health: Revitalizing Law and Policy to Meet New Challenges, and For the Public's Health: The Role of Measurement in Action and Accountability.) The summary measures comprise 3 components: current health, sustainability of health, and well-being. The measure of current health is disability-adjusted life years (DALYs) calculated from health care claims and death records. The sustainability of health measure comprises member reporting of 6 behaviors associated with health plus a clinical preventive services index that indicates adherence to evidence-based preventive care guidelines. Life satisfaction represents the summary measure of subjective well-being. HealthPartners will use the summary measures to identify and address conditions and factors that have the greatest impact on the health and well-being of its patients, members, and community. The method could easily be implemented by other institutions and organizations in the United States, helping to address a persistent need in population health measurement for improvement. PMID- 27390076 TI - Impact of pre-transplant bone marrow plasma cell percentage on post-transplant response and survival in newly diagnosed multiple myeloma. AB - We evaluated 1070 patients with newly diagnosed multiple myeloma, who completed a single line of induction therapy followed by autologous stem cell transplantation. Patients with pre-transplant <5% BMPC had a threefold likelihood of achieving stringent complete response (sCR) after transplant compared to those with BMPC >=5% (45.6% vs. 16.3%; p < 0.0001). The median progression-free survival and overall survival from transplant for patients with pre-transplant BMPC <5% and >=5% was 30.8 and 115.2 months compared to 20.8 and 74.1 months, respectively (p < 0.0001 for both comparisons). The effect of pre-transplant BMPC was most pronounced in patients achieving complete response or very good partial response after transplant. In conclusion, pre-transplant BMPC <5% is an important prognostic marker of long-term survival after transplant and should be routinely incorporated into pre-transplant risk stratification. PMID- 27390077 TI - Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis. AB - OBJECTIVE: Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohn's disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA. METHODS: Gene analysis by 16S ribosomal RNA amplicon sequencing was used to compare the microbial composition in ileal and colonic biopsy specimens from 27 patients with SpA (14 with microscopic bowel inflammation, 13 without) and 15 healthy control subjects (ileal samples from all 15 subjects and colonic samples from 6). Spearman's rank correlation tests were used to assess correlations of the microbial composition with disease activity measures. RESULTS: The intestinal inflammation status (histologically normal versus acute or chronic inflammation) was strongly associated with the mucosal microbiota profile of patients with SpA. In inflamed biopsy tissue, the detected bacterial community composition clustered separately from that in noninflamed biopsy tissue (P < 0.05 by permutational multivariate analysis of variance, using hierarchical clustering on Bray-Curtis distances). Interestingly, abundance of the genus Dialister was found to be positively correlated with the Ankylosing Spondylitis Disease Activity Score (Spearman's rho = 0.62, false discovery rate-corrected q < 0.01). This finding was further supported by the low frequency of Dialister observed in noninflamed ileal and colonic biopsy tissue from patients with SpA and healthy controls. CONCLUSION: These findings demonstrate a significant difference in the intestinal microbial composition in patients with SpA who have microscopic gut inflammation compared to those without microscopic gut inflammation. Moreover, Dialister may represent a potential microbial marker of disease activity in SpA. PMID- 27390078 TI - The aesthetic appeal of assistive technology and the economic value baby boomers place on it: A pilot study. AB - BACKGROUND: This pilot study aimed to understand the importance of assistive technology (AT) aesthetics on the intention to purchase, using grab rails as the example. Furthermore, the study explored the economic value consumers placed on aesthetic appeal. METHOD: Structured interviews were conducted with 25 participants, nine female, mean age 59; where seven grab rails were presented and feedback obtained on the level of appeal and 'willingness to pay'. Responses to open-ended and fixed response questions were transcribed by the interviewer during the interview and a qualitative content analysis conducted. RESULTS: Positive and negative terms in relation to aesthetics were used to describe appealing and unappealing grab rails; however, all grab rails were felt to have negative aesthetic aspects by at least five participants. Physical design and finish emerged as the two main themes regarding the appeal of the grab rail designs. Participants' 'willingness-to-pay' for appealing options was mixed, with both over and under valuations. The most likely grab rails to be purchased were considered both appealing and cost effective by participants. CONCLUSION: Aesthetic appeal plays an important role in acceptance and uptake of AT. Designers and manufacturers should be encouraged to provide appealing options as the study has shown consumers prefer aesthetically appealing grab rails. However, the challenge is creating more appealing designs, without increasing cost as consumers seem to not want to pay more for them. Furthermore, clinicians need to acknowledge the importance of aesthetics when recommending interventions and be familiar with a range of options to provide clients with more choice. PMID- 27390079 TI - Assuring the Capture of Standardized Nursing Data: A Call to Action for Chief Nursing Officers. PMID- 27390080 TI - Advanced Practice Nurses Interventions by Case Management in Barcelona's Primary Care. PMID- 27390081 TI - Sexual Assault Severity and Depressive Symptoms as Longitudinal Predictors of the Quality of Women's Sexual Experiences. AB - Depressive symptoms are one consequence of adult/adolescent sexual victimization (ASV) and are linked to sexual health. Female nonproblem drinkers (N = 419) with an ASV history participated in a one-year longitudinal study. Participants completed measures of lifetime ASV severity and four quarterly assessments of depressive symptoms, ASV severity, and sexual experience quality. Multilevel models revealed that depressive symptoms interacted with ASV severity: Women with low-lifetime ASV severity reported higher ratings of sexual pain as depressive symptoms increased. ASV reported during assessment months predicted sexual experience quality. Interventions to improve survivors' sexual experiences should consider incorporating treatment for depressive symptoms. PMID- 27390082 TI - Factors influencing health behaviors among active duty Air Force personnel. AB - BACKGROUND: Individual health behaviors affect whether U.S. Air Force (USAF) service members are fit and ready to deploy. PURPOSE: The purpose of this study was to understand health behaviors of USAF members to guide future interventions to reduce cardiovascular risks. METHODS: A qualitative descriptive study was conducted with a purposive sample of 24 active duty USAF participants. Conventional content analysis was used to derive data-driven themes that were compared with the Health Promotion Model (HPM). DISCUSSION: Participants defined health in a multifactorial way that covered physical, emotional, and spiritual dimensions. The three themes that contributed to participants' health behaviors addressed: "who I am," "what works for me," and the USAF culture. There was a poor fit between findings as expressed by these participants and the HPM. CONCLUSION: Although these findings were derived from a sample of USAF participants, the findings have implications for members of other military services. The findings also have relevance for nurses and other providers within the civilian work environments who can promote health and wellness by integrating a client's personal history into a plan for developing and sustaining a healthy lifestyle. PMID- 27390083 TI - Adequacy of Online Patient Information Resources on Gout and Potentially Curative Urate-Lowering Treatment. AB - OBJECTIVE: To assess the content and readability of online patient information resources against the current understanding of gout. METHODS: An online survey was undertaken using Google UK, USA, Australia, and Canada. Information was assessed for content and accuracy on 19 key points regarding core content for gout patient information resources. Readability was assessed using the Flesch Kincaid Reading Ease score. Fifteen randomly selected websites were reviewed by a blinded second observer. RESULTS: A total of 85 websites were selected. More than 50% of the websites provided no information or had inaccuracies regarding the pathogenesis of gout. Most websites contained information on dietary and lifestyle modifications for treating gout and did not emphasize urate-lowering therapy (ULT) and its potential for cure. Over 75% of the websites had no/inaccurate information on the role of ULT or prophylaxis for preventing gout attacks on starting ULT. The majority of websites were difficult to read, with information in 68% of the websites rated at least fairly difficult. CONCLUSION: Only a few web-based patient information resources provide accurate and easy-to read information on gout. This study will help physicians direct patients to currently reliable resources, but there is a need to improve many web-based patient information resources, which at present act as barriers to care. PMID- 27390084 TI - Cross-Cultural Invariance of the Mental Toughness Inventory Among Australian, Chinese, and Malaysian Athletes: A Bayesian Estimation Approach. AB - The aims of this study were to assess the cross-cultural invariance of athletes' self-reports of mental toughness and to introduce and illustrate the application of approximate measurement invariance using Bayesian estimation for sport and exercise psychology scholars. Athletes from Australia (n = 353, Mage = 19.13, SD = 3.27, men = 161), China (n = 254, Mage = 17.82, SD = 2.28, men = 138), and Malaysia (n = 341, Mage = 19.13, SD = 3.27, men = 200) provided a cross-sectional snapshot of their mental toughness. The cross-cultural invariance of the mental toughness inventory in terms of (a) the factor structure (configural invariance), (b) factor loadings (metric invariance), and (c) item intercepts (scalar invariance) was tested using an approximate measurement framework with Bayesian estimation. Results indicated that approximate metric and scalar invariance was established. From a methodological standpoint, this study demonstrated the usefulness and flexibility of Bayesian estimation for single-sample and multigroup analyses of measurement instruments. Substantively, the current findings suggest that the measurement of mental toughness requires cultural adjustments to better capture the contextually salient (emic) aspects of this concept. PMID- 27390085 TI - The complete mitochondrial genome of Choristoneura longicellana (Lepidoptera: Tortricidae) and phylogenetic analysis of Lepidoptera. AB - To better understand the diversity and phylogeny of Lepidoptera, the complete mitochondrial genome of Choristoneura longicellana (=Hoshinoa longicellana) was determined. It is a typical circular duplex molecule with 15,759bp in length, containing the standard metazoan set of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an A+T-rich region. All of the inferred tRNA secondary structures show the common cloverleaf pattern, with the exception of trnS1(AGN), which lacks the DHU arm. The rrnL of C. Longicellana is the longest in sequenced lepidopterans. C. Longicellana has the same gene order as all lepidopteran species currently available in GenBank. There are 5 overlapping regions ranging from 1bp to 8bp and 14 intergenic spacers ranging from 1bp to 48bp. In addition, there are four similar tandem macro-satellite regions with the lengths of 101bp, 98bp, 92bp, and 92bp respectively in the A+T-rich regions of C. longicellana. We sampled 89 species representing 13 superfamilies, and reconstructed their relationship among Lepidoptera by Bayesian Inference and Maximum Likelihood analysis. The topology of the two phylogenetic analysis trees is identical roughly, except for Cossoidea in different locations, the positions of Cossoidea, Copromorphoidea, Gelechioidea, Zygaenoidea were not determined based the limited sampling. (Geometroidea+(Noctuoidea+Bombycoidea)) form the Macrolepidoptera "core". Pyraloidea group with the "core" Macrolepidoptera. Papilionoidea are not Macrolepidoptera. The Hesperiidae (represent Hesperioidea) is nested in the Papilionoidea, and closely related to Pieridae and Papilionidae. The well-known relationship of (Nymphalidae+(Riodinidae+Lycaenidae)) is recovered in this paper. PMID- 27390086 TI - Downregulation of miR-18a induces CTGF and promotes proliferation and migration of sodium hyaluronate treated human corneal epithelial cells. AB - Properly controlled corneal epithelial wound healing is critical for health of cornea, which involves cell proliferation, migration, anchoring and differentiation. Sodium hyaluronate (SH) has been proven to exert beneficial pharmacological effect on corneal wound healing, though the underlying mechanism remained open to investigation. MicroRNAs (miRNAs) are small single-stranded RNAs that could bind to 3'UTR of mRNAs of target genes. The multi-target regulation of miRNAs may favor treatment of corneal wound given the complicated processes implicated in the healing process, which has inspired initiatives to develop miRNA therapy in corneal wound healing. In this light, we used miRNAs profiling to detect whether miRNAs are also implicated in the mechanism underlying the stimulatory effect of SH on corneal epithelial wound healing. We found miR-18a was most susceptible to SH treatment, the target prediction of which were enriched in a bunch of pathways implicated in corneal wound healing. Connective tissue growth factor (CTGF) was found to be overrepresented in most significant enriched pathways and was experimentally confirmed as a bona fide target of miR 18a, which modulated cell migration and proliferation of human corneal epithelial cells. PMID- 27390087 TI - The first attempt for the isolation of an intact mRNA for structure determination. AB - I review the history of the first mRNA which was isolated for the determination of its RNA sequence from Escherichia coli. PMID- 27390089 TI - The first complete mitochondrial genome of a Belostomatidae species, Lethocerus indicus, the giant water bug: An important edible insect. AB - Lethocerus indicus of the family Belostomatidae is one of the most preferred and delicious edible insects in different parts of South-East Asia including North East, India. The mitogenome of L. indicus represents the first complete mitogenome sequence of a Belostomatidae species in Heteroptera order. The mitogenome of L. indicus is 16,251bp and contains 37 genes including 13 protein coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a large non-coding region. The genome has a typical gene order which is identical to other Heteroptera species. All tRNAs exhibit the classic cloverleaf secondary structure except tRNASer (AGN). All the PCGs employ a complete translation termination codon either TAA or TAG except COII. The nucleotide composition showed heavy biased toward AT accounting to 70.9% of total mitogenome. The overall A+T content of L. indicus mitogenome was comparatively lower than some other Heteropteran bugs mitogenomes. The control region is divided into seven different parts which includes the putative stem loop, repeats, tandem repeats, GC and AT rich regions. The phylogenetic relationship based on maximum-likelihood method using all protein coding genes was congruent with the traditional morphological classification that Belostomatidae is closely related to Nepidae. The complete mitogenome sequence of L. indicus provides fundamental data useful in conservation genetics and aquaculture diversification. PMID- 27390088 TI - ErbB2 is required for cardiomyocyte proliferation in murine neonatal hearts. AB - It has been long recognized that the mammalian heart loses its proliferative capacity soon after birth, yet, the molecular basis of this loss of cardiac proliferation postnatally is largely unknown. In this study, we found that cardiac ErbB2, a member of the epidermal growth factor receptor family, exhibits a rapid and dramatic decline in expression at the neonatal stage. We further demonstrate that conditional ablation of ErbB2 in the ventricular myocardium results in upregulation of negative cell cycle regulators and a significant reduction in cardiomyocyte proliferation during the narrow neonatal proliferative time window. Together, our data reveal a positive correlation between the expression levels of ErbB2 with neonatal cardiomyocyte proliferation and suggest that reduction in cardiac ErbB2 expression may contribute to the loss of postnatal cardiomyocyte proliferative capacity. PMID- 27390090 TI - Continuous renal replacement therapy-the new treatment of seriously hyperglycemia. PMID- 27390092 TI - Travel and Border Health Measures to Prevent the International Spread of Ebola. AB - During the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC implemented travel and border health measures to prevent international spread of the disease, educate and protect travelers and communities, and minimize disruption of international travel and trade. CDC staff provided in-country technical assistance for exit screening in countries in West Africa with Ebola outbreaks, implemented an enhanced entry risk assessment and management program for travelers at U.S. ports of entry, and disseminated information and guidance for specific groups of travelers and relevant organizations. New and existing partnerships were crucial to the success of this response, including partnerships with international organizations, such as the World Health Organization, the International Organization for Migration, and nongovernment organizations, as well as domestic partnerships with the U.S. Department of Homeland Security and state and local health departments. Although difficult to assess, travel and border health measures might have helped control the epidemic's spread in West Africa by deterring or preventing travel by symptomatic or exposed persons and by educating travelers about protecting themselves. Enhanced entry risk assessment at U.S. airports facilitated management of travelers after arrival, including the recommended active monitoring. These measures also reassured airlines, shipping companies, port partners, and travelers that travel was safe and might have helped maintain continued flow of passenger traffic and resources needed for the response to the affected region. Travel and border health measures implemented in the countries with Ebola outbreaks laid the foundation for future reconstruction efforts related to borders and travel, including development of regional surveillance systems, cross-border coordination, and implementation of core capacities at designated official points of entry in accordance with the International Health Regulations (2005). New mechanisms developed during this response to target risk assessment and management of travelers arriving in the United States may enhance future public health responses. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014 west-africa/partners.html). PMID- 27390093 TI - Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer. AB - Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy. PMID- 27390094 TI - Sequence Analysis for Alternating Copolymers by MALDI-TOF-MS: Importance of Initiator Selectivity for Comonomer Pair. AB - A special initiator for metal-catalyzed living radical polymerization facilitates sequence analyses by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) of alternating copolymers from styrene and maleimide derivatives. The initiator is a malonate-based alkyl halide (DEMM-Br), in which two ester groups are attached on the carbon neighboring to bromide, and poor electron density of the radical species allows determination of next unit to the initiator in resultant alternating copolymers due to the selective initiation to styrene derivative. Thanks to the well-defined alpha-end group, sequence of the oligomeric products via radical copolymerization of PMS and EMI with DEMM-Br can be more simply analyzed by MALDI-TOF-MS, and indeed the following are clarified: the crossover propagation is almost perfectly controlled regardless of the injection ratio; a minor error event of the disordered alternating sequence containing St-St sequential unit could take place; the minor error can be suppressed with an excess amount of maleimide. PMID- 27390095 TI - Modifications to the Butterfly Graft Used to Treat Nasal Obstruction and Assessment of Visibility. AB - Importance: Graft visibility in the supratip region has been the main criticism of the butterfly graft. Because of the graft location, slightly unfavorable supratip fullness can occur, resulting in patient dissatisfaction with the cosmetic result. Objective: To describe the clinical outcomes and visibility of the butterfly graft after technique modifications. Design, Setting, and Participants: In this retrospective review of adults who had undergone primary or secondary rhinoplasty with butterfly grafting from July 1, 2013, through July 31, 2014, at a tertiary care center at an academic institution, an operative log and photographs were reviewed in an effort to analyze outcomes of butterfly graft use in rhinoplasty. Main Outcomes and Measures: Nasal obstruction and visibility of the butterfly graft. Results: Thirty-four patients were included in the case series (mean [SD] age, 46 [19.4] years; 23 women and 11 men). The mean (SD) length of the graft was 3.4 (0.5) cm, and the mean (SD) width was 0.9 (0.2) cm. A significant decrease was found in the Nasal Obstruction Symptoms Evaluation score after surgery (mean [SD] preoperative score, 69 [17]; mean [SD] postoperative score, 23 [24]; P < .001). In regard to appearance, 25 patients (74%) rated their appearance as improved or no changes, 6 (18%) as minimally worse, and 1 (3%) as much worse. Fifty-nine observers participated in the masked survey for the study. When the graft was present, observers detected it 59.7% (282 of 472 answers) of the time. When the graft was not present, its presence was suspected 36.5% (237 of 649 answers) of the time. Conclusions and Relevance: The modified butterfly graft is a longer and thinner graft than the originally described butterfly graft. It is still an effective tool in the treatment of nasal obstruction with acceptable visibility. In most cases, it is difficult for health care professionals to identify the presence of the graft. Level of Evidence: 4. PMID- 27390096 TI - The vanishing atrial mass. PMID- 27390097 TI - Three-Dimensional Surface-Enhanced Raman Scattering Substrate Fabricated Using Chemical Decoration of Silver Nanoparticles on Electrospun Polycarbonate Nanofibers. AB - In this work, a simple method via decoration of silver nanoparticles (AgNPs) on electrospun polycarbonate nanofibers (PCNFs) was proposed to prepare highly sensitive three-dimensional (3D) substrates for surface-enhanced Raman scattering (SERS) measurements. The method proposed in this work gave a high sensitive Ag@PCNFs substrate, which resulted from a successful production of high surface area of PCNFs with a high efficiency in the decoration of AgNPs. To produce PCNFs suitable for SERS application, parameters in fabrication of PCNFs were systematically examined and correlated with their corresponding scanning electron microscope (SEM) images. Examined parameters included the concentration of PC solution, the solvent to form PC solution, the applied voltage, and the rotating speed of a drum collector. Using the optimized condition, the bead-free PCNFs with a diameter in the range of 200-400 nm were successfully produced. To increase the efficiency in decoration of AgNPs, the surface properties of PNCFs were altered with an organic solvent, which was selected experimentally with guidance of Hildebrand solubility parameter. Results indicated that methanol was the most suitable solvent to effectively decorate AgNPs on PCNFs. By probing with para-hydroxythiophenol (pHTP), prepared SERS substrates of Ag@PCNFs provided an enhancement factor to the order of 7, which is at least an order of magnitude larger than the reported values in the literature for SERS substrates prepared with the electrospinning technique. PMID- 27390098 TI - The aging memory: Modulating epigenetic modifications to improve cognitive function. AB - Age-related cognitive decline is a major concern in society. Here, I discuss recent evidence that shows an age-related modulation of gene transcription by epigenetic modifications. Epigenetic modifications, such as histone acetylation, is unbalanced in aging, with an increase in histone deacetylation, that limits the expression of plasticity-related genes. By modifying the balance towards histone acetylation, histone deacetylase inhibitors present a new pharmacological approach to ameliorate age-related cognitive deficits. PMID- 27390099 TI - Simultaneous Determination of beta-Cypermethrin and Its Metabolite 3 Phenoxybenzoic Acid in Microbial Degradation Systems by HPLC-UV. AB - The wide use of pesticides in agriculture is necessary to guarantee adequate food production worldwide. However, pesticide residues have caused global concern because of their potential health risk to consumers. In this study, we could identify beta-cypermethrin (beta-CY) and its degradation product 3-phenoxybenzoic acid (3-PBA) by liquid chromatograph-mass spectrometry. Few studies on the simultaneous determination of beta-CY and its metabolites have been carried out so far; hence, we established a high-performance liquid chromatography method to determine the concentrations of both beta-CY and 3-PBA simultaneously in microbial degradation systems. In this study, a novel beta-CY degrading strain, Bacillus licheniformis B-1, was isolated from a tea garden soil, utilizing beta CY as a growth substrate. Good linear relationships between beta-CY and 3-PBA were observed and the concentrations of reference solutions were between 0.50 and 60.00 ug/mL. Satisfactory stability and intra- and interday precision were obtained. The limits of detection were 0.06 and 0.13 ug/mL for beta-CY and 3-PBA, respectively, and the corresponding limits of quantification were 0.21 and 0.34 ug/mL, respectively. Spiking recoveries for beta-CY varied from 98.38 to 105.80%, with relative standard deviations (RSDs) varying from 1.49 to 3.93%. Spiking recoveries for 3-PBA varied from 99.59 to 101.20%, with RSDs varying from 0.58 to 3.64%. The proposed method has advantages of simplicity, rapidity, high accuracy, good separation and reproducibility; thus, it is ideally suitable for simultaneous determination of beta-CY and 3-PBA in microbial degradation systems. PMID- 27390100 TI - Gas Chromatographic Method for the Quantitative Determination of a Hydrolytic Degradation Impurity in Busulfan Injectable Products. AB - An efficient and stability-indicating method has been developed and validated for the quantitative determination of tetrahydrofuran (THF), a hydrolytic degradation impurity, in Busulfan injectable pharmaceutical products by using gas chromatograph equipped with a liquid autosampler and a flame ionization detector. The chromatographic separation was performed on a fused silica capillary (Stabilwax; 60 m length * 0.32 mm i.d., 0.5 um film thickness) column. The methodology was validated in accordance with regulatory guidelines. The proposed method was found to be specific, stable, precise, linear, accurate, robust, and rugged in the concentration range from 4 to 1,080 ppm for THF. The developed method was successfully applied to determine the THF content in Busulfan injectable pharmaceutical products. PMID- 27390102 TI - GMC says it can't force doctors to disclose payments from drug companies. PMID- 27390101 TI - Regional Myelin and Axon Damage and Neuroinflammation in the Adult Mouse Brain After Long-Term Postnatal Vanadium Exposure. AB - Environmental exposure to vanadium occurs in areas of persistent burning of fossil fuels; this metal is known to induce oxidative stress and oligodendrocyte damage. Here, we determined whether vanadium exposure (3 mg/kg) in mice during the first 3 postnatal months leads to a sustained neuroinflammatory response. Body weight monitoring, and muscle strength and open field tests showed reduction of body weight gain and locomotor impairment in vanadium-exposed mice. Myelin histochemistry and immunohistochemistry for astrocytes, microglia, and nonphosphorylated neurofilaments revealed striking regional heterogeneity. Myelin damage involved the midline corpus callosum and fibers in cortical gray matter, hippocampus, and diencephalon that were associated with axonal damage. Astrocyte and microglial activation was identified in the same regions and in the internal capsule; however, no overt myelin and axon damage was observed in the latter. Double immunofluorescence revealed induction of high tumor necrosis factor (TNF) immunoreactivity in reactive astrocytes. Western blotting analysis showed significant induction of TNF and interleukin-1beta expression. Together these findings show that chronic postnatal vanadium exposure leads to functional deficit and region-dependent myelin damage that does not spare axons. This injury is associated with glial cell activation and proinflammatory cytokine induction, which may reflect both neurotoxic and neuroprotective responses. PMID- 27390104 TI - Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase. AB - Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID- 27390105 TI - Why do we need theories? AB - Theories organize knowledge and construct objectivity by framing observations and experiments. The elaboration of theoretical principles is examined in the light of the rich interactions between physics and mathematics. These two disciplines share common principles of construction of concepts and of the proper objects of inquiry. Theory construction in physics relies on mathematical symmetries that preserve the key invariants observed and proposed by such theory; these invariants buttress the idea that the objects of physics are generic and thus interchangeable and they move along specific trajectories which are uniquely determined, in classical and relativistic physics. In contrast to physics, biology is a historical science that centers on the changes that organisms experience while undergoing ontogenesis and phylogenesis. Biological objects, namely organisms, are not generic but specific; they are individuals. The incessant changes they undergo represent the breaking of symmetries, and thus the opposite of symmetry conservation, a central component of physical theories. This instability corresponds to the changes of the environment and the phenotypes. Inspired by Galileo's principle of inertia, the "default state" of inert matter, we propose a "default state" for biological dynamics following Darwin's first principle, "descent with modification" that we transform into "proliferation with variation and motility" as a property that spans life, including cells in an organism. These dissimilarities between theories of the inert and of biology also apply to causality: biological causality is to be understood in relation to the distinctive role that constraints assume in this discipline. Consequently, the notion of cause will be reframed in a context where constraints to activity are seen as the core component of biological analyses. Finally, we assert that the radical materiality of life rules out distinctions such as "software vs. hardware." PMID- 27390106 TI - In vitro metabolism of specific CYP2D and CYP3A opioid substrates using rat liver S9 fractions and mass spectrometry reveal a severe metabolic impairment with increasing age. AB - Codeine and oxycodone are opioids used to alleviate pain. The outcome of the treatment is ultimately related to their metabolism by Cytochromes P450 (CYPs). Depending on the drugs used, alterations in the metabolism of drugs by CYPs can lead to severe consequences including alterations in their efficacy, safety and toxicity. The objectives of this study were to develop a novel HPLC-MS/MS method capable of quantifying codeine and oxycodone along with specific metabolites using an isotopic dilution strategy and study the rate of formation of morphine (CYP2D), norcodeine (CYP3A), oxymorphone (CYP2D) and noroxycodone (CYP3A). The chromatographic separation was achieved using a Biobasic C18 100 * 1 mm column combined with an isocratic mobile phase composed of methanol and 10 mm ammonium acetate (40:60) at a flow rate of 75 MUL/min. The mass spectrometer was operating in scan mode MS/MS and the analytical range was set at 10-10 000 nm. The precision (RSD) and accuracy (RE) observed were 4.4-11.5 and -9.1-6.1% respectively. Liver S9 fractions from 3-, 6-, 12- and 18-month-old male Sprague Dawley rats were prepared and Michaelis-Menten parameters were determined. The derived maximum enzyme velocity suggested a rapid saturation of the CYP2D and CYP3A active sites in the liver S9 fractions of 18-month-old rats. Moreover, metabolic stabilities of codeine and oxycodone in rat liver S9 fractions were significantly greater for the 18-month-old rats. This study suggests that there is an impairment of CYP2D and CYP3A metabolism in aging rats. PMID- 27390108 TI - 2D:4D indicates phimosis risk: A study on digit ratio and early foreskin development. AB - BACKGROUND: Many researchers have adopted 2D:4D (second to fourth finger length ratio) as a noninvasive retrospective biomarker for prenatal androgen exposure in recent years. It is thought to be related to diverse traits including behavioral phenotypes, disease susceptibility, and development of urogenital system. OBJECTIVE: To examine the relationship between 2D:4D and early foreskin development. METHODS: We analyzed the digit ratio and foreskin condition in 176 cases (range 0-6years). The boys were divided into four groups according to their ages: group 1, neonates (below 28days, n=13); group 2, infants (1-12months, n=45); group 3, toddlers (1-2years old, n=42); group 4, preschool children (3 6years old, n=76). We measured the lengths of the second and fourth digits of the left and right hands. The foreskin status was classified into 4 types. Type I (phimosis), type II (partial phimosis), type III (adhesion of prepuce), type IV (normal). RESULTS: The phimosis rate was 92.3%, 82.2%, 45.2%, and 38.7% in group 1 to group 4. In contrast, the proportion of normal foreskin increased from 0% in neonates to 13.2% in preschool children. The percentage of higher level of foreskin development shows a downward trend with the increase of digits ratio, and as the age grows, the percentage of normal foreskin cases also increases. CONCLUSIONS: These results suggest that a higher R2D:4D (right hand 2D:4D) is a risk factor for phimosis in the early human development. Age is also a significant influence factor of foreskin conditions. Additional research is required to identify pathophysiologic mechanisms and to determine clinical significance. PMID- 27390110 TI - Aminophylline-associated irritable behaviour in preterm neonates. AB - AIM: This study investigated the effect of aminophylline on behaviour and autonomic function in the preterm period. METHOD: Subjects were preterm infants cared for in the Oita University hospital from August 2012 to October 2014. The group that was administered aminophylline (Am+) and the group that received no aminophylline (Am-) included 11 cases that exhibited a mean gestational age of 28weeks 5days and a mean birth weight of 1109g and 8 cases that exhibited a mean gestational age of 30weeks 5days and a mean birth weight of 1223g, respectively. Intravenous aminophylline was administered continuously at a dose of 4-6mg/kg/day followed by oral therapy when the infant suffered repetitive apnoea. Two-hour video recordings were obtained every 2weeks, and electrocardiograms were performed simultaneously. Onset-offset and tremulous movements in general movement (GM) optimality list were used as indices of behaviour. Autonomic functions were investigated via heart-rate and heart-rate variability measurements using frequency domain spectral analysis and the MemCalc method. We compared indices in 4 periods: 30-31, 32-33, 34-35 and 36-37weeks gestation. RESULTS: The Am+ group exhibited significantly low optimality of tremulous movements at 32-33weeks gestation. The autonomic parameters did not differ significantly between the Am+ and Am- groups. There was no significant correlation between GMs optimality score and serum theophylline concentration. CONCLUSION: Aminophylline administration was associated with transient irritable behaviour without autonomic changes in the preterm period. PMID- 27390109 TI - Safety of histamine-2 receptor blockers in hospitalized VLBW infants. AB - BACKGROUND: Histamine-2 receptor (H2) blockers are often used in very low birth weight infants despite lack of population specific efficacy and safety data. AIMS: We sought to describe safety and temporal trends in histamine-2 receptor (H2) blocker use in hospitalized very low birth weight (VLBW) infants. STUDY DESIGN: We conducted a retrospective cohort study using a clinical database populated by an electronic health record shared by 348 neonatal intensive care units in the United States. SUBJECTS: We included all VLBW infants without major congenital anomalies. OUTCOME MEASURES: We used multivariable logistic regression with generalizing estimating equations to evaluate the association between days of H2 blocker exposure and risk of: 1) death or necrotizing enterocolitis (NEC); 2) death or sepsis; and 3) death, NEC, or sepsis. RESULTS: Of 127,707 infants, 20,288 (16%) were exposed to H2 blockers for a total of 6,422,352days. Median gestational age for infants exposed to H2 blockers was 27weeks (25th 75th percentile 26, 29). H2 blocker use decreased from 18% of infants in 1997 to 8% in 2012 (p<0.001). On multivariable analysis, infants were at increased risk of the combined outcome of death, NEC, or sepsis on days exposed to H2 blockers (odds ratio=1.14) (95% confidence interval 1.08, 1.19). CONCLUSIONS: H2 blocker use is associated with increased risk of the combined outcome of death, NEC, or sepsis in hospitalized VLBW infants. PMID- 27390111 TI - Attentional bias training in girls at risk for depression. AB - BACKGROUND: This study examined, for the first time, whether attentional biases can be modified in adolescents at risk for depression. METHODS: The final sample consisted of 41 girls at familial risk for depression, who were randomly assigned to receive six sessions (864 trials) of real or sham attention bias training [Real attentional bias training (ABT) vs. Sham ABT]. Participants who received Real ABT completed a modified dot-probe task designed to train attention toward positive and away from negative facial expressions; in contrast, girls who received Sham ABT completed the standard dot-probe task. Attentional biases, self reported mood, and psychophysiological responses to stress were measured at pre- and post-training assessments. RESULTS: As expected, girls who received Real ABT, but not those who received Sham ABT, exhibited significant increases from pre- to post-training in their attention toward happy faces and away from sad faces. Moreover, adolescents who received Real ABT were buffered against the negative outcomes experienced by adolescents who received Sham ABT. Specifically, only adolescents who received Sham ABT experienced an increase in negative mood and a pre- to post-training increase in heart rate in anticipation of the stressor. CONCLUSIONS: The current findings provide the first experimental evidence that attentional biases can be modified in youth at risk for depression and further suggest that ABT modulates the heightened response to stress that is otherwise experienced by high-risk adolescents. PMID- 27390113 TI - Perovskite Photodetectors Operating in Both Narrowband and Broadband Regimes. AB - Photodetectors are designed, which operate in the broadband regime upon bottom illumination (from the indium tin oxide (ITO) side) and in the narrowband regime upon top illumination (from the air/perovskite side). The narrowband photodetectors show high external quantum efficiency of above 104 %. The operational spectrum of the photodetectors can also be tuned by adjusting the halide composition in the active material. PMID- 27390112 TI - Brief Report: Vitamin D Deficiency Is Associated With Endothelial Dysfunction and Increases Type I Interferon Gene Expression in a Murine Model of Systemic Lupus Erythematosus. AB - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD) and impaired endothelial repair. Although vitamin D deficiency is associated with increased CVD risk in the general population, a causal relationship has not been demonstrated. We aimed to determine whether vitamin D deficiency directly modulates endothelial dysfunction and immune responses in a murine model of SLE. METHODS: Vitamin D deficiency was induced in lupus-prone MRL/lpr mice by dietary restriction for 6 weeks. Endothelium-dependent vasorelaxation was quantified using aortic ring myography, and endothelial repair mechanisms were assessed by evaluating the phenotype and function of bone marrow endothelial progenitor cells (EPCs) and with the use of an in vivo Matrigel plug model. Lupus disease activity was determined by evaluating expression of interferon-stimulated genes (ISGs) in splenic tissue, positivity for serum autoantibodies, and renal histology. To validate the findings, expression of ISGs was also measured in whole blood from vitamin D deficient and vitamin D-sufficient patients with SLE. RESULTS: Vitamin D deficiency resulted in impaired endothelium-dependent vasorelaxation and decreases in neoangiogenesis without a change in the total number of EPCs. There were no differences in anti-double-stranded DNA titers, proteinuria, or glomerulonephritis (activity or chronicity) between vitamin D-deficient or sufficient mice. Vitamin D deficiency was associated with a trend toward increased ISG expression both in mice and in patients with SLE. CONCLUSION: These findings indicate that vitamin D deficiency is associated with hampered vascular repair and reduced endothelial function, and may modulate type I interferon responses. PMID- 27390114 TI - Two-dimensional hydrophilic interaction chromatography * reversed-phase liquid chromatography for the preparative isolation of potential anti-hepatitis phenylpropanoids from Salvia prattii. AB - Traditional Tibetan medicine is important for discovery of drug precursors. However, knowledge of the chemical composition of traditional Tibetan medicines is very limited due to the lack of appropriate chromatographic purification methods. In the present work, Salvia prattii was taken as an example, and an off line hydrophilic interaction liquid chromatography/reversed-phase liquid chromatography preparative method was developed for the purification of phenylpropanoids with high purity from a crude sample of Salvia prattii. Based on the separation results of four different chromatographic stationary phases, the first-dimensional preparation was performed on an XAmide preparative column with the crude sample concentration of 62.0 mg/mL, and five main fractions were obtained from the 12.4 g crude sample with a recovery of 54.8%. An XCharge C18 preparative column was applied in the second-dimensional preparation to further isolate the phenylpropanoids from the redissolved first-dimensional fractions with concentration of approximately 50.0 mg/mL. The purities of the phenylpropanoids isolated from the crude sample of Salvia prattii were higher than 98%, indicating that the method was efficient for the purification of phenylpropanoids with high purity from Salvia prattii. Additionally, this method showed great potential in the preparation of phenylpropanoids and can serve as a good example for the purification of phenylpropanoids from other plant materials. PMID- 27390115 TI - The limited utility of currently available venous thromboembolism risk assessment tools in gynecologic oncology patients. PMID- 27390116 TI - Predictors of Back Pain in Middle-Aged Women: Data From the Australian Longitudinal Study of Women's Health. AB - OBJECTIVE: Back pain causes greater disability worldwide than any other condition, with women more likely to experience back pain than men. Our aim was to identify modifiable risk factors for back pain in middle-aged women. METHODS: Women born between 1946 and 1951 were randomly selected from the national health insurance scheme database to participate in The Australian Longitudinal Study on Women's Health. Self-reported data on back pain in the last 12 months, and on weight, physical activity, and other sociodemographic factors, were collected in 1998, 2001, 2004, 2007, 2010, and 2013. In 1998, a total of 12,338 women completed the survey and 10,011 (74%) completed the 2013 survey. RESULTS: At baseline, median (range) age was 49.5 years (44.6-53.5 years), and 54% reported back pain. In multivariate analysis, baseline weight and depression were positive predictors of back pain over each 3-year survey interval and over the following 15 years, whereas participation in vigorous physical activity was protective. The effects of weight on back pain were most marked in women with a body mass index of >=25 kg/m2 . CONCLUSION: Back pain is common in middle-aged women. Increased weight, weight gain, and depression were independent predictors of back pain over 15 years, whereas participation in vigorous physical activity was protective. Targeting these lifestyle factors is an important area for future research on reducing the burden of back pain in middle-aged women. PMID- 27390117 TI - Failure to Disclose Conflicts of Interest. PMID- 27390118 TI - The Relationship between the Methylated Septin-9 DNA Blood Test and Stool Occult Blood Test for Diagnosing Colorectal Cancer in Taiwanese People. AB - BACKGROUND: Colorectal cancer (CRC) is a common and lethal disease in the world. There is an increasing number of cases in Taiwan and a higher rate at advanced stages. The immune fecal occult blood test (iFOBT) has been used as a screening method in Taiwan for years. A new novel diagnostic tool, the Methylated Septin-9 (MS-9) DNA blood test, had been reported to have high sensitivity and specificity for CRC detection. There are no available data in Taiwan, so we conducted this prospective randomized trial to investigate the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. METHODS: From July 1, 2012 to December 31, 2013, we prospectively selected 60 plasma samples from patients who were diagnosed with CRC and otherwise, the healthy group by colonoscopy in our hospital. Patients were divided into the CRC group and healthy group. CRC stages 0, I, II and stages III and IV were separately analyzed. We calculated the sensitivity and specificity of each group to determine the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. RESULTS: The results of the MS-9 DNA blood test for the 60 samples were divided into three groups, and the sensitivity as well as the specificity of the MS-9 DNA blood test to detect CRC were 47% and 89%, respectively. The results of iFOBT were also divided into three groups, and had higher sensitivity (84%) but lower specificity (55%) using iFOBT to detect CRC. Higher rates could be predicted to detect CRC if both the tests were positive. CONCLUSIONS: A combined MS-9 DNA blood test and iFOBT may help in a higher detection rate of CRC. It could be offered to individuals who are unwilling or unable to undergo colonoscopy. Further large prospective, randomized studies are needed in the future. PMID- 27390119 TI - Identification of five novel MHC class II alleles in cynomolgus macaques of Vietnamese origin. AB - We report here the identification of one Mafa-DPA1 and four Mafa-DQB1 novel alleles of Vietnamese cynomolgus macaques. PMID- 27390121 TI - Headache in recent onset hypothyroidism: Prevalence, characteristics and outcome after treatment with levothyroxine. AB - Objective The objective of this article is to analyze the features of headache attributed to hypothyroidism (HAH), evaluate the differences between groups with and without HAH, between "overt" and "subclinical" hypothyroidism groups, and evaluate outcomes after levothyroxine treatment. Methods Patients with hypothyroidism were selected in a cross-sectional study, followed prospectively for 12 months, and classified as subclinical or overt hypothyroidism. The patients were divided into two groups: with and without HAH. Results HAH was reported by 73/213 (34%) patients, involving the following areas: fronto-orbital (49%), temporal (37%), and posterior part of the head (15%). The HAH features were as follows: pulsatile (63%), four to 72 hours' duration (78%), unilateral (47%), nausea/vomiting (60%), and moderate-severe intensity (72%). Hypothyroidism symptomatology was similar in both groups, except for a greater frequency of hoarseness in the group with HAH. Migraine history was more frequent in the patients with HAH (53% vs 38%, p < 0.05). The frequency of HAH was similar both in overt and subclinical hypothyroidism. After levothyroxine treatment 78% reported a decrease in HAH frequency. Subclinical and overt hypothyroid patients reported a similar alleviation of their headaches. Conclusion Patients with HAH may present with unilateral, pulsatile, episodic pattern, and nausea/vomiting, which is at odds with the criteria for HAH established by ICHD 3 beta. Not all individuals responded to levothyroxine, and patients with the subclinical form of hypothyroidism benefit from this treatment. PMID- 27390122 TI - A perspective on interaction effects in genetic association studies. AB - The identification of gene-gene and gene-environment interaction in human traits and diseases is an active area of research that generates high expectation, and most often lead to high disappointment. This is partly explained by a misunderstanding of the inherent characteristics of standard regression-based interaction analyses. Here, I revisit and untangle major theoretical aspects of interaction tests in the special case of linear regression; in particular, I discuss variables coding scheme, interpretation of effect estimate, statistical power, and estimation of variance explained in regard of various hypothetical interaction patterns. Linking this components it appears first that the simplest biological interaction models-in which the magnitude of a genetic effect depends on a common exposure-are among the most difficult to identify. Second, I highlight the demerit of the current strategy to evaluate the contribution of interaction effects to the variance of quantitative outcomes and argue for the use of new approaches to overcome this issue. Finally, I explore the advantages and limitations of multivariate interaction models, when testing for interaction between multiple SNPs and/or multiple exposures, over univariate approaches. Together, these new insights can be leveraged for future method development and to improve our understanding of the genetic architecture of multifactorial traits. PMID- 27390123 TI - Carbon Dioxide Transformation in Imidazolium Salts: Hydroaminomethylation Catalyzed by Ru-Complexes. AB - The catalytic species generated by dissolving Ru3 (CO)12 in the ionic liquids 1-n butyl-3-methyl-imidazolium chloride or 1-n-butyl-2,3-dimethyl-imidazolium chloride are efficient multifunctional catalysts for: (a) reverse water-gas shift, (b) hydroformylation of alkenes, and (c) reductive amination of aldehydes. Thus the reaction of alkenes with primary or secondary amines (alkene/amine, 1:1) under CO2 /H2 (1:1) affords the hydroaminomethylations products in high alkene conversions (up to 99 %) and selectivities (up to 96 %). The reaction proceeds under relatively mild reaction conditions (120 degrees C, 60 bar=6 MPa) and affords selectively secondary and tertiary amines. The presence of amine strongly reduces the alkene hydrogenation competitive pathway usually observed in the hydroformylation of terminal alkenes by Ru complexes. The catalytic system is also highly active for the reductive amination of aldehydes and ketones yielding amines in high yields (>90 %). PMID- 27390124 TI - Barbara (Basia) Howells. PMID- 27390125 TI - Editorial: Subduing Lupus: Can Preclinical Autoimmune Disease Be Arrested? PMID- 27390126 TI - Antibiotic prescribing and expenditures in outpatient adults in Greece, 2010 to 2013: evidence from real-world practice. AB - We provide a representative analysis of antibiotic prescribing, identify factors associated with broad-spectrum antibiotic prescribing and assess the costs associated with antibiotic use in adult outpatients in Greece. Outpatient antibiotic prescriptions for patients older than 19 years between 2010 and 2013 in Greece were extracted from the IMS Health Xponent database. Prescribing rate and total cost for prescribed antibiotics were calculated. Multivariate logistic regression was used to identify factors related to broad-spectrum antibiotic prescribing. More than 20 million antibiotics were prescribed during the study period, an annual rate of 768 prescribed antibiotics per 1,000 adults. Overall, 33.5% of antibiotics were prescribed for acute respiratory tract infections (ARTIs) for which antibiotics are often not indicated. Macrolides (29.9%), cephalosporins (26.9%) and fluoroquinolones (21.0%) were the most commonly prescribed antibiotic classes. The majority (89.0%) of antibiotics were broad spectrum. Antibiotic expenditures were approximately EUR 185 million during the study period. Factors associated with broad-spectrum prescribing included older patient age, specialty pulmonologists or otorhinolaryngologists, training in eastern Europe, diagnosis of ARTI, acute diagnosis, and first episode of disease. Broad-spectrum antibiotic prescribing for ARTIs is common in adult Greek outpatients and frequently inappropriate. These data indicate the need for initiatives aiming to control antibiotic prescribing. PMID- 27390127 TI - Macroautophagy inhibition maintains fragmented mitochondria to foster T cell receptor-dependent apoptosis. AB - Mitochondrial dynamics and functionality are linked to the autophagic degradative pathway under several stress conditions. However, the interplay between mitochondria and autophagy upon cell death signalling remains unclear. The T-cell receptor pathway signals the so-called activation-induced cell death (AICD) essential for immune tolerance regulation. Here, we show that this apoptotic pathway requires the inhibition of macroautophagy. Protein kinase-A activation downstream of T-cell receptor signalling inhibits macroautophagy upon AICD induction. This leads to the accumulation of damaged mitochondria, which are fragmented, display remodelled cristae and release cytochrome c, thereby driving apoptosis. Autophagy-forced reactivation that clears the Parkin-decorated mitochondria is as effective in inhibiting apoptosis as genetic interference with cristae remodelling and cytochrome c release. Thus, upon AICD induction regulation of macroautophagy, rather than selective mitophagy, ensures apoptotic progression. PMID- 27390128 TI - Hormone-induced repression of genes requires BRG1-mediated H1.2 deposition at target promoters. AB - Eukaryotic gene regulation is associated with changes in chromatin compaction that modulate access to DNA regulatory sequences relevant for transcriptional activation or repression. Although much is known about the mechanism of chromatin remodeling in hormonal gene activation, how repression is accomplished is much less understood. Here we report that in breast cancer cells, ligand-activated progesterone receptor (PR) is directly recruited to transcriptionally repressed genes involved in cell proliferation along with the kinases ERK1/2 and MSK1. PR recruits BRG1 associated with the HP1gamma-LSD1 complex repressor complex, which is further anchored via binding of HP1gamma to the H3K9me3 signal deposited by SUV39H2. In contrast to what is observed during gene activation, only BRG1 and not the BAF complex is recruited to repressed promoters, likely due to local enrichment of the pioneer factor FOXA1. BRG1 participates in gene repression by interacting with H1.2, facilitating its deposition and stabilizing nucleosome positioning around the transcription start site. Our results uncover a mechanism of hormone-dependent transcriptional repression and a novel role for BRG1 in progestin regulation of breast cancer cell growth. PMID- 27390129 TI - Methods for Developing the American College of Rheumatology's Electronic Clinical Quality Measures. PMID- 27390130 TI - Effect of Secukinumab on Patient-Reported Outcomes in Patients With Active Ankylosing Spondylitis: A Phase III Randomized Trial (MEASURE 1). AB - OBJECTIVE: To evaluate the effect of secukinumab (interleukin-17A inhibitor) on patient-reported outcomes in patients with active ankylosing spondylitis (AS). METHODS: In this phase III study, 371 patients were randomized (1:1:1) to receive intravenous (IV) secukinumab 10 mg/kg at baseline and weeks 2 and 4 followed by subcutaneous (SC) secukinumab 150 mg every 4 weeks (IV->150 mg group), or SC secukinumab 75 mg every 4 weeks (IV->75 mg group), or placebo. Patient-reported outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI criteria for 50% improvement (BASDAI 50), Short Form 36 (SF-36) physical component summary (PCS) score and mental component summary (MCS) score, Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Bath Ankylosing Spondylitis Functional Index (BASFI), EuroQol 5-domain (EQ-5D) questionnaire, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Work Productivity and Activity Impairment-General Health questionnaire (WPAI-GH). RESULTS: At week 16, secukinumab IV->150 mg or IV->75 mg was associated with statistically and clinically significant improvements from baseline versus placebo in the BASDAI (-2.3 for both regimens versus -0.6; P < 0.0001 and P < 0.001, respectively), SF-36 PCS (5.6 for both regimens versus 1.0; P < 0.0001 and P < 0.001, respectively), and ASQoL (-3.6 for both regimens versus -1.0; P < 0.0001 and P < 0.001, respectively). Clinically significant improvements in the SF-36 MCS, BASFI, EQ-5D, and BASDAI 50 were observed with both secukinumab groups versus placebo at week 16; improvements were also observed in the FACIT-F and WPAI-GH. All improvements were sustained through week 52. CONCLUSION: Our findings indicate that secukinumab provides significant and sustained improvements in patient-reported disease activity and health-related quality of life, and reduces functional impairment, fatigue, and impact of disease on work productivity in patients with active AS. PMID- 27390131 TI - Extraction and Esterification of Low-Titer Short-Chain Volatile Fatty Acids from Anaerobic Fermentation with Ionic Liquids. AB - Ionic liquids can both act as a solvent and mediate esterification to valorize low-titer volatile fatty acids and generate organic solvents from renewable carbon sources including biowaste and CO2 . In this study, four phosphonium ionic liquids were tested for single-stage extraction of acetic acid from a dilute stream and esterification to ethyl acetate with added ethanol and heat. The esterification proceeded with a maximum conversion of 85.9+/-1.3 % after 30 min at 75 degrees C at a 1:1 stoichiometric ratio of reactants. Extraction and esterification can be tailored using mixed-anion ionic liquids; this is demonstrated herein using a common trihexyl(tetradecyl)phosphonium cation and a mixed chloride and bis(trifluoromethylsulfonyl)imide anion ionic liquid. As a further proof-of-concept, ethyl acetate was generated from an ionic liquid-driven esterification of an acetic acid extractant generated using CO2 as the only carbon source by microbial electrosynthesis. PMID- 27390132 TI - SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. AB - Mitochondria form a dynamic network that responds to physiological signals and metabolic stresses by altering the balance between fusion and fission. Mitochondrial fusion is orchestrated by conserved GTPases MFN1/2 and OPA1, a process coordinated in yeast by Ugo1, a mitochondrial metabolite carrier family protein. We uncovered a homozygous missense mutation in SLC25A46, the mammalian orthologue of Ugo1, in a subject with Leigh syndrome. SLC25A46 is an integral outer membrane protein that interacts with MFN2, OPA1, and the mitochondrial contact site and cristae organizing system (MICOS) complex. The subject mutation destabilizes the protein, leading to mitochondrial hyperfusion, alterations in endoplasmic reticulum (ER) morphology, impaired cellular respiration, and premature cellular senescence. The MICOS complex is disrupted in subject fibroblasts, resulting in strikingly abnormal mitochondrial architecture, with markedly shortened cristae. SLC25A46 also interacts with the ER membrane protein complex EMC, and phospholipid composition is altered in subject mitochondria. These results show that SLC25A46 plays a role in a mitochondrial/ER pathway that facilitates lipid transfer, and link altered mitochondrial dynamics to early onset neurodegenerative disease and cell fate decisions. PMID- 27390133 TI - Risk of Serious Infection in Juvenile Idiopathic Arthritis Patients Associated With Tumor Necrosis Factor Inhibitors and Disease Activity in the German Biologics in Pediatric Rheumatology Registry. AB - OBJECTIVE: To examine the effects of tumor necrosis factor inhibitors on the risk for serious infections and other influencing factors in a registry. METHODS: Patients exposed for the first time to etanercept, adalimumab, or methotrexate and serious infections were identified in the German Biologic Registry for Pediatric Rheumatology (BIKER) registry. Serious infection rates per 1,000 observation-years and relative risks were calculated. Cox regression identified risk factors and provided hazard ratios (HRs) for occurrence of infections. RESULTS: A total of 3,350 patients with 5,919 observation-years fulfilled the inclusion criteria for the study. The first biologic agents were etanercept (1,720 cases) and adalimumab (177 cases). A total of 1,453 patients were treated with methotrexate and no biologic agent. In total, 28 serious infections were reported in 26 patients (4.7 per 1,000 patient-years), 5 with methotrexate (1.6 per 1,000 patient-years), 21 with etanercept (8.1 per 1,000 patient-years), and 2 with adalimumab (9.7 per 1,000 patient-years). Significant univariate risk factors for infection were therapy with biologic agents, disease duration before therapy start, corticosteroid medication, nonbiologic premedications, higher clinical Juvenile Arthritis Disease Activity Score including maximal 10 joints (cJADAS10) at therapy start, and higher mean cJADAS10 during therapy. In multivariate Cox regression, only biologic therapy and cJADAS10 at therapy start remained significant. Risk for infection was increased by etanercept (univariate HR 6.0 [95% confidence interval (95% CI) 2.0-17.5]) or adalimumab (HR 7.3 [95% CI 1.3-40.0]) compared to methotrexate as well as by an elevated cJADAS10 at therapy start (HR 1.1 [95% CI 1.0-1.2] per unit increase). CONCLUSION: The total rate of serious infections reported in the BIKER registry seems low. Treatment with etanercept or adalimumab increases the risk for serious infection slightly, compared to methotrexate. Disease activity expressed by cJADAS10 appears to be an independent risk factor. PMID- 27390134 TI - Letter to the editor: Escherichia coli harbouring mcr-1 gene isolated from poultry not exposed to polymyxins in Brazil. PMID- 27390135 TI - Quantitative analysis of ripasudil hydrochloride hydrate and its impurities by reversed-phase high-performance liquid chromatography after precolumn derivatization: Identification of four impurities. AB - We report the development and validation of a stability-indicating reversed-phase high-performance liquid chromatography method with precolumn derivatization for the separation and identification of the impurities of ripasudil hydrochloride hydrate, a novel protein kinase inhibitor. 2,3,4,6-Tetra-O-acetyl-beta-d glucopyranosyl isothiocyanate was chosen as the derivatizing reagent and triethylamine was added as catalyst. 200 MUL sample solution (1 mg/mL), 600 MUL derivatizing reagent (1 mg/mL), and 200 MUL triethylamine solution (1%, v/v) were mixed and reacted at 40 degrees C for 30 min. The separation was achieved on an Inertsil C18 ODS-3 (250 mm * 4.6 mm, 5 MUm) column using mobile phases including 10 mmol monopotassium phosphate buffer (pH 3.0) and methanol in gradient mode. The column temperature was adjusted at 25 degrees C and the flow rate at 1 mL/min. The detection was carried out at 220 nm. Different precolumn derivatization conditions as well as the high-performance liquid chromatography conditions were optimized. Ripasudil hydrochloride hydrate and its four impurities were detected and quantitated, among which two new compounds were characterized. The proposed method was validated and proven to be selective, accurate, and precise and suitable for the quantitative analysis of ripasudil hydrochloride hydrate. PMID- 27390136 TI - Physical Activity in People With Mental Illness in Hong Kong: Application of the Health Belief Model. AB - Physical activity is associated with various health benefits for people with mental illness (PMI). Very few studies to date have examined the factors associated with physical activity among PMI in the Chinese context. The present study examined the factors related to physical activity using the health belief model and the association between physical activity and perceived health among 443 PMI in Hong Kong using stratified sampling. Results from the structural equation modeling showed that among all the factors of the health belief model, self-efficacy was significantly related to higher levels of physical activity, and perceived barriers were significantly related to lower levels of physical activity. In addition, physical activity was significantly related to better perceived health and fewer health needs. Interventions to promote physical activity among PMI should aim to increase their self-efficacy in initiating and adhering to physical activity and to remove barriers to physical activity. PMID- 27390137 TI - Thomas Oswald Candler. PMID- 27390138 TI - Reply. PMID- 27390139 TI - Editorial: Can Prevotella copri Be a Causative Pathobiont in Rheumatoid Arthritis? PMID- 27390140 TI - HoBi-Like Pestivirus and Its Impact on Cattle Productivity. AB - The clinical features and economic impact of the infection caused by an emerging group of pestiviruses, namely HoBi-like pestivirus, in a cattle herd of southern Italy are reported. In 2011, the virus was first associated with respiratory disease, causing an abortion storm after 1 year and apparently disappearing for the following 3 years after persistently infected calves were slaughtered. However, in 2014, reproductive failures and acute gastroenteritis were observed in the same herd, leading to a marked decrease of productivity. A HoBi-like strain closely related to that responsible for previous outbreaks was detected in several animals. Application of an intensive eradication programme, based on the detection and slaughtering of HoBi-like pestivirus persistently infected animals, resulted in a marked improvement of the productive performances. PMID- 27390141 TI - Reply to Bernard et al. PMID- 27390142 TI - Do We Need More Than 6 Weeks of Antimicrobial Treatment for Vertebral Osteomyelitis? PMID- 27390143 TI - Monogenic diabetes: Implementation of translational genomic research towards precision medicine. AB - Various forms of early onset non-autoimmune diabetes are recognized as monogenic diseases, each subtype being caused by a single highly penetrant gene defect at the individual level. Monogenic diabetes (MD) is clinically and genetically heterogeneous, including maturity onset diabetes of the young and infancy-onset and neonatal diabetes mellitus, which are characterized by functional defects of insulin-producing pancreatic beta-cells and hyperglycemia early in life. Depending on the genetic cause, MD differs in the age at diabetes onset, the severity of hyperglycemia, long-term diabetic complications, and extrapancreatic manifestations. In this review we discuss the many challenges of molecular genetic diagnosis of MD in the face of a substantial genetic heterogeneity, as well as the clinical benefit and cost-effectiveness of an early genetic diagnosis, as demonstrated by simulation models based on lifetime complications and treatment costs. We also discuss striking examples of proof-of-concept of genomic medicine, which have enabled marked improvement in patient care and long term clinical management. Recent advances in genome editing and pluripotent stem cell reprogramming technologies provide new opportunities for in vitro diabetes modeling and the discovery of novel drug targets and cell-based diabetes therapies. A review of these future directions makes the case for exciting translational research to further our understanding of the pathophysiology of early onset diabetes. PMID- 27390144 TI - Insulin Postconditioning Reduces Infarct Size in the Porcine Heart in a Dose Dependent Manner. AB - AIM: Insulin and glucose may have opposite effects when used to reduce ischemia reperfusion injury. When insulin is administered alone, feeding state determines tolerance and further induces metabolic and hormonal changes. Higher insulin doses are needed for similar activation of cardioprotective Akt signaling in the fed compared to the fasted pig heart. Thus, the aim of the study was to investigate the effects of 2 prespecified insulin doses on infarct size, apoptosis, metabolism, and cardiac function in a clinically relevant, randomized large animal model using conventional percutaneous catheter intervention techniques and including different fasting states. METHODS AND RESULTS: Twenty seven female pigs were subjected to 40-minute ischemia and 120-minute reperfusion. Pharmacological postconditioning with intracoronary infusions administered over 3 * 30 seconds was performed at immediate reperfusion. Animals were randomly assigned to 3 groups-preexperimental fasting and intracoronary saline ( controls), preexperimental fasting and 0.1U of insulin ( fasted Ins0.1U), and preexperimental feeding and 1.0U of insulin ( fed Ins1.0U). A significant reduction in infarct size was demonstrated in the fed Ins1.0U group ( P = .047) but not in the fasted Ins0.1U group ( P = .531) compared to controls (infarct size normalized to area at risk +/- standard deviation: controls 70.2% +/- 12.9%, fasted Ins0.1U 65.0% +/- 9.4%, and fed Ins1.0U 54.4% +/- 7.3%). Infarct limitation was associated with more uncleaved caspase-3 in the area of risk and the infarcted area, lower circulating free fatty acids, and less increase in heart rate during reperfusion. Fed animals had higher levels of glucose, carnitine, potassium, and normetanephrine and higher heart rate at baseline compared to controls. CONCLUSION: Insulin postconditioning reduced infarct size in the in vivo pig heart, but the beneficial effects were restricted to the highest dose, which is limited by side effects and can only be given to nonfasted animals. The finding challenges successful general use of insulin in the treatment of reperfusion injury in clinical acute myocardial infarction. PMID- 27390145 TI - Comparison of the Effects of Levosimendan Dobutamine and Vasodilator Therapy on Ongoing Myocardial Injury in Acute Decompensated Heart Failure. AB - BACKGROUND: Cardiac troponins (cTn) are reliable and the most sensitive biomarker in the setting of acute decompensated heart failure (ADHF). Acute decompensated heart failure is usually associated with worsening chronic heart failure, and it may be caused by ongoing minor myocardial cell damage that may occur without any reported precipitating factors. METHODS: We compared the short-term effect of levosimendan (LEV), dobutamine (DOB), and vasodilator treatment (nitroglycerin [NTG]) on myocardial injury with hemodynamic, neurohumoral, and inflammatory indicators. One hundred twenty-two patients with a mean age of 66 +/- 9 years were treated with LEV (n = 40), DOB (n = 42), and NTG (n = 40) and examined retrospectively. Blood samples (cTnI, N-terminal probrain natriuretic peptide [NT proBNP], highly sensitive C-reactive protein [HsCRP], and others), left ventricular ejection fraction (LVEF), systolic pulmonary artery pressure (sPAP), and 6-minute walk distance (6MWD) were compared before and after treatment. RESULTS: At admission, detectable levels of cTnI were observed in 53% of patients (>=0.05 ng/mL). Serial changes in the mean cTnI levels were not significantly different between the groups (LEV 0.04 +/- 0.01 to 0.03 +/- 0.01 ng/mL; DOB 0.145 +/- 0.08 to 0.08 +/- 0.03 ng/mL; NTG 0.1 +/- 0.03 to 0.09 +/- 0.02 ng/mL; overall P = .859). Favourable effects on the NT-proBNP, sPAP values, LVEF, 6MWD, and HsCRP were observed overall, especially in the LEV groups. CONCLUSION: Beneficial effects of short-term use of LEV, DOB, and NTG on ongoing myocardial injury were demonstrated. These findings can be attributed to the anti-ischemic properties as well as the hemodynamic, neurohumoral, and functional benefits from the positive inotropes, especially LEV, in patients with ADHF. PMID- 27390146 TI - Factors Related to Blood Hydroxychloroquine Concentration in Patients With Systemic Lupus Erythematosus. AB - OBJECTIVE: To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metabolite, N-desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE; lupus) receiving long term oral HCQ treatment. METHODS: SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical characteristics, laboratory values, and SLE Disease Activity Index (SLEDAI) scores were examined. The concentrations of HCQ and DHCQ ([HCQ] and [DHCQ]) were measured by liquid chromatography mass spectrometry, and the relationship between [HCQ], [DHCQ], and [HCQ]:[DHCQ] ratio to various factors was investigated. RESULTS: In total, 189 SLE patients receiving long-term HCQ treatment were included in the analysis. The median (interquartile range [IQR]) [HCQ] was 515 (IQR 353-720) ng/ml, the median [DHCQ] was 417 (IQR 266-591) ng/ml, and the median [HCQ]:[DHCQ] ratio was 1.3 (range 1.0-1.7). [HCQ] was closely associated with [DHCQ] (r = 0.81, P < 0.0001). The weight-adjusted oral HCQ dose was strongly associated with both [HCQ] (P < 0.001) and [DHCQ] (P < 0.001). Time since last dose was associated with [HCQ] (P < 0.001). No statistically significant association was found between renal function or smoking and [HCQ] or [DHCQ]. Use of additional immunosuppressants increased both [HCQ] and [DHCQ] after adjusting for possible confounders (P = 0.04 and P = 0.03, respectively). The lower SLEDAI score was significantly related to higher [HCQ], after adjusting for age, sex, weight-adjusted HCQ dose, time since last dose, number of other immunosuppressants, and smoking status (P = 0.007). CONCLUSION: Various factors affected blood levels of [HCQ], [DHCQ], or the [HCQ]:[DHCQ] ratio of SLE patients receiving long-term oral HCQ treatment. Notably, higher [HCQ] was associated with a lower SLEDAI score in our typical outpatient clinic population with lupus. PMID- 27390147 TI - Relations Between Autonomous Motivation and Leisure-Time Physical Activity Participation: The Mediating Role of Self-Regulation Techniques. AB - This study tested the predictive validity of a multitheory process model in which the effect of autonomous motivation from self-determination theory on physical activity participation is mediated by the adoption of self-regulatory techniques based on control theory. Finnish adolescents (N = 411, aged 17-19) completed a prospective survey including validated measures of the predictors and physical activity, at baseline and after one month (N = 177). A subsample used an accelerometer to objectively measure physical activity and further validate the physical activity self-report assessment tool (n = 44). Autonomous motivation statistically significantly predicted action planning, coping planning, and self monitoring. Coping planning and self-monitoring mediated the effect of autonomous motivation on physical activity, although self-monitoring was the most prominent. Controlled motivation had no effect on self-regulation techniques or physical activity. Developing interventions that support autonomous motivation for physical activity may foster increased engagement in self-regulation techniques and positively affect physical activity behavior. PMID- 27390148 TI - Life's arrow: the Epistemic Singularity. PMID- 27390149 TI - Incidence of Chronic Persistent Rheumatoid Arthritis and the Impact of Smoking: A Historical Twin Cohort Study. AB - OBJECTIVE: To assess the incidence of chronic persistent rheumatoid arthritis (RA) in a population-based cohort of twins and to determine the impact of smoking. METHODS: In a historical cohort study on twins born in 1920 to 1982, we identified 157 cases of RA among 45,280 responders (response rate 80%). Information on smoking was obtained by questionnaire and interview. A mixed effects Poisson regression model was used to estimate incidence rate ratios with age, sex, smoking duration, and smoking intensity as covariates. We used the SplitLexis procedure in the Epi R package to study a possible effect of period or cohort in addition to age on the variation of the incidence. RESULTS: The annual incidence of chronic persistent RA was 18.8 per 100,000 person-years, ages 15-73 years (females 25.2, males 12.0), increasing with age to a maximum at age 60 years in females and age 70 years in males. The incidence rate ratio among ever smoking patients was 1.96 (95% confidence interval [95% CI] 1.43-3.76), 1.93 (95% CI 1.00-3.7) after 30 pack-years, and 1.034 (P < 0.001) per year of smoking, implying a doubling of risk after 20 years regardless of sex and smoking intensity. We did not detect significant period or cohort effects. CONCLUSION: The incidence of chronic persistent RA is lower than the incidence figures reported in inception cohorts. Smoking duration, but not intensity, doubled the risk of RA after 20 years of smoking in both sexes. PMID- 27390151 TI - Recombinant Protein p30 for Serological Diagnosis of African Swine Fever by Immunoblotting Assay. AB - This article is devoted to the development and evaluation of the immunoblotting test system for serological diagnosis of African swine fever (ASF), based on the highly purified recombinant p30 of ASF virus (ASFV) strain Stavropol 01/08 (Stavropol 2008), representative of the ASFV currently circulating in the Russian Federation. The main project stages are as follows: (i) cloning of the central hydrophilic region of the ASFV gene CP204L (p30) into a prokaryotic vector; (ii) expression and chromatographic purification of the recombinant product p30 with thioredoxin and poly-histidine site (p30e1_TrxA_6xHis); (iii) development of the immunoblotting test system (Rec p30-IB) using the highly purified recombinant p30; and (iv) evaluation of Rec p30-IB using sera and organ samples from domestic pigs and wild boars experimentally or naturally infected by ASFV. Testing of the Rec p30-IB showed the diagnostic specificity and sensitivity of the assay to be 98.75% and 100.00%, respectively. High sensitivity of the Rec p30-IB allowed the detection of ASFV-specific antibodies in samples of organs of the immune system and blood sera, collected from domestic pigs and wild boars, starting from 6 to 8 days post-infection, regardless of virus virulence, seroimmunotype and geographic origin of the samples (East Europe, South Europe, West Europe, Central and south east Africa). PMID- 27390150 TI - Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate. AB - OBJECTIVE: To evaluate the efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). METHODS: Three hundred RA patients receiving stable doses of MTX were randomly assigned equally to receive immediate release ABT-494 at 3, 6, 12, or 18 mg twice daily, 24 mg once daily, or placebo for 12 weeks. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 12, as determined using the last observation carried forward method. RESULTS: At week 12, the proportion of ACR20 responses was higher with ABT-494 (62%, 68%, 80%, 64%, and 76% for the 3, 6, 12, 18, and 24 mg doses, respectively) than with placebo (46%) (using nonresponder imputation) (P < 0.05 for the 6, 12, and 24 mg doses). There was a significant dose-response relationship among all ABT-494 doses (P < 0.001). The proportions of patients achieving ACR50 and ACR70 responses were significantly higher for all ABT-494 doses (except the 12 mg dose for the ACR70 response) than for placebo, as were changes in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). Rapid improvement was demonstrated by significant differences in ACR20 response rates and changes in the DAS28-CRP for all doses compared with placebo at week 2 (the first postbaseline visit). The incidence of adverse events was similar across groups; most were mild, and infections were the most frequent. One serious infection (community-acquired pneumonia) occurred with ABT-494 at 12 mg. There were dose-dependent increases in high-density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, but the LDL cholesterol:HDL cholesterol ratios were unchanged through week 12. Mean hemoglobin levels remained stable at lower doses, but decreases were observed at higher doses. CONCLUSION: This study evaluated a broad range of doses of ABT-494 in RA patients with an inadequate response to MTX. ABT-494 demonstrated efficacy, with a safety and tolerability profile similar to that of other JAK inhibitors. PMID- 27390152 TI - Nina Avis Mellon. PMID- 27390153 TI - Early or delayed provision of an ankle-foot orthosis in patients with acute and subacute stroke: a randomized controlled trial. AB - OBJECTIVE: (1) To study the effects of providing ankle-foot orthoses in subjects with (sub)acute stroke; and (2) to study whether the point in time at which an ankle-foot orthosis is provided post-stroke (early or delayed) influences these effects. DESIGN: Randomized controlled trial. SETTING: Rehabilitation centre. SUBJECTS: Unilateral hemiparetic stroke subjects with indication for use of an ankle-foot orthosis and maximal six weeks post-stroke. INTERVENTIONS: Subjects were randomly assigned to: early provision (at inclusion; Week 1) or delayed provision (eight weeks later; Week 9). OUTCOME MEASURES: 10-metre walk test, 6 minute walk test, Timed Up and Go Test, stairs test, Functional Ambulation Categories, Berg Balance Scale, Rivermead Mobility Index and Barthel Index; assessed in Weeks 1, 3, 9 and 11. RESULTS: A total of 33 subjects were randomized (16 early, 17 delayed). Positive effects of ankle-foot orthoses were found two weeks after provision, both when provided early (significant effects on all outcomes) or delayed (Berg Balance Scale p = 0.011, Functional Ambulation Categories p = 0.008, 6-minute walk test p = 0.005, Timed Up and Go Test p = 0.028). Comparing effects after early and delayed provision showed that early provision resulted in increased levels of improvement on Berg Balance Scale (+5.1 points, p = 0.002), Barthel Index (+1.9 points, p = 0.002) and non-significant improvements on 10-metre walk test (+0.14 m/s, p = 0.093) and Timed Up and Go Test (-5.4 seconds, p = 0.087), compared with delayed provision. CONCLUSIONS: We found positive effects of providing ankle-foot orthoses in (sub)acute stroke subjects that had not used these orthoses before. PMID- 27390154 TI - Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour. AB - The five-subunit WASH complex generates actin networks that participate in endocytic trafficking, migration and invasion in various cell types. Loss of one of the two subunits WASH or strumpellin in mice is lethal, but little is known about their role in mammals in vivo. We explored the role of strumpellin, which has previously been linked to hereditary spastic paraplegia, in the mouse melanocytic lineage. Strumpellin knockout in melanocytes revealed abnormal endocytic vesicle morphology but no impairment of migration in vitro or in vivo and no change in coat colour. Unexpectedly, WASH and filamentous actin could still localize to vesicles in the absence of strumpellin, although the shape and size of vesicles was altered. Blue native PAGE revealed the presence of two distinct WASH complexes, even in strumpellin knockout cells, revealing that the WASH complex can assemble and localize to endocytic compartments in cells in the absence of strumpellin. PMID- 27390155 TI - How Sensitive Is the Upper Gastrointestinal Tract to 90Y Radioembolization? A Histologic and Dosimetric Analysis in a Porcine Model. AB - : In 90Y radioembolization, nontarget embolization to the stomach or small bowel can result in gastrointestinal injury, a rare but difficult to manage clinical complication. However, dosimetric thresholds for toxicity to these tissues from radioembolization have never been evaluated in a controlled setting. We performed an analysis of the effect of 90Y radioembolization in a porcine model at different absorbed-dose endpoints. METHODS: Six female pigs underwent transfemoral angiography and infusion of 90Y-resin microspheres into arteries supplying part of the gastric wall. Esophagogastroduodenoscopy was performed after 4 wk to assess interim gastrointestinal health. Animals were monitored for side effects for 9 wk after 90Y infusion, after which they were euthanized and their upper gastrointestinal tracts were excised for analysis. Histologic sections were used to map microsphere location, and a microdosimetric evaluation was performed to determine the absorbed-dose profile within the gastrointestinal wall. RESULTS: 90Y radioembolization dosages from 46.3 to 105.1 MBq were infused, resulting in average absorbed doses of between 35.5 and 91.9 Gy to the gastric wall. No animal exhibited any signs of pain or gastrointestinal distress through the duration of the study. Excised tissue showed 1-2 small (<3.0 cm2) healed or healing superficial gastric lesions in 5 of 6 animals. Histologic analysis demonstrated that lesion location was superficial to areas of abnormally high microsphere deposition. An analysis of microsphere deposition patterns within the gastrointestinal wall indicated a high preference for submucosal deposition. Dosimetric evaluation at the luminal mucosa performed on the basis of microscopic microsphere distribution confirmed that 90Y dosimetry techniques conventionally used in hepatic dosimetry provide a first-order estimate of absorbed dose. CONCLUSION: The upper gastrointestinal tract may be less sensitive to 90Y radioembolization than previously thought. Lack of charged-particle equilibrium at the luminal mucosa may contribute to decreased toxicity of 90Y radioembolization compared with external-beam radiation therapy in gastrointestinal tissue. Clinical examples of injury from 90Y nontarget embolization have likely resulted from relatively large 90Y activities being deposited in small tissue volumes, resulting in absorbed doses in excess of 100 Gy. PMID- 27390156 TI - Quantification of Task-Specific Glucose Metabolism with Constant Infusion of 18F FDG. AB - : The investigation of cerebral metabolic rate of glucose (CMRGlu) at baseline and during specific tasks previously required separate scans with the drawback of high intrasubject variability. We aimed to validate a novel approach to assessing baseline glucose metabolism and task-specific changes in a single measurement with a constant infusion of 18F-FDG. METHODS: Fifteen healthy subjects underwent two PET measurements with arterial blood sampling. As a reference, baseline CMRGlu was quantified from a 60-min scan after 18F-FDG bolus application using the Patlak plot (eyes closed). For the other scan, a constant radioligand infusion was applied for 95 min, during which the subjects opened their eyes at 10-20 min and 60-70 min and tapped their right thumb to their fingers at 35-45 min and 85-95 min. The constant-infusion scan was quantified in two steps. First, the general linear model was used to fit regional time-activity curves with regressors for baseline metabolism, task-specific changes for the eyes-open and finger-tapping conditions, and movement parameters. Second, the Patlak plot was used for quantification of CMRGlu. Multiplication of the baseline regressor by beta-values from the general linear model yielded regionally specific time activity curves for baseline metabolism. Further, task-specific changes in metabolism are directly proportional to changes in the slope of the time-activity curve and hence to changes in CMRGlu. RESULTS: Baseline CMRGlu from the constant infusion scan matched that from the bolus application (test-retest variability, 1.1% +/- 24.7%), which was not the case for a previously suggested approach (variability, -39.9% +/- 25.2%, P < 0.001). Task-specific CMRGlu increased in the primary visual and motor cortices for eyes open and finger tapping, respectively (P < 0.05, familywise error-corrected), with absolute changes of up to 2.1 MUmol/100 g/min and 6.3% relative to baseline. For eyes open, a decreased CMRGlu was observed in default-mode regions (P < 0.05, familywise error-corrected). CMRGlu quantified with venous blood samples (n = 6) showed excellent agreement with results obtained from arterial samples (r > 0.99). CONCLUSION: Baseline glucose metabolism and task-specific changes can be quantified in a single measurement with constant infusion of 18F-FDG and venous blood sampling. The high sensitivity and regional specificity of the approach offer novel possibilities for functional and multimodal brain imaging. PMID- 27390157 TI - PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model. AB - : The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. METHODS: New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0- to 60-min dynamic whole body PET/MR examination was performed after injection of approximately 111 MBq of 64Cu-ATSM. After 24 h, a 0- to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 alpha subunit [HIF-1alpha]). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. RESULTS: Elevated uptake of 64Cu-ATSM was found in the rabbits' IF compared with the SF. 64Cu-ATSM imaging demonstrated IF to-SF SUVmean ratios (+/-SD) of 1.75 +/- 0.21 and 2.30 +/- 0.26 at 4 and 8 wk after injury, respectively. 18F-FDG imaging demonstrated IF-to-SF SUVmean ratios of 1.84 +/- 0.12 at 8 wk after injury. IF-to-BM SUVmean ratios were significantly higher (P < 0.001) than SF-to-BM SUVmean ratios both 4 and 8 wk after injury for 64Cu-ATSM and 8 wk after injury for 18F-FDG (P < 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1alpha. CONCLUSION: The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that 64Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects. PMID- 27390159 TI - 11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis. AB - : Myocarditis represents a major cause of dilated cardiomyopathy and sudden cardiac death in younger adults. Currently, definitive diagnosis of myocarditis requires endomyocardial biopsy, which is highly invasive and has the drawback of variable sensitivity due to inherent sampling error. Therefore, reliable noninvasive methods to detect and monitor cardiac inflammation are clinically relevant. In this study, we explored the potential of radiolabeled methionine to assess myocardial inflammatory activity in a rat model of experimental autoimmune myocarditis (EAM). METHODS: Autoimmune myocarditis was induced by immunizing Lewis rats twice with porcine cardiac myosin and Freund complete adjuvant. Control animals were treated with adjuvant alone. Dual-tracer autoradiography was performed to assess 14C-methionine uptake and to compare the distributions of 14C methionine versus 18F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18F-FDG PET was also conducted to compare the in vivo uptake of 11C-methionine and 18F-FDG. RESULTS: Multiple focal cardiac inflammatory lesions were histologically identified in myosin-immunized rats, whereas no cardiac lesions were observed in the controls. Autoradiographic images clearly showed a high density accumulation of 14C-methionine in inflammatory lesions of EAM rats, whereas no significant uptake was observed in the control animals. 14C-methionine uptake was significantly higher in inflammatory lesions than in remote noninflammatory areas and control rat hearts. The distribution of 14C-methionine correlated well with that of 18F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18F-FDG than for 14C-methionine (3.45 +/- 0.68 vs. 2.07 +/- 0.21, respectively; P < 0.05). In the PET imaging study, the regional 11C-methionine uptake (percentage injected dose per cubic centimeter) observed in EAM rats was significantly higher than the values obtained for control animals (0.64 +/- 0.09 vs. 0.28 +/- 0.02, respectively; P < 0.001). A good positive correlation between 11C-methionine and 18F-FDG uptake was found. CONCLUSION: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis. PMID- 27390158 TI - 225Ac-PSMA-617 for PSMA-Targeted alpha-Radiation Therapy of Metastatic Castration Resistant Prostate Cancer. AB - : Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an alpha radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225Ac-PSMA-617 therapy. METHODS: 68Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68Ga-PSMA-11 PET/CT. RESULTS: Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect. CONCLUSION: Targeted alpha-therapy with 225Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients. PMID- 27390160 TI - Radionuclide Imaging of Musculoskeletal Infection: A Review. AB - There are numerous imaging tests for diagnosing musculoskeletal infection. Radiographs are routinely performed, because even when not diagnostic, they provide an anatomic overview of the region of interest that could influence subsequent procedure selection and interpretation. MRI is sensitive and provides superb anatomic detail. Bone scintigraphy accurately diagnoses osteomyelitis in bones not affected by underlying conditions. (67)Ga is used primarily for spondylodiskitis. Although in vitro labeled leukocyte imaging is the radionuclide test of choice for complicating osteomyelitis such as diabetic pedal osteomyelitis and prosthetic joint infection, it is not useful for spondylodiskitis. Antigranulocyte antibodies and antibody fragments have limitations and are not widely available. (111)In-biotin is useful for spondylodiskitis. Radiolabeled synthetic fragments of the antimicrobial peptide ubiquicidin are promising infection-specific agents. (18)F-FDG is the radiopharmaceutical of choice for spondylodiskitis. Its role in diabetic pedal osteomyelitis and prosthetic joint infection is not established. Preliminary data suggest (68)Ga may be useful in musculoskeletal infection. (124)I-fialuridine initially showed promise as an infection-specific radiopharmaceutical, but subsequent investigations were disappointing. The development of PET/CT and SPECT/CT imaging systems, which combine anatomic and functional imaging, has revolutionized diagnostic imaging. These hybrid systems are redefining the diagnostic workup of patients with suspected or known infection and inflammation by improving diagnostic accuracy and influencing patient management. PMID- 27390162 TI - Associations Between Fat Mass and Multisite Pain: A Five-Year Longitudinal Study. AB - OBJECTIVE: Pain is common in older adults and typically involves multiple sites. Obesity is an important risk factor in the pathogenesis of pain and multisite pain (MSP). This study aimed to examine longitudinal associations between fat mass and MSP, and to explore the potential mechanisms of any associations. METHODS: Data from a longitudinal population-based study of older adults (n = 1,099) were utilized with measurements at baseline and after 2.6 and 5.1 years. At each time point, presence/absence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire. Fat mass was assessed by dual x-ray absorptiometry, and height and weight were measured. RESULTS: Participants were of mean age 63 years, mean body mass index (BMI) 27.9 kg/m2 , and 51% women. Participants reporting greater number of painful sites had greater fat mass, fat mass index (FMI), and BMI both cross-sectionally and longitudinally. In multivariable analyses, fat mass was associated with MSP (odds ratio [OR] 1.06 per SD; 95% confidence interval [95% CI] 1.02-1.10) and pain at the hands, knees, hips, and feet (OR 1.29-1.99 per SD, P < 0.05 for all). Results were similar for FMI and BMI, although the latter was also associated with back pain (OR 1.25 per SD, 95% CI 1.02-1.54). CONCLUSION: Fat mass, FMI, and BMI are associated with MSP and pain at all lower-extremity sites and hand pain, independent of sociodemographic, physical activity, and psychological factors. This suggests that both loading and systemic inflammatory factors may have an important role in the pathogenesis of fat-related MSP. PMID- 27390161 TI - Selective Imaging of VEGFR-1 and VEGFR-2 Using 89Zr-Labeled Single-Chain VEGF Mutants. AB - : Vascular endothelial growth factor-A (VEGF-A) acts via 2 vascular endothelial growth factor receptors, VEGFR-1 and VEGFR-2, that play important and distinct roles in tumor biology. We reasoned that selective imaging of these receptors could provide unique information for diagnostics and for monitoring and optimizing responses to anticancer therapy, including antiangiogenic therapy. Herein, we report the development of 2 first-in-class 89Zr-labeled PET tracers that enable the selective imaging of VEGFR-1 and VEGFR-2. METHODS: Functionally active mutants of scVEGF (an engineered single-chain version of pan-receptor VEGF A with an N-terminal cysteine-containing tag for site-specific conjugation), named scVR1 and scVR2 with enhanced affinity to, respectively, VEGFR-1 and VEGFR 2, were constructed. Parental scVEGF and its receptor-specific mutants were site specifically derivatized with the 89Zr chelator desferroxamine B via a 3.4-kDa PEG linker. 89Zr labeling of the desferroxamine B conjugates furnished scV/Zr, scVR1/Zr, and scVR2/Zr tracers with high radiochemical yield (>87%), high specific activity (>=9.8 MBq/nmol), and purity (>99%). Tracers were tested in an orthotopic breast cancer model using 4T1luc-bearing syngeneic BALB/c mice. For testing tracer specificity, tracers were coinjected with an excess of cold proteins of the same or opposite receptor specificity or pan-receptor scVEGF. PET imaging, biodistribution, and dosimetry studies in mice, as well as immunohistochemical analysis of harvested tumors, were performed. RESULTS: All tracers rapidly accumulated in orthotopic 4T1luc tumors, allowing for the successful PET imaging of the tumors as early as 2 h after injection. Blocking experiments with an excess of pan-receptor or receptor-specific cold proteins indicated that more than 80% of tracer tumor uptake is VEGFR-mediated, whereas uptake in all major organs is not affected by blocking within the margin of error. Critically, blocking experiments indicated that VEGFR-mediated tumor uptake of scVR1/Zr and scVR2/Zr was mediated exclusively by the corresponding receptor, VEGFR-1 or VEGFR-2, respectively. In contrast, uptake of pan-receptor scV/Zr was mediated by both VEGFR-1 and VEGFR-2 at an approximately 2:1 ratio. CONCLUSION: First-in-class selective PET tracers for imaging VEGFR-1 and VEGFR-2 were constructed and successfully validated in an orthotopic murine tumor model. PMID- 27390163 TI - The Moral Frameworks and Foundations of Contesting Orientations. AB - According to contesting theory (Shields & Bredemeier, 2011), people conceptualize competition either through a metaphor of partnership or war. These two alternate metaphors suggest differing sociomoral relationships among the participants. In the current study of intercollegiate athletes (n = 610), we investigated the two approaches to contesting in relation to formalist and consequentialist moral frameworks (Brady & Wheeler, 1996) and individualizing and binding moral foundations (Haidt, 2001). Correlational analysis indicated that the partnership approach correlated significantly with all four moral dimensions, while the war approach correlated with formalist and consequentialist frameworks and binding foundations (i.e., appeals to in-group loyalty, authority, and purity). Multiple regressions demonstrated that the best predictors of a partnership approach were formalist thinking and endorsement of individualizing moral foundations (i.e., appeal to fairness and welfare). Among our primary variables, the best predictors of a war orientation were consequentialist thinking and endorsement of binding foundations. PMID- 27390165 TI - Editorial. PMID- 27390166 TI - Zika virus infection and once again the risk from other neglected diseases. AB - Since the first cases of Zika were identified and reported in Brazil, the magnitude and consequences of the outbreak in the Americas have increased tremendously, leading the World Health Organization to consider Zika and its link with clusters of microcephaly a Public Health Emergency of International Concern. Only a previous large outbreak in French Polynesia was known and no neurological anomalies have been reported. Differences in African and Asian lineage and differences in genetic evolution of the Zika virus may possibly provide an explanation for the development of the recent outbreaks and their variable presentation. However, the similar clinical presentation between Zika and other diseases like Dengue and Chikungunya can support that Zika has been circulating and spreading inadvertently. This hypothesis gains strength when rates of laboratory confirmation diagnosis for Dengue are observed in Brazil and Colombia, two of the most affected countries by Zika virus (ZIKV) infection.The lack of attention and resources on neglected diseases supposes a huge risk that new lethal pathogens camouflage themselves to spread into large areas and populations. PMID- 27390164 TI - Is the Sequence of SuperAlarm Triggers More Predictive Than Sequence of the Currently Utilized Patient Monitor Alarms? AB - OBJECTIVE: Our previous studies have shown that "code blue" events can be predicted by SuperAlarm patterns that are multivariate combinations of monitor alarms and laboratory test results cooccurring frequently preceding the events but rarely among control patients. Deploying these patterns to the monitor data streams can generate SuperAlarm sequences. The objective of this study is to test the hypothesis that SuperAlarm sequences may contain more predictive sequential patterns than monitor alarms sequences. METHODS: Monitor alarms and laboratory test results are extracted from a total of 254 adult coded and 2213 control patients. The training dataset is composed of subsequences that are sampled from complete sequences and then further represented as fixed-dimensional vectors by the term frequency inverse document frequency method. The information gain technique and weighted support vector machine are adopted to select the most relevant features and train a classifier to differentiate sequences between coded patients and control patients. Performances are assessed based on an independent dataset using three metrics: sensitivity of lead time (Sen L @T), alarm frequency reduction rate (AFRR), and work-up to detection ratio (WDR). RESULTS: The performance of 12-h-long sequences of SuperAlarm can yield a Sen L@2 of 93.33%, an AFRR of 87.28%, and a WDR of 3.01. At an AFRR = 87.28%, Sen L@2 for raw alarm sequences and discretized alarm sequences are 73.33% and 70.19%, respectively. At a WDR = 3.01, Sen L@2 are 49.88% and 43.33%. CONCLUSION AND SIGNIFICANCE: The results demonstrate that SuperAlarm sequences indeed outperform monitor alarm sequences and suggest that one can focus on sequential patterns from SuperAlarm sequences to develop more precise patient monitoring solutions. PMID- 27390167 TI - Variations in Radiographic Procedure Use for Medicare Patients With Rheumatoid Arthritis. AB - OBJECTIVE: In 2013, the American College of Rheumatology published its Choosing Wisely list, which identified 2 radiographic procedures (peripheral joint magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA] scans) that were at risk for overuse. METHODS: We performed a retrospective cross-sectional cohort study to measure the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans in a national cohort of Medicare patients with rheumatoid arthritis (RA) during 2008-2009, before the start of the Choosing Wisely campaign. Diagnoses were identified via International Classification of Diseases, Ninth Revision, codes; utilization was calculated using Current Procedural Terminology codes. Utilization was analyzed at the individual level and at the regional level (by hospital referral region [HRR]). RESULTS: There were 8,051 patients with RA who were included: 81% were women, and the mean age was 76 years. Over a 2-year period, the mean number of peripheral joint MRIs per beneficiary was 0.3 (median 0 [range 0-50]), peripheral joint radiographs per beneficiary was 2.6 (median 1 [range 0-33]), and DXA scans per beneficiary was 0.7 (median 0 [range 0-11]). Only 6.8% of patients received >1 peripheral joint MRI, and 6% of HRRs had a mean number of peripheral joint MRIs >1. CONCLUSION: There is variation in the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans among Medicare patients with RA, although only a small number of HRRs have consistently high utilization. Although we cannot judge the appropriateness of each procedure, variation in use across regions signals the need for investigations to examine potential overutilization. PMID- 27390168 TI - Post Hoc Analysis of the Phase II/III APRIL-SLE Study: Association Between Response to Atacicept and Serum Biomarkers Including BLyS and APRIL. AB - OBJECTIVE: To assess the relationship between treatment response, baseline biomarker levels, and atacicept exposure in patients with systemic lupus erythematosus (SLE) in the phase II/III APRIL-SLE study. METHODS: We performed a post hoc analysis of patients who received placebo, atacicept 75 mg, or atacicept 150 mg in a randomized, controlled, 52-week trial. Serum levels of BlyS and APRIL were measured at baseline, and serum levels of Ig and the numbers of naive B cells and plasma cells were measured at baseline and during treatment. Atacicept exposure was determined by assessment of the serum trough concentrations throughout the 52-week trial period. Associations between these parameters, treatment response (reduction in British Isles Lupus Assessment Group A or B flare), and infection rates were explored. RESULTS: Recurrent high baseline levels of both BLyS (>=1.6 ng/ml) and APRIL (>=2.2 ng/ml) correlated with a greater treatment response (flare rate 75.7% with placebo, and 50.0% and 32.0% with atacicept 75 mg and atacicept 150 mg, respectively) compared with lower baseline levels of both. Increased atacicept exposure correlated with reduced flare rates (60.5% with placebo; 63.4%, 61.0%, 48.8%, and 29.3% in the 4 quartiles, from lowest to highest atacicept exposure). Greater pharmacodynamic responses (reduced Ig levels and naive B cell and plasma cell numbers) were associated with greater reductions in the flare rate. Infection rates were similar regardless of biomarker levels at baseline or at the time of atacicept exposure. CONCLUSION: These post hoc analyses demonstrate a dose-response relationship between atacicept concentrations, reduced Ig levels, and reduced flare rates and suggest that baseline biomarkers such as elevated serum levels of BLyS and APRIL may help to identify the patients who are most likely to benefit from atacicept treatment. PMID- 27390169 TI - Tuberculosis, Brucellosis and Leucosis in Cattle: A Cost Description of Eradication Programmes in the Region of Lazio, Italy. AB - The eradication of tuberculosis, brucellosis and leucosis in cattle has not yet been achieved in the entire Italian territory. The region of Lazio, Central Italy, represents an interesting case study to evaluate the evolution of costs for these eradication programmes, as in some provinces the eradication has been officially achieved, in some others the prevalence has been close to zero for years, and in still others disease outbreaks have been continuously reported. The objectives of this study were i) to describe the costs for the eradication programmes for tuberculosis, brucellosis and leucosis in cattle carried out in Lazio between 2007 and 2011, ii) to calculate the ratio between the financial contribution of the European Union (EU) for the eradication programmes and the estimated total costs and iii) to estimate the potential savings that can be made when a province gains the certification of freedom from disease. For the i) and ii) objectives, data were collected from official sources and a costing procedure was applied from the perspective of the Regional Health Service. For the iii) objective, a Bayesian AR(1) regression was used to evaluate the average percentage reduction in costs for a province that gained the certification. The total cost for the eradication programmes adjusted for inflation to 1 January 2016 was estimated at 18 919 797 euro (5th and 95th percentiles of the distribution: 18 325 050-19 552 080 euro). When a province gained the certification of freedom from disease, costs decreased on average by (median of the posterior distribution) 47.5%, 54.5% and 54.9% for the eradication programmes of tuberculosis, brucellosis and leucosis, respectively. Information on possible savings from the reduction of control costs can help policy makers operating under budget constraints to justify the use of additional resources for the final phase of eradication. PMID- 27390170 TI - Peter Alan Trott. PMID- 27390171 TI - Analysis of monosomy-3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients. AB - Monosomy-3 in primary uveal melanoma (UM) is associated with a high risk of metastasis and mortality. Although circulating melanoma cells (CMC) can be found in most UM patients, only approximately 50% of the patients develop metastases. We utilized a novel immuno-FISH assay to detect chromosome-3 in intact CMC isolated by dual immunomagnetic enrichment. Circulating melanoma cells were detected in 91% of the patients (n = 44) with primary non-metastatic UM, of which 58% were positive for monosomy-3. The monosomy-3 status of CMC corresponded to the monosomy-3 status of the primary tumor in 10 of the 11 patients where this could be tested. Monosomy-3 in the CMC was associated with an advanced tumor stage (P = 0.046) and was detected in all four patients who developed metastasis within the follow-up period of 4 yr. This non-invasive technique may enable the identification of UM patients at risk for metastasis particularly when a primary tumor specimen is unavailable. PMID- 27390172 TI - The family accompaniment of persons with dementia seen through the lens of the capability approach. AB - Using the capability approach initially developed by A Sen as a theoretical framework, this paper analyses both what people with dementia and their families do in response to difficulties in their daily life brought about by the disease, and the reasons they give for acting as they do. Individual and collective interviews and ethnographic observations with 15 persons with dementia and one or more of their family members were conducted. Follow-up interviews were possible for nine families. Results highlight a great diversity in ways of doing things and in accompaniment by family members. Daily adjustments are often hidden or minimized, at least at the onset of the dementia. Later, they become more frequent, repetitive and indispensable but remain influenced by the social and gender roles that existed prior to the illness. The inventiveness of families, in a context marked by various kinds of constraints, is primarily motivated by their desire to maintain the apparently intact abilities of the person with dementia but especially to preserve forms of liberty and what counted for the person, what that person valued before the disease. There are some ways of living with dementia, even when accompanied, which may long remain preferable to others, which better answer to the past and present aspirations of persons with dementia and the purposes of the accompanying persons. It is thus essential that health professionals, as well as society in general, recognize and address this issue. PMID- 27390174 TI - Designing Switchable Phononic Crystal-Based Acoustic Demultiplexer. AB - We present the design procedure for switchable acoustic demultiplexers based on a fluid-fluid phononic crystal (PnC) platform. It consists of a T-shaped PnC waveguide coupled to two output waveguide ports through two dissimilar point defect cavities. The PnC platform consists of a periodic array of infinitely long rods of water (inclusions) embedded in mercury background. The waveguides are made by the removal of a row or a column of inclusions from the PnC, while the fluid in one of the two dissimilar cavities is methyl nonafluorobutyl ether (MNE) and in the other is ethyl nonafluorobutyl ether (ENE). The difference in the sound velocity in MNE and ENE provides an adequate difference in the dissimilar cavities resonant modes, required for the demultiplexing functionality of the designed structure. The different dependences of the sound velocities in these two fluids on temperature have also enabled the switching of the multiplexed channel, simply by appropriately changing the cavities temperature. PMID- 27390175 TI - Automatic Reference Color Selection for Adaptive Mathematical Morphology and Application in Image Segmentation. AB - This paper proposes a novel automatic reference color selection (ARCS) scheme for the adaptive mathematical morphology (MM) method, and is specifically designed for color image segmentation applications. Because of the main advantages of being intuitive and simple, in the past decade, it has contributed to the growing popularity of binary and gray-scale MM processing. However, the MM process typically neglects the details of reference color determination. Applying other ordering methods, which select only black as the reference color for sorting pixels, result in the problem in which the scope of the distance measurement is not optimal. The proposed ARCS scheme is used for determining the ideal reference color for MM and for color image segmentation application. In addition, we use both 1D histogram-based modeling scheme binning from 3D color spaces, such as red green-blue and hue-saturation-intensity, and 2D color models, such as (H, S), (Cb, Cr), and (I, By). According to the results of the quartile analysis, the threshold determination reacts with less sensitivity to the context variations of the images tested. The experiments focused on color-based image segmentation using the proposed ARCS scheme for color MM processing through a bottom-up scenario. To evaluate the system, four quantitative indices were utilized for an ARCS comparison using advanced segmentation methods in the experiments. The cross validation with different system parameters and a comparison of the morphological gradient operation with different color models are also presented. PMID- 27390173 TI - Two new competing pathways establish the threshold for cyclin-B-Cdk1 activation at the meiotic G2/M transition. AB - Extracellular ligands control biological phenomena. Cells distinguish physiological stimuli from weak noise stimuli by establishing a ligand concentration threshold. Hormonal control of the meiotic G2/M transition in oocytes is essential for reproduction. However, the mechanism for threshold establishment is unclear. In starfish oocytes, maturation-inducing hormones activate the PI3K-Akt pathway through the Gbetagamma complex of heterotrimeric G proteins. Akt directly phosphorylates both Cdc25 phosphatase and Myt1 kinase, resulting in activation of cyclin-B-Cdk1, which then induces meiotic G2/M transition. Here, we show that cyclin-B-Cdk1 is partially activated after subthreshold hormonal stimuli, but this triggers negative feedback, resulting in dephosphorylation of Akt sites on Cdc25 and Myt1, thereby canceling the signal. We also identified phosphatase activity towards Akt substrates that exists independent of stimuli. In contrast to these negative regulatory activities, an atypical Gbetagamma-dependent pathway enhances PI3K-Akt-dependent phosphorylation. Based on these findings, we propose a model for threshold establishment in which hormonal dose-dependent competition between these new pathways establishes a threshold; the atypical Gbetagamma-pathway becomes predominant over Cdk-dependent negative feedback when the stimulus exceeds this threshold. Our findings provide a regulatory connection between cell cycle and signal transduction machineries. PMID- 27390176 TI - Registration and Modeling From Spaced and Misaligned Image Volumes. AB - We address the problem of object modeling from 3D and 3D+T data made up of images, which contain different parts of an object of interest, are separated by large spaces, and are misaligned with respect to each other. These images have only a limited number of intersections, hence making their registration particularly challenging. Furthermore, such data may result from various medical imaging modalities and can, therefore, present very diverse spatial configurations. Previous methods perform registration and object modeling (segmentation and interpolation) sequentially. However, sequential registration is ill-suited for the case of images with few intersections. We propose a new methodology, which, regardless of the spatial configuration of the data, performs the three stages of registration, segmentation, and shape interpolation from spaced and misaligned images simultaneously. We integrate these three processes in a level set framework, in order to benefit from their synergistic interactions. We also propose a new registration method that exploits segmentation information rather than pixel intensities, and that accounts for the global shape of the object of interest, for increased robustness and accuracy. The accuracy of registration is compared against traditional mutual information based methods, and the total modeling framework is assessed against traditional sequential processing and validated on artificial, CT, and MRI data. PMID- 27390177 TI - The flexibility of a homeodomain transcription factor heterodimer and its allosteric regulation by DNA binding. AB - Transcription factors are known to modify the DNA that they bind. However, DNA can also serve as an allosteric ligand whose binding modifies the conformation of transcriptional regulators. Here, we describe how heterodimer PBX1:PREP1, formed by proteins playing major roles in embryonic development and tumorigenesis, undergoes an allosteric transition upon DNA binding. We demonstrate through a number of biochemical and biophysical methods that PBX1:PREP1 exhibits a structural change upon DNA binding. Small-angle X-ray scattering (SAXS), circular dichroism (CD), isothermal titration calorimetry (ITC), and limited proteolysis demonstrate a different shape, alpha-helical content, thermodynamic behavior, and solution environment of the holo-complex (with DNA) compared to the apo-complex (without DNA). Given that PBX1 as such does not have a defined DNA selectivity, structural changes upon DNA binding become major factors in the function of the PBX1:PREP1 complex. The observed changes are mapped at both the amino- and carboxy-terminal regions of the two proteins thereby providing important insights to determine how PBX1:PREP1 dimer functions. DATABASE: Small-angle scattering data are available in SASBDB under accession numbers SASDAP7, SASDAQ7, and SASDAR7. PMID- 27390178 TI - ORM Elevation in Response to Cognitive Impairment Is an Accompanying Phenomenon. PMID- 27390179 TI - Empirical Movement Models for Brain Computer Interfaces. AB - For brain-computer interfaces (BCIs) which provide the user continuous position control, there is little standardization of performance metrics or evaluative tasks. One candidate metric is Fitts's law, which has been used to describe aimed movements across a range of computer interfaces, and has recently been applied to BCI tasks. Reviewing selected studies, we identify two basic problems with Fitts's law: its predictive performance is fragile, and the estimation of 'information transfer rate' from the model is unsupported. Our main contribution is the adaptation and validation of an alternative model to Fitts's law in the BCI context. We show that the Shannon-Welford model outperforms Fitts's law, showing robust predictive power when target distance and width have disproportionate effects on difficulty. Building on a prior study of the Shannon Welford model, we show that identified model parameters offer a novel approach to quantitatively assess the role of control-display gain in speed/accuracy performance tradeoffs during brain control. PMID- 27390180 TI - A Model for Single Neuron Activity With Refractory Effects and Spike Rate Estimation Techniques. AB - The use of random point processes as models for neural spike trains allows the derivation of powerful statistical estimation techniques for time varying firing rates. Frequently, however, such estimators are based on the assumption that spike sequences follow a Poisson point process. Because of the bio-physical properties of neuronal action potentials, spike trains are affected by the refractory phenomenon that induces history dependency, and hence contradicts the Poisson assumption. In this work we present a neural spiking model, and a Maximum Likelihood (ML) estimation framework for time varying firing rates, that account for history dependencies in spike trains. Our framework is based on an exponential of polynomial model for the excitation function (stimulus), that generates a self exciting point process representing spike trains with absolute as well as relative refractory effects. Using this framework we employ techniques based on non-convex optimization and model order selection to derive ML estimators for neuronal firing rates. Results on simulated data with a refractory period show an improvement in accuracy when our estimation technique, that accounts for the complete refractory phenomenon, is used. Employing this estimation method for measured neuronal data shows an improvement in goodness of fit over estimators that do not account for the refractory effect, and also over other commonly used techniques. PMID- 27390181 TI - Functional Assessment of a Myoelectric Postural Controller and Multi-Functional Prosthetic Hand by Persons With Trans-Radial Limb Loss. AB - The functional assessment of myoelectric control algorithms by persons with amputation promotes the overarching goal of the field of prosthetic limb design: to replace what was lost. However, many studies use experimental paradigms with virtual interfaces and able-bodied subjects that do not capture the challenges of a clinical implementation with an amputee population. A myoelectric control system must be robust to variable physiology, loading effects of the prosthesis on the limb, and limb position effects during dynamic tasks. Here persons with transradial limb loss performed activities of daily living using a postural controller and multi-functional prosthetic hand in order to verify that the postural controller was robust to these clinical challenges. The Southampton Hand Assessment Procedure was performed by persons with limb loss and able-bodied subjects. The results indicate that persons with limb loss and able-limbed subjects achieved the same performance and therefore that the clinical challenges were overcome. Persons with limb loss achieved 55% of physiological hand function on average. Also, the postural controller is compared to other state of the art myoelectric controllers and prosthetic hands previously tested. This work confirms that the postural controller is potentially a clinically-viable method to control myoelectric multi-functional prosthetic hands. PMID- 27390182 TI - Vibrotactile Sensitivity in Active Touch: Effect of Pressing Force. AB - An experiment was conducted to study the effects of force produced by active touch on vibrotactile perceptual thresholds. The task consisted in pressing the fingertip against a flat rigid surface that provided either sinusoidal or broadband vibration. Three force levels were considered, ranging from light touch to hard press. Finger contact areas were measured during the experiment, showing positive correlation with the respective applied forces. Significant effects on thresholds were found for vibration type and force level. Moreover, possibly due to the concurrent effect of large (unconstrained) finger contact areas, active pressing forces, and long duration stimuli, the measured perceptual thresholds are considerably lower than what previously reported in the literature. PMID- 27390183 TI - Michael Stephen Arnold Townsend. PMID- 27390184 TI - Association Between Pain at Sites Outside the Knee and Knee Cartilage Volume Loss in Elderly People Without Knee Osteoarthritis: A Prospective Study. AB - OBJECTIVE: Pain is common in the elderly. Knee pain may predict knee cartilage loss, but whether generalized pain is associated with knee cartilage loss is unclear. This study, therefore, aimed to determine whether pain at multiple sites predicts knee cartilage volume loss among community-dwelling older adults, and, if so, to explore potential mechanisms. METHODS: Data from the prospective Tasmanian Older Adult Cohort study was utilized (n = 394, mean age 63 years, range 52-79 years). Experience of pain at multiple sites was assessed using a questionnaire at baseline. T1-weighted fat-saturated magnetic resonance imaging of the right knee was performed to assess the cartilage volume at baseline and after 2.6 years. Linear regression modeling was used with adjustment for potential confounders. RESULTS: The median number of painful sites was 3 (range 0 7). There was a dose-response relationship between the number of painful sites and knee cartilage volume loss in the lateral and total tibiofemoral compartments (lateral beta = -0.28% per annum; total beta = -0.25% per annum, both P for trend < 0.05), but not in the medial compartment. These associations were stronger in participants without radiographic knee osteoarthritis (OA) (P < 0.05) and independent of age, sex, body mass index, physical activity, pain medication, and knee structural abnormalities. CONCLUSION: The number of painful sites independently predicts knee cartilage volume loss, especially in people without knee OA, suggesting that widespread pain may be an early marker of more rapid knee cartilage loss in those without radiographic knee OA. The underlying mechanism is unclear, but it is independent of anthropometrics, physical activity, and knee structural abnormalities. PMID- 27390185 TI - Can You Have Your Vigorous Exercise and Enjoy It Too? Ramping Intensity Down Increases Postexercise, Remembered, and Forecasted Pleasure. AB - There is a paucity of methods for improving the affective experience of exercise. We tested a novel method based on discoveries about the relation between exercise intensity and pleasure, and lessons from behavioral economics. We examined the effect of reversing the slope of pleasure during exercise from negative to positive on pleasure and enjoyment, remembered pleasure, and forecasted pleasure. Forty-six adults were randomly assigned to a 15-min bout of recumbent cycling of either increasing intensity (0-120% of watts corresponding to the ventilatory threshold) or decreasing intensity (120-0%). Ramping intensity down, thereby eliciting a positive slope of pleasure during exercise, improved postexercise pleasure and enjoyment, remembered pleasure, and forecasted pleasure. The slope of pleasure accounted for 35-46% of the variance in remembered and forecasted pleasure from 15 min to 7 days postexercise. Ramping intensity down makes it possible to combine exposure to vigorous and moderate intensities with a pleasant affective experience. PMID- 27390187 TI - Developing Electronic Health Record Algorithms That Accurately Identify Patients With Systemic Lupus Erythematosus. AB - OBJECTIVE: To study systemic lupus erythematosus (SLE) in the electronic health record (EHR), we must accurately identify patients with SLE. Our objective was to develop and validate novel EHR algorithms that use International Classification of Diseases, Ninth Revision (ICD-9), Clinical Modification codes, laboratory testing, and medications to identify SLE patients. METHODS: We used Vanderbilt's Synthetic Derivative, a de-identified version of the EHR, with 2.5 million subjects. We selected all individuals with at least 1 SLE ICD-9 code (710.0), yielding 5,959 individuals. To create a training set, 200 subjects were randomly selected for chart review. A subject was defined as a case if diagnosed with SLE by a rheumatologist, nephrologist, or dermatologist. Positive predictive values (PPVs) and sensitivity were calculated for combinations of code counts of the SLE ICD-9 code, a positive antinuclear antibody (ANA), ever use of medications, and a keyword of "lupus" in the problem list. The algorithms with the highest PPV were each internally validated using a random set of 100 individuals from the remaining 5,759 subjects. RESULTS: The algorithm with the highest PPV at 95% in the training set and 91% in the validation set was 3 or more counts of the SLE ICD-9 code, ANA positive (>=1:40), and ever use of both disease-modifying antirheumatic drugs and steroids, while excluding individuals with systemic sclerosis and dermatomyositis ICD-9 codes. CONCLUSION: We developed and validated the first EHR algorithm that incorporates laboratory values and medications with the SLE ICD-9 code to identify patients with SLE accurately. PMID- 27390189 TI - Improving Neural-Network Classifiers Using Nearest Neighbor Partitioning. AB - This paper presents a nearest neighbor partitioning method designed to improve the performance of a neural-network classifier. For neural-network classifiers, usually the number, positions, and labels of centroids are fixed in partition space before training. However, that approach limits the search for potential neural networks during optimization; the quality of a neural network classifier is based on how clear the decision boundaries are between classes. Although attempts have been made to generate floating centroids automatically, these methods still tend to generate sphere-like partitions and cannot produce flexible decision boundaries. We propose the use of nearest neighbor classification in conjunction with a neural-network classifier. Instead of being bound by sphere like boundaries (such as the case with centroid-based methods), the flexibility of nearest neighbors increases the chance of finding potential neural networks that have arbitrarily shaped boundaries in partition space. Experimental results demonstrate that the proposed method exhibits superior performance on accuracy and average f-measure. PMID- 27390188 TI - Tartrate-Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus. AB - OBJECTIVE: Mutations in the ACP5 gene, which encodes tartrate-resistant acid phosphatase (TRAP), cause the immuno-osseous disorder spondyloenchondrodysplasia, which includes as disease features systemic lupus erythematosus (SLE) and a type I interferon (IFN) signature. Our aims were to identify TRAP substrates, determine the consequences of TRAP deficiency in immune cells, and assess whether ACP5 mutations are enriched in sporadic cases of SLE. METHODS: Interaction between TRAP and its binding partners was tested by a yeast 2-hybrid screening, confocal microscopy, and immunoprecipitation/Western blotting. TRAP knockdown was performed using small interfering RNA. Phosphorylation of osteopontin (OPN) was analyzed by mass spectrometry. Nucleotide sequence analysis of ACP5 was performed by Sanger sequencing or next-generation sequencing. RESULTS: TRAP and OPN colocalized and interacted in human macrophages and plasmacytoid dendritic cells (PDCs). TRAP dephosphorylated 3 serine residues on specific OPN peptides. TRAP knockdown resulted in increased OPN phosphorylation and increased nuclear translocation of IRF7 and P65, with resultant heightened expression of IFN stimulated genes and IL6 and TNF following Toll-like receptor 9 stimulation. An excess of heterozygous ACP5 missense variants was observed in SLE compared to controls (P = 0.04), and transfection experiments revealed a significant reduction in TRAP activity in a number of variants. CONCLUSION: Our findings indicate that TRAP and OPN colocalize and that OPN is a substrate for TRAP in human immune cells. TRAP deficiency in PDCs leads to increased IFNalpha production, providing at least a partial explanation for how ACP5 mutations cause lupus in the context of spondyloenchondrodysplasia. Detection of ACP5 missense variants in a lupus cohort suggests that impaired TRAP functioning may increase susceptibility to sporadic lupus. PMID- 27390186 TI - Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models. AB - Dendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size, and morphology are some of the crucial factors determining how signals coming from individual synapses are integrated. Much remains to be understood about the characteristics of neuronal dendrites and dendritic spines in autism and related disorders. Although there have been many studies conducted using autism mouse models, few have been carried out using postmortem human tissue from patients. Available animal models of autism include those generated through genetic modifications and those non-genetic models of the disease. Here, we review how dendrite and spine morphology and number is affected in autism and related neurodevelopmental diseases, both in human, and genetic and non-genetic animal models of autism. Overall, data obtained from human and animal models point to a generalized reduction in the size and number, as well as an alteration of the morphology of dendrites; and an increase in spine densities with immature morphology, indicating a general spine immaturity state in autism. Additional human studies on dendrite and spine number and morphology in postmortem tissue are needed to understand the properties of these structures in the cerebral cortex of patients with autism. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017. PMID- 27390190 TI - Resolution of Singularities Introduced by Hierarchical Structure in Deep Neural Networks. AB - We present a theoretical analysis of singular points of artificial deep neural networks, resulting in providing deep neural network models having no critical points introduced by a hierarchical structure. It is considered that such deep neural network models have good nature for gradient-based optimization. First, we show that there exist a large number of critical points introduced by a hierarchical structure in deep neural networks as straight lines, depending on the number of hidden layers and the number of hidden neurons. Second, we derive a sufficient condition for deep neural networks having no critical points introduced by a hierarchical structure, which can be applied to general deep neural networks. It is also shown that the existence of critical points introduced by a hierarchical structure is determined by the rank and the regularity of weight matrices for a specific class of deep neural networks. Finally, two kinds of implementation methods of the sufficient conditions to have no critical points are provided. One is a learning algorithm that can avoid critical points introduced by the hierarchical structure during learning (called avoidant learning algorithm). The other is a neural network that does not have some critical points introduced by the hierarchical structure as an inherent property (called avoidant neural network). PMID- 27390193 TI - Analyzing and Identifying Teens' Stressful Periods and Stressor Events From a Microblog. AB - Increased health problems among adolescents caused by psychological stress have aroused worldwide attention. Long-standing stress without targeted assistance and guidance negatively impacts the healthy growth of adolescents, threatening the future development of our society. So far, research focused on detecting adolescent psychological stress revealed from each individual post on microblogs. However, beyond stressful moments, identifying teens' stressful periods and stressor events that trigger each stressful period is more desirable to understand the stress from appearance to essence. In this paper, we define the problem of identifying teens' stressful periods and stressor events from the open social media microblog. Starting from a case study of adolescents' posting behaviors during stressful school events, we build a Poisson-based probability model for the correlation between stressor events and stressful posting behaviors through a series of posts on Tencent Weibo (referred to as the microblog throughout the paper). With the model, we discover teens' maximal stressful periods and further extract details of possible stressor events that cause the stressful periods. We generalize and present the extracted stressor events in a hierarchy based on common stress dimensions and event types. Taking 122 scheduled stressful study-related events in a high school as the ground truth, we test the approach on 124 students' posts from January 1, 2012 to February 1, 2015 and obtain some promising experimental results: (stressful periods: recall 0.761, precision 0.737, and F1-measure 0.734) and (top-3 stressor events: recall 0.763, precision 0.756, and F1 -measure 0.759). The most prominent stressor events extracted are in the self-cognition domain, followed by the school life domain. This conforms to the adolescent psychological investigation result that problems in school life usually accompanied with teens' inner cognition problems. Compared with the state-of-the-art top-1 personal life event detection approach, our stressor event detection method is 13.72% higher in precision, 19.18% higher in recall, and 16.50% higher in F1-measure, demonstrating the effectiveness of our proposed framework. PMID- 27390195 TI - Escape Analysis on the Confinement-Escape Problem of a Defender Against an Evader Escaping From a Circular Region. AB - In this paper, we investigate some mathematical properties of the confinement escape problem of a defender and an evader with respect to a circular region, which was proposed in the author's previous work. Initially, the evader is located inside the circle, the defender patrols on the circle and tries to seal it to prevent the evader' escape; while the evader attempts to escape with avoidance of the defender. Here, we adopt the same control laws of the agents and consider particularly the successful-escape conditions which ensure a monotone increasing distance (MID) between the defender and the evader as the system evolves, for abbreviation, we call it the escape with the MID to the defender, or simply the MID escape. Then, we: 1) provide some sufficient conditions for the MID escape under different situations; 2) provide the corresponding upper-limit estimations of the escape time; and 3) discuss the characteristics of the analytical results. PMID- 27390196 TI - Rotational Invariant Dimensionality Reduction Algorithms. AB - A common intrinsic limitation of the traditional subspace learning methods is the sensitivity to the outliers and the image variations of the object since they use the norm as the metric. In this paper, a series of methods based on the -norm are proposed for linear dimensionality reduction. Since the -norm based objective function is robust to the image variations, the proposed algorithms can perform robust image feature extraction for classification. We use different ideas to design different algorithms and obtain a unified rotational invariant (RI) dimensionality reduction framework, which extends the well-known graph embedding algorithm framework to a more generalized form. We provide the comprehensive analyses to show the essential properties of the proposed algorithm framework. This paper indicates that the optimization problems have global optimal solutions when all the orthogonal projections of the data space are computed and used. Experimental results on popular image datasets indicate that the proposed RI dimensionality reduction algorithms can obtain competitive performance compared with the previous norm based subspace learning algorithms. PMID- 27390192 TI - Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat. AB - BACKGROUND: Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. METHODS: Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. RESULTS: Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1beta and TNF-alpha levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). CONCLUSION: SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. PMID- 27390194 TI - Vascular Evaluation of the Hand by Power Doppler Ultrasonography and New Predictive Markers of Ischemic Digital Ulcers in Systemic Sclerosis: Results of a Prospective Pilot Study. AB - OBJECTIVE: To evaluate the relevance of power Doppler ultrasonography (PDUS) as a predictive tool of 1-year digital ulcer (DU) occurrence in systemic sclerosis (SSc). METHODS: A total of 55 SSc patients and 19 controls underwent PDUS of both hands to evaluate the prevalence of ulnar artery occlusion (UAO) at baseline. Finger pulp blood flow (FPBF) of the third and fourth fingers was also assessed and considered as pathologic if a defect of the Doppler signal on a finger pulp was observed. All patients were clinically re-evaluated 6 and 12 months later and new ischemic DU occurrences in the meantime were retrospectively recorded. Patients were also asked to call if new DUs occurred between consultations. RESULTS: PDUS parameters were normal in all controls. The prevalence of UAO was 36.4% and was bilateral in 70% of the SSc cases. A total of 56.4% of SSc patients had a pathologic FPBF. UAO and pathologic FPBF were associated with a history of multiple DU episodes (odds ratio [OR] 8.98 [95% confidence interval (95% CI) 2.52 32.01], P < 0.001, and OR 4.69 [95% CI 1.30-16.93], P = 0.014, respectively) and the occurrence of new DUs during the followup in the univariable model (OR 8.73 [95% CI 2.00-38.16], P = 0.005, and OR 12.65 [95% CI 1.50-106.77], P = 0.005, respectively). The association of UAO and pathologic FPBF in the same patient was a predictive factor of new DUs in the multivariable analysis (P = 0.015). CONCLUSION: This study suggests that UAO and pathologic FPBF are associated with a history of multiple DUs and are predictors of new ischemic DUs. These parameters could be used as prognostic factors and considered in further studies evaluating DU treatment strategies. PMID- 27390197 TI - Stability of a Class of Multiagent Tracking Systems With Unstable Subsystems. AB - In this paper, we predeploy a large number of smart agents to monitor an area of interest. This area could be divided into many Voronoi cells by using the knowledge of Voronoi diagram and every Voronoi site agent is responsible for monitoring and tracking the target in its cell. Then, a cooperative relay tracking strategy is proposed such that during the tracking process, when a target enters a new Voronoi cell, this event triggers the switching of both tracking agents and communication topology. This is significantly different from the traditional switching topologies. In addition, during the tracking process, the topology and tracking agents switch, which may lead the tracking system to be stable or unstable. The system switches either among consecutive stable subsystems and consecutive unstable subsystems or between stable and unstable subsystems. The objective of this paper is to design a tracking strategy guaranteeing overall successful tracking despite the existence of unstable subsystems. We also address extended discussions on the case where the dynamics of agents are subject to disturbances and the disturbance attenuation level is achieved. Finally, the proposed tracking strategy is verified by a set of simulations. PMID- 27390198 TI - Discriminative Dictionary Learning With Two-Level Low Rank and Group Sparse Decomposition for Image Classification. AB - Discriminative dictionary learning (DDL) framework has been widely used in image classification which aims to learn some class-specific feature vectors as well as a representative dictionary according to a set of labeled training samples. However, interclass similarities and intraclass variances among input samples and learned features will generally weaken the representability of dictionary and the discrimination of feature vectors so as to degrade the classification performance. Therefore, how to explicitly represent them becomes an important issue. In this paper, we present a novel DDL framework with two-level low rank and group sparse decomposition model. In the first level, we learn a class-shared and several class-specific dictionaries, where a low rank and a group sparse regularization are, respectively, imposed on the corresponding feature matrices. In the second level, the class-specific feature matrix will be further decomposed into a low rank and a sparse matrix so that intraclass variances can be separated to concentrate the corresponding feature vectors. Extensive experimental results demonstrate the effectiveness of our model. Compared with the other state-of-the arts on several popular image databases, our model can achieve a competitive or better performance in terms of the classification accuracy. PMID- 27390199 TI - Trifocal Tensor-Based Adaptive Visual Trajectory Tracking Control of Mobile Robots. AB - In this paper, a trifocal tensor-based approach is proposed for the visual trajectory tracking task of a nonholonomic mobile robot equipped with a roughly installed monocular camera. The desired trajectory is expressed by a set of prerecorded images, and the robot is regulated to track the desired trajectory using visual feedback. Trifocal tensor is exploited to obtain the orientation and scaled position information used in the control system, and it works for general scenes owing to the generality of trifocal tensor. In the previous works, the start, current, and final images are required to share enough visual information to estimate the trifocal tensor. However, this requirement can be easily violated for perspective cameras with limited field of view. In this paper, key frame strategy is proposed to loosen this requirement, extending the workspace of the visual servo system. Considering the unknown depth and extrinsic parameters (installing position of the camera), an adaptive controller is developed based on Lyapunov methods. The proposed control strategy works for almost all practical circumstances, including both trajectory tracking and pose regulation tasks. Simulations are made based on the virtual experimentation platform (V-REP) to evaluate the effectiveness of the proposed approach. PMID- 27390200 TI - A Negative Selection Immune System Inspired Methodology for Fault Diagnosis of Wind Turbines. AB - High operational and maintenance costs represent as major economic constraints in the wind turbine (WT) industry. These concerns have made investigation into fault diagnosis of WT systems an extremely important and active area of research. In this paper, an immune system (IS) inspired methodology for performing fault detection and isolation (FDI) of a WT system is proposed and developed. The proposed scheme is based on a self nonself discrimination paradigm of a biological IS. Specifically, the negative selection mechanism [negative selection algorithm (NSA)] of the human body is utilized. In this paper, a hierarchical bank of NSAs are designed to detect and isolate both individual as well as simultaneously occurring faults common to the WTs. A smoothing moving window filter is then utilized to further improve the reliability and performance of the FDI scheme. Moreover, the performance of our proposed scheme is compared with another state-of-the-art data-driven technique, namely the support vector machines (SVMs) to demonstrate and illustrate the superiority and advantages of our proposed NSA-based FDI scheme. Finally, a nonparametric statistical comparison test is implemented to evaluate our proposed methodology with that of the SVM under various fault severities. PMID- 27390201 TI - Incremental Hashing for Semantic Image Retrieval in Nonstationary Environments. AB - A very large volume of images is uploaded to the Internet daily. However, current hashing methods for image retrieval are designed for static databases only. They fail to consider the fact that the distribution of images can change when new images are added to the database over time. The changes in the distribution of images include both discovery of a new class and a distribution of images within a class owing to concept drift. Retraining of hash tables using all images in the database requires a large computation effort. This is also biased to old data owing to the huge volume of old images which leads to a poor retrieval performance over time. In this paper, we propose the incremental hashing (ICH) method to deal with the two aforementioned types of changes in the data distribution. The ICH uses a multihashing to retain knowledge coming from images arriving over time and a weight-based ranking to make the retrieval results adaptive to the new data environment. Experimental results show that the proposed method is effective in dealing with changes in the database. PMID- 27390202 TI - Control Synthesis of Discrete-Time T-S Fuzzy Systems: Reducing the Conservatism Whilst Alleviating the Computational Burden. AB - The augmented multi-indexed matrix approach acts as a powerful tool in reducing the conservatism of control synthesis of discrete-time Takagi-Sugeno fuzzy systems. However, its computational burden is sometimes too heavy as a tradeoff. Nowadays, reducing the conservatism whilst alleviating the computational burden becomes an ideal but very challenging problem. This paper is toward finding an efficient way to achieve one of satisfactory answers. Different from the augmented multi-indexed matrix approach in the literature, we aim to design a more efficient slack variable approach under a general framework of homogenous matrix polynomials. Thanks to the introduction of a new extended representation for homogeneous matrix polynomials, related matrices with the same coefficient are collected together into one sole set and thus those redundant terms of the augmented multi-indexed matrix approach can be removed, i.e., the computational burden can be alleviated in this paper. More importantly, due to the fact that more useful information is involved into control design, the conservatism of the proposed approach as well is less than the counterpart of the augmented multi indexed matrix approach. Finally, numerical experiments are given to show the effectiveness of the proposed approach. PMID- 27390203 TI - [Studies on the unaffected relatives of schizophrenia patients - towards endophenotypic markers - Editorial]. PMID- 27390204 TI - [The potential use of ayahuasca in psychiatry]. AB - Ayahuasca is a decoctum made of admixture plants containing dimethyltryptamine and harmine. For millennia it has been used as a central element of spiritual, religious, initiation, and other - foremost healing - rituals, originally by the indigenous groups of the Amazon basin and later by the mestizo populations of the region. During the last two decades the brew has raised increased scientific and lay interest about its healing potentials within the framework of Western therapeutic settings. The typical ayahuasca effects consist of strong somatic reactions, vivid visions, relived personal memories, cathartic emotions, and insightful, introspective experiences when the emerging mental contents take different context and get deeper perspectives. The ayahuasca-experience can be exhausting necessitating the presence of an experienced leader for helping participants to pass difficult phases and for maximizing therapeutic benefits. No health damaging adverse effect has been confirmed thus far as result of its well structured, institutionalized use. The scientific investigation of ayahuasca is hindered by legal issues, methodical problems, and sociocultural preconceptions. The present review outlines the therapeutic potentials of ayahuasca use in psychiatry with its psychobiological and spiritual background. PMID- 27390206 TI - [Major obstacles in the development of child and adolescent psychiatry in Hungary]. AB - The author ascertains that healthy personality development faces increasingly serious obstacles and consequently the number of children in need of mental healthcare is on the rise. Child and adolescent psychiatry has drawn increasing appreciation, however, it is only formal and deficient in Hungary today and cannot assure optimal mental care according to the principles of evidence-based medicine. The author emphasizes that 75% of the first manifestation of the psychiatric disorders occurs during adolescence and young adulthood. In spite of legal regulation, several deficiencies hinder the development of children into healthy adults. The author analyses the most important obstacles in the development of child and adolescent Psychiatry. The author emphasizes the role of keypersons, describes the situation of and problems faced by Hungarian child psychiatric care. The author lists in detail the most important contradictions, deficiencies and obstacles and outlines suggestions for resolving the present crisis. The author emphasizes (1) the responsibility of institutions, and people dealing with society and children, and the disinterest of competent authorities. (2) The somatic, mental, cultural and spiritual ignorance/illiteracy among parents, teachers, healthcare workers, and the general population partly related to crises among the pedagogues. (3) The lack of holistic approach to treatment of children suffering from mental disorder. (4) The importance and the lack of knowledge concerning central nervous system function in child psychiatry. (5) Application of evidence-based medicine in child and adolescent psychiatry based on understanding the relationship between central nervous system alterations and mental functions. (6) Respecting keypersons' competence limits. (7) Immediate development of inpatient and outpatient child and adolescent psychiatry in the whole country. (8) Reform of child psychiatry board exam. (9) Development of currently missing textbooks and handbooks and promoting benefits of internet use. (10) The almost complete lack of the permanent and systematic mental health prevention in education and healthcare, especially in primary health care. (11) The ignorance of possible and achievable opportunities. Overcoming the obstacles of child and adolescent psychiatry can only be achieved by a coordinated action of dedicated child psychiatrists, child psychologists, informed parents, well trained pediatricians, district nurses, excellent teachers and other committed keypersons. PMID- 27390205 TI - Behavioural aspects of a modified crosstalk between basal ganglia and limbic system in Parkinson's disease. AB - Dysfunctions in dopaminergic neurotransmission lead to motor symptoms and cognitive impairments associated with behavioural disturbances. Parkinson's disease is a neurodegenerative disorder which is primarily characterized by an abnormal basal ganglia activity. Recently, increased attention has been directed towards the hippocampus in the development of non-motor symptoms. Given the temporal progression of the disease, dopaminergic depletion firstly affects the dorsal striatum leaving the ventral striatum relatively intact. However, it is possible that the structure and function of the hippocampus shows alterations even in early stages of Parkinson's disease. Subtle cognitive impairments occur in the earliest stages, and therefore Parkinson's disease could provide a unique model to investigate the effect of replacement therapies on a neural network with different baseline dopaminergic levels. Strong evidence suggests that dopaminergic medications improve the motor symptoms, but these medications might have disadvantageous effects on cognitive functions. In this review, we examine the role of dopaminergic changes across several cognitive and behavioural impairments observed in Parkinson's disease, with a special reference to hippocampal dysfunctions. PMID- 27390207 TI - Catatonia in disulfiram intoxication - a case report and a brief overview of the literature. AB - Catatonic syndromes could accompany a variety of psychiatric and medical conditions. The most common conditions underlying catatonia are affective disorders followed by schizophrenia, but several medical conditions including intoxications affecting the central nervous system can also present with catatonic signs and symptoms. Therapeutic doses of disulfiram could induce catatonia with or without accompanying psychosis or mood disorder. A case of disulfiram intoxication manifesting with catatonia is reported here together with a brief overview of the literature. A patient was admitted to the toxicology ward after a suicide attempt with approximately 20 g of disulfiram. On transfer to the psychiatric ward, she was sitting still, in a semi-stuporous state and displayed motiveless resistance to instructions or attempts to move (active negativism). She was unresponsive to most of the questions (mutism), occasionally verbigerated 1-2 words and stared for more than 20 seconds between shifting attention. After developing a comatosus state her treatment continued at the toxicology ward, where a contrast-enhanced computer tomography scan revealed bilateral emollition of 1.5 cm diameter in both nucleus lentiformis at the level of the third ventricle. Following treatment her condition improved and she benefited of rehabilitation facility and a second psychiatric treatment. She was discharged free of neurological and psychiatric symptoms. In conclusion, we underscore the importance of accurate diagnosis of the underlying psychiatric or medical condition when encountering a fast emerging catatonic syndrome and focus first on treating the causative condition while simultaneously attempting symptomatic treatment of catatonia. PMID- 27390208 TI - [Marchiafava-Bignami disease (Case-report)]. AB - Marchiafava-Bignami disease (MBD) is caused by damage of the corpus callosum. There are acute, subacute and chronic forms, it occurs most frequently among alcoholic patients. A variety of neurological symptoms, epileptic seizures, and coma may be associated with the disease, but the chronic form may start with acute confusion and dementia, interhemispherial disconnection syndrome or with slow progressive changes in behavior. In 2001, only 250 cases were reported, of which 200 died, 30 cases contributed to severe dementia or bed rest, and favorable outcome occured in only 20 cases. The MBD diagnosis of our patient was based on the anamnesis and cranial MRI and the treatment consisted of administration of B vitamin complex, folic acid, memantine, piracetam and haloperidol. Reviewing the international literature currently recommended therapeutic options are thiamin and folic acid. According to some authors the immediate administration of thiamine affects the outcome of the disease, and there are case reports of beneficial effects of amantadine and steroids. PMID- 27390209 TI - Calcium Revisited: New Insights Into the Molecular Basis of Long-QT Syndrome. PMID- 27390210 TI - Pace Mapping for the Identification of Focal Atrial Tachycardia Origin: A Novel Technique to Map and Ablate Difficult-to-Induce and Nonsustained Focal Atrial Tachycardia. AB - BACKGROUND: Focal atrial tachycardia (FAT) is extremely difficult to map and ablate when it is difficult to induce and nonsustained. The objective of this study is to evaluate the efficacy of pace mapping in identifying the FAT origin. METHODS AND RESULTS: The study included 7 patients with drug-refractory FAT who experienced daily multiple episodes before ablation and presented with difficult to-induce and nonsustained FAT and a distinct P wave morphology. Pace mapping was systematically performed in the areas of interest using 3-dimensional mapping to match the P wave morphology and paced intracardiac activation sequence recorded from multiple catheters. The anatomic origins of FAT were the right pulmonary vein (PV) in 3 patients, mitral annulus, crista terminalis, tricuspid annulus, and right-sided PV via a posterior conduction of previous PV isolation. In all patients, pace mapping obtained best-matched P wave morphology in >=11/12 leads of surface ECG at the successful ablation site, and paced intracardiac activation sequence was identical to that of induced FAT. Focal ablation was delivered in 4 patients, including non-PV FAT in 3 and FAT in 1, via posterior gap along the previous right-sided PV isolation, and circumferential right-sided PV isolation was performed in the other 3 patients. No FAT was induced at the end of the procedure. All patients were free of arrhythmias without antiarrhythmic drugs during the 8.4+/-5.6-month follow-up. CONCLUSIONS: The combination of paced P wave morphology and intracardiac activation sequence can be used for the identification of FAT origin in patients with difficult-to-induce and nonsustained FAT. PMID- 27390212 TI - Letter by Bartoletti et al Regarding Article, "Ablation of Persistent Atrial Fibrillation Targeting Low-Voltage Areas With Selective Activation Characteristics". PMID- 27390211 TI - Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes. AB - BACKGROUND: The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast enhanced cardiac magnetic resonance remain to be elucidated. METHODS AND RESULTS: We compared 35 athletes (80% men, age: 14-48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38+/-25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. CONCLUSIONS: Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID- 27390213 TI - Response to Letter Regarding Article, "Ablation of Persistent Atrial Fibrillation Targeting Low-Voltage Areas With Selective Activation Characteristics". PMID- 27390214 TI - Sarcoid Arthropathy: Comment on the Article by Ungprasert et al. PMID- 27390216 TI - Extramammary paget's disease mimicking localized malignancy on cervical cytology. AB - A case of Extramammary Paget's Disease (EMPD) involving the cervix mimicking cervical carcinoma on routine cervical cytology in a 66-year-old woman with a history of recurrent multifocal EMPD involving the vulva, perineum, perianal area, and rectum is reported. The patient had undergone multiple excisions and reconstructions of EMPD, however, had a benign cervical smear history and reported no vaginal bleeding. The conventional papanicolaou smear was reported as concerning for carcinoma with abundant, well preserved material illustrating highly atypical cells with anisonucleosis and dense cytoplasm and focal microacini. Gross anatomical distortion from EMPD and previous surgery precluded satisfactory outpatient colposcopic assessment. Examination under anesthesia was performed and colposcopy revealed a four quadrant high grade lesion extending into the vagina with one area suspicious for malignancy on the cervix. Directed biopsies were taken and histopathology confirmed EMPD with diffuse adenocarcinoma in situ cells infiltrating skin and mucosa of all specimens. These large pale cells were seen both a singly and in clusters of nests within the mucosa. Periodic Acid Schiff staining was positive for intracytoplasmic mucin and supportive immunohistochemistry was performed with strong reactivity in atypical cells for CK7, CEA, and Cam 5.2. There was no evidence of invasive malignancy and the patient remains under clinical surveillance. Cervical EMPD is rare but should be considered in women with abnormal cervical cytology and a history of vulval EMPD. Diagn. Cytopathol. 2016;44:931-934. (c) 2016 Wiley Periodicals, Inc. PMID- 27390215 TI - Antinociceptive and Anti-Inflammatory Effects of Ketamine and the Relationship to Its Antidepressant Action and GSK3 Inhibition. AB - Ketamine (KET), a NMDA antagonist, exerts an antidepressant effect at subanaesthetic doses and possesses analgesic and anti-inflammatory activities. We evaluated the involvement of KET antinociceptive and anti-inflammatory effects with its antidepressant action. Male Swiss mice were subjected to formalin, carrageenan-induced paw oedema and forced swimming tests, for assessing antinociceptive, anti-inflammatory and antidepressant effects. The treatment groups were as follows: control, KET (2, 5 and 10 mg/kg), lithium (LI: 5 mg/kg) and KET2 + LI5 combination. Immunohistochemistry analyses (TNF-alpha, iNOS, COX-2 and GSK3) in oedematous paws were performed. KET5 and KET10 reduced licking times in neurogenic (22 and 38%) and inflammatory (67 and 78%) phases of the formalin test, respectively, as related to controls. While LI5 inhibited the second phase by 24%, the licking time was inhibited by 26 and 59% in the KET2 + LI5 group (first and second phases). Furthermore, oedema volumes were reduced by 37 and 45% in the KET5 and KET10 groups, respectively. Oedema reductions were 29% in the LI5 group and 48% in the KET2 + LI5 group. In the forced swimming test, there were 23, 38 and 53% decreases in the immobility time in KET2, KET5 and KET10 groups, respectively. While LI5 caused no significant effect, decreases of 52% were observed with KET2 + LI5. KET also decreased TNF-alpha, iNOS, COX-2 and GSK3 immunostainings in oedematous paws, effects intensified with KET2 + LI5. We showed that KET presents antinociceptive and anti-inflammatory effects associated with its antidepressant response. Furthermore, our results indicate the close involvement of GSK3 inhibition and blockade of inflammatory responses, in the antidepressant drug effect. PMID- 27390217 TI - Implementing an Electronic Medical Record-Based Reminder for Cardiovascular Risk Screening in Rheumatoid Arthritis. AB - OBJECTIVE: Although cardiovascular disease (CVD) is the leading cause of death among individuals with rheumatoid arthritis (RA), CVD risks are not being assessed frequently and systematically in RA. We implemented an electronic medical record (EMR)-based reminder in a tertiary care center and assessed the effects of this intervention on CVD risk screening by rheumatologists and primary care providers. METHODS: The EMR reminder was implemented in December 2013 and included the most recent value and target ranges for body mass index, blood pressure (BP), and lipid profiles. It was displayed for every rheumatology and primary care visit for all patients with the International Classification of Diseases, Ninth Revision code for RA (714.0). Lipid screening rates, as well as changes in BP and obesity rates were compared pre- and postimplementation. Factors associated with lipid screening postimplementation were assessed using multivariate logistic regression. RESULTS: A total of 138 and 112 RA patients were seen in the outpatient clinics pre- and postimplementation, respectively. The demographic characteristics were similar in the pre- and postimplementation groups. Lipid screening rates were 50% preimplementation and 46% postimplementation (P = 0.58). There were no significant improvements in BP or obesity rates postimplementation. Factors associated with the higher odds of lipid screening included older age and history of diabetes mellitus. CONCLUSION: Implementing an EMR reminder did not improve CVD risk screening among RA patients. Future research is needed to identify and address barriers to CVD screening, and to educate patients and providers about RA-related risks. PMID- 27390218 TI - Lentivirus-Mediated Overexpression of MicroRNA-210 Improves Long-Term Outcomes after Focal Cerebral Ischemia in Mice. AB - AIMS: MicroRNAs play an important role in the pathogenesis of ischemic brain injury and in the repair process during postischemic condition. However, the key miRNAs and their function in these processes remain unclear. METHODS: Circulating blood MicroRNAs profiles were examined in the ischemic stroke patients. The predicted network of difference was analyzed by ingenuity pathway analysis. The key MicroRNAs were selected, and the function was further studied in a mouse ischemia model. The predicted downstream target was confirmed. RESULTS: We found that 24 MicroRNAs were differently expressed in stroke patients compared to the control (P < 0.05). Bioinformatic analysis showed a MicroRNAs regulated network with the highest score in the stroke cascade, which was consisted of 10 MicroRNAs including key hypoxia-related miR-210 and its predicted downstream target brain derived neurotrophic factor (BDNF). Lentivirus-mediated miR-210 overexpression enhanced the microvessel density and the number of neural progenitor cells in the ischemic mouse brain (P < 0.05) and improved neurobehavioral outcomes in the ischemic mouse (P < 0.05). MiR-210 upregulation increased mBDNF/proBDNF protein expression in the normal and ischemic mouse brain. The dual-luciferase reporter assay identified that BDNF was the direct target of miR-210. CONCLUSION: MiR-210 is a crucial ischemic stroke-associated MicroRNAs and a potential target for the stroke therapy. PMID- 27390219 TI - Which Doctor to Trust: A Recommender System for Identifying the Right Doctors. AB - BACKGROUND: Key opinion leaders (KOLs) are people who can influence public opinion on a certain subject matter. In the field of medical and health informatics, it is critical to identify KOLs on various disease conditions. However, there have been very few studies on this topic. OBJECTIVE: We aimed to develop a recommender system for identifying KOLs for any specific disease with health care data mining. METHODS: We exploited an unsupervised aggregation approach for integrating various ranking features to identify doctors who have the potential to be KOLs on a range of diseases. We introduce the design, implementation, and deployment details of the recommender system. This system collects the professional footprints of doctors, such as papers in scientific journals, presentation activities, patient advocacy, and media exposure, and uses them as ranking features to identify KOLs. RESULTS: We collected the information of 2,381,750 doctors in China from 3,657,797 medical journal papers they published, together with their profiles, academic publications, and funding. The empirical results demonstrated that our system outperformed several benchmark systems by a significant margin. Moreover, we conducted a case study in a real world system to verify the applicability of our proposed method. CONCLUSIONS: Our results show that doctors' profiles and their academic publications are key data sources for identifying KOLs in the field of medical and health informatics. Moreover, we deployed the recommender system and applied the data service to a recommender system of the China-based Internet technology company NetEase. Patients can obtain authority ranking lists of doctors with this system on any given disease. PMID- 27390220 TI - Parental Rheumatoid Arthritis, Child Mortality, and Case Fatality: A Nationwide Cohort Study. AB - OBJECTIVE: We have previously reported increased long-term morbidity in children of parents with rheumatoid arthritis (RA). Here we assess child mortality and case fatality in the same cohort. METHODS: All singletons born in Denmark from 1977 to 2008 were identified through linkage of Danish national registries. Cox proportional hazards models were used to calculate hazard ratios (HRs) of death from all causes among children exposed to parental RA, compared to unexposed children. Risk of death after infection or respiratory diseases was also assessed for children below the age of 5 years. RESULTS: This study followed 1,917,723 newborns for an average of 16 years. Of these, 13,556 were exposed to maternal RA and 6,330 to paternal RA. Overall mortality rates in children exposed to maternal or paternal RA did not differ from those in unexposed children (HR 0.98 [95% confidence interval (95% CI) 0.84-1.15] and 1.08 [95% CI 0.86-1.36], respectively), nor did the risk of death below the ages of 5 years, 3 years, or 1 year. In the group of children below the age of 5 years, 6,106 children of parents with RA were diagnosed with respiratory diseases and 3,320 with infectious diseases. The case fatality rate in children with these diseases was not significantly higher than in unexposed children (HR 1.11 [95% CI 0.74-1.66] and 0.84 [95% CI 0.52-1.35], respectively). CONCLUSION: Children of parents with RA had similar mortality rates as other children, as well as after diagnoses of respiratory or infectious diseases. PMID- 27390221 TI - An Effective Machine Learning Approach for Prognosis of Paraquat Poisoning Patients Using Blood Routine Indexes. AB - The early identification of toxic paraquat (PQ) poisoning in patients is critical to ensure timely and accurate prognosis. Although plasma PQ concentration has been reported as a clinical indicator of PQ poisoning, it is not commonly applied in practice due to the inconvenient necessary instruments and operation. In this study, we explored the use of blood routine indexes to identify the degree of PQ toxicity and/or diagnose PQ poisoning in patients via machine learning approach. Specifically, we developed a method based on support vector machine combined with the feature selection technique to accurately predict PQ poisoning risk status, then tested the method on 79 (42 male and 37 female; 41 living and 38 deceased) patients. The detection method was rigorously evaluated against a real-world data set to determine its accuracy, sensitivity and specificity. Feature selection was also applied to identify the factors correlated with risk status, and the results showed that there are significant differences in blood routine indexes between dead and living PQ-poisoned individuals (p-value < 0.01). Feature selection also showed that the most important correlated indexes are white blood cell and neutrophils. In conclusion, the toxicity or prognosis of PQ poisoning can be preliminarily ascertained by blood routine testing without PQ concentration data, representing an additional tool and innovative approach to assess the prognosis of PQ poisoning. PMID- 27390222 TI - Usability Evaluation of a Blood Glucose Monitoring System With a Spill-Resistant Vial, Easier Strip Handling, and Connectivity to a Mobile App: Improvement of Patient Convenience and Satisfaction. AB - BACKGROUND: Proper management of diabetes mellitus requires regular self monitoring of blood glucose (SMBG). This research evaluated the usability of the Accu-Chek(r) Guide Meter that includes a spill-resistant vial, easier strip handling, and wireless connectivity to a mobile app. METHODS: A total of 197 participants were allowed to experience typical blood glucose testing tasks on the Accu-Chek Guide Meter, review data such as last result, patterns, and target percentage on the meter and on the mobile app, and then evaluate their experience through a human factors usability survey. Participants used a 6-point agree/disagree scale to rate 34 market statement questions. RESULTS: The results of a Pearson chi-square proportions test for each of the 34 market statement questions showed a significant difference (P < .0001) between the disagree responses (1-3) and agree responses (4-6). An overwhelming majority of participants found all aspects of the system, including the test strips, strip vial, and data analysis on the meter and the mobile app, to be a good fit for their lifestyle and to provide a better testing experience. CONCLUSIONS: This study found superior usability of the new meter system over the participants' current meters in both the United States and France. PMID- 27390223 TI - Adherence to Insulin Pump Behaviors in Young Children With Type 1 Diabetes Mellitus. AB - BACKGROUND: Parents of young children are responsible for daily type 1 diabetes (T1DM) cares including insulin bolusing. For optimal insulin pump management, parents should enter a blood glucose result (SMBG) and a carbohydrate estimate (if food will be consumed) into the bolus advisor in their child's pump to assist in delivering the recommended insulin bolus. Previously, pump adherence behaviors were described in adolescents; we describe these behaviors in a sample of young children. METHODS: Pump data covering between 14-30 consecutive days were obtained for 116 children. Assessed adherence to essential pump adherence behaviors (eg, SMBG, carbohydrate entry, and insulin use) and adherence to 3 Wizard/Bolus Advisor steps: SMBG-carbohydrate entry-insulin bolus delivered. RESULTS: Parents completed SMBG >=4 times on 99% of days, bolused insulin >=3 times on 95% of days, and entered carbohydrates >=3 times on 93% of days, but they corrected for hyperglycemia (>=250 mg/dl or 13.9 mmol/l) only 63% of the time. Parents completed Wizard/Bolus Advisor steps (SMBG, carbohydrate entry, insulin bolus) within 30 minutes for 43% of boluses. Inverse correlations were found between children's mean daily glucose and the percentage of days with >=4 SMBG and >=3 carbohydrate entries as well as the percentage of boluses where all Wizard/Bolus Advisor steps were completed. CONCLUSIONS: Parents of young children adhered to individual pump behaviors, but showed some variability in their adherence to Wizard/Bolus Advisor steps. Parents showed low adherence to recommendations to correct for hyperglycemia. Like adolescents, targeting pump behaviors in young children may have the potential to optimize glycemic control. PMID- 27390224 TI - The Difference Between the Healing and the Nonhealing Diabetic Foot Ulcer: A Review of the Role of the Microcirculation. AB - BACKGROUND: Diabetic foot disease carries a high morbidity and is a leading cause of lower limb amputation. This may in part be due to the effect diabetes mellitus (DM) has on the microcirculation including in the skin. METHOD: We conducted a review of studies that have examined the relationship between microcirculatory function and wound healing in patients with DM. A search of the Medline, Embase, and Web of Science databases was performed coupled with a review of references for the period 1946 to March 2015. RESULTS: Nineteen studies of diverse methodology and cohort selection were identified. Poor function of the microcirculation was related to poor outcome. Transcutaneous oxygen pressure (TcPO2) was the most commonly used method to measure the microcirculation and thresholds for poor outcome proposed ranged from 10 mmHg to <34 mmHg. Two studies reexamined microcirculatory function following revascularization. Both found an increase in TcPO2, however only 1 reached statistical significance. No significant difference in the results of microcirculation tests was found between diabetic and nondiabetic patients. CONCLUSIONS: While it is not possible to draw firm conclusions from the evidence currently available there are clear areas that warrant research. Good microcirculation unsurprisingly appears to associate with better wound healing. The influence of DM is not clear, and neither is the degree of improvement required to achieve healing. Studies that examine a clearly defined cohort both with and without DM are urgently required. Accurate quantitative assessment of microcirculation will aid prediction of wound healing identifying those at greatest risk of amputation. PMID- 27390225 TI - Prevalence of Axial Spondyloarthritis Among Patients With Fibromyalgia: A Magnetic Resonance Imaging Study With Application of the Assessment of SpondyloArthritis International Society Classification Criteria. AB - OBJECTIVE: To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. METHODS: Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA-B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. RESULTS: Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. CONCLUSION: Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities. PMID- 27390226 TI - Using Competency-Based Digital Open Learning Activities to Facilitate and Promote Health Professions Education (OLAmeD): A Proposal. AB - BACKGROUND: Traditional learning in medical education has been transformed with the advent of information technology. We have recently seen global initiatives to produce online activities in an effort to scale up learning opportunities through learning management systems and massive open online courses for both undergraduate and continued professional education. Despite the positive impact of such efforts, factors such as cost, time, resources, and the specificity of educational contexts restrict the design and exchange of online medical educational activities. OBJECTIVE: The goal is to address the stated issues within the health professions education context while promoting learning by proposing the Online Learning Activities for Medical Education (OLAmeD) concept which builds on unified competency frameworks and generic technical standards for education. METHODS: We outline how frameworks used to describe a set of competencies for a specific topic in medical education across medical schools in the United States and Europe can be compared to identify commonalities that could result in a unified set of competencies representing both contexts adequately. Further, we examine how technical standards could be used to allow standardization, seamless sharing, and reusability of educational content. RESULTS: The entire process of developing and sharing OLAmeD is structured and presented in a set of steps using as example Urology as a part of clinical surgery specialization. CONCLUSIONS: Beyond supporting the development, sharing, and repurposing of educational content, we expect OLAmeD to work as a tool that promotes learning and sets a base for a community of medical educational content developers across different educational contexts. PMID- 27390227 TI - Impact of type 2 diabetes mellitus on recurrent myocardial infarction in China. AB - To evaluate the influence of type 2 diabetes mellitus on the long-term outcomes of Chinese patients with previous myocardial infarction, we studied 864 patients with previous myocardial infarction, including 251 with type 2 diabetes mellitus and 613 without type 2 diabetes mellitus, over a median follow-up time of 2.9 years. The type 2 diabetes mellitus patients were subdivided into 95 insulin treated diabetes mellitus and 156 non-insulin-treated diabetes mellitus subjects. The crude incidences (per 1000 patient-years) in the type 2 diabetes mellitus subjects versus the non-type 2 diabetes mellitus subjects were 43.7 versus 25.1 for recurrent myocardial infarction, 68.7 versus 28.3 for all-cause death and 99.8 versus 49.9 for the composite end point (i.e. recurrent myocardial infarction or all-cause death). Cox regression analysis showed that the adjusted hazard ratios for recurrent myocardial infarction, all-cause death and their combination were 1.67 (95% confidence interval: 1.06-2.74), 1.90 (1.25-2.90) and 1.72 (1.23-2.40), respectively. Significant associations were also observed between insulin treatment and all-cause death. Our findings suggested that type 2 diabetes mellitus is an independent risk factor for recurrent myocardial infarction, all-cause death and the composite end point among previous myocardial infarction patients. PMID- 27390228 TI - Motivating Students in the 21st Century. AB - PURPOSE: To examine instructors' and students' perspectives on motivation in the classroom and clinical environments and to explore instructional strategies educators can use to motivate college students in the 21st century. METHODS: Articles selected for this review were from peer-reviewed journals and scholarly sources that emphasized student and educator perspectives on motivation and instructional strategies to increase student motivation. RESULTS: Understanding how college students are motivated can help educators engage students in lessons and activities, ultimately improving the students' academic performance. DISCUSSION: Students exhibit increased motivation in classes when educators have high expectations, conduct an open-atmosphere classroom, and use multidimensional teaching strategies. Instructional styles such as connecting with students, creating an interactive classroom, and guiding and reminding students improved student motivation. CONCLUSION: Radiologic science educators must be mindful of how college students are motivated and use various instructional strategies to increase students' motivation in the classroom and clinical setting. PMID- 27390229 TI - Relationship Between the Number of Clinical Sites in Radiography Programs and Job Placement Rates of Graduates. AB - PURPOSE: To determine whether a relationship exists between the number of clinical sites available in radiography programs accredited by the Joint Review Committee on Education in Radiologic Technology and the job placement rates of graduates. METHODS: We performed a secondary analysis of data on job placement rates and the number of clinical sites available in 438 degree-granting radiography programs from January 2015 to March 2015. RESULTS: A weak, negative, nonsignificant correlation existed between the number of clinical sites and the job placement rate (Spearman's rho = -.113, n = 438, P = .018). The coefficient of determination was 1.28%.Discussion Research evaluating factors contributing to graduate employability is limited but indicates no need for radiography program administrators to adjust clinical site numbers solely on the basis of improving graduate employability. CONCLUSION: The number of clinical sites available in a radiography program is not related to the job placement rate of its graduates. PMID- 27390231 TI - Imaging Assessment of Gunshot Injuries. AB - Gunshot wounds are the third-leading cause of injury-related death nationwide. Most people with gunshot injuries undergo diagnostic imaging to evaluate their injuries in the clinical or forensic setting. Radiologic technologists must be knowledgeable about common injuries associated with gunshot wounds. Digital radiography and computed tomography play essential roles in the assessment of gunshot injuries. When clinically indicated, magnetic resonance imaging also is a valuable imaging modality for evaluating these injuries. Radiologic technologists should obtain quality images to assist with proper assessment of gunshot injuries. PMID- 27390230 TI - X-ray Fused With Magnetic Resonance Imaging to Guide Endomyocardial Biopsy of a Right Ventricular Mass. AB - BACKGROUND: A patient with a history of cancer in remission and congestive heart failure with no acute symptoms presented for a follow-up echocardiogram. The scan revealed a new echodense mass filling his right ventricular apex. An endomyocardial biopsy guided by x-ray fused with magnetic resonance (MR) imaging (XFM) was performed. This case report outlines the steps of XFM image preparation involving MR image acquisition, processing, and coregistration with x-ray fluoroscopy. DISCUSSION: In cases of focal pathology or cardiac masses, endomyocardial biopsy can be challenging because x-ray fluoroscopy guidance offers limited visualization of soft-tissue structures. XFM overcomes this issue by overlaying high-resolution MR images onto x-ray fluoroscopy images. CONCLUSION: This case report illustrates the clinical use of XFM for endomyocardial biopsy of an apical right ventricular mass and provides a practical, step-by-step description of MR image acquisition, processing, and coregistration with fluoroscopy, as performed by the MR technologist. PMID- 27390232 TI - Post-traumatic Stress Disorder and Magnetic Resonance Imaging. AB - Although post-traumatic stress disorder (PTSD) is not fully understood, considerable research has gone into studying anatomical changes in the brain that take place with this condition. Magnetic resonance (MR) imaging can demonstrate changes in the volume of numerous brain regions, and functional MR imaging shows changes in activation when subjects are exposed to trauma-related stimuli. This article reviews current research findings on PTSD-associated brain changes and behavioral effects and discusses how PTSD affects patients of different ages. PMID- 27390233 TI - Fundamentals and More. PMID- 27390234 TI - Fundamentals and More. PMID- 27390235 TI - JRCERT Continues Its Long-standing Recognition by the U.S. Department of Education. PMID- 27390236 TI - The Importance of Patient Positioning When Using a Bowtie Filter in Computed Tomography Imaging. PMID- 27390237 TI - The Effect of Managed Care on Health Care Operations. PMID- 27390238 TI - Imaging of Osteogenesis Imperfecta Prebirth to Adolescence. PMID- 27390239 TI - Zika Virus: Implications for Medical Imaging Professionals. PMID- 27390240 TI - Radiation Protection in Computed Tomography Imaging. PMID- 27390241 TI - Mammograms: Reducing Patient Anxiety. PMID- 27390242 TI - Teaching the Line-Focus Principle to First-Year Radiography Students. PMID- 27390243 TI - How to Build a Quantitative Research Project. PMID- 27390245 TI - Brain Bleed. PMID- 27390244 TI - Patients' Emotional Needs. PMID- 27390246 TI - Computed Tomography Iterative Reconstruction Techniques. AB - For all their diagnostic value, computed tomography (CT) examinations have relatively high radiation exposure. Past efforts to decrease patient dose emphasized advances in data acquisition technology because attempts to decrease dose resulted in increased image noise from filtered back projection reconstruction techniques. Iterative reconstruction techniques lead to reduced dose and maintain image quality. Improvements in CT technology and protocols can enhance patient care, but the increased amount of data requires new methods for handling information. CT iterative reconstruction techniques present a powerful way to improve patient care and image quality. PMID- 27390247 TI - Treatment Guidelines for Rheumatologic Manifestations of Sjogren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain. AB - OBJECTIVE: The Sjogren's Syndrome Foundation clinical practice guidelines (CPGs) are designed to improve quality and consistency of care in Sjogren's syndrome by offering recommendations for management. METHODS: Management questions for the systemic manifestations of Sjogren's syndrome were posed by the CPG committee with input from patients and rheumatologists. Clinical questions were assigned to a topic review group that performed systematic reviews and data extraction and drafted guidelines. Quality of evidence and strength of recommendation were rated using the American Society of Clinical Oncology's modification of the Grading of Recommendations Assessment, Development, and Evaluation. Guideline recommendations were reviewed by a consensus expert panel (CEP) composed of 30-40 clinicians from academia and community practices, as well as registered nurses and patients, using a modified Delphi process. A CEP agreement level of 75% was set as a minimum for adoption of a guideline recommendation. RESULTS: Consensus was achieved for 19 recommendations; for 11 additional modules, available data were insufficient to allow a recommendation to be formulated. Of the 19 recommendations, 15 required 1 Delphi round, 2 required 2 rounds, and 2 required 3 rounds. CONCLUSION: Key recommendations include a decision tree for the use of oral disease-modifying antirheumatic drugs for inflammatory musculoskeletal pain, use of self-care measures and advice regarding exercise to reduce fatigue, and the use of rituximab in selected clinical settings for oral and ocular dryness and for certain extraglandular manifestations, including vasculitis, severe parotid swelling, inflammatory arthritis, pulmonary disease, and mononeuritis multiplex. The CPG committee strongly discouraged the use of tumor necrosis factor inhibitors for sicca symptoms and for the majority of clinical contexts in primary Sjogren's syndrome. PMID- 27390249 TI - Evaluating the toxicity of bDtBPP on CHO-K1 cells for testing of single-use bioprocessing systems considering media selection, cell culture volume, mixing, and exposure duration. AB - Single-use bioprocessing bags are gaining popularity due to ease of use, lower risk of contamination, and ease of process scale-up. Bis(2,4-di-tert butylphenyl)phosphate (bDtBPP), a degradant of tris(2,4-di-tert butylphenyl)phosphite, marketed as Irgafos 168(r), which is an antioxidant stabilizer added to resins, has been identified as a potentially toxic leachate which may impact the performance of single-use, multilayer bioprocessing bags. In this study, the toxicity of bDtBPP was tested on CHO-K1 cells grown as adherent or suspended cells. The EC50 (effective concentration to cause 50% cell death) for adherent cells was found to be one order of magnitude higher than that for suspended CHO-K1 cells. While CHO-K1 cells had good cell viability when exposed to moderate concentrations of bDtBPP, the degradant was shown to impact the viable cell density (VCD) at much lower concentrations. Hence, in developing an industry-standard assay for testing the cytotoxicity of leachates, suspended cells (as commonly used in the bioprocessing industry) would likely be most sensitive, particularly when reporting EC50 values based on VCD. The effects of mixing, cell culture volume, and exposure duration were also evaluated for suspended CHO-K1 cells. It was found that the sensitivity of cell culture to leachates from single-use plastic bags was enhanced for suspended cells cultured for longer exposure times and when the cells were subjected to continuous agitation, both of which are important considerations in the production of biopharmaceuticals. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1318-1323, 2016. PMID- 27390248 TI - Depression and Progression of Subclinical Cardiovascular Disease in Systemic Lupus Erythematosus. AB - OBJECTIVE: Women with systemic lupus erythematosus (SLE) have an increased incidence of premature cardiovascular disease (CVD). A relationship between depression and increased inflammation leading to CVD has been proposed. The aim of this study was to evaluate the relationship between depression and the progression of subclinical atherosclerosis in women with SLE. METHODS: In this prospective case-control study, 149 participants with SLE and 126 controls were followed over 5 years. Evaluation included laboratory studies, assessment of CVD risk factors, depression screening, ultrasound evaluations of carotid intima media thickness (CIMT) and carotid plaque, and assessment of SLE disease activity for the SLE cases. RESULTS: The SLE group had a higher rate of depression: 29% compared with 11% in the control group (P = 0.003). When controlling for traditional CVD risk factors, the presence of baseline depression correlated with increased progression of CIMT in the SLE group, but not in the control group. The mean increase in CIMT was 0.026 mm in the SLE group without depression versus 0.064 mm in the depressed SLE group (P = 0.0096). There was no association between depression and carotid plaque in either group, with a calculated odds ratio for plaque progression in the depressed SLE group of 1.118 (95% confidence interval 0.476, 2.623) in the adjusted model. CONCLUSION: Women with SLE and concomitant depression have an increased risk of developing subclinical atherosclerosis, as measured by CIMT, but not by carotid plaque. The data suggest that depression, a potentially modifiable risk factor, may contribute to the increased risk of subclinical atherosclerosis in women with SLE. PMID- 27390250 TI - Activities of daily living and rehabilitation needs for older adults with a stroke: A comparison of home care and nursing home care. AB - AIM: To compare the changes in benefit levels of activities of daily living (ADLs), rehabilitation, and long-term care services (LTCS) in older adults with a stroke in different modalities of LTCS, which include home care and nursing home care. METHODS: This study analyzed national data regarding LTCS from 2008 to 2009 in South Korea. The data about 7668 older adults with a stroke were extracted from a pool of 182,535 total beneficiaries. In order to control for the baseline differences between older adults who received home care and those who received nursing home care, propensity score matching (PSM) was carried out and there were 1099 matched pairs of participants ( n = 2198). After the PSM, the changes in ADLs and rehabilitation between the two groups were analyzed by using a paired t test and the changes in LTCS benefit levels were compared by using the chi2 test. RESULTS: The ADLs and rehabilitation needs of the older adults who received home care improved, while the older adults who received nursing home care experienced deterioration. After 1 year, the LTCS benefit levels were significantly different between the home care and the nursing home care groups CONCLUSION: All of the ADLs, rehabilitation needs, and LTCS benefit levels for 1 year had improved in the home care patients, while they worsened in those who received nursing home care. This finding provides evidence to direct the policy of LTCS and offers information to guide older adults with a stroke and their family when deciding between the modalities of LTCS. PMID- 27390251 TI - Detection of phenazepam in illicitly manufactured Erimin 5 tablets. AB - A validated ultra-high-performance liquid chromatographic (UHPLC) method was used to determine the phenazepam dosage in clandestinely produced Erimin 5 tablets. Tablets from five different seizures submitted to the laboratory in 2013 were found to have a dosage of about 2.4 milligrams. The measurement uncertainty of the assay was estimated to be 3.2 % (relative) at a coverage factor of k=2. As an adjunct study the dyes in the tablets from several seizures were determined by thin-layer chromatography (TLC) for future comparative studies. PMID- 27390252 TI - New insights for identification of doping with recombinant human erythropoietin micro-doses after high hydration. AB - To minimize the chances of being caught after doping with recombinant human erythropoietins (rhEPO), athletes have turned to new practices using micro-doses and excess fluid ingestion to accelerate elimination and decrease the probability of detection. Our objective was to test the sensitivity of detection by validated methods (IEF: isoelectric focusing; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis) when such practices are used. First, after a three-week rhEPO boost period and 10 days of wash out, detection of a single 900 IU micro-dose of Eprex(r) was evaluated in healthy male subjects. After an injection in the evening, urine and plasma samples were collected the following morning. Half of the subjects then drank a bolus of water and new samples were collected 80 min later. Interestingly, rhEPO was detected in 100% of the samples even after water ingestion. A second similar protocol was then performed with a single injection of a micro-dose of rhEPO (500 IU or 900 IU), without a prior rhEPO boost. In addition, urine and plasma samples were also collected 15 and 20 h post rhEPO administration. Once again drinking water did not affect the rate of detection. Urine appeared a better matrix to detect micro-doses after 10 h, enabling between 92% and 100% of identification at that time. The rate of identification decreased rapidly thereafter, in particular for the 500 IU micro dose. However IEF analysis still resulted in 71% identification of rhEPO in urine after 20 h. These results could help to define a better strategy for controlling and identifying athletes using rhEPO micro-doses. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27390253 TI - Rationales and treatment approaches underpinning the use of acupuncture and related techniques for plantar heel pain: a critical interpretive synthesis. AB - BACKGROUND: Acupuncture shows promise as a treatment for plantar heel pain (PHP) or plantar fasciitis (PF), but data heterogeneity has undermined demonstration of efficacy. Recognising that acupuncture is a diverse field of practice, the aim of this study was to gain a broader, global perspective on the different approaches and rationales used in the application of acupuncture in PHP. METHODS: We built upon an earlier systematic review (which was limited by the necessity of a methodological focus on efficacy) using the critical interpretive synthesis (CIS) method to draw upon a wider international sample of 25 clinical sources, including case reports and case series. Multiple tracks of analysis led to an emergent synthesis. RESULTS: Findings are presented at three levels: primary (summarised data); secondary (patterns observed); and tertiary (emergent synthesis). Multiple treatments and rationales were documented but no single approach dominated. Notable contradictions emerged such as the application of moxibustion by some authors and ice by others. Synthesis of findings revealed a 'patchwork' of factors influencing the approaches taken. CONCLUSIONS: The complexity of the field of acupuncture was illustrated through the 'lens' of PHP. The 'patchwork' metaphor provides a unifying framework for a previously divergent community of practice and research. Several directions for future research were identified, such as: importance of prior duration; existence of diagnostic subgroups; and how practitioners make clinical decisions and report their findings. CIS was found to provide visibility for multiple viewpoints in developing theory and modelling the processes of 'real world' practice by acupuncturists addressing the problem of PHP. PMID- 27390254 TI - Acupuncture for chronic central serous chorioretinopathy: a prospective case series. AB - OBJECTIVE: The aim of this prospective observational study was to evaluate the effects of acupuncture at Erjian on chronic central serous chorioretinopathy (CSC). STUDY DESIGN: Prospective case series. METHODS: Nine patients with chronic CSC were recruited and each patient received 12 sessions of acupuncture treatment. Subjective symptom measures included complications, best-corrected visual acuity (BCVA), fluorescein leakage (via fluorescein fundus angiography), and central subfield foveal subretinal fluid (on optical coherence tomography (OCT)) at 3 months. Successful treatment was defined as the complete resolution of subretinal fluid observed by the OCT following completion of treatment. RESULTS: After 2 months of treatment, two patients showed improvements in visual acuity, a significant reduction in subretinal fluid and an improvement in BCVA to 0.5+/-0.10 (mean+/-SD). By contrast, four patients experienced no significant changes. After 3 months of treatment, four patients showed improvements in visual acuity and complete resolution of the subretinal fluid (mean BCVA=0.6), while parameters in two patients remained unchanged. Compared to baseline (before treatment), the proportions of patients experiencing visual improvement at 2 and 3 months were 33% (n=2) and 67% (n=4), respectively. No major complications were observed during the treatment course. CONCLUSIONS: Acupuncture might be a promising supplementary therapy for patients with CSC. However, this is ultimately only an exploratory study with a small sample size and no untreated comparator group to control for the natural history of the condition. Randomised controlled trials will be needed to demonstrate the efficacy and effectiveness of this approach. PMID- 27390255 TI - Are baseline characteristics related to responses to acupuncture treatment for musculoskeletal conditions? Analysis of a dataset from a teaching centre. PMID- 27390256 TI - GetReal: from efficacy in clinical trials to relative effectiveness in the real world. AB - The GetReal consortium ("incorporating real-life data into drug development") addresses the efficacy-effectiveness gap that opens between the data from well controlled randomized trials in selected patient groups submitted to regulators and the real-world evidence on effectiveness and safety of drugs required by decision makers. Workpackage 4 of GetReal develops evidence synthesis and modelling approaches to generate the real-world evidence. In this commentary, we discuss how questions change when moving from the well-controlled randomized trial setting to real-life medical practice, the evidence required to answer these questions, the populations to which estimates will be applicable to and the methods and data sources used to produce these estimates. We then introduce the methodological reviews written by GetReal authors and published in Research Synthesis Methods on network meta-analysis, individual patient data meta-analysis and mathematical modelling to predict drug effectiveness. The critical reviews of key methods are a good starting point for the ambitious programme of work GetReal has embarked on. The different strands of work under way in GetReal have great potential to contribute to making clinical trials research as relevant as it can be to patients, caregivers and policy makers. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27390257 TI - Outcome Expectations and Osteoarthritis: Association of Perceived Benefits of Exercise With Self-Efficacy and Depression. AB - OBJECTIVE: Outcome expectancy is recognized as a determinant of exercise engagement and adherence. However, little is known about which factors influence outcome expectations for exercise among people with knee osteoarthritis (OA). This is the first study to examine the association of outcome expectations for exercise with demographic, physical, and psychosocial outcomes in individuals with knee OA. METHODS: We performed a cross-sectional analysis of the baseline data from a randomized trial of tai chi versus physical therapy in participants with symptomatic knee OA. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Outcome expectations for exercise, self-efficacy, depression, anxiety, stress, and social support were measured using standard instruments. Logistic regression models were utilized to determine associations with outcome expectations. RESULTS: There were 262 participants, with a mean age of 59.8 years and a mean body mass index of 32.1 kg/m2 ; 69.1% of the participants were female, 51.5% were white, the mean disease duration was 8.6 years, and the mean WOMAC knee pain and function scores were 260.8 and 906.8, respectively. Higher outcome expectations for exercise were associated with greater self-efficacy (odds ratio [OR] 1.25 [95% confidence interval (95% CI) 1.11-1.41]; P = 0.0004), as well as with fewer depressive symptoms (OR 0.84 for each 5-point increase [95% CI 0.73-0.97]; P = 0.01). Outcome expectancy was not significantly associated with sex, race, education, pain, function, radiographic severity, social support, anxiety, or stress. CONCLUSION: Our results suggest significant associations between outcome expectations for exercise and self-efficacy and depression. Future studies should examine how these relationships longitudinally affect long-term clinical outcomes of exercise-based treatment for knee OA. PMID- 27390258 TI - Docetaxel-Chitosan nanoparticles for breast cancer treatment: cell viability and gene expression study. AB - Docetaxel acts through the inhibition of tubulin polymerization and reduction in the expression of BCL-2 gene. In this study, nanoparticles containing Docetaxel were prepared and their effects on the gene expression levels of BCL-2 and BAX genes were investigated. The drug was first conjugated to chitosan, and the nanoparticles were assembled in the presence of hyaluronic acid. Conjugations were confirmed by 1 H-NMR, and the obtained nanoparticles were characterized by dynamic light scattering and SEM. Cytotoxicity of the nanoparticles, cellular uptake, and cell death were evaluated. Finally, the effect of nanoparticles on the expression of BAX and BCL-2 genes in MCF-7 cells were investigated through real-time PCR. The results revealed that the prepared NPs had spherical shape with narrow size distribution of <200 nm with positive zeta potentials. In vitro cytotoxicity of Cs nanoparticles and free Docetaxel investigations revealed that increasing the treatment time with nanoparticles led to decrease in the rate of cell viability. BAX and BCL-2 gene expressions were decreased in nanoparticle treated cells in comparison with intact cells, while the BAX/BCL-2 ratio was significantly elevated compared with free drug-treated cells after 72 h. Docetaxel-conjugated NPs may offer a promising treatment with low off-target toxicity for breast cancer. PMID- 27390259 TI - Ultrathin Metal Films with Defined Topographical Structures as In Vitro Cell Culture Platforms for Unveiling Vascular Cell Behaviors. AB - Implanted material surfaces make direct contact with body tissues to work on its own purpose. Therefore, studies of the surface properties of implantable materials that determine cell fate are very important for successful implantation. Although numerous studies have addressed the relationship between cells and material surfaces, nonmetallic surfaces and metallic surfaces likely produce different cellular responses because of their intrinsic differences in surface energy, roughness, and chemical composition. Moreover, given the nontransparent property of metal materials, which hampers the real-time imaging of cellular behavior, a detailed cellular-level analysis at the metal-tissue interface has not been performed. In this study, metal-based cell culture platforms (MCPs) with defined microscale topographical patterns are developed using a combination of photolithography and direct current magnetron sputtering techniques. The MCPs allow to observe vascular cells on metals in real time and identify the selective regulation of human aortic smooth muscle cells and Human umbilical vein endothelial cells (HUVECs) by metallic surface topography. Additionally, atomic force microscopy, contact angles, and energy-dispersive X ray spectroscopy analyses show that the MCPs exhibit nearly identical chemical properties with their bulk counterparts, demonstrating that MCPs can be utilized as an in vitro cell culture platform system for understanding the cellular behavior on metal substrates. PMID- 27390260 TI - Life-cycle and cost of goods assessment of fed-batch and perfusion-based manufacturing processes for mAbs. AB - Life-cycle assessment (LCA) is an environmental assessment tool that quantifies the environmental impact associated with a product or a process (e.g., water consumption, energy requirements, and solid waste generation). While LCA is a standard approach in many commercial industries, its application has not been exploited widely in the bioprocessing sector. To contribute toward the design of more cost-efficient, robust and environmentally-friendly manufacturing process for monoclonal antibodies (mAbs), a framework consisting of an LCA and economic analysis combined with a sensitivity analysis of manufacturing process parameters and a production scale-up study is presented. The efficiency of the framework is demonstrated using a comparative study of the two most commonly used upstream configurations for mAb manufacture, namely fed-batch (FB) and perfusion-based processes. Results obtained by the framework are presented using a range of visualization tools, and indicate that a standard perfusion process (with a pooling duration of 4 days) has similar cost of goods than a FB process but a larger environmental footprint because it consumed 35% more water, demanded 17% more energy, and emitted 17% more CO2 than the FB process. Water consumption was the most important impact category, especially when scaling-up the processes, as energy was required to produce process water and water-for-injection, while CO2 was emitted from energy generation. The sensitivity analysis revealed that the perfusion process can be made more environmentally-friendly than the FB process if the pooling duration is extended to 8 days. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1324-1335, 2016. PMID- 27390261 TI - Identification of epidermal growth factor (EGF), in an unknown pharmaceutical preparation suspected to contain insulin like growth factor 1 (IGF-1). PMID- 27390262 TI - Anxiety and diabetes: Innovative approaches to management in primary care. AB - Type 2 diabetes mellitus is a chief concern for patients, healthcare providers, and health care systems in America, and around the globe. Individuals with type 2 diabetes mellitus exhibit clinical and subclinical symptoms of anxiety more frequently than people without diabetes. Anxiety is traditionally associated with poor metabolic outcomes and increased medical complications among those with type 2 diabetes mellitus. Collaborative care models have been utilized in the multidisciplinary treatment of mental health problems and chronic disease, and have demonstrated success in managing the pathology of depression which often accompanies diabetes. However, no specific treatment model has been published that links the treatment of anxiety to the treatment of type 2 diabetes mellitus. Given the success of collaborative care models in treating depression associated with diabetes, and anxiety unrelated to chronic disease, it is possible that the collaborative care treatment of primary care patients who suffer from both anxiety and diabetes could be met with the same success. The key issue is determining how to implement and sustain these models in practice. This review summarizes the proposed link between anxiety and diabetes, and offers an innovative and evidence-based collaborative care model for anxiety and diabetes in primary care. PMID- 27390263 TI - Expression kinetics of hepatic progenitor markers in cellular models of human liver development recapitulating hepatocyte and biliary cell fate commitment. AB - Due to the limitations of research using human embryos and the lack of a biological model of human liver development, the roles of the various markers associated with liver stem or progenitor cell potential in humans are largely speculative, and based on studies utilizing animal models and certain patient tissues. Human pluripotent stem cell-based in vitro multistage hepatic differentiation systems may serve as good surrogate models for mimicking normal human liver development, pathogenesis and injury/regeneration studies. Here, we describe the implications of various liver stem or progenitor cell markers and their bipotency (i.e. hepatocytic- and biliary-epithelial cell differentiation), based on the pluripotent stem cell-derived model of human liver development. Future studies using the human cellular model(s) of liver and biliary development will provide more human relevant biological and/or pathological roles of distinct markers expressed in heterogeneous liver stem/progenitor cell populations. PMID- 27390265 TI - Molecular aspects of beta, beta-carotene-9', 10'-oxygenase 2 in carotenoid metabolism and diseases. AB - Carotenoids, the carotenes and xanthophylls, are essential components in human nutrition. beta, beta-carotene-9', 10'-oxygenase 2 (BCO2), also named as beta, beta-carotene-9', 10'-dioxygenase 2 (BCDO2) catalyzes the asymmetrical cleavage of carotenoids, whereas beta, beta-carotene-15, 15'-monooxygenase (BCMO1) conducts the symmetrical cleavage of pro-vitamin A carotenoids into retinoid. Unlike BCMO1, BCO2 has a broader substrate specificity and has been considered an alternative way to produce vitamin A. In contrast to BCMO1, a cytoplasmic protein, BCO2 is located in the inner mitochondrial membrane. The difference in cellular compartmentalization may reflect the different substrate specificity and physiological functions with respect to BCMO1 and BCO2. The BCO2 gene mutations are proven to be associated with yellow color of skin and fat tissue and milk in livestock. Mutation in intron 2 of BCO2 gene is also supposed to be related to the expression of IL-18, a pro-inflammatory cytokine associated with obesity, cardiovascular diseases, and type 2 diabetes. Further, BCO2 is associated with the development of mitochondrial oxidative stress, macular degeneration, anemia, and hepatic steatosis. This review of the literature will mostly address recent updates regarding the role of BCO2 in carotenoid metabolism, and discuss the potential impacts of BCO2 protein and the mutations in mammalian diseases. PMID- 27390267 TI - Bayesian network meta-analysis for cluster randomized trials with binary outcomes. AB - Network meta-analysis is becoming a common approach to combine direct and indirect comparisons of several treatment arms. In recent research, there have been various developments and extensions of the standard methodology. Simultaneously, cluster randomized trials are experiencing an increased popularity, especially in the field of health services research, where, for example, medical practices are the units of randomization but the outcome is measured at the patient level. Combination of the results of cluster randomized trials is challenging. In this tutorial, we examine and compare different approaches for the incorporation of cluster randomized trials in a (network) meta analysis. Furthermore, we provide practical insight on the implementation of the models. In simulation studies, it is shown that some of the examined approaches lead to unsatisfying results. However, there are alternatives which are suitable to combine cluster randomized trials in a network meta-analysis as they are unbiased and reach accurate coverage rates. In conclusion, the methodology can be extended in such a way that an adequate inclusion of the results obtained in cluster randomized trials becomes feasible. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27390264 TI - Liver metastases: Microenvironments and ex-vivo models. AB - The liver is a highly metastasis-permissive organ, tumor seeding of which usually portends mortality. Its unique and diverse architectural and cellular composition enable the liver to undertake numerous specialized functions, however, this distinctive biology, notably its hemodynamic features and unique microenvironment, renders the liver intrinsically hospitable to disseminated tumor cells. The particular focus for this perspective is the bidirectional interactions between the disseminated tumor cells and the unique resident cell populations of the liver; notably, parenchymal hepatocytes and non-parenchymal liver sinusoidal endothelial, Kupffer, and hepatic stellate cells. Understanding the early steps in the metastatic seeding, including the decision to undergo dormancy versus outgrowth, has been difficult to study in 2D culture systems and animals due to numerous limitations. In response, tissue-engineered biomimetic systems have emerged. At the cutting-edge of these developments are ex vivo 'microphysiological systems' (MPS) which are cellular constructs designed to faithfully recapitulate the structure and function of a human organ or organ regions on a milli- to micro-scale level and can be made all human to maintain species-specific interactions. Hepatic MPSs are particularly attractive for studying metastases as in addition to the liver being a main site of metastatic seeding, it is also the principal site of drug metabolism and therapy-limiting toxicities. Thus, using these hepatic MPSs will enable not only an enhanced understanding of the fundamental aspects of metastasis but also allow for therapeutic agents to be fully studied for efficacy while also monitoring pharmacologic aspects and predicting toxicities. The review discusses some of the hepatic MPS models currently available and although only one MPS has been validated to relevantly modeling metastasis, it is anticipated that the adaptation of the other hepatic models to include tumors will not be long in coming. PMID- 27390268 TI - Treat-to-Target Strategy for Fibromyalgia: Opening the Dialogue. PMID- 27390266 TI - The N-terminal extension of yeast ribosomal protein L8 is involved in two major remodeling events during late nuclear stages of 60S ribosomal subunit assembly. AB - Assaying effects on pre-rRNA processing and ribosome assembly upon depleting individual ribosomal proteins (r-proteins) provided an initial paradigm for assembly of eukaryotic ribosomes in vivo-that each structural domain of ribosomal subunits assembles in a hierarchical fashion. However, two features suggest that a more complex pathway may exist: (i) Some r-proteins contain extensions that reach long distances across ribosomes to interact with multiple rRNA domains as well as with other r-proteins. (ii) Individual r-proteins may assemble in a stepwise fashion. For example, the globular domain of an r-protein might assemble separately from its extensions. Thus, these extensions might play roles in assembly that could not be revealed by depleting the entire protein. Here, we show that deleting or mutating extensions of r-proteins L7 (uL30) and L35 (uL29) from yeast reveal important roles in early and middle steps during 60S ribosomal subunit biogenesis. Detailed analysis of the N-terminal terminal extension of L8 (eL8) showed that it is necessary for late nuclear stages of 60S subunit assembly involving two major remodeling events: removal of the ITS2 spacer; and reorganization of the central protuberance (CP) containing 5S rRNA and r-proteins L5 (uL18) and L11 (uL5). Mutations in the L8 extension block processing of 7S pre rRNA, prevent release of assembly factors Rpf2 and Rrs1 from pre-ribosomes, which is required for rotation of the CP, and block association of Sda1, the Rix1 complex, and the Rea1 ATPase involved in late steps of remodeling. PMID- 27390270 TI - Predicting subtype selectivity of dopamine receptor ligands with three dimensional biologically relevant spectrum. AB - We applied a novel molecular descriptor, three-dimensional biologically relevant spectrum (BRS-3D), in subtype selectivity prediction of dopamine receptor (DR) ligands. BRS-3D is a shape similarity profile calculated by superimposing the objective compounds against 300 template ligands from sc-PDB. First, we constructed five subtype selectivity regression models between DR subtypes D1-D2, D1-D3, D2-D3, D2-D4, and D3-D4. The models' 10-fold cross-validation-squared correlation coefficient (Q2 , for training sets) and determination coefficient (R2 , for test sets) were in the range of 0.5-0.7 and 0.6-0.8, respectively. Then, four pair-wise (D1-D2, D2-D3, D2-D4, and D3-D4) and a multitype (D2, D3, and D4) classification models were developed with the prediction accuracies around or over 90% (for test sets). Lastly, we compared the performances of the models developed on BRS-3D and classical descriptors. The results showed that BRS 3D performed similarly to classical 2D descriptors and better than other 3D descriptors. Combining BRS-3D and 2D descriptors can further improve the prediction performance. These results confirmed the capacity of BRS-3D in the prediction of DR subtype-selective ligands. PMID- 27390269 TI - G Protein-Coupled Receptor Kinases: Crucial Regulators of Blood Pressure. PMID- 27390271 TI - Functional Supramolecular Polymers: A Fluorescent Microfibrous Network in a Supramolecular Hydrogel for High-Contrast Live Cell-Material Imaging in 3D Environments. AB - A new bottom-up strategy based on aromatic peptide amphiphile is developed for a high-contrast visualization of 3D live cell-material imaging-something that has been difficult to achieve previously because of the problems associated with the diffraction of light by the nanosized peptide materials and the aggregation caused quenching of aggregated pi-conjugated fluorophores in the nanostructures. This study reports an example of a novel supramolecular hydrogelator, naphthaleneimide-phenylalanine (NI-Phe), which forms a self-supporting hydrogel displaying a unique microfibrous network and promising aggregation-induced emission characteristics at pH 7.4. The storage modulus of the NI-Phe gel supports the mass of a cell for 3D cell culturing. This work illustrates a new dopant-free supramolecular approach, complementary to well-established doping procedures that should facilitate the development of live cell imaging in 3D scaffolding materials. PMID- 27390272 TI - Duration of diabetes and types of diabetes therapy in Japanese patients with type 2 diabetes: The Japan Diabetes Complication and its Prevention prospective study 3 (JDCP study 3). AB - AIMS/INTRODUCTION: To analyze the association between the duration of diabetes and selection of diabetes therapy in a large database of Japanese patients with type 2 diabetes. MATERIALS AND METHODS: We used the data of 5,844 patients with type 2 diabetes to evaluate the association between the duration of diabetes and types of diabetes therapy. The logistic regression model was used to analyze the association between duration of diabetes and selection of diabetes therapy, and restricted cubic spline curves were used to represent the schematic association. RESULTS: Overall, clinical characteristics of the patients were women, 39.9%; mean age, 61.4 years; median duration of diabetes, 9 years; mean glycated hemoglobin, 7.4% (57.0 mmol/mol); and mean body mass index, 24.5 kg/m2 . Compared with the first quartile of diabetes duration, the multivariable-adjusted odds of any antidiabetic therapy (oral hypoglycemic agents or insulin) for the second, third and fourth quartiles were 2.17 (95% confidence interval [CI] 1.68-2.80; 3.39, 95% CI 2.53-4.54; 4.99, 95% CI 3.64-6.84), respectively (P for trend <0.001), and these associations were attenuated after adjusting possible confounders. Furthermore, those of insulin therapy were 1.48 (95% CI 1.20-1.84; 2.16, 95% CI 1.77-2.64; 4.94, 95% CI 4.04-6.04), respectively (P for trend <0.001). Schematic representation of restricted cubic spline curves analysis showed that a longer duration of diabetes was linearly associated with the odds of insulin therapy. CONCLUSIONS: Obtained data showed that a longer duration of diabetes required complex diabetes drug regimens to be introduced to patients with type 2 diabetes. PMID- 27390273 TI - The role of more than 40 years of improvement in protein A chromatography in the growth of the therapeutic antibody industry. AB - Protein A chromatography has been used as the mAb capture step in the majority of FDA submissions. In this study, the performance of protein A chromatography, as indicated by capacity, operational flow rate, and productivity (rate of mAb production per liter of resin) was examined over its full history to gain insights into the reasons for its consistent use. Protein A productivity and capacity have increased 4.3 and 5.5% a year, respectively, since 1978. In contrast, protein A operational flow rate increased between 1978 and 2001 and then remained constant or declined as further improvements provided only marginal benefits. The productivity of protein A resin and also the mAb bioreactor titer (14% growth) rapidly improved starting in about 1990 to economically provide material for clinical trials. Technology improvement is typically driven by product sales. The sales of protein A resin, as indicated by sales of protein A ligand (21% growth), have closely paralleled the sales of mAbs (20% growth). Both increased rapidly in 2000 after the first major mAb therapeutics were approved and the markets were developed. It is likely that alternatives to protein A chromatography have not been implemented because of the order of magnitude improvement in protein A performance. Protein A membrane adsorbers and monoliths have higher productivity than packed columns due to their short bed heights and high operational flow rates. These devices are not currently practical for large scale manufacturing but may represent a format for future improvements in protein A productivity. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1193-1202, 2016. PMID- 27390274 TI - High burden of prevalent tuberculosis among previously treated people in Southern Africa suggests potential for targeted control interventions. PMID- 27390275 TI - Can intermediate monocytes predict response to infliximab therapy in sarcoidosis? PMID- 27390276 TI - Predictive value of exhaled nitric oxide in healthy infants for asthma at school age. PMID- 27390277 TI - Feasibility of lung clearance index in a clinical setting in pre-school children. AB - Lung function testing in pre-school children in the clinical setting is challenging. Most cannot perform spirometry and many infant lung function tests require sedation. Lung clearance index (LCI) derived from the multiple-breath washout (MBW) test has been shown to be sensitive to early disease changes but may be time consuming and so a shortened test (LCI0.5) may be more feasible in young children. We sought to establish feasibility of MBW in unsedated pre-school children in a clinic setting and hypothesised use of LCI0.5 would increase success rates.116 pre-school children (28 healthy controls and 88 with respiratory disease), median age 4.0 years (range 2-6 years), underwent MBW tests unsedated in a clinic setting, using sulfur hexafluoride as a tracer gas and an adapted photoacoustic gas analyser.81 (70%) out of 116 children completed LCI and 72% completed LCI0.5 measurement. Test success increased significantly in patients over 3 years (0% at <2.5 years, 33% at 2.5-3 years and 70% at >3 years, p<0.0001). LCI was elevated in those with respiratory disease compared with healthy controls.MBW is feasible in a clinic setting in unsedated pre-schoolers, particularly in those >3 years old, and LCI is raised in those with respiratory disease. Use of LCI0.5 did not increase success rate in pre-schoolers. PMID- 27390278 TI - Accelerated telomere attrition in children and teenagers with alpha1-antitrypsin deficiency. AB - Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of alpha1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with alpha1 antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2-18 years) diagnosed with AATD and 18 controls (aged 3-16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and alpha1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression. PMID- 27390279 TI - Eosinophilic pneumonia associated with pirfenidone therapy. PMID- 27390280 TI - First evaluation of QuantiFERON-TB Gold Plus performance in contact screening. AB - Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-gamma release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's kappa of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-gamma production between the two antigen tubes (TB2-TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2-TB1 values >0.6 IU.mL-1 were significantly associated with proximity to the index case and European origin.QFT Plus has a stronger association with surrogate measures of TB exposure than QFT GIT in adults screened for latent TB infection. Interferon-gamma response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection. PMID- 27390281 TI - Defining a standard set of patient-centred outcomes for lung cancer. AB - In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes.The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation ("the set") on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment.The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons.We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally. PMID- 27390282 TI - Beta-blockers in COPD: time for reappraisal. AB - The combined effects on the heart of smoking and hypoxaemia may contribute to an increased cardiovascular burden in chronic obstructive pulmonary disease (COPD). The use of beta-blockers in COPD has been proposed because of their known cardioprotective effects as well as reducing heart rate and improving systolic function. Despite the proven cardiac benefits of beta-blockers post-myocardial infarction and in heart failure they remain underused due to concerns regarding potential bronchoconstriction, even with cardioselective drugs. Initiating treatment with beta-blockers requires dose titration and monitoring over a period of weeks, and beta-blockers may be less well tolerated in older patients with COPD who have other comorbidities. Medium-term prospective placebo-controlled safety studies in COPD are warranted to reassure prescribers regarding the pulmonary and cardiac tolerability of beta-blockers as well as evaluating their potential interaction with concomitant inhaled long-acting bronchodilator therapy. Several retrospective observational studies have shown impressive reductions in mortality and exacerbations conferred by beta-blockers in COPD. However, this requires confirmation from long-term prospective placebo-controlled randomised controlled trials. The real challenge is to establish whether beta blockers confer benefits on mortality and exacerbations in all patients with COPD, including those with silent cardiovascular disease where the situation is less clear. PMID- 27390283 TI - Tele-monitoring of ventilator-dependent patients: a European Respiratory Society Statement. AB - The estimated prevalence of ventilator-dependent individuals in Europe is 6.6 per 100 000 people. The increasing number and costs of these complex patients make present health organisations largely insufficient to face their needs. As a consequence, their burden lays mostly over families. The need to reduce healthcare costs and to increase safety has prompted the development of tele monitoring for home ventilatory assistance.A European Respiratory Society Task Force produced a literature research based statement on commonly accepted clinical criteria for indications, follow-up, equipment, facilities, legal and economic issues of tele-monitoring of these patients.Many remote health monitoring systems are available, ensuring safety, feasibility, effectiveness, sustainability and flexibility to face different patients' needs. The legal problems associated with tele-monitoring are still controversial. National and European Union (EU) governments should develop guidelines and ethical, legal, regulatory, technical, administrative standards for remote medicine. The economic advantages, if any, of this new approach must be compared to a "gold standard" of home care that is very variable among different European countries and within each European country.Much more research is needed before considering tele monitoring a real improvement in the management of these patients. PMID- 27390284 TI - Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal disease of unknown aetiology. A growing body of evidence supports that IPF represents an epithelial-driven process characterised by aberrant epithelial cell behaviour, fibroblast/myofibroblast activation and excessive accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The mechanisms involved in the abnormal hyper-activation of the epithelium are unclear, but we propose that recapitulation of pathways and processes critical to embryological development associated with a tissue specific age-related stochastic epigenetic drift may be implicated. These pathways may also contribute to the distinctive behaviour of IPF fibroblasts. Genomic and epigenomic studies have revealed that wingless/Int, sonic hedgehog and other developmental signalling pathways are reactivated and deregulated in IPF. Moreover, some of these pathways cross-talk with transforming growth factor-beta activating a profibrotic feedback loop. The expression pattern of microRNAs is also dysregulated in IPF and exhibits a similar expression profile to embryonic lungs. In addition, senescence, a process usually associated with ageing, which occurs early in alveolar epithelial cells of IPF lungs, likely represents a conserved programmed developmental mechanism. Here, we review the major developmental pathways that get twisted in IPF, and discuss the connection with ageing and potential therapeutic approaches. PMID- 27390285 TI - Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study. AB - While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L.min(-1).m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients. PMID- 27390287 TI - Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold Hopping Approach. AB - Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold-hopping approach. Structure-activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time-dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P-glycoprotein (Pgp)-mediated efflux. Compound 80 c [{(1S,6R)-3-(6,7-difluoroquinoxalin-2-yl)-3,8 diazabicyclo[4.2.0]octan-8-yl}(4-methyl-[1,1'-biphenyl]-2-yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium-release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep-promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant. PMID- 27390288 TI - Deja vu ... All Over Again. PMID- 27390289 TI - Revision Tibiotalocalcaneal Arthrodesis With a Pseudoelastic Intramedullary Nail. AB - : Hindfoot (tibiotalocalcaneal or TTC) arthrodesis is commonly used to treat concomitant arthritis of the ankle and subtalar joints. Simultaneous fusion of both joints can be difficult to achieve especially in patients with impaired healing due to smoking, diabetes mellitus, or Charcot neuroarthropathy. Conventional intramedullary fixation devices allow for compression to be applied at the time of surgery, but this compression can be lost due to bone resorption or settling, leading to impaired healing. In contrast, the novel pseudoelastic intramedullary nail is designed to maintain compression at the arthrodesis sites throughout the healing process by the use of an internal pseudoelastic element. We present 2 cases of revision TTC arthrodesis using the pseudoelastic intramedullary nail. In the first case, an 80-year-old diabetic man with previous ankle and failed subtalar fusion with screws underwent revision TTC arthrodesis. In the second case, a 66-year-old man with Charcot neuroarthropathy and a failed TTC arthrodesis with a static intramedullary nail underwent revision tibiotalar arthrodesis. In both cases, computed tomography scan demonstrated successful union and patients were allowed full weight bearing by 3 months after surgery. These cases provide early evidence that sustained compression via an intramedullary nail can lead to rapid successful hindfoot fusion when standard approaches have failed. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case study. PMID- 27390286 TI - Pilot Mouse Study of 1 mm Inner Diameter (ID) Vascular Graft Using Electrospun Poly(ester urea) Nanofibers. AB - An off-the-shelf, small diameter tissue engineered vascular graft (TEVG) would be transformative to surgeons in multiple subspecialties. Herein, the results of a small diameter (ID ~ 1 mm) vascular graft constructed from resorbable, amino acid based poly(ester urea) (PEU) are reported. Electrospun PEU grafts of two different wall thicknesses (type A: 250 MUm; type B: 350 MUm) are implanted as abdominal infra-renal aortic grafts in a severe combined immune deficient/beige mouse model and evaluated for vessel remodeling over one year. Significantly, the small diameter TEVG does not rupture or lead to acute thrombogenic events during the intervals tested. The pilot TEVG in vivo shows long-term patency and extensive tissue remodeling with type A grafts. Extensive tissue remodeling in type A grafts leads to the development of well-circumscribed neovessels with an endothelial inner lining, a neointima containing smooth muscle cells. However, due to slow degradation of the PEU scaffold materials in vivo, the grafts remain after one year. The type B grafts, which have 350 MUm thick walls, experience occlusion over the one year interval due to intimal hyperplasia. This study affords significant findings that will guide the design of future generations of small diameter vascular grafts. PMID- 27390290 TI - Measurement of Nitinol Recovery Distance Using Pseudoelastic Intramedullary Nails for Tibiotalocalcaneal Arthrodesis. AB - BACKGROUND: Tibiotalocalcaneal arthrodesis is a salvage procedure for patients with complex disease of the ankle and subtalar joints. Despite the clinical efficacy and mechanical advantage of intramedullary nails, complications, such as nonunion, are common. It may be possible to sustain compression in the face of bone resorption and implant loosening over the course of healing using a novel pseudoelastic intramedullary nail with an internal nitinol element. METHODS: We identified 15 patients with average age of 54.7 years (range, 28-75 years) who had undergone a tibiotalocalcaneal arthrodesis using a pseudoelastic intramedullary nail. Serial radiographs were used to determine the amount and rate of nitinol element migration over the first 3 postoperative months. RESULTS: Postoperatively, there was at least 2.38 mm of nitinol element migration proximally with mean of 5.58 mm (+/- 1.38), (range, 2.38-8.11 mm). Average follow up time was 195 days (+/- 106.3), (range, 89-490 days). On average, 86% of the total recovered distance took place within the first 39.7 days (+/-10.03). CONCLUSIONS: The nitinol element recovers distance when stretched intraoperatively and maintains moderate compression in response to bone resorption. Further studies are needed to assess if this increased compression lends itself to higher fusion rates than traditional intramedullary nails. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case series. PMID- 27390291 TI - Programmed Nanoparticles for Tailoring the Detection of Inflammatory Bowel Diseases and Irritable Bowel Syndrome Disease via Breathprint. AB - Chemical sensors based on programmable molecularly modified gold nanoparticles are tailored for the detection and discrimination between the breathprint of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The sensors are examined in both lab- and real-world clinical conditions. The results reveal a discriminative power accuracy of 81% between IBD and IBS and 75% between Crohn's and Colitis states. PMID- 27390292 TI - A small molecule identified through an in silico screen inhibits Aurora B-INCENP interaction. AB - Aurora B is a serine/threonine kinase that has a central role in the regulation of mitosis. The observation of Aurora B overexpression in cancer makes it a promising target to develop antitumoral inhibitors. We describe a new potential inhibitor that exclusively targets the interaction site of Aurora B and its activator INCENP. We performed a structure-based virtual screening and determined five potential candidates of 200 000 compounds, which selectively bind to the Aurora B::INCENP interaction site, but not to the ATP-binding site (kinase pocket) of Aurora B or other related kinases. Further characterization in vivo validated the inhibitory role of one of these five compounds in Aurora B::INCENP complex formation and exhibited hallmarks of Aurora inhibition such as chromosome congression and segregation defects that interfere with the progression into cytokinesis and result in multinuclear cells. Our results provide an alternative approach on the way of exploring specific kinase inhibitors. PMID- 27390293 TI - Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active Systemic Lupus Erythematosus. AB - OBJECTIVE: To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. METHODS: Sixty-seven patients with active SLE, mean +/- SD age 39.3 +/- 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24 hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). RESULTS: Mean +/- SD followup was 16.2 +/- 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24 hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. CONCLUSION: Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE. PMID- 27390294 TI - Techno-economic analysis for incorporating a liquid-liquid extraction system to remove acetic acid into a proposed commercial scale biorefinery. AB - Mitigating the effect of fermentation inhibitors in bioethanol plants can have a great positive impact on the economy of this industry. Liquid-liquid extraction (LLE) using ethyl acetate is able to remove fermentation inhibitors-chiefly, acetic acid-from an aqueous solution used to produce bioethanol. The fermentation broth resulting from LLE has higher performance for ethanol yield and its production rate. Previous techno-economic analyses focused on second-generation biofuel production did not address the impact of removing the fermentation inhibitors on the economic performance of the biorefinery. A comprehensive analysis of applying a separation system to mitigate the fermentation inhibition effect and to provide an analysis on the economic impact of removal of acetic acid from corn stover hydrolysate on the overall revenue of the biorefinery is necessary. This study examines the pros and cons associated with implementing LLE column along with the solvent recovery system into a commercial scale bioethanol plant. Using details from the NREL-developed model of corn stover biorefinery, the capital costs associated with the equipment and the operating cost for the use of solvent were estimated and the results were compared with the profit gain due to higher ethanol production. Results indicate that the additional capital will add 1% to the total capital and manufacturing cost will increase by 5.9%. The benefit arises from the higher ethanol production rate and yield as a consequence of inhibitor extraction and results in a $0.35 per gallon reduction in the minimum ethanol selling price (MESP). (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:971-977, 2016. PMID- 27390295 TI - An Autotaxin/Lysophosphatidic Acid/Interleukin-6 Amplification Loop Drives Scleroderma Fibrosis. AB - OBJECTIVE: We previously implicated the lipid mediator lysophosphatidic acid (LPA) as having a role in dermal fibrosis in systemic sclerosis (SSc). The aim of this study was to identify the role of the LPA-producing enzyme autotaxin (ATX), and to connect the ATX/LPA and interleukin-6 (IL-6) pathways in SSc. METHODS: We evaluated the effect of a novel ATX inhibitor, PAT-048, on fibrosis and IL-6 expression in the mouse model of bleomycin-induced dermal fibrosis. We used dermal fibroblasts from SSc patients and control subjects to evaluate LPA-induced expression of IL-6, and IL-6-induced expression of ATX. We next evaluated whether LPA-induced ATX expression is dependent on IL-6, and whether baseline IL-6 expression in fibroblasts from SSc patients is dependent on ATX. Finally, we compared ATX and IL-6 expression in the skin of patients with SSc and healthy control subjects. RESULTS: PAT-048 markedly attenuated bleomycin-induced dermal fibrosis when treatment was initiated before or after the development of fibrosis. LPA stimulated expression of IL-6 in human dermal fibroblasts, and IL-6 stimulated fibroblast expression of ATX, connecting the ATX/LPA and IL-6 pathways in an amplification loop. IL-6 knockdown abrogated LPA-induced ATX expression in fibroblasts, and ATX inhibition attenuated IL-6 expression in fibroblasts and the skin of bleomycin-challenged mice. Expression of both ATX and IL-6 was increased in SSc skin, and LPA-induced IL-6 levels and IL-6-induced ATX levels were increased in fibroblasts from SSc patients compared with controls. CONCLUSION: ATX is required for the development and maintenance of dermal fibrosis in a mouse model of bleomycin-induced SSc and enables 2 major mediators of SSc fibrogenesis, LPA and IL-6, to amplify the production of each other. Our results suggest that concurrent inhibition of these 2 pathways may be an effective therapeutic strategy for dermal fibrosis in SSc. PMID- 27390296 TI - Poly Ethoxy Ethyl Glycinamide (PEE-G) Dendrimers: Dendrimers Specifically Designed for Pharmaceutical Applications. AB - Poly ethoxy ethyl glycinamide (PEE-G) dendrimers have been specifically designed and synthesized with the aim of providing a readily available dendrimer scaffold that can be used to make products that can meet the stringent requirements of pharmaceutical applications. The synthesis has been refined to produce dendrimers that are of high HPLC purity. The suitability of PEE-G dendrimers for their designed use has been verified by subsequent measurements to demonstrate that they are of high stability, high aqueous solubility, low cytotoxicity, low immunogenicity and with low in vivo toxicity in an escalating-dose rat study. PEE G dendrimers therefore provide a useful scaffold for researchers wanting to develop dendrimer-based drug candidates. PMID- 27390297 TI - Essential role of mitochondrial dynamics in muscle physiology. PMID- 27390298 TI - Exploring the capabilities of fluorometric online monitoring on chinese hamster ovary cell cultivations producing a monoclonal antibody. AB - Online monitoring of Chinese hamster ovary fed-batch cell cultures via two dimensional fluorescence spectroscopy (2DFS) was evaluated in this work. Particular attention was directed toward different process strategies regarding the use of nutrient-rich feed media and temperature shifts. These intentionally performed process manipulations broadened the variances in the obtained fluorescence spectra and this was suspected to hamper the generation of reliable soft sensors. Principal component analysis of the obtained fluorescence data showed that temperature shift and feeding strategy had a considerable impact on the fluorescence signals. Partial least square regression models were calculated for the prediction of glucose, lactate, monoclonal antibody (mAb), and viable cell concentrations (VCC). It was aimed to integrate all 2DFS datasets in the respective calibration models regardless of the process-strategy-dependent diversity. Contrary to the expectations, it was feasible to calibrate soft sensors for the online prediction of glucose (7 latent variables (LVs), Rcal2 = 0.97, rout mean squared error of prediction (RMSEP) = 1.1 g L-1 ), lactate (5 LV; Rcal2 = 0.96; RMSEP = 0.5 g L-1 ) and mAb concentrations (4 LV; Rcal2 = 0.99; RMSEP = 11.4 mg L-1 ). Feeding and temperature shifts had the highest impact on the VCC model (3 LV; Rcal2 = 0.94; RMSEP 3.8 * 105 mL-1 ), nevertheless the prediction of VCC from the fed-batch 2DFS data was feasible. The results strongly indicate that variances in the datasets due to the process strategy can be tolerated to some extent by the respective soft sensors. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1592-1600, 2016. PMID- 27390299 TI - Validation of Systemic Lupus Erythematosus Diagnosis as the Primary Cause of Renal Failure in the US Renal Data System. AB - OBJECTIVE: Using American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE) classification as gold standards, we determined sensitivity, specificity, positive and negative predictive values (PPV and NPV) of having SLE denoted as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). METHODS: ESRD patients were identified by International Classification of Diseases, Ninth Revision codes in electronic medical records of 1 large tertiary care center, Montefiore Hospital, from 2006 to 2012. Clinical data were extracted and reviewed to establish SLE diagnosis. Data were linked by social security number, name, and date of birth to the USRDS, where primary causes of ESRD were ascertained. RESULTS: Of 7,396 ESRD patients at Montefiore, 97 met ACR/SLICC SLE criteria, and 86 had SLE by record only. Among the 97 SLE patients, the attributed causes of ESRD in the USRDS were 77 SLE and 12 with other causes (unspecified glomerulonephritis, hypertension, scleroderma), and 8 missing. Sensitivity, specificity, PPV, and NPV for SLE in the USRDS were 79%, 99.9%, 93%, and 99.7%, respectively. Of the 60 patients with biopsy-proven lupus nephritis, 44 (73%) had SLE as primary ESRD cause in the USRDS. Attribution of the primary ESRD causes among SLE patients with ACR/SLICC criteria differed by race, ethnicity, and transplant status. CONCLUSION: The diagnosis of SLE as the primary cause of ESRD in the USRDS has good sensitivity, and excellent specificity, PPV, and NPV. Nationwide access to medical records and biopsy reports may significantly improve sensitivity of SLE diagnosis. PMID- 27390300 TI - Brief Report: Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia: A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis. AB - OBJECTIVE: We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM. METHODS: We prospectively evaluated 7 patients with DM and 7 patients with polymyositis (PM) for the detection of fasciitis with PDUS. MRI and PDUS were both performed in all patients. Fasciitis was histologically confirmed by en bloc biopsy. RESULTS: Among all patients with DM, 4 showed signs of fasciitis on MRI, while increased blood flow signals were observed along the fascia by PDUS in 6 DM patients, including 4 patients with early disease (<2 months after the onset of muscle symptoms). Histologically, significant fasciitis was confirmed in 4 patients with DM. In the remaining 3 patients with DM, significant fasciitis was not evident histologically, but mild proliferation of capillaries and mild inflammation were notable in the area of the fascia. Immunohistochemical staining for CD31 indicated abnormal neovascular proliferation in the fascia in patients with DM. None of the PM patients showed signs of fasciitis or increased vascularity by MRI, PDUS, or en bloc biopsy. CONCLUSION: In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM. PMID- 27390301 TI - Elevation of circulating serotonin improves calcium dynamics in the peripartum dairy cow. AB - Hypocalcemia is a metabolic disorder that affects dairy cows during the transition from pregnancy to lactation. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 days prepartum with either saline or 1.0mg/kg bodyweight of the immediate precursor to serotonin synthesis, 5hydroxy-l-tryptophan (5-HTP). On infusion days, blood was collected before, after, and at 2, 4, and 8h postinfusion. Blood and urine were collected daily before the infusion period, for 14 days postpartum and on day 30 postpartum. Milk was collected daily during the postpartum period. Feed intake and milk yield were unaffected by 5-HTP infusion postpartum. Cows infused with 5-HTP had elevated circulating serotonin concentrations prepartum. Infusion with 5-HTP induced a transient hypocalcemia in Jersey cows prepartum, but not in any other treatment. Holstein cows infused with saline had the highest milk calcium on the day of and day after parturition. Postpartum, circulating total calcium tended to be elevated, and urine deoxypyridinoline (DPD) concentrations were elevated in Holstein cows infused with 5-HTP. Overall, Jerseys had higher urine DPD concentrations postpartum when compared with Holsteins. Taken together, these data warrant further investigation of the potential therapeutic benefit of 5-HTP administration prepartum for prevention of hypocalcemia. Further research should focus on delineation of mechanisms associated with 5-HTP infusion that control calcium homeostasis during the peripartum period in Holstein and Jersey cows. PMID- 27390303 TI - Fukuoka criteria accurately predict risk for adverse outcomes during follow-up of pancreatic cysts presumed to be intraductal papillary mucinous neoplasms. AB - OBJECTIVE: Fukuoka consensus guidelines classify pancreatic cystic lesions (PCLs) presumed to be intraductal papillary mucinous neoplasms (IPMNs) into Fukuoka positive (FP) (subgroups of high-risk (HR) and worrisome features (WFs)) and Fukuoka negative (FN) (non-HR feature/WF cysts). We retrospectively estimated 5 year risk of pancreatic cancer (PC) in FN, WF and HR cysts of patients with PCL IPMN. DESIGN: From Mayo Clinic databases, we randomly selected 2000 patients reported to have a PCL; we excluded inflammatory or suspected non-IPMN cysts and those without imaging follow-up. We re-reviewed cross-sectional imaging and abstracted clinical and follow-up data on PCL-IPMNs. The study contained 802 patients with FN cysts and 358 with FP cysts. RESULTS: Patients with PCL-IPMN had median (IQR) follow-up of 4.2 (1.8-7.1) years. Among FN cysts, 5-year PC risk was low (2-3%) regardless of cyst size (p=0.67). After excluding events in the first 6 months, 5-year PC risk remained low (0-2%) regardless of cyst size (p=0.61). Among FP cysts, HR cysts (n=66) had greater 5-year PC risk than WF cysts (n=292) (49.7% vs 4.1%; p<0.001). In HR cysts, 3-year PC risk was greatest for obstructive jaundice versus enhancing solid component or main pancreatic duct >10 mm (79.8% vs 37.3% vs 39.4%, respectively; p=0.01). CONCLUSIONS: Fukuoka guidelines accurately stratify PCL-IPMNs for PC risk, with FN cysts having lowest and HR cysts having greatest risk. After 6-month follow-up, WF and FN cysts had a low 5-year PC risk. Surveillance strategies should be tailored appropriately. PMID- 27390304 TI - Diagnostic accuracy of the gamma-glutamyl transpeptidase to platelet ratio to predict liver fibrosis in Egyptian patients with HCV genotype 4. PMID- 27390306 TI - Walking the Talk. PMID- 27390307 TI - Comment on the Article "When Breast Milk Alone Is Not Enough: Barriers to Breastfeeding Continuation among Overweight and Obese Mothers". PMID- 27390305 TI - A prospective randomised trial of LigaSure Small Jaw(r) versus conventional neck dissection in head and neck cancer patients. AB - OBJECTIVES: We compared the differences between LigaSure Small Jaw(r)-assisted and conventional neck dissection in patients with head and neck cancer. DESIGN: Prospective randomised study. SETTING: Tertiary referral hospital. PARTICIPANTS: Patients scheduled to undergo neck dissection due to head and neck cancer were eligible for this study. The study group was treated using the LigaSure vessel sealing system (Small Jaw(r); Covidien, Colorado, USA) for dissection and hemostasis throughout the whole procedures (ClinicalTrials.gov number: NCT02597582). MAIN OUTCOMES MEASURES: Operation duration, perioperative blood loss, postoperative drainage amount and postoperative pain status. RESULTS: The study group consisted of 21 patients, while the control group had 20 patients. The operation duration was shorter (97.1 versus 116.3 min, P = 0.022) and the average amount of injected analgesics was lower (8.8 versus 17.7 ampules, P = 0.037) in the study group. CONCLUSIONS: The assistance of the LigaSure Small Jaw(r) during functional neck dissection shortened the operation duration and decreased the amount of injected analgesics needed. PMID- 27390302 TI - Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish. AB - Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia treated embryos showed delayed physical development (slower hatching and straightening of head-trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone programmed fish appeared 'bolder' than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and development in the zebrafish and that, like other species, manipulating GC status pharmacologically, physiologically or genetically in early life leads to programmable metabolic and behavioural traits in adulthood. PMID- 27390310 TI - Severe Health-Related Quality of Life Impairment in Active Primary Sjogren's Syndrome and Patient-Reported Outcomes: Data From a Large Therapeutic Trial. AB - OBJECTIVE: To identify the principal determinants of health-related quality of life (HRQOL) impairment in patients with active primary Sjogren's syndrome (SS) participating in a large therapeutic trial, Tolerance and Efficacy of Rituximab in Primary Sjogren's Syndrome (TEARS). METHODS: At the inclusion visit for the TEARS trial, 120 patients with active primary SS completed the Short Form 36 health survey (SF-36), a validated HRQOL assessment tool. Univariate then multivariate linear regression analyses were used to assess associations linking SF-36 physical and mental components to demographic data, patient-reported outcomes (symptom intensity assessments for dryness, pain, and fatigue, including the European League Against Rheumatism [EULAR] Sjogren's Syndrome Patient Reported Index [ESSPRI]), objective measures of dryness and autoimmunity, and physician evaluation of systemic activity (using the EULAR Sjogren's Syndrome Disease Activity Index [ESSDAI]). RESULTS: SF-36 scores indicated marked HRQOL impairments in our population with active primary SS. Approximately one-third of the patients had low, moderate, and high systemic activity according to the ESSDAI. ESSPRI and ESSDAI scores were moderately but significantly correlated. The factors most strongly associated with HRQOL impairment were patient-reported symptoms, best assessed using the ESSPRI, with pain and ocular dryness intensity showing independent associations with HRQOL. Conversely, systemic activity level was not associated with HRQOL impairment in multivariate analyses, even in the patient subset with ESSDAI values indicating moderate-to-high systemic activity. CONCLUSION: The cardinal symptoms of primary SS (dryness, pain, and fatigue, best assessed using the ESSPRI) are stronger predictors of HRQOL impairment than systemic involvement (assessed by the ESSDAI) and should be used as end points in future therapeutic trials focusing on patients' well-being. New consensual and data-driven response criteria are needed for primary SS studies. PMID- 27390311 TI - Expressions of isopeptide bonds and corneodesmosin in middle ear cholesteatoma. AB - OBJECTIVE: Isopeptide bonds form cross-links between constituent proteins in the horny layer of the epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes, which bind corneocytes together. Both play important roles in maintaining epidermal barrier functions. In the present study, we investigated the expressions of isopeptide bonds, CDSN, and related enzymes in middle ear cholesteatoma in comparison with the skin. DESIGN: Prospective case series of patients with middle ear cholesteatoma. SETTING: Tertiary medical institute. PARTICIPANTS: Cholesteatoma and normal postauricular skin were collected from patients with acquired middle ear cholesteatoma during tympanomastoidectomy. MAIN OUTCOME MEASURES: Expression of e-(g-glutamyl)lysine isopeptide bonds was examined by immunohistochemistry; Expressions of transglutaminase (TGase)1, TGase2, TGase3, and TGase5 by immunohistochemistry and quantitative RT-PCR (qRT PCR); expression of CDSN by immunohistochemistry, qRT-PCR, and Western blot; and expressions of tissue kallikrein-related peptidase (KLK)5, KLK7, KLK14, and serine peptidase inhibitor Kazal type 5 (SPINK5) by qRT-PCR. RESULTS: TGase2 was higher (P=0.0046) and TGase5 was lower (P=0.0008) in cholesteatoma than in the postauricular skin. Immunoreactivity for isopeptide bonds was localized in the granular and horny layers, and was not different between the two tissues. Immunoreactivity for CDSN was localized in the granular layer, and was lower in cholesteatoma than in the skin (P=0.0090). Western blot and qRT-PCR confirmed that the expression of CDSN was lower in cholesteatoma than in the skin. Expressions of KLK5, KLK7, KLK14, or SPINK5 were not different between the two tissues. CONCLUSIONS: These results indicate that the production of CDSN is likely to be suppressed in cholesteatoma, which would account, at least in part, for the mechanical fragility and increased permeability of the cholesteatoma epithelium. PMID- 27390313 TI - Dorsal Lumbar Disc Migrations with Lateral and Ventral Epidural Extension on Axial MRI: A Case Series and Review of the Literature. AB - Dorsal epidural migration of lumbar disc extrusion is rare and commonly misdiagnosed. Our purpose was to retrospectively analyze soft-tissue abnormalities on axial MR imaging in both the ventral and lateral epidural space in such dorsal epidural migrations. The presence of each component required complete concordance by 3 independent neuroradiologist readers. In a case series (n = 6) of surgically proved dorsal lumbar disc migrations, in which the radiologist's favored prospective diagnosis had not been correct, each case demonstrated epidural soft-tissue abnormality that had components both laterally and ventrally, abutting the parent disc. Similarly, in previously published cases for which axial MR imaging was available, the lateral component was demonstrated in 23/24 cases (96%). Ventral abutment of the parent disc was evident, in addition, in 17/18 cases (94%) with available disc-level axial images. Both ventral and lateral epidural soft-tissue abnormalities are typically present in dorsal lumbar disc herniations and may help radiologists suggest this rare diagnosis in appropriate cases. PMID- 27390312 TI - Value of History, Physical Examination, and Radiographic Findings in the Diagnosis of Symptomatic Meniscal Tear Among Middle-Aged Subjects With Knee Pain. AB - OBJECTIVE: To evaluate the utility of clinical history, radiographic findings, and physical examination findings in the diagnosis of symptomatic meniscal tear (SMT) in patients over age 45 years, in whom concomitant osteoarthritis is prevalent. METHODS: In a cross-sectional study of patients from 2 orthopedic surgeons' clinics, we assessed clinical history, physical examination findings, and radiographic findings in patients age >45 years with knee pain. The orthopedic surgeons rated their confidence that subjects' symptoms were due to meniscal tear; we defined the diagnosis of SMT as at least 70% confidence. We used logistic regression to identify factors independently associated with diagnosis of SMT, and we used the regression results to construct an index of the likelihood of SMT. RESULTS: In 174 participants, 6 findings were associated independently with the expert clinician having >=70% confidence that symptoms were due to meniscal tear: localized pain, ability to fully bend the knee, pain duration <1 year, lack of varus alignment, lack of pes planus, and absence of joint space narrowing on radiographs. The index identified a low-risk group with 3% likelihood of SMT. CONCLUSION: While clinicians traditionally rely upon mechanical symptoms in this diagnostic setting, our findings did not support the conclusion that mechanical symptoms were associated with the expert's confidence that symptoms were due to meniscal tear. An index that includes history of localized pain, full flexion, duration <1 year, pes planus, varus alignment, and joint space narrowing can be used to stratify patients according to their risk of SMT, and it identifies a subgroup with very low risk. PMID- 27390314 TI - Geographic Differences in Endovascular Treatment and Retreatment of Cerebral Aneurysms. AB - BACKGROUND AND PURPOSE: Comparing outcomes between endovascular aneurysm coiling trials can be difficult because of heterogeneity in patients and end points. We sought to understand the impact of geography on aneurysm retreatment in patients enrolled in the Matrix and Platinum Science Trial. MATERIALS AND METHODS: Post hoc analysis was performed on data from the Matrix and Platinum Science trial. Patients were stratified as either North American or international. Baseline patient demographics, comorbidities, aneurysm characteristics, procedural complications, and clinical and angiographic outcomes were compared. RESULTS: We evaluated 407 patients from 28 North American sites and 219 patients from 15 international sites. Patient demographics differed significantly between North American and international sites. Aneurysms were well occluded postprocedure more often at international than North American sites (P < .001). Stents were used significantly more often at North American sites (32.7% [133 of 407]) compared with international sites (10.0% [22 of 219]; P < .001). At 455 days, there was no difference in the proportion of patients alive and free of disability (P = .56) or with residual aneurysm filling (P = .10). Ruptured aneurysms were significantly more likely to have been retreated at North American sites within the first year (P < .001) and at 2 years (P < .001). Among all patients for whom the treating physician believed there to be Raymond 3 aneurysm filling at follow up, absolute rates of retreatment at international and North American sites were similar by 2-year follow-up. CONCLUSIONS: Data from the Matrix and Platinum Science Trial demonstrate that aneurysm retreatment occurs with different frequency and at different times in different regions of the world. This trend has critical value when interpreting trials reporting short-term outcomes, especially when judgment-based metrics such as retreatment are primary end points that may or may not take place within the defined study follow-up period. Though these variations can be controlled for and balanced within a given randomized trial, such differences in practice patterns must be accounted for in any attempt to compare outcomes between different trials. Despite these differences, endovascular-treated intracranial aneurysms around the world have similar clinical outcomes. PMID- 27390315 TI - CT Fluoroscopy-Guided Blood Patching of Ventral CSF Leaks by Direct Needle Placement in the Ventral Epidural Space Using a Transforaminal Approach. AB - BACKGROUND AND PURPOSE: Epidural blood patch treatment of spontaneous intracranial hypotension arising from ventral CSF leaks can be difficult secondary to challenges in achieving ventral spread of patching material. The purpose of this study was to determine the technical success rates and safety profile of direct needle placement into the ventral epidural space via a posterior transforaminal approach. MATERIALS AND METHODS: We retrospectively reviewed consecutive CT fluoroscopy-guided epidural blood patches from June 2013 through July 2015. Cases were included if a posterior transforaminal approach was taken to place the needle directly in the ventral epidural space. Rates of technical success (defined as contrast in the spinal canal ventral epidural space) and optimal epidurogram (defined as contrast spreading into or beyond the middle third of the spinal canal ventral epidural space) were determined. Factors influencing these rates were assessed. All complications, inadvertent intravascular injections, and intrathecal punctures were recorded. RESULTS: A total of 72 ventral epidural blood patches were identified; immediate technical success was achieved in 95.8% and an optimal epidurogram in 47.2%. Needle position within the spinal canal ventral epidural space was associated with obtaining an optimal epidurogram (P = .005). Inadvertent intravascular injection was identified in 29.3% of cases, but all were venous. There were no inadvertent intrathecal punctures or complications. CONCLUSIONS: Direct needle placement in the ventral epidural space via a transforaminal approach for treatment of ventral CSF leaks has an excellent technical success rate and safety profile. This technique can be considered as a treatment option in selected patients with ventral CSF leaks for whom traditional techniques are unsuccessful. PMID- 27390317 TI - 3D MR Neurography of the Lumbosacral Plexus: Obtaining Optimal Images for Selective Longitudinal Nerve Depiction. AB - BACKGROUND AND PURPOSE: The number of centers currently performing 3D fat suppressed isotropic imaging is limited. If the angular orientations of the major lumbosacral plexus nerves on 3D isotropic MR neurography could be determined, similar planes could be prescribed during acquisition of 2D or 3D nonisotropic techniques for optimal depiction of various nerves. Our aim was to determine oblique sagittal and coronal angular measurements for longitudinal depiction of lumbosacral plexus nerves. Interobserver and intraobserver performance and mean calibers of sciatic and femoral nerves were also determined. MATERIALS AND METHODS: A consecutive series of lumbosacral plexus MR neurography examinations with 3D nerve-selective imaging performed during a 10-month period on a 3T scanner were evaluated. Two observers performed reconstructions and angular measurements. Sciatic and femoral nerve diameters were measured. Descriptive statistics and intraclass correlation coefficient correlations were used. RESULTS: There were 52 subjects, 11 men and 41 women. Mean sagittal thecal sac angles for coronal demonstration of lumbosacral plexus nerve roots from L1 to S1 for 2 independent observers measured 13.58 degrees +/- 2.87 degrees and 13.61 degrees +/- 2.18 degrees . Mean sagittal femoral nerve angles were 27.78 degrees +/- 4.81 degrees and 28.94 degrees +/- 4.49 degrees , and mean sagittal sciatic nerve angles were -10.7 degrees +/- 3.75 degrees and -11.82 degrees +/ 2.87 degrees . Coronal angular measurements of the femoral and sciatic nerves were similar. The intraclass correlation coefficient was moderate (0.582-0.671) for interobserver performance. For intraobserver performance among various angular measurements, the intraclass correlation coefficient was moderate to good (0.586-0.788). Femoral nerve caliber on MR imaging was almost half that of the sciatic nerve. Mean right femoral nerve thickness was 4.52 +/- 1.11 mm and 4.85 +/- 0.64 mm for the 2 observers, and mean left femoral nerve thickness was 4.48 +/- 0.97 mm and 4.94 +/- 0.57 mm. Mean right sciatic nerve thickness was 9.71 +/- 1.76 mm and 9.94 +/- 0.83 mm, and mean left sciatic nerve thickness was 10.03 +/- 1.71 mm and 9.98 +/- 0.99 mm. CONCLUSIONS: Angular lumbosacral plexus measurements aid in the prescription of different planes on MR imaging for the optimal longitudinal demonstration of nerves. PMID- 27390318 TI - Diffusion-Weighted Imaging for Predicting and Monitoring Primary Central Nervous System Lymphoma Treatment Response. AB - BACKGROUND AND PURPOSE: Whether ADC value predicts the therapy response and outcomes of primary central system lymphoma remains controversial. This study assessed the minimum ADC correlated with treatment response in patients with primary central nervous system lymphoma undergoing methotrexate-based chemotherapy. MATERIALS AND METHODS: Thirty-five patients with primary central nervous system lymphoma underwent conventional MR imaging and DWI before chemotherapy and after 1 and 5 cycles of chemotherapy. Treatment response was determined according to the International PCNSL Collaborative Group criteria and was classified as a complete response, partial response, or progressive disease. Pretreatment minimum ADC, minimum ADC after 1 cycle, minimum ADC after 5 cycles, and change in minimum ADC were compared among the different response groups. The Pearson correlation test was calculated between these ADC parameters and tumor response. RESULTS: The pretreatment minimum ADC of the progressive disease group was lower than that of the complete response and partial response groups, but there was no significant difference among them. The minimum ADC after 1 cycle and minimum ADC after 5 cycles were statistically significantly higher than the pretreatment minimum ADC. A comparison among groups showed that minimum ADC after 1 cycle, minimum ADC after 5 cycles, minimum ADC change, and the percentage of minimum ADC change were all significantly different among the 3 groups. A significant positive correlation was observed between the percentage of minimum ADC after 1 cycle of chemotherapy and the size reduction percentage after 5 cycles of chemotherapy. The minimum ADC change and the percentage of minimum ADC change performed better in the differentiation of the final treatment response, specifically in complete response and partial response from progressive disease. CONCLUSIONS: The minimum ADC after 1 cycle and minimum ADC changes were better correlated with the treatment response than the pretreatment minimum ADC. Minimum ADC after early therapy may potentially to be used to predict and monitor the response of primary central nervous system lymphoma to chemotherapy. PMID- 27390316 TI - Porcine In Vivo Validation of a Virtual Contrast Model: The Influence of Contrast Agent Properties and Vessel Flow Rates. AB - BACKGROUND AND PURPOSE: Accurately and efficiently modeling the transport of angiographic contrast currently offers the best method of verifying computational fluid dynamics simulations and, with it, progress toward the lofty goal of prediction of aneurysm treatment outcome a priori. This study specifically examines the influence of estimated flow rate and contrast properties on such in silico predictions of aneurysm contrast residence and decay. MATERIALS AND METHODS: Four experimental sidewall aneurysms were created in swine, with aneurysm contrast flow patterns and decay rates observed under angiography. A simplified computational fluid dynamics model of the experimental aneurysm was constructed from 3D angiography and contrast residence predicted a priori. The relative influence of a number of estimated model parameters (contrast viscosity, contrast density, and blood flow rate) on contrast residence was then investigated with further simulations. RESULTS: Contrast infiltration and washout pattern were accurately predicted by the a priori computational fluid dynamics model; however, the contrast decay rate was underestimated by ~25%. This error was attributed to the estimated parent vessel flow rate alone, and the effects of contrast viscosity and density on the decay rate were found to be inconsequential. A linear correlation between the parent vessel flow rate and the corresponding contrast decay rate was observed. CONCLUSIONS: In experimental sidewall aneurysms, contrast fluid properties (viscosity and density) were shown to have a negligible effect on variation in the modeled contrast decay rate. A strong linear correlation was observed between parent vessel flow rate and contrast decay over a physiologically reasonable range of flow rates. PMID- 27390319 TI - Wall Apposition Is a Key Factor for Aneurysm Occlusion after Flow Diversion: A Histologic Evaluation in 41 Rabbits. AB - BACKGROUND AND PURPOSE: Robust wall apposition for flow-diverter stents may be important for endothelialization. Using a large series of experimental aneurysms treated with the Pipeline Embolization Device, the objectives of this study were to 1) assess interobserver agreement for the evaluation of wall apposition on posttreatment DSA and evaluate its association with aneurysm occlusion, and 2) measure the relationship between wall apposition assessed with histology and aneurysm occlusion rate after treatment. MATERIALS AND METHODS: Saccular aneurysms were created in 41 rabbits and treated with the Pipeline Embolization Device. DSA was performed just after the deployment of the device and at follow up. Three investigators independently graded wall apposition on posttreatment DSA as good or poor. A histopathologist blinded to the angiographic results graded the wall apposition on histologic samples. We examined the correlation between angiographic occlusion and wall apposition with histology and angiography. RESULTS: Wall apposition evaluated on histology was strongly associated with saccular aneurysm occlusion. Sensitivity and specificity of wall apposition to predict complete occlusion at follow-up were 76.9% and 84.0%, respectively, with an overall accuracy of 81.6%. In this experimental study, DSA was suboptimal to assess flow-diverter apposition, with moderate interobserver agreement and low accuracy. CONCLUSIONS: Good wall apposition is strongly associated with complete occlusion after flow-diverter therapy. In this study, DSA was suboptimal for assessing wall apposition of flow-diverter stents. These findings suggest that improved tools for assessing flow diverter-stent wall apposition are highly relevant. PMID- 27390320 TI - Prophylactic Antiplatelet Medication in Endovascular Treatment of Intracranial Aneurysms: Low-Dose Prasugrel versus Clopidogrel. AB - BACKGROUND AND PURPOSE: Prophylactic antiplatelet medication is beneficial in decreasing thromboembolic complications during endovascular treatment of unruptured intracranial aneurysms. The efficacy may be limited by variability of individual response to antiplatelet medication, especially clopidogrel. We compared the efficacy of 2 antiplatelet medications, low-dose prasugrel and clopidogrel, in patients undergoing endovascular treatment of unruptured aneurysms. MATERIALS AND METHODS: From November 2014 to July 2015, 194 patients with a total of 222 unruptured aneurysms underwent endovascular treatment at a single institution. Laboratory and clinical data from the prospectively maintained registry were used in this study. Antiplatelet medication was given the day before endovascular treatment (prasugrel 20 mg or 30 mg or clopidogrel 300 mg). Response to the antiplatelet medication was measured by the VerifyNow system. Periprocedural adverse event rates between the 2 groups were compared. RESULTS: There were no significant differences in the baseline characteristics of patients and aneurysms between the 2 groups. The P2Y12 reaction unit values were lower (clopidogrel group versus prasugrel group, 242.7 +/- 69.8 vs 125.7 +/- 79.4; P < .0001) and percentage inhibition values were higher (22.1% +/- 19.7% vs 60.2 +/- 24.7%; P < .0001) in the prasugrel group. There were no thromboembolic events, but there was 1 procedural bleed in each group, without any clinical consequences. CONCLUSIONS: The prasugrel group showed more effective and consistent platelet inhibition. We may omit the antiplatelet response assay with the low-dose prasugrel premedication before the endovascular treatment of patients with unruptured aneurysms. Further study is required to determine whether there is benefit of this strategy regarding clinical outcome. PMID- 27390321 TI - Early Biomarkers from Conventional and Delayed-Contrast MRI to Predict the Response to Bevacizumab in Recurrent High-Grade Gliomas. AB - BACKGROUND AND PURPOSE: The interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab. MATERIALS AND METHODS: Twenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment by standard and delayed-contrast MR imaging. The mean change in lesion volumes of responders (overall survival, >=1 year) and nonresponders (overall survival, <1 year) was studied. The lesion volumes at baseline and the changes in lesion volumes 1 month after treatment initiation, calculated from standard and delayed-contrast MRIs, were studied as possible predictors of outcome. In scans acquired at progression, the average change in lesion volume from previous follow-up in standard and delayed-contrast MRIs was compared. RESULTS: Response and progression patterns were identified from the mean change in lesion volumes, depicted from conventional T1WI, delayed contrast enhanced MR imaging, and DSC MR imaging. Thresholds for early prediction of response were calculated by using these sequences. For each predictor, sensitivity, specificity, positive predictive values, and negative predictive values were calculated, reaching 85.7%, 87.5%, 75%, and 93.3% for conventional T1WI; 100%, 87.5%, 77.8%, and 100% for delayed-contrast MR imaging; and 75%, 78.6%, 50%, and 91.7% for DSC MR imaging. The benefit of delayed-contrast MR imaging in separating responders and nonresponders was further confirmed by using log-rank tests (conventional T1WI, P = .0022; delayed-contrast MR imaging, P < .0001; DSC MR imaging, P = .0232) and receiver operating characteristic analyses. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI (P < .01); these findings suggest that progression may be depicted more effectively in treatment-response assessment maps. CONCLUSIONS: The benefit of contrast-enhanced MR imaging for assessing and predicting the response to bevacizumab was demonstrated. The increased sensitivity of the treatment-response-assessment maps reflects their potential contribution to the management of bevacizumab-treated patients with recurrent high-grade glioma. PMID- 27390322 TI - Imaging Appearance of SMARCB1 (INI1)-Deficient Sinonasal Carcinoma: A Newly Described Sinonasal Malignancy. AB - SMARCB1 (INI1)-deficient sinonasal carcinomas were first described in 2014, and this series of 17 cases represents the first imaging description. This tumor is part of a larger group of SMARCB1-deficient neoplasms, characterized by aggressive behavior and a rhabdoid cytopathologic appearance, that affect multiple anatomic sites. Clinical and imaging features overlap considerably with other aggressive sinonasal malignancies such as sinonasal undifferentiated carcinoma, which represents a common initial pathologic diagnosis in this entity. SMARCB1 (INI1)-deficient sinonasal tumors occurred most frequently in the nasoethmoidal region with invasion of the adjacent orbit and anterior cranial fossa. Avid contrast enhancement, intermediate to low T2 signal, and FDG avidity were frequent imaging features. Approximately half of the lesions demonstrated calcification, some with an unusual "hair on end" appearance, suggesting aggressive periosteal reaction. PMID- 27390323 TI - A Kaleidoscope of Hope: Exploring Experiences of Hope Among Service Users and Informal Carers in Health Care Contexts. AB - BACKGROUND: There is a large and diverse literature on the concept of hope in health care. This literature covers a broad spectrum of perspectives, from philosophical, conceptual, and theoretical analysis through to attempts at measuring the concept of hope with differing health care users. AIMS: To explore the concept of hope through the secondary analysis of existing data sets, with the intention of understanding hope in the context of person-centeredness. RESEARCH QUESTION: What is the experience of hope among service users and informal carers in different health care contexts? METHOD: Secondary analysis of data derived from three research studies. FINDINGS: We identified four key themes that together illustrate what we describe as a kaleidoscope of hope, reinforcing the view that there is no one presentation of hope and that practitioners must engage authentically with service users to determine the most effective and appropriate intervention strategies. CONCLUSIONS: Hope is not a singular phenomenon, and in the context of person-centered practice there is a need for practitioners to engage authentically with service users and listen carefully to what may bring hope for them. PMID- 27390325 TI - Retraction. PMID- 27390324 TI - Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse. AB - Divalent metal-ion transporter-1 (DMT1), the principal mechanism by which nonheme iron is taken up at the intestinal brush border, is energized by the H(+) electrochemical potential gradient. The provenance of the H(+) gradient in vivo is unknown, so we have explored a role for brush-border Na(+)/H(+) exchanger (NHE) isoforms by examining iron homeostasis and intestinal iron handling in mice lacking NHE2 or NHE3. We observed modestly depleted liver iron stores in NHE2 null (NHE2(-/-)) mice stressed on a low-iron diet but no change in hematological or blood iron variables or the expression of genes associated with iron metabolism compared with wild-type mice. Ablation of NHE3 strongly depleted liver iron stores, regardless of diet. We observed decreases in blood iron variables but no overt anemia in NHE3-null (NHE3(-/-)) mice on a low-iron diet. Intestinal expression of DMT1, the apical surface ferrireductase cytochrome b reductase-1, and the basolateral iron exporter ferroportin was upregulated in NHE3(-/-) mice, and expression of liver Hamp1 (hepcidin) was suppressed compared with wild-type mice. Absorption of (59)Fe from an oral dose was substantially impaired in NHE3( /-) compared with wild-type mice. Our data point to an important role for NHE3 in generating the H(+) gradient that drives DMT1-mediated iron uptake at the intestinal brush border. PMID- 27390326 TI - New Member of Endothelial Arsenal Against Inflammation. PMID- 27390327 TI - A Janus-Faced Role for Atrial Natriuretic Peptide in Myocardial Infarction? PMID- 27390328 TI - COMP-lex Mechanics: Matricrine Signaling. PMID- 27390329 TI - A Case of Sudden Death in Decameron IV.6: Aortic Dissection or Atrial Myxoma? AB - Giovanni Boccaccio's Decameron contains a novella that details the sudden death of a young man called Gabriotto, including a portrayal of the discomfort that the protagonist experienced and a rudimentary autopsy performed by local physicians. The intriguing description of symptoms and pathologies has made it possible to read a 7-century-old case through the modern clinical lens. Thanks to the medical and philological analysis of the text-despite the vast difference between modern and medieval medicine-2 hypothetical diagnoses have emerged: either an aortic dissection or an atrial myxoma. PMID- 27390330 TI - Does Elevated Glucose Promote Atherosclerosis? Pros and Cons. PMID- 27390331 TI - Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance? AB - Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible. PMID- 27390332 TI - T1 Mapping in Characterizing Myocardial Disease: A Comprehensive Review. AB - Cardiovascular magnetic resonance provides insights into myocardial structure and function noninvasively, with high diagnostic accuracy and without ionizing radiation. Myocardial tissue characterization in particular gives cardiovascular magnetic resonance a prime role among all the noninvasive cardiovascular investigations. Late gadolinium enhancement imaging is an established method for visualizing replacement scar, providing diagnostic and prognostic information in a variety of cardiac conditions. Late gadolinium enhancement, however, relies on the regional segregation of tissue characteristics to generate the imaging contrast. Thus, myocardial pathology that is diffuse in nature and affecting the myocardium in a rather uniform and global distribution is not well visualized with late gadolinium enhancement. Examples include diffuse myocardial inflammation, fibrosis, hypertrophy, and infiltration. T1 mapping is a novel technique allowing to diagnose these diffuse conditions by measurement of T1 values, which directly correspond to variation in intrinsic myocardial tissue properties. In addition to providing clinically meaningful indices, T1-mapping measurements also allow for an estimation of extracellular space by calculation of extracellular volume fraction. Multiple lines of evidence suggest a central role for T1 mapping in detection of diffuse myocardial disease in early disease stages and complements late gadolinium enhancement in visualization of the regional changes in common advanced myocardial disease. As a quantifiable measure, it may allow grading of disease activity, monitoring progress, and guiding treatment, potentially as a fast contrast-free clinical application. We present an overview of clinically relevant technical aspects of acquisition and processing, and the current state of art and evidence, supporting its clinical use. PMID- 27390333 TI - Fractional Flow Reserve and Coronary Computed Tomographic Angiography: A Review and Critical Analysis. AB - Invasive fractional flow reserve (FFR) is now the gold standard for intervention. Noninvasive functional imaging analyses derived from coronary computed tomographic angiography (CTA) offer alternatives for evaluating lesion-specific ischemia. CT-FFR, CT myocardial perfusion imaging, and transluminal attenuation gradient/corrected contrast opacification have been studied using invasive FFR as the gold standard. CT-FFR has demonstrated significant improvement in specificity and positive predictive value compared with CTA alone for predicting FFR of <=0.80, as well as decreasing the frequency of nonobstructive invasive coronary angiography. High-risk plaque characteristics have also been strongly implicated in abnormal FFR. Myocardial computed tomographic perfusion is an alternative method with promising results; it involves more radiation and contrast. Transluminal attenuation gradient/corrected contrast opacification is more controversial and may be more related to vessel diameter than stenosis. Important considerations remain: (1) improvement of CTA quality to decrease unevaluable studies, (2) is the diagnostic accuracy of CT-FFR sufficient? (3) can CT-FFR guide intervention without invasive FFR confirmation? (4) what are the long-term outcomes of CT-FFR-guided treatment and how do they compare with other functional imaging-guided paradigms? (5) what degree of stenosis on CTA warrants CT-FFR? (6) how should high-risk plaque be incorporated into treatment decisions? (7) how will CT-FFR influence other functional imaging test utilization, and what will be the effect on the practice of cardiology? (8) will a workstation-based CT-FFR be mandatory? Rapid progress to date suggests that CTA-based lesion-specific ischemia will be the gatekeeper to the cardiac catheterization laboratory and will transform the world of intervention. PMID- 27390334 TI - Prognostic Determinants of Coronary Atherosclerosis in Stable Ischemic Heart Disease: Anatomy, Physiology, or Morphology? AB - Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease. PMID- 27390336 TI - Transcathether Valve Replacement and Valve Repair: Review of Procedures and Intraprocedural Echocardiographic Imaging. AB - Transcatheter aortic valve replacement for treatment of aortic stenosis has now become an accepted alternative to surgical valve replacement for some patients. In addition, transcatheter mitral valve repair is also routinely used in high surgical risk patients with mitral regurgitation. Other transcatheter procedures are in rapid development. The current review attempts to summarize the procedures and echocardiographic imaging used for transcatheter valve replacement or valve repair. PMID- 27390337 TI - Advances in Echocardiographic Imaging in Heart Failure With Reduced and Preserved Ejection Fraction. AB - Echocardiography, given its safety, easy availability, and the ability to permit a comprehensive assessment of cardiac structure and function, is an indispensable tool in the evaluation and management of patients with heart failure (HF). From initial phenotyping and risk stratification to providing vital data for guiding therapeutic decision-making and monitoring, echocardiography plays a pivotal role in the care of HF patients. The recent advent of multiparametric approaches for myocardial deformation imaging has provided valuable insights in the pathogenesis of HF, elucidating distinct patterns of myocardial dysfunction and events that are associated with progression from subclinical stage to overt HF. At the same time, miniaturization of echocardiography has further expanded clinical application of echocardiography, with the use of pocket cardiac ultrasound as an adjunct to physical examination demonstrated to improve diagnostic accuracy and risk stratification. Furthermore, ongoing advances in the field of big data analytics promise to create an exciting opportunity to operationalize precision medicine as the new approach to healthcare delivery that aims to individualize patient care by integrating data extracted from clinical, laboratory, echocardiographic, and genetic assessments. The present review summarizes the recent advances in the field of echocardiography, with emphasis on their role in HF phenotyping, risk stratification, and optimizing clinical outcomes. PMID- 27390335 TI - Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis. AB - Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques. PMID- 27390338 TI - Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator. AB - Endothelial cells control vascular tone by releasing nitric oxide (NO) produced by endothelial NO synthase. The activity of endothelial NO synthase is modulated by the calcium concentration and by post-translational modifications (eg, phosphorylation). When NO reaches vascular smooth muscle, soluble guanylyl cyclase is its primary target producing cGMP. NO production is stimulated by circulating substances (eg, catecholamines), platelet products (eg, serotonin), autacoids formed in (eg, bradykinin) or near (eg, adiponectin) the vascular wall and physical factors (eg, shear stress). NO dysfunction can be caused, alone or in combination, by abnormal coupling of endothelial cell membrane receptors, insufficient supply of substrate (l-arginine) or cofactors (tetrahydrobiopterin), endogenous inhibitors (asymmetrical dimethyl arginine), reduced expression/presence/dimerization of endothelial NO synthase, inhibition of its enzymatic activity, accelerated disposition of NO by reactive oxygen species and abnormal responses (eg, biased soluble guanylyl cyclase activity producing cyclic inosine monophosphate) of the vascular smooth muscle. Major culprits causing endothelial dysfunction, irrespective of the underlying pathological process (aging, obesity, diabetes mellitus, and hypertension), include stimulation of mineralocorticoid receptors, activation of endothelial Rho-kinase, augmented presence of asymmetrical dimethyl arginine, and exaggerated oxidative stress. Genetic and pharmacological interventions improve dysfunctional NO-mediated vasodilatations if protecting the supply of substrate and cofactors for endothelial NO synthase, preserving the presence and activity of the enzyme and reducing reactive oxygen species generation. Common achievers of such improvement include maintained levels of estrogens and increased production of adiponectin and induction of silent mating-type information regulation 2 homologue 1. Obviously, endothelium-dependent relaxations are not the only beneficial action of NO in the vascular wall. Thus, reduced NO-mediated responses precede and initiate the atherosclerotic process. PMID- 27390339 TI - Letter by Karlstaedt and Taegtmeyer Regarding Article, "Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy". PMID- 27390340 TI - Response by Zhou et al to Letter Regarding Article, "Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy". PMID- 27390341 TI - Letter by Marlicz et al Regarding Article, "Proton Pump Inhibitors Accelerate Endothelial Senescence". PMID- 27390342 TI - Cotargeting HSP90 and Its Client Proteins for Treatment of Prostate Cancer. AB - Castration-resistant prostate cancer (CRPC) is the later stage of prostate cancer when the disease has stopped responding to androgen deprivation therapy (ADT). It has been established that androgen receptor (AR) reactivation is responsible for the recurrence of prostate cancer after ADT. Thus, targeting different pathways that regulate AR stability and activity should be a promising strategy for treatment of CRPC. Heat shock proteins (HSP) are chaperones that modify stability and activity of their client proteins. HSP90, a major player in the HSP family, regulates stability of many proteins, including AR and Polo-like kinase 1 (Plk1), a critical regulator of many cell-cycle events. Further, HSP90 is overexpressed in different cancers, including prostate cancer. Herein, we show that cotreatment of prostate cancer with AR antagonist enzalutamide and HSP90 inhibitor leads to more severe cell death due to a synergistic reduction of AR protein. Interestingly, we show that overexpression of Plk1 rescued the synergistic effect and that cotargeting HSP90 and Plk1 also leads to more severe cell death. Mechanistically, we show that E3 ligase CHIP, in addition to targeting AR, is responsible for the degradation of Plk1 as well. These findings suggest that cotargeting HSP90 and some of its client proteins may be a useful strategy in treatment of CRPC. Mol Cancer Ther; 15(9); 2107-18. (c)2016 AACR. PMID- 27390343 TI - Direct Pharmacological Inhibition of beta-Catenin by RNA Interference in Tumors of Diverse Origin. AB - The Wnt/beta-catenin pathway is among the most frequently altered signaling networks in human cancers. Despite decades of preclinical and clinical research, efficient therapeutic targeting of Wnt/beta-catenin has been elusive. RNA interference (RNAi) technology silences genes at the mRNA level and therefore can be applied to previously undruggable targets. Lipid nanoparticles (LNP) represent an elegant solution for the delivery of RNAi-triggering oligonucleotides to disease-relevant tissues, but have been mostly restricted to applications in the liver. In this study, we systematically tuned the composition of a prototype LNP to enable tumor-selective delivery of a Dicer-substrate siRNA (DsiRNA) targeting CTNNB1, the gene encoding beta-catenin. This formulation, termed EnCore-R, demonstrated pharmacodynamic activity in subcutaneous human tumor xenografts, orthotopic patient-derived xenograft (PDX) tumors, disseminated hematopoietic tumors, genetically induced primary liver tumors, metastatic colorectal tumors, and murine metastatic melanoma. DsiRNA delivery was homogeneous in tumor sections, selective over normal liver and independent of apolipoprotein-E binding. Significant tumor growth inhibition was achieved in Wnt-dependent colorectal and hepatocellular carcinoma models, but not in Wnt-independent tumors. Finally, no evidence of accelerated blood clearance or sustained liver transaminase elevation was observed after repeated dosing in nonhuman primates. These data support further investigation to gain mechanistic insight, optimize dose regimens, and identify efficacious combinations with standard-of-care therapeutics. Mol Cancer Ther; 15(9); 2143-54. (c)2016 AACR. PMID- 27390344 TI - Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. AB - Kidney cancer (or renal cell carcinoma, RCC) is the sixth most common malignancy in the United States and one of the relatively few whose incidence is increasing. Because of the near universal resistance which occurs with the use of current treatment regimens, reprogrammed metabolic pathways are being investigated as potential targets for novel therapies of this disease. Borrowing from studies on other malignancies, we have identified the PAK4 and NAD biosynthetic pathways as being essential for RCC growth. We now show, using the dual PAK4/NAMPT inhibitor KPT-9274, that interference with these signaling pathways results in reduction of G2-M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. Mechanistic studies demonstrate that inhibition of the PAK4 pathway by KPT-9274 attenuates nuclear beta-catenin as well as the Wnt/beta-catenin targets cyclin D1 and c-Myc. Furthermore, NAPRT1 downregulation, which we show occurs in all RCC cell lines tested, makes this tumor highly dependent on NAMPT for its NAD requirements, such that inhibition of NAMPT by KPT-9274 leads to decreased survival of these rapidly proliferating cells. When KPT-9274 was administered in vivo to a 786-O (VHL-mut) human RCC xenograft model, there was dose-dependent inhibition of tumor growth with no apparent toxicity; KPT-9274 demonstrated the expected on-target effects in this mouse model. KPT-9274 is being evaluated in a phase I human clinical trial in solid tumors and lymphomas, which will allow this data to be rapidly translated into the clinic for the treatment of RCC. Mol Cancer Ther; 15(9); 2119-29. (c)2016 AACR. PMID- 27390345 TI - Cortical Button Fixation: A Better Patellar Tendon Repair? AB - BACKGROUND: Patellar tendon ruptures require surgical repair to optimize outcomes, but no consensus exists regarding the ideal repair technique. Cortical button fixation is a secure method for tendon repair that has not been studied in patellar tendons. HYPOTHESIS: Cortical button repair is biomechanically superior to the standard transpatellar repair and biomechanically equivalent to suture anchor repair. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-three fresh-frozen cadaveric knees were used to compare 3 techniques of patellar tendon repair after a simulated rupture at the inferior pole of the patella. Repairs were performed at 45 degrees of flexion using a standard transpatellar suture repair (n = 7), polyetheretherketone (PEEK) suture anchor repair (n = 8), or cortical button repair (n = 8). All specimens were tested on a custom apparatus to simulate cyclic open kinetic chain quadriceps contraction from extension to 90o of flexion. Outcomes of gap formation up to 250 cycles, maximum load to failure, and mode of failure were evaluated. RESULTS: Cortical button repair had significantly less gap formation than anchor repair after 1 cycle (P < .001) and 20 cycles (P < .01) and significantly less gap formation than suture repair from 1 to 250 cycles (P < .05). Cortical button repair sustained significantly higher loads to failure than anchor repair and suture repair (P < .001). All suture repairs failed through the suture. Anchor repairs failed at the suture-anchor eyelet interface (n = 4) or by anchor pullout (n = 3). Cortical button repairs either failed through the suture (n = 5), secondary failure of the patellar tendon (n = 2), or subsidence of the button through the anterior cortex of the patella (n = 1). CONCLUSION: Patellar tendon repair using cortical button fixation demonstrated mechanical advantages over suture repair and anchor repair in cadaveric specimens. Cortical button fixation showed less cyclic gap formation and withstood at least twice the load to failure of the construct. CLINICAL RELEVANCE: The biomechanical superiority of cortical button fixation may impart clinical advantages in accelerating postoperative rehabilitation. PMID- 27390346 TI - Exploring the High Reinjury Rate in Younger Patients Undergoing Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Younger age is being increasingly recognized as a risk factor for anterior cruciate ligament (ACL) graft rupture and contralateral ACL injury after ACL reconstruction. Recent reports estimate second ACL injury rates to be in the range of 20% to 40%, which is a significant concern and requires further exploration. PURPOSE: The primary purpose was to determine the rates of graft rupture and injury to the contralateral native ACL in younger athletes. We also sought to explore the influence of sex and age groupings (<18 years vs 18-19 years at the time of surgery) on the risk of subsequent ACL injury. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study cohort consisted of 354 consecutive patients who were younger than 20 years when they underwent their first primary hamstring tendon autograft ACL reconstruction. The number of subsequent ACL injuries (graft rupture or a contralateral injury to the native ACL) was determined at a mean follow-up of 5 years (range, 3-10 years). Subgroup analysis included sex and age (<18 years vs 18-19 years at the time of surgery) comparisons. Descriptive statistics were calculated for the timing of ACL graft rupture and contralateral ACL injury. RESULTS: The overall follow-up rate was 89% (316/354). Graft ruptures occurred in 57 patients (18%) at an average time of 1.8 years after surgery. Almost half (47%) occurred within the first postoperative year, and 74% occurred within the first 2 years. The highest graft rupture rate of 28.3% was in the youngest males (<18 years), and this was significantly higher than in females of the same age (12.9%), as well as in male patients older than 18 years (13.8%). Contralateral ACL injuries occurred in 56 patients (17.7%) at an average time of 3.7 years after surgery. There were no significant age- or sex based differences for contralateral ACL injuries. The total number of patients who had at least 1 further ACL injury subsequent to the primary surgery was 110 (35%). CONCLUSION: The high rate of subsequent ACL injury in younger patients was confirmed. Early graft ruptures were more prevalent in patients who underwent surgery when they were younger than 18 years versus those in the 18- to 19-year age group. Males had higher rates of graft rupture than did females, with the youngest males (<18 years) at the highest risk in the investigated cohort. PMID- 27390347 TI - Preclinical Assessment of CD171-Directed CAR T-cell Adoptive Therapy for Childhood Neuroblastoma: CE7 Epitope Target Safety and Product Manufacturing Feasibility. AB - PURPOSE: The identification and vetting of cell surface tumor-restricted epitopes for chimeric antigen receptor (CAR)-redirected T-cell immunotherapy is the subject of intensive investigation. We have focused on CD171 (L1-CAM), an abundant cell surface molecule on neuroblastomas and, specifically, on the glycosylation-dependent tumor-specific epitope recognized by the CE7 monoclonal antibody. EXPERIMENTAL DESIGN: CD171 expression was assessed by IHC using CE7 mAb in tumor microarrays of primary, metastatic, and recurrent neuroblastoma, as well as human and rhesus macaque tissue arrays. The safety of targeting the CE7 epitope of CD171 with CE7-CAR T cells was evaluated in a preclinical rhesus macaque trial on the basis of CD171 homology and CE7 cross reactivity. The feasibility of generating bioactive CAR T cells from heavily pretreated pediatric patients with recurrent/refractory disease was assessed. RESULTS: CD171 is uniformly and abundantly expressed by neuroblastoma tumor specimens obtained at diagnoses and relapse independent of patient clinical risk group. CD171 expression in normal tissues is similar in humans and rhesus macaques. Infusion of up to 1 * 108/kg CE7-CAR+ CTLs in rhesus macaques revealed no signs of specific on-target off-tumor toxicity. Manufacturing of lentivirally transduced CD4+ and CD8+ CE7-CAR T-cell products under GMP was successful in 4 out of 5 consecutively enrolled neuroblastoma patients in a phase I study. All four CE7 CAR T-cell products demonstrated in vitro and in vivo antitumor activity. CONCLUSIONS: Our preclinical assessment of the CE7 epitope on CD171 supports its utility and safety as a CAR T-cell target for neuroblastoma immunotherapy. Clin Cancer Res; 23(2); 466-77. (c)2016 AACR. PMID- 27390348 TI - Mutational Landscape and Sensitivity to Immune Checkpoint Blockers. AB - Immunotherapy is currently transforming cancer treatment. Notably, immune checkpoint blockers (ICB) have shown unprecedented therapeutic successes in numerous tumor types, including cancers that were traditionally considered as nonimmunogenic. However, a significant proportion of patients do not respond to these therapies. Thus, early selection of the most sensitive patients is key, and the development of predictive companion biomarkers constitutes one of the biggest challenges of ICB development. Recent publications have suggested that the tumor genomic landscape, mutational load, and tumor-specific neoantigens are potential determinants of the response to ICB and can influence patients' outcomes upon immunotherapy. Furthermore, defects in the DNA repair machinery have consistently been associated with improved survival and durable clinical benefit from ICB. Thus, closely reflecting the DNA damage repair capacity of tumor cells and their intrinsic genomic instability, the mutational load and its associated tumor specific neoantigens appear as key predictive paths to anticipate potential clinical benefits of ICB. In the era of next-generation sequencing, while more and more patients are getting the full molecular portrait of their tumor, it is crucial to optimally exploit sequencing data for the benefit of patients. Therefore, sequencing technologies, analytic tools, and relevant criteria for mutational load and neoantigens prediction should be homogenized and combined in more integrative pipelines to fully optimize the measurement of such parameters, so that these biomarkers can ultimately reach the analytic validity and reproducibility required for a clinical implementation. Clin Cancer Res; 22(17); 4309-21. (c)2016 AACR. PMID- 27390349 TI - Quadruple-Negative GIST Is a Sentinel for Unrecognized Neurofibromatosis Type 1 Syndrome. AB - PURPOSE: The majority of gastrointestinal stromal tumors (GIST) are driven by KIT, PDGFRA, or, less commonly, BRAF mutations, and SDH gene inactivation is involved in a limited fraction of gastric lesions. However, about 10% of GISTs are devoid of any of such alterations and are poorly responsive to standard treatments. This study aims to shed light on the molecular drivers of quadruple negative GISTs. EXPERIMENTAL DESIGN: Twenty-two sporadic quadruple-negative GISTs with no prior association with Neurofibromatosis Type 1 syndrome were molecularly profiled for a panel of genes belonging to tyrosine kinase pathways or previously implicated in GISTs. For comparison purposes, 24 GISTs carrying KIT, PDGFRA, or SDH gene mutations were also analyzed. Molecular findings were correlated to clinicopathologic features. RESULTS: Most quadruple-negative GISTs featured intestinal localization, with a female predilection. About 60% (13/22) of quadruple-negative tumors carried NF1 pathogenic mutations, often associated with biallelic inactivation. The analysis of normal tissues, available in 11 cases, indicated the constitutional nature of the NF1 mutation in 7 of 11 cases, unveiling an unrecognized Neurofibromatosis Type 1 syndromic condition. Multifocality and a multinodular pattern of growth were common findings in NF1 mutated quadruple-negative GISTs. CONCLUSIONS: NF1 gene mutations are frequent in quadruple-negative GISTs and are often constitutional, indicating that a significant fraction of patients with apparently sporadic quadruple-negative GISTs are affected by unrecognized Neurofibromatosis Type 1 syndrome. Hence, a diagnosis of quadruple-negative GIST, especially if multifocal or with a multinodular growth pattern and a nongastric location, should alert the clinician to a possible Neurofibromatosis Type 1 syndromic condition. Clin Cancer Res; 23(1); 273-82. (c)2016 AACR. PMID- 27390351 TI - Understanding deep roots and their functions in ecosystems: an advocacy for more unconventional research. AB - BACKGROUND: Deep roots are a common trait among a wide range of plant species and biomes, and are pivotal to the very existence of ecosystem services such as pedogenesis, groundwater and streamflow regulation, soil carbon sequestration and moisture content in the lower troposphere. Notwithstanding the growing realization of the functional significance of deep roots across disciplines such as soil science, agronomy, hydrology, ecophysiology or climatology, research efforts allocated to the study of deep roots remain incommensurate with those devoted to shallow roots. This is due in part to the fact that, despite technological advances, observing and measuring deep roots remains challenging. SCOPE: Here, other reasons that explain why there are still so many fundamental unresolved questions related to deep roots are discussed. These include the fact that a number of hypotheses and models that are widely considered as verified and sufficiently robust are only partly supported by data. Evidence has accumulated that deep rooting could be a more widespread and important trait among plants than usually considered based on the share of biomass that it represents. Examples that indicate that plant roots have different structures and play different roles with respect to major biochemical cycles depending on their position within the soil profile are also examined and discussed. CONCLUSIONS: Current knowledge gaps are identified and new lines of research for improving our understanding of the processes that drive deep root growth and functioning are proposed. This ultimately leads to a reflection on an alternative paradigm that could be used in the future as a unifying framework to describe and analyse deep rooting. Despite the many hurdles that pave the way to a practical understanding of deep rooting functions, it is anticipated that, in the relatively near future, increased knowledge about the deep rooting traits of a variety of plants and crops will have direct and tangible influence on how we manage natural and cultivated ecosystems. PMID- 27390352 TI - Diversity hotspots of the laurel forest on Tenerife, Canary Islands: a phylogeographic study of Laurus and Ixanthus. AB - BACKGROUND AND AIMS: Macaronesian laurel forest is among the worldwide hotspots of threatened biodiversity. With increasing evidence that woodland composition on the Canary Islands changed dramatically during the last few thousand years, the aim of this study was to find evidence for substantial recent population dynamics of two representative species from laurel forest. METHODS: Amplified fragment length polymorphism (AFLP) was used to evaluate fine-scaled genetic variation of the paradigmatic tree Laurus novocanariensis (Lauraceae) and a long-lived herbaceous gentian from core laurel forest, Ixanthus viscosus (Gentianaceae), on Tenerife. Bioclimatic variables were analysed to study the respective climate niches. A chloroplast DNA screening was performed to evaluate additional genetic variation. KEY RESULTS: Genetic diversity of the laurel tree showed severe geographic partitioning. On Tenerife, fine-scaled Bayesian clustering of genetic variation revealed a western and an eastern gene pool, separated by a zone of high admixture and with a third major gene pool. Compared with genetic clusters found on the other Canary Islands, the East-West differentiation on Tenerife seems to be more recent than differentiation between islands. This is substantiated by the finding of extremly low levels of chloroplast DNA-based polymorphisms. Ixanthus showed no geographic structuring of genetic variation. CONCLUSIONS: Genetic data from Tenerife indicate contemporary gene flow and dispersal on a micro/local scale rather than reflecting an old and relic woodland history. In particular for Laurus, it is shown that this species occupies a broad bioclimatic niche. This is not correlated with its respective distribution of genetic variation, therefore indicating its large potential for contemporary rapid and effective colonization. Ixanthus is more specialized to humid conditions and is mostly found in the natural Monteverde humedo vegetation types, but even for this species indications for long-term persistence in the respective bioclimatically differentiated regions was not find. PMID- 27390350 TI - Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy. AB - PURPOSE: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. EXPERIMENTAL DESIGN: Western blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death. Cellular and mitochondrial reactive oxygen species (ROS) production was measured using CellROX and MitoSOX. Inhibitors/shRNA-targeting ROS, JNK and RIP1 kinase (RIPK1) were used to investigate the mechanism of cell killing. The synergistic interaction between oHSV and bortezomib was calculated using a Chou-Talalay analysis. NK cells isolated from normal human blood were co-cultured with tumor cells to evaluate cellular interactions. Q-PCR, ELISA, and FACS analysis were used to evaluate NK cell activation. Intracranial tumor xenografts were used to evaluate antitumor efficacy. RESULTS: Combination treatment with bortezomib- and oHSV-induced necroptotic cell death and increased the production of mitochondrial ROS and JNK phosphorylation. Inhibitors/shRNA of RIPK1 and JNK rescued synergistic cell killing. Combination treatment also significantly enhanced NK cell activation and adjuvant NK cell therapy of mice treated with bortezomib and oHSV improved antitumor efficacy. CONCLUSIONS: This study provides a significant rationale for triple combination therapy with bortezomib, oHSV, and NK cells to improve efficacy, in glioblastoma patients. Clin Cancer Res; 22(21); 5265-76. (c)2016 AACRSee related commentary by Suryadevara et al., p. 5164. PMID- 27390354 TI - Seed dormancy and germination changes of snowbed species under climate warming: the role of pre- and post-dispersal temperatures. AB - BACKGROUND AND AIMS: Climate warming has major impacts on seed germination of several alpine species, hence on their regeneration capacity. Most studies have investigated the effects of warming after seed dispersal, and little is known about the effects a warmer parental environment may have on germination and dormancy of the seed progeny. Nevertheless, temperatures during seed development and maturation could alter the state of dormancy, affecting the timing of emergence and seedling survival. Here, the interplay between pre- and post dispersal temperatures driving seed dormancy release and germination requirements of alpine plants were investigated. METHODS: Three plant species inhabiting alpine snowbeds were exposed to an artificial warming treatment (i.e. +1.5 K) and to natural conditions in the field. Seeds produced were exposed to six different periods of cold stratification (0, 2, 4, 8, 12 and 20 weeks at 0 degrees C), followed by four incubation temperatures (5, 10, 15 and 20 degrees C) for germination testing. KEY RESULTS: A warmer parental environment produced either no or a significant increase in germination, depending on the duration of cold stratification, incubation temperatures and their interaction. In contrast, the speed of germination was less sensitive to changes in the parental environment. Moreover, the effects of warming appeared to be linked to the level of (physiological) seed dormancy, with deeper dormant species showing major changes in response to incubation temperatures and less dormant species in response to cold stratification periods. CONCLUSIONS: Plants developed under warmer climates will produce seeds with changed germination responses to temperature and/or cold stratification, but the extent of these changes across species could be driven by seed dormancy traits. Transgenerational plastic adjustments of seed germination and dormancy shown here may result from increased seed viability, reduced primary and secondary dormancy state, or both, and may play a crucial role in future plant adaptation to climate change. PMID- 27390353 TI - Root exudate of Solanum tuberosum is enriched in galactose-containing molecules and impacts the growth of Pectobacterium atrosepticum. AB - BACKGROUND AND AIMS: Potato (Solanum tuberosum) is an important food crop and is grown worldwide. It is, however, significantly sensitive to a number of soil borne pathogens that affect roots and tubers, causing considerable economic losses. So far, most research on potato has been dedicated to tubers and hence little attention has been paid to root structure and function. METHODS: In the present study we characterized root border cells using histochemical staining, immunofluorescence labelling of cell wall polysaccharides epitopes and observation using laser confocal microscopy. The monosaccharide composition of the secreted exudates was determined by gas chromatography of trimethylsilyl methylglycoside derivatives. The effects of root exudates and secreted arabinogalactan proteins on bacterial growth were investigated using in vitro bioassays. KEY RESULTS: Root exudate from S. tuberosum was highly enriched in galactose-containing molecules including arabinogalactan proteins as major components. Treatment of the root with an elicitor derived from Pectobacterium atrosepticum, a soil-borne pathogen of potato, altered the composition of the exudates and arabinogalactan proteins. We found that the growth of the bacterium in vitro was differentially affected by exudates from elicited and non-elicited roots (i.e. inhibition versus stimulation). CONCLUSIONS: Taken together, these findings indicate that galactose-containing polymers of potato root exudates play a central role in root-microbe interactions. PMID- 27390355 TI - Physicochemical Characterization of Aerosol Generated in the Gas Tungsten Arc Welding of Stainless Steel. AB - OBJECTIVES: Exposure to stainless steel (SS) welding aerosol that contain toxic heavy metals, chromium (Cr), manganese (Mn), and nickel (Ni), has been associated with numerous adverse health effects. The gas tungsten arc welding (GTAW) is commonly applied to SS and produces high number concentration of substantially smaller particles compared with the other welding techniques, although the mass emission rate is low. Here, a field study in a workshop with the GTAW as principal welding technique was conducted to determine the physicochemical properties of the airborne particles and to improve the understanding of the hazard the SS welding aerosols pose to welders. METHODS: Particle number concentration and number size distribution were measured near the breathing zone (50cm from the arc) and in the middle of the workshop with condensation particle counters and electrical mobility particle sizers, respectively. Particle morphology and chemical composition were studied using scanning and transmission electron microscopy and energy-dispersive X-ray spectroscopy. RESULTS: In the middle of the workshop, the number size distribution was unimodal with the geometric mean diameter (GMD) of 46nm. Near the breathing zone the number size distribution was multimodal, and the GMDs of the modes were in the range of 10 30nm. Two different agglomerate types existed near the breathing zone. The first type consisted of iron oxide primary particles with size up to 40nm and variable amounts of Cr, Mn, and Ni replacing iron in the structure. The second type consisted of very small primary particles and contained increased proportion of Ni compared to the proportion of (Cr + Mn) than the first agglomerate type. CONCLUSIONS: The alterations in the distribution of Ni between different welding aerosol particles have not been reported previously. PMID- 27390356 TI - Co-operative leukemogenesis in acute myeloid leukemia and acute promyelocytic leukemia reveals C/EBPalpha as a common target of TRIB1 and PML/RARA. AB - The PML/RARA fusion protein occurs as a result of the t(15;17) translocation in the acute promyelocytic leukemia subtype of human acute myeloid leukemia. Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia, including acute promyelocytic leukemia. We previously demonstrated that gain of chromosome 8-containing MYC is of central importance in trisomy 8, but the role of the nearby TRIB1 gene has not been experimentally addressed in this context. We have now tested the hypothesis that both MYC and TRIB1 have functional roles underlying leukemogenesis of trisomy 8 by using retroviral vectors to express MYC and TRIB1 in wild-type bone marrow and in marrow that expressed a PML/RARA transgene. Interestingly, although MYC and TRIB1 readily co-operated in leukemogenesis for wild-type bone marrow, TRIB1 provided no selective advantage to cells expressing PML/RARA. We hypothesized that this lack of co-operation between PML/RARA and TRIB1 reflected a common pathway for their effect: both proteins targeting the myeloid transcription factor C/EBPalpha. In support of this idea, TRIB1 expression abrogated the all-trans retinoic acid response of acute promyelocytic leukemia cells in vitro and in vivo Our data delineate the common and redundant inhibitory effects of TRIB1 and PML/RARA on C/EBPalpha providing a potential explanation for the lack of selection of TRIB1 in human acute promyelocytic leukemia, and highlighting the key role of C/EBPs in acute promyelocytic leukemia pathogenesis and therapeutic response. In addition, the co operativity we observed between MYC and TRIB1 in the absence of PML/RARA show that, outside of acute promyelocytic leukemia, gain of both genes may drive selection for trisomy 8. PMID- 27390357 TI - Baseline bone involvement in multiple myeloma - a prospective comparison of conventional X-ray, low-dose computed tomography, and 18flourodeoxyglucose positron emission tomography in previously untreated patients. PMID- 27390359 TI - A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients. AB - The role of pharmacokinetic-guided dosing of factor concentrates in hemophilia is currently a subject of debate and focuses on long-term prophylactic treatment. Few data are available on its impact in the perioperative period. In this study, a population pharmacokinetic model for currently registered factor VIII concentrates was developed for severe and moderate adult and pediatric hemophilia A patients (FVIII levels <0.05 IUmL-1) undergoing elective, minor or major surgery. Retrospective data were collected on FVIII treatment, including timing and dosing, time point of FVIII sampling and all FVIII plasma concentrations achieved (trough, peak and steady state), brand of concentrate, as well as patients' and surgical characteristics. Population pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Population pharmacokinetic parameters were estimated in 75 adults undergoing 140 surgeries (median age: 48 years; median weight: 80 kg) and 44 children undergoing 58 surgeries (median age: 4.3 years; median weight: 18.5 kg). Pharmacokinetic profiles were best described by a two-compartment model. Typical values for clearance, intercompartment clearance, central and peripheral volume were 0.15 L/h/68 kg, 0.16 L/h/68 kg, 2.81 L/68 kg and 1.90 L/68 kg. Interpatient variability in clearance and central volume was 37% and 27%. Clearance decreased with increasing age (P<0.01) and increased in cases with blood group O (26%; P<0.01). In addition, a minor decrease in clearance was observed when a major surgical procedure was performed (7%; P<0.01). The developed population model describes the perioperative pharmacokinetics of various FVIII concentrates, allowing individualization of perioperative FVIII therapy for severe and moderate hemophilia A patients by Bayesian adaptive dosing. PMID- 27390358 TI - Alterations of microRNA and microRNA-regulated messenger RNA expression in germinal center B-cell lymphomas determined by integrative sequencing analysis. AB - MicroRNA are well-established players in post-transcriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNA/target messenger RNA interaction is mostly lacking. Within the International Cancer Genome Consortium Project "Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing", we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNA separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we found expression of three hitherto unreported microRNA. Additionally, we detected recurrent mutations of hsa-miR-142 in diffuse large B cell lymphomas and follicular lymphomas, and editing of the hsa-miR-376 cluster, providing evidence for microRNA editing in lymphomagenesis. To interrogate the direct physical interactions of microRNA with messenger RNA, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNA directly targeted 208 messsenger RNA in the Burkitt lymphomas and 328 messenger RNA in the non-Burkitt lymphoma models. This integrative analysis discovered several regulatory pathways of relevance in lymphomagenesis including Ras, PI3K-Akt and MAPK signaling pathways, also recurrently deregulated in lymphomas by mutations. Our dataset reveals that messenger RNA deregulation through microRNA is a highly relevant mechanism in lymphomagenesis. PMID- 27390360 TI - Definition of bulky disease in early stage Hodgkin lymphoma in computed tomography era: prognostic significance of measurements in the coronal and transverse planes. AB - Disease bulk is an important prognostic factor in early stage Hodgkin lymphoma, but its definition is unclear in the computed tomography era. This retrospective analysis investigated the prognostic significance of bulky disease measured in transverse and coronal planes on computed tomography imaging. Early stage Hodgkin lymphoma patients (n=185) treated with chemotherapy with or without radiotherapy from 2000-2010 were included. The longest diameter of the largest lymph node mass was measured in transverse and coronal axes on pre-treatment imaging. The optimal cut off for disease bulk was maximal diameter greater than 7 cm measured in either the transverse or coronal plane. Thirty patients with maximal transverse diameter of 7 cm or under were found to have bulk in coronal axis. The 4-year overall survival was 96.5% (CI: 93.3%, 100%) and 4-year relapse-free survival was 86.8% (CI: 81.9%, 92.1%) for all patients. Relapse-free survival at four years for bulky patients was 80.5% (CI: 73%, 88.9%) compared to 94.4% (CI: 89.1%, 100%) for non-bulky; Cox HR 4.21 (CI: 1.43, 12.38) (P=0.004). In bulky patients, relapse-free survival was not impacted in patients treated with chemoradiotherapy; however, it was significantly lower in patients treated with chemotherapy alone. In an independent validation cohort of 38 patients treated with chemotherapy alone, patients with bulky disease had an inferior relapse-free survival [at 4 years, 71.1% (CI: 52.1%, 97%) vs 94.1% (CI: 83.6%, 100%), Cox HR 5.27 (CI: 0.62, 45.16); P=0.09]. Presence of bulky disease on multidimensional computed tomography imaging is a significant prognostic factor in early stage Hodgkin lymphoma. Coronal reformations may be included for routine Hodgkin lymphoma staging evaluation. In future, our definition of disease bulk may be useful in identifying patients who are most appropriate for chemotherapy alone. PMID- 27390362 TI - Let's stop fooling ourselves. In RA, only ACR/EULAR criteria define remission and equate with absence of disease! PMID- 27390361 TI - Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner. AB - The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti tumor state both in vitro and in vivo These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia. PMID- 27390363 TI - 'Lower anti-drug antibodies with etanercept biosimilar: can Ctrough explain the differences?'. PMID- 27390364 TI - Child maltreatment hospitalisations in Hong Kong: incidence rate and seasonal pattern. AB - OBJECTIVE: We investigated the incidence and seasonal patterns of child maltreatment hospitalisations in Hong Kong. DESIGN: A retrospective study of subjects aged under 19 years with a primary diagnosis of child maltreatment admitted to hospitals in Hong Kong from 2001 to 2010. Data were retrieved from the centralised database of all 42 public hospitals in the Hospital Authority. MAIN OUTCOME MEASURES: Child maltreatment incidence rate. RESULTS: A consistent seasonal pattern was found for non-sexual maltreatment in children aged 6-18 years (p<0.001). Hospitalisations peaked in May and October but dipped in August and January. No significant seasonal patterns were found for sexual maltreatment or among children under 6 years. The seasonal pattern of child maltreatment coincided with the two school examination periods. The annual child maltreatment hospitalisation rate in Hong Kong in 2010 was 73.4 per 100 000 children under 19 years, more than double that in 2001. CONCLUSIONS: A peculiar seasonal pattern and an alarming increasing trend in child maltreatment hospitalisation were observed in Hong Kong, which we speculated to be related to school examination stress and increasing socioeconomic disparity. Our findings highlighted differences in the trends of child maltreatment between Hong Kong and the West. Professionals and policymakers should be made aware of these trends and develop effective strategies to tackle child maltreatment. PMID- 27390365 TI - Infant home respiratory monitoring using pulse oximetry. AB - Respiratory rate (RR) is a valuable early marker of illness in vulnerable infants, but current monitoring methods are unsuitable for sustained home use. We have demonstrated accurate measurement of RR from brief recordings of pulse oximeter plethysmogram (pleth) trace in full-term neonates in hospital. This study assessed the feasibility of this method in preterm infants during overnight recordings in the home. We collected simultaneous overnight SpO2, pleth and respiratory inductive plethysmography (RIP) on 24 preterm infants in the home. RR from pleth analysis was compared with RR from RIP bands; pleth quality was assessed by the presence of visible artefact. Median (range) RR from RIP and pleth were not significantly different at 42 (25-65) and 42 (25-64) breaths/min. Median (range) % of epochs rejected due to artefact was 20 (8-75) for pleth and 10 (3-53) for RIP. Our results suggest that home RR monitoring by pulse oximeter pleth signal is accurate and feasible. PMID- 27390366 TI - Pregnancy and native heart valve disease. PMID- 27390367 TI - Improved walking speed is associated with lower hospitalisation rates in patients in an exercise-based secondary prevention programme. AB - OBJECTIVE: To determine the relationship between walking speed (WS) maintained during a 1 km test and its improvement on hospitalisation in cardiac outpatients who were referred to an exercise-based secondary prevention programme. METHODS: Hospitalisation was assessed in 1791 patients 3 years after enrolment and related to the WS achieved during a 1 km walk at moderate intensity on a treadmill. Hospitalisation was also assessed during the fourth-to-sixth years as function of improvement in WS in 1111 participants who were re-evaluated 3 years after baseline. RESULTS: Three-year hospitalisation rate across tertiles of baseline WS was 50% for the slow walkers (2.7+/-0.6 km/hour), 41% for the moderate (4.1+/-0.3 km/hour) and 25% for the fast walkers (5.2+/-0.5 km/hour) (p for trend <0.0001), with adjusted HRs (95% CI) of 0.93 (0.74 to 1.17, p=0.53) for intermediate and 0.58 (0.43 to 0.78, p=0.0003) for fast. Every 1 km/hour increase in WS was associated with a 21% reduction in hospitalisation (p<0.0001). Hospitalisation from the fourth-to-sixth years was lower across tertiles of improved WS, with 44% for the low (0.2+/-0.4 km/hour), 34% for the intermediate (0.8+/-0.2 km/hour) and 30% for the high tertile (1.6+/-0.4 km/hour) (p for trend <0.0001). Adjusted HRs were 0.68 (p=0.002) for the intermediate and 0.58 (p<0.0001) for the high tertile. Every 1 km/hour increase in WS was associated with a 35% reduction in hospitalisation (p<0.0001). CONCLUSION: Improvement in WS is associated with a significant, dose-dependent lower rate of all-cause hospitalisation in cardiac outpatients. WS is a simple, easily applied and clinically useful tool for cardiac patients undergoing secondary prevention. PMID- 27390368 TI - Diffuse Alveolar Hemorrhage as a Manifestation of Childhood-Onset Systemic Lupus Erythematosus. AB - BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a devastating clinical syndrome characterized by a falling hematocrit, respiratory insufficiency, and radiographic evidence of pulmonary infiltrates. Literature regarding management of DAH in childhood-onset SLE (cSLE) is limited. METHODS: We reviewed the presentation, management, and outcome of DAH in a pediatric tertiary medical center with one of the largest cSLE cohorts in North America. During a 10 year period 7 of 410 children with cSLE had DAH. RESULTS: The majority of cSLE patients with DAH were male (71%) and Hispanic (57%). The median age at the time of DAH diagnosis was 14 years (range 3 -15 years). DAH was the presenting manifestation of cSLE in 29% of children; 71% presented with DAH within 3 months of their diagnosis. All patients had cough, 86% had dyspnea, and 29% had hemoptysis. All patients had anemia and 71% had thrombocytopenia. Eighty-six percent had hematuria/proteinuria, and a positive anti-double stranded DNA antibody. Chest imaging showed diffuse ground glass opacities in all events. All patients developed respiratory insufficiency (29% supplemental oxygenation and 71% mechanical ventilation). Transfusions were required in 57% of cases. All patients received corticosteroids and additional immunomodulation to achieve disease control. Eighty-six percent of our DAH/cSLE cohort survived their initial event (median follow-up 2.5 years). No survivor required supplemental oxygen or had a DAH recurrence. CONCLUSIONS: SLE should be in the hospitalist's differential diagnosis for any child with respiratory insufficiency, cytopenias, and/or urinary abnormalities. Once cSLE is identified, initiation of aggressive immune suppression with multiple agents may enhance outcomes. PMID- 27390369 TI - Pharmacokinetics, pharmacodynamics, safety and tolerability of an intravaginal ring releasing anastrozole and levonorgestrel in healthy premenopausal women: a Phase 1 randomized controlled trial. AB - STUDY QUESTION: What are suitable doses of the aromatase inhibitor anastrozole (ATZ) and the progestin levonorgestrel (LNG), when delivered to the systemic circulation by an intravaginal ring (IVR), for further clinical development as a potential new therapy for the treatment of endometriosis? SUMMARY ANSWER: Anticipated targets for pharmacokinetics, pharmacodynamics and safety/tolerability were achieved for both drug components of the IVR at the doses investigated, supporting selection of the doses to be investigated in Phase 2 studies. WHAT IS KNOWN ALREADY: Aromatase is a key enzyme in the biosynthesis of estrogens and is known to increase local levels of estradiol (E2) at extragonadal sites. Up-regulation of aromatase expression has been demonstrated in endometriotic lesions and the use of oral aromatase inhibitors has been shown to reduce endometriosis-associated pelvic pain in small-scale clinical trials. STUDY DESIGN, SIZE, DURATION: This Phase 1, randomized, multicentre, parallel group, three-arm, open-label study assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of various IVRs intended for systemic drug delivery. After screening, healthy, ovulating women aged 18-35 years were randomized to use IVRs releasing one of the three ATZ/LNG dose combinations (in vitro nominal daily drug release rates on Day 29: ATZ/LNG 500 ug/20 ug [low dose], ATZ/LNG 1000 ug/30 ug [mid dose] or ATZ/LNG 1500 ug/40 ug [high dose]) for two consecutive 28-day wearing periods without a treatment break. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty women were included in the per protocol set. The primary variables were plasma concentrations of ATZ and LNG at the end of each treatment period and the mean size of largest follicle-like structures (FLSs) over 56 days. Serum concentrations of several hormones were also evaluated, with emphasis on E2 levels. MAIN RESULTS AND THE ROLE OF CHANCE: At the end of the first treatment period, geometric mean plasma concentrations of LNG and ATZ, respectively, were 0.228 and 12.5 ug/l for the low dose, 0.269 and 19.8 ug/l for the mid dose and 0.384 and 37.3 ug/l for the high dose; results were similar at the end of the second treatment period. Over the entire treatment period, mean FLS sizes were higher in all three treatment groups than during the pretreatment cycle; more women in the mid- and high-dose groups had FLSs of at least 30 mm (32-45%) than those in the low-dose group (14-24%). Changes in the mean size of FLSs were similar to those reported for low-dose progestin-only oral contraceptives and generally resolved during the 2-month treatment period. Serum E2 levels were decreased, but only one woman in each of the mid- and high-dose groups, and no woman in the low-dose group, had a serum E2 level below 20 pg/ml in both cycles. All ATZ and LNG combinations showed good tolerability. LIMITATIONS, REASONS FOR CAUTION: This was an exploratory study; no formal power calculation was performed. WIDER IMPLICATIONS OF THE FINDINGS: The results of this first-in-human study of the ATZ/LNG IVR facilitated the selection of ATZ and LNG doses to be investigated in the Phase 2 studies of patients with endometriosis. STUDY FUNDING/COMPETING INTEREST: The study was funded by Bayer Pharma AG. T.R. is an employee of DINOX GmbH, which received funding from Bayer Pharma AG to perform this study. M.-H.S.-M., K.W., R.N., S.K., J.K., H.S. and B.R. are or have been employees of Bayer Pharma AG. H.S. is a named inventor on EP 2 552 404 B1, a patent application relating to this work. TRIAL REGISTRATION NUMBER: EudraCT number: 2011-005620-18. TRIAL REGISTRATION DATE: 16 November 2011. DATE OF FIRST PATIENT'S ENROLMENT: 14 March 2012. PMID- 27390371 TI - Research in Family Medicine by Family Physicians for the Practice of Family Medicine. AB - This issue lays out challenges for family medicine researchers. Each article increases our understanding of solutions to common problems in family medicine, yet with each, one can readily see the next challenge based on the newly gained knowledge. One of the goals of the JABFM is to encourage research in family medicine for family medicine. Here we combine our usual editors' notes with thoughts about what the next research studies could, and hopefully will, be. PMID- 27390370 TI - Does the surgeon's experience have an impact on outcome after total arterial revascularization with composite T-grafts? A risk factor analysis. AB - OBJECTIVES: When composite T-grafting is performed, total arterial revascularization (TAR) can be accomplished with only two grafts. There is the belief that composite grafting poses a risk of graft failure due to its single inflow via the left internal thoracic artery (LITA). High surgical quality is essential for left internal thoracic artery preparation, T-grafting and length estimation. We investigated whether the surgeon's experience influences postoperative outcome. METHODS: We analysed the data of 1080 consecutive patients (88% male, age: 62 +/- 9 years) who underwent composite T-grafting between 1996 and 2011 in our institution. Patients were operated on either by experienced surgeons (Group A) or by surgeons early on in their career (Group B). Primary end points were mortality, myocardial ischaemia, graft dysfunction and low cardiac output syndrome. Secondary end-points were persistent neurologic deficits (PNDs), blood transfusions and re-thoracotomy. Logistic regression analysis was performed to reveal independent risk factors for adverse outcome. RESULTS: Patients in Group B had a lower logistic EuroSCORE (2.8 vs 2.3%; P < 0.05), longer operative times (cross-clamp time: 41 +/- 11 vs 47 +/- 14 min; P < 0.001) and received less anastomoses (3.2 +/- 0.7 vs 3.1 +/- 0.7, P = 0.005). Mortality was low in both groups (Group A 0.6% vs Group B 0.4%; P = 1.0). Myocardial ischaemia occurred in 2.3% (Group A) and 2.5% (Group B; P = 0.82). Graft dysfunction was seen in 0.6% (Group A) and 1.4% (Group B; P = 0.25). Incidence of postoperative low cardiac output syndrome was comparable (Group A 1.4% vs Group B 0.7%; P = 0.53). Both groups showed similar incidence of secondary end-points (persistent neurologic deficit: Group A 2.9 vs 3.2% in Group B; P = 0.84; re-thoracotomy: 1.6% in Group A vs 1.8% in Group B, P = 1.0). Blood transfusions were more common in Group B (P = 0.005). Less surgical experience could only be identified as an independent risk factor for blood transfusion (P = 0.001). CONCLUSIONS: Total arterial revascularization with composite T-grafts can be performed safely by surgeons with different surgical experience. Despite differences in surgical performance parameters (e.g. operation times, blood transfusions), complication rates were extremely low, irrespective of the surgeon's operative experience. Surgeons can be introduced to these procedures in an early phase of training. PMID- 27390372 TI - Telehealth: A Very Useful Tool That Enables and Improves Patient Access. PMID- 27390373 TI - Who is Using Telehealth in Primary Care? Safety Net Clinics and Health Maintenance Organizations (HMOs). AB - Despite rapid advancements in telehealth services, only 15% of family physicians in a 2014 survey reported using telehealth; use varied widely according to the physician's practice setting or designation. Users were significantly more likely than nonusers to work in federally designated "safety net" clinics and health maintenance organizations (HMOs) but not more likely than nonusers to report working in a patient-centered medical home (PCMH) or accountable care organization. PMID- 27390374 TI - The Fit Family Challenge: A Primary Care Childhood Obesity Pilot Intervention. AB - BACKGROUND: Childhood obesity has increased dramatically over several decades, and the American Academy of Pediatrics has recommended primary care practices as ideal sites for the identification, education, and implementation of therapeutic interventions. The objective of this study was to describe the implementation and results for the Fit Family Challenge (FFC), a primary care-based childhood obesity intervention. METHODS: A single-intervention pilot project that trains primary care practices on childhood obesity guidelines and implementation of a family-focused behavior modification curriculum. A total of 29 family medicine and pediatric community practices in Colorado participated. Participants included 290 patients, aged 6 to 12 years, with a body mass index (BMI) above the 85th percentile. The main outcome measure included the feasibility of implementation of a childhood obesity program in primary care; secondary outcomes were changes in BMI percentile, BMI z-scores, blood pressure, and changes in lifestyle factors related to childhood obesity. RESULTS: Implementation of FFC is feasible, statically significant changes were seen for decreases in BMI percentile and BMI z-scores for participants who completed 9 to 15 months of follow-up; lifestyle factors related to childhood obesity in proved Spanish-speaking families and food insecurity were associated with less follow-up time (P < .01). CONCLUSIONS: A primary care-based childhood obesity intervention may result in significant clinical and lifestyle changes. PMID- 27390375 TI - Family Medicine Panel Size with Care Teams: Impact on Quality. AB - PURPOSE: The demand for comprehensive primary health care continues to expand. The development of team-based practice allows for improved capacity within a collective, collaborative environment. Our hypothesis was to determine the relationship between panel size and access, quality, patient satisfaction, and cost in a large family medicine group practice using a team-based care model. METHODS: Data were retrospectively collected from 36 family physicians and included total panel size of patients, percentage of time spent on patient care, cost of care, access metrics, diabetic quality metrics, patient satisfaction surveys, and patient care complexity scores. We used linear regression analysis to assess the relationship between adjusted physician panel size, panel complexity, and outcomes. RESULTS: The third available appointments (P < .01) and diabetic quality (P = .03) were negatively affected by increased panel size. Patient satisfaction, cost, and percentage fill rate were not affected by panel size. A physician-adjusted panel size larger than the current mean (2959 patients) was associated with a greater likelihood of poor-quality rankings (<=25th percentile) compared with those with a less than average panel size (odds ratio [OR], 7.61; 95% confidence interval [CI], 1.13-51.46). Increased panel size was associated with a longer time to the third available appointment (OR, 10.9; 95% CI, 1.36-87.26) compared with physicians with panel sizes smaller than the mean. CONCLUSIONS: We demonstrated a negative impact of larger panel size on diabetic quality results and available appointment access. Evaluation of a family medicine practice parameters while controlling for panel size and patient complexity may help determine the optimal panel size for a practice. PMID- 27390376 TI - Patient Portal Use and Blood Pressure Control in Newly Diagnosed Hypertension. AB - BACKGROUND: Current evidence that patient portal use improves disease management is inconclusive. Randomized controlled trials have found no benefit of Web-based patient-provider communication for blood pressure (BP) control, but patients from these studies were not selected for uncontrolled hypertension, nor did measures of portal use occur in a real-world setting, as captured in the electronic medical record. This study determined whether patient portal use by patients with treated, incident hypertension was associated with achieving BP control. METHODS: Between 2008 to 2010, 1571 patients with an incident hypertension diagnosis, ages 21 to >89 years, were identified from an academic medical center primary care patient data registry. Cox proportional hazard models were computed to estimate the association between portal use and incident BP control during follow-up (2011 2015), before and after adjusting for covariates. Covariates included sociodemographics, smoking, obesity and other physical and mental health comorbidities, and volume of health care utilization. RESULTS: After adjusting for age, portal users were more likely than nonusers to achieve BP control (hazard ratio, 1.24; 95% confidence interval, 1.06-1.45). After adjustment for sociodemographics, portal use was no longer associated with BP control (hazard ratio, 0.98; 95% confidence interval, 0.83-1.16). CONCLUSIONS: Patient sociodemographic factors, including race, sex, and socioeconomic status, account for the observation that portal use leads to BP control among persons with newly diagnosed hypertension. Further research is warranted to determine whether there are benefits of portal use for other chronic conditions. PMID- 27390377 TI - C-Reactive Protein Level as Diagnostic Marker in Young Febrile Children Presenting in a General Practice Out-of-Hours Service. AB - BACKGROUND: It is unclear how well a C-reactive protein (CRP) value predicts a serious infection (SI) in young febrile children in general practice. METHODS: This prospective cohort study with 1-week follow-up included children, aged 3 months to 6 years, presenting with fever to a general practitioner out-of-hours service. We evaluate whether CRP level has predictive value for diagnosing a child at risk for an SI either at presentation or during follow-up. The index test was CRP <=20 mg/L (rule out an SI) and >80 mg/L (rule in an SI). The reference standard was referral to a pediatric emergency department or diagnosis of an SI. The main outcome measure was CRP value. RESULTS: CRP level was available for 440 children. To rule out an SI, CRP <=20 mg/L did not change the probability of having no SI (87.5%). CRP >80 mg/L increased the probability of having an SI from 11.4% (pretest probability) to 21.2% (posttest probability). In children without a diagnosis of SI at presentation, CRP could not predict an SI during follow-up (CRP >80 mg/L: positive likelihood ratio, 2.1, 95% confidence interval, 1.3-3.5; CRP <=20 mg/L: negative likelihood ratio, 0.9, 95% confidence interval, 0.7-1.2). CONCLUSIONS: In general practice CRP has little clinically relevant value in discriminating febrile children in need of medical care from those who are not. PMID- 27390378 TI - Communicating Findings of Delayed Diagnostic Evaluation to Primary Care Providers. AB - BACKGROUND: We previously found that an intervention involving electronic algorithms to detect delays in follow-up of cancer-related abnormal or "red-flag" findings and communicating this information to primary care providers (PCPs) led to more timely diagnostic evaluation. In this study, we examined the effectiveness of various communication strategies to inform PCPs about the delayed follow-up. METHODS: After identifying follow-up delays through electronic health record-based algorithms and record reviews, we communicated this information to PCPs using 3 escalating steps. First, we sent secure E-mails. If no evidence of follow-up was found in a medical record review after 1 week, we made up to 3 attempts to reach the PCPs or their nurses via telephone. If they could not be reached, we informed clinic directors as the third and final step. In this analysis, we evaluate PCPs' follow-up in response to these methods of communication. RESULTS: A total of 733 patients with follow-up delays were identified (369 patients in the intervention group and 364 patients in the control group). Communicating information to PCPs about possible follow-up delays led to decreased times to diagnostic evaluation, but communication related to delays did not always lead to follow-up for the patients in the intervention group. Specifically, secure E-mails led to follow-up in 11.1% of cases (41 of 369), telephone calls led to follow-up in 68.6% of cases (225 of 328), and contacting clinic directors led to follow-up in 5 of 11 cases in which communication escalated to this level. CONCLUSION: Strategies to communicate to PCPs information on delayed follow-up of findings suspicious for cancer were useful, but not fail-safe. Additional back-up strategies, such as using case coordinators, might be needed. PMID- 27390379 TI - Provision of Recommended Chronic Pain Assessment and Management in Primary Care: Does Patient-Centered Medical Home (PCMH) Recognition Make a Difference? AB - BACKGROUND: Chronic pain (CP) care in the patient-centered medical home (PCMH) model has not been well studied. We assessed whether PCMH recognition is associated with increased provision of key practice recommendations for CP assessment and management. METHODS: Chart reviews were completed for 12 primary care practices affiliated with one health system in the Cincinnati Area Research and Improvement Group (CARInG). Recommendations were abstracted and compared based on PCMH status: 3 practices had received prior PCMH level 3 recognition, 5 were in an ongoing process of applying, and 4 had no recognition and were not applying. RESULTS: A total of 485 charts were reviewed from 65 PCPs. Eight of 10 key recommendations were documented more often in the prior and ongoing PCMH cohorts, including assessing pain severity, function, psychosocial distress, and substance abuse, and using structured instruments for these assessments. There were fewer differences between the cohorts in the management of chronic opioids, with only the ongoing PCMH cohort having higher documentation for 5 of the 7 recommendations, including performing urine drug screens and using a structured instrument to assess for misuse. CONCLUSIONS: These findings support the usefulness of the PCMH model in managing patients with CP, but patient outcomes need to be addressed in future studies. PMID- 27390380 TI - System Transformation in Patient-Centered Medical Home (PCMH): Variable Impact on Chronically Ill Patients' Utilization. AB - BACKGROUND: Research connecting patient-centered medical homes (PCMHs) with improved quality and reduced utilization is inconsistent, possibly because individual domains of change, and the stage of change, are not incorporated in the research design. The objective of this study was to examine the association between stage and domain of change and patterns of health care utilization. METHODS: This was a cross-sectional observational study that including 87 Minnesota clinics certified as medical homes. Patients included those receiving management for diabetes or cardiovascular disease with insurance coverage by payers participating in the study. PCMH transformation stage was defined by practice systems in place, with measurements summarized in 5 domains. Health care utilization was measured by total utilization, frequency of outpatient visits and prescriptions, and occurrence of inpatient and emergency department visits. RESULTS: PCMH transformation was associated with few changes in utilization, but there were important differences by the underlying domains of change. We demonstrate meaningful differences in the impact of PCMH transformation by diagnosis cohort and comorbidity status of the patient. CONCLUSIONS: Because the association of health care utilization with PCMH transformation varied by transformation domain and patient diagnosis, practice leaders need to be supported by research incorporating detailed measures of PCMH transformation. PMID- 27390381 TI - A Primary Care Panel Size of 2500 Is neither Accurate nor Reasonable. AB - Primary care panel sizes are an important component of primary care practices. Determining the appropriate panel size has implications for patient access, physician workload, and care comprehensiveness and will have an impact on quality of care. An often quoted standard panel size is 2500. However, this number seems to arise in the literature anecdotally, without a basis in research. Subsequently, multiple studies observed that a panel size of 2500 is not feasible because of time constraints and results in incomplete preventive care and health care screening services. In this article we review the origins of a panel size of 2500, review the subsequent work examining this number and effectively debunking it as a feasible panel size, and discuss the importance of primary care physicians setting an appropriate panel size. PMID- 27390382 TI - Antibiotic Prophylaxis for Patients with a History of Total Joint Replacement. AB - As the population ages and people remain active into the 7th and 8th decades of life, the frequency of total joint replacement is increasing. Following joint replacement surgery, patients inevitably require various invasive procedures as part of their routine health maintenance, including, but not limited to, dental care, colonoscopy, cystoscopy, and cardiac catheterization. There is scant evidence to support the use of periprocedural prophylactic antibiotics in the prevention of late total joint infection. The guidelines for the usage of periprocedural antibiotics have changed as knowledge of the pathophysiology of joint infection has evolved. We review the current recommendations from subspecialty academic organizations regarding antibiotic prophylaxis for patients undergoing routine urologic, gastrointestinal, dental, and cardiac procedures after total joint replacement. PMID- 27390383 TI - The Performance of Fertility Awareness-based Method Apps Marketed to Avoid Pregnancy. AB - INTRODUCTION: In recent years there has been an explosion in the development of medical apps, with more than 40,000 apps now available. Nearly 100 apps allow women to track their fertility and menstrual cycles and can be used to avoid or achieve pregnancy. Apps offer a convenient way to track fertility biomarkers. However, only some use evidence-based fertility awareness-based methods (FABMs), which with ideal use have rates of effectiveness similar to those of commonly used forms of hormonal birth control. Since having a baby or preventing a pregnancy are important responsibilities, it is critical that women and couples have access to reliable, evidence-based apps that allow them to accurately track their fertility. METHODS: We developed a tool to evaluate and rate fertility apps. This tool is specifically designed to help couples avoid pregnancy. RESULTS: Results showed that the majority of fertility apps are not based on evidence-based FABMs or include a disclaimer discouraging use for avoiding pregnancy. However, at least 1 app in each FABM category (except symptohormonal methods) had a perfect score on accuracy. CONCLUSION: Relying solely on an app to use an FABM, without appropriate training in the method, may not be sufficient to prevent pregnancy. PMID- 27390384 TI - Evaluating the Evidence for Choosing WiselyTM in Primary Care Using the Strength of Recommendation Taxonomy (SORT). AB - OBJECTIVE: The goal of this study was to evaluate the quality of evidence supporting primary care-relevant Choosing Wisely(TM) recommendations using the Strength of Recommendation Taxonomy (SORT). METHODS: All Choosing Wisely "top 5" lists published by American medical specialty societies through June 2014 were reviewed for relevance to primary care. Both authors independently applied SORT to generate an evidence letter grade for each of the included recommendations, relying on citations supplied by the nominating organizations. RESULTS: Of 310 recommendations, 224 were identified as being relevant to primary care. We rated 43 (19%) as SORT level of evidence A, 57 (25%) as B, and 124 (55%) as C. CONCLUSION: We found that a majority of primary care-relevant Choosing Wisely recommendations are based on expert consensus or disease-oriented evidence. Further research is warranted to strengthen the evidence base supporting these recommendations in order to improve their acceptance and implementation into primary care. PMID- 27390385 TI - Re: Over Half of Graduating Family Medicine Residents Report More Than $150,000 in Educational Debt. PMID- 27390386 TI - Response: Re: Over Half of Graduating Family Medicine Residents Report More Than $150,000 in Educational Debt. PMID- 27390388 TI - A classification of the use of research indicators. AB - Research performance indicators are broadly used, for a range of purposes. The scientific literature on research indicators has a strong methodological focus. There is no comprehensive overview or classification of the use of such indicators. In this paper we give such a classification of research indicator use. Using the journal Scientometrics as a starting point we scrutinized recent journal literature on scientometrics, bibliometrics, research policy, research evaluation, and higher education in order to spot paragraphs or sections that mention indicator use. This led to a classification of research indicator use with 21 categories which can be grouped into five main categories. PMID- 27390387 TI - Protocol for a retrospective, controlled cohort study of the impact of a change in Nature journals' editorial policy for life sciences research on the completeness of reporting study design and execution. AB - In recent years there has been increasing concern about the rigor of laboratory research. Here we present the protocol for a study comparing the completeness of reporting of in vivo and in vitro research carried in Nature Publication Group journals before and after the introduction of a change in editorial policy (the introduction of a set of guidelines for reporting); and in similar research published in other journals in the same periods. PMID- 27390389 TI - BigDebug: Debugging Primitives for Interactive Big Data Processing in Spark. AB - Developers use cloud computing platforms to process a large quantity of data in parallel when developing big data analytics. Debugging the massive parallel computations that run in today's data-centers is time consuming and error-prone. To address this challenge, we design a set of interactive, real-time debugging primitives for big data processing in Apache Spark, the next generation data intensive scalable cloud computing platform. This requires re-thinking the notion of step-through debugging in a traditional debugger such as gdb, because pausing the entire computation across distributed worker nodes causes significant delay and naively inspecting millions of records using a watchpoint is too time consuming for an end user. First, BIGDEBUG's simulated breakpoints and on-demand watchpoints allow users to selectively examine distributed, intermediate data on the cloud with little overhead. Second, a user can also pinpoint a crash-inducing record and selectively resume relevant sub-computations after a quick fix. Third, a user can determine the root causes of errors (or delays) at the level of individual records through a fine-grained data provenance capability. Our evaluation shows that BIGDEBUG scales to terabytes and its record-level tracing incurs less than 25% overhead on average. It determines crash culprits orders of magnitude more accurately and provides up to 100% time saving compared to the baseline replay debugger. The results show that BIGDEBUG supports debugging at interactive speeds with minimal performance impact. PMID- 27390390 TI - Perceptions of Healthy Eating in Four Alberta Communities: A Photovoice Project. AB - Peoples' perceptions of healthy eating are influenced by the cultural context in which they occur. Despite this general acceptance by health practitioners and social scientists, studies suggest that there remains a relative homogeneity around peoples' perceptions that informs a hegemonic discourse around healthy eating. People often describe healthy eating in terms of learned information from sources that reflect societies' norms and values, such as the Canada Food Guide and the ubiquitous phrase "fruits and vegetables". Past research has examined how built environments shape people's access to healthy living options, such as distribution of grocers versus convenience stores and fast food restaurants. Often overlooked is an in-depth understanding of how social contexts interact with built environments, molding peoples' perceptions of healthy eating. This paper reports on perceptions of healthy eating in four communities across Alberta, Canada. A photovoice methodology was employed to elicit perceptions of healthy eating with 35 participants. This study illustrates how participants' photographs and their stories convey multiple meanings about healthy eating within their own lives and communities. Findings suggest that a 'local' context is an important part of the discourse centered around the promotion of healthy eating practices in these and potential other communities. PMID- 27390391 TI - Effect of duration of smartphone use on muscle fatigue and pain caused by forward head posture in adults. AB - [Purpose] The effect of duration of smartphone use on neck and shoulder muscle fatigue and pain was investigated in adults with forward head posture. [Subjects and Methods] Thirty-four adults with forward head posture were classified into groups by duration of smartphone use: 11 used a smartphone for 10 minutes each (group 1), 12 for 20 minutes each (group 2), and 11 for 30 minutes each (group 3). Fatigue cervical erector spinae and upper trapezius muscles was measured by electromyography, and pain before and after the experiment was evaluated using Visual Analog Scale (VAS) scores. [Results] There was a significant difference in the degree of fatigue in the left upper trapezius muscles in group 2 and left cervical erector spinae and bilateral upper trapeziuses group 3. There was a significant difference in fatigue in the left upper trapezius in groups 1 and 3. The VAS showed significant differences in all groups before and after the experiment and between groups 1 and 3. [Conclusion] Pain and fatigue worsened with longer smartphone use. This study provided data on the proper duration of smartphone use. Correct posture and breaks of at least 20 minutes are recommend when using smartphones. PMID- 27390392 TI - Immediate effects of the trunk stabilizing exercise on static balance parameters in double-leg and one-leg stances. AB - [Purpose] The purpose of this study was to evaluate the immediate effect of stabilizing exercise using the PNF technique on standing balance in one-leg and double-leg stances. [Subjects and Methods] The present study recruited 34 healthy participants from a local university. The Participants performed four balance tests (double-leg stance with and without vision, one-leg stance with and without vision), before and after exercise. The exercise consisted of exercises performed using PNF techniques (stabilizing reversal and rhythmic stabilization), which were applied to facilitate trunk musculature. To examine balance ability, total displacement of the center of pressure was measured during balance tests. [Results] The total anterior-posterior center of pressure displacement was significantly reduced after applying rhythmic stabilization compared before exercise regardless of the balance test conditions. [Conclusion] The present results suggest that trunk stability exercise using rhythmic stabilization could effectively enhance balance ability under one-leg and double-leg conditions. PMID- 27390393 TI - Relationship of lower extremity alignment during the wall squat and single-leg jump: assessment of single-leg landing using three-dimensional motion analysis. AB - [Purpose] The purpose of this study was to evaluate the relationship between malalignment and lower-extremity injury and to determine the optimal dynamic alignment of the lower extremity with wall squats. [Subjects and Methods] Healthy individuals from one therapy school were enrolled and assigned to a wall squat normal or abnormal group based on their forms during wall squats. The abnormal group was found to be more prone to lower-extremity injury on three-dimensional motion analysis. Eight students from each group were randomly chosen for the study. The effects of single-leg landing movements were assessed using three dimensional motion analysis. [Results] In the sagittal plane, significant flexion of the hip and knee joints occurred 0.02 and 0.04 seconds after initial foot contact with the ground in the normal and abnormal groups, respectively. In the frontal plane, significant adduction of the hip joint occurred at 0.07 seconds in the abnormal group. [Conclusion] The abnormal group tended to display later flexion of the hip and knee joints and narrower hip, knee, and ankle range of motion than the normal group, suggesting that dynamic alignment of the lower extremity in the abnormal group likely made them susceptible to injury. PMID- 27390394 TI - Effects of breathing exercises on lung capacity and muscle activities of elderly smokers. AB - [Purpose] Elderly smokers have a reduced chest diameter due to weakening of the respiratory muscles, and this results in decreased ventilation, leading to a vicious circle. Therefore, the present study investigated the effects of an intervention program to enhance the pulmonary function and muscle activity of elderly smokers. [Subjects and Methods] Participants were randomly assigned to one of two experimental groups or a control (CG) group. The experimental groups performed exercises three times per week for six weeks, whereas the CG performed no exercises. One of the experimental groups performed a Feedback Breathing Exercise (FBE) for 15 minutes, and the other repeated three sets of Balloon Blowing Exercises (BBE) with sufficient rest of more than one minute between sets. [Results] In the experimental groups, FVC, FEV1/FVC, PEF and muscle activity of the rectus abdominis significantly improved after four weeks, but no significant differences were observed in FEV1 or VC after six weeks. [Conclusion] The results show that FBE and BBE improved the pulmonary functions of elderly smokers, demonstrating the potential benefits of the development of various training methods using balloons, and group programs, including recreational factors, for increasing respiratory muscles strength. PMID- 27390395 TI - The contributions of balance to gait capacity and motor function in chronic stroke. AB - [Purpose] The aim of this study was to identify the contributions of balance to gait and motor function in chronic stroke. [Subjects and Methods] Twenty-three outpatients participated in a cross-sectional assessment. Gait ability was assessed using the functional ambulation category, self-paced 10-m walking speed, and fastest 10-m walking speed. Standing balance and trunk control measures included the Berg Balance Scale and the Trunk Impairment Scale. Univariate and multivariate regression analyses were performed. [Results] Balance was the best predictor of the FAC, self-paced walking speed, and fastest walking speed, accounting for 57% to 61% of the variances. Additionally, the total score of TIS was the only predictor of the motor function of the lower limbs and the dynamic balance of TIS was a predictor of the motor function of the upper limbs, accounting for 41% and 29% of the variance, respectively. [Conclusion] This study demonstrated the relative contribution of standing balance and trunk balance to gait ability and motor function. They show that balance has a high power of explanation of gait ability and that trunk balance is a determinant of motor function rather than gait ability. PMID- 27390396 TI - Effect of mat pilates exercise on postural alignment and body composition of middle-aged women. AB - [Purpose] This study attempted to examine whether Pilates is an effective exercise for improving the postural alignment and health of middle-aged women. [Subjects and Methods] The participants in this study were 36 middle-aged women (20 in the experimental group, 16 in the control group). The experimental group participated in Pilates exercise sessions three times a week for 12 weeks. Body alignment and composition measurements before and after applying the Pilates exercise program were performed with a body composition analyzer and a three dimensional scanner. [Results] Postural alignment in the sagittal and horizontal planes was enhanced in the Pilates exercise group. Trunk alignment showed correlations with body fat and muscle mass. [Conclusion] The Pilates exercises are performed symmetrically and strengthen the deep muscles. Moreover, the results showed that muscle mass was correlated with trunk postural alignment and that the proper amount of muscle is critical in maintaining trunk postural alignment. PMID- 27390397 TI - The effect of postural control and balance on femoral anteversion in children with spastic cerebral palsy. AB - [Purpose] The aim of the study was to investigate the relationships between femoral anteversion and functional balance and postural control in children with spastic cerebral palsy. [Subjects and Methods] Twenty children with spastic cerebral palsy (mean age=12.4 +/- 4.5) with grosss motor functional classification system levels I, II, and III were recruited for this study. Functional balance was evaluated using the Pediatric Balance Scale, postural control was evaluated using the Trunk Control Measurement Scale, and femoral anteversion was assessed with a handheld goniometer using the great trochanter prominence method. [Results] The results indicated that there was significant correlation between femoral anteversion and Trunk Control Measurement Scale dynamic reaching score. There were no significant correlation between femoral anteversion and the Trunk Control Measurement Scale static sitting balance, Trunk Control Measurement Scale selective movement control, total Trunk Control Measurement Scale and Pediatric Balance Scale results. [Conclusion] Increased femoral anteversion has not correlation with functional balance, static sitting, and selective control of the trunk. Femoral anteversion is related to dynamic reaching activities of the trunk, and this may be the result of excessive internal pelvic rotation. It is important for the health professionals to understand that increased femoral anteversion needs to be corrected because in addition to leading to femoral internal rotation during walking, it also effects dynamic reaching activities of spastic children with cerebral palsy. PMID- 27390399 TI - Effects of lumbar stabilization exercises on the flexion-relaxation phenomenon of the erector spinae. AB - [Purpose] This study evaluated the differences in the flexion-relaxation phenomenon (FRP) of the right and left erector spinae muscles in asymptomatic subjects and the effect of lumbar stabilization exercises on these differences. [Subjects and Methods] Twenty-six participants (12 in the exercise group and 14 in the control group) with a difference in the FRP in the right and left erector spinae muscles were recruited from among healthy students attending Silla University. The exercise group performed two lumbar stabilization exercises (back bridge exercise and hand-knee exercise) for 4 weeks. The control group did not exercise. [Results] No significant group-by-exercise interaction was found. The right and left erector spinae muscles did show a difference in FRP between the control and exercise groups (119.2 +/- 69.2 and 131.1 +/- 85.2 ms, respectively). In addition, the exercise group showed a significant decrease in post-exercise (50.0 +/- 27.0 ms) compared to pre-exercise (112.3 +/- 41.5 ms) differences in the right and left FRP. [Conclusion] These results suggest that lumbar stabilization exercises may counter asymmetry of the FRP in the erector spinae muscles, possibly preventing low back pain in the general population. PMID- 27390398 TI - The sitting and rising test for assessing people with chronic stroke. AB - [Purpose] To investigate the inter-rater and test-retest reliability of the sitting-rising test (SRT), the correlations of sitting-rising test scores with measures of strength, balance, community integration and quality of life, as well as the cut-off score which best discriminates people with chronic stroke from healthy older adults were investigated. [Subjects and Methods] Subjects with chronic stroke (n=30) and healthy older adults (n=30) were recruited. The study had a cross-sectional design, and was carried out in a university rehabilitation laboratory. Sitting-rising test performance was scored on two occasions. Other measurements included ankle dorsiflexor and plantarflexor strength, the Fugl Meyer assessment, the Berg Balance Scale, the timed up and go test, the five times sit-to-stand test, the limits of stability test, and measures of quality of health and community integration. [Results] Sitting-rising test scores demonstrated good to excellent inter-rater and test-retest reliabilities (ICC=0.679 to 0.967). Sitting-rising test scores correlated significantly with ankle strength, but not with other test results. The sitting-rising test showed good sensitivity and specificity. A cut-off score of 7.8 best distinguished healthy older adults from stroke subjects. [Conclusions] The sitting-rising test is a reliable and sensitive test for assessing the quality of sitting and rising movements. Further studies with a larger sample are required to investigate the test's validity. PMID- 27390400 TI - The correlation between occupational performance and well-being in stroke patients. AB - [Purpose] This study was performed to evaluate the occupational performance of stroke patients and their environment by occupational self-assessment and to investigate the relationship between occupational performance and well-being. [Subjects and Methods] This study enrolled ninety-two stroke patients who were receiving occupational therapy at a general hospital, a rehabilitation hospital, or a community welfare center in the cities of Busan and Gimhae, Republic of Korea. Occupational performance and well-being were investigated with Occupational Self-Assessment Version 2.2 and the Personal Well-being Index-Adult. [Results] Analysis of the correlation between occupational performance as assessed by the "Myself" and "My Environment" sections of Occupational Self Assessment Version 2.2 and well-being revealed moderate positive correlation for both sections. [Conclusion] The relationship between occupational performance and well-being was identified. Further studies are needed to reveal whether improvement of occupational performance could affect well-being in various dimensions. PMID- 27390401 TI - Test-retest reliability of the safe driving behavior measure for community dwelling elderly drivers. AB - [Purpose] The Safe Driving Behavior Measure (SDBM) is a self-report measurement tools that assesses the safe-driving behaviors of the elderly. The purpose of this study was to evaluate the test-retest reliability of the SDBM among community-dwelling elderly drivers. [Subjects and Methods] A total of sixty-one community-dwelling elderly were enrolled to investigate the reliability of the SDBM. The SDBM was assessed in two sessions that were conducted three days apart in a quiet and well-organized assessment room. That test-retest reliability of overall scores and three domain scores of the SDBM were statistically evaluated using intraclass correlation coefficients [ICC (2.1)]. Pearson correlation coefficients were used to quantify bivariate associations among the three domains of the SDBM. [Results] The SDBM demonstrated excellent rest-retest reliability for community-dwelling elderly drivers. The Cronbach alpha coefficients of the three domains of person-vehicle (0.979), person-environment (0.944), and person vehicle-environment (0.971) of the SDBM indicate high internal consistency. [Conclusion] The results of this study suggest that the SDBM is a reliable measure for evaluating the safe- driving of automobiles by community-dwelling elderly, and is adequate for detecting changes in scores in clinical settings. PMID- 27390403 TI - Reliability and validity assessment of an apathy scale for home-care patients with Parkinson's disease: a structural equation modeling analysis. AB - [Purpose] Based on the Starkstein Apathy Scale, an apathy scale was developed for home-care patients with Parkinson's disease using structural equation modeling (SEM), with which the data compatibility of extraction factors can be verified. [Subjects and Methods] The participants were 122 home-care patients with Parkinson's disease (mean age: 70.9 +/- 7.8 years) who were member of the Aomori branch or Tohoku/Hokkaido block of the Japan Parkinson's Disease Association. A questionnaire survey (anonymous, self-administered) was carried out by distributing and collecting questionnaires by mail or a collective survey at a workshop. Construct validity was evaluated by confirmatory factor analysis using SEM. Internal consistency was investigated using Cronbach's alpha coefficient. Criterion-related validity was assessed by correlation analysis with the total score of the Beck Depression Inventory. [Results] Concerning construct validity, 11 of the 14 question items of the original scale were extracted. Cronbach's alpha of this scale was 0.939. For criterion-related validity, Spearman's rank correlation coefficient was 0.831. [Conclusion] The construct validity, internal consistency, and criterion-related validity of the 11-item apathy scale were confirmed. The 11-item apathy scale can serve as a useful tool for the efficient and effective assessment of rehabilitation, establishment of rehabilitation goals and programs for patients with Parkinson's disease. PMID- 27390402 TI - Acute effects of neural mobilization and infrared on the mechanics of the median nerve. AB - [Purpose] This study analyzed the acute effects of infrared and neural mobilization on the median nerve on the range of elbow extension of the dominant limb. [Subjects and Methods] Forty participants from university, neurologically asymptomatic, 12 males and 28 females (22.8 +/- 1.9 years), were randomly divided into four groups: Group 1 (control) rested for 25 minutes in the supine position; Group 2 received the specific neural mobilization for the median nerve; Group 3 received an application of infrared for 15 minutes on the forearm; Group 4 received the same application of infrared followed by neural mobilization. The goniometric parameters of elbow extension were evaluated after the intervention. [Results] Significant differences of extension value were observed between Group 1 and Group 3 (15.75 degrees), and between Group 1 and Group 4 (14.60 degrees), and the average higher in Group 3 (26.35 degrees). [Conclusion] This research provides new experimental evidence that NM in relation to superficial heat produces an immediate effect on elbow range of motion versus NM isolated. PMID- 27390404 TI - Lymphoedema functioning, disability and health questionnaire Turkish version: translation, cross-cultural adaptation and validation. AB - [Purpose] The purpose of this study was to adapt the Lymphoedema Functioning, Disability and Health Questionnaire into the Turkish language, and to evaluate the psychometric properties of the Turkish version in patients with breast cancer related lymphedema. [Subjects and Methods] After the translation, inter-rater and test-retest reliability were assessed between patients and physiotherapists using the intra-class correlation coefficient. Thirty patients with breast cancer related lymphedema were asked to fill out the Turkish version of the Lymphoedema Functioning, Disability and Health Questionnaire two times, one week apart. Internal consistency was tested using Cronbach's alpha, and the test-retest reliability was assessed by calculating the intra-class correlation coefficient. Construct validity was investigated by comparing the results of the Lymphoedema Functioning, Disability and Health and Short Form-36 questionnaires. [Results] The test-retest reliability and inter-tester reliability of the Lymphedema Functioning, Disability and Health Questionnaire total score, physical function score, mental function score, household activities score, mobility activities score, life and social activities score were excellent. [Conclusion] The Turkish version of the Lymphoedema Functioning, Disability and Health Questionnaire was found to be valid and reliable for patients with breast cancer related lymphedema. PMID- 27390405 TI - Effects of elastic band exercise on subjects with rounded shoulder posture and forward head posture. AB - [Purpose] This study performed to investigate the effect of elastic band exercise program on the posture of subjects with rounded shoulder and forward head posture. [Subjects and Methods] The body length, forward shoulder angle, craniovertebral angle, and cranial rotation angle of participants (n=12) were measured before and after the exercise program. Furthermore, the thicknesses of the pectoralis major, rhomboid major, and upper trapezius were measured using an ultrasonographic imaging device. The exercises program was conducted with elastic bands, with 15 repetitions per set and 3 sets in total. [Results] The length of the pectoralis major, forward shoulder angle, and craniovertebral angle showed significant changes between before and after the exercise program, whereas the changes in the other measurements were not significant. The thickness of the upper trapezius showed a significant increase between before and after the elastic band exercise. [Conclusion] These findings suggest that the elastic band exercise program used in the study is effective for lengthening the pectoralis major and correcting rounded shoulder and forward head posture. PMID- 27390406 TI - Effect of exhalation exercise on trunk muscle activity and oswestry disability index of patients with chronic low back pain. AB - [Purpose] This study investigated the effect of exhalation exercises on trunk muscle activity and Oswestry Disability Index by inducing trunk muscle activity through increasing intra-abdominal pressure and activating muscles, contributing to spinal stability. [Subjects and Methods] This intervention program included 20 male patients with chronic low back pain. A total of 10 subjects each were randomly assigned to an exhalation exercise group as the experimental group and a spinal stabilization exercise group as the control group. [Results] There were significant differences in the activities of the rectus abdominis, transverse abdominis, external oblique abdominal, and erector spinae muscles as well as in the Oswestry Disability Index within the experimental group. There were meaningful differences in the activities of the rectus abdominis, external oblique abdominal, and erector spinae muscles and in the Oswestry Disability Index within the control group. In addition, there was a meaningful intergroup difference in transverse abdominis muscle activity alone and in the Oswestry Disability Index. [Conclusion] The breathing exercise effectively increased muscle activity by training gross and fine motor muscles in the trunk. Moreover, it was verified as a very important element for strengthening body stability because it both released and prevented low back pain. PMID- 27390407 TI - Recovery levels after eccentric and concentric loading in maximal force. AB - [Purpose] The aim of this study was to compare the differences in recovery periods after maximal concentric and eccentric exercises. [Subjects and Methods] Twenty-two participants voluntarily participated and were divided into two groups: the athlete and sedentary groups. An incremental treadmill running test was performed until exhaustion. During the subsequent passive recovery session, heart rate and venous blood lactate level were determined every 3 minutes until the venous blood lactate level reached 2 mmol/l. The same test protocol was implemented 15 days later. [Results] Both groups showed significantly shorter running durations in concentric exercise, while significant differences were found between the athlete and sedentary groups in terms of venous blood lactate level responses. In addition, there were significant differences between the athlete and sedentary groups in terms of running duration and heart rate in concentric and eccentric exercises. [Conclusion] The present study revealed no difference between the athlete and sedentary groups in terms of recovery durations after eccentric and concentric loadings, although the athletes demonstrated faster recovery in terms of HR compared with the sedentary group. It was thought that concentric exercises cause greater physiological responses. PMID- 27390408 TI - The effects of visual stimuli on EEG mu rhythms in healthy adults. AB - [Purpose] Several action observation/imagery training studies have been conducted in patients with limited physical activity showing improvements in motor function. However, most studies compared effects of action observation and imagery, so little is known about the changes caused by subsequent observation of target objects. Moreover, few studies analyzed brain wave changes in the EEG mu rhythm. [Subjects and Methods] Eighteen healthy female adults participated in this study, and were divided into two groups: 'Visual Stimuli' and 'Non-Visual Stimuli'. EEG amplitude in the 8-13 Hz frequency band over the sensorimotor cortex was evaluated. [Results] Significant mu suppression was obtained in the action observation trials. Mu power showed a main effect of visual stimuli, with decreased power during action observation, and increased power post-observation in both conditions. Comparing the 'Visual Stimuli' and 'Non-Visual Stimuli' conditions during the post-observation period, mu power demonstrated a greater increase in the 'Non-Visual Stimuli' condition. Furthermore, mu power was lower post-observation than pre-observation. [Conclusion] These results show the effects of visual input between maintaining target objects and no visual input, and their relevance to modulations of the mirror neuron system. It also suggests that greater visual input may be more effective for cognitive rehabilitation. PMID- 27390409 TI - Association between mean platelet volume and bone mineral density in postmenopausal women. AB - [Purpose] Osteoporosis is an inflammatory disease, and platelets play a critical role in bone remodeling. Mean platelet volume has been shown to be influenced by inflammation. Our aim was to evaluate the relationship between mean platelet volume and bone mineral density in postmenopausal women. [Subjects and Methods] The records of female patients who had been referred to a tertiary hospital for bone mineral density analysis were retrospectively reviewed. [Results] A total of 175 patients (mean age: 61.3 +/- 9.0 years) were enrolled. Overall, 72% (126/175) of patients met the criteria for osteoporosis. Mean platelet volume was found to be inversely correlated with body mass index. There was a significant positive correlation between mean platelet volume and femoral neck bone mineral density in our normal weight osteoporotic group, whereas there was a significant negative correlation in our overweight-obese osteoporotic group. The negative correlation between mean platelet volume and femoral neck bone mineral density in the overweight-obese osteoporotic group persisted after adjustment for confounding factors. Multivariate analyses revealed that mean platelet volume was significantly associated with femoral neck bone mineral density in osteoporotic patients in both our normal weight and overweight-obese groups. [Conclusion] Regardless of mechanisms, mean platelet volume might be used as a biomarker for osteoporosis in clinical settings. PMID- 27390410 TI - Effects of a dynamic chair on pelvic mobility, fatigue, and work efficiency during work performed while sitting: a comparison of dynamic sitting and static sitting. AB - [Purpose] Working while sitting for long periods can cause lumbar pain, fatigue, and reduced work efficiency. How a dynamic chair with a seat that moves three dimensionally affects pelvic mobility before and after work, work efficiency, and post-work fatigue were examined. [Subjects and Methods] Subjects were 17 healthy adults (10 males, 7 females, mean age 21.8 +/- 2.7 years). Subjects performed a 30-min Kraepelin test under two conditions: sitting in a standard office chair and sitting in a dynamic sitting balance chair. Root mean square (RMS) values of pelvic movement measured by a triaxial accelerometer during 30 minutes of work, finger-floor distance before and after work, lumbar fatigue, and pelvic movement RMS values during finger-floor distance measurement were used as outcome measures. [Results] Pelvic movement RMS values collected every 5 minutes during 30 minutes of work were significantly higher while sitting in the dynamic balance chair. Changes in pelvic movement RMS values during finger-floor distance measurement after work and amount of work performed during 30 minutes were significantly higher and lumbar fatigue was significantly lower for the dynamic balance chair. [Conclusion] Dynamic sitting maintained or increased pelvic flexibility. The dynamic balance chair may effectively help workers work continuously in seated postures with little fatigue. PMID- 27390411 TI - Effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness of female patients with metabolic syndrome. AB - [Purpose] The purpose of this study was to investigate the effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness or female patients with metabolic syndrome. [Subjects and Methods] Subjects were randomly assigned to an exercise group (n=12) or a control group (n=11). Subjects in the exercise group performed aerobic exercise at 60-80% of maximum heart rate for 40 min 5 times a week for 12 weeks. The changes in metabolic syndrome risk factors, resting heart rate, physical fitness, and arterial stiffness were measured and analyzed before and after initiation of the exercise program to determine the effect of exercise. Arterial stiffness was assessed based on brachial-ankle pulse wave velocity (ba-PWV). [Results] Compared to the control group; The metabolic syndrome risk factors (weight, % body fat, waist circumference, systolic blood pressure, diastolic blood pressure, and HDL Cholesterol) were significantly improved in the exercise: resting heart rate was significantly decreased; VO2max, muscle strength and muscle endurance were significantly increased; and ba-PWV was significantly decreased. [Conclusion] Aerobic exercise had beneficial effects on the resting heart rate, physical fitness, and arterial stiffness of patients with metabolic syndrome. PMID- 27390412 TI - Effect of visual stimulus using central and peripheral visual field on postural control of normal subjects. AB - [Purpose] This study investigated the effects of visual stimulus using central and peripheral vision fields on postural control. [Subjects and Methods] The subjects consisted of 40 young adult volunteers (15 males, 25 females) who had been informed of the study purpose and procedure. The subjects were randomly divided into four groups of differing visual stimulus. Each group was given visual intervention in a standing position for 3 minutes. Postural control was evaluated before and after visual intervention. [Results] The results of the functional reach test and body sway test showed significant differences among the four groups. [Conclusion] The two-way peripheral vision-field group showed significantly more body sway after visual intervention than the other three groups. This finding may suggest two-way peripheral vision field is a more effective visual stimulus for training postural control and balance. PMID- 27390413 TI - Health science students' perceptions of motor and sensory aphasia caused by stroke. AB - [Purpose] This study explored health science students' perceptions of motor aphasia and sensory aphasia caused by stroke to provide basic material for the improvement of rehabilitation practitioners' perceptions of aphasia. [Subjects and Methods] The subjects of this study were 642 freshmen and sophomores majoring in health science. Perceptions of aphasia were surveyed on a semantic differential scale using the Anchoring Vignette Method and the difference in perception of the two types of aphasia was analyzed using multi-dimensional scaling. [Results] The analysis revealed that motor aphasia and sensory aphasia have mutually corresponding images. Motor aphasia had high levels of 'quiet', 'passive' 'dumb', 'unstable' and 'gloomy' images, while sensory aphasia had high levels of 'noisy', 'unstable', 'cheerful', 'sensitive', 'fluctuating in emotions', 'active', 'dumb' and 'gloomy' images. [Conclusion] A systematic education is required to be implemented in the future to improve health science students' negative perceptions of the aftereffects of stroke such as aphasia. PMID- 27390414 TI - Double product break point estimates ventilatory threshold in individuals with type 2 diabetes. AB - [Purpose] To verify the identification of the anaerobic threshold through the double product breakpoint (DPBP) method for individuals with type 2 diabetes. [Subjects and Methods] Nine individuals with T2D (7 females; age=63.2 +/- 8.9 y) and 10 non-diabetic (ND) (7 females; age=58.3 +/- 7.8 y) performed an incremental exercise test on a cycle ergometer. Heart rate (HR), blood pressure (BP) and expired gas were measured at the end of each stage. The ventilatory threshold (VT) and DPBP were considered as the exercise intensities above which an over proportional increases in VE and DP were observed in relation to increasing workload. [Results] No differences were observed between the workloads, HR and VO2 corresponding to the AT identified respectively by VT and DPBP. For the T2D, strong correlations between VT and DBPB workloads (r=0.853), HR (r=0.714), and VO2 (r=0.863) were found. These relationships were similar to those found for the control group (r=0.923; r=0.881; and r=0.863, respectively). [Conclusion] These results demonstrate that the DPBP enables for the prediction of AT and correlated well the VT in both the T2D and ND participants. PMID- 27390415 TI - Effects of whole-body vibration after eccentric exercise on muscle soreness and muscle strength recovery. AB - [Purpose] The aim of this study was to investigate whether or not a single whole body vibration treatment after eccentric exercise can reduce muscle soreness and enhance muscle recovery. [Subjects and Methods] Twenty untrained participants were randomly assigned to two groups: a vibration group (n=10) and control group (n=10). Participants performed eccentric quadriceps training of 4 sets of 5 repetitions at 120% 1RM, with 4 min rest between sets. After that, the vibration group received 3 sets of 1 min whole body vibration (12 Hz, 4 mm) with 30 s of passive recovery between sets. Serum creatine kinase, blood urea nitrogen, muscle soreness (visual analog scale) and muscle strength (peak isometric torque) were assessed. [Results] Creatine kinase was lower in the vibration group than in the control group at 24 h (200.2 +/- 8.2 vs. 300.5 +/- 26.1 U/L) and at 48 h (175.2 +/- 12.5 vs. 285.2 +/- 19.7 U/L) post-exercise. Muscle soreness decreased in vibration group compared to control group at 48 h post-exercise (34.1 +/- 11.4 vs. 65.2 +/- 13.2 mm). [Conclusion] Single whole-body vibration treatment after eccentric exercise reduced delayed onset muscle soreness but it did not affect muscle strength recovery. PMID- 27390416 TI - The effect of a hybrid assistive limb((r)) on sit-to-stand and standing patterns of stroke patients. AB - [Purpose] The Hybrid Assistive Limb((r)) (HAL((r))) robot suit is a powered exoskeleton that can assist a user's lower limb movement. The purpose of this study was to assess the effectiveness of HAL((r)) in stroke rehabilitation, focusing on the change of the sit-to-stand (STS) movement pattern and standing posture. [Subjects and Methods] Five stroke patients participated in this study. Single leg HAL((r)) was attached to each subject's paretic lower limb. The subjects performed STS three times both with and without HAL((r)) use. A tri axial accelerometer was used to assess the STS movement pattern. Forward-tilt angle (FTA) and the time required for STS were measured with and without HAL((r)) use. Surface electromyography (EMG) of STS and standing were recorded to assess the vastus medialis muscle activities of the paretic limb. [Results] The average FTA without HAL((r)) use was 35 degrees and it improved to 43 degrees with HAL((r)) use. The time required for STS was longer for all subjects with HAL((r)) use (without HAL((r)) use: 3.42 s, with HAL((r)) use: 5.11 s). The integrated EMGs of HAL((r)) use compared to those without HAL((r)), were 83.6% and 66.3% for STS and standing, respectively. [Conclusion] HAL((r)) may be effective in improving STS and standing patterns of stroke patients. PMID- 27390417 TI - Effect of aerobic exercise and raloxifene combination therapy on senile osteoporosis. AB - [Purpose] This study assessed the effects of combined application of raloxifene and aerobic exercise on senile osteoporosis. [Subjects and Methods] A total of 70 elderly patients with osteoporosis, who treated at our hospital between April 2013 and August 2014, were divided into equal-sized observation and control groups. The control group was administered raloxifene, whereas the observation group received raloxifene treatment plus aerobic exercise. [Results] Outpatient outcomes were considered dependent variables. After treatment, the two groups differed significantly in terms of lumbar spine (L2-L4) and proximal femoral bone mineral density. The urine pyridine/creatinine ratio decreased significantly and serum calcitonin level increased significantly in the observation group. These differences were statistically significant. [Conclusion] Raloxifene combined with aerobic exercise therapy significantly improves bone density and promotes bone formation in patients with senile osteoporosis. PMID- 27390418 TI - Self-selected intensity, ratings of perceived exertion, and affective responses in sedentary male subjects during resistance training. AB - [Purpose] This study examined the exercise intensity and psychophysiological responses to a self-selected resistance training session in sedentary male subjects. [Subjects and Methods] Twelve sedentary male subjects (35.8 +/- 5.8 years; 25.5 +/- 2.6 kg.m(2)) underwent four sessions at 48-h intervals: familiarization; two sessions of one repetition maximum test and a resistance training session in which they were told to self-select a load to complete 3 sets of 10 repetitions of chest press, leg press, seated rows, knee extension, overhead press, biceps curl, and triceps pushdown exercises. During the latter, the percentage of one repetition maximum, affective responses (feeling scale), and rating of perceived exertion (OMNI-RES scale) were measured. [Results] The percentage of one repetition maximum for all exercises was >51% (14-31% variability), the rating of perceived exertion was 5-6 (7-11% variability), and the affective responses was 0-1 point with large variability. [Conclusion] Sedentary male subjects self-selected approximately 55% of one maximum repetition, which was above the intensity suggested to increase strength in sedentary individuals, but below the recommended intensity to improve strength in novice to intermediate exercisers. The rating of perceived exertion was indicative of moderate intensity and slightly positive affective responses. PMID- 27390419 TI - Analysis of walking variability through simultaneous evaluation of the head, lumbar, and lower-extremity acceleration in healthy youth. AB - [Purpose] The purpose of this study was to clarify whether walking speed affects acceleration variability of the head, lumbar, and lower extremity by simultaneously evaluating of acceleration. [Subjects and Methods] Twenty young individuals recruited from among the staff at Kurashiki Heisei Hospital participated in this study. Eight accelerometers were used to measure the head, lumbar and lower extremity accelerations. The participants were instructed to walk at five walking speeds prescribed by a metronome. Acceleration variability was assessed by a cross-correlation analysis normalized using z-transform in order to evaluate stride-to-stride variability. [Results] Vertical acceleration variability was the smallest in all body parts, and walking speed effect had laterality. Antero-posterior acceleration variability was significantly associated with walking speed at sites other than the head. Medio-lateral acceleration variability of the bilateral hip alone was smaller than the antero posterior variability. [Conclusion] The findings of this study suggest that the effect of walking speed changes on the stride-to-stride acceleration variability was individual for each body parts, and differs among directions. PMID- 27390420 TI - Immediate effect of stretching and ultrasound on hamstring flexibility and proprioception. AB - [Purpose] This research explored the positive effects of self-myofascial release on hamstring muscular flexibility and proprioception and investigated the effectiveness of the stretch combined with therapeutic ultrasound. [Subjects and Methods] This study included 30 healthy university students with no history of pain in the Achilles tendon or hamstring within the recent 6 months. Each participant completed two experiments. In the first experiment (MS), they completed self-myofascial stretching using a foam roller for 7 days. In the second experiment (MSU), the same participants performed the self-myofascial stretching after the 15-minute application of ultrasound. This study involved a pre- and post-test on hamstring muscle flexibility and hip joint proprioception. [Results] The use of self-myofascial stretching in the MS experiment had a significant effect on hamstring muscle flexibility and hip joint proprioception. However, the addition of ultrasound in the MSU experiment had no additive effect. [Conclusion] Self-myofascial stretching immediately increased hamstring muscle flexibility and improved hip joint proprioception, but the addition of pre stretch ultra sound provided no further benefit. PMID- 27390421 TI - Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke. AB - [Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study's findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia. PMID- 27390422 TI - Effects of yogic eye exercises on eye fatigue in undergraduate nursing students. AB - [Purpose] This study was performed to investigate the effects of yogic eye exercises on eye fatigue in undergraduate nursing students. [Subjects and Methods] The study used a pretest-posttest design with a non-equivalent control group. Forty undergraduate nursing students were selected by convenience sampling, with 20 assigned to an exercise group and 20 assigned to a control group. The yogic eye exercise intervention was performed for 60 minutes, two days a week for 8 weeks. It consisted of 8 steps: palming, blinking, sideways viewing, front and sideways viewing, rotational viewing, up and down viewing, preliminary nose tip gazing, and near and distant viewing. Eye fatigue was measured using a questionnaire for evaluating ocular fatigue. [Results] The exercise-group measurements revealed a significantly decreased eye-fatigue score compared with that of the control group. [Conclusion] These findings indicate that yogic eye exercises could reduce the eye fatigue score in undergraduate nursing students. PMID- 27390423 TI - The effects of eye movement training on gait function in patients with stroke. AB - [Purpose] The present study examined the effects of eye movement training on gait function in patients with stroke. [Subjects and Methods] Fourteen patients with stroke were randomly assigned to either an experimental group or a control group. The experimental group underwent eye movement training while the control group underwent general gait training five times per week for six weeks. [Results] Patient walking speed, cadence, and step length were measured by ink-footprint. The experimental group exhibited significant changes in walking speed, cadence, and step length following training, while the control group exhibited no differences. [Conclusion] Findings indicate that eye movement training should be considered as part of a functional gait training program for patients with stroke. PMID- 27390424 TI - The effects of Pilates exercise training on static and dynamic balance in chronic stroke patients: a randomized controlled trial. AB - [Purpose] The purpose of this study was to analyze the effects of Pilates exercise on static and dynamic balance in chronic stroke patients. [Subjects and Methods] Nineteen individuals with unilateral chronic hemiparetic stroke (age, 64.7 +/- 6.9 years; height, 161.7 +/- 7.9 cm; weight, 67.0 +/- 11.1 kg) were randomly allocated to either a Pilates exercise group (PG, n=10) or a control group (CG, n=9). The PG attended 24 exercise sessions conducted over an 8-week period (3 sessions/week). Center of pressure (COP) sway and COP velocity were measured one week before and after the exercise program and compared to assess training effects. [Results] Pilates exercise positively affected both static and dynamic balance in patients with chronic stroke. For static balance, COP sway and velocity in the medial-lateral (M-L) and anterior-posterior (A-P) directions were significantly decreased in the PG after training while no significant differences were found in the CG. For dynamic balance, measured during treadmill walking, the PG showed significantly reduced COP sway and velocity in the M-L and A-P directions for both the paretic and non-paretic leg. [Conclusions] The findings provide initial evidence that Pilates exercise can enhance static and dynamic balance in patients with chronic stroke. PMID- 27390425 TI - Effects of stretching the scalene muscles on slow vital capacity. AB - [Purpose] The purpose of this study was to examine whether stretching of the scalene muscles would improve slow vital capacity (SVC). [Subjects and Methods] The subjects of this study were 20 healthy female students to whom the study's methods and purpose were explained and their agreement for participation was obtained. The SVC was measured using spirometry (Pony FX, COSMED Inc., Italy). The intervention used was stretching of the scalene muscles. Stretching was carried out for 15 min, 10 times at per each portion of scalene muscles: the anterior, middle, and posterior parts. [Results] Expiratory vital capacity (EVC) and tidal volume (Vt) noticeably increased after stretching. However, there were no changes in any of the SVC items in the control group. [Conclusion] This study demonstrated that stretching of the scalene muscles can effectively improve SVC. In particular, we confirmed that stretching of the scalene muscles was effective in increasing EVC and Vt, which are items of SVC. PMID- 27390426 TI - Association between daily activities, process skills, and motor skills in community-dwelling patients after left hemiparetic stroke. AB - [Purpose] The purpose of this study was to evaluate the relationships between daily activities, information processing, and motor skills in individuals with hemineglect after having a left hemiparetic stroke. [Subjects and Methods] The instrumental activities of daily living of 35 patients (22 male and 13 female; age: 57.1 +/- 16.9 years) with hemineglect after having a left hemiparetic stroke were assessed by using three clinical measurement tools, including activity card sorting, assessment of motor and process skills, and the modified Barthel Index. [Results] The results of the regression analysis indicated that the patients' processing skills in instrumental activities of daily living after having a left hemiparetic stroke were reduced. Participation in leisure and social activities was also affected as assessed by using the modified Barthel Index. [Conclusion] This study supports the clinical need for rehabilitation intervention after a left hemiparetic stroke to improve patients' processing skills and independence in performing activities of daily living. PMID- 27390427 TI - A study on balance assessment according to the levels of difficulty in postural control. AB - [Purpose] This study aimed to determine appropriate measures for assessing balance ability according to difficulty level during standing tasks. [Subjects and Methods] The subjects were 56 old (>65 years) and 30 young (20-30 years) adults. By using the Berg balance scale, the subjects were divided into three groups: 29 healthy older (Berg score>=52), 27 impaired older (Berg score>=40), and 30 healthy young (Berg score>=55). One inertial measurement unit sensor was attached at the waist, and the subjects performed standing tasks (1 min/task) with six difficulty levels: eyes open and eyes closed on firm ground, one foam, and two foams. Thirty-nine (24 time-domain, 15 frequency-domain) measures were calculated by using acceleration data. The slope of each derived measure was calculated through the least-squares method. [Results] Five (95% ellipse sway area, root mean squares [anterior-posterior and resultant directions], and mean distance [anterior-posterior and resultant directions] in time domain) of the 39 measures showed significant differences among the groups under specific standing conditions. The slopes of derived measures showed significant differences among the groups and significant correlations with the Berg scores. [Conclusion] The slope according to the difficulty level can be used to assess and discriminate standing balance ability. PMID- 27390428 TI - Effects of mechanical horseback riding velocity on spinal alignment in young adults. AB - [Purpose] This study aimed to determine if the velocity of mechanical horseback riding training can improve spinal alignment in young adults. [Subjects and Methods] Thirty-six subjects were enrolled in this study. The subjects were randomly allocated into high-, moderate-, and low-velocity mechanical horseback riding training groups. All participants completed one 20-minute session per day, 3 days per week, for 6 weeks. The evaluation was performed before and 6 weeks after the training intervention. The spinal alignment was measured by a Formetric III device. The measurement items were kyphotic angle, lordotic angle, trunk inclination, pelvic torsion, pelvic rotation, and lateral deviation. The data were analyzed using analysis of covariance to determine the statistical significance. [Results] The kyphotic angle and trunk inclination were significantly different among the groups. The kyphotic angles of the high- and moderate-velocity groups were significantly lower than that of the low-velocity group after the intervention. The trunk inclination of the high-velocity group was significantly lower than that of the low-velocity group after intervention. [Conclusion] Higher-velocity mechanical horseback-riding training is more effective than lower-velocity mechanical horseback-riding training for improving spinal alignment. PMID- 27390429 TI - Effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by parkinson's disease. AB - [Purpose] This study aimed to investigate the effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by Parkinson's disease. [Subjects and Methods] The subjects of this study were 18 patients who received simultaneous application of postural techniques and expiratory muscle strength training and 15 patients who received expiratory muscle strength training only. Postural techniques were conducted in the order of chin tucking, head rotation, head tilting, bending head back, and lying down, while expiratory muscle strength training was conducted at a resistance level of about 70% of the maximal expiratory pressure. Swallowing recovery was assessed by using the Functional Dysphagia Scale based on videofluoroscopic studies. [Results] The mean value obtained in the videofluoroscopic studies for both groups decreased after the treatment. In the postural techniques plus expiratory muscle strength training group, the decrease was significantly greater than that in the expiratory muscle strength training-only group. [Conclusion] The results imply that simultaneous performance of postural techniques and expiratory muscle strength training is more effective than expiratory muscle strength training alone when applied in the swallowing rehabilitation for patients with dysphagia caused by Parkinson's disease. PMID- 27390430 TI - Correlation between physical function, cognitive function, and health-related quality of life in elderly persons. AB - [Purpose] This study aimed to assess the quality of life of elderly people related to physical function, cognitive function, and health, and devised methods to enhance their health-related quality of life. [Subjects and Methods] This study was conducted from November 2014 to January 2015 in 140 people over 65 registered at welfare centers. Those with a functional psychological disorder or difficulty communicating were excluded. Data were collected for physical function, cognitive function, and health-related quality of life (HRQOL) using an assessment tool and questionnaire for healthy elderly people over 65. Physical function was measured using muscle strength muscle endurance, reaction time, and balance. [Results] Correlations were observed between cognitive function and endurance, reaction time, and balance. Physical HRQOL showed correlations with all domains of physical function; mental HRQOL showed correlations with all items of physical function except muscle strength. Among factors that influence HRQOL, all items except educational background were significant variables. Educational background had no influence on HRQOL. [Conclusion] Interventions will correct factors with a negative influence on HRQOL, utilizing regular checks on physical, cognitive, and other functions of elderly people, with early detection and intervention to enhance HRQOL. Cognitive intervention related to physical and other functions will be applied. PMID- 27390431 TI - Abdominal muscle activity according to knee joint angle during sit-to-stand. AB - [Purpose] This study assessed the activity of the abdominal muscles according to the angle of the knee joints during sit-to-stand. [Subjects and Methods] Thirty healthy adult males participated in this study. Subjects initiated sit-to-stand at knee joint angles of 60 degrees , 90 degrees , or 120 degrees . An electromyography system was used to measure the maximum voluntary isometric contraction of the rectus abdominis, external oblique, and internal oblique and transverse abdominis muscles. [Results] Percent contraction differed significantly among the three knee joint angles, most notably for the internal oblique and transverse abdominis muscles. [Conclusion] Wider knee joint angles more effectively activate the abdominal muscles, especially those in the deep abdomen, than do narrower angles. PMID- 27390432 TI - The effect of Graston technique on the pain and range of motion in patients with chronic low back pain. AB - [Purpose] Clinicians have reported the effects of various instrument assisted soft tissue mobilization (IASTM) in patients. The purpose of this study was to investigated the effects of the Graston technique and general exercise on pain and range of motion (ROM) in patients with CLBP. [Subjects and Methods] 30 patients with CLBP participated in the study (Graston technique: 15; CONTROL: 15). Before and after the 4-week intervention program, pain was assessed using a visual analog scale (VAS). Lumbar ROM was measured using a smartphone. The main effects and interaction were analyzed by two-way repeated ANOVA. [Results] A significant time-by-group interaction was observed for the VAS and ROM. A post hoc paired t-test showed that pain decreased significantly post-intervention within the Graston group. The lumbar ROM significantly increased post intervention in both groups. [Conclusion] The Graston technique and general exercise resulted in pain relief and increased ROM. However, the Graston group showed significantly increased VAS and ROM more than control group. These findings suggest that the Graston technique can be useful as a pain decrease and ROM increase for patients with CLBP. PMID- 27390433 TI - Influence of preliminary exercise training on muscle damage indices in rats after one bout of prolonged treadmill exercise. AB - [Purpose] The purpose of this study was to investigate the effects of exercise on muscle damage indices in male Sprague-Dawley rats. Two groups of rats were trained in either moderate- or high-intensity treadmill running for 4 weeks. Subsequently, the concentrations of creatine kinase, lactate dehydrogenase, and high-sensitivity C-reactive protein were examined following a single bout of prolonged (3-h) intensive exercise. [Subjects and Methods] The study included forty 6-week-old male Sprague-Dawley rats weighing 150-180 g each. The aerobic exercise group was divided into high-intensity (28 m/min) and moderate-intensity (15 m/min) subgroups. Both subgroups were trained for 35 min daily for 6 days per week (excluding Sunday) over a 4-week period. Following training, the high- and moderate-intensity exercise groups and a non-exercise group performed one bout of prolonged (3-h) treadmill exercise for 3 hours at a speed of 15 m/min. [Results] Creatine kinase and lactate dehydrogenase levels differed significantly among the groups. [Conclusion] The preliminary exercise groups showed lower muscle damage and inflammatory response levels than the non-exercise group after the bout of prolonged intensive exercise. PMID- 27390434 TI - Evaluation of tympanic temperature and thermal sensation responses during exercise to verify the positive effects of wearing germanium-coated functional clothing. AB - [Purpose] The present study investigated the effects of wearing germanium-coated functional clothing on tympanic temperature, thermal sensation, heat shock protein 70 (Hsp70), and lactate during endurance exercise. [Subjects and Methods] Nine healthy and untrained male subjects were enrolled. Subjects ran for 60 min on a treadmill (75% heart rate reserve) in the following 2 tests: 1) control test (wearing conventional clothing) and 2) experimental test (wearing germanium coated functional clothing). During each test, the tympanic temperature and thermal sensation were measured, and blood samples were collected immediately before exercise and immediately after exercise. Thermal sensation was measured using a DISC score. [Results] The tympanic temperature immediately after exercise was significantly increased compared to the temperature immediately before exercise in the control test, while no significant change was observed in the experimental test. In both tests, the DISC score and Hsp70 and lactate levels immediately after exercise were significantly increased compared to those immediately before exercise. In addition, the DISC score immediately after exercise was significantly higher in the control test than in the experimental test. [Conclusion] Wearing germanium-coated functional clothing during endurance exercise may have the positive effect of alleviating thermal stress that accumulates in the body during exercise. PMID- 27390435 TI - Effect of trapezius muscle strength on three-dimensional scapular kinematics. AB - [Purpose] This study aimed to investigate the effect of trapezius muscle isometric strength on three-dimensional scapular kinematics in asymptomatic shoulders. [Subjects and Methods] Thirty asymptomatic subjects were included to the study. Isometric strengths of the upper, middle, and lower trapezius muscle were measured using a handheld dynamometer. Three-dimensional scapular kinematics was recorded by an electromagnetic tracking device during frontal and sagittal plane elevation. For each muscle, the cut-off value for muscle strength was determined with the upper bound of the 95% confidence interval, and Student's t test was used to compare the scapular kinematics between subjects with relatively weaker or stronger trapezius muscles. [Results] Shoulders with stronger upper trapezius muscles showed greater upward scapular rotation at 30 degrees , 60 degrees , 90 degrees , and 120 degrees of elevation in the frontal plane. Shoulders with stronger middle trapezius had greater scapular upward rotation at 90 degrees of elevation in the frontal plane. Shoulders with stronger lower trapezius showed greater scapular posterior tilt at 90 degrees of elevation in the sagittal plane. [Conclusion] This study's findings showed that isometric strength of the trapezius muscle affects upward scapular rotation and posterior tilt in asymptomatic shoulders. Therefore, trapezius muscle strength should be assessed and potential weakness should be addressed in shoulder rehabilitation programs. PMID- 27390436 TI - Relation of selective voluntary motor control of the lower extremity and extensor strength of the knee joint in children with spastic diplegia. AB - [Purpose] The aim of this study was to investigate differences in selective voluntary motor control of the lower extremities by objective assessment and determine the relationship between selective voluntary motor control and knee extensor strength in children with spastic diplegia. [Subjects and Methods] Forty individuals who had spastic cerebral palsy, with Gross Motor Function Classification System levels ranging from I to III, were assessed using the Selective Control Assessment of the Lower Extremity and by testing the maximum knee extensor strength. The unaffected side was defined as the lower limb with the higher score, and the affected side was defined as the lower limb with the lower score. [Results] The Selective Control Assessment of the Lower Extremity score on the affected side had a lower average than that on the unaffected side. The scores showed a significant inverse correlation with the maximum knee extensor strength. [Conclusion] There was bilateral difference in the selective voluntary motor control of the lower extremities in children with spastic diplegia, and the selective voluntary motor control of the lower extremity was related to maximum knee extensor strength. PMID- 27390437 TI - Effects of individualized versus group task-oriented circuit training on balance ability and gait endurance in chronic stroke inpatients. AB - [Purpose] The purpose of this study was to analyze the effects of task-oriented circuit training on the balance ability and gait endurance of chronic stroke inpatients. [Subjects and Methods] The participants were 30 patients who had stroke >6 months previously, resulting in a disability such as hemiparesis. The participants were randomly divided into the group task-oriented circuit training group and the individual task-oriented circuit-training group. They performed eight types of modified task-oriented training. Balance ability and gait endurance were measured by using the Berg balance scale questionnaire and the 6 min walk test, respectively, before and after the experiment. [Results] Significant differences were observed between before and after the intervention in all variables. There was a significant difference between groups in Berg balance scale scores; however, no significant differences were seen in the timed up and go test and the 6-min walk test. [Conclusion] The results of this study indicated that group exercise can better improve the balance ability of chronic stroke inpatients after stroke than can individualized exercise intervention. PMID- 27390438 TI - Analysis of scapular kinematics during active and passive arm elevation. AB - [Purpose] Early postoperative passive motion exercise after arthroscopic rotator cuff repair remains controversial. To better understand this issue, this study was aimed at evaluating scapular kinematics and muscle activities during passive arm elevation in healthy subjects. [Subjects and Methods] The dominant shoulders of 27 healthy subjects were examined. Electromagnetic sensors attached to the scapula, thorax, and humerus were used to determine three-dimensional scapular kinematics during active arm elevation with or without external loads and passive arm elevation. Simultaneously, the activities of seven shoulder muscles were recorded with surface and intramuscular fine-wire electrodes. [Results] Compared with active arm elevation, passive elevation between 30 degrees and 100 degrees significantly decreased the scapular upward rotation and increased the glenohumeral elevation angle. However, no significant differences in scapular posterior tilt and external rotation were observed between active and passive arm elevation, and scapular plane kinematics were not affected by muscle activity. [Conclusion] Unlike active motion with or without an external load, passive arm elevation significantly decreased the scapular upward rotation and significantly increased the mid-range glenohumeral elevation. These data, which suggest that passive arm elevation should be avoided during the early postoperative period, may expand the understanding of rehabilitation after arthroscopic rotator cuff repair. PMID- 27390440 TI - Effect of physical therapy frequency on gross motor function in children with cerebral palsy. AB - [Purpose] This study attempted to investigate the effect of physical therapy frequency based on neurodevelopmental therapy on gross motor function in children with cerebral palsy. [Subjects and Methods] The study sample included 161 children with cerebral palsy who attended a convalescent or rehabilitation center for disabled individuals or a special school for children with physical disabilities in South Korea. Gross Motor Function Measure data were collected according to physical therapy frequency based on neurodevelopmental therapy for a period of 1 year. [Results] The correlation between physical therapy frequency and Gross Motor Function Measure scores for crawling and kneeling, standing, walking, running and jumping, and rolling, and the Gross Motor Function Measure total score was significant. The differences in gross motor function according to physical therapy frequency were significant for crawling, kneeling, standing, and Gross Motor Function Measure total score. The differences in gross motor function according to frequency of physical therapy were significant for standing in Gross Motor Function Classification System Level V. [Conclusion] Intensive physical therapy was more effective for improving gross motor function in children with cerebral palsy. In particular, crawling and kneeling, and standing ability showed greater increases with intensive physical therapy. PMID- 27390439 TI - Propensity-matched analysis of the gap between capacity and actual performance of dressing in patients with stroke. AB - [Purpose] Dressing is an activity of daily living for which stroke patients often show discrepancies between capacity and actual performance. The aim of this study was to elucidate the physical function and unilateral spatial neglect in stroke patients that reduce their level of actual performance despite having the capacity for dressing independently. [Subjects and Methods] This retrospective study included 60 first-time stroke patients judged by occupational therapists as able to dress independently. The patients were divided into two groups according to their FIM((r)) instrument scores for dressing the upper and lower body: an independent group with both scores >=6 and an assistance group with one or both scores <=5. After adjusting for confounding factors through propensity score matching, the groups were compared by using Stroke Impairment Assessment Set items, the Simple Test for Evaluating Hand Function of both upper limbs, and the Berg balance scale. [Results] The assistance group had a significantly lower score for the Berg balance scale than the independent dressing group (31.0 +/- 12.3 vs. 47.8 +/- 7.4). [Conclusion] The results of the present study suggested that the balance function has an effect on the discrepancy between dressing capacity and performance. PMID- 27390441 TI - Effects of aerobic exercise intervention on serum cartilage oligomeric matrix protein levels and lymphocyte dna damage in obese elderly females. AB - [Purpose] The aim of the reported research was to investigate the effects of regular aerobic exercise on cartilage oligomeric matrix protein and oxidative DNA damage in obese, elderly females. [Subjects and Methods] Sixteen class I obese, elderly females, according to World Health Organization criteria, were randomly and equally assigned to a control group (n=8) or an exercise group (n=8). The exercise group participated in exercise sessions of 60 minutes per day, 3 days per week, for a period of 8 weeks. [Results] After aerobic exercise intervention, weight, body mass index, body fat, waist circumference, and DNA damage (Tail moment) were significantly decreased, compared with baseline values. In contrast, serum cartilage oligomeric matrix protein levels were not significantly different among any groups or time-points. [Conclusion] Regular aerobic exercise may be effective for reducing obesity-induced high DNA damage levels in obese females, without causing the deformation or degradation of lower extremity articular cartilage. PMID- 27390442 TI - The effect of lumbar stabilization exercise on the pulmonary function of stroke patients. AB - [Purpose] This study was aimed at assessing the effect of lumbar stabilization exercise on the pulmonary function of stroke patients. [Subjects and Methods] The subjects were randomly allocated into lumbar stabilization exercise group and a general physical therapy group. The program consisted of 30-min sessions conducted 3 days a week for 8 weeks. Pulmonary function was assessed based on lung performance parameters, including forced vital capacity, forced expiratory volume at 1 second, ratio of forced expiratory volume at 1 second to forced vital capacity, and peak expiratory flow. [Results] In the assessment of pulmonary function, the values of all the lung performance parameters were significantly increased in the lumbar stabilization exercise group but were significantly decreased in the general physical therapy group. [Conclusion] These results indicate that lumbar stabilization exercise had a more positive effect on pulmonary function than general physical therapy. PMID- 27390443 TI - Therapeutic efficacy of walking backward and forward on a slope in normal adults. AB - In this study, the therapeutic effects of backward walking were examined. [Subjects and Methods] In all, 16 subjects were randomly assigned to an experimental group and 17 to a control group. All subjects walked barefoot on a treadmill (HM50EX, Daeho, Korea) for 20 min, five times per week, for a total of 4 weeks. The average gait velocity of the subjects was 3 km/h on a 10% slope. The experimental group walked backwards and the control group walked forwards. [Results] The experimental group showed significant increments in both medial lateral and anterior-posterior balance, step length, and velocity compared with the pre-intervention results. In addition, the control group showed significant increments in anterior-posterior balance and velocity compared to the pre intervention results. Significant differences in post-training gains in anterior posterior balance, step length, and velocity were observed between the experimental and control groups. [Conclusion] Backward walking positively affected gait and balance ability after intervention. PMID- 27390444 TI - A comparative study of the effects of trunk exercise program in aquatic and land based therapy on gait in hemiplegic stroke patients. AB - [Purpose] The purpose of this study was to compare the effects of aquatic and land-based trunk exercise program on gait in stroke patients. [Subjects and Methods] The subjects were 28 hemiplegic stroke patients (20 males, 8 females). The subjects performed a trunk exercise program for a total of four weeks. [Results] Walking speed and cycle, stance phase and stride length of the affected side, and the symmetry index of the stance phase significantly improved after the aquatic and land-based trunk exercise program. [Conclusion] These results suggest that the aquatic and land-based trunk exercise program may help improve gait performance ability after stroke. PMID- 27390446 TI - Correlations between the sequelae of stroke and physical activity in Korean adult stroke patients. AB - [Purpose] The present study investigated a wide range of stroke patients living in South Korea using the Korean Community Health Survey raw data to determine the correlation between stroke and physical activity. [Subjects and Methods] This study used raw data from the 2012 Korean Community Health Survey. The total number of participants was 228,921; of the 4,475 stroke patients who had been diagnosed by a medical doctor or an oriental medical doctor, the data for 4,460 patients, excluding 15 whose amount of physical activity was unclear, were used in the analysis. [Results] The amount of physical activity performed by patients who had sequelae was significantly lower than that performed by patients who no longer had sequelae. Similarly, for the type of sequelae, palsy in the arms and legs, facial palsy, communication disability, swallowing or eating disability, and visual disability were associated with lower physical activity. Furthermore, as the number of sequelae increased, patients performed significantly less physical activity. [Conclusion] The findings suggest that when decisions on national policies and budgets are made, methods for increasing the physical activity of patients with a history of stroke should be considered. PMID- 27390445 TI - Comparison of timing and force control of foot tapping between elderly and young subjects. AB - [Purpose] To examine the ability of young and elderly individuals to control the timing and force of periodic sequential foot tapping. [Subjects and Methods] Participants were 10 young (age, 22.1 +/- 4.3 years) and 10 elderly individuals (74.8 +/- 6.7 years) who were healthy and active. The foot tapping task consisted of practice (stimulus-synchronized tapping with visual feedback) and recall trials (self-paced tapping without visual feedback), periodically performed in this order, at 500-, 1,000-, and 2,000-ms target interstimulus-onset intervals, with a target force of 20% maximum voluntary contraction of the ankle plantar flexor muscle. [Results] The coefficients of variation of force and intertap interval, used for quantifying the steadiness of the trials, were significantly greater in the elderly than in the young individuals. At the 500-ms interstimulus onset interval, age-related effects were observed on the normalized mean absolute error of force, which was used to quantify the accuracy of the trials. The coefficients of variation of intertap interval for elderly individuals were significantly greater in the practice than in the recall trials at the 500- and 1,000-ms interstimulus-onset intervals. [Conclusion] The elderly individuals exhibited greater force and timing variability than the young individuals and showed impaired visuomotor processing during foot tapping sequences. PMID- 27390447 TI - Comparison of trunk acceleration ratios during stair negotiation in old-old females. AB - [Purpose] This study compared trunk acceleration ratios in old-old adult females during stair negotiation. [Subjects and Methods] Twelve old-old adult females who could walk independently volunteered for this study. This study measured gait time and trunk acceleration ratios using an accelerometer during ascending and descending stairs [Results] The trunk acceleration ratio when descending stairs was significantly higher than that when ascending stairs. [Conclusion] These findings suggest that old-old females have greater deterioration of upper trunk control function for descending than for ascending stairs, regardless of task time. In addition, the trunk acceleration ratio during stair negotiation is a useful clinical marker to predict function and balance control ability in old-old females. PMID- 27390448 TI - Electromyographic analysis of an ergonomic risk factor: overhead work. AB - [Purpose] Repetitive upper extremity exercises result in overuse injuries. However, it is challenging to identify the specific causative movements. This study evaluated the effects of different shoulder positions on grip and electrophysiological activity of upper extremity muscles. [Subjects and Methods] Forty subjects ranging from 18 and 30 years of age were analyzed. Surface electromyography and hand grip strength were measured during a range of shoulder exercises and numerous signal processing methods were applied. [Results] The maximum electromyographic activity intensity was observed in the wrist extensors at various angles. Deltoid activity rose significantly during shoulder flexion. [Conclusion] Overhead work causes shoulder muscle fatigue and prevents effective hand function, which affects occupational health and efficiency. Overhead work involves a hazardous position and decreases efficiency. Ergonomic solutions should be developed to prevent muscle fatigue and decreased grip force. PMID- 27390449 TI - Comparison of vertebral and femoral bone mineral density in adult females. AB - [Purpose] This study assessed vertebral and femoral bone mineral density in adult females. [Subjects and Methods] A total of 314 females in their 40s to 70s were divided into normal, osteopenia, and osteoporosis groups and their vertebral and femoral bone mineral densities were compared. [Results] Comparisons of T scores revealed significant differences among measurements of the third lumbar vertebra, femoral neck, Ward's triangle, and femoral trochanter. Pearson correlation coefficients were used to assess differences between the vertebral and femoral measurements, and significant differences and positive correlations were observed among third lumbar vertebra, femoral neck, Ward's triangle, and femur trochanter in the normal group. [Conclusion] Females in the normal, osteopenia, and osteoporosis groups showed significant differences in their third lumbar vertebrae. The lack of significant differences among measurements in the osteoporosis group in this study suggests that patients with osteoporosis require careful and accurate diagnosis. PMID- 27390450 TI - Effects of movement from a postural maintenance position on lumbar hemodynamic changes. AB - [Purpose] To investigate the effects of movement from a postural maintenance position on lumbar hemodynamic changes, in order to prevent lower back pain and develop exercise therapy. [Subjects and Methods] Twenty-five healthy adults (mean age: 23.2 years) participated in the study. During flexion-extension exercise, the subjects moved their trunks gradually to a flexed position from an upright posture while sitting and standing, and then returned to and maintained an upright (re-upright) position. In the extension-flexion exercise, the subjects moved their trunks gradually from an upright posture to an extended position, and back while maintaining an upright (re-upright) position. Lumbar spinal muscle activity and hemodynamic changes were evaluated during both exercises. [Results] During the flexion and extension exercises, increased trunk-flexion angle caused increased muscle activity, decreased oxygenated hemoglobin in the multifidus muscle, and increased deoxygenated hemoglobin in the multifidus and lumbar erector spinae muscles. Moreover, the muscle activities were nearly the same in the re-upright and upright positions, and total hemoglobin also increased. [Conclusion] In both standing and sitting positions, holding the trunk in a flexed position causes ischemic hemodynamic changes in the multifidus muscle; however, the hyperemic response when returning the trunk to an extended position may improve circulation. PMID- 27390451 TI - Measures used for the evaluation of balance in individuals with Parkinson's disease: a systematic review. AB - [Purpose] The present literature review was conducted on the use of different measures for the evaluation of balance in patients with Parkinson's disease. [Materials and Methods] The PubMed, Bireme, SciELO, Lilacs, and PEDro electronic databases were searched for relevant studies. [Results] The searches initially led to the retrieval of 3,623 articles, 540 of which were potentially eligible after limiting the search to clinical trials published in the last five years. A total of 264 duplicates were removed, and 276 articles were excluded based on their titles and abstracts. The full texts of 84 articles were analyzed, and only those with a PEDro score higher than four points (n=25) were included in the review. [Conclusion] Different methods, such as scales, tests, and equipment, are used for the evaluation of balance in patients with Parkinson's disease. More than one measure has been employed in most studies, and there is no consensus on a single precise measure for the evaluation of balance in this population. PMID- 27390452 TI - Mesenchymal stem cells in regenerative rehabilitation. AB - [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient's medical status. The intrinsic self renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID- 27390453 TI - Clinical usefulness of Adeli suit therapy for improving gait function in children with spastic cerebral palsy: a case study. AB - [Purpose] The purpose of this study was to determine the effects of Adeli suit therapy (AST) on gross motor function and gait function in children with cerebral palsy. [Subjects and Methods] Two participants with spastic cerebral palsy were recruited to undergo AST. AST was applied in 60-minute sessions, five times per week, with 20 sessions total over 4 weeks. Assessments of gross motor function, spatiotemporal parameters, and functional ambulation performance for gait were conducted. [Results] Gross motor function, cadence, and functional ambulation performance improved after the intervention in both cases. [Conclusion] Although additional follow-up studies are required, the results demonstrated improved gross motor function and functional ambulation performance in the children with cerebral palsy. These findings suggest a variety of applications for conservative therapeutic methods that require future clinical trials in children with cerebral palsy. PMID- 27390454 TI - Postoperative nutrition practices in abdominal surgery patients in a tertiary referral hospital Intensive Care Unit: A prospective analysis. AB - BACKGROUND: Benefit of early enteral feeds in surgical patients admitted to Intensive Care Units (ICUs) has been emphasized by several studies. Apprehensions about anastomotic leaks in gastrointestinal surgical patients prevent initiation of early enteral nutrition (EN). The impact of these practices on outcome in Indian scenario is less studied. AIMS: This study compares the impact of early EN (within 48 h after surgery) with late EN (48 h postsurgery) on outcomes in abdominal surgical ICU patients. SETTINGS AND DESIGN: Postabdominal surgery patients admitted to a tertiary referral hospital ICU over a 2-year period were analyzed. METHODS: Only patients directly admitted to ICU after abdominal surgery were included in this study. ICU stay>3 days was considered as prolonged; with average ICU length of stay (LOS) for this ICU being 3 days. The primary outcome was in-patient mortality. ICU LOS, hospital LOS, infection rates, and ventilator days were secondary outcome measures. Acute Physiology and Chronic Health Evaluation II scores were calculated. SPSS and Microsoft Excel were used for analysis. RESULTS: Of 91 ICU patients included, 58 received early EN and 33 late EN. Hospital LOS and infection rates were less in early EN group. Use of parenteral nutrition (odds ratio [OR] 5.25, 95% confidence interval (CI); P = 0.003) and number of nil-per-oral days (OR 8.25, 95% CI; P <= 0.001) were other predictors of prolonged LOS. CONCLUSIONS: Early EN in postabdominal surgery ICU patients was associated with reduced hospital LOS and infection rates. ICU LOS, duration of mechanical ventilation and mortality rates did not vary. PMID- 27390456 TI - Acute kidney injury-incidence, prognostic factors, and outcome of patients in an Intensive Care Unit in a tertiary center: A prospective observational study. AB - BACKGROUND AND AIMS: The information regarding the incidence of acute kidney injury (AKI) in medical Intensive Care Units (ICUs) in South India is limited. The aim of the study was to find the incidence, prognostic factors, and outcome of patients with AKI. We also assessed whether only urine output criteria of risk, injury, failure, loss, end (RIFLE) classification can be used to look at the outcome of AKI. PATIENTS AND METHODS: This was a prospective, cross-sectional study of 6 months duration in a 28 bedded medical ICU of a tertiary center. AKI was defined as an absolute creatinine value of>1.6 mg/dl or a 25% increase from baseline creatinine values. RESULTS: The incidence of AKI was 16.1%, and mortality was 7.8% in our study population. Among patients with AKI 87 (75.7%) patients had sepsis. 71.3% patients had metabolic acidosis on admission, and 47.8% patients were in shock. 57.4% of patient's required mechanical ventilation (MV). 39.1% of AKI patients required renal replacement therapy (RRT). Requirement of RRT was significantly affected by increasing age, Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores on admission, serum creatinine, and use of vasopressors. 49.5% of patients with AKI died within 28 days. Increasing age, MV, hemodialysis (HD), hypertension, chronic kidney disease, and requirement of noradrenaline support were associated with increasing 28 days mortality. The maximum RIFLE score with urine output criteria showed association to the requirement of HD in univariate analysis but did not show relation to mortality. CONCLUSION: The incidence of AKI was 16.1% in critically ill patients. In patients with AKI, 39.1% patients required HD and 28 days mortality was 49.5%. The study also showed good univariate association of urine output criteria of RIFLE classification to the requirement of HD in AKI patients. PMID- 27390455 TI - Sleep after critical illness: Study of survivors of acute respiratory distress syndrome and systematic review of literature. AB - BACKGROUND AND AIMS: This study aims to evaluate the sleep quality, architecture, sleep-related quality of life, and sleep-disordered breathing (SDB) in acute respiratory distress syndrome (ARDS) survivors early after discharge. MATERIALS AND METHODS: In this prospective, observational study, consecutive patients with ARDS discharged from the Intensive Care Unit (ICU) underwent evaluation with Epworth sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), and overnight polysomnography. Patients having one or more of the following characteristics were classified as having abnormal sleep: ESS>10, PSQI>5, FOSQ <17.9, apnea-hypopnea index (AHI) >=5, or AHI during rapid eye movement (REM) sleep >=5. RESULTS: Twenty patients (median interquartile range [IQR] age of 24 [22-28] years, 11 [55%] females) were included in the study. Acute febrile illness of unknown etiology with multi-organ dysfunction syndrome was the most common underlying etiology for ARDS. The median (IQR) PaO2/FiO2 ratio and APACHE II scores on admission were 176 (151-191.5) and 14 (14-16), respectively. The median (IQR) duration of stay in the ICU was 10 days (7.3-19.5). The overall sleep efficiency (median [IQR], 54% [32.3-65.4%]) was poor. None of the patients had ESS>10, seven (35%) had global PSQI>5 and one had FOSQ <17.9. Ten (50%) patients had at least one characteristic that suggested abnormal sleep (4 insomnia, 2 central sleep apnea, 1 obstructive sleep apnea, 1 REM-SDB, and 2 with a high PSQI, but no specific sleep abnormality). CONCLUSIONS: Sleep disturbances are common in ARDS survivors early after discharge from the ICU. PMID- 27390457 TI - Mobilization of patients in neurological Intensive Care Units of India: A survey. AB - CONTEXT: The rehabilitation needs of the patients in neurological Intensive Care Units (ICUs) vary from that of a medical ICU patient. Early mobilization is known to improve the various neurological outcomes in patients admitted to neurological ICUs, although little is known about the practice pattern among physiotherapists. The mobilization practice pattern may vary significantly than that of developed countries due to the reasons of differences in training of professionals, availability of equipment, and financial assistance by health insurance. AIM OF THE STUDY: To study the current mobilization practices by the physiotherapists in neurological ICUs of India. SUBJECTS AND METHODS: A cross-sectional survey was conducted with a content validated questionnaire about the mobilization practices. Online questionnaire was distributed to physiotherapists working in neurological ICUs of India. Descriptive statistics were used. RESULTS: Out of 185 e-mails sent, 82 physiotherapists completed the survey (survey response rate = 44%). Eighty participants (97.6%) mentioned that the patients received some form of mobilization during the day. The majority of the physiotherapists (58.5%), "always" provided bed mobility exercises to their patients when it was found appropriate for the patients. Many physiotherapists (41.5%) used tilt table "sometimes" to introduce orthostatism for their patients. CONCLUSION: Mobilization in various forms is being practiced in the neurological ICUs of India. However, fewer mobilization sessions are conducted on weekends and night hours in Indian Neurological ICUs. PMID- 27390459 TI - Yakson touch as a part of early intervention in the Neonatal Intensive Care Unit: A systematic narrative review. AB - Yakson is a Korean therapeutic touch given to neonates and infants by caressing their abdomen with one hand while the other hand is placed on the back of the neonate?infant either to relieve their pain or to calm them down. It was traditionally used by Koreans by caressing the aching body part of their children with a belief that it would relieve their pain. In spite of clinical evidence of its usefulness, there is limited literature available on Yakson touch. A systematic narrative review (SNR) was undertaken on studies that were carried out on the effectiveness of Yakson touch on infants and neonates. Only seven studies were detected from five major electronic databases, searched with the keywords: "Yakson," "Yakson touch," and "Yakson in neonates". One of the studies has been included in two Cochrane reviews by the same group of researchers published in 2011 and 2015, respectively, and also in a literature review. The evidence from these articles suggests that Yakson touch is able to increase the sleep scores of infants, affects their behavioral response, decreases the stress levels, increases maternal attachment, and has calming effects on them. However, the number of studies is limited, and thus the efficacy of this intervention has not been sufficiently established. Hence, there is a definite need for future studies to prove the efficacy of Yakson to include it in the early intervention programs. This SNR is aimed at compiling the studies which determined to prove the efficacy of the intervention of Yakson. PMID- 27390458 TI - High frequency oscillatory ventilation in leptospirosis pulmonary hemorrhage syndrome: A case series study. AB - Hypoxemia in severe leptospirosis-associated pulmonary hemorrhage syndrome (LPHS) is a challenging clinical scenario not usually responsive to maximal support on mechanical ventilation. We described the efficacy and safety of high frequency oscillatory ventilation (HFOV) as rescue therapy in acute respiratory failure secondary to LPHS. This is a retrospective case study of five patients with diagnosis of severe LPHS, who were admitted to Intensive Care Unit from October 2014 to January 2015. They developed refractory hypoxemia on conventional mechanical ventilation and rescue therapy was indicated. All patients responded rapidly by showing improvements in oxygen index and PaO2/FiO2 ratio within first 72 h of therapy. Despite severity of illness evidenced by high Simplified Acute Physiological II and Sequential Organ Failure Assessment scores, all patients were discharged from hospital alive. In view of the rapid onset and extent of hemorrhage which may culminate quickly into asphyxiation and death, HFOV may indeed be lifesaving in severe LPHS. PMID- 27390460 TI - The risk factors of colistin methanesulfonate associated nephrotoxicity. AB - PURPOSE: The risk factors of colistin methanesulfonate (CMS) associated nephrotoxicity are important. Our study attempts look into the prevalence of CMS associated nephrotoxicity in Intensive Care Units (ICUs), and related risk factors. MATERIALS AND METHODS: The study was conducted between September 2010 and April 2012 on 55 patients who underwent CMS treatment. Nephrotoxicity risk was defined based on the Risk Injury Failure Loss End-stage kidney disease criteria. RESULTS: Fifty-five patients included in the study. A total of 22 (40%) patients developed nephrotoxicity. The correlation was detected between nephrotoxicity and patients over 65 with a high Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score. APACHE II score was revealed an independent risk factor for nephrotoxicity. CONCLUSION: Advanced age and a high APACHE II score are significant risk factors in the development of nephrotoxicity at ICUs following CMS use. Patient selection and close monitoring are critical when starting CMS treatment. PMID- 27390461 TI - Bedside placement of small-bowel feeding tube in Intensive Care Unit for enteral nutrition. AB - Enteral nutrition is the preferred mode of nutrition in critically ill patients whenever feasible as it has a number of advantages over parenteral feeding. Both gastric and small-bowel feeding can effectively deliver calories. In patients with gastroparesis, small-bowel feeding can help avoid parenteral feeding. We carried out a retrospective observational study to assess the ability to insert the Tiger 2 tube into the small bowel at the bedside in 25 patients who failed to tolerate gastric feeds. The time taken, rate of successful insertion, and ability to feed these patients using a standardized feeding protocol were noted. Success rate of insertion was 78% and feeding could be established. This method reduced the delays and risks associated with transportation and dependence on other specialties. PMID- 27390462 TI - Panayiotopoulos syndrome in a child masquerading as septic shock. AB - Panayiotopoulos syndrome (PS) is a benign childhood epilepsy with predominant autonomic symptoms. The syndrome can have varied presentations resulting in diagnostic dilemma. We herein describe a 3-year-old boy with PS, who had manifestations similar to septic shock. His investigations were normal and had a complete recovery. Through this case, we wish to highlight the unusual presentation of PS as septic shock. Physicians should be aware of the different ways in which this syndrome can present to ensure its early diagnosis and treatment. PMID- 27390463 TI - Neurally adjusted ventilation assist in weaning difficulty: First case report from India. AB - Invasive mechanical ventilation is an integral component in the management of critically ill patients. In certain situations, liberation from mechanical ventilation becomes difficult resulting in prolonged ventilation. Patient ventilator dyssynchrony is a frequently encountered reason for difficult weaning. Neurally adjusted ventilatory assist (NAVA) is a novel mode of ventilation that utilizes the electrical activity of diaphragm to pick up respiratory signals and delivers assistance in proportion to the ventilatory requirement of a patient. It may, therefore, be associated with a better patient-ventilator synchrony thereby facilitating weaning. Herein, we report the first case from India describing the use of NAVA in successfully weaning a patient with difficult weaning. PMID- 27390464 TI - Successful management of zinc phosphide poisoning. AB - Zinc phosphide (Zn2P3) rodenticide, is generally misused intentionally for suicidal purpose in Iran. For many years, scientists believe that liberation of phosphine (PH3) on contact with acidic content of the stomach is responsible for clinical presentations. However, relatively long time interval between ingestion of Zn2P3 and presentation of its systemic toxicity, and progression of acute liver failure could not be explained by the current opinion. Hence, an innovative theory intended that phosphonium, as an intermediate product will create and pass through the stomach, which then will reduce to produce PH3in the luminal tract. Here, we present a case of massive Zn2P3 poisoning. In our case, we used repeated doses of castor oil to induce bowel movement with an aim of removing unabsorbed toxin, which was proved by radiography. Interestingly, the patient presents only mild symptoms of toxicity such as transient metabolic acidosis and hepatic dysfunction. PMID- 27390465 TI - Clinically HIV but negative serology: Think of idiopathic CD4(+) lymphocytopenia. AB - idiopathic CD4(+) lymphocytopenia (ICL) is a rare disorder characterized by the presence of depleted CD4 cell line without the presence of HIV infection. Slight male preponderance is noticed and is usually seen in the middle age group. Opportunistic infections are the reason for their discovery and here we describe a case where a man was diagnosed as having Pneumocystis jiroveci pneumonia and oral candidiasis. PMID- 27390466 TI - Thrombotic microangiopathy as an initial manifestation in HIV patients. AB - Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, microvascular thrombosis, and various organ dysfunctions. TMA usually occurs in a more advanced stage of HIV disease. TMA as an initial presenting feature is rare. We here report a male patient who presented with oliguric renal failure. Investigations revealed anemia, thrombocytopenia, schistocytes in peripheral smear, and HIV-positive. Renal biopsy revealed TMA. He was treated with hemodialysis and started on highly active antiretroviral therapy. PMID- 27390467 TI - Esophageal pressure-guided positive end-expiratory pressure in acute respiratory distress syndrome: The jury is still out! PMID- 27390468 TI - Procedural improvisation to prevent guidewire kinking in Griggs percutaneous tracheostomy without bronchoscopic guidance. PMID- 27390469 TI - Keep an eye on Murphy's eye during percutaneous dilatational tracheostomy. PMID- 27390470 TI - Hyperthermia and malfunction of transesophageal echocardiographic probe. PMID- 27390471 TI - The revised guidelines of the Medical Council of India for academic promotions: Need for a rethink. PMID- 27390472 TI - Mobile phone use and possible cancer risk: Current perspectives in India. AB - Mobile communication is now essentially ruling our daily lives through better connectivity and intelligent smartphone services. There has been a tremendous growth in Indian communication industry along with growing concerns regarding health effects of mobile radiation exposure. Concerns posed are especially regarding carcinogenesis and other health-related effects of mobile radiation exposure. In the effort to establish or refute any such concerns, many studies have been undertaken in the past three decades, mostly case-control designs or cross-sectional surveys. However, most of them considerably failed to establish causal association primarily owing to potential biases and errors in their conduct and analysis. Past cohort studies have provided contradictory results leading to continued uncertainty regarding tumorigenic potential of mobile radiation exposure. In India, there remains a huge knowledge gap pertaining to this particular topic and only few studies are presently underway such as the Indian Council of Medical Research (ICMR) cell phone study in the National capital region (NCR). International Agency for Research on Cancer (IARC) has classified radiofrequency electromagnetic fields associated with wireless phone use as possibly carcinogenic to humans (Group 2B), causing major concerns worldwide among mobile companies and subscribers equivocally. The World Health Organization (WHO) is presently carrying formal risk assessment of all studied health outcomes from radio frequency field's exposures and is likely to publish it by the year 2016. PMID- 27390473 TI - Impact of social determinants on well-being of urban construction workers of Hyderabad. AB - BACKGROUND: Hyderabad has witnessed one of the largest labor immigration in recent years and these construction workers are highly vulnerable in terms of health. Social determinants of health (SDH) arise from conditions in which they live and these factors interact with each other to produce direct impact on health. OBJECTIVES: (1) To evaluate the sociodemographic and job characteristics of the construction workers. (2) To assess the impact of social determinants on well-being. MATERIALS AND METHODS: A sample size of 135 construction workers working at three sites of HITEC city were interviewed using semi-structured questionnaire. Health perception and the impact on well-being was measured using the Healthy Days Module and Kessler's Psychological Distress Scale. SDH were measured on a 27-item questionnaire with responses on a Likert scale ranging from 0 to 4. Proportions, percentages, P values, and mean scores were obtained. RESULTS: The mean age of the sample was 35.4 +/- 11.94 years. Seventeen (12.6%) of the workers reported a high risk score on the Kessler's Psychological Distress Scale. Binary logistic regression analysis was used to identify significant domains of social determinants independently associated with the well being of construction workers and significant among the nine domains of social determinants were addiction score domain with odds of 2.259 and a P value of 0.015 and the distress domain with odds of 1.108 and a P < 0.001. CONCLUSIONS: There is a significant impairment of physical and mental health due to various factors including SDH, such as addictive habits and psychological distress, which are amenable to prevention. PMID- 27390474 TI - Chronic disease risk factors among hotel workers. AB - CONTEXT: Non-communicable diseases have emerged as a global health issue. Role of occupation in pathogenesis of non-communicable diseases has not been explored much especially in the hospitality industry. AIMS: Objectives of this study include finding risk factor prevalence among hotel workers and studying relationship between occupational group and chronic disease risk factors chiefly high body mass index. SETTINGS AND DESIGN: A cross-sectional study was conducted among non-managerial employees from classified hotels in India. MATERIALS AND METHODS: The study participants self-administered pre-designed pilot-tested questionnaires. STATISTICAL ANALYSIS USED: The risk factor prevalence rates were expressed as percentages. Chi-square test was used for bi-variate analysis. Overweight was chosen as 'outcome' variable of interest and binary multi-logistic regression analysis was used to identify determinants. RESULTS: The prevalence rates of tobacco use, alcohol use, inadequate physical activity and inadequate intake of fruits and vegetables were 32%, 49%, 24% and 92% respectively among hotel employees. Tobacco use was significantly common among those in food preparation and service, alcohol use among those in food service and security and leisure time physical activity among front office workers. More than two-fifths (42.7%) were overweight. Among the hotel workers, those employed in food preparation and security had higher odds of 1.650 (CI: 1.025 - 2.655) and 3.245 (CI: 1.296 - 8.129) respectively of being overweight. CONCLUSIONS: Prevalence of chronic disease risk factors is high among hotel workers. Risk of overweight is significantly high in food preparation and security departments and workplace interventions are necessary to address these risks. PMID- 27390475 TI - Assessment of occupational radiation exposure among medical staff in health-care facilities in the Eastern Province, Kingdom of Saudi Arabia. AB - INTRODUCTION: Radiation exposure poses hazards for health-care providers as well as patients in health-care facilities (HCFs). Radiographic imaging is extremely valuable as a diagnostic tool in medicine, but ionizing radiation and computed tomography (CT) scan carry well-known potential risks. Personnel and radiation safety monitoring is an important safety precaution in the practice of radiography. AIM: The study aimed to assess the occupational radiation exposure and safety protection among medical staff in HCFs in the Eastern Province, Kingdom of Saudi Arabia (KSA). MATERIALS AND METHODS: Total of 4 HCFs with radiological services were randomly selected for the study in the period from January to April 2013. The radiation survey has been carried out by the measurement of radiation in the x-ray and CT-scan room at different points of the diagnostic, imaging, and waiting rooms of different hospitals. The radiation safety was assessed by using a questionnaire. RESULTS: The results of our study are surprising and alarming. Data revealed that there are a significant association between the levels of radiation exposure in all selected hospitals concerning imaging and waiting X-ray and CT-scan operating room (P < 0.01). For radiation safety, most hospitals have lead aprons and thyroid shields in place, but only about 50% have lead glasses and lead shields, showing that many hospitals still lack essential equipment. Moreover, actual utilization rate of radiation dosimeters are 57.7% and 68.9%, respectively. CONCLUSION: All medical staff as well as patients are at risk of exposure to x-ray and CT-scan radiation exposure, and the levels are exceeding the standard guidelines. Many hospitals still lack safety protection tools and there is a complete absence of radiation protection equipment. Further studies should be conducted to highlight different aspects of radiation exposure dose and safety protection tools. PMID- 27390476 TI - Comparative cross-sectional study for understanding the burden of low back pain among public bus transport drivers. AB - BACKGROUND: Even though low back pain (LBP) is common, some occupations pose a higher risk. Identifying these occupations and specific factors will help to reduce the suffering and burden. This study aims to compare the prevalence of chronic LBP among bus drivers and to find its association with some occupational factors. MATERIALS AND METHODS: It is a cross-sectional study to compare prevalence of LBP and factors associated with it, in two groups of drivers (n = 178) and nondrivers (n = 184). RESULTS: The 10 years' percentage prevalence of LBP was found to be 70.8 and 51.6 among drivers and nondrivers respectively, whereas point prevalence in the same was 64.0 and 44.6. Drivers are at a higher risk for LBP with Odds ratio-2.270 (1.471-3.502). Risk factors such as prolonged sitting in one posture, night shifts, job dissatisfaction, tobacco use, and lack of exercise were significantly higher among drivers. Though the prevalence and intensity of LBP was higher among drivers, their number of leaves and hospital admitted days were less among drivers. CONCLUSION: This is a potential group for intervention as prevalence of LBP, neck pain, and most of the suspected risk factors were higher among the drivers. Drivers got less recovery time and had higher sequelae. PMID- 27390477 TI - Effectiveness of video-assisted teaching program on safety measures followed by the employees working in the silica-based industry in Puducherry, India. AB - INTRODUCTION: Employees constitute a large and important sector of the world's population. The global labor force is about 2,600 million and 75% of this force is working in developing countries. Occupational health and safety (OHS) must be managed in every aspect of their work. Occupational safety and health (OSH), also commonly referred to as OHS or workplace health and safety (WHS) is an area concerned with the safety, health, and welfare of people engaged in any employment. The goal of OSH is to foster a safe and healthy work environment. The aim of this study is to evaluate the effectiveness of video-assisted teaching program on safety measures. MATERIALS AND METHODS: A total of 105 employees were selected from M/s ACE Glass Containers Ltd. at Puducherry, India using the convenience sampling technique. Pretest was conducted using a self-administered questionnaire. Subsequent video-assisted teaching was conducted by the investigator after which posttest was conducted. RESULTS AND CONCLUSION: Video assisted teaching program was found to be effective in improving the knowledge, attitude, and practice of the subjects. Periodical reorientation on safety measures are needed for all the employees as it is essential for promoting the well-being of employees working in any industry. PMID- 27390478 TI - Shift work disorder and related health problems among nurses working in a tertiary care hospital, Bangalore, South India. AB - INTRODUCTION: Shift Work Disorder (SWD) is a sleep disorder characterized by sleepiness and insomnia, which can be attributed to the person's work schedule. Awareness of the mechanisms behind shift work related health problems could be essential to schedule the shift work, employment routines, clinical treatment, and selection of employees. OBJECTIVE: To assess the prevalence of SWD and to identify related health problems among nurses in a tertiary care hospital in Bangalore. MATERIALS AND METHODS: We conducted a descriptive cross-sectional study in a tertiary care hospital in Bangalore between May and September 2014. Based on simple random sampling, 130 nurses were selected for the study. After obtaining written informed consent from the participants, structured interview schedule using Standard Shift Work Index and Bergen Shift Work Sleep Questionnaire (BSWSQ) was administered. RESULTS: The mean age of the 130 nurses was 27.4 +/- 2.64 years. The prevalence of SWD was found to be 43.07%. Headache, back pain, gastritis, and menstrual disorders were the most common complaints, which are found in 78 (60.0%), 75 (57.6%), 42 (32.3%), and 39 (30.0%) cases, respectively. Anxiety and depression was found in 23 (17.6%) and 31 (23.8%) individuals, respectively. We also found a significant association of SWD with increasing age, more number of nights worked in a year, and longer duration of working hours. According to the BSWSQ, 70 (53.8%) nurses were found to have sleep problems. CONCLUSION: A high prevalence of SWD symptoms calls for a focus on the antecedents of work related sleep problems and appropriate intervention, such as behavioral changes, clockwise rotating shifts, and treatment. PMID- 27390479 TI - Staff working in ancillary departments at a tertiary care hospital in Bengaluru, Karnataka, India: How healthy are they? AB - BACKGROUND: Ancillary health services are those supplemental services other than room, board, and medical/nursing services provided to hospital patients in the course of care. Ancillary department staff forms an integral part in the smooth functioning of a hospital. There is a need to focus on the health of these individuals to ensure their well-being and in turn, productivity at the workplace. OBJECTIVE: To study the morbidity profile of the staff working at ancillary departments of a tertiary care hospital in Bengaluru, Karnataka, India. MATERIALS AND METHODS: We conducted our study in a 1,200-bedded tertiary care hospital in Bengaluru, Karnataka, India. Annual medical checkup (AMC) for all the staff working at the ancillary departments has been started in recent years and is provided free of cost and during working hours. A total of 150 employees from ancillary departments underwent AMC in the year 2013. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 20.0. Spearman's correlation and Chi-square test were used. RESULTS: Of the 150 employees, the majority was male (72%); the mean age was 38 +/- 11 years. The most common morbidities were diabetes mellitus (11%), hypertension (10.6%), musculoskeletal disorders (9.3%), surgical problems (8.6%, hemorrhoids, varicose veins), and dental caries (6.6%). On stool microscopy, 12% of the dietary workers showed ova/cyst. There was a significant positive correlation between age and the number of chronic morbidities (P < 0.01). CONCLUSION: Lifestyle disorders such as diabetes mellitus and hypertension were the major morbidities among the staff in the ancillary departments of the hospital. We ensured regular follow-up, adherence to medication, and lifestyle modifications in terms of diet and exercise. PMID- 27390480 TI - Comparison of workers' perceptions toward work climate and health symptoms between ceramic and iron foundry workers. AB - BACKGROUND: Workers exposed to heavy manual material handling (MMH) in a hot working environment succumb to severe physical stress and psychological stress. AIMS: (1) Recognize the heat load at workplaces of ceramic industry and iron industry, and (2) comparatively examine the characteristics of self-reported physiological responses and heat-health perception among these workers. SETTINGS AND DESIGN: Cross-sectional prospective study. MATERIALS AND METHODS: Workplace microclimate in the ceramic industry and iron industry was monitored. An ergonomic checklist and a questionnaire was used to record self-reported workers' perceptions toward heat stress at workplace (ceramic workers N = 321, iron foundry workers N = 253). The prevalence rates of subjective symptoms among workers of both the industries were compared. STATISTICAL ANALYSIS: Chi-square test was used to examine the association between stressors and health complaints at a significance level set at P < 0.05. RESULTS: Iron foundries recorded higher mean ambient temperature (43.4 +/- 3.7 degrees C) and wet-bulb globe temperature (WGBT) index (31.5 +/- 0.7 degrees C) as compared to ceramic industries (39.9 +/- 3.3 degrees C and 28 +/- 1.5 degrees C, respectively). Heavy sweating, elevated body temperature, sleeplessness, excessive thirst, muscular discomforts, and fatigue were prime symptoms recorded among workers of both industries. Skin related disorders (red face, dry skin, bumps, itching) were significantly higher among iron foundry workers, whereas sleeplessness, high blood pressure, heavy sweating, kidney stone, decreased urination, muscular discomforts, and fatigue were significantly more among ceramic workers. Young workers reported more sweating and fatigue than older workers. CONCLUSIONS: A hot work climate and heavy manual labor designate ceramic and iron industries as arduous. Direct contact with hot surface and continuous MMH in tandem with the mechanical pace of production process makes work in ceramic industries more difficult than iron foundries. PMID- 27390481 TI - Quality of life and probable psychological distress among male workers at a construction site, Kolar district, Karnataka, India. AB - INTRODUCTION: The construction industry, which mainly consists of migrant labouers is one of the largest employers in the unorganized sector in India. These workers work in poor conditions and are often vulnerable to exploitation. These workers also do not have health care benefits and often these factors lead to poor quality of life (QOL) and psychological distress. OBJECTIVES: To assess the QOL, probable psychological distress and associated factors among male construction workers. MATERIALS AND METHODS: A cross-sectional study was conducted between September 2013 and November 2013 among 404 male workers. These construction workers were enrolled by consecutive sampling at a construction area in Kolar district, Kaarnataka, India. The study tools used were World Health Organization (WHO) QOL-BREF and 12-Item General Health Questionnaire (GHQ-12) to assess QOL and probable psychological distress, respectively. The transformed scores in WHO QOL-BREF in all four domains ranged 0-100. The four domain scores are scaled in a positive direction with higher scores indicating a higher QOL. Associations were done using statistical tests such as Chi-square, correlation, regression, independent samples t-test, and analysis of variance (ANOVA). RESULTS: A total of 404 male workers with a mean age of 25.6 +/- 7.3 years were studied. Mean scores of various domains of QOL were 68.5 +/- 13.7 (physical), 59.9 +/- 13.5 (psychological), 64.3 +/- 16.4 (social), and 44.1 +/- 12.8 (environmental). On the self- rating scale, 59 (14.6%) workers were rated as having poor QOL. The prevalence of probable psychological distress was 27.5%. Factors such as increasing age, being currently married, and low educational status were found to be significantly associated (P < 0.05) with poor QOL and psychological distress. There was a significant negative correlation (P < 0.05) between QOL and psychological distress and a positive correlation between income and QOL. CONCLUSION: The QOL in the environmental domain, which mainly deals with living conditions, health, and recreational facilities was found to be poor and there was a high prevalence of probable psychological distress among workers. This indicates a need for improving workplace amenities, and access to health and recreational facilities. PMID- 27390482 TI - "Bright asteroids in the polar sky"-clinic-radio-pathological correlation in an unusual case of silicotuberculosis. AB - We present a case of acute silicosis presenting with severe breathlessness and respiratory failure. An unusual aspect in our case was the presence of acute silicosis with respiratory failure in backdrop of long-term silica exposure. The other striking aspect in this case was the demonstration of crystalline silica particles under polarizing light in bronchial lavage fluid sample and coexistence of tuberculosis with acute silicosis. PMID- 27390484 TI - Sustainable sanitation in India: Need of the hour. PMID- 27390483 TI - High prevalence of cardiometabolic risk factors in young employees of Information Technology industry. AB - BACKGROUND: We assessed the burden of cardiometabolic risk factors in Information Technology (IT) employees as they are exposed to adverse lifestyle. MATERIALS AND METHODS: In this cross-sectional study, health records were obtained from two IT industries in Pune. Prevalence of cardiometabolic risk factors [hyperglycemia, high blood pressure (BP), hypertriglyceridemia, high low-density lipoprotein (LDL)-cholesterol, low high-density lipoprotein (HDL)-cholesterol, and overweight/obesity] was determined using standard cutoffs. We also examined clustering of risk factors (>=two risk factors). RESULTS: Data were available on 1,350 of 5,800 employees (mean age: 33 +/- 6 years, 78% men). Prevalence of diabetes and hypertension was 2.5% and 13.5%, respectively. Prevalence of prediabetes, borderline high BP, hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, and overweight/obesity was 6.5%, 20.3%, 21%, 22.1%, 70.1%, and 51.4%, respectively. Risk factor clustering was observed in 63.5% that increased with age (P < 0.001). CONCLUSION: Given the high burden of risk factors at relatively young age, spreading awareness and promoting healthy lifestyle through workplace interventions are warranted. PMID- 27390485 TI - Distraction histogenesis: The way ahead. PMID- 27390487 TI - Accidental aspiration/ingestion of foreign bodies in dentistry: A clinical and legal perspective. AB - The potential of foreign body aspiration or ingestion is a worldwide health problem in dentistry. The general dental practitioners should be extremely attentive in handling of minor instruments during any intervention related to the oral cavity, especially in the supine or semi-recumbent position of the patient. Aspiration cases are usually more critical and less common than ingestion. We report a case of iatrogenic aspiration of an endodontic broach, which gets disclosed during the recording of past dental history of the patient. The patient was asymptomatic during that time. A quick posterior-anterior chest radiograph was taken which revealed the presence of broach in the lower lobe of the left lung. The patient was immediately referred to the pulmonary medicine department where the fiberoptic bronchoscope retrieval was planned, and the same was carried out successfully under local anesthesia. Although such accidents have rare occurrence, the associated risks and morbidity are too high to be overlooked, especially from the viewpoint of special care, resources, and the associated financial cost required for their management. Moreover, practitioners are also liable for malpractice litigation given the fact that such cases are avoidable. This article also discusses relevant review literature, risk factors, symptoms, and management of such iatrogenic accidents along with drawing attention to the significance of preventive measures and their role in avoiding meritorious legal and ethical issues. PMID- 27390486 TI - A review of complications of odontogenic infections. AB - Life-threatening infections of odontogenic or upper airway origin may extend to potential spaces formed by fascial planes of the lower head and upper cervical area. Complications include airway obstruction, mediastinitis, necrotizing fascitis, cavernous sinus thrombosis, sepsis, thoracic empyema, Lemierre's syndrome, cerebral abscess, orbital abscess, and osteomyelitis. The incidence of these "space infections" has been greatly reduced by modern antibiotic therapy. However, serious morbidity and even fatalities continue to occur. This study reviews complications of odontogenic infections. The search done was based on PubMed and Google Scholar, and an extensive published work search was undertaken. Advanced MEDLINE search was performed using the terms "odontogenic infections," "complications," and "risk factors." PMID- 27390488 TI - Applications of botulinum toxin in dentistry: A comprehensive review. AB - The horizons of treatment options in dentistry are broadening rapidly. In this scenario, applications of unconventional treatment options like use of botulinum toxin (BT) are gaining momentum. The use of BT has been popularly accepted in esthetic procedures like management of facial wrinkles; however, it has been documented to be successful in a variety of conditions. Of particular interest to this paper are applications of BT in the maxillofacial region, concerned to dentistry. BT offers a transient, reversible, relatively safe treatment option to many conditions of interest to a dental practitioner. Dental surgeons by their virtue of being extensively aware of the anatomy of faciomaxillary region are a potential pool of operators who can use BT in their armamentarium with minor skill enhancement and thus widen the perspective of alternative, minimally invasive options to refractory conditions or invasive protocols. PMID- 27390489 TI - Radiation-induced dental caries, prevention and treatment - A systematic review. AB - Treatment of head and neck cancers (HNCs) involves radiotherapy. Patients undergoing radiotherapy for HNCs are prone to dental complications. Radiotherapy to the head and neck region causes xerostomia and salivary gland dysfunction which dramatically increases the risk of dental caries and its sequelae. Radiation therapy (RT) also affects the dental hard tissues increasing their susceptibility to demineralization following RT. Postradiation caries is a rapidly progressing and highly destructive type of dental caries. Radiation related caries and other dental hard tissue changes can appear within the first 3 months following RT. Hence, every effort should be focused on prevention to manage patients with severe caries. This can be accomplished through good preoperative dental treatment, frequent dental evaluation and treatment after RT (with the exception of extractions), and consistent home care that includes self applied fluoride. Restorative management of radiation caries can be challenging. The restorative dentist must consider the altered dental substrate and a hostile oral environment when selecting restorative materials. Radiation-induced changes in enamel and dentine may compromise bonding of adhesive materials. Consequently, glass ionomer cements have proved to be a better alternative to composite resins in irradiated patients. Counseling of patients before and after radiotherapy can be done to make them aware of the complications of radiotherapy and thus can help in preventing them. PMID- 27390490 TI - Primary malignant melanoma of oral cavity: A tertiary care center experience. AB - BACKGROUND: Primary mucosal malignant melanoma is an extremely rare, aggressive neoplasm accounting for 0.5% of all oral malignancies. Any pigmented lesion in oral cavity should have an index of suspicion, which should be investigated to detect the disease at an early stage and managed appropriately. Melanomas tend to invade locally into the tissue or metastasize more commonly than other malignant tumors of the oral cavity. MATERIALS AND METHODS: We report a retrospective case series of eight patients suffering from primary oral malignant melanoma treated in our department between 2012 and 2014. The details were recorded from the departmental computerized database and patients on follow-up. RESULTS: There were six male and two female patients with a mean age of 46.8 years. Hard palate was the most common affected site in oral cavity. Pigmented lesion?ulcer was the most common presenting symptom. Majority of patients (5 patients) were diagnosed with Stage III (distant metastasis), two patients in Stage II, and one patient in Stage I. Three patients were treated with definitive surgery and five patients with palliative chemotherapy in view of distant disease. Following surgery, two of them required adjuvant chemoradiotherapy in view of nodal spread. Patients had a mean follow-up of 10.5 months (range: 8-26 months). Patients treated with definitive surgery had a mean survival rate of 16 months (range: 10-26 months), with local recurrence in one patient. Metastatic melanoma patients treated with palliative chemotherapy had a mean disease control rate of 5 months (range 5-9 months). CONCLUSION: Oral melanoma carries dismal prognosis with a 5-year survival rate of 5-20%. Early detection of the lesion, proper evaluation, and appropriate treatment are very important to cure the disease. PMID- 27390491 TI - Camel bite: An uncommon mode of maxillofacial injury, its mechanism and fatality: Case series and review of literature. AB - INTRODUCTION: Maxillofacial injuries are presented with many different patterns. It mostly depends upon the mode of injury like physical assault, road traffic accidents, occupational injuries, fall, sport injuries and animal attacks. Animals bites are common with wild animals but attack from an otherwise calm animal like camel is unusual and unexpected. They may cause a severe kind of maxillofacial injury which ranges from minor lacerations to total loss of soft and hard tissues. Such incidences are frequently seen in Rajasthan, India where camels are kept as a pet. Present study throws light on literature related to animal bite injuries and their management along with our experience with camel bite injuries. MATERIALS AND METHODS: Twenty patients (19 male and 1 female) of different age groups with variable extent of maxillofacial trauma induced by camel attacks were included in the study. Among them, different patterns of maxillofacial injuries were observed involving both soft and hard tissue. RESULT AND CONCLUSION: This study provides the comprehensive incidence, pathophysiology, and management of camel inflicted injuries. Understanding the behavior patterns of this animal may prevent such severe injuries. PMID- 27390492 TI - Fucose: A biomarker in grading of oral cancer. AB - INTRODUCTION: Early diagnosis of cancer helps a great deal in the management of oral cancer patients. Number of proteinous markers have been employed for this purpose. Majority of them are not specific. Recently conjugated oligosaccharide with proteins and lipids have gained considerable importance in the present postgenomics and postproteomic period in the diagnostic and prognostics of cancer cases. MATERIALS AND METHODS: In this study, serum fucose levels were estimated in 50 control cases and 75 cases of oral cancer by the method of Dische and Shettles as adopted by Winzler. RESULTS: Serum fucose levels were found to be significantly higher in oral cancer cases (46.63 +/- 5.29 mg/dl) as compared to the control cases (7.22 +/- 0.26 mg/dl). The stepwise elevated serum fucose levels were found to be correlated with the histopathological grading of oral cancer. CONCLUSIONS: Estimation of such fucose conjugated proteins is suggestive to be good biomarkers in the diagnosis of oral cancer cases as well as in assessing the prognosis of such cases. PMID- 27390493 TI - Retromandibular approach in the management of condylar fractures by open reduction and internal fixation a prospective study. AB - AIM: To evaluate the efficacy and safety of the retromandibular approach in the management of condylar fractures by open reduction and internal fixation (ORIF). MATERIALS AND METHODS: A total of 20 patients with unilateral mandibular condylar fractures underwent ORIF using retromandibular approach. Pertinent data were collected and subjected to evaluation. RESULTS: The retromandibular approach was found to be expeditious in adequately exposing the fracture site and enabling ORIF. The anatomic reduction of the fractured segments and the fixation was satisfactory in all the cases. Average duration of surgery was 39 min (range: 17 56 min) for satisfactory exposure, reduction, and fixation of each condylar fracture. CONCLUSION: The retromandibular approach provides adequate exposure of the subcondylar region and should be considered as commendable alternative in the management of condylar fractures. PMID- 27390494 TI - Human papillomavirus 16 and 18 in squamous cell carcinoma of oral cavity and sexual practices: A pilot study at a Tertiary Care Hospital of North India. AB - CONTEXT: Oral squamous cell carcinoma (OSCC) is the most common malignancy in India and tobacco and betel nut chewing are well established risk factors. Despite successful campaigns to help people shun this habit in developing countries the incidence has rather gone up and HPV and sexual practices are now definitely implicated for this. AIM: An attempt was made to generate Indian data on role of HPV and sexual practices in relation to OSCC. SETTINGS AND DESIGN: A prospective observational study was conducted on 50 patients with oral squamous cell carcinoma. MATERIALS AND METHODS: Tissue biopsies from fifty patients of oral squamous cell carcinoma (OSCC) were subjected to PCR analysis to look for presence of HPV 16 and 18. Fifty patients with benign lesions were taken as control. STATISTICAL METHODS USED: The data was statistically analysed using SPSS version 22 and chi square test. RESULTS: 42% of OSCC patients were found to harbour HPV 16 and 18 whereas only 8% of patients with benign lesions had HPV 16 and 18. A significant number of HPV positive patients i.e. 9 out of 21 gave history of multiple sexual partners and oral sex. CONCLUSIONS: This high percentage of HPV in OSCC in an Indian population from a tertiary care centre in north India and its association with prevailing sexual practices is quite significant. PMID- 27390495 TI - Estimation of serum zinc, copper, and iron in the patients of oral submucous fibrosis. AB - INTRODUCTION: The role of trace elements in various diseases has been a matter of controversy with various authors reporting on conflicting data. They are receiving much attention in the detection of oral cancer and precancer as they are found to be significantly altered and have an important role in carcinogenesis. Trace elements have been extensively studied in the recent years to assess whether they have any modifying effect in the etiology of oral malignant conditions. MATERIALS AND METHODS: A study was conducted on fifty subjects with clinically diagnosed oral submucous fibrosis (OSMF) and fifty controls with no apparent lesions of the oral mucosa and without any areca nut related oral habit. RESULTS: The level of serum zinc was significantly (P < 0.0001) lower among cases (73.48 +/- 24.21) compared with controls (119.48 +/- 52.78). However, the serum copper level was significantly (P < 0.0001) higher among cases (155.50 +/- 40.13) than controls (100.40 +/- 24.52). The level of serum iron was observed to be lower among the cases (66.57 +/- 27.76) as compared to controls (94.19 +/- 35.70), and the difference was statistically significant. CONCLUSION: It can be concluded from this study that serum zinc, copper, and iron levels could be used as a potential prognostic and diagnostic markers in OSMF patients. PMID- 27390496 TI - Assessment of facial nerve injury with "House and Brackmann facial nerve grading system" in patients of temporomandibular joint ankylosis operated using deep subfascial approach. AB - BACKGROUND: Preservation of the functional integrity of the facial nerve (FN) is a critical measure of success in temporomandibular joint (TMJ) surgery. In spite of the development of a myriad of surgical approaches to the TMJ, FN remains at risk. The deep subfascial approach provides an additional layer of protection (the deep layer of the temporalis fascia and the superficial temporal fat pad) to the temporal and zygomatic branches of the FN and thus, is the safest method to avoid FN injury. OBJECTIVES: To assess FN injury following TMJ surgery using deep subfascial approach and measuring it on House and Brackman facial nerve grading system (HBFNGS). MATERIALS AND METHODS: Twenty TMJs in 18 patients were operated for TMJ ankylosis, using "the deep subfascial approach." FN function was assessed postoperatively at 24 h, 1 week, 1 month, 3 months, 6 months using HBFNGS. Statistical analysis was done using SPSS 16.0. RESULTS: Of 20 surgical sites 3 sites showed Grade III (moderate) FN injury and 17 sites showed Grade II (mild) FN injury at 24 h. The condition improved with time with full recovery of FN at all surgical sites at 6 months. CONCLUSION: The deep subfascial approach has a distinct advantage over the conventional approaches when dissecting the temporal region and is the safest method to avoid injury to FN. PMID- 27390497 TI - Implant supported overdenture in the patients with history of radio and chemotherapy for the prostate malignancy. AB - The success of dental implants in patients that have undergone chemo and radiotherapy for a region other than head and neck remain unclear, although some local and systemic factors could be contraindications to dental implant treatment. As there are very few absolute medical contraindications to dental implant treatment, but a number of conditions may increase the risk of treatment failure or complications. The case report describes the successful survival of dental implants placed in maxilla and mandible of a patient who had undergone radio and chemotherapy for prostate cancer. PMID- 27390498 TI - An indigenous method for closed reduction of pediatric mandibular parasymphysis fracture. AB - Mandibular fractures in children are very rare as compared to adults due to protected anatomic features of child and less exposure to road traffic accidents. Management becomes complicated due to inherent dynamic nature, instability of mixed dentition and fear of surgery. Conservative management can be done with the help of acrylic cap splints along with circum-mandibular wiring, intermaxillary fixation with eyelet wires, arch wires or open reduction and internal fixation with bio-resorbable plates. Different methods have various pros and cons. The choice of anesthesia is also very crucial sometimes. This case report describes a new method of closed reduction with 18 gauge needle simulated as an arch bar performed under local anaesthesia. PMID- 27390499 TI - Central cavernous hemangioma of mandible: Case report and review of literature. AB - Intraosseous hemangiomas are one of the rarest lesion of jaw bones (0.5-1%) occurring most commonly in vertebral column, skull bone, and rarely in mandible. Mainly occurs in the second decade of life with female: male predilection (2:1). Origin of hemangiomas is still debatable. World Health Organization considers it as a true benign neoplasm of vascular origin, and many authors believe it to be a hamartoma. It is very difficult to diagnose due to variable clinical and radiological features. A biopsy is not done on a routine basis due to a higher risk of hemorrhage. Management is very difficult because of massive vascular network in that region. Here, we are presenting a case report of a 14-year-old boy with intraosseous hemangioma of right body of mandible, which was treated with en bloc surgical resection of mandible and followed by reconstruction. PMID- 27390500 TI - Tuberculous osteomyelitis of mandibular condyle: A rare encounter. AB - Tuberculosis (TB), one of the oldest known microbial infectious diseases affecting humans has continued to burden our healthcare system over generations. Conventionally, primary TB usually manifests as a pulmonary infection. However, the last decade has witnessed increasing reports of extrapulmonary infections. It's often atypical clinical presentations require a high degree of clinical suspicion, especially in the developing countries with a high incidence of this infectious disease. In this report, we present one such case of tuberculous osteomyelitis of the mandibular condyle where the patient reported with the complaint of swelling on the left side of the face with no apparent systemic manifestation. PMID- 27390501 TI - Eagle's syndrome veiling as pain of odontogenic origin: Report of two cases with cone beam computed tomography illustration. AB - Eagle's syndrome, also known as an elongated styloid process, is a condition that may be the source of craniofacial and cervical pain. It is infrequently reported but is probably more common than generally considered. The symptoms related to Eagle's syndrome can be confused with those attributed to a wide variety of facial neuralgia and or oral, dental, and temporomandibular joint diseases. In this paper, there are two cases, which reported to the Department of Oral Medicine, Diagnosis, and Maxillofacial Radiology, with a chief complaint of radiating pain in the preauricular region of the face. After radiographic investigation, these cases are considered as a case of Eagle's syndrome because of increase in the size of the styloid process. PMID- 27390502 TI - Massive dedifferentiated chondrosarcoma affecting whole mandible with high recurrence potential. AB - Chondrosarcomas (CS) are slow-growing, malignant mesenchymal tumors characterized by the formation of cartilage by the tumor cells. Benign cartilage-producing tumors within the jaws are extremely uncommon, but most ultimately prove to represent low-grade CS. In the maxillofacial region, the maxilla is more commonly affected than the mandible, it comprises less than 2% of all jaw tumors. Clinically, the tumor presents as a swelling that may be painful and cause loosening of the involved teeth, with widening of the periodontal ligament space. The treatment of such lesions is wide surgical excision with regular follow up. The present report discusses the case of a 55-year-old female patient with massive multiple recurring dedifferentiated CS of mandible. PMID- 27390503 TI - Upper alveolar brown tumor as initial presentation of parathyroid adenoma. AB - Parathyroid adenoma usually presents with the signs and symptoms of hypercalcemia due to hyperparathyroidism. Brown's tumor is the late clinical consequence of untreated hyperparathyroidism and is rarely seen now-a-days due to improved screening biochemical tests. These tumors are characterized by high orthoclastic activity and bone resorption. These are usually located in the pelvis, ribs, clavicles, and extremities. This manuscript highlights a rare presentation of brown's tumor of upper alveolus in a 35-year-old female with a previously undiagnosed case of hyperparathyroidism due to a parathyroid adenoma. Blood analysis depicted high levels of serum calcium and parathyroid hormone. The patient was subjected to selective left lower parathyroidectomy and will receive follow-up to prevent further developments of the disease. Clinicians should be aware of such rare presentation of parathyroid adenomas so that unnecessary extensive surgery of brown's tumor is avoided. This case also highlights the need of detailed work up to arrive at an exact diagnosis and direct surgical intervention to the adenoma rather the secondary manifestation of the disease. PMID- 27390504 TI - Custom ocular prosthesis in rehabilitation of a child operated for retinoblastoma. AB - A maxillofacial prosthodontist forms an important link in the interdisciplinary management of a patient with anopthalmosis. Prosthetic management of an anopthalmic defect aims to deliver a well-fitting ocular prosthesis that can mimic the original eye as closely as possible, and thus restoring the patient's self-confidence and thereby rehabilitating them in the society. The fabrication of a custom ocular prosthesis is a demanding art. This case report presents a simplified technique for the fabrication of a custom ocular prosthesis for a child who had lost his eye to enucleation following retinoblastoma. Early and effective rehabilitation of the defect goes a long way in restoring the self image of a child in its early character building age. PMID- 27390505 TI - Oral eosinophilic or traumatic ulcer: A case report and brief review. AB - Eosinophilic ulcer of the oral mucosa is considered to be a benign, reactive, and self-limiting lesion, with unclear pathogenesis, manifesting as a rapidly developing solitary ulcer. We report a case of a 42-year-old man who presented with a chronic indurated ulcer of buccal mucosa adjacent to the right upper wisdom tooth. Histopathological examination showed polymorphic inflammatory infiltrate, rich in eosinophilis, involving the superficial mucosa, and the deeper muscle layer. Immunohistochemical analysis revealed single CD30+ cells scattered within an inflammatory infiltrate. The lesion was excised, and healing was uneventful with no recurrence in more than a year. PMID- 27390506 TI - Huge ossifying fibroma maxilla. AB - Maxillofacial fibro-osseous lesions comprise a group of face and jaw disorders characterized by the replacement of bone by a benign connective-tissue matrix with varying amount of mineralized substances. Fibro-osseous lesions of the maxilla are not an uncommon tumor. Majority of the lesions with fibrous and osseous components include ossifying fibroma, fibrous dysplasia, cemento ossifying fibroma, and cementifying fibroma. We present a case of 15-year-old female with huge fibroosseous lesion which was treated with total maxillectomy via a Weber-Ferguson approach. Histopathology established that fibroosseous lesion as an ossifying fibroma. PMID- 27390507 TI - An unusual occurrence of multiple epidermoid cysts in both sides of buccal mucosa: A unique and rare first case report. AB - Intraoral epidermoid cyst of buccal mucosa is generally an uncommon entity. Epidermal inclusion cyst refers sequestration of epidermal elements into the dermal and deeper tissue during the fetal period in line of fusion of embryonic process or acquired due to implantation of the epithelium due to trauma or surgery. It usually presents as slow growing asymptomatic cysts but may be symptomatic due to large size, interfering with mastication and speech or secondary infection. Surgical excision is done for removal of these cysts. We report an interesting case of multiple epidermal cysts in both sides of buccal mucosa in a 35-year-old male patient. PMID- 27390508 TI - Clicking hyoid: A rare case report and review. AB - Painful conditions of unexplained origin pose a challenging task for the clinician from both the diagnosis and treatment perspective. This might be accounted due to overlapping symptomatology; moreover, nonspecific subjective findings push the diagnostic process to a more perplexing direction. The main loophole in their management lies in difficulty to make an appropriate diagnosis. Clicking hyoid is an extremely rare anomaly of hyoid bone which produces painful clicking in throat. Here, we report a case of a young patient presented with pain and clicking in throat which aggravated on swallowing. After a series of examinations, it was diagnosed as clicking hyoid and was managed successfully by surgical treatment. The objective of this article is not only to increase awareness of the ailment so as to validate its existence but also demonstrate the significant utility of the surgical management. PMID- 27390509 TI - Immediate dental implant placement with immediate loading following extraction of natural teeth. AB - The loss of tooth in the esthetic area is often a traumatic experience for the patient. Patients may suffer real or perceived detrimental effects following the loss of one or more teeth. Dental implant offers the most cost-effective and long term solution for replacement of missing teeth with high average life expectancy, providing the patient with the best sense of security and well-being. Recently, immediate implant placement after extraction of tooth with early loading has become more common. The advantages of this procedure include fewer surgical interventions, reduction in overall treatment time, reduced soft and hard tissue loss, and psychological satisfaction to the patient. This case report describes the procedure for immediate implant placement with immediate loading of implants by provisional restorations. PMID- 27390510 TI - Who Goes Where? Exploring Factors Related to Placement Among Group Homes. AB - Despite their widespread use as a placement option for youth with mental health problems, there is relatively little research on group homes for youth. Available data highlight concerns with practices and treatment within group homes and mixed results on youth-level outcomes. However, existing research appears to collapse a wide range of group residential settings into a single amorphous category. This article explores potential variations among group homes to examine whether different programs are systematically serving different types of youth. It examines, in particular, placement in homes using the teaching family model (TFM) versus homes that do not. Findings suggest that demographics are not significantly associated with TFM placement. However, custody status, types of mental health problems, and use of psychotropic medications are. Homes appear to be serving distinct niches within a geographic area. Implications for future research and policy/practice are discussed. PMID- 27390511 TI - Differential Multiphoton Laser Scanning Microscopy. AB - Multifocal multiphoton microscopy (MMM) in the biological and medical sciences has become an important tool for obtaining high resolution images at video rates. While current implementations of MMM achieve very high frame rates, they are limited in their applicability to essentially those biological samples that exhibit little or no scattering. In this paper, we report on a method for MMM in which imaging detection is not necessary (single element point detection is implemented), and is therefore fully compatible for use in imaging through scattering media. Further, we demonstrate that this method leads to a new type of MMM wherein it is possible to simultaneously obtain multiple images and view differences in excitation parameters in a single shot. PMID- 27390513 TI - Pou4f2 knock-in Cre mouse: A multifaceted genetic tool for vision researchers. AB - PURPOSE: A transgenic mouse that expresses Cre recombinase under control of the Pou4f2-promoter (also referred to as Brn-3b and Brn-3.2) was characterized. Pou4f2 expression has been reported in a subset of retinal ganglion cells (RGCs) in the retina, in the midbrain, and in the germline. In this study, we characterize the expression pattern of this Cre-recombinase line and report its utility in targeted deletion, temporal deletion, RGC depletion, and germline targeting, which can be regulated by the sex of the Cre-carrying mouse. METHODS: Pou4f2(Cre) was mapped by using a combination of PCR and sequencing of PCR products to better understand the construct and to locate where it was inserted within the Pou4f2 locus. Cre expression patterns were examined by crossing Pou4f2(Cre/+) mice to Cre reporter mice. Immunohistochemistry was used to further define the pattern of Cre expression and Cre-mediated recombination within the retina, brain, and other tissues. RESULTS: An internal ribosome entry site (IRES) Cre cassette was inserted into the Pou4f2 gene disrupting normal gene function, as verified by the depletion of RGCs in mice homozygous for the insert. Pou4f2(Cre) expression was observed in the retina, brain, peripheral neurons, and male germ cells. Germline recombination was observed when the sire carried the Cre and the target for recombination. In all other breeding schemes, recombination was observed within subsets of cells within the retina, brain, intestines, heart, and gonads. In the retina, Cre efficiently targets recombination in neurons within the RGC layer (RGL), the inner nuclear layer (INL), and a small percentage of photoreceptors, activity that has not been previously reported. Unlike most other Cre lines active in the inner retina, recombination in Muller and other glia was not observed in mice carrying Pou4f2(Cre) . Within the visual centers of the brain, Cre targets recombination in about 15% of cells within the superchiasmatic nucleus, lateral geniculate nucleus, and superior colliculus. CONCLUSIONS: Pou4f2(Cre) provides multiple uses for the vision researcher's genetic toolkit. First, Pou4f2(Cre) is a knock-in allele that can be used to eliminate Pou4f2, resulting in depletion of RGCs. Second, expression of Cre in male germ cells makes this strain an efficient germline activator of recombination, for example, to target LoxP-flanked sequences in the whole mouse. Third, Pou4f2(Cre) efficiently targets RGCs, amacrine cells, bipolar cells, horizontal cells, and a small number of photoreceptors within the retina, as well as the visual centers in the brain. Unlike other Cre recombinase lines that target retinal neurons, no recombination was observed in Muller or other retinal glia. These properties make this Cre recombinase line a useful tool for vision researchers. PMID- 27390512 TI - Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome. AB - PURPOSE: To identify mutations in COL2A1 and COL11A1 genes and to examine the genotype-phenotype correlation in a cohort of Chinese patients with Stickler syndrome. METHODS: A total of 16 Chinese probands with Stickler syndrome were recruited, including nine with a family history of an autosomal dominant pattern and seven sporadic cases. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding and adjacent regions of the COL2A1 and COL11A1 genes. Multiplex ligation-dependent probe amplification was performed to detect the gross indels of COL2A1 and COL11A1. Bioinformatics analysis was performed to evaluate the pathogenicity of the variants. RESULTS: Five mutations in COL2A1 were identified in six of 16 probands, including three novel (c.85C>T, c.3356delG, c.3401delG) mutations and two known mutations (c.1693C>T, c.2710C>T). Of the five mutations, three were truncated mutations, and the other two were missense mutations. Putative pathogenic mutations of the COL11A1 gene were absent in this cohort of patients. Gross indels were not found in COL2A1 or COL11A1 in any of the probands. High myopia was the most frequent initial ocular phenotype of Stickler syndrome. In this study, 12 Chinese probands lacked obvious systemic phenotypes. CONCLUSIONS: In this study, three novel and two known mutations in the COL2A1 gene were identified in six of 16 Chinese patients with Stickler syndrome. This is the first study in a cohort of Chinese patients with Stickler syndrome, and the results expand the mutation spectrum of the COL2A1 gene. Analysis of the genotype phenotype correlation showed that the early onset of high myopia with vitreous abnormalities may serve as a key indicator of Stickler syndrome, while the existence of mandibular protrusion in pediatric patients may be an efficient indicator for the absence of mutations in COL2A1 and COL11A1. PMID- 27390515 TI - Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy. AB - OBJECTIVE: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. PATIENTS AND METHODS: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT) were also analyzed. RESULTS: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA) implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5) required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser peripheral iridotomy. Patient 4 had both hypotony and elevated IOP that required periodic antiglaucoma medication in the FA-implanted eye. Patient 3 did not develop steroid-response glaucoma in either eye. Optic disk examinations were obscured by fibrosis and better assessed with OCT. CONCLUSION: ADNIV patients show combined mechanism secondary glaucoma best assessed by OCT of the optic disk. The FA implants have reduced uveitic and neovascular glaucoma. Nevertheless, IOP management remains complex due to steroid response glaucoma, angle closure glaucoma, and hypotony. PMID- 27390514 TI - An ex vivo gene therapy approach in X-linked retinoschisis. AB - PURPOSE: X-linked retinoschisis (XLRS) is juvenile-onset macular degeneration caused by haploinsufficiency of the extracellular cell adhesion protein retinoschisin (RS1). RS1 mutations can lead to either a non-functional protein or the absence of protein secretion, and it has been established that extracellular deficiency of RS1 is the underlying cause of the phenotype. Therefore, we hypothesized that an ex vivo gene therapy strategy could be used to deliver sufficient extracellular RS1 to reverse the phenotype seen in XLRS. Here, we used adipose-derived, syngeneic mesenchymal stem cells (MSCs) that were genetically modified to secrete human RS1 and then delivered these cells by intravitreal injection to the retina of the Rs1h knockout mouse model of XLRS. METHODS: MSCs were electroporated with two transgene expression systems (cytomegalovirus (CMV) controlled constitutive and doxycycline-induced Tet-On controlled inducible), both driving expression of human RS1 cDNA. The stably transfected cells, using either constitutive mesenchymal stem cell (MSC) or inducible MSC cassettes, were assayed for their RS1 secretion profile. For single injection studies, 100,000 genetically modified MSCs were injected into the vitreous cavity of the Rs1h knockout mouse eye at P21, and data were recorded at 2, 4, and 8 weeks post injection. The control groups received either unmodified MSCs or vehicle injection. For the multiple injection studies, the mice received intravitreal MSC injections at P21, P60, and P90 with data collection at P120. For the single- and multiple-injection studies, the outcomes were measured with electroretinography, optokinetic tracking responses (OKT), histology, and immunohistochemistry. RESULTS: Two lines of genetically modified MSCs were established and found to secrete RS1 at a rate of 8 ng/million cells/day. Following intravitreal injection, RS1-expressing MSCs were found mainly in the inner retinal layers. Two weeks after a single injection of MSCs, the area of the schisis cavities was reduced by 65% with constitutive MSCs and by 83% with inducible MSCs, demonstrating improved inner nuclear layer architecture. This benefit was maintained up to 8 weeks post-injection and corresponded to a significant improvement in the electroretinogram (ERG) b-/a-wave ratio at 8 weeks (2.6 inducible MSCs; 1.4 untreated eyes, p<0.05). At 4 months after multiple injections, the schisis cavity areas were reduced by 78% for inducible MSCs and constitutive MSCs, more photoreceptor nuclei were present (700/um constitutive MSC; 750/um inducible MSC; 383/um untreated), and the ERG b-wave was significantly improved (threefold higher with constitutive MSCs and twofold higher with inducible MSCs) compared to the untreated control group. CONCLUSIONS: These results establish that extracellular delivery of RS1 rescues the structural and functional deficits in the Rs1h knockout mouse model and that this ex vivo gene therapy approach can inhibit progression of disease. This proof-of-principle work suggests that other inherited retinal degenerations caused by a deficiency of extracellular matrix proteins could be targeted by this strategy. PMID- 27390516 TI - A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo. AB - Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS) induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases. PMID- 27390517 TI - Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study. AB - BACKGROUND: Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25%) is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. OBJECTIVE: The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. METHODS: The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. RESULTS: Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05). New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05). However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05). CONCLUSION: ASI supplementation significantly improved bone tissue healing in rats with critical-sized defects. This study demonstrated that ASI can enhance bone repair and has potential as a therapeutic regimen in humans. PMID- 27390518 TI - Openness to and preference for attributes of biologic therapy prior to initiation among patients with rheumatoid arthritis: patient and rheumatologist perspectives and implications for decision making. AB - PURPOSE: Despite American College of Rheumatology recommendations, appropriate and timely initiation of biologic therapies does not always occur. This study examined openness to and preference for attributes of biologic therapies among patients with rheumatoid arthritis (RA), differences in patients' and rheumatologists' perceptions, and discussions around biologic therapy initiation. PATIENTS AND METHODS: A self-administered online survey was completed by 243 adult patients with RA in the US who were taking disease-modifying antirheumatic drugs (DMARDs) and had never taken, but had discussed biologic therapy with a rheumatologist. Patients were recruited from a consumer panel (n=142) and patient advocacy organization (n=101). A separate survey was completed by 103 rheumatologists who treated at least 25 patients with RA per month with biologic therapy. Descriptive and bivariate analyses were conducted separately for patients and rheumatologists. Attributes of biologic therapy included route of administration (intravenous infusion or subcutaneous injection), frequency of injections/infusions, and duration of infusion. RESULTS: Over half of patients (53.1%) were open to both intravenous infusion and subcutaneous injection, whereas rheumatologists reported 40.7% of patients would be open to both. Only 26.3% of patients strongly preferred subcutaneous injection, whereas rheumatologists reported 35.2%. Discrepancies were even more pronounced among specific patient types (eg, older vs younger patients and Medicare recipients). Among patients, 23% reported initiating discussion about biologics and 54% reported their rheumatologist initiated the discussion. A majority of rheumatologists reported discussing in detail several key aspects of biologics, whereas a minority of patients reported the same. CONCLUSION: Preferences differed among patients with RA from rheumatologists' perceptions of these preferences for biologic therapy, including greater openness to intravenous infusion among patients than assumed by rheumatologists and relative lack of discussion about key aspects of biologic therapy perceived by patients. There is a need for more open communication about treatment options, which may encourage more appropriate, timely transition to biologic therapy. PMID- 27390519 TI - Association between patients' beliefs and oral antidiabetic medication adherence in a Chinese type 2 diabetic population. AB - PURPOSE: The objective of this study was to identify, using the theory of planned behavior (TPB), patients' beliefs about taking oral antidiabetic drugs (OADs) as prescribed, and to measure the correlations between beliefs and medication adherence. PATIENTS AND METHODS: We performed a cross-sectional study of type 2 diabetic patients using structured questionnaires in a Chinese tertiary hospital. A total of 130 patients were enrolled to be interviewed about TPB variables (behavioral, normative, and control beliefs) relevant to medication adherence. Medication adherence was assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8). Spearman's rank correlation was used to assess the association between TPB and MMAS-8. Logistic regression analysis was performed to examine the relationship between different variables and MMAS-8, with statistical significance determined at P<0.05. RESULTS: From 130 eligible Chinese patients with an average age of 60.6 years and a male proportion of 50.8%, a nonsignificant relationship between behavioral, normative, and the most facilitating control beliefs and OAD adherence was found in our study. Having the OADs on hand (P=0.037) was the only facilitating control belief associated with adherence behavior. Being away from home or eating out (P=0.000), not accepting the disease (P=0.000), ignorance of life-long drug adherence (P=0.038), being busy (P=0.001), or poor memory (P=0.008) were control belief barriers found to be correlated with poor adherence. TPB is the only important determinant influencing OAD adherence among all the factors (P=0.011). CONCLUSION: The results indicate that the TPB model could be used to examine adherence to OADs. One facilitating control belief, and most of the barrier control beliefs of TPB were related to medication adherence among Chinese type 2 diabetes inpatients. It will be helpful to understand patients' self-medication and provide methods to develop instruments for identifying factors that influence OAD adherence. PMID- 27390520 TI - Mental toughness, sleep disturbances, and physical activity in patients with multiple sclerosis compared to healthy adolescents and young adults. AB - BACKGROUND: Multiple sclerosis (MS) is the most common chronic autoimmune demyelinating and inflammatory disease of the central nervous system, afflicting both the body and mind. The risk of suffering from MS is 2.5-3.5 times greater in females than in males. While there is extant research on fatigue, depression, and cognitive impairment in patients with MS during its clinical course, there is a lack of research focusing on sleep, psychological functioning, and physical activity (PA) at the point of disease onset. The aims of the present study were therefore, to assess the markers of mental toughness (MT) as a dimension of psychological functioning, sleep disturbances (SD), and PA among patients at the moment of disease onset and to compare these with the corresponding values for healthy adolescents and young adults. METHODS: A total of 23 patients with MS at disease onset (mean age =32.31 years; 91% females), 23 healthy adolescents (mean age =17.43 years; 82% females), and 25 healthy young adults (mean age =20.72 years; 80% females) took part in the study. They completed questionnaires covering sociodemographic data, MT, SD, and PA. RESULTS: Patients with MS had similar scores for MT traits as those in healthy adolescents and healthy young adults, and equivalent levels of moderate-intensity PA and SD as young adults. MS patients reported lower levels of vigorous PA compared to both healthy adolescents and young adults. CONCLUSION: The pattern of the results of the present study suggests that the onset of MS is not associated with poor MT, poor sleep, or reduced moderate-intensity PA. Lower levels of vigorous PA were observed in MS patients. Low levels of vigorous PA may lead to decreased cardiorespiratory fitness in patients with MS and, in the long run, to reduced cardiovascular health and degraded psychological functioning. PMID- 27390521 TI - Cortisol awakening response in drug-naive panic disorder. AB - BACKGROUND: It is unclear whether hypothalamic-pituitary-adrenal axis is involved in the pathophysiology of panic disorder (PD). The findings remain inconsistent. Cortisol awakening response (CAR) is a noninvasive biomarker of stress system activity. We designed the study to assess CAR in drug-naive PD patients. MATERIALS AND METHODS: We assessed CAR in 14 psychotropic drug-naive outpatients with PD and 14 healthy controls. The severity of PD was assessed with Panic and Agoraphobia Scale. The severity of anxiety and depression was screened with Hospital Anxiety and Depression Scale. RESULTS: No significant difference in CAR between PD patients and control group was found. No correlations were observed between CAR and anxiety severity measures in PD patients and controls. LIMITATIONS: The number of participating subjects was relatively small, and the study results apply to nonsuicidal drug-naive PD patients without agoraphobia and with short-illness duration. There was a lack of control on subjects' compliance with the sampling instructions. CONCLUSION: The study provides no support for elevated CAR levels in drug-naive PD patients without agoraphobia. PMID- 27390522 TI - Erratum: Parkinson's disease managing reversible neurodegeneration [Corrigendum]. AB - [This corrects the article on p. 763 in vol. 12, PMID: 27103805.]. PMID- 27390523 TI - Syncope as a presentation of acute pulmonary embolism. AB - PURPOSE: Syncope is an atypical presentation for acute pulmonary embolism (APE). There are conflicting data concerning syncope and prognosis of APE. PATIENTS AND METHODS: One hundred and seventy-nine consecutive patients aged 22-96 years (median, 68 years) with APE were retrospectively enrolled in the study. RESULTS: Prevalence of syncope was 13% (n=23) at the time of presentation. Compared to patients without syncope, those with syncope had a higher rate of central embolism (83% vs 43%, respectively, P=0.002), right ventricular dysfunction (91% vs 68%, P=0.021), and troponin positivity (80% vs 39%, P=0.001) but not 30-day mortality (13% vs 10%, P=0.716). Multivariate analysis showed that central localization (odds ratio: 9.08) and cardiac troponin positivity (odds ratio: 4.67) were the independent correlates of the presence of syncope in the patients with APE. Frequency of cardiopulmonary disease was lower, and duration from symptom onset to hospital admission was shorter in patients with syncope (P=0.138 and 0.118, respectively), although not significant. CONCLUSION: Syncope most likely represents an intermediate condition between massive APE and hypotension. In APE patients with syncope, the prognosis seems to depend on the underlying pathology, the patient's age, comorbidities and duration from symptom onset to hospital admission, and the use of thrombolytic therapy. PMID- 27390524 TI - The efficacy and safety of postoperative adjuvant transarterial embolization and radiotherapy in hepatocellular carcinoma patients with portal vein tumor thrombus. AB - OBJECTIVE: This study aims to find out the safety and efficiency of postoperative adjuvant transarterial chemoembolization (TACE) and radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). METHODS: From 2009 to 2010, a total of 92 HCC patients with PVTT were enrolled in this retrospective study. Patients were divided into three groups according to their adjuvant therapies (conservative group, n=51; TACE group, n=31; RT group, n=10). RESULTS: In our analysis, median survival in patients with postoperative adjuvant TACE (21.91+/-3.60 months) or RT (14.53+/-1.61 months) was significantly longer than patients with hepatectomy alone (8.99+/-1.03 months). But the difference between adjuvant TACE and RT was of no significance (P=0.716). Also a similar result could be observed in median disease-free survival: conservative group (6.51+/-1.44 months), TACE group (13.98+/-3.38 months), and RT group (14.03+/-2.40 months). Treatment strategies (hazard ratio [HR] =0.411, P<0.001) and PVTT type (HR =4.636, P<0.001) were the independent prognostic factors for overall survival. Similarly, the risk factors were the same when multivariate analysis was conducted in disease-free survival (treatment strategies, HR =0.423, P<0.001; PVTT type, HR =4.351, P<0.001) and recurrence (treatment strategies, HR =0.459, P=0.030; PVTT type, HR =2.908, P=0.047). Patients with PVTT type I had longer overall survival than patients with PVTT type II (median survival: 18.43+/ 2.88 months vs 11.59+/-1.45 months, P=0.035). CONCLUSION: Postoperative adjuvant TACE and RT may be a choice for HCC patients with PVTT. PMID- 27390526 TI - The clinical significance of gamma-catenin in acute myeloid leukemia. AB - Dysregulation of gamma-catenin may function as an oncogenic factor in various malignancies. We investigated gamma-catenin expression in acute myeloid leukemia (AML) and explored its role in the pathogenesis of AML. gamma-Catenin was significantly overexpressed in AML patients compared to healthy donors. The gamma catenin expression in AML patients with lower white blood cells (<30*10(9)/L) was significantly higher than those with higher white blood cells (>=30*10(9)/L). The expression levels of gamma-catenin in AML patients with mutated CEBPalpha were significantly higher than those with unmutated CEBPalpha. AML patients with lower gamma-catenin levels were more likely to achieve complete remission compared with patients who have higher gamma-catenin levels. In K562 cells, gamma-catenin knockdown suppressed cellular proliferation, while the cellular migration was greatly enhanced. Moreover, knocking down of gamma-catenin enhanced the cytotoxicity of decitabine in K562 cells. Our investigation has indicated a potential role of gamma-catenin in the pathogenesis of AML. PMID- 27390525 TI - Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis. AB - Aberrant activation of Wnt/beta-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of beta-catenin and cyclin D1 genes in Wnt/beta-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer. PMID- 27390527 TI - Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients. AB - OBJECTIVE: To investigate the relationship between serum carcinoembryonic antigen (CEA) level and epidermal growth factor receptor (EGFR) gene mutations in non small-cell lung cancer (NSCLC) patients and to analyze the influence of CEA level on postoperative survival time in lung cancer patients. METHODS: A total of 296 patients who were treated in Thoracic Surgery Department of Henan Provincial Chest Hospital from September 2011 to September 2013 were recruited. The level of tumor markers, such as CEA, was determined before the surgery, and EGFR gene mutations were detected after surgery. Thereby, the relationship between tumor makers, including CEA, and EGFR mutation and its influence on prognosis could be investigated. RESULTS: Among 296 patients, the positive rate of EGFR gene mutation was 37.84% (112/296); the mutation occurred more frequently in nonsmokers, adenocarcinoma patients, women, and patients aged <60 years (P<0.05). Both tumor markers and chemosensitivity indicators were related to the profile of EGFR mutations. Elevated squamous cell carcinoma and Cyfra21-1 as well as positively expressed ERCC1 were more common in patients with wild-type EGFR (P<0.05), whereas increased CEA level was observed more frequently in patients with EGFR gene mutation (P=0.012). The positive rate of EGFR gene mutations was higher as the serum CEA level increased, that is, the positive rate in patients with serum CEA level <5, 5-20, and >20 MUg/L was 39.81%, 45.32%, and 65.47%, respectively (P=0.004). Logistic regression analysis showed that CEA level was an independent factor in predicting EGFR gene mutations, and serum CEA level was also an independent factor in affecting the prognosis of NSCLC patients, as the overall 2-year survival rate was 73.86% in elevated CEA group and 86.43% in normal group (P<0.01). CONCLUSION: The prognosis of NSCLC patients receiving resection can be predicted according to serum CEA level, which is associated with EGFR mutations in NSCLC patients and provides a preliminarily guidance for EGFR mutations. PMID- 27390528 TI - Internal mammary sentinel lymph node biopsy: abandon or persist? AB - Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach - more systemic therapy, less loco-regional therapy - clinicians should deliberate the application of regional IMLN therapy. PMID- 27390529 TI - Association between pretreatment Glasgow prognostic score and gastric cancer survival and clinicopathological features: a meta-analysis. AB - BACKGROUND: Glasgow prognostic score (GPS) is widely known as a systemic inflammatory-based marker. The relationship between pretreatment GPS and gastric cancer (GC) survival and clinicopathological features remains controversial. The aim of the study was to conduct a meta-analysis of published studies to evaluate the association between pretreatment GPS and survival and clinicopathological features in GC patients. METHODS: We searched PubMed, Embase, MEDLINE, and BioMed databases for relevant studies. Combined analyses were used to assess the association between pretreatment GPS and overall survival, disease-free survival, and clinicopathological parameters by Stata Version 12.0. RESULTS: A total of 14 studies were included in this meta-analysis, including 5,579 GC patients. The results indicated that pretreatment high GPS (HGPS) predicted poor overall survival (hazard ratio =1.51, 95% CI: 1.37-1.66, P<0.01) and disease-free survival (hazard ratio =1.45, 95% CI: 1.26-1.68, P<0.01) in GC patients. Pretreatment HGPS was also significantly associated with advanced tumor-node metastasis stage (odds ratio [OR] =3.09, 95% CI: 2.11-4.53, P<0.01), lymph node metastasis (OR =4.60, 95% CI: 3.23-6.56, P<0.01), lymphatic invasion (OR =3.04, 95% CI: 2.00-4.62, P<0.01), and venous invasion (OR =3.56, 95% CI: 1.81-6.99, P<0.01). CONCLUSION: Our meta-analysis indicated that pretreatment HGPS could be a predicative factor of poor survival outcome and clinicopathological features for GC patients. PMID- 27390532 TI - Erratum: Reappraisal of the role of dolasetron in prevention and treatment of nausea and vomiting associated with surgery or chemotherapy [Erratum]. AB - [This corrects the article on p. 67 in vol. 4, PMID: 22427733.]. PMID- 27390531 TI - An exploratory study to evaluate Clostridium difficile polymerase chain reaction ribotypes and infection outcomes. AB - BACKGROUND: Clostridium difficile infection ranges from mild to severe prolonged diarrhea with systemic symptoms. Previous studies have assessed the correlation of some disease severity parameters to C. difficile ribotypes. However, certain clinical parameters of interest have not yet been evaluated. AIM: We conducted an exploratory study to evaluate the correlation of C. difficile ribotypes to parameters not assessed previously, notably days to diarrhea resolution (in terms of days to formed stools and days to less than three stools per day), length of hospital stay, 30-day recurrence rates, and 30-day readmission rates. Additional severity parameters evaluated include leukocytosis, serum creatinine, fever, and nausea/vomiting. METHODS: Polymerase chain reaction ribotyping was performed on C. difficile isolates from baseline stool samples of 29 patients. A retrospective chart review was conducted to assess the parameters of interest. RESULTS: The most common ribotypes were 027 (38%), 014/020 (21%), and 106/174 (21%). Numerically, 027 ribotype patients required more days to less than three stools per day versus 014/020 and 106/174 ribotype patients (P=0.2). The three ribotypes were similar regarding time to formed stools, duration of hospitalization, and 30 day readmission rate (P=0.2, 0.6, and 0.8, respectively). Recurrence within 30 days occurred in two patients with 027 and two patients with 014/020 (P=0.6). Leukocytosis and fever were more prominent with 027 than with 014/020 and 106/174 (P=0.04 for both parameters), although the degree of nausea/vomiting did not differ between the three groups (P=0.3). A serum creatinine level >=1.5 times the premorbid level was seen in only three patients, each infected with a different ribotype. CONCLUSION: Although these data provide a baseline assessment of outcomes to aid in the design of future studies, the diversity of C. difficile ribotypes within the population must be considered, and additional work with other ribotypes may further explain the association with these outcomes. PMID- 27390530 TI - Molecular docking as a popular tool in drug design, an in silico travel. AB - New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism-or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein-protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery. PMID- 27390534 TI - The contribution of maternal psychological functioning to infant length of stay in the Neonatal Intensive Care Unit. AB - OBJECTIVE: Assess maternal psychological functioning within the Neonatal Intensive Care Unit (NICU) and its contribution to neonate length of stay (LOS) in the NICU. STUDY DESIGN: Mothers of infants admitted to the NICU (n=111) were assessed regarding postpartum depression, postpartum social support, postpartum NICU stress, and maternal anxiety at 2 weeks postpartum. Illness severity was assessed with the Clinical Risk Index for Babies (CRIB). RESULTS: Postpartum depression was not significantly correlated with LOS, but was significantly correlated with trait anxiety (r=0.620), which was significantly correlated with LOS (r=0.227). Among mothers with previous mental health history, substance abuse history and CRIB score were the best predictors of LOS. For mothers without a prior mental health issues, delivery type, stress associated with infant appearance, and CRIB scores were the best predictors of LOS. In this group, LOS was found to increase on average by 7.06 days per one unit increase in stress associated with infant appearance among mothers with the same delivery type and CRIB score. CONCLUSION: Significant correlations of trait anxiety, stress associated with infant appearance, and parental role with LOS support the tenet that postpartum psychological functioning can be associated with NICU LOS. PMID- 27390533 TI - Amniotic membrane can be a valid source for wound healing. AB - Amniotic membrane (AM) can promote proper epithelialization with suppression of excessive fibrosis by creating a supportive milieu for regeneration of chronic ulcer bed. OBJECTIVE: The objective of this study is to investigate whether AM scaffold can modulate the healing of a wound by promoting tissue reconstruction rather than promoting scar tissue formation. SUBJECTS AND METHODS: AM was obtained and prepared and then applied to patients with chronic leg ulcers who were randomly divided into two different groups. Group I (control group) included eleven patients in whom ulcers were treated with conventional wound dressings that were changed daily for 8 weeks. Group II (study group) included 14 patients in whom the AM was placed in contact with the ulcer and held in place with a secondary dressing, which was changed daily. Follow-up was done to detect healing rate and detection of ulcer size, assessment of pain, and to take ulcer images (days 0, 7, 14, 21, 30, 45, and 60). RESULTS: In group I, all ulcers showed no reduction in their size, and ulcer floor remained the same. Healthy granulations were present in two ulcers (18.2%) and absent in nine ulcers (81.8%). There was no improvement of pain level in the eleven ulcers. In group II, complete healing of 14 ulcers occurred in 14-60 days with a mean of 33.3+/-14.7; healing rate range was 0.064-2.22 and the mean 0.896+/-0.646 cm(2)/day. Healthy granulations were present in 13 ulcers (92.9%) and absent in one ulcer (7.1%). Three ulcers (21.4%) were of mild severity (grade 1 ulcers) while eleven ulcers (78.6%) were of moderate severity (grade 2 ulcers). The healing rate was faster in ulcers of mild severity (1.7+/-0.438 cm(2)/day) in comparison to ulcers of moderate severity (0.673+/-0.498 cm(2)/day). Eleven cases (78.6%) showed improvement in their pain level on a scale from 0 to 10. CONCLUSION: AM graft can be of value in wound healing. Further studies are needed to confirm these findings. PMID- 27390535 TI - Digital necrosis with squamous cell carcinoma of the tonsil. AB - BACKGROUND: Digital necrosis is a rare phenomenon of paraneoplastic syndrome associated with squamous cell carcinoma of the tonsil. Since 1965, more than 70 cases have been reported worldwide in the literature. CASE REPORT: A 54-year-old male smoker presented with Raynaud's phenomenon, proceeding to frank gangrene of the fingers. Working up the case finally pointed toward carcinoma of the tonsil as the underlying cause - a rare paraneoplastic manifestation. CONCLUSION: No definite etiology has been found to be the cause of Raynaud's phenomenon in this case of the squamous cell carcinoma of the tonsil. A brief discussion of the literature is also presented. PMID- 27390536 TI - Epilepsy: addressing the transition from pediatric to adult care. AB - Adolescence is a period of rapid change, both physical and psychosocial for any young person. It can be challenging when they have ongoing health problems and when their care needs to be transitioned to the adult health care system. Transition should be a planned process of addressing the medical and associated comorbid conditions from pediatric to adult care in a coordinated manner. In most cases, the young person and their family are well known to the pediatrics services and have built a relationship based on trust and often friendship over many years. Understandably, there is significant apprehension about moving from this familiar setting to the unknown adult services. Apart from having a sound knowledge of specific childhood epileptic conditions and associated comorbid disorders, it is important that both the pediatric and adult epilepsy teams are motivated to provide a successful and safe transition for these patients. It is essential that transition is seen as a continual process and not as a single event, and good preparation is the key to its success. It is also important that general practitioners are closely engaged to ensure successful transition. An overview of how to effectively address transition in epilepsy, different models of transition, transition of relevant epilepsies, and their management is discussed. PMID- 27390537 TI - Hemodynamic Measurement Using Four-Dimensional Phase-Contrast MRI: Quantification of Hemodynamic Parameters and Clinical Applications. AB - Recent improvements have been made to the use of time-resolved, three-dimensional phase-contrast (PC) magnetic resonance imaging (MRI), which is also named four dimensional (4D) PC-MRI or 4D flow MRI, in the investigation of spatial and temporal variations in hemodynamic features in cardiovascular blood flow. The present article reviews the principle and analytical procedures of 4D PC-MRI. Various fluid dynamic biomarkers for possible clinical usage are also described, including wall shear stress, turbulent kinetic energy, and relative pressure. Lastly, this article provides an overview of the clinical applications of 4D PC MRI in various cardiovascular regions. PMID- 27390538 TI - Morphological and Functional Evaluation of Quadricuspid Aortic Valves Using Cardiac Computed Tomography. AB - OBJECTIVE: The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). MATERIALS AND METHODS: We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. RESULTS: All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). CONCLUSION: Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV. PMID- 27390539 TI - Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review. AB - Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere(r) and SIR-Spheres(r). Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma. PMID- 27390540 TI - Performance of Screening Mammography: A Report of the Alliance for Breast Cancer Screening in Korea. AB - OBJECTIVE: To analyze the diagnostic accuracy and trend in screening mammography in Korea. MATERIALS AND METHODS: We retrospectively linked the information from hospitals participating in the Alliance of Breast Cancer Screening in Korea (ABCS K) and the database of the National Cancer Screening Program. We calculated performance indicators, including the recall rate, cancer detection rate (CDR), positive predictive value (PPV), sensitivity, specificity, false-positive rate (FPR), and interval cancer rate (ICR). Changes in the performance indicators were calculated as the annual percent change with 95% confidence interval (CI). RESULTS: We enrolled 128756 cases from 10 hospitals from 2005 to 2010. The recall rate was 19.1% with a downward trend over time (-12.1% per year; 95% CI, -15.9 to -8.2). The CDR was 2.69 per 1000 examinations, without a significant trend. The PPV was 1.4% with an upward trend (20.8% per year; 95% CI, 15.2 to 26.7). The sensitivity was 86.5% without a significant trend, whereas the specificity was 81.1% with an upward trend (3.3% per year; 95% CI, 2.1 to 4.5). The FPR was 18.9% with a downward trend (-12.4% per year; 95% CI, -16.2 to -8.4). The ICR was 0.5 per 1000 negative examinations without a significant trend. There were institutional variations in the diagnostic accuracy and trend except for the CDR, sensitivity, and ICR. CONCLUSION: The sensitivity and CDR of screening mammography in the ABCS-K from 2005 to 2010 were compatible with those for Western women. The recall rate, PPV and specificity, however, were suboptimal, although they showed significant improvements over this period. A further analysis is required to explain institutional variations. PMID- 27390541 TI - Ultrasound-Guided Delivery of siRNA and a Chemotherapeutic Drug by Using Microbubble Complexes: In Vitro and In Vivo Evaluations in a Prostate Cancer Model. AB - OBJECTIVE: To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. MATERIALS AND METHODS: Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. RESULTS: Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 +/- 2.9%), which was further potentiated by application of ultrasound (55.0 +/- 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 +/- 4.90% to 36.7 +/- 1.34%, p = 0.027). CONCLUSION: Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo. PMID- 27390542 TI - Comparison of Multidetector CT and Gadobutrol-Enhanced MR Imaging for Evaluation of Small, Solid Pancreatic Lesions. AB - OBJECTIVE: To compare multidetector computed tomography (MDCT) and MRI for lesion conspicuity, as well as the detection and characterization of small solid pancreatic lesions (SPLs). MATERIALS AND METHODS: 193 patients with small SPLs (< 3 cm) and 52 patients with normal pancreas who underwent both multiphasic MDCT and gadobutrol-enhanced MRI were included in our study. Two radiologists blinded to the pathologic diagnoses independently reviewed those images, and determined the detection of "SPL per se" and "SPL in consideration of secondary features", the lesion conspicuity, the probability of pancreatic ductal adenocarcinoma (PDAC), and the most likely specific diagnosis. RESULTS: The sensitivity of MRI for "detection of SPL per se" was significantly higher than that of CT in both reviewers: 92.7% (179/193) and 97.9% (189/193), respectively, for reviewer 1 (p = 0.031) and 90.7% (175/193) and 99.5% (192/193), respectively, for reviewer 2 (p < 0.001). In addition, MRI provided better lesion conspicuity than MDCT for both reviewers (p < 0.001). However, CT and MRI did not show significant difference in sensitivity for "detection of SPL in consideration of secondary features", specificity for SPL detection, and differentiation of PDAC vs. non-PDAC (p > 0.05). The accuracies of CT and MRI for making a specific diagnosis were as follows: 85.7% (210/245) vs. 86.9% (213/245), respectively, for reviewer 1 (p = 0.736), and 91.8% (225/245) vs. 93.5% (229/245), respectively, for reviewer 2 (p = 0.454). CONCLUSION: MRI showed better lesion conspicuity than MDCT, but did not show significantly different diagnostic performance compared with MDCT for detecting and characterizing small SPLs. PMID- 27390544 TI - Diffusion-Weighted MRI of Malignant versus Benign Portal Vein Thrombosis. AB - OBJECTIVE: To validate the diffusion-weighted MRI (DWI) for differentiation of benign from malignant portal vein thrombosis. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study and waived informed consent. A total of 59 consecutive patients (52 men and 7 women, aged 40-85 years) with grossly defined portal vein thrombus (PVT) on hepatic MRI were retrospectively analyzed. Among them, liver cirrhosis was found in 45 patients, and hepatocellular carcinoma in 47 patients. DWI was performed using b values of 50 and 800 sec/mm(2) at 1.5-T unit. A thrombus was considered malignant if it enhanced on dynamic CT or MRI; otherwise, it was considered bland. There were 18 bland thrombi and 49 malignant thrombi in 59 patients, including 8 patients with simultaneous benign and malignant PVT. Mean apparent diffusion coefficients (ADCs) of benign and malignant PVTs were compared by using Mann-Whitney U test. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The mean ADC +/- standard deviation of bland and malignant PVT were 1.00 +/- 0.39 * 10(-3) mm(2)/sec and 0.92 +/- 0.25 * 10(-3) mm(2)/sec, respectively; without significant difference (p = 0.799). The area under ROC curve for ADC was 0.520. An ADC value of > 1.35 * 10(-3) mm(2)/sec predicted bland PVT with a specificity of 94.6% (95% confidence interval [CI]: 84.9-98.9%) and a sensitivity of 22.2% (95% CI: 6.4-47.6%), respectively. CONCLUSION: Due to the wide range and considerable overlap of the ADCs, DWI cannot differentiate the benign from malignant thrombi efficiently. PMID- 27390545 TI - CT Findings of Foreign Body Reaction to a Retained Endoloop Ligature Plastic Tube Mimicking Acute Appendicitis: A Case Report. AB - Many hospitals experience one or more retained surgical instrument events with risk of patient morbidity and medicolegal problems. Identification of retained surgical instrument is important. The radiologists should be familiar with imaging finding of retained surgical instrument. In a 62-year-old female with a retained plastic tube, localized peritoneal infiltration around air-containing tubular structure mimicked acute appendicitis on abdomen computed tomography (CT), one year after laparoscopic cholecystectomy. We reported CT findings of foreign body reaction related to retained Endoloop ligature plastic tube mimicking acute appendicitis. PMID- 27390543 TI - Triple Arterial Phase MR Imaging with Gadoxetic Acid Using a Combination of Contrast Enhanced Time Robust Angiography, Keyhole, and Viewsharing Techniques and Two-Dimensional Parallel Imaging in Comparison with Conventional Single Arterial Phase. AB - OBJECTIVE: To determine whether triple arterial phase acquisition via a combination of Contrast Enhanced Time Robust Angiography, keyhole, temporal viewsharing and parallel imaging can improve arterial phase acquisition with higher spatial resolution than single arterial phase gadoxetic-acid enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Informed consent was waived for this retrospective study by our Institutional Review Board. In 752 consecutive patients who underwent gadoxetic acid-enhanced liver MRI, either single (n = 587) or triple (n = 165) arterial phases was obtained in a single breath-hold under MR fluoroscopy guidance. Arterial phase timing was assessed, and the degree of motion was rated on a four-point scale. The percentage of patients achieving the late arterial phase without significant motion was compared between the two methods using the chi(2) test. RESULTS: The late arterial phase was captured at least once in 96.4% (159/165) of the triple arterial phase group and in 84.2% (494/587) of the single arterial phase group (p < 0.001). Significant motion artifacts (score <= 2) were observed in 13.3% (22/165), 1.2% (2/165), 4.8% (8/165) on 1st, 2nd, and 3rd scans of triple arterial phase acquisitions and 6.0% (35/587) of single phase acquisitions. Thus, the late arterial phase without significant motion artifacts was captured in 96.4% (159/165) of the triple arterial phase group and in 79.9% (469/587) of the single arterial phase group (p < 0.001). CONCLUSION: Triple arterial phase imaging may reliably provide adequate arterial phase imaging for gadoxetic acid enhanced liver MRI. PMID- 27390546 TI - Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea. AB - OBJECTIVE: To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). MATERIALS AND METHODS: The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. RESULTS: Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. CONCLUSION: Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD. PMID- 27390547 TI - A Case of Anomalous Origin and Course of Vertebral Artery in a Patient with Klippel Feil Syndrome. AB - Patients with Klippel-Feil syndrome (KFS) have an increased incidence of vascular anomalies as well as vertebral artery (VA) anomalies. In this article, we presented imaging findings of a 15-year-old female patient with KFS with a rare association of extraforaminal cranially ascending right VA that originated from the ipsilateral carotid bulb. Trifurcation of the carotid bulb with VA is a very unusual variation and to the best of our knowledge, right-sided one has not been reported in the literature. PMID- 27390549 TI - Listening-touch, Affect and the Crafting of Medical Bodies through Percussion. AB - The growing abundance of medical technologies has led to laments over doctors' sensory de-skilling, technologies viewed as replacing diagnosis based on sensory acumen. The technique of percussion has become emblematic of the kinds of skills considered lost. While disappearing from wards, percussion is still taught in medical schools. By ethnographically following how percussion is taught to and learned by students, this article considers the kinds of bodies configured through this multisensory practice. I suggest that three kinds of bodies arise: skilled bodies; affected bodies; and resonating bodies. As these bodies are crafted, I argue that boundaries between bodies of novices and bodies they learn from blur. Attending to an overlooked dimension of bodily configurations in medicine, self-perception, I show that learning percussion functions not only to perpetuate diagnostic craft skills but also as a way of knowing of, and through, the resource always at hand; one's own living breathing body. PMID- 27390548 TI - Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report. AB - Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation. PMID- 27390550 TI - Mixed methods evaluation of a primary eye care training programme for primary health workers in Morogoro Tanzania. AB - BACKGROUND: There are 285 million people with visual impairment (VI) worldwide including 39 million who are blind; 15 % of those with VI live in Africa, and around 80 % of VI is preventable or treatable with the right equipment, information and skills. The scarcity of human resources for eye health, particularly in Sub-Saharan Africa, is a key challenge towards achieving this goal. Therefore training primary health workers (PHW) in providing eye-care services has been seen by some authors as a way to improve access to eye-care services in remote communities. However, the package of interventions which could be effectively delivered for eye-care at the primary-care level or the set of skills and competencies that PHWs need has not yet been delineated. The aim of the study was to evaluate the effectiveness of a four day training programme of PHWs in primary eye-care conducted in Morogoro, Tanzania in 2010/2011. METHODS: A mixed methods study using pre- and immediate post-training knowledge assessment of 60 trainees, and in-depth face to face interviews with 20 PHWs and 8 service managers 2 to 3 years after the training. RESULTS: Pre-and immediate post training assessments indicated improvement in health worker knowledge about eye care in the short term. Qualitative investigations 2 to 3 years after the training showed that although staff could make the correct management decisions when presented with eye-health problems, they often could not make a correct diagnosis. PHWs and managers reported satisfaction with the content of the training but some of the less well qualified staff found it overwhelming. Theoretical teaching was appreciated by most participants but almost all suggested increasing the time spent on acquiring skills. The training manual was accepted by many and some improvements were recommended. All interviewed PHWs were keen to improve their skills and knowledge. Acquired skills and knowledge were used for identification, referral of patients and for eye-health promotion. CONCLUSION: The training program in Morogoro was considered by PHWs as broadly successful and satisfying in terms of content, methods and duration of training. However, any future programme needs to be considered within the context of strengthening wider health systems. PMID- 27390551 TI - Expression and diagnostic value of CCT3 and IQGAP3 in hepatocellular carcinoma. AB - BACKGROUND: To evaluate plasma chaperonin containing TCP1 complex subunit 3 (CCT3) and IQ-motif-containing GTPase-activating protein-3 (IQGAP3) as biomarker for hepatocellular carcinoma (HCC) screening and diagnosis. METHODS: Blood samples were collected from 126 HCC patients with HCC, 88 patients with cirrhosis and 50 healthy volunteers to detect plasma alpha-fetoprotein (AFP), CCT3 and IQGAP3 levels. Plasma AFP, CCT3 and IQGAP3 protein levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: In the plasma of HCC patients, both CCT3 and IQGAP3 were significantly higher than in patients with cirrhosis and in healthy controls (P < 0.01). CCT3 and IQGAP3 protein level correlated well with HCC etiology, tumor size, TNM stage, and child-pugh classification. CCT3 protein had higher sensitivity in the diagnosis of HCC when compared with AFP (87.3 vs 69.8 %). In addition, CCT3 and IQGAP3 protein were able to complement AFP in detecting AFP-negative HCC patients with sensitivity and specificity of 92.1 and 70.5 % and 81.6 and 71.6 %, respectively. In the small HCC group, CCT3 and IQGAP3 protein had sensitivity of 76.6 and 74.5 %, respectively. The combination of AFP + CCT3 + IQGAP3 (0.954) had significantly superior discriminative ability than AFP alone (0.815; P < 0.01). CONCLUSIONS: CCT3 and IQGAP3 are novel complementary biomarkers for HCC screening and diagnosis, especially for AFP-negative and small HCC patients. PMID- 27390552 TI - Do Affordable Housing Projects Harm Suburban Communities? Crime, Property Values, and Taxes in Mount Laurel, NJ. AB - This paper offers a mixed-method analysis of the municipal-level consequences of an affordable housing development built in suburban New Jersey. Opponents of affordable housing development often suggest that creating affordable housing will harm surrounding communities. Feared consequences include increases in crime, declining property values, and rising taxes. To evaluate these claims, the paper uses the case of Mt. Laurel, NJ - the site of a landmark affordable housing legal case and subsequent affordable housing development. Employing a multiple time series group control design, we compare crime rates, property values, and property taxes in Mt. Laurel to outcomes in similar nearby municipalities that do not contain comparable affordable housing developments. We find that the opening of the affordable housing development was not associated with trends in crime, property values, or taxes, and discuss management practices and design features that may have mitigated potential negative externalities. PMID- 27390553 TI - Nonoperative Management of Acute Upper Limb Ischemia. AB - BACKGROUND: Acute upper limb ischemia (AULI) is an uncommon emergency warranting immediate evaluation and treatment. The role of nonsurgical therapies including endovascular techniques, thrombolytics, and anticoagulation remains undefined. The authors systematically reviewed the current literature on the nonsurgical treatment of acute ischemia of the upper extremity. METHODS: A PubMed and Embase search was conducted, and articles were screened using predetermined criteria. Data collected included patient demographics, cause of upper limb ischemia, type of nonsurgical treatment used, treatment outcomes, and complications. Patients were divided into 4 treatment groups: catheter embolectomy, catheter-directed thrombolysis, endovascular stenting, and anticoagulation/medical therapy alone. RESULTS: Twenty-three retrospective studies met the search criteria. Of 1326 reported occlusions, 92% (1221) were attributed to thromboembolic disease. The second most common cause was iatrogenic (1.5%). Overall limb salvage rates were excellent with catheter embolectomy (862 of 882 cases, 97.7%) and catheter directed thrombolysis (110 of 114 cases, 96.5%). Limb salvage rates were also high with anticoagulation/medical therapy (158 of 165 cases, 95.8%), but poor functional outcomes were more often reported. CONCLUSIONS: High-quality evidence to guide the nonsurgical treatment of AULI is lacking. Retrospective studies support the utility of catheter-based embolectomy and thrombolysis for distal ischemia. Whether a surgical or nonsurgical approach is taken, anticoagulation therapy remains a mainstay of both treatment and prevention of AULI. Because AULI patients often have underlying cardiac and/or systemic disease, a multidisciplinary approach is essential to minimize complications and prevent future occurrences. PMID- 27390554 TI - A Multicenter, Prospective, Randomized, Pilot Study of Outcomes for Digital Nerve Repair in the Hand Using Hollow Conduit Compared With Processed Allograft Nerve. AB - BACKGROUND: Current repair options for peripheral nerve injuries where tension free gap closure is not possible include allograft, processed nerve allograft, and hollow tube conduit. Here we report on the outcomes from a multicenter prospective, randomized, patient- and evaluator-blinded, pilot study comparing processed nerve allograft and hollow conduit for digital nerve reconstructions in the hand. METHODS: Across 4 centers, consented participants meeting inclusion criteria while not meeting exclusion criteria were randomized intraoperatively to either processed nerve allograft or hollow conduit. Standard sensory and safety assessments were conducted at baseline, 1, 3, 6, 9, and 12 months after reconstruction. The primary outcome was static 2-point discrimination (s2PD) testing. Participants and assessors were blinded to treatment. The contralateral digit served as the control. RESULTS: We randomized 23 participants with 31 digital nerve injuries. Sixteen participants with 20 repairs had at least 6 months of follow-up while 12-month follow-up was available for 15 repairs. There were no significant differences in participant and baseline characteristics between treatment groups. The predominant nerve injury was laceration/sharp transection. The mean +/- SD length of the nerve gap prior to repair was 12 +/- 4 mm (5-20 mm) for both groups. The average s2PD for processed allograft was 5 +/- 1 mm (n = 6) compared with 8 +/- 5 mm (n = 9) for hollow conduits. The average moving 2PD for processed allograft was 5 +/- 1 mm compared with 7 +/- 5 mm for hollow conduits. All injuries randomized to processed nerve allograft returned some degree of s2PD as compared with 75% of the repairs in the conduit group. Two hollow conduits and one allograft were lost due to infection during the study. CONCLUSIONS: In this pilot study, patients whose digital nerve reconstructions were performed with processed nerve allografts had significantly improved and more consistent functional sensory outcomes compared with hollow conduits. PMID- 27390555 TI - Proximal Interphalangeal Joint Extension Block Splint. AB - BACKGROUND: Extension block splinting of the proximal interphalangeal (PIP) joint is a simple and useful treatment option although the practical application of this technique has remained undefined in the literature. METHODS: This article provides a step-by-step technique for the construction of a reliable PIP extension block splint and also reviews basic indications for treatment with a PIP extension block splint as well as other PIP extension block splint designs. RESULTS: The proposed splint design outlined in this article is reliable, easy to reproduce and easy for patients to manage when treated with a PIP extension block splint. CONCLUSIONS: PIP extension block splinting has a role for certain injuries and certain post-operative protocols. A reliable splint design that is easy to manage makes this treatment choice more attractive to the surgeon and the patient. PMID- 27390556 TI - Correlations of Median Nerve Area, Strain, and Nerve Conduction in Carpal Tunnel Syndrome Patients. AB - BACKGROUND: The objective of this study was to see if ultrasound-interpreted median nerve strain and cross-sectional area correlate with abnormal nerve conduction studies and thumb opposition strength in patients with carpal tunnel syndrome (CTS). METHODS: Sixty wrists of 30 idiopathic CTS patients were assessed by ultrasound and nerve conduction study. Distal motor latency, cross-sectional area, and strain ratio of the median nerve were measured. In addition, thumb opposition strength was classified using the manual muscle testing grade from 0 to 5, clinically. The strain ratio was defined as the strain of the reference coupler divided by the strain of the median nerve. The correlations between clinical examinations of distal motor latency, cross-sectional area, strain ratio, and thumb opposition strength were estimated with the Spearman rank correlation coefficients. RESULTS: The correlation coefficients between distal motor latency and strain ratio, distal motor latency and cross-sectional area, and strain ratio and cross-sectional area were .597, .352, and .324, respectively. The correlation coefficients between thumb opposition strength and distal motor latency, thumb opposition and cross-sectional area, and thumb opposition and strain ratio were -.523, -.307, and -.358, respectively. All of the correlations showed statistical significance. The correlation coefficients between distal motor latency and strain ratio, and thumb opposition and distal motor latency, were relatively high. CONCLUSIONS: The results of this study suggest that the nerve conduction delay is related to changes in the material properties of the median nerve. In addition, nerve conduction study was the principal indicator of the thumb opposition strength. PMID- 27390557 TI - Translation and Cross-Cultural Adaptation of the 6-Item Carpal Tunnel Syndrome Symptoms Scale and Palmar Pain Scale Questionnaire Into Brazilian Portuguese. AB - BACKGROUND: There are several medical questionnaires to evaluate the quality of life of carpal tunnel syndrome patients. However, most measures are only available in English. We chose to translate and culturally adapt to Portuguese the Six-Item Carpal Tunnel Syndrome Symptoms Scale and Palmar Pain Scale (CTS-6) questionnaire because it provides objective assessment using a small number of questions. METHODS: The translation and cultural adaptation were carried out according to the medical literature and consisted of five steps: (1) initial translation by two translators fluent in both languages, (2) association of initial translations, (3) back translation to Portuguese by two native speakers of English, (4) association of back translation and (5) comparison with the original version. RESULTS: The Portuguese version was administered to patients with carpal tunnel syndrome and difficulties were noted concerning the comprehension and completion of the translated questionnaire. Patients had difficulty in understanding the horizontal layout of the response choices. Without altering the content, we changed the response choices to a vertical layout and re-administered the questionnaire to a new sample of patients followed up in the same ambulatory care service. We noted a substantial improvement in comprehension and completion of the questionnaire after the modifications. CONCLUSIONS: Availability of a Portuguese version of the Six-Item Carpal Tunnel Syndrome Symptoms Scale and Palmar Pain Scale (CTS-6) questionnaire will allow an objective evaluation of the treatment of a syndrome that is very prominent in medical practice. PMID- 27390558 TI - Evaluation of Cold Sensitivity, Pain, and Quality of Life After Upper Extremity Nerve Injury. AB - BACKGROUND: The purpose of this study was to evaluate the relationship between reported cold sensitivity, pain, and impact on quality of life (QoL) after upper extremity nerve injury. METHODS: This cross-sectional study included adults more than 6 months after an upper extremity nerve injury. Assessment included the Pain Evaluation Questionnaire (pain descriptors, questionnaire, pain intensity, impact on QoL), and Cold Intolerance Severity Scale (CISS). Statistical analyses evaluated the relationships between the Pain Evaluation Questionnaire, CISS, and independent variables. RESULTS: There were 70 patients (mean age 42 +/- 16 years). There were high levels of pain, cold sensitivity, and impact on QoL reported. Patients selecting the adjective "coldness" had significantly higher CISS scores (P = .005), pain intensity (P= .008), and impact on QoL (P < .006). Impact on QoL and CISS (r = .35) were moderately correlated. There were significant correlations (P < .01) between the level of cold-induced pain and CISS (r = .78), overall pain intensity (r = .58), pain descriptor score (r = .49), and impact on QoL (r = .32). CONCLUSIONS: Cold-induced pain is associated with higher cold sensitivity scores and greater impact on QoL. Reporting a single descriptor "coldness" and ranking cold-induced symptoms were strongly associated with higher cold sensitivity scores and impact on health-related QoL. This may have important implications for quick screening to identify patients with cold sensitivity, and future studies in larger patient samples are necessary to provide additional evidence. PMID- 27390559 TI - Wide Awake Trigger Finger Release Surgery: Prospective Comparison of Lidocaine, Marcaine, and Exparel. AB - BACKGROUND: Local anesthetics are routinely used in hand surgery for procedures such as trigger finger releases (TFRs). However, little is known as to the difference in efficacy and patient experience with various local anesthetics. We prospectively evaluated the efficacy of Lidocaine (L), Marcaine (M), and Exparel (E) to elucidate differences in pain scores and opioid consumption between these groups. METHODS: All consecutive TFR performed over a 6-month period in 2014 at our institution were divided to receive Lidocaine, Marcaine, or Marcaine with postoperative Exparel. Pain levels, daily opioid consumption, and adverse reactions were recorded and analyzed for postoperative day (POD) 0-3. RESULTS: A total of 154 patients were enrolled (L:53, M:50, E:51). The Lidocaine group reported the highest pain levels for POD 0-1. Marcaine pain levels were similar to Exparel on POD 0 but higher on POD 1. Opioid consumption on POD 0-1 was significantly different with E:27%, M:58% and L:59% as was the number of pills consumed (E:0.70, M: 1.08 and L:1.62). In addition, 50% of Exparel patients required no pain medications and experienced significantly less adverse reactions (E:4%, M:10%, L:13%). By POD 2-3, there were no statistical differences between the 3 groups. CONCLUSIONS: Patients treated with Marcaine attain better pain control than Lidocaine on POD 0-1but only patients who received Exparel maintained the lowest pain levels through POD 0-3 while using little-to-no opioid medications and with less adverse reactions than Lidocaine or Marcaine alone. PMID- 27390561 TI - Radiation Exposure and Hand Dominance Using Mini C-Arm Fluoroscopy in Hand Surgery. AB - BACKGROUND: The mini C-arm is popular with hand surgeons, and they are particularly at risk for radiation exposure, as they cannot easily distance themselves from the radiation beam. We hypothesized that the nondominant hand receives more radiation exposure than the dominant hand as it is generally closer to the radiation source. This study seeks to determine whether a hand surgeon receives a different amount of radiation exposure to their hands based on hand dominance and then accounting for this, provide a more accurate assessment of hand radiation exposure from mini C-arm fluoroscopy. METHODS: Two fellowship trained hand surgeons wore ring dosimeters on both hands during surgeries with mini C-arm fluoroscopy involving bony work of the forearm and hand. Radiation exposure to the hands was measured from ring dosimeters. RESULTS: Six-ring dosimeter pairs were worn during 64 cases, averaging 10.7 cases per ring. No ring met the minimal dose threshold of 30 mrem to record a numerical value. Each ring experienced an average of 413 seconds of fluoroscopy time and 66.3509 cGy*cm(2) of radiation output from the mini C-arm. CONCLUSIONS: The results do not allow comparison of radiation exposure related to hand dominance. Assuming worst-case scenario: each ring measured 29 mrem (just below the threshold), the surgeon's hands experienced 2.7 mrem per case. This would allow a hand surgeon to perform 18 391 cases per year before exceeding the allowable annual hand exposure limit of 50 000 mrem set by the National Council of Radiation Protection and Measurements and International Commission on Radiological Protection. PMID- 27390560 TI - Utility of Postoperative Imaging in Radial Shaft Fractures. AB - BACKGROUND: Postoperatively, radial shaft fractures are often followed clinically with serial radiographs to assess for fracture healing. Currently, there is no standard of care regarding postoperative imaging for these injuries. The purpose of this study is to determine whether imaging influences management decisions. METHODS: Patients who presented to a level I trauma center between 2009 and 2014 with an operatively treated radial shaft fracture were retrospectively screened for inclusion in our study. Patients with ipsilateral ulna or radius fractures, or with inadequate imaging or inadequate follow-up, were excluded. Four blinded, board-certified, orthopedic surgeons reviewed the postoperative films twice for each patient and stated whether the imaging would influence management decisions. Images were separated into 3 groups based on time from surgery: 0 to 4 weeks, 4 to 8 weeks, and greater than 8 weeks. The number of times imaging influenced these hypothetical management decisions was recorded. Interobserver and intraobserver agreements were calculated using Fleiss's and Cohen's kappa coefficients, respectively. RESULTS: One hundred eighteen patients underwent operative fixation for an isolated radial shaft fracture, of whom 38 met inclusion criteria. Imaging from 0 to 4 weeks, 4 to 8 weeks, and greater than 8 weeks postoperatively resulted in a change of management in 0%, 32%, and 16% of patients, respectively. After 4 weeks, changes were primarily for immobilization and activity-level modification. Intraobserver and interobserver agreement kappa coefficients were 0.761 and 0.563, respectively. CONCLUSIONS: Films obtained within 4 weeks of surgery for radial shaft fractures are unlikely to change postoperative management and may not be warranted during routine postoperative follow-up. PMID- 27390562 TI - The Epidemiology of Finger Dislocations Presenting for Emergency Care Within the United States. AB - BACKGROUND: There are little demographic data on finger dislocation injuries. This study examines the epidemiological characteristics of patients presenting for emergency care of finger dislocations within the United States. METHODS: The National Electronic Injury Surveillance System was queried for finger dislocation injuries treated in US emergency departments between 2004 and 2008. Weighted estimates, in conjunction with Census data, were used to analyze patient demographics, injury locales, and incidence rates within and between, demographic groups. RESULTS: During the 5-year study period, an estimated 166 561 finger dislocations were treated in 1 499 222 917 person-years: an incidence rate of 11.11 per 100 000 person-years. Males were predominantly affected (78.7%) at an incidence rate of 17.8 per 100 000. The rate in females was 4.65 per 100 000 person-years. Most dislocations occurred in the 15- to 19-year age group (38.6 dislocations per 100 000 person-years). Among racial groups, blacks (16.8) were affected more than whites (7.72) or patients characterized as "other" (4.90). In terms of injury venue, 35.9% of cases took place at a sporting or recreational facility. In addition, 44.7% of sports-related dislocations occurred while playing either basketball or football. CONCLUSIONS: In the United States, finger dislocations appear to occur most often in black males 15 to 19 years of age and among sports participants, particularly basketball and football players. PMID- 27390564 TI - Predicting Fracture Risk for Enchondroma of the Hand. AB - BACKGROUND: Enchondromas are benign cartilage tumors that can cause pathologic fractures involving the digits of the hand. The purpose of this study is to identify objective reproducible clinical criteria that are associated with fracture that can be used to guide clinical decision making. METHODS: A total of 54 enchondroma cases involving the hand were retrospectively reviewed. Criteria examined included age, gender, the hand involved (left vs right), bone involved, the digit involved, and longitudinal percentage of the bone occupied by the lesion on anteroposterior (AP) radiographs. RESULTS: There was a statistically significant difference between the fracture and nonfracture group in regard to age, the digit involved, bone involved, and the percentage of bone occupied by the lesion on AP radiographs. CONCLUSION: This investigation provides evidence that patient age, the affected finger, the affected bone, and the percentage of the bone occupied by the pathologic lesion on AP radiographs can be used to predict pathologic fracture risk for enchondromas. PMID- 27390563 TI - The Trapeziometacarpal Arthrosis Symptoms and Disability Questionnaire: Development and Preliminary Validation. AB - BACKGROUND: Symptoms and disability at the trapeziometacarpal (TMC) joint are typically assessed with general measures that may not be able to accurately discriminate between TMC arthrosis-specific versus other hand and arm condition concerns. The objective was to develop and preliminary validate the Trapeziometacarpal Arthrosis Symptoms and Disability (TASD) questionnaire designed to assess symptoms and disability at the TMC joint. METHODS: English speaking patients (50 years or older) were enrolled in 1 of 2 samples (sample 1, 64 patients specifically presented for treatment of TMC arthrosis; sample 2, 64 patients received an incidental diagnosis of previously undiagnosed TMC arthrosis when presenting for treatment of another, not thumb-related condition). Principal component analysis identified the number of subscales (factors) and factor loadings of all items (ie, structural construct validity). Internal consistency was assessed with Cronbach alpha. Convergent, discriminant, and known-groups construct validity of the subscales were assessed with Spearman correlations. RESULTS: The final TASD has 12 items and 2 subscales, as confirmed by principal component analysis: symptoms (7 items) and disability (5 items). The subscales' internal consistency was good to excellent in both samples. The TASD showed good convergent validity as evidenced by moderate to strong correlations between both subscales and upper extremity disability, pain intensity, depression, self efficacy, and key pinch strength (sample 1). The TASD also showed good discriminant, and good known-groups validity. CONCLUSIONS: The concise TASD is useful in assessing symptoms and disability related to TMC arthrosis, has a simple scoring system and administration mode (self-administered), and is free. PMID- 27390565 TI - Trends in the Level of Evidence in Clinical Hand Surgery Research. AB - BACKGROUND: The application of evidence-based medicine (EBM) to the practice of hand surgery has been limited. Production of high-quality research is an integral component of EBM. With considerable improvements in the quality evidence in both orthopedic and plastic and reconstructive surgery, it is imperative that hand surgery research emulates this trend. METHODS: A systematic review was performed on all hand surgery articles published in 6 journals over a 20-year period. The journals included Plastic and Reconstruction Surgery, Journal of Plastic, Reconstructive and Aesthetic Surgery, Journal of Hand Surgery-European Volume, Journal of Hand Surgery-American Volume, Journal of Bone & Joint Surgery, and the Bone & Joint Journal. The level of evidence of each article was determined using the Oxford level of evidence. The quality of methodology of randomized controlled trials (RCTs) was assessed using Jadad scale. Statistical analysis involved chi squares and Student t test (P < .05). RESULTS: A total of 972 original hand surgery research articles were reviewed. There was a significant increase in the average level of evidence of articles published between1993 and 2013. High quality evidence only accounted for 11.2% of evidence published, with a significant increase over the study period (P = 0.001). Quantitative evaluation of the 26 published RCTs, using Jadad scale, revealed a progressive improvement in study design from 0.3 in 1993 to 3.33 in 2013. CONCLUSIONS: Hand surgery research has mirrored trends seen in other surgical specialties, with a significant increase in quality of evidence over time. Yet, high-quality evidence still remains infrequent. PMID- 27390566 TI - The Effects of Early Antibiotic Administration on Bacterial Culture Growth From Hand Abscesses. AB - BACKGROUND: Traditional management of hand abscesses consists of withholding antibiotics prior to drainage to optimize bacterial culture growth and outcome. The purpose of this study was to determine the effect of preoperative empiric antibiotics on the rate of culture growth and rate of adverse events in patients with acute hand abscesses. METHODS: We performed a retrospective review of prospectively collected data on 88 consecutive hand abscesses that received empiric antibiotics prior to incision and drainage from 2012 to 2013 at an urban academic institution. We analyzed patient demographics, bacteriology, culture growth results, time to surgery, and frequency of adverse events. RESULTS: The overall rate of positive culture growth was 90% (n = 79) despite running the antibiotics for a mean of 31 hours prior to debridement. Furthermore, 96% of the isolates were given a susceptible antibiotic during that time. The mean number of debridements was 1.5 per patient, but 4 re-operations were necessary for wound complications. No patients required an amputation or were upgraded to intensive care. CONCLUSIONS: Preoperative empiric antibiotic administration does not appear to greatly reduce bacterial culture growth from hand abscesses. The adverse events are relatively few for simple abscesses treated with pre-surgical antibiotics and decompression within 24 hours. PMID- 27390567 TI - Biomechanical Analysis of Internal Fixation Methods for Distal Interphalangeal Joint Arthrodesis. AB - BACKGROUND: The biomechanical performance of distal interphalangeal joint (DIPJ) fixation techniques in response to cyclic and load-to-failure bending loads is generally unknown. The purpose of this study is to assess the performance of 4 commonly used techniques for DIP arthrodesis. METHODS: Phalanges were fixed by one of the following techniques: (1) 2 parallel Kirschner wires (K-wires), (2) 1 longitudinal K-wire and 1 oblique K-wire, (3) an Acutrak(r) 2 Micro headless compression screw, or (4) 90-90 wiring. The phalanges were loaded in cantilever bending on the palmar side of the phalange for 3000 cycles, then loaded-to failure. RESULTS: The 90-90 wiring was significantly worse than the other 3 methods in 9 of 10 parameters analyzed. Both K-wire methods and the screw produced similar results in nearly all parameters. CONCLUSIONS: Given the lack of difference in biomechanical performance between K-wires and compression screws, consideration should be given to other factors such as cost and complication profiles when choosing an implant for DIPJ fusion. PMID- 27390568 TI - Parsonage-Turner Syndrome: Clinical and Epidemiological Features From a Hand Surgeon's Perspective. AB - BACKGROUND: Parsonage-Turner Syndrome (PTS) is a rare but serious condition characterized by spontaneous paresis of the upper extremity, typically lasting several months with variable recovery. With little literature on the behavior of PTS from a hand surgeon's perspective, accurate diagnosis and subsequent counseling of patients with PTS can be challenging. METHODS: This study is a retrospective evaluation of the clinical features of all PTS patients seen over a 9-year period. Data was collected for gender, side affected, handedness, inciting event, clinical presentation, nerve involvement, time taken for recovery, and extent of recovery. RESULTS: Thirty-eight adult cases of PTS were identified, representing an incidence of 0.34 per 1000. Fifty-five percent were female, with predomination of right handedness and dominant upper extremity involvement (60% and 58%, respectively). There was an inciting incident identified in 42% of cases, and 37% of these involved surgery. Twenty-nine percent of cases presented without experiencing typical neuropathic pain. There was a predomination of anterior interosseous nerve (AIN) or posterior interosseous nerve (PIN) involvement (42% overall). Only 44% of patients achieved a complete recovery, taking a mean duration of 10 months. CONCLUSIONS: This study highlights both the rarity and atypical spectrum of clinical presentation of PTS, especially considering the more common involvement found for AIN and PIN. This highlights the likelihood that patients presenting with PTS to a hand surgical practice may differ from those typically described in the literature. The poor rate of recovery is in line with other recent reports and contrasts with the more positive outcomes found in earlier studies. PMID- 27390569 TI - Arthroscopic Trapeziectomy With Suture Button Suspensionplasty: A Retrospective Review of 153 Cases. AB - BACKGROUND: Arthroscopic trapeziectomy with suture button suspensionplasty (ATBS) is a relatively new surgical option for the treatment of thumb carpometacarpal (CMC) osteoarthritis. Although ATBS has many potential benefits over alternative surgical treatments for CMC arthritis, little data exist regarding its safety and complication rates. The purpose of this study was to demonstrate that ATBS is associated with a low risk of complications within 1 year of surgery. METHODS: A retrospective review of patients treated with ATBS by one senior hand surgeon over a span of 3 years was performed. RESULTS: A total of 153 cases of ATBS were performed in 136 patients. Ninety-seven cases involved arthroscopic hemitrapeziectomies, and 56 involved arthroscopic complete trapeziectomies. There were 44 males and 92 females with a mean age of 62. Thirty-eight percent of the cases were graded as Eaton stage IV, 46% stage III, and 14% stage II CMC arthritis, while 3 cases (2%) were performed as revisions. Mean follow-up duration was 58 weeks. Mean preoperative key pinch strength of the affected versus the unaffected side was 92% compared with 95% postoperatively. Revision surgery was performed in 9 out of 153 cases (<6%). Of those 9 cases, 5 had additional minor bony debridement with subsequent improvement in pain, 3 had the implant repositioned due to button prominence, and 1 patient presented with osteomyelitis of the first and second metacarpals that was successfully treated with button removal and an antibiotic regimen. CONCLUSIONS: ATBS is a safe, minimally invasive procedure for treatment of symptomatic stages II through IV thumb CMC arthritis. PMID- 27390570 TI - Single Incision Distal Biceps Repair With Hemi-Krackow Suture Technique: Surgical Technique and Early Outcomes. AB - BACKGROUND: Many surgical methods exist for distal biceps repair. We present the technique and early outcomes of a series of distal biceps repairs completed with a novel suturing technique utilizing a hemi-Krackow locking stitch at the tendon bone interface. METHODS: A retrospective review was performed of patients who underwent primary distal biceps repair using a single anterior incision with 2 suture anchors utilizing a hemi-Krackow stitch. With both anchors, a locking stitch along the tendon edge was complimented by the other strand passing through the central aspect of the distal tendon and advanced to pull the tendon edge down to the bone with appropriate tension. Patients with revision surgery and the use of allograft were excluded. Clinical outcomes included elbow range of motion and grip strength. All patients completed a Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire and reported satisfaction level, pain level, and any postoperative complications. RESULTS: Fourteen patients with an average age of 51.3 years (range, 27.8-66.4 years) were included in the study. The dominant arm was injured in 9 cases. At an average of 16.4 months' follow-up (range, 6.8-34.3 months), all patients had elbow range of motion of 0 degrees to >130 degrees , and grip strength was 101.5% of the uninjured arm (range, 70.6% 121.4%). The Average QuickDASH score was 6.5 (range, 0-36.5). CONCLUSION: Single incision biceps repair with suture anchor fixation using our hemi-Krackow stitch provided a strong repair allowing easy tensioning of the biceps tendon to bone and showed satisfactory functional outcomes at early follow-up. No patients required revision surgery, and there was only 1 case of transient nerve complaints. PMID- 27390571 TI - Interfascicular Renal Cell Carcinoma Metastasis to the Ulnar Nerve: A Case Report. AB - BACKGROUND: Metastatic solid tumors to the hand and peripheral nerves are exceedingly rare independent occurrences. Their occurrence together has never been reported in the literature. METHODS: We present a case report of a 69 year old male with a previous history of renal cell carcinoma (RCC) presenting with a rapidly-growing painful mass located at the right volar ulnar wrist, found to have endoneural solid tumor metastatic RCC to the ulnar nerve. RESULTS: Preoperative MRI imaging of the wrist revealed a heterogeneous mass on the volar aspect of the wrist extending along the length of the ulnar artery and nerve to the level of Guyon's canal. Pathologic examination of an incisional biopsy of the mass was consistent with metastatic renal clear cell carcinoma cells, which were infiltrating nerve and surrounding soft tissue. The patient underwent local radiation therapy to the wrist and hand with interval decrease in size of the mass and symptom improvement. CONCLUSION: Solid tumor metastasis, although exceedingly rare, must be considered in the differential diagnosis of a patient with previous cancer history presenting with a wrist or hand mass associated with peripheral neuropathy. PMID- 27390572 TI - Treatment of a Recurrent Neuroma Within Nerve Allograft With Autologous Nerve Reconstruction. AB - BACKGROUND: The purpose of this case report is to describe the findings of a neuroma within an allograft, highlight the unique opportunity to evaluate the allograft (following human engraftment) ex vivo histologically, to reinforce an effective treatment strategy, and review outcomes in peripheral nerve surgery regarding gap defect distance. METHOD: A 55-year-old, right hand dominant man suffered a workplace injury 37 years ago resulting in lacerations and crush injury of the palm and lacerations of the left index finger requiring multiple neuroma excisions and eventual ray amputation. In an attempt to address stump neuroma pain and restore sensation of the radial digital nerve of the middle finger, which was lost after the ray amputation, a neuroma was resected and reconstructed with a 45-mm bioabsorbable allograft (AxoGen, Inc, Alachua, Florida). After the inciting injury in 1977, the patient initially presented to our clinic in 2013 with return of pain at the palm and numbness along the distribution of the common digital nerve and radial nerve of the middle finger prompting surgical exploration. A recurrent common digital nerve neuroma was identified at the proximal aspect of the allograft measuring 20 mm and was resected along with the remaining allograft. RESULTS: A 50-mm reversed superficial peroneal interpositional nerve graft was used for reconstruction resulting in progressive resolution of pain. On 6-month follow-up, the patient regained indiscriminate sensation with moving 2-point discrimination at the pulp of the middle finger with improved grasp function. CONCLUSION: In the setting of recalcitrant neuromas and intractable pain following multiple neuroma excisions, allografts may be suboptimal in reconstruction of larger gap defects. Autologous reconstruction with porcine submucosa extracellular matrix, as in this case, can avoid tethering, local ischemia, and nerve traction to optimize outcomes. PMID- 27390573 TI - Photovoice as a Method for Revealing Community Perceptions of the Built and Social Environment. AB - Over the last number of years there has been growing interest in the use of community-based participatory research (CBPR) for preventing and controlling complex public health problems. Photovoice is one of several qualitative methods utilized in CBPR, as it is a participatory method that has community participants use photography, and stories about their photographs, to identify and represent issues of importance to them. Over the past several years photovoice methodology has been frequently used to explore community health and social issues. One emerging opportunity for the utilization of photovoice methodology is research on community built and social environments, particularly when looking at the context of the neighbourhood. What is missing from the current body of photovoice literature is a critique of the strengths and weaknesses of photovoice as a method for health promotion research (which traditionally emphasizes capacity building, community-based approaches) and as a method for revealing residents' perceptions of community as a source of health opportunities or barriers. This paper will begin to address this gap by discussing the successes and challenges of using the photovoice methodology in a recent CBPR project to explore community perceptions of the built and social environment (with the ultimate goal of informing community-based chronic disease prevention initiatives). The paper concludes with methodological recommendations and directions for future research. PMID- 27390574 TI - Author's response to: "Harmful effects form one puff of shisha-pen vapor: methodological and interpretational problems in the risk assessment analysis". PMID- 27390575 TI - Harmful effects from one puff of shisha-pen vapor: methodological and interpretational problems in the risk assessment analysis. AB - With this letter we express our concerns about the applicability of the proposed Margin of Exposure analysis as a method of risk assessment for propylene glycol and glycerol exposure from a shisha-pen type electronic cigarette. The studies used to determine the Margin of Exposure were evaluating the effects in humans or animals of continuous exposure to these chemicals in every single breath, whereas electronic cigarettes are used intermittently by consumers, resulting in lower and discontinuous exposure. Moreover, the authors make no clear distinction between irritation and harm, neither do they discuss the effects of exposure compared to continuous smoking. PMID- 27390576 TI - Spinal Anesthesia Facilitates the Early Recognition of TUR Syndrome. AB - OBJECTIVES: To investigate what clinical features typically present in transurethral resection (TUR) syndrome and to see which classically present first. The purpose of the study was to establish whether or not a particular method of anesthesia is preferred in detecting this syndrome in its early stages. METHODS: A total of 1,502 transurethral resection of the prostate (TURP) over a 15 year period were reviewed to see which, if any, went on to experience this complication. Of these cases, 48 developed TUR syndrome. The case records were reviewed retrospectively and the presenting clinical features were analysed. All TURPs were routinely performed under spinal anesthesia and followed a standardised set up. The irrigation fluid used in all operations was Glycine 1.5%. RESULTS: Forty eight patients displayed clinical features of TUR syndrome giving an incidence of 3.2%. Trainees of varying experience caused all but one case. Median resection time, resection weight and volume of intraoperative glycine irrigation fluid were 55 minutes (range 40-75 minutes), 44 grams (range 24-65 g), and 28 l (24-48 l) respectively. Only 16/48 TURPs had a recorded capsular perforation. Pre- vs. post-operative median hematocrit, hemoglobin and serum sodium were 0.42 vs. 0.33, 14.2 g/dl vs. 10.1 g/dl and 142 mmol/l vs. 121 mmol/l respectively. Patients presented with nausea 44/48, vomiting 28/48, visual disturbance 29/48, apprehension 37/48, disorientation 17/48, breathing difficulties 17/48, and bradycardia 19/21. The earliest observed sign was nausea 21/48, then bradycardia 11/48, apprehension 11/48, and visual disturbance 10/48; after which the procedure was abandoned. None of the patients developed stupor, coma or seizures. Out of the 48 patients, 9 were admitted to high dependency units and all of these were treated with IV furosemide. One patient required a blood transfusion. All patients recovered within 48 hours (range 18-48 hours) and none had any long term complications on follow up. CONCLUSION: The features most associated with the early presentation of TUR syndrome require the patient to be conscious for detection. The use of spinal anaesthesia is therefore desirable to facilitate its early recognition. PMID- 27390577 TI - Critical Manifestations of Pneumoscrotum. AB - INTRODUCTION: Pneumoscrotum is a critical, physical finding that may indicate significant morbidity and mortality. Accumulation of gas in the scrotum can be primary or secondary. OBJECTIVE: This paper discusses rapid diagnosis and treatment options. MATERIAL AND METHODS: PubMed searches for pneumoscrotum, etiology, diagnosis, and treatment. RESULTS: We review the historical perspective, classification, etiology, diagnosis, and treatment options of pneumoscrotum, as well as the presentation of pneumoscrotum in neonates/infants. CONCLUSION: It is crucial to diagnose the etiology pneumoscrotum and designing a treatment option based off that. PMID- 27390578 TI - Oncologic Outcome of Radical Prostatectomy as Monotherapy for Men with High-risk Prostate Cancer. AB - BACKGROUND: The objective of this study was to review our experience with radical prostatectomy (RP) as monotherapy for men with high-risk prostate cancer (PCa). PATIENTS AND METHODS: This study included 382 consecutive patients who were diagnosed with high-risk PCa according to the D'Amico definition and subsequently underwent RP without neoadjuvant therapy. Biochemical recurrence (BR) was defined as a serum prostate-specific antigen (PSA) level >= 0.2 ng/ml on two consecutive measurements, and none of the patients received any adjuvant therapies until their serum PSA levels reached >= 0.4 ng/ml. RESULTS: The median preoperative serum PSA level in these 382 patients was 15.9 ng/ml. Pathological stages >= pT2c and Gleason scores >= 8 were observed in 288 and 194 patients, respectively. During the observation period (median, 48.0 months), BR occurred in 134 patients, and the 5-year BR-free survival rate was 60.1%; however, no patient died of cancer progression. Multivariate analysis identified capsular invasion, seminal vesicle invasion, and surgical margin status as independent predictors of BR. CONCLUSIONS: Comparatively favorable cancer control could be achieved using RP as monotherapy for men with high-risk PCa; however, RP alone may be insufficient for patients with capsular invasion, seminal vesicle invasion, and/or surgical margin positivity. PMID- 27390580 TI - The Efficacy of a Transurethral Incision for Diurnal and Nocturnal Enuresis in Young Males. AB - INTRODUCTION: In this study, we investigated the effects of treatment with a transurethral incision (TUI) for congenital urethral stenosis, which was accompanied by diurnal and nocturnal enuresis. METHODS: We recruited 21 young males who presented to our department for the treatment of diurnal and nocturnal enuresis from January 2010 to March 2014. All patients underwent TUI due to urethral stricture found by a close investigation. We surveyed each case to evaluate the improvement of diurnal and/or nocturnal enuresis after TUI. RESULTS: One and a half years after TUI, an improvement in diurnal enuresis was observed in 17 of 21 cases (80.9%), whereas that of nocturnal enuresis was observe in only 7 of 21 cases (33.3%), showing the significant contribution of TUI to the improvement of diurnal enuresis (p = 0.001). In the case of diurnal enuresis, continual improvement was observed more than a year after surgery, whereas no improvement was observed in nocturnal enuresis at more than 6 months after surgery. CONCLUSION: TUI is more effective for diurnal enuresis than nocturnal enuresis. At postoperative 6 months, clinicians should thus consider other etiologies for unresponsive cases and start other treatment options. PMID- 27390579 TI - The Effect of the Antioxidant Drug "U-74389G" on Creatinine Levels during Ischemia Reperfusion Injury in Rats. AB - OBJECTIVE: The aim of this experimental study was to examine the effect of the antioxidant drug "U-74389G" on a rat model using an ischemia reperfusion protocol. The effect of U-74389G was studied biochemically by measuring mean blood creatinine levels. MATERIALS AND METHODS: Forty rats were used in the study. Creatinine levels were measured at 60 min of reperfusion (groups A and C) or at 120 min of reperfusion (groups B and D), where groups A and B were controls and groups C and D received U-74389G administration. RESULTS: U-74389G administration significantly decreased the predicted creatinine levels by 21.02 +/- 5.06% (p = 0.0001). Reperfusion time non-significantly increased the predicted creatinine levels by 4.20 +/- 6.12% (p = 0.4103). However, U-74389G administration and reperfusion time together produced a significant combined effect in decreasing the predicted creatinine levels by 11.69 +/- 3.16% (p = 0.0005). CONCLUSION: Independent of reperfusion time, U-74389G administration significantly decreased the creatinine levels in an ischemic rat model. This study demonstrates that short-term U-74389G administration improves renal function by increasing creatinine excretion. PMID- 27390581 TI - Chronic Inflammation in Prostate Biopsy Cores is an Independent Factor that Lowers the Risk of Prostate Cancer Detection and is Inversely Associated with the Number of Positive Cores in Patients Elected to a First Biopsy. AB - OBJECTIVES: To investigate associations of chronic inflammatory infiltrate (CII) with prostate cancer (PCa) risk and the number of positive cores in patients elected to a first set of biopsies. MATERIALS AND METHODS: Excluding criteria were as follows: active surveillance, prostate specific antigen (PSA) >= 30 ng/l, re-biopsies, incidental PCa, less than 14 cores, metastases, or 5-alpha reductase inhibitors. The cohort study was classified as negative (control group) and positive cores between 1 and 2 or > 2. RESULTS: The cohort included 421 cases who did not meet the exclusion criteria. PCa was detected in 192 cases (45.6%) of which the number of positive cores was between 1 and 2 in 77 (40.1%) cases. The median PSA was 6.05 ng/ml (range 0.3-29 ng/ml). Linear regression models showed that CII was an independent predictor inversely associated with the risk of PCa. Multinomial logistic regression models showed that CII was an independent factor that was inversely associated with PCa risk in cases with positive cores between 1 and 2 (OR = 0.338; p = 0.004) or more than 2 (OR = 0.076; p < 0.0001) when compared to the control group. CONCLUSION: In a cohort of men undergoing the first biopsy set after prostate assessment, the presence of CII in the biopsy core was an independent factor inversely associated with PCa risk as well as with the number of positive biopsy cores (tumor extension). Clinically, the detection of CII in negative biopsy cores might reduce the risk of PCa in repeat biopsies as well as the probability of detecting multiple positive cores. PMID- 27390582 TI - Intraoperative Frozen Section of the Prostate Reduces the Risk of Positive Margin Whilst Ensuring Nerve Sparing in Patients with Intermediate and High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy: First Reported UK Series. AB - INTRODUCTION: Nerve sparing during robotic radical prostatectomy (RRP) considerably improves post-operative potency and urinary continence as long as it does not compromise oncological outcome. Excision of the neurovascular bundle (NVB) is often performed in patients with intermediate and high risk prostate cancer to reduce the risk of positive surgical margin raising the risk of urinary incontinence and impotence. We present the first UK series outcomes of such patients who underwent an intra-operative frozen section (IOFS) analysis of the prostate during RRP allowing nerve sparing. PATIENTS AND METHODS: We prospectively analysed the data of 40 patients who underwent an IOFS during RRP at our centre from November 2012 until November 2014. Our IOFS technique involved whole lateral circumferential analysis of the prostate during RRP with the corresponding neurovascular tissue. An intrafascial nerve spare was performed and the specimen was removed intra-operatively via an extension of the 12 mm AutosutureTM camera port without undocking robotic arms. It was then painted by the surgeon and sprayed with "Ink Aid" prior to frozen section analysis. The corresponding NVB was excised if the histopathologist found a positive surgical margin on frozen section. RESULTS: Median time to extract the specimen, wound closure and re-establishment of pneumoperitoneum increased the operative time by 8 min. Median blood loss for IOFS was 130 +/- 97 ml vs. 90 +/- 72 ml (p = NS). IOFS was not associated with major complications or with blood transfusion. PSM decreased significantly from non-IOFS RRP series of 28.7 to 7.8% (p < 0.05). Intra-operative PSM on the prostate specimen was seen in 8/40 margin analysis (20%) leading to an excision of the contra-lateral nerve bundle. On analysis of the nerve bundle on a paraffin embedded block, 6 nerve bundle matched tumor on the specimen whereas 2 NVB were retrospectively removed unnecessarily in our series. All 40 patients have undetectable PSA at a mean follow up of 21.2 months (SD 7.79). Functional data at 18 months confirms a reduction in the urinary incontinence from 37% in the IOFS group vs 57% in the non-IOFS group (p = NS). IOFS technique has resulted in a significant increase in intravesical nerve sparing in both T2/T3 patients with intermediate and high risk prostate cancer when appropriately counselled and selected (T2 from 100% in the IOFS group versus 67% and T3 from 100% in the IOFS group to 42%) (p < 0.05). CONCLUSION: Introduction of the IOFS analysis during intrafascial nerve spare RRP has reduced PSM and the rate of urinary incontinence. PMID- 27390583 TI - Painful Bladder Syndrome: An Unusual Presentation in a Case of Upper Tract Fungus Balls. AB - Urinary tract fungus balls are a rare pathologic entity which may be asymptomatic or have variable presentations. To date, there have been no documented cases of fungus balls presenting as painful bladder syndrome. Painful bladder syndrome is a constellation of symptoms which may include pelvic pain, urgency and frequency not explained by other causes. Here, we present the first case of these two entities concurrently. Our patient had a longstanding history of diabetes, nephrolithiasis and recurrent urinary tract infections. He presented with symptoms of painful bladder syndrome and work-up revealed filling defects within the renal collecting system concerning for malignancy. Subsequent ureteroscopy revealed dense white debris consistent with candida fungus balls. Following clearance of the debris and antifungal therapy, our patient has remained asymptomatic. PMID- 27390584 TI - Mullerian Duct Cyst Causing Bladder Outlet Obstruction in a Patient with HNF 1beta Gene Deletion. AB - A 24-year-old male was referred to a tertiary hospital for a possible prostatic abscess. The patient went into acute urinary retention. Transurethral drainage was performed. MRI pelvis three days post-operatively identified the prostatic cystic structure as a mullerian duct cyst. Several other phenotypical features were noted on examination as well as findings on investigations. From these diagnosis of hepatocyte nuclear factor-1beta (HNF-1beta) gene deletion was made. PMID- 27390585 TI - Invasive Squamous Carcinoma and Adenocarcinoma of an Unreconstructed Exstrophic Bladder with HPV Infection. AB - Bladder exstrophy is a complex abnormality and is traditionally treated within the early years of life. It is associated with an increased risk of bladder cancer, with 95% of the arising tumors being adenocarcinomas and 3 to 5% being squamous cell carcinomas. HPV infections are also associated with an increased risk of bladder cancer. This case represents a patient with bladder exstrophy that gave rise to coinciding squamous cell carcinoma and adenocarcinoma. Final pathology results showed an infection with HPV. We presented the management of the case and discussed the diagnosis and treatment methods for this patient. PMID- 27390586 TI - Over-expression of Slc30a8/ZnT8 selectively in the mouse alpha cell impairs glucagon release and responses to hypoglycemia. AB - BACKGROUND: The human SLC30A8 gene encodes the secretory granule-localised zinc transporter ZnT8 whose expression is chiefly restricted to the endocrine pancreas. Single nucleotide polymorphisms (SNPs) in the human SLC30A8 gene have been associated, through genome-wide studies, with altered type 2 diabetes risk. In addition to a role in the control of insulin release, recent studies involving targeted gene ablation from the pancreatic alpha cell (Solomou et al., J Biol Chem 290(35):21432-42) have also implicated ZnT8 in the control of glucagon release. Up to now, however, the possibility that increased levels of the transporter in these cells may impact glucagon secretion has not been explored. METHODS: Here, we use a recently-developed reverse tetracyline transactivator promoter-regulated ZnT8 transgene to drive the over-expression of human ZnT8 selectively in the alpha cell in adult mice. Glucose homeostasis and glucagon secretion were subsequently assessed both in vivo during hypoglycemic clamps and from isolated islets in vitro. RESULTS: Doxyclin-dependent human ZnT8 mRNA expression was apparent in both isolated islets and in fluorescence-activated cell sorting- (FACS) purified alpha cells. Examined at 12 weeks of age, intraperitoneal glucose (1 g/kg) tolerance was unchanged in transgenic mice versus wild-type littermates (n = 8-10 mice/genotype, p > 0.05) and sensitivity to intraperitoneal insulin (0.75U/kg) was similarly unaltered in transgenic animals. In contrast, under hyperinsulinemic-hypoglycemic clamp, a ~45 % (p < 0.001) reduction in glucose infusion rate was apparent, and glucagon release was significantly (~40 %, p < 0.01) impaired, in transgenic mice. Correspondingly, examined in vitro, glucagon secretion was significantly reduced (~30 %, p < 0.05) from transgenic versus control islets at low, stimulatory glucose concentrations (1 mM, p < 0.05) but not at high glucose (17 mM) glucose (p > 0.05). Over expression of ZnT8 in glucagonoma-derived alphaTC1-9 cells increased granule free Zn(2+) concentrations consistent with a role for Zn(2+) in this compartment in the action of ZnT8 on glucagon secretion. CONCLUSIONS: Increased ZnT8 expression, and a likely increase in intragranular free Zn(2+) concentration, is deleterious in pancreatic alpha cells for stimulated glucagon release. These data provide further evidence that type 2 diabetes-associated polymorphisms in the SLC30A8/ZnT8 gene may act in part via alterations in glucagon release and suggest that ZnT8 activation may restrict glucagon release in some settings. PMID- 27390587 TI - Breastfeeding and infant growth outcomes in the context of intensive peer counselling support in two communities in Bangladesh. AB - BACKGROUND: Exclusive breastfeeding and growth faltering during infancy remain challenges in Bangladesh. The Training & Assistance for Health & Nutrition Foundation has been working to address this gap through community-based peer counsellors since 2000. In this paper, we assessed the programme's progress, particularly with respect to early initiation of breastfeeding and exclusive breastfeeding for normal birth weight, as well as for low birth weight (LBW) infants. METHODS: The peer counselling programme is continuing in rural and urban areas of Bangladesh, but only data collected between January 2013 and June 2015 is presented in this descriptive study. Intensive breastfeeding counselling was provided to women during the third trimester of pregnancy and 6 months postpartum by well-trained peer counsellors. They recorded data on infants' birth weight, feeding practices and body weight every month and submitted these for computer entry. Weight measurements were converted to weight-for-age Z-scores (WAZ) and growth patterns assessed by comparing attained body weights with the World Health Organization (WHO) 2006 Child Growth Standards. RESULTS: A total of 994 infants were born during the study period; 94 % were normal birth weight and 6 % were LBW (<2.5 kg). Initiation of breastfeeding within one hour of birth was reported by 94 % of counselled mothers in both groups. The prevalence of exclusive breastfeeding at 6 months was 94 % in the normal birth weight infants and 92 % in the LBW infants, and their mean body weights were 7.5 +/- 0.8 kg and 6.6 +/- 0.7 kg respectively. There was no growth faltering in these infants during 6 months. Underweight rates in normal birth weight infants remained similar (2.2 % at 1 month and 2.5 % at 6 months), whereas underweight rates in LBW infants decreased from 42.1 % at 1 month to 21.1 % at 6 months. CONCLUSIONS: In the context of a well-structured programme setting, and under the described circumstances, it seems likely that the well-trained and supervised community-based peer counsellors could assist in encouraging and helping mothers of both normal birth weight and LBW infants to initiate breastfeeding within one hour and to continue exclusive breastfeeding until 6 months of age. Our data suggest that they may also have contributed towards prevention of growth faltering in these infants. PMID- 27390588 TI - Assessing the quality of Smilacis Glabrae Rhizoma (Tufuling) by colormetrics and UPLC-Q-TOF-MS. AB - BACKGROUND: The quality of the materials used in Chinese medicine (CM) is generally assessed based on an analysis of their chemical components (e.g., chromatographic fingerprint analysis). However, there is a growing interest in the use of color metrics as an indicator of quality in CM. The aim of this study was to investigate the accuracy and feasibility of using color metrics and chemical fingerprint analysis to determine the quality of Smilacis Glabrae Rhizoma (Tufuling) (SGR). The SGR samples were divided into two categories based on their cross-sectional coloration, including red SGR (R-SGR) and white SGR (W SGR). METHODS: Forty-three samples of SGR were collected and their colors were quantized based on an RGB color model using the Photoshop software. An ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF MS) system was used for chromatographic fingerprint analysis to evaluate the quality of the different SGR samples. Hierarchical cluster analysis and dimensional reduction were used to evaluate the data generated from the different samples. Pearson correlation coefficient was used to evaluate the relationship between the color metrics and the chemical compositions of R-SGR and W-SGR. RESULTS: The SGR samples were divided into two different groups based on their cross-sectional color, including color A (CLA) and B (CLB), as well as being into two separate classes based on their chemical composition, including chemical A (CHA) and B (CHB). Standard fingerprint chromatograms were for CHA and CHB. Statistical analysis revealed a significant correlation (Pearson's r = 0.769, P < 0.001) between the color metrics and the results of the chemical fingerprint analysis. CONCLUSIONS: The SGR samples were divided into two major clusters, and the variations in the colors of these samples reflected differences in the quality of the SGR material. Furthermore, we observed a statistically significant correlation between the color metrics and the quality of the SGR material. PMID- 27390590 TI - An investigation to assess ankle mobility in healthy individuals from the application of multi-component compression bandages and compression hosiery. AB - BACKGROUND: An investigation was undertaken to compare the effect of multi component compression bandages and compression hosiery kits on individuals' range of ankle motion whilst wearing typical and medical footwear, and barefoot. METHODS: A convenience sample of 30 healthy individuals recruited from the staff and student population at the University of Huddersfield, UK. Plantarflexion/dorsiflexion range of ankle motion (ROAM) was measured in participants over 6 steps in every combination of typical, medical and no footwear; and multi-component bandages, compression hosiery and no garments. RESULTS: Controlling for age, gender and garments, the use of typical footwear was associated with a mean increase in ROAM of 2.54 degrees at best estimate compared with barefoot; the use of medical footwear was associated with a mean decrease in ROAM of 1.12 degrees at best estimate compared with barefoot. Controlling for age, gender and footwear, the use of bandaging was associated with a mean decrease in ROAM of 2.51 degrees at best estimate compared with no garments. Controlling for age, gender and footwear, the use of hosiery was not associated with a significant change in ROAM compared with no garments. CONCLUSIONS: Bandages appear to restrict ROAM more than hosiery when used in conjunction with a variety of footwear types. PMID- 27390589 TI - Improving total saccharification yield of Arabidopsis plants by vessel-specific complementation of caffeoyl shikimate esterase (cse) mutants. AB - BACKGROUND: Caffeoyl shikimate esterase (CSE) was recently characterized as an enzyme central to the lignin biosynthetic pathway in Arabidopsis thaliana. The cse-2 loss-of-function mutant shows a typical phenotype of lignin-deficient mutants, including collapsed vessels, reduced lignin content, and lignin compositional shift, in addition to a fourfold increase in cellulose-to-glucose conversion when compared to the wild type. However, this mutant exhibits a substantial developmental arrest, which might outweigh the gains in fermentable sugar yield. To restore its normal growth and further improve its saccharification yield, we investigated a possible cause for the yield penalty of the cse-2 mutant. Furthermore, we evaluated whether CSE expression is under the same multi-leveled transcriptional regulatory network as other lignin biosynthetic genes and analyzed the transcriptional responses of the phenylpropanoid pathway upon disruption of CSE. RESULTS: Transactivation analysis demonstrated that only second-level MYB master switches (MYB46 and MYB83) and lignin-specific activators (MYB63 and MYB85), but not top-level NAC master switches or other downstream transcription factors, effectively activate the CSE promoter in our protoplast-based system. The cse-2 mutant exhibited transcriptional repression of genes upstream of CSE, while downstream genes were mainly unaffected, indicating transcriptional feedback of CSE loss-of-function on monolignol biosynthetic genes. In addition, we found that the expression of CSE under the control of the vessel-specific VND7 promoter in the cse-2 background restored the vasculature integrity resulting in improved growth parameters, while the overall lignin content remained relatively low. Thus, by restoring the vascular integrity and biomass parameters of cse-2, we further improved glucose release per plant without pretreatment, with an increase of up to 36 % compared to the cse-2 mutant and up to 154 % compared to the wild type. CONCLUSIONS: Our results contribute to a better understanding of how the expression of CSE is regulated by secondary wall-associated transcription factors and how the expression of lignin genes is affected upon CSE loss-of-function in Arabidopsis. Moreover, we found evidence that vasculature collapse is underlying the yield penalty found in the cse-2 mutant. Through a vessel-specific complementation approach, vasculature morphology and final stem weight were restored, leading to an even higher total glucose release per plant. PMID- 27390592 TI - Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma. AB - BACKGROUND: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells. METHODS: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence free survivals were assessed. RESULTS: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7(th) edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence free survival (P = 0.017; P = 0.015). CONCLUSIONS: The upregulation of TRPA1 protein level is frequently correlated to unfavorable prognosticators and gives rise to cancer progression in NPC patients. PMID- 27390591 TI - Germline modification of domestic animals. AB - Genetically-modified domestic animal models are of increasing significance in biomedical research and agriculture. As authentic ES cells derived from domestic animals are not yet available, the prevailing approaches for engineering genetic modifications in those animals are pronuclear microinjection and somatic cell nuclear transfer (SCNT, also known as cloning). Both pronuclear microinjection and SCNT are inefficient, costly, and time-consuming. In animals produced by pronuclear microinjection, the exogenous transgene is usually inserted randomly into the genome, which results in highly variable expression patterns and levels in different founders. Therefore, significant efforts are required to generate and screen multiple founders to obtain animals with optimal transgene expression. For SCNT, specific genetic modifications (both gain-of-function and loss-of function) can be engineered and carefully selected in the somatic cell nucleus before nuclear transfer. SCNT has been used to generate a variety of genetically modified animals such as goats, pigs, sheep and cattle; however, animals resulting from SCNT frequently suffer from developmental abnormalities associated with incomplete nuclear reprogramming. Other strategies to generate genetically modified animals rely on the use of the spermatozoon as a natural vector to introduce genetic material into the female gamete. This sperm mediated DNA transfer (SMGT) combined with intracytoplasmatic sperm injection (ICSI) has relatively high efficiency and allows the insertion of large DNA fragments, which, in turn, enhance proper gene expression. An approach currently being developed to complement SCNT for producing genetically modified animals is germ cell transplantation using genetically modified male germline stem cells (GSCs). This approach relies on the ability of GSCs that are genetically modified in vitro to colonize the recipient testis and produce donor derived sperm upon transplantation. As the genetic change is introduced into the male germ line just before the onset of spermatogenesis, the time required for the production of genetically modified sperm is significantly shorter using germ cell transplantation compared to cloning or embryonic stem (ES) cell based technology. Moreover, the GSC-mediated germline modification circumvents problems associated with embryo manipulation and nuclear reprogramming. Currently, engineering targeted mutations in domestic animals using GSCs remains a challenge as GSCs from those animals are difficult to maintain in vitro for an extended period of time. Recent advances in genome editing techniques such as Zinc-Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) greatly enhance the efficiency of engineering targeted genetic change in domestic animals as demonstrated by the generation of several gene knock-out pig and cattle models using those techniques. The potential of GSC-mediated germline modification in making targeted genetic modifications in domestic animal models will be maximized if those genome editing techniques can be applied in GSCs. PMID- 27390593 TI - Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 Suppresses Proliferation and Induces Apoptosis in Non-Small-Cell Lung Cancer. AB - Our previous studies demonstrated that depletion of tubulin polymerization promoting protein family member 3 (TPPP3) inhibits proliferation and induces apoptosis of HeLa cells. However, the expression and roles of TPPP3 in cancers remain largely unknown. In this study, we investigated the expression of TPPP3 in clinicopathological correlations in non-small-cell lung cancer (NSCLC) samples by immunohistochemistry. TPPP3 expression was significantly upregulated in NSCLC tissues, and high TPPP3 expression was positively associated with tumor size, lymph node metastasis, clinical stage, and poor survival. Furthermore, knockdown of TPPP3 by shRNA significantly inhibited cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. In addition, depletion of TPPP3 inhibited lung cancer growth in vivo in the xenografts of H1299 cells; this effect was accompanied by the suppression of Ki67 expression. Our data suggested that TPPP3 might act as an oncogene in NSCLC. TPPP3 warrants consideration as a therapeutic candidate with anti-tumor potential. PMID- 27390594 TI - CPA4 is a Novel Diagnostic and Prognostic Marker for Human Non-Small-Cell Lung Cancer. AB - Background. Carboxypeptidase A4 (CPA4) belongs to a member of the metallocarboxypeptidase family, and its expression in lung cancer samples and clinical significance are still not investigated until now. In this study, we aimed to evaluate the level of CPA4 in non-small-cell lung cancer (NSCLC) samples and correlate its level with clinical outcome. Methods. CPA4 gene expression in lung cancer tissues were analyzed by using the Oncomine database (www.oncomine.org). The expression of CPA4, Survivin and VEGF in lung cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on two different commercial tissue arrays (Shanghai Biochip Co., Ltd., Shanghai, China). Their levels in serum were determined by using commercial human enzyme-linked immunosorbent assay kits. We also examined their relations to clinicopathologic parameters, and explored the diagnostic and prognostic value in NSCLC. Results. We identified an elevation of CPA4 in mRNA level and gene amplification in lung cancer tissues in comparison to normal lung tissues. High CPA4 expression was observed in 120/165 (72.7%) NSCLC samples, and significantly correlated with Tumor size, Depth of invasion, Lymph Node Metastasis, Stage, VEGF level and Survivin level. High CPA4 expression is associated with poor prognosis of NSCLC patients. Multivariable Cox regression analysis demonstrated that CPA4 expression was an independent prognostic factor. Furthermore, serum CPA4 level was also significantly higher in NSCLC patients than in healthy controls. Logistic regression analysis revealed that serum CPA4 and CYFRA21-1 level were the significant parameters for detecting NSCLC. Receiver operating characteristic curves (ROC) in NSCLC patients versus normal people yielded the optimal cut-off value was 2.70 ng/ml for CPA4 and 19 ng/ml for CYFRA21-1, respectively. The area under ROC curve (AUC) was 0.830 for the combination of the two tumor markers. Conclusion. Our results demonstrated that overexpression of CPA4 in NSCLC is associated with an unfavorable prognosis, and serum CPA4 level combining with serum CYFRA21-1 level could be used to aid early detection of NSCLC. PMID- 27390595 TI - MET Inhibition in Clear Cell Renal Cell Carcinoma. AB - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. METHODS: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. RESULTS: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. CONCLUSIONS: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. PMID- 27390596 TI - Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas. AB - BACKGROUND AND AIMS: Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. METHODS: Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. RESULTS: There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better prognosis was found in the cases with low microvessel density (MVD) in tumor tissue and high expression of SPARC (SPARC>=5%) in stromal cells. CONCLUSIONS: "Double-hit" lymphoma was rare among primary gastric lymphoma, while patients with multiple gene amplification and/or copy gains of c-Myc, bcl2 and bcl6, and "double-protein" gastric B-cell lymphomas had a poor clinical outcome. In addition, patients with MYC, BCL2 and BCL6 expression negative or low MVD in tumor tissue with high expression of SPARC in stromal cells could have better prognosis than other gastric B-cell lymphomas regardless of their clinical stage and pathological types. These results would be of very importance for clinical stratified management and precision medicine of gastric B-cell lymphomas. PMID- 27390597 TI - Reduced Expression of FADS1 Predicts Worse Prognosis in Non-Small-Cell Lung Cancer. AB - OBJECTIVE: Fatty acid desaturase 1 is a member of the fatty acid desaturase, which is related to a number of diseases. However, its role in cancers remains unclear. This study was to explore the clinical importance of FADS1 expression in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Immunochemistry was used to evaluate FADS1 expressions in 216 paraffin-embedded specimens. The expression of FADS1 was divided into high and low groups. The clinical and prognostic significance of FADS1 expression was analyzed statistically by Kaplan Meier estimate and Cox regression model. RESULTS: FADS1 overexpressed in normal bronchial mucosa compared with non-small-cell lung cancer. Reduced FADS1 expression was associated with tumor size (P=0.023) and histological grade (P<0.0001). Patients with lower expression of FADS1 had shorter overall survival and disease free survival (P=0.001 and P=0.002). Multivariate analysis showed FADS1 expression was an independent prognostic factor in NSCLC (P=0.011). CONCLUSION: Reduced expression of FADS1 suggests pessimistic prognosis for NSCLC patients. Further studies are warranted. PMID- 27390599 TI - Comparison of Uncinate Process Cancer and Non-Uncinate Process Pancreatic Head Cancer. AB - The special anatomical position accounts for unusual clinicopathological features of uncinate process cancer. This study aimed to compare clinicopathological features of patients with uncinate process cancer to patients with non-uncinate process pancreatic head cancer. Total 160 patients with pancreatic head cancer were enrolled and classified into two groups: uncinate process cancer and non uncinate process pancreatic head cancer. We found that the ratio of vascular invasion was significantly higher in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In addition, the rate of R1 resection was significantly higher in patients with uncinate process cancer. Furthermore, the median disease-free survival (11 months vs. 15 months, p=0.043) and overall survival (15 months vs. 19 months, p=0.036) after R0 resection were lower for uncinate process cancer. Locoregional recurrence was more frequent (p=0.017) and earlier (12 months vs. 36 months; p=0.002) in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In conclusion, uncinate process cancer is more likely to invade blood vessel and has worse prognosis due to the earlier and more frequent locoregional recurrence. PMID- 27390598 TI - The Role of Mir-148a in Cancer. AB - MicroRNAs (miRNAs) are highly conserved noncoding RNAs of about 19-25 nucleotides. Through specifically pairing with complementary sites in 3' untranslated regions (UTRs) of target mRNAs, they mediate post-transcriptional silencing. MicroRNAs have been implicated in many physiological processes including proliferation, differentiation, development, apoptosis, and metabolism. In recent years many studies have revealed that the aberrant expression of miRNA is closely related to oncogenesis and is now an intense field of study. Mir-148a is aberrantly expressed in various cancers and has been identified as an oncogenic or tumor suppressor with crucial roles in the molecular mechanisms of oncogenesis. In this review, we have summarized the role of mir-148a in the oncogenic pathways of gastric, liver, breast and urogenital cancers, and in neurogliocytoma oncogenesis. Studying the functional role of mir-148a is crucial in discovering novel tumor molecular markers and identifying potential therapeutic targets. PMID- 27390600 TI - Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells. AB - We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer. PMID- 27390601 TI - LncRNAs and Esophageal Squamous Cell Carcinoma - Implications for Pathogenesis and Drug Development. AB - LncRNAs are a group of ncRNA species longer than 200 nt, which have fundamental regulatory roles in diverse cellular processes and diseases progression. Esophageal cancer is a serious malignancy with respect to prognosis and mortality rate. It is among the five leading cancer types for the cancer deaths in males of middle age in the United States. In China, esophageal cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death. The molecular mechanisms of esophageal cancer development are not fully understood, but emerging studies point out that lncRNAs may actively associate with the pathogenesis. In this review, we first provided an introduction of lncRNAs classifications. Then we focused on the recent findings on lncRNA expression and function in esophageal cancer development. Implications for pathogenesis and potential drug developments will also be discussed. PMID- 27390602 TI - Use of Plasma Metabolomics to Identify Diagnostic Biomarkers for Early Stage Epithelial Ovarian Cancer. AB - The early detection of ovarian carcinoma is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. The currently available biomarkers (such as CA125 and HE4) are insufficiently reliable to distinguish early stage (I/II) epithelial ovarian cancer (EOC) patients from normal individuals because they possess a relatively poor sensitivity and specificity. To evaluate the application of metabolomics to biomarker discovery in the early stages of epithelial ovarian cancer (EOC), plasma samples from 21 early stage EOC patients and 31 healthy controls were analyzed with ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof/MS) in conjunction with multivariate statistical analysis. Eighteen metabolites, including lysophospholipids, 2-piperidone and MG (18:2), were found to be disturbed in early stage EOC with satisfactory diagnostic accuracy (AUC=0.920). These biomarkers were specifically validated in the EOC nude mouse model, and five of the biomarkers (lysophospholipids, adrenoyl ethanolamide et al.) were highly suspected of being associated with EOC because they were differentially expressed with the same tendency in the EOC nude mice versus normal controls. In conclusion, the selected metabolic biomarkers have considerable utility and significant potential for diagnosing early ovarian cancer and investigating its underlying mechanisms. PMID- 27390603 TI - Association between the OGG1 Ser326Cys Polymorphism and Cancer Risk: Evidence from 152 Case-Control Studies. AB - Although it has been suggested that the 8-oxoguanine DNA glycosylase (OGG1) gene Ser326Cys polymorphism may be a risk factor for cancer, the conclusions from previous studies are inconsistent. Thus, we conducted an updated meta-analysis to estimate the effect of OGG1 variant genotypes on cancer susceptibility. We searched the PubMed for all eligible studies published in English for the period ending September 2014. We found the association between OGG1 Ser326Cys polymorphism and cancer susceptibility based on 152 case-control studies in different genetic model comparisons (dominant model: OR = 1.053, P = 0.018; recessive model: OR = 1.108, P < 0.001; homozygote: OR = 1.135, P < 0.001; additive model: OR = 1.059, P < 0.001). However, the results from the subgroup analyses based on types of cancer, health population as controls or studies with relatively large sample size did not support the conclusion. Although the overall results of this meta-analysis showed a positive association between OGG1 variant genotypes and cancer susceptibility, the subgroup analyses by cancer type, sample size, and source of controls presented inconsistent results. Therefore, the current evidence from the meta-analysis did not support the hypothesis of OGG1 Ser326Cys polymorphism as a risk factor of cancer. PMID- 27390605 TI - Increased Expression of Several Collagen Genes is Associated with Drug Resistance in Ovarian Cancer Cell Lines. AB - Ovarian cancer is the most lethal gynaecological cancer. The main reason for the high mortality among ovarian cancer patients is the development of drug resistance. The expression of collagen genes by cancer cells can increase drug resistance by inhibiting the penetration of the drug into the cancer tissue as well as increase apoptosis resistance. In this study, we present data that shows differential expression levels of collagen genes and proteins in cisplatin- (CIS), paclitaxel- (PAC), doxorubicin- (DOX), topotecan- (TOP), vincristine- (VIN) and methotrexate- (MTX) resistant ovarian cancer cell lines. Quantitative real-time polymerase chain reactions were performed to determine the mRNA levels. Protein expression was detected using Western blot and immunocytochemistry assays. In the drug resistant cell lines, we observed the upregulation of eight collagen genes at the mRNA level and based on these expression levels, we divided the collagen genes into the following three groups: 1. Genes with less than a 50 fold increase in expression: COL1A1, COL5A2, COL12A1 and COL17A1. 2. Genes with greater than a 50-fold increase in expression: COL1A2, COL15A1 and COL21A1. 3. Gene with a very high level of expression: COL3A1. Expression of collagen (COL) proteins from groups 2 and 3 were also confirmed using immunocytochemistry. Western blot analysis showed very high expression levels of COL3A1 protein, and immunocytochemistry analysis showed the presence of extracellular COL3A1 in the W1TR cell line. The cells mainly responsible for the extracellular COL3A1 production are aldehyde dehydrogenase-1A1 (ALDH1A1) positive cells. All correlations between the types of cytostatic drugs and the expression levels of different COL genes were studied, and our results suggest that the expression of fibrillar collagens may be involved in the TOP and PAC resistance of the ovarian cancer cells. The expression pattern of COL genes provide a preliminary view into the role of these proteins in cytostatic drug resistance of cancer cells. The exact role of these COL genes in drug resistance requires further investigation. PMID- 27390606 TI - Clinical Efficacy of Ovarian Cancer Screening. AB - Various trials of ovarian cancer screening programs have been reported worldwide. In 2011, one of the most famous papers indicated that annual screening using CA125/transvaginal sonography (TVS) did not reduce ovarian cancer mortality in the United States of America (USA). To investigate the validity of ovarian cancer screening, we verified the analyses of previous reports. At first, we obtained the USA datasets that were used for the analyses and identified many patients in whom cancers were accidentally detected several years after the screening period. We thus performed a new prognostic comparison between the screening group (cancers that were detected through screening or within one year after screening) and the control group (cancers that were found more than one year after screening, without screening, or in the original control group). The results showed that the prognoses of the screening group were significantly better than those of the control group (p=0.0017). In addition, the screening group contained significantly fewer stage IV cases than the control group (p=0.005). In another screening in the United Kingdom, ovarian cancer was detected at a relatively earlier stage (stage I/II: 44%), while the rate of stage IV detection was low (4%). Very recently, this team showed significant difference in the rates with and without screening (p=0.021) when prevalent cases were excluded and indicated the delayed effect of screening. These results contrasted with the USA data. In other studies in the USA and Japan, annual screening was also associated with a decreased stage at detection. New histopathological, molecular and genetic studies have recently provided two categories of ovarian carcinogenesis. Type I carcinomas are slow-growing neoplasms that often develop from benign ovarian cysts. Type II carcinomas are high-grade clinically aggressive neoplasms. The rate of type II carcinomas is significantly higher in Europe and the USA than in Asia (p<0.001). Conversely, type I carcinomas are relatively common in Asia. These data theoretically imply that annual screening would be more effective in Asia. PMID- 27390607 TI - Multi-target siRNA: Therapeutic Strategy for Hepatocellular Carcinoma. AB - Multiple targets RNAi strategy is a preferred way to treat multigenic diseases, especially cancers. In the study, multi-target siRNAs were designed to inhibit NET-1, EMS1 and VEGF genes in hepatocellular carcinoma (HCC) cells. And multi target siRNAs showed better silencing effects on NET-1, EMS1 and VEGF, compared with single target siRNA. Moreover, multi-target siRNA showed greater suppression effects on proliferation, migration, invasion, angiogenesis and induced apoptosis in HCC cells. The results suggested that multi-target siRNA might be a preferred strategy for cancer therapy and NET-1, EMS1 and VEGF could be effective targets for HCC treatments. PMID- 27390604 TI - Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. AB - Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID- 27390609 TI - Serum Adiponectin Level May be an Independent Predictor of Clear Cell Renal Cell Carcinoma. AB - OBJECTIVES: To examine whether serum adiponectin or leptin level has the ability to differentiate clear cell renal cell carcinoma (ccRCC) from other subtypes of renal cell carcinoma (RCC) in a Chinese population. PATIENTS AND METHODS: We recruited 198 consecutive patients who were treated with radical or partial nephrectomy in our department from September 2011 to June 2013. Their histological types were all malignant, including clear cell, papillary, chromophobe and unclassified RCC. We also enrolled 86 people with no cancer or cancer-related diseases as normal controls. We measured patients' preoperative blood samples for plasma adiponectin and leptin concentrations using an enzyme linked immunosorbent assay method. Statistical methods were used to analyze ccRCC and other subtypes as they relate to serum adiponectin/leptin level and other factors such as body mass index or visceral fat area. RESULTS: In our database, normal controls had significantly higher circulating adiponectin (p < 0.001) and leptin levels (p < 0.001) than patients with RCC. Among the 198 RCC patients, 156 patients had ccRCC while 42 patients had other histological types. Serum adiponectin levels were lower in ccRCC patients than in non-clear-cell RCC patients (p = 0.004). However, the plasma leptin level was not differently distributed between ccRCC and non-ccRCC patients (p = 0.940). In multivariate analysis, we found that serum adiponectin level may be an independent predictor for discriminating ccRCC patients from others (p = 0.004). Furthermore, in the ccRCC subgroup, we observed that men with ccRCC had lower leptin (p < 0.001) and adiponectin (p = 0.002) levels, and diabetic patients had lower plasma adiponectin levels (p = 0.001). CONCLUSIONS: Lower plasma adiponectin concentration was related to an increased incidence of ccRCC and may act as an independent predictor for ccRCC. Our study may help define the process from obesity to adipose tissue, to cytokines and finally to ccRCC. PMID- 27390610 TI - Tailored Selection of First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma of Bladder. AB - PURPOSE: Methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) and gemcitabine plus cisplatin (GC) are both effective first-line chemotherapy. We explore the responsive variables of MVAC and GC for patients with metastatic urothelial carcinoma of bladder (mUCB). MATERIALS AND METHODS: Patients who were initially diagnosed to have mUCB and received MVAC or GC as metastatic first-line chemotherapy between 2000 and 2014 at Kaohsiung Chang Gung Memorial Hospital were reviewed. Totally, 130 patients were enrolled into our study. Univariable Cox proportional hazard models were constructed for OS. Hazard ratio (HR) and 95% confidence intervals (CIs) was also presented. RESULTS: There were 50 patients (38%) in the MVAC group and 80 patients (62%) in the GC group. The median OS was insignificantly different between MVAC and GC groups, accounting for 17.0 and 14.4 months (P = 0.214), respectively. OS of MVAC group was significantly longer with regard to age ? 60 years (HR: 0.38, 95% CI: 0.12-0.97, P = 0.036), pure urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015), > 1 metastatic sites (HR: 0.19, 95% CI: 0.08-0.44, P = < 0.001), and neutrophil to lymphocyte ratio > 3(HR: 0.45, 95% CI: 0.25-0.81, P = 0.006), while OS with GC group was significantly longer with regard to variant urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015). CONCLUSIONS: Our study disclosed the predictive factors of different regimen for mUCB. These results have clinical implication for physicians who treat patients with mUCB. PMID- 27390608 TI - Pancreatic Cancer from Molecular Pathways to Treatment Opinion. AB - Pancreatic cancer is considered one of the most lethal malignances. It has been observed that the five year survival rate is less than 5%. Early diagnosis, understanding the risk factors and investigation of the molecular pathways with targeted therapy are the keys for efficient treatment. Moreover; there are several local treatments for patients with unresectable pancreatic cancer. There are several combined therapies with chemotherapy and radiotherapy, however; a local therapy approach for many patients with poor performance status are in need. For those patients with good performance status new polychemotherapy regimens are used with success and increased survival improvement. Polychemotherapy has been observed to increase the rate of radical resections in some cases. Second line therapy is used for patients with good performance status and metastatic disease. Oxaliplatin-based regimens are mostly used, however; there are several other drugs that are being developed. Unfortunately, targeted therapy has not presented the expected efficiency. Moreover; immunotherapy; another treatment approach for several cancers types has again failed to present positive results for pancreatic cancer. In the current mini review, we will present information from the diagnosis to molecular pathways and targeted treatment. PMID- 27390611 TI - Should All Nasopharyngeal Carcinoma with Paranasal Sinus Invasion Be Staged as T3 in the Intensity-Modulated Radiotherapy Era? A Study of 1811 Cases. AB - BACKGROUND: Currently, there is no uniform consensus regarding the appropriate staging for invasion of the paranasal sinuses in nasopharyngeal carcinoma (NPC). In the current AJCC staging system for NPC, paranasal sinus invasion is defined within the T3 classification. However, according to the Chinese 2008 staging system, which is also widely used in the regions where NPC is endemic in China, paranasal sinus invasion is classified as T4 disease. METHODS: Patients (n = 1811) with non-metastatic, histologically-proven NPC treated with intensity modulated radiotherapy (IMRT) were retrospectively analyzed. RESULTS: Paranasal sinus invasion was identified in 289/1811 patients (16.0%). Multivariate analysis revealed ethmoid sinus invasion (HR, 2.889; 95% CI, 1.362-6.131; P = 0.006) and maxillary sinus invasion (HR, 3.110; 95% CI, 1.439-6.721; P = 0.004) were independent prognostic factors for local relapse-free survival (LRFS). T3 patients with ethmoid sinus or maxillary sinus invasion had similar 3-year LRFS (83.6% vs. 92.2%, P = 0.132) as T4 patients, and had poorer LRFS (83.6% vs. 98.3%, P = 0.006) than T3 patients with sphenoid sinus invasion alone. Also, T3 patients with sphenoid sinus invasion alone had similar 3-year LRFS (98.3 vs. 96.4%, P = 0.391) as T3 patients without paranasal sinus invasion, and a trend toward higher LRFS (98.3% vs. 92.2%, P = 0.065) than T4 patients. CONCLUSION: In patients underwent IMRT, tumors with ethmoid sinus or maxillary sinus invasion had a higher risk of local failure than those with sphenoid sinus invasion alone. Sphenoid sinus invasion alone should be classified as T3 disease and ethmoid sinus or maxillary sinus involvement as T4 disease in the current AJCC staging system for NPC. PMID- 27390612 TI - Transduction of Recombinant M3-p53-R12 Protein Enhances Human Leukemia Cell Apoptosis. AB - Tumor suppressor protein p53 plays important roles in initiating cell cycle arrest and promoting tumor cell apoptosis. Previous studies have shown that p53 is either mutated or defective in approximately 50% of human cancers; therefore restoring normal p53 activity in cancer cells might be an effective anticancer therapeutic approach. Herein, we designed a chimeric p53 protein flanked with the MyoD N-terminal transcriptional activation domain (amino acids 1-62, called M3) and a poly-arginine (R12) cell penetrating signal in its N-and C-termini respectively. This chimeric protein, M3-p53-R12, can be expressed in E. coli and purified using immobilized metal ion chromatography followed by serial refolding dialysis. The purified M3-p53-R12 protein retains DNA-binding activity and gains of cell penetrating ability. Using MTT assay, we demonstrated that M3-p53-R12 inhibited the growth of K562, Jurkat as well as HL-60 leukemia cells carrying mutant p53 genes. Results from FACS analysis also demonstrated that transduction of M3-p53-R12 protein induced cell cycle arrest of these leukemia cells. Of special note, M3-p53-R12 has no apoptotic effect on normal mesenchymal stem cells (MSC) and leukocytes, highlighting its differential effects on normal and tumor cells. To sum up, our results reveal that purified recombinant M3-p53-R12 protein has functions of suppressing the leukemia cell lines' proliferation and launching cell apoptosis, suggesting the feasibility of using M3-p53-R12 protein as an anticancer drug. In the future we will test whether this chimeric protein can preferentially trigger the death of malignant cancer cells without affecting normal cells in animals carrying endogenous or xenographic tumors. PMID- 27390614 TI - Is there a Link Between Foreclosure and Health? AB - We investigate the relationship between foreclosures and hospital visits using data on all foreclosures and all hospital and emergency room visits from four states that were among the hardest hit by the foreclosure crisis. We find that living in a neighborhood with a spike in foreclosures is associated with significant increases in urgent unscheduled visits, including increases in visits for preventable conditions. The estimated relationships cannot be accounted for by increasing unemployment, declines in housing prices, migration, or by people switching from out-patient providers to hospitals. PMID- 27390613 TI - Bilayer of Terbium Double-Decker Single-Molecule Magnets. AB - We report a low-temperature scanning tunneling microscopy and spectroscopy study of the structural and electronic properties of a bilayer of terbium double-decker (bis(phthalocyaninato)terbium(III), TbPc2) molecules on Au(111) at 5 K. The TbPc2 molecules are found to adsorb flat on top of a first compact TbPc2 monolayer on Au(111), forming a square-like packing similar to the underlying first layer. Their frontier-orbital electronic structure, measured by tunneling conductance spectroscopy, clearly differs from that of the underlying first monolayer. Our results of second-layer molecules indicate the absence of, both, hybrid molecule substrate electronic states close to the Fermi level and a zero-bias Kondo resonance. We attribute these findings to a decreased electronic coupling with the Au(111) substrate. PMID- 27390615 TI - PHENOTYPIC CHARACTERIZATION OF BREAST INVASIVE CARCINOMA VIA TRANSFERABLE TISSUE MORPHOMETRIC PATTERNS LEARNED FROM GLIOBLASTOMA MULTIFORME. AB - Quantitative analysis of whole slide images (WSIs) in a large cohort may provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical variations (e.g., fixation, staining) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. Although unsupervised feature learning provides a promising way in learning pertinent features without human intervention, its capability can be greatly limited due to the lack of well-curated examples. In this paper, we explored the transferability of knowledge acquired from a well curated Glioblastoma Multiforme (GBM) dataset through its application to the representation and characterization of tissue histology from the Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Our experimental results reveals two major phenotypic subtypes with statistically significantly different survival curves. Further differential expression analysis of these two subtypes indicates enrichment of genes regulated by NF-kB in response to TNF and genes up regulated in response to IFNG. PMID- 27390616 TI - Conceptualization of Idle (Laghw) and its relation to medical futility. AB - A major debate in medical ethics is the request for futile treatment. The topic of medical futility requires discrete assessment in Iran for at least two reasons. First, the common principles and foundations of medical ethics have taken shape in the context of Western culture and secularism. Accordingly, the implementation of the same guidelines and codes of medical ethics as Western societies in Muslim communities does not seem rational. Second, the challenges arising in health service settings are divergent across different countries. The Quranic concept of idle (laghw) and its derivatives are used in 11 honorable verses of the Holy Quran. Among these verses, the 3rd verse of the blessed Al Muminun Surah was selected for its closer connection to the concept under examination. The selected verse was researched in the context of all dictionaries presented in Noor Jami' al-Tafasir 2 (The Noor Collection of Interpretations 2) software. "Idle" is known as any insignificant speech, act, or thing that is not beneficial; an action from which no benefit is gained; any falsehood (that is not stable or realized); an entertaining act; any foul, futile talk and action unworthy of attention; loss of hope; and something that is not derived from method and thought. The word has also been used to refer to anything insignificant. The notes and derived interpretations were placed in the following categories: A) Having no significant benefit (When medical care does not benefit the patient (his body and/or soul and his life in this world and/or the Hereafter), it is wrong to proceed with that medical modality; B) Falsehood (Actions that fail to provide, maintain, and improve health are clearly futile); C) Unworthy of attention (An action that neither improves health nor threatens it is wrong and impermissible). PMID- 27390617 TI - The paradigm model of distorted doctor-patient relationship in Southern Iran: a grounded theory study. AB - The doctor-patient relationship (DPR) is one of the most important subjects in medical sociology and health policy. Due to mutual understanding, undistorted DPRs not only result in satisfaction of both doctors and patients, but also help to reduce financial burdens for patients and the health care system. The purpose of this research was to identify a DPR based on the qualitative paradigm model which is called the grounded theory (GT) methodology. The data were collected from 3 focus groups, the participants of which consisted of 21 faculty members of Shiraz University of Medical Sciences, Shiraz, Iran. The content of the interviews, following the transcription stage, was organized based on open, axial, and selective coding. Results showed that DPR was distorted which was the consequence of an inefficient structure in the healthcare system which is related to several cultural barriers. In this situation, agency is determinant so the doctor's personality determines the direction of DPR. Consequences of such scenarios are the patient's distrust, patient's dissatisfaction, lack of mutual understanding, patient suppression, and patient deception. Therefore, the health care system should emphasize on reforming its inefficient infrastructures, so that, besides being controlled and surveyed, physicians are socialized ethically. PMID- 27390619 TI - Triple-helical collagen hydrogels via covalent aromatic functionalization with 1,3-Phenylenediacetic acid. AB - Chemical crosslinking of collagen is a general strategy to reproduce macroscale tissue properties in physiological environment. However, simultaneous control of protein conformation, material properties and biofunctionality is highly challenging with current synthetic strategies. Consequently, the potentially diverse clinical applications of collagen-based biomaterials cannot be fully realised. In order to establish defined biomacromolecular systems for mineralised tissue applications, type I collagen was functionalised with 1,3 Phenylenediacetic acid (Ph) and investigated at the molecular, macroscopic and functional levels. Preserved triple helix conformation was observed in obtained covalent networks via ATR-FTIR (AIII/A1450 ~ 1) and WAXS, while network crosslinking degree (C: 87-99 mol.-%) could be adjusted based on specific reaction conditions. Decreased swelling ratio (SR: 823-1285 wt.-%) and increased thermo-mechanical (Td : 80-88 degrees C; E: 28-35 kPa; sigmamax : 6-8 kPa; epsilonb : 53-58 %) properties were observed compared to state-of-the-art carbodiimide (EDC)-crosslinked collagen controls, likely related to the intermolecular covalent incorporation of the aromatic segment. Ph-crosslinked hydrogels displayed nearly intact material integrity and only a slight mass decrease (MR : 5-11 wt. %) following 1-week incubation in either PBS or simulated body fluid (SBF), in contrast to EDC-crosslinked collagen (MR : 33-58 wt. %). Furthermore, FTIR, SEM and EDS revealed deposition of a calcium-phosphate phase on SBF-retrieved samples, whereby an increased calcium phosphate ratio (Ca/P: 0.84-1.41) was observed in hydrogels with higher Ph content. 72-hour material extracts were well tolerated by L929 mouse fibroblasts, whereby cell confluence and metabolic activity (MTS assay) were comparable to those of cells cultured in cell culture medium (positive control). In light of their controlled structure function properties, these biocompatible collagen hydrogels represent attractive material systems for potential mineralised tissue applications. PMID- 27390618 TI - Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and beta-adrenergic challenge are different. AB - BACKGROUND: Cardiac hypertrophy is the most potent cardiovascular risk factor after age, and relative mortality risk linked with cardiac hypertrophy is greater in women. Ischemic heart disease is the most common form of cardiovascular pathology for both men and women, yet significant differences in incidence and outcomes exist between the sexes. Cardiac hypertrophy and ischemia are frequently occurring dual pathologies. Whether the cellular (cardiomyocyte) mechanisms underlying myocardial damage differ in women and men remains to be determined. In this study, utilizing an in vitro experimental approach, our goal was to examine the proposition that responses of male/female cardiomyocytes to ischemic (and adrenergic) stress may be differentially modulated by the presence of pre existing cardiac hypertrophy. METHODS: We used a novel normotensive custom derived hypertrophic heart rat (HHR; vs control strain normal heart rat (NHR)). Cardiomyocyte morphologic and electromechanical functional studies were performed using microfluorimetric techniques involving simulated ischemia/reperfusion protocols. RESULTS: HHR females exhibited pronounced cardiac/cardiomyocyte enlargement, equivalent to males. Under basal conditions, a lower twitch amplitude in female myocytes was prominent in normal but not in hypertrophic myocytes. The cardiomyocyte Ca(2+) responses to beta-adrenergic challenge differed in hypertrophic male and female cardiomyocytes, with the accentuated response in males abrogated in females-even while contractile responses were similar. In simulated ischemia, a marked and selective elevation of end-ischemia Ca(2+) in normal female myocytes was completely suppressed in hypertrophic female myocytes-even though all groups demonstrated similar shifts in myocyte contractile performance. After 30 min of simulated reperfusion, the Ca(2+) desensitization characterizing the male response was distinctively absent in female cardiomyocytes. CONCLUSIONS: Our data demonstrate that cardiac hypertrophy produces dramatically different basal and stress-induced pathophenotypes in female- and male-origin cardiomyocytes. The lower Ca(2+) operational status characteristic of female (vs male) cardiomyocytes comprising normal hearts is not exhibited by myocytes of hypertrophic hearts. After ischemia/reperfusion, availability of activator Ca(2+) is suppressed in female hypertrophic myocytes, whereas sensitivity to Ca(2+) is blunted in male hypertrophic myocytes. These findings demonstrate that selective intervention strategies should be pursued to optimize post-ischemic electromechanical support for male and female hypertrophic hearts. PMID- 27390620 TI - Modelling levels of nitrous oxide exposure for healthcare professionals during EMONO usage. AB - BACKGROUND: Computational fluid dynamics (CFD) has been used to compute nitrous oxide (N2O) levels within a room during the administration of an equimolar mix of N2O/oxygen (EMONO) in the clinical setting. This study modelled realistic scenarios of EMONO usage in hospital or primary care, in order to estimate the potential N2O exposure of healthcare professionals (HCP) with routine EMONO use and to provide guidance for EMONO users. METHODS: Sixteen scenarios were defined by carrying out a survey of practitioners. CFD simulations were performed for each scenario and N2O concentrations over time were calculated. N2O exposures (time-weighted average of concentration over 8 h [TWA-8 h]) were calculated at the HCPs' mouth to be compared with a predefined occupational exposure limit (OEL). RESULTS: Administration duration and ventilation type were the main factors influencing N2O levels; ventilation type also influenced wash-out time between EMONO administrations. N2O concentration showed a plume distribution towards the ceiling and was highly heterogeneous, highlighting the importance of measurement location. Although estimated TWA-8 h varied widely, 13 of the 16 scenarios had an N2O TWA-8 h of <100 parts per million. CONCLUSIONS: Data demonstrate that EMONO usage in well ventilated rooms - as recommended - helps to ensure that N2O exposure does not exceed the OEL and does not signal any major risks for HCPs when recommendations are followed. Although these data are numerical simulations and should be considered as such, they can provide guidance for EMONO users. PMID- 27390621 TI - Knockdown of MLO genes reduces susceptibility to powdery mildew in grapevine. AB - Erysiphe necator is the causal agent of powdery mildew (PM), one of the most destructive diseases of grapevine. PM is controlled by sulfur-based and synthetic fungicides, which every year are dispersed into the environment. This is why PM resistant varieties should become a priority for sustainable grapevine and wine production. PM resistance can be achieved in other crops by knocking out susceptibility S-genes, such as those residing at genetic loci known as MLO (Mildew Locus O). All MLO S-genes of dicots belong to the phylogenetic clade V, including grapevine genes VvMLO7, 11 and 13, which are upregulated during PM infection, and VvMLO6, which is not upregulated. Before adopting a gene-editing approach to knockout candidate S-genes, the evidence that loss of function of MLO genes can reduce PM susceptibility is necessary. This paper reports the knockdown through RNA interference of VvMLO6, 7, 11 and 13. The knockdown of VvMLO6, 11 and 13 did not decrease PM severity, whereas the knockdown of VvMLO7 in combination with VvMLO6 and VvMLO11 reduced PM severity up to 77%. The knockdown of VvMLO7 and VvMLO6 seemed to be important for PM resistance, whereas a role for VvMLO11 does not seem likely. Cell wall appositions (papillae) were present in both resistant and susceptible lines in response to PM attack. Thirteen genes involved in defense were less upregulated in infected mlo plants, highlighting the early mlo-dependent disruption of PM invasion. PMID- 27390622 TI - Developmental origins of epigenetic transgenerational inheritance. AB - Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID- 27390623 TI - Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs. AB - Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin induced disease phenotypes. Data suggest potential connections between sperm borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon. PMID- 27390625 TI - Experimental Implementation of Underactuated Potential Energy Shaping on a Powered Ankle-Foot Orthosis. AB - Traditional control methodologies of rehabilitation orthoses/exoskeletons aim at replicating normal kinematics and thus fall into the category of kinematic control. This control paradigm depends on pre-defined reference trajectories, which can be difficult to adjust between different locomotor tasks and human subjects. An alternative control category, kinetic control, enforces kinetic goals (e.g., torques or energy) instead of kinematic trajectories, which could provide a flexible learning environment for the user while freeing up therapists to make corrections. We propose that the theory of underactuated potential energy shaping, which falls into the category of kinetic control, could be used to generate virtual body-weight support for stroke gait rehabilitation. After deriving the nonlinear control law and simulating it on a human-like biped model, we implemented this controller on a powered ankle-foot orthosis that was designed specifically for testing torque control strategies. Experimental results with an able-bodied human subject demonstrate the feasibility of the control approach for both positive and negative virtual body-weight augmentation. PMID- 27390626 TI - Advanced Analysis Techniques for Intra-cardiac Flow Evaluation from 4D Flow MRI. AB - PURPOSE OF THE REVIEW: Time-resolved 3D velocity-encoded MR imaging with velocity encoding in three directions (4D Flow) has emerged as a novel MR acquisition technique providing detailed information on flow in the cardiovascular system. In contrast to other clinically available imaging techniques such as echo-Doppler, 4D Flow MRI provides the 3D Flow velocity field within a volumetric region of interest over the cardiac cycle. This work reviews the most recent advances in the development and application of dedicated image analysis techniques for the assessment of intra-cardiac flow features from 4D Flow MRI. RECENT FINDINGS: Novel image analysis techniques have been developed for extraction of relevant intra-cardiac flow features from 4D Flow MRI, which have been successfully applied in various patient cohorts and volunteer studies. Disturbed flow patterns have been linked with valvular abnormalities and ventricular dysfunction. Recent technical advances have resulted in reduced scan times and improvements in image quality, increasing the potential clinical applicability of 4D Flow MRI. SUMMARY: 4D Flow MRI provides unique capabilities for 3D visualization and quantification of intra-cardiac blood flow. Contemporary knowledge on 4D Flow MRI shows promise for further exploration of the potential use of the technique in research and clinical applications. PMID- 27390624 TI - Forkhead transcription factors: new considerations for alzheimer's disease and dementia. AB - Life expectancy of individuals in both developed and undeveloped nations continues to rise at an unprecedented rate. Coupled to this increase in longevity for individuals is the rise in the incidence of chronic neurodegenerative disorders that includes Alzheimer's disease (AD). Currently, almost ten percent of the population over the age of 65 suffers from AD, a disorder that is presently without definitive therapy to prevent the onset or progression of cognitive loss. Yet, it is estimated that AD will continue to significantly increase throughout the world to impact millions of individuals and foster the escalation of healthcare costs. One potential target for the development of novel strategies against AD and other cognitive disorders involves the mammalian forkhead transcription factors of the O class (FoxOs). FoxOs are present in "cognitive centers" of the brain to include the hippocampus, the amygdala, and the nucleus accumbens and may be required for memory formation and consolidation. FoxOs play a critical role in determining survival of multiple cell types in the nervous system, drive pathways of apoptosis and autophagy, and control stem cell proliferation and differentiation. FoxOs also interface with multiple cellular pathways that include growth factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) that ultimately may control FoxOs and determine the fate and function of cells in the nervous system that control memory and cognition. Future work that can further elucidate the complex relationship FoxOs hold over cell fate and cognitive function could yield exciting prospects for the treatment of a number of neurodegenerative disorders including AD. PMID- 27390627 TI - The Unhappy Triad: Pain, Sleep Complaints, and Internalizing Symptoms. AB - There is limited understanding of the etiology and temporal relations of chronic pain, sleep complaints, and depression/anxiety. Several models have been proposed by which sleep disruption represents a common mechanism for the comorbidity of these symptoms. The goals of this study were to 1) clarify the boundaries of these domains and to 2) examine the relations of these symptoms over time following exposure to stressful and potentially traumatic experiences during a combat deployment. We found support for three distinct domains of sleep complaints, internalizing symptoms, and physical complaints. We tested two competing models that have been proposed in the literature, controlling for negative and positive emotionality. Internalizing symptoms strongly mediated the relation between sleep complaints and pain (total effect = .15, direct effect = .05). The study suggests that increases in sleep complaints immediately following deployment increase the risk of internalizing symptoms and pain several years after deployment. PMID- 27390628 TI - Good Clinical Practice Training: Identifying Key Elements and Strategies for Increasing Training Efficiency. AB - Good Clinical Practice (GCP) is an international standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials. The goal of GCP is to ensure the protection of the rights, integrity, and confidentiality of clinical trial participants and to ensure the credibility and accuracy of data and reported results. In the United States, trial sponsors generally require investigators to complete GCP training prior to participating in each clinical trial to foster GCP and as a method to meet regulatory expectations (ie, sponsor's responsibility to select qualified investigators per 21 CFR 312.50 and 312.53(a) for drugs and biologics and 21 CFR 812.40 and 812.43(a) for medical devices). This training requirement is often extended to investigative site staff, as deemed relevant by the sponsor, institution, or investigator. Those who participate in multiple clinical trials are often required by sponsors to complete repeated GCP training, which is unnecessarily burdensome. The Clinical Trials Transformation Initiative convened a multidisciplinary project team involving partners from academia, industry, other researchers and research staff, and government to develop recommendations for streamlining current GCP training practices. Recommendations drafted by the project team, including the minimum key training elements, frequency, format, and evidence of training completion, were presented to a broad group of experts to foster discussion of the current issues and to seek consensus on proposed solutions. PMID- 27390630 TI - Evaluation of the effects of school zone signs and markings on speed reduction: a driving simulator study. AB - Traffic control devices are one of the most significant factors affecting driving behavior. In China, there is a lack of installation guidelines or standards for traffic control devices in school zones. In addition, little research has been done to examine the effects of traffic control devices on driving behavior. Few guidelines have been established for implementing traffic control devices in school zones in China. This research conducted a driving simulator experiment to assess the effects of school zone signs and markings for two different types of schools. The efficiency of these traffic control devices was evaluated using four variables derived from the driving simulation, including average speed, relative speed difference, standard deviation of acceleration, and 85th percentile speed. Results showed that traffic control devices such as the Flashing Beacon and School Crossing Ahead Warning Assembly, the Reduce Speed and School Crossing Warning Assembly, and the School Crossing Ahead Pavement Markings were recommended for school zones adjacent to a major multilane roadway, which is characterized by a median strip, high traffic volume, high-speed traffic and the presence of pedestrian crossing signals. The School Crossing Ahead Pavement Markings were recommended for school zones on a minor two-lane roadway, which is characterized by low traffic volume, low speed, and no pedestrian crossing signals. PMID- 27390631 TI - Effects of aging on the structural, mechanical, and thermal properties of the silicone rubber current transformer insulation bushing for a 500 kV substation. AB - In order to analyze the cracking and aging reason of the silicone rubber current transformer (CT) insulation bushing used for 8 years from a 500 kV alternating current substation, characteristics including Fourier transform infrared (FTIR) spectroscopy, mechanical properties analysis, hardness, and thermo gravimetric analysis have been carried out. The FTIR results indicated that the external surface of the silicone rubber CT insulation bushing suffered from more serious aging than the internal part, fracture of side chain Si-C bond was much more than the backbone. Mechanical properties and thermal stability results illustrated that the main aging reasons were the breakage of side chain Si-C bond and the excessive cross-linking reaction of the backbone. This study can provide valuable basis for evaluating degradation mechanism and aging state of the silicone rubber insulation bushing in electric power field. PMID- 27390629 TI - Platelet generation in vivo and in vitro. AB - Platelet (PLT) transfusion, which is the primary cell therapy for thrombocytopenia, has been a source of concern in recent years due to its limitations of donor-dependent supply and soaring costs. In vitro platelet generation on an industrial scale is a possible solution requiring exploration. The technology of platelet generation ex vivo has been widely studied across the world, though the mechanisms of physiological thrombopoiesis and platelet biology function in vivo still remain elusive today. Various culture systems have been studied, most of which proved quite inefficient in generating functional platelets ex vivo, so there is still a long way to reach our ultimate goal of generating a fully functional platelet in vitro on an industrial scale. This review integrates the latest research into physiological platelet biogenesis and ex vivo-platelet/megakaryocyte (MK) generation protocols with a focus on the ability to generate PLT/MK in large quantities, summarizes current culture systems based on induced human pluripotent stem cells and adipose-derived stem cells, and discusses significant challenges that must be overcome for these approaches to be perfected. PMID- 27390632 TI - Identification and evaluation of reference genes in the Chinese white wax scale insect Ericerus pela. AB - BACKGROUND: The Chinese white wax scale insect, Ericerus pela, is a well-known resource insect. The females and males are dramatically distinct at each developmental stage. We sought to identify suitable reference genes to use as internal controls in molecular research on E. plea. RESULTS: geNorm, RefFinder and Normfinder analyses showed that betaTub-2 was the best reference gene throughout different developmental stages; SdhA-1 was the most stable reference gene in different tissues, and betaTub-1 was the most reliable reference gene under treatment with different temperatures. The results also showed that the optimal number of reference genes for analyzing target gene expression levels in the three experimental conditions was two. CONCLUSIONS: The identified reference genes are suitable reference genes for normalization in RT-qPCR of E. pela samples. PMID- 27390633 TI - Forest adjacent households' voices on their perceptions and adaptation strategies to climate change in Kilombero District, Tanzania. AB - Climate change is a global and local challenge to both sustainable livelihoods and economic development. Tanzania as other countries of the world has been affected. Several studies have been conducted on farmers' perceptions and adaptation to climate change in the country, but little attention has been devoted to forest adjacent households in humid areas. This study assessed this gap through assessing forest adjacent households' voices on perceptions and adaptation strategies to climate change in Kilombero District, Tanzania. Data collection involved key informant interviews, focus group discussions and household questionnaires. Results showed that the majority of households perceived changed climate in terms of temperature increase, unpredictable rainfall, frequent occurrence of floods, increased dry spells during rainy season coupled with decreased water sources and emergence of new pests and diseases. The perceived change in climate has impacted agriculture productivity as the main livelihood source. Different coping and adaptation strategies are employed. These are; crop diversification, changing cropping calendar, adopting modern farming technologies, and increasing reliance on non-timber forest products. These strategies were positively and significantly influenced by socio-economic factors including household size, residence period, land ownership and household income. The study concludes that, there are changes in climatic conditions; and to respond to these climatic changes, forest adjacent households have developed numerous coping and adaptation strategies, which were positively and significantly influenced by some socio-economic factors. The study calls for actual implementation of local climate change policies and strategies in order to enhance adaptive capacity at household level. PMID- 27390634 TI - Short and long-term effects of exergaming for the elderly. AB - OBJECTIVE: Exergaming has been introduced in safe and beneficial intervention for the elderly. However, no study has examined exergaming-based interventions for the elderly that last several years. Therefore, we investigated the effectiveness and safety of a 12-week intervention using step training with exergaming for the elderly (12-week study). Moreover, we conducted an exergaming-based intervention for 3 years (3-year study). MATERIALS AND METHODS: 12-week study: Forty-two elderly persons participated in this study. Using an in-house developed exergaming protocol, a step training was performed for 15 min/session twice a week for 12 weeks. We investigated post-intervention changes in motor functions, successful step-rate, the intensity of exercise, which was evaluated using Borg scale (Rating of Perceived Exertion). 3-year study: An intervention using exergaming was conducted for 12 weeks by 20 elderly participants. Two courses/year of exercise were performed at 3-month intervals. This was continued for 3 years. The exercise continuation rate, its influence on motor functions were investigated. RESULTS: 12-week study: Lower-limb muscle strength, balancing capacity, and whole body reaction time significantly improved in the exercise group. The mean score on Borg scale was 12 +/- 2 on the first day of the step exercise and 9 +/- 2 on the final day. 3-year study: Exercise was continued in 16 out of the 20 subjects. The Timed Up and Go Test, duration of one-footed standing, and quadriceps strength significantly improved. CONCLUSION: The results of the present study showed that exergaming provided an appropriate exercise intensity for the elderly and safely improved motor functions. The exercise continuation rate in the 3-year study was high. Improvements in motor functions may contribute to the prevention of falls. PMID- 27390636 TI - POD analysis of flow over a backward-facing step forced by right-angle-shaped plasma actuator. AB - PURPOSE: This study aims to present flow control over the backward-facing step with specially designed right-angle-shaped plasma actuator and analyzed the influence of various scales of flow structures on the Reynolds stress through snapshot proper orthogonal decomposition (POD). METHODS: 2D particle image velocimetry measurements were conducted on region (x/h = 0-2.25) and reattachment zone in the x-y plane over the backward-facing step at a Reynolds number of Re h = 27,766 (based on step height [Formula: see text] and free stream velocity [Formula: see text]. The separated shear layer was excited by specially designed right-angle-shaped plasma actuator under the normalized excitation frequency St h ~ 0.345 along the 45 degrees direction. The spatial distribution of each Reynolds stress component was reconstructed using an increasing number of POD modes. RESULTS: The POD analysis indicated that the flow dynamic downstream of the step was dominated by large-scale flow structures, which contributed to streamwise Reynolds stress and Reynolds shear stress. The intense Reynolds stress localized to a narrow strip within the shear layer was mainly affected by small scale flow structures, which were responsible for the recovery of the Reynolds stress peak. With plasma excitation, a significant increase was obtained in the vertical Reynolds stress peak. CONCLUSIONS: Under the dimensionless frequencies St h ~ 0.345 and [Formula: see text] which are based on the step height and momentum thickness, the effectiveness of the flow control forced by the plasma actuator along the 45 degrees direction was ordinary. Only the vertical Reynolds stress was significantly affected. PMID- 27390635 TI - Parametric investigation on mixing in a micromixer with two-layer crossing channels. AB - This work presents a parametric investigation on flow and mixing in a chaotic micromixer consisting of two-layer crossing channels proposed by Xia et al. (Lab Chip 5: 748-755, 2005). The flow and mixing performance were numerically analyzed using commercially available software ANSYS CFX-15.0, which solves the Navier Stokes and mass conservation equations with a diffusion-convection model in a Reynolds number range from 0.2 to 40. A mixing index based on the variance of the mass fraction of the mixture was employed to evaluate the mixing performance of the micromixer. The flow structure in the channel was also investigated to identify the relationship with mixing performance. The mixing performance and pressure-drop were evaluated with two dimensionless geometric parameters, i.e., ratios of the sub-channel width to the main channel width and the channels depth to the main channel width. The results revealed that the mixing index at the exit of the micromixer increases with increase in the channel depth-to-width ratio, but decreases with increase in the sub-channel width to main channel width ratio. And, it was found that the mixing index could be increased up to 0.90 with variations of the geometric parameters at Re = 0.2, and the pressure drop was very sensitive to the geometric parameters. PMID- 27390637 TI - Fruit physical characteristics, proximate, mineral and starch characterization of FHIA 19 and FHIA 20 plantain and FHIA 03 cooking banana hybrids. AB - Cooking banana and plantain (Musa spp. AAB and ABB groups), have over the years been affected by pest and diseases, resulting in various organizations developing disease resistant hybrids with superior agronomic potential. The characteristics of these improved varieties needs to be studied to ascertain their suitability for use in various food systems. This study aimed at evaluating the physical characteristics, proximate and minerals composition, and characterizing the starch of plantain and a cooking banana hybrid release by Fundacion Hondurena de Investigacion Agricola (FHIA), and comparing them to a local landrace in Ghana. FHIA 19 and FHIA 20 plantain, Apentu pa (a local landrace) and FHIA 03 cooking banana hybrid were used for the study. Their physical characteristics, proximate and mineral composition were determined at the proximal, midsection and distal hand positions. Starch granules and cells were then examined under light microscope. Ranges obtained for protein content for FHIA 20, FHIA 03 and FHIA 19 were 3.01-3.40, 2.66-2.91 and 2.81-2.91 %. Potassium was found to be the most abundant mineral in all the cultivars. The highest mean value of 982.5-1013.76 mg/100 g was obtained for FHIA 19. There were significant differences (p < 0.05) in the proximate and mineral composition of the varieties, however no significant difference exited between the hand positions. The largest starch granule size was found in FHIA 19 hybrid. FHIA 03 was also composed predominantly of two types: longitudinal and rounded granules with each type grouped together. The new plantain hybrids compared very well with the local landrace hence making them suitable to be incorporated into local food systems. PMID- 27390638 TI - Enhanced genetic algorithm optimization model for a single reservoir operation based on hydropower generation: case study of Mosul reservoir, northern Iraq. AB - Achievement of the optimal hydropower generation from operation of water reservoirs, is a complex problems. The purpose of this study was to formulate and improve an approach of a genetic algorithm optimization model (GAOM) in order to increase the maximization of annual hydropower generation for a single reservoir. For this purpose, two simulation algorithms were drafted and applied independently in that GAOM during 20 scenarios (years) for operation of Mosul reservoir, northern Iraq. The first algorithm was based on the traditional simulation of reservoir operation, whilst the second algorithm (Salg) enhanced the GAOM by changing the population values of GA through a new simulation process of reservoir operation. The performances of these two algorithms were evaluated through the comparison of their optimal values of annual hydropower generation during the 20 scenarios of operating. The GAOM achieved an increase in hydropower generation in 17 scenarios using these two algorithms, with the Salg being superior in all scenarios. All of these were done prior adding the evaporation (Ev) and precipitation (Pr) to the water balance equation. Next, the GAOM using the Salg was applied by taking into consideration the volumes of these two parameters. In this case, the optimal values obtained from the GAOM were compared, firstly with their counterpart that found using the same algorithm without taking into consideration of Ev and Pr, secondly with the observed values. The first comparison showed that the optimal values obtained in this case decreased in all scenarios, whilst maintaining the good results compared with the observed in the second comparison. The results proved the effectiveness of the Salg in increasing the hydropower generation through the enhanced approach of the GAOM. In addition, the results indicated to the importance of taking into account the Ev and Pr in the modelling of reservoirs operation. PMID- 27390639 TI - The behavioral response of Lasioderma serricorne (Coleoptera: Anobiidae) to citronellal, citral, and rutin. AB - The behavioral response of Lasioderma serricorne adults to citronellal, citral, and rutin was investigated by using the area preference method. The L. serricorne adults were exposed to citronellal, and citral at the rate of 1:10, 1:50, 1:100 and 1:1000 (citronellal: ethanol, v/v) for 1, 2, 12 and 24 h, to rutin at the rate of 10, 30 and 90 g/m(2) for 1, 2, 12 and 24 h, respectively. The citronellal and citral had attractive activity at the low rates and repellent potential at the high rates. The highest behavioral response values of L. serricorne adults to citronellal and citral were -88.89 % at the rate of 1:100 and 100.00 % at the rate of 1:50 respectively. Rutin had strong repellent effectiveness on L. serricorne adults, which significantly increased with increasing rates with the highest behavioral response values 100.00 % at the rate of 90 g/m(2) after 12 h exposure. These data suggest that the citronellal, citral, and rutin have great potential for preventing stored products from L. serricorne infestation. PMID- 27390641 TI - A conciliation mechanism for self-organizing dynamic small groups. AB - A group of individuals, organizations or things in internet of things (IoT) often dynamically self-organizes in small groups to accomplish certain tasks. This is common in virtual organization, social networks and the evolving field of IoT. These small groups have different behavioral characteristics than large groups. Members individually have some requirements and contribute some resources to the group. The organization and operation of such a group requires dynamic identification of group requirements that can be fulfilled by available resources and is approved by the group. We apply design science methods to develop an artifact that helps in conciliation of collective requirements and resources of small groups while maintaining each member's satisfaction. The mechanism also supports dynamic conciliation as members leave and new members join the group. Each member's requirement is specified as an explicit/implicit objective that is feasible/not feasible based on resources available to the group and whether the requirement is in alignment with other members' objectives. We validate the artifact by using it for a manufacturing service group and simulating the change in collective group requirements and resources as group membership changes dynamically. PMID- 27390640 TI - High thoracic anesthesia offers no major benefit over general anesthesia in on pump cardiac surgery patients: a retrospective study. AB - BACKGROUND: Thoracic epidural anesthesia (TEA) has been proposed to improve and facilitate early postoperative outcome in cardiac surgery. The aim of our study was to analyze early postoperative outcome data of patients undergoing cardiac surgery under general anesthesia (GA) with comparison to patients receiving combined TEA and GA. METHODS: Medical records data from 288 patients who underwent elective on-pump cardiac surgery were retrieved and analyzed. Patients were divided into two study groups according to the type of anesthesia used: GA group (n = 141) and TEA group (n = 147). Early postoperative outcome data including quality of analgesia and major organ outcome parameters were compared between the study groups. RESULTS: There was no major difference in early postoperative outcome data between the study groups, except for shorter time to extubation (6.0 +/- 10.0 vs. 6.9 +/- 8.8 h, respectively, P < 0.05) and hospital stay (10.7 +/- 5.9 vs. 12.9 +/- 8.8 days, respectively, P < 0.05) in TEA group compared to GA group. Also TEA group as compared to GA group had lower pain numeric rating scale scores (1 +/- 1.1 vs. 1.4 +/- 1.5 at 24 h, respectively, P < 0.05) and morphine requirements during the first 24 h after surgery (148.2 vs. 193 +/- 85.4 MUg/kg, respectively, P < 0.05). CONCLUSION: Both anesthetic methods were equivalent in most postoperative outcome measures. Thoracic epidural analgesia provided superior pain relief, shorter time to extubation and earlier hospital discharge. PMID- 27390643 TI - C-class functions with new approach on coincidence point results for generalized [Formula: see text]-weakly contractions in ordered b-metric spaces. AB - In this paper, by using the C-class functions and a new approach we present some coincidence point results for four mappings satisfying generalized [Formula: see text]-weakly contractive condition in the setting of ordered b-metric spaces. Also, an application and example are given to support our results. PMID- 27390642 TI - Therapeutic hypothermia versus normothermia in adult patients with traumatic brain injury: a meta-analysis. AB - INTRODUCTION: Many single-center studies and meta-analyses demonstrate that therapeutic hypothermia (TH), in which the body temperature is maintained at 32 35 degrees C, exerts significant neuroprotection and attenuates secondary intracranial hypertension after traumatic brain injury (TBI). In 2015, two well designed multi-center, randomized controlled trials were published that did not show favorable outcomes with the use of TH in adult patients with TBI compared to normothermia treatment (NT). Therefore, we performed an updated meta-analysis to assess the effect of TH in adult patients with TBI. METHODS: We reviewed the PubMed, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Databases. We included randomized controlled trials that compared TH and NT in adult patients with TBI. Two reviewers assessed the quality of each study and independently collected the data. We performed the meta-analysis using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: We included 18 trials involving 2177 patients with TBI. There was no significant heterogeneity among the studies. TH could not decrease mortality at 3 months post-TBI (RR 0.95; 95 % CI 0.59, 1.55; z = 0.19, P = 0.85) or 6 months post-TBI (RR 0.96; 95 % CI 0.76, 1.23; z = 0.29, P = 0.77). There were no significant differences in unfavorable clinical outcomes when TH was compared to NT at 3 months post-TBI (RR 0.79; 95 % CI 0.56, 1.12; z = 1.31, P = 0.19) or 6 months post-TBI (RR 0.80; 95 % CI 0.63, 1.00; z = 1.92, P = 0.05). TH was associated with a significant increase in pneumonia (RR 1.51; 95 % CI 1.12, 2.03; z = 2.72, P = 0.006) and cardiovascular complications (RR 1.75; 95% CI 1.14, 2.70; z = 2.54, P = 0.01). CONCLUSIONS: Therapeutic hypothermia failed to demonstrate a decrease in mortality and unfavorable clinical outcomes at 3 or 6 months post-TBI. Additionally, TH might increase the risk of developing pneumonia and cardiovascular complications. PMID- 27390644 TI - Hybrid algorithm for common solution of monotone inclusion problem and fixed point problem and applications to variational inequalities. AB - The aim of this paper is to investigate hybrid algorithm for a common zero point of the sum of two monotone operators which is also a fixed point of a family of countable quasi-nonexpansive mappings. We point out two incorrect proof in paper (Hecai in Fixed Point Theory Appl 2013:11, 2013). Further, we modify and generalize the results of Hecai's paper, in which only a quasi-nonexpansive mapping was considered. In addition, two family of countable quasi-nonexpansive mappings with uniform closeness examples are provided to demonstrate our results. Finally, the results are applied to variational inequalities. PMID- 27390645 TI - IgG4-related disease: a case report with duration of more than 16 years and review of literature. AB - INTRODUCTION: IgG4-related disease was first reported in 2001 and was officially named in 2010. It is now considered as a systemic disease that might affect any organ system. The characteristic pathological changes of IgG4-related disease are extensive infiltration of IgG4-positive plasma cells. IgG4-related disease is a kind of benign lesions, but there has not been well-defined standard treatment so far. Patients usually respond well to corticosteroids. The prognosis of IgG4 related disease is perhaps good as long as early detection and treatment. CASE DESCRIPTION: We report one case of IgG4-related disease with a 16-years anamnesis with multi-pseudotumor masses. He was diagnosed with chronic kidney disease with wide interstitial renal fibrosis. And he received glucocorticoids therapy. After 2 month therapy, the serum creatinine, erythrocyte sedimentation rate, and serum IgG4 decreased significantly. The discussion includes presentation, clinical course, diagnosis, and prognosis of IgG4-related disease. The case and discussion highlight the importance of diagnosis and the good prognosis of IgG4-related diseases. DISCUSSION AND EVALUATION: Our case highlights the importance of diagnosis and the good prognosis of IgG4-related diseases. IgG4-related disease is a systemic fibro-inflammatory immune-mediated disorder and now recognized in almost every major organs. Characteristics of the disease is multiple lymph nodes and the response to glucocorticoids therapy is well. In such case, he had a history of 16 years with multi-pseudotumor masses and misdiagnosed for 16 years, if the doctors were not awareness of higher serum immunoglobulin G4 (IgG4) than normal, the correct diagnosis may be missed or delayed. Consequently, appropriate treatment for IgG4-related disease would also be delayed or not provided and likely result in increased morbidity and mortality. CONCLUSIONS: IgG4-related disease is a systemic fibro-inflammatory immune-mediated disorder and progresses slowly. In the present patient the course of IgG4-related disease appears to be benign. The prognosis of IgG4-related disease depend on early diagnosis and treatment. PMID- 27390647 TI - Drying kinetics and mathematical modeling of hot air drying of coconut coir pith. AB - Drying kinetics of coir pith was studied and the properties of compressed coir pith discs were analyzed. Coir pith particles were oven dried in the range of temperatures from 100 to 240 degrees C and the rehydration ability of compressed coir pith was evaluated by finding the volume expansion. The optimum drying temperature was found to be 140 degrees C. Hot air drying was carried out to examine the drying kinetics by allowing the coir pith particles to fluidize and circulate inside the drying chamber. Particle motion within the drying chamber closely resembled the particle motion in a flash dryer. The effective moisture diffusivity was found to increase from 1.18 * 10(-8) to 1.37 * 10(-8) m(2)/s with the increase of air velocity from 1.4 to 2.5 m/s respectively. Correlation analysis and residual plots were used to determine the adequacy of existing mathematical models for describing the drying behavior of coir pith. The empirical models, Wang and Singh model and Linear model, were found to be adequate for accurate prediction of drying behavior of coir pith. A new model was proposed by modifying the Wang and Singh model and considering the effect of air velocity. It gave the best correlation between observed and predicted moisture ratio with high value of coefficient of determination (R(2)) and lower values of root mean square error, reduced Chi square (chi(2)) and mean relative deviation (E%). PMID- 27390646 TI - PD-L1 expression and CD274 gene alteration in triple-negative breast cancer: implication for prognostic biomarker. AB - PURPOSE: To estimate the therapeutic potential of PD-L1 inhibition in breast cancer, we evaluated the prevalence and significance of PD-L1 protein expression with a validated antibody and CD274 gene alternation in a large cohort of triple negative breast cancer (TNBC) and correlated with clinicopathological data and patients overall survival. METHODS: Immunohistochemistry and in situ mRNA hybridization was used to detect PD-L1 protein and mRNA expression in tumor tissues from 183 TNBC patients respectively. Fluorescence in situ hybridization analysis was performed on PD-L1 strong expression samples to assess copy number on chromosome 9p24.1 of CD274 gene. RESULTS: Expression of PD-L1 by immune cells was observed in 4.9 % of TNBC, while expression by tumor cells accounted for 8.7 %. There was a high concordance in PD-L1 protein expression and PDL1 mRNA expression. Samples with PD-L1 strong expression were found to have a CD274 gene copy number gain. PD-L1 expression was correlated with higher tumor grade, but was independent of menopausal status, lymph nodes metastasis, histological subtype and tumor size. In addition, we used precise stratification of PD-L1 expression on tumor or immune cells of certain breast cancer subtype and suggested that patients with PD-L1 expression in basal-like tumors by immune cells or with CD274 gene copy number gain had a longer disease-specific overall survival. CONCLUSIONS: Our findings may promote the more precise analysis of PD L1 expression in breast cancer and aid the selection of patients who may benefit from immune therapy. PMID- 27390649 TI - Complexity of line-seru conversion for different scheduling rules and two improved exact algorithms for the multi-objective optimization. AB - Productivity can be greatly improved by converting the traditional assembly line to a seru system, especially in the business environment with short product life cycles, uncertain product types and fluctuating production volumes. Line-seru conversion includes two decision processes, i.e., seru formation and seru load. For simplicity, however, previous studies focus on the seru formation with a given scheduling rule in seru load. We select ten scheduling rules usually used in seru load to investigate the influence of different scheduling rules on the performance of line-seru conversion. Moreover, we clarify the complexities of line-seru conversion for ten different scheduling rules from the theoretical perspective. In addition, multi-objective decisions are often used in line-seru conversion. To obtain Pareto-optimal solutions of multi-objective line-seru conversion, we develop two improved exact algorithms based on reducing time complexity and space complexity respectively. Compared with the enumeration based on non-dominated sorting to solve multi-objective problem, the two improved exact algorithms saves computation time greatly. Several numerical simulation experiments are performed to show the performance improvement brought by the two proposed exact algorithms. PMID- 27390648 TI - Global comparison of phosphoproteins in human and rodent hearts: implications for translational studies of myosin light chain and troponin phosphorylations. AB - Cardiac remodeling and failure are regulated by a myriad of cardiac protein phosphorylations. In the present study, cardiac phosphoprotein patterns were examined in rodent and human hearts Left ventricular tissue samples were obtained from human systolic failing (n = 5) and control (n = 5) hearts and from two rat models of hypertensive heart failure, i.e., spontaneously hypertensive heart failure and Dahl salt-sensitive rats and corresponding controls. Phosphoproteins were separated by 2D-DIGE with Cydye staining, phosphoprotein patterns were analyzed using pixel intensity in rectified images. Specific phosphoproteins which were different in human versus rodent hearts were identified by MALDI TOF/TOF Mass Spectrometry. Targeted pair-wise analyses showed differences (p < 0.05) in 26 % of the pixels, which included pixels containing phosphorylated troponin T, myosin light chain, peroxiredoxin, and haptoglobin. These results show differences in rodent versus human cardiac remodeling which will influence the translation rodent studies to humans in this area. PMID- 27390650 TI - Meal context and food preferences in cancer patients: results from a French self report survey. AB - PURPOSE: The present study examined patient self-reports of descriptions, experiences and consequences of meal disturbances and food preferences within a cultural context (i.e., French meal traditions) in various treated cancer patients along their disease trajectory. METHODS: Over 800 questionnaires were sent to 20 cancer treatment centres in France. During a 9-month period, 255 questionnaires were received from five centres. Inclusion criteria included those French patients over 18 years of age, could read and understand French, had an Eastern Cooperative Oncology Group score between 0 and 2, experienced treatment induced nutrition changes and/or had decreased oral intake. Dietetic staff assessed clinical characteristics while patients completed a 17-item questionnaire. RESULTS: The majority of patients were diagnosed with breast, gastro-intestinal (GI) tract and head and neck cancers (62 %). Half of the patients (49 %) experienced weight loss >5 %. The main treatment-induced side effects were fatigue, nausea, dry mouth, hypersensitivity to odors and GI tract transit disorders. These discomforts affected eating and drinking in 83 % of patients, inducing appetite loss and selected food aversion. Food preference appeared heterogeneous. Food taste, odor and finally appearance stimulated appetite. Finally, dietary behaviors and satisfaction were driven by the extent to which food was enjoyed. CONCLUSIONS: During oncologic treatments, eating and drinking were affected in more than three-quarters of patients. As recommended by practice guidelines, nutritional assessment and follow-up are required. Personalized nutritional counseling should include the role of the family, patient's meal traditions, and food habits. PMID- 27390652 TI - Dynamics of land use and land cover change (LULCC) using geospatial techniques: a case study of Islamabad Pakistan. AB - One of the detailed and useful ways to develop land use classification maps is use of geospatial techniques such as remote sensing and Geographic Information System (GIS). It vastly improves the selection of areas designated as agricultural, industrial and/or urban sector of a region. In Islamabad city and its surroundings, change in land use has been observed and new developments (agriculture, commercial, industrial and urban) are emerging every day. Thus, the rationale of this study was to evaluate land use/cover changes in Islamabad from 1992 to 2012. Quantification of spatial and temporal dynamics of land use/cover changes was accomplished by using two satellite images, and classifying them via supervised classification algorithm and finally applying post-classification change detection technique in GIS. The increase was observed in agricultural area, built-up area and water body from 1992 to 2012. On the other hand forest and barren area followed a declining trend. The driving force behind this change was economic development, climate change and population growth. Rapid urbanization and deforestation resulted in a wide range of environmental impacts, including degraded habitat quality. PMID- 27390651 TI - A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene. AB - Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to comprehensively and systematically analyze the SNPs of MBL2 gene. The present study was carried out to identify and prioritize the SNPs of MBL2 gene for further genotyping and functional studies. To predict the possible impact of SNPs on MBL structure and function SNP data obtained from dbSNP database were analyzed using various bioinformatics tools. Out of total 661 SNPs, only 37 validated SNPs having minor allele frequency >=0.10 were considered for the present study. These 37 SNPs includes one in 3' near gene, nine in 3' UTR, one non-synonymous SNP (nsSNP), thirteen intronic SNPs and thirteen in 5' near gene. From these 37 SNPs, 11 non coding SNPs were identified to be of functional significance and evolutionary conserved. Out of these, 4 SNPs from 3' UTR were found to play role in miRNA binding, 7 SNPs from 5' near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. Protein structural analysis with this amino acid variant was performed by using I-TASSER, RAMPAGE, Swiss-PdbViewer, Chimera and I-mutant. Information regarding solvent accessibility, molecular dynamics and energy minimization calculations showed that this variant causes clashes with neighboring amino acids residues that must interfere in the normal triple helix formation of trimeric subunit and further with the normal assembly of MBL oligomeric form, hence decrease in stability. Thus, findings of the present study indicated 12 SNPs of MBL2 gene to be functionally important. Exploration of these variants may provide novel remedial markers for various diseases. PMID- 27390653 TI - Closed-form solution for a cantilevered sectorial plate subjected to a tip concentrated force. AB - A closed-form solution is presented for a cantilevered sectorial plate subjected to a tip concentrated force. Since the particular solution for this problem was not found in the literature, it is derived here. Deflections from the total solution (particular plus homogeneous solutions) are compared to those from a finite element analysis and are found to be in excellent agreement, producing an error within approximately 0.08 %. Normalized closed-form deflections and slopes at the fixed support, resulting from an approximate enforcement of the boundary conditions there, deviate from zero by <0.08 %. Finally, the total closed-form solutions for a cantilevered sectorial plate subjected to independent applications of a tip concentrated force, a tip bending moment, and a tip twisting moment, are compiled. PMID- 27390654 TI - Comparison of CRISPR/Cas9 and TALENs on editing an integrated EGFP gene in the genome of HEK293FT cells. AB - BACKGROUND: Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome. To date few comparative studies have been carried out to investigate the difference of genome editing characteristics between CRISPR/Cas9 and TALENs. While the CRISPR/Cas9 system has overtaken TALENs as the tool of choice for most research groups working in this field, we hypothesized that there could be certain applications whereby the application of TALENs would have specific benefits. Here we compare CRISPR/Cas9 and TALEN as tools for introducing site-specific editing events at an integrated EGFP gene in the genome of HEK293FT cells. RESULTS: Guide RNAs and TALEN pairs were designed to target two loci within the EGFP gene. We found that paired Cas9 nucleases induced targeted genomic deletion more efficiently and precisely than two TALEN pairs. However, when concurrently supplied with a plasmid template spanning the two DNA double-strand breaks (DSBs) within EGFP, TALENs stimulated homology directed repair (HDR) more efficiently than CRISPR/Cas9 and caused fewer targeted genomic deletions. CONCLUSIONS: Our data suggest that the choice of genome editing tool should be determined by the desired genome editing outcome. Such a rational approach is likely to benefit research outputs for groups working in fields as diverse as modification of cell lines, to animal models for disease studies, or gene therapy strategies. PMID- 27390655 TI - Orally administered beta-glucan attenuates the Th2 response in a model of airway hypersensitivity. AB - beta-Glucan is a polysaccharide that can be extracted from fungal cell walls. Wellmune WGP((r)), a preparation of beta-1,3/1,6-glucans, is a dietary supplement that has immunomodulating properties. Here we investigated the effect WGP had on a mouse model of asthma. OVA-induced asthma in mice is characterized by infiltration of eosinophils into the lung, production of Th2 cytokines and IgE. Daily oral administration of WGP (400 ug) significantly reduced the influx of eosinophils into the lungs of OVA-challenged mice compared to control mice. In addition, WGP inhibited pulmonary production of Th2 cytokines (IL-4, IL-5, IL 13), however serum IgE levels were unaffected by WGP treatment. These data indicate that WGP could potentially be useful as an oral supplement for some asthma patients, however, it would need to be combined with therapies that target other aspects of the disease such as IgE levels. As such, further studies that examine the potential of WGP in combination with other therapies should be explored. PMID- 27390656 TI - Dietary supplementation with shiikuwasha extract attenuates dexamethasone-induced skeletal muscle atrophy in aged rats. AB - BACKGROUND: Skeletal muscle atrophy is caused by a variety of diseases and conditions. In particular, skeletal muscle atrophy in the elderly contributes to a loss of independence with advanced age and increases the risk of falling. However, the effect of food consumed on a daily basis on skeletal muscle atrophy has been the focus of little research. In this study, the effects of dietary supplementation with shiikuwasha extract or grape extract on dexamethasone induced skeletal muscle atrophy were evaluated in aged rats. METHODS: Aged male rats (15-month-old) were fed a diet supplemented with either 1 % shiikuwasha extract or 1 % grape extract for 19 days. During the last 5 days of the feeding period, rats were injected with dexamethasone to induce muscle atrophy. RESULTS: Body weight and hind-limb muscle weight were significantly decreased by dexamethasone treatment. The supplementation of shiikuwasha extract showed no effect on body weight loss, but markedly attenuated tibialis anterior muscle weight loss induced by dexamethasone. On the other hand, grape extract did not affect muscle weight loss. Furthermore, shiikuwasha extract significantly reduced dexamethasone-induced expression of atrogin-1 and MuRF1 mRNA, but did not reduce LC3B-II protein levels. CONCLUSION: These results suggest that shiikuwasha extract may partially inhibit the activation of the ubiquitin-proteasome system and may consequently attenuate skeletal muscle atrophy induced by dexamethasone in aged rats. PMID- 27390657 TI - Single- and two-phase flow simulation based on equivalent pore network extracted from micro-CT images of sandstone core. AB - Due to the intricate structure of porous rocks, relationships between porosity or saturation and petrophysical transport properties classically used for reservoir evaluation and recovery strategies are either very complex or nonexistent. Thus, the pore network model extracted from the natural porous media is emphasized as a breakthrough to predict the fluid transport properties in the complex micro pore structure. This paper presents a modified method of extracting the equivalent pore network model from the three-dimensional micro computed tomography images based on the maximum ball algorithm. The partition of pore and throat are improved to avoid tremendous memory usage when extracting the equivalent pore network model. The porosity calculated by the extracted pore network model agrees well with the original sandstone sample. Instead of the Poiseuille's law used in the original work, the Lattice-Boltzmann method is employed to simulate the single- and two- phase flow in the extracted pore network. Good agreements are acquired on relative permeability saturation curves of the simulation against the experiment results. PMID- 27390658 TI - Enzymatic characterization of two acetyl-CoA synthetase genes from Populus trichocarpa. AB - The acetyl-CoA synthetase (ACS) family is a subfamily of adenylate-forming enzymes, which has a close evolutionary relationship with the 4-coumarate:CoA ligase (4CL) family. In this study, two ACS genes were cloned from Populus trichocarpa and were named PtrACS1 and PtrACS2. Bioinformatics characterization of PtrACS1 and PtrACS2 showed that they contained the key ACS residues and a putative peroxisome targeting sequence 1 (PTS1) at the end of the C-terminal sequence. Real-time PCR results showed that PtrACS1 and PtrACS2 were expressed in the phloem, xylem, leaves, and roots of one-year-old P. trichocarpa, but were expressed primarily in the leaves. The ACS enzyme activity was higher in leaves than other tissues in P. trichocarpa. Two overexpressed recombinant proteins showed no catalytic activity toward the substrates of 4CL, but did have notable catalytic activity toward sodium acetate and substrates of ACS. The relative activities of PtrACS1 and PtrACS2 were 194.16 +/- 11.23 and 422.25 +/- 21.69 MUM min(-1) mg(-1), respectively. The K m and V max of PtrACS1 were 0.25 mM and 698.85 MUM min(-1) mg(-1), while those for PtrACS2 were 0.72 mM and 245.96 MUM min(-1) mg(-1), respectively. Our results revealed that both proteins belong to the ACS family, and provide a theoretical foundation for the identification and functional analysis of members of the adenylate-forming enzyme superfamily. PMID- 27390660 TI - Evaluation of actual and estimated hydraulic conductivity of sands with different gradation and shape. AB - Hydraulic conductivities of sands with different gradation and grain shape were estimated experimentally at a relative density (Dr) of about 40 % and a 22 +/- 2 degrees C of constant temperature. Narli Sand (NS) with 0.67 of sphericity (S) and 0.72 of roundness (R), and Crushed Stone Sand (CSS) with 0.55 of S and 0.15 of R values were artificially graded into sixteen different grain-size fractions (4.75-2, 2-1.18, 1.18-0.6, 0.6-0.425, 0.425-0.3, 0.3-0.075, 4.75-0.075, 2-0.075, 1.18-0.075, 0.6-0.075, 0.425-0.075, 4.75-0.6, 2-0.6, 4.75-0.425, 2-0.425, 1.18 0.425 mm). Hydraulic conductivities of the NS estimated by use of constant head test ranged from 1.61 to 0.01 cm/s, whilst those of the CSS estimated by the same test ranged from 2.45 to 0.012 cm/s. It was observed that the hydraulic conductivity values of the NS are lower than those of the CSS samples, which is likely to be the result of differences in shape, particularly in R values. The results clearly demonstrated that the hydraulic conductivity can be significantly influenced by grading characteristics (d10, d20, d30, d50, d60, cu, cc, n, Io). Furthermore, comparisons between results obtained in the present study and hydraulic conductivity estimated with other formulas available in the literature were made. The comparisons indicated that the best estimation of hydraulic conductivity changes based on the gradation and shape properties of the sands tested. PMID- 27390659 TI - Comparative analysis of the terpenoid biosynthesis pathway in Azadirachta indica and Melia azedarach by RNA-seq. AB - Azadirachta indica (neem) is the only source of azadirachtin, which is known for its insecticide activity. Melia azedarach is a related species of A. indica, widely distributed in the south of China. In this study, the leaf transcriptomes of these two Meliaceae plants were sequenced. More than 40 million clean reads were generated from each library. About 80 % of A. indica reads were mapped to the neem genome, while 93 % of M. azedarach reads were mapped to its assembled transcripts and unigenes dateset. After mapping and assembly, 225,972 transcripts and 91,607 unigenes of M. azedarach were obtained and 1179 new genes of A. indica were detected. Comparative analysis of the annotated differentially expressed genes (DEG) showed that all six DEGs involved in terpenoid backbone biosynthesis were up-regulated in A. indica. Chemical analysis of the two plants revealed A. indica leaves contained 2.45 % total terpenoid and nearly 20-50 ug azadirachtin per gram, whereas azadirachtin was not detected in M. azedarach and total terpenoid content was reached 1.67 %. These results give us a better insight into the transcriptomes differences between A. indica and M. azedarach, and help us to understand the terpenoid biosynthesis pathway in vivo. PMID- 27390661 TI - Evaluation of the recurrence pattern of gastric cancer after laparoscopic gastrectomy with D2 lymphadenectomy. AB - BACKGROUND: The aim of this study was to analyze the oncological aspects of gastric cancer following laparoscopic gastrectomy with D2 lymphadenectomy (LG D2). METHODS: We retrospectively evaluated the long-term outcomes of 354 patients who underwent LG-D2 for primary gastric cancer. Recurrence patterns and predictors of peritoneal metastasis were analyzed. RESULTS: Median follow-up time was 43.8 months. Five-year overall survival rates for yp/pStages I, II, and III gastric cancer were 93.7, 78.5, and 42.2 %, respectively. Recurrence was observed in 86 patients. Peritoneal metastasis was the most frequent recurrence pattern (n = 51), followed by hepatic metastasis (n = 17). Lymphatic recurrence at distant sites was observed in 10 patients. No locoregional lymph node metastasis or local recurrence was seen. Nine of 51 cases of peritoneal recurrence were detected by probe laparoscopy. Peritoneal recurrence rates were significantly higher in yp/pT4 and yp/pN3 diseases compared with yp/pT <= 3 and yp/pN <= 2 diseases. Multivariate analyses demonstrated that yp/pT4, yp/pN3, tumor size >=70 mm, vascular invasion, and undifferentiated tumors were predictors of peritoneal recurrence following LG-D2. CONCLUSION: Long-term outcomes of gastric cancer following LG-D2, including recurrence patterns and predictors of peritoneal metastasis, were comparable to those following open D2 gastrectomy. LG-D2 showed good local control. Probe laparoscopy after LG may be effective in detecting peritoneal recurrence, which is not determined with less invasive examinations, including a CT scan. Future large-scale prospective studies are desirable to evaluate not only surgical but also oncological benefits and safety of LG-D2 for advanced gastric cancer. PMID- 27390662 TI - Representative sampling of natural biofilms: influence of substratum type on the bacterial and fungal communities structure. AB - In situ biofilm sampling is a key step for the study of natural biofilms and using methodologies that reflect natural diversity is necessary to guarantee representative sampling. Here, we focalise on the impact of the type of substrata on which biofilms grow on bacterial and fungal communities' structure. The indirect molecular approach, Denaturing Gel Gradient Electrophoresis (DGGE) of a gene fragment coding for either 16S rRNA or 28S rRNA, for bacteria or fungi respectively, was used to evaluate the variability of microbial community structures among different biofilm substrata: natural (pebbles, live plants, wood and sediment), or artificial (glass, Plexiglas((r)) and sterile wood), in a small river (the Loiret, France). Multivariate statistics, band richness and diversity indexes (Shannon and Simpson) were used to highlight variations in community structure between substrata. Results showed variations of bacterial and fungal diversity between different substrata according to substratum properties/origin (natural or artificial, organic or inorganic) but there was no optimal substratum for sampling, and artificial substrata were not significantly less applicable than natural substrata. Pooling 4 different substrata types allowed a higher bacterial and fungal biodiversity recovery. Point contact sampling may thus gain in robustness by increasing the number of substrata considered. Fungal species richness was similar to the bacterial one on most substrata which suggested they should be more frequently considered in riverine biofilm studies. PMID- 27390663 TI - Insomnia and its associations in patients with recurrent glial neoplasms. AB - BACKGROUND: Patient with neurological disorders and cancer can develop sleep disturbance, in particular insomnia. Etiology of insomnia is multi-factorial in primary brain tumour patients with possible causes including corticosteroids, psychoactive medications, co-morbid psychiatric/medical conditions, and damage to neuronal tissue. FINDINGS: To understand better insomnia in recurrent glioma patients, a single-center retrospective analysis was performed looking at recurrent glioma patients from January 2004 to May 2009. Data was extracted and included demographics, clinical factors, psychoactive medications, and co-morbid symptoms. Presence and absence of insomnia complaints was evaluated with other co morbidities using Chi square and Wilcoxon analyses. Records from 340 recurrent glioma patients were evaluated and 46.8 % (n = 159) indicated presence of insomnia with 20 % (n = 66) actively using medications for sleep. Use of corticosteroids were significantly associated with insomnia (p = 0.0003). Age, gender, tumour location, use of stimulants, antipsychotics, and antidepressants were not significantly associated with insomnia in recurrent glioma patients. There was a trend towards a possible significant association with insomnia to fatigue complaints and use of anti-epileptics, p-values of 0.0501 and 0.0725 respectively. CONCLUSIONS: In conclusion, insomnia is commonly encountered in patients with recurrent glial tumors. Corticosteroid use is associated with insomnia in this population. In light of the frequency of insomnia and its associations, future analysis is warranted into sleep complaints in recurrent glioma patients and its impact on quality of life. PMID- 27390664 TI - Periodicity and positivity of a class of fractional differential equations. AB - Fractional differential equations have been discussed in this study. We utilize the Riemann-Liouville fractional calculus to implement it within the generalization of the well known class of differential equations. The Rayleigh differential equation has been generalized of fractional second order. The existence of periodic and positive outcome is established in a new method. The solution is described in a fractional periodic Sobolev space. Positivity of outcomes is considered under certain requirements. We develop and extend some recent works. An example is constructed. PMID- 27390665 TI - Trigeminal Neuralgia Due to Red Vein Draining a Supratentorial Arteriovenous Malformation: Case Report. AB - Trigeminal neuralgia (TGN) is rarely caused by arteriovenous malformation (AVM). The AVMs causing TGN are reported mostly in the ipsilateral posterior fossa. The culprit vessels are dilated feeding artery or nidus itself. We present a rare case of TGN caused by dilated draining veins from a supratentorial AVM. The patient suffered from TGN with an incidentally found large AVM, which had been left untreated. The neuralgia was successfully relieved by microvascular decompression. Dilated red veins compressed the nerve at the root entry zone and distant cisternal portion of the nerve. Technically, transposition is not practical for fragile, dilated red veins with high pressure. Interposition is safer method in this case. PMID- 27390666 TI - Technology and Reflection: Mood and Memory Mechanisms for Well-Being. AB - BACKGROUND: We report a psychologically motivated intervention to explore Technology Mediated Reflection (TMR), the process of systematically reviewing rich digital records of past personal experiences. Although TMR benefits well being, and is increasingly being deployed, we know little about how one's mood when using TMR influences these benefits. We use theories of memory and emotion regulation to motivate hypotheses about the relationship between reflection, mood, and well-being when using technology. We test these hypotheses in a large scale month long real world deployment using a web-based application, MoodAdaptor. MoodAdaptor prompted participants to reflect on positive or negative memories depending on current mood. METHODS: We evaluated how mood and memory interact during written reflection and measured effects on well-being. We analyzed qualitative and quantitative data from 128 participants who generated 11157 mood evaluations, 5051 logfiles, 256 surveys, and 20 interviews. RESULTS: TMR regulated emotion; when participants reflected on memories with valences opposite to their current mood, their mood became more neutral. However this did not impact overall well-being. Our findings also clarify underlying TMR mechanisms. Moods and memories competed with each other; when positive moods prevailed over negative memories, people demonstrated classic mechanisms shown in prior work to influence well-being. When negative moods prevailed over positive memories, memories became negatively tainted. CONCLUSIONS: Our results have implications for new well-being interventions and technologies that capitalize on the interconnectedness of memory and emotion. PMID- 27390667 TI - Critical congenital heart disease screening. AB - Critical congenital heart disease (CCHD) is a heart lesion for which neonates require early surgical intervention to survive. Without intervention, the rates of mortality and survival with significant disability are extremely high. Early diagnosis can potentially improve health outcomes in newborns with CCHD. Until recent years, no routine screening protocol existed. In the last few years, pulse oximetry screening for CCHD in newborns has been added to the list of recommended uniform screening panels and advocated by several health-care authorities. A positive screening test result warrants an echocardiogram to evaluate for CCHD. Newborn screens do not usually require parental consent. However, most of the states mandates in the United States include a statement allowing exemption from the screen on the basis of parental religious or personal beliefs. PMID- 27390668 TI - CD10 and CD138 can be expressed in giant cell tumor of bone: An immunohistochemical study. AB - Giant cell tumor of bone (GCTB) is a primary bone neoplasm which is characterized by the presence of mononuclear cells (MCs) and osteoclast-like multinucleated giant cells (MNGCs). Up to our knowledge, CD10 immunoreactivity in GCTB has not yet been studied, and only one study touched on CD138 immunoreactivity in GCTB. The objective of this study is to investigate the immunoreactivity of CD10 and CD138 in GCTB. We offer a discussion of our findings in the context of the differential diagnosis, particularly in small biopsy material. We retrieved and reviewed 15 well-documented cases of GCTB from January 2008 to December 2014. Well-controlled standard immunohistochemical satins were performed on these cases for CD10 and CD138 and few other selected antibodies. Immunoreactivity for CD10 was membranous and was found in 14 (93%) cases. This immunoreactivity was found only in the MCs, whereas the MNGC were all negative. CD138 showed variable positivity in 11 (73%) while 4 (37%) were completely negative. Similar to CD10, staining for CD138 was only seen in the MC; however, the immunoreactivity was predominantly concentrated in the peri-vascular areas. Most of GCTB cases can show variable immunoreactivity for CD10 and CD138. The aforementioned immune expression raise the possibility of a role in the pathogenesis of GCTB. Paying attention to this immunoreactivity is recommended when considering the clinical and radiological differential diagnosis, especially in small biopsy specimens. PMID- 27390669 TI - Detection of inducible and constitutive clindamycin resistance among Staphylococcus aureus isolates in a tertiary care hospital, Eastern India. AB - INTRODUCTION: Clindamycin is an excellent drug for skin and soft tissue Staphylococcus aureus infections, but resistance mediated by inducible macrolide lincosamide-streptogramin B (iMLSB) phenotype leads to in vivo therapeutic failure even though they may be in vitro susceptible in Kirby-Bauer disk diffusion method. OBJECTIVE: The study was aimed to detect the prevalence of iMLSB phenotype among S. aureus isolates by double disk approximation test (D test) in a tertiary care hospital, Eastern India. MATERIALS AND METHODS: A total of 209 consecutive S. aureus isolates were identified by conventional methods and subjected to antimicrobial susceptibility testing by Kirby-Bauer disk diffusion method. Erythromycin-resistant isolates were tested for D-test. RESULTS: From 1282 clinical specimens, 209 nonrepeated S. aureus isolates were obtained. Majority of isolates 129 (61.7%) were methicillin-resistant S. aureus (MRSA). There was statistically significant difference between outpatients 60.1% and inpatients 39.9% (P < 0.0001). From 209 S. aureus isolates, 46 (22%) were D-test positive (iMLSB phenotype), 41 (19.6%) were D-test negative (methicillin sensitive [MS] phenotype), and 37 (17.7%) were constitutively resistant (constitutive macrolide-lincosamide-streptogramin B phenotype). The incidence of inducible, constitutive, and MS phenotype was higher in MRSA isolates compared to MS S. aureus (MSSA). The constitutive clindamycin resistance difference between MSSA and MRSA isolates were found to be statistically significant (P = 0.0086). CONCLUSION: The study revealed 22% of S. aureus isolates were inducible clindamycin resistant, which could be easily misidentified as clindamycin susceptible in Kirby-Bauer disk diffusion method. Therefore, clinical microbiology laboratory should routinely perform D-test in all clinically isolated S. aureus to guide clinicians for the appropriate use of clindamycin. PMID- 27390670 TI - Assessment of the cardiac autonomic neuropathy among the known diabetics and age matched controls using noninvasive cardiovascular reflex tests in a South-Indian population: A case-control study. AB - AIM: Diabetes mellitus is a chronic condition characterized by hyperglycemia. The objective of the study was to estimate the prevalence of cardiac autonomic neuropathy in a rural area of South India, among the known diabetics after comparing them with the age-matched healthy controls, utilizing noninvasive cardiac autonomic neuropathy reflex tests. MATERIALS AND METHODS: A case-control study was conducted for 4 months (October 2014 to January 2015) at an Urban Health and Training Center (UHTC) of a Medical College located in Kancheepuram district, Tamil Nadu. The study was conducted among 126 diagnosed Type 2 diabetes patients and in 152 age- and sex-matched healthy controls to ensure comparability between the cases and controls and, thus, reduce variability due to demographic variables. All the study subjects (cases and controls) were selected from the patients attending UHTC during the study duration, provided they satisfied the inclusion and exclusion criteria. Study participants were subjected to undergo noninvasive cardiac autonomic neuropathy reflex tests. The associations were tested using paired t-test for the continuous (mean +/- standard deviation) variables. RESULTS: The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2% (67/126). On further classification, positive (abnormal) results were obtained in 56 (sympathetic - 44.4%) and 51 (parasympathetic - 40.5%) diabetic cases. Overall, heart rate variation during deep breathing was found to be the most sensitive test to detect parasympathetic autonomic neuropathy while the diastolic blood pressure response to sustained handgrip exercise was the most sensitive method to detect sympathetic neuropathy dysfunction. CONCLUSION: The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2%. Even though cardiac autonomic neuropathy can be detected by various invasive tests, noninvasive tests remain a key tool to detect it in the remote settings in a cost-effective and user friendly manner without making people visit higher centers. PMID- 27390671 TI - Recurrent angina from chronic coronary obstruction following transcatheter aortic valve implantation. AB - Severe aortic stenosis and coronary artery disease often coexist. Coronary angiography (CA) and percutaneous coronary intervention (PCI) can be challenging in patients with prior transcatheter aortic valve implantation (TAVI). Depending on the type and position of the implanted valve, the procedure can be challenging or even unfeasible due to interference of diagnostic catheters and valve parts. The correct positioning of the TAVI prosthesis during TAVI was identified as an important factor with regard to the feasibility of subsequent CA or PCI. TAVI has been also associated with vascular, cerebrovascular and conduction complication. One is rare but life-threatening complication, coronary ostial obstruction. Coronary ostial obstruction can develop, especially if a safety check of more than 10 mm of coronary ostial height is not taken into consideration during TAVI. This complication can cause recurrent episodes of angina and can severely worsen the patient's cardiac systolic function. PMID- 27390672 TI - Victims or survivors? PMID- 27390673 TI - Ketogenic Diet, but Not Polyunsaturated Fatty Acid Diet, Reduces Spontaneous Seizures in Juvenile Rats with Kainic Acid-induced Epilepsy. AB - BACKGROUND AND PURPOSE: The high-fat, low-carbohydrate ketogenic diet (KD) is effective in many cases of drug-resistant epilepsy, particularly in children. In the classic KD, fats consist primarily of long-chain saturated triglycerides. Polyunsaturated fatty acids (PUFAs), especially the n-3 type, decrease neuronal excitability and provide neuroprotection; pilot human studies have raised the possibility of using PUFAs to control seizures in patients. METHODS: To determine the relative roles of the KD and PUFAs in an animal model, we induced epilepsy in juvenile rats (P29-35) using intraperitoneal kainic acid (KA). KA caused status epilepticus in all rats. Two days after KA, rats were randomized to one of 4 dietary groups: Control diet; PUFA diet; KD; or KD plus PUFA. All diets were administered isocalorically at 90% of the rat recommended daily calorie requirement. Spontaneous recurrent seizures (SRS) were assessed for 3 months after diet randomization. RESULTS: Rats receiving the KD or KD-PUFA diet had significantly fewer SRS than those receiving the Control diet or PUFA diet. The PUFA diet did not reduce SRS compared to the Control diet. CONCLUSIONS: In the KA epilepsy model, the KD protects against SRS occurrence but dietary enhancement with PUFA does not afford additional protection against spontaneous seizures. PMID- 27390674 TI - Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats. AB - BACKGROUND AND PURPOSE: This study aimed to investigate the effect of ceftriaxone on oxidative stress and gap junction protein (connexin 43, Cx-43) expression in pentylenetetrazole (PTZ) induced kindling model. METHODS: Twenty four Sprague dawely rats were divided into 3 equal groups (a) normal group: normal rats. (b) PTZ kindled group: received PTZ at the dose of 50 mg/kg via intraperitoneal injection (i.p.) every other day for 2 weeks (c) ceftriaxone treated group: received ceftriaxone at the dose 200 mg?kg/12 hrs via i.p. injection daily from the 6th dose of PTZ for 3 days. Racine score, latency before beginning the first myoclonic jerk and duration of the jerks used as parameters of behavioral assessment. Immunohistopathological study for Cx-43 expression in hippocampus and measurement of markers of oxidative stress (malondialdehyde [MDA], low reduced glutathione [GSH] and catalase [CAT]) in hippocampal neurons were done. RESULTS: PTZ kindling was associated with behavioral changes (in the form high stage of Racine score, long seizure duration and short latency for the first jerk), enhanced oxidative stress state (as demonstrated by high MDA, low GSH and CAT) and up regulation of Cx43 in hippocampal regions. While, ceftriaxone treatment ameliorated, significantly, PTZ-induced convulsions and caused significant improvement in oxidative stress markers and Cx-43 expression in hippocamal regions (p < 0.05). CONCLUSIONS: These findings support the anticonvulsive effects of some beta-lactams antibiotics which could offer a possible contributor in the basic treatment of temporal lobe epilepsy. This effect might be due to reduction of oxidative stress and Cx43 expression. PMID- 27390675 TI - The Difference in Heart Rate Change between Temporal and Frontal Lobe Seizures during Peri-ictal Period. AB - BACKGROUND AND PURPOSE: Heart rate (HR) change is easily seen in seizures. Tachycardia is frequently seen in temporal lobe epilepsy (TLE), rather than extra temporal lobe epilepsy (XTLE). We report the difference in the HR pattern between TLE and frontal lobe epilepsy (FLE) during peri-ictal period. METHODS: The ECG data, collected during EEG monitoring, was used. To compare the HR pattern between FLE and TLE, we investigated the baseline HR, maximum HR, seizure onset to peak HR, HR change, and the time return to baseline. RESULTS: A total of 198 seizures (FLE was 115, TLE was 83) were included in this study. The baseline HR (in TLE, 74.9 +/- 17.2 and in FLE, 70.7 +/- 11.5 bpm), there was no difference between two groups. But the mean duration of the increased HR was more prolonged in TLE group (93.8 +/- 54.9 seconds) than the FLE group(39.0 +/- 21.4 seconds) (p < 0.001), the time to peak HR of the TLE group (135.1 +/- 19.1 seconds) was higher than FLE group (119.3 +/- 19.7 seconds) (p = 0.027), and the HR change of the TLE group (60.0 +/- 26.3 bpm) was more prominent than that of the FLE group (22.8 +/- 26.2 seconds) (p < 0.001). Furthermore, a longer duration of HR increase was seen in that of the TLE group than FLE group. CONCLUSIONS: The HR change of the TLE group was more prominent and prolonged than that of the FLE group. Therefore, the HR change can be a pattern that differentiates TLE from FLE. PMID- 27390677 TI - An Atypical Presentation of Subacute Encephalopathy with Seizures in Chronic Alcoholism Syndrome. AB - Subacute encephalopathy with seizures in chronic alcoholism syndrome is a rare clinical manifestation in patients with chronic alcohol abuse. We report the case of a patient with chronic alcoholism who presented with partial nonconvulsive status epilepticus associated with a thalamic lesion. PMID- 27390676 TI - Assessment of Time and Frequency Domain Parameters of Heart Rate Variability and Interictal Cardiac Rhythm Abnormalities in Drug-naive Patients with Idiopathic Generalized Epilepsy. AB - BACKGROUND AND PURPOSE: Epilepsy is a disease known to occur with autonomous phenomenons. Earlier studies indicate decreased heart rate variability (HRV) during ictal and interictal periods among epilepsy patients. In this study, we aim to investigate cardiac rhythm abnormalities and HRV during interictal period between drug-naive patients with idiopathic generalized epilepsy (IGE) and healthy control group. METHODS: Twenty-six patients with IGE and 26 healthy individuals included in the study. In order to eliminate any structural cardiac pathology, transthoracic echocardiography was performed in all subjects and time and frequency domain parameters of HRV were evaluated after 24-hour rhythm holter monitoring. RESULTS: Between two groups, no significant difference was detected in terms of mean heart rate and maximum duration between the start of the Q waves and the end of the T waves (QT intervals). In the time domain analysis of HRV, no statically significant difference was detected for standard deviation of all R - R intervals and root-mean-square of successive differences between patient and control group (p = 0,070 and p = 0,104 respectively). In the frequency domain analysis of HRV, patients tended to display lower total power and very low frequency power than did healthy subjects, but the differences were not statistically significant. CONCLUSIONS: Our results suggest that there is no major effect of the epilepsy on HRV in patients with IGE. It should be emphasized that, in this study, HRV was evaluated only in patients with IGE and that the results are not proper to be generalized for patients with partial seizures. PMID- 27390678 TI - Intracranial Cortical Calcifications in a Focal Epilepsy Patient with Pseudohypoparathyroidism. AB - Patients with chronic parathyroid dysfunction often have intracranial calcification in deep gray matter (GM) and subcortical white matter (WM) of their brain. Some of them are also epilepsy patients. Although cortical etiologies are main cause of epileptic seizure, cortical calcification has not been reported in these patients. We report a newly diagnosed focal epilepsy patient whose brain magnetic resonance imaging revealed intracranial calcifications in cortical as well as subcortical areas. Blood lab revealed that he had hypocalcemia due to pseudohypoparathyroidism. Video EEG monitoring revealed the ictal EEG mainly consist of polymorphic delta to theta waves with maximum at right temporal area followed by background attenuation and muscle artifacts. The interictal EEG showed multiple focal spike-wave discharges. After given oral calcium and calcitriol supplement, his calcium and phosphorous level normalized and he remains seizure free. This is the first case to show cortical calcification in a patient with pseudohypoparathyroidism. Cortical calcification could be an important measure of seizure burden in these patients and thus sophisticated imaging protocols should be used to visualize the extent of calcium deposits. PMID- 27390679 TI - A Case of Phenytoin-induced Rhabdomyolysis in Status Epilepticus. AB - Phenytoin is a commonly used antiepileptic drug, especially when treating status epilepticus. Here, we present a patient who suffered from status epilepticus and developed rhabdomyolysis after being treated with phenytoin. As multiple seizures itself can induce rhabdomyolysis, it is difficult to recognize that phenytoin can be the cause of rhabdomyolysis in status epilepticus patients. Even though phenytoin is a rare cause of rhabdomyolysis, we should discern that phenytoin can be a causative drug to bring about rhabdomyolysis. PMID- 27390680 TI - Supra-recommendation Treatment of Super-refractory Status Epilepticus. AB - A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India. PMID- 27390681 TI - Atrophy is a Real Phenomenon that Can Result in Changes in Deep Brain Stimulation Outcome. PMID- 27390682 TI - Artificial neural networks versus bivariate logistic regression in prediction diagnosis of patients with hypertension and diabetes. AB - BACKGROUND: Diabetes and hypertension are important non-communicable diseases and their prevalence is important for health authorities. The aim of this study was to determine the predictive precision of the bivariate Logistic Regression (LR) and Artificial Neutral Network (ANN) in concurrent diagnosis of diabetes and hypertension. METHODS: This cross-sectional study was performed with 12000 Iranian people in 2013 using stratified- cluster sampling. The research questionnaire included information on hypertension and diabetes and their risk factors. A perceptron ANN with two hidden layers was applied to data. To build a joint LR model and ANN, SAS 9.2 and Matlab software were used. The AUC was used to find the higher accurate model for predicting diabetes and hypertension. RESULTS: The variables of gender, type of cooking oil, physical activity, family history, age, passive smokers and obesity entered to the LR model and ANN. The odds ratios of affliction to both diabetes and hypertension is high in females, users of solid oil, with no physical activity, with positive family history, age of equal or higher than 55, passive smokers and those with obesity. The AUC for LR model and ANN were 0.78 (p=0.039) and 0.86 (p=0.046), respectively. CONCLUSION: The best model for concurrent affliction to hypertension and diabetes is ANN which has higher accuracy than the bivariate LR model. PMID- 27390683 TI - Determinants of healthcare expenditures in Iran: evidence from a time series analysis. AB - BACKGROUND: A dramatic increase in healthcare expenditures is a major health policy concern worldwide. Understanding factors that underlie the growth in healthcare expenditures is essential to assist decision-makers in finding best policies to manage healthcare costs. We aimed to examine the determinants of healthcare spending in Iran over the periods of 1978-2011. METHODS: A time series analysis was used to examine the effect of selected socio-economic, demographic and health service input on per capita healthcare expenditures (HCE) in Iran from 1978 to 2011. Data were retrieved from the Central Bank of Iran, Iranian Statistical Center and World Bank. Autoregressive distributed lag approach and error correction method were employed to examine long- and short-run effects of covariates. RESULTS: Our findings indicated that the GDP per capita, degree of urbanization and illiteracy rate increase healthcare expenditures, while physician per 10,000 populations and proportion of population aged>= 65 years decrease healthcare expenditures. In addition, we found that healthcare spending is a "necessity good" with long- and short-run income (GDP per capita), elasticities of 0.46 (p<0.01) and 0.67 (p = 0.01), respectively. CONCLUSION: Our analysis identified GDP per capita, illiteracy rate, degree of urbanization and number of physicians as some of the driving forces behind the persistent increase in HCE in Iran. These findings provide important insights into the growth in HCE in Iran. In addition, since we found that health spending is a "necessity good" in Iran, healthcare services should thus be the object of public funding and government intervention. PMID- 27390684 TI - Does the theory-driven program affect the risky behavior of drug injecting users in a healthy city? A quasi-experimental study. AB - BACKGROUND: The horror of HIV/AIDS as a non-curable, grueling disease is a destructive issue for every country. Drug use, shared needles and unsafe sex are closely linked to the transmission of HIV/AIDS. Modification or changing unhealthy behavior through educational programs can lead to HIV prevention. The aim of this study was to evaluate the efficiency of theory-based education intervention on HIV prevention transmission in drug addicts. METHODS: In this quasi-experimental study, 69 male drug injecting users were entered in to the theory- based educational intervention. Data were collected using a questionnaire, before and 3 months after four sessions (group discussions, lecture, film displaying and role play) of educational intervention. RESULTS: The findings signified that the mean scores of constructs (self-efficacy, susceptibility, severity and benefit) significantly increased after the educational intervention, and the perceived barriers decreased (p< 0.001). Also, the history of HIV testing was reported to be 9% before the intervention, while the rate increased to 88% after the intervention. CONCLUSION: The present research offers a primary founding for planning and implementing a theory based educational program to prevent HIV/AIDS transmission in drug injecting addicts. This research revealed that health educational intervention improved preventive behaviors and the knowledge of HIV/AIDS participants. PMID- 27390685 TI - Factors affecting the informal payments in public and teaching hospitals. AB - BACKGROUND: Informal payments in the health sector of many developing countries are considered as a major impediment to health care reforms. Informal payments are a form of systemic fraud and have adverse effects on the performance of the health system. In this study, the frequency and extent of informal payments as well as the determinants of these payments were investigated in general hospitals affiliated to Tehran University of Medical Sciences. METHODS: In this cross sectional study, 300 discharged patients were selected using multi-stage random sampling method. First, three hospitals were selected randomly; then, through a simple random sampling, we recruited 300 discharged patients from internal, surgery, emergency, ICU & CCU wards. All data were collected by structured telephone interviews and questionnaire. We analyzed data using Chi- square, Kruskal-Wallis and Mann-Whitney tests. RESULTS: The results indicated that 21% (n=63) of individuals paid informally to the staff. About 4% (n=12) of the participants were faced with informal payment requests from hospital staff. There was a significant relationship between frequency of informal payments with marital status of participants and type of hospitals. According to our findings, none of the respondents had informal payments to physicians. The most frequent informal payments were in cash and were made to the hospitals' housekeeping staff to ensure more and better services. There was no significant relationship between the informal payments with socio-demographic characteristics, residential area and insurance status. CONCLUSION: Our findings revealed that many strategies can be used for both controlling and reducing informal payments. These include training patients and hospitals' staff, increasing income levels of employees, improving the quantity and quality of health services and changing the entrenched beliefs that necessitate informal payments. PMID- 27390686 TI - The productivity and its barriers in public hospitals: case study of ran. AB - BACKGROUND: Due to the increasing health care costs, the issue of productivity in hospitals must be taken into great consideration in order to provide, preserve and promote public health services. Thus, increasing the level of productivity must become the main aim of any hospital. Objective of this study is to determine the total factor productivity and its components over the period under the study. METHODS: In this cross sectional study, total factor productivity changes of hospitals affiliated to Tehran University of Medical Sciences were measured according to Malmquist index over the period 2009-2014. To estimate total productivity changes using Data Envelopment Analysis method, inputoriented and variable return to scale assumptions were applied and Deap2.1 software was used. RESULTS: The mean value of total productivity changes was 1.013. It means that during the study period the productivity experienced a 1.3% decrease. Technological efficiency changes have the greatest influence on productivity decrease than the other factors. Scale efficiency, managerial efficiency and technical efficiency changes were ranked. CONCLUSION: Lack of knowledge of hospital personnel on proper application of technology in patient treatment is the main factor leading to productivity decrease resulting from technological changes in the studied hospitals. Therefore, holding courses for personnel in order to teach them the proper use of technology in diagnosis and patient care can be helpful. PMID- 27390688 TI - Health technology assessment of image-guided radiotherapy (IGRT): A systematic review of current evidence. AB - BACKGROUND: Image-guided radiotherapy used multiple imaging during the radiation therapy course to improve the precision and accuracy of health care provider's treatment. OBJECTIVES: This study aims to assess the safety, effectiveness and economic aspects of image-guided radiation therapy for decision-making about this technology in Iran. METHODS: In this study, the most important medical databases such as PubMed and Cochrane Library were searched until November 2014. The systematic reviews, health technology assessment reports and economic evaluation studies were included. The results of included studies were analyzed via the thematic synthesis. RESULTS: Seven articles were included in the study. The results showed that image-guided radiation therapy, regardless of the imaging technique used in it, is associated with no major toxicity and has the potential to reduce the symptoms of poisoning. Using image-guided radiation therapy for prostate cancer resulted in substantial improvement in the quality of the received dose and optimal therapeutic dose of radiation to the targeted tumor while the radiation dose to the surrounding healthy tissues was minimal. Additionally, image-guided radiation therapy facilitated the diagnosis and management of exception deviations, including immediate changes and gross errors, weight loss, significant limbs deformity, systematic changes in the internal organs and changes in respiratory movements. Usage of image-guided radiation therapy for prostate cancer was associated with increased costs. CONCLUSION: Current available evidence suggests that the image-guided radiation therapy can reduce the amount of radiation to healthy tissue around the tumor and the toxicity associated with it. This can enhance the safe dose of radiation to the tumor and increase the likelihood of destruction of tumor. The current level of evidence required conducting further studies on the costs and effectiveness of this technology compared with conventional technology. PMID- 27390687 TI - Degarelix for the treatment of advanced prostate cancer compared with GnRh Agonists: a systematic review and meta-analysis. AB - BACKGROUND: Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. We performed a systematic review to compare safety, efficacy and effectiveness of degarelix, a new gonadotropin releasing hormone (GnRH) antagonist (blocker), versus gonadotropin-releasing hormone (GnRH) agonists. METHODS: MEDLINE, Web of Science and the Cochrane library were searched to identify all of the published Randomized Controlled Trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists with or without anti-androgen therapy for the treatment of prostate cancer. We performed meta-analysis of extracted data on safety and efficacy of the target medication. RESULTS: Six studies were included. They involved a total of 2296 patients which were used in the meta-analysis. Follow-up times after treatment were between 12 weeks and 12 months. Three of six RCTs compared degarelix with goserelin and the others compared it with leuprolide. Meta-analysis on safety outcomes revealed that the only statistically significant difference between the degarelix treated group and GnRH agonists treated group was complication in the injection site which was higher in degarelix-treated group (OR= 46.34, 95% CI: 15.79 to 136, p<0.001). Although general mortality rate was lower in degarelix treated group (OR= 2.06, 95% CI: 1.08 to 3.93, p=0.03); mortality due to the drug side effects was not different. Meta-analysis of efficacy data also showed that International Prostate Symptom Score (IPSS) reduction at week 12, (MD=-1.85, 95% CI: -2.97 to - 0.72, p=0.001) and Testosterone reduction between day 1-28, (OR=11.58, 95% CI: 5.77 to 23.22, p<0.001) was statistically higher in degarelix treated group. Testosterone reduction after day 28 and prostate volume reduction did not have significant difference. CONCLUSION: Our meta-analysis indicates that, compared with GnRH agonists, degarelix has significantly more effects on lower urinary tract symptoms and also Prostate Specific Antigen (PSA) and testosterone reduction in the first month of the treatment. Except minor complications in the injection site like pain, erythema and swelling, there is no increase in major side effects and mortality due to degarelix. This is while the effect on testosterone and PSA after the first month of treatment is not statistically different between the two groups. PMID- 27390689 TI - Safety, effectiveness and economic aspects of maggot debridement therapy for wound healing. AB - BACKGROUND: Maggot therapy has recently attracted considerable attention as an emerging debridement technique for wound healing. This study aimed to review the safety, effectiveness and economic evaluations of Maggot Debridement Therapy for wound healing. METHODS: To retrieve the relevant evidences, the Cochrane Library (until September 2014) was searched by appropriate keywords, using free text and Mesh. Systematic reviews, HTA reports and economic evaluation studies that compared larval therapy with other debridement therapies, such as hydrogel in patients with various kinds of ulcers in terms of side effects, the wound healing rate, the healing time, and cost per QALY, were included. RESULTS: Five studies met the inclusion criteria which showed that healing with larval therapy happened a little earlier than the usual methods and that pain perception in larval therapy was a little more than usual methods (as by anesthetic conventional methods). However, the quality of life of those patients who received larval therapy was better and they showed a greater tendency to larval therapy as it was relatively safe and had a low rate of side effects. CONCLUSION: It seems that larval therapy has several advantages such as rapid wound debridement, infection elimination, pain control and ulcer healing. The use of larval therapy has the potential to reduce side effects and decrease the need for amputation. PMID- 27390690 TI - Visfatin level in patients with colorectal adenoma. AB - BACKGROUND: Visfatin is an adipocytokine secreted by visceral adipose tissue. It has been shown that adipocytokines may contribute to the induction of carcinogens and progression of tumors. Previously, we found a significant increase in the visfatin serum level in colorectal cancer patients. Herein, we investigated if this cytokine increases in patients with colorectal adenoma as a precursor of colorectal cancer. METHODS: In this case-control analytic study, a total of 34 patients diagnosed with colorectal adenoma and 35 disease-free controls were included. Adenomas were also categorized based on their location within the colon. Visfatin serum levels were measured in all cases and controls using enzyme linked immunosorbent assay kits. In order to compare visfatin levels between groups a twotailed t-test was considered. Pearson correlation was also used to assess the relationship between visfatin levels and other measured variables. RESULTS: Patients included 18 male (53%) and 16 female (47%) with a mean+/-SD age of 48.3+/-10.96 years and controls were 18 male (51%) and 17 female (49%) with a mean+/-SD age of 51.6+/-12.52 years. There were no significant difference in terms of the visfatin level between the two groups (6.7+/-3.01 ng/ml for patients and 6.8+/-2.49 ng/ml for controls, p>0.05). Except for a significant correlation between the BMI and visfatin level (p=0.041), no other correlation was detected. We found no significant difference between the levels of visfatin in each location of adenoma comparing the healthy controls (p>0.05 in all comparisons). There was no statistical difference between the locations groups in terms of visfatin level as well (p>0.05). CONCLUSION: Visfatin serum level does not significantly increase in patients with colorectal adenoma. Site of adenoma within the colon or rectum does not seem to play an important role in this regard as well. PMID- 27390691 TI - Health technology assessment in Iran: Barriers and solutions. AB - BACKGROUND: Health technology assessment (HTA) is a tool utilized for efficient dissemination of technology. For the purpose of encouraging decision-makers to utilize this tool, at first, we need to identify the obstacles in the processes of preparation, utilization, and implementation of HTAs. This study aims to define these barriers and offer solutions for effective utilization of HTA reports produced in Iran. METHODS: This qualitative content analysis determines the various beneficiaries of HTA, and utilizes a semi-structured interview with the participants who are all involved in the HTA. RESULTS: Nine out of ten people invited for the interviews accepted the researchers' invitation. An analysis of barriers and solutions for improving the utilization of HTA reports was conducted in three levels of policy makers (policy level), specialists in healthcare (professional level), and ordinary people (public level). The barriers in the policy level include unsuitability of reports for their audience, incompatible views toward the definition and necessity of health technology assessment, lack of financial resources for report preparation, and limitations in large-scale policymaking in Ministry of Health. Barriers in the professional level include lack of knowledge on HTA among serviceproviders. Barriers in the public level consist of information asymmetry. CONCLUSION: There are various barriers toward accurate utilization of HTAs in Iran. Thus, a systematic approach which involves people, brings about culture, improves infrastructures, and boosts supervision on the performance is recommended. PMID- 27390693 TI - Achievements and future path of Tehran municipality in urban health domain: An Iranian experience. AB - BACKGROUND: According to national laws and world experiences; provision, maintenance, and improving citizens' health are considered to be the essential functions of municipalities as a "social institute". In order to equitably promote health conditions at urban level, particularly in marginal areas, since 2004 targeted efforts have been implemented in the municipality of Tehran metropolis. This study was intended to identify and analyze these targeted measures and tries to analyze health interventions in a conceptual framework and propose a future path. METHODS: This is a qualitative study with content analysis approach. Reviewing documents and structured interviews with national health policy making and planning experts and executive managers of 22-region municipalities of Tehran metropolis were used to collect data. The data were analyzed on the basis of conceptual framework prepared for urban health in 4 domains including municipal interventions, goal achievements, drivers and obstacles of success, and the way forward. RESULTS: From the viewpoint of interviewees, these new health actions of Tehran municipality are more based on public participation and the municipality was able to prioritize health issue in the programs and policies of Tehran city council. Tehran municipality has accomplished three types of interventions to improve health, which in orders of magnitude are: facilitative, promotional, and mandatory interventions. Development and institutionalization of public participation is the greatest achievement in health-oriented actions; and expansion of environmental and physical health-oriented facilities and promoting a healthy lifestyle are next in ranks. CONCLUSION: Since management alterations seriously challenges institutionalization of actions and innovations especially in the developing countries, it is suggested that mayors of metropolitan cities like Tehran document and review municipal health measures as soon as possible and while eliminating overlapping of interventions with other sectors, design and approve the charter of "health promoting municipality". The most important role of municipalities in this charter would be coordinating health improvement of citizens. This charter, when approved as a national policy could be used for other cities too. PMID- 27390692 TI - Prevalence of hepatic steatosis and associated factors in Iranian patients with chronic hepatitis C. AB - BACKGROUND: Hepatic steatosis is commonly observed in patients with chronic hepatitis C (CHC). Many studies indicate a relationship between steatosis and fibrosis progression. The aim of this study was to analyze the prevalence of hepatic steatosis and related factors in Iranian CHC patients. METHODS: One hundred and fifteen consecutive patients with CHC were enrolled which were treatment- naive. The patients were divided into groups with and without steatosis according to the result of liver biopsy (58.3% and 41.7%, respectively). Demographic, histological, biochemical and virological factors were examined and compared in all patients. RESULTS: In terms of host factors, body mass index (BMI), triglyceride, fasting blood glucose (FBG), necroinflammatory activity and severity in fibrosis of CHC patients with steatosis was significantly higher than the patients without steatosis. Of viral factors, HCV viral load was not significantly altered in patients with steatosis. Moreover, HCV genotypes did not meet such association. Using multivariate regression analysis, parameters of BMI values, FBG level and stage of fibrosis were independently associated with steatosis. CONCLUSION: Our data indicate that CHC patients are more susceptible to development of hepatic steatosis. Based on our results, grade of steatosis appears to be associated with hepatic fibrosis progression rate in CHC patients. PMID- 27390694 TI - Prevalence of ulnar-to-median nerve motor fiber anastomosis (Riche-Cannieu communicating branch) in hand: An electrophysiological study. AB - BACKGROUND: Two main muscles studied in the hand for evaluation of median nerve injuries are opponens pollicis (OP) and abductor pollicis brevis (APB). However, Riche-Cannieu communicating branch (RCCB) may limit the use of these muscles in electrodiagnosis. This condition is confusing in the case of median nerve injuries. This study was conducted to evaluate the prevalence of RCCB. METHODS: Twenty-three consecutive cases of complete median nerve injury were studied. Evoked responses via stimulation of median and ulnar nerves in the wrist and recording with needle in the thenar area were studied. RESULTS: Of the patients, 82.6% exhibited RCCB. In 14 (60.8%) cases the OP and in 19(82.6%) cases APB was supplied by the ulnar nerve. CONCLUSION: RCCB was detected to be 60.8% in OP and 82.6% in APB, so OP is preferable to APB in the study of median nerve. PMID- 27390695 TI - Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review and meta-analysis. AB - BACKGROUND: The aim of this study was to directly compare efficacy of atomoxetine and methylphenidate in treatment of children and adolescents 6- 18 years. METHODS: All published, randomized, open label or double blind trials, comparing the efficacy of methylphenidate with atomoxetine in treatment of children diagnosed with ADHD, using DSM-IV criteria were included in this study; ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS) scores was used. The standardized mean difference (SMD) was used as a measure of effect size. RESULTS: Eleven studies were included with a total of 2,772 participants. The meta-analysis did not find a significant difference in the efficacy between methylphenidate and atomoxetine (SMD= 0.09, 95% CI -0.06, 0.25) (Z= 1.18, p= 0.24). Sub group analysis showed a significant standardized mean difference favoring OROS methylphenidate (SMD= 0.31, 95% CI 0.16, 0.47 (Z= 3.91, p< 0.0001); immediate release methylphenidate was not superior to atomoxetine (SMD= -0.05, 95% CI -0.20, 0.10) (Z= 0.68, p= 0.49). Open label trials did not make a difference in the standardized mean difference (SMD= 0.10, 95% CI -0.02, 0.23) (Z= 1.17, p= 0.09). There was significant heterogeneity among the studies (p= 0.003, I2= 63%). Subgroup analysis demonstrated that heterogeneity was because of the open label trials (p= 0.009, I2= 79%). CONCLUSION: Atomoxetine and methylphenidate showed comparable efficacy in the treatment of children and adolescents with ADHD. However, Osmotic (Controlled) Release Oral (Delivery) System (OROS) methylphenidate is more effective than atomoxetine in treatment of ADHD in children and adolescents that is suggested as a first-line treatment in ADHD. Moreover, comparing the immediate release (IR) methylphenidate to atomoxetine did not lead to the benefit of IR methylphenidate. PMID- 27390696 TI - Cost effectiveness of type 2 diabetes screening: A systematic review. AB - BACKGROUND: Although studies reported diabetes mellitus screening cost effective, the mass screening for type2 diabetes remains controversial. In this study we reviewed the recently evidence about the cost effectiveness of mass screening systematically. METHODS: We reviewed the MEDLINE, Scopus, Web of Science (WOS), and Cochrane library databases by MeSH terms to identify relevant studies from 2000 to 2013. We had 4 inclusion and 6 exclusion criteria and used the Drummond's checklist for appraising the quality of studies. RESULTS: The initial search yielded 358 potentially related studies from selected databases. 6 studies met our inclusion and exclusion criteria and included in final review. 3 and 2 of them were conducted in Europe and America and only one of them in Asia. Quality adjusted life year (QALY) was the main outcome to appraise the effectiveness in the studies. Incremental cost effectiveness ratio (ICER) was computed in range from $516.33 to $126,238 per QALY in the studies. CONCLUSION: A review of previous diabetes screening cost effectiveness analysis showed that the studies varied in some aspects but reached similar conclusions. They concluded that the screening may be cost effective, however further studies is required to support the diabetes mass screening. PMID- 27390697 TI - Economic evaluation of test-and-treat and empirical treatment strategies in the eradication of Helicobacter pylori infection; A Markov model in an Iranian adult population. AB - BACKGROUND: Helicobacter pylori may cause many gastrointestinal problems in developing countries such as Iran. We aimed to analyze the cost- effectiveness and cost- utility of the test-and-treat and empirical treatment strategies in managing Helicobacter pylori infection. METHODS: This was a Markov based economic evaluation. Effectiveness was defined as the symptoms free numbers and QALYs in 100,000 hypothetical adults. The sensitivity analysis was based on Monte Carlo approach. RESULTS: In the test- and- treat strategy, if the serology is the first diagnostic test vs. histology, the cost per symptoms free number would be 291,736.1 Rials while the cost per QALYs would be 339,226.1 Rials. The cost per symptoms free number and cost per QALYs when the 13 C-UBT was used as the first diagnostic test vs. serology was 1,283,200 and 1,492,103 Rials, respectively. In the empirical strategy, if histology is used as the first diagnostic test vs. 13 CUBT, the cost per symptoms free numbers and cost per QALYs would be 793,234 and 955,698 Rials, respectively. If serology were used as the first diagnostic test vs. histology, the cost per symptoms free and QALYs would be 793,234 and 368941 Rials, respectively. CONCLUSION: There was no significant and considerable dominancy between the alternatives and the diagnostic tests. PMID- 27390698 TI - The effect of alendronate treatment on cortical thickness of the proximal femur in postmenopausal women. AB - BACKGROUND: Bisphosphonates (BPs) are used extensively for managing the osteoporosis. There are some controversies on atypical fractures of femur that associated with increase in cortical thickness (CT) and BPs' use. In this study, the effects of alendronate consumption were studied on femoral CT as a predictor for atypical fracture. METHODS: Forty nine post-menopausal women aged 50-70 years with osteopenia-osteoporosis who were treated with alendronate 70 mg/week for at least one year were compared to 49 controls for CT in subtrochanteric region of femur by hip dual-energy X-ray absorptiometry (DXA) scans and hip Xray. CT and its ratio were measured at 3.5 and 4.0 cm below the tip of the greater trochanter (GT) and 0.5 cm below lesser trochanter (LT) in DXA and at 9.5 and 10.5 cm of GT and 1 cm of LT in Xray. RESULTS: In this study, 98 women participated whose mean age and age at menopause were 60 (17+/-5.6) and 49 (40+/-2.7) years, respectively. Duration of BP consumption in alendronate group was 1.76+/-1.38 (1 10) years. No difference was seen in the mean of CT and its ratio between the alendronate and control groups in BMD scan or X-ray. The best correlation between two imaging modalities was in cortical ratio in 3.5 cm of GT in BMD scan and 9.5 cm of GT in X-ray. CONCLUSION: Alendronate treatment did not appear to increase femoral CT throughout the detection limits of BMD scan or X-ray. PMID- 27390699 TI - The health systems' priority setting criteria for selecting health technologies: A systematic review of the current evidence. AB - BACKGROUND: In the recent years, using health technologies to diagnose and treat diseases has had a considerable and accelerated growth. The proper use of these technologies may considerably help in the diagnosis and treatment of different diseases. On the other hand, unlimited and unrestricted entry of these technologies may result in induced demand by service providers. The aim of this study was to determine the appropriate criteria used in health technologies priority-setting models in the world. METHODS: Using MESH and free text, we sought and retrieved the relevant articles from the most appropriate medical databases (the Cochrane Library, PubMed and Scopus) through three separate search strategies up to March 2015. The inclusion criteria were as follows: 1) Studies with specific criteria; 2) Articles written in English; 3) Those articles conducted in compliance with priority setting of health technologies. Data were analyzed qualitatively using a thematic synthesis technique. RESULTS: After screening the retrieved papers via PRISMA framework, from the 7,012 papers, 40 studies were included in the final phase. Criteria for selecting health technologies (in pre assessment and in the assessment phase) were categorized into six main themes: 1) Health outcomes; 2) Disease and target population; 3) Technology alternatives; 4) Economic aspects; 5) Evidence; 6) and other factors. "Health effects/benefits" had the maximum frequency in health outcomes (8 studies); "disease severity" had the maximum frequency in disease and target population (12 studies); "the number of alternatives" had the maximum frequency in alternatives (2 studies); "cost-effectiveness" had the maximum frequency in economic aspects (15 studies); "quality of evidence" had the maximum frequency in evidence (4 studies); and "issues concerning the health system" had the maximum frequency in other factors (10 studies). CONCLUSION: The results revealed an increase in the number of studies on health technologies priority setting around the world, and emphasized the necessity of application of a multi- criteria approach for appropriate decision making about healthcare technologies in the health systems. PMID- 27390700 TI - Economic evaluation of resistant major depressive disorder treatment in Iranian population: a comparison between repetitive Transcranial Magnetic Stimulation with electroconvulsive. AB - BACKGROUND: It is estimated that major depression disorders constitute 8.2% of years lived with disability (YLDs) globally. The repetitive Transcranial Magnetic Stimulation (rTMS) and Electroconvulsive Therapy (ECT) are two relative common interventions to treat major depressive disorders, especially for treatment resistant depression. In this study the cost- effectiveness and cost-utility of rTMS were compared with ECT in Iranian population suffering from major depressive disorder using a decision tree model. METHODS: A decision tree model conducted to compare the cost-effectiveness ratio of rTMS with ECT in a health system prospective and 7 months' time horizon. The outcome variables were: response rate, remission rate and quality-adjusted life-years (QALYs) of the rTMS and ECT as primary and secondary outcomes extracted from systematic reviews and randomized control trials. The costs were also calculated through a field study in one clinic and one hospital; the direct costs have only been considered. RESULTS: The total cost for rTMS and ECTstrategieswere11015000Rials (373US$) and 11742700 Rials (397.7US$), respectively. Also the rTMS/ECT ratio of costs per improved patients was 1194410Rials (40.5 US$); the ratio for costs per QALYs utility was 21017139 Rials (711.72 US$). The incremental cost- effectiveness ratio of rTMS versus ECT was 1194410 Rials (40.44 US$) after treatment and maintenance courses. CONCLUSION: Given the current prevalence of depressive disorders in Iranian population, the ECT is more cost-effective than TMS. The sensitivity analysis showed that if the prevalence of major depressive disorders declines to below 5% or the costs of rTMS decrease (rTMS provided by public sector), then the rTMS becomes more cost-effective compared with ECT. However, efficacy of rTMS depends on the frequency of pulsed magnetic field, the location of rTMS on the head, the number of therapeutic sessions and the length of each session. PMID- 27390701 TI - EOS imaging versus current radiography: A health technology assessment study. AB - BACKGROUND: EOS is a 2D/3D muscle skeletal diagnostic imaging system. The device has been developed to produce a high quality 2D, full body radiographs in standing, sitting and squatting positions. Three dimensional images can be reconstructed via sterEOS software. This Health Technology Assessment study aimed to investigate efficacy, effectiveness and cost-effectiveness of new emerged EOS imaging system in comparison with conventional x-ray radiographic techniques. METHODS: All cost and outcome data were assessed from Iran's Ministry of Health Perspective. Data for clinical effectiveness was extracted using a rigorous systematic review. As clinical outcomes the rate of x-ray emission and related quality of life were compared with Computed Radiography (CR) and Digital Radiography (DR). Standard costing method was conducted to find related direct medical costs. In order to examine robustness of the calculated Incremental Cost Effectiveness Ratios (ICERs) we used two-way sensitivity analysis. GDP Per capita of Islamic Republic of Iran (2012) adopted as cost-effectiveness threshold. RESULTS: Review of related literature highlighted the lack of rigorous evidence for clinical outcomes. Ultra low dose EOS imaging device is known as a safe intervention because of FDA, CE and CSA certificates. The rate of emitted X-ray was 2 to 18 fold lower for EOS compared to the conventional techniques (p<0.001). The Incremental Cost Effectiveness Ratio for EOS relative to CR calculated $50706 in baseline analysis (the first scenario) and $50714, $9446 respectively for the second and third scenarios. Considering the value of neither $42146 as upper limit, nor the first neither the second scenario could pass the cost effectiveness threshold for Iran. CONCLUSION: EOS imaging technique might not be considered as a cost-effective intervention in routine practice of health system, especially within in-patient wards. Scenario analysis shows that, only in an optimum condition such as lower assembling costs and higher utilization rates, the device can be recruited for research and therapeutic purposes in pediatric orthopedic centers. PMID- 27390702 TI - The safety and effectiveness of the current treatment regimen with or without roflumilast in advanced COPD patients: A systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease, which reduces the lung function and causes respiratory symptoms over time, and it is primarily associated with shortness of breath, cough and sputum production. Roflumilast, which is a long-acting selective inhibitor, reduces the anti-inflammatory effect of the main symptoms of COPD. The aim of this study was to compare the clinical effectiveness of adding roflumilast to the current treatment regimen of patients with severe COPD. METHODS: To retrieve the marker studies, medical databases were searched up to February 2014. We included studies, which compared the clinical effectiveness and safety of roflumilast as concomitant to Long-acting beta2-agonist/Long-acting muscarinic antagonist (LABA/LAMA) regimen, in adult patients with severe COPD. The number of exacerbations, changes in the lung function FEV1, FEV1/FVC and quality of life were the major predefined outcomes. Meta-analysis of outcomes was performed by the RevMan software, with I(2)> 50%, representing considerable heterogeneity. RESULTS: Seven randomized controlled trials and two systematic reviews were included. In terms of safety, participants were likely to experience more side effects from roflumilast compared to placebo, particularly gastrointestinal effects (diarrhea, nausea, vomiting), headache and weight loss. There was no significant difference in the risk of cardiac complications or flu-like symptoms or upper respiratory tract infection in the two groups. In terms of effectiveness, only a small improvement was observed in SGRQ (St George's Respiratory Questionnaire) index. Roflumilast reduced moderate to severe attacks, and caused significant improvements in the lung function regardless of the severity of the disease and the concurrent use of other standard COPD therapies. CONCLUSION: Roflumilast anti-inflammatory therapy reduces the chronic bronchitis symptoms in patients with moderate to severe COPD, and it can be safely used with other drugs simultaneously. PMID- 27390703 TI - Development and validation of Iranian children's participation assessment scale. AB - BACKGROUND: Participation is mostly cultural and familial based, and there is not any assessment scales for evaluating kids' participation in Iranian context, therefore the purpose of this study was developing children's participation assessment scale for Iranian children. METHODS: Development of this scale occurred in two phases; phase I: planning: following reviewing the literature and adopting and compiling some items of available evaluation tools in the area (such as CAPE, CPQ, CLASS, Life-H) and receiving advice from two expert panels, the preliminary94- item questionnaire was prepared. Phase II: construct: the survey study was carried out on40 children and 21 of their parents to assess the popularity of the activity in Iran; thus, the items of the questionnaire reduced to 92 and after face and content validity, the final version prepared with 71 items. RESULTS: The final 71-item questionnaire was developed in two parent report and child-report versions. The 71 items based on the literature and expert panels' advice were categorized in 8 areas of occupation according to Occupational Therapy Practice Framework (ADL, IADL, Play, leisure, social participation, education, work, and sleep/rest). CONCLUSION: Iranian children's participation assessment is a useful and culturally relevant tool to measure participation of Iranian children. It can be used in rigorous clinical and population-based research. PMID- 27390704 TI - A survey of clinical practice patterns in diagnosis and management of Cushing's disease in Iran. AB - BACKGROUND: Cushing's disease is the most prevalent cause of endogenous adrenocorticotrophic hormone hypersecretion. The aim of this study was to document the current clinical practice pattern in the management of Cushing's disease by Iranian Endocrinologists to determine their opinions and compare them with the current clinical practice guidelines. METHODS: An eight-item questionnaire dealing with diagnosis, treatment and follow up of patients with Cushing's disease was developed, piloted, and sent to the members of Iranian Endocrinology Society. RESULTS: Among 90 endocrinologists invited to participate in the survey, 76 replied. Most respondents selected overnight dexamethasone suppression test (ONDST) and assessment of 24-hour urinary free cortisol (UFC) as the best screening tests followed by midnight serum cortisol and midnight salivary cortisol. Classic high dose dexamethasone suppression test and measurement of serum ACTH were selected for localization of the primary lesion by 64.5%. The primary choice of treatment was trans-sphenoidal pituitary surgery (86.8%). For the recurrence of Cushing's disease, the preferred treatment modality was medical therapy followed by bilateral adrenalectomy, and pituitary re-surgery. In case of treatment failure after the first pituitary surgery and ketoconazole treatment, 51% chose bilateral adrenalectomy, while36.8% selected pasireotide only. CONCLUSION: ONDST and UFC are two most common tests used to screen an index case with signs and symptoms of hypercortisolism. The primary choice of treatment in Cushing's disease is pituitary surgery. However, medical treatment by ketokonazol is preferred for the recurrences. Pasireotide is the second alternative after bilateral adrenalectomy in case of treatment failure after pituitary surgery and ketoconazole. PMID- 27390705 TI - Developing the Persian version of the homophone meaning generation test. AB - BACKGROUND: Finding the right word is a necessity in communication, and its evaluation has always been a challenging clinical issue, suggesting the need for valid and reliable measurements. The Homophone Meaning Generation Test (HMGT) can measure the ability to switch between verbal concepts, which is required in word retrieval. The purpose of this study was to adapt and validate the Persian version of the HMGT. METHODS: The first phase involved the adaptation of the HMGT to the Persian language. The second phase concerned the psychometric testing. The word-finding performance was assessed in 90 Persian-speaking healthy individuals (20-50 year old; 45 males and 45 females) through three naming tasks: Semantic Fluency, Phonemic Fluency, and Homophone Meaning Generation Test. The participants had no history of neurological or psychiatric diseases, alcohol abuse, severe depression, or history of speech, language, or learning problems. RESULTS: The internal consistency coefficient was larger than 0.8 for all the items with a total Cronbach's alpha of 0.80. Interrater and intrarater reliability were also excellent. The validity of all items was above 0.77, and the content validity index (0.99) was appropriate. The Persian HMGT had strong convergent validity with semantic and phonemic switching and adequate divergent validity with semantic and phonemic clustering. CONCLUSION: The Persian version of the Homophone Meaning Generation Test is an appropriate, valid, and reliable test to evaluate the ability to switch between verbal concepts in the assessment of word-finding performance. PMID- 27390706 TI - Safety and effectiveness assessment of intravenous immunoglobulin in the treatment of relapsing-remitting multiple sclerosis: A meta-analysis. AB - BACKGROUND: Intravenous immunoglobulin (IVIG) is an established treatment of immune mediated demyelinating neuropathy including Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. Recent trials suggest its efficacy in treating relapsing- remitting multiple sclerosis. IVIG exerts a number of effects, which may be beneficial in treating multiple sclerosis (MS): Reduction of inflammation, inhibition of macrophages, and promotion of remyelination. The aim of this study was to provide an overall assessment of the existing trials of safety and effectiveness of IVIG in relapsing- remitting MS compared to other drugs currently available for the treatment of disease activity in MS. METHODS: A systematic search strategy was applied to MEDLINE (PubMed and Ovid Medline (1990- Nov 2014)), Cochrane Library 2014, and Trip Database 2014, CRD. The reference lists from the identified trials, MS clinical handbooks and guidelines for the use of IVIG were studied. This article was conducted without language restrictions. Randomized controlled trials of IVIG in MS were selected. Sixteen double-blinded trails were randomly selected. Ten trials were excluded and we performed a meta-analysis on the six trials (537 participants) of IVIG in comparison to placebo. The methodological quality of the trials was assessed using Jadad checklist. RESULTS: The meta-analysis showed a significant beneficial effect on proportion of relapse-free patients (OR: 1.693; 95% CI-1.205-2.380), on the proportion of patients who improved (OR:2.977; 95% CI 1.769-5.010; p=0.0001) and deteriorated (OR:0.522; 95% CI0.330-0.827; p=0.006) between placebo and IVIG treated patients. In addition, there was a reduction in the annual relapse rate in the IVIG group compared to placebo, which was statistically significant (SMD= 0.218; 95% CI-0.412 to -0.024; p=0.028). The results of the meta-analysis did not show significant differences between Expanded Disability Status Scale (EDSS) changes from baseline (SMD,-0.025; 95% CI,-0.211 to 0.161; p=0.860). CONCLUSION: IVIG can be considered as an alternative therapeutic option, second-line therapy or adjuvant therapy, considering its beneficial effects (high tolerance, need to be injected with longer intervals, etc.) for treating relapsing-remitting MS patients. PMID- 27390707 TI - Manifestations and complications of leptospirosis. PMID- 27390708 TI - Estimation of the prevalence of chronic kidney disease: The results of a model based estimation in Kerman, Iran. AB - BACKGROUND: Chronic kidney disease is asymptomatic until its last stages and though it is increasing globally, we are faced with paucity of a population-based model to assess this disease, particularly in developing countries. Therefore, the aim of this study was to estimate the prevalence and trends of CKD according to a new estimation method. METHODS: Using multiplier method, we estimated the numbers of different stages of CKD based on the number of patients with end stage renal failure from 2006 to 2016. The required multipliers were extracted from a simulation of the disease in Kerman following a dynamic model. The 95% uncertainty interval was computed using Monte-Carlo technique with 10,000 iterations. RESULTS: The prevalence of CKDA (GFR<=90mL/min/1.73m2) and CKDB (GFR less than 60mL/min/1.73m2) patients were estimated to be 7.6% (95% uncertainty interval (UI), 5.7-9.1%) and 1.1% (95% UI, 0.8-1.3%), respectively in 2011. The method revealed that the prevalence may rise up to 25.7% (95% UI, 18.2-32.5%) and 3.7% (95% UI, 2.7-4.5%) for CKDA and CKDB, respectively in 2016, indicating approximately 3.3 times increase for both figures. CONCLUSION: This study predicted an increase in the prevalence of CKD in the future. This may be due to the increasing life expectancy of the population, the increase in the prevalence of non- communicable diseases such as hypertension and diabetes, or patients' survival due to receiving better support. Therefore, the policymakers should be concerned and well informed about this increase. PMID- 27390709 TI - The cost effectiveness of dynamic and static interspinous spacer for lumbar spinal stenosis compared with laminectomy. AB - BACKGROUND: The present study aims to evaluate the cost-effectiveness of Dynamic Interspinous Spacer (Coflex(r)) and Static Spacer (X-STOP (r)) compared to Laminectomy (LAMI) in patients with lumbar spinal stenosis. METHODS: A decision analysis model was developed to estimate the cost-effectiveness. The effectiveness parameters were obtained from a systematic literature review in relevant databases including PUBMED and EMBASE. A meta-analysis was performed using the STATA statistical package and a random model was used to collect measures of mean difference of visual analogue scale (VAS) pain score before and after intervention in X-stop, Coflex and LAMI (95% confidence intervals). Cost data were obtained from provider and associated literature based on health care provider prospective. We assumed that the probability of the success rate of surgery in each intervention from associated literature and calculated Incremental cost effectiveness ratio. A one-way sensitivity analysis was also carried out. RESULTS: Twenty-four out of 294 studies are included in the Meta analysis. The overall pooled estimate of the mean difference of VAS pain score were 3.49 (95% CI 3.7-4.2) and 4.14 (95% CI 3.09- 5.19) for X-stop and Coflex, respectively. In addition, we assumed the overall pooled estimate of 5.3 (95% CI 2.15-7.4) on the basis of literature for LAMI. The average cost per LAMI surgery, X-stop and Coflex was US$ 3019, US$ 2022 and US$ 2566, respectively. Incremental cost effectiveness ratio of X-stop and Coflex versus LAMI was US$ 665.9 and US$ 780.7, respectively. CONCLUSION: Static Interspinous Spacer (X-stop) appears to be the most cost-effective treatment strategy in base case scenario with success rate of LAMI (range between (55%-70%). A sensitivity analysis shows that the increase probability of success rate of LAMI was more than 70 % and less than 55% which lead to the cost effectiveness of the Coflex intervention. PMID- 27390710 TI - A comparison of food pattern, macro- and some micronutrients density of the diet across different socio-economic zones of Tehran. AB - BACKGROUND: The consumption of low quality foods is common in low socioeconomic areas; and according to epidemiological studies, the density of nutrients often proves the quality of diet. This study aimed to compare the density of macronutrients and micronutrients in various parts of Tehran. METHODS: This was a cross-sectional study performed from September to December 2007 in all the 22 districts of the municipality of Tehran including 1,807 households. Experienced interviewers completed a 24-hour recall questionnaire. To estimate the nutrient densities, nutrient intake (grams or milligrams) was calculated per 1,000 kcal energy intake. To calculate the density of energy intake, energy intake (kcal) was divided by 100 g of foodstuff. The 22 districts of Tehran were divided into five zones of north, center, east, west and south. ANOVA and Tukey tests were used. RESULTS: The highest density of protein and fat intake was observed in the north of Tehran, while carbohydrate density was highest in the west, east and south zones, and energy density was highest in the south zone (p<0.05). Calcium and vitamin C had the highest density in the north of Tehran, and vitamin A and riboflavin had the highest density in the north and center of Tehran, and the lowest level in the south of Tehran (p<0.05). CONCLUSION: Despite the high density of energy in the south of Tehran, a deficiency of micronutrient intake was obvious, reflecting the importance of the impact of socioeconomic factors. PMID- 27390711 TI - A comparison between the dimensions of positive transtibial residual limb molds prepared by air pressure casting and weight-bearing casting methods. AB - BACKGROUND: Creating a socket with proper fit is an important factor to ensure the comfort and control of prosthetic devices. Several techniques are commonly used to cast transtibial stumps but their effect on stump shape deformation is not well understood. This study compares the dimensions, circumferences and volumes of the positive casts and also the socket comfort between two casting methods. Our hypothesis was that the casts prepared by air pressure method have less volume and are more comfortable than those prepared by weight bearing method. METHODS: Fifteen transtibial unilateral amputees participated in the study. Two weight bearing and air pressure casting methods were utilized for their residual limbs. The diameters and circumferences of various areas of the residual limbs and positive casts were compared. The volumes of two types of casts were measured by a volumeter and compared. Visual Analogue Scale (VAS) was used to measure the sockets fit comfort. RESULTS: Circumferences at 10 and 15 cm below the patella on the casts were significantly smaller in air pressure casting method compared to the weight bearing method (p=0.00 and 0.01 respectively). The volume of the cast in air pressure method was lower than that of the weight bearing method (p=0.006). The amputees found the fit of the sockets prepared by air pressure method more comfortable than the weight bearing sockets (p=0.015). CONCLUSION: The air pressure casting reduced the circumferences of the distal portion of residual limbs which has more soft tissue and because of its snug fit it provided more comfort for amputees, according to the VAS measurements. PMID- 27390712 TI - Effect of signal to noise ratio on the speech perception ability of older adults. AB - BACKGROUND: Speech perception ability depends on auditory and extra-auditory elements. The signal- to-noise ratio (SNR) is an extra-auditory element that has an effect on the ability to normally follow speech and maintain a conversation. Speech in noise perception difficulty is a common complaint of the elderly. In this study, the importance of SNR magnitude as an extra-auditory effect on speech perception in noise was examined in the elderly. METHODS: The speech perception in noise test (SPIN) was conducted on 25 elderly participants who had bilateral low-mid frequency normal hearing thresholds at three SNRs in the presence of ipsilateral white noise. These participants were selected by available sampling method. Cognitive screening was done using the Persian Mini Mental State Examination (MMSE) test. RESULTS: Independent T- test, ANNOVA and Pearson Correlation Index were used for statistical analysis. There was a significant difference in word discrimination scores at silence and at three SNRs in both ears (p<=0.047). Moreover, there was a significant difference in word discrimination scores for paired SNRs (0 and +5, 0 and +10, and +5 and +10 (p<=0.04)). No significant correlation was found between age and word recognition scores at silence and at three SNRs in both ears (p>=0.386). CONCLUSION: Our results revealed that decreasing the signal level and increasing the competing noise considerably reduced the speech perception ability in normal hearing at low mid thresholds in the elderly. These results support the critical role of SNRs for speech perception ability in the elderly. Furthermore, our results revealed that normal hearing elderly participants required compensatory strategies to maintain normal speech perception in challenging acoustic situations. PMID- 27390713 TI - Gender equity in health: A secondary analysis of data in Iran. AB - BACKGROUND: Gender inequality harms the health of millions of women and girls in all over the world. This study aimed to identify the state of gender equity in the health sector of the Islamic Republic of Iran. METHODS: This study was based on the secondary analysis of the available data in four provinces. The research team held three sessions to select the appropriate indicators for measuring gender equity in Iran. Moreover, using the data of different sources, the indexes were evaluated by applying the brain storming method. To demonstrate the difference between females and males, the ratio of females to males was measured in each indicator. The confidence intervals were used to show significant differences in the gap between men and women. Educational indicators were analyzed using the appraisal framework of UNESCO and International Institute for Education Planning. RESULTS: Findings revealed gender equality in the indicators of education and under-five underweight in all the provinces. However, the indicator of information on the mild psychological diseases showed inequality in favor of males. Infants' mortality, under-five mortality, crude death, drug abuse and smoking showed inequality in favor of females in all the four provinces. The incidence of tuberculosis, severe psychological diseases, and basic and supplementary insurance coverage was equal in all provinces except Tehran. CONCLUSION: This study revealed gender inequality in many indicators among the provinces. Therefore, improving this condition requires policymaking, planning, and conducting appropriate strategies with proper gender approaches. PMID- 27390714 TI - Health technology assessment: Off-site sterilization. AB - BACKGROUND: Every year millions of dollars are expended to equip and maintain the hospital sterilization centers, and our country is not an exception of this matter. According to this, it is important to use more effective technologies and methods in health system in order to reach more effectiveness and saving in costs. This study was conducted with the aim of evaluating the technology of regional sterilization centers. METHODS: This study was done in four steps. At the first step, safety and effectiveness of technology was studied via systematic study of evidence. The next step was done to evaluate the economical aspect of off-site sterilization technology using gathered data from systematic review of the texts which were related to the technology and costs of off-site and in-site hospital sterilization. Third step was conducted to collect experiences of using technology in some selected hospitals around the world. And in the last step different aspects of acceptance and use of this technology in Iran were evaluated. RESULTS: Review of the selected articles indicated that efficacy and effectiveness of this technology is Confirmed. The results also showed that using this method is not economical in Iran. CONCLUSION: According to the revealed evidences and also cost analysis, due to shortage of necessary substructures and economical aspect, installing the off-site sterilization health technology in hospitals is not possible currently. But this method can be used to provide sterilization services for clinics and outpatients centers. PMID- 27390715 TI - Writing qualitative article: It is time to quality improvement. AB - Precis: This debate article highlights some questions from critics of qualitative research. Planning for proper design, philosophical background, researcher as a research instrument in the study, trustworthiness and application of findings are main debates in this field. One of the issues that have been received little attention is report of qualitative inquiry. A qualified report can answer the critics. This requires that the qualitative articles cover all points about the selected method and rigourness of study conduct to convince policy makers, managers and all readers in different level. PMID- 27390716 TI - Is Taurolidine-citrate an effective and cost-effective hemodialysis catheter lock solution? A systematic review and cost- effectiveness analysis. AB - BACKGROUND: Prevention of catheter-related infection is of prime importance,. However, because of the risks caused by the leakage of circulating antibiotics and development of resistance to antibiotics, they are replaced by lock solutions. The aim of this study was to evaluate the efficacy and cost- effectiveness of taurolidine-citrate as a hemodialysis catheter lock solution compared to other common alternatives in Iran. METHODS: To evaluate the efficacy of taurolidine-citrate, a systematic review was conducted by searching electronic databases. The outcomes of interest for cost-effectiveness analysis were as follows: "Catheter-related bacteremia episodes"; "catheter-related bacteremia free survival"; "catheter thrombosis rate" for efficacy evaluation and "reduction of catheter-related infection". For evidence synthesis, a meta-analysis was conducted on the extracted efficacy data. To evaluate the cost of treatments, direct medical costs were included, and the incremental cost-effectiveness ratio was calculated for each comparison. The payers' (patients and insurance companies) perspectives were used for cost analysis. RESULTS: After carrying out the systematic process, three articles were included in the analysis. Considering 95% confidence interval, the relative difference was -0.16 (-0.25 to -0.07) for catheterrelated bacteremia episode, indicating that the rate of catheter-related infections in hemodialysis patients who used taurolidine-citrate was 16% less than in those hemodialysis patients who received heparin. Considering 95% confidence interval, the relative difference was 0.13 (-0.06 0.32) for catheter thrombosis, showing that the rate of catheter-related thrombosis in hemodialysis patients who used taurolidine-citrate was 13% more than in hemodialysis patients who received heparin. The results of this analysis indicated that taurolidine citrate, compared to heparin, was more effective in preventing catheter-related infection; therefore, it could be considered as a superior strategy. Nevertheless, compared to heparin-gentamicin combination, taurolidine-citrate is an inferior strategy because of its higher cost and lower infection prevention. CONCLUSION: Compared to heparin, taurolidine-citrate is a superior option, but it is an inferior strategy compared to heparin-gentamicin combination. The clinical evidences on taurolidine-citrate, heparin and gentamicin/heparin are not sufficient for making confident decisions. PMID- 27390718 TI - Effectiveness of training on preventative nutritional behaviors for type-2 diabetes among the female adolescents: Examination of theory of planned behavior. AB - BACKGROUND: Since type-2 diabetes is the most common chronic disease among Iranian female adolescents, we applied theory of planned behavior to examine the effect of training to intention to preventative nutritional behaviors for type-2 diabetes among female adolescents. METHODS: In this experimental study 200 (11-14 year old) girls from 8 schools of Tehran city (100 in each intervention and control group) were recruited based on cluster sampling method during two stages. For intervention group, an educational program was designed based on the theory of planned behavior and presented in 6 workshop sessions to prevent type-2 diabetes. The data were collected before and two months after the workshops using a valid and reliable (alpha=0.72 and r=0.80) authormade questionnaire based on Ajzens TPB questionnaire manual. The data were analyzed using t-test, chi-square test and analysis of covariance. RESULTS: Findings indicate that the two groups were homogeneous regarding the demographic characteristics before education, but the mean score of the theory components (attitudes, subjective norms, perceived behavioral control, and intention) was higher in the control group. Also, results showed all of the theory components significantly increased after the education in the intervention group (p=0.000). CONCLUSION: Training based on the theory of planned behavior enhances the intention to adherence preventative nutritional behaviors for type-2 diabetes among the studied female adolescents. PMID- 27390717 TI - Health technology assessment of non-invasive interventions for weight loss and body shape in Iran. AB - BACKGROUND: The burden of obesity and diet-related chronic diseases is increasing in Iran, and prevention and treatment strategies are needed to address this problem. The aim of this study was to determine the outcome, cost, safety and cost-consequence of non-invasive weight loss interventions in Iran. METHODS: We performed a systematic review to compare non-invasive interventions (cryolipolysis and radiofrequency/ ultrasonic cavitation) with semi-invasive (lipolysis) and invasive (liposuction). A sensitive electronic searching was done to find available interventional studies. Reduction of abdomen circumference (cm), reduction in fat layer thickness (%) and weight reduction (kg) were outcomes of efficacy. Meta-analysis with random models was used for pooling efficacy estimates among studies with the same follow-up duration. Average cost per intervention was estimated based on the capital, maintenance, staff, consumable and purchase costs. RESULTS: Of 3,111 studies identified in our reviews, 13 studies assessed lipolysis, 10 cryolipolysis and 8 considered radiofrequency. Nine studies with the same follow-up duration in three different outcome group were included in meta-analysis. Radiofrequency showed an overall pooled estimate of 2.7 cm (95% CI; 2.3-3.1) of mean reduction in circumference of abdomen after intervention. Pooled estimate of reduction in fat layer thickness was 78% (95% CI; 73%-83%) after Lipolysis and a pooled estimate of weight loss was 3.01 kg (95% CI; 2.3-3.6) after lipousuction. The cost analysis revealed no significant differences between the costs of these interventions. CONCLUSION: The present study showed that non-invasive interventions appear to have better clinical efficacy, specifically in the body shape measurement, and less cost compared to invasive intervention (liposuction). PMID- 27390719 TI - Impact of vitamin supplements on HAART related hematological abnormalities in HIV infected patients. AB - BACKGROUND: The human immunodeficiency virus (HIV) is one of the most life- threatening human infections. The advent of highly active antiretroviral therapy (HAART) has dramatically changed the course of HIV infection and patients' quality of life. In addition to the benefits, HAART can have numerous side effects and toxicities. Therefore, we aimed to assess the impact of short-term vitamins treatment on hematological parameters of HIV infected patients receiving HAART. METHODS: This cross-sectional study was conducted on 100 confirmed HIV positive patients who referred to Shiraz HIV/AIDS research center in southwest of Iran. The first-line of HAART regimen contained Zidovudine, Lamivudine, and Efavirenz. The studied population received vitamin B12 weekly and folic acid daily for at least one month. RESULTS: After receiving HAART for at least 6 months with adherence above 90%, significant differences (p<0.05) were observed in MCV, MCH, HCT, TLC and RBC status compared to the baseline parameters. After one month of treatment, vitamins in four hematological parameters including TLC, MCV, RBC, and WBC showed significant differences compared to HAART parameters. CONCLUSION: Combined administration of B12 and folate supplements is a beneficial adjuster on hematologic status of HIV infected persons receiving HAART. However, future research with larger studied population and longer follow-up periods is required. Moreover, especial attention should be given to gender because the effect of vitamins was significantly different on some hematologic parameters between different genders. PMID- 27390720 TI - ROLE OF YOGA ON CARDIC AUTONOMIC FUNCTION TESTS AND COGNITION IN TYPE 2 DIABETES. AB - According to International Diabetic Federation, type 2 diabetic population is on the rise globally and cognitive decline is one of the complications seen in type 2 diabetes. The present study is aimed at exploring the role of regular practice of yoga on cognition in type 2 diabetes and also to study the relation between the cognition and functional status of autonomic nervous system by considering the Cardiac Autonomic (CAN) function tests. Ten type 2 diabetic subjects of both the sex, aged between 35-55 years, who practiced yoga for a period of six months at Yogi Vemana Yoga Research Institute were recruited as test group. Age and sex matched ten type 2 diabetic subjects were recruited as control group; both the group subjects are on oral hypoglycemic agents. Glycosylated hemoglobin concentration was estimated with Bio-Rad instrument, cognition was assessed with Addenbrooke's Cognitive Examination Revised battery and Cardiac autonomic function tests were also conducted. Unpaired student t test was performed and p<0.05 is considered statistically significant. The mean HbA1c concentration in control and test group subjects is 7.8+/-1.84 and 6.9+/-0.4% (p=0.03) respectively. Mean cognitive scores in test and control group subjects are 93+/ 4.5 and 85+/-4.0 (p=0.008) respectively. CAN test results didn't showed any significance between the test and control group. But CAN functions are affected in both the groups. Regular practice of yoga in combination with oral hypoglycemic agents has a positive effect on cognition in type 2 diabetes. PMID- 27390721 TI - ROLE OF YOGA IN ALIENATING THE MEMORY DECLINE AND FRONTAL LOBE METABOLITE CHANGES IN TYPE 2 DIABETES. AB - Recent research studies have established the fact, that glycosylation is causing the memory decline and this is further supported by the alteration of brain metabolite concentrations in diabetes. The present study is hypothesized that yoga is having alienating ability of memory decline and alteration of frontal lobe metabolite concentrations, which are the result of glycosylation in type 2 diabetes. Five type 2 diabetic subjects of both the sex, aged between 35-55 years, who practiced yoga over a period of six months in a yoga institute, were recruited as test group. Age and sex matched five type 2 diabetic subjects were recruited as control group, both the group subjects are on oral hypoglycaemic agents. Glycosylated haemoglobin percentage was estimated with Bio-Rad instrument, frontal lobe metabolites were estimated with Proton Magnetic Resonance Spectroscopy (H-MRS), memory was calculated with PGI-Memory Scale (PGIMS) that is a part of PGI-Battery of Brain Dysfunction (PGI-BBD), which is a neuropsychological battery. Mean glycosylated haemoglobin percentage and memory dysfunction rating in control and test group subjects are 6.9+/-0.4 & 7.8+/-1.84 (p=0.03), and 14+/-1& 6+/-1 (p=0.0001) respectively. Right and left frontal lobe N-Acetyl Aspartate (NAA) and Myoionositol (mI) concentrations were more or less similar in both the groups. Yoga is having a significant role in alienating the decline in memory caused by glycosylation in type 2 diabetes but not on the alteration of frontal lobe NAA and mI concentrations. PMID- 27390722 TI - Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats. AB - Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund's adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity. PMID- 27390723 TI - Effect of Layer-by-Layer (LbL) Encapsulation of Nano-Emulsified Fish Oil on Their Digestibility Ex Vivo and Skin Permeability In Vitro. AB - Omega-3 rich fish oils are extremely labile, thus requiring control of oxidation and off flavor development. A recently proposed emulsification method, layer-by layer (LbL) deposition, was found to be a plausible method to enhance the characteristics of bioactive ingredients, especially lipids. The present work was designed to test the possibility of enhancing the uptake and utilization of omega 3 fatty acids present in fish oil. The bioavailability of nano-emulsified fish oil was monitored in terms of intestinal absorption as well as skin permeability by using the everted intestinal sac model and Franz cell model. The skin permeability and intestinal absorption characteristics was significantly improved by LbL emulsification with lecithin/chitosan/low methoxypectin. Multilayer encapsulation along with nano-emulsification can be a useful method to deliver biologically active lipids and related components, such as fish oil. The protective effect of this tool from lipid oxidation still needs to be verified. PMID- 27390724 TI - Changes in Nutrient Composition, Antioxidant Properties, and Enzymes Activities of Snake Tomato (Trichosanthes cucumerina) during Ripening. AB - Snake tomato (Trichosanthes cucumerina) has been cultivated and used as a replacement for Lycopersicum esculentum in many Asian and African diets. Matured T. cucumerina fruits were harvested at different ripening stages and separated into coats and pulps for analyses to determine their suitability for use in culinary. They were analyzed for the nutritional composition and antioxidant potential using different biochemical assays [1,1-diphenyl-2-picrylhydrazyl, 2,2' azinobis( 3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities, and ferric reducing antioxidant power] and antioxidative enzymes activities. The nutritional composition revealed that T. cucumerina contains over 80% water and is very rich in fiber, thus it can serve as a good natural laxative. The lycopene and beta-carotene contents were especially high in the ripe pulp with values of 21.62+/-1.22 and 3.96+/-0.14 mg/100 g, respectively. The ascorbic acid content was highest in the pulp of unripe fruit with a value of 56.58+/-1.08 mg/100 g and significantly (P<0.05) decreased as ripening progressed. The antioxidant potential of the fruits for the 3 assays showed that unripe pulp> ripe coat> ripe pulp> unripe coat. There were decreases in the antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, and glutathione reductase) activities, with the exception of catalase, as ripening progressed in the fruits. These decreased activities may lead to the softening of the fruit during ripening. Harnessing the antioxidative potential of T. cucumerina in culinary through consumption of the coats and pulps will alleviate food insecurity and help maintain good health among many dwellers in sub-Saharan Africa and Southeast Asia. PMID- 27390725 TI - Determination of Optimal Harvest Time of Chuchung Variety Green Rice((r)) (Oryza sativa L.) with High Contents of GABA, gamma-Oryzanol, and alpha-Tocopherol. AB - In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice((r)) (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as gamma-aminobutyric acid, gamma-oryzanol, and alpha-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products. PMID- 27390726 TI - Association between Dietary Acid Load and Insulin Resistance: Tehran Lipid and Glucose Study. AB - In the current study, we investigated the longitudinal association between dietary acid load and the risk of insulin resistance (IR) in the Tehranian adult population. This longitudinal study was conducted on 925 participants, aged 22~80 years old, in the framework of the third (2006~2008) and fourth (2009~2011) phases of the Tehran Lipid and Glucose Study. At baseline, the dietary intake of subjects was assessed using a validated semi-quantitative food frequency questionnaire, and the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated at baseline. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up; IR was defined according to optimal cut-off values. Multiple logistic regression models were used to estimate the risk of IR according to the PRAL and NEAP quartile categories. Mean age and body mass index of the participants were 40.3 years old of 26.4 kg/m(2), respectively. Mean PRAL and NEAP scores were -11.2 and 35.6 mEq/d, respectively. After adjustment for potential confounders, compared to the lowest quartile of PRAL and NEAP, the highest quartile was accompanied with increased risk of IR [odds ratio (OR)=2.81, 95% confidence interval (CI)=1.32~5.97 and OR=2.18, 95% CI=1.03 ~4.61, respectively]. Our findings suggest that higher acidic dietary acid-base load, defined by higher PRAL and NEAP scores, may be a risk factor for the development of IR and related metabolic disorders. PMID- 27390727 TI - Antioxidant Contents and Antioxidant Activities of White and Colored Potatoes (Solanum tuberosum L.). AB - This study was performed to evaluate and compare the antioxidant substance content and antioxidant activities of white (Superior) and colored (Hongyoung, Jayoung, Jasim, Seohong, and Jaseo) potatoes. The potatoes were extracted with 80% ethanol and were evaluated for the total polyphenol, flavonoid, and anthocyanin contents and for 1,1-diphenyl- 2-picrylhydrazyl (DPPH)/2,2'-azino bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity, reducing power, and ferrous metal ion chelating effect. The total polyphenol, flavonoid, and anthocyanin contents of Hongyoung and Jayoung were higher than white and other colored potatoes. All colored potato extracts, except for Jaseo and Seohong, showed higher ABTS radical scavenging activities than the general white potato extract. Hongyoung and Jayoung had the highest ABTS and DPPH radical scavenging activities. Optical density values for the reducing power of Jayoung and Jaseo at concentration of 2 mg/mL were 0.148 and 0.090, respectively. All colored potato extracts had lower ferrous metal ion chelating effect than the white potato. A significant (P<0.05) positive correlation was observed between total polyphenol content and total flavonoid content (r=0.919), anthocyanin content (r=0.992), and ABTS radical scavenging activity (r=0.897). Based on these results, this research may be useful in developing the Hongyoung and Jayoung cultivars with high antioxidant activities. PMID- 27390728 TI - Aglycone Isoflavones and Exopolysaccharides Produced by Lactobacillus acidophilus in Fermented Soybean Paste. AB - Bioconversion of aglycone-formed isoflavones from glycoside-formed isoflavones by commercial lactic acid bacteria in fermented soybean paste was evaluated. Enterococcus faecium KCTC 13410 showed the most resistant capacity and Lactobacillus acidophilus KCTC 3925 had a sensitive susceptibility at a high NaCl concentration (13.2%) in fermented soybean paste. Among the 5 strains tested, Lac. acidophilus KCTC 3925 showed the highest relative ratio of aglycone-formed isoflavones to total isoflavones in fermented soybean paste. Production of exopolysaccarides (EPS) by lactic acid bacteria was compared using de Man, Rogosa, and Sharpe medium containing 1% sucrose at 37 degrees C for 48 h. Among the 5 lactic acid bacteria, Lac. acidophilus KCTC 3925 and Lactobacillus rhamnosus KCTC 3929 were investigated to produce EPS. Based on the results concerning growing susceptibility and conversion of aglycone-formed isoflavones/EPS production, it is anticipated that Lac. acidophilus KCTC 3925 may be used for preparation of Cheonggukjang, which contains relative low NaCl content. PMID- 27390729 TI - Isolation and Structural Characterization of an Oligosaccharide Produced by Bacillus subtilis in a Maltose-Containing Medium. AB - Among 116 bacterial strains isolated from Korean fermented foods, one strain (SS 76) was selected for producing new oligosaccharides in a basal medium containing maltose as the sole source of carbon. Upon morphological characterization using scanning electron microscopy, the cells of strain SS-76 appeared rod-shaped; subsequent 16S rRNA gene sequence analysis revealed that strain SS-76 was phylogenetically close to Bacillus subtilis. The main oligosaccharide fraction B extracted from the culture supernatant of B. subtilis SS-76 was purified by high performance liquid chromatography. Subsequent structural analysis revealed that this oligosaccharide consisted only of glucose, and methylation analysis indicated similar proportions of glucopyranosides in the 6-linkage, 4-linkage, and non-reducing terminal positions. Matrix-assisted laser-induced/ionization time-of-flight/mass spectrometry and electrospray ionization-based liquid chromatography-mass spectrometry/mass spectrometry analyses suggested that this oligosaccharide consisted of a trisaccharide unit with 1,6- and 1,4-glycosidic linkages. The anomeric signals in the (1)H-nuclear magnetic resonance spectrum corresponded to alpha-anomeric configurations, and the trisaccharide was finally identified as panose (alpha-D-glucopyranosyl-1,6-alpha-D-glucopyranosyl-1,4-D glucose). These results suggest that B. subtilis SS-76 converts maltose into panose; strain SS-76 may thus find industrial application in the production of panose. PMID- 27390730 TI - Enhanced Production of Phenolic Compounds from Pumpkin Leaves by Subcritical Water Hydrolysis. AB - Enhanced production of individual phenolic compounds by subcritical water hydrolysis (SWH) of pumpkin leaves was investigated at various temperatures ranging from 100 to 220 degrees C at 20 min and at various reaction times ranging from 10 to 50 min at 160 degrees C. Caffeic acid, p-coumaric acid, ferulic acid, and gentisic acid were the major phenolic compounds in the hydrolysate of pumpkin leaves. All phenolic compounds except gentisic acid showed the highest yield at 160 degrees C, but gentisic acid showed the highest yield at 180 degrees C. The cumulative amount of individual phenolic compounds gradually increased by 48.1, 52.2, and 78.4 MUg/g dry matter at 100 degrees C, 120 degrees C, and 140 degrees C, respectively, and then greatly increased by 1,477.1 MUg/g dry matter at 160 degrees C. The yields of caffeic acid and ferulic acid showed peaks at 20 min, while those of cinnamic acid, p-coumaric acid, p-hydroxybenzoic acid, and procatechuic acid showed peaks at 30 min. Antioxidant activities such as 2,2 diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power values gradually increased with hydrolysis temperature and ranged from 6.77 to 12.42 mg ascorbic acid equivalents/g dry matter and from 4.25 to 8.92 mmol Fe(2+)/100 g dry matter, respectively. Color L* and b* values gradually decreased as hydrolysis temperature increased from 100 degrees C to 140 degrees C. At high temperatures (160 degrees C to 220 degrees C), L* and b* values decreased suddenly. The a* value peaked at 160 degrees C and then decreased as temperature increased from 160 degrees C to 220 degrees C. These results suggest that SWH of pumpkin leaves was strongly influenced by hydrolysis temperature and may enhanced the production of phenolic compounds and antioxidant activities. PMID- 27390731 TI - Optimization of Extraction of Cycloalliin from Garlic (Allium sativum L.) by Using Principal Components Analysis. AB - In this study, we report the optimal extraction conditions for obtaining organosulfur compounds, such as cycloalliin, from garlic by using principal component analysis (PCA). Extraction variables including temperature (40~80 degrees C), time (0.5~12 h), and pH (4~12) were investigated for the highest cycloalliin yields. The cycloalliin yield (5.5 mmol/mL) at pH 10 was enhanced by ~40% relative to those (~3.9 mmol/mL) at pH 4 and pH 6. The cycloalliin level at 80 degrees C showed the highest yield among the tested temperatures (5.05 mmol/mL). Prolonged extraction times also increased cycloalliin yield; the yield after 12 h was enhanced ~2-fold (4 mmol/mL) compared to the control. Isoalliin and cycloalliin levels were inversely correlated, whereas a direct correlation between polyphenol and cycloalliin levels was observed. In storage for 30 days, garlic stored at 60 degrees C (11 mmol/mL) showed higher levels of cycloalliin and polyphenols than those at 40 degrees C, with the maximum cycloalliin level (13 mmol/mL) on day 15. Based on the PCA analysis, the isoalliin level depended on the extraction time, while cycloalliin amounts were influenced not only by extraction time, but also by pH and temperature. Taken together, extraction of garlic at 80 degrees C, with an incubation time of 12 h, at pH 10 afforded the maximum yield of cycloalliin. PMID- 27390732 TI - Effects of a Pre-Filter and Electrolysis Systems on the Reuse of Brine in the Chinese Cabbage Salting Process. AB - In this study, the effects of a pre-filter system and electrolysis system on the safe and efficient reuse of brine in the cabbage salting process were investigated. First, sediment filter-electrolyzed brine (SF-EB) was selected as brine for reuse. Then, we evaluated the quality and microbiological properties of SF-EB and Chinese cabbage salted with SF-EB. The salinity (9.4%) and pH (4.63) of SF-EB were similar to those of control brine (CB). SF-EB turbidity was decreased (from 0.112 to 0.062) and SF-EB residual chlorine (15.86 ppm) was higher than CB residual chlorine (0.31 ppm), and bacteria were not detected. Salinity (2.0%), pH (6.21), residual chlorine (0.39 ppm), chromaticity, hardness, and chewiness of cabbage salted with SF-EB were similar to those of cabbage salted with CB. The total bacterial count in cabbage salted with CB was increased as the number of reuses increased (from 6.55 to 8.30 log CFU/g), whereas bacteria in cabbage salted with SF-EB was decreased (from 6.55 to 5.21 log CFU/g). These results show that SF-EB improved the reusability of brine by removing contaminated materials and by sterilization. PMID- 27390733 TI - Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in alpha-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells. AB - Previous research showed that resveratrol (trans-3,4',5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4',5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans 3,5-dimethoxy-4'-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on alpha-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in alpha-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 MUM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of alpha MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in alpha-MSH-triggered B16/F10 murine melanoma cells. PMID- 27390734 TI - Influence of Sulfur Fertilization on the Antioxidant Activities of Onion Juices Prepared by Thermal Treatment. AB - Two onions (Sulfur-1 and Sulfur-4) cultivated with different sulfur applications were thermally processed to elucidate the effects of heat treatment on browning index and antioxidant activity. Sulfur-4 onion had higher sulfur content compared with the Sulfur-1 onion. After thermal processing, browning intensity was different between the two onions juices, with lower values observed for Sulfur-4 onion juice. This suggests that sulfur inhibits the Maillard browning reaction. The total reducing capacity of the juices increased at higher thermal processing temperatures; however, it was also lower in the Sulfur-4 onion juice. This suggests that the heat treatment of onions enhanced their antioxidant activity, but the effect was offset in the Sulfur-4 onion juice presumably due to higher sulfur content. This study indicates that sulfur, a core element for the functionality of onions, can decrease the antioxidant activity of thermally processed onions because of its potential as a Maillard reaction inhibitor. PMID- 27390735 TI - Nano-mechanical Phenotype as a Promising Biomarker to Evaluate Cancer Development, Progression, and Anti-cancer Drug Efficacy. AB - Since various bio-mechanical assays have been introduced for studying mechanical properties of biological samples, much progress has been made in cancer biology. It has been noted that enhanced mechanical deformability can be used as a marker for cancer diagnosis. The relation between mechanical compliances and the metastatic potential of cancer cells has been suggested to be a promising prognostic marker. Although it is yet to be conclusive about its clinical application due to the complexity in the tissue integrity, the nano-mechanical compliance of human cell samples has been evaluated by several groups as a promising marker in diagnosing cancer development and anticipating its progression. In this review, we address the mechanical properties of diverse cancer cells obtained by atomic force microscopy-based indentation experiments and reiterate prognostic relations between the nano-mechanical compliance and cancer progression. We also review the nano-mechanical responses of cancer cells to the anti-cancer drug treatment in order to interrogate a possible use of nano mechanical compliance as a means to evaluate the effectiveness of anti-cancer drugs. PMID- 27390736 TI - Chrysophanic Acid Induces Necrosis but not Necroptosis in Human Renal Cell Carcinoma Caki-2 Cells. AB - BACKGROUND: Chrysophanic acid, also known as chrysophanol, has a number of biological activities. It enhances memory and learning abilities, raises superoxide dismutase activity, and has anti-cancer effects in several model systems. According to previous reports, chrysophanic acid-induced cell death shares features of necrotic cell death. However, the molecular and cellular processes underlying chrysophanic acid-induced cell death remain poorly understood. METHODS: Chrysophanic acid-induced cell death was monitored by cell viability assay and Annexin V-propidium iodide (PI) staining of renal cell carcinoma Caki-2 cells. The induction of intracellular reactive oxygen species (ROS) by chrysophanic acid and the suppression of ROS by anti-oxidants were evaluated by 2',7'-dichlorofluorescin diacetate staining. The expression and phosphorylation of proteins that are involved in apoptosis and necroptosis were detected by immunoblotting. RESULTS: The extent of chrysophanic acid-induced cell death was concentration and time dependent, and dead cells mainly appeared in the PI-positive population, which is a major feature of necrosis, upon fluorescence activated cell sorting analysis. Chrysophanic acid-induced cell death was associated with the generation of intracellular ROS, and this effect was reversed by pretreatment with N-acetyl cysteine. Chrysophanic acid-induced cell death was not associated with changes in apoptotic or necroptotic marker proteins. CONCLUSIONS: The cell death induced by chrysophanic acid resembled neither apoptotic nor necroptotic cell death in human renal cell carcinoma Caki-2 cells. PMID- 27390737 TI - The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts. AB - BACKGROUND: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. METHODS: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. RESULTS: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor beta1-induced migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. CONCLUSIONS: The extracts of F. koreana may possess the potential to inhibit the breast cancer induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts. PMID- 27390738 TI - High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity. AB - BACKGROUND: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in Apc(Min/+) mice. METHODS: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. RESULTS: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2' deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). CONCLUSIONS: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis. PMID- 27390739 TI - Human Papillomavirus Prevalence and Type Distribution Among 968 Women in South Korea. AB - BACKGROUND: Geographic variation in the prevalence of carcinogenic types and human papillomavirus (HPV) genotype distribution is closely associated with the impact of HPV prophylactic vaccines. We determined the prevalence and distribution of HPV genotypes among healthy women in Korea. METHODS: This study included 968 healthy women who were examined at a health promotion center of the Korea University Guro Hospital between January and June 2013. Each participant had a Pap test and a HPV DNA test using the AnyplexTM II HPV 28 Detection system, which detects 19 high-risk HPVs (HR HPVs) and 9 low-risk HPVs (LR HPVs). Women with abnormal cytology and/or positivity for HR HPVs were referred to colposcopic biopsy. RESULTS: Overall HR HPV prevalence based on the assay was 33.7%. Among them, 225 women had single infection and 101 women had multiple infection. The most frequently occurring HR HPV types were 53 (6.5%), 52 (6.1%), 58 (4.8%), 16 (4.5%), and 68 (4.2%). The most frequently occurring LR HPV types were 54 (5.4%), 70 (3.8%), 42 (3.6%), 61 (3.4%), and 44 (3.1%). The prevalence of HPV 16 was highest (17.6%) among women with cervical intraepithelial neoplasia (CIN) and HPV 16 was strongly associated with a diagnosis of CIN2/3 (odds ratio = 20.5; 95% confidence interval: 3.9-107.1; P < 0.0001). CONCLUSIONS: HPV 53, 52, 58, 16, and 68 were common HR HPV types among healthy Korean women. HPV16 was the most common type in high-grade CIN lesions, as shown in most studies worldwide. The results might be useful information for cervical cancer prevention in South Korea. PMID- 27390740 TI - Suppression of beta-catenin Signaling Pathway in Human Prostate Cancer PC3 Cells by Delphinidin. AB - Delphinidin possesses strong anti-oxidant, anti-inflammatory, and anti-cancer properties. Suppression of the Wnt/beta-catenin signaling pathway is a potential strategy for chemoprevention and therapy. As aberrant activation of the beta catenin signaling pathway contributes to prostate cancer progression, we evaluated the effect of delphinidin on this pathway in human PC3 prostate cancer cells. An MTT assay showed that treatment with delphinidin (15-180 MUM, 72 hours) resulted in a dose-dependent growth inhibition of cells. Treatment with delphinidin increased the phosphorylation of serine or threonine residues on beta catenin and decreased the levels of cytoplasmic beta-catenin. Moreover, treatment with delphinidin inhibited the nuclear translocation of beta-catenin and the expression of beta-catenin target genes such as cyclin D1, c-myc, Axin-2, and T cell factor-1. Delphinidin also induced the phosphorylation of glycogen synthase kinase 3beta and the expression of adenomatous polyposis coli and Axin proteins. Our results indicate that inhibition of cell growth by delphinidin is mediated, at least in part, through modulation of the beta-catenin signaling pathway. We suggest that delphinidin is a potent inhibitor of Wnt/beta-catenin signaling in prostate cancer cells. PMID- 27390741 TI - A Multi-stage Carcinogenesis Model to Investigate Caloric Restriction as a Potential Tool for Post-irradiation Mitigation of Cancer Risk. AB - The risk of radiation-induced cancer adds to anxiety in low-dose exposed populations. Safe and effective lifestyle changes which can help mitigate excess cancer risk might provide exposed individuals the opportunity to pro-actively reduce their cancer risk, and improve mental health and well-being. Here, we applied a mathematical multi-stage carcinogenesis model to the mouse lifespan data using adult-onset caloric restriction following irradiation in early life. We re-evaluated autopsy records with a veterinary pathologist to determine which tumors were the probable causes of death in order to calculate age-specific mortality. The model revealed that in both irradiated and unirradiated mice, caloric restriction reduced the age-specific mortality of all solid tumors and hepatocellular carcinomas across most of the lifespan, with the mortality rate dependent more on age owing to an increase in the number of predicted rate limiting steps. Conversely, irradiation did not significantly alter the number of steps, but did increase the overall transition rate between the steps. We show that the extent of the protective effect of caloric restriction is independent of the induction of cancer from radiation exposure, and discuss future avenues of research to explore the utility of caloric restriction as an example of a potential post-irradiation mitigation strategy. PMID- 27390742 TI - Human Papillomavirus Genotyping and p16(INK4a) Expression in Cervical Lesions: A Combined Test to Avoid Cervical Cancer Progression. AB - Cervical cancer is a major public health problem in Morocco. The cervical cancer has a long precancerous period that provides an opportunity for the screening and treatment. Improving screening tests is a priority goal for the early diagnosis of cervical cancer. This study was conducted to evaluate the combination of p16(INK4a) protein expression, human papillomavirus (HPV) typing, and histopathology for the identification of cervical lesions with high risk to progress to cervical cancer among Moroccan women. A total of 96 cervical biopsies were included in this study. Signal amplification in situ hybridization with biotinylated probes was used to detect HPV. Immunohistochemistry was used to evaluate the expression of p16(INK4a) protein. HPV DNA was detected in 74.0% of the biopsies (71/96). Of the seventy-one positive HPV cases, we detected 67.6% (48/71) of high risk (HR)-HPV (HPV 16 and 18), 24% of low risk-HPV (HPV 6 and 11), 1.4% intermediate risk-HPV (HPV 31, 33, and 35), and 7% coinfections (HPV 6/11 and 16/18). Overexpression of p16(INK4a) protein was observed in 72.9% (70/96) of the biopsies. In addition, p16(INK4a) protein detection was closely correlated with recovery of HR HPV. Our result showed that p16(INK4a) expression level is correlated with HR-HPV status. PMID- 27390743 TI - Primary Acquired Melanosis: Clinical, Histopathologic and Optical Coherence Tomographic Correlation. AB - AIM: To assess the use of anterior segment optical coherence tomography (OCT) as an adjuvant diagnostic tool in primary acquired melanosis (PAM) by correlating clinical, histopathologic and anterior segment OCT findings. METHODS: Twenty-four patients (24 eyes) with PAM of the conjunctiva, cornea or both were imaged with an anterior segment OCT device (RTVue, model-RT100; Optovue Inc., Fremont, Calif., USA). RESULTS: Histopathologic diagnosis following excisional or incisional biopsy was confirmed in 13 out of 24 patients (54.6%). OCT images showed a characteristic uniformly thick basal epithelial hyperreflective band (about 20 MUm thick) and normal thickness of the overlying epithelial layer in all patients (100%). The hyperreflective band on OCT correlated with the basal epithelial melanocytic pigmentation noted on histopathologic examination but did not vary in thickness between cases with or without atypia. CONCLUSIONS: The characteristic basal epithelial hyperreflective band with normal overlying epithelium in the absence of cysts observed in all cases by anterior segment OCT correlated with clinical and histopathologic features of conjunctival and corneal PAM. Anterior segment OCT may be helpful as a noninvasive diagnostic tool for PAM. Improvement in resolution is necessary to detect melanocytic hyperplasia and aytpia suggestive of malignant potential. PMID- 27390744 TI - Phospholipase A2 Receptor-Positive Idiopathic Membranous Glomerulonephritis with Onset at 95 Years: Case Report. AB - A 95-year-old woman was admitted to our hospital for evaluation of bilateral lower-limb edema persisting for 3 months. Serum creatinine was 1.55 mg/dl, and urinary protein excretion was 9.1 g/day. Renal biopsy revealed stage 1 membranous glomerulonephritis (MGN) with immunoglobulin G4-dominant staining. This patient did not have any underlying disease such as infection with hepatitis B or C virus or malignancy, and anti-phospholipase A2 receptor (PLA2R) antibody was detected in the serum. Accordingly, idiopathic MGN was diagnosed. Corticosteroid therapy was avoided, but hemodialysis was required to treat generalized edema. The patient is currently doing well. This is the oldest reported case of idiopathic MGN with positivity for anti-PLA2R antibody. PMID- 27390745 TI - Towards research-tested smartphone applications for preventing breast cancer. AB - Efforts to prevent breast cancer and other chronic illnesses have focused on promoting physical activity, healthy diet and nutrition, and avoidance of excessive alcohol consumption. Smartphone applications (apps) offer a low-cost, effective strategy for breast cancer prevention in women through behavioral change. However, there are currently no research-tested smartphone apps for breast cancer prevention that are suitable for women with varying levels of health literacy and eHealth literacy. In this perspective, we consider modifiable risk factors for breast cancer in women in relation to the development of smartphone apps to promote healthy behaviors associated with breast cancer-risk reduction. First, we provide a summary of breast cancer risk factors that are modifiable through behavioral change including their corresponding relative risk. Second, we discuss scientific issues related to the development of smartphone apps for the primary prevention of breast cancer and offer suggestions for further research. Smartphone apps for preventing breast cancer should be tailored for women at different life stages (e.g., young women, women who are post menopausal, and older women). Topics such as breastfeeding and oral contraceptives are appropriate for younger women. Weight management, physical activity, avoiding cigarette smoking, and dispelling breast cancer myths are appropriate for women of all ages. As women age, topics such as hormone replacement therapy or comorbid health conditions become more important to address. Apps for breast cancer prevention should be grounded in a behavioral theory or framework and should be suitable for people with varying levels of health literacy. Future developments in smartphone apps for breast cancer prevention should include apps that are tailored for specific cultural, racial, and ethnic groups. PMID- 27390746 TI - The Chronobiology of Stanford Type A Aortic Dissections: A Comparison of Northern versus Southern Hemispheres. AB - BACKGROUND: Seasonal variations of Stanford Type A dissections (STADs) have been previously described in the Northern Hemisphere (NH). This study sought to determine if these variation are mirrored in the Southern Hemisphere (SH). METHODS: Data from patients treated surgically for STADs were retrospectively obtained from existing administrative and clinical databases from NH and SH sites. Data points of interest included age, sex, date of dissection, and 30-day mortality. The dates of dissections (independent of year) were then organized by season. RESULTS: A total of 1418 patients were identified (729 NH and 689 SH) with complete data available for 1415; 896 patients were male with a mean age was 61 +/- 14 years, and the overall 30-day mortality was 17.3%. Comparison of NH and SH on a month-to-month basis demonstrated a 6-month phase shift and a significant difference by season, with STADs occurring predominantly in the winter and least in the summer. Decomposition of the monthly incidence using Fourier analysis revealed the phase shift of the primary harmonic to be -21.9 and 169.8 degrees (days), respectively, for NH and SH. The resultant 191.7 day difference did not exactly correspond to the anticipated 6-month difference but was compatible with the original hypothesis. CONCLUSION: Chronobiology plays a role in the occurrence of STADs with the highest occurrence in the winter months independent of the hemisphere. Season is not the predominant reason why aortas dissect, but for patients at risk, the increase in systemic vascular resistance during the winter months may account for the seasonal variations seen. PMID- 27390747 TI - Quadricuspid Aortic Valve Combined with Moderate Ascending Aortic Dilatation: A Report of Four Cases. AB - The quadricuspid aortic valve is a very uncommon malformation associated with aortic insufficiency, aortic stenosis, endocarditis, and ascending aortic dilatation. We report four cases of this aortic valve malformation. One patient with severe aortic regurgitation and moderate aortic dilatation required aortic valve replacement. Three patients had mild or moderate aortic insufficiency combined with moderate ascending aortic dilatation. These patients were referred to follow-up. The presented cases demonstrate that this aortic valve malformation may not be as rare as it appears and that attention must be paid to any quadricuspid findings during computed tomographic angiography and echocardiography. PMID- 27390748 TI - Principles for Management of Intraoperative Acute Type A Aortic Dissection. AB - Intraoperative Type A aortic dissection is a rare pathology with incidence of 0.06-0.32%. It is associated with a high mortality between 30-50%. Some associated risk factors, including hypertension, enlarged aorta, peripheral vascular disease, advanced age, atheroma, and high arterial pressure on cardiopulmonary bypass, have been identified. Modification of these risk factors could reduce the incidence of this event. Prompt diagnosis and management, with the aid of intraoperative trans-esophageal echocardiography and/or epi-aortic ultrasound has been shown to reduce the mortality to 17%. We illustrate the principles of management of this pathology with the case of a 62-year-old female who developed acute Type A aortic dissection while undergoing minimally invasive mitral valve repair. PMID- 27390749 TI - Complex Reoperation for Late Complications After Acute Type A Aortic Dissection Surgery. AB - The correct management of acute Type A dissection continues to be a challenge. The primary goal is to save the patient's life. However, the decision regarding the surgical approach determines possible later complications. We present the case of a 59-year-old female patient with a past history of emergent surgery for acute Type A dissection treated by supracoronary ascending and aortic valve replacement 19 years previously. Later, in a second endovascular approach, the descending aorta was treated by a thoracic endoprosthesis. During follow-up a dilated aortic root and a Type I endoleak were observed, and complex reoperation was required. We performed a total aortic arch replacement with a 4-branched graft and a complete aortic root replacement using the Cabrol technique for the reinsertion of the coronary arteries. The mechanical aortic normally functioning valve was preserved. The patient was discharged 30 days postoperatively. PMID- 27390750 TI - Successive Stages of Mycotic Aortic Arch Aneurysm Development. AB - An 81-year-old male presented with an abscessed tumor of the cecum and complicated by a mycotic aneurysm of the aortic arch. We present successive stages of mycotic aneurysm development as seen on serial computerized tomography scans. PMID- 27390751 TI - List of Upcoming Meetings. PMID- 27390752 TI - Trace Amine-Associated Receptor Type 1 as A Target for The Development of Treatments for Stimulant Abuse. PMID- 27390753 TI - Differential Roles for Dopamine D1-Like and D2-Like Receptors in Mediating the Reinforcing Effects of Cocaine: Convergent Evidence from Pharmacological and Genetic Studies. AB - A series of studies by Drs. Barak Caine, James Woods, Gregory Collins, Jonathan Katz and Takato Hiranita demonstrated a novel and unique reinforcing effect using dopamine (DA) D2-like receptor [D2-like R: D2, D3, and D4 receptor subtypes (respectively, D2R, D3R, and D4R)] agonists in rats and genetically modified mice. In order to understand how important their findings are, a comparison was made regarding the reinforcing effects of DA D2-like R full agonists with those of DA uptake inhibitors and of a DA D1-like receptor [D1-like R, D1 and D5 receptor subtypes (D1R and D5R)] full agonist (+/-)-SKF 82958. PMID- 27390754 TI - Detection of Hydrogen Peroxide by DAB Staining in Arabidopsis Leaves. AB - In this protocol, the in situ detection of hydrogen peroxide (one of several reactive oxygen species) is described in mature Arabidopsis rosette leaves by staining with 3,3'-diaminobenzidine (DAB) using an adaptation of previous methods (Thordal-Christensen et al., 1997; Bindschedler et al., 2006; Daudi et al., 2012). DAB is oxidized by hydrogen peroxide in the presence of some haem containing proteins, such as peroxidases, to generate a dark brown precipitate. This precipitate is exploited as a stain to detect the presence and distribution of hydrogen peroxide in plant cells. The protocol can be modified slightly to detect hydrogen peroxide in different types of plant tissue. PMID- 27390755 TI - Bronchoalveolar Lavage and Lung Tissue Digestion. AB - Bronchoalveolar lavage (BAL) is a simple but valuable and typically performed technique commonly used for studying the pathogenesis of lung diseases such as asthma and COPD. Cell counts can be combined with new methods for examining inflammatory responses, such as ELISA, Flow cytometric analysis, immunohistochemistry, quantitative polymerase chain reaction, and HPLC to assess cellular expression for inflammatory cytokines and growth factor. Here we describe a basic procedure to collect BAL fluid and digest lung tissue for assessing a number of pulmonary components. PMID- 27390756 TI - Bimolecular Fluorescence Complementation (BiFC) Assay for Direct Visualization of Protein-Protein Interaction in vivo. AB - Bimolecular Fluorescence Complementation (BiFC) assay is a method used to directly visualize protein-protein interaction in vivo using live-cell imaging or fixed cells. This protocol described here is based on our recent paper describing the functional association of human chromatin adaptor and transcription cofactor Brd4 with p53 tumor suppressor protein (Wu et al., 2013). BiFC was first described by Hu et al. (2002) using two non-fluorescent protein fragments of enhanced yellow fluorescent protein (EYFP), which is an Aequorea victoria GFP variant protein, fused respectively to a Rel family protein and a bZIP family transcription factor to investigate interactions between these two family members in living cells. The YFP was later improved by introducing mutations to reduce its sensitivity to pH and chloride ions, thus generating a super-enhanced YFP, named Venus fluorescent protein, without showing diminished fluorescence at 37 degrees C as typically observed with EYFP (Nagai et al., 2006). The fluorescence signal is regenerated by complementation of two non-fluorescent fragments (e.g., the Venus N-terminal 1-158 amino acid residues, called Venus-N, and its C terminal 159-239 amino acid residues, named Venus-C; see Figure 1A and Gully et al., 2012; Ding et al., 2006; Kerppola, 2006) that are brought together by interaction between their respective fusion partners (e.g., Venus-N to p53, and Venus-C to the PDID domain of human Brd4; see Figure 1B and 1C). The intensity and cellular location of the regenerated fluorescence signals can be detected by fluorescence microscope. The advantages of the proximity-based BiFC assay are: first, it allows a direct visualization of spatial and temporal interaction between two partner proteins in vivo; second, the fluorescence signal provides a sensitive readout for detecting protein-protein interaction even at a low expression level comparable to that of the endogenous proteins; third, the intensity of the fluorescence signal is proportional to the strength of protein protein interaction (Morell et al., 2008); and fourth, the BiFC signals are derived from intrinsic protein-protein interaction, rather than from extrinsic fluorophores that may not reflect true protein-protein interaction due to their nonspecific association with cellular macromolecules or subcellular compartments. However, some limitations of BiFC include slow maturation (T1/2 ~ 1 h) of an eventually stable BiFC complex (Hu et al., 2002), making it unsuitable for real time observation of transient interaction that disappears prior to BiFC detection, and enhanced BiFC background at high expression levels due to fusion independent association between two non-fluorescent fragments association. BiFC signals generated by in vivo protein-protein interaction can be validated by amino acid mutation introduced at the protein-protein contact surfaces. This imaging technique has been widely used in different cell types and organisms (Kerppola, 2006). PMID- 27390757 TI - Dissection of Different Areas from Mouse Hippocampus. AB - The hippocampus modulates a number of modules including memory consolidation, spatial navigation, temporal processing and emotion. A banana-shaped structure, the hippocampus is constituted of morphologically distinct subregions including the dentate gyrus, CA3 and CA1 (here, we do not distinguish the "hippocampus proper" which consists only of CA1, CA3 and smaller CA2 and CA4 areas, from the "hippocampal formation," composed of these in addition to the dentate gyrus and subiculum). Distinct cell types give rise to unique axonal fiber pathways in the dentate gyrus, CA3 and CA1 subregions; accordingly, these areas may exhibit differential molecular profiles in response to a number of behavioral paradigms and pharmacological and genetic treatments. It is therefore in the interest of the investigator to dissect a specific subregion from the whole hippocampus. Here we outline a protocol for subregion-specific dissection from the adult mouse. PMID- 27390758 TI - Measurement of Acetylcholine from Cell Lines. AB - Cigarette smoking is the leading risk factor for the development of lung cancer. It is estimated that smoking is associated with 80-90% of lung cancer cases throughout the world (see References 1 and 2). The addictive component of cigarette smoke is nicotine. Our published data shows that nicotine promotes the production of acetylcholine (ACh) in human bronchioalveolar carcinoma cells (BACs) (Lau et al., 2013). ACh functions as a growth factor in human BACs. The following protocol is based on a published protocol by (Song et al., 2003), with some modifications (Lau et al., 2013; Song et al., 2008; Song et al., 2003; Sekhon et al., 2003). An important point to remember is that fetal bovine serum (FBS) contains a high amount of acetylcholine (ACh). Therefore, cells must be cultured in serum-free medium to measure ACh in the culture supernatant. Two aliquots of the culture supernatant are used for analysis. This protocol measures the total choline in the cell supernatent under two conditions: 1) After treatment with acetylcholinesterase (AChE), which converts the ACh to choline (also called the total choline sample) and 2) after measuring the amount of free choline in the sample. The concentration of ACh in the sample calculated by subtracting the free choline from the total choline. PMID- 27390759 TI - Isolation and In vivo Transfer of Antigen Presenting Cells. AB - Transfer of antigen presenting cells in vivo is a method used by immunologists to examine the potency of antigen presentation by a selected population of cells. This method is most commonly used to analyze presentation of protein antigens to MHC class I or II restricted T cells, but it can also be used for studies of nonconventional antigens such as CD1-presented lipids. In a recent study focusing on CD1d-restricted glycolipid antigen presentation to Natural Killer T cells, we compared antigen presenting properties of splenic B cells, CD8alphaPos dendritc cells (DCs) and CD8alphaNeg DCs (Arora et al., 2014). This protocol describes the detailed method used for isolation of these cell populations, and their transfer into recipient mice to analyze their antigen presenting properties. PMID- 27390760 TI - X-gal Staining on Adult Mouse Brain Sections. AB - Knowing expression patterns of given proteins is very important to understand their functions. Immunostaining analysis with specific antibodies is commonly used to identify cells or tissues expressing proteins of interest. Although this technique is regularly used, it requires high quality of specific antibodies and there is no good quality of antibody available for certain proteins. Alternatively, X-gal staining is also used to analyze protein expression pattern. It is simple and routinely used to detect expression pattern of any proteins of interest in vivo. In this method, genetically modified animals that express beta galactosidase under the control of certain regulatory elements will be used to reveal the expression pattern of proteins that use the same regulatory elements. PMID- 27390761 TI - Virus Infection and Titration of SARS-CoV in Mouse Lung. AB - Two critical steps when investigating an animal model of a virus infection are consistently successfully infecting animals and accurately determining viral titers in tissue throughout the course of infection. Here we discuss in detail how to infect mice with SARS-CoV and then quantify the titer of virus in the lung. PMID- 27390762 TI - Measurement of CD8 and CD4 T Cell Responses in Mouse Lungs. AB - Study of the adaptive immune response to a viral challenge in an animal model often includes analysis of the T cell response. Here we discuss in detail the methods that are used to characterize the CD8 and CD4 T cell response following viral challenge in the lung. PMID- 27390763 TI - Helicase Assays. AB - Helicases are a class of enzymes which are motor proteins using energy derived from ATP hydrolysis to move directionally along a nucliec acid phosphodiester backbone (such as DNA, RNA and DNA-RNA hybrids) and separate two annealed nucleic acid strands. Many cellular processes, such as transcription, DNA replication, recombination and DNA repair involve helicase activity. Here, we provide a protocol to analyze helicase activities in vitro. In this protocol, the DNA helicase protein Merkel cell polyomavirus large T-antigen was expressed in the mammalian cell line HEK293 and immoblized on an IgG resin. The helicase assay is performing while the protein is immoblized on IgG resin. PMID- 27390764 TI - Enzymatic Activity Assays for Base Excision Repair Enzymes in Cell Extracts from Vertebrate Cells. AB - We previously reported enzymatic activity assays for the base excision repair (BER) enzymes DNA polymerase beta (pol beta), aprataxin (APTX), and flap endonuclease 1 (FEN1) in cell extracts from Saccharomyces cerevisiae (Caglayan and Wilson, 2014). Here, we describe a method to prepare cell extracts from vertebrate cells to investigate these enzymatic activities for the processing of the 5'-adenylated-sugar phosphate-containing BER intermediate. This new protocol complements our previous publication. The cell lines used are wild-type and APTX deficient human lymphoblast cells from an Ataxia with Oculomotor Apraxia Type 1 (AOA1) disease patient, wild-type and APTX-null DT40 chicken B cells, and mouse embryonic fibroblast (MEF) cells. This protocol is a quick and efficient way to make vertebrate cell extracts without using commercial kits. PMID- 27390765 TI - Non-invasive Intratracheal Instillation in Mice. AB - The intratracheal instillation technique is used to deliver a variety of agents to the lungs ranging from pathogens (bacteria, viruses), toxins, to therapeutic agents. To model lung inflammation and injury, LPS can be administrated via intranasal, intratracheal, or aerosol approaches. Each technique has its limitations. The intratracheal technique can involve the non-invasive instillation method (via the oro-tracheal route) or a direct injection into the trachea. Here, we describe an optimized method for direct visual instillation of LPS via the non-invasive oro-tracheal route. PMID- 27390766 TI - Pyridine Hemochromagen Assay for Determining the Concentration of Heme in Purified Protein Solutions. AB - Heme is a common cofactor in proteins, found in hemoglobin, myoglobin, cytochrome P450, DGCR8, and nitric oxide synthase, among others. This protocol describes a method for quantifying heme that works best in purified protein samples. This protocol might be used to, for example, determine whether a given heme-binding protein is fully occupied by heme, thus allowing correlation of heme content with activity. This requires the absolute heme concentration and an accurate protein concentration. Another use is to determine the extinction coefficients of a heme bound protein. This assay is fast, easy, and reproducible if done correctly. PMID- 27390767 TI - Phenotyping of Live Human PBMC using CyTOFTM Mass Cytometry. AB - Single-cell analysis has become an method of importance in immunology. Fluorescence flow cytometry has been a major player. However, due to issues such as autofluorescence and emission spillover between different fluorophores, alternative techniques are being developed. In recent years, mass cytometry has emerged, wherein antibodies labeled with metal ions are detected by ICP-MS. In order for a cell to be seen, a metal in the mass window must be present; there is no analogous parameter to forward or side scatter. The current mass window selected is approximately AW 103-196, which includes the lanthanides used for most antibody labeling, as well as iridium and rhodium for DNA intercalators. In this protocol, we use a cocktail of antibodies labeled with MAXPAR metal chelating polymers to surface-stain live PBMC that have been previously cryopreserved. Many of these markers were taken from a standard fluorescence phenotyping panel (Maecker et al., 2012). No intracellular antibodies are used. We use a CyTOFTM (Cytometry by Time-Of-Flight) mass cytometer to acquire the ICP MS data. Subsequent analysis of the dual count signal data using FlowJo software allows for cell types to be analyzed based on the dual count signal in each mass channel. The percentage of each cell type is determined and reported as a percent of the parent cell type. PMID- 27390768 TI - Learning by Computer Simulation Does Not Lead to Better Test Performance on Advanced Cardiac Life Support Than Textbook Study. AB - BACKGROUND: For an effective acquisition and the practical application of rapidly increasing amounts of information, computer-based learning has already been introduced in medical education. However, there have been few studies that compare this innovative method to traditional learning methods in studying advanced cardiac life support (ACLS). METHODS: Senior medical students were randomized to computer simulation and a textbook study. Each group studied ACLS for 150 minutes. Tests were done one week before, immediately after, and one week after the study period. Testing consisted of 20 questions. All questions were formulated in such a way that there was a single best answer. Each student also completed a questionnaire designed to assess computer skills as well as satisfaction with and benefit from the study materials. RESULTS: Test scores improved after both textbook study and computer simulation study in both groups but the improvement in scores was significantly higher for the textbook group only immediately after the study. There was no significant difference between groups in their computer skill and satisfaction with the study materials. The textbook group reported greater benefit from study materials than did the computer simulation group. CONCLUSIONS: Studying ACLS with a hard copy textbook may be more effective than computer simulation for the acquisition of simple information during a brief period. However, the difference in effectiveness is likely transient. PMID- 27390769 TI - Implementation of a Research Participant Satisfaction Survey at an Academic Medical Center. AB - This descriptive case study covers the development of a survey to assess research subject satisfaction among those participating in clinical research studies at an academic medical center (AMC). The purpose was twofold: to gauge the effectiveness of the survey, as well as to determine the level of satisfaction of the research participants. The authors developed and implemented an electronic research participant satisfaction survey. It was created to provide research teams at the authors' AMC with a common instrument to capture research participant experiences in order to improve upon the quality of research operations. The instrument captured participant responses in a standardized format. Ultimately, the results are to serve as a means to improve the research experience of participants for single studies, studies conducted within a division or department of the AMC, or across the entire research enterprise at the institution. For ease of use, the survey was created within an electronic data capture system known as REDCap, which is used by a consortium of more than 1,800 institutional partners as a tool from the Clinical and Translational Science Awards (CTSA) program of the National Institutes of Health (NIH). Participants in the survey described in this article were more than 18 years of age and participating in an institutional review board (IRB)-approved study. Results showed that the vast majority of participants surveyed had a positive experience engaging in research at the authors' AMC. Further, the tool was found to be effective in making that determination. The authors hope to expand the use of the survey as a means to increase research satisfaction and quality at their university. PMID- 27390770 TI - A Pilot Psychometric Study on the Validation of the Older Women's Non-Medical Stress Scale (OWN-MSS) on an Ethnically Diverse Sample. AB - INTRODUCTION: Older women often experience various types of stressors, including the death of a spouse and associated financial stress (often with a lack of social support), emotional stress due to factors such as caregiving and being single, and the challenges of the aging process. These circumstances could produce or aggravate anxious symptomatology that can in turn compound the negative effects of aging. A brief scale of perceived stress that is not confounded with health status and covers multiple culturally relevant potential stressors is needed for quick use in busy medical settings. AIM: To assess the reliability and the validity of an original stress scale designed to measure perceptions of stress beyond health status in a non-clinical convenience sample of community-dwelling older women. METHOD: In this cross-sectional pilot investigation, via conducting item-total correlations and correlational tests of validity, we studied the psychometric properties of our measure using data from volunteer older subjects (mainly low-income and from non-Caucasian backgrounds). The domains covered by the nine items of the tool were selected based on a literature review of common stressors experienced by older adults, especially by older women. Data were collected face-to-face using a demographic list, a well established depression measure, a brief posttraumatic stress disorder (PTSD) screener, and our 9-item stress tool. Primary outcomes: reliability and validity of the scale of older women's non-medical stress. Secondary outcomes: demographic characteristics of the sample and correlations between stress items. RESULTS: Based on our sample of older women (N=40, mean age 71 years), good internal consistency between the items of the stress scale was found (Cronbach's a=.66). The findings of the data analyses also revealed that our psychometric tool has good convergent validity with the PTSD screener (r=.53). Moreover, in contrast with most other stress tools, it has strong discriminant validity (r=.11) with a well-validated depression scale. CONCLUSION: Our results suggest that this new measure is psychometrically strong. Future research directions encompass using larger samples, ideally including older men with the modification of the scale's name, as well as validating this tool against more measures. Clinical implications of our findings are briefly discussed. PMID- 27390771 TI - SLC26A11 (KBAT) in Purkinje Cells Is Critical for Inhibitory Transmission and Contributes to Locomotor Coordination. AB - Chloride homeostasis determines the impact of inhibitory synaptic transmission and thereby mediates the excitability of neurons. Even though cerebellar Purkinje cells (PCs) receive a pronounced inhibitory GABAergic input from stellate and basket cells, the role of chloride homeostasis in these neurons is largely unknown. Here we studied at both the cellular and systems physiological level the function of a recently discovered chloride channel, SLC26A11 or kidney brain anion transporter (KBAT), which is prominently expressed in PCs. Using perforated patch clamp recordings of PCs, we found that a lack of KBAT channel in PC specific KBAT KO mice (L7-KBAT KOs) induces a negative shift in the reversal potential of chloride as reflected in the GABAA-receptor-evoked currents, indicating a decrease in intracellular chloride concentration. Surprisingly, both in vitro and in vivo PCs in L7-KBAT KOs showed a significantly increased action potential firing frequency of simple spikes, which correlated with impaired motor performance on the Erasmus Ladder. Our findings support an important role for SLC26A11 in moderating chloride homeostasis and neuronal activity in the cerebellum. PMID- 27390772 TI - Microglial Contact Prevents Excess Depolarization and Rescues Neurons from Excitotoxicity. AB - Microglia survey and directly contact neurons in both healthy and damaged brain, but the mechanisms and functional consequences of these contacts are not yet fully elucidated. Combining two-photon imaging and patch clamping, we have developed an acute experimental model for studying the role of microglia in CNS excitotoxicity induced by neuronal hyperactivity. Our model allows us to simultaneously examine the effects of repetitive supramaximal stimulation on axonal morphology, neuronal membrane potential, and microglial migration, using cortical brain slices from Iba-1 eGFP mice. We demonstrate that microglia exert an acute and highly localized neuroprotective action under conditions of neuronal hyperactivity. Evoking repetitive action potentials in individual layer 2/3 pyramidal neurons elicited swelling of axons, but not dendrites, which was accompanied by a large, sustained depolarization of soma membrane potential. Microglial processes migrated to these swollen axons in a mechanism involving both ATP and glutamate release via volume-activated anion channels. This migration was followed by intensive microglial wrapping of affected axons and, in some cases, the removal of axonal debris that induced a rapid soma membrane repolarization back to resting potentials. When the microglial migration was pharmacologically blocked, the activity-induced depolarization continued until cell death ensued, demonstrating that the microglia-axon contact served to prevent pathological depolarization of the soma and maintain neuronal viability. This is a novel aspect of microglia surveillance: detecting, wrapping, and rescuing neuronal soma from damage due to excessive activity. PMID- 27390773 TI - Cortical Temperature Change: A Tool for Modulating Brain States? PMID- 27390774 TI - Frontostriatal Circuit Dynamics Correlate with Cocaine Cue-Evoked Behavioral Arousal during Early Abstinence. AB - It is thought that frontostriatal circuits play an important role in mediating conditioned behavioral responses to environmental stimuli that were previously encountered during drug administration. However, the neural correlates of conditioned responses to drug-associated cues are not well understood at the level of large populations of simultaneously recorded neurons, or at the level of local field potential (LFP) synchrony in the frontostriatal network. Here we introduce a behavioral assay of conditioned arousal to cocaine cues involving pupillometry in awake head-restrained mice. After just 24 h of drug abstinence, brief exposures to olfactory stimuli previously paired with cocaine injections led to a transient dilation of the pupil, which was greater than the dilation effect to neutral cues. In contrast, there was no cue-selective change in locomotion, as measured by the rotation of a circular treadmill. The behavioral assay was combined with simultaneous recordings from dozens of electrophysiologically identified units in the medial prefrontal cortex (mPFC) and ventral striatum (VS). We found significant relationships between cocaine cue evoked pupil dilation and the proportion of inhibited principal cells in the mPFC and VS. Additionally, LFP coherence analysis revealed a significant correlation between pupillary response and synchrony in the 25-45 Hz frequency band. Together, these results show that pupil dilation is sensitive to drug-associated cues during acute stages of abstinence, and that individual animal differences in this behavioral arousal response can be explained by two complementary measures of frontostriatal network activity. PMID- 27390775 TI - Cell-Type-Selective Effects of Intramembrane Cavitation as a Unifying Theoretical Framework for Ultrasonic Neuromodulation. AB - Diverse translational and research applications could benefit from the noninvasive ability to reversibly modulate (excite or suppress) CNS activity using ultrasound pulses, however, without clarifying the underlying mechanism, advanced design-based ultrasonic neuromodulation remains elusive. Recently, intramembrane cavitation within the bilayer membrane was proposed to underlie both the biomechanics and the biophysics of acoustic bio-effects, potentially explaining cortical stimulation results through a neuronal intramembrane cavitation excitation (NICE) model. Here, NICE theory is shown to provide a detailed predictive explanation for the ability of ultrasonic (US) pulses to also suppress neural circuits through cell-type-selective mechanisms: according to the predicted mechanism T-type calcium channels boost charge accumulation between short US pulses selectively in low threshold spiking interneurons, promoting net cortical network inhibition. The theoretical results fit and clarify a wide array of earlier empirical observations in both the cortex and thalamus regarding the dependence of ultrasonic neuromodulation outcomes (excitation-suppression) on stimulation and network parameters. These results further support a unifying hypothesis for ultrasonic neuromodulation, highlighting the potential of advanced waveform design for obtaining cell-type-selective network control. PMID- 27390776 TI - Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex. AB - Cerebral neocortex development in mammals requires highly orchestrated events involving proliferation, differentiation, and migration of neural progenitors and neurons. Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play crucial roles in migration of postmitotic neurons. We previously reported that conditional knockout of Rapgef2 in dorsal telencephalon (Rapgef2-cKO) resulted in the formation of an ectopic cortical mass (ECM) resembling that of subcortical band heterotopia. Here we show that double knockout of Rapgef6 in Rapgef2-cKO mice (Rapgef2/6-dKO) results in marked enlargement of the ECM. While Rapgef2-cKO affects late-born neurons only, Rapgef2/6-dKO affects both early-born and late born neurons. The Rapgef2-cKO cortex at embryonic day (E) 15.5, and the Rapgef2/6 dKO cortex at E13.5 and E15.5 show disruption of the adherens junctions (AJs) on the apical surface, detachment of radial glial cells (RGCs) from the apical surface and disorganization of the radial glial fiber system, which are accompanied by aberrant distribution of RGCs and intermediate progenitors, normally located in the ventricular zone and the subventricular zone, respectively, over the entire cerebral cortex. Moreover, intrauterine transduction of Cre recombinase into the Rapgef2(flox/flox) brains also results in the apical surface AJ disruption and the RGC detachment from the apical surface, both of which are effectively suppressed by cotransduction of the constitutively active Rap1 mutant Rap1(G12V). These results demonstrate a cell autonomous role of the Rapgef2/6-Rap1 pathway in maintaining the apical surface AJ structures, which is necessary for the proper development of neural progenitor cells. PMID- 27390777 TI - Inhibition of mammillary body neurons by direct activation of Group II metabotropic glutamate receptors. AB - The mammillary body is an important neural component of limbic circuitry implicated in learning and memory. Excitatory and inhibitory inputs, primarily mediated by glutamate and gamma-amino butyric acid (GABA), respectively, converge and integrate in this region, before sending information to the thalamus. One potentially overlooked mechanism for inhibition of mammillary body neurons is through direct activation of Group II metabotropic glutamate receptors (mGluRs). Here, whole-cell patch clamp recordings of in vitro slice preparations containing the mammillary body nuclei of the mouse were employed to record responses to bath application of pharmacological agents to isolate the direct effect of activating Group II mGluRs. Application of the Group II mGluR specific agonist, APDC, resulted in a hyperpolarization of the membrane potential in mammillary body neurons, likely resulting from the opening of a potassium conductance. These data suggest that glutamatergic inputs to the mammillary body may be attenuated via Group II mGluRs and implicates a functional role for these receptors in memory related circuits and broadly throughout the central nervous system. PMID- 27390778 TI - Repurposing tromethamine as inhaled therapy to treat CF airway disease. AB - In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3- and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3- increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3--independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID- 27390779 TI - Potential Roles of Fungal Extracellular Vesicles during Infection. AB - Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Additionally, recent studies have demonstrated that fungal EVs stimulate the host immune system. In this review, putative roles of fungal EVs are discussed, including their potential as vaccination tools and their possible contribution to pathogenesis in invasive fungal diseases. PMID- 27390782 TI - The Microbiome, Antibiotics, and Health of the Pediatric Population. PMID- 27390780 TI - Separate F-Type Plasmids Have Shaped the Evolution of the H30 Subclone of Escherichia coli Sequence Type 131. AB - The extraintestinal pathogenic Escherichia coli (ExPEC) H30 subclone of sequence type 131 (ST131-H30) has emerged abruptly as a dominant lineage of ExPEC responsible for human disease. The ST131-H30 lineage has been well described phylogenetically, yet its plasmid complement is not fully understood. Here, single-molecule, real-time sequencing was used to generate the complete plasmid sequences of ST131-H30 isolates and those belonging to other ST131 clades. Comparative analyses revealed separate F-type plasmids that have shaped the evolution of the main fluoroquinolone-resistant ST131-H30 clades. Specifically, an F1:A2:B20 plasmid is strongly associated with the H30R/C1 clade, whereas an F2:A1:B- plasmid is associated with the H30Rx/C2 clade. A series of plasmid gene losses, gains, and rearrangements involving IS26 likely led to the current plasmid complements within each ST131-H30 sublineage, which contain several overlapping gene clusters with putative functions in virulence and fitness, suggesting plasmid-mediated convergent evolution. Evidence suggests that the H30Rx/C2-associated F2:A1:B- plasmid type was present in strains ancestral to the acquisition of fluoroquinolone resistance and prior to the introduction of a multidrug resistance-encoding gene cassette harboring bla CTX-M-15. In vitro experiments indicated a host strain-independent low frequency of plasmid transfer, differential levels of plasmid stability even between closely related ST131-H30 strains, and possible epistasis for carriage of these plasmids within the H30R/Rx lineages. IMPORTANCE A clonal lineage of Escherichia coli known as ST131 has emerged as a dominating strain type causing extraintestinal infections in humans. The evolutionary history of ST131 E. coli is now well understood. However, the role of plasmids in ST131's evolutionary history is poorly defined. This study utilized real-time, single-molecule sequencing to compare plasmids from various current and historical lineages of ST131. From this work, it was determined that a series of plasmid gains, losses, and recombinational events has led to the currently circulating plasmids of ST131 strains. These plasmids appear to have evolved to acquire similar gene clusters on multiple occasions, suggesting possible plasmid-mediated convergent evolution leading to evolutionary success. These plasmids also appear to be better suited to exist in specific strains of ST131 due to coadaptive mutations. Overall, a series of events has enabled the evolution of ST131 plasmids, possibly contributing to the lineage's success. PMID- 27390781 TI - Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein. AB - Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells. PMID- 27390784 TI - Hepatic expression of miR-122 and antioxidant genes in patients with chronic hepatitis B. AB - INTRODUCTION: The pathogenesis of chronic hepatitis B depends on both, the immune response and oxidative stress. AIM OF THE STUDY: To assess the hepatic expression of miR-122 and the antioxidant genes: HMOX-1, NQO1 and GFER1, in liver biopsy specimens obtained from patients with chronic hepatitis B, with regard to selected clinical and histological parameters, using RT-PCR. RESULTS: The study group comprised 34 HBV-infected patients. Statistically significant associations were found between lower hepatic expression of HMOX-1 and greater severity of liver inflammation (p=0.04). However, significantly higher expression of NQO1 was observed in patients with advanced liver fibrosis (p=0.035). Hepatic expression of miR-122 in HBV patients was not associated with viral load or liver injury. CONCLUSION: The hepatic expression of HMOX-1and NQO1 may be associated with liver injuries in chronic hepatitis B. However, hepatic expression of miR-122 does not seem to correspond to progression of the liver disease. PMID- 27390783 TI - Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses. AB - Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4 ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the prediabetic state. These data provide scientific community valuable metabolic signatures that become the basis for understanding the impact of periodontitis on a systemic disease and potentially targets for therapeutic intervention. PMID- 27390785 TI - Curcumin augments the cytostatic and anti-invasive effects of mitoxantrone on carcinosarcoma cells in vitro. AB - Numerous adverse effects limit the applicability of mitoxantrone for the treatment of drug-resistant tumors, including carcinosarcoma. Here, we estimated the additive effects of mitoxantrone and curcumin, a plant-derived biomolecule isolated from Curcuma longa, on the neoplastic and invasive potential of carcinosarcoma cells in vitro. Curcumin augmented the cytostatic, cytotoxic and anti-invasive effects of mitoxantrone on the Walker-256 cells. It also strengthened the inhibitory effects of mitoxantrone on the motility of drug resistant Walker-256 cells that had retained viability after a long-term mitoxantrone/curcumin treatment. Thus, curcumin reduces the effective doses of mitoxantrone and augments its interference with the invasive potential of drug resistant carcinosarcoma cells. PMID- 27390787 TI - Selective mass spectrometric analysis of thiols using charge-tagged disulfides. AB - A simple chemical derivatization technique was developed for electrospray ionization mass spectrometry (ESI-MS) in which thiols and disulfides may be selectively analyzed in a complex matrix and easily characterized. These reagents enhance detection of thiols and disulfides solely due to the nature of the charge tag derivatization agent and therefore does not require an isotopically labelled substrate. The charged disulfides readily and exclusively react with thiols in a complex matrix in a short amount of time. Furthermore, the synthesis of these reagents is simple and results in a highly pure and stable reagent. The efficacy of this reaction was demonstrated using on-line monitoring, while the scope and usefulness of the reaction was demonstrated in petroleum fractions. PMID- 27390786 TI - The action of ten secreted aspartic proteases of pathogenic yeast Candida albicans on major human salivary antimicrobial peptide, histatin 5. AB - Candida albicans, belonging to the most common fungal pathogens of humans, exploits many virulence factors to infect the host, of which the most important is a family of ten secreted aspartic proteases (Saps) that cleave numerous peptides and proteins, often deregulating the host's biochemical homeostasis. It was recently shown that C. albicans cells can inactivate histatin5 (His5), a salivary histidine-rich anticandidal peptide, through the hydrolytic action of Saps. However, the current data on this subject are incomplete as only four out of ten Saps have been studied with respect to hydrolytic processing of His5 (Sap2, Sap5, Sap9-10). The aim of the study was to investigate the action of all Saps on His5 and to characterize this process in terms of peptide chemistry. It was shown that His5 was degraded by seven out of ten Saps (Sap1-4, Sap7-9) over a broad range of pH. The cleavage rate decreased in an order of Sap2>Sap9>Sap3>Sap7>Sap4>Sap1>Sap8. The degradation profiles for Sap2 and Sap9 were similar to those previously reported; however, in contrast to the previous study, Sap10 was shown to be unable to cleave His5. On a long-time scale, the peptide was completely degraded and lost its antimicrobial potential but after a short period of Sap treatment several shorter peptides (His1-13, His1-17, His1 21) that still decreased fungal survival were released. The results, presented hereby, provide extended characteristics of the action of C. albicans extracellular proteases on His5. Our study contribute to deepening the knowledge on the interactions between fungal pathogens and the human host. PMID- 27390788 TI - Correction: Total viable bacterial count using a real time all-fibre spectroscopic system. AB - Correction for 'Total viable bacterial count using a real time all-fibre spectroscopic system' by E. Bogomolny et al., Analyst, 2013, 138, 4112-4119. PMID- 27390789 TI - A "Virtual Electronic Journal: Interactive, Innovative, Interdisciplinary and International. PMID- 27390790 TI - The Perceived Value of the American Board of Anesthesiology Certificate: A Survey of 2,000 Anesthesiologists. AB - BACKGROUND: The present study was undertaken in order to identify anesthesiologists' perceptions regarding the value of the ABA certificate. METHODS: 2,000 anesthesiologists received a 31-item survey designed to identify their demographics and their assessments of the functional and financial value of the certificate. Functional value was assessed using a five-point scale in the domains of professional recognition, personal satisfaction, job security, mobility and advancement, whether the certificate was necessary to obtain an academic or a clinical position, and whether it served as an indicator of depth or breadth of anesthesia knowledge or of clinical competence. Perceived professional lifetime financial value of the certificate was also assessed. Return response rate was 45.4%. Data were analyzed using descriptive statistics and student's t-tests. RESULTS: The ABA certificate was perceived to be most valuable in obtaining an academic position (3.4 +/- .9) and least valuable in indicating clinical competence (1.6 +/- 1.2). Certified anesthesiologists consistently ascribed greater value to it than non-certified ones (p<.001) on all but the academic domain. No gender differences were observed except that females attributed a greater value to the certificate as a requisite for achieving job security. Sixty percent responded that certified anesthesiologists should earn more than non-certified ones and 54% ascribed to a professional lifetime financial value of over $100,000 to ABA certification. CONCLUSIONS: Although perceived as an objective credentialing instrument which could aid one's career, the ABA certificate was not viewed as an indicator of clinical competence. PMID- 27390791 TI - Continuing Medical Education and The Anesthesiologist. PMID- 27390792 TI - Recruitment of House Staff into Anesthesiology: Factors Responsible for House Staff Selecting Anesthesiology as a Career and Individual Training Program. AB - Due to a variety of factors, there was a recent redistribution of graduating American medical students toward primary care specialties and a decline in the number of applicants seeking training positions in anesthesiology. In the present study, factors responsible for Mayo house staff (i.e., residents and clinical fellows) selecting anesthesiology as a career, and Mayo Clinic as their training program, were identified. We also evaluated their level of satisfaction with their choice of career and training program, and their perceptions of the future for anesthesiology trainees. A cross sectional analysis was conducted using a questionnaire to survey 67 house staff enrolled in the anesthesiology training program at Mayo Clinic, Rochester, MN during the 1995-1996 academic year. All responses were anonymous. Data were analyzed using the chi-square and Mann Whitney rank sum tests. P ? 0.05 was considered statistically significant. Forty eight (72%) of those surveyed responded to the questionnaire. The most frequently cited reasons for selecting anesthesiology as a career included it: is a "hands on" specialty, involves clinical application of physiology and pharmacology, and provides immediate gratification in one's work. The most frequently cited reasons for selecting our training program were the diversity of training experience, prestige associated with Mayo Clinic, and employment opportunities following training. Forty-four (92%) felt downsizing of anesthesiology training programs was a national trend, 26 (54%) anticipated difficulty obtaining a job following training, and 16 (33%) felt they had future job security. Overall, 47 (98%) were happy with their career choice, and 40 (83%) would choose anesthesiology as a career if they were now graduating from medical school. Our data indicate that selection of a career in anesthesiology and training program are strongly associated with concerns regarding educational experiences and postgraduate employment opportunities. More than half anticipated difficulty obtaining postgraduate employment; however, this skepticism was overshadowed by two findings: the trainees reported a very high level of satisfaction in their choice of career and training program, and the vast majority reported they would seek a career in anesthesiology if they were now selecting a medical specialty. Additionally, all 1996 graduates found suitable employment without difficulty. PMID- 27390793 TI - Problem-Based Learning in Anesthesiology: An Evaluative Study of a Medical Student Clerkship. AB - BACKGROUND: Problem-based learning (PBL) in medical education has enjoyed widespread acceptance in recent years, particularly in the basic sciences. However, it has been used less frequently in the clinical education of medical students, and quite infrequently in medical student education on anesthesiology. Critics of PBL emphasize cost factors and a lack of evidence of superior educational outcomes. METHODS: This study reports evaluation data on the use of PBL with fourth year medical students who rotated through a required clerkship in clinical anesthesiology and pharmacology over the course of three academic years. Students were asked to complete evaluation questionnaires concerning the clerkship, with particular attention to PBL and the performance of PBL preceptors. Preceptors were also asked to self-rate their performance by using identical questionnaires. Standardized items across all three years facilitated analysis of student and faculty satisfaction as one outcome of the PBL process. RESULTS: Results indicate that student response to PBL was mixed. Students rated PBL preceptors more favorably than the PBL process itself, and rated resident physician preceptors more favorably than attending physician preceptors. All preceptors rated their own performance lower than did their students. Significant differences between student and faculty opinion of PBL were also noted. Interpretation of results are limited by less than ideal response rates; nevertheless, valuable insight was gained into the perception of PBL in an anesthesiology clerkship. CONCLUSIONS: The success of this educational method may be dependent upon certain factors related to "educational context". Further study is needed of contextual and other factors related to the use of PBL in medical education. PMID- 27390794 TI - EVALUATION, FEEDBACK AND REMEDIATION IN ANESTHESIOLOGY RESIDENCY TRAINING: A SURVEY OF 124 UNITED STATES PROGRAMS. AB - PURPOSE: It was the purpose of this study to provide a review of evaluation, feedback and remediation methods in U.S. residency programs during 1995-96. The information gathered is to serve as a framework for discussions within and amongst programs regarding ways to enhance their current processes of evaluation, feedback and remediation, and to serve a baseline for future assessments. METHODS: A three-page survey was sent to the program director of each of the 145 anesthesiology programs listed in the ACGME/NRMP Directory. Information about the resident evaluation process (including techniques of gathering information, frequency of evaluations, faculty compliance, and modes of offering feedback), departmental clinical competence committee, probation and remediation policies for problem residents, and the use of formal examinations during residency was sought. RESULTS: There was an 86.1% response rate. Frequency of evaluation of residents ranged from daily through quarterly: evaluations used both narrative comments and rating scales in 89% of institutions. Faculty compliance in the evaluation process was greater than 75% in 45.1% of programs. Only 25 programs offered formal training about resident evaluation to their faculty. Clinical competence committee meetings average five times annually and 95% of committees are chaired by someone other than the Department Chairperson. 27% of them have resident members. 67.7% of programs have a written policy regarding problem residents, while 82.2% report having a formal probation policy. 48.3% programs use standardized tests to provide feedback and guidance to their residents. CONCLUSIONS: There is a tremendous variety of techniques and methodologies employed among anesthesiology residency programs with regard to evaluation, feedback, and remediation, within the framework of the ACGME guidelines. Providing faculty training in assessment of, and offering feedback to, residents is one area in which many programs can begin to strengthen their current procedures. PMID- 27390795 TI - ORGANIZATION OF A COMPREHENSIVE ANESTHESIOLOGY ORAL PRACTICE EXAMINATION PROGRAM: Planning, Structure, Startup, Administration, Growth and Evaluation. AB - BACKGROUND: Oral practice examinations (OPEs) are used in many anesthesiology programs to familiarize residents with the format of the oral qualifying examination given by the American Board of Anesthesiology (ABA). The purpose of this communication is to describe the planning, structure, startup, administration, growth and evaluation of a comprehensive oral examination program at a sizeable residency program in the Midwest. METHODS AND RESULTS: A committee of three experienced faculty was formed to plan the effort. Planning involved consideration of format and frequency of administration, timing for best resident and faculty availability, communication, forms design, clerical support, record keeping and quality monitoring. To accommodate resident rotation and faculty work schedules, a semiannual administration schedule on 3-4 consecutive Mondays was chosen. The mock oral format was deliberately constructed to resemble that used by the ABA so as to enhance resident familiarity and comfort with ABA style oral exams. Continued quality improvement tools put in place consisted of regular examiner and examinee inservice sessions, communication and feedback from ABA associate examiners to faculty examiners as well as review of examinee exit questionnaires. A set of OPE databases were constructed so as to facilitate quality monitoring and educational research efforts. Continued administration of the OPE program required ongoing construction of a pool of guided case-oriented questions, selection of appropriate questions based on examinee training exposure, advance publication of the exam calendar and scheduling of recurring examiner and examinee activities. Significant issues which required action by the governing committee were exam timing, avoidance of conflict with clinical demands, use of OPE results, and procurement of training resources. Despite initial skepticism, the OPE program was begun successfully and grew substantially from 56 exams in the first year to 120 exams by year three. The OPE was perceived positively by the majority of residents. 90.2% of exit questionnaires acknowledged specific learning about oral exam technique, while only 0.3% indicated lack of meaningful information exchange at OPE sessions. Fewer than 10% of responses indicated misleading questions or badgering by examiners. Although anxiety remained constant over time, resident preparedness increased with repeat OPE exposure. SUMMARY: A comprehensive mock oral examination of substantial scope was successfully planned, initiated, and developed at our anesthesiology resident training program. It is well accepted by residents and faculty. Its inception was associated with an increase in resident preparedness. Now in its tenth year of existence it continues to be an asset and essential component of our training program. PMID- 27390796 TI - Successful Interactive Large Group Teaching. PMID- 27390797 TI - Improving the Anesthesiology Clerkship for Medical Students. AB - With the current emphasizing primary care specialty, the number of the applicants for anesthesiology residency has declined. In consequence, the medical students' interest in taking the elective anesthesia clerkship was decreased. Through the program redesign, we have improved our anesthesiology clerkship. In order to attract the best and brightest medical students to choose anesthesiology as a career, continuing efforts to improve both quantity and quality of medical students' education in anesthesiology are crucial. PMID- 27390798 TI - Anesthesiology Resident Evaluation Practices: Beginning at Square One. PMID- 27390799 TI - Creation of a Perioperative Medicine Curriculum for an Anesthesiology Residency Program. AB - Because of the increasing expansion of the practice of anesthesiology beyond the borders of the operating room, there is attention being paid to Perioperative Medicine (PM) within anesthesiology training programs. With the elements of PM incorporated into the newest requirements for anesthesiology residency programs by the Residency Review Committee (RRC) for Anesthesiology of the American College of Graduate Medical Education (ACGME), programs are obliged to develop PM curriculum. At the Cleveland Clinic, a PM curriculum was created from existing, diverse elements of the clinical practice. Clinical supervision of the Pre Anesthesia testing center, the Same-Day-Surgery unit, In-House Consultation and the Post-Anesthesia Care Unit were combined into a single teaching service. A didactic curriculum was created, resident function within these units was defined, and weekly teaching sessions were created. The result has been increased clinical teaching of PM, satisfaction of RRC requirements, and improved opportunity for resident learning in these areas. Residents have rated PM within the top 10% of rotations for the first two years of existence. We conclude that a combined service is an excellent approach to the creation of a PM curriculum. PMID- 27390800 TI - In Reply. PMID- 27390801 TI - Author Response. PMID- 27390802 TI - Author Response. PMID- 27390803 TI - [Advanced stage fibrosarcoma of the spermatic cord]. PMID- 27390804 TI - [Bladder urothelial fracture in interstitial cystitis hydrodistention(IC) and painful bladder syndrome (PBS)]. PMID- 27390805 TI - The Editor's offering. PMID- 27390806 TI - Pre-emptive treatment with hyperbaric oxygen following radiation therapy for head and neck cancer may prevent the onset of late radiation tissue injury. PMID- 27390807 TI - Reply. An updated meta-analysis of the relationship between tumour location and preoperative seizure incidence in patients with gliomas. PMID- 27390808 TI - Arriving at the End of a Newly Forged Path: Lessons from the Safety and Adverse Events Committee of the At Home/Chez Soi Project. PMID- 27390809 TI - Caregivers of Orthopedic Trauma Patients: Perspectives on Participating in Caregiver-Related Research. PMID- 27390810 TI - Conceptions of Risk Regarding a Chronic Illness Survey: Perspectives of Participants, Researchers, and Ethics Review Board Members. PMID- 27390811 TI - A Federated Model of IRB Review for Multisite Studies: A Report on the National Children's Study Federated IRB Initiative. PMID- 27390812 TI - No Girls Allowed: A Sponsor's Rejection of One IRB's Contraception Policy. PMID- 27390813 TI - 5 steps to avoid the 2017 meaningful use penalty. PMID- 27390814 TI - Government issues refresher on HIPAA in effort to increase interoperability. PMID- 27390815 TI - EHRs: Practices spend more on IT and enjoy it less. PMID- 27390816 TI - The more things change, the more they stay the same. PMID- 27390838 TI - Characterization of a novel zebrafish (Danio rerio) gene, wdr81, associated with cerebellar ataxia, mental retardation and dysequilibrium syndrome (CAMRQ). AB - BACKGROUND: WDR81 (WD repeat-containing protein 81) is associated with cerebellar ataxia, mental retardation and disequilibrium syndrome (CAMRQ2, [MIM 610185]). Human and mouse studies suggest that it might be a gene of importance during neurodevelopment. This study aimed at fully characterizing the structure of the wdr81 transcript, detecting the possible transcript variants and revealing its expression profile in zebrafish, a powerful model organism for studying development and disease. RESULTS: As expected in human and mouse orthologous proteins, zebrafish wdr81 is predicted to possess a BEACH (Beige and Chediak Higashi) domain, a major facilitator superfamily domain and WD40-repeats, which indicates a conserved function in these species. We observed that zebrafish wdr81 encodes one open reading frame while the transcript has one 5' untranslated region (UTR) and the prediction of the 3' UTR was mainly confirmed along with a detected insertion site in the embryo and adult brain. This insertion site was also found in testis, heart, liver, eye, tail and muscle, however, there was no amplicon in kidney, intestine and gills, which might be the result of possible alternative polyadenylation processes among tissues. The 5 and 18 hpf were critical timepoints of development regarding wdr81 expression. Furthermore, the signal of the RNA probe was stronger in the eye and brain at 18 and 48 hpf, then decreased at 72 hpf. Finally, expression of wdr81 was detected in the adult brain and eye tissues, including but not restricted to photoreceptors of the retina, presumptive Purkinje cells and some neurogenic brains regions. CONCLUSIONS: Taken together these data emphasize the importance of this gene during neurodevelopment and a possible role for neuronal proliferation. Our data provide a basis for further studies to fully understand the function of wdr81. PMID- 27390837 TI - beta-Thalassemia and ocular implications: a systematic review. AB - BACKGROUND: Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major require regular lifelong Red Blood Cell transfusions to survive. Ocular involvement is quite common and may have serious implications. METHODS: Extensive review of observational studies on beta-thalassemia, to determine the prevalence and spectrum of ocular abnormalities, by clinical examination and multimodal imaging, and to investigate risk factors for their development. RESULTS: Frequency of ocular involvement differs among various studies (41.3-85 %, three studies). Ocular findings in beta-thalassemia may correlate to the disease itself, iron overload or the chelating agents used. Beta thalassemia ocular manifestations include ocular surface disease, as demonstrated by tear function parameters (two studies). Lens opacities are present in 9.3-44 % (five studies). Lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively (two studies). Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE), including peau d'orange, angioid streaks, pattern dystrophy-like changes, and optic disc drusen are a consistent finding in seven studies. Patients with PXE-like fundus changes were older than patients without these fundus changes (two studies). Age (two studies) and splenectomy (one study) had the strongest association with presence of PXE-like fundus changes. Increased retinal vascular tortuosity independently of the PXE-like fundus changes was found in 11-17.9 % (three studies), which was associated with aspartate amino transferase, hemoglobin and ferritin levels (two studies). Fundus autofluorescence and electrophysiological testing (ERG and EOG) may indicate initial stages or more widespread injury than is suggested by fundus examination (two studies). CONCLUSIONS: Beta-thalassemia may present with various signs, both structural and functional. Pseudoxanthoma elasticum like fundus changes are a frequent finding in patients with b thalassemia. These changes increase with duration or severity of the disease. Retinal vascular tortuosity may be an additional disease manifestation related to the severity and duration of anemia and independent of the PXE-like syndrome. Patients with long-standing disease need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization. PMID- 27390839 TI - Structural Metastability and Quantum Confinement in Zn1-xCoxO Nanoparticles. AB - This paper investigates the electronic structure of wurtzite (W) and rock-salt (RS) Zn1-xCoxO nanoparticles (NPs) by means of optical measurements under pressure (up to 25 GPa), X-ray absorption, and transmission electron microscopy. W-NPs were chemically synthesized at ambient conditions and RS-NPs were obtained by pressure-induced transformation of W-NPs. In contrast to the abrupt phase transition in W-Zn1-xCoxO as thin film or single crystal, occurring sharply at about 9 GPa, spectroscopic signatures of tetrahedral Co(2+) are observed in NPs from ambient pressure to about 17 GPa. Above this pressure, several changes in the absorption spectrum reveal a gradual and irreversible W-to-RS phase transition: (i) the fundamental band-to-band edge shifts to higher photon energies; (ii) the charge-transfer absorption band virtually disappears (or overlaps the fundamental edge); and (iii) the intensity of the crystal-field absorption peaks of Co(2+) around 2 eV decreases by an order of magnitude and shifts to 2.5 eV. After incomplete phase transition pressure cycles, the absorption edge of nontransformed W-NPs at ambient pressure exhibits a blue shift of 0.22 eV. This extra shift is interpreted in terms of quantum confinement effects. The observed gradual phase transition and metastability are related to the NP size distribution: the larger the NP, the lower the W-to-RS transition pressure. PMID- 27390840 TI - Knowledge and use of unauthorized HIV self-test kits among men who have sex with men in Spain, following approval of an over-the-counter self-test in the U.S: a cross-sectional study. AB - BACKGROUND: Shortly after the approval of an over-the-counter HIV self-test in the US, we conducted a study to estimate the proportion of men who have sex with men (MSM) in Spain who knew that unauthorized HIV self-tests could be purchased online, and the proportion that had already used these tests, as well as their socio-demographic and behavioural correlates. METHODS: Between September 2012 and February 2013, MSM users of gay dating websites were invited to complete an online questionnaire. We calculated estimates of the knowledge and use of unauthorized HIV self-testing and assessed the associated factors by rare event logit regression models. RESULTS: Among 8620 participants, 4.2 % (95 % CI:3.8 4.6) knew they could buy an unauthorized HIV self-test kit online, and 12.7 % (95 % CI:12.0-13.4) thought that such a test might exist, although they had never seen one. Only 0.7 % (95 % CI:0.5-0.9) had ever self-tested. In the multivariable analysis, knowledge of online availability of self-tests was associated with being a non-Latin American foreigner, having at least two previous HIV tests, intending to test for HIV in the next year, and knowing about U.S. approval of self-testing. Ever-use of HIV self-testing was associated with being over 34 years of age, living outside Spain during the last 12 months, and knowing about U.S. approval of self-testing. CONCLUSIONS: Both knowledge and use of unauthorized HIV self-testing among MSM in Spain was very low among HIV negative or untested MSM in Spain. The recent approval in the United Kingdom and France might increase the number of MSM seeking such testing and possibly using unauthorized test kits not meeting quality standards. PMID- 27390841 TI - Fetal hemoglobin level and nutritional status in patients with sickle cell disease. AB - Hydroxyurea is the only medication approved by the U.S. Food and Drug Administration for sickle cell disease, and there is strong evidence to support the efficacy and the cost effectiveness of using hydroxyurea is patients with sickle cell disease by increasing fetal hemoglobin levels. It is important to clarify the relationship between patients' nutritional status/intake and fetal hemoglobin levels. In particular, hydroxyurea has been recommended for patients with poor growth, and the recent guidelines from the National Institute of Health suggested offering hydroxyurea to patients as young as nine month old of age. PMID- 27390842 TI - Epidemiological risk factors for adult dengue in Singapore: an 8-year nested test negative case control study. AB - BACKGROUND: Understanding changes in the ecology and epidemiology of dengue is important to ensure resource intensive control programmes are targeted effectively as well as to inform future dengue vaccination strategies. METHODS: We analyzed data from a multicentre longitudinal prospective study of fever in adults using a nested test negative case control approach to identify epidemiological risk factors for dengue disease in Singapore. From April 2005 to February 2013, adult patients presenting with fever within 72 h at selected public primary healthcare clinics and a tertiary hospital in Singapore were recruited. Acute and convalescent blood samples were collected and used to diagnose dengue using both PCR and serology methods. A dengue case was defined as having a positive RT-PCR result for DENV OR evidence of serological conversion between acute and convalescent blood samples. Similarly, controls were chosen from patients in the cohort who tested negative for dengue using the same laboratory methods. RESULTS: The host epidemiological factors which increased the likelihood of dengue disease amongst adults in Singapore were those aged between 21 and 40 years old (2 fold increase) while in contrast, Malay ethnicity was protective (OR 0.57, 95%CI 0.35 to 0.91) against dengue disease. Spatial factors which increased the odds of acquiring dengue was residing at a foreign workers dormitory or hostel (OR 3.25, 95 % CI 1.84 to 5.73) while individuals living in the North-West region of the country were less likely to get dengue (OR 0.50, 95%CI 0.29 to 0.86). Other factors such as gender, whether one primarily works indoors or outdoors, general dwelling type or floor, the type of transportation one uses to work, travel history, as well as self-reported history of mosquito bite or household dengue/fever were not useful in helping to inform a diagnosis of dengue. CONCLUSIONS: We have demonstrated a test negative study design to better understand the epidemiological risk factors of adult dengue over multiple seasons. We were able to discount other previously speculated factors such as gender, whether one primarily works indoors or outdoors, dwelling floor in a building and the use of public transportation as having no effect on one's risk of getting dengue. PMID- 27390843 TI - Quality specifications in postgraduate medical e-learning: an integrative literature review leading to a postgraduate medical e-learning model. AB - BACKGROUND: E-learning is driving major shifts in medical education. Prioritizing learning theories and quality models improves the success of e-learning programs. Although many e-learning quality standards are available, few are focused on postgraduate medical education. METHODS: We conducted an integrative review of the current postgraduate medical e-learning literature to identify quality specifications. The literature was thematically organized into a working model. RESULTS: Unique quality specifications (n = 72) were consolidated and re organized into a six-domain model that we called the Postgraduate Medical E learning Model (Postgraduate ME Model). This model was partially based on the ISO 19796 standard, and drew on cognitive load multimedia principles. The domains of the model are preparation, software design and system specifications, communication, content, assessment, and maintenance. CONCLUSION: This review clarified the current state of postgraduate medical e-learning standards and specifications. It also synthesized these specifications into a single working model. To validate our findings, the next-steps include testing the Postgraduate ME Model in controlled e-learning settings. PMID- 27390844 TI - Family experiences of infant and young child feeding in lower-income countries: protocol for a systematic review of qualitative studies. AB - BACKGROUND: Infant and young child feeding practices, including breastfeeding and complementary feeding of children under 2 years old, are crucially influenced by parent and family perceptions and experiences. Given the urgent need to improve nutrition of young children in low- and low-middle-income countries, both for reduction of morbidity and mortality in childhood and for future health outcomes, we propose to systematically review and synthesize available qualitative data specifically related to infant and young child feeding practices of parents and families in these settings, which may provide greater insights into barriers and facilitators to recommended feeding practices. METHODS/DESIGN: The proposed study will systematically review existing qualitative research reporting infant and young child feeding practices from low- and low-middle-income settings. The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement will be used for reporting the stages of the review and dissemination. The search period will include all studies published from 2006 to 2016. The study selection process will follow established and recommended guidelines for reviews, and quality assessment will be conducted in two phases using critical appraisal and subsequently a confidence in findings approach derived from Grading of Recommendations, Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative (GRADE-CERQual). A full synthesis of the studies identified by the review will begin with thematic analysis and be followed by an interpretive approach to provide actionable information on the topic. DISCUSSION: The findings will provide insight into the barriers and facilitators related to behavior that may hinder or enable implementation of interventions aimed at improving infant and young child feeding practices in lower-income settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035677. PMID- 27390845 TI - Prognostic impact of circulating tumor cell apoptosis and clusters in serial blood samples from patients with metastatic breast cancer in a prospective observational cohort. AB - BACKGROUND: Presence of circulating tumor cells (CTCs) is a validated prognostic marker in metastatic breast cancer. Additional prognostic information may be obtained by morphologic characterization of CTCs. We explored whether apoptotic CTCs, CTC clusters and leukocytes attached to CTCs are associated with breast cancer subtype and prognosis at base-line (BL) and in follow-up (FU) blood samples in patients with metastatic breast cancer scheduled for first-line systemic treatment. METHODS: Patients with a first metastatic breast cancer event were enrolled in a prospective observational study prior to therapy initiation and the CellSearch system (Janssen Diagnostics) was used for CTC enumeration and characterization. We enrolled patients (N = 52) with >=5 CTC/7.5 ml blood at BL (median 45, range 5-668) and followed them with blood sampling for 6 months during therapy. CTCs were evaluated for apoptotic changes, CTC clusters (>=3 nuclei), and leukocytes associated with CTC (WBC-CTC, >=1 CTC + >=1 leukocytes) at all time-points by visual examination of the galleries generated by the CellTracks Analyzer. RESULTS: At BL, patients with triple-negative and HER2 positive breast cancer had blood CTC clusters present more frequently than patients with hormone receptor-positive cancer (P = 0.010). No morphologic characteristics were associated with prognosis at BL, whereas patients with apoptotic CTCs or clusters in FU samples had worse prognosis compared to patients without these characteristics with respect to progression-free (PFS) and overall survival (OS) (log-rank test: P = 0.0012 or lower). Patients with apoptotic or clustered CTCs at any time-point had impaired prognosis in multivariable analyses adjusting for number of CTCs and other prognostic factors (apoptosis: HROS = 25, P < 0.001; cluster: HROS = 7.0, P = 0.006). The presence of WBC-CTCs was significantly associated with an inferior prognosis in terms of OS at 6 months in multivariable analysis. CONCLUSIONS: Patients with a continuous presence of apoptotic or clustered CTCs in FU samples after systemic therapy initiation had worse prognosis than patients without these CTC characteristics. In patients with >=5 CTC/7.5 ml blood at BL, morphologic characterization of persistent CTCs could be an important prognostic marker during treatment, in addition to CTC enumeration alone. Clinical Trials (NCT01322893), registration date 21 March 2011. PMID- 27390846 TI - Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants. AB - OBJECTIVE: To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. METHODS: Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. RESULTS: We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6-13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0-12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. CONCLUSION: The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment. PMID- 27390849 TI - Pulmonary function and health-related quality of life 1-year follow up after cardiac surgery. AB - BACKGROUND: Pulmonary function is severely reduced in the early period after cardiac surgery, and impairments have been described up to 4-6 months after surgery. Evaluation of pulmonary function in a longer perspective is lacking. In this prospective study pulmonary function and health-related quality of life were investigated 1 year after cardiac surgery. METHODS: Pulmonary function measurements, health-related quality of life (SF-36), dyspnoea, subjective breathing and coughing ability and pain were evaluated before and 1 year after surgery in 150 patients undergoing coronary artery bypass grafting, valve surgery or combined surgery. RESULTS: One year after surgery the forced vital capacity and forced expiratory volume in 1 s were significantly decreased (by 4-5 %) compared to preoperative values (p < 0.05). Saturation of peripheral oxygen was unchanged 1 year postoperatively compared to baseline. A significantly improved health-related quality of life was found 1 year after surgery, with improvements in all eight aspects of SF-36 (p < 0.001). Sternotomy-related pain was low 1 year postoperatively at rest (median 0 [min-max; 0-7]), while taking a deep breath (0 [0-4]) and while coughing (0 [0-8]). A more pronounced decrease in pulmonary function was associated with dyspnoea limitations and impaired subjective breathing and coughing ability. CONCLUSIONS: One year after cardiac surgery static and dynamic lung function measurements were slightly decreased, while health-related quality of life was improved in comparison to preoperative values. Measured levels of pain were low and saturation of peripheral oxygen was same as preoperatively. PMID- 27390847 TI - A Phase Ib/II Study Evaluating the Combination of Weekly Docetaxel and Cisplatin Together with Capecitabine and Bevacizumab in Patients with Advanced Esophago Gastric Cancer. AB - INTRODUCTION: Current treatment options for advanced esophagogastric cancer (AEGC) are still unsatisfactory. The aim of this prospective phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. METHODS: Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2 days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX (phase Ib part) and to determine the tumor response rate (phase II part). RESULTS: The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade >=3 adverse events were documented in 18 patients (82%), usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. The recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). Hence, the objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. For the 17 patients treated at the MTD, the objective response rate was 41% and the disease control rate was 88%. The median overall survival (OS) for these patients was 13.9 months (range, 1.5-52.2 months) and the median progression-free survival was 7.6 months (range, 1.3-26.6 months). The 2-year OS rate reached 23.7%. CONCLUSIONS: AVDCX was associated with a high rate of regimen related fatal adverse events and is not appropriate for further development in AEGC patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00845884. PMID- 27390850 TI - Calcium Influx of Mast Cells Is Inhibited by Aptamers Targeting the First Extracellular Domain of Orai1. AB - Using the systematic evolution of ligands by exponential enrichment (SELEX) method, we identified oligonucleotides that bind to the first extracellular domain of the Orai1 protein with high affinities and high specificities. These ligands were isolated from a random single-strand DNA (ssDNA) library with 40 randomized sequence positions, using synthesized peptides with amino acid sequences identical to the first extracellular domain of the Orai1 protein as the targets for SELEX selection. Seven aptamers were obtained after 12 rounds of SELEX. An enzyme-linked oligonucleotide assay (ELONA) was performed to determine the affinities of the aptamers. Aptamer Y1 had the highest affinity (Kd = 1.72*10 8 mol/L) and was selected for functional experiments in mast cells. Using LAD2 cells with the human high-affinity IgE receptor and Ca2+ release activation channel (CRAC), we demonstrated that Aptamer Y1 blocked IgE-mediated beta hexosaminidase release from cells triggered by biotin-IgE and streptavidin. A specific binding assay showed that Aptamer Y1 not only bound the Orai1 peptide specifically but also that the Orai1 peptide did not bind significantly to other random oligonucleotide molecules. Furthermore, Aptamer Y1 regulation of intracellular Ca2+ mobilization was investigated by probing intracellular Ca2+ with a Fluo-4-AM fluorescent probe. We found that Aptamer Y1 inhibits Ca2+ influx into antigen-activated mast cells. These results indicate that the target of Aptamer Y1 in the degranulation pathway is upstream of Ca2+ influx. Therefore, these oligonucleotide agents represent a novel class of CRAC inhibitors that may be useful in the fight against allergic diseases. PMID- 27390851 TI - Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge. AB - We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and energy balance, and genetic and epigenetic alterations that are selected during cancer evolution. PMID- 27390853 TI - Systematic comparison of the functional physico-chemical characteristics and biocidal activity of microbial derived biosurfactants on blood-derived and breast cancer cells. AB - HYPOTHESIS: The cytotoxicity of biosurfactants on cell membranes may be influenced by composition of their hydrophilic head and hydrophobic tails. It is hypothesised that they form mixed micelles which exert a detergent-like effect that disrupts the plasma membrane. The functional physico-chemical and biocidal characteristics of four biosurfactants were concurrently investigated to determine which of their structural characteristics may be tuned for greater efficacy. EXPERIMENTS: Rhamnolipid-95, rhamnolipid-90, surfactin and sophorolipid were characterised using FTIR, LC-MS, HPLC, surface tension and critical micelle concentration. Their biocidal activity against HEK 293, MCF-7 and THP-1 cell lines were investigated by MTT assay, using doxorubicin as cytotoxic control. Growth curves were established for all cell lines using trypan blue (TB) and MTT assays, corresponding doubling time (DT) and growth rate were obtained and compared. FINDINGS: HEK 293 cell-line had the highest growth rate amongst the three cell lines. For TB assay, growth of HEK 293>THP-1 and for MTT, HEK 293>MCF 7 while the DT was in the order of THP-1>MCF-7>HEK 293. Sophorolipid showed anti proliferative activity comparable to doxorubicin on THP-1>MCF-7>HEK 293. THP-1 showed high sensitivity to sophorolipid with IC50 of 10.50, 25.58 and 6.78(MUg/ml) after 24, 48 and 72h respectively. However, sophorolipid was cytotoxic from 24 to 72h on HEK 293 cell lines with IC50 of 21.53, 40.57 and 27.53MUg/ml respectively. Although, doxorubicin showed higher anti-proliferative activity than all biosurfactants, it had poorer selectivity index for the same time durations compared to the biosurfactants. This indicates that biosurfactants were more effective for slowing the growth of the tested cancer cell lines and hence may be potential candidates for use in human cancer therapy. Physico chemical characteristics of the biosurfactants suggest that their mechanism of action may be due to activity on the cell membrane. PMID- 27390854 TI - The internal structure of poly(methyl methacrylate) latexes in nonpolar solvents. AB - HYPOTHESIS: Poly(methyl methacrylate) (PMMA) latexes in nonpolar solvents are an excellent model system to understand phenomena in low dielectric media, and understanding their internal structure is critical to characterizing their performance in both fundamental studies of colloidal interactions and in potential industrial applications. Both the PMMA cores and the poly(12 hydroxystearic acid) (PHSA) shells of the latexes are known to be penetrable by solvent and small molecules, but the relevance of this for the properties of these particles is unknown. EXPERIMENTS: These particles can be prepared in a broad range of sizes, and two PMMA latexes dispersed in n-dodecane (76 and 685nm in diameter) were studied using techniques appropriate to their size. Small-angle scattering (using both neutrons and X-rays) was used to study the small latexes, and analytical centrifugation was used to study the large latexes. These studies enabled the calculation of the core densities and the amount of solvent in the stabilizer shells for both latexes. Both have consequences on interpreting measurements using these latexes. FINDINGS: The PHSA shells are highly solvated (~85% solvent by volume), as expected for effective steric stabilizers. However, the PHSA chains do contribute to the intensity of neutron scattering measurements on concentrated dispersions and cannot be ignored. The PMMA cores have a slightly lower density than PMMA homopolymer, which shows that only a small free volume is required to allow small molecules to penetrate into the cores. Interestingly, the observations are essentially the same, regardless of the size of the particle; these are general features of these polymer latexes. Despite the latexes being used as a model physical system, the internal chemical structure is complex and must be fully considered when characterizing them. PMID- 27390852 TI - Systems Genetic Analyses Highlight a TGFbeta-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease. AB - Recent systems-based analyses have demonstrated that sleep and stress traits emerge from shared genetic and transcriptional networks, and clinical work has elucidated the emergence of sleep dysfunction and stress susceptibility as early symptoms of Huntington's disease. Understanding the biological bases of these early non-motor symptoms may reveal therapeutic targets that prevent disease onset or slow disease progression, but the molecular mechanisms underlying this complex clinical presentation remain largely unknown. In the present work, we specifically examine the relationship between these psychiatric traits and Huntington's disease (HD) by identifying striatal transcriptional networks shared by HD, stress, and sleep phenotypes. First, we utilize a systems-based approach to examine a large publicly available human transcriptomic dataset for HD (GSE3790 from GEO) in a novel way. We use weighted gene coexpression network analysis and differential connectivity analyses to identify transcriptional networks dysregulated in HD, and we use an unbiased ranking scheme that leverages both gene- and network-level information to identify a novel astrocyte-specific network as most relevant to HD caudate. We validate this result in an independent HD cohort. Next, we computationally predict FOXO3 as a regulator of this network, and use multiple publicly available in vitro and in vivo experimental datasets to validate that this astrocyte HD network is downstream of a signaling pathway important in adult neurogenesis (TGFbeta-FOXO3). We also map this HD-relevant caudate subnetwork to striatal transcriptional networks in a large (n = 100) chronically stressed (B6xA/J)F2 mouse population that has been extensively phenotyped (328 stress- and sleep-related measurements), and we show that this striatal astrocyte network is correlated to sleep and stress traits, many of which are known to be altered in HD cohorts. We identify causal regulators of this network through Bayesian network analysis, and we highlight their relevance to motor, mood, and sleep traits through multiple in silico approaches, including an examination of their protein binding partners. Finally, we show that these causal regulators may be therapeutically viable for HD because their downstream network was partially modulated by deep brain stimulation of the subthalamic nucleus, a medical intervention thought to confer some therapeutic benefit to HD patients. In conclusion, we show that an astrocyte transcriptional network is primarily associated to HD in the caudate and provide evidence for its relationship to molecular mechanisms of neural stem cell homeostasis. Furthermore, we present a unified systems-based framework for identifying gene networks that are associated with complex non-motor traits that manifest in the earliest phases of HD. By analyzing and integrating multiple independent datasets, we identify a point of molecular convergence between sleep, stress, and HD that reflects their phenotypic comorbidity and reveals a molecular pathway involved in HD progression. PMID- 27390855 TI - Ferric ion-assisted in situ synthesis of silver nanoplates on polydopamine-coated silk. AB - In the present study, a ferric ion (Fe(3+))-assisted in situ synthesis approach was developed to grow silver (Ag) nanoplates on the polydopamine (PDA)-coated silk without the use of additional reductants. The essential role of Fe(3+) in the formation of Ag nanoplates is revealed by comparing the morphologies of Ag nanostructures prepared on the silk-coated PDA film with/without Fe(3+) doping. Scanning electron micrographs show that high-density Ag nanoplates could be synthesized in the reaction system containing 50MUg/mL FeCl3 and 50mM AgNO3. The size of the Ag nanoplate could be tuned by adjusting the reaction duration. Based on the data, a mechanism involving the Fe(3+)-selected growth of Ag atoms along the certain crystal faces was proposed to explain the fabrication process. Transmission electron microscopy and X-ray diffractometry indicate that the Ag nanoplates possess good crystalline structures. Raman spectra demonstrate that the nanoplates could strongly enhance the Raman scattering of the PDA molecules. The Ag nanoplate-coated silk could be utilized as a flexible substrate for the development of surface-enhanced Raman scattering biosensors. PMID- 27390856 TI - Fungal Peritonitis: Underestimated Disease in Critically Ill Patients with Liver Cirrhosis and Spontaneous Peritonitis. AB - INTRODUCTION: Spontaneous peritonitis, especially spontaneous fungal peritonitis (SFP), is an important and potentially fatal complication in patients with endstage liver disaese. We evaluated potential risk factors, microbiological findings, and outcome of patients with SFP compared to spontaneous bacterial peritonitis (SBP) in critically ill patients. METHODS: Retrospective analyses of critically ill patients with suspected spontaneous peritonitis. RESULTS: Out of 205 patients, 20 (10%) had SFP, 28 (14%) had SBP, 48 (24%) had peritonitis without microbiological findings (SP) and 109 (52%) had no-peritonitis (NP). APACHE II and SOFA score were significantly higher in patients with SFP (26; 22 28; p<0.004 and 16; 14-18; p<0.002), SBP (26; 22-28; p<0.004 and 16; 14-18; p<0.002) and SP (24; 18-30; p<0.045 and 14; 10-18; p<0.044) as compared to NP (22; 16-24 and 12; 10-14). CHILD Pugh classification was mainly CHILD C and MELD Score was in patients with SFP (34; 18-40; p<0.001), SBP (32;12-40 p<0.002) and SP (29; 14-40 p<0.003) significantly higher as compared to NP (25;8-40). Nosocomial peritonitis could be significantly more often found in patients with SFP (65%; p<0.023) and SBP (62%, p<0.030) as compared to SP (51 p = 0.243) and NP (45%). Antibiotic pretreatment last 3 month prior peritonitis was significantly more often in patients with SFP (85%; p<0.002), SBP (71%, p<0.033), and SP (56; p<0.040) as compared to NP (33%). Candida albicans (60%; 12/20) was the most common isolated fungus, followed by Candida glabrata (13%) and Candida krusei (13%). Mortality rate was significantly higher in patients with SFP (90%, p<0.001), followed by SBP (75%; p<0.001) and SP (69%; p<0.001) as compared to NP (45%). CONCLUSION: SFP is not a rare complication in end stage liver disease which is associated with increased mortality. Physicians should be aware of SFP in patients with CHILD C liver cirrhosis, elevated MELD score, antibiotic pretreatment and nosocomial peritonitis. PMID- 27390857 TI - Blood Glutamate Levels in Autism Spectrum Disorder: A Systematic Review and Meta Analysis. AB - OBJECTIVE: Glutamate plays an important role in brain development, neuronal migration, differentiation, survival and synaptogenesis. Recent studies have explored the relationship between blood glutamate levels and autism spectrum disorder (ASD). However, the findings are inconsistent. We undertook the first systematic review with a meta-analysis of studies examining blood glutamate levels in ASD compared with controls. METHODS: A literature search was conducted using PubMed, Embase, and the Cochrane Library for studies published before March 2016. A random-effects model was used to calculate the pooled standardized mean difference (SMD) of the outcomes. Subgroup analyses were used to explore the potential sources of heterogeneity, and the publication bias was estimated using Egger's tests. RESULTS: Twelve studies involving 880 participants and 446 incident cases were included in this meta-analysis. The meta-analysis provided evidence for higher blood glutamate levels in ASD [SMD = 0.99, 95% confidence interval (95% CI) = 0.58-1.40; P < 0.001] with high heterogeneity (I2 = 86%, P < 0.001) across studies. The subgroup analyses revealed higher glutamate levels in ASD compared with controls in plasma [SMD = 1.04, 95% CI = 0.58-1.50; P < 0.001] but not true in serum [SMD = 0.79, 95% CI = -0.41-1.99; P = 0.20]. Studies employing high performance liquid chromatography (HPLC) or liquid chromatography tandem mass spectrometry (LC-MS) assays also revealed higher blood glutamate levels in ASD. A sensitivity analysis found that the results were stable, and there was no evidence of publication bias. CONCLUSIONS: Blood glutamate levels might be a potential biomarker of ASD. PMID- 27390859 TI - Shoulder Joint and Muscle Characteristics Among Weight-Training Participants With and Without Impingement Syndrome. AB - Kolber, MJ, Hanney, WJ, Cheatham, SW, Salamh, PA, Masaracchio, M, and Liu, X. Shoulder joint and muscle characteristics among weight-training participants with and without impingement syndrome. J Strength Cond Res 31(4): 1024-1032, 2017 Subacromial impingement syndrome (SIS) has been reported as an etiological source of shoulder pain among weight-training (WT) participants; however, a paucity of evidence exists to describe intrinsic risk factors. The purpose of this study was to investigate specific risk-related joint and muscle adaptations among WT participants identified as having SIS based on a previously validated clinical testing cluster. Fifty-five men (mean age 27.3 years) who participated in recreational WT a minimum of 2 d.wk were recruited, including 24 individuals with SIS and 31 without SIS serving as controls. Active range of motion (AROM), bodyweight-adjusted strength values, and strength ratios were compared between groups. Significant differences were present as WT participants with SIS had decreased internal and external rotation AROM (p <= 0.016) and decreased bodyweight-adjusted strength values of the external rotator and lower trapezius musculature (p <= 0.02) when compared with WT participants without SIS. Select strength ratios were greater in the SIS group (p <= 0.004) implying agonist to antagonist muscle imbalances. The impaired joint and muscle characteristics identified among WT participants with SIS are not without consequence, as they are associated with shoulder disorders in both general and athletic populations. Practical applications for these findings may reside in exercise prescription that addresses internal rotation mobility, mitigates training bias, and favors muscles responsible for stabilization, such as the external rotators and lower trapezius. Strength and conditioning professionals should consider risk-related adaptations associated with WT when prescribing upper-extremity exercises. PMID- 27390858 TI - Assessing the Complex and Evolving Relationship between Charges and Payments in US Hospitals: 1996 - 2012. AB - BACKGROUND: In 2013 the United States spent $2.9 trillion on health care, more than in any previous year. Much of the debate around slowing health care spending growth focuses on the complicated pricing system for services. Our investigation contributes to knowledge of health care spending by assessing the relationship between charges and payments in the inpatient hospital setting. In the US, charges and payments differ because of a complex set of incentives that connect health care providers and funders. Our methodology can also be applied to adjust charge data to reflect actual spending. METHODS: We extracted cause of health care encounter (cause), primary payer (payer), charge, and payment information for 50,172 inpatient hospital stays from 1996 through 2012. We used linear regression to assess the relationship between charges and payments, stratified by payer, year, and cause. We applied our estimates to a large, nationally representative hospital charge sample to estimate payments. RESULTS: The average amount paid per $1 charged varies significantly across three dimensions: payer, year, and cause. Among the 10 largest causes of health care spending, average payments range from 23 to 55 cents per dollar charged. Over time, the amount paid per dollar charged is decreasing for those with private or public insurance, signifying that inpatient charges are increasing faster than the amount insurers pay. Conversely, the amount paid by out-of-pocket payers per dollar charged is increasing over time for several causes. Applying our estimates to a nationally representative hospital charge sample generates payment estimates which align with the official US estimates of inpatient spending. CONCLUSIONS: The amount paid per $1 charged fluctuates significantly depending on the cause of a health care encounter and the primary payer. In addition, the amount paid per charge is changing over time. Transparent accounting of hospital spending requires a detailed assessment of the substantial and growing gap between charges and payments. Understanding what is driving this divergence and generating accurate spending estimates can inform efforts to contain health care spending. PMID- 27390860 TI - Prediction of Metabolic Pathway Involvement in Prokaryotic UniProtKB Data by Association Rule Mining. AB - The widening gap between known proteins and their functions has encouraged the development of methods to automatically infer annotations. Automatic functional annotation of proteins is expected to meet the conflicting requirements of maximizing annotation coverage, while minimizing erroneous functional assignments. This trade-off imposes a great challenge in designing intelligent systems to tackle the problem of automatic protein annotation. In this work, we present a system that utilizes rule mining techniques to predict metabolic pathways in prokaryotes. The resulting knowledge represents predictive models that assign pathway involvement to UniProtKB entries. We carried out an evaluation study of our system performance using cross-validation technique. We found that it achieved very promising results in pathway identification with an F1-measure of 0.982 and an AUC of 0.987. Our prediction models were then successfully applied to 6.2 million UniProtKB/TrEMBL reference proteome entries of prokaryotes. As a result, 663,724 entries were covered, where 436,510 of them lacked any previous pathway annotations. PMID- 27390861 TI - Analysis of Genetic Variation across the Encapsidated Genome of Microplitis demolitor Bracovirus in Parasitoid Wasps. AB - Insect parasitoids must complete part of their life cycle within or on another insect, ultimately resulting in the death of the host insect. One group of parasitoid wasps, the 'microgastroid complex' (Hymenoptera: Braconidae), engage in an association with beneficial symbiotic viruses that are essential for successful parasitism of hosts. These viruses, known as Bracoviruses, persist in an integrated form in the wasp genome, and activate to replicate in wasp ovaries during development to ultimately be delivered into host insects during parasitism. The lethal nature of host-parasitoid interactions, combined with the involvement of viruses in mediating these interactions, has led to the hypothesis that Bracoviruses are engaged in an arms race with hosts, resulting in recurrent adaptation in viral (and host) genes. Deep sequencing was employed to characterize sequence variation across the encapsidated Bracovirus genome within laboratory and field populations of the parasitoid wasp species Microplitis demolitor. Contrary to expectations, there was a paucity of evidence for positive directional selection among virulence genes, which generally exhibited signatures of purifying selection. These data suggest that the dynamics of host-parasite interactions may not result in recurrent rounds of adaptation, and that adaptation may be more variable in time than previously expected. PMID- 27390863 TI - Electrostatic model of the energy-bending within organic semiconductors: experiment and simulation. AB - The interfacial properties between electrodes and the various organic layers that comprise an organic electronic device are of direct relevance in understanding charge injection, extraction and generation. The energy levels and energy-bending of three interfaces; indium tin oxide (ITO)/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT: PSS), ITO/poly(N-vinylcarbazole) (PVK) and PEDOT: PSS/PVK were measured using ultraviolet photoelectron spectroscopy (UPS) and x ray photoelectron spectroscopy (XPS). By decoupling the vacuum shift and energy bending, the energy-bending at these interfaces can be simulated using an electrostatic model that takes into account the energetic disorder of the polymers. The model is further extended to include blended mixtures of semiconductors at differing concentrations and it was found that a very good agreement exists between the experiment and theory for all interfaces. This suggests that the electrostatic model can be used to describe energy-bending at the interface between any organic semiconductors. Further investigation into the effect of the Gaussian density of states width on energy-bending is warranted. PMID- 27390862 TI - Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma. AB - BACKGROUND: Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors. METHODS: The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR. RESULTS: Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses. CONCLUSIONS: Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome. PMID- 27390864 TI - Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa. AB - BACKGROUND: In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ MUl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. METHODS: We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. RESULTS: In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). CONCLUSIONS: In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved. PMID- 27390865 TI - The Cost of Relapsing-Remitting Multiple Sclerosis Patients Who Develop Neutralizing Antibodies during Interferon Beta Therapy. AB - BACKGROUND: Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with interferon beta (IFN beta) can develop neutralizing antibodies (NAbs) that reduce treatment efficacy. Several clinical studies explored the association of NAb+ status with increased disease activity. OBJECTIVE: The aim of this study was to estimate the cost of RRMS patients who develop NAbs while treated with IFN beta by the Italian National Healthcare Service (NHS) and the Italian Society perspectives. METHODS: The clinical data derived from a published observational study on 567 RRMS Italian patients treated with IFN beta. The management cost data derived from the published literature. Cost data were inflated to Euro 2014. RESULTS: The annual direct cost to treat a patient was estimated in ?15,428 in the NAb+ cohort and ?14,317 in the NAb- cohort. The annual societal cost was estimated in ?33,890 and ?30,790 in NAb+ and NAb- patients, respectively. The cost increase related to the NAb+ status was ?3,100 in the Italian societal perspective and ?1,111 in the Italian NHS perspective. CONCLUSION: The results of this economic evaluation suggest the presence of an association between NAb+ status and increased costs for the management of RRMS in Italy. Further pharmacoeconomic research will be needed to confirm this first result. PMID- 27390866 TI - Genetic Variants in the STMN1 Transcriptional Regulatory Region Affect Promoter Activity and Fear Behavior in English Springer Spaniels. AB - Stathmin 1 (STMN1) is a neuronal growth-associated protein that is involved in microtubule dynamics and plays an important role in synaptic outgrowth and plasticity. Given that STMN1 affects fear behavior, we hypothesized that genetic variations in the STMN1 transcriptional regulatory region affect gene transcription activity and control fear behavior. In this study, two single nucleotide polymorphisms (SNPs), g. -327 A>G and g. -125 C>T, were identified in 317 English Springer Spaniels. A bioinformatics analysis revealed that both were loci located in the canine STMN1 putative promoter region and affected transcription factor binding. A statistical analysis revealed that the TT genotype at g.-125 C>T produced a significantly greater fear level than that of the CC genotype (P < 0.05). Furthermore, the H4H4 (GTGT) haplotype combination was significantly associated with canine fear behavior (P < 0.01). Using serially truncated constructs of the STMN1 promoters and the luciferase reporter, we found that a 395 bp (-312 nt to +83 nt) fragment constituted the core promoter region. The luciferase assay also revealed that the H4 (GT) haplotype promoter had higher activity than that of other haplotypes. Overall, our results suggest that the two SNPs in the canine STMN1 promoter region could affect canine fear behavior by altering STMN1 transcriptional activity. PMID- 27390867 TI - Do Dynamic Compared to Static Facial Expressions of Happiness and Anger Reveal Enhanced Facial Mimicry? AB - Facial mimicry is the spontaneous response to others' facial expressions by mirroring or matching the interaction partner. Recent evidence suggested that mimicry may not be only an automatic reaction but could be dependent on many factors, including social context, type of task in which the participant is engaged, or stimulus properties (dynamic vs static presentation). In the present study, we investigated the impact of dynamic facial expression and sex differences on facial mimicry and judgment of emotional intensity. Electromyography recordings were recorded from the corrugator supercilii, zygomaticus major, and orbicularis oculi muscles during passive observation of static and dynamic images of happiness and anger. The ratings of the emotional intensity of facial expressions were also analysed. As predicted, dynamic expressions were rated as more intense than static ones. Compared to static images, dynamic displays of happiness also evoked stronger activity in the zygomaticus major and orbicularis oculi, suggesting that subjects experienced positive emotion. No muscles showed mimicry activity in response to angry faces. Moreover, we found that women exhibited greater zygomaticus major muscle activity in response to dynamic happiness stimuli than static stimuli. Our data support the hypothesis that people mimic positive emotions and confirm the importance of dynamic stimuli in some emotional processing. PMID- 27390869 TI - Dynamics of Ecosystem Services during Forest Transitions in Reventazon, Costa Rica. AB - The forest transition framework describes the temporal changes of forest areas with economic development. A first phase of forest contraction is followed by a second phase of expansion once a turning point is reached. This framework does not differentiate forest types or ecosystem services, and describes forests regardless of their contribution to human well-being. For several decades, deforestation in many tropical regions has degraded ecosystem services, such as watershed regulation, while increasing provisioning services from agriculture, for example, food. Forest transitions and expansion have been observed in some countries, but their consequences for ecosystem services are often unclear. We analyzed the implications of forest cover change on ecosystem services in Costa Rica, where a forest transition has been suggested. A review of literature and secondary data on forest and ecosystem services in Costa Rica indicated that forest transition might have led to an ecosystem services transition. We modeled and mapped the changes of selected ecosystem services in the upper part of the Reventazon watershed and analyzed how supply changed over time in order to identify possible transitions in ecosystem services. The modeled changes of ecosystem services is similar to the second phase of a forest transition but no turning point was identified, probably because of the limited temporal scope of the analysis. Trends of provisioning and regulating services and their tradeoffs were opposite in different spatial subunits of our study area, which highlights the importance of scale in the analysis of ecosystem services and forest transitions. The ecosystem services transition framework proposed in this study is useful for analyzing the temporal changes of ecosystem services and linking socio-economic drivers to ecosystem services demand at different scales. PMID- 27390868 TI - Association of Choline Acetyltransferase Gene Polymorphisms (SNPs rs868750G/A, rs1880676G/A, rs2177369G/A and rs3810950G/A) with Alzheimer's Disease Risk: A Meta-Analysis. AB - BACKGROUND: Epidemiological studies have investigated the role of choline acetyltransferase (ChAT) in Alzheimer's disease (AD). ChAT gene polymorphisms (SNPs rs868750G/A, rs1880676G/A, rs2177369G/A, and rs3810950G/A) may be associated with the risk of AD. In this meta-analysis, we determined the relationship between the four polymorphisms and the risk of AD. METHODS: We searched MEDLINE, EMBASE, and HuGEnet databases for studies linking the four polymorphisms with AD risk. We included 16 articles in our meta-analysis to assess the association between the four polymorphisms and susceptibility to AD by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The combined results showed no significant association with rs1880676G/A and rs2177369G/A polymorphisms. The risk of AD (GG+GA versus AA: OR = 0.01, 95%CI = 0.01-0.02, P < 0.05; GG versus GA+AA: OR = 0.85, 95%CI = 0.72-1.00, P = 0.05; GA versus AA: OR = 0.60, 95% CI = 0.37-0.98, P = 0.04) with rs868750G/A polymorphism, or the association of rs3810950G/A polymorphism with AD risk in the overall population (GA versus AA: OR = 0.64, 95% CI = 0.44-0.93, P = 0.02; GG+GA versus AA: OR = 0.62, 95% CI = 0.39-0.97, P = 0.04) or Asian group (GA versus AA: OR = 0.50, 95% CI = 0.32-0.76, P = 0.001, and GG+GA versus AA: OR = 0.46, 95% CI = 0.30-0.09, P = 0.0002) was demonstrated. CONCLUSIONS: Our meta-analysis suggested that rs1880670G/A, and rs2177369 G/A polymorphisms were not risk factors for AD. However, rs3810950G/A, or rs868750G/A genetic polymorphism was a genetic risk factor for the development of AD. The rs3810950G/A polymorphism had a negative effect on the risk of AD for GA or GG+GA genotypes compared with AA in the overall population or Asians. PMID- 27390870 TI - Wastewater-Enhanced Microbial Corrosion of Concrete Sewers. AB - Microbial corrosion of concrete in sewers is known to be caused by hydrogen sulfide, although the role of wastewater in regulating the corrosion processes is poorly understood. Flooding and splashing of wastewater in sewers periodically inoculates the concrete surface in sewer pipes. No study has systematically investigated the impacts of wastewater inoculation on the corrosion of concrete in sewers. This study investigated the development of the microbial community, sulfide uptake activity, and the change of the concrete properties for coupons subjected to periodic wastewater inoculation. The concrete coupons were exposed to different levels of hydrogen sulfide under well-controlled conditions in laboratory-scale corrosion chambers simulating real sewers. It was evident that the periodic inoculation induced higher corrosion losses of the concrete in comparison to noninoculated coupons. Instantaneous measurements such as surface pH did not reflect the cumulative corrosion losses caused by long-term microbial activity. Analysis of the long-term profiles of the sulfide uptake rate using a Gompertz model supported the enhanced corrosion activity and greater corrosion loss. The enhanced corrosion rate was due to the higher sulfide uptake rates induced by wastewater inoculation, although the increasing trend of sulfide uptake rates was slower with wastewater. Increased diversity in the corrosion layer microbial communities was detected when the corrosion rates were higher. This coincided with the environmental conditions of increased levels of gaseous H2S and the concrete type. PMID- 27390871 TI - MgI2 -chemoselective cleavage for removal of amino acid protecting groups: A fresh vision for peptide synthesis. AB - In the field of peptide synthesis, the key to a successful access to synthetic targets lies on a pertinent combination of protecting groups. Their choice is directed by their selective removal conditions. We present here the behavior of some of the most used protecting groups in peptide chemistry under experimental cleavage conditions, combining MgI2 with MW irradiation, using 2-Me-THF as a green solvent. In these experimental conditions, the benzyloxycarbonyl protecting group as well as the Merrifield resin can be re-considered in peptide chemistry. PMID- 27390872 TI - Correction: Vol. 18, No. 2. PMID- 27390873 TI - The Epipolythiodiketopiperazine Gene Cluster in Claviceps purpurea: Dysfunctional Cytochrome P450 Enzyme Prevents Formation of the Previously Unknown Clapurines. AB - Claviceps purpurea is an important food contaminant and well known for the production of the toxic ergot alkaloids. Apart from that, little is known about its secondary metabolism and not all toxic substances going along with the food contamination with Claviceps are known yet. We explored the metabolite profile of a gene cluster in C. purpurea with a high homology to gene clusters, which are responsible for the formation of epipolythiodiketopiperazine (ETP) toxins in other fungi. By overexpressing the transcription factor, we were able to activate the cluster in the standard C. purpurea strain 20.1. Although all necessary genes for the formation of the characteristic disulfide bridge were expressed in the overexpression mutants, the fungus did not produce any ETPs. Isolation of pathway intermediates showed that the common biosynthetic pathway stops after the first steps. Our results demonstrate that hydroxylation of the diketopiperazine backbone is the critical step during the ETP biosynthesis. Due to a dysfunctional enzyme, the fungus is not able to produce toxic ETPs. Instead, the pathway end products are new unusual metabolites with a unique nitrogen-sulfur bond. By heterologous expression of the Leptosphaeria maculans cytochrome P450 encoding gene sirC, we were able to identify the end-products of the ETP cluster in C. purpurea. The thioclapurines are so far unknown ETPs, which might contribute to the toxicity of other C. purpurea strains with a potentially intact ETP cluster. PMID- 27390875 TI - Are higher doses of proton pump inhibitors better in acute peptic bleeding? AB - Although there is broad consensus about the benefits of proton pump inhibitors in acute upper peptic bleeding, there is still controversy over their optimal dosing. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 27 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded high-dose proton pump inhibitors probably result in little or no difference in re bleeding rate or mortality. The risk/benefit and cost/benefit balance probably favor use of low-doses. PMID- 27390874 TI - Multifunctions of Excited Gold Nanoparticles Decorated Artificial Kidney with Efficient Hemodialysis and Therapeutic Potential. AB - Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificial kidney (AuNPs@AK) for achieving high efficiency accompanying therapeutic strategy for CKD during HD is proposed. The efficiency in removing uremic toxins increased obviously, especially in the presence of protein (closer to the real blood). The excited AuNPs@AK expressed negatively charged surface reduced some acute adverse effects caused by dialysis-induced protein adsorption, platelet adhesion, and activation of coagulation, thus avoiding thrombosis during HD. Unlike to traditional HD which provides only one function of removing uremic toxins, the solution collected from the outlet of the sample channel of excited AuNPs@AK showed an efficient free radical scavenger that could decrease dialysis-induced oxidative stress. In the CKD mouse model, this antioxidative solution from excited AuNPs@AK further decreased fibronectin expression and attenuated renal fibrosis, suggesting a reduced inflammatory response. These successful in vitro and in vivo approaches suggest that resonantly illuminated AuNPs@AK in HD take multiadvantages in shortening treatment time and reducing risk of adverse effects, which promise trailblazing therapeutic strategies for CKD. PMID- 27390876 TI - Replica Exchange Molecular Dynamics Study of Dimerization in Prion Protein: Multiple Modes of Interaction and Stabilization. AB - The pathological forms of prions are known to be a result of misfolding, oligomerization, and aggregation of the cellular prion. While the mechanism of misfolding and aggregation in prions has been widely studied using both experimental and computational tools, the structural and energetic characterization of the dimer form have not garnered as much attention. On one hand dimerization can be the first step toward a nucleation-like pathway to aggregation, whereas on the other hand it may also increase the conformational stability preventing self-aggregation. In this work, we have used extensive all atom replica exchange molecular dynamics simulations of both monomer and dimer forms of a mouse prion protein to understand the structural, dynamic, and thermodynamic stability of dimeric prion as compared to the monomeric form. We show that prion proteins can dimerize spontaneously being stabilized by hydrophobic interactions as well as intermolecular hydrogen bonding and salt bridge formation. We have computed the conformational free energy landscapes for both monomer and dimer forms to compare the thermodynamic stability and misfolding pathways. We observe large conformational heterogeneity among the various modes of interactions between the monomers and the strong intermolecular interactions may lead to as high as 20% beta-content. The hydrophobic regions in helix-2, surrounding coil regions, terminal regions along with the natively present beta-sheet region appear to actively participate in prion-prion intermolecular interactions. Dimerization seems to considerably suppress the inherent dynamic instability observed in monomeric prions, particularly because the regions of structural frustration constitute the dimer interface. Further, we demonstrate an interesting reversible coupling between the Q160-G131 interaction (which leads to inhibition of beta-sheet extension) and the G131-V161 H-bond formation. PMID- 27390877 TI - Treatment experience and long-term follow-up data in two severe neonatal hyperparathyroidism cases. AB - The calcium sensing receptor (CASR) is expressed most abundantly in the parathyroid glands and the kidney. CASR regulates calcium homeostasis through its ability to modulate parathormone secretion and renal calcium reabsorption. Inactivating mutations in the CASR gene may result in disorders of calcium homeostasis manifesting as familial benign hypocalciuric hypercalcemia (FBHH) and neonatal severe hyperparathyroidsm (NSHPT). Two cases were referred with severe hypercalcemia in the neonatal period. Laboratory evaluation revealed severe hypercalcemia and elevated PTH. The parents also had mild hypercalcemia. The serum calcium level did not normalize with conventional hypercalcemia treatment and there was also no response to cinacalcet in case 1. Total parathyroidectomy was performed when the patient was 70 days old. Genetic analysis revealed a novel homozygous p.Arg544* mutation in the CASR gene. Case 2 underwent total parathyroidectomy and autoimplantation when she was 97 days old, but the parathyroid gland implanted into the forearm was removed 27 days later because the hypercalcemia continued. Genetic evaluation revealed a novel homozygous p.Pro682Leu mutation with normal anthropometric measurements. The neurological development is consistent with age in both cases while case 2 has mild mental retardation. No bone deformity or fracture is present in either case and normocalcemia is ensured with calcitriol in both cases. PMID- 27390878 TI - Microarray analysis of slipped capital femoral epiphysis growth plates. AB - BACKGROUND: Microarray technology has been used to analyze gene expression in patients with and without slipped capital femoral epiphysis (SCFE). METHODS: Proximal femoral physis core biopsies from two patients with SCFE were compared with two control specimens from age-matched patients without SCFE. Extracted RNA from frozen ground samples was subjected to microarray analysis with data tests for statistical significance between SCFE and control tissues. RESULTS: Compared to controls, SCFE samples demonstrated significant up-regulation in gene expression pathways involving physiological defense and inflammatory responses and significant down-regulation in the regulation of cellular physiologic processes, cellular metabolic pathways, and skeletal development pathways including expression of aggrecan and type II collagen, genes affecting physeal structure and integrity. CONCLUSIONS: Up-regulation of inflammatory and immune response pathways in SCFE compared to controls relates to physeal mechanical displacement in SCFE. Globalized down-regulation of several other pathways suggests growth plate weakening. These novel microarray findings further define SCFE etiology. PMID- 27390879 TI - Percentiles for anthropometric measures in Iranian children and adolescents: the CASPIAN-IV study. AB - BACKGROUND: The aim of the study was to provide the age- and sex-specific percentile values of anthropometric measures for Iranian children and adolescents. METHODS: This cross-sectional nationwide survey was conducted on a representative sample of 14,880 school students, selected by multistage random cluster sampling from urban and rural areas of 30 provinces in Iran. Anthropometric measures including body mass index (BMI), waist circumference (WC), hip circumference (HC), and wrist circumference were measured under standard protocols by using calibrated instruments. Age- and gender-specific reference values were developed for anthropometric measures by the maximum penalized likelihood approach [Cole's least mean square (LMS) method]. RESULTS: In the present study, 13,486 out of the 14,880 invited subjects completed all the required data of the study (participation rate: 90.6%). Participants consisted of 6640 girls (49.2%) and 75.6% urban residents; their mean and standard deviation (SD) age was 12.47+/-3.36 years. The BMI percentile curves of girls had a sharp increase from 14 to 18 years, and then began to plateau, but among boys, these curves had a consistent increase until the age of 18 years. In addition, the higher percentiles were higher in adolescent boys than girls. The HC percentile curves of both sexes had a persistent increase and the percentiles for HC were higher in adolescent girls than in boys. WC had a sharp increase from 7 to 18 years of age for boys, whereas for girls, these curves had a less sharp increase with age. In all ages, the percentiles for wrist circumference were higher in adolescent boys than girls. CONCLUSIONS: The findings of this study highlight the necessity of paying special attention to developing age- and gender-specific percentiles of anthropometric measures in children and adolescents. PMID- 27390880 TI - Ferritin level is associated with metabolic syndrome and elevated alanine aminotransferase in children and adolescents. AB - BACKGROUND: The aim of the study was to investigate the association among elevated serum ferritin, metabolic syndrome (MetS) and 'elevated alanine aminotransferase (ALT) levels beyond healthy-range limits' in children and adolescents. METHODS: We analyzed data from 4855 subjects (2579 male) aged 10-19 who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007-2012). RESULTS: The prevalence of MetS and 'elevated ALT' tended to increase with an increase in the serum ferritin quartile (p-value for trend: all <0.05). The odds ratios (ORs) for MetS in serum ferritin quartile-Q4 compared to ferritin quartile-Q1 was 1.59 (1.01, 2.55) in females after adjusting for age, body mass index (BMI), and insulin resistance. The ORs for 'elevated ALT' in ferritin quartile-Q4 compared to ferritin quartile-Q1 were 4.45 (2.18, 9.10) in male and 3.10 (1.70, 5.66) in female subjects after adjusting for other covariates. CONCLUSIONS: The independent association between elevated serum ferritin and MetS (or 'elevated ALT') begins in children and adolescents. PMID- 27390881 TI - Membrane trafficking and proteolytic activity of gamma-secretase in Alzheimer's disease. AB - gamma-Secretase is an intramembrane-cleaving protease that generates various forms of amyloid-beta peptides (Abeta) that accumulate in the brains of Alzheimer's disease (AD) patients. The intracellular trafficking and subcellular localization of gamma-secretase are linked to both qualitative and quantitative changes in Abeta production. However, the precise intracellular localization of gamma-secretase as well as its detailed regulatory mechanisms have remained elusive. Recent genetic studies on AD provide ample evidence that alteration of the subcellular localization of gamma-secretase contributes to the pathogenesis of AD. Here we review our current understanding of the intracellular membrane trafficking of gamma-secretase, the association between its localization and proteolytic activity, and the possibility of gamma-secretase as a therapeutic target against AD. PMID- 27390882 TI - Retraction: "Fine- Needle Aspiration Biopsy (FNAB) in the Diagnosis of Pancreatic Adenocarcinoma: A Review" and "Fine Needle Aspiration Biopsy (FNAB) in the Diagnosis of Hepatocellular Carcinoma: A Review.' PMID- 27390883 TI - Extending the Use of the SCORS-G Composite Ratings in Assessing Level of Personality Organization. AB - The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011 ; Westen, 1995b ) reliably measures the quality of object relations in narrative material. It assesses 8 dimensions (on a continuum from maladaptive to adaptive) that mediate interpersonal functioning. The 8 dimensions can be averaged to create a global or composite score to represent a person's overall object relational functioning. This study aimed to create levels of personality organization using the SCORS-G global score ratings of Thematic Apperception Test (TAT) narratives and to explore the construct validity of these levels using a multimethod approach (i.e., psychopathology, normal personality, and life-event data). Meaningful relationships were found between the SCORS-G level of personality organization and aspects of psychopathology (Personality Assessment Inventory; Morey, 1991 ), regulation and control (NEO Five-Factor Inventory; Costa & McCrae, 1989, 1992b ), and number of psychiatric hospitalizations, suicide attempts, and educational level. Overall, this study demonstrates the potential value of creating levels of personality organization (LPO) using the SCORS-G composite or global ratings as a supplement to the psychological assessment process and further highlights the utility of this measure in the field of personality assessment. Clinical and research-related implications as well as limitations are discussed. PMID- 27390884 TI - Editorial. PMID- 27390885 TI - The Unique Gas-Phase Chemistry of the [AuO](+) /CH4 Couple: Selective Oxygen-Atom Transfer to, Rather than Hydrogen-Atom Abstraction from, Methane. AB - The thermal reaction of [AuO](+) with methane has been explored using FT-ICR mass spectrometry complemented by high-level quantum chemical calculations. In contrast to the previously studied congener [CuO](+) , and to [AgO](+) , [AuO](+) reacts with CH4 exclusively via oxygen-atom transfer to form CH3 OH, and a novel mechanistic scenario for this selective oxidation process has been revealed. Also, the origin of the inertness of the [AgO](+) /CH4 couple has been addressed computationally. PMID- 27390886 TI - Biofilm formation of periodontal pathogens on hydroxyapatite surfaces: Implications for periodontium damage. AB - Biofilm formation of periodontal pathogens on teeth surfaces promotes the progression of periodontal disease. Hence, understanding the mechanisms of bacterial attachment to the dental surfaces may inform strategies for the maintenance of oral health. Although hydroxyapatite (HA) is a major calcium phosphate component of teeth, effect of biofilm formation on HA surfaces remains poorly characterized. In this study, biofilm-forming abilities by the periodontal pathogens Aggregatibacter actinomycetemcomitans Y4 and Porphyromonas gingivalis 381 were investigated on dense and porous HAs that represent enamel and dentin surfaces, respectively. These experiments showed greater biofilm formation on porous HA, but differing attachment profiles and effects of the two pathogens. Specifically, while the detachment of A. actinomycetemcomitans Y4 biofilm was observed, P. gingivalis 381 biofilm increased with time. Moreover, observations of HA morphology following formation of A. actinomycetemcomitans Y4 biofilm revealed gaps between particles, whereas no significant changes were observed in the presence of P. gingivalis 381. Finally, comparisons of calcium leakage showed only slight differences between bacterial species and HA types and may be masked by bacterial calcium uptake. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2873-2880, 2016. PMID- 27390887 TI - Rovibrational transitions of the methane-water dimer from intermolecular quantum dynamical computations. AB - Rovibrational quantum nuclear motion computations, with J = 0, 1, and 2, are reported for the intermolecular degrees of freedom of the methane-water dimer, where J is the quantum number describing the overall rotation of the complex. The computations provide the first explanation of the far-infrared spectrum of this complex published in J. Chem. Phys., 1994, 100, 863. All experimentally reported rovibrational transitions, up to J = 2, can be assigned to transitions between the theoretically computed levels. The deviation of the experimental and computed rovibrational transitions is 0.5 cm(-1) for the ortho and 2 cm(-1) for the para species with a variance of 0.005 cm(-1). In addition to a lower systematic error, the overall agreement of theory and experiment is also better for the ortho species (involving ortho-H2O). Most importantly, for this species all levels of the 24-fold tunneling splitting manifold corresponding to the zero-point vibration (ZPV) are involved in at least one experimentally reported transition. For the para species there are a few energy levels in the computed ZPV manifold that are not involved in the reported experimental transitions. Furthermore, computed energy levels are identified that correspond to the ZPV tunneling splitting manifold of the secondary minimum structure of the dimer, which presumably appear in rovibrational transitions in the same energy regime as the observed transitions, but have not been experimentally reported. PMID- 27390888 TI - A D+ blood donor with a novel RHD*D-CE(5-6)-D gene variant exhibits the low frequency antigen RH23 (D(W) ) characteristic of the partial DVa phenotype. AB - BACKGROUND: Blood donors whose red blood cells (RBCs) exhibit a partial RhD phenotype, lacking some D epitopes, present as D+ in routine screening. Such phenotypes can exhibit low-frequency antigens (LFAs) of clinical significance. The aim of this study was to describe the serologic and genetic profile for a blood donor with an apparent D+ phenotype carrying a variant RHD gene where D Exons 5 and 6 are replaced by RHCE Exon (5-6). STUDY DESIGN AND METHODS: Anti-D monoclonal antibodies were used to characterize the presentation of RhD epitopes on the RBCs. RHD exon scanning and DNA sequencing of short- and long-range polymerase chain reaction amplicons were used to determine the RHD structure and sequence. Extended phenotyping for LFAs RH23 (D(W) ) and Rh32 was performed. RESULTS: The donor serology profile was consistent with partial RhD epitope presentation. The donor was hemizygous for an RHD variant allele described as RHD*D-CE(5-6)-D hybrid. The RHCE gene insert is at least 3.868 kb with 5' and 3' breakpoints between IVS4 + 132-c.667 and IVS6 + 1960-IVS6 + 2099, respectively. The sequence for this hybrid was assigned GenBank Accession Number KT099190.2. The RBCs were RH23 (D(W) )+ and Rh32-. CONCLUSION: A novel RHD*D-CE(5-6)-D hybrid allele encodes a partial RhD epitope and carries the LFA RH23 (D(W) ). This and the epitope profile resemble the partial DVa phenotype. Given that RBCs from this individual lack some RhD epitopes, there is an alloimmunization risk if the donor is exposed to D+ RBCs. Conversely, transfusions of RH23 (D(W) )+ cells to RH23 (D(W) )- recipients also pose an alloimmunization risk. PMID- 27390889 TI - Light Makes a Surface Banana-Bond Split: Photodesorption of Molecular Hydrogen from RuO2(110). AB - The coordination of H2 to a metal center via polarization of its sigma bond electron density, known as a Kubas complex, is the means by which H2 chemisorbs at Ru(4+) sites on the rutile RuO2(110) surface. This distortion of electron density off an interatomic axis is often described as a 'banana-bond.' We show that the Ru-H2 banana-bond can be destabilized and split using visible light. Photodesorption of H2 (or D2) is evident by mass spectrometry and scanning tunneling microscopy. From time-dependent density functional theory, the key optical excitation splitting the Ru-H2 complex involves an interband transition in RuO2 which effectively diminishes its Lewis acidity, thereby weakening the Kubas complex. Such excitations are not expected to affect adsorbates on RuO2 given its metallic properties. Therefore, this common thermal cocatalyst employed in photocatalysis is, itself, photoactive. PMID- 27390890 TI - Aberrant podocyte cell cycle in glomerular disease. PMID- 27390891 TI - Computational challenges in modeling gene regulatory events. AB - Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology. PMID- 27390893 TI - Interaction of Lysozyme with Rhodamine B: A combined analysis of spectroscopic & molecular docking. AB - The interaction of Rhodamine B (RB) with Lysozyme (Lys) was investigated by different optical spectroscopic techniques such as absorption, fluorescence, and circular-dichroism (CD), along with molecular docking studies. The fluorescence results (including steady-state and time-resolved mode) revealed that the addition of RB effectively causes strong quenching of intrinsic fluorescence in Lysozyme and mostly, by the static quenching mechanism. Different binding and thermodynamic parameters were calculated at different temperatures and the binding constant value was found to be 2963.54Lmol(-1) at 25 degrees C. The average distance (r0) was found to be 3.31nm according to Forster's theory of non radiative energy transfer between Lysozyme and RB. The conformational change in Lysozyme during interaction with RB was confirmed from absorbance, synchronous fluorescence, and circular dichroism measurements. Finally, molecular docking studies were done to confirm that the dye binds with Lysozyme. PMID- 27390892 TI - Production of superoxide from photosystem II-light harvesting complex II supercomplex in STN8 kinase knock-out rice mutants under photoinhibitory illumination. AB - When phosphorylation of Photosystem (PS) II core proteins is blocked in STN8 knock-out mutants of rice (Oryza sativa) under photoinhibitory illumination, the mobilization of PSII supercomplex is prevented. We have previously proposed that more superoxide (O2(-)) is produced from PSII in the mutant (Nath et al., 2013, Plant J. 76, 675-686). Here, we clarify the type and site for the generation of reactive oxygen species (ROS). Using both histochemical and fluorescence probes, we observed that, compared with wild-type (WT) leaves, levels of ROS, including O2(-) and hydrogen peroxide (H2O2), were increased when leaves from mutant plants were illuminated with excess light. However, singlet oxygen production was not enhanced under such conditions. When superoxide dismutase was inhibited, O2(-) production was increased, indicating that it is the initial event prior to H2O2 production. In thylakoids isolated from WT leaves, kinase was active in the presence of ATP, and spectrophotometric analysis of nitrobluetetrazolium absorbance for O2(-) confirmed that PSII-driven superoxide production was greater in the mutant thylakoids than in the WT. This contrast in levels of PSII-driven superoxide production between the mutants and the WT plants was confirmed by conducting protein oxidation assays of PSII particles from osstn8 leaves under strong illumination. Those assays also demonstrated that PSII-LHCII supercomplex proteins were oxidized more in the mutant, thereby implying that PSII particles incur greater damage even though D1 degradation during PSII-supercomplex mobilization is partially blocked in the mutant. These results suggest that O2(-) is the major form of ROS produced in the mutant, and that the damaged PSII in the supercomplex is the primary source of O2(-). PMID- 27390894 TI - Large in-frame intragenic deletion of OPHN1 in a male patient with a normal intelligence quotient score. PMID- 27390895 TI - Exposure to a heat wave under food limitation makes an agricultural insecticide lethal: a mechanistic laboratory experiment. AB - Extreme temperatures and exposure to agricultural pesticides are becoming more frequent and intense under global change. Their combination may be especially problematic when animals suffer food limitation. We exposed Coenagrion puella damselfly larvae to a simulated heat wave combined with food limitation and subsequently to a widespread agricultural pesticide (chlorpyrifos) in an indoor laboratory experiment designed to obtain mechanistic insights in the direct effects of these stressors in isolation and when combined. The heat wave reduced immune function (activity of phenoloxidase, PO) and metabolic rate (activity of the electron transport system, ETS). Starvation had both immediate and delayed negative sublethal effects on growth rate and physiology (reductions in Hsp70 levels, total fat content, and activity levels of PO and ETS). Exposure to chlorpyrifos negatively affected all response variables. While the immediate effects of the heat wave were subtle, our results indicate the importance of delayed effects in shaping the total fitness impact of a heat wave when followed by pesticide exposure. Firstly, the combination of delayed negative effects of the heat wave and starvation, and the immediate negative effect of chlorpyrifos considerably (71%) reduced larval growth rate. Secondly and more strikingly, chlorpyrifos only caused considerable (ca. 48%) mortality in larvae that were previously exposed to the combination of the heat wave and starvation. This strong delayed synergism for mortality could be explained by the cumulative metabolic depression caused by each of these stressors. Further studies with increased realism are needed to evaluate the consequences of the here-identified delayed synergisms at the level of populations and communities. This is especially important as this synergism provides a novel explanation for the poorly understood potential of heat waves and of sublethal pesticide concentrations to cause mass mortality. PMID- 27390897 TI - Functional Toll-Like Receptor 9 Expression and CXCR3 Ligand Release in Pulmonary Sarcoidosis. AB - Sarcoidosis is a granulomatous disease characterized by a T-helper type 1 (Th1) cell-dominated alveolitis. As a role of bacteria in the pathogenesis of sarcoidosis has been discussed, Toll-like receptors (TLRs) may be involved in the initiation of a first immune reaction. We analyzed expression and functional relevance of several TLRs in bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis. In parallel, we determined the release of C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 by BAL cells from patients with pulmonary sarcoidosis. Nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2, TLR2, TLR6, and TLR9 expression by BAL cells was analyzed by real-time RT PCR and cell surface expression by flow cytometry. Chemokine release was measured in BAL cell culture supernatants by ELISA. We found increased TLR9 mRNA expression in patients with sarcoidosis with chest X-ray type I and II and TLR9 protein expression in BAL cells from patients with chest X-ray type II and III. Stimulation with CpG nucleotides increased CXCL10 release by BAL cells from patients with sarcoidosis type II significantly compared with control subjects or other patients with sarcoidosis. In contrast, no increase in TNF, IL-12p40, or CXCL8 was detected. Spontaneous release of CXCL10, but not CXCL9 or CXCL11, by cultured BAL cells was also highest in cells from patients with chest X-ray type II. We found a significant association between TLR9 expression and CD4+ lymphocytes in BAL. Our data demonstrate that TLR9 ligands may contribute to the immunopathogenesis of sarcoidosis via induction of CXCL10 release in the alveolar macrophages. PMID- 27390896 TI - Targeting recognition surfaces on natural proteins with peptidic foldamers. AB - Molecules intended to antagonize protein-protein interactions or augment polypeptide-based signaling must bind tightly to large and specific surfaces on target proteins. Some types of unnatural oligomers with discrete folding propensities ('foldamers') have recently been shown to display this capability. This review covers important recent advances among several classes of foldamers, including alpha-peptides with secondary structures stabilized by covalent bonds, d-alpha-peptides, alpha/beta-peptides and oligo-oxopiperazines. Recent advances in this area have involved enhancing membrane permeability to provide access to intracellular protein targets, improving pharmacokinetics and duration of action in vivo, and developing strategies appropriate for targeting large and irregularly-shaped protein surfaces. PMID- 27390903 TI - Brain training: hype or hope? AB - Brain training is topical yet controversial. Effects are often limited to trained tasks; and near and far effects to untrained tasks or everyday life measures are often small or lacking altogether. More recent approaches use evidence from cognitive neuroscience on neuroplasticity, resulting in novel cognitive interventions. This special issue encompasses the state of the art of these interventions. Two systematic reviews and nine experimental studies in a variety of patient groups or healthy participants are included, the results of which mostly confirm earlier findings: effects on trained tasks are consistently reported, but generalisation in terms of functional outcome is limited and little evidence is found of long-term effects. In general, the studies show promising, yet challenging training effects on cognition in healthy persons and patients with cognitive deficits. As such, they may be seen as positive "proof of principle" studies, highlighting that cognitive enhancement is possible. The field of brain training, however, is in urgent need of larger and more thoroughly designed studies. These future studies should also include outcome measures on daily functioning, self-efficacy and quality of life in addition to neuropsychological tests or tasks related to cognitive functioning. PMID- 27390907 TI - Total Synthesis of the Hamigerans. AB - The first total synthesis of hamigerans D, G, L, and N-Q has been accomplished. A convergent approach was used to build the basic tricarbocyclic ring system bearing a 5-6-6 structure. A sequence of oxidative cleavage, homologation, and ring regeneration provided access to the 5-7-6 skeleton of hamigeran G. Based on the biogenetic hypothesis, elegant and highly efficient biomimetic transformations of hamigeran G into hamigerans D, N-Q, and L were achieved. PMID- 27390906 TI - Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients. AB - Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log transformed plasma DMP1 levels. Lateral lumbar spine radiographs were used for measurement of vascular calcification. Major cardiovascular events were compared between the two groups. A Cox proportional hazards analysis determined DMP1 was independently associated with cardiovascular outcomes. In vitro mouse osteocytes were cultured in media containing indoxyl sulfate (IS), and the expressions of DMP1 were examined. The mean age was 52.1 +/- 11.8 years, and 116 (52.0%) patients were male. The median value of log DMP1 was 0.91 (0.32-2.81 ng/mL). The multiple logistic regression analysis indicated that DMP1 levels were independently associated with the presence of vascular calcification after adjustment for multiple confounding factors (odds ratio = 0.719; 95% confidence interval [CI] 0.522-0.989; p = 0.043). During a mean follow-up duration of 34.6 months, incident cardiovascular events were observed in 41 (18.4%) patients. A Kaplan-Meier plot showed that the low DMP1 group had a significantly higher rate of incident cardiovascular events compared with the high DMP1 group (log-rank test, p = 0.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio = 0.855; 95% CI 0.743-0.984; p = 0.029) after adjustment for multiple confounding factors. In IS-stimulated osteocytes, mRNA and protein expression levels of DMP1 were significantly decreased compared with control osteocytes. We showed that low DMP1 levels were significantly associated with presence of vascular calcification and were independently associated with the incident cardiovascular events in prevalent peritoneal dialysis patients. DMP1 might be a potential factor contributing to cardiovascular complications in dialysis patients. (c) 2016 American Society for Bone and Mineral Research. PMID- 27390908 TI - Applications of Convertible Isonitriles in the Ligation and Macrocyclization of Multicomponent Reaction-Derived Peptides and Depsipeptides. AB - Peptide ligation and macrocyclization are among the most relevant approaches in the field of peptide chemistry. Whereas a variety of strategies relying on coupling reagents and native chemical ligation are available, there is a continuous need for efficient peptide ligation and cyclization methods. Herein we report on the utilization of convertible isonitriles as effective synthetic tools for the ligation and macrocyclization of peptides arising from isocyanide-based multicomponent reactions. The strategy relies on the use of convertible isonitriles-derived from Fukuyama amines-and peptide carboxylic acids in Ugi and Passerini reactions to afford N-alkylated peptides and depsipeptides, respectively, followed by conversion of the C-terminal amide onto either N peptidoacyl indoles or pyrroles. Such activated peptides proved efficient in the ligation to peptidic, lipidic and fluorescently labeled amines and in macrocyclization protocols. As a result, a wide set of N-substituted peptides (with methyl, glycosyl and amino acids as N-substituents), cyclic N-methylated peptides and a depsipeptide were produced in good yields using conditions that involve either classical heating or microwave irradiation. This report improves the repertoire of peptide covalent modification methods by exploiting the synthetic potential of multicomponent reactions and convertible isonitriles. PMID- 27390910 TI - Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection. AB - In cancer immunotherapy, robust and efficient activation of cytotoxic CD8(+) T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8(+) T cells that kill their target cells directly as well as secrete IFN-gamma, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection in vivo. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to naive CD8(+) T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8(+) T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8(+) T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8(+) T cells that actively produce both intracellular and secretory IFN-gamma were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases. PMID- 27390909 TI - Rendomab B4, a monoclonal antibody that discriminates the human endothelin B receptor of melanoma cells and inhibits their migration. AB - Metastatic melanoma is an aggressive cancer with a poor prognostic, and the design of new targeted drugs to treat melanoma is a therapeutic challenge. A promising approach is to produce monoclonal antibodies (mAbs) against the endothelin B receptor (ETB), which is known to be overexpressed in melanoma and to contribute to proliferation, migration and vasculogenic mimicry associated with invasiveness of this cancer. We previously described rendomab-B1, a mAb produced by DNA immunization. It is endowed with remarkable characteristics in term of affinity, specificity and antagonist properties against human ETB expressed by the endothelial cells, but, surprisingly, had poor affinity for ETB expressed by melanoma cells. This characteristic strongly suggested the existence of a tumor-specific ETB form. In the study reported here, we identified a new mAb, rendomab-B4, which, in contrast to rendomab-B1, binds ETB expressed on UACC 257, WM-266-4 and SLM8 melanoma cells. Moreover, after binding to UACC-257 cells, rendomab-B4 is internalized and colocalizes with the endosomal protein EEA-1. Interestingly, rendomab-B4, despite its inability to compete with endothelin binding, is able to inhibit phospholipase C pathway and migration induced by endothelin. By contrast, rendomab-B4 fails to decrease ERK1/2 phosphorylation induced by endothelin, suggesting a biased effect on ETB. These particular properties make rendomab-B4 an interesting tool to analyze ETB-structure/function and a promising starting point for the development of new immunological tools in the field of melanoma therapeutics. PMID- 27390911 TI - Biochemical basis of sulphenomics: how protein sulphenic acids may be stabilized by the protein microenvironment. AB - Among protein residues, cysteines are one of the prominent candidates to ROS mediated and RNS-mediated post-translational modifications, and hydrogen peroxide (H2 O2 ) is the main ROS candidate for inducing cysteine oxidation. The reaction with H2 O2 is not common to all cysteine residues, being their reactivity an utmost prerequisite for the sensitivity towards H2 O2 . Indeed, only deprotonated Cys (i.e. thiolate form, ?S- ) can react with H2 O2 leading to sulphenic acid formation (?SOH), which is considered as a major/central player of ROS sensing pathways. However, cysteine sulphenic acids are generally unstable because they can be further oxidized to irreversible forms (sulphinic and sulphonic acids, ?SO2 H and ?SO3 H, respectively), or alternatively, they can proceed towards further modifications including disulphide bond formation (?SS?), S glutathionylation (?SSG) and sulphenamide formation (?SN?). To understand why and how cysteine residues undergo primary oxidation to sulphenic acid, and to explore the stability of cysteine sulphenic acids, a combination of biochemical, structural and computational studies are required. Here, we will discuss the current knowledge of the structural determinants for cysteine reactivity and sulphenic acid stability within protein microenvironments. PMID- 27390916 TI - Overall Survival in Spine Myeloma Metastases: Difficulties in Predicting With Prognostic Scores. AB - STUDY DESIGN: Fifty-one patients with spinal multiple myeloma (MM) metastases were operated and followed between January 2004 and July 2014. OBJECTIVE: The aim of this study was to consider the efficiency of surgical prognosis scores in the management of spinal metastases myelomas. SUMMARY OF BACKGROUND DATA: The spine is the most common site of bone metastases in MM. Surgery in spine metastases MM is a matter of debate and its impact on the increase of a patient's survival time is not clear. Several surgical survival scores have been developed to determine the best treatment in these patients. METHODS: We studied 51 patients operated for spinal MM metastases between January 2004 and July 2014. We determined the Tokuhashi and Tomita survival scores and compared them with documented patient survivals. The two scores were also compared with the International Staging System (ISS). RESULTS: Median survival (MS) was 108 months [standard deviation (SD) 62] for ISS I, 132.2 (SD 40) for ISS II, and 45.5 months (SD 16.3) for ISS III (P = 0.09). According to Tokuhashi survival score, 21 patients (41.2%) will survive <6 months, 6 (11.8%) 6 to 12 months, and 24 (47%) >12 months. According to Tomita et al., 50 patients (98%) will survive >49.9 months and 1 patient (2%) <15 months. Regardless of the ISS grade prognosis, Tokuhashi survival score, and to a lesser extent Tomita score, underestimated the actual survival very significantly [P < 0.0001, Log Rank (Mantel-Cox)]. CONCLUSION: We suggest that spine surgical prognosis scores are not accurate and are not able to predict the survival of patients with spine myeloma metastases. Spine surgeons have to be guided not by the initial ISS stage but rather by spinal instability and neurological status. LEVEL OF EVIDENCE: N/A. PMID- 27390917 TI - Intraoperative Neuromonitoring for Anterior Cervical Spine Surgery: What Is the Evidence? AB - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: The goal of this study was to (i) assess the risk of neurological injury after anterior cervical spine surgery (ACSS) with and without intraoperative neuromonitoring (ION) and (ii) evaluate differences in the sensitivity and specificity of ION for ACSS. SUMMARY OF BACKGROUND DATA: Although ION is used to detect impending neurological injuries in deformity surgery, it's utility in ACSS remains controversial. METHODS: A systematic search of multiple medical reference databases was conducted for studies on ION use for ACSS. Studies that included posterior cervical surgery were excluded. Meta-analysis was performed using the random effects model for heterogeneity. Outcome measure was postoperative neurological injury. RESULTS: The search yielded 10 studies totaling 26,357 patients. The weighted risk of neurological injury after ACSS was 0.64% (0.23-1.25). The weighted risk of neurological injury was 0.20% (0.05-0.47) for ACDFs compared with 1.02% (0.10-2.88) for corpectomies. For ACDFs, there was no difference in the risk of neurological injury with or without ION (odds ratio, 0.726; confidence interval, CI, 0.287-1.833; P = 0.498). The pooled sensitivities and specificities of ION for ACSS are 71% (CI: 48%-87%) and 98% (CI: 92%-100%), respectively. Unimodal ION has a higher specificity than multimodal ION [unimodal: 99% (CI: 97%-100%), multimodal: 92% (CI: 81%-96%), P = 0.0218]. There was no statistically significant difference in sensitivities between unimodal and multimodal [68% vs. 88%, respectively, P = 0.949]. CONCLUSION: The risk of neurological injury after ACSS is low although procedures involving a corpectomy may carry a higher risk. For ACDFs, there is no difference in the risk of neurological injury with or without ION use. Unimodal ION has a higher specificity than multimodal ION and may minimize "subclinical" intraoperative alerts in ACSS. LEVEL OF EVIDENCE: 3. PMID- 27390918 TI - Incidence and Risk Factors of Postoperative Hematoma Requiring Reoperation in Single-level Lumbar Fusion Surgery. AB - STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of the present study was to examine the incidence and risk factors for postoperative hematoma requiring reoperation in patients undergoing single-level lumbar fusion surgery. SUMMARY OF BACKGROUND DATA: Postoperative hematoma can cause devastating neurological consequences after spine surgery. Risk factors for hematoma in specific spine procedures have not been well established. METHODS: A cohort of patients undergoing single-level lumbar fusion surgery was constructed from the 2012 to 2013 American College of Surgeons National Surgical Quality Improvement Program dataset using Current Procedural Terminology codes (22533, 22558, 22612, 22630, and 22633). In cases requiring reoperation within 30 days after initial surgery, postoperative hematoma was identified using the ICD-9 code 998.1. Risk factors for postoperative hematoma were assessed with logistic regression modeling. RESULTS: Of 5280 patients undergoing single-level lumbar fusion surgery, 27 patients (0.5%) developed a postoperative hematoma requiring reoperation for hematoma evacuation. A heightened incidence of postoperative hematoma was found in patients who were smokers (1.0% vs. 0.4% for nonsmokers, P = 0.016) or who had a diagnosis of bleeding disorder (3.8% vs. 0.5% for those without bleeding disorder, P = 0.007). Multivariate logistic regression analysis indicated that the adjusted odds ratios for postoperative hematoma associated with smoking and bleeding disorder were 3.34 (95% confidence interval, 1.15-9.71) and 10.2 (95% confidence interval, 1.9-54.8), respectively. CONCLUSION: Smoking and bleeding disorder appear to be major risk factors for postoperative hematoma requiring reoperation after single-level lumbar fusion surgery. Intervention programs targeting patients with these risk factors are needed to reduce their excess risk of postoperative hematoma. LEVEL OF EVIDENCE: 3. PMID- 27390919 TI - Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening. AB - Protein arginine methyltransferases (PRMTs) represent an emerging target class in oncology and other disease areas. So far, the most successful strategy to identify PRMT inhibitors has been to screen large to medium-size chemical libraries. Attempts to develop PRMT inhibitors using receptor-based computational methods have met limited success. Here, using virtual screening approaches, we identify 11 CARM1 (PRMT4) inhibitors with ligand efficiencies ranging from 0.28 to 0.84. CARM1 selective hits were further validated by orthogonal methods. Two structure-based rounds of optimization produced 27 (SGC2085), a CARM1 inhibitor with an IC50 of 50 nM and more than hundred-fold selectivity over other PRMTs. These results indicate that virtual screening strategies can be successfully applied to Rossmann-fold protein methyltransferases. PMID- 27390920 TI - Open questions in watchful waiting for follicular lymphoma. PMID- 27390921 TI - Characterization of quality of sediments from Paranagua Bay (Brazil) by combined in vitro bioassays and chemical analyses. AB - The present study characterizes the quality of sediments from the Paranagua Estuarine Complex (South Brazil). Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) were determined in sediment samples together with a series of different in vitro bioassays. The fish hepatoma cell line (PLHC-1) was used to determine the presence of cytotoxic compounds and CYP1A- and oxidative stress-inducing agents in sediment extracts. Ovarian microsomal fractions from sea bass (Dicentrarchus labrax) were used to detect the presence of endocrine disrupters that interfered with the synthesis of estrogens (ovarian CYP19). Despite the relatively low levels of pollutants and no evidence of negative effects based on guideline levels, sediments collected close to harbors were enriched with CYP1A-inducing agents and they showed higher cytotoxicity. In contrast, sediments from internal areas inhibited CYP19 activity, which suggests the presence of endocrine disrupters at these sites. Overall, the selected bioassays and the chemistry data led to the identification of potentially impacted areas along the Paranagua Estuarine Complex that would require further action to improve their environmental quality. Environ Toxicol Chem 2017;36:1811-1819. (c) 2016 SETAC. PMID- 27390922 TI - Life cycle responses to health insurance status. AB - This paper studies the lifetime effects of exogenous changes in health insurance coverage (e.g. Medicare, PPACA, termination of employer-provided plans) on the dynamic optimal allocation (consumption, leisure, health expenditures), status (health and wealth), and welfare. We solve, simulate, and structurally estimate a parsimonious life cycle model with endogenous exposure to morbidity and mortality risks, and exogenous health insurance. By varying coverage, we identify the marginal effects of insurance when young and/or when old on allocations, statuses, and welfare. Our results highlight positive effects of insurance on health, wealth and welfare, as well as mid-life substitution away from healthy leisure in favor of more health expenses, caused by peaking wages, and accelerating health issues. PMID- 27390923 TI - Early Expressive Language Skills Predict Long-Term Neurocognitive Outcomes in Cochlear Implant Users: Evidence from the MacArthur-Bates Communicative Development Inventories. AB - PURPOSE: The objective of the present article was to document the extent to which early expressive language skills (measured using the MacArthur-Bates Communicative Development Inventories [CDI; Fenson et al., 2006]) predict long term neurocognitive outcomes in a sample of early-implanted prelingually deaf cochlear implant (CI) users. METHOD: The CDI was used to index the early expressive language skills of 32 pediatric CI users after an average of 1.03 years (SD = 0.56, range = 0.39-2.17) of CI experience. Long-term neurocognitive outcomes were assessed after an average of 11.32 (SD = 2.54, range = 7.08-16.52) years of CI experience. Measures of long-term neurocognitive outcomes were derived from gold-standard performance-based and questionnaire-based assessments of language, executive functioning, and academic skills. RESULT: Analyses revealed that early expressive language skills, collected on average 1.03 years post cochlear implantation, predicted long-term language, executive functioning, and academic skills up to 16 years later. CONCLUSION: These findings suggest that early expressive language skills, as indexed by the CDI, are clinically relevant for identifying CI users who may be at high risk for long-term neurocognitive delays and disturbances. PMID- 27390924 TI - Asymmetric Synthesis of CF3- and Indole-Containing Thiochromanes via a Squaramide Catalyzed Michael-Aldol Reaction. AB - A Michael-aldol reaction of 2-mercaptobenzaldehyde with beta-indole-beta-CF3 enones catalyzed by a squaramide has been realized. The method affords a series of 2-CF3-2-indole-substituted thiochromanes featuring a CF3-containing quaternary stereocenter in excellent yields, diastereoselectivities, and enantioselectivities. PMID- 27390925 TI - First-trimester intervention in twin reversed arterial perfusion sequence: does size matter? AB - OBJECTIVE: To evaluate the outcome of first-trimester intervention (12 + 0 to 14 + 0 weeks of gestation) in pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. METHODS: All monochorionic diamniotic twin pregnancies diagnosed with TRAP sequence that underwent intrafetal laser ablation (IFL) of the feeding vessels before 14 + 0 weeks of gestation at the University of Bonn between 2010 and 2015 were analyzed retrospectively for intrauterine course and outcome. RESULTS: In the study period, 12 pregnancies with TRAP sequence were treated by IFL. Median gestational age at intervention was 13.2 (interquartile range (IQR), 12.6-13.6) weeks. In all cases, one intervention sufficed to disrupt the perfusion of the TRAP twin. There was no case of miscarriage, preterm prelabor rupture of membranes or hemorrhage. In five (41.7%) pregnancies, intrauterine death of the pump twin occurred at a median of 72.0 (IQR, 54.0-90.0; range, 48-96) h after intervention. The remaining seven pregnancies continued uneventfully resulting in birth of a healthy infant at term. A comparison of survivors and non-survivors identified a significant difference in median discordance between crown-rump length (CRL) of the pump twin and upper pole-rump length (URL) of the TRAP twin ((CRL - URL)/CRL ratio, 0.56 vs 0.31; P < 0.05 and URL/CRL ratio, 0.44 vs 0.68; P < 0.05). Survivors were treated at a significantly later gestational age than were non-survivors (median, 13.4 (IQR, 12.9-14.1) vs 12.6 (IQR, 12.5-13.1); P < 0.05). However, none of these parameters independently predicted survival. CONCLUSIONS: Although technically feasible, IFL performed in the first trimester for TRAP sequence is associated with a significant fetal loss rate. Gestational age at intervention, (CRL - URL)/CRL ratio and URL/CRL ratio are potential predictors of pregnancy outcome. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27390926 TI - Delayed entry into HIV care after diagnosis in two specialized care and treatment centres in Cameroon: the influence of CD4 count and WHO staging. AB - BACKGROUND: Delayed entry into HIV care has complicated the challenges faced in sub-Saharan Africa due to the high HIV burden. A clear knowledge of the factors affecting delayed entry will be essential in directing interventions towards reducing delayed entry into HIV care. There exist very limited data on delayed entry in Cameroon despite its relevance; hence this study was conducted to determine the rate of delayed entry and its associated factors in HIV programmes in Cameroon. METHODS: Data used for this study was routine data obtained from the files of HIV patients who were diagnosed between January 1, 2015 and June 30, 2015 at Limbe and Buea regional hospital HIV centers in the South West region of Cameroon. Data analysis was done using SPSS version 20. RESULTS: Of the 223 patients included in the study, nearly one-quarter of patients (22.4 %) delayed to enter HIV care within 3 months. Those who delayed to enter care were less likely to present at first diagnosis (using HIV rapid test) with symptoms such as fever > 1 month (5 % versus 30 %, p = 0.01) and weight loss > 10 % (13 % versus 48 %, p < 0.001). Alcohol consumption, WHO stage and CD4 count levels were also associated with delayed entry in bivariate analysis. In multivariate analysis only CD4 count greater than 500cells/MUl and WHO stages I and II were independently associated with delayed entry into HIV care within 3 months. CONCLUSION: In the South West region of Cameroon, approximately 1 out of 4 patients delay to enter HIV care. This high proportion of patients who delay to enter care correlates to the findings recorded by other studies in sub Saharan Africa. Interventions tackling delayed entry into HIV care might need to be favorably directed towards patients that have high CD4 counts and are at very early WHO clinical stages. PMID- 27390927 TI - Coalition of Oct4A and beta1 integrins in facilitating metastasis in ovarian cancer. AB - BACKGROUND: Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis. METHODS: The expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice. RESULTS: We report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin beta1 expression and associated alpha5 and alpha2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34 and CD31 compared to vector control cell-derived xenografts. CONCLUSION: The expression of Oct4A may be crucial to promote and sustain integrin-mediated extracellular matrix (ECM) remodeling requisite for tumor metastasis in ovarian cancer patients. PMID- 27390928 TI - Mechanistic Study of the Synergistic Antibacterial Activity of Combined Silver Nanoparticles and Common Antibiotics. AB - A combination of silver nanoparticles (AgNPs) and an antibiotic can synergistically inhibit bacterial growth, especially against the drug-resistant bacteria Salmonella typhimurium. However, the mechanism for the synergistic activity is not known. This study chooses four classes of antibiotics, beta lactam (ampicillin and penicillin), quinolone (enoxacin), aminoglycoside (kanamycin and neomycin), and polykeptide (tetracycline) to explore their synergistic mechanism when combined with AgNPs against the multidrug-resistant bacterium Salmonella typhimurium DT 104. Enoxacin, kanamycin, neomycin, and tetracycline show synergistic growth inhibition against the Salmonella bacteria when combined with AgNPs, while ampicillin and penicillin do not. UV-vis and Raman spectroscopy studies reveal that all these four synergistic antibiotics can form complexes with AgNPs, while ampicillin and penicillin do not. The presence of tetracycline enhances the binding of Ag to Salmonella by 21% and Ag(+) release by 26% in comparison to that without tetracycline, while the presence of penicillin does not enhance the binding of Ag or Ag(+) release. This means that AgNPs first form a complex with tetracycline. The tetracycline-AgNPs complex interacts more strongly with the Salmonella cells and causes more Ag(+) release, thus creating a temporal high concentration of Ag(+) near the bacteria cell wall that leads to growth inhibition of the bacteria. These findings agree with the recent findings that Ag(+) release from AgNPs is the agent causing toxicity. PMID- 27390929 TI - The impact of increasing income inequalities on educational inequalities in mortality - An analysis of six European countries. AB - BACKGROUND: Over the past decades, both health inequalities and income inequalities have been increasing in many European countries, but it is unknown whether and how these trends are related. We test the hypothesis that trends in health inequalities and trends in income inequalities are related, i.e. that countries with a stronger increase in income inequalities have also experienced a stronger increase in health inequalities. METHODS: We collected trend data on all cause and cause-specific mortality, as well as on the household income of people aged 35-79, for Belgium, Denmark, England & Wales, France, Slovenia, and Switzerland. We calculated absolute and relative differences in mortality and income between low- and high-educated people for several time points in the 1990s and 2000s. We used fixed-effects panel regression models to see if changes in income inequality predicted changes in mortality inequality. RESULTS: The general trend in income inequality between high- and low-educated people in the six countries is increasing, while the mortality differences between educational groups show diverse trends, with absolute differences mostly decreasing and relative differences increasing in some countries but not in others. We found no association between trends in income inequalities and trends in inequalities in all-cause mortality, and trends in mortality inequalities did not improve when adjusted for rising income inequalities. This result held for absolute as well as for relative inequalities. A cause-specific analysis revealed some association between income inequality and mortality inequality for deaths from external causes, and to some extent also from cardiovascular diseases, but without statistical significance. CONCLUSIONS: We find no support for the hypothesis that increasing income inequality explains increasing health inequalities. Possible explanations are that other factors are more important mediators of the effect of education on health, or more simply that income is not an important determinant of mortality in this European context of high-income countries. This study contributes to the discussion on income inequality as entry point to tackle health inequalities. More research is needed to test the common and plausible assumption that increasing income inequality leads to more health inequality, and that one needs to act against the former to avoid the latter. PMID- 27390930 TI - Challenges and opportunities for ELSI early career researchers. AB - BACKGROUND: Over the past 25 years, there has been growing recognition of the importance of studying the Ethical, Legal and Social Implications (ELSI) of genetic and genomic research. A large investment into ELSI research from the National Institutes of Health (NIH) Human Genomic Project budget in 1990 stimulated the growth of this emerging field; ELSI research has continued to develop and is starting to emerge as a field in its own right. The evolving subject matter of ELSI research continues to raise new research questions as well as prompt re-evaluation of earlier work and a growing number of scholars working in this area now identify themselves as ELSI scholars rather than with a particular discipline. MAIN TEXT: Due to the international and interdisciplinary nature of ELSI research, scholars can often find themselves isolated from disciplinary or regionally situated support structures. We conducted a workshop with Early Career Researchers (ECRs) in Oxford, UK, and this paper discusses some of the particular challenges that were highlighted. While ELSI ECRs may face many of the universal challenges faced by ECRs, we argue that a number of challenges are either unique or exacerbated in the case of ELSI ECRs and discuss some of the reasons as to why this may be the case. We identify some of the most pressing issues for ELSI ECRs as: interdisciplinary angst and expertise, isolation from traditional support structures, limited resources and funding opportunities, and uncertainty regarding how research contributions will be measured. We discuss the potential opportunity to use web 2.0 technologies to transform academic support structures and address some of the challenges faced by ELSI ECRs, by helping to facilitate mentoring and support, access to resources and new accreditation metrics. CONCLUSION: As our field develops it is crucial for the ELSI community to continue looking forward to identify how emerging digital solutions can be used to facilitate the international and interdisciplinary research we perform, and to offer support for those embarking on, progressing through, and transitioning into an ELSI research career. PMID- 27390931 TI - An image database of Drosophila melanogaster wings for phenomic and biometric analysis. AB - BACKGROUND: Extracting important descriptors and features from images of biological specimens is an ongoing challenge. Features are often defined using landmarks and semi-landmarks that are determined a priori based on criteria such as homology or some other measure of biological significance. An alternative, widely used strategy uses computational pattern recognition, in which features are acquired from the image de novo. Subsets of these features are then selected based on objective criteria. Computational pattern recognition has been extensively developed primarily for the classification of samples into groups, whereas landmark methods have been broadly applied to biological inference. RESULTS: To compare these approaches and to provide a general community resource, we have constructed an image database of Drosophila melanogaster wings - individually identifiable and organized by sex, genotype and replicate imaging system - for the development and testing of measurement and classification tools for biological images. We have used this database to evaluate the relative performance of current classification strategies. Several supervised parametric and nonparametric machine learning algorithms were used on principal components extracted from geometric morphometric shape data (landmarks and semi-landmarks). For comparison, we also classified phenotypes based on de novo features extracted from wing images using several computer vision and pattern recognition methods as implemented in the Bioimage Classification and Annotation Tool (BioCAT). CONCLUSIONS: Because we were able to thoroughly evaluate these strategies using the publicly available Drosophila wing database, we believe that this resource will facilitate the development and testing of new tools for the measurement and classification of complex biological phenotypes. PMID- 27390932 TI - Competitive advantage of a dengue 4 virus when co-infecting the mosquito Aedes aegypti with a dengue 1 virus. AB - BACKGROUND: Dengue viruses (DENV) are comprised in four related serotypes (DENV-1 to 4) and are critically important arboviral pathogens affecting human populations in the tropics. South American countries have seen the reemergence of DENV since the 1970's associated with the progressive re-infestation by the mosquito vector, Aedes aegypti. In French Guiana, DENV is now endemic with the co circulation of different serotypes resulting in viral epidemics. Between 2009 and 2010, a predominant serotype change occurred from DENV-1 to DENV-4 suggesting a competitive displacement. The aim of the present study was to evaluate the potential role of the mosquito in the selection of the new epidemic serotype. METHODS: To test this hypothesis of competitive displacement of one serotype by another in the mosquito vector, we performed mono- and co-infections of local Ae. aegypti collected during the inter-epidemic period with both viral autochthonous epidemic serotypes and compared infection, dissemination and transmission rates. We performed oral artificial infections of F1 populations in BSL-3 conditions and analyzed infection, dissemination and transmission rates. RESULTS: When two populations of Ae. aegypti from French Guiana were infected with either serotype, no significant differences in dissemination and transmission were observed between DENV-1 and DENV-4. However, in co-infection experiments, a strong competitive advantage for DENV-4 was seen at the midgut level leading to a much higher dissemination of this serotype. Furthermore only DENV-4 was present in Ae. aegypti saliva and therefore able to be transmitted. CONCLUSIONS: In an endemic context, mosquito vectors may be infected by several DENV serotypes. Our results suggest a possible competition between serotypes at the midgut level in co infected mosquitoes leading to a drastically different transmission potential and, in this case, favoring the competitive displacement of DENV-1 by DENV-4. This phenomenon was observed despite a similar replicative fitness in mono infections conditions. PMID- 27390936 TI - Bilateral axillary artery cannulation for severely calcified aorta and branches: a case report. AB - BACKGROUND: Aortic valve surgery in patients with severely calcified aortas is technically challenging. Additionally, the choice of arterial cannulation site and whether to perform an aortic clamp to prevent neurological complications are poorly defined. CASE PRESENTATION: We describe a patient with a severely calcified aorta and stenosis of its side branches. He successfully underwent aortic valve replacement with bilateral axillary artery cannulation and short term moderate hypothermic circulatory arrest for cross-clamping of a severely calcified aorta to prevent neurological complications. CONCLUSIONS: Bilateral axillary artery cannulation and short-term moderate hypothermic circulatory arrest for cross-clamping of the porcelain aorta is a suitable option to prevent neurological complications in patients with a severely calcified aorta and stenosis of its side branches who need aortic valve replacement. PMID- 27390937 TI - Formation of Sr adatom chains on SrTiO3 (1 1 0) surface determined by strain. AB - The adsorption behavior of Sr adatoms on the SrTiO3 (1 1 0)-(4 * 1) reconstructed surface with Ti2O3 vacancies distributed in a superstructure is studied by scanning tunneling microscopy and density functional theory calculations. With the adsorption amount increasing, all the Sr adatoms between adjacent Ti2O3 vacancies are closely packed along the quasi-1D stripes on the surface with a uniform separation from each other. The formation of such adatom chains is determined by the surface strain relief-the local lattice relaxations in response to Sr adatoms and Ti2O3 vacancies are incompatible, leading to the strong repulsive interaction between them. Consequently the distribution of Sr chains follows the long-range order of the growth template with their length tunable in a certain range by evaporation amount. PMID- 27390933 TI - The Swiss Preschoolers' health study (SPLASHY): objectives and design of a prospective multi-site cohort study assessing psychological and physiological health in young children. AB - BACKGROUND: Children's psychological and physiological health can be summarized as the child's thinking, feeling, behaving, eating, growing, and moving. Children's psychological and physiological health conditions are influenced by today's life challenges: Thus, stress exposure and lack of physical activity represent important health challenges in older children. However, corresponding evidence for young children is scarce. The aim of Swiss Preschoolers' Health Study (SPLASHY) is to examine the role of stress and physical activity on children's psychological and physiological health, particularly on cognitive functioning, psychological well-being, adiposity and motor skills in children at an early stage of childhood. We will also assess the role of child and environmental characteristics and aim to define sensitive time points. METHODS/DESIGN: In a total of 84 child care centers, children at preschool age (2 6 years) are recruited and are assessed immediately and one year later. Assessments include direct measurements of the children in the child care centers and at home as well as assessments of children's behavior and environmental factors through informants (parents and child care educators). DISCUSSION: SPLASHY is one of the first studies in early childhood aiming to investigate the influence of stress and physical activity on children's psychological and physiological health in a community-based longitudinal design. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41045021 (date of registration: 21.03.14). PMID- 27390934 TI - A new genomic library of melon introgression lines in a cantaloupe genetic background for dissecting desirable agronomical traits. AB - BACKGROUND: Genomic libraries of introgression lines (ILs) consist of collections of homozygous lines with a single chromosomal introgression from a donor genotype in a common, usually elite, genetic background, representing the whole donor genome in the full collection. Currently, the only available melon IL collection was generated using Piel de sapo (var. inodorus) as the recurrent background. ILs are not available in genetic backgrounds representing other important market class cultivars, such as the cantalupensis. The recent availability of genomic tools in melon, such as SNP collections and genetic maps, facilitates the development of such mapping populations. RESULTS: We have developed a new genomic library of introgression lines from the Japanese cv. Ginsen Makuwa (var. makuwa) into the French Charentais-type cv. Vedrantais (var. cantalupensis) genetic background. In order to speed up the breeding program, we applied medium throughput SNP genotyping with Sequenom MassARRAY technology in early backcross generations and High Resolution Melting in the final steps. The phenotyping of the backcross generations and of the final set of 27 ILs (averaging 1.3 introgressions/plant and covering nearly 100 % of the donor genome), in three environments, allowed the detection of stable QTLs for flowering and fruit quality traits, including some that affect fruit size in chromosomes 6 and 11, others that change fruit shape in chromosomes 7 and 11, others that change flesh color in chromosomes 2, 8 and 9, and still others that increase sucrose content and delay climacteric behavior in chromosomes 5 and 10. CONCLUSIONS: A new melon IL collection in the Charentais genetic background has been developed. Genomic regions that consistently affect flowering and fruit quality traits have been identified, which demonstrates the suitability of this collection for dissecting complex traits in melon. Additionally, pre-breeding lines with new, commercially interesting phenotypes have been observed, including delayed climacteric ripening associated to higher sucrose levels, which is of great interest for Charentais cultivar breeding. PMID- 27390938 TI - Culprit-lesion only versus complete multivessel percutaneous intervention in ST elevation myocardial infarction: A systematic review and meta-analysis of randomized trials. AB - BACKGROUND: ST-segment elevation myocardial infarction (STEMI) in patients with concomitant multivessel (MV) coronary artery disease (CAD) is associated with poor outcomes. Percutaneous coronary intervention (PCI) of the culprit-lesion only (CLO) as compared with a MV PCI approach to revascularization remains uncertain. Our objective is to gain a better understanding of the efficacy and safety of CLO as compared with MV PCI in patients with STEMI by conducting an updated meta-analysis. METHODS: A comprehensive search of PubMed, CENTRAL, EMBASE, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar databases of randomized controlled trials (RCTs) was performed. RESULTS: Seven RCTs were included, enrolling a total of 2006 patients. We found that there was a significant reduction in major adverse cardiovascular events (MACE) (OR, 0.62; 95% CI, 0.43-0.90), cardiovascular mortality (OR, 0.46; 95% CI, 0.27-0.80), and repeat revascularization (RRV) (OR, 0.39; 95% CI, 0.30-0.51) favoring MV over the CLO approach for patients undergoing primary PCI. The number needed to treat in order to prevent one CV mortality, RRV, or MACE event is 47, 11, and 16 patients, respectively. No differences were observed between MV vs. CLO PCI for subsequent myocardial infarction (OR, 0.74; 95% CI, 0.40-1.39), all-cause mortality (OR, 0.78; 95% CI, 0.53-1.15), non-cardiovascular mortality (OR, 1.35; 95% CI, 0.74-2.48), all-bleeding events (OR, 0.82; 95% CI, 0.40-1.65), contrast induced nephropathy (OR, 0.72; 95% CI, 0.33-1.54), and stroke (OR, 1.28; 95% CI, 0.47-3.46). CONCLUSIONS: MV PCI significantly reduces the rate of MACE, CV mortality, and RRV without significant harm as compared to CLO PCI. PMID- 27390939 TI - Left ventricular diastolic dysfunction and increased left ventricular mass index related to pulmonary hypertension in patients with systemic autoimmune disease without pericardial effusion. AB - PURPOSE: We investigated the relationship of left ventricular (LV) diastolic dysfunction and LV mass index (LVMI) against pulmonary hypertension (PH) in systemic autoimmune disease (SAD). METHODS: A total of 84 SAD patients (68 females; 53+/-17years; systemic lupus erythematosus, 27%; scleroderma, 17%; vasculitis, 16%; mixed connective tissue disease, 13% and polymyositis/dermatomyositis complex, 10%) without significant pericardial effusion (PE) on TTE (Vivid E9, GE) were analyzed. On TTE, PH was defined as peak tricuspid regurgitation velocity (TRV) of >=2.9m/s based upon 2015 ESC guideline. Left atrial volume index (LAVI) and E/E' were measured as indicators of LV diastolic dysfunction. LVMI was also measured. RESULTS: Seven patients (8%) had PH. PH patients had greater LAVI (p<0.001), E/E' (p=0.004), LVMI (p=0.009) than non-PH patients. LAVI (R=0.458), E/E' (R=0.337), and LVMI (R=0.313) significantly and positively correlated with TRV (all p<0.05). Multiple regression analysis was performed to explore determinants of TRV. Age, female sex, and brain natriuretic peptide (BNP) were included in all the models. Three multiple regression models were generated using 1) LAVI, 2) E/E', and 3) LVMI and included LAVI, E/E', LVMI, and BNP as significant variables influencing TRV. Multi logistic regression analysis for predicting TRV of >=2.9m/s showed that LAVI, and E/E' were significant predictors (Odds ratio, 1.296, and 1.370, respectively). CONCLUSION: In SAD patients without PE, LV diastolic dysfunction and increment of LVMI was closely associated with PH based upon TRV. LAVI and E/E' were independent predictors for PH. Measuring LAVI and E/E' may be a key to determine the mechanism of PH in these patients. PMID- 27390940 TI - Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation. AB - BACKGROUND: Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. METHODS: We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). RESULTS: We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. CONCLUSION: Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits. PMID- 27390941 TI - Echocardiography-detected apical pseudohypertrophy and takotsubo syndrome. PMID- 27390942 TI - Cardiac arrest and ventricular fibrillation in a young man treated with capecitabine: Case report and literature review. PMID- 27390943 TI - Uptake of evidence-based statin therapy among atrial fibrillation patients in China: A report from the CAFR (Chinese Atrial Fibrillation Registry) Study. AB - BACKGROUND: Atrial fibrillation (AF) is associated with increased incidence of cardiovascular disease, and hence, statin therapy is indicated in majority of AF patients. METHODS AND RESULTS: We analyzed data from the Chinese Atrial Fibrillation Registry (CAFR) involving 11,496 AF patients from 2011 to 2014. Practice patterns of statin therapy and factors associated with statin underuse were analyzed. Based on the 2013 ACC/AHA cholesterol management guidelines, statins should be recommended for 67.4% (7720/11,461) of AF participants in CAFR, but only 43.4% (3352/7720) with appropriate indications were taking statins. Statin underuse in AF patients was independently associated with male sex, tertiary hospital treatment, outpatient attendance, and absence of 'high risk' cardiovascular risk factors (overweight, diabetes, coronary heart disease, stroke/transient ischemic attack/peripheral embolism and hypertension). CONCLUSIONS: A high proportion of Chinese AF patients had indications for statin therapy. Evidence-based statin prescribing was suboptimal in this population. Greater efforts should be made to improve a holistic approach to cardiovascular risk management in the Chinese AF population. PMID- 27390944 TI - Novel long QT syndrome-associated missense mutation, L762F, in CACNA1C-encoded L type calcium channel imparts a slower inactivation tau and increased sustained and window current. AB - BACKGROUND: Mutations in the CACNA1C-encoded L-type calcium channel have been associated with Timothy syndrome (TS) with severe QT prolongation, syndactyly, facial dysmorphisms, developmental delay, and sudden death. Recently, patients hosting CACNA1C mutations with only long QT syndrome (LQTS) have been described. We sought to identify novel variants in CACNA1C associated with either TS or LQTS, and to determine the impact of the mutation on channel function. METHODS/RESULTS: Two probands were identified with mutations in CACNA1C, one with a TS-associated mutation, G406R, and a second with genotype-negative LQTS. Illumina HiSeq 2000 whole exome sequencing on the genotype-negative LQTS proband revealed a novel variant, CACNA1C-L762F, that co-segregated within a multi generational family. The missense mutation localized to the DII/DIII intracellular interlinker segment of the channel in a highly conserved region in close proximity to the 6th transmembrane segment of domain II (DIIS6). Whole cell patch clamp of heterologously expressed CACNA1C-L762F in TSA201 cells demonstrated slower inactivation tau and increased sustained and window current. Comprehensive review and topological mapping of all described CACNA1C mutations revealed TS-specific hotspots localizing to the cytoplasmic aspect of 6th transmembrane segment of respective domains. Probands hosting TS mutations were associated with elevated QTc, higher prevalence of 2:1 AV block, and a younger age at presentation compared to LQTS. CONCLUSIONS: The CACNA1C-L762F mutation is associated with development of LQTS through slower channel inactivation and increased sustained and window current. TS-associated mutations localize to specific areas of CACNA1C and are associated with a younger age at presentation, higher QTc, and 2:1 AV block than isolated LQTS-associated mutations. PMID- 27390945 TI - Add-on tests for improving risk-stratification in emergency department patients with chest pain who are at low to moderate risk of 30-day major adverse cardiac events. AB - BACKGROUND: Chest pain patients commonly present to emergency departments (ED), and require either hospital admission and/or lengthy diagnostic protocols to rule out myocardial infarction. We aimed to identify the best combination of add-on tests to high-sensitivity cardiac troponin (hs-cTnT) for predicting 30-day major adverse cardiac events (MACE) in adult chest pain patients presenting to an ED with suspected acute coronary syndrome. METHODS: This prospective observational study was conducted in the ED of a tertiary university hospital in Hong Kong, recruiting adult patients with chest pain of less than 24h duration, suspected with acute coronary syndrome (ACS), and had no history of coronary artery bypass grafting or stent insertion. Patients underwent triage assessment, electrocardiography, blood sampling for laboratory hs-cTnT, and Thrombolysis in Myocardial Infarction (TIMI) and HEART score assessment. The primary outcome was the number of patients with 30-day MACE. RESULTS: 602 consecutive patients were recruited and completed 30-day follow-up. A 30-day MACE occurred in 42 (7.0%) patients. Out of 12 possible models for stratifying patients at risk of 30-day MACE within 2h of ED arrival, a combination of electrocardiography (ECG) and one time hs-cTnT (model 5) provided the simplest and most accurate model. A risk score of 0 to 5 was derived from raw coefficients of model 5. The risk score provided excellent calibration (P=0.91) and discrimination (AUC 0.87, 95% CI: 0.82 to 0.93). CONCLUSION: Appropriate early risk-stratification of patients with chest pain and possible ACS using a combination of ECG and one-time hs-cTnT may improve efficiency of care. PMID- 27390946 TI - Is the association of history of psychiatric disorders with takotsubo syndrome partially mediated by the underlying psychotropic drug therapy? PMID- 27390947 TI - Like mother like daughter: A case report of simultaneous mother-daughter Takotsubo cardiomyopathy triggered by a house fire. PMID- 27390948 TI - Roles of Chinese herbal medicines in ischemic heart diseases (IHD) by regulating oxidative stress. AB - Ischemic heart disease (IHD) basing on atherosclerosis (AS) is known as a top killer for decades. Oxidative stress, representing excessive oxidation and insufficient elimination, has been proved to be a critical molecular mechanism of IHD and accompanying myocardium dysfunction. Therefore, anti-oxidation therapy may be efficient. Chinese herbal medicine, including extractive compounds, decoctions, patent drugs, and injections, has shown its enormous potential in prevention and treatment of IHD as an effective antioxidant in experimental studies. The aim of this review is to highlight recent studies of Chinese herbal medicine in regulating oxidative stress in IHD. These studies represent recent progress of IHD treatment and indicate the possible pathways and target spots of Chinese herbal medicine. PMID- 27390949 TI - Worse survival after transcatheter aortic valve implantation than surgical aortic valve replacement: A meta-analysis of observational studies with a propensity score analysis. AB - OBJECTIVES: To determine whether transcatheter aortic valve implantation (TAVI) improves (or impairs) follow-up overall survival compared with surgical aortic valve replacement (SAVR), we performed a meta-analysis of observational studies with a propensity-score analysis and another meta-analysis of randomized controlled trials (RCTs). METHODS: Databases including MEDLINE and EMBASE were searched through October 2015 using PubMed and OVID. Eligible studies were observational studies with a propensity-score analysis or RCTs of TAVI versus SAVR enrolling patients with severe aortic stenosis and reporting follow-up overall survival or all-cause mortality as an outcome. A hazard ratio (HR) with its 95% confidence interval (CI) of follow-up (including early) all-cause mortality for TAVI versus SAVR was abstracted from each individual study. RESULTS: Our search identified 19 observational studies with a propensity-score analysis enrolling a total of 6234 patients. The arithmetic means of 1-year and 3 year survival rates were 82.7% and 71.3% after TAVI and 84.8% and 77.9% after SAVR, respectively. A pooled analysis demonstrated a statistically significant 21% increase in the hazard of mortality with TAVI relative to SAVR (HR, 1.21; 95% CI, 1.05 to 1.39; p=0.010). Another pooled analysis of 4 RCTs (enrolling a total of 1795 patients) demonstrated no statistically significant difference in mortality between TAVI and SAVR (HR, 0.92; 95% CI, 0.62 to 1.37; p=0.69). CONCLUSIONS: The arithmetic mean of 3-year survival rates was 71.3% after TAVI and 77.9% after SAVR. Compared with SAVR, TAVI appears to be associated with a significant increase in follow-up all-cause mortality. PMID- 27390950 TI - Impact of aspirin on the prognosis in patients with coronary spasm without significant atherosclerotic stenosis. AB - BACKGROUND: Coronary spasm is one of the mechanisms of myocardial infarction with nonobstructive coronary arteries (MINOCA). The aim of this study was to investigate the effects of aspirin on future cardiovascular events in patients with coronary vasospastic angina (VSA) with non-significant atherosclerotic stenosis. METHODS: This was the retrospective analysis of the 640 VSA patients with non-significant atherosclerotic stenosis (<=50% stenosis) among 1,877 consecutive patients who underwent acetylcholine (ACh)-provocation testing between January 1991 and December 2010. The patients were divided into 2 groups treated with (n=137) or without (n=503) low-dose aspirin (81-100mg/day). We evaluated major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction, and unstable angina. RESULTS: In the study population, 24 patients (3.8%) experienced MACE; there were 6 cases in VSA patients with aspirin and 6 in those without aspirin. Multivariate Cox hazards analysis for correlated factors of MACE indicated that use of statin (HR: 0.11; 95% CI: 0.02 to 0.84; P=0.033), ST-segment elevation during attack (HR: 5.28; 95% CI: 2.19-12.7; P<0.001), but not the use of aspirin as a significant predictor of MACE. After propensity score matching (n=112, each), Kaplan-Meier survival analysis indicated almost identical rate of 5-year survival free from MACE in those with aspirin, compared to those without aspirin in the entire and matched cohort (P=0.640 and P=0.541, respectively). CONCLUSIONS: Low-dose aspirin might not reduce future cardiovascular events in VSA patients with non-significant stenosis. PMID- 27390951 TI - Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects. AB - BACKGROUND: We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. METHODS: Twenty-seven, 34.6+/-17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. RESULTS: No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. CONCLUSIONS: In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. PMID- 27390952 TI - Atrial septal pouch - Morphological features and clinical considerations. AB - BACKGROUND: The atrial septal pouch (SP) is a new anatomical entity within the interatrial septum. The left-sided SP may be the source of thrombus and contribute to ischemic stroke. The aim of this study was to provide a detailed morphometric description of the SP. METHODS: Two hundred autopsied hearts (23% deriving from females) with a mean age of 46.7+/-19.1years were investigated. We assessed the morphology of the interatrial septum. We obtained measurements and casts of the SPs, and we conducted histological staining of the left-sided SPs. RESULTS: Patent foramen ovale was observed in 25% of hearts. We found a left SP in 41.5%, right in 5.5% and a double SP in 5.5% of hearts. We found the patent foramen ovale (PFO) more often in younger hearts, and the SP and smooth septum were more prevalently found in older hearts (p=.0023). The mean volume of the left-sided SP was 0.31+/-0.11ml, which represented 13.6+/-9.4% (range: 3.1-44.9%) of the left atrial appendage volume. The SP shape resembled a cone or a cylinder with some smaller diverticula originating from the main body. The SP free wall was composed of two layers of endocardium, transverse muscle fibers and connective tissue. CONCLUSIONS: A left-sided SP was present in 47% of individuals. The SP arises as a result of PFO channel closure. The anatomy of left-sided SP may promote blood stasis and thrombus formation. The universal formula for SP volume was calculated. PMID- 27390953 TI - Prognosis after acute coronary syndrome in relation with ventricular-arterial coupling and left ventricular strain. AB - BACKGROUND: The value of modern non-invasive indices of the left ventricle (LV) and arterial system function, and their interaction for determining prognosis in contemporarily treated patients with acute coronary syndrome (ACS) is not well established. The study aimed to determine the association of ventricular-arterial (VA) coupling, LV global longitudinal peak systolic strain (GLPSS), global strain rate (GSR) and end-diastolic volume at end-diastolic pressure 30mmHg (V30) with long-term clinical outcomes in patients with ACS. METHODS: Echocardiography was applied in 569 ACS patients followed up for >12months after hospitalization. Univariate Cox proportional hazard regression models adjusted to various clinical factors, including reduced LV ejection fraction <40%, were used to compare patients between the first and third tertiles of various indices of LV and arterial systems function and their interaction for the prediction of a combined end-point (defined as either stroke, myocardial infarction or death). Results are presented as hazard ratio (HR) with 95% confidence interval (CI). RESULTS: There were 57 clinical outcomes during a median follow-up of 625days. Increased VA coupling >1.68 (HR 2.4; 95% CI: 1.04-5.6); V30>107mL (HR 4.5; 95% CI: 1.9-10.6), GLPSS > -12.8% (HR 2.4; 95% CI: 1.02-5.7), GSR > -0.96 1/s (HR 3.8; 95% CI: 1.6 9.1) were robustly associated with increased hazard. CONCLUSIONS: With a sample of contemporarily treated ACS patients, abnormal values of non-invasive indices of LV function and their interaction with arterial system, predict adverse clinical outcomes, independently of LV ejection fraction. PMID- 27390954 TI - Insulin resistance-associated decreases in left ventricular diastolic function are strongly modified by the extent of concentric remodeling in a community sample. AB - BACKGROUND: Whether excess adiposity, associated metabolic abnormalities or alternative risk factors for left ventricular (LV) diastolic function are modified rather than mediated by geometric LV remodeling, is uncertain. METHODS: Echocardiographic LV mass index (LVMI), relative wall thickness (RWT) and diastolic function (lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus [e'] [n=430], ratio of early-to-late transmitral blood flow velocity (E/A), and E/e' [n=430]) were determined in 737 randomly recruited participants of a community-based study (43% obese). RESULTS: Independent of LVMI and confounders, indexes of adiposity and the homeostasis model of insulin resistance (HOMA-IR) were independently associated with LV diastolic function (p<0.05). In addition, RWT was independently associated with LV diastolic function (p<0.002). Importantly, an independent interaction between HOMA-IR and RWT, but not between blood pressure or age and RWT, was related to LV diastolic function (p<0.05). This translated into an independent relationship between HOMA-IR and lateral e' (partial r=-0.17, p<0.02), septal e' (partial r= 0.14, p=0.05), E/A (partial r=-0.17, p<0.005) and E/e' (partial r=0.19, p<0.01) in those with RWT above, but a lack of relationship between HOMA-IR and LV diastolic function (p>0.59) in those with RWT below the median for the sample. Similarly, HOMA-IR was independently associated with LV diastolic dysfunction in those with RWT above (p<0.05) but not below (p>0.19) the median for the sample. CONCLUSIONS: The relationship between insulin resistance, but not alternative risk factors and LV diastolic function is markedly modified by the presence of a more concentrically remodeled LV. PMID- 27390955 TI - Psychological correlates, allostatic overload and clinical course in patients with implantable cardioverter defibrillator (ICD). AB - BACKGROUND: Implantable cardioverter defibrillator (ICD) is a key treatment option for both primary and secondary prevention of sudden cardiac death. Despite this, there is a growing number of studies showing that ICD is often associated with post-implantation deleterious psychosocial effects, even in the absence of medical complications. Knowledge about the predictive role of pre-ICD psychological profile is scant. The present research aims to describe patients' pre-ICD psychological profile, focusing on acute and chronic distress, such as anxiety, depression, type D personality, psychosomatic syndromes and allostatic overload (AO), and to evaluate if these psychological variables could affect ICD outcomes and survival. METHODS: 117 consecutive patients (74.4% males; mean age=63.1+/-13.7years) underwent psychological assessment prior to ICD implantation. Data on ICD-related complications and death were collected up to 26months after the intervention. RESULTS: At baseline, 36.8% of the sample had anxiety and 17.9% depression. Among psychosomatic syndromes, psychological factors affecting medical conditions were the most frequent (37.6%). 12.8% presented with type D personality, whereas 16.2% showed moderate AO and 4.3% severe AO. 25.6% of the patients had post-ICD complications and 6% died. Severe AO was the only predictor of survival. CONCLUSION: Our findings show that a reliable evaluation of stress and the inability to cope with it (allostatic overload) may help to identify patients at higher risk of post-ICD complications and death. Such sensitive index, more than traditional psychiatric diagnostic criteria, may help the physician to identify easily manifestations of distress and clinically relevant information, which could affect medical illness outcomes. PMID- 27390956 TI - The effect of statin treatment on the prevention of stent mediated flow limited edge dissections during PCI in patients with stable angina. AB - OBJECTIVES: The effect of statin therapy before PCI with direct stenting may reduce the development of flow limited edge dissections (ED) in patients with stable angina. BACKGROUND: Flow limited ED after PCI is associated with an increased risk of major adverse cardiovascular events. Statin therapy induces important changes in the plaque composition which have been previously identified as strong predictors of ED. MATERIAL AND METHODS: 100 patients complicated with flow limited ED and 100 control patients with successful procedure were enrolled into the study. EDs were described as the 5-mm regions that were immediately adjacent to the stent borders, both distally and proximally on the coronary angiography. RESULTS: Rate of statin use and duration of statin use were significantly higher in patients with non-ED group (63%) versus ED group (25%) (p<0.001). In addition, patients in ED group had significantly higher levels of C reactive protein (CRP) at admission (9.9mg/dL (5.89-16.45) vs. 4.40mg/dL (3.5 7.09), respectively, p=0.014). CONCLUSIONS: Our findings suggested that maintenance statin treatment before PCI with direct stenting may reduce the development of flow limited ED in patients with stable angina. PMID- 27390957 TI - Characteristics and long-term outcome of right ventricular involvement in Takotsubo cardiomyopathy. AB - OBJECTIVE: Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy (SCM) resembles a reversible cardiomyopathy that is characterized by localized wall motion abnormalities in the absence of stenotic coronary vascular disease. Patients typically present with apical ballooning of the left ventricle (LV), however the right ventricle (RV) is also affected in up to 50.0% of patients. Long-term prognosis of classical SCM resembles that of patients after ST elevation myocardial infarction. Data on long-term prognosis of biventricular compared to classical SCM is controversial. The aim of this study was therefore to analyze patients with biventricular SCM regarding in-hospital outcome and long term prognosis. MATERIALS AND METHODS: 114 consecutive patients with SCM were retrospectively analyzed. 88 patients presented with classical SCM, 26 patients (22.8%) were diagnosed with biventricular SCM. Follow-up was conducted for a total of 4.4years. Mean age was 67.1years with 83.3% of patients being female. The primary endpoint was a composite of all-cause mortality, recurrence of SCM and re-hospitalization due to heart failure. RESULTS: Although patients with biventricular SCM presented with a tendency towards an increased rate of cardiogenic shock (30.8% vs. 15.9%; p=0.09) and significantly more usage of inotropic support upon hospital admission (34.6% vs. 13.6%; p=0.01), there was no difference concerning the primary endpoint in both groups (50.0% vs. 44.3%; p=0.31). Furthermore, there was no difference in mortality both in-hospital (7.7% vs. 7.9%; p=0.66) and during long-term follow-up (27.3% vs. 23.1%; p=0.46). CONCLUSION: Patients with biventricular SCM have the same in-hospital and long term outcome compared to classical SCM. PMID- 27390958 TI - Renal tubular damage is associated with poor clinical outcome in patients with peripheral artery disease who underwent endovascular therapy. AB - BACKGROUND: Kidney dysfunction is associated with adverse outcome in patients with peripheral artery disease (PAD). Renal tubulointerstitial damage (RTD) is another type of kidney dysfunction from glomerular damage. RTD is reported to be a risk for future cardiac event in patients with heart disease. However, it remains to be determined whether RTD is predictive of poor clinical outcome in patients with PAD. METHODS AND RESULTS: RTD markers (urinary N-acetyl-beta-D glucosamidase; NAG and urinary beta-2 microglobulin to creatinine ratio) and Glomerular damage markers (cystatin C-based estimated glomerular filtration rate, proteinuria, and microalbuminuria) were measured in 265 consecutive PAD patients who underwent endovascular therapy. Patients were prospectively followed for a median length of 804days, with end points of major adverse cardiovascular and cerebrovascular events (MACCE). Overall, 73% of patients exhibited excess urinary NAG excretion, and values were higher in patients with critical limb ischemia. A multivariate Cox proportional hazard analysis revealed that NAG was an independent predictor of MACCE. When patients were divided according to NAG level, Kaplan-Meier analysis demonstrated that the third tertile was associated with the greatest risk for MACCE. The C index in NAG was the greatest among kidney dysfunction markers. Moreover, the net reclassification index was improved by the addition of NAG to basic predictors including glomerular damage markers. CONCLUSION: RTD is common and associated with disease severity and clinical outcome in patients with PAD, indicating that it could be the additional clinical information to glomerular damage in patients with PAD. PMID- 27390959 TI - Dyssynchrony and electromechanical delay are associated with focal fibrosis in the systemic right ventricle - Insights from echocardiography. AB - BACKGROUND: Systemic right ventricular (RV) dysfunction and sudden cardiac death remain problematic late after Mustard operation for transposition of the great arteries. The exact mechanism for that relationship is likely to be multifactorial including myocardial fibrosis. Doppler echocardiography gives further insights into the role of fibrosis shown by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in late morbidity. METHODS AND RESULTS: Twenty-two consecutive patients, mean age 28+/-8years, were studied with 2D echocardiography, and also assessed by LGE CMR. The presence of LGE in 13/22 patients (59%) was related to delayed septal shortening and lengthening (P=0.002 &P=0.049), prolonged systemic RV isovolumic contraction time (P=0.024) and reduced systemic RV free wall and septal excursion (P=0.027 &P=0.005). The systemic RV total isovolumic time was prolonged but not related to extent of LGE. LGE extent was related to markers of electromechanical delay and dyssynchrony (delayed onset of RV free wall shortening and lengthening; r=0.73 &P=0.004 and r=0.62 &P=0.041, respectively, and QRS duration r=0.68, P<0.01) and was inversely related to systolic RV free wall shortening velocity (r=-0.59 &P=0.042). The presence of LGE was also related to lower exercise capacity, >=mild tricuspid regurgitation and more arrhythmia (P=0.008, P=0.014 and P=0.040). RV free wall excursion and systolic tissue Doppler velocity were related to CMR derived RV ejection fraction (r=0.51, P=0.015, and r=0.77, P=<0.001, respectively). CONCLUSION: Post Mustard repair, myocardial fibrosis is related to dyssynchrony, RV long axis dysfunction and tricuspid regurgitation. Echocardiographic measurements of systemic RV function can be confidently used in serial follow-up following Mustard operation. PMID- 27390960 TI - Electrocardiographic measurement of infarct size compared to cardiac MRI in reperfused first time ST-segment elevation myocardial infarction. AB - BACKGROUND: Myocardial infarct size (IS) following ST-segment elevation myocardial infarction (STEMI) is an important prognostic factor. We assessed the Selvester 32-point QRS score from the 12-lead ECG for measurement of IS in STEMI patients receiving reperfusion therapy compared to cardiac magnetic resonance imaging (CMRI). Furthermore we sought to explore the impact of microvascular obstruction (MVO) on the scoring system, and determine factors contributing to discrepancies between CMRI IS and Selvester score. METHODS: We examined 70 patients (55 men, 15 women), mean age 57+/-10years with a first time STEMI (46 anterior, 24 non-anterior). QRS scores were calculated early and at follow-up (mean 2+/-1 and 59+/-14days post-STEMI). Myocardial core scar size (5SD) was measured at 5.3+/-3.3 and 57.8+/-13.5days post-infarction by CMRI. MVO was determined on initial MRI. Logistic regression analysis was performed to determine factors contributing to discordant scores, defined as a difference between CMRI and Selvester IS of >6% myocardium. RESULTS: QRS scoring of anterior infarcts correlated with CMRI IS both early (r=0.734, p<0.0001) and at follow-up (r=0.716, p<0.0001); however no correlation was seen among non-anterior infarcts. QRS scoring overestimated IS at all time points. There was better agreement between ECG and CMRI measured IS in patients without MVO at both time points. Anterior infarction was inversely predictive of discordant IS estimation acutely, and larger Selvester scores were predictive of inaccurate scoring at both time periods. CONCLUSIONS: Selvester QRS score correlates well with CMRI IS for anterior infarcts. MVO did not independently affect the score. PMID- 27390961 TI - Durability of cryothermal pulmonary vein isolation - Creating contiguous lesions is necessary for persistent isolation. AB - BACKGROUND: Electrical reconnections after pulmonary vein isolation (PVI) are common in catheter ablation. This study aimed to evaluate the impact of the ablation method on the durability of cryothermal PVI. METHODS: One hundred thirty two consecutive paroxysmal atrial fibrillation patients undergoing cryothermal PVI were enrolled. PVI was performed with one 28-mm second-generation balloon using 3-minute freeze techniques, and touch-up lesions were created by focal cryothermal applications. RESULTS: Out of 520 PVs, 503 (96.7%) were isolated using exclusively cryoballoons, and 17 required additional focal ablation. Adenosine testing was performed in 111 patients for 439 PVs including 427 isolated with cryoballoons and 12 isolated by focal ablation. The incidence of dormant conduction was significantly higher in PVs isolated by focal ablation than by cryoballoons (4/12 vs. 3/427 PVs, p<0.0001). All latent conduction was successfully eliminated by additional cryoapplications. In 36 patients, 142 PVs were re-evaluated during repeat procedures a median of 6 [4.3-9.0] months after the initial procedure. Late reconnections were detected in 32 (22.5%) PVs. The incidence of late reconnections was significantly higher in PVs isolated by focal ablation than by cryoballoons (5/6 vs. 27/136 PVs, p=0.0003). Among the PVs requiring touch-up ablation, both the acute dormant conduction and late reconnection sites were identical to sites requiring touch-up ablation. CONCLUSIONS: The incidence of both acute latent and late PV reconnections was significantly higher when PVI was achieved by focal cryoablation than by cryoballoon ablation despite using the same energy source. These data suggest that creating contiguous lesions is essential for achieving a durable PVI. PMID- 27390962 TI - A plausible causal link between antiretroviral therapy and increased blood pressure in a sub-Saharan African setting: A propensity score-matched analysis. AB - BACKGROUND: The transition from association to causation could represent a fundamental step for taking preventive action against hypertension and its complications, especially among HIV-infected persons on antiretroviral therapy in sub-Saharan African countries. METHODS: 406 consecutive HIV-infected adults attending a tertiary HIV clinic in semi-urban Nigeria were prospectively recruited between August and November 2014. These participants were stratified by antiretroviral treatment status. A propensity score matching model was fitted to examine the causal average treatment effects on the treated (ATT) of antiretroviral therapy on blood pressure. Propensity score matching entailed using nearest neighbour matching with a calliper width of 0.2 to achieve similarity in the baseline characteristics between participants naive and exposed to antiretroviral therapy. RESULTS: Matching HIV-infected patients naive and exposed to antiretroviral therapy on the propensity score yielded a total of 303 participants - 229 antiretroviral-exposed and 74 antiretroviral-naive - matched without any residual differences in the baseline characteristics between both groups of patients. In this propensity score-matched sample, the estimated ATT for the effects of antiretroviral therapy on systolic (7.85mmHg, 95% CI 3.72 to 15.68) and diastolic blood pressure (7.45mmHg, 95% CI 4.99 to 13.61) were statistically significant (P<0.001 for each). CONCLUSIONS: There is a high probability that the epidemiological association between antiretroviral therapy and increased blood pressure be causal in nature among people living with HIV in sub-Saharan African settings. HIV-infected patients commencing antiretroviral treatment in these settings may require regular hypertension screening and other cardiovascular risk assessments. PMID- 27390963 TI - Telerehabilitation in heart failure patients: The evidence and the pitfalls. AB - Accessibility to the available traditional forms of cardiac rehabilitation programs in heart failure patients is not adequate and adherence to the programs remains unsatisfactory. The home-based telerehabilitation model has been proposed as a promising new option to improve this situation. This paper's aims are to discuss the tools available for telemonitoring, and describing their characteristics, applicability, and effectiveness in providing optimal long term management for heart failure patients who are unable to attend traditional cardiac rehabilitation programs. The critical issues of psychological support and adherence to the telerehabilitation programs are outlined. The advantages and limitations of this long term management modality are presented and compared with alternatives. Finally, the importance of further research, multicenter studies of telerehabilitation for heart failure patients and the technological development needs are outlined, in particular interactive remotely controlled intelligent telemedicine systems with increased inter-device compatibility. PMID- 27390964 TI - The ventricular late potentials in children with vasodepressor response of vasovagal syncope. AB - OBJECTIVES: To discuss ventricular late potentials (VLPs) in children with vasodepressor response of vasovagal syncope (VVS-V). METHODS: 184 children diagnosed as VVS-V by head-up tilt test (HUTT) were enrolled as VVS-V group, 105 age and gender matched healthy individuals without syncope were used as control group, then signal-averaged electrocardiogram was measured. RESULTS: HR was decreased [(83.98+/-12.27) vs (87.28+/-13.75)bpm, P<0.05] in VVS-V group compared with control group. The prevalence of positive VLPs was not significantly different between the two groups. However the absolute values of TQRS [(84.89+/ 12.05) vs (81.21+/-8.23)ms, P<0.01], RMS40 [(28.73+/-7.23) vs (26.89+/-7.36)MUV, P<0.05] and LAS40 [(62.43+/-19.17) vs (56.79+/-1.83)ms, P<0.05] were significantly prolonged in VVS-V group compared with control group, and more patients in VVS-V group had abnormal prolonged LAS40 (94.57% vs 83.80%, P<0.01). CONCLUSIONS: The prevalence of positive VLPs was not significantly different, TQRS, RMS40, LAS40 were longer in children with VVS-V in comparison with healthy individuals, and the abnormal LAS40 occurred in a higher proportion of VVS-V group. PMID- 27390965 TI - Dabigatran in clinical practice: Contemporary overview of the evidence. AB - Oral anticoagulation is the cornerstone of stroke prevention in non-valvular atrial fibrillation (AF) and management of venous thromboembolism (VTE), resulting in a reduction in thrombotic complications and mortality. Benefit of vitamin K antagonists (VKAs) in such patients has been unambiguously confirmed, but VKA use is complicated by need for regular monitoring of the international normalized ratio and multiple drug and food interactions. Dabigatran is an oral direct thrombin inhibitor that can be used with fixed doses, without the need for routine anticoagulation laboratory monitoring and the advantage of few drug or diet interactions. Dabigatran is effective for stroke and systemic thromboembolism in AF and for the prophylaxis and treatment of VTE. The drug has a good safety profile and consistently shows a reduction in intracranial hemorrhage risk compared to warfarin. A specific reversal agent for dabigatran has been approved by FDA and EU. This review provides a summary of publications assessing clinical utility of dabigatran for different indications. PMID- 27390967 TI - Effect of vagotomy on the activity of cardiac autonomic ganglia: Insight from left atrial high density frequency mapping. AB - BACKGROUND: Both extrinsic and intrinsic cardiac autonomic nervous systems are important for initiation and maintenance of atrial fibrillation (AF). We aimed to evaluate the effect of vagotomy on the activity of cardiac autonomic ganglionated plexi (GP) and the change of dominant frequency (DF) distribution in the left atrium (LA) during AF. METHODS: A mid-sternal thoracotomy was performed in 6 dogs. High frequency stimulation was applied to locate the GPs. There were four major LA GPs, which were located near the pulmonary vein ostia, and a superior vena cava-aorta (SVC-Ao) GP that was located near the superior vena cava-right atrial junction. Acetylcholine patch was applied on GPs to induce intrinsic vagal response. Vagal denervation was performed thereafter. An Ensite Array was deployed in the LA to record atrial signals before and after vagotomy during induced AF. RESULTS: The LA mean DF values (8.2+/-0.1 vs. 7.6+/-0.1Hz, p=0.002) were higher during GP activation before than after vagotomy. The maximal DF distribution was located at the primary GPs and the nearby secondary GPs during LA GPs activation and at the LA septum and right superior pulmonary vein during SVC-Ao GP activation before vagotomy. After vagotomy, the maximal DF distribution shifted to non-GP LA sites during activation of the GPs. CONCLUSIONS: The findings suggest the important role of the extrinsic neural input in the activation and interaction of the intrinsic cardiac autonomic activity during cholinergic AF, whereas the non-GP LA sites were responsible for the AF induced without the physiological extrinsic neural input. PMID- 27390966 TI - Drug-induced aortic valve stenosis: An under recognized entity. AB - BACKGROUND: We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. METHODS: Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. RESULTS: Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was >= mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. CONCLUSION: The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS. PMID- 27390968 TI - Medical treatment of stable angina: A tailored therapeutic approach. PMID- 27390969 TI - Moderate hypothermia increased the incidence of delayed paralysis through activation of the spinal microglia in an aortic cross-clamping rat model. AB - BACKGROUND: Hypothermia reduces immediate paralysis during surgical repair of aortic aneurysms. However, it is unknown what the impact of hypothermia is on delayed paralysis, a serious complication of this type of surgery. METHODS: Sprague-Dawley rats were subjected to occlusion of the descending aorta at different duration under normothermia (38.0+/-0.5) or hypothermia (33.0+/-0.5 degrees ). Neurologic function was assessed. Motor neuron number, glial activation, and cytokine expression in the spinal cord were examined. Minocycline was administered perioperatively by intraperitoneal injection in the rats subjected to the aorta occlusion. RESULTS: In contrast to normothermia conditions at which immediate paralysis occurred when the duration of aorta occlusion exceeded 11.5min, hypothermia did not induce immediate paralysis if the duration of aorta occlusion was less than 41min. However, delayed paralysis was developed when the duration of aorta occlusion exceeded 18min, and reached peak level when the duration of aorta occlusion was 40min at hypothermia condition. The number of motoneurons was significantly decreased (P<0.05) at 30h postoperation. In addition, microglia was activated, and interleukin-1beta and interleukin-6 levels were upregulated, both of which were co-localized in microglia at 24h postoperation in the hypothermia group. Minocycline treatment attenuated the incidence and degree of paralysis but did not decrease the mortality. CONCLUSIONS: Hypothermia, a neuroprotective strategy in cardiothoracic surgery, increased the incidence of delayed paralysis through activation of spinal microglia and cytokines. Blocking the activated microglia may be a potential intervention to prevent the incidence of delayed paralysis. PMID- 27390970 TI - Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension. AB - OBJECTIVE: The effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) on dementia risk in patients with type 2 diabetes mellitus (DM) and hypertension remain unknown. We investigated the effects of ACEIs and ARBs on dementia risk in patients with type 2 DM and hypertension. METHODS: We conducted a cohort study by using the Taiwan National Health Insurance Research Database. We included 2377 patients receiving ACEIs and 1780 patients receiving ARBs in the ACEI and ARB cohorts, respectively. We included a comparable number of patients not receiving ACEIs and ARBs as controls in the non-ACEI and non-ARB cohorts through propensity score matching. The effect of ACEIs and ARBs on dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. RESULTS: During the 12-year follow-up period, compared with the non-ACEI cohort, all-cause dementia risk decreased by 26% in the ACEI cohort [hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.56-0.96]. The all-cause dementia risk was nearly 40% lower in the ARB cohort than in the non-ARB cohort (HR=0.60, 95% CI=0.37-0.97). These drugs prevented the occurrence of vascular dementia (VD), however, this effect was nonsignificant for Alzheimer's dementia (AD). Treatment duration- and dosage-related protection effects on dementia occurrence were observed. CONCLUSIONS: ACEIs and ARBs may effectively prevent all-cause dementia, particularly VD, in patients with type 2 DM and hypertension. Moreover, compared with ACEIs, ARBs appear to be more advantageous in dementia prevention. PMID- 27390971 TI - High pulse pressure is related to risk of type 2 diabetes mellitus in Chinese middle-aged females. AB - BACKGROUND: To examine the association of risk of incident type 2 diabetes mellitus (T2DM) with high pulse pressure (PP) by sex. METHODS: We performed a prospective cohort study of 12,272 eligible participants (4664 males and 7608 females) without diabetes at baseline. Participants were classified as having normal PP (20-60mmHg) and high PP (>60mmHg) at baseline. The analysis was further stratified by sex, quartiles of age and high PP categories. RESULTS: During 6years of follow-up, T2DM developed in 775 participants and the incidence was 10.57/1000person-years. With PP 70 to 76mmHg, the multivariable adjusted hazard ratio (HR) (95% confidence interval) for incident T2DM in females was 1.722 (1.093-2.714) after adjustment for baseline age, smoking, alcohol intake, physical activity level and family history of T2DM, and 1.634 (1.037-2.575) after adjustment for the above factors and body mass index, waist circumference, blood lipid levels and fasting plasma glucose (FPG) category. After stratification by quartiles of age, for females aged 52 to 59, the multivariable adjusted HRs (95% CI) for high PP as compared to normal PP were 2.263 (1.517-3.377) and 2.140 (1.426-3.210) in different models. During follow-up, levels of FPG, fasting plasma insulin and homeostatic model assessment of insulin resistance index (HOMA IR) were higher in females with higher than normal PP group, but beta-cell function was impaired in the high PP group (P<0.05). CONCLUSION: High PP may be related to incident T2DM among female in China, especially women 52 to 59years old. PMID- 27390972 TI - Sapien 3 versus Sapien XT prosthetic valves in transcatheter aortic valve implantation: A meta-analysis. AB - OBJECTIVES: The S3 prosthetic valve was introduced to overcome several issues with its predecessor, the SXT, in transcatheter aortic valve implantation (TAVI), however, the clinical outcomes of this new model are not clearly defined. We performed a meta-analysis to compare the outcomes in Sapien 3 (S3) and Sapien XT (SXT) recipients. METHODS: A literature search through PUBMED and EMBASE was conducted. Articles that included at least one of the clinical outcomes of interest were included in the meta-analysis: moderate to severe paravalvular regurgitation (PVR), permanent pacemaker implantation (PPI), major vascular complications (MVC), cerebrovascular events (stroke and transient ischemic attack) (CVE), failure rate of device implantation, life-threatening, disabling or major bleeding, need for post-dilation and early all-cause-mortality. RESULTS: A total of 9 observational cohort studies were included. S3 was implanted in 945 and SXT in 1553 patients. S3 was associated with a lower incidence of moderate to severe PVR (1.6% vs 6.9%, p<0.0001), lower MVC (5.1% vs 8.9%, p=0.01) and less serious bleeding (8.1% vs 15.2%, p=0.003) compared to the SXT. Device deployment failure rate was lower in the S3 (1.2% vs 5.9%, p=0.004) and the S3 required less post-dilation (16.9% vs 26.9%, p=0.05). Rates of CVE, perioperative mortality and PPI were similar between the two valves. CONCLUSIONS: Implantation of the S3 prosthetic valve results in lower rates of moderate to severe PVR, MVC, post dilation and serious bleeding however it does not improve on the SXT in terms of CVE, PPI and early mortality. PMID- 27390973 TI - Emergency department triage of acute heart failure triggered by pneumonia; when an intensive care unit is needed? AB - Community acquired pneumonia (CAP) is a frequent triggering factor for decompensation of a chronic cardiac dysfunction, leading to acute heart failure (AHF). Patients with AHF exacerbated by CAP, are often admitted through the emergency department for ICU hospitalization, even though more than half the cases do not warrant any intensive care treatment. Emergency department physicians are forced to make disposition decisions based on subjective criteria, due to lack of evidence-based risk scores for AHF combined with CAP. Currently, the available risk models refer distinctly to either AHF or CAP patients. Extrapolation of data by arbitrarily combining these models, is not validated and can be treacherous. Examples of attempts to apply acuity scales provenient from different disciplines and the resulting discrepancies, are given in this review. There is a need for severity classification tools especially elaborated for use in the emergency department, applicable to patients with mixed AHF and CAP, in order to rationalize the ICU dispositions. This is bound to facilitate the efforts to save both lives and resources. PMID- 27390974 TI - Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure. AB - BACKGROUND: It has been reported that skeletal muscle mass and strength are decreased in patients with heart failure (HF), and HF is associated with both reduced exercise capacity and adverse clinical outcomes. Myostatin has been known as a negative regulator of muscle growth, follistatin as the myostatin antagonist, maintaining tissue homeostasis. We thus determined serum myostatin levels in HF patients and whether they are associated with skeletal muscle wasting. METHODS AND RESULTS: Forty one consecutive HF patients (58+/-15years old, New York Heart Association class I-III) and 30 age-matched healthy subjects as controls (53+/-8years old) were studied. Serum myostatin levels were significantly lower in HF patients than controls (18.7+/-7.4 vs. 23.6+/-5.2ng/mL, P<0.001). Circumference of the thickest part of the right thigh was significantly small (468+/-72 vs. 559+/-37mm, P=0.001) and lower extremity muscular strength was lower in patients with HF (129+/-55 vs. 219+/-52N*m, P<0.001). Fourteen HF patients (34%) had muscle wasting. By univariate analysis, higher age, higher serum follistatin, and lower serum myostatin were significantly associated with the presence of muscle wasting. By multivariate analysis, serum myostatin levels were independently associated with muscle wasting (OR=0.77, 95% CI [0.58, 0.93], P=0.02). CONCLUSION: Serum myostatin levels were significantly decreased in HF patients and associated with lower extremity muscle wasting, suggesting that myostatin may be an important factor for maintaining skeletal muscle mass and strength in HF. PMID- 27390976 TI - Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes. AB - BACKGROUND: Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin. METHODS: We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation. RESULTS: Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively). CONCLUSIONS: The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725. PMID- 27390975 TI - Safety and effectiveness of the new P2Y12r inhibitor agents vs clopidogrel in ACS patients according to the geographic area: East Asia vs Europe. PMID- 27390977 TI - Vitamin D levels and cardiometabolic risk factors in Portuguese adolescents. AB - BACKGROUND: Growing evidence suggests a possible association between low vitamin D levels and increased cardiovascular risk. However, research regarding the period of adolescence is scarce. We aimed to evaluate the association of vitamin D, intake and serum 25(OH)D levels, with cardiometabolic risk factors in 13-year old adolescents. METHODS: We conducted a cross-sectional analysis of 1033 adolescents evaluated at 13years old as part of the population-based cohort EPITeen. Vitamin D intake was assessed by a food frequency questionnaire. Serum 25(OH)D levels were assessed for a subsample of 514 participants. Metabolic syndrome (MetS) features were defined according to the National Cholesterol Education Program Adult Treatment Panel III definition modified for age. Logistic regression was fitted to estimate the association between vitamin D status and cardiometabolic risk factors, adjusting for sex, parental education, BMI, physical activity and season. RESULTS: Mean (SD) vitamin D levels, 4.61 (2.50)MUg for intake and 16.52 (5.72)ng/mL for serum, were below the recommendations. The prevalence of MetS was 13.2%. Total cholesterol and LDL levels significantly decreased with 25(OH)D serum increase. After adjustment, no association was found between vitamin D levels and MetS. Regarding MetS features, an increased odds of high BMI was observed for those with a lower intake (OR 1.87 95% CI 1.04-3.35). CONCLUSIONS: Although a significant increase in total and LDL cholesterol was observed for lower 25(OH)D levels, and an increased odds of high BMI was observed for those with a lower vitamin D intake, no significant association was observed between vitamin D levels and metabolic syndrome. PMID- 27390978 TI - Effects of biological age on the associations of blood pressure with cardiovascular and non-cardiovascular mortality in old age: A population-based study. AB - BACKGROUND/OBJECTIVES: Whether chronological or biological age may play a role in the association between blood pressure and cause-specific mortality in old age is unclear. We seek to investigate the associations of blood pressure with all cause, cardiovascular, and non-cardiovascular mortality among older people and to explore whether chronological age and biological age may modify the associations. METHODS: This cohort study included 3014 participants (age>=60years, 64.0% women) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. In 2001-2004, data were collected through interviews, clinical examinations, and inpatient register. Survival status and causes of deaths till 2011 for all participants were ascertained from Swedish death register. Data were analyzed with Cox proportional hazard models for all-cause mortality, and Fine-Gray competing risks models for cause-specific mortality. RESULTS: During 23,788 person-years of follow-up (median per person, 8.4years), 933 (31.0%) participants died. Systolic blood pressure<130mmHg (vs. 130-139mmHg) was significantly associated with decreased all-cause mortality (hazard ratio=0.59, 95% confidence interval=0.40-0.87) and non-cardiovascular mortality (0.59, 0.36-0.98) in biologically young people (persons with neither cognitive impairment nor mobility limitation), but with increased all-cause mortality (1.63, 1.22-2.16) and non cardiovascular mortality (2.18, 1.27-3.75) in biologically old people (persons with either cognitive impairment or mobility limitation). The hazard ratio of cardiovascular mortality was increased with increasing levels of systolic blood pressure (ptrend=0.009) and diastolic blood pressure (ptrend=0.008) in biologically young people. CONCLUSIONS: Biological age plays a pivotal role in the associations of blood pressure with cardiovascular and non-cardiovascular mortality in old age. PMID- 27390979 TI - Trimetazidine attenuates the acute inflammatory response induced by Novolimus eluting bioresorbable coronary scaffold implantation. AB - BACKGROUND: This study aims to investigate the inflammatory response in Novolimus bioresorbable coronary scaffold implantation after a course treatment with trimetazidine (35mg tablet/twice daily for 4days). METHODS: This was a randomized single blind study. Forty diabetic patients with critical coronary stenosis were subjected to elective coronary scaffold implantation in Al-Najaf Center for Cardiac Surgery and Trans-Catheter Therapy, Najaf, Iraq, between January and July 2015. All patients were informed about the nature of the study and they signed the consent form before they included in the study. Patients were randomly allocated into the two study groups: Group 1 included 20 patients who did the elective coronary scaffold implementation without trimetazidine medication. Group 2 included 20 patients who did the elective coronary scaffold implementation with a course of the trimetazidine (35mg tablet/twice daily for 4days). RESULTS: There were significant reduction in the levels of the interleukin-6 and cardiac troponin-I in the trimetazidine-treated group (group 2) compared to the control group (group 1) (P<0.001), after 12h and 24h post-operative. This was associated with a significant rise in the levels of interleukin 10 in group 2 compared to group 1 (P<0.001). Pentraxin-3 was significantly reduced in group 2 but only 24h post-operative (P<0.006). CONCLUSION: Our study concluded that trimetazidine minimizes the acute inflammatory response occurred due to systemic release of inflammatory markers into blood in diabetic patients undergoing elective Novolimus bioresorbable coronary scaffold implementation. PMID- 27390980 TI - Sedentary behavior & health-related quality of life among congestive heart failure patients. AB - BACKGROUND: Previous research demonstrates that participation in light-intensity physical activity (LIPA) and moderate-to-vigorous physical activity (MVPA) are favorably associated with health-related quality of life (HRQOL). Emerging work demonstrates that sedentary behavior (SB) is detrimentally associated with various cardiometabolic biomarkers, with few studies exploring the association of SB on HRQOL, and no studies examining this among congestive heart failure patients. Therefore, the purpose of this study was to examine the potential independent associations of SB on HRQOL among congestive heart failure patients. METHODS: Data from the 2003-2006 National Health and Nutrition Examination Survey were used. Physical activity was assessed over 7days during all waking hours using the ActiGraph 7164 accelerometer. HRQOL was assessed using the Centers for Disease Control HRQOL index survey. RESULTS: 190 participants self-reported a physician-diagnosis of congestive heart failure. After adjustments, SB behavior (1-min/day increase) was associated with worse HRQOL (beta=0.004; 95% CI: 0.0004 0.007; P=0.03). When MVPA was added as a covariate to this model, SB remained significantly associated with worse HRQOL (beta=0.003; 95% CI: 0.0001-0.007; P=0.04). However, when adding LIPA to this model that also included MVPA as a covariate, SB was no longer associated with HRQOL (beta=0.0001; 95% CI: -0.003 0.004; P=0.92). CONCLUSIONS: If confirmed by prospective/experimental work, this suggests that SB may not have detrimental HRQOL effects among congestive heart failure patients. PMID- 27390981 TI - Does the time of your health screening alter your "health"? PMID- 27390982 TI - Vagal reactivation after exercise and cardiac autonomic nervous activity in adult Fontan patients without pacemakers. AB - PURPOSE: Patients with Fontan circulation have reduced heart rate variability (HRV) in supine position. However, neither cardiac autonomic nervous activity (CANA) in response to orthostatic challenge nor vagal reactivation by means of heart rate (HR) recovery after cessation of exercise have previously been investigated in Fontan patients. The aim of this study was to compare HRV in supine and standing position, as well as HR recovery between Fontan patients and healthy controls. METHODS: Eight Fontan patients (4 male/4 female) without pacemakers and 12 healthy volunteers (5m/7f) with minimum age of 18years were recruited. HR was measured by Holter-electrocardiogram. HRV was measured in supine position and after orthostatic challenge. The power of the high frequency (HF: 0.15Hz-0.4Hz) and low frequency (LF: 0.04Hz-0.15Hz) bands was analysed by fast-Fourier transformation. HR recovery was determined at 30s and 60s after termination of a maximal exercise test. RESULTS: In both supine and standing position, total power, HF and LF power were reduced in Fontan patients compared to controls (by approximately a factor of 10) while there was no differences in LF/HF power ratio. Response to orthostatic challenge was blunted in absolute power but normal in relative power. HR recovery was not different between groups. CONCLUSION: Fontan patients have greatly reduced HRV, a blood-pressure dependent marker of CANA, but normal HR recovery, a blood pressure independent marker of vagal reactivation, suggesting that vagal activity may be normal, and only vascular capacitance reduced. PMID- 27390983 TI - Is three-dimensional speckle-tracking echocardiography able to identify different patterns of left atrial dysfunction in selected disorders?: Short summary of the MAGYAR-Path Study. PMID- 27390984 TI - Heart failure in women and men during acute coronary syndrome and long-term cardiovascular mortality (the ABC-3* Study on Heart Disease) (*Adria, Bassano, Conegliano, and Padova Hospitals). AB - AIMS: We investigated the gender-based differences in the association between heart failure (HF) during acute coronary syndrome (ACS) and post-discharge, long term cardiovascular (CV) mortality. METHODS AND RESULTS: The present study included 557 patients enrolled in three intensive coronary care units and discharged alive. HF during ACS was evaluated by Killip class and left ventricular ejection fraction (LVEF). Interaction between gender and HF after 15years of follow up was studied using Cox models including a formal interaction term. Median age was 67 (interquartile range [IQR], 59-75) years, 29% were females, 37% had non-ST elevation myocardial infarction and 32% Killip class>1, and median LVEF was 53% (IQR 46-61). All but five patients were followed up to 15years, representing 5332 person-years. Of these, 40.2% died of CV-related causes. Crude CV mortality rate was higher among women (52.2%) than men (35.3%; P<0.0001). At a univariable level, a negative interaction between female gender and Killip class for CV mortality was found [hazard ratio (HR)=0.51 (0.34-0.77), P=0.002]. In five multivariable models after controlling for age, main CV risk factors, clinical features, post-discharge medical treatment, and mechanical coronary reperfusion, the interaction was significant across all models [HR=0.63 (0.42-0.95), P=0.02 in the fully adjusted model]. LVEF showed no significant hazard associated with female gender on univariable analysis [HR=1.4 (0.9-0.2.0), P=0.11] but did so in all adjusted models [HR=1.7 (1.2-2.5), P=0.005 in the fully adjusted model]. CONCLUSION: Gender is a consistent, independent effect modifier in the association between HF and long-term CV mortality after ACS. PMID- 27390985 TI - Economic burden of venous thromboembolism: Are novel oral anticaoagulants the possible solution? PMID- 27390986 TI - Effect of dance therapy on blood pressure and exercise capacity of individuals with hypertension: A systematic review and meta-analysis. AB - BACKGROUND: Dance therapy is a less conventional modality of physical activity in cardiovascular rehabilitation. We performed a systematic review and meta-analysis to investigate the effects of dance therapy in hypertensive patients. METHODS: Pubmed, Scopus, LILACS, IBECS, MEDLINE and SciELO via Virtual Health Library (Bireme) (from the earliest data available to February 2016) for controlled trials that investigated the effects of dance therapy on exercise capacity, systolic (SBP) and diastolic (DBP) blood pressure in hypertensive patients. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I(2) test. RESULTS: Four studies met the eligibility criteria. Dance therapy resulted in a significant reduction in systolic blood pressure (WMD -12.01mmHg; 95% CI: -16.08, -7.94mmHg; P<0.0001) when compared with control subjects. Significant reduction in diastolic blood pressure were also found (WMD -3.38mmHg; 95% CI: -4.81, -1.94mmHg; P<0.0001), compared with control group. Exercise capacity showed a significant improvement (WMD 1.31; 95% CI: 0.16, 2.47; P<0.03). A moderate to high heterogeneity was observed in our analysis: I(2)=92% to SBP, I(2)=55% to DBP, and I(2)=82% to exercise capacity. CONCLUSIONS: Our meta-analysis showed a positive effect of dance therapy on exercise capacity and reduction of SBP and DBP in individuals with hypertension. However, the moderate to high heterogeneity found in our analysis limits a pragmatic recommendation of dance therapy in individuals with hypertension. PMID- 27390987 TI - Importance of papillary muscle infarction detected by cardiac magnetic resonance imaging in predicting cardiovascular events. AB - BACKGROUND: Recent studies suggest that papillary muscle infarction (PMI) following recent myocardial infarction (MI) correlates with adverse cardiovascular outcomes. The purpose of this study is to determine the prevalence and prognostic significance of PMI by cardiac magnetic resonance (CMR) in a large cohort of patients. METHODS: Retrospective study of patients who underwent CMR between January 2007 and December 2009 were evaluated for the presence of PMI in one or both of the left ventricle papillary muscles. The primary outcome was a time to a combined endpoint of all-cause mortality and worsening heart failure. Secondary outcomes were time to individual components of the combined outcome. RESULTS: 419 patients were included in our analysis, 232 patients (55%) had ischemic cardiomyopathy. Patients were followed at six-month intervals for a median follow-up time of 3.7 (interquartile range (IQR): 1.6; 6.3) years after initial imaging. During this period 196 patients (46.8%) had a primary outcome and 92 patients (22%) died. PM infarct was identified in 204 (48.7%) patients with twice as many posteromedial (PRM) (27%) than anterolateral (ARL) lesions (11%) and a similar number with infarct in both (11%). There was no association between studied outcomes and the presence of PMI in either PRM or ARL PM. The presence of infarct in both PM was a predictor of both the primary outcome (HR 1.69, CI[1.01-2.86], p<0.049.) and mortality (HR 1.69, CI[1.01-4.2], p<0.046). CONCLUSION: The presence of infarct in either papillary muscle was not associated with outcomes. However, infarct involving both papillary muscles was associated with worse outcomes. PMID- 27390988 TI - When is the right time for Fontan conversion? The role of cardiopulmonary exercise test. AB - BACKGROUND: To determine if Fontan conversion (FC) resulted in improvement in exercise capacity (EC), and to determine the role of cardiopulmonary exercise test (CPET) in risk stratification of patients undergoing FC. METHODS: A retrospective review of patients who underwent CPET prior to FC at Mayo Clinic from 1994 to 2014. The patients who also underwent post-operative CPET were selected for the analysis of improvement in EC defined as 10% increase in baseline peak oxygen consumption (VO2). RESULTS: 75 patients CPET prior to FC; mean age 24+/-6years; 44 males (59%); and 51 (68%) were in NYHA III/IV prior to FC. Pre-operative peak VO2 was 15.5+/-3.4ml/kg/min. A comparison of pre- and post FC CPET data was performed using 42 patients (56%) that underwent CPET after FC. Improvement in EC occurred in 18 of 42 patients (43%). Baseline peak VO2 >14ml/kg/min was associated with improved EC (hazard ratio [HR] 1.85; P=.02). Improvement in New York Heart Association (NYHA) class occurred in 12 (67%) patients with improved EC vs 2 (8%) without improved EC. Improvement in NYHA class was more likely to occur in patients with improved EC compared to those without improvement EC (odds ratio 4.11, P=.01). There were 10 (13%) perioperative deaths, and baseline peak VO2 <=14ml/kg/min was predictive of perioperative mortality (HR 3.74; P<.001). CONCLUSIONS: Baseline peak VO2 was predictive of perioperative survival, and improvement in EC. Performance on CPET in failing Fontan patients might be a useful clinical parameter in determining appropriate timing of FC. PMID- 27390989 TI - Thrombophilias and new oral anticoagulants, a safe alternative to warfarin? PMID- 27390990 TI - Molecular mechanism of ischemia - Reperfusion injury after myocardial infarction and its possible targeted treatment. PMID- 27390991 TI - Saxagliptin and risk of heart failure hospitalization: Concern or miscalculation? PMID- 27390992 TI - Potential benefits of exercise training in rheumatic severe mitral valve stenosis in a heavy trainer. PMID- 27390993 TI - First-in-man treatment of severe blood pressure variability with baroreflex activation therapy. PMID- 27390995 TI - Treatment of bifurcation lesions with drug-coated balloons: A review of currently available scientific data. AB - Bifurcation lesion management still represents a challenge for interventional cardiologists and currently there is a number of different approaches/techniques involving coronary stents. The use of a drug-coated balloon for native coronary vessel management is emerging as an alternative treatment, although in selected patient populations only. In particular, this technology has been tested for the treatment of bifurcations, both for the main vessel and the side branches. Several studies have evaluated this treatment as an alternative or as a therapeutic option complementary to stents, with conflicting and debatable results. However, the perspective of leaving lower metallic burden in this type of lesions is highly appealing and should be deeply investigated. We review here the currently available scientific data and future perspectives on drug-coated balloon use for bifurcation lesions. PMID- 27390994 TI - Post-operative atrial fibrillation is associated with a pre-existing structural and electrical substrate in human right atrial myocardium. AB - BACKGROUND: Post-operative atrial fibrillation (POAF) is a major health economic burden. However, the precise mechanisms in POAF remain unclear. In other forms of AF, sites of high dominant frequency (DF) in sinus rhythm (SR) may harbour 'AF nests'. We studied AF inducibility in relation to substrate changes using epicardial electrograms and cardiomyocyte calcium handling in the atria of AF naive patients. METHOD: Bipolar electrograms were recorded from the lateral right atrial (RA) wall in 34 patients undergoing coronary surgery using a high-density array in sinus rhythm (NSR). RA burst pacing at 200/500/1000ms cycle lengths (CL) was performed, recording episodes of AF>30s. Co-localised RA tissue was snap frozen for RNA and protein extraction. RESULTS: Electrograms prolonged during AF (76.64+/-29.35ms) vs. NSR/pacing (p<0.001). Compared to NSR, electrogram amplitude was reduced during AF and during pacing at 200ms CL (p<0.001). Electrogram DF was significantly lower in AF (75.87+/-23.63Hz) vs. NSR (89.33+/ 25.99Hz) (p<0.05), and NSR DF higher in AF inducible patients at the site of AF initiation (p<0.05). Structurally, POAF atrial myocardium demonstrated reduced sarcolipin gene (p=0.0080) and protein (p=0.0242) expression vs. NSR. Phospholamban gene and protein expression was unchanged. SERCA2a protein expression remained unchanged, but MYH6 (p=0.0297) and SERCA2A (p=0.0343) gene expression was reduced in POAF. CONCLUSIONS: Human atrial electrograms prolong and reduce in amplitude in induced peri-operative AF vs. NSR or pacing. In those sustaining AF, high DF sites in NSR may indicate 'AF nests'. This electrical remodelling is accompanied by structural remodelling with altered expression of cardiomyocyte calcium handling detectable before POAF. These novel upstream substrate changes offer a novel mechanism and manifestation of human POAF. PMID- 27390996 TI - Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis. AB - BACKGROUND: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4 Is and SGLT2-Is on CV events and mortality by meta-analysis. METHODS: Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included. RESULTS: 157 randomized trials (114 on DPP4-Is and 43 on SGLT2-Is) enrolling 140,470 patients (107,100 in DPP4-I and 33,370 in SGLT2-I studies) were included in the analysis. Compared to control, treatment with DPP4-Is did not affect all-cause (RR: 1.010; 95% CI: 0.935-1.091) and CV (RR: 0.975; CI: 0.887-1.073) mortality as well as risk of MI (RR: 0.915; CI: 0.835-1.002), stroke (RR: 0.933; CI: 0.820-1.062) and HF (RR: 1.083; CI: 0.973-1.205). Treatment with SGLT2-Is significantly reduced the risk of all-cause death by 28% (RR: 0.718; CI: 0.613-0.840), CV death by 33% (RR: 0.668; CI: 0.544-0.821), MI by 20% (RR: 0.803; CI: 0.668-0.965) and HF by 35% (RR: 0.652; CI: 0.517-0.823) without effect on stroke (RR: 1.158; CI: 0.912 1.469). CONCLUSIONS: DPP4-Is show a safe CV profile as they do not affect mortality and CV events, including HF, in patients with type 2 DM. SGLT2-Is are associated with improved CV outcome and survival in DM patients. PMID- 27390997 TI - Rivaroxaban, a factor Xa inhibitor, induces the secondary prevention of cardiovascular events after myocardial ischemia reperfusion injury in mice. AB - OBJECTIVES: Rivaroxaban has been shown to reduce overall death from cardiovascular causes in patients with recent acute coronary syndrome. Therefore, we evaluated the secondary prevention of cardiovascular events after myocardial ischemia reperfusion injury and its mechanisms in mice. METHODS: After myocardial reperfusion injury, C57BL/6J mice were randomized to receive either no treatment or treatment for 14days with low and high doses of rivaroxaban. After 7days, mice were administered tissue factor as a secondary event. RESULTS: Based on a Kaplan Meier curve analysis, the high-dose rivaroxaban group showed a significantly higher % survival than the no-treatment group from day 7 (after the administration of tissue factor) to day 14 (at the end of the experimental period). Left ventricular (LV) ejection fraction in both the low- and high-dose rivaroxaban groups improved compared to that in the no-treatment group. Moreover, mRNA levels of interleukin-6 and collagens 1alpha2 and 3alpha1 in the LV in the high-dose group were significantly suppressed compared to those in the no treatment group. CONCLUSIONS: Rivaroxaban improved the survival rate, probably by improving cardiac function through the reduction of inflammatory and fibrotic factors in the LV. This effect may be due to the pleiotropic effects of rivaroxaban beyond its main effect as an anti-coagulant. PMID- 27390998 TI - Long-term outcome and predictors of outcome in patients with non-ischemic dilated cardiomyopathy. AB - BACKGROUND: The study objectives were to identify predictors of outcome and to assess the long-term outcome in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: From 2004 to 2008, 206 consecutive patients (age 52.1+/-12.6years) with non-ischemic DCM were prospectively enrolled in the study and followed up for a mean of 55.6+/-18.4months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of all-cause mortality or heart transplantation. During the follow-up period 47 patients died (22.8%) and 5 patients (2.4%) underwent heart transplantation for end-stage heart failure. For the primary end point, a systolic LVEF <35% (hazard ratio 2.56; 95% confidence interval 1.21-5.45; p=0.014), a prolonged QTc interval >440ms (hazard ratio 2.56; 95% confidence interval 1.24-3.83; p=0.007) and a GFR <60ml/min/1.73m(2) (hazard ratio 2.42; 95% confidence interval 1.36-4.29; p=0.003) were identified as independent predictors, whereas the presence of an LBBB, atrial fibrillation, mild mitral regurgitation or treatment with digitalis were not significantly related to outcome. CONCLUSIONS: In patients with non-ischemic DCM, a reduced systolic LVEF <35%, a prolonged QTc interval >440ms and an abnormal renal function with a GFR <60ml/min/1.73m(2) are independent predictors of death or need for heart transplantation. PMID- 27390999 TI - Takotsubo cardiomyopathy despite severe three-vessel coronary artery disease. PMID- 27391000 TI - High sensitive Troponin T useful in clinical decision making for MitraClip implantation. PMID- 27391001 TI - What is the history of the first descriptions of the ventricular septal defects? PMID- 27391003 TI - Prognostic value of the simplified PESI score in comparison with the 2014 ESC risk model in pulmonary embolism. PMID- 27391002 TI - Association of haemodynamic changes measured by serial central venous saturation during ultrafiltration for acutely decompensated heart failure with diuretic resistance and change in renal function. AB - BACKGROUND: Patients with acute decompensated heart failure with diuretic resistance (ADHF-DR) have a poor prognosis. The aim of this study was to assess in patients with ADHF-DR, whether haemodynamic changes during ultrafiltration (UF) are associated with changes in renal function (Deltacreatinine) and whether Deltacreatinine post UF is associated with mortality. METHODS: Seventeen patients with ADHF-DR underwent 20 treatments with UF. Serial bloods (4-6 hourly) from the onset of UF treatment were measured for renal function, electrolytes and central venous saturation (CVO2). Univariate and multivariate analysis were performed to assess the relationship between changes in markers of haemodynamics [heart rate (HR), systolic blood pressure (SBP), packed cell volume (PCV) and CVO2] and Deltacreatinine. Patients were followed up and mortality recorded. Cox-regression survival analysis was performed to determine covariates associated with mortality. RESULTS: Renal function worsened after UF in 17 of the 20 UF treatments (baseline vs. post UF creatinine: 164+/-58 vs. 185+/-69MUmol/l, P<0.01). DeltaCVO2 was significantly associated with Deltacreatinine [beta coefficient of -1.3 95%CI (-1.8 to -0.7), P<0.001] and remained significantly associated with Deltacreatinine after considering changes in SBP, HR and PCV [P<0.001]. Ten (59%) patients died at 1-year and 15(88%) by 2-years. Deltacreatinine was independently associated with mortality (adjusted-hazard ratio 1.03 (1.01 to 1.07) per 1MUmol/l increase in creatinine; P=0.02). CONCLUSIONS: Haemodynamic changes during UF as measured by the surrogate of cardiac output was associated with Deltacreatinine. Worsening renal function at end of UF treatment occurred in the majority of patients and was associated with mortality. PMID- 27391004 TI - Development and validation of a risk calculator predicting exercise-induced ventricular arrhythmia in patients with cardiovascular disease. AB - BACKGROUND: Mortality due to cardiovascular disease is often associated with ventricular arrhythmias. Nowadays, patients with cardiovascular disease are more encouraged to take part in physical training programs. Nevertheless, high intensity exercise is associated to a higher risk for sudden death, even in apparently healthy people. During an exercise testing (ET), health care professionals provide patients, in a controlled scenario, an intense physiological stimulus that could precipitate cardiac arrhythmia in high risk individuals. There is still no clinical or statistical tool to predict this incidence. The aim of this study was to develop a statistical model to predict the incidence of exercise-induced potentially life-threatening ventricular arrhythmia (PLVA) during high intensity exercise. METHODS AND RESULTS: 6415 patients underwent a symptom-limited ET with a Balke ramp protocol. A multivariate logistic regression model where the primary outcome was PLVA was performed. Incidence of PLVA was 548 cases (8.5%). After a bivariate model, thirty one clinical or ergometric variables were statistically associated with PLVA and were included in the regression model. In the multivariate model, 13 of these variables were found to be statistically significant. A regression model (G) with a X(2) of 283.987 and a p<0.001, was constructed. Significant variables included: heart failure, antiarrhythmic drugs, myocardial lower-VD, age and use of digoxin, nitrates, among others. CONCLUSION: This study allows clinicians to identify patients at risk of ventricular tachycardia or couplets during exercise, and to take preventive measures or appropriate supervision. PMID- 27391005 TI - Relationship of asymmetric dimethylarginine (ADMA) with extent and functional severity of coronary atherosclerosis. AB - BACKGROUND: Elevated serum levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and atherogenesis. In patients with suspected coronary artery disease (CAD), we assessed the correlation of serum ADMA levels with extent and functional significance of coronary atherosclerosis. METHODS: We enrolled 281 patients with suspected CAD undergoing coronary angiogram. Angiographic CAD severity was evaluated by Bogaty score. In patients with angiographic evidence of at least one intermediate coronary stenosis (>=50% diameter stenosis), functional significance was assessed by fractional flow reserve (FFR). Blood samples were collected in all patients prior to coronary angiography for measurement of serum ADMA levels. RESULTS: We observed across tertiles of ADMA levels increasingly higher values of both Stenosis Score (2.25+/ 1.70 vs. 2.89+/-1.99 vs. 2.95+/-1.82, p=0.016) and Extent Index (0.52+/-0.32 vs. 0.61+/-0.39 vs. 0.72+/-0.47, p=0.003). The association between ADMA levels and Extent Index remained significant after multivariate adjustment (p=0.005). Patients with FFR <=0.80 in at least one vessel (n=113) had significantly higher ADMA levels compared with patients without functionally significant CAD (0.51 [0.43-0.64] vs. 0.46 [0.39-0.58]MUmol/L, p=0.005). Serum ADMA levels were independent predictors of abnormal FFR after adjustment for extent score (odds ratio 7.35, 95% confidence interval 1.05-56.76, p=0.046). CONCLUSIONS: Serum ADMA levels are independent predictors of coronary atherosclerosis extent and functional significance of CAD. PMID- 27391006 TI - Characteristic adaptations of the extracellular matrix in dilated cardiomyopathy. AB - Dilated cardiomyopathy (DCM) is a relatively common heart muscle disease characterized by the dilation and thinning of the left ventricle accompanied with left ventricular systolic dysfunction. Myocardial fibrosis is a major feature in DCM and therefore it is inevitable that corresponding extracellular matrix (ECM) changes are involved in DCM onset and progression. Increasing our understanding of how ECM adaptations are involved in DCM could be important for the development of future interventions. This review article discusses the molecular adaptations in ECM composition and structure that have been reported in both animal and human studies of DCM. Furthermore, we provide a transcriptome-based catalogue of ECM genes that are associated with DCM, generated by using NCBI Gene Expression Omnibus database sets for DCM. Based on this in silico analysis, many novel ECM components involved in DCM are identified and discussed in this review. With the information gathered, we propose putative pathways of ECM adaptations in onset and progression of DCM. PMID- 27391007 TI - Glu311 and Arg337 Stabilize a Closed Active-site Conformation and Provide a Critical Catalytic Base and Countercation for Green Bioluminescence in Beetle Luciferases. AB - Beetle luciferases elicit the emission of different bioluminescence colors from green to red. Whereas firefly luciferases emit yellow-green light and are pH sensitive, undergoing a typical red-shift at acidic pH and higher temperatures and in the presence of divalent heavy metals, click beetle and railroadworm luciferases emit a wider range of colors from green to red but are pH independent. Despite many decades of study, the structural determinants and mechanisms of bioluminescence colors and pH sensitivity remain enigmatic. Here, through modeling studies, site-directed mutagenesis, and spectral and kinetic studies using recombinant luciferases from the three main families of bioluminescent beetles that emit different colors of light (Macrolampis sp2 firefly, Phrixotrix hirtus railroadworm, and Pyrearinus termitilluminans click beetle), we investigated the role of E311 and R337 in bioluminescence color determination. All mutations of these residues in firefly luciferase produced red mutants, indicating that the preservation of opposite charges and the lengths of the side chains of E311 and R337 are essential for keeping a salt bridge that stabilizes a closed hydrophobic conformation favorable for green light emission. Kinetic studies indicate that residue R337 is important for binding luciferin and creating a positively charged environment around excited oxyluciferin phenolate. In Pyrearinus green-emitting luciferase, the R334A mutation causes a 27 nm red shift, whereas in Phrixotrix red-emitting luciferase, the L334R mutation causes a blue-shift that is no longer affected by guanidine. These results provide compelling evidence that the presence of arginine at position 334 is essential for blue-shifting the emission spectra of most beetle luciferases. Therefore, residues E311 and R337 play both structural and catalytic roles in bioluminescence color determination, by stabilizing a closed hydrophobic conformation favorable for green light emission, and also providing a base to accept excited oxyluciferin phenol proton, and a countercation to shield the negative charge of E311 and to stabilize excited oxyluciferin phenolate, blue shifting emission spectra in most beetle luciferases. PMID- 27391009 TI - Early mobilization versus bed rest for deep vein thrombosis. AB - Aiming to prevent thromboembolic events, bed rest was historically considered in the management of patient with deep vein thrombosis. Nevertheless early ambulation could have beneficial effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified seven systematic reviews including 10 randomized trials answering this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded early ambulation is probably effective in reducing deep vein thrombosis progression and improving limb pain, and might not increase the risk of thromboembolism. PMID- 27391008 TI - Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice. AB - Fibroblast growth factor 21 (FGF21) is an important regulator in glucose and lipid metabolism, and has been considered as a potential therapy for diabetes. The effect of FGF21 on the development and progression of diabetes-induced pathogenic changes in the aorta has not currently been addressed. To characterize these effects, type 1 diabetes was induced in both FGF21 knockout (FGF21KO) and C57BL/6 J wild type (WT) mice via multiple-dose streptozotocin injection. FGF21KO diabetic mice showed both earlier and more severe aortic remodeling indicated by aortic thickening, collagen accumulation and fibrotic mediator connective tissue growth factor expression. This was accompanied by significant aortic cell apoptosis than in WT diabetic mice. Further investigation found that FGF21 deletion exacerbated aortic inflammation and oxidative stress reflected by elevated expression of tumor necrosis factor alpha and transforming growth factor beta, and the accumulation of 3-nitrotyrocine and 4-Hydroxynonenal. FGF21 administration can reverse the pathologic changes in FGF21KO diabetic mice. These findings demonstrate that FGF21 deletion aggravates aortic remodeling and cell death probably via exacerbation of aortic inflammation and oxidative stress. This marks FGF21 as a potential therapy for the treatment of aortic damage due to diabetes. PMID- 27391010 TI - Toward a More Efficient Implementation of Antifibrillation Pacing. AB - We devise a methodology to determine an optimal pattern of inputs to synchronize firing patterns of cardiac cells which only requires the ability to measure action potential durations in individual cells. In numerical bidomain simulations, the resulting synchronizing inputs are shown to terminate spiral waves with a higher probability than comparable inputs that do not synchronize the cells as strongly. These results suggest that designing stimuli which promote synchronization in cardiac tissue could improve the success rate of defibrillation, and point towards novel strategies for optimizing antifibrillation pacing. PMID- 27391011 TI - GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis. AB - BACKGROUND: Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. RESULTS: We present an alignment free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. CONCLUSION: Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome. PMID- 27391012 TI - A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation. AB - Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)+ individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4+ T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d.) infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4+ cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4+ T cell depletion can be reversed, we employed interleukin (IL)-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8+ memory T cells, natural killer (NK) cells and double negative (DN) T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection. PMID- 27391013 TI - Coupling between Theta Oscillations and Cognitive Control Network during Cross Modal Visual and Auditory Attention: Supramodal vs Modality-Specific Mechanisms. AB - Cortical theta band oscillations (4-8 Hz) in EEG signals have been shown to be important for a variety of different cognitive control operations in visual attention paradigms. However the synchronization source of these signals as defined by fMRI BOLD activity and the extent to which theta oscillations play a role in multimodal attention remains unknown. Here we investigated the extent to which cross-modal visual and auditory attention impacts theta oscillations. Using a simultaneous EEG-fMRI paradigm, healthy human participants performed an attentional vigilance task with six cross-modal conditions using naturalistic stimuli. To assess supramodal mechanisms, modulation of theta oscillation amplitude for attention to either visual or auditory stimuli was correlated with BOLD activity by conjunction analysis. Negative correlation was localized to cortical regions associated with the default mode network and positively with ventral premotor areas. Modality-associated attention to visual stimuli was marked by a positive correlation of theta and BOLD activity in fronto-parietal area that was not observed in the auditory condition. A positive correlation of theta and BOLD activity was observed in auditory cortex, while a negative correlation of theta and BOLD activity was observed in visual cortex during auditory attention. The data support a supramodal interaction of theta activity with of DMN function, and modality-associated processes within fronto-parietal networks related to top-down theta related cognitive control in cross-modal visual attention. On the other hand, in sensory cortices there are opposing effects of theta activity during cross-modal auditory attention. PMID- 27391014 TI - Correction: Genetic Analyses of the Internal Transcribed Spacer Sequences Suggest Introgression and Duplication in the Medicinal Mushroom Agaricus subrufescens. AB - [This corrects the article DOI: 10.1371/journal.pone.0156250.]. PMID- 27391015 TI - Assessment of Retinal and Choroidal Measurements in Chinese School-Age Children with Cirrus-HD Optical Coherence Tomography. AB - PURPOSE: To evaluate retinal thickness (RT), retinal volume (RV) and choroidal thickness (ChT) in Chinese children using Cirrus-HD optical coherence tomography (OCT), and assess their associations with spherical equivalent (SE), age and gender. METHODS: This was a prospective study that recruited 193 healthy Chinese children (193 eyes) with no ophthalmic disease history between December 2012 and December 2013. RT and RV were acquired using OCT. Subfoveal ChT (SFCT) and ChT1 mm and 2-mm temporal, nasal, superior and inferior to the fovea were measured manually. RESULTS: RT in the inner temporal and nasal regionsdiffered significantly between refraction groups (both P<0.05). Significant differences were also found inSFCT andChT 1- and 2-mm inferior to the fovea (all P<0.05). RT differed significantly between males and females in the outer superior region in the emmetropia group (P<0.05). ChT differed significantly between males and females 2-mm temporal to the fovea in the emmetropia group (P<0.05), and 1-mm temporal to the fovea in the mild myopia group (P<0.05). SE correlated positively with RT in the inner temporal (r = 0.230),nasal (r = 0.252) and inferior (r = 0.149) regions (all P<0.05). Age correlated positively with foveolar (r = 0.169), total macular (r = 0.202), inner temporal (r = 0.237), inner nasal (r = 0.248), inner superior (r = 0.378) and inner inferior (r = 0.345) region thicknesses, and with RV (r = 0.207)(all P<0.05). SE correlated positively with SFCT (r = 0.195), and with ChT1-mm temporal (r = 0.167), 1- and 2-mm nasal (r = 0.144 and r = 0.162), 2-mm superior (r = 0.175), and 1- and 2-mm inferior (r = 0.207 and r = 0.238) to the fovea (all P<0.05). Age had no significant association with ChT. CONCLUSIONS: SE, age and gender did not influence macular RT and ChT in most regions, and correlations of RT with age and ChT with SE were weak. PMID- 27391016 TI - D-PLACE: A Global Database of Cultural, Linguistic and Environmental Diversity. AB - From the foods we eat and the houses we construct, to our religious practices and political organization, to who we can marry and the types of games we teach our children, the diversity of cultural practices in the world is astounding. Yet, our ability to visualize and understand this diversity is limited by the ways it has been documented and shared: on a culture-by-culture basis, in locally-told stories or difficult-to-access repositories. In this paper we introduce D-PLACE, the Database of Places, Language, Culture, and Environment. This expandable and open-access database (accessible at https://d-place.org) brings together a dispersed corpus of information on the geography, language, culture, and environment of over 1400 human societies. We aim to enable researchers to investigate the extent to which patterns in cultural diversity are shaped by different forces, including shared history, demographics, migration/diffusion, cultural innovations, and environmental and ecological conditions. We detail how D-PLACE helps to overcome four common barriers to understanding these forces: i) location of relevant cultural data, (ii) linking data from distinct sources using diverse ethnonyms, (iii) variable time and place foci for data, and (iv) spatial and historical dependencies among cultural groups that present challenges for analysis. D-PLACE facilitates the visualisation of relationships among cultural groups and between people and their environments, with results downloadable as tables, on a map, or on a linguistic tree. We also describe how D-PLACE can be used for exploratory, predictive, and evolutionary analyses of cultural diversity by a range of users, from members of the worldwide public interested in contrasting their own cultural practices with those of other societies, to researchers using large-scale computational phylogenetic analyses to study cultural evolution. In summary, we hope that D-PLACE will enable new lines of investigation into the major drivers of cultural change and global patterns of cultural diversity. PMID- 27391017 TI - Attentional Bias for Reward and Punishment in Overweight and Obesity: The TRAILS Study. AB - More than 80% of obese adolescents will become obese adults, and it is therefore important to enhance insight into characteristics that underlie the development and maintenance of overweight and obesity at a young age. The current study is the first to focus on attentional biases towards rewarding and punishing cues as potentially important factors. Participants were young adolescents (N = 607) who were followed from the age of 13 until the age of 19, and completed a motivational game indexing the attentional bias to general cues of reward and punishment. Additionally, self-reported reward and punishment sensitivity was measured. This study showed that attentional biases to cues that signal reward or punishment and self-reported reward and punishment sensitivity were not related to body mass index or the change in body mass index over six years in adolescents. Thus, attentional bias to cues of reward and cues of punishment, and self-reported reward and punishment sensitivity, do not seem to be crucial factors in the development and maintenance of overweight and obesity in adolescents. Exploratory analyses of the current study suggest that the amount of effort to gain reward and to avoid punishment may play a role in the development and maintenance of overweight and obesity. However, since the effort measure was a construct based on face validity and has not been properly validated, more studies are necessary before firm conclusions can be drawn. PMID- 27391018 TI - Switchable Liposomes: Targeting-Peptide-Functionalized and pH-Triggered Cytoplasmic Delivery. AB - One switchable nanodelivery system was constructed. Liposomes were functionalized by a novel dual-recognition peptide STP, which is pH-responsive as well as the affinity ligand of tumor marker VEGFR2 (the angiogenesis marker vascular endothelial growth factor receptor 2). Efficient drug delivery and in vivo therapy could be "turned on" and accelerated only in the conditions of VEGFR2 overexpression and a mild acidic environment. We envisioned that the successful demonstration of this switchable nanocarrier system would open a new avenue on rapid cytoplasmic delivery for specific cancer diagnostics and therapeutics. PMID- 27391019 TI - Viral RNase3 Co-Localizes and Interacts with the Antiviral Defense Protein SGS3 in Plant Cells. AB - Sweet potato chlorotic stunt virus (SPCSV; family Closteroviridae) encodes a Class 1 RNase III endoribonuclease (RNase3) that suppresses post-transcriptional RNA interference (RNAi) and eliminates antiviral defense in sweetpotato plants (Ipomoea batatas). For RNAi suppression, RNase3 cleaves double-stranded small interfering RNAs (ds-siRNA) and long dsRNA to fragments that are too short to be utilized in RNAi. However, RNase3 can suppress only RNAi induced by sense RNA. Sense-mediated RNAi involves host suppressor of gene silencing 3 (SGS3) and RNA dependent RNA polymerase 6 (RDR6). In this study, subcellular localization and host interactions of RNase3 were studied in plant cells. RNase3 was found to interact with SGS3 of sweetpotato and Arabidopsis thaliana when expressed in leaves, and it localized to SGS3/RDR6 bodies in the cytoplasm of leaf cells and protoplasts. RNase3 was also detected in the nucleus. Co-expression of RNase3 and SGS3 in leaf tissue enhanced the suppression of RNAi, as compared with expression of RNase3 alone. These results suggest additional mechanisms needed for efficient RNase3-mediated suppression of RNAi and provide new information about the subcellular context and phase of the RNAi pathway in which RNase3 realizes RNAi suppression. PMID- 27391020 TI - Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury. AB - Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated with or without SGLT2 inhibitor to investigate cell survival, the apoptosis signal pathway, and the induction of hypoxia-inducible factor 1 (HIF1) and associated proteins. Dapagliflozin improved renal function. Dapagliflozin reduced renal expression of Bax, renal tubule injury and TUNEL positive cells and increased renal expression of HIF1 in IR-injured mice. HIF1 inhibition by albendazole negated the renoprotective effects of dapagliflozin treatment in IR-injured mice. In vitro, dapagliflozin increased the expression of HIF1, AMP-activated protein kinase (AMPK), and ERK and increased cell survival of hypoxic HK2 cells in a dose-dependent manner. In conclusion, dapagliflozin attenuates renal IR injury. HIF1 induction by dapagliflozin may play a role in renoprotection against renal IR injury. PMID- 27391021 TI - Functional Characterization of the Osteoarthritis Susceptibility Mapping to CHST11-A Bioinformatics and Molecular Study. AB - The single nucleotide polymorphism (SNP) rs835487 is associated with hip osteoarthritis (OA) at the genome-wide significance level and is located within CHST11, which codes for carbohydrate sulfotransferase 11. This enzyme post translationally modifies proteoglycan prior to its deposition in the cartilage extracellular matrix. Using bioinformatics and experimental analyses, our aims were to characterise the rs835487 association signal and to identify the causal functional variant/s. Database searches revealed that rs835487 resides within a linkage disequilibrium (LD) block of only 2.7 kb and is in LD (r2 >= 0.8) with six other SNPs. These are all located within intron 2 of CHST11, in a region that has predicted enhancer activity and which shows a high degree of conservation in primates. Luciferase reporter assays revealed that of the seven SNPs, rs835487 and rs835488, which have a pairwise r2 of 0.962, are the top functional candidates; the haplotype composed of the OA-risk conferring G allele of rs835487 and the corresponding T allele of rs835488 (the G-T haplotype) demonstrated significantly different enhancer activity relative to the haplotype composed of the non-risk A allele of rs835487 and the corresponding C allele of rs835488 (the A-C haplotype) (p < 0.001). Electrophoretic mobility shift assays and supershifts identified several transcription factors that bind more strongly to the risk conferring G and T alleles of the two SNPs, including SP1, SP3, YY1 and SUB1. CHST11 was found to be upregulated in OA versus non-OA cartilage (p < 0.001) and was expressed dynamically during chondrogenesis. Its expression in adult cartilage did not however correlate with rs835487 genotype. Our data demonstrate that the OA susceptibility is mediated by differential protein binding to the alleles of rs835487 and rs835488, which are located within an enhancer whose target may be CHST11 during chondrogenesis or an alternative gene. PMID- 27391022 TI - Combining Costs and Benefits of Animal Activities to Assess Net Yield Outcomes in Apple Orchards. AB - Diverse animal communities influence ecosystem function in agroecosystems through positive and negative plant-animal interactions. Yet, past research has largely failed to examine multiple interactions that can have opposing impacts on agricultural production in a given context. We collected data on arthropod communities and yield quality and quantity parameters (fruit set, yield loss and net outcomes) in three major apple-growing regions in south-eastern Australia. We quantified the net yield outcome (accounting for positive and negative interactions) of multiple animal activities (pollination, fruit damage, biological control) across the entire growing season on netted branches, which excluded vertebrate predators of arthropods, and open branches. Net outcome was calculated as the number of undamaged fruit at harvest as a proportion of the number of blossoms (i.e., potential fruit yield). Vertebrate exclusion resulted in lower levels of fruit set and higher levels of arthropod damage to apples, but did not affect net outcomes. Yield quality and quantity parameters (fruit set, yield loss, net outcomes) were not directly associated with arthropod functional groups. Model variance and significant differences between the ratio of pest to beneficial arthropods between regions indicated that complex relationships between environmental factors and multiple animal interactions have a combined effect on yield. Our results show that focusing on a single crop stage, species group or ecosystem function/service can overlook important complexity in ecological processes within the system. Accounting for this complexity and quantifying the net outcome of ecological interactions within the system, is more informative for research and management of biodiversity and ecosystem services in agricultural landscapes. PMID- 27391023 TI - Mapping the Risk of Snakebite in Sri Lanka - A National Survey with Geospatial Analysis. AB - BACKGROUND: There is a paucity of robust epidemiological data on snakebite, and data available from hospitals and localized or time-limited surveys have major limitations. No study has investigated the incidence of snakebite across a whole country. We undertook a community-based national survey and model based geostatistics to determine incidence, envenoming, mortality and geographical pattern of snakebite in Sri Lanka. METHODOLOGY/PRINCIPAL FINDINGS: The survey was designed to sample a population distributed equally among the nine provinces of the country. The number of data collection clusters was divided among districts in proportion to their population. Within districts clusters were randomly selected. Population based incidence of snakebite and significant envenoming were estimated. Model-based geostatistics was used to develop snakebite risk maps for Sri Lanka. 1118 of the total of 14022 GN divisions with a population of 165665 (0.8%of the country's population) were surveyed. The crude overall community incidence of snakebite, envenoming and mortality were 398 (95% CI: 356-441), 151 (130-173) and 2.3 (0.2-4.4) per 100000 population, respectively. Risk maps showed wide variation in incidence within the country, and snakebite hotspots and cold spots were determined by considering the probability of exceeding the national incidence. CONCLUSIONS/SIGNIFICANCE: This study provides community based incidence rates of snakebite and envenoming for Sri Lanka. The within-country spatial variation of bites can inform healthcare decision making and highlights the limitations associated with estimates of incidence from hospital data or localized surveys. Our methods are replicable, and these models can be adapted to other geographic regions after re-estimating spatial covariance parameters for the particular region. PMID- 27391024 TI - Correction: Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin. AB - [This corrects the article DOI: 10.1371/journal.pone.0149100.]. PMID- 27391025 TI - The Interaction of CD154 with the alpha5beta1 Integrin Inhibits Fas-Induced T Cell Death. AB - CD154, a critical regulator of the immune response, is usually associated with chronic inflammatory, autoimmune diseases as well as malignant disorders. In addition to its classical receptor CD40, CD154 is capable of binding other receptors, members of the integrin family, the alphaIIbbeta3, alphaMbeta2 and alpha5beta1. Given the role attributed to integrins and particularly the beta1 integrins in inhibiting apoptotic events in normal as well as malignant T cells, we were highly interested in investigating the role of the CD154/alpha5beta1 interaction in promoting survival of malignant T cells contributing as such to tumor development and/or propagation. To support our hypothesis, we first show that soluble CD154 binds to the T-cell acute lymphoblastic leukemia cell line, Jurkat E6.1 in a alpha5beta1-dependent manner. Binding of soluble CD154 to alpha5beta1 integrin of Jurkat cells leads to the activation of key survival proteins, including the p38 and ERK1/2 mitogen-activated protein kinases (MAPKs), phosphoinositide 3 kinase (PI-3K), and Akt. Interestingly, soluble CD154 significantly inhibits Fas-mediated apoptosis in T cell leukemia-lymphoma cell lines, Jurkat E6.1 and HUT78 cells, an important hallmark of T cell survival during malignancy progression. These anti-apoptotic effects were mainly mediated by the activation of the PI-3K/Akt pathway but also involved the p38 and the ERK1/2 MAPKs cascades. Our data also demonstrated that the CD154-triggered inhibition of the Fas-mediated cell death response was dependent on a suppression of caspase-8 cleavage, but independent of de novo protein synthesis or alterations in Fas expression on cell surface. Together, our results highlight the impact of the CD154/alpha5beta1 interaction in T cell function/survival and identify novel targets for the treatment of malignant disorders, particularly of T cell origin. PMID- 27391027 TI - All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis. AB - BACKGROUND: Recently, the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL), but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL. METHODS: We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity. RESULTS: Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009), overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009), complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03). There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07). CONCLUSION: Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients. PMID- 27391026 TI - ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence. AB - Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract. PMID- 27391028 TI - Correlation between National Influenza Surveillance Data and Search Queries from Mobile Devices and Desktops in South Korea. AB - BACKGROUND: Digital surveillance using internet search queries can improve both the sensitivity and timeliness of the detection of a health event, such as an influenza outbreak. While it has recently been estimated that the mobile search volume surpasses the desktop search volume and mobile search patterns differ from desktop search patterns, the previous digital surveillance systems did not distinguish mobile and desktop search queries. The purpose of this study was to compare the performance of mobile and desktop search queries in terms of digital influenza surveillance. METHODS AND RESULTS: The study period was from September 6, 2010 through August 30, 2014, which consisted of four epidemiological years. Influenza-like illness (ILI) and virologic surveillance data from the Korea Centers for Disease Control and Prevention were used. A total of 210 combined queries from our previous survey work were used for this study. Mobile and desktop weekly search data were extracted from Naver, which is the largest search engine in Korea. Spearman's correlation analysis was used to examine the correlation of the mobile and desktop data with ILI and virologic data in Korea. We also performed lag correlation analysis. We observed that the influenza surveillance performance of mobile search queries matched or exceeded that of desktop search queries over time. The mean correlation coefficients of mobile search queries and the number of queries with an r-value of >= 0.7 equaled or became greater than those of desktop searches over the four epidemiological years. A lag correlation analysis of up to two weeks showed similar trends. CONCLUSION: Our study shows that mobile search queries for influenza surveillance have equaled or even become greater than desktop search queries over time. In the future development of influenza surveillance using search queries, the recognition of changing trend of mobile search data could be necessary. PMID- 27391029 TI - Molecular Relaxations in Supercooled Liquid and Glassy States of Amorphous Quinidine: Dielectric Spectroscopy and Density Functional Theory Approaches. AB - In this article, we conduct a comprehensive molecular relaxation study of amorphous Quinidine above and below the glass-transition temperature (Tg) through broadband dielectric relaxation spectroscopy (BDS) experiments and theoretical density functional theory (DFT) calculations, as one major issue with the amorphous state of pharmaceuticals is life expectancy. These techniques enabled us to determine what kind of molecular motions are responsible, or not, for the devitrification of Quinidine. Parameters describing the complex molecular dynamics of amorphous Quinidine, such as Tg, the width of the alpha relaxation (betaKWW), the temperature dependence of alpha-relaxation times (taualpha), the fragility index (m), and the apparent activation energy of secondary gamma relaxation (Ea-gamma), were characterized. Above Tg (> 60 degrees C), a medium degree of nonexponentiality (betaKWW = 0.5) was evidenced. An intermediate value of the fragility index (m = 86) enabled us to consider Quinidine as a glass former of medium fragility. Below Tg (< 60 degrees C), one well-defined secondary gamma relaxation, with an apparent activation energy of Ea-gamma = 53.8 kJ/mol, was reported. From theoretical DFT calculations, we identified the most reactive part of Quinidine moieties through exploration of the potential energy surface. We evidenced that the clearly visible gamma process has an intramolecular origin coming from the rotation of the CH(OH)C9H14N end group. An excess wing observed in amorphous Quinidine was found to be an unresolved Johari Goldstein relaxation. These studies were supplemented by sub-Tg experimental evaluations of the life expectancy of amorphous Quinidine by X-ray powder diffraction and differential scanning calorimetry. We show that the difference between Tg and the onset temperature for crystallization, Tc, which is 30 K, is sufficiently large to avoid recrystallization of amorphous Quinidine during 16 months of storage under ambient conditions. PMID- 27391031 TI - Social determinants of inequities in under-nutrition (weight-for-age) among under 5 children: a cross sectional study in Gumla district of Jharkhand, India. AB - BACKGROUND: Jharkhand, a state with substantial tribal population in Eastern India has very high rate of undernutrition. The study tries to understand the social determinants of inequities in under-nutrition (weight-for-age) among children aged less than 5 years, in Gumla District of the State. METHODS: Cross sectional study of 1070 children from 32 villages of 4 Blocks of Gumla District. RESULTS: 54.3 % (95 % CI 51.3-57.3) children were found to be underweight (less than -2SD), with insignificant difference between girls and boys. Multivariate analysis showed that poverty was the single most important predictor of undernutrition, where a child from the poorest quintile was 70 % more likely to be underweight (aOR 1.70, CI 1.13-2.57), compared to one from the least poor group (Quintile 5). While the difference in weight-for-age status between Scheduled Tribes and "OBC and other communities" was non-significant (95 % OR 1.12, CI 0.88-1.42) in the study context; community disaggregated data revealed that there were large variations within the tribal community, and numerically smaller communities also ranked lower in wealth, and their children showed poorer nutritional status. Other factors like maternal education beyond matriculation level also had some bearing. Bivariate analysis showed that chances of a child being underweight (<-2SD) was 43 % more and being severely underweight (<-3SD) was 26 % more for mothers with less than 10 years of schooling compared to those who had attended school for more than 10 years. Educational attainment of mothers did not show any significant difference between tribal and non-tribal communities. CONCLUSION: Overall nutritional status of children in Gumla is very grim and calls for immediate interventions, with universal coverage. Risk was almost equal for both genders, and for tribal and non-tribal population, though within tribal communities, it was slightly higher for smaller tribal communities, calling for soft targeting. Comprehensive programme addressing poverty and higher education for girls would be important to overcome the structural barriers, and should be integral part of any intervention. The study highlights the importance of soft targeting vulnerable communities within the universal coverage of government programmes for better nutritional outcomes. PMID- 27391030 TI - Involvement of DNMT 3B promotes epithelial-mesenchymal transition and gene expression profile of invasive head and neck squamous cell carcinomas cell lines. AB - BACKGROUND: The 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile. METHODS: Invasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 MUm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array. RESULTS: DNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5' region of E cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion. CONCLUSIONS: DNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation. PMID- 27391032 TI - How does the knowledge environment shape procurement practices for orthopaedic medical devices in Mexico? AB - BACKGROUND: In organisational theory there is an assumption that knowledge is used effectively in healthcare systems that perform well. Actors in healthcare systems focus on managing knowledge of clinical processes like, for example, clinical decision-making to improve patient care. We know little about connecting that knowledge to administrative processes like high-risk medical device procurement. We analysed knowledge-related factors that influence procurement and clinical procedures for orthopaedic medical devices in Mexico. METHODS: We based our qualitative study on 48 semi-structured interviews with various stakeholders in Mexico: orthopaedic specialists, government officials, and social security system managers or administrators. We took a knowledge-management related perspective (i) to analyse factors of managing knowledge of clinical procedures, (ii) to assess the role of this knowledge and in relation to procurement of orthopaedic medical devices, and (iii) to determine how to improve the situation. RESULTS: The results of this study are primarily relevant for Mexico but may also give impulsion to other health systems with highly standardized procurement practices. We found that knowledge of clinical procedures in orthopaedics is generated inconsistently and not always efficiently managed. Its support for procuring orthopaedic medical devices is insufficient. Identified deficiencies: leaders who lack guidance and direction and thus use knowledge poorly; failure to share knowledge; insufficiently defined formal structures and processes for collecting information and making it available to actors of health system; lack of strategies to benefit from synergies created by information and knowledge exchange. Many factors are related directly or indirectly to technological aspects, which are insufficiently developed. CONCLUSIONS: The content of this manuscript is novel as it analyses knowledge-related factors that influence procurement of orthopaedic medical devices in Mexico. Based on our results we recommend that the procurement mechanism should integrate knowledge from clinical procedures adequately in their decision-making. Without strong guidance, organisational changes, and support by technological solutions to improve the generation and management of knowledge, procurement processes for orthopaedic high-risk medical devices will remain sub-optimal. PMID- 27391034 TI - Hemodynamic deterioration precedes onset of ventricular tachyarrhythmia after Heartmate II implantation. AB - BACKGROUND: Early postoperative ventricular tachyarrhythmia (PoVT) after left ventricular assist device (LVAD) implantation are common and associated with higher mortality-rates. At present, there is no data on initiation of these PoVT and the role of alterations in cardiac hemodynamics. CASE PRESENTATION: A LVAD was implanted in a patient with end-stage heart failure due to a ischemic cardiomyopathy. Alterations in cardiac rhythm and hemodynamics preceding PoVT episodes during the first five postoperative days were examined by using continuous recordings of cardiac rhythm and various hemodynamic parameters. All PoVT (N=120) were monomorphic, most often preceded by short-long-short-sequences or regular SR and initiated by ventricular runs. Prior to PoVT, mean arterial pressure decreased; heart rate and ST-segments deviations increased. CONCLUSIONS: PoVT are caused by different underlying electrophysiological mechanisms. Yet, they are all monomorphic and preceded by hemodynamic deterioration due to myocardial ischemia. PMID- 27391033 TI - Association of sputum microbiota profiles with severity of community-acquired pneumonia in children. AB - BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay >= 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48-0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02-2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay >= 4 days [aOR 1.52; 95 % CI 1.02-2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. PMID- 27391036 TI - Multidisciplinary approaches to managing osteoarthritis in multiple joint sites: a systematic review. AB - BACKGROUND: The National Institute for Health and Care Excellence's Osteoarthritis (OA) guidelines recommended that future research should consider the benefits of combination therapies in people with OA across multiple joint sites. However, the clinical effectiveness of such approaches to OA management is unknown. This systematic review therefore aimed to identify the clinical and cost effectiveness of multidisciplinary approaches targeting multiple joint sites for OA in primary care. METHODS: A systematic review of randomised controlled trials. Computerised bibliographic databases were searched (MEDLINE, EMBASE, CINAHL, PsychINFO, BNI, HBE, HMIC, AMED, Web of Science and Cochrane). Studies were included if they met the following criteria; a randomised controlled trial (RCT), a primary care population with OA across at least two different peripheral joint sites (multiple joint sites), and interventions undertaken by at least two different health disciplines (multidisciplinary). The Cochrane 'Risk of Bias' tool and PEDro were used for quality assessment of eligible studies. Clinical and cost effectiveness was determined by extracting and examining self-reported outcomes for pain, function, quality of life (QoL) and health care utilisation. The date range for the search was from database inception until August 2015. RESULTS: The search identified 1148 individual titles of which four were included in the review. A narrative review was conducted due to the heterogeneity of the included trials. Each of the four trials used either educational or exercise interventions facilitated by a range of different health disciplines. Moderate clinical benefits on pain, function and QoL were reported across the studies. The beneficial effects of exercise generally decreased over time within all studies. Two studies were able to show a reduction in healthcare utilisation due to a reduction in visits to a physiotherapist or a reduction in x-rays and orthopaedic referrals. The intervention that showed the most promise used educational interventions delivered by GPs with reinforcement by practice nurses. CONCLUSIONS: There are currently very few studies that target multidisciplinary approaches suitable for OA across multiple joint sites, in primary care. A more consistent approach to outcome measurement in future studies of this nature should be considered to allow for better comparison. PMID- 27391035 TI - Exogenous calcium induces tolerance to atrazine stress in Pennisetum seedlings and promotes photosynthetic activity, antioxidant enzymes and psbA gene transcripts. AB - Calcium (Ca) has been reported to lessen oxidative damages in plants by upregulating the activities of antioxidant enzymes. However, atrazine mediated reactive oxygen species (ROS) reduction by Ca is limited. This study therefore investigated the effect of exogenously applied Ca on ROS, antioxidants activity and gene transcripts, the D1 protein (psbA gene), and chlorophyll contents in Pennisetum seedlings pre-treated with atrazine. Atrazine toxicity increased ROS production and enzyme activities (ascorbate peroxidase APX, peroxidase POD, Superoxide dismutase SOD, glutathione-S-transferase GST); but decreased antioxidants (APX, POD, and Cu/Zn SOD) and psbA gene transcripts. Atrazine also decreased the chlorophyll contents, but increased chlorophyll (a/b) ratio. Contrarily, Ca application to atrazine pre-treated seedlings lowered the harmful effects of atrazine by reducing ROS levels, but enhancing the accumulation of total chlorophyll contents. Ca-protected seedlings in the presence of atrazine manifested reduced APX and POD activity, whereas SOD and GST activity was further increased with Ca application. Antioxidant gene transcripts that were down regulated by atrazine toxicity were up-regulated with the application of Ca. Calcium application also resulted in up-regulation of the D1 protein. In conclusion, ability of calcium to reverse atrazine-induced oxidative damage and calcium regulatory role on GST in Pennisetum was presented. PMID- 27391037 TI - Treatment Outcome of Adolescent Inpatients With Early-Onset and Adolescent-Onset Disruptive Behavior. AB - OBJECTIVE: Unlike adolescents with adolescent-onset (AO) disruptive behavior, adolescents with early-onset (EO) disruptive behavior may not benefit from treatment. METHOD: Using Symptom Checklist (SCL-90-R) ratings at admission and discharge of adolescent inpatients with EO (n = 85) and AO (n = 60) disruptive behavior treatment outcome was determined by (a) a change in mean scores and (b) the Reliable Change Index. For a subgroup, ratings on the Satisfaction Questionnaire Residential Youth Care for Parents (n = 83) were used to verify the treatment outcome. RESULTS: Inpatients with EO disruptive behavior had a higher risk of dropout (44.4%) from treatment than the AO group (24.7%). Among the treatment completers, both onset groups reported improvements on the SCL-90-R, with 26.9% recovering and 31.7% improving. Inpatients who reported improvement were mostly rated as improved by their parents (r = .33). CONCLUSION: As EO inpatients are more likely to drop out, interventions should aim at motivating youngsters to continue treatment, particularly given the poor outcome in this group. Treatment may benefit both groups because those EO youths who stayed in treatment improved to the same extent as AO inpatients. PMID- 27391038 TI - Contact-active antibacterial aerogels from cellulose nanofibrils. AB - The use of cellulose aerogels as antibacterial materials has been investigated by applying a contact-active layer-by-layer modification to the aerogel surface. Studying the adsorption of multilayers of polyvinylamine (PVAm) and polyacrylic acid to aerogels comprising crosslinked cellulose nanofibrils and monitoring the subsequent bacterial adhesion revealed that up to 26mgPVAmgaerogel(-1) was adsorbed without noticeably affecting the aerogel structure. The antibacterial effect was tested by measuring the reduction of viable bacteria in solution when the aerogels were present. The results show that >99.9% of the bacteria adhered to the surface of the aerogels. Microscopy further showed adherence of bacteria to the surfaces of the modified aerogels. These results indicate that it is possible to create materials with three-dimensional cellulose structures that adsorb bacteria with very high efficiency utilizing the high specific surface area of the aerogels in combination with their open structure. PMID- 27391039 TI - N-Heterocyclic Carbene Catalyzed [4 + 2] Annulation Reactions with in Situ Generated Heterocyclic ortho-Quinodimethanes. AB - An efficient strategy for the in situ generation of heterocyclic ortho quinodimethanes (oQDMs) from 2-methyl-heteroarene-3-carboxylic esters by N heterocyclic carbene (NHC) catalysis is disclosed. These heterocyclic oQDMs undergo highly enantioselective [4 + 2] annulation reactions with isatin-derived ketimines to afford optically pure heteroarene-fused delta-lactams bearing a quaternary stereogenic center. The main features of this reaction include challenging direct C(sp(3))-H bond functionalizations, excellent enantioselectivities, readily available starting materials, mild reaction conditions, high efficiency, and operational simplicity. PMID- 27391041 TI - Heart-Rate Variability Threshold as an Alternative for Spiro-Ergometry Testing: A Validation Study. AB - Mankowski, RT, Michael, S, Rozenberg, R, Stokla, S, Stam, HJ, and Praet, SFE. Heart-rate variability threshold as an alternative for spiro-ergometry testing: a validation study. J Strength Cond Res 31(2): 474-479, 2017-Although spiro ergometry is the established "gold standard" for determination of the second ventilatory threshold (VT2), it is a costly and rather time-consuming method. Previous studies suggest that assessing the second anaerobic threshold (AT2) on the basis of heart rate variability (HRV) during exercise may be a more cost effective and noninvasive manner. However, appropriate validation studies, are still lacking. Eleven healthy, moderately trained subjects underwent 3 incremental exercise tests. Ventilation, oxygen uptake (V[Combining Dot Above]O2), CO2 production (V[Combining Dot Above]CO2), and HRV were measured continuously. Exercise testing was performed in 3 oxygen (FiO2) conditions of inspired air (14, 21, and 35% of oxygen). Participants and assessors were blinded to the FiO2 conditions. Two research teams assessed VT2s and HRVT2s independently from each other. Mean workloads corresponding to VT2 and HRVT2 in hypoxia were, respectively, 19 +/- 17% (p = 0.01) and 15 +/- 15% (p = 0.1) lower in comparison with hyperoxic conditions. Bland-Altman analysis showed low estimation bias (2.2%) and acceptably precise 95% limits of agreement for workload -15.7% to 20.1% for all FiO2 conditions. Bias was the lowest under normoxic conditions (1.1%) in comparison with hypoxia (3.7%) and hyperoxia (4.7%). Heart rate variability-based AT2 assessment had a most acceptable agreement with VT2 under normoxic conditions. This simple HRVT2 assessment may have potential applications for exercise monitoring in commercial fitness settings. PMID- 27391042 TI - CHESSSS: An Innovative Rorschach Scoring Program. PMID- 27391040 TI - Dipeptidyl peptidase-4 inhibition with linagliptin prevents western diet-induced vascular abnormalities in female mice. AB - BACKGROUND: Vascular stiffening, a risk factor for cardiovascular disease, is accelerated, particularly in women with obesity and type 2 diabetes. Preclinical evidence suggests that dipeptidylpeptidase-4 (DPP-4) inhibitors may have cardiovascular benefits independent of glycemic lowering effects. Recent studies show that consumption of a western diet (WD) high in fat and simple sugars induces aortic stiffening in female C57BL/6J mice in advance of increasing blood pressure. The aims of this study were to determine whether administration of the DPP-4 inhibitor, linagliptin (LGT), prevents the development of aortic and endothelial stiffness induced by a WD in female mice. METHODS: C56Bl6/J female mice were fed a WD for 4 months. Aortic stiffness and ex vivo endothelial stiffness were evaluated by Doppler pulse wave velocity (PWV) and atomic force microscopy (AFM), respectively. In addition, we examined aortic vasomotor responses and remodeling markers via immunohistochemistry. Results were analyzed via 2-way ANOVA, p < 0.05 was considered as statistically significant. RESULTS: Compared to mice fed a control diet (CD), WD-fed mice exhibited a 24 % increase in aortic PWV, a five-fold increase in aortic endothelial stiffness, and impaired endothelium-dependent vasodilation. In aorta, these findings were accompanied by medial wall thickening, adventitial fibrosis, increased fibroblast growth factor 23 (FGF-23), decreased Klotho, enhanced oxidative stress, and endothelial cell ultrastructural changes, all of which were prevented with administration of LGT. CONCLUSIONS: The present findings support the notion that DPP-4 plays a role in development of WD-induced aortic stiffening, vascular oxidative stress, endothelial dysfunction, and vascular remodeling. Whether, DPP-4 inhibition could be a therapeutic tool used to prevent the development of aortic stiffening and the associated cardiovascular complications in obese and diabetic females remains to be elucidated. PMID- 27391043 TI - Census tract based income level and lipid levels in urban pediatric primary care: a retrospective study. AB - BACKGROUND: Lower socioeconomic status has been associated with adverse lipid levels in adult populations. Childhood dyslipidemia is a risk factor for future cardiovascular disease. However, studies examining relationships between socioeconomic indicators and lipid levels in children are limited. To examine the relationship between income level and lipid levels in childhood. METHODS: We conducted a retrospective chart review of primary care patients, ages 2 to 18 years, who had lipid levels drawn at two large pediatric practices in Boston, MA between August 01, 2008 and August 31, 2010. Income level was determined using geocoding census tract data. Analysis was performed using t-test, Anova and Spearman correlation coefficients. BMI percentile, age, sex, race/ethnicity, and site were adjusted for on multivariate analyses. RESULTS: Reviewing 930 charts of patients with measured lipid levels, 730 had a valid address, no previously diagnosed lipid disorder and met other study eligibility criteria. Mean total cholesterol level did not vary by income level (low 155.5 mg/dl +/-26.9, moderate 153.5 mg/dl +/-30.4, middle 155.3 mg/dl +/-26.6 and high income 155.5 mg/dl +/ 27.9; p = .87) on multivariate analysis. Income level was not related to LDL, HDL, or triglycerides. CONCLUSIONS: In this analysis of children cared for in two urban pediatric primary practices, there was no association between income level determined by census tract and lipid levels in childhood. If confirmed in prospective investigations in other geographical locations, income level may not be a key driver of childhood lipid levels. PMID- 27391044 TI - Young smoker "ABCD" vascular assessment: a four-step ultrasound examination for detecting peripheral, extra and intra-cranial early arterial damage. AB - BACKGROUND: Cigarette smoking is known as a major risk factor in the pathogenic mechanisms of stroke, coronary and peripheral artery disease (CAD and PAD), even in young subjects. The aim of this study is the creation of a four-step ultrasound examination to evaluate and monitor the peripheral, the extra and the intra-cranial assessment of the arterial early damage in smokers. The evaluations of A, the Ankle-brachial index, ABI, B, the Breath holding index, BHI, C, the Carotid intima media thickness, CIMT, and D, the Diameter of the abdominal aorta represent the "ABCD" assessment. METHODS: Thirty-eight healthy smokers and 43 controls underwent A, calculated for each leg. B was calculated after determination of subjects' flow velocity of middle cerebral artery (MCA) by trans cranial colour Doppler (TCCD) before and after 30 s of apnoea at baseline and just after smoking a cigarette, to simulate the chronic and acute effects of smoking. Finally, C and D evaluation were assessed using a high-resolution B-mode ultrasound. RESULTS: Smokers presented higher values of CIMT (mean and maximal), and lower BHI both at baseline and just after smoking (p < 0.01), though in the normal range. No significant differences were found for A and D between smokers and non- smokers. CONCLUSIONS: Our results underline the importance of the assessment of B and C, that, though in the normal range, present significant differences between smokers and non-smokers. These data could drive the screening between smokers in age-related manner. Moreover, the "ABCD" examination could represent a valid method to detect and then monitor smokers' vascular damage. Although it is far to be considered a screening and routine tool, it should be contemplated in a wider context of possible not-invasive practical screening and follow-up modalities. This would be designed to implement preventive strategies and tools aimed at discouraging tobacco addiction and monitoring cardiovascular risk patients. PMID- 27391046 TI - Insecticidal activity of novel thioureas and isothioureas. AB - BACKGROUND: We hypothesized that the exploration of chemical space around compounds with reported insecticidal activity could be a viable strategy for discovering novel, insecticidally active areas of chemistry. RESULTS: A series of thioureas and isothioureas were prepared as part of a scaffold-hopping effort around known insecticidal compounds. Many of these compounds showed excellent activity against key sap-feeding insect pests in insecticidal bioassays. While analogs bearing monocyclic thiophene head groups showed activity against Myzus persicae (green peach aphid), analogs with diarylethane head groups were active against both M. persicae and Bemisia tabaci (sweetpotato whitefly). Despite compelling activity in these laboratory tests, these compounds showed diminished activity when applied to host plants via tracksprayer. CONCLUSIONS: The initial hypothesis that structural modification of molecules reported to have insecticidal activity would yield novel compounds that also exhibit insecticidal activity was validated. Despite excellent activity in laboratory bioassays, these new compounds failed to show compelling activity in more demanding tracksprayer tests. (c) 2016 Society of Chemical Industry. PMID- 27391045 TI - The Associations between Various Ectopic Visceral Adiposity and Body Surface Electrocardiographic Alterations: Potential Differences between Local and Remote Systemic Effects. AB - BACKGROUND: The associations between pericardial adiposity and altered atrial conduction had been demonstrated. However, data comparing differential effects of various body sites visceral adiposity on atrial and ventricular electrocardiographic alterations remains largely unknown. METHODS AND RESULTS: We assessed both peri-cardial fat (PCF) and peri-aortic visceral adiposity (TAT) using dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA), with anthropometrics including body mass index (BMI) and biochemical data obtained. We further related PCF and TAT data to standardized 12-leads electrocardiogram (ECG), including P and QRS wave morphologies. Among 3,087 study subjects (mean age, 49.6 years; 28% women), we observed a linear association among greater visceral adiposity burden, leftward deviation of P and QRS axes, longer PR interval and widened QRS duration (all p<0.001). These associations became attenuated after accounting for BMI and baseline clinical co-variates, with greater PCF remained independently associated with prolonged QRS duration (beta = 0.91 [95% CI: 0.52, 1.31] per 1-SD increase in PCF, p<0.001). Finally, both PCF and TAT showed incremental value in identifying abnormally high PR interval (>200ms, likelihood-ratio: 33.17 to 41.4 & 39.03 for PCF and TAT) and widened QRS duration (>100ms, likelihood-ratio: 55.67 to 65.4 & 61.94 for PCF and TAT, all X2 p<0.05) when superimposed on age and BMI. CONCLUSION: We show in our data greater visceral fat burden may have differential associations on several body surface electrocardiographic parameters. Compared to remote adiposity, those surrounding the heart tissue demonstrated greater influences on altered cardiac activation or conduction, indicating a possible local biological effect. PMID- 27391048 TI - The effect of bullet removal and vegetation on mobility of Pb in shooting range soils. AB - Lead (Pb) contamination at shooting ranges is a public health concern because Pb is a toxic metal. An experiment was conducted to determine the effect of two best management practices; bullet removal and vegetation, on bioavailability and leachability of Pb in three shooting range (SR) soils. St. Augustine grass was grown in sieved (2 mm) and un-sieved SR soils for 8 weeks after which leachates, soil and plant samples were analyzed. Bullet removal reduced total soil Pb, increased Mehlich-3 Pb in unvegetated soils and increased dissolved organic carbon (DOC) in all soils. Bullet removal increased leaching in two SR soils while grasses reduced leaching but increased water soluble Pb in two SR soils. The roots of the grasses were able to accumulate more Pb in the root (1893-5021 mg kg(-1)) than the aboveground biomass (252-880 mg kg(-1)) due to mobilization of Pb in the rhizosphere. Grasses had a higher plant biomass in unsieved soils suggesting tolerance to the presence of bullets in the unsieved soils. Results suggest that bullet removal probably increased microbial activity and Pb bioavailability in the soil. The leaching and bioavailability of Pb in shooting range soils depends on biological activities and chemical processes in the soil. PMID- 27391047 TI - Protein Adsorption as a Key Mediator in the Nanotopographical Control of Cell Behavior. AB - Surface nanotopography is widely employed to control cell behavior and in particular controlled disorder has been shown to be important in cell differentiation/maturation. However, extracellular matrix proteins, such as fibronectin (FN), initially adsorbed on a biomaterial surface are known to mediate the interaction of synthetic materials with cells. In this work, we examine the effect of nanotopography on cell behavior through this adsorbed layer of adhesive proteins using a nanostructured polycarbonate surface comprising 150 nm-diameter pits originally defined using electron beam lithography. We address the effect of this nanopitted surface on FN adsorption and subsequently on cell morphology and behavior using C2C12 myoblasts. Wettability measurements and atomic force microscopy imaging showed that protein is adsorbed both within the interpits spaces and inside the nanopits. Cells responded to this coated nanotopography with the formation of fewer but larger focal adhesions and by mimicking the pit patterns within their cytoskeleton, nanoimprinting, ultimately achieving higher levels of myogenic differentiation compared to a flat control. Both focal adhesion assembly and nanoimprinting were found to be dependent on cell contractility and are adversely affected by the use of blebbistatin. Our results demonstrate the central role of the nanoscale protein interface in mediating cell-nanotopographical interactions and implicate this interface as helping control the mechanotransductive cascade. PMID- 27391049 TI - Degradation of some representative polycyclic aromatic hydrocarbons by the water soluble protein extracts from Zea mays L. cv PR32-B10. AB - The ability of the water-soluble protein extracts from Zea mais L. cv. PR32-B10 to degrade some representative polycyclic aromatic hydrocarbons (PAHs), has been evaluated. Surface sterilized seeds of corn (Zea mais L. Pioneer cv. PR32-B10) were hydroponically cultivated in a growth chamber under no-stressful conditions. The water-soluble protein extracts isolated from maize tissues showed peroxidase, polyphenol oxidase and catalase activities. Incubation of the extracts with naphthalene, fluorene, phenanthrene and pyrene, led to formation of oxidized and/or degradation products. GC-MS and TLC monitoring of the processes showed that naphthalene, phenanthrene, fluorene and pyrene underwent 100%, 78%, 92% and 65% oxidative degradation, respectively, after 120 min. The chemical structure of the degradation products were determined by (1)H NMR and ESI-MS spectrometry. PMID- 27391050 TI - Determination of diffusion coefficients of biocides on their passage through organic resin-based renders. AB - In this study the diffusion coefficients of isoproturon, diuron and cybutryn in acrylate and silicone resin-based renders were determined. The diffusion coefficients were determined using measuring concentrations of biocides in the liquid phase after being in contact with renders for specific time intervals. The mathematical solution of the transient diffusion equation for an infinite plate contacted on one side with a limited volume of water was used to calculate the diffusion coefficient. The diffusion coefficients through the acrylate render were 8.10.10(-9) m(2) s(-1) for isoproturon, 1.96.10(-9) m(2) s(-1) for diuron and 1.53.10(-9) m(2) s(-1) for cybutryn. The results for the silicone render were lower by one order of magnitude. The compounds with a high diffusion coefficient for one polymer had likewise high values for the other polymer. PMID- 27391051 TI - Impact of biochar amendment on soil water soluble carbon in the context of extreme hydrological events. AB - Biochar amendments to soil have been promoted as a low cost carbon (C) sequestration strategy as well as a way to increase nutrient retention and remediate contaminants. If biochar is to become part of a long-term management strategy, it is important to consider its positive and negative impacts, and their trade-offs, on soil organic matter (SOM) and soluble C under different hydrological conditions such as prolonged drought or frequent wet-dry cycles. A 52-week incubation experiment measuring the influence of biochar on soil water soluble C under different soil moisture conditions (wet, dry, or wet-dry cycles) indicated that, in general, dry and wet-dry cycles increased water soluble C, and biochar addition further increased release of water soluble C from native SOM. Biochar amendment appeared to increase transformation of native SOM to water soluble C, based on specific ultraviolet absorption (SUVA) and C stable isotope composition; however, the increased amount of water soluble C from native SOM is less than 1% of total biochar C. The impacts of biochar on water soluble C need to be carefully considered when applying biochar to agricultural soil. PMID- 27391052 TI - Coping with seawater acidification and the emerging contaminant diclofenac at the larval stage: A tale from the clam Ruditapes philippinarum. AB - Seawater acidification could alter the susceptibility of marine organisms to emerging contaminants, such as pharmaceuticals. In this study, the combined effects of seawater acidification and the non-steroidal anti-inflammatory drug diclofenac on survival, growth and oxidative stress-related parameters (catalase activity and lipid peroxidation) in the larvae of the Manila clam Ruditapes philippinarum were investigated for the first time. An experimental flow-through system was set up to carry out a 96-h exposure of clam larvae. Two pH levels (pH 8.0, the control, and pH 7.8, the predicted pH by the end of this century) were tested with and without diclofenac (0.5 MUg/L). After 4 days, mortality was dramatically higher under reduced pH, particularly in the presence of diclofenac (62% of the larvae dead). Shell morphology was negatively affected by both acidification and diclofenac from the first day of exposure. The percentage of abnormal larvae was always higher at pH 7.8 than in controls, peaking at 98% in the presence of diclofenac after 96 h. Instead, shell length, shell height or the ratio of these values were only negatively influenced by reduced pH throughout the whole experiment. After 96 h, catalase activity was significantly increased in all larvae kept at pH 7.8, whereas no significant difference in lipid peroxidation was found among the treatments. This study demonstrates a high susceptibility of R. philippinarum larvae to a slight reduction in seawater pH. Furthermore, the results obtained highlight that acidification enhances the sensitivity of clam larvae to environmentally relevant concentrations of diclofenac. PMID- 27391053 TI - Assessing spatial and temporal variability of acid-extractable organics in oil sands process-affected waters. AB - The acid-extractable organic compounds (AEOs), including naphthenic acids (NAs), present within oil sands process-affected water (OSPW) receive great attention due to their known toxicity. While recent progress in advanced separation and analytical methodologies for AEOs has improved our understanding of the composition of these mixtures, little is known regarding any variability (i.e., spatial, temporal) inherent within, or between, tailings ponds. In this study, 5 samples were collected from the same location of one tailings pond over a 2-week period. In addition, 5 samples were collected simultaneously from different locations within a tailings pond from a different mine site, as well as its associated recycling pond. In both cases, the AEOs were analyzed using SFS, ESI MS, HRMS, GC*GC-ToF/MS, and GC- & LC-QToF/MS (GC analyses following conversion to methyl esters). Principal component analysis of HRMS data was able to distinguish the ponds from each other, while data from GC*GC-ToF/MS, and LC- and GC-QToF/MS were used to differentiate samples from within the temporal and spatial sample sets, with the greater variability associated with the latter. Spatial differences could be attributed to pond dynamics, including differences in inputs of tailings and surface run-off. Application of novel chemometric data analyses of unknown compounds detected by LC- and GC-QToF/MS allowed further differentiation of samples both within and between data sets, providing an innovative approach for future fingerprinting studies. PMID- 27391054 TI - Relationship of ambient air pollutants and hazardous household factors with birth weight among Bedouin-Arabs. AB - BACKGROUND: Air pollution and meteorology exposures during pregnancy have been suggested to be associated with Birth Weight (BW). Yet, the individual medical background and close household environment is rarely addressed. We aimed to evaluate the independent association of BW with meteorological and air pollution exposures during pregnancy, in addition to individual, parental and household risk factors, among the Bedouin-Arab population in Southern Israel; a semi nomadic population, featured by low socio-economic levels and poor housing and household environment. METHODS: In a retrospective cohort study we enrolled pregnant women upon their arrival in the local hospital for delivery during December 2011-April 2013. We interviewed the women and collected data on socio demographic characteristics, medical history and household environmental hazards. Air pollution (NO2, SO2, CO, Ozone and Particulate Matter <2.5 MU and 10 MU in diameter) and meteorological data (temperature, relative humidity), retrieved from 13 monitoring sites, were linked to each woman based on the proximity of her residential address. RESULTS: A total of 959 women were eligible for the study, half of them resided in temporary tribal localities. Ozone IQR elevation in the 3rd trimester was associated with 0.119 gr decrease in BW (95%CI -0.127 gr; 0.112 gr); temperature IQR elevation in the 3rd trimester was associated with 0.002 gr (95%CI -0.004 gr; -0.001 gr) decrease in BW. Waste in the house surroundings was associated with a decrease of 117.27 gr in BW (95%CI -209.19 gr; -25.34 gr). CONCLUSION: Although exposure to high levels of temperature and O3 were associated with lower BW, the contribution of poor household environment indicators to BW reduction was substantially higher. PMID- 27391055 TI - Decreased function of Fas and variations of the perforin gene in adult patients with primary immune thrombocytopenia. AB - A defective switching off of the immune response is involved in several autoimmune diseases. This switching off involves Fas-mediated apoptosis, perforin mediated fratricide of activated lymphocytes, and the suppressive activity of regulatory T (Treg) cells. These mechanisms are altered in autoimmune lymphoproliferative syndrome that often displays autoimmune thrombocytopenia. The aim of this research was to evaluate these mechanisms in adult patients with primary immune thrombocytopenia (ITP), compared with healthy controls. The results show that a substantial subgroup of the ITP patients displayed a defective Fas function; most of them displayed decreased Fas expression in T cells activated in vitro. Moreover, ITP patients displayed an increased frequency of rare missense variations of the PRF1 gene and decreased levels of Treg. Immunological analysis showed that levels of Interleukin (IL)10 and IL17 were decreased and marginal zone B cells were increased. Moreover, myeloid and plasmacytoid dendritic cells were decreased in ITP patients. In conclusion, in adult ITP patients, several mechanisms involved in shutting off the immune response are defective and several immunological parameters are dysregulated; these alterations may play a role in the clinical heterogeneity of the disease. PMID- 27391056 TI - Effect of resorption rate and osteoconductivity of biodegradable calcium phosphate materials on the acquisition of natural bone strength in the repaired bone. AB - The purpose of this study was to compare the biodegradation rate and quality of regenerated bone among four materials. A short time period of 8 weeks was chosen to examine early bone healing. The rod-shaped implants of commercially available two beta-tricalcium phosphate (beta-TCP) ceramics with porosity 60% and 71-80%, respectively, laboratory prepared octacalcium phosphate/gelatin composite (OCP/Gel), which has been proven to have a highly osteoconductive and biodegradable property in rat calvarial defect, and gelatin sponge (Gelatin) were implanted in rabbit tibia defect of 6 mm diameter and 7 mm depth for 2, 4 and 8 weeks. Analyses by MUCT, histomorphometry and push-in test were carried out to evaluate the extent of the tissue regeneration and the material biodegradation in the long bone. OCP/Gel and Gelatin were completely resorbed but only OCP/Gel induced cortical bone bridge until 8 weeks that has strength compatible to that of the natural bone. beta-TCP (71%-80%) and beta-TCP (60%) were not completely resorbed and never induced the amount of new bone formation beyond that by OCP/Gel. The results indicate that the new bone having enough strength could be regenerated if the material shows not only higher biodegradation rate but also higher osteoconductivity. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2833-2842, 2016. PMID- 27391057 TI - Use of Cusp Catastrophe for Risk Analysis of Navigational Environment: A Case Study of Three Gorges Reservoir Area. AB - A water traffic system is a huge, nonlinear, complex system, and its stability is affected by various factors. Water traffic accidents can be considered to be a kind of mutation of a water traffic system caused by the coupling of multiple navigational environment factors. In this study, the catastrophe theory, principal component analysis (PCA), and multivariate statistics are integrated to establish a situation recognition model for a navigational environment with the aim of performing a quantitative analysis of the situation of this environment via the extraction and classification of its key influencing factors; in this model, the natural environment and traffic environment are considered to be two control variables. The Three Gorges Reservoir area of the Yangtze River is considered as an example, and six critical factors, i.e., the visibility, wind, current velocity, route intersection, channel dimension, and traffic flow, are classified into two principal components: the natural environment and traffic environment. These two components are assumed to have the greatest influence on the navigation risk. Then, the cusp catastrophe model is employed to identify the safety situation of the regional navigational environment in the Three Gorges Reservoir area. The simulation results indicate that the situation of the navigational environment of this area is gradually worsening from downstream to upstream. PMID- 27391058 TI - CDK4/6 inhibition: the late harvest cycle begins. PMID- 27391059 TI - A novel pathogenic large germline deletion in adenomatous polyposis coli gene in a Chinese family with familial adenomatous polyposis. AB - Germline mutations of the APC gene are associated with an autosomal dominant precancerous condition, termed familial adenomatous polyposis (FAP). FAP is clinically manifested by the presence of multiple colorectal adenomas or polyps. Gradually, these colorectal adenomas or polyps inevitably result in colorectal cancer by the third-to fourth decade of life. Surgical interventions or total proctocolectomy is the best possible treatment for FAP. Here, we present a clinical molecular study of a five generation Chinese family with FAP. Diagnosis of FAP was made on the basis of clinical manifestations, family history and medical (colonoscopy and histopathology) records. Blood samples were collected and genomic DNA was extracted. Genetic screening of the APC gene was performed by targeted next-generation sequencing and quantitative real-time PCR. Targeted next generation sequencing identified a novel heterozygous large deletion [exon5 exon16; c.423_8532del] of APC gene, which segregated with the FAP phenotypes in the proband and in all the affected family members. Unaffected family members and normal controls did not carry this deletion. In the Chinese population, most of the previously reported APC gene mutations are missense mutations. This is the first report describing the largest deletion of the APC gene in the Chinese population associated with FAP. PMID- 27391060 TI - Inhibition of canonical WNT/beta-catenin signaling is involved in leflunomide (LEF)-mediated cytotoxic effects on renal carcinoma cells. AB - Leflunomide (LEF), an inhibitor of dihydroorotate dehydrogenase (DHODH) in pyrimidine biosynthetic pathway, is an immunomodulatory agent approved for the treatment of rheumatoid arthritis. In this study, we show that LEF significantly reduced cell proliferation of renal carcinoma cells in a concentration-dependent manner. LEF at 50 MUM induced S-phase arrest and autophagy. Higher doses of LEF (>50 MUM) effectively induced cell apoptosis. Modulating the concentration of LEF resulted in distinct effects on the expression of regulatory proteins associated with cell cycle, apoptosis, and autophagy. In particular, high concentrations of LEF inhibited canonical WNT signaling by promoting nucleo-cytoplasmic shuttling and proteasome-dependent degradation of beta-catenin. Mechanistic studies showed that the repression of AKT activation partly accounted for LEF-mediated WNT inhibition. Gene expression microarray revealed that LEF treatment greatly inhibited the expression of FZD10 gene, a receptor mediating WNT/beta-catenin activation. In vivo xenograft study in NOD/SCID mice further validated the inhibitory effects of LEF on tumor growth and Wnt/beta-catenin signaling. However, LEF treatment also triggered cell autophagy and elevated the expression of WNT3a, which ameliorated its cytotoxic effects. The combination of LEF with a WNT inhibitor IWP-2 or autophagy inhibitor HCQ could yield an enhanced anti-tumor outcome. Taken together, these results identify the potential utility and pharmacological feature of LEF in the chemotherapy of renal cell carcinoma (RCC). PMID- 27391061 TI - Triptolide inhibits cell growth and GRP78 protein expression but induces cell apoptosis in original and radioresistant NPC cells. AB - The radioresistance is the key factor to hamper curative effect and survival of nasopharyngeal carcinoma (NPC) patients. Nature triptolide (TPL) has been found to circumvent drug-resistant effect of cancer, but its effect on NPC radioresistance has been rarely studied. In the present study, the 10 Gy resistant CNE2 subclones (CNE2-SR) were used as a NPC radioresistant model. The IC50 of TPL in CNE2 and CNE2-SR cells was measured by MTT assay, cell cycle was analyzed by flow cytometry, and protein expression was examined by western blot. Our data showed that TPL treatment decreased the percentage of viable cells, and IC50 value in CNE2 and CNE2-SR cells was 23.6 +/- 1.41 nmol/L and 31.2 +/- 1.16 nmol/L, respectively. Six Gy was a moderate dosage of X-ray for CNE2, and 25 nM TPL was close to IC50 value of CNE2 and CNE2-SR. Six Gy X-ray and/or 25 nM TPL significantly inhibited tumor growth in nude mice. Furthermore, 6 Gy X-ray and/or 25 nM TPL significantly inhibited cell growth and induced cell apoptosis and M/G2 phase arrest in CNE2 and CNE2-SR cells. Moreover, TPL treatment significantly inhibited the expression of GRP78 protein in CNE2 and CNE2-SR cells. These results suggest that TPL may serve as a potential radiosensitizer agent for NPC treatment. PMID- 27391062 TI - Reactivation of ERK and Akt confers resistance of mutant BRAF colon cancer cells to the HSP90 inhibitor AUY922. AB - Oncogenic mutations of BRAF occur in approximately 10% of colon cancers and are associated with their resistance to clinically available therapeutic drugs and poor prognosis of the patients. Here we report that colon cancer cells with mutant BRAF are also resistant to the heat shock protein 90 (HSP90) inhibitor AUY922, and that this is caused by rebound activation of ERK and Akt. Although AUY922 triggered rapid reduction in ERK and Akt activation in both wild-type and mutant BRAF colon cancer cells, activation of ERK and Akt rebounded shortly in the latter leading to resistance of the cells to AUY922-induced apoptosis. Reactivation of ERK was associated with the persistent expression of mutant BRAF, which, despite being a client of HSP90, was only partially degraded by AUY922, whereas reactivation of Akt was related to the activity of the HSP90 co chaperone, cell division cycle 37 (CDC37), in that knockdown of CDC37 inhibited Akt reactivation in mutant colon cancer cells treated with AUY922. In support, as a HSP90 client protein, Akt was only diminished by AUY922 in wild-type but not mutant BRAF colon cancer cells. Collectively, these results reveal that reactivation of ERK and Akt associated respectively with the activity of mutant BRAF and CDC37 renders mutant BRAF colon cancer cells resistant to AUY922, with implications of co-targeting mutant BRAF and/or CDC37 and HSP90 in the treatment of mutant BRAF colon cancers. PMID- 27391063 TI - Transcriptome-wide characterization of the endogenous miR-34A-p53 tumor suppressor network. AB - microRNA-34A is a critical component of the p53 network and expression of miR- 34A is down-regulated by promoter hypermethylation or focal deletions in numerous human cancers. Although miR-34A deregulation may be an important driver in cancer, the endogenous role of this microRNA in cellular homeostasis is not well characterized. To address this knowledge gap, we aimed to determine the transcriptional landscape of the miR-34A-p53 axis in non-transformed cells. Using primary skin-derived fibroblast cell lines from patients who developed childhood cancers, and who harbor either germline TP53 mutations or are TP53 wild type, we sought to characterize the transcriptional response to miR-34A modulation. Through transcriptome-wide RNA-Sequencing, we show for the first time that in human non- transformed cells harboring TP53 mutations, miR-34A functions in a noncanonical manner to influence noncoding RNA networks, including RNA components of the minor (U12) spliceosome, as well as TP53-dependent and independent epigenetic pathways. miR- 34A-regulated transcripts include known cell cycle mediators and abrogation of miR-34A leads to a TP53-dependent increase in the fraction of cells in G2/M. Collectively, these results provide a framework for understanding the endogenous role of the miR-34A signaling axis and identify novel transcripts and pathways regulated by the essential miR-34A-p53 tumor suppressor network. PMID- 27391064 TI - In-depth proteomic profiling of the uveal melanoma secretome. AB - Uveal melanoma (UM), the most common primary intraocular tumour in adults, is characterised by a high frequency of metastases to the liver, typically with a fatal outcome. Proteins secreted from cancer cells ('secretome') are biologically important molecules thought to contribute to tumour progression. We examined the UM secretome by applying a label-free nanoLCMS/MS proteomic approach to profile proteins secreted into culture media by primary UM tumours with a high- (HR; n = 11) or low- (LR; n = 4) metastatic risk, compared to normal choroidal melanocytes (NCM) from unaffected post-mortem eyes. Across the three groups, 1843 proteins were identified at a 1% false discovery rate; 758 of these by at least 3 unique peptides, and quantified. The majority (539/758, 71%) of proteins were classified as secreted either by classical (144, 19%), non-classical (43, 6%) or exosomal (352, 46%) mechanisms. Bioinformatic analyzes showed that the secretome composition reflects biological differences and similarities of the samples. Ingenuity(r) pathway analysis of the secreted protein dataset identified abundant proteins involved in cell proliferation-, growth- and movement. Hepatic fibrosis/hepatic stellate cell activation and the mTORC1-S6K signalling axis were among the most differentially regulated biological processes in UM as compared with NCM. Further analysis of proteins upregulated >= 2 in HR-UM only, identified exosomal proteins involved in extracellular matrix remodelling and cancer cell migration/invasion; as well as classically secreted proteins, possibly representing novel biomarkers of metastatic disease. In conclusion, UM secretome analysis identifies novel proteins and pathways that may contribute to metastatic development at distant sites, particularly in the liver. PMID- 27391065 TI - Metformin as a new anti-cancer drug in adrenocortical carcinoma. AB - Adrenocortical carcinoma (ACC) is a rare heterogeneous malignancy with poor prognosis. Since radical surgery is the only available treatment, more specific and effective drugs are urgently required. The anti-diabetic drug metformin has been associated with a decreased cancer prevalence and mortality in several solid tumors, prompting its possible use for ACC treatment.This paper evaluates the in vitro and in vivo anti-cancer effects of metformin using the ACC cell model H295R.Metformin treatment significantly reduces cell viability and proliferation in a dose- and time-dependent manner and associates with a significant inhibition of ERK1/2 and mTOR phosphorylation/activation, as well as with stimulation of AMPK activity. Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector. Metformin interferes with the proliferative autocrine loop of IGF2/IGF-1R, which supports adrenal cancer growth. Finally, in the ACC xenograft mouse model, obtained by subcutaneous injection of H295R cells, metformin intraperitoneal administration inhibits tumor growth, confirmed by the significant reduction of Ki67%.Our data suggest that metformin inhibits H295R cell growth both in vitro and in vivo. Further preclinical studies are necessary to validate the potential anti-cancer effect of metformin in patients affected by ACC. PMID- 27391066 TI - miR-130b, an onco-miRNA in bladder cancer, is directly regulated by NF-kappaB and sustains NF-kappaB activation by decreasing Cylindromatosis expression. AB - Persistent activation of NF-kappaB signaling is closely related to chronic inflammation and tumorigenesis. Commonly, NF-kappaB signaling is tightly controlled by multiple feedback loops and regulators, such as the deubiquitinases (DUBs). However, in cancer cells, NF-kappaB may override these feedbacks through special pathways and lead to the sustained activation. In the present study, we demonstrate that in transitional cell carcinoma (TCC) of bladder, miR-130b plays an oncogenesis role, it enhanced proliferation, invasion and migration of TCC cell, and was highly correlated with tumor progression. On the other hand, NF kappaB directly regulated the transcription of miR-130b by binding with its promoter region. Importantly, we verify that, through deceasing the expression of Cylindromatosis (CYLD), a K63-specific DUB and endogenous blocker of NF-kappaB signaling, miR-130b can in return sustain the persistent activation of NF-kappaB, which may promote the malignant progression of TCC. Thus, the present study uncovers a potential signaling transduction in which NF-kappaB is continuously activated, and may provide a novel therapeutic approach for the clinical management of TCC. PMID- 27391067 TI - A dose-dependent perturbation in cardiac energy metabolism is linked to radiation induced ischemic heart disease in Mayak nuclear workers. AB - Epidemiological studies show a significant increase in ischemic heart disease (IHD) incidence associated with total external gamma-ray dose among Mayak plutonium enrichment plant workers. Our previous studies using mouse models suggest that persistent alteration of heart metabolism due to the inhibition of peroxisome proliferator-activated receptor (PPAR) alpha accompanies cardiac damage after high doses of ionising radiation. The aim of the present study was to elucidate the mechanism of radiation-induced IHD in humans. The cardiac proteome response to irradiation was analysed in Mayak workers who were exposed only to external doses of gamma rays. All participants were diagnosed during their lifetime with IHD that also was the cause of death. Label-free quantitative proteomics analysis was performed on tissue samples from the cardiac left ventricles of individuals stratified into four radiation dose groups (0 Gy, < 100 mGy, 100-500 mGy, and > 500 mGy). The groups could be separated using principal component analysis based on all proteomics features. Proteome profiling showed a dose-dependent increase in the number of downregulated mitochondrial and structural proteins. Both proteomics and immunoblotting showed decreased expression of several oxidative stress responsive proteins in the irradiated hearts. The phosphorylation of transcription factor PPAR alpha was increased in a dose-dependent manner, which is indicative of a reduction in transcriptional activity with increased radiation dose. These data suggest that chronic external radiation enhances the risk for IHD by inhibiting PPAR alpha and altering the expression of mitochondrial, structural, and antioxidant components of the heart. PMID- 27391068 TI - Loss of LSR affects epithelial barrier integrity and tumor xenograft growth of CaCo-2 cells. AB - The lipolysis-stimulated lipoprotein receptor (LSR) is a lipoprotein receptor, serves as host receptor for clostridial iota-like toxins and is involved in the formation of tricellular contacts. Of particular interest is the role of LSR in progression of various cancers. Here we aimed to study the tumor growth of LSR deficient colon carcinoma-derived cell lines HCT116 and CaCo-2 in a mouse xenograft model. Whereas knockout of LSR had no effect on tumor growth of HCT116 cells, we observed that CaCo-2 LSR knockout tumors grew to a smaller size than their wild-type counterparts. Histological analysis revealed increased apoptotic and necrotic cell death in a tumor originating from LSR-deficient CaCo-2 cells. LSR-deficient CaCo-2 cells exhibited increased cell proliferation in vitro and an altered epithelial morphology with impaired targeting of tricellulin to tricellular contacts. In addition, loss of LSR reduced the transepithelial electrical resistance of CaCo-2 cell monolayers and increased permeability for small molecules. Moreover, LSR-deficient CaCo-2 cells formed larger cysts in 3D culture than their wild-type counterparts. Our study provides evidence that LSR affects epithelial morphology and barrier formation in CaCo-2 cells and examines for the first time the effects of LSR deficiency on the tumor growth properties of colon carcinoma-derived cell lines. PMID- 27391069 TI - P2X7 targeting inhibits growth of human mesothelioma. AB - Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2X7 (P2RX7 or P2X7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation. In this report we show that the P2X7R is expressed by three MPM cell lines established from MPM patients but not by mesothelial cells from healthy subjects (healthy mesothelial cells, HMCs). MPM cell proliferation was inhibited by in vitro incubation in the presence of selective P2X7R antagonists, as well as by stimulation with the P2X7R agonist BzATP. Systemic administration of the selective P2X7R blocker AZ10606120 inhibited in vivo growth of MPM tumors whether implanted subcutaneously (s.c.) or intraperitoneally (i.p.). Our findings suggest that the P2X7R might be a novel target for the therapy of mesothelioma. PMID- 27391070 TI - Integrated omics-analysis reveals Wnt-mediated NAD+ metabolic reprogramming in cancer stem-like cells. AB - Abnormal tumor cell metabolism is a consequence of alterations in signaling pathways that provide critical selective advantage to cancer cells. However, a systematic characterization of the metabolic and signaling pathways altered in cancer stem-like cells (CSCs) is currently lacking. Using nuclear magnetic resonance and mass spectrometry, we profiled the whole-cell metabolites of a pair of parental (P-231) and stem-like cancer cells (S-231), and then integrated with whole transcriptome profiles. We identified elevated NAAD+ in S-231 along with a coordinated increased expression of genes in Wnt/calcium signaling pathway, reflecting the correlation between metabolic reprogramming and altered signaling pathways. The expression of CD38 and ALP, upstream NAAD+ regulatory enzymes, was oppositely regulated between P- and S-231; high CD38 strongly correlated with NAADP in P-231 while high ALP with NAAD+ levels in S-231. Antagonizing Wnt activity by dnTCF4 transfection reversed the levels of NAAD+ and ALP expression in S-231. Of note, elevated NAAD+ caused a decrease of cytosolic Ca2+ levels preventing calcium-induced apoptosis in nutrient-deprived conditions. Reprograming of NAD+ metabolic pathway instigated by Wnt signaling prevented cytosolic Ca2+ overload thereby inhibiting calcium-induced apoptosis in S-231. These results suggest that "oncometabolites" resulting from cross talk between the deranged core cancer signaling pathway and metabolic network provide a selective advantage to CSCs. PMID- 27391071 TI - High intensity focused ultrasound inhibits melanoma cell migration and metastasis through attenuating microRNA-21-mediated PTEN suppression. AB - High intensity focused ultrasound (HIFU) technology is becoming a potential noninvasive treatment for solid tumor. To explore whether HIFU can be applied to treat melanoma and its metastasis, we investigated the effect of HIFU on murine melanoma model. While there was little influence on cell survival, viability or apoptosis, HIFU exposure suppressed melanoma cell migration in vitro and metastasis in vivo. The expression of microRNA-21(miR-21) was down-regulated and PTEN expression was up-regulated in response to HIFU exposure, which was in concomitant with the reduction of AKT activity. Furthermore, ectopic miR-21 expression suppressed this effect of HIFU. These results demonstrate that HIFU exposure can inhibit AKT-mediated melanoma metastasis via miR-21 inhibition to restore PTEN expression. Therefore, targeting the miR-21/PTEN/AKT pathway might be a novel strategy of HIFU in treatment of melanoma. PMID- 27391072 TI - Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain. AB - Although nervous and vascular systems are functionally different, they usually share similar mechanisms for function maintenance. Neurovascular dysfunction has became the pathogenesis of several vascular and nervous disorders. Here we show that long non-coding RNA-MIAT is aberrantly expressed under neurovascular dysfunction condition. MIAT is shown as a regulator of vascular dysfunction, including retinal angiogenesis, corneal angiogenesis, and vascular permeability. MIAT is also shown as a regulator of retinal neurodegeneration under diabetic condition. Mechanistically, MIAT regulates neural and vascular cell function via MIAT/miR-150-5p/VEGF network. The eye is a valuable model to study central nervous system (CNS) disorders. We show that MIAT knockdown leads to cerebral microvascular degeneration, progressive neuronal loss and neurodegeneration, and behavioral deficits in a CNS neurovascular disorder, Alzheimer's disease. MIAT may represent a pharmacological target for treating neurovascular-related disorders. PMID- 27391073 TI - Dasatinib-loaded albumin nanoparticles possess diminished endothelial cell barrier disruption and retain potent anti-leukemia cell activity. AB - Dasatinib (DAS), a second-generation tyrosine kinase inhibitor, is highly effective in treating chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. However, its clinical use is limited due to serious adverse effects. DAS can disrupt endothelial barrier integrity and increase endothelial permeability which may cause peripheral edema and pleural effusion. Albumin nanoparticles (NPs) as a drug carrier may serve as a useful tool for cell-selective drug delivery to reduce DAS-induced endothelial hyperpermeability and maintain endothelial barrier integrity. In this study, we reported that DAS-loaded NPs exhibited potent anti-leukemia efficacy as DAS alone. Importantly, albumin NPs as a drug carrier markedly reduced DAS-induced endothelial hyperpermeability by restraining the inhibition of Lyn kinase signaling pathway in endothelial cells. Therefore, albumin NPs could be a potential tool to improve anti-leukemia efficacy of DAS through its cell selective effects. PMID- 27391074 TI - Novel ERalpha positive breast cancer model with estrogen independent growth in the bone microenvironment. AB - Despite successful therapeutic options for estrogen receptor-alpha (ERalpha)+ breast cancer, resistance to endocrine therapy frequently occurs leading to tumor recurrence. In addition to intrinsic changes in the cancer cells, herein we demonstrate that tumor cell-microenvironment interactions can drive recurrence at specific sites. By using two ERalpha+ cell lines derived from spontaneous mammary carcinomas in STAT1-/- mice (SSM2, SSM3), we establish that the bone microenvironment offers growth advantage over primary site or lung in the absence of ovarian hormones. While SSM3 did not engraft at primary and skeletal locations in the absence of estrogen, SSM2 selectively grew in bone of ovariectomized mice and following administration of aromatase inhibitors. However, SSM2 growth remained hormone-dependent at extraskeletal sites. Unexpectedly, bone-residing SSM2 cells retained ERalpha expression and JAK2/STAT3 activation regardless of the hormonal status. These data position the bone microenvironment as a unique site for acquisition of tumor/estrogen independency and identify the first ERalpha+ hormone-independent tumor model in immunocompetent mice. PMID- 27391075 TI - Organophosphate ester flame retardant concentrations and distributions in serum from inhabitants of Shandong, China, and changes between 2011 and 2015. AB - The production and use of brominated flame retardants have been increasingly restricted. Organophosphate esters (OPEs) have been widely used as substitutes for brominated flame retardants. However, little is yet known about human exposure to OPEs. The potential health risks posed by OPEs were assessed by determining the concentrations of 6 OPEs in pooled serum samples from residents of Shandong, China. The mean ?6 OPE concentrations in 2011 and 2015 were 680 ng/g lipid and 709 ng/g lipid, respectively. The most abundant OPE was tri(2 chloroethyl) phosphate, contributing a mean of 82% of the ?6 OPE concentration. A significant correlation was found between the tri(2-chloroethyl) phosphate and tri-n-butylphosphate concentrations, possibly indicating that these OPEs are used in similar applications and have similar human exposure pathways in the study area. The mean tri(2-chloroethyl) phosphate concentration increased from 536 ng/g lipid in 2011 to 605 ng/g lipid in 2015, but the concentrations of tri-n butylphosphate, triphenyl phosphate, and tris(methylphenyl) esters decreased between 2011 and 2015. This could indicate that chlorinated OPEs bioaccumulate in humans more strongly than nonchlorinated OPEs do. Environ Toxicol Chem 2017;36:414-421. (c) 2016 SETAC. PMID- 27391076 TI - Illumina Sequencing Reveals Aberrant Expression of MicroRNAs and Their Variants in Whitefish (Coregonus lavaretus) Liver after Exposure to Microcystin-LR. AB - Molecular analyses show that challenging fish with microcystin-LR (MC-LR) causes perturbations of microRNA (miRNA) signaling. However, the significance and scope of these alterations is currently unknown. To address this issue, we studied miRNA gene expression in the liver of juvenile whitefish, C. lavaretus, during 28 days of exposure to a subacute dose of MC-LR (100 MUg.kg-1 body mass). Using genomic resources of Atlantic salmon (AGKD03), the mature miRNA library of Atlantic salmon (miRBase-21) and bioinformatics tools (sRNAbench), we discovered and annotated a total of 377 distinct mature miRNAs belonging to 93 families of evolutionary conserved miRNAs, as well as 24 novel mature miRNA candidates that were mapped to 14 distinct S. salar miRNA precursors. miRNA-Seq transcriptome profiling of liver tissues revealed differential miRNA expression in control and treated fish at 14 days (73 miRNAs were modulated) and at 28 days (83 miRNAs) of the treatment, subsequently validated by qPCR for nine selected differentially expressed miRNAs. Additional qPCR study confirmed the miRNA-Seq data and revealed consistent, aberrant miRNAs expression profile in the later phase of MC-LR hepatotoxicity (7-28 d). Functional annotation analysis revealed that the aberrantly expressed miRNAs have target genes involved in cytoskeletal remodeling, cell metabolism, cell cycle regulation and apoptosis; dysregulation of these processes in liver cells leads to cirrhosis and hepatocellular carcinoma in humans. To enable deeper insight into the molecular responses of liver cells in fish exposed to MC-LR, we expanded the miRNAome analysis by inclusion of miRNA variants (isomiRs) profiles, and we showed that the isomiR profiles of liver specific MiR122, and a few other miRNAs, correlated with MC-LR treatment. Given the importance of isomiRs for disease biology in mammals, we believe that further research focused on the miRNA isoforms will bring us closer to better understanding the molecular mechanisms of MC-LR hepatotoxicity. PMID- 27391077 TI - The Outcome of Breast Cancer Is Associated with National Human Development Index and Health System Attainment. AB - Breast cancer is a worldwide threat to female health with patient outcomes varying widely. The exact correlation between global outcomes of breast cancer and the national socioeconomic status is still undetermined. Mortality-to incidence ratio (MIR) of breast cancer was calculated with the contemporary age standardized incidence and mortality rates for countries with data available at GLOBOCAN 2012 database. The MIR matched national human development indexes (HDIs) and health system attainments were respectively obtained from Human Development Report and World Health Report. Correlation analysis, regression analysis, and Tukey-Kramer post hoc test were used to explore the effects of HDI and health system attainment on breast cancer MIR. Our results demonstrated that breast cancer MIR was inversely correlated with national HDI (r = -.950; P < .001) and health system attainment (r = -.898; P < .001). Countries with very high HDI had significantly lower MIRs than those with high, medium and low HDI (P < .001). Liner regression model by ordinary least squares also indicated negative effects of both HDI (adjusted R2 = .903, standardize beta = -.699, P < .001) and health system attainment (adjusted R2 =. 805, standardized beta = -.009; P < .001), with greater effects in developing countries identified by quantile regression analysis. It is noteworthy that significant health care disparities exist among countries in accordance with the discrepancy of HDI. Policies should be made in less developed countries, which are more likely to obtain worse outcomes in female breast cancer, that in order to improve their comprehensive economic strength and optimize their health system performance. PMID- 27391079 TI - Leaf vein fraction influences the Peclet effect and 18 O enrichment in leaf water. AB - The process of evaporation results in the fractionation of water isotopes such that the lighter 16 O isotope preferentially escapes the gas phase leaving the heavier 18 O isotope to accumulate at the sites of evaporation. This applies to transpiration from a leaf with the degree of fractionation dependent on a number of environmental and physiological factors that are well understood. Nevertheless, the 18 O enrichment of bulk leaf water is often less than that predicted for the sites of evaporation. The advection of less enriched water in the transpiration stream has been suggested to limit the back diffusion of enriched evaporative site water (Peclet effect); however, evidence for this effect has been varied. In sampling across a range of species with different vein densities and saturated water contents, we demonstrate the importance of accounting for the relative 'pool' sizes of the vascular and mesophyll water for the interpretation of a Peclet effect. Further, we provide strong evidence for a Peclet signal within the xylem that if unaccounted for can lead to confounding of the estimated enrichment within the mesophyll water. This has important implications for understanding variation in the effective path length of the mesophyll and hence potentially the delta18 O of organic matter. PMID- 27391078 TI - Mesenchymal Stem Cells (MSC) Regulate Activation of Granulocyte-Like Myeloid Derived Suppressor Cells (G-MDSC) in Chronic Myeloid Leukemia Patients. AB - It is well known that mesenchymal stem cells (MSC) have a role in promotion of tumor growth, survival and drug-resistance in chronic myeloid leukemia (CML). Recent reports indicated that a subpopulation of myeloid cells, defined as granulocyte-like myeloid-derived suppressor cells (G-MDSC) is increased in these patients. So far, the role of MSC in MDSC expansion and activation into the BM microenvironment remains unexplored. To address this question, here we use a specific experimental model in vitro, co-culturing MSC with peripheral blood mononucleated cells (PBMC) from normal individuals, in order to generate MSC educated G-MDSC. Although MSC of healthy donors (HD) and CML patients were able to generate the same amount of MDSC, only CML-MSC-educated G-MDSC exhibited suppressive ability on autologous T lymphocytes. In addition, compared with HD MSC, CML-MSC over-expressed some immunomodulatory factors including TGFbeta, IL6 and IL10, that could be involved in MDSC activation. CML-MSC-educated G-MDSC expressed higher levels of ARG1, TNFalpha, IL1beta, COX2 and IL6 than G-MDSC isolated from co-culture with HD-MSC. Our data provide evidence that CML-MSC may play a critical role in tumor microenvironment by orchestrating G-MDSC activation and regulating T lymphocytes-mediated leukemia surveillance, thus contributing to CML immune escape. PMID- 27391080 TI - FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling. AB - Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types; however, its roles in osteoblast lineage cells are largely unknown. We show herein that mice lacking FAK in Osterix expressing cells exhibited decreased osteoblast number and low bone mass as well as increased bone marrow adiposity. The decreased bone mass in FAK-deficient mice was accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow Osterix expressing cells resulting from downregulation of Wnt/beta-catenin signaling due to the reduced expression of canonical Wnt ligands. In contrast, FAK loss in calvarial preosteoblasts had no adverse effect on their proliferation and osteogenic differentiation and these cells had intact Wnt/beta-catenin signaling. (c) 2016 American Society for Bone and Mineral Research. PMID- 27391081 TI - AvrRxo1 Is a Bifunctional Type III Secreted Effector and Toxin-Antitoxin System Component with Homologs in Diverse Environmental Contexts. AB - Toxin-antitoxin (TA) systems are ubiquitous bacterial systems that may function in genome maintenance and metabolic stress management, but are also thought to play a role in virulence by helping pathogens survive stress. We previously demonstrated that the Xanthomonas oryzae pv. oryzicola protein AvrRxo1 is a type III-secreted virulence factor that has structural similarities to the zeta family of TA toxins, and is toxic to plants and bacteria in the absence of its predicted chaperone Arc1. In this work, we confirm that AvrRxo1 and its binding partner Arc1 function as a TA system when expressed in Escherichia coli. Sequences of avrRxo1 homologs were culled from published and newly generated phytopathogen genomes, revealing that avrRxo1:arc1 modules are rare or frequently inactivated in some species and highly conserved in others. Cloning and functional analysis of avrRxo1 from Acidovorax avenae, A. citrulli, Burkholderia andropogonis, Xanthomonas translucens, and Xanthomonas euvesicatoria showed that some AvrRxo1 homologs share the bacteriostatic and Rxo1-mediated cell death triggering activities of AvrRxo1 from X. oryzae. Additional distant putative homologs of avrRxo1 and arc1 were identified in genomic or metagenomic sequence of environmental bacteria with no known pathogenic role. One of these distant homologs was cloned from the filamentous soil bacterium Cystobacter fuscus. avrRxo1 from C. fuscus caused watersoaking and triggered Rxo1-dependent cell collapse in Nicotiana benthamiana, but no growth suppression in E. coli was observed. This work confirms that a type III effector can function as a TA system toxin, and illustrates the potential of microbiome data to reveal new environmental origins or reservoirs of pathogen virulence factors. PMID- 27391083 TI - Pain networks from the inside: Spatiotemporal analysis of brain responses leading from nociception to conscious perception. AB - Conscious perception of painful stimuli needs the contribution of an extensive cortico-subcortical network, and is completed in less than one second. While initial activities in operculo-insular and mid-cingulate cortices have been extensively assessed, the activation timing of most areas supporting conscious pain has barely been studied. Here we used intracranial EEG to investigate the dynamics of 16 brain regions (insular, parietal, prefrontal, cingulate, hippocampal and limbic) during the first second following nociceptive-specific laser pulses. Three waves of activation could be defined according to their temporal relation with conscious perception, ascertained by voluntary motor responses. Pre-conscious activities were recorded in the posterior insula, operculum, mid-cingulate and amygdala. Antero-insular, prefrontal and posterior parietal activities started later and developed during time-frames consistent with conscious voluntary reactions. Responses from hippocampus, perigenual and perisplenial cingulate developed latest and persisted well after conscious perception occurred. Nociceptive inputs reach simultaneously sensory and limbic networks, probably through parallel spino-thalamic and spino-parabrachial pathways, and the initial limbic activation precedes conscious perception of pain. Access of sensory information to consciousness develops concomitant to fronto-parietal activity, while late-occurring responses in the hippocampal region, perigenual and posterior cingulate cortices likely underlie processes linked to memory encoding, self-awareness and pain modulation. Hum Brain Mapp 37:4301-4315, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27391082 TI - The Instrumented Sit-to-Stand Test (iSTS) Has Greater Clinical Relevance than the Manually Recorded Sit-to-Stand Test in Older Adults. AB - BACKGROUND: The ability to rise from sitting to standing is critical to an individual's quality of life, as it is a prerequisite for functional independence. The purpose of the current study was to examine the hypothesis that test durations as assessed with the instrumented repeated Sit-To-Stand (STS) show stronger associations with health status, functional status and daily physical activity of older adults than manually recorded test durations. METHODS: In 63 older participants (mean age 83 +/-6.9 years, 51 female), health status was assessed using the European Quality of Life questionnaire and functional status was assessed using the physical function index of the of the RAND-36. Physical performance was measured using a wearable sensor-based STS test. From this test, durations, sub-durations and kinematics of the STS movements were estimated and analysed. In addition, physical activity was measured for one week using an activity monitor and episodes of lying, sitting, standing and locomotion were identified. Associations between STS parameters with health status, functional status and daily physical activity were assessed. RESULTS: The manually recorded STS times were not significantly associated with health status (p = 0.457) and functional status (p = 0.055), whereas the instrumented STS times were (both p = 0.009). The manually recorded STS durations showed a significant association to daily physical activity for mean sitting durations (p = 0.042), but not for mean standing durations (p = 0.230) and mean number of locomotion periods (p = 0.218). Furthermore, durations of the dynamic sit-to-stand phase of the instrumented STS showed more significant associations with health status, functional status and daily physical activity (all p = 0.001) than the static phases standing and sitting (p = 0.043-0.422). CONCLUSIONS: As hypothesized, instrumented STS durations were more strongly associated with participant health status, functional status and physical activity than manually recorded STS durations in older adults. Furthermore, instrumented STS allowed assessment of the dynamic phases of the test, which were likely more informative than the static sitting and standing phases. PMID- 27391084 TI - Tree Morphologic Plasticity Explains Deviation from Metabolic Scaling Theory in Semi-Arid Conifer Forests, Southwestern USA. AB - A significant concern about Metabolic Scaling Theory (MST) in real forests relates to consistent differences between the values of power law scaling exponents of tree primary size measures used to estimate mass and those predicted by MST. Here we consider why observed scaling exponents for diameter and height relationships deviate from MST predictions across three semi-arid conifer forests in relation to: (1) tree condition and physical form, (2) the level of inter-tree competition (e.g. open vs closed stand structure), (3) increasing tree age, and (4) differences in site productivity. Scaling exponent values derived from non linear least-squares regression for trees in excellent condition (n = 381) were above the MST prediction at the 95% confidence level, while the exponent for trees in good condition were no different than MST (n = 926). Trees that were in fair or poor condition, characterized as diseased, leaning, or sparsely crowned had exponent values below MST predictions (n = 2,058), as did recently dead standing trees (n = 375). Exponent value of the mean-tree model that disregarded tree condition (n = 3,740) was consistent with other studies that reject MST scaling. Ostensibly, as stand density and competition increase trees exhibited greater morphological plasticity whereby the majority had characteristically fair or poor growth forms. Fitting by least-squares regression biases the mean-tree model scaling exponent toward values that are below MST idealized predictions. For 368 trees from Arizona with known establishment dates, increasing age had no significant impact on expected scaling. We further suggest height to diameter ratios below MST relate to vertical truncation caused by limitation in plant water availability. Even with environmentally imposed height limitation, proportionality between height and diameter scaling exponents were consistent with the predictions of MST. PMID- 27391085 TI - Complexity, Training Paradigm Design, and the Contribution of Memory Subsystems to Grammar Learning. AB - Although there is variability in nonnative grammar learning outcomes, the contributions of training paradigm design and memory subsystems are not well understood. To examine this, we presented learners with an artificial grammar that formed words via simple and complex morphophonological rules. Across three experiments, we manipulated training paradigm design and measured subjects' declarative, procedural, and working memory subsystems. Experiment 1 demonstrated that passive, exposure-based training boosted learning of both simple and complex grammatical rules, relative to no training. Additionally, procedural memory correlated with simple rule learning, whereas declarative memory correlated with complex rule learning. Experiment 2 showed that presenting corrective feedback during the test phase did not improve learning. Experiment 3 revealed that structuring the order of training so that subjects are first exposed to the simple rule and then the complex improved learning. The cumulative findings shed light on the contributions of grammatical complexity, training paradigm design, and domain-general memory subsystems in determining grammar learning success. PMID- 27391086 TI - Kinetics of Linezolid in Continuous Renal Replacement Therapy: An In Vitro Study. AB - BACKGROUND: Continuous veno-venous hemofiltration (CVVH) could affect the pharmacokinetic profile of linezolid (LZD). The aim of this study was to evaluate the LZD extracorporeal clearance using an in vitro CVVH model. METHODS: A sham miniaturized CVVH circuit (CARPEDIEM; Bellco, Mirandola, Italy) was set up with a polysulfone hemofilter (0.25 m; cutoff 50,000 Da) for 240 minutes using normal saline solution (0.9% wt/vol NaCl) and blood (n = 6) spiked with LZD. Drug solution samples were collected during CVVH at 10, 30, 60, 120, and 240 minutes. LZD levels were measured by high-performance liquid chromatography. RESULTS: Results were used to estimate pharmacokinetic parameters. The LZD baseline level decreased from 17.24 +/- 0.54 to 9.73 +/- 4.85 mg/L and from 11.75 +/- 0.08 to 5.01 +/- 0.67 mg/L in the first 10 minutes, and then increased to 13.2 +/- 3.10 and 7.4 +/- 0.71 mg/L in normal saline solution and blood, respectively. Mass balance analysis reported a rapid adsorption of LZD onto a polysulfone membrane followed by its release: a rebound phenomenon occurred. CONCLUSIONS: Although further studies are necessary to clarify this phenomenon, LZD level variations observed in our study should be considered to avoid antimicrobial underexposure. Several strategies are available for adjusting the dosage regimen of LZD, but therapeutic drug monitoring is highly recommended when it is used. PMID- 27391087 TI - Aggression and Violence: Perennial Concerns for Psychiatric-Mental Health Nursing. PMID- 27391088 TI - Engineering Surface Energy and Nanostructure of Microporous Films for Expanded Membrane Distillation Applications. AB - We investigated the factors that determine surface omniphobicity of microporous membranes and evaluated the potential application of these membranes in desalination of low surface tension wastewaters by membrane distillation (MD). Specifically, the effects of surface morphology and surface energy on membrane surface omniphobicity were systematically investigated by evaluating wetting resistance to low surface tension liquids. Single and multilevel re-entrant structures were achieved by using cylindrical glass fibers as a membrane substrate and grafting silica nanoparticles (SiNPs) on the fibers. Surface energy of the membrane was tuned by functionalizing the fiber substrate with fluoroalkylsilane (FAS) having two different lengths of fluoroalkyl chains. Results show that surface omniphobicity of the modified fibrous membrane increased with higher level of re-entrant structure and with lower surface energy. The secondary re-entrant structure achieved by SiNP coating on the cylindrical fibers was found to play a critical role in enhancing the surface omniphobicity. Membranes coated with SiNPs and chemically modified by the FAS with a longer fluoroalkyl chain (or lower surface energy) exhibited excellent surface omniphobicity and showed wetting resistance to low surface tension liquids such as ethanol (22.1 mN m(-1)). We further evaluated performance of the membranes in desalination of saline feed solutions with varying surface tensions by membrane distillation (MD). The engineered membranes exhibited stable MD performance with low surface tension feed waters, demonstrating the potential application omniphobic membranes in desalinating complex, high salinity industrial wastewaters. PMID- 27391089 TI - Transforming mental health services to address gender disparities in depression risk factors. AB - Depression in older women is a significant and growing problem. Women who experience life stressors across the life span are at higher risk for developing depression than their male counterparts. Research has focused primarily on identifying and reducing the symptoms of depression for the general aging population, disregarding gender-specific differences in the foundational causes of depression. This article examines how women's unique experiences influence the development of depression and highlights how the current mental health system could better meet older women's needs by moving from a gender-neutral model to one that emphasizes women's experiences. PMID- 27391091 TI - In Memoriam-Hank Edelhauser (1937-2015). PMID- 27391090 TI - Preferentially Expressed Antigen of Melanoma Prevents Lung Cancer Metastasis. AB - Lung cancer is the most common cause of cancer death worldwide. The poor survival rate is largely due to the extensive local invasion and metastasis. However, the mechanisms underlying the invasion and metastasis of lung cancer cells remain largely elusive. In this study, we examined the role of preferentially expressed antigen of melanoma (PRAME) in lung cancer metastasis. Our results show that PRAME is downregulated in lung adenocarcinoma and lung bone metastasis compared with normal human lung. Knockdown of PRAME decreases the expression of E-Cadherin and promotes the proliferation, invasion, and metastasis of lung cancer cells by regulating multiple critical genes, most of which are related to cell migration, including MMP1, CCL2, CTGF, and PLAU. Clinical data analysis reveals that the expression of MMP1 correlates with the clinical features and outcome of lung adenocarcinoma. Taken together, our data demonstrate that PRAME plays a role in preventing the invasion and metastasis of lung adenocarcinoma and novel diagnostic or therapeutic strategies can be developed by targeting PRAME. PMID- 27391092 TI - Incidence, Risk Factors, and Surgical Management of Boston Type 1 Keratoprothesis Corneal Melts, Leaks, and Extrusions. AB - PURPOSE: To determine the rate of Boston type 1 keratoprosthesis (Kpro)-related corneal melts, leaks, and extrusions requiring surgical repair and to analyze possible risk factors and visual outcomes. METHODS: Retrospective chart review of 110 patients (128 eyes) who received a Kpro between November 2004 and December 2010 (average follow-up of 29 mo). The rate of corneal complications, risk factors for melts, and postmelt repair visual outcomes were evaluated. RESULTS: Twenty eyes from 18 patients developed Kpro-related melts requiring surgical repair. The incidence of melt-related complications was 16%. In total, there were 33 episodes of melt-related complications. Surgical repair included lamellar patch grafts (15), Kpro removal with penetrating keratoplasty (7), reassembly of Kpro onto a new cornea (4), replacement of Kpro (3), suturing of a leak (3), and enucleation (1). The majority of eyes (18/20) did not regain their best post-Kpro vision at final follow-up (average 10 mo and range, 1-36 mo after melt repair). Significant risk factors for melt included previous infectious keratitis [P < 0.0001, odds ratio (OR) = 12.50, 95% confidence interval (CI), 4.02-38.9] and conjunctival deficiency (ie, a diagnosis of Stevens-Johnson syndrome, mucous membrane pemphigoid, or chemical injury, P = 0.043, OR = 2.66, CI, 1.01-7.02). CONCLUSIONS: Patients who undergo Kpro with severe ocular surface disease are at greater risk for corneal melts, leaks, and extrusions. Patients with infectious keratitis and conjunctival deficiency are at an increased risk of developing corneal melts. Visual outcomes are poor after surgical repair of these complications. PMID- 27391093 TI - Characterization of Goblet Cells in a Pterygium Biopsy Using Laser Scanning Confocal Microscopy and Immunohistochemistry. AB - PURPOSE: To confirm that structures presumed to be GCs observed using laser scanning confocal microscopy (LSCM) are actually GCs. METHODS: A single tissue sample was obtained from a pterygium that was freshly excised from a 33-year-old male. After viewing what were believed to be GCs in the tissue sample using LSCM, the same sample was observed using laboratory confocal microscopy and immunohistochemistry. GCs were identified by a combination of classic morphologic appearance and the use of immunofluorescence to antibodies for mucin 5AC and cytokeratin-7. The LSCM and immunohistochemistry results were compared. RESULTS: Using LSCM, GCs were observed between 7 and 41 MUm deep, at the level of the superficial basal cells of the tissue sample. GCs were estimated to have a diameter of 35-40 MUm near the surface and 20-30 MUm in the deeper layers. A small dark dot was visible in some GCs, indicating cell nuclei and/or the opened apical portion of cells representing the site of mucin release. GCs were more reflective and larger than the surrounding cells. Positively stained GCs in immunofluorescence showed a similar distribution pattern to those observed with LSCM. The tissue sample stained intensely for GC-specific mucin type 5AC. CONCLUSIONS: The pattern of discrete, large reflective cells observed using LSCM are likely to be GCs. PMID- 27391095 TI - Synthesis of Semiconductor Nanocrystals, Focusing on Nontoxic and Earth-Abundant Materials. AB - We review the synthesis of semiconductor nanocrystals/colloidal quantum dots in organic solvents with special emphasis on earth-abundant and toxic heavy metal free compounds. Following the Introduction, section 2 defines the terms related to the toxicity of nanocrystals and gives a comprehensive overview on toxicity studies concerning all types of quantum dots. Section 3 aims at providing the reader with the basic concepts of nanocrystal synthesis. It starts with the concepts currently used to describe the nucleation and growth of monodisperse particles and next takes a closer look at the chemistry of the inorganic core and its interactions with surface ligands. Section 4 reviews in more detail the synthesis of different families of semiconductor nanocrystals, namely elemental group IV compounds (carbon nanodots, Si, Ge), III-V compounds (e.g., InP, InAs), and binary and multinary metal chalcogenides. Finally, the authors' view on the perspectives in this field is given. PMID- 27391096 TI - Correction: Harvest Pressure on Coastal Atlantic Cod (Gadus morhua) from Recreational Fishing Relative to Commercial Fishing Assessed from Tag-Recovery Data. AB - [This corrects the article DOI: 10.1371/journal.pone.0149595.]. PMID- 27391094 TI - How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact. AB - BACKGROUND: Randomized controlled trials reported that pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance. METHODS: We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations. RESULTS: Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days) in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug resistant HIV (25%-90%); and the likelihood of resistance acquisition upon transmission (10%-75%). These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence. CONCLUSIONS: There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become infected despite the use of PrEP should be closely monitored due to higher risk of virological failure when initiating antiretroviral treatment in the future. PMID- 27391097 TI - Excellent outcome of hairy cell leukaemia with extensive mesenteric infiltration following cladribine therapy. PMID- 27391098 TI - Vaccination Confidence and Parental Refusal/Delay of Early Childhood Vaccines. AB - OBJECTIVE: To support efforts to address parental hesitancy towards early childhood vaccination, we sought to validate the Vaccination Confidence Scale using data from a large, population-based sample of U.S. parents. METHODS: We used weighted data from 9,354 parents who completed the 2011 National Immunization Survey. Parents reported on the immunization history of a 19- to 35 month-old child in their households. Healthcare providers then verified children's vaccination status for vaccines including measles, mumps, and rubella (MMR), varicella, and seasonal flu. We used separate multivariable logistic regression models to assess associations between parents' mean scores on the 8 item Vaccination Confidence Scale and vaccine refusal, vaccine delay, and vaccination status. RESULTS: A substantial minority of parents reported a history of vaccine refusal (15%) or delay (27%). Vaccination confidence was negatively associated with refusal of any vaccine (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.54-0.63) as well as refusal of MMR, varicella, and flu vaccines specifically. Negative associations between vaccination confidence and measures of vaccine delay were more moderate, including delay of any vaccine (OR = 0.81, 95% CI, 0.76-0.86). Vaccination confidence was positively associated with having received vaccines, including MMR (OR = 1.53, 95% CI, 1.40-1.68), varicella (OR = 1.54, 95% CI, 1.42-1.66), and flu vaccines (OR = 1.32, 95% CI, 1.23-1.42). CONCLUSIONS: Vaccination confidence was consistently associated with early childhood vaccination behavior across multiple vaccine types. Our findings support expanding the application of the Vaccination Confidence Scale to measure vaccination beliefs among parents of young children. PMID- 27391099 TI - Fluorinated Peptide Nucleic Acids with Fluoroacetyl Side Chain Bearing 5-(F/CF3) Uracil: Synthesis and Cell Uptake Studies. AB - Fluorine incorporation into organic molecules imparts favorable physicochemical properties such as lipophilicity, solubility and metabolic stability necessary for drug action. Toward such applications using peptide nucleic acids (PNA), we herein report the chemical synthesis of fluorinated PNA monomers and biophysical studies of derived PNA oligomers containing fluorine in in the acetyl side chain (-CHF-CO-) bearing nucleobase uracil (5-F/5-CF3-U). The crystal structures of fluorinated racemic PNA monomers reveal interesting base pairing of enantiomers and packing arrangements directed by the chiral F substituent. Reverse phase HPLC show higher hydrophobicity of fluorinated PNA oligomers, dependent on the number and site of the fluorine substitution: fluorine on carbon adjacent to the carbonyl group induces higher lipophilicity than fluorine on nucleobase or in the backbone. The PNA oligomers containing fluorinated bases form hybrids with cDNA/RNA with slightly lower stability compared to that of unmodified aeg PNA, perhaps due to electronic effects. The uptake of fluorinated homooligomeric PNAs by HeLa cells was as facile as that of nonfluorinated PNA. In conjunction with our previous work on PNAs fluorinated in backbone and at N-terminus, it is evident that the fluorinated PNAs have potential to emerge as a new class of PNA analogues for applications in functional inhibition of RNA. PMID- 27391100 TI - Determination of Personalized IOL-Constants for the Haigis Formula under Consideration of Measurement Precision. AB - The capabilities of a weighted least squares approach for the optimization of the intraocular lens (IOL) constants for the Haigis formula are studied in comparison to an ordinary least squares approach. The weights are set to the inverse variances of the effective optical anterior chamber depth. The effect of random measurement noise is simulated 100000 times using data from N = 69 cataract patients and the measurement uncertainty of two different biometers. A second, independent data set (N = 33) is used to show the differences that can be expected between both methods. The weighted least squares formalism reduces the effect of measurement error on the final constants. In more than 64% it will result in a better approximation, if the measurement errors are estimated correctly. The IOL constants can be calculated with higher precision using the weighted least squares method. PMID- 27391101 TI - Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice. AB - BACKGROUND: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. METHODS: We present a new mouse model (Df(h22q11)/+) of the deletion syndrome (22q11.2DS) and report on, to our knowledge, the most comprehensive study undertaken to date in 22q11.2DS models. The study was conducted in male mice. RESULTS: We found elevated postpubertal N-methyl-D aspartate (NMDA) receptor antagonist-induced hyperlocomotion, age-independent prepulse inhibition (PPI) deficits and increased acoustic startle response (ASR). The PPI deficit and increased ASR were resistant to antipsychotic treatment. The PPI deficit was not a consequence of impaired hearing measured by auditory brain stem responses. The Df(h22q11)/+ mice also displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal elevations of the dopamine metabolite DOPAC and increased dorsal striatal expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice in a wide range of other behavioural and biochemical assays. LIMITATIONS: The 22q11.2 microdeletion has incomplete penetrance in humans, and the severity of disease depends on the complete genetic makeup in concert with environmental factors. In order to obtain more marked phenotypes reflecting the severe conditions related to 22q11.2DS it is suggested to expose the Df(h22q11)/+ mice to environmental stressors that may unmask latent psychopathology. CONCLUSION: The Df(h22q11)/+ model will be a valuable tool for increasing our understanding of the etiology of schizophrenia and other psychiatric disorders associated with the 22q11DS. PMID- 27391102 TI - Identification of Novel and Recurrent Disease-Causing Mutations in Retinal Dystrophies Using Whole Exome Sequencing (WES): Benefits and Limitations. AB - Inherited retinal dystrophies (IRDs) are Mendelian diseases with tremendous genetic and phenotypic heterogeneity. Identification of the underlying genetic basis of these dystrophies is therefore challenging. In this study we employed whole exome sequencing (WES) in 11 families with IRDs and identified disease causing variants in 8 of them. Sequence analysis of about 250 IRD-associated genes revealed 3 previously reported disease-associated variants in RHO, BEST1 and RP1. We further identified 5 novel pathogenic variants in RPGRIP1 (p.Ser964Profs*37), PRPF8 (p.Tyr2334Leufs*51), CDHR1 (p.Pro133Arg and c.439 17G>A) and PRPF31 (p.Glu183_Met193dup). In addition to confirming the power of WES in genetic diagnosis of IRDs, we document challenges in data analysis and show cases where the underlying genetic causes of IRDs were missed by WES and required additional techniques. For example, the mutation c.439-17G>A in CDHR1 would be rated unlikely applying the standard WES analysis. Only transcript analysis in patient fibroblasts confirmed the pathogenic nature of this variant that affected splicing of CDHR1 by activating a cryptic splice-acceptor site. In another example, a 33-base pair duplication in PRPF31 missed by WES could be identified only via targeted analysis by Sanger sequencing. We discuss the advantages and challenges of using WES to identify mutations in heterogeneous diseases like IRDs. PMID- 27391103 TI - Hydrological regulation drives regime shifts: evidence from paleolimnology and ecosystem modeling of a large shallow Chinese lake. AB - Quantitative evidence of sudden shifts in ecological structure and function in large shallow lakes is rare, even though they provide essential benefits to society. Such 'regime shifts' can be driven by human activities which degrade ecological stability including water level control (WLC) and nutrient loading. Interactions between WLC and nutrient loading on the long-term dynamics of shallow lake ecosystems are, however, often overlooked and largely underestimated, which has hampered the effectiveness of lake management. Here, we focus on a large shallow lake (Lake Chaohu) located in one of the most densely populated areas in China, the lower Yangtze River floodplain, which has undergone both WLC and increasing nutrient loading over the last several decades. We applied a novel methodology that combines consistent evidence from both paleolimnological records and ecosystem modeling to overcome the hurdle of data insufficiency and to unravel the drivers and underlying mechanisms in ecosystem dynamics. We identified the occurrence of two regime shifts: one in 1963, characterized by the abrupt disappearance of submerged vegetation, and another around 1980, with strong algal blooms being observed thereafter. Using model scenarios, we further disentangled the roles of WLC and nutrient loading, showing that the 1963 shift was predominantly triggered by WLC, whereas the shift ca. 1980 was attributed to aggravated nutrient loading. Our analysis also shows interactions between these two stressors. Compared to the dynamics driven by nutrient loading alone, WLC reduced the critical P loading and resulted in earlier disappearance of submerged vegetation and emergence of algal blooms by approximately 26 and 10 years, respectively. Overall, our study reveals the significant role of hydrological regulation in driving shallow lake ecosystem dynamics, and it highlights the urgency of using multi-objective management criteria that includes ecological sustainability perspectives when implementing hydrological regulation for aquatic ecosystems around the globe. PMID- 27391105 TI - Atg3 Overexpression Enhances Bortezomib-Induced Cell Death in SKM-1 Cell. AB - BACKGROUND: Myelodysplastic syndrome (MDS) is a group of heterogeneous hematopoietic stem cell malignancies with a high risk of transformation into acute myeloid leukemia (AML). Clonal evolutions are significantly associated with transformation to AML. According to a gene expression microarray, atg3 is downregulated in MDS patients progressing to leukemia, but less is known about the function of Atg3 in the survival and death of MSD/AML cells. Moreover, the role of autophagy as a result of bortezomib treatment is controversial. The current study was designed to investigate the function of Atg3 in SKM-1 cells and to study the effect of Atg3 on cell viability and cell death following bortezomib treatment. METHODS: Four leukemia cell lines (SKM-1, THP-1, NB4 and K562) and two healthy patients' bone marrow cells were analyzed for Atg3 expression via qRT-PCR and Western blotting analysis. The role of Atg3 in SKM-1 cell survival and cell death was analyzed by CCK-8 assay, trypan blue exclusion assay, DAPI staining and Annexin V/PI dual staining with or without bortezomib treatment. Western blotting analysis was used to detect proteins in autophagic and caspase signaling pathways. Electron microscopy was used to observe ultrastructural changes after Atg3 overexpression. RESULTS: Downregulation of Atg3 expression was detected in four leukemia cell lines compared with healthy bone marrow cells. Atg3 mRNA was significantly decreased in MDS patients' bone marrow cells. Overexpression of Atg3 in SKM-1 cells resulted in AKT-mTOR-dependent autophagy, a significant reduction in cell proliferation and increased cell death, which could be overcome by the autophagy inhibitor 3-MA. SKM-1 cells overexpressing Atg3 were hypersensitive to bortezomib treatment at different concentrations via autophagic cell death and enhanced sensitivity to apoptosis in the SKM-1 cell line. Following treatment with 3-MA, the sensitivity of Atg3-overexpressing cells to bortezomib treatment was reduced. Atg3 knockdown blocked cell growth inhibition and cell death induced by bortezomib. CONCLUSION: Our preliminary study of Atg3 in the high-risk MDS cell line suggests that Atg3 might be possibly a critical regulator of autophagic cell death and a gene target for therapeutic interventions in MDS. PMID- 27391107 TI - Temperature Dependent Thermal Conductivity and Thermal Interface Resistance of Pentacene Thin Films with Varying Morphology. AB - Temperature dependent thermal conductivities and thermal interface resistances of pentacene (Pn) thin films deposited on silicon substrates and self-assembled monolayer-modified [octadecyltrichlorosilane (OTS) and (3 aminopropyl)triethoxysilane (APTES)] silicon substrates were measured using frequency domain thermoreflectance. Atomic force microscopy images were used to derive an effective film thickness for thermal transport that accounts for surface roughness. Data taken over a temperature range of 77-300 K for various morphologies and film thicknesses show that the thermal conductivity increases with increasing Pn grain size. The sum of the substrate-Pn and Pn-gold thermal interface resistances was isolated from the intrinsic thermal resistance of the Pn films and found to be independent of surface chemistry. Corresponding Kapitza lengths of approximately 150 nm are larger than the physical thicknesses of typical Pn thin films and indicate that the interfaces play a dominant role in the total thermal resistance. This study has implications for increasing the performance and effective thermal management of small molecule electronic and energy conversion devices. PMID- 27391106 TI - Peptide-Recombinant VP6 Protein Based Enzyme Immunoassay for the Detection of Group A Rotaviruses in Multiple Host Species. AB - We developed a novel enzyme immunoassay for the detection of group A rotavirus (RVA) antigen in fecal samples of multiple host species. The assay is based on the detection of conserved VP6 protein using anti-recombinant VP6 antibodies as capture antibodies and anti-multiple antigenic peptide (identified and constructed from highly immunodominant epitopes within VP6 protein) antibodies as detector antibodies. The clinical utility of the assay was evaluated using a panel of 914 diarrhoeic fecal samples from four different host species (bovine, porcine, poultry and human) collected from diverse geographical locations in India. Using VP6- based reverse transcription-polymerase chain reaction (RT-PCR) as the gold standard, we found that the diagnostic sensitivity (DSn) and specificity (DSp) of the new assay was high [bovine (DSn = 94.2% & DSp = 100%); porcine (DSn = 94.6% & DSp = 93.3%); poultry (DSn = 74.2% & DSp = 97.7%) and human (DSn = 82.1% & DSp = 98.7%)]. The concordance with RT-PCR was also high [weighted kappa (k) = 0.831-0.956 at 95% CI = 0.711-1.0] as compared to RNA polyacrylamide gel electrophoresis (RNA-PAGE). The performance characteristics of the new immunoassay were comparable to those of the two commercially available ELISA kits. Our results suggest that this peptide-recombinant protein based assay may serve as a preliminary assay for epidemiological surveillance of RVA antigen and for evaluation of vaccine effectiveness especially in low and middle income settings. PMID- 27391109 TI - Control of Imine Exchange Kinetics with Photoswitches to Modulate Self-Healing in Polysiloxane Networks by Light Illumination. AB - Various aldehyde-containing photoswitches have been developed whose reactivity toward amines can be controlled externally. A thermally stable bifunctional diarylethene, which in its ring-closed form exhibits imine formation accelerated by one order of magnitude, was used as a photoswitchable crosslinker and mixed with a commercially available amino-functionalized polysiloxane to yield a rubbery material with viscoelastic and self-healing properties that can be reversibly tuned by irradiation. PMID- 27391108 TI - Reactive Oxygen Species/Hypoxia-Inducible Factor-1alpha/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage. AB - Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell-substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1alpha. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2-related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1alpha/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF 1alpha and PDGF-BB. Pharmacological blocking of HIF-1alpha significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID- 27391110 TI - Changes of Socio-demographic data of clients seeking genetic counseling for hereditary breast and ovarian cancer due to the "Angelina Jolie Effect". AB - BACKGROUND: The purpose of this study was to evaluate socio-demographic characteristics of clients claiming genetic counseling for hereditary breast and ovarian cancer (HBOC) in Austria. Furthermore, changes of these parameters before and after Angelina Jolie's (AJ) disclosure of carrying a BRCA mutation were evaluated. METHODS: In this prospective, nonrandomized study 268 consecutive clients seeking genetic counseling for HBOC at the Medical University of Vienna, Department of Obstetrics and Gynecology, Vienna, Austria between June 2012 and June 2014 were included. Socio-demographic data and source of information about HBOC and genetic counseling were evaluated. First, socio-demographic parameters were compared to the general Austrian population. Second, changes in these parameters after AJ's public disclosure of carrying a BRCA mutation were analyzed. RESULTS: Subjects were more frequent female, younger and higher educated in comparison to Austria's general population (p < 0.001). Furthermore, level of education in participants was higher before than after AJ's disclosure (p = 0.046). Most clients were informed about genetic counseling by physicians. As expected, after AJ's public announcement patients were more frequent advised to genetic counseling by social media (p = 0.043) and family or friends (p = 0.010) than before. CONCLUSIONS: In this present study we could demonstrate that particularly younger and female participants with high educational level attended significantly more often genetic counseling for HBOC. Increased presence of HBOC in media since AJ's disclosure of carrying a BRCA mutation had lead that information and awareness about HBOC was obtained by a wider audience from different social background. PMID- 27391111 TI - Patent filing strategies: perspectives from the Cooperation Council for the Arab States of the Gulf. AB - The protection and enforcement of intellectual property rights has become one of the most contentious issues in global commerce. Much of the traditional growth and development of countries in the Middle East over the past 30 years or so has come from oil and gas revenues. The main areas that have been covered in this article are: synopsis of patenting system in each country, the Cooperation Council for the Arab States of the Gulf patent filing system, patentability subject matter, prosecution of patent application, opposition and/or invalidation action(s) and issues that need to be resolved for an effective patent regime. PMID- 27391112 TI - Acceptability of Salt Fluoridation in a Rural Latino Community in the United States: An Ethnographic Study. AB - Compared to other population groups in the United States, caries (tooth decay) is a disproportionately prevalent disease among Latino populations, especially among low-income and rural sub-groups and children under five years of age. Fluoride is a primary preventive for caries. While water fluoridation is a major and effective public health means for delivering fluoride on a mass scale, it does not reach many rural areas or population groups such as Latinos who eschew drinking water from municipal sources. This study examines the acceptability to such groups of salt fluoridation, an alternate means of delivering fluoride long used on a global scale. An ethnographic study in California's rural Central Valley was performed. Thirty individual interviews and 5 focus groups (N = 61) were conducted in Spanish to investigate low-income Latino migrant caregivers' experiences, views and understandings of domestic salt, oral health, caries prevention and fluoride. Audio data were transcribed, translated, coded and thematically analyzed. Table salt was readily available and frequently consumed. Both adult and child daily sodium consumption was high. Despite a general feeling that it was good, and present in dentifrices or dietary supplements, most participants had little knowledge about fluoride. Concerns were raised about cardio-vascular and other possibly deleterious effects if an increase in salt consumption occurred because fluoridated salt was viewed as having 'extra' benefits. Once informed about fluoride's safety and role in caries prevention, most participants expressed willingness to use fluoridated salt, especially if it benefitted children. Reassurance about its safety and benefits, and demonstration of its taste, were important aspects of acceptance. Taste was paramount. Participants would not consume more fluoridated salt than their current salt as that would result in unpleasant changes in food flavor and taste. While salt fluoridation is acceptable, the feasibility of producing and distributing fluoridated salt in the United States is, however, complex and challenging. PMID- 27391113 TI - Paternity in wild ring-tailed lemurs (Lemur catta): Implications for male mating strategies. AB - In group-living species with male dominance hierarchies where receptive periods of females do not overlap, high male reproductive skew would be predicted. However, the existence of female multiple mating and alternative male mating strategies can call into question single-male monopolization of paternity in groups. Ring-tailed lemurs (Lemur catta) are seasonally breeding primates that live in multi-male, multi-female groups. Although established groups show male dominance hierarchies, male dominance relationships can break down during mating periods. In addition, females are the dominant sex and mate with multiple males during estrus, including group residents, and extra-group males-posing the question of whether there is high or low male paternity skew in groups. In this study, we analyzed paternity in a population of wild L. catta from the Beza Mahafaly Special Reserve in southwestern Madagascar. Paternity was determined with 80-95% confidence for 39 offspring born to nine different groups. We calculated male reproductive skew indices for six groups, and our results showed a range of values corresponding to both high and low reproductive skew. Between 21% and 33% of offspring (3 of 14 or three of nine, counting paternity assignments at the 80% or 95% confidence levels, respectively) were sired by extra-troop males. Males siring offspring within the same group during the same year appear to be unrelated. Our study provides evidence of varying male reproductive skew in different L. catta groups. A single male may monopolize paternity across one or more years, while in other groups, >1 male can sire offspring within the same group, even within a single year. Extra-group mating is a viable strategy that can result in extra-group paternity for L. catta males. PMID- 27391114 TI - Synthesis and Disassembly/Reassembly of Giant Ring-Shaped Polyoxotungstate Oligomers. AB - The disassembly and reassembly of giant molecules are essential processes in controlling the structure and function of biological and artificial systems. In this work, the disassembly and reassembly of a giant ring-shaped polyoxometalate (POM) without isomerization of the monomeric units is reported. The reaction of a hexavacant lacunary POM that is soluble in organic solvents, [P2 W12 O48 ](14-) , with manganese cations gave the giant ring-shaped POM [{gamma-P2 W12 O48 Mn4 (C5 H7 O2 )2 (CH3 CO2 )}6 ](42-) . This POM is a hexamer of manganese-substituted {P2 W12 O48 Mn4 } units, and its inner cavity was larger than any of those previously reported for ring-shaped polyoxotungstates. It was disassembled into monomeric units in acetonitrile, and the removal of the capping organic ligands on the manganese cations led to reassembly into a tetrameric ring-shaped POM, [{gamma-P2 W12 O48 Mn4 (H2 O)6 }4 (H2 O)4 ](24-) . PMID- 27391117 TI - A1 segment hypoplasia associated with cerebral infarction after anterior communicating artery aneurysm rupture. AB - BACKGROUND: Congenital hypoplasia or absence of the A1 segment of the anterior cerebral artery (ACA) has been associated with increased incidence of berry aneurysms at the anterior communicating artery (Acom) complex. It is not known, however, whether this anatomic variant also predisposes patients to complications after aneurysmal subarachnoid hemorrhage. METHODS: Patients were included for analysis if they presented to our institution for clipping or coiling of an Acom aneurysm between the years of 2001 and 2013. Patients were deemed to have cerebral infarction if a new hypodensity in a vascular distribution was visualized on CT imaging. The association between A1 segmental abnormalities and radiologic infarction was subsequently evaluated in a risk-adjusted manner using stepwise multivariable logistic regression analysis. RESULTS: Of 145 patients who presented with aneurysmal subarachnoid hemorrhage after rupture of an ACoM aneurysm, 31 (21.4%) had a hypoplastic or absent A1 segment. On univariate analysis, there was a trend toward an increased rate of radiologic infarction in patients with A1 segment abnormalities (OR 2.11, 95% CI 0.93-4.79; p=0.0757). On multivariable analysis, a hypoplastic or absent A1 segment was significantly associated with an increased rate of radiologic infarction (OR 2.54, 95% CI 1.02 6.43; p = 0.0466). CONCLUSIONS: Our results suggest that a hypoplastic or absent A1 segment is associated with cerebral infarction following subarachnoid hemorrhage from ruptured ACoM aneurysms, indicating a potential need for heightened vigilance and a reduced threshold for therapeutic intervention in patients harboring this abnormality. PMID- 27391116 TI - Systematization of ambiguous genitalia. AB - Sex assignment in newborns depends on the anatomy of the external genitalia, despite this stage being the final in embryogenesis. According to the current view, the genital tubercle is the embryonic precursor of penis and clitoris. It originates from mesenchymal tissue, but mesenchymal cells are arranged across the embryonal body and do not have specific androgen receptors. The nature of the signal that initiates early derivation of the indifferent genital tubercle is unknown at present. The aims of this article are to improve surgical management of intersex disorders and investigate the development of the genital tubercle. Clinical examination of 114 females with various forms of DSD revealed ambiguous (bisexual) external genitalia in 73 patients, and 51 of them underwent feminizing surgery. Intersexuality (ambiguity) in 46,XY patients results from disruptors in the pathways of sex steroid hormones or receptors; in 46,XX females arises from excessive levels of androgens. Systematization of intersex disorders distinguishes the karyotype, gonadal morphology, and genital anatomy to provide a differential diagnosis and guide appropriate surgical management. Modified feminizing clitoroplasty with preservation of the dorsal and ventral neurovascular bundles to retain erogenous sensitivity was performed in females with severe virilization (Prader degree III-V). The outgrowth of the genital tubercle and the fusion of the urethral fold proceed in an ordered fashion; but in some cases of ambiguity, there was discordance due to different pathways. Speculation about the derivation of the genital tubercle have discussed with a literature review. The genital tubercle derives from the following 3 layers: the ectodermal glans of the tubercle, the mesodermal corpora cavernosa and the endodermal urogenital groove. According to the new hypothesis, during the indifferent stages, the 5 sacral somites have to recede from their segmentation and disintegrate: the sclerotomes form the pelvic bones, the fused myotomes follow with their genuine neurotomes and the angiotomes join to the corpora cavernosa of the genital tubercle. Sexual differentiation of external genitalia is final in gender embryogenesis, but surprisingly derivation of the indifferent genital tubercle from 5 somites occurs before gonadal and internal organs development. PMID- 27391118 TI - Physician drug dispensing in Switzerland: association on health care expenditures and utilization. AB - BACKGROUND: Several countries recently reassessed the roles of drug prescribing and dispensing, either by enlarging pharmacists' rights to prescribe (e.g. the US and the United Kingdom) or by limiting physicians' rights to dispense (e.g. Taiwan and South Korea). While integrating the two roles might increase supply and be convenient for patients, concern is that drug mark-ups incite providers to prescribe unnecessary drugs. We aimed to assess the association of physician dispensing (PD) in Switzerland on various outcomes. METHODS: We performed a retrospective cohort study, using health care claims data for patients in the year 2013. The analysis of the association of PD was perfomed using a large patient level dataset and several target variables, including the number of different chemical agents, share of generic drugs, number of visits to physicians and expenditures. Different multivariate econometric models were applied in order to capture the association PD on the target variables. RESULTS: A total of 101'784 patients were enrolled in 2013, whereas 54 % were PD patients. We find that PD is associated with lower pharmaceutical expenditure per patient, which can be explained by an increased use of generic drugs. The decrease is compensated by higher use of physician services. We find no significant impact of physician dispensing on total health care expenditure. CONCLUSIONS: Our study offers insights for policy makers who are (re-)considering the separation between drug prescribing and dispensing, either by allowing physicians to dispense or pharmacists to prescribe certain drugs. In terms of total health care expenditures, we find no difference between the two systems, so we are doubtful that changing dispensing rights are a good measure to contain cost, at least in Switzerland. PMID- 27391121 TI - Whole exome sequencing diagnosis of inborn errors of metabolism and other disorders in United Arab Emirates. AB - BACKGROUND: This study reports on the use of whole exome sequencing (WES) to diagnose children with inborn errors of metabolism and other disorders in United Arab Emirates. METHODS: From January 2012 to December 2014, 85 patients (46 % females) were seen in the metabolic center at Tawam Hospital (Abu Dhabi) and WES testing was requested because definitive diagnoses were not reached by conventional methods. RESULTS: Eighty (93 %) patients were <18 years old and 44 (52 %) were <5 years. Sixty-eight (80 %) patients had neurologic abnormalities. WES facilitated rapid diagnosis in 50 % of the patients, especially those with mitochondrial disorders. Yet, in most cases extensive investigation was required after the results were available. Most patients with confirmed molecular diagnoses had autosomal recessive disorders and were homozygous for the rare alleles. Most patients with autosomal dominant disorders and all patients with X linked disorders had de novo mutations. WES results were negative (no pathogenic variants related to patient phenotype were identified) in six patients and incorrect in two patients. One patient had a reported "deleterious" hemizygous mutation in SLC35A2, c.617_620del (p.Q206fs), suggesting 'congenital disorder of glycosylation, TYPE IIm', but glycosylation studies were normal and healthy brothers had the same mutation. Another patient had "pathogenic" mutation in MCCC2, c.1015G > A (p.V339M), but urine organic acids was normal. WES confirmed inborn errors of metabolism (five mitochondrial diseases, three lysosomal storage diseases, and six other disorders) in 14 patients and genetic disorders (14 neurological diseases and three non-neurological diseases) in 17 patients. Variants of unknown significance were identified in 48 patients; 12 had "confirmed pathologic variants"and 12 had "likely pathologic variants", based on consistent phenotypes, biochemical/ segregation studies, or reported pathogenicity. In 24 patients, the variants were inconsistent with phenotypes or biochemical/ familial studies. CONCLUSIONS: Although WES provided molecular diagnoses, the results required careful interpretations and many patients required additional investigations. This tool is useful when conventional diagnostic methods fail. Staff competence in obtaining consent/ permission, interpreting the findings, and providing the proper counseling are essential before incorporating this technology into routine clinical practices. PMID- 27391119 TI - A comprehensive method for amplicon-based and metagenomic characterization of viruses, bacteria, and eukaryotes in freshwater samples. AB - BACKGROUND: Studies of environmental microbiota typically target only specific groups of microorganisms, with most focusing on bacteria through taxonomic classification of 16S rRNA gene sequences. For a more holistic understanding of a microbiome, a strategy to characterize the viral, bacterial, and eukaryotic components is necessary. RESULTS: We developed a method for metagenomic and amplicon-based analysis of freshwater samples involving the concentration and size-based separation of eukaryotic, bacterial, and viral fractions. Next generation sequencing and culture-independent approaches were used to describe and quantify microbial communities in watersheds with different land use in British Columbia. Deep amplicon sequencing was used to investigate the distribution of certain viruses (g23 and RdRp), bacteria (16S rRNA and cpn60), and eukaryotes (18S rRNA and ITS). Metagenomic sequencing was used to further characterize the gene content of the bacterial and viral fractions at both taxonomic and functional levels. CONCLUSION: This study provides a systematic approach to separate and characterize eukaryotic-, bacterial-, and viral-sized particles. Methodologies described in this research have been applied in temporal and spatial studies to study the impact of land use on watershed microbiomes in British Columbia. PMID- 27391120 TI - Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease. AB - BACKGROUND: The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such responses, which may be beneficial to spirochete transmission. The primary goal of this study was to test the hypothesis that tick saliva, in the context of Borrelia burgdorferi, can have widespread effects on the production of immune mediators in skin. METHODS: A cross-section of tick feeding on skin was examined histologically. Human THP-1 cells stimulated with B. burgdorferi and grown in the presence or absence of tick saliva were examined by human DNA microarray, cytokine bead array, sandwich ELISA, and qRT-PCR. Similar experiments were also conducted using dermal fibroblasts. RESULTS: Tick feeding on skin showed dermal infiltration of histiocytes and granulocytes at the bite location. Changes in monocytic transcript levels during co-culture with B. burgdorferi and saliva indicated that tick saliva had a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8 (CXCL8) and TLR2, but had a stimulatory effect on specific molecules such as the Interleukin 10 receptor, alpha subunit (IL-10RA), a known mediator of the immunosuppressive signal of IL-10. Stimulated cell culture supernatants were analyzed via antigen-capture ELISA and cytokine bead array for inflammatory mediator production. Treatment of monocytes with saliva significantly reduced the expression of several key mediators including IL 6, IL-8 and TNF-alpha. Tick saliva had an opposite effect on dermal fibroblasts. Rather than inhibiting, saliva enhanced production of pro-inflammatory mediators, including IL-8 and IL-6 from these sentinel skin cells. CONCLUSIONS: The effects of ixodid tick saliva on resident skin cells is cell type-dependent. The response to both tick and pathogen at the site of feeding favors pathogen transmission, but may not be wholly suppressed by tick saliva. PMID- 27391123 TI - Nuclear magnetic resonance at millitesla fields using a zero-field spectrometer. AB - We describe new analytical capabilities for nuclear magnetic resonance (NMR) experiments in which signal detection is performed with chemical resolution (via spin-spin J couplings) in the zero to ultra-low magnetic field region, below 1MUT. Using magnetic fields in the 100MUT to 1mT range, we demonstrate the implementation of conventional NMR pulse sequences with spin-species selectivity. PMID- 27391122 TI - Dengue score: a proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection. AB - BACKGROUND: There are several limitations in diagnosing plasma leakage using the World Health Organization (WHO) guidelines of dengue hemorrhagic fever. We conducted a study to develop a dengue scoring system to predict pleural effusion and/or ascites using routine laboratory parameters. METHODS: A prospective observational study was carried out at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Dengue-infected adults admitted on the third febrile day from March, 2010 through August, 2015 were included in the study. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites and to convert the prediction model into a scoring system. RESULTS: A total of 172 dengue-infected adults were enrolled in the study. Of the 172 patients, 101 (58.7 %) developed pleural effusion and/or ascites. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites in dengue-infected adults. The predictors were scored based on the following calculations: hemoconcentration >=15.1 % had a score of 1 (OR, 3.11; 95 % CI, 1.41-6.88), lowest albumin concentration at critical phase <=3.49 mg/dL had a score of 1 (OR, 4.48; 95 % CI, 1.87-10.77), lowest platelet count <=49,500/MUL had a score of 1 (OR, 3.62; 95 % CI, 1.55-8.49), and elevated ratio of AST >=2.51 had a score of 1 (OR 2.67; 95 % CI, 1.19-5.97). At a cut off of >= 2, the Dengue Score predicted pleural effusion and/or ascites diagnosis with positive predictive value of 79.21 % and negative predictive value of 74.63 %. This prediction model is suitable for calibration and good discrimination. CONCLUSIONS: We have developed a Dengue Score that could be used to identify pleural effusion and/or ascites and might be useful to stratify dengue-infected patients at risk for developing severe dengue. PMID- 27391124 TI - Relations Between Past-Week Physical Activity and Recent Nonsuicidal Self-Injury in Treatment-Seeking Psychiatric Adults. AB - OBJECTIVE: This research study examines the relationship between past-week physical activity and recent (i.e., within the past 30 days) nonsuicidal self injury (NSSI) in a sample of treatment-seeking adults. METHOD: Participants included 353 (49.29% female; mean age = 35.16 years) adults attending a partial hospitalization program for acute psychiatric issues. Data were extracted from the program's admission battery of computer-based self-report measures completed by each participant on the first treatment day. RESULTS: Participants with a recent history of NSSI (i.e., within the past 30 days) engaged in significantly less past-week physical activity than those without a history of NSSI. Group differences remained significant while controlling for anxiety, but not depression. CONCLUSION: Results suggest that, on average, individuals who have never engaged in NSSI exercise more in the week prior to entering the partial hospital program than those who have a recent history of NSSI. Regular physical activity may be an interesting area of study to explore as a promising adjunctive intervention for NSSI (e.g., vigorous exercise as a way to tolerate distress and manage urges to self-injure). PMID- 27391125 TI - Postoperative pneumatosis intestinalis (PI) and portal venous gas (PVG) may indicate bowel necrosis: a 52-case study. AB - BACKGROUND: The significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) is controversial. This retrospective study evaluated the risk factors for bowel necrosis in patients with PI and/or PVG. METHODS: Between 2002 and 2015, 52 patients were diagnosed with PI and/or PVG and were included in this study. The patients were classified according to the presence or absence of bowel necrosis in surgical findings or at autopsy. Patient characteristics and clinical findings related to bowel necrosis were investigated. RESULTS: Bowel necrosis was diagnosed in 17 (32.7 %) patients. Amongst these 17, 10 patients received salvage surgical intervention, and seven of those diagnosed with bowel necrosis survived after the operation. The remaining 35 patients received conservative treatment with or without exploratory laparotomy. Between patients with and without bowel necrosis, laboratory data revealed significant differences in the levels of C reactive protein (P = 0.0038), creatinine (P = 0.0054), and lactate (P = 0.045); clinical findings showed differences in abdominal pain (P = 0.019) and peritoneal irritation signs (P = 0.016); computed tomography detected ascites (P = 0.011) and changes of bowel wall enhancement (P = 0.03) that were significantly higher in patients with bowel necrosis. The rate of PI and/or PVG detected in patients postoperatively was significantly higher in patients with bowel necrosis (P < 0.0001). Multivariate analysis showed that bowel necrosis was significantly more likely when PI or PVG was detected in postoperative patients than in patients who had not had surgery (P = 0.003). CONCLUSIONS: PI and/or PVG, alone, are not automatically indicative of bowel necrosis. However, when these conditions occur postoperatively, they indicate bowel necrosis requiring reoperation. PMID- 27391126 TI - The excited spin-triplet state of a charged exciton in quantum dots. AB - We report on spectroscopic studies of resonances related to ladder of states of a charged exciton in single GaAlAs/AlAs quantum dot structures. Polarization resolved photoluminescence, photoluminescence excitation and photon-correlation measurements were performed at low (T = 4.2 K) temperature also in magnetic field applied in Faraday configuration. The investigated resonances are assigned to three different configurations of a positively charged exciton. Together with a singlet ground state and a conventional triplet state (involving an electron from the ground state electronic s-shell), an excited triplet state, which involved an electron from the excited electronic p-shell was identified in single dots. The appearance of an emission line related to the latter complex is due to a partially suppressed electron relaxation in the investigated dots. An analysis of this emission line allows us to scrupulously determine properties of the excited triplet state and compare them with those of the conventional triplet state. Both triplets exhibit similar patterns of anisotropic fine structure and Zeeman splitting, however their amplitudes significantly differ for those two states. Presented results emphasize the role of the symmetry of the electronic state on the properties of the triplet states of two holes + electron excitonic complex. PMID- 27391127 TI - A descriptive study of the participation of children and adolescents in activities outside school. AB - BACKGROUND: Knowledge about patterns of participation can be used to highlight groups of children and adolescents with low attendance, or low involvement in activities and who may therefore be at risk of mental or physical health concerns. This study used the Children's Assessment of Participation and Enjoyment (CAPE) and the Preferences for Activity of Children (PAC) to describe the patterns of participation of children and adolescents in activities outside mandated school in Victoria, Australia. METHODS: A cross-sectional survey of Victorian children and adolescents was conducted. Eligible participants were aged 6 to 18 years, enrolled in mainstream schools, with sufficient English language skills to complete the questionnaires. Parents of participants completed a demographic questionnaire. Sample representativeness was assessed against Victorian population statistics for gender, school type, language spoken at home and socio-economic status. Data for the CAPE and PAC were summarised using descriptive statistics. Patterns of activity diversity by age were assessed using curve estimation, with additional analyses to describe differences between genders. RESULTS: Of 9337 potential participants targeted through school advertising, 512 agreed (5.5 % consent rate), and 422 questionnaires were returned (82.4 % response rate). The sample was representative in terms of gender and language. Compared to the Victorian population, a slightly higher proportion of participants attended Government and Catholic schools and there was evidence of marginally greater socioeconomic resources than the population average. A broad range of recreational, active physical, social, skill-based and self improvement activities were completed by all age groups. There was a reduction in the number and enjoyment of recreational activities with increasing age. In contrast, there was relative stability in intensity, frequency and preference scores across the age-groups for all activity types. Female participants typically took part in more activities (higher diversity scores), more intensely, with higher enjoyment and had higher preferences for each activity type than males, with the exception of active physical activities. CONCLUSIONS: This study provides evidence of the participation patterns of typically developing children and adolescents in activities outside school. The findings have implications for researchers, clinicians and educators for comparative purposes and to inform future research. PMID- 27391128 TI - Neighborhood socioeconomic characteristics and statin medication in patients with myocardial infarction: a Swedish nationwide follow-up study. AB - BACKGROUND: Coronary heart disease (CHD) and myocardial infarction (MI) are associated with neighborhood-level socioeconomic status (SES). Statins are important drugs for secondary prevention of MI. However, no study has determined whether neighborhood-level SES is associated with statin medication in MI patients. We aimed to determine whether there is a difference in statin medication rate in MI patients across different levels of neighborhood SES. METHODS: All patients in Sweden, diagnosed with incident MI from January 1st, 2000 until December 31(st) 2010, were followed (n = 116,840). Of these, 89.7 % received statin medication. Data were analyzed by multilevel logistic regression, with individual-level characteristics (age, marital status, family income, educational attainment, country of origin, urban/rural status and comorbidities/chronic conditions related to MI) as covariates. RESULTS: Low neighborhood-level SES was significantly associated with low statin medication rate (Odds Ratio 0.80). In the full model, which took into account individual level socioeconomic characteristics and MI comorbidities, the odds no longer remained significant. CONCLUSIONS: Individual-level approaches may be most important in health care policies regarding statin medication in MI patients. PMID- 27391129 TI - Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa. AB - Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness. PMID- 27391130 TI - The Client's Perspective on Voluntary Stuttering. AB - PURPOSE: Voluntary stuttering is a strategy that has been suggested for use in the clinical literature but has minimal empirical data regarding treatment outcomes. The purpose of the present study is to explore client perspectives regarding the impact of the use of this strategy on the affective, behavioral, and cognitive components of stuttering. METHOD: The present study used an original survey designed to explore the intended purpose. A total of 206 adults who stutter were included in the final data corpus. Responses were considered with respect to the type of voluntary stuttering the participants reportedly produced and the location of use. RESULTS: A client perceives significantly greater affective, behavioral, and cognitive benefits from voluntary stuttering when the production is closely matched to the client's actual stutter and when it is used outside the clinical environment. CONCLUSIONS: To enhance client perception of associated benefits, clinicians should encourage use of voluntary stuttering that closely matches the client's own stuttering. Clinicians should also facilitate practice of voluntary stuttering outside of the therapy room. Finally, clinicians should be aware that clients, at least initially, may not perceive any benefits from the use of this strategy. PMID- 27391131 TI - Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model. AB - The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (MUCT). After FGF-2 (0.3%) or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC) were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using MUCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological healing process. PMID- 27391132 TI - Toward Quantitatively Accurate Calculation of the Redox-Associated Acid-Base and Ligand Binding Equilibria of Aquacobalamin. AB - Redox processes in complex transition metal-containing species are often intimately associated with changes in ligand protonation states and metal coordination number. A major challenge is therefore to develop consistent computational approaches for computing pH-dependent redox and ligand dissociation properties of organometallic species. Reduction of the Co center in the vitamin B12 derivative aquacobalamin can be accompanied by ligand dissociation, protonation, or both, making these properties difficult to compute accurately. We examine this challenge here by using density functional theory and continuum solvation to compute Co-ligand binding equilibrium constants (Kon/off), pKas, and reduction potentials for models of aquacobalamin in aqueous solution. We consider two models for cobalamin ligand coordination: the first follows the hexa, penta, tetra coordination scheme for Co(III), Co(II), and Co(I) species, respectively, and the second model features saturation of each vacant axial coordination site on Co(II) and Co(I) species with a single, explicit water molecule to maintain six directly interacting ligands or water molecules in each oxidation state. Comparing these two coordination schemes in combination with five dispersion corrected density functionals, we find that the accuracy of the computed properties is largely independent of the scheme used, but including only a continuum representation of the solvent yields marginally better results than saturating the first solvation shell around Co throughout. PBE performs best, displaying balanced accuracy and superior performance overall, with RMS errors of 80 mV for seven reduction potentials, 2.0 log units for five pKas and 2.3 log units for two log Kon/off values for the aquacobalamin system. Furthermore, we find that the BP86 functional commonly used in corrinoid studies suffers from erratic behavior and inaccurate descriptions of Co-axial ligand binding, leading to substantial errors in predicted pKas and Kon/off values. These findings demonstrate the effectiveness of the present approach for computing electrochemical and thermodynamic properties of a complex transition metal containing cofactor. PMID- 27391133 TI - Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening. AB - Here we report the discovery of a selective inhibitor of Aurora A, a key regulator of cell division and potential anticancer target. We used the atom category extended ligand overlap score (xLOS), a 3D ligand-based virtual screening method recently developed in our group, to select 437 shape and pharmacophore analogs of reference kinase inhibitors. Biochemical screening uncovered two inhibitor series with scaffolds unprecedented among kinase inhibitors. One of them was successfully optimized by structure-based design to a potent Aurora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases. This inhibitor locks Aurora A in an inactive conformation and disrupts binding to its activator protein TPX2, which impairs Aurora A localization at the mitotic spindle and induces cell division defects. This phenotype can be rescued by inhibitor-resistant Aurora A mutants. The inhibitor furthermore does not induce Aurora B specific effects in cells. PMID- 27391134 TI - Recombinant cloning strategies for protein expression. AB - A variety of methods to create specific constructs for protein expression, in a broad range of organisms, are available nowadays. Restriction enzyme-free, ligation-independent and recombinase-based cloning methods have enabled high throughput protein expression for structural and functional studies. These methods are also instrumental for modification of target genes including gene truncations, site-specific mutagenesis and domain swapping. Here, we describe the most common cloning techniques that are currently at hand for recombinant protein expression studies, including a brief overview of techniques associated with co expression experiments. We also provide an inventory of many of the available reagents for the various cloning methods, and an overview for some computational tools that can help with the design of expression constructs. PMID- 27391135 TI - 3-Hydrazinoindolin-2-one derivatives: Chemical classification and investigation of their targets as anticancer agents. AB - Isatin is a well acknowledged pharmacophore in many clinically approved drugs used for treatment of cancer. 3-Hydrazinoindolin-2-one, as a derivative of isatin, represents a pharmacophore of an important class of biologically active pharmaceutical agents by virtue of their diverse biological activities. In this review, anticancer activity will be on focus for compounds derived from 3 hydrazinoindolin-2-one. They are classified according to their chemical structure into nine different classes. In each class, different compounds were browsed, showing their anticancer activity and their potential targets. Moreover, crystallographic data or docking studies were highlighted for some compounds, when available, to provide a deep understanding of their mechanisms of action. PMID- 27391136 TI - Design of a MEMS-Based Oscillator Using 180nm CMOS Technology. AB - Micro-electro mechanical system (MEMS) based oscillators are revolutionizing the timing industry as a cost effective solution, enhanced with more features, superior performance and better reliability. The design of a sustaining amplifier was triggered primarily to replenish MEMS resonator's high motion losses due to the possibility of their 'system-on-chip' integrated circuit solution. The design of a sustaining amplifier observing high gain and adequate phase shift for an electrostatic clamp-clamp (C-C) beam MEMS resonator, involves the use of an 180nm CMOS process with an unloaded Q of 1000 in realizing a fixed frequency oscillator. A net 122dBOmega transimpedance gain with adequate phase shift has ensured 17.22MHz resonant frequency oscillation with a layout area consumption of 0.121 mm2 in the integrated chip solution, the sustaining amplifier draws 6.3mW with a respective phase noise of -84dBc/Hz at 1kHz offset is achieved within a noise floor of -103dBC/Hz. In this work, a comparison is drawn among similar design studies on the basis of a defined figure of merit (FOM). A low phase noise of 1kHz, high figure of merit and the smaller size of the chip has accredited to the design's applicability towards in the implementation of a clock generative integrated circuit. In addition to that, this complete silicon based MEMS oscillator in a monolithic solution has offered a cost effective solution for industrial or biomedical electronic applications. PMID- 27391137 TI - A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease. AB - BACKGROUND: Congenital heart disease (CHD) is the most prevalent type of birth defect in human, with high morbidity in infant. Several genes essential for heart development have been identified. GATA4 is a pivotal transcription factor that can regulate the cardiac development. Many GATA4 mutations have been identified in patients with different types of CHD. AIMS: In this study, the NKX2-5, HAND1 and GATA4 coding regions were sequenced in a family spanning three generations in which seven patients had CHD. Disease-causing potential variation in this family was evaluated by bioinformatics programs and the transcriptional activity of mutant protein was analyzed by the dual luciferase reporter assay. RESULTS: A novel GATA4 mutation, c.C931T (p.R311W), was identified and co-segregated with the affected patients in this family. The bioinformatics programs predicted this heterozygous mutation to be deleterious and the cross-species alignment of GATA4 sequences showed that the mutation occurred within a highly conserved amino acid. Even though it resided in the nuclear localization signal domain, the mutant protein didn't alter its intracellular distribution. Nevertheless, further luciferase reporter assay demonstrated that the p.R311W mutation reduced the ability of GATA4 to activate its downstream target gene. CONCLUSIONS: Our study identified a novel mutation in GATA4 that likely contributed to the CHD in this family. This finding expanded the spectrum of GATA4 mutations and underscored the pathogenic correlation between GATA4 mutations and CHD. PMID- 27391138 TI - Jungle Giants: Assessing Sustainable Harvesting in a Difficult-to-Survey Species (Python reticulatus). AB - Sustainability of wildlife harvests is critical but difficult to assess. Evaluations of sustainability typically combine modelling with the measurement of underlying abundances. For many taxa harvested in developing countries, however, abundances are near-impossible to survey and a lack of detailed ecological information impedes the reliability of models. In such cases, repeated surveys of the attributes of harvested individuals may provide more robust information on sustainability. If the numbers, sizes and other demographic attributes of animals taken for the commercial trade do not change over biologically significant time intervals (decades), there is a prima facie case that the harvest is indeed sustainable. Here, we report the results of examinations of > 4,200 reticulated pythons (Python reticulatus) taken for the commercial leather industry in northern and southern Sumatra, Indonesia. The numbers, mean body sizes, clutch sizes, sizes at maturity and proportion of giant specimens have not decreased between our first surveys (1995) and repeat surveys (2015). Thus, despite assumptions to the contrary, the harvest appears to be sustainable. We use our data to inform the design of future monitoring programs for this species. Our study underpins the need for robust science to inform wildlife trade policy and decision-making, and urges wildlife managers to assess sustainability of difficult-to-survey terrestrial wildlife by drawing inferences directly from the harvest itself. PMID- 27391139 TI - Weed seed inactivation in soil mesocosms via biosolarization with mature compost and tomato processing waste amendments. AB - BACKGROUND: Biosolarization is a fumigation alternative that combines passive solar heating with amendment-driven soil microbial activity to temporarily create antagonistic soil conditions, such as elevated temperature and acidity, that can inactivate weed seeds and other pest propagules. The aim of this study was to use a mesocosm-based field trial to assess soil heating, pH, volatile fatty acid accumulation and weed seed inactivation during biosolarization. RESULTS: Biosolarization for 8 days using 2% mature green waste compost and 2 or 5% tomato processing residues in the soil resulted in accumulation of volatile fatty acids in the soil, particularly acetic acid, and >95% inactivation of Brassica nigra and Solanum nigrum seeds. Inactivation kinetics data showed that near complete weed seed inactivation in soil was achieved within the first 5 days of biosolarization. This was significantly greater than the inactivation achieved in control soils that were solar heated without amendment or were amended but not solar heated. CONCLUSION: The composition and concentration of organic matter amendments in soil significantly affected volatile fatty acid accumulation at various soil depths during biosolarization. Combining solar heating with organic matter amendment resulted in accelerated weed seed inactivation compared with either approach alone. (c) 2016 Society of Chemical Industry. PMID- 27391140 TI - Model-Based Approaches for Teaching and Practicing Personality Assessment. AB - Psychological assessment is a complex professional skill. Competence in assessment requires an extensive knowledge of personality, neuropsychology, social behavior, and psychopathology, a background in psychometrics, familiarity with a range of multimethod tools, cognitive flexibility, skepticism, and interpersonal sensitivity. This complexity makes assessment a challenge to teach and learn, particularly as the investment of resources and time in assessment has waned in psychological training programs over the last few decades. In this article, we describe 3 conceptual models that can assist teaching and learning psychological assessments. The transtheoretical model of personality provides a personality systems-based framework for understanding how multimethod assessment data relate to major personality systems and can be combined to describe and explain complex human behavior. The quantitative psychopathology-personality trait model is an empirical model based on the hierarchical organization of individual differences. Application of this model can help students understand diagnostic comorbidity and symptom heterogeneity, focus on more meaningful high order domains, and identify the most effective assessment tools for addressing a given question. The interpersonal situation model is rooted in interpersonal theory and can help students connect test data to here-and-now interactions with patients. We conclude by demonstrating the utility of these models using a case example. PMID- 27391142 TI - Cobalt(III)-Catalyzed C-C Coupling of Arenes with 7-Oxabenzonorbornadiene and 2 Vinyloxirane via C-H Activation. AB - Co(III)-catalyzed mild C-C couplings of arenes with strained rings such as 7 oxabenzonorbornadienes and 2-vinyloxirane have been realized. The transformation is proposed to undergo ortho C-H activation, olefin insertion, and subsequent beta-oxygen elimination. A broad range of synthetically useful functional groups are compatible, thus providing a new entry to access diversely 2-functionalized indoles. PMID- 27391141 TI - Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway. AB - Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC), a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6-4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke. PMID- 27391143 TI - Melanoma risk in patients with rheumatoid arthritis treated with tumour necrosis factor alpha inhibitors: a systematic review and meta-analysis. AB - Clinicians are concerned that treatment of rheumatoid arthritis (RA) with tumour necrosis factor alpha antagonists (TNFalpha biologics) may increase patients' risk of melanoma compared with treatment with nonbiologic disease-modifying antirheumatic drugs (nbDMARDS). We aimed to assess the risk of melanoma in RA patients treated with TNFalpha biologics compared with RA patients treated with nbDMARDS. A secondary aim was to quantify the risk of melanoma in RA patients treated with TNFalpha biologics compared with the general population. We carried out a systematic review and meta-analysis searching Medline, Embase and the ISI Science Citation Index databases to January 2016. Cohort studies that enabled a quantitative assessment of the risk of melanoma in RA patients treated with TNFalpha biologics compared with either RA patients treated with nbDMARDS or the general population or both were included. Data were pooled using a random-effects model. From 812 articles, we identified six that fulfilled the inclusion criteria. Four studies reported on the risk of melanoma in RA patients treated with TNFalpha biologics compared with those treated with nbDMARDS, with a pooled effect estimate of 1.60 (95% confidence interval 1.16-2.19). Five reported on the risk of melanoma in RA patients treated with TNFalpha biologics compared with the general population, and the pooled effect estimate was 1.87 (95% confidence interval 1.53-2.30). There was no significant heterogeneity in either analysis. This systematic review and meta-analysis does not allay clinician's fears and, while awaiting further evidence from large collaborative studies, this patient population may benefit from regular skin checks and counselling to avoid excessive sun exposure. PMID- 27391144 TI - Intratumoral expression of cyclooxygenase-2 (COX-2) is a negative prognostic marker for patients with cutaneous melanoma. AB - Because of the well-known heterogeneity of melanomas, prognosis of the disease is often difficult to assess even for lesions classified in similar stages. The aim of this study was to assess the usefulness of COX-2 as a melanoma prognostic marker and to establish an optimum algorithm for analysis of COX-2 expression levels in lesions of interest. Expression of COX-2 was detected immunohistochemically in standard sections of formalin-fixed paraffin-embedded tissue samples of 85 primary melanomas, 36 lymph node metastases, and five skin metastases including 39 cases of paired primary and metastatic lesions obtained from the same patient. Enhanced expression of COX-2 in primary melanomas is an indicator of poorer prognosis. A significant correlation was found between high expression of COX-2 in primary lesions and shorter survival. The enhancement of COX-2 expression is also positively correlated with other prognostic factors such as tumor thickness and infiltration level, ulceration, high mitotic index, more invasive histologic type, vertical growth phase, and lymph node metastasis. On the whole, the results suggest that intratumoral expression of COX-2 is a strong negative prognostic marker for patients with melanoma. Moreover, our work shows that a simple and objective immunohistochemical scoring algorithm involving the determination of only a percentage fraction of positively stained cells is sufficient to obtain the prognostic information. PMID- 27391145 TI - Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets. AB - When it comes to neuroscience, pigs represent an important animal model due to their resemblance with humans' brains for several patterns including anatomy and developmental stages. Cerebrospinal fluid (CSF) is a relatively easy-to-collect specimen that can provide important information about neurological health and function, proving its importance as both a diagnostic and biomedical monitoring tool. Consequently, it would be of high scientific interest and value to obtain more standard physiological information regarding its composition and dynamics for both swine pathology and the refinement of experimental protocols. Recently, proton nuclear magnetic resonance (1H NMR) spectroscopy has been applied in order to analyze the metabolomic profile of this biological fluid, and results showed the technique to be highly reproducible and reliable. The aim of the present study was to investigate in both qualitative and quantitative manner the composition of Cerebrospinal Fluid harvested form healthy newborn (5 days old-P5) and young (30-P30 and 50-P50 days old) piglets using 1H NMR Spectroscopy, and to analyze any possible difference in metabolites concentration between age groups, related to age and Blood-Brain-Barrier maturation. On each of the analyzed samples, 30 molecules could be observed above their limit of quantification, accounting for 95-98% of the total area of the spectra. The concentrations of adenine, tyrosine, leucine, valine, 3-hydroxyvalerate, 3-methyl-2-oxovalerate were found to decrease between P05 and P50, while the concentrations of glutamine, creatinine, methanol, trimethylamine and myo-inositol were found to increase. The P05-P30 comparison was also significant for glutamine, creatinine, adenine, tyrosine, leucine, valine, 3-hydroxyisovalerate, 3-methyl-2-oxovalerate, while for the P30-P50 comparison we found significant differences for glutamine, myo-inositol, leucine and trimethylamine. None of these molecules showed at P30 concentrations outside the P05 -P50 range. PMID- 27391146 TI - Mosquitocidal Effect of Glycosmis pentaphylla Leaf Extracts against Three Mosquito Species (Diptera: Culicidae). AB - BACKGROUND: The resistance status of malaria vectors to different classes of insecticides used for public health has raised concern for vector control programmes. Alternative compounds to supplement the existing tools are important to be searched to overcome the existing resistance and persistence of pesticides in vectors and the environment respectively. The mosquitocidal effects of Glycosmis pentaphylla using different solvents of acetone, methanol, chloroform and ethyl acetate extracts against three medically important mosquito vectors was conducted. METHODS: Glycosmis pentaphylla plant leaves were collected from Kolli Hills, India. The WHO test procedures for larval and adult bioassays were used to evaluate extracts against mosquito vectors, and the chemical composition of extracts identified using GC-MS analysis. RESULTS: The larvicidal and adulticidal activity of G. pentaphylla plant extracts clearly impacted the three species of major mosquitoes vectors. Acetone extracts had the highest larvicidal effect against An. stephensi, Cx. quinquefasciatus and Ae. aegypti with the LC50 and LC90 values of 0.0004, 138.54; 0.2669, 73.7413 and 0.0585, 303.746 mg/ml, respectively. The LC50 and LC90 adulticide values of G. pentaphylla leaf extracts in acetone, methanol, chloroform and ethyl acetate, solvents were as follows for Cx. quinquefasciatus, An. stephensi and Ae. Aegypti: 2.957, 5.458, 2.708, and 4.777, 3.449, 6.676 mg/ml respectively. The chemical composition of G. pentaphylla leaf extract has been found in 20 active compounds. CONCLUSIONS: The plant leaf extracts of G. pentaphylla bioactive molecules which are effective and can be developed as an eco-friendly approach for larvicides and adulticidal mosquitoes vector control. Detailed identification and characterization of mosquitocidal effect of individual bioactive molecules ingredient may result into biodegradable effective tools for the control of mosquito vectors. PMID- 27391147 TI - A Blind Test of the Younger Dryas Impact Hypothesis. AB - The Younger Dryas Impact Hypothesis (YDIH) states that North America was devastated by some sort of extraterrestrial event ~12,800 calendar years before present. Two fundamental questions persist in the debate over the YDIH: Can the results of analyses for purported impact indicators be reproduced? And are the indicators unique to the lower YD boundary (YDB), i.e., ~12.8k cal yrs BP? A test reported here presents the results of analyses that address these questions. Two different labs analyzed identical splits of samples collected at, above, and below the ~12.8ka zone at the Lubbock Lake archaeological site (LL) in northwest Texas. Both labs reported similar variation in levels of magnetic micrograins (>300 mg/kg >12.8ka and <11.5ka, but <150 mg/kg 12.8ka to 11.5ka). Analysis for magnetic microspheres in one split, reported elsewhere, produced very low to nonexistent levels throughout the section. In the other split, reported here, the levels of magnetic microspherules and nanodiamonds are low or nonexistent at, below, and above the YDB with the notable exception of a sample <11,500 cal years old. In that sample the claimed impact proxies were recovered at abundances two to four orders of magnitude above that from the other samples. Reproducibility of at least some analyses are problematic. In particular, no standard criteria exist for identification of magnetic spheres. Moreover, the purported impact proxies are not unique to the YDB. PMID- 27391148 TI - Nanoporous Membranes for Microfluidic Concentration Prior to Electrophoretic Separation of Proteins in Urine. AB - A microfluidic device with two nanoporous membranes was developed to seamlessly integrate sample preparation and electrophoretic separation of proteins. The device was fabricated by sandwiching two nanoporous polycarbonate track etched (PCTE) membranes with differently sized nanopores between PDMS slabs containing embedded microchannels. The first membrane contained larger (100 nm) pores and served as an initial filter to screen out particles, cells and larger proteins. The second membrane contained smaller pores (10 nm) which facilitated transport of inorganic ions and small organic molecules, but not proteins. The sequential combination of these two membranes allows proteins to be concentrated and purified simultaneously. The device was used for the sample-in/answer-out quantification of albumin in human urine within 2.5 min with an improvement in sensitivity of 500 fold compared to a normal pinched injection using fluorescence detection. The linear range of was 0-100 MUg mL(-1), with a LOD of 1.5 MUg mL(-1) covering the diagnostic level of microalbuminuria of 30 MUg mL(-1). The presented device, which is simple to make and use, provides a quantitative alternative for point-of-care detection of proteins, as demonstrated through its application to albumin in urine for the diagnoisis of (micro)albuminuria. PMID- 27391149 TI - Nystagmus Does Not Limit Reading Ability in Albinism. AB - PURPOSE: Subjects with albinism usually suffer from nystagmus and reduced visual acuity, which may impair reading performance. The contribution of nystagmus to decreased reading ability is not known. Low vision and nystagmus may have an additive effect. We aimed to address this question by motion compensation of the nystagmus in affected subjects and by simulating nystagmus in healthy controls. METHODS: Reading speed and eye movements were assessed in 9 subjects with nystagmus associated with albinism and in 12 healthy controls. We compared the reading ability with steady word presentation and with words presented on a gaze contingent display where words move in parallel to the nystagmus and thus correct for the nystagmus. As the control, healthy subjects were asked to read words and texts in steady reading conditions as well as text passages that moved in a pattern similar to nystagmus. RESULTS: Correcting nystagmus with a gaze contingent display neither improved nor reduced the reading speed for single words. Subjects with nystagmus and healthy participants achieved comparable reading speed when reading steady texts. However, movement of text in healthy controls caused a significantly reduced reading speed and more regressive saccades. CONCLUSIONS: Our results argue against nystagmus as the rate limiting factor for reading speed when words were presented in high enough magnification and support the notion that other sensory visual impairments associated with albinism (for example reduced visual acuity) might be the primary causes for reading impairment. PMID- 27391150 TI - CNS germinomas are characterized by global demethylation, chromosomal instability and mutational activation of the Kit-, Ras/Raf/Erk- and Akt-pathways. AB - CNS germinomas represent a unique germ cell tumor entity characterized by undifferentiated tumor cells and a high response rate to current treatment protocols. Limited information is available on their underlying genomic, epigenetic and biological alterations. We performed a genome-wide analysis of genomic copy number alterations in 49 CNS germinomas by molecular inversion profiling. In addition, CpG dinucleotide methylation was studied by immunohistochemistry for methylated cytosine residues. Mutational analysis was performed by resequencing of candidate genes including KIT and RAS family members. Ras/Erk and Akt pathway activation was analyzed by immunostaining with antibodies against phospho-Erk, phosho-Akt, phospho-mTOR and phospho-S6. All germinomas coexpressed Oct4 and Kit but showed an extensive global DNA demethylation compared to other tumors and normal tissues. Molecular inversion profiling showed predominant genomic instability in all tumors with a high frequency of regional gains and losses including high level gene amplifications. Activating mutations of KIT exons 11, 13, and 17 as well as a case with genomic KIT amplification and activating mutations or amplifications of RAS gene family members including KRAS, NRAS and RRAS2 indicated mutational activation of crucial signaling pathways. Co-activation of Ras/Erk and Akt pathways was present in 83% of germinomas. These data suggest that CNS germinoma cells display a demethylated nuclear DNA similar to primordial germ cells in early development. This finding has a striking coincidence with extensive genomic instability. In addition, mutational activation of Kit-, Ras/Raf/Erk- and Akt- pathways indicate the biological importance of these pathways and their components as potential targets for therapy. PMID- 27391151 TI - MLN0128, a novel mTOR kinase inhibitor, disrupts survival signaling and triggers apoptosis in AML and AML stem/ progenitor cells. AB - mTOR activation leads to enhanced survival signaling in acute myeloid leukemia (AML) cells. The active-site mTOR inhibitors (asTORi) represent a promising new approach to targeting mTOR in AKT/mTOR signaling. MLN0128 is an orally administered, second-generation asTORi, currently in clinical development. We examined the anti-leukemic effects and the mechanisms of action of MLN0128 in AML cell lines and primary samples, with a particular focus on its effect in AML stem/progenitor cells. MLN0128 inhibited cell proliferation and induced apoptosis in AML by attenuating the activity of mTOR complex 1 and 2. Using time-of-flight mass cytometry, we demonstrated that MLN0128 selectively targeted and functionally inhibited AML stem/progenitor cells with high AKT/mTOR signaling activity. Using the reverse-phase protein array technique, we measured expression and phosphorylation changes in response to MLN0128 in 151 proteins from 24 primary AML samples and identified several pro-survival pathways that antagonize MLN0128-induced cellular stress. A combined blockade of AKT/mTOR signaling and these pro-survival pathways facilitated AML cell killing. Our findings provide a rationale for the clinical use of MLN0128 to target AML and AML stem/progenitor cells, and support the use of combinatorial multi-targeted approaches in AML therapy. PMID- 27391153 TI - Carboxyl-terminal truncated HBx contributes to invasion and metastasis via deregulating metastasis suppressors in hepatocellular carcinoma. AB - Hepatitis B virus (HBV) X protein (HBx), a trans-regulator, is frequently expressed in truncated form without carboxyl-terminus in hepatocellular carcinoma (HCC), but its functional mechanisms are not fully defined. In this report, we investigated frequency of this natural HBx mutant in HCCs and its functional significance. In 102 HBV-infected patients with HCC, C-terminal truncation of HBx, in contrast to full-length HBx, were more prevalent in tumors (70.6%) rather than adjacent non-tumorous tissues (29.4%) (p = 0.0032). Furthermore, two naturally-occurring HBx variants (HBxDelta31), which have 31 amino acids (aa) deleted (codons 123-125/124-126) at C-terminus were identified in tumors and found that the presence of HBxDelta31 significantly correlated with intrahepatic metastasis. We also show that over-expression of HBxDelta31 enhanced hepatoma cell invasion in vitro and metastasis in vivo compared to full-length HBx. Interestingly, HBxDelta31 exerts this function via down-regulating Maspin, RhoGDIalpha and CAPZB, a set of putative metastasis-suppressors in HCC, in part, by enhancing the binding of transcriptional repressor, myc-associated zinc finger protein (MAZ) to the promoters through physical association with MAZ. Notably, these HBxDelta31-repressed proteins were also significantly lower expression in a subset of HCC tissues with C-terminal HBx truncation than the adjacent non tumorous tissues, highlighting the clinical significance of this novel HBxDelta31 driven metastatic molecular cascade. Our data suggest that C-terminal truncation of HBx, particularly breakpoints at 124aa, plays a role in enhancing hepatoma cell invasion and metastasis by deregulating a set of metastasis-suppressors partially through MAZ, thus uncovering a novel mechanism for the progression of HBV-associated hepatocarcinogenesis. PMID- 27391152 TI - Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival. AB - Colorectal tumors arise with genomic and epigenomic alterations through interactions between neoplastic cells, immune cells, and microbiota that vary along the proximal to distal axis of colorectum. Long interspersed nucleotide element-1 (LINE-1) hypomethylation in colorectal cancer has been associated with worse clinical outcome. Utilizing 1,317 colon and rectal carcinoma cases in two U.S.-nationwide prospective cohort studies, we examined patient survival according to LINE-1 methylation level stratified by tumor location. Cox proportional hazards model was used to assess a statistical interaction between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. A statistically significant interaction was found between LINE 1 methylation level and tumor location in colorectal cancer-specific mortality analysis (Pinteraction = 0.011). The association of LINE-1 hypomethylation with higher colorectal cancer-specific mortality was stronger in proximal colon cancers (multivariable hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.21 to 2.28) than in distal colon cancers (multivariable HR, 1.18; 95% CI, 0.81 to 1.72) or rectal cancers (multivariable HR, 0.87; 95% CI, 0.57 to 1.34). Our data suggest the interactive effect of LINE-1 methylation level and colorectal cancer location on clinical outcome. PMID- 27391154 TI - Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo. AB - AIMS: Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2alpha (AP-2alpha) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. METHODS AND RESULTS: In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2alpha reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2alpha phosphorylation and its activity, upregulated IkBalpha mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2alpha completely abolished aspirin-induced upregulation of IkBalpha levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2alpha phosphorylation and IkBalpha protein expression in humans subjects. CONCLUSION: Aspirin activates AP-2alpha to upregulate IkBalpha gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID- 27391157 TI - MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma. AB - The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway is frequently hyper-activated upon vemurafenib treatment of melanoma. We have here investigated the relationship between SRY-box 10 (SOX10), forkhead box 3 (FOXD3) and microphthalmia-associated transcription factor (MITF) in the regulation of the receptor tyrosine-protein kinase ERBB3, and its cognate ligand neuregulin 1-beta (NRG1-beta). We found that both NRG1-beta and ERBB3 mRNA levels were elevated as a consequence of MITF depletion, induced by either vemurafenib or MITF small interfering RNA (siRNA) treatment. Elevation of ERBB3 receptor expression after MITF depletion caused increased activation of the PI3K pathway in the presence of NRG1-beta ligand. Together, our results suggest that MITF may play a role in the development of acquired drug resistance through hyper-activation of the PI3K pathway. PMID- 27391155 TI - Induction of apoptosis and autophagy via mitochondria- and PI3K/Akt/mTOR-mediated pathways by E. adenophorum in hepatocytes of saanen goat. AB - E. adenophorum has reported to cause hepatotoxicity. But, the precise effects of E. adenophorum on hepatocytes is unclear. Saanen goats were fed on E. adenophorum to detect the cytotoxicity effects of E. adenophorum on hepatocytes. Our study has shown that the typical apoptotic features, the increasing apoptotic hepatocytes and activated caspase-9, -3 and the subsequent cleavage of PARP indicated the potent pro-apoptotic effects of E. adenophorum. Moreover, the translocation of Bax and Cyt c between mitochondria and cytosol triggering the forming of apoptosome proved that the mitochondria-mediated apoptosis was triggered by E. adenophorum. Furthermore, E. adenophorum increased the MDC positive autophagic vacuoles and the subcellular localization of punctate LC3, the ratio of LC3-II/LC3-I and the protein levels of Beclin 1, but decreased that of P62, indicating the potent pro-autophagic effects of E. adenophorum. In addition, E. adenophorum significantly inhibited the protein leves of p-PI3K, p Akt and p-mTORC1, but increased PTEN and p-AMPK. Also, the p-mTORC2 and p-Akt Ser473 were inhibited, indicating that the supression of mTORC2/Akt pathway could induce the autophagy of hepatocytes. The autophagy-realted results indicated that the inhibition of PI3K/Akt/mTORC1- and mTORC2/Akt-mediated pathways contributed to the pro-autophagic activity of E. adenophorum. These findings provide new insights to understand the mechanisms involved in E. adenophorum-caused hepatotoxicity of Saanen goat. PMID- 27391158 TI - Concurrent paclitaxel/cisplatin chemoradiotherapy with or without consolidation chemotherapy in high-risk early-stage cervical cancer patients following radical hysterectomy: preliminary results of a phase III randomized study. AB - A phase III randomized study on the efficacy and safety of consolidation chemotherapy with paclitaxel plus cisplatin following radical hysterectomy and adjuvant chemoradiotherapy (CRT) in the treatment of high risk early-stage cervical cancer were reported. 146 eligible patients were randomized to arm A receiving concurrent CRT or arm B receiving CRT plus consolidation chemotherapy, respectively. An interim analysis showed a trend of improvement on disease-free survival (DFS) and overall survival (OS) in arm B with hazard ratios (HR) of 1.25 (95% CI = 0.60-2.60, p = 0.55) and 1.43 (95% CI = 0.64-3.20, p = 0.38) for DFS and OS, respectively. The 3-year DFS and OS were 82.0% vs.74.3%, and 86.6% vs. 78.3% for patients receiving CRT plus consolidation chemotherapy and CRT alone, respectively. There was significant difference between the two arms in distant alone recurrence (p = 0.048). Multivariate analysis indicated that pathologic type was a significant prognostic factor for OS (p = 0.045), positive pelvic nodes were significantly associated with both OS ( p=0.02) and DFS (P=0.03). Grade 2 to 4 gastrointestinal disorder (p = 0.95), radiation enteritis (P=0.48), radiation cystitis (p = 0.27) and radioepidermitis (p = 0.46) were similar in the two arms. Overall rates of grade 0-2/3-4 myelosuppression were 87.7%/12.3% for arm A and 74.6%/25.4% for arm B, respectively, but this difference was not statistically significant (p = 0.05). In conclusion, concurrent CRT plus consolidation chemotherapy may play a potential role in further improving survival outcomes for high-risk early stage cervical cancer patients compared CRT alone. PMID- 27391160 TI - Smoking Cessation and the Microbiome in Induced Sputum Samples from Cigarette Smoking Asthma Patients. AB - Asthma is a common disease causing cough, wheezing and shortness of breath. It has been shown that the lung microbiota in asthma patients is different from the lung microbiota in healthy controls suggesting that a connection between asthma and the lung microbiome exists. Individuals with asthma who are also tobacco smokers experience more severe asthma symptoms and smoking cessation is associated with improved asthma control. In the present study we investigated if smoking cessation in asthma patients is associated with a change in the bacterial community in the lungs, examined using induced sputum. We found that while tobacco smokers with asthma have a greater bacterial diversity in the induced sputum compared to non-smoking healthy controls, smoking cessation does not lead to a change in the microbial diversity. PMID- 27391161 TI - Layer Control of WSe2 via Selective Surface Layer Oxidation. AB - We report Raman and photoluminescence spectra of mono- and few-layer WSe2 and MoSe2 taken before and after exposure to a remote oxygen plasma. For bilayer and trilayer WSe2, we observe an increase in the photoluminescence intensity and a blue shift of the photoluminescence peak positions after oxygen plasma treatment. The photoluminescence spectra of trilayer WSe2 exhibit features of a bilayer after oxygen plasma treatment. Bilayer WSe2 exhibits features of a monolayer, and the photoluminescence of monolayer WSe2 is completely absent after the oxygen plasma treatment. These changes are observed consistently in more than 20 flakes. The mechanism of the changes observed in the photoluminescence spectra of WSe2 is due to the selective oxidation of the topmost layer. As a result, N-layer WSe2 is reduced to N-1 layers. Raman spectra and AFM images taken from the WSe2 flakes before and after the oxygen treatment corroborate these findings. Because of the low kinetic energy of the oxygen radicals in the remote oxygen plasma, the oxidation is self-limiting. By varying the process duration from 1 to 10 min, we confirmed that the oxidation will only affect the topmost layer of the WSe2 flakes. X-ray photoelectron spectroscopy shows that the surface layer WOx of the sample can be removed by a quick dip in KOH solution. Therefore, this technique provides a promising way of controlling the thickness of WSe2 layer by layer. PMID- 27391159 TI - Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion. AB - The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells.Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin's effects in elevating intracellular superoxide (O2.-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2.-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2.- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2.- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ZnSOD restored intracellular O2.- levels and rescued invasive capacity.Our study therefore identified gelsolin as a novel regulator of intracellular O2.- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu. PMID- 27391162 TI - Weight Change and Associated Factors in Long-Term Breast Cancer Survivors. AB - PURPOSE: Weight gain often occurs after breast cancer diagnosis and significantly impacts the general health of cancer survivors. While the number of breast cancer survivors is increasing, few studies have reported data on weight change beyond 5 years post-diagnosis. We investigated weight change and associated factors in long-term survivors of breast cancer. PATIENTS AND METHODS: Medical records were reviewed on 1363 breast cancer patients and a total of 822 women who had survived beyond 5 years since diagnosis were included in the final analysis. The association between demographic, anthropometric, lifestyle, cancer related factors (including time since diagnosis, treatment modality, pathologic stage, and hormone receptor status), and weight-change over 5 years were examined. RESULTS: During an average 8.2 years of follow-up time, mean weight gain was 0.32kg (p = 0.017). 175 (21.3%) patients had gained more than 5% of their weight at diagnosis and their average gain was 5.55kg. Body mass index (BMI) at diagnosis, age at diagnosis, aromatase inhibitor (AI) use, heavy drinking, and type of surgery were associated with relative weight gain (>=5%) in univariate analysis (all p-values<0.05). Patients who were non-obese at diagnosis showed weight gain, while those who were obese at diagnosis lost weight (0.78kg,-1.11kg, respectively, p<0.001). In multivariate analysis, the non-obese group showed odds ratio of 2.7 (p = 0.001) relative to the obese group. Younger age group (age 18 54 years) showed odds ratio of 1.9 (p = 0.021) relative to the older age group (age 55-75 years), and patients who did not use AI showed odds ratio of 2.2 (p = 0.006) relative to women who did. CONCLUSION: Long-term breast cancer survivors who were non-obese at diagnosis are more likely to gain weight than obese survivors. Younger survivors and survivors who have never used AI are also likely to gain weight. PMID- 27391163 TI - Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues. AB - Carcinogenesis is a complex multifactorial, multistage process, but the precise mechanisms are not well understood. In this study, we performed a genome-wide analysis of the copy number variation (CNV), breakpoint region (BPR) and fragile sites in 2,737 tumor samples from eight tumor entities and in 432 normal samples. CNV detection and BPR identification revealed that BPRs tended to accumulate in specific genomic regions in tumor samples whereas being dispersed genome-wide in the normal samples. Hotspots were observed, at which segments with similar alteration in copy number were overlapped along with BPRs adjacently clustered. Evaluation of BPR occurrence frequency showed that at least one was detected in about and more than 15% of samples for each tumor entity while BPRs were maximal in 12% of the normal samples. 127 of 2,716 tumor-relevant BPRs (termed 'common BPRs') exhibited also a noticeable occurrence frequency in the normal samples. Colocalization assessment identified 20,077 CNV-affecting genes and 169 of these being known tumor-related genes. The most noteworthy genes are KIAA0513 important for immunologic, synaptic and apoptotic signal pathways, intergenic non-coding RNA RP11-115C21.2 possibly acting as oncogene or tumor suppressor by changing the structure of chromatin, and ADAM32 likely importance in cancer cell proliferation and progression by ectodomain-shedding of diverse growth factors, and the well known tumor suppressor gene p53. The BPR distributions indicate that CNV mutations are likely non-random in tumor genomes. The marked recurrence of BPRs at specific regions supports common progression mechanisms in tumors. The presence of hotspots together with common BPRs, despite its small group size, imply a relation between fragile sites and cancer-gene alteration. Our data further suggest that both protein-coding and non-coding genes possessing a range of biological functions might play a causative or functional role in tumor biology. This research enhances our understanding of the mechanisms for tumorigenesis and progression. PMID- 27391164 TI - Correction: RNA-Seq Reveals the Angiogenesis Diversity between the Fetal and Adults Bone Mesenchyme Stem Cell. AB - [This corrects the article DOI: 10.1371/journal.pone.0149171.]. PMID- 27391165 TI - Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters. AB - BACKGROUND AND PURPOSE: 4-Methyl-N-methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate-type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5-HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N-demethylated metabolite, 4-methylcathinone (nor-mephedrone); the ring-hydroxylated metabolite, 4-hydroxytolylmephedrone (4-OH-mephedrone); and the reduced keto-metabolite, dihydromephedrone. EXPERIMENTAL APPROACH: We used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3 mg.kg(-1) ) on extracellular dopamine and 5-HT levels in rat nucleus accumbens. KEY RESULTS: In cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor mephedrone and 4-OH-mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor mephedrone produced elevations in extracellular dopamine and 5-HT, whereas 4-OH mephedrone did not. Mephedrone and nor-mephedrone, but not 4-OH-mephedrone, induced locomotor activity. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor-mephedrone increases extracellular dopamine and 5 HT in the brain whereas 4-OH-mephedrone does not, suggesting the latter metabolite does not penetrate the blood-brain barrier. Future studies should examine the pharmacokinetics of nor-mephedrone to determine its possible contribution to the in vivo effects produced by mephedrone. PMID- 27391166 TI - Substrate-mediated commitment of human embryonic stem cells for hepatic differentiation. AB - Human embryonic stem cell (hESC)-derived endodermal cells are of interest for the development of cellular therapies to treat disorders such as liver failure. The soluble form of activin A (Act) has been widely used as an in vitro inducer of definitive endoderm (DE). In this study, we have developed a nanofibrous poly (E caprolactone) substrate, biofunctionalized with Act, for directed differentiation of hESCs into DE. Bioconjugation of Act on nanofibrous meshes was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunostaining. In order to investigate the bioactivity of immobilized Act (iAct), hESCs were cultivated on the Act-conjugated nanofibers for five days. The nanofibers with covalent iAct significantly increased expression levels of the endodermal markers SOX17, FOXA2, and CXCR4, compared with physically adsorbed Act (aAct) or without Act (noAct). In addition, iAct retained its bioactivity after storage for five days in the absence of cell seeding. The capability of cultivated cells to generate the DE derived lineage was evaluated through further differentiation of seeded cells into hepatocyte-like cells (HLCs). Interestingly, the iAct sample showed a higher level of hepatic markers compared to the aAct sample. We also demonstrated that iAct in the presence of soluble Act (sAct) could improve the conventional protocol to generate HLCs from hESCs. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2861-2872, 2016. PMID- 27391167 TI - John Cunningham (JC) virus genotypes in kidney transplant recipients, rheumatoid arthritis patients and healthy individuals in Isfahan, Iran. AB - In healthy individuals John Cunningham virus is latent without any clinical signs, but in the cases of the use of immunosuppressive drugs in graft recipients, autoimmune diseases and also increasing of age, that the immune system is suppressed it may cause disease in reactivation. Progressive multifocal leukoencephalopathy (PML) is the well-known disease caused by the virus. It has also been associated with nephropathy and tumorogensis. At present, based on vp1 capsid gene 7 genotypes have been detected. Genetic variations of JC virus in different geographical areas and the presence of different subtypes is a useful tool for reconstructing of the genetic information of JC virus and understanding of its evolution. The aim of this study was to investigate different genotypes of the JC virus in the urine of 100 kidney transplant recipients, 43 rheumatoid arthritis patients, and 100 healthy individuals as control group in Isfahan. DNA was extracted by phenol-chloroform method and subjected to a nested PCR using specific primer for vp1 capsid gene designed by Oligo 7 software. Fisher's exact test was used for statistical analyses. Using MEGA 6 software the sequences were aligned using Clustal W tool and phylogenetic trees were constructed by neighbor joining method. Thirty-one positive samples were sequenced. Genotypes 1, 3, and 4 of the virus were detected for the first time in Iran. For the first time genotype 3 was reported as the dominant genotype in Iran. For the first time in the world, genotype 4 was detected in rheumatoid arthritis patients. J. Med. Virol. 89:337-344, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27391168 TI - Factors influencing inter-day glycemic variability in diabetic outpatients receiving insulin therapy. AB - INTRODUCTION: The aim of the present study was to determine the actual state of inter-day glycemic variability and identify the factors that affect glycemic variability in diabetic outpatients on insulin therapy. MATERIALS AND METHODS: The participants were 45 outpatients with diabetes mellitus receiving insulin therapy. The mean plasma glucose (MPG) levels, intra-day glycemic variability (expressed by standard deviation and mean amplitude of glucose excursion) and inter-day glycemic variability (expressed by mean of daily differences [MODD] in blood glucose levels) were measured continuously over 7 days with iPro2(r) . The primary outcome was the relationship between MODD and the life variability index. RESULTS: MODD values were high in 93.3% of the participants, and significantly higher in patients with lifestyle changes than in those without (higher in patients with high life variability index). MODD values were not associated with age, but significantly higher in women. MODD values correlated significantly with glycated hemoglobin and glycoalbumin levels, and negatively with 1,5 anhydroglucitol levels. MODD values were significantly higher in type 1 diabetes patients and not associated with duration of disease. MODD values correlated significantly with insulin dose. Multivariate analysis identified the life variability index as a significant determinant of MODD. CONCLUSIONS: iPro2(r) provided detailed information on glycemic profile in diabetic outpatients receiving insulin therapy. The results suggest that patients with large inter-day glycemic variability are unlikely to achieve an improvement in their glycated hemoglobin level. Treatment and instructions based on a patient's characteristics, day-to-day glycemic variability and lifestyle are important to achieve good glycemic control. PMID- 27391169 TI - Girls' and boys' experience with teen sexting in early and late adolescence. AB - This study explored the extent to which sexting represents a problematic behavior in early and late adolescence. Using data from the EU Kids Online II project (17,016 participants aged 11-16 from 25 European countries, 49.7% boys), multilevel logistic regression analyses were conducted separately for four groups: younger girls, older girls, younger boys, and older boys. Irrespective of age and gender, sexting was associated with emotional problems and alcohol use. Its effect decreased in older adolescents, except for emotional difficulties, which remained relatively high in older boys. Vaginal sex was associated with sexting in both younger and older boys while, in girls, the association was observed only in the older group. Younger boys with higher self-efficacy were more likely to send sexts than those with lower self-efficacy. Although sexting is associated with psychological challenges and other types of risk behavior, sexting in some younger boys may not necessarily represent problematic behavior. PMID- 27391170 TI - Clinical and microbiological characteristics associated with mortality in spontaneous bacterial peritonitis: a multicenter cohort study. AB - OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a prevalent and high mortality complication of cirrhosis. We aimed to describe these patients' clinical and microbiological characteristics and evaluate their impact on outcomes. METHODS: This was a retrospective cohort study including 139 consecutive patients with positive culture SBP from three Portuguese centers diagnosed between 2009 and 2014. Multivariate logistic regression was used to study associations with 30-day mortality. RESULTS: The mean age of the patients was 62 years and 81% of patients were men. The mean model for end-stage liver disease score was 19. Hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding developed in 47, 30, and 21% of patients, respectively. Gram-positive bacteria were isolated in the ascitic fluid of 42% of patients. Resistance to quinolones and multiresistance were found in 33 and 17% of patients, respectively. C-reactive protein level (adjusted odds ratio, 1.16 per 1 mg/l increment) and development of hepatorenal syndrome (adjusted odds ratio, 2.86) were associated independently with 30-day mortality (model's area under the curve, 0.78). CONCLUSION: In this cohort, SBP portended high early mortality. Gram-positive bacteria, bacteria resistant to quinolones, and multiresistant bacteria were identified in considerable proportions of patients. In the setting of the high early mortality and changing microbiological profile, SBP management strategies need to be improved. PMID- 27391171 TI - Clinical predictors of Crohn's disease course. AB - A modern approach to Crohn's disease (CD) should be influenced by the patient's underlying prognosis. Here, I analyse the clinical factors predicting CD course on the basis of information obtained at diagnosis and in the year following diagnosis. Perianal disease at diagnosis appears to be a strong predictor of unfavourable outcome and has been associated with a more frequent use of immunosuppressive treatment. Early age at diagnosis, ileocolonic disease and extraintestinal manifestations are characteristics of patients at risk for more complicated disease. Otherwise, patients subjected to surgery at diagnosis or during the first year of follow-up appear to have a relatively benign outcome. Disease activity in the year after diagnosis appears to be a good predictor of future disease activity as about two-third of the patients who remain in remission tend to remain unchanged thereafter, whereas those patients treated with steroids have, manifestly, an unfavourable subsequent clinical course. Moreover, there is consistent evidence that active smoking is associated with a complicated disease course. The results of the studies reviewed suggest that the combination of 'phenotype at diagnosis' and 'comportment follow-up classification' in the year following diagnosis can be potentially useful prognostic factors in clinical practice. With the development of newer therapies in CD, there is a growing need to predict disease outcome, despite the difficult challenge in anticipating the future clinical course in a given patient. PMID- 27391174 TI - Climate adaptation is not enough: warming does not facilitate success of southern tundra plant populations in the high Arctic. AB - Rapidly rising temperatures are expected to cause latitudinal and elevational range shifts as species track their optimal climate north and upward. However, a lack of adaptation to environmental conditions other than climate - for example photoperiod, biotic interactions, or edaphic conditions - might limit the success of immigrants in a new location despite hospitable climatic conditions. Here, we present one of the first direct experimental tests of the hypothesis that warmer temperatures at northern latitudes will confer a fitness advantage to southern immigrants relative to native populations. As rates of warming in the Arctic are more than double the global average, understanding the impacts of warming in Arctic ecosystems is especially urgent. We established experimentally warmed and nonwarmed common garden plots at Alexandra Fiord, Ellesmere Island in the Canadian High Arctic with seeds of two forb species (Oxyria digyna and Papaver radicatum) originating from three to five populations at different latitudes across the Arctic. We found that plants from the local populations generally had higher survival and obtained a greater maximum size than foreign individuals, regardless of warming treatment. Phenological traits varied with latitude of the source population, such that southern populations demonstrated substantially delayed leaf-out and senescence relative to northern populations. Our results suggest that environmental conditions other than temperature may influence the ability of foreign populations and species to establish at more northerly latitudes as the climate warms, potentially leading to lags in northward range shifts for some species. PMID- 27391173 TI - Structure of the magnetosome-associated actin-like MamK filament at subnanometer resolution. AB - Magnetotactic bacteria possess cellular compartments called magnetosomes that sense magnetic fields. Alignment of magnetosomes in the bacterial cell is necessary for their function, and this is achieved through anchoring of magnetosomes to filaments composed of the protein MamK. MamK is an actin homolog that polymerizes upon ATP binding. Here, we report the structure of the MamK filament at ~6.5 A, obtained by cryo-Electron Microscopy. This structure confirms our previously reported double-stranded, nonstaggered architecture, and reveals the molecular basis for filament formation. While MamK is closest in sequence to the bacterial actin MreB, the longitudinal contacts along each MamK strand most closely resemble those of eukaryotic actin. In contrast, the cross-strand interface, with a surprisingly limited set of contacts, is novel among actin homologs and gives rise to the nonstaggered architecture. PMID- 27391172 TI - A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice. AB - Most US Food and Drug Administration (FDA)-approved treatments for osteoporosis target osteoclastic bone resorption. Only PTH derivatives improve bone formation, but they have drawbacks, and novel bone-anabolic agents are needed. Nitrates, which generate NO, improved BMD in estrogen-deficient rats and may improve bone formation markers and BMD in postmenopausal women. However, nitrates are limited by induction of oxidative stress and development of tolerance, and may increase cardiovascular mortality after long-term use. Here we studied nitrosyl-cobinamide (NO-Cbi), a novel, direct NO-releasing agent, in a mouse model of estrogen deficiency-induced osteoporosis. In murine primary osteoblasts, NO-Cbi increased intracellular cGMP, Wnt/beta-catenin signaling, proliferation, and osteoblastic gene expression, and protected cells from apoptosis. Correspondingly, in intact and ovariectomized (OVX) female C57Bl/6 mice, NO-Cbi increased serum cGMP concentrations, bone formation, and osteoblastic gene expression, and in OVX mice, it prevented osteocyte apoptosis. NO-Cbi reduced osteoclasts in intact mice and prevented the known increase in osteoclasts in OVX mice, partially through a reduction in the RANKL/osteoprotegerin gene expression ratio, which regulates osteoclast differentiation, and partially through direct inhibition of osteoclast differentiation, observed in vitro in the presence of excess RANKL. The positive NO effects in osteoblasts were mediated by cGMP/protein kinase G (PKG), but some of the osteoclast-inhibitory effects appeared to be cGMP-independent. NO-Cbi increased trabecular bone mass in both intact and OVX mice, consistent with its in vitro effects on osteoblasts and osteoclasts. NO-Cbi is a novel direct NO releasing agent that, in contrast to nitrates, does not generate oxygen radicals, and combines anabolic and antiresorptive effects in bone, making it an excellent candidate for treating osteoporosis. (c) 2016 American Society for Bone and Mineral Research. PMID- 27391175 TI - Appy Hour: Health Sciences Professionals Learn About Apps. AB - Appy Hour is a recurring event hosted by an academic health sciences library featuring apps that are informally presented and demonstrated by invited speakers. The audience is encouraged to ask questions during the presentation of the featured app(s). This event provides learning and networking opportunities for health sciences faculty, staff, students, and health care professionals. This article illustrates the process for hosting the event, shares lessons learned, and discusses possible future directions to gain a wider audience. PMID- 27391176 TI - The Impact of Library Resources and Services on the Scholarly Activity of Medical Faculty and Residents. AB - Librarians at an academic medical center library gathered data to determine if library services and resources impacted scholarly activity. A survey was developed and sent out to faculty and residents asking how they used the library during scholarly activity. Sixty-five faculty members and residents responded to the survey. The majority of respondents involved with scholarly activity use the library's services and resources. PubMed is the most frequently used database. The positive results show the library impacts the scholarly activity of medical faculty and residents. PMID- 27391177 TI - Starting a Fee-Based Systematic Review Service. AB - The George T. Harrell Health Sciences Library at Penn State College of Medicine began a fee-based systematic review service, a model for cost recovery, in October 2013. This article describes the library's experience in establishing, introducing, and promoting the new service, which follows the Institute of Medicine's recommended standards for performing systematic reviews. The goal is to share this information with librarians who are contemplating starting such a service. PMID- 27391178 TI - Play It, Learn It, Make It Last: Developing an Online Game to Create Self Sufficient Library Information Users. AB - Library orientation at an academic health sciences library consisted of a five minute overview within new student orientation. Past experience indicated this brief presentation was insufficient for students to learn about library resources. In 2014, an effort was made to supplement orientation by developing an online game aimed at enabling students to become self-sufficient through hands-on learning. A gaming model was chosen with expectations that competition and rewards would motivate students. Although the pilots suffered from low participation rates, the experience merits further research into the potential of a broader model of online library instruction in the health sciences environment. PMID- 27391179 TI - Assessment of Service Desk Quality at an Academic Health Sciences Library. AB - Due to an identified need for formal assessment, a small team of librarians designed and administered a survey to gauge the quality of customer service at their academic health sciences library. Though results did not drive major changes to services, several important improvements were implemented and a process was established to serve as a foundation for future use. This article details the assessment process used and lessons learned during the project. PMID- 27391180 TI - Content Analysis of Virtual Reference Data: Reshaping Library Website Design. AB - An academic health sciences library wanted to redesign its website to provide better access to health information in the community. Virtual reference data were used to provide information about user searching behavior. This study analyzed three years (2012-2014) of virtual reference data, including e-mail questions, text messaging, and live chat transcripts, to evaluate the library website for redesigning, especially in areas such as the home page, patrons' terminology, and issues prompting patrons to ask for help. A coding system based on information links in the current library website was created to analyze the data. PMID- 27391181 TI - A Journey Worth Taking: Exploring a Hybrid Embedded Library Instruction Model Through Three Distinct Cases. AB - To facilitate systematic learning and to complement the limitations of conventional one-shot library instruction sessions, a hybrid embedded instruction model was designed and implemented for undergraduate students and residents in three disciplines at the University of Oklahoma Health Sciences Center. Variations of hybrid instruction are explored, including models that combine face to-face interactions, online content delivery, flipped instruction techniques, and individual consultations. The hybrid model highlights benefits of collaborative teaching between course faculty members and librarians and enhances the relevance of library instruction for users. PMID- 27391182 TI - SAGE Research Methods Datasets: A Data Analysis Educational Tool. AB - SAGE Research Methods Datasets (SRMD) is an educational tool designed to offer users the opportunity to obtain hands-on experience with data analysis. Users can search for and browse authentic datasets by method, discipline, and data type. Each of the datasets are supplemented with educational material on the research method and clear guidelines for how to approach data analysis. PMID- 27391183 TI - Smart Buildings: An Introduction to the Library of the Future. AB - Advances in building technologies are combining energy efficiency, networked sensors, and data recording in exciting ways. Modern facilities can adjust lighting, heating, and cooling outputs to maximize efficiency, provide better physical security, improve wayfinding for occupants, and provide detailed reports of building use. This column will briefly explore the idea of "smart buildings," describe some of the technologies that are being developed for these buildings, and explore their implications for libraries. A brief listing of selected smart building technologies is also provided. PMID- 27391184 TI - Honoring Our Hospital's History: A Preservation and Digitization Initiative. AB - There is limited literature on hospital archives projects. Hospitals understandably have a strong focus on patient care, but there is still a critical need to keep institutional archives. Among their many uses, institutional archives preserve corporate memory, provide evidence of interactions with community, and assist in contemporary decision making. This column describes a university-hospital partnership to undertake a one-year project to preserve, detail, and digitize ten boxes, or approximately 3.8 meters, of materials dating from 1980 to 2006. This project serves as a model for other hospital or health care facilities wanting to preserve and more actively engage with their archival collections. PMID- 27391185 TI - Expanding Library Services and Instruction Through LibGuides. AB - Beginning in 2012, the Charles R. Drew University (CDU) Health Sciences Library used LibGuides in a number of innovative ways. Librarians constructed e-book databases, in-depth tutorials on technology-related topics, and web pages highlighting special events. To assess similar LibGuides innovation, CDU librarians developed an eight-question survey distributed to health sciences and hospital libraries throughout Southern California and Arizona. Results showed that libraries used LibGuides primarily to deliver access to online resources and to provide supplementary materials supporting instruction. Responses also revealed that many libraries had not yet adopted LibGuides. These findings were analyzed and compared to past and current LibGuides design at CDU. PMID- 27391191 TI - Pathological fracture due to lytic lesion caused by a myeloid neoplasm with FIP1L1-PDGFRA. PMID- 27391192 TI - Gold-Catalyzed Povarov-Type Reaction of Fluorinated Imino Esters and Furans. AB - A gold-catalyzed Povarov-type reaction of fluorinated imino esters and furans is described. The process, which takes place in dichoromethane at room temperature, gives rise to novel fluorinated tetrahydrofuran-fused tetrahydroquinolines in good yields and moderate levels of diastereoselectivity in a very simple manner. The reported examples expand the versatility of the Povarov reaction to unprecedented fluorinated substrates, generating scaffolds that contain quaternary alpha-amino acid units. PMID- 27391190 TI - Sharing the Roles: An Assessment of Japanese Medaka Estrogen Receptors in Vitellogenin Induction. AB - Teleost fish express at least three estrogen receptor (ER) subtypes. To date, however, the individual role of these ER subtypes in regulating expression of estrogen responsive genes remains ambiguous. Here, we investigate putative roles of three ER subtypes in Japanese medaka (Oryzias latipes), using vitellogenin (VTG) I and II as model genes. We identify specific ligand/receptor/promoter dynamics, using transient transactivation assays that incorporate luciferase reporters comprising 3kb promoter/enhancer regions of medaka VTGI and VTGII genes. Four steroidal estrogens (17beta-estradiol, estrone, estriol, and 17alpha estradiol) were tested in these assays. Results indicate that all three medaka ERs (mERs) are capable of initiating transactivation of both VTG I and II, with ERbeta2 exhibiting greatest activity. Promoter deletion analysis suggests that ligand-specific receptor transactivation and utilization of regional-specific estrogen response elements may be associated with differential activities of each medaka ER. Further, cluster analysis of in vivo gene expression and in vitro transactivation suggests that all three ER subtypes putatively play a role in up regulation of VTG. Results illustrate that preferential ligand/receptor/promoter interactions may have direct implications for VTG gene expression and other ER mediated regulatory functions that are relevant to the risk assessment of estrogenic compounds. PMID- 27391193 TI - Sustainable professional activities. PMID- 27391194 TI - Harbingers of Long-term Graft Outcome: Go With the Flow? PMID- 27391195 TI - Histological Analysis in ABO-Compatible and ABO-Incompatible Kidney Transplantation by Performance of 3- and 12-Month Protocol Biopsies. AB - BACKGROUND: ABO-incompatible (ABO-I) kidney transplantation (KTx) is an established procedure to expand living donor sources. Although graft and patient survival rates are comparable between ABO-compatible (ABO-C) and ABO-I KTx, several studies have suggested that ABO-I KTx is associated with infection. Additionally, the histological findings and incidence of antibody-mediated rejection under desensitization with rituximab and plasmapheresis remain unclear. METHODS: We reviewed 327 patients who underwent living-donor KTx without preformed donor-specific antibodies (ABO-C, n = 226; ABO-I, n = 101). Patients who underwent ABO-I KTx received 200 mg/body of rituximab and plasmapheresis, and protocol biopsy (PB) was planned at 3 and 12 months. We compared the PB findings, cumulative incidence of acute rejection in both PBs and indication biopsies, infection, and patient and graft survivals. RESULTS: The 3- and 12-month PBs were performed in 85.0% and 79.2% of the patients, respectively. Subclinical acute rejection occurred in 6.9% and 9.9% of patients in the ABO-C and ABO-I groups at 3 months (P = 0.4) and in 12.4% and 10.1% at 12 months, respectively (P = 0.5). The cumulative incidence of acute rejection determined by both PBs and indication biopsies was 20.5% and 19.6%, respectively (P = 0.8). The degrees of microvascular inflammation and interstitial fibrosis/tubular atrophy were comparable. Polyomavirus BK nephropathy was found in 2.7% and 3.0% of patients in the ABO-C and ABO-I groups, respectively (P = 1.0). The incidence of other infections and the graft/patient survival rates were not different. CONCLUSIONS: Analyses using 3- and 12-month PBs suggested comparable allograft pathology between ABO-C and ABO-I KTx under desensitization with low-dose rituximab and plasmapheresis. PMID- 27391196 TI - BK Polyomavirus and the Transplanted Kidney: Immunopathology and Therapeutic Approaches. AB - BK polyomavirus is ubiquitous, with a seropositivity rate of over 75% in the adult population. Primary infection is thought to occur in the respiratory tract, but asymptomatic BK virus latency is established in the urothelium. In immunocompromised host, the virus can reactivate but rarely compromises kidney function except in renal grafts, where it causes a tubulointerstitial inflammatory response similar to acute rejection. Restoring host immunity against the virus is the cornerstone of treatment. This review covers the virus-intrinsic features, the posttransplant microenvironment as well as the host immune factors that underlie the pathophysiology of polyomavirus-associated nephropathy. Current and promising therapeutic approaches to treat or prevent this complication are discussed in relation to the complex immunopathology of this condition. PMID- 27391197 TI - Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation. AB - BACKGROUND: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. METHODS: Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation. RESULTS: BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a. CONCLUSIONS: Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia. PMID- 27391199 TI - It Is Not the Flicker but the Fire: Severity Matters in Viral infections After Lung Transplant. PMID- 27391198 TI - Predictive Score for Posttransplantation Outcomes. AB - BACKGROUND: Most current scoring tools to predict allograft and patient survival upon kidney transplantion are based on variables collected posttransplantation. We developed a novel score to predict posttransplant outcomes using pretransplant information including routine laboratory data available before or at the time of transplantation. METHODS: Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 15 125 hemodialysis patients who underwent first deceased transplantion. Prediction models were developed using Cox models for (a) mortality, (b) allograft loss (death censored), and (c) combined death or transplant failure. The cohort was randomly divided into a two thirds set (Nd = 10 083) for model development and a one third set (Nv = 5042) for validation. Model predictive discrimination was assessed using the index of concordance, or C statistic, which accounts for censoring in time-to-event models (a-c). We used the bootstrap method to assess model overfitting and calibration using the development dataset. RESULTS: Patients were 50 +/- 13 years of age and included 39% women, 15% African Americans, and 36% persons with diabetes. For prediction of posttransplant mortality and graft loss, 10 predictors were used (recipients' age, cause and length of end-stage renal disease, hemoglobin, albumin, selected comorbidities, race and type of insurance as well as donor age, diabetes status, extended criterion donor kidney, and number of HLA mismatches). The new model (www.TransplantScore.com) showed the overall best discrimination (C-statistics, 0.70; 95% confidence interval [95% CI], 0.67-0.73 for mortality; 0.63; 95% CI, 0.60-0.66 for graft failure; 0.63; 95% CI, 0.61-0.66 for combined outcome). CONCLUSIONS: The new prediction tool, using data available before the time of transplantation, predicts relevant clinical outcomes and may perform better to predict patients' graft survival than currently used tools. PMID- 27391200 TI - The Ethics of Penile Transplantation: Preliminary Recommendations. AB - BACKGROUND: For men with significant genitourinary injury, penile transplantation is being considered as an option when reconstruction is not feasible or proves unacceptable to the injured patient. METHODS: A review of the literature was conducted to assess the current state of penile reconstruction and transplantation options, as well as to evaluate scholarly research addressing the ethical dimensions of penile transplantation. RESULTS: The state of penile transplantation is elementary. If reconstruction is not a possibility, proceeding ethically with research on penile vascularized composite allotransplantation will require the articulation of guidelines. To date, very little has been published in the scholarly literature assessing the ethics of penile transplantation. CONCLUSIONS: Guidelines should be developed to address penile transplantation and must cover the donation of tissue, consent, subject selection, qualifications of the surgical team, and management of both failure and patient dissatisfaction. Unless guidelines are established and disseminated, penile transplants should not be undertaken. The preliminary recommendations suggested in this article may help to inform development of guidelines. PMID- 27391201 TI - The Higher Rates of Ileus, Readmission and Hernia After Laparoscopic Donor Nephrectomy Reported Can Be Mitigated by Using a Retroperitoneal Approach Via a Pfannenstiel Incision. PMID- 27391202 TI - Early Nosocomial Infections: A Large Knowledge Gap in Need of Research to Improve Outcomes. PMID- 27391203 TI - Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. AB - INTRODUCTION: Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are nucleoside reverse transcriptase inhibitors approved as pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). Prophylactic TDF-based regimens have been shown to reduce the risk of HIV infection by 74 to 92% among participants with detectable drug levels. Adverse events observed in clinical trials include nausea, elevated creatinine and liver enzymes, and decreased bone mineral density. AREAS COVERED: This article reviews the pharmacology, pharmacokinetics, and the safety profile of TDF and FTC used as PrEP for HIV infection. EXPERT OPINION: TDF-FTC can have a large impact in preventing HIV infections among high risk individuals when taken daily. Although TDF-FTC is associated with adverse events, they can be minimized with clinician-guided monitoring. PMID- 27391204 TI - Validation of the Intensive Care Unit Early Warning Dashboard: Quality Improvement Utilizing a Retrospective Case-Control Evaluation. AB - INTRODUCTION: Risk stratification with the Modified Early Warning System (MEWS) or electronic cardiac arrest trigger (eCART) has been utilized with ward patients to preemptively identify high-risk patients who might benefit from enhanced monitoring, including early intensive care unit (ICU) transfer. In-hospital mortality from cardiac arrest is ~80%, making preventative interventions an important focus area. ICUs have lower patient to nurse ratios than wards, resulting in less emphasis on the development of ICU early warning systems. MATERIALS AND METHODS: Our institution developed an early warning dashboard (EWD) identifying patients who may benefit from earlier interventions. Using the adverse outcomes of cardiac arrest, ICU mortality, and ICU readmissions, a retrospective case-control study was performed using three demographic items (age, diabetes, and morbid obesity) and 24 EWD measured items, including vital signs, laboratory values, ventilator information, and other clinical information, to validate the EWD. RESULTS: Ten statistically significant areas were identified for cardiac arrest and 13 for ICU death. Identified items included heart rate, dialysis, leukocytosis, and lactate. The ICU readmission outcome was compared to controls from both ICU patients and ward patients, and statistical significance was identified for respiratory rate >30. DISCUSSION: With several statistically significant data elements, the EWD parameters have been incorporated into advanced clinical decision algorithms to identify at-risk ICU patients. CONCLUSION: Earlier identification and treatment of organ failure in the ICU improve outcomes and the EWD can serve as a safety measure for both at-risk in house patients and also extend critical care expertise through telemedicine to smaller hospitals. PMID- 27391205 TI - A retrospective study of Class II mixed-dentition treatment. AB - OBJECTIVE: To consider the effectiveness of early treatment using one mixed dentition approach to the correction of moderate and severe Class II malocclusions. MATERIALS AND METHODS: Three groups of Class II subjects were included in this retrospective study: an early treatment (EarlyTx) group that first presented at age 7 to 9.5 years (n = 54), a late treatment (LateTx) group whose first orthodontic visit occurred between ages 12 and 15 (n = 58), and an untreated Class II (UnTx) group to assess the pretreatment comparability of the two treated groups (n = 51). Thirteen conventional cephalometric measurements were reported for each group and Class II molar severity was measured on the study casts of the EarlyTx and LateTx groups. RESULTS: Successful Class II correction was observed in approximately three quarters of both the EarlyTx group and the LateTx group at the end of treatment. EarlyTx patients had fewer permanent teeth extracted than did the LateTx patients (5.6% vs 37.9%, P < .001) and spent less time in full-bonded appliance therapy in the permanent dentition than did LateTx patients (1.7 +/- 0.8 vs 2.6 +/- 0.7years, P < .001). When supervision time is included, the EarlyTx group had longer total treatment time and averaged more visits than did the LateTx group (53.1 +/- 18. 8 vs 33.7 +/- 8.3, P < .0001). Fifty-five percent of the LateTx extraction cases involved removal of the maxillary first premolars only and were finished in a Class II molar relationship. CONCLUSION: EarlyTx comprehensive mixed-dentition treatment was an effective modality for early correction of Class II malocclusions. PMID- 27391206 TI - Facile Method to Fabricate Highly Thermally Conductive Graphite/PP Composite with Network Structures. AB - Thermally conductive polymer composites have aroused significant academic and industrial interest for several decades. Herein, we report a novel fabrication method of graphite/polypropylene (PP) composites with high thermal conductivity in which graphite flakes construct a continuous thermally conductive network. The thermal conductivity coefficient of the graphite/PP composites is markedly improved to be 5.4 W/mK at a graphite loading of 21.2 vol %. Such a great improvement of the thermal conductivity is ascribed to the occurrence of orientations of crystalline graphite flakes with large particles around PP resin particles and the formation of a perfect thermally conductive network. The model of Hashin-Shtrikman (HS) is adopted to interpret the outstanding thermally conductive property of the graphite/PP composites. This work provides a guideline for the easy fabrication of thermally conductive composites with network structures. PMID- 27391207 TI - Effect of urethral wall injection of replication-defective herpes simplex virus mediated gene transfer of kynurenine aminotransferase on urethral pressure in spinal cord-injured rats. AB - AIMS: We determined whether or not replication-defective herpes simplex virus vector-mediated kynurenine aminotransferase II (HSVrd-KAT II) suppressed the tonic activity of the urethral sphincter in spinal cord-injured (SCI) rats. METHODS: Thirty-six adult female Sprague-Dawley rats were used to produce a spinal cord injury model. One week after spinalization, HSVrd-KAT II was injected into the urethral wall of rats and another two groups of SCI rats were treated with saline and HSVrd as controls. Three weeks after viral injection, the urethral pressure profile (UPP), continuous cystometry, and gene expression in the L6-S1 spinal cords were evaluated in all three groups. RESULTS: In the HSVrd KAT II group, the maximum urethral closure pressure (Pclo.max) and maximum voiding pressure were significantly decreased (23.6-24.9% and 31.6-30.9%, respectively), in addition to an increase in voiding efficiency(48.8-76%), compared with the sham and HSVrd groups. The KAT II protein and mRNA levels were significantly increased in HSV-KAT II group compared with the HSVrd group. CONCLUSION: KAT II gene therapy effectively reduced the urethral pressure, improving detrusor-sphincter dyssynergia (DSD), and detrusor overactivity (DO), probably by blocking the N-methyl-D-aspartate receptor (NMDAr) in the L6-S1 spinal cord. Neurourol. Urodynam. 36:1046-1051, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27391208 TI - Study of the interface between Na-rich and Li-rich phases in a Na-inserted spinel Li4Ti5O12 crystal for an electrode of a sodium-ion battery. AB - Spinel lithium titanate (LTO; Li4Ti5O12) is one of the promising materials for negative electrodes of sodium-ion batteries (SIBs). The stable charge-discharge performance of SIB cells using LTO electrodes depends on the reversible Na insertion-extraction mechanism of LTO, where the spinel lattice is expanded with Na insertion, and two phases, Na-inserted LTO (Na-LTO) and Li-inserted LTO (Li LTO) phases, are generated. These phases are confirmed using X-ray diffraction (XRD), while the mechanism of the two-phase coexistence with different lattice volumes is yet unclear. Here, we investigate the detailed morphology of the coexisting Na-LTO and Li-LTO phases using in situ XRD measurements and high resolution transmission electron microscopy (TEM) observation. Na-LTO (a = 8.74 A) and Li-LTO (a = 8.36 A) phases are confirmed in both the electrochemically formed Na-inserted LTO electrode and the single-crystalline LTO thin specimen. We observed that the Na-LTO/Li-LTO interface is parallel to the (001) plane, and contains an inevitable lattice mismatch along the interface, while the expansion of the Na-LTO phase can be partially relaxed normal to the interface. We observed that the Na-LTO/Li-LTO interface has interface layers of lattice disordering with a 1-2 nm width, relaxing the lattice mismatch, as opposed to results from the previous scanning TEM observation. How the different lattice volumes at the two phase interface are relaxed should be the key issue in investigation of the mechanism of Na insertion and extraction in LTO electrodes. PMID- 27391209 TI - Baseline Residual Kidney Function and Its Ensuing Rate of Decline Interact to Predict Mortality of Peritoneal Dialysis Patients. AB - BACKGROUND: Baseline residual kidney function (RKF) and its rate of decline during follow-up are purported to be reliable outcome predictors of patients undergoing Peritoneal Dialysis (PD). The independent contribution of each of these factors has not been elucidated. METHOD: We report a multicenter, longitudinal study of 493 patients incident on PD and satisfying two conditions: a glomerular filtration rate (GFR) >=1 mL/minute and a daily diuresis >=300 mL. The main variables were the GFR (mean of urea and creatinine clearances) at PD inception and the GFR rate of decline during follow-up. The main outcome variable was patient mortality. The secondary outcome variables were: PD technique failure and risk of peritoneal infection. The statistical analysis was based on a multivariate approach, placing an emphasis on the interactions between the two main study variables. MAIN RESULTS: Baseline GFR and its rate of decline performed well as independent predictors of both patient mortality and risk of peritoneal infection. These two main study variables maintained a moderate correlation with each other (r2 = 0.12, p<0.0005), and interacted clearly, as predictors of patient mortality. A low baseline GFR followed by a fast decline portended the worst survival outcome (adjusted HR 3.84, 95%CI 1.81-8.14, p<0.0005)(Ref. baseline GFR above median plus rate of decline below median). In general, the rate of decline of RKF had a greater effect on mortality than baseline GFR, which had no detectable effect on survival when the decline of RKF was slow (HR 1.17, 95% CI 0.81-2.22, p = 0.22). Conversely, a relatively high GFR at the start of PD still carried a significant risk of mortality, when RKF declined rapidly (HR 1.89, 95% CI 1.05-3.72, p = 0.028). CONCLUSION: The risk benefit balance of an early versus late start of PD cannot be evaluated without taking into consideration the rate of decline of RKF. This circumstance may contribute to explain the controversial results observed at the time of evaluating the potential benefits of an early initiation of PD. PMID- 27391210 TI - The structure of a Trypanosoma cruzi glucose-6-phosphate dehydrogenase reveals differences from the mammalian enzyme. AB - The enzyme glucose-6-phosphate dehydrogenase from Trypanosoma cruzi (TcG6PDH) catalyses the first step of the pentose phosphate pathway (PPP) and is considered a promising target for the discovery of a new drug against Chagas diseases. In the present work, we describe the crystal structure of TcG6PDH obtained in a ternary complex with the substrate beta-d-glucose-6-phosphate (G6P) and the reduced 'catalytic' cofactor NADPH, which reveals the molecular basis of substrate and cofactor recognition. A comparison with the homologous human protein sheds light on differences in the cofactor-binding site that might be explored towards the design of new NADP(+) competitive inhibitors targeting the parasite enzyme. PMID- 27391211 TI - Catalytic Asymmetric Synthesis of Cyclopentyl beta-Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates. AB - Chiral cyclopentyl beta-amino esters are formed catalytically by [3+2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 % ee and excellent diastereocontrol. Use of beta silyl-substituted enoldiazoacetates with a chiral dirhodium catalyst and trans beta-arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen-bond association between the vinylcarbamate and the intermediate metalloenolcarbene. Reductive conversion of the protected amino esters forms highly functionalized cyclopentyl beta-amino acids and 3-aminocyclopentanones. PMID- 27391212 TI - Risk of Stroke in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention versus Optimal Medical Therapy: Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Stroke is a rare but serious adverse event associated with percutaneous coronary intervention (PCI). However, the relative risk of stroke between stable patients undergoing a direct PCI strategy and those undergoing an initial optimal medical therapy (OMT) strategy has not been established yet. This study sought to investigate if, in patients with stable coronary artery disease (SCAD), an initial strategy PCI is associated with a higher risk of stroke than a strategy based on OMT alone. METHODS: We performed a meta-analysis of 6 contemporary randomized control trials in which 5673 patients with SCAD were randomized to initial PCI or OMT. Only trials with stent utilization more than 50% were included. Study endpoint was the rate of stroke during follow up. RESULTS: Mean age of patients ranged from 60 to 65 years and stent utilization ranged from 72% to 100%. Rate of stroke was 2.0% at a weighted mean follow up of 55.3 months. On pooled analysis, the risk of stroke was similar between patients undergoing a PCI plus OMT and those receiving only OMT (2.2% vs. 1.8%, OR on fixed effect = 1.24 95%CI: 0.85-1.79). There was no heterogeneity among the studies (I2 = 0.0%, P = 0.15). On sensitivity analysis after removing each individual study the pooled effect estimate remains unchanged. CONCLUSIONS: In patients with SCAD an initial strategy based on a direct PCI is not associated with an increased risk of stroke during long-term follow up compared to an initial strategy based on OMT alone. PMID- 27391213 TI - Believing androids - fMRI activation in the right temporo-parietal junction is modulated by ascribing intentions to non-human agents. AB - Attributing mind to interaction partners has been shown to increase the social relevance we ascribe to others' actions and to modulate the amount of attention dedicated to them. However, it remains unclear how the relationship between higher-order mind attribution and lower-level attention processes is established in the brain. In this neuroimaging study, participants saw images of an anthropomorphic robot that moved its eyes left- or rightwards to signal the appearance of an upcoming stimulus in the same (valid cue) or opposite location (invalid cue). Independently, participants' beliefs about the intentionality underlying the observed eye movements were manipulated by describing the eye movements as under human control or preprogrammed. As expected, we observed a validity effect behaviorally and neurologically (increased response times and activation in the invalid vs. valid condition). More importantly, we observed that this effect was more pronounced for the condition in which the robot's behavior was believed to be controlled by a human, as opposed to be preprogrammed. This interaction effect between cue validity and belief was, however, only found at the neural level and was manifested as a significant increase of activation in bilateral anterior temporoparietal junction. PMID- 27391214 TI - Deep Whole-Genome Sequencing to Detect Mixed Infection of Mycobacterium tuberculosis. AB - Mixed infection by multiple Mycobacterium tuberculosis (MTB) strains is associated with poor treatment outcome of tuberculosis (TB). Traditional genotyping methods have been used to detect mixed infections of MTB, however, their sensitivity and resolution are limited. Deep whole-genome sequencing (WGS) has been proved highly sensitive and discriminative for studying population heterogeneity of MTB. Here, we developed a phylogenetic-based method to detect MTB mixed infections using WGS data. We collected published WGS data of 782 global MTB strains from public database. We called homogeneous and heterogeneous single nucleotide variations (SNVs) of individual strains by mapping short reads to the ancestral MTB reference genome. We constructed a phylogenomic database based on 68,639 homogeneous SNVs of 652 MTB strains. Mixed infections were determined if multiple evolutionary paths were identified by mapping the SNVs of individual samples to the phylogenomic database. By simulation, our method could specifically detect mixed infections when the sequencing depth of minor strains was as low as 1* coverage, and when the genomic distance of two mixed strains was as small as 16 SNVs. By applying our methods to all 782 samples, we detected 47 mixed infections and 45 of them were caused by locally endemic strains. The results indicate that our method is highly sensitive and discriminative for identifying mixed infections from deep WGS data of MTB isolates. PMID- 27391215 TI - A case of giant cell tumor of soft parts in a horse. AB - A 12-year-old British Warmblood mare was examined by the referring veterinarian for evaluation of a cutaneous lesion on the dorsal thorax to the right of the midline. Cytologic examination of fine-needle aspirates from the mass was supportive of a giant cell tumor of soft parts (GCTSP). Laser surgical excision and postoperative methyl aminolevulinate (MAL) photodynamic therapy (PDT) were performed. Histologic examination of the mass confirmed the cytologic diagnosis. At 8 months from surgery, no evidence of recurrence has been observed. Giant cell tumors of soft parts are rare cutaneous neoplasms, observed in several domestic species, including the horse where they commonly appear as superficial cutaneous lesions without aggressive biologic behavior. Previously classified as giant cell variant of malignant fibrous histiocytoma, these superficial tumors have now been designated as giant cell tumors of soft tissue or giant cell tumors of low malignant potential within the category of fibrohistiocytic neoplasms. PMID- 27391217 TI - Vascular Epiphyte Diversity Differs with Host Crown Zone and Diameter, but Not Orientation in a Tropical Cloud Forest. AB - Vascular epiphytes are important components of biological diversity in tropical forests. We measured the species richness and abundance of vascular epiphytes along four vertical crown zones and five horizontal orientations on 376 trees, as well as the diameter at breast height (DBH) of host trees in tropical cloud forests in Bawangling, Hainan, China. The relationship between vascular epiphyte species richness and host tree DBH was assessed using a generalized linear model. There were 1,453 vascular individual epiphytes attributed to 9 families, 24 genera and 35 species, with orchids and pteridophytes dominating. Both the species richness and abundance of epiphytes significantly differed among the four crown zones for all collections and each host tree, suggesting that vertical microhabitats contribute to the distribution of epiphytes on host trees. Neither epiphyte abundance nor species richness differed among the eastern, southern, western, and northern orientations for all host trees; however, both richness and abundance were significantly higher for epiphytes that encircled host tree trunks. This suggests that morphological and physiological characteristics of the tree, but not microclimates probably contribute to the distribution of epiphytes on host trees. Epiphyte species richness was positively correlated with tree DBH across the six host tree species studied, with increases in DBH among smaller trees resulting in larger increases in richness, while increases in DBH among larger host trees resulting in more modest increases in ephiphyte richness. Our findings contribute support for a positive relationship between epiphyte species richness and host tree DBH and provide important guidance for future surveys of epiphyte community development. PMID- 27391216 TI - Colorectal cancer health services research study protocol: the CCR-CARESS observational prospective cohort project. AB - BACKGROUND: Colorectal cancers are one of the most common forms of malignancy worldwide. But two significant areas of research less studied deserve attention: health services use and development of patient stratification risk tools for these patients. METHODS: DESIGN: a prospective multicenter cohort study with a follow up period of up to 5 years after surgical intervention. Participant centers: 22 hospitals representing six autonomous communities of Spain. Participants/Study population: Patients diagnosed with colorectal cancer that have undergone surgical intervention and have consented to participate in the study between June 2010 and December 2012. Variables collected include pre intervention background, sociodemographic parameters, hospital admission records, biological and clinical parameters, treatment information, and outcomes up to 5 years after surgical intervention. Patients completed the following questionnaires prior to surgery and in the follow up period: EuroQol-5D, EORTC QLQ-C30 (The European Organization for Research and Treatment of Cancer quality of life questionnaire) and QLQ-CR29 (module for colorectal cancer), the Duke Functional Social Support Questionnaire, the Hospital Anxiety and Depression Scale, and the Barthel Index. The main endpoints of the study are mortality, tumor recurrence, major complications, readmissions, and changes in health related quality of life at 30 days and at 1, 2, 3 and 5 years after surgical intervention. STATISTICAL ANALYSIS: In relation to the different endpoints, predictive models will be used by means of multivariate logistic models, Cox or linear mixed-effects regression models. Simulation models for the prediction of discrete events in the long term will also be used, and an economic evaluation of different treatment strategies will be performed through the use of generalized linear models. DISCUSSION: The identification of potential risk factors for adverse events may help clinicians in the clinical decision making process. Also, the follow up by 5 years of this large cohort of patients may provide useful information to answer different health services research questions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02488161 . Registration date: June 16, 2015. PMID- 27391218 TI - A concise review of common animal models for the study of limb regeneration. AB - Correct selection of an appropriate animal mode to closely mimic human extremity diseases or to exhibit desirable phenotypes of limb regeneration is the first critical step for all scientists in biomedical and regenerative researches. The commonly-used animals in limb regeneration and repairing studies, such as axolotl, mice, and rats, are discussed in the review and other models including cockroaches, dogs, and horses are also mentioned. The review weighs the general advantages, disadvantages, and precedent uses of each model in the context of limb and peripheral injury and subsequent regeneration. We hope that this review can provide the reader an overview of each model, from which to select one for their specific purpose. PMID- 27391219 TI - Unveiling (-)-Englerin A as a Modulator of L-Type Calcium Channels. AB - The voltage-dependent L-type Ca(2+) channel was identified as a macromolecular target for (-)-englerin A. This finding was reached by using an unprecedented ligand-based prediction platform and the natural product piperlongumine as a pharmacophore probe. (-)-Englerin A features high substructure dissimilarity to known ligands for voltage-dependent Ca(2+) channels, selective binding affinity for the dihydropyridine site, and potent modulation of calcium signaling in muscle cells and vascular tissue. The observed activity was rationalized at the atomic level by molecular dynamics simulations. Experimental confirmation of this hitherto unknown macromolecular target expands the bioactivity space for this natural product and corroborates the effectiveness of chemocentric computational methods for prioritizing target-based screens and identifying binding counterparts of complex natural products. PMID- 27391220 TI - Moderate- to long-term periodontal outcomes of subjects failing to complete a course of periodontal therapy. AB - BACKGROUND: The current retrospective cross-sectional study investigated 5-18 year treatment outcomes in subjects who did not complete a recommended course of periodontal therapy. METHODS: Sixty-five subjects who voluntarily discontinued therapy were recalled. The subjects' demographic data and dental history since discontinuation of periodontal treatment were collected via questionnaires. The subjects' periodontal condition, radiographic data and individual tooth-based prognosis at pre-discontinuation and recall were compared. RESULTS: A total of 229 teeth had been lost over time, mainly due to periodontal reasons. Upper and lower molars were most frequently lost. Rate of tooth loss (0.38/patient per year) was comparable to untreated patients. Deterioration in periodontal health in terms of increased percentage of sites with bleeding on probing (BOP) and sites with probing pocket depths (PPD) of 6 mm or more at re-examination was observed. Positive correlations were found between tooth loss and: (i) years since therapy discontinued; (ii) percentage of sites with PPD of 6 mm or more at pre-discontinuation; and (iii) at re-examination. Percentage of sites with PPD of 6 mm or more at recall was positively correlated with periodontal tooth loss and negatively correlated with percentage of sites without BOP. CONCLUSIONS: Patients not completing a course of periodontal therapy are at risk of further tooth loss and deterioration in periodontal conditions over time. PMID- 27391221 TI - Endotherapies for Barrett esophagus. AB - Barrett esophagus (BE) is becoming an increasingly common complication. It places patients at higher risk for esophageal adenocaricnoma. Surveillance and acid suppression has been the mainstay of treatment. Recent advances in endoscopic therapies have allowed irradication of BE and reduction in cancer risk. This article reviews the available endotherapies and their efficacy. PMID- 27391222 TI - Comparative performance of isolation methods using Preston broth, Bolton broth and their modifications for the detection of Campylobacter spp. from naturally contaminated fresh and frozen raw poultry meat. AB - The performance of different isolation methods was evaluated for the detection of Campylobacter from naturally contaminated raw poultry meat. Therefore, fresh and frozen poultry meat samples were analysed using the standard procedure (ISO 10272 1:2006), enrichment in Preston broth, and enrichment in modified Bolton broth (supplemented with (i) potassium clavulanate (C-BB), (ii) triclosan (T-BB), (iii) polymyxin B (P-BB)). The enrichment cultures were streaked onto both modified charcoal cefoperazone deoxycholate agar (mCCDA) and RAPID'Campylobacter agar (RCA). Moreover, direct plating on mCCDA and RCA was performed to quantify Campylobacter. In total, 33 out of 59 fresh retail meat samples (55.9%) were Campylobacter positive. For both fresh and frozen poultry meat samples, enrichment in Bolton broth (ISO 10272-1:2006) resulted in a higher number of positive samples than enrichment in Preston broth. Supplementation of Bolton broth with potassium clavulanate (C-BB) and triclosan (T-BB) enhanced the Campylobacter recovery from fresh poultry meat compared to non-supplemented Bolton broth, although the use of C-BB was less applicable than T-BB for Campylobacter recovery from frozen samples. Additionally, the use of RCA resulted in a higher isolation rate compared to mCCDA. The present study demonstrates the impact of culture medium on the recovery of Campylobacter from fresh and frozen naturally contaminated poultry meat samples and can support laboratories in choosing the most appropriate culturing method to detect Campylobacter. PMID- 27391224 TI - Longitudinal analysis of the lung microbiota of cynomolgous macaques during long term SHIV infection. AB - BACKGROUND: Longitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing. RESULTS: We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease. CONCLUSIONS: This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease. PMID- 27391223 TI - Clinical and demographic correlates of medication and visit adherence in a large randomized controlled trial. AB - BACKGROUND: Patient characteristics are associated with adherence, which has implications for planning clinical research or designing payment systems that reward superior outcomes. It is unclear to what extent clinician efforts to improve adherence can attenuate these associations. METHODS: To identify factors predicting visit and medication adherence in settings designed to optimize adherence, we did a retrospective analysis of participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants at 632 sites in North America, Puerto Rico, and the U.S. Virgin Islands for random assignment to antihypertensive treatment with amlodipine, chlorthalidone, or lisinopril. Site investigators reported clinic characteristics at the time they applied to participate in the study and research coordinators used standardized methods to measure patient characteristics. We defined adequate visit adherence as attending at least 80 % of scheduled visits; adequate medication adherence was defined as taking 80 % or more of the randomly assigned medication at all study visits. RESULTS: The 31,250 ALLHAT participants eligible for the visit adherence analysis attended 78.5 % of scheduled study visits; 68.9 % attended more than 80 % of scheduled visits. Clinic setting was predictive of both forms of adherence; adherence was worst at private clinics; clinics that enrolled more study participants had superior adherence. Adjusting for clinic characteristics and clinical factors, women, younger participants, Blacks and smokers were less likely to have adequate visit adherence. Among the 28,967 participants eligible for the medication adherence analysis, 21,261 (73.4 %) reported adequate medication adherence. In adjusted analyses, younger and less educated participants, Blacks, and smokers were less likely to report adequate adherence. CONCLUSIONS: Participant demographics were associated with adherence despite strenuous efforts to optimize adherence. Our results could inform decisions by researchers planning trials and policymakers designing payment systems. TRIAL REGISTRATION: NCT00000542 . Registered 27 October 1999. PMID- 27391225 TI - Multilocus genotypes and broad host-range of Enterocytozoon bieneusi in captive wildlife at zoological gardens in China. AB - BACKGROUND: Enterocytozoon bieneusi is a common opportunistic pathogen that is widely detected in humans, domestic animals and wildlife, and poses a challenge to public health. The present study was performed to evaluate the prevalence, genotypic diversity and zoonotic potential of E. bieneusi among wildlife at Chengdu and Bifengxia zoological gardens in Sichuan Province, China. RESULTS: Of the 272 fresh fecal samples harvested from 70 captive wildlife species at Chengdu Zoo (n = 198) and Bifengxia Zoo (n = 74), 21 (10.6 %) and 22 (29.7 %) tested positive for E. bieneusi by internal transcribed spacer (ITS) sequencing analysis, respectively. Specifically, genotypes D, Peru 6, CHB1, BEB6, CHS9, SC02 and SC03, and genotypes D, CHB1, SC01 and SC02 were detected in the Chengdu and Bifengxia Zoo samples, respectively. Five known genotypes (D, Peru 6, BEB6, CHS9 and CHB1) and three novel genotypes (SC01, SC02 and SC03) were clustered into the zoonotic group (group 1) and host-adapted group (group 2). Multilocus sequence typing (MLST) analysis targeting three microsatellites (MS1, MS3 and MS7) and one minisatellite (MS4) were successfully sequenced for 37, 33, 35 and 37 specimens, generating 8, 3, 11 and 15 distinct locus types, respectively. Altogether, we identified 27 multilocus genotypes (MLGs) among the E. bieneusi isolates by MLST. These data highlight the high genetic diversity of E. bieneusi among zoo wildlife. CONCLUSIONS: To our knowledge, this is the first report on the prevalence and genotypic diversity of E. bieneusi infections among captive wildlife in zoos in southwest China. Notably, we identified three novel E. bieneusi genotypes, as well as six new mammalian hosts (Asian golden cats, Tibetian blue bears, blackbucks, hog deer, Malayan sun bears and brown bears) for this organism. Moreover, the occurrence of zoonotic genotypes suggests that wildlife may act as reservoirs of E. bieneusi that can serve as a source of human microsporidiosis. The findings presented here should contribute to the control of zoonotic disease in China. PMID- 27391226 TI - GRIM19 ameliorates acute graft-versus-host disease (GVHD) by modulating Th17 and Treg cell balance through down-regulation of STAT3 and NF-AT activation. AB - BACKGROUND: T helper (Th) 17 cells are a subset of T helper cells that express interleukin (IL)-17 and initiate the inflammatory response in autoimmune diseases. Regulatory T cells (Tregs) are a subpopulation of T cells that produce forkhead box P3 (FOXP3) and inhibit the immune response. Graft versus host disease (GVHD) is a complication of allogeneic tissue transplantation, and Th17 cells and their proinflammatory activity play a central role in the pathogenesis of GVHD. Gene associated with retinoid-interferon-induced mortality (GRIM) 19, originally identified as a nuclear protein, is expressed ubiquitously in various human tissues and regulate signal transducer and activator of transcription (STAT)3 activity. METHODS: Splenoytes and bone marrow cells were transplanted into mice with GVHD. The alloresponse of T cells and GVHD clinical score was measured. Realtime-polymerase chain reaction (realtime-PCR) was used to examine mRNA level. Flow cytometry and enzyme linked immunosorbent assay (ELISA) was used to evaluate protein expression. RESULTS: A GRIM19 transgenic cell transplant inhibited Th17 cell differentiation, alloreactive T cell responses, and STAT3 expression in mice with GVHD. On the other hand, the differentiation of Tregs and STAT5 production were enhanced by GRIM19. Overall, the severity of GVHD was decreased in mice that had received GRIM19 transgenic bone marrow and spleen transplants. Transplantation from GRIM19-overexpressing cells downregulated the expression of nuclear factor of activated T cells (NFATc1) but promoted the expression of regulator of calcineurin (RCAN)3 while downregulating NFAT dependent cytokine gene expression. This complex mechanism underlies the therapeutic effect of GRIM19. CONCLUSIONS: We observed that GRIM19 can reduce Th17 cell differentiation and alloreactive T cell responses in vitro and in vivo. Additionally, GRIM19 suppressed the severity of GVHD by modulating STAT3 activity and controlling Th17 and Treg cell differentiation. These results suggest that GRIM19 attenuates acute GVHD through the inhibition of the excessive inflammatory response mediated by T cell activation. PMID- 27391227 TI - Management of Candida guilliermondii joint infection in a dog. AB - BACKGROUND: Candida spp. are dimorphic fungi in the family Cryptococcaceae. Infections with Candida spp. are usually rare conditions in dogs, but immunocompromised patients have a higher risk for developing invasive candidal infections. CASE PRESENTATION: A 5-year-old male Boxer, positive to Leishmania infantum, was referred to the Veterinary Teaching Hospital of the Department of Veterinary Medicine, University of Perugia, Italy for examination of a non-weight bearing left hind limb lameness of a duration of at least 3 months. During this period, treatment involved systemic anti-inflammatory medications and intra articular corticosteroid administration. On presentation, clinical examination and radiographic findings were suggestive of cranial cruciate ligament deficiency. To support this diagnosis a stifle arthroscopy was performed: it confirmed a partial rupture of cranial cruciate ligament. Samples culture of synovial fluid and membrane was routinely collected as well, and revealed Candida guilliermondii joint infection. Treatment for the C. guilliermondii joint infection involved systemic anti-fungal therapy, joint lavage and intra-articular administration of antifungal drugs. Lameness improved markedly during this treatment, but lameness did not resolve completely, probably due to cranial cruciate ligament deficiency. Tibial tuberosity advancement (TTA) was chosen in order to treat stifle instability and was performed 4 weeks following cessation of treatment of the C. guilliermondii joint infection. Six month after TTA the dog showed a completely recovery with no lameness. CONCLUSIONS: To the authors' knowledge, this is the first case of Candida spp. joint infection reported in dogs. The cause of the progression of the joint C. guilliermondii infection remains unclear but it may be associated with leishmaniasis or intra-articular corticosteroid injections. Treatment with systemic and intra-articular anti fungal therapies was successful. In the evaluation of hind limb lameness in a chronically immunocompromised dog, it would be advisable to consider also an intra-articular Candida spp. PMID- 27391229 TI - A positive Real-Time Elastography (RTE) combined with a Prostate Cancer Gene 3 (PCA3) score above 35 convey a high probability of intermediate- or high-risk prostate cancer in patient admitted for primary prostate biopsy. AB - BACKGROUND: The standard of care in patients with suspected prostate cancer (PCa) is systematic prostate biopsies. This approach leads to unnecessary biopsies in patients without PCa and also to the detection of clinical insignificant PCa. Better tools are wanted. We have evaluated the performance of real-time elastography (RTE) combined with prostate cancer gene 3 (PCA3) in an initial biopsy setting with the goal of better identifying patients in need of prostate biopsies. METHODS: 127 patients were included in this study; three were excluded because of not measureable PCA3 score leading to 124 evaluable patients. A cut off value of 35 was used for PCA3. All patients were examined with a Hitachi Preirus with an endfire probe for RTE, a maximum of five targeted biopsies were obtained from suspicious lesions detected by RTE. All patients then had a 10-core systematic biopsy performed by another urologist unaware of the RTE results. The study includes follow-up data for a minimum of three years; all available histopathological data are included in the analysis. RESULTS: There was a significant difference in PCA3 score: 26.6 for benign disease, 73.6 for cancer patients (p < 0.001). 70 patients (56 %) were diagnosed with prostate cancer in the study period, 21 (30 %) low-risk, 32 (46 %) intermediate-risk and 17 (24 %) high-risk. RTE and PCA3 were significant markers for predicting intermediate- and high-risk PCa (p = 0.001). The combination of RTE and PCA3 had a sensitivity of 96 % and a negative predictive value (NPV) of 90 % for the group of intermediate- and high-risk PCa together and a NPV for high-risk PCa of 100 %. If both parameters are positive there is a high probability of detecting intermediate- or high-risk PCa, if both parameters are negative there is only a small chance of missing prostate cancer with documented treatment benefit. CONCLUSIONS: RTE and PCA3 may be used as pre-biopsy examinations to reduce the number of prostate biopsies. PMID- 27391230 TI - Adipo/cytokines in atherosclerotic secretomes: increased visfatin levels in unstable carotid plaque. AB - BACKGROUND: Novel pro-inflammatory and anti-inflammatory derivatives from adipose tissue, known as adipokines, act as metabolic factors. The aim of this study was to analyse the secreted expression of different adipo/cytokines in secretomes of unstable carotid atherosclerotic plaque versus non-atherosclerotic mammary artery. METHODS: We evaluated the secretion levels of adiponectin, visfatin, lipocalin-2, resistin, IL-6 and TNFR2 by ELISA in human secretomes from cultured unstable carotid atherosclerotic plaque (n = 18) and non-atherosclerotic mammary artery (n = 13). We also measured visfatin serum levels in patients suffering from atherosclerosis and in a serum cohort of healthy subjects (n = 16). RESULTS: We found that visfatin levels were significantly increased in unstable carotid atherosclerotic plaque secretome than in non-atherosclerotic mammary artery secretome. No differences were found with regard the other adipo/cytokines studied. Regarding visfatin circulating levels, there were no differences between unstable carotid atherosclerotic plaque and non-atherosclerotic mammary artery group. However, these visfatin levels were increased in comparison to serum cohort of healthy subjects. CONCLUSIONS: Of all the adipo/cytokines analysed, only visfatin showed increased levels in secretomes of unstable carotid atherosclerotic plaque. Additional human studies are needed to clarify the possible role of visfatin as prognostic factor of unstable carotid atherosclerotic plaque. PMID- 27391231 TI - A new hydroxynaphthyl benzothiazole derived fluorescent probe for highly selective and sensitive Cu(2+) detection. AB - A new reactive probe, 1-(benzo[d]thiazol-2-yl)naphthalen-2-yl-picolinate (BTNP), was designed and synthesized. BTNP acts as a highly selective probe to Cu(2+) in DMSO/H2O (7/3, v/v, Tris-HCl 10mM, pH=7.4) solution based on Cu(2+) catalyzed hydrolysis of the picolinate ester moiety in BTNP, which leads to the formation of an ESIPT active product with dual wavelength emission enhancement. The probe also possesses the advantages of simple synthesis, rapid response and high sensitivity. The pseudo-first-order reaction rate constant was calculated to be 0.205min(-1). Moreover, application of BTNP to Cu(2+) detection in living cells and real water samples was also explored. PMID- 27391232 TI - Novel Use of Flu Surveillance Data: Evaluating Potential of Sentinel Populations for Early Detection of Influenza Outbreaks. AB - Influenza causes significant morbidity and mortality each year, with 2-8% of weekly outpatient visits around the United States for influenza-like-illness (ILI) during the peak of the season. Effective use of existing flu surveillance data allows officials to understand and predict current flu outbreaks and can contribute to reductions in influenza morbidity and mortality. Previous work used the 2009-2010 influenza season to investigate the possibility of using existing military and civilian surveillance systems to improve early detection of flu outbreaks. Results suggested that civilian surveillance could help predict outbreak trajectory in local military installations. To further test that hypothesis, we compare pairs of civilian and military outbreaks in seven locations between 2000 and 2013. We find no predictive relationship between outbreak peaks or time series of paired outbreaks. This larger study does not find evidence to support the hypothesis that civilian data can be used as sentinel surveillance for military installations. We additionally investigate the effect of modifying the ILI case definition between the standard Department of Defense definition, a more specific definition proposed in literature, and confirmed Influenza A. We find that case definition heavily impacts results. This study thus highlights the importance of careful selection of case definition, and appropriate consideration of case definition in the interpretation of results. PMID- 27391233 TI - Child and adolescent psychiatry patients coming of age: a retrospective longitudinal study of inpatient treatment in Tyrol. AB - BACKGROUND: Mental illness is a common phenomenon at all ages. Various independent studies have shown that psychopathology is often expressed on a continuum from youth to adulthood. The aim of our study was to demonstrate a) the frequency of admission of former child and adolescent psychiatry inpatients (CAP IP) to adult inpatient mental health facilities, and b) a potential longitudinal diagnostic shift. This is the first Austrian study designed to shed light on these issues. METHODS: Nearly 1000 inpatient cases at a specialized child and adolescent care center were analyzed. These cases were then tracked using data matching with registry data from adult psychiatric institutions. Overall, our observational period was 23 years. RESULTS: 26 % of our sample of former CAP-IP used psychiatric inpatient mental health services as adults, thus indicating chronicity or reoccurrence. In line with previous literature, there were patients who stayed in the same diagnostic category as well as patients with a diagnostic shift from childhood to adulthood. CONCLUSIONS: Childhood and adolescence is a very important period for early intervention and prevention of mental illness. Our findings support the notion of the continuity of psychopathology from youth into adulthood. PMID- 27391228 TI - Low protein diets in patients with chronic kidney disease: a bridge between mainstream and complementary-alternative medicines? AB - Dietary therapy represents an important tool in the management of chronic kidney disease (CKD), mainly through a balanced reduction of protein intake aimed at giving the remnant nephrons in damaged kidneys a "functional rest". While dialysis, transplantation, and pharmacological therapies are usually seen as "high tech" medicine, non pharmacological interventions, including diets, are frequently considered lifestyle-complementary treatments. Diet is one of the oldest CKD treatments, and it is usually considered a part of "mainstream" management. In this narrative review we discuss how the lessons of complementary alternative medicines (CAMs) can be useful for the implementation and study of low-protein diets in CKD. While high tech medicine is mainly prescriptive, prescribing a "good" life-style change is usually not enough and comprehensive counselling is required; the empathic educational approach, on which CAMs are mainly, though not exclusively based, may support a successful personalized nutritional intervention.There is no gold-standard, low-protein diet for all CKD patients: from among a relatively vast choice, the best compliance is probably obtained by personalization. This approach interferes with the traditional RCT based analyses which are grounded upon an assumption of equal preference of treatments (ideally blinded). Whole system approaches and narrative medicine, that are widely used in the study of CAMs, may offer ways to integrate EBM and personalised medicine in the search for innovative solutions respecting individualization, but gaining sound data, such as with partially-randomised patient preference trials. PMID- 27391234 TI - Two Multiplex Real-Time PCR Assays to Detect and Differentiate Acinetobacter baumannii and Non- baumannii Acinetobacter spp. Carrying blaNDM, blaOXA-23-Like, blaOXA-40-Like, blaOXA-51-Like, and blaOXA-58-Like Genes. AB - Nosocomial infections caused by Acinetobacter spp. resistant to carbapenems are increasingly reported worldwide. Carbapenem-resistant Acinetobacter (CRA) is becoming a serious concern with increasing patient morbidity, mortality, and lengths of hospital stay. Therefore, the rapid detection of CRA is essential for epidemiological surveillance. Polymerase chain reaction (PCR) has been extensively used for the rapid identification of most pathogens. In this study, we have developed two multiplex real-time PCR assays to detect and differentiate A. baumannii and non-A. baumannii Acinetobacter spp, and common carbapenemase genes, including blaNDM, blaOXA-23-like, blaOXA-40-like, blaOXA-51-like, and blaOXA-58-like. We demonstrate the potential utility of these assays for the direct detection of blaNDM-, blaOXA-23-like-, blaOXA-40-like-, blaOXA-51-like-, and blaOXA-58-like-positive CRA in clinical specimens. Primers were specifically designed, and two multiplex real-time PCR assays were developed: multiplex real time PCR assay1 for the detection of Acinetobacter baumannii 16S-23S rRNA internal transcribed spacer sequence, the Acinetobacter recA gene, and class-B metalloenzyme-encoding gene blaNDM; and multiplex real-time PCR assay2 to detect class-D-oxacillinase-encoding genes (blaOXA-23-like, blaOXA-40-like, blaOXA-51 like,and blaOXA-58-like). The assays were performed on an ABI Prism 7500 FAST Real-Time PCR System. CRA isolates were used to compare the assays with conventional PCR and sequencing. Known amounts of CRA cells were added to sputum and fecal specimens and used to test the multiplex real-time PCR assays. The results for target and nontarget amplification showed that the multiplex real time PCR assays were specific, the limit of detection for each target was 10 copies per 20 MUL reaction volume, the assays were linear over six log dilutions of the target genes (r2 > 0.99), and the Ct values of the coefficients of variation for intra- and interassay reproducibility were less than 5%. The multiplex real-time PCR assays showed 100% concordance with conventional PCR when tested against 400 CRA isolates and their sensitivity for the target DNA in sputum and fecal specimens was 102 CFU/mL. Therefore, these novel multiplex real time PCR assays allow the sensitive and specific characterization and differentiation of blaNDM-, blaOXA-23-like-, blaOXA-40-like-, blaOXA-51-like-, and blaOXA-58-like-positive CRA, making them potential tools for the direct detection of CRA in clinical specimens and the surveillance of nosocomial infections. PMID- 27391235 TI - The Complete Chloroplast Genome of Ye-Xing-Ba (Scrophularia dentata; Scrophulariaceae), an Alpine Tibetan Herb. AB - Scrophularia dentata is an important Tibetan medicinal plant and traditionally used for the treatment of exanthema and fever in Traditional Tibetan Medicine (TTM). However, there is little sequence and genomic information available for S. dentata. In this paper, we report the complete chloroplast genome sequence of S. dentata and it is the first sequenced member of the Sect. Tomiophyllum within Scrophularia (Scrophulariaceae). The gene order and organization of the chloroplast genome of S. dentata are similar to other Lamiales chloroplast genomes. The plastome is 152,553 bp in length and includes a pair of inverted repeats (IRs) of 25,523 bp that separate a large single copy (LSC) region of 84,058 bp and a small single copy (SSC) region of 17,449 bp. It has 38.0% GC content and includes 114 unique genes, of which 80 are protein-coding, 30 are transfer RNA, and 4 are ribosomal RNA. Also, it contains 21 forward repeats, 19 palindrome repeats and 41 simple sequence repeats (SSRs). The repeats and SSRs within S. dentata were compared with those of S. takesimensis and present certain discrepancies. The chloroplast genome of S. dentata was compared with other five publicly available Lamiales genomes from different families. All the coding regions and non-coding regions (introns and intergenic spacers) within the six chloroplast genomes have been extracted and analysed. Furthermore, the genome divergent hotspot regions were identified. Our studies could provide basic data for the alpine medicinal species conservation and molecular phylogenetic researches of Scrophulariaceae and Lamiales. PMID- 27391237 TI - Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self-Efficacy, Problems, And Effects Of Group Therapy. AB - OBJECTIVES: We assessed severely and persistently depressed patients' interpersonal self-efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy. METHOD: Outpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style. RESULTS: Compared to normative samples, patients lacked interpersonal agency, including less self-efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in "agentic and communal" efficacy predicting subsequent decreases in depression. CONCLUSIONS: While severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors. PMID- 27391236 TI - Quantification of Diaphragm Mechanics in Pompe Disease Using Dynamic 3D MRI. AB - BACKGROUND: Diaphragm weakness is the main reason for respiratory dysfunction in patients with Pompe disease, a progressive metabolic myopathy affecting respiratory and limb-girdle muscles. Since respiratory failure is the major cause of death among adult patients, early identification of respiratory muscle involvement is necessary to initiate treatment in time and possibly prevent irreversible damage. In this paper we investigate the suitability of dynamic MR imaging in combination with state-of-the-art image analysis methods to assess respiratory muscle weakness. METHODS: The proposed methodology relies on image registration and lung surface extraction to quantify lung kinematics during breathing. This allows for the extraction of geometry and motion features of the lung that characterize the independent contribution of the diaphragm and the thoracic muscles to the respiratory cycle. RESULTS: Results in 16 3D+t MRI scans (10 Pompe patients and 6 controls) of a slow expiratory maneuver show that kinematic analysis from dynamic 3D images reveals important additional information about diaphragm mechanics and respiratory muscle involvement when compared to conventional pulmonary function tests. Pompe patients with severely reduced pulmonary function showed severe diaphragm weakness presented by minimal motion of the diaphragm. In patients with moderately reduced pulmonary function, cranial displacement of posterior diaphragm parts was reduced and the diaphragm dome was oriented more horizontally at full inspiration compared to healthy controls. CONCLUSION: Dynamic 3D MRI provides data for analyzing the contribution of both diaphragm and thoracic muscles independently. The proposed image analysis method has the potential to detect less severe diaphragm weakness and could thus be used to determine the optimal start of treatment in adult patients with Pompe disease in prospect of increased treatment response. PMID- 27391238 TI - Evidence for Distinguishable Treatment Costs among Paranoid Schizophrenia and Schizoaffective Disorder. AB - BACKGROUND: Schizophrenia spectrum disorders result in enormous individual suffering and financial burden on patients and on society. In Germany, there are about 1,000,000 individuals suffering from schizophrenia (SZ) or schizoaffective disorder (SAD), a combination of psychotic and affective symptoms. Given the heterogeneous nature of these syndromes, one may assume that there is a difference in treatment costs among patients with paranoid SZ and SAD. However, the current the national system of cost accounting in psychiatry and psychosomatics in Germany assesses all schizophrenia spectrum disorders within one category. METHODS: The study comprised a retrospective audit of data from 118 patients diagnosed with paranoid SZ (F20.0) and 71 patients with SAD (F25). We used the mean total costs as well as partial cost, i.e., mean costs for medication products, mean personal costs and mean infrastructure costs from each patient for the statistical analysis. We tested for differences in the four variables between SZ and SAD patients using ANCOVA and confirmed the results with bootstrapping. RESULTS: SAD patients had a longer duration of stay than patients with SZ (p = .02). Mean total costs were significantly higher for SAD patients (p = .023). Further, we found a significant difference in mean personnel costs (p = .02) between patients with SZ and SAD. However, we found no significant differences in mean pharmaceutical costs (p = .12) but a marginal difference of mean infrastructure costs (p = .05) between SZ and SAD. We found neither a common decrease of costs over time nor a differential decrease in SZ and SAD. CONCLUSION: We found evidence for a difference of case related costs of inpatient treatments for paranoid SZ and SAD. The differences in mean total costs seem to be primarily related to the mean personnel costs in patients with paranoid SZ and SAD rather than mean pharmaceutical costs, possibly due to higher personnel effort and infrastructure. PMID- 27391239 TI - Patterns and Environmental Determinants of Medicinal Plant : Vascular Plant Ratios in Xinjiang, Northwest China. AB - With both a full collection of native vascular plant distributions and a full checklist of source plants of the Chinese Materia Medica (CMM), the Uygur Medicine (UM), and the Kazak Medicine (KM) for the Xinjiang region, we defined medicinal plant: vascular plant ratios (simplified as medicinal plant ratios hereafter) as the value of medicinal plant richness divided by vascular plant richness. We aimed to find whether the ratios are constant or change in different environments, which environmental variables determine medicinal plant ratios, and whether the ratios are more influenced by human or by natural environments. Finally, suggestions for medicinal plant conservation were addressed. We found that (1) medicinal plant ratios were not constant, and they were high in the Tarim Basin which was largely covered by desert, while they were relatively low in mountainous areas, especially in the Tianshan Mountains where the general species richness was high; (2) medicinal plant ratios were not significantly influenced by human activities, indicated by human population density distributions, but they were highly correlated with plant species richness and climate, i.e. ratios decreased with plant species richness and MAP, and were related quadratically with MAT; (3) CMM ratio and UM ratio were more influenced by plant richness than by climate, while KM ratio was more influenced by climate. We concluded that the percentages of plants used as medicines were not influenced by distances from human settlements, but were determined by species richness or climate. We suggest that (1), in general, the medicinal plant ratio could be a complementary indicator for medicinal plant conservation planning and (2), for the region of Xinjiang, not only high diversity areas, but also some extreme environments should be considered as compensation for a better protection of medicinal plants. PMID- 27391241 TI - Taking a Step Forward in Laparoscopic Donor Nephrectomy: Transvaginal Retrieval of Donor's Kidney. AB - Laparoscopic donor nephrectomy has been broadly recognized as the gold standard for kidney procurement used in kidney transplantation where it is not uncommon for donors to experience discomfort and aesthetic dissatisfaction over larger incision site. Natural orifice transluminal endoscopic surgery is a surgical approach that allows scarless intraabdominal operations through natural orifices, such as the vagina. In this case report, we describe the first case of transvaginal retrieval of donor's kidney at the National University Hospital, Singapore. A 51-year-old Malay lady with no significant medical history volunteered to a living-related kidney donor. Perioperative antibiotics were administered. A 12 mm Excel port was placed over the left iliac fossa with camera insertion. Two additional ports were inserted over the left rectus sheath edge and left costal margin under direct vision. An additional 5 mm port at the left loin was placed for lateral retraction. A vaginal probe was then inserted to facilitate posterior colpotomy and transection of the left uterosacral ligament. Pneumoperitoneum was subsequently maintained with a LiNA McCartney((r)) Tube. A 15 mm Endocatch((r)) bag was inserted for retrieval of the kidney. The left kidney was placed in the Endocatch bag after transection of the hilar vessels where the kidney was retrieved vaginally with ease. Colpotomy was closed vaginally using Vicryl-0 continuous suture. Total blood loss was noted as 50 mL with warm ischemia time being 7 minutes and the entire retrieval taking totally 20 minutes. Postoperative recovery was uneventful and the donor was discharged stable 3 days postoperation. The transplanted kidney retained normal graft function. Colpotomy retrieval for donor nephrectomy presents an innovative method for specimen retrieval with minimal disruption of donor anatomy. Doing away with laparotomy for kidney retrieval has indeed shown a reduction in recovery time, reduced postoperative pain, and better cosmetic outcome. PMID- 27391240 TI - How Personality Affects Vulnerability among Israelis and Palestinians following the 2009 Gaza Conflict. AB - Can the onset of PTSD symptoms and depression be predicted by personality factors and thought control strategies? A logical explanation for the different mental health outcomes of individuals exposed to trauma would seem to be personality factors and thought control strategies. Trauma exposure is necessary but not sufficient for the development of PTSD. To this end, we assess the role of personality traits and coping styles in PTSD vulnerability among Israeli and Palestinian students amid conflict. We also determine whether gender and exposure level to trauma impact the likelihood of the onset of PTSD symptoms. Five questionnaires assess previous trauma, PTSD symptoms, demographics, personality factors and thought control strategies, which are analyzed using path analysis. Findings show that the importance of personality factors and thought control strategies in predicting vulnerability increases in the face of political violence: the higher stress, the more important the roles of personality and thought control strategies. Thought control strategies associated with introverted and less emotionally stable personality-types correlate positively with higher levels of PTSD symptoms and depression, particularly among Palestinians. By extension, because mental health is key to reducing violence in the region, PTSD reduction in conflict zones warrants rethinking. PMID- 27391242 TI - An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non Alcoholic Steatohepatitis. AB - Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches. PMID- 27391244 TI - Test Anxiety and Salivary Cortisol Levels in Nursing Students. AB - Stress, in the form of test anxiety, inhibits examination performance essential to nursing success. Salivary cortisol, a biomarker of stress, was obtained before 3 examinations and 1 nursing didactic class from a sample of baccalaureate nursing students in a midwestern US university. Significant differences were found between cortisol sampling events and by junior or senior status. These findings suggest that diverse examinations and program level yield differences in stress for students. PMID- 27391245 TI - Student and Faculty Perceptions of iPad Integration in a Prelicensure Program. AB - This article provides an overview of strategies for integration of iPads into a prelicensure nursing program. The study evaluated the actual use of iPads in the classroom, skills and simulation laboratories, and clinical settings and examined the satisfaction of students and faculty with the iPad platform. The study findings provide guidance for a phased-in iPad implementation for prelicensure nursing programs. PMID- 27391243 TI - Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis. AB - BACKGROUND: Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes. METHODS: We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3<120 mg/dL) and the high C3 level group (C3>=120 mg/dL). Patient and renal survivals, association between C3 level and renal pathology were analysed. RESULTS: Serum complement C3 concentration remained in the normal range [78-184 mg/dL]. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P = 0.008) and lower eGFR (P = 0.002) at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P = 0.047 and P = 0.001, respectively). We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P = 0.017, r = -0.407). According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01). Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p = 0.046). No relationship between serum C4 and renal outcome was observed. CONCLUSION: A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival. PMID- 27391246 TI - Teaching Humanity to Nursing Students: Evaluation of an Innovative Teaching Strategy. PMID- 27391247 TI - Application of Fragment Ion Information as Further Evidence in Probabilistic Compound Screening Using Bayesian Statistics and Machine Learning: A Leap Toward Automation. AB - In this work, we introduce an automated, efficient, and elegant model to combine all pieces of evidence (e.g., expected retention times, peak shapes, isotope distributions, fragment-to-parent ratio) obtained from liquid chromatography tandem mass spectrometry (LC-MS/MS/MS) data for screening purposes. Combining all these pieces of evidence requires a careful assessment of the uncertainties in the analytical system as well as all possible outcomes. To-date, the majority of the existing algorithms are highly dependent on user input parameters. Additionally, the screening process is tackled as a deterministic problem. In this work we present a Bayesian framework to deal with the combination of all these pieces of evidence. Contrary to conventional algorithms, the information is treated in a probabilistic way, and a final probability assessment of the presence/absence of a compound feature is computed. Additionally, all the necessary parameters except the chromatographic band broadening for the method are learned from the data in training and learning phase of the algorithm, avoiding the introduction of a large number of user-defined parameters. The proposed method was validated with a large data set and has shown improved sensitivity and specificity in comparison to a threshold-based commercial software package. PMID- 27391249 TI - Tibiofemoral contact forces during walking, running and sidestepping. AB - We explored the tibiofemoral contact forces and the relative contributions of muscles and external loads to those contact forces during various gait tasks. Second, we assessed the relationships between external gait measures and contact forces. A calibrated electromyography-driven neuromusculoskeletal model estimated the tibiofemoral contact forces during walking (1.44+/-0.22ms(-1)), running (4.38+/-0.42ms(-1)) and sidestepping (3.58+/-0.50ms(-1)) in healthy adults (n=60, 27.3+/-5.4years, 1.75+/-0.11m, and 69.8+/-14.0kg). Contact forces increased from walking (~1-2.8 BW) to running (~3-8 BW), sidestepping had largest maximum total (8.47+/-1.57 BW) and lateral contact forces (4.3+/-1.05 BW), while running had largest maximum medial contact forces (5.1+/-0.95 BW). Relative muscle contributions increased across gait tasks (up to 80-90% of medial contact forces), and peaked during running for lateral contact forces (~90%). Knee adduction moment (KAM) had weak relationships with tibiofemoral contact forces (all R(2)<0.36) and the relationships were gait task-specific. Step-wise regression of multiple external gait measures strengthened relationships (0.20 aggression) can be constrained to be equal across the individuals, a model with idiographic measurement of the constructs, but with nomothetic structural relationships can be specified. Three commentaries react to N & M's proposal. Revelle and Wilt challenge the priority given by N & M to unique individual measurement structures, arguing that between subjects differences in structural relationships are empirically important and meaningful. Markus's uses David Hume's framework to raise philosophy of science challenges for N & M's approach. Maydeu-Olivares challenges the incremental validity of N & M's approach, arguing that N & M's approach is unlikely to improve the prediction of between subjects criteria. Finally, N & M present a rejoinder to the three commentaries. PMID- 27391257 TI - Psychological mediators of chronic tinnitus: The critical role of depression. AB - BACKGROUND: Maintenance of chronic tinnitus has been proposed to result from a vicious cycle of hypervigilance occurring when a phantom sound is associated with anxiety and limbic system overactivity. Depression, obsessive-compulsiveness, illness attitudes and coping strategies are known to impact tinnitus, but their relationship with the vicious cycle is unknown. As such, we aimed to identify psychological mediators of the vicious cycle. We also examined the relationship between coping strategies and any identified mediators to facilitate the translation of our research to treatment settings. METHODS: We comprehensively assessed a heterogeneous community sample of 81 people with chronic tinnitus who completed measures assessing their tinnitus and psychological wellbeing. Specifically, we examined the mediating role of depressive symptoms, illness attitudes, and obsessive-compulsiveness in the vicious cycle. RESULTS: While the predicted relationship between tinnitus handicap and anxiety was observed, this was fully mediated by depressive symptoms. In addition, we identified avoidant behaviours and self-blame as maladaptive coping strategies in people with chronic tinnitus and depressive symptoms, identifying potential new treatment targets. LIMITATIONS: This work requires replication in a clinical cohort of people with chronic tinnitus, and further investigations of the role of coping strategies. CONCLUSIONS: These results extend our understanding of the complex role of psychology in the experience of tinnitus, highlighting the importance of depressive symptoms that may be underpinned by functional disruption of specific neurocognitive networks. We have also identified depressive symptoms and maladaptive coping strategies as new treatment targets to improve the health wellbeing of people with chronic tinnitus. PMID- 27391258 TI - Erratum: American Cancer Society Head and Neck Cancer Survivorship Care Guideline. PMID- 27391259 TI - Structural study on the interactions of oxaliplatin and linear DNA. AB - Damage to cellular DNA is believed to determine the cytotoxicity of oxaliplatin. However, high resolution structures formed by oxaliplatin and different linear DNA remain unclear. This study characterized, the key structures of different linear DNA in the platination process by UV absorption spectra and atomic force microscopy (AFM). Bathochromic shift and hyperchromicity in UV spectra after addition of oxaliplatin revealed that it can disrupt base stacking of DNA in the platination process. AFM results of different linear DNA indicated that, the platination process can induce DNA change from an extended conformation to the network structure with many kinks and finally to the compact particles, or toroids with increasing the incubation time. All AFM results confirmed that, platination of different linear DNA by oxaliplatin is a time depended process. The present AFM results provide, structural evidence about the interactions between oxaliplatin and different linear DNA containing multiple targets. SCANNING 38:880-888, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27391260 TI - Adrenomedullin promotes the growth of pancreatic ductal adenocarcinoma through recruitment of myelomonocytic cells. AB - Stromal infiltration of myelomonocytic cells is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and is related to a poor prognosis. However, the detailed mechanism for the recruitment of myelomonocytic cells to pancreatic cancer tissue remains unclear. In the present study, pancreatic cancer cells secreted high levels of adrenomedullin (ADM), and CD11b+ myelomonocytic cells expressed all components of ADM receptors, including GPR182, CRLR, RAMP2 and RAMP3. ADM enhanced the migration and invasion of myelomonocytic cells through activation of the MAPK, PI3K/Akt and eNOS signaling pathways, as well as the expression and activity of MMP-2. ADM also promoted the adhesion and trans-endothelial migration of myelomonocytic cells by increasing expression of VCAM-1 and ICAM-1 in endothelial cells. In addition, ADM induced macrophages and myeloid-derived suppressor cells (MDSCs) to express pro-tumor phenotypes. ADM knockdown in tumor bearing mice or administration of AMA, an ADM antagonist, significantly inhibited the recruitment of myelomonocytic cells and tumor angiogenesis. Moreover, in vivo depletion of myelomonocytic cells using clodronate liposomes suppressed the progression of PDAC. These results reveal a novel function of ADM in PDAC, and suggest ADM is a promising target in the treatment of PDAC. PMID- 27391261 TI - Optogenetic regulation of site-specific subtelomeric DNA methylation. AB - Telomere length homeostasis, critical for chromosomal integrity and genome stability, is controlled by intricate molecular regulatory machinery that includes epigenetic modifications. Here, we examine site-specific and spatiotemporal alteration of the subtelomeric methylation of CpG islands using optogenetic tools to understand the epigenetic regulatory mechanisms of telomere length maintenance. Human DNA methyltransferase3A (DNMT3A) were assembled selectively at chromosome ends by fusion to cryptochrome 2 protein (CRY2) and its interacting complement, the basic helix loop helix protein-1 (CIB1). CIB1 was fused to the telomere-associated protein telomere repeat binding factor-1 (TRF1), which localized the protein complex DNMT3A-CRY2 at telomeric regions upon excitation by blue-light monitored by single-molecule fluorescence analyses. Increased methylation was achieved selectively at subtelomeric CpG sites on the six examined chromosome ends specifically after blue-light activation, which resulted in progressive increase in telomere length over three generations of HeLa cell replications. The modular design of the fusion constructs presented here allows for the selective substitution of other chromatin modifying enzymes and for loci-specific targeting to regulate the epigenetic pathways at telomeres and other selected genomic regions of interest. PMID- 27391262 TI - Microvesicle removal of anticancer drugs contributes to drug resistance in human pancreatic cancer cells. AB - High mortality in pancreatic cancer patients is partly due to resistance to chemotherapy. We describe that human pancreatic cancer cells acquire drug resistance by a novel mechanism in which they expel and remove chemotherapeutic drugs from the microenvironment via microvesicles (MVs). Using human pancreatic cancer cells that exhibit varied sensitivity to gemcitabine (GEM), we show that GEM exposure triggers the cancer cells to release MVs in an amount that correlates with that cell line's sensitivity to GEM. The importance of MV-release in gaining drug resistance in GEM-resistant pancreatic cancer cells was confirmed when the inhibition of MV-release sensitized the cells to GEM treatment, both in vitro and in vivo. Mechanistically, MVs remove drugs that are internalized into the cells and that are in the microenvironment. The differences between the drug resistant and drug-sensitive pancreatic cancer cell lines tested here are explained based on the variable content of influx/efflux proteins present on MVs, which directly dictates the ability of MVs either to trap GEM or to allow GEM to flow back to the microenvironment. PMID- 27391263 TI - Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castration-resistant prostate cancer: A report from the PETRUS prospective study. AB - Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs.Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients. PMID- 27391264 TI - Association of genetic variations in the Wnt signaling pathway genes with myocardial infarction susceptibility in Chinese Han population. AB - : Numerous studies have implicated the Wnt pathway in the development and progression of myocardial infarction (MI); however, there are very few investigations addressing the effects of polymorphisms in the Wnt pathway genes on MI susceptibility. We investigated the possible correlation between genetic variations in Wnt pathway genes and MI risk. Three polymorphisms (rs7832767 C > T in SFRP1 gene, rs2293303 C > T in CTNNB1 gene, rs16893344 C > T in WISP1 gene) were finally selected and genotyped in 465 MI patients and 485 healthy controls, using the PCR-RFLP method. We found that the SFRP1 rs7832767 variant allele (T) was associated with a significantly increased risk of MI [TT vs. CC: adjusted odds ratio (AOR) = 3.13, 95% CI = 1.78-5.51; CT/TT vs. CC: AOR = 1.53, 95% CI = 1.12-2.08; TT vs. CC/CT: AOR = 2.87, 95% CI = 1.66-4.97)]. The significant association with MI risk was also found for the CTNNB1 rs2293303 (CT vs. CC: AOR = 3.48, 95% CI = 2.28-5.33; TT vs. CC: AOR = 7.37, 95% CI = 2.08-26.16; CT/TT vs. CC: AOR = 3.72, 95% CI = 2.46-5.62; TT vs. CC/CT: AOR = 5.52, 95% CI = 1.58 19.28), and WISP1 rs16893344 polymorphisms (CT vs. CC: AOR = 2.43, 95% CI = 1.70 3.47; TT vs. CC: AOR = 5.17, 95% CI = 1.85-14.41; CT/TT vs. CC: AOR = 2.58, 95% CI = 1.83-3.66; TT vs. CC/CT: AOR = 3.88, 95% CI = 1.41-10.64). The associations remain significant in stratified analysis by demographic and clinical characteristics of participants, with few exceptions. Our study provided the first evidence of the association between polymorphisms in the Wnt pathway genes and MI susceptibility in Chinese Han population. Epidemiological studies with larger samples and functional analyses are warranted to further verify our results. PMID- 27391265 TI - Prevalence of Sexually Transmitted Viral and Bacterial Infections in HIV-Positive and HIV-Negative Men Who Have Sex with Men in Toronto. AB - BACKGROUND: Hepatitis B (HBV), hepatitis C (HCV) and other sexually transmitted infections (STIs) have been associated with HIV transmission risk and disease progression among gay men and other men who have sex with men (MSM), but the frequency and distribution of STIs in this community in Canada has not been extensively studied. METHODS: We recruited MSM living with and without HIV from a large primary care clinic in Toronto. Participants completed a detailed socio behavioural questionnaire using ACASI and provided blood for syphilis, HIV, HBV and HCV, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and human cytomegalovirus (CMV) serology, urine for chlamydia and gonorrhea, and a self collected anal swab for human papillomavirus (HPV) molecular diagnostics. Prevalences were expressed as a proportion and compared using chi-square. RESULTS: 442 MSM were recruited, 294 living with HIV and 148 without. Active syphilis (11.0% vs. 3.4%), ever HBV (49.4% vs. 19.1%), HCV (10.4% vs. 3.4%), HSV 2 (55.9% vs. 38.2%), CMV (98.3% vs. 80.3%) and high-risk (HR) anal HPV (67.6% vs. 51.7%) infections were significantly more common in men living with HIV. Chlamydia and gonorrhea were infrequent in both groups. Regardless of HIV infection status, age and number of lifetime male sexual partners were associated with HBV infection and lifetime injection drug use with HCV infection. CONCLUSIONS: Syphilis and viral infections, including HBV, HCV, HSV-2, CMV, and HR-HPV, were common in this clinic-based population of MSM in Toronto and more frequent among MSM living with HIV. This argues for the implementation of routine screening, vaccine-based prevention, and education programs in this high-risk population. PMID- 27391266 TI - Whole Genome Pathway Analysis Identifies an Association of Cadmium Response Gene Loss with Copy Number Variation in Mutant p53 Bearing Uterine Endometrial Carcinomas. AB - BACKGROUND: Massive chromosomal aberrations are a signature of advanced cancer, although the factors promoting the pervasive incidence of these copy number alterations (CNAs) are poorly understood. Gatekeeper mutations, such as p53, contribute to aneuploidy, yet p53 mutant tumors do not always display CNAs. Uterine Corpus Endometrial Carcinoma (UCEC) offers a unique system to begin to evaluate why some cancers acquire high CNAs while others evolve another route to oncogenesis, since about half of p53 mutant UCEC tumors have a relatively flat CNA landscape and half have 20-90% of their genome altered in copy number. METHODS: We extracted copy number information from 68 UCEC genomes mutant in p53 by the GISTIC2 algorithm. GO term pathway analysis, via GOrilla, was used to identify suppressed pathways. Genes within these pathways were mapped for focal or wide distribution. Deletion hotspots were evaluated for temporal incidence. RESULTS: Multiple pathways contributed to the development of pervasive CNAs, including developmental, metabolic, immunological, cell adhesion and cadmium response pathways. Surprisingly, cadmium response pathway genes are predicted as the earliest loss events within these tumors: in particular, the metallothionein genes involved in heavy metal sequestration. Loss of cadmium response genes were associated with copy number changes and poorer prognosis, contrasting with 'copy number flat' tumors which instead exhibited substantive mutation. CONCLUSION: Metallothioneins are lost early in the development of high CNA endometrial cancer, providing a potential mechanism and biological rationale for increased incidence of endometrial cancer with cadmium exposure. Developmental and metabolic pathways are altered later in tumor progression. PMID- 27391268 TI - Anxiety disorders and falls among older adults. AB - BACKGROUND: Falls are common among older adults and can lead to serious injuries, including fractures. We aimed to determine associations between anxiety disorders and falls in older adults. METHODS: Participants were 487 men and 376 women aged >=60 years enrolled in the Geelong Osteoporosis Study, Australia. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition (SCID-I/NP), lifetime history of anxiety disorders was determined. Falls were determined by self-report. In men, a falls-risk score (Elderly Falls Screening Test (EFST)) was also calculated. RESULTS: Among fallers, 24 of 299 (8.0%) had a lifetime history of anxiety disorder compared to 36 of 634 (5.7%) non-fallers (p=0.014). Examination of the association between anxiety and falls suggested differential relationships for men and women. In men, following adjustment for psychotropic medications, mobility and blood pressure, lifetime anxiety disorder was associated with falling (OR 2.96; 95%CI 1.07-8.21) and with EFST score (OR 3.46; 95%CI 1.13 10.6). In women, an association between lifetime anxiety disorder and falls was explained by psychotropic medication use, poor mobility and socioeconomic status. LIMITATIONS: Sub-group analyses involving types of anxiety and anxiety disorders over the past 12-months were not performed due to power limitations. CONCLUSION: Although anxiety disorders were independently associated with a 3-fold increase in likelihood of reported falls and high falls risk among men, an independent association was not detected among women. These results may aid in prevention of falls through specific interventions aimed at reducing anxiety, particularly in men. PMID- 27391267 TI - Testing for clinical inertia in medication treatment of bipolar disorder. AB - BACKGROUND: Clinical inertia has been defined as lack of change in medication treatment at visits where a medication adjustment appears to be indicated. This paper seeks to identify the extent of clinical inertia in medication treatment of bipolar disorder. A second goal is to identify patient characteristics that predict this treatment pattern. METHOD: Data describe 23,406 visits made by 1815 patients treated for bipolar disorder during the STEP-BD practical clinical trial. Visits were classified in terms of whether a medication adjustment appears to be indicated, and also whether or not one occurred. Multivariable regression analyses were conducted to find which patient characteristics were predictive of whether adjustment occurred. RESULTS: 36% of visits showed at least 1 indication for adjustment. The most common indications were non-response to medication, side effects, and start of a new illness episode. Among visits with an indication for adjustment, no adjustment occurred 19% of the time, which may be suggestive of clinical inertia. In multivariable models, presence of any indication for medication adjustment was a predictor of receiving one (OR=1.125, 95% CI =1.015, 1.246), although not as strong as clinical status measures. LIMITATIONS: The associations observed are not necessarily causal, given the study design. The data also lack information about physician-patient communication. CONCLUSIONS: Many patients remained on the same medication regimen despite indications of side effects or non-response to treatment. Although lack of adjustment does not necessarily reflect clinical inertia in all cases, the reasons for this treatment pattern merit further examination. PMID- 27391269 TI - The contemporary face of gender differences and similarities in depression throughout adolescence: Development and chronicity. AB - BACKGROUND: We probe the adolescent gender difference in depression, asking two critical questions. First, most longitudinal studies of gender differences in adolescent depression date from the 1980s and 1990s, raising the need for a body of evidence on whether the developmental pattern is similar or different today. Second, despite the importance of chronicity to depression, we do not know whether there is a gender difference in the chronicity burden of the disorder. METHODS: In a contemporary longitudinal sample of U.S. adolescents, depression symptoms were assessed at ages 11, 13, 15, and 18, and depression diagnoses were assessed at age 20. To capture the chronicity burden of clinical depression, we assessed for every depressive episode in an individual's lifetime and summed the total number of days spent in episode. RESULTS: A gender difference emerged at age 13 for depression symptoms and at ages 13-14 for diagnoses. These findings are similar to those in the 1980s and 1990s despite many social changes that have occurred. However, the magnitude of the gender difference in symptoms at ages 13 and 15 may be larger than those documented previously. Latent growth curve modeling of depression symptoms indicated that girls' symptoms accelerated early in adolescence whereas boys' symptoms accelerated later. Although more girls (24%) than boys (15%) experienced major depression or dysthymia by age 20, the chronicity burden among those with depression showed gender similarities (median=2.6% days depressed for boys and 2.4% for girls). LIMITATIONS: Depression diagnoses were assessed retrospectively; however, symptom data were assessed prospectively, and symptom and diagnostic data converged. The sample was also predominantly White, limiting generalizability. CONCLUSIONS: In a contemporary adolescent sample we observed gender differences in depression symptoms and diagnoses beginning at age 13. We documented distinct developmental trajectories of depression for adolescent girls and boys, suggesting different developmental windows for depression prevention programs. We also discovered a gender similarity in the chronicity burden of clinical depression. PMID- 27391271 TI - Correction: How Reliable Are Current Data for Assessing the Actual Prevalence of Chronic Obstructive Pulmonary Disease? AB - [This corrects the article DOI: 10.1371/journal.pone.0149302.]. PMID- 27391270 TI - Expression and Evaluation of Recombinant Plasmodium knowlesi Merozoite Surface Protein-3 (MSP-3) for Detection of Human Malaria. AB - Malaria remains a major health threat in many parts of the globe and causes high mortality and morbidity with 214 million cases of malaria occurring globally in 2015. Recent studies have outlined potential diagnostic markers and vaccine candidates one of which is the merozoite surface protein (MSP)-3. In this study, novel recombinant Plasmodium knowlesi MSP-3 was cloned, expressed and purified in an Escherichia coli system. Subsequently, the recombinant protein was evaluated for its sensitivity and specificity. The recombinant pkMSP-3 protein reacted with sera from patients with P. knowlesi infection in both Western blot (61%) and ELISA (100%). Specificity-wise, pkMSP-3 did not react with healthy donor sera in either assay and only reacted with a few non-malarial parasitic patient sera in the ELISA assay (3 of 49). In conclusion, sensitivity and specificity of pkMSP-3 was found to be high in the ELISA and Western Blot assay and thus utilising both assays in tandem would provide the best sero-diagnostic result for P. knowlesi infection. PMID- 27391272 TI - Skeletal Muscle Metastases from Squamous Cell Carcinoma of the Cervix: Report of Two Cases With Literature Review. AB - Cervical carcinoma is the second most common female malignancy worldwide. It usually spreads by direct local extension or the lymphatic vessels. Hematogenous dissemination with distant skeletal muscle metastases is a rare phenomenon. We report here 2 patients whose recurrent squamous cell carcinomas of the cervix presented with symptomatic skeletal muscle metastases affecting the muscles of the thoracic wall and forearm, respectively. We also discuss the differential diagnosis and comprehensively review the previously published literature on this rare presentation of cervical carcinoma. PMID- 27391273 TI - Self-Powered Safety Helmet Based on Hybridized Nanogenerator for Emergency. AB - The rapid development of Internet of Things and the related sensor technology requires sustainable power sources for their continuous operation. Scavenging and utilizing the ambient environmental energy could be a superior solution. Here, we report a self-powered helmet for emergency, which was powered by the energy converted from ambient mechanical vibration via a hybridized nanogenerator that consists of a triboelectric nanogenerator (TENG) and an electromagnetic generator (EMG). Integrating with transformers and rectifiers, the hybridized nanogenerator can deliver a power density up to 167.22 W/m(3), which was demonstrated to light up 1000 commercial light-emitting diodes (LEDs) instantaneously. By wearing the developed safety helmet, equipped with rationally designed hybridized nanogenerator, the harvested vibration energy from natural human motion is also capable of powering a wireless pedometer for real-time transmitting data reporting to a personal cell phone. Without adding much extra weight to a commercial one, the developed wearing helmet can be a superior sustainable power source for explorers, engineers, mine-workers under well, as well as and disaster relief workers, especially in remote areas. This work not only presents a significant step toward energy harvesting from human biomechanical movement, but also greatly expands the applicability of TENGs as power sources for self sustained electronics. PMID- 27391275 TI - From the Worm in a Bottle of Mezcal: iDNA Confirmation of a Leech Parasitizing the Antillean Manatee. AB - Invertebrate-derived ingested DNA (iDNA) is quickly proving to be a valuable, non invasive tool for monitoring vertebrate species of conservation concern. Using the DNA barcoding locus, we successfully identified both the blood-feeding leech Haementeria acuecueyetzin and its blood meal-the latter is shown to be derived from the Caribbean manatee, Trichechus manatus . DNA amplification was successful despite the fact that the specimen was fixed in Mezcal (a beverage distilled from agave). We report the first confirmed case of a leech feeding on a manatee, the first record of H. acuecueyetzin for the State of Chiapas and, to our knowledge, the first case of successful DNA amplification of a biological sample fixed in Mezcal other than the caterpillar "worms" more commonly found in that beverage. PMID- 27391276 TI - Single-Step Formation of Pyrimido[4,5-d]pyridazines by a Pyrimidine-Tetrazine Tandem Reaction. AB - A straightforward synthesis of pyrimido[4,5-d]pyridazines from pyrimidines and tetrazines under basic conditions is reported. Deprotonated, substituted 5 halopyrimidines readily react with variously substituted tetrazines in a highly regioselective manner via a complex reaction pathway, which was supported by DFT calculations. This mechanism leads to the empirically observed regioisomers without going through the conceivable hetaryne intermediate. These results on 5 halopyrimidines led to development of the methodology for preparation of opposite regioisomers based on 6-halopyrimidines. PMID- 27391274 TI - Prevalence of Trachoma in Car-Nicobar Island, India after Three Annual Rounds of Mass Drug Administration with Azithromycin. AB - BACKGROUND: A high proportion of active trachoma infection in children of Car Nicobar Island was reported through the Trachoma Rapid Assessment survey conducted in year 2010 by the same researchers. Annual mass drug treatment with azithromycin was administered from years 2010-12 to all individuals residing in this island for reducing the burden of active trachoma infection. A cross sectional prevalence survey was conducted in the year 2013 to assess the post treatment burden of trachoma in this population. METHODS: In the 15 randomly selected compact segments from each village of the island, children aged 1-9 years were examined for evidence of active trachoma infection and participants aged ten years and above were examined for trachomatous trichiasis and corneal opacity. RESULTS: A total of 809 children (1-9 years) and 2735 adults were examined. Coverage with azithromycin for all the three rounds was more than 80%. The prevalence of active trachoma infection in children aged 1-9 years old was 6.8% (95% CI 5.1, 8.5) and Trachomatous Trichiasis (TT) was 3.9% (95% CI 3.2, 4.6). The risk factors associated with active trachoma infection were older age and unclean faces. The risk factors associated with TT were older age and lower literacy level. CONCLUSION: Trachoma has not been eliminated from Car-Nicobar Island in accordance to 'Global Elimination of Trachoma, 2020' guidelines. Sustained efforts and continuous surveillance admixed with adequate programmatic response is imperative for elimination of trachoma in the island. PMID- 27391277 TI - IFAR JULY EDITORIAL. PMID- 27391279 TI - Evidence for Cation-Controlled Excited-State Localization in a Ruthenium Polypyridyl Compound. AB - The visible absorption and photoluminescence (PL) properties of the four neutral ruthenium diimine compounds [Ru(bpy)2(dcb)] (B2B), [Ru(dtb)2(dcb)] (D2B), [Ru(bpy)2(dcbq)] (B2Q), and [Ru(dtb)2(dcbq)] (D2Q), where bpy is 2,2'-bipyridine, dcb is 4,4'-(CO2(-))2-bpy, dtb is 4,4'-(tert-butyl)2-bpy, and dcbq is 4,4'-(CO2( ))2-2,2'-biquinoline, are reported in the presence of Lewis acidic cations present in fluid solutions at room temperature. In methanol solutions, the measured spectra were insensitive to the presence of these cations, while in acetonitrile a significant red shift in the PL spectra (<=1400 cm(-1)) was observed consistent with stabilization of the metal-to-ligand charge transfer (MLCT) excited state through Lewis acid-base adduct formation. No significant spectral changes were observed in control experiments with the tetrabutylammonium cation. Titration data with Li(+), Na(+), Mg(2+), Ca(2+), Zn(2+), Al(3+), Y(3+), and La(3+) showed that the extent of stabilization saturated at high cation concentration with magnitudes that scaled roughly with the cation charge-to-size ratio. The visible absorption spectra of D2Q was particularly informative due to the presence of two well-resolved MLCT absorption bands: (1) Ru -> bpy, lambdamax ~ 450 nm; and (2) Ru -> dcbq, lambdamax ~ 540 nm. The higher-energy band blue shifted and the lower-energy band red-shifted upon cation addition. The PL intensity and lifetime of the excited state of B2B first increased with cation addition without significant shifts in the measured spectra, behavior attributed to a cation-induced change in the localization of the emissive excited state from bpy to dcb. The importance of excited-state localization and stabilization for solar energy conversion is discussed. PMID- 27391278 TI - Crystal structure of zebrafish complement 1qA globular domain. AB - C1q contains three globular domains (C1qgD) that are the key functional component of the classical complement system. C1qgD can interact with important immune molecules, including IgG and C-reactive protein (CRP) to form defense systems to protect animals. Here, the first non-mammalian structure, zebrafish C1qA globular domain (Dare-C1qAgD) was solved. Although the overall architecture of Dare-C1qAgD is similar to human C1qA, residues involved in C1qBgD, C1qCgD, and CRP binding are somewhat different while residues involved in IgG binding are not present in zebrafish. The structure gives insight into how human and fish C1qA evolved from an ancestral protein. PMID- 27391280 TI - Ecosystem nitrogen fixation throughout the snow-free period in subarctic tundra: effects of willow and birch litter addition and warming. AB - Nitrogen (N) fixation in moss-associated cyanobacteria is one of the main sources of available N for N-limited ecosystems such as subarctic tundra. Yet, N2 fixation in mosses is strongly influenced by soil moisture and temperature. Thus, temporal scaling up of low-frequency in situ measurements to several weeks, months or even the entire growing season without taking into account changes in abiotic conditions cannot capture the variation in moss-associated N2 fixation. We therefore aimed to estimate moss-associated N2 fixation throughout the snow free period in subarctic tundra in field experiments simulating climate change: willow (Salix myrsinifolia) and birch (Betula pubescens spp. tortuosa) litter addition, and warming. To achieve this, we established relationships between measured in situ N2 fixation rates and soil moisture and soil temperature and used high-resolution measurements of soil moisture and soil temperature (hourly from May to October) to model N2 fixation. The modelled N2 fixation rates were highest in the warmed (2.8 +/- 0.3 kg N ha-1 ) and birch litter addition plots (2.8 +/- 0.2 kg N ha-1 ), and lowest in the plots receiving willow litter (1.6 +/ 0.2 kg N ha-1 ). The control plots had intermediate rates (2.2 +/- 0.2 kg N ha-1 ). Further, N2 fixation was highest during the summer in the warmed plots, but was lowest in the litter addition plots during the same period. The temperature and moisture dependence of N2 fixation was different between the climate change treatments, indicating a shift in the N2 fixer community. Our findings, using a combined empirical and modelling approach, suggest that a longer snow-free period and increased temperatures in a future climate will likely lead to higher N2 fixation rates in mosses. Yet, the consequences of increased litter fall on moss associated N2 fixation due to shrub expansion in the Arctic will depend on the shrub species' litter traits. PMID- 27391281 TI - Glomerular infiltration by intravascular large B-cell lymphoma. PMID- 27391282 TI - Boyle Studies: Aspects of the Life and Thought of Robert Boyle (1627-91). PMID- 27391283 TI - Structures and Rotational Barriers of a Diiodobinorsnoutane: Energetic Preference for Gauche Conformation. AB - The diiodobinorsnoutane, bi(5-iodopentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-yl) (5), exists in a sterically hindered gauche conformation rather than an anti or an averaged (freely rotating) C2v structure. Density functional theory (DFT) predictions place the gauche conformation 11 kcal/mol more stable than the anti conformation with a barrier of 17 kcal/mol connecting the minima. These are consistent with variable-temperature NMR (17.1 +/- 0.8 kcal/mol) estimates and X ray analysis. Predictions of the torsional profiles of the yet-unsynthesized bromo-, chloro-, and fluoro- analogues show a progressive lowering of the barriers. PMID- 27391284 TI - Changes in division of labour and tasks within public dentistry: relationship to employees work demands, health and work ability. AB - OBJECTIVE: By 2023, fewer dentists are expected in Sweden, at the same time as the demand for dental care is expected to increase. Older people, in particular, are expected to require more dental health than previous generations. To meet this demand, the public sector dentistry in Sweden is moving towards changes in division of labour among dental professionals, including dentists, dental hygienists and dental nurses. However, the impact of this reallocation on the physical and psychosocial wellbeing of employees is unknown. The aim of this study was to compare workplaces with an equal or larger proportion of dental hygienists than dentists (HDH) with workplaces with a larger proportion of dentists than dental hygienists (HD) on the physical and psychosocial work load, musculoskeletal and psychosomatic disorders and sickness presence. MATERIAL: A total of 298 persons employed in the Public Dental Service in a Swedish County Council participated in this study. CONCLUSION: The medium large clinics HDH reported 85% of employee's with considerably more high psychosocial demands compared to employees in medium HD (53%) and large HD (57%). Employees in medium large clinics HDH also reported sleep problems due to work (25%) compared with employees in medium large clinics HD (6%), large clinics HD (11%) and small clinics HDH (3%). Clinic size does not seem to influence the outcome of the HD and HD clinics to any great extent. Of all employees, about 94-100% reported high precision demands and 78-91% poor work postures. PMID- 27391285 TI - Context for Practice: Algorithm for Venous Leg Ulcers, Static Air Support Surface for Prevention of Pressure Injuries, Impact of Ostomy Surgery for Muslim Patients. PMID- 27391286 TI - View From Here: Building and Justifying a Comprehensive WOC Nurse Team. PMID- 27391287 TI - Educational Intervention for Nutrition Education in Patients Attending an Outpatient Wound Care Clinic: A Feasibility Study. AB - PURPOSE: The purpose of this study was to determine whether nurses could use a structured intervention to educate patients with wounds about foods that promote healing and whether this educational intervention could be provided in a cost effective manner. DESIGN: Cross-sectional survey. SUBJECTS AND SETTING: The study was conducted at an outpatient wound care center located on a hospital campus in the Southern United States; 3 full-time nurses and 2 nurses employed on part-time status delivered the intervention. METHODS: A nutrition education intervention was developed through collaborative efforts of a registered dietitian and a nurse. A cross-sectional survey design was used to (1) evaluate nurses' perceptions of the intervention and (2) identify barriers to implementation of the intervention. Direct costs related to materials and nursing time required to deliver the intervention were calculated. RESULTS: Participants indicated they were competent to deliver the structured intervention, and all were willing to continue its use. Survey results indicated that nurses believed the intervention was beneficial to their patients and they indicated that patients were responsive to the intervention. The intervention was found to be low cost ($8.00 per teaching session); no barriers to implementation of the intervention were identified. CONCLUSION: The results of this exploratory study suggest that a structured nutrition education intervention can be provided by nurses in outpatient wound clinics at low cost. Further study is needed to determine the impact of this intervention on nutritional intake and wound healing. PMID- 27391288 TI - Pressure Injury Prevention in a Saudi Arabian Intensive Care Unit: Registered Nurse Attitudes Toward Prevention Strategies and Perceived Facilitators and Barriers to Evidence Implementation. AB - PURPOSE: The purpose of this study was to examine RNs' attitudes toward pressure injury (PI) prevention strategies. Barriers and facilitators perceived by RNs to potentially impact on the adoption and implementation of PI prevention interventions in the intensive care unit (ICU) were examined. DESIGN: Descriptive cross-sectional survey. SUBJECTS AND SETTING: The target population was RNs practicing in an intensive care unit (ICU) of a major tertiary hospital, King Abdul-Aziz, Mecca, in Saudi Arabia. Fifty-six of the available 60 ICU RNs participated in this study. METHODS: Data were collected via survey using the Attitude towards Pressure injury Prevention instrument, which included 13 items rated with 4-point Likert scale, and the modified Barriers and Facilitators tool, which included 27 items. The survey was organized into 3 parts: demographic information, potential barriers to optimal skin care, and potential facilitators to skin care. The survey took 10 to 15 minutes to complete. Data were analyzed with descriptive-correlation statistics and multiple regression analysis. Thematic analysis was undertaken for qualitative data. RESULTS: Participants demonstrated positive attitudes toward PI prevention (MU = 38.19/52; 73.44%). No significant differences were found between demographic characteristics of the participants with the RNs' Attitude subscale and perceived barriers and facilitators associated with implementing PI prevention in the critical care setting. Several barriers influenced the ability of RNs to implement PI prevention strategies including time demands (beta = .388; P = .011), limitation of RNs' knowledge (beta = -.632; P = .022), and current documentation format (beta = .344; P = .046). Statistically significant facilitating factors that increased respondents ability to undertake PI prevention were ease of obtaining pressure-reduction surfaces (beta = -.388; P = .007), collaboration with interdisciplinary teams (beta = .37; P = .02), and availability of appropriate skin care products (beta = .44; P = .015). Thematic analysis of open-ended questions highlighted workload as a barrier that impedes the implementation of care specific to PI prevention. CONCLUSION: Findings from this study highlighted that ICU RNs had a positive attitude toward PI prevention. This study also identified perceived factors influencing PI prevention in the ICU, both facilitators and barriers. Perceived facilitators included availability of pressure-relieving support surfaces and appropriate skin care products and collaboration with the healthcare professional team. However, perceived barriers included limited PI prevention knowledge of the nurse and RN workflow (time demands and documentation format). Findings from this study provide important information identifying context-specific factors that may influence the adoption and implementation of PI prevention interventions in the ICU. PMID- 27391289 TI - Static Air Support Surfaces to Prevent Pressure Injuries: A Multicenter Cohort Study in Belgian Nursing Homes. AB - PURPOSE: The aim of this study was to investigate the incidence and risk factors for developing pressure injuries (PIs) in patients placed on a static air support surfaces: mattress overlay, heel wedge, and seat cushion. DESIGN: Multicenter cohort study. SUBJECTS AND SETTING: The sample comprised 176 residents; their mean age was 87 (SD = 6.76) years; their mean Braden Scale score was 14 (SD = 2.54). The study was performed on a convenience sample of 6 nursing homes in Belgium. METHODS: Data were collected on 23 care units. The primary outcome measure, cumulative PI incidence (category [stage] II-IV) over a 30-day observation period, was calculated. Pressure injury occurrence was defined according to the 2014 European and US National Pressure Injury Advisory panels, Pan Pacific Pressure Injury Alliance classification system. RESULTS: The PI incidence for category (stage) II-IV was 5.1%. Six residents (3.4%) developed a category II PI, and 3 (1.7%) developed a category III PI; no category IV ulcers occurred. No significant risk factors for category II-IV PIs were identified using multivariate logistic regression. Time of sitting in a chair was found to be a risk factor for development of nonblanchable erythema (category I PI) (odds ratio = 21.608; 95% confidence interval [CI], 20.510-22.812; P = .013). The median time to develop a category II-IV PI was 16 days (interquartile range = 2 26). The interrater reliability between the observations of the researcher and nurses on-site was almost perfect (0.86; 95% CI, 0.81-0.91). CONCLUSION: We found a low incidence of PIs when using a static air overlay mattress for patients at risk in a nursing home population. Static air support surfaces, alongside patient tailored patient repositioning protocols, should be considered to prevent PIs in this patient population. PMID- 27391290 TI - View From Here: Caring for Persons With Ostomies in Saudi Arabia. PMID- 27391291 TI - Indwelling Urinary Catheter-Related Problems After Laparoscopic Radical Prostatectomy. AB - PURPOSE: The purpose of this study was to determine occurrence rates of catheter related problems and their association to pertinent clinical characteristics in men with indwelling urinary catheters following laparoscopic radical prostatectomy. STUDY DESIGN: Descriptive, correlational study. SUBJECTS AND SETTING: One hundred twelve men who underwent laparoscopic radical prostatectomy between December 2010 and December 2012 at the Leiden University Medical Centre in the Netherlands were included in this study. After surgery, a Charriere 20 (20F) silicone catheter was left indwelling for 1 week. METHODS: Data were gathered from 2 sources; we reviewed participants' medical records, and participants completed a questionnaire designed for this study. Pearson chi tests were used to analyze associations between dichotomous and ordinal variables and catheter-related problems. Univariate logistic regression analyses were used to analyze the relationships between continuous factors and catheter-related problems. RESULTS: Seventy-five percent of participants reported at least 1 catheter-related problem. Univariate regression analyses revealed correlations between body weight and experiencing catheter-related problems (odds ratio [OR] = 1.050; P = .028) and between body mass index and experiencing catheter-related problems (OR = 1.159; P = .049). CONCLUSION: Indwelling catheter-related problems after laparoscopic radical prostatectomy are prevalent, and they may occur at any time during the entire period of catheter use. High body mass index and high body weight were associated with an increased likelihood of catheter-related problems following radical prostatectomy. PMID- 27391292 TI - Useful Test-Taking Strategies When Preparing for the WOCNCB Continence Examination. PMID- 27391294 TI - WOCN(r)-Accredited Professional Education Programs. PMID- 27391293 TI - Preventing Facial Pressure Ulcers in Acute Respiratory Distress Syndrome (ARDS). AB - BACKGROUND: In patients with acute lung injury and/or severe acute respiratory distress syndrome (ARDS), prone positioning is a therapeutic intervention to improve oxygenation. Positioning a patient in a prone position increases the risk of medical device-related pressure ulcers in the facial area. CASE STUDIES: This article summarizes experience with 4 patients with ARDS. Two did not receive pressure ulcer preventive measures and subsequently developed multiple necrotic facial pressure ulcers related to prone positioning for treatment of ARDS. The other 2 patients were managed on a thin silicone foam dressing; neither of these patients developed facial pressure ulcers during pronation therapy. CONCLUSION: The use of thin soft silicone foam dressings may prevent the development of facial deep tissue injuries in patients receiving prolonged pronation therapy. PMID- 27391295 TI - Static Air Support Surfaces to Prevent Pressure Injuries: A Multicenter Cohort Study in Belgian Nursing Homes. PMID- 27391296 TI - Therapeutic protein-drug interactions: plausible mechanisms and assessment strategies. AB - INTRODUCTION: Over the last three decades, therapeutic proteins have played an increasingly important role in pharmacotherapy. Owing to an expected significant increase in the coadministration of biotherapeutics with established pharmacotherapy regimens or even with other biotherapeutic agents, there is an increasing likelihood for the occurrence of clinically relevant drug interactions, so called therapeutic protein-drug interactions (TP-DIs). AREAS COVERED: Our current understanding of TP-DIs and recent collaborations among industry, academia and regulatory agencies are reviewed in this article. Although most of the observed TP-DIs are mediated by disease states, immune status, and/or target physiology, TP-DI assessments are still done empirically. Plausible mechanisms of major TP-DIs involving therapeutic proteins (primarily monoclonal antibodies), either as victims or as perpetrators, are proposed, with mechanism based strategies and assessment approaches to better evaluate their propensity are recommended. EXPERT OPINION: Our current understanding of the mechanisms of TP-DIs is in its infancy. Much of the basic research needs to be conducted to verify existing TP-DI hypotheses or help predict and manage potential ones, whose efforts are not considered trivial and may be better achieved through close collaborations among scientists from academia, industry, and regulatory agencies. PMID- 27391298 TI - Supercritical Fluid Facilitated Disintegration of Hexagonal Boron Nitride Nanosheets to Quantum Dots and Its Application in Cells Imaging. AB - Preparation of quantum dots (QDs) and exfoliation of two-dimensional layered materials have gathered significant attention in recent days. Though, there are number of attempts have been reported, facile and efficient methodology is yet to be explored. Here, we demonstrate supercritical fluid processing approach for rapid and facile synthesis of blue luminescent BN QDs from layered bulk material via in situ exfoliation followed by disintegration. The microscopic and AFM analysis confirmed the few layer BN QDs formation. The strong luminescent behavior of BN QDs is utilized to stain Gram-negative bacterial cells specifically in the presence of Gram-positive bacterial cells. PMID- 27391297 TI - Pulmonary Function after Treatment for Childhood Cancer. A Report from the St. Jude Lifetime Cohort Study (SJLIFE). AB - RATIONALE: The relationship between treatment-related impairment of pulmonary function in adult survivors of childhood cancer and subsequent physical function has not been studied. OBJECTIVES: In this prospective evaluation of 606 adult survivors of childhood cancer, we sought to determine the risk factors for, as well as the functional impact of, clinically ascertained pulmonary function impairment. METHODS: We measured FEV1, FVC, total lung capacity (TLC), and single breath diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DlCOcorr), expressing the results as percent predicted and lower limit of normal (LLN) values, and we also assessed functional exercise capacity (6-minute-walk distance). Lung radiation exposure was expressed as the estimated percentage of lung tissue that received at least 10 Gy (V10). Associations of clinical and treatment factors with pulmonary function measures were assessed using log-binomial regression to calculate relative risks and 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: The participants' median age at evaluation was 34.2 years, and the median elapsed time from diagnosis was 21.9 years. Among the sample population, 50.7% had an FEV1 percent predicted less than 80%, 47.2% had an FVC percent predicted less than 80%, 31.2% had a TLC percent predicted less than 75%, and 44.6% had DlCOcorr percent predicted less than 75%. Also, 49.0% had FEV1 less than the LLN on the basis of the Global Lung Function Initiative (GLI) criteria, and 45.4% had FVC less than LLN. Obstructive lung defects (FEV1/FVC, <0.7) were found in 0.8%, but none had obstructive lung defects on the basis of the GLI criterion of FEV1/FVC less than the LLN. Restrictive lung defects (TLC, <75%) were found in 31.2% of participants. V10 and elapsed time since diagnosis were associated with abnormal FEV1 and FVC based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 criteria, and with abnormal FEV1 using the GLI criterion. Age at diagnosis was an additional risk factor for abnormal FVC based on the GLI criteria. Age at diagnosis and V10 were associated with abnormal TLC. Increased body mass index, V10, and elapsed time since diagnosis were risk factors for abnormal DlCOcorr. Abnormal pulmonary function tests were associated with decreased 6-minute walk distance. CONCLUSIONS: Impaired pulmonary function in adult survivors of childhood cancer is associated with decreased physical function. These patients may benefit from interventions designed to preserve and/or improve pulmonary function. PMID- 27391299 TI - Effects of imbalanced muscle loading on hip joint development and maturation. AB - The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1128-1136, 2017. PMID- 27391300 TI - Charging single Co atoms on ultrathin NaCl films. AB - Single Co adatoms adsorbed on a double-layer NaCl film supported by Cu(111) were negatively charged after applying a positive voltage pulse to the sample in a scanning tunnelling microscope. Density functional calculations showed that the magnetic moment of Co changed from 3MUB to 2.2MUB after charge state manipulation. PMID- 27391302 TI - Arthur C. Cope Scholar Awards / ACS Inorganic Nanoscience Award: R. E. Schaak / Priestley Medal: T. J. Marks. PMID- 27391303 TI - Effect of prewarming EDTA blood samples to 37 degrees C on platelet count measured by Sysmex XT-2000iV in dogs, cats, and horses. AB - BACKGROUND: Pseudothrombocytopenia secondary to platelet clumping is a common cause of preanalytic error for platelet counts in dogs, cats, and horses. In human beings, it is suggested that prewarming blood samples to 37 degrees C prior to hematology analysis will reduce platelet clumping. OBJECTIVES: The purpose of the study was to evaluate the effect of prewarming EDTA blood samples to 37 degrees C on measured platelet counts and other hematologic variables. METHODS: The EDTA blood samples from dogs, cats and horses submitted to the clinical pathology laboratory at the University of Cambridge were included. Complete blood cell counts performed using a Sysmex XT-2000iV hematology analyzer were done on samples at room temperature (approximately 22 degrees C) and following warming of the samples to 37 degrees C in a water bath. The Wilcoxon signed rank test was used to compare hematologic variables, including platelet count, before and after sample warming to 37 degrees C. Data are presented as median (25(th) , 75(th) percentile) increase. RESULTS: Blood samples from 39 dogs, 19 cats, and 10 horses were included. Sample warming to 37 degrees C resulted in a statistically significant increase in platelet counts in dogs (11 [-2, 30] *10(9) /L), cats (36 [14, 84] *10(9) /L), and horses (42 [31, 79] *10(9) /L). Sample warming did not significantly affect other hematologic variables. CONCLUSIONS: Prewarming EDTA blood samples to 37 degrees C prior to hematologic analysis increased platelet counts overall in canine, feline, and equine blood, but did not abrogate platelet clumping and pseudothrombocytopenia fully in some cases. Furthermore, true pseudothrombocytopenia was not confirmed in these animals. PMID- 27391301 TI - Generating human hematopoietic stem cells in vitro -exploring endothelial to hematopoietic transition as a portal for stemness acquisition. AB - Advances in cellular reprogramming technologies have created alternative platforms for the production of blood cells, either through inducing pluripotency in somatic cells or by way of direct conversion of nonhematopoietic cells into blood cells. However, de novo generation of hematopoietic stem cells (HSCs) with robust and sustained multilineage engraftment potential remains a significant challenge. Hemogenic endothelium (HE) has been recognized as a unique transitional stage of blood development from mesoderm at which HSCs arise in certain embryonic locations. The major aim of this review is to summarize historical perspectives and recent advances in the investigation of endothelial to hematopoietic transition (EHT) and HSC formation in the context of aiding in vitro approaches to instruct HSC fate from human pluripotent stem cells. In addition, direct conversion of somatic cells to blood and HSCs and progression of this conversion through HE stage are discussed. A thorough understanding of the intrinsic and microenvironmental regulators of EHT that lead to the acquisition of self-renewal potential by emerging blood cells is essential to advance the technologies for HSC production and expansion. PMID- 27391304 TI - Membrane Mediated Antimicrobial and Antitumor Activity of Cathelicidin 6: Structural Insights from Molecular Dynamics Simulation on Multi-Microsecond Scale. AB - The cathelicidin derived bovine antimicrobial peptide BMAP27 exhibits an effective microbicidal activity and moderate cytotoxicity towards erythrocytes. Irrespective of its therapeutic and multidimensional potentiality, the structural studies are still elusive. Moreover, the mechanism of BMAP27 mediated pore formation in heterogeneous lipid membrane systems is poorly explored. Here, we studied the effect of BMAP27 in model cell-membrane systems such as zwitterionic, anionic, thymocytes-like (TLM) and leukemia-like membranes (LLM) by performing molecular dynamics (MD) simulation longer than 100 MUs. All-atom MD studies revealed a stable helical conformation in the presence of anionic lipids, however, significant loss of helicity was identified in TLM and zwitterionic systems. A peptide tilt (~45) and central kink (at residue F10) was found in anionic and LLM models, respectively, with an average membrane penetration of < 0.5 nm. Coarse-grained (CG) MD analysis on a multi-MUs scale shed light on the membrane-dependent peptide and lipid organization. Stable micelle and end-to-end like oligomers were formed in zwitterionic and TLM models, respectively. In contrast, unstable oligomer formation and monomeric BMAP27 penetration were observed in anionic and LLM systems with selective anionic lipid aggregation (in LLM). Peptide penetration up to ~1.5 nm was observed in CG-MD systems with the BMAP27 C-terminal oriented towards the bilayer core. Structural inspection suggested membrane penetration by micelle/end-to-end like peptide oligomers (carpet-model like) in the zwitterionic/TLM systems, and transmembrane-mode (toroidal-pore like) in the anionic/LLM systems, respectively. Structural insights and energetic interpretation in BMAP27 mutant highlighted the role of F10 and hydrophobic residues in mediating a membrane-specific peptide interaction. Free energy profiling showed a favorable (-4.58 kcal mol-1 for LLM) and unfavorable (+0.17 kcal mol-1 for TLM) peptide insertion in anionic and neutral systems, respectively. This determination can be exploited to regulate cell-specific BMAP27 cytotoxicity for the development of potential drugs and antibiotics. PMID- 27391305 TI - Genomic Characterizations of a Newcastle Disease Virus Isolated from Ducks in Live Bird Markets in China. AB - One class I Newcastle disease virus (NDV), designated as duck/Guangxi/1261/2015 (GX1261), was isolated from asymptomatic ducks in live bird markets (LBM) from southern China during the national active surveillance for NDVs in 2015. The complete genome length of GX1261 isolate was 15,198 nucleotides with the gene order of 3'-NP-P-M-F-HN-L-5'. The motif at the cleavage site of F protein was 112ERQER/L117, which was typical of low virulence NDV. Several mutations were identified in the functional domains of F and HN proteins, including fusion peptide, heptad repeat region, transmembrane domains and neutralizing epitopes. Phylogenetic analysis based on the complete F gene revealed that the isolate was clustered into sub-genotype 1c in class I, and showed a high level of similarity with the strains isolated from waterfowl in the United States of America. This is the first report of this kind of virus in the mainland of China. These results demonstrated that GX1261-like viruses might exist in asymptomatic waterfowl, and remain undetected or unidentified. Thus, more investigation needs to be done in order to identify the source of the virus. This study revealed the genetic and phylogenetic characteristics of GX1261 isolate and could help us to better understand the epidemiological context of class I NDV in China. PMID- 27391306 TI - New Primers for Discovering Fungal Diversity Using Nuclear Large Ribosomal DNA. AB - Metabarcoding has become an important tool in the discovery of biodiversity, including fungi, which are the second most speciose group of eukaryotes, with diverse and important ecological roles in terrestrial ecosystems. We have designed and tested new PCR primers that target the D1 variable region of nuclear large subunit (LSU) ribosomal DNA; one set that targets the phylum Ascomycota and another that recovers all other fungal phyla. The primers yield amplicons compatible with the Illumina MiSeq platform, which is cost-effective and has a lower error rate than other high throughput sequencing platforms. The new primer set LSU200A-F/LSU476A-R (Ascomycota) yielded 95-98% of reads of target taxa from environmental samples, and primers LSU200-F/LSU481-R (all other fungi) yielded 72 80% of target reads. Both primer sets have fairly low rates of data loss, and together they cover a wide variety of fungal taxa. We compared our results with these primers by amplifying and sequencing a subset of samples using the previously described ITS3_KYO2/ITS4_KYO3 primers, which amplify the internal transcribed spacer 2 (ITS2) of Ascomycota and Basidiomycota. With approximately equivalent read depth, our LSU primers recovered a greater number and phylogenetic diversity of sequences than the ITS2 primers. For instance, ITS3_KYO2/ITS4_KYO3 primers failed to pick up any members of Eurotiales, Mytilinidiales, Pezizales, Saccharomycetales, or Venturiales within Ascomycota, or members of Exobasidiomycetes, Microbotryomycetes, Pucciniomycetes, or Tremellomycetes within Basidiomycota, which were retrieved in good numbers from the same samples by our LSU primers. Among the OTUs recovered using the LSU primers were 127 genera and 28 species that were not obtained using the ITS2 primers, although the ITS2 primers recovered 10 unique genera and 16 species that were not obtained using either of the LSU primers These features identify the new primer sets developed in this study as useful complements to other universal primers for the study of fungal diversity and community composition. PMID- 27391307 TI - Chilades pandava mothers discriminate among Cycas species during oviposition choice tests, but only in an endemic naive population. AB - Host and non-host plant species communicate with insect herbivores to influence oviposition decisions. We studied if Chilades pandava female adults expressed oviposition preferences among host Cycas species in 2 choice tests, counting 39,420 eggs among assays from 4 butterfly populations. A naive butterfly population from Cycas nongnoochiae habitat oviposited 2.2-fold more eggs on leaves of Cycas species that are susceptible to butterfly herbivory than on leaves of its native host Cycas nongnoochiae. In contrast, Chilades pandava populations experienced with novel Cycas species in Thailand, Philippines, and Guam exhibited no preference in choice tests between leaves of susceptible versus leaves of minimally damaged Cycas species. The results indicated that oviposition deterrents and/or stimulants partly mediate the sustainable relationship between an endemic Cycas species and the naive Chilades pandava population from its habitat. Alternatively, differences in infochemicals among Cycas species do not enable discrimination in oviposition choices for Chilades pandava populations that have experienced Cycas species exhibiting no evolutionary history with Chilades pandava. PMID- 27391308 TI - Identification of HcgC as a SAM-Dependent Pyridinol Methyltransferase in [Fe] Hydrogenase Cofactor Biosynthesis. AB - Previous retrosynthetic and isotope-labeling studies have indicated that biosynthesis of the iron guanylylpyridinol (FeGP) cofactor of [Fe]-hydrogenase requires a methyltransferase. This hypothetical enzyme covalently attaches the methyl group at the 3-position of the pyridinol ring. We describe the identification of HcgC, a gene product of the hcgA-G cluster responsible for FeGP cofactor biosynthesis. It acts as an S-adenosylmethionine (SAM)-dependent methyltransferase, based on the crystal structures of HcgC and the HcgC/SAM and HcgC/S-adenosylhomocysteine (SAH) complexes. The pyridinol substrate, 6 carboxymethyl-5-methyl-4-hydroxy-2-pyridinol, was predicted based on properties of the conserved binding pocket and substrate docking simulations. For verification, the assumed substrate was synthesized and used in a kinetic assay. Mass spectrometry and NMR analysis revealed 6-carboxymethyl-3,5-dimethyl-4 hydroxy-2-pyridinol as the reaction product, which confirmed the function of HcgC. PMID- 27391309 TI - Comparison of weekly administration of cisplatin versus three courses of cisplatin 100 mg/m(2) for definitive radiochemotherapy of locally advanced head and-neck cancers. AB - BACKGROUND: To compare definitive radiochemotherapy with weekly administration of 30-40 mg/m(2) of cisplatin to 100 mg/m(2) of cisplatin on days 1, 22 and 43 for outcomes and toxicity in patients with squamous cell carcinoma of the head-and neck. METHODS: Seventy-five patients receiving radiochemotherapy with weekly cisplatin (30-40 mg/m(2)) were compared to 58 patients receiving radiochemotherapy with 100 mg/m(2) cisplatin on days 1, 22 and 43. Radiochemotherapy regimen plus seven characteristics (age, gender, performance score, tumor site, T-/N-category, histologic grading) were evaluated for locoregional control (LRC), metastases-free survival (MFS) and overall survival (OS). Radiochemotherapy groups were compared for toxicity. RESULTS: On multivariate analysis, improved LRC was associated with cisplatin 100 mg/m(2) (hazard ratio [HR] 1.57; p = 0.008) and female gender (HR 4.37; p = 0.003). Radiochemotherapy regimen was not significantly associated with MFS on univariate analysis (p = 0.66). On multivariate analysis, better MFS was associated with ECOG performance score 0-1 (HR 5.63; p < 0.001) and histological grade 1-2 (HR 1.81; p = 0.002). On multivariate analysis, improved OS was associated with cisplatin 100 mg/m(2) (HR 1.33; p = 0.023), ECOG performance score 0-1 (HR 2.15; p = 0.029) and female gender (HR 1.98; p = 0.026). Cisplatin 100 mg/m(2) was associated with higher rates of grade >=3 hematotoxicity (p = 0.004), grade >=2 renal failure (p = 0.004) and pneumonia/sepsis (p = 0.033). CONCLUSIONS: Radiochemotherapy with 100 mg/m(2) of cisplatin every 3 weeks resulted in better LRC and OS than weekly doses of 30-40 mg/m(2). Given the limitations of a retrospective study, 100 mg/m(2) of cisplatin appears preferable. Since this regimen was associated with considerable acute toxicity, patients require close monitoring. PMID- 27391310 TI - Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy. AB - Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence. PMID- 27391311 TI - Kindler syndrome: the case of two Iranian sisters. AB - Kindler syndrome is a rare autosomal recessive condition, characterized by multiple skin and mucosal abnormalities. Among the latter, esophageal involvement is an infrequent manifestation which may be completely asymptomatic or complicated by dysphagia. We report the case of two sisters presenting with cutaneous features and severe dysphagia. Endoscopic examination showed that the patients were affected by a rare condition named "esophageal web". Both patients showed significant improvement after balloon dilation. Clinicians should be aware of the potential complications of this disease, and the approach by balloon dilation should be considered as primary therapy in Kindler syndrome patients with esophageal web. PMID- 27391312 TI - How efficient are referral hospitals in Uganda? A data envelopment analysis and tobit regression approach. AB - BACKGROUND: Hospitals represent a significant proportion of health expenditures in Uganda, accounting for about 26 % of total health expenditure. Improving the technical efficiency of hospitals in Uganda can result in large savings which can be devoted to expand access to services and improve quality of care. This paper explores the technical efficiency of referral hospitals in Uganda during the 2012/2013 financial year. METHODS: This was a cross sectional study using secondary data. Input and output data were obtained from the Uganda Ministry of Health annual health sector performance report for the period July 1, 2012 to June 30, 2013 for the 14 public sector regional referral and 4 large private not for profit hospitals. We assumed an output-oriented model with Variable Returns to Scale to estimate the efficiency score for each hospital using Data Envelopment Analysis (DEA) with STATA13. Using a Tobit model DEA, efficiency scores were regressed against selected institutional and contextual/environmental factors to estimate their impacts on efficiency. RESULTS: The average variable returns to scale (Pure) technical efficiency score was 91.4 % and the average scale efficiency score was 87.1 % while the average constant returns to scale technical efficiency score was 79.4 %. Technically inefficient hospitals could have become more efficient by increasing the outpatient department visits by 45,943; and inpatient days by 31,425 without changing the total number of inputs. Alternatively, they would achieve efficiency by for example transferring the excess 216 medical staff and 454 beds to other levels of the health system without changing the total number of outputs. Tobit regression indicates that significant factors in explaining hospital efficiency are: hospital size (p < 0.01); bed occupancy rate (p < 0.01) and outpatient visits as a proportion of inpatient days (p < 0.05). CONCLUSIONS: Hospitals identified at the high and low extremes of efficiency should be investigated further to determine how and why production processes are operating differently at these hospitals. As policy makers gain insight into mechanisms promoting hospital services utilization in hospitals with high efficiency they can develop context-appropriate strategies for supporting hospitals with low efficiency to improve their service and thereby better address unmet needs for hospital services in Uganda. PMID- 27391313 TI - Infrared and Raman spectroscopic characterizations on new Fe sulphoarsenate hilarionite (Fe2((III))(SO4)(AsO4)(OH).6H2O): Implications for arsenic mineralogy in supergene environment of mine area. AB - Hilarionite (Fe2 (SO4)(AsO4)(OH).6H2O) is a new Fe sulphoarsenates mineral, which recently is found in the famous Lavrion ore district, Atliki Prefecture, Greece. The spectroscopic study of hilarionite enriches the data of arsenic mineralogy in supergene environment of a mine area. The infrared and Raman means are used to characterize the molecular structure of this mineral. The IR bands at 875 and 905cm(-1) are assigned to the antisymmetric stretching vibrations of AsO4(3-). The IR bands at 1021, 1086 and 1136cm(-1) correspond to the possible antisymmetric and symmetric stretching vibrations of SO4(2-). The Raman bands at 807, 843 and 875cm(-1) clearly show that arsenate components in the mineral structure, which are assigned to the symmetric stretching vibrations (nu1) of AsO4(3-) (807 and 843cm(-1)) and the antisymmetric vibration (nu3) (875cm(-1)). IR bands provide more sulfate information than Raman, which can be used as the basis to distinguish hilarionite from kankite. The powder XRD data shows that hilarionite has obvious differences with the mineral structure of kankite. The thermoanalysis and SEM-EDX results show that hilarionite has more sulfate than arsenate. PMID- 27391314 TI - Applying graphene oxide nano-film over a polycarbonate nanoporous membrane to monitor E. coli by infrared spectroscopy. AB - Nano-biosensors are excellent monitoring tools for rapid, specific, sensitive, inexpensive, in-field, on-line, and/or real-time detection of pathogens in foods, soil, air, and water samples. A variety of nano-materials (metallic, polymeric, and/or carbon-based) were employed to enhance the efficacy, efficiency, and sensitivity of these nano-biosensors, including graphene-based materials, especially graphene oxide (GO)-based materials. GO bears many oxygen-bearing groups, enabling ligand conjugation at the high density critical for sensitive detection. We have fabricated GO-modified nano-porous polycarbonate track-etched (PCTE) membranes that were conjugated to an Escherichia coli-specific antibody (Ab) and used to detect E. coli. The random distribution of nanopores on the PCTE membrane surface and the bright coating of the GO onto the membrane were confirmed by scanning electron microscope. Anti-E. coli beta-gal Abs were conjugated to the GO surface via 1-ethyl-3,3-dimethylaminopropyl carbodiimide hydrochloride-N-hydroxysuccinimide chemistry; antibody coating was confirmed by the presence of a characteristic IR peak near 1600cm(-1). A non-corresponding Ab (anti-Pseudomonas) was used as a negative control under identical conditions. When E. coli interacted anti-E.coli beta-gal with Ab-coated GO-nano-biosensor units, we observed a clear shift in the IR peak from 3373.14 to 3315cm(-1); in contrast, we did not observe any shift in IR peaks when the GO unit was coated with the non-corresponding Ab (anti-Pseudomonas). Therefore, the detection of E. coli using the described GO-nano-sensor unit is highly specific, is highly selective and can be applied for real-time monitoring of E. coli with a detection limit between 100MUg/mL and 10MUg/mL, similar to existing detection systems. PMID- 27391315 TI - Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity. AB - BACKGROUND: Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. METHODS: We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate <3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves. RESULTS: PDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was >=1.66 MUg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. CONCLUSIONS: Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity. PMID- 27391316 TI - Comparison of 3 T and 1.5 T for T2* magnetic resonance of tissue iron. AB - BACKGROUND: T2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5 T but scanners operating at 3 T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3 T vs 1.5 T. METHODS: A total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5 T and 3 T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*. RESULTS: Association between heart and liver T2* at 1.5 T and 3 T was non-linear with good fit (R (2) = 0.954, p < 0.001 for heart white blood (WB) imaging; R (2) = 0.931, p < 0.001 for heart black-blood (BB) imaging; R (2) = 0.993, p < 0.001 for liver imaging). R2* approximately doubled between 1.5 T and 3 T with linear fits for both heart and liver (94, 94 and 105 % respectively). Coefficients of variation for intra- and inter-observer reproducibility, as well as inter-study reproducibility trended to be less good at 3 T (3.5 to 6.5 %) than at 1.5 T (1.4 to 5.7 %) for both heart and liver T2*. Artefact scores for the heart were significantly worse with the 3 T BB sequence (median 4, IQR 2-5) compared with the 1.5 T BB sequence (4 [3-5], p = 0.007). CONCLUSION: Heart and liver T2* and R2* at 3 T show close association with 1.5 T values, but there were more artefacts at 3 T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5 T remains the gold standard for clinical practice. However, in centres where only 3 T is available, equivalent values at 1.5 T may be approximated by halving the 3 T tissue R2* with subsequent conversion to T2*. PMID- 27391317 TI - Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell proliferation by epigenetic silencing of KLF2. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death, especially in China. And the mechanism of its progression remains poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in many cancers, including HCC. CDKN2B antisense RNA1 (ANRIL), a lncRNA, coclustered mainly with p14/ARF has been reported to be dysregulated in gastric cancer, esophageal squamous cell carcinoma, and lung cancer. However, its clinical significance and potential role in HCC is still not documented. METHODS AND RESULTS: In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative real-time polymerase chain reaction (qRT-PCR). ANRIL expression was up-regulated in HCC tissues, and the higher expression of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, taking advantage of loss of function experiments in HCC cells, we found that knockdown of ANRIL expression could impair cell proliferation and invasion and induce cell apoptosis both in vitro and in vivo. We also found that ANRIL could epigenetically repress KLF2 transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. We also found that Sp1 could regulate the expression of ANRIL. CONCLUSION: Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC. PMID- 27391318 TI - Prevalence of chronic kidney disease in diabetic adult out-patients in Tanzania. AB - Despite the increasing number of patients with Diabetes Mellitus in sub-Saharan Africa, the magnitude of chronic kidney disease among diabetics has not been well established. A study done by Janmohamed et al. found chronic kidney disease in 83.7 % of diabetics which is relatively higher than the prevalence reported elsewhere. However this study was conducted in schistosoma endemic area along the shores of Lake Victoria. Schistosomiasis has been reported to cause a range of renal diseases. Interpretation of these findings should therefore take into account the possibility of schistosomiasis as a possible confounder. PMID- 27391319 TI - Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trials. AB - BACKGROUND: It is essential to anticipate and limit the social, economic and sanitary cost of type 2 diabetes (T2D), which is in constant progression worldwide. When blood glucose targets are not achieved with diet and lifestyle intervention, insulin is recommended whether or not the patient is already taking hypoglycaemic drugs. However, the benefit/risk balance of insulin remains controversial. Our aim was to determine the efficacy and safety of insulin vs. hypoglycaemic drugs or diet/placebo on clinically relevant endpoints. METHODS: A systematic literature review (Pubmed, Embase, Cochrane Library) including all randomised clinical trials (RCT) analysing insulin vs. hypoglycaemic drugs or diet/placebo, published between 1950 and 2013, was performed. We included all RCTs reporting effects on all-cause mortality, cardiovascular mortality, death by cancer, cardiovascular morbidity, microvascular complications and hypoglycaemia in adults >= 18 years with T2D. Two authors independently assessed trial eligibility and extracted the data. Internal validity of studies was analyzed according to the Cochrane Risk of Bias tool. Risk ratios (RR) with 95 % confidence intervals (95 % CI) were calculated, using the fixed effect model in first approach. The I(2) statistic assessed heterogeneity. In case of statistical heterogeneity, subgroup and sensitivity analyses then a random effect model were performed. The alpha threshold was 0.05. Primary outcomes were all-cause mortality and cardiovascular mortality. Secondary outcomes were non-fatal cardiovascular events, hypoglycaemic events, death from cancer, and macro- or microvascular complications. RESULTS: Twenty RCTs were included out of the 1632 initially identified studies. 18 599 patients were analysed: Insulin had no effect vs. hypoglycaemic drugs on all-cause mortality RR = 0.99 (95 % CI =0.92 1.06) and cardiovascular mortality RR = 0.99 (95 % CI =0.90-1.09), nor vs. diet/placebo RR = 0.92 (95 % CI = 0.80-1.07) and RR = 0.95 (95 % CI 0.77-1.18) respectively. No effect was found on secondary outcomes either. However, severe hypoglycaemia was more frequent with insulin compared to hypoglycaemic drugs RR = 1.70 (95 % CI = 1.51-1.91). CONCLUSIONS: There is no significant evidence of long term efficacy of insulin on any clinical outcome in T2D. However, there is a trend to clinically harmful adverse effects such as hypoglycaemia and weight gain. The only benefit could be limited to reducing short term hyperglycemia. This needs to be confirmed with further studies. PMID- 27391320 TI - Brn3a and Brn3b knockout mice display unvaried retinal fine structure despite major morphological and numerical alterations of ganglion cells. AB - Ganglion cells (GCs), the retinal output neurons, receive synaptic inputs from bipolar and amacrine cells in the inner plexiform layer (IPL) and send information to the brain nuclei via the optic nerve. Although GCs constitute less than 1% of the total retinal cells, they occur in numerous types and are the first neurons formed during retinal development. Using Brn3a and Brn3b mutant mice in which the alkaline phosphatase gene was knocked-in (Badea et al. [Neuron] 2009;61:852-864; Badea and Nathans [Vision Res] 2011;51:269-279), we studied the general effects after gene removal on the retinal neuropil together with the consequences of lack of development of large numbers of GCs onto the remaining retinal neurons of the same class. We analyzed the morphology, number, and general architecture of various neuronal types presynaptic to GCs, searching for changes secondary to the decrement in the number of their postsynaptic partners, as well as the morphology and distribution of retinal astrocytes, for their strong topographical relation to GCs. We found that, despite GC losses, retinal organization in Brn3 null mice is remarkably similar to that of wild-type controls. J. Comp. Neurol., 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27391321 TI - Effects of a nurse-coordinated prevention programme on health-related quality of life and depression in patients with an acute coronary syndrome: results from the RESPONSE randomised controlled trial. AB - BACKGROUND: Improvement of health-related quality of life (HRQOL) is an important goal in preventive cardiology. HRQOL is also related to depressive symptoms, which represent a common co-morbidity and risk factor in patients with an acute coronary syndrome (ACS). Comprehensive nurse-coordinated prevention programmes (NCPP) in secondary care have been shown to reduce cardiovascular risk, however their effects on HRQOL and depressive symptoms have not been evaluated. We therefore investigated HRQOL and depressive symptoms in a secondary analysis in the RESPONSE trial, evaluating the effect of a NCPP on cardiovascular risk. METHODS: RESPONSE was a multicentre (n = 11) randomised controlled trial in ACS patients in secondary and tertiary healthcare settings evaluating a NCPP. The intervention consisted of four outpatient nurse clinic visits in the first 6 months after the index event, focusing on healthy lifestyles, biometric risk factors and medication adherence, in addition to usual care. The control group received usual care only. The outcome was change in HRQOL as measured by the MacNew questionnaire and change in depressive symptoms as measured by Beck's Depression Inventory (BDI) questionnaire at 12-months follow-up relative to baseline. RESULTS: Of 754 patients randomised, 615 were analysed for HRQOL; 120 for depressive symptoms. At baseline, HRQOL was 5.17 (SD 1.09) and 5.20 (SD1.04) (scale range 1.0 to 7.0) in the intervention and control group, respectively. At 12 months follow-up, HRQOL increased by 0.57 (SD 0.89) in the intervention group as compared with 0.42 (SD 0.90) in the control group (p = 0.03). This increase was observed across all relevant subscales. The BDI decreased by 1.9 in the intervention group as compared with 0.03 in the control group (p = 0.03) (scale range 1.0 to 63). CONCLUSION: Participation in a NCPP is associated with a modest but statistically significant increase in HRQOL, and a decrease of depressive symptoms, both of which are highly relevant to patients. A reduction in depressive symptoms may in addition contribute to a reduction in the overall risk of recurrent events. TRIAL REGISTRATION: Dutch trials register: NTR1290 . Registered 24 April 2008. PMID- 27391322 TI - Gender Difference in Health-Care Expenditure: Evidence from India Human Development Survey. AB - BACKGROUND: While the gender disparity in health and mortality in various stages of life in India is well documented, there is limited evidence on female disadvantage in health-care expenditure (HCE). AIMS: Examine the gender difference in HCE in short-term and major morbidity in India, and understand the role of factors underlying the difference. DATA AND METHODS: Using two rounds of nationally representative panel data-the India Human Development Survey (IHDS) 2004-2005 and 2011-2012 (IHDS I & II)-we calculate morbidity prevalence rate and mean HCE by gender, and examine the adjusted effect of gender on major morbidity related HCE by using a two-part regression model. Further, we performed Oaxaca Blinder decomposition of the gender gap in HCE in major morbidity to understand the contribution of demographic and socio-economic factors. RESULTS: Health-care expenditure on females was systematically lower than on males across all demographic and socio-economic groups. Multivariate analysis confirms that female HCE is significantly lower than male HCE even after controlling demographic and socio-economic factors (beta = -0.148, p = 0.000, CI:-0.206-0.091). For both short-term and major morbidity, a female disadvantage on HCE increased from IHDS I to IHDS II. For instance, the male-female gap in major morbidity related expenditure increased from INR 1298 to INR 4172. A decomposition analysis of gender gap in HCE demonstrates that about 48% of the gap is attributable to differences in demographic and socio-economic factors (endowment effect), whereas 50% of the gap is due to the differential effect of the determinants (coefficient effect). INTERPRETATION: Indians spend less on female health care than on male health care. Most of the gender gap in HCE is not due to differential distribution of factors affecting HCE. PMID- 27391323 TI - Co-morbidity of personality disorder in schizophrenia among psychiatric outpatients in China: data from epidemiologic survey in a clinical population. AB - BACKGROUND: The reported rates of personality disorder (PD) in subjects with schizophrenia (SZ) are quite varied across different countries, and less is known about the heterogeneity of PD among subjects with SZ. We examined the co morbidity of PD among patients who are in the stable phase of SZ. METHOD: 850 subjects were randomly sampled from patients diagnosed with SZ in psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. Co-morbidity of PDs was assessed through preliminary screening and patients were administered several modules of the SCID-II. Evidence of heterogeneity was evaluated by comparing patients diagnosed with SZ with those who presented with either affective disorder or neurosis (ADN). RESULTS: 204 outpatients (24.0 %) in the stable phase of SZ met criteria for at least one type of DSM-IV PD. There was a higher prevalence of Cluster-A (odd and eccentric PD) and C (anxious and panic PD) PDs in SZ (around 12.0 %). The most prevalent PD was the paranoid subtype (7.65 %). Subjects with SZ were significantly more likely to have schizotypal PD (4.4 % vs. 2.1 %, p = 0.003) and paranoid PD (7.6 % vs. 5.4 %, p = 0.034), but much less likely to have borderline, obsessive-compulsive, depressive, narcissistic and histrionic PD. CONCLUSIONS: These findings suggest that DSM-IV PD is common in patients with SZ than in the general population. Patterns of co-morbidity with PDs in SZ are different from ADN. PMID- 27391324 TI - Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmo Diet and Cancer Cohort. AB - OBJECTIVE: Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association. METHODS: In the Malmo Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55-73 years at baseline (1991-96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL) 1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression. RESULTS: Inverse associations with breast cancer were seen in fully adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47 0.90), 0.63 (0.45-0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-alpha, 0.65 (0.43-0.99), p-trend = 0.04. In contrast, those in the highest IL 1beta category had higher risk, 1.71 (1.05-2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer. CONCLUSION: Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer. PMID- 27391325 TI - Mitochondrial Genome Variation after Hybridization and Differences in the First and Second Generation Hybrids of Bream Fishes. AB - Hybridization plays an important role in fish breeding. Bream fishes contribute a lot to aquaculture in China due to their economically valuable characteristics and the present study included five bream species, Megalobrama amblycephala, Megalobrama skolkovii, Megalobrama pellegrini, Megalobrama terminalis and Parabramis pekinensis. As maternal inheritance of mitochondrial genome (mitogenome) involves species specific regulation, we aimed to investigate in which way the inheritance of mitogenome is affected by hybridization in these fish species. With complete mitogenomes of 7 hybrid groups of bream species being firstly reported in the present study, a comparative analysis of 17 mitogenomes was conducted, including representatives of these 5 bream species, 6 first generation hybrids and 6 second generation hybrids. The results showed that these 17 mitogenomes shared the same gene arrangement, and had similar gene size and base composition. According to the phylogenetic analyses, all mitogenomes of the hybrids were consistent with a maternal inheritance. However, a certain number of variable sites were detected in all F1 hybrid groups compared to their female parents, especially in the group of M. terminalis (?) * M. amblycephala (?) (MT*MA), with a total of 86 variable sites between MT*MA and its female parent. Among the mitogenomes genes, the protein-coding gene nd5 displayed the highest variability. The number of variation sites was found to be related to phylogenetic relationship of the parents: the closer they are, the lower amount of variation sites their hybrids have. The second generation hybrids showed less mitogenome variation than that of first generation hybrids. The non-synonymous and synonymous substitution rates (dN/dS) were calculated between all the hybrids with their own female parents and the results indicated that most PCGs were under negative selection. PMID- 27391326 TI - Young People with Intellectual Disability Transitioning to Adulthood: Do Behaviour Trajectories Differ in Those with and without Down Syndrome? AB - BACKGROUND: Young people with intellectual disability exhibit substantial and persistent problem behaviours compared with their non-disabled peers. The aim of this study was to compare changes in emotional and behavioural problems for young people with intellectual disability with and without Down syndrome as they transition into adulthood in two different Australian cohorts. METHODS: Emotional and behavioural problems were measured over three time points using the Developmental Behaviour Checklist (DBC) for those with Down syndrome (n = 323 at wave one) and compared to those with intellectual disability of another cause (n = 466 at wave one). Outcome scores were modelled using random effects regression as linear functions of age, Down syndrome status, ability to speak and gender. RESULTS: DBC scores of those with Down syndrome were lower than those of people without Down syndrome indicating fewer behavioural problems on all scales except communication disturbance. For both groups disruptive, communication disturbance, anxiety and self-absorbed DBC subscales all declined on average over time. There were two important differences between changes in behaviours for these two cohorts. Depressive symptoms did not significantly decline for those with Down syndrome compared to those without Down syndrome. The trajectory of the social relating behaviours subscale differed between these two cohorts, where those with Down syndrome remained relatively steady and, for those with intellectual disability from another cause, the behaviours increased over time. CONCLUSIONS: These results have implications for needed supports and opportunities for engagement in society to buffer against these emotional and behavioural challenges. PMID- 27391327 TI - Multiplexed Spectral Imaging of 120 Different Fluorescent Labels. AB - The number of fluorescent labels that can unambiguously be distinguished in a single image when acquired through band pass filters is severely limited by the spectral overlap of available fluorophores. The recent development of spectral microscopy and the application of linear unmixing algorithms to spectrally recorded image data have allowed simultaneous imaging of fluorophores with highly overlapping spectra. However, the number of distinguishable fluorophores is still limited by the unavoidable decrease in signal to noise ratio when fluorescence signals are fractionated over multiple wavelength bins. Here we present a spectral image analysis algorithm to greatly expand the number of distinguishable objects labeled with binary combinations of fluorophores. Our algorithm utilizes a priori knowledge about labeled specimens and imposes a binary label constraint on the unmixing solution. We have applied our labeling and analysis strategy to identify microbes labeled by fluorescence in situ hybridization and here demonstrate the ability to distinguish 120 differently labeled microbes in a single image. PMID- 27391328 TI - Comparative Analysis of the Biomechanical Behaviour of Two Cementless Short Stems for Hip Replacement: Linea Anatomic and Minihip. AB - A comparative study between two stems (Linea Anatomic and Minihip) has been performed in order to analyse the differences in their biomechanical behaviour, concerning stem micromotions and load transmission between stem and bone. From the corresponding finite element models, a parametric study was carried out to quantify ranges of micromotions taking into account: friction coefficient in the stem-bone interface, press-fit and two types of gait cycle. Micromotions were evaluated for each stem at six different levels along repeated gait cycles. An initial and marked stem subsidence at the beginning of the simulation was observed, followed by an asymptotic decrease due to friction forces. Once migration occurs, a repeated reversible cyclic micromotion is developed and stabilized as gait cycle times are simulated. The general motion pattern exhibited higher amplitude of micromotion for Minihip compared to Linea stem. The load transmission mechanism was analyzed, identifying the main internal forces. The results show higher local forces for Minihip stem up to 80% greater than for Linea stem. The differences of design between Minihip and Linea conditioned different distributions of load, influencing the posterior stress-shielding. Consequently, short stems require high bone stock and quality should, being indicated for young patients with high bone quality. PMID- 27391329 TI - Nuclear factor-kappaB is involved in oxyhemoglobin-induced endothelin-1 expression in cerebrovascular muscle cells of the rabbit basilar artery. AB - The present research was designed to investigate whether endothelin-1 (ET-1) secretion can be induced by oxyhemoglobin and whether nuclear factor kappaB (NF kappaB) is involved in the regulation of ET-1 transcription in cerebrovascular muscle cells. Cerebrovascular muscle cells isolated from a rabbit basilar artery were stimulated by oxyhemoglobin (OxyHb) and ET-1 production was increased significantly in the supernatant. Inhibition of NF-kappaB with pyrrolidine dithiocarbamate and small interfering RNA decreased the expression of ET-1. Nuclear translocation of NF-kappaB and the degradation of IkB-alpha was observed with the stimulation of OxyHb. The supernatant obtained from cerebrovascular muscle cells stimulated by OxyHb produced contractions in arterial rings and was blocked by the ET-1 receptor antagonist (BQ-123). The time course of the OxyHb induced contractions of the basilar artery rings correlated with the time course of the OxyHb-induced ET-1 secretion. The contraction of the basilar artery rings induced by OxyHb was attenuated when the artery rings were preincubated with pyrrolidine dithiocarbamate and SN50 (20 and 10 uM, respectively). These results indicate that cerebrovascular muscle cells may be an important source of ET-1 production after subarachnoid hemorrhage. NF-kappaB was involved in the expression of ET-1 and the inhibition of the NF-kappaB pathway may be beneficial for the treatment of cerebral vasospasm. PMID- 27391330 TI - Smoking and Suicide: A Meta-Analysis. AB - BACKGROUND: Many studies have reported a positive association between smoking and suicide, but the results are inconsistent. This meta-analysis was carried out to estimate the association between smoking and suicidal ideation, suicide plan, suicide attempt, and suicide death. METHODS: Major electronic databases including PubMed, Web of Science, Scopus, and ScienceDirect were searched until May 2015. The reference lists of included studies were screened too. Epidemiological studies addressing the association between smoking and suicidal behaviors were enrolled. The heterogeneity across studies was explored by Q-test and I2 statistic. The possibility of publication bias was assessed using Begg's and Egger's tests and Trim & Fill analysis. The results were reported based on risk ratio (RR) and odds ratio (OR) with 95% confidence intervals (CI) using a random effects model. RESULTS: We identified a total of 8062 references and included 63 studies with 8,063,634 participants. Compared to nonsmokers, the current smokers were at higher risk of suicidal ideation (OR = 2.05; 95% CI: 1.53, 2.58; 8 studies; I2 = 80.8%; P<0.001), suicide plan (OR = 2.36; 95% CI: 1.69, 3.02; 6 studies; I2 = 85.2%; P<0.001), suicide attempt (OR = 2.84; 95% CI: 1.49, 4.19; 5 studies; I2 = 89.6%; (P<0.001), and suicide death (RR = 1.83; 95% CI: 1.64, 2.02; 14 studies; I2 = 49.7%; P = 0.018). CONCLUSIONS: There is sufficient evidence that smoking is associated with an increased risk of suicidal behaviors. Therefore, smoking is a contributing factor for suicide. Although this association does not imply causation, however, smoking prevention and cessation should be the target of suicide prevention programs. PMID- 27391331 TI - TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver. AB - BACKGROUND: The development of hepatocellular carcinoma (HCC) is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR) 4. Pre-cancerogenous events can be modelled in mice by the administration of a single dose of diethylnitrosamine (DEN), with HCC formation depending amongst others on interleukin (IL) 6 production. Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the orthologous human gene, and represent a valid model to study tumour formation in pre-injured cholestatic liver. The aim of this study was to investigate DEN-induced liver injury in TLR4-deficient mice with biliary fibrosis. METHODS: ABCB4-deficient mice on the FVB/NJ genetic background were crossed to two distinct genetic backgrounds (TLR4-sufficient C3H/HeN and TLR4-deficient C3H/HeJ) for more than 10 generations. The two congenic knockout and the two corresponding wild-type mouse lines were treated with a single dose of DEN for 48 hours. Phenotypic differences were assessed by measuring hepatic collagen contents, inflammatory markers (ALT, CRP, IL6) as well as hepatic apoptosis (TUNEL) and proliferation (Ki67) rates. RESULTS: Hepatic collagen accumulation is significantly reduced in ABCB4-/-:TLR4-/-double-deficient mice. After DEN challenge, apoptosis, proliferation and inflammatory markers are decreased in TLR4-deficient in comparison to TLR4-sufficient mice. When combining ABCB4 and TLR4 deficiency with DEN treatment, hepatic IL6 expression and proliferation rates are lowest in fibrotic livers from the double-deficient line. Consistent with these effects, selective digestive tract decontamination in ABCB4 /- mice also led to reduced tumor size and number after DEN. CONCLUSION: This study demonstrates that liver injury upon DEN challenge depends on pre-existing fibrosis and genetic background. The generation of ABCB4-/: TLR4-/- double deficient mice illustrates that TLR4-deficiency protects against hepatic injury in a preclinical mouse model of chronic liver disease. PMID- 27391332 TI - Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis. AB - OBJECTIVE: PELD (Progressive Encephalopathy with or without Lipodystrophy or Celia's Encephalopathy) is a fatal and rare neurodegenerative syndrome associated with the BSCL2 mutation c.985C>T, that results in an aberrant transcript without the exon 7 (Celia seipin). The aim of this study was to evaluate both the process of cellular senescence and the effect of unsaturated fatty acids on preadipocytes from a homozygous c.985C>T patient. Also, the role of aberrant seipin isoform on adipogenesis was studied in adipose-derived human mesenchymal stem cells. MATERIAL AND METHODS: Cellular senescence was evaluated using beta-galactosidase staining of preadipocytes obtained from a homozygous c.985C>T patient. Moreover, these cells were cultured during 24 hours with Intralipid, a soybean oil-based commercial lipid emulsion. The expression of the different BSCL2 transcripts was measured by qPCR. Adipose-derived human mesenchymal stem cells were differentiated to a fat lineage using StemPRO adipogenesis kit, and the expression of BSCL2 transcripts and several adipogenesis-related genes was measured by qPCR. RESULTS: the treatment of preadipocytes with unsaturated fatty acids significantly reduced the expression of the BSCL2 transcript without exon 7 by 34 to 63%. On the other hand, at least in preadipocytes, this mutation does not disturb cellular senescence rate. Finally, during adipocyte differentiation of adipose-derived human mesenchymal stem cells, the expression of adipogenic genes (PPARG, LPIN1, and LPL) increased significantly over 14 days, and noteworthy is that the BSCL2 transcript without exon 7 was differentially expressed by 332 to 723% when compared to day 0, suggesting an underlying role in adipogenesis. CONCLUSIONS: our results suggest that Celia seipin is probably playing an underestimated role in adipocyte maturation, but not in senescence, and its expression can be modified by exogenous factors as fatty acids. PMID- 27391333 TI - Low Genetic Diversity and High Invasion Success of Corbicula fluminea (Bivalvia, Corbiculidae) (Muller, 1774) in Portugal. AB - The Asian clam, Corbicula fluminea, is an invasive alien species (IAS) originally from Asia that has spread worldwide causing major ecological and economic impacts in aquatic ecosystems. Here, we evaluated C. fluminea genetic (using COI mtDNA, CYTb mtDNA and 18S rDNA gene markers), morphometric and sperm morphology variation in Portuguese freshwater ecosystems. The COI marker revealed a single haplotype, which belongs to the Asian FW5 invasive lineage, suggesting a common origin for all the 13 Portuguese C. fluminea populations analysed. Morphometric analyses showed differences between the populations colonizing the North (with the exception of the Lima River) and the Centre/South ecosystems. The sperm morphology examination revealed the presence of biflagellate sperm, a distinctive character of the invasive androgenetic lineages. The low genetic variability of the Portuguese C. fluminea populations and the pattern of sperm morphology have been illuminating for understanding the demographic history of this invasive species. We hypothesize that these populations were derived from a unique introductory event of a Corbicula fluminea FW5 invasive androgenic lineage in the Tejo River, which subsequently dispersed to other Portuguese freshwater ecosystems. The C. fluminea asexual reproductive mode may have assisted these populations to become highly invasive despite the low genetic diversity. PMID- 27391334 TI - Smokers with Self-Reported Mental Health Conditions: A Case for Screening in the Context of Tobacco Cessation Services. AB - BACKGROUND: People with mental health conditions (MHC) smoke at high rates and many die prematurely from smoking-related illnesses. Smoking cessation programs, however, generally do not screen for MHC. This study examined the utility of MHC screening in a large tobacco quitline to determine whether self-reported MHC predicts service utilization and quitting behaviors. METHODS & FINDINGS: A brief set of question on MHC was embedded in the routine intake of a state quitline, and 125,261 smokers calling from June 2012 to September 2015 were asked the questions. Quit attempt rate and 6-month success rate were analyzed for a random subset of participants. Overall, 52.2% of smokers reported at least one MHC. Demographic patterns like gender or ethnic difference in self-reported MHC were similar to that in the general population. Depression disorder was reported most often (38.6%), followed by anxiety disorder (33.8%), bipolar disorder (17.0%), drug/alcohol abuse (11.9%), and schizophrenia (7.9%). Among those reporting any MHC, about two-thirds reported more than 1 MHC. Smokers with MHC received more counseling than smokers with no MHC. Quit attempt rates were high for all three groups (>70%). The probability of relapse was greater for those with more than one MHC than for those with one MHC (p<0.005), which in turn was greater than those with no MHC (p < .01). The six-month prolonged abstinence rates for the three conditions were, 21.8%, 28.6%, and 33.7%, respectively. The main limitation of this study is the use of a non-validated self-report question to assess MHC, even though it appears to be useful for predicting quitting behavior. CONCLUSIONS: Smokers with MHC actively seek treatment to quit. Smoking cessation services can use a brief set of questions to screen for MHC to help identify smokers in need of more intensive treatment to quit smoking. PMID- 27391335 TI - Illusory Distance Modulates Perceived Size of Afterimage despite the Disappearance of Depth Cues. AB - It is known that the perceived size of an afterimage is modulated by the perceived distance between the observer and the depth plane on which the afterimage is projected (Emmert's law). Illusions like Ponzo demonstrate that illusory distance induced by depth cues can also affect the perceived size of an object. In this study, we report that the illusory distance not only modulates the perceived size of object's afterimage during the presence of the depth cues, but the modulation persists after the disappearance of the depth cues. We used an adapted version of the classic Ponzo illusion. Illusory depth perception was induced by linear perspective cues with two tilted lines converging at the upper boundary of the display. Two horizontal bars were placed between the two lines, resulting in a percept of the upper bar to be farther away than the lower bar. Observers were instructed to make judgment about the relative size of the afterimage of the lower and the upper bars after adaptation. When the perspective cues and the bars were static, the illusory effect of the Ponzo afterimage is consistent with that of the traditional size-distance illusion. When the perspective cues were flickering and the bars were static, only the afterimage of the latter was perceived, yet still a considerable amount of the illusory effect was perceived. The results could not be explained by memory of a prejudgment of the bar length during the adaptation phase. The findings suggest that cooccurrences of depth cues and object may link a depth marker for the object, so that the perceived size of the object or its afterimage is modulated by feedback of depth information from higher-level visual cortex even when there is no depth cues directly available on the retinal level. PMID- 27391336 TI - Long non-coding RNA SPRY4-IT1 pormotes colorectal cancer metastasis by regulate epithelial-mesenchymal transition. AB - Colorectal cancer (CRC) remains one of the most common cancers worldwide. Increasing evidence indicates that SPRY4 intronic transcript 1 (SPRY4-IT1) regulate cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of CRC remains largely unknown. Here, we reported that SPRY4-IT1 was upregulated in CRC. Increased SPRY4-IT1 expression in CRC was associated with larger tumor size and higher clinical stage. In vitro experiments revealed that SPRY4-IT1 knockdown significantly inhibited CRC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell proliferation. Further functional assays indicated that SPRY4-IT1 overexpression significantly promoted cell migration and invasion by regulate the epithelial-mesenchymal transition (EMT). Taken together, our study demonstrates that SPRY4-IT1 could act as a functional oncogene in CRC, as well as a potential therapeutic target to inhibit CRC metastasis. PMID- 27391337 TI - Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells. AB - Human epidermal growth factor receptor-2 (HER-2)-positive breast cancer tends to be aggressive, highly metastatic, and drug resistant and spreads rapidly. Studies have indicated that emodin inhibits HER-2 expression. This study compared the HER 2-inhibitory effects of two compounds extracted from rhubarb roots: aloe-emodin (AE) and rhein. Our results indicated that AE exerted the most potent inhibitory effect on HER-2 expression. Treatment of HER-2-overexpressing breast cancer cells with AE reduced tumor initiation, cell migration, and cell invasion. AE was able to suppress YB-1 expression, further suppressing downstream HER-2 expression. AE suppressed YB-1 expression through the inhibition of Twist in HER-2 overexpressing breast cancer cells. Our data also found that AE inhibited cancer metastasis and cancer stem cells through the inhibition of EMT. Interestingly, AE suppressed YB-1 expression through the downregulation of the intracellular integrin-linked kinase (ILK)/protein kinase B (Akt)/mTOR signaling pathway in HER 2-overexpressing breast cancer cells. In vivo study showed the positive result of antitumor activity of AE in nude mice injected with human HER-2-overexpressing breast cancer cells. These findings suggest the possible application of AE in the treatment of HER-2-positive breast cancer. PMID- 27391338 TI - Low level phosphorylation of histone H2AX on serine 139 (gammaH2AX) is not associated with DNA double-strand breaks. AB - Phosphorylation of histone H2AX on serine 139 (gammaH2AX) is an early step in cellular response to a DNA double-strand break (DSB). gammaH2AX foci are generally regarded as markers of DSBs. A growing body of evidence demonstrates, however, that while induction of DSBs always brings about phosphorylation of histone H2AX, the reverse is not true - the presence of gammaH2AX foci should not be considered an unequivocal marker of DNA double-strand breaks. We studied DNA damage induced in A549 human lung adenocarcinoma cells by topoisomerase type I and II inhibitors (0.2 MUM camptothecin, 10 MUM etoposide or 0.2 MUM mitoxantrone for 1 h), and using 3D high resolution quantitative confocal microscopy, assessed the number, size and the integrated intensity of immunofluorescence signals of individual gammaH2AX foci induced by these drugs. Also, investigated was spatial association between gammaH2AX foci and foci of 53BP1, the protein involved in DSB repair, both in relation to DNA replication sites (factories) as revealed by labeling nascent DNA with EdU. Extensive 3D and correlation data analysis demonstrated that gammaH2AX foci exhibit a wide range of sizes and levels of H2AX phosphorylation, and correlate differently with 53BP1 and DNA replication. This is the first report showing lack of a link between low level phosphorylation gammaH2AX sites and double-strand DNA breaks in cells exposed to topoisomerase I or II inhibitors. The data are discussed in terms of mechanisms that may be involved in formation of gammaH2AX sites of different sizes and intensities. PMID- 27391339 TI - Downregulating serine hydroxymethyltransferase 2 (SHMT2) suppresses tumorigenesis in human hepatocellular carcinoma. AB - Serine-glycine biosynthetic pathway diverts the glycolytic intermediate 3 phosphoglycerate to synthesize serine and glycine, of which the latter was found to correlate with cancer cell proliferation. Increased de novo biosynthesis of glycine by serine hydroxymethyltransferase 2 (SHMT2) is the central mechanism to fuel one-carbon pools supporting tumorigenesis. However, the therapeutic potential in targeting SHMT2 in hepatocellular carcinoma (HCC) is unknown. In this study we showed that SHMT2 inhibition significantly suppressed liver tumorigenesis. In vitro, SHMT2-knockdown was found to reduce cell growth and tumorigenicity in Huh-7 and HepG2 liver cancer cells. Moreover SHMT2-knockdown Huh-7 cells failed to form tumor xenograft after subcutaneous inoculation into nude mice. Similarly, inducible SHMT2 inhibition, via doxycycline-added drinking water, was found to reduce tumor incidence and tumor growth in a human tumor xenograft mouse model. SHMT2-knockdown increased the susceptibility of Huh-7 cells to doxorubicin suggesting its potential in combination chemotherapy. Through isotopomer tracing of [2-13C] glycine metabolism, we demonstrated that SHMT2 activity is associated with cancer phenotype. However, overexpression of SHMT2 was insufficient to transform immortalized hepatic cells to malignancy, suggesting that SHMT2 is one of the building blocks in liver cancer metabolism but does not initiate malignant transformation. Moreover, our results suggest that glycine, but not 5,10-methylenetetrahydrofolate, from the SHMT2-mediated enzymatic reaction is instrumental in tumorigenesis. Indeed, we found that SHMT2 knockdown cells exhibited increased glycine uptake. Taken together, our data suggest that SHMT2 may be a potential target in the treatment of human HCC. PMID- 27391340 TI - Notch pathway activation is essential for maintenance of stem-like cells in early tongue cancer. AB - BACKGROUND: Notch pathway plays a complex role depending on cellular contexts: promotes stem cell maintenance or induces terminal differentiation in potential cancer-initiating cells; acts as an oncogene in lymphocytes and mammary tissue or plays a growth-suppressive role in leukemia, liver, skin, and head and neck cancer. Here, we present a novel clinical and functional significance of NOTCH1 alterations in early stage tongue squamous cell carcinoma (TSCC). PATIENTS AND METHODS: We analyzed the Notch signaling pathway in 68 early stage TSCC primary tumor samples by whole exome and transcriptome sequencing, real-time PCR based copy number, expression, immuno-histochemical, followed by cell based biochemical and functional assays. RESULTS: We show, unlike TCGA HNSCC data set, NOTCH1 harbors significantly lower frequency of inactivating mutations (4%); is somatically amplified; and, overexpressed in 31% and 37% of early stage TSCC patients, respectively. HNSCC cell lines over expressing NOTCH1, when plated in the absence of attachment, are enriched in stem cell markers and form spheroids. Furthermore, we show that inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 inhibits spheroid forming capacity, transformation, survival and migration of the HNSCC cells suggesting an oncogenic role of NOTCH1 in TSCC. Clinically, Notch pathway activation is higher in tumors of non-smokers compared to smokers (50% Vs 18%, respectively, P=0.026) and is also associated with greater nodal positivity compared to its non activation (93% Vs 64%, respectively, P=0.029). CONCLUSION: We anticipate that these results could form the basis for therapeutic targeting of NOTCH1 in tongue cancer. PMID- 27391343 TI - PATZ1 induces PP4R2 to form a negative feedback loop on IKK/NF-kappaB signaling in lung cancer. AB - Activation of IKK enhances NF-kappaB signaling to facilitate cancer cell migration, invasion and metastasis. Here, we uncover the existence of a negative feedback loop of IKK. The transcription factor PATZ1 induces protein phosphatase 4 (PP4) regulatory subunit 2 (PP4R2) in an IKK-dependent manner. PP4R2 enhances the binding of PP4 to phosphorylated IKK to inactivate IKK/NF-kappaB signaling during sustained stimulation by cellular stimuli such as growth factors and inflammatory mediators. Matched pair studies reveal that primary lung cancers express more PATZ1 and PP4R2 than lymph node metastases in patients. Ectopic PATZ1 decreases invasion/colonization of lung cancers and prolongs the survival of xenograft mice. These effects of PATZ1 are reversed by downregulating PP4R2. Our results suggest that PATZ1 and PP4R2 provide negative feedback on IKK/NF kappaB signaling to prevent cancer cells from over-stimulation from cellular stimuli; a decline in PATZ1 and PP4R2 is functionally associated with cancer migration/invasion and agents enhancing PATZ1 and PP4R2 are worth exploring to prevent invasion/metastasis of lung cancers. PMID- 27391342 TI - Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations. AB - DMD gene mutations have been associated with the development of Dystrophinopathies. Interestingly, it has been recently reported that DMD is involved in the development and progression of myogenic tumors, assigning DMD a tumor suppressor activity in these types of cancer. However, there are only few reports that analyze DMD in non-myogenic tumors. Our study was designed to examine DMD expression and genetic alterations in non-myogenic tumors using public repositories. We also evaluated the overall survival of patients with and without DMD mutations. We studied 59 gene expression microarrays (GEO database) and RNAseq (cBioPortal) datasets that included 9817 human samples. We found reduced DMD expression in 15/27 (56%) pairwise comparisons performed (Fold-Change (FC) <= 0.70; p-value range = 0.04-1.5x10-20). The analysis of RNAseq studies revealed a median frequency of DMD genetic alterations of 3.4%, higher or similar to other well-known tumor suppressor genes. In addition, we observed significant poorer overall survival for patients with DMD mutations. The analyses of paired tumor/normal tissues showed that the majority of tumor specimens had lower DMD expression compared to their normal adjacent counterpart. Interestingly, statistical significant over-expression of DMD was found in 6/27 studies (FC >= 1.4; p-value range = 0.03-3.4x10-15). These results support that DMD expression and genetic alterations are frequent and relevant in non-myogenic tumors. The study and validation of DMD as a new player in tumor development and as a new prognostic factor for tumor progression and survival are warranted. PMID- 27391344 TI - Downregulated long non-coding RNA CLMAT3 promotes the proliferation of colorectal cancer cells by targeting regulators of the cell cycle pathway. AB - Over-expression of long non-coding RNA (lncRNA)-CLMAT3 is significantly associated with colorectal liver metastasis and is an independent predictor of poor survival for colorectal cancer patients. However, as little is known regarding the role of this gene in the proliferation of colorectal cancer in vitro, we investigated the involvement of lncRNA-CLMAT3 in colorectal cancer cell proliferation. In this study, we demonstrate that lncRNA-CLMAT3 expression was significantly increased in colorectal cancer cells compared with a normal intestinal mucous cell line and that inhibition of lncRNA-CLMAT3 suppressed colorectal cancer cell proliferation in vitro. We also found that this reduced colorectal cancer cell proliferation due to lncRNA-CLMAT3 knockdown is associated with G0/G1 cell-cycle arrest induction and apoptosis enhancement. Furthermore, lncRNA-CLMAT3 knockdown enhanced Cdh1 expression and resulted in p27Kip accumulation via increased Skp2 protein ubiquitination. Taken together, our findings suggest that reducing lncRNA-CLMAT3 inhibits colorectal cancer cell proliferation by affecting cell cycle components. PMID- 27391345 TI - Increasing sensitivity to DNA damage is a potential driver for human ovarian cancer. AB - Ovarian cancer is one of the most common cancers among women, accounting for more deaths than any other gynecological diseases. However, the survival rate for ovarian cancer has not essentially improved over the past thirty years. Thus, to understand the molecular mechanism of ovarian tumorigenesis is important for optimizing the early diagnosis and treating this disease. In this study, we observed obvious DNA lesions, especially DNA double strand breaks (DSBs) accompanying cell cycle checkpoint activation, in the human epithelial ovarian cancer samples, which could be due to the impaired DNA response machinery. Following this line, we found that these DNA damage response-deficient primary cancer cells were hypersensitive to DNA damage and lost their ability to repair the DNA breaks, leading to genomic instability. Of note, three key DNA damage response factors, RNF8, Ku70, and FEN1 exhibited dramatically decreased expression level, implying the dysfunctional DNA repair pathways. Re-expression of wild type RNF8, Ku70, or FEN1 in these cells restored the DNA lesions and also partially rescued the cells from death. Our current study therefore proposes that accumulated DNA lesions might be a potential driver of ovarian cancer and the impaired DNA damage responders could be the targets for clinical treatment. PMID- 27391346 TI - High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement. AB - Overexpression of cytokine receptor-like factor 2 (CRLF2) due to chromosomal rearrangement has been observed in acute lymphoblastic leukemia (ALL) and reported to contribute to oncogenesis and unfavorable outcome in ALL. We studied B-ALL and T-ALL patients without CRLF2 rearrangement and observed that CRLF2 is significantly increased in a subset of these patients. Our study shows that high CRLF2expression correlates with high-risk ALL markers, as well as poor survival. We found that the IKZF1-encoded protein, Ikaros, directly binds to the CRLF2 promoter and regulates CRLF2 expression in leukemia cells. CK2 inhibitor, which can increase Ikaros activity, significantly increases Ikaros binding in ALL cells and suppresses CRLF2 expression in an Ikaros-dependent manner. CRLF2 expression is significantly higher in patients with IKZF1 deletion as compared to patients without IKZF1 deletion. Treatment with CK2 inhibitor also results in an increase in IKZF1 binding to the CRLF2 promoter and suppression of CRLF2 expression in primary ALL cells. We further observed that CK2 inhibitor induces increased H3K9me3 histone modifications in the CRLF2 promoter in ALL cell lines and primary cells. Taken together, our results demonstrate that high expression of CRLF2 correlates with high-risk ALL and short survival in patients without CRLF2 rearrangement. Our results are the first to demonstrate that the IKZF1-encoded Ikaros protein directly suppresses CRLF2 expression through enrichment of H3K9me3 in its promoter region. Our data also suggest that high CRLF2 expression works with the IKZF1 deletion to drive oncogenesis of ALL and has significance in an integrated prognostic model for adult high-risk ALL. PMID- 27391347 TI - SCLLTargeting FGFR1 to suppress leukemogenesis in syndromic and de novo AML in murine models. AB - Although over expression of chimeric FGFR1 kinase consistently leads to the development of AML in the rare Stem Cell Leukemia and Lymphoma syndrome, we now show that overexpression of FGFR1 is also seen in up to 20% of non-syndromic, de novo AML. To determine whether targeting FGFR1 in both of these AML subtypes can suppress leukemogenesis, we evaluated the effects of different FGFR1 inhibitors in a side-by-side comparison for their ability to affect in vitro proliferation in FGFR1 overexpressing murine and human cells lines. Three newly developed pan FGFR inhibitors, AZD4547, BGJ398 and JNJ42756493, show a significantly improved efficacy over the more established FGFR inhibitors, PD173074 and TKI258. To examine whether targeting FGFR1 suppresses leukemogenesis in de novo AML in vivo, we created xenografts in immunocompromized mice from primary, de novo AML that showed > 3-fold increased expression of FGFR1. Using BGJ398, the most potent inhibitor identified in the in vitro studies, AML progression in these mice was significantly suppressed compared with vehicle treated animals and overall survival improved. Importantly, no difference in disease course or survival was seen in AML xenografts that did not show overexpression of FGFR1. These observations support the idea that FGFR1 is a driver oncogene in de novo, FGFR1 overexpressing AML and that molecularly targeted therapies using FGFR1 inhibitors may provide a valuable therapeutic regimen for all FGFR1-overexpressing AML. PMID- 27391348 TI - Elevated expression of the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma. AB - Esophageal adenocarcinoma (EAC) represents the sixth leading cause of cancer related deaths and develops in Barret's esophagus affected tissues. The IGF2 mRNA binding protein IMP2/IGF2BP2/p62 was originally identified as an autoantigen in hepatocellular carcinoma. Aim of this study was to investigate the expression and prognostic role of IMP2 in EAC. Human EAC and Barret's esophagus tissue showed overexpression of IMP2, particularly in tumors of increased size and in metastatic tissues. Molecular classification based on published gene signatures of esophageal cancer revealed a specific subtype, in which the expression of IMP2 is high. According to GO and KEGG pathway analyses, genes showing highly correlated expression with IMP2 are associated with growth, proliferation, metabolism, inflammation, and cancerous processes. Clustering of EAC samples according to published survival marker genes strongly suggests that IMP2 overexpressing samples show poor survival. Finally, IMP2 expression correlated with short survival in patients with EAC or esophageal squamous carcinoma. Our data indicate that IMP2 might be a useful prognostic marker for Barret's esophagus and EAC. PMID- 27391349 TI - Long non-coding RNA-H19 antagonism protects against renal fibrosis. AB - Although long non-coding RNAs (lncRNAs) are important players in the initiation and progression of many pathological processes, the role of lncRNAs in renal fibrosis still remains unclear. We showed that lncRNA-H19 expression was significantly up-regulated in TGF-beta2-induced HK-2 cell fibrosis and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo. H19 knockdown significantly attenuated renal fibrosis in vitro and in vivo. LncRNA-H19, miR-17, and fibronectin constituted to a regulatory network involved in renal fibrosis. We also detected up-regulated H19 expression and down-regulated miR-17 expression in the early and advanced animal models of renal fibrosis. This study indicates that H19 up-regulation contributes to renal fibrosis. H19 inhibition might represent a novel anti-fibrotic treatment in renal diseases. PMID- 27391350 TI - A novel isoflavone, ME-344, targets the cytoskeleton in acute myeloid leukemia. AB - The isoflavone ME-344 is a potent anti-cancer agent with preclinical and clinical efficacy in solid tumors. Yet, the mechanism of action of ME-344 has not been fully defined and the preclinical efficacy in leukemia has not been established. Therefore, we investigated the anti-leukemic properties and mechanism of action of ME-344. In a panel of 7 leukemia cell lines, ME-344 was cytotoxic with an IC50 in the range of 70-260 nM. In addition, ME-344 was cytotoxic to primary AML patient samples over normal hematopoietic cells. In an OCI-AML2 xenograft model, ME-344 reduced tumor growth by up to 95% of control without evidence of toxicity. Mechanistically, ME-344 increased mitochondrial ROS generation in leukemic cells. However, antioxidant treatment did not rescue cell death, suggesting that ME-344 had additional targets beyond the mitochondria. We demonstrated that ME-344 inhibited tubulin polymerization by interacting with tubulin near the colchicine binding site. Furthermore, inhibition of tubulin polymerization was functionally important for ME-344 induced death. Finally, we showed that ME-344 synergizes with vinblastine in leukemia cells. Thus, our study demonstrates that ME-344 displays preclinical efficacy in leukemia through a mechanism at least partly related to targeting tubulin polymerization. PMID- 27391352 TI - Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor alpha. AB - The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor alpha (TNFalpha). Akt kinase is implicated in TNFalpha signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects. The specificity of the peptide reporter was evaluated and shown to be a valid measure of Akt activity in single cells. The effect of TNFalpha treatment on Akt activity was highly heterogeneous between normal and RA subjects, which was not observable in bulk analyses. In 2 RA subjects, a bimodal distribution of Akt activity was observed, primarily due to a subpopulation (21.7%: RA Subject 5; 23.8%: RA Subject 6) of cells in which >60% of the reporter was phosphorylated. These subjects also possessed statistically elevated proteolytic cleavage of the reporter relative to normal subjects, suggesting heterogeneity in Akt and protease activity that may play a role in the RA-affected joint. We expect that chemical cytometry studies pairing peptide reporters with capillary electrophoresis will provide valuable data regarding aberrant kinase activity from small samples of clinical interest. PMID- 27391351 TI - FLT3 is implicated in cytarabine transport by human equilibrative nucleoside transporter 1 in pediatric acute leukemia. AB - FLT3 abnormalities are negative prognostic markers in acute leukemia. Infant leukemias are a subgroup with frequent MLL (KMT2A) rearrangements, FLT3 overexpression and high sensitivity to cytarabine, but dismal prognosis. Cytarabine is transported into cells by Human Equilibrative Nucleoside Transporter-1 (hENT1, SLC29A1), but the mechanisms that regulate hENT1 in acute leukemia have been scarcely studied.We explored the expression and functional link between FLT3 and main cytarabine transporters in 50 pediatric patients diagnosed with acute lymphoblastic leukemia and MLL rearrangement (ALL-MLL+) and other subtypes of leukemia, and in leukemia cell lines.A significant positive correlation was found between FLT3 and hENT1 expression in patients. Cytarabine uptake into cells was mediated mainly by hENT1, hENT2 and hCNT1. hENT1-mediated uptake of cytarabine was transiently abolished by the FLT3 inhibitor PKC412, and this effect was associated with decreased hENT1 mRNA and protein levels. Noticeably, the cytotoxicity of cytarabine was lower when cells were first exposed to FLT3 inhibitors (PKC412 or AC220), probably due to decreased hENT1 activity, but we observed a higher cytotoxic effect if FLT3 inhibitors were administered after cytarabine.FLT3 regulates hENT1 activity and thereby affects cytarabine cytotoxicity. The sequence of administration of cytarabine and FLT3 inhibitors is important to maintain their efficacy. PMID- 27391354 TI - New High-Performance Liquid Chromatography Coupled Mass Spectrometry Method for the Detection of Lobster and Shrimp Allergens in Food Samples via Multiple Reaction Monitoring and Multiple Reaction Monitoring Cubed. AB - Crustacean shellfish allergy ranks among the most frequent and severe food allergies for adults, demanding rugged and sensitive analytical routine methods. The objective of this study was therefore to develop a mass spectrometric approach for the detection of contamination with shrimp and lobster, two economically important types of crustaceans, in complex food matrices. Following a biomarker approach, we identified proteotypic peptides and developed a multiple reaction monitoring (MRM) method allowing for the identification and differentiation of shrimp and lobster in the food matrix at concentrations down to 0.1%. To further enhance sensitivity, we employed the MRM-cubed (MRM(3)) mode, which allowed us to detect crustaceans down to concentrations of 25 MUg/g (crustacean/food, 0.0025%). We hereby present the first mass spectrometric method for the detection of shrimp and lobster in food matrices. PMID- 27391353 TI - Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction. AB - Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs) immortalized by the human telomerase reverse transcriptase (hTERT) gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM) cells were injected into adult (4-6-week-old) Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week old) NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL) were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT 779TL), they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases. PMID- 27391356 TI - Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer. AB - OBJECTIVES: Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. METHODS: Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. RESULTS: Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. CONCLUSIONS: Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II. PMID- 27391355 TI - HIV Infection Is Not Associated with Carotid Intima-Media Thickness in Brazil: A Cross-Sectional Analysis from the INI/ELSA-Brasil Study. AB - BACKGROUND: Carotid intima-media thickness (cIMT) has been used as an early marker of atherosclerotic disease in the general population. Recently its role among HIV-infected patients has been questioned. To date, no Brazilian study has compared cIMT in respect to HIV status. METHODS: We compared data from 535 patients actively followed in a prospective cohort in Rio de Janeiro (HIV group); 88 HIV-negative individuals who were nominated by patients (friend controls-FCs); and 10,943 participants of the ELSA-Brasil study. Linear regression models were used to study associations of the 3 groups and several covariables with cIMT. Propensity scores weighting (PSW) were also employed to balance data. RESULTS: Median thickness in mm (IQR) were 0.54 (0.49,0.62); 0.58 (0.52,0.68); and 0.57 (0.49,0.70), HIV, FCs and ELSA-Brasil groups, respectively (p-value<0.001). The best linear model chosen did not include the group variables, after adjusting for all the variables chosen, showing no difference of cIMT across groups. Similar results were obtained with PSW. Several traditional CVD risk factors were also significantly associated with cIMT: female gender, higher education and higher HDL were negatively associated while risk factors were older age, current/former smoker, AMI/stroke family history, CVD history, hypertension, DM, higher BMI and total cholesterol. CONCLUSIONS: We show for the first time in a middle-income setting that cIMT, is not different in HIV-infected patients in Rio de Janeiro compared with 2 different groups of non-HIV-infected individuals. Traditional CVD risk factors are associated with this outcome. Our results point out that high standards of care and prevention for CVD risk factors should always be sought both in the HIV-infected and non-infected populations to prevent CVD-related events. PMID- 27391357 TI - Secondary Surgery Versus Chemotherapy for Recurrent Ovarian Cancer. AB - OBJECTIVE: The best course of treatment for recurrent ovarian cancer is uncertain. We sought to determine whether secondary cytoreductive surgery for first recurrence of ovarian cancer improves overall survival compared with other treatments. MATERIALS AND METHODS: We assessed survival using Surveillance, Epidemiology and End Results-Medicare data for advanced stage ovarian cancer cases diagnosed from January 1, 1997 to December 31, 2007 with survival data through 2010 using multinomial propensity weighted finite mixture survival regression models to distinguish true from misclassified recurrences. Of 35,995 women ages 66 years and older with ovarian cancer, 3439 underwent optimal primary debulking surgery with 6 cycles of chemotherapy; 2038 experienced a remission. RESULTS: One thousand six hundred thirty-five of 2038 (80%) women received treatment for recurrence of whom 72% were treated with chemotherapy only, 16% with surgery and chemotherapy and 12% received hospice care. Median survival of women treated with chemotherapy alone, surgery and chemotherapy, or hospice care was 4.1, 5.4, and 2.2 years, respectively (P<0.001). Of those receiving no secondary treatments, 75% were likely true nonrecurrences with median survival of 15.9 years and 25% misclassified with 2.4 years survival. Survival among women with recurrence was greater for those treated with surgery and chemotherapy compared with chemotherapy alone (hazard ratio=1.67; 95% confidence interval, 1.13-2.47). Women who were older with more comorbidities and high-grade cancer had worse survival. CONCLUSIONS: Secondary surgery with chemotherapy to treat recurrent ovarian cancer increases survival by 1.3 years compared with chemotherapy alone and pending ongoing randomized trial results, may be considered a standard of care. PMID- 27391358 TI - Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. AB - BACKGROUND: This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. METHODS: To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed. RESULTS: Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex. CONCLUSIONS: Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico-striato-thalamo cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances. PMID- 27391359 TI - Transcriptional networks associated with the immune system are disrupted by organochlorine pesticides in largemouth bass (Micropterus salmoides) ovary. AB - Largemouth bass (Micropterus salmoides) inhabiting Lake Apopka, Florida are exposed to high levels of persistent organochlorine pesticides (OCPs) and dietary uptake is a significant route of exposure for these apex predators. The objectives of this study were to determine the dietary effects of two organochlorine pesticides (p, p'-dichlorodiphenyldichloroethylene; p, p' DDE and methoxychlor; MXC) on the reproductive axis of largemouth bass. Reproductive bass (late vitellogenesis) were fed one of the following diets: control pellets, 125ppm p, p'-DDE, or 10ppm MXC (mg/kg) for 84days. Due to the fact that both p,p' DDE and MXC have anti-androgenic properties, the anti-androgenic pharmaceutical flutamide was fed to a fourth group of largemouth bass (750ppm). Following a 3 month exposure, fish incorporated p,p' DDE and MXC into both muscle and ovary tissue, with the ovary incorporating 3 times more organochlorine pesticides compared to muscle. Endpoints assessed were those related to reproduction due to previous studies demonstrating that these pesticides impact the reproductive axis and we hypothesized that a dietary exposure would result in impaired reproduction. However, oocyte distribution, gonadosomatic index, plasma vitellogenin, and plasma sex steroids (17beta-estradiol, E2 and testosterone, T) were not different between control animals and contaminant-fed largemouth bass. Moreover, neither p, p' DDE nor MXC affected E2 or T production in ex vivo oocyte cultures from chemical-fed largemouth bass. However, both pesticides did interfere with the normal upregulation of androgen receptor that is observed in response to human chorionic gonadotropin in ex vivo cultures, an observation that may be related to their anti-androgenic properties. Transcriptomics profiling in the ovary revealed that gene networks related to cell processes such as leukocyte cell adhesion, ossification, platelet function and inhibition, xenobiotic metabolism, fibrinolysis, and thermoregulation were altered by p, p' DDE, MXC, and flutamide. Interestingly, immune-related gene networks were suppressed by all three chemicals. The data suggest that p, p' DDE and flutamide affected more genes in common with each other than either chemical with MXC, consistent with studies suggesting that p, p' DDE is a more potent anti-androgen than MXC. These data demonstrate that reproductive health was not affected by these specific dietary treatments, but rather the immune system, which may be a significant target of organochlorine pesticides. The interaction between the reproductive and immune systems should be considered in future studies on these legacy and persistent pesticides. PMID- 27391360 TI - Reproductive toxicity of inorganic mercury exposure in adult zebrafish: Histological damage, oxidative stress, and alterations of sex hormone and gene expression in the hypothalamic-pituitary-gonadal axis. AB - Mercury (Hg) is a prominent environmental contaminant that causes a variety of adverse effects on aquatic organisms. However, the mechanisms underlying inorganic Hg-induced reproductive impairment in fish remains largely unknown. In this study, adult zebrafish were exposed to 0 (control), 15 and 30MUg Hg/l (added as mercuric chloride, HgCl2) for 30days, and the effects on histological structure, antioxidant status and sex hormone levels in the ovary and testis, as well as the mRNA expression of genes involved in the hypothalamic-pituitary gonadal (HPG) axis were analyzed. Exposure to Hg caused pathological lesions in zebrafish gonads, and changed the activities and mRNA levels of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)) as well as the content of glutathione (GSH) and malondialdehyde (MDA). In females, although ovarian 17beta-estradiol (E2) content remained relatively stable, significant down-regulation of lhbeta, gnrh2, gnrh3, lhr and eralpha were observed. In males, testosterone (T) levels in the testis significantly decreased after Hg exposure, accompanied by down-regulated expression of gnrh2, gnrh3, fshbeta and lhbeta in the brain as well as fshr, lhr, ar, cyp17 and cyp11b in the testis. Thus, our study indicated that waterborne inorganic Hg exposure caused histological damage and oxidative stress in the gonads of zebrafish, and altered sex hormone levels by disrupting the transcription of related HPG-axis genes, which could subsequently impair the reproduction of fish. Different response of the antioxidant defense system, sex hormone and HPG-axis genes between females and males exposed to inorganic Hg indicated the gender-specific regulatory effect by Hg. To our knowledge, this is the first time to explore the effects and mechanisms of inorganic Hg exposure on reproduction at the histological, enzymatic and molecular levels, which will greatly extend our understanding on the mechanisms underlying of reproductive toxicity of inorganic Hg in fish. PMID- 27391362 TI - Relative Effects of Temperature, Light, and Humidity on Clinging Behavior of Metacercariae-Infected Ants. AB - The lancet fluke, Dicrocoelium dendriticum, is perhaps the best-known example of parasite manipulation of host behavior, which is manifested by a radically changed behavior that leaves infected ants attached to vegetation at times when transmission to an herbivore host is optimal. Despite the publicity surrounding this parasite, curiously little is known about factors inducing and maintaining behavioral changes in its ant intermediate host. This study examined the importance of 3 environmental factors on the clinging behavior of red wood ants, Formica polyctena , infected with D. dendriticum . This behavior, hypothesized to involve cramping of the mandibular muscles in a state of tetany, was observed in naturally infected F. polyctena under controlled temperature, light, and humidity conditions. We found that low temperature significantly stimulated and maintained tetany in infected ants while light, humidity, ant size, and infection intensity had no influence on this behavior. Under none of the experimental conditions did uninfected ants attach to vegetation, demonstrating that tetany was induced by D. dendriticum . Temperature likely has a direct impact on the initiation of clinging behavior, but it may also serve as a simple but reliable indicator of the encounter rate between infected ants and ruminant definitive hosts. In addition, temperature-sensitive behavior manipulation may protect infected ants from exposure to temperatures in the upper thermal range of the host. PMID- 27391361 TI - Relationship between LAPTM4B Gene Polymorphism and Prognosis of Patients following Tumor Resection for Colorectal and Esophageal Cancers. AB - BACKGROUND: Lysosome-associated transmembrane-4 beta (LAPTM4B) is an oncogene that participates tumorgenesis in a variety of human solid tumors, and it has two alleles named as LAPTM4B*1 and *2. The present study aimed to identify the association of LAPTM4B genotype with clinicopathological features and prognosis in colorectal and esophageal cancer patients. METHOD: Genotypes of LAPTM4B were determined by PCR in 167 colon cancer cases (72 patients in a discovery cohort and 95 patients in a testing cohort), 160 rectal cancer cases and 164 esophageal cancer cases. Association between the LAPTM4B gene polymorphism and clinicopathological variables was calculated by Chi-square test or Fisher's exact test. Patient survival differences were calculated by the Kaplan-Meier method. Prognostic factors were determined with Log-rank test and Cox regression model. RESULTS: LAPTM4B *1/1 was more frequently detected in colon cancer patients with lymph node metastasis and TNM III+IV stages in total colon cancer (discovery + testing cohorts). LAPTM4B *2/2 decreased in recurrent patients in total colon cancer patients (P = 0.045). Kaplan-Meier survival curves and Log-rank test showed that LAPTM4B*1 was correlated with shorter overall survival (OS) in discovery and testing cohorts of colon cancer (P = 0.0254 and 0.0292, respectively), but not in rectal and esophageal cancer cases (P = 0.7669 and 0.9356, respectively). Multivariate analysis showed that LAPTM4B genotype was an independent prognostic factor for OS in total colon cancer [P = 0.004, hazard ratio (HR) = 0.432; 95% confidence interval (CI) = 0.243-0.768], but not in rectal and esophageal cancers (P = 0.791, HR = 1.073, 95% CI = 0.638-1.804 and 0.998, HR = 1.000, 95% CI = 0.663-1.530, respectively). CONCLUSION: These findings suggested that LAPTM4B allele *1 was a risk factor associated with poor prognosis in patients with colon cancer, but not in patients with rectal or esophageal cancers. LAPTM4B genotype status might be a useful prognostic indicator for patients that need surgical operation in colon cancer. PMID- 27391363 TI - RIPK3 Is Largely Dispensable for RIG-I-Like Receptor- and Type I Interferon Driven Transcriptional Responses to Influenza A Virus in Murine Fibroblasts. AB - The kinase RIPK3 is a key regulator of cell death responses to a growing number of viral and microbial agents. We have found that influenza A virus (IAV) mediated cell death is largely reliant on RIPK3 and that RIPK3-deficient mice are notably more susceptible to lethal infection by IAV than their wild-type counterparts. Recent studies demonstrate that RIPK3 also participates in regulating gene transcription programs during host pro-inflammatory and innate immune responses, indicating that this kinase is not solely an inducer of cell death and that RIPK3-driven transcriptional responses may collaborate with cell death in promoting clearance of IAV. Here, we carried out DNA microarray analyses to determine the contribution of RIPK3 to the IAV-elicited host transcriptional response. We report that RIPK3 does not contribute significantly to the RLR activated transcriptome or to the induction of type I IFN genes, although, interestingly, IFN-beta production at a post-transcriptional step was modestly attenuated in IAV-infected ripk3-/- fibroblasts. Overall, RIPK3 regulated the expression of <5% of the IAV-induced transcriptome, and no genes were found to be obligate RIPK3 targets. IFN-beta signaling was also found to be largely normal in the absence of RIPK3. Together, these results indicate that RIPK3 is not essential for the host antiviral transcriptional response to IAV in murine fibroblasts. PMID- 27391364 TI - Neural Correlates of Prosocial Behavior: Compensating Social Exclusion in a Four Player Cyberball Game. AB - Prior studies demonstrated contributions of the insula and dorsal anterior cingulate cortex (dACC) for both experiencing and observing social exclusion, but it is not yet well understood how the brain processes the compensation of exclusion, as is observed in prosocial helping. Here, we tested if social brain regions, specifically the medial prefrontal cortex (mPFC) and temporal parietal junction (TPJ) are involved when individuals show prosocial behavior towards excluded others. For this purpose, 23 female participants played a four-player Cyberball Game in which participants could toss balls to each other. During the exclusion game, two players excluded one of the other players. When participants observed exclusion by others, they showed elevated activity in the insula, consistent with prior studies. However, when they tossed the ball to the excluded player, they showed increased activation in the TPJ, consistent with the hypothesis that prosocial behavior is associated with social reasoning. In addition, tossing to the excluded player was associated with increased activity in the nucleus accumbens (NAcc). Given that prior studies reported that the NAcc is involved in experiencing rewards, this may suggest a warm glow for showing prosocial compensation behavior when helping excluded others. PMID- 27391365 TI - Type of the recurrent exotropia after bilateral rectus recession for intermittent exotropia. AB - BACKGROUND: The aim of this study was to investigate the type of exotropia (XT) based on the distance-near (D/N) difference in recurrent XT after bilateral lateral rectus (BLR) recession to treat intermittent XT (IXT) to look into the possibility of secondary convergence insufficiency (CI)-type strabismus. METHODS: A total of 121 patients with recurrent XT after BLR recession for basic-type and divergence excess (DE)-type IXT were retrospectively enrolled at a single institution. The distributions in the XT types were compared according to the D/N difference between primary and recurrent XT. RESULTS: Preoperatively, the population comprised 14 divergence excess (DE) types and 107 basic types. After the BLR recession, the XT-type composition changed to 59 basic types, 33 CI types, and 29 DE types. In one of the 14 preoperatively identified DE-type XT cases, the XT type changed to CI type, it changed to basic type in four cases, and the remaining nine cases showed no change in the DE type. The 107 preoperatively identified basic-type XT cases postoperatively became 55 basic type, 32 CI-type, and 20 DE-type recurrent XT cases, and their postoperative distance XT control grades and near stereoacuity values did not significantly differ. CONCLUSION: The XT type composition changed after the BLR recession. The XT types in recurrent XT after BLR recession showed an increasing proportion of CI-type. We suspect that an individual fusion mechanism might also influence the XT-type in recurrent XT in view of the somewhat increased DE-type in recurrent XT. PMID- 27391366 TI - Codelivery of salinomycin and chloroquine by liposomes enables synergistic antitumor activity in vitro. AB - AIM: To improve the suboptimal therapeutic efficacy of salinomycin (SAL) toward liver cancer cells using chloroquine (CQ) combination by the liposomes co delivering SAL and CQ (SCNL). MATERIALS & METHODS: The synergy of these two drugs was evaluated in liver cancer cells (HepG2) and liver cancer stem cells (LCSCs) by median-effect analysis. SCNL with optimized ratio were developed. The cytotoxic effect and basal autophagy flux (measure of autophagic degradation activity) of various formulations were evaluated. RESULTS & CONCLUSION: CQ could significantly increase the cytotoxic effect of SAL in HepG2 cells, but not in HepG2-LCSCs, due to the greater basal autophagy flux in HepG2 cells. This combination therapy is promising for liver cancer treatment by eradicating liver cancer cells and LCSCs. PMID- 27391367 TI - What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. AB - Cancer-related cognitive impairment (CRCI) is an important clinical problem for cancer patients and survivors. In this review, we summarize studies investigating the occurrence of impaired cognition in patients with haematological malignancies. Most published studies focus on survivors of childhood acute lymphoblastic leukaemia and primary central nervous system lymphoma. We also discuss studies conducted in acute myeloid leukaemia, myelodysplastic syndromes, chronic myeloid leukaemia, Hodgkin lymphoma (HL), non-HL and chronic lymphocytic leukaemia. Although research in this area is still emerging, it appears that a subset of chemotherapy-treated haematological malignancy survivors experience CRCI. Future research should focus on expanding the literature reviewed here with larger studies appropriately powered to assess cognition via objective and subjective measures in a longitudinal fashion to tease apart the impact of disease and the various forms of cancer treatment. PMID- 27391368 TI - Unit cost analysis of training and deploying paid community health workers in three rural districts of Tanzania. AB - BACKGROUND: Tanzania, like other African countries, faces significant health workforce shortages. With advisory and partnership from Columbia University, the Ifakara Health Institute and the Tanzanian Training Centre for International Health (TTCIH) developed and implemented the Connect Project as a randomized cluster experimental trial of the childhood survival impact of recruiting, training, and deploying of a new cadre of paid community health workers (CHW), named "Wawazesha wa afya ya Jamii" (WAJA). This paper presents an estimation of the cost of training and deploying WAJA in three rural districts of Tanzania. METHODS: Costing data were collected by tracking project activity expenditure records and conducting in-depth interviews of TTCIH staff who have led the training and deployment of WAJA, as well as their counterparts at Public Clinical Training Centres who have responsibility for scaling up the WAJA training program. The trial is registered with the International Standard Randomized Controlled Trial Register number ( ISRCTN96819844 ). RESULTS: The Connect training cost was US$ 2,489.3 per WAJA, of which 40.1 % was for meals, 20.2 % for accommodation 10.2 % for tuition fees and the remaining 29.5 % for other costs including instruction and training facilities and field allowance. A comparable training program estimated unit cost for scaling-up this training via regional/district clinical training centres would be US$ 833.5 per WAJA. Of this unit cost, 50.3 % would involve the cost of meals, 27.4 % training fees, 13.7 % for field allowances, 9 % for accommodation and medical insurance. The annual running cost of WAJA in a village will cost US$ 1.16 per capita. CONCLUSION: Costs estimated by this study are likely to be sustainable on a large scale, particularly if existing regional/district institutions are utilized for this program. PMID- 27391369 TI - Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models. AB - BACKGROUND: Reactive astrogliosis is a remarkable pathogenetic hallmark of the brains of Parkinson's disease (PD) patients, but its progressive fate and regulation mechanisms are poorly understood. In this study, growth arrest specific 1 (Gas1), a tumor growth suppressor oncogene, was identified as a novel modulator of the cell apoptosis of reactive astrocytes in primary culture and the injured substantia nigra. METHODS: Animal models and cell cultures were utilized in the present study. Lipopolysaccharide (LPS)- and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated animal models were used to detect Gas1 expression in the brain via immunohistochemistry and western blot. Cell cultures were performed to analyze Gas1 functions in the viability and apoptosis of reactive astrocytes and SH-SY5Y cells by double labeling, CCK-8, LDH, TUNEL, flow cytometry, and siRNA knockdown methods. RESULTS: Gas1 expressions were significantly elevated in the majority of the reactive astrocytes of the brains with LPS or MPTP insults. In the injured substantia nigras, GFAP-positive astrocytes exhibited higher levels of cleaved caspase-3. In cell culture, the up regulated Gas1 expression induced apoptosis of reactive astrocytes that were insulted by LPS in combination with interferon-gamma and tumor necrosis factor-a. This effect was confirmed through siRNA knockdown of Gas1 gene expression. Finally and interestingly, the potential underlying signaling pathways were evidently related to an increase in the Bax/Bcl-2 ratio, the abundant generation of reactive oxygen species and the activation of cleaved caspase-3. CONCLUSIONS: This study demonstrated that the up-regulation of inducible Gas1 contributed to the apoptosis of reactive astrocytes in the injured nigra. Gas1 signaling may function as a novel regulator of astrogliosis and is thus a potential intervention target for inflammatory events in PD conditions. PMID- 27391370 TI - Cardiopulmonary responses during the cooling and the extracorporeal life support rewarming phases in a porcine model of accidental deep hypothermic cardiac arrest. AB - BACKGROUND: This study aimed to assess cardiac and pulmonary pathophysiological responses during cooling and extracorporeal life support (ECLS) rewarming in a porcine model of deep hypothermic cardiac arrest (DHCA). In addition, we evaluated whether providing a lower flow rate of ECLS during the rewarming phase might attenuate cardiopulmonary injuries. METHODS: Twenty pigs were cannulated for ECLS, cooled until DHCA occurred and subjected to 30 min of cardiac arrest. In order to assess the physiological impact of ECLS on cardiac output we measured flow in the pulmonary artery using Doppler echocardiography as well as a modified thermodilution technique using the Swan-Ganz catheter (injection site in the right ventricle). The animals were randomized into two groups during rewarming: a group with a low blood flow rate of 1.5 L/min (LF group) and a group with a normal flow rate of 3.0 L/min (NF group). The ECLS temperature was adjusted to 5 degrees C above the central core. Cardiac output, hemodynamics and pulmonary function parameters were evaluated. RESULTS: During the cooling phase, cardiac output, heart rhythm and blood pressure decreased continuously. Pulmonary artery pressure tended to increase at 32 degrees C compared to the initial value (20.2 +/- 1.7 mmHg vs. 29.1 +/- 5.6 mmHg, p = 0.09). During rewarming, arterial blood pressure was higher in the NF than in the LF group at 20 degrees and 25 degrees C (p = 0.003 and 0.05, respectively). After rewarming to 35 degrees C, cardiac output was 3.9 +/- 0.5 L/min in the NF group vs. 2.7 +/- 0.5 L/min in LF group (p = 0.06). At the end of rewarming under ECLS cardiac output was inversely proportional to the ECLS flow rate. Moreover, the ECLS flow rate did not significantly change pulmonary vascular resistance. DISCUSSION: Using a newly developed experimental model of DHCA treated by ECLS, we assessed the cardiac and pulmonary pathophysiological response during the cooling phase and the ECLS rewarming phase. Despite lower metabolic need during hypothermia, a low ECLS blood flow rate during rewarming did not improved cardiopulmonary injuries after rewarming. CONCLUSION: A low ECLS flow rate during the rewarming phase did not attenuate pulmonary lesions, increased blood lactate level and tended to decrease cardiac output after rewarming. A normal ECLS flow rate did not increase pulmonary vascular resistance compared to a low flow rate. This experimental model on pigs contributes a number of pathophysiological findings relevant to the rewarming strategy for patients who have undergone accidental DHCA. PMID- 27391372 TI - Directed Self-Assembly of Block Copolymer Thin Films Using Minimal Topographic Patterns. AB - We demonstrate that a minimal topographic pattern with a confinement depth (D) much less than the domain spacing of block copolymers (L0) can be used to achieve highly ordered hexagonal arrays or unidirectionally aligned line patterns over large areas. Cylinder-forming poly(styrene-b-ethylene oxide) (PS-b-PEO) thin films were prepared on a series of minimal single trench patterns with different widths (W) and D. Upon thermal annealing, hexagonal arrays of cylindrical microdomains propagated away from the edges of a single trench, providing insight into the minimum pitch (P) of the trench necessary to fully order hexagonal arrays. The confinement trench D of 0.30L0, the W in the range of 1.26L0 to 2.16L0, and the P as long as 18.84L0 were found to be effective for the generation of laterally ordered hexagonal arrays with the density amplification up by a factor of 17, within the minimally patterned trench surfaces of 100 MUm by 100 MUm. Furthermore, we produced line patterns of cylindrical microdomains by using solvent vapor annealing on the minimally patterned trench surfaces. However, highly aligned line patterns could be achieved only on the patterned surface with P = 5.75L0, W = 1.26L0, and D = 0.30L0 because the influence of the minimally patterned trench surface on the lateral ordering decreased as the P and W increase at the fixed D, resulting in poor ordering. These findings suggest that the minimal topographic pattern is more effective in guiding hexagonal arrays than in guiding line patterns. PMID- 27391373 TI - Design, Synthesis, and Identification of 4"alpha-Azidoethyl-cyclic ADP Carbocyclic-ribose as a Highly Potent Analogue of Cyclic ADP-Ribose, a Ca(2+) Mobilizing Second Messenger. AB - Cyclic adenosine diphosphate-carbocyclic-ribose (cADPcR, 2) is a stable equivalent of cyclic adenosine diphosphate-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. On the basis of the structure-activity relationship of cADPR related compounds and three-dimensional structural modeling of cADPcR, we designed and synthesized cyclic-ADP-4"alpha-azidoethyl carbocyclic-ribose (N3 cADPcR, 3) to demonstrate that it has a highly potent Ca(2+)-mobilizing activity (EC50 = 24 nM). N3-cADPcR will be a useful precursor for the preparation of biological tools effective to investigate cADPR-mediated signaling pathways. PMID- 27391374 TI - Synthesis of Benzo[a]carbazoles and an Indolo[2,3-a]carbazole from 3-Aryltetramic Acids. AB - A simple and flexible approach to 3-pyrrolin-2-one fused carbazoles is disclosed. The key step involves the BF3-mediated electrophilic substitution of indoles with N-alkyl-substituted 3-aryltetramic acids, which provides access to indole substituted 3-pyrrolin-2-ones. Scholl-type oxidative cyclizations of these materials led to the formation of the corresponding 3-pyrrolin-2-one-fused benzo[a]carbazoles and indolo[2,3-a]carbazoles. This work represents the first synthesis of the benzo[a]pyrrolo[3,4-c]carbazol-3(8H)-one ring system, while the indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one ring system is found in a number of biologically active compounds including the protein kinase C (PKC) inhibitor, staurosporine. PMID- 27391371 TI - Internet use by patients with bipolar disorder: Results from an international multisite survey. AB - There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar disorder in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important. PMID- 27391375 TI - Characterization of lipid-rich plaques using spectroscopic optical coherence tomography. AB - Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the internal structures of walls of coronary arteries in vivo. However, accurate characterization of atherosclerotic plaques with gray scale IV-OCT images is often limited by various intrinsic artifacts. In this study, we present an algorithm for characterizing lipid-rich plaques with a spectroscopic OCT technique based on a Gaussian center of mass (GCOM) metric. The GCOM metric, which reflects the absorbance properties of lipids, was validated using a lipid phantom. In addition, the proposed characterization method was successfully demonstrated in vivo using an atherosclerotic rabbit model and was found to have a sensitivity and specificity of 94.3% and 76.7% for lipid classification, respectively. PMID- 27391376 TI - Coherent anti-Stokes Raman scattering hyperspectral imaging of cartilage aiming for state discrimination of cell. AB - Noninvasive cell analyses are increasingly important in the medical field. A coherent anti-Stokes Raman scattering (CARS) microscope is the noninvasive imaging equipment and enables to obtain images indicating molecular distribution. However, due to low-signal intensity, it is still challenging to obtain images of the fingerprint region, in which many spectrum peaks correspond to compositions of a cell. Here, to identify cell differentiation by using multiplex CARS, we investigated hyperspectral imaging of the fingerprint region of living cells. To perform multiplex CARS, we used a prototype of a compact light source generating both pump light and broadband Stokes light. Assuming application to regenerative medicine, we chose a cartilage cell, whose differentiation is difficult to be identified by change of the cell morphology. Because one of the major components of cartilage is collagen, we focused on distribution of proline, which accounts for approximately 20% of collagen. The spectrum quality was improved by optical adjustments of the power branching ratio and divergence of Stokes light. Periphery of a cartilage cell was highlighted in a CARS image of proline, and this result suggests correspondence with collagen generated as an extracellular matrix. The possibility of noninvasive analyses by using CARS hyperspectral imaging was indicated. PMID- 27391377 TI - Genomewide miRNA profiling of oral lichenoid disorders and oral squamous cell carcinoma. AB - OBJECTIVE: To dissect the aberrant microRNA profile of oral lichenoid disorders (OLD) by analyzing the larger set of OLD samples tested so far. MATERIALS AND METHODS: MicroRNA expression profiles were assessed using TLDA card in 32 samples (16 OLD, 8 OSCC, and 8 control). The findings were validated using RT-qPCR in an independent cohort of 91 samples. RESULTS: We identified 20 differentially expressed microRNAs in OLD, of which several are functionally related to cell proliferation, response to organic substances, or immune processes. Further validation of the top-ranked microRNAs revealed that they were all aberrantly expressed in OLD. CONCLUSION: We have identified a new microRNA signature associated with OLD that may provide a meaningful basis for better understanding the physiopathology of the disease. In addition, we validated seven microRNAs whose expression was shown to be higher in OLD tissue in comparison with the control and OSCC tissues. PMID- 27391379 TI - Imaging and Clinical Outcomes in 20 Dogs Treated with Thin Film Banding for Extrahepatic Portosystemic Shunts. AB - OBJECTIVE: To prospectively evaluate the efficacy of thin film band attenuation of congenital extrahepatic portosystemic shunts (CEPSS) in dogs using clinical, biochemical, and imaging-related outcome measures. STUDY DESIGN: Prospective case series. ANIMALS: Dogs with CEPSS (n=20). METHODS: Client-owned dogs with CEPSS were enrolled and thin film banding of the shunting vessel was performed. Before and at least 6 months after surgery, serum bile acids and computed tomography (CT) angiography were performed and owners completed a health questionnaire regarding the dog's clinical signs. Postoperative CT images were assessed for the effectiveness of band closure, change in portal vein/aorta ratio, change in liver volume/weight ratio, and whether the band was placed in the appropriate location. Preoperative and postoperative health questionnaire data and serum bile acids were compared. RESULTS: The band resulted in complete closure of the vessel around which it was placed in 13 dogs. In the remaining 7 dogs, the vessel lumen was narrowed but not completely closed. In 8 dogs the band location was suboptimal, allowing systemic drainage of visceral blood or secondary shunting branches to persist. Liver volume/body weight ratios and portal vein/aorta diameter ratios increased in most dogs. Serum bile acids decreased in all but 1 dog and owners reported improved health in 19 dogs. CONCLUSION: Thin film banding resulted in complete occlusion of many, but not all vessels around which it was placed. Even in dogs with inappropriate band location or with incomplete closure, clinical improvement can be expected based on our results. PMID- 27391378 TI - Integrated palliative care in Europe: a qualitative systematic literature review of empirically-tested models in cancer and chronic disease. AB - BACKGROUND: Integrated Palliative Care (PC) strategies are often implemented following models, namely standardized designs that provide frameworks for the organization of care for people with a progressive life-threatening illness and/or for their (in)formal caregivers. The aim of this qualitative systematic review is to identify empirically-evaluated models of PC in cancer and chronic disease in Europe. Further, develop a generic framework that will consist of the basis for the design of future models for integrated PC in Europe. METHODS: Cochrane, PubMed, EMBASE, CINAHL, AMED, BNI, Web of Science, NHS Evidence. Five journals and references from included studies were hand-searched. Two reviewers screened the search results. Studies with adult patients with advanced cancer/chronic disease from 1995 to 2013 in Europe, in English, French, German, Dutch, Hungarian or Spanish were included. A narrative synthesis was used. RESULTS: 14 studies were included, 7 models for chronic disease, 4 for integrated care in oncology, 2 for both cancer and chronic disease and 2 for end-of-life pathways. The results show a strong agreement on the benefits of the involvement of a PC multidisciplinary team: better symptom control, less caregiver burden, improvement in continuity and coordination of care, fewer admissions, cost effectiveness and patients dying in their preferred place. CONCLUSION: Based on our findings, a generic framework for integrated PC in cancer and chronic disease is proposed. This framework fosters integration of PC in the disease trajectory concurrently with treatment and identifies the importance of employing a PC trained multidisciplinary team with a threefold focus: treatment, consulting and training. PMID- 27391381 TI - Career anchors of dentist leaders. AB - OBJECTIVE: The work of a health care leader is demanding; in order to cope, leaders need motivation and support. The occurrence of intrinsic factors called career anchors (combination of one's competence, motives and values) could be a contributing factor in dentist leaders' career decisions. The aim of our study was to identify dentist leaders' career anchors and their association to dentist leaders' retention or turnover of the leadership position. MATERIAL AND METHODS: Materials were gathered in 2014 via an electronic questionnaire from 156 current (Leaders) or former (Leavers) Finnish dentist leaders. Career anchor evaluation was conducted by the questionnaire and scoring-table taken from Edgar Schein's Career Anchors Self-Assessment. Both the most and the least important career anchors were detected by the highest and lowest scores and their occurrence reported as percentages. Associations between career anchor scores and tendency to stay were analyzed with logistic regression. RESULTS: 'Technical/Functional Competence' and 'Lifestyle' were most frequently reported as the most important and 'Entrepreneurial Creativity' and 'General Managerial Competence' as the least important career anchors. However, a higher level of 'General Managerial Competence' anchor was most significantly associated with staying in a leadership position. Instead, 'Pure Challenge' and 'Lifestyle' decreased the odds to stay. CONCLUSIONS: The knowledge of the important and essential career anchors of dentist leaders' and individuals' could perform crucial part in career choices and also in planning education, work opportunities and human resource policies promoting retention of dentist leaders and probably also other health care leaders. PMID- 27391382 TI - Interface Engineering To Boost Photoresponse Performance of Self-Powered, Broad Bandwidth PEDOT:PSS/Si Heterojunction Photodetector. AB - Organic-inorganic hybrid heterojunctions are poised to push toward novel optoelectronics applications, such as photodetectors, but significant challenges complicating practical use remain. Although all organic based photodetectors have been reported with great success, their potential in high-speed, broadband, self powered photodetectors have not been fully explored. Herein, a self-powered, broad bandwidth of photodetector based on PEDOT: PSS/Si heterojunction is built by a facial low temperature spin-coating method. By interface engineering of heterojunction with optimal band alignment and heteromicrostructures, enhanced photoresponse performances are obtained. The bandwidth of the hybrid photodetector could be broadened by 10 kHz after interfacial passivation by a methyl group. Further manipulating the geometrical structure of the hybrid heterojunction with silicon nanowire, a broad spectrum response from 300 to 1100 nm, with bandwidth as high as 40.6 kHz, fast response speed of 2.03 MUs and high detection of 4.1 * 10(11) Jones under zero bias was achieved. Meanwhile, the close dependence between the photoresponse performance of heterojunctions and Si nanowire length is observed in the top-coverage configuration. Finally, a coverage effects model is proposed based on the competition of Si bulk and surface recombination, which is also confirmed by the designed bottom-coverage experiment. The mechanisms behind the enhanced photoresponse of the hybrid photodetector is attributed to the optimum band alignment, as well as the optimum balance of carrier dissociation and recombination of heterojunction. The scalable and low temperature method would be of great convenience for large-scale fabrication of the PEDOT: PSS/Si hybrid photodetector. PMID- 27391380 TI - Tear gas: an epidemiological and mechanistic reassessment. AB - Deployments of tear gas and pepper spray have rapidly increased worldwide. Large amounts of tear gas have been used in densely populated cities, including Cairo, Istanbul, Rio de Janeiro, Manama (Bahrain), and Hong Kong. In the United States, tear gas was used extensively during recent riots in Ferguson, Missouri. Whereas tear gas deployment systems have rapidly improved-with aerial drone systems tested and requested by law enforcement-epidemiological and mechanistic research have lagged behind and have received little attention. Case studies and recent epidemiological studies revealed that tear gas agents can cause lung, cutaneous, and ocular injuries, with individuals affected by chronic morbidities at high risk for complications. Mechanistic studies identified the ion channels TRPV1 and TRPA1 as targets of capsaicin in pepper spray, and of the tear gas agents chloroacetophenone, CS, and CR. TRPV1 and TRPA1 localize to pain-sensing peripheral sensory neurons and have been linked to acute and chronic pain, cough, asthma, lung injury, dermatitis, itch, and neurodegeneration. In animal models, transient receptor potential inhibitors show promising effects as potential countermeasures against tear gas injuries. On the basis of the available data, a reassessment of the health risks of tear gas exposures in the civilian population is advised, and development of new countermeasures is proposed. PMID- 27391383 TI - Identification of a novel HLA-A*02 allele, HLA-A*02:622N. AB - HLA-A*02:622N differs from A*02:07:01 by a single nucleotide substitution at position 420 of exon 3. PMID- 27391386 TI - The safety and efficacy of benzbromarone in gout in Aotearoa New Zealand. AB - BACKGROUND: Benzbromarone is a potent uricosuric but is not widely available due to concerns about hepatotoxicity. In Aotearoa New Zealand, benzbromarone has been available since April 2013, subject to funding restrictions, for patients with inadequate urate-lowering response or intolerance to allopurinol and probenecid. AIM: To assess the safety and efficacy of benzbromarone in a real-life setting. METHODS: All patients who received funding for benzbromarone from 1 April 2013 to 30 September 2014 were identified. Prescribers were sent a questionnaire for each individual. Information on demographics, efficacy of previous urate-lowering drugs and reasons for discontinuation were collected. Specific information about the dose, effect on serum urate, adverse effects and liver function tests after commencing benzbromarone was recorded. RESULTS: Completed questionnaires were returned for 123 of 164 (75%) patients. Mean (SD) serum urate prior to benzbromarone was 0.57 (0.12) mmol/L, and estimated glomerular filtration rate was 50.3 (22.8) mL/min/1.73 m(2) . The median dose of benzbromarone was 100 mg/day (25-200 mg/day). Six months after commencing benzbromarone, mean (SD) serum urate was 0.35 (0.12) mmol/L. Benzbromarone-related adverse events included rash (n = 4), diarrhoea (n = 9), nausea (n = 6) and urate stones (n = 3). Liver function test abnormalities were uncommon and tended to be mild. There were 14 patient deaths; none was considered related to benzbromarone. Allopurinol had been prescribed prior to benzbromarone in 117 of 123 patients; median maximum allopurinol dose was 200 mg/day (range 25-600 mg/day), and 19% patients received allopurinol >300 mg/day. CONCLUSION: Benzbromarone provides useful urate-lowering efficacy and does not appear unsafe in patients with gout. Urate-lowering therapy prescribing requires further optimisation. PMID- 27391387 TI - Metabolic Syndrome After HIV Acquisition in South African Women. AB - BACKGROUND: Noncommunicable diseases are common among chronically infected patients with HIV in the developed world, but little is known about these conditions in African cohorts. We assessed the epidemiology of metabolic syndrome among young South African women during the first 3 years after HIV acquisition. METHODS: A total of 160 women were followed prospectively in the CAPRISA 002 Acute Infection study. Metabolic syndrome was defined as a constellation of hyperlipidemia, hypertension, hyperglycemia/diabetes, and abdominal obesity. Time trends were assessed using generalized estimation equation models. RESULTS: Median age was 24 years and body mass index 27 kg/m. Prevalence of metabolic syndrome at infection was 8.7% increasing to 19.2% over 36 months (P = 0.001). The proportion of women with body mass index >30 kg/m increased from 34.4% to 47.7% (P = 0.004), those with abnormal waist circumference and elevated blood pressure increased from 33.5% to 44.3% (P = 0.060) and 23.8% to 43.9% (P < 0.001), respectively. Incidence of metabolic syndrome was 9.13/100 person-years (95% CI: 6.02 to 13.28). Predictors of metabolic syndrome were age (per year increase odds ratio (OR) = 1.12; 95% CI: 1.07 to 1.16), time postinfection (per year OR = 1.47; 95% CI: 1.12 to 1.92), family history of diabetes (OR = 3.13; 95% CI: 1.71 to 5.72), and the human leukocyte antigen (HLA)-B*81:01 allele (OR = 2.95; 95% CI: 1.21 to 7.17), whereas any HLA-B*57 or B*58:01 alleles were protective (OR = 0.34; 95% CI: 0.15 to 0.77). HIV-1 RNA (OR = 0.89; 95% CI: 0.62 to 1.27) and CD4 count (OR = 1.03; 95% CI: 0.95 to 1.11) did not predict metabolic syndrome. CONCLUSIONS: The high burden of metabolic conditions in young South African HIV-infected women highlights the need to integrate noncommunicable disease and HIV care programs. Interventions to prevent cardiovascular disease must start at HIV diagnosis, rather than later during the disease course. PMID- 27391384 TI - Primary Human Uterine Leiomyoma Cell Culture Quality Control: Some Properties of Myometrial Cells Cultured under Serum Deprivation Conditions in the Presence of Ovarian Steroids. AB - Cell culture is considered the standard media used in research to emulate the in vivo cell environment. Crucial in vivo experiments cannot be conducted in humans and depend on in vitro methodologies such as cell culture systems. However, some procedures involving the quality control of cells in culture have been gradually neglected by failing to acknowledge that primary cells and cell lines change over time in culture. Thus, we report methods based on our experience for monitoring primary cell culture of human myometrial cells derived from uterine leiomyoma. We standardized the best procedure of tissue dissociation required for the study of multiple genetic marker systems that include species-specific antigens, expression of myofibroblast or myoblast markers, growth curve, serum deprivation, starvation by cell cycle synchronization, culture on collagen coated plates, and 17 beta-estradiol (E2) and progesterone (P4) effects. The results showed that primary myometrial cells from patients with uterine leiomyoma displayed myoblast phenotypes before and after in vitro cultivation, and leiomyoma cells differentiated into mature myocyte cells under the appropriate differentiation inducing conditions (serum deprivation). These cells grew well on collagen coated plates and responded to E2 and P4, which may drive myometrial and leiomyoma cells to proliferate and adhere into a focal adhesion complex involvement in a paracrine manner. The establishment of these techniques as routine procedures will improve the understanding of the myometrial physiology and pathogenesis of myometrium-derived diseases such as leiomyoma. Mimicking the in vivo environment of fibrotic conditions can prevent false results and enhance results that are based on cell culture integrity. PMID- 27391388 TI - Religion and HIV Sexual Risk Among Men Who Have Sex With Men in China. AB - BACKGROUND: Religion can profoundly impact the sociocultural contexts that shape sexual HIV vulnerability among men who have sex with men (MSM). However, the relationship between religion and HIV vulnerability remains poorly understood for MSM in China, where religious affiliations and practices are rapidly increasing. METHODS: Using cross-sectional survey data collected in Beijing and Tianjin, China, from 2013 to 2014 (n = 400), this study tests 3 hypotheses regarding religion and HIV sexual risk: (1) HIV vulnerabilities and testing patterns among religiously affiliated MSM are lower than for areligious MSM, (2) religiosity is inversely associated with HIV vulnerabilities and testing, and (3) the magnitude of inverse association between religiosity and HIV vulnerabilities/testing will be stronger among Christian and Muslim MSM than Buddhist and areligious MSM. RESULTS: Compared with areligious participants, Buddhists had higher odds of reporting unprotected anal intercourse [adjusted odds ratio (AOR): 2.06, 95% confidence interval (CI): 1.13 to 3.75] and more male sex partners (AOR: 1.95, 1.16-3.27), whereas Muslims had lower odds of reporting unprotected anal intercourse (AOR: 0.33, 95% CI: 0.15 to 0.73) and higher odds of reporting male circumcision (AOR: 3.04, 95% CI: 1.45 to 6.40). Reporting of forced sex was associated with more frequent participation in social religious activities (AOR: 1.25, 95% CI: 1.02 to 1.52) and private religious activities (AOR: 1.30, 95% CI: 1.04 to 1.61). Among Christians, participation in private religious activities was associated with lower odds of reporting anal intercourse (AOR: 0.49, 95% CI: 0.27 to 0.88). CONCLUSIONS: The sustained growth of multiple religious traditions in China appears to have important implications for HIV vulnerability among religious minority MSM. PMID- 27391389 TI - Trends in Racial and Ethnic Disparities in Antiretroviral Therapy Prescription and Viral Suppression in the United States, 2009-2013. AB - OBJECTIVES: To examine trends in racial/ethnic disparities in antiretroviral therapy (ART) prescription and viral suppression among HIV-infected persons in care, overall and among men who have sex with men (MSM), from 2009 to 2013. DESIGN: The Medical Monitoring Project (MMP) is a complex sample survey of HIV infected adults receiving medical care in the United States. METHODS: We used weighted interview and medical record data collected June 2009-May 2014 to estimate the prevalence of ART prescription and viral suppression among racial/ethnic groups overall and among MSM. RESULTS: We found significant increases in ART prescription and viral suppression among all racial/ethnic groups from 2009 to 2013, both overall and among MSM. By 2013, overall and among MSM, the Hispanic-white disparity in ART prescription was nonexistent, and the black-white disparity was not significant after accounting for differences between blacks and whites in age and length of HIV diagnosis. Despite reductions in racial/ethnic disparities in viral suppression over the time period, significant disparities remained among the total population, even after adjusting for differences in racial/ethnic group characteristics. Encouragingly, however, there was no significant Hispanic-white disparity in viral suppression among MSM by 2013. CONCLUSIONS: Despite significant improvements in ART prescription and viral suppression in recent years, racial and ethnic disparities persist, particularly for black persons. If the United States is to achieve the National HIV/AIDS Strategy goal of reducing HIV-related health disparities, continued efforts to accelerate the rate of improvement in ART prescription and viral suppression among Hispanic and black persons may need to be prioritized. PMID- 27391390 TI - An fMRI Investigation of Preparatory Set in the Human Cerebral Cortex and Superior Colliculus for Pro- and Anti-Saccades. AB - Previous studies have identified several cortical regions that show larger BOLD responses during preparation and execution of anti-saccades than pro-saccades. We confirmed this finding with a greater BOLD response for anti-saccades than pro saccades during the preparation phase in the FEF, IPS and DLPFC and in the FEF and IPS in the execution phase. We then applied multi-voxel pattern analysis (MVPA) to establish whether different neural populations are involved in the two types of saccade. Pro-saccades and anti-saccades were reliably decoded during saccade execution in all three cortical regions (FEF, DLPFC and IPS) and in IPS during saccade preparation. This indicates neural specialization, for programming the desired response depending on the task rule, in these regions. In a further study tailored for imaging the superior colliculus in the midbrain a similar magnitude BOLD response was observed for pro-saccades and anti-saccades and the two saccade types could not be decoded with MVPA. This was the case both for activity related to the preparation phase and also for that elicited during the execution phase. We conclude that separate cortical neural populations are involved in the task-specific programming of a saccade while in contrast, the SC has a role in response preparation but may be less involved in high-level, task specific aspects of the control of saccades. PMID- 27391391 TI - The effectiveness of intra-aortic balloon pump for myocardial infarction in patients with or without cardiogenic shock: a meta-analysis and systematic review. AB - BACKGROUND: Conflicting reports on the efficacy of intra-aortic balloon pump (IABP) during percutaneous coronary intervention (PCI) incited us to evaluate the utility of IABP in patients with acute myocardial infarction (AMI). METHODS: Randomized clinical trials comparing patients, who received IABP vs. control (no IABP) during PCI, were hand-searched from MEDLINE, Cochrane, and EMBASE databases using the terms "intra-aortic balloon pump, percutaneous coronary intervention, myocardial infarction, acute coronary syndrome". Mortality rate (30-day and 6 month mortality) was the primary outcome, while the secondary outcomes included 30-day bleeding rate, reinfarction rate, revascularization rate and stroke rate. RESULTS: Pooled results of the seven trials identified indicated that the 30-day and 6-month mortality rate were not significantly different between the IABP and control groups. However, in patients with MI, but without cardiogenic shock (CS), IABP was associated with lower odds of 30-day mortality (OR = 0.35, p = 0.015) and 6-month mortality (OR = 0.41, p = 0.020). The pooled results of 30-day bleeding rate was not significantly higher in patients with IABP than the control group, but for the patients with high risk PCI without CS, it was higher in patients with IABP than the control group (OR = 1.58, p = 0.009). The re infarction, revascularization, and the stroke rate at 30 days of follow-up were not significantly different between the two groups. CONCLUSIONS: The present results do not favor the clinical utility of IABP in patients suffering high-risk PCI without CS and AMI complicated with CS. However, in patients with AMI, but without CS, IABP may reduce the 30-day and 6-month mortality rate. PMID- 27391393 TI - alpha-Amidino Rhodium Carbenes: Key Intermediates for the Preparation of (E)-2 Aminomethylene-3-oxoindoles and Pyranoindoles. AB - Rhodium-catalyzed reactions of 3-diazoindolin-2-imines with aromatic aldehydes and alpha,beta-unsaturated aldehydes respectively furnished (E)-2-aminomethylene 3-oxoindoles and pyranoindoles in moderate to excellent yields with nice functional group tolerance. The reaction proceeds in a cascade involving alpha amidino rhodium carbene as the key intermediate. PMID- 27391392 TI - Characterization of the pigment fraction in sweet bell peppers (Capsicum annuum L.) harvested at green and overripe yellow and red stages by offline multidimensional convergence chromatography/liquid chromatography-mass spectrometry. AB - Offline multidimensional supercritical fluid chromatography combined with reversed-phase liquid chromatography was employed for the carotenoid and chlorophyll characterization in different sweet bell peppers (Capsicum annuum L.) for the first time. The first dimension consisted of an Acquity HSS C18 SB (100 * 3 mm id, 1.8 MUm particles) column operated with a supercritical mobile phase in an ultra-performance convergence chromatography system, whereas the second dimension was performed in reversed-phase mode with a C30 (250 * 4.6 mm id, 3.0 MUm particles) stationary phase combined with photodiode array and mass spectrometry detection. This approach allowed the determination of 115 different compounds belonging to chlorophylls, free xanthophylls, free carotenes, xanthophyll monoesters, and xanthophyll diesters, and proved to be a significant improvement in the pigments determination compared to the conventional one dimensional liquid chromatography approach so far applied to the carotenoid analysis in the studied species. Moreover, the present study also aimed to investigate and to compare the carotenoid stability and composition in overripe yellow and red bell peppers collected directly from the plant, thus also evaluating whether biochemical changes are linked to carotenoid degradation in the nonclimacteric investigated fruits, for the first time. PMID- 27391394 TI - Cation-Selective and Anion-Controlled Fluorogenic Behaviors of a Benzothiazole Attached Macrocycle That Correlate with Structural Coordination Modes. AB - We report how the metal cation and its counteranions cooperate in the complexation-based macrocyclic chemosensor to monitor the target metal ion via the specific coordination modes. The benzothiazolyl group bearing NO2S2 macrocycle L was synthesized, and its mercury(II) selectivity (for perchlorate salt) as a dual-probe channel (UV-vis and fluorescence) chemosensor exhibiting the largest blue shift and the fluorescence turn-off was observed. In the mercury(II) sensing with different anions, except ClO4(-) and NO3(-), no responses for mercury(II) were observed with other anions such as Cl(-), Br(-), I(-), SCN(-), OAc(-), and SO4(2-). A crystallographic approach for the mononuclear mercury(II) perchlorate complex [Hg(L)(ClO4)2].0.67CH2Cl2 (1) and polymeric mercury(II) iodide complex [Hg(L)I2]n (2) revealed that the observed anion-controlled mercury(II) sensing in the fluorescence mainly stems from the endo- and exocoordination modes, depending on the anion coordinating ability, which induces either the Hg-Ntert bond formation or not. The detailed complexation process with mercury(II) perchlorate associated with the cation sensing was also monitored with the titration methods by UV-vis, fluorescence spectroscopy, and cold-spray ionization mass spectrometry. PMID- 27391395 TI - Letter to the Editor: The effect of methylene blue on postoperative low-back pain. PMID- 27391396 TI - Radiographic feasibility study of cortical bone trajectory and traditional pedicle screw dual trajectories. AB - OBJECTIVE In 2009, Santoni and colleagues described a novel technique of posterior instrumentation; the cortical bone trajectory (CBT) was described as a caudocephalad and medial-to-lateral trajectory. Reported indications for CBT fixation include patients with osteoporosis, single-level degenerative disease, or adjacent-segment disease (ASD). In cases of revision surgery, it is technically possible and beneficial to place a traditional pedicle screw and a CBT screw at the same spinal level and side. It remains unclear as to the feasibility of placing both a traditional and a CBT screw at all levels of the lumbar spine and with varying trajectories of the preexisting traditional pedicle screws. Therefore, the authors conducted a study to radiographically assess the feasibility of using CBT and traditional pedicle screws at the same level in a large patient population. METHODS Using a 3D Spine Navigation WorkStation, the authors assessed 47 lumbar spine CT scans. These images were obtained from 2 disparate groups of patients: those who had previously undergone traditional pedicle instrumentation (prior surgery group) and those who had not (no prior surgery group). The authors virtually placed traditional pedicle and CBT screws at each lumbar level bilaterally. It was then determined if the dual trajectories were feasible, as defined by the presence or absence of a collision of the screw trajectories based on 3D imaging. RESULTS Overall, the authors evaluated 47 patients and were able to successfully plan dual trajectories in 50% of the pedicles. The no prior surgery group, compared with the prior surgery group, had a significantly greater success rate for dual trajectories. This difference was most significant in the lower lumbar levels (L3-5) where the prior instrumented group had success rates lower than 40% compared with the no prior surgery group's success rate, which was greater than 70%. There was a significant difference between each lumbar level in the lower spine. CONCLUSIONS There is a significant difference in the feasibility of planning CBT screws in patients who have undergone prior pedicle instrumentation compared with placing CBT and traditional pedicle screws simultaneously, but dual trajectory pedicle screws are a feasible option for posterior lumbar spinal instrumentation, especially as a de novo option in osteoporotic patients or in patients with ASD who underwent previous pedicle instrumentation. Ultimately, the practical clinical utility and biomechanical effects on the spine and instrumentation construct would require additional study. PMID- 27391397 TI - Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma. AB - OBJECT Systemic control of metastatic renal cell carcinoma (mRCC) has substantially improved with the development of VEGF, mTOR, and checkpoint inhibitors. The current first-line standard of care is a VEGF tyrosine kinase inhibitor (TKI). In preclinical models, TKIs potentiate the response to radiotherapy. Such improved efficacy may prolong the time to salvage therapies, including whole-brain radiotherapy or second-line systemic therapy. As the prevalence of mRCC has increased, the utilization of spine stereotactic radiosurgery (SRS) has also increased. However, clinical outcomes following concurrent treatment with SRS and TKIs remain largely undefined. The purpose of this investigation was to determine the safety and efficacy of TKIs when delivered concurrently with SRS. The authors hypothesized that first-line TKIs delivered concurrently with SRS significantly increase local control compared with SRS alone or TKIs alone, without increased toxicity. METHODS A retrospective cohort study of patients undergoing spine SRS for mRCC was conducted. Patients undergoing SRS were divided into 4 cohorts: those receiving concurrent first-line TKI therapy (A), systemic therapy-naive patients (B), and patients who were undergoing SRS with (C) or without (D) concurrent TKI treatment after failure of first-line therapy. A negative control cohort (E) was also included, consisting of patients with spinal metastases managed with TKIs alone. The primary outcome was 12-month local failure, defined as any in-field radiographic progression. Multivariate competing risks regression was used to determine the independent effect of concurrent first-line TKI therapy upon local failure. RESULTS One hundred patients who underwent 151 spine SRS treatments (232 vertebral levels) were included. At the time of SRS, 46% were receiving concurrent TKI therapy. In each SRS cohort, the median prescription dose was 16 Gy in 1 fraction. Patients in Cohort A had the highest burden of epidural disease (96%, p < 0.01). At 12 months, the cumulative incidence of local failure was 4% in Cohort A, compared with 19%-27% in Cohorts B-D and 57% in Cohort E (p < 0.01). Multivariate competing risks regression demonstrated that concurrent first-line TKI treatment (Cohort A) was independently associated with a local control benefit (HR 0.21, p = 0.04). In contrast, patients treated with TKIs alone (Cohort E) experienced an increased rate of local failure (HR 2.43, p = 0.03). No toxicities of Grade 3 or greater occurred following SRS with concurrent TKI treatment, and the incidence of post-SRS vertebral fracture (overall 21%) and pain flare (overall 17%) were similar across cohorts. CONCLUSIONS The prognosis for patients with mRCC has significantly improved with TKIs. The present investigation suggests a local control benefit with the addition of concurrent first-line TKI therapy to spine SRS. These results have implications in the oligometastatic setting and support a body of preclinical radiobiological research. PMID- 27391398 TI - Biomechanical evaluation of lateral lumbar interbody fusion with secondary augmentation. AB - OBJECTIVE Lateral lumbar interbody fusion (LLIF) has emerged as a popular method for lumbar fusion. In this study the authors aimed to quantify the biomechanical stability of an interbody implant inserted using the LLIF approach with and without various supplemental fixation methods, including an interspinous plate (IP). METHODS Seven human cadaveric L2-5 specimens were tested intact and in 6 instrumented conditions. The interbody implant was intended to be used with supplemental fixation. In this study, however, the interbody was also tested without supplemental fixation for a relative comparison of these conditions. The instrumented conditions were as follows: 1) interbody implant without supplemental fixation (LLIF construct); and interbody implant with supplemental fixation performed using 2) unilateral pedicle screws (UPS) and rod (LLIF + UPS construct); 3) bilateral pedicle screws (BPS) and rods (LLIF + BPS construct); 4) lateral screws and lateral plate (LP) (LLIF + LP construct); 5) interbody LP and IP (LLIF + LP + IP construct); and 6) IP (LLIF + IP construct). Nondestructive, nonconstraining torque (7.5 Nm maximum) induced flexion, extension, lateral bending, and axial rotation, whereas 3D specimen range of motion (ROM) was determined optoelectronically. RESULTS The LLIF construct reduced ROM by 67% in flexion, 52% in extension, 51% in lateral bending, and 44% in axial rotation relative to intact specimens (p < 0.001). Adding BPS to the LLIF construct caused ROM to decrease by 91% in flexion, 82% in extension and lateral bending, and 74% in axial rotation compared with intact specimens (p < 0.001), providing the greatest stability among the constructs. Adding UPS to the LLIF construct imparted approximately one-half the stability provided by LLIF + BPS constructs, demonstrating significantly smaller ROM than the LLIF construct in all directions (flexion, p = 0.037; extension, p < 0.001; lateral bending, p = 0.012) except axial rotation (p = 0.07). Compared with the LLIF construct, the LLIF + LP had a significant reduction in lateral bending (p = 0.012), a moderate reduction in axial rotation (p = 0.18), and almost no benefit to stability in flexion extension (p = 0.86). The LLIF + LP + IP construct provided stability comparable to that of the LLIF + BPS. The LLIF + IP construct provided a significant decrease in ROM compared with that of the LLIF construct alone in flexion and extension (p = 0.002), but not in lateral bending (p = 0.80) and axial rotation (p = 0.24). No significant difference was seen in flexion, extension, or axial rotation between LLIF + BPS and LLIF + IP constructs. CONCLUSIONS The LLIF construct that was tested significantly decreased ROM in all directions of loading, which indicated a measure of inherent stability. The LP significantly improved the stability of the LLIF construct in lateral bending only. Adding an IP device to the LLIF construct significantly improves stability in sagittal plane rotation. The LLIF + LP + IP construct demonstrated stability comparable to that of the gold standard 360 degrees fixation (LLIF + BPS). PMID- 27391399 TI - Subdural fluid collection and hydrocephalus following cervical schwannoma resection: hydrocephalus resolution after spinal pseudomeningocele repair: case report. AB - The authors report the case of a 31-year-old man who developed neck pain and headache 2 months after the uncomplicated resection of a cervical schwannoma. MR imaging revealed infratentorial subdural fluid collections and obstructive hydrocephalus associated with cervical pseudomeningocele. The clinical symptoms, subdural fluid collections, and ventricular dilation resolved after surgical correction of the pseudomeningocele. This report emphasizes that hydrocephalus may be related to disorders of cerebrospinal fluid flow dynamics induced by cervical pseudomeningocele. In these rare cases, both the hydrocephalus and the symptoms are resolved by the simple correction of the pseudomeningocele. PMID- 27391400 TI - Anterior hyperlordotic cages: early experience and radiographic results. AB - OBJECTIVE The aim of this study was to evaluate the segmental correction obtained from 20 degrees and 30 degrees hyperlordotic cages (HLCs) used for anterior lumbar interbody fusion in staged anterior and posterior fusion in adults with degenerative spinal pathology and/or spinal deformities. METHODS The authors report a retrospective case series of 69 HLCs in 41 patients with adult degenerative spine disease and/or deformities who underwent staged anterior, followed by posterior, instrumentation and fusion. There were 29 females and 12 males with a mean age of 55 years (range 23-76 years). The average follow-up was 10 months (range 2-28 months). Radiographic measurements of segmental lordosis and standard sagittal parameters were obtained on pre- and postoperative radiographs. Implant subsidence was measured at the final postoperative follow up. RESULTS For 30 degrees HLCs, the mean segmental lordosis achieved was 29 degrees (range 26 degrees -34 degrees ), but in the presence of spondylolisthesis this was reduced to 19 degrees (range 12 degrees -21 degrees ) (p < 0.01). For 20 degrees HLCs, the mean segmental lordosis achieved was 19 degrees (range 16 degrees -22 degrees ). The overall mean lumbar lordosis increased from 39 degrees to 59 degrees (p < 0.01). The mean sagittal vertical axis (SVA) reduced from 113 mm (range 38-320 mm) to 43 mm (range -13 to 112 mm). Six cages (9%) displayed a loss of segmental lordosis during follow-up. The mean loss of segmental lordosis was 4.5 degrees (range 3 degrees -10 degrees ). A total complication rate of 20% with a 4.1% transient neurological complication rate was observed. The mean blood loss per patient was 240 ml (range 50-900 ml). CONCLUSIONS HLCs provide a reliable and stable degree of segmental lordosis correction. A 30 degrees HLC will produce correction of a similar magnitude to a pedicle subtraction osteotomy, but with a lower complication rate and less blood loss. PMID- 27391401 TI - An orphan disease: IgG4-related spinal pachymeningitis: report of 2 cases. AB - IgG4-related disease is relatively new disease entity and a rare one, and our knowledge of this entity continues to evolve. It was first described in the pancreas and since then has been described in virtually every organ. Spinal involvement resulting in pachymeningitis is rare, and there are only 8 reported cases of the same to date, with the cervicothoracic spine being the most commonly affected region. The authors describe 2 cases in which the patients presented with spinal compression resulting in myeloradiculopathy (Case 1) and radiculopathy (Case 2). Imaging of spine in both cases revealed an ill-defined contrast-enhancing lesion at the lumbar level. Preoperatively, a diagnosis of spinal tumor was made, but intraoperatively no spinal tumor was found. The diagnosis was established histopathologically. The disease has no particular defining features clinically or radiologically and can mimic common spinal tumors. It is important to accurately diagnose this rare entity because of its multisystem involvement and progressive course. Strict treatment guidelines have yet to be formulated. Although histologically this disease can mimic other inflammatory conditions, the presence of storiform fibrosis and an increased number of IgG4-positive plasma cells can help in clarifying the diagnosis. PMID- 27391403 TI - Sacral bone mineral density (BMD) assessment using opportunistic CT scans. AB - This study seeks to establish a method for opportunistic evaluation of sacral bone mineral density. This is a retrospective review of 109 scans from 109 patients who had renal-protocol computed tomography (CT) scans performed for any indication during a 3-month period at a single academic institution in 2014. In the collected CT scans, sacral CT-attenuation in multiple regions of interest (ROI) was compared to the L1 CT-attenuation, an internal reference standard, to determine if a correlation existed. The sacral ROI were analyzed to determine regions of higher and lower attenuation. All sacral ROI had strong correlations with lumbar spine attenuation values, and these values became even stronger when transitional vertebrae were excluded. Sacral attenuation values varied predictably by location, and matched relationships were shown by prior volumetric bone mineral density studies. We conclude that sacral CT-attenuation can be used in opportunistic CT scans to determine sacral bone mineral density. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:160-166, 2017. PMID- 27391402 TI - Assessment of free fatty acids and cholesteryl esters delivered in liposomes as novel class of antibiotic. AB - BACKGROUND: Healthcare associated infections (HAI) with multidrug-resistant (MDR) bacteria continue to be a global threat, highlighting an urgent need for novel antibiotics. In this study, we assessed the potential of free fatty acids and cholesteryl esters that form part of the innate host defense as novel antibacterial agents for use against MDR bacteria. METHODS: Liposomes of six different phospholipid mixtures were employed as carrier for six different fatty acids and four different cholesteryl esters. Using a modified MIC assay based on DNA quantification with the fluoroprobe Syto9, formulations were tested against Gram-positive and Gram-negative bacteria implicated in HAI. Formulations with MIC values in the low MUg/mL range were further subjected to determination of minimal bactericidal activity, hemolysis assay with sheep erythrocytes, and cytotoxicity testing with the human liver cell line HepG2. The potential for synergistic activity with a standard antibiotic was also probed. RESULTS: Palmitic acid and stearic acid prepared in carrier 4 (PA4 and SA4, respectively) were identified as most active lipids (MIC against MDR Staphylococcus epidermidis was 0.5 and 0.25 MUg/mL, respectively; MIC against vancomycin resistant Enterococcus faecalis (VRE) was 2 and 0.5 MUg/mL, respectively). Cholesteryl linoleate formulated with carrier 3 (CL3) exhibited activity against the S. epidermidis strain (MIC 1 MUg/mL) and a Pseudomonas aeruginosa strain (MIC 8 MUg/mL) and lowered the vancomycin MIC for VRE from 32-64 MUg/mL to as low as 4 MUg/mL. At 90 MUg/mL PA4, SA4, and CL3 effected less than 5 % hemolysis over 3 h and PA4 and CL3 did not exhibit significant cytotoxic activity against HepG2 cells when applied at 100 MUg/mL over 48 h. CONCLUSIONS: Our results showed that selected fatty acids and cholesteryl esters packaged with phospholipids exhibit antibacterial activity against Gram-positive and Gram-negative bacteria and may augment the activity of antibiotics. Bactericidal activity could be unlinked from hemolytic and cytotoxic activity and the type of phospholipid carrier greatly influenced the activity. Thus, fatty acids and cholesteryl esters packaged in liposomes may have potential as novel lipophilic antimicrobial agents. PMID- 27391405 TI - Low-Toxicity Photopolymer for Reflection Holography. AB - A novel composition for a low-toxicity, water-soluble, holographic photopolymer capable of recording bright reflection gratings with diffraction efficiency of up to 50% is reported. The unique combination of two chemical components, namely, a chain transfer agent and a free radical scavenger, is reported to enhance the holographic recording ability of a diacetone acrylamide (DA)-based photopolymer in reflection mode by 3-fold. Characterization of the dependence of diffraction efficiency of the reflection gratings on spatial frequency, recording intensity, exposure energy, and recording wavelength has been carried out for the new low toxicity material. The use of UV postexposure as a method of improving the stability of the photopolymer-based reflection holograms is reported. The ability of the modified DA photopolymer to record bright Denisyuk holograms which are viewable in different lighting conditions is demonstrated. PMID- 27391404 TI - DNA-Catalyzed Introduction of Azide at Tyrosine for Peptide Modification. AB - We show that DNA enzymes (deoxyribozymes) can introduce azide functional groups at tyrosine residues in peptide substrates. Using in vitro selection, we identified deoxyribozymes that transfer the 2'-azido-2'-deoxyadenosine 5' monophosphoryl group (2'-Az-dAMP) from the analogous 5'-triphosphate (2'-Az-dATP) onto the tyrosine hydroxyl group of a peptide, which is either tethered to a DNA anchor or free. Some of the new deoxyribozymes are general with regard to the amino acid residues surrounding the tyrosine, while other DNA enzymes are sequence-selective. We use one of the new deoxyribozymes to modify free peptide substrates by attaching PEG moieties and fluorescent labels. PMID- 27391406 TI - Protocol of a mixed method, randomized controlled study to assess the efficacy of a psychosocial intervention to reduce fatigue in patients with End-Stage Renal Disease (ESRD). AB - BACKGROUND: Patients with end-stage renal disease (ESRD) commonly suffer from severe fatigue, which strongly impacts their quality of life (QoL). Although fatigue is often attributed to disease- and treatment characteristics, research also shows that behavioural, psychological and social factors affect perceived fatigue in dialysis patients. Whereas studies on fatigue in other chronic patient groups suggest that psychological or psychosocial interventions are effective in reducing fatigue, such interventions are not yet available for ESRD patients on dialysis treatment. The objective of this study is to examine the efficacy of a psychosocial intervention for dialysis patients aimed at reducing fatigue (primary outcome) and improving QoL (secondary outcome). The intervention consists of counselling sessions led by a social worker. The implementation process and patients' and social workers' expectations and experiences with the intervention will also be evaluated. METHODS/DESIGN: This study follows a mixed methods design in which both quantitative and qualitative data will be collected. A multi-centre, randomised controlled trial (RCT) with repeated measures will be conducted to quantitatively assess the efficacy of the psychosocial intervention in reducing fatigue and improving QoL in ESRD patients. Additional secondary outcomes and medical parameters will be assessed. Outcomes will be compared to patients receiving usual care. A sample of 74 severely fatigued dialysis patients will be recruited from 10 dialysis centres. Patients will be randomly assigned to the intervention or control group. Outcomes will be assessed at baseline, post intervention/16 weeks, and at three and six-month follow-ups. A qualitative process evaluation will be conducted parallel to/following the effectiveness RCT. Interviews and focus groups will be conducted to gain insight into patients' and social workers' perspectives on outcomes and implementation procedures. Implementation fidelity will be assessed by audio-taped and written registrations. Participatory methods ensure the continuous input of experiential knowledge, improving the quality of study procedures and the applicability of outcomes. DISCUSSION: This is the first mixed method study (including an RCT and qualitative process evaluation) to examine the effect and implementation process of a psychosocial intervention on reducing fatigue and improving QoL in ESRD patients on dialysis treatment. TRIAL REGISTRATION: NTR5366 , The Netherlands National Trial Register (NTR), registered August 26, 2015. PMID- 27391407 TI - Exposure to environmental factors increases connectivity between symptom domains in the psychopathology network. AB - BACKGROUND: We investigated to what degree environmental exposure (childhood trauma, urbanicity, cannabis use, and discrimination) impacts symptom connectivity using both continuous and categorical measures of psychopathology. METHODS: Outcomes were continuous symptom dimensions of self-reported psychopathology using the Self-report Symptom Checklist-90-R in 3021 participants from The Early Developmental Stages of the Psychopathology (EDSP) study and binary DSM-III-R categories of mental disorders and a binary measure of psychotic symptoms in 7076 participants from The Netherlands Mental Health Survey and Incidence Study (NEMESIS-1). For each symptom dimension in the EDSP and mental disorder in the NEMESIS-1 as the dependent variable, regression analyses were carried out including each of the remaining symptom dimensions/mental disorders and its interaction with cumulative environmental risk load (the sum score of environmental exposures) as independent variables. RESULTS: All symptom dimensions in the EDSP and related diagnostic categories in the NEMESIS-1 were strongly associated with each other, and environmental exposures increased the degree of symptom connectivity in the networks in both cohorts. CONCLUSIONS: Our findings showing strong connectivity across symptom dimensions and related binary diagnostic constructs in two independent population cohorts provide further evidence for the conceptualization of psychopathology as a contextually sensitive network of mutually interacting symptoms. PMID- 27391409 TI - Influence of acute stress on decision outcomes and heuristics. AB - BACKGROUND: The purpose of this study was to examine the take-the-first (TTF) heuristic and decision outcomes in sports under conditions of no, mental, and physical stress. METHODS: Participants (N.=68) performed 8 video decision-making trials under each of 3 stress conditions: no stress (counting backwards), mental stress (mental serial subtraction), and physical stress (running on treadmill at 13 RPE). Prior to each decision-making trial, participants were exposed to 30 seconds of stress. The decision-making task required participants to watch a video depicting an offensive situation in basketball and then decide what the player with the ball should do next. RESULTS: No differences were found between the 3 stress conditions on TTF frequency, number of options generated, quality of first generated option, or final decision quality. However, participants performing under conditions of no stress and physical stress generated their first option and made their final decision faster than they did when making decisions under mental stress. CONCLUSIONS: Overall, results suggest that mental stress impairs decision speed and that TTF is an ecologically rationale heuristic in dynamic, time-pressured situations. PMID- 27391408 TI - SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair. AB - SQSTM1/p62 (sequestosome 1) selectively targets polyubiquitinated proteins for degradation via macroautophagy and the proteasome. Additionally, SQSTM1 shuttles between the cytoplasmic and nuclear compartments, although its role in the nucleus is relatively unknown. Here, we report that SQSTM1 dynamically associates with DNA damage foci (DDF) and regulates DNA repair. Upon induction of DNA damage SQSTM1 interacts with FLNA (filamin A), which has previously been shown to recruit DNA repair protein RAD51 (RAD51 recombinase) to double-strand breaks and facilitate homologous recombination (HR). SQSTM1 promotes proteasomal degradation of FLNA and RAD51 within the nucleus, resulting in reduced levels of nuclear RAD51 and slower DNA repair. SQSTM1 regulates the ratio between HR and nonhomologous end joining (NHEJ) by promoting the latter at the expense of the former. This SQSTM1-dependent mechanism mediates the effect of macroautophagy on DNA repair. Moreover, nuclear localization of SQSTM1 and its association with DDF increase with aging and are prevented by life-span-extending dietary restriction, suggesting that an imbalance in the mechanism identified here may contribute to aging and age-related diseases. PMID- 27391410 TI - Change of direction ability in young elite soccer players: determining factors vary with angle variation. AB - BACKGROUND: The ability to change direction is considered of paramount importance in team sports. Currently there is a lack of consensus regarding the most important physical factors that determine change of direction (COD) ability. Therefore, the aim of this study was to examine the relationship between COD ability and targeted selected physical attributes of sprinting, isometric strength and explosive power. METHODS: Thirty-one young elite soccer players (mean+/-SD, age =17.4+/-0.6 years, height =177+/-0.5 cm; leg length =96.9+/-3.3 cm, body-mass =69.0+/-6.2 kg) were recruited. A total of eight COD tasks consisting of; a 5-m sprint then a COD of 45 degrees , 90 degrees , 135 degrees or 180 degrees followed by another 5m sprint were performed using dominant (DL) and non-dominant legs (NDL). Physical tests including a 10-m Straight-Line Sprint Test, 12 lower limb isometric strength tests, and jumping tests including: 1) five alternate Leg Jump Test; 2) triple hop distance (DL and NDL); and 3) Standing Broad Jump Test were performed. RESULTS: Stepwise multiple regression analysis showed that the physical attributes explained between 30% and 74% of the variance of the COD performance. Furthermore, these physical attributes were dependent upon COD angle and direction. CONCLUSIONS: The affecting variables of the COD performance differ according to the angle of COD and the leg used to turn. Moreover, isometric strength of the lower-limb muscles represented a major determinant factor of the COD-ability. Consequently, physical fitness coaches should include isometric muscle strengthening exercises in addition to traditional dynamic muscle strength exercises. Moreover, they should implement specific lower limb strength exercises depending on players' deficit in each COD's angles. PMID- 27391411 TI - Acute effects of scapular Kinesio Taping(r) on shoulder rotator strength, ROM and acromiohumeral distance in asymptomatic overhead athletes. AB - BACKGROUND: There is limited information in the literature that shows whether scapular taping has an effect on the acromiohumeral distance (AHD) and shoulder functions. The aim of this study was to investigate the acute effects of scapular Kinesio Taping(r) on shoulder internal rotation (IR) and external rotation (ER) strength, IR and ER range of motion (ROM) and AHD in asymptomatic overhead athletes. METHODS: Forty-one volleyball athletes (24 men, 17 women; mean age: 16.1+/-1.5 years, body mass: 66.5+/-9.6 kg, body height: 179.6+/-8.4 cm, Body Mass Index: 20.5+/-2.3 kg/m2, time participating in overhead sports activity: 6.2+/-1.4 h/week, experience in sport: 4.1+/-2.4 years) were included in this study. Shoulder IR and ER ROM, total rotation ROM, AHD, shoulder isometric IR and ER strength and ER:IR strength ratio of the dominant side were tested before and after taping. RESULTS: Scapular taping increased the shoulder IR (P<0.001) and total ROM (P<0.001), AHD (P<0.001), shoulder IR (P=0.002) and ER (P=0.006) strength. ER ROM and ER:IR ratio did not change after taping (P=0.26, P=0.98, respectively). CONCLUSIONS: The results of this study suggest that scapular taping could be an effective method for enhancing the acromiohumeral distance, shoulder rotator strength and range of motion. Therefore, scapular taping could be recommended for not only in the asymptomatic athletes' shoulder exercise training but also in the prevention of subacromial impingement syndrome. PMID- 27391412 TI - Increased cardiac output and maximal oxygen uptake in response to ten sessions of high intensity interval training. AB - BACKGROUND: Increases in maximal oxygen uptake (VO2max) are widely reported in response to completion of high intensity interval training (HIIT), yet the mechanism explaining this result is poorly understood. This study examined changes in VO2max and cardiac output (CO) in response to 10 sessions of low volume HIIT. METHODS: Participants included 30 active men and women (mean age and VO2max=22.9+/-5.4 years and 39.6+/-5.6 mL/kg/min) who performed HIIT and 30 men and women (age and VO2max=25.7+/-4.5 years and 40.7+/-5.2 mL/kg/min) who served as non-exercising controls (CON). High intensity interval training consisted of 6 10 s bouts of cycling per session at 90-110 percent peak power output (PPO) interspersed with 75 s recovery. Before and after training, progressive cycling to exhaustion was completed during which CO, stroke volume (SV), and heart rate (HR) were estimated using thoracic impedance. To confirm VO2max attainment, a verification test was completed after progressive cycling at a work rate equal to 110%PPO. RESULTS: Data demonstrated significant improvements in VO2max (2.71+/ 0.63 L/min to 2.86+/-0.63 L/min, P<0.001) and COmax (20.0+/-3.1 L/min to 21.7+/ 3.2 L/min, P=0.04) via HIIT that were not exhibited in CON. Maximal SV was increased in HIIT (P=0.04) although there was no change in maximal HR (P=0.57). CONCLUSIONS: The increase in VO2max seen in response to ten sessions of HIIT is due to improvements in oxygen delivery. PMID- 27391413 TI - Indigofera oblongifolia Prevents Lead Acetate-Induced Hepatotoxicity, Oxidative Stress, Fibrosis and Apoptosis in Rats. AB - The current study was aimed to evaluate the preventive effects of Indigofera oblongifolia leaf extract (IOLE) on lead acetate (PbAc)-induced hepatotoxicity in adult male Wistar rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days alone or in combination with the IOLE (100 mg/kg). Liver lead concentration and oxidative stress markers such as lipid peroxidation, hydrogen peroxide, nitric oxide, and glutathione content were investigated in addition to the enzymatic antioxidant activities. PbAc injection caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, hydrogen peroxide, and nitric oxide, with a concomitant decline in the glutathione content compared with the control, accompanied by a significant inhibition of antioxidant enzyme activities. The induction of oxidative stress, lead accumulation, and histological alterations in the liver were successfully minimized by pre-administration of IOLE. In addition, the PbAc group showed increase in the levels of Bax, caspase-3, and matrix metalloproteinase-9 proteins, while the expression of Bcl-2 protein was decreased. Prior administration of IOLE significantly mitigated apoptosis and fibrosis in the liver. Finally, the major components in I. oblongifolia extract were identified as polyphenols, flavonoids, and organic acids using liquid chromatography coupled mass spectroscopy. Thus, the findings of the current study revealed that I. oblongifolia had protective, anti-fibrotic, antioxidant, and anti-apoptotic activities on PbAc-induced hepatotoxicity. The beneficial effects of I. oblongifolia were in part mediated by Nrf2/HO-1 pathway. PMID- 27391416 TI - Corrigendum. PMID- 27391414 TI - Inherited heart disease - what can we expect from the second decade of human iPS cell research? AB - Induced pluripotent stem cells (iPSCs) were first generated 10 years ago. Their ability to differentiate into any somatic cell type of the body including cardiomyocytes has already made them a valuable resource for modelling cardiac disease and drug screening. Initially human iPSCs were used mostly to model known disease phenotypes; more recently, and despite a number of recognised shortcomings, they have proven valuable in providing fundamental insights into the mechanisms of inherited heart disease with unknown genetic cause using surprisingly small cohorts. In this review, we summarise the progress made with human iPSCs as cardiac disease models with special focus on the latest mechanistic insights and related challenges. Furthermore, we suggest emerging solutions that will likely move the field forward. PMID- 27391415 TI - Double jeopardy. PMID- 27391417 TI - Variation of Local Surface Properties of an Air Bubble in Water Caused by Its Interaction with Another Surface. AB - Surface and hydrodynamic forces acting between an air bubble and a flat mica surface in surfactant-free water and in 1 mM KCl solution have been investigated by observing film drainage using a modified surface force apparatus (SFA). The bubble shapes observed with the SFA are compared to theoretical profiles computed from a model that considers hydrodynamic interactions, surface curvature, and disjoining pressure arising from electrical double layer and van der Waals interactions. It is shown that the bubble experiences double-layer forces, and a final equilibrium wetting film between the bubble and mica surfaces is formed by van der Waals repulsion. However, comparison with the theoretical model reveals that the double-layer forces are not simply a function of surface separation. Rather, they appear to be changed by one of more of the following: the bubble's dynamic deformation, its proximity to another surface, and/or hydrodynamic flow in the aqueous film that separate them. The same comments apply to the hydrodynamic mobility or immobility of the air-water interface. Together the results show that the bubble's surface is "soft" in two senses: in addition to its well-known deformability, its local properties are affected by weak external forces, in this case the electrical double-layer interactions with a nearby surface and hydrodynamic flow in the neighboring aqueous phase. PMID- 27391418 TI - Evaluation of ICAM-1 and VCAM-1 Gene Polymorphisms in Patients with Periodontal Disease. AB - BACKGROUND We aimed to investigate the potential genetic relationships between the polymorphisms of gene rs5498 ICAM-1 and rs1041163 VCAM-1 and chronic periodontitis in a Chinese population within Heilongjiang. MATERIAL AND METHODS Genomic DNA was extracted from oral mucosa cells of 584 periodontal patients and 182 healthy individuals. Genotyping of the rs5498 ICAM-1 and rs1041163 VCAM-1 gene polymorphisms was performed with the Multiplex SNaPshot technique. RESULTS Statistically significant associations were identified between the chronic periodontal patients and the controls in the gene polymorphisms of rs5498 ICAM-1 (P=0.007) and rs1041163 VCAM-1 (P=0.029). The distribution of rs5498 (P=0.029) and rs1041163 (P=0.049) differed significantly across the mild, moderate, and severe groups of periodontitis. CONCLUSIONS Our findings indicate that ICAM-1 rs5498 and VCAM-1 rs1041163 polymorphisms contribute to chronic periodontitis, and ICAM-1 rs5498 and VCAM-1 rs1041163 gene polymorphisms might be associated with periodontitis severity in the Heilongjiang Chinese population. Further studies should be conducted to determine whether these polymorphisms could be used as biomarkers of periodontitis. PMID- 27391419 TI - Transition-metal-free oxychlorination of alkenyl oximes: in situ generated radicals with tert-butyl nitrite. AB - Oxychlorination of alkenyl oximes is harder compared to the analogous oxybromination or oxyiodination because of the difficulty associated with the formation of chlorine cations or radicals. A transition-metal-free oxychlorination of alkenyl oximes has been developed, using t-BuONO as a dual oxidant and AlCl3 as a chlorine source. This convenient and practical method has been used to construct chloroisoxazolines in moderate to good yields, whereas N chlorosuccinimide (NCS) failed to promote this reaction. PMID- 27391420 TI - The Evolution of Diapsid Reproductive Strategy with Inferences about Extinct Taxa. AB - Diapsids show an extremely wide range of reproductive strategies. Offspring may receive no parental care, care from only one sex, care from both parents, or care under more complex regimes. Young may vary from independent, super-precocial hatchlings to altricial neonates needing much care before leaving the nest. Parents can invest heavily in a few young, or less so in a larger number. Here we examine the evolution of these traits across a composite phylogeny spanning the extant diapsids and including the limited number of extinct taxa for which reproductive strategies can be well constrained. Generalized estimating equation(GEE)-based phylogenetic comparative methods demonstrate the influences of body mass, parental care strategy and hatchling maturity on clutch volume across the diapsids. The influence of polygamous reproduction is not important despite a large sample size. Applying the results of these models to the dinosaurs supports the hypothesis of paternal care (male only) in derived non avian theropods, previously suggested based on simpler analyses. These data also suggest that sauropodomorphs did not care for their young. The evolution of parental-care occurs in an almost linear series of transitions. Paternal care rarely gives rise to other care strategies. Where hatchling condition changes, diapsids show an almost unidirectional tendency of evolution towards increased altriciality. Transitions to social monogamy from the ancestral state in diapsids, where both sexes are polygamous, are common. In contrast, once evolved, polygyny and polyandry are very evolutionarily stable. Polygyny and maternal care correlate, as do polyandry and paternal care. Ancestral-character estimation (ACE) of these care strategies with the character transition likelihoods estimated from the original data gives good confidence at most important nodes. These analyses suggest that the basalmost diapsids had no parental care. Crocodilians independently evolved maternal care, paternal care evolved in the saurischian line, prior to derived theropod dinosaurs, and the most basal neognaths likely exhibited biparental care. Overall, the evolution of parental care among diapsids shows a persistent trend towards increased care of offspring, and more complex care strategies and behaviors with time. Reversions to reduced care are infrequent. PMID- 27391421 TI - Occurrence of Mutations in the Antimicrobial Target Genes Related to Levofloxacin, Clarithromycin, and Amoxicillin Resistance in Helicobacter pylori Isolates from Buenos Aires City. AB - Domain V of 23S rRNA, gyrA and gyrB Quinolones Resistance-Determining Region (QRDR), and pbp-1A gene point mutations were investigated in Helicobacter pylori resistant isolates from three centres of Buenos Aires. Minimal inhibitory concentrations (MICs) were performed in 197 isolates from 52 H. pylori-positive naive patients by agar dilution method. Point mutations were achieved by amplification and sequencing of the target genes, and their association with resistance was determined by natural transformation assays. Resistance rates were as follows: metronidazole 28.8%, clarithromycin (CLA) 26.9%, levofloxacin (LEV) 32.7%, and amoxicillin (AMX) 7.6%. Nearly one-third of patients carried multidrug resistant isolates. A2143G or A2142G in domain V of 23S-rRNA was found in all isolates showing high level of resistance to CLA (MIC >2 mg/L), accounting for 76.0% (38/50) of those with the resistant phenotype. The mutations A2267G or T1861C carried by 8/12 isolates with MIC 1-2 mg/L (low level) did not confer resistance by transformation. Substitutions at GyrA position 87 or 91, mainly N87K and D91G, were found in 92.8% (52/56) of the LEV-resistant isolates: 48 isolates with MIC 4-64 mg/L and 4/8 isolates with MIC 2 mg/L. The remaining four harboured K133N, also present in susceptible isolates. None of the substitutions in GyrB demonstrated to confer resistance. Transformation proved that PBP-1A N562Y and/or T556S substitutions confer the AMX resistance in our isolates, showing an additive effect. In conclusion, the usually reported mutations related to CLA, LEV, and AMX resistance were found in our isolates. However, low-level CLA resistance seems not to be due to mutations in Domain V of 23S rRNA gene. PMID- 27391422 TI - Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/beta-catenin signalling in NSCLC. AB - Cancer stem cells (CSCs) are commonly associated with cancer recurrence and metastasis that occurs in up to 30-55% of non-small-cell lung carcinoma (NSCLC) patients. Herein, we showed that serine-arginine protein kinase 1 (SRPK1) was highly expressed at both the mRNA and the protein levels in human NCSLC. SRPK1 was associated with the clinical features of human NSCLC, including clinical stage (p < 0.001) and T (p = 0.001), N (p = 0.007), and M (p = 0.001) classifications. Ectopic overexpression of SRPK1 promoted the acquisition of a stem cell-like phenotype in human NSCLC cell lines cultured in vitro. Overexpression of SRPK1 increased sphere formation and the proportion of side population cells that exclude Hoechst dye. Conversely, SRPK1 silencing reduced the number of spheres and the proportion of side-population cells. Mouse studies indicated that SRPK1 promoted NSCLC cell line tumour growth and SRPK1 overexpression reduced the number of tumour cells required to initiate tumourigenesis in vivo. Mechanistically, gene set enrichment analysis showed that Wnt/beta-catenin signalling correlated with SRPK1 mRNA levels and this signalling pathway was hyperactivated by ectopic SRPK1 expression in NSCLC cell lines. Immunofluorescence demonstrated that SRPK1 enhanced beta-catenin accumulation in the nuclei of NSCLC cell lines, and inhibition of beta-catenin signalling abrogated the SRPK1-induced stem cell-like phenotype. Together, our findings suggest that SRPK1 promotes a stem cell-like phenotype in NSCLC via Wnt/beta catenin signalling. Moreover, SRPK1 may represent a novel target for human NSCLC diagnosis and therapy. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27391423 TI - Parathyroid Hormone-Related Peptide (1-36) Enhances Beta Cell Regeneration and Increases Beta Cell Mass in a Mouse Model of Partial Pancreatectomy. AB - AIMS/HYPOTHESIS: Finding ways to stimulate the regeneration of endogenous pancreatic beta cells is an important goal in the treatment of diabetes. Parathyroid hormone-related protein (PTHrP), the full-length (1-139) and amino terminal (1-36) peptides, enhance beta cell function, proliferation, and survival. Therefore, we hypothesize that PTHrP(1-36) has the potential to regenerate endogenous beta cells. METHODS: The partial pancreatectomy (PPx) mouse model of beta cell injury was used to test this hypothesis. Male Balb/c mice underwent either sham-operation or PPx, and were subsequently injected with PTHrP(1-36) (160MUg/kg) or vehicle (veh), for 7, 30, or 90 days. The four groups of mice, sham-veh, sham-PTHrP, PPx-veh, and PPx-PTHrP were assessed for PTHrP and receptor expression, and glucose and beta cell homeostasis. RESULTS: PTHrP receptor, but not the ligand, was significantly up-regulated in islets from mice that underwent PPx compared to sham-operated mice. This suggests that exogenous PTHrP could further enhance beta cell regeneration after PPx. PTHrP did not significantly affect body weight, blood glucose, plasma insulin, or insulin sensitivity, in either sham or PPx mice. Glucose tolerance improved in the PPx PTHrP versus PPx-veh mice only in the early stages of treatment. As hypothesized, there was a significant increase in beta cell proliferation in PPx-PTHrP mice at days 7 and 30; however, this was normalized by day 90, compared to PPx-veh mice. Enhanced beta cell proliferation translated to a marked increase in beta cell mass at day 90, in PPx-PTHrP versus PPx-veh mice. CONCLUSIONS: PTHrP(1-36) significantly enhances beta cell regeneration through increased beta cell proliferation and beta cell mass after PPx. Future studies will determine the potential of PTHrP to enhance functional beta cell mass in the setting of diabetes. PMID- 27391424 TI - Foliar Nutrient Distribution Patterns in Sympatric Maple Species Reflect Contrasting Sensitivity to Excess Manganese. AB - Sugar maple and red maple are closely-related co-occurring tree species significant to the North American forest biome. Plant abiotic stress effects including nutritional imbalance and manganese (Mn) toxicity are well documented within this system, and are implicated in enhanced susceptibility to biotic stresses such as insect attack. Both tree species are known to overaccumulate foliar manganese (Mn) when growing on unbuffered acidified soils, however, sugar maple is Mn-sensitive, while red maple is not. Currently there is no knowledge about the cellular sequestration of Mn and other nutrients in these two species. Here, electron-probe x-ray microanalysis was employed to examine cellular and sub cellular deposition of excessively accumulated foliar Mn and other mineral nutrients in vivo. For both species, excess foliar Mn was deposited in symplastic cellular compartments. There were striking between-species differences in Mn, magnesium (Mg), sulphur (S) and calcium (Ca) distribution patterns. Unusually, Mn was highly co-localised with Mg in mesophyll cells of red maple only. The known sensitivity of sugar maple to excess Mn is likely linked to Mg deficiency in the leaf mesophyll. There was strong evidence that Mn toxicity in sugar maple is primarily a symplastic process. For each species, leaf-surface damage due to biotic stress including insect herbivory was compared between sites with acidified and non-acidified soils. Although it was greatest overall in red maple, there was no difference in biotic stress damage to red maple leaves between acidified and non-acidified soils. Sugar maple trees on buffered non-acidified soil were less damaged by biotic stress compared to those on unbuffered acidified soil, where they are also affected by Mn toxicity abiotic stress. This study concluded that foliar nutrient distribution in symplastic compartments is a determinant of Mn sensitivity, and that Mn stress hinders plant resistance to biotic stress. PMID- 27391426 TI - Habituation of self-motion perception following unidirectional angular velocity steps. AB - We investigated whether the perceived angular velocity following velocity steps of 80 degrees /s in the dark decreased with the repetition of the stimulation in the same direction. The perceptual response to velocity steps in the opposite direction was also compared before and after this unidirectional habituation training. Participants indicated their perceived angular velocity by clicking on a wireless mouse every time they felt that they had rotated by 90 degrees . The prehabituation perceptual response decayed exponentially with a time constant of 23.9 s. After 100 velocity steps in the same direction, this time constant was 12.9 s. The time constant after velocity steps in the opposite direction was 13.4 s, indicating that the habituation of the sensation of rotation is not direction specific. The peak velocity of the perceptual response was not affected by the habituation training. The differences between the habituation characteristics of self-motion perception and eye movements confirm that different velocity storage mechanisms mediate ocular and perceptual responses. PMID- 27391427 TI - Inhibition of sphingomyelin synthase 1 affects ceramide accumulation and hydrogen peroxide-induced apoptosis in Neuro-2a cells. AB - Oxidative stress plays a key role in brain injury after cerebral ischemia reperfusion, which contributes toward excessive apoptosis of nerve cells. Therefore, it would be beneficial to identify a therapy that could interfere with the progression of apoptosis and protect the brain from ischemia-reperfusion injury. As ceramide, a well-known second messenger of apoptosis, can be metabolized by sphingomyelin synthase 1 (SMS1), recent research has focused on the link between SMS1 and apoptosis in different cells. To investigate whether SMS1 is involved in the process of oxidative stress-induced apoptosis in neurons and to explore the possible underlying mechanism, we treated mouse neuroblastoma Neuro-2A (N2a) cells with hydrogen peroxide (H2O2). Incubation with H2O2 significantly upregulated the expression of SMS1, increased the intracellular levels of ceramide and sphingomyelin synthase activity, and induced apoptosis. Moreover, pretreatment of N2a cells with D609, an sphingomyelin synthase inhibitor, or SMS1-silencing RNA (siRNA) further increased ceramide and potentiated H2O2-induced apoptosis which could be reversed by SB203580 (a p38 inhibitor). Thus, our study has shown that SMS1 regulates ceramide levels in N2a cells and plays a potent protective role in this oxidative stress-induced apoptosis partly through the p38 pathway. PMID- 27391428 TI - Immobilization stress-induced anorexia is mediated independent of MyD88. AB - MyD88 is an adaptor protein for the toll-like receptor, which is involved in regulating innate immune function. Lipopolysaccharide-induced activation of toll like receptor 4 signaling induces hypothalamic signal transducer and activator of transcription 3 (STAT3) phosphorylation and anorexia through MyD88. In the present study, we investigated the possible role of MyD88 in psychological stress induced anorexia. We found that immobilization stress inhibited food intake in both wild-type mice and MyD88-deficient mice. Immobilization stress slightly increased STAT3 phosphorylation in the hypothalamus, but it was weaker than the lipopolysaccharide-induced increase in STAT3 phosphorylation. These observations suggest that the mechanisms involved in psychological stress-induced anorexia may be regulated differently from those involved in anorexia that is induced by infection. PMID- 27391425 TI - Molecular, Biochemical, and Dietary Regulation Features of alpha-Amylase in a Carnivorous Crustacean, the Spiny Lobster Panulirus argus. AB - Alpha-amylases are ubiquitously distributed throughout microbials, plants and animals. It is widely accepted that omnivorous crustaceans have higher alpha amylase activity and number of isoforms than carnivorous, but contradictory results have been obtained in some species, and carnivorous crustaceans have been less studied. In addition, the physiological meaning of alpha-amylase polymorphism in crustaceans is not well understood. In this work we studied alpha amylase in a carnivorous lobster at the gene, transcript, and protein levels. It was showed that alpha-amylase isoenzyme composition (i.e., phenotype) in lobster determines carbohydrate digestion efficiency. Most frequent alpha-amylase phenotype has the lowest digestion efficiency, suggesting this is a favoured trait. We revealed that gene and intron loss have occurred in lobster alpha amylase, thus lobsters express a single 1830 bp cDNA encoding a highly conserved protein with 513 amino acids. This protein gives rise to two isoenzymes in some individuals by glycosylation but not by limited proteolysis. Only the glycosylated isoenzyme could be purified by chromatography, with biochemical features similar to other animal amylases. High carbohydrate content in diet down regulates alpha-amylase gene expression in lobster. However, high alpha-amylase activity occurs in lobster gastric juice irrespective of diet and was proposed to function as an early sensor of the carbohydrate content of diet to regulate further gene expression. We concluded that gene/isoenzyme simplicity, post translational modifications and low Km, coupled with a tight regulation of gene expression, have arose during evolution of alpha-amylase in the carnivorous lobster to control excessive carbohydrate digestion in the presence of an active alpha-amylase. PMID- 27391429 TI - Arenaviral vaccine vectors to combat infectious diseases. PMID- 27391430 TI - DeltaNp63 mediates cellular survival and metastasis in canine osteosarcoma. AB - p63 is a structural homolog within the 53 family encoding two isoforms, DeltaNp63 and TAp63. The oncogenic activity of DeltaNp63 has been demonstrated in multiple cancers, however the underlying mechanisms that contribute to tumorigenesis are poorly characterized. Osteosarcoma (OSA) is the most common primary bone tumor in dogs, exhibiting clinical behavior and molecular biology essentially identical to its human counterpart. The purpose of this study was to evaluate the potential contribution of DeltaNp63 to the biology of canine OSA. As demonstrated by qRT PCR, nearly all canine OSA cell lines and tissues overexpressed DeltaNp63 relative to normal control osteoblasts. Inhibition of DeltaNp63 by RNAi selectively induced apoptosis in the OSA cell lines overexpressing DeltaNp63. Knockdown of DeltaNp63 upregulated expression of the proapoptotic Bcl-2 family members Puma and Noxa independent of p53. However the effects of DeltaNp63 required transactivating isoforms of p73, suggesting that DeltaNp63 promotes survival in OSA by repressing p73-dependent apoptosis. In addition, DeltaNp63 modulated angiogenesis and invasion through its effects on VEGF-A and IL-8 expression, and STAT3 phosphorylation. Lastly, the capacity of canine OSA cell lines to form pulmonary metastasis was directly related to expression levels of DeltaNp63 in a murine model of metastatic OSA. Together, these data demonstrate that DeltaNp63 inhibits apoptosis and promotes metastasis, supporting continued evaluation of this oncogene as a therapeutic target in both human and canine OSA. PMID- 27391431 TI - HMGB1 overexpression as a prognostic factor for survival in cancer: a meta analysis and systematic review. AB - As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer. PMID- 27391432 TI - Long non-coding RNAs: novel prognostic biomarkers for liver metastases in patients with early stage colorectal cancer. AB - Liver metastasis is the primary cause of death for colorectal cancer (CRC) patients. To investigate the prognostic value of long non-coding RNAs (lncRNAs) on colorectal liver metastases, quantitative reverse-transcriptase PCR (quantitative RT-PCR) was performed on 15 lncRNAs in 51 stage IV CRC with liver metastases and 57 stage I/II CRC specimens. The expression levels of four lncRNAs (GAS5, H19, MEG3 and Yiya) were significantly different between liver metastases and primary tumors of stage IV CRC patients. Furthermore, the high expression levels of GAS5 and Yiya were significantly associated with future occurrence of liver metastases in early stage CRC patients. Kaplan-Meier analysis showed that the high expression levels of GAS5 or Yiya were correlated with poor prognosis of early stage CRC patients (p = 0.0206 and 0.0005 for GAS5 and Yiya, respectively). Yiya expression was proved to be an independent prognostic indicator of colorectal liver metastases in a multivariate analysis (relative risk = 10.7; p < 0.0001). Our study revealed that GAS5 and Yiya were promising prognostic biomarkers of liver metastases for early stage CRC patients. PMID- 27391433 TI - Dasatinib modulates sensitivity to pemetrexed in malignant pleural mesothelioma cell lines. AB - BACKGROUND: Thymidylate synthase (TS), one of the key enzymes for thymidine synthesis, is a target of pemetrexed (PEM), a key agent for the systemic therapy of malignant pleural mesothelioma (MPM) and its overexpression has been correlated to PEM-resistance. In MPM, experimental data report activation of the c-SRC tyrosine kinase suggesting it as a potential target to be further investigated. RESULTS: MPM cell lines showed different sensitivity, being MSTO the most and REN the least sensitive to PEM. REN cells showed high levels of both TS and SRC: dasatinib inhibited SRC activation and suppressed TS protein expression, starting from 100 nM dose, blocking the PEM-induced up regulation of TS protein levels. Dasatinib treatment impaired cells migration, and both sequential and co-administration with PEM significantly increased apoptosis. Dasatinib pretreatment improved sensitivity to PEM, downregulated TS promoter activity and, in association with PEM, modulated the downstream PI3K-Akt-mTOR signaling. Cell lines and Methods: In three MPM cell lines (MPP89, REN and MSTO), the effects of c-SRC inhibition, in correlation with TS expression and PEM sensitivity, were evaluated. PEM and dasatinib, a SRC inhibitor, were administered as single agents, in combination or sequentially. Cell viability, apoptosis and migration, as well as TS expression and SRC activation have been assessed. CONCLUSIONS: These data indicate that dasatinib sensitizes mesothelioma cells to PEM through TS down-regulation. PMID- 27391434 TI - A key role for transketolase-like 1 in tumor metabolic reprogramming. AB - Metabolic reprogramming, a crucial cancer hallmark, shifts metabolic pathways such as glycolysis, tricarboxylic acid cycle or lipogenesis, to enable the growth characteristics of cancer cells. Here, we provide evidence that transketolase like 1 (TKTL1) orchestrates aerobic glycolysis, fatty acid and nucleic acid synthesis, glutamine metabolism, protection against oxidative stress and cell proliferation. Furthermore, silencing of TKTL1 reduced the levels of sphingolipids such as lactosylceramide (a sphingolipid regulating cell survival, proliferation and angiogenesis) and phosphatidylinositol (which activates PI3K/Akt/mTOR signaling). Thus, in addition to its well-known roles in glucose and amino acid metabolism, TKTL1 also regulates lipid metabolism. In conclusion, our study provides unprecedented evidence that TKTL1 plays central roles in major metabolic processes subject to reprogramming in cancer cells and thus identifies TKTL1 as a promising target for new anti-cancer therapies. PMID- 27391435 TI - Parp1 protects against Aag-dependent alkylation-induced nephrotoxicity in a sex dependent manner. AB - Nephrotoxicity is a common toxic side-effect of chemotherapeutic alkylating agents. Although the base excision repair (BER) pathway is essential in repairing DNA alkylation damage, under certain conditions the initiation of BER produces toxic repair intermediates that damage healthy tissues. We have shown that the alkyladenine DNA glycosylase, Aag (a.k.a. Mpg), an enzyme that initiates BER, mediates alkylation-induced whole-animal lethality and cytotoxicity in the pancreas, spleen, retina, and cerebellum, but not in the kidney. Cytotoxicity in both wild-type and Aag-transgenic mice (AagTg) was abrogated in the absence of Poly(ADP-ribose) polymerase-1 (Parp1). Here we report that Parp1-deficient mice expressing increased Aag (AagTg/Parp1-/-) develop sex-dependent kidney failure upon exposure to the alkylating agent, methyl methanesulfonate (MMS), and suffer increased whole-animal lethality compared to AagTg and wild-type mice. Macroscopic, histological, electron microscopic and immunohistochemical analyses revealed morphological kidney damage including dilated tubules, proteinaceous casts, vacuolation, collapse of the glomerular tuft, and deterioration of podocyte structure. Moreover, mice exhibited clinical signs of kidney disease indicating functional damage, including elevated blood nitrogen urea and creatinine, hypoproteinemia and proteinuria. Pharmacological Parp inhibition in AagTg mice also resulted in sensitivity to MMS-induced nephrotoxicity. These findings provide in vivo evidence that Parp1 modulates Aag-dependent MMS-induced nephrotoxicity in a sex-dependent manner and highlight the critical roles that Aag-initiated BER and Parp1 may play in determining the side-effects of chemotherapeutic alkylating agents. PMID- 27391436 TI - Noninvasive ventilation improves cardiac function in patients with chronic heart failure. AB - Chronic heart failure (CHF) has been shown to be associated with an increased incidence of sleep-disordered breathing. Whether treatment with noninvasivepositive-pressure ventilation (NPPV), including continuous positive airway pressure, bi-level positive airway pressure and adaptive servo ventilation, improves clinical outcomes of CHF patients is still debated. 2,832 CHF patients were enrolled in our analysis. NPPV was significantly associated with improvement in left ventricular ejection fraction (39.39% vs. 34.24%; WMD, 5.06; 95% CI, 3.30-6.81; P < 0.00001) and plasma brain natriuretic peptide level (268.23 pg/ml vs. 455.55 pg/ml; WMD, -105.66; 95% CI, [-169.19]-[-42.13]; P = 0.001). However, NPPV did not reduce all-cause mortality (0.26% vs. 0.24%; OR, 1.13; 95% CI, 0.93-1.37; P = 0.22) or re-hospitalization rate (57.86% vs. 59.38%; OR, 0.47; 95% CI, 0.19-1.19; P = 0.02) as compared with conventional therapy. Despite no benefits on hard endpoints, NPPV may improve cardiac function of CHF patients. These data highlight the important role of NPPV in the therapy of CHF. PMID- 27391437 TI - Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study. AB - BACKGROUND: The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. RESULTS: 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. METHODS: Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (um) and group B with RTA equal to or more than 250 um. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). CONCLUSIONS: The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID- 27391438 TI - Prognostic significance of survivin in rectal cancer patients treated with surgery and postoperative concurrent chemo-radiation therapy. AB - BACKGROUND & AIMS: This study is designed to investigate the expression of survivin and p53 in human rectal cancer tissues and analyze associations between expression and clinical outcomes in terms of disease recurrence and survival duration. RESULTS: During follow-up (median 119.0, range 6.6 to 161.3 months), tumor recurrence was detected in 50 patients (43.1%), and local recurrence developed as a first failure site in 13 patients (11.2%). Positive immunostaining of nuclear and cytoplasmic survivin was observed in about one quarter of patients, and about half of all patients had positive staining for p53. Both survivin and p53 were significant prognostic factors of disease-free survival in the univariate analyses, but only survivin remained a significant prognostic factor in the multivariate analysis. METHODS: We performed a retrospective study with 116 locally advanced rectal cancer patients who underwent total mesorectal excision (TME) followed by postoperative concurrent chemo-radiation therapy (CCRT). Immunohistochemical staining was conducted using antibodies for survivin or p53, and their expression was analyzed using an individual score that combined the percentage of positive cells and staining intensity. CONCLUSIONS: Overexpression of nuclear and cytoplasmic survivin in locally advanced rectal cancer patients was associated with a higher recurrence rate in rectal cancer patients treated with TME followed by postoperative CCRT. PMID- 27391439 TI - Activation of oncogenic tyrosine kinase signaling promotes insulin receptor mediated cone photoreceptor survival. AB - In humans, daylight vision is primarily mediated by cone photoreceptors. These cells die in age-related retinal degenerations. Prolonging the life of cones for even one decade would have an enormous beneficial effect on usable vision in an aging population. Photoreceptors are postmitotic, but shed 10% of their outer segments daily, and must synthesize the membrane and protein equivalent of a proliferating cell each day. Although activation of oncogenic tyrosine kinase and inhibition of tyrosine phosphatase signaling is known to be essential for tumor progression, the cellular regulation of this signaling in postmitotic photoreceptor cells has not been studied. In the present study, we report that a novel G-protein coupled receptor-mediated insulin receptor (IR) signaling pathway is regulated by non-receptor tyrosine kinase Src through the inhibition of protein tyrosine phosphatase IB (PTP1B). We demonstrated the functional significance of this pathway through conditional deletion of IR and PTP1B in cones, in addition to delaying the death of cones in a mouse model of cone degeneration by activating the Src. This is the first study demonstrating the molecular mechanism of a novel signaling pathway in photoreceptor cells, which provides a window of opportunity to save the dying cones in retinal degenerative diseases. PMID- 27391440 TI - Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy. AB - Protein misfolded oligomers are considered the most toxic species amongst those formed in the process of amyloid formation and the molecular basis of their toxicity, although not completely understood, is thought to originate from the interaction with the cellular membrane. Here, we sought to highlight the molecular determinants of oligomer-membrane interaction by atomic force microscopy. We monitored the interaction between multiphase supported lipid bilayers and two types of HypF-N oligomers displaying different structural features and cytotoxicities. By our approach we imaged with unprecedented resolution the ordered and disordered lipid phases of the bilayer and different oligomer structures interacting with either phase. We identified the oligomers and lipids responsible for toxicity and, more generally, we established the importance of the membrane lipid component in mediating oligomer toxicity. Our findings support the importance of GM1 ganglioside in mediating the oligomer bilayer interaction and support a mechanism of oligomer cytotoxicity involving bilayer destabilization by globular oligomers within GM1-rich ordered raft regions rather than by annular oligomers in the surrounding disordered membrane domains. PMID- 27391441 TI - Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non canonical ATM/ATR signaling. AB - RNA polymerase I (Pol I)-mediated transcription of the ribosomal RNA genes (rDNA) is confined to the nucleolus and is a rate-limiting step for cell growth and proliferation. Inhibition of Pol I by CX-5461 can selectively induce p53-mediated apoptosis of tumour cells in vivo. Currently, CX-5461 is in clinical trial for patients with advanced haematological malignancies (Peter Mac, Melbourne). Here we demonstrate that CX-5461 also induces p53-independent cell cycle checkpoints mediated by ATM/ATR signaling in the absence of DNA damage. Further, our data demonstrate that the combination of drugs targeting ATM/ATR signaling and CX-5461 leads to enhanced therapeutic benefit in treating p53-null tumours in vivo, which are normally refractory to each drug alone. Mechanistically, we show that CX-5461 induces an unusual chromatin structure in which transcriptionally competent relaxed rDNA repeats are devoid of transcribing Pol I leading to activation of ATM signaling within the nucleoli. Thus, we propose that acute inhibition of Pol transcription initiation by CX-5461 induces a novel nucleolar stress response that can be targeted to improve therapeutic efficacy. PMID- 27391442 TI - A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma. AB - PURPOSE: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality. The objective of this study was to primarily assess the safety of intratumoral ipilimumab/IL-2 combination and to obtain data on clinical efficacy. RESULTS: There was no dose limiting toxicity. While local response of injected lesions was observed in 67% patients (95% CI, 40%-93%), an abscopal response was seen in 89% (95% CI, 68%-100%). The overall response rate and clinical benefit rate by immune related response criteria (irRC) was 40% (95% CI, 10%-70%) and 50% (95% CI, 19% 81%), respectively. Enhanced systemic immune response was observed in most patients and correlated with clinical responses. EXPERIMENTAL DESIGN: Twelve patients with unresectable stages III/IV melanoma were enrolled. A standard 3+3 design was employed to assess highest tolerable intratumoral dose of ipilimumab and IL-2 based on toxicity during the first three weeks. Escalated doses of ipilimumab was injected into only one lesion weekly for eight weeks in cohorts of three patients. A fixed dose of IL-2 was injected three times a week into the same lesion for two weeks, followed by two times a week for six weeks. CONCLUSIONS: Intratumoral injection with the combination of ipilimumab/IL-2 is well tolerated and generates responses in both injected and non-injected lesions in the majority of patients. PMID- 27391443 TI - Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes. AB - Connexin43 (Cx43), the major protein forming gap junctions in astrocytes, is reduced in high-grade gliomas, where its ectopic expression exerts important effects, including the inhibition of the proto-oncogene tyrosine-protein kinase Src (c-Src). In this work we aimed to investigate the mechanism responsible for this effect. The inhibition of c-Src requires phosphorylation at tyrosine 527 mediated by C-terminal Src kinase (Csk) and dephosphorylation at tyrosine 416 mediated by phosphatases, such as phosphatase and tensin homolog (PTEN). Our results showed that the antiproliferative effect of Cx43 is reduced when Csk and PTEN are silenced in glioma cells, suggesting the involvement of both enzymes. Confocal microscopy and immunoprecipitation assays confirmed that Cx43, in addition to c-Src, binds to PTEN and Csk in glioma cells transfected with Cx43 and in astrocytes. Pull-down assays showed that region 266-283 in Cx43 is sufficient to recruit c-Src, PTEN and Csk and to inhibit the oncogenic activity of c-Src. As a result of c-Src inhibition, PTEN was increased with subsequent inactivation of Akt and reduction of proliferation of human glioblastoma stem cells. We conclude that the recruitment of Csk and PTEN to the region between residues 266 and 283 within the C-terminus of Cx43 leads to c-Src inhibition. PMID- 27391444 TI - Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway. AB - Effector T cell migration through the tissue extracellular matrix (ECM) is an important step of the adaptive immune response and in the development of inflammatory diseases. However, the mechanisms involved in this process are still poorly understood. In this study, we addressed the role of a collagen receptor, the discoidin domain receptor 1 (DDR1), in the migration of Th17 cells. We showed that the vast majority of human Th17 cells express DDR1 and that silencing DDR1 or using the blocking recombinant receptor DDR1:Fc significantly reduced their motility and invasion in three-dimensional (3D) collagen. DDR1 promoted Th17 migration by activating RhoA/ROCK and MAPK/ERK signaling pathways. Interestingly, the RhoA/ROCK signaling module was required for MAPK/ERK activation. Finally, we showed that DDR1 is important for the recruitment of Th17 cells into the mouse dorsal air pouch containing the chemoattractant CCL20. Collectively, our results indicate that DDR1, via the activation of RhoA/ROCK/MAPK/ERK signaling axis, is a key pathway of effector T cell migration through collagen of perivascular tissues. As such, DDR1 can contribute to the development of Th17-dependent inflammatory diseases. PMID- 27391445 TI - Surgical Outcomes of Inferior Oblique Myectomy in Unilateral Congenital Superior Oblique Palsy with or without Trochlear Nerve. AB - OBJECTIVES: To compare the surgical outcomes of inferior oblique (IO) myectomy in congenital superior oblique palsy (SOP) according to the presence of the trochlear nerve identified with high-resolution MRI. DATA EXTRACTION: Forty-one congenital SOP patients without a trochlear nerve (absent group) and 23 patients with a trochlear nerve (present group) who underwent IO myectomy as the primary surgical treatment were retrospectively reviewed. "Motor success" was defined as postoperative ipsilateral hypertropia <= 4 prism diopter (PD). "Head tilt improvement" was regarded as postoperative angle of head tilt < 5 degrees ( degrees ). Success rates for motor alignment and head tilt improvement, cumulative probabilities of success, and factors influencing surgical responses were evaluated. RESULTS: The cumulative probabilities of motor success at 2 years after IO myectomy were 92% in patients with a trochlear nerve and 86% in patients without a trochlear nerve (P = 0.138). The cumulative probabilities of undercorrection and recurrence of hypertropia after 2 years were 0% in the present group versus 21% in the absent group (P = 0.014). The cumulative probabilities of persistent head tilt after 2 years were 14% in the present group and 20% in the absent group (P = 0.486). A younger age at operation was associated with reduced probabilities of motor success and head tilt improvement (P = 0.009, P = 0.022 respectively). A greater preoperative angle of head tilt was associated with persistent head tilt after surgery (P = 0.038). CONCLUSIONS: Congenital SOP without a trochlear nerve had a higher risk of hypertropia undercorrection after IO myectomy compared to patients with a trochlear nerve. A younger age at operation and larger preoperative head tilt was related to poor outcomes. PMID- 27391446 TI - Severe Psychological Distress of Evacuees in Evacuation Zone Caused by the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey. AB - BACKGROUND: Following the Great East Japan Earthquake on March 11, 2011, the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant has continued to affect the mental health status of residents in the evacuation zone. To examine the mental health status of evacuee after the nuclear accident, we conducted the Mental Health and Lifestyle Survey as part of the ongoing Fukushima Health Management Survey. METHODS: We measured mental health status using the Kessler 6 item psychological distress scale (K6) in a total of 73,569 (response rate: 40.7%) evacuees aged 15 and over who lived in the evacuation zone in Fukushima Prefecture. We then dichotomized responders using a 12/13 cutoff on the K6, and compared the proportion of K6 scores >=13 and <=12 in each risk factor including demographic information, socioeconomic variables, and disaster-related variables. We also performed bivariate analyses between mental health status and possible risk factors using the chi-square test. Furthermore, we performed multivariate regression analysis using modified Poisson regression models. RESULTS: The median K6 score was 5 (interquartile range: 1-10). The number of psychological distress was 8,717 (14.6%). We found that significant differences in the prevalence of psychological distress by almost all survey items, including disaster-related risk factors, most of which were also associated with increased Prevalence ratios (PRs). Additionally, we found that psychological distress in each evacuation zone was significantly positively associated with the radiation levels in their environment (r = 0.768, p = 0.002). CONCLUSION: The earthquake, tsunami and subsequent nuclear accident likely caused severe psychological distress among residents in the evacuation zone in Fukushima Prefecture. The close association between psychological distress and the radiation levels shows that the nuclear accident seriously influenced the mental health of the residents, which might be exacerbated by increased risk perception. To provide prompt and appropriate support, continued psychosocial intervention for evacuees is strongly recommended. PMID- 27391447 TI - Intraspecific Polymorphisms of Cytogenetic Markers Mapped on Chromosomes of Triticum polonicum L. AB - Triticum genus encloses several tetraploid species that are used as genetic stocks for expanding the genetic variability of wheat (Triticum aestivum L.). Although the T. aestivum (2n = 6x = 42, AABBDD) and T. durum (2n = 4x = 28, AABB) karyotypes were well examined by chromosome staining, Giemsa C-banding and FISH markers, other tetraploids are still poorly characterized. Here, we established and compared the fluorescence in situ hybridization (FISH) patterns on chromosomes of 20 accessions of T. polonicum species using different repetitive sequences from BAC library of wheat 'Chinese Spring'. The chromosome patterns of Polish wheat were compared to tetraploid (2n = 4x = 28, AABB) Triticum species: T. durum, T. diccocon and T. turanicum, as well. A combination of pTa-86, pTa-535 and pTa-713 probes was the most informative among 6 DNA probes tested. Probe pTa k374, which is similar to 28S rDNA sequence enabled to distinguish signal size and location differences, as well as rDNA loci elimination. Furthermore, pTa-465 and pTa-k566 probes are helpful for the detection of similar organized chromosomes. The polymorphisms of signals distribution were observed in 2A, 2B, 3B, 5B, 6A and 7B chromosomes. Telomeric region of the short arm of 6B chromosome was the most polymorphic. Our work is novel and contributes to the understanding of T. polonicum genome organization which is essential to develop successful advanced breeding strategies for wheat. Collection and characterization of this germplasm can contribute to the wheat biodiversity safeguard. PMID- 27391449 TI - Sleep difficulties and their impact on recovery following mild traumatic brain injury in children. AB - OBJECTIVE: To determine the frequency of sleep difficulties in children following mild traumatic brain injury (TBI) over time and explore the role of sleep on recovery and behaviour. METHODS: Longitudinal study of 109 children aged between 8-16 years who had experienced a mild TBI, with an embedded case control study. Parents completed assessments of the child's sleep quality, symptoms and behaviour at baseline, 1, 6 and 12 months post-injury. Regression analyses explored the impact of poor sleep on 12-month outcomes. Healthy control children were assessed at one time point for comparison to determine the longer-term impact of brain injury on sleep. RESULTS: The number of children experiencing poor sleep quality peaked 1-month post-injury (39%), reducing to 28% 12-months post-injury. Poor sleep quality at 1-month was associated with increased frequency and severity of symptoms and poorer behavioural outcomes 1 year post TBI. Cases with TBI were significantly more likely to have sleep difficulties 1 year post-injury than controls (Odds ratio = 3.09). CONCLUSIONS: Sleep difficulties are common following mild TBI in children and are predictive of longer-term outcomes. Identifying children with sleep difficulties post-injury and providing support to facilitate sleep may improve their longer-term functioning. PMID- 27391451 TI - Future Papers. PMID- 27391448 TI - Patterns and Determinants of Double-Burden of Malnutrition among Rural Children: Evidence from China. AB - Chinese children are facing dual burden of malnutrition-coexistence of under-and over-nutrition. Little systematic evidence exists for explaining the simultaneous presence of under-and over-nutrition. This study aims to explore underlying mechanisms of under-and over-nutrition among children in rural China. This study used a nationwide longitudinal dataset of children (N = 5,017) from 9 provinces across China, with four exclusively categories of nutritional outcomes including under-nutrition (stunting and underweight), over-nutrition (overweight only including obesity), paradox (stunted overweight), with normal nutrition as reference. Multinomial logit models (Level-1: occasions; Level-2: children; Level 3: villages) were fitted which corrected for non-independence of observations due to geographic clustering and repeated observations of individuals. A mixture of risk factors at the individual, household and neighbourhood levels predicted under-and over-nutrition among children in rural China. Improved socioeconomic status and living in more urbanised villages reduced the risk of stunted overweight among rural children in China. Young girls appeared to have higher risk of under-nutrition, and the risk decreased with age more markedly than for boys up to age 5. From age 5 onwards, boys tended to have higher risk of under nutrition than girls. Girls aged around 12 and older were less likely to suffer from under-nutrition, while boys' higher risk of under-nutrition persisted throughout adolescence. Children were less likely to suffer from over-nutrition compared to normal nutrition. Boys tended to have an even lower risk of over nutrition than girls and the gender difference widened with age until adolescence. Our results have important policy implications that improving household economic status, in particular, maternal education and health insurance for children, and living environment are important to enhance rural children's nutritional status in China. Investments in early years of childhood can be effective to reduce gender inequality in nutritional health in rural China. PMID- 27391450 TI - Temporal and Spatial Variation of Soil Bacteria Richness, Composition, and Function in a Neotropical Rainforest. AB - The high diversity of tree species has traditionally been considered an important controller of belowground processes in tropical rainforests. However, soil water availability and resources are also primary regulators of soil bacteria in many ecosystems. Separating the effects of these biotic and abiotic factors in the tropics is challenging because of their high spatial and temporal heterogeneity. To determine the drivers of tropical soil bacteria, we examined tree species effects using experimental tree monocultures and secondary forests at La Selva Biological Station in Costa Rica. A randomized block design captured spatial variation and we sampled at four dates across two years to assess temporal variation. We measured bacteria richness, phylogenetic diversity, community composition, biomass, and functional potential. All bacteria parameters varied significantly across dates. In addition, bacteria richness and phylogenetic diversity were affected by the interaction of vegetation type and date, whereas bacteria community composition was affected by the interaction of vegetation type and block. Shifts in bacteria community richness and composition were unrelated to shifts in enzyme function, suggesting physiological overlap among taxa. Based on the observed temporal and spatial heterogeneity, our understanding of tropical soil bacteria will benefit from additional work to determine the optimal temporal and spatial scales for sampling. Understanding spatial and temporal variation will facilitate prediction of how tropical soil microbes will respond to future environmental change. PMID- 27391452 TI - Primary Signet-Ring Cell/Histiocytoid Carcinoma of the Eyelid: A "Binocle" Presentation of the "Monocle Tumor". AB - Primary cutaneous signet-ring cell carcinoma is a rare and aggressive neoplasm which diffusely involves dermis and subcutis of the eyelid or axillae. Neoplastic cells show a signet-ring cell or histiocytoid morphology in variable number, and can be found intermingled among collagen bundles, sparing the epidermis. This neoplasm typically appears in the eyelids of elderly men, in the form of a painless infiltration and swelling but with no other specific clinical feature, and frequently causes diagnostic retardation and worse prognosis. Frequent involvement of both eyelids of the same eye has given it the name of monocle tumor. Only 29 cases have been described in English literature to date, of which 7 developed metastases, mainly on regional lymph nodes. The authors present a case of involvement of contralateral eyelid, which has only been described previously in 2 cases. The immunohistochemical profile of the involvement in the contralateral eye, and the absence of other metastasis, suggest that it is locally spread from the initial lesion. However the possibility of being a second primary tumor or metastasis cannot be readily ruled out. PMID- 27391453 TI - Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas. AB - Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation. PMID- 27391454 TI - Neurotropic Gamma-Delta T-Cell Lymphoma With CD30-Positive Lymphoid Infiltrates. AB - Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a clonal proliferation of gamma-delta T cells with a cytotoxic phenotype that is typically characterized by an aggressive clinical course with ulcerative plaques or subcutaneous nodules. In this report, the authors describe a patient who developed an ulcerated tumor on the left upper extremity and painful papules and nodules on the right lower extremity. Interestingly, several of the papulonodules on the right lower extremity underwent spontaneous involution. A skin biopsy of the papulonodular lesion demonstrated a superficial and deep perivascular interstitial infiltrate with a population of pleomorphic enlarged CD30-positive T cells. These enlarged lymphocytes lacked expression of TCR beta, CD4, CD8, and the pan T-cell antigen CD7, but were positive for TCR gamma, supporting the diagnosis of PCGD-TCL. The patient rapidly developed pain and severe weakness in the left upper limb and MRI revealed extensive neurolymphomatosis of the left brachial plexus. The patient was treated with chemotherapy with complete remission achieved. Unfortunately, her response was transient and the patient relapsed and ultimately died due to her disease. In this article, the authors describe an extraordinary case of a CD30-positive PCGD-TCL to expand the histopathological spectrum of CD30-positive and gamma-delta-positive lymphoproliferative disorders. PMID- 27391455 TI - Osteonevus of Nanta Revisited: Clinicopathological Features of 33 Cases. PMID- 27391456 TI - Annular Lichenoid Dermatitis (of Youth) Immunohistochemical and Serological Evidence for Another Clinical Presentation of Borrelia Infection in Patients of Western Austria. AB - Annular lichenoid dermatitis of youth (ALDY) is a more recently described inflammatory disease of the skin of unknown etiology with clinical similarities to morphea. The authors clinically, histopathologically, and immunohistochemically investigated 14 biopsies from 12 patients in western Austria with this disease. There were 6 female and 6 male patients with solitary (n = 7) and multiple lesions (n = 5) affecting the trunk (n = 11), upper arm (n = 2), thigh (n = 1), and calf (n = 1). Clinically, early lesions were erythematous in nature leading to central paleness, scaling, wrinkling, dermal atrophy, slight pigmentation, and telangiectasia later on. Histopathologically, all specimens showed the typical features of ALDY with a superficial lichenoid process with sprinkling of lymphocytes along the basal cell layer and within the epidermis accompanied by mild fibrosis. Pigment incontinence, superficial fibrosis, and dilatation of superficial capillary vessels are prominent features in more advanced stages of disease. Immunohistologically, using a polyclonal antibody against Borrelia, 11/14 specimens revealed spirochetes, either vital (n = 4) or degenerated (n = 7), in close proximity to collagen bundles. Thirteen of 14 specimens in addition showed focal (n = 4) or clustered (n = 9) positivity for CD20 in the papillary dermis. Nine of 12 sera tested for Borrelia with an enzyme linked immunosorbent assay were positive. Lichen sclerosus et atrophicus and morphea have previously been reported to be possibly related to Borrelia infection. We postulate that a similar relationship to Borrelia infection may be true for ALDY implying that ALDY may be an early superficial stage of morphea. PMID- 27391457 TI - Atypical Spitzoid Neoplasms in Childhood: A Molecular and Outcome Study. AB - The natural history of atypical Spitz neoplasms remains poorly understood, resulting in significant patient and clinician anxiety. We sought to better characterize outcomes that correlated with molecular features by performing a prospective cohort study of pediatric atypical spitzoid neoplasms in which fluorescence in situ hybridization studies were obtained for diagnosis. Cases with sufficient tissue underwent additional retrospective assessment for translocations in ALK, NTRK1, BRAF, RET, and ROS1. Among 246 total patients assessed, 13% had a positive fluorescence in situ hybridization result. Follow-up data was available in 85 patients. Two patients had a recurrence of whom 1 had distant metastasis. Both patients had homozygous deletions in 9p21. Homozygous deletions in 9p21 significantly correlated with recurrence of disease (P = 0.027). Fifteen (36%) of 42 cases were found to have a kinase fusion protein. However, the presence of kinase fusions was nonprognostic of recurrence (P > 0.99). This study was limited by the availability and length of follow-up data and the number of adverse outcomes. The majority of atypical spitzoid neoplasms in childhood have indolent behavior. Although the subgroup of patients with homozygous deletions in 9p21 is at higher risk for aggressive clinical behavior, their prognosis seems considerably better than similarly staged conventional melanoma. PMID- 27391458 TI - Mitotic Activity in Juvenile Benign Nevi. AB - Melanocytic nevi are submitted for histological evaluation primarily to exclude a malignant process. Mitotic figures are one of the factors used in this assessment. However, there is a lack of data on mitotic activity in juvenile benign nevi. The authors assessed 114 cases of benign melanocytic nevi in children aged 0-15 (inclusive) years old by counting the mitoses present in 2 sections of hematoxylin and eosin-stained tissue. The authors then calculated the proportion of cases in which mitotic activity was present, and the average number of mitoses per case for each age group to get the mitotic rate. The authors found that there was at least 1 mitoses present in 40.4% of cases, and that the mitotic rate decreases in older children compared with younger children. This highlights the need for careful consideration of the significance of a mitotic figure in juvenile pigmented lesions, to ensure the lesion is not overinterpreted as malignant. PMID- 27391459 TI - Sebocyte-Like Melanocytes-Additional Relevant (and Behind the Scenes) Historical Information. PMID- 27391460 TI - High Relative Expression of Pannexin 3 (PANX3) in an Axillary Sweat Gland Carcinoma With Osteosarcomatous Transformation. AB - Primary cutaneous sweat gland carcinomas (SGCs) are rare tumors that commonly involve axillae, have a high local recurrence rate, and rarely show sarcomatoid transformation. A 68-year-old man presented with rapid enlargement of a previously stable, asymptomatic pea-sized nodule in the left axilla. Initial excision (with positive surgical margins) at another institution showed characteristic histologic features of a high-grade osteosarcoma and molecular analysis using a 92-gene real-time quantitative reverse transcription-polymerase chain reaction assay confirmed a diagnosis of osteosarcoma with 96% certainty. Notably, the molecular assay demonstrated consistently high relative expression of pannexin 3 (PANX3), a gene involved in normal osteoblast differentiation which, when highly expressed, strongly predicts osteosarcoma per the assay's algorithm. However, on further histologic review, the tumor also contained focal cystic areas, nests, and ducts composed of malignant epithelial cells reminiscent of SGC; these areas directly transitioned into the osteosarcomatous component and were strongly positive for pancytokeratin, CK7, and p63. Within 2 weeks, the lesion recurred and grew rapidly, prompting complete resection, histologic sections of which showed high-grade osteosarcoma without residual epithelial elements. This is the fifth report, to our knowledge, of osteosarcomatous transformation in a SGC, and the only report to date including molecular data. This case demonstrates that osteosarcoma arising from a SGC has a similar molecular profile to de novo primary osteosarcoma of bone. It also emphasizes the importance of histopathologic findings as the established diagnostic gold standard and the need to interpret molecular results within the clinical context. PMID- 27391461 TI - Retraction: Atorvastatin Improves Survival in Septic Rats: Effect on Tissue Inflammatory Pathway and on Insulin Signaling. PMID- 27391462 TI - MLVA Typing of Streptococcus pneumoniae Isolates with Emphasis on Serotypes 14, 9N and 9V: Comparison of Previously Described Panels and Proposal of a Novel 7 VNTR Loci-Based Simplified Scheme. AB - Streptococcus pneumoniae remains as an important cause of community-acquired bacterial infections, and the nasopharynx of asymptomatic carriers is the major reservoir of this microorganism. Pneumococcal strains of serotype 14 and serogroup 9 are among the most frequently isolated from both asymptomatic carriers and patients with invasive disease living in Brazil. Internationally disseminated clones belonging to such serotypes have been associated with the emergence and spread of antimicrobial resistance in our setting, highlighting the need for epidemiological tracking of these isolates. In this scenario, Multiple Loci VNTR Analysis (MLVA) has emerged as an alternative tool for the molecular characterization of pneumococci, in addition to more traditional techniques such as Multi-Locus Sequence Typing (MLST) and Pulsed-Field Gel Electrophoresis (PFGE). In the present study, 18 VNTR loci, as well as other previously described reduced MLVA panels (7 VNTR loci), were evaluated as tools to characterize pneumococcal strains of serotypes 14, 9N and 9V belonging to international and regional clones isolated in Brazil. The 18 VNTR loci panel was highly congruent with MLST and PFGE, being also useful for indicating the genetic relationship with international clones and for discriminating among strains with indistinguishable STs and PFGE profiles. Analysis of the results also allowed deducing a novel shorter 7 VNTR loci panel, keeping a high discriminatory power for isolates of the serotypes investigated and a high congruence level with MLST and PFGE. The newly proposed simplified panel was then evaluated for typing pneumococcal strains of other commonly isolated serotypes. The results indicate that MLVA is a faster and easier to perform, reliable approach for the molecular characterization of S. pneumoniae isolates, with potential for cost-effective application, especially in resource-limited countries. PMID- 27391463 TI - Arch structure is associated with unique joint work, relative joint contributions and stiffness during landing. AB - To examine lower extremity joint contributions to a landing task in high-(HA) and low-arched (LA) female athletes by quantifying vertical stiffness, joint work and relative joint contributions to landing. METHODS: Twenty healthy female recreational athletes (10 HA and 10 LA) performed five barefoot drop landings from a height of 30cm. Three-dimensional kinematics (240Hz) and ground reaction forces (960Hz) were recorded simultaneously. Vertical stiffness, joint work values and relative joint work values were calculated using Visual 3D and MatLab. RESULTS: HA athletes had significantly greater vertical stiffness compared to LA athletes (p=0.013). Though no differences in ankle joint work were observed (p=0.252), HA athletes had smaller magnitudes of knee (p=0.046), hip (p=0.019) and total lower extremity joint work values (p=0.016) compared to LA athletes. HA athletes had greater relative contributions of the ankle (p=0.032) and smaller relative contributions of the hip (p=0.049) compared to LA athletes. No differences in relative contributions of the knee were observed (p=0.255). CONCLUSIONS: These findings demonstrate that aberrant foot structure is associated with unique contributions of lower extremity joints to load attenuation during landing. These data may provide insight into the unique injury mechanisms associated with arch height in female athletes. PMID- 27391464 TI - Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome). AB - PURPOSE: To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). METHODS: We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. RESULTS: Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%. CONCLUSIONS: SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions. PMID- 27391465 TI - Inhibition of Pig Phosphoenolpyruvate Carboxykinase Isoenzymes by 3 Mercaptopicolinic Acid and Novel Inhibitors. AB - There exist two isoforms of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in pig populations that differ in a single amino acid (Met139Leu). The isoenzymes have different kinetic properties, affecting more strongly the Km and Vmax of nucleotides. They are associated to different phenotypes modifying traits of considerable economic interest. In this work we use inhibitors of phosphoenolpyruvate carboxykinase activity to search for further differences between these isoenzymes. On the one hand we have used the well-known inhibitor 3 mercaptopicolinic acid. Its inhibition patterns were the same for both isoenzymes: a three-fold decrease of the Ki values for GTP in 139Met and 139Leu (273 and 873 MUM, respectively). On the other hand, through screening of a chemical library we have found two novel compounds with inhibitory effects of a similar magnitude to that of 3-mercaptopicolinic acid but with less solubility and specificity. One of these novel compounds, (N'1-({5-[1-methyl-5 (trifluoromethyl)-1H-pyrazol-3-yl]-2-thienyl}methylidene)-2,4-dichlorobenzene-1 carbohydrazide), exhibited significantly different inhibitory effects on either isoenzyme: it enhanced threefold the apparent Km value for GTP in 139Met, whereas in 139Leu, it reduced it from 99 to 69 MUM. The finding of those significant differences in the binding of GTP reinforces the hypothesis that the Met139Leu substitution affects strongly the nucleotide binding site of PEPCK-C. PMID- 27391466 TI - Beyond the dollar: Influence of sociodemographic marginalization on surgical resection, adjuvant therapy, and survival in patients with pancreatic cancer. AB - BACKGROUND: The single-payer universal health care system in Ontario, Canada creates a setting with reduced socioeconomic barriers to treatment. Herein, the authors sought to elucidate the influence of sociodemographic marginalization on receipt of pancreatectomy, overall survival (OS), and receipt of adjuvant treatment among patients diagnosed with pancreatic cancer at the population level using an observational cohort study design. METHODS: Patients diagnosed with pancreatic cancer in Ontario between January 2005 and January 2010 were identified using the provincial cancer registry and linked to administrative databases. Census data obtained from each patient's postal code were used as a proxy for that patient's median income, residential instability, material deprivation, ethnic concentration, and dependency (percentage aged <15 years, aged >65 years, and unemployed). Surgical specimen pathology reports were abstracted for histopathology and margin status. Independent predictors of undergoing pancreatectomy, OS after surgical resection, and receipt of adjuvant treatment were identified by logistic regression and Cox proportional hazards analysis. RESULTS: Of the 6296 patients diagnosed with pancreatic cancer, 820 (13%) underwent resection of their tumor. Increasing levels of residential instability (odds ratio [OR], 0.86; 95% confidence interval [95% CI], 0.80-0.94) and material deprivation (OR, 0.86; 95% CI, 0.79-0.94) predicted a decreased likelihood of undergoing surgical resection. Patients living in rural areas (OR, 0.68; 95% CI, 0.51-0.91) and those living in urban areas with lower incomes (OR range, 0.49-0.77) were found to have a lower likelihood of undergoing surgical resection compared with patients in the urban areas with the highest income. After surgical resection, an association between sociodemographic marginalization with OS or receipt of adjuvant treatment was not identified. CONCLUSIONS: Sociodemographic marginalization exerts its influence early in the pancreatic cancer care continuum, and appears to be associated more with which patients undergo surgical resection than the receipt of adjuvant treatment. Cancer 2016;122:3175-82. (c) 2016 American Cancer Society. PMID- 27391467 TI - Differential Matrix Metalloprotease (MMP) Expression Profiles Found in Aged Gingiva. AB - The periodontium undergoes age-related cellular and clinical changes, but the involved genes are not yet known. Here, we investigated age-related genetic changes in gingiva at the transcriptomic level. Genes that were differentially expressed between young and old human gingiva were identified by RNA sequencing and verified by real-time PCR. A total of 1939 mRNA transcripts showed significantly differential expression between young and old gingival tissues. Matrix metalloprotease (MMP) regulation was the top pathway involved in gingival aging. MMP3, MMP9, MMP12, and MMP13 were upregulated in old gingival tissues, concomitantly with interleukin-1 beta (IL1B) expression. In vitro experiments using human gingival fibroblasts (hGFs) showed that MMP12 was upregulated in old hGFs compared to young hGFs. Moreover, the MMP3, MMP9 and IL1B levels were more highly stimulated by infection with the oral bacterium, Fusobacterium nucleatum, in old hGFs compared to young hGFs. Collectively, these findings suggest that, in gingiva, the upregulation of MMP12 may be a molecular hallmark of natural aging, while the upregulations of MMP3, MMM9, and IL1B may indicate externally (e.g., infection)-induced aging. These findings contribute to our understanding of the molecular targets involved in gingival aging. PMID- 27391468 TI - Presence of Native Prey Does Not Divert Predation on Exotic Pests by Harmonia axyridis in Its Indigenous Range. AB - In China, two invasive pests, Bemisia tabaci MEAM1 (Gennadius) and Frankliniella occidentalis (Pergande), often co-occur with the native pest, Aphis gossypii (Glover), on plants of Malvaceae and Cucurbitaceae. All three are preyed on by the native ladybird, Harmonia axyridis (Pallas); however, the native predator might be expected to prefer native prey to the exotic ones due to a shared evolutionary past. In order to clarify whether the presence of native prey affected the consumption of these two invasive species by the native predator, field-cage experiments were conducted. A duplex qPCR was used to simultaneously detect both non-native pests within the gut of the predator. H. axyridis readily accepted both invasive prey species, but preferred B. tabaci. With all three prey species available, H. axyridis consumption of B. tabaci was 39.3+/-2.2% greater than consumption of F. occidentalis. The presence of A. gossypii reduced (by 59.9% on B. tabaci, and by 60.6% on F. occidentalis), but did not stop predation on the two exotic prey when all three were present. The consumption of B. tabaci was similar whether it was alone or together with A. gossypii. However, the presence of aphids reduced predation on the invasive thrips. Thus, some invasive prey may be incorporated into the prey range of a native generalist predator even in the presence of preferred native prey. PMID- 27391469 TI - Oxidation of Sa2+-Binding Domain of NADPH Oxidase 5 (NOX5): Toward Understanding the Mechanism of Inactivation of NOX5 by ROS. AB - NOX5 protein, one of the most active generators of reactive oxygen species (ROS), plays an important role in many processes, including regulation of cell growth, death and differentiation. Because of its central role in ROS generation, it needs to be tightly regulated to guarantee cellular homeostasis. Contrary to other members of NADPH-oxidases family, NOX5 has its own regulatory calcium binding domain and thus could be activated directly by calcium ions. While several mechanisms of activation have been described, very little is known about the mechanisms that could prevent the overproduction of ROS by NOX5. In the present study using calorimetric methods and circular dichroism we found that oxidation of cysteine and methionine residues of NOX5 decreases binding of Ca2+ ions and perturbs both secondary and tertiary structure of protein. Our data strongly suggest that oxidation of calcium-binding domain of NOX5 could be implicated in its inactivation, serving as a possible defense mechanism against oxidative stress. PMID- 27391470 TI - Performance of the SRK/T formula using A-Scan ultrasound biometry after phacoemulsification in eyes with short and long axial lengths. AB - BACKGROUND: The SRK/T formula is one of the third generation IOL calculation formulas. The purpose of this study was to evaluate the performance of the SRK/T formula in predicting a target refraction +/-1.0D in short and long eyes using ultrasound biometry after phacoemulsification. METHODS: The present study was a retrospective analysis, which included 38 eyes with an AL < 22.0 mm (short AL), and 62 eyes >=24.6 mm (long AL) that underwent uncomplicated phacoemulsification. Preoperative AL was measured by ultrasound biometry and SRK/T formula was used for IOL calculation. Three different IOLs were implanted in the capsular bag. The prediction error was defined as the difference between the achieved postoperative refraction, and attempted predicted target refraction. Statistical analysis was performed with SPSS V21. RESULTS: In short ALs, the mean age was 65.13 +/- 9.49 year, the mean AL was 21.55 +/- 0.45 mm, the mean K1 and K2 were 45.76 +/- 1.77D and 46.09 +/- 1.61D, the mean IOL power was 23.96 +/- 1.92D, the mean attempted (predicted) value was 0.07 +/- 0.26D, the mean achieved value was 0.07 +/- 0.63 D, the mean PE was 0.01 +/- 0.60D, and the MAE was 0.51 +/- 0.31D. A significant positive relationship with AL and K1, K2, IOL power and a strong negative relationship with PE and achieved postoperative was found. In long ALs, the mean age was 64.05 +/- 7.31 year, the mean AL was 25.77 +/- 1.64 mm, the mean K1 and K2 were 42.20 +/- 1.57D and 42.17 +/- 1.68D, the mean IOL power was 15.79 +/- 5.17D, the mean attempted value was -0.434 +/- 0.315D, the mean achieved value was -0.42 +/- 0.96D, the mean PE was -0.004 +/- 0.93D, the MAE was 0.68 +/- 0.62D. A significant positive relationship with AL and K1, K2 and a significant positive relationship with PE and achieved value, otherwise a negative relationship with AL and IOL power was found. There was a little tendency towards hyperopic for short ALs and myopic for long ALs. The majority of eyes (94.74 %) for short ALs and (70.97 %) for long ALs were within +/-1 D of the predicted refractive error. No significant relationship with PE and IOL types, AL, K1, K2, IOL power, and attempted value, besides with MAE and AL, K1, K2, age, attempted, achieved value were found in both groups. CONCLUSION: The SRK/T formula performs well and shows good predictability in eyes with short and long axial lengths. PMID- 27391471 TI - Expectations and needs of patients with a chronic disease toward self-management and eHealth for self-management purposes. AB - BACKGROUND: Self-management is considered as an essential component of chronic care by primary care professionals. eHealth is expected to play an important role in supporting patients in their self-management. For effective implementation of eHealth it is important to investigate patients' expectations and needs regarding self-management and eHealth. The objectives of this study are to investigate expectations and needs of people with a chronic condition regarding self management and eHealth for self-management purposes, their willingness to use eHealth, and possible differences between patient groups regarding these topics. METHODS: Five focus groups with people with diabetes (n = 14), COPD (n = 9), and a cardiovascular condition (n = 7) were conducted in this qualitative research. Separate focus groups were organized based on patients' chronic condition. The following themes were discussed: 1) the impact of the chronic disease on patients' daily life; 2) their opinions and needs regarding self-management; and 3) their expectations and needs regarding, and willingness to use, eHealth for self-management purposes. A conventional content analysis approach was used for coding. RESULTS: Patient groups seem to differ in expectations and needs regarding self-management and eHealth for self-management purposes. People with diabetes reported most needs and benefits regarding self-management and were most willing to use eHealth, followed by the COPD group. People with a cardiovascular condition mentioned having fewer needs for self-management support, because their disease had little impact on their life. In all patient groups it was reported that the patient, not the care professional, should choose whether or not to use eHealth. Moreover, participants reported that eHealth should not replace, but complement personal care. Many participants reported expecting feelings of anxiety by doing measurement themselves and uncertainty about follow-up of deviant data of measurements. In addition, many participants worried about the implementation of eHealth being a consequence of budget cuts in care. CONCLUSION: This study suggests that aspects of eHealth, and the way in which it should be implemented, should be tailored to the patient. Patients' expected benefits of using eHealth to support self-management and their perceived controllability over their disease seem to play an important role in patients' willingness to use eHealth for self-management purposes. PMID- 27391472 TI - Management and outcome of spontaneous subaponeurotic fluid collections in infants: the Hospital for Sick Children experience and review of the literature. AB - OBJECTIVE Spontaneous subaponeurotic fluid collection (SSFC) is an uncommon and newly described entity of unknown etiology, observed in infants less than 1 year of age. The authors report on series of infants who presented to the Hospital for Sick Children (HSC) with SSFC, focusing on the natural history of this condition. METHODS Data from the Hospital for Sick Children were retrospectively reviewed for the period between January 2004 and June 2015. Patient age and sex, birth history, medical history, laboratory findings, and symptoms were reviewed. SSFC location, imaging characteristics, management, and outcome were also analyzed. A MEDLINE and Embase literature search was performed on the condition, yielding previously reported cases of SSFC in the English language. RESULTS Nine cases involving patients who presented with SSFC during the study period were identified. The patients were 4 male and 5 female infants (age range 5 weeks to 11 months). All cases of SSFC developed spontaneously over a period of days, and the infants had no history of injuries, trauma, or hair manipulation in the immediate period preceding the development of the subgaleal collections. Six patients underwent remote forceps- or vacuum-assisted instrumented births, although none of the patients developed scalp collections or skin discoloration immediately after birth. All of the cases were managed conservatively on an outpatient (6 cases) or inpatient (3 cases) basis. In 1 case, the size of the fluid collection fluctuated over 4 months, but in all of the cases, the collections resolved spontaneously without structural or infectious complications. CONCLUSIONS This is the largest series describing SSFC to date and summarizes 9 cases managed at a large academic neurosurgical center. Although the specific pathophysiology of SSFC remains unknown, in some cases the condition may be associated with a remote history of instrumented delivery. SSFC occurs spontaneously without immediate preceding trauma, and an extensive hematology or child abuse workup is not necessary. A conservative approach with outpatient follow-up is advocated. PMID- 27391473 TI - Disrupting differential hypoxia in peripheral veno-arterial extracorporeal membrane oxygenation. AB - Patients receiving circulatory support with peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are at risk of developing differential hypoxia. This phenomenon occurs in patients with concomitant respiratory failure. Poorly oxygenated blood, ejected into the ascending aorta from the left ventricle, competes with retrograde flow from the ECMO circuit, potentially causing myocardial and cerebral ischaemia. In a recent Critical Care article, Hou et al. use an animal model of peripheral VA-ECMO to study the physiology of differential hypoxia. Their findings support a dual circuit hypothesis, and show how different cannulation strategies can disrupt the two circuits. In particular, strategies that increase venous oxygen saturations in the pulmonary artery can have a large effect on oxygenation saturation in the ascending aorta. The authors provide evidence supporting the use of veno-arterial venous ECMO in patients who require peripheral VA-ECMO but have simultaneous respiratory failure. PMID- 27391475 TI - Evaluation of the left and right ventricular systolic and diastolic function in asthmatic children. AB - BACKGROUND: Asthma is the most common cause of respiratory disorders among children. We aimed to investigate left (LV) and right (RV) ventricular function in asthmatic children as detected by conventional and tissue Doppler echocardiography. METHODS: Fifty pediatric patients with asthma and forty healthy children were studied. Pulmonary function tests, electrocardiography and echocardiographic examinations were performed on all children. RESULTS: Rate corrected velocity of circumferential fiber shortening (VCFc) (p = 0.044), the ratio between heights of early and late diastolic flow velocity peaks (E/A) (p = 0.019) and LV end-systolic wall stress (ESWSm) was lower (p = 0.003), RV stroke volume (SV) (p = 0.002), LV SV (p = 0.001), tricuspid annular plane systolic excursion (TAPSE) (p = 0.034), tricuspid annular peak velocity during systole (S') (p = 0.022), tricuspid and mitral early diastolic velocities (E') (p = 0.012, p = 0.003 respectively) were lower in asthmatic children than controls. The mitral valve ejection time (ET) was high in asthmatic group (p = 0.027). FEV1 was positively correlated with isovolumetric relaxation time (IVRT) (p = 0.018) (r = 0.382) and mitral ET (p = 0.018) (r = 0.381). PEF was negatively correlated with the RV work index (p = 0.032) (r = -0.348) and LV work index (p = 0.005) (r = -0.457). CONCLUSION: Although cardiac systolic function was found to be impaired in asthmatic patients, contrary to the literature, diastolic dysfunction was not observed in these patients, even by tissue Doppler imaging, and this finding may be attributed to using inhaled corticosteroid. PMID- 27391474 TI - Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease. AB - BACKGROUND: Neurodegeneration is believed to be the primary cause of permanent, long-term disability in patients with multiple sclerosis. The cause of neurodegeneration in multiple sclerosis appears to be multifactorial. One mechanism that has been implicated in the pathogenesis of neurodegeneration in multiple sclerosis is the targeting of neuronal and axonal antigens by autoantibodies. Multiple sclerosis patients develop antibodies to the RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which is enriched in neurons. We hypothesized that anti-hnRNP A1 antibodies would contribute to neurodegeneration in an animal model of multiple sclerosis. METHODS: Following induction of experimental autoimmune encephalomyelitis (EAE) by direct immunization with myelin oligodendrocyte glycoprotein, mice were injected with anti-hnRNP A1 or control antibodies. Animals were examined clinically, and the central nervous system (CNS) tissues were tested for neurodegeneration with Fluoro-Jade C, a marker of degenerating neural elements. RESULTS: Injection of anti-hnRNP A1 antibodies in mice with EAE worsened clinical disease, altered the clinical disease phenotype, and caused neurodegeneration preferentially in the ventral spinocerebellar tract and deep white matter of the cerebellum in the CNS. Neurodegeneration in mice injected with hnRNP A1-M9 antibodies compared to control groups was consistent with "dying back" axonal degeneration. CONCLUSIONS: These data suggest that antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in immune-mediated disease of the CNS. PMID- 27391476 TI - Cytotoxic potential of selected medicinal plants in northeast Brazil. AB - BACKGROUND: Great biodiversity is a highlight of Brazilian flora. In contrast, the therapeutic potentialities of most species used in folk medicine remain unknown. Several of these species are commonly used to treat cancer. In this study, we investigated the cytotoxic activity of 18 plants from 16 families that are found in the northeast region of Brazil. METHODS: The following species were studied: Byrsonima sericea DC. (Malpighiaceae), Cupania impressinervia Acev. Rodr. var. (revoluta) Radlk (Sapindaceae), Duranta repens Linn. (Verbenaceae), Helicostylis tomentosa (Poepp. & Endl) Rusby (Moraceae), Himatanthus bracteatus (A.DC.) Woodson (Apocynaceae), Ipomoea purga (Wender.) Hayne (Convolvulaceae), Ixora coccinea Linn. (Rubiaceae), Mabea piriri Aubl. (Euphorbiaceae), Miconia minutiflora (Melastomataceae), Momordica charantia L. (Cucurbitaceae), Ocotea glomerata (Nees) Mez (Lauraceae), Ocotea longifolia Kunth (Oreodaphne opifera Mart. Nees) (Lauraceae), Pavonia fruticosa (Mill.) Fawc. & Rendle (Malvaceae), Psychotria capitata Ruiz & Pav. (Rubiaceae), Schefflera morototoni (Aubl.) Maguire, Steyerm. & Frodin (Araliaceae), Solanum paludosum Moric. (Solanaceae), Xylopia frutescens Aubl. (Annonaceae) and Zanthoxylum rhoifolium Lam. (Rutaceae). Their dried leaves, stems, flowers or fruits were submitted to different solvent extractions, resulting in 55 extracts. After incubating for 72 h, the cytotoxicity of each extract was tested against tumor cell lines using the alamar blue assay. RESULTS: The B. sericea, D. repens, H. bracteatus, I. purga, I. coccinea, M. piriri, O. longifolia and P. capitata extracts demonstrated the most potent cytotoxic activity. The chloroform soluble fractions of D. repens flowers and the hexane extract of I. coccinea flowers led to the isolation of quercetin and a mixture of alpha- and beta-amyrin, respectively, and quercetin showed moderate cytotoxic activity. CONCLUSION: The B. sericea, D. repens, H. bracteatus, I. purga, I. coccinea, M. piriri, O. longifolia and P. capitata plants were identified as having potent cytotoxic effects. Further investigations are required to determine the mechanisms of cytotoxicity exhibited and their in vivo activities. This work reinforces the need to understand the therapeutics potentialities of Brazilian medicinal plants. PMID- 27391478 TI - Sleep, Fatigue and Quality of Life: A Comparative Analysis among Night Shift Workers with and without Children. AB - INTRODUCTION: The reversal of the natural cycle of wakefulness and sleep may cause damage to the health of workers. However, there are few studies evaluating sleep, fatigue and quality of life of night shift workers considering the influence of small children on these variables. AIMS: Evaluate the sleep time, fatigue and quality of life of night shift workers and verify the relationship between these variables with the presence or absence of children in different age groups. METHODS: Were evaluated 78 mens shiftworkers, with or without children. Group 1, workers without children (G1-NC), group 2, workers with children pre school age (G2-PS) and group 3, workers with children school age (G3-S). The sleep time (ST), sleep efficiency (SE), sleep latency (SL) and maximum time awake (MTA) were recorded by actigraphy. The risk of being fatigued at work was estimated by risk index for fatigue (RIF). RESULTS: The G1-NC showed a longer ST on working days and when evaluated only the first nights shift, after day off (p<0,005). This sample, the age of the children did not influence the sleep time these workers. The MTA on day off was lower in the workers from G2-PS. The RIF was lower on G1-NC in the first nights shift compared to the other groups. CONCLUSION: In this research, workers without children had higher sleep time during the working days. These workers also were less likely to feel fatigued during night work than workers with children, regardless of age these children. PMID- 27391477 TI - Elevated cerebrovascular resistance index is associated with cognitive dysfunction in the very-old. AB - INTRODUCTION: Age-related vascular changes, including blood pressure elevation and cerebral blood flow (CBF) reduction, are associated with cognitive decline and Alzheimer's disease (AD). Evidence suggests that the relationship between blood pressure and dementia risk varies between younger and older samples within the elderly population. METHODS: We examined the relationship between mean arterial pressure (MAP), CBF, and cognition in young-old (60 to 75 years of age) versus very-old (80+ years of age) adults. Fifty-eight non-demented older adults completed an arterial spin labeling MRI scan, and an index of cerebrovascular resistance (CVRi) was estimated for each participant by calculating the ratio of MAP and CBF. RESULTS: Results demonstrated a similar negative relationship between MAP and CBF across both age groups. However, very-old participants exhibited elevated CVRi and reduced CBF compared to young-old participants in regions implicated in AD and cerebral small vessel disease. Furthermore, significant age by CVRi interactions revealed that elevated CVRi in the thalamus was inversely related to verbal fluency performance in the very-old group. CONCLUSIONS: Findings support CVRi as a potential vascular biomarker and suggest that regionally-specific vascular changes may contribute to cognitive decline, particularly in the very-old. PMID- 27391480 TI - Base rate comparison of suboptimal scores on the RBANS effort scale and effort index in Parkinson's disease. AB - OBJECTIVE: The effort index (EI) and the effort scale are commonly used embedded effort indicators on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This investigation examined the rates of suboptimal scores on the EI and effort scale in a Parkinson's disease (PD) sample. METHOD: One hundred and sixty-three participants who have been diagnosed with PD by a board-certified neurologist were included in the study. The base rate of suboptimal scores on the EI and effort scale was calculated for the entire group. RESULTS: On average, participants were 66.8 years of age (SD = 9.5) and had a mean education of 13.5 years (SD = 2.79). The mean Mini-Mental State Examination score was 27.0 (SD = 3.1). Overall, 8% of participants scored below the cut-off for optimal performance on the EI while 62.6% performed in the suboptimal range for the effort scale. CONCLUSION: The utility of the EI and the effort scale in PD populations warrants further examination. Additionally, results demonstrate the need for validation of embedded RBANS effort measures in various disease populations. PMID- 27391479 TI - The Circular RNA Cdr1as Act as an Oncogene in Hepatocellular Carcinoma through Targeting miR-7 Expression. AB - CircRNAs are a class of endogenous RNA that regulates gene expression at the post transcriptional or transcriptionallevel through interacting with other molecules or microRNAs. Increasing studies have demonstrated that circRNAs play a crucial role in biology processes. CircRNAs are proved as potentialbiomarkers in many diseases including cancers. However, the role of Cdr1as in Hepatocellular carcinoma (HCC) remains to be elucidated. We demonstrated that Cdr1as expression was upregulated in HCC tissues compared with the adjacent non-tumor tissues. In addtion, miR-7 expression was downregulated in HCC tissues compared with the adjacent non-tumor tissues. Moreover, the expression level of miR-7 was inversely correlated with that in HCC tissues. Knockdown of Cdr1as suppressed the HCC cell proliferation and invasion. Overexpression of miR-7 inhibited the HCC cell proliferation and invasion. Overexpression of miR-7 could suppress the direct target gene CCNE1 and PIK3CD expression. Knockdown of Cdr1as suppressed the expression of miR-7 and also inhibited the CCNE1 and PIK3CD expression. Furthermore, knockdown of Cdr1as suppressed the HCC cell proliferation and invasion through targeting miR-7. These data suggested that Cdr1as acted as an oncogene partly through targeting miR-7 in HCC. PMID- 27391481 TI - Temporal Non-Local Means Filtering Reveals Real-Time Whole-Brain Cortical Interactions in Resting fMRI. AB - Intensity variations over time in resting BOLD fMRI exhibit spatial correlation patterns consistent with a set of large scale cortical networks. However, visualizations of this data on the brain surface, even after extensive preprocessing, are dominated by local intensity fluctuations that obscure larger scale behavior. Our novel adaptation of non-local means (NLM) filtering, which we refer to as temporal NLM or tNLM, reduces these local fluctuations without the spatial blurring that occurs when using standard linear filtering methods. We show examples of tNLM filtering that allow direct visualization of spatio temporal behavior on the cortical surface. These results reveal patterns of activity consistent with known networks as well as more complex dynamic changes within and between these networks. This ability to directly visualize brain activity may facilitate new insights into spontaneous brain dynamics. Further, temporal NLM can also be used as a preprocessor for resting fMRI for exploration of dynamic brain networks. We demonstrate its utility through application to graph-based functional cortical parcellation. Simulations with known ground truth functional regions demonstrate that tNLM filtering prior to parcellation avoids the formation of false parcels that can arise when using linear filtering. Application to resting fMRI data from the Human Connectome Project shows significant improvement, in comparison to linear filtering, in quantitative agreement with functional regions identified independently using task-based experiments as well as in test-retest reliability. PMID- 27391482 TI - Social Withdrawal Behaviour at One Year of Age Is Associated with Delays in Reaching Language Milestones in the EDEN Mother-Child Cohort Study. AB - OBJECTIVE: The aim of the study was to examine the relationship between social withdrawal behaviour at one year and motor and language milestones. MATERIALS AND METHODS: One-year old children from the EDEN French population-based birth cohort study (Study on the pre- and postnatal determinants of the child's development and prospective health Birth Cohort Study) were included. Social withdrawal at one year was assessed by trained midwives using the Alarm Distress BaBy (ADBB) scale. Midwives concurrently examined infants' motor and language milestones. Parents reported on child's psychomotor and language milestones, during the interview with the midwife. RESULTS: After adjusting for potential confounding factors, social withdrawal behaviour was significantly associated with concurrent delays in motor and language milestones assessed by the midwife or the parents. DISCUSSION: Higher scores on social withdrawal behaviour as assessed with the ADBB were associated with delays in reaching language milestones, and to a lesser extent with lower motor ability scores. Taking the contribution of social withdrawal behaviour into account may help understand the unfolding of developmental difficulties in children. PMID- 27391483 TI - Polymer Coatings of Cochlear Implant Electrode Surface - An Option for Improving Electrode-Nerve-Interface by Blocking Fibroblast Overgrowth. AB - Overgrowth of connective tissue and scar formation induced by the electrode array insertion increase the impedance and, thus, diminish the interactions between neural probes as like cochlear implants (CI) and the target tissue. Therefore, it is of great clinical interest to modify the carrier material of the electrodes to improve the electrode nerve interface for selective cell adhesion. On one side connective tissue growth needs to be reduced to avoid electrode array encapsulation, on the other side the carrier material should not compromise the interaction with neuronal cells. The present in vitro-study qualitatively and quantitatively characterises the interaction of fibroblasts, glial cells and spiral ganglion neurons (SGN) with ultrathin poly(N,N-dimethylacrylamide) (PDMAA), poly(2-ethyloxazoline) (PEtOx) and poly([2 methacryloyloxy)ethyl]trimethylammoniumchlorid) (PMTA) films immobilised onto glass surfaces using a photoreactive anchor layer. The layer thickness and hydrophilicity of the polymer films were characterised by ellipsometric and water contact angle measurement. Moreover the topography of the surfaces was investigated using atomic force microscopy (AFM). The neuronal and non-neuronal cells were dissociated from spiral ganglions of postnatal rats and cultivated for 48 h on top of the polymer coatings. Immunocytochemical staining of neuronal and intermediary filaments revealed that glial cells predominantly attached on PMTA films, but not on PDMAA and PEtOx monolayers. Hereby, strong survival rates and neurite outgrowth were only found on PMTA, whereas PDMAA and PEtOx coatings significantly reduced the SG neuron survival and neuritogenesis. As also shown by scanning electron microscopy (SEM) SGN strongly survived and retained their differentiated phenotype only on PMTA. In conclusion, survival and neuritogenesis of SGN may be associated with the extent of the glial cell growth. Since PMTA was the only of the polar polymers used in this study bearing a cationic charge, it can be assumed that this charge favours adhesion of both glial cells and SG neurons glial cells and SGN. PMID- 27391485 TI - Bioturbation by the Fungus-Gardening Ant, Trachymyrmex septentrionalis. AB - Soil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of different colored sand. The amount of each color of sand deposited on the surface was determined from April to November 2015. In November, colonies were excavated and the color and amount of sand deposited below ground (mostly as backfill in chambers) was determined. Extrapolated to one ha, T. septentrionalis deposited 800 kg of sand per annum on the surface, and an additional 200 kg (17% of the total excavated) below ground. On average, this mixes 1.3% of the sand from other layers within the top meter of soil per millennium, but this mixing is unlikely to be homogeneous, and probably occurs as "hotspots" in both horizontal and vertical space. Such mixing is discussed as a challenge to sediment dating by optically stimulated luminescence (OSL). PMID- 27391484 TI - Effect of glycemic index and carbohydrate intake on kidney function in healthy adults. AB - BACKGROUND: Replacing carbohydrate with protein acutely increases glomerular filtration rate (GFR) but is associated with faster, long-term kidney disease progression. The effects of carbohydrate type (i.e. glycemic index, GI) on kidney function are unknown. METHODS: We conducted an ancillary study of a randomized, crossover feeding trial in overweight/obese adults without diabetes or kidney disease (N = 163). Participants were fed each of four healthy, DASH-like diets for 5 weeks, separated by 2-week washout periods. Weight was kept constant. The four diets were: high GI (GI >=65) with high %carb (58 % kcal) (reference diet), low GI (<=45) with low %carb (40 % kcal), low GI with high %carb; and high GI with low %carb. Plasma was collected at baseline and after each feeding period. Study outcomes were cystatin C, beta2-microglobulin (beta2M), and estimated GFR based on cystatin C (eGFRcys). RESULTS: Mean (SD) age was 52 (11) years; 52 % were women; 50 % were black. At baseline, mean (SD) cystatin C, beta2M, and eGFRcys were 0.8 (0.1) mg/L, 1.9 (0.4) mg/L, and 104 (16) mL/min/1.73 m(2). Compared to the high GI/high %carb diet, reducing GI, %carb, or both increased eGFRcys by 1.9 mL/min/1.73 m(2) (95 % CI: 1.1, 2.7; P < 0.001), 3.0 mL/min/1.73 m(2) (1.9, 4.0; P < 0.001), and 4.5 mL/min/1.73 m(2) (3.5, 5.4; P < 0.001), respectively. Increases in eGFRcys from reducing GI were significantly associated with increases in eGFRcys from reducing %carb (P < 0.001). Results for cystatin C and beta2M reflected eGFRcys. CONCLUSIONS: Reducing GI increased GFR. Reducing %carb by increasing calories from protein and fat, also increased GFR. Future studies on GI should examine the long-term effects of this increase in GFR on kidney injury markers and clinical outcomes. TRIAL REGISTRATION: Clinical Trials.gov, number: NCT00608049 (first registered January 23, 2008). PMID- 27391487 TI - Optimizing Imaging Conditions for Demanding Multi-Color Super Resolution Localization Microscopy. AB - Single Molecule Localization super-resolution Microscopy (SMLM) has become a powerful tool to study cellular architecture at the nanometer scale. In SMLM, single fluorophore labels are made to repeatedly switch on and off ("blink"), and their exact locations are determined by mathematically finding the centers of individual blinks. The image quality obtainable by SMLM critically depends on efficacy of blinking (brightness, fraction of molecules in the on-state) and on preparation longevity and labeling density. Recent work has identified several combinations of bright dyes and imaging buffers that work well together. Unfortunately, different dyes blink optimally in different imaging buffers, and acquisition of good quality 2- and 3-color images has therefore remained challenging. In this study we describe a new imaging buffer, OxEA, that supports 3-color imaging of the popular Alexa dyes. We also describe incremental improvements in preparation technique that significantly decrease lateral- and axial drift, as well as increase preparation longevity. We show that these improvements allow us to collect very large series of images from the same cell, enabling image stitching, extended 3D imaging as well as multi-color recording. PMID- 27391486 TI - Hearing Impairment Affects Dementia Incidence. An Analysis Based on Longitudinal Health Claims Data in Germany. AB - Recent research has revealed an association between hearing impairment and dementia. The objective of this study is to determine the effect of hearing impairment on dementia incidence in a longitudinal study, and whether ear, nose, and throat (ENT) specialist care, care level, institutionalization, or depression mediates or moderates this pathway. The present study used a longitudinal sample of 154,783 persons aged 65 and older from claims data of the largest German health insurer; containing 14,602 incident dementia diagnoses between 2006 and 2010. Dementia and hearing impairment diagnoses were defined according to International Classification of Diseases, Tenth Revision, codes. We used a Kaplan Meier estimator and performed Cox proportional hazard models to explore the effect of hearing impairment on dementia incidence, controlling for ENT specialist care, care level, institutionalization, and depression. Gender, age, and comorbidities were controlled for as potential confounders. Patients with bilateral (HR = 1.43, p<0.001) and side-unspecified (HR = 1.20, p<0.001) hearing impairment had higher risks of dementia incidence than patients without hearing impairment. We found no significant effect for unilateral hearing impairment and other diseases of the ear. The effect of hearing impairment was only partly mediated through ENT specialist utilization. Significant interaction between hearing impairment and specialist care, care level, and institutionalization, respectively, indicated moderating effects. We discuss possible explanations for these effects. This study underlines the importance of the association between hearing impairment and dementia. Preserving hearing ability may maintain social participation and may reduce the burden associated with dementia. The particular impact of hearing aid use should be the subject of further investigations, as it offers potential intervention on the pathway to dementia. PMID- 27391488 TI - The Bioeffects Resulting from Prokaryotic Cells and Yeast Being Exposed to an 18 GHz Electromagnetic Field. AB - The mechanisms by which various biological effects are triggered by exposure to an electromagnetic field are not fully understood and have been the subject of debate. Here, the effects of exposing typical representatives of the major microbial taxa to an 18 GHz microwave electromagnetic field (EMF)were studied. It appeared that the EMF exposure induced cell permeabilisation in all of the bacteria and yeast studied, while the cells remained viable (94% throughout the exposure), independent of the differences in cell membrane fatty acid and phospholipid composition. The resulting cell permeabilisation was confirmed by detection of the uptake of propidium iodine and 23 nm fluorescent silica nanospheres using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Upon EMF exposure, the bacterial cell membranes are believed to become permeable through quasi-endocytosis processes. The dosimetry analysis revealed that the EMF threshold level required to induce the uptake of the large (46 nm) nanopsheres was between three and six EMF doses, with a specific absorption rate (SAR) of 3 kW/kg and 5 kW/kg per exposure, respectively, depending on the bacterial taxa being studied. It is suggested that the taxonomic affiliation and lipid composition (e.g. the presence of phosphatidyl-glycerol and/or pentadecanoic fatty acid) may affect the extent of uptake of the large nanospheres (46 nm). Multiple 18 GHz EMF exposures over a one-hour period induced periodic anomalous increases in the cell growth behavior of two Staphylococcus aureus strains, namely ATCC 25923 and CIP 65.8T. PMID- 27391489 TI - Chaparral Shrub Hydraulic Traits, Size, and Life History Types Relate to Species Mortality during California's Historic Drought of 2014. AB - Chaparral is the most abundant vegetation type in California and current climate change models predict more frequent and severe droughts that could impact plant community structure. Understanding the factors related to species-specific drought mortality is essential to predict such changes. We predicted that life history type, hydraulic traits, and plant size would be related to the ability of species to survive drought. We evaluated the impact of these factors in a mature chaparral stand during the drought of 2014, which has been reported as the most severe in California in the last 1,200 years. We measured tissue water potential, native xylem specific conductivity, leaf specific conductivity, percentage loss in conductivity, and chlorophyll fluorescence for 11 species in February 2014, which was exceptionally dry following protracted drought. Mortality among the 11 dominant species ranged from 0 to 93%. Total stand density was reduced 63.4% and relative dominance of species shifted after the drought. Mortality was negatively correlated with water potential, native xylem specific conductivity, and chlorophyll fluorescence, but not with percent loss in hydraulic conductivity and leaf specific conductivity. The model that best explained mortality included species and plant size as main factors and indicated that larger plants had greater survival for 2 of the species. In general, species with greater resistance to water-stress induced cavitation showed greater mortality levels. Despite adult resprouters typically being more vulnerable to cavitation, results suggest that their more extensive root systems enable them to better access soil moisture and avoid harmful levels of dehydration. These results are consistent with the hypothesis that short-term high intensity droughts have the strongest effect on mature plants of shallow-rooted dehydration tolerant species, whereas deep-rooted dehydration avoiding species fare better in the short-term. Severe droughts can drive changes in chaparral structure as a result of the differential mortality among species. PMID- 27391490 TI - Quantitative Analysis of Change in Intracranial Volume After Posterior Cranial Vault Distraction. AB - Posterior cranial vault distraction is considered to be more effective for increasing intracranial volume than fronto-orbital advancement or anterior cranial vault expansion, but the changes in intracranial volumes after posterior cranial vault distraction remain unclear. The changes in intracranial volume were investigated in patients of premature craniosynostosis treated by this technique. Seven patients, 3 boys and 4 girls aged from 5 months to 3 years 3 months (mean 23 months) at operation, with craniosynostosis underwent posterior cranial vault distraction at Juntendo University Hospital from 2011 to 2014. Patient characteristics, length of distraction, and pre- and postoperative computed tomography findings were reviewed. Total intracranial volume, including the supratentorial space and posterior cranial fossa, was measured using the workstation functions on three-dimensional computed tomography scans. Posterior distraction was performed without severe complications except in 2 patients requiring additional surgeries. The distraction length was 22.3 to 39 mm (mean 31 mm), the intracranial volume change was 144 to 281 mL (mean 192 mL), and the enlargement ratio of intracranial volume was 113% to 134% (mean 121%). The present quantitative analysis of intracranial volume change after posterior distraction showed greater increases in intracranial volume compared with previous reports. Furthermore, intracranial volumes in our patients became nearly normal and were maintained for the follow-up period (maximum 13 months). Posterior cranial vault distraction is very effective to increase cranial volume, so may be the first choice of treatment in patients of craniosynostosis. PMID- 27391491 TI - Evaluation of the Removal Bacteria on Failed Titanium Implants After Irradiation With Erbium-Doped Yttrium Aluminium Garnet Laser. AB - Peri-implantitis may occur because of biologic or mechanical factors. It can be treated by a variety of methods. The aim of the present study is to evaluate implant surface of failed oral titanium implants after being irradiated with erbium laser. PMID- 27391492 TI - Effects of Superpulsed, Low-Level Laser Therapy on Neurosensory Recovery of the Inferior Alveolar Nerve. AB - OBJECTIVE: The purpose of this investigation was to evaluate the therapeutic efficacy of superpulsed, low-level laser therapy (SLLLT) on neurosensory recovery of the inferior alveolar nerve (IAN) after oral surgical injury. BACKGROUND DATA: A survey of the literature reveals the uncertainty of outcomes for the surgical management of IAN injury and the efficacy of low-level laser therapy in the treatment of IAN injury. METHODS: In this study, the authors report the results for SLLLT in 57 patients affected by paresthesia of the lip, chin, gingival, and buccal regions. Each patient was subjected to 10 laser treatments, once a week, with a GaAs diode laser. Clinical neurosensory tests (soft touch, 2-point discrimination, pin prick, thermal test) and the visual analogue scale were used before every treatment to evaluate the extent of neurosensory recovery. RESULTS: The authors' results demonstrate that 83.3% of the patients had a significant neurosensory recovery, as evident in the objective and subjective tests. CONCLUSION: The results reported in this study indicate that SLLLT has the potential to improve neurosensory recovery in patients with IAN paresthesia. PMID- 27391493 TI - Immediate Loading of Tapered Implants Placed in Postextraction Sockets and Healed Sites. AB - OBJECTIVE: The aim of the present study was to compare the survival, stability, and complications of immediately loaded implants placed in postextraction sockets and healed sites. METHODS: Over a 2-year period, all patients presenting with partial or complete edentulism of the maxilla and/or mandible (healed site group, at least 4 months of healing after tooth extraction) or in need of replacement of nonrecoverable failing teeth (postextraction group) were considered for inclusion in this study. Tapered implants featuring a nanostructured calcium-incorporated surface were placed and loaded immediately. The prosthetic restorations comprised single crowns, fixed partial dentures, and fixed full arches. Primary outcomes were implant survival, stability, and complications. Implant stability was assessed at placement and at each follow-up evaluation (1 week, 3 months, and 1 year after placement): implants with an insertion torque (IT) <45 N.cm and/or with an implant stability quotient (ISQ) <70 were considered failed for immediate loading. A statistical analysis was performed. RESULTS: Thirty implants were placed in postextraction sockets of 17 patients, and 32 implants were placed in healed sites of 22 patients. There were no statistically significant differences in ISQ values between the 2 groups, at each assessment. In total, 60 implants (96.8%) had an IT >=45 and an ISQ >=70 at placement and at each follow-up control: all these implants were successfully loaded. Only 2 implants (1 in a postextraction socket and 1 in a healed site, 3.2%) could not achieve an IT >=45 N.cm and/or an ISQ >=70 at placement or over time: accordingly, these were considered failed for stability, as they could not be subjected to immediate loading. One of these 2 implants, in a healed site of a posterior maxilla, had to be removed, yielding an overall 1-year implant survival rate of 98.4%. No complications were reported. No significant differences were reported between the 2 groups with respect to implant failures and complications. CONCLUSION: Immediately loaded implants placed in postextraction sockets and healed sites had similar high survival and stability, with no reported complications. Further long term studies on larger samples of patients are needed to confirm these results. PMID- 27391494 TI - The Phenotypes of Spheno-Occipital Synchondrosis in Patients With Crouzon Syndrome. AB - OBJECTIVE: To characterize the phenotypes of spheno-occipital synchondrosis (SOS) in Chinese patients with Crouzon syndrome. METHODS: Twelve patients with Crouzon syndrome were included in this retrospective study, and were divided into 2 groups. The first group included 5 patients (5-7-year old), whereas 7 patients were included in the second group (8-11-year old). Two age- and sex-matched control groups were constituted for comparison. All patients and controls were underwent preoperative computed tomography examinations of the craniofacial area, and the three-dimensional skull models, sagittal, and axial images were reconstructed. The density of the SOS region was also calculated. RESULTS: The SOS was partially closed in the first Crouzon patients group, whereas the SOS was open in control groups. The SOS was completely fused SOS in the second Crouzon patients group, whereas the SOS was open or partially closed in control groups. There also were short and hypoplastic sphenoid bone in both Crouzon groups when compared with controls. In addition, the average density of SOS in patients with Crouzon syndrome was higher than the control groups (P <0.01). CONCLUSIONS: The SOS begins to prematurely fuse in Chinese patients with Crouzon syndrome, and there are short and hypoplastic sphenoid bone in these patients. Although a definitive role of prematurely fused SOS in Crouzon syndrome cannot be drawn, our finds provide important clues into the mechanisms, and potentially provide a treatment target for midfacial and cranial vault hypoplasia in Crouzon patients. PMID- 27391495 TI - Maxillary Protraction With Intermaxillary Elastics to Miniplates Versus Bone Anchored Face-Mask Therapy in Cleft Lip and Palate Patients. AB - INTRODUCTION: Cleft lip and palate patients usually have deficient maxilla due to postsurgical scars. The aim this study was to compare the effectiveness of miniplates-anchored face-mask therapy versus intermaxillary elastics to miniplates for maxillary traction in cleft lip and palate patients. METHODS: This clinical trial included 11 prepubertal patients with cleft lip and palate. Initially, a w-arch expander was cemented and activated 3 mm per month to overcorrect the crossbite. Then, the patients were divided into 2 groups: mini plate-anchored face-mask (n = 5): 2 miniplates were placed in the maxilla and the patients were instructed to wear a face-mask for 12 to 14 hours/per day. Intermaxillary elastics to miniplates (n = 6): 2 miniplates were inserted in the maxilla; 1 on each side and 2 miniplates were placed in the anterior mandible on both sides. Intermaxillary elastics with a force of 250 g per side were attached to the hooks. Cephalometric parameters before treatment (T1) and after achieving positive overjet (T2) were compared between the 2 groups. Fisher exact, paired, and independent t tests were used for statistical comparison. RESULTS: At T1 or T2 there was not a significant difference between the 2 groups in the skeletal, dental, and soft tissue variables. CONCLUSION: According to results of our preliminary study, intermaxillary elastics to miniplates might have a promising effect as an alternative for face mask therapy in maxillary protraction of cleft lip and palate patients. PMID- 27391496 TI - Gardner Syndrome With Unusual Maxillofacial Manifestation. AB - Gardner syndrome is a rare autosomal-dominant condition characterized by the presence of intestinal polyposis, multiple osteomas, and tumors of the hard and soft tissues. This paper describes a patient of Gardner syndrome with unusual maxillofacial manifestation with presence of fibromyxomatous injury in jaw, coronoid hyperplasia, and multiple osteomas diffusely distributed in the craniomaxillofacial skeleton. Imaging examinations have identified craniofacial manifestations and the patient was referred to the gastroenterologist who confirmed the diagnosis of Gardner syndrome. The early diagnosis of this syndrome is important since intestinal polyps have high potential for malignant transformation. It is therefore essential that dentists are familiar with the maxillofacial features of this condition, since they precede the intestinal polyposis and encourage early diagnosis. In addition to classic maxillofacial signs of this syndrome, one must consider that, although it is rare, other injuries may be present such as those described in this clinical patient. PMID- 27391497 TI - Keystone Perforator Island Flap as an Alternative Reconstructive Option for Partial Thickness Alar Defects Up to 1.5 Centimeters. AB - INTRODUCTION: The ala is a unique landmark of the nose disposing aesthetic and functional properties. The head and neck area is the main site of appearance of nonmelanoma skin cancer. One third of them are located in the nose with an alar preponderance compared with other nasal subunits. Correction of alar defects is a challenging reconstructive task. The keystone perforator island flap (KPIF) was introduced as an alternative in nasal reconstruction by senior authors. In the present case series, KPIFs' application is introduced into the alar subunit as an alternative, versatile, and reproducible reconstructive option, even for the novice plastic surgeon. MATERIALS AND METHODS: From April 2014 to September 2015, patients presenting with partial thickness alar defects (<=1.5 cm) secondary to tumor extirpation sustained reconstruction with different types of KPIF. RESULTS: A total of 31 patients (mean age of 72 years) were treated with various types of KPIF. The mean diameter of the defect was 1.14 cm. The vast majority of reconstructions concerned a type IV KPIF (18/31 or 58.1%). Sometimes an upward alar retraction was noted. A minimal rim wedge excision was performed (<=0.3 mm) using counterbalancing correcting sutures. All flaps survived without any sign of venous congestion, whereas the rim healed uneventfully. The mean follow-up period was 6.5 months. CONCLUSIONS: KPIF was introduced as a single-stage alternative reconstructive option for partial thickness alar defects, completing author's experience with this flap into such a challenging and aesthetically critical anatomic area. PMID- 27391498 TI - Relationship Between Oral Perception and Habitual Chewing Side for Bare Bone Graft With Dental Implants After Mandibular Reconstruction. AB - OBJECTIVE: The purpose of this study was to investigate the relationship between habitual chewing side and perception of the oral mucosa following reconstruction with dental implants. STUDY DESIGN: Five patients comprised 2 males and 3 females, with ameloblastoma in 2 patients, odontogenic myxoma in 2 patients, and oral squamous cell carcinoma in 1 patient. They were treated using mandibular reconstruction with bare bone graft after segmental resection of the mandible. Perception (tactile, warm, and cold) was measured at 8 points (chin, lower lip, gingiva, and lateral edge of the tongue, bilaterally). Habitual chewing side was evaluated using a computerized index, the first chewing cycle, and a question on chewing. RESULTS: Perception on resected sides was improved at all measurement points for tactile and cold sensitive evaluation, although sensitivities on the resected side remained below the normal range. In the relationship between habitual chewing side and implanted prostheses in reconstructed bone, the chewing side was the resected side in 2 of the 5 patients. When those 2 patients underwent prosthesis implantation after removal of denture, the chewing side changed from the nonresected side to the resected side. Implant prostheses on resected side were suggested to contribute to masticatory function. Perception in those patients was incomplete but was improved compared with other patients. When prosthesis implantation is performed on the reconstructed side, the resected side may become the habitual chewing side. CONCLUSIONS: Recovery of perception can influence acquisition of the habitual chewing side. PMID- 27391499 TI - The Management of Iatrogenic Obstructive Sleep Apnoea Syndrome Following Bimaxillary Surgery in a Patient with Cleft Lip and Palate. AB - A 26-year-old man presented with a 6-year history of severe obstructive sleep apnoea syndrome followed a bimaxillary osteotomy procedure for a class III skeletal pattern. The patient was born with a unilateral cleft lip and palate and underwent primary lip and palate repair and later a pharyngeal flap for severe velopharyngeal insufficiency. Surgical management of obstructive sleep apnoea syndrome with conventional osteotomy, in cleft lip and palate patients, is a difficult problem. Distraction osteogenesis may provide a safer alternative. The authors describe and discuss the indications and the technical challenge of a multistage treatment protocol with distraction osteogenesis. PMID- 27391500 TI - Evaluation of Patient Satisfaction After Nasal Septoplasty Operation Using Peak Nasal Inspratuar Flow and Nasal Obstruction Symptom Score Questionare. AB - BACKGROUND: The purpose of this study was to investigate the usefulness of the peak nasal inflamatuar flow (PNIF) and Nasal Obstruction Symptom Score (NOSE) questionnaire in the diagnosis and follow-up of nasal septum deviation surgery. METHODS: Sixty patients diagnosed with nasal septum deviation were included in the study. Nasal Obstruction Symptom Score scales of patients, PNIF and is measured preoperatively and 14 days after surgery. RESULTS: Preoperative NOSE scores were 14.9 +/- 2.7 and PNIF scores were 129.6 +/- 15.5 L/min in study group. Postoperatively NOSE scores were 7.9 +/- 1.8 and PNIF scores were 154.2 +/ 9.2 L/min in study group. Nasal Obstruction Symptom Score scores were 3.3 +/- 2.3 and PNIF scores were 169.3 +/- 13.5 L/min in control group. CONCLUSION: Anterior and anteroposteriorly located nasal septum deviation (NSD) had statistically higher degrees of NOSE scores and lower levels of PNIF scores. Posterior located NSD PNIF scores changed postoperatively but NOSE scores do not change statistically. There was a statistically significant correlation in Pearson correlation analysis between NOSE and PNIF scores. The authors recommend using PNIF and NOSE scores in NSD patients. PMID- 27391501 TI - Evaluation of Optic Canal and Surrounding Structures Using Cone Beam Computed Tomography: Considerations for Maxillofacial Surgery. AB - The optic canal connects the anterior cranial fossa and the orbit and maintains the optic nerve and the ophthalmic artery. Within the extent of the surgical approach of the region, risk of iatrogenic injury of the neural and vascular structures increases. The aim of this retrospective morphometric study is to investigate the radiological anatomy of orbita, optic canal, and its surrounding using cone beam computed tomography (CBCT) scans in a group of Turkish population.Cone beam computed tomography images of a total of 182 patients were evaluated by 2 observers. Anatomical parameters regarding optic canal and orbita were measured for all patients from axial, sagittal, and three-dimensional reconstructed images. To assess intraobserver reliability, the Wilcoxon matched pairs test was used. Pearson chi test and Student t test were performed for statistical analysis of differences, sex, localization, and measurements (P < 0.05).Repeated CBCT evaluation and measurements indicated no significant inter and intra-observer difference were found (P > 0.05). The orbita width and height were larger for the males than females (P < 0.05). No significant difference was observed for optic canal shape, dimensions of infraorbital foramen (IOF) and supraorbital foramen (SOF), SOF-midline distance, and SOF-IOF distance according to sex and location (P > 0.05). Examination CBCT scans revealed that the shape of the optic canal was 70% funnel and 28% Hourglass shape, 2% amorph type round.These results provide detailed knowledge of the anatomical characteristics in the orbital area which may be of assistance for surgeons preoperatively. Cone beam computed tomography scans can be an alternative modality for multislice computed tomography with submillimeter resolution and lower dose in preoperative imaging of the orbit. PMID- 27391502 TI - Anatomic Variations in Paranasal Sinuses of Patients With Sinonasal Polyposis: Radiological Evaluation. AB - OBJECTIVE: Although sinonasal anatomic variations have been postulated as a risk factor for sinus disease, the role of anatomic abnormalities in the pathogenesis of nasal polyps is still unclear. This study was conducted to examine the association of sinonasal polyposis with anatomic variations. METHODS: The paranasal sinus computerized tomography scans of 155 patients with sinonasal polyposis were examined retrospectively from January 2012 to 2014 in a tertiary care hospital. Paranasal sinus computerized tomography of 100 patients without complaints and signs of sinus disease were also included to serve as control group. The incidence of anatomic variations was evaluated. The sinonasal polyposis and control group data was compared statistically. RESULTS: The incidence of the septal deviation, concha bullosa, Agger nasi, frontal sinus hypoplasiaand accessory sinus ostium in healthy subjects, and sinonasal polyposis patients revealed statistically significant difference. The mentioned variations were found significantly higher in sinonasal polyposis patients (P = 0.000, P = 0.000, P = 0.001, P = 0.002, and P = 0.035 respectively) and may be predisposing for this pathology. CONCLUSION: Considering the results obtained, the presence of septal deviation, concha bullosa, Agger nasi cell, frontal sinus hypoplasiaand accessory sinus ostium may play role in pathogenesis of sinonasal polyposis. PMID- 27391503 TI - Relationship Between Age and Diagnosis on Volumetric and Linear Velopharyngeal Measures in the Cleft and Noncleft Populations. AB - The purpose of this study was to create a 3D volumetric segmentation from magnetic resonance imaging (MRI) of the nasopharyngeal space and adenoid tissue and to examine the relationship between nasopharyngeal volume (NPV), adenoid volume, and linear measures of the velopharyngeal structures, pharynx, and vocal tract in children with and without cleft palate. A total of 24 participants including 18 typically developing children (4-8 years of age) and 6 children (4-8 years of age) with varying degrees of cleft palate were imaged using MRI. Linear and volumetric variables varied significantly based on age. Overall, NPV demonstrates a modest increase with age. Nasopharyngeal volume was positively correlated with age (P = 0.000), oronasopharyngeal volume (P = 0.000), velar length (P = 0.018), and velar thickness (P = 0.046). These variables tend to increase together. Differences in NPV between groups (bilateral cleft lip and palate, submucous cleft lip and palate, unilateral cleft lip and palate [UCLP], and noncleft) were statistically significant (P = 0.007). Participants with bilateral cleft lip and palate demonstrated greater NPVs than those with UCLP and submucous cleft palate. PMID- 27391505 TI - Castleman Disease of Parotid Gland. PMID- 27391504 TI - The Clinical Features and Expression of bcl-2, Cyclin D1, p53, and Proliferating Cell Nuclear Antigen in Syndromic and Nonsyndromic Keratocystic Odontogenic Tumor. AB - The aim of this study was to describe the clinical features and expression of bcl 2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT). METHODS: This descriptive study comprised 5 patients of KCOT associated with NBCCS and 8 patients of nonsyndromic type treated in the Department of Oral Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre between years 1998 and 2011. The clinical features (site, size, treatment, and recurrence), demographic characteristics, and immunohistochemistry results using antibodies of bcl-2, cyclin D1, p53, and PCNA were examined. The association of the antibody expression and the type of KCOT was analyzed using Fisher exact test. RESULTS: Altogether there were 13 patients, 5 with syndromic KCOT (1 patient met 3 major criteria of NBCCS) and 8 with sporadic KCOT. The age range for syndromic KCT was 11 to 21 years (mean 16.00 years, SD 4.36) and 10 to 54 years (median 24.50 years, interquartile range 19.00) for the nonsyndromic KCOT. Tumor recurrence occurred in 3 patients (7.7%); 1 patient from the syndromic and 2 patients from the nonsyndromic. The most positive expression was observed in PCNA for both the syndromic and nonsyndromic samples and the least positive expression involved the p53. CONCLUSION: PCNA, bcl-2 protein, and cyclin D1 expressions could be useful in evaluating the proliferative activity of the tumor and the aggressiveness of the clinical presentation; however, the authors would propose for larger sample size research for more definitive results. PMID- 27391506 TI - Upper Lip Reconstruction. PMID- 27391507 TI - Congenital Fistula of the Hard Palate With Submucosal Cleft Palate. PMID- 27391508 TI - Fibrosis Within the Tympanic Membrane. AB - A primary mass lesion arising from the tympanic membrane is extremely rare. The authors report a patient of extensive fibrosis within the tympanic membrane in a 65-year-old woman who did not have a history of ear infection. The patient complained of slow progressing hearing loss on the left side without otorrhea or otalgia. Otoscopic examination showed a thick tympanic membrane with whitish mass like bulge, and pure-tone audiometry revealed conductive hearing loss. The lesion was totally resected, and final findings of a histopathologic examination revealed extensive fibrosis with subsiding inflammation within the tympanic membrane. Fibrosis within the tympanic membrane may present with slow progressing conductive hearing loss and should be considered a possible differential diagnosis of mass lesions in the tympanic membrane. PMID- 27391509 TI - Rehabilitation of Patient of Glass Cut Injury With Forehead Flap Repositioning and Implant-Retained Nasal Prosthesis. AB - Traumatic injuries, especially in maxillofacial region, not only lead to physical debilitation but also cause severe psychological distress in the affected individuals. Complete cosmetic and functional rehabilitation of such patients is a challenging task and thus requires a strategic treatment planning and a multidisciplinary team to execute the treatment. This patient report presents a patient who suffered with a severe glass cut injury leading to massive avulsion of face involving forehead, nose, upper lip, and anterior teeth. Patient was rehabilitated with a combined surgical and prosthetic approach, which involved flap repositioning in forehead, nasal and lip regions and an implant-supported nasal prosthesis to replace missing nose. Missing anterior teeth were replaced with fixed dental prostheses. PMID- 27391510 TI - Treatment Options in Maxillofacial Fractures. AB - From 2000 to 2010, 720 patients with facial trauma were admitted in Plastic Surgery Service of Argerich Hospital, Buenos Aires, Argentina; 58 of them with panfacial fractures were included in this study. Height velocity impact is the principal etiology, and most concomitant extrafacial injuries are neurocranium and cervical spine. Common affected areas were orbits, nose, and malar-zygoma. The timing of the treatment was airway evaluation, control of bleeding and consciousness, treatment of associated injuries, and finally facial reconstruction. The applications of craniofacial surgical techniques complete facial treatment in only operatory time by means of standard approaches like coronal, subciliar palpebral, upper and lower vestibular. The treatment was exploration to open sky; reduction and fijation with titanium plates; replacement of comminuted bones with bone autografts harvested iliac crest, calvary, and costal bones. The results were classificated acceptables in 48 (85%) and not acceptables in 9 (15%) according to successful reconstruction of the both form and armony facial, persistent esthetic and functional sequels, and postoperative complications. Postoperative complications were detected in 18 patients. According to most authors the use of internal rigid fixation and bone autograf permits obtaining the best aesthetic and functional results decreasing complications and sequels. The recuperation of tridimensional aspect of the face and aesthetic and functional pretrauma state must be the goal standard. PMID- 27391511 TI - Resection of Giant Hemangioma of the Tongue Utilizing a Miniature Tourniquet Technique. AB - With the progress of multidisciplinary vascular anomaly treatment, the use of radiotherapy, cryotherapy, laser therapy and medical treatments, the corticosteroid, sclerotherapy, and many more, the role of surgery has been refined. Surgical treatment has historically been the mainstay of treatment and will maintain.A miniature tourniquet technique applied to the tongue was successfully utilized in reducing bleeding to a minimum during surgical resection of a massive cavernous hemangioma involving the tongue and lower lip without any postoperative complications.Comprehensions of the neurovascular anatomy of the tongue, vasculature, innervations, and muscles physiological functions are very important for selecting the right surgical approach.A 9-year-old girl presented with giant hemangioma resulting in severe protrusions of the anterior and lateral two-thirds of the tongue with an extensive anterior open bite jaw deformity and oral physiological dysfunctions as speech, mastication, and deglutition. Such a presentation is a unique surgical challenge due to the high risk of bleeding, tongue swelling, and airway compromise.Postsurgical results showed oral physiological function improvement and the elimination of interaction effects on anterior open bite. PMID- 27391512 TI - Actinomycotic Osteomyelitis of Mandible. AB - Actinomycosis is an infection of filamentous, gram-positive anaerobic bacteria. Actinomycosis of jaw bone is rare and the diagnosis is often difficult. The aim of this patient report is to present an actinomycotic osteomyelitis of mandible in a 30-year-old male patient. The patient presented with a chief complaint of pain and unhealed dental socket after mandibular teeth extractions. Radiographs showed ill-defined radiolucencies and perforation of buccal and lingual cortical plate; several biopsies and different therapy could not improve the lesion because of fault diagnosis and improper treatment. Finally, the authors' histopathological examination revealed granulation tissue surrounded bacterial colonies compatible with actinomycotic colonies. Follow-up examinations showed that the patient was well 6 months after prolonged treatment without any pain and discharge from dental socket. PMID- 27391513 TI - Lateral Orbital Wall Destruction Due to Pilonidal Sinus. AB - Pilonidal sinus is a chronic inflammatory disease commonly observed in the sacrococcygeal region. The authors report a patient of a pilonidal sinus in a rare location-the lateral orbital region. The authors' patient was misdiagnosed with an epidermal cyst, and the subsequent incomplete excision of the sinus tract led a pilonidal sinus with a high morbidity resulting in the destruction of bone tissue in the lateral orbital wall. It was, therefore, crucial to accurately diagnose and treat before the infection progressed through the bone and caused osteomyelitis. PMID- 27391514 TI - Obliteration of Recurrent Large Dentigerous Cyst Using Bilateral Buccal Fat Pad Sling Flaps. AB - Dentigerous cyst (DC), also known as follicular cyst, is an odontogenic cyst with fluid accumulation between the crown and enamel organ of an unerupted tooth, pushing the crown away from the alveolar bone. The patients with DC in the maxillary sinus should be evaluated thoroughly by extraoral and intraoral examinations, proper diagnostic imaging procedures, and pathologic examination to avoid misdiagnosis of maxillary sinusitis. The standard treatment for DC in the maxillary sinus is often removed by Caldwell-Luc approach. Furthermore, marsupialization or functional endoscopic sinus surgery may be performed because of the size, location of the cysts, or the age of the patients. Sometimes, DC recurred and it made contour deformity. The buccal fat pad (BFP) was mentioned for the first time by Heister in 1732 and better described by Bichat in 1802. Egyedi was the first to report use of the BFP in oral reconstruction for the closure of oroantral and oronasal communications, and Tideman et al showed there was no need to cover BFP by a skin graft when used for defects of oral cavity. So, the authors report our experience with the bilateral pedicled sling BFP flap for intraoral reconstruction after larger recurrent DC removal and describe advantages, operative procedure, and possible complications of the DC. PMID- 27391515 TI - Comparison of Frey Syndrome Rates Following Superficial Parotidectomy and Partial Superficial Parotidectomy for Pleomorphic Adenoma. AB - PURPOSE: Comparison of Frey syndrome rates following superficial parotidectomy and partial superficial parotidectomy for pleomorphic adenoma. METHODS: Fifty patients diagnosed with pleomorphic adenoma and received surgical treatment at the Otolaryngology Department of Bagcilar Training and Research Hospital between January 2009 and October 2015 were reviewed retrospectively. The patients were specifically queried for Frey syndrome symptoms. The syndrome was investigated with Minor starch iodine test. The patients who underwent superficial parotidectomy were compared to those who underwent partial superficial parotidectomy in terms of Frey syndrome development and recurrence. RESULTS: In the partial superficial parotidectomy group, Frey syndrome symptoms were edema and increased sweating and burning sensation on the face in 7 patients (21.9%, P = 0.735). In the superficial parotidectomy group, 5 patients exhibited edema (27.8%), 3 exhibited increased sweating (16.7%), and 5 exhibited burning sensation (27.8%). Minor test results were positive for 7 patients in the partial superficial parotidectomy group (21.8%) and 5 patients were positive (27.8%) in the superficial parotidectomy group. No recurrence was found in either group during the 5-year follow-up. No significant difference was found between 2 groups in terms of postoperative complications and recurrence. CONCLUSION: In terms of their effect on Frey syndrome development, there is no significant difference between partial superficial parotidectomy and superficial parotidectomy. PMID- 27391516 TI - Surgical Treatment of Class III Malocclusion: Monozygotic Twin. AB - Mandibular deformities present with infinite variation with different aesthetic and functional problems. Orthognathic surgery is required to achieve satisfactory results for functional and aesthetically in mandibular prognathism patient. Setback of the mandible to correct mandibular prognathism is a well-known procedure. The 2 most frequently used techniques are the intraoral vertical ramus osteotomy and the bilateral sagittal split ramus osteotomy (BSSRO). Bilateral sagittal split ramus osteotomy is an effective and commonly used method to correct mandibular prognathism. In this patient report, mandibular prognathism in female monozygotic twin patients was treated with BSSRO is presented. PMID- 27391517 TI - The Freestyle Facial Artery Perforator Flap for Reconstruction of Simultaneous Periorbital and Cheek Defects. AB - The reconstruction of defects involving the nasolabial, paranasal, and periorbital regions may be challenging, because they often involve more than one facial aesthetic unit, and can lead to functional problems. An average of 5 facial artery perforators of caliber >0.5 mm can be found above the mandible. A reference point for the location of the most constantly encountered perforator was suggested as being 1.5 cm lateral to the oral commissure, and at its same level in height or slightly inferior to the commissure. Based on injection studies, it is known that these perforators can supply an average area of 8 cm. The authors have extended the use of the freestyle perforator flap in a 87-year old woman presented with an advanced melanoma of the paranasal area and nasolabial region (Breslow depth: 9 mm; Clark level V). Complete resection of the lesion with 3 cm oncological margins was performed. One-stage reconstruction with superior cosmetic results was achieved. The need for a perforator dissection is not necessarily a drawback, and classic concerns should be abandoned. The face is highly vascularized, and flap congestion is a rare event, usually a consequence of excessive pedicle trimming. Although technically more demanding, it should become one of the first reconstructive options when dealing with similar defects, if our results are confirmed in larger series. PMID- 27391518 TI - The Use of Topical Lidocaine Gel During Intermaxillary Fixation Procedure. AB - This study aimed to validate the usefulness of lidocaine gel during intermaxillary fixation using arch bars in patients with mandible fracture by comparing 2 patient groups: one group using lidocaine gel in intermaxillary fixation and the other group undergoing traditional local infiltration.Subjects were patients with mandible fracture undergoing intermaxillary fixation using arch bars from March 2003 to February 2007. Twenty-three patients were anesthetized in the upper and lower gingiva by 2% local lidocaine solution injection; another 23 underwent topical anesthesia with 2% lidocaine hydrochloride gel applied to the upper and lower gingiva. The convenience of fixation was measured in terms of operation time and degree of pain according to the visual analog scale; arch bar loosening rate was assessed postoperatively.The mean operation times were 63 and 47 minutes in the groups undergoing local infiltration and using topical lidocaine gel, respectively. For pain degree according to the visual analog scale, the mean scores were 6.4 and 3.2 in the groups using local infiltration and topical lidocaine gel, respectively. When the arch bar loosening rate was measured postoperatively, the 2 groups differed significantly, with a rate of 26% in the group using local infiltration and 13% in the group using topical lidocaine gel.Application of topical lidocaine gel during intermaxillary fixation using arch bars in patients with mandible fracture relieves pain and offers convenience in performing the procedure. It can be a useful alternative method for patients who are sensitive to pain or have needle phobia. PMID- 27391519 TI - The Effects of Nasal Packing and Transseptal Suturing After Septoplasty on Olfactory Function, Patient Comfort, and Mucociliary Clearance. AB - BACKGROUND: This study compared the effects of nasal packing and transseptal suturing after septoplasty by evaluating olfactory function, pain, and mucociliary clearance. METHODS: The study enrolled 39 patients diagnosed with isolated septal deviation. The patients were randomly assigned to 2 groups. In Group A (n = 21), transseptal sutures were placed for septal stabilization after the septoplasty. In Group B (n = 18), both nasal passages were packed with Merocel tampons after the septoplasty. It was made Sniffin Sticks test, sacchranirine test, and pain and discomfort scales preoperatively, 1 week postoperatively and 3 months postoperatively on all patients. RESULTS: There was no postoperative bleeding, submucoperichondrial haematoma, or abscess formation in either group. The postoperative discomfort and pain scores were increased in Group B (the packing group) in our study, the mucociliary clearance improved after septoplasty in both groups, and there was no significant difference in mucociliary clearance between the 2 groups. The odor threshold, odor identification, and odor discrimination were significantly increased 3 months postoperatively, but not 1 week postoperatively. CONCLUSIONS: Nasal packing causes more discomfort and pain than transseptal suturing, while there was no significant difference in olfactory functions or the mucociliary clearance after septoplasty between nasal packing and transseptal suturing. PMID- 27391520 TI - Recurrent Keratocystic Odontogenic Tumor After Effective Decompression. AB - Keratocystic odontogenic tumor (KCOT) has potential aggressive and infiltrative behavior. Decompression has been widely preferred for large KCOTs due to safety and lower recurrence rates. However, KCOT is still likely to recur even after effective decompression. Here, we present a rare and interesting case of recurrent KCOT after effective decompression with adjunctive enucleation. Redecompression was then performed again, and the effect was still satisfactory on long-term follow-up. PMID- 27391521 TI - Is Delayed Release of Superior Oblique Muscle Entrapment in Orbital Roof Fracture Worth Correcting? AB - Acquired Brown's syndrome is a rare entity. Delay in treatment can cause fibrosis or scarring with questionable prognosis of vertical diplopia. To the best of the knowledge of the authors the present case of 22-year-old male is the first in existing literature where delayed release of superior oblique muscle entrapment in orbital roof fracture was found to be an effective technique. PMID- 27391522 TI - Evaluation of Mandibular Anatomy Associated With Bad Splits in Sagittal Split Ramus Osteotomy of Mandible. AB - PURPOSE: This study aimed to identify risk factors associated with bad splits during sagittal split ramus osteotomy by using three-dimensional computed tomography. METHODS: This study included 8 bad splits and 47 normal patients without bad splits. Mandibular anatomic parameters related to osteotomy line were measured. These included anteroposterior width of the ramus at level of lingula, distance between external oblique ridge and lingula, distance between sigmoid notch and inferior border of mandible, mandibular angle, distance between inferior outer surface of mandibular canal and inferior border of mandible under distal root of second molar (MCEM), buccolingual thickness of the ramus at level of lingula, and buccolingual thickness of the area just distal to first molar (BTM1) and second molar (BTM2). RESULTS: The incidence of bad splits in 625 sagittal split osteotomies was 1.28%. Compared with normal group, bad split group exhibited significantly thinner BTM2 and shorter sigmoid notch and inferior border of mandible (P <0.05). However, for BTM1 and buccolingual thickness of the ramus at level of lingula, there was no statistical difference between the 2 groups. Mandibular angle, anteroposterior width of the ramus at level of lingula, external oblique ridge and lingula, and MCEM were not significantly different between the groups. CONCLUSION: This study suggests that patients with shorter ramus and low thickness of the buccolingual alveolar region distal to the second molar had a higher risk of bad splits. These anatomic data may help surgeons to choose the safest surgical techniques and best osteotomy sites. PMID- 27391523 TI - Aspergillus Osteomyelitis of the Skull. AB - Osteomyelitis of the craniofacial skeleton is rare, with fungal pathogens least commonly implicated. The authors present 2 patients of osteomyelitis of the skull caused by Aspergillus spp. and discuss the diagnosis, clinicopathological course, and management strategies.Late recurrence seen in this type of infection warrants long-term follow-up and a high index of suspicion for the clinical signs associated with recurrence.Such patients would benefit from their surgical debridement being planned and managed via a specialist craniofacial unit, so as to utilize the most aesthetically sensitive approach and the experience of specialists from several surgical disciplines. PMID- 27391524 TI - A New Radiologic Protocol and a New Occlusal Radiographic Index for Computer Guided Implant Surgery. AB - A minimum interarch space of 40 mm along the planned direction of the implant is physically mandatory to allow computer-guided implant placement with the NobelGuide technique. The aim of this paper was to describe a novel radiologic protocol and a new occlusal radiographic index that give the clinician the possibility of identifying patients with limited interarch space. Three patients undergoing NobelGuide treatment of the edentulous upper jaw were selected as candidates for this study. In the first patient, the radiographic occlusal index was built using an addition silicone material to occupy the space between the 2 arches forced into the maximum opening position. In the other 2 patients different silicone materials were used and 2 interpositional wedges were placed in between 2 silicone bites to ensure maximum mouth opening. In the first patient, the bite made with addition silicone alone resulted in distinct noise on computer tomography since the patient was not forced to achieve his maximum opening position. In the second patient the mandibular addition silicone was still quite visible, while in the third patient the condensation silicone was invisible and the quality of the image was excellent with the possibility of measuring maximum opening position and virtually predicting interference with the opposite arch. The new radiological occlusal index made with condensation silicone (Sandwich Index) proved to be effective in reproducing the maxillary forced maximum opening position during the initial planning phase, preventing errors in the inclusion or exclusion of patients suitable for NobelGuide treatment. PMID- 27391525 TI - Cooperative Self-Assembly of Carbazole Derivatives Driven by Multiple Dipole Dipole Interactions. AB - Carbazole possessing phenylisoxazoles self-assembled in a cooperative manner in decalin. X-ray crystal structure analysis revealed that the isoxazole dipoles align in a head-to-tail fashion. DFT calculations suggested that the linear array of dipoles induced the polarization of each dipole, leading to an increase in dipole-dipole interactions. This dipole polarization resulted in cooperative assembly. PMID- 27391526 TI - Influence of spatial and temporal coherences on atomic resolution high angle annular dark field imaging. AB - Aberration-corrected (scanning) transmission electron microscopy ((S)TEM) has become a widely used technique when information on the chemical composition is sought on an atomic scale. To extract the desired information, complementary simulations of the scattering process are inevitable. Often the partial spatial and temporal coherences are neglected in the simulations, although they can have a huge influence on the high resolution images. With the example of binary gallium phosphide (GaP) we elucidate the influence of the source size and shape as well as the chromatic aberration on the high angle annular dark field (HAADF) intensity. We achieve a very good quantitative agreement between the frozen phonon simulation and experiment for different sample thicknesses when a Lorentzian source distribution is assumed and the effect of the chromatic aberration is considered. Additionally the influence of amorphous layers introduced by the preparation of the TEM samples is discussed. Taking into account these parameters, the intensity in the whole unit cell of GaP, i.e. at the positions of the different atomic columns and in the region between them, is described correctly. With the knowledge of the decisive parameters, the determination of the chemical composition of more complex, multinary materials becomes feasible. PMID- 27391527 TI - Low Threshold Two-Photon-Pumped Amplified Spontaneous Emission in CH3NH3PbBr3 Microdisks. AB - Two-photon-pumped amplified spontaneous emission (ASE) of CH3NH3PbBr3 microdisks (MDs) were investigated by using femtosecond laser system. Low threshold at 2.2 mJ cm(-2) was obtained. Also, emission spectral tunability from 500 to 570 nm was demonstrated by synthesis the mixed halide perovskite MDs. The spatial effect of photoluminescence (PL) properties under one-photon and two-photon excitation were also studied by means of two-photon laser scanning microscope (TPLSM) and time resolved PL spectroscopy. It was found that the band to band emission of near surface regions and photocarriers' diffusion from near-surface regions to interior regions is significant for one-photon excitation. By contrast, reabsorption of emission under two-photon excitation plays a major role in the emission properties of the MDs. These results will give a more comprehensive understanding of the nonlinear effect of CH3NH3PbBr3 single crystals. PMID- 27391528 TI - The Experience of Men Caring for a Partner With Multiple Sclerosis. AB - PURPOSE: The aim of this study was exploring the experience of male caregivers living with a partner with multiple sclerosis (MS). DESIGN AND METHODS: A qualitative study was conducted following a grounded theory approach. Twenty-four men-husbands or partners of a woman diagnosed with MS-were interviewed in-depth. A thematic analysis was carried out and involved line-by-line coding with codes deriving from narratives. FINDINGS: Five major themes emerged: caregiving as a full-time job; changes in the couple; the importance of social support and social life; gender specificities; and fear of the future. CONCLUSIONS: Results highlight the complexity of issues surrounding this specific form of caregiving. Social expectations referring to the marital relationship and to gender norms play a central role. CLINICAL RELEVANCE: Findings can help in developing ad hoc interventions to support male spousal caregivers to care for their partners. PMID- 27391529 TI - The mu (MU) and delta (delta) opioid receptors modulate boar sperm motility. AB - Endogenous and exogenous opioids modulate reproductive functions in target cells via opioid receptors (MU, delta, and kappa). Sperm motility is a metric of gamete functionality, and serves as a suitable parameter for in vitro drug-induced toxicity assays. This study identifies the presence and location of opioid receptors in pig spermatozoa as well as their functional response after in vitro challenge with known agonists (morphine [MU]; [D-Pen 2,5]-enkephanile [delta]; and U 50488 [kappa]) and antagonists (naloxone [MU]; naltrindole [delta]; and nor binaltrorphimine [kappa]). Only the MU- and delta-opioid receptors were present in the boar sperm plasma membrane, overlying the acrosome, neck, and principal piece. Challenge experiments with agonists and antagonists identified both MU- and delta-opioid receptors as regulators of sperm kinematics, wherein MU maintains or increases sperm movement whereas delta decreases sperm motility over time. Mol. Reprod. Dev. 83: 724-734, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27391530 TI - Near Point of Convergence after Concussion in Children. AB - PURPOSE: To determine the incidence of abnormal near point of convergence (NPC) after acute concussion in pediatric patients and to describe the clinical course of such patients. METHODS: A retrospective cohort study of 275 pediatric patients 5 to 18 years of age presenting to a tertiary care children's hospital subspecialty concussion program with a new concussion between July 1, 2014 and June 30, 2015 was conducted. RESULTS: Sixty-seven out of 275 pediatric patients presenting to a subspecialty concussion referral program were found to have abnormal NPC on physical examination as measured by an accommodative rule. Twenty six (46%) patients recovered with standard clinical care over a median time frame of 4.5 weeks (range 1-18), including a brief period of cognitive and physical rest followed by gradual return to school and physical activities without any formal interventions. An additional 23 (41%) patients recovered a median of 11 weeks post-injury after referral for formal vestibular therapy, including interventions for abnormal convergence, such as Brock string and pencil pushups. Seven (13%) patients with persistent abnormal NPC and concomitant symptoms that necessitated referral for formal office-based vision therapy with developmental optometry recovered a median of 23 weeks post-injury and a median of 16 weeks after referral to vision therapy. CONCLUSIONS: Assessment for NPC is a diagnostic entity that warrants consideration in children with concussion. Concussion questionnaires may not be sensitive to detect vision symptoms in children, making an accurate assessment for convergence important in the evaluation of concussion. Some children with abnormal NPC will recover without any formal intervention after concussion; however, a subset of patients with persistent abnormal NPC after concussion may benefit from interventions including vestibular and/or vision therapy. PMID- 27391531 TI - Pathology of the Superior Colliculus in Chronic Traumatic Encephalopathy. AB - PURPOSE: To investigate neuropathological changes in the superior colliculus in chronic traumatic encephalopathy. METHODS: The densities of the tau immunoreactive neurofibrillary tangles, neuropil threads, dot-like grains, astrocytic tangles, and neuritic plaques, together with abnormally enlarged neurons, typical neurons, vacuolation, and frequency of contacts with blood vessels, were studied across the superior colliculus from pia mater to the periaqueductal gray in eight chronic traumatic encephalopathy and six control cases. RESULTS: Tau-immunoreactive pathology was absent in the superior colliculus of controls but present in varying degrees in all chronic traumatic encephalopathy cases, significant densities of tau-immunoreactive neurofibrillary tangles, NT, or dot-like grains being present in three cases. No significant differences in overall density of the tau-immunoreactive neurofibrillary tangles, neuropil threads, dot-like grains, enlarged neurons, vacuoles, or contacts with blood vessels were observed in control and chronic traumatic encephalopathy cases, but chronic traumatic encephalopathy cases had significantly lower mean densities of neurons. The distribution of surviving neurons across the superior colliculus suggested greater neuronal loss in intermediate and lower laminae in chronic traumatic encephalopathy. Changes in density of the tau-immunoreactive pathology across the laminae were variable, but in six chronic traumatic encephalopathy cases, densities of tau-immunoreactive neurofibrillary tangles, neuropil threads, or dot-like grains were significantly greater in intermediate and lower laminae. Pathological changes were not correlated with the distribution of blood vessels. CONCLUSIONS: The data suggest significant pathology affecting the superior colliculus in a proportion of chronic traumatic encephalopathy cases with a laminar distribution which could compromise motor function rather than sensory analysis. PMID- 27391532 TI - Oculometric Assessment of Sensorimotor Impairment Associated with TBI. AB - PURPOSE: Diffuse tissue damage from impact or blast traumatic brain injury (TBI) degrades information processing throughout the brain, often resulting in impairments in sensorimotor function. We have developed an eye-movement assessment test, consisting of a simple, appropriately randomized, radial tracking task together with a broad set of oculometric measures that can be combined to yield a sensitive overall indicator of sensorimotor functional status. We show here that this multidimensional method can be used to detect and characterize sensorimotor deficits associated with TBI. METHODS: To compare dynamic visuomotor processing of TBI subjects (n = 34) with a separate control population (n = 41), we used the Comprehensive Oculometric Behavioral Response Assessment (COBRA) method (Liston & Stone, J Vision. 14:12, 2014) to quantify 10 performance metrics for each subject. Each TBI subject's set of oculometrics was then combined to compute a single TBI impairment vector whose magnitude we refer to as the impairment index. RESULTS: In our TBI population, several individual oculometrics were significantly degraded, including pursuit latency, initial pursuit acceleration, pursuit gain, catch-up saccade amplitude, proportion smooth tracking, and speed responsiveness. Furthermore, the TBI impairment index discriminated TBI subjects from controls with an 81% probability that increased with self-reported TBI severity; although the 9 subjects self-reporting "little to-no" residual impairment were statistically indistinguishable from controls (58% probability), the remaining 25 subjects were easily detectable (91% probability). Given the demonstrated link between higher-order visual perception/cognition and eye movements, we interpret the observed TBI-related impairments as degradations in the speed, accuracy, and precision of information processing within cortical circuits supporting higher-order visual processing and sensorimotor control, not just low-level brainstem motor deficits. CONCLUSIONS: We conclude that multidimensional oculometric testing could be used as a sensitive screen for subtle neurological signs of subclinical neurological insults, to quantify functional impairment, to monitor deterioration or recovery, and to evaluate treatment efficacy. PMID- 27391533 TI - Lid Wiper Epitheliopathy in Soft Contact Lens Wearers. AB - PURPOSE: To evaluate lid wiper epitheliopathy (LWE) in soft contact lens (SCL) wearers on initial presentation and after using various SCL and solution combinations. METHODS: LWE was assessed in 253 habitual SCL wearers who attended a screening visit at one of three study sites. LWE was assessed using lissamine green and sodium fluorescein dyes (Korb scale); a final LWE grade was calculated as the averaged LWE grade of the two dyes. Eligible habitual wearers continued into the four study periods, during which they wore one of three SCL types (etafilcon A, galyfilcon A, or senofilcon A) while using each of four care solutions for 10 to 14 days in randomized order. Statistical analyses were performed using linear mixed models, testing for differences in LWE for subject characteristics and between three multipurpose (MPS) test solutions (BioTrue, OPTI-FREE PureMoist, RevitaLens OcuTec) compared to a hydrogen peroxide (Clear Care) control solution. RESULTS: LWE was present in 85% of habitual SCL wearers. LWE was not different for age (p = 0.28), sex (p = 0.99), race (p = 0.34), and comfort (p = 0.38) and not correlated with refractive error (r = 0.07). LWE was lower in habitual senofilcon A wearers (least-squares (LS) mean +/- SE = 0.82 +/- 0.19) compared to wearers of lotrafilcon B (1.34 +/- 0.20; p < 0.02), comfilcon A (1.41 +/- 0.21; p < 0.01), and other (1.18 +/- 0.16; p < 0.03). Two hundred three participants completed all four study solutions with their assigned lens type; LWE was not different between the MPSs compared to the peroxide control solution across lens materials, except for less LWE for BioTrue (0.88 +/- 0.17) versus Clear Care for participants wearing galyfilcon A (1.11 +/- 0.18; p < 0.01). CONCLUSIONS: On initial presentation, LWE was present in 85% of habitual wearers and found to be independent of age, sex, race, comfort, and refractive error but dependent on habitual SCL type. There were no clinically meaningful differences in LWE between the MPSs and hydrogen peroxide solution for the three lens types studied. PMID- 27391534 TI - Visual Discrimination Increase by Yellow Filters in Retinitis Pigmentosa. AB - PURPOSE: The objective of this study was to evaluate, by halometry and under low illumination conditions, the effects of short-wavelength light absorbance filters on visual discrimination capacity in retinitis pigmentosa patients. METHODS: This was an observational, prospective, analytic, and transversal study on 109 eyes of 57 retinitis pigmentosa patients with visual acuity better than 1.25 logMAR. Visual disturbance index (VDI) was determined using the software Halo 1.0, with and without the interposition of filters which absorb (totally or partially) short-wavelength light between 380 and 500 nm. RESULTS: A statistically significant reduction in the VDI values determined using filters which absorb short-wavelength light was observed (p < 0.0001). The established VDIs in patients with VA logMAR <0.4 were 0.30 +/- 0.05 (95% CI, 0.26-0.36) for the lens alone, 0.20 +/- 0.04 (95% CI, 0.16-0.24) with the filter that completely absorbs wavelengths shorter than 450 nm, and 0.24 +/- 0.04 (95% CI, 0.20-0.28) with the filter that partially absorbs wavelengths shorter than 450 nm, which implies a 20 to 33% visual discrimination capacity increase. In addition, a decrease of VDI in at least one eye was observed in more than 90% of patients when using a filter. CONCLUSIONS: Short-wavelength light absorbance filters increase visual discrimination capacity under low illumination conditions in retinitis pigmentosa patients. Use of such filters constitutes a suitable method to improve visual quality related to intraocular light visual disturbances under low illumination conditions in this group of patients. PMID- 27391535 TI - Soft Contact Lens-Related Symptoms in North America and the United Kingdom. AB - PURPOSE: To characterize and compare the prevalence of soft contact lens-related (SCL) dryness symptoms in large populations of SCL wearers in North America (NAm) and the United Kingdom (UK). METHODS: SCL wearers from NAm (n = 1443) and UK (n = 932) sites completed self-administered questionnaires on SCL symptoms and wearing experiences. A categorization for contact lens-related dry eye (CL-DE) was applied that combined Contact Lens Dry Eye Questionnaire (CLDEQ) items on dryness frequency and intensity at the end of the day (CL-DE+ = constantly/frequently/sometimes plus intensity = 3-5, and CL-DE- = never/rarely plus intensity = 0-1, Marginal = all other ratings). Data were analyzed across regions and categories, with p-values <0.05 significant. RESULTS: Compared to UK wearers, those in NAm wore fewer toric and multifocal designs, and reported significantly longer average and comfortable wearing times (p < 0.001) but similar levels of general and end-of-day comfort. The prevalence of CL-DE+ differed between the UK and NAm: CL-DE+: 31 vs. 39%, Marginal CL-DE: 13 vs. 14%, and CL-DE-: 56 vs. 47%, p = 0.0001. Although daily disposable (DD) lenses were worn more commonly in the UK than NAm (33 vs. 10%, p < 0.0001), their use did not impact the overall prevalence of dryness symptoms. Between regions, NAm wearers reported significantly more frequent and intense end-of-day discomfort and dryness (p < 0.0001) and were significantly more likely to use treatments for CL related symptoms yet experienced a lower degree of relief. CONCLUSIONS: SCL wearers in NAm reported longer hours of wear with significantly more symptoms of dryness and discomfort. NAm wearers used dryness treatments more often, but experienced less relief than UK wearers. In both regions, the CL-DE categorization was useful to predict poorer comfort, shorter comfortable wearing time, and increased use of treatments. These results highlight the need to benchmark SCL performance locally or regionally to understand and focus on the challenges to the lens wearing experience. PMID- 27391536 TI - Changes in Myopia Prevalence among First-Year University Students in 12 Years. AB - PURPOSE: The aim of this study is to compare the changes in myopia prevalence among Portuguese first-year university students in 2002 and 2014 at the University of Minho. METHODS: The refractive status and axial length of first year students at the School of Sciences, University of Minho, were measured in 2014. Refractive error was measured with subjective refraction under cycloplegia and axial length was measured by optical biometry. The data were compared with those obtained from a similar cohort of 111 students in 2002. Myopia was defined as a mean spherical equivalent of <=-0.50D. A survey was conducted to know the routine of the participants. They were asked how many hours per week (hrs/wk) they had spent, on average in the previous year, watching TV, using the computer, studying, participating in manual hobbies, and participating in outdoor activities. RESULTS: In 2014, 75 students were assessed (15 male and 60 female) with a mean age (mean +/- SD) of 19.8 +/- 1.6 years (ranging from 18 to 24 years). The mean refractive error M (spherical equivalent) was -0.77 +/- 1.79D and the axial length was 23.74 +/- 1.19 mm. The prevalence of myopia was 41.3% (31 of 75). In 2002, the mean refractive error M was 0.01 +/- 1.53D, the axial length was 23.40 +/- 0.93 mm, and the myopia prevalence was 23.4% (26 of 111). The differences between myopia prevalence and mean refractive error are statistically significant (p < 0.05). A statistically significant increase in the number of hrs/wk spent on near activities (p < 0.05) was found. CONCLUSIONS: In 12 years, the prevalence of myopia among first-year university students at the School of Sciences of the University of Minho rose from 23.4 to 41.3%. This increase in myopia prevalence could be related to the lifestyle changes of the studied population. PMID- 27391537 TI - Topographic, Tomographic, and Aberrometric Characteristics of Post-LASIK Ectasia. AB - PURPOSE: To report the refractive, topographic, tomographic, and aberrometric characteristics of post-LASIK ectasia; to compare these characteristics with normal post-LASIK controls; and to propose a comprehensive system to grade the severity of post-LASIK ectasia. METHODS: The refraction, corrected distance visual acuity (CDVA), magnitude, and location of the steepest and thinnest point on the cornea, the highest anterior and posterior surface elevation, the radius of best fit sphere, corneal asphericity, and corneal aberrations were measured in 50 eyes of 29 patients with post-LASIK ectasia. These were compared with corresponding parameters in 50 eyes that did not develop ectasia for more than 1 year after LASIK. A logistic regression analysis was used to create a scoring system to grade the severity. RESULTS: Eyes with post-LASIK ectasia had significantly higher myopia with astigmatism and a lower CDVA than control eyes. Mean topographic toricity was 3.4 +/- 1.9D, mean keratometry at the steepest point was 55.32 +/- 6.63D, mean highest posterior elevation was 69.72 +/- 3 MUm, and mean coma was -2.06 +/- 1.2 MUm. All these parameters were significantly higher than corresponding values in the control group (p < 0.001 in all). Spherical aberration was more negative and the change in asphericity indicated significantly greater prolate shape of the cornea in eyes with post-LASIK ectasia compared to controls. Five parameters, namely, CDVA, spherical equivalent, highest posterior corneal elevation, spherical aberration, and corneal asphericity, were identified as significant predictors of post-LASIK ectasia and used to create a scoring system. CONCLUSION: Post-LASIK ectasia is characterized by significant changes in refraction, topography, tomography, and aberrometry. The proposed scoring system may be useful in diagnosing, grading, and monitoring post-LASIK ectasia. PMID- 27391538 TI - Repeatability and Reproducibility of Virtual Subjective Refraction. AB - PURPOSE: To establish the repeatability and reproducibility of a virtual refraction process using simulated retinal images. METHODS: With simulation software, aberrated images corresponding with each step of the refraction process were calculated following the typical protocol of conventional subjective refraction. Fifty external examiners judged simulated retinal images until the best sphero-cylindrical refraction and the best visual acuity were achieved starting from the aberrometry data of three patients. Data analyses were performed to assess repeatability and reproducibility of the virtual refraction as a function of pupil size and aberrometric profile of different patients. RESULTS: SD values achieved in three components of refraction (M, J0, and J45) are lower than 0.25D in repeatability analysis. Regarding reproducibility, we found SD values lower than 0.25D in the most cases. When the results of virtual refraction with different pupil diameters (4 and 6 mm) were compared, the mean of differences (MoD) obtained were not clinically significant (less than 0.25D). Only one of the aberrometry profiles with high uncorrected astigmatism shows poor results for the M component in reproducibility and pupil size dependence analysis. In all cases, vision achieved was better than 0 logMAR. A comparison between the compensation obtained with virtual and conventional subjective refraction was made as an example of this application, showing good quality retinal images in both processes. CONCLUSIONS: The present study shows that virtual refraction has similar levels of precision as conventional subjective refraction. Moreover, virtual refraction has also shown that when high low order astigmatism is present, the refraction result is less precise and highly dependent on pupil size. PMID- 27391540 TI - The Partington Prize 2017. PMID- 27391539 TI - Impact of Lens Care Solutions on Protein Deposition on Soft Contact Lenses. AB - PURPOSE: To evaluate the effect of four contemporary lens care solutions on total protein, total lysozyme, and active lysozyme extracted from three contact lens materials. METHODS: Adapted contact lens wearers were recruited at three sites, and all subjects were randomly assigned to daily wear of either etafilcon A, galyfilcon A, or senofilcon A for 2 weeks. Four lens care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and ClearCare) were used by each subject in random order with a new pair of lenses after a washout period between solutions of at least 4 days. After 2 weeks of daily wear, contact lenses were collected for analysis. Proteins were extracted from a subset of contact lenses (n = 568) and total protein, total lysozyme, and lysozyme activity were quantified using a modified Bradford assay, an enzyme-linked immunosorbent assay, and a micrococcal assay, respectively. RESULTS: Higher levels of total protein were extracted from etafilcon A when used with Biotrue compared to other solutions (p = 0.0001). There were higher levels of total lysozyme extracted from galyfilcon A lenses when used with PureMoist than with Biotrue or ClearCare (p < 0.006). Higher total lysozyme was extracted from senofilcon A when used with RevitaLens OcuTec compared to Biotrue (p = 0.002). Lower lysozyme activity was recovered from senofilcon A lenses with RevitaLens OcuTec when compared to all other care solutions (all p < 0.004). When Biotrue, PureMoist, or RevitaLens OcuTec were used, higher total lysozyme was extracted from galyfilcon A compared to senofilcon A (p < 0.01). When RevitaLens OcuTec was used, higher levels of active lysozyme were extracted from galyfilcon A compared to senofilcon A (p = 0.02). CONCLUSIONS: The ability of lens care solutions to remove protein from lenses varies depending upon the care solution composition and also the polymeric make-up of the contact lens material. PMID- 27391541 TI - Metabolic Characteristics of 16HBE and A549 Cells Exposed to Different Surface Modified Gold Nanorods. AB - Gold nanorods (AuNRs) have shown their great potential in cancer treatment due to their special physiochemical and optical properties, and the ease of surface modification. However, the molecular mechanism of biological effects induced by different surface modified AuNRs remains largely undetermined. Herein, this study for the first time systematically analyzed metabolic impacts of three surface modified AuNRs in cancer and noncancer cells detected by NMR and GC-FID/MS metabolomics and validated by molecular biological approach. It is found that positively and negatively charged AuNRs induce different metabolic consequences. Most importantly, it is found that the PEI-AuNRs display specific cytotoxicity to A549 cells while posing little impact on 16HBE cells. The cytotoxicity of PEI AuNRs to A549 cells is manifested in large disruptions to the cell metabolisms, which affects energy metabolism, choline metabolism, the hexosamine biosynthesis pathway, and oxidative stress to cells. The results of this study provide comprehensive molecular information on the distinct biological effects of different surface modified AuNRs, and can be valuable in designing purpose-driven nanomaterials. Most importantly, this work highlights the potential of metabolomics coupled with molecular biological techniques in screening antitumor nanodrugs and revealing the molecular mechanism of their biological effects. PMID- 27391543 TI - An Iminium Salt Organocatalyst for Selective Aliphatic C-H Hydroxylation. AB - The first examples of catalysis of aliphatic C-H hydroxylation by an iminium salt are presented. The method allows the selective organocatalytic hydroxylation of unactivated 3 degrees C-H bonds at room temperature using hydrogen peroxide as the terminal oxidant. Hydroxylation of an unactivated 2 degrees C-H bond is also demonstrated. Furthermore, improved functional group compatibility over other catalytic methods is reported in the form of selectivity for aliphatic C-H hydroxylation over alcohol oxidation. On the basis of initial mechanistic studies, an oxaziridinium species is proposed as the active oxidant. PMID- 27391542 TI - Inhibiting IL-1 signaling pathways to inhibit catabolic processes in disc degeneration. AB - Intervertebral disc degeneration is characterized by an imbalance between catabolic and anabolic signaling, with an increase in catabolic cytokines particularly IL-1beta, a key regulator of IVD degeneration. This study aimed to investigate intracellular signaling pathways activated by IL-1beta, and GDF-5 in the degenerate IVD to identify potential new therapeutic targets. Human NP cells were cultured in alginate beads to regain in vivo phenotype prior to stimulation with IL-1beta or GDF-5 for 30 min, a proteasome profiler array was initially utilized to screen activation status of 46 signaling proteins. Immunoflourescence was used to investigate activation of the NFkappaB pathway. Cell-based ELISAs were then deployed to confirm results for ERK1/2, p38 MAPK, c-jun, and IkappaB signaling. IHC was utilized to investigate native activation status within human IVD tissue between grades of degeneration. Finally, cells were stimulated with IL 1beta in the absence or presence of p38 MAPK, c-jun, JNK, and NFkappaB inhibitors to investigate effects on MMP3, MMP13, IL-1beta, IL-6, and IL-8 mRNA expression. This study demonstrated three key signaling pathways which were differentially activated by IL-1beta but not GDF-5; namely p38 MAPK, c-jun, and NFkappaB. While ERK 1/2 was activated by both GDF-5 and IL-1. Immunohistochemistry demonstrated p38 MAPK, c-jun, and NFkappaB were activated during human IVD degeneration and inhibition of these pathways reduced or abrogated the catabolic effects of IL 1beta, with inhibition of NFkappaB signaling demonstrating most widespread inhibition of IL-1beta catabolic effects. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:74-85, 2017. PMID- 27391544 TI - TNM-Classification for Lung Cancer: From the 7(th) to the 8(th) Edition. AB - Most tumors are staged according to the Tumor-Node-Metastasis (TNM) classification. For lung cancer a new edition was introduced in 2009 and generally applied since 2010. This 7(th) TNM-classification is based on a large, international retrospective database. Important changes were made regarding the T, N, M factors and specific subcategories were added. However, this 7(th) edition is still purely based on anatomical information. Other prognosticators such as laboratory results, histology, tumor markers and molecular genetic factors are not yet considered. To prepare the 8(th) TNM classification a prospective database developed by the International Association for the Study of Lung Cancer (IASLC), is currently enrolling patients from all continents. In this way, more precise and reliable data will become available on specific subdivisions of the T, N and M factors. If proven to be prognostically valid, other parameters will be included as histology, demographic data and specific biochemical and molecular predictive and prognostic factors. All centers with a large experience in thoracic oncology are encouraged to participate in this prospective database. PMID- 27391545 TI - Population-based retrospective study to investigate preexisting and new depression diagnosis among head and neck cancer patients. AB - This study aimed to estimate the pre-cancer prevalence and post-cancer incidence of depression in older adult head and neck cancer patients. Using SEER-Medicare files, cancer was identified from SEER data and depression diagnosis was identified using Medicare claims. Of 3533 head and neck cancer patients, 10.6% were diagnosed with depression during the two years prior to cancer diagnosis, and an additional 8.9% developed depression in the year following cancer diagnosis. This study supports the critical need of screening for depression throughout cancer diagnosis and treatment, as well as a preventative approach in depression development in the older head and neck cancer patient population. PMID- 27391546 TI - Perinatal and childhood factors and risk of prostate cancer in adulthood: MCC Spain case-control study. AB - BACKGROUND: In utero and early-life exposures are suspected to modulate the risk of prostate cancer. This study examines the influence of certain perinatal and childhood-related factors on prostate cancer risk overall and by Gleason score at biopsy. METHODS: MCC-Spain is a multicase-control study where 1088 histologically confirmed incident prostate cancer cases (aged 42-85years) and 1345 population based controls (aged 38-85years), frequency matched by age and province of recruitment, were recruited in 7 Spanish provinces. Self-reported perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with prostate cancer risk, globally and according to Gleason score at biopsy, was evaluated using logistic and multinomial regression mixed models, adjusting for age, family history of prostate cancer, educational level and body mass index one year before the interview, and including the province as a random effect term. RESULTS: Most perinatal factors were not related to prostate cancer risk, with the exception of middle-high socioeconomic level at birth (OR for high grade tumors=1.36; 95%CI=1.09-1.68). Regarding puberty, risk rose by 6% for each year of delayed onset (OR=1.06; 95%CI=1.01-1.10; p trend=0.016), with a clear excess of risk in men who reached puberty after age 15 (OR:1.35; 95%CI=1.08 1.68). A borderline significant positive association with prepubertal height was also observed (p trend=0.094). CONCLUSION: Some exposures experienced in utero and during adolescence, when the prostate is still maturing, might be relevant for prostate cancer risk in adulthood. PMID- 27391547 TI - Impact of geographic area level on measuring socioeconomic disparities in cancer survival in New South Wales, Australia: A period analysis. AB - BACKGROUND: Area-based socioeconomic measures are widely used in health research. In theory, the larger the area used the more individual misclassification is introduced, thus biasing the association between such area level measures and health outcomes. In this study, we examined the socioeconomic disparities in cancer survival using two geographic area-based measures to see if the size of the area matters. METHODS: We used population-based cancer registry data for patients diagnosed with one of 10 major cancers in New South Wales (NSW), Australia during 2004-2008. Patients were assigned index measures of socioeconomic status (SES) based on two area-level units, census Collection District (CD) and Local Government Area (LGA) of their address at diagnosis. Five year relative survival was estimated using the period approach for patients alive during 2004-2008, for each socioeconomic quintile at each area-level for each cancer. Poisson-regression modelling was used to adjust for socioeconomic quintile, sex, age-group at diagnosis and disease stage at diagnosis. The relative excess risk of death (RER) by socioeconomic quintile derived from this modelling was compared between area-units. RESULTS: We found extensive disagreement in SES classification between CD and LGA levels across all socioeconomic quintiles, particularly for more disadvantaged groups. In general, more disadvantaged patients had significantly lower survival than the least disadvantaged group for both CD and LGA classifications. The socioeconomic survival disparities detected by CD classification were larger than those detected by LGA. Adjusted RER estimates by SES were similar for most cancers when measured at both area levels. CONCLUSIONS: We found that classifying patient SES by the widely used Australian geographic unit LGA results in underestimation of survival disparities for several cancers compared to when SES is classified at the geographically smaller CD level. Despite this, our RER of death estimates derived from these survival estimates were generally similar for both CD and LGA level analyses, suggesting that LGAs remain a valuable spatial unit for use in Australian health and social research, though the potential for misclassification must be considered when interpreting research. While data confidentiality concerns increase with the level of geographical precision, the use of smaller area-level health and census data in the future, with appropriate allowance for confidentiality. PMID- 27391548 TI - Direct Observation of Luminescent Silver Clusters Confined in Faujasite Zeolites. AB - One of the ultimate goals in the study of metal clusters is the correlation between the atomic-scale organization and their physicochemical properties. However, direct observation of the atomic organization of such minuscule metal clusters is heavily hindered by radiation damage imposed by the different characterization techniques. We present direct evidence of the structural arrangement, at an atomic level, of luminescent silver species stabilized in faujasite (FAU) zeolites using aberration-corrected scanning transmission electron microscopy. Two different silver clusters were identified in Ag-FAU zeolites, a trinuclear silver species associated with green emission and a tetranuclear silver species related to yellow emission. By combining direct imaging with complementary information obtained from X-ray powder diffraction and Rietveld analysis, we were able to elucidate the main differences at an atomic scale between luminescent (heat-treated) and nonluminescent (cation-exchanged) Ag FAU zeolites. It is expected that such insights will trigger the directed synthesis of functional metal nanocluster-zeolite composites with tailored luminescent properties. PMID- 27391549 TI - Biocompatibility of a Novel Microfistula Implant in Nonprimate Mammals for the Surgical Treatment of Glaucoma. AB - PURPOSE: The purpose of this study was to evaluate the ocular safety of a novel microfistula implant and its composite materials in an animal model. METHODS: The anterior chambers of 12 rabbit eyes were injected with either glutaraldehyde cross-linked porcine gelatin extract or balanced salt solution and were followed by serial slit lamp examinations over 3 days. The eyes of 18 canines underwent microfistula implantation or a sham procedure. The animals were monitored over the subsequent 12 months, using serial slit lamp examinations, indirect ophthalmoscopy, tonometry, specular microscopy, and high-resolution ultrasonography. Ocular tissues were examined histopathologically on postoperative days 7, 30, 90, 180, and 365. RESULTS: Glutaraldehyde cross-linked porcine gelatin did not induce significant intraocular inflammation in the rabbit model. The microfistula implant was well tolerated and did not stimulate significant tissue response in the canine eye. The microfistula tube did not undergo structural change or degradation over the course of the study. CONCLUSIONS: In nonprimate mammals, the material composing the microfistula implant and the implant itself do not induce significant inflammation or tissue reaction. PMID- 27391550 TI - Homozygosity Mapping and Whole-Genome Sequencing Links a Missense Mutation in POMGNT1 to Autosomal Recessive Retinitis Pigmentosa. AB - PURPOSE: To identify the genetic cause in five families with autosomal recessive retinitis pigmentosa, a genetic disorder involving retinal degeneration and visual loss with high genetic heterogeneity. METHODS: We performed whole-genome single nucleotide polymorphism genotyping on 35 members from the five families to map the region of homozygosity shared by all patients. Whole-genome sequencing was then conducted on one of the patients and a novel variant was identified in POMGNT1 from the homozygous region, which was confirmed by Sanger sequencing and sequenced in all family members. Mutant and wild-type POMGNT1 were expressed in heterologous cells to assess enzyme activity. RESULTS: A 1.8-Mb homozygous region was identified at 1p34-p33 shared by all 17 patients. Whole-genome sequencing revealed a novel missense mutation in POMGNT1 (c.359A>C, p.Leu120Arg) from this homozygous region, which was shown to co-segregate with disease phenotype. The mutant protein carrying this missense mutation showed an approximately 80% decrease in POMGNT1 enzyme activity compared with the wild type. CONCLUSIONS: We identified a novel mutation in POMGNT1 that causes nonsyndromic autosomal recessive retinitis pigmentosa, adding to the genetic heterogeneity of this retinal disease. POMGNT1 encodes a glycosyltransferase in O-mannosyl glycosylation and was previously found to be responsible for a group of congenital muscular dystrophies called dystroglycanopathies. Our discovery suggests the involvement of O-mannosyl glycosylation in retinitis pigmentosa and presents an instance of POMGNT1 mutation that does not involve muscular dystrophy. PMID- 27391551 TI - Intravitreal Injection of Proinsulin-Loaded Microspheres Delays Photoreceptor Cell Death and Vision Loss in the rd10 Mouse Model of Retinitis Pigmentosa. AB - PURPOSE: The induction of proinsulin expression by transgenesis or intramuscular gene therapy has been shown previously to retard retinal degeneration in mouse and rat models of retinitis pigmentosa (RP), a group of inherited conditions that result in visual impairment. We investigated whether intraocular treatment with biodegradable poly (lactic-co-glycolic) acid microspheres (PLGA-MS) loaded with proinsulin has cellular and functional neuroprotective effects in the retina. METHODS: Experiments were performed using the Pde6brd10 mouse model of RP. Methionylated human recombinant proinsulin (hPI) was formulated in PLGA-MS, which were administered by intravitreal injection on postnatal days (P) 14 to 15. Retinal neuroprotection was assessed at P25 by electroretinography, and by evaluating outer nuclear layer (ONL) cellular preservation. The attenuation of photoreceptor cell death by hPI was determined by TUNEL assay in cultured P22 retinas, as well as Akt phosphorylation by immunoblotting. RESULTS: We successfully formulated hPI PLGA-MS to deliver the active molecule for several weeks in vitro. The amplitude of b-cone and mixed b-waves in electroretinographic recording was significantly higher in eyes injected with hPI-PLGA-MS compared to control eyes. Treatment with hPI-PLGA-MS attenuated photoreceptor cell loss, as revealed by comparing ONL thickness and the number of cell rows in this layer in treated versus untreated retinas. Finally, hPI prevented photoreceptor cell death and increased AktThr308 phosphorylation in organotypic cultured retinas. CONCLUSIONS: Retinal degeneration in the rd10 mouse was slowed by a single intravitreal injection of hPI-PLGA-MS. Human recombinant proinsulin elicited a rapid and effective neuroprotective effect when administered in biodegradable microspheres, which may constitute a future potentially feasible delivery method for proinsulin-based treatment of RP. PMID- 27391552 TI - Test-Retest Variability of Fundus-Tracked Perimetry at the Peripapillary Region in Open Angle Glaucoma. AB - PURPOSE: To examine the association between the measured level and local gradient of visual sensitivity on the magnitude of test-retest variability of its measurements at the peripapillary region using fundus-tracked perimetry in eyes with glaucoma. METHODS: A total of 30 participants with open angle glaucoma underwent three examinations in one eye on fundus-tracked perimetry using a stimulus pattern that sampled the peripapillary region densely. Factors associated with the magnitude of test-retest variability at each location were examined. RESULTS: There was no significant change in average pointwise sensitivity (PWS) between tests 1 and 2 (P = 0.855), but a significant reduction between tests 2 and 3 (P < 0.001). Therefore, all subsequent analyses were performed only between tests 1 and 2. Multivariate analyses revealed that the magnitude of test-retest variability at a given location was significantly associated with its average sensitivity and gradient of sensitivity relative to the immediately adjacent locations (P <= 0.001), meaning that locations with low levels of sensitivity (4-18 dB) with low gradients of sensitivity (<2 dB/location) had a 90% test-retest limit of +/-5.83 dB, compared to a limit of +/ 10.65 dB in areas of high gradients of sensitivity (>4 dB/location). CONCLUSIONS: On a pointwise basis, the test-retest variability of visual sensitivity in glaucoma is not just related to its measured level, but also its local gradient when using fundus-tracked perimetry. Locations with low sensitivity do not necessarily demonstrate very high test-retest variability, depending on the local uniformity of visual field damage. PMID- 27391554 TI - Evaluating the Effectiveness of an Established Community-Based Eccentric Viewing Rehabilitation Training Model-the EValuation Study. AB - PURPOSE: This study evaluated the community-based eccentric viewing (EV) training offered across the United Kingdom by the Macular Society. Volunteer trainers deliver free one-to-one training, usually in learners' homes. They also share information about lighting, magnification, social support, and low-vision technology. METHODS: The audio-recorded reading performance of learners was compared before and after training. Telephone questionnaires were used to assess life satisfaction, amount of reading performed, and health- and vision-related quality of life. Learners were also interviewed to obtain their subjective opinions. RESULTS: A total of 121 learners completed all stages of the study. There was no significant change in maximum reading speed. A statistically significant (P < 0.001) but small improvement in both critical print size and threshold print size was found, but frequency and duration of reading did not increase. There was a borderline significant (P = 0.022) increase in "life satisfaction" for the learners, but a highly significant (P < 0.001) decrease in their "positive affect." There was no change in health- or vision-related quality of life, or in the difficulty experienced in performing everyday tasks. However, according to learner interviews, 72% felt they had achieved a positive outcome from the training, and 75% felt they had received helpful advice in addition to the EV training. CONCLUSIONS: The lack of improvement of reading speed and modest improvement in threshold print size should be interpreted in the context of the unique features of this EV program, since many learners who would seem to have limited scope for improvement still undertake the training. PMID- 27391553 TI - Specific Inner Retinal Layer Cell Damage in an Autoimmune Glaucoma Model Is Induced by GDNF With or Without HSP27. AB - PURPOSE: Previously, immunization of rats with ocular antigens induced retinal ganglion cell (RGC) degeneration. We investigated the effect of immunization with glial cell line-derived neurotrophic factor (GDNF) or GDNF in combination with heat shock protein 27 (GDNF+HSP) on RGCs and other retinal cells. METHODS: Rats were immunized with GDNF or GDNF+HSP. After 4 weeks, retinas were stained with Brn-3a and NeuN to quantify RGCs. GFAP and vimentin staining were used to investigate macroglia. Microglia were marked with Iba1 and ED1. Amacrine cells were labeled with parvalbumin and ChAT. Photoreceptors were evaluated with rhodopsin and opsin staining and bipolar cells with PKCalpha and recoverin. For these cell types, Western blotting was also performed. RESULTS: Retinas of immunized animals showed a significant loss of Brn-3a+ and NeuN+ RGCs. No significant changes could be observed in regard to macroglia. An increase in Iba1+ microglia was detected in both groups, but little change in regard to activated microglia. A loss of cholinergic amacrine cells was seen in the GDNF+HSP group by immunohistochemistry and in both groups via Western blot analysis. AII amacrine cells, bipolar cells, and photoreceptors were not affected. CONCLUSIONS: Immunizations led to loss of RGCs and cholinergic amacrine cells and a strong increase in microglial cells. Our data suggest that RGC loss is the consequence of immunization with GDNF. Astrocyte activity and its neuroprotective effects seem to be inhibited by GDNF immunization. We presume more complex interactions between GDNF and HSP27 because no additive effects could be observed. PMID- 27391556 TI - Esophagectomy for end-stage achalasia. AB - End-stage achalasia is rarely effectively addressed with conservative treatments, as food must traverse a serpiginous route to reach the stomach. Botox injections in the setting of end-stage achalasia will likely provide minimal temporary palliation at best, pneumatic dilation has higher risks of perforation, and laparoscopic myotomy, while minimally invasive, has presented poor results. Under these circumstances, there are many proposed procedures to restore a viable alimentary condition to patients, from partial to subtotal resection of the esophagus; each of procedures confers both advantages and specific risks. Subtotal esophagectomy must be indicated for end-stage disease (tortuous or sigmoid esophagus) and persistent dysphagia after failed interventions. When performed by experienced hands, the procedure can be undertaken successfully, with acceptable postoperative morbidity and mortality, improvement of symptoms, and a good long-term quality of life in the majority of patients. PMID- 27391555 TI - Assessing people with dementia: the role of the aged care assessment team and memory clinics. AB - BACKGROUND: A cross-sectional survey of all patients reviewed by the aged care assessment team (ACAT) service and memory clinics between 1 January and 31 December 2012. The ACAT catchment included an estimated 14 325 people over the age of 70. AIMS: To determine the numbers and outcomes of assessments for cognitive problems by the ACAT and hospital memory clinics for patients within a single ACAT catchment area. METHODS: Data collected included patient demographics, diagnoses, referral and pharmacological treatment. Flow of referrals to the services that diagnose and manage dementia, and the number of incident dementia cases diagnosed in 2012 were determined. RESULTS: The ACAT service assessed 1005 patients from the catchment, of which 241 patients already had a diagnosis of dementia. When compared with the estimated dementia prevalence in Australia, 19% of prevalent dementia cases (n = 1260) within the catchment were reviewed by the ACAT. The two memory clinics saw a combined 186 new referrals (91 and 95 respectively) from within the catchment, with a total of 82 patients (22 and 60 respectively) receiving a new diagnosis of dementia. Using Australian estimates of dementia incidence, this would suggest 29% of 286 incident cases were managed through these memory clinics. CONCLUSIONS: Geriatric services are responsible for the assessment and management of a large proportion of the estimated number of patients with dementia in this catchment area. Further resourcing and standardisation of the pathways to dementia assessment is required in Australia in order to diagnose and manage effectively people with dementia. PMID- 27391557 TI - Rhenium(I)-Catalyzed Generation of alpha,beta-Unsaturated Carbene Complex Intermediates from Propargyl Ethers for the Preparation of Cycloheptadiene Derivatives. AB - The rhenium(I)-catalyzed generation of alpha,beta-unsaturated carbene complex intermediates from easily available propargyl ethers was achieved for the concise construction of cycloheptadiene derivatives through the formal [4+3] cycloaddition reaction with siloxydienes. PMID- 27391558 TI - Expression of podoplanin and TGF-beta in glandular odontogenic cyst and its comparison with developmental and inflammatory odontogenic cystic lesions. AB - BACKGROUND: The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions. METHODS: A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05). RESULTS: Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs. CONCLUSIONS: Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression. PMID- 27391559 TI - Considerable Enhancement of Emission Yields of [Au(CN)2(-)] Oligomers in Aqueous Solutions by Coexisting Cations. AB - The photophysical properties of [Au(CN)2(-)] oligomers in aqueous solutions were investigated as functions of coexisting cations as well as the viscosity and temperature of solutions. A solution of [Au(CN)2(-)] in the concentration range of 0.03-0.2 mol/dm(3) exhibited emission peaks at 460-480 nm because of the presence of oligomers larger than trimers. Although the emission yields (phiem) of K[Au(CN)2] solutions were <1%, it considerably increased to 43% when 1.0 mol/dm(3) tetraethylammonium chloride (Et4NCl) was added. The lifetimes of the main emission bands were also significantly varied with additional salts, e.g., KCl, 15 ns; Et4NCl, 520 ns. The time-resolved emission measurements of [Au(CN)2( )] in a water/glycerol mixture indicated that the lifetimes were almost directly proportional to the inverse of the viscosity of the solution. On the other hand, the intrinsic lifetimes of dimers and trimers with weak emission in shorter wavelength regions were very short and independent of the viscosity of the solutions and coexisting cations (dimer, ~25 ps; trimer, ~2 ns). These results indicated that the deactivation of the excited-state [Au(CN)2(-)]n oligomers (n >= 4) was dominated by the dissociation of the oligomers to a shorter species (dimer or trimer). The hydrophobic interactions between tetraalkylammonium cations and CN ligands remarkably stabilized the larger oligomers and suppressed the dissociation of the excited-state oligomers, which enhanced the emission yield of the oligomers. This work provides a new method of "exciplex tuning" by changing the environment of excited-state [Au(CN)2(-)]n oligomers. PMID- 27391560 TI - Barriers to Knowledge Translation Regarding the Use of Probiotics as a Risk Reduction Strategy for Necrotizing Enterocolitis. AB - BACKGROUND: Increasingly, evidence supports enteral probiotics are an important risk-reduction strategy for necrotizing enterocolitis (NEC) among very low birth weight and extremely low birth-weight preterm infants. Yet, the majority of providers remain reluctant to implement practice changes. PURPOSE: The aim of this study was to better understand the discrepancy between the available evidence and clinical practice regarding the use of probiotics and other NEC prevention strategies in New Jersey. METHODS: Using an exploratory descriptive design, a multimodal interprofessional survey was developed and executed to elicit intensive care nursery provider knowledge, views, and current practice. RESULTS: Although the sample size was small (N = 29), approximately one-half of respondents familiar with the literature rated the quality of the evidence regarding probiotics as "above average" to "excellent." These respondents were "very likely" to "extremely likely" to recommend probiotics as an NEC prevention strategy; however, none actually prescribed this intervention. The most important reason respondents did not prescribe probiotics was the focus on providing exclusive maternal and donor breast milk feedings. Other confounding factors included provision of oral colostrum care, standardized feeding protocols, and withholding feedings during blood transfusion. IMPLICATIONS FOR PRACTICE: Study results suggested that some providers (primarily nurses) were not familiar with probiotic literature, which may contribute to deficits in knowledge translation to practice. IMPLICATIONS FOR RESEARCH: Areas for future study include identifying improved mechanisms for knowledge dissemination, recognizing and addressing barriers and facilitators to knowledge translation, and understanding how probiotics fit and/or contrast with other NEC risk-reduction strategies in the research and clinical settings. PMID- 27391561 TI - Health Literacy and Preferences for Sources of Child Health Information of Mothers With Infants in the Neonatal Intensive Care Unit. AB - BACKGROUND: Parents of infants hospitalized in the neonatal intensive care unit (NICU) frequently need guidance to prepare them for the care and health promotion of their child after hospital discharge. The health literacy of the parents should be considered so that education can be tailored to meet their needs. It is also important to understand the parents' preferences for how, and from whom, they receive education. PURPOSE: The purpose of this study was to identify health literacy levels of parents of infants in an NICU and preferences for who they want to provide them with education. METHODS: An exploratory, descriptive design was used to assess participant health literacy and preferences for obtaining child health information. Only mothers (no fathers) with babies in the NICU were available to complete the survey. Mean participant age was 26.4 years (SD = 6.7). RESULTS: Participants had a mean Rapid Estimate of Adult Literacy in Medicine, Revised, score of 5.64 (SD = 2.4), indicating a low level of health literacy. Questions regarding when to administer medication were correctly answered by 69% of participants. Proper medication dosage was understood by 92% of participants; however, only 30% were able to correctly convert measurements. One-on-one discussions with a physician were the preferred source of health information for 80% of participants. IMPLICATIONS FOR PRACTICE/RESEARCH: The current exploratory study provides new information that will help inform the development of future studies and increase awareness of nurses regarding health literacy and the specific types of skills for which parents need the most help. PMID- 27391562 TI - Health Literacy Among Parents of Newborn Infants. AB - BACKGROUND: Health Literacy is the ability to obtain, process, and understand health information to make knowledgeable health decisions. PURPOSE: To determine baseline health literacy of neonatal intensive care unit (NICU) parents at a tertiary care hospital during periods of crucial information exchange. METHODS: Health literacy of English-speaking NICU parents was assessed using the Newest Vital Sign (NVS) on admission (n = 121) and discharge (n = 59). A quasi-control group of well-baby nursery (WBN) parents (n = 24) and prenatal obstetric clinic (PRE) parents (n = 18) were included. A single, Likert-style question measured nurses' assessment of parental comprehension with discharge teaching. Suspected limited health literacy (SLHL) was defined as the NVS score of 3 or less. FINDINGS/RESULTS: Forty-three percent of parents on NICU admission and 32% at NICU discharge had SLHL (P < .01). SLHL for WBN and PRE parents was 25% and 58%, respectively. Parental age, gender, location, and history of healthcare-related employment were not associated with health literacy status at any time point. Thirty-nine percent of NICU parents and 25% of WBN parents with SLHL at time of admission/infant birth had a college education. Nurse subjective measurement of parental comprehension of discharge instructions was not correlated to the objective measurement of health literacy (P = .26). IMPLICATIONS FOR PRACTICE: SLHL is common during peak time periods of complex health discussion in the NICU, WBN, and PRE settings. NICU providers may not accurately gauge parents' literacy status. IMPLICATIONS FOR RESEARCH: Methods for improving health communication are needed. Studies should evaluate SLHL in a larger NICU population and across different languages and cultures. PMID- 27391563 TI - First Golden Hour of Life: A Quality Improvement Initiative. AB - BACKGROUND: Very low birth-weight (<1500 g) infants are vulnerable to their environment during the first hour after birth. We designed an evidence-based golden hour protocol (GHP) with a goal to stabilize and perform admission procedures within 1 hour of birth at a level IIIB neonatal intensive care unit (NICU). PURPOSE: The aim of this quality improvement project was to ascertain whether an evidence-based GHP would improve care efficiency and short-term outcomes. METHODS: Rapid cycles of change using Plan Do Study Act were utilized to document progress and gain knowledge during the quality improvement project. Measures were plotted with statistical process control methods (SPC), which analyzed improvement over time. RESULTS: Both admission temperature and glucose level means were within reference range throughout the project and predicted a stable process. We observed significantly decreased time to initiation of intravenous fluids and antibiotics. An upward trend of surfactant administration within the first 2 hours of life was also observed. IMPLICATIONS FOR PRACTICE: The use of a GHP provided an organized approach to admission procedures and care. By using a checklist and recording intervention times, NICU caregivers were more aware of time management for each intervention and were able to decrease time to initiation of intravenous fluids and antibiotics. IMPLICATIONS FOR RESEARCH: Future research should focus on establishing normal blood pressure ranges and safe pain management during the "golden hour" and beyond. Future quality improvement should focus on improving subsequent temperature and blood glucose levels after admission umbilical artery and venous catheter placement. PMID- 27391564 TI - Infant Medical Trauma in the Neonatal Intensive Care Unit (IMTN): A Proposed Concept for Science and Practice. AB - BACKGROUND: Trauma is an innately subjective experience ensuing from a deeply distressing event. Research has demonstrated that while the environment of the neonatal intensive care unit (NICU) is capable of providing extraordinary lifesaving measures following birth, the experience may be disruptive to several key aspects of early development, placing infants at risk for adverse behavioral, cognitive, and emotional outcomes. PURPOSE: This article provides rationale for the concept of Infant Medical Trauma in the NICU (IMTN) as a means of describing this unique stress experience. A triad of cumulative early life NICU experiences (stress, parental separation, and pain) is proposed to influence an infant's swinging neurodevelopmental pendulum amid the potential outcomes of risk and resilience. IMPLICATIONS FOR PRACTICE AND RESEARCH: Creating language that describes the infant experience brings meaning and calls caregivers and parents to action to consider strategies that may improve long-term health. Actively seeking opportunities to decrease the allostatic load of at-risk infants may support an infant's pendulum to swing toward a path of resilience, thereby moderating his or her early life adverse experience. PMID- 27391565 TI - Surveillance and Isolation of Methicillin-Resistant Staphylococcus aureus Colonization in the Neonatal Intensive Care Unit. AB - BACKGROUND: Neonatal sepsis causes 1.4 million (36%) neonatal deaths annually. Staphylococcus aureus (SA), a common skin pathogen, remains the second leading cause of late-onset sepsis in the neonatal intensive care unit (NICU). Methicillin-resistant Staphylococcus aureus (MRSA), a resistant strain of SA, has created a significant global communicable health risk, especially in the NICU. PURPOSE: To examine evidence related to NICU infection control practices surrounding MRSA surveillance, identification, and isolation in response to the clinical question, "What strategies should be universally implemented in the NICU to identify and prevent the spread of MRSA?" METHODS/SEARCH STRATEGY: Databases were examined for articles on the topical area of MRSA in the neonate. Key terms were used to streamline the search, resulting in 20 primary works and 3 guideline/consensus statements considered imperative in response to the clinical questions. FINDINGS/RESULTS: Hand hygiene remains the cornerstone to sound infection control practice. Colonization often leads to systemic infection, with smaller neonates at greatest risk. Hospital infection control compliance has improved outcomes. MRSA surveillance has reduced horizontal spread. No universal, specific recommendations exist to guide surveillance and management of MRSA in the NICU. IMPLICATIONS FOR PRACTICE: Standardized guidelines with procedures for hand hygiene, patient surveillance and isolation, and patient cohorting with recommended staffing patterns should guide practice in the NICU. Both MRSA culture and polymerase chain reaction effectively identify positive patients. Decolonization practices are not yet clear. IMPLICATIONS FOR RESEARCH: Evaluation of standard isolation practices versus outbreak response and approaches to neonatal decolonization should be evaluated for efficacy, safety, and resistance. PMID- 27391566 TI - The Use of Human Milk and Breastfeeding in the Neonatal Intensive Care Unit: Position Statement 3065. PMID- 27391567 TI - The Implications of Parental Consanguinity on the Care of Neonates. AB - BACKGROUND: Approximately 6% of births worldwide, 7.9 million children, are born with a serious genetic congenital abnormality each year. A factor thought to increase the prevalence of birth defects is parental consanguinity, which is a social custom practiced in at least 20% of the world's population. PURPOSE: The purpose of this article is to explore the relationship between consanguinity and congenital defects. This article also aims to enhance neonatal healthcare practitioners' comprehension of its implications for practice and research. METHODS: A review of literature was compiled from a search of the online databases Cumulative Index of Nursing and Allied Health (CINAHL), PubMed, EBSCO MegaFILE, and Google Scholar. RESULTS: Literature pertinent to this topic primarily consists of research studies that examine the inbreeding depression phenomenon through comparison of the prevalence of birth defects among the offspring of consanguineous and nonconsanguineous couples. Current studies indicate that the progeny of consanguineous couples are at an increased risk of congenital defects compared with those of nonconsanguineous couples. IMPLICATIONS FOR PRACTICE: Consanguinity is one risk factor among many that can lead to a major birth defect. Relationships between consanguineous populations and neonatal healthcare practitioners such as registered nurses, advanced practice nurses, and physicians could significantly alter neonatal health outcomes. Specific recommendations such as genetic counseling and therapeutic communication are discussed. IMPLICATIONS FOR RESEARCH: Further studies need to investigate the connection between consanguinity and birth defects while controlling for nongenetic variables. Moreover, a focus on consanguineous communities in the United States would prove beneficial. PMID- 27391568 TI - NANN Provides Education About Neonatal Abstinence Syndrome and Zika Virus Infection and Prepares Neonatal Nurses to Be Advocates for Their Profession and Their Patients. PMID- 27391569 TI - Sacred Spaces: Religious and Secular Coping and Family Relationships in the Neonatal Intensive Care Unit. AB - BACKGROUND: Preterm birth is an unanticipated and stressful event for parents. In addition, the unfamiliar setting of the intensive care nursery necessitates strategies for coping. PURPOSE: The primary study objective of this descriptive study was to determine whether secular and religious coping strategies were related to family functioning in the neonatal intensive care unit. METHODS: Fifty two parents of preterm (25-35 weeks' gestation) infants completed the Brief COPE (secular coping), the Brief RCOPE (religious coping), and the Family Environment Scale within 1 week of their infant's hospital admission. FINDINGS: This descriptive study found that parents' religious and secular coping was significant in relation to family relationship functioning. Specifically, negative religious coping (ie, feeling abandoned or angry at God) was related to poorer family cohesion and use of denial. IMPLICATIONS FOR PRACTICE: These findings have relevance for interventions focused toward enhancing effective coping for families. IMPLICATIONS FOR RESEARCH: Further study of religious and secular coping strategies for neonatal intensive care unit families is warranted in a larger more diverse sample of family members. PMID- 27391571 TI - Maternal risk exposure during pregnancy and infant birth weight. AB - BACKGROUND: Birth weight is an important determinant of an infant's immediate and future health. AIM: This study examined associations between selected maternal psychosocial and environmental risk factors during pregnancy and subsequent infant birth weight, utilising data from the South African Birth to Twenty Plus (Bt20+) birth cohort study. SUBJECTS: Exposure to nine maternal risks were assessed in 1228 women who completed an antenatal questionnaire and whose infants were delivered within a seven-week period. OUTCOME MEASURES: The outcome of interest was infant birth weight. Birth weight z-scores (BWZ) were calculated using the World Health Organization Child Growth Standards. Bivariate analyses and multiple regression models were used to identify significant risk factors. RESULTS: The mean infant birth weight was 3139g (SD 486g), with a significant advantage in mean birth weight for male infants of 73g (p=0.008). Being unsure or not wanting the pregnancy was associated with a ~156g reduction in infant birth weight (beta=-0.32; 95% CI -0.51; -0.14). Tobacco use during pregnancy was also negatively associated with BWZ (beta=-0.32; 95% CI -0.59; -0.05). Exposure to both significant risk factors (tobacco use and pregnancy wantedness) was associated with cumulative reductions in birth weight, particularly among boys. CONCLUSIONS: This study reinforces the importance of risks related to maternal attitudes and behaviours during pregnancy, namely unwanted pregnancy and tobacco use, which significantly lowered birth weight. Both identified risks are amenable to public health policy and programme intervention. PMID- 27391570 TI - Aging of mice is associated with p16(Ink4a)- and beta-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells. AB - Senescent cells (SCs) have been considered a source of age-related chronic sterile systemic inflammation and a target for anti-aging therapies. To understand mechanisms controlling the amount of SCs, we analyzed the phenomenon of rapid clearance of human senescent fibroblasts implanted into SCID mice, which can be overcome when SCs were embedded into alginate beads preventing them from immunocyte attack. To identify putative SC killers, we analyzed the content of cell populations in lavage and capsules formed around the SC-containing beads. One of the major cell types attracted by secretory factors of SCs was a subpopulation of macrophages characterized by p16(Ink4a) gene expression and beta galactosidase activity at pH6.0 (beta-gal(pH6)), thus resembling SCs. Consistently, mice with p16(Ink4a) promoter-driven luciferase, developed bright luminescence of their peritoneal cavity within two weeks following implantation of SCs embedded in alginate beads. p16(Ink4a)/beta-gal(pH6)-expressing cells had surface biomarkers of macrophages F4/80 and were sensitive to liposomal clodronate used for the selective killing of cells capable of phagocytosis. At the same time, clodronate failed to kill bona fide SCs generated in vitro by genotoxic stress. Old mice with elevated proportion of p16(Ink4a)/beta-gal(pH6) positive cells in their tissues demonstrated reduction of both following systemic clodronate treatment, indicating that a significant proportion of cells previously considered to be SCs are actually a subclass of macrophages. These observations point at a significant role of p16(Ink4a)/beta-gal(pH6)-positive macrophages in aging, which previously was attributed solely to SCs. They require re-interpretation of the mechanisms underlying rejuvenating effects following eradication of p16(Ink4a)/beta-gal(pH6)-positive cells and reconsideration of potential cellular target for anti-aging treatment. PMID- 27391572 TI - Effects of pre- and post-natal lipid-based nutrient supplements on infant development in a randomized trial in Ghana. AB - BACKGROUND: Maternal and infant undernutrition is negatively associated with infant development. AIMS: We tested the hypothesis that provision of small quantity lipid-based nutrient supplements (SQ-LNS) to pregnant women and infants positively affects infant development. STUDY DESIGN: In a partially double-blind randomized controlled trial, we compared the following daily maternal supplements during pregnancy and until 6months post-partum: iron/folic acid capsule (IFA), capsule containing 18 micronutrients (MMN), or 20g SQ-LNS. Children in the SQ-LNS group also received SQ-LNS from age 6 to 18months. The study is registered as NCT00970866. SUBJECTS: 1320 pregnant women in Ghana enrolled in the trial; 1173 of their children participated in developmental assessment. OUTCOME MEASURES: We monitored the acquisition of 10 developmental milestones monthly by parental report, observed the attainment of 6 motor milestones at 6, 12, and 18months, and conducted detailed assessment of motor, language, socio-emotional, and executive function at 18months. RESULTS: By researcher observation, a greater percentage of children in the SQ-LNS group (53%) was able to walk alone at 12months than in the IFA group (43%; RR=1.23, 95% CI=1.02-1.49; p=0.025). We found no significant differences between groups in milestone acquisition by parent report or in any scores at 18months. The difference in mean z-scores between groups ranged from 0.03-0.13 for motor (p=0.84), 0.01-0.08 for language (p=0.46), 0.01-0.02 for socio-emotional (p=0.75), and 0.00-0.02 for executive function (p=0.95). CONCLUSION: While provision of maternal and child SQ-LNS in Ghana may affect walking at 12months, it did not affect infant development at 18months. PMID- 27391573 TI - Influence of hyperbilirubinemia on neonatal sucking. AB - BACKGROUND: Mothers of hyperbilirubinemic newborns frequently report to us that their infant is feeding poorly. As poor feeding in an extremely hyperbilirubinemic newborn may be an early sign of bilirubin encephalopathy, we hypothesized that neonatal hyperbilirubinemia would suppress the volume of feed ingested and diminish sucking parameters in comparison with minimally jaundiced neonates. OBJECTIVE: To determine whether hyperbilirubinemia does diminish feeding and sucking in neonates. STUDY DESIGN: Neonates in a well-baby nursery with serum total bilirubin (STB) >=15.0mg/dL were compared with those with transcutaneous bilirubin <=10mg/dL. Neonur, a modification of Krohn's Nutritive Sucking Apparatus, was used to quantify sucking parameters. Measurements during a 5min feeding period included volume ingested (measured manually), number of sucks, average maximum sucking pressure, number of bursts, average burst duration, pause between bursts duration, number of sucks per burst, and average intersuck interval. Outcome measures were volume ingested and, presuming decreased volume, sucking parameter analysis would determine the component affected by hyperbilirubinemia. RESULTS: 17 hyperbilirubinemic newborns (STB 17.8+/-1.6mg/dL) were compared with 24 controls, all with transcutaneous bilirubin <10.0mg/dL. The volume of feed ingested was similar between the hyperbilirubinemic newborns and controls (30.00 [20.00-42.50] ml vs. 25.00 [15.00 30.00] ml, p=0.2) (median [95% confidence interval]). No significant differences were noted in any of the other sucking parameters measured. CONCLUSIONS: At concentrations of STB in the range of 15-20mg/dL, hyperbilirubinemia did not diminish feed volume or sucking parameters in term newborns. Poor feeding in moderately hyperbilirubinemic newborns cannot be attributed to the level of bilirubin per se. PMID- 27391574 TI - Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome. AB - Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ?40 years and marrow blast ?70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype. PMID- 27391575 TI - Allogeneic hematopoietic cell transplantation in patients ?70 years: which patients may benefit? PMID- 27391576 TI - Reprogramming of Notch1-induced acute lymphoblastic leukemia cells into pluripotent stem cells in mice. PMID- 27391577 TI - Search for familial clustering of cancer in monoclonal gammopathy of unknown significance. PMID- 27391578 TI - SwissSimilarity: A Web Tool for Low to Ultra High Throughput Ligand-Based Virtual Screening. AB - SwissSimilarity is a new web tool for rapid ligand-based virtual screening of small to unprecedented ultralarge libraries of small molecules. Screenable compounds include drugs, bioactive and commercial molecules, as well as 205 million of virtual compounds readily synthesizable from commercially available synthetic reagents. Predictions can be carried out on-the-fly using six different screening approaches, including 2D molecular fingerprints as well as superpositional and fast nonsuperpositional 3D similarity methodologies. SwissSimilarity is part of a large initiative of the SIB Swiss Institute of Bioinformatics to provide online tools for computer-aided drug design, such as SwissDock, SwissBioisostere or SwissTargetPrediction with which it can interoperate, and is linked to other well-established online tools and databases. User interface and backend have been designed for simplicity and ease of use, to provide proficient virtual screening capabilities to specialists and nonexperts in the field. SwissSimilarity is accessible free of charge or login at http://www.swisssimilarity.ch . PMID- 27391579 TI - Contemplating Bretscher's View that the Tritope Model is 'Implausible'. AB - There is, at present, only two models of the TCR structure-function relationship. These are referred to here as the Standard (Centric) model and the Tritope model. While I have argued that the Standard model is untenable and proposed the Tritope to replace it, Bretscher has argued that the Tritope model is 'implausible' and throws his support for the Standard model. This essay analyses the implausibility argument concluding that it is unfounded. PMID- 27391580 TI - The Paediatric Admission Quality of Care (PAQC) score: designing a tool to measure the quality of early inpatient paediatric care in a low-income setting. AB - BACKGROUND: Evaluating clinician compliance with recommended steps in clinical guidelines provides one measure of quality of process of care but can result in a multiplicity of indicators across illnesses, making it problematic to produce any summative picture of process quality, information that may be most useful to policy-makers and managers. OBJECTIVE: We set out to develop a clinically logical summative measure of the quality of care provided to children admitted to hospital in Kenya spanning the three diagnoses present in 60% or more of admissions that would provide a patient-level measure of quality of care in the face of comorbidity. METHODS: We developed a conceptual model of care based on three domains: assessment, diagnosis and treatment of illnesses. Individual items within domains correspond to recommended processes of care within national clinical practice guidelines. Summative scores were created to reduce redundancy and enable aggregation across illnesses while maintaining a clear link to clinical domains and our conceptual model. The potential application of the score was explored using data from more than 12 000 children from eight hospitals included in a prior intervention study in Kenya. RESULTS: Summative scores obtained from items representing discrete clinical decision points reduced redundancy, aided balance of score contribution across domains and enabled direct comparison of disease-specific scores and the calculation of scores for children with comorbidity. CONCLUSION: This work describes the development of a summative Paediatric Admission Quality of Care score measured at the patient level that spans three common diseases. The score may be an efficient tool for assessing quality with an ability to adjust for case mix or other patient-level factors if needed. The score principles may have applicability to multiple illnesses and settings. Future analysis will be needed to validate the score. PMID- 27391581 TI - The Omental Pedicle Flap in Dogs Revised and Refined: A Cadaver Study. AB - OBJECTIVE: To expand current knowledge on the canine omental vasculature and refine the existing lengthening technique of the canine omentum. STUDY DESIGN: Ex vivo study. ANIMALS: Canine cadavers (n=20). METHODS: In 10 canine cadavers the omental arteries were mapped using intravascular latex injection and these results were used to create an omental pedicle flap based on the splenic artery in 10 additional cadavers. The operating range of the flap was recorded with particular attention to the main regions of interest for omental transposition in dogs (axillary and inguinal regions). RESULTS: The superficial and deep omental leaves were each predominantly supplied by a left and a right marginal omental artery that anastomosed near the caudal omental border into a superficial and a deep omental arch, respectively. Anastomoses between arteries of the superficial and the deep omental leaves were weak and inconsistent, except for 1 anastomosis that was found in 8 of 10 dogs. By transposing the intact omentum, the right axilla could be reached in 3 dogs, both axillae in 1 dog, and both groins in all cadavers. In all cases, the omental pedicle reached to and beyond the axillary and inguinal regions. By unfolding the pedicle leaves, the width of the pedicle tip could be doubled. CONCLUSION: When lengthening the omentum is necessary to reach extra-abdominal structures, the omental pedicle flap based on the splenic artery appears to preserve the omental vascular supply. These observations warrant further clinical trials to evaluate this new omtental flap technique in vivo. PMID- 27391582 TI - Dispersive liquid-liquid microextraction based on solidification of floating organic droplet for the determination of triazine and triazoles in mineral water samples. AB - A simple, rapid, and sensitive method for the determination of atrazine, simazine, cyproconazole, tebuconazole, and epoxiconazole in mineral water employing the dispersive liquid-liquid microextraction with solidification of a floating organic drop with determination by liquid chromatography tandem mass spectrometry has been developed. A mixed solution of 250 MUL 1-dodecanol and 1250 MUL methanol was injected rapidly into 10 mL aqueous solution (pH 7.0) with 2% w/v NaCl. After centrifugation for 5 min at 2000 rpm, the organic solvent droplets floated on the surface of the aqueous solution and the floating solvent solidified. The method limits of detection were between 3.75 and 37.5 ng/L and limits of quantification were between 12.5 and 125 ng/L. The recoveries ranged from 70 to 118% for repeatability and between 76 and 95% for intermediate precision with a relative standard deviation from 2 to 18% for all compounds. Low matrix effect was observed. The proposed method can be successfully applied in routine analysis for determination of pesticide residues in mineral water samples, allowing for monitoring of triazine and triazoles at levels below the regulatory limits set by international and national legislations. PMID- 27391584 TI - Risk Factors for Hepatocellular Carcinoma in Cirrhotic Patients with Chronic Hepatitis B. AB - AIMS: To investigate the clinical and genetic risk factors associated with hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB). METHODS: Nine hundred forty-nine Chinese Han patients with CHB were studied, including noncirrhotic patients without HCC (N = 234), cirrhotic patients without (N = 281) and with HCC (N = 434). Patients were genotyped for 10 candidate single nucleotide polymorphisms (SNPs) by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. RESULTS: By multivariate logistic regression analysis adjusted for Child-Pugh scores, noneffective antiviral treatment, drinking history, family history of HCC, and age >=50 years old were associated with HCC risk (odds ratio [OR] = 5.923, 2.456, 2.241, 1.955, respectively). Sixty-two of 170 cirrhotic patients who achieved sustained virological suppression by antiviral treatment developed HCC, with fatty liver disease, family history of HCC, and family history of hepatitis B virus (HBV) infection as the risk factors (OR = 11.646, 3.339, 2.537, respectively). The SNPs associated with HCC risk in patients with cirrhosis and CHB were rs11536889 in TLR4 and rs2853744 in SPP1. Polymorphisms of TLR4 rs2149356, AP3S2 rs2290351, STXBP5L rs2169302, MLEC rs7976497, and SOCS3 rs4969168 were associated with HCC risk in specific stratified analyses with gender, age, and drinking history in the cirrhotic patients. CONCLUSIONS: Inadequate antiviral treatment, family history of HCC, drinking history, and age >=50 years old are risk factors for HCC. Sustained suppression of HBV does not eliminate the risk of HCC. Specific host genetic factors may impact HCC development in Han Chinese cirrhotic patients with CHB, including SNPs in TLR4, SPP1, AP3S2, STXBP5L, MLEC, and SOCS3, which warrant further validation in additional cohorts. PMID- 27391585 TI - Kinetic and thermodynamic studies of sulforaphane adsorption on macroporous resin. AB - The adsorption equilibrium, kinetic and thermodynamic of sulforaphane (SF) adsorption onto macroporous resin in aqueous phase were studied. The SP850 resin was screened as the appropriate resin for SF purification. From the equilibrium studies, the Redlich-Peterson model was found to be the best for description of the adsorption behavior of SF onto SP850 resin, followed by the Freundlich model and the Langmuir model. Batch equilibrium experiments demonstrated that, in the examined temperature range, the equilibrium adsorption capacity of SP850 resin decreased with increasing adsorption temperature. Thermodynamics studies indicated that the adsorption of SF was a physical, exothermic, and spontaneous process. The adsorption kinetics revealed that the pseudo-second-order kinetic model was suitable to characterize the kinetics of adsorption of SF onto SP850. Finally, the intra-particle diffusion model demonstrated that SF diffused quickly into macropores, and that diffusion slowed down in the meso- and micropores. PMID- 27391587 TI - Correction: The Antsy Social Network: Determinants of Nest Structure and Arrangement in Asian Weaver Ants. AB - [This corrects the article DOI: 10.1371/journal.pone.0156681.]. PMID- 27391586 TI - Comorbid symptoms of emotional distress in adult survivors of childhood cancer. AB - BACKGROUND: Childhood cancer survivors are at risk for emotional distress symptoms, but symptom comorbidity has not been previously examined. This study examined distress profiles for adult survivors of childhood cancer diagnosed between 1970 and 1999. METHODS: Self-reported depression, anxiety, and somatization symptoms from Brief Symptom Inventory 18 were examined in survivors (n = 16,079) and siblings (n = 3085) from the Childhood Cancer Survivor Study. A latent profile analysis identified clusters of survivors with individual and comorbid symptoms. Disease, treatment, and demographic predictors of distress comorbidity patterns were examined with multinomial logistic regressions. RESULTS: Four clinically relevant profiles were identified: low distress on all subscales (asymptomatic, 62%), high distress on all subscales (comorbid distress, 11%), elevated somatization (somatic symptoms, 13%), and elevated depression and anxiety (affective distress, 14%). Compared with siblings, fewer survivors were asymptomatic (62% vs 74%, P < .0001), and more had comorbid distress (11% vs 5%, P < .0001). Survivors of leukemia (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.12-1.61), central nervous system tumors (OR, 1.30; 95% CI, 1.05-1.61), and sarcoma (OR, 1.26; 95% CI, 1.01-1.57) had a greater risk of comorbid distress than survivors of solid tumors. Psychoactive medications were associated with comorbid distress (P < .0001), and this suggested that this group was refractory to traditional medical management. Comorbid distress was associated with poor perceived health (OR, 31.7; 95% CI, 23.1-43.3), headaches (OR, 3.2; 95% CI, 2.8 3.7), and bodily pain (OR, 4.0; 95% CI, 3.2-5.0). CONCLUSIONS: A significant proportion of survivors are at risk for comorbid distress, which may require extensive treatment approaches beyond those used for individual symptoms. Cancer 2016;122:3215-24. (c) 2016 American Cancer Society. PMID- 27391588 TI - Use of the Electronic Medical Record to Assess Pancreas Size in Type 1 Diabetes. AB - AIMS: This study harnessed the electronic medical record to assess pancreas volume in patients with type 1 diabetes (T1D) and matched controls to determine whether pancreas volume is altered in T1D and identify covariates that influence pancreas volume. METHODS: This study included 25 patients with T1D and 25 age-, sex-, and weight-matched controls from the Vanderbilt University Medical Center enterprise data warehouse. Measurements of pancreas volume were made from medical imaging studies using magnetic resonance imaging (MRI) or computed tomography (CT). RESULTS: Patients with T1D had a pancreas volume 47% smaller than matched controls (41.16 ml vs. 77.77 ml, P < 0.0001) as well as pancreas volume normalized by subject body weight, body mass index, or body surface area (all P < 0.0001). Pancreatic volume was smaller with a longer duration of T1D across the patient population (N = 25, P = 0.04). Additionally, four individual patients receiving multiple imaging scans displayed progressive declines in pancreas volume over time (~ 6% of volume/year), whereas five controls scanned a year apart did not exhibit a decline in pancreas size (P = 0.03). The pancreas was uniformly smaller on the right and left side of the abdomen. CONCLUSIONS: Pancreas volume declines with disease duration in patients with T1D, suggesting a protracted pathological process that may include the exocrine pancreas. PMID- 27391589 TI - Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats. AB - The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP). Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats. PMID- 27391591 TI - Phosphoinositide-binding proteins in autophagy. AB - Phosphoinositides represent a very small fraction of membrane phospholipids, having fast turnover rates and unique subcellular distributions, which make them perfect for initiating local temporal effects. Seven different phosphoinositide species are generated through reversible phosphorylation of the inositol ring of phosphatidylinositol (PtdIns). The negative charge generated by the phosphates provides specificity for interaction with various protein domains that commonly contain a cluster of basic residues. Examples of domains that bind phosphoinositides include PH domains, WD40 repeats, PX domains, and FYVE domains. Such domains often display specificity toward a certain species or subset of phosphoinositides. Here we will review the current literature of different phosphoinositide-binding proteins involved in autophagy. PMID- 27391590 TI - Implementation of recommended type 2 diabetes care for people with severe mental illness - a qualitative exploration with healthcare professionals. AB - BACKGROUND: The purpose of this study was to explore the barriers and facilitators healthcare professionals experience when managing type 2 diabetes in people with severe mental illness (SMI). METHODS: A qualitative semi-structured interview approach was employed. Questions were structured according to the Theoretical Domains Framework (TDF), which outlines 14 domains that can act as barriers and facilitators to changing behaviour. Interviews were audio-recorded and transcribed verbatim. The data were coded according to the 14 domains of the TDF, belief statements were created within each domain and the most relevant belief statements within each domain identified through a consensus approach. Analyses were conducted by two researchers, and discrepancies agreed with a third researcher. RESULTS: Sixteen healthcare professionals, from a range of services, involved in the care of people with type 2 diabetes and SMI took part in an interview. Inter-rater reliability for each of the domains varied (25 %-74 %). All fourteen domains were deemed relevant, with 42 specific beliefs identified as important to the target behaviour. Participants identified having relevant knowledge and skills for diabetes management, prioritising this area of health, and reviewing health behaviours to develop action plans, as particularly important. At an organisational level, integrated care provision and shared information technology (IT) services between mental health and physical services, and clearly defined roles and responsibilities for the different professions, with designated time to undertake the work were identified as crucial. CONCLUSIONS: The findings highlight that healthcare professionals' experience a range of barriers and enablers when attempting to manage type 2 diabetes in people with SMI. These include organisational factors and individual beliefs, suggesting that interventions need to be targeted at both an organisation and individual level in order to change behaviour. Further work is needed to model these relationships in a larger sample of participants in line with the MRC guidance for developing complex interventions. PMID- 27391592 TI - Impact of Soil Salinity on the Structure of the Bacterial Endophytic Community Identified from the Roots of Caliph Medic (Medicago truncatula). AB - In addition to being a forage crop, Caliph medic (Medicago truncatula) is also a model legume plant and is used for research focusing on the molecular characterization of the interaction between rhizobia and plants. However, the endophytic microbiome in this plant is poorly defined. Endophytic bacteria play a role in supplying plants with the basic requirements necessary for growth and development. Moreover, these bacteria also play a role in the mechanism of salinity stress adaptation in plants. As a prelude to the isolation and utilization of these bacteria in Caliph medic farming, 41 bacterial OTUs were identified in this project from within the interior of the roots of this plant by pyrosequencing of the small ribosomal subunit gene (16S rDNA) using a cultivation independent approach. In addition, the differential abundance of these bacteria was studied following exposure of the plants to salinity stress. About 29,064 high-quality reads were obtained from the sequencing of six libraries prepared from control and salinity-treated tissues. Statistical analysis revealed that the abundance of ~70% of the OTUs was significantly (p <= 0.05) altered in roots that were exposed to salinity stress. Sequence analysis showed a similarity between some of the identified species and other, known, growth-promoting bacteria, marine and salt-stressed soil-borne bacteria, and nitrogen-fixing bacterial isolates. Determination of the amendments to the bacterial community due to salinity stress in Caliph medic provides a crucial step toward developing an understanding of the association of these endophytes, under salt stress conditions, in this model plant. To provide direct evidence regarding their growth promoting activity, a group of endophytic bacteria were isolated from inside of plant roots using a cultivation-dependent approach. Several of these isolates were able to produce ACC-deaminase, ammonia and IAA; and to solubilize Zn+2 and PO4-3. This data is consistent with the predicted occurrence (based on cultivation-independent techniques) of these bacteria and provides some insight into the importance of the endophytic bacteria in Caliph medic when grown under normal and saline conditions. PMID- 27391593 TI - Introgression of opaque2 into Waxy Maize Causes Extensive Biochemical and Proteomic Changes in Endosperm. AB - Waxy maize is prevalently grown in China and other countries due to the excellent characters and economic value. However, its low content of lysine can't meet the nutritional requirements of humans and livestock. In the present study, we introgressed the opaque2 (o2) allele into waxy maize line Zhao OP-6/O2O2 by using marker-assisted selection (MAS) technique and successfully improved the lysine content and quality of waxy maize. Transcript abundance analysis indicated that the wx1 expression levels had no difference between Zhao OP-6/o2o2 and Zhao OP 6/O2O2. However, Zhao OP-6/o2o2 was characterized by a phenotype of hard and vitreous kernels and accumulation of protein bodies at smaller size (one third of that of parents) but in larger numbers. Biochemical analyses showed that Zhao OP 6/o2o2 had 16.7% less free amino acids than Zhao OP-6/O2O2, especially those derived from glycolytic intermediates, but its content of lysine was increased by 51.6% (0.47% vs. 0.31%). The content of amylopectin was 98.5% in Zhao OP-6/o2o2, significantly higher than that in Zhao OP-6/O2O2 (97.7%). Proteomic analyses indicated that o2 introgression not only decreased the accumulation of various zein proteins except for 27-kDa gamma-zein, but also affected other endosperm proteins related to amino acid biosynthesis, starch-protein balance, stress response and signal transduction. This study gives us an intriguing insight into the metabolism changes in endosperm of waxy maize introgressed with opaque2. PMID- 27391594 TI - Health Worker Compliance with a 'Test And Treat' Malaria Case Management Protocol in Papua New Guinea. AB - The Papua New Guinea (PNG) Department of Health introduced a 'test and treat' malaria case management protocol in 2011. This study assesses health worker compliance with the test and treat protocol on a wide range of measures, examines self-reported barriers to health worker compliance as well as health worker attitudes towards the test and treat protocol. Data were collected by cross sectional survey conducted in randomly selected primary health care facilities in 2012 and repeated in 2014. The combined survey data included passive observation of current or recently febrile patients (N = 771) and interviewer administered questionnaires completed with health workers (N = 265). Across the two surveys, 77.6% of patients were tested for malaria infection by rapid diagnostic test (RDT) or microscopy, 65.6% of confirmed malaria cases were prescribed the correct antimalarials and 15.3% of febrile patients who tested negative for malaria infection were incorrectly prescribed an antimalarial. Overall compliance with a strictly defined test and treat protocol was 62.8%. A reluctance to test current/recently febrile patients for malaria infection by RDT or microscopy in the absence of acute malaria symptoms, reserving recommended antimalarials for confirmed malaria cases only and choosing to clinically diagnose a malaria infection, despite a negative RDT result were the most frequently reported barriers to protocol compliance. Attitudinal support for the test and treat protocol, as assessed by a nine-item measure, improved across time. In conclusion, health worker compliance with the full test and treat malaria protocol requires improvement in PNG and additional health worker support will likely be required to achieve this. The broader evidence base would suggest any such support should be delivered over a longer period of time, be multi dimensional and multi-modal. PMID- 27391595 TI - PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes. AB - Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease. PMID- 27391596 TI - Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene. AB - BACKGROUND: Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations. METHODS AND RESULTS: Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment. CONCLUSIONS: We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures. PMID- 27391597 TI - Detection of airbag impact-induced cone photoreceptor damage by adaptive optics scanning laser ophthalmoscopy: a case report. AB - BACKGROUND: The purpose of this study was to report a case of traumatic maculopathy with para-central visual field defects following an impact by airbag deployment using adaptive optics scanning laser ophthalmoscopy (AO-SLO). CASE PRESENTATION: A 51-year-old man was involved in a motor vehicular accident and his left eye was struck by the deployed airbag, resulting in a para-central scotoma. The patient underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with prototype AO-SLO systems (Canon Inc.) at 14 and 22 months after the injury. Images focused on the photoreceptor layer were recorded in the foveal area, and a montage of AO-SLO images was created. On AO-SLO, focal dark areas could be observed in the left eye at 14 months after the injury. The analysis showed that the cone mosaic (cone density, 16503/mm(2); ratio of hexagonal Voronoi domain, 36.3 %; average nearest neighbor distance (NND)/expected NND, 0.606) was disordered compared with the normal area of the same eye (cone density, 24821/mm(2); ratio of hexagonal Voronoi domain, 44.1 %; average NND/expected NND, 0.739). The cone defect area corresponded to the area of the scotoma. A second AO-SLO was performed on the patient at 22 months after the injury and although there were still areas with reduced cone reflectivity, partial improvement of cone mosaic was detected by AO SLO at this time point. CONCLUSION: Partial recovery of damaged cone photoreceptors following closed globe blunt ocular trauma can be documented using AO-SLO longitudinal tracking. PMID- 27391598 TI - "New" metastases are associated with a poorer prognosis than growth of pre existing metastases in patients with metastatic breast cancer treated with chemotherapy. AB - INTRODUCTION: Progression-free survival (PFS) and overall survival (OS) endpoints often only weakly correlate. This analysis investigates how different progression events impact on OS, using data from two phase 3 studies with eribulin in women with advanced/metastatic breast cancer (MBC). METHODS: In Study 301, 1102 women with <=2 prior chemotherapies for advanced/MBC were randomized to eribulin mesylate (1.4 mg/m(2) on days 1 and 8 every 21 days) or capecitabine (1.25 g/m(2) twice daily on days 1-14 every 21 days). Study 305/EMBRACE enrolled 762 patients following two to five prior chemotherapies for advanced/MBC, randomized to eribulin (as above) or treatment of physician's choice. We analyzed OS and PFS post hoc for patients whose disease progressed due to development of "new" metastases, growth of pre-existing lesions, and patients with no reported disease progression. RESULTS: In both clinical studies, development of new metastases was associated with an increased risk of death (p < 0.0001). The time to development of new metastasis or death was significantly longer with eribulin than the comparator in Study 305 (p = 0.0017), but not in Study 301 (p = 0.46). Significantly longer OS was observed in the eribulin compared with the comparator arm for the new metastases subgroup in Study 301 (p = 0.008), but not in Study 305 (p = 0.16), compared with other progression subgroups. CONCLUSIONS: Patients with MBC progressing with new metastases have a worse prognosis than those whose disease progresses due to growth of existing lesions or patients with no reported disease progression. These findings have potentially important implications for the interpretation of clinical study data and clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov registration IDs: Study 301: NCT00337103 ; Study 305: NCT00388726 . PMID- 27391599 TI - Methodological issues on the use of administrative data in healthcare research: the case of heart failure hospitalizations in Lombardy region, 2000 to 2012. AB - BACKGROUND: Administrative data are increasingly used in healthcare research. However, in order to avoid biases, their use requires careful study planning. This paper describes the methodological principles and criteria used in a study on epidemiology, outcomes and process of care of patients hospitalized for heart failure (HF) in the largest Italian Region, from 2000 to 2012. METHODS: Data were extracted from the administrative data warehouse of the healthcare system of Lombardy, Italy. Hospital discharge forms with HF-related diagnosis codes were the basis for identifying HF hospitalizations as clinical events, or episodes. In patients experiencing at least one HF event, hospitalizations for any cause, outpatient services utilization, and drug prescriptions were also analyzed. RESULTS: Seven hundred one thousand, seven hundred one heart failure events involving 371,766 patients were recorded from 2000 to 2012. Once all the healthcare services provided to these patients after the first HF event had been joined together, the study database totalled about 91 million records. Principles, criteria and tips utilized in order to minimize errors and characterize some relevant subgroups are described. CONCLUSIONS: The methodology of this study could represent the basis for future research and could be applied in similar studies concerning epidemiology, trend analysis, and healthcare resources utilization. PMID- 27391600 TI - Antioxidant activities and oxidative stress inhibitory effects of ethanol extracts from Cornus officinalis on raw 264.7 cells. AB - BACKGROUND: Cornus officinalis, is a deciduous tree native to the eastern Asia, distributes mainly in (e.g. Korea, as well as China, and Japan). It is used as folk medicine to backache, polyuria, hypertension and nervous breakdown. Pharmacological studies have demonstrated that C. officinalis possess anti oxidant, anti-hyperglycemic, and immune regulatory effects. However, reports on the antioxidant activity of C. officinalis have been limited to in vitro radical scavenging studies. Its mechanism of action within the cell at the genetic level especially has not yet been clearly defined. Therefore, we investigated the anti antioxidant activities of C. officinalis in RAW 264.7 cells. METHODS: The antioxidant activities and protective effects of C. officinalis ethanol extract on cell damage and the antioxidant enzyme system in lipopolysaccharide (LPS) induced oxidative stress-damaged RAW 264.7 cells were assessed. To measure the effects of C. officinalis on antioxidant activities, we used the following methods: Total phenol and flavonoid contents, DPPH scavenging activity assay, ABTS scavenging activity assay, FRAP value measurement, xanthine oxidase activity assay, ROS generation measurement and real time PCR. RESULTS: The total phenol and flavonoid contents of C. officinalis extracts were 27.04 mg GAE/g and 3.70 mg QE/g, respectively. The antioxidant activities of C. officinalis extracts increased in a dose-dependent manner: the IC50 values for DPPH and ABTS radical scavenging activities of C. officinalis extracts were 99.32 MUg/mL and 138.51 MUg/mL, respectively. C. officinalis extracts inhibited xanthine oxidase activity and reactive oxygen species generation. The expression of antioxidant enzymes, Cu/ZnSOD, MnSOD, catalase, and glutathione peroxidase increased upon treatment with C. officinalis extracts at 100 MUg/mL, compared to that in the LPS-treated group. CONCLUSIONS: These results suggest the therapeutic potential of C. officinalis extract as an anti-oxidant agent. PMID- 27391601 TI - The cost-effectiveness challenge: is it worth it? AB - Scarcity of resources means that difficult choices have to be made about how to use them. Cost-effectiveness evidence provides a way to help decision-makers get 'best value' from their resources when choosing between two or more clinical or other interventions. Often it is found that one intervention has better outcomes than another, but also costs more. In these circumstances there is a need for the decision-maker to reach a view as to whether those better outcomes are 'worth' the higher costs, necessitating difficult trade-offs. Illustrations from the dementia field are given to illustrate how these trade-offs might be made. For strategic decisions it has often proved helpful to use a generic outcome measure such as the quality-adjusted life year. The fundamental aim of a healthcare system is not to save money, but to save and improve lives. Cost-effectiveness and similar analyses can help by showing how to get the most out of available resources. PMID- 27391602 TI - Cloning and rescue of the genome of Bombyx mori bidensovirus, and characterization of a recombinant virus. AB - BACKGROUND: Bombyx mori bidensovirus (BmBDV), which belongs to the Bidnaviridae family established by the International Committee on Taxonomy of Viruses in 2011, was the first bidensovirus identified in insects. The structure of BmBDV is similar to that of parvoviruses, while its replication is similar to that of adenoviruses. Although BmBDV has the potential to be used as a tool in biological pest control and as an expression vector, virus rescue has been a bottleneck in the application of this virus. METHODS: In this study, we constructed a full length genomic clone of BmBDV and showed that its terminal structure was restored. A recombinant BmBDV that expressed the green fluorescence protein (GFP) gene was constructed. Then, BmN cells, which are an ovarian cell line, were co transfected with the linearized genome using continuous culture and expanded cell culture methods. RESULTS: The results showed that the GFP gene was expressed successfully, and that cell lesions occurred in virus-infected cells. Furthermore, typical densonucleosis viruses were observed in reinfected silkworm larvae and larval midgut tissues infected by BmBDV, as evidenced by the emission of green fluorescence. CONCLUSIONS: Overall, these results suggest that the virus could be rescued from the infected BmN cells after co-transfection with the linear full length virus genome. PMID- 27391603 TI - Effects of Cationic Microbubble Carrying CD/TK Double Suicide Gene and alphaVbeta3 Integrin Antibody in Human Hepatocellular Carcinoma HepG2 Cells. AB - OBJECTIVE: Hepatocellular carcinoma (HCC), mostly derived from hepatitis or cirrhosisis, is one of the most common types of liver cancer. T-cell mediated immune response elicited by CD/TK double suicide gene has shown a substantial antitumor effect in HCC. Integrin alphaVbeta3 over expresssion has been suggested to regulate the biology behavior of HCC. In this study, we investigated the strategy of incorporating CD/TK double suicide gene and anti-alphaVbeta3 integrin monoclonal antibodies into cationic microbubbles (CMBsalphavbeta3), and evaluated its killing effect in HCC cells. METHODS: To improve the transfection efficiency of targeted CD/TK double suicide gene, we adopted cationic microbubbles (CMBs), a cationic delivery agent with enhanced DNA-carrying capacity. The ultrasound and high speed shearing method was used to prepare the non-targeting cationic microbubbles (CMBs). Using the biotin-avidin bridge method, alphaVbeta3 integrin antibody was conjugated to CMBs, and CMBsalphavbeta3 was generated to specifically target to HepG2 cells. The morphology and physicochemical properties of the CMBsalphavbeta3 was detected by optical microscope and zeta detector. The conjugation of plasmid and the antibody in CMBsalphavbeta3 were examined by immunofluorescent microscopy and flow cytometry. The binding capacities of CMBsalphavbeta3 and CMBs to HCC HepG2 and normal L-02 cells were compared using rosette formation assay. To detect EGFP fluorescence and examine the transfection efficiencies of CMBsalphavbeta3 and CMBs in HCC cells, fluorescence microscope and contrast-enhanced sonography were adopted. mRNA and protein level of CD/TK gene were detected by RT-PCR and Western blot, respectively. To evaluate the anti tumor effect of CMBsalphavbeta3, HCC cells with CMBsalphavbeta3 were exposed to 5 flurocytosine / ganciclovir (5-FC/GCV). Then, cell cycle distribution after treatment were detected by PI staining and flow cytometry. Apoptotic cells death were detected by optical microscope and assessed by MTT assay and TUNEL-staining assay. RESULTS: CMBsalphavbeta3 had a regular shape and good dispersion. Compared to CMBs, CMBsalphavbeta3 had more stable concentrations of alphaVbeta3 ligand and pEGFP-KDRP-CD/TK, and CMBsalphavbeta3 was much sticker to HepG2 HCC cells than normal liver L-02cells. Moreover, after exposed to anti-alphaVbeta3 monoclonal antibody, the adhesion of CMBsalphavbeta3 to HepG2 cells and L-02 cells were significantly reduced. Also, CMBsalphavbeta3 demonstrated a substantially higher efficiency in pEGFP-KDRP-CD/TK plasmid transfection in HepG2 cells than CMBs. In addition, CMBsalphavbeta3 could significantly facilitate 5-FC/GCV-induced cell cycle arrest in S phase. Moreover, treatment of 5-FC/GCV combined with CMBsalphavbeta3 resulted in a marked apoptotic cell death in HepG2 and SK-Herp-1 HCC cells. In vitro, treatment of 5-FC/GCV combined with CMBsalphavbeta3 suppresed cell proliferation. In nude mice model, 5-FU + GCV combined with plasmid + CMBsalphavbeta3were able to significantly suppress tumor volumes. CONCLUSION: Through biotin-avidin mediation system, CMBsalphavbeta3 were successfully generated to specifically target HCC HepG2 cells. More importantly, CMBsalphavbeta3 could significantly facilitate 5-FC/GCV-induced cell cycle arrest and apoptotic cell death in HepG2 cells. Our study demonstrated a potential strategy that could be translated clinically to improve liver tumor gene delivery. PMID- 27391604 TI - Detection and Quantification of Mycobacterium tuberculosis in the Sputum of Culture-Negative HIV-infected Pulmonary Tuberculosis Suspects: A Proof-of-Concept Study. AB - RATIONALE: Rapid diagnosis of pulmonary tuberculosis (TB) is critical for timely initiation of treatment and interruption of transmission. Yet, despite recent advances, many patients remain undiagnosed. Culture, usually considered the most sensitive diagnostic method, is sub-optimal for paucibacillary disease. METHODS: We evaluated the Totally Optimized PCR (TOP) TB assay, a new molecular test that we hypothesize is more sensitive than culture. After pre-clinical studies, we estimated TOP's per-patient sensitivity and specificity in a convenience sample of 261 HIV-infected pulmonary TB suspects enrolled into a TB diagnostic study in Mbarara, Uganda against MGIT culture, Xpert MTB/RIF and a composite reference standard. We validated results with a confirmatory PCR used for sequencing M. tuberculosis. MEASUREMENTS AND RESULTS: Using culture as reference, TOP had 100% sensitivity but 35% specificity. Against a composite reference standard, the sensitivity of culture (27%) and Xpert MTB/RIF (27%) was lower than TOP (99%), with similar specificity (100%, 98% and 87%, respectively). In unadjusted analyses, culture-negative/TOP-positive patients were more likely to be older (P<0.001), female (P<0.001), have salivary sputum (P = 0.05), sputum smear negative (P<0.001) and less advanced disease on chest radiograph (P = 0.05). M. tuberculosis genotypes identified in sputum by DNA sequencing exhibit differential growth in culture. CONCLUSIONS: These findings suggest that the TOP TB assay is accurately detecting M. tuberculosis DNA in the sputum of culture negative tuberculosis suspects. Our results require prospective validation with clinical outcomes. If the operating characteristics of the TOP assay are confirmed in future studies, it will be justified as a "TB rule out" test. PMID- 27391605 TI - Beyond Oncolytics: E1B55K-Deleted Adenovirus as a Vaccine Delivery Vector. AB - Type 5 human adenoviruses (Ad5) deleted of genes encoding the early region 1B 55 kDa (E1B55K) protein including Onyx-015 (dl1520) and H101 are best known for their oncolytic potential. As a vaccine vector the E1B55K deletion may allow for the insertion of a transgene nearly 1,000 base pairs larger than now possible. This has the potential of extending the application for which the vectors are clinically known. However, the immune priming ability of E1B55K-deleted vectors is unknown, undermining our ability to gauge their usefulness in vaccine applications. For this reason, we created an E1B55K-deleted Ad5 vector expressing full-length single chain HIVBaLgp120 attached to a flexible linker and the first two domains of rhesus CD4 (rhFLSC) in exchange for the E3 region. In cell-based experiments the E1B55K-deleted vector promoted higher levels of innate immune signals including chemokines, cytokines, and the NKG2D ligands MIC A/B compared to an E1B55K wild-type vector expressing the same immunogen. Based on these results we evaluated the immune priming ability of the E1B55K-deleted vector in mice. The E1B55K-deleted vector promoted similar levels of Ad5-, HIVgp120, and rhFLSC-specific cellular and humoral immune responses as the E1B55K wild-type vector. In pre-clinical HIV-vaccine studies the wild-type vector has been employed as part of a very effective prime-boost strategy. This study demonstrates that E1B55K-deleted adenoviruses may serve as effective vaccine delivery vectors. PMID- 27391607 TI - Diverse Aquatic Adaptations in Nothosaurus spp. (Sauropterygia)-Inferences from Humeral Histology and Microanatomy. AB - Mid-diaphyseal cortical bone tissue in humeri of Nothosaurus spp. consists of coarse parallel-fibered bone, finer and higher organized parallel-fibered bone, and lamellar bone. Vascular canals are mainly arranged longitudinally and radially in a dominantly radial system. Blood vessels are represented by simple vascular canals, incompletely lined primary osteons, and fully developed primary osteons. Nothosaurus spp. shows a variety of diaphyseal microanatomical patterns, ranging from thick to very thin-walled cortices. In the early Anisian (Lower Muschelkalk), small- and large-bodied Nothosaurus spp. generally exhibit bone mass increase (BMI). In the middle to late Anisian (Middle Muschelkalk) small bodied nothosaurs retain BMI whereas larger-bodied forms tend to show a decrease in bone mass (BMD). During the latest Anisian to early Ladinian (Upper Muschelkalk), small- and few large-bodied nothosaurs retain BMI, whereas the majority of large-bodied forms exhibit BMD. The stratigraphically youngest nothosaurs document five microanatomical categories, two of which are unique among marine amniotes: One consists of a very heterogeneously distributed spongy periosteal organization, the other of very thin-walled cortices. The functional significance of the two unique microanatomical specializations seen in large bodied nothosaurs is the reduction of bone mass, which minimizes inertia of the limbs, and thus saves energy during locomotion. Transitions between the various microanatomical categories are rather gradual. Our results suggest that small bodied Nothosaurus marchicus and other, not further assignable small-bodied nothosaurs seem to have been bound to near-shore, shallow marine environments throughout their evolution. Some large-bodied Nothosaurus spp. followed the same trend but others became more active swimmers and possibly inhabited open marine environments. The variety of microanatomical patterns may be related to taxonomic differences, developmental plasticity, and possibly sexual dimorphism. Humeral microanatomy documents the diversification of nothosaur species into different environments to avoid intraclade competition as well as competition with other marine reptiles. Nothosaur microanatomy indicates that knowledge of processes involved in secondary aquatic adaptation and their interaction are more complex than previously believed. PMID- 27391606 TI - Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts. AB - Myeloid neoplasms with ring sideroblasts are currently categorized within the myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the World Health Organization classification. Recent findings have identified that the presence of ring sideroblasts in these disorders has a unique molecular basis, i.e., the somatic mutation of SF3B1, a gene encoding a splicing factor. Mutations of SF3B1 occur in up to 90% of patients with refractory anaemia with unilineage dysplasia (RARS) and 70% of those with refractory cytopenia with multilineage dysplasia and ring sideroblasts or RARS associated with marked thrombocytosis. Experimental evidence has shown that mutant SF3B1 results in the abnormal splicing of several genes, primarily due to misrecognition of 3' splice sites. The resulting aberrant mRNAs undergo nonsense-mediated mRNA decay (NMD), resulting in haploinsufficiency of canonical transcripts and protein expression. In addition, it is also possible that NMD-insensitive aberrant transcripts are translated into proteins with altered function. Patients with MDS carrying the SF3B1 mutation show a homogeneous disease phenotype characterized by isolated erythroid dysplasia and mild dysplasia in granulocytic or megakaryocytic lineages, supporting the notion that the SF3B1 mutation identifies a distinct entity within MDS. The available evidence suggests that these findings may have relevant impact on the diagnosis, classification and management of patients with these neoplasms. PMID- 27391609 TI - Transforming Health Care Scheduling and Access: Getting to Now. PMID- 27391608 TI - The Reversal Effect and Its Mechanisms of Tetramethylpyrazine on Multidrug Resistance in Human Bladder Cancer. AB - Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR). To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (-)-Epigallocatechin gallate (EGCG) and Tetramethylpyrazine (TMP) to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM) resistant Pumc-91 cells (Pumc-91/ADM) were assessed by Cell Counting Kit-8 (CCK 8) cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc 91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer chemotherapy. PMID- 27391610 TI - Healing the Wounds After the Fight: Army Medical Care to Repatriated Captives, Part I. PMID- 27391611 TI - 39-Year-Old Woman With Right Shoulder Pain. PMID- 27391612 TI - International Service Learning: Process for Training and Initiatives. PMID- 27391613 TI - From the Battlefield to the Bedside: Supporting Warfighter and Civilian Health With the "ART" of Whole Genome Sequencing for Antibiotic Resistance and Outbreak Investigations. AB - Awareness, responsiveness, and throughput characterize an approach for enhancing the clinical impact of whole genome sequencing for austere environments and for large geographically dispersed health systems. This Department of Defense approach is informing interagency efforts linking antibiograms of multidrug resistant organisms to their genome sequences in a public database. PMID- 27391614 TI - Removing Barriers in the Assessment of Combat-Related Post-traumatic Stress Disorder. AB - While the Veterans Health Administration continues to treat Vietnam War Veterans, approximately two million service men and women have returned from Iraq and Afghanistan. However, our treatments can only be as effective as the quality of our clinical assessment. Disclosure of trauma is facilitated when the type of trauma is present in the sociocultural environment of patient and clinician. Topics that once were deemed too shameful for inquiry, specifically, childhood abuse, domestic violence, sexual abuse, and military sexual trauma are now part of a standard assessment. Similarly, the standard clinical assessment of combat Veterans should include specific queries that address the darkest underside of wartime experiences. PMID- 27391616 TI - Reliability of the Deployment Resiliency Assessment. AB - This article describes the reliability of the instruments embedded in a mental health screening instrument designed to detect risky drinking, depression, and post-traumatic stress disorder among members of the Armed Forces. The instruments were generally reliable, however, the risky drinking screen (Alcohol Use Disorders Identification Test-Consumption) had unacceptable reliability (alpha = 0.58). This was the first attempt to assess psychometric properties of a screening and assessment instrument widely used for members of the Armed Forces. PMID- 27391615 TI - Is High-Intensity Functional Training (HIFT)/CrossFit Safe for Military Fitness Training? AB - High-intensity functional training (HIFT) is a promising fitness paradigm that gained popularity among military populations. Rather than biasing workouts toward maximizing fitness domains such as aerobic endurance, HIFT workouts are designed to promote general physical preparedness. HIFT programs have proliferated as a result of concerns about the relevance of traditional physical training (PT), which historically focused on aerobic condition via running. Other concerns about traditional PT include: (1) the relevance of service fitness tests given current combat demands, (2) the perception that military PT is geared toward passing service fitness tests, and (3) that training for combat requires more than just aerobic endurance. Despite its' popularity in the military, concerns have been raised about HIFT's injury potential, leading to some approaches being labeled as "extreme conditioning programs" by several military and civilian experts. Given HIFT programs' popularity in the military and concerns about injury, a review of data on HIFT injury potential is needed to inform military policy. The purpose of this review is to: (1) provide an overview of scientific methods used to appropriately compare injury rates among fitness activities and (2) evaluate scientific data regarding HIFT injury risk compared to traditional military PT and other accepted fitness activities. PMID- 27391617 TI - Associations Between Functional Movement Screening, the Y Balance Test, and Injuries in Coast Guard Training. AB - Tests that have the ability to predict injuries in various military and athletic populations are important because of the role they could play in primary prevention. Functional Movement Screen (FMS) and Y Balance Tests (YBT) may provide this prognostic ability. This study examined the association between injuries and age, physical characteristics, FMS, and upper and lower body YBTs among Coast Guard Maritime Security Response Team (MSRT) candidates. Thirty-one male Coast Guard Maritime Security Response Team candidates were administered the 7 FMS tests and lower- and upper-body YBTs before their intense 2-month training course. Age, height, weight, and body mass index were also obtained. Physical training-related injuries were recorded during the course. Injury incidence was 41%. Older age and lower scores on either FMS or the upper-body YBT were associated with higher injury risk. Performance of the lower-body YBT was not associated with injury risk. This is the first investigation showing that lower scores on the upper-body YBT were associated with higher injury risk and is in consonance with previous investigations demonstrating associations between lower FMS scores and higher injury risk. Certain limitations need to be addressed. Future studies should determine if FMS and the YBTs have prognostic ability in other populations. PMID- 27391618 TI - Promoting Help Seeking Among Veteran Households: Associations Between Exposure to Multiple Types of Health Messages and Intentions to Utilize Related Public Health Hotlines. AB - This study presents preliminary evidence that exposure to different health campaigns enhance intentions to seek help from telephone hotlines among Veteran households. Data were collected from telephone surveys (N = 8,756) conducted with both Veteran (n = 3,904), and for comparison, non-Veteran households (n = 4,852). Cox proportional hazard models were used to identify associations between message exposure variables ("type" or "number") with a high intent to use different hotlines (e.g., suicide prevention, domestic violence). As the number of types of messages an individual was exposed to increased, reported high intent for hotline use also increased. This remained significant across hotline type and for both Veteran and non-Veterans households. Results underscore the need for further research on dissemination strategies of public messaging and their impact on health behavior among Veteran populations. PMID- 27391619 TI - Prevalence of Musculoskeletal Symptoms, Excessive Daytime Sleepiness, and Fatigue in the Crewmembers of a U.S. Navy Ship. AB - OBJECTIVES: We assessed the prevalence of, and association among, musculoskeletal (MSK) symptoms, reported sleep, daytime alertness, fatigue, and consumption of caffeinated beverages. METHODS: Crewmembers of a U.S. Navy aircraft carrier (N = 767) completed a survey pertaining to demographics, exercise frequency, sleep duration, caffeinated beverages consumption, daytime sleepiness, fatigue, and MSK symptoms occurrence. RESULTS: Participants reported 6.12 hours of sleep per day while at sea, 31.8% reported increased daytime sleepiness, whereas 9% reported elevated fatigue levels. The 12-month prevalence of MSK symptoms was 57.5%, and the 7-day prevalence was 44.4%. Approximately 20% reported that MSK symptoms prevented them from carrying out normal activities. The lower back (39.5%) and knees (33.6%) were the two body parts most frequently reported for MSK symptoms. Symptoms in lower back, knees, and ankles/feet had an increased impact on preventing crewmembers from carrying out daily activities. Symptomatic crewmembers were more likely to report elevated daytime sleepiness, increased fatigue level, shorter nighttime sleep duration, and consume more caffeinated beverages. CONCLUSION: MSK symptoms were frequent and frequently prevented crewmembers from carrying out their daily activities. From an occupational health perspective, interventions to optimize sleep hygiene in the naval environment should also address the impact of MSK symptoms as a confounding factor. PMID- 27391621 TI - Principal Component Analysis of the Suicide Opinion Questionnaire in a U.S. Military Sample of Marine Corps Non-Commissioned Officers. AB - Attitudes about suicide are important to examine among individuals within a specific setting, profession, and/or culture; if found to be condemnatory, such attitudes can be effectively modified with training. The Suicide Opinion Questionnaire (SOQ) is one of the most commonly used instruments for the measurement of attitudes toward suicide. The SOQ has not been tested in military populations and the measure has demonstrated multiple different factor structures across various studies performed on civilian samples. The purpose of this study was twofold: (1) to gain an understanding of the applicability and utility of the SOQ for the military; and (2) to examine the relationship among sex, education, prior exposure to suicide within one's military unit, and suicide opinions. A total of 1,758 Marine Non-Commissioned Officers (NCOs) completed the SOQ as part of a suicide program evaluation study. Results demonstrated a 4-component structure for the SOQ, accounting for approximately 30% of the total variance. Sex, education, and prior exposure to suicide within one's military unit were significantly related to suicide opinions. Recommendations are made for the development and empirical evaluation of a new and/or adapted, culturally sensitive suicide attitude measure for the military. PMID- 27391622 TI - CHAMP Symposium on Androgens, Anabolic Steroids, and Related Substances: What We Know and What We Need to Know. AB - The Consortium of Health and Military Performance hosted a symposium in April 2015 entitled "Androgens, Anabolic Steroids, and Related Substances: What We Know and What We Need to Know" in response to concerns from the field regarding Anabolic Androgenic Steroids use by U.S. service members. The symposium was attended by military and civilian subject-matter experts in sports medicine and anabolic steroids and was held at the United Service Organizations (Naval Support Activity Bethesda) in Bethesda, Maryland. The expert panel was charged to define the way ahead in terms of androgen use, education, research, relevant policies and guidelines, and other concerns with particular relevancy to Special Operations Forces. The conference concluded with the following recommendations on these several key issues (1) connecting with users, (2) education and intervention, (3) knowledge and research gaps, and (4) establishing an information clearinghouse and clinical repository. PMID- 27391623 TI - Hearing Loss in Israeli Air Force Aviators: Natural History and Risk Factors. AB - OBJECTIVE: To investigate the natural history of hearing loss (HL) in Israeli military aviators and its risk factors. METHODS: Audiometric results of aviators with available audiometry at ages 30 and 40 years, and up to their last available audiometry were retrieved. HL DEFINITION: pure-tone threshold (PTT) of 30 dB or higher in at least one frequency in at least one ear, moderate-to-severe (M-S) HL as PTT of 45 dB or higher, and suspected noise-induced HL (NIHL) as HL at 3 to 6 kHz. Potential risk factors for HL were assessed by the chi(2) test and logistic regression models. RESULTS: 298 aviators were included. Rates of HL increased with age, up to 57.5% at age 50. All M-S HL at age 50 years had clues on previous examinations, but new HL was observed in all ages. Age was found as a statistically significant risk factor, but aircraft type was not. Total flying hours were found to be an independent risk factor for suspected NIHL only. Self reported earplug use was not found to protect from HL, with methodological limitations. CONCLUSIONS: HL is prevalent in aviators. Age and total flying hours are risk factors, the latter probably only for NIHL, whereas aircraft type is not. PMID- 27391620 TI - Relations Between Cognitive Functioning and Alcohol Use, Craving, and Post Traumatic Stress: An Examination Among Trauma-Exposed Military Veterans With Alcohol Use Disorder. AB - Cognitive dysfunction is commonly observed among individuals with alcohol use disorder (AUD) and trauma exposure and is, in turn, associated with worse clinical outcomes. Accordingly, disruptions in cognitive functioning may be conceptualized as a trans-disease phenomenon representing a potential high-yield target for intervention. Less is known though about how different cognitive functions covary with alcohol use, craving, and post-traumatic stress symptom severity among trauma-exposed individuals with AUD. Sixty-eight male and female trauma-exposed military veterans with AUD, entering treatment trials to reduce alcohol use, completed measures assessing alcohol use and craving, post-traumatic stress symptom severity, and cognitive functioning. In multivariate models, after controlling for post-traumatic stress symptom severity, poorer learning and memory was associated with higher alcohol consumption and higher risk taking/impulsivity was associated with stronger preoccupations with alcohol and compulsions to drink. Alcohol consumption and craving, but not performance on cognitive tests, were positively associated with post-traumatic stress symptom severity. Findings suggest that interventions to strengthen cognitive functioning might be used as a preparatory step to augment treatments for AUD. Clinicians are encouraged to consider a standard assessment of cognitive functioning, in addition to post-traumatic stress symptom severity, in treatment planning and delivery for this vulnerable and high-risk population. PMID- 27391624 TI - Objectively Measured Physical Activity in Home Guard Soldiers During Military Service and Civilian Life. AB - Soldiers are encouraged to be physically active, and thereby maintain or increase their fitness level to meet job-related physical demands. However, studies on objectively measured physical activity (PA) in soldiers are scarce, particular for reserve soldiers. Hence, the aim of this study was to present PA data on Norwegian Home Guard (HG) soldiers. A total of 411 HG soldiers produced acceptable PA measurements (SenseWear Armband Pro2) during civilian life, of which 299 soldiers also produced acceptable data during HG military training. Reference data on total energy expenditure, metabolic equivalents, steps per day, and minutes of PA in three different metabolic equivalent categories are presented. The HG soldiers produced more minutes of moderate PA during HG military training compared to civilian life, but less vigorous and very vigorous PA. Furthermore, HG soldiers were more physically active during civilian week days compared to weekend days. The presented reference data can be used for comparisons against other groups of soldiers. Our data indicate that aerobic demands during HG military training were not very high. Promoting PA and exercise could still be important to ensure HG soldiers are physically prepared for more unforeseen job tasks. PMID- 27391625 TI - An Analysis of Personal Technology Use by Service Members and Military Behavioral Health Providers. AB - Personal technology use is ubiquitous in the United States today and technology, in general, continues to change the face of health care. However, little is known about the personal technology use of military service members and the behavioral health care providers that treat them. This study reports the technology use of 1,101 active duty service members and 45 behavioral health care providers at a large military installation. Participants reported Internet usage; ownership of smartphones, tablets, and e-readers; usage of mobile applications (apps); and basic demographic information. Compared with providers, service members reported higher rates of smartphone ownership, were more likely to own Android smartphones than iPhones, and spent more time gaming. Both groups spent a comparable amount of time using social media. With the exception of gaming, however, differences between service members and providers were not statistically significant when demographics were matched and controlled. Among service members, younger respondents (18-34) were statistically more likely than older respondents (35-58) to own smartphones, spend time gaming, and engage in social media. Our findings can help inform provider's technology-based education and intervention of their patients and guide the development of new technologies to support the psychological health of service members. PMID- 27391626 TI - Magnetic Field Interactions of Military and Law Enforcement Bullets at 1.5 and 3 Tesla. AB - OBJECTIVES: There are significant numbers of military and law enforcement bullets containing ferromagnetic materials. This study aimed to assess the magnetic field interactions for a representative sample of military and law enforcement ballistic objects at 1.5 and 3 tesla (T) to create a magnetic resonance imaging (MRI) compatibility database. METHODS: Twenty-nine different bullets underwent MRI evaluation. The deflection angle method and a qualitative torque scale were used. The samples were representative of those commonly used in the North Atlantic Treaty Organization (NATO) military forces (e.g., 5.56 mm NATO), law enforcement agencies (e.g., 9 mm Parabellum), and encountered in war injuries and crime-related trauma (e.g., 7.62 mm Kalashnikov). RESULTS: At all static magnetic field strengths, all non-nickel- and nonsteel-containing bullets exhibited no movement (deflection angle = 0 degrees ; torque = 0), whereas eight bullets containing steel core, steel jacket, or nickel jacket exhibited substantial magnetic field interactions over and above what might be regarded as safe in vivo (deflection angle = 90 degrees ; torque = 4+). CONCLUSION: Military and law enforcement non-nickel- or nonsteel-containing bullets appear to be safe for patients in MRI system at 1.5 and 3 T. On the other hand, nickel- and steel containing bullets exhibit movements that are considered potentially unsafe for patients in an MRI environment. PMID- 27391627 TI - Paul Revere and Forensic Dentistry. PMID- 27391628 TI - RE: When, If Ever, Should Military Physicians Violate a Military Order to Give Medical Obligations Higher Priority? PMID- 27391629 TI - RE: When, If Ever, Should Military Physicians Violate a Military Order to Give Medical Obligations Higher Priority? PMID- 27391630 TI - Challenges, Considerations, and Strategies in Hand Rejuvenation. AB - Hand rejuvenation is an increasingly requested procedure in dermatology. Dorsal hand augmentation with soft tissue filler is one aspect of hand rejuvenation. Calcium hydroxyapatite is FDA approved for this purpose, while at the present time other filler products are utilized but are considered off-label for dorsal hand augmentation. This article reviews the relevant anatomy, the general and filler-specific techniques commonly employed, and potential complications that may arise.

J Drugs Dermatol. 2016;15(7):809-815. PMID- 27391631 TI - Rituximab Use in Pediatric Dermatology. AB - Rituximab, an anti CD20 monoclonal antibody leading to transitory B cell depletion, is used to treat a wide variety of immune system tumors and immune mediated diseases. While most of data supporting the efficacy and safety of rituximab in treating autoimmune patients is focused on the adult population, the utilization of rituximab (RTX) for a wide range of pediatric conditions is also increasing. While there are a number of published case reports, a comprehensive review of the various uses for rituximab in pediatric dermatology is lacking. To better assess the therapeutic role of rituximab in the management of skin disease in children, here we comprehensively document reported cases of use including details regarding specific treatment regimens, efficacy and safety profile. Evaluation of the data supports consideration for the initiation of rituximab at early time points in the treatment ladder, before certain diseases become refractory to conventional treatment.

J Drugs Dermatol. 2016;15(7):821-829. PMID- 27391632 TI - Safety of Topical Dermatologic Medications in Pregnancy. AB - Dermatologic drugs should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Topical drugs have little systemic absorption. Therefore, they are deemed safer than oral or parenteral agents and less likely to harm the fetus. However, their safety profile must be assessed cautiously, as there is limited available data. In this article, we aggregate human and animal studies and provide recommendations on using topical dermatologic medications in pregnancy.

J Drugs Dermatol. 2016;15(7):830-834. PMID- 27391633 TI - Bensal HP Attenuates the Inflammatory Response in Hair Shaving Associated Dermatitis. AB - Shaving is an ubiquitous practice, and cutaneous irritation and inflammation are common sequelae, which may be worsened by underlying skin conditions or poor hair removal techniques. Moisturizing shaving creams and aftershaves are available to help maintain or restore the epidermal barrier; however, many continue to suffer from post-shave redness, itching, and pain. To reduce post-shave inflammation, some products have included botanical and other natural ingredients, which are often favored by consumers. We evaluated Bensal HP, an ointment containing 3% oak bark extract, 3% salicylic acid, and 6% benzoic acid, which has documented anti inflammatory and antimicrobial properties, in a murine model of shave irritation to determine whether it would be useful in this clinical setting. Shaving dermatitis was simulated using a depilatory agent and electric clippers, and the shaved area was photographed and treated with Bensal HP daily for four days. Compared to untreated controls, mice treated with Bensal HP experienced a visible reduction in skin irritation and inflammation. These findings were mirrored on histology, as Bensal HP-treated areas demonstrated increased epidermal integrity and decreased dermal inflammatory infiltrate compared to untreated skin. Using immunohistochemistry, fewer neutrophils and macrophages were noted, and cytokine analysis also revealed decreased IL-6 in Bensal HP-treated skin at 24 and 96 hours after shaving. These results highlight the potential of Bensal HP as an anti-inflammatory treatment for shave irritation. Given the product's application against a variety of inflammatory and infectious skin disorders, its use against shave irritation may also improve comorbid skin conditions, such as pseudofolliculitis barbae.

J Drugs Dermatol. 2016;15(7):836 840. PMID- 27391634 TI - Low-level Light Therapy for Treatment of Diabetic Foot Ulcer: A Review of Clinical Experiences. AB - BACKGROUND: Diabetic foot ulcers (DFU) represent a significant complication of diabetes mellitus (DM). DFU affect one in four patients with DM and treatments of DFU are limited and challenging. The management of DFU remains a significant healthcare and socioeconomic burden ($245 billion). There is a wide range of advanced therapies for DFU, but these are costly and have demonstrated only minimal efficacy in limited published studies. An emerging treatment modality to improve DFU and optimize wound healing is the use of low-level light therapy (LLLT). LLLT involves the use of light in the form of low-level or low-power laser or light emitting diodes to alter biochemical pathways, which may result in changes to cell shape, cell migration, and cell signaling.
OBJECTIVE: To review published clinical experiences (case series and case reports) using LLLT for treatment of DFU, and provide evidence-based recommendations and future directions on the potential of LLLT as a therapeutic modality for DFU.
METHODS AND MATERIALS: On January 16, 2016 we searched the published literature using databases: PubMed, EMBASE, CINAHL, and Web of Science with key terms: "diabetic foot" AND ("low level laser therapy" OR "low level light therapy" OR "LLLT" OR "light emitting diode" OR "phototherapy" OR "laser").
RESULTS: After screening of titles, abstracts and/or full-text, 7 original articles were suitable in our review. Our review contains 5 case series and 2 case reports that evaluated LLLT for treatment of DFU, and all reviewed studies have shown positive improvement of DFU using LLLT with no adverse events, albeit with limitations that may be minimized with future RCTs.
CONCLUSIONS: LLLT is an emerging and promising treatment modality to current alternatives that are costly and have shown limited success. Based upon the published evidence, we envision additional research may allow for stronger recommendation with LLLT for treatment of DFU.

J Drugs Dermatol. 2016;15(7):843-848. PMID- 27391635 TI - Topical Hemostatic-Anesthetic Solution to Reduce Bleeding During Mohs Micrographic Surgery: A Case Control Study. AB - BACKGROUND: Between stages of Mohs micrographic surgery, the wound is dressed and the patient waits for the histopathological results.
OBJECTIVE: To investigate the efficacy of a hemostatic-anesthetic solution-impregnated gauze in decreasing bleeding between Mohs stages.
MATERIALS AND METHODS: Twenty patients were treated with a hemostatic-anesthetic solution composed of tranexamic acid, adrenaline, and lidocaine (TAL), and 20 others were treated with a saline solution for control. At the second Mohs stage, size measurements of the blood stain on a Telfa pad and the defect were recorded. The Rotation Thromboelastometry Method (ROTEM) was used to investigate a possible effect of lidocaine and adrenaline on the clot stability induced by tranexamic acid.
RESULTS: The ratio of blood stain size to Mohs defect size in the hemostatic anesthetic solution group was 1:1.47, whereas the ratio in the control saline group was 1:3.37 (P<.001). Results of the ROTEM test showed that lidocaine and adrenaline did not interfere with the effect of tranexamic acid on clot formation and stability.
CONCLUSION: The application of gauze impregnated with tranexamic acid, adrenaline, and lidocaine on a surgical wound may be effective in reducing bleeding between Mohs stages.

J Drugs Dermatol. 2016;15(7):851-855. PMID- 27391636 TI - No Difference in Psychotropic Medication Use in Cosmetic and General Dermatology Patients. AB - BACKGROUND: Patients presenting for appearance-related concerns are often perceived as being more difficult (ie, more needy, more difficult to satisfy) than patients presenting for medical dermatologic problems. While the reasons for this perception are many, some hypothesize that this may be related to a higher rate of anxiety, depression, or body image issues among these patients.
OBJECTIVE: To determine the prevalence of psychotropic medication use in cosmetic dermatology patients compared to the prevalence of such medication use in general dermatology patients.
METHODS & MATERIALS: The study was a retrospective chart review of female patients, 18 or older, new to a private practice. Exclusion criteria included dermatologic disorders with known psychosocial comorbidity. Psychotropic medication use was recorded.
RESULTS: The percentage of subjects in the medical group (n=156) who reported using psychotropic medications was 22.2% compared to 26.8% in the cosmetic group (n=154; P=0.09).
CONCLUSION: The prevalence of psychotropic medication use among all dermatology patients in our practice was relatively high, but there was no statistically significant difference in the rate of psychotropic medication use in cosmetic dermatology patients compared to general dermatology patients.

J Drugs Dermatol. 2016;15(7):858-861. PMID- 27391637 TI - Efficacy and Tolerability of a Skin Brightening/Anti-Aging Cosmeceutical Containing Retinol 0.5%, Niacinamide, Hexylresorcinol, and Resveratrol. AB - Consumers are increasingly interested in over-the-counter skin care products that can improve the appearance of photodamaged and aging skin. This 10-week, open label, single- center study enrolled 25 subjects with mild to moderate hyperpigmentation and other clinical stigmata of cutaneous aging including fine lines, sallowness, lack of clarity, and wrinkling. Their mean age was 53.4+/-7.7 years. The test product contained retinol 0.5% in combination with niacinamide 4.4%, resveratrol 1%, and hexylresorcinol 1.1% in a moisturizing base. Subjects were provided a skin care regimen including a cleanser, hydrating serum, moisturizer, and an SPF 30 sunscreen for daily use. The test product was applied only at night.

The use of this skin brightening/anti-aging cosmeceutical was found to provide statistically significant improvements in all efficacy endpoints by study end. Fine lines, radiance, and smoothness were significantly improved as early as week 2 (P<.001). By week 4, hyperpigmentation, overall skin clarity, evenness of skin tone, and wrinkles showed statistically significant improvement compared to baseline. Mild retinoid dermatitis including flaking and redness occurred early in the study as reflected by tolerability scores. By week 10, subjects reported no stinging, itching, dryness, or tingling.

The results of this open-label clinical study suggest that a topical cream containing retinol 0.5% in combination with niacinamide, resveratrol, and hexylresorcinol is efficacious and tolerable for skin brightening/anti-aging when used with a complementary skin care regimen including SPF 30 sun protection.

J Drugs Dermatol. 2016;15(7):863-868. PMID- 27391638 TI - Differences in Cutaneous Irritation of Five Commonly Used Topical Products. AB - INTRODUCTION: Irritation, such as burning and stinging, on the site of application, is a common side effect of topical dermatologic products including creams, lotions, sprays, and foams. This effect may be more pronounced when applying products to atopic or psoriatic skin. The composition of the vehicle may affect the extent of the irritation. This study compared the irritation and erythema potential of 7 different topical dermatologic products to determine the products with the least likelihood of causing discomfort when applied.
METHODS: Seven sites on the anterior leg of 30 subjects were dry shaven with 10 upward strokes. Subjects rated the stinging of petrolatum (negative control), isopropyl alcohol (positive control), Cetaphil Lotion, triamcinolone 0.1% cream, triamcinolone 0.2% spray, betamethasone foam, and clobetasol 0.05% spray, 1 minute after product application, using a scale of 0 (no symptoms) to 10 (intolerable stinging/burning). The investigator assessed erythema at the sites 30 minutes after application of the products using a scale of 0 (none) to 4 (severe).
RESULTS: Stinging rating score of each product was statistically significant from one another. Petrolatum produced the least stinging (0) and isopropyl alcohol the most (10). Stinging with triamcinolone spray, Cetaphil Lotion, and triamcinolone cream ranked in the lower half of the rating scale (all below 5). Betamethasone foam and clobetal spray ranked the highest at >7. When corrected for the erythema caused by shaving, triamcinolone spray and Cetaphil Lotion produced the least amount of erythema of all the products tested.
DISCUSSION: Rapid evaporation of the volatile vehicle of triamcinolone spray and the non-irriating nature of the medication left behind may contribute to its low erythema and stinging. This product may be an appropriate choice for patients with compromised skin but who require the advantages and conveniences of a spray vehicle.

J Drugs Dermatol. 2016;15(7):870-873. PMID- 27391639 TI - A Phase III, Multicenter, Parallel-Design Clinical Trial to Compare the Efficacy and Safety of 5% Minoxidil Foam Versus Vehicle in Women With Female Pattern Hair Loss. AB - BACKGROUND Female pattern hair loss (FPHL) is a common hair disorder that affects millions of women. A new 5% minoxidil topical foam (MTF) formulation, which does not contain propylene glycol, has been developed.
OBJECTIVE: To compare the efficacy and safety of once-daily 5% MTF with vehicle foam for the treatment of FPHL.
MATERIALS AND METHODS: This was a Phase III, randomized, double-blind, vehicle-controlled, parallel-group, international multicenter trial (17 sites) in women aged at least 18 years with FPHL (grade D3 to D6 on the Savin Density Scale), treated once daily with 5% MTF or vehicle foam for 24 weeks. The co primary efficacy endpoints were the change from baseline at week 24 in target area hair count (TAHC) and subject assessment of scalp coverage. Also evaluated were TAHC at week 12, expert panel review of hair regrowth at week 24, and change from baseline in total unit area density (TUAD, sum of hair diameters/cm2) at weeks 12 and 24.
RESULTS: A total of 404 women were enrolled. At 12 and 24 weeks, 5% MTF treatment resulted in regrowth of 10.9 hairs/cm2 and 9.1 hairs/cm2 more than vehicle foam, respectively (both P<.0001). Improved scalp coverage at week 24 was observed by both subject self-assessment (0.69-point improvement over vehicle foam; P<.0001) and expert panel review (0.36-point improvement over the vehicle foam; P<.0001). TUAD increased by 658 μm/cm2 and 644 μm/cm2 more with 5% MTF than with vehicle foam at weeks 12 and 24, respectively (both P<.0001). MTF was well tolerated. A low incidence of scalp irritation and facial hypertrichosis was observed, with no clinically significant differences between groups.
CONCLUSION: Five percent MTF once daily for 24 weeks was well tolerated and promoted hair regrowth in women with FPHL, resulting in improved scalp coverage and increased hair density compared with vehicle foam. ClinicalTrials.gov identifier: nCT01226459

J Drugs Dermatol. 2016;15(7):874-881. PMID- 27391640 TI - Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator Blinded Study. AB - BACKGROUND: A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss.
OBJECTIVE: Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. METHODS: In a randomized, phase III trial, women with female pattern hair loss received once daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage.
RESULTS: Once-daily 5% MTF increased TAHC from baseline (adjusted mean +/- standard error) by 23.9 +/- 2.1 hairs/cm2 at week 24. Twice-daily 2% MTS increased TAHC 24.2 +/- 2.1 hairs/cm2 at week 24. The treatment difference was -0.3 hairs/cm2 (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated.
CONCLUSIONS: Once-daily 5% MTF and twice daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met.
ClinicalTrials.gov identifier: NCT01145625

J Drugs Dermatol. 2016;15(7):883-889. PMID- 27391641 TI - Effective Treatment of Xanthelasma. AB - Xanthelasma palpebrae are common lesions on both medical and dermatology patients. They are significant from both medical and dermatologic perspectives. They serve as a sentinel for elevated cholesterol as well as a cosmetic dermatologic issue. Treatment of these lesions requires consideration of diagnosing and treating any underlying cholesterol problem as well as removal of existing lesions. We report a simple yet effective method for treatment of these lesions.

J Drugs Dermatol. 2016;15(7):891-892. PMID- 27391642 TI - Loss of CD30 Expression in Anaplastic Large Cell Lymphoma Following Brentuximab Therapy. AB - Monoclonal antibody therapy is a new innovation in cancer therapy. Binding of monoclonal antibodies to tumor cells facilitates their destruction by the immune system. Tumor cells with mutated target antigens may escape detection by monoclonal antibodies and exhibit a selective growth advantage. This phenomenon was first recognized in CD20-negative B-cell lymphomas in patients previously treated with the anti-CD20 monoclonal antibody rituximab. We report a cutaneous recurrence of systemic ALCL with an anomalous CD30-negative immunophenotype. The patient had been previously treated with the anti-CD30 monoclonal antibody brentuximab. To our knowledge, we present the first reported case of a cutaneous recurrence of systemic ALCL with an anomalous CD30-negative immunophenotype following chronic brentuximab therapy.

J Drugs Dermatol. 2016;15(7):894-895. PMID- 27391643 TI - Aortic Endograft and Epithelioid Sarcoma: A Random Association or Causality? AB - BACKGROUND: Angiosarcoma is an uncommon, malignant neoplasm often found in skin and soft tissue. Epithelioid angiosarcoma (EA) is a rarer, more aggressive form of angiosarcoma most common in men in their seventh decade. Dacron(r), a polymer comprised of polyethylene terephthalate used in endografts for abdominal aortic aneurysm repairs, has been a suspected carcinogen associated with EA. Currently, three case reports exist in the literature purporting Dacron(r)-associated epithelioid angiosarcoma. Herein we report a case of Dacron(r)-associated EA.
CASE: A 64-year-old male with a recent history of a repaired type 2 endoleak and Dacron(r) endograft for his AAA presented with a painful skin eruption, fever, and weight loss. On exam, erythematous and violaceous papules and nodules were present on the patient's lower back. Biopsy revealed atypical, epithelioid cells forming vascular channels in a sheet-like and infiltrative pattern. These results and subsequent immunostaining were consistent with the diagnosis of EA. A bone marrow biopsy confirmed metastatic angiosarcoma.
CONCLUSION: This case further highlights Dacron(r) as a rare, but, potential carcinogen associated with EA.

J Drugs Dermatol. 2016;15(7):897-899. PMID- 27391644 TI - Association of anthropometric measures with kidney disease progression and mortality: a retrospective cohort study of pre-dialysis chronic kidney disease patients referred to a specialist renal service. AB - BACKGROUND: Although elevated body mass index (BMI) is a predictor of better clinical outcomes in dialysis patients, the evidence in pre-dialysis chronic kidney disease (CKD) is conflicting. Clinical measures of central obesity may be better prognostic indicators, although investigation has been limited. The aim of this study was to assess the predictive value of anthropometric measures for kidney failure progression and mortality in stage 3-4 CKD. METHODS: The study included newly referred stage 3-4 CKD patients at a single centre between 1/1/2008 and 31/12/2010. The associations between clinical measures of obesity (BMI, waist circumference [WC] and conicity index [ConI]) and time to a composite primary outcome of doubling of serum creatinine, commencement of renal replacement therapy or mortality were evaluated using the Kaplan-Meier method and multivariable Cox regression models. RESULTS: Over a median follow-up period of 3.3 years, 229 (25.4 %) patients of a total population of 903 experienced the composite primary renal outcome. When compared to normal BMI (18.5-24.9 kg/m(2), n = 174), the risk of the composite primary outcome was significantly lower in both the overweight (BMI 25-29.9 kg/m(2), n = 293; adjusted hazard ratio [HR] 0.50, 95 % CI 0.33-0.75) and obese class I/II groups (BMI 30-39.9 kg/m(2), n = 288; HR 0.62, 95 % CI 0.41-0.93), but not in the obese class III group (BMI >=40 kg/m(2), n = 72; HR 0.94, 95 % CI 0.52-1.69). All-cause mortality was also lower in the overweight group (HR 0.50, 95 % CI 0.30-0.83). WC and ConI were not associated with either the composite primary outcome or mortality. CONCLUSION: BMI in the overweight range is associated with reduced risks of kidney disease progression and all-cause mortality in stage 3-4 CKD. WC and ConI were not independent predictors of these outcomes in this population. PMID- 27391645 TI - Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction. AB - BACKGROUND: Microvascular injury (MVI) after coronary ischemia-reperfusion is associated with high morbidity and mortality. Both ischemia and reperfusion are involved in MVI, but to what degree these phases contribute is unknown. Understanding the etiology is essential for the development of new potential therapies. METHODS AND FINDINGS: Rats were divided into 3 groups receiving either 30 minutes ischemia, 90 minutes ischemia or 30 minutes ischemia followed by 60 minutes reperfusion. Subsequently hearts were ex-vivo perfused in a Langendorff model. Fluorescence and electron microscopy was used for analysis of capillary density, vascular permeability and ultrastructure. Most MVI was observed after 30 minutes ischemia followed by 60 minutes reperfusion. In comparison to the 30' and 90' ischemia group, wall thickness decreased (207.0+/-74 vs 407.8+/-75 and 407.5+/-71, p = 0.02). Endothelial nuclei in the 30'-60' group showed irreversible damage and decreased chromatin density variation (50.5+/-9.4, 35.4+/ 7.1 and 23.7+/-3.8, p = 0.03). Cell junction density was lowest in the 30'-60' group (0.15+/-0.02 vs 2.5+/-0.6 and 1.8+/-0.7, p<0.01). Microsphere extravasation was increased in both the 90' ischemia and 30'-60' group. CONCLUSIONS: Ischemia alone for 90 minutes induces mild morphological changes to the coronary microcirculation, with increased vascular permeability. Ischemia for 30 minutes, followed by 60 minutes of reperfusion, induces massive MVI. This shows the direct consequences of reperfusion on the coronary microcirculation. These data imply that a therapeutic window exists to protect the microcirculation directly upon coronary revascularization. PMID- 27391646 TI - Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort studya prospective cohort study. AB - BACKGROUND: Obstructive jaundice has been reported to influence liver elasticity, independent of liver fibrosis. The aim of our prospective study was to evaluate the changes in liver elasticity, before and after biliary drainage, in patients with obstructive jaundice, and to evaluate the correlation between elasticity measures and serum markers of liver fibrosis. METHODS: This is a prospective cohort study of 20 patients with obstructive jaundice. Liver elasticity was assessed by Transient Elastography (TE) and Virtual TouchTM Quantification (VTQ). Serum total bilirubin (T-Bil) level was measured before biliary drainage (Day 0), with measures repeated at 2 days (Day 2) and 7 days (Day 7) after biliary drainage. Serum levels of the following markers of liver fibrosis were also obtained on Day 0 and Day 7: hyaluronic acid (HA), procollagen-III-peptide (P-III P). RESULTS: T-Bil, TE, and VTQ for the left (VTQ-L) and right (VTQ-R) lobes of the liver were all elevated before biliary drainage, with respective levels, measured at Day 0, of 11.9 +/- 1.5 mg/dl, 12.1 +/- 0.9 kPa, 2.23 +/- 0.10 m/s, and 1.85 +/- 0.10 m/s. All values decreased on Day 7 after drainage: T-Bil, 4.7 +/- 1.0 mg/dl (P < 0.001); TE, 7.6 +/- 0.6 kPa (P < 0.001); VTQ-L, 1.53 +/- 0.08 m/s (P < 0.001); and VTQ-R, 1.30 +/- 0.05 m/s (P < 0.001). Similar changes were observed in serum markers of liver fibrosis. Liver elasticity measures correlated with serum levels of T-Bil, P-III-P, and HA (r = 0.35-0.67, P < 0.001). CONCLUSIONS: This study confirmed decreases in liver elasticity, measured by TE and VTQ, after biliary drainage. Measures of liver elasticity correlated to levels of T-Bil and serum markers of liver fibrosis. (UMIN ID: UMIN00001284313). TRIAL REGISTRATION: REGISTRATION NUMBER: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN00001284313 ); Registration date: 2014-01-14. PMID- 27391647 TI - Changes in Maternal Plasma Adiponectin from Late Pregnancy to the Postpartum Period According to the Mode of Delivery: Results from a Prospective Cohort in Rio de Janeiro, Brazil. AB - INTRODUCTION: Maternal plasma adiponectin is inversely related to insulin resistance, atherosclerosis and child health. However, little is known about its concentrations in the perinatal period, especially according to mode of delivery. Our aim is to evaluate the association between mode of delivery and changes in maternal plasma adiponectin from 3rd trimester of pregnancy to 30-45 days postpartum. METHODS: A cohort was recruited in Rio de Janeiro, Brazil, with four waves of follow-up: 5-13th, 22-26th, 30-36th gestational weeks and 30-45 days postpartum. Eligible subjects should be between 20-40 years of age, be free of chronic and infectious diseases and presenting with a singleton pregnancy. The mode of delivery was classified as vaginal (VD) or cesarean (CS). Plasma adiponectin concentration (MUg/mL) was measured using commercial ELISA kits. Statistical analyses included the Wilcoxon rank-sum test and the multiple linear mixed effects model. RESULTS: A total of 159 participated in the study. Median adiponectin concentrations were higher for the VD group (n = 99; 8.25, IQR: 5.85 11.90) than for the CS group (n = 60; 7.34, IQR: 4.36-9.76; p = 0.040) in the postpartum samples but were not different between the two groups in the 3rd trimester. Women who underwent CS had a lower rate of increase in adiponectin concentration from the 3rd trimester to 30-45 days postpartum compared to those who underwent VD (beta = -.15, 95% CI: -.28-.02, p = 0.030). CONCLUSION: The CS procedure was associated with lower maternal circulating concentrations of adiponectin at 30-45 days postpartum, compared to the VD. PMID- 27391648 TI - Puffy Skin Disease Is an Emerging Transmissible Condition in Rainbow Trout Oncorhynchus mykiss Walbaum. AB - The transmission of puffy skin disease (PSD) to rainbow trout Oncorhynchus mykiss Walbaum was tested in the laboratory by conducting co-habitation challenges with puffy skin (PS)-affected fish (Trojans) collected from the field. Two separate challenges were conducted using Trojans sourced from two different sites and diploid (first trial) or triploid (second trial) naive fish. PSD-specific clinical signs were observed in both groups of naive fish, with 66% of the fish sampled during the challenges showing signs of varying severity. The first clinical features of PSD were presented as white oval skin patches on one or both flanks 15-21 days post-challenge (dpc). The extent of the lesions ranged from 10 to 90% of the body surface, depending on the severity of the lesion. Both the severity and number of affected fish increased during the challenge. Macroscopically, oedema of the skin and multifocal petechial haemorrhaging were observed towards the end of the trials. Abnormal fish behaviour consisting of "flashing" and excessive mucous production was noted from 15 dpc onwards. Fish with severe PSD lesions also displayed inappetence and associated emaciation. Rodlet cells were observed in 41% of the fresh skin scrapes analysed from the second trial. Histologically epidermal oedema was observed in 31% of the naive fish showing gross pathology, with additional 12% displaying epidermal hyperplasia, mostly observed at the end of the challenge. Other concomitant features of the PSD lesions in challenged fish were epithelial erosion and sloughing, and occasionally mild or focal inflammation. No consistent pathology of internal organs was observed. The parasites Ichthyophthirius multifiliis and Ichthyobodo necator were observed in skin samples of a proportion of naive challenged fish and in Trojans but not in control fish. The presence of these and other known fish pathogens in the skin of PSD-fish was confirmed by high throughput sequencing analysis. In summary, we have demonstrated that PSD is a transmissible condition. However, even though a number of known fish pathogens were identified in the skin tissues of PSD-fish, the actual causative infectious agent(s) remain(s) unknown. PMID- 27391649 TI - Measuring Spatial Accessibility of Health Care Providers - Introduction of a Variable Distance Decay Function within the Floating Catchment Area (FCA) Method. AB - We integrated recent improvements within the floating catchment area (FCA) method family into an integrated 'iFCA'method. Within this method we focused on the distance decay function and its parameter. So far only distance decay functions with constant parameters have been applied. Therefore, we developed a variable distance decay function to be used within the FCA method. We were able to replace the impedance coefficient beta by readily available distribution parameter (i.e. median and standard deviation (SD)) within a logistic based distance decay function. Hence, the function is shaped individually for every single population location by the median and SD of all population-to-provider distances within a global catchment size. Theoretical application of the variable distance decay function showed conceptually sound results. Furthermore, the existence of effective variable catchment sizes defined by the asymptotic approach to zero of the distance decay function was revealed, satisfying the need for variable catchment sizes. The application of the iFCA method within an urban case study in Berlin (Germany) confirmed the theoretical fit of the suggested method. In summary, we introduced for the first time, a variable distance decay function within an integrated FCA method. This function accounts for individual travel behaviors determined by the distribution of providers. Additionally, the function inherits effective variable catchment sizes and therefore obviates the need for determining variable catchment sizes separately. PMID- 27391651 TI - Pinning Down the Reasons for the Size, Shape, and Stability of Nanobubbles. AB - A thermodynamic analysis of the size, shape, and stability of nanobubbles is carried out by modifying classical nucleation theory to include the supersaturation dependence of the surface tension. It is shown that the free energy of a nanobubble is a minimum at the critical radius when the contact line is pinned, that the size of the nanobubble is determined by the decrease in the surface tension caused by the degree of supersaturation, and that together these explain the increased exterior contact angle of a nanobubble compared with the corresponding angle of a macroscopic bubble or droplet on the same surface. PMID- 27391650 TI - Association of Anterior and Lateral Extraprostatic Extensions with Base-Positive Resection Margins in Prostate Cancer. AB - INTRODUCTION: Positive surgical margins (PSM) detected in the radical prostatectomy specimen increase the risk of biochemical recurrence (BCR). Still, with formidable number of patients never experiencing BCR in their life, the reason for this inconsistency has been attributed to the artifacts and to the spontaneous regression of micrometastatic site. To investigate the origin of margin positive cancers, we have looked into the influence of extraprostatic extension location on the resection margin positive site and its implications on BCR risk. MATERIALS & METHODS: The clinical information and follow-up data of 612 patients who had extraprostatic extension and positive surgical margin at the time of robot assisted radical prostatectomy (RARP) in the single center between 2005 and 2014 were modeled using Fine and Gray's competing risk regression analysis for BCR. Extraprostatic extensions were divided into categories according to location as apex, base, anterior, posterior, lateral, and posterolateral. Extraprostatic extensions were defined as presence of tumor beyond the borders of the gland in the posterior and posterolateral regions. Tumor admixed with periprostatic fat was additionally considered as having extraprostatic extension if capsule was vague in the anterior, apex, and base regions. Positive surgical margins were defined as the presence of tumor cells at the inked margin on the inspection under microscopy. Association of these classifications with the site of PSM was evaluated by Cohen's Kappa analysis for concordance and logistic regression for the odds of apical and base PSMs. RESULTS: Median follow-up duration was 36.5 months (interquartile range[IQR] 20.1 36.5). Apex involvement was found in 158 (25.8%) patients and base in 110 (18.0%) patients. PSMs generally were found to be associated with increased risk of BCR regardless of location, with BCR risk highest for base PSM (HR 1.94, 95% CI 1.40 2.68, p<0.001) after adjusting for age, initial prostate-specific antigen, pathologic Gleason score, and pathologic T stage in the multivariate model. Logistic regression for PSM site revealed no significant correlation of apex PSM with extraprostatic extension location, while base PSM was associated with increased odds of anterior (OR 2.513, 95% CI 1.425-4.430, p = 0.001) and lateral (OR 2.715, 95% CI 1.735-4.250, p<0.001) extraprostatic extension. CONCLUSION: Extension into the extraprostatic tissue on some specific locations do not share the same recur risk due to the different anatomical structures surrounding the organ. Anterior and lateral EPEs are prone to leave PSM on the base of the prostate, probably because of the lack of anatomical barricades slowing down the direct invasion process. More study on the pattern of spread of the tumors found to have extraprostatic extension is suggested for optimal planning of the operation extent and of the adjuvant radiotherapy. PMID- 27391652 TI - Correction to: Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis? PMID- 27391653 TI - Diagnosis and treatment of pediatric frontotemporal pits: report of 2 cases. AB - In contrast to more common nasal and cervical lesions, the frontotemporal pit is a rarely encountered lesion that is often associated with a dermoid and may track intracranially. Due to delays in diagnosis, the propensity to spread intracranially, and the risk of infection, awareness of these lesions and appropriate diagnosis and management are important. The authors present 2 cases of frontotemporal pits from a single institution. Epidemiology, presentation, and management recommendations are discussed. PMID- 27391654 TI - GCORE-sib: An efficient gene-gene interaction tool for genome-wide association studies based on discordant sib pairs. AB - BACKGROUND: A computationally efficient tool is required for a genome-wide gene gene interaction analysis that tests an extremely large number of single nucleotide polymorphism (SNP) interaction pairs in genome-wide association studies (GWAS). Current tools for GWAS interaction analysis are mainly developed for unrelated case-control samples. Relatively fewer tools for interaction analysis are available for complex disease studies with family-based design, and these tools tend to be computationally expensive. RESULTS: We developed a fast gene-gene interaction test, GCORE-sib, for discordant sib pairs and implemented the test into an efficient tool. We used simulations to demonstrate that the GCORE-sib has correct type I error rates and has comparable power to that of the regression-based interaction test. We also showed that the GCORE-sib can run more than 10 times faster than the regression-based test. Finally, the GCORE-sib was applied to a GWAS dataset with approximately 2,000 discordant sib pairs, and the GCORE-sib finished testing 19,368,078,382 pairs of SNPs within 6 days. CONCLUSIONS: An efficient gene-gene interaction tool for discordant sib pairs was developed. It will be very useful for genome-wide gene-gene interaction analysis in GWAS using discordant sib pairs. The tool can be downloaded for free at http://gcore-sib.sourceforge.net . PMID- 27391655 TI - Utility of Prophylactic Antibiotics in Nonoperative Facial Fractures. AB - Facial fractures are commonly managed nonoperatively. Patients with facial fractures involving sinus cavities commonly receive 7 to 10 days of prophylactic antibiotics, yet no literature exists to support or refute this practice. The aim of this study was to compare the administration and duration of antibiotic prophylaxis on the incidence of soft tissue infection in nonoperative facial fractures. A total number of 289 patients who were admitted to our level I trauma center with nonoperative facial fractures from the beginning of 2012 to the end of 2014 were studied. Patients were categorized into 3 groups: no antibiotic prophylaxis, short-term antibiotic prophylaxis (1-5 days), and long-term antibiotic prophylaxis (>5 days). The primary outcome was the incidence of facial soft tissue infection and Clostridium difficile colitis. Fifty patients received no antibiotic prophylaxis. Sixty-three patients completed a short course of antibiotic prophylaxis and 176 patients received long-term antibiotics. Ampicillin/sulbactam, amoxicillin/clavulanic acid, or a combination of both were used in 216 patients. Twenty-three patients received clindamycin due to penicillin allergy. Short and long courses of antibiotic prophylaxis were administered more commonly in patients with concomitant maxillary and orbital fractures (P <0.0001). No mortality was found in any group. Soft tissue infection was not identified in any patient. C. difficile colitis was identified in 1 patient who had received a long course of antibiotic prophylaxis (P = 0.7246). There was no difference in the outcome of patients receiving short-term, long term, and no antibiotic prophylaxis. Prospective randomized studies are needed to provide further clinical recommendations. PMID- 27391656 TI - Innervated Free Gracilis Muscle Transfer: An Experimental Model. AB - BACKGROUND: Although rodent models have been used extensively for surgical research, their use is limited in microsurgical tissue transfer due to their small size and the small size of their vessels and nerves. Also, fundamental anatomic differences may make rodent surgical models hard to extrapolate to humans. METHODS: In this report, the authors present a rabbit model for studying free tissue transfer and nerve regeneration using the innervated free gracilis muscle flap. In providing this report, the authors are hopeful that this model could become a standard investigative method for future investigators to employ in other translational endeavors. RESULTS: The authors have completed 12 innervated gracilis muscle transfers with 2 surgical site infections requiring antibiotic treatment and postoperative wound care. There were no complications related to flap-viability in the study over an average follow-up of 9 months. The return of muscle function with nerve coaptation is seen initially around 12 weeks and complete return of function occurs by 20 weeks. CONCLUSIONS: Rabbits are comparatively small, easily available, easy to handle, and cost-effective experimental models. Use of the innervated gracilis muscle free flap in rabbits can provide an excellent and economic model for free tissue transfer and reinnervation studies. PMID- 27391657 TI - Pediatric Craniofacial Fractures: Trajectories and Ramifications. AB - BACKGROUND: The pediatric craniofacial skeleton fractures in patterns distinct from those typical in adults; this has implications pertinent to management that may go unrecognized. The authors reviewed multilevel pediatric craniofacial fractures presenting to their institution, surmising that they would display an oblique trajectory of fracture patterns, and would be at increased risk of growing skull fractures (GSFs), compared with adults. METHODS: A retrospective review was performed of pediatric patients presenting with multilevel craniofacial fractures between 2004 and 2010. Demographics, cause of injury, fracture patterns, associated injuries, management, and follow-up information were gathered. Computed tomography scans were reviewed to characterize fracture length, displacement, and trajectory. Adverse outcomes were documented, with particular attention to GSFs. RESULTS: One hundred fifty-one patients met our inclusion criteria, which included a follow-up of >3 years. Average age at injury was 9.5 +/- 4.7 years. Patterns of fracture displayed near consistent obliquity, with only 4 patients (2.6%) displaying a LeFort-type facial fracture. LeFort patterns were associated with older patients over the age of 12, but without statistical significance (P = 0.07). Five patients (3.3%) died as a result of their injuries. 3.3% of patients developed a GSF. All craniofacial fracture patients demonstrated radiographic and/or clinical evidence of healed fractures at their last follow-up. CONCLUSIONS: This series of pediatric craniofacial fractures near consistently demonstrated oblique fracture patterns, in contrast to the typical adult fracture patterns described by LeFort. Pediatric craniofacial fractures are also at increased risk of GSFs. Understanding of these principles is fundamental to successful therapy in this population. PMID- 27391658 TI - Role of GATA-6 and Bone Morphogenetic Protein-2 in Dexamethasone-Induced Cleft Palate Formation in Institute of Cancer Research Mice. AB - The mechanism of cleft palate induction by dexamethasone is not fully known. Bone morphogenetic protein-2 (BMP-2) has been associated with dexamethasone-induced osteoporosis. In this study, the authors induced cleft palate models in Institute of Cancer Research mice by dexamethasone to investigate the role of BMP-2 and its transcriptional element GATA-6. The authors injected different doses of dexamethasone into pregnant mice (E13), and assessed the histology of the palatal shelf and the expression levels of BMP-2, GATA-6, and specific apoptosis-related proteins. The results showed that cleft palate formation was dependent on dexamethasone dosage, with high incidence (50.55%) at high concentration (50 mg/kg) compared with the low doses (6 mg/kg, 38.10%). Transmission electron microscopy revealed significant cellular changes of the cleft palate shelf, including loose cell connection, cellular swelling, as well as reduced extracellular matrix and mitochondria. Following exposure to dexamethasone, the apoptotic rate in the palate increased with elevated dosage. Western blotting analysis indicated that the expression levels of GATA-6 and BMP-2 were reduced, while the levels of apoptotic proteins bax and caspase-3 were increased. The results of authors' study suggested that dexamethasone-induced cleft palate formation involved apoptosis occurred in a dose-dependent manner. BMP-2 and GATA 6 mediated dexamethasone-induced cleft palate formation. PMID- 27391660 TI - Usefulness of an Osteotomy Template for Skull Tumorectomy and Simultaneous Skull Reconstruction. AB - BACKGROUND: Simultaneous tumor resection and cranioplasty with hydroxyapatite osteosynthesis are sometimes necessary in patients of skull neoplasms or skull invasive tumors. However, the disadvantage of simultaneous surgery is that mismatches often occur between the skull defect and the hydroxyapatite implant. To solve this problem, the authors developed a customized template for designing the craniotomy line. METHODS: Before each operation, the craniotomy design was discussed with a neurosurgeon. Based on the discussion, 2 hydroxyapatite implants were customized for each patient on the basis of models prepared using computed tomography data. The first implant was an onlay template for the preoperative cranium, which was customized for designing the osteotomy line. The other implant was used for the skull defect. Using the template, the osteotomy line was drawn along the template edge, osteotomy was performed along this line, and the implant was placed in the skull defect. RESULTS: This technique was performed in 3 patients. No implant or defect trimming was required in any patient, good cosmetic outcomes were noted in all patients, and no complications occurred. CONCLUSION: Use of predesigned hydroxyapatite templates for craniotomy during simultaneous skull tumor resection and cranioplasty has some clinical advantages: the precise craniotomy line can be designed, the implant and skull defect fit better and show effective osteoconduction, trimming of the implant or defect is minimized, and the operation time is shortened. PMID- 27391661 TI - Combined Scalp Flap and Cheek Flap in Large Cranial Defect. PMID- 27391664 TI - Introduction: Special Issue 'Translating and translations in the history of science'. PMID- 27391663 TI - The outcome of lumbar disc herniation surgery is worse in old adults than in young adults. AB - Background and purpose - The outcome of surgical treatment of lumbar disc herniation (LDH) has been thoroughly evaluated in middle-aged patients, but less so in elderly patients. Patients and methods - With validated patient-reported outcome measures (PROMs) and using SweSpine (the national Swedish Spine Surgery Register), we analyzed the preoperative clinical status of LDH patients and the 1 year postoperative outcome of LDH surgery performed over the period 2000-2012. We included 1,250 elderly patients (>= 65 years of age) and 12,840 young and middle aged patients (aged 20-64). Results - Generally speaking, elderly patients were referred for LDH surgery with worse PROM scores than young and middle-aged patients, they improved less by surgery, they experienced more complications, they had inferior 1-year postoperative PROM scores, and they were less satisfied with the outcome (with all differences being statistically significant). Interpretation - Elderly patients appear to have a worse postoperative outcome after LDH surgery than young and middle-aged patients, they are referred to surgery with inferior clinical status, and they improve less after the surgery. PMID- 27391665 TI - The letter, the dictionary and the laboratory: translating chemistry and mineralogy in eighteenth-century France. AB - Eighteenth-century scientific translation was not just a linguistic or intellectual affair. It included numerous material aspects requiring a social organization to marshal the indispensable human and non-human actors. Paratexts and actors' correspondences provide a good observatory to get information about aspects such as shipments and routes, processes of translation and language acquisition (dictionaries, grammars and other helpful materials, such as translated works in both languages), texts acquisition and dissemination (including author's additions and corrections, oral presentations in academic meetings and announcements of forthcoming translations). The nature of scientific translation changed in France during the second half of the eighteenth century. Beside solitary translators, it also happened to become a collective enterprise, dedicated to providing abridgements (Collection academique, 1755-79) or enriching the learned journals with full translations of the most recent foreign texts (Guyton de Morveau's 'Bureau de traduction de Dijon', devoted to chemistry and mineralogy, 1781-90). That new trend clearly had a decisive influence on the nature of the scientific press itself. A way to set up science as a social activity in the provincial capital of Dijon, translation required a local and international network for acquiring the linguistic and scientific expertise, along with the original texts, as quickly as possible. Laboratory results and mineralogical observations were used to compare material facts (colour, odour, shape of crystals, etc.) with those described in the original text. By providing a double kind of validation - with both the experiments and the translations - the laboratory thus happened to play a major role in translation. PMID- 27391666 TI - Linnaeus' restless system: translation as textual engineering in eighteenth century botany. AB - In this essay, translations of Linnaeus' Systema naturae into various European languages will be placed into the context of successively expanded editions of Linnaeus' writings. The ambition and intention of most translators was not only to make the Systema naturae accessible for practical botanical use by a wider readership, but also to supplement and correct it, and thus to shape it. By recruiting more users, translations made a significant contribution to keeping the Systema up to date and thus maintaining its practical value for decades. The need to incorporate countless additions and corrections into an existing text, to document their provenance, to identify inconsistencies, and to refer to relevant observations, descriptions, and illustrations in the botanical literature all helped to develop and refine techniques of textual montage. This form of textual engineering, becoming increasingly complex with each translation cycle, shaped the external appearance of new editions of the Systema, and reflected the modular architecture of a botanical system designed for expansion. PMID- 27391667 TI - Outward bound: women translators and scientific travel writing, 1780-1800. AB - As the Enlightenment drew to a close, translation had gradually acquired an increasingly important role in the international circulation and transmission of scientific knowledge. Yet comparatively little attention has been paid to the translators responsible for making such accounts accessible in other languages, some of whom were women. In this article I explore how European women cast themselves as intellectually enquiring, knowledgeable and authoritative figures in their translations. Focusing specifically on the genre of scientific travel writing, I investigate the narrative strategies deployed by women translators to mark their involvement in the process of scientific knowledge-making. These strategies ranged from rhetorical near-invisibility, driven by women's modest marginalization of their own public engagement in science, to the active advertisement of themselves as intellectually curious consumers of scientific knowledge. A detailed study of Elizabeth Helme's translation of the French ornithologist Francois le Vaillant's Voyage dans l'interieur de l'Afrique [Voyage into the Interior of Africa] (1790) allows me to explore how her reworking of the original text for an Anglophone reading public enabled her to engage cautiously - or sometimes more openly - with questions regarding how scientific knowledge was constructed, for whom and with which aims in mind. PMID- 27391668 TI - Before words: reading western astronomical texts in early nineteenth-century Japan. AB - In 1803, the most prominent Japanese astronomer of his time, Takahashi Yoshitoki, received a newly imported Dutch translation of J. J. Lalande's 'Astronomie'. He could not read Dutch, yet he dedicated almost a year to a close examination of this massive work, taking notes and contemplating his own astronomical practices. How did he read a book he could not read? Following the clues Yoshitoki left in his notes, we discover that he found meanings not only in words, but also in what are often taken for granted or considered to be auxiliary tools for data manipulation, such as symbols, units, tables, and diagrams. His rendering of these non-verbal textual elements into a familiar format was crucial for Yoshitoki's reading, and constituted the initial step in the process of integrating Lalande's astronomy into Japanese astronomical practices, and the subsequent translation of the text into Japanese. PMID- 27391669 TI - The publication strategies of Jons Jacob Berzelius (1779-1848): negotiating national and linguistic boundaries in chemistry. AB - This article follows the publication strategies of the Swedish chemist Jons Jacob Berzelius (1779-1848). It focuses on the role of language and translation in Berzelius' efforts to strengthen his own reputation, and that of Swedish science. As an author and editor, Berzelius encouraged the translation of his own works into several languages, while endeavouring to preserve the status of Swedish as a language of scientific publication in the face of French, and increasingly German and English, dominance. Reforming the Transactions of the Royal Swedish Academy of Sciences and launching several new scientific periodicals, Berzelius also attempted to influence the publication practices in other countries. Recent scholarship on the history of scientific publication has drawn attention to the practical difficulties of determining and getting hold of the relevant publications in one's field, the 'malleability' of the journal medium, and the common practice of reprinting and summarising papers published elsewhere. Berzelius' publication strategies highlight translation - time-consuming, unreliable and problematic in terms of authorisation and ownership - as one aspect of the wider problem of communicating across national and linguistic boundaries. Berzelius' struggles with the practicalities of communicating across borders in times of war, the choice of language and its consequences, and national standards of publication, demonstrate the importance of a transnational perspective on the history of scientific publication. PMID- 27391670 TI - The Dostoevsky Machine in Georgetown: scientific translation in the Cold War. AB - Machine Translation (MT) is now ubiquitous in discussions of translation. The roots of this phenomenon - first publicly unveiled in the so-called 'Georgetown IBM Experiment' on 9 January 1954 - displayed not only the technological utopianism still associated with dreams of a universal computer translator, but was deeply enmeshed in the political pressures of the Cold War and a dominating conception of scientific writing as both the goal of machine translation as well as its method. Machine translation was created, in part, as a solution to a perceived crisis sparked by the massive expansion of Soviet science. Scientific prose was also perceived as linguistically simpler, and so served as the model for how to turn a language into a series of algorithms. This paper follows the rise of the Georgetown program - the largest single program in the world - from 1954 to the (as it turns out, temporary) collapse of MT in 1964. PMID- 27391671 TI - Study of Model Systems for Bilirubin and Bilin Chromophores: Determination and Modification of Thermal and Photochemical Properties. AB - Bilin chromophores and bilirubin are involved in relevant biological functions such as light perception in plants and as protective agents against Alzheimer and other diseases. Despite their extensive use, a deep rationalization of the main factors controlling the thermal and photochemical properties has not been performed yet, which in turn hampers further applications of these versatile molecules. In an effort to understand those factors and allow control of the relevant properties, a combined experimental and computational study has been carried out for diverse model systems to understand the interconversion between Z and E isomers. In this study, we have demonstrated the crucial role of steric hindrance and hydrogen-bond interactions in thermal stability and the ability to control them by designing novel compounds. We also determined several photochemical properties and studied the photodynamics of two model systems in more detail, observing a fast relaxation of the excited state shorter than 2 ps in both cases. Finally, the computational study allowed us to rationalize the experimental evidence. PMID- 27391672 TI - Energy Dependence of Measured CT Numbers on Substituted Materials Used for CT Number Calibration of Radiotherapy Treatment Planning Systems. AB - INTRODUCTION: For accurate dose calculations, it is necessary to provide a correct relationship between the CT numbers and electron density in radiotherapy treatment planning systems (TPSs). The purpose of this study was to investigate the energy dependence of measured CT numbers on substituted materials used for CT number calibration of radiotherapy TPSs and the resulting errors in the treatment planning calculation doses. MATERIALS AND METHODS: In this study, we designed a cylindrical water phantom with different materials used as tissue equivalent materials for the simulation of tissues and obtaining the related CT numbers. For evaluating the effect of CT number variations of substituted materials due to energy changing of scanner (kVp) on the dose calculation of TPS, the slices of the scanned phantom at three kVp's were imported into the desired TPSs (MIRS and CorePLAN). Dose calculations were performed on two TPSs. RESULTS: The mean absolute percentage differences between the CT numbers of CT scanner and two treatment planning systems for all the samples were 3.22%+/-2.57% for CorePLAN and 2.88%+/-2.11% for MIRS. It was also found that the maximum absolute percentage difference between all of the calculated doses from each photon beam of linac (6 and 15 MV) at three kVp's was less than 1.2%. DISCUSSION: The present study revealed that, for the materials with effective low atomic number, the mean CT number increased with increasing energy, which was opposite for the materials with an effective high atomic number. We concluded that the tissue substitute materials had a different behavior in the energy ranges from 80 to 130 kVp. So, it is necessary to consider the energy dependence of the substitute materials used for the measurement or calibration of CT number for radiotherapy treatment planning systems. PMID- 27391673 TI - Characterization of an Indole-3-Acetamide Hydrolase from Alcaligenes faecalis subsp. parafaecalis and Its Application in Efficient Preparation of Both Enantiomers of Chiral Building Block 2,3-Dihydro-1,4-Benzodioxin-2-Carboxylic Acid. AB - Both the enantiomers of 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid are valuable chiral synthons for enantiospecific synthesis of therapeutic agents such as (S)-doxazosin mesylate, WB 4101, MKC 242, 2,3-dihydro-2-hydroxymethyl-1,4 benzodioxin, and N-[2,4-oxo-1,3-thiazolidin-3-yl]-2,3-dihydro-1,4-benzodioxin-2 carboxamide. Pharmaceutical applications require these enantiomers in optically pure form. However, currently available methods suffer from one drawback or other, such as low efficiency, uncommon and not so easily accessible chiral resolving agent and less than optimal enantiomeric purity. Our interest in finding a biocatalyst for efficient production of enantiomerically pure 2,3 dihydro-1,4-benzodioxin-2-carboxylic acid lead us to discover an amidase activity from Alcaligenes faecalis subsp. parafaecalis, which was able to kinetically resolve 2,3-dihydro-1,4-benzodioxin-2-carboxyamide with E value of >200. Thus, at about 50% conversion, (R)-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid was produced in >99% e.e. The remaining amide had (S)-configuration and 99% e.e. The amide and acid were easily separated by aqueous (alkaline)-organic two phase extraction method. The same amidase was able to catalyse, albeit at much lower rate the hydrolysis of (S)-amide to (S)-acid without loss of e.e. The amidase activity was identified as indole-3-acetamide hydrolase (IaaH). IaaH is known to catalyse conversion of indole-3-acetamide (IAM) to indole-3-acetic acid (IAA), which is phytohormone of auxin class and is widespread among plants and bacteria that inhabit plant rhizosphere. IaaH exhibited high activity for 2,3-dihydro-1,4 benzodioxin-2-carboxamide, which was about 65% compared to its natural substrate, indole-3-acetamide. The natural substrate for IaaH indole-3-acetamide shared, at least in part a similar bicyclic structure with 2,3-dihydro-1,4-benzodioxin-2 carboxamide, which may account for high activity of enzyme towards this un natural substrate. To the best of our knowledge this is the first application of IaaH in production of industrially important molecules. PMID- 27391674 TI - Correction: Embodied Greenhouse Gas Emissions in Diets. AB - [This corrects the article DOI: 10.1371/journal.pone.0062228.]. PMID- 27391677 TI - Learning Theory Estimates with Observations from General Stationary Stochastic Processes. AB - This letter investigates the supervised learning problem with observations drawn from certain general stationary stochastic processes. Here by general, we mean that many stationary stochastic processes can be included. We show that when the stochastic processes satisfy a generalized Bernstein-type inequality, a unified treatment on analyzing the learning schemes with various mixing processes can be conducted and a sharp oracle inequality for generic regularized empirical risk minimization schemes can be established. The obtained oracle inequality is then applied to derive convergence rates for several learning schemes such as empirical risk minimization (ERM), least squares support vector machines (LS SVMs) using given generic kernels, and SVMs using gaussian kernels for both least squares and quantile regression. It turns out that for independent and identically distributed (i.i.d.) processes, our learning rates for ERM recover the optimal rates. For non-i.i.d. processes, including geometrically [Formula: see text]-mixing Markov processes, geometrically [Formula: see text]-mixing processes with restricted decay, [Formula: see text]-mixing processes, and (time reversed) geometrically [Formula: see text]-mixing processes, our learning rates for SVMs with gaussian kernels match, up to some arbitrarily small extra term in the exponent, the optimal rates. For the remaining cases, our rates are at least close to the optimal rates. As a by-product, the assumed generalized Bernstein type inequality also provides an interpretation of the so-called effective number of observations for various mixing processes. PMID- 27391676 TI - Functional Differentiation of Antiporter-Like Polypeptides in Complex I; a Site Directed Mutagenesis Study of Residues Conserved in MrpA and NuoL but Not in MrpD, NuoM, and NuoN. AB - It has long been known that the three largest subunits in the membrane domain (NuoL, NuoM and NuoN) of complex I are homologous to each other, as well as to two subunits (MrpA and MrpD) from a Na+/H+ antiporter, Mrp. MrpA and NuoL are more similar to each other and the same is true for MrpD and NuoN. This suggests a functional differentiation which was proven experimentally in a deletion strain model system, where NuoL could restore the loss of MrpA, but not that of MrpD and vice versa. The simplest explanation for these observations was that the MrpA and MrpD proteins are not antiporters, but rather single subunit ion channels that together form an antiporter. In this work our focus was on a set of amino acid residues in helix VIII, which are only conserved in NuoL and MrpA (but not in any of the other antiporter-like subunits.) and to compare their effect on the function of these two proteins. By combining complementation studies in B. subtilis and 23Na-NMR, response of mutants to high sodium levels were tested. All of the mutants were able to cope with high salt levels; however, all but one mutation (M258I/M225I) showed differences in the efficiency of cell growth and sodium efflux. Our findings showed that, although very similar in sequence, NuoL and MrpA seem to differ on the functional level. Nonetheless the studied mutations gave rise to interesting phenotypes which are of interest in complex I research. PMID- 27391675 TI - The efficacy of behavioural activation treatment for co-occurring depression and substance use disorder (the activate study): a randomized controlled trial. AB - BACKGROUND: Epidemiological studies suggest that compared with the general population, mood disorders are up to 4.7 times more prevalent in substance dependent samples. Comorbid substance use disorder (SUD) and depression has been associated with a more severe and protracted illness course and poorer treatment outcomes. Despite this, the development and assessment of behavioural interventions for treating depression among individuals with SUDs have received little empirical attention. Behavioural Activation Treatment for Depression (BATD R) is an empirically supported treatment for depression that has shown some efficacy among substance users. This paper describes the study protocol of a parallel, single blind, randomised controlled trial to determine the efficacy and feasibility of a modified version of the BATD-R (Activate) in reducing symptoms of depression and substance dependence among individuals in residential rehabilitation (RR) and opioid substitution therapy (OST). METHODS/DESIGN: A sample of approximately 200 individuals with depressive symptomatology in treatment for SUD will be recruited from RR and OST services in New South Wales, Australia. Dynamic random allocation following minimisation methodology will be used to assign participants to one of two groups. The control group will receive treatment as usual (TAU), which will be the model of care provided in accordance with standard practice at participating RR and OST services. The intervention group will receive Activate, comprising 10 individual 60-min therapy sessions with a psychologist employed on the research team, in addition to TAU. Data collection will occur at baseline (pre-intervention), and 3-months and 12-months post baseline. DISCUSSION: The association between depression and substance dependence has been well documented, yet practical and effective treatments are scarce. The findings of the present study will contribute significantly to understanding the types of programs that are effective in treating this comorbidity. TRIAL REGISTRATION: This trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12613000876796 . Registered on 7 August, 2013. PMID- 27391679 TI - Dimensionality-Dependent Generalization Bounds for k-Dimensional Coding Schemes. AB - The k-dimensional coding schemes refer to a collection of methods that attempt to represent data using a set of representative k-dimensional vectors and include nonnegative matrix factorization, dictionary learning, sparse coding, k-means clustering, and vector quantization as special cases. Previous generalization bounds for the reconstruction error of the k-dimensional coding schemes are mainly dimensionality-independent. A major advantage of these bounds is that they can be used to analyze the generalization error when data are mapped into an infinite- or high-dimensional feature space. However, many applications use finite-dimensional data features. Can we obtain dimensionality-dependent generalization bounds for k-dimensional coding schemes that are tighter than dimensionality-independent bounds when data are in a finite-dimensional feature space? Yes. In this letter, we address this problem and derive a dimensionality dependent generalization bound for k-dimensional coding schemes by bounding the covering number of the loss function class induced by the reconstruction error. The bound is of order [Formula: see text], where m is the dimension of features, k is the number of the columns in the linear implementation of coding schemes, and n is the size of sample, [Formula: see text] when n is finite and [Formula: see text] when n is infinite. We show that our bound can be tighter than previous results because it avoids inducing the worst-case upper bound on k of the loss function. The proposed generalization bound is also applied to some specific coding schemes to demonstrate that the dimensionality-dependent bound is an indispensable complement to the dimensionality-independent generalization bounds. PMID- 27391680 TI - Linking Neuromodulated Spike-Timing Dependent Plasticity with the Free-Energy Principle. AB - The free-energy principle is a candidate unified theory for learning and memory in the brain that predicts that neurons, synapses, and neuromodulators work in a manner that minimizes free energy. However, electrophysiological data elucidating the neural and synaptic bases for this theory are lacking. Here, we propose a novel theory bridging the information-theoretical principle with the biological phenomenon of spike-timing dependent plasticity (STDP) regulated by neuromodulators, which we term mSTDP. We propose that by integrating an mSTDP equation, we can obtain a form of Friston's free energy (an information theoretical function). Then we analytically and numerically show that dopamine (DA) and noradrenaline (NA) influence the accuracy of a principal component analysis (PCA) performed using the mSTDP algorithm. From the perspective of free energy minimization, these neuromodulatory changes alter the relative weighting or precision of accuracy and prior terms, which induces a switch from pattern completion to separation. These results are consistent with electrophysiological findings and validate the free-energy principle and mSTDP. Moreover, our scheme can potentially be applied in computational psychiatry to build models of the faulty neural networks that underlie the positive symptoms of schizophrenia, which involve abnormal DA levels, as well as models of the NA contribution to memory triage and posttraumatic stress disorder. PMID- 27391678 TI - Dynamic Multiscale Modes of Resting State Brain Activity Detected by Entropy Field Decomposition. AB - The ability of functional magnetic resonance imaging (FMRI) to noninvasively measure fluctuations in brain activity in the absence of an applied stimulus offers the possibility of discerning functional networks in the resting state of the brain. However, the reconstruction of brain networks from these signal fluctuations poses a significant challenge because they are generally nonlinear and nongaussian and can overlap in both their spatial and temporal extent. Moreover, because there is no explicit input stimulus, there is no signal model with which to compare the brain responses. A variety of techniques have been devised to address this problem, but the predominant approaches are based on the presupposition of statistical properties of complex brain signal parameters, which are unprovable but facilitate the analysis. In this article, we address this problem with a new method, entropy field decomposition, for estimating structure within spatiotemporal data. This method is based on a general information field-theoretic formulation of Bayesian probability theory incorporating prior coupling information that allows the enumeration of the most probable parameter configurations without the need for unjustified statistical assumptions. This approach facilitates the construction of brain activation modes directly from the spatial-temporal correlation structure of the data. These modes and their associated spatial-temporal correlation structure can then be used to generate space-time activity probability trajectories, called functional connectivity pathways, which provide a characterization of functional brain networks. PMID- 27391681 TI - Active Inference and Learning in the Cerebellum. AB - This letter offers a computational account of Pavlovian conditioning in the cerebellum based on active inference and predictive coding. Using eyeblink conditioning as a canonical paradigm, we formulate a minimal generative model that can account for spontaneous blinking, startle responses, and (delay or trace) conditioning. We then establish the face validity of the model using simulated responses to unconditioned and conditioned stimuli to reproduce the sorts of behavior that are observed empirically. The scheme's anatomical validity is then addressed by associating variables in the predictive coding scheme with nuclei and neuronal populations to match the (extrinsic and intrinsic) connectivity of the cerebellar (eyeblink conditioning) system. Finally, we try to establish predictive validity by reproducing selective failures of delay conditioning, trace conditioning, and extinction using (simulated and reversible) focal lesions. Although rather metaphorical, the ensuing scheme can account for a remarkable range of anatomical and neurophysiological aspects of cerebellar circuitry-and the specificity of lesion-deficit mappings that have been established experimentally. From a computational perspective, this work shows how conditioning or learning can be formulated in terms of minimizing variational free energy (or maximizing Bayesian model evidence) using exactly the same principles that underlie predictive coding in perception. PMID- 27391682 TI - Learning Minimal Latent Directed Information Polytrees. AB - We propose an approach for learning latent directed polytrees as long as there exists an appropriately defined discrepancy measure between the observed nodes. Specifically, we use our approach for learning directed information polytrees where samples are available from only a subset of processes. Directed information trees are a new type of probabilistic graphical models that represent the causal dynamics among a set of random processes in a stochastic system. We prove that the approach is consistent for learning minimal latent directed trees. We analyze the sample complexity of the learning task when the empirical estimator of mutual information is used as the discrepancy measure. PMID- 27391683 TI - A Mathematical Framework for Statistical Decision Confidence. AB - Decision confidence is a forecast about the probability that a decision will be correct. From a statistical perspective, decision confidence can be defined as the Bayesian posterior probability that the chosen option is correct based on the evidence contributing to it. Here, we used this formal definition as a starting point to develop a normative statistical framework for decision confidence. Our goal was to make general predictions that do not depend on the structure of the noise or a specific algorithm for estimating confidence. We analytically proved several interrelations between statistical decision confidence and observable decision measures, such as evidence discriminability, choice, and accuracy. These interrelationships specify necessary signatures of decision confidence in terms of externally quantifiable variables that can be empirically tested. Our results lay the foundations for a mathematically rigorous treatment of decision confidence that can lead to a common framework for understanding confidence across different research domains, from human and animal behavior to neural representations. PMID- 27391684 TI - The Geometry of Plasticity-Induced Sensitization in Isoinhibitory Rate Motifs. AB - A well-known phenomenon in sensory perception is desensitization, wherein behavioral responses to persistent stimuli become attenuated over time. In this letter, our focus is on studying mechanisms through which desensitization may be mediated at the network level and, specifically, how sensitivity changes arise as a function of long-term plasticity. Our principal object of study is a generic isoinhibitory motif: a small excitatory-inhibitory network with recurrent inhibition. Such a motif is of interest due to its overrepresentation in laminar sensory network architectures. Here, we introduce a sensitivity analysis derived from control theory in which we characterize the fixed-energy reachable set of the motif. This set describes the regions of the phase-space that are more easily (in terms of stimulus energy) accessed, thus providing a holistic assessment of sensitivity. We specifically focus on how the geometry of this set changes due to repetitive application of a persistent stimulus. We find that for certain motif dynamics, this geometry contracts along the stimulus orientation while expanding in orthogonal directions. In other words, the motif not only desensitizes to the persistent input, but heightens its responsiveness (sensitizes) to those that are orthogonal. We develop a perturbation analysis that links this sensitization to both plasticity-induced changes in synaptic weights and the intrinsic dynamics of the network, highlighting that the effect is not purely due to weight-dependent disinhibition. Instead, this effect depends on the relative neuronal time constants and the consequent stimulus-induced drift that arises in the motif phase-space. For tightly distributed (but random) parameter ranges, sensitization is quite generic and manifests in larger recurrent E-I networks within which the motif is embedded. PMID- 27391685 TI - Complex Neural Network Models for Time-Varying Drazin Inverse. AB - Two complex Zhang neural network (ZNN) models for computing the Drazin inverse of arbitrary time-varying complex square matrix are presented. The design of these neural networks is based on corresponding matrix-valued error functions arising from the limit representations of the Drazin inverse. Two types of activation functions, appropriate for handling complex matrices, are exploited to develop each of these networks. Theoretical results of convergence analysis are presented to show the desirable properties of the proposed complex-valued ZNN models. Numerical results further demonstrate the effectiveness of the proposed models. PMID- 27391686 TI - The Enhanced Rise and Delayed Fall of Memory in a Model of Synaptic Integration: Extension to Discrete State Synapses. AB - Integrate-and-express models of synaptic plasticity propose that synapses may act as low-pass filters, integrating synaptic plasticity induction signals in order to discern trends before expressing synaptic plasticity. We have previously shown that synaptic filtering strongly controls destabilizing fluctuations in developmental models. When applied to palimpsest memory systems that learn new memories by forgetting old ones, we have also shown that with binary-strength synapses, integrative synapses lead to an initial memory signal rise before its fall back to equilibrium. Such an initial rise is in dramatic contrast to nonintegrative synapses, in which the memory signal falls monotonically. We now extend our earlier analysis of palimpsest memories with synaptic filters to consider the more general case of discrete state, multilevel synapses. We derive exact results for the memory signal dynamics and then consider various simplifying approximations. We show that multilevel synapses enhance the initial rise in the memory signal and then delay its subsequent fall by inducing a plateau-like region in the memory signal. Such dynamics significantly increase memory lifetimes, defined by a signal-to-noise ratio (SNR). We derive expressions for optimal choices of synaptic parameters (filter size, number of strength states, number of synapses) that maximize SNR memory lifetimes. However, we find that with memory lifetimes defined via mean-first-passage times, such optimality conditions do not exist, suggesting that optimality may be an artifact of SNRs. PMID- 27391687 TI - Dynamic Signal Tracking in a Simple V1 Spiking Model. AB - This work is part of an effort to understand the neural basis for our visual system's ability, or failure, to accurately track moving visual signals. We consider here a ring model of spiking neurons, intended as a simplified computational model of a single hypercolumn of the primary visual cortex of primates. Signals that consist of edges with time-varying orientations localized in space are considered. Our model is calibrated to produce spontaneous and driven firing rates roughly consistent with experiments, and our two main findings, for which we offer dynamical explanation on the level of neuronal interactions, are the following. First, we have documented consistent transient overshoots in signal perception following signal switches due to emergent interactions of the E- and I-populations. Second, for continuously moving signals, we have found that accuracy is considerably lower at reversals of orientation than when continuing in the same direction (as when the signal is a rotating bar). To measure performance, we use two metrics, called fidelity and reliability, to compare signals reconstructed by the system to the ones presented and assess trial-to-trial variability. We propose that the same population mechanisms responsible for orientation selectivity also impose constraints on dynamic signal tracking that manifest in perception failures consistent with psychophysical observations. PMID- 27391688 TI - Pattern Completion in Symmetric Threshold-Linear Networks. AB - Threshold-linear networks are a common class of firing rate models that describe recurrent interactions among neurons. Unlike their linear counterparts, these networks generically possess multiple stable fixed points (steady states), making them viable candidates for memory encoding and retrieval. In this work, we characterize stable fixed points of general threshold-linear networks with constant external drive and discover constraints on the coexistence of fixed points involving different subsets of active neurons. In the case of symmetric networks, we prove the following antichain property: if a set of neurons [Formula: see text] is the support of a stable fixed point, then no proper subset or superset of [Formula: see text] can support a stable fixed point. Symmetric threshold-linear networks thus appear to be well suited for pattern completion, since the dynamics are guaranteed not to get stuck in a subset or superset of a stored pattern. We also show that for any graph G, we can construct a network whose stable fixed points correspond precisely to the maximal cliques of G. As an application, we design network decoders for place field codes and demonstrate their efficacy for error correction and pattern completion. The proofs of our main results build on the theory of permitted sets in threshold-linear networks, including recently developed connections to classical distance geometry. PMID- 27391689 TI - A Mathematical Model that Simulates Control Options for African Swine Fever Virus (ASFV). AB - A stochastic model designed to simulate transmission dynamics of African swine fever virus (ASFV) in a free-ranging pig population under various intervention scenarios is presented. The model was used to assess the relative impact of the timing of the implementation of different control strategies on disease-related mortality. The implementation of biosecurity measures was simulated through incorporation of a decay function on the transmission rate. The model predicts that biosecurity measures implemented within 14 days of the onset of an epidemic can avert up to 74% of pig deaths due to ASF while hypothetical vaccines that confer 70% immunity when deployed prior to day 14 of the epidemic could avert 65% of pig deaths. When the two control measures are combined, the model predicts that 91% of the pigs that would have otherwise succumbed to the disease if no intervention was implemented would be saved. However, if the combined interventions are delayed (defined as implementation from > 60 days) only 30% of ASF-related deaths would be averted. In the absence of vaccines against ASF, we recommend early implementation of enhanced biosecurity measures. Active surveillance and use of pen-side diagnostic assays, preferably linked to rapid dissemination of this data to veterinary authorities through mobile phone technology platforms are essential for rapid detection and confirmation of ASF outbreaks. This prediction, although it may seem intuitive, rationally confirms the importance of early intervention in managing ASF epidemics. The modelling approach is particularly valuable in that it determines an optimal timing for implementation of interventions in controlling ASF outbreaks. PMID- 27391690 TI - RuBisCO in Non-Photosynthetic Alga Euglena longa: Divergent Features, Transcriptomic Analysis and Regulation of Complex Formation. AB - Euglena longa, a close relative of the photosynthetic model alga Euglena gracilis, possesses an enigmatic non-photosynthetic plastid. Its genome has retained a gene for the large subunit of the enzyme RuBisCO (rbcL). Here we provide new data illuminating the putative role of RuBisCO in E. longa. We demonstrated that the E. longa RBCL protein sequence is extremely divergent compared to its homologs from the photosynthetic relatives, suggesting a possible functional shift upon the loss of photosynthesis. Similarly to E. gracilis, E. longa harbors a nuclear gene encoding the small subunit of RuBisCO (RBCS) as a precursor polyprotein comprising multiple RBCS repeats, but one of them is highly divergent. Both RBCL and the RBCS proteins are synthesized in E. longa, but their abundance is very low compared to E. gracilis. No RBCS monomers could be detected in E. longa, suggesting that processing of the precursor polyprotein is inefficient in this species. The abundance of RBCS is regulated post transcriptionally. Indeed, blocking the cytoplasmic translation by cycloheximide has no immediate effect on the RBCS stability in photosynthetically grown E. gracilis, but in E. longa, the protein is rapidly degraded. Altogether, our results revealed signatures of evolutionary degradation (becoming defunct) of RuBisCO in E. longa and suggest that its biological role in this species may be rather unorthodox, if any. PMID- 27391691 TI - A case report of ophthalmic artery emboli secondary to Calcium Hydroxylapatite filler injection for nose augmentation- long-term outcome. AB - BACKGROUND: Filler injection for face augmentation is a common cosmetic procedure in the last decades, in our case report we describe long-term outcomes of a devastating complication of ophthalmic artery emboli following Calcium Hydroxylapatite filler injection to the nose bridge. CASE PRESENTATION: A healthy 24-year-old women received a Calcium Hydroxylapatite filler injection to her nose bridge for the correction of nose asymmetry 8 years post rhinoplasty. She developed sudden right eye ocular pain and visual disturbances. Visual acuity was 20/20 in both eyes and visual field in the right eye showed inferior arch with fixation sparing and supero-temporal central scotoma. Examination revealed marked periorbital edema and hematoma, ptosis, ocular movements limitation, an infero temporal branch retinal artery occlusion and multiple choroidal emboli. Eighteen months post initial presentation ptosis and eye movements returned normal and choroidal emboli absorbed almost completely. However, visual acuity declined to 20/60, visual field showed severe progressive deterioration with a central and supero-nasal field remnant and the optic disc became pallor. CONCLUSION: Cosmetic injection of calcium hydroxylapatite to the nose bridge can result in arterial emboli to the ophthalmic system with optic nerve, retinal and choroidal involvement causing long term severe visual acuity and visual field impairment. PMID- 27391692 TI - The Influence of Vesicle Shape and Medium Conductivity on Possible Electrofusion under a Pulsed Electric Field. AB - The effects of electric field on lipid membrane and cells have been extensively studied in the last decades. The phenomena of electroporation and electrofusion are of particular interest due to their wide use in cell biology and biotechnology. However, numerical studies on the electrofusion of cells (or vesicles) with different deformed shapes are still rare. Vesicle, being of cell size, can be treated as a simple model of cell to investigate the behaviors of cell in electric field. Based on the finite element method, we investigate the effect of vesicle shape on electrofusion of contact vesicles in various medium conditions. The transmembrane voltage (TMV) and pore density induced by a pulsed field are examined to analyze the possibility of vesicle fusion. In two different medium conditions, the prolate shape is observed to have selective electroporation at the contact area of vesicles when the exterior conductivity is smaller than the interior one; selective electroporation is more inclined to be found at the poles of the oblate vesicles when the exterior conductivity is larger than the interior one. Furthermore, we find that when the exterior conductivity is lower than the internal conductivity, the pulse can induce a selective electroporation at the contact area between two vesicles regardless of the vesicle shape. Both of these two findings have important practical applications in guiding electrofusion experiments. PMID- 27391693 TI - Real-time digital pathogen surveillance - the time is now. AB - It is time to shake up public health surveillance. New technologies for sequencing, aided by friction-free approaches to data sharing, could have an impact on public health efforts. PMID- 27391694 TI - Chemical Vapor Deposition Synthesis of Ultrathin Hexagonal ReSe2 Flakes for Anisotropic Raman Property and Optoelectronic Application. AB - Hexagonal crystalline ultrathin ReSe2 flakes are synthesized for the first time by a chemical vapor deposition (CVD) method. The as-synthesized ReSe2 flake is revealed as a novel structure, which has mirror-symmetric single-crystal domains inside, by polarization incident Raman and HRTEM. The successful development of the CVD method will facilitate research on the novel anisotropic electronic/optoelectronic properties of ReSe2 in the future. PMID- 27391695 TI - Co-designing inflammatory bowel disease (Ibd) services in Scotland: findings from a nationwide survey. AB - BACKGROUND: The Scottish Government's ambition is to ensure that health services are co-designed with the communities they serve. Crohn's and Colitis UK and the Scottish Government acknowledged the need to review and update the current IBD care model. An online survey was conducted asking IBD patients about their experiences of the NHS care they receive. This survey was the first step of co designing and developing a national strategy for IBD service improvement in Scotland. AIM: To explore IBD patients' experiences of current services and make recommendations for future service development. METHODS: This study was part of a wider cross-sectional on-line survey. Participants were patients with IBD across Scotland. 777 people with IBD took part in the survey. Thematic analysis of all data was conducted independently by two researchers. RESULTS: Three key themes emerged: Quality of life: Participants highlighted the impact the disease has on quality of life and the desperate need for IBD services to address this more holistically. IBD clinicians and access: Participants recognised the need for more IBD nurses and gastroenterologists along with better access to them. Those with a named IBD nurse reported to be more satisfied with their care. An explicit IBD care pathway: Patients with IBD identified the need of making the IBD care pathway more explicit to service users. CONCLUSIONS: Participants expressed the need for a more holistic approach to their IBD care. This includes integrating psychological, counselling and dietetic services into IBD care with better access to IBD clinicians and a more explicit IBD care pathway. PMID- 27391696 TI - Cognitive function and short-term exposure to residential air temperature: A repeated measures study based on spatiotemporal estimates of temperature. AB - Few studies have examined the association between ambient temperature and cognitive function, or used exposure to temperature at a given address instead of a single stationary monitor. The existing literature on the temperature-cognition relationship has mostly consisted of experimental studies that involve a small sample size and a few specific temperature values. In the current study, we examined the association between residential air temperature and Mini-Mental State Examination (MMSE) scores, a quantitative measurement of cognitive function, in a longitudinal cohort of elderly men. Residential air temperature was estimated by a novel spatiotemporal approach that incorporates satellite remote sensing, land use regression, meteorological variables and spatial smoothing in the Northeastern USA. We then applied logistic regression generalized estimating equations to examine the relationship between residential temperature (range: -5.8-25.7 degrees C), and the risk of low MMSE scores (MMSE scores <=25) among 594 elderly men (1085 visits in total) from the Veterans Affairs Normative Aging Study, 2000-2008. Sensitivity analysis on visits wherein subjects lived within 30km of the clinic center in Massachusetts or aged >=70 years was also evaluated. A statistically significant, U-shaped association between residential air temperature and low MMSE score (p-value=0.036) was observed. Sensitivity analysis suggested that the estimated effect remains among individuals aged >=70 years. In conclusion, the data suggest that risk of low MMSE scores is highest when temperature is either high or low, and lowest when ambient temperature is approximately within 10-15 degrees C in a cohort of elderly men. Further research is needed to confirm our findings and assess generalizability to other populations. PMID- 27391699 TI - Two Distinct Episodes Of Whooping Cough Caused By Consecutive Bordetella Pertussis And Bordetella Parapertussis Infections In A Fully Immunized Healthy Boy. AB - We describe a 5-year-old, fully immunized boy with polymerase chain reaction proven consecutive Bordetella pertussis and Bordetella parapertussis infections causing typical whooping cough at the age of 2 and 5 years, respectively. Neither pertussis immunization nor disease provides reliable immunity against further episodes of whooping cough. PMID- 27391697 TI - Effectiveness of a Closed-System Transfer Device in Reducing Surface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled, Parallel Study. AB - BACKGROUND: The objective of this randomized, prospective and controlled study was to investigate the ability of a closed-system transfer device (CSTD; BD Phaseal) to reduce the occupational exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding devices. METHODS AND FINDINGS: The 6 month study started with the opening of a new compounding unit. Two isolators were set up with 2 workstations each, one to compound with standard devices (needles and spikes) and the other using the Phaseal system. Drugs were alternatively compounded in each isolator. Sampling involved wiping three surfaces (gloves, window, worktop), before and after a cleaning process. Exposure to ten antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-FU, methotrexate, gemcitabine, cytarabine, irinotecan, doxorubicine and ganciclovir) was assessed on wipes by LC-MS/MS analysis. Contamination rates were compared using a Chi2 test and drug amounts by a Mann-Whitney test. Significance was defined for p<0.05. Overall contamination was lower in the "Phaseal" isolator than in the "Standard" isolator (12.24% vs. 26.39%; p < 0.0001) although it differed according to drug. Indeed, the contamination rates of gemcitabine were 49.3 and 43.4% (NS) for the Standard and Phaseal isolators, respectively, whereas for ganciclovir, they were 54.2 and 2.8% (p<0.0001). Gemcitabine amounts were 220.6 and 283.6 ng for the Standard and Phaseal isolators (NS), and ganciclovir amounts were 179.9 and 2.4 ng (p<0.0001). CONCLUSION: This study confirms that using a CSTD may significantly decrease the chemical contamination of barrier isolators compared to standard devices for some drugs, although it does not eliminate contamination totally. PMID- 27391698 TI - Inhibitory action on the production of advanced glycation end products (AGEs) and suppression of free radicals in vitro by a Sri Lankan polyherbal formulation Nawarathne Kalka. AB - BACKGROUND: Advanced glycation end products (AGEs) and free radicals are inflammatory mediators and are implicated in many diseases such as diabetes, cancer, rheumatoid arthritis etc. Multi targeted poly herbal drug systems like Nawarathne Kalka (NK) are able to quench the overall effect of these mediators as they contain good combinations of phytochemicals that have least side effects in contrast to modern medicinal drugs. The objectives of this study were to evaluate phytochemical composition, free radical scavenging activity, cytotoxicity and the inhibitory action on the formation of AGEs by aqueous extract of NK. METHODS: Total phenolic content (TPC) and total flavonoid content (TFC) were determined using Folin ciocalteu method and aluminium chloride assay respectively. Free radical scavenging activity was assessed by DPPH radical scavenging assay (DRSA), phosphomolybdenum reduction antioxidant assay (PRAA) and nitric oxide (NO) scavenging assay. Brine Shrimp Lethality (BSL) bioassay was performed as preliminary screening for cytotoxic activity. Inhibitory action on AGE formation was evaluated using fructose mediated glycation of bovine serum albumin using fluorescence spectroscopic method. RESULTS: The TPC and TFC were 75.1 +/- 3.0 mg/g gallic acid equivalents and 68.7 +/- 7.8 mg/g epigallocatechin gallate equivalents. The DRSA yielded EC50 of 19.15 +/- 2.24 MUg mL(-1) for NK. DRSA of NK extract was greater than butylated hydroxy toluene (EC50 = 96.50 +/- 4.51 MUg mL(-1)) but lesser than L-ascorbic acid (EC50 = 5.60 +/- 0.51 MUg mL(-1)). The total antioxidant capacity of NK as evidenced by PRAA was 106.4 +/- 8.2 mg/g L ascorbic acid equivalents. NK showed EC50 value of 99.3 +/- 8.4 MUg mL(-1) in the NO scavenging assay compared to the standard ascorbic acid (EC50 = 7.3 +/- 0.3 MUg mL(-1)). The extract indicated moderate cytotoxic activity in the BSL bioassay. The extract showed effective inhibitory action on the formation of AGEs with EC50 values of 116 +/- 19 MUg mL(-1), 125 +/- 35 MUg mL(-1) and 84 +/- 28 MUg mL(-1) in data obtained over three consecutive weeks respectively. Comparatively the reference standard, aminoguanidine at a concentration of 500 MUg mL(-1) demonstrated 65 % inhibition on the formation of AGE after one week of sample incubation. CONCLUSIONS: The results proved the potential of NK as a free radical scavenger, moderate cytotoxic agent and an inhibitor on the formation of advanced glycation end-products. PMID- 27391700 TI - Association between C3435T polymorphism of MDR1 gene and the incidence of drug resistant epilepsy in the population of Polish children. AB - PURPOSE: Epilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children. METHODS: C3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the chi(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model. RESULTS: An association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases. CONCLUSION: Following the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014. PMID- 27391702 TI - Functional Modification of Fibrous PCL Scaffolds with Fusion Protein VEGF-HGFI Enhanced Cellularization and Vascularization. AB - The lack of efficient vascularization within frequently used poly(epsilon caprolactone) (PCL) scaffolds has hindered their application in tissue engineering. Hydrophobin HGFI, an amphiphilic protein, can form a self-assembly layer on the surface of PCL scaffolds and convert their wettability. In this study, a fusion protein consisting of HGFI and vascular endothelial growth factor (VEGF) is prepared by Pichia pastoris expression system. Sodium dodecyl sulface polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting confirm that the VEGF-HGFI is successfully isolated and purified. Transmission electron microscope and water contact angle measurement demonstrate that VEGF-HGFI can form a self-assembly layer with about 25 nm in thickness on electrospun PCL fibers and increase their hydrophilicity. VEGF-HGFI modification can effectively enhance the adhesion, migration, and proliferation of human umbilical vein endothelial cells. Near-infrared fluorescence imaging shows that the VEGF-HGFI modification on PCL scaffolds can exist at least 21 d in vitro and at least 14 d in vivo. Bioluminescence imaging shows that VEGF-HGFI can effectively activate vascular endothelial growth factor receptor 2 receptors. Subcutaneous implantation in mice and rats reveal that cellularization and vascularization are significantly improved in VEGF-HGFI modified PCL scaffolds. These results suggest that VEGF-HGFI is a useful molecule for functional modification of scaffolds to enhance cellularization and vascularization in tissue engineering. PMID- 27391703 TI - Thermoplastics Reinforced with Self-Welded Short Carbon Fibers: Nanoparticle Promoted Structural Evolution. AB - The large volume of currently available fiber-reinforced polymer composites critically limits the intrinsic versatility of fibers such as high mechanical strength, heat resistance, and excellent thermal/electrical conductivity. We proposed a facile and widely applicable strategy to promote self-organization of randomly dispersed short carbon fibers (CFs) into a three-dimensionally continuous scaffold. The morphological evolution and structural reinforcement of the self-welded CF-polyamide 6 (PA6) scaffold in polystyrene (PS) matrix were investigated, with carbon black (CB) or titanium dioxide (TiO2) nanoparticles (NPs) selectively localized in the PA6 domains. Surprisingly, all of the PA6 droplets once dispersed in the PS matrix can migrate and evenly encapsulate onto the CF surface when 5.8 wt % CB is incorporated, whereas in the TiO2-filled system, the PA6 droplets preferentially segregate at the junction point of CFs to fasten the self-welded CF structure. In addition, a remarkable increase in the interfacial adhesive work between PA6 and CF was observed only when TiO2 is added, and a loading of even less than 0.8 wt % can effectively abruptly strengthen the self-welded CF scaffold. We clarified that the structural evolution is promoted by the nature of self-agglomeration of NPs. CB is highly capable of self-networking in the PA6 domain, resulting in high encapsulation of PA6, although the capillary force for preferential segregation of PA6 at the junction point of CFs is reduced. By contrast, the TiO2 particles tend to form compact aggregates. Such an agglomeration pattern, together with enhanced interfacial affinity, must contribute to a strong capillary force for the preferential segregation of PA6. PMID- 27391701 TI - Intrinsic Disorder in Transmembrane Proteins: Roles in Signaling and Topology Prediction. AB - Intrinsically disordered regions (IDRs) are peculiar stretches of amino acids that lack stable conformations in solution. Intrinsic Disorder containing Proteins (IDP) are defined by the presence of at least one large IDR and have been linked to multiple cellular processes including cell signaling, DNA binding and cancer. Here we used computational analyses and publicly available databases to deepen insight into the prevalence and function of IDRs specifically in transmembrane proteins, which are somewhat neglected in most studies. We found that 50% of transmembrane proteins have at least one IDR of 30 amino acids or more. Interestingly, these domains preferentially localize to the cytoplasmic side especially of multi-pass transmembrane proteins, suggesting that disorder prediction could increase the confidence of topology prediction algorithms. This was supported by the successful prediction of the topology of the uncharacterized multi-pass transmembrane protein TMEM117, as confirmed experimentally. Pathway analysis indicated that IDPs are enriched in cell projection and axons and appear to play an important role in cell adhesion, signaling and ion binding. In addition, we found that IDP are enriched in phosphorylation sites, a crucial post translational modification in signal transduction, when compared to fully ordered proteins and to be implicated in more protein-protein interaction events. Accordingly, IDPs were highly enriched in short protein binding regions called Molecular Recognition Features (MoRFs). Altogether our analyses strongly support the notion that the transmembrane IDPs act as hubs in cellular signal events. PMID- 27391704 TI - Phase Structure of Driven Quantum Systems. AB - Clean and interacting periodically driven systems are believed to exhibit a single, trivial "infinite-temperature" Floquet-ergodic phase. In contrast, here we show that their disordered Floquet many-body localized counterparts can exhibit distinct ordered phases delineated by sharp transitions. Some of these are analogs of equilibrium states with broken symmetries and topological order, while others-genuinely new to the Floquet problem-are characterized by order and nontrivial periodic dynamics. We illustrate these ideas in driven spin chains with Ising symmetry. PMID- 27391705 TI - Cooperative Shielding in Many-Body Systems with Long-Range Interaction. AB - In recent experiments with ion traps, long-range interactions were associated with the exceptionally fast propagation of perturbation, while in some theoretical works they have also been related with the suppression of propagation. Here, we show that such apparently contradictory behavior is caused by a general property of long-range interacting systems, which we name cooperative shielding. It refers to shielded subspaces that emerge as the system size increases and inside of which the evolution is unaffected by long-range interactions for a long time. As a result, the dynamics strongly depends on the initial state: if it belongs to a shielded subspace, the spreading of perturbation satisfies the Lieb-Robinson bound and may even be suppressed, while for initial states with components in various subspaces, the propagation may be quasi-instantaneous. We establish an analogy between the shielding effect and the onset of quantum Zeno subspaces. The derived effective Zeno Hamiltonian successfully describes the short-ranged dynamics inside the subspaces up to a time scale that increases with system size. Cooperative shielding can be tested in current experiments with trapped ions. PMID- 27391706 TI - Persistent Superfluid Flow Arising from the He-McKellar-Wilkens Effect in Molecular Dipolar Condensates. AB - We show that the He-McKellar-Wilkens effect can induce a persistent flow in a Bose-Einstein condensate of polar molecules confined in a toroidal trap, with the dipolar interaction mediated via an electric dipole moment. For Bose-Einstein condensates of atoms with a magnetic dipole moment, we show that although it is theoretically possible to induce persistent flow via the Aharonov-Casher effect, the strength of the electric field required is prohibitive. We also outline an experimental geometry tailored specifically for observing the He-McKellar-Wilkens effect in toroidally trapped condensates. PMID- 27391707 TI - Classical Physics and the Bounds of Quantum Correlations. AB - A unifying principle explaining the numerical bounds of quantum correlations remains elusive, despite the efforts devoted to identifying it. Here, we show that these bounds are indeed not exclusive to quantum theory: for any abstract correlation scenario with compatible measurements, models based on classical waves produce probability distributions indistinguishable from those of quantum theory and, therefore, share the same bounds. We demonstrate this finding by implementing classical microwaves that propagate along meter-size transmission line circuits and reproduce the probabilities of three emblematic quantum experiments. Our results show that the "quantum" bounds would also occur in a classical universe without quanta. The implications of this observation are discussed. PMID- 27391708 TI - Improved Classical Simulation of Quantum Circuits Dominated by Clifford Gates. AB - We present a new algorithm for classical simulation of quantum circuits over the Clifford+T gate set. The runtime of the algorithm is polynomial in the number of qubits and the number of Clifford gates in the circuit but exponential in the number of T gates. The exponential scaling is sufficiently mild that the algorithm can be used in practice to simulate medium-sized quantum circuits dominated by Clifford gates. The first demonstrations of fault-tolerant quantum circuits based on 2D topological codes are likely to be dominated by Clifford gates due to a high implementation cost associated with logical T gates. Thus our algorithm may serve as a verification tool for near-term quantum computers which cannot in practice be simulated by other means. To demonstrate the power of the new method, we performed a classical simulation of a hidden shift quantum algorithm with 40 qubits, a few hundred Clifford gates, and nearly 50 T gates. PMID- 27391709 TI - Majorana Positivity and the Fermion Sign Problem of Quantum Monte Carlo Simulations. AB - The sign problem is a major obstacle in quantum Monte Carlo simulations for many body fermion systems. We examine this problem with a new perspective based on the Majorana reflection positivity and Majorana Kramers positivity. Two sufficient conditions are proven for the absence of the fermion sign problem. Our proof provides a unified description for all the interacting lattice fermion models previously known to be free of the sign problem based on the auxiliary field quantum Monte Carlo method. It also allows us to identify a number of new sign problem-free interacting fermion models including, but not limited to, lattice fermion models with repulsive interactions but without particle-hole symmetry, and interacting topological insulators with spin-flip terms. PMID- 27391710 TI - Departures from the Friedmann-Lemaitre-Robertston-Walker Cosmological Model in an Inhomogeneous Universe: A Numerical Examination. AB - While the use of numerical general relativity for modeling astrophysical phenomena and compact objects is commonplace, the application to cosmological scenarios is only just beginning. Here, we examine the expansion of a spacetime using the Baumgarte-Shapiro-Shibata-Nakamura formalism of numerical relativity in synchronous gauge. This work represents the first numerical cosmological study that is fully relativistic, nonlinear, and without symmetry. The universe that emerges exhibits an average Friedmann-Lemaitre-Robertson-Walker (FLRW) behavior; however, this universe also exhibits locally inhomogeneous expansion beyond that expected in linear perturbation theory around a FLRW background. PMID- 27391711 TI - Effects of Nonlinear Inhomogeneity on the Cosmic Expansion with Numerical Relativity. AB - We construct a three-dimensional, fully relativistic numerical model of a universe filled with an inhomogeneous pressureless fluid, starting from initial data that represent a perturbation of the Einstein-de Sitter model. We then measure the departure of the average expansion rate with respect to this homogeneous and isotropic reference model, comparing local quantities to the predictions of linear perturbation theory. We find that collapsing perturbations reach the turnaround point much earlier than expected from the reference spherical top-hat collapse model and that the local deviation of the expansion rate from the homogeneous one can be as high as 28% at an underdensity, for an initial density contrast of 10^{-2}. We then study, for the first time, the exact behavior of the backreaction term Q_{D}. We find that, for small values of the initial perturbations, this term exhibits a 1/a scaling, and that it is negative with a linearly growing absolute value for larger perturbation amplitudes, thereby contributing to an overall deceleration of the expansion. Its magnitude, on the other hand, remains very small even for relatively large perturbations. PMID- 27391712 TI - Three-Dimensional Extended Bargmann Supergravity. AB - We show that three-dimensional general relativity, augmented with two vector fields, allows for a nonrelativistic limit, different from the standard limit leading to Newtonian gravity, that results in a well-defined action which is of the Chern-Simons type. We show that this three-dimensional "extended Bargmann gravity," after coupling to matter, leads to equations of motion allowing a wider class of background geometries than the ones that one encounters in Newtonian gravity. We give the supersymmetric generalization of these results and point out an important application in the context of calculating partition functions of nonrelativistic field theories using localization techniques. PMID- 27391713 TI - Shape Dependence of Holographic Renyi Entropy in Conformal Field Theories. AB - We develop a framework for studying the well-known universal term in the Renyi entropy for an arbitrary entangling region in four-dimensional conformal field theories that are holographically dual to gravitational theories. The shape dependence of the Renyi entropy S_{n} is described by two coefficients: f_{b}(n) for traceless extrinsic curvature deformations and f_{c}(n) for Weyl tensor deformations. We provide the first calculation of the coefficient f_{b}(n) in interacting theories by relating it to the stress tensor one-point function in a deformed hyperboloid background. The latter is then determined by a straightforward holographic calculation. Our results show that a previous conjecture f_{b}(n)=f_{c}(n), motivated by surprising evidence from a variety of free field theories and studies of conical defects, fails holographically. PMID- 27391714 TI - Lepton Flavor and Nonuniversality from Minimal Composite Higgs Setups. AB - We present a new class of models of lepton flavor in the composite Higgs framework. Following the concept of minimality, they lead to a rich phenomenology in good agreement with the current experimental picture. Because of a unification of the right-handed leptons, our scenario is very predictive and can naturally lead to a violation of lepton-flavor universality in neutral current interactions. We will show that, in particular, the anomaly in R_{K}=B(B >KMU^{+}MU^{-})/B(B->Ke^{+}e^{-}), found by LHCb, can be addressed, while other constraints from quark- and lepton-flavor physics are met. In fact, the minimal structure of the setup allows for the implementation of a very powerful flavor protection, which avoids the appearance of new sources of flavor-changing neutral currents to very good approximation. Finally, the new lepton sector provides a parametrically enhanced correction to the Higgs mass, such that the need for ultralight top partners is weakened considerably, linking the mass of the latter with the size of the neutrino masses. PMID- 27391716 TI - Proposed Inclusive Dark Photon Search at LHCb. AB - We propose an inclusive search for dark photons A^{'} at the LHCb experiment based on both prompt and displaced dimuon resonances. Because the couplings of the dark photon are inherited from the photon via kinetic mixing, the dark photon A^{'}->MU^{+}MU^{-} rate can be directly inferred from the off-shell photon gamma^{*}->MU^{+}MU^{-} rate, making this a fully data-driven search. For run 3 of the LHC, we estimate that LHCb will have sensitivity to large regions of the unexplored dark-photon parameter space, especially in the 210-520 MeV and 10-40 GeV mass ranges. This search leverages the excellent invariant-mass and vertex resolution of LHCb, along with its unique particle-identification and real-time data-analysis capabilities. PMID- 27391717 TI - Direct Evaluation of the Quark Content of Nucleons from Lattice QCD at the Physical Point. AB - We evaluate the light, strange, and charm scalar content of the nucleon using one lattice QCD ensemble generated with two degenerate light quarks with mass fixed to their physical value. We use improved techniques to evaluate the disconnected quark loops to sufficient accuracy to determine the strange and charm nucleon sigma terms in addition to the light quark content sigma_{piN}. We find sigma_{piN}=37.2(2.6)(4.7/2.9) MeV, sigma_{s}=41.1(8.2)(7.8/5.8) MeV, and sigma_{c}=79(21)(12/8) MeV, where the first error is statistical and the second is the systematic error due to the determination of the lattice spacing, the assessment of finite volume, and residual excited state effects. PMID- 27391718 TI - Event-by-Event Hydrodynamics+Jet Energy Loss: A Solution to the R_{AA}?v_{2} Puzzle. AB - High p_{T}>10 GeV elliptic flow, which is experimentally measured via the correlation between soft and hard hadrons, receives competing contributions from event-by-event fluctuations of the low-p_{T} elliptic flow and event-plane angle fluctuations in the soft sector. In this Letter, a proper account of these event by-event fluctuations in the soft sector, modeled via viscous hydrodynamics, is combined with a jet-energy-loss model to reveal that the positive contribution from low-p_{T} v_{2} fluctuations overwhelms the negative contributions from event-plane fluctuations. This leads to an enhancement of high-p_{T}>10 GeV elliptic flow in comparison to previous calculations and provides a natural solution to the decade-long high-p_{T} R_{AA}?v_{2} puzzle. We also present the first theoretical calculation of high-p_{T} v_{3}, which is shown to be compatible with current LHC data. Furthermore, we discuss how short-wavelength jet-medium physics can be deconvoluted from the physics of soft, bulk event-by event flow observables using event-shape engineering techniques. PMID- 27391719 TI - Surface Temperature Dependence of Hydrogen Ortho-Para Conversion on Amorphous Solid Water. AB - The surface temperature dependence of the ortho-to-para conversion of H_{2} on amorphous solid water is first reported. A combination of photostimulated desorption and resonance-enhanced multiphoton ionization techniques allowed us to sensitively probe the conversion on the surface of amorphous solid water at temperatures of 9.2-16 K. Within a narrow temperature window of 8 K, the conversion time steeply varied from ~4.1*10^{3} to ~6.4*10^{2} s. The observed temperature dependence is discussed in the context of previously suggested models and the energy dissipation process. The two-phonon process most likely dominates the conversion rate at low temperatures. PMID- 27391720 TI - Kinematics of Eley-Rideal Reactions at Hyperthermal Energies. AB - Direct or Eley-Rideal reactions between energetic N^{+} and O^{+} projectiles and O atoms, adsorbed onto Pt and Pd surfaces, are studied experimentally at incidence energies between 20 and 200 eV. The exit energies of the diatomic molecular products NO and O_{2} depend linearly on the incidence energy of the corresponding projectiles. A reaction mechanism is proposed, where the incident projectile collides with a single metal atom on the surface, linked to an adsorbed O atom. At the apsis point, a high-energy transient state is formed between the projectile, substrate, and adsorbate atoms. As the projectile begins to rebound, the transient state decomposes into a diatomic molecule, consisting of the original projectile and the adsorbed O atom, which exits the surface with memory of the incidence energy. Energy and momentum conservation during this single-bounce event (atom in, molecule out) accurately predict the exit energy of the molecular product, thus capturing the kinematics of the direct reaction. PMID- 27391721 TI - Interference at the Single Photon Level Along Satellite-Ground Channels. AB - Quantum interference arising from the superposition of states is striking evidence of the validity of quantum mechanics, confirmed in many experiments and also exploited in applications. However, as for any scientific theory, quantum mechanics is valid within the limits in which it has been experimentally verified. In order to extend such limits, it is necessary to observe quantum interference in unexplored conditions such as moving terminals at large distances in space. Here, we experimentally demonstrate single photon interference at a ground station due to the coherent superposition of two temporal modes reflected by a rapidly moving satellite a thousand kilometers away. The relative speed of the satellite induces a varying modulation in the interference pattern. The measurement of the satellite distance in real time by laser ranging allows us to precisely predict the instantaneous value of the interference phase. We then observed the interference patterns with a visibility up to 67% with three different satellites and with a path length up to 5000 km. Our results attest to the viability of photon temporal modes for fundamental tests of physics and quantum communication in space. PMID- 27391722 TI - Spatiotemporal Coherent Control of Light through a Multiple Scattering Medium with the Multispectral Transmission Matrix. AB - We report the broadband characterization of the propagation of light through a multiple scattering medium by means of its multispectral transmission matrix. Using a single spatial light modulator, our approach enables the full control of both the spatial and spectral properties of an ultrashort pulse transmitted through the medium. We demonstrate spatiotemporal focusing of the pulse at any arbitrary position and time with any desired spectral shape. Our approach opens new perspectives for fundamental studies of light-matter interaction in disordered media, and has potential applications in sensing, coherent control, and imaging. PMID- 27391723 TI - Reflective Spin-Orbit Geometric Phase from Chiral Anisotropic Optical Media. AB - We report on highly reflective spin-orbit geometric phase optical elements based on a helicity-preserving circular Bragg-reflection phenomenon. First, we present a dynamical geometric phase experiment using a flat chiral Bragg mirror. Then, we show that shaping such a geometric phase allows the efficient spin-orbit tailoring of light fields without the need to fulfill any condition on birefringent phase retardation, in contrast to the case of transmission spin orbit optical elements. This is illustrated by optical vortex generation from chiral liquid crystal droplets in the Bragg regime that unveils spin-orbit consequences of the droplet's curvature. Our results thus introduce a novel class of geometric phase elements-"Bragg-Berry" optical elements. PMID- 27391724 TI - Polychromatic Optical Vortex Generation from Patterned Cholesteric Liquid Crystals. AB - Generation of optical vortices is described in cholesteric liquid crystals with a singular point in the spatial distribution of a helix phase. The phenomenon uses the fact that a Bragg reflected light phase varies in proportion to the spatial phase of the helix, both at normal and oblique incidences. Our proposal enables high-efficiency, polychromatic generation of optical vortices without the need of a cumbersome fabrication process and fine-tuning. PMID- 27391725 TI - Localized Surface Plasmons Selectively Coupled to Resonant Light in Tubular Microcavities. AB - Vertical gold nanogaps are created on microtubular cavities to explore the coupling between resonant light supported by the microcavities and surface plasmons localized at the nanogaps. Selective coupling of optical axial modes and localized surface plasmons critically depends on the exact location of the gold nanogap on the microcavities, which is conveniently achieved by rolling up specially designed thin dielectric films into three-dimensional microtube cavities. The coupling phenomenon is explained by a modified quasipotential model based on perturbation theory. Our work reveals the coupling of surface plasmon resonances localized at the nanoscale to optical resonances confined in microtubular cavities at the microscale, implying a promising strategy for the investigation of light-matter interactions. PMID- 27391726 TI - Prediction and Control of Slip-Free Rotation States in Sphere Assemblies. AB - We study fixed assemblies of touching spheres that can individually rotate. From any initial state, sliding friction drives an assembly toward a slip-free rotation state. For bipartite assemblies, which have only even loops, this state has at least four degrees of freedom. For exactly four degrees of freedom, we analytically predict the final state, which we prove to be independent of the strength of sliding friction, from an arbitrary initial one. With a tabletop experiment, we show how to impose any slip-free rotation state by only controlling two spheres, regardless of the total number. PMID- 27391727 TI - Non-Negligible Diffusio-Osmosis Inside an Ion Concentration Polarization Layer. AB - The first experimental and theoretical evidence was provided for the non negligible role of a diffusio-osmosis in the ion concentration polarization (ICP) layer, which had been reported to be in a high Peclet number regime. Under the assumption that the hydrated shells of cations were stripped out with the amplified electric field inside the ICP layer, its concentration profile possessed a steep concentration gradient at the stripped location. Since the concentration gradient drove a strong diffusio-osmosis, the combination of electro-osmotic and diffusio-osmotic slip velocity had a form of an anomalous nonmonotonic function with both a single- and multiple-cationic solution. A direct measurement of electrolytic concentrations around the layer quantitatively validated our new investigations. This non-negligible diffusio-osmotic contribution in a micro- and nanofluidic platform or porous medium would be essential for clarifying the fundamental insight of nanoscale electrokinetics as well as guiding the engineering of ICP-based electrochemical systems. PMID- 27391728 TI - Optical Shaping of X-Ray Free-Electron Lasers. AB - In this Letter we report the experimental demonstration of a new temporal shaping technique for x-ray free-electron lasers (FELs). This technique is based on the use of a spectrally shaped infrared (IR) laser and allows optical control of the x-ray generation process. By accurately manipulating the spectral amplitude and phase of the IR laser, we can selectively modify the electron bunch longitudinal emittance thus controlling the duration of the resulting x-ray pulse down to the femtosecond time scale. Unlike other methods currently in use, optical shaping is directly applicable to the next generation of high-average power x-ray FELs such as the Linac Coherent Light Source-II or the European X-FEL, and it enables pulse shaping of FELs at the highest repetition rates. Furthermore, this laser-shaping technique paves the way for flexible tailoring of complex multicolor FEL pulse patterns required for nonlinear multidimensional x-ray spectroscopy as well as novel multicolor diffraction imaging schemes. PMID- 27391729 TI - Experimental Demonstration of the Collisionless Plasmoid Instability below the Ion Kinetic Scale during Magnetic Reconnection. AB - The spontaneous formation of magnetic islands is observed in driven, antiparallel magnetic reconnection on the Terrestrial Reconnection Experiment. We here provide direct experimental evidence that the plasmoid instability is active at the electron scale inside the ion diffusion region in a low collisional regime. The experiments show the island formation occurs at a smaller system size than predicted by extended magnetohydrodynamics or fully collisionless simulations. This more effective seeding of magnetic islands emphasizes their importance to reconnection in naturally occurring 3D plasmas. PMID- 27391730 TI - Experimental Observation and Computational Analysis of Striations in Electronegative Capacitively Coupled Radio-Frequency Plasmas. AB - Self-organized spatial structures in the light emission from the ion-ion capacitive rf plasma of a strongly electronegative gas (CF_{4}) are observed experimentally for the first time. Their formation is analyzed and understood based on particle-based kinetic simulations. These "striations" are found to be generated by the resonance between the driving radio frequency and the eigenfrequency of the ion-ion plasma (derived from an analytical model) that establishes a modulation of the electric field, the ion densities, as well as the energy gain and loss processes of electrons in the plasma. The growth of the instability is followed by the numerical simulations. PMID- 27391731 TI - Low Fuel Convergence Path to Direct-Drive Fusion Ignition. AB - A new class of inertial fusion capsules is presented that combines multishell targets with laser direct drive at low intensity (2.8*10^{14} W/cm^{2}) to achieve robust ignition. The targets consist of three concentric, heavy, metal shells, enclosing a volume of tens of MUg of liquid deuterium-tritium fuel. Ignition is designed to occur well "upstream" from stagnation, with minimal pusher deceleration to mitigate interface Rayleigh-Taylor growth. Laser intensities below thresholds for laser plasma instability and cross beam energy transfer facilitate high hydrodynamic efficiency (~10%). PMID- 27391732 TI - Constraining Solar Wind Heating Processes by Kinetic Properties of Heavy Ions. AB - We analyze the heavy ion components (A>4 amu) in collisionally young solar wind plasma and show that there is a clear, stable dependence of temperature on mass, probably reflecting the conditions in the solar corona. We consider both linear and power law forms for the dependence and find that a simple linear fit of the form T_{i}/T_{p}=(1.35+/-.02)m_{i}/m_{p} describes the observations twice as well as the equivalent best fit power law of the form T_{i}/T_{p}=(m_{i}/m_{p})^{1.07+/-.01}. Most importantly we find that current model predictions based on turbulent transport and kinetic dissipation are in agreement with observed nonthermal heating in intermediate collisional age plasma for m/q<3.5, but are not in quantitative or qualitative agreement with the lowest collisional age results. These dependencies provide new constraints on the physics of ion heating in multispecies plasmas, along with predictions to be tested by the upcoming Solar Probe Plus and Solar Orbiter missions to the near Sun environment. PMID- 27391733 TI - Optical Properties of Fluid Hydrogen at the Transition to a Conducting State. AB - We use fast transient transmission and emission spectroscopies in the pulse laser heated diamond anvil cell to probe the energy-dependent optical properties of hydrogen at pressures of 10-150 GPa and temperatures up to 6000 K. Hydrogen is absorptive at visible to near-infrared wavelengths above a threshold temperature that decreases from 3000 K at 18 GPa to 1700 K at 110 GPa. Transmission spectra at 2400 K and 141 GPa indicate that the absorptive hydrogen is semiconducting or semimetallic in character, definitively ruling out a first-order insulator-metal transition in the studied pressure range. PMID- 27391734 TI - Transport Properties of Metallic Ruthenates: A DFT+DMFT Investigation. AB - We present a systematical theoretical study on the transport properties of an archetypal family of Hund's metals, Sr_{2}RuO_{4}, Sr_{3}Ru_{2}O_{7}, SrRuO_{3}, and CaRuO_{3}, within the combination of first principles density functional theory and dynamical mean field theory. The agreement between theory and experiments for optical conductivity and resistivity is good, which indicates that electron-electron scattering dominates the transport of ruthenates. We demonstrate that in the single-site dynamical mean field approach the transport properties of Hund's metals fall into the scenario of "resilient quasiparticles." We explain why the single layered compound Sr_{2}RuO_{4} has a relative weak correlation with respect to its siblings, which corroborates its good metallicity. PMID- 27391735 TI - Photoinduced Demagnetization and Insulator-to-Metal Transition in Ferromagnetic Insulating BaFeO_{3} Thin Films. AB - We studied the electronic and magnetic dynamics of ferromagnetic insulating BaFeO_{3} thin films by using pump-probe time-resolved resonant x-ray reflectivity at the Fe 2p edge. By changing the excitation density, we found two distinctly different types of demagnetization with a clear threshold behavior. We assigned the demagnetization change from slow (~150 ps) to fast (<70 ps) to a transition into a metallic state induced by laser excitation. These results provide a novel approach for locally tuning magnetic dynamics. In analogy to heat assisted magnetic recording, metallization can locally tune the susceptibility for magnetic manipulation, allowing one to spatially encode magnetic information. PMID- 27391715 TI - Observation of h_{c} Radiative Decay h_{c}->gammaeta^{'} and Evidence for h_{c} >gammaeta. AB - A search for radiative decays of the P-wave spin singlet charmonium resonance h_{c} is performed based on 4.48*10^{8} psi^{'} events collected with the BESIII detector operating at the BEPCII storage ring. Events of the reaction channels h_{c}->gammaeta^{'} and gammaeta are observed with a statistical significance of 8.4sigma and 4.0sigma, respectively, for the first time. The branching fractions of h_{c}->gammaeta^{'} and h_{c}->gammaeta are measured to be B(h_{c} >gammaeta^{'})=(1.52+/-0.27+/-0.29)*10^{-3} and B(h_{c}->gammaeta)=(4.7+/-1.5+/ 1.4)*10^{-4}, respectively, where the first errors are statistical and the second are systematic uncertainties. PMID- 27391736 TI - Spontaneous Spin Textures in Multiorbital Mott Systems. AB - Spin textures in k-space arising from spin-orbit coupling in noncentrosymmetric crystals find numerous applications in spintronics. We present a mechanism that leads to the appearance of k-space spin texture due to spontaneous symmetry breaking driven by electronic correlations. Using dynamical mean-field theory we show that doping a spin-triplet excitonic insulator provides a means of creating new thermodynamic phases with unique properties. The numerical results are interpreted using analytic calculations within a generalized double-exchange framework. PMID- 27391737 TI - Predicted Quantum Topological Hall Effect and Noncoplanar Antiferromagnetism in K_{0.5}RhO_{2}. AB - The quantum anomalous Hall (QAH) phase is a two-dimensional bulk ferromagnetic insulator with a nonzero Chern number in the presence of spin-orbit coupling (SOC) but in the absence of applied magnetic fields. Associated metallic chiral edge states host dissipationless current transport in electronic devices. This intriguing QAH phase has recently been observed in magnetic impurity-doped topological insulators, albeit, at extremely low temperatures. Based on first principles density functional calculations, here we predict that layered rhodium oxide K_{0.5}RhO_{2} in the noncoplanar chiral antiferromagnetic state is an unconventional three-dimensional QAH insulator with a large band gap and a Neel temperature of a few tens of Kelvins. Furthermore, this unconventional QAH phase is revealed to be the exotic quantum topological Hall effect caused by nonzero scalar spin chirality due to the topological spin structure in the system and without the need of net magnetization and SOC. PMID- 27391738 TI - Spectroscopy and Dynamics of a Two-Dimensional Electron Gas on Ultrathin Helium Films on Cu(111). AB - Electrons in image-potential states on the surface of bulk helium represent a unique model system of a two-dimensional electron gas. Here, we investigate their properties in the extreme case of reduced film thickness: a monolayer of helium physisorbed on a single-crystalline (111)-oriented Cu surface. For this purpose we have utilized a customized setup for time-resolved two-photon photoemission at very low temperatures under ultrahigh vacuum conditions. We demonstrate that the highly polarizable metal substrate increases the binding energy of the first (n=1) image-potential state by more than 2 orders of magnitude as compared to the surface of liquid helium. An electron in this state is still strongly decoupled from the metal surface due to the large negative electron affinity of helium and we find that even 1 monolayer of helium increases its lifetime by 1 order of magnitude compared to the bare Cu(111) surface. PMID- 27391739 TI - Observation of the D'yakonov-Perel' Spin Relaxation in Single-Crystalline Pt Thin Films. AB - The spin relaxation mechanism in single-crystalline and polycrystalline platinum (Pt) thin films is revealed by a quantum interference effect. Examining the relationship between the spin relaxation rate and momentum scattering rate by changing Pt thickness, we find that the spin relaxation rate of Pt strongly depends on both crystal structure and thickness even though the quality of material (Pt) is unchanged. In particular, the D'yakonov-Perel' mechanism is considered as a dominant mechanism under cases where scattering events are suppressed or the interface effect is not negligible. PMID- 27391740 TI - Devil's Staircase Phase Diagram of the Fractional Quantum Hall Effect in the Thin Torus Limit. AB - After more than three decades, the fractional quantum Hall effect still poses challenges to contemporary physics. Recent experiments point toward a fractal scenario for the Hall resistivity as a function of the magnetic field. Here, we consider the so-called thin-torus limit of the Hamiltonian describing interacting electrons in a strong magnetic field, restricted to the lowest Landau level, and we show that it can be mapped onto a one-dimensional lattice gas with repulsive interactions, with the magnetic field playing the role of the chemical potential. The statistical mechanics of such models leads us to interpret the sequence of Hall plateaux as a fractal phase diagram whose landscape shows a qualitative agreement with experiments. PMID- 27391742 TI - Z_{2} Invariance of Germanene on MoS_{2} from First Principles. AB - We present a low energy Hamiltonian generalized to describe how the energy bands of germanene (Ge[over -]) are modified by interaction with a substrate or a capping layer. The parameters that enter the Hamiltonian are determined from first-principles relativistic calculations for Ge[over -]|MoS_{2} bilayers and MoS_{2}|Ge[over -]|MoS_{2} trilayers and are used to determine the topological nature of the system. For the lowest energy, buckled germanene structure, the gap depends strongly on how germanene is oriented with respect to the MoS_{2} layer(s). Topologically nontrivial gaps for bilayers and trilayers can be almost as large as for a freestanding germanene layer. PMID- 27391741 TI - Structural and Electronic Properties of Germanene on MoS_{2}. AB - To date germanene has only been synthesized on metallic substrates. A metallic substrate is usually detrimental for the two-dimensional Dirac nature of germanene because the important electronic states near the Fermi level of germanene can hybridize with the electronic states of the metallic substrate. Here we report the successful synthesis of germanene on molybdenum disulfide (MoS_{2}), a band gap material. Preexisting defects in the MoS_{2} surface act as preferential nucleation sites for the germanene islands. The lattice constant of the germanene layer (3.8+/-0.2 A) is about 20% larger than the lattice constant of the MoS_{2} substrate (3.16 A). Scanning tunneling spectroscopy measurements and density functional theory calculations reveal that there are, besides the linearly dispersing bands at the K points, two parabolic bands that cross the Fermi level at the Gamma point. PMID- 27391743 TI - General Conditions for Proximity-Induced Odd-Frequency Superconductivity in Two Dimensional Electronic Systems. AB - We obtain the general conditions for the emergence of odd-frequency superconducting pairing in a two-dimensional (2D) electronic system proximity coupled to a superconductor, making minimal assumptions about both the 2D system and the superconductor. Using our general results we show that a simple heterostructure formed by a monolayer of a group VI transition metal dichalcogenide, such as molybdenum disulfide, and an s-wave superconductor with Rashba spin-orbit coupling exhibits odd-frequency superconducting pairing. Our results allow the identification of a new class of systems among van der Waals heterostructures in which odd-frequency superconductivity should be present. PMID- 27391744 TI - Aperiodic Weak Topological Superconductors. AB - Weak topological phases are usually described in terms of protection by the lattice translation symmetry. Their characterization explicitly relies on periodicity since weak invariants are expressed in terms of the momentum-space torus. We prove the compatibility of weak topological superconductors with aperiodic systems, such as quasicrystals. We go beyond usual descriptions of weak topological phases and introduce a novel, real-space formulation of the weak invariant, based on the Clifford pseudospectrum. A nontrivial value of this index implies a nontrivial bulk phase, which is robust against disorder and hosts localized zero-energy modes at the edge. Our recipe for determining the weak invariant is directly applicable to any finite-sized system, including disordered lattice models. This direct method enables a quantitative analysis of the level of disorder the topological protection can withstand. PMID- 27391745 TI - Majorana Zero Mode Detected with Spin Selective Andreev Reflection in the Vortex of a Topological Superconductor. AB - Recently, theory has predicted a Majorana zero mode (MZM) to induce spin selective Andreev reflection (SSAR), a novel magnetic property which can be used to detect the MZM. Here, spin-polarized scanning tunneling microscopy or spectroscopy has been applied to probe SSAR of MZMs in a topological superconductor of the Bi_{2}Te_{3}/NbSe_{2} heterostructure. The zero-bias peak of the tunneling differential conductance at the vortex center is observed substantially higher when the tip polarization and the external magnetic field are parallel rather than antiparallel to each other. This spin dependent tunneling effect provides direct evidence of MZM and reveals its magnetic property in addition to the zero energy modes. Our work will stimulate MZM research on these novel physical properties and, hence, is a step towards experimental study of their statistics and application in quantum computing. PMID- 27391746 TI - Spin-Lattice-Coupled Order in Heisenberg Antiferromagnets on the Pyrochlore Lattice. AB - Effects of local lattice distortions on the spin ordering are investigated for the antiferromagnetic classical Heisenberg model on the pyrochlore lattice. It is found by Monte Carlo simulations that the spin-lattice coupling (SLC) originating from site phonons induces a first-order transition into two different types of collinear magnetic ordered states. The state realized at the stronger SLC is cubic symmetric characterized by the magnetic (1/2,1/2,1/2) Bragg peaks, while that at the weaker SLC is tetragonal symmetric characterized by the (1,1,0) ones, each accompanied by the commensurate local lattice distortions. Experimental implications to chromium spinels are discussed. PMID- 27391748 TI - Emergent Interacting Spin Islands in a Depleted Strong-Leg Heisenberg Ladder. AB - Properties of the depleted Heisenberg spin ladder material series (C_{7}H_{10}N)_{2}Cu_{1-z}Zn_{z}Br_{4} have been studied by the combination of magnetic measurements and neutron spectroscopy. Disorder-induced degrees of freedom lead to a specific magnetic response, described in terms of emergent strongly interacting "spin island" objects. The structure and dynamics of the spin islands is studied by high-resolution inelastic neutron scattering. This allows us to determine their spatial shape and to observe their mutual interactions, manifested by strong spectral in-gap contributions. PMID- 27391747 TI - Itinerant and Localized Magnetization Dynamics in Antiferromagnetic Ho. AB - Using femtosecond time-resolved resonant magnetic x-ray diffraction at the Ho L_{3} absorption edge, we investigate the demagnetization dynamics in antiferromagnetically ordered metallic Ho after femtosecond optical excitation. Tuning the x-ray energy to the electric dipole (E1, 2p->5d) or quadrupole (E2, 2p >4f) transition allows us to selectively and independently study the spin dynamics of the itinerant 5d and localized 4f electronic subsystems via the suppression of the magnetic (2 1 3-tau) satellite peak. We find demagnetization time scales very similar to ferromagnetic 4f systems, suggesting that the loss of magnetic order occurs via a similar spin-flip process in both cases. The simultaneous demagnetization of both subsystems demonstrates strong intra-atomic 4f-5d exchange coupling. In addition, an ultrafast lattice contraction due to the release of magneto-striction leads to a transient shift of the magnetic satellite peak. PMID- 27391750 TI - Unconventional Superfluidity in Yttrium Iron Garnet Films. AB - We argue that the magnon condensate in yttrium iron garnet may display experimentally observable superfluidity at room temperature despite the 100 times dominance of the normal density over superfluid ones. The superfluidity has a more complicated nature than in known superfluids since the U(1) symmetry of the global phase shift is violated by the dipolar interaction leading to the exchange of spin moment between the condensate and the crystal lattice. It produces periodic inhomogeneity in the stationary superfluid flow. We discuss the manner of observation and possible applications of magnon superfluidity. It may strongly enhance the spin-torque effects and reduce the energy consumption of the magnonic devices. PMID- 27391749 TI - Anisotropic Exchange within Decoupled Tetrahedra in the Quantum Breathing Pyrochlore Ba_{3}Yb_{2}Zn_{5}O_{11}. AB - The low energy spin excitation spectrum of the breathing pyrochlore Ba_{3}Yb_{2}Zn_{5}O_{11} has been investigated with inelastic neutron scattering. Several nearly resolution limited modes with no observable dispersion are observed at 250 mK while, at elevated temperatures, transitions between excited levels become visible. To gain deeper insight, a theoretical model of isolated Yb^{3+} tetrahedra parametrized by four anisotropic exchange constants is constructed. The model reproduces the inelastic neutron scattering data, specific heat, and magnetic susceptibility with high fidelity. The fitted exchange parameters reveal a Heisenberg antiferromagnet with a very large Dzyaloshinskii Moriya interaction. Using this model, we predict the appearance of an unusual octupolar paramagnet at low temperatures and speculate on the development of intertetrahedron correlations. PMID- 27391751 TI - Screening Nuclear Field Fluctuations in Quantum Dots for Indistinguishable Photon Generation. AB - A semiconductor quantum dot can generate highly coherent and indistinguishable single photons. However, intrinsic semiconductor dephasing mechanisms can reduce the visibility of two-photon interference. For an electron in a quantum dot, a fundamental dephasing process is the hyperfine interaction with the nuclear spin bath. Here, we directly probe the consequence of the fluctuating nuclear spins on the elastic and inelastic scattered photon spectra from a resident electron in a single dot. We find the in-plane component of the nuclear Overhauser field leads to detuned Raman scattered photons, broadened over experimental time scales by field fluctuations, which are distinguishable from both the elastic and incoherent components of the resonance fluorescence. This significantly reduces two-photon interference visibility. However, we demonstrate successful screening of the nuclear spin noise, which enables the generation of coherent single photons that exhibit high visibility two-photon interference. PMID- 27391752 TI - Local Electrical Imaging of Tetragonal Domains and Field-Induced Ferroelectric Twin Walls in Conducting SrTiO_{3}. AB - We demonstrate electrical mapping of tetragonal domains and electric field induced twin walls in SrTiO_{3} as a function of temperature and gate bias utilizing the conducting LaAlO_{3}/SrTiO_{3} interface and low-temperature scanning electron microscopy. Conducting twin walls appear below 105 K, and new twin patterns are observed after thermal cycling through the transition or on electric field gating. The nature of the twin walls is confirmed by calculating their intersection angles for different substrate orientations. Numerous walls formed when a large side- or back-gate voltage is applied are identified as field induced ferroelectric twin walls in the paraelectric tetragonal matrix. The walls persist after switching off the electric field and on thermal cycling below 105 K. These observations point to a new type of ferroelectric functionality in SrTiO_{3}, which could be exploited together with magnetism and superconductivity in a multifunctional context. PMID- 27391753 TI - Self-Assembly of Cubes into 2D Hexagonal and Honeycomb Lattices by Hexapolar Capillary Interactions. AB - Particles adsorbed at a fluid-fluid interface induce capillary deformations that determine their orientations and generate mutual capillary interactions which drive them to assemble into 2D ordered structures. We numerically calculate, by energy minimization, the capillary deformations induced by adsorbed cubes for various Young's contact angles. First, we show that capillarity is crucial not only for quantitative, but also for qualitative predictions of equilibrium configurations of a single cube. For a Young's contact angle close to 90 degrees , we show that a single-adsorbed cube generates a hexapolar interface deformation with three rises and three depressions. Thanks to the threefold symmetry of this hexapole, strongly directional capillary interactions drive the cubes to self assemble into hexagonal or graphenelike honeycomb lattices. By a simple free energy model, we predict a density-temperature phase diagram in which both the honeycomb and hexagonal lattice phases are present as stable states. PMID- 27391754 TI - Role of the Membrane for Mechanosensing by Tethered Channels. AB - Biologically important membrane channels are gated by force at attached tethers. Here, we generically characterize the nontrivial interplay of force, membrane tension, and channel deformations that can affect gating. A central finding is that minute conical channel deformation under force leads to significant energy release during opening. We also calculate channel-channel interactions and show that they can amplify the force sensitivity of tethered channels. PMID- 27391755 TI - DNA Twist Stability Changes with Magnesium(2+) Concentration. AB - To understand DNA elasticity at high forces (F>30 pN), its helical nature must be taken into account, as a coupling between twist and stretch. The prevailing model, the wormlike chain, was previously extended to include this twist-stretch coupling. Motivated by DNA's charged nature, and the known effects of ionic charges on its elasticity, we set out to systematically measure the impact of buffer ionic conditions on twist-stretch coupling. After developing a robust fitting approach, we show, using our new data set, that DNA's helical twist is stabilized at high concentrations of the magnesium divalent cation. DNA's persistence length and stretch modulus are, on the other hand, relatively insensitive to the applied range of ionic strengths. PMID- 27391756 TI - Fluctuations in the Kinetics of Linear Protein Self-Assembly. AB - Biological systems are characterized by compartmentalization from the subcellular to the tissue level, and thus reactions in small volumes are ubiquitous in living systems. Under such conditions, statistical number fluctuations, which are commonly negligible in bulk reactions, can become dominant and lead to stochastic behavior. We present here a stochastic model of protein filament formation in small volumes. We show that two principal regimes emerge for the system behavior, a small fluctuation regime close to bulk behavior and a large fluctuation regime characterized by single rare events. Our analysis shows that in both regimes the reaction lag-time scales inversely with the system volume, unlike in bulk. Finally, we use our stochastic model to connect data from small-volume microdroplet experiments of amyloid formation to bulk aggregation rates, and show that digital analysis of an ensemble of protein aggregation reactions taking place under microconfinement provides an accurate measure of the rate of primary nucleation of protein aggregates, a process that has been challenging to quantify from conventional bulk experiments. PMID- 27391758 TI - Elasticity and Fluctuations of Frustrated Nanoribbons. AB - We derive a reduced quasi-one-dimensional theory of geometrically frustrated elastic ribbons. Expressed in terms of geometric properties alone, it applies to ribbons over a wide range of scales, allowing the study of their elastic equilibrium, as well as thermal fluctuations. We use the theory to account for the twisted-to-helical transition of ribbons with spontaneous negative curvature and the effect of fluctuations on the corresponding critical exponents. The persistence length of such ribbons changes nonmonotonically with the ribbon's width, dropping to zero at the transition. This and other statistical properties qualitatively differ from those of nonfrustrated fluctuating filaments. PMID- 27391757 TI - Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness. AB - Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene. The strength of the negative feedback is characterized by three parameters: the cooperativity in self-repression, the maximal expression rate of the transcription factor, and the apparent dissociation constant of the transcription factor binding to its own promoter. Analysis of the model shows that the target gene levels are robust to mutations in the transcription factor, and that the robustness improves as the degree of cooperativity in self-repression increases. The prediction is tested in the LexA transcriptional network of E. coli by altering cooperativity in self-repression and promoter strength. Indeed, we find robustness is correlated with the former. Considering the proposed importance of gene regulation in speciation, parameters governing a transcription factor's robustness to mutation may have significant influence on a cell or organism's capacity to evolve. PMID- 27391759 TI - Solving the Dynamic Correlation Problem of the Susceptible-Infected-Susceptible Model on Networks. AB - The susceptible-infected-susceptible (SIS) model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in network epidemiology is the dynamic correlations coming from that if one node is infected, then its neighbors are likely to be infected. By combining two theoretical approaches-the heterogeneous mean-field theory and the effective degree method-we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models. PMID- 27391760 TI - Mining Twitter to Assess the Public Perception of the "Internet of Things". AB - Social media analysis has shown tremendous potential to understand public's opinion on a wide variety of topics. In this paper, we have mined Twitter to understand the public's perception of the Internet of Things (IoT). We first generated the discussion trends of the IoT from multiple Twitter data sources and validated these trends with Google Trends. We then performed sentiment analysis to gain insights of the public's attitude towards the IoT. As anticipated, our analysis indicates that the public's perception of the IoT is predominantly positive. Further, through topic modeling, we learned that public tweets discussing the IoT were often focused on business and technology. However, the public has great concerns about privacy and security issues toward the IoT based on the frequent appearance of related terms. Nevertheless, no unexpected perceptions were identified through our analysis. Our analysis was challenged by the limited fraction of tweets relevant to our study. Also, the user demographics of Twitter users may not be strongly representative of the population of the general public. PMID- 27391762 TI - Web Alert: Microbial enhancement of agricultural crops: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. PMID- 27391761 TI - Effects of melatonin on follicular atresia and granulosa cell apoptosis in the porcine. AB - The accumulation of reactive oxygen species is detrimental to the health of the ovarian follicle. The protective, antioxidant properties of melatonin, an endogenous component of porcine follicular fluid, on apoptosis of granulosa cells were evaluated in this study. Porcine granulosa cells from medium-sized (3-5 mm), healthy follicles were cultured in serum-free conditions with melatonin (0, 0.01, 0.1, 1.0, 10, and 100 ng/mL) with or without its receptor antagonist, luzindole, followed by evaluation of apoptotic markers in the treated cells. Results revealed that endogenous, intrafollicular melatonin concentration decreased as follicular atresia progressed, whereas the percentage of apoptotic granulosa cells increased. Spontaneous apoptosis of granulosa cells, triggered by serum deprivation in vitro, was remarkably blocked by melatonin (1.0 ng/mL melatonin, 32.7 +/- 0.5%, vs. control, 47.0 +/- 1.0%; P < 0.05). Treatment with 1.0 ng/mL of melatonin also significantly elevated MT2, SOD1, and GPX4 while lowering FASL, CHOP, and GRP78 mRNA abundance compared to the untreated control. The anti apoptotic effect and some changes of apoptotic-relevant genes in granulosa cells invoked by melatonin supplementation were markedly blocked by luzindole, suggesting that melatonin could prevent the apoptosis of porcine granulosa cells during follicular atresia via its membrane receptors and its free-radical scavenging activity. These findings provide new insights into the regulatory mechanism of melatonin in follicular atresia-related functions. Mol. Reprod. Dev. 83: 692-700, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27391765 TI - Conformation Analysis of Ferrocene and Decamethylferrocene via Full-Potential Modeling of XANES and XAFS Spectra. AB - Recent high-accuracy X-ray absorption measurements of the sandwich organometallics ferrocene (Fc) and decamethylferrocene (DmFc) at temperatures close to liquid helium are compared with new full-potential modeling of X-ray absorption fine structure (XAFS) covering the near-edge region (XANES) and above up to k = 7 A(-1). The implementation of optimized calculations of the oscillatory part of the spectrum from the package FDMX allows detailed study of the spectra in regions of the photoelectron momentum most sensitive to differences in the molecular stereochemistry. For Fc and DmFc, this corresponds to the relative rotation of the cyclopentadienyl rings. When applied to high accuracy XAFS of Fc and DmFc, the FDMX theory gives clear evidence for the eclipsed conformation for Fc and the staggered conformation for DmFc for frozen solutions at ca. 15 K. This represents the first clear experimental assignment of the solution structures of Fc and DmFc and reveals the potential of high-accuracy XAFS for structural analysis. PMID- 27391763 TI - Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk. AB - Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=-0.0022 T/S-ratio; 95% CI: -0.0035, -0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; <=5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ~6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals. PMID- 27391764 TI - Benchtop and Animal Validation of a Projective Imaging System for Potential Use in Intraoperative Surgical Guidance. AB - We propose a projective navigation system for fluorescence imaging and image display in a natural mode of visual perception. The system consists of an excitation light source, a monochromatic charge coupled device (CCD) camera, a host computer, a projector, a proximity sensor and a Complementary metal-oxide semiconductor (CMOS) camera. With perspective transformation and calibration, our surgical navigation system is able to achieve an overall imaging speed higher than 60 frames per second, with a latency of 330 ms, a spatial sensitivity better than 0.5 mm in both vertical and horizontal directions, and a projection bias less than 1 mm. The technical feasibility of image-guided surgery is demonstrated in both agar-agar gel phantoms and an ex vivo chicken breast model embedding Indocyanine Green (ICG). The biological utility of the system is demonstrated in vivo in a classic model of ICG hepatic metabolism. Our benchtop, ex vivo and in vivo experiments demonstrate the clinical potential for intraoperative delineation of disease margin and image-guided resection surgery. PMID- 27391766 TI - Gastroesophageal reflux disease: recent advances and its association with sleep. AB - Gastroesophageal reflux disease (GERD) is prevalent in Asia as well as in Western countries. Sleep disturbance and breathing disorders during sleep are becoming increasingly prevalent, and they are commonly associated with GERD. The relationship between GERD and obstructive sleep apnea (OSA) is still questionable, and it has expanded to include Barrett's esophagus. Nocturnal gastroesophageal reflux (nGER) symptoms might be clinically important in the explanation of this association. The therapy for reflux symptoms has resulted in improved subjective sleep parameters and enhanced sleep quality, thus supporting a direct relationship between GERD and sleep disturbance. This review discusses the epidemiology of sleep disturbances in GERD patients; the causative relationship between GERD and OSA, even though it remains an area of controversy; and the possible role of nGER in sleep problems. It also provides an update on the current state of knowledge linking GERD and sleep. PMID- 27391767 TI - Amphotericin B Associated Pulmonary Complications in Chronic Granulomatous Disease Patients. PMID- 27391768 TI - Visible-Light-Promoted Oxidative [4 + 2] Cycloadditions of Aryl Silyl Enol Ethers. AB - Visible-light-promoted oxidative [4 + 2] cycloadditions of epsilon,3-unsaturated silyl enol ethers have been developed to efficiently and diastereoselectively construct polycyclic skeletons under mild conditions. The diastereoselectivities were dependent on the stereoconfiguration of silyl enol ether, substitutions on the link, as well as electric properties of substitutions on aryl rings. The intermediates could be trapped by TEMPO, oxygen or methanol. Mechanistic studies indicated the reaction was initiated by one-electron oxidation of the silyl enol ether. PMID- 27391769 TI - Molecular Design for Tailoring a Single-Source Precursor for Bismuth Ferrite. AB - Nearly phase-pure bismuth ferrite particles were formed by thermolysis of the single-source precursor [Cp(CO)2FeBi(OAc)2] (1) in octadecene at 245 degrees C, followed by subsequent calcination at 600 degrees C for 3 h. In contrast, the slightly modified compound [Cp(CO)2FeBi(O2C(t)Bu)2] (2) yielded only mixtures of different bismuth oxide phases, revealing the distinctive influence of molecular design in material synthesis. The chemical composition, morphology, and crystallinity of the resulting materials were investigated by X-ray diffraction, transmission electron microscopy, and energy-dispersive X-ray spectroscopy. In addition, the optical properties were investigated by Fourier transform infrared and UV-vis spectroscopies, showing a strong band gap absorption in the visible range at 590 nm (2.2 eV). The magnetic behavior was probed by vibrating-sample and superconducting quantum interference device magnetometry, as well as (57)Fe Mossbauer spectroscopy. PMID- 27391770 TI - Hypertensive disorders in primigravid black South African women: A one-year descriptive analysis. AB - OBJECTIVE: To describe the incidence and obstetric and perinatal outcomes in primigravid Black South Africans with hypertensive disorders of pregnancy (HDP). METHOD: All primigravidae who booked for antenatal care were followed up until hospital discharge. Relevant clinical and demographic data were collected in structured data forms. RESULTS: A total of 5860 primigravidae delivered during the study period. Of these, 731 had an HDP, giving an incidence of 12.5%. The diagnosis of gestational hypertension was made in 6.7% of all primigravidae but was the commonest HDP subcategory (n = 394/731; 53.9%). On the other hand, mild to moderate preeclampsia or non-severe preeclampsia, severe preeclampsia, and eclampsia occurred in 222, 84, and 31 of the 5860 primigravidae, respectively. Therefore, preeclampsia-eclampsia syndrome occurred in 337/5860 or 5.75% of the study population. Severe preeclampsia occurred in 1.43% (84/5860) of the primigravidae. The rates of caesarean deliveries in women with preeclampsia were approximately 50%. There were no perinatal deaths in the gestational hypertension group, but the overall perinatal mortality rate in all preeclamptics was 5.9%, in comparison to 2.2% in all primigravidae. CONCLUSION: Hypertensive disorders of pregnancy developed in 12.5% (n = 731/5860) of primigravidae seen over a one-year period. Gestational hypertension comprised the commonest subcategory of the HDP and there were no perinatal deaths in this group. PMID- 27391772 TI - [Not Available]. PMID- 27391773 TI - Early Clinical Experience with a Newly Designed Interlocking Nail System Targon((r)) Vet. AB - OBJECTIVE: To describe early clinical experience with a newly designed interlocking nail system (Targon((r)) Vet) in diaphyseal fractures in cats and small dogs. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned cats (n=49) and dogs (n=8). METHODS: Fifty-seven consecutive cases (49 cats, 8 dogs) with 60 long bone fractures were included in the study. Follow-up radiographs were scheduled at 4 and 8 weeks and again 6 months postoperatively. The end point for each case was determined radiographically by a healed fracture. Complications were defined as minor or major. Clinical outcome was subjectively assessed by a full orthopedic examination and follow-up radiographs. Descriptive data are reported. RESULTS: Median age of cats was 18 months (range, 3-220 months) and of dogs was 28 months (range, 7-115 months). Median body weight was 3.7 kg (range, 1.67-8.41 kg) for cats and 8.15 kg (range, 2.68-13.6 kg) for dogs. Median radiographic follow-up was 16 weeks. All fractures with follow-up radiographs available (n=46) were healed with no infections reported. A total of 12 postoperative complications occurred: 3 minor (slippage of the locking screws) and 9 major (5 femoral-irritation of the sciatic nerve, stress protection, fracture because of a missed fissure, femoral neck fracture, intra-operative revision with a rod and plate; 4 tibial-3 with protrusion of the distal locking screw through the skin and 1 with in-growth of the intramedullary nail). CONCLUSION: Implantation of the Targon((r)) Vet System was feasible in all cases. It provides an alternative system for diaphyseal fracture repair in cats and small dogs. PMID- 27391771 TI - Principles and management of neuropsychiatric symptoms in Alzheimer's dementia. AB - Neuropsychiatric symptoms of Alzheimer's disease (NPS-AD) are highly prevalent and lead to poor medical and functional outcomes. In spite of the burdensome nature of NPS-AD, we are continuing to refine the nosology and only beginning to understand the underlying pathophysiology. Cluster analyses have frequently identified three to five subsyndromes of NPS-AD: behavioral dysfunction (for example, agitation/aggressiveness), psychosis (for example, delusions and hallucinations), and mood disturbance (for example, depression or apathy). Recent neurobiological studies have used new neuroimaging techniques to elucidate behaviorally relevant circuits and networks associated with these subsyndromes. Several fronto-subcortical circuits, cortico-cortical networks, and neurotransmitter systems have been proposed as regions and mechanisms underlying NPS-AD. Common to most of these subsyndromes is the broad overlap of regions associated with the salience network (anterior cingulate and insula), mood regulation (amygdala), and motivated behavior (frontal cortex). Treatment strategies for dysregulated mood syndromes (depression and apathy) have primarily targeted serotonergic mechanisms with antidepressants or dopaminergic mechanisms with psychostimulants. Psychotic symptoms have largely been targeted with anti psychotic medications despite controversial risk/benefit tradeoffs. Management of behavioral dyscontrol, including agitation and aggression in AD, has encompassed a wide range of psychoactive medications as well as non-pharmacological approaches. Developing rational therapeutic approaches for NPS-AD will require a firmer understanding of the underlying etiology in order to improve nosology as well as provide the empirical evidence necessary to overcome regulatory and funding challenges to further study these debilitating symptoms. PMID- 27391776 TI - Confined, Oriented, and Electrically Anisotropic Graphene Wrinkles on Bacteria. AB - Curvature-induced dipole moment and orbital rehybridization in graphene wrinkles modify its electrical properties and induces transport anisotropy. Current wrinkling processes are based on contraction of the entire substrate and do not produce confined or directed wrinkles. Here we show that selective desiccation of a bacterium under impermeable and flexible graphene via a flap-valve operation produces axially aligned graphene wrinkles of wavelength 32.4-34.3 nm, consistent with modified Foppl-von Karman mechanics (confinement ~0.7 * 4 MUm(2)). Further, an electrophoretically oriented bacterial device with confined wrinkles aligned with van der Pauw electrodes was fabricated and exhibited an anisotropic transport barrier (DeltaE = 1.69 meV). Theoretical models were developed to describe the wrinkle formation mechanism. The results obtained show bio-induced production of confined, well-oriented, and electrically anisotropic graphene wrinkles, which can be applied in electronics, bioelectromechanics, and strain patterning. PMID- 27391775 TI - Dermoscopy of Melanomas on the Trunk and Extremities in Asians. AB - The incidence of melanoma among the Asian population is lower compared to that among the Western European population. These populations differed in their most common histopathologic subtypes, acral lentiginous melanoma being the most common in the Asian population. Although the dermoscopic features of the melanomas on the acral skin have been thoroughly investigated in the Asian population, studies concerning the dermoscopic patterns of melanomas on the non-acral skin have been scarce. The aim of this study was to investigate the dermoscopic patterns of melanomas on the trunk and extremities in the Asian population. To achieve this, we evaluated the dermoscopic patterns of 22 primary melanomas diagnosed at two university hospitals in Korea. In addition, 100 benign melanocytic lesions were included as the control group for comparative analysis. A P value less than 0.05 was regarded as statistically significant. Melanoma-associated dermoscopic features such as asymmetry (odds ratio [OR], 30.00), multicolor pattern (OR, 30.12), blotches (OR, 13.50), blue white veils (OR, 15.75), atypical pigment networks (OR, 9.71), irregular peripheral streaks (OR, 6.30), atypical vascular patterns (OR, 11.50), ulcers (OR, 15.83), atypical dots/globules (OR, 3.15), shiny white lines (OR, 5.88), and regression structures (OR, 7.06) were more commonly observed in patients with melanomas than in patients of the control group. The mean dermoscopic scores obtained on the 7-point checklist, revised 7 point checklist, 3-point checklist, ABCD rule, and CASH algorithm were 5.36, 3.41, 2.05, 6.89, and 9.68, respectively, in the primary melanomas, and 1.33, 0.93, 0.46, 2.45, and 3.60, respectively, in the control group (all, P < 0.001). The present study showed that melanoma-related dermoscopic patterns were common in Asian patients. Dermoscopy is a reliable diagnostic tool for the melanomas of the trunk and extremities in the Asian populations. PMID- 27391777 TI - Clinicopathological characteristics of systemic mastocytosis in the intestine. AB - AIMS: Gastrointestinal (GI) involvement by systemic mastocytosis (SM) presents with non-specific symptoms, and pathological diagnosis can be difficult when a subtle mast cell infiltrate is present. The aim of this study was to characterize the clinicopathological features in diagnostically challenging cases. METHODS AND RESULTS: Seven patients with GI biopsies showing an atypical mast cell infiltrate were identified, including three consultation cases in which mast cells were initially overlooked. Clinicopathological characteristics were evaluated. Biopsies showed involvement of the large bowel (n = 5), small bowel (n = 1) or both (n = 1) by a wide morphological spectrum of mast cells, including: bland spindle cells; small cells with irregular nuclei; and medium-sized monotonous cells with abundant pale cytoplasm. The patterns of mucosal involvement included: a polypoid mast cell aggregate (n = 1); a confluent subepithelial band of mast cells (n = 3); and multifocal aggregates of mast cells (n = 3). There were admixed eosinophils with a noticeable lack of plasma cells. Mast cells in all cases showed strong positive staining for CD117 and CD25. All patients fulfilled the World Health Organization (WHO) criteria for SM. On follow-up in four cases, none had progression of disease. CONCLUSIONS: Atypical mast cell infiltrates in the intestine are often subtle and can easily be overlooked. Clues to diagnosis include lamina propria expansion by monotonous cells with pale cytoplasm, admixed eosinophils, and the absence of crypt distortion or significant plasmacytic infiltrate. Although most patients with GI involvement by SM are symptomatic, a subset remain asymptomatic, and the absence of clinical suspicion of mast cell disease adds to the difficulty in making a diagnosis of SM. PMID- 27391774 TI - Design and methods of CYCLE-HD: improving cardiovascular health in patients with end stage renal disease using a structured programme of exercise: a randomised control trial. AB - BACKGROUND: There is emerging evidence that exercise training could positively impact several of the cardiovascular risk factors associated with sudden cardiac death amongst patients on haemodialysis. The primary aim of this study is to evaluate the effect of an intradialytic exercise programme on left ventricular mass. METHOD AND DESIGN: Prospective, randomised cluster open-label blinded endpoint clinical trial in 130 patients with end stage renal disease on haemodialysis. Patients will be randomised 1:1 to either 1) minimum of 30 min continuous cycling thrice weekly during dialysis or 2) standard care. The primary outcome is change in left ventricular mass at 6 months, assessed by cardiac MRI (CMR). In order to detect a difference in LV mass of 15 g between groups at 80 % power, a sample size of 65 patients per group is required. Secondary outcome measures include abnormalities of cardiac rhythm, left ventricular volumes and ejection fraction, physical function measures, anthropometric measures, quality of life and markers of inflammation, with interim assessment for some measures at 3 months. DISCUSSION: This study will test the hypothesis that an intradialytic programme of exercise leads to a regression in left ventricular mass, an important non-traditional cardiovascular risk factor in end stage renal disease. For the first time this will be assessed using CMR. We will also evaluate the efficacy, feasibility and safety of an intradialytic exercise programme using a number of secondary end-points. We anticipate that a positive outcome will lead to both an increased patient uptake into established intradialytic programmes and the development of new programmes nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN11299707 (registration date 5(th) March 2015). PMID- 27391778 TI - Autophagy and Mitochondrial Dysfunction in Tenon Fibroblasts from Exfoliation Glaucoma Patients. AB - PURPOSE: To test the hypothesis that autophagy dysfunction is involved in exfoliation syndrome (XFS), a systemic disorder of extracellular elastic matrices that causes a distinct form of human glaucoma. METHODS: Fibroblasts derived from tenon tissue discards (TFs) from filtration surgery to relieve intraocular pressure in XFS patients were compared against age-matched TFs derived from surgery in primary open-angle glaucoma (POAG) patients or from strabismus surgery. Differential interference contrast light, and electron microscopy were used to examine structural cell features. Immunocytochemistry was used to visualize LOXL1 and Fibulin-5, lysosomes, endosomes, Golgi, and microtubules. Light scatter, Cyto-IDTM and JC1 flow cytometry were used to measure relative cell size, autophagic flux rate and mitochondrial membrane potential (MMPT), respectively. Enhanced autophagy was induced by serum withdrawal. RESULTS: In culture, XFS-TFs were 1.38-fold larger (by light scatter ratio, p = 0.05), proliferated 42% slower (p = 0.026), and were morphologically distinct in 2D and 3D culture compared to their POAG counterparts. In extended 3D cultures, XFS-TFs accumulated 8-10 times more Fibulin-5 than the POAG-TFs, and upon serum withdrawal, there were marked deficiencies in relocation of endosomes and lysosomes to the perinuclear area. Correspondingly, the XFS-TFs displayed significant accumulation of the autophagasome marker LC3 II (3.9 fold increase compared to POAG levels, p = 0.0001) and autophagic flux rate as measured by Cyto ID dye was 53% lower in XFS-TFs than in POAG-TFs (p = 0.01), indicating reduced clearance of autophagasomes. Finally the percent of cells with diminished MMPT was 3-8 times larger in the XFS-TFs than in POAG-TFs (p = 0.02). CONCLUSIONS: Our results provide for the first time a link between XFS pathology to autophagy dysfunction, a major contributor to multiple age related diseases systemically throughout the body, in the brain and in the retina. A diminished capacity for degradation of denatured protein and aging cellular organelles may underpin the development of extracellular protein aggregates in XFS. PMID- 27391779 TI - Task Prioritization in Dual-Tasking: Instructions versus Preferences. AB - The role of task prioritization in performance tradeoffs during multi-tasking has received widespread attention. However, little is known on whether people have preferences regarding tasks, and if so, whether these preferences conflict with priority instructions. Three experiments were conducted with a high-speed driving game and an auditory memory task. In Experiment 1, participants did not receive priority instructions. Participants performed different sequences of single-task and dual-task conditions. Task performance was evaluated according to participants' retrospective accounts on preferences. These preferences were reformulated as priority instructions in Experiments 2 and 3. The results showed that people differ in their preferences regarding task prioritization in an experimental setting, which can be overruled by priority instructions, but only after increased dual-task exposure. Additional measures of mental effort showed that performance tradeoffs had an impact on mental effort. The interpretation of these findings was used to explore an extension of Threaded Cognition Theory with Hockey's Compensatory Control Model. PMID- 27391780 TI - Digital image modification detection using color information and its histograms. AB - The rapid development of many open source and commercial image editing software makes the authenticity of the digital images questionable. Copy-move forgery is one of the most widely used tampering techniques to create desirable objects or conceal undesirable objects in a scene. Existing techniques reported in the literature to detect such tampering aim to improve the robustness of these methods against the use of JPEG compression, blurring, noise, or other types of post processing operations. These post processing operations are frequently used with the intention to conceal tampering and reduce tampering clues. A robust method based on the color moments and other five image descriptors is proposed in this paper. The method divides the image into fixed size overlapping blocks. Clustering operation divides entire search space into smaller pieces with similar color distribution. Blocks from the tampered regions will reside within the same cluster since both copied and moved regions have similar color distributions. Five image descriptors are used to extract block features, which makes the method more robust to post processing operations. An ensemble of deep compositional pattern-producing neural networks are trained with these extracted features. Similarity among feature vectors in clusters indicates possible forged regions. Experimental results show that the proposed method can detect copy-move forgery even if an image was distorted by gamma correction, addictive white Gaussian noise, JPEG compression, or blurring. PMID- 27391781 TI - Parenting style, resilience, and mental health of community-dwelling elderly adults in China. AB - BACKGROUND: Given the increasing elderly population worldwide, the identification of potential determinants of successful ageing is important. Many studies have shown that parenting style and mental resilience may influence mental health; however, little is known about the psychological mechanisms that underpin this relationship. The current study sought to explore the relationships among mental resilience, perceptions of parents' parenting style, and depression and anxiety among community-dwelling elderly adults in China. METHODS: In total, 439 community-dwelling elderly Chinese adults aged 60-91 years completed the Personal and Parents' Parenting Style Scale, Connor-Davidson Resilience Scale, Zung Self Rating Depression Scale, and Zung Self-Rating Anxiety Scale. RESULTS: Elderly adults whose parents preferred positive and authoritative parenting styles had higher levels of mental resilience and lower levels of depression and anxiety. Elderly adults parented in the authoritarian style were found to have higher levels of depression and anxiety, with lower mental resilience. CONCLUSIONS: The findings of this study provide evidence related to successful ageing and coping with life pressures, and highlight the important effects of parenting on mental health. The results suggest that examination of the proximal determinants of successful ageing is not sufficient-distal factors may also contribute to the 'success' of ageing by modifying key psychological dispositions that promote adaptation to adversity. PMID- 27391783 TI - Overestimated value of FDG-PET based bone marrow evaluation in lymphoma: Response to Adams and Kwee. PMID- 27391784 TI - Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma. AB - The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma-a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein-display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1 deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers. PMID- 27391786 TI - Analysis of Network Clustering Algorithms and Cluster Quality Metrics at Scale. AB - OVERVIEW: Notions of community quality underlie the clustering of networks. While studies surrounding network clustering are increasingly common, a precise understanding of the realtionship between different cluster quality metrics is unknown. In this paper, we examine the relationship between stand-alone cluster quality metrics and information recovery metrics through a rigorous analysis of four widely-used network clustering algorithms-Louvain, Infomap, label propagation, and smart local moving. We consider the stand-alone quality metrics of modularity, conductance, and coverage, and we consider the information recovery metrics of adjusted Rand score, normalized mutual information, and a variant of normalized mutual information used in previous work. Our study includes both synthetic graphs and empirical data sets of sizes varying from 1,000 to 1,000,000 nodes. CLUSTER QUALITY METRICS: We find significant differences among the results of the different cluster quality metrics. For example, clustering algorithms can return a value of 0.4 out of 1 on modularity but score 0 out of 1 on information recovery. We find conductance, though imperfect, to be the stand-alone quality metric that best indicates performance on the information recovery metrics. Additionally, our study shows that the variant of normalized mutual information used in previous work cannot be assumed to differ only slightly from traditional normalized mutual information. NETWORK CLUSTERING ALGORITHMS: Smart local moving is the overall best performing algorithm in our study, but discrepancies between cluster evaluation metrics prevent us from declaring it an absolutely superior algorithm. Interestingly, Louvain performed better than Infomap in nearly all the tests in our study, contradicting the results of previous work in which Infomap was superior to Louvain. We find that although label propagation performs poorly when clusters are less clearly defined, it scales efficiently and accurately to large graphs with well-defined clusters. PMID- 27391785 TI - Expression Patterns of Three UGT Genes in Different Chemotype Safflower Lines and under MeJA Stimulus Revealed Their Potential Role in Flavonoid Biosynthesis. AB - Safflower (Carthamus tinctorius L.) has received a significant amount of attention as a medicinal plant in China. Flavonoids are the dominant active medical compounds. UDP-glycosyltransferase plays an essential role in the biosynthesis and storage of flavonoids in safflower. In this study, 45 UGT unigenes were screened from our transcriptomic database of safflower. Among them, 27 UGT unigenes were predicted to own a complete open reading frame with various pI and Mw. The phylogenetic tree showed that CtUGT3 and CtUGT16 were classified under the UGT71 subfamily involved in metabolite process, whereas CtUGT25 has high identities with PoUGT both catalyzing the glycosylation of flavonoids and belonging to the UGT90 subfamily. cDNA microarray exhibited that the three UGT genes displayed temporal difference in two chemotype safflower lines. To functionally characterize UGT in safflower, CtUGT3, CtUGT16 and CtUGT25 were cloned and analyzed. Subcellular localization suggested that the three UGTs might be located in the cell cytoplasm and chloroplast. The expression pattern showed that the three UGTs were all suppressed in two lines responsive to methyl jasmonate induction. The co-expression relation of expression pattern and metabolite accumulation demonstrated that CtUGT3 and CtUGT25 were positively related to kaempferol-3-O-beta-D-glucoside and CtUGT16 was positively related to quercetin-3-O-beta-D-glucoside in yellow line, whereas CtUGT3 and CtUGT25 were positively related to quercetin-3-O-beta-D-glucoside in white line. This study indicates that the three CtUGTs play a significant and multiple role in flavonoids biosynthesis with presenting different functional characterization in two safflower lines. PMID- 27391787 TI - The Effect of Diet Mixing on a Nonselective Herbivore. AB - The balanced-diet hypothesis states that a diverse prey community is beneficial to consumers due to resource complementarity among the prey species. Nonselective consumer species cannot differentiate between prey items and are therefore not able to actively regulate their diet intake. We thus wanted to test whether the balanced-diet hypothesis is applicable to nonselective consumers. We conducted a laboratory experiment in which a nonselective model grazer, the freshwater gastropod Lymnaea stagnalis, was fed benthic green algae as single species or as a multi-species mixture and quantified the snails' somatic growth rates and shell lengths over a seven-week period. Gastropods fed the mixed diet were found to exhibit a higher somatic growth rate than the average of the snails fed single prey species. However, growth on the multi-species mixture did not exceed the growth rate obtained on the best single prey species. Similar results were obtained regarding the animals' shell height increase over time. The mixed diet did not provide the highest growth rate, which confirms our hypothesis. We thus suggest that the balanced-diet hypothesis is less relevant for non-selective generalist consumers, which needs to be considered in estimates of secondary production. PMID- 27391788 TI - Copying the development: mirror neurons in child development. AB - Since intrauterine life, our brain is exposed to diverse internal and external factors that generate epigenetic changes affecting the neural networks and thus modifying the properties of the mirror neurons of the developing infant. We consider that changes on the mirror neurons may play a role on the neuro developmental pathologies of an infant where no structural brain lesion is observed. PMID- 27391789 TI - Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids. AB - Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide-lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions. PMID- 27391790 TI - Adaptation in protein fitness landscapes is facilitated by indirect paths. AB - The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20(L)) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 20(4) = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. PMID- 27391792 TI - Lewis Acid Catalyzed Selective Reactions of Donor-Acceptor Cyclopropanes with 2 Naphthols. AB - Lewis acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with 2-naphthols is reported. The reaction exhibits tunable selectivity depending on the nature of Lewis acid employed and proceed as a dearomatization/rearomatization sequence. With Bi(OTf)3 as the Lewis acid, a highly selective dehydrative [3+2] cyclopentannulation takes place leading to the formation of naphthalene-fused cyclopentanes. Interestingly, engaging Sc(OTf)3 as the Lewis acid, a Friedel-Crafts-type addition of 2-naphthols to cyclopropanes takes place, thus affording functionalized 2-naphthols. Both reactions furnished the target products in high regioselectivity and moderate to high yields. PMID- 27391791 TI - Mediators of the relationship between thin-ideal internalization and body dissatisfaction in the natural environment. AB - Social comparisons (i.e., body, eating, exercise) and body surveillance were tested as mediators of the thin-ideal internalization-body dissatisfaction relationship using ecological momentary assessment (EMA). Participants were 232 college women who completed a 2-week EMA protocol, responding to questions three times per day. Multilevel path analysis was used to examine a 2-1-1 mediation model (thin-ideal internalization assessed as trait; between-person effects examined) and a 1-1-1 model (component of thin-ideal internalization [thin-ideal importance] assessed momentarily; within- and between-person effects examined). For the 2-1-1 model, only body comparison and body surveillance were significant specific mediators of the between-person effect. For the 1-1-1 model, all four variables were significant specific mediators of the within-person effect. Only body comparison was a significant specific mediator of the between-person effect. At the state level, many processes explain the thin-ideal internalization-body dissatisfaction relationship. However, at the trait level, body comparison and body surveillance are more important explanatory factors. PMID- 27391793 TI - lincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through Notch signaling-induced epithelial-mesenchymal transition. AB - AIM: Emerging evidence has showed that long non-coding RNA (lncRNA) play an important role in the occurrence and development of various cancers. In the present study, the expression level of lincRNA-p21 was investigated in hepatocellular carcinoma (HCC), and its role in invasion of HCC was also explored. METHODS: The lincRNA-p21 levels in human HCC tumor tissue and cell lines HepG2 and SMMC-7721 were determined by real-time polymerase chain reaction. Transfected HCC cells with pcDNA-lincRNA-p21 or si-lincRNA-p21 for overexpression or downregulation of lincRNA-p21, the Notch signaling and epithelial-mesenchymal transition (EMT)-related proteins and cell invasion were measured by western blot and Transwell assay, respectively. A tumor xenotransplant mouse model was also established to investigate the role of lincRNA-p21 in tumor metastasis in vivo. RESULTS: The lincRNA-p21 expression was downregulated in HCC tissue and cells. Overexpression of lincRNA-p21 inhibited Notch singling and EMT, while its downregulation led to the reverse result. The invasion of HCC cell was also inhibited by pcDNA-lincRNA-p21, and activation of Notch signaling reversed this effect. In vivo, overexpression of lincRNA-p21 decreased the tumor metastasis, as well. CONCLUSION: lincRNA-p21 was downregulated in HCC and lincRNA-p21 overexpression contributed to the inhibition of tumor invasion through mediating Notch signaling induced EMT. PMID- 27391794 TI - Roles of Cell Cyle Regulators Cyclin D1, CDK4, and p53 in Knee Osteoarthritis. AB - OBJECTIVE: The aim of this study was to investigate the roles of cyclin D1, CDK4, and p53 in knee osteoarthritis (KOA). METHODS: A total of 76 healthy controls and 154 KOA cases (grades ranging from II to IV) were recruited. Protein expression of cyclin D1, CDK4, and p53 were detected by immunohistochemistry, and mRNA expression levels of the cyclin D1, the CDK4, and the p53 genes were measured by reverse transcription-polymerase chain reaction. RESULTS: Both protein and mRNA expression levels of cyclin D1 and CDK4 were significantly lower in KOA cases than those in healthy controls, while protein and mRNA expression of p53 was significantly higher in KOA cases than that in healthy controls (all p < 0.05). As the grades of KOA increased, Cyclin D1 and CDK4 mRNA expressions decreased, whereas p53 mRNA expression increased (all p < 0.05). In KOA cases, mRNA expression of Cyclin D1 was positively correlated to CDK4 mRNA levels (r = 0.386, p < 0.001), while negatively correlated with p53 mRNA levels (r = -0.227, p = 0.005). CONCLUSIONS: Expression of the Cyclin D1, CDK4, and p53 genes are correlated with the disease grades of KOA. PMID- 27391795 TI - Effects of cigarette smoking on ambulatory blood pressure, heart rate, and heart rate variability in treated hypertensive patients. AB - We investigated the influence of cigarette smoking on the levels and circadian patterns of blood pressure (BP), heart rate (HR), and HR variability (HRV) in hypertensive patients. Sixteen hypertensive smokers (57 +/- 2 years old) receiving antihypertensive treatments participated in this study. Ambulatory monitoring of BP, HR, and electrocardiograms was performed every 30 min for 24 hours on a smoking day and nonsmoking day in a randomized crossover manner. Average 24-hour BP and daytime BP were significantly higher in the smoking period than in the nonsmoking period. No significant differences were observed in nighttime BP between the two periods. Average 24-hour and daytime HR, but not nighttime HR, were also higher in the smoking period than in the nonsmoking period. The daytime high frequency (HF) component of HRV was attenuated more in the smoking period than in the nonsmoking period. No significant differences were observed in the low frequency (LF) components of HRV or LF/HF ratio between the two periods. These results demonstrated that cigarette smoking increased the daytime and average 24-hour BP and HR, and the increases observed in daytime BP and HR were associated with the attenuation of parasympathetic nerve activity. PMID- 27391796 TI - Using Quasi-Horizontal Alignment in the absence of the actual alignment. AB - Horizontal alignment is a major roadway characteristic used in safety and operational evaluations of many facility types. The Highway Safety Manual (HSM) uses this characteristic in crash prediction models for rural two-lane highways, freeway segments, and freeway ramps/C-D roads. Traffic simulation models use this characteristic in their processes on almost all types of facilities. However, a good portion of roadway databases do not include horizontal alignment data; instead, many contain point coordinate data along the roadways. SHRP 2 Roadway Information Database (RID) is a good example of this type of data. Only about 5% of this geodatabase contains alignment information and for the rest, point data can easily be produced. Even though the point data can be used to extract actual horizontal alignment data but, extracting horizontal alignment is a cumbersome and costly process, especially for a database of miles and miles of highways. This research introduces a so called "Quasi-Horizontal Alignment" that can be produced easily and automatically from point coordinate data and can be used in the safety and operational evaluations of highways. SHRP 2 RID for rural two-lane highways in Washington State is used in this study. This paper presents a process through which Quasi-Horizontal Alignments are produced from point coordinates along highways by using spreadsheet software such as MS EXCEL. It is shown that the safety and operational evaluations of the highways with Quasi-Horizontal Alignments are almost identical to the ones with the actual alignments. In the absence of actual alignment the Quasi-Horizontal Alignment can easily be produced from any type of databases that contain highway coordinates such geodatabases and digital maps. PMID- 27391797 TI - Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans. AB - Failing to repair DNA double-strand breaks by either nonhomologous end joining (NHEJ) or homologous recombination (HR) poses a threat to genome integrity, and may have roles in the onset of aging and age-related diseases. Recent work indicates an age-related decrease of NHEJ efficiency in mouse models, but whether NHEJ and HR change with age in humans and the underlying mechanisms of such a change remain uncharacterized. Here, using 50 eyelid fibroblast cell lines isolated from healthy donors at the age of 16-75 years, we demonstrate that the efficiency and fidelity of NHEJ, and the efficiency of HR decline with age, leading to increased IR sensitivity in cells isolated from old donors. Mechanistic analysis suggests that decreased expression of XRCC4, Lig4 and Lig3 drives the observed, age-associated decline of NHEJ efficiency and fidelity. Restoration of XRCC4 and Lig4 significantly promotes the fidelity and efficiency of NHEJ in aged fibroblasts. In contrast, essential HR-related factors, such as Rad51, do not change in expression level with age, but Rad51 exhibits a slow kinetics of recruitment to DNA damage sites in aged fibroblasts. Further rescue experiments indicate that restoration of XRCC4 and Lig4 may suppress the onset of stress-induced premature cellular senescence, suggesting that improving NHEJ efficiency and fidelity by targeting the NHEJ pathway holds great potential to delay aging and mitigate aging-related pathologies. PMID- 27391798 TI - Expression of Twist2 is controlled by T-cell receptor signaling and determines the survival and death of thymocytes. AB - Self-reactive thymocytes are eliminated by negative selection, whereas competent thymocytes survive by positive selection. The strength of the T-cell receptor (TCR) signal determines the fate of thymocytes undergoing either positive or negative selection. The TCR signal strength is relatively higher in negative selection than in positive selection and induces pro-apoptotic molecules such as Nur77 and Nor-1, which are members of the orphan nuclear receptor family, that then cause TCR-mediated apoptosis. However, at the molecular level, it remains unclear how positive or negative selection is distinguished based on the TCR signal. We found that the expression of Twist2 is differentially regulated in positively and negatively selected thymocytes. In particular, TCR signal strength that elicits positive selection induces Twist2 expression via the Ca2+-Cacineurin NFATc3 pathway, whereas strength of the TCR signal that results in negative selection abolishes NFATc3-dependent Twist2 induction via specific activation of the JNK pathway. Using Twist2-deficient and Twist2 transgenic mice, we also found that Twist2 determines thymocyte sensitivity to TCR-mediated apoptosis by regulating the expression of Nur77 and Nor-1. Twist2 partially retains histone deacetylase 7 (HDAC7) in the nucleus and recruits it to the Nur77 promoter region to repress Nur77 in positively selected thymocytes. Thus our results suggest a molecular mechanism of how thymocytes interpret the strength of the TCR signal and how TCR sensitivity is controlled during thymic selection. PMID- 27391800 TI - Interrelationship between Changes in the Amyloid beta 42/40 Ratio and Presenilin 1 Conformation. AB - The ratio of the longer (i.e., Abeta42/Abeta43) to shorter (i.e. Abeta40) species is a critical factor determining amyloid fibril formation, neurotoxicity and progression of the amyloid pathology in Alzheimer's disease. The relative levels of the different Abeta species are affected by activity and conformation of the gamma-secretase complex catalytic component - presenilin 1 (PS1). The enzyme exists in a dynamic equilibrium of the conformational states, with so-called "close" conformation associated with the shift of the gamma-secretase cleavage towards the production of longer, neurotoxic Abeta species. In the current study, fluorescence lifetime imaging microscopy, spectral Forster resonance energy transfer, calcium imaging and cytotoxicity assays were utilized to explore reciprocal link between the Abeta42 and Abeta40 peptides present at various ratios and PS1 conformation in primary neurons. We report that exposure to Abeta peptides at a relatively high ratio of Abeta42/40 causes conformational change within the PS1 subdomain architecture towards the pathogenic "closed" state. Mechanistically, the Abeta42/40 peptides present at the relatively high ratio increase intracellular calcium levels, which were shown to trigger pathogenic PS1 conformation. This indicates that there is a reciprocal crosstalk between the extracellular Abeta peptides and PS1 conformation within a neuron, with Abeta40 showing some protective effect. The pathogenic shift within the PS1 domain architecture may further shift the production of Abeta peptides towards the longer, neurotoxic Abeta species. These findings link elevated calcium, Abeta42 and PS1/gamma-secretase conformation, and offer possible mechanistic explanation of the impending exacerbation of the amyloid pathology. PMID- 27391799 TI - Astroglial connexin43 contributes to neuronal suffering in a mouse model of Alzheimer's disease. AB - In Alzheimer's disease (AD), astrocyte properties are modified but their involvement in this pathology is only beginning to be appreciated. The expression of connexins, proteins forming gap junction channels and hemichannels, is increased in astrocytes contacting amyloid plaques in brains of AD patients and APP/PS1 mice. The consequences on their channel functions was investigated in a murine model of familial AD, the APPswe/PS1dE9 mice. Whereas gap junctional communication was not affected, we revealed that hemichannels were activated in astrocytes of acute hippocampal slices containing Abeta plaques. Such hemichannel activity was detected in all astrocytes, whatever their distance from amyloid plaques, but with an enhanced activity in the reactive astrocytes contacting amyloid plaques. Connexin43 was the main hemichannel contributor, however, a minor pannexin1 component was also identified in the subpopulation of reactive astrocytes in direct contact with plaques. Distinct regulatory pathways are involved in connexin and pannexin hemichannel activation. Inflammation triggered pannexin hemichannel activity, whereas connexin43 hemichannels were activated by the increase in resting calcium level of astrocytes. Importantly, hemichannel activation led to the release of ATP and glutamate that contributed to maintain a high calcium level in astrocytes placing them in the center of a vicious circle. The astroglial targeted connexin43 gene knocking-out in APPswe/PS1dE9 mice allowed to diminish gliotransmitter release and to alleviate neuronal damages, reducing oxidative stress and neuritic dystrophies in hippocampal neurons associated to plaques. Altogether, these data highlight the importance of astroglial hemichannels in AD and suggest that blocking astroglial hemichannel activity in astrocytes could represent an alternative therapeutic strategy in AD. PMID- 27391801 TI - Expression and knockdown of zebrafish folliculin suggests requirement for embryonic brain morphogenesis. AB - BACKGROUND: Birt-Hogg-Dube syndrome (BHD) is a dominantly inherited familial cancer syndrome characterised by the development of benign skin fibrofolliculomas, multiple lung and kidney cysts, spontaneous pneumothorax and susceptibility to renal cell carcinoma. BHD is caused by mutations in the gene encoding Folliculin (FLCN). Little is known about what FLCN does in a healthy individual and how best to treat those with BHD. As a first approach to developing a vertebrate model for BHD we aimed to identify the temporal and spatial expression of flcn transcripts in the developing zebrafish embryo. To gain insights into the function of flcn in a whole organism system we generated a loss of function model of flcn by the use of morpholino knockdown in zebrafish. RESULTS: flcn is expressed broadly and upregulated in the fin bud, somites, eye and proliferative regions of the brain of the Long-pec stage zebrafish embryos. Together with knockdown phenotypes, expression analysis suggest involvement of flcn in zebrafish embryonic brain development. We have utilised the zFucci system, an in vivo, whole organism cell cycle assay to study the potential role of flcn in brain development. We found that at the 18 somite stage there was a significant drop in cells in the S-M phase of the cell cycle in flcn morpholino injected embryos with a corresponding increase of cells in the G1 phase. This was particularly evident in the brain, retina and somites of the embryo. Timelapse analysis of the head region of flcn morpholino injected and mismatch control embryos shows the temporal dynamics of cell cycle misregulation during development. CONCLUSIONS: In conclusion we show that zebrafish flcn is expressed in a non-uniform manner and is likely required for the maintenance of correct cell cycle regulation during embryonic development. We demonstrate the utilisation of the zFucci system in testing the role of flcn in cell proliferation and suggest a function for flcn in regulating cell proliferation in vertebrate embryonic brain development. PMID- 27391802 TI - Downstream consequences of melanoma screening in a community practice setting: First results. AB - BACKGROUND: Population-based screening for the early detection of melanoma holds great promise for reducing melanoma mortality, but evidence is needed to determine whether benefits outweigh risks. Skin surgeries and dermatology visits after screening were assessed to indicate potential physical, psychological, and financial consequences. METHODS: Targeted primary care providers (PCPs) at the University of Pittsburgh Medical Center were trained to detect early melanoma using the INFORMED (INternet course FOR Melanoma Early Detection) program. The authors analyzed aggregated administrative data describing 3 groups of patients aged >=35 years who had received an annual physical examination by PCPs: group A1 included patients of PCPs from the group with the highest percentage of INFORMED trained providers, group A2 included patients of PCPs from the group with a lower percentage of INFORMED-trained providers, and group B included patients of PCPs without INFORMED training. RESULTS: INFORMED-trained PCPs screened 1572 of 16,472 patients in groups A1 or A2 and none of the 56,261 patients in group B. In group A1, there was a 79% increase (95% confidence interval, 15%-138%) in melanoma diagnoses noted; no increase was observed for the other groups, and no substantial increase in skin surgeries or dermatology visits occurred in any group. CONCLUSIONS: A large-scale melanoma screening using the INFORMED program was conducted in Pennsylvania. To the best of the authors' knowledge, the current study is the first analysis of downstream results and the findings indicate increased melanoma diagnoses but little impact on skin surgeries or dermatology visits. This result provides some reassurance that such efforts can be conducted without major adverse consequences, at least as measured by these parameters, and therefore should be considered for more widespread use. Cancer 2016;122:3152-6. (c) 2016 American Cancer Society. PMID- 27391804 TI - Study on Nanobubble-on-Pancake Objects Forming at Polystyrene/Water Interface. AB - Surface nanobubbles, which are the main gaseous state forming at the solid/liquid interface, have received extensive attention due to their peculiar features and potential applications. Nano/micro pancakes and interfacial gas enrichment (IGE) are observed at the water-solid interface, which suggest nanobubbles may coexist with IGE. An intuitive case for the coexistence of nanobubbles and IGE is the nanobubble-on-pancake-like objects. However, it still is not clear whether nanobubbles sit on top of an IGE or the IGE surrounds a nanobubble, which increasingly is seen to be important for understanding the stability and small contact angle of nanobubbles. In this study, the nanobubble-on-pancake-like objects were investigated on a polystyrene (PS) surface. Considering the nanobubble-like objects forming on PS film might be blisters formed because of osmosis, whether such objects are gaseous state or blisters therefore was investigated first. Then, the structure of the nanobubble-on-pancake-like object was analyzed, on the basis of which the stability of nanobubbles under tip perturbation was discussed. The pancake-like domains of the bubble-on-pancake composite disappeared, but the bubble part remained. This indicates that nanobubbles do not sit on top of the pancakes, but are pinned on the solid surface. This is in good agreement with the contact line pinning theory, and is helpful to understanding the abnormal long lifetime (stability) of nanobubbles. PMID- 27391803 TI - Mammalian tolloid proteinases: role in growth factor signalling. AB - Tolloid proteinases are essential for tissue patterning and extracellular matrix assembly. The members of the family differ in their substrate specificity and activity, despite sharing similar domain organization. The mechanisms underlying substrate specificity and activity are complex, with variation between family members, and depend on both multimerization and substrate interaction. In addition, enhancers, such as Twisted gastrulation (Tsg), promote cleavage of tolloid substrate, chordin, to regulate growth factor signalling. Although Tsg and mammalian tolloid (mTLD) are involved in chordin cleavage, no interaction has been detected between them, suggesting Tsg induces a change in chordin to increase susceptibility to cleavage. All members of the tolloid family bind the N terminus of latent TGFbeta-binding protein-1, providing support for their role in TGFbeta signalling. PMID- 27391806 TI - Human chorionic gonadotropin detection in cerebrospinal fluid of patients with a germinoma and its prognostic significance: assessment by using a highly sensitive enzyme immunoassay. AB - OBJECTIVE Human chorionic gonadotropin (HCG) can be detected in a certain population of patients with a germinoma, but the frequency of germinoma HCG secretion and the prognostic value of HCG in the CSF are unknown. METHODS The authors measured HCG levels in sera and CSF in patients with a histologically confirmed germinoma by using a highly sensitive assay known as an immune complex transfer enzyme immunoassay (EIA), which is more than 100 times as sensitive as the conventional method, and they analyzed the correlation between HCG levels and the prognoses of patients with a germinoma. RESULTS HCG levels in sera and CSF of 35 patients with a germinoma were examined with the immune complex transfer EIA. The median CSF HCG levels in patients with a germinoma during the pretreatment and posttreatment evaluations were 192.5 pg/ml (range 1.2-13,116.5 pg/ml) and 18.7 pg/ml (1.2-283.9 pg/ml), respectively. Before treatment, the CSF HCG level was greater than the cutoff value in 85.7% of the patients with a germinoma. The authors compared survival rates among the patients by using a CSF HCG cutoff level of 1000 pg/ml, and the difference was statistically significant between the groups (p = 0.029, log-rank test). CONCLUSIONS Results of this study demonstrate that most germinomas secrete HCG. Patients with a germinoma that secretes higher amounts of HCG in their CSF experienced recurrence more frequently than those with lower CSF HCG levels. PMID- 27391805 TI - Disentangling the External Reference Frames Relevant to Tactile Localization. AB - Different reference frames appear to be relevant for tactile spatial coding. When participants give temporal order judgments (TOJ) of two tactile stimuli, one on each hand, performance declines when the hands are crossed. This effect is attributed to a conflict between anatomical and external location codes: hand crossing places the anatomically right hand into the left side of external space. However, hand crossing alone does not specify the anchor of the external reference frame, such as gaze, trunk, or the stimulated limb. Experiments that used explicit localization responses, such as pointing to tactile stimuli rather than crossing manipulations, have consistently implicated gaze-centered coding for touch. To test whether crossing effects can be explained by gaze-centered coding alone, participants made TOJ while the position of the hands was manipulated relative to gaze and trunk. The two hands either lay on different sides of space relative to gaze or trunk, or they both lay on one side of the respective space. In the latter posture, one hand was on its "regular side of space" despite hand crossing, thus reducing overall conflict between anatomical and external codes. TOJ crossing effects were significantly reduced when the hands were both located on the same side of space relative to gaze, indicating gaze-centered coding. Evidence for trunk-centered coding was tentative, with an effect in reaction time but not in accuracy. These results link paradigms that use explicit localization and TOJ, and corroborate the relevance of gaze-related coding for touch. Yet, gaze and trunk-centered coding did not account for the total size of crossing effects, suggesting that tactile localization relies on additional, possibly limb-centered, reference frames. Thus, tactile location appears to be estimated by integrating multiple anatomical and external reference frames. PMID- 27391807 TI - Correction: An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy. AB - [This corrects the article DOI: 10.1371/journal.pone.0155406.]. PMID- 27391808 TI - Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment. AB - Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a 'more clinically relevant' tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in alpha-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation. PMID- 27391809 TI - Interplay between stress response genes associated with attention-deficit hyperactivity disorder and brain volume. AB - The glucocorticoid receptor plays a pivotal role in the brain's response to stress; a haplotype of functional polymorphisms in the NR3C1 gene encoding this receptor has been associated with attention-deficit hyperactivity disorder (ADHD). The serotonin transporter (5-HTT) gene polymorphism 5-HTTLPR is known to influence the relation between stress exposure and ADHD severity, which may be partly because of its reported effects on glucocorticoid levels. We therefore investigated if NR3C1 moderates the relation of stress exposure with ADHD severity and brain structure, and the potential role of 5-HTTLPR. Neuroimaging, genetic and stress exposure questionnaire data were available for 539 adolescents and young adults participating in the multicenter ADHD cohort study NeuroIMAGE (average age: 17.2 years). We estimated the effects of genetic variation in NR3C1 and 5-HTT, stress exposure and their interactions on ADHD symptom count and gray matter volume. We found that individuals carrying the ADHD risk haplotype of NR3C1 showed significantly more positive relation between stress exposure and ADHD severity than non-carriers. This gene-environment interaction was significantly stronger for 5-HTTLPR L-allele homozygotes than for S-allele carriers. These two- and three-way interactions were reflected in the gray matter volume of the cerebellum, parahippocampal gyrus, intracalcarine cortex and angular gyrus. Our findings illustrate how genetic variation in the stress response pathway may influence the effects of stress exposure on ADHD severity and brain structure. The reported interplay between NR3C1 and 5-HTT may further explain some of the heterogeneity between studies regarding the role of these genes and hypothalamic-pituitary-adrenal axis activity in ADHD. PMID- 27391810 TI - Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage. AB - Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v) sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC) was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 MUm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods. PMID- 27391811 TI - Prevalence of elevated serum anti-N-methyl-D-aspartate receptor antibody titers in patients presenting exclusively with psychiatric symptoms: a comparative follow-up study. AB - BACKGROUND: Increasing numbers of patients with elevated anti-N-methyl-D aspartate (NMDA) receptor antibody titers presenting exclusively with psychiatric symptoms have been reported. The aim of the present study was to clarify the prevalence of elevated serum anti-NMDA receptor antibody titers in patients with new-onset or acute exacerbations of psychiatric symptoms. In addition, the present study aimed to investigate the association between elevated anti-NMDA receptor titers and psychiatric symptoms. METHODS: The present collaborative study included 59 inpatients (23 male, 36 female) presenting with new-onset or exacerbations of schizophrenia-like symptoms at involved institutions from June 2012 to March 2014. Patient information was collected using questionnaires. Anti NMDA receptor antibody titers were measured using NMDAR NR1 and NR2B co transfected human embryonic kidney (HEK) 293 cells as an antigen (cell-based assay). Statistical analyses were performed for each questionnaire item. RESULTS: The mean age of participants was 42.0 +/- 13.7 years. Six cases had elevated serum anti-NMDA antibody titers (10.2 %), four cases were first onset, and two cases with disease duration >10 years presented with third and fifth recurrences. No statistically significant difference in vital signs or major symptoms was observed between antibody-positive and antibody-negative groups. However, a trend toward an increased frequency of schizophrenia-like symptoms was observed in the antibody-positive group. CONCLUSION: Serum anti-NMDA receptor antibody titers may be associated with psychiatric conditions. However, an association with specific psychiatric symptoms was not observed in the present study. Further studies are required to validate the utility of serum anti-NMDA receptor antibody titer measurements at the time of symptom onset. PMID- 27391812 TI - Glycoside Hydrolase (GH) 45 and 5 Candidate Cellulases in Aphelenchoides besseyi Isolated from Bird's-Nest Fern. AB - Five Aphelenchoides besseyi isolates collected from bird's-nest ferns or rice possess different parasitic capacities in bird's-nest fern. Two different glycoside hydrolase (GH) 45 genes were identified in the fern isolates, and only one was found in the rice isolates. A Abe GH5-1 gene containing an SCP-like family domain was found only in the fern isolates. Abe GH5-1 gene has five introns suggesting a eukaryotic origin. A maximum likelihood phylogeny revealed that Abe GH5-1 is part of the nematode monophyletic group that can be clearly distinguished from those of other eukaryotic and bacterial GH5 sequences with high bootstrap support values. The fern A. besseyi isolates were the first parasitic plant nematode found to possess both GH5 and GH45 genes. Surveying the genome of the five A. besseyi isolates by Southern blotting using an 834 bp probe targeting the GH5 domain suggests the presence of at least two copies in the fern origin isolates but none in the rice-origin isolates. The in situ hybridization shows that the Abe GH5-1 gene is expressed in the nematode ovary and testis. Our study provides insights into the diversity of GH in isolates of plant parasitic nematodes of different host origins. PMID- 27391813 TI - Hydrophobic Properties of Biofilm-Enriched Hybrid Mortar. AB - A mortar hybrid material is presented in which biomineralization processes are stimulated by adding a biological component, i.e., bacterial biofilm, to standard mortar. A material is obtained that exhibits increased roughness on the microscale and the nanoscale. Accordingly, the hybrid mortar not only resists wetting but also suppresses the uptake of water by capillary forces. PMID- 27391814 TI - Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119. AB - G protein-coupled receptor (GPR) 119 is expressed in pancreatic beta-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID- 27391815 TI - Recurrent pseudohypopyon in association with primary vitreoretinal lymphoma: a case report. AB - BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is a rare and fatal ocular malignancy that is mostly classified as diffuse large B cell lymphoma (DLBCL). PVRL is often fatal because of its association with the central nervous system (CNS). PVRL frequently masquerades as uveitis and sometimes recurs in clinical findings as keratic precipitates (KPs) and subretinal lesions. Pseudohypopyon is one of the clinical findings of the local recurrence of PVRL and is treated with radiotherapy; however, the effectiveness of local control with an intravitreal injection of methotrexate (MTX) has not yet been determined. We herein present a case of recurrent vitreoretinal lymphoma that repeatedly developed pseudohypopyon and treated with intravitreal MTX. CASE PRESENTATION: A 64-year-old woman was diagnosed with PVRL involving primary central nervous system lymphoma (PCNSL). She received radiotherapy to the whole brain and a local ocular treatment, which resulted in temporary remission of the disease. Pseudohypopyon was detected during the follow-up. It was 2-mm high, viscous, and swollen in the center. Anterior chamber biopsy revealed the presence of atypical lymphocytes, indicating the recurrence of DLBCL. Pseudohypopyon was treated with intravitreal methotrexate and completely disappeared. Pseudohypopyon has since repeatedly appeared and been treated with intravitreal MTX each time. The recurrence of PVRL with KPs and subretinal invasion was treated with intravitreal MTX each time. Recurrence with pseudohypopyon was not simultaneous with KPs or subretinal invasion. No CNS involvement was detected during the observation period. CONCLUSIONS: Pseudohypopyon is one of the signs of recurrent vitreoretinal lymphoma. Although pseudohypopyon was temporarily controlled with intravitreal MTX, this treatment did not completely induce its remission. PMID- 27391816 TI - Market Confidence Predicts Stock Price: Beyond Supply and Demand. AB - Stock price prediction is an important and challenging problem in stock market analysis. Existing prediction methods either exploit autocorrelation of stock price and its correlation with the supply and demand of stock, or explore predictive indictors exogenous to stock market. In this paper, using transaction record of stocks with identifier of traders, we introduce an index to characterize market confidence, i.e., the ratio of the number of traders who is active in two successive trading days to the number of active traders in a certain trading day. Strong Granger causality is found between the index of market confidence and stock price. We further predict stock price by incorporating the index of market confidence into a neural network based on time series of stock price. Experimental results on 50 stocks in two Chinese Stock Exchanges demonstrate that the accuracy of stock price prediction is significantly improved by the inclusion of the market confidence index. This study sheds light on using cross-day trading behavior to characterize market confidence and to predict stock price. PMID- 27391817 TI - Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity. AB - BACKGROUND: Network analysis is a powerful way of modeling chromatin interactions. Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts. RESULTS: We use high resolution promoter capture Hi-C and Hi-Cap data as well as ChIA-PET data from mouse embryonic stem cells to investigate promoter-centered chromatin interaction networks and calculate the presence of specific epigenomic features in the chromatin fragments constituting the nodes of the network. We estimate the association of these features with the topology of four chromatin interaction networks and identify features localized in connected areas of the network. Polycomb group proteins and associated histone marks are the features with the highest chromatin assortativity in promoter-centered networks. We then ask which features distinguish contacts amongst promoters from contacts between promoters and other genomic elements. We observe higher chromatin assortativity of the actively elongating form of RNA polymerase 2 (RNAPII) compared with inactive forms only in interactions between promoters and other elements. CONCLUSIONS: Contacts among promoters and between promoters and other elements have different characteristic epigenomic features. We identify a possible role for the elongating form of RNAPII in mediating interactions among promoters, enhancers, and transcribed gene bodies. Our approach facilitates the study of multiple genome-wide epigenomic profiles, considering network topology and allowing the comparison of chromatin interaction networks. PMID- 27391818 TI - Management of hypertension and multiple risk factors to enhance cardiovascular health - a feasibility study in Singapore polyclinics. AB - BACKGROUND: High blood pressure (BP) is a leading contributor to cardiovascular mortality globally. There is scarcity of information on effective health systems interventions to lower BP and reduce cardiovascular risk in Southeast Asian countries. We conducted a pilot exploratory trial on 100 adults aged 40 years or older with uncontrolled hypertension to optimize the design for a structured multi-component intervention in primary care clinics for management of hypertension. METHODS: Two clinics were involved, each enrolling 50 participants, with one as the intervention clinic and the other as the control (usual care). The intervention comprised the following four components: 1) an algorithm-driven intervention using a fixed-dose combination (FDC) antihypertensive treatment and lipid lowering medication for high risk individuals, 2) subsidized FDC antihypertensive medication; 3) motivational conversation (MC) for high risk individuals; and 4) telephone follow-ups of all individuals. The process outcomes were intervention fidelity measures. The outcomes of change in parameters of interest were healthy lifestyle index (composite score of body mass index, physical activity, dietary habit, dietary quality and smoking), adherence to antihypertensive medications, and systolic and diastolic BP from baseline to follow-up at 3 months. RESULTS: Greater than 90 % fidelity was achieved for 3 of the 4 intervention components. Although not designed for conclusive results, the healthy lifestyle score increased by 0.16 (+/-0.68) with the intervention and decreased by 0.18 (+/-0.75) with usual care (p = 0.02). Adherence to anti hypertensive medications at follow-up was 95.3 % in the intervention group compared to 83.8 % for usual care (p = 0.01). Systolic and diastolic BP decreased in both intervention and control groups, although statistical significance between groups was not achieved. Hypertensive individuals rated all intervention components 'highly favorable' on a Likert scale. CONCLUSIONS: Our findings indicate that the proposed, structured multi-component approach for management of hypertension is feasible for implementation in primary care clinics in Singapore, with some changes to the protocol. The observed improvement in the healthy lifestyle index and adherence to anti-hypertensive medications is promising. A large scale, adequately powered trial would be informative to assess intervention effectiveness on BP and cardiovascular risk reduction. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov. ClinicalTrials.gov number NCT02330224 . Registered on 28 December 2014. PMID- 27391819 TI - Clinical Characteristics of Young Type 2 Diabetes Patients with Atherosclerosis. AB - OBJECTIVE: The prevalence of type 2 diabetes is increasing rapidly in the young population. The clinical characteristics and risk factors for young type 2 diabetes patients with atherosclerosis are not fully explicated. The aim of the present study was to investigate various clinical and biochemical characteristics of young type 2 diabetic patients with atherosclerosis. DESIGN AND METHODS: This was a cross-sectional study. The study involved 2199 hospitalized patients with type 2 diabetes. The young patients were classified into the atherosclerotic group or the non-atherosclerotic group, and we also enrolled an older group with peripheral atherosclerosis disease and an age of at least 45 years. Comparisons were made between the different groups to investigate the cardiovascular and metabolic risk profiles of young type 2 diabetes patients with atherosclerosis. We also used logistic regression models to assess the atherosclerosis risk factors for young patients. RESULTS: Compared to older type 2 diabetes patients with atherosclerosis, young patients with atherosclerosis had more deleterious profiles of weight and hyperlipidemia. Only age and diabetes duration were found to be significant independent risk factors for atherosclerosis in young patients. The ratio of the presence of atherosclerosis in the lower extremity arteries alone was significantly higher in young patients than older patients (26.4% vs. 14.0%, P = 0.000). CONCLUSION: Young type 2 diabetes patients with atherosclerosis have more adverse cardiovascular risk profiles and inadequate control of these risk factors. Lower extremity examination is of high importance in young patients. PMID- 27391820 TI - Reply: Cosmetic Body Lift. PMID- 27391822 TI - Cosmetic Body Lift. PMID- 27391823 TI - Body Contouring. PMID- 27391824 TI - Simplifying Blepharoplasty. PMID- 27391825 TI - The Effect of Abdominoplasty and Outcome of Rectus Fascia Plication on Health Related Quality of Life in Post-Bariatric Surgery Patients. PMID- 27391826 TI - Lipofilling of the Breast Does Not Increase the Risk of Recurrence of Breast Cancer: A Matched Controlled Study. PMID- 27391827 TI - Does the Eyebrow Sag with Aging? An Anthropometric Study of 95 Caucasians from 20 to 79 Years of Age. PMID- 27391830 TI - Remote Ischemic Conditioning Improves Blood Flow and Oxygen Saturation in Pedicled and Free Surgical Flaps. AB - BACKGROUND: Surgical flaps have become safe and reliable reconstructive tools, but total flap loss rates as high as 25 percent and partial flap loss rates as high as 36 percent have been reported due to insufficient perfusion. Therefore, a reliable, noninvasive, and effective way to improve the microcirculation of surgical flaps is desirable. The aim of this study was to assess the effect of remote ischemic conditioning on the microcirculation of pedicled and free surgical flaps. METHODS: Thirty patients undergoing free (n = 20) and pedicled (n = 10) tissue transfer were included in this study. Remote ischemic conditioning was applied on the upper extremity for three cycles on postoperative days 1, 5, and 12. Blood flow, tissue oxygen saturation, and relative hemoglobin content were measured by means of a combination of laser Doppler and spectroscopy (O2C device) in the flap and the surrounding tissue. The relative increase compared with baseline measurements was assessed. RESULTS: Blood flow increased significantly in controls on all 3 postoperative days (p < 0.05 for all). In free flaps, tissue oxygen saturation improved significantly on postoperative days 1 and 12 and blood flow improved significantly on postoperative days 5 and 12 (p < 0.05). In pedicled flaps, blood flow and tissue oxygen saturation increased on postoperative day12, but not significantly. CONCLUSIONS: Remote ischemic conditioning is a safe, inexpensive, fast, and reliable method to improve the microcirculation of surgical flaps. Further research is warranted to see whether such an improvement translates into improved flap survival, but it is likely. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27391831 TI - Impact of Fronto-Orbital Advancement on Frontal Sinus Volume, Morphology, and Disease in Nonsyndromic Craniosynostosis. AB - BACKGROUND: Fronto-orbital advancement for nonsyndromic craniosynostosis has been thought to injure frontal sinus buds, lead to chronic sinus disease, and influence final forehead shape. This study investigates the effect of fronto orbital advancement in infancy on subsequent frontal sinus volume, morphology, and disease. METHODS: The authors conducted a retrospective review of nonsyndromic craniosynostosis patients treated with fronto-orbital advancement in infancy with a head computed tomographic scan obtained at age 7 to 18 years. Facial trauma patients served as age-matched controls. Frontal sinus characteristics were determined using three-dimensional reconstructions. RESULTS: The study included 33 nonsyndromic craniosynostosis patients who underwent fronto orbital advancement (n = 20 unicoronal; n = 13 metopic) and 20 control patients. The incidence of at least unilateral pneumatization was 94 percent for fronto orbital advancement subjects and 95 percent for control subjects. Mean frontal sinus volumes for unicoronal synostosis, metopic synostosis, and control groups were 3427 +/- 2294, 4576 +/- 3510, and 4157 +/- 3963 mm, respectively (p = 0.598). Asymmetry scores were as follows: unicoronal synostosis, 56 +/- 35 percent; metopic synostosis, 36 +/- 33 percent; and control, 23 +/- 24 percent (p = 0.010). Unicoronal subjects displayed prominent asymmetry, with increased pneumatization on the unaffected side. Frontal sinus volume correlated with age at computed tomography but not with age at fronto-orbital advancement. Interrater reliability was 0.997. One fronto-orbital advancement subject and zero control subjects demonstrated computed tomographic evidence of frontal sinus disease. CONCLUSIONS: Frontal sinus volume, morphology, and disease do not differ significantly between control subjects and nonsyndromic craniosynostosis subjects following fronto-orbital advancement, but subtle differences such as increased asymmetry in the unicoronal synostosis group can be appreciated. Further research with syndromic craniosynostosis patients undergoing multiple procedures may help elucidate the association between surgical disruption and frontal sinus development. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27391832 TI - Effect of Botulinum Toxin Type A on TGF-beta/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation. AB - BACKGROUND: One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF) beta1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-beta1 signaling, in human fibroblasts. METHODS: In vitro, cultured human fibroblasts were treated with TGF-beta1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry. RESULTS: In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. CONCLUSION: This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-beta/Smad signaling pathway. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 27391833 TI - Autologous Fat Grafting for Pedal Fat Pad Atrophy: A Prospective Randomized Clinical Trial. AB - BACKGROUND: Pedal fat pad atrophy is associated with pain, decreased tissue thickness, and increased foot pressures. To date, no objective studies investigating the use of fat grafting to the forefoot have been performed. The authors hypothesize that pedal fat grafting can reduce pain, increase tissue thickness, and decrease pedal pressures. METHODS: A prospective randomized study was performed to assess tissue thickness, pain, and foot pressures. Group 1 underwent fat grafting immediately with 1-year follow-up, and group 2 underwent conservative management for 1 year. RESULTS: Thirteen patients (two men and 11 women) constituted group 1 and 12 patients (four men and eight women) constituted group 2. Ten patients in group 1 underwent bilateral injections with a mean volume of 4.8 cc per foot. Mean follow-up time was 11.1 +/- 5.4 months for group 1 and 13.8 +/- 4.2 months for group 2. At 1 year, group 1 demonstrated improved foot function (p = 0.022), pain (p = 0.022), and work/leisure activities (p = 0.021). Group 1 had no change in tissue thickness, whereas in group 2, the right third metatarsal tissue thickness decreased significantly (p = 0.036). Foot pressures in group 1 did not improve; however, group 2 had a significant increase in left foot pressure (p = 0.011). When comparing the groups at 1 year, group 2 had significantly higher foot pressures and forces than group 1 (p < 0.05). CONCLUSIONS: Pedal fat grafting significantly improves pain and disability outcomes, and prevents against worsening foot pressures. Future analysis will reveal whether fat grafting has lasting efficacy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. PMID- 27391834 TI - The Profunda Artery Perforator Flap Experience for Breast Reconstruction. AB - BACKGROUND: The profunda artery perforator flap was first introduced for breast reconstruction in 2010. In this article, the authors analyze the results of all profunda artery perforator flaps performed by their group to date. METHODS: A retrospective review was completed of consecutive profunda artery perforator flaps performed by the senior author (R.J.A.) from 2010 to 2014. Patient demographics, indications, operative techniques, flap specifics, complications, and number of operations were recorded. RESULTS: Ninety-six patients have undergone 164 profunda artery perforator flap operations for breast reconstruction since 2010. Reconstructions were performed following breast cancer management (59.5 percent), following prophylactic mastectomy for cancer risk reduction (35.7 percent), and for congenital breast deformity (4.8 percent). The average age of the patients was 48 years (range, 24 to 64 years) and their average body mass index was 22.5 kg/m. Average flap weight was 367.4 g and average pedicle length was found to be 10.2 cm. The success rate of the profunda artery perforator flap was greater than 99 percent, with a 3 percent take-back rate and only one flap loss recorded. Complications included hematoma (1.9 percent), seroma (6 percent), fat necrosis (7 percent), and donor-site infection (1.9 percent). CONCLUSIONS: The profunda artery perforator flap is an excellent option for breast reconstruction. Advantages include a reliable blood supply, long pedicle, thick donor tissue, and a favorable donor site. Currently, the profunda artery perforator flap is second only to the deep inferior epigastric artery perforator among flaps used by the authors for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27391835 TI - Autologous, Allogeneic, and Synthetic Augmentation Grafts in Nipple Reconstruction. PMID- 27391836 TI - Understanding and Overcoming Implicit Gender Bias in Plastic Surgery. AB - BACKGROUND: Although explicit sex-based discrimination has largely been deemed unacceptable in professional settings, implicit gender bias persists and results in a significant lack of parity in plastic surgery and beyond. Implicit gender bias is the result of a complex interplay of cultural and societal expectations, learned behaviors, and standardized associations. As such, both male and female surgeons are subject to its influence. METHODS: A review of the literature was conducted, examining theories of gender bias, current manifestations of gender bias in plastic surgery and other fields, and interventions designed to address gender bias. RESULTS: Multiple studies demonstrate persistent gender bias that impacts female physicians at all levels of training. Several institutions have enacted successful interventions to identify and address gender bias. CONCLUSIONS: Explicit gender bias has largely disappeared, yet unconscious or implicit gender bias persists. A wide-scale commitment to addressing implicit gender bias in plastic surgery is necessary and overdue. Recommendations include immediate actions that can be undertaken on an individual basis, and changes that should be implemented at a national and international level by leaders in the field. PMID- 27391837 TI - Vascular Perfusion of the Facial Skin: Implications in Allotransplantation of Facial Aesthetic Subunits. AB - BACKGROUND: As the field of face transplantation develops, it may be possible to transplant segments of facial skin to replace facial aesthetic subunits in selected cases. The aim of this study was to identify the more reliable vascular pedicles of each facial aesthetic subunit for its use in transplantation METHODS:: Six full facial soft-tissue flaps were harvested, and the external carotid artery was identified and cannulated proximal to the facial artery. Next, radiopaque contrast was injected through the facial artery into three of the facial flaps and through the superficial temporal artery in the other three facial flaps. After vascular injections, three-dimensional computed tomographic arteriographs of the faces were obtained, allowing analysis of the arterial anatomy and perfusion in different facial aesthetic subunits. RESULTS: The chin, lower lip, upper lip, medial cheek, nose, and periorbital units were perfused in all facial flaps where the facial artery was injected and in none of those where the superficial temporal artery was injected. The lateral cheek was perfused in 100 percent of the superficial temporal artery flaps and in 67 percent of the facial artery flaps. The lateral forehead contained contrast in 100 percent of the superficial temporal artery-injected flaps and in none of the facial artery injected flaps, and the medial foreheads contained contrast in 67 percent of the facial artery-injected flaps and in 67 percent of the superficial temporal artery injected flaps. CONCLUSION: The majority of the facial subunits can be harvested based on the facial artery pedicle, with the exception of the lateral forehead, which is based on the superficial temporal artery. PMID- 27391838 TI - Reinterpretation of Electrodiagnostic Studies and Magnetic Resonance Imaging Scans in Patients with Nontraumatic "Isolated" Anterior Interosseous Nerve Palsy. AB - BACKGROUND: Different hypotheses have been proposed for the pathophysiology of anterior interosseous nerve palsy: compression, fascicular constriction, or nerve inflammation (Parsonage-Turner syndrome). The authors hypothesized that critical reinterpretation of electrodiagnostic studies and magnetic resonance imaging scans of patients with a diagnosis of anterior interosseous nerve palsy could provide insight into the pathophysiology and treatment. METHODS: A retrospective review was performed of all patients with a diagnosis of nontraumatic anterior interosseous nerve palsy and an upper extremity magnetic resonance imaging scan. The original electrodiagnostic study and magnetic resonance imaging scan reports were reinterpreted by a neuromuscular neurologist and musculoskeletal radiologist, respectively, both blinded to the authors' hypothesis. RESULTS: Sixteen patients met the inclusion criteria as having "isolated" anterior interosseous nerve palsy. Physical examination revealed weakness in muscles not innervated by the anterior interosseous nerve in five cases (31 percent), and electrodiagnostic studies showed abnormalities not related to the anterior interosseous nerve in nine of 15 cases (60 percent). In all cases, reinterpretation of the magnetic resonance imaging scans demonstrated atrophy in at least one muscle not innervated by the anterior interosseous nerve and did not reveal any evidence of compression of the anterior interosseous nerve. CONCLUSIONS: All patients in the authors' series with presumed isolated anterior interosseous nerve palsy had magnetic resonance imaging evidence of a more diffuse muscle involvement pattern, without any radiologic signs of nerve compression of the anterior interosseous nerve branch itself. These data strongly support an inflammatory pathophysiology. PMID- 27391839 TI - Adipose-Derived Stem Cell Modulation of T-Cell Regulation Correlates with Heme Oxgenase-1 Pathway Changes. AB - BACKGROUND: The authors' previous proteome study revealed that haptoglobin was involved in adipose-derived stem cell modulation of allotransplant survival and T cell regulation to induce immune tolerance. This study investigated whether adipose-derived stem cells could modulate T-cell regulation through haptoglobin and the downstream heme oxgenase-1 pathway in vitro. METHODS: Splenocytes were isolated from Lewis rat spleens and then CD3 T cells were purified using anti-CD3 beads. Adipose-derived stem cells were harvested from Lewis rats and co-cultured with the T cells. After Transwell co-culture at different periods, the authors analyzed cell proliferation with a bromodeoxyuridine assay. Cell extractions and culture supernatants were collected for further analysis. Heme oxgenase-1 and related protein expression levels from the adipose-derived stem cells and T cells were detected using Western blotting. The related cytokine expression levels were analyzed with enzyme-linked immunosorbent assay kits. Flow cytometry was used to detect the regulatory T-cell proportion. RESULTS: The adipose-derived stem cells significantly suppressed T-cell proliferation. The regulatory T-cell percentages were significantly increased in the adipose-derived stem cells that were co cultured with T cells compared with T cells alone without adipose-derived stem cell co-culture. Heme oxgenase-1 expression in concanavalin A-stimulated T cells that were co-cultured with adipose-derived stem cells revealed a significant increase compared with concanavalin A-stimulated T cells alone. Cytokine assays of the culture supernatants revealed that transforming growth factor-beta and interleukin-10 were significantly increased and interferon-gamma was statistically decreased in the adipose-derived stem cell-co-cultured T-cell group compared with other groups; however, blockade with a heme oxgenase-1 inhibitor (zinc protoporphyrin IX) protected against these changes. CONCLUSION: Adipose derived stem cells modulate T-cell proliferation and enhance regulatory T-cell expression, and this correlated with heme oxgenase-1 expression and related cytokine pathway changes. PMID- 27391840 TI - Direct Synthesis of Water-Soluble Aptamer-Ag2 S Quantum Dots at Ambient Temperature for Specific Imaging and Photothermal Therapy of Cancer. AB - Water-soluble Ag2 S near-infrared (NIR) fluorescent quantum dots (QDs) are directly synthesized at ambient temperature for specific cancer imaging and photothermal therapy (PTT) using a designed aptamer (Apt43) as template, which consists of the following two fragments: an aptamer S2.2 sequence for specifically recognizing the cancer cells and an 18-cytosine (18-C) extending spacer for growing Ag2 S QDs. The synthesized Ag2 S QDs (Apt43-Ag2 S QDs), which exhibit strong absorption and fluorescence emission in the NIR region and high photothermal conversion capabilities, can specifically recognize MCF-7 cells (human breast cancer cells) and are usable as a highly intensified imaging agent for cancer diagnosis. Moreover, they can be applied as photothermal agents for the in vitro killing of MCF-7 cells and the in vivo ablation of tumors, which were constructed on the bodies of nude mice. MCF-7 cells almost quantitatively die after they are incubated with the QDs (at 100 MUg mL(-1) ) for 2 h and irradiated under an 808 nm laser at a power density of 1.0 W cm(-2) for 10 min. The tumors on the nude mice can also be effectively ablated without regrowth during the period of observation (at least 20 d) after PTT. PMID- 27391842 TI - Expression of amphiregulin predicts poor outcome in patients with pancreatic ductal adenocarcinoma. AB - BACKGROUND: The validation of novel diagnostic, prognostic and predictive biomarkers in cancer is crucial for optimizing the choice and efficacy of personalized therapies. The aim of this study was to determine the epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRvIII) and amphiregulin (AREG) protein expression levels and to evaluate the prognostic significance of EGFR, EGFRvIII and AREG in pancreatic ductal adenocarcinoma (PDAC). METHODS: The EGFR, EGFRvIII and AREG protein levels in PDAC (n = 92) were examined by using immunohistochemistry. The associations between EGFRvIII expression, AREG expression, AREG/EGFR co-expression and clinicopathological factors were assessed, the correlation between AREG and EGFR expression was analyzed and the survival analyses were performed. RESULTS: Among the lesions of PDAC, 12 (13 %) stained positive for EGFRvIII, 49 (53.3 %) stained positive for AREG and 22(23.9 %) stained double positive for AREG/EGFR. The relationships between each protein expression level and the clinicopathologic factors were examined, only AREG/EGFR co-expression was significantly related to tumor differentiation (P = 0.032). The correlation between AREG and EGFR expression was statistically insignificant (P = 0.709). Univariate survival analysis proved that high tumor-node-metastasis (TNM) stage, poor tumor differentiation and AREG expression were significant poor prognostic factors for disease-free survival (DFS) and overall survival (OS). By multivariate survival analysis, tumor differentiation was an independent poor prognostic factor for DFS (HR = 1.785, P < 0.05), whereas high TNM stage (HR = 2.25, P < 0.05), poor tumor differentiation (HR = 2.125, P < 0.01), positive resection margins (HR = 1.84, P < 0.05), and AREG expression (HR = 1.822, P < 0.05) were all independent poor prognostic factors for OS. CONCLUSIONS: In conclusion, our data indicate that AREG expression is an important prognostic biomarker in PDAC . PMID- 27391843 TI - Tobacco and cognitive performance in schizophrenia patients: the design of the COGNICO study. AB - People with schizophrenia constitute a substantial part of the people who still smoke. Regarding cognitive performance, the self-medication hypothesis states that patients smoke to improve their cognitive deficits based on the stimulating effects of nicotine. The aim of this paper is to describe in detail the methodology used in the COGNICO study. A quasi-experimental, observational, prospective, multicenter study with follow-ups over 18 months was conducted in three cities in northern Spain (Oviedo, Ourense and Santiago de Compostela). A total of 81 outpatient smokers with schizophrenia were recruited with a mean age 43.35 years (SD = 8.83), 72.8% of them male. They were assigned to 3 groups: a) control group (smokers); b) patients who quit smoking using nicotine patches; c) patients who quit smoking with Varenicline. The MATRICS neuropsychological battery was applied as a primary measure. In addition, a comprehensive assessment of patients was performed, including the number of cigarettes per day, physical and psychological dependence on nicotine and CO expired. Clinical evaluation (PANSS, HDRS, CGI, C-SSRS), anthropometric measurements and vital signs assessment was also performed. The aim is to identify the relationship between the pattern of tobacco use and cognitive performance by comparing scores on the neuropsychological battery MATRICS during the follow-up periods (3, 6, 12 and 18months). The importance of this study lies in addressing a topical issue often ignored by clinicians: the unacceptably high rates of tobacco use in patients with severe mental disorders. PMID- 27391841 TI - Effects of Xiaoshuan enteric-coated capsule on neurovascular functions assessed by quantitative multiparametric MRI in a rat model of permanent cerebral ischemia. AB - BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke. METHODS: Ischemic stroke was induced by permanent middle cerebral artery occlusion (pMCAO). XSECC (420 mg/kg) was orally administered 2 h after stroke and daily thereafter. T2-weighted imaging (T2WI), T2 relaxometry mapping and diffusion tensor imaging (DTI) were used to measure cerebral infarct volume, edema and white matter fiber integrity, respectively. Neurochemical metabolite levels were monitored by (1)H-magnetic resonance spectroscopy ((1)H MRS). Arterial spin labeling (ASL) - cerebral blood flow (CBF) measurements and structural magnetic resonance angiography (MRA) images provided real-time and dynamic information about vascular hemodynamic dysfunction on the 3rd, 7th and 14th days after pMCAO. At the last imaging time point, immunohistochemistry, immunofluorescence as well as transmission electron microscopy (TEM) were used to test the microscopic and ultrastructural changes of NVU. RESULTS: T2WI, T2 relaxometry mapping and Fractional anisotropy (FA) in DTI showed that XSECC significantly reduced cerebral infarct volume, relieved edema and alleviated nerve fiber injuries, respectively. (1)H-MRS provided information about improvement of neuronal/glial metabolism after XSECC treatment. Moreover, ASL - CBF measurements combined with MRA showed that XSECC significantly increased CBF and vascular signal strength and alleviated ischemia-induced morphological changes of arteries in ischemic hemisphere within 14 days after stroke. In addition, neuron specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), CD34 staining and TEM detection indicated that XSECC not only ameliorated neuronal injury, but also reduced endothelial damage and inhibited astrocyte proliferation. CONCLUSIONS: Our results suggested that XSECC has multi-target neurovascular protective effects on ischemic stroke, which may be closely correlated with the improvement of cerebral blood supply and neuronal/glial metabolism. PMID- 27391844 TI - Impulsivity in men with prescription of benzodiazepines and methadone in prison. AB - Benzodiazepines and methadone use has been associated with various neuropsychological impairments. However, to the best of our knowledge, no studies have been carried out on the effect of these substances (either separately or combined) on impulsive personality, including studies in prisoners. The aim of this study is to examine the impulsive personality of a sample of 134 male prisoners using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001) and the UPPS-P Scale (Cyders et al., 2007). Some of these were methadone users, methadone and benzodiazepines users, polydrug users in abstinence and non-dependent drug users. The results showed that drug users have greater sensitivity to reward, positive urgency, negative urgency and sensation seeking than non-dependent users. Methadone users showed more sensitivity to punishment and lack of perseverance with respect to other users. No differences were found between methadone+benzodiazepines users and other groups. The secondary aim is to examine which impulsive personality dimensions are related to the two motivational systems proposed by Gray (BIS-BAS) using exploratory factor analysis. Results showed two different components. One component was defined by the subscales sensitivity to reinforcement, positive urgency, negative urgency and sensation seeking. The second component was defined by the subscales sensitivity to punishment, lack of perseverance and lack of premeditation. PMID- 27391845 TI - Cross-cultural examination of the five-factor model of drinking motives in Spanish and Canadian undergraduates. AB - This study aims to test the cross-cultural suitability of Modified Drinking Motives Questionnaire-Revised (M DMQ-R) (Grant, Stewart, O'Connor, Blackwell, & Conrod, 2007). The sample included 571 Spanish and 571 Canadian undergraduates between the ages of 18 and 22 (65.8% women). The confirmatory factor analysis demonstrated factorial invariance between samples. The regression analysis showed that social, enhancement and low conformity motives were related to drinking frequency and drinking quantity in the total sample. No moderation effect of country on predicting alcohol consumption was found. The results suggest that M DMQ-R is a suitable instrument for comparing drinking motives across Spanish and Canadian undergraduates, and that motives-focused prevention and treatment programmes developed in one country could be generalised to another. PMID- 27391846 TI - Applied Prevalence Ratio estimation with different Regression models: An example from a cross-national study on substance use research. AB - OBJECTIVE: To examine the differences between Prevalence Ratio (PR) and Odds Ratio (OR) in a cross-sectional study and to provide tools to calculate PR using two statistical packages widely used in substance use research (STATA and R). METHODS: We used cross-sectional data from 41,263 participants of 16 European countries participating in the Survey on Health, Ageing and Retirement in Europe (SHARE). The dependent variable, hazardous drinking, was calculated using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C). The main independent variable was gender. Other variables used were: age, educational level and country of residence. PR of hazardous drinking in men with relation to women was estimated using Mantel-Haenszel method, log-binomial regression models and poisson regression models with robust variance. These estimations were compared to the OR calculated using logistic regression models. RESULTS: Prevalence of hazardous drinkers varied among countries. Generally, men have higher prevalence of hazardous drinking than women [PR=1.43 (1.38-1.47)]. Estimated PR was identical independently of the method and the statistical package used. However, OR overestimated PR, depending on the prevalence of hazardous drinking in the country. CONCLUSIONS: In cross-sectional studies, where comparisons between countries with differences in the prevalence of the disease or condition are made, it is advisable to use PR instead of OR. PMID- 27391847 TI - Gender differences in success at quitting smoking: Short- and long-term outcomes. AB - Smoking cessation treatments are effective in men and women. However, possible sex-related differences in the outcome of these treatments remain a controversial topic. This study evaluated whether there were differences between men and women in the success of smoking cessation treatment, including gender-tailored components, in the short and long term (> 1 year). A telephone survey was carried out between September 2008 and June 2009 in smokers attended in a Smoking Cessation Clinic. All patients who have successfully completed treatment (3 months) were surveyed by telephone to determine their long-term abstinence. Those who remained abstinent were requested to attend the Smoking Cessation Clinic for biochemical validation (expired CO <=10 ppm). The probability of remaining abstinent in the long-term was calculated using a Kaplan-Meier survival analysis. The treatment success rate at 3-months was 41.3% (538/1302) with no differences by sex 89% (479/538) among those located in the telephonic follow-up study and 47.6% (256/479) were abstinent without differences by sex (p = .519); abstinence was validated with CO less than 10 ppm in 191 of the 256 (53.9% men and 46.1% women). In the survival analysis, the probability of men and women remaining abstinent in the long-term was not significant. There are no differences by sex in the outcome of smoking cessation treatment that included gender-tailored components in the short and long term (> 1 year). PMID- 27391848 TI - Association between bullying victimization and substance use among college students in Spain. AB - The purpose of this study is to analyze the prevalence and association between victimization and substance use among the university population in the southeast of Spain in a sample of 543 randomly selected college students (405 females and 138 males with an average age of 22.6 years). As a cross-sectional study, data was collected through an anonymous survey to assess victimization and drug use over the last 12 months. Results indicated that 62.2% of college students reported bullying victimization and 82.9% consumed some type of psychoactive substance, and found a statistically significant association between both variables measured. Additionally, logistic regression analysis confirmed the association between psychoactive substance use and different types of victimization. Our findings confirm the need for prevention to prevent this relation between victimization and substance use. PMID- 27391849 TI - Orally ingestion of krokodil in Spain: report of a case. AB - The krokodil use disorder is an addictive pathology with quite severe organic effects, especially at the skin level, that causes severe and degenerative necrosis of blood and muscle tissue. Though this disorder has a low prevalence in Spain, compared to the large number of consumers in other countries such as Ukraine or Russia, its consumption is slowly but gradually expanding in countries of the European Union and America. The simplicity of the process of obtaining the substance from desomorphine, together with its high availability and low cost, contribute toward consumers' self-sufficiency. This article presents the case of a user of krokodil and reviews the clinical symptoms of oral ingestion. PMID- 27391850 TI - Gender differences in addiction severity. AB - Gender has been associated with substance use disorders (SUD). However, there are few studies that have evaluated gender differences in a global and a standardized way, and with a large sample of patients with SUD. Our goal is to analyze the role of gender in addiction severity throughout multiple life domains, using the Addiction Severity Index-6 (ASI-6). A naturalistic, multicenter and prospective study was conducted. A total of 221 patients with SUD (80.1% men) were interviewed with the ASI-6. Our results indicate that the Recent Summary Scores (RSSs) of men and women are similar, with the exception of Psychiatric and Partner- Problems, where women showed higher severity (p = .017 and p = .013, respectively). Statistically significant gender differences were found in certain aspects of the ASI-6 domains: men have more problems of physical health, legal issues, and alcohol and other substance use; and woman score higher in problems of mental health, social network, subjective evaluations of SUD consequences, and treatment needs. These results should be taken into account to improve the identification, prevention, and treatment of SUD. PMID- 27391851 TI - Alcohol, poverty and social exclusion: Alcohol consumption among the homeless and those at risk of social exclusion in Madrid. AB - The work analyzes different aspects related to alcohol consumption among homeless people and people at risk of social exclusion. The data was gathered from a representative sample of homeless people in Madrid (n = 188) and a sample of people at risk of social exclusion (n = 164) matched in sex, age, and origin (Spaniards vs. foreigners). The results showed that homeless people present a greater consumption of alcohol and have experienced more problems derived from its consumption than people at risk of social exclusion. Most of the homeless people who had alcohol-related problems had had them prior to their homelessness, and they stated they had poorer health and had experienced a greater number of homelessness episodes. Despite the relevance of problems related to alcohol among our sample, only a small percentage of the sample had participated in treatment programs for alcohol consumption. PMID- 27391852 TI - Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non prescribed drugs. AB - The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy. Some authors maintain that only doses higher than 50-60 mg/day ought to be considered effective, since only these block all the opioid receptors. But others propose the use of doses adjusted to the needs of the patient, based on their recovery process. Quality of life, satisfaction with treatment, psychopathological symptoms, cognitive performance and additional intake of illegal and unprescribed drugs were evaluated in a representative sample of all patients treated with opioid agonists in the Addiction Institute of Madrid (N = 1898, n = 450) and the Junta de Extremadura (N = 100, n = 65). The results revealed a negative relationship between dose and quality of life, psychopathological symptoms and cognitive performance. Satisfaction with treatment, based on doses negotiated together by doctor and patient, was very high, regardless of the dose. To establish hypothetical causal dependencies among the studied variables structural equation modelling was performed. The results reject the need for high dosage if not required by the patient, and highlight the benefits of other psychosocial interventions that lead to recovery, despite the chronification that could imply the use of high doses. Whereas high dosage programmes provide better indicators of social control, the patient's quality of life must be one of the main indicators of a successful treatment, as in any other health problem. PMID- 27391853 TI - Methadone for the treatment of Prescription Opioids Dependence. A retrospective chart review. AB - Prescription opioids (PO) addiction is increasing to an epidemic level. Few studies exist regarding its treatment. Although buprenorphine has been the mainstay so far, other treatment options might be considered, such as methadone. We conducted a retrospective assessment of all patients admitted to a psychiatry ward for PO detoxification using methadone between 2010 and 2013. The assessment and description was carried out during a 3-month follow-up period after their discharge. Although this is a retrospective chart review, our exploration included sociodemographic and treatment variables in addition to the abstinence rates for the whole sample. Eleven patients were included, mostly women (81.8%), with a median age of 50 years. The median duration of dependence was 8 years. Dependence on other substances and psychiatric comorbidities were high. Eight patients were monitored during three months. Of these, 7 (87.5%) were abstinent after that period. The results suggest that methadone deserves further exploration as a potentially efficacious treatment option for PO dependence. PMID- 27391854 TI - Psychopathic Traits and Their Relationship with the Cognitive Costs and Compulsive Nature of Lying in Offenders. AB - The cognitive view on deception holds that lying typically requires additional mental effort as compared to truth telling. Psychopathy, however, has been associated with swift and even compulsive lying, leading us to explore the ease and compulsive nature of lying in psychopathic offenders. We explored the costs of instructed lying versus truth telling through RTs and error rates in 52 violent male offenders, who were assessed with the Youth Psychopathic Traits Inventory (YPI). Our deception paradigm also included trials with the free choice to lie or tell the truth. By coupling monetary loss to slow and erroneous responding, we hypothesized that the frequency of lying despite likely negative consequences, would provide an index of compulsive lying. Offenders were slower and erred more often when lying than when telling the truth, and there was no robust association between psychopathy and the cognitive cost of lying. From an applied perspective, this suggests that psychopathy may not threaten the validity of computerized cognition-based lie detection. In the face of probable negative consequences, high grandiose-manipulative offenders chose to lie three times as often as low grandiose-manipulative offenders. Our new lying frequency index is a first attempt to create a much needed tool to empirically examine compulsive lying, and provides preliminary support for the compulsive nature of lying in grandiose-manipulative offenders. Alternative interpretation of the findings are discussed. PMID- 27391855 TI - Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism. AB - Lysophospholipase-like 1 (LYPLAL1) is an uncharacterized metabolic serine hydrolase. Human genome-wide association studies link variants of the gene encoding this enzyme to fat distribution, waist-to-hip ratio, and nonalcoholic fatty liver disease. We describe the discovery of potent and selective covalent small-molecule inhibitors of LYPLAL1 and their use to investigate its role in hepatic metabolism. In hepatocytes, selective inhibition of LYPLAL1 increased glucose production supporting the inference that LYPLAL1 is a significant actor in hepatic metabolism. The results provide an example of how a selective chemical tool can contribute to evaluating a hypothetical target for therapeutic intervention, even in the absence of complete biochemical characterization. PMID- 27391856 TI - PAH and OPAH Flux during the Deepwater Horizon Incident. AB - Passive sampling devices were used to measure air vapor and water dissolved phase concentrations of 33 polycyclic aromatic hydrocarbons (PAHs) and 22 oxygenated PAHs (OPAHs) at four Gulf of Mexico coastal sites prior to, during and after shoreline oiling from the Deepwater Horizon oil spill (DWH). Measurements were taken at each site over a 13 month period, and flux across the water-air boundary was determined. This is the first report of vapor phase and diffusive flux of both PAHs and OPAHs during the DWH. Vapor phase sum PAH and OPAH concentrations ranged between 6.6 and 210 ng/m(3) and 0.02 and 34 ng/m(3) respectively. PAH and OPAH concentrations in air exhibited different spatial and temporal trends than in water, and air-water flux of 13 individual PAHs was shown to be at least partially influenced by the DWH incident. The largest PAH volatilizations occurred at the sites in Alabama and Mississippi at nominal rates of 56 000 and 42 000 ng/m(2) day(-1) in the summer. Naphthalene was the PAH with the highest observed volatilization rate of 52 000 ng/m(2) day(-1) in June 2010. This work represents additional evidence of the DWH incident contributing to air contamination, and provides one of the first quantitative air-water chemical flux determinations with passive sampling technology. PMID- 27391857 TI - The Efficacy of Gynura pseudochina DC. var. hispida Thv. Ointment in Treating Chronic Plaque Psoriasis: A Randomized Controlled Trial. AB - BACKGROUND: A recent study showed that Gynura pseudochina DC. var. hispida Thv. leaf extract (GP) can reduce the activation of the nuclear factor kappaB (NF kappaB) pathway and suppress the release of interleukin (IL)-1beta, IL-6, and tumor necrosis factor -alpha, which play an important role in the pathogenesis of psoriasis. METHODS: Twenty-five patients with mild to moderate plaque psoriasis completed a 4-week trial. Twice daily, they applied the GP ointment on psoriatic lesions on one side of the body, and they applied 0.1% triamcinolone (TA) cream on the other side. The Targeted Area Score (TAS), Psoriasis Severity Index (PSI) scores, and Physician's Global Assessment (PGA) scores were assessed at baseline and at weeks 1, 2, 3, and 4. Pre- and post-treatment skin samples were taken. Phosphorylation of NF-kappaB p65, Ki-67, and epidermal thickness were analyzed through immunohistochemistry. RESULTS: The TAS for erythema, scaling, and induration and PSI scores decreased on both treated sides. A statistically significant difference was observed beginning at the first week of treatment. The GP ointment significantly decreased scaling scores. However, no significant differences were observed between the TAS for erythema and induration or the PSI and PGA scores. Immunohistochemical staining revealed diminution of phosphorylated NF-kappaB p65, Ki-67, and epidermal thickness in the lesions treated with the GP ointment. The ointment was well tolerated, with minimal side effects. No laboratory abnormalities were detected. CONCLUSIONS: The GP ointment demonstrated efficacy similar to that of 0.1% TA cream for mild to moderate chronic plaque psoriasis. In addition, its short-term side effects were minimal. PMID- 27391858 TI - Spatial Heterogeneity of Leaf Area Index (LAI) and Its Temporal Course on Arable Land: Combining Field Measurements, Remote Sensing and Simulation in a Comprehensive Data Analysis Approach (CDAA). AB - The ratio of leaf area to ground area (leaf area index, LAI) is an important state variable in ecosystem studies since it influences fluxes of matter and energy between the land surface and the atmosphere. As a basis for generating temporally continuous and spatially distributed datasets of LAI, the current study contributes an analysis of its spatial variability and spatial structure. Soil-vegetation-atmosphere fluxes of water, carbon and energy are nonlinearly related to LAI. Therefore, its spatial heterogeneity, i.e., the combination of spatial variability and structure, has an effect on simulations of these fluxes. To assess LAI spatial heterogeneity, we apply a Comprehensive Data Analysis Approach that combines data from remote sensing (5 m resolution) and simulation (150 m resolution) with field measurements and a detailed land use map. Test area is the arable land in the fertile loess plain of the Rur catchment on the Germany Belgium-Netherlands border. LAI from remote sensing and simulation compares well with field measurements. Based on the simulation results, we describe characteristic crop-specific temporal patterns of LAI spatial variability. By means of these patterns, we explain the complex multimodal frequency distributions of LAI in the remote sensing data. In the test area, variability between agricultural fields is higher than within fields. Therefore, spatial resolutions less than the 5 m of the remote sensing scenes are sufficient to infer LAI spatial variability. Frequency distributions from the simulation agree better with the multimodal distributions from remote sensing than normal distributions do. The spatial structure of LAI in the test area is dominated by a short distance referring to field sizes. Longer distances that refer to soil and weather can only be derived from remote sensing data. Therefore, simulations alone are not sufficient to characterize LAI spatial structure. It can be concluded that a comprehensive picture of LAI spatial heterogeneity and its temporal course can contribute to the development of an approach to create spatially distributed and temporally continuous datasets of LAI. PMID- 27391859 TI - Biomarkers Capable to Early Predict Postoperative Complications: The Grail. PMID- 27391860 TI - Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study. AB - PURPOSE: Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. MATERIALS AND METHODS: Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy whole-mount histopathology produced with patient-specific three dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. RESULTS: Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS >= 3 and 90% for PIRADS >= 4. Specialists performed better only for PIRADS >= 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. CONCLUSION: By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:579-585. PMID- 27391861 TI - Re-manufacture of cobalt-manganese-bromide as a liquid catalyst from spent catalyst containing cobalt generated from petrochemical processes via hydrometallurgy. AB - Cobalt and manganese have been the subject of individual separation studies because their fields of application are different. However, this study shows that high-value products can be manufactured in the form of a cobalt-manganese-bromide (CMB) liquid catalyst by simultaneously recovering cobalt and manganese. Na-bis (2,4,4-tri-methyl-pentyl)phosphinic acid was employed in order to manufacture the CMB liquid catalyst from the spent catalyst generated from petroleum chemistry processes. The pH-isotherm, degree of saponification of solvent and separation factor values were investigated. DeltapH50 and separation factor values show that Co and Mn can be separated from impurities such as Mg and Ca. Further, the extraction stages and organic/aqueous ratio isotherms were investigated using counter-current simulation extraction batch tests. To prepare CMB from a loaded organic phase obtained in a stripping study using hydrogen bromide, the Co and Mn were completely stripped and concentrated by a factor of 6 using a 2M hydrogen bromide solution. When compared with manufactured and commercial CMB, the CMB liquid catalyst could be produced by supplying a shortage of Mn in the form of manganese bromide. Finally, the method of manufacture of CMB was subjected to a real pilot plant test. PMID- 27391862 TI - PAH emissions from coal combustion and waste incineration. AB - The characteristics of PAHs that are emitted by a municipal waste incinerator (MWI) and coal-fired power plant are examined via intensive sampling. Results of flue gas sampling reveal the potential for PAH formation within the selective catalytic reduction (SCR) system of a coal-fired power plant. In the large-scale MWI, the removal efficiency of PAHs achieved with the pilot-scaled catalytic filter (CF) exceeds that achieved by activated carbon injection with a bag filter (ACI+BF) owing to the effective destruction of gas-phase contaminants by a catalyst. A significantly lower PAH concentration (1640ng/g) was measured in fly ash from a CF module than from an ACI+BF system (5650ng/g). Replacing the ACI+BF system with CF technology would significantly reduce the discharge factor (including emission and fly ash) of PAHs from 251.6 to 77.8mg/ton-waste. The emission factors of PAHs that are obtained using ACI+BF and the CF system in the MWI are 8.05 and 7.13mg/ton, respectively. However, the emission factor of MWI is significantly higher than that of coal-fired power plant (1.56mg/ton). From the perspective of total environmental management to reduce PAH emissions, replacing the original ACI+BF process with a CF system is expected to reduce environmental impact thereof. PMID- 27391863 TI - Degradation rates of phorbol esters in Jatropha curcas L. oil and pressed seeds under different storage conditions. AB - BACKGROUND: Phorbol esters (PEs), found in Jatropha curcas crude oil (JCO) and J. curcas pressed seeds (JPS), are known as bioactive compounds in agricultural and pharmaceutical applications. The degradation rates of PEs in JCO and JPS under various conditions is important for the utilisation of PEs. Thus the objective of this study was to determine the PE degradation rates in JCO and JPS under different storage conditions. RESULTS: PE degradation rates were found to be first-order reactions. The slowest degradation rate was at 0.9 * 10-3 d-1 for both JCO and JPS unexposed to light at 4 degrees C. Light intensity (1097 lx and 4690 lx, representing diffused sunlight and fluorescent lighting, respectively) and temperature (25 to 35 degrees C) were the significant degradation factors. Light exposure led to 280% to 380% higher degradation rates in JCO than in JPS due to light penetration through the transparent oil. Dried and sterilised JPS showed an 80% to 90% lower PE degradation rate than untreated JPS under all storage conditions since biodegradation was assembly limited. CONCLUSION: The PEs were unstable under the studied conditions, especially when exposed to light and room temperature. To protect against PE degradation, a material should be stored in a light-protected container and below 4 degrees C. (c) 2016 Society of Chemical Industry. PMID- 27391864 TI - Okara (soybean residue) biotransformation by yeast Yarrowia lipolytica. AB - Okara, or soybean residue, is a soy food processing by-product from the manufacture of soymilk and soybean curd (tofu). In this study, solid-state fermentation of okara was conducted over 5days using yeast Yarrowia lipolytica, and the changes in proximate composition, antioxidant capacity, non-volatiles and volatiles were investigated. Yeast metabolism of okara significantly increased the amounts of lipid, succinate and free amino acids and enhanced the antioxidant capacity. In particular, there was a marked increase in important umami tastants after fermentation, with 3-fold increase in succinate and a 20-fold increase in glutamate. The final fermented okara contained 3.37g succinate and 335mg glutamate/100g dry matter. Aldehydes and their derived acids in the fresh okara were catabolised by Y. lipolytica mainly to methyl ketones, leading to a reduced grassy off-odour and a slightly pungent, musty and cheese-like odour in the fermented okara. Amino acid-derived volatiles, such as 3-methylbutanal and 2 phenylethanol, were also produced. Overall, the okara fermented by Y. lipolytica had a greater amount of umami-tasting substances, a cheese-like odour, improved digestibility and enhanced antioxidant capacity. These changes highlight the potential of Yarrowia-fermented okara as a more nutritious, savoury food product or ingredient. Y. lipolytica was thus demonstrated to be suitable for the biovalorisation of this soy food processing by-product. PMID- 27391865 TI - Spin- and angle-resolved photoemission on the topological Kondo insulator candidate: SmB6. AB - Topological Kondo insulators are a new class of topological insulators in which metallic surface states protected by topological invariants reside in the bulk band gap at low temperatures. Unlike other 3D topological insulators, a truly insulating bulk state, which is critical for potential applications in next generation electronic devices, is guaranteed by many-body effects in the topological Kondo insulator. Furthermore, the system has strong electron correlations that can serve as a testbed for interacting topological theories. This topical review focuses on recent advances in the study of SmB6, the most promising candidate for a topological Kondo insulator, from the perspective of spin- and angle-resolved photoemission spectroscopy with highlights of some important transport results. PMID- 27391866 TI - Genomics of the Effect of Spinal Cord Stimulation on an Animal Model of Neuropathic Pain. AB - BACKGROUND: Few studies have evaluated single-gene changes modulated by spinal cord stimulation (SCS), providing a narrow understanding of molecular changes. Genomics allows for a robust analysis of holistic gene changes in response to stimulation. METHODS: Rats were randomized into six groups to determine the effect of continuous SCS in uninjured and spared-nerve injury (SNI) animals. After behavioral assessment, tissues from the dorsal quadrant of the spinal cord (SC) and dorsal root ganglion (DRG) underwent full-genome microarray analyses. Weighted Gene Correlation Network Analysis (WGCNA), and Gene Ontology (GO) analysis identified similar expression patterns, molecular functions and biological processes for significant genes. RESULTS: Microarray analyses reported 20,985 gene probes in SC and 19,104 in DRG. WGCNA sorted 7449 SC and 4275 DRG gene probes into 29 and 9 modules, respectively. WGCNA provided significant modules from paired comparisons of experimental groups. GO analyses reported significant biological processes influenced by injury, as well as the presence of an electric field. The genes Tlr2, Cxcl16, and Cd68 were used to further validate the microarray based on significant response to SCS in SNI animals. They were up regulated in the SC while both Tlr2 and Cd68 were up-regulated in the DRG. CONCLUSIONS: The process described provides highly significant interconnected genes and pathways responsive to injury and/or electric field in the SC and DRG. Genes in the SC respond significantly to the SCS in both injured and uninjured animals, while those in the DRG significantly responded to injury, and SCS in injured animals. PMID- 27391867 TI - Current treatment options for esophageal diseases. AB - Exciting new developments-pharmacologic, endoscopic, and surgical-have arisen for the treatment of many esophageal diseases. Refractory gastroesophageal reflux disease presents a therapeutic challenge, and several new options have been proposed to overcome an insufficient effectiveness of proton pump inhibitors. In patients with distal esophageal spasm, drugs and endoscopic treatments are the current mainstays of the therapeutic approach. Treatment with proton pump inhibitors (or antireflux surgery) should be considered in patients with Barrett's esophagus, since a recent meta-analysis demonstrated a 71% reduction in risk of neoplastic progression. Endoscopic resection combined with radiofrequency ablation is the standard of care in patients with early esophageal adenocarcinoma. Mucosal squamous cancer may also be treated endoscopically, preferably with endoscopic submucosal dissection. Patients with upper esophageal cancer often refrain from surgery. Robot-assisted, thoracolaparoscopic, minimally invasive esophagectomy may be an appropriate option for these patients, as the robot facilitates a good overview of the upper mediastinum. Induction chemoradiotherapy is currently considered as standard treatment for patients with advanced squamous cell carcinoma, while the role of neoadjuvant therapy for adenocarcinoma remains controversial. A system for defining and recording perioperative complications associated with esophagectomy has been recently developed and may help to find predictors of mortality and morbidity. PMID- 27391868 TI - Red blood cell membrane fatty acid composition in infants fed formulas with different lipid profiles. AB - BACKGROUND: There is growing interest in the fatty acid composition of breast milk and substitute formulas used to replace or complement infant breastfeeding. AIM: The aims of this study were to assess the impact of two follow-up infant formulas based on cow milk fat, vegetable oils and different docosahexaenoic (DHA) and arachidonic (ARA) acid content on red blood cell membrane fatty acid composition, and determine the percent saturated fatty acid (SFA) incorporation into the membrane. STUDY DESIGN: This was a double-blind, randomized, controlled, parallel-group clinical trial. Infants received treatment or control product for at least four months before the age of six months. The control group (n=25) received standard infant formula (FA) and the treatment group (n=24) received the same formula supplemented with higher DHA and ARA content (FB). The reference group (n=47) consisted of normal healthy exclusively breastfed infants. OUTCOME MEASURE: Red blood cell membrane fatty acid composition was determined by capillary gas chromatography. RESULTS: Ninety-six infants completed the study (FA, 25; FB, 24; reference, 47). Higher DHA content reflected higher DHA percentage in the red blood cell membrane. Breast milk and FB did not show any significant differences in DHA content. ARA percentage was higher in breastfed infants and palmitic acid percentage was higher in FB- compared with FA-fed infants. CONCLUSION: DHA and palmitic acid percent distributions were higher in the red blood cell membrane of infants receiving FB. DHA percent distribution was not significantly different in FB-fed and breastfed infants. SFA percent distribution was not significantly different when comparing both formulas with breast milk. PMID- 27391869 TI - Obstetric and perinatal outcomes in women >=40years of age: Associations with fetal growth disorders. AB - BACKGROUND: Evidence indicates that advanced maternal age is associated with adverse obstetric and perinatal outcomes. The purpose of this study was to evaluate pregnancy outcomes in women of advanced maternal age (>=40years). METHODS: Using a prospective study design, data were collected by the Department of Obstetrics at the San Joan de Deu Hospital of Barcelona during the 1 June 2009 to 31 May 2012 period. The results were compared across three maternal age groups (>=40 [n=654], 35-39 [n=2781], and <35 [n=7893] years). RESULTS: Of the 11328 births recorded during the study period, pregnancy-related complications were more common in women >=40years of age. The most common disorder was diabetes (8.5% in the >=40, 5.3% in the 35-39, and 3.0% in the <35years age groups). The women >=40years of age also had significantly more premature births (p=0.001) and cesarean sections (17% in the >=40, 12.5% in the 35-39, and 7.9% in the <35-year age groups; p=0.001). Intrauterine growth retardation was significantly more frequent in women aged >=40years (17.4% in the >=40, 15% in the 35-39, and 14.0% in the <35-year age groups; p=0.03). Fetal macrosomia was significantly more common in women >=40years (15.4% in the >=40, 12.6% in the 35-39, and 12% in the <35-year age groups; p=0.03). CONCLUSION: Maternal age >=40years was associated with poorer obstetric and perinatal outcomes and increased the risks of cesarean section, intrauterine growth retardation, and fetal macrosomia. PMID- 27391871 TI - Early and intensive nutritional strategy combining parenteral and enteral feeding promotes neurodevelopment and growth at 18months of corrected age and 3years of age in extremely low birth weight infants. AB - AIM: To evaluate whether aggressive nutrition can improve long-term neurodevelopmental outcomes and growth in extremely low birth weight (ELBW) infants born appropriate for gestational age (AGA). METHODS: This single-center cohort study included 137 ELBW AGA infants born in two epochs. The first group received standard nutrition (SN; n=79) consisting of amino acids started at 0.5g/kg/day on Day 4 of life and increased to 1.0g/kg/day. The second aggressive nutrition (AN) group received amino acids started at 1.5-2.0g/kg/day within 24h of life and increased to 3.5g/kg/day. Parenteral and enteral feedings were combined in both groups. Neurodevelopmental outcomes by the Kyoto Scale of Psychological Development and growth were followed up to 18months of corrected age or 3years of age and compared by univariate and multivariate analyses. RESULTS: Baseline characteristics were similar between the two groups. At 3years of age, AN children had a significantly greater mean value of head circumference, but not length or weight, than SN children (49.1 vs 48.0cm, p=0.014). The cognitive-adaptive (C-A) score in the AN group was also significantly higher than that in the SN group (98.3 vs 91.9 at 18months, p=0.039 and 89.5 vs 83.1 at 3years, p=0.047). AN infants born >=26weeks of gestation were less likely to develop borderline disability in C-A, language-social and overall developmental scores compared to gestational age-matched SN infants. CONCLUSION: Parenteral and enteral AN after birth improved the long-term cognitive neurodevelopment in ELBW AGA infants, especially in those born >=26weeks of gestational age, however results need to be confirmed in a larger, multi-site randomized trial. PMID- 27391870 TI - Very low birth weight infants in China: the predictive value of the motor repertoire at 3 to 5months for the motor performance at 12months. AB - BACKGROUND: Studies on motor performance and its early markers are rare in China, especially in very low birth weight (VLBW) infants. OBJECTIVE: Apart from the assessment of the inter-scorer agreement, we aimed to analyze to what extent the motor repertoire at 10 to 18weeks postterm was related to neonatal complications, and gross and fine motor performance at 12months after term. STUDY DESIGN: Exploratory prospective study. SUBJECTS: Seventy-four VLBW infants (58 males; mean gestational age=29weeks; mean birth weight=1252g). METHOD: Five-minute video recordings were performed at 10 to 18weeks after term; fidgety movements and the concurrent motor patterns (resulting in a motor optimality score) were assessed according to the Prechtl general movements assessment (GMA). The gross and fine motor performance was assessed by means of the Peabody Developmental Motor Scales, second edition, at 12months. RESULTS: Reliability was excellent. Pneumonia was associated with absent fidgety movements; the motor optimality score was lower in infants with pneumonia and/or bronchopulmonary dysplasia. Both absent fidgety movements and a lower motor optimality score were associated with a poor or very poor gross and fine motor performance at the 12-month-assessment. CONCLUSION: Both the assessment of fidgety movements and the evaluation of the concurrent motor repertoire contribute significantly to an identification of VLBW children with a poor gross and fine motor outcome at 12months. The results of this study document the need for an early identification of infants at high risk for a poor motor performance. PMID- 27391872 TI - Interferon-gamma reduces the proliferation of M. tuberculosis within macrophages from a patient with a novel hypomorphic NEMO mutation. AB - X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by mutations in the nuclear factor-kappa B essential modulator (NEMO) gene. Here, we report the clinical and genetic features of a XL-EDA-ID patient who developed bacillus Calmette-Guerin infection. Patient lymphocytes failed to degrade IkappaB alpha, and sequencing of NEMO identified the novel mutation c.1238A>C/p.H413P. Furthermore, patient monocyte-derived macrophages ingested Mycobacterium tuberculosis normally, but failed to control the intracellular proliferation of bacilli, a defect which was improved in the presence of interferon-gamma (IFN gamma). This work expands the genetic spectrum of XL-EDA-ID and demonstrates improvement in macrophage function in a NEMO-deficient patient by IFN-gamma. PMID- 27391874 TI - Report from the Alzheimer's Research UK Conference 2015. AB - On 10-11 March 2015 University College London hosted the annual Alzheimer's Research UK Conference. This report provides an overview of the presentations and discussions that took place. PMID- 27391873 TI - Stereoacuity and Related Factors: The Shandong Children Eye Study. AB - OBJECTIVE: To assess stereoacuity in a population-based sample of children and to examine ocular and systemic parameters related to stereoacuity. METHODS: Using a random cluster sampling method, four- to 18-year-old children from kindergartens, elementary schools, junior high schools and senior high schools from a rural area and an urban area in the East Chinese province of Shandong were included in the school-based cross-sectional study. All participants underwent a comprehensive eye examination including assessment of cycloplegic refraction and measurement of stereoacuity using the Titmus Stereo test. RESULTS: Out of 6364 eligible children, 5780 (90.8%) children with a mean age of 10.1 +/- 3.2 years (range: 4 to 18 years) participated. Mean (+/- standard deviation) stereoacuity was 50.2 +/ 50.6 arc seconds. Stereoacuity improved significantly (P<0.01) from the age group of 4 years to the age group of 6 to 7 years, then showed a plateau, deteriorated (P = 0.001) for both sexes from the age group of 9 years to the age group of 12 years (P<0.001), after which it improved (P = 0.001) again in the age group of 16 years or older to the pre-puberty values. In multivariate analysis, larger angle of binocular disparity (i.e., lower stereoacuity) was significantly associated with lower best corrected visual acuity (logMAR; P<0.001), higher intereye difference in refractive error (spherical equivalent) (P<0.001), higher cylindrical refractive error (P<0.001), higher refractive error (spherical value; P<0.001), higher intereye difference in best corrected visual acuity (logMAR) (P = 0.001), higher intereye difference in axial length (P = 0.001), and rural region of habitation (P = 0.006). CONCLUSIONS: Stereoacuity as tested with the Titmus Stereo test improved significantly from an age of 4 years to an age of 6 and 7 years, then remained constant, temporarily deteriorated for both sexes in pre-puberty and puberty, after which it improved again to pre-puberty or better values at the age of 16 years or older. Lower stereoacuity was associated with lower best corrected visual acuity and higher intereye difference in best corrected visual acuity, higher cylindrical and spherical refractive errors, higher inter-eye difference in refractive error, higher intereye difference in axial length, and rural region of habitation. PMID- 27391875 TI - Correlation between changes in liver stiffness and preeclampsia as shown by transient elastography. AB - OBJECTIVE: The aim of this study was to evaluate the use of Fibroscan as a measure of liver transient elastography in women with preeclampsia and compare the results with a group of normotensive controls. MATERIALS AND METHODS: In this prospective observational case-control study, women at 24-41 weeks gestation who were diagnosed with preeclampsia using standard criteria, between January 2012 and December 2013, were included. The Fibroscan test was performed by a hepatologist 1-7 days postpartum. A control group consisted of low-risk women with normal pregnancy outcomes. RESULTS: Fibroscan results for fibrosis were significantly higher in the 32 preeclamptic women compared to the 16 normotensive women (mean 4.57 kPa vs. 3.66 kPa respectively, P = 0.01). There was no difference in liver steatosis between women with preeclampsia and normotensive women (226 vs. 225 kPa, respectively, P = 0.442) Conclusions: Fibroscan results for fibrosis were significantly higher in postpartum preeclamptic women (although within the normal range). Further studies are required in order to evaluate the usefulness of Fibroscan as an additional test in the evaluation and management of preeclampsia. PMID- 27391876 TI - Electric Switching of Fluorescence Decay in Gold-Silica-Dye Nematic Nanocolloids Mediated by Surface Plasmons. AB - Tunable composite materials with interesting physical behavior can be designed through integrating unique optical properties of solid nanostructures with facile responses of soft matter to weak external stimuli, but this approach remains challenged by their poorly controlled coassembly at the mesoscale. Using scalable wet chemical synthesis procedures, we fabricated anisotropic gold-silica-dye colloidal nanostructures and then organized them into the device-scale (demonstrated for square-inch cells) electrically tunable composites by simultaneously invoking molecular and colloidal self-assembly. We show that the ensuing ordered colloidal dispersions of shape-anisotropic nanostructures exhibit tunable fluorescence decay rates and intensity. We characterize how these properties depend on low-voltage fields and polarization of both the excitation and emission light, demonstrating a great potential for the practical realization of an interesting breed of nanostructured composite materials. PMID- 27391877 TI - Association between Progressive Intraventricular Conduction Disturbance and Cardiovascular Events. AB - BACKGROUND: Prolonged QRS duration on electrocardiogram (ECG) has been known as a poor prognostic marker. However, little is known about association between progressive intraventricular conduction disturbance and cardiovascular prognosis. METHODS: From among a database containing 359,737 12-lead ECG recordings, patients whose QRS duration progressively increased from <120 msec to >=120 msec were selected using software. The prognosis of patients was searched by medical record. The primary endpoint was defined as heart failure hospitalization. The secondary endpoint was heart failure hospitalization, device implantation, or cardiovascular death. RESULTS: A total of 143 patients (100 males; age, 58.9+/ 11.1 years) were enrolled in this study. QRS duration increased by 46.4+/-13.8 msec, manifesting right bundle branch block (RBBB) in 99 (69.2%) patients and non RBBB (i.e., left bundle branch block, RBBB with left anterior hemiblock, or nonspecific intraventricular conduction disturbance) in 44 (30.8%). During the follow-up (mean, 16.6+/-5.3 years), 44 (30.3%), 15 (10.3%), and 6 (4.1%) patients resulted in heart failure hospitalization, device implantation, and cardiovascular death, respectively. Multivariate Cox proportional hazards models revealed that 1) the temporal increase in QRS duration was associated with the primary endpoint (hazard ratio [HR] 1.98; 95% confidence interval [CI] 1.05-3.80; p = 0.04) and the secondary endpoint (HR 2.79; 95% CI 1.55-5.00; p = 0.0001) and 2) the development of non-RBBB was associated with the primary endpoint (HR 3.02; 95% CI 1.59-5.73; p = 0.0001) and the secondary endpoint (HR 2.82; 95% CI 1.57 5.09; p = 0.001). CONCLUSION: The temporal increase in QRS duration and the development of non-RBBB patterns were independently associated with adverse cardiovascular prognosis. PMID- 27391878 TI - A practical approach to the nutritional management of chronic kidney disease patients in Cape Town, South Africa. AB - BACKGROUND: The multi-racial and multi-ethnic population of South Africa has significant variation in their nutritional habits with many black South Africans undergoing a nutritional transition to Western type diets. In this review, we describe our practical approaches to the dietary and nutritional management of chronic kidney disease (CKD) patients in Cape Town, South Africa. DISCUSSION: Due to poverty and socio-economic constraints, significant challenges still exist with regard to achieving the nutritional needs and adequate dietary counselling of many CKD patients (pre-dialysis and dialysis) in South Africa. Inadequate workforce to meet the educational and counselling needs of patients, inability of many patients to effectively come to terms with changing body and metabolic needs due to ongoing kidney disease, issues of adherence to fluid and food restrictions as well as adherence to medications and in some cases the inability to obtain adequate daily food supplies make up some of these challenges. A multi disciplinary approach (dietitians, nurses and nephrologists) of regularly reminding and educating patients on dietary (especially low protein diets) and nutritional needs is practiced. The South African Renal exchange list consisting of groups of food items with the same nutritional content has been developed as a practical tool to be used by dietitians to convert individualized nutritional prescriptions into meal plan to meet the nutritional needs of patients in South Africa. The list is currently utilized in counselling CKD patients and provides varied options for food items within the same group (exchangeable) as well as offering ease for the description of suitable meal portions (sizes) to our patients. Regular and continuous education of CKD patients by a multi disciplinary team in South Africa enables our patients to meet their nutritional goals and retard CKD progression. The South African renal exchange list has proved to be a very useful tool in meeting this need. PMID- 27391879 TI - [Not Available]. PMID- 27391880 TI - [Parents support for the ban on television food advertising to children is particularly high in France, especially compared to the USA. This result should influence political decision-making to restrict food marketing targeting young people]. AB - INTRODUCTION: Massive exposure of children to low-nutrient food advertising combined with the increasing prevalence of obesity have led to growing support for statutory regulations concerning food marketing targeting children. Food and advertising industries lobbies have nevertheless managed to stop such measures in many countries. In this context, civil society support for statutory regulation, especially by parents, is essential. The objective of this study was to describe and analyse factors associated with parents' opinion on the impact and possible banning of food TV advertisements targeting children. METHODS: An online survey of 2,387 parents of children aged 3 to 17 was conducted in 2013. Associations between parents'opinion on food advertising and their socio-demographic characteristics were analysed by multivariate logistic regressions. RESULTS: The influence of food advertising on children' preferences was perceived by 64.7% of parents, 68.8% of parents were at least occasionally asked by their children to purchase food or beverages seen on television, 43.5% reported that their children influenced their food purchases and 73.7% supported a statutory regulation that would ban advertisements for excessively fatty, salty and sugary beverages and foods during television programmes for children or teenagers. This view was positively associated with high socio-economic status and a high perceived impact of advertising on children's food preferences. CONCLUSION: Parents support for the ban on television food advertising to children is particularly high in France, especially compared to the USA. This result should influence political decision-making to restrict food marketing targeting young people. PMID- 27391881 TI - [The commitment of French general practitioners to vaccination: the DIVA study (Determinants of Vaccination Intentions)]. AB - OBJECTIVES: Vaccination is an effective way to reduce morbidity and mortality related to infectious diseases. In France, primary care physicians are the main administrators of vaccines. Our objective was to conduct an exploratory qualitative study with primary care physicians to identify determinants of their commitment to vaccination. METHODS: A qualitative research study was conducted with 36 primary care physicians from different geographical regions in France. Six focus group discussions, following a semi-structured interview guide, were held. Qualitative analysis based on coding of the transcribed discussions was performed to identify the factors influencing primary care physicians' attitudes toward vaccination. These factors were then organized into themes. Saturation was also evaluated. RESULTS: Diphtheria, tetanus, poliomyelitis, measles, mumps, rubella, hepatitis B, tuberculosis, pneumococcal infections, meningococcus, human papillomavirus, rotavirus, pertussis, varicella and flu vaccinations were all discussed in each focus group. Saturation was reached from the fourth focus group. Forty identified determinants were divided into six themes: vaccine characteristics, disease characteristics, primary care physicians' past experience, practical aspects, expected benefits and primary care physician patient relationship. CONCLUSIONS: This study identified the behavioural and organizational determinants influencing primary care physicians' attitudes toward vaccination. These attitudes and determinants varied according to diseases and vaccines. The identified determinants and themes were used as a basis for the development of a questionnaire evaluating the Determinant of Vaccination Intentions (DIVA) of primary care physicians. PMID- 27391882 TI - [Training session on healthy environments: evaluation of an intervention for local stakeholders]. AB - BACKGROUND: Around the world, various interventions have been developed to encourage the adoption of healthy lifestyles, particularly nutrition and physical activity. Physical, political, economic and socio-cultural environments have a major influence on individual attitudes in relation to healthy lifestyle. However, stakeholders with the greatest impact on improving these environments are not always well informed about the theory and their roles on the creation of environments favourable to healthy lifestyles. Various stakeholders from the province of Quebec were therefore invited to attend training sessions in order to prepare them to act on these four environments. OBJECTIVES: 1) To describe the perceptions of the stakeholders who attended these sessions concerning the content and teaching methods and 2) to identify stakeholders' changes of perceptions and practices following the training session. METHODS: Twelve (12) focus groups and 52 individual interviews were conducted across Quebec with stakeholders who attended a training session. RESULTS: Our results indicate increased awareness of stakeholders on the importance of their role but also the need to more precisely target those aspects requiring increased awareness. A content better suited to the level of expertise is therefore proposed to maximize the benefits of these training sessions. CONCLUSION: Training sessions must be addressed to influential stakeholders with a limited knowledge on the subject, which is often the case for municipal decision-makers known to play a major role in promoting environments favourable to healthy eating and physical activity. PMID- 27391883 TI - [Nudge in prevention... an alternative approach or a dead end?]. AB - Prevention policies need to be more effective. Practitioners and decision-makers therefore need to innovate in the field of prevention policies and interventions by adapting methods or strategies used in other domains. Nudges, considered to be an attractive technique in view of its efficacy, are one of these innovations.However, the use of nudges in prevention policies raises ethical debates which will be summarized in this article. After recalling the definition of nudging, this article describes the ethical debates concerning three issues and emphasizes the way they can reflect a beneficial, democratic, freedom-based and autonomous society.In conclusion, this article encourages prevention practitioners and decision-makers to adopt a larger view before transferring strategies from other sectors and especially to consider all ethical issues. PMID- 27391884 TI - [Implementing a "Health Promoting Workplace": compatible organizational practices in university hospital]. AB - In 2006, a University Hospital in Quebec decided to implement the Health Promoting Hospital project (HPH). A study was conducted on the internal context of the HPH Project implementation, and more particularly on one of its dimensions, the "health promoting workplace". Compatibility is an important factor of the internal context, but has been rarely studied. The objective of this paper is to examine whether there are any organizational practices compatible with those of a health promoting workplace for nurses. A questionnaire was administered, interviews were conducted with strategic actors and a document analysis was performed.The results show various levels of compatibility with the criteria of a health promoting workplace. Thus, compatibility was very high for criteria related to the development of a learning and efficient organization, the strategies to ensure a healthy and safe workplace, and healthy lifestyles. However, poor compatibility was observed for criteria related to the adoption of a health promotion policy and no compatibility was observed for nurses' participation in the decision-making process.The study identified strengths and weaknesses in the "Health Promoting Workplace" Subproject implementation process. It also emphasized the importance of the adaptation of tools to local conditions. In this case, it is the WHO assessment tool for hospitals wishing to assess their health promotion practices and to stimulate their development. PMID- 27391885 TI - [Compulsory admissions in psychiatry: comparative analysis between sensitive urban zones and other areas]. AB - OBJECTIVES: To compare compulsory and non-compulsory psychiatric hospitalization rates between Sensitive Urban Zones (SUZ) and other areas. An association between Compulsory Admission at the Request of a State Representative (CARSR) and SUZ was then investigated among compulsory admission patients. METHODS: This retrospective observational study identified hospitalized patients in a French psychiatric hospital territory from 2012 to 2013. Legal methods of admission, medical and demographic data, as well as place of residence (SUZ or not) were extracted from the hospital information system. Hospitalization rate analysis was based on 2010 INSEE census data. Multivariate analysis among compulsory admission patients was performed by logistic regression. RESULTS: 2,677 patients were hospitalized from 2012 to 2013. The hospitalization rate during the two years of the study was about 6.25 patients per 1,000 inhabitants in SUZ and about 3.93 in other areas (p < 0.0001). Although a statistically significant association was observed between CARSR and SUZ among compulsory admission patients (p = 0.003), multivariate analysis did not confirm this result (OR = 1.29, 95% CI [0.90 ; 1.85], p = 0.16). Characteristics related to CARSR were male gender (OR = 3.72, 95% CI [2.56 ; 5.51], p < 0.0001), schizophrenia (OR = 1.84, 95% CI [1.28 ; 2.66], p=0.001) and personality and behavioral disorders (OR = 1.83, 95% CI [1.30 ; 2.56], p = 0.0005). CONCLUSION: Psychiatric hospitalization rates and the proportion of patients admitted at the request of a state representative were higher in SUZ than in other areas, but this association was not confirmed by multivariate analysis. PMID- 27391886 TI - [Psychiatric features in the elderly with or without dementia in a geriatric hospital]. AB - OBJECTIVES: The growing number of elderly people is challenging the reorganization of European health care systems. In France, there is an overlap between geriatric and psychiatric care of the elderly. This study was designed to describe the features of these patients, managed in both geriatric and geriatric psychiatry inpatient units. METHODS: We used The Programme Medicalise de Systeme d'Information for the period 2009-2014. We focused on psychiatric disorders and dementia. RESULTS: 11.17% and 25% of patients have psychiatric disorders without dementia in geriatric and geriatric psychiatry units, respectively. Depression is the main mental illness. Their characteristics do not differ from those observed in other patients, apart from age. CONCLUSION: A part of the elderly psychiatric population is managed in the geriatric care system. Our results underline the importance of more integrated care between geriatric and psychiatry to prevent exclusion of patients from the health care system. Depression in elderly without dementia could justify the creation of specific inpatient units. PMID- 27391887 TI - [Digital data and disease management]. AB - INTRODUCTION: The search and exchange of digital data via Networks or Internet, especially the web, have become more widely available over recent years. Patients can now find information about their problems. OBJECTIVES: Determine the impact of this information in terms of seeking care. METHODS: Questionnaires were given to adults consulting their doctor. RESULTS: Health Information on the Internet was searched by 69% of patients which prompted 57% of them to consult. Some of them asked for medical imaging, blood tests or another medical advice. Self medication was reported by 12% of patients, 15% requested a drug from the pharmacist or doctor, and 11% stopped using or requested a change of the drug. DISCUSSION: Access to digital data by patients impacts their access to care at various stages. Knowledge leads to changes in behaviour that resulted in modification of access to care ... The use of the Internet and the digital data are by patients is a source of learning about the disease itself and also about its management in their interactions with caregivers. CONCLUSION: These skills could be used by caregivers to empower the patient's autonomy. PMID- 27391888 TI - [Oral hygiene prevention actions at Albert Chenevier hospital: Open day for schools]. AB - BACKGROUND: Since 1994, the dental department of Albert Chenevier hospital in Creteil organizes an "open day" for schoolchildren in Creteil. This action is organized in collaboration with the Creteil Social Action Community Centre (CCAS) health prevention service and is part of a prevention programme designed to reduce caries prevalence in children aged 6 to 7 years. This programme helps especially children from disadvantaged groups or with disabilities. We want to report results for the last three years. METHODS: Allezard and Beauvin schools and La Nichee and Leloup special schools attended this open day, consisted of two parts. The first part concerned prevention, designed to teach children to brush their teeth. The second part consisted of screening of tooth decay. CCAS provided disposable toothbrushes, toothpaste and examination instruments. The Albert Chenevier hospital dental department provided hospital personnel, appropriate hygiene materials and premises. RESULTS: About 50% of children of all ages and from all schools presented tooth decay. The use of dental care decreased between 2011 and 2013 for Allezard and Beauvin schools. It was 100% in 2011 and 2012 for special schools and virtually zero for the Beauvin special school for disabled children. Dental care decreased from year to year for these special classes and for special schools. About 20% of children at the Allezard school had good oral hygiene. CONCLUSION: The effect of health education activities can be improved by involving the child's family. Oral hygiene must be based on a collective approach in which everyone has a role to play: children, parents, educators, teachers, principals and nursing staff should be involved to ensure continuing improvement of oral hygiene and to try to promote access to care. This preventive action therefore remains necessary and the information must be repeated. PMID- 27391889 TI - [Sesame Health Programme at Senegal: Limitations of this free healthcare model]. AB - INTRODUCTION: Up until now, elderly people have experienced medical management difficulties despite the free care provided by the Sesame Health Programme. The objective of this study was to determine the costs borne by beneficiaries and/or their families and to evaluate these costs in relation to overall management. This comprehensive, cross-sectional, quantitative study was conducted from 21 February to 21 March 2011 in the Ouakam gerontology centre. METHODS: Epi Info Version 6 software was used for data analysis. The study population was composed of 203 patients with a mean age of 68 years, with 59% of women and 63% of retired subjects. The most common diseases were hypertension (52%), cataract (16%), and osteoarthritis (12%). RESULTS: The beneficiaries healthcare costs were covered by the Sesame Health Programme, apart from most of the drugs used to treat chronic diseases, which remained at the charge of patients and/or their families. The overall mean cost of monthly management of the diseases detected in elderly people was estimated to be CFA 37,700, a large share of which (65%) was supported by the patient and/or the family corresponding to the purchase of these drugs. Other dysfunctions were also observed, particularly the difficulty of targeting beneficiaries, generic stock shortages, absence of generics for the treatment of chronic diseases. CONCLUSION: Recommendations are formulated to improve implementation of the Sesame Health Programme. PMID- 27391890 TI - [Patient's role and chronic disease in Mali: between policies and expert and lay practices]. AB - INTRODUCTION: The growing burden of non-communicable diseases challenges health systems of low-and middle-income countries and requires health care reform by the introduction of models focused on patient participation. OBJECTIVE: This article puts into perspective the management of two chronic diseases, diabetes and HIV/AIDS, in Mali. It explores the way in which the patient's role is conceived and implemented at three levels: policy-makers, healthcare professionals and patients, in order to more clearly understand the dynamics and rationales underlying promotion of the patient's role in the context of a low-income country. METHODS: Results were derived from qualitative interviews conducted between 2010 and 2012 with key stakeholders involved in policy, healthcare professionals and patients, and from observations of healthcare relationships in two specialized healthcare structures in Bamako. RESULTS: The chronic nature of the disease is not sufficient to define the patient's role in healthcare. Other factors also influence the emergence and practice of an active patient care model: the political, clinical and social history of the disease; the institutional work contexts of healthcare professionals; patients' representations and practices. Patients are well aware of the role they need to play in the management of a chronic disease and they develop resources to remain active. CONCLUSIONS: These various dynamics should be better taken into account to make effective changes in the health care system and to strengthen patients' autonomy. PMID- 27391891 TI - [Preparation of healthcare workers against the threat of Ebola virus disease in Ivory Coast]. AB - INTRODUCTION: Since the declaration of the Ebola virus disease outbreak in West Africa, the government of Ivory Coast has organized the training of medical staff in all health regions of the country. This study was conducted one month after this training in order to assess the knowledge, attitudes and practices of health workers concerning Ebola virus disease in an Ivory Coast health region their preparation in relation to this disease. METHODS: In May-June 2014, we conducted a descriptive cross-sectional study of 176 health workers from private and public health facilities in 5 health districts. RESULTS: Among the respondents, 15.5% attended the training on Ebola disease organized by the Ministry of Health. They knew that the disease is transmitted from animals to humans by body fluids (85.6%), and from human to human by body fluids of a sick person or a cadavre (82.8%). 96% said they were at risk of contracting the disease. DISCUSSION: In view of the persistent threat of the disease, ignorance of certain aspects of the disease could be a weakness in the prevention of nosocomial transmission of the disease. Knowledge of the disease should lead to adoption of prevention measures. However, routine use of protection equipment, including gloves, depends on its availability. CONCLUSION: The lack of infection prevention and control equipment could be a weak point in preparation of the response to an Ebola disease outbreak. PMID- 27391892 TI - [Ebola, a matter of trust]. AB - An outbreak of Ebola occurred in 2014-2015 in Guinea, Liberia and Sierra Leone. Two opposing hypotheses may be put forward to explain its decline in these countries. The first of which attributes this decline to authoritarian emergency action imposed on the populations. This comprised the opening of specialized centres to fight the epidemic, directing people suspected of being contaminated to travel to such centres, and taking charge of cremating the remains of the deceased victims of Ebola. This process was founded on the supposed weaknesses of the health systems in question and sought to offer a substitute for them. The second hypothesis suggests that the reduction of the number of Ebola cases in West Africa was due to the combined efforts of civil society and the local health services facing up to this new challenge. This explanation is based on the experience of the Democratic Republic of the Congo which has confronted seven epidemics of Ebola since 1976 and which privileged the mobilization of local capacities involving both the health services and the community. This last hypothesis is built on the appreciation of local strengths and strives to mobilize and facilitate such assets. What was the impact of such radically different approaches to managing the outbreak? PMID- 27391893 TI - [Not Available]. PMID- 27391894 TI - The Synthesis of L-Alanyl and beta-Alanyl Derivatives of 2-Aminoacridone and Their Application in the Detection of Clinically-Important Microorganisms. AB - In clinical microbiology the speed with which pathogenic microorganisms may be detected has a direct impact on patient health. One important strategy used in the laboratory is the growth of cultures in the presence of an enzymatic substrate which, once transformed by the appropriate microbial enzyme, generates a detectable colour or fluorescence output. Such substrates have previously been prepared by our group and others and are available as commercial diagnostic kits, however they all suffer from some degree of diffusion when used in a solid growth medium. This diffusion complicates the detection and differentiation of species in polymicrobial cultures and so we sought to improve on our previous work. In this work we have prepared and evaluated a series of novel fluorogenic enzyme substrates based on N-substituted-2-aminoacridones. All of the prepared substrates were found to be suitable for the detection and differentiation of certain microorganisms, however those based on the 2-amino-10-benzylacridone core in particular showed no apparent diffusion when incorporated into solid growth media. On transformation these substrates generated brightly fluorescent colonies that are clearly contrasted with the background medium due to the difference in emission wavelength (lambdaem 445-450 nm for the substrate, lambdaem 550 nm for the product). Here we have shown that our L-alanyl aminopeptidase substrate, 2-(N L-alanylamino)-10-benzylacridone, is particularly suited to the detection of Gram negative bacteria, and our beta-alanyl aminopeptidase substrate, 2-(N- beta alanylamino)-10-benzylacridone, to the detection of Pseudomonas aeruginosa and Serratia marcescens when grown on solid media incorporating these substrates. The resulting fluorophore shows no apparent diffusion from the colonies of interest, and the enhanced sensitivity offered by fluorescent emission may allow for the detection of these organisms as microcolonies using automated fluorescence microscopy. PMID- 27391895 TI - A Comparison of Biocompatibility of a Titanium Alloy Fabricated by Electron Beam Melting and Selective Laser Melting. AB - Electron beam melting (EBM) and selective laser melting (SLM) are two advanced rapid prototyping manufacturing technologies capable of fabricating complex structures and geometric shapes from metallic materials using computer tomography (CT) and Computer-aided Design (CAD) data. Compared to traditional technologies used for metallic products, EBM and SLM alter the mechanical, physical and chemical properties, which are closely related to the biocompatibility of metallic products. In this study, we evaluate and compare the biocompatibility, including cytocompatibility, haemocompatibility, skin irritation and skin sensitivity of Ti6Al4V fabricated by EBM and SLM. The results were analysed using one-way ANOVA and Tukey's multiple comparison test. Both the EBM and SLM Ti6Al4V exhibited good cytobiocompatibility. The haemolytic ratios of the SLM and EBM were 2.24% and 2.46%, respectively, which demonstrated good haemocompatibility. The EBM and SLM Ti6Al4V samples showed no dermal irritation when exposed to rabbits. In a delayed hypersensitivity test, no skin allergic reaction from the EBM or the SLM Ti6Al4V was observed in guinea pigs. Based on these results, Ti6Al4V fabricated by EBM and SLM were good cytobiocompatible, haemocompatible, non-irritant and non-sensitizing materials. Although the data for cell adhesion, proliferation, ALP activity and the haemolytic ratio was higher for the SLM group, there were no significant differences between the different manufacturing methods. PMID- 27391896 TI - Patterns and causes of liver involvement in acute dengue infection. AB - BACKGROUND: Liver involvement in acute dengue infection is frequently observed and sometimes leads to acute liver failure, with fatal outcomes. Many factors are thought to contribute to liver dysfunction, including hypoxic injury due to decreased perfusion, direct damage by the virus and immune mediated injury. In this study, we sought to identify the pattern in the change in liver enzymes throughout the illness and its association with the degree of viraemia, onset and extent of plasma leakage and inflammatory mediators. METHODS: Serial daily blood samples were obtained from 55 adult patients with acute dengue from the time of admission to discharge and the liver function tests, viral loads and cytokines were assessed. The onset and extent of fluid leakage was measured by daily ultrasound examinations and all clinical and laboratory features were serially recorded. RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT) and gamma glutamyl transferase (GGT) levels were elevated in patients with dengue infection throughout the illness. The highest AST levels were seen on day 6 of illness and both AST and GGT levels were significantly higher in patients with severe dengue (SD), when compared to those with non-severe dengue (NSD) on day 5 and 6 of illness. Three patients with SD had AST and ALT values of >1000/IU in the absence of any fluid leakage or a rise in the haematocrit (>=20 %). The peak of the AST levels and the lowest serum albumin levels were seen 24 h before the maximum fluid leakage and 24 h after the peak in viraemia. Both serum IL-10 and IL-17 levels were elevated during early illness and were significantly higher in those with SD when compared to NSD. CONCLUSION: Dengue associated liver injury appears to peak around day 6 and 7. Therefore, liver function tests done at earlier dates might not reflect the extent of liver involvement in acute infection. Since severe liver involvement can occur in the absence of fluid leakage, after the peak viraemia, and since it is associated with high IL-17 and IL-10 levels, possible immune mechanisms leading to hepatic damage should be investigated. PMID- 27391897 TI - Anion Exchanger 2 Regulates Dectin-1-Dependent Phagocytosis and Killing of Candida albicans. AB - Anion exchanger 2 (Ae2; gene symbol, Slc4a2) is a plasma membrane Cl-/HCO3- exchanger expressed in the gastrointestinal tract, kidney and bone. We have previously shown that Ae2 is required for the function of osteoclasts, bone resorbing cells of the macrophage lineage, to maintain homeostatic cytoplasmic pH and electroneutrality during acid secretion. Macrophages require endosomal acidification for pathogen killing during the process known as phagocytosis. Chloride is thought to be the principal ion responsible for maintaining electroneutrality during organelle acidification, but whether Cl-/HCO3- exchangers such as Ae2 contribute to macrophage function is not known. In this study we investigated the role of Ae2 in primary macrophages during phagocytosis. We find that Ae2 is expressed in macrophages where it regulates intracellular pH and the binding of Zymosan, a fungal cell wall derivative. Surprisingly, the transcription and surface expression of Dectin-1, the major phagocytic receptor for Candida albicans (C. albicans) and Zymosan, is reduced in the absence of Ae2. As a consequence, Zymosan-induced Tnfalpha expression is also impaired in Ae2 deficient macrophages. Similar to Ae2 deficiency, pharmacological alkalinization of lysosomal pH with bafilomycin A decreases both Dectin-1 mRNA and cell surface expression. Finally, Ae2-deficient macrophages demonstrate defective phagocytosis and killing of the human pathogenic fungus C. albicans. Our results strongly suggest that Ae2 is a critical factor in the innate response to C. albicans. This study represents an important contribution to a better understanding of how Dectin-1 expression and fungal clearance is regulated. PMID- 27391898 TI - Evaluation of an Automated System for Reading and Interpreting Disk Diffusion Antimicrobial Susceptibility Testing of Fastidious Bacteria. AB - Results of disk diffusion antimicrobial susceptibility testing depend on individual visual reading of inhibition zone diameters. Therefore, automated reading using camera systems might represent a useful tool for standardization. In this study, the ADAGIO automated system (Bio-Rad) was evaluated for reading disk diffusion tests of fastidious bacteria. 144 clinical isolates (68 beta haemolytic streptococci, 28 Streptococcus pneumoniae, 18 viridans group streptococci, 13 Haemophilus influenzae, 7 Moraxella catarrhalis, and 10 Campylobacter jejuni) were tested on Mueller-Hinton agar supplemented with 5% defibrinated horse blood and 20 mg/L beta-NAD (MH-F, Oxoid) according to EUCAST. Plates were read manually with a ruler and automatically using the ADAGIO system. Inhibition zone diameters, indicated by the automated system, were visually controlled and adjusted, if necessary. Among 1548 isolate-antibiotic combinations, comparison of automated vs. manual reading yielded categorical agreement (CA) without visual adjustment of the automatically determined zone diameters in 81.4%. In 20% (309 of 1548) of tests it was deemed necessary to adjust the automatically determined zone diameter after visual control. After adjustment, CA was 94.8%; very major errors (false susceptible interpretation), major errors (false resistant interpretation) and minor errors (false categorization involving intermediate result), calculated according to the ISO 20776-2 guideline, accounted to 13.7% (13 of 95 resistant results), 3.3% (47 of 1424 susceptible results) and 1.4% (21 of 1548 total results), respectively, compared to manual reading. The ADAGIO system allowed for automated reading of disk diffusion testing in fastidious bacteria and, after visual validation of the automated results, yielded good categorical agreement with manual reading. PMID- 27391899 TI - Roles of Arbuscular Mycorrhizal Fungi and Soil Abiotic Conditions in the Establishment of a Dry Grassland Community. AB - BACKGROUND: The importance of soil biota in the composition of mature plant communities is commonly acknowledged. In contrast, the role of soil biota in the early establishment of new plant communities and their relative importance for soil abiotic conditions are still poorly understood. AIMS AND METHODS: The aim of this study was to understand the effects of soil origin and soil fungal communities on the composition of a newly established dry grassland plant community. We used soil from two different origins (dry grassland and abandoned field) with different pH and nutrient and mineral content. Grassland microcosms were established by sowing seeds of 54 species of dry grassland plants into the studied soils. To suppress soil fungi, half of the pots were regularly treated with fungicide. In this way, we studied the independent and combined effects of soil origin and soil community on the establishment of dry grassland communities. KEY RESULTS: The effect of suppressing the soil fungal community on the richness and composition of the plant communities was much stronger than the effect of soil origin. Contrary to our expectations, the effects of these two factors were largely additive, indicating the same degree of importance of soil fungal communities in the establishment of species-rich plant communities in the soils from both origins. The negative effect of suppressing soil fungi on species richness, however, occurred later in the soil from the abandoned field than in the soil from the grassland. This result likely occurred because the negative effects of the suppression of fungi in the field soil were caused mainly by changes in plant community composition and increased competition. In contrast, in the grassland soil, the absence of soil fungi was limiting for plants already at the early stages of their establishment, i.e., in the phases of germination and early recruitment. While fungicide affects not only arbuscular mycorrhizal fungi but also other biota, our data indicate that changes in the AMF communities are the most likely drivers of the observed changes. The effects of other soil biota, however, cannot be fully excluded. CONCLUSIONS: These results suggest that the availability of soil fungi may not be the most important limiting factor for the establishment of grassland species in abandoned fields if we manage to reduce the intensity of competition at these sites e.g., by mowing or grazing. PMID- 27391900 TI - Six months versus nine months anti-tuberculous therapy for female genital tuberculosis: a randomized controlled trial. AB - OBJECTIVE: To compare six months versus nine months anti-tuberculous therapy in patients of female genital tuberculosis. STUDY DESIGN: It was a randomized controlled trial in a tertiary referral center teaching institute on 175 women presenting with infertility and found to have female genital tuberculosis on clinical examination and investigations. Group I women (86 women) were given 9 months of intermitted anti-tuberculous therapy under directly observed treatment short course (DOTS) strategy while Group II (89 women) were given 6 months of anti-tuberculous therapy under DOTS. Patients were evaluated for primary end points (complete cure, partial response, no response) and secondary end points (recurrence rate, pregnancy rate) during treatment. All patients were followed up further for one year after completion of therapy to assess recurrence of disease and further pregnancies. RESULTS: Baseline characteristics were similar between two randomized groups. There was no difference in the complete clinical response rate (95.3% vs 97.7%, p=0.441) between 9-months and 6-months groups. Four patients in 9-months group and two patients in 6-months group had recurrence of disease and required category II anti tuberculous therapy (p=0.441). Pregnancy rate during treatment and up to one year follow up was also similar in the two groups (23.2% vs 21.3%, p=0.762). Side effects occurred in 27(31.4%) and 29(32.6%) in 9-months and 6-months of therapy and were similar (p=0.866). CONCLUSIONS: There was no difference in complete cure rate, recurrent rate and pregnancy rate for either 6-months or 9-months of intermittent directly observed treatment short course anti-tuberculous therapy in female genital tuberculosis. CLINICAL TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov with registration no: CTRI/2009/091/001088. PMID- 27391901 TI - Combined first-trimester Down syndrome screening in HIV-infected women. AB - OBJECTIVE: To determine if human immunodeficiency virus (HIV) infection or antiretroviral therapy interferes with maternal levels of free human beta chorionic gonadotrophin (hCGbeta) and pregnancy-associated plasma protein-A (PAPP A) and whether any such influence alters first-trimester Down syndrome (DS) screening in HIV-infected women. STUDY DESIGN: We performed a multicenter 1:2 matched case-control study comparing 84 HIV-infected women with singleton pregnancies with controls randomly selected among uninfected women, delivered and screened in the same center and matched for maternal age, geographical origin and fetal sex. RESULTS: Groups did not differ significantly in screening results, although case women showed a slightly lower median free hCGbeta multiple of the median (MoM) (1.11 versus 1.24 MoM, p=0.32) and higher median PAPP-A MoM (1.45 versus 1.32 MoM, p=0.23) than control women. The false-positive rate was similar in the case and control groups (5% versus 6.5%, p=0.5). Biomarker levels did not differ when comparing treated and untreated patients with their respective controls, and with one another. CONCLUSION: First-trimester DS combined screening biomarker levels and calculated risk do not seem to be significantly altered by HIV infection or antiretroviral treatment. This screening strategy appears to be suitable for HIV-infected women. PMID- 27391902 TI - The Effects of High Level Magnesium Dialysis/Substitution Fluid on Magnesium Homeostasis under Regional Citrate Anticoagulation in Critically Ill. AB - BACKGROUND: The requirements for magnesium (Mg) supplementation increase under regional citrate anticoagulation (RCA) because citrate acts by chelation of bivalent cations within the blood circuit. The level of magnesium in commercially available fluids for continuous renal replacement therapy (CRRT) may not be sufficient to prevent hypomagnesemia. METHODS: Patients (n = 45) on CRRT (2,000 ml/h, blood flow (Qb) 100 ml/min) with RCA modality (4% trisodium citrate) using calcium free fluid with 0.75 mmol/l of Mg with additional magnesium substitution were observed after switch to the calcium-free fluid with magnesium concentration of 1.50 mmol/l (n = 42) and no extra magnesium replenishment. All patients had renal indications for CRRT, were treated with the same devices, filters and the same postfilter ionized calcium endpoint (<0.4 mmol/l) of prefilter citrate dosage. Under the high level Mg fluid the Qb, dosages of citrate and CRRT were consequently escalated in 9h steps to test various settings. RESULTS: Median balance of Mg was -0.91 (-1.18 to -0.53) mmol/h with Mg 0.75 mmol/l and 0.2 (0.06 0.35) mmol/h when fluid with Mg 1.50 mmol/l was used. It was close to zero (0.02 (-0.12-0.18) mmol/h) with higher blood flow and dosage of citrate, increased again to 0.15 (-0.11-0.25) mmol/h with 3,000 ml/h of high magnesium containing fluid (p<0.001). The arterial levels of Mg were mildly increased after the change for high level magnesium containing fluid (p<0.01). CONCLUSIONS: Compared to ordinary dialysis fluid the mildly hypermagnesemic fluid provided even balances and adequate levels within ordinary configurations of CRRT with RCA and without a need for extra magnesium replenishment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01361581. PMID- 27391903 TI - Retinal toxicity induced by antimalarial drugs: literature review and case report. AB - Antimalarial drugs are widely used in several countries for control of rheumatologic diseases such as systemic lupus erythematosus and rheumatoid arthritis. They are still used in Mexico because of their low cost and few secondary effects, most of which are mild and reversible. Even so, at an ophthalmological level, they could produce irreversible visual damage, which is why it is important to have ophthalmological evaluation and proper follow up. We present a clinical case as an example of characteristic ophthalmological findings as well as risk factors for retinal toxicity. We then discuss guidelines for diagnosis and follow up of patients who use antimalarial drugs for the treatment of rheumatologic illnesses. PMID- 27391906 TI - Remote C-H Functionalization by a Palladium-Catalyzed Transannular Approach. AB - Now within reach: In the remote C-H arylation of alicyclic amines the key step is the transannular coordination of the palladium catalyst (see picture, DG=directing group). This strategy is convenient for the late-stage functionalization of complex bioactive molecules in order to probe structure activity relationships. PMID- 27391904 TI - Algorithms for differential splicing detection using exon arrays: a comparative assessment. AB - BACKGROUND: The analysis of differential splicing (DS) is crucial for understanding physiological processes in cells and organs. In particular, aberrant transcripts are known to be involved in various diseases including cancer. A widely used technique for studying DS are exon arrays. Over the last decade a variety of algorithms for the detection of DS events from exon arrays has been developed. However, no comprehensive, comparative evaluation including sensitivity to the most important data features has been conducted so far. To this end, we created multiple data sets based on simulated data to assess strengths and weaknesses of seven published methods as well as a newly developed method, KLAS. Additionally, we evaluated all methods on two cancer data sets that comprised RT-PCR validated results. RESULTS: Our studies indicated ARH as the most robust methods when integrating the results over all scenarios and data sets. Nevertheless, special cases or requirements favor other methods. While FIRMA was highly sensitive according to experimental data, SplicingCompass, MIDAS and ANOSVA showed high specificity throughout the scenarios. On experimental data ARH, FIRMA, MIDAS, and KLAS performed best. CONCLUSIONS: Each method shows different characteristics regarding sensitivity, specificity, interference to certain data settings and robustness over multiple data sets. While some methods can be considered as generally good choices over all data sets and scenarios, other methods show heterogeneous prediction quality on the different data sets. The adequate method has to be chosen carefully and with a defined study aim in mind. PMID- 27391908 TI - Lasiodiplodia species fungal osteomyelitis in a multiple myeloma patient. AB - Lasiodiplodia species are environmental fungi that have been reported as a cause of infection in both immunocompetent and immunocompromised patients. We present a case of fungal osteomyelitis caused by Lasiodiplodia species in a patient with multiple myeloma after autologous stem cell transplant. The patient was successfully treated with a combination of surgery and oral voriconzole. To the best of our knowledge, this is the first reported case of fungal osteomyelitis caused by Lasiodiplodia species. PMID- 27391909 TI - Evaluation of a Single Intra-Articular Injection of Autologous Protein Solution for Treatment of Osteoarthritis in a Canine Population. AB - OBJECTIVE: To evaluate the safety and efficacy of an intra-articular injection of autologous protein solution (APS) for treatment of canine osteoarthritis (OA). STUDY DESIGN: Prospective, randomized, blinded, placebo-controlled pilot clinical trial. ANIMALS: Client-owned dogs with single limb lameness because of OA in a stifle or elbow joint (n=21). METHODS: Lame dogs, confirmed with OA by physical and lameness examination and imaging, were randomly assigned to control or treatment groups. Owners, blinded to treatment, scored pain (University of Pennsylvania Canine Brief Pain Inventory) and lameness severity (Hudson Visual Analogue Scale [HVAS]). Weight-bearing was assessed by kinetic gait analysis. Dogs were injected intra-articularly with APS (treatment group) or saline solution (control group). Evaluations were performed before injection, and 2 and 12 weeks post-injection. RESULTS: Compared to pretreatment values, APS treatment data showed a significant improvement in week 12 pain scores (improved 25.6% over baseline), lameness scores (improved 15% over baseline) and peak vertical force (PVF; N/kg; increased 14.9% of baseline), as well as vertical impulse (Ns/kg) and PVF normalized to stance time (N/kg/s). Control group dogs improved at week 2 in owner assigned indices, but not force plate values and had no significant improvement in scores or force plate values from pretreatment values at 12 weeks. CONCLUSION: APS injection reduced pain and lameness scores and increased weight bearing associated with the OA-affected joint in dogs at 12 weeks providing preliminary evidence that APS therapy may be beneficial in the treatment of OA in dogs and supporting pursuit of additional studies. PMID- 27391907 TI - Impact of telomere length on the outcome of allogeneic stem cell transplantation for poor-risk chronic lymphocytic leukaemia: results from the GCLLSG CLL3X trial. PMID- 27391910 TI - Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers. AB - BACKGROUND: Bisoprolol is one of the most widely used beta-blockers characterised by cardioselectivity, and it has no intrinsic sympathomimetic activity. It is commonly used in the treatment of coronary heart disease and heart failure. AIM: The aim of study was to assess the bioequivalence of the film-coated tablets containing 2.5 mg of bisoprolol (Bisocard(r) - the medicinal product) to the original medicinal product (Concor Cor 2.5(r) - the reference). METHODS: A randomised, open-label, two-period, crossover, single-dose, relative bioavailability study was conducted in fasted healthy Caucasian volunteers. A single 10-mg oral dose (four tablets of 2.5 mg) of the test or reference product was followed by a 14-day wash-out period, after which the subjects received the alternative product. Blood was sampled within a period of 60 h post administration in pre-specified time points. Bisoprolol concentrations were determined by a validated LC-MS/MS method. The products were considered bioequivalent if the 90% confidence interval (CI) of the log-transformed geometric mean ratios (test vs. reference) for AUC(0-t), AUC(0-infinity), and Cmax were within 80-125% limits. Adverse events were monitored during the study based on the subject claims and clinical parameters. RESULTS: Twenty-six healthy male and female volunteers (mean age ca. 29 years; body mass index 22.7 kg/m2) were in-cluded in the study, and 24 completed the clinical part. The geometric mean ratios (test/reference) for the log-transformed AUC(0-t), AUC(0-infinity), and Cmax were 95.16% (90% CI 92.52-97.87%), 95.08% (90% CI 92.40-97.83%), and 100.00% (90% CI 94.83-105.45%), respectively. There were no significant differences in the pharmacokinetic parameters between the test and reference formulations. No serious adverse events were reported. CONCLUSIONS: The results of this single-dose study in healthy Caucasian volunteers indicate that Bisocard(r); 2.5 mg film-coated tablets are bioequivalent to the reference product - Concor Cor 2.5(r); 2.5 mg film-coated tablets. Both products had similar safety profile and have been well tolerated. PMID- 27391911 TI - Does the use of a chest compression system in children improve the effectiveness of chest compressions? A randomised crossover simulation pilot study. AB - BACKGROUND: Providing high-quality chest compressions is a key element affecting the effectiveness of cardiopulmonary resuscitation (CPR). AIM: To evaluate the effectiveness of standard (manual) chest compressions (Standard BLS, standard basic life support) and those performed with the use of the Lifeline ARM chest compression system (ARM; Defibtech). METHODS: The study was designed as a randomised crossover study. In total, 37 nurses participated in the study. They performed a randomized 2-min asynchronous resuscitation using the Standard BLS method or the ARM system. The following parameters were measured: the total number of chest compressions, the frequency of compressions (min-1), compression depth (mm), and the percentage of correctly performed chest compressions and total chest decompressions. The authors also analysed the participants' preferences concerning the use of particular CPR techniques in the clinical setting. RESULTS: The results obtained during the simulation study with the application of the ARM system were statistically significantly better than those with the Standard BLS method (p < 0.05) in the case of all analysed parameters. CONCLUSIONS: During the simulated child resuscitation performed by the nurses, the application of the Lifeline ARM chest compression system significantly improved the effectiveness of chest compressions. PMID- 27391912 TI - The relation between vitamin B12 and SYNTAX score. AB - BACKGROUND: Vitamin B12 is required in the metabolism of homocysteine. Vitamin B12 deficiency has been implicated in endothelial dysfunction and cardiovascular disease via hyperhomocysteinaemia. However, the association of vitamin B12 and the severity of coronary artery disease has not been studied to date. AIM: This study was conducted with the aim of evaluating the relationship between vitamin B12 and SYNTAX score. METHODS: Medical records of consecutive patients who underwent coronary artery bypass grafting surgery were retrospectively reviewed. The study group consisted of 127 patients. Vitamin B12, other biochemical parameters, clinical and echocardiographic parameters, and SYNTAX score were evaluated for all patients. RESULTS: Patients with vitamin B12 deficiency had a higher prevalence of cardiovascular risk factors such as diabetes mellitus, and history of transient ischaemic attack/stroke and heart failure. The SYNTAX score was significantly higher in patients with vitamin B12 deficiency (29.2 +/- 4.9 vs. 22.5 +/- 4.5, p < 0.05). CONCLUSIONS: In our study, we found a significant relationship between vitamin B12 deficiency and SYNTAX score, demon-strating the severity and complexity of coronary artery disease. PMID- 27391913 TI - A study to evaluate the prevalence and determinants of stress coping strategies in heart failure patients in Poland (CAPS-LOCK-HF sub-study). AB - BACKGROUND AND AIM: We aimed to evaluate the prevalence and determinants of different stress coping strategies in Polish patients suffering from heart failure with reduced ejection fraction (HFREF). METHODS: This manuscript is a sub study of the CAPS-LOCK-HF multicentre psychological status assessment of patients with HFREF. Patients with > six-month history of HFREF and clinical stability for >= three months and left ventricular ejection fraction (LVEF) < 45% were enrolled in the study. Demographic and clinical variables were obtained from medical records, while a standardised Coping Inventory for Stressful Situations (CISS) was applied to all subjects. RESULTS: The study comprised 758 patients (599 men; 79%) with a median age of 64 years (IQR 58-71). Median LVEF was 33% (25-40). Subjects most commonly used task-oriented coping strategies (median CISS score 55 points; IQR 49-61), followed by avoidance (45 points; 39-50) and emotion-oriented coping strategies (41 points; 34-48). Distraction-based avoidance coping strategies (20 points; 16-23) were more pronounced than social diversion strategies (16 points; 14-19). Multiple regression analysis showed that higher New York Heart Association (NYHA) class and lower systolic blood pressure were independent predictors of task-oriented style. Emotion-oriented coping was more common among females and higher NYHA classes, and in patients who did not take angiotensin-converting enzyme inhibitors. Patients who used avoidance-oriented strategies were more frequently those in sinus rhythm on assessment and those who had less history of neoplastic disease. CONCLUSIONS: Patients with HFREF most commonly use favourable task-oriented coping strategies. However, female patients and those with higher NYHA classes tend to use potentially detrimental emotion oriented coping strategies. PMID- 27391915 TI - Erratum. PMID- 27391914 TI - Vitamin D insufficiency is associated with coronary artery tortuosity. AB - BACKGROUND: Increasing evidence suggests a relationship between vitamin D (VD) insufficiency and cardiovascular disease. AIM: We aimed to investigate the association between serum 25-hydroxyvitamin D (25-OH VD) with coronary tortuosity (CT) in patients with normal or near-normal (< 40% stenosis) coronary arteries. METHODS: The present study was cross-sectional and observational. We enrolled 356 consecutive patients who had undergone coronary angiography for suspected ischaemic heart disease and were found to have normal or near-normal coronary arteries. Patients were categorised as VD insufficient (< 30 ng/mL) or VD sufficient (>= 30 ng/dL). CT was defined as the presence of >= three bends (defined as >= 45 degrees change in vessel direction) along the main trunk of at least one coronary artery, present both in systole and in diastole. RESULTS: The study populations were divided into two groups according to the presence of CT: patients with CT (n = 103, 29%) and patients without CT (NCT; n = 253, 71%). CT is more frequently seen in elderly women and is positively correlated with hypertension. The incidence of VD insufficiency was significantly higher in the CT group (n = 46, 45%) than in the NCT group (n = 90, 36%; p = 0.005). In further multivariate logistic regression analyses, adjustment for major clinical parameters affecting CT showed statistically significant correlations between 25 OH VD and CT (odds ratio = 0.77, 95% confidence interval 0.66-0.98, p = 0.006). CONCLUSIONS: Vitamin D insufficiency was independently associated with coronary tortuosity. PMID- 27391916 TI - EOV Editorial board page. PMID- 27391917 TI - Association of self-reported sleep duration and hypertension: Results of a Chinese prospective cohort study. AB - OBJECTIVES: To examine the association of self-reported sleep duration and hypertension using the data from Tianjin China. METHODS: Participants aged 40-70 years without hypertension were recruited with a stratified cluster sampling method across six districts of Tianjin, China. Information regarding their sociodemographic and lifestyle-related characteristics was gathered by questionnaires. After 2 years of follow-up, the second physical examination was taken on the same crowd. RESULTS: During the 2-year period, 874 subjects (221 men, 653 women) were successfully contacted. Multivariate logistic regression was used to analyze the relationship between the frequency of incident hypertension after the 2-year follow-up and sleep duration according to age groups. Among the younger age group (40-<55 years), a short sleep duration (<=ear h) was associated with a significantly higher risk of hypertension compared with sleeping for 7-8 h in unadjusted analyses (OR: 3.15 [95% CI: 1.04-9.54]). In a model after adjustment for the impact factors, a significant difference was also found in the frequency of incident hypertension. CONCLUSIONS: In our study, a short sleep duration (<=sho h) is a significant risk factor for hypertension in younger subjects, with no association among older subjects. PMID- 27391918 TI - Binding of Sulfonamide Antibiotics to CTABr Micelles Characterized Using (1)H NMR Spectroscopy. AB - Interactions of nine sulfonamide antibiotics (sulfadoxine, sulfathiazole, sulfamethoxazole, sulfamerazine, sulfadiazine, sulfamethazine, sulfacetamide, sulfaguanidine, and sulfanilamide) with cetyltrimethylamonium bromide (CTABr) micelles were examined using (1)H NMR spectroscopy. Seven of the nine provided a significant change in the (1)H NMR chemical shift such that the magnitude and direction (upfield vs downfield) of the chemical shift could be used to propose a locus and orientation of the sulfonamide within the micelle structure. The magnitude of the chemical shift was used to estimate the binding constant for seven sulfonamides with CTABr micelles, providing values and an overall pattern consistent with previous studies of these sulfonamides. PMID- 27391919 TI - Use of a contoured bioresorbable plate with a hemostatic plug to control life threatening bleeding from the superior sagittal sinus during hemispherotomy: technical note. AB - Profuse bleeding originating from an injured cerebral sinus can be a harrowing experience for any surgeon, particularly during an operation on a young child. Common surgical remedies include sinus ligation, primary repair, placement of a hemostatic plug, and patch or venous grafting that may require temporary stenting. In this paper the authors describe the use of a contoured bioresorbable plate to hold a hemostatic plug in place along a tear in the inferomedial portion of a relatively inaccessible part of the posterior segment of the superior sagittal sinus in an 11-kg infant undergoing hemispherotomy for epilepsy. This variation on previously described hemostatic techniques proved to be easy, effective, and ultimately lifesaving. Surgeons may find this technique useful in similar dire circumstances when previously described techniques are ineffective or impractical. PMID- 27391920 TI - Can Wnt5a and Wnt non-canonical pathways really mediate adipocyte de differentiation in a tumour microenvironment? AB - Wnt5a has been recently reported as a possible triggering factor of adipocyte de differentiation into an adipocyte-derived fibroblast in the tumour microenvironment of pancreas cancer. The Wnt/beta-catenin pathway was described in processes involving de-differentiation and epithelial-mesenchymal transition but some Wnt family-belonging molecules exert an adipogenic role on adipocyte, while other ones, such as Wnt10b or Wnt3a, an anti-adipogenic role. Although this ability depends on the different tumoural microenvironments, it is intriguing to ascertain if some Wnt molecules, participating in the non-canonical pathway, may be targeted as fundamental factors able to trigger the desmoplastic reaction of peritumoural white adipose tissue. PMID- 27391921 TI - Risk stratification in febrile neutropenic episodes in adolescent/young adult patients with cancer. AB - BACKGROUND: Risk-stratified management of febrile neutropenia (FN) allows intensive management of high-risk cases and early discharge of low-risk cases. Most risk stratification systems predicting severe infection from admission variables have been derived from childhood or adult populations and consequently their value in adolescents/young adults (AYA) may vary. Our objective was to determine their value in this population. METHODS: Data from the 'predicting infectious complications in children with cancer' (PICNICC) individual participant data collaboration were used to evaluate six previously described risk stratification schema in the AYA population. Complete case analyses were undertaken for five 'paediatric' rules, with imputation for specific missing variables of the 'adult' rule. The predictive performance of the rules or the outcome microbiologically defined infection (sensitivity, specificity and predictive values) were compared. RESULTS: Among the 5,127 episodes of FN in 3,504 patients in the PICNICC collaboration data set, 603 episodes of FN from 478 patients in 20 studies were of patients 16-25 years old. The six rules demonstrated variable sensitivity (33-96%) and specificity (13-83%). Their overall discriminatory ability was poor (area under the receiver operator curve estimates 0.514-0.593). CONCLUSIONS: Both paediatric and adult FN risk stratification schema perform poorly in AYA with cancer. An alternative rule or clinical recognition of their limitations is required. PMID- 27391922 TI - Impact of home enteral nutrition in malnourished patients with upper gastrointestinal cancer: A multicentre randomised clinical trial. AB - BACKGROUND: Weight loss is frequent in patients with gastrointestinal (GI) cancer. Nutritional status deteriorates throughout anti-cancer treatment, mostly after major surgery, increasing complications, reducing tolerance and worsening the final prognosis. Enteral nutrition is safe and effective in malnourished patients undergoing major GI surgery. Randomised trials aimed at investigating the effects of home enteral nutrition (HEN) in post-surgical patients with GI cancer are lacking. This study compares HEN and counselling in limiting weight loss during oncologic treatment. PATIENTS AND METHODS: Patients with upper GI cancer and candidate to major surgery were included in the protocol when the nutritional risk screening (NRS 2002) score was >=3. All patients were supported with enteral nutrition through a jejunostomy after surgery and randomly assigned to continue enteral nutrition or receiving nutritional counselling after discharge. Nutritional and performance status, quality of life (QoL) and tolerance to cancer treatment have been evaluated at 2 and 6 months after discharge. RESULTS: Seventy-nine patients were randomised; 38 continued enteral nutrition at home and 41 patients received nutritional counselling only. After 2 months, patients on HEN maintained their mean body weight, while patients in the nutritional counselling group showed a weight loss of 3.6 kg. Patients supported on HEN had a higher chance to complete chemotherapy as planned (48% versus 34%). QoL was not worsened by HEN. No complications were reported. CONCLUSIONS: HEN is a simple and feasible treatment to support malnourished patients with upper GI cancer after major surgery and during chemotherapy in order to limit further weight loss. PMID- 27391923 TI - Cancer registries and randomised clinical trials in rare tumours: At the two extremes of daily clinical practice. PMID- 27391924 TI - First-Passage Processes in the Genome. AB - Many essential processes in biology share a common fundamental step-establishing physical contact between distant segments of DNA. How fast this step is accomplished sets the "speed limit" for the larger-scale processes it enables, whether the process is antibody production by the immune system or tissue differentiation in a developing embryo. This naturally leads us to ask, How long does it take for DNA segments that are strung out over millions of base pairs along the chromatin fiber to find each other in the crowded cell? This question, fundamental to biology, can be recognized as the physics problem of the first passage time, or the waiting time for the first encounter. Here, we review a number of approaches to revealing the physical principles by which cells solve, with astonishing efficiency, the first-passage problem for remote genomic interactions. PMID- 27391925 TI - Mechanisms of ATP-Dependent Chromatin Remodeling Motors. AB - Chromatin remodeling motors play essential roles in all DNA-based processes. These motors catalyze diverse outcomes ranging from sliding the smallest units of chromatin, known as nucleosomes, to completely disassembling chromatin. The broad range of actions carried out by these motors on the complex template presented by chromatin raises many stimulating mechanistic questions. Other well-studied nucleic acid motors provide examples of the depth of mechanistic understanding that is achievable from detailed biophysical studies. We use these studies as a guiding framework to discuss the current state of knowledge of chromatin remodeling mechanisms and highlight exciting open questions that would continue to benefit from biophysical analyses. PMID- 27391926 TI - Group II Intron Self-Splicing. AB - Group II introns are large, autocatalytic ribozymes that catalyze RNA splicing and retrotransposition. Splicing by group II introns plays a major role in the metabolism of plants, fungi, and yeast and contributes to genetic variation in many bacteria. Group II introns have played a major role in genome evolution, as they are likely progenitors of spliceosomal introns, retroelements, and other machinery that controls genetic variation and stability. The structure and catalytic mechanism of group II introns have recently been elucidated through a combination of genetics, chemical biology, solution biochemistry, and crystallography. These studies reveal a dynamic machine that cycles progressively through multiple conformations as it stimulates the various stages of splicing. A central active site, containing a reactive metal ion cluster, catalyzes both steps of self-splicing. These studies provide insights into RNA structure, folding, and catalysis, as they raise new questions about the behavior of RNA machines. PMID- 27391927 TI - Globular Protein Folding In Vitro and In Vivo. AB - In vitro, computational, and theoretical studies of protein folding have converged to paint a rich and complex energy landscape. This landscape is sensitively modulated by environmental conditions and subject to evolutionary pressure on protein function. Of these environments, none is more complex than the cell itself, where proteins function in the cytosol, in membranes, and in different compartments. A wide variety of kinetic and thermodynamics experiments, ranging from single-molecule studies to jump kinetics and from nuclear magnetic resonance to imaging on the microscope, have elucidated how protein energy landscapes facilitate folding and how they are subject to evolutionary constraints and environmental perturbation. Here we review some recent developments in the field and refer the reader to some original work and additional reviews that cover this broad topic in protein science. PMID- 27391928 TI - Somatostatin receptors in resected hepatocellular carcinoma: status and correlation with markers of poor prognosis. AB - AIMS: To investigate the status of somatostatin receptors (SSTRs) in resected hepatocellular carcinoma (HCC). METHODS AND RESULTS: Transcript and protein levels of SSTR2, SSTR3 and SSTR5 were investigated, with real-time polymerase chain reaction (PCR) and manual and automated immunohistochemistry (IHC), in 53 resected HCCs and paired non-tumour tissues. SSTR1, SSTR4, SSTR5TMD4 and SSTR5TMD5 were analysed with real-time PCR. SSTR3 and SSTR5 transcripts were expressed in ~25% of HCCs, but not in adjacent non-tumour tissues. SSTR1 and SSTR2 transcripts were overexpressed in 42% and 32% of HCCs, respectively. SSTR4, SSTR5TMD4 and SSTR5TMD5 were not detected. Membrane staining for SSTR2 was detected in 38% of HCCs, whereas SSTR5 protein was detectable in only 11% of HCCs. SSTR3 protein was detected in the majority of HCCs and adjacent non-tumour liver tissues, but membrane staining was <20% of that in HCCs. The results obtained with the two IHC methods were highly correlated (P < 0.0001). Statistical analyses also showed a positive correlation between SSTR2 membrane staining and cytokeratin 19 expression (P = 0.04), serum alpha-fetoprotein level (P = 0.002), and poor differentiation (P = 0.05). CONCLUSIONS: Membrane SSTR2 is detected reliably in HCCs by IHC, and is a potential therapeutic target, as it is coexpressed with markers of poor prognosis. PMID- 27391929 TI - Reply to comparative effectiveness of stereotactic radiosurgery versus whole brain radiation therapy for patients with brain metastases from breast or non small cell lung cancer. PMID- 27391930 TI - SNAP-Tag Technology: A Useful Tool To Determine Affinity Constants and Other Functional Parameters of Novel Antibody Fragments. AB - Antibody derivatives, such as the single chain fragment variable (scFv), can be developed as diagnostic and therapeutic tools in cancer research, especially in the form of fusion proteins. Such derivatives are easier to produce and modify than monoclonal antibodies (mAbs) and achieve better tissue/tumor penetration. The genetic modification of scFvs is also much more straightforward than the challenging chemical modification of mAbs. Therefore, we constructed two scFvs derived from the approved monoclonal antibodies cetuximab (scFv2112) and panitumumab (scFv1711), both of which are specific for the epidermal growth factor receptor (EGFR), a well-characterized solid tumor antigen. Both scFvs were genetically fused to the SNAP-tag, an engineered version of the human DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase that allows the covalent coupling of benzylguanine (BG)-modified substrates such as fluorescent dyes. The SNAP-tag achieves controllable and irreversible protein modification and is an important tool for experimental studies in vitro and in vivo. The affinity constant of a scFv is a key functional parameter, especially in the context of a fusion protein. Therefore, we developed a method to define the affinity constants of scFv-SNAP fusion proteins by surface plasmon resonance (SPR) spectroscopy. We could confirm that both scFvs retained their functionality after fusion to the SNAP-tag in a variety of procedures and assays, including ELISA, flow cytometry, and confocal microscopy. The experimental procedures described herein, and the new protocol for affinity determination by SPR spectroscopy, are suitable for the preclinical evaluation of diverse antibody formats and derivatives. PMID- 27391931 TI - Automating Recession Curve Displacement Recharge Estimation. AB - Recharge estimation is an important and challenging element of groundwater management and resource sustainability. Many recharge estimation methods have been developed with varying data requirements, applicable to different spatial and temporal scales. The variability and inherent uncertainty in recharge estimation motivates the recommended use of multiple methods to estimate and bound regional recharge estimates. Despite the inherent limitations of using daily gauged streamflow, recession curve displacement methods provide a convenient first-order estimate as part of a multimethod hierarchical approach to estimate watershed-scale annual recharge. The implementation of recession curve displacement recharge estimation in the United States Geologic Survey (USGS) RORA program relies on the subjective, operator-specific selection of baseflow recession events to estimate a gauge-specific recession index. This paper presents a parametric algorithm that objectively automates this tedious, subjective process, parameterizing and automating the implementation of recession curve displacement. Results using the algorithm reproduce regional estimates of groundwater recharge from the USGS Appalachian Valley and Piedmont Regional Aquifer-System Analysis, with an average absolute error of less than 2%. The algorithm facilitates consistent, completely automated estimation of annual recharge that complements more rigorous data-intensive techniques for recharge estimation. PMID- 27391932 TI - Upper and lower conjunctival fornix depth in healthy white caucasian eyes: a method of objective assessment. AB - PurposeEvaluating anti-scarring therapies require objective assessment of scarring, and knowledge of normal fornix anatomy. Measurement of conjunctival scarring has focused on inferior fornix shortening, although the superior fornix is often overlooked. There are data on normal fornix depth (FD) in South Asians, but there are no studies investigating normal conjunctival FD in white Caucasians. We designed a fornix depth measurer (FDM) for objective measurement of upper and lower conjunctival FD. The purpose of this study was to evaluate intra- and inter-observer variability, and to establish a reference for normal conjunctival FD in an ethnically white Caucasian population.Patients and methodsProspective cross-sectional study evaluating conjunctival FD in 252 clinically normal white Caucasian participants aged 20-80. Paired observers evaluated inter- and intra-observer variability. Data was analyzed using Bland Altman plots and analysis of variance.ResultsFor white Caucasian subjects, mean upper and lower conjunctival fornix depths were 15.6 mm (95% confidence interval (CI), 12.5-18.8) and 10.9 mm (95% CI, 8.0-13.7), respectively. Females have smaller FDs (upper FD 15.3 mm+/-1.6 females, 16.2 mm+/-1.4 males, P<0.001; lower FD 10.6 mm+/-1.3 females, 11.3 mm+/-1.4 males, P<0.001). There was a progressive decline in FD with age (upper fornix depth 16.3 mm+/-1.2 at age 20-29, and 15.0 mm+/-1.8 at age 80+ (P=0.04)). There was 94-100% intra-observer and inter observer agreement for upper and lower fornix measurements.ConclusionsUsing a slightly different custom-designed FDM, central conjunctival fornix depth in white Caucasian eyes appears to be similar to data previously reported in South Asian eyes. Fornix depth measurements were repeatable and reproducible. PMID- 27391933 TI - Spectral-domain optical coherence tomography findings of the macula in 500 consecutive patients with uveitis. AB - PurposeTo analyze the macular structure in a large series of consecutive patients with different types of uveitis using spectral-domain optical coherence tomography (SD-OCT).Patients and methodsFive hundred eyes of 500 consecutive patients with anterior, intermediate, posterior, and panuveitis underwent standardized macular examination using SD-OCT. Central retinal thickness (CRT), macular volume (MV), and presence of cystoid macular edema (CME), diffuse macular edema (DME), serous retinal detachment (SRD), epiretinal membrane with (ERM+) and without (ERM-) retinal surface wrinkling were determined.ResultsThe anatomic location of inflammation affected significantly CRT and MV (P<0.001, respectively), with the highest values in intermediate and panuveitis. CME was seen in 25% of all uveitic eyes, DME in 11%, SRD in 8%, ERM+ in 18%, and ERM- in 13%. CME was most frequent in intermediate (40%) and panuveitis (36%); DME was most frequent in panuveitis (18%) and posterior uveitis (17%); SRD was most frequent in panuveitis (15%) and posterior uveitis (10%); ERM+ was most frequent in panuveitis (45%) and intermediate uveitis (30%); and ERM- was most frequent in intermediate (14%) and posterior uveitis (15%).ConclusionSD-OCT of the macula is recommended for all uveitis patients. CRT, MV, and the incidence of CME were highest in intermediate and panuveitis. PMID- 27391934 TI - Is an iris claw IOL a good option for correcting surgically induced aphakia in children? A review of the literature and illustrative case study. AB - Refractive correction of aphakia in childhood can be a complex management issue following lensectomy for congenital cataract or ectopia lentis. Some children have inadequate capsular support to allow an 'in the bag' or sulcus fixated intra ocular lens (IOL). In such cases, options for refractive correction include spectacles, contact lenses, or surgically fixed IOLs. Many methods of IOL fixation have been described, but none are widely adopted in children. In recent years, the iris-fixated Artisan Aphakic IOL has gained popularity, but there is still significant concern about the rate of corneal endothelial cell loss and IOL de-enclavation. Here, we review the current literature on the use of iris-fixated IOLs in children, the published data on endothelial cell loss and de-enclavation rates. We present a case illustrating the significant improvements in quality of life, which can be seen in selected children, and also the rate of endothelial cell loss, which can be encountered after initial surgery, and a re-enclavation event. We make the case that until more data are available on normal endothelial cell decline in early childhood, in addition to age-specific rates of endothelial cell loss and de-enclavation rates following surgery, the use of iris-fixated IOLs in children will continue to be a moot point and is unlikely to be widely adopted. PMID- 27391935 TI - Surgical management of anterior capsular plaque associated with persistent pupillary membranes. PMID- 27391936 TI - Changes in pupil size following panretinal retinal photocoagulation: conventional laser vs pattern scan laser (PASCAL). AB - PurposeTo evaluate and compare the possible changes in pupil size subsequent to panretinal laser photocoagulation (PRP) via conventional laser and pattern scan laser (PASCAL).Patients and methodsForty eyes of 40 patients with diabetic retinopathy were included. 20 eyes had a PRP via conventional laser and formed Group 1. 20 eyes had a PRP via PASCAL laser and formed Group 2. The participants underwent standard ophthalmologic examination at baseline. Automated infrared pupillometry were performed at baseline and month 1.ResultsThe mean pupillary measurements (mm) for Group 1 (in the order photopic, mesopic, and scotopic conditions) were 2.88+/-0.34, 3.38+/-0.40, and 3.95+/-0.38, and changed to 3.64+/ 0.42, 4.18+/-0.42, and 4.58+/-0.48, respectively. There was significant increase in pupil size at month 1 (P<0.001, P<0.001, and P<0.00, respectively). For Group 2, they were 2.90+/-0.38, 3.43+/-0.36, and 3.90+/-0.40, and changed to 3.18+/ 0.42, 3.74+/-0.36, and 4.10+/-0.38, respectively. There was significant increase in pupil size at month 1 (P=0.018, P=0.014, and P=0.014, respectively). The pupil size increased significantly in both groups in all illumination conditions.ConclusionWe have demonstrated via automated infrared pupillary measurements that PRP may significantly increase pupil size whether it is performed with conventional laser or PASCAL laser. PMID- 27391937 TI - Manchester iStent study: 3-year results and cost analysis. AB - PurposeTo evaluate the safety, efficacy, and the cost of combined phacoemulsification and single iStent insertion in open angle glaucoma (OAG) at 3 years follow-up.MethodsThis was a prospective, uncontrolled, interventional case series. All subjects underwent single iStent implantation combined with cataract surgery by a single surgeon and were followed up over 3 years. Primary outcome measures were the reduction in intraocular pressure (IOP) and number of glaucoma drops at 1, 2, and 3 years. The costs of the procedure vs the cost of continuation of glaucoma drops were calculated and compared in patients who completed 3-years follow-up.ResultsForty-one patients were included in the study and thirty-six patients completed 3-years follow-up. Mean pre-op IOP was 21.2 mm Hg on 2.1 medications. Mean IOP was reduced to 15.9 mm Hg on 0.5 drops, 16.1 mm Hg on 1.0 drops, and 17.1 mm Hg (P<0.001) on 1.3 drops (P<0.001) at 1, 2, and 3 years, respectively. The overall cost of combined cataract surgery and iStent was estimated to be L829.32 more in total than conservative management with brand name eye drops over 3 years (L7.70 per patient per year) and L14 176.9 more if generic drops were used. (L131.3 per patient per year).ConclusionsCombined phaco iStent proved to be a safe and effective way of managing patients with OAG over our 3-year follow-up period. The cost-effectiveness of the procedure may vary depending on whether brand name or generic eye drops are used. PMID- 27391938 TI - Comparison of subthreshold micropulse laser (577 nm) treatment and half-dose photodynamic therapy in patients with chronic central serous chorioretinopathy. AB - PurposeTo compare the short-term treatment outcome of the 577 nm subthreshold micropulse laser (SML) and half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC) and persistent subretinal fluid (SRF).MethodsThis retrospective study included 100 eyes of 100 consecutive patients who were treated with the 577 nm SML (Supra Scan, Quantel Medical) (n=42) or half-dose PDT (n=58) for cCSC. The treatment was applied at the leakage sites in the fluorescein and indocyanine green angiography. The treatment success was evaluated 6 weeks after treatment using best-corrected visual acuity, central retinal thickness, and resolution of SRF in spectral domain optical coherence tomography.ResultsPatients showed treatment response more often in the SML group compared with the PDT group (treatment response after SML: 33 eyes (79%), PDT: 34 eyes (59%), P=0.036, chi2 test). The CRT decreased significantly after both treatments (mean CRT before SML: 445+/-153 MUm, after SML: 297+/-95, P<0.001; mean CRT before PDT: 398+/-88 MUm, after PDT: 322+/-93 MUm, P<0.001, Wilcoxon's signed-rank test). The decrease in CRT was statistically significantly higher in the SML group (decrease in CRT after SML: -148+/-163 MUm, after PDT: -76+/-104 MUm, P=0.041, Mann-Whitney U-test).ConclusionsBoth the half-dose PDT and the 577 nm SML are potent treatments for cCSC with persistent SRF. More patients showed treatment response to the SML treatment and SML leads to a greater decrease in CRT. PMID- 27391940 TI - Male victims of sexual assault; 10 years' experience from a Danish Assault Center. AB - This study aims to provide descriptive data regarding male victims of sexual assault seen at the Centre for Victims of Sexual Assault in Copenhagen, Denmark. All 55 male victims attending the center in the time period of March 2001 until December 2010 underwent a standardized data collection. Data included information on the victim and the sexual assault. Male victims accounted for less than 2% of the total number of visits to the center in this time period. Fifty three percent were between 15 and 24 years. In all cases the perpetrator was male, and 25% were assaulted by more than one perpetrator. Of the 62% of male victims who gave information on sexual orientation, 36% reported themselves as heterosexuals. A total of 45.5% had an alcohol intake of more than 5 units in the hours before the assault. Forty two percent reported the assault to the police. The male victims differed from female victims in several ways; they were more often assaulted by a stranger; more likely to be assaulted by more than one perpetrator; more likely being victim of drug rape; less likely to have experienced previous sexual abuse and less willing to report their assault to the police. Being victim of a sexual assault by another man is considered a taboo subject and it is likely that the dark figure of men exposed to sexual assault is much higher than it is for women. Strengthening our knowledge regarding male victims of sexual assault is necessary to improve both primary and secondary preventive measures in order to make male victims feel safe in coming forward. Male victims should have equal access to both medical and psychological help as female victims. PMID- 27391939 TI - Quality of life and functional vision concerns of children with cataracts and their parents. AB - PurposeTo identify specific health-related quality of life (HRQOL) and functional vision concerns affecting children with cataracts and common associated conditions as expressed by children or one of their parents (proxy), and HRQOL concerns affecting the parents themselves.MethodsIndividual semi-structured interviews were conducted with parents of children with cataracts (N=31) and with the children themselves (ages 5-17 years; N=16). Transcripts of recorded interviews were evaluated using NVivo software. Specific concerns were identified and coded, and broad themes were identified. The frequency of each theme was calculated, with the frequency of specific concerns within each theme.ResultsRegarding the child's experience, 6 themes were identified: Visual Function (mentioned by 16 of 16 children (100%) and by 26 of 31 parents (84%), Social (94 and 65%), Treatment (81 and 90%), Worry (75 and 10%), Emotions (63 and 68%), and Physical Discomfort (63 and 26%). Worry showed the largest discrepancy between child and their parent; although 75% children reported Worry, only 6% of parents reported that their child experienced Worry (P=0.0009). Regarding the parents' own experience, 5 themes were identified: Worry (100%), Compensation for Condition (100%), Treatment (94%), Emotions (90%), and Affects Family (52%).ConclusionsA wide range of concerns were identified from interviews of children with cataracts and their parents. Concerns reflect the impact of cataracts in physical, emotional, and social domains, and specific concerns will be used for the development of questionnaires to quantify the quality of life and functional vision effects of cataracts. PMID- 27391942 TI - The Utility of Magnetic Resonance Imaging in Assessing Patients With Pituitary Tumors Compressing the Anterior Visual Pathway. AB - BACKGROUND: Pituitary tumors are one of the most common types of intracranial neoplasms, and can cause progressive visual loss. An ongoing challenge in the management of patients with pituitary tumors is the cost, availability, and reliability of current magnetic resonance imaging (MRI) techniques to capture clinically significant incremental tumor growth. The purpose of this study was to evaluate the various MRI-based structural analyses and to explore the relationship between measures of structure and function in the afferent visual pathway of patients with pituitary tumors. METHODS: We performed a critical review of literature on MRI-based structural analyses of pituitary adenomas using PubMed, Embase, Cochrane Library, and Google Scholar. In addition, preoperative structural characteristics of the optic apparatus, optic nerve compression, and optic chiasm elevation identified as important in the literature review, were examined in 18 of our patients from October 2010 to January 2014. RESULTS: In our review of literature, a total of 443 citations were obtained from our search strategy and review of bibliographies. Eight of these studies met inclusion/exclusion criteria and were retrieved for critical review. Of the 8 included studies, only 2 studies examined the relationship between MRI-based structural measurements and postoperative visual recovery. In our small case series, MRI analysis of chiasm elevation, severity of optic nerve compression, chiasm position, height of chiasm, tumor height, and tumor volume failed to differentiate patients with postoperative visual dysfunction vs those with visual recovery (P > 0.05). CONCLUSIONS: Although MRI-based structural analysis is an important and useful tool for managing patients with pituitary tumors, there are limited objective measures shown to be predictive of postoperative visual recovery. PMID- 27391941 TI - A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins. AB - Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti inflammatory drug Nordihydroguaiaretic acid (NDGA) with human and bovine serum albumins (HSA & BSA) were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (Kb) ~105 M-1 and free energy (DeltaG) ~ -7.5 kcal.mol-1. It also binds at site II of BSA but with lesser binding affinity (Kb) ~105 M-1 and DeltaG ~ -6.5 kcal.mol-1. The negative value of DeltaG, DeltaH and DeltaS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra. PMID- 27391943 TI - An 82-Year-Old Man With Diplopia. PMID- 27391944 TI - Teaching and Practicing Neuro-Ophthalmology in Low-Resource Countries. PMID- 27391945 TI - Correction: Radiation of the Red Algal Parasite Congracilaria babae onto a Secondary Host Species, Hydropuntia sp. (Gracilariaceae, Rhodophyta). AB - [This corrects the article DOI: 10.1371/journal.pone.0097450.]. PMID- 27391946 TI - Healthcare Staff Wellbeing, Burnout, and Patient Safety: A Systematic Review. AB - OBJECTIVE: To determine whether there is an association between healthcare professionals' wellbeing and burnout, with patient safety. DESIGN: Systematic research review. DATA SOURCES: PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. RESULTS: Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an association between one or more (but not all) subscales of the burnout measures employed, and patient safety. CONCLUSIONS: Poor wellbeing and moderate to high levels of burnout are associated, in the majority of studies reviewed, with poor patient safety outcomes such as medical errors, however the lack of prospective studies reduces the ability to determine causality. Further prospective studies, research in primary care, conducted within the UK, and a clearer definition of healthcare staff wellbeing are needed. IMPLICATIONS: This review illustrates the need for healthcare organisations to consider improving employees' mental health as well as creating safer work environments when planning interventions to improve patient safety. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42015023340. PMID- 27391947 TI - Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study. AB - BACKGROUND: Multiple sclerosis (MS) has a highly heterogenic course making prediction of long term outcome very difficult. OBJECTIVE: The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset. METHODS: This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS <=2.5), moderate (EDSS 3.0-5.5) or severe (EDSS >=6.0) disability were calculated to correct for confounders. RESULTS: Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1); p<0.001). Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005), while depression (HR 3.59; CI 1.14-11.24; p = 0.028) and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036) 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability. CONCLUSION: We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms. PMID- 27391948 TI - Human immunodeficiency virus, syphilis and hepatitis C virus prevalence trends among cross-border migrant Vietnamese female sex workers in Guangxi, China. AB - BACKGROUND: Global literature indicates the burden of human immunodeficiency virus (HIV), syphilis and hepatitis C virus (HCV) has disproportionately affected cross-border migrant female sex workers (FSW). However, few studies reported the HIV risk among Vietnamese FSW at borderline areas in China. We examined five consecutive years of HIV, syphilis, and HCV prevalence and corresponding risk factors among this group in Guangxi Province of China in the current study. METHOD: Demographic and behavioral data as well as test results of blood samples for HIV/syphilis/HCV testing were collected from the annual National Sentinel Surveillance (NSS) from the year of 2010 to 2014. The prevalence trends were first examined by stratified demographic and behavioral status. Predictive models with logistic regression were further employed to identify risk predictors for HIV, syphilis and HCV combined with multiple imputation for missing data as well as restricted cubic splines for key continuous covariates. Moreover, weighted prevalence using the distribution of venue types among all FSW from the NSS survey as the standardized population was also reported. RESULTS: The overall prevalence of HIV, syphilis and HCV across the five year period was 3.2 % (95 % CI = 2.1 %,4.3 %), 6.9 % (95 % CI = 5.3 %,8. %), and 2.6 % (95 % CI = 1.6 %,3.6 %), respectively. HIV prevalence changed from 8.2 % (95 % CI = 0.5 %,15.9 %) in 2010 to 1.7 % (95 % CI = 0.4 %,3.0 %) in 2014, and the prevalence decreased notably among FSW who were younger than 25 years old, stayed less than six months, and who participated in the HIV prevention services (P < 0.05). The syphilis prevalence also ranged from 8.2 % (95 % CI = 0.5 %,15.9 %) in 2010 to 3.9 % (95 % CI = 1.9 %,5.9 %) in 2014, and the prevalence remained relatively stable among FSW who reported inconsistent condom use with clients in the past month, those who did not participate in HIV prevention services, and had lower HIV knowledge (P > 0.05). HCV prevalence increased from 0 % in 2010 to 2.2 % (95 % CI = 0.7 %, 3.7 %) in 2014. Multivariable analyses revealed that infection with HCV increased the odds of HIV and syphilis infection. Drug use (aOR = 44.0, 95C % = 16.3,129.5) increased the odds of HCV infection. CONCLUSIONS: The relatively higher HIV, syphilis and HCV prevalence among Vietnamese FSW compared to their Chinese counterparts sets a challenge for health officials at both sides. To curb the epidemic among the cross-border FSW, preventive action requires bilateral cooperation and action by health authorities of China and Vietnam. A national level response system should be launched in order to tackle the urgently ever increasing epidemic. PMID- 27391949 TI - Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia. AB - In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that nitrative stress plays a role in vascular endothelial injury in hyperhomocysteinemia, as well as induces endothelial progenitor cell injury directly. PMID- 27391950 TI - The Role of Parental Mediation and Peer Norms on the Likelihood of Cyberbullying. AB - Cyberbullying is a disturbing behavior associated with the use of communication technologies among adolescents. Many studies have been devoted to the activities of cyber victims as risk factors, while others have considered parental mediation a protective factor. However, there is a paucity of studies investigating the joint contribution of parental mediation, peer norms and risky online activities to the likelihood of being bullied on the Internet. To fill this gap, we conducted a study among a representative sample of 495 sixth to eleventh grade adolescents. We measured risky behavior online with items indicating the frequency of posting personal details, sending an insulting message and meeting face-to-face with a stranger met online. Respondents reported their perceptions about their peers. attitudes toward these risky online behaviors. We also measured three types of parental mediation: active guidance, restrictive supervision and non-intervention. Binary logistic regression findings show that risky online behaviors and peer norms regarding these behaviors had a significant effect, suggesting that the likelihood of being bullied on the Internet is associated with both risky behavior online and the norms prevalent within the adolescents. peer group. Restrictive supervision had a significant effect, implying that parents who feel their children are being bullied online may increase their oversight. The results emphasize the critical role of peers and the declining influence of parents in adolescence. PMID- 27391951 TI - Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes. AB - OBJECTIVES: To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks. METHODS: Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction >=5% at Week 52 were evaluated. Safety was assessed based on adverse event reports. RESULTS: Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction >=5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated. CONCLUSIONS: A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction >=5% with canagliflozin versus sitagliptin over 52 weeks. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812. PMID- 27391952 TI - Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit. AB - Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean+/-standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40+/-0.33 versus [vs] 2.40+/-0.55, p = 0.007), along with greater bacterial concentrations (6.13+/ 0.63 vs. 4.96+/-1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-alphaserum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-alpha: 1656+/-166 vs. 1005+/-89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression. PMID- 27391953 TI - Novel compound heterozygous mutations in CNGA1in a Chinese family affected with autosomal recessive retinitis pigmentosa by targeted sequencing. AB - BACKGROUND: About 37 genes have been reported to be involved in autosomal recessive retinitis pigmentosa, a hereditary retinal disease. However, causative genes remain unclear in a lot of cases. METHODS: Two sibs of a Chinese family with ocular disease were diagnosed in Eye and ENT Hospital of Fudan University. Targeted sequencing performed on proband to screen pathogenic mutations. PCR combined Sanger sequencing then performed on eight family members including two affected and six unaffected individuals to determine whether mutations cosegregate with disease. RESULTS: Two affected members exhibited clinical features that fit the criteria of autosomal recessive retinitis pigmentosa. Two heterozygous mutations (NM000087, p.Y82X and p.L89fs) in CNGA1 were revealed on proband. Affected members were compound heterozygotes for the two mutations whereas unaffected members either had no mutation or were heterozygote carriers for only one of the two mutations. That is, these mutations cosegregate with autosomal recessive retinitis pigmentosa. CONCLUSIONS: Compound heterozygous mutations (NM000087, p.Y82X and p.L89fs) in exon 6 of CNGA1are pathogenic mutations in this Chinese family. Of which, p.Y82X is firstly reported in patient with autosomal recessive retinitis pigmentosa. PMID- 27391955 TI - The Socioecology of Territory Size and a "Work-Around" Hypothesis for the Adoption of Farming. AB - This paper combines theory from ecology and anthropology to investigate variation in the territory sizes of subsistence oriented agricultural societies. The results indicate that population and the dependence of individuals within a society on "wild" foods partly determine the territory sizes of agricultural societies. In contrast, the productivity of an agroecosystem is not an important determinant of territory size. A comparison of the population-territory size scaling dynamics of agricultural societies and human foragers indicates that foragers and farmers face the same constraints on their ability to expand their territory and intensify their use of resources within a territory. However, the higher density of food in an agroecosystem allows farmers, on average, to live at much higher population densities than human foragers. These macroecological patterns are consistent with a "work-around hypothesis" for the adoption of farming. This hypothesis is that as residential groups of foragers increase in size, farming can sometimes better reduce the tension between an individual's autonomy over resources and the need for social groups to function to provide public goods like defense and information. PMID- 27391954 TI - Induction of Suppressor Cells and Increased Tumor Growth following Chronic Psychosocial Stress in Male Mice. AB - To study the impact of psychosocial stress on the immune system, male mice were subjected to chronic subordinate colony housing (CSC), a preclinically validated mouse model for chronic psychosocial stress. CSC substantially affected the cell composition of the bone marrow, blood, and spleen by inducing myelopoiesis and enhancing the frequency of regulatory T cells in the CD4 population. Expansion of the myeloid cell compartment was due to cells identified as immature inflammatory myeloid cells having the phenotype of myeloid-derived suppressor cells of either the granulocytic or the monocytic type. Catecholaminergic as well as TNF signaling were implicated in these CSC-induced cellular shifts. Although the frequency of regulatory cells was enhanced following CSC, the high capacity for inflammatory cytokine secretion of total splenocytes indicated an inflammatory immune status in CSC mice. Furthermore, CSC enhanced the suppressive activity of bone marrow-derived myeloid-derived suppressor cells towards proliferating T cells. In line with the occurrence of suppressor cell types such as regulatory T cells and myeloid-derived suppressor cells, transplanted syngeneic fibrosarcoma cells grew better in CSC mice than in controls, a process accompanied by pronounced angiogenesis and clustering of immature myeloid cells in the tumor tissue. In addition, tumor implantation after CSC reinforced the CSC-induced increase in myeloid-derived suppressor cells and regulatory T cell frequencies while the CSC-induced cellular changes eased off in mice without tumor. Together, our data suggest a role for suppressor cells such as regulatory T cells and myeloid-derived suppressor cells in the enhanced tumor growth after chronic psychosocial stress. PMID- 27391956 TI - Gene-specific patterns of expression variation across organs and species. AB - BACKGROUND: A comparison of transcriptional profiles derived from different tissues in a given species or among different species assumes that commonalities reflect evolutionarily conserved programs and that differences reflect species or tissue responses to environmental conditions or developmental program staging. Apparently conflicting results have been published regarding whether organ specific transcriptional patterns dominate over species-specific patterns, or vice versa, making it unclear to what extent the biology of a given organism can be extrapolated to another. These studies have in common that they treat the transcriptomes monolithically, implicitly ignoring that each gene is likely to have a specific pattern of transcriptional variation across organs and species. RESULTS: We use linear models to quantify this pattern. We find a continuum in the spectrum of expression variation: the expression of some genes varies considerably across species and little across organs, and simply reflects evolutionary distance. At the other extreme are genes whose expression varies considerably across organs and little across species; these genes are much more likely to be associated with diseases than are genes whose expression varies predominantly across species. CONCLUSIONS: Whether transcriptomes, when considered globally, cluster preferentially according to one component or the other may not be a property of the transcriptomes, but rather a consequence of the dominant behavior of a subset of genes. Therefore, the values of the components of the variance of expression for each gene could become a useful resource when planning, interpreting, and extrapolating experimental data from mouse to humans. PMID- 27391957 TI - Antifungal activity of Cleome gynandra L. aerial parts for topical treatment of Tinea capitis: an in vitro evaluation. AB - BACKGROUND: Cleome gynandra L. (Capparaceae) is an edible weed used in Uganda topically for its presumed antifungal activity against Tinea capitis. The goal of this study was to determine if this plant possesses antifungal activity in vitro, since T. capitis is a pervasive infection among especially rural children. METHODS: Antifungal activity assay was performed by Broth dilution method, and testing done on clinical isolates of three common Tinea capitis-causing fungal strains. Evaluation of in vitro antifungal activity of the ethanol and water extracts of C. gynandra was done to determine the minimum inhibitory concentrations (MICs) and the minimum fungicidal concentrations (MFCs) of the extracts. RESULTS: The MIC of C. gynandra ethanol extract ranged from 0.0313 to 0.0625 mg/ml for Trichophyton rubrum, and from 0.25 to 0.5 mg/ml for both Microsporum canis and Trichophyton mentagrophytes. The MICs of C. gynandra aqueous extract ranged between 0.125 to 0.25 mg/ml for T. rubrum, and 0.25 to 0.5 mg/ml for both M. canis and T. mentagrophytes. T. rubrum was more sensitive than M. canis (p < 0.002) and more sensitive than T. mentagrophytes (p < 0.035) to the antifungal activity of C. gynandra. T. rubrum was 6.9 times (95 % CL: 1.15 - 41.6) more likely to have a better outcome (more sensitive) than T. mentagrophytes. Cleome gynandra aqueous extract had MFC of >=0.0313 mg/ml for M. canis, >=0.0156 mg/ml for T. mentagropyhtes, and >=0.0625 mg/ml for T. rubrum. Cleome gynandra ethanol extract showed MFCs of >=0.5 mg/ml for M. canis and T. mentagrophytes, and >=0.125 mg/ml for T. rubrum. CONCLUSION: Both plant extracts demonstrated antifungal activity, shown by the MIC and MFC for the different extracts, which varied with the type of organism of the clinical fungal isolates. The ethanol extract exhibited comparable antifungal activity to the aqueous extract indicated by the MIC values seen. Conversely, after subculturing the fungal isolates, MFCs were lower for the aqueous than for the ethanol extract. PMID- 27391958 TI - Field-testing phase of the development of individual cognitive stimulation therapy (iCST) for dementia. AB - BACKGROUND: Cognitive Stimulation Therapy (CST) groups for people with dementia are available nationally, and internationally through voluntary organisations, memory services, and in residential care settings. However, groups may not be accessible or best suited for all. Individual Cognitive Stimulation Therapy (iCST) has been developed to provide another means of accessing CST. METHODS: The programme was field tested by 22 dyads (carers and people with dementia). Dyads were trained in the iCST approach and provided with a manual and accompanying resources. Researchers contacted dyads weekly to provide support and gather adherence data. Quantitative feedback about each session was also collected using 'Monitoring Progress' forms. Upon completion of their allocation sessions, researchers interviewed dyads about their experience. In total, nine dyads were followed up. Inductive thematic analysis was performed on the qualitative data. The aims of field testing were to assess the feasibility of the programme, and the appropriateness of the iCST materials. RESULTS: Sixty-two percent of the themes received an overall 'high' rating, and the majority of activities were classed as 'low' difficulty. Common barriers to completing sessions were; lack of time, illness, and motivation. Carers felt the manual and resources were 'good' and easy to use. Benefits of the programme for the person included; improvements in communication, mood, and alertness. The programme also gave carers insight into the person's abilities and interests, and provided a new channel of communication. Little support was needed to deliver the programme. CONCLUSIONS: Implementation of the iCST intervention was feasible. However, the majority of dyads completed fewer than three sessions per week. The training and support package appeared to be suitable as carers were able to deliver the intervention without intensive support. Barriers occurred largely as a result of life commitments, rather than problems with the intervention itself. This study was limited by a high loss to follow up rate. The effectiveness and cost effectiveness of iCST were investigated in a large scale randomised controlled trial (RCT). TRIAL REGISTRATION: ISRCTN65945963 Date of trial registration: 05/05/2010. PMID- 27391959 TI - A modified theoretical framework to assess implementation fidelity of adaptive public health interventions. AB - BACKGROUND: One of the major debates in implementation research turns around fidelity and adaptation. Fidelity is the degree to which an intervention is implemented as intended by its developers. It is meant to ensure that the intervention maintains its intended effects. Adaptation is the process of implementers or users bringing changes to the original design of an intervention. Depending on the nature of the modifications brought, adaptation could either be potentially positive or could carry the risk of threatening the theoretical basis of the intervention, resulting in a negative effect on expected outcomes. Adaptive interventions are those for which adaptation is allowed or even encouraged. Classical fidelity dimensions and conceptual frameworks do not address the issue of how to adapt an intervention while still maintaining its effectiveness. DISCUSSION: We support the idea that fidelity and adaptation co exist and that adaptations can impact either positively or negatively on the intervention's effectiveness. For adaptive interventions, research should answer the question how an adequate fidelity-adaptation balance can be reached. One way to address this issue is by looking systematically at the aspects of an intervention that are being adapted. We conducted fidelity research on the implementation of an empowerment strategy for dengue prevention in Cuba. In view of the adaptive nature of the strategy, we anticipated that the classical fidelity dimensions would be of limited use for assessing adaptations. The typology we used in the assessment-implemented, not-implemented, modified, or added components of the strategy-also had limitations. It did not allow us to answer the question which of the modifications introduced in the strategy contributed to or distracted from outcomes. We confronted our empirical research with existing literature on fidelity, and as a result, considered that the framework for implementation fidelity proposed by Carroll et al. in 2007 could potentially meet our concerns. We propose modifications to the framework to assess both fidelity and adaptation. The modified Carroll et al.'s framework we propose may permit a comprehensive assessment of the implementation fidelity adaptation balance required when implementing adaptive interventions, but more empirical research is needed to validate it. PMID- 27391961 TI - Production Efficiency and Market Orientation in Food Crops in North West Ethiopia: Application of Matching Technique for Impact Assessment. AB - INTRODUCTION: Agricultural technologies developed by national and international research institutions were not benefiting the rural population of Ethiopia to the extent desired. As a response, integrated agricultural extension approaches are proposed as a key strategy to transform the smallholder farming sector. Improving Productivity and Market Success (IPMS) of Ethiopian Farmers project is one of the development projects initiated by integrating productivity enhancement technological schemes with market development model. This paper explores the impact of the project intervention in the smallholder farmers' wellbeing. METHODS: To test the research hypothesis of whether the project brought a significant change in the input use, marketed surplus, efficiency and income of farm households, we use a cross-section data from 200 smallholder farmers in Northwest Ethiopia, collected through multi-stage sampling procedure. To control for self-selection from observable characteristics of the farm households, we employ Propensity Score Matching (PSM). We finally use Data Envelopment Analysis (DEA) techniques to estimate technical efficiency of farm households. RESULTS: The outcome of the research is in line with the premises that the participation of the household in the IPMS project improves purchased input use, marketed surplus, efficiency of farms and the overall gain from farming. The participant households on average employ more purchased agricultural inputs and gain higher gross margin from the production activities as compared to the non-participant households. The non-participant households on average supply less output (measured both in monetary terms and proportion of total produce) to the market as compared to their participant counterparts. Except for the technical efficiency of production in potato, project participant households are better-off in production efficiency compared with the non-participant counterparts. CONCLUSION: We verified the idea that Improving Productivity and Market Success (IPMS) of Ethiopian farmers' project has contributed for the input and out market integration and/or market oriented agricultural production. Overall, we argue that these can be seen as an experimental model with a promising potential to improve the livelihood of the poor. Furthermore, we suggest that it is worthwhile to employ integrated agricultural extension programs with further targeting in the developing world. PMID- 27391960 TI - High Expression of Cry1Ac Protein in Cotton (Gossypium hirsutum) by Combining Independent Transgenic Events that Target the Protein to Cytoplasm and Plastids. AB - Transgenic cotton was developed using two constructs containing a truncated and codon-modified cry1Ac gene (1,848 bp), which was originally characterized from Bacillus thuringiensis subspecies kurstaki strain HD73 that encodes a toxin highly effective against many lepidopteran pests. In Construct I, the cry1Ac gene was cloned under FMVde, a strong constitutively expressing promoter, to express the encoded protein in the cytoplasm. In Construct II, the encoded protein was directed to the plastids using a transit peptide taken from the cotton rbcSIb gene. Genetic transformation experiments with Construct I resulted in a single copy insertion event in which the Cry1Ac protein expression level was 2-2.5 times greater than in the Bacillus thuringiensis cotton event Mon 531, which is currently used in varieties and hybrids grown extensively in India and elsewhere. Another high expression event was selected from transgenics developed with Construct II. The Cry protein expression resulting from this event was observed only in the green plant parts. No transgenic protein expression was observed in the non-green parts, including roots, seeds and non-green floral tissues. Thus, leucoplasts may lack the mechanism to allow entry of a protein tagged with the transit peptide from a protein that is only synthesized in tissues containing mature plastids. Combining the two events through sexual crossing led to near additive levels of the toxin at 4-5 times the level currently used in the field. The two high expression events and their combination will allow for effective resistance management against lepidopteran insect pests, particularly Helicoverpa armigera, using a high dosage strategy. PMID- 27391962 TI - Bacteraemia during Transurethral Resection of the Prostate: What Are the Risk Factors and Is It More Common than We Think? AB - The aim of this work was to investigate the microbial causes, incidence, duration, risk factors and clinical implications of bacteraemia occurring during transurethral resection of the prostate (TURP) surgery to better inform prophylaxis strategies. An ethically approved, prospective, cohort study of patients undergoing TURP was conducted. Clinical information and follow-up details were collected using standardized data collection sheets. Blood was obtained for culture at 6 different time points peri-procedure. Standard of care antibiotic prophylaxis was given prior to surgery. Bacteriuria was assessed in a pre-procedure urine sample. Histopathology from all prostate chips was assessed for inflammation and malignancy. 73 patients were consented and 276 blood samples obtained. No patients developed symptomatic bacteraemia during the procedure, 17 patients developed asymptomatic bacteraemia (23.2%). Enterococcus faecalis and Pseudomonas aeruginosa were the most common organisms cultured. 10 minutes after the start of the TURP, the odds ratio (OR) of developing bacteraemia was 5.38 (CI 0.97-29.87 p = 0.05), and 20 minutes after the start of the procedure, the OR was 6.46 (CI 1.12-37.24, p = 0.03), compared to before the procedure. We also found an association between the development of intra-operative bacteraemia and recent antibiotic use (OR 4.34, CI 1.14-16.62, p = 0.032), the presence of a urinary catheter (OR 4.92, CI 1.13-21.51, p = 0.034) and a malignant histology (OR 4.90, CI 1.30-18.46, p = 0.019). There was no statistical relationship between pre operative urine culture results and blood culture results. This study shows that asymptomatic bacteraemia is commonly caused by TURP and occurs in spite of antibiotic prophylaxis. Our findings challenge the commonly held view that urine is the primary source of bacteraemia in TURP-associated sepsis and raise the possibility of occult prostatic infection as a cause of bacteraemia. More work will be needed to determine the significance of transient bacteraemia in relation to more serious complications like infective endocarditis and malignancy. PMID- 27391963 TI - Clinical and surgical risk factors in the development of proliferative vitreoretinopathy following retinal detachment surgery: a systematic review protocol. AB - BACKGROUND: Proliferative vitreoretinopathy (PVR) is a known complication of retinal detachment surgery. It has been postulated that the establishment of PVR involves inflammatory and ischaemic processes. Surgical and clinical risk factors contribute to making certain patients more vulnerable to developing PVR. The objective of this systematic review is to identify and appraise the evidence on clinical and surgical risk factors and their utility in predicting the occurrence or worsening of PVR post-surgery. METHODS: Electronic databases and grey literature will be searched dating from 1980. Studies will be eligible if they include patients that underwent retinal reattachment surgery for rhegmatogenous retinal detachment (RRD), with and without PVR, and where risk factors were measured before or during surgery. Screening, data extraction and quality assessment will be performed independently by two reviewers using pre-defined criteria. Should any models be identified, we will liaise with the Cochrane prognostic group to help define the most appropriate quality assessment criteria based on the PROBLAST tool which is in development. All findings will be tabulated and narratively synthesised. Studies presenting models or adjusted data will likely be more informative than studies reporting unadjusted results for a single risk factor. When clinically and methodologically appropriate, random effects meta-analysis will be performed. DISCUSSION: This review will systematically and comprehensively retrieve evidence to evaluate the clinical and surgical risk factors associated with PVR. The identified evidence may aid standardisation of clinical practice and more effective management for improving patient outcomes following RRD surgery and will provide a clear reference point for vitreoretinal surgeons. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035848. PMID- 27391964 TI - Functional impairment is associated with an increased risk of mortality in patients on chronic hemodialysis. AB - BACKGROUND: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of the present study was to determine the characteristics associated with functional impairment in chronic hemodialysis, and to evaluate if functional impairment represents a risk factor for reduced survival in chronic hemodialysis. METHODS: All 132 chronic hemodialysis referring to the Hemodialysis Service of the Catholic University, Rome, Italy between November 2007 and May 2015 were included. All patients underwent comprehensive geriatric assessment; functional ability was estimated using two questionnaires exploring independency in bathing, dressing, toileting, transferring, continence, feeding (ADLs), and independency in using the telephone, shopping, food preparation, housekeeping, laundering, traveling, taking medications, and handling finances (IADLs). Functional impairment was diagnosed in presence of dependence in one or more ADLs/IADLs. Mood was assessed using the 30-item Geriatric Depression Scale. Logistic regression was used to evaluate factors associated with functional impairment. The association between functional impairment and survival was assessed by Cox regression. RESULTS: ADLs impairment was present in 34 (26 %) participants, while IADLs impairment was detected in 64 (48 %) subjects. After a follow up of 90 months, 55 (42 %) patients died. In logistic regression, depressive symptoms were associated with ADLs and IADLs impairment (OR 1.12; 95 % CI = 1.02-1.23; OR 1.16; 95 % CI = 1.02 1.33; respectively). In Cox regression, ADLs impairment was associated with mortality (HR 2.47; 95 % CI-1.07-5.67) while IADLs impairment was not associated with reduced survival (HR .80; 95 % CI-.36-1.76). CONCLUSIONS: Functional impairment is associated with depressive symptoms; also, impairment in the ADLs represents a risk factor of reduced survival in chronic hemodialysis. These associations and their potential implication should be assessed in dedicated studies. PMID- 27391965 TI - Beliefs about Childhood Vaccination in the United States: Political Ideology, False Consensus, and the Illusion of Uniqueness. AB - Several contagious diseases were nearly eradicated through childhood vaccination, but some parents have decided in recent years not to fully vaccinate their children, raising new public health concerns. The question of whether and how beliefs about vaccination are linked to political ideology has been hotly debated. This study investigates the effects of ideology on perceptions of harms and benefits related to vaccination as well as judgments of others' attitudes. A total of 367 U.S. adults (131 men, 236 women; Mage = 34.92 years, range = 18-72) completed an online survey through Mechanical Turk. Results revealed that liberals were significantly more likely to endorse pro-vaccination statements and to regard them as "facts" (rather than "beliefs"), in comparison with moderates and conservatives. Whereas conservatives overestimated the proportion of like minded others who agreed with them, liberals underestimated the proportion of others who agreed with them. That is, conservatives exhibited the "truly false consensus effect," whereas liberals exhibited an "illusion of uniqueness" with respect to beliefs about vaccination. Conservative and moderate parents in this sample were less likely than liberals to report having fully vaccinated their children prior to the age of two. A clear limitation of this study is that the sample is not representative of the U.S. POPULATION: Nevertheless, a recognition of ideological sources of potential variability in health-related beliefs and perceptions is a prerequisite for the design of effective forms of public communication. PMID- 27391966 TI - Detection of Rare Antimicrobial Resistance Profiles by Active and Passive Surveillance Approaches. AB - Antimicrobial resistance (AMR) surveillance systems are generally not specifically designed to detect emerging resistances and usually focus primarily on resistance to individual drugs. Evaluating the diversity of resistance, using ecological metrics, allows the assessment of sampling protocols with regard to the detection of rare phenotypes, comprising combinations of resistances. Surveillance data of phenotypic AMR of Canadian poultry Salmonella Heidelberg and swine Salmonella Typhimurium var. 5- were used to contrast active (representative isolates derived from healthy animals) and passive (diagnostic isolates) surveillance and assess their suitability for detecting emerging resistance patterns. Although in both datasets the prevalences of resistance to individual antimicrobials were not significantly different between the two surveillance systems, analysis of the diversity of entire resistance phenotypes demonstrated that passive surveillance of diagnostic isolates detected more unique phenotypes. Whilst the most appropriate surveillance method will depend on the relevant objectives, under the conditions of this study, passive surveillance of diagnostic isolates was more effective for the detection of rare and therefore potentially emerging resistance phenotypes. PMID- 27391969 TI - Contrasting Pollinators and Pollination in Native and Non-Native Regions of Highbush Blueberry Production. AB - Highbush blueberry yields are dependent on pollination by bees, and introduction of managed honey bees is the primary strategy used for pollination of this crop. Complementary pollination services are also provided by wild bees, yet highbush blueberry is increasingly grown in regions outside its native range where wild bee communities may be less adapted to the crop and growers may still be testing appropriate honey bee stocking densities. To contrast crop pollination in native and non-native production regions, we sampled commercial 'Bluecrop' blueberry fields in British Columbia and Michigan with grower-selected honey bee stocking rates (0-39.5 hives per ha) to compare bee visitors to blueberry flowers, pollination and yield deficits, and how those vary with local- and landscape scale factors. Observed and Chao-1 estimated species richness, as well as Shannon diversity of wild bees visiting blueberries were significantly higher in Michigan where the crop is within its native range. The regional bee communities were also significantly different, with Michigan farms having greater dissimilarity than British Columbia. Blueberry fields in British Columbia had fewer visits by honey bees than those in Michigan, irrespective of stocking rate, and they also had lower berry weights and a significant pollination deficit. In British Columbia, pollination service increased with abundance of wild bumble bees, whereas in Michigan the abundance of honey bees was the primary predictor of pollination. The proportion of semi-natural habitat at local and landscape scales was positively correlated with wild bee abundance in both regions. Wild bee abundance declined significantly with distance from natural borders in Michigan, but not in British Columbia where large-bodied bumble bees dominated the wild bee community. Our results highlight the varying dependence of crop production on different types of bees and reveal that strategies for pollination improvement in the same crop can vary greatly across production regions. PMID- 27391967 TI - Ventricular assist devices as bridge to heart transplantation: impact on post transplant infections. AB - BACKGROUND: Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients. METHODS: Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant. RESULTS: Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p < 0.001), but presence of a VAD was not (HR 0.94, [95 % CI 0.38-2.32], p = 0.89, for continuous-flow devices, and HR 0.45 [0.15 - 1.34], p = 0.15, for other devices). Risk for post-transplant viral and all fungal infections was not increased in patients with VAD. One-year survival was 82.9 % (29/35) in the VAD group and 82.1 % (69/84) in the non-VAD group. All 6 patients in the VAD group that died after transplant had a history of pre-transplant VAD infection. CONCLUSION: In this nationwide cohort of heart transplant recipients, the presence of VAD at the time of transplant had no influence on the development of post-transplant infections. PMID- 27391968 TI - Distinctive Recognition of Flagellin by Human and Mouse Toll-Like Receptor 5. AB - Toll-like receptor 5 (TLR5) is a receptor of the innate immune system that recognizes flagellin from certain bacterial species and triggers an inflammatory response. The Salmonella dublin flagellin in complex with zebrafish TLR5 has been crystallized previously. In the present study, we extrapolate the structure of this complex using structure-guided mutagenesis to determine the recognition modes of human and mouse TLR5 receptors and demonstrate species-specific differences in flagellin recognition. In general, the recognition mode of the mouse receptor can be said to be more robust in comparison to that of the human receptor. All-atom molecular dynamics simulation showed differences between the two receptors within the primary binding region. Using a functional motility assay, we show that although the highly conserved area of the flagellin analyzed in this study encompasses key structural requirements for flagella formation, a direct correlation between immune recognition and structure on the level of amino acid residues is not observed. PMID- 27391970 TI - Sodium Thiosulfate Prevents Chondrocyte Mineralization and Reduces the Severity of Murine Osteoarthritis. AB - OBJECTIVES: Calcium-containing crystals participate in the pathogenesis of OA. Sodium thiosulfate (STS) has been shown to be an effective treatment in calcification disorders such as calciphylaxis and vascular calcification. This study investigated the effects and mechanisms of action of STS in a murine model of OA and in chondrocyte calcification. METHODS: Hydroxyapatite (HA) crystals stimulated murine chondrocytes and macrophages were treated with STS. Mineralization and cellular production of IL-6, MCP-1 and reactive oxygen species (ROS) were assayed. STS's effects on genes involved in calcification, inflammation and cartilage matrix degradation were studied by RT-PCR. STS was administered in the menisectomy model of murine OA, and the effect on periarticular calcific deposits and cartilage degeneration was investigated by micro-CT-scan and histology. RESULTS: In vitro, STS prevented in a dose-dependent manner calcium crystal deposition in chondrocytes and inhibited Annexin V gene expression. In addition, there was a reduction in crystal-induced IL-6 and MCP-1 production. STS also had an antioxidant effect, diminished HA-induced ROS generation and abrogated HA-induced catabolic responses in chondrocytes. In vivo, administration of STS reduced the histological severity of OA, by limiting the size of new periarticular calcific deposits and reducing the severity of cartilage damage. CONCLUSIONS: STS reduces the severity of periarticular calcification and cartilage damage in an animal model of OA via its effects on chondrocyte mineralization and its attenuation of crystal-induced inflammation as well as catabolic enzymes and ROS generation. Our study suggests that STS may be a disease-modifying drug in crystal-associated OA. PMID- 27391971 TI - Transcriptome analysis of root response to citrus blight based on the newly assembled Swingle citrumelo draft genome. AB - BACKGROUND: Citrus blight is a citrus tree overall decline disease and causes serious losses in the citrus industry worldwide. Although it was described more than one hundred years ago, its causal agent remains unknown and its pathophysiology is not well determined, which hampers our understanding of the disease and design of suitable disease management. RESULTS: In this study, we sequenced and assembled the draft genome for Swingle citrumelo, one important citrus rootstock. The draft genome is approximately 280 Mb, which covers 74 % of the estimated Swingle citrumelo genome and the average coverage is around 15X. The draft genome of Swingle citrumelo enabled us to conduct transcriptome analysis of roots of blight and healthy Swingle citrumelo using RNA-seq. The RNA seq was reliable as evidenced by the high consistence of RNA-seq analysis and quantitative reverse transcription PCR results (R(2) = 0.966). Comparison of the gene expression profiles between blight and healthy root samples revealed the molecular mechanism underneath the characteristic blight phenotypes including decline, starch accumulation, and drought stress. The JA and ET biosynthesis and signaling pathways showed decreased transcript abundance, whereas SA-mediated defense-related genes showed increased transcript abundance in blight trees, suggesting unclassified biotrophic pathogen was involved in this disease. CONCLUSIONS: Overall, the Swingle citrumelo draft genome generated in this study will advance our understanding of plant biology and contribute to the citrus breeding. Transcriptome analysis of blight and healthy trees deepened our understanding of the pathophysiology of citrus blight. PMID- 27391972 TI - Geo-spatial factors associated with infection risk among young children in rural Ghana: a secondary spatial analysis. AB - BACKGROUND: Determining the spatial patterns of infection among young children living in a malaria-endemic area may provide a means of locating high-risk populations who could benefit from additional resources for treatment and improved access to healthcare. The objective of this secondary analysis of baseline data from a cluster-randomized trial among 1943 young Ghanaian children (6-35 months of age) was to determine the geo-spatial factors associated with malaria and non-malaria infection status. METHODS: Spatial analyses were conducted using a generalized linear geostatistical model with a Matern spatial correlation function and four definitions of infection status using different combinations of inflammation (C-reactive protein, CRP > 5 mg/L) and malaria parasitaemia (with or without fever). Potentially informative variables were included in a final model through a series of modelling steps, including: individual-level variables (Model 1); household-level variables (Model 2); and, satellite-derived spatial variables (Model 3). A final (Model 4) and maximal model (Model 5) included a set of selected covariates from Models 1 to 3. RESULTS: The final models indicated that children with inflammation (CRP > 5 mg/L) and/or any evidence of malaria parasitaemia at baseline were more likely to be under 2 years of age, stunted, wasted, live further from a health facility, live at a lower elevation, have less educated mothers, and higher ferritin concentrations (corrected for inflammation) compared to children without inflammation or parasitaemia. Similar results were found when infection was defined as clinical malaria or parasitaemia with/without fever (definitions 3 and 4). Conversely, when infection was defined using CRP only, all covariates were non-significant with the exception of baseline ferritin concentration. In Model 5, all infection definitions that included parasitaemia demonstrated a significant interaction between normalized difference vegetation index and land cover type. Maps of the predicted infection probabilities and spatial random effect showed defined high- and low-risk areas that tended to coincide with elevation and cluster around villages. CONCLUSIONS: The risk of infection among young children in a malaria-endemic area may have a predictable spatial pattern which is associated with geographical characteristics, such as elevation and distance to a health facility. Original trial registration clinicaltrials.gov (NCT01001871). PMID- 27391973 TI - Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR) Is Associated with Activation of the Renin-Angiotensin System (RAS) to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension. AB - The proliferation of vascular smooth muscle cells (VSMCs), remodeling of the vasculature, and the renin-angiotensin system (RAS) play important roles in the development of essential hypertension (EH), which is defined as high blood pressure (BP) in which secondary causes, such as renovascular disease, are absent. The calcium-sensing receptor (CaSR) is involved in the regulation of BP. However, the underlying mechanisms by which the CaSR regulates BP are poorly understood. In the present study, the role of the CaSR in EH was investigated using male spontaneously hypertensive rats (SHRs) and rat and human plasma samples. The percentages of medial wall thickness to external diameter (WT%), total vessel wall cross-sectional area to the total area (WA%) of thoracic arteries, as well as the percentage of wall area occupied by collagen to total vessel wall area (CA%) were determined. Tissue protein expression and plasma concentrations of the CaSR, cyclic adenosine monophosphate (cAMP), renin, and angiotensin II (Ang II) were additionally assessed. WT%, WA%, and CA% were found to increase with increasing BP, whereas the plasma concentration of CaSR was found to decrease. With increasing BP, the levels of smooth muscle actin and calponin decreased, whereas those of osteopontin and proliferating cell nuclear antigen increased. The CaSR level negatively correlated with the levels of cAMP and Ang II, but positively correlated with those of renin. Our data suggest that reduced expression of the CaSR is correlated with activation of the RAS, which induces increased vascular remodeling and VSMC proliferation, and thereby associated with EH in the SHR model and in the Han Chinese population. Our findings provide new insights into the pathogenesis of EH. PMID- 27391974 TI - Ampelopsin Improves Insulin Resistance by Activating PPARgamma and Subsequently Up-Regulating FGF21-AMPK Signaling Pathway. AB - Ampelopsin (APL), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. Here, we explored the anti-diabetic activity of APL and elucidate the underlying mechanism of this action. In palmitate-induced insulin resistance of L6 myotubes, APL treatment markedly up- regulated phosphorylated insulin receptor substrate-1 and protein kinase B, along with a corresponding increase of glucose uptake capacity. APL treatment also increased expressions of fibroblast growth factor (FGF21) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK), however inhibiting AMPK by Compound C or AMPK siRNA, or blockage of FGF21 by FGF21 siRNA, obviously weakened APL -induced increases of FGF21 and p-AMPK as well as glucose uptake capacity in palmitate -pretreated L6 myotubes. Furthermore, APL could activate PPAR gamma resulting in increases of glucose uptake capacity and expressions of FGF21 and p-AMPK in palmitate -pretreated L6 myotubes, whereas all those effects were obviously abolished by addition of GW9662, a specific inhibitor of peroxisome proliferator- activated receptor -gamma (PPARgamma), and PPARgammasiRNA. Using molecular modeling and the luciferase reporter assays, we observed that APL could dock with the catalytic domain of PPARgamma and dose dependently up-regulate PPARgamma activity. In summary, APL maybe a potential agonist of PPARgamma and promotes insulin sensitization by activating PPARgamma and subsequently regulating FGF21- AMPK signaling pathway. These results provide new insights into the protective health effects of APL, especially for the treatment of Type 2 diabetes mellitus. PMID- 27391975 TI - Relation between distal motor latency delay and sensory action potential absence of the median nerve in carpal tunnel syndrome. AB - OBJECTIVE: To elucidate the cutoff value for distal motor latency (DML) at which sensory nerve action potentials (SNAPs) are absent in carpal tunnel syndrome (CTS) patients. METHOD: We examined 157 hands in 129 patients with CTS retrospectively. We classified the patients according to whether SNAPs were successfully obtained. Group A consisted of hands with SNAPs, while Group B consisted of hands without SNAPs. The cutoff value for DML was determined by receiver-operating characteristic curve analysis. We enrolled 130 hands with CTS for the analysis, because measurements were successful in 130 hands for compound muscle action potentials and in 82 hands for SNAPs from a total of 157 hands investigated. RESULTS: A significant correlation was observed between DML and SCV (P<0.0001, R*2=0.40). The most discriminative cutoff value for DML was 7.7ms, resulting in a sensitivity of 79.6% and specificity of 79.3%. CONCLUSION: Cases in which SNAPs are evoked despite a DML longer than 7.7ms should raise suspicion. PMID- 27391976 TI - Change of cingulum following shunt operation for hydrocephalus in a patient with a haemorrhagic stroke. PMID- 27391977 TI - Late-onset granulomatous prostatitis following intravesical bacille Calmette Guerin therapy: case report. AB - Bacille Calmette-Guerin intravesical treatment is the most effective treatment for reducing the recurrence of non-muscle-invasive urothelial carcinomas. This treatment can sometimes have side effects and serious complications. Granulomatous prostatitis is a common histological finding but it rarely has a clinical presentation. We report a case of a 75-year-old, type 2 diabetic, male patient who was diagnosed with urothelial in situ carcinoma, for which he began treatment with Bacille Calmette-Guerin instillations. Five years later the patient presented nocturia, pollakiuria, severe urgency, and intense and recurrent perineal pain associated with marked elevation of prostatic specific antigen. A prostatic biopsy was performed that showed a moderate to severe granulomatous prostatitis related to bacille Calmette-Guerin. The patient received full antituberculosis combination drugs with a favorable clinical response. PMID- 27391978 TI - Ibrutinib is an effective treatment for B-cell prolymphocytic leukaemia. PMID- 27391979 TI - Retinoblastoma-associated protein 140 as a candidate for a novel etiological gene to hypertension. AB - Gene discovery in animal models may lead to the revelation of therapeutic targets for essential hypertension as well as mechanistic insights into blood pressure (BP) regulation. Our aim was to identify a disease-causing gene for a component of polygenic hypertension contrasting inbred hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats. The chromosome segment harboring a quantitative trait locus (QTL), C16QTL, was first isolated from the rat genome via congenic strains. A candidate gene responsible for C16QTL causing a BP difference between DSS and Lewis rats was then identified using molecular analyses combining our independently-conducted total genome and gene-specific sequencings. The retinoblastoma-associated protein 140 (Rap140)/family with sequence similarity 208 member A (Fam208a) is the only candidate gene supported to be C16QTL among three genes in genome block 1 present in the C16QTL-residing interval. A mode of its actions could be to influence the expressions of genes that are downstream in a pathway potentially leading to BP regulation such as that encoding the solute carrier family 7 (cationic amino acid transporter, y+ system) member 12 (Slc7a12), which is specifically expressed in kidneys. Thus, Rap140/Fam208a probably encoding a transcription factor is the strongest candidate for a novel BP QTL that acts via a putative Rap140/Fam208a-Slc7a12-BP pathway. These data implicate a premier physiological role for Rap140/Fam208 beyond development and a first biological function for the Slc7a12 protein in any organism. PMID- 27391980 TI - A novel magnetic resonance imaging segmentation technique for determining diffuse intrinsic pontine glioma tumor volume. AB - OBJECTIVE Accurately determining diffuse intrinsic pontine glioma (DIPG) tumor volume is clinically important. The aims of the current study were to 1) measure DIPG volumes using methods that require different degrees of subjective judgment; and 2) evaluate interobserver agreement of measurements made using these methods. METHODS Eight patients from a Phase I clinical trial testing convection-enhanced delivery (CED) of a therapeutic antibody were included in the study. Pre-CED, post-radiation therapy axial T2-weighted images were analyzed using 2 methods requiring high degrees of subjective judgment (picture archiving and communication system [PACS] polygon and Volume Viewer auto-contour methods) and 1 method requiring a low degree of subjective judgment (k-means clustering segmentation) to determine tumor volumes. Lin's concordance correlation coefficients (CCCs) were calculated to assess interobserver agreement. RESULTS The CCCs of measurements made by 2 observers with the PACS polygon and the Volume Viewer auto-contour methods were 0.9465 (lower 1-sided 95% confidence limit 0.8472) and 0.7514 (lower 1-sided 95% confidence limit 0.3143), respectively. Both were considered poor agreement. The CCC of measurements made using k-means clustering segmentation was 0.9938 (lower 1-sided 95% confidence limit 0.9772), which was considered substantial strength of agreement. CONCLUSIONS The poor interobserver agreement of PACS polygon and Volume Viewer auto-contour methods highlighted the difficulty in consistently measuring DIPG tumor volumes using methods requiring high degrees of subjective judgment. k-means clustering segmentation, which requires a low degree of subjective judgment, showed better interobserver agreement and produced tumor volumes with delineated borders. PMID- 27391981 TI - Structural elucidation of dioxa-cage compounds from tetrahydroisobenzofuran-1(3H) one: analysis of NMR data and GIAO chemical shifts calculations. AB - The polycyclic compounds, especially the dioxa-cages, have attracted considerable attention in recent years. In our work, a series of 9beta-substituted 3-oxo-4,11 dioxatetracyclo[5.2.1.15,8 .02,6 ]undecane compounds were unexpectedly isolated during bromination, chlorination and epoxidation reactions of the 3-hydroxy 3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one. After careful analysis of the NMR data, the chemical shifts of the isolated and the expected products were predicted by theoretical calculations using density functional theory and gauge including atomic orbitals. The best correlation between calculated and experimental data was evaluated by comparing mean absolute errors and applying DP4 probability methodology. Results from both approaches indicated a correct structural elucidation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27391982 TI - [Not Available]. PMID- 27391983 TI - [Cognitive Behavioral Therapy for Anxiety and Depression in Patients with Parkinson's Disease]. AB - Non-motor symptoms in patients with Parkinson's disease (PD) are gaining more and more interest. Diagnosis of mental disorders in particular, such as anxiety and depression, are often not a part of the professional's diagnostic procedure in spite of the high prevalence rate. To provide these patients with comprehensive treatment, proper diagnosis and appropriate therapy are required. Cognitive Behavioral Therapy (CBT) has been one of the most efficient therapies for anxiety and depression, also in a group setting. This review compares studies that examined patients with PD diagnosed with anxiety disorders and/or depression. In eight studies, CBT in an individual setting was assessed. Three of these had a single case study design, three did not have a control group and two were randomized controlled trials. Two interventions were telephone-based and two were in a group therapy setting. Several results indicate that there is a decline in depressive symptoms as well as anxiety after CBT. There are very few randomized controlled studies on this issue. The efficacy of group treatment needs to be investigated better in order to offer patients effective treatment, keeping in kind their special circumstances. PMID- 27391985 TI - [Outcome Quality of Open General Psychiatric Inpatient Treatment at the Meso Level - an Observational Study in an Urban German General Hospital]. AB - BACKGROUND: Inpatient treatment (meso level) in psychiatric hospitals is commonly assumed to be effective. However, there is very little evidence-based data on this issue. OBJECTIVES AND METHODS: First evaluation of the outcome quality of an inpatient general psychiatric treatment in a German general hospital using multifaceted quality indicators (symptom severity, wellbeing, self-efficacy, depressive avoidance, patients' satisfaction with the treatment) was carried out. Patients with a wide range of psychiatric diagnoses (ICD-10 F2-F6) were randomly assigned to this naturalistic single-group pre-post study. For ethical and methodological reasons, only adult inpatients treated in open general psychiatric wards were enrolled. RESULTS: The sample (n = 110, 58.2 % females) had a mean age of 47.2 (SD 15.9) years. 67 (60.9 %) and 29 (26.4 %) patients had at least one or two additional psychiatric diagnoses, respectively. 84 (76.4 %) and 62 (56.4 %) patients had a minimum of one or two additional somatic diagnoses, respectively. The treatment lasted 38 (SD 36; median 28.5) days. Significant positive treatment effects for all quality indicators were found at regular hospital discharge. The effect sizes varied between Cohen's d = 0.17 - 0.62 ("intention-to-treat" population, n = 110) and d = 0.28 - 0.99 ("completer" population, n = 70). DISCUSSION AND CONCLUSION: This study provides direct evidence for the effectiveness of an open inpatient general psychiatric hospital treatment at the meso level. The results, however, are not representative for all German general psychiatric wards because of major differences between hospitals in personnel resources and framework conditions. PMID- 27391984 TI - [Muller-Hegemann's classification of depressions of 1964 as a proposal for a conceptualization of affective disorders: A critical review]. AB - Against the background of current discussions on the classification of psychiatric disorders, this study analyses and discusses the East-German psychiatrist Dietfried Muller-Hegemann's concept of a clinical classification of depressions of 1964.In his paper, Muller-Hegemann differentiated between two main forms of depression, namely the "vitally tinged depression" (= melancholy), found mainly in the depressive phases of the manic-depressive disorder, and the "depressive disgruntlement" (= dysthymia) seen in "reactive and neurotic depression", "involutional depression", and in the depressive states in psychopathic personalities. Due to a lack of sufficient biological evidence, Muller-Hegemann refrained from a purely etiological differentiation.His proposal is significant in so far as it provided a classification that could easily be used in clinical practice, and at the same time, by pointing to the traditional concept of melancholy and by calling for a differentiated psychopathology, anticipated aspects of topical interest. PMID- 27391987 TI - [Not Available]. PMID- 27391988 TI - [Not Available]. PMID- 27391986 TI - [Radiation-Induced Radiculopathy with Paresis of the Neck and Autochthonous Back Muscles with Additional Myopathy]. AB - Radiation-induced tissue damage is caused by ionizing radiation mainly affecting the skin, vascular, neuronal or muscle tissue. Early damages occur within weeks and months while late damages may occur months or even decades after radiation.Radiation-induced paresis of the spine or the trunk muscles with camptocormia or dropped-head syndrome are rare but have already been described as long-term sequelae after treatment of Hodgkin's lymphoma. The differential diagnosis includes limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy (FSHD) or lysosomal storage diseases (e. g. Acid Maltase Deficiency). We present the case of a patient with long lasting diagnostics over many months due to different inconclusive results. PMID- 27391989 TI - [Subarachnoid Hemorrhage and Isolated Brainstem Death]. AB - BACKGROUND: Worldwide there are differences in the procedure of determining brain death. An irreversible loss of all brain functions, including cerebrum, cerebellum and brainstem is mandatory for the diagnosis of brain death in Germany. On the basis of a case report some important aspects of the new recommendations of the German guidelines are discussed. CASE REPORT: We present the case of a 41-year old patient who was admitted to our clinic due to acute subarachnoid hemorrhage (SAH). Angiography revealed an aneurysm of the posterior inferior cerebellar artery. The patient was comatose without any brainstem reflexes and showed apnoea. However, on day 3, EEG showed alpha activity as a sign of residual cortical function. We diagnosed an isolated brainstem death. The next day EEG was isoelectric and brain death was confirmed. DISCUSSION: The diagnosis of isolated brainstem death does not allow a confirmation of death in Germany. Our case presents a primary infratentorial brain damage mandating additional confirmatory tests. PMID- 27391990 TI - Effect of technological factors on the activity and losses of cathepsins B, D and L during the marinating of Atlantic and Baltic herrings. AB - BACKGROUND: This study analyzes the effect of salt and acetic acid concentration, time, temperature and fish freezing on the activity and losses of cathepsins during the marinating of Atlantic and Baltic herrings. RESULTS: The highest contribution to meat general proteolytic activity was found for cathepsin D-like activity. This contribution decreased during the marinating process as a result of, among other things, cathepsin losses to brine. The methods of marinating had a significant impact on cathepsin activity losses. The average ratio of cathepsin D-like activity to L and B in brine accounted for 15:3.5:1.5, respectively. Depending on the method of calculation, cathepsin activity in brine was similar (per gram of tissue/milliliter of brine) or multiply higher (per gram protein in tissue/brine) than in the marinated herring meat. Statistical analysis demonstrated that the extent and structure of cathepsin losses were significantly correlated with the quantitative and qualitative composition of protein hydrolysis products in marinades. CONCLUSION: The presented results depict new phenomena of cathepsin losses and explain their impact on the process of fish marinating. Results allow better optimization of the process of meat ripening. The high activity of aspartyl and cysteine cathepsins in brine indicates the real feasibility of their application in the food industry for novel food design. (c) 2016 Society of Chemical Industry. PMID- 27391991 TI - Evaluation of prediction strategy and care coordination for COPD readmissions. AB - OBJECTIVES: Factors that influence the likelihood of readmission for chronic obstructive pulmonary disease (COPD) patients and the impact of posthospital care coordination remain uncertain. LACE index (L = length of stay, A = Acuity of admission; C = Charlson comorbidity index; E = No. of emergency department (ED) visits in last 6 months) is a validated tool for predicting 30-days readmissions for general medicine patients. We aimed to identify variables predictive of COPD readmissions including LACE index and determine the impact of a novel care management process on 30-day all-cause readmission rate. METHODS: In a case control design, potential readmission predictors including LACE index were analyzed using multivariable logistic regression for 461 COPD patients between January-October 2013. Patients with a high LACE index at discharge began receiving care coordination in July 2013. We tested for association between readmission and receipt of care coordination between July-October 2013. Care coordination consists of a telephone call from the care manager who: 1) reviews discharge instructions and medication reconciliation; 2) emphasizes importance of medication adherence; 3) makes a follow-up appointment with primary care physician within 1-2 weeks and; 4) makes an emergency back-up plan. RESULTS: COPD readmission rate was 16.5%. An adjusted LACE index of >= 13 was not associated with readmission (p = 0.186). Significant predictors included female gender (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.29-0.91, p = 0.021); discharge to skilled nursing facility (OR 3.03, 95% CI 1.36-6.75, p = 0.007); 4-6 comorbid illnesses (OR 9.21, 95% CI 1.17-76.62, p = 0.035) and >= 4 ED visits in previous 6 months (OR 6.40, 95% CI 1.25-32.87, p = 0.026). Out of 119 patients discharged between July-October 2013, 41% received the care coordination. The readmission rate in the intervention group was 14.3% compared to 18.6% in controls (p = 0.62). CONCLUSIONS: Factors influencing COPD readmissions are complex and poorly understood. LACE index did not predict 30-days all-cause COPD readmissions. Posthospital care coordination for transition of care from hospital to the community showed a 4.3% reduction in the 30-days all-cause readmission rate which did not reach statistical significance (p = 0.62). PMID- 27391992 TI - Children and HIV - a hop (hopefully), a skip (lamentably) and a jump (ideally)? PMID- 27391993 TI - Promoting uptake of child HIV testing: an evaluation of the role of a home visiting program for orphans and vulnerable children in South Africa. AB - HIV counseling and testing (HCT) is critical for children in generalized epidemic settings, but significant shortfalls in coverage persist, notably among orphans and others at disproportionate risk of infection. This study investigates the impact of a home visiting program in South Africa on orphaned and vulnerable children's uptake of HCT. Using propensity score matching, survey data for children receiving home visits from trained community-based care workers were compared to data from children living in similar households that had not yet received home visits (n = 1324). Home visits by community-based care workers increased the odds of a child being tested by 97% (OR = 1.97, 95% CI = 1.34 2.92). The home visitation program had an especially pronounced effect on orphans, more than doubling their odds of being tested (OR = 2.12, 95% CI = 1.00 4.47) compared to orphans living in similar households that did not receive home visits. Orphan status alone had no effect on HCT independent of program exposure, suggesting that the program was uniquely able to increase testing in this subgroup. Results highlight the potential for increasing HCT access among children at high risk through targeted community-based initiatives. PMID- 27391994 TI - Underage and underserved: reaching young women who sell sex in Zimbabwe. AB - Young women who sell sex (YWSS) in Southern Africa are highly vulnerable to HIV, as the risks of being young and female in a high prevalence setting coalesce with those of commercial sex. YWSS are less able to negotiate safe sex, more likely to have higher risk partners, and less likely to use available health services compared to older sex workers. In Zimbabwe's national HIV programme for sex workers, fewer than 1% of clients were 15-29. We developed monthly interactive workshops for YWSS based on an Activity Pack consisting of 21 sessions organised into six modules. The aim was to encourage YWSS' interaction with each other, build their trust, confidence and skills, and encourage uptake of clinical services. We conducted a process evaluation to assess programme strengths, identify challenges, and recommend changes. This paper presents findings synthesising programme records with qualitative data and discusses feasibility, acceptability, and outputs during the pilot phase. In total, 143 YWSS attended meetings and most were from the target 15-19-year-old age group. Participants enjoyed the sessions and reported improved cooperation, willingness to negotiate with clients, and self-reflection about their futures. Staff found facilitating sessions easy and activities clear and appropriate. Challenges included identifying appropriate referrals, initial recruitment of women in some sites, and managing participants' requests for financial compensation. The number of clients aged 15-19 increased at sex worker clinics in all sites. This programme is the first to target YWSS in Zimbabwe to address their disproportionately low service use. It proved feasible to staff and acceptable to participants over a one-year period. Given enhanced vulnerability of YWSS, this programme provides one workable model for reaching this underserved group. PMID- 27391995 TI - I don't know what I am doing because I am doing everything: perceptions and experiences of nurses about HIV counselling and testing among children in Free State Province, South Africa. AB - Although HIV/AIDS constitute a significant health burden among children in South Africa, testing and counselling of exposed children are inadequate. It is therefore imperative that factors relating to paediatric HCT services offered by health workers are examined. This study was conducted to explore and describe the perceptions and experiences of trained professional nurses regarding HIV counselling and testing among children. We conducted six focus group discussions among trained professional nurses in health facilities in a district in Free State Province, South Africa. All verbatim transcripts were analysed with a thematic approach and emergent codes were applied. Forty-seven trained professional nurses participated in the study and two of them were males. The age of the participants ranges from 38 to 60 years while the median age was 50 years. Most participants in the focus groups explained how HCT occurs during regular health talks and that lay counsellors are doing most of the counselling. While a few participants thought that children should not be bothered with HCT, most of them seek consent from caregivers for HIV test for children. While children whose parents are negative are usually not tested, most children are tested only when they become ill. Identified barriers to HCT among children include refusal of consent, work overload, lack of encouragement, and poor record keeping. Participants recommended improvement of issues relating to community mobilization and increasing trained staff strength for optimal paediatric HCT service delivery. Developing guidance and policies with respect to obtaining consent, recruiting more health providers, and addressing structural issues in the society to reduce stigma and discrimination were identified as key priority issues by majority of the participants. The perspectives of these participants who provide paediatric HCT services offer vital insight which may be useful to inform policy interventions. PMID- 27391996 TI - Closing the delivery gaps in pediatric HIV care in Togo, West Africa: using the care delivery value chain framework to direct quality improvement. AB - Providing quality care for all children living with HIV/AIDS remains a global challenge and requires the development of new healthcare delivery strategies. The care delivery value chain (CDVC) is a framework that maps activities required to provide effective and responsive care for a patient with a particular disease across the continuum of care. By mapping activities along a value chain, the CDVC enables managers to better allocate resources, improve communication, and coordinate activities. We report on the successful application of the CDVC as a strategy to optimize care delivery and inform quality improvement (QI) efforts with the overall aim of improving care for Pediatric HIV patients in Togo, West Africa. Over the course of 12 months, 13 distinct QI activities in Pediatric HIV/AIDS care delivery were monitored, and 11 of those activities met or exceeded established targets. Examples included: increase in infants receiving routine polymerase chain reaction testing at 2 months (39-95%), increase in HIV exposed children receiving confirmatory HIV testing at 18 months (67-100%), and increase in patients receiving initial CD4 testing within 3 months of HIV diagnosis (67 100%). The CDVC was an effective approach for evaluating existing systems and prioritizing gaps in delivery for QI over the full cycle of Pediatric HIV/AIDS care in three specific ways: (1) facilitating the first comprehensive mapping of Pediatric HIV/AIDS services, (2) identifying gaps in available services, and (3) catalyzing the creation of a responsive QI plan. The CDVC provided a framework to drive meaningful, strategic action to improve Pediatric HIV care in Togo. PMID- 27391997 TI - Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal. AB - For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver-child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL >= 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL <= 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver-child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information-motivation-behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child's immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment administration by healthcare workers during monthly clinic visits. PMID- 27391998 TI - "It's because they care": understanding pathways to classroom concentration problems among HIV-affected children and youth in Western Kenya. AB - Children and young people living in households affected by HIV are experiencing poorer educational outcomes compared to their peers. This article explores how different forms of marginalisation interface and manifest themselves in classroom concentration problems, undermining their education. This mixed qualitative methods study was conducted with teachers and pupils from three primary and three secondary schools in the Siaya County of Western Kenya. Specifically, it involved 18 teachers through individual interviews and 51 HIV-affected children and youth through individual interviews (n = 47) and Photovoice (n = 51). Verbatim transcripts were imported into NVivo10 for thematic indexing and analysis. The analysis revealed three core pathways to classroom concentration problems amongst HIV-affected pupils. One, a general 'lack of care' and neglect in the context of household poverty and illness, meant that many of the participating pupils went to school hungry, unable to follow classes. Others were teased by peers for looking visibly poor, and felt anxious when in school. Two, some HIV-affected pupils play a key role in keeping their household afloat, generating food and income as well as providing practical support. 'Caregiving' pupils often reported coming to school exhausted, with limited physical and mental energy left for learning. Three, many participating pupils had their minds at home ('caring about'). They were concerned about sick or frail household members, thinking about their next meal and care needs. Although the pupils demonstrated an admirable attentiveness to the needs of others, this came at a heavy price, namely their ability to concentrate in class. The paper argues that care ethics, household poverty and familial HIV are central to understanding the classroom concentration problems of HIV-affected pupils. To ensure school-going children and youth affected by HIV have the same opportunities as their peers, education initiatives must simultaneously alleviate both household poverty and other challenges pertaining to familial HIV. PMID- 27391999 TI - Resilience in perinatal HIV+ adolescents in South Africa. AB - Increasing numbers of perinatally HIV (PHIV+)-infected youth are surviving into adulthood with better access to treatment. However, few studies examine positive outcomes in the face of adversity (resilience) for PHIV+ youth. Social Action Theory (SAT) provided the theoretical framework for this study of PHIV + youth in South Africa (SA), allowing examination of contextual, social, and self regulatory factors that influence behavioral health. Data were from youth and caregiver baseline interviews, simply pooled from a pilot (N=66) and larger (n=111) randomized control trial (RCT) of the VUKA Family program. For this analysis, outcomes included emotional and behavioral functioning (total difficulties), and prosocial behaviors. Potential SAT correlates included socio demographics; caregiver health and mental health; parent-child relationship factors; stigma, and child coping, support; and self-esteem. Regression analyses adjusted for age, gender, and study revealed significant associations at the contextual, social, and self-regulation level. Lower total child difficulties scores were associated with lower caregiver depression (beta = 3.906,p < .001), less caregiver-reported communication about difficult issues (beta = 1.882, p = .009) and higher youth self-esteem (beta = -0.119, p = .020). Greater prosocial behaviors were associated with greater caregiver-reported communication (beta = 0.722, p = .020) and child use of wishful thinking for coping (beta = 5.532, p = .009). Less youth depression was associated with higher caregiver education (beta =-0.399, p = .010), greater caregiver supervision (beta = -1.261, p = .012), more social support seeking (beta = -0.453, p = .002), higher youth self-esteem (beta = -0.067, p < .001), lower internalized stigma (beta = 0.608, p = .040), and child use of resignation for coping (beta = 1.152, p = .041). Our data support evidence-based family interventions that also promote youth self-regulation skills to enhance the health and mental health of PHIV+ youth. PMID- 27392000 TI - Shortcomings of adherence counselling provided to caregivers of children receiving antiretroviral therapy in rural South Africa. AB - In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors. PMID- 27392001 TI - Analysis of the social and psychosocial factors associated with adherence to antiretroviral therapy in adolescents with perinatal HIV-1 infection in Panama from a gender perspective. AB - Adherence is vital for an effective antiretroviral treatment. This cross sectional study explored social and psychosocial factors associated with adherence among adolescents with perinatal human immunodeficiency virus type 1 infection in Panama from a gender perspective. A questionnaire developed for the study was applied to 38 adolescent patients (20 female, 18 male; median age, 14 years). Thirty-two patients (86%; one missing response) still depended on an adult to remember taking their medication, among whom 28 relied on a female relative. Although 18 (47%) patients reported to become ill no more than once a year, only 10 (26%) patients showed an undetectable viral load, and 4 (11%) patients showed no CD4 suppression. Seventeen (45%) patients recalled correctly their medication. During the week prior to the interview, 26 patients (68%) reported that they had missed at least one dose. When asked the reason for missing a dose, 23 out of 34 (68%; 4 missing responses) patients responded, "I forgot". Female patients gave more excuses for missing doses (mean +/- SD number of excuses per female, 2.4 +/- 2; per male, 1.2 +/- 1; p = .02), while more male than female patients described an action plan if they ran out of medication (13 vs. 8; p = .05). Educational programs involving patients and also family members are warranted to improve adherence. PMID- 27392002 TI - Achieving equity in HIV-treatment outcomes: can social protection improve adolescent ART-adherence in South Africa? AB - Low ART-adherence amongst adolescents is associated with morbidity, mortality and onward HIV transmission. Reviews find no effective adolescent adherence-promoting interventions. Social protection has demonstrated benefits for adolescents, and could potentially improve ART-adherence. This study examines associations of 10 social protection provisions with adherence in a large community-based sample of HIV-positive adolescents. All 10-19-year-olds ever ART-initiated in 53 government healthcare facilities in a health district of South Africa's Eastern Cape were traced and interviewed in 2014-2015 (n = 1175 eligible). About 90% of the eligible sample was included (n = 1059). Social protection provisions were "cash/cash in kind": government cash transfers, food security, school fees/materials, school feeding, clothing; and "care": HIV support group, sports groups, choir/art groups, positive parenting and parental supervision/monitoring. Analyses used multivariate regression, interaction and marginal effects models in SPSS and STATA, controlling for socio-demographic, HIV and healthcare-related covariates. Findings showed 36% self-reported past-week ART non-adherence (<95%). Non-adherence was associated with increased opportunistic infections (p = .005, B .269, SD .09), and increased likelihood of detectable viral load at last test (>75 copies/ml) (aOR 1.98, CI 1.1-3.45). Independent of covariates, three social protection provisions were associated with reduced non-adherence: food provision (aOR .57, CI .42-.76, p < .001); HIV support group attendance (aOR .60, CI .40 .91, p < .02), and high parental/caregiver supervision (aOR .56, CI .43-.73, p < .001). Combination social protection showed additive benefits. With no social protection, non-adherence was 54%, with any one protection 39-41%, with any two social protections, 27-28% and with all three social protections, 18%. These results demonstrate that social protection provisions, particularly combinations of "cash plus care", may improve adolescent adherence. Through this they have potential to improve survival and wellbeing, to prevent HIV transmission, and to advance treatment equity for HIV-positive adolescents. PMID- 27392003 TI - Equity in adherence to antiretroviral therapy among economically vulnerable adolescents living with HIV in Uganda. AB - Studies from sub-Saharan Africa indicate that children made vulnerable by poverty have been disproportionately affected by HIV with many exposed via mother-to child transmission. For youth living with HIV, adherence to life-saving treatment regimens are likely to be affected by the complex set of economic and social circumstances that challenge their families and also exacerbate health problems. Using baseline data from the National Institute of Child and Human Development (NICHD) funded Suubi+Adherence study, we examined the extent to which individual and composite measures of equity predict self-reported adherence among Ugandan adolescents aged 10-16 (n = 702) living with HIV. Results showed that greater asset ownership, specifically familial possession of seven or more tangible assets, was associated with greater odds of self-reported adherence (OR 1.69, 95% CI: 1.00-2.85). Our analyses also indicated that distance to the nearest health clinic impacts youth's adherence to an ARV regimen. Youth who reported living nearest to a clinic were significantly more likely to report optimal adherence (OR 1.49, 95% CI: 0.92-2.40). Moreover, applying the composite equity scores, we found that adolescents with greater economic advantage in ownership of household assets, financial savings, and caregiver employment had higher odds of adherence by a factor of 1.70 (95% CI: 1.07-2.70). These findings suggest that interventions addressing economic and social inequities may be beneficial to increase antiretroviral therapy (ART) uptake among economically vulnerable youth, especially in sub-Saharan Africa. This is one of the first studies to address the question of equity in adherence to ART among economically vulnerable youth with HIV. PMID- 27392004 TI - Social support as a protective factor for children impacted by HIV/AIDS across varying living environments in southern Africa. AB - The literature on the psychological well-being of children impacted by HIV/AIDS in Africa highlights increased vulnerability due to loss of parents and environmental stressors (e.g., hunger). Research shows that the lack of attachment and social support due to loss limits the grieving process in children. Access to trusting adults and social support through caregivers can be an important protective factor to allow for coping and better emotional adjustment in the future. This study examined social support systems across varying living environments to determine if social support promoted higher levels of well-being in children orphaned and made vulnerable by HIV/AIDS. The participants included 100 children from a small targeted population in southern Africa who receive varying levels of support from a private not-for-profit organization. Children's well-being was assessed through the Psycho-Social Adjustment Scale-Adolescents developed specifically for vulnerable child populations in Africa. Children were individually interviewed either on their homestead, school or hostel. Data demonstrated that children who do not share their feelings had significantly lower measures of positive well-being (M = 2.61 (0.87) vs. M = 3.10 (0.57), d = 0.60). Children with trusted adults were significantly more likely to share their feelings and had lower incidence of hunger (49.1% vs. 62.5%), suicide ideation (15.1% vs. 62.5%) and witnessing violence (69.8% vs. 87.5%). Sharing feelings with caregivers was more pronounced among children who had greater access to trusted adults and correlated with stronger attachment scores (r = .30, p < .01). An important component to decrease levels of anxiety and depression in this vulnerable population is providing access to trusted individuals. Social support interventions are discussed. PMID- 27392005 TI - Do not forget the boys - gender differences in children living in high HIV affected communities in South Africa and Malawi in a longitudinal, community based study. AB - Gender is an important factor in child development. Especially in sub-Saharan Africa, girls have often been shown to be less likely to access education compared to boys. The consequence of this has been that that programmes addressing child development are often aimed at girls in order to redress gender imbalances. This study examines the effect of gender on the development of children attending community-based organisations in high HIV-affected areas, and explores whether community-based organisation attendance was associated with any changes in gender differences over time. Baseline data from 989 children and 12 15 month follow from 854 (86% response rate) were used to examine gender differences in children from Malawi and South Africa. At baseline, where there were differences by gender, these tended to disadvantage boys. It was found that boys were significantly more often found to be subjected to violence. Boys showed worse performance at school and more behavioural problems than girls. These gender differences persisted from baseline to follow-up. At follow-up, boys self reported significantly worse average quality of life than girls. Only harsh discipline differed by gender in progression over time: boys experienced a stronger reduction in harsh physical discipline than girls from baseline to follow-up. Since harsh discipline was associated with boys' worse educational outcomes and behavioural problems, our data cautiously suggests that gender differences could be reduced over time. In conclusion, our data suggests that, perhaps due to the narrow equity approach focusing on provision for girls, boys may be overlooked. As a result, there are some specific experiences where boys are generally worse off. These differences have distinct ramifications for the educational and emotional development of boys. A broader equity approach to child development might be warranted to ensure that the needs of both girls and boys are considered, and that boys are not overlooked. PMID- 27392006 TI - The power of siblings and caregivers: under-explored types of social support among children affected by HIV and AIDS. AB - Children affected by HIV and AIDS have significantly higher rates of mental health problems than unaffected children. There is a need for research to examine how social support functions as a source of resiliency for children in high HIV prevalence settings such as South Africa. The purpose of this research was to explore how family social support relates to depression, anxiety, and post traumatic stress (PTS). Using the ecological model as a frame, data were drawn from a 2011 cross-sectional study of 1380 children classified as either orphaned by AIDS and/or living with an AIDS sick family member. The children were from high-poverty, high HIV-prevalent rural and urban communities in South Africa. Social support was analyzed in depth by examining the source (e.g. caregiver, sibling) and the type (e.g. emotional, instrumental, quality). These variables were entered into multiple regression analyses to estimate the most parsimonious regression models to show the relationships between social support and depression, anxiety, and PTS symptoms among the children. Siblings emerged as the most consistent source of social support on mental health. Overall caregiver and sibling support explained 13% variance in depression, 12% in anxiety, and 11% in PTS. Emotional support was the most frequent type of social support associated with mental health in all regression models, with higher levels of quality and instrumental support having the strongest relation to positive mental health outcomes. Although instrumental and quality support from siblings were related to positive mental health, unexpectedly, the higher the level of emotional support received from a sibling resulted in the child reporting more symptoms of depression, anxiety, and PTS. The opposite was true for emotional support provided via caregivers, higher levels of this support was related to lower levels of all mental health symptoms. Sex was significant in all regressions, indicating the presence of moderation. PMID- 27392007 TI - Exploring the potential of a family-based prevention intervention to reduce alcohol use and violence within HIV-affected families in Rwanda. AB - HIV-affected families report higher rates of harmful alcohol use, intimate partner violence (IPV) and family conflict, which can have detrimental effects on children. Few evidence-based interventions exist to address these complex issues in Sub-Saharan Africa. This mixed methods study explores the potential of a family-based intervention to reduce IPV, family conflict and problems related to alcohol use to promote child mental health and family functioning within HIV affected families in post-genocide Rwanda. A family home-visiting, evidence-based intervention designed to identify and enhance resilience and communication in families to promote mental health in children was adapted and developed for use in this context for families affected by caregiver HIV in Rwanda. The intervention was adapted and developed through a series of pilot study phases prior to being tested in open and randomized controlled trials (RCTs) in Rwanda for families affected by caregiver HIV. Quantitative and qualitative data from the RCT are explored here using a mixed methods approach to integrate findings. Reductions in alcohol use and IPV among caregivers are supported by qualitative reports of improved family functioning, lower levels of violence and problem drinking as well as improved child mental health, among the intervention group. This mixed methods analysis supports the potential of family-based interventions to reduce adverse caregiver behaviors as a major mechanism for improving child well-being. Further studies to examine these mechanisms in well-powered trials are needed to extend the evidence-base on the promise of family-based intervention for use in low- and middle-income countries. PMID- 27392008 TI - What do we know about children living with HIV-infected or AIDS-ill adults in Sub Saharan Africa? A systematic review of the literature. AB - Millions of children in Sub-Saharan Africa live with adults, often parents, who are HIV-infected or ill due to AIDS. These children experience social, emotional, and health vulnerabilities that overlap with, but are not necessarily the same as, those of orphans or other vulnerable children. Despite their distinctive vulnerabilities, research aimed at understanding the situation of these children has been limited until very recently. This review summarizes the state of knowledge based on a systematic search of PubMed and Web of Science that identified 47 empirical research articles that examined either the population prevalence of children living with HIV-infected or AIDS-sick adults, or the consequences of adult HIV infection or AIDS illness for child well-being. This review confirms that this population of children is substantial in size, and that the vulnerabilities they experience are multi-faceted, spanning physical and emotional health and schooling. Mechanisms were examined empirically in only a small number of studies, but encompass poverty, transmission of opportunistic infections, care for unwell adults, adult distress, AIDS stigma, lack of social support, maternal breastfeeding issues, and vertical HIV transmission. Some evidence is provided that infants, adolescents, children with infected or ill mothers, and children living with severely ill adults are particularly vulnerable. Future research would benefit from more attention to causal inference and further characterization of processes and circumstances related to vulnerability and resilience. It would also benefit from further study of variation in observed associations between adult HIV/AIDS and child well-being based on characteristics such as age, sex, kinship, severity of illness, TB co infection, disclosure, and serostatus awareness. Almost one-quarter of the studies reviewed did not investigate variation based on any of these factors. More nuanced understanding of the short- and long-term effects of adult HIV on children's needs and circumstances will be important to ongoing discussions about equity in policies and interventions. PMID- 27392009 TI - Caregiver supportive policies to improve child outcomes in the wake of the HIV/AIDS epidemic: an analysis of the gap between what is needed and what is available in 25 high prevalence countries. AB - In the wake of the HIV/AIDS epidemic, caregivers are struggling to support HIV affected children. For reasons of equity and efficiency, their needs can be best met through strong social protections and policies. This paper presents a conceptual framework to help address the needs of HIV-affected caregivers and to prioritize policies. We describe the needs that are common across diverse caregiving populations (e.g., economic security); the needs which are intensified (e.g., leave to care for sick children) or unique to providing care to HIV affected children (e.g., ARV treatment). The paper then explores the types of social policies that would facilitate families meeting these needs. We outline a basic package of policies that would support HIV-affected families, and would meet goals agreed to by national governments. We examine the availability of these policies in 25 highly affected countries in sub-Saharan Africa. The majority of countries guarantee short-term income protection during illness, free primary school, and educational inclusion of children with special needs. However, there are significant gaps in areas critical to family economic security and healthy child development. Fewer than half of the countries we analyzed guarantee a minimum wage that will enable families to escape poverty; only six have eliminated tuition fees for secondary school; and only three offer paid leave to care for sick children. Filling these policy gaps, as well as making mental health and social services more widely available, is essential to support caregiving by families for HIV-affected children. As part of the HIV agenda, the global community can help national governments advance towards their policy targets. This would provide meaningful protection for families affected by HIV, as well as for millions of other vulnerable families and children across the region. PMID- 27392010 TI - Caregiver satisfaction with paediatric HIV treatment and care in Nigeria and equity implications for children living with HIV. AB - Caregiver satisfaction has the potential to promote equity for children living with HIV, by influencing health-seeking behaviour. We measured dimensions of caregiver satisfaction with paediatric HIV treatment in Nigeria, and discuss its implications for equity by conducting facility-based exit interviews for caregivers of children receiving antiretroviral therapy in 20 purposively selected facilities within 5 geopolitical zones. Descriptive analysis and factor analysis were performed. Due to the hierarchical nature of the data, multilevel regression modelling was performed to investigate relationships between satisfaction factors and socio-demographic variables. Of 1550 caregivers interviewed, 63% (95% CI: 60.6-65.4) reported being very satisfied overall; however, satisfaction varied in some dimensions: only 55.6% (53.1-58.1) of caregivers could talk privately with health workers, 56.9% (54.4-59.3) reported that queues to see health workers were too long, and 89.9% (88.4-91.4) said that some health workers did not treat patients living with HIV with sufficient respect. Based on factor analysis, two underlying factors, labelled Availability and Attitude, were identified. In multilevel regression, the satisfaction with availability of services correlated with formal employment status (p < .01), whereas caregivers receiving care in private facilities were less likely satisfied with both availability (p < .01) and attitude of health workers (p < .05). State and facility levels influenced attitudes of the health workers (p < .01), but not availability of services. We conclude that high levels of overall satisfaction among caregivers masked dissatisfaction with some aspects of services. The two underlying satisfaction factors are part of access typology critical for closing equity gaps in access to HIV treatment between adults and children, and across socio-economic groups. PMID- 27392011 TI - The relationships between HIV stigma, emotional status, and emotional regulation among HIV-affected children in rural China. AB - Children affected by HIV/AIDS have unique psychosocial needs that often go unaddressed in traditional treatment approaches. They are more likely than unaffected peers to encounter stigma, including overt discriminatory behaviors, as well as stereotyped attitudes. In addition, HIV-affected children are at risk for experiencing negative affect, including sadness and depression. Previous studies have identified a link between HIV stigma and the subsequent emotional status of children affected by HIV/AIDS. However, limited data are available regarding protective psychological factors that can mitigate the effects of HIV stigma and thus promote resiliency for this vulnerable population. Utilizing data from 790 children aged 6-17 years affected by parental HIV in rural central China this study aims to examine the association between HIV stigma, including both enacted and perceived stigma, and emotional status among HIV-affected children, as well as to evaluate the mediating effects of emotional regulation on the relationship between HIV stigma and emotional status. In addition, the moderating role of age is tested. Multiple regression was conducted to test the mediation model. We found that the experience of HIV stigma had a direct positive effect on negative emotions among children affected by HIV. Emotional regulation offers a level of protection, as it mediated the impact of HIV stigma on negative emotions. Moreover, age was found to moderate the relationship between perceived stigma and negative emotions. A significant interaction between perceived stigma and age suggested that negative emotions increase with age among those who perceived a higher level of stigmatization. Results suggest that children affected by HIV may benefit from interventions designed to enhance their capacity to regulate emotions and that health professionals should be aware of the link between stigma and negative emotion in childhood and adolescence and use the knowledge to inform their treatments with this population. PMID- 27392012 TI - Child-street migration among HIV-affected families in Kenya: a mediation analysis from cross-sectional data. AB - Within Kenya, an estimated quarter of a million children live on the streets, and 1.8 million children are orphaned. In this study, we analyze how HIV contributes to the phenomenon of child-street migration. We interviewed a random community sample of caregiving women (n = 1974) in Meru County, Kenya, using a structured questionnaire in summer 2015. Items included reported HIV prevalence of respondent and her partner, social support, overall health, school enrollment of biologically related children and whether the respondent has a child currently living on the streets. Controlling for alcohol use, education, wealth, age and household size, we found a positive-graded association between the number of partners living with HIV and the probability that a child lives on the street. There was little difference in the odds of a child living on the street between maternally affected and paternally affected households. Lower maternal social support, overall health and school enrollment of biologically related children mediated 14% of the association between HIV-affected households and reporting child-street migration. Street-migration of children is strongly associated with household HIV, but the small percentage of mediated effect presents a greater need to focus on interactions between household and community factors in the context of HIV. Programs and policies responding to these findings will involve targeting parents and children in HIV-affected households, and coordinate care between clinical providers, social service providers and schools. PMID- 27392013 TI - Comment on "In Silico Modeling of Gastrointestinal Drug Absorption: Predictive Performance of Three Physiologically-Based Absorption Models". PMID- 27392014 TI - Graphene nanoribbons anchored to SiC substrates. AB - Graphene nanoribbons are quasi-one-dimensional planar graphene allotropes with diverse properties dependent on their width and types of edges. Graphene nanoribbons anchored to substrates is a hybrid system, which offers novel opportunities for property modifications as well as experimental control. Here we present electronic structure calculations of zigzag graphene nanoribbons chemically attached via the edges to the Si or C terminated surfaces of a SiC substrate. The results show that the edge characteristics are rather robust and the properties are essentially determined by the individual nanoribbon. While the localized spin polarization of the graphene nanoribbon edge atoms is not significantly affected by the substrate, secondary energy gaps in the highest conduction and lowest valence region may emerge in the anchored structures. The van der Waals interaction together with the electrostatic interactions due to the polarity of the surface bonds are found to be important for the structure parameters and energy stability. PMID- 27392016 TI - Low-Level Laser Therapy (904 nm) Counteracts Motor Deficit of Mice Hind Limb following Skeletal Muscle Injury Caused by Snakebite-Mimicking Intramuscular Venom Injection. AB - Myotoxins present in Bothrops venom disrupt the sarcolemma of muscle fibers leading to the release of sarcoplasmic proteins and loss of muscle homeostasis. Myonecrosis and tissue anoxia induced by vascularization impairment can lead to amputation or motor functional deficit. The objective of this study was to investigate the dynamic behavior of motor function in mice subjected to injection of Bothrops jararacussu venom (Bjssu) and exposed to low-level laser therapy (LLLT). Male Swiss mice received Bjssu injection (830 MUg/kg) into the medial portion of the right gastrocnemius muscle. Three hours later the injected region was irradiated with diode semiconductor Gallium Arsenide (GaAs- 904 nm, 4 J/cm2) laser following by irradiation at 24, 48 and 72 hours. Saline injection (0.9% NaCl) was used as control. Gait analysis was performed 24 hours before Bjssu injection and at every period post-Bjssu using CatWalk method. Data from spatiotemporal parameters Stand, Maximum Intensity, Swing, Swing Speed, Stride Length and Step Cycle were considered. The period of 3 hours post venom-induced injury was considered critical for all parameters evaluated in the right hindlimb. Differences (p<0.05) were concentrated in venom and venom + placebo laser groups during the 3 hours post-injury period, in which the values of stand of most animals were null. After this period, the gait characteristics were re established for all parameters. The venom + laser group kept the values at 3 hours post-Bjssu equal to that at 24 hours before Bjssu injection indicating that the GaAs laser therapy improved spatially and temporally gait parameters at the critical injury period caused by Bjssu. This is the first study to analyze with cutting edge technology the gait functional deficits caused by snake envenoming and gait gains produced by GaAs laser irradiation. In this sense, the study fills a gap on the field of motor function after laser treatment following snake envenoming. PMID- 27392015 TI - Regulation of dendritic development by semaphorin 3A through novel intracellular remote signaling. AB - Numerous cell adhesion molecules, extracellular matrix proteins and axon guidance molecules participate in neuronal network formation through local effects at axo dendritic, axo-axonic or dendro-dendritic contact sites. In contrast, neurotrophins and their receptors play crucial roles in neural wiring by sending retrograde signals to remote cell bodies. Semaphorin 3A (Sema3A), a prototype of secreted type 3 semaphorins, is implicated in axon repulsion, dendritic branching and synapse formation via binding protein neuropilin-1 (NRP1) and the signal transducing protein PlexinAs (PlexAs) complex. This review focuses on Sema3A retrograde signaling that regulates dendritic localization of AMPA-type glutamate receptor GluA2 and dendritic patterning. This signaling is elicited by activation of NRP1 in growth cones and is propagated to cell bodies by dynein-dependent retrograde axonal transport of PlexAs. It also requires interaction between PlexAs and a high-affinity receptor for nerve growth factor, toropomyosin receptor kinase A. We propose a control mechanism by which retrograde Sema3A signaling regulates the glutamate receptor localization through trafficking of cis-interacting PlexAs with GluA2 along dendrites; this remote signaling may be an alternative mechanism to local adhesive contacts for neural network formation. PMID- 27392017 TI - Diurnal Changes of Zooplankton Community Reduction Rate at Lake Outlets and Related Environmental Factors. AB - The reduced zooplankton abundance at the outlet sections of lakes depends on the occurrence of preying fry. Therefore, light conditions can play a major role in the drift of zooplankton along river outlets. The aim of this study was to determine the influence of diurnal light conditions on the decline of zooplankton densities at lake outlets. Photosynthetically active radiation (PAR) levels were measured to determine their effect on the rate of reduced zooplankton abundance. Cladocerans and copepods showed a significantly greater reduction in abundance than rotifers and nauplii. A significant positive relationship was observed between the PAR levels and the reduced abundance of Asplanchna sp., small cladocerans, large cladocerans and Copepoda at the lake outlets. Among the rotifers, small pelagic rotifers drifted the farthest at all hours of the day. Large crustaceans, especially the large cladocerans and copepodites and adult copepods, had the lowest chance of dispersing over a wide area. Our results indicate that light conditions play an important role in the reduction of zooplankton abundance at lake outlets and have an indirect influence on the downstream food web. PMID- 27392019 TI - Correction: Simultaneous Induction of Non-Canonical Autophagy and Apoptosis in Cancer Cells by ROS-Dependent ERK and JNK Activation. AB - [This corrects the article DOI: 10.1371/journal.pone.0009996.]. PMID- 27392018 TI - Development and Validation of a Self-Report Measure of Mentalizing: The Reflective Functioning Questionnaire. AB - Reflective functioning or mentalizing is the capacity to interpret both the self and others in terms of internal mental states such as feelings, wishes, goals, desires, and attitudes. This paper is part of a series of papers outlining the development and psychometric features of a new self-report measure, the Reflective Functioning Questionnaire (RFQ), designed to provide an easy to administer self-report measure of mentalizing. We describe the development and initial validation of the RFQ in three studies. Study 1 focuses on the development of the RFQ, its factor structure and construct validity in a sample of patients with Borderline Personality Disorder (BPD) and Eating Disorder (ED) (n = 108) and normal controls (n = 295). Study 2 aims to replicate these findings in a fresh sample of 129 patients with personality disorder and 281 normal controls. Study 3 addresses the relationship between the RFQ, parental reflective functioning and infant attachment status as assessed with the Strange Situation Procedure (SSP) in a sample of 136 community mothers and their infants. In both Study 1 and 2, confirmatory factor analyses yielded two factors assessing Certainty (RFQ_C) and Uncertainty (RFQ_U) about the mental states of self and others. These two factors were relatively distinct, invariant across clinical and non-clinical samples, had satisfactory internal consistency and test-retest stability, and were largely unrelated to demographic features. The scales discriminated between patients and controls, and were significantly and in theoretically predicted ways correlated with measures of empathy, mindfulness and perspective-taking, and with both self-reported and clinician-reported measures of borderline personality features and other indices of maladaptive personality functioning. Furthermore, the RFQ scales were associated with levels of parental reflective functioning, which in turn predicted infant attachment status in the SSP. Overall, this study lends preliminary support for the RFQ as a screening measure of reflective functioning. Further research is needed, however, to investigate in more detail the psychometric qualities of the RFQ. PMID- 27392020 TI - Weekly Fluctuations in Risk Tolerance and Voting Behaviour. AB - Risk tolerance is fundamental to decision-making and behaviour. Here we show that individuals' tolerance of risk follows a weekly cycle. We observed this cycle directly in a behavioural experiment using the Balloon Analogue Risk Task (Lejuez et al., 2002; Study 1). We also observed it indirectly via voting intentions, gathered from 81,564 responses across 70 opinion polls ahead of the Scottish Independence Referendum of 2014 (Study 2) and 149,064 responses across 77 opinion polls ahead of the United Kingdom European Union membership referendum of 2016 (Study 3). In all three studies, risk-tolerance decreased from Monday to Thursday before returning to a higher level on Friday. This pattern is politically significant because UK elections and referendums are traditionally held on a Thursday-the lowest point for risk tolerance. In particular, it raises the possibility that voting outcomes in the UK could be systematically risk-averse. In line with our analysis, the actual proportion of Yes votes in the Scottish Independence Referendum was 4% lower than forecast. Taken together, our findings reveal that the seven-day weekly cycle may have unexpected consequences for human decision-making. They also suggest that the day on which a vote is held could determine its outcome. PMID- 27392021 TI - Intrathyroidal parathyroid adenoma: Diagnostic pitfalls on fine-needle aspiration: Two case reports and literature review. AB - Parathyroid adenomas may occur within the thyroid, clinically simulating thyroid nodules. Fine-needle aspiration (FNA) of these presumably "thyroid nodules" can lead to misinterpretation of cytomorphological findings because of similarities in cytological features of parathyroid and thyroid lesions. Here, we reported two cases of intrathyroidal parathyroid adenomas. One of them was misinterpreted as thyroid lesions. The other was composed exclusively of oncocytic cells and had a correct cytological diagnosis. In this study, both cases showed a new cytological feature which has not been reported in the literature: many capillaries protruding outside the three-dimensional fragments without epithelial cells around. Diagn. Cytopathol. 2016;44:921-925. (c) 2016 Wiley Periodicals, Inc. PMID- 27392022 TI - Experimental Insights into the Cognitive Significance of Early Stone Tools. AB - Stone-flaking technology is the most enduring evidence for the evolving cognitive abilities of our early ancestors. Flake-making was mastered by African hominins ~3.3 ma, followed by the appearance of handaxes ~1.75 ma and complex stone reduction strategies by ~1.6 ma. Handaxes are stones flaked on two opposed faces ('bifacially'), creating a robust, sharp-edged tool, and complex reduction strategies are reflected in strategic prior flaking to prepare or 'predetermine' the nature of a later flake removal that served as a tool blank. These technologies are interpreted as major milestones in hominin evolution that reflect the development of higher-order cognitive abilities, and the presence and nature of these technologies are used to track movements of early hominin species or 'cultures' in the archaeological record. However, the warranting argument that certain variations in stone tool morphologies are caused by differences in cognitive abilities relies on analogy with technical replications by skilled modern stoneworkers, and this raises the possibility that researchers are projecting modern approaches to technical problems onto our non-modern hominin ancestors. Here we present the results of novel experiments that randomise flake removal and disrupt the modern stoneworker's inclination to use higher-order reasoning to guide the stone reduction process. Although our protocols prevented goal-directed replication of stone tool types, the experimental assemblage is morphologically standardised and includes handaxe-like 'protobifaces' and cores with apparently 'predetermined' flake removals. This shows that the geometrical constraints of fracture mechanics can give rise to what appear to be highly designed stoneworking products and techniques when multiple flakes are removed randomly from a stone core. PMID- 27392023 TI - Evaluation of Reference Genes for Reverse Transcription Quantitative PCR Studies of Physiological Responses in the Ghost Moth, Thitarodes armoricanus (Lepidoptera, Hepialidae). AB - Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is the sensitive method to quantify the expression levels of target genes on the basis of endogenous control. An appropriate reference gene set for normalization is essential for reliable results. The ghost moth, Thitarodes armoricanus, a host species of a medicinal fungus, Ophiocordyceps sinensis, is an economically important member of the Lepidoptera. Recent studies have focused on the mechanism of adaptation of this species to its high-altitude environment and host immune response to O. sinensis infection and RT-qPCR is commonly used in these studies to decipher the genetic basis of physiological functions. However, a thorough assessment of candidate reference genes in the genus Thitarodes is lacking. Here, the expression levels of eight candidate reference genes (ACT, EF, EIF4A, GAPDH, G6PDH, RPL13A, TUB and 18S) in T. armoricanus at different developmental stages and in different body parts of the seventh instar larvae were analyzed, along with larvae kept under low temperatures, larvae exposed to two fungal infections and larvae fed different diets. Three established software programs-Bestkeeper, geNorm and NormFinder-were employed to calculate variation among the treatments. The results revealed that the best-suited reference genes differed across the treatments, with EF, EIF4A and GAPDH found to be the best suited for the different developmental stages and larvae body parts; EF, EIF4A and RPL13A found to be the best suited for low-temperature challenge; and EF, EIF4A and TUB found to be the best suited for the fungal infections and dietary treatments. This study thus further contributes to the establishment of an accurate method for normalizing RT-qPCR results for T. armoricanus and serves as a reference for gene expression studies of related insect species. PMID- 27392024 TI - Comparisons of the in-the-bag stabilities of single-piece and three-piece intraocular lenses for age-related cataract patients: a randomized controlled trial. AB - BACKGROUND: To compare the in-the-bag stability and visual function of single piece intraocular lenses (IOLs) and three-piece IOLs. METHODS: A total of 65 patients with age-related cataracts (80 eyes) were enrolled and randomly assigned to receive in-the-bag implantation of either a single-piece IOL (40 eyes) or a three-piece IOL (40 eyes). Follow-up visits were conducted at 1 week, 1 month and 3 months postoperatively. Visual acuity, refraction and total aberration were examined. IOL position stability (including axial movement, decentration and tilt) was measured using a Scheimpflug imaging system. RESULTS: At the 3-month follow-up visit, single-piece IOLs did not exhibit significant axial movement (0.07 +/- 0.30 mm, p = 0.13) compared with their axial position at 1 week postoperatively, whereas three-piece IOLs displayed forward axial movement of 0.22 +/- 0.23 mm (p < 0.0001). The mean manifest spherical equivalence (SE) of eyes with single-piece IOL was 0.15 +/- 0.18D, whereas in eyes with three-piece IOLs, the mean manifest SE was -0.34 +/- 0.15D (p < 0.001). There was no statistically significant difference in IOL decentration, tilt, uncorrected visual acuity, best-corrected visual acuity or total spherical aberration between the two groups. CONCLUSIONS: Three months after implantation, single-piece IOLs exhibit better axial stability and more stable refractive outcome than three piece IOLs, but both IOLs perform equally well in terms of decentration, tilt, visual acuity and total aberration. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02609997 , 11/18/2015, retrospectively registered. PMID- 27392025 TI - Viewing alcohol warning advertising reduces urges to drink in young adults: an online experiment. AB - BACKGROUND: Tobacco counter-advertising is effective at promoting smoking cessation. Few studies have evaluated the impact of alcohol warning advertising on alcohol consumption and possible mechanisms of effect. This pilot study aimed to assess whether alcohol warning advertising is effective in reducing urges to drink alcohol, if emotional responses to advertising explain any such effect or perceived effectiveness, and whether effects differ among heavier drinkers. METHODS: One hundred fifty-two young adult (aged 18-25) alcohol users completed an online experiment in which they were randomly assigned to view one of three sets of six advertisements: (i) alcohol warning; (ii) alcohol promoting; or (iii) advertisements for non-alcohol products. Urges to drink alcohol were self reported post-exposure. Affective responses (pleasure and arousal) to each advertisement and perceived effectiveness of each advertisement were recorded. Typical level of alcohol consumption was measured as a potential effect modifier. RESULTS: Participants exposed to alcohol warning advertisements reported significantly lower urges to drink alcohol than those who viewed either alcohol promoting or non-alcohol advertisements. This effect was fully mediated by negative affective responses (displeasure) to the alcohol warning advertisements. Perceived effectiveness of alcohol warning advertisements was associated with high arousal responses. Impact of the advertisements was unaffected by typical level of alcohol consumption, although the study was not powered to detect anything other than large effects. CONCLUSIONS: In line with findings from the tobacco literature, alcohol warning advertisements that elicit negative affect reduce urges to drink alcohol. Their impact upon actual consumption awaits investigation. PMID- 27392026 TI - Effect of a booster dose of influenza vaccine in patients with hemodialysis, peritoneal dialysis and renal transplant recipients: A systematic literature review and meta-analysis. AB - Booster influenza vaccination has been recommended for patients with chronic renal disease in order to enhance the immune response to the influenza vaccine; however, the efficacy of a booster influenza vaccination is a matter of controversy. Therefore, we made a meta-analysis to determine the efficacy in patients with hemodialysis (HD), peritoneal dialysis (PD) and renal transplant recipient (RT). The sero-protection rate was used as a serologic parameter to describe the immune response to the vaccine. Statistical analysis was performed to calculate the pooled rate difference (RD) and 95% confidence interval (CI). The pooled RD for the H1N1, H3N2 and B influenza vaccines was 0.02 (95% CI: -0.02 0.06), 0.05 (95% CI: -0.01-0.11), 0.04 (95% CI: -0.02-0.10), respectively. We concluded that a booster dose of the influenza vaccine did not effectively enhance immunogenicity. Therefore, a booster dose of vaccine is not recommended for patients with hemodialysis, peritoneal dialysis and renal transplant recipients. PMID- 27392027 TI - Implementation of Child Death Review in the Netherlands: results of a pilot study. AB - BACKGROUND: Child mortality in the Netherlands declined gradually in the past decades. In total 1130 children and youth aged 0 to 19 years died in 2014 (i.e. 29.4 per 100,000 live births). A better understanding of the background and the circumstances surrounding the death of children as well as the manner and cause of death may lead to preventive measures. Child Death Review (CDR) is a method to systematically analyze child deaths by a multidisciplinary team to identify avoidable factors that may have contributed to the death and to give directions for prevention. CDR could be an addition to further reduce avoidable child deaths in the Netherlands. The purpose of this study is to explore the strengths, weaknesses, opportunities and threats (SWOT) of the pilot-implementation of CDR in a Dutch region. The results are translated in recommendations for future implementation of the CDR method in the Netherlands. METHODS: Children who lived in the pilot region and died aged 29 days after birth until 2 years were, after parental consent, included for reviewing by a regional CDR team. Eighteen logs and seven transcribed records of CDR meetings concerning 6 deceased children were analyzed using Atlas ti. The SWOT framework was used to identify important themes. RESULTS: The most important strengths identified were the expertise of and cooperation within the CDR team and the available materials. An important weakness was the poor cooperation of some professional groups. The fact that parents and professionals endorse the objective of CDR was an important opportunity. The lack of statutory basis was a threat. CONCLUSIONS: Many obstacles need to be taken away before large-scale implementation of CDR in the Netherlands becomes possible. The most important precondition for implementation is the acceptance among professionals and the statutory basis of the CDR method. PMID- 27392028 TI - Reversal of galectin-1 gene silencing on resistance to cisplatin in human lung adenocarcinoma A549 cells. AB - This study aims to investigate reversal of Galectin-1 gene silencing on resistance to cisplatin in human lung adenocarcinoma A549 (or A549/DDP) in vivo and in vitro. The stably transfected lentivirus vector was used to silence Galectin-1 in human lung adenocarcinoma cell line A549 and A549/DDP cells and the cell lines were cultured and passaged. RT-PCR and western blot assay were used to test A549, A549/DDP cells, silenced Galectin-1A549 (A549/I) cells, Galectin-1 mRNA and protein expression levels, respectively, in A549/DDP (A549/DDP/I) cells. CCK8 assay was used to measure median inhibitory concentration (IC50) in each group and resistant index of A549/DDP cells and A549/DDP/I cells. Tumor model in nude mice was established by armpit injection of A549, A549/DDP, A549/I, A549/DDP/I cells. Cisplatin was injected intraperitoneally in tumor models and growth of tumor was observed in vivo model. Four weeks later, nude mice were killed and tumor weight and diameter was measured. mRNA and protein expression of Galectin-1 in A549/DDP cells was higher than that in A549 cells. mRNA and protein expression of Galectin-1 in A549/DDP/I cells was lower than that in A549/DDP cells. Moreover, IC50 values and resistance index in A549/DDP cells was higher than that in A549 cells group and IC50 values and resistance index A549/DDP/I cell group were lower than that in A549/DDP cells. Additionally, tumor weight and volume in A549/DDP/I cell group were lower than that in A549/DDP. In conclusion, Galectin-1 gene silencing would improve the sensitivity of A549/DDP cells to cisplatin in vivo and in vitro. PMID- 27392029 TI - CHIP involves in non-small cell lung cancer prognosis through VEGF pathway. AB - AIM: CHIP (c-terminal Hsp70-interacting protein) is an E3 ligase playing vital roles in various cancers. The VEGF pathway has become an important therapeutic target in non-small cell lung cancer (NSCLC). However, little is known about the role of CHIP and the relationship between CHIP and VEGF-VEGFR2 (VEGF receptor 2) pathway in NSCLC. In this study we aimed to investigate the clinical function of CHIP in NSCLC and explore the relevant regulatory mechanism. METHODS: QRT-PCR was performed to detect CHIP expression in NSCLC tissues. The association of CHIP expression and clinical parameters was analyzed using the Chi-square test. Kaplan Meier and Cox analyses were performed to identify the role of CHIP in the prognosis of NSCLC patients. ELISA test was used to detect the VEGF secretion of NSCLC cells and western blot were used to detected the protein expression of VEGFR2 in NSCLC cells. RESULTS: and the results revealed that CHIP expression was decreased in NSCLC tissues and significantly correlated with clinical stages, lymph node metastasis and distant metastasis (P<0.05). Moreover, Kaplan-Meier and Cox regression analyses showed that patients with negative expression of CHIP had a shorter survival time and CHIP could be an independent prognostic biomarker. In addition, ELISA tests showed that CHIP negatively regulated the secretion level of VEGF. Furthermore, western blot assay indicated that the VEGFR2 protein level was reduced after CHIP over-expression. CONCLUSIONS: Taken together, our findings demonstrate for the first time that CHIP may serve as a promising prognostic biomarker for NSCLC patients and it may be involved in NSCLC angiogenesis through regulating VEGF secretion and expression of VEGFR2. PMID- 27392030 TI - Trypanocidal activity of ethanolic extracts of Commiphora swynnertonii Burtt on Trypanosoma congolense. AB - BACKGROUND: African trypanosomosis is the disease caused by extracellular protozoan parasites of the genus Trypanosoma transmitted by tsetse flies. The current study has evaluated the trypanocidal activity of Commiphora swynnertonii extracts on Trypanosoma congolense. METHODS: The effect of ethanolic stem bark and resinous extracts on motility of T. congolense was evaluated by in vitro study at concentrations of 2 mg/ml and 4 mg/ml. Then, trypanocidal activity was evaluated by drug incubation infectivity test using mice at concentrations of 0.4 mg/ml and 2 mg/ml. In both studies negative (without drug) and positive (diminazene diaceturate) controls were used. RESULTS: The in vitro study showed that, ethanolic stem bark extract of C. swynnertonii at concentration of 4 mg/ml caused complete cessation of motility for T. congolense in 30 min. However, resinous ethanolic extract had delayed effect on cessation of motility of T. congolense observed at 90 and 100 min post-incubation at concentrations of 4 mg/ml and 2 mg/ml respectively. The drug incubation infectivity test study depicted that ethanolic stem bark extract at concentration of 2 mg/ml significantly (p = 0.000) reduced the infectivity of T. congolense in mice. However, it did not vary significantly (P =0.897) with group treated with diminazene diaceturate incubated mixture. CONCLUSION: The current study has provided evidence that, ethanolic stem bark extract of C. swynnertonii possess trypanocidal activity against T. congolense. Based on these findings, further studies are recommended to determine its potential as a lead to trypanocidal drug discovery. PMID- 27392031 TI - Imprecise intron losses are less frequent than precise intron losses but are not rare in plants. AB - In this study, we identified 19 intron losses, including 11 precise intron losses (PILs), six imprecise intron losses (IILs), one de-exonization, and one exon deletion in tomato and potato, and 17 IILs in Arabidopsis thaliana. Comparative analysis of related genomes confirmed that all of the IILs have been fixed during evolution. Consistent with previous studies, our results indicate that PILs are a major type of intron loss. However, at least in plants, IILs are unlikely to be as rare as previously reported. REVIEWERS: This article was reviewed by Jun Yu and Zhang Zhang. For complete reviews, see the Reviewers' Reports section. PMID- 27392032 TI - The Fate of Patients with Solitary Pulmonary Nodules: Clinical Management and Radiation Exposure Associated. AB - BACKGROUND: The appropriate management of the large number of lung nodules detected during the course of routine medical care presents a challenge. We aimed to evaluate the usual clinical practice in solitary pulmonary nodule (SPN) management and associated radiation exposure. METHODS: We examined 893 radiology reports of consecutive patients undergoing chest computed tomography (CT) and radiography at two public hospitals in Spain. Information on diagnostic procedures from SPN detection and lung cancer diagnosis was collected prospectively for 18 months. RESULTS: More than 20% of patients with SPN detected on either chest radiograph (19.8%) or CT (26.1%) underwent no additional interventions and none developed lung cancer (100% negative predictive value). 346 (72.0%) patients with SPN detected on chest radiograph and 254 (61.5%) patients with SPN detected on CT had additional diagnostic tests and were not diagnosed with lung cancer. In patients undergoing follow-up imaging for SPNs detected on CT median number of additional imaging tests was 3.5 and the mean cumulative effective dose was 24.4 mSv; for those detected on chest radiograph the median number of additional imaging tests was 2.8 and the mean cumulative effective dose was 10.3 mSv. CONCLUSIONS: Patients who did not have additional interventions were not diagnosed of lung cancer. There was an excessive amount of interventions in a high percentage of patients presenting SPN, which was associated with an excess of radiation exposure. PMID- 27392033 TI - Facial manifestations of Epstein-Barr virus-related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations. AB - Epstein-Barr virus-related lymphoproliferative disease (EBV-LPD) rarely occurs in patients with acute lymphoblastic leukemia (ALL), who have not received hematopoietic transplantation. We describe EBV-LPD manifesting as facial lesions in two children with ALL in remission. One patient was a 16-year-old male with T cell ALL with an EBV-positive angiocentric polymorphous lip lesion presenting as right-sided facial swelling. The other patient was a 12-year-old male with B-cell ALL with an EBV-positive polymorphous lymphoplasmacytic infiltrate presenting as bilateral dacryoadenitis. Neither patient had known primary immunodeficiencies. Both cases improved with immunosuppressant de-escalation. These cases suggest that immunosuppression induced by maintenance chemotherapy is sufficient to promote EBV-LPD. PMID- 27392034 TI - An Indirect Defence Trait Mediated through Egg-Induced Maize Volatiles from Neighbouring Plants. AB - Attack of plants by herbivorous arthropods may result in considerable changes to the plant's chemical phenotype with respect to emission of herbivore-induced plant volatiles (HIPVs). These HIPVs have been shown to act as repellents to the attacking insects as well as attractants for the insects antagonistic to these herbivores. Plants can also respond to HIPV signals from other plants that warn them of impending attack. Recent investigations have shown that certain maize varieties are able to emit volatiles following stemborer egg deposition. These volatiles attract the herbivore's parasitoids and directly deter further oviposition. However, it was not known whether these oviposition-induced maize (Zea mays, L.) volatiles can mediate chemical phenotypic changes in neighbouring unattacked maize plants. Therefore, this study sought to investigate the effect of oviposition-induced maize volatiles on intact neighbouring maize plants in 'Nyamula', a landrace known to respond to oviposition, and a standard commercial hybrid, HB515, that did not. Headspace volatile samples were collected from maize plants exposed to Chilo partellus (Swinhoe) (Lepidoptera: Crambidae) egg deposition and unoviposited neighbouring plants as well as from control plants kept away from the volatile emitting ones. Behavioural bioassays were carried out in a four-arm olfactometer using egg (Trichogramma bournieri Pintureau & Babault (Hymenoptera: Trichogrammatidae)) and larval (Cotesia sesamiae Cameron (Hymenoptera: Braconidae)) parasitoids. Coupled Gas Chromatography-Mass Spectrometry (GC-MS) was used for volatile analysis. For the 'Nyamula' landrace, GC-MS analysis revealed HIPV production not only in the oviposited plants but also in neighbouring plants not exposed to insect eggs. Higher amounts of EAG active biogenic volatiles such as (E)-4,8-dimethyl-1,3,7-nonatriene were emitted from these plants compared to control plants. Subsequent behavioural assays with female T. bournieri and C. sesamiae parasitic wasps indicated that these parasitoids preferred volatiles from oviposited and neighbouring landrace plants compared to those from the control plants. This effect was absent in the standard commercial hybrid we tested. There was no HIPV induction and no difference in parasitoid attraction in neighbouring and control hybrid maize plants. These results show plant-plant signalling: 'Nyamula' maize plants emitting oviposition induced volatiles attractive to the herbivore's natural enemies can induce this indirect defence trait in conspecific neighbouring undamaged maize plants. Maize plants growing in a field may thus benefit from this indirect defence through airborne signalling which may enhance the fitness of the volatile-emitting plant by increasing predation pressure on herbivores. PMID- 27392035 TI - Maternal outcomes of term breech presentation delivery: impact of successful external cephalic version in a nationwide sample of delivery admissions in the United States. AB - BACKGROUND: We aimed to define the frequency and predictors of successful external cephalic version in a nationally-representative cohort of women with breech presentations and to compare maternal outcomes associated with successful external cephalic version versus persistent breech presentation. METHODS: Using the Nationwide Inpatient Sample, a United States healthcare utilization database, we identified delivery admissions between 1998 and 2011 for women who had successful external cephalic version or persistent breech presentation (including unsuccessful or no external cephalic version attempt) at term. Multivariable logistic regression identified patient and hospital-level factors associated with successful external cephalic version. Maternal outcomes were compared between women who had successful external cephalic version versus persistent breech. RESULTS: Our study cohort comprised 1,079,576 delivery admissions with breech presentation; 56,409 (5.2 %) women underwent successful external cephalic version and 1,023,167 (94.8 %) women had persistent breech presentation at the time of delivery. The rate of cesarean delivery was lower among women who had successful external cephalic version compared to those with persistent breech (20.2 % vs. 94.9 %; p < 0.001). Compared to women with persistent breech at the time of delivery, women with successful external cephalic version were also less likely to experience several measures of significant maternal morbidity including endometritis (adjusted Odds Ratio (aOR) = 0.36, 95 % Confidence Interval (CI) 0.24-0.52), sepsis (aOR = 0.35, 95 % CI 0.24-0.51) and length of stay > 7 days (aOR = 0.53, 95 % CI 0.40-0.70), but had a higher risk of chorioamnionitis (aOR = 1.83, 95 % CI 1.54-2.17). CONCLUSIONS: Overall a low proportion of women with breech presentation undergo successful external cephalic version, and it is associated with significant reduction in the frequency of cesarean delivery and a number of measures of maternal morbidity. Increased external cephalic version use may be an important approach to mitigate the high rate of cesarean delivery observed in the United States. PMID- 27392036 TI - Four Reasons to Question the Accuracy of a Biotic Index; the Risk of Metric Bias and the Scope to Improve Accuracy. AB - Natural ecological variability and analytical design can bias the derived value of a biotic index through the variable influence of indicator body-size, abundance, richness, and ascribed tolerance scores. Descriptive statistics highlight this risk for 26 aquatic indicator systems; detailed analysis is provided for contrasting weighted-average indices applying the example of the BMWP, which has the best supporting data. Differences in body size between taxa from respective tolerance classes is a common feature of indicator systems; in some it represents a trend ranging from comparatively small pollution tolerant to larger intolerant organisms. Under this scenario, the propensity to collect a greater proportion of smaller organisms is associated with negative bias however, positive bias may occur when equipment (e.g. mesh-size) selectively samples larger organisms. Biotic indices are often derived from systems where indicator taxa are unevenly distributed along the gradient of tolerance classes. Such skews in indicator richness can distort index values in the direction of taxonomically rich indicator classes with the subsequent degree of bias related to the treatment of abundance data. The misclassification of indicator taxa causes bias that varies with the magnitude of the misclassification, the relative abundance of misclassified taxa and the treatment of abundance data. These artifacts of assessment design can compromise the ability to monitor biological quality. The statistical treatment of abundance data and the manipulation of indicator assignment and class richness can be used to improve index accuracy. While advances in methods of data collection (i.e. DNA barcoding) may facilitate improvement, the scope to reduce systematic bias is ultimately limited to a strategy of optimal compromise. The shortfall in accuracy must be addressed by statistical pragmatism. At any particular site, the net bias is a probabilistic function of the sample data, resulting in an error variance around an average deviation. Following standardized protocols and assigning precise reference conditions, the error variance of their comparative ratio (test-site:reference) can be measured and used to estimate the accuracy of the resultant assessment. PMID- 27392037 TI - Crimean-Congo hemorrhagic fever virus in livestock ticks and animal handler seroprevalence at an abattoir in Ghana. AB - BACKGROUND: Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is a zoonotic virus transmitted by Ixodid ticks and causes Crimean-Congo hemorrhagic fever (CCHF) disease in humans with up to 50 % mortality rate. METHODS: Freshly slaughtered livestock at the Kumasi abattoir in the Ashanti Region of Ghana were examined for the presence of ticks once a month over a 6-month period from May to November 2011. The ticks were grouped into pools by species, sex, and animal source. CCHFV was detected in the ticks using reverse transcription PCR. Blood samples were collected from enrolled abattoir workers at initiation, and from those who reported fever in a preceding 30-day period during monthly visits 2-5 months after initiation. Six months after initiation, all participants who provided baseline samples were invited to provide blood samples. Serology was performed using enzyme linked immunosorbent assay (ELISA). Demographic and epidemiological data was also obtained from enrolled participants using a structured questionnaire. RESULTS: Of 428 freshly slaughtered animals comprising 130 sheep, 149 cattle, and 149 goats examined, 144 ticks belonging to the genera Ambylomma, Hyalomma and Boophilus were identified from 57 (13.3 %): 52 (34.9 %), 4 (3.1 %) and 1 (0.7 %) cattle, sheep and goat respectively. Of 97 tick pools tested, 5 pools comprising 1 pool of Hyalomma excavatum and 4 pools of Ambylomma variegatum, collected from cattle, were positive for CCHFV. Of 188 human serum samples collected from 108 abattoir workers, 7 (3.7 %) samples from 6 persons were anti-CCHF IgG positive with one of them also being CCHF IgM positive. The seroprevalence of CCHFV identified in this study was 5.7 %. CONCLUSIONS: This study detected human exposure to CCHF virus in slaughterhouse workers and also identified the CCHF virus in proven vectors (ticks) of Crimean Congo hemorrhagic fever in Ghana. The CCHFV was detected only in ticks collected from cattle, one of the livestock known to play a role in the amplification of the CCHF virus. PMID- 27392038 TI - Benzodiazepine-refractory status epilepticus: pathophysiology and principles of treatment. AB - Cholinergic status epilepticus (CSE) quickly becomes self-sustaining, independent of its initial trigger, and resistant to benzodiazepines and other antiepileptic drugs. We review a few of the many physiological changes associated with CSE, with an emphasis on receptor trafficking. Time-dependent internalization of synaptic gamma-aminobutyric acid (GABA)A receptors explains, in part, the loss of inhibition and the loss of response to benzodiazepines in the early stages of CSE. The increase in N-methyl-d-aspartate receptors may contribute to the runaway excitation and excitotoxicity of CSE. These changes have therapeutic implications. The time-dependent increase in maladaptive changes points to the importance of early treatment. The involvement of both inhibitory and excitatory systems challenges current therapeutic guidelines, which recommend treating only one system, and questions the rationale for monotherapy. It suggests that polytherapy may be needed, especially when treatment is delayed, so that drugs can only reach a much reduced number of GABAA receptors. Finally, it raises the possibility that the current practice of waiting for one treatment to fail before starting the next drug may need to be reevaluated. PMID- 27392039 TI - Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration. AB - Repurposing the macrolide antibiotic azithromycin has recently been suggested as a promising neuroprotective strategy for the acute treatment of ischemic stroke. Here, we aim at further characterizing the immunomodulatory properties of intraperitoneal (i.p.) administration of this drug and, more importantly, at assessing whether neuroprotection can also be achieved by the more clinically relevant intravenous (i.v.) route of administration in a mouse model of focal cerebral ischemia induced by transient (30-min) middle cerebral artery occlusion (MCAo). A single i.p. injection of azithromycin (150 mg/kg) upon reperfusion prevented ischemia-induced spleen contraction and increased the number of MAC-1 immunopositive microglia/macrophages in the ischemic hemisphere 48 h after the insult. This was paralleled by an elevation of alternatively activated phenotypes (i.e., Ym1-immunopositive M2-polarized cells) and by a reduced expression of the pro-inflammatory marker myeloperoxidase. More importantly, i.v. administration of azithromycin upon reperfusion reduced MCAo-induced infarct volume and cerebral edema to an extent comparable to that obtained via the i.p. route. Although the i.p. route is often used for research purposes, it is impractical in the clinical setting; however, i.v. administration can easily be used in ischemic stroke patients who usually have i.v. access already established on hospital admission. The neuroprotective efficacy of the clinically relevant i.v. administration of azithromycin, together with its beneficial immunomodulatory properties reported in mice subjected to transient MCAo, suggests that this macrolide antibiotic can be effectively repurposed for the acute treatment of ischemic stroke. To this end, further work is needed to validate the efficacy of azithromycin in the clinical setting. PMID- 27392041 TI - Grasping in One-Handed Catching in Relation to Performance. AB - Catching a flying ball involves bringing the hand to the aimed interception point at the right time, adjusting the hand posture to receive the incoming ball and to absorb the ball momentum, and closing the hand to ensure a stable grip. A small error in any of these actions can lead to a failure in catching the ball. Here we sought to gather new insights on what aspects of the catching movements affect the interceptive performance most. In particular, we wondered whether the errors occurred in bringing the hand to the interception point or in closing the fingers on the ball, and whether these two phases of interception differed between individuals. To this end, we characterized grasping and wrist movement kinematics of eleven participants attempting to catch a ball projected in space with different ball arrival heights and flight durations. The spatial position of the ball and of several markers placed on the participant's arm were recorded by a motion capture system, the hand joint angles were recorded with an instrumented glove, and several movement features were extracted. All participants were able to intercept the ball trajectory (i.e. to touch the ball) in over 90% of cases, but they differed in the ability to grasp the ball (success rate varied between 2% and 85%). Similar temporal features were observed across individuals when they caught the ball. In particular, all participants adapted their wrist movements under varying temporal and arrival height constraints, they aligned the time of peak hand closing velocity to the time of hand-ball contact, and they maintained the same hand closing duration in the different experimental conditions. These movement features characterized successful trials, and hence allowed to evaluate the possible sources of errors underlying unsuccessful trials. Thus, inter individual and inter-trial variability in the modulation of each kinematic feature were related to catching performance. We observed that different participants used different solutions to bring the hand to the interception point. In particular the value of the wrist velocity at impact distinguished good from poor catchers. However, each individual showed similar wrist kinematics in grasped and touched trials. We also found that specific grasping features predicted the catching outcome, both on a trial-by-trial basis and across individuals of different performance level. A higher speed of hand closing distinguished touched from grasped trials. A proper triggering of the enclosing phase of the grasping movement and an accurate alignment of the peak of the hand closing speed to the impact event predicted the catching performance of different participants. These results indicate that the control of the grasping movement was the main source of errors affecting catching performance in our experiments. Moreover, these results suggest that distinct temporal and spatial features in the coordination of the grasping movement are related to individual catching abilities. PMID- 27392040 TI - Is Nigeria winning the battle against malaria? Prevalence, risk factors and KAP assessment among Hausa communities in Kano State. AB - BACKGROUND: Malaria is one of the most severe global public health problems worldwide, particularly in Africa, where Nigeria has the greatest number of malaria cases. This community-based study was designed to investigate the prevalence and risk factors of malaria and to evaluate the knowledge, attitudes, and practices (KAP) regarding malaria among rural Hausa communities in Kano State, Nigeria. METHODS: A cross-sectional community-based study was conducted on 551 participants from five local government areas in Kano State. Blood samples were collected and examined for the presence of Plasmodium species by rapid diagnostic test (RDT), Giemsa-stained thin and thick blood films, and PCR. Moreover, demographic, socioeconomic, and environmental information as well as KAP data were collected using a pre-tested questionnaire. RESULTS: A total of 334 (60.6 %) participants were found positive for Plasmodium falciparum. The prevalence differed significantly by age group (p < 0.01), but not by gender or location. A multivariate analysis showed that malaria was associated significantly with being aged 12 years or older, having a low household family income, not using insecticide treated nets (ITNs), and having no toilets in the house. Overall, 95.6 % of the respondents had prior knowledge about malaria, and 79.7, 87.6 and 95.7 % of them knew about the transmission, symptoms, and prevention of malaria, respectively. The majority (93.4 %) of the respondents considered malaria a serious disease. Although 79.5 % of the respondents had at least one ITN in their household, utilization rate of ITNs was 49.5 %. Significant associations between the respondents' knowledge concerning malaria and their age, gender, education, and household monthly income were reported. CONCLUSIONS: Malaria is still highly prevalent among rural Hausa communities in Nigeria. Despite high levels of knowledge and attitudes in the study area, significant gaps persist in appropriate preventive practices, particularly the use of ITNs. Innovative and Integrated control measures to reduce the burden of malaria should be identified and implemented in these communities. Community mobilization and health education regarding the importance of using ITNs to prevent malaria and save lives should be considered. PMID- 27392043 TI - Deformylation Reaction by a Nonheme Manganese(III)-Peroxo Complex via Initial Hydrogen-Atom Abstraction. AB - Metal-peroxo intermediates are key species in the catalytic cycles of nonheme metalloenzymes, but their chemical properties and reactivity patterns are still poorly understood. The synthesis and characterization of a manganese(III)-peroxo complex with a pentadentate bispidine ligand system and its reactivity with aldehydes was studied. Manganese(III)-peroxo can react through hydrogen-atom abstraction reactions instead of the commonly proposed nucleophilic addition reaction. Evidence of the mechanism comes from experiments which identify a primary kinetic isotope effect of 5.4 for the deformylation reaction. Computational modeling supports the established mechanism and identifies the origin of the reactivity preference of hydrogen-atom abstraction over nucleophilic addition. PMID- 27392042 TI - Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion. AB - The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID- 27392044 TI - Rethinking the assessment of risk of bias due to selective reporting: a cross sectional study. AB - BACKGROUND: Selective reporting is included as a core domain of Cochrane's tool for assessing risk of bias in randomised trials. There has been no evaluation of review authors' use of this domain. We aimed to evaluate assessments of selective reporting in a cross-section of Cochrane reviews and to outline areas for improvement. METHODS: We obtained data on selective reporting judgements for 8434 studies included in 586 Cochrane reviews published from issue 1-8, 2015. One author classified the reasons for judgements of high risk of selective reporting bias. We randomly selected 100 reviews with at least one trial rated at high risk of outcome non-reporting bias (non-/partial reporting of an outcome on the basis of its results). One author recorded whether the authors of these reviews incorporated the selective reporting assessment when interpreting results. RESULTS: Of the 8434 studies, 1055 (13 %) were rated at high risk of bias on the selective reporting domain. The most common reason was concern about outcome non reporting bias. Few studies were rated at high risk because of concerns about bias in selection of the reported result (e.g. reporting of only a subset of measurements, analysis methods or subsets of the data that were pre-specified). Review authors often specified in the risk of bias tables the study outcomes that were not reported (84 % of studies) but less frequently specified the outcomes that were partially reported (61 % of studies). At least one study was rated at high risk of outcome non-reporting bias in 31 % of reviews. In the random sample of these reviews, only 30 % incorporated this information when interpreting results, by acknowledging that the synthesis of an outcome was missing data that were not/partially reported. CONCLUSIONS: Our audit of user practice in Cochrane reviews suggests that the assessment of selective reporting in the current risk of bias tool does not work well. It is not always clear which outcomes were selectively reported or what the corresponding risk of bias is in the synthesis with missing outcome data. New tools that will make it easier for reviewers to convey this information are being developed. PMID- 27392045 TI - Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease. AB - BACKGROUND: The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. AIM: To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. METHODS: Double-blind randomized clinical trial of gluten vs placebo rechallenge. INCLUSION CRITERIA: >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated. RESULTS: 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable 'coeliac lite' disease. CONCLUSION: This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten free diet. TRIAL REGISTRATION: ClinicalTrials.gov NCT02472704. PMID- 27392046 TI - A Robust Speaker Identification System Using the Responses from a Model of the Auditory Periphery. AB - Speaker identification under noisy conditions is one of the challenging topics in the field of speech processing applications. Motivated by the fact that the neural responses are robust against noise, this paper proposes a new speaker identification system using 2-D neurograms constructed from the responses of a physiologically-based computational model of the auditory periphery. The responses of auditory-nerve fibers for a wide range of characteristic frequency were simulated to speech signals to construct neurograms. The neurogram coefficients were trained using the well-known Gaussian mixture model-universal background model classification technique to generate an identity model for each speaker. In this study, three text-independent and one text-dependent speaker databases were employed to test the identification performance of the proposed method. Also, the robustness of the proposed method was investigated using speech signals distorted by three types of noise such as the white Gaussian, pink, and street noises with different signal-to-noise ratios. The identification results of the proposed neural-response-based method were compared to the performances of the traditional speaker identification methods using features such as the Mel frequency cepstral coefficients, Gamma-tone frequency cepstral coefficients and frequency domain linear prediction. Although the classification accuracy achieved by the proposed method was comparable to the performance of those traditional techniques in quiet, the new feature was found to provide lower error rates of classification under noisy environments. PMID- 27392047 TI - [Not Available]. PMID- 27392048 TI - [Nutrition education in schools: potential resources for a teacher/nurse partnership]. AB - CONTEXT: Nutrition education in schools must be based on a collaborative approach between teachers and school nurses. The objective of this study was to compare the nutrition education representations and practices of primary school teachers and school nurses in the Languedoc-Roussillon region in the South of France. We used the theoretical framework of complexity, which is particularly suited to multifactorial phenomena such as nutrition education. METHODS: We interviewed 112 primary school teachers and 33 school nurses about three aspects of their nutrition education representations and practices: actors, content and place of nutrition education at school. RESULTS: Nurses had a more comprehensive and complex approach to nutrition education, including a collaborative approach. However, teachers had a fairly simplistic view of nutrition education and their practice took little account of the psychosocial dimensions of nutrition and a collaborative approach. CONCLUSION: Nurses could be resources for teachers to help them change their approach to health by transforming a purely biomedical approach to health and nutrition into a more comprehensive approach, particularly taking into account in its psychological and social dimensions, which would be more appropriate to address the growing prevalence of diet-related chronic diseases in France today. PMID- 27392049 TI - [COMETE: a tool to develop psychosocial competences in patient education]. AB - This article presents a detailed description of the development and use of the COMETE tool. The COMETE tool is designed to help medical teams identify, develop or evaluate psychosocial skills in patient education and counselling. This tool, designed in the form of a briefcase, proposes methodological activities and cards that assess psychosocial skills during a shared educational assessment, group meetings or during an individual evaluation. This tool is part of a support approach for medical teams caring for patients with chronic diseases. PMID- 27392050 TI - [First-aid training at work on interpersonal development: exploratory study on employees in integration into the workplace centres]. AB - The National Institute of Research and Security and the "CHANTIER Ecole" network have developed first-aid training for employees of integration into the workplace centres. Specifically geared towards workplace safety, but similar in its content to home first-aid and rescue training, this training is also designed to enhance individual and collective responsibility and citizenship. The purpose of this study was to evaluate the personal and interpersonal effects of first-aid training of these employees by considering their social and professional difficulties in terms of psychosocial skills, such as empowerment, stress and emotions management, and decision-making capacity. A descriptive-inductive study was conducted over 18 months based on the grounded theory approach. Five integration into the work-place centres participated in the study and 34 interviews were conducted. These results raise several questions concerning: a) the characteristics of this public targeted by this training and their perception of integration into the workplace; b) the suitability of this training to working conditions and the link with other types of training such as family health education; c) the relationship between citizenship training and first-aid training at work, as it is more applicable to family training than workplace training. A quantitative study is considered to confirm these observations in other integration into the workplace centres. PMID- 27392051 TI - [Construction of health and social inequalities in health: genes versus social determinants?]. AB - The cover of a recent issue of Science et Sante, the INSERM magazine, asked the following question concerning epigenetics: "What is the exact role played by the genome?". Strangely, the first page of this same issue raised another question: "How to fight health inequalities?". We will try to answer these two questions and determine the links between them by examining public health challenges and the questions raised by recent progress in biology, especially epigenetics. The results of this analysis support those of epidemiological studies highlighting the importance of examining the construction of health during life. These studies may throw new light on the issue of social inequalities in health and how to reduce these inequalities. PMID- 27392052 TI - [70 years of school health in France: an old lady’s forgotten birthday]. AB - School health in France has recently celebrated its 70th birthday. The authors review the last 70 years and the adjustments made by the various professionals in this field to adapt to political and institutional changes, whether or not these changes were designed to improve the health of infants and children. Changing governance does not facilitate the essential place of team work, especially between Ministry of Education doctors, nurses and social workers. Although these professionals regret the lack of publicity concerning the 70 years of school health, the continuing commitment of young school health professionals illustrates the real importance of health measures in school children and adolescents. PMID- 27392053 TI - [Do general practitioners in Geneva (Switzerland) and Poitou-Charentes (France) have different approach to the management of addictions?]. AB - BACKGROUND: Addiction care is mostly provided by general practitioners (GPs) but the extent of their involvement is variable. Is this related to different training or practice contexts or to awareness campaigns? OBJECTIVE: To study GPs' views and behaviours in relation to addiction patients in different practice and training contexts and different levels of exposure to awareness campaigns. METHODS: Cross-sectional postal survey involving 526 GPs from the canton of Geneva, Switzerland, sensitized by specific addiction care campaigns, compared to 628 GPs from two rural Departments of Poitou-Charentes, France, not exposed to this type of awareness campaign. RESULTS: The response rate was 46% in Switzerland and 41% in France. The 243 responding GPs in Geneva saw as many patients with tobacco, alcohol, cannabis or opiate addiction as the 256 GPs in Poitou-Charentes. They shared similar views concerning their roles in relation to these addictions. Compared to Swiss GPs, a significantly higher number of French GPs provided first-line care for tobacco addiction. In both countries, care for addiction to other substances was mostly provided in collaboration with a specialist (>75% of cases). GPs in Geneva attributed greater importance to screening and recording of substance use. They were also more involved in training and in providing brief advice and expressed interest in the network. CONCLUSION: Awareness campaigns in Geneva could explain these differences. Sensitization of GPs to these issues may contribute to modifying certain professional attitudes, regardless of the context. PMID- 27392054 TI - [Musculoskeletal disorders: Role of medical advisers and inter-professional relations]. AB - INTRODUCTION: Musculoskeletal disorders (MSD) were responsible for 9.7 million days of sick leave in 2010 in France. They are also a leading cause of occupational exclusion. The objective was to study the role of medical advisers (Mas) in the care of patients with MSD and their interactions with general practitioners (GPs) and occupational health physicians (OPs). METHODS: We performed a qualitative study with semi-structured interviews with medical advisers from the Brittany region. Semistructured interviews were double-coded and were submitted to thematic analysis. RESULTS: Nine interviews were conducted with MAs from the general regime, agricultural regime, and independent workers regime. MAs described an increase in MSD, especially with complex forms. They explained that their activity was not limited to control, but that they also had an important role in limiting occupational exclusion. It is important to anticipate difficulties related to return to work in this setting. They reported contrasted but necessary relations with GPs who are at the centre of care. Return to work may require negotiation with OPs. CONCLUSION: Relations between MAs and GPs are partly based on control of prescriptions, which can create a climate of suspicion. Emphasizing the fight against occupational exclusion can provide new light on the role of MAs. Improving relations between MAs and GPs can be achieved by a better understanding of their respective roles. PMID- 27392055 TI - [What is the place of a geriatric follow-up ambulatory care unit in the structures developed by the 2008/2012 Alzheimer Plan?]. AB - The French 2008/2012 Alzheimer Plan is designed to improve the support given to elderly patients and their families. Objective: To describe the typology of the patients managed in a Geriatric multidimensional rehabilitation ambulatory care unit between 2008 and 2012. METHODS: Programme de medicalisation des systemes d'information database concerning the number of concomitant diseases and several specific indicators. RESULTS: The number of patients increased between 2008 (109) and 2009 (293) but then remained stable (about 300). The differences between 2008 and subsequent years were statically significant for the number of concomitant diseases (p < 0.001) and the number of days/patients (p < 0.01), but not for 2009 2012. CONCLUSION: The variations seem to be related to implementation of the Alzheimer Plan and a change in the organization of French gerontology health networks. PMID- 27392057 TI - [A theoretical analysis of coordination in the field of health care: application to coordinated care systems]. AB - Various organizational, functional or structural issues have led to a review of the foundations of the former health care system based on a traditional market segmentation between general practice and hospital medicine, and between health and social sectors and marked by competition between private and public sectors. The current reconfiguration of the health care system has resulted in "new" levers explained by the development of a new organizational reconfiguration of the primary health care model. Coordinated care structures (SSC) have been developed in this context by making coordination the cornerstone of relations between professionals to ensure global, continuous and quality health care. This article highlights the contributions of various theoretical approaches to the understanding of the concept of coordination in the analysis of the current specificity of health care. PMID- 27392056 TI - [Qualitative survey of deaf patients concerning perception of their management by general practitioners]. AB - INTRODUCTION: Doctor-patient communication issues affect general practice consultations of deaf patients. The purpose of this study was to obtain the opinions of deaf patients on the care provided by general practitioners and their expectations in order to suggest possible improvements. METHODS: Qualitative research based on semi-structured interviews with ten deaf patients who use sign language and who mostly consult private general practitioners. RESULTS: Difficulties were encountered to establish a good quality dialogue between deaf patients and general practitioners. Limited exchanges prevent patients and practitioners from creating a relationship based on trust, without bringing the physicians' skills into question. Problems tended to wane over time and depend on the practitioner's awareness of deaf issues. Deaf patients want to receive care in their own language by means of sign language interpreters or by consulting practitioners who use sign language in a Deaf Patient Reception and Care Unit. They also expect their GP to be able to devote more time to them and to more clearly understand the characteristics of their disability in order to improve their health care. CONCLUSION: Although general practitioners' skills are not called into question, the doctor-patient relationship is impaired by communication issues, which have a negative impact on deaf patients' care. This could be improved by strengthening deaf patients' information via public health campaigns, by creating a specific fee in the French medical fee classification related to medical procedures on patients with a sensory disability and by developing tools to facilitate medical consultation. PMID- 27392058 TI - [Infant feeding practices in Nouakchott: between medical guidelines and grandmothers’ instructions]. AB - The World Health Organization recommends exclusive breastfeeding up to the age of six months and continuation of partial breastfeeding up to the age of two years, in addition to nutritionally adequate and safe food. In Mauritania, despite some progress, most mothers do not comply with these recommendations. The aim of this study, conducted in Nouakchott, was to evaluate breastfeeding and feeding practices, and measure factors associated with achievement of the optimal duration of exclusive breastfeeding. The methodology combined quantitative and qualitative approaches. A descriptive cross-sectional study was conducted by questionnaires among 330 mothers from different departments of the capital. Twenty semi-structured interviews were then conducted with Mauritanian grandmothers in order to understand their roles and perceptions about infant feeding. Before the age of 6 months, the exclusive breastfeeding rate was 18.4%, the predominant breastfeeding rate was 44.3% and the partial breastfeeding with milk rate was 28.1%. In addition, 9.2% of infants received supplementary feeding. We found that 50.5% of mothers were aware of the optimal duration of exclusive breastfeeding, but only 14.2% complied with this recommendation. The factors significantly associated with compliance with the optimal duration of exclusive breastfeeding were maternal age over 35 years and multiparity. Interviews revealed that grandmothers knew about some of the nutritional recommendations, but denied their relevance based on their experience. Their advice contradicted certain medical recommendations. Our study revealed inadequacies concerning the mother's knowledge and more frequently their practices in terms of infant feeding. The gap between knowledge and practice can be essentially explained by the relative importance attributed to recommendations by the mothers, as well as the confrontation between medical recommendations and grandmothers' traditional knowledge. PMID- 27392059 TI - [Oral hygiene in Moroccan school children and their mothers]. AB - OBJECTIVE: Parents play an important role in improving children's oral plaque control. The aim of this study was therefore to compare the oral hygiene of children and their mothers and to study the relationship with their oral health status. MATERIALS AND METHODS: Information was collected on oral hygiene habits (brushing, frequency and duration, equipment and methodology, frequency of changing toothbrushes) and various indices (CAF, plaque, bleeding). RESULTS: The sample was composed of 200 children and 200 mothers. The results of this study showed no statistically significant difference between mothers and their children in terms of the method of brushing and the frequency of changing toothbrushes. A statistically significant difference was found between mothers and their children concerning the use and change of toothbrushes and brushing frequency. A highly significant positive correlation was observed between the plaque index of mothers and their children. CONCLUSION: Low rates of toothbrush use were observed in this population and the brushing method was very inefficient. The correlation between the plaque index of mothers and their children suggests that mother's oral hygiene behaviours influence their children's oral health. PMID- 27392060 TI - [Prevalence of nosocomial infections in two hospitals in Conakry (Guinea)]. AB - INTRODUCTION: Nosocomial infections can be prevented by applying simple hygiene rules. However, they have not been sufficiently studied in the Republic of Guinea. For this purpose, we conducted a one-day study in the Conakry University Hospital surgery wards and intensive care units. METHODS: Fourteen units (12 surgical wards and 2 intensive care units) participated in the study. RESULTS: A total of 310 patients were included. A nosocomial infection was observed in 62 patients, [20%, 95%CI 15.9-24.8%]. Surgical site infections were significantly more frequent with 42/62 cases [67.7%, 95%CI 55.3-78.1%, p = 0.0001] than other types of infections (urinary tract, skin and digestive) with 20/62 cases [32.3% 95%CI 21.9-44.6%]. The average hospital stay of 29.1 +/- 23.4 days [95%CI, 23.2 +/- 35.04] for patients with nosocomial infection was significantly different (p = 0.0001) from that observed in patients without nosocomial infection: 15.9 +/- 16.3 days [95%CI, 13.8 +/- 17.9]. Staphylococcus aureus was the pathogen most commonly isolated: 32/62 (51.6%; 95%CI 39.5-63.6%). Escherichia coli infection was identified in the bladder catheters of 13 patients [20.9%, 95%CI 12.7-32.6%]. Finally, five deaths were observed among the 62 patients with nosocomial infection. DISCUSSION: This study shows that nosocomial infections are common in Conakry University Hospital. Further studies must be conducted to identify the risk factors for nosocomial infections and to propose solutions. PMID- 27392061 TI - [Oral health status, supply of oral and dental care among Senegalese children: a review of available data]. AB - INTRODUCTION: Oral and dental diseases are a major public health problem due to their high prevalence and their impact on general health. OBJECTIVE: This article reviews the oral health status and oral health care supply and uptake in children. METHOD: The available literature were reviewed. The Medline and Embase databases, and the Senegal Ministry of Health and Social Action and National Agency of Statistics and Demography (ANSD) websites were consulted. A total of 7 articles, 3 PhD theses and 8 reports were selected for analysis. The review was supplemented by interviews. RESULTS: Overall, children have poor oral health status. Health care supply is insufficient (1 dentist/38,000 residents) and poorly distributed (mostly in the capital) with unequal oral health care uptake. CONCLUSION: This systematic review of the literature revealed a lack of reliable data on the oral health of children. It also concluded on a generally poor oral health status. PMID- 27392063 TI - Identification, Functional Characterization and Regulon Prediction of a Novel Two Component System Comprising BAS0540-BAS0541 of Bacillus anthracis. AB - Two component systems (TCSs) can be envisaged as complex molecular devices that help the bacteria to sense its environment and respond aptly. 41 TCSs are predicted in Bacillus anthracis, a potential bioterrorism agent, of which only four have been studied so far. Thus, the intricate signaling network contributed by TCSs remains largely unmapped in B. anthracis and needs comprehensive exploration. In this study, we functionally characterized one such system composed of BAS0540 (Response regulator) and BAS0541 (Histidine kinase). BAS0540 BAS0541, the closest homolog of CiaRH of Streptococcus in B. anthracis, forms a functional TCS with BAS0541 displaying autophosphorylation and subsequent phosphotransfer to BAS0540. BAS0540 was also found to accept phosphate from physiologically relevant small molecule phosphodonors like acetyl phosphate and carbamoyl phosphate. Results of qRT-PCR and immunoblotting demonstrated that BAS0540 exhibits a constitutive expression throughout the growth of B. anthracis. Regulon prediction for BAS0540 in B. anthracis was done in silico using the consensus DNA binding sequence of CiaR of Streptococcus. The predicted regulon of BAS0540 comprised of 23 genes, which could be classified into 8 functionally diverse categories. None of the proven virulence factors were a part of the predicted regulon, an observation contrasting with the regulon of CiaRH in Streptococci. Electrophoretic mobility shift assay was used to show direct binding of purified BAS0540 to the upstream regions of 5 putative regulon candidates- BAS0540 gene itself; a gene predicted to encode cell division protein FtsA; a self-immunity gene; a RND family transporter gene and a gene encoding stress (heat) responsive protein. A significant enhancement in the DNA binding ability of BAS0540 was observed upon phosphorylation. Overexpression of response regulator BAS0540 in B. anthracis led to a prodigious increase of ~6 folds in the cell length, thereby conferring it a filamentous phenotype. Furthermore, the sporulation titer of the pathogen also decreased markedly by ~16 folds. Thus, this study characterizes a novel TCS of B. anthracis and elucidates its role in two of the most important physiological processes of the pathogen: cell division and sporulation. PMID- 27392064 TI - Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner. AB - Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV 2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV 1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release. PMID- 27392066 TI - Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer. PMID- 27392065 TI - Local Adaptation in European Firs Assessed through Extensive Sampling across Altitudinal Gradients in Southern Europe. AB - BACKGROUND: Local adaptation is a key driver of phenotypic and genetic divergence at loci responsible for adaptive traits variations in forest tree populations. Its experimental assessment requires rigorous sampling strategies such as those involving population pairs replicated across broad spatial scales. METHODS: A hierarchical Bayesian model of selection (HBM) that explicitly considers both the replication of the environmental contrast and the hierarchical genetic structure among replicated study sites is introduced. Its power was assessed through simulations and compared to classical 'within-site' approaches (FDIST, BAYESCAN) and a simplified, within-site, version of the model introduced here (SBM). RESULTS: HBM demonstrates that hierarchical approaches are very powerful to detect replicated patterns of adaptive divergence with low false-discovery (FDR) and false-non-discovery (FNR) rates compared to the analysis of different sites separately through within-site approaches. The hypothesis of local adaptation to altitude was further addressed by analyzing replicated Abies alba population pairs (low and high elevations) across the species' southern distribution range, where the effects of climatic selection are expected to be the strongest. For comparison, a single population pair from the closely related species A. cephalonica was also analyzed. The hierarchical model did not detect any pattern of adaptive divergence to altitude replicated in the different study sites. Instead, idiosyncratic patterns of local adaptation among sites were detected by within-site approaches. CONCLUSION: Hierarchical approaches may miss idiosyncratic patterns of adaptation among sites, and we strongly recommend the use of both hierarchical (multi-site) and classical (within-site) approaches when addressing the question of adaptation across broad spatial scales. PMID- 27392067 TI - Tryptophan catabolism in Pseudomonas aeruginosa and potential for inter-kingdom relationship. AB - BACKGROUND: Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host's immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury. RESULTS: Ex vivo, Pa secretes clinically relevant kynurenine levels (MUM to mM). Pa also secretes kynurenic acid and 3-OH kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production. CONCLUSION: Pa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host's tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection. PMID- 27392069 TI - Reversible and Precise Self-Assembly of Janus Metal-Organosilica Nanoparticles through a Linker-Free Approach. AB - Reversible self-assembly of nanoparticles into ordered structures is essential for both fundamental study and practical applications. Although extensive work has been conducted, the demand for simple, cheap, reversible, and versatile ordering methods is still a central issue in current nanoscience and nanotechnology. Here we report a reversible and precise self-assembly of nanoparticles through a linker-free and fast approach by manipulating the interparticle forces, e.g., van der Waals (VDW) force and electrostatic force. Because VDW force is nondirectional, an oriented interaction is achieved to induce the directional binding of nanoparticles utilizing the Janus nanostructure. An effective sol-gel approach has been developed to synthesize metal-organosilica Janus nanoparticles. Dimers and trimers can be obtained by tuning the steric hindrance. After assembly, "hot-spots" can be generated between adjacent nanoparticles, and dramatic enhancement has been observed in surface enhanced Raman scattering. The present strategy overcomes several limitations of existing approaches and allows the controlled assembly of small particles into various structures. PMID- 27392068 TI - Hyperecho PROPELLER-MRI: Application to rapid high-resolution motion-insensitive T2 -weighted black-blood imaging of the carotid arterial vessel wall and plaque. AB - PURPOSE: To demonstrate the usefulness of hyperecho and PROPELLER (HEP) for carotid arterial vessel wall imaging by using a quantitative comparison with conventional methods. PROPELLER is a motion-insensitive turbo spin-echo (TSE) sequence and has recently been utilized in magnetic resonance (MR) plaque imaging instead of double inversion recovery TSE (DIR-TSE). Wider blade-width, higher k space density, and an improved blood suppression effect result in better image quality. In this study we introduce a new combination of HEP. MATERIALS AND METHODS: A total of 17 subjects were examined on a 3.0T system. We conducted quantitative comparisons for signal-to-noise ratio (SNR), contrast-to-noise ratio, and image sharpness among HEP, DIR-TSE, and conventional PROPELLER (c PROPELLER). Subsequently, images obtained with DIR-TSE, c-PROPELLER, and HEP were visually evaluated using a three-point scale by two board-certified radiologists. RESULTS: HEP showed high SNR similar to c-PROPELLER, good T2 contrast approximating DIR-TSE, and better blood suppression compared with the other two methods (P < 0.05). The image sharpness of HEP (2.55 +/- 0.53) was higher than that of DIR-TSE (1.89 +/- 0.33) and the absence of ghost or streak artifacts in HEP (2.89 +/- 0.33) was better than that in both other methods (2.22 +/- 0.83 for DIR-TSE and 2.00 +/- 0.50 for c-PROPELLER) (P < 0.05). Furthermore, the degree of blood suppression, particularly in cases of slow or turbulent flow close to the atherosclerotic plaque, was identical for HEP (2.80 +/- 0.45) and DIR-TSE (2.80 +/- 0.45) but was significantly better than for c-PROPELLER (1.60 +/- 0.55) (P < 0.05). CONCLUSION: This study demonstrates the usefulness of HEP in the carotid arteries. HEP can provide higher-resolution T2 -weighted black-blood imaging without flow- and/or motion-related artifacts, compared to conventional techniques. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:515-524. PMID- 27392070 TI - Age of onset of bipolar disorder: Combined effect of childhood adversity and familial loading of psychiatric disorders. AB - BACKGROUND: Family history and adversity in childhood are two replicated risk factors for early onset bipolar disorder. However, their combined impact has not been adequately studied. METHODS: Based on questionnaire data from 968 outpatients with bipolar disorder who gave informed consent, the relationship and interaction of: 1) parental and grandparental total burden of psychiatric illness; and 2) the degree of adversity the patient experienced in childhood on their age of onset of bipolar disorder was examined with multiple regression and illustrated with a heat map. RESULTS: The familial loading and child adversity vulnerability factors were significantly related to age of onset of bipolar and their combined effect was even larger. A heat map showed that at the extremes (none of each factor vs high amounts of both) the average age of onset differed by almost 20 years (mean = 25.8 vs 5.9 years of age). LIMITATIONS: The data were not based on interviews of family members and came from unverified answers on a patient questionnaire. CONCLUSIONS: Family loading for psychiatric illness and adversity in childhood combine to have a very large influence on age of onset of bipolar disorder. These variables should be considered in assessment of risk for illness onset in different populations, the need for early intervention, and in the design of studies of primary and secondary prevention. PMID- 27392071 TI - Suicide attempters with Borderline Personality Disorder show differential orbitofrontal and parietal recruitment when reflecting on aversive memories. AB - Suicidal behavior and difficulty regulating emotions are hallmarks of Borderline Personality Disorder (BPD). This study examined neural links between emotion regulation and suicide risk in BPD. 60 individuals with BPD (all female, mean age = 28.9 years), 46 of whom had attempted suicide, completed a fMRI task involving recalling aversive personal memories. Distance trials assessed the ability to regulate emotion by recalling memories from a third-person, objective viewpoint. Immerse trials assessed emotional reactivity and involved recalling memories from a first-person perspective. Behaviorally, both groups reported less negative affect on Distance as compared to Immerse trials. Neurally, two sets of findings were obtained. The first reflected differences between attempters and non attempters. When immersing and distancing, attempters showed elevated recruitment of lateral orbitofrontal cortex, a brain region implicated in using negative cues to guide behavior. When distancing, attempters showed diminished recruitment of the precuneus, a region implicated in memory recall and perspective taking. The second set of findings related to individual differences in regulation success - the degree to which individuals used distancing to reduce negative affect. Here, we observed that attempters who successfully regulated exhibited precuneus recruitment that was more similar to non-attempters. These data provide insight into mechanisms underlying suicide attempts in BPD. Future work may examine if these findings generalize to other diagnoses and also whether prior findings in BPD differ across attempters and non-attempters. PMID- 27392072 TI - YCRD: Yeast Combinatorial Regulation Database. AB - In eukaryotes, the precise transcriptional control of gene expression is typically achieved through combinatorial regulation using cooperative transcription factors (TFs). Therefore, a database which provides regulatory associations between cooperative TFs and their target genes is helpful for biologists to study the molecular mechanisms of transcriptional regulation of gene expression. Because there is no such kind of databases in the public domain, this prompts us to construct a database, called Yeast Combinatorial Regulation Database (YCRD), which deposits 434,197 regulatory associations between 2535 cooperative TF pairs and 6243 genes. The comprehensive collection of more than 2500 cooperative TF pairs was retrieved from 17 existing algorithms in the literature. The target genes of a cooperative TF pair (e.g. TF1-TF2) are defined as the common target genes of TF1 and TF2, where a TF's experimentally validated target genes were downloaded from YEASTRACT database. In YCRD, users can (i) search the target genes of a cooperative TF pair of interest, (ii) search the cooperative TF pairs which regulate a gene of interest and (iii) identify important cooperative TF pairs which regulate a given set of genes. We believe that YCRD will be a valuable resource for yeast biologists to study combinatorial regulation of gene expression. YCRD is available at http://cosbi.ee.ncku.edu.tw/YCRD/ or http://cosbi2.ee.ncku.edu.tw/YCRD/. PMID- 27392073 TI - Typhoid fever: case report and literature review. AB - Typhoid fever remains a major health problem worldwide, in contrast to Chile, where this disease is an isolated finding. Clinical presentation is varied, mainly presenting with fever, malaise, abdominal discomfort, and nonspecific symptoms often confused with other causes of febrile syndrome. We report a six year-old, male patient presenting with fever of two weeks associated with gastrointestinal symptoms, malaise, hepatomegaly and elevated liver enzymes. Differential diagnoses were considered and a Widal reaction and two blood cultures were requested; both came back positive, confirming the diagnosis of typhoid fever caused by Salmonella typhi. Prior to diagnosis confirmation, empirical treatment was initiated with ceftriaxone and metronidazole, with partial response; then drug therapy was adjusted according to ciprofloxacin susceptibility testing with a favorable clinical response. We discuss diagnostic methods and treatment of enteric fever with special emphasis on typhoid fever. PMID- 27392074 TI - The Relationship between Common Genetic Markers of Breast Cancer Risk and Chemotherapy-Induced Toxicity: A Case-Control Study. AB - Ninety-four common genetic variants are confirmed to be associated with breast cancer. This study tested the hypothesis that breast cancer susceptibility variants may also be associated with chemotherapy-induced toxicity through shared mechanistic pathways such as DNA damage response, an association that, to our knowledge, has not been previously investigated. The study included breast cancer patients who received neoadjuvant/adjuvant chemotherapy from the Pharmacogenetic SNPs (PGSNPS) study. For each patient, a breast cancer polygenic risk score was created from the 94 breast cancer risk variants, all of which were genotyped or successfully imputed in PGSNPS. Logistic regression was performed to test the association with two clinically important toxicities: taxane- related neuropathy (n = 1279) and chemotherapy-induced neutropenia (n = 1676). This study was well powered (>=96%) to detect associations between polygenic risk score and chemotherapy toxicity. Patients with high breast cancer risk scores experienced less neutropenia compared to those with low risk scores (adjusted p-value = 0.06). Exploratory functional pathway analysis was performed and no functional pathways driving this trend were identified. Polygenic risk was not associated with taxane neuropathy (adjusted p-value = 0.48). These results suggest that breast cancer patients with high genetic risk of breast cancer, conferred by common variants, can safely receive standard chemotherapy without increased risk of taxane-related sensory neuropathy or chemotherapy-induced neutropenia and may experience less neutropenia. As neutropenia has previously been associated with improved survival and may reflect drug efficacy, these patients may be less likely to benefit from standard chemotherapy treatment. PMID- 27392075 TI - Human Y Chromosome Haplogroup N: A Non-trivial Time-Resolved Phylogeography that Cuts across Language Families. AB - The paternal haplogroup (hg) N is distributed from southeast Asia to eastern Europe. The demographic processes that have shaped the vast extent of this major Y chromosome lineage across numerous linguistically and autosomally divergent populations have previously been unresolved. On the basis of 94 high-coverage re sequenced Y chromosomes, we establish and date a detailed hg N phylogeny. We evaluate geographic structure by using 16 distinguishing binary markers in 1,631 hg N Y chromosomes from a collection of 6,521 samples from 56 populations. The more southerly distributed sub-clade N4 emerged before N2a1 and N3, found mostly in the north, but the latter two display more elaborate branching patterns, indicative of regional contrasts in recent expansions. In particular, a number of prominent and well-defined clades with common N3a3'6 ancestry occur in regionally dissimilar northern Eurasian populations, indicating almost simultaneous regional diversification and expansion within the last 5,000 years. This patrilineal genetic affinity is decoupled from the associated higher degree of language diversity. PMID- 27392077 TI - Autosomal-Recessive Mutations in the tRNA Splicing Endonuclease Subunit TSEN15 Cause Pontocerebellar Hypoplasia and Progressive Microcephaly. AB - The tRNA splicing endonuclease is a highly evolutionarily conserved protein complex, involved in the cleavage of intron-containing tRNAs. In human it consists of the catalytic subunits TSEN2 and TSEN34, as well as the non-catalytic TSEN54 and TSEN15. Recessive mutations in the corresponding genes of the first three are known to cause pontocerebellar hypoplasia (PCH) types 2A-C, 4, and 5. Here, we report three homozygous TSEN15 variants that cause a milder version of PCH2. The affected individuals showed progressive microcephaly, delayed developmental milestones, intellectual disability, and, in two out of four cases, epilepsy. None, however, displayed the central visual failure seen in PCH case subjects where other subunits of the TSEN are mutated, and only one was affected by the extensive motor defects that are typical in other forms of PCH2. The three amino acid substitutions impacted the protein level of TSEN15 and the stoichiometry of the interacting subunits in different ways, but all resulted in an almost complete loss of in vitro tRNA cleavage activity. Taken together, our results demonstrate that mutations in any known subunit of the TSEN complex can cause PCH and progressive microcephaly, emphasizing the importance of its function during brain development. PMID- 27392079 TI - Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. PMID- 27392076 TI - Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo Interstitial and Glomerulocystic Kidney Disease with Anemia. AB - Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1 c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)-both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD. PMID- 27392078 TI - Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa. AB - Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1) is a very rare autosomal-recessive disorder characterized by a complex phenotype with high neonatal lethality, associated with the following main clinical features: hyperthermia and feeding difficulties in the neonatal period, scoliosis, and paradoxical sweating induced by cold since early childhood. CS/CISS1 can be caused by mutations in cytokine receptor-like factor 1 (CRLF1). However, the physiopathological role of CRLF1 is still poorly understood. A subset of CS/CISS1 cases remain yet genetically unexplained after CRLF1 sequencing. In five of them, exome sequencing and targeted Sanger sequencing identified four homozygous disease-causing mutations in kelch-like family member 7 (KLHL7), affecting the Kelch domains of the protein. KLHL7 encodes a BTB-Kelch-related protein involved in the ubiquitination of target proteins for proteasome-mediated degradation. Mono-allelic substitutions in other domains of KLHL7 have been reported in three families affected by a late-onset form of autosomal-dominant retinitis pigmentosa. Retinitis pigmentosa was also present in two surviving children reported here carrying bi-allelic KLHL7 mutations. KLHL7 mutations are thus associated with a more severe phenotype in recessive than in dominant cases. Although these data further support the pathogenic role of KLHL7 mutations in a CS/CISS1-like phenotype, they do not explain all their clinical manifestations and highlight the high phenotypic heterogeneity associated with mutations in KLHL7. PMID- 27392081 TI - Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. PMID- 27392082 TI - Characterization of the binding of neomycin/paromomycin sulfate with DNA using acridine orange as fluorescence probe and molecular docking technique. AB - The binding of neomycin sulfate (NS)/paromomycin sulfate (PS) with DNA was investigated by fluorescence quenching using acridine orange (AO) as a fluorescence probe. Fluorescence lifetime, FT-IR, circular dichroism (CD), relative viscosity, ionic strength, DNA melting temperature, and molecular docking were performed to explore the binding mechanism. The binding constant of NS/PS and DNA was 6.70 * 103/1.44 * 103 L mol-1 at 291 K. The values of DeltaHtheta, DeltaStheta, and DeltaGtheta suggested that van der Waals force or hydrogen bond might be the main binding force between NS/PS and DNA. The results of Stern-Volmer plots and fluorescence lifetime measurements all revealed that NS/PS quenching the fluorescence of DNA-AO was static in nature. FT-IR indicated that the interaction between DNA and NS/PS did occur. The relative viscosity and melting temperature of DNA were almost unchanged when NS/PS was introduced to the solution. The fluorescence intensity of NS/PS-DNA-AO was decreased with the increase in the ionic strength. For CD spectra of DNA, the intensity of positive band at nearly 275 nm was decreased and that of negative band at nearly 245 nm was increased with the increase in the concentration of NS/PS. The binding constant of NS/PS with double-stranded DNA (dsDNA) was larger than that of NS/PS with single-stranded DNA (ssDNA). From these studies, the binding mode of NS/PS with DNA was evaluated to be groove binding. The results of molecular docking further indicated that NS/PS could enter into the minor groove in the A-T rich region of DNA. PMID- 27392083 TI - Using Stable Isotopes of Carbon and Nitrogen to Mark Wild Populations of Anopheles and Aedes Mosquitoes in South-Eastern Tanzania. AB - BACKGROUND: Marking wild mosquitoes is important for understanding their ecology, behaviours and role in disease transmission. Traditional insect marking techniques include using fluorescent dyes, protein labels, radioactive labels and tags, but such techniques have various limitations; notably low marker retention and inability to mark wild mosquitoes at source. Stable isotopes are gaining wide spread use for non-invasive marking of arthropods, permitting greater understanding of mosquito dispersal and responses to interventions. We describe here a simple technique for marking naturally-breeding malaria and dengue vectors using stable isotopes of nitrogen (15N) and carbon (13C), and describe potential field applications. METHODS: We created man-made aquatic mosquito habitats and added either 15N-labelled potassium nitrate or 13C-labelled glucose, leaving non adulterated habitats as controls. We then allowed wild mosquitoes to lay eggs in these habitats and monitored their development in situ. Pupae were collected promptly as they appeared and kept in netting cages. Emergent adults (in pools of ~4 mosquitoes/pool) and individually stored pupae were desiccated and analysed using Isotope Ratio Mass Spectrometry (IRMS). FINDINGS: Anopheles gambiae s.l and Aedes spp. from enriched 13C and enriched 15N larval habitats had significantly higher isotopic levels than controls (P = 0.005), and both isotopes produced sufficient distinction between marked and unmarked mosquitoes. Mean delta15N for enriched females and males were 275.6+/-65.1 and 248.0+/-54.6, while mean delta15N in controls were 2.1+/-0.1 and 3.9+/-1.7 respectively. Similarly, mean delta13C for enriched females and males were 36.08+/-5.28 and 38.5+/-6.86, compared to -4.3+/-0.2 and -7.9+/-3.6 in controls respectively. Mean delta15N and delta13C was significantly higher in any pool containing at least one enriched mosquito compared to pools with all unenriched mosquitoes, P<0.001. In all cases, there were variations in standardized isotopic ratios between mosquito species. CONCLUSION: Enrichment of semi-natural mosquito larval habitats with stable isotopes of nitrogen and carbon resulted in effective marking of Anopheles and Aedes mosquitoes colonizing these habitats. This approach can significantly enhance studies on mosquito eco-physiology, dispersal, pathogen transmission and responses to control measures. PMID- 27392080 TI - Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. PMID- 27392084 TI - Engagement of distinct epitopes on CD43 induces different co-stimulatory pathways in human T cells. AB - Co-receptors, being either co-stimulatory or co-inhibitory, play a pivotal role in T-cell immunity. Several studies have indicated that CD43, one of the abundant T-cell surface glycoproteins, acts not only as a potent co-receptor but also as a negative regulator for T-cell activation. Here we demonstrate that co-stimulation of human peripheral blood (PB) T cells through two distinct CD43 epitopes recognized by monoclonal antibodies (mAb) CD43-6E5 (T6E5-act ) and CD43-10G7 (T10G7-act ) potently induced T-cell proliferation. However, T-cell co stimulation through two CD43 epitopes differentially regulated activation of nuclear factor of activated T cells (NFAT) and nuclear factor-kappaB (NF-kappaB) transcription factors, T-cell cytokine production and effector function. T6E5-act produced high levels of interleukin-22 (IL-22) and interferon-gamma (IFN-gamma) similar to T cells activated via CD28 (TCD28-act ), whereas T10G7-act produced low levels of inflammatory cytokines but higher levels of regulatory cytokines transforming growth factor-beta (TGF-beta) and interleukin-35 (IL-35). Compared with T6E5-act or to TCD28-act , T10G7-act performed poorly in response to re stimulation and further acquired a T-cell suppressive function. T10G7-act did not directly inhibit proliferation of responder T cells, but formed stable heterotypic clusters with dendritic cells (DC) via CD2 to constrain activation of responder T cells. Together, our data demonstrate that CD43 is a unique and polarizing regulator of T-cell function. PMID- 27392085 TI - Speciation and ecological success in dimly lit waters: horizontal gene transfer in a green sulfur bacteria bloom unveiled by metagenomic assembly. AB - A natural planktonic bloom of a brown-pigmented photosynthetic green sulfur bacteria (GSB) from the disphotic zone of karstic Lake Banyoles (NE Spain) was studied as a natural enrichment culture from which a nearly complete genome was obtained after metagenomic assembly. We showed in situ a case where horizontal gene transfer (HGT) explained the ecological success of a natural population unveiling ecosystem-specific adaptations. The uncultured brown-pigmented GSB was 99.7% identical in the 16S rRNA gene sequence to its green-pigmented cultured counterpart Chlorobium luteolum DSM 273T. Several differences were detected for ferrous iron acquisition potential, ATP synthesis and gas vesicle formation, although the most striking trait was related to pigment biosynthesis strategy. Chl. luteolum DSM 273T synthesizes bacteriochlorophyll (BChl) c, whereas Chl. luteolum CIII incorporated by HGT a 18-kbp cluster with the genes needed for BChl e and specific carotenoids biosynthesis that provided ecophysiological advantages to successfully colonize the dimly lit waters. We also genomically characterized what we believe to be the first described GSB phage, which based on the metagenomic coverage was likely in an active state of lytic infection. Overall, we observed spread HGT and we unveiled clear evidence for virus-mediated HGT in a natural population of photosynthetic GSB. PMID- 27392086 TI - Differential specificity between closely related corals and abundant Endozoicomonas endosymbionts across global scales. AB - Reef-building corals are well regarded not only for their obligate association with endosymbiotic algae, but also with prokaryotic symbionts, the specificity of which remains elusive. To identify the central microbial symbionts of corals, their specificity across species and conservation over geographic regions, we sequenced partial SSU ribosomal RNA genes of Bacteria and Archaea from the common corals Stylophora pistillata and Pocillopora verrucosa across 28 reefs within seven major geographical regions. We demonstrate that both corals harbor Endozoicomonas bacteria as their prevalent symbiont. Importantly, catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) with Endozoicomonas-specific probes confirmed their residence as large aggregations deep within coral tissues. Using fine-scale genotyping techniques and single-cell genomics, we demonstrate that P. verrucosa harbors the same Endozoicomonas, whereas S. pistillata associates with geographically distinct genotypes. This specificity may be shaped by the different reproductive strategies of the hosts, potentially uncovering a pattern of symbiont selection that is linked to life history. Spawning corals such as P. verrucosa acquire prokaryotes from the environment. In contrast, brooding corals such as S. pistillata release symbiont packed planula larvae, which may explain a strong regional signature in their microbiome. Our work contributes to the factors underlying microbiome specificity and adds detail to coral holobiont functioning. PMID- 27392088 TI - Brain Development, Impulsivity, Risky Decision Making, and Cognitive Control: Integrating Cognitive and Socioemotional Processes During Adolescence-An Introduction to the Special Issue. PMID- 27392087 TI - An unusual strategy for the anoxic biodegradation of phthalate. AB - In the past two decades, the study of oxygen-independent degradation of widely abundant aromatic compounds in anaerobic bacteria has revealed numerous unprecedented enzymatic principles. Surprisingly, the organisms, metabolites and enzymes involved in the degradation of o-phthalate (1,2-dicarboxybenzene), mainly derived from phthalate esters that are annually produced at the million ton scale, are sparsely known. Here, we demonstrate a previously unknown capacity of complete phthalate degradation in established aromatic compound-degrading, denitrifying model organisms of the genera Thauera, Azoarcus and 'Aromatoleum'. Differential proteome analyses revealed phthalate-induced gene clusters involved in uptake and conversion of phthalate to the central intermediate benzoyl-CoA. Enzyme assays provided in vitro evidence for the formation of phthaloyl-CoA by a succinyl-CoA- and phthalate-specific CoA transferase, which is essential for the subsequent oxygen-sensitive decarboxylation to benzoyl-CoA. The extreme instability of the phthaloyl-CoA intermediate requires highly balanced CoA transferase and decarboxylase activities to avoid its cellular accumulation. Phylogenetic analysis revealed phthaloyl-CoA decarboxylase as a novel member of the UbiD-like, (de)carboxylase enzyme family. Homologs of the encoding gene form a phylogenetic cluster and are found in soil, freshwater and marine bacteria; an ongoing global distribution of a possibly only recently evolved degradation pathway is suggested. PMID- 27392089 TI - Neural Correlates of Response Inhibition in Adolescents Prospectively Predict Regular Tobacco Smoking. AB - Inhibitory deficits have been widely reported in addiction; however, it remains unclear whether such deficits represent a determinant or a consequence of substance use. Here we show, using a prospective longitudinal design, that developmental abnormalities in the neural correlates of response inhibition in adolescents increase the risk for subsequent cigarette smoking. Reduced No-Go P3 amplitude, delayed latency of Go P3 peak, and reduced synchrony of neuronal oscillations at age 14 prospectively predicted regular smoking at age 18. The present findings suggest that functional brain correlates of response inhibition represent a developmental marker of risk for future substance abuse. PMID- 27392091 TI - A new device for measuring isometric force of the craniocervical flexor and extensor muscles and its reliability. AB - OBJECTIVE: Craniocervical (CC) muscles control posture of the CC area. Muscle imbalance at this area induces musculoskeletal disorders. The purpose of this study was to develop a device for measuring isometric force of CC flexor and extensor muscles and to evaluate its intra-rater reliability. METHOD: Isometric force of CC flexor and extensor muscles was measured in 20 women by one examiner on two days with a custom-made device. The intra-class correlation coefficient (ICC), standard error of measurements (SEM), smallest detectable difference (SDD), and Pearson correlation coefficient were computed. RESULTS: The results of this study revealed that this device had excellent reliability (ICC: 0.98, SEM: 2.29 N, SDD: 6.36 N, Pearson correlation coefficient: 0.97 for CC flexor muscles and ICC: 0.97, SEM: 2.13 N, SDD: 5.91 N, Pearson correlation coefficient: 0.94 for CC extensor muscles). DISCUSSION: This new device can improve knowledge about the CC muscle and efficacy of treatments in patients with poor posture. PMID- 27392090 TI - Potential Application of the Oryza sativa Monodehydroascorbate Reductase Gene (OsMDHAR) to Improve the Stress Tolerance and Fermentative Capacity of Saccharomyces cerevisiae. AB - Monodehydroascorbate reductase (MDHAR; EC 1.6.5.4) is an important enzyme for ascorbate recycling. To examine whether heterologous expression of MDHAR from Oryza sativa (OsMDHAR) can prevent the deleterious effects of unfavorable growth conditions, we constructed a transgenic yeast strain harboring a recombinant plasmid carrying OsMDHAR (p426GPD::OsMDHAR). OsMDHAR-expressing yeast cells displayed enhanced tolerance to hydrogen peroxide by maintaining redox homoeostasis, proteostasis, and the ascorbate (AsA)-like pool following the accumulation of antioxidant enzymes and molecules, metabolic enzymes, and molecular chaperones and their cofactors, compared to wild-type (WT) cells carrying vector alone. The addition of exogenous AsA or its analogue isoascorbic acid increased the viability of WT and ara2Delta cells under oxidative stress. Furthermore, the survival of OsMDHAR-expressing cells was greater than that of WT cells when cells at mid-log growth phase were exposed to high concentrations of ethanol. High OsMDHAR expression also improved the fermentative capacity of the yeast during glucose-based batch fermentation at a standard cultivation temperature (30 degrees C). The alcohol yield of OsMDHAR-expressing transgenic yeast during fermentation was approximately 25% (0.18 g.g-1) higher than that of WT yeast. Accordingly, OsMDHAR-expressing transgenic yeast showed prolonged survival during the environmental stresses produced during fermentation. These results suggest that heterologous OsMDHAR expression increases tolerance to reactive oxygen species-induced oxidative stress by improving cellular redox homeostasis and improves survival during fermentation, which enhances fermentative capacity. PMID- 27392092 TI - Ikarugamycin: A Natural Product Inhibitor of Clathrin-Mediated Endocytosis. AB - Ikarugamycin (IKA) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low-density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin-mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We show that IKA has an IC50 of 2.7 MUm in H1299 cells and acutely inhibits CME, but not other endocytic pathways, in a panel of cell lines. Although long-term incubation with IKA has cytotoxic effects, the short-term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking. PMID- 27392093 TI - Postoperative Respiratory Function and Survival After Pneumonectomy in Dogs and Cats. AB - OBJECTIVE: To describe indications for, and outcomes after, pneumonectomy in dogs and cats, including assessment of immediate postoperative respiratory function in comparison to dogs undergoing single lung lobectomy. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n=16) and cats (n=7) with naturally occurring pulmonary disease. METHODS: Medical records (1990-2014) of dogs and cats undergoing right or left pneumonectomy were reviewed. Data retrieved included signalment, history, preoperative diagnostics, operative descriptions, postoperative data including respiratory function, and postdischarge outcomes. For respiratory function comparisons, medical records of dogs having undergone a single lung lobectomy via median sternotomy (n=15) or intercostal thoracotomy (n=15) were reviewed. RESULTS: Twenty-three cases (16 dogs, 7 cats) were included. Pneumonectomy was performed for congenital (1 dog, 1 cat), neoplastic (8 dogs, 1 cat), and infectious (7 dogs, 5 cats) disease. Postoperative aspiration pneumonia occurred in 2 dogs; 15 of 16 dogs (94%) and 6/7 cats (86%) survived to hospital discharge. After pneumonectomy, dogs had a significantly higher postoperative PaO2 on 21% oxygen (P=.033) and lower postoperative A-a gradient (P=.004) compared to dogs undergoing single lung lobectomy. Survival times (right-censored at last follow-up) for dogs ranged from 2 days to 7 years (estimated median=1,868 days) and for cats from 1-585 days. CONCLUSION: Dogs and cats have acceptable respiratory function immediately postoperatively and most have protracted long-term survival after pneumonectomy for a variety of pulmonary diseases. PMID- 27392094 TI - Reverse Signaling by Semaphorin-6A Regulates Cellular Aggregation and Neuronal Morphology. AB - The transmembrane semaphorin, Sema6A, has important roles in axon guidance, cell migration and neuronal connectivity in multiple regions of the nervous system, mediated by context-dependent interactions with plexin receptors, PlxnA2 and PlxnA4. Here, we demonstrate that Sema6A can also signal cell-autonomously, in two modes, constitutively, or in response to higher-order clustering mediated by either PlxnA2-binding or chemically induced multimerisation. Sema6A activation stimulates recruitment of Abl to the cytoplasmic domain of Sema6A and phos!phorylation of this cytoplasmic tyrosine kinase, as well as phosphorylation of additional cytoskeletal regulators. Sema6A reverse signaling affects the surface area and cellular complexity of non-neuronal cells and aggregation and neurite formation of primary neurons in vitro. Sema6A also interacts with PlxnA2 in cis, which reduces binding by PlxnA2 of Sema6A in trans but not vice versa. These experiments reveal the complex nature of Sema6A biochemical functions and the molecular logic of the context-dependent interactions between Sema6A and PlxnA2. PMID- 27392095 TI - HnRNP Q Has a Suppressive Role in the Translation of Mouse Cryptochrome1. AB - Precise regulation of gene expression is especially important for circadian timekeeping which is maintained by the proper oscillation of the mRNA and protein of clock genes and clock-controlled genes. As a main component of the core negative arm feedback loops in the circadian clock, the Cry1 gene contributes to the maintenance of behavioral and molecular rhythmicity. Despite the central role of Cry1, the molecular mechanisms regulating expression levels of Cry1 mRNA and protein are not well defined. In particular, the post-transcriptional regulation of Cry1 mRNA fate decisions is unclear. Here, we demonstrate that hnRNP Q binds to mCry1 mRNA via the 5'UTR. Furthermore, hnRNP Q inhibits the translation of mCry1 mRNA, leading to altered rhythmicity in the mCRY1 protein profile. PMID- 27392096 TI - Drying and recovery of aerobic granules. AB - To dehydrate aerobic granules to bone-dry form was proposed as a promising option for long-term storage of aerobic granules. This study cultivated aerobic granules with high proteins/polysaccharide ratio and then dried these granules using seven protocols: drying at 37 degrees C, 60 degrees C, 4 degrees C, under sunlight, in dark, in a flowing air stream or in concentrated acetone solutions. All dried granules experienced volume shrinkage of over 80% without major structural breakdown. After three recovery batches, although with loss of part of the volatile suspended solids, all dried granules were restored most of their original size and organic matter degradation capabilities. The strains that can survive over the drying and storage periods were also identified. Once the granules were dried, they can be stored over long period of time, with minimal impact yielded by the applied drying protocols. PMID- 27392097 TI - "VACUOLE" SIGN ADJACENT TO RETINAL PIGMENT EPITHELIAL DEFECTS ON SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN CENTRAL SEROUS CHORIORETINOPATHY ASSOCIATED WITH SUBRETINAL FIBRIN. AB - PURPOSE: To report spectral domain optical coherence tomography features in central serous chorioretinopathy associated with subretinal fibrin. METHOD: Retrospective observational case series of patients with central serous chorioretinopathy with subretinal fibrin imaged with spectral domain optical coherence tomography. RESULT: Twenty-three eyes of 23 patients (19 males and 4 females), with mean age of 39.09 +/- 5.8 years were included in the study. Subretinal fibrin clinically ranged from localized well-defined areas to extensive ill-defined areas. Along with the presence of subretinal hyperreflectivity (n = 23, 100%), corresponding to fibrin, spectral domain optical coherence tomography also revealed the presence of the retinal pigment epithelial (RPE) defects (n = 23, 100%) in all eyes with an adjacent well-defined hyporeflective vacuole. In 19 eyes wherein fundus fluorescein was performed, the RPE defects and vacuoles corresponded to the site of RPE leak. Serous pigment epithelial detachments (n = 18, 78.2%), multiple RPE defects in the same eye (n = 5), and multiple RPE defects in same pigment epithelial detachment (n = 1) were few other interesting features observed. CONCLUSION: The presence of a hyporeflective vacuole amid the hyperreflective fibrin adjacent to RPE defects probably indicates the site of constant fluid egress and is an important sign of disease activity especially in cases where fundus fluorescein angiography is not possible. PMID- 27392099 TI - Two-dimensional lateral heterojunction through bandgap engineering of MoS2 via oxygen plasma. AB - The present study explores the structural, optical (photoluminescence (PL)), and electrical properties of lateral heterojunctions fabricated by selective exposure of mechanically exfoliated few layer two-dimensional (2D) molybdenum disulfide (MoS2) flakes under oxygen (O2)-plasma. Raman spectra of the plasma exposed MoS2 flakes show a significant loss in the structural quality due to lattice distortion and creation of oxygen-containing domains in comparison to the pristine part of the same flake. The PL mapping evidences the complete quenching of peak A and B consistent with a change in the exciton states of MoS2 after the plasma treatment, indicating a significant change in its band gap properties. The electrical transport measurements performed across the pristine and the plasma exposed MoS2 flake exhibit a gate tunable current rectification behavior with a rectification ratio up to 1.3 * 10(3) due to the band-offset at the pristine and plasma-exposed MoS2 interface. Our Raman, PL, and electrical transport data confirm the formation of an excellent lateral heterojunction in 2D MoS2 through its bandgap modulation via oxygen plasma. PMID- 27392098 TI - Spatial and Molecular Epidemiology of Giardia intestinalis Deep in the Amazon, Brazil. AB - BACKGROUND: Current control policies for intestinal parasitosis focuses on soil transmitted helminths, being ineffective against Giardia intestinalis, a highly prevalent protozoon that impacts children's nutritional status in developing countries. The objective of this study was to explore spatial and molecular epidemiology of Giardia intestinalis in children of Amerindian descent in the Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional survey was performed in the Brazilian Amazon with 433 children aged 1 to 14 years. Fecal samples were processed through parasitological techniques and molecular characterization. Prevalence of G. intestinalis infection was 16.9% (73/433), reaching 22.2% (35/158) among children aged 2-5 years, and a wide distribution throughout the city with some hot spots. Positivity-rate was similar among children living in distinct socioeconomic strata (48/280 [17.1%] and 19/116 [16.4%] below and above the poverty line, respectively). Sequencing of the beta giardin gene revealed 52.2% (n = 12) of assemblage A and 47.8% (n = 11) of assemblage B with high haplotype diversity for the latter. The isolates clustered into two well-supported G. intestinalis clades. A total of 38 haplotypes were obtained, with the following subassemblages distribution: 5.3% (n = 2) AII, 26.3% (n = 10) AIII, 7.9% (n = 3) BIII, and 60.5% (n = 23) new B genotypes not previously described. CONCLUSIONS/SIGNIFICANCE: Giardia intestinalis infection presents a high prevalence rate among Amerindian descended children living in Santa Isabel do Rio Negro/Amazon. The wide distribution observed in a small city suggests the presence of multiple sources of infection, which could be related to environmental contamination with feces, possibly of human and animal origin, highlighting the need of improving sanitation, safe water supply and access to diagnosis and adequate treatment of infections. PMID- 27392100 TI - Coming in Postgraduate Medicine. PMID- 27392101 TI - Problems/Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27392102 TI - What's Happening in Medicine! PMID- 27392103 TI - Washington Report on Health. PMID- 27392104 TI - Meetings and Courses. PMID- 27392107 TI - The Medical Muse. PMID- 27392109 TI - Coupling and optimisation of online nuclear magnetic resonance spectroscopy and mass spectrometry for process monitoring to cover the broad range of process concentration. AB - Real time online monitoring of chemical processes can be carried out by a number of analytical techniques, including optical and vibrational spectroscopies, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). As each technique has unique advantages and challenges, combinations are an attractive option. The combination of a 500-MHz 1 H NMR and a small footprint mass spectrometer to monitor a batch reaction at process concentration was investigated. The mass spectrometer was coupled into the flow path of an online reaction monitoring NMR. Reaction mixture was pumped from a 100-ml vessel to an NMR flow tube before returning to the vessel. Small aliquots were diverted into a sampling make-up flow using an active flow splitter and passed to the mass spectrometer. Advantages of the combination were observed. 1 H NMR was ideal for quantitation of high level components, whereas MS showed a greater capability for detecting those at low level. In preliminary experiments MS produced a limited linear relationship with concentration (0.02% to 2% relative concentration, 0.01 mg/ml-1.25 mg/ml), because of signal saturation at the higher concentrations. NMR was unable to detect components below 0.1% relative to concentration maximum. Optimisation of sample transfer to the MS extended the linearity to 10% relative to the concentration maximum. Therefore, the combination of online NMR and MS allows both qualitative and quantitative analysis of reaction components over the full process range. The application of the combination was demonstrated by monitoring a batch chemical reaction and this is described. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27392111 TI - The safety of chronic antithrombotic therapy in patients with factor XI deficiency. PMID- 27392112 TI - One-Step Production of 1,3-Butadiene from 2,3-Butanediol Dehydration. AB - We report the direct production of 1,3-butadiene from the dehydration of 2,3 butandiol by using alumina as catalyst. Under optimized kinetic reaction conditions, the production of methyl ethyl ketone and isobutyraldehyde, formed via the pinacol-pinacolone rearrangement, was markedly reduced and almost 80 % selectivity to 1,3-butadiene and 1,3-butadiene could be achieved. The presence of water plays a critical role in the inhibition of oligomerization. The amphoteric nature of gamma-Al2 O3 was identified as important and this contributed to the improved catalytic selectivity when compared with other acidic catalysts. PMID- 27392113 TI - Correction to: Effects of Different Combinations of Er:YAG Laser-Adhesives on Enamel Demineralization and Bracket Bond Strength. Photomed Laser Surg 2016;34:164-170; DOI: 10.1089/pho.2015.4041. AB - OBJECTIVE: The purpose of this study was to investigate the demineralization around brackets and shear bond strength (SBS) of brackets bonded to Er:YAG laser irradiated enamel at different power settings with various adhesive systems combinations. METHODS: A total of 108 premolar teeth were used for SBS testing and an additional 54 teeth were used to evaluate demineralization. Teeth were assigned into three groups according to the etching procedure, then each group divided into three subgroups based on the application of different adhesive systems. There were a total of nine groups as follows: Group 1: Acid + Transbond XT Primer; group 2: Er:YAG (100 mJ, 10 Hz) etching + Transbond XT Primer; group 3: Er:YAG (200 mJ, 10 Hz) etching + Transbond XT Primer; group 4: Transbond Plus self-etching primer (SEP); group 5: Er:YAG (100 mJ, 10 Hz) etching + Transbond Plus SEP; group 6: Er:YAG (200 mJ, 10 Hz) etching + Transbond Plus SEP; group 7: Clearfil Protect Bond; group 8: Er:YAG (100 mJ, 10 Hz) etching + Clearfil Protect Bond; group 9: Er:YAG (200 mJ, 10 Hz) etching + Clearfil Protect Bond. Brackets were bonded with Transbond XT Adhesive Paste in all groups. Teeth to be evaluated for demineralization and SBS were exposed to pH and thermal cyclings, respectively. Then, demineralization samples were scanned with micro-CT to determine lesion depth values. For SBS test, a universal testing machine was used and adhesive remnant index was scored after debonding. Data were analyzed statistically. RESULTS: No significant differences were found among the lesion depth values of the various groups, except for G7 and G8, in which the lowest values were recorded. The lowest SBS values were in G7, whereas the highest were in G9. The differences between the other groups were not significant. CONCLUSIONS: Er:YAG laser did not have a positive effect on prevention of enamel demineralization. When two step self-etch adhesive is preferred for bonding brackets, laser etching at 1 W (100 mJ, 10 Hz) is suggested to improve SBS of brackets. The authors regret this error. PMID- 27392114 TI - Flagellin-rPAc vaccine inhibits biofilm formation but not proliferation of S. mutans. AB - As the main etiologic bacterium of dental caries, Streptococcus mutans (S. mutans) has been considered as the primary object of vaccine research. We previously constructed a recombinant flagellin-rPAc fusion protein (KF-rPAc) that consists of an alanine-rich region to proline-rich region fragment of PAc (rPAc) from S. mutans and flagellin KF from E.coli K12 strain. Intranasal (i.n) immunization of KF-rPAc could induce high level of rPAc-specific antibody responses and offer robust protection against dental caries. In caries development, biofilm formation was considered as the necessary process involved. As PAc possesses other activities besides affecting adherence of S. mutans to salivary glycoproteins, we wondered whether rPAc-specific antibody responses induced by KF-rPAc could inhibit biofilm formation. Hence, in the present study, a simple and convenient in vitro biofilm model of S. mutans was constructed without saliva pre-coated. Both serum and saliva from KF-rPAc immunized rats significantly inhibited biofilm formation. Moreover, with the presence of serum or saliva, the biofilm formation is negatively correlated with the level of rPAc specific antibody, and positively correlated with caries scores in rat. Moreover, in immunized mice, the level of rPAc-specific antibody also negatively correlated with the biofilm formation. Unlike ampicillin, serum of KF-rPAc immunized mice only inhibited biofilm formation but not proliferation. All together, we discovered that besides the well known blocking adherence of S. mutans to salivary glycoproteins by rPAc-specific antibody, flagellin-rPAc vaccine could also protects tooth from caries by inhibiting biofilm structure formation in between bacteria. PMID- 27392115 TI - Acoustic radiation force imaging of the thyroid-generation of reference values by Virtual Touch Imaging and Quantification. AB - OBJECTIVES: To investigate potential subject-related confounding factors for thyroid acoustic radiation force impulse (ARFI) elastography. METHODS AND MATERIALS: A total of 194 subjects participated in the study. RESULTS: The standard values in the right lobe were 2.52+/-0.35m/s (ventral half) and 2.43+/ 0.40m/s (dorsal half). In the left lobe, velocities of 2.56+/-0.37m/s (ventral) and 2.48+/-0.42m/s (dorsal) were noted. A clear difference was observed between measurement values in the ventral and dorsal half (P<.0001). By contrast, none of the other factors exerted any effect on the measurements. CONCLUSIONS: ARFI Virtual Touch Imaging and Quantification appears to be a suitable and relatively robust method for examining the thyroid gland. PMID- 27392116 TI - Effect of Selenium Supplementation on Recurrent Hyperthyroidism Caused by Graves' Disease: A Prospective Pilot Study. AB - The effect of selenium supplementation on recurrent hyperthyroidism caused by Graves' disease is unclear. Our study aimed to assess the efficacy of selenium supplementation therapy on recurrent Graves' disease. Forty-one patients with recurrent Graves' disease were enrolled in this study. All patients received the routine treatment using methimazole (MMI), while patients allocated to the selenium group received additional selenium therapy for 6 months. The influence of selenium supplementation on the concentrations of thyroid stimulating hormone (TSH), anti-TSH-receptor antibodies (TRAb), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed. The remission rate was also compared between 2 groups. There was no obvious difference in the demographic data and the levels of serum FT4, FT3, TSH, and TRAb between the 2 groups at baseline. Both FT4 and FT3 decreased more at 2 months in the selenium group than the controls, while the TSH level increased more in patients receiving selenium supplementation (p<0.05). The TRAb level was significantly lower in patients receiving selenium supplementation (2.4 IU/l vs. 5.6 IU/l, p=0.04). The percentages of patients with normal TRAb level at 6 months was also significantly higher in the selenium group (19.0 vs. 0%, p=0.016). Kaplan-Meier survival curve showed patients receiving selenium supplementation had a significantly higher rate of remission than controls (Log-rank test p=0.008). In conclusion, selenium supplementation can enhance the effect of antithyroid drugs in patients with recurrent Graves' disease. Randomized trials with large number of participants are needed to validate the finding above. PMID- 27392117 TI - Metabolism Regulation by Estrogens and Their Receptors in the Central Nervous System Before and After Menopause. AB - Estrogens through their intracellular receptors regulate various aspects of glucose and lipid metabolism. The effects of estrogens in metabolism can be mediated by their receptors located in different areas of the brain such as the hypothalamus, which is involved in the control of food intake, energy expenditure, and body weight homeostasis. Alterations in the metabolic regulation by estrogens participate in the pathogenesis of the metabolic syndrome and cardiovascular diseases in women. The metabolic syndrome is an important disease around the world, consisting in a combination of characteristics including abdominal obesity, dyslipidemia, hypertension, and insulin resistance. It increases the risk of cardiovascular disease and type 2 diabetes. It has been suggested that there is an increase in the incidence of metabolic syndrome during menopause due to estrogens deficiency. Estrogens replacement improves insulin sensitivity and reduces the risk of diabetes in rats. In the brain, estrogens through the interaction with their receptors regulate the activity of neurons involved in energy homeostasis, including appetite and satiety. Thus, estradiol and their receptors in the hypothalamus play a key role in metabolic syndrome development during menopause. PMID- 27392119 TI - Glucocorticoid-induced hyperglycaemia in respiratory disease: a systematic review and meta-analysis. AB - The relative risk of glucocorticoid-induced hyperglycaemia is poorly quantified. We undertook a meta-analysis to estimate the association between glucocorticoid treatment and hyperglycaemia, overall and separately in individuals with and without diabetes and underlying respiratory disease. We searched electronic databases for clinical trials of adults randomized to either glucocorticoid treatment or placebo. Eight articles comprising 2121 participants were identified. We performed a random effects meta-analysis to determine relative risks for the associations between glucocorticoid use and both hyperglycaemia and starting hypoglycaemic therapy. In all individuals, the relative risk of hyperglycaemia comparing glucocorticoid treatment with placebo was 1.72 [95% confidence interval (CI) 1.50-2.04; p < .001]. The relative risks in individuals with and those without diabetes were 2.10 (95% CI 0.92-5.02; p = .079) and 1.50 (95% CI 0.79-2.86; p = .22), respectively. In all individuals, the relative risk of hyperglycaemia requiring initiation of hypoglycaemic therapy, comparing glucocorticoid treatment with placebo, was 1.73 (95% CI 1.40-2.14; p < .001). In conclusion, glucocorticoid therapy increases the risk of hyperglycaemia in all individuals with underlying respiratory disease but not when diabetic status is analysed separately. PMID- 27392118 TI - Irrigation dose and plant density affect the volatile composition and sensory quality of dill (Anethum graveolens L.). AB - BACKGROUND: Two independent field experiments were carried out to investigate the influence of (i) three irrigation treatments (ID0 = 1585 m3 ha-1 , considered as a control; ID1 = 1015 m3 ha-1 ; and ID2 = 2180 m3 ha-1 ) and (ii) three plant density treatments (PD0 = 5.56 plants m-2 , considered as a control; PD1 = 4.44 plants m-2 ; and PD2 = 7.41 plants m-2 ) on the production, volatile composition of essential oil, and sensory quality of dill. RESULTS: The highest plant yield was obtained with intermediate conditions of both irrigation dose (ID0) and plant density (PD0). The main compounds of the essential oil were alpha-phellandrene, dill ether and beta-phellandrene. The highest irrigation dose (ID2) produced the highest concentrations of most of the main compounds: alpha-phellandrene (49.5 mg per 100 g), beta-phellandrene (6.89 mg per 100 g) and limonene (2.49 mg per 100 g). A similar pattern was found for the highest plant density (PD2): alpha phellandrene (71.0 mg per 100 g), dill ether (16.7 mg per 100 g) and beta phellandrene (9.70 mg per 100 g). The use of descriptive sensory analysis helped in reaching a final decision, and the dill plants with the highest sensory quality were those of the ID2 and PD0 treatments. CONCLUSION: The final recommendation is to use the irrigation dose ID2 and the plant density PD2 if the objective is to produce dill samples with the highest aromatic and sensory quality; however, if the only objective is to produce high amounts of dill, the best options are ID0 and PD0. (c) 2016 Society of Chemical Industry. PMID- 27392120 TI - Patterns of productive activity engagement as a longitudinal predictor of depressive symptoms among older adults in urban China. AB - OBJECTIVES: Using two waves of panel data from the China Health and Retirement Longitudinal Study, this study prospectively assessed whether four distinct patterns of productive activity engagement would predict depressive symptoms among older adults in urban China two years later. METHODS: A sample of urban residents aged 60 or above at Wave 1 and who were interviewed in both waves (N = 2398) was used. Latent class analysis (LCA) was conducted to identify distinct patterns of productive activity engagement that occurred within the Wave 1 data. Next, the generalized estimating equations were used to assess whether identified patterns predicted the levels of depressive symptoms measured at Wave 2. RESULTS: Our use of LCA confirmed the existence of four distinct patterns of productive activity engagement among the study sample: Informal Helper/Carer, Working-Caring Engager, Civic Contributor, and Low/Spousal Carer. All of these three patterns exhibited significantly lower levels of depressive symptoms than that of Low/Spousal Carer two years later. CONCLUSIONS: Our use of individual-based categorization of productive engagement better captured the reality of older adults performing various productive activities than summative scales of productive activities did and, therefore, provided a more valid clarification of differential well-being outcomes among older adults. PMID- 27392121 TI - Amlodipine treatment of hypertension associates with a decreased dementia risk. AB - Hypertension has been shown to be a risk factor for development of dementia. However, medical treatment of hypertension failed to reduce consistently the risk of dementia. Experimental study pointed to the possibility of difference between different calcium channel blockers (CCB) in their neuro-protective effect. The aim of our study was to evaluate the risk of dementia during treatment of hypertension with different CCBs. This is a retrospective cohort study based on electronic database of a large public health care organization. Study period was 11 years and it included patients aged 40-75 years old, having diagnosis of hypertension without diagnosis of dementia at the starting point, treated with either single specific CCB (study group) or with other than CCBs antihypertensive medications (control group) for at least 30 months during the study period. A total of 15,664 patients that satisfied these criteria were identified: 3,884 were treated with amlodipine, 2,062 were treated with nifedipine, 609 were treated with lercanidipine, and 9,109 never received CCBs. Dementia developed in 765 (4.9%) patients. Adjusted hazard ratio (HR) for dementia in patients treated with amlodipine, nifedipine, and lercanidipine was 0.60 (p < 0.001), 0.89 (NS), and 0.90 (NS). Decreased adjusted HR of dementia with amlodipine was demonstrated in the patients aged 60 or more (HR 0.61 [0.49-0.77], p < 0.001), but not in the patients aged less than 60 years old. This study shows that amlodipine therapy may be associated with a decreased dementia risk in hypertensive individuals older than 60 years, compared to those treated without CCBs. PMID- 27392122 TI - Polyaniline/Carbon Nitride Nanosheets Composite Hydrogel: A Separation-Free and High-Efficient Photocatalyst with 3D Hierarchical Structure. AB - A polyaniline (PANI)/carbon nitride nanosheets (CNNS) composite hydrogel with 3D hierarchical nanostructure is synthesized via in situ polymerization. The 3D hierarchical structure is robust and stable, making the composite hydrogel separation-free and easy to recycling. It is highly excellent in removing organic pollutant for PANI/CNNS composite hydrogel on account of the cooperation of adsorptive preconcentration and the following photocatalytic oxidation. Pollutants are first adsorbed and concentrated into the 3D hierarchical nanostructure of the composite hydrogel. Then the pollutants are in situ oxidized via photocatalysis. The promoted photocatalytic performance can be mainly ascribed to the outstanding interfacial charge separation and photoelectrochemical performance. A new idea of the construction of 3D hierarchical photocatalysts is presented, which can be applied in the sustainability field. PMID- 27392123 TI - Frequency and outcome of pediatric acute lymphoblastic leukemia with ZNF384 gene rearrangements including a novel translocation resulting in an ARID1B/ZNF384 gene fusion. AB - BACKGROUND: ZNF384 gene rearrangements with multiple partner genes are recurrent in acute leukemia and are most often associated with a precursor B cell immunophenotype. The overall incidence of this genetic category of leukemia is uncertain. PROCEDURE: Patients with ZNF384 gene rearrangements from a cohort of 240 precursor B cell acute lymphoblastic leukemia (ALL) pediatric patients over a 3.5-year time period were characterized with detailed cytogenetic, FISH, genomic, and clinical analyses. RESULTS: Seven of the 240 patients were identified to have ZNF384 gene rearrangements including partner genes TCF3 (four patients), EWSR1 (one patient), EP300 (one patient), and the novel gene partner ARID1B (one patient). The translocations were confirmed by FISH analysis and with RNA sequencing for the EP300 and ARID1B partner genes. Genomic microarray analysis showed an average of 2.7 copy number alterations in each case with no evidence of imbalance at the translocation breakpoints. Six of the patients with ZNF384 gene rearrangements had precursor B cell ALL with a CD10- immunophenotype and myeloid associated antigens. One of the patients also had myeloperoxidase expression and was diagnosed as mixed phenotype B/myeloid acute leukemia. None of the patients have relapsed with event-free survival ranging from 6 years 2 months to 9 years 2 months. CONCLUSIONS: This study suggests that the frequency of ZNF384 gene rearrangement in pediatric precursor B cell ALL is approximately 3%. The ARID1B gene, commonly mutated in multiple types of cancer, was identified as an additional ZNF384 gene fusion partner. PMID- 27392124 TI - Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats. AB - There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain. PMID- 27392125 TI - Musculoskeletal pain and re-employment among unemployed job seekers: a three-year follow-up study. AB - BACKGROUND: Poor health is a potential risk factor for not finding employment among unemployed individuals. We investigated the associations between localized and multiple-site musculoskeletal pain and re-employment in a three-year follow up of unemployed job seekers. METHODS: Unemployed people (n = 539) from six localities in southern Finland who participated in various active labour market policy measures at baseline in 2002/2003 were recruited into a three-year health service intervention trial. A questionnaire was used to collect data on musculoskeletal health and background characteristics at baseline and on employment status at the end of the follow-up. We conducted a complete case (n = 284) and multiple imputation analyses using logistic regression to investigate the association between baseline musculoskeletal pain and re-employment after three years. RESULTS: Participants with severe pain in the lower back were less likely to become re-employed. This was independent of potential confounding variables. Pain in the hands/upper extremities, neck/shoulders, lower extremities, as well as multiple site were not determinants of re-employment. CONCLUSIONS: Our findings lend some support to the hypothesis that poor health can potentially cause health selection into employment. There is the need to disentangle health problems in order to clearly appreciate their putative impact on employment. This will allow for more targeted interventions for the unemployed. PMID- 27392126 TI - Cancer in patients with schizophrenia: What is the next step? AB - People with schizophrenia, who constitute approximately 0.3-1% of the general population, have a nearly 20% shorter life expectancy than the general population. The incidence of varied types of cancers in patients with schizophrenia is controversial. The majority of previous research has demonstrated that patients who have schizophrenia and cancer have early mortality compared to the general population with cancer. The causes of early mortality in patients with schizophrenia and cancer might be attributed to a lower cancer screening rate and lack of effective treatment, including: (i) patient factors, such as poor lifestyle, passive attitude toward treatment, or comorbidity; (ii) physician factors, such as physician bias, which may decrease the delivery of care for individuals with mental disorders; and (iii) hospital administration factors, such as stigma and discrimination. Additional studies on patients with schizophrenia and cancer are warranted and should include the following: a comprehensive review of previous studies; a focus on differentiating the specific types of cancer; and methods for improvement. To decrease the early mortality of patients with schizophrenia, the following measures are proposed: (i) enhance early detection and early treatment, such as increasing the cancer screening rate for patients with schizophrenia; (ii) provide effective, timely treatment and rehabilitation; (iii) improve patients' psychiatric symptoms and cognitive impairment; (iv) promote healthy behavior in the general population and emphasize healthy lifestyles in vulnerable populations; and (v) remove the stigma of schizophrenia. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this group of patients. PMID- 27392127 TI - The fifth element (of Lucy's sacrum): Reply to Machnicki, Lovejoy, and Reno. PMID- 27392129 TI - Mammary gland and radiation: Knowns and unknowns. AB - Effective breast cancer management and decreasing breast cancer fatalities is contingent upon reliable diagnostic procedures and treatment modalities, including those based on ionizing radiation. On the one hand, ionizing radiation is widely used for cancer diagnostics and therapy, on the other hand it is genotoxic cancer-causing agent. Here we discuss recent studies on the effects of low (diagnostic) and high (treatment) doses of ionizing radiation on healthy breast cells, breast cancer cells, and cancer cells resistant to common drug therapies. PMID- 27392130 TI - From Psychiatry to Flower Power and Back Again: The Amazing Story of Lysergic Acid Diethylamide. AB - Among the psychedelic drugs that enjoyed a period of popularity in psychiatric research during the 1950s and 1960s, lysergic acid diethylamide (LSD) is the most prominent one. Psychiatrists of that time had seen LSD not only as a tool for psychotherapy but also as a potential therapeutic for anxiety, depression, alcohol abuse, autism, and even schizophrenia. When it became a quasi-religious epitome of the Hippie counterculture in the mid 1960s, and cases of what we now call hallucinogen persisting perception disorder and acute psychotic "flashbacks" mounted, authorities moved to make LSD illegal. Although research was never actually forbidden, the field almost completely dried out until the early 2010s. Using today's tools of molecular pharmacology, functional imaging, and neuronal network theory, neuropsychiatry is now resurrecting LSD research-with implications that leave us with many medical and ethical questions. Few people are aware that this is a repurposed compound, originally developed in an effort to synthesize a new analeptic. On top of all potential LSD might have in psychiatry, it also serves as a reminder of the unexpected potential that discarded early-stage compounds can have. PMID- 27392128 TI - CATALISE: A Multinational and Multidisciplinary Delphi Consensus Study. Identifying Language Impairments in Children. AB - Delayed or impaired language development is a common developmental concern, yet there is little agreement about the criteria used to identify and classify language impairments in children. Children's language difficulties are at the interface between education, medicine and the allied professions, who may all adopt different approaches to conceptualising them. Our goal in this study was to use an online Delphi technique to see whether it was possible to achieve consensus among professionals on appropriate criteria for identifying children who might benefit from specialist services. We recruited a panel of 59 experts representing ten disciplines (including education, psychology, speech-language therapy/pathology, paediatrics and child psychiatry) from English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom and USA). The starting point for round 1 was a set of 46 statements based on articles and commentaries in a special issue of a journal focusing on this topic. Panel members rated each statement for both relevance and validity on a seven-point scale, and added free text comments. These responses were synthesised by the first two authors, who then removed, combined or modified items with a view to improving consensus. The resulting set of statements was returned to the panel for a second evaluation (round 2). Consensus (percentage reporting 'agree' or 'strongly agree') was at least 80 percent for 24 of 27 round 2 statements, though many respondents qualified their response with written comments. These were again synthesised by the first two authors. The resulting consensus statement is reported here, with additional summary of relevant evidence, and a concluding commentary on residual disagreements and gaps in the evidence base. PMID- 27392131 TI - Atopic dermatitis, atopic eczema, or eczema? A systematic review, meta-analysis, and recommendation for uniform use of 'atopic dermatitis'. AB - BACKGROUND: The lack of standardized nomenclature for atopic dermatitis (AD) creates unnecessary confusion for patients, healthcare providers, and researchers. It also negatively impacts accurate communication of research in the scientific literature. We sought to determine the most commonly used terms for AD. METHODS: A systematic review of the MEDLINE, EMBASE, and LILACS (1945-2016) for the terms AD, atopic eczema (AE), and multiple other eczematous disorders. RESULTS: In MEDLINE, 33 060 were identified, of which 21 299 (64.4%) publications used the term 'AD', 15 510 (46.9%) 'eczema', and only 2471 (7.5%) AE. Most of these publications used the term AD (82.0%) or eczema (70.8%) without additional nomenclature; only 1.2% used AE alone. Few publications used the terminology 'childhood eczema', 'flexural eczema', 'infantile eczema', 'atopic neurodermatitis', or 'Besnier's prurigo'. AD was rarely used until the late 1970s, after which it became the most commonly used of the three terms and continuously increased until 2015. Atopic eczema decreased between 2008 and 2015. Atopic dermatitis was the most commonly used term in studies across almost all publication types, languages, and journals. CONCLUSION: Atopic dermatitis is the most commonly used term and appears to be increasing in popularity. Given that eczema is a nonspecific term that describes the morphological appearance of several forms of dermatitis, we strongly suggest the use of a more specific term, AD, in publications, healthcare clinician training, and patient education. Support from researchers, reviewers, and editors is key to success. PMID- 27392133 TI - An Iron-Catalyzed Bond-Making/Bond-Breaking Cascade Merges Cycloisomerization and Cross-Coupling Chemistry. AB - Treatment of readily available enynes with alkyl-Grignard reagents in the presence of catalytic amounts of Fe(acac)3 engenders a remarkably facile and efficient reaction cascade that results in the net formation of two new C-C bonds while a C-Z bond in the substrate backbone is broken. Not only does this new manifold lend itself to the extrusion of heteroelements (Z=O, NR), but it can even be used for the cleavage of activated C-C bonds. The reaction likely proceeds via metallacyclic intermediates, the iron center of which gains ate character before reductive elimination occurs. The overall transformation represents a previously unknown merger of cycloisomerization and cross-coupling chemistry. It provides ready access to highly functionalized 1,3-dienes comprising a stereodefined tetrasubstituted alkene unit, which are difficult to make by conventional means. PMID- 27392132 TI - Four Distinct Subgroups of Self-Injurious Behavior among Chinese Adolescents: Findings from a Latent Class Analysis. AB - Self-injurious behavior (SIB) among adolescents is an important public health issue worldwide. It is still uncertain whether homogeneous subgroups of SIB can be identified and whether constellations of SIBs can co-occur due to the high heterogeneity of these behaviors. In this study, a cross-sectional study was conducted on a large school-based sample and latent class analysis was performed (n = 10,069, mean age = 15 years) to identify SIB classes based on 11 indicators falling under direct SIB (DSIB), indirect SIB (ISIB), and suicide attempts (SAs). Social and psychological characteristics of each subgroup were examined after controlling for age and gender. Results showed that a four-class model best fit the data and each class had a distinct pattern of co-occurrence of SIBs and external measures. Class 4 (the baseline/normative group, 65.3%) had a low probability of SIB. Class 3 (severe SIB group, 3.9%) had a high probability of SIB and the poorest social and psychological status. Class 1 (DSIB+SA group, 14.2%) had similar scores for external variables compared to class 3, and included a majority of girls [odds ratio (OR) = 1.94]. Class 2 (ISIB group, 16.6%) displayed moderate endorsement of ISIB items, and had a majority of boys and older adolescents (OR = 1.51). These findings suggest that SIB is a heterogeneous entity, but it may be best explained by four homogenous subgroups that display quantitative and qualitative differences. Findings in this study will improve our understanding on SIB and may facilitate the prevention and treatment of SIB. PMID- 27392134 TI - Fatal Case of West Nile Neuroinvasive Disease in Bulgaria. PMID- 27392135 TI - Electronic Absorption Spectra of Tetrapyrrole-Based Pigments via TD-DFT: A Reduced Orbital Space Study. AB - Tetrapyrrole-based pigments play a crucial role in photosynthesis as principal light absorbers in light-harvesting chemical systems. As such, accurate theoretical descriptions of the electronic absorption spectra of these pigments will aid in the proper description and understanding of the overall photophysics of photosynthesis. In this work, time-dependent density functional theory (TD DFT) at the CAM-B3LYP/6-31G* level of theory is employed to produce the theoretical absorption spectra of several tetrapyrrole-based pigments. However, the application of TD-DFT to large systems with several hundreds of atoms can become computationally prohibitive. Therefore, in this study, TD-DFT calculations with reduced orbital spaces (ROSs) that exclude portions of occupied and virtual orbitals are pursued as a viable, computationally cost-effective alternative to conventional TD-DFT calculations. The effects of reducing orbital space size on theoretical spectra are qualitatively and quantitatively described, and both conventional and ROS results are benchmarked against experimental absorption spectra of various tetrapyrrole-based pigments. The orbital reduction approach is also applied to a large natural pigment assembly that comprises the principal light-absorbing component of the reaction center in purple bacteria. Overall, we find that TD-DFT calculations with proper and judicious orbital space reductions can adequately reproduce conventional, full orbital space, TD-DFT results of all pigments studied in this work. PMID- 27392136 TI - Lack of harms from community-based melanoma screening by primary care providers. PMID- 27392138 TI - High rate of inter-observer agreement between professional-rated scores of the Villalta scale for the assessment of the post-thrombotic syndrome. PMID- 27392137 TI - Cocaine cardiovascular effects and pharmacokinetics after treatment with the acetylcholinesterase inhibitor donepezil. AB - BACKGROUND: In rodents, cholinesterase inhibitors can cause sustained decreases in the reinforcing effects of cocaine. Nonetheless, cocaine is metabolized by butyrylcholinesterase (BuChE), raising concerns that cholinesterase inhibition could increase its peripheral concentrations, perhaps augmenting toxicity. Although donepezil is approved for use in patients and selective for inhibiting acetylcholinesterase over BuChE, no studies have reported cocaine bioavailability in human subjects receiving donepezil. METHODS: Twelve cocaine-dependent veterans received three days of treatment with either oral placebo or 5 mg daily of donepezil, followed by cross-over to the opposite treatment. During both oral treatments, double-blind intravenous cocaine was administered at .0, .18, and .36 mg/kg in a laboratory setting, followed by determinations of heart rate, blood pressure, and plasma concentrations of cocaine and major metabolites. RESULTS: Intravenous cocaine produced dose-related increases in systolic blood pressure that were most pronounced over the initial 30 minutes after treatment. Oral donepezil attenuated drug-induced elevations of systolic blood pressure following low-dose cocaine (.18 mg/kg). No significant difference in blood pressure following treatment with placebo or donepezil after high-dose cocaine (.36 mg/kg). Peak values of blood pressure and heart rate were unaffected by donepezil. Plasma concentrations of cocaine and metabolites did not differ in donepezil- and placebo-treated participants. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: We conclude that donepezil can attenuate drug-induced increases in systolic blood pressure following low-dose cocaine, but does not otherwise modify the cardiovascular effects of intravenous cocaine. Clinically significant changes in cocaine bioavailability and cardiovascular effects do not occur following this dose of donepezil. (Am J Addict 2016;25:392-399). PMID- 27392139 TI - Risk factors for fecal carriage of carbapenemase producing Enterobacteriaceae among intensive care unit patients from a tertiary care center in India. AB - BACKGROUND: Resistance amongst the commensal flora is a serious threat because a very highly populated ecosystem like the gut, may at a later stage, be a source of extra intestinal infections, resistant strains may spread to other host or transfer genetic resistance element to other members of micro-biota including pathogens. This study was carried out to assess fecal colonization by carbapenemase producing Enterobacteriaceae (CPE) and associated risk factors among 100 patients admitted to intensive care unit (ICU). The phenotypic and molecular characterizations of CPE were also included. RESULTS: Colonization with CPE was observed in 6.6 % (8/122) controls. Among ICU patients, fecal carriage of CPE was significantly higher on day 4 (D4) (22 %) as compared to day 1 (D1) (11 %) (p value 0.002). The carbapenemase genes detected included OXA- 48, 181, KPC and NDM-1 with NDM-1 being the predominant carbapenemase in both ICU D1 and D4. Among the 50 CPE isolates, 8 (16 %) were susceptible to meropenem and imipenem (Minimum inhibitory concentration; MIC <= 1 mg/L) and all were susceptible to colistin (MIC range 0.125 - 1 mg/L) and tigecycline (MIC range 0.06- 1.5 mg/L). The risk factors associated with CPE carriage were duration of ICU stay, use of ventilator and aminoglycosides. CONCLUSIONS: Prior colonization with CPE could result in their influx and spread in ICU, challenging infection control measures. Exposure to ICU further increases risk of colonization with diverse carbapenemase producing Enterobacteriaceae. Gut colonization with these strains may be a source of endogenous infection and horizontal transfer of these genes in future. PMID- 27392140 TI - Ageing impact on the transfer factor of 137Cs and 90Sr to lettuce and winter wheat. AB - The study focuses on long-term (extending from 1 to 10 years) lysimeter experiments of the transfer factor of 137Cs and 90Sr to lettuce and winter wheat crops. Transfer factors (Fvs) were the ratio of the activity concentrations of the radionuclides in crops to those in soil, both as dry weight (Bq kg-1). Fvs of 137Cs to lettuce decreased significantly with ageing; geometric means for the 1st, 2nd and 10th year contaminated soil were 0.114, 0.030 and 0.013, respectively. However, a significant decline of Fvs for 137Cs was only seen between the 1st and 2nd year for both wheat compartments (straw and grains) which disappeared thereafter. The dynamic of 137Cs Fvs may be explained according to the distribution coefficient experiment (Kd) which had a value of 3600 L kg-1 showing a high affinity of the clay minerals for caesium. Desorption data revealed that Cs fixation enhanced with ageing. The mechanism involved may be an initial sorption of caesium species to the surface soil particles followed by progressive irreversible fixation to the interlayer of the porous clay minerals. Fvs of 90Sr were high and showed trivial variation for both crops for the time course studied. Sorption of Sr2+ species to the clay mineral may be the governing process, which was supported by high desorption percentage (ranged 77%) with low Kd, i.e. 10 L kg-1. In general, higher Fvs of 137Cs and 90Sr for lettuce was observed in comparison to winter wheat. The diversity of plant species and root systems would play essential roles for such behaviours. PMID- 27392141 TI - Myocardial infarction induced by oral terazosin in a patient with predisposing structural cardiomyopathy: case report. AB - We describe a 71-year-old male patient who developed acute myocardial infarction (AMI) due to a dynamic left ventricular outflow tract obstruction induced by terazosin. After receiving terazosin, the patient had a syncope followed by angina. The electrocardiogram showed Q waves and ST segment elevation in the precordial and inferior leads. Coronary angiography evidenced a chronically occluded left anterior descending artery. Doppler-echocardiography revealed apical akinesia, hyperdynamic basal segments, systolic anterior motion of the mitral valve (SAM) and dynamic left ventricular outflow tract obstruction. Therapy with intravenous fluids and atenolol resulted in marked clinical improvement. Acute myocardial infarction resulted from low coronary perfusion pressure in a patient with a chronically diminished coronary reserve. PMID- 27392142 TI - Heat Shock Factor 1: From Fire Chief to Crowd-Control Specialist. AB - HSF1 is the supposed master regulator of the heat shock response. In this issue of Molecular Cell, Solis et al. reveal that it has a much narrower job description: organizing a small team of molecular chaperones that keep the proteome moving. PMID- 27392143 TI - Persister Awakening. AB - In this issue of Molecular Cell, Cheverton et al. (2016) report that Samonella toxin TacT contributes to persister formation by acetylating tRNA, a novel mechanism of toxin action. Hydrolyzing corrupted tRNA resuscitates persisters. PMID- 27392144 TI - Length Matters: MINDY Is a New Deubiquitinase Family that Preferentially Cleaves Long Polyubiquitin Chains. AB - Abdul Rehman and colleagues identify a sixth family of deubiquitinase enzymes that are highly conserved throughout eukaryotes and show a remarkable selectivity for cleaving extended Lys-48-linked polyubiquitin chains. PMID- 27392147 TI - A Mutant Form of MeCP2 Protein Associated with Human Rett Syndrome Cannot Be Displaced from Methylated DNA by Notch in Xenopus Embryos. PMID- 27392148 TI - Retraction Notice to: Lysyl Oxidase-like 2 Deaminates Lysine 4 in Histone H3. PMID- 27392145 TI - Nuclear Noncoding RNAs and Genome Stability. AB - In modern molecular biology, RNA has emerged as a versatile macromolecule capable of mediating an astonishing number of biological functions beyond its role as a transient messenger of genetic information. The recent discovery and functional analyses of new classes of noncoding RNAs (ncRNAs) have revealed their widespread use in many pathways, including several in the nucleus. This Review focuses on the mechanisms by which nuclear ncRNAs directly contribute to the maintenance of genome stability. We discuss how ncRNAs inhibit spurious recombination among repetitive DNA elements, repress mobilization of transposable elements (TEs), template or bridge DNA double-strand breaks (DSBs) during repair, and direct developmentally regulated genome rearrangements in some ciliates. These studies reveal an unexpected repertoire of mechanisms by which ncRNAs contribute to genome stability and even potentially fuel evolution by acting as templates for genome modification. PMID- 27392146 TI - Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein. AB - Liquid-liquid phase separation, driven by collective interactions among multivalent and intrinsically disordered proteins, is thought to mediate the formation of membrane-less organelles in cells. Using parallel cellular and in vitro assays, we show that the Nephrin intracellular domain (NICD), a disordered protein, drives intracellular phase separation via complex coacervation, whereby the negatively charged NICD co-assembles with positively charged partners to form protein-rich dense liquid droplets. Mutagenesis reveals that the driving force for phase separation depends on the overall amino acid composition and not the precise sequence of NICD. Instead, phase separation is promoted by one or more regions of high negative charge density and aromatic/hydrophobic residues that are distributed across the protein. Many disordered proteins share similar sequence characteristics with NICD, suggesting that complex coacervation may be a widely used mechanism to promote intracellular phase separation. PMID- 27392149 TI - Ebola in Prime Time: A Content Analysis of Sensationalism and Efficacy Information in U.S. Nightly News Coverage of the Ebola Outbreaks. AB - Using a media systems dependency framework, this study looked at media location as a proxy for salience of the Ebola outbreaks in 2014. In unaffected markets where salience was lower, it was hypothesized that news stories would be more sensational and offer less efficacy information as compensation. A total of 1,275 nightly news stories originating from three affected and three unaffected U.S. markets were analyzed. Affected markets were defined as cities where a confirmed case emerged, was treated, or that housed an airport designated as one of the five ports of entry. Unaffected markets did not meet any of these criteria and were not in the same state as any city that did. A statistically significant difference in the average level of sensationalism between the two market types was found (t (1273) = 5.774, p < 0.001), with unaffected markets (M = 0.94, SD = 0.87) having a higher average level of sensationalism than affected markets (M = 0.67, SD = 0.76). There was no statistically significant difference seen in the inclusion of efficacy information between affected and unaffected markets. These findings highlight how specific story elements in news coverage of public health crises may be influenced by media location. PMID- 27392150 TI - Corrigendum: Follower ants in a tandem pair are not always naive. PMID- 27392151 TI - Elevation and latitude interact to drive life-history variation in precocial birds: a comparative analysis using galliformes. AB - Elevational gradients provide a powerful laboratory for understanding the environmental and ecological drivers of geographic variation in avian life history strategies. Environmental variation across elevational gradients is hypothesized to select for a trade-off of reduced fecundity (lower clutch size and/or fewer broods) for higher offspring quality (larger eggs and/or increased parental care) in higher elevation species and populations. In birds, a focus on altricial species from north temperate latitudes has prevented an evaluation of the generality of this trade-off, and how it is affected by latitude and intrinsic factors (development mode). We performed a comparative analysis controlling for body size and phylogenetic relationships on a global data set of 135 galliform species to test (i) whether higher elevation precocial species have lower fecundity (smaller clutch and/or fewer broods) and invest more in offspring quality (greater egg mass) and (ii) whether latitude influences the traits involved and/or the trade-off, and (iii) to identify ecological and environmental drivers of life-history variation along elevational gradients. Life-history traits showed significant interaction effects across elevation and latitude: temperate higher elevation species had smaller clutches and clutch mass, larger eggs and shorter incubation periods, whereas more tropical species had larger clutches, eggs and clutch mass, and longer incubation periods as elevation increased. Number of broods and body mass did not vary with elevation or latitude. Latitudinal gradient in clutch size was observed only for low-elevation species. Significantly, an overlooked latitude-by-elevation interaction confounds our traditional view of clutch size variation across a tropical-to-temperate gradient. Across all latitudes, higher elevation species invested in offspring quality via larger eggs but support for reduced fecundity resulting from smaller clutches was found only along temperate elevational gradients; contrary to expectations, tropical high-elevation species showed increased fecundity. Variation in nest predation risk could explain differences between temperate and tropical elevational gradients, but we lack a consistent mechanism to explain why predation risk should vary in this manner. Alternatively, a resource availability hypothesis based on physical attributes that globally differ between elevation and latitude (seasonality in day length and temperature) seems more plausible. PMID- 27392153 TI - Reduction of Serious Adverse Events Demanding Study Exclusion in Model Development: Extracorporeal Life Support Resuscitation of Ventricular Fibrillation Cardiac Arrest in Rats. AB - Extracorporeal life support is a promising concept for selected patients in refractory cardiogenic shock and for advanced life support of persistent ventricular fibrillation cardiac arrest. Animal models of ventricular fibrillation cardiac arrest could help to investigate new treatment strategies for successful resuscitation. Associated procedural pitfalls in establishing a rat model of extracorporeal life support resuscitation need to be replaced, refined, reduced, and reported.Anesthetized male Sprague-Dawley rats (350-600 g) (n = 126) underwent cardiac arrest induced with a pacing catheter placed into the right ventricle via a jugular cannula. Rats were resuscitated with extracorporeal life support, mechanical ventilation, defibrillation, and medication. Catheter and cannula explantation was performed if restoration of spontaneous circulation was achieved. All observed serious adverse events (SAEs) occurring in each of the experimental phases were analyzed.Restoration of spontaneous circulation could be achieved in 68 of 126 rats (54%); SAEs were observed in 76 (60%) experiments. Experimental procedures related SAEs were 62 (82%) and avoidable human errors were 14 (18%). The most common serious adverse events were caused by insertion or explantation of the venous bypass cannula and resulted in lethal bleeding, cannula dislocation, or air embolism.Establishing an extracorporeal life support model in rats has confronted us with technical challenges. Even advancements in small animal critical care management over the years delivered by an experienced team and technical modifications were not able to totally avoid such serious adverse events. Replacement, refinement, and reduction reports of serious adverse events demanding study exclusions to avoid animal resources are missing and are presented hereby. PMID- 27392152 TI - Induction of aromatic amino acids and phenylpropanoid compounds in Scrophularia striata Boiss. cell culture in response to chitosan-induced oxidative stress. AB - Manipulation of cell culture media by elicitors is one of most important strategies to inducing secondary metabolism for the production of valuable metabolites. In this investigation, inducing effect of chitosan on physiological, biochemical, and molecular parameters were investigated in cell suspension cultures of Scrophularia striata Boiss. The results showed that chitosan concentration and time of elicitation are determinants of the effectiveness of the elicitor. Accumulation of aromatic amino acids (phenylalanine [Phe] and tyrosine [Tyr]), phenylpropanoid compounds (phenolic acids [PAs] and echinacoside [ECH]), hydrogen peroxide (H2O2) production, phenylalanine ammonia-lyase (PAL) activity and gene expression, and antioxidant enzymes (superoxide dismutase [SOD], peroxidase [POX], catalase [CAT]) activities were altered by changing the exposure time of elicitation. Results showed that, upon elicitation with chitosan, oxidative events were induced, antioxidant responses of S. striata cells were boosted through enhanced activity of an effective series of scavenging enzymes (SOD, CAT, and POX), and biosynthesis of non-enzymatic antioxidants (ECH and PAs [cinnamic, p-coumaric and, caffeic acids]). The increase in amino acid content and PAL activity at early days of exposure to chitosan was related with rises in phenolic compounds. These results provide evidence that chitosan by up regulation of PAL gene differentially improves the production of phenylpropanoid compounds, which are of medical commercial value with good biotechnological prospects. PMID- 27392154 TI - The Harmful Effects of Hypertonic Sodium Lactate Administration in Hyperdynamic Septic Shock. AB - Hypertonic sodium lactate (HTL) expands intravascular volume and may provide an alternative substrate for cellular metabolism in sepsis. We compared the effects of HTL, hypertonic saline (HTS), 0.9% ("normal") saline (NS) and Ringer's lactate (RL) on hemodynamics, sublingual and renal microcirculation, renal, mesenteric and brain perfusion, renal and cerebral metabolism, and survival in anesthetized, mechanically ventilated, adult female sheep. Animals (7 in each group) were randomized to receive a bolus (over 15-min) of 3 mL/kg 0.5 M HTL, 3 mL/kg 3% HTS, 10.8 mL/kg NS, or 10.8 mL/kg RL at 2, 6, and 10 h after induction of fecal peritonitis, followed by 2-h infusions of 1 mL/kg/h (HTL/HTS groups) or 3.6 mL/kg/h (NS/RL groups). Animals also received RL and hydroxyethyl starch (ratio 1:1) titrated to maintain pulmonary artery occlusion pressure at baseline levels throughout the experiment. Animals were observed until their spontaneous death. Fluid balance was lower in the HTL and HTS groups than in the other groups from 4 h. Hemodynamic variables were similar among groups during the first 12 h, but thereafter the HTL group had more pronounced decreases in blood pressure and cardiac function. Sublingual and renal microcirculatory abnormalities occurred earlier in the HTL group. Kidney and brain perfusion decreased more rapidly in the HTL group. Median survival times were significantly shorter in the HTL (17 h) and NS (16 h) groups than in the HTS (22 h) or RL (20 h) groups (P = 0.0029). In conclusion, in an ovine model of septic shock, administration of HTL was associated with earlier onset impaired tissue perfusion and shorter survival time. These observations raise concerns about use of HTL in septic shock. PMID- 27392155 TI - Closed-Loop Control of FiO2 Rapidly Identifies Need For Rescue Ventilation and Reduces ARDS Severity in a Conscious Sheep Model of Burn and Smoke Inhalation Injury. AB - : Pulmonary injury can be characterized by an increased need for fraction of inspired oxygen or inspired oxygen percentage (FiO2) to maintain arterial blood saturation of oxygenation (SaO2). We tested a smart oxygenation system (SOS) that uses the activity of a closed-loop control FiO2 algorithm (CLC-FiO2) to rapidly assess acute respiratory distress syndrome (ARDS) severity so that rescue ventilation (RscVent) can be initiated earlier. After baseline data, a pulse oximeter (noninvasive saturation of peripheral oxygenation [SpO2]) was placed. Sheep were then subjected to burn and smoke inhalation injury and followed for 48 h. Initially, sheep were spontaneously ventilating and then randomized to standard of care (SOC) (n = 6), in which RscVent began when partial pressure of oxygen (PaO2) < 90 mmHg or FiO2 < 0.6, versus SOS (n = 7), software that incorporates and displays SpO2, CLC-FiO2, and SpO2/CLC-FiO2 ratio, at which RscVent was initiated when ratio threshold < 250. RscVent was achieved using a G5 Hamilton ventilator (Bonaduz, Switzerland) with adaptive pressure ventilation and adaptive support ventilation modes for SOC and SOS, respectively. OUTCOMES: the time difference from when SpO2/FiO2 < 250 to RscVent initiation was 4.7 +/- 0.6 h and 0.2 +/- 0.1 h, SOC and SOS, respectively (P < 0.001). Oxygen responsiveness after RscVent, defined as SpO2/FiO2 > 250 occurred in 4/7, SOS and 0/7, SOC. At 48 h the SpO2/FiO2 ratio was 104 +/- 5 in SOC versus 228 +/- 59 in SOS (P = 0.036). Ventilatory compliance and peak airway pressures were significantly improved with SOS versus SOC (P < 0.001). Data suggest that SOS software, e.g. SpO2/CLC-FiO2 ratio, after experimental ARDS can provide a novel continuous index of pulmonary function that is apparent before other clinical symptoms. Earlier initiation of RscVent translates into improved oxygenation (reduces ARDS severity) and ventilation. PMID- 27392156 TI - Identification of New Fungal Peroxisomal Matrix Proteins and Revision of the PTS1 Consensus. AB - The peroxisomal targeting signal type 1 (PTS1) is a seemingly simple peptide sequence at the C-terminal end of most peroxisomal matrix proteins. PTS1 can be described as a tripeptide with the consensus motif [S/A/C] [K/R/H] L. However, this description is neither necessary nor sufficient. It does not cover all cases of PTS1 proteins, and some proteins in accordance with this consensus do not target to the peroxisome. In order to find new PTS proteins in yeast and to arrive at a more complete description of the PTS1 consensus motif, we developed a machine learning approach that involves orthologue expansion of the set of known peroxisomal proteins. We performed a genome-wide in silico screen, characterised several PTS1-containing peptides and identified two new peroxisomal matrix proteins, which we named Pxp1 (Yel020c) and Pxp2 (Yjr111c). Based on these in silico and in vivo analyses, we revised the yeast PTS1 consensus which now includes all known PTS1 proteins. PMID- 27392157 TI - Metal dust exposure and lung function deterioration among steel workers: an exposure-response relationship. AB - BACKGROUND: Metallic dust is a heterogeneous substance with respiratory sensitizing properties. Its long term exposure adversely affected lung function, thus may cause acute or chronic respiratory diseases. METHODS: A cross-sectional study was conducted in a steel factory in Terengganu, Malaysia to assess the metal dust exposure and its relationship to lung function values among 184 workers. Metal dust concentrations values (Co, Cr, and Ni) for each worker were collected using air personal sampling. Lung function values (FEV1, FVC, and %FEV1/FVC) were determined using spirometer. RESULTS: Exposure to cobalt and chromium were 1-3 times higher than permissible exposure limit (PEL) while nickel was not exceeding the PEL. Cumulative of chromium was the predictor to all lung function values (FEV1, FVC, and %FEV1/FVC). Frequency of using mask was positively associated with FVC (Adj b = 0.263, P = 0.011) while past respiratory illnesses were negatively associated with %FEV1/FVC (Adj b = -1.452, P = 0.026). Only few workers (36.4%) were found to wear their masks all times during the working hours. CONCLUSIONS: There was an exposure-response relationship of cumulative metal dust exposure with the deterioration of lung function values. Improvement of control measures as well as proper and efficient use or personal protection equipment while at work could help to protect the respiratory health of workers. PMID- 27392158 TI - Direct Measurement of Tissue Oxygenation as a Method of Diagnosis of Acute Compartment Syndrome. AB - OBJECTIVE: The aim of this study was to investigate the utility of direct measurement of tissue oxygenation during compartment syndrome (CS) and tourniquet induced ischemia in a large animal model. We hypothesize that as compartment pressure (CP) rises, circulation within the compartment will decrease resulting in a decreased level of oxygen in the muscle. METHODS: This study used a dog model of both CS- and tourniquet-based ischemia. In 15 animals, CS was induced in 1 hind limb with varying degrees of severity using an infusion model. Tourniquet ischemia was induced in the contralateral hind limb for varying durations. The partial pressure of oxygen (PmO2) was continuously monitored using a polarographic oxygen probe in the muscle of both hind limbs. CP was monitored in the CS limb. PmO2 and CP were analyzed after fasciotomy, performed after approximately 7 hours of warm ischemia, or release of tourniquet. RESULTS: With the application of tourniquet ischemia, PmO2 fell from 38.40 to 1.30 mm Hg (P < 0.001) and subsequently rose after release of the tourniquet to 39.81 mm Hg (P < 0.001). Elevated CP induced by infusion was relieved by fasciotomy (52.04-11.37 mm Hg postfasciotomy, P < 0.001). PmO2 readings in the infusion model were significantly higher in pre-CS than during CS (31.77 mm Hg vs. 3.88 mm Hg, P < 0.001) and rebounded after fasciotomy (50.24 mm Hg, P < 0.001), consistent with hyperemic response. CONCLUSIONS: Increased CP caused an observable decrease in PmO2 that was reversed by fasciotomy. PmO2 can be directly measured in real time with a polarographic tissue pO2 probe. This study is the first step of evaluating an alternative method for diagnosing acute CS. PMID- 27392160 TI - An Evaluation of the OTA-OFC System in Clinical Practice: A Multi-Center Study With 90 Days Outcomes. AB - OBJECTIVES: The purpose of this study is to evaluate the predictive ability of the Orthopedic Trauma-Open Fracture Classification (OTA-OFC) system in regards to short-term (90 days) outcomes of amputation, infection necessitating intravenous antibiotics, and wound healing in clinical practice across multiple centers. DESIGN: Prospective observational study. SETTING: Academic and private practice. PATIENTS/PARTICIPANTS: Patients with open fractures. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: OTA-OFC, amputations, IV antibiotics, and wound healing. RESULTS: Three hundred seventy-three patients with a total of 419 open fractures were enrolled. Logistic regression to predict amputation demonstrated that arterial and skin injury were statistically significant contributors to the prediction of amputation. Bone loss and muscle injury were significant contributors to the prediction of readmission for IV antibiotics. None of the variables in the OTA-OFC were significant predictors of unhealed wounds. CONCLUSION: Our study demonstrates the predictive value of the OTA-OFC regarding the short-term (90 days) outcomes of amputation and infection necessitating IV antibiotics and is another step towards the validation of the OTA-OFC in widespread clinical practice. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 27392162 TI - Invited Commentary: Trauma Center Growth in the United States-A Plea for Planning and Oversight. PMID- 27392161 TI - Extensor Digitorum Brevis Flap for the Coverage of Ankle and Dorsal Foot Wounds: A Technical Trick. AB - Soft tissue wounds overlying the dorsum of the foot and ankle are difficult to treat, and historically have been treated with free tissue transfer. Advances in surgical technique have expanded the use of pedicle perforator flaps to avoid free tissue transfer in certain situations. The authors describe a technique for using an extensor digitorum brevis flap to provide soft tissue coverage for wounds of the ankle and foot. In the senior authors' experience, the use of this flap has achieved wound coverage in 100% of patients with smaller wounds (<=45 cm) of the ankle. PMID- 27392164 TI - Abstracts of the ISPD 20th International Conference on Prenatal Diagnosis and Therapy Berlin, Germany 10-13 July 2016. PMID- 27392163 TI - Adsorption of NO2 on WSe2: DFT and photoelectron spectroscopy studies. AB - The electronic structure modifications of WSe2 upon NO2-adsorption at room and low temperatures were studied by means of photoelectron spectroscopy. We found only moderate changes in the electronic structure, which are manifested as an upward shift of the WSe2-related bands to the smaller binding energies. The observed effects are modelled within the density functional theory approach, where a small adsorption energy of gas molecules on the surface of WSe2 was deduced. The obtained experimental data are explained as a valence bands polarisation effect, which causes their energy shift depending on the adsorption geometry and the formed dipole moment. PMID- 27392165 TI - Investigation on fragmentation pathways of bisphenols by using electrospray ionization Orbitrap mass spectrometry. AB - RATIONALE: Bisphenols, such as bisphenol A (BPA) and bisphenol S (BPS), are widely used in industrial products, although they have been demonstrated to be environmental contaminants with toxicity. However, few studies on the mass spectrometric fragmentation pathway of these compounds have been reported using high-resolution mass spectrometry (HRMS). METHODS: The MS/MS fragmentations of nine bisphenols, together with several corresponding isotope-labeled compounds, were studied by Orbitrap MS using electrospray ionization (ESI) in negative ion mode and higher energy collisional-dissociation (HCD). The [M - H](-) ions of the compounds formed by ESI were selected as the precursor ions for MS/MS. The accurate m/z values for product ions were acquired to deduce the elemental compositions and fragmentation pathways. RESULTS: The elemental compositions of the ions were calculated from the accurate mass data. Common MS/MS product ions and characteristic neutral losses were summarized. Six bisphenols formed the common product ion at m/z 93 (C6 H5 O). The [M - H](-) ions of five bisphenols were found to lose a phenol group (C6 H5 OH). Four bisphenols formed the [M - H - CH4 ](-) ion. The proposed fragmentation pathways of representative compounds of BPA and BPS were verified from the analysis of isotope-labeled compounds. CONCLUSIONS: The MS/MS fragmentation pathways of nine bisphenols were, for the first time, systematically investigated with HRMS. The obtained data could be valuable for the identification of a variety of bisphenols in environmental and biological samples. PMID- 27392166 TI - Effects of rivaroxaban on routine coagulation screening tests using commonly used reagents. PMID- 27392167 TI - An Analysis of the Recruitment and Participation of African American Men in Type 2 Diabetes Self-Management Research: A Review of the Published Literature. AB - Research studies have shown that African American men have experienced higher rates of serious complications of type 2 diabetes, due in part to poor disease management. Although type 2 diabetes research among minority populations is consistently advancing, there still remains a scarcity of African American male representation within these studies. It is unclear if this scarcity stems from lack of interest among men, location of recruitment, or ways in which these men are motivated to participate in research studies. As a result, an analysis of recruitment methods and locations of literature that includes African American men with type 2 diabetes is needed. The purpose of this review of the literature is threefold: (a) determine the number of published empirical studies specific to type 2 diabetes self-management that included African Americans in the sample, (b) to evaluate the percentage of men that were represented in the study sample as compared to how many women, and PMID- 27392169 TI - Correction to: J Interferon Cytokine Res 32(8):368-377. PMID- 27392168 TI - Immunisation coverage among adolescents in a Swiss juvenile correctional facility. PMID- 27392170 TI - Cell lineage responses to photobiomodulation therapy. AB - Photobiomodulation (PBM) therapy has been noted to promote cell proliferation and growth in many different cell types shown both in vitro and in vivo. Currently, treatment regimens are used in the clinic for a variety of ailments, including wound healing. However, most protocols treat an anatomical site without considering individual cell types constituting the target tissues. This study investigates the maximal dose threshold for oral keratinocyte and fibroblast cell types treated with near-infrared laser therapy. We observed keratinocytes have increased sensitivity to laser irradiances (>0.047 W/cm2 , 300 sec, 14.2 J/cm2 ) compared to the fibroblast cells (>0.057 W/cm2 , 300 sec, 15.1 J/cm2 ) (p < 0.0001). Laser treatments were noted to generate increased reactive oxygen species (ROS) levels in keratinocytes compared to fibroblasts that appeared to inversely correlate with higher basal catalase expression. To validate these observations, melatonin was used to treat keratinocytes to induce catalase activity (p < 0.0001). Increased melatonin-induced catalase levels were noted to significantly improve keratinocyte survival to phototoxic laser doses. These observations suggest that clinical laser dosing should account for differential effects of lasers on individual cell types to improve safety and clinical efficacy of PBM therapy. PMID- 27392171 TI - Thermal stability and decompositions kinetics under non-isothermal conditions of imatinib mesylate alpha form. AB - The thermal decomposition and kinetic parameters of synthetized imatinib mesylate alpha form alpha form were determined by thermogravimetry (TGA/DTG) under non isothermal conditions. The experiments were performed at a 25-940 degrees C temperature range at five different heating rates: 2.5Kmin(-1), 5Kmin(-1), 10Kmin(-1), 15Kmin(-1) and 20Kmin(-1) per minute in a nitrogen atmosphere. Imatinib mesylate alpha form presents one-step mass loss during the degradation process. The thermal stability of the examined material, the melting temperature (Tonset=220.6 degrees C) and DeltaH fusion=-95.74Jg(-1) at a heating rate of 10 degrees Cmin(-1) was established. The values of activation energies have been estimated using Kissinger, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) methods. PMID- 27392172 TI - Comparative analysis of the interaction of capecitabine and gefitinib with human serum albumin using (19)F nuclear magnetic resonance-based approach. AB - Monitoring the interaction between drugs and proteins is critical to understanding drug transport and metabolism underlying pharmacodynamics. The binding capacities to human serum albumin of two anticancer drugs, capecitabine and gefitinib, were compared via an approach combining (19)F NMR, (1)H saturation transfer difference (STD) NMR, circular dichroism and docking simulations. Results showed that the two drugs interaction with human serum albumin caused (19)F NMR signal shifted to different directions. Capecitabine had accurate binding site and higher binding affinity than gefitinib. This study provided fresh insights into ligand-protein interaction and the strength of (19)F NMR approach in biomedical research was well illustrated in this case. PMID- 27392173 TI - A highly sensitive LC-MS/MS method for concurrent determination of sildenafil and rosiglitazone in rat plasma. AB - Patients with pulmonary arterial hypertension (PAH) are currently treated with more than one drug. Sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, and rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) activator, is one of those combinations that could be used in PAH. To monitor the pharmacokinetics of sildenafil in the presence of rosiglitazone, we have developed and validated a sensitive, specific and rapid liquid chromatography tandem mass spectrometric (LC-MS/MS) method. We have used this validated method to study the pharmacokinetics of sildenafil and rosiglitazone after intravenous administration of sildenafil alone or a combination of sildenafil plus rosiglitazone to adult male Sprague-Dawley rats. Sildenafil and rosiglitazone were extracted from plasma by protein precipitation with methanol. With an octadeuterated sildenafil as the internal standard, the drugs were separated via gradient elution using a C18 column and formic acid in methanol or in water as the mobile phase with a flow rate of 0.25mL/min. Both sildenafil and rosiglitazone samples in rat plasma produced linear response, when the concentration ranged between 5 and 1000ng/mL (r(2)>0.99). The pharmacokinetics study suggests that intravenous co-administration rosiglitazone plus sildenafil increases the plasma concentration of sildenafil and extends the drug's elimination half-life. PMID- 27392174 TI - Transmission of Xylella fastidiosa to Grapevine by the Meadow Spittlebug. AB - There is little information available on Xylella fastidiosa transmission by spittlebugs (Hemiptera, Cercopoidea). This group of insect vectors may be of epidemiological relevance in certain diseases, so it is important to better understand the basic parameters of X. fastidiosa transmission by spittlebugs. We used grapevines as a host plant and the aphrophorid Philaenus spumarius as a vector to estimate the effect of plant access time on X. fastidiosa transmission to plants; in addition, bacterial population estimates in the heads of vectors were determined and correlated with plant infection status. Results show that transmission efficiency of X. fastidiosa by P. spumarius increased with plant access time, similarly to insect vectors in another family (Hemiptera, Cicadellidae). Furthermore, a positive correlation between pathogen populations in P. spumarius and transmission to plants was observed. Bacterial populations in insects were one to two orders of magnitude lower than those observed in leafhopper vectors, and population size peaked within 3 days of plant access period. These results suggest that P. spumarius has either a limited number of sites in the foregut that may be colonized, or that fluid dynamics in the mouthparts of these insects is different from that in leafhoppers. Altogether our results indicate that X. fastidiosa transmission by spittlebugs is similar to that by leafhoppers. In addition, the relationship between cell numbers in vectors and plant infection may have under-appreciated consequences to pathogen spread. PMID- 27392175 TI - Detection and Quantification of Bremia lactucae by Spore Trapping and Quantitative PCR. AB - Bremia lactucae is an obligate, oomycete pathogen of lettuce that causes leaf chlorosis and necrosis and adversely affects marketability. The disease has been managed with a combination of host resistance and fungicide applications with success over the years. Fungicide applications are routinely made under the assumption that inoculum is always present during favorable environmental conditions. This approach often leads to fungicide resistance in B. lactucae populations. Detection and quantification of airborne B. lactucae near lettuce crops provides an estimation of the inoculum load, enabling more judicious timing of fungicide applications. We developed a quantitative polymerase chain reaction (qPCR)-based assay using a target sequence in mitochondrial DNA for specific detection of B. lactucae. Validation using amplicon sequencing of DNA from 83 geographically diverse isolates, representing 14 Bremia spp., confirmed that the primers developed for the TaqMan assays are species specific and only amplify templates from B. lactucae. DNA from a single sporangium could be detected at a quantification cycle (Cq) value of 32, and Cq values >35 were considered to be nonspecific. The coefficient of determination (R2) for regression between sporangial density derived from flow cytometry and Cq values derived from the qPCR was 0.86. The assay was deployed using spore traps in the Salinas Valley, where nearly half of U.S. lettuce is produced. The deployment of this sensitive B. lactucae-specific assay resulted in the detection of the pathogen during the 2 week lettuce-free period as well as during the cropping season. These results demonstrate that this assay will be useful for quantifying inoculum load in and around the lettuce fields for the purpose of timing fungicide applications based on inoculum load. PMID- 27392176 TI - Cercospora zeina from Maize in South Africa Exhibits High Genetic Diversity and Lack of Regional Population Differentiation. AB - South Africa is one of the leading maize-producing countries in sub-Saharan Africa. Since the 1980s, Cercospora zeina, a causal agent of gray leaf spot of maize, has become endemic in South Africa, and is responsible for substantial yield reductions. To assess genetic diversity and population structure of C. zeina in South Africa, 369 isolates were collected from commercial maize farms in three provinces (KwaZulu-Natal, Mpumalanga, and North West). These isolates were evaluated with 14 microsatellite markers and species-specific mating type markers that were designed from draft genome sequences of C. zeina isolates from Africa (CMW 25467) and the United States (USPA-4). Sixty alleles were identified across 14 loci, and gene diversity values within each province ranged from 0.18 to 0.35. High levels of gene flow were observed (Nm = 5.51), and in a few cases, identical multilocus haplotypes were found in different provinces. Overall, 242 unique multilocus haplotypes were identified with a low clonal fraction of 34%. No distinct population clusters were identified using STRUCTURE, principal coordinate analysis, or Weir's theta theta statistic. The lack of population differentiation was supported by analysis of molecular variance tests, which indicated that only 2% of the variation was attributed to variability between populations from each province. Mating type ratios of MAT1-1 and MAT1-2 idiomorphs from 335 isolates were not significantly different from a 1:1 ratio in all provinces, which provided evidence for sexual reproduction. The draft genome of C. zeina CMW 25467 exhibited a complete genomic copy of the MAT1-1 idiomorph as well as exonic fragments of MAT genes from both idiomorphs. The high level of gene diversity, shared haplotypes at different geographical locations within South Africa, and presence of both MAT idiomorphs at all sites indicates widespread dispersal of C. zeina between maize fields in the country as well as evidence for sexual recombination. The outcomes of this genome-enabled study are important for disease management since the high diversity has implications for dispersal of fungicide resistance should it emerge and the need for diversified resistance breeding. PMID- 27392177 TI - Lack of Population Structure and Mixed Reproduction Modes in Exserohilum turcicum from South Africa. AB - Exserohilum turcicum is the causal agent of northern corn leaf blight, a destructive foliar disease of maize that results in yield losses worldwide. In South Africa, typical yield losses range from 15 to 30%. Previous studies found high haplotypic diversity with evidence for sexual recombination in E. turcicum populations from tropical climates such as Kenya. However, the population genetic structure and method of reproduction of E. turcicum in South Africa is unknown and, therefore, was investigated. Twelve polymorphic microsatellite markers were screened on 258 E. turcicum isolates from maize collected during 2012 and 2013 from three maize fields in South Africa. A multiplex polymerase chain reaction assay amplifying both mating type idiomorphs was applied to investigate the distribution of mating types. No distinct genetic clusters were observed. Shared haplotypes were identified between isolates separated by distances of up to 762 km, which provided evidence of migration. High haplotypic diversity indicated that sexual reproduction is occurring among E. turcicum isolates, although mating type ratios and linkage disequilibrium analyses did not support the hypothesis of random mating. The population genetic structure of E. turcicum in South Africa is likely due to the direct movement and spread of isolates undergoing a mixed reproductive lifecycle. PMID- 27392178 TI - Soybean Resistance to the Soybean Cyst Nematode Heterodera glycines: An Update. AB - The soybean cyst nematode (SCN), Heterodera glycines, remains a serious threat to soybean production throughout the world. A lack of genetic diversity in resistant soybean cultivars has led to a widespread shift toward virulence in SCN populations, leaving farmers with few proven options other than nonhost rotation to manage this nematode. Recent advances in our understanding of the genes controlling resistance to the nematode have led to improved molecular markers, which are, in turn, increasing the efficiency and precision of the breeding pipeline. A better understanding of the molecular and biochemical basis of SCN resistance and nematode virulence will provide information useful for the development of a long-term strategic plan for diversification and the deployment of cultivars that protect current sources of natural resistance while identifying new targets for engineering novel resistance. PMID- 27392179 TI - Decreased Biosynthesis of Jasmonic Acid via Lipoxygenase Pathway Compromised Caffeine-Induced Resistance to Colletotrichum gloeosporioides Under Elevated CO2 in Tea Seedlings. AB - Caffeine, the major purine alkaloid in tea has long been known for its role in plant defense. However, its effect on Colletotrichum gloeosporioides that causes brown blight disease in tea is largely unknown especially under elevated CO2. Here we show that elevated CO2 reduced endogenous caffeine content in tea leaves, but sharply increased susceptibility of tea to C. gloeosporioides. The expression of C. gloeosporioides actin gene was gradually increased during the postinoculation period. In contrast, foliar application of caffeine decreased the C. gloeosporioides-induced necrotic lesions and the expression of C. gloeosporioides actin. Analysis of endogenous jasmonic acid (JA) content revealed that exogenous caffeine could induce JA content under both CO2 conditions in absence of fungal infection; however, in presence of fungal infection, caffeine increased JA content only under elevated CO2. Furthermore, exogenous caffeine enhanced lipoxygenase (LOX) activity and its biosynthetic gene expression under both CO2 conditions, indicating that increased JA biosynthesis via LOX pathway by caffeine might strengthen plant defense only under elevated CO2, while caffeine induced defense under ambient CO2 might be associated with JA-independent LOX pathway in tea. These results provide novel insights into caffeine-induced plant defense mechanisms that might help to develop an eco-friendly approach for disease control. PMID- 27392180 TI - Analysis of Sequenced Genomes of Xanthomonas perforans Identifies Candidate Targets for Resistance Breeding in Tomato. AB - Bacterial disease management is a challenge for modern agriculture due to rapid changes in pathogen populations. Genome sequences for hosts and pathogens provide detailed information that facilitates effector-based breeding strategies. Tomato genotypes have gene-for-gene resistance to the bacterial spot pathogen Xanthomonas perforans. The bacterial spot populations in Florida shifted from tomato race 3 to 4, such that the corresponding tomato resistance gene no longer recognizes the effector protein AvrXv3. Genome sequencing showed variation in effector profiles among race 4 strains collected in 2006 and 2012 and compared with a race 3 strain collected in 1991. We examined variation in putative targets of resistance among Florida strains of X. perforans collected from 1991 to 2006. Consistent with race change, avrXv3 was present in race 3 strains but nonfunctional in race 4 strains due to multiple independent mutations. Effectors xopJ4 and avrBs2 were unchanged in all strains. The effector avrBsT was absent in race 3 strains collected in the 1990s but present in race 3 strains collected in 2006 and nearly all race 4 strains. These changes in effector profiles suggest that xopJ4 and avrBsT are currently the best targets for resistance breeding against bacterial spot in tomato. PMID- 27392181 TI - Novel Functional Genomics Approaches: A Promising Future in the Combat Against Plant Viruses. AB - Advances in functional genomics and genome editing approaches have provided new opportunities and potential to accelerate plant virus control efforts through modification of host and viral genomes in a precise and predictable manner. Here, we discuss application of RNA-based technologies, including artificial micro RNA, transacting small interfering RNA, and Cas9 (clustered regularly interspaced short palindromic repeat-associated protein 9), which are currently being successfully deployed in generating virus-resistant plants. We further discuss the reverse genetics approach, targeting induced local lesions in genomes (TILLING) and its variant, known as EcoTILLING, that are used in the identification of plant virus recessive resistance gene alleles. In addition to describing specific applications of these technologies in plant virus control, this review discusses their advantages and limitations. PMID- 27392183 TI - The science of vaccine adjuvants: advances in TLR4 ligand adjuvants. AB - TLR ligands are used in modern vaccine adjuvants, TLR4 ligand-based adjuvants are the most advanced in commercial vaccines. Increased understanding of TLR4 receptor-ligand interactions enables chemical synthesis and modification of new leads and our understanding of the biological/immunological mechanisms of combination adjuvants enables formulation of potent and safe vaccine compositions. Characterization of non-glycolipid TLR4 ligands provided new mechanistic information that could lead to new formulations. This review discusses advances in TLR4 agonist design-both glycolipid and non-glycolipid based TLR4 ligands-as well as CD14 activation as options to activate or synergize with TLR4 signaling. Finally, we review the molecular and cellular mechanisms that are elicited by formulated TLR4 targeted combination adjuvants during the initiation of innate immune responses leading to quality adaptive responses. PMID- 27392182 TI - A bivalent pneumococcal histidine triad protein D-choline-binding protein A vaccine elicits functional antibodies that passively protect mice from Streptococcus pneumoniae challenge. AB - Vaccines based on conserved pneumococcal proteins are being investigated because serotype coverage by pneumococcal polysaccharide and polysaccharide conjugate vaccines is incomplete and may eventually decrease due to serotype replacement. Here, we examined the functionality of human antibodies induced by a candidate bivalent choline-binding protein A- pneumococcal histidine triad protein D (PcpA PhtD) vaccine. Pre- and post-immune sera from subjects who had been vaccinated with the PcpA-PhtD candidate vaccine were tested in an established passive protection model in which mice were challenged by intravenous injection with Streptococcus pneumoniae serotype 3 strain A66.1. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial surface binding by serum antibodies was determined by a flow cytometry-based assay. Sera from 20 subjects were selected based on low activity of pre-immune samples in the passive protection model. Bacterial surface binding correlated more strongly with anti-PcpA (0.87; p < 0.0001) than with anti-PhtD (0.71; p < 0.0001). The odds ratio for predicting survival in the passive protection assay was higher for the anti-PcpA concentration (470 [95% confidence interval (CI), 46.8 to >999.9]) than for the anti-PhtD concentration (3.4 [95% CI, 1.9 to 5.6]) or bacterial surface binding (9.4 [95% CI, 3.6 to 24.3]). Pooled post-immune serum also protected mice against a challenge with S. pneumoniae serotype 3 strain WU2. Both anti-PcpA and anti-PhtD antibodies induced by the bivalent candidate vaccine mediate protection against S. pneumoniae. The results also showed that the ELISA titer might be useful as a surrogate for estimating the functional activity of antibodies induced by pneumococcal protein vaccines. PMID- 27392184 TI - Systems biology and the quest for correlates of protection to guide the development of an HIV vaccine. AB - Over the last three decades, a myriad of data has been generated regarding HIV/SIV evolution, immune evasion, immune response, and pathogenesis. Much of this data can be integrated and potentially used to generate a successful vaccine. Although individual approaches have begun to shed light on mechanisms involved in vaccine-conferred protection from infection, true correlates of protection have not yet been identified. The systems biology approach helps unify datasets generated using different techniques and broaden our understanding of HIV immunopathogenesis. Moreover, systems biology is a tool that can provide correlates of protection, which can be targeted for the production of a successful HIV vaccine. PMID- 27392185 TI - [Editor's Comment]. PMID- 27392186 TI - [Transcutaneous laryngeal electromyography]. PMID- 27392187 TI - [Inner Ear Hearing Loss Part II: Sudden Sensorineural Hearing Loss, Therapeutic Options]. AB - The great majority of hearing disorders generates from pathologies in the inner ear, mainly the outer hair cells, as mentioned in the first part of this review. Very often, however, hearing loss appears suddenly and even without external causes like noise exposure. This sudden hearing loss is mostly unilateral, recovers very often spontaneously and should be treated, if persisting. Only in this acute stage there are therapeutic options available. If the inner ear hearing loss is chronic there is no curative therapy, an effective management of the hearing disorder is only possible through rehabilitation. This is due to the fact, that hair cells of all mammals, incl. humans, have no regenerative capacity and neither pharmaceutic agents nor other means can induce regeneration and recovery of hair cells. Even a gen-therapy is not available yet. In the second part of this review the main focus lies in sudden hearing loss and general therapeutic options for inner ear hearing loss. PMID- 27392188 TI - [Smooth Nodular Mass of the Cavum Conchae]. PMID- 27392189 TI - [A Creative Solution for Posterior Epistaxis: The Solothurn One and a Half 10 cm Merocel-Construction]. PMID- 27392190 TI - [From the Expert's Office: The CI-Implantation with Recognized Occupational Hearing Impairment and Following Deafness Irrespective of Noise: Does Health Insurance or Employer's Liability Insurance Coverage have to Take Over the Costs?]. PMID- 27392192 TI - [Not Available]. PMID- 27392193 TI - [Not Available]. PMID- 27392191 TI - [Presbycusis - Age Related Hearing Loss]. AB - Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID- 27392194 TI - Comparison of the effects of three types of aminobutyric acids on the control of Penicillium expansum infection in pear fruit. AB - BACKGROUND: Aminobutyric acids were reported to have inhibitory effects on postharvest fungal diseases. The effects of alpha-aminobutyric acid (AABA), beta aminobutyric acid (BABA) and gamma-aminobutyric acid (GABA) on the control of Penicillium expansum infection in pear fruit were compared in the present study. RESULTS: BABA and GABA reduced the disease incidence of P. expansum infection in pear fruit when applied at an appropriate concentration and with a suitable treatment time. The efficacy of GABA was superior to BABA, whereas AABA had no inhibition effect. Three types of aminobutyric acids almost had no direct antifungal activity against P. expansum in vitro and in vivo, although BABA and GABA inhibited spore germination of P. expansum in vivo at a concentration of 100 mg L-1 when P. expansum was inoculated 24 h after treatment. Moreover, BABA and GABA enhanced catalase activity and all three aminobutyric acids enhanced peroxidase activity in pear fruit after being challenged by P. expansum, although BABA and GABA were more forceful than AABA. CONCLUSION: The position of the amino group in aminobutyric acids may be associated with the effects of aminobutyric acids on the control of postharvest fungal diseases. (c) 2016 Society of Chemical Industry. PMID- 27392195 TI - The role of microaerophilic Fe-oxidizing micro-organisms in producing banded iron formations. AB - Despite the historical and economic significance of banded iron formations (BIFs), we have yet to resolve the formation mechanisms. On modern Earth, neutrophilic microaerophilic Fe-oxidizing micro-organisms (FeOM) produce copious amounts of Fe oxyhydroxides, leading us to wonder whether similar organisms played a role in producing BIFs. To evaluate this, we review the current knowledge of modern microaerophilic FeOM in the context of BIF paleoenvironmental studies. In modern environments wherever Fe(II) and O2 co-exist, microaerophilic FeOM proliferate. These organisms grow in a variety of environments, including the marine water column redoxcline, which is where BIF precursor minerals likely formed. FeOM can grow across a range of O2 concentrations, measured as low as 2 MUm to date, although lower concentrations have not been tested. While some extant FeOM can tolerate high O2 concentrations, many FeOM appear to prefer and thrive at low O2 concentrations (~3-25 MUm). These are similar to the estimated dissolved O2 concentrations in the few hundred million years prior to the 'Great Oxidation Event' (GOE). We compare biotic and abiotic Fe oxidation kinetics in the presence of varying levels of O2 and show that microaerophilic FeOM contribute substantially to Fe oxidation, at rates fast enough to account for BIF deposition. Based on this synthesis, we propose that microaerophilic FeOM were capable of playing a significant role in depositing the largest, most well-known BIFs associated with the GOE, as well as afterward when global O2 levels increased. PMID- 27392196 TI - Practical Lessons Learned from Adolescent and Parent Experiences Immediately and 12 Months following a Family-Based Healthy Lifestyle Intervention. AB - BACKGROUND: Adolescence is a critical time to intervene and establish healthy long-term behaviors to decrease the impact of adult obesity in the future. The purpose of this study was to identify key intervention strategies and techniques for community interventions by analyzing the short-term and longer-term shared experiences of both adolescents with overweight or obesity and their parents involved in a community-based, healthy lifestyle intervention. METHODS: Qualitative interviews and focus groups were conducted with teens (aged 12-16 years with a BMI above the 85th percentile) and their parents immediately following the 8-week intervention (n = 37 teens, n = 33 parents) and at 12 months follow-up (n = 23 teens, n = 20 parents). Results were analyzed thematically. RESULTS: Both teens and parents reported high satisfaction with the program. Immediately following the 8-week intervention, teens reported enjoying participating in exercise with similar peers. Parents described inaccurate expectations from the program. After the 12-month follow-up, teens reported struggling with a cyclical pattern of health behaviors, and parents described a sense of loss following the intensive program and improved communication skills with their adolescent. CONCLUSIONS: Several practical strategies emerged for use in future community programs for adolescents with overweight or obesity. Future programs should consider management of expectations, perceptions vs. outcomes, and the cyclical nature of behavior change in adolescents. Strategies for future health behavior change interventions with overweight adolescents should address time management, translation of knowledge into behavior change, successful implementation of practical goal-setting strategies, and increasing intrinsic motivation. PMID- 27392197 TI - Serum uric acid levels and inflammatory markers with respect to dipping status: A retrospective analysis of hypertensive patients with or without chronic kidney disease. AB - BACKGROUND: The aim of this study was to evaluate serum uric acid levels, inflammatory markers [C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR)] and mean platelet volume (MPV) among hypertensive patients with or without chronic kidney disease (CKD) with respect to dipping status. METHODS: A total of 432 hypertensive patients with (n = 340) or without (n = 92) CKD who had ambulatory blood pressure monitoring recordings were included. Correlation of serum uric acid levels with inflammatory markers (CRP, PLR, NLR) was evaluated as was the logistic regression analysis for determinants of nondipper pattern. RESULTS: Nondipper pattern was noted in 65.2% and 79.7% of non-CKD and CKD patients, respectively. Multivariate logistic regression analysis revealed that only serum uric acid (OR, 2.69; 95% CI, 1.60 to 4.52; p = 0.000), MPV (OR, 1.81; 95% CI, 1.30 to 2.53; p = 0.000), PLR (OR, 0.98; 95% CI, 0.97 to 0.99; p = 0.000), and serum albumin (OR, 0.42; 95% CI, 0.19 to 0.93; p = 0.031) were significant determinants of nondipper pattern in the overall study population. CONCLUSION: In conclusion, our findings revealed higher prevalence of nondipper pattern in hypertensive patients with than without CKD and significantly higher levels for uric acid, CRP, MPV, PLR, and NLR among nondipper than dipper hypertensive patients with CKD. High levels for uric acid and MPV and lower levels for PLR and serum albumin were noted as significant determinants of nondipper pattern among hypertensive patients. PMID- 27392198 TI - Morphology Engineering for High-Performance and Multicolored Perovskite Light Emitting Diodes with Simple Device Structures. AB - The film morphology is extremely significant for solution processed perovskite devices. Through fine morphology engineering without using any additives or further posttreatments, a full-coverage and high quantum yield perovskite film has been achieved based on one-step spin-coating method. The morphologies and film characteristics of MAPbBr3 with different MABr:PbBr2 starting material ratios are in-depth investigated by scanning electron microscopy, atomic force microscopy, X-ray diffraction, photoluminescence, and time resolved photoluminescence. High performance organometal halide perovskite light-emitting didoes (PeLEDs) based on simple device structure of indium tin oxide/poly(3,4 ethylenedioxythiophene):polystyrene sulfonate ( PEDOT: PSS)/perovskite/TPBi/Ca/Al are demonstrated. The green PeLED based on MAPbBr3 shows a maximum luminance of 8794 cd m(-2) (at 7.3 V) and maximum current efficiency of 5.1 cd A(-1) (at 5.1 V). Furthermore, a class of hybrid PeLEDs by adjusting the halide ratios of methylammonium lead halide (MAPbX3 , where X is Cl, Br, or I) are also demonstrated at room temperature. These mix-halogenated PeLEDs show bright luminance (above 100 cd m(-) (2) ) with narrow and clean emission bands over the wide color gamut. PMID- 27392199 TI - Nasal high flow nebulization in infants and toddlers: An in vitro and in vivo scintigraphic study. AB - Aerosol therapy in infants and toddlers is challenging. Nebulization within a nasal high flow (NHF) circuit is attractive. The aim of this study was to quantify aerosol lung deposition when combined with NHF as compared with standard practice. Lung doses were measured scintigraphically after nebulization with jet and mesh nebulizer placed within a NHF circuit in a spontaneously breathing non human primate model (macaque) and in the anatomical bench SAINT model, respectively representing a full-term newborn and a 9-month-old toddler. In the SAINT model, lung depositions observed with the mesh nebulizer placed in the NHF circuit set at 2 and 4 L/min were 3.3% and 4.2% of the nebulizer charge, respectively, and similar to the 1.70% observed with the control standard facemask jet nebulization (6 L/min flow). In the macaque model, the depositions observed with the mesh nebulizer in the NHF circuit set at 2 and 4 L/min were 0.49% and 0.85%, respectively, also similar to the control measurement (0.71%). Mesh nebulization within a NHF circuit set at 8 L/min and jet nebulization either within a NHF circuit or placed on top of the cannula (NHF set at 2 L/min; total flow of 8 L/min), resulted in a significantly lower lung depositions. Mesh nebulization within a NHF circuit delivering up to 4 L/min gas is likely to be at least as effective than jet nebulization with a facemask in infants and toddlers. Aerosol facemask placement on top of cannulas or jet nebulization within the NHF circuit may be less effective. Pediatr Pulmonol. 2017;52:337-344. (c) 2016 Wiley Periodicals, Inc. PMID- 27392200 TI - Cytokines related to three major types of cell-mediated immunity in short- and long-term exposures to lead compounds. AB - Many investigators have posited on the significant influence of lead on the immune system function. However, available data on this topic are not conclusive. Therefore, a study was undertaken to examine associations between lead exposure and levels of cytokines related to the T-helper (TH)-1, TH2, and TH17 types of immune response in humans. For these analyses, three population groups were examined: the first consisted of male workers exposed to lead for a short period of time (36-44 days); the second included male workers chronically exposed to lead (13 +/- 10 years); and a control group that was composed of male administrative workers with blood lead levels (BLL) < 10 MUg/dl. BLL were determined for all study subjects. Thereafter, serum samples were analyzed for the levels of interleukin (IL)-2 (IL-2), IL-4, IL-5, IL-12, IL-13, IL-17A, and interferon (IFN)-gamma using a multi-analyte system. The results indicated that the levels of IFNgamma IL-2, IL-12 (related to TH1 cells), IL-4, IL-5, IL-13 (related to TH2 cells), and IL-17A (related to TH17 cells) did not change after a short-term exposure to lead (compared to baseline). However, the levels of all of these cytokines were significantly higher in workers chronically exposed to lead than in the controls by 82%, 32%, 81%, 22%, 70%, 42%, and 17% (IFNgamma, IL-2, IL 12, IL-4, IL-5, IL-13, IL-17A, respectively). From these studies, we conclude that in humans, a short-term exposure to lead does not affect levels of cytokines related to the TH1-, TH2-, and TH17-mediated immune responses, while chronic exposure modifies their levels. Taken together, these modifications do not evidence an ability of lead to promote specifically one type of immune response in an exposed host. PMID- 27392201 TI - Surface-Adsorbed Long G-Quadruplex Nanowires Formed by G:C Linkages. AB - G-quadruplexes connected into long, continuous nanostructures termed G-wires show properties superior to dsDNA when applied in nanotechnology. Using AFM imaging, we systematically studied surface adsorption of a set of G-rich oligonucleotides with GC-termini for their ability to form long G-wires through G:C pairing. We investigated the effects of increasing sequence length, the type of nucleotide in the side loops, and removal of the CG-3' terminus. We found that sequences with adenine in the side loops most readily form G-wires. The role of magnesium as an efficient surface-anchoring ion was also confirmed. Conversely, as resolved from dynamic light scattering measurements, magnesium had no ability to promote G quadruplex formation in solution. These insights may help in selecting prosperous candidates for construction of G-quadruplex based nanowires and to explore them for their electronic properties. PMID- 27392202 TI - Reply to: Vitamin insufficiencies/deficiencies in relation to sickle cell disease severity and associated morbidity. PMID- 27392203 TI - Gold on Different Manganese Oxides: Ultra-Low-Temperature CO Oxidation over Colloidal Gold Supported on Bulk-MnO2 Nanomaterials. AB - Nanoscopic gold particles have gained very high interest because of their promising catalytic activity for various chemicals reactions. Among these reactions, low-temperature CO oxidation is the most extensively studied one due to its practical relevance in environmental applications and the fundamental problems associated with its very high activity at low temperatures. Gold nanoparticles supported on manganese oxide belong to the most active gold catalysts for CO oxidation. Among a variety of manganese oxides, Mn2O3 is considered to be the most favorable support for gold nanoparticles with respect to catalytic activity. Gold on MnO2 has been shown to be significantly less active than gold on Mn2O3 in previous work. In contrast to these previous studies, in a comprehensive study of gold nanoparticles on different manganese oxides, we developed a gold catalyst on MnO2 nanostructures with extremely high activity. Nanosized gold particles (2-3 nm) were supported on alpha-MnO2 nanowires and mesoporous beta-MnO2 nanowire arrays. The materials were extremely active at very low temperature (-80 degrees C) and also highly stable at 25 degrees C (70 h) under normal conditions for CO oxidation. The specific reaction rate of 2.8 molCO.h(-1).gAu(-1) at a temperature as low as -85 degrees C is almost 30 times higher than that of the most active Au/Mn2O3 catalyst. PMID- 27392204 TI - A noninvasive ultrasound elastography technique for measuring surface waves on the lung. AB - The purpose of this work was to demonstrate an ultrasound based surface wave elastography (SWE) technique for generating and detecting surface waves on the lung. The motivation was to develop a noninvasive technique for assessing superficial lung tissue disease including interstitial lung disease (ILD). ILD comprises a number of lung disorders in which the lung tissue is stiffened and damaged due to fibrosis of the lung tissue. Currently, chest radiographs and computed tomography (CT) are the most common clinical methods for evaluating lung disease, but they are associated with radiation and cannot measure lung mechanical properties. The novelty of SWE is to develop a noninvasive and nonionizing technique to measure the elastic properties of superficial lung tissue. We propose to generate waves on the lung surface through wave propagation from a local harmonic vibration excitation on the chest through an intercostal space. The resulting surface wave propagation on the lung is detected using an ultrasound probe through the intercostal space. To demonstrate that surface waves can be generated on the lung, an ex vivo muscle-lung model was developed to evaluate lung surface wave generation and detection. In this model, swine muscle was laid atop a swine lung. A vibration excitation of 0.1s 100Hz wave was generated on the muscle surface and the surface waves on the lung were detected using a linear array ultrasound probe at 5MHz. To test its feasibility for patient use, SWE was used to measure both lungs of an ILD patient through eight intercostal spaces. The mean wave speed was 1.71+/-0.20m/s (+/-SD) at the functional residual capacity, while the mean wave speed was 2.36+/-0.33m/s at the total lung capacity. These studies support the feasibility of SWE for noninvasive measurement of elastic properties of lung and demonstrate potential for assessment of ILD. PMID- 27392205 TI - Analysis of contributions of nonlinear material constants to temperature-induced velocity shifts of quartz surface acoustic wave resonators. AB - In this paper, we examine the significance of the various higher-order effects regarding calculating temperature behavior from a set of material constants and their temperature coefficients. Temperature-induced velocity shifts have been calculated for quartz surface acoustic wave (SAW) resonators and the contributions of different groups of nonlinear material constants (third-order elastic constants (TOE), third-order piezoelectric constants (TOP), third-order dielectric constants (TOD) and electrostrictive constants (EL)) to the temperature-induced velocity shifts have been analyzed. The analytical methodology has been verified through the comparison of experimental and analytical results for quartz resonators. In general, the third-order elastic constants were found to contribute most significantly to the temperature-induced shifts in the SAW velocity. The contributions from the third-order dielectric constants and electrostrictive constants were found to be negligible. For some specific cases, the third-order piezoelectric constants were found to make a significant contribution to the temperature-induced shifts. The significance of each third-order elastic constant as a contributor to the temperature-velocity effect was analyzed by applying a 10% variation to each of the third-order elastic constants separately. Additionally, we have considered the issues arising from the commonly used thermoelastic expansions that provide a good but not exact description of the temperature effects on frequency in piezoelectric resonators as these commonly used expansions do not include the effects of higher-order material constants. PMID- 27392206 TI - Validation of the Andon KD5031 for clinical use and self-measurement according to the European Society of Hypertension International Protocol. AB - OBJECTIVE: This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure (BP) monitor Andon KD5031 for home BP monitoring according to the European Society of Hypertension International Protocol revision 2010. METHODS: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using the standard mercury sphygmomanometer and the Andon KD5031 device. Ninety-nine pairs of comparisons were obtained from 33 participants for analysis. RESULTS: The KD5031 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10, and 15 mmHg was 66/99, 93/99, and 98/99, respectively, for SBP and 72/99, 94/99, and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. Twenty-six participants for both SBP and DBP had at least two of the three device-observer differences within 5 mmHg (required >=24). The number of participants without a device-observer difference within 5 mmHg was one for SBP and three for DBP (required <=3). CONCLUSION: The Andon upper arm BP monitor KD5031 has passed the International Protocol requirements, and it can be recommended for clinical use and self-measurement in adults. PMID- 27392207 TI - Synthesis of Aminobenzoic Acid Derivatives via Chemoselective Carbene Insertion into the -NH Bond Catalyzed by Cu(I) Complex. AB - Phosphine ligand stabilized air-stable Cu(I) complexes have been successfully used to functionalize the aromatic aminobenzoic acids in a chemoselective manner without implementing protection and deprotection strategy under mild reaction conditions. This chemoselective carbene insertion into -NH bond over -COOH and OH bonds leads to the wide range of carboxy and hydroxy functionalized alpha amino esters (27 examples). All of the isolated new products have been fully characterized using standard analytical methods. PMID- 27392208 TI - CNT-Confinement Effects on the Menshutkin SN2 Reaction: The Role of Nonbonded Interactions. AB - We investigated the effects of CNT confinement ((6,6) tube) on the model Menshutkin reaction H3N + H3CCl = H3NCH3((+)) + Cl((-)), which is representative of chemical processes involving developing of charge separation along the reaction pathway. We used either a full QM approach or a hybrid QM/MM approach. We found that the CNT significantly lowers the activation barrier with respect to the hypothetical gas-phase reaction: The activation barrier Ea varies from 34.6 to 25.7 kcal mol(-1) (a value similar to that found in a nonpolar solvent) and the endothermicity DeltaE from 31.2 to 13.5 kcal mol(-1). A complex interplay between C-H...pi, N-H...pi, and Cl...pi nonbonded interactions of the endohedral system with the CNT wall explains the lower barrier and lower endothermicity. The hybrid QM/MM approach (MM = UFF force field) does not reproduce satisfactorily the QM energy DeltaE (18.1 vs 13.5 kcal mol(-1)), while optimum agreement is found in the barrier Ea (25.8 vs 25.7 kcal mol(-1)). These results suggest that the simple Qeq formalism (included in the MM potential) does not describe properly the effect of CNT polarization in the presence of the net charge separation featuring the final product. A more accurate estimate of the tube polarization was obtained with single-point QM/MM computations including PCM corrections (using the benzene dielectric constant) on the QM/MM optimized structures. After PCM corrections, Ea changes slightly (from 25.8 to 24.5 kcal mol(-1)), but a more significant variation is observed for DeltaE that becomes 13.1 kcal mol(-1), in rather good agreement with the full QM. This level of theory (QM/MM with PCM correction, MM = UFF) represents a more general approach suitable for describing CNT-confined chemical processes involving significant charge separation. QM/MM computations were extended to CNTs of different radii: (4,4), (5,5), (7,7), (8,8), (9,9), (10,10), (12,12), (14,14) CNTs and, as a limit case, a graphene sheet. The lack of space available in the small tube (4,4) causes a strong structural distortion and a consequent increase in Ea and DeltaE (40.8 and 44.0 kcal mol(-1), respectively). These quantities suddenly decrease with the augmented volume inside the (5,5) tube. For larger tubes, different structural arrangements of the endohedral system are possible, and Ea and DeltaE remain almost constant until the limiting case of graphene. PMID- 27392209 TI - Usefulness of CBCL/6-18 to evaluate emotional and behavioral problems in Indonesian autism spectrum disorder children. AB - BACKGROUND: The Child Behavior Checklist (CBCL) has been widely utilized to estimate emotional and behavioral problems in children in the USA and Europe. Although the Indonesian version of the CBCL/6-18 was proven to have good validity and internal consistency in children with typical development (TD) in Indonesia, it has not been utilized for children with autism spectrum disorder (ASD). The purpose of this study was therefore to investigate the usefulness of CBCL/6-18 for detecting emotional and behavioral problems in Indonesian ASD children. METHODS: One hundred and eight mothers of children with ASD and with TD were enrolled in this study. The diagnosis of ASD in Indonesia was made by expert child neurologists based on DSM-IV-TR. Mothers of children aged 6-18 years completed the Indonesian version of the CBCL. RESULTS: The scores of total problems, internalizing, and externalizing were significantly higher in the ASD group than the TD group. Children with ASD scored significantly higher in seven of the eight CBCL subscales (except somatic complaints) compared with TD children. CONCLUSIONS: The CBCL/6-18 Indonesian version could be considered as a useful tool for detecting emotional and behavioral problems in children with ASD in Indonesia in Muslim populations. PMID- 27392210 TI - Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral centre. AB - RATIONALE: The European Position Paper on Sinusitis (EPOS) guidelines provide composite criteria to evaluate chronic rhinosinusitis (CRS) control, taking into consideration the severity of patients' symptoms, aspect of nasal mucosa and medical intake as parameters of CRS control. OBJECTIVES: To study the degree of CRS control using novel EPOS control criteria at 3-5 years after a functional endoscopic sinus surgery (FESS) and correlate these data to symptoms scores. METHODS: Adult CRS patients (n = 560) who had undergone bilateral FESS for chronic inflammatory sinonasal disease 3-5 years prior to the study were included. Patients received a postal questionnaire asking for control items according to EPOS control criteria, visual analogue scale (VAS) scores for total and individual sinonasal symptoms, sinonasal outcome test (SNOT)-22 and Short Form (SF)-36 questionnaires. MEASUREMENTS AND MAIN RESULTS: About 19.5% of CRS patients were well controlled, with 36.8% of patients being partly controlled and 43.7% uncontrolled. The levels of control corresponded to mean total VAS, SNOT-22 and SF-36 scores. Subgroup analysis revealed that female gender, aspirin intolerance and revision FESS were associated with higher prevalence of uncontrolled CRS, whereas allergy, asthma and smoking status did not alter the percentage of patients in each category of control. In 81 patients attending the outpatient clinic, nasal endoscopy changed classification in only four patients (4.9%). CONCLUSIONS: Based on the novel EPOS control criteria, at least 40% of CRS patients are uncontrolled at 3-5 years after FESS. Therefore, better treatment strategies leading to higher disease control are warranted in CRS care. PMID- 27392211 TI - Sequence-Specific Incorporation of Enzyme-Nucleotide Chimera by DNA Polymerases. AB - DNA polymerases select the right nucleotide for the growing polynucleotide chain based on the shape and geometry of the nascent nucleotide pairs and thereby ensure high DNA replication selectivity. High-fidelity DNA polymerases are believed to possess tight active sites that allow little deviation from the canonical structures. However, DNA polymerases are known to use nucleotides with small modifications as substrates, which is key for numerous core biotechnology applications. We show that even high-fidelity DNA polymerases are capable of efficiently using nucleotide chimera modified with a large protein like horseradish peroxidase as substrates for template-dependent DNA synthesis, despite this "cargo" being more than 100-fold larger than the natural substrates. We exploited this capability for the development of systems that enable naked-eye detection of DNA and RNA at single nucleotide resolution. PMID- 27392212 TI - Reducing Children's Implicit Racial Bias Through Exposure to Positive Out-Group Exemplars. AB - Studies with adults suggest that implicit preferences favoring White versus Black individuals can be reduced through exposure to positive Black exemplars. However, it remains unclear whether developmental differences exist in the capacity for these biases to be changed. This study included 369 children and examined whether their implicit racial bias would be reduced following exposure to positive Black exemplars. Results showed that children's implicit pro-White bias was reduced following exposure to positive Black exemplars, but only for older children (Mage = ~10 years). Younger children's (Mage = ~7 years) implicit bias was not affected by this intervention. These results suggest developmental differences in the malleability of implicit racial biases and point to possible age differences in intervention effectiveness. PMID- 25353639 TI - Is pentoxifylline effective in alcoholic hepatitis? ?First update. AB - ABOUT THE UPDATE: This article updates the June 2014 Living FRISBEE (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos). It incorporates a new systematic review identifying one study not included in previous reviews. The new evidence leads to substantial changes in the existing evidence. ASBTRACT: Pentoxifylline is an inhibitor of tumor necrosis factor, and has been proposed as treatment for alcoholic hepatitis. However, it is not clear if it is effective, or if it adds benefit to the treatment with corticosteroids. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including eight randomized controlled trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded pentoxifylline probably leads to little or no difference in mortality in alcoholic hepatitis. PMID- 27392214 TI - "You don't know what's wrong with you": an exploration of cancer-related experiences in people with an intellectual disability. AB - OBJECTIVE: Few empirical studies have explored cancer-related experiences of people with an intellectual disability (ID), despite rising cancer incidence in this population. The present research aims to better understand the experiences of this population from multiple perspectives, generating theory and further research questions. METHODS: Six people with ID and cancer, alongside 12 participants from their supportive network (including family and social and health care professionals), were interviewed; transcripts were analyzed using grounded theory. RESULTS: People with ID were often overlooked within cancer consultations and excluded from conversations about their care and treatment related decisions. Caregivers (family and paid) were relied upon to facilitate communication and understanding and supplement health care professional knowledge. Caregivers' attempts to protect the patient from distress harmed communication further; our interviewees suggest that increased involvement and empowerment mediated cancer-related distress. Where health care professionals possessed good patient-centered skills, and additional support was offered, people with ID were more likely to engage meaningfully in their cancer-related experience. CONCLUSIONS: Interestingly, emergent concepts were consistent with general psycho-oncology literature; however, incidence and severity of difficulty was substantially greater in this sample. This disparity warrants further exploration, with a need for intervention research to develop effective ways of supporting health care professionals in enhancing patient-centered skills with this population. In the clinical setting, patient involvement in health care decisions (despite problems associated with comorbidity) is imperative to optimize engagement. PMID- 27392215 TI - The Emergence of Synaesthesia in a Neuronal Network Model via Changes in Perceptual Sensitivity and Plasticity. AB - Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own. To explore the conditions under which synaesthesia evolves, we studied a neuronal network model that represents two recurrently connected neural systems. The interactions in the network evolve according to learning rules that optimize sensory sensitivity. We demonstrate several scenarios, such as sensory deprivation or heightened plasticity, under which synaesthesia can evolve even though the inputs to the two systems are statistically independent and the initial cross-talk interactions are zero. Sensory deprivation is the known causal mechanism for acquired synaesthesia and increased plasticity is implicated in developmental synaesthesia. The model unifies different causes of synaesthesia within a single theoretical framework and repositions synaesthesia not as some quirk of aberrant connectivity, but rather as a functional brain state that can emerge as a consequence of optimising sensory information processing. PMID- 27392216 TI - Hair cortisol and cortisone are decreased by natural sunlight. AB - BACKGROUND AND AIMS: Hair glucocorticoids (cortisol and cortisone) are increasingly used as measures of long-term integrated exposure to glucocorticoid hormones. Glucocorticoids gradually disappear from the hair shaft, which may result from exposure to ultraviolet (UV) radiation in natural sunlight. We aimed to study the influence of sun exposure on hair glucocorticoids. MATERIAL AND METHODS: Scalp hair samples were obtained from nine volunteers (median age 33 [range 21-81], 7 females), and part of each hair sample was exposed to three experimental conditions: repeated exposure to natural sunlight for 40h (natural UV), exposure to a high amount of artificial UV radiation, and storage in the dark (control). Hair cortisol (HairF) and cortisone (HairE) were quantified by liquid chromatography-tandem mass spectrometry. RESULTS: When compared to control, HairF was decreased in 9 out of 9 hair samples after natural sunlight exposure (median decrease -3.1pg/mg or -54%, P<0.001) and artificial UV radiation (-4.7pg/mg or -75%, P=0.003). HairE decreased in 8 out of 9 samples, both after natural sunlight (-7.6pg/mg or -32%, P=0.012) and artificial UV (-10.7pg/mg or 52%, P=0.026). CONCLUSIONS: Exposure to natural sunlight decreases the glucocorticoid content of scalp hair, apparently through UV radiation, and is therefore an important confounder that should be considered in studies involving the measurement of hair glucocorticoids. PMID- 27392217 TI - Burning Fat Fuels Leukemic Stem Cell Heterogeneity. AB - Obese leukemia patients exhibit reduced survival after chemotherapy, suggesting an important role of adipose tissue in disease progression. In this issue of Cell Stem Cell, Ye et al. (2016) reveal metabolic heterogeneity in leukemic stem cell (LSC) subpopulations and show that chemotherapy-resistant CD36+ LSCs co-opt gonadal adipose tissue to support their metabolism and survival. PMID- 27392218 TI - Metabolic RemodeLIN of Pluripotency. AB - Cellular metabolism is a key regulator of cell fate, including fate in pluripotent stem cells. Now in Cell Stem Cell, Zhang et al. (2016) show that Lin28 controls the metabolic transition from naive to primed pluripotency by directly repressing oxidative metabolism genes and metabolic intermediates involved in epigenetic regulation independently of let-7. PMID- 27392219 TI - Modeling Zika Virus Infection in Mice. AB - Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly. PMID- 27392220 TI - Eliminating Cancer Stem Cells in CML with Combination Transcriptional Therapy. AB - Leukemia stem cells (LSCs) are resistant to current therapies used to treat chronic myeloid leukemia (CML). Abraham et al. (2016) have identified a molecular network critical for CML LSC survival and propose that simultaneously targeting two of their major transcriptional regulators, p53 and c-Myc, may facilitate their eradication. PMID- 27392221 TI - Fate by Chance, not by Choice: Epidermal Stem Cells Go Live. AB - The skin epidermis is constantly renewed by epidermal stem cells. In a recent Science paper, Rompolas et al. utilize live imaging to track epidermal stem cells over their lifetimes. Their findings provide new insights into epidermal stem cell behaviors and unravel how newly generated cells are integrated into pre existing tissues. PMID- 27392222 TI - 10 Questions: Approaches to Research Funding. AB - We asked four stem cell scientists who recently started their labs or expanded their research programs to share their insights and approaches to obtaining funding. We present highlights from their interview responses here. PMID- 27392223 TI - Policy Implications of Aging in the NIH-Funded Workforce. AB - Because of national interest in the "graying" of the biomedical workforce, we examine aging and funding within the pool of NIH-funded investigators and applicants, particularly in the growing field of stem cell research. We provide evidence of a maturing and more competitive stem cell workforce and discuss policy implications. PMID- 27392224 TI - CIRM and UKRMP: Different Ways to Invest in Regenerative Medicine. AB - The California Institute for Regenerative Medicine (CIRM) and the UK Regenerative Medicine Platform (UKRMP) have similar objectives, but their histories, funding mechanisms, and governance could hardly be more different. Here, we compare the two programs and explore their impact in translating stem cell research into clinical applications. PMID- 27392225 TI - Chromium isotopic composition of core-top planktonic foraminifera. AB - The chromium isotope system (53 Cr/52 Cr expressed as delta53 Cr relative to NIST SRM 979) is potentially a powerful proxy for the redox state of the ocean atmosphere system, but a lack of temporally continuous, well-calibrated archives has limited its application to date. Marine carbonates could potentially serve as a common and continuous Cr isotope archive. Here, we present the first evaluation of planktonic foraminiferal calcite as an archive of seawater delta53 Cr. We show that single foraminiferal species from globally distributed core tops yielded variable delta53 Cr, ranging from 0.10/00 to 2.50/00. These values do not match with the existing measurements of seawater delta53 Cr. Further, within a single core-top, species with similar water column distributions (i.e., depth habitats) yielded variable delta53 Cr values. In addition, mixed layer and thermocline species do not consistently exhibit decreasing trends in delta53 Cr as expected based on current understanding of Cr cycling in the ocean. These observations suggest that either seawater delta53 Cr is more heterogeneous than previously thought or that there is significant and species-dependent Cr isotope fractionation during foraminiferal calcification. Given that the delta53 Cr variability is comparable to that observed in geological samples throughout Earth's history, interpreting planktonic foraminiferal delta53 Cr without calibrating modern foraminifera further, and without additional seawater measurements, would lead to erroneous conclusions. Our core-top survey clearly indicates that planktonic foraminifera are not a straightforward delta53 Cr archive and should not be used to study marine redox evolution without additional study. It likewise cautions against the use of delta53 Cr in bulk carbonate or other biogenic archives pending further work on vital effects and the geographic heterogeneity of the Cr isotope composition of seawater. PMID- 27392226 TI - Biomechanical investigation into the structural design of porous additive manufactured cages using numerical and experimental approaches. AB - Traditional solid cages have been widely used in posterior lumbar interbody fusion (PLIF) surgery. However, solid cages significantly affect the loading mechanism of the human spine due to their extremely high structural stiffness. Previous studies proposed and investigated porous additive manufactured (AM) cages; however, their biomechanical performances were analyzed using oversimplified bone-implant numerical models. Thus, the aim of this study was to investigate the outer shape and inner porous structure of the AM cages. The outer shape of the AM cages was discovered using a simulation-based genetic algorithm; their inner porous structure was subsequently analyzed parametrically using T10 S1 multilevel spine models. Finally, six types of the AM cages, which were manufactured using selective laser melting, were tested to validate the numerical outcomes. The subsidence resistance of the optimum design was superior to the conventional cage designs. A porous AM cage with a pillar diameter of 0.4mm, a pillar angle of 40 degrees , and a porosity of between 69% and 80% revealed better biomechanical performances. Both the numerical and experimental outcomes can help surgeons to understand the biomechanics of PLIF surgery combined with the use of AM cages. PMID- 27392227 TI - Predictive modeling of colorectal cancer using a dedicated pre-processing pipeline on routine electronic medical records. AB - Over the past years, research utilizing routine care data extracted from Electronic Medical Records (EMRs) has increased tremendously. Yet there are no straightforward, standardized strategies for pre-processing these data. We propose a dedicated medical pre-processing pipeline aimed at taking on many problems and opportunities contained within EMR data, such as their temporal, inaccurate and incomplete nature. The pipeline is demonstrated on a dataset of routinely recorded data in general practice EMRs of over 260,000 patients, in which the occurrence of colorectal cancer (CRC) is predicted using various machine learning techniques (i.e., CART, LR, RF) and subsets of the data. CRC is a common type of cancer, of which early detection has proven to be important yet challenging. The results are threefold. First, the predictive models generated using our pipeline reconfirmed known predictors and identified new, medically plausible, predictors derived from the cardiovascular and metabolic disease domain, validating the pipeline's effectiveness. Second, the difference between the best model generated by the data-driven subset (AUC 0.891) and the best model generated by the current state of the art hypothesis-driven subset (AUC 0.864) is statistically significant at the 95% confidence interval level. Third, the pipeline itself is highly generic and independent of the specific disease targeted and the EMR used. In conclusion, the application of established machine learning techniques in combination with the proposed pipeline on EMRs has great potential to enhance disease prediction, and hence early detection and intervention in medical practice. PMID- 27392228 TI - The degree of heart rate asymmetry is crucial for the validity of the deceleration and acceleration capacity indices of heart rate: A model-based study. AB - The deceleration capacity (DC) and acceleration capacity (AC) of heart rate are a pair of indices used for evaluating the autonomic nervous system (ANS). We assessed the role of heart rate asymmetry (HRA) in defining the relative performance of DC and AC using a mathematical model, which is able to generate a realistic RR interval (RRI) time series with controlled ANS states. The simulation produced a set of RRI series with random sympathetic and vagal activities. The multi-scale DCs and ACs were computed from the RRI series, and the correlation of DC and AC with the ANS functions was analyzed to evaluate the performance of the indices. In the model, the HRA level was modified by changing the inspiration/expiration (I/E) ratio to examine the influence of HRA on the performances of DC and AC. The results show that on the conventional scales (T=1, s=2), an HRA level above 50% results in a stronger association of DC with the ANS, compared with AC. On higher scales (T=4, s=6), there was no HRA and DC showed a similar performance to AC for all I/E ratios. The data suggest that the HRA level determines which of DC or AC is the optimal index for expressing ANS functions. Future clinical applications of DC and AC should be accompanied by an HRA analysis to provide a better index for assessing ANS. PMID- 27392229 TI - Overgeneral autobiographical memory at baseline predicts depressive symptoms at follow-up in patients with first-episode depression. AB - Previous studies have shown that overgeneral autobiographical memory (OGM) is a characteristic of depression. However, there are no studies to explore the association between baseline OGM and depressive symptoms at follow-up in patients with first-episode depression (FE). This study investigated whether baseline OGM predicts depressive symptoms at follow-up in patients with FE. We recruited 125 patients with FE. The participants were divided into remitted group and non remitted group according to the severity of their depression at 12 months follow up. The measures consisted of the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Hierarchical linear regression analyses and bootstrap mediation analyses were conducted. The results showed that non-remitted patients had more OGM at baseline. Baseline OGM predicted depressive symptoms at follow-up in patients with FE. Rumination mediated the relationship between baseline OGM and depressive symptoms at follow up. Our findings highlight OGM as a vulnerability factor involved in the maintenance of depression in patients with FE. PMID- 27392230 TI - Neurological soft signs in Chinese adolescents with antisocial personality traits. AB - The current study was designed to explore the specific relationship between neurologic soft signs (NSSs) and characteristics of antisocial personality traits in adolescents, and to investigate particular NSSs linked to certain brain regions in adolescents with antisocial personality traits. The research was conducted on 96 adolescents diagnosed with ASP traits (ASP trait group) using the ASPD subscale of the Personality Diagnostic Questionnaire for the DSM-IV (PDQ-4+) and 96 adolescents without traits of any personality disorder (control group). NSSs were assessed using the soft sign subscales of the Cambridge Neurological Inventory. Adolescents with ASP traits showed more motor coordination, sensory integration, disinhibition, and total NSSs than the control group. Seven NSSs, including stereognosia in right hand, finger agnosia and graphesthesia in both hands, left-right orientation, and go/no go stimulus, were significantly more frequent in teenagers with ASP traits. Sensory integration was positively associated with ASP traits. Adolescents with antisocial personality traits might have abnormalities in the central nervous system, and sensory integration might be the particular indicator of antisocial personality disorder. PMID- 27392231 TI - Childhood trauma and general cognitive ability: Roles of minimization/denial and gender. AB - The aim of this study was to investigate the effects of minimization and gender on the interaction between childhood trauma and general cognitive ability. The study included 345 students. The data were obtained via an information form, the Childhood Trauma Questionnaire (CTQ), and Raven's standard progressive matrices (RSPM). The mean CTQ total score and the mean sexual abuse, physical, and emotional neglect subscale scores of the male students were significantly higher than those of the female students (p<0.05). The mean minimization score of the female students was greater than that of the male students (p<0.05). However, among the female students with minimization scores of 3, there was a moderate and significant negative correlation between the CTQ and RSPM scores (r=-0.533, p<0.05). This study found that general cognitive ability was influenced by childhood trauma among female students with higher minimization/neglect scores. The results of the current study suggest that ignoring the effects of minimization may be a misleading factor for determining the gender ratio of childhood trauma and evaluating its effect on long-term cognitive functions. PMID- 27392232 TI - Combining Neopentyllithium with Potassium tert-Butoxide: Formation of an Alkane Soluble Lochmann-Schlosser Superbase. AB - Mixtures of alkyllithium and heavier alkali-metal alkoxides are often used to form alkyl compounds of heavier alkali metals, but these mixtures are also known for their high reactivity in deprotonative metalation reactions. These organometallic mixtures are often called LiC-KOR superbases, but despite many efforts their constitution remains unknown. Herein we present mixed alkali-metal alkyl/alkoxy compounds produced by reaction of neopentyllithium with potassium tert-butoxide. The key to success was the good solubility and temperature stability of neopentyl alkali-metal compounds, leading to hexane-soluble mixtures, which allowed handling at ambient temperatures and isolation by crystallization. The compounds in solid state and in solution were identified by X-ray crystallography and NMR spectroscopy as mixtures of lithium/potassium neopentyl/tert-butoxy aggregates of varying compositions Lix Ky Npz (OtBu)x+y-z . PMID- 27392233 TI - Fiber optofluidic biosensor for the label-free detection of DNA hybridization and methylation based on an in-line tunable mode coupler. AB - An optical fiber optofluidic biosensor for the detection of DNA hybridization and methylation has been proposed and experimentally demonstrated. An in-line fiber Michelson interferometer was formed in the photonic crystal fiber. A micrhole in the collapsed region, which combined the tunable mode coupler and optofluidic channel, was fabricated by using femtosecond laser micromachining. The mode field diameter of the guided light is changed with the refractive index in the optofluidic channel, which results in the tunable coupling ratio. Label-free detections of the DNA hybridization and methylation have been experimentally demonstrated. The probe single stranded DNA (ssDNA) was bound with the surface of the optofluidic channel through the Poly-l-lysine layer, and the hybridization between a short 22-mer probe ssDNA and a complementary target ssDNA was carried out and detected by interrogating the fringe visibility of the reflection spectrum. Then, the DNA methylation was also detected through the binding between the methylated DNA and the 5-methylcytosine (5-mC) monoclonal antibody. The experiments results demonstrate that the limit of detection of 5nM is achieved, establishing the tunable mode coupler as a sensitive and versatile biosensor. The sensitive optical fiber optofluidic biosensor possesses high specificity and low temperature cross-sensitivity. PMID- 27392234 TI - Electrosynthesis and binding properties of molecularly imprinted poly-o phenylenediamine for selective recognition and direct electrochemical detection of myoglobin. AB - Electrosynthesis of molecularly imprinted polymer (MIP) templated with myoglobin (Mb) and the reference non-imprinted polymer (NIP) was examined with o phenylenediamine (o-PD) as a monomer. Mass-sensitive quartz crystal microbalance with dissipation monitoring supplied by an electrochemical module (EQCM-D) was applied to characterize and optimize MIP/NIP electrosynthesis. Mb rebinding was detected by direct electrocatalytic reduction of Mb by square wave voltammetry (SWV) or differential pulse voltammetry (DPV). The results obtained showed high specificity of polymeric antibodies to template Mb, with an imprinting factor determined as a ratio Imax(MIP)/Imax(NIP) of 2-4. The prepared MIP sensor is characterized by an apparent dissociation constant of (3.3+/-0.5)*10(-9)M and has a broad range of working concentrations of 1nM-1MUM, with the detection limit of 0.5nM (9ng/ml). Mb rebinding was examined in Mb-free diluted human serum spiked with Mb as well as in plasma samples of patients with acute myocardial infarction (AMI) and in control plasma of healthy donors in order to demonstrate the potential medical application of developed MIP sensors. PMID- 27392235 TI - Ultrasensitive electrochemical sensing platform for microRNA based on tungsten oxide-graphene composites coupling with catalyzed hairpin assembly target recycling and enzyme signal amplification. AB - An ultrasensitive electrochemical biosensor for microRNA (miRNA) is developed based on tungsten oxide-graphene composites coupling with catalyzed hairpin assembly target recycling and enzyme signal amplification. WO3-Gr is prepared by a simple hydrothermal method and then coupled with gold nanoparticles to act as a sensing platform. The thiol-terminated capture probe H1 is immobilized on electrode through Au-S interaction. In the presence of target miRNA, H1 opens its hairpin structure by hybridization with target miRNA. This hybridization can be displaced from the structure by another stable biotinylated hairpin DNA (H2), and target miRNA is released back to the sample solution for next cycle. Thus, a large amount of H1-H2 duplex is produced after the cyclic process. At this point, a lot of signal indicators streptavidin-conjugated alkaline phosphatase (SA-ALP) are immobilized on the electrode by the specific binding of avidin-biotin. Then, thousands of ascorbic acid, which is the enzymatic product of ALP, induces the electrochemical-chemical-chemical redox cycling to produce a strongly electrochemical response in the presence of ferrocene methanol and tris (2 carboxyethyl) phosphine. Under the optimal experimental conditions, the established biosensor can detect target miRNA down to 0.05fM (S/N=3) with a linear range from 0.1fM to 100pM, and discriminate target miRNA from mismatched miRNA with a high selectivity. PMID- 27392241 TI - Erratum for: In Vitro Chondroprotective Potential of Extracts Obtained from Various Phyllantus Species. PMID- 27392242 TI - Saponins from Saponaria officinalis L. Augment the Efficacy of a Rituximab Immunotoxin. AB - Triterpenoidal saponins are synthesized in the roots of Saponaria officinalis L. The same plant is also a source for the toxin Saporin, which is a ribosome inactivating protein. Triterpenoidal saponins are known to increase the cytotoxicity of Saporin by modulating its intracellular trafficking. Here, we investigated if the combinatorial effects elicited by purified saponins and Saporin can be applied to increase the therapeutic efficacy of the immunotoxin Saporin-Rituximab. First, saponins were purified by high-performance liquid chromatography. Thereafter, their intrinsic cytotoxicity was evaluated on Ramos cells with no observed effect up to 5 ug/mL, however, saponins increased the cytotoxicity of Saporin, while no influence was observed on its N-glycosidase activity. Saporin-Rituximab bound to CD20 in Ramos cells and, in the absence of saponins, had a GI50 (concentration inhibiting cell growth to 50 %) of 7 nM. However, in the presence of a nontoxic concentration of saponins, the GI50 of Saporin-Rituximab was 0.01 nM, a nearly 700-fold increase in efficacy. Moreover, two further immunotoxins, namely Saporin-anti-CD22 and Saporin-anti-CD25, were tested in combination with saponins yielding enhancement factors of 170-fold and 25-fold, respectively. All three receptors are present in Ramos cells and the differences in cytotoxicity enhancement may be explained by the differing expression levels of the cellular receptors. The application of purified saponins from S. officinalis L. is therefore a new strategy to potentially improve the cytotoxicity and therapeutic efficacy of Rituximab-immunotoxins for the treatment of B-cell lymphoma. PMID- 27392243 TI - Flavonoids from Cyclopia genistoides and Their Xanthine Oxidase Inhibitory Activity. AB - The present paper reports the chemical analysis of the methanolic extracts of fermented and non-fermented Cyclopia genistoides herbs and an investigation of the xanthine oxidase inhibitory activity of the isolated constituents. Chemical analysis of the leaves and stems of C. genistoides yielded the isolation and identification of two benzophenone glucosides, iriflophenone 2-O-beta glucopyranoside (1) and iriflophenone 3-C-beta-glucopyranoside (2), two pterocarpans, (6aR,11aR)-(-)-2-methoxymaackiain (5) and (6aR,11aR)-(-)-maackiain (6), along with the flavanones liquiritigenin (9) and hesperetin (10), the flavone diosmetin (11), the isoflavones afrormosin (7) and formononetin (8), piceol (3), and 4-hydroxybenzaldehid (4). Among the eleven compounds, nine are reported for the first time from this species, and six from the genus Cyclopia. These compounds, together with previously isolated secondary metabolites of this species, were tested for xanthine oxidase inhibitory activity. The 5,7 dihydroxyflavones luteolin and diosmetin significantly inhibited the enzyme in vitro, while hesperetin (10) and 5,7,3',5'-tetrahydroxyflavone exerted weak activity. PMID- 27392244 TI - Phenylethylchromones with In Vitro Antitumor Promoting Activity from Aquilaria filaria. AB - A new chromone, 2-(2-hydroxy-2-phenylethyl)chromone (1), was isolated together with ten known phenylethyl chromones from MeOH extracts of agarwood (Aquilaria filaria). The selected compounds were evaluated in an antiproliferative assay against five human tumor cell lines, including a multidrug-resistant cell line. They were also tested for antitumor promoting activity, as mediated by 12-O tetradecanoylphorbol-13-acetate-induced activation of the Epstein-Barr virus early antigen in Raji cells. Among all compounds, 4',7-dimethyoxy-6 hydroxychromone (2) displayed broad spectrum antiproliferative activity against all tumor cell lines tested with IC50 values of 25-38 uM, while 8 was selectively inhibitory against multidrug-resistant cells. All tested compounds suppressed tumor promotion at noncytotoxic concentrations. 4',6-Dihydroxyphenylethylchromone (7) exhibited the most potent effect with an IC50 value of 319 mol ratio relative to 12-O-tetradecanoylphorbol-13-acetate. This study is the first to report the antitumor promoting activity of 2-(2-phenylethyl)chromone derivatives, as well as the selective antiproliferative activity of 8 against a multidrug-resistant tumor cell line. PMID- 27392245 TI - Arginase Inhibitor 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-Glucoside Activates Endothelial Nitric Oxide Synthase and Improves Vascular Function. AB - Endothelial arginase constrains the activity of endothelial nitric oxide synthase by reducing nitric oxide bioavailability, which contributes to vascular diseases. During screening, we identified a novel compound from the rhizome of Polygonum multiflorum (Polygonaceae), 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), which inhibited arginase activity. THSG exhibited noncompetitive inhibition of arginase II and inhibited both arginases I and II in a dose dependent manner. THSG-dependent arginase inhibition reciprocally increased nitric oxide production and decreased reactive oxygen species generation in aortic endothelia. These effects were associated with increased dimerization of endothelial nitric oxide synthase without changes in the protein expression levels of arginase I, arginase II, or endothelial nitric oxide synthase. In vascular tension assays, when aortic vessels from wild-type mice are incubated with THSG, responses to the nitric oxide-dependent vasorelaxant acetylcholine were augmented, but responses to an nitric oxide donor, sodium nitroprusside, were not affected. On the other hand, phenylephrine-dependent vasoconstriction was significantly retarded in THSG-treated vessels. In a high-cholesterol diet fed atherogenic model mice (ApoE-/-), THSG improved endothelial function by enhancement of the nitric oxide-cGMP pathway. Taken together, these results suggest that THSG may exert vasoprotective effects through augmentation of nitric oxide signaling by inhibiting arginase. Therefore, THSG may be useful in the treatment of vascular diseases that are derived from endothelial dysfunction, such as atherosclerosis. PMID- 27392246 TI - DNA Barcoding for the Identification of Botanicals in Herbal Medicine and Dietary Supplements: Strengths and Limitations. AB - In the past decades, the use of traditional medicine has increased globally, leading to a booming herbal medicine and dietary supplement industry. The increased popularity of herbal products has led to a rise in demand for botanical raw materials. Accurate identification of medicinal herbs is a legal requirement in most countries and prerequisite for delivering a quality product that meets consumer expectations. Traditional identification methods include botanical taxonomy, macroscopic and microscopic examination, and chemical methods. Advances in the identification of biological species using DNA-based techniques have led to the development of a DNA marker-based platform for authentication of plant materials. DNA barcoding, in particular, has been proposed as a means to identify herbal ingredients and to detect adulteration. However, general barcoding techniques using universal primers have been shown to provide mixed results with regard to data accuracy. Further technological advances such as mini-barcodes, digital polymerase chain reaction, and next generation sequencing provide additional tools for the authentication of herbs, and may be successful in identifying processed ingredients used in finished herbal products. This review gives an overview on the strengths and limitations of DNA barcoding techniques for botanical ingredient identification. Based on the available information, we do not recommend the use of universal primers for DNA barcoding of processed plant material as a sole means of species identification, but suggest an approach combining DNA-based methods using genus- or species-specific primers, chemical analysis, and microscopic and macroscopic methods for the successful authentication of botanical ingredients used in the herbal dietary supplement industry. PMID- 27392247 TI - Glycerol metabolism promotes biofilm formation by Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa causes persistent infections in the airways of cystic fibrosis (CF) patients. Airway sputum contains various host-derived nutrients that can be utilized by P. aeruginosa, including phosphotidylcholine, a major component of host cell membranes. Phosphotidylcholine can be degraded by P. aeruginosa to glycerol and fatty acids to increase the availability of glycerol in the CF lung. In this study, we explored the role that glycerol metabolism plays in biofilm formation by P. aeruginosa. We report that glycerol metabolism promotes biofilm formation by both a chronic CF isolate (FRD1) and a wound isolate (PAO1) of P. aeruginosa. Moreover, loss of the GlpR regulator, which represses the expression of genes involved in glycerol metabolism, enhances biofilm formation in FRD1 through the upregulation of Pel polysaccharide. Taken together, our results suggest that glycerol metabolism may be a key factor that contributes to P. aeruginosa persistence by promoting biofilm formation. PMID- 27392248 TI - Consistent scaling of population structure across landscapes despite intraspecific variation in movement and connectivity. AB - Understanding the spatial scale of population structure is fundamental to long standing tenets of population biology, landscape ecology and conservation. Nonetheless, identifying such scales has been challenging because a key factor that influences scaling - movement among patches or local populations - is a multicausal process with substantial phenotypic and temporal variation. We resolve this problem via a novel application of network modularity. When applied to movements, modularity provides a formal description of the functional aggregation of populations and identifies potentially critical scales for ecological and evolutionary dynamics. We first test for modularity using several different types of biologically relevant movements across the entire geographic range of an endangered bird, the snail kite (Rostrhamus sociabilis plumbeus). We then ask whether variation in movement based on (i) age, (ii) sex and (iii) time (annual, seasonal and within-season movements) influences spatial population structure (i.e. modularity) in snail kites. We identified significant modularity in annual dispersal of snail kites (all adults, males only, females only, and juveniles only) and in within-breeding season movements of adults, yet no evidence of modularity in seasonal (non-breeding) movements. For those movements with observed modular structure, we found striking similarities in the spatial configuration of population structure, even though movement properties varied considerably among these different types of movements. Our results suggest that the emergence of modularity in population networks can be robust despite movement heterogeneity and differences in patch-based measures of connectivity. Furthermore, our comparison of the population structure and connectivity across multiple movement phases helps to identify wetland patches most critical to population connectivity at multiple spatiotemporal scales. We argue that understanding modularity in populations may provide a robust complement to existing measures of population structure and connectivity and will help to clarify the limiting roles of movement for populations. Such information is increasingly needed for interpreting population persistence and guiding effective conservation strategies with ongoing environmental change. PMID- 27392249 TI - Fractionation of Mercury Stable Isotopes during Microbial Methylmercury Production by Iron- and Sulfate-Reducing Bacteria. AB - The biological production of monomethylmercury (MeHg) in soils and sediments is an important factor controlling mercury (Hg) accumulation in aquatic and terrestrial food webs. In this study we examined the fractionation of Hg stable isotopes during Hg methylation in nongrowing cultures of the anaerobic bacteria Geobacter sulfurreducens PCA and Desulfovibrio desulfuricans ND132. Both organisms showed mass-dependent, but no mass-independent fractionation of Hg stable isotopes during Hg methylation. Despite differences in methylation rates, the two bacteria had similar Hg fractionation factors (alphar/p = 1.0009 and 1.0011, respectively). Unexpectedly, delta(202)Hg values of MeHg for both organisms were 0.40/00 higher than the value of initial inorganic Hg after about 35% of inorganic Hg had been methylated. These results indicate that a (202)Hg enriched pool of inorganic Hg was preferentially utilized as a substrate for methylation by these organisms, but that multiple intra- and/or extracellular pools supplied inorganic Hg for biological methylation. Understanding the controls of the Hg stable isotopic composition of microbially produced MeHg is important to identifying bioavailable Hg in natural systems and the interpretation of Hg stable isotopes in aquatic food webs. PMID- 27392250 TI - Correction: A Computational Framework for 3D Mechanical Modeling of Plant Morphogenesis with Cellular Resolution. AB - [This corrects the article DOI: 10.1371/journal.pcbi.1003950.]. PMID- 27392251 TI - The nature and treatment of phonological text agraphia. AB - Phonological alexia and agraphia are written language disorders characterised by disproportionate difficulty reading and spelling nonwords in comparison to real words. In phonological alexia, it has been shown that, despite relatively accurate reading of words in isolation, text-level reading deficits are often marked and persistent. Specifically, some individuals demonstrate difficulty reading functors and affixes in sentences, a profile referred to as phonological text alexia. In this paper, we demonstrate an analogous manifestation of the phonological impairment on text-level writing and suggest the term "phonological text agraphia". We examined four individuals with phonological alexia/agraphia who also showed disproportionate difficulty writing well-formed sentences in comparison to their grammatical competence in spoken utterances. Implementation of a phonological treatment protocol resulted in significantly improved sublexical phonology skills as well as improvements in grammatical accuracy of written narratives. These findings support the notion of a common phonological impairment underlying nonword reading/spelling deficits and sentence-level difficulties. PMID- 27392252 TI - A Typology of ICU Patients and Families from the Clinician Perspective: Toward Improving Communication. AB - This paper presents an exploratory case study of clinician-patient communications in a specific clinical environment. It describes how intensive care unit (ICU) clinicians' technical and social categorizations of patients and families shape the flow of communication in these acute care settings. Drawing on evidence from a year-long ethnographic study of four ICUs, we develop a typology of patients and families as viewed by the clinicians who care for them. Each type, or category, of patient is associated with differing communication strategies, with compliant patients and families engaged in greater depth. In an era that prioritizes patient engagement through communication for all patients, our findings suggest that ICU teams need to develop new strategies for engaging and communicating with not just compliant patients and families, but those who are difficult as well. We discuss innovative methods for developing such strategies. PMID- 27392253 TI - Main Group Metal-Actinide Magnetic Coupling and Structural Response Upon U(4+) Inclusion Into Bi, Tl/Bi, or Pb/Bi Cages. AB - The encapsulation of actinide ions in intermetalloid clusters has long been proposed but was never realized synthetically. We report the isolation and experimental, as well as quantum chemical, characterization of the uranium centered clusters [U@Bi12](3-), [U@Tl2Bi11](3-), [U@Pb7Bi7](3-), and [U@Pb4Bi9](3 ), upon reaction of (EE'Bi2)(2-) (E = Ga, Tl, E' = Bi; E = E' = Pb) and [U(C5Me4H)3] or [U(C5Me4H)3Cl] in 1,2-diaminoethane. For [U@Bi12](3-), magnetic susceptibility measurements rationalize an unprecedented antiferromagnetic coupling between a magnetic U(4+) site and a unique radical Bi12(7-) shell. PMID- 27392254 TI - Phase Formation and Oxidation Behavior at 500 degrees C in a Ni-Co-Al Thin-Film Materials Library. AB - The complete ternary system Ni-Co-Al was fabricated as a thin film materials library by combinatorial magnetron sputtering and was annealed subsequently in several steps in Ar and under atmospheric conditions at 500 degrees C. Ni-Co-Al is the base system for both Ni- and Co-based superalloys. Therefore, the phases occurring in this system and their oxidation behavior is of high interest. The Ni Co-Al materials library was investigated using high-throughput characterization methods such as optical measurements, resistance screening, automated EDX, automated XRD, and XPS. From the obtained data a thin film phase diagram for the Ni-Co-Al system in its state after annealing at 500 degrees C in air was established. Furthermore, a surface oxide composition map of the full Ni-Co-Al system for oxidation at 500 degrees C was concluded. As a result, it could be shown that at 500 degrees C an amount of 10 at. % Al is necessary for a Ni-Co-Al thin film to produce a protective Al-oxide scale. PMID- 27392255 TI - Experimental Basicities of Superbasic Phosphonium Ylides and Phosphazenes. AB - Experimental basicities of some of the strongest superbases ever measured (phosphonium ylides) are reported, and by employing these compounds, the experimental self-consistent basicity scale of superbases in THF, reaching a pKalpha (estimate of pKa) of 35 and spanning more than 30 pKa units, has been compiled. Basicities of 47 compounds (around half of which are newly synthesized) are included. The solution basicity of the well-known t-Bu-N?P4(dma)9 phosphazene superbase is now rigorously linked to the scale. The compiled scale is a useful tool for further basicity studies in THF as well as in other solvents, in particular, in acetonitrile. A good correlation between basicities in THF and acetonitrile spanning 25 orders of magnitude gives access to experimentally supported very high (pKa > 40) basicities in acetonitrile, which cannot be directly measured. Analysis of structure-basicity trends is presented. PMID- 27392256 TI - An Internet-Assisted Weight Loss Intervention for Older Overweight and Obese Rural Women: A Feasibility Study. AB - Older Appalachian women are an understudied population with few resources available to prevent obesity and chronic disease. This study explored the feasibility of a 12-week weight loss intervention using Internet technology for older rural Appalachian women. The sample (N = 24) included women 55 years or older recruited from two senior centers in the Appalachian region. The women were randomly assigned to either an Internet program called "Lose It" (Internet program for recording of daily calories and physical activity) or to a daily wellness program (health tips) delivered via e-mail. The mean age of participants was 69 +/- 8 years. Their mean body mass index (kg/m) at baseline was 34.2 +/- 8. A significant difference (P = .036) was observed between intervention and control group scores on the Social Pressure Subscale. Both groups improved their intake of fruits and vegetables and lost weight from baseline to week 12. Internet weight loss programs appear feasible for older rural women. Internet-delivered weight loss interventions that provide a way to record daily calories, physical activity, and weight may provide a technology platform leading to increased self efficacy for weight loss. PMID- 27392257 TI - Moving Toward a Virtual Knowledge Platform for Faith Community Nurses. AB - In preparation for the development of a virtual knowledge platform for faith community nurses, a review of literature explored the prevalence and context of electronic knowledge management initiatives. The review revealed that healthcare, business, and global virtual knowledge platforms have been developed to elicit certain behaviors in users. For those who develop virtual knowledge platforms, the results are improved efficiency, innovation, accessibility, and cost savings. The main component of virtual knowledge platforms is a central repository or an infrastructure where knowledge is created, acquired, stored (documents), updated, and shared internally and externally. The refinery processes refer to technology mechanisms that make content accessible. A transparent collaboration among information technology, knowledge owners, and users is needed to successfully sustain a virtual knowledge platform. Faith community nurses often practice in isolated environments. A virtual knowledge platform where practice resources and tools are shared, and communication among peers exists, may improve knowledge and skills and result in a positive impact on patient outcomes. PMID- 27392258 TI - Effectiveness of Web-Based Interventions for Managing Diabetes in Korea. AB - Web-based interventions are an emerging approach to managing diabetes in Korea. This review systematically evaluated the effectiveness of these interventions. To identify studies for review, a search of online electronic databases was conducted; the search was guided by the Cochrane processes and Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Ten studies published between 2005 and 2015 that met the inclusion criteria were assessed for methodological quality and analyzed. All 10 studies had participants that were Korean adults diagnosed with type 2 diabetes. The analysis revealed that the Web-based interventions under review, which included self-care management services and decision support systems, improved measures of biophysiological, psychobehavioral, and satisfaction of care outcomes. This review found strong evidence of the effectiveness of these Web-based interventions in improving glucose controls. Future studies with rigorous research design that study large populations with different age groups and have structured descriptions of interventions are recommended. Nurses and healthcare providers can use the evidence in this review to improve outcomes in diabetes management, and healthcare policy makers can use this review to evaluate whether to adopt these interventions as a care coordination strategy. PMID- 27392259 TI - Current status of glucose test prescription for hypertensive outpatients. AB - OBJECTIVES: The prescription of glucose test for essential hypertensive patients is estimated to be very low in cardiology clinics, but it has not been well studied. The aim of the present study aimed to investigate glucose test prescription for the hypertensive outpatients. METHODS: Five thousand two hundred and forty hypertensive outpatients without previous known diabetes were recruited consecutively by cardiologists from >90 hospitals. Blood glucose prescription records were collected by special investigators. RESULTS: Of the 5240 hypertensive outpatients recruited, only 258 (4.92%) were prescribed glucose tests, and 12.17% and 42.61% of them were diagnosed with diabetes mellitus and impaired glucose tolerance, respectively. Patients' hypertension stage, cardiovascular disease history, diabetes family history, dyslipidemia, and hospital level were associated with higher odds of glucose tests prescription. CONCLUSION: Glucose tests were poorly prescribed for hypertensive outpatients in China. It was highly recommended to raise cardiologists' awareness to prescribe glucose tests for hypertensive outpatients who were with high cardiovascular risk factors. PMID- 27392260 TI - Memory T cells specific for HBV enumerated by a peptide-based cultured enzyme linked immunospot assay in healthy HBV-vaccinated subjects. AB - Hepatitis B vaccine is the most effective strategy to control hepatitis B virus (HBV) infection and disease. It is considered that an anti-HBs (antibodies against HBV surface antigen) titer >10 mIU/ml, measured shortly after a complete vaccination schedule, provides protection against infection. Approximately 4-10% of healthy individuals fail to respond to 3-dose vaccination. Long-term HBV specific memory T-cell response has not been fully investigated, mainly due to the lack of a suitable assay. We quantified HBV-specific expandable memory T cells by using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay. Cultured ELISPOT response to an overlapping peptide pool representing the complete L (large) HBV envelope polypeptide was evaluated in 41 healthy subjects vaccinated 15-20 y earlier and 5 unvaccinated. Plasma samples were tested for anti-HBs. Vaccinated subjects had significantly higher HBV-specific T-cellular response than unvaccinated (p = 0.0002). HBV-specific T-cell response was mainly mediated by CD4+ T cells. No concordance was found between cultured ELISPOT and anti-HBs data in vaccinated subjects. Thirty-one (76%) vaccinated subjects were responders (anti-HBs >10 mIU/ml). Nineteen (46%) vaccinated subjects were considered to be responders in cultured ELISPOT. Twenty-two (54%) vaccinated subjects were considered non-responders in cultured ELISPOT; 5 of them (23%) were also humoral non-responders. About 12% of healthy HBV-vaccinated subjects are both humoral and cellular non-responders. Although the prognostic value of this assay has not been established in terms of predictability for susceptibility to de-novo HBV infection, ELISPOT data suggest that these subjects may be at risk for HBV infection and disease, especially health care workers. PMID- 27392262 TI - Effect of Kinesio Taping on Pain and Functional Disability in Chronic Nonspecific Low Back Pain: A Randomized Clinical Trial. AB - STUDY DESIGN: A randomized controlled trial with 2-week Kinesio taping intervention. OBJECTIVE: The aim of the study was to investigate the effectiveness of Kinesio taping application on pain, functional disability, and trunk flexion range of motion (ROM) in patients with chronic nonspecific low back pain (chronic NSLBP). SUMMARY OF BACKGROUND DATA: Kinesio taping is a therapeutic tool used for treatment of chronic NSLBP. However, there is little scientific evidence that describes its clinical efficacy. METHODS: Forty-four patients with chronic NSLBP were randomized into experimental group (n = 21) and placebo group (n = 23). The experimental group was treated with Erector Spinae Taping, whereas the placebo group was treated with placebo taping. The primary endpoint was pain intensity on visual analog scale. Secondary endpoints were functional disability on Arabic version of Oswestry disability index (ODI) and trunk flexion ROM on Modified Schober's test. All measurements were recorded at baseline (W0), after 2 week intervention (W2), and at 4-week (W4) follow-up. RESULTS: Both group were comparable at baseline (P > 0.05). The experimental group had a greater decrease in pain than the placebo group after W2 of intervention (mean between-group difference 2.05 cm, 95% confidence interval [CI] = 1.38-2.71 points). This was maintained to W4 follow-up (2.25 cm, 95% CI = 1.67-2.82 points). At W2, the experimental group had significantly greater improvement in disability, by 3.90 points (95% CI = 1.68-8.54 points). This effect was significant at W4 follow-up (5.6, 95% CI = 2.65-8.54 points). Similarly trunk flexion ROM was significantly better at W2 (-0.71 cm, 95% CI = -0.85 to -0.56) and W4 follow-up (-0.73 cm, 95% CI = -0.88 to -0.58). CONCLUSION: Kinesio taping reduces pain and disability and improves trunk flexion ROM after 2 weeks of application. However, thesis effects were very small to be considered clinically relevant and meaningful when compared with placebo taping. LEVEL OF EVIDENCE: 2. PMID- 27392263 TI - Elevated transaminase levels among overweight adolescents in eastern China. AB - AIM: We aim to investigate the prevalence and correlates of suspected nonalcoholic fatty liver disease (NAFLD) among adolescents in eastern China. METHODS: The study uses data from the annual health examination among all students finishing high school who applied for university entrance in Changzhou City between 2012 and 2014 (n = 19 162). Suspected NAFLD was defined as overweight plus elevated alanine aminotransferase levels (males >25.8 U/L; females >22.1 U/L). RESULTS: The prevalence of suspected NAFLD was 6.9% (11.1% in males and 2.6% in females). Students from medium and high socio-economic status (SES) schools had a higher prevalence of suspected NAFLD than those from low SES schools. Prehypertension had similar odds ratios (ORs, above four) for suspected NAFLD in both genders. The positive association between impaired fasting glucose/diabetes and suspected NAFLD was stronger in females than males. Compared with those born in autumn, these born in spring (OR 1.39; 95% CI, 1.16-1.67) and winter (OR 1.24; 95% CI, 1.04-1.49) had increased odds to have suspected NAFLD in males but not in females. CONCLUSION: Suspected NAFLD was prevalent among urban university applicants especially in males and those of high SES. Prehypertension was positively related to suspected NAFLD. Season of birth was related to suspected NAFLD in males but not in females. PMID- 27392261 TI - Early-Life Exposure to the Great Smog of 1952 and the Development of Asthma. AB - RATIONALE: Little is known about the long-term effects of air pollution exposure and the root causes of asthma. We use exposure to intense air pollution from the 1952 Great Smog of London as a natural experiment to examine both issues. OBJECTIVES: To determine whether exposure to extreme air pollution in utero or soon after birth affects asthma development later in life. METHODS: This was a natural experiment using the unanticipated pollution event by comparing the prevalence of asthma between those exposed to the Great Smog in utero or the first year of life with those conceived well before or after the incident and those residing outside the affected area at the time of the smog. MEASUREMENTS AND MAIN RESULTS: Prevalence of asthma during childhood (ages 0-15) and adulthood (ages >15) is analyzed for 2,916 respondents to the Life History portion of the English Longitudinal Study on Aging born from 1945 to 1955. Exposure to the Great Smog in the first year of life increases the likelihood of childhood asthma by 19.87 percentage points (95% confidence interval [CI], 3.37-36.38). We also find suggestive evidence that early-life exposure led to a 9.53 percentage point increase (95% CI, -4.85 to 23.91) in the likelihood of adult asthma and exposure in utero led to a 7.91 percentage point increase (95% CI, -2.39 to 18.20) in the likelihood of childhood asthma. CONCLUSIONS: These results are the first to link early-life pollution exposure to later development of asthma using a natural experiment, suggesting the legacy of the Great Smog is ongoing. PMID- 27392264 TI - Probabilistic versus deterministic tractography for delineation of the cortico subthalamic hyperdirect pathway in patients with Parkinson disease selected for deep brain stimulation. AB - OBJECTIVE Diffusion-weighted MRI (DWI) and tractography allows noninvasive mapping of the structural connections of the brain, and may provide important information for neurosurgical planning. The hyperdirect pathway, connecting the subthalamic nucleus (STN) with the motor cortex, is assumed to play a key role in mediating the effects of deep brain stimulation (DBS), which is an effective but poorly understood treatment for Parkinson disease. This study aimed to apply recent methodological advances in DWI acquisition and analysis to the delineation of the hyperdirect pathway in patients with Parkinson disease selected for surgery. METHODS High spatial and angular resolution DWI data were acquired preoperatively from 5 patients with Parkinson disease undergoing DBS. The authors compared the delineated hyperdirect pathways and associated STN target maps generated by 2 different tractography methods: a tensor-based deterministic method, typically available in clinical settings, and an advanced probabilistic method based on constrained spherical deconvolution. In addition, 10 high resolution data sets with the same scanning parameters were acquired from a healthy control participant to assess the robustness of the tractography results. RESULTS Both tractography approaches identified connections between the ipsilateral motor cortex and the STN. However, the 2 methods provided substantially different target regions in the STN, with the target center of gravity differing by > 1.4 mm on average. The probabilistic method (based on constrained spherical deconvolution) plausibly reconstructed a continuous set of connections from the motor cortex, terminating in the dorsolateral region of the STN. In contrast, the tensor-based method reconstructed a comparatively sparser and more variable subset of connections. Furthermore, across the control scans, the probabilistic method identified considerably more consistent targeting regions within the STN compared with the deterministic tensor-based method, which demonstrated a 1.9-2.4 times higher variation. CONCLUSIONS These data provide a strong impetus for the use of a robust probabilistic tractography framework based on constrained spherical deconvolution, or similar advanced DWI models, in clinical settings. The inherent limitations and demonstrated inaccuracy of the tensor-based method leave it questionable for use in high-precision stereotactic DBS surgery. The authors have also described a straightforward method for importing tractography-derived information into any clinical neuronavigation system, based on the generation of track-density images. PMID- 27392265 TI - Gamma Knife radiosurgery for glomus jugulare tumors: a single-center series of 75 cases. AB - OBJECTIVE Glomus jugulare tumors are rare indolent tumors that frequently involve the lower cranial nerves (CNs). Complete resection can be difficult and associated with lower CN injury. Gamma Knife radiosurgery (GKRS) has established its role as a noninvasive alternative treatment option for these often formidable lesions. The authors aimed to review their experience at the National Centre for Stereotactic Radiosurgery, Sheffield, United Kingdom, specifically the long-term tumor control rate and complications of GKRS for these lesions. METHODS Clinical and radiological data were retrospectively reviewed for patients treated between March 1994 and December 2010. Data were available for 75 patients harboring 76 tumors. The tumors in 3 patients were treated in 2 stages. Familial and/or hereditary history was noted in 12 patients, 2 of whom had catecholamine secreting and/or active tumors. Gamma Knife radiosurgery was the primary treatment modality in 47 patients (63%). The median age at the time of treatment was 55 years. The median tumor volume was 7 cm3, and the median radiosurgical dose to the tumor margin was 18 Gy (range 12-25 Gy). The median duration of radiological follow-up was 51.5 months (range 12-230 months), and the median clinical follow-up was 38.5 months (range 6-223 months). RESULTS The overall tumor control rate was 93.4% with low CN morbidity. Improvement of preexisting deficits was noted in 15 patients (20%). A stationary clinical course and no progression of symptoms were noted in 48 patients (64%). Twelve patients (16%) had new symptoms or progression of their preexisting symptoms. The Kaplan-Meier actuarial tumor control rate was 92.2% at 5 years and 86.3% at 10 years. CONCLUSIONS Gamma Knife radiosurgery offers a risk-versus-benefit treatment option with very low CN morbidity and stable long-term results. PMID- 27392266 TI - Implications of transitioning to a resident night float system in neurosurgery: mortality, length of stay, and resident experience. AB - OBJECTIVE Many neurosurgical training programs have moved from a 24-hour resident call system to a night float system, but the impact on outcomes is unclear. Here, the authors compare length of stay (LOS) for neurosurgical patients admitted before and after initiation of a night float system at a tertiary care training hospital. METHODS The neurosurgical residency at the University of Alabama at Birmingham transitioned from 24-hour call to a night float resident coverage system in July 2013. In this cohort study, all patients admitted to the neurosurgical service for 1 year before and 1 year after this transition were compared with respect to hospital and ICU LOSs, adjusted for potential confounders. RESULTS A total of 4619 patients were included. In the initial bivariate analysis, night float was associated with increased ICU LOS (p = 0.032) and no change in overall LOS (p = 0.65). However, coincident with the transition to a night float system was an increased frequency of resident service transitions, which were highly associated with hospital LOS (p < 0.01) and ICU LOS (p < 0.01). After adjusting for resident service transitions, initiation of the night float system was associated with decreased hospital LOS (p = 0.047) and no change in ICU LOS (p = 0.35). CONCLUSIONS This study suggests that a dedicated night float resident may improve night-to-night continuity of care and decrease hospital LOS, but caution must be exercised when initiation of night float results in increased resident service transitions. PMID- 27392267 TI - Bilateral chronic subdural hematoma: unilateral or bilateral drainage? AB - OBJECTIVE Bilateral chronic subdural hematoma (bCSDH) is a common neurosurgical condition frequently associated with the need for retreatment. The reason for the high rate of retreatment has not been thoroughly investigated. Thus, the authors focused on determining which independent predictors are associated with the retreatment of bCSDH with a focus on surgical laterality. METHODS In a national database of CSDHs (Danish Chronic Subdural Hematoma Study) the authors retrospectively identified all bCSDHs treated in the 4 Danish neurosurgical departments over the 3-year period from 2010 to 2012. Univariate and multivariate analyses were performed to determine the relationship between retreatment of bCSDH and clinical, radiological, and surgical variables. RESULTS Two hundred ninety-one patients with bCSDH were identified, and 264 of them underwent unilateral (136 patients) or bilateral (128 patients) surgery. The overall retreatment rate was 21.6% (57 of 264 patients). Cases treated with unilateral surgery had twice the risk of retreatment compared with cases undergoing bilateral surgery (28.7% vs 14.1%, respectively, p = 0.002). In accordance with previous studies, the data also showed that a separated hematoma density and the absence of postoperative drainage were independent predictors of retreatment. CONCLUSIONS In bCSDHs bilateral surgical intervention significantly lowers the risk of retreatment compared with unilateral intervention and should be considered when choosing a surgical procedure. PMID- 27392268 TI - Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats. AB - OBJECTIVE There is increasing interest in neuromodulation for addiction. Methamphetamine abuse is a global health epidemic with no proven treatment. The objective of this study was to examine the effects of intermittent nucleus accumbens shell (AcbSh) deep brain stimulation (DBS) on operant methamphetamine intake and on methamphetamine seeking when stimulation is delivered in an environment different from that of drug use. METHODS Eighteen rats were implanted with intravenous (IV) catheters and bilateral AcbSh electrodes and subsequently underwent daily sessions in 2-lever (active/methamphetamine and inactive/no reward) operant chambers to establish IV methamphetamine self-administration. After stable responding was achieved, 3 hours of DBS or sham treatment was administered (sham: 0 uA, n = 8; active: 200 uA, n = 10) in a separate nondrug environment prior to the daily operant sessions for 5 consecutive days. Immediately following each DBS/sham treatment, rats were placed in the operant chambers to examine the effects of remote stimulation on methamphetamine intake. After the 5 days of therapy were finished, rats reestablished a posttreatment baseline, followed by extinction training, abstinence, and 1 day of relapse testing to assess methamphetamine-seeking behavior. RESULTS There was a decrease in total methamphetamine intake in rats receiving active DBS versus sham on Days 1 (42%) and 2 (44%). Methamphetamine administration returned to baseline levels following the cessation of DBS therapy. Compared with baseline drug responding, methamphetamine seeking was reduced (57%) in the DBS group but not in the sham group. CONCLUSIONS It is feasible to deliver noncontinuous DBS outside of the drug use environment with a resultant decrease in IV methamphetamine intake and seeking. The AcbSh is a neuroanatomical substrate for psychostimulant reinforcement and may be a target for intermittent neuromodulatory therapies that could be administered during brief periods of sobriety. PMID- 27392269 TI - Episodic hemilaryngopharyngeal spasm (HELPS) syndrome: case report of a surgically treatable novel neuropathy. AB - The authors describe a novel cranial neuropathy manifesting with life-threatening episodic hemilaryngopharyngeal spasm (HELPS). A 50-year-old woman presented with a 4-year history of intermittent throat contractions, escalating to life threatening respiratory distress. Botulinum toxin injections into her right vocal cord reduced the severity of her spasms, but the episodes continued to occur. MRI demonstrated a possible neurovascular conflict involving the cranial nerve IX-X complex and the posterior inferior cerebellar artery. Microvascular decompression of the upper rootlets of the vagal nerve eliminated her HELPS without complication. The authors propose a mechanism of HELPS implicating isolated involvement of the upper motor rootlets of the vagus nerve. PMID- 27392270 TI - Imaging of spontaneous intraventricular rupture of a septum pellucidum colloid cyst: case report. AB - Intraventricular rupture of a colloid cyst is a rare phenomenon and has been proposed as a mechanism for sudden death in patients with colloid cysts. Imaging of a colloid cyst during rupture has been described in only one other instance. The authors report a highly unusual case of a 53-year-old man who presented with acute onset headaches and imaging findings of hydrocephalus caused by a colloid cyst originating from the septum pellucidum and superior surface of the roof of the third ventricle. Interestingly, the colloid cyst revealed imaging signs of intraventricular rupture characterized by a tail-like drainage of cystic contents into the occipital horn of the lateral ventricle. The patient was surgically treated with a craniotomy and transcallosal approach to the colloid cyst, where it was noted that the cyst wall was spontaneously open. This rare case highlights unique imaging findings of a rare event in an infrequent pathology confirmed with intraoperative microscopy. The authors further document the process of cyst rupture and speculate on its pathomechanisms. PMID- 27392271 TI - Case series of ventriculopleural shunts in adults: a single-center experience. AB - OBJECTIVE The peritoneal cavity is widely used as the destination of choice for cerebrospinal fluid shunts. Various alternative sites have been used, particularly in the presence of certain contraindications. The pleural cavity has been used; however, a paucity of evidence details ventriculopleural (VPL) shunt survival, complication, and revision rates in adults. The aim of this study was to present a single center's experience with VPL shunts, identifying complication, revision, and survival rates. METHODS A single-center, retrospective case series analysis was conducted for VPL shunt insertions and revisions over a period of 5 years. Demographic as well as clinical data were collected. Ventriculopleural shunt survival was assessed using Kaplan-Meier curves and the log rank (Cox-Mantel) test. RESULTS Twenty-two VPL shunts were inserted in 19 patients. Median survival of the VPL shunts was 14 months. Pathological indication for the VPL shunt did not significantly affect survival. A total of 10 complications was observed: 2 infections, 2 cases of overdrainage, 2 obstructions, 1 distal catheter retraction, 2 symptomatic pleural effusions, and 1 asymptomatic pleural effusion. CONCLUSIONS Ventriculopleural shunting is a safe and viable second-line procedure for cases in which ventriculoperitoneal shunts are unsuitable. While VPL shunts have a high revision rate, their complication rate is comparable to that of VP shunts. Ventriculopleural shunt survival can be improved by careful patient selection and the implementation of a combination of valves with antisiphon devices. PMID- 27392272 TI - Letter to the Editor: Diagnosis and prediction of surgical outcome in normal pressure hydrocephalus. PMID- 27392274 TI - Collision-induced dissociation of uranyl-methoxide and uranyl-ethoxide cations: Formation of UO2 H(+) and uranyl-alkyl product ions. AB - RATIONALE: The lower levels of adventitious H2 O in a linear ion trap allow the fragmentation reactions of [UO2 OCH3 ](+) and [UO2 OCH2 CH3 ](+) to be examined in detail. METHODS: Methanol- and ethanol-coordinated UO2 (2+) -alkoxide precursors were generated by electrospray ionization (ESI). Multiple-stage tandem mass spectrometry (MS(n) ) and collision-induced dissociation (CID) were performed using a linear ion trap mass spectrometer. RESULTS: CID of [UO2 OCH3 (CH3 OH)n ](+) and [UO2 OCH2 CH3 (CH3 CH2 OH)n ](+) , n = 3 and 2, causes loss of neutral alcohol ligands, leading ultimately to bare uranyl-alkoxide species. Comparison of 'native' to deuterium-labeled precursors reveals dissociation pathways not previously observed in 3-D ion trap experiments. CONCLUSIONS: UO2 H(+) is generated from [UO2 OCH3 ](+) by transfer of H from the methyl group. Variable-energy and variable-time CID experiments suggest that the apparent threshold for production of UO2 H(+) is lower than for UO2 (+) , but the pathway is kinetically less favored for the former than for the latter. CID experiments reveal that [UO2 OCH2 CH3 ](+) dissociates to generate [UO2 CH3 ](+) , a relatively rare species with a U-C bond, and [UO2 (O = CH2 )](+) . PMID- 27392273 TI - Permeability Coefficients of Lipophilic Compounds Estimated by Computer Simulations. AB - The ability of a drug to cross the intestine-blood barrier is a key quantity for drug design and employment and is normally quantified by the permeability coefficient P, often evaluated in the so-called Caco-2 assay. This assay is based on measuring the initial growth rate of the concentration of the drug beyond the cellular barrier but not its steady-state flux through the membrane. This might lead to confusion since, in the case of lipophilic drugs, the initial slope is strongly affected by the retention of the drug in the membrane. This effect is well known but seldom considered in the assay. Here, we exploit all-atoms molecular dynamics and bias exchange metadynamics to calculate the concentration of two lipophilic drugs across a model membrane as a function of time. This allows estimating both the steady-state flux and the initial slope of the concentration growth and comparing Caco-2 and steady-state estimates of P. We show that our computational procedure is able to reproduce the experimental values, although these may differ from the permeability coefficients by orders of magnitude. Our findings are generalized by a simplified one-dimensional model of the permeation process that may act as a roadmap to assess which measure of membrane permeability would be more appropriate and, consequently, whether retention corrections should be included in estimates based on Caco-2 assays. PMID- 27392275 TI - Two-photon absorption in gapped bilayer graphene with a tunable chemical potential. AB - Despite the now vast body of two-dimensional materials under study, bilayer graphene remains unique in two ways: it hosts a simultaneously tunable band gap and electron density; and stems from simple fabrication methods. These two advantages underscore why bilayer graphene is critical as a material for optoelectronic applications. In the work that follows, we calculate the one- and two-photon absorption coefficients for degenerate interband absorption in a graphene bilayer hosting an asymmetry gap and adjustable chemical potential-all at finite temperature. Our analysis is comprehensive, characterizing one- and two photon absorptive behavior over wide ranges of photon energy, gap, chemical potential, and thermal broadening. The two-photon absorption coefficient for bilayer graphene displays a rich structure as a function of photon energy and band gap due to the existence of multiple absorption pathways and the nontrivial dispersion of the low energy bands. This systematic work will prove integral to the design of bilayer-graphene-based nonlinear optical devices. PMID- 27392276 TI - Dramatic Changes in the Solubilities of Ions Induced by Ligand Addition in Biphasic System D2O/DNO3//[C1C4im][Tf2N]: A Phenomenological Study. AB - The solubilities of C1C4im(+) and Tf2N(-) in nitric aqueous phases have been measured for several ligand types and concentrations (0.04 M tributylphosphine oxide, 0.05 M N,N'-dimethyl-N,N'-dibutylmalonamide, 0.10 M 1-methyl-3-[4 (dibutylphosphinoyl)butyl]-3H-imidazol-1-ium bis(trifluoromethylsulphonyl)imidate, and 1.1 M N,N-dihexyloctanamide). The data evidence a significant difference between the solubilities of the cations and anions of the ionic liquid as a consequence of several ion-exchange and/or ion pairing mechanisms involving all ions present in the system as well as the protonation/nitric-extraction ability of the ligand. PMID- 27392277 TI - Cerebral sinovenous thrombosis in children and young adults with acute lymphoblastic leukaemia - a cohort study from the United Kingdom. PMID- 27392278 TI - Theoretical Principles to Guide the Teaching of Adjectives to Children Who Struggle With Word Learning: Synthesis of Experimental and Naturalistic Research With Principles of Learning Theory. AB - PURPOSE: The purpose of this tutorial is to provide clinicians with a theoretically motivated and evidence-based approach to teaching adjectives to children who struggle with word learning. METHOD: Given that there are almost no treatment studies to guide this topic, we have synthesized findings from experimental and theoretical literature to come up with a principles-based approach to treatment. RESULTS: We provide a sample lesson plan, incorporating our 3 theoretical principles, and describe the materials chosen and methods used during treatment and assessment. CONCLUSION: This approach is theoretically motivated, but it needs to be empirically tested. PMID- 27392279 TI - Effects of leaf water evaporative 2 H-enrichment and biosynthetic fractionation on leaf wax n-alkane delta2 H values in C3 and C4 grasses. AB - Leaf wax n-alkane delta2 H values carry important information about environmental and ecophysiological processes in plants. However, the physiological and biochemical drivers that shape leaf wax n-alkane delta2 H values are not completely understood. It is particularly unclear why n-alkanes in grasses are typically 2 H-depleted compared with plants from other taxonomic groups such as dicotyledonous plants and why C3 grasses are 2 H-depleted compared with C4 grasses. To resolve these uncertainties, we quantified the effects of leaf water evaporative 2 H-enrichment and biosynthetic hydrogen isotope fractionation on n alkane delta2 H values for a range of C3 and C4 grasses grown in climate controlled chambers. We found that only a fraction of leaf water evaporative 2 H enrichment is imprinted on the leaf wax n-alkane delta2 H values in grasses. This is interesting, as previous studies have shown in dicotyledonous plants a nearly complete transfer of this 2 H-enrichment to the n-alkane delta2 H values. We thus infer that the typically observed 2 H-depletion of n-alkanes in grasses (as opposed to dicots) is because only a fraction of the leaf water evaporative 2 H enrichment is imprinted on the delta2 H values. Our experiments also show that differences in n-alkane delta2 H values between C3 and C4 grasses are largely the result of systematic differences in biosynthetic fractionation between these two plant groups, which was on average -1980/00 and-1590/00 for C3 and C4 grasses, respectively. PMID- 27392280 TI - Examining How Communication and Knowledge Relate to Singaporean Youths' Perceived Risk of Haze and Intentions to Take Preventive Behaviors. AB - As Southeast Asia has experienced haze crises in recent years, encouraging Singaporeans to take preventive measures against negative health outcomes during haze is a growing concern. This study examines how communication factors (i.e., attention to traditional media and new media, interpersonal discussion, and knowledge) can inform Singaporeans about haze and influence their risk perceptions and intentions to undertake self-protective measures. The web survey of 410 respondents shows that attention to traditional media, attention to new media, interpersonal discussion, knowledge, and risk perception are positively associated with intention to take preventive measures. However, only interpersonal discussion is related to risk perception. Theoretical as well as practical implications of the findings are discussed. PMID- 27392281 TI - The ontogeny of tolerance curves: habitat quality vs. acclimation in a stressful environment. AB - Stressful environments affect life-history components of fitness through (i) instantaneous detrimental effects, (ii) historical (carry-over) effects and (iii) history-by-environment interactions, including acclimation effects. The relative contributions of these different responses to environmental stress are likely to change along life, but such ontogenic perspective is often overlooked in studies of tolerance curves, precluding a better understanding of the causes of costs of acclimation, and more generally of fitness in temporally fine-grained environments. We performed an experiment in the brine shrimp Artemia to disentangle these different contributions to environmental tolerance, and investigate how they unfold along life. We placed individuals from three clones of A. parthenogenetica over a range of salinities during a week, before transferring them to a (possibly) different salinity for the rest of their lives. We monitored individual survival at repeated intervals throughout life, instead of measuring survival or performance at a given point in time, as commonly done in acclimation experiments. We then designed a modified survival analysis model to estimate phase-specific hazard rates, accounting for the fact that individuals may share the same treatment for only part of their lives. Our approach allowed us to distinguish effects of salinity on (i) instantaneous mortality in each phase (habitat quality effects), (ii) mortality later in life (history effects) and (iii) their interaction. We showed clear effects of early salinity on late survival and interactions between effects of past and current environments on survival. Importantly, analysis of the ontogenetic dynamics of the tolerance curve reveals that acclimation affects different parts of the curve at different ages. Adopting a dynamical view of the ontogeny of tolerance curve should prove useful for understanding niche limits in temporally changing environments, where the full sequence of environments experienced by an individual determines its overall environmental tolerance, and how it changes throughout life. PMID- 27392282 TI - High prevalence of blaVIM-1 gene in bacteria from Brazilian soil. AB - This study investigated bacteria from soil samples to (i) determine the main bacterial genera and species having resistance to carbapenem and other beta lactams and (ii) establish if the mechanism of resistance was due to the production of metallo-beta-lactamases. The isolates were characterized by PCR for metallo-beta-lactamases and integrons, by antimicrobial susceptibility testing, and by sequencing. The antimicrobial profile of 40 imipenem-resistant Gram positive soil isolates from all Brazilian regions demonstrated that 31 (77.5%) of them were multidrug resistant. Among the 40 isolates, 19 presented the blaVIM gene and class 1 integrons by PCR. Six of the 19 isolates were identified as Paenibacillus sp., 12 as Bacillus sp., and just 1 was classified as Staphylococcus sp., by sequencing of the 16S rRNA gene. These results suggest that bacteria from soil can act as a source of blaVIM-1 genes, representing a threat to public health. PMID- 27392283 TI - Percentile Values for the Anthropometric Dimensions of Triplet Neonates - Analysis of German Perinatal Survey Data of 2007-2011 from all States of Germany. PMID- 27392284 TI - [The Professional Practice of Midwives in Home-based Postnatal Care: A Literature Analysis]. AB - Due to the reduction of the length of stay in hospital, postnatal care today takes place primarily in the ambulant sector. Midwives provide the health care and support young families. This literature study examines home-based postnatal care from the perspectives of midwives with the aim of exploring how midwives provide postnatal care and what influencing factors exist. A systematic literature search was conducted. Studies that integrated the perceptions of midwives during their work in home-based postpartum care were included. A thematic analysis of the selected articles was undertaken. Besides monitoring the health and well-being of mother and child, the focus of postnatal care is on psychosocial aspects and on support and advice on issues concerning the new situation and structural changes in the family. However, midwives do not always feel sufficiently prepared for dealing with complex psychosocial issues and require extra knowledge and better access to information. Besides temporal limitations of midwives, continuity of care as well as different care approaches are also relevant. Home-based postnatal care constitutes complex professional procedures during an important period of life of women and their families. Besides ensuring continuity of care, appropriate knowledge resources and midwifery skills are required. The development of theory-guided concepts, improved training and further training programmes as well as a clearly defined provider contract can support the professional behaviour patterns of midwives. PMID- 27392285 TI - Choices of incidental findings of individuals undergoing genome wide sequencing, a single center's experience. AB - Genome wide sequencing is an emerging clinical tool that may provide information on genetic variants that are not directly related to the patient's primary disorder. These incidental findings (IFs) may include information about conditions that can be treated and may also indicate conditions for which treatments are not currently available. Data is currently limited regarding what IFs an individual would want to disclose. This study reports on 305 individual choices for return of IFs that were completed at the Medical College of Wisconsin's clinical sequencing laboratory. Individuals were given access to five categories of IFs to select from: no incidental findings, untreatable childhood disorders, treatable adulthood disorders, untreatable adulthood disorders, and carrier of a disorder. Retrospective chart review was conducted and individual choices were recorded and analyzed. The majority of individuals (76.1%) selected every IF to be reported, 14.4% wanted a subset of the options, and 9.5% did not want any IFs reported. This study contributes to the limited data that demonstrates what an individual would actually choose when undergoing genetic sequencing. Furthermore, this data supports the opinion that individuals want and utilize the ability to choose the findings reported. PMID- 27392286 TI - Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice. AB - OBJECTIVE: Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice. METHODS: The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level. RESULTS: The time of first seizure onset in group 1 was 109.7+/-4.3min, group 2 was 46.50+/-3.9min and group 3 was 165.4+/-13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2. CONCLUSION: Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels. PMID- 27392287 TI - Immobilization of the Gas Signaling Molecule H2 S by Radioisotopes: Detection, Quantification, and In Vivo Imaging. AB - Hydrogen sulfide (H2 S) has multifunctional roles as a gas signaling molecule in living systems. However, the efficient detection and imaging of H2 S in live animals is very challenging. Herein, we report the first radioisotope-based immobilization technique for the detection, quantification, and in vivo imaging of endogenous H2 S. Macrocyclic (64) Cu complexes that instantly reacted with gaseous H2 S to form insoluble (64) CuS in a highly sensitive and selective manner were prepared. The H2 S concentration in biological samples was measured by a thin-layer radiochromatography method. When (64) Cu-cyclen was injected into mice, an elevated H2 S concentration in the inflamed paw was clearly visualized and quantified by Cerenkov luminescence and positron emission tomography (PET) imaging. PET imaging was also able to pinpoint increased H2 S levels in a millimeter-sized infarcted lesion of the rat heart. PMID- 27392288 TI - The Strong Influence of Structure Polymorphism on the Conductivity of Peptide Fibrils. AB - Peptide fibril nanostructures have been advocated as components of future biotechnology and nanotechnology devices. However, the ability to exploit the fibril functionality for applications, such as catalysis or electron transfer, depends on the formation of well-defined architectures. Fibrils made of peptides substituted with aromatic groups are described presenting efficient electron delocalization. Peptide self-assembly under various conditions produced polymorphic fibril products presenting distinctly different conductivities. This process is driven by a collective set of hydrogen bonding, electrostatic, and pi stacking interactions, and as a result it can be directed towards formation of a distinct polymorph by using the medium to enhance specific interactions rather than the others. This method facilitates the detailed characterization of different polymorphs, and allows specific conditions to be established that lead to the polymorph with the highest conductivity. PMID- 27392289 TI - Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel. AB - Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD. PMID- 27392290 TI - Functional long circulating single walled carbon nanotubes for fluorescent/photoacoustic imaging-guided enhanced phototherapy. AB - Nanotherapeutics have been investigated for years, but only modest survival benefits were observed clinic. This is partially attributed to the short and rapid elimination of nanodrug after intravenous administration. In this study, a long circulation single wall carbon nanotube (SWCNT) complex was successfully fabricated through a new SWCNT dispersion agent, evans blue (EB). The complex was endowed with fluorescent imaging and photodynamic therapy ability by self assembly loading an albumin coupled fluorescent photosensitizer, Chlorin e6 (Ce6) via the high affinity between EB and albumin. The yielding multifunctional albumin/Ce6 loaded EB/carbon nanotube-based delivery system, named ACEC, is capable of providing fluorescent and photoacoustic imaging of tumors for optimizing therapeutic time window. Synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) were carried out as guided by imaging results at 24 h post-injection and achieved an efficient tumor ablation effect. Compared to PDT or PTT alone, the combined phototherapy managed to damage tumor and diminish tumor without recurrence. Overall, our study presents a SWCNT based theranostic system with great promising in dual modalities imaging guided PTT/PDT combined treatment of tumor. The applications of EB on SWCNT functionalization can be easily extended to the other nanomaterials for improving their in vivo stability and circulation time. PMID- 27392291 TI - In vitro screening of nanomedicines through the blood brain barrier: A critical review. AB - The blood-brain barrier accounts for the high attrition rate of the treatments of most brain disorders, which therefore remain one of the greatest health-care challenges of the twenty first century. Against this background of hindrance to brain delivery, nanomedicine takes advantage of the assembly at the nanoscale of available biomaterials to provide a delivery platform with potential to raising brain levels of either imaging or therapeutic agents. Nevertheless, to prevent later failure due to ineffective drug levels at the target site, researchers have been endeavoring to develop a battery of in vitro screening procedures that can predict earlier in the drug discovery process the ability of these cutting-edge drug delivery platforms to cross the blood-brain barrier for biomedical purposes. This review provides an in-depth analysis of the currently available in vitro blood-brain barrier models (both cell-based and non-cell-based) with the focus on their suitability for understanding the biological brain distribution of forthcoming nanomedicines. The relationship between experimental factors and underlying physiological assumptions that would ultimately lead to a more predictive capacity of their in vivo performance, and those methods already assayed for the evaluation of the brain distribution of nanomedicines are comprehensively discussed. PMID- 27392292 TI - Caution to use CO2 cryotherapy for foreign body removal in children: Authors' reply. PMID- 27392293 TI - A spontaneous mutation in MutL-Homolog 3 (HvMLH3) affects synapsis and crossover resolution in the barley desynaptic mutant des10. AB - Although meiosis is evolutionarily conserved, many of the underlying mechanisms show species-specific differences. These are poorly understood in large genome plant species such as barley (Hordeum vulgare) where meiotic recombination is very heavily skewed to the ends of chromosomes. The characterization of mutant lines can help elucidate how recombination is controlled. We used a combination of genetic segregation analysis, cytogenetics, immunocytology and 3D imaging to genetically map and characterize the barley meiotic mutant DESYNAPTIC 10 (des10). We identified a spontaneous exonic deletion in the orthologue of MutL-Homolog 3 (HvMlh3) as the causal lesion. Compared with wild-type, des10 mutants exhibit reduced recombination and fewer chiasmata, resulting in the loss of obligate crossovers and leading to chromosome mis-segregation. Using 3D structured illumination microscopy (3D-SIM), we observed that normal synapsis progression was also disrupted in des10, a phenotype that was not evident with standard confocal microscopy and that has not been reported with Mlh3 knockout mutants in Arabidopsis. Our data provide new insights on the interplay between synapsis and recombination in barley and highlight the need for detailed studies of meiosis in nonmodel species. This study also confirms the importance of early stages of prophase I for the control of recombination in large genome cereals. PMID- 27392294 TI - Maintenance of the adult Drosophila intestine: all roads lead to homeostasis. AB - Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues. PMID- 27392296 TI - Awareness of intramuscular capillary type hemangioma in the differential diagnosis of soft-tissue tumors in children. PMID- 27392295 TI - Schistosomiasis as a disease of stem cells. AB - Schistosomiasis is a devastating parasitic disease caused by flatworms of the genus Schistosoma. The complex life cycles and developmental plasticity of these parasites have captured the attention of parsitologists for decades, yet little is known on the molecular level about the developmental underpinnings that have allowed these worms to thrive as obligate parasites. Here, we describe basic schistosome biology and highlight how understanding the functions of stem cells in these worms will transform our understanding of these parasites. Indeed, we propose that schistosomiasis is fundamentally as disease of stem cells. We hope this review will attract new interest in the basic developmental biology of these important organisms. PMID- 27392297 TI - Carbon cycle responses of semi-arid ecosystems to positive asymmetry in rainfall. AB - Recent evidence shows that warm semi-arid ecosystems are playing a disproportionate role in the interannual variability and greening trend of the global carbon cycle given their mean lower productivity when compared with other biomes (Ahlstrom et al. 2015 Science, 348, 895). Using multiple observations (land-atmosphere fluxes, biomass, streamflow and remotely sensed vegetation cover) and two state-of-the-art biospheric models, we show that climate variability and extremes lead to positive or negative responses in the biosphere, depending on vegetation type. We find Australia to be a global hot spot for variability, with semi-arid ecosystems in that country exhibiting increased carbon uptake due to both asymmetry in the interannual distribution of rainfall (extrinsic forcing), and asymmetry in the response of gross primary production (GPP) to rainfall change (intrinsic response). The latter is attributable to the pulse-response behaviour of the drought-adapted biota of these systems, a response that is estimated to be as much as half of that from the CO2 fertilization effect during 1990-2013. Mesic ecosystems, lacking drought-adapted species, did not show an intrinsic asymmetric response. Our findings suggest that a future more variable climate will induce large but contrasting ecosystem responses, differing among biomes globally, independent of changes in mean precipitation alone. The most significant changes are occurring in the extensive arid and semi-arid regions, and we suggest that the reported increased carbon uptake in response to asymmetric responses might be contributing to the observed greening trends there. PMID- 27392298 TI - ABodyBuilder: Automated antibody structure prediction with data-driven accuracy estimation. AB - Computational modeling of antibody structures plays a critical role in therapeutic antibody design. Several antibody modeling pipelines exist, but no freely available methods currently model nanobodies, provide estimates of expected model accuracy, or highlight potential issues with the antibody's experimental development. Here, we describe our automated antibody modeling pipeline, ABodyBuilder, designed to overcome these issues. The algorithm itself follows the standard 4 steps of template selection, orientation prediction, complementarity-determining region (CDR) loop modeling, and side chain prediction. ABodyBuilder then annotates the 'confidence' of the model as a probability that a component of the antibody (e.g., CDRL3 loop) will be modeled within a root-mean square deviation threshold. It also flags structural motifs on the model that are known to cause issues during in vitro development. ABodyBuilder was tested on 4 separate datasets, including the 11 antibodies from the Antibody Modeling Assessment-II competition. ABodyBuilder builds models that are of similar quality to other methodologies, with sub-Angstrom predictions for the 'canonical' CDR loops. Its ability to model nanobodies, and rapidly generate models (~30 seconds per model) widens its potential usage. ABodyBuilder can also help users in decision-making for the development of novel antibodies because it provides model confidence and potential sequence liabilities. ABodyBuilder is freely available at http://opig.stats.ox.ac.uk/webapps/abodybuilder . PMID- 27392299 TI - Malunion of medial condyle fracture of the humerus: a case report. AB - Medial condyle fracture of the humerus is extremely rare in pediatric elbow fractures. We report a rare case of malunion of medial condyle fracture in a 10 year-old boy who had an injury on the right elbow at age 4. He was referred to our clinic because of severe varus deformity (the carrying angle was 191 degrees , unaffected side 172 degrees ) with instability. Extra-articular closing wedge osteotomy was performed. Five years after surgery, the carrying angle was 172 degrees and the patient had no pain and no difficulties with activities of daily living. PMID- 27392300 TI - The effectiveness of posterior knee capsulotomies and knee extension osteotomies in crouched gait in children with cerebral palsy. AB - Crouched gait is common in children with cerebral palsy (CP), and there are various treatment options. This study evaluated the effectiveness of single-event multilevel surgery including posterior knee capsulotomy or distal femoral extension osteotomy to correct knee flexion contracture in children with CP. Gait analyses were carried out to evaluate gait preoperatively and postoperatively. Significant improvements were found in physical examination and kinematic measures, which showed that children with CP and crouched gait who develop knee flexion contractures can be treated effectively using single-event multilevel surgery including a posterior knee capsulotomy or distal femoral extension osteotomy. PMID- 27392301 TI - Short-term results of early (before 6 months) open reduction of dislocated hips in arthrogryposis multiplex congenita. AB - The aim of this study was to report the results of early open reduction of hip dislocations in infants with arthrogryposis multiplex congenita. Seven patients who were under 6 months of age at the time of hip reduction, with a mean follow up period of 47.5+/-11.3 months after surgery, were included in this study. Four of seven patients (six of 13 hips) required additional hip surgeries during their follow-up. The short-term results of early open reduction of hips were not promising as most of the patients required additional hip surgeries. PMID- 27392303 TI - Tubercular dactylitis in children. AB - Tubercular dactylitis is a rare manifestation of skeletal tuberculosis in the paediatric population. Its clinical diagnosis is often delayed as local symptoms may easily be missed in children and constitutional features such as loss of weight, loss of appetite, night sweats, evening rise of temperature and history of close contact with a patient of tuberculosis may not always be present. Parents seek treatment only when they notice significant swelling or tenderness of fingers or hand in their children. Radiology and fine-needle aspiration cytology may help in establishing an early diagnosis. Astute multidrug antitubercular therapy is curative. PMID- 27392304 TI - Reduction and circumferential fusion for low-grade slips and intermediate-grade slips in pediatric spondylolisthesis. AB - Uninstrumented in-situ fusion of pediatric spondylolisthesis harbors a significant risk of suboptimal outcome. We suggest that reduction and instrumented fusion with deliberate protective measures against neurologic insult should be considered for the treatment of low-grade slips to intermediate-grade slips. This retrospective review of the clinical and radiographic data of 13 consecutively treated pediatric patients describes our experience with this approach. Eleven patients were pain free at the most recent follow-up and showed an average sustained correction in percent slip of 39%. This technique provides a safe alternative to in-situ fusion with the potential for improved outcomes. PMID- 27392305 TI - Partial double-layered patella in a nondysplasic adolescent. AB - Double-layered patella (DLP) is a rare patella-formation abnormality reported in association with multiple epiphyseal dysplasia. DLP is one of the five types of bipartite patella, caused by a coronal septum that divides the patella into anterior and posterior segments. Although the double layer of bone has been reported as complete, it may also manifest as partial, as in our case. A 13-year old male patient attended A&E after accidentally falling and sustaining a direct injury to his left knee, with pain in the anterior surface of the right patella. He was diagnosed with an incomplete vertical fracture of the left patella. An axial view radiography indicated an external partial DLP. No bone dysplasia was found. Computed tomographic scan and MRI showed partial DLP and bone marrow oedema because of the injury in the femoral condyle, but no fracture. The reason for highlighting this type of patella abnormality is to present the case of a patient without bone dysplasia, either partial or incomplete, that has not been reported previously. We also wish to emphasize the importance of not confusing it with a fracture in standard radiographies. PMID- 27392306 TI - Validating the Use of D for Measuring Lexical Diversity in Low-Income Kindergarten Children. AB - PURPOSE: Children from low-socioeconomic status families often perform poorly on standardized vocabulary assessments. The primary purpose of the study was to determine whether lexical diversity as measured by D (Malvern, Richards, Chipere, & Duran, 2004) serves as a valid measure of vocabulary in at-risk, low-income, predominantly African American kindergartners. METHOD: Kane's (1992) argument based approach was used to validate D. Six assumptions were examined. Kindergartners (N = 210) from a high-poverty, low-achievement region of the United States were recorded narrating a wordless picture book and assessed using the Expressive Vocabulary Test, Second Edition (Williams, 2007), and the Kaufman Test of Educational Achievement, Second Edition-Listening Comprehension subtest (Kaufman & Kaufman, 2004). RESULTS: D was distributed normally and did not vary as a function of language sample length or child ethnicity. D was significantly but weakly related to the Expressive Vocabulary Test, Second Edition, indicating some distinction between D and the Expressive Vocabulary Test, Second Edition, scores. Further, D was only marginally related to the Kaufman Test of Educational Achievement, Second Edition-Listening Comprehension subtest. CONCLUSIONS: Although evidence was somewhat mixed, the study supported the view that D is a potentially valid measure of lexical diversity among low-income, predominantly African American kindergartners and could be a useful supplement to standardized vocabulary measures. PMID- 27392307 TI - Stomatal acclimation to vapour pressure deficit doubles transpiration of small tree seedlings with warming. AB - Future climate change is expected to increase temperature (T) and atmospheric vapour pressure deficit (VPD) in many regions, but the effect of persistent warming on plant stomatal behaviour is highly uncertain. We investigated the effect of experimental warming of 1.9-5.1 degrees C and increased VPD of 0.5-1.3 kPa on transpiration and stomatal conductance (gs ) of tree seedlings in the temperate forest understory (Duke Forest, North Carolina, USA). We observed peaked responses of transpiration to VPD in all seedlings, and the optimum VPD for transpiration (Dopt ) shifted proportionally with increasing chamber VPD. Warming increased mean water use of Carya by 140% and Quercus by 150%, but had no significant effect on water use of Acer. Increased water use of ring-porous species was attributed to (1) higher air T and (2) stomatal acclimation to VPD resulting in higher gs and more sensitive stomata, and thereby less efficient water use. Stomatal acclimation maintained homeostasis of leaf T and carbon gain despite increased VPD, revealing that short-term stomatal responses to VPD may not be representative of long-term exposure. Acclimation responses differ from expectations of decreasing gs with increasing VPD and may necessitate revision of current models based on this assumption. PMID- 27392308 TI - Climate-driven disparities among ecological interactions threaten kelp forest persistence. AB - The combination of ocean warming and acidification brings an uncertain future to kelp forests that occupy the warmest parts of their range. These forests are not only subject to the direct negative effects of ocean climate change, but also to a combination of unknown indirect effects associated with changing ecological landscapes. Here, we used mesocosm experiments to test the direct effects of ocean warming and acidification on kelp biomass and photosynthetic health, as well as climate-driven disparities in indirect effects involving key consumers (urchins and rock lobsters) and competitors (algal turf). Elevated water temperature directly reduced kelp biomass, while their turf-forming competitors expanded in response to ocean acidification and declining kelp canopy. Elevated temperatures also increased growth of urchins and, concurrently, the rate at which they thinned kelp canopy. Rock lobsters, which are renowned for keeping urchin populations in check, indirectly intensified negative pressures on kelp by reducing their consumption of urchins in response to elevated temperature. Overall, these results suggest that kelp forests situated towards the low latitude margins of their distribution will need to adapt to ocean warming in order to persist in the future. What is less certain is how such adaptation in kelps can occur in the face of intensifying consumptive (via ocean warming) and competitive (via ocean acidification) pressures that affect key ecological interactions associated with their persistence. If such indirect effects counter adaptation to changing climate, they may erode the stability of kelp forests and increase the probability of regime shifts from complex habitat-forming species to more simple habitats dominated by algal turfs. PMID- 27392309 TI - Structural studies of a polysaccharide from Vibrio parahaemolyticus strain AN 16000. AB - The structure of a polysaccharide from Vibrio parahaemolyticus strain AN-16000 has been investigated. The sugar and absolute configuration analysis revealed d Glc, d-GalN, d-QuiN and l-FucN as major components. The PS was subjected to dephosphorylation with aqueous 40% HF to obtain an oligosaccharide that was analyzed by (1)H and (13)C NMR spectroscopy. The HR-MS spectrum of the oligosaccharide revealed a pentasaccharide composed of two Glc residues, one QuiNAc and one GalNAc, one FucNAc, as well as a glycerol moiety. The structure of the PS was determined using (1)H, (13)C, (15)N and (31)P NMR spectroscopy; inter residue correlations were identified by (1)H,(13)C-heteronuclear multiple-bond correlation, (1)H,(1)H-NOESY and (1)H,(31)P-hetero-TOCSY experiments. The PS backbone has the following teichoic acid-like structure: ->3)-d-Gro-(1-P-6)-beta d-Glcp-(1->4)-alpha-l-FucpNAc-(1->3)-beta-d-QuipNAc-(1-> with a side-chain consisting of alpha-d-Glcp-(1->6)-alpha-d-GalpNAc-(1-> linked to the O3 position of the FucNAc residue. PMID- 27392310 TI - Two novel methods to assess ulnar nerve conduction across the elbow. AB - PURPOSE: Nerve conduction studies (NCS) are used as an electrodiagnostic method for diagnosing ulnar neuropathy of the elbow (UNE). The purpose of this study was to determine normal and reliability values of across elbow ulnar nerve conduction velocity using two novel methods. METHODS: Ulnar nerve conduction studies were performed on both upper extremities of 104 healthy subjects. Two different techniques were used to evaluate ulnar nerve function at the elbow: Technique 1 (W-BE-AE) determined mixed NCV across the elbow indirectly while Technique 2 (BE AE) measured conduction time directly. Twenty subjects returned within one week for re-testing to generate reliability data. RESULTS: The mean NCV for the BE-AE segment using Technique 1 was 59.68m/s (+/-8.91m/s). The mean peak latency for the BE-AE segment using Technique 2 was 2.03ms (+/-0.24ms). The interrater and intrarater reliability intraclass correlation coefficient (ICC) for Technique 1 was 0.454 and 0.756, respectively. For Technique 2, the interrater and intrarater reliability ICC was 0.76 and 0.814, respectively. CONCLUSION: This study identified normal values for ulnar nerve conduction across the elbow with reliability ranging from poor to good, depending on the technique. These two novel techniques provide alternative methods to traditional techniques to measure ulnar nerve conduction across the elbow. PMID- 27392311 TI - The Tyrosine Kinome Dictates Breast Cancer Heterogeneity and Therapeutic Responsiveness. AB - Phospho-tyrosine signaling networks control numerous biological processes including cellular differentiation, cell growth and survival, motility, and invasion. Aberrant regulation of the tyrosine kinome is a hallmark of malignancy and influences all stages of breast cancer progression, from initiation to the development of metastatic disease. The success of specific tyrosine kinase inhibitors strongly validates the clinical relevance of tyrosine phosphorylation networks in breast cancer pathology. However, a significant degree of redundancy exists within the tyrosine kinome. Numerous receptor and cytoplasmic tyrosine kinases converge on a core set of signaling regulators, including adaptor proteins and tyrosine phosphatases, to amplify pro-tumorigenic signal transduction pathways. Mutational activation, amplification, or overexpression of one or more components of the tyrosine kinome represents key contributing events responsible for the tumor heterogeneity that is observed in breast cancers. It is this molecular heterogeneity that has become the most significant barrier to durable clinical responses due to the development of therapeutic resistance. This review focuses on recent literature that supports a prominent role for specific components of the tyrosine kinome in the emergence of unique breast cancer subtypes and in shaping breast cancer plasticity, sensitivity to targeted therapies, and the eventual emergence of acquired resistance. J. Cell. Biochem. 117: 1971-1990, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27392312 TI - Modulation of the Isoprenoid/Cholesterol Biosynthetic Pathway During Neuronal Differentiation In Vitro. AB - During differentiation, neurons acquire their typical shape and functional properties. At present, it is unclear, whether this important developmental step involves metabolic changes. Here, we studied the contribution of the mevalonate (MVA) pathway to neuronal differentiation using the mouse neuroblastoma cell line N1E-115 as experimental model. Our results show that during differentiation, the activity of 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR), a key enzyme of MVA pathway, and the level of Low Density Lipoprotein receptor (LDLr) decrease, whereas the level of LDLr-related protein-1 (LRP1) and the dimerization of Scavanger Receptor B1 (SRB-1) rise. Pharmacologic inhibition of HMGR by simvastatin accelerated neuronal differentiation by modulating geranylated proteins. Collectively, our data suggest that during neuronal differentiation, the activity of the MVA pathway decreases and we postulate that any interference with this process impacts neuronal morphology and function. Therefore, the MVA pathway appears as an attractive pharmacological target to modulate neurological and metabolic symptoms of developmental neuropathologies. J. Cell. Biochem. 117: 2036-2044, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27392313 TI - Human Umbilical Cord Wharton's Jelly Stem Cell Conditioned Medium Induces Tumoricidal Effects on Lymphoma Cells Through Hydrogen Peroxide Mediation. AB - Several groups have reported that human umbilical cord Wharton's jelly stem cells (hWJSCs) possess unique tumoricidal properties against many cancers. However, the exact mechanisms as to how hWJSCs inhibit tumor growth are not known. Recent evidence suggests that exposure of cancer cells to high hydrogen peroxide (H2 O2 ) levels from H2 O2 -releasing drugs causes their death. We therefore explored whether the tumoricidal effect of hWJSCs on lymphoma cells was mediated via H2 O2 . We first exposed lymphoma cells to six different molecular weight cut-off (MWCO) concentrates of hWJSC-conditioned medium (hWJSC-CM) (3, 5, 10, 30, 50, 100 kDa) for 48 h. Since, the 3 kDa-MWCO concentrate showed the greatest cell inhibition we then investigated whether the tumoricidal effect of the specific 3 kDa-MWCO concentrate on two different lymphoma cell lines (Ramos and Toledo) was mediated via accumulation of H2 O2 . We used a battery of assays (MTT, propidium iodide, mitochondria membrane potential, apoptosis, cell cycle, oxidative stress enzymes, hydrogen peroxide, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation) to test this mechanism. The hWJSC-CM 3 kDa MWCO concentrate significantly decreased cell viability and mitochondrial membrane potential and increased cell death and apoptosis in both lymphoma cell lines. There were significant increases in superoxide dismutase with concomitant decreases in glutathione peroxidase, catalase, and thioredoxin peroxidase activities. H2 O2 levels, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation were also significantly increased in both lymphoma cell lines. The results suggested that the hWJSC-CM-3 kDa MWCO concentrate regulates cellular H2 O2 leading to a tumoricidal effect and may thus be a promising anti-lymphoma agent. J. Cell. Biochem. 117: 2045-2055, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27392315 TI - Health Literacy among Youth in Guatemala City. AB - Health literacy (HL) is recognized as an important health construct that is correlated with various health-related outcomes, but outside of the United States there is limited HL research available, particularly among youth. This study looked at the HL and harmful health behavior (i.e., substance use) of 210 youth across 10 schools in Guatemala City. Based on results from the Newest Vital Sign (NVS) HL assessment, fewer than one third of youth sampled had adequate HL. Training/education to improve adolescent HL is needed in Guatemala City, and the unique skillset of social workers could be an idea method of reaching at-risk youth. PMID- 27392316 TI - Beat-to-beat variability of fetal myocardial performance index. AB - OBJECTIVES: To determine whether there is beat-to-beat (BTB) variability in the fetal left myocardial performance index (MPI), as evaluated by an automated system, and whether there is a correlation between MPI and fetal heart rate (FHR). METHODS: This was a prospective cross-sectional study of uncomplicated, morphologically normal, singleton pregnancies at 20-38 weeks' gestation. Multiple cineloops for left MPI measurement were acquired during a single examination of each fetus. Raw cineloop data were analyzed by our automated MPI system (intraclass correlation coefficient of 1.0 for any given waveform) to produce a set of MPIs. The corresponding instantaneous FHR was measured for each individual cardiac cycle for which MPI was calculated. RESULTS: Data from 29 fetuses were analyzed; mean MPI was 0.52, mean FHR was 150 beats per min and the median number of cardiac cycles examined per fetus was 70 (interquartile range, 31-115). Marked BTB variability was noted; median coefficient of variation was 10% (range, 5.5 13.9%). FHR was weakly correlated with absolute MPI (r = 0.22; P < 0.05). BTB variation in MPI as a percentage of the mean MPI was not significantly correlated with FHR (r = 0.031; P = 0.146). When standard error of the mean of all MPI values was divided by the mean for each case, it showed that at least four cardiac cycles should be averaged to reduce MPI variability to approximately +/- 5%. CONCLUSION: There is significant BTB variability in fetal left MPI, which has an overall weak correlation with FHR. This could be a factor affecting the consistency of MPI values reported by different research groups. Variability would be reduced by averaging 4-5 cardiac cycles per fetus. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27392318 TI - Access to Pyrazolidin-3,5-diones through Anodic N-N Bond Formation. AB - Pyrazolidin-3,5-diones are important motifs in heterocyclic chemistry and are of high interest for pharmaceutical applications. In classic organic synthesis, the hydrazinic moiety is installed through condensation using the corresponding hydrazine building blocks. However, most N,N'-diaryl hydrazines are toxic and require upstream preparation owing to their low commercial availability. We present an alternative and sustainable synthetic approach to pyrazolidin-3,5 diones that employs readily accessible dianilides as precursors, which are anodically converted to furnish the N-N bond. The electroconversion is conducted in a simple undivided cell under constant-current conditions. PMID- 27392317 TI - Complicated community acquired pneumonia in childhood: Different types, clinical course, and outcome. AB - : The incidence of pediatric community acquired complicated pneumonia (PCACP) is increasing. Questions addressed: Are different types of PCACP one disease? How do different treatment protocols affect the outcome? METHODS: Retrospective analysis of medical records of PCACP hospitalizations in the three major hospitals in Jerusalem in the years 2001-2010 for demographics, clinical presentation, management, and outcome. RESULTS: Of the 144 children (51% aged 1-4 years), 91% of Jewish origin; 40% had para-pneumonic effusion (PPE), 40% empyema (EMP), and 20% necrotizing pneumonia (NP). Bacterial origin was identified in 42% (empyema 79%, P = 0.009), most common S. pneumoniae (32%), group A streptococcus (9%). Patients with EMP, compared to PPE and NP, were less likely to receive prior antibiotic treatment (35% vs. 57% and 59%, respectively, P = 0.04). Mean hospitalization was longer in patients with NP followed by EMP and PPE (16.4 +/- 10.6, 15.2 +/- 7.9, and 12.7 +/- 4.7 days, respectively), use of fibrinolysis was not associated with the outcome. All children had recovered to discharge regardless of antibiotic therapy or fibrinolysis. ANSWER: NP is a more severe disease with prolonged morbidity and hospitalization in spite of prior antibiotic treatment. All types had favorable outcome regardless of treatment-protocol. Complicated pneumonia has an ethnic predominance. Pediatr Pulmonol. 2017;52:247 254. (c) 2016 Wiley Periodicals, Inc. PMID- 27392319 TI - Detection of prognostic factors in children and adolescents with Burkitt and Diffuse Large B-Cell Lymphoma treated with the AIEOP LNH-97 protocol. AB - Burkitt lymphoma (BL) and Diffuse Large B-Cell Lymphoma (DLBCL) account for most cases of non-Hodgkin lymphoma (NHL) in childhood. We report the clinical characteristics, outcome and prognostic factors in children with BL or DLBCL treated according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) LNH-97 protocol. Patients aged up to 18 years that were newly diagnosed with BL/DLBCL were included in the study. Therapy consisted of pre-phase followed by 2-6 high-dose chemotherapy courses tailored according to lactate dehydrogenase (LDH) value and disease stage. A total of 442 patients (379 BL, 63 DLBCL) were enrolled between 1997 and 2014, of whom 18 failed to achieve remission, 6 experienced treatment-related death, 2 developed second malignancy and 20 relapsed. At a median follow-up time of 5 years, overall survival was 93% (+/-1%) and event-free survival was 90% (+/-1%). LDH value above the median value had an independently negative prognostic value (P < 0.0001). However, in the subgroup of 128 patients in which minimal disseminated disease (MDD) was analysed, MDD positivity became the only unfavourable prognostic factor for progression-free survival. Tailored chemotherapy could be extremely effective with limited toxicity. Identification of MDD as a hallmark of a higher risk of treatment failure may provide a target population for treatment intensification by anti CD20. PMID- 27392320 TI - Prenatal observation of nystagmus, cataracts, and brain abnormalities in a case of Zellweger spectrum disorder syndrome. PMID- 27392321 TI - Degradation behavior of, and tissue response to photo-crosslinked poly(trimethylene carbonate) networks. AB - Photo-crosslinked networks prepared from three-armed methacrylate functionalized PTMC oligomers (PTMC-tMA macromers) are attractive materials for developing an anatomically correct meniscus scaffold. In this study, we evaluated cell specific biocompatibility, in vitro and in vivo degradation behavior of, and tissue response to, such PTMC networks. By evaluating PTMC networks prepared from PTMC tMA macromers of different molecular weights, we were able to assess the effect of macromer molecular weight on the degradation rate of the PTMC network obtained after photo-crosslinking. Three photo-crosslinked networks with different crosslinking densities were prepared using PTMC-tMA macromers with molecular weights 13.3, 17.8, and 26.7 kg/mol. Good cell biocompatibility was demonstrated in a proliferation assay with synovium derived cells. PTMC networks degraded slowly, but statistically significant, both in vitro as well as subcutaneously in rats. Networks prepared from macromers with higher molecular weights demonstrated increased degradation rates compared to networks prepared from initial macromers of lowest molecular weight. The degradation process took place via surface erosion. The PTMC networks showed good tissue tolerance during subcutaneous implantation, to which the tissue response was characterized by the presence of fibrous tissue and encapsulation of the implants. Concluding, we developed cell and tissue biocompatible, photo-crosslinked PTMC networks using PTMC-tMA macromers with relatively high molecular weights. These photo-crosslinked PTMC networks slowly degrade by a surface erosion process. Increasing the crosslinking density of these networks decreases the rate of surface degradation. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2823-2832, 2016. PMID- 27392322 TI - Mechanistic Aspects of Phosphate Diester Cleavage Assisted by Imidazole. A Template Reaction for Obtaining Aryl Phosphoimidazoles. AB - Phosphoimidazole-containing compounds are versatile players in biological and chemical processes. We explore catalytic and mechanistic criteria for the efficient formation of cyclic aryl phosphoimidazoles in aqueous solution, viewed as a template reaction for the in situ synthesis of related compounds. To provide a detailed analysis for this reaction a series of o-(2'-imidazolyl)naphthyl (4 nitrophenyl) phosphate isomers were examined to provide a basis for analysis of both mechanism and the influence of structural factors affecting the nucleophilic attack of the imidazolyl group on the phosphorus center of the substrate. Formation of the cyclic aryl phosphoimidazoles was probed by NMR and ESI-MS techniques. Kinetic experiments show that cyclization is faster under alkaline conditions, with an effective molarity up to 2900 M for the imidazolyl group, ruling out competition from external nucleophiles. Heavy atom isotope effect and computational studies show that the reaction occurs through a SN2(P)-type mechanism involving a pentacoordinated phosphorus TS, with apical positions occupied by the incoming imidazolyl nucleophile and the p-nitrophenolate leaving group. The P-O bond to the leaving group is about 50-60% broken in the transition state. PMID- 27392323 TI - Crown group Oxyphotobacteria postdate the rise of oxygen. AB - The rise of oxygen ca. 2.3 billion years ago (Ga) is the most distinct environmental transition in Earth history. This event was enabled by the evolution of oxygenic photosynthesis in the ancestors of Cyanobacteria. However, long-standing questions concern the evolutionary timing of this metabolism, with conflicting answers spanning more than one billion years. Recently, knowledge of the Cyanobacteria phylum has expanded with the discovery of non-photosynthetic members, including a closely related sister group termed Melainabacteria, with the known oxygenic phototrophs restricted to a clade recently designated Oxyphotobacteria. By integrating genomic data from the Melainabacteria, cross calibrated Bayesian relaxed molecular clock analyses show that crown group Oxyphotobacteria evolved ca. 2.0 billion years ago (Ga), well after the rise of atmospheric dioxygen. We further estimate the divergence between Oxyphotobacteria and Melainabacteria ca. 2.5-2.6 Ga, which-if oxygenic photosynthesis is an evolutionary synapomorphy of the Oxyphotobacteria-marks an upper limit for the origin of oxygenic photosynthesis. Together, these results are consistent with the hypothesis that oxygenic photosynthesis evolved relatively close in time to the rise of oxygen. PMID- 27392324 TI - Application of the PrevenaTM Incision Management System Following Complex Ventral Hernia Repairs with Abdominal Wall Reconstruction. AB - Surgical site infections (SSIs) are a drain on the healthcare economy. A recent development for the primary prevention of wound infections is the use of negative pressure wound therapy (NPWT) on closed wounds. The PrevenaTM Incision Management System (KCI USA, Inc., San Antonio, TX) is a new NPWT designed for application on closed surgical incisions in order to prevent potential wound-related complications. We evaluated the use of this new technology on large abdominal incisions following complex ventral hernia repairs with abdominal wall reconstruction in patients with risk factors for developing wound complications and conducted a review of the current literature pertaining to the use of NPWT on closed incisions. PMID- 27392325 TI - Key roles of EMT for adaptive resistance to MEK inhibitor in KRAS mutant lung cancer. AB - KRAS is frequently mutated in a variety of cancers including lung cancer. Whereas the mitogen-activated protein kinase (MAPK) is a well-known effector pathway of KRAS, blocking this pathway with MEK inhibitors is relatively ineffective. One major contributor to limited efficacy is attributed to the reactivation of MAPK signal following MEK inhibition by multiple feedback mechanisms. In a recent study, we have identified that epithelial-to-mesenchymal transition defines feedback activation of receptor tyrosine kinase signaling following MEK inhibition in KRAS mutant lung cancer. In epithelial-like cells, this feedback was mediated by ERBB3. In contrast, in mesenchymal-like cells, the feedback was attributed to the fibroblast growth factor receptor 1 (FGFR1) pathway. FGFR1 was dominantly expressed in mesenchymal-like cells: suppression of SPRY proteins by MEK inhibition relieved negative feedback control of basal FGFR-FRS2 function, resulting in reactivation of MAPK signaling via FGFR1. Therapeutically, the combination of MEK inhibitor trametinib with an FGFR inhibitor induced tumor regressions in tumor xenografts derived from mesenchymal-like KRAS mutant cancer cell lines as well as a patient derived xenograft model with a representative mesenchymal phenotype. Collectively, feedback activation of MAPK by FGFR1 signaling mitigates the effect of MEK inhibitor in mesenchymal-like KRAS mutant lung tumors, and combinations of clinically available FGFR1 inhibitors and MAPK inhibitors constitute a therapeutic approach to treat these cancers effectively. PMID- 27392326 TI - Experimental study showed that adding fortifier and extra-hydrolysed proteins to preterm infant mothers' milk increased osmolality. AB - AIM: Measuring milk osmolality after adjustable fortification is clinically relevant, as values exceeding recommended safety thresholds might result in gastrointestinal consequences. The aim of this study was to evaluate the effect of four fortification levels and storage time on the osmolality of human milk. METHODS: This was an experimental study using 71 spare samples of fresh breastmilk collected from 31 mothers of preterm infants. Osmolality was measured before and after adding commercial human milk fortifier containing dextrinomaltose and hydrolysed proteins at four different concentrations. Measurements were performed at various points during the 23 hours after fortification. RESULTS: The mean basal osmolality of the 71 human milk samples was 296 +/- 14 milliosmoles (mOsm)/kg, and these remained stable over a period of 23 hours. Just after fortification, the four fortified formulas showed higher osmolalities than the nonfortified human milk, ranging between 384 +/- 14 and 486 +/- 15 mOsm/kg, respectively (p < 0.01). This osmolality increased significantly from 20 minutes to 23 hours after fortification (p < 0.05). CONCLUSION: Adding fortifier and extra-hydrolysed proteins to human preterm milk increased osmolality, and these osmolality levels also increased with time. We recommend evaluating the risk of hyperosmolality when a higher fortification level is needed, to avoid gastrointestinal problems. PMID- 27392327 TI - Withdrawal Statement: Protein Kinase C Is Involved in the Induction of ATP Binding Cassette Transporter A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human Macrophages by Huwait, E.A., Singh, N.N., Michael, D.R., Davies, T.S., Moss, J.W.E., and Ramji, D.P. PMID- 27392328 TI - Correction to: Measuring Effortful Control Using the Children's Behavior Questionnaire-Very Short Form: Modeling Matters. PMID- 27392329 TI - Catechols as Sources of Hydrogen Atoms in Radical Deiodination and Related Reactions. AB - When used with trialkylboranes, catechol derivatives, which are low-cost and low toxicity, are valuable hydrogen atom donors for radical chain reactions involving alkyl iodides and related radical precursors. The system 4-tert butylcatechol/triethylborane has been used to reduce a series of secondary and tertiary iodides, a xanthate, and a thiohydroxamate ester. Catechol derivatives are right in the optimal kinetic window for synthetic applications, as demonstrated by highly efficient radical cyclizations. Cyclizations leading to the formation of quaternary centers can be performed in an all-at-once process (no slow addition of the hydrogen atom donor) at standard concentrations. The H donor properties of catechol derivatives can be fine-tuned by changing their substitution pattern. In slow radical cyclization processes, an enhanced ratio of cyclized/uncyclized products was obtained by using 3-methoxycatechol instead of 4 tert-butylcatechol. PMID- 27392330 TI - Implications of fluoroquinolone contamination for the aquatic environment-A review. AB - Until recently, the behaviors of antibiotics and their ecotoxicological impact have been overlooked in the environment. The topic is broad and encompasses a wide range of organisms including microorganisms, algae, invertebrates, and vertebrates inhabiting various aquatic ecosystems. Changing the equilibrium of any 1 component in such systems disrupts the balance of the whole system. The manufacturing and frequent use of fluoroquinolones in human and animal medicine raises great concern over the increase of antibiotic resistance prevalence in microorganisms; however, in addition, the fate of antibiotic parent and metabolite compounds entering environmental ecosystems through various pathways raises environmental impact concerns. Research has focused on the concentration of antibiotics present in environmental samples and the acute toxicity to organisms by way of animal assessment models; however, it remains unclear what role low-level chronic exposure plays in ecotoxicological effects on lifeforms in aquatic environments. The aim of the present review was to assess the levels of fluorquinolone use in animal and human medicine, to determine the pathways of dissemination, and to highlight the ecotoxicological implications in freshwater environments. Environ Toxicol Chem 2016;35:2647-2656. (c) 2016 SETAC. PMID- 27392331 TI - Learning to Work with Trauma Survivors: Lessons from Tbilisi, Georgia. AB - Survivors of armed conflict may experience traumatic stress, psychological symptoms, distress, or other behavioral health issues related to the disaster of war. This article outlines the historical background of the Russian-Georgian war, details the implementation of social work in the developing country of Georgia, and describes the training and application of social work knowledge and values using macro and micro examples of interventions that provide Masters of social work students and social workers with tools to address the needs of refugees affected by disaster. Following the macro- and microexamples, pedagogy and implications for social workers and social work students working with victims of trauma with few available resources are discussed. PMID- 27392332 TI - Global change impacts on river ecosystems: A high-resolution watershed study of Ebro river metabolism. AB - Global change is transforming freshwater ecosystems, mainly through changes in basin flow dynamics. This study assessed how the combination of climate change and human management of river flow impacts metabolism of the Ebro River (the largest river basin in Spain, 86,100km(2)), assessed as gross primary production GPP-and ecosystem respiration-ER. In order to investigate the influence of global change on freshwater ecosystems, an analysis of trends and frequencies from 25 sampling sites of the Ebro river basin was conducted. For this purpose, we examined the effect of anthropogenic flow control on river metabolism with a Granger causality study; simultaneously, took into account the effects of climate change, a period of extraordinary drought (largest in past 140years). We identified periods of sudden flow changes resulting from both human management and global climate effects. From 1998 to 2012, the Ebro River basin was trending toward a more autotrophic condition indicated by P/R ratio. Particularly, the results show that floods that occurred after long periods of low flows had a dramatic impact on the respiration (i.e., mineralization) capacity of the river. This approach allowed for a detailed characterization of the relationships between river metabolism and drought impacts at the watershed level. These findings may allow for a better understanding of the ecological impacts provoked by flow management, thus contributing to maintain the health of freshwater communities and ecosystem services that rely on their integrity. PMID- 27392333 TI - Effect of flood events on transport of suspended sediments, organic matter and particulate metals in a forest watershed in the Basque Country (Northern Spain). AB - An understanding of the processes controlling sediment, organic matter and metal export is critical to assessing and anticipating risk situations in water systems. Concentrations of suspended particulate matter (SPM), dissolved (DOC) and particulate (POC) organic carbon and metals (Cu, Ni, Pb, Cr, Zn, Mn, Fe) in dissolved and particulate phases were monitored in a forest watershed in the Basque Country (Northern Spain) (31.5km(2)) over three hydrological years (2009 2012), to evaluate the effect of flood events on the transport of these materials. Good regression was found between SPM and particulate metal concentration, making it possible to compute the load during the twenty five flood events that occurred during the study period at an annual scale. Particulate metals were exported in the following order: Fe>Mn>Zn>Cr>Pb>Cu>Ni. Annual mean loads of SPM, DOC and POC were estimated at 2267t, 104t and 57t, respectively, and the load (kg) of particulate metals at 76 (Ni), 83 (Cu), 135 (Pb), 256 (Cr), 532 (Zn), 1783 (Mn) and 95170 (Fe). Flood events constituted 91% SPM, 65%-DOC, 71%-POC, 80%-Cu, 85%-Ni, 72%-Pb, 84%-Cr, 74%-Zn, 87%-Mn and 88%-Fe of total load exported during the three years studied. Flood events were classified into three categories according to their capacity for transporting organic carbon and particulate metals. High intensity flood events are those with high transport capacity of SPM, organic carbon and particulate metals. Most of the SPM, DOC, POC and particulate metal load was exported by this type of flood event, which contributed 59% of SPM, 45% of organic carbon and 54% of metals. PMID- 27392335 TI - Development of a conceptual framework of holistic risk assessment - Landfill as a particular type of contaminated land. AB - Landfills can be regarded as a particular type of contaminated land that has a potential to directly and indirectly pollute all of the four main spheres of the environment which are the lithosphere, atmosphere, hydrosphere and eventually adversely impact the biosphere. Therefore, environmental risk assessment of a landfill has to be more integrated and holistic by virtue of its nature of being a multidimensional pollutant source. Despite this, although various risk assessment approaches have been adopted for landfill waste disposal sites, there are still wide-ranging knowledge gaps and limitations which need to be addressed. One important knowledge gap and limitation of current risk assessment approaches is the inability to fully identify, categorise and aggregate all individual risks from all combinations of hazards, pathways and targets/receptors (e.g. water, air, soil and biota) in connection to a certain landfill leachate and yet at any stage of the landfill cycle. So such an approach is required that could not only integrate all possible characteristics of varying scenarios but also contain the ability to establish an overall risk picture, irrespective of the lifecycle stage of the landfill (e.g. planning stage/pre-operation, in-operation or post operation/closed). One such approach to address the wide-breadth of landfill impact risks is by developing a more holistic risk assessment methodology, whose conceptual framework is presented in this paper for landfill leachate in a whole system format. This conceptual framework does not only draw together various constituting factors and sub-factors of risk assessment in a logical sequence and categorical order, but also indicates the "what, why, when and how" outputs of and inputs to these factors and sub-factors can be useful. The framework is designed to identify and quantify a range of risks associated with all stages of the landfill lifecycle, and yet in a more streamlined, logical, categorical and integrated format, offering a more standardised and unified whole-system approach. PMID- 27392334 TI - Addressing the local aspects of global change impacts on stream metabolism using frequency analysis tools. AB - Global change, as a combination of climate change, human activities on watersheds and the river flow regulation, causes intense changes in hydrological cycles and, consequently, threatens the good ecological status of freshwater biological communities. This study addresses how and whether the combination of climatic drivers and local human impacts may alter the metabolism of freshwater communities. We identified a few factors modulating the natural water flow and quality in 25 point spread within the Ebro river Basin: waste water spills, industrial spills, reservoir discharges, water withdrawals, agricultural use, and the presence of riparian forests. We assessed their impacts on the freshwater metabolism as changes in the annual cycle of both gross primary production-GPP - and ecosystem respiration-ER -. For this purpose, daily data series were analyzed by continuous wavelet transformation, allowing for the assessment of the metabolic ecosystem Frequency Spectrum Patterns (FSPs). Changes in the behavior of ecosystem metabolism were strongly associated with local characteristics at each sampling point, however in 20 out of 25 studied points, changes in metabolic ecosystem FSP were related to climatic change events (the driest period of the last 140years). The changes in FSP indicate that severe impacts on how biological communities use carbon sources occur as a result of the human water management - too much focus on human needs - during intense climatic events. Results show that local factors, and specially the flow regulation, may modulate the impact of global change. As example those points exposed to a more intense anthropization showed a clear disruption - and even disappearance - of the annual FSP. This information may help managers to understand the action mechanisms of non-climatic factors at ecosystem level, leading to better management policies based on the promotion of ecosystem resilience. The method here presented may help on improving the calculation of ecological flows to maintain the river metabolic annual cycles as close as possible to the natural ones. PMID- 27392336 TI - Biological hazard evaluation of a pharmaceutical effluent before and after a photo-Fenton treatment. AB - The aim of this study was to evaluate the biological hazard of a pharmaceutical effluent before and after treatment. For the former, the determined 96h-LC50 value was 1.2%. The photo-Fenton treatment catalyzed with an iron-pillared clay reduced this parameter by 341.7%. Statistically significant increases with respect to the control group (P<0.05) were observed at 12, 24, 48 and 72h in HPC (50.2, 30.4, 66.9 and 43.3%), LPX (22, 83.2, 62.7 and 59.5%) and PCC (14.6, 23.6, 24.4 and 25.6%) and antioxidant enzymes SOD (29.4, 38.5, 32.7 and 49.5%) and CAT (48.4, 50.3, 38.8 and 46.1%) in Hyalella azteca before treatment. Also increases in damage index were observed before treatment of 53.1, 59.9, 66.6 and 72.1% at 12, 24, 48 and 72h, respectively. After treatment the same biomarkers of oxidative stress decreased with respect to before treatment being to HPC (29.3, 22.5, 41.6 and 31.7%); LPX (14.2, 43.1, 30.7 and 35.5%); PCC (12.6, 21.3, 24.2 and 23.9%); SOD (39.2, 33.9, 49.5 and 37.9%) and CAT (28.6, 35.8, 33.7 and 31.7) at 12, 24, 48 and 72h, respectively (P<0.05). The damage index were decreased at 12, 24, 48 and 72h in 48.9, 57.8, 67.3 and 72.1%, respectively. In conclusion, the obtained results demonstrate the need of performing bioassays in order to characterize an effluent before discharge and not base such a decision only upon current normativity. In addition, it was also concluded that the heterogeneous photo-Fenton process decreases the presence of PCT, oxidative stress, genotoxic damage and LC50 in Hyalella azteca. PMID- 27392338 TI - Patient-Specific Finite-Element Simulation of the Insertion of Guidewire During an EVAR Procedure: Guidewire Position Prediction Validation on 28 Cases. AB - OBJECTIVE: Validation of a numerical method to compute arterial deformations under the insertion of an "extra-siff" guidewire during Endovascular Repair of Abdominal Aortic Aneurysm. METHODS: We propose the validation of a previously developed simulation method. The model is calibrated using anatomical hypothesis and intraoperative observations. Simulation results are blindly evaluated against 3-D imaging data acquired during the surgical procedure on 28 patients, based on the predicted position of the intraoperative guidewire. RESULTS: Simulation was successfully conducted on the 28 patients. The mean position error given by the Modified Hausdorff Distance for the 28 cases was 3.8 +/- 1.9 mm, which demonstrates very good results for most of the cases. CONCLUSION: The work reported here shows that numerical simulation can predict some rather large variations in the vascular geometry due to tools insertion, for a wide variety of aorto-iliac morphologies. This is a new step toward clinically applicable mechanical simulation. SIGNIFICANCE: Validation on 3-D intraoperative data on a large number of cases-robustness on adverse anatomies. PMID- 27392339 TI - EEG-Informed Attended Speaker Extraction From Recorded Speech Mixtures With Application in Neuro-Steered Hearing Prostheses. AB - OBJECTIVE: We aim to extract and denoise the attended speaker in a noisy two speaker acoustic scenario, relying on microphone array recordings from a binaural hearing aid, which are complemented with electroencephalography (EEG) recordings to infer the speaker of interest. METHODS: In this study, we propose a modular processing flow that first extracts the two speech envelopes from the microphone recordings, then selects the attended speech envelope based on the EEG, and finally uses this envelope to inform a multichannel speech separation and denoising algorithm. RESULTS: Strong suppression of interfering (unattended) speech and background noise is achieved, while the attended speech is preserved. Furthermore, EEG-based auditory attention detection (AAD) is shown to be robust to the use of noisy speech signals. CONCLUSIONS: Our results show that AAD-based speaker extraction from microphone array recordings is feasible and robust, even in noisy acoustic environments, and without access to the clean speech signals to perform EEG-based AAD. SIGNIFICANCE: Current research on AAD always assumes the availability of the clean speech signals, which limits the applicability in real settings. We have extended this research to detect the attended speaker even when only microphone recordings with noisy speech mixtures are available. This is an enabling ingredient for new brain-computer interfaces and effective filtering schemes in neuro-steered hearing prostheses. Here, we provide a first proof of concept for EEG-informed attended speaker extraction and denoising. PMID- 27392337 TI - Full-Body Musculoskeletal Model for Muscle-Driven Simulation of Human Gait. AB - OBJECTIVE: Musculoskeletal models provide a non-invasive means to study human movement and predict the effects of interventions on gait. Our goal was to create an open-source 3-D musculoskeletal model with high-fidelity representations of the lower limb musculature of healthy young individuals that can be used to generate accurate simulations of gait. METHODS: Our model includes bony geometry for the full body, 37 degrees of freedom to define joint kinematics, Hill-type models of 80 muscle-tendon units actuating the lower limbs, and 17 ideal torque actuators driving the upper body. The model's musculotendon parameters are derived from previous anatomical measurements of 21 cadaver specimens and magnetic resonance images of 24 young healthy subjects. We tested the model by evaluating its computational time and accuracy of simulations of healthy walking and running. RESULTS: Generating muscle-driven simulations of normal walking and running took approximately 10 minutes on a typical desktop computer. The differences between our muscle-generated and inverse dynamics joint moments were within 3% (RMSE) of the peak inverse dynamics joint moments in both walking and running, and our simulated muscle activity showed qualitative agreement with salient features from experimental electromyography data. CONCLUSION: These results suggest that our model is suitable for generating muscle-driven simulations of healthy gait. We encourage other researchers to further validate and apply the model to study other motions of the lower extremity. SIGNIFICANCE: The model is implemented in the open-source software platform OpenSim. The model and data used to create and test the simulations are freely available at https://simtk.org/home/full_body/, allowing others to reproduce these results and create their own simulations. PMID- 27392340 TI - Observer-Based Human Knee Stiffness Estimation. AB - OBJECTIVE: We consider the problem of stiffness estimation for the human knee joint during motion in the sagittal plane. METHODS: The new stiffness estimator uses a nonlinear reduced-order biomechanical model and a body sensor network (BSN). The developed model is based on a two-dimensional knee kinematics approach to calculate the angle-dependent lever arms and the torques of the muscle-tendon complex. To minimize errors in the knee stiffness estimation procedure that result from model uncertainties, a nonlinear observer is developed. The observer uses the electromyogram (EMG) of involved muscles as input signals and the segmental orientation as the output signal to correct the observer-internal states. Because of dominating model nonlinearities and nonsmoothness of the corresponding nonlinear functions, an unscented Kalman filter is designed to compute and update the observer feedback (Kalman) gain matrix. RESULTS: The observer-based stiffness estimation algorithm is subsequently evaluated in simulations and in a test bench, specifically designed to provide robotic movement support for the human knee joint. CONCLUSION: In silico and experimental validation underline the good performance of the knee stiffness estimation even in the cases of a knee stiffening due to antagonistic coactivation. SIGNIFICANCE: We have shown the principle function of an observer-based approach to knee stiffness estimation that employs EMG signals and segmental orientation provided by our own IPANEMA BSN. The presented approach makes realtime, model-based estimation of knee stiffness with minimal instrumentation possible. PMID- 27392342 TI - DeepID-Net: Deformable Deep Convolutional Neural Networks for Object Detection. AB - In this paper, we propose deformable deep convolutional neural networks for generic object detection. This new deep learning object detection framework has innovations in multiple aspects. In the proposed new deep architecture, a new deformation constrained pooling (def-pooling) layer models the deformation of object parts with geometric constraint and penalty. A new pre-training strategy is proposed to learn feature representations more suitable for the object detection task and with good generalization capability. By changing the net structures, training strategies, adding and removing some key components in the detection pipeline, a set of models with large diversity are obtained, which significantly improves the effectiveness of model averaging. The proposed approach improves the mean averaged precision obtained by RCNN [16], which was the state-of-the-art, from 31% to 50.3% on the ILSVRC2014 detection test set. It also outperforms the winner of ILSVRC2014, GoogLeNet, by 6.1%. Detailed component wise analysis is also provided through extensive experimental evaluation, which provides a global view for people to understand the deep learning object detection pipeline. PMID- 27392343 TI - Joint Intermodal and Intramodal Label Transfers for Extremely Rare or Unseen Classes. AB - In this paper, we present a label transfer model from texts to images for image classification tasks. The problem of image classification is often much more challenging than text classification. On one hand, labeled text data is more widely available than the labeled images for classification tasks. On the other hand, text data tends to have natural semantic interpretability, and they are often more directly related to class labels. On the contrary, the image features are not directly related to concepts inherent in class labels. One of our goals in this paper is to develop a model for revealing the functional relationships between text and image features as to directly transfer intermodal and intramodal labels to annotate the images. This is implemented by learning a transfer function as a bridge to propagate the labels between two multimodal spaces. However, the intermodal label transfers could be undermined by blindly transferring the labels of noisy texts to annotate images. To mitigate this problem, we present an intramodal label transfer process, which complements the intermodal label transfer by transferring the image labels instead when relevant text is absent from the source corpus. In addition, we generalize the inter-modal label transfer to zero-shot learning scenario where there are only text examples available to label unseen classes of images without any positive image examples. We evaluate our algorithm on an image classification task and show the effectiveness with respect to the other compared algorithms. PMID- 27392344 TI - Best Fitting Hyperplanes for Classification. AB - In this paper, we propose novel methods that are more suitable than classical large-margin classifiers for open set recognition and object detection tasks. The proposed methods use the best fitting hyperplanes approach, and the main idea is to find the best fitting hyperplanes such that each hyperplane is close to the samples of one of the classes and is as far as possible from the other class samples. To this end, we propose two different classifiers: The first classifier solves a convex quadratic optimization problem, but negative samples can lie on one side of the best fitting hyperplane. The second classifier, however, allows the negative samples to lie on both sides of the fitting hyperplane by using concave-convex procedure. Both methods are extended to the nonlinear case by using the kernel trick. In contrast to the existing hyperplane fitting classifiers in the literature, our proposed methods are suitable for large-scale problems, and they return sparse solutions. The experiments on several databases show that the proposed methods typically outperform other hyperplane fitting classifiers, and they work as good as the SVM classifier in classical recognition tasks. However, the proposed methods significantly outperform SVM in open set recognition and object detection tasks. PMID- 27392345 TI - Consistent Spatial-Temporal Longitudinal Atlas Construction for Developing Infant Brains. AB - Brain atlases are an essential component in understanding the dynamic cerebral development, especially for the early postnatal period. However, longitudinal atlases are rare for infants, and the existing ones are generally limited by their fuzzy appearance. Moreover, since longitudinal atlas construction is typically performed independently over time, the constructed atlases often fail to preserve temporal consistency. This problem is further aggravated for infant images since they typically have low spatial resolution and insufficient tissue contrast. In this paper, we propose a novel framework for consistent spatial temporal construction of longitudinal atlases for developing infant brain MR images. Specifically, for preserving structural details, the atlas construction is performed in spatial-temporal wavelet domain simultaneously. This is achieved by a patch-based combination of results from each frequency subband. Compared with the existing infant longitudinal atlases, our experimental results indicate that our approach is able to produce longitudinal atlases with richer structural details and also better longitudinal consistency, thus leading to higher performance when used for spatial normalization of a group of infant brain images. PMID- 27392346 TI - TICMR: Total Image Constrained Material Reconstruction via Nonlocal Total Variation Regularization for Spectral CT. AB - This work develops a material reconstruction method for spectral CT, namely Total Image Constrained Material Reconstruction (TICMR), to maximize the utility of projection data in terms of both spectral information and high signal-to-noise ratio (SNR). This is motivated by the following fact: when viewed as a spectrally integrated measurement, the projection data can be used to reconstruct a total image without spectral information, which however has a relatively high SNR; when viewed as a spectrally-resolved measurement, the projection data can be utilized to reconstruct the material composition, which however has a relatively low SNR. The material reconstruction synergizes material decomposition and image reconstruction, i.e., the direct reconstruction of material compositions instead of a two-step procedure that first reconstructs images and then decomposes images. For material reconstruction with high SNR, we propose TICMR with nonlocal total variation (NLTV) regularization. That is, first we reconstruct a total image using spectrally-integrated measurement without spectral binning, and build the NLTV weights from this image that characterize nonlocal image features; then the NLTV weights are incorporated into a NLTV-based iterative material reconstruction scheme using spectrally-binned projection data, so that these weights serve as a high-SNR reference to regularize material reconstruction. Note that the nonlocal property of NLTV is essential for material reconstruction, since material compositions may have significant local intensity variations although their structural information is often similar. In terms of solution algorithm, TICMR is formulated as an iterative reconstruction method with the NLTV regularization, in which the nonlocal divergence is utilized based on the adjoint relationship. The alternating direction method of multipliers is developed to solve this sparsity optimization problem. The proposed TICMR method was validated using both simulated and experimental data. In comparison with FBP and total-variation-based iterative method, TICMR had improved image quality, e.g., contrast-to-noise ratio and spatial resolution. PMID- 27392347 TI - Noise-Compensated, Bias-Corrected Diffusion Weighted Endorectal Magnetic Resonance Imaging via a Stochastically Fully-Connected Joint Conditional Random Field Model. AB - Diffusion weighted magnetic resonance imaging (DW-MR) is a powerful tool in imaging-based prostate cancer screening and detection. Endorectal coils are commonly used in DW-MR imaging to improve the signal-to-noise ratio (SNR) of the acquisition, at the expense of significant intensity inhomogeneities (bias field) that worsens as we move away from the endorectal coil. The presence of bias field can have a significant negative impact on the accuracy of different image analysis tasks, as well as prostate tumor localization, thus leading to increased inter- and intra-observer variability. Retrospective bias correction approaches are introduced as a more efficient way of bias correction compared to the prospective methods such that they correct for both of the scanner and anatomy related bias fields in MR imaging. Previously proposed retrospective bias field correction methods suffer from undesired noise amplification that can reduce the quality of bias-corrected DW-MR image. Here, we propose a unified data reconstruction approach that enables joint compensation of bias field as well as data noise in DW-MR imaging. The proposed noise-compensated, bias-corrected (NCBC) data reconstruction method takes advantage of a novel stochastically fully connected joint conditional random field (SFC-JCRF) model to mitigate the effects of data noise and bias field in the reconstructed MR data. The proposed NCBC reconstruction method was tested on synthetic DW-MR data, physical DW-phantom as well as real DW-MR data all acquired using endorectal MR coil. Both qualitative and quantitative analysis illustrated that the proposed NCBC method can achieve improved image quality when compared to other tested bias correction methods. As such, the proposed NCBC method may have potential as a useful retrospective approach for improving the consistency of image interpretations. PMID- 27392348 TI - Activation of Mechanosensitive Transcription Factors in Murine C2C12 Mesenchymal Precursors by Focused Low-Intensity Pulsed Ultrasound (FLIPUS). AB - In this paper, we investigated the mechanoresponse of C2C12 mesenchymal precursor cells to focused low-intensity pulsed ultrasound (FLIPUS). The setup has been developed for in vitro stimulation of adherent cells in the defocused far field of the ultrasound propagating through the bottom of the well plate. Twenty-four well tissue culture plates, carrying the cell monolayers, were incubated in a temperature-controlled water tank. The ultrasound was applied at 3.6-MHz frequency, pulsed at 100-Hz repetition frequency with a 27.8% duty cycle, and calibrated at an output intensity of ISATA = 44.5 +/-7.1 mW/cm2. Numerical sound propagation simulations showed no generation of standing waves in the well plate. The response of murine C2C12 cells to FLIPUS was evaluated by measuring activation of mechanosensitive transcription factors, i.e., activator protein-1 (AP-1), specificity protein 1 (Sp1), and transcriptional enhancer factor (TEAD), and expression of mechanosensitive genes, i.e., c-fos, c-jun, heparin binding growth associated molecule (HB-GAM), and Cyr-61. FLIPUS induced 50% ( p <= 0.05 ) and 70% ( p <= 0.05 ) increases in AP-1 and TEAD promoter activities, respectively, when stimulated for 5 min. The Sp1 activity was enhanced by about 20% ( p <= 0.05 ) after 5-min FLIPUS exposure and the trend persisted for 30-min ( p <= 0.05 ) and 1-h ( p <= 0.05 ) stimulation times. Expressions of mechanosensitive genes c-fos ( p <= 0.05 ), c-jun ( p <= 0.05 ), HB-GAM ( p <= 0.05 ), and cystein-rich protein 61 ( p <= 0.05 ) were enhanced in response to 5 min FLIPUS stimulation. The increase in proliferation of C2C12s occurred after the FLIPUS stimulation ( p <= 0.05 ), with AP-1, Sp1, and TEAD possibly regulating the observed cellular activities. PMID- 27392349 TI - In Vivo Characterization of Cortical Bone Using Guided Waves Measured by Axial Transmission. AB - Cortical bone loss is not fully assessed by the current X-ray methods, and there is an unmet need in identifying women at risk of osteoporotic fracture, who should receive a treatment. The last decade has seen the emergence of the ultrasound (US) axial transmission (AT) techniques to assess a cortical bone. Recent AT techniques exploit the multimode waveguide response of the long bones such as the radius. A recent ex vivo study by our group evidenced that a multimode AT approach can yield simultaneous estimates of cortical thickness (Ct.Th) and stiffness. The aim of this paper is to move one step forward to evaluate the feasibility of measuring multimode guided waves (GW) in vivo and to infer from it cortical thickness. Measurements were taken on the forearm of 14 healthy subjects with the goal to test the accuracy of the estimated thickness using the bidirectional AT method implemented on a dedicated 1-MHz linear US array. This setup allows determining in vivo the dispersion curves of GW transmitted in the cortical layer of the radius. An inverse procedure based on the comparison between the measured and modeled dispersion curves predicted by a 2-D transverse isotropic free plate waveguide model allowed an estimation of cortical thickness, despite the presence of soft tissue. The Ct.Th values were validated by comparison with the site-matched estimates derived from X-ray high resolution peripheral quantitative computed tomography. Results showed a significant correlation between both measurements ( r2 = 0.7 , , and [Formula: see text] mm). This pilot study demonstrates the potential of bidirectional AT for the in vivo assessment of cortical thickness, a bone strength-related factor. PMID- 27392351 TI - Self and Mutual Radiation Impedances for Modeling of Multi-Frequency CMUT Arrays. AB - Multi-frequency capacitive micromachined ultrasonic transducers (CMUTs) consist of interlaced large and small membranes for multiband operation. In modeling these devices, accurate and computationally efficient methods are required for computing self- and mutual-acoustic-radiation impedances. However, most previous works considered mutual-acoustic impedance between radiators of identical size. A need was thus found to revisit the fundamental framework for mutual-acoustic impedance for its applicability to radiators, especially flexural disks, of differing size. The Bouwkamp integral method is used to achieve infinite series expressions for self- and mutual-acoustic radiation impedances. Polynomial fitting-based approximate relations of the mutual-acoustic impedance are developed for arbitrary array geometries and are in good agreement with exact expressions. The derived mutual-acoustic impedance is incorporated into equivalent circuit models of multi-frequency CMUTs showing excellent agreement with finite element modeling. The results demonstrate that mutual-acoustic interactions significantly impact device performance. The framework presented here may prove valuable for future design of multi-frequency arrays for novel multiscale imaging, superharmonic contrast imaging, and image therapy applications. PMID- 27392352 TI - Multiple Kernel Sparse Representation-Based Orthogonal Discriminative Projection and Its Cost-Sensitive Extension. AB - Sparse representation-based classification (SRC) has been developed and shown great potential for real-world application. Based on SRC, Yang et al. devised an SRC steered discriminative projection (SRC-DP) method. However, as a linear algorithm, SRC-DP cannot handle the data with highly nonlinear distribution. Kernel sparse representation-based classifier (KSRC) is a non-linear extension of SRC and can remedy the drawback of SRC. KSRC requires the use of a predetermined kernel function and selection of the kernel function and its parameters is difficult. Recently, multiple kernel learning for SRC (MKL-SRC) has been proposed to learn a kernel from a set of base kernels. However, MKL-SRC only considers the within-class reconstruction residual while ignoring the between-class relationship, when learning the kernel weights. In this paper, we propose a novel multiple kernel sparse representation-based classifier, and then we use it as a criterion to design a multiple kernel sparse representation-based orthogonal discriminative projection method. The proposed algorithm aims at learning a projection matrix and a corresponding kernel from the given base kernels such that in the low dimension subspace the between-class reconstruction residual is maximized and the within-class reconstruction residual is minimized. Furthermore, to achieve a minimum overall loss by performing recognition in the learned low dimensional subspace, we introduce cost information into the dimensionality reduction method. The solutions for the proposed method can be efficiently found based on trace ratio optimization method. Extensive experimental results demonstrate the superiority of the proposed algorithm when compared with the state-of-the-art methods. PMID- 27392353 TI - Separation Surfaces in the Spectral TV Domain for Texture Decomposition. AB - In this paper, we introduce a novel notion of separation surfaces for image decomposition. A surface is embedded in the spectral total-variation (TV) 3D domain and encodes a spatially varying separation scale. The method allows good separation of textures with gradually varying pattern size, pattern contrast, or illumination. The recently proposed TV spectral framework is used to decompose the image into a continuum of textural scales. A desired texture, within a scale range, is found by fitting a surface to the local maximal responses in the spectral domain. A band above and below the surface, referred to as the texture stratum, defines for each pixel the adaptive scale range of the texture. Based on the decomposition, an application is proposed, which can attenuate or enhance textures in the image in a very natural and visually convincing manner. PMID- 27392354 TI - Feature Quality-Based Dynamic Feature Selection for Improving Salient Object Detection. AB - Salient object detection is typically accomplished by combining the outputs of multiple primitive feature detectors (that output feature maps or features). The diversity of images means that different basic features are useful in different contexts, which motivates the use of complementary feature detectors in a general setting. However, naive inclusion of features that are not useful for a particular image leads to a reduction in performance. In this paper, we introduce four novel measures of feature quality and then use those measures to dynamically select useful features for the combination process. The resulting saliency is thereby individually tailored to each image. Using benchmark data sets, we demonstrate the efficacy of our dynamic feature selection system by measuring the performance enhancement over the state-of-the-art models for complementary feature selection and saliency aggregation tasks. We show that a salient object detection technique using our approach outperforms competitive models on the PASCAL VOC 2012 dataset. We find that the most pronounced performance improvements occur in challenging images with cluttered backgrounds, or containing multiple salient objects. PMID- 27392355 TI - Low-Rank Decomposition-Based Restoration of Compressed Images via Adaptive Noise Estimation. AB - Images coded at low bit rates in real-world applications usually suffer from significant compression noise, which significantly degrades the visual quality. Traditional denoising methods are not suitable for the content-dependent compression noise, which usually assume that noise is independent and with identical distribution. In this paper, we propose a unified framework of content adaptive estimation and reduction for compression noise via low-rank decomposition of similar image patches. We first formulate the framework of compression noise reduction based upon low-rank decomposition. Compression noises are removed by soft thresholding the singular values in singular value decomposition of every group of similar image patches. For each group of similar patches, the thresholds are adaptively determined according to compression noise levels and singular values. We analyze the relationship of image statistical characteristics in spatial and transform domains, and estimate compression noise level for every group of similar patches from statistics in both domains jointly with quantization steps. Finally, quantization constraint is applied to estimated images to avoid over-smoothing. Extensive experimental results show that the proposed method not only improves the quality of compressed images obviously for post-processing, but are also helpful for computer vision tasks as a pre processing method. PMID- 27392356 TI - Masking Strategies for Image Manifolds. AB - We consider the problem of selecting an optimal mask for an image manifold, i.e., choosing a subset of the pixels of the image that preserves the manifold's geometric structure present in the original data. Such masking implements a form of compressive sensing through emerging imaging sensor platforms for which the power expense grows with the number of pixels acquired. Our goal is for the manifold learned from masked images to resemble its full image counterpart as closely as possible. More precisely, we show that one can indeed accurately learn an image manifold without having to consider a large majority of the image pixels. In doing so, we consider two masking methods that preserve the local and global geometric structure of the manifold, respectively. In each case, the process of finding the optimal masking pattern can be cast as a binary integer program, which is computationally expensive but can be approximated by a fast greedy algorithm. Numerical experiments show that the relevant manifold structure is preserved through the data-dependent masking process, even for modest mask sizes. PMID- 27392358 TI - Generalized Pooling for Robust Object Tracking. AB - Feature pooling in a majority of sparse coding-based tracking algorithms computes final feature vectors only by low-order statistics or extreme responses of sparse codes. The high-order statistics and the correlations between responses to different dictionary items are neglected. We present a more generalized feature pooling method for visual tracking by utilizing the probabilistic function to model the statistical distribution of sparse codes. Since immediate matching between two distributions usually requires high computational costs, we introduce the Fisher vector to derive a more compact and discriminative representation for sparse codes of the visual target. We encode target patches by local coordinate coding, utilize Gaussian mixture model to compute Fisher vectors, and finally train semi-supervised linear kernel classifiers for visual tracking. In order to handle the drifting problem during the tracking process, these classifiers are updated online with current tracking results. The experimental results on two challenging tracking benchmarks demonstrate that the proposed approach achieves a better performance than the state-of-the-art tracking algorithms. PMID- 27392357 TI - Multi-Tissue Decomposition of Diffusion MRI Signals via Sparse-Group Estimation. AB - Sparse estimation techniques are widely utilized in diffusion magnetic resonance imaging (DMRI). In this paper, we present an algorithm for solving the l0 sparse group estimation problem and apply it to the tissue signal separation problem in DMRI. Our algorithm solves the l0 problem directly, unlike existing approaches that often seek to solve its relaxed approximations. We include the mathematical proofs showing that the algorithm will converge to a solution satisfying the firstorder optimality condition within a finite number of iterations. We apply this algorithm to DMRI data to tease apart signal contributions from white matter, gray matter, and cerebrospinal fluid with the aim of improving the estimation of the fiber orientation distribution function (FODF). Unlike spherical deconvolution approaches that assume an invariant fiber response function (RF), our approach utilizes an RF group to span the signal subspace of each tissue type, allowing greater flexibility in accounting for possible variations of the RF throughout space and within each voxel. Our l0 algorithm allows for the natural groupings of the RFs to be considered during signal decomposition. Experimental results confirm that our method yields estimates of FODFs and volume fractions of tissue compartments with improved robustness and accuracy. Our l0 algorithm is general and can be applied to sparse estimation problems beyond the scope of this paper. PMID- 27392359 TI - Deep and Structured Robust Information Theoretic Learning for Image Analysis. AB - This paper presents a robust information theoretic (RIT) model to reduce the uncertainties, i.e., missing and noisy labels, in general discriminative data representation tasks. The fundamental pursuit of our model is to simultaneously learn a transformation function and a discriminative classifier that maximize the mutual information of data and their labels in the latent space. In this general paradigm, we, respectively, discuss three types of the RIT implementations with linear subspace embedding, deep transformation, and structured sparse learning. In practice, the RIT and deep RIT are exploited to solve the image categorization task whose performances will be verified on various benchmark data sets. The structured sparse RIT is further applied to a medical image analysis task for brain magnetic resonance image segmentation that allows group-level feature selections on the brain tissues. PMID- 27392360 TI - Double Low Rank Matrix Recovery for Saliency Fusion. AB - In this paper, we address the problem of fusing various saliency detection methods such that the fusion result outperforms each of the individual methods. We observe that the saliency regions shown in different saliency maps are with high probability covering parts of the salient object. With image regions being represented by the saliency values of multiple saliency maps, the object regions have strong correlation and thus lie in a low-dimensional subspace. Meanwhile, most of background regions tend to have lower saliency values in various saliency maps. They are also strongly correlated and lie in a lowdimensional subspace that is independent of the object subspace. Therefore, an image can be represented as the combination of two low rank matrices. To obtain a unified low rank matrix that represents the salient object, this paper presents a double low rank matrix recovery model for saliency fusion. The inference process is formulated as a constrained nuclear norm minimization problem, which is convex and can be solved efficiently with the alternating direction method of multipliers (ADMM). Furthermore, to reduce the computational complexity of the proposed saliency fusion method, a saliency model selection strategy based on the sparse representation is proposed. Experiments on five datasets show that our method consistently outperforms each individual saliency detection approach and other state-of-the-art saliency fusion methods. PMID- 27392361 TI - Motor Imagery Classification Based on Bilinear Sub-Manifold Learning of Symmetric Positive-Definite Matrices. AB - In motor imagery brain-computer interfaces (BCIs), the symmetric positive definite (SPD) covariance matrices of electroencephalogram (EEG) signals carry important discriminative information. In this paper, we intend to classify motor imagery EEG signals by exploiting the fact that the space of SPD matrices endowed with Riemannian distance is a high-dimensional Riemannian manifold. To alleviate the overfitting and heavy computation problems associated with conventional classification methods on high-dimensional manifold, we propose a framework for intrinsic sub-manifold learning from a high-dimensional Riemannian manifold. Considering a special case of SPD space, a simple yet efficient bilinear sub manifold learning (BSML) algorithm is derived to learn the intrinsic sub-manifold by identifying a bilinear mapping that maximizes the preservation of the local geometry and global structure of the original manifold. Two BSML-based classification algorithms are further proposed to classify the data on a learned intrinsic sub-manifold. Experimental evaluation of the classification of EEG revealed that the BSML method extracts the intrinsic sub-manifold approximately 5* faster and with higher classification accuracy compared with competing algorithms. The BSML also exhibited strong robustness against a small training dataset, which often occurs in BCI studies. PMID- 27392364 TI - Strategies for Comparing Metabolic Profiles: Implications for the Inference of Biochemical Mechanisms from Metabolomics Data. AB - BACKGROUND: Large amounts of metabolomics data have been accumulated in recent years and await analysis. Previously, we had developed a systems biology approach to infer biochemical mechanisms underlying metabolic alterations observed in cancers and other diseases. The method utilized the typical Euclidean distance for comparing metabolic profiles. Here, we ask whether any of the numerous alternative metrics might serve this purpose better. METHODS AND FINDINGS: We used enzymatic alterations in purine metabolism that were measured in human renal cell carcinoma to test various metrics with the goal of identifying the best metrics for discerning metabolic profiles of healthy and diseased individuals. The results showed that several metrics have similarly good performance, but that some are unsuited for comparisons of metabolic profiles. Furthermore, the results suggest that relative changes in metabolite levels, which reduce bias toward large metabolite concentrations, are better suited for comparisons of metabolic profiles than absolute changes. Finally, we demonstrate that a sequential search for enzymatic alterations, ranked by importance, is not always valid. CONCLUSIONS: We identified metrics that are appropriate for comparisons of metabolic profiles. In addition, we constructed strategic guidelines for the algorithmic identification of biochemical mechanisms from metabolomics data. PMID- 27392365 TI - Predicting microRNA-disease associations based on improved microRNA and disease similarities. AB - MicroRNAs (miRNAs) are a type of non-coding RNAs with about ~22nt nucleotides. Increasing evidences have shown that miRNAs play critical roles in many human diseases. The identification of human disease-related miRNAs is helpful to explore the underlying pathogenesis of diseases. More and more experimental validated associations between miRNAs and diseases have been reported in the recent studies, which provide useful information for new miRNA-disease association discovery. In this study, we propose a computational framework, KBMF MDI, to predict the associations between miRNAs and diseases based on their similarities. The sequence and function information of miRNAs are used to measure similarity among miRNAs while the semantic and function information of disease are used to measure similarity among diseases, respectively. In addition, the kernelized Bayesian matrix factorization method is employed to infer potential miRNA-disease associations by integrating these data sources. We applied this method to 6084 known miRNA-disease associations and utilized 5-fold cross validation to evaluate the performance. The experimental results demonstrate that our method can effectively predict unknown miRNA-disease associations. PMID- 27392366 TI - Active Manual Movement Improves Directional Perception of Illusory Force. AB - Active touch sensing is known to facilitate the discrimination or recognition of the spatial properties of an object from the movement of tactile sensors on the skin and by integrating proprioceptive feedback about hand positions or motor commands related to ongoing hand movements. On the other hand, several studies have reported that tactile processing is suppressed by hand movement. Thus, it is unclear whether or not the active exploration of force direction by using hand or arm movement improves the perception of the force direction. Here, we show that active manual movement in both the rotational and translational directions enhances the precise perception of the force direction. To make it possible to move a hand in space without any physical constraints, we have adopted a method of inducing the sensation of illusory force by asymmetric vibration. We found that the precision of the perceived force direction was significantly better when the shoulder is rotated medially and laterally. We also found that directional errors supplied by the motor response of the perceived force were smaller than those resulting from perceptual judgments between visual and haptic directional stimuli. These results demonstrate that active manual movement boosts the precision of the perceived direction of an illusory force. PMID- 27392367 TI - Distributed Event-Based Set-Membership Filtering for a Class of Nonlinear Systems With Sensor Saturations Over Sensor Networks. AB - In this paper, the distributed set-membership filtering problem is investigated for a class of discrete time-varying system with an event-based communication mechanism over sensor networks. The system under consideration is subject to sector-bounded nonlinearity, unknown but bounded noises and sensor saturations. Each intelligent sensing node transmits the data to its neighbors only when certain triggering condition is violated. By means of a set of recursive matrix inequalities, sufficient conditions are derived for the existence of the desired distributed event-based filter which is capable of confining the system state in certain ellipsoidal regions centered at the estimates. Within the established theoretical framework, two additional optimization problems are formulated: one is to seek the minimal ellipsoids (in the sense of matrix trace) for the best filtering performance, and the other is to maximize the triggering threshold so as to reduce the triggering frequency with satisfactory filtering performance. A numerically attractive chaos algorithm is employed to solve the optimization problems. Finally, an illustrative example is presented to demonstrate the effectiveness and applicability of the proposed algorithm. PMID- 27392368 TI - Dissipativity-Based Reliable Control for Fuzzy Markov Jump Systems With Actuator Faults. AB - This paper is concerned with the problem of reliable dissipative control for Takagi-Sugeno fuzzy systems with Markov jumping parameters. Considering the influence of actuator faults, a sufficient condition is developed to ensure that the resultant closed-loop system is stochastically stable and strictly ( Q, S,R ) dissipative based on a relaxed approach in which mode-dependent and fuzzy-basis dependent Lyapunov functions are employed. Then a reliable dissipative control for fuzzy Markov jump systems is designed, with sufficient condition proposed for the existence of guaranteed stability and dissipativity controller. The effectiveness and potential of the obtained design method is verified by two simulation examples. PMID- 27392369 TI - Working Title: Special Issue on Youth Energy Expenditure. AB - No abstract available for this article. PMID- 27392370 TI - Energy Cost of Activities in Preschool-Aged Children. AB - BACKGROUND: The absolute energy cost of activities in children increase with age due to greater muscle mass and physical capability associated with growth and developmental maturation; however, there is a paucity of data in preschool-aged children. Study aims were 1) to describe absolute and relative energy cost of common activities of preschool-aged children in terms of VO2, energy expenditure (kilocalories per minute) and child-specific metabolic equivalents (METs) measured by room calorimetry for use in the Youth Compendium of Physical Activity, and 2) to predict METs from age, sex and heart rate (HR). METHODS: Energy expenditure (EE), oxygen consumption (VO2), HR, and child-METs of 13 structured activities were measured by room respiration calorimetry in 119 healthy children, ages 3 to 5 years. RESULTS: EE, VO2, HR, and child-METs are presented for 13 structured activities ranging from sleeping, sedentary, low-, moderate- to high-active. A significant curvilinear relationship was observed between child-METs and HR (r2 = .85; P = .001). CONCLUSION: Age-specific child METs for 13 structured activities in preschool-aged children will be useful to extend the Youth Compendium of Physical Activity for research purposes and practical applications. HR may serve as an objective measure of MET intensity in preschool-aged children. PMID- 27392371 TI - Energy Expenditure of Common Sedentary Activities in Youth. AB - BACKGROUND: Standardized measures of energy expenditure (EE) for sedentary activities in youth are needed. The goal was to determine EE of common contemporary and computer-related sedentary activities in youth. METHODS: We measured EE for sedentary tasks in 10- to 17-year-old youths (n = 24) during ~24 hours in a whole-room indirect calorimeter. Directly monitored tasks were performed for ~10-min. EE was calculated from oxygen consumed and carbon dioxide produced, converted to metabolic equivalents (MET) by normalization to an individual's measured resting EE, and compared with the Compendium of Energy Expenditures for Youth. RESULTS: Compared with the youth compendium, measured METs were lower for internet surfing (1.3), computer keyboard typing (1.3), and sorting beads/crafts (1.5) (all P < .002), and similar for handwriting (1.4), playing cards (1.6), video-gaming (1.6), and telephoning (1.5). CONCLUSIONS: Current youth compendium MET estimates should be used with caution when predicting EE of common contemporary and computer-related sedentary activities in youth. PMID- 27392372 TI - Comparison of Energy Expenditure of Youth Playing Tennis During Practice and Match Settings. AB - BACKGROUND: Researchers have investigated the energy expenditure of tennis practice and match play in adults but not youth. METHODS: VO2 was recorded for 36 youth, ages 9 to 18, during 10-minute bouts of tennis practice and match play. A GLM was used to compare VO2 between practice and match play and among age groups (9-12 years, 13-15 years, and 16-18 years); also to compare the difference in adult and child-derived MET values (DeltaMET). RESULTS: VO2 was higher for tennis match play vs. practice (P < .05) and there was a trend for 16 to 18 year olds having lower VO2 than 9 to 12 year olds (P = .055). DeltaMET did not differ between settings but varied by age group (P = .004); it was highest in 9- to 12 year-olds and lowest in 16- to 18-year-olds. CONCLUSIONS: Youth expend more energy while playing a tennis match than practice, regardless of age. Child derived MET values equaled those of adults once youth reached ages 16 to 18. PMID- 27392373 TI - Energy Expenditure for 70 Activities in Children and Adolescents. AB - BACKGROUND: Thirty-five percent of the activities assigned MET values in the Compendium of Energy Expenditures for Youth were obtained from direct measurement of energy expenditure (EE). The aim of this study was to provide directly measured EE for several different activities in youth. METHODS: Resting metabolic rate (RMR) of 178 youths (80 females, 98 males) was first measured. Participants then performed structured activity bouts while wearing a portable metabolic system to directly measure EE. Steady-state oxygen consumption data were used to compute activity METstandard (activity VO2/3.5) and METmeasured (activity VO2/measured RMR) for the different activities. RESULTS: Rates of EE were measured for 70 different activities and ranged from 1.9 to 12.0 METstandard and 1.5 to 10.0 METmeasured. CONCLUSION: This study provides directly measured energy cost values for 70 activities in children and adolescents. It contributes empirical data to support the expansion of the Compendium of Energy Expenditures for Youth. PMID- 27392374 TI - Youth Energy Expenditure During Common Free-Living Activities and Treadmill Walking. AB - BACKGROUND: Energy expenditure (EE) estimates for a broad age range of youth performing a variety of activities are needed. METHODS: 106 participants (6-18 years) completed 6 free-living activities (seated rest, movie watching, coloring, stair climbing, basketball dribbling, jumping jacks) and up to 9 treadmill walking bouts (13.4 to 120.7 m/min; 13.4 m/min increments). Breath-by-breath oxygen uptake (VO2) was measured using the COSMED K4b2 and EE was quantified as youth metabolic equivalents (METy1:VO2/measured resting VO2, METy2:VO2/estimated resting VO2). Age trends were evaluated with ANOVA. RESULTS: Seated movie watching produced the lowest mean METy1 (6- to 9-year-olds: 0.94 +/- 0.13) and METy2 values (13- to 15-year-olds: 1.10 +/- 0.19), and jumping jacks produced the highest mean METy1 (13- to 15-year-olds: 6.89 +/- 1.47) and METy2 values (16- to 18-year-olds: 8.61 +/- 2.03). Significant age-related variability in METy1 and METy2 were noted for 8 and 2 of the 15 evaluated activities, respectively. CONCLUSIONS: Descriptive EE data presented herein will augment the Youth Compendium of Physical Activities. PMID- 27392375 TI - Energy Expenditure of Daily Living Activities in 3- to 6-Year-Old Children. AB - BACKGROUND: There has been a call for updating the Youth Compendium of Energy Expenditure (YCEE) by including energy expenditure (EE) data of young children (ie, < 6-year-old children). Therefore, this study examined the activity EE in 3 to 6 year old children using indirect calorimetry. METHODS: Using Oxycon Mobile portable indirect calorimetry, both the oxygen consumption (VO2) and the EE of 28 children (Girls: 46%, Age: 4.8 +/- 1.0, BMI: 16.4 +/- 1.6) were measured while they performed various daily living activities (eg, watching TV, playing with toys, shooting baskets, soccer). RESULTS: Across physical activities, averages of VO2 (ml.kg.min-1), VO2 (L.min-1), and EE ranged from 8.9 +/- 1.5 to 33.3 +/- 4.8 ml.kg.min-1, from 0.17 +/- 0.04 to 0.64 +/- 0.16 L.min-1, and from 0.8 +/- 0.2 to 3.2 +/- 0.7 kcal.min-1, respectively. CONCLUSIONS: These findings will contribute to the upcoming YCEE update. PMID- 27392376 TI - Developmental Trends in the Energy Cost of Physical Activities Performed by Youth. AB - BACKGROUND: Published energy cost data for children and adolescents are lacking. The purpose of this study was to measure and describe developmental trends in the energy cost of 12 physical activities commonly performed by youth. METHODS: A mixed age cohort of 209 participants completed 12 standardized activity trials on 4 occasions over a 3-year period (baseline, 12-months, 24-months, and 36-months) while wearing a portable indirect calorimeter. Bayesian hierarchical regression was used to link growth curves from each age cohort into a single curve describing developmental trends in energy cost from age 6 to 18 years. RESULTS: For sedentary and light-intensity household chores, YOUTH METs (METy) remained stable or declined with age. In contrast, METy values associated with brisk walking, running, basketball, and dance increased with age. CONCLUSIONS: The reported energy costs for specific activities will contribute to efforts to update and expand the youth compendium. PMID- 27392377 TI - Examining Energy Expenditure in Youth Using XBOX Kinect: Differences by Player Mode. AB - BACKGROUND: Replacing sedentary time with physical activity through new generation exergames (eg, XBOX Kinect) is a potential intervention strategy. The study's purpose was to compare youth energy expenditure while playing different exergames in single- vs. multiplayer mode. METHODS: Participants (26 male, 14 female) were 10 to 13 years old. They wore a portable metabolic analyzer while playing 4 XBOX Kinect games for 15 minutes each (2 single-, 2 multiplayer). Repeated-measures ANOVA (with Bonferroni correction) was used to examine player mode differences, controlling for age group, sex, weight status, and game. RESULTS: There was a significant difference in energy expenditure between single player (mean = 15.4 ml/kg/min, SD = 4.5) and multiplayer mode (mean = 16.8 ml/kg/min, SD = 4.7). Overweight and obese participants (mean = 13.7 ml/kg/min, SD = 4.2) expended less energy than normal weight (mean = 17.8 ml/kg/min, SD = 4.5) during multiplayer mode (d = 0.93). CONCLUSION: Player mode, along with personal factors such as weight status, may be important to consider in energy expenditure during exergames. PMID- 27392378 TI - Energy Cost of Children's Structured and Unstructured Games. AB - BACKGROUND: Limited data are available on energy cost of common children's games using measured oxygen consumption. METHODS: Children (10.6 +/- 2.9 years; N = 37; 26 male, 9 female) performed a selection of structured (bowling, juggling, obstacle course, relays, active kickball) and unstructured (basketball, catch, tennis, clothespin tag, soccer) activities for 5 to 30 minutes. Resting metabolic rate (RMR) was calculated using Schofield's age- and sex-specific equation. Children wore a portable metabolic unit, which measured expired gases to obtain oxygen consumption (VO2), youth METs (relative VO2/child's calculated RMR), and activity energy expenditure (kcal/kg/min). Descriptive statistics were used to summarize data. RESULTS: Relative VO2 ranged from 16.8 +/- 4.6 ml/kg/min (bowling) to 32.2 +/- 6.8 ml/kg/min (obstacle course). Obstacle course, relays, active kickball, soccer, and clothespin tag elicited vigorous intensity (>6 METs), the remainder elicited moderate intensity (3-6 METs). CONCLUSIONS: This article contributes energy expenditure data for the update and expansion of the youth compendium. PMID- 27392379 TI - Metabolic Equivalents of Selected Sedentary and Physical Activities in Chinese Youth. AB - BACKGROUND: This study determined the metabolic equivalents (METs) of several activities typically performed by Chinese youth. METHODS: Thirty youth (12 years) performed 7 activities that reflected their daily activities while Energy Expenditure (EE) was measured in a metabolic chamber. RESULTS: METs were calculated as activity EE divided by participant's measured resting metabolic rate. A MET value ranging from 0.8 to 1.2 was obtained for sleeping, watching TV, playing computer games, reading and doing homework. Performing radio gymnastics had a MET value of 2.9. Jumping rope at low effort required 3.1 METs. Except for watching TV, METs for other activities in this study were lower than Youth Compendium values. CONCLUSIONS: The results provide empirical evidence for more accurately assessing EE of activities commonly performed by Chinese youth. This is the first study to determine METs for radio gymnastics and jump rope in Chinese youth. PMID- 27392381 TI - The Energy Expenditure of Free-Living Physical Activities in Primary Schoolchildren. AB - BACKGROUND: The aim of this study is to establish the energy expenditure (EE) of a range of child-relevant activities and to compare different methods of estimating activity MET. METHODS: 27 children (17 boys) aged 9 to 11 years participated. Participants were randomly assigned to 1 of 2 routines of 6 activities ranging from sedentary to vigorous intensity. Indirect calorimetry was used to estimate resting and physical activity EE. Activity metabolic equivalent (MET) was determined using individual resting metabolic rate (RMR), the Harrell MET and the Schofield equation. RESULTS: Activity EE ranges from 123.7+/- 35.7 J/min/Kg (playing cards) to 823.1 +/- 177.8 J/min/kg (basketball). Individual RMR, the Harrell-MET and the Schofield equation MET prediction were relatively similar at light and moderate but not at vigorous intensity. Schofield equation provided a better comparison with the Compendium of Energy Expenditure for Youth. CONCLUSION: This information might be advantageous to support the development of a new Compendium of Energy Expenditure for Youth. PMID- 27392380 TI - Energy Expenditure and Intensity of Classroom Physical Activity in Elementary School Children. AB - BACKGROUND: There is limited data regarding objectively measured energy cost and intensity of classroom instruction. Therefore, the purpose of current study was to objectively measure energy cost and subsequently calculate MET values using a portable indirect calorimeter (IC) for both normal classroom instruction (NCI) and active classroom instruction (ACI). METHODS: We assessed energy expenditure (EE) and intensity levels (METs) in elementary school children (17 boys and 15 girls) using an IC (COSMED K4b2). Independent t-tests were used to evaluate potential sex and grade level differences for age, BMI, VO2, EE, and METs. RESULTS: The average EE for NCI and ACI were 1.8 +/- 0.4 and 3.9 +/- 1.0, respectively. The average intensity level for NCI and ACI were 1.9 +/- 0.4 and 4.2 +/- 0.9 METs, respectively. CONCLUSIONS: PA delivered through ACI can elicit EE at a moderate intensity level. These results provide evidence for ACI as a convenient/feasible avenue for increasing PA in youth without decreasing instruction time. PMID- 27392382 TI - Activity Energy Expenditure in Youth: Sex, Age, and Body Size Patterns. AB - BACKGROUND: The assessment of physical activity (PA) and energy expenditure (EE) in youth is complicated by inherent variability in growth and maturation during childhood and adolescence. This study provides descriptive summaries of the EE of a diverse range of activities in children ages 7 to 13. METHODS: A sample of 105 7- to 13-year-old children (boys: 57%, girls: 43%, and Age: 9.9 +/- 1.9) performed a series of 12 activities from a pool of 24 activities while being monitored with an indirect calorimetry system. RESULTS: Across physical activities, averages of VO2 ml.kg.min-1, VO2 L.min-1, EE, and METs ranged from 3.3 to 53.7 ml.kg.min-1, from 0.15 to 3.2 L.min-1, from 0.7 to 15.9 kcal.min-1, 1.5 MET to 7.8 MET, respectively. CONCLUSIONS: The energy costs of the activities varied by age, sex, and BMI status reinforcing the need to consider adjustments when examining the relative intensity of PA in youth. PMID- 27392383 TI - Energy Cost of Physical Activities and Sedentary Behaviors in Young Children. AB - BACKGROUND: This study reports energy expenditure (EE) data for lifestyle and ambulatory activities in young children. METHODS: Eleven children aged 3 to 6 years (mean age = 4.8 +/- 0.9; 55% boys) completed 12 semistructured activities including sedentary behaviors (SB), light (LPA), and moderate-to-vigorous physical activities (MVPA) over 2 laboratory visits while wearing a portable metabolic system to measure EE. RESULTS: Mean EE values for SB (TV, reading, tablet and toy play) were between 0.9 to 1.1 kcal/min. Standing art had an energy cost that was 1.5 times that of SB (mean = 1.4 kcal/min), whereas bike riding (mean = 2.5 kcal/min) was similar to LPA (cleaning-up, treasure hunt and walking) (mean = 2.3 to 2.5 kcal/min), which had EE that were 2.5 times SB. EE for MVPA (running, active games and obstacle course) was 4.2 times SB (mean = 3.8 to 3.9 kcal/min). CONCLUSION: EE values reported in this study can contribute to the limited available data on the energy cost of lifestyle and ambulatory activities in young children. PMID- 27392384 TI - Energy Cost of Free-Play Activities in 10- to 11-Year-Old Children. AB - OBJECTIVE: This study sought to ascertain the energy expenditure (EE) associated with different sedentary and physically active free-play activities in primary school-aged children. METHODS: Twenty-eight children (13 boys; 11.4 +/- 0.3 years; 1.45 +/- 0.09 m; 20.0 +/- 4.7 kg?m-2) from 1 primary school in Northwest England engaged in 6 activities representative of children's play for 10 minutes (drawing, watching a DVD, playground games and free-choice) and 5 minutes (self paced walking and jogging), with 5 minutes rest between each activity. Gas exchange variables were measured throughout. Resting energy expenditure was measured during 15 minutes of supine rest. RESULTS: Child (Schofield-predicted) MET values for watching a DVD, self-paced jogging and playing reaction ball were significantly higher for girls (P < .05). CONCLUSION: Utilizing a field-based protocol to examine children's free-living behaviors, these data contribute to the scarcity of information concerning children's EE during play to update the Compendium of Energy Expenditures for Youth. PMID- 27392385 TI - The Energy Cost of Household Chores, Rollerblading, and Riding Scooters in 9- to 14-Year-Old Children. AB - BACKGROUND: To improve the scope of the Youth Compendium of Energy Expenditures, a range of everyday activities of varying intensity should be measured. This study measures the energy cost of children undertaking common household chores, rollerblading and riding a foot-propelled scooter. METHODS: Participants were 9- to 14-year-old children. A metabolic cart was used to measure oxygen cost (VO2) of a variety of household chores. A Cosmed K4b2 portable oxygen analyzer was used to measure VO2 during rollerblading and riding a scooter at self-selected speeds. Energy costs for each participant were calculated as child METs. RESULTS: Mean child MET costs for the household chores ranged from 1.3 to 3.6 METs. Rollerblading and riding a scooter yielded mean child MET costs of 6.5 and 6.3 METs respectively. CONCLUSIONS: Household chores were found to be of light to moderate intensity, while rollerblading and riding a scooter were vigorous activities. PMID- 27392386 TI - Predictive Validity of a Thigh-Worn Accelerometer METs Algorithm in 5- to 12-Year old Children. AB - BACKGROUND: To validate the activPAL3 algorithm for predicting metabolic equivalents (TAMETs) and classifying MVPA in 5- to 12-year-old children. METHODS: Fifty-seven children (9.2 +/- 2.3y, 49.1% boys) completed 14 activities including sedentary behaviors (SB), light (LPA) and moderate-to-vigorous physical activities (MVPA). Indirect calorimetry (IC) was used as the criterion measure. Analyses included equivalence testing, Bland-Altman procedures and area under the receiver operating curve (ROC-AUC). RESULTS: At the group level, TAMETs were significantly equivalent to IC for handheld e-game, writing/coloring, and standing class activity (P < .05). Overall, TAMETs were overestimated for SB (7.9 +/- 6.7%) and LPA (1.9 +/- 20.2%) and underestimated for MVPA (27.7 +/- 26.6%); however, classification accuracy of MVPA was good (ROC-AUC = 0.86). Limits of agreement were wide for all activities, indicating large individual error (SB: 27.6% to 44.7%; LPA: -47.1% to 51.0%; MVPA: -88.8% to 33.9%). CONCLUSIONS: TAMETs were accurate for some SB and standing, but were overestimated for overall SB and LPA, and underestimated for MVPA. Accuracy for classifying MVPA was, however, acceptable. PMID- 27392387 TI - Adversarial Growth in Olympic Swimmers: Constructive Reality or Illusory Self Deception? AB - Previous research suggests that adversarial growth is a real and constructive phenomenon that occurs in athletes who compete at the highest level of sport. In this study, however, we adopt a critical stance on the veridicality of growth by exploring Olympic swimmers' experience of constructive and illusory growth. Semistructured interviews, complemented by timelining, were analyzed using interpretative phenomenological analysis. Despite the inherently negative aspects of adversity, it was evident from the swimmers' interpretations that they also perceived positive consequences of their experiences. Analysis revealed that some of these positive outcomes were indicative of illusory aspects of growth, and other positive outcomes were more indicative of constructive aspects of growth. It appears that earlier phases of the growth process were characterized by more illusory aspects of growth, whereas when the temporal proximity from the adversity increased, more constructive aspects of growth were apparent. PMID- 27392388 TI - Steroid-Eluting Ethmoidal Stent Versus Antero-Posterior Ethmoidectomy: Comparison Of Efficacy And Safety In Allergic Patients. AB - BACKGROUND: Allergic and chronic rhinosinusitis is a disabling pathological condition with an 8% prevalence in the European population and 5% in the Italian one. The ethmoidal sinus is the first one involved in the inflammation. The typical surgical procedure to manage ethmoidal sinusitis is an endoscopic antero posterior ethmoidectomy. Recently introduced on the European market balloon called Relieva Stratus MicroFlow Spacer can be inserted within the ethmoid, with a local slow release of a steroid drug. This study had the aim to evaluate the efficacy and safety of the steroid-eluting ethmoidal stent in the management of allergic chronic rhinosinusitis in comparison with the traditional endoscopic ethmoidectomy. Methodos: 70 allergic patients who presented chronic rhinosinusitis were randomly divided into 2 groups and receive respectively the steroid-eluting ethmoidal stent or endoscopic ethmoidectomy. RESULTS: The most significant observation coming from the comparative analysis of the results is the substantial equivalence of the treatment with the steroid-eluting ethmoidal stent (SEES) compared with endoscopic ethmoidectomy in the management of ethmoid chronic rhinosinusitis with the exception of a reduction of overall discomfort and nasal secretion and better functional results at rhinomanometry in the steroid-eluting ethmoidal stent group. CONCLUSION: in our experience, the SEES was efficacious in the treatment of allergic patients with ethmoidal CRS when conventional medical treatment had failed, or when wishing to avoid the classic endoscopic ethmoidectomy (EE). However, further long-term studies will be performed in order to confirm the safety and stability, over time, of the results obtained. PMID- 27392389 TI - Operative advancement is a never-ending obligation. PMID- 27392390 TI - Effect of age, patient's sex, and type of trauma on the correlation between size of sphincter defect and anal pressures in posttraumatic fecal incontinence. AB - BACKGROUND: The physiologic assessment of anal sphincters in cases of posttraumatic fecal incontinence is a fundamental step in planning operative treatment. In this study, we evaluate the correlation between size of anal sphincter defect, anal pressures, and clinical symptoms in patients with posttraumatic fecal incontinence. We also investigate the impact of patients' age, sex, and type of trauma on this correlation. METHODS: Records of 70 patients fitting the study's eligibility criteria were collected retrospectively from the archives of Mansoura University Hospitals' colorectal surgery unit. Demographic data of patients, causes of fecal incontinence, images of sphincter defects on endorectal ultrasonography, anal resting and squeeze pressures, and Wexner continence scores were collected, and correlation analysis was performed. RESULTS: Seventy patients (54 males and 16 females) with a mean (+/-standard deviation) age of 36 +/- 16 years were studied. Mean maximal resting anal pressure was 42 +/- 16 mm Hg, and mean maximal squeeze anal pressure was 80 +/- 35 mm Hg. Size of external anal sphincter defect was negatively correlated with mean maximal squeeze (r = -0.4298). Mean Wexner continence score was correlated positively with size of external anal sphincter defect (r = 0.3743). Both correlations became significantly stronger in female patients, patients greater than 50 years, postfistulectomy patients, and patients with obstetric injuries. CONCLUSION: Size of external anal sphincter defect correlates negatively with mean maximal squeeze and positively with symptoms score. This correlation is stronger in females, patients greater than 50 years, and patients with postfistulectomy or obstetric injuries. These findings suggest that this group of patients requires additional assessment before surgical repair. PMID- 27392392 TI - [Not Available]. AB - Authors report a retrospective study of all cases of indoramin-only poisoning notified to the Paris poison Centre from 1986 to 2010. Fifty five cases of indoramin self-poisoning were included: 40 adults and 15 children. The mean supposed ingested dose was about 701mg+/-464mg. ECG showed a prolonged QTc interval (equal to or greater than 0.50s) in 30% of patients. The lowest observed dose for prolonged QTc was 625mg. This series includes two cases of seizures occurring around two hours after ingestion of 900 and 2 250mg of indoramin. A review of the literature showed cardiac disorders, with a delayed mechanism of action up until 18hours after ingestion. Therefore, rapid medical resuscitation and prolonged cardiac monitoring for at least 24hours after ingestion of 625mg are recommended. PMID- 27392391 TI - Incidence of hepaticojejunostomy stricture after hepaticojejunostomy. AB - BACKGROUND: Operations requiring biliary-enteric anastomosis are uncommon, and the true incidence of postoperative stricture is unknown. Our goal was to determine the timing, incidence, and management of stricture after biliary enteric anastomosis. METHODS: We used 5% Medicare claims data (1996-2011) to identify patients >=66 years who underwent an operation requiring a biliary enteric anastomosis. A cumulative incidence curve was used to describe timing of stricture diagnosis. The use of imaging and intervention was evaluated. A Cox proportional hazards model was constructed to identify factors associated with stricture. RESULTS: A total of 3,374 patients underwent an operation requiring either a hepaticojejunostomy (54.33%; N = 1,833) or choledochojejunostomy (45.67%; N = 1,541); 2-year survival was 57.0%. Overall, 403 (11.9%) patients developed a stricture. The cumulative incidence of stricture was 12.5% at 2 years. Mean time to stricture diagnosis was 16.8 +/- 21.6 months (median = 8.5 months); 23% of patients with a stricture required hospitalization for cholangitis (N = 94). Only 18 (4.5%) patients with a stricture required reoperation. Younger age (hazard ratio 0.98; 95% confidence interval 0.98-0.99) was associated with a decreased likelihood of stricture formation; presence of an endostent (hazard ratio 1.66; 95% confidence interval 1.35-2.04) predicted stricture formation. CONCLUSION: Biliary-enteric anastomotic strictures occur with significant frequency after a biliary-enteric anastomosis. Although many patients are managed nonoperatively, stricture diagnosis remains burdensome. PMID- 27392393 TI - Extraction of Water-soluble Soybean Polysaccharides under Acidic Conditions. AB - We investigated the yield, gelation and sugar composition of water-soluble polysaccharides that had been extracted from soybean cotyledons under acidic conditions. SSPS were easily extracted at several pHs. The highest yield was about twice that reported by Morita et al., after extraction in boiling water, or by Kawamura et al., after extraction in hot water (90 degrees C) with the stepwise addition of ammonium oxalate and 0.5% NaOH. Our results show that the average molecular weight was relatively high for both SSPS extracted in the weakly acidic pH range of 4-6 at 100-120 degrees C and in the strongly acidic pH range of 2-3 at 40-80 degrees C. The water-soluble polysaccharide solutions which were extracted under the former conditions remained fluid, but those which were extracted under the latter conditions gelled. However, the molecular weight distribution and sugar composition were similar for SSPS isolated by using both sets of conditions. Furthermore, water-soluble soybean polysaccharides were found to consist of rhamnogalacturonans, which could endure hydrolysis, and arabinogalactans, which were easily hydrolyzed under acidic conditions. PMID- 27392394 TI - Hydroxyl Radical Generation Depending on O2 or H2O by a Photocatalyzed Reaction in an Aqueous Suspension of Titanium Dioxide. AB - Photocatalytic production of the electron (e(-)) and positive hole (h(+)) in an aqueous suspension of TiO2 (anatase form) under illumination by near-UV light (295-390 nm) generated the superoxide (O2 (-)) and hydroxyl radical (*OH), which both proceeded linearly with reaction time, while H2O2 accumulated non-linearly. Under anaerobic conditions (introduced Ar gas), the yields of three active species of oxygen were decreased to 10-20% of those detected in the air-saturated reaction. The electron spin resonance (ESR) signal characteristics of *OH were obtained when a spin trap of 5,5-dimthyl-1-pyrroline-N-oxide (DMPO) was included in the illuminating mixture. The intensity of the ESR signal was increased by Cu/Zn superoxide dismutase, and decreased under anaerobic conditions, amounting to only 20% of the intensity detected in the aerobic reaction. The addition of H2O2 to the reaction mixture resulted in about an 8-fold increase of *OH production in the anaerobic reaction, but only about 1.5-fold in the aerobic reaction, indicating that e(-) generated by the photocatalytic reaction reduced H2O2 to produce *OH plus OH(-). On the other hand, D2O lowered the yield of *OH generation to 18% under air and 40% under Ar conditions, indicating the oxidation of H2O by h(+). The addition of Fe(III)-EDTA as an electron acceptor effectively increased *OH generation, 2.3-fold in the aerobic reaction and 8.4-fold in the anaerobic reaction, the yield in the latter exceeding that in the air-saturated reaction. PMID- 27392395 TI - Improved Bioassay Method for Plant Transformation Inhibitors. AB - A convenient and quantitative bioassay method for evaluating the efficiency of plant transformation by Agrobacterium tumefaciens is important to search plant transformation inhibitors, possible biochemical probes for study on its mechanism. Our previously reported method, in which the plant transformation had been detected by the expression of beta-glucuronidase in transformed plants, was improved. The difference between the previous and the improved methods is the use of suspension-cultured cells of Ageratum conyzoides as the host plant instead of Nicotiana tabacum BY-2; this alteration of the host enabled us to measure the beta-glucuronidase activity in plant cells not only fluorometrically but also colorimetrically. The enzyme activity expressed in the cells of A. conyzoides was nearly 100 times higher than that of N. tabacum BY-2, and was enough for detection by colorimetric measurement. The method, therefore, is useful for a convenient determination of inhibitory activity against plant transformation. PMID- 27392396 TI - Purification and Partial Identification of Bacteriocin ISK-1, a New Lantibiotic Produced by Pediococcus sp. ISK-1. AB - Bacteriocin ISK-1 is a proteinaceous inhibitory substance produced by Pediococcus sp. ISK-1 isolated from well-aged Nukadoko. Bacteriocin ISK-1 was purified by acid treatment, ammonium sulfate precipitation, cation-exchange chromatography, and reversed-phase HPLC from the culture supernatant of Pediococcus sp. ISK-1. Purification of bacteriocin ISK-1 resulted in a 30-fold increase in the specific activity and the recovery was 17%. Molecular mass of bacteriocin ISK-1 measured by fast atom bombardment-mass spectrometry was 2,960. The amino acid composition analysis of bacteriocin ISK-1 showed that it contained unusual amino acids such as lanthionine and/or 3-methyllanthionine, which is a characteristic of lantibiotics. The N-terminal amino acid sequence analysis indicated the first seven N-terminal amino acid residues as NH2-K-K-K-S-G-V-I. The primary sequence showed significant similarity to the lantibiotics lacticin 481 from Lactococcus lactis and variacin from Micrococcus varians, which suggests that bacteriocin ISK 1 is a novel lantibiotic belonging to a lacticin-481 type. PMID- 27392397 TI - NapA Na(+)/H(+) Antiporter as a Sodium Extrusion System Supplementary to the Vacuolar Na(+)-ATPase in Enterococcus hirae. AB - Enterococcus hirae has two sodium extrusion systems: the NapA Na(+)/H(+) antiporter and the vacuolar Na(+)-ATPase. We found that a NapA mutant, WD4, which is deficient in Na(+)/H(+) antiporter activity, grew well in the pH range of 6 to 10 up to 200 mM sodium. This was due to active, potential-independent sodium extrusion by the Na(+)-ATPase, which was induced under these conditions. The NapA Na(+)/H(+) antiporter is thus not a prerequisite for growth of E. hirae in the presence of sodium, but plays a supplementary role in sodium extrusion at acidic pH. PMID- 27392398 TI - Synthesis of Optically Active 1,4-Thiazane-3-carboxylic Acid via Optical Resolution by Preferential Crystallization of (RS)-2-Amino-3-[(2 chloroethyl)sulfanyl]propanoic Acid Hydrochloride. AB - Optically active 1,4-thiazane-3-carboxylic acid [TCA] was synthesized from cysteine via optical resolution by preferential crystallization. The intermediate (RS)-2-amino-3-[(2-chloroethyl)sulfanyl]propanoic acid hydrochlo-ride [(RS) ACS*HCl] was found to exist as a conglomerate based on its melting point, solubility and IR spectrum. (RS)-ACS*HCl was optically resolved by preferential crystallization to yield (R)- and (S)-ACS*HCl. (R)- and (S)-ACS*HCl thus obtained were recrystallized from a mixture of hydrochloric acid and 2-propanol, taking account of the solubility of (RS)-ACS*HCl, efficiently yielding both enantiomers in optically pure forms. (R)- and (S)-TCA were then respectively synthesized by the cyclization of (R)- and (S)-ACS*HCl in ethanol in the presence of triethylamine. PMID- 27392399 TI - Transglycosylation of Thiamin by Fungal beta-N-Acetylhexosaminidases. AB - A new thiamin glycoside, e.g., thiamin beta-D-2-deoxy-2-acetamidoglucopyranoside was prepared by transglycosylation by beta-N-acetylhexosaminidase from Aspergillus oryzae and characterized spectrally. Series of other fungal beta-N acetyl-hexosaminidases from A. awamori, A. tamari, A. terreus, and Penicillium oxalicum were shown to be able to synthesize the same compound in lower yields. PMID- 27392400 TI - Simple Synthesis of Both Enantiomers of the C7-C12 Segment of Epothilones. AB - Both enantiomers of the C7-C12 segment (3 and 4) of antitumor antibiotics epothilones (1and 2) were synthesized from methyl (R)- and (S)-3-hydroxy-2 methylpropionate (5 and 6) in five steps in a fair yield. PMID- 27392401 TI - Purification of Pumpkin Glutathione S-Transferase Species Specifically Present in Cultured Cells Treated by Excessive Concentration of 2,4-Dichlorophenoxyacetic Acid but Absent in Normal Plants. AB - Pugc is a unique glutathione S-transferase subunit species that is absent in normal pumpkin plants, but GST3c (homodimer of Pugc) accumulates in cultured pumpkin cells treated with 40 ppm 2,4-dichlorophenoxyacetic acid for six days. GST3c was purified by DEAE-cellulose, hydroxylapatite, and S-hexylglutathione agarose column chromatography, and its homogeneity was confirmed by SDS-PAGE analysis. The specific activity of GST3c was 124 MUmol/min/mg protein with 1 chloro-2,4-dinitrobenzene. This was higher than those of the other plant and animal glutathione S-transferases. Mouse antiserum raised against the purified GST3c recognized only Pugc, but not Puga, Pugb, nor Pugd when the reactivity of pumpkin glutathione S-transferase subunits was tested. PMID- 27392402 TI - Lipase-catalyzed Asymmetric Synthesis of Enantiomerically Pure (2S,4aS,8S)-4a,8 Dimethyl-2,3,4,4a,5,6,7,8-octahydro-2-naphthalenol. AB - Enantiomerically pure (2S,4aS,8S)-(+)-4a,8-dimethyl-2,3,4,4a,5,6,7,8-octahydro-2 naphthalenol (3), a key intermediate in the synthesis of natural geosmin (1), was prepared by enzymatic kinetic resolution. When racemic 3 was submitted to lipase (PS-30)-catalyzed asymmetric acetylation, employing vinyl acetate as the acyl donor, requisite product (+)-3 with a high enantiomeric excess was attained as the remaining alcohol. Recrystallization resulted in an enantiomerically pure sample. PMID- 27392403 TI - Promotion by a Peptidyl Growth Factor, Phytosulfokine, of Chlorophyll Formation in Etiolated Cotyledon of Cucumber. AB - We examined the effects of a peptidyl growth factor, phytosulfokine-alpha (PSK alpha), isolated from conditioned medium and known to induce the proliferation of single mesophyll cells of asparagus, and its derivatives on chlorophyll formation in etiolated cotyledons of cucumber after illumination. The chlorophyll content was increased by PSK-alpha treatment. Chlorophyll-content increases were not observed following either [2-5]PSK or Tyr-SO3H treatment. There was no difference between the PSK-alpha treatments and water controls on increasing rate of fresh weights of cotyledons. These results suggest that PSK-alpha has the effect of elevating the chlorophyll content in the cells. PMID- 27392404 TI - Thermal Isomerization of All-trans-Lutein in a Benzene Solution. AB - Four major cis-lutein isomers could be identified after thermal isomerization of all-trans-lutein in a benzene solution system; namely, 13'-, 13-, 9'- and 9-cis luteins. Using both all-trans-lutein and a mixture of these purified cis-luteins as starting materials, the quantitative changes determined by HPLC response show that this thermal isomerization was a reversible reaction. The equilibrium constants (k C ) of 13'- and 13-cis-luteins were higher than those of 9'-, and 9 cis-luteins, suggesting that the amount formed of the former isomers was higher than that of the latter. PMID- 27392405 TI - Novel Cyclohexene Compound from Lasiodiplodia theobromae IFO 31059. AB - A novel cyclohexene compound (1), which is structurally related to theobroxide (2), was isolated from a culture filtrate of the fungus, Lasiodiplodia theobromae IFO 31059. The potato micro-tuber-inducing activity of this compound was observed at a concentration of 10(-3) M in the medium, whereas theobroxide (2) showed its activity at 10(-5) M. PMID- 27392406 TI - Prevention of Initial Supercooling in Progressive Freeze-concentration. AB - A physical method is proposed that uses a cooling plate with many small holes to prevent initial supercooling in progressive freeze-concentration, and thus avoid serious contamination of the ice produced. The higher chance for ice nucleation of the water molecules in the holes due to the temperature gradient in the cooling plate resulted in the initial supercooling being completely prevented. Accordingly, the purity of the ice initially formed was substantially improved when compared with that by the standard vessel without holes in the cooling plate. PMID- 27392407 TI - Biosynthesis of striatol in cultured cells of liverwort, Ptycanthus striatus. AB - NMR analyses of striatol produced by suspension-cultured cells of liverwort, Ptycanthus striatus, in the presence of [2-(13)C]- and [4,4-(2)H2]-MVAs confirmed proton-catalyzed cyclization between the distal and central double bonds in FPP and a concerted series of 1,2-migrations of hydrogen and a methyl group, with subsequent elimination of a proton. PMID- 27392408 TI - Corrigendum to "Inhibition of AKT sensitizes chemoresistant ovarian cancer cells to cisplatin by abrogating S and G2/M arrest" (Exp. Mol. Pathol. 2016 100(3) 506 13). PMID- 27392409 TI - In Situ Tissue Engineering: Seducing the Body to Regenerate. PMID- 27392410 TI - Differences in nulliparous caesarean section rates across models of care: a decomposition analysis. AB - BACKGROUND: To evaluate the extent of the difference in elective (ELCS) and emergency (EMCS) caesarean section (CS) rates between nulliparous women in public maternity hospitals in Ireland by model of care, and to quantify the contribution of maternal, clinical, and hospital characteristics in explaining the difference in the rates. METHODS: Cross-sectional analysis using a combination of two routinely collected administrative databases was performed. A non-linear extension of the Oaxaca-Blinder method is used to decompose the difference between public and private ELCS and EMCS rates into the proportion explained by the differences in observable maternal, clinical, and hospital characteristics and the proportion that remains unexplained. RESULTS: Of the 29,870 babies delivered to nulliparous women, 7,792 were delivered via CS (26.1 %), 79.6 % of which were coded as EMCS. Higher prevalence of ELCS was associated with breech presentation, other malpresentation, and the mother being over 40 years old. Higher prevalence of EMCS was associated with placenta praevia or placental abruption, diabetes (pre-existing and gestational), and being over 40 years old. The private model of care is associated with ELCS and EMCS rates 6 percentage points higher compared than the public model of care but this differential is insignificant in the fully adjusted models for EMCS. Just over half (53 %) of the 6 percentage point difference in ELCS rates between the two models of care can be accounted for by maternal, clinical and hospital characteristics. Almost 80 % of the difference for EMCS can be accounted for. CONCLUSIONS: The majority of the difference in EMCS rates across models of care can be explained by differing characteristics between the two groups of women. The main contributor to the difference was advancing maternal age. The unexplained component of the difference for ELCS is larger; an excess private effect remains after accounting for maternal, clinical, and hospital characteristics. This requires further investigation and may be mitigated in future with the introduction of clinical guidelines related to CS. PMID- 27392412 TI - Complex morphology of gastrin-releasing G-cells in the antral region of the mouse stomach. AB - Gastrin-releasing enteroendocrine cells (G-cells) are usually described as flask shaped cells with a large base and a small apical pole, integrated in the epithelium lining the basal region of the antral invaginations in the stomach. By means of a transgenic mouse line in which the enhanced version of GFP is endogenously expressed under the control of a gastrin promoter, we have analyzed the spatial distribution and morphological features of G-cells. We found that G cells were not only located at the basal region of the invagination but to a lesser extent also at the upper region. Visualization of the entire cellular morphology revealed that G-cells show complex morphologies. Basally located G cells are roundish-shaped cells which project a prominent apical process towards the lumen and extend basal protrusions containing the hormone gastrin that were frequently found in close proximity to blood vessels and occasionally in the vicinity of nerve fibers. Inspection of G-cells in the upper region of antral invaginations disclosed a novel population of G-cells. These cells have a spindle like contour and long apical and basal processes which extend vertically along the antral invagination, parallel to the lumen. This G-cell population seems to be in contact with a network of nerve fibers. While the functional role of these untypical G-cells is still elusive, the results of this study provide some useful indications to possible roles of these G-cells. PMID- 27392411 TI - Long Non-Coding RNAs (lncRNAs) of Sea Cucumber: Large-Scale Prediction, Expression Profiling, Non-Coding Network Construction, and lncRNA-microRNA-Gene Interaction Analysis of lncRNAs in Apostichopus japonicus and Holothuria glaberrima During LPS Challenge and Radial Organ Complex Regeneration. AB - Long non-coding RNA (lncRNA) structurally resembles mRNA but cannot be translated into protein. Although the systematic identification and characterization of lncRNAs have been increasingly reported in model species, information concerning non-model species is still lacking. Here, we report the first systematic identification and characterization of lncRNAs in two sea cucumber species: (1) Apostichopus japonicus during lipopolysaccharide (LPS) challenge and in heathy tissues and (2) Holothuria glaberrima during radial organ complex regeneration, using RNA-seq datasets and bioinformatics analysis. We identified A. japonicus and H. glaberrima lncRNAs that were differentially expressed during LPS challenge and radial organ complex regeneration, respectively. Notably, the predicted lncRNA-microRNA-gene trinities revealed that, in addition to targeting protein coding transcripts, miRNAs might also target lncRNAs, thereby participating in a potential novel layer of regulatory interactions among non-coding RNA classes in echinoderms. Furthermore, the constructed coding-non-coding network implied the potential involvement of lncRNA-gene interactions during the regulation of several important genes (e.g., Toll-like receptor 1 [TLR1] and transglutaminase-1 [TGM1]) in response to LPS challenge and radial organ complex regeneration in sea cucumbers. Overall, this pioneer systematic identification, annotation, and characterization of lncRNAs in echinoderm pave the way for similar studies and future genetic, genomic, and evolutionary research in non-model species. PMID- 27392413 TI - Chlorhexidine: Patient Bathing and Infection Prevention. AB - Healthcare-associated infections (HAIs) are an important cause of morbidity and mortality in the USA. They are associated with a substantial increase in health care costs each year. Fortunately, many HAIs are preventable, and their eradication is a national priority. Chlorhexidine (CHG) bathing has been used as an infection prevention measure, either alone or bundled with other interventions, with mostly beneficial results. The recent surge in its use as an agent of choice for skin antisepsis has lead to concerns over emerging resistance among microorganisms. Moreover, compliance with CHG-bathing protocols is not routinely monitored. Policies developed to determine the best infection prevention practice must consider that a "one-size-fits-all" strategy may lead to the selection of CHG-tolerant microorganisms, thereby emphasizing the need for more robust guidelines and additional studies on the role of chlorhexidine bathing for the prevention of HAIs. PMID- 27392414 TI - Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes. AB - Toll-like receptors (TLRs) are pattern recognition receptors mainly expressed by cells of the immune system but also by epithelial tumor cells. Little is known about expression patterns of TLR genes in breast tumors, and their clinical significance is unclear. The aim of our study was to investigate expression of TLRs pathway components in pre-invasive breast lesions and invasive breast carcinomas (IBCs). We used RT-PCR assays to quantify mRNA levels of the 10 TLR genes and genes involved in TLR pathways in 350 breast tumors from patients with known clinical/pathological status and long-term outcome. Sets of 158 breast samples were also analyzed by immunochemistry including; 40 early noninvasive breast lesions, 38 IBCs and 80 triple negative carcinomas subtype (TNCs). We identified TLR9 as the major TLR gene family member upregulated in breast tumors and more particularly in TNCs. Immunohistochemical studies demonstrated that TLR9 protein was expressed in tumor epithelial and stromal cells of the TLR9 mRNA overexpressing tumors. TLR9 overexpression appears very early during breast carcinogenesis. High TLR9 levels were associated with favorable outcome in the TNC sub-group. TLR9 overexpression was associated with alterations of down-stream components of the TLR9 signaling pathway, epithelio-mesenchymal transition (EMT) induction and EGFR pathway deregulation. TNCs with TLR9 overexpression were significantly correlated with development of a fibrous and inflammatory microenvironment with variable status of nuclear phosphoSTAT3. Our results suggest that TLR9 could play a role in TNC carcinogenesis and could be useful as predictive biomarker and therapeutic target. PMID- 27392417 TI - Direct and Indirect Effects of Heavy Alcohol Use on Clinical Outcomes in a Longitudinal Study of HIV Patients on ART. AB - In a cohort of patients receiving care for HIV, we examined longitudinally the impact of past 30-day frequency of heavy drinking (consuming 5+ drinks on one occasion) on HIV-related (detectable viral load and CD4+ T cell count) and non HIV-related (hemoglobin and biomarkers of kidney function and liver fibrosis) clinical outcomes and the extent to which these effects were due to reduced antiretroviral therapy (ART) adherence. Data came from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy. Between March 2004 and June 2006, 533 individuals receiving ART were recruited and followed every 6 months for six years. Using longitudinal mediation analysis, we estimated natural direct effects (NDE) of heavy drinking frequency (never, 1-3 times, or 4+ times in the past 30 days) on clinical outcomes and natural indirect effects (NIE) mediated via ART adherence. A one-level increase in heavy drinking frequency had a significant negative NDE on CD4+ T-cell counts (-10.61 cells/mm3; 95 % CI [-17.10, -4.12]) and a significant NIE through reduced ART adherence of 0.72 cells/mm3 (95 % CI [-1.28, -0.15]), as well as a significant NIE on risk of detectable viral load (risk ratio = 1.03; 95 % CI [1.00, 1.05]). Heavy drinking had a significant detrimental NIE on a combined index of 5-year mortality risk and detrimental NDE and total effect on a biomarker of liver fibrosis. Heavy drinking has deleterious effects on multiple clinical outcomes in people living with HIV, some of which are mediated through reduced ART adherence. PMID- 27392418 TI - Views on clinical trial recruitment, biospecimen collection, and cancer research: population science from landscapes of the Haudenosaunee (People of the Longhouse). AB - Biomedical research in culturally distinct communities is often a challenge. Potential barriers to participation occur because science is presented in a format that lacks cultural acknowledgement. Investigations may also fail to showcase beneficial relevance to the communities or include them in true partnership. The history of biomedical research within Native American societies has been complicated by these issues. Historical trauma among many Native groups sometimes transcends into contemporary challenges in both recruitment to and participation particularly in biobanking research. The participants for this study included members of the Haudenosaunee, the People of the Longhouse. Native Americans, including the Haudenosaunee, endure some of the worst health disparities in the country. These include high rates of cancer, obesity, and diabetes which may be linked at least partially to genetic predisposition. Results from a Haudenosaunee urban population shared response on ways to improve recruitment strategies for biospecimen, cancer, and other health-related clinical trials. Mixed methods approaches were used, and community responses indicated the importance of creating trust through respectful partnership; promoting culturally appropriate recruitment materials; the need for a greater understanding of consenting and signature processes; the necessity for concise summary sheets; and a desire to have information that community member understand. Discussion items also include international Indigenous perspectives to biobanking and genetic related health disparity research. PMID- 27392420 TI - Pathological Features and Pathogenesis of the Endomyocardial Form of Restrictive Cardiomyopathy in Cats. AB - This study reports pathological and molecular features in 41 cases of feline restrictive cardiomyopathy (RCM). Grossly, there were patchy or diffuse areas of endocardial thickening affecting the left ventricle. The more common patchy endocardial lesions occurred as large trabecular or irregular broad bands of fibrous tissue bridging the left ventricular free wall and ventricular septum. Microscopically, regardless of the gross pattern, the thickened endocardium contained various numbers of stellate, spindle-shaped or elongated mesenchymal cells surrounded by fibrous connective tissue. Immunohistochemical findings were indicative of smooth muscle differentiation in mesenchymal cells. These cells proliferated vigorously and produced alcian blue-positive ground substance and collagen fibres; it was considered that the mesenchymal cells contributed to the formation of the endocardial lesions. In addition, multiple left ventricular 'false tendons' were invariably included within the trabecular or broad fibrous bands, providing a framework for formation of those bands. Evidence of endocarditis or endomyocarditis was lacking in all 41 cases, and no viral genomes were detected in any of the DNA or RNA samples obtained from 14 of the hearts. These observations suggest that any relationship between feline RCM and a virus induced inflammatory response seems unlikely. PMID- 27392419 TI - The effects of topical nasal steroids on continuous positive airway pressure compliance in patients with obstructive sleep apnea: a systematic review and meta analysis. AB - OBJECTIVES: The purpose of the study was to conduct a systematic review and meta analysis in patients with obstructive sleep apnea (OSA), evaluating effects of topical nasal steroids on continuous positive airway pressure (CPAP) machine use and nasal symptoms. SEARCH METHODS: Data source: A comprehensive search of Pubmed, Scopus, Web of Science, and the Cochrane Library was performed through April 2016. Manual searches and subject matter expert input were also obtained. Studies assessing effects of nasal steroids on CPAP machine use in adults, which reported quantitative outcome data of CPAP compliance, were included. RESULTS: Two studies (144 patients) met inclusion criteria. Both were randomized, placebo controlled clinical trials (RCT). Pooled fixed effects analysis did not identify a statistically significant difference between both the groups for average duration of CPAP machine use per night. But there was an overall increase in the usage of 0.4 h (95 % confidence interval (CI) (-0.20, 1.00); P = 0.19) in favor of nasal steroids. Difference of percentage of nights with CPAP use was not demonstrated (mean difference 0.06, 95 % CI (-0.27, 0.39); P = 0.71). There was also no significant difference in nasal symptoms (mean difference 0.63, 95 % CI ( 0.11, 1.36), P = 0.1). CONCLUSION: Nasal steroids showed benefits on CPAP use, but did not reach statistical significance. Data was based on meta-analysis of RCTs of 4-week follow-up in unselected OSA patients. Future controlled studies with selected group and longer follow-up duration are needed to confirm the benefits of nasal steroid on CPAP compliance in OSA patients. PMID- 27392421 TI - Multicentric Benign Epithelial Inclusions in a Free-ranging Risso's Dolphin (Grampus griseus). AB - This report describes the histological and immunohistochemical features of multicentric, benign, epithelial inclusions (BEIs) in a free-ranging, adult, female Risso's dolphin (Grampus griseus). The differential diagnoses included ectopic hamartomatous epithelial inclusions, non-Mullerian choristoma, Mullerian choristoma and low-grade metastatic carcinoma/mesothelioma. The most likely diagnosis of such BEIs was multicentric, embolic, reactive mesothelium, as suggested by cytomorphological and immunophenotypical features of the BEIs, the occurrence of focal pleural rupture and the immunophenotype of the pleural mesothelium. The former represents a pathological condition not previously reported in a marine mammal species, rarely described in animals, and relatively infrequently recognized in man. PMID- 27392422 TI - WITHDRAWN: Clinical Signs, Neuroanatomical Distribution and Histopathological Characterisation of Meningoencephalitis in Wild Red Foxes (Vulpes vulpes) Associated with a Novel fox Circovirus. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27392423 TI - Multiple Cutaneous Metastasis of a Malignant Leydig Cell Tumour in a Dog. AB - A testicular Leydig cell tumour associated with metastatic disease is reported in a dog. An enlarged testis and three cutaneous nodules resected from an 11-year old golden retriever were submitted for histopathological examination. Both testicular and cutaneous lesions showed identical morphological and cytological changes. Immunohistochemical labelling for expression of inhibin-alpha and calretinin confirmed the Leydig origin of the cutaneous neoplastic population. Based on the morphological and immunohistochemical findings, a final diagnosis of multiple cutaneous metastasis of a malignant testicular Leydig cell tumour was made. PMID- 27392424 TI - Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide. AB - BACKGROUND & AIMS: Studies assessing alcohol as a population level risk factor for cirrhosis typically focus on per capita consumption. However, clinical studies indicate that daily intake is a strong predictor of alcoholic cirrhosis. We aimed to identify the determinants of alcohol's contribution to the global cirrhosis burden and to evaluate the influence of daily drinking on a population level. METHODS: We performed a comprehensive analysis of the WHO 2014 Global Status Report on Alcohol and Health. We categorized countries by heavy or moderate drinking based on daily consumption, using U.S. Department of Agriculture definitions of heavy drinking. Additional data on cirrhosis cofactors were also obtained. Uni- and multivariate models were fitted to identify independent predictors of the alcohol-attributable fraction of cirrhosis. RESULTS: The WHO 2014 Report found that half of cirrhosis mortality worldwide is attributable to alcohol, approximating 60% in North America and Europe. In an integrative multivariate model, the designation of countries by moderate or heavy daily drinking had the strongest influence on the weight of alcohol in the cirrhosis burden. The relative contribution from alcohol increased by 11% with a transition from the moderate to heavy classification (p<0.001). Importantly, drinking patterns such as heavy episodic drinking and the type of alcohol did not independently predict the alcohol-attributable fraction of cirrhosis. CONCLUSIONS: Heavy daily drinking on a population level significantly influences the weight of alcohol in the cirrhosis burden. Reducing heavy drinking should be considered as an important target for public health monitoring and policies. LAY SUMMARY: We carried out an analysis of the WHO 2014 Global Status Report on Alcohol and Health, and categorized countries by their level of drinking (heavy or moderate). We found that half of the global cirrhosis cases, and 60% in both North America and Europe are associated with alcohol intake. We concluded that on a population level heavy daily drinking significantly influences the impact of alcohol on the cirrhosis burden. PMID- 27392425 TI - Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma. PMID- 27392426 TI - Exercise in NAFLD: Just do it. PMID- 27392427 TI - [Not Available]. AB - STUDY'S AIM: This study aims a more efficient follow-up of the safety of medicines with human usage on the Ivory Coast territory. METHOD: The structure responsible for pharmacovigilance in Ivory Coast i.e. DPM listed the medicinal alerts from 2001 till 2010. RESULTS: It emerges 237 medicinal alerts among which 145 stops of marketing, 55 withdrawals of lots, 33 information notes and 4 levying of suspension of medicines. These alerts result mainly from pharmaceutical companies (49%) and the French Drug Agency or ANSM (ex-Afssaps) (43%). They mainly concern drugs of infectious target (22%) and pneumology (18%) and their motivations are so much industrial with mainly commercial reasons (27%) as of pharmacovigilance dominated by unfavorable profit/risk connections. CONCLUSION: These results constitute an important database for the survey of the medicines market in Ivory Coast and an additional motivation to accelerate the implementation of a real national center of pharmacovigilance. PMID- 27392428 TI - [Not Available]. PMID- 27392429 TI - An attenuated EMCV-HB10 strain acts as a live viral vector delivering a foreign gene. AB - We successfully constructed a full-length cDNA infectious clone of the encephalomyocarditis virus (EMCV) HB10 strain and obtained a partially attenuated rEMCV-C9 virus with a shorter poly(C) tract. Our results showed that the length of the EMCV-HB10 poly(C) tract was related to the pathogenicity of the EMCV-HB10 strain in vivo. Using pEMCV-C9 as the backbone, we constructed the novel viral vector pC9-MCS-?2A by inserting a cDNA fragment containing a 127 amino acid deletion in the 2A protein, a primary cleavage cassette, a FLAG tag and a multiple cloning site (MCS) at the junction of VP1 and ?2A. Additionally, the enhanced green fluorescent protein (egfp) gene was cloned into the MCS of pC9-MCS ?2A to test its capacity to express foreign proteins. Insertion of the egfp gene did not affect viral replication, and a decrease in EGFP expression was observed within five serial passages. Furthermore, we found that rC9-EGFP-?2A was avirulent in vivo, induced neutralizing antibody production and conferred protective immune responses against lethal challenge with EMCV in mice. Taken together, our results demonstrated that we had constructed an attenuated live vector based on an EMCV-HB10 strain with two modified critical virulence factors (the poly(C) tract and 2A protein) that could be used as a candidate live vaccine and a potential live viral vector for foreign antigen delivery. PMID- 27392430 TI - Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial. AB - BACKGROUND: Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. METHODS: A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (2(5)) experimental conditions after downloading the 'Drink Less' app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. DISCUSSION: This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and evaluated against a minimal control in a definitive randomised control trial with long-term outcomes. TRIAL REGISTRATION: ISRCTN40104069 Date of registration: 10/2/2016. PMID- 27392433 TI - Acinetobacter pragensis sp. nov., found in soil and water ecosystems. AB - This study aimed to define the taxonomic status of a novel, phenetically distinct group of seven strains belonging to the genus Acinetobacter, which were isolated from environmental soil and water samples collected in Central Bohemia, Czech Republic. Comparative sequence analyses of the 16S rRNA, gyrB and rpoB genes showed that all these strains formed respective tight clusters (intracluster sequence similarities of >=99.8, >=98.1 and >=98.3 %, respectively), which were distant from all known Acinetobacter species (<=98.2, <=84.0 and <=88.9 %, respectively). The average nucleotide identity and digital DNA-DNA hybridization values (<=83.5 and <=27.4 %, respectively) between the whole-genome sequence of a group representative (strain ANC 4149T) and those of known taxa were far below the thresholds used to discriminate between bacterial species. The seven strains also formed a tight and distinct cluster based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization time-of-flight MS and could be distinguished from all other members of the genus Acinetobacter by the combination of their ability to assimilate glutarate and l-tartrate and inability to grow at 37 degrees C and on l-aspartate. It is concluded that the seven strains represent a novel species for which the name Acinetobacter pragensis sp. nov. is proposed. The type strain is ANC 4149T (=CCM 8637T=CCUG 67962T=CNCTC 7530T). PMID- 27392431 TI - NeuroRDF: semantic integration of highly curated data to prioritize biomarker candidates in Alzheimer's disease. AB - BACKGROUND: Neurodegenerative diseases are incurable and debilitating indications with huge social and economic impact, where much is still to be learnt about the underlying molecular events. Mechanistic disease models could offer a knowledge framework to help decipher the complex interactions that occur at molecular and cellular levels. This motivates the need for the development of an approach integrating highly curated and heterogeneous data into a disease model of different regulatory data layers. Although several disease models exist, they often do not consider the quality of underlying data. Moreover, even with the current advancements in semantic web technology, we still do not have cure for complex diseases like Alzheimer's disease. One of the key reasons accountable for this could be the increasing gap between generated data and the derived knowledge. RESULTS: In this paper, we describe an approach, called as NeuroRDF, to develop an integrative framework for modeling curated knowledge in the area of complex neurodegenerative diseases. The core of this strategy lies in the usage of well curated and context specific data for integration into one single semantic web-based framework, RDF. This increases the probability of the derived knowledge to be novel and reliable in a specific disease context. This infrastructure integrates highly curated data from databases (Bind, IntAct, etc.), literature (PubMed), and gene expression resources (such as GEO and ArrayExpress). We illustrate the effectiveness of our approach by asking real world biomedical questions that link these resources to prioritize the plausible biomarker candidates. Among the 13 prioritized candidate genes, we identified MIF to be a potential emerging candidate due to its role as a pro-inflammatory cytokine. We additionally report on the effort and challenges faced during generation of such an indication-specific knowledge base comprising of curated and quality-controlled data. CONCLUSION: Although many alternative approaches have been proposed and practiced for modeling diseases, the semantic web technology is a flexible and well established solution for harmonized aggregation. The benefit of this work, to use high quality and context specific data, becomes apparent in speculating previously unattended biomarker candidates around a well-known mechanism, further leveraged for experimental investigations. PMID- 27392432 TI - Reliability of plasma lipopolysaccharide-binding protein (LBP) from repeated measures in healthy adults. AB - Plasma lipopolysaccharide-binding protein (LBP), a measure of internal exposure to bacterial lipopolysaccharide, has been associated with several chronic conditions and may be a marker of chronic inflammation; however, no studies have examined the reliability of this biomarker in a healthy population. We examined the temporal reliability of LBP measured in archived samples from participants in two studies. In Study one, 60 healthy participants had blood drawn at two time points: baseline and follow-up (either three, six, or nine months). In Study two, 24 individuals had blood drawn three to four times over a seven-month period. We measured LBP in archived plasma by ELISA. Test-retest reliability was estimated by calculating the intraclass correlation coefficient (ICC). Plasma LBP concentrations showed moderate reliability in Study one (ICC 0.60, 95 % CI 0.43 0.75) and Study two (ICC 0.46, 95 % CI 0.26-0.69). Restricting the follow-up period improved reliability. In Study one, the reliability of LBP over a three month period was 0.68 (95 % CI: 0.41-0.87). In Study two, the ICC of samples taken <=seven days apart was 0.61 (95 % CI 0.29-0.86). Plasma LBP concentrations demonstrated moderate test-retest reliability in healthy individuals with reliability improving over a shorter follow-up period. PMID- 27392435 TI - Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. AB - Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and lung cancer's drug resistance. In this study, we examined the effect of Jinfukang (JFK), an effective herbal medicine against lung cancer, on DDP induced cytotoxicity in lung cancer cells. Morphologically, we observed that JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that the combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found that the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines, such as NCI-H1975, NCI-H1650, and NCI H2228. Particularly, we demonstrated that AIFM2 is activated by the combined treatment of JFK and DDP and partially mediates the synergistic pro-apoptosis effect. Collectively, this study not only offered the first evidence that JFK promotes DDP-induced cytotoxicity, and activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress, but also provided a novel insight for improving cytotoxicity by combining JFK with DDP to treat lung cancer cells. PMID- 27392434 TI - In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity. AB - BACKGROUND: Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) loss of function is frequently detected in advanced colorectal cancer. Its detection is thought to have prognostic significance and it is being considered to predict responsiveness to anti-EGFR therapy. Unfortunately, while immunohistochemical assessment of PTEN expression is widespread, it lacks standardization and the results are hardly comparable across the available publications. METHODS: Retrospectively collected, formalin-fixed and paraffin-embedded colorectal tumor tissue samples from 55 patients were combined into tissue microarray (TMA) blocks. We used three different PTEN antibodies to determine the frequency, intensity and intracellular pattern of PTEN immunohistochemical labeling: Neomarkers, Dako and CellSignaling. We evaluated the aforementioned parameters in selected regions of colorectal cancers and in their lymph node metastases by using three scoring methods that take into consideration both staining frequency and intensity (H1-H3-score). We also evaluated intracellular localization. RESULTS: The Dako and CellSignaling antibodies stained predominantly cytoplasms, while the Neomarkers antibody specifically stained cell nuclei. PTEN H-scores were significantly lower in all tumor areas as compared to the normal colonic mucosa based on staining with the DAKO and CellSignaling antibodies. Intratumoral regional differences or differences between matching tumors and metastases were not detected with any of the antibodies. Neither Dako, neither CellSignaling, nor the Neomarkers antibodies revealed a significant correlation between PTEN expression and pT, Dukes/MAC and clinical stage. KRAS status, histological grade correlated with PTEN H-scores based on staining with the Neomarkers antibody. PTEN H-scores did not correlate with MMR status. PTEN H-scores did not show any correlation with relapse-free survival based on staining with either antibody. CONCLUSIONS: While PTEN expression decreased in colorectal cancer according to two antibodies, neither of the three applied PTEN antibodies could justify significant correlation with clinicopathological data, nor had prognostic value. Thus, we might conclude that immunohistochemical PTEN investigation remains a challenge requiring more standardized evaluation on larger number of cases to clarify its utility as a prognostic and predictive tool in CRC. The standardization of immunohistochemical method is key in the evaluation process, which is further discussed. PMID- 27392436 TI - Long-term effect of heavy-metal pollution on diversity of gastrointestinal microbial community of Bufo raddei. AB - Gastrointestinal (GI) microbiota plays a very important role in maintaining its host's health. However, the effects of environmental contamination on the GI microbiota homeostasis of amphibians have not yet been reported. The present study reveals the long-term effect of natural heavy-metal pollution on the GI microbial community diversity and structural changes of Bufo raddei (B. raddei). Basing on the 16S rRNA sequencing method, the GI microbiota of B. raddei from a heavily heavy-metal-polluted area (Baiyin, (BY)) and a relatively unpolluted area (Liujiaxia, (LJX)) were profiled. The results showed that heavy-metal pollution had caused significant shifts in the composition of the GI microbiota both at the phylum and genus levels. Specifically, Bacteroidetes dominated in the GI tract of B. raddei from BY, while Tenericutes was much more common in those from LJX. The ratio of Firmicutes/Bacteroidetes and the proportion of probiotics in the GI microbiota of B. raddei from BY were reduced compared to those from LJX, as well. Heavy-metal pollution also induced in a reduction of species diversity and decreased proportion of unique operational taxonomic units in the GI tract. In short, our results demonstrate that long-term heavy-metal exposure re-shaped the composition and decreased the species diversity of GI microbiota of B. raddei; our results also represent a novel approach to uncover the toxic effects of pollution on amphibians. PMID- 27392437 TI - Fluoxetine and the mitochondria: A review of the toxicological aspects. AB - Fluoxetine (a selective serotonin reuptake inhibitor (SSRI)) is used as an antidepressant by modulating the levels of serotonin in the synaptic cleft. Nevertheless, fluoxetine also induces undesirable effects, such as anxiety, sexual dysfunction, sleep disturbances, and gastrointestinal impairments. Fluoxetine has been viewed as an agent that may interfere with cell fate by triggering apoptosis. On the other hand, fluoxetine intake has been associated with increased cancer risk. Nonetheless, data remain contradictory and no conclusions were taken. Several studies demonstrated that fluoxetine interacts with mitochondria triggering apoptosis and/or altering mitochondrial function by modulating the activity of respiratory chain components and enzymes of the Krebs cycle. Furthermore, fluoxetine affects mitochondria-related redox parameters in different experimental models. In this review, data demonstrating the effects of fluoxetine upon mammalian mitochondria are described and discussed, as well as several unsolved questions in this field of research are addressed. A separate section deals with future needs regarding the research involving the impact of fluoxetine treatment upon mitochondria and mitochondria-related signaling. PMID- 27392439 TI - [Does intraoperative lung-protective ventilation reduce postoperative pulmonary complications?]. AB - BACKGROUND: Recent studies show that intraoperative protective ventilation is able to reduce postoperative pulmonary complications (PPC). OBJECTIVES: This article provides an overview of the definition and ways to predict PPC. We present different factors that lead to ventilator-induced lung injury and explain the concepts of stress and strain as well as driving pressure. Different strategies of mechanical ventilation to avoid PPC are discussed in light of clinical evidence. MATERIALS AND METHODS: The Medline database was used to selectively search for randomized controlled trials dealing with intraoperative mechanical ventilation and outcomes. RESULTS: Low tidal volumes (VT) and high levels of positive end-expiratory pressure (PEEP), combined with recruitment maneuvers, are able to prevent PPC. Non-obese patients undergoing open abdominal surgery show better lung function with the use of higher PEEP levels and recruitment maneuvers, however such strategy can lead to hemodynamic impairment, while not reducing the incidence of PPC, hospital length of stay and mortality. An increase in the level of PEEP that results in an increase in driving pressure is associated with a greater risk of PPC. CONCLUSIONS: The use of intraoperative VT ranging from 6 to 8 ml/kg based on ideal body weight is strongly recommended. Currently, a recommendation regarding the level of PEEP during surgery is not possible. However, a PEEP increase that leads to a rise in driving pressure should be avoided. PMID- 27392438 TI - Targeting advanced glycation with pharmaceutical agents: where are we now? AB - Advanced glycation end products (AGEs) are the final products of the Maillard reaction, a complex process that has been studied by food chemists for a century. Over the past 30 years, the biological significance of advanced glycation has also been discovered. There is mounting evidence that advanced glycation plays a homeostatic role within the body and that food-related Maillard products, intermediates such as reactive alpha-dicarbonyl compounds and AGEs, may influence this process. It remains to be understood, at what point AGEs and their intermediates become pathogenic and contribute to the pathogenesis of chronic diseases that inflict current society. Diabetes and its complications have been a major focus of AGE biology due to the abundance of excess sugar and alpha dicarbonyls in this family of diseases. While further temporal information is required, a number of pharmacological agents that inhibit components of the advanced glycation pathway have already showed promising results in preclinical models. These therapies appear to have a wide range of mechanistic actions to reduce AGE load. Some of these agents including Alagebrium, have translated successfully to clinical trials, while others such as aminoguanidine, have had undesirable side-effect profiles. This review will discuss different pharmacological agents that have been used to reduce AGE burden in preclinical models of disease with a focus on diabetes and its complications, compare outcomes of those therapies that have reached clinical trials, and provide further rationale for the use of inhibitors of the glycation pathway in chronic diseases. PMID- 27392440 TI - [Aggression and subjective risk in emergency medicine : A survey]. AB - BACKGROUND: Healthcare personnel may be faced with different degrees of violence and aggression, particularly concerning preclinical care. However, systematic data with respect to the frequency and type of violence in emergency medicine in Germany has not been researched. METHODS AND OBJECTIVES: At an anesthesiology congress, an anonymous survey was distributed about the different kinds and extent of violent acts that the participants had experienced during their work in emergency medicine. Moreover, the participants' subjective feelings toward professional and personal safety when handling emergency cases were explored. RESULTS: Every fourth participant in the survey (25.2 %) had experienced occupational physical violence within the last 12 months. Verbal harassment or insults within the last twelve months were reported by 58.2 % of the participants. While 80 % of the participants feel "entirely" or "mostly" safe with regard to the professional aspect of their occupation, personal safety was considered "entirely" in only 9.3 % and "mostly" in 46.4 % of the cases. Nearly every third participant (31.8 %) feels only "partially" safe and every eighth participant feels "rather not" or "not at all" safe during emergency medicine missions. Men appreciate their expertise as well as their personal safety more so than women (p < 0.001). CONCLUSION: Aggression and violence towards healthcare personnel in emergency medicine occur on a regular basis in the German healthcare system. Little research has been conducted in this area, so the issue has not yet been perceived as a relevant problem. Appropriate training for healthcare personnel in emergency medicine should be targeted at developing the skills needed when encountered with aggression and occupational violence. PMID- 27392442 TI - Thirty-day outcomes for posterior fossa decompression in children with Chiari type 1 malformation from the US NSQIP-Pediatric database. AB - PURPOSE: The multicenter National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database maintained by the American College of Surgeons was used to describe 30-day outcomes following Chiari type 1 decompression in children and to identify risk factors for readmission, reoperation, and perioperative complications. METHODS: We identified patients aged 0-18 years who underwent posterior cranial fossa decompression for Chiari type 1 malformation in 2012, 2013, and 2014 in the NSQIP-Pediatric database. Multivariate regression analysis was performed using preoperative and perioperative data to determine risk factors for perioperative adverse events within 30 days of the index procedure. RESULTS: We identified 1459 patients from the NSQIP-P database for the years 2012-2014. Fifty-five percent of the patients were female. Mean age was 9.8 years (median 10 years). Median operative time was 141 min (IQR 107-181 min). Postoperative complications were noted in 5.3 % and unplanned reoperations in 3.4 % of the patients. Postoperative ventriculoperitoneal shunt placement occurred in 0.9 % of the patients. Wound problems were the most common complication (3.8 % of all patients). Univariate analysis showed the following factors were associated with perioperative adverse events: longer operative times, hospital stay >=5 days, hydrocephalus, and neurological, renal, and congenital comorbidities. On multivariate analysis, female sex (OR 1.46, 95 % CI 1.01-2.11), increased operative time (OR 1.01, 95 % CI 1.00-1.01), and hospital stay >=5 days (OR 2.62, 95 % CI 1.55-4.43) were independent factors associated with perioperative adverse events. CONCLUSION: The NSQIP-P database was used to describe surgical outcomes of posterior cranial fossa decompression in a US nationwide sample of 1459 children with Chiari type 1 malformation. The overall recorded adverse rate was low. Longer operative times and length of hospital stay >=5 days during the index admission were associated with perioperative adverse events. PMID- 27392443 TI - Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report. AB - PURPOSE: Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery. CASE PRESENTATION: A 14-year-old girl presented with mild headache. Magnetic resonance imaging (MRI) showed a small intraaxial lesion in the left thalamus, which increased in size. Stereotactic tumor biopsy was performed 2 years after the initial diagnosis, and a pathological diagnosis of diffuse astrocytoma (WHO grade 2) was made. The tumor grew further and showed contrast enhancement on MRI despite 16 months of chemotherapy. Surgical removal via the transcallosal approach was then performed, and postoperative pathological diagnosis was anaplastic astrocytoma (WHO grade 3), indicating malignant transformation of the tumor. Molecular diagnosis of tumor tissue obtained at first and second surgeries revealed H3F3A K27M mutation in both primary and secondary specimens. CONCLUSION: This report demonstrates minute neuroradiological and pathological features of malignant transformation from thalamic low grade glioma with H3F3A K27M mutation. It is noteworthy that this mutation was found in this case when the tumor was still a low-grade glioma. Tissue sampling for genetic analysis is useful in patients with thalamic gliomas to predict the clinical course and efficacy of treatments. PMID- 27392441 TI - Role of cellular events in the pathophysiology of sepsis. AB - INTRODUCTION: Sepsis is a dysregulated host immune response due to an uncontrolled infection. It is a leading cause of mortality in adult intensive care units globally. When the host immune response induced against a local infection fails to contain it locally, it progresses to sepsis, severe sepsis, septic shock and death. METHOD: Literature survey was performed on the roles of different innate and adaptive immune cells in the development and progression of sepsis. Additionally, the effects of septic changes on reprogramming of different immune cells were also summarized to prepare the manuscript. FINDINGS: Scientific evidences to date suggest that the loss of balance between inflammatory and anti inflammatory responses results in reprogramming of immune cell activities that lead to irreversible tissue damaging events and multi-organ failure during sepsis. Many surface receptors expressed on immune cells at various stages of sepsis have been suggested as biomarkers for sepsis diagnosis. Various immunomodulatory therapeutics, which could improve the functions of immune cells during sepsis, were shown to restore immunological homeostasis and improve survival in animal models of sepsis. CONCLUSION: In-depth and comprehensive knowledge on the immune cell activities and their correlation with severity of sepsis will help clinicians and scientists to design effective immunomodulatory therapeutics for treating sepsis. PMID- 27392444 TI - The incidence of severe intraventricular hemorrhage based on retrospective analysis of 35939 full-term newborns-report of two cases and review of literature. AB - INTRODUCTION: Intraventricular hemorrhage (IVH) is mostly documented in premature infants, and the younger the gestational age, the more often it occurs. IVH is very rarely reported in full-term neonates. CASE REPORT: Retrospective analysis was performed in 35939 full-term neonates, who were born in the Clinical Hospital of Gynecology and Obstetrics at the University of Medical Sciences in Poznan. Clinical data were retrieved from their medical records. We report a case series of 2 term newborns, who developed severe IVH grade 3 and 4 with no evidence of asphyxia, neuroinfection, TORCH infections, coagulation disorders and trombocytopenia, metabolic disorders, arteriovenous malformations, and selected genetic abnormalities (factor V Leiden 1601G > A polymorphism and MTHFR 677C > T; 1298A > C polymorphisms). IVH in both cases was complicated by posthemorrhagic hydrocephalus treated with decompressive lumbar punctures and next ventriculoperitoneal shunt placement. CONCLUSIONS: In conclusion, several factors influence the predisposition for severe IVH in term neonates. Perinatal period complicated by fetal distress, birth trauma, and severe asphyxia should be taken into account. However, it is possible that etiopathogenesis cannot be defined clearly as in our cases. Cranial ultrasounds in a specific group of term newborns (taking into account risk factors for IVH) should be widely recommended. PMID- 27392445 TI - Chandrashekhar Deopujari : An Introduction. PMID- 27392446 TI - Supratentorial "vascular" variant of ependymoma: a lesser known morphologic variant and a diagnostic pitfall. PMID- 27392447 TI - One-stage posterior focus debridement, interbody grafts, and posterior instrumentation and fusion in the surgical treatment of thoracolumbar spinal tuberculosis with kyphosis in children: a preliminary report. AB - PURPOSE: The purpose of this study was to determine the efficacy and feasibility of surgical management of children with thoracolumbar spine tuberculosis with kyphosis by using one-stage posterior focus debridement, interbody grafts, and posterior instrumentation and fusion. METHODS: From October 2010 to September 2013, 21 children with thoracolumbar spinal tuberculosis accompanied by kyphosis were treated with one-stage posterior decompression, interbody grafts, and posterior instrumentation and fusion. There were 13 males and 8 females, aged from 7 to 13 years old (average age 9.9 years). The mean follow-up was 34 months (range26-48 months). Patients were evaluated before and after surgery in terms of ESR, neurologic status, pain, and kyphotic angle. RESULTS: Spinal tuberculosis was completely cured, and the grafted bones were fused in all 21 patients. There was no recurrent tuberculous infection. ESR got normal within 3 months in all patients. The ASIA neurologic classification improved in all cases. Pain relief was obtained in all patients. The average preoperative kyphosis was 29.7 degrees (range 12-42 degrees ) and decreased to 5.5 degrees (range 2-10 degrees ), postoperatively. There was no significant loss of the correction at the latest follow-up. CONCLUSIONS: Our results show that one-stage posterior decompression, interbody grafts, and posterior instrumentation and fusion were an effective treatment for children with thoracolumbar spinal tuberculosis. It is characterized as minimum surgical trauma, good neurologic recovery, good correction of kyphosis, and prevention of progressive kyphosis. PMID- 27392449 TI - Induced calcium carbonate precipitation using Bacillus species. AB - Microbially induced calcium carbonate precipitation is an emerging process for the production of self-healing concrete. This study was aimed to investigate the effects and optimum conditions on calcium carbonate biosynthesis. Bacillus licheniformis, Bacillus sphaericus, yeast extract, urea, calcium chloride and aeration were found to be the most significant factors affecting the biomineralization of calcium carbonate. It was noticed that the morphology of microbial calcium carbonate was mainly affected by the genera of bacteria (cell surface properties), the viscosity of the media and the type of electron acceptors (Ca2+). The maximum calcium carbonate concentration of 33.78 g/L was achieved at the optimum conditions This value is the highest concentration reported in the literature. PMID- 27392448 TI - Pediatric symptomatic Rathke cleft cyst compared with cystic craniopharyngioma. AB - INTRODUCTION: Symptomatic Rathke cleft cysts (RCCs) are rarely detected in neuroradiological screening and are less commonly found in children than in adults. However, when RCCs are observed in children, it is important to carefully distinguish a RCC from a cystic craniopharyngioma (CP) even if surgically treated or conservatively followed up. METHODS: We conducted a retrospective review of clinical data from 11 patients with symptomatic RCCs whose ages were under 18 years and compared the data with data from 15 age- and sex-matched patients with cystic CP who were treated at our institute. RESULTS: The mean age of the patients with RCCs was 12.2 years (range, 6-18). There were six males and five females. As initial symptoms, nine patients presented with headache, while two each had impaired visual function, diabetes insipidus, and activity loss. The 14 patients with CP suffered from impaired visual function. Magnetic resonance imaging (MRI) mainly showed hyperintensity on T1-weighted images (WIs) and hypointensity on T2-WI in patients with RCC. However, patients with CP had characteristic hyperintensity on T2-WI. The average maximum diameter of the RCCs was 19.0 mm on average (range, 8-33 mm). The RCCs were thus significantly smaller than CPs (34.9 mm; range, 21-54 mm). The RCCs were usually oval or dumbbell shaped and regular in appearance, while the larger CPs were lobular and irregular. A preoperative endocrinological evaluation revealed insufficiencies in four axes in five patients with RCC. Postoperative endocrinological status improved in three patients, remained unchanged in three, and worsened in one. The gonadotropin axis was damaged in a majority (nine) of the patients with CP preoperatively. Postoperative evaluation revealed deficits in five axes in 14 patients with CP, which is a significantly different trend than observed in patients with RCC. Eight patients underwent surgical procedures (transsphenoidal surgery (TSS) in four, craniotomy in four). Two of these patients experienced a recurrence of the cysts. One of these patients subsequently underwent two craniotomies followed by radiation and other underwent TSS. Among the three conservatively treated patients, two experienced a transient worsening of their symptoms along with cyst enlargement. However, none of the three conservatively treated patients required an operation. CONCLUSIONS: When RCCs become symptomatic in children, the most common symptom they lead to is headache. The cysts are commonly small, regular, and oval in shape. Hypointensity of cyst contents on MRI is a characteristic of RCCs, which distinguishes them from CPs. Surgical intervention can be effective and lead to the relief of symptoms without a high rate of complications. However, there seems to be a relatively high recurrence rate following surgery. Thus, if the patient's symptoms remain minor, the surgical treatment option should be used only when prudent, as the patient's symptoms may improve over time. PMID- 27392450 TI - [Evidence-based trauma and orthopedic surgery : 20 years after Sackett]. AB - The article "Evidence based medicine: what it is and what it isn't" published in the BMJ in 1996, is regarded as the foundation of the evidence-based medicine (EbM) movement. Approximately 5 years later David L. Sackett, one of the leaders of the movement, requested all experts to voluntarily abandon their position to make way for young researchers and fresh ideas. Since the term was first coined and the establishment of organizations and platforms fostering the idea, EbM has polarized clinicians and scientists around the world. Clinical and methodological developments during recent years have, however, overtaken the original principles of EbM. This review highlights the core concepts of EbM which have remained unchanged and valid for the current practice of trauma and orthopedic surgery and where revision is needed. PMID- 27392451 TI - [Internal circular arc osteosynthesis of tibiotalocalcaneal arthrodesis]. AB - Tibiotalocalcaneal arthrodesis has recently become more popular as a form of reconstructive surgery. The precise anatomical orientation and the functional extrinsic musculature of the hindfoot are essential for a satisfactory result. Fixation of the arthrodesis is a mechanical problem. Straight and angulated nails are not anatomically or mechanically ideal. A circular arc nail can fix the tibia, the talus and the calcaneus in anatomical alignment. This is a pure "bone nail", in contrast to the "intramedullary nail," which is driven through an existing opening in long bones. The nail is driven through a circular arc-shaped opening in the bone, which results in optimal form-fit between nail and bone. A corresponding aiming device permits the precise shaping of the bone tunnel, which follows the orientation of the bone trabeculae. The instrumentation was applied in 11 cases, with the following indications: post-traumatic conditions, congenital deformities, chronic polyarthritis and diabetic Charcot arthropathy. The desired alignment of the hindfoot is not affected while the nail is being introduced. The fixation achieves primary stability thus allowing for early functional treatment. PMID- 27392452 TI - Critical distance between the cartilaginous Eustachian tube and the internal carotid artery. AB - During the last decade, endoscopic surgery of the Eustachian tube (ET) has been advocated for ET dilatory dysfunction and for patulous ET. The internal carotid artery (ICA) and the ET are closely related, and knowledge of their surgical anatomy has become essential. This study was designed to establish the anatomical relationships between the endoscopically critical area along the full length of the cartilaginous ET and its closest association with the ICA. The perpendicular distance between the ET lumen and the ICA was measured from head magnetic resonance images (MRI) at three levels: (A) cartilaginous and bony ET junctional point, (B) mid cartilaginous ET point, and (C) the nasopharyngeal orifice of the cartilaginous ET. Totally, 200 sides were reviewed in MRI scans of 229 patients. The mean distances for each level were: A = 4.3 mm (range 1.6-10.4 mm), B = 25 mm (range 9.0-61.6 mm), and C = 62 mm (range 34.3-84.4 mm). The perpendicular distance between ET and ICA at the nasopharyngeal orifice is large, but the distance shortens quickly while moving from the nasopharyngeal orifice of the ET to the junctional point of the ET. The potential for complications to the ICA rises as the surgical field moves closer to the isthmus of the ET because of the decreasing distance between the ET and the ICA. PMID- 27392453 TI - Breastfeeding Recommendations for Women Who Receive Medication-Assisted Treatment for Opioid Use Disorders: AWHONN Practice Brief Number 4. PMID- 27392454 TI - The reduced flavin-dependent monooxygenase SfnG converts dimethylsulfone to methanesulfinate. AB - The biochemical pathway through which sulfur may be assimilated from dimethylsulfide (DMS) is proposed to proceed via oxidation of DMS to dimethylsulfoxide (DMSO) and subsequent conversion of DMSO to dimethylsulfone (DMSO2). Analogous chemical oxidation processes involving biogenic DMS in the atmosphere result in the deposition of DMSO2 into the terrestrial environment. Elucidating the enzymatic pathways that involve DMSO2 contribute to our understanding of the global sulfur cycle. Dimethylsulfone monooxygenase SfnG and flavin mononucleotide (FMN) reductase MsuE from the genome of the aerobic soil bacterium Pseudomonas fluorescens Pf0-1 were produced in Escherichia coli, purified, and biochemically characterized. The enzyme MsuE functions as a reduced nicotinamide adenine dinucleotide (NADH)-dependent FMN reductase with apparent steady state kinetic parameters of Km = 69 MUM and kcat/Km = 9 min(-1) MUM (-1) using NADH as the variable substrate, and Km = 8 MUM and kcat/Km = 105 min(-1) MUM (-1) using FMN as the variable substrate. The enzyme SfnG functions as a flavoprotein monooxygenase and converts DMSO2 to methanesulfinate in the presence of FMN, NADH, and MsuE, as evidenced by (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy. The results suggest that methanesulfinate is a biochemical intermediate in sulfur assimilation. PMID- 27392455 TI - Insight into cognitive decline from Zn2+ dynamics through extracellular signaling of glutamate and glucocorticoids. AB - Glutamatergic neuron activity and/or the modification of the activity with glucocorticoids are closely linked to synaptic Zn2+ dynamics as well as synaptic Ca2+ dynamics. The dynamic crosstalk of synaptic Zn2+ signaling to intracellular Ca2+ signaling via calcium channels is involved in synaptic plasticity such as long-term potentiation (LTP) and cognitive activity. The influx of extracellular Zn2+ into postsynaptic neurons, which is closely linked to glutamate signaling in the synaptic cleft, is critical for cognitive activity. However, excess intracellular Zn2+ signaling induced by excess glutamatergic neuron activity is involved in not only cognitive decline in neurological disorders but also stress induced cognitive decline. On the other hand, it has been recognized that excess Ca2+ influx into postsynaptic neurons induces neuronal death, while the involvement of excess intracellular Ca2+ signaling in cognitive decline is poorly understood. Understanding of synaptic Zn2+ dynamics, which are modified by glutamate and glucocorticoid signaling, may be meaningful to prevent Zn2+ mediated cognitive decline. This paper summarizes the current knowledge on Zn2+ dynamics under changing synaptic environment and its impact on cognitive decline. PMID- 27392456 TI - Lysyl-tRNA synthetase from Myxococcus xanthus catalyzes the formation of diadenosine penta- and hexaphosphates from adenosine tetraphosphate. AB - Myxococcus xanthus lysyl-tRNA synthetase (LysS) produces diadenosine tetraphosphate (Ap4A) from ATP in the presence of Mn(2+); in the present study, it also generated Ap4 from ATP and triphosphate. When ATP and Ap4 were incubated with LysS and pyrophosphatase, first Ap4A, Ap5A, and ADP, and then Ap5, Ap6A, and Ap3A were generated. The results suggest that in the first step, LysS can form lysyl-AMP and lysyl-ADP intermediates from Ap4 and release triphosphate and diphosphate, respectively, whereas in the second step, it can produce Ap5 from lysyl-ADP with triphosphate, and Ap6A from lysyl-ADP with Ap4. In addition, in the presence of Ap4 and pyrophosphatase, but absence of ATP, LysS also generates diadenosine oligophosphates (ApnAs: n = 3-6). These results indicate that LysS has the ability to catalyze the formation of various ApnAs from Ap4 in the presence of pyrophosphatase. Furthermore, the formation of Ap4A by LysS was inhibited by tRNA(Lys) in the presence of 1 mM ATP. To the best of our knowledge, this is the first report of Ap5A and Ap6A synthesis by lysyl-tRNA synthetase. PMID- 27392457 TI - [Not Available]. PMID- 27392458 TI - [Not Available]. PMID- 27392459 TI - [Not Available]. PMID- 27392460 TI - [Not Available]. PMID- 27392461 TI - [Not Available]. PMID- 27392462 TI - Chemokine, cytokine and type I interferon production induced by Toll-like receptor activation in common variable immune deficiency. AB - Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency and is associated with recurrent infections and chronic inflammatory diseases. We evaluated the ability of Toll-like receptor (TLR) ligands to induce secretion of chemokines, cytokines and type I interferons by peripheral blood mononuclear cells (PBMCs) from CVID patients. High levels of CXCL10, CCL2, CXCL9, CCL5, CXCL8, and IL-6 were detected in sera of CVID patients compared with healthy controls. Increased chemokine levels were observed in unstimulated PBMCs, but after stimulation with TLR2 and TLR4 agonists, equivalent chemokine and pro-inflammatory cytokine secretion, as in healthy controls, was observed, whereas TLR4 agonist induced a decreased secretion of CCL2 and CXCL8 and increased secretion of TNF. Decreased IFN-alpha secretion induced by TLR7/TLR8 activation was observed in CVID, which was recovered with TLR9 signaling. Our findings revealed that TLR9 activation has an adjuvant effect on the altered type I response in CVID. PMID- 27392464 TI - Resistant or Sensitive: Time is of the Essence. PMID- 27392463 TI - Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis. AB - Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP 1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC). We estimated serum levels of CCL2 and CXCL12 in patients with SLE (n=99) and compared the results with healthy individuals (n=21). In order to prove our hypothesis we used l-enantiomeric RNA Spiegelmer(r) chemokine antagonists, i.e. the CCL2-specific mNOX-E36 and the CXCL12-specific NOX-A12 to treat female MRL/lpr mice from week 12 to 20 of age with either anti-CXCL12 or anti-CCL2 alone or both. SLE patients showed elevated serum levels of CCL2 but not of CXCL12. Female MRL/lpr mice treated with dual blockade showed significantly more effective than either monotherapy in preventing proteinuria, immune complex glomerulonephritis, and renal excretory failure and the results are at par with CYC treatment. Dual blockade reduced leukocyte counts and renal IL-6, IL-12p40, CCL-5, CCL-2 and CCR-2 mRNA expression. Dual blockade of CCL2 and CXCL12 can be as potent as CYC to suppress the progression of proliferative lupus nephritis probably because the respective chemokine targets mediate different disease pathomechanisms, i.e. systemic autoimmunity and peripheral tissue inflammation. PMID- 27392465 TI - Brain potential changes in voluntary and passive movements in humans: readiness potential and reafferent potentials. AB - A method of chronological data storage and reverse computation is described by which bio-electrical phenomena preceding 'spontaneous' events within the nervous system can be analysed if these events appear repeatedly and are capable of triggering a computer.Slow brain potentials accompanying voluntary and passive movements of the limbs were analysed by this method. These potentials were recorded from different points of the scalp from 12 healthy subjects in 94 experiments with more than 100 movements in each record. At times artifacts were superimposed upon cerebral potentials. The former were identified, and, as far as possible, eliminated.Voluntary hand or foot movements are preceded by a slowly increasing surface-negative cortical potential of 10-15 MUV, called readiness potential. This potential is maximal over the contralateral precentral region, but shows bilateral spread and is larger over the frontal than over the occipital areas. The readiness potential increases with intentional engagement and is reduced by mental indifference of the subject.Voluntary movements are followed by a complex potential with an early positive phase that begins 30-90 msec after the onset of movement. The late potentials following voluntary movements are similar to those after passive movements. Both resemble the late bilateral components of the evoked potentials after electrical stimulation of peripheral nerves. Some variable differences between the early components of the potentials after the onset of active and passive movements require further investigation.No relation between the onset of voluntary movements and the phase of the alpha rhythm could be detected.Further applications of reverse computation are addressed. Similarities between the readiness potential and G. WALTER'S expectancy wave in conditioned reflexes, and the sources of artifacts through eye movements etc. are discussed. PMID- 27392466 TI - Evaluation of three risk assessment tools in discriminating fracture status among Chinese patients undergoing hemodialysis. AB - : We evaluated three risk assessment tools, including bone mineral density (BMD) measurement by dual energy X-ray absorptiometry (DXA), osteoporosis self assessment tool for Asians (OSTA), and fracture risk assessment tool (FRAX), for the prediction of fracture status among Chinese patients undergoing hemodialysis. All of the three assessment tools have a reasonable capability in discriminating fractures. INTRODUCTION: Fractures are common in hemodialysis patients however insufficiently assessed. Our study aimed to assess the ability of three widely used tools [BMD, OSTA, and FRAX] to discriminate fracture status in patients with renal failure undergoing hemodialysis. METHODS: We enrolled 136 hemodialysis patients in a tertiary teaching hospital setting. BMD was measured using DXA at the lumbar spine and the hip region. OSTA was calculated from weight and age. FRAX score was calculated based upon online availability. Discriminative abilities of BMD, OSTA, and FRAX in fracture status were analyzed by receiver operator characteristic (ROC) curves. RESULTS: There were total 16 fractures (11.76 %) identified in 136 hemodialysis patients. BMD at any site (lumbar spine L1-L4, femoral neck, and total hip) was independently associated with fracture. Areas under the curves (AUC) of BMD (lumbar spine L1-L4, femoral neck, total hip), OSTA, FRAX1 (non-BMD model), and FRAX2 (BMD model) were 0.669 (95 % CI 0.583, 0.747), 0.708 ( 95 % CI 0.624, 0.783), 0.736 (95 % CI 0.654, 0.808), 0.686 (95 % CI 0.601, 0.763), 0.715 (95 % CI 0.631, 0.789), and 0.697 (95 % CI 0.613, 0.773), respectively. The differences of their performance were not significant. CONCLUSIONS: All of the three risk assessment tools had the ability to discriminate fracture status among hemodialysis patients; FRAX BMD model did not improve the discriminative ability of BMD or FRAX non-BMD model alone. PMID- 27392467 TI - Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa. AB - : We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA. INTRODUCTION: Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN. METHODS: Seventy females (age 15.5 +/- 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures. RESULTS: Trabecular vBMD Z-scores were lower in AN compared to controls (AN -0.31 +/- 1.42 vs +0.11 +/- 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 +/- 0.92 vs -0.50 +/- 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57 0.82, p < 0.001). Markers of nutritional status positively correlated with Z scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all). CONCLUSIONS: This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study. PMID- 27392468 TI - Editorial Comment. PMID- 27392469 TI - Editorial Comment. PMID- 27392470 TI - Editorial Comment. PMID- 27392471 TI - Editorial Comment. PMID- 27392472 TI - Editorial Comment. PMID- 27392473 TI - Reply by Authors. PMID- 27392474 TI - Editorial Comment. PMID- 27392475 TI - Re: The NLRP3 Inflammasome Mediates Inflammation Produced by Bladder Outlet Obstruction: F. M. Hughes, Jr., H. M. Hill, C. M. Wood, A. T. Edmondson, A. Dumas, W. C. Foo, J. M. Oelsen, G. Rac and J. T. Purves J Urol 2016;195:1598 1605. PMID- 27392476 TI - Follicle-Stimulating Hormone Receptor (FSHR): A Promising Tool in Oncology? AB - The cellular pathway of follicle-stimulating hormone (FSH) and its receptor (FSHR) is typically involved in reproduction in mammals. In humans, the FSHR is normally found in cells of the testis and the ovary, while it is scarcely expressed in other normal tissues. The expression of FSH/FSHR is studied in prostate, thyroid, and ovarian cancer tissues. Recently, the expression of FSHR was uniformly documented in malignant vascular endothelial cells from different tumor types, while in normal or inflammatory tissues its expression was scarce, suggesting a potential role of a pan-receptor in cancer. Subsequent studies have attempted to verify this unique specificity of this molecule and further define its features in malignant microenvironments but have had conflicting results, mostly because of differing techniques and immaturity of antibodies. Still, the lack of FSHR expression in most non-cancerous cells, in contrast to its specific correlation with the malignant tissue microenvironment, implies a potential role as both a diagnostic and a therapeutic tool. FSHR might also have a very specific role in malignancies, such as angiogenic and/or growth factor malignancies, but this is yet to be validated. Moreover, the expression of FSHR in endothelial malignant cells could have a predictive impact on disease progression, especially in relation to therapies targeting the tumor vasculature. In this review we look deep into the physiology of the FSH/FSHR pathway and evaluate the potential of FSHR as a predictive and prognostic tool in oncology. PMID- 27392478 TI - Effect of Shuwei Decoction () on rats with functional dyspepsia. AB - OBJECTIVE: To investigate the effects of Shuwei Decoction (, SWD) on gastric emptying, serum stem cell factor (SCF), the content of serum nitric oxide (NO), and structure change of interstitial cells of Cajal (ICC) in functional dyspepsia (FD) rats. METHODS: Sixty Sprague Dawley rats were randomly divided into 6 groups: blank group (group A), model group (group B), mosapride group (group C), Muxiang Shunqi Pill (, MSP) group (group D), SWD low-dose group (group E), and SWD high-dose group (group F), 10 rats in each group. FD rat model was established by clasping rats' tails for 7 days, except the group A. After 3 days, group A and group B were given distilled water, and the medicated rats were given corresponding medicine for 14 days. The gastric emptying, structure change of ICC in gastric antrum by transmission electron microscope, the content of serum NO by nitrate reductant and SCF by enzyme linked immunosorbent assay were observed. RESULTS: Compared with group A, the rats in group B delayed gastric emptying, serum SCF decreased, serum NO increased (P <0.05). Compared with group B, the rats in groups D, E and F were improved on gastric emptying, obviously increased on serum SCF, decreased on serum NO (P <0.05), and structure change of ICC in gastric antrum improved. Compared with group B, structure change of ICC of group E after treatment was improved and was closed to group A. CONCLUSION: SWD recovered gastrointestinal motility of FD, possibly by regulating the levels of serum NO and SCF, and improving the structure of ICC in gastric antrum. PMID- 27392477 TI - Race-based medical mistrust, medication beliefs and HIV treatment adherence: test of a mediation model in people living with HIV/AIDS. AB - Race-based medical mistrust significantly predicts non-adherence to antiretroviral therapy (ART) in people living with HIV. The current study builds on previous research that shows beliefs about medication necessity (i.e., "My medicines protect me from becoming worse") and concerns (i.e., "Having to take my medicines worries me") mediate the association between race-based medical mistrust and medication adherence. Racial and ethnic minority men and women living with HIV and receiving ART (N = 178) in a southern US city completed computerized measures of demographic and health characteristics, telephone interviews of race-based medical mistrust and medication beliefs, and unannounced phone-based pill counts for ART adherence. Multiple mediation modeling showed that medical mistrust is related to medication necessity and concerns beliefs and ART adherence. Furthermore, medication necessity beliefs predicted ART adherence. The indirect effect of medical mistrust on adherence through medication necessity beliefs was also significant. Results confirm that medication necessity beliefs, although not concerns beliefs, mediate the association between medical mistrust and ART adherence. Medication necessity beliefs offer a viable target for interventions to improve ART adherence in the context of mistrust that patients may have for medical providers and health care systems. PMID- 27392479 TI - Neuroprotective effects of Tongmai Yizhi Decoction () against Alzheimer's disease through attenuating cyclin-dependent kinase-5 expression. AB - OBJECTIVES: To explore the protective effects of Tongmai Yizhi Decoction (, TYD), a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1-40 (Abeta1-40) peptide and ibotenic (IBO) induced Alzheimer's disease (AD) model rats. METHODS: The in vivo model was established by injecting Abeta1-40 and IBO into left hippocampal CA1 area of Sprague-Dawley (SD) rat to mimic AD. Totally 32 SD rats were divided into 4 groups, including sham operation group, AD model group, TYD group [AD rats treated with TYD at the dosage of 19.44 g/(kg*d) for 4 weeks] and huperzine A group [AD rats treated with huperzine A at the dosage of 40.5 MUg/(kg*d) for 4 weeks]. Spatial learning and memory level was detected by Morris Water Maze test. Histological morphology in the hippocampus was tested by hematoxylin-eosin (HE) staining. Cyclin-dependent kinase-5 (Cdk5) protein and gene expression level were investigated by Western blot analysis and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. RESULTS: Abeta1-40 and IBO treatment induced longer escape latency of rats, compared with sham operation group from day 25 (P<0.01). However, TYD and huperzine A obviously shortened the escape latency from day 26 (P<0.01). Moreover, the effect of TYD was similar to huperzine A (P>0.05). Furthermore, HE staining also showed that TYD and huperzine A reversed the neuropathological changes in the hippocampus triggered by Abeta1-40 and IBO. TYD and huperzine A effectively reduced the expression levels of Cdk5 protein and gene located in rat hippocampus, compared with the AD model group (P<0.01). CONCLUSION: TYD could be a promising neuroprotective agent for protecting neuron from AD injury through inhibiting Cdk5 expression. PMID- 27392480 TI - Huoxue Anxin Recipe () promotes myocardium angiogenesis of acute myocardial infarction rats by up-regulating miR-210 and vascular endothelial growth factor. AB - OBJECTIVE: To investigate the microRNAs (miRNAs) expression profile of acute myocardial infarction (AMI) rats and the regulating effects of Huoxue Anxin Recipe (, HAR) on angiogenesis-related miRNAs and genes. METHODS: Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups (15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miRNAs expression profile was detected by quantitative realtime polymerase chain reaction (qRT-PCR). The mRNA and protein expressions of vascular endothelial growth factor (VEGF), and a target gene of miR-210 was further detected by qRT-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. RESULTS: Compared with the sham group, ejection fraction (EF) and fractional shortening (FS) values were decreased significantly in the AMI group (P<0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly (P<0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miRNAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miRNAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mRNA and protein expressions of VEGF were decreased significantly in the AMI group (P<0.05 vs. sham group), and increased significantly in the AMI+HAR group (P<0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group (P<0.05 vs. sham group), and increased significantly in the AMI+HAR group (P<0.01 vs. AMI group). CONCLUSIONS: HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF. PMID- 27392481 TI - Effect of integrated Chinese and Western medicine therapy on severe hand, foot and mouth disease: A prospective, randomized, controlled trial. AB - OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) plus Western medicine (WM) in the treatment of pediatric patients with severe hand, foot and mouth disease (HFMD) by conducting a prospective, controlled, and randomized trial. METHODS: A total of 451 pediatric patients with severe HFMD were randomly assigned to receive WM therapy alone (224 cases, WM therapy group) or CM [Reduning Injection ( ) or Xiyanping Injection ()] plus WM therapy (227 cases, CM plus WM therapy group) for 7-10 days, according to a web-based randomization system. The primary outcome was fever clearance time, which was presented as temperature decreased half-life time. The secondary outcomes included the rate of rash/herpes disappearance within 120 h, as well as the rate for cough, runny nose, lethargy and weakness, agitation or irritability, and vomiting clearance within 120 h. The drug-related adverse events were also recorded. RESULTS: The temperature decreased half-life time was 40.4 h in the WM therapy group, significantly longer than 27.2 h in the CM plus WM therapy group (P<0.01). Moreover, the rate for rash/herpes disappearance within 120 h was 43.6% (99/227) in the CM plus WM therapy group, significantly higher than 29.5% (66/224) in the WM therapy group (P<0.01). In addition, the rate for cough, lethargy and weakness, agitation or irritability disappearance within 120 h was 32.6% (74/227) in the CM plus WM therapy group, significantly higher than 19.2% (43/224) in the WM therapy group (P<0.01). No drug-related adverse events were observed during the course of the study. CONCLUSION: The combined CM and WM therapy achieved a better therapeutic efficacy in treating severe HFMD than the WM therapy alone. Reduning or Xiyanping Injections may become an important complementary therapy to WM for relieving the symptoms of severe HFMD. (Registration No. NCT01145664). PMID- 27392482 TI - Ablation of BAF170 in Developing and Postnatal Dentate Gyrus Affects Neural Stem Cell Proliferation, Differentiation, and Learning. AB - The BAF chromatin remodeling complex plays an essential role in brain development. However its function in postnatal neurogenesis in hippocampus is still unknown. Here, we show that in postnatal dentate gyrus (DG), the BAF170 subunit of the complex is expressed in radial glial-like (RGL) progenitors and in cell types involved in subsequent steps of adult neurogenesis including mature astrocytes. Conditional deletion of BAF170 during cortical late neurogenesis as well as during adult brain neurogenesis depletes the pool of RGL cells in DG, and promotes terminal astrocyte differentiation. These derangements are accompanied by distinct behavioral deficits, as reflected by an impaired accuracy of place responding in the Morris water maze test, during both hidden platform as well as reversal learning. Inducible deletion of BAF170 in DG during adult brain neurogenesis resulted in mild spatial learning deficits, having a more pronounced effect on spatial learning during the reversal test. These findings demonstrate involvement of BAF170-dependent chromatin remodeling in hippocampal neurogenesis and cognition and suggest a specific role of adult neurogenesis in DG in adaptive behavior. PMID- 27392483 TI - Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor for anti hepatitis C treatment. AB - Recently, direct antiviral agents against hepatitis C virus (HCV) infection have been developed as highly effective anti-HCV drugs. However, the appearance of resistant viruses against direct anti-viral agents is an unsolved problem. One of the strategies considered to suppress the emergence of the drug-resistant viruses is to use drugs inhibiting the host factor, which contributes to HCV proliferation, in combination with direct anti-viral agents. The replication complex was reported to be present in the membranous compartment in the cells. Thus, lipid metabolism modulators are good candidates to regulate virus assembly and HCV replication. Recent studies have shown that stearoyl-CoA desaturase (SCD), an enzyme for long-chain mono-unsaturated fatty acid (LCMUFA) synthesis, is a key factor that defines HCV replication efficiency. Systemic exposure to SCD 1 inhibor induces some side effects in the eyes and skin. Thus, systemic SCD-1 inhibitors are considered inappropriate for HCV therapy. To avoid the side effects of systemic SCD-1 inhibitors, the liver-specific SCD-1 inhibitor, MK8245, was synthesized; it showed antidiabetic effects in diabetic model mice with no side effects. In the phase 1 clinical study on measurement of MK8245 tolerability, no significant side effects were reported (ClinicalTrials.gov Identifier: NCT00790556). Therefore, we thought liver-specific SCD-1 inhibitors would be suitable agents for HCV-infected patients. MK8245 was evaluated using recombinant HCV culture systems. Considering current HCV treatments, to avoid the emergence of direct anti-viral agents-resistant viruses, combination therapy with direct anti-viral agents and host-targeted agents would be optimal. With this viewpoint, we confirmed MK8245's additive or synergistic anti-HCV effects on current direct anti-viral agents and interferon-alpha therapy. The results suggest that MK8245 is an option for anti-HCV multi-drug therapy with a low risk of emergence of drug-resistant HCV without significant side effects. PMID- 27392484 TI - From the Secretary General of EACA. PMID- 27392485 TI - From the Congress Presidency. PMID- 27392486 TI - Scientific program. PMID- 27392487 TI - List of posters. PMID- 27392488 TI - Opening lectures. PMID- 27392490 TI - Symposium presentations. PMID- 27392495 TI - Maternal obesity and prenatal programming. AB - Obesity is a significant and increasing public health concern in the United States and worldwide. Clinical and epidemiological evidence clearly shows that genetic and environmental factors contribute to the increased susceptibility of humans to obesity and its associated comorbidities; the interplay of these factors is explained by the concept of epigenetics. The impact of maternal obesity goes beyond the newborn period; fetal programming during the critical window of pregnancy, can have long term detrimental effects on the offspring as well as future generations. Emerging evidence is uncovering a link between the clinical and molecular findings in the offspring with epigenetic changes in the setting of maternal obesity. Research targeted towards reducing the transgenerational propagation and developmental programming of obesity is vital in reducing the increasing rates of disease. PMID- 27392494 TI - Ghrelin acts as energy status sensor of male reproduction by modulating Sertoli cells glycolytic metabolism and mitochondrial bioenergetics. AB - Ghrelin is a growth hormone-releasing peptide that has been suggested to interfere with spermatogenesis, though the underling mechanisms remain unknown. We studied the effect of ghrelin in human Sertoli cells (hSCs) metabolic phenotype. For that, hSCs were exposed to increasing concentrations of ghrelin (20, 100 and 500 pM) mimicking the levels reported in obese, normal weight, and severely undernourished individuals. The metabolite production/consumption was determined. The protein levels of key glycolysis-related transporters and enzymes were assessed. The lactate dehydrogenase (LDH) activity was measured. Mitochondrial complexes protein levels and mitochondria membrane potential were also measured. We showed that hSCs express the growth hormone secretagogue receptor. At the concentration present in the plasma of normal weight men, ghrelin caused a decrease of glucose consumption and mitochondrial membrane potential in hSCs, though LDH activity and lactate production remained unchanged, illustrating an alteration of glycolytic flux efficiency. Exposure of hSCs to levels of ghrelin found in the plasma of severely undernourished individuals decreased pyruvate consumption and mitochondrial complex III protein expression. All concentrations of ghrelin decreased alanine and acetate production by hSCs. Notably, the effects of ghrelin levels found in severely undernourished individuals were more pronounced in hSCs metabolic phenotype highlighting the importance of a proper eating behavior to maintain male reproductive potential. In conclusion, ghrelin acts as an energy status sensor for hSCs in a dose dependent manner, showing an inverse association with the production of lactate, thus controlling the nutritional support of spermatogenesis. PMID- 27392493 TI - Continuous crossbreeding of sake yeasts using growth selection systems for a-type and alpha-type cells. AB - Sake yeasts belong to the budding yeast species Saccharomyces cerevisiae and have high fermentation activity and ethanol production. Although the traditional crossbreeding of sake yeasts is a time-consuming and inefficient process due to the low sporulation rates and spore viability of these strains, considerable effort has been devoted to the development of hybrid strains with superior brewing characteristics. In the present work, we describe a growth selection system for a- and alpha-type cells aimed at the crossbreeding of industrial yeasts, and performed hybridizations with sake yeast strains Kyokai No. 6, No. 7 and No. 9 to examine the feasibility of this approach. We successfully generated both a- and alpha-type strains from all parental strains, and acquired six types of hybrids by outcrossing. One of these hybrid strains was subjected to continuous crossbreeding, yielding the multi-hybrid strain, which inherited the genetic characteristics of Kyokai No. 6, No. 7 and No. 9. Notably, because all of the genetic modifications of the yeast cells were introduced using plasmids, these traits can be easily removed. The approach described here has the potential to markedly accelerate the crossbreeding of industrial yeast strains with desirable properties. PMID- 27392496 TI - Connective tissue growth factor mediates growth differentiation factor 8-induced increase of lysyl oxidase activity in human granulosa-lutein cells. AB - Lysyl oxidase (LOX) is an essential enzyme for the stabilization of the extracellular matrix (ECM) and the subsequent follicle and oocyte maturation. Currently, there is limited information pertaining to the regulation of LOX activity in human ovarian tissue. Growth differentiation factor 8 (GDF8) is a unique member of the transforming growth factor-beta superfamily that is expressed in human granulosa cells and has important roles in regulating a variety of ovarian functions. The aim of the present study was to investigate the effects of GDF8 on the regulation of LOX expression and activity in human granulosa cells and to examine the underlying molecular determinants. An established immortalized human granulosa cell line (SVOG) and primary granulosa lutein cells were used as study models. Using dual inhibition approaches (TGF beta type I inhibitor SB505124 and small interfering RNAs) and ChIP analyses, we have demonstrated that GDF8 up-regulated the expression of connective tissue growth factor (CTGF) through the activin receptor-like kinase 5-mediated SMAD2/3 SMAD4 signaling pathways. In addition, the increase in CTGF expression contributed to the GDF8-induced increase in LOX expression and activity. Our findings suggest that GDF8 and CTGF may play critical roles in the regulation of ECM formation in human granulosa cells. PMID- 27392497 TI - Persistent influence of maternal obesity on offspring health: Mechanisms from animal models and clinical studies. AB - The consequences of excessive maternal weight and adiposity at conception for the offspring are now well recognized. Maternal obesity increases the risk of overweight and obesity even in children born with appropriate-for-gestational age (AGA) birth weights. Studies in animal models have employed both caloric excess and manipulation of macronutrients (especially high-fat) to mimic hypercaloric intake present in obesity. Findings from these studies show transmission of susceptibility to obesity, metabolic dysfunction, alterations in glucose homeostasis, hepatic steatosis, skeletal muscle metabolism and neuroendocrine changes in the offspring. This review summarizes the essential literature in this area in both experimental and clinical domains and focuses on the translatable aspects of these experimental studies. Moreover this review highlights emerging mechanisms broadly explaining maternal obesity-associated developmental programming. The roles of early developmental alterations and placental adaptations are also reviewed. Increasing evidence also points to changes in the epigenome and other emerging mechanisms such as alterations in the microbiome that may contribute to persistent changes in the offspring. Finally, we examine potential interventions that have been employed in clinical cohorts. PMID- 27392498 TI - Strategy of integrated evaluation on treatment of traditional Chinese medicine as 'interaction of system to system' and establishment of novel fuzzy target contribution recognition with herb-pairs, a case study on Astragali Radix-Fructus Corni. AB - To date, in the struggle against diseases and the development of TCM, what we lack is wisdom rather than knowledge. Studies on pharmacology of traditional Chinese medicine are facing critical challenges on how to select the proper parameters or targets to represent the pharmacological evaluation system. With seven steps of optimized modules established by ourselves, we can re-evaluate TCM in a panorama view with a proper pharmacological evaluation system. In this article, with the treatment of TCM as 'interaction of system to system', a novel and generally applicable approach called fuzzy target contribution recognition was established and agents from Astragali Radix-Fructus Corni in resisting diabetic nephropathy were successfully discovered for the first time. CG6, a promising agent from this herb-pair on the treatment of diabetic nephropathy, was finally acquired and its possible molecular mechanism was explored through a nuclear factor erythroid 2-Like 2 (NFE2L2) activation-dependent pathway. PMID- 27392499 TI - The "putative" role of transcription factors from HlWRKY family in the regulation of the final steps of prenylflavonid and bitter acids biosynthesis in hop (Humulus lupulus L.). AB - Lupulin glands localized in female hop (Humulus lupulus L.) cones are valuable source of bitter acids, essential oils and polyphenols. These compounds are used in brewing industry and are important for biomedical applications. In this study we describe the potential effect of transcription factors from WRKY family in the activation of the final steps of lupulin biosynthesis. In particular, lupulin gland-specific transcription factor HlWRKY1 that shows significant similarity to AtWRKY75, has ability to activate the set of promoters driving key genes of xanthohumol and bitter acids biosynthesis such as chalcone synthase H1, valerophenone synthase, prenyltransferase 1, 1L and 2 and O-methyltransferase-1. When combined with co-factor HlWDR1 and silencing suppressor p19, HlWRKY1 is able to enhance transient expression of gus gene driven by Omt1 and Chs_H1 promoters to significant level as compared to 35S promoter of CaMV in Nicotiana. benthamiana. Transformation of hop with dual Agrobacterium vector bearing HlWRKY1/HlWDR1 led to ectopic overexpression of these transgenes and further activation of lupulin-specific genes expression in hop leaves. It was further showed that (1) HlWRKY1 is endowed with promoter autoactivation; (2) It is regulated by post-transcriptional gene silencing (PTGS) mechanism; (3) It is stimulated by kinase co-expression. Since HlWRKY1 promotes expression of lupulin specific HlMyb3 gene therefore it can constitute a significant component in hop lupulin regulation network. Putative involvement of HlWRKY1 in the regulation of lupulin biosynthesis may suggest the original physiological function of lupulin components in hop as flower and seed protective compounds. PMID- 27392500 TI - Biosimilars from a practicing rheumatologist perspective: An overview. AB - The earliest experimental trials of monoclonal antibodies took place in the early 1980s using murine monoclonal antibodies directed at human lymphoma and leukemia cell antigens. Since those early trials, therapeutic advances have produced monoclonal antibodies and fusion proteins that are now used in multiple disease states including cancers, autoimmune diseases, inflammatory bowel disease, psoriasis, neurologic disorders and others. Modern techniques have led to the development of multiple chimeric or fully humanized immunoglobulin, receptor and fusion proteins targeting cell markers, interleukins or other target proteins involved in pathophysiologic disease processes resulting in marked improvements in many different disease states. As novel innovator patents are about to expire, commercial entities are actively involved in creating follow-on agents that are similar to these original biologic innovator compounds. The hope and promise of these "biosimilars" to society is increased access to more patients at lower costs. The desire of manufacturers is product development at lower cost (lower research and development) with great potential for widespread use and sales. The challenge for regulators and authorities is to develop strategies that do not overlook the safety concerns of physicians and patients by excessively streamlining approval processes and overlooking potential efficacy and immunologic differences compared to the original innovator compounds. PMID- 27392501 TI - Microbiota at the crossroads of autoimmunity. AB - Autoimmune diseases have a multifactorial etiology including genetic and environmental factors. Recently, there has been increased appreciation of the critical involvement of the microbiota in the pathogenesis of autoimmunity, although in many cases, the cause and the consequence are not easy to distinguish. Here, we suggest that many of the known cues affecting the function of the immune system, such as genetics, gender, pregnancy and diet, which are consequently involved in autoimmunity, exert their effects by influencing, at least in part, the microbiota composition and activity. This, in turn, modulates the immune response in a way that increases the risk for autoimmunity in predisposed individuals. We further discuss current microbiota-based therapies. PMID- 27392502 TI - Cellular analyses in the monitoring of autoimmune diseases. PMID- 27392503 TI - Systemic-onset juvenile idiopathic arthritis. AB - Systemic-onset juvenile idiopathic arthritis (SoJIA) is a systemic inflammatory disease which has up to now been classified as a category of juvenile idiopathic arthritis. However, in this context, systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that it may rather be part of the spectrum of autoinflammatory disorders. The disease is in fact unique with regard to the other JIA categories, in terms of clinical manifestations, prognosis, and response to conventional immunosuppressant therapies. It is characterized clinically by fever, lymphadenopathy, arthritis, rash, and serositis. IL-1 and IL-6 play a major role in the pathogenesis of SoJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SoJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation continue to be a major issue in patients' care. Recent advances on the pathogenesis and treatment have revolutionized the care and prognosis of this potentially life-threatening pediatric condition. PMID- 27392491 TI - Platform presentations. PMID- 27392504 TI - Revisiting the regulatory roles of the TGF-beta family of cytokines. AB - TGF-beta family members are multipotent cytokines that are involved in many cellular processes, including cell differentiation, organ development, wound healing and immune regulation. TGF-beta has pleiotropic effects on adaptive immunity, especially in the regulation of CD4(+) T cell and B cell responses. Furthermore, identification of CD4(+) T cell subsets that produce TGF-beta3 revealed unexpected roles of TGF-beta3 in the control of adaptive immunity. In contrast to TGF-beta1, which induces extensive fibrosis, TGF-beta3 induces non scarring wound healing and counteracts tissue fibrosis. Recent progress in the understanding of the activation mechanism of TGF-beta may enable us to develop novel biologic therapies based on advanced protein engineering. PMID- 27392505 TI - Autoimmunity and infection in common variable immunodeficiency (CVID). AB - Common variable immunodeficiency (CVID) is a heterogeneous group of diseases, characterized by primary hypogammaglobulinemia. B and T cell abnormalities have been described in CVID. Typical clinical features of CVID are recurrent airway infections; lymphoproliferative, autoinflammatory, or neoplastic disorders; and autoimmune diseases among which autoimmune thrombocytopenia (ITP) is the most common. The coexistence of immunodeficiency and autoimmunity appears paradoxical, since one represents a hypoimmune state and the other a hyperimmune state. Considering both innate and adaptive immune response abnormalities in CVID, it is easier to understand the mechanisms that lead to a breakdown of self-tolerance. CD21(low) B cells derive from mature B cells that have undergone chronic immune stimulation; they are increased in CVID patients. The expansion of CD21(low) B cells is also observed in certain autoimmune diseases. We have studied CD21(low) B cells in patients with CVID, CVID, and ITP and with ITP only. We observed a statistically significant increase in the CD21(low) population in the three pathological groups. Moreover, we found statistical differences between the two groups of CVID patients: patients with ITP had a higher percentage of CD21(low) cells. Our data suggest that CD21(low) cells are related to autoimmunity and may represent a link between infection and autoimmunity. PMID- 27392507 TI - Implications of Total to High-Density Lipoprotein Cholesterol Ratio Discordance With Alternative Lipid Parameters for Coronary Atheroma Progression and Cardiovascular Events. AB - The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio may quantify atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apolipoprotein B (apoB). We analyzed pooled data from 9 trials involving 4,957 patients with coronary artery disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (DeltaPAV) and 2-year major adverse cardiovascular event (MACE) rates when TC/HDL C levels were discordant with LDL-C, non-HDL-C, and apoB. Discordance was investigated when lipid levels were stratified by =median levels (TC/HDL-C 3.3 vs LDL-C 80, non-HDL-C 107, and apoB 76 mg/dl) or =very low percentile equivalent cutoffs (TC/HDL-C 2.5 vs LDL-C 70, non-HDL-C 89, and apoB 59 mg/dl). When stratified by median levels, TC/HDL-C was commonly observed to be discordant with LDL-C (26%), non-HDL-C (20%), and apoB (27%). In patients with LDL-C, non HDL-C, or apoB =median demonstrated less PAV regression and greater MACE (18.9%, 17.7%, 19.8%, respectively) compared with TC/HDL-C =median, those with a discordant TC/HDL-C =median (24.7%, 24.2%, 26.4%; p <0.001, 0.003, 0.03, respectively). In conclusion, the TC/HDL-C ratio reclassifies atheroma progression and MACE rates when discordant with LDL-C, non HDL-C, and apoB within subjects. Thus, using the ratio, in addition to individual lipid parameters, may identify patients who may benefit from more intensive lipid modification. PMID- 27392506 TI - Role of Coronary Angiography in the Assessment of Cardiovascular Risk in Kidney Transplant Candidates. AB - Cardiovascular disease is the leading cause of death among those with renal insufficiency, those requiring dialysis, and in recipients of kidney transplants reflecting the greatly increased cardiovascular burden that these patients carry. The best method by which to assess cardiovascular risk in such patients is not well established. In the present study, 1,225 patients seeking a kidney transplant, over a 30-month period, underwent cardiovascular evaluation. Two hundred twenty-five patients, who met selected criteria, underwent coronary angiography that revealed significant coronary artery disease (CAD) in 47%. Those found to have significant disease underwent revascularization. Among the patients found to have significant CAD, 74% had undergone a nuclear stress test before angiography and 65% of these stress tests were negative for ischemia. The positive predictive value of a nuclear stress test in this patient population was 0.43 and the negative predictive value was 0.47. During a 30-month period, 28 patients who underwent coronary angiography received an allograft. None of these patients died, experienced a myocardial infarction, or lost their allograft. The annual mortality rate of those who remained on the waiting list was well below the national average. In conclusion, our results indicate that, in renal failure patients, noninvasive testing fails to detect the majority of significant CAD, that selected criteria may identify patients with a high likelihood of CAD, and that revascularization reduces mortality both for those on the waiting list and for those who receive an allograft. PMID- 27392508 TI - Lipoprotein Metabolism and Inflammation in Patients With Psoriasis. AB - Psoriasis is a chronic inflammatory disease associated with a variety of co morbid conditions, including cardiovascular disease. Advancements in our understanding of the cellular and molecular mechanisms of psoriasis have led to a better understanding regarding its pathogenesis, which in turn has stimulated ongoing research to identify the underlying pathophysiology responsible for the increased risk of cardiovascular events associated with psoriasis. Although not yet fully elucidated, emerging evidence points to immune-mediated inflammation as a process that contributes to endothelial cell dysfunction, dyslipidemia, and atherosclerosis as key processes influencing cardiovascular disease in psoriasis. In particular, the dyslipidemia present in psoriasis may be associated with altered lipoprotein function and increased atherogenicity. Here, we review how the cytokine networks involved in lipoprotein metabolism and inflammation could impact on the cardiovascular disease risk for patients with psoriasis. PMID- 27392509 TI - Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial). AB - Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size. PMID- 27392510 TI - Long-Term Effects of Radiotherapy on Arterial Stiffness in Breast Cancer Women. AB - Radiotherapy for breast cancer may expose heart and vessels to late radiation induced complications. Although recent technical progress in radiation therapy (RT) has been associated with drastic reduction in cardiovascular (CV) mortality, the prolonged life expectancy of patients with cancer requires CV evaluation for many years. The aim of our study was to evaluate local changes in vascular and cardiac function because of previous breast RT. We enrolled 43 patients treated with RT 15 years ago for breast cancer. CV risk factors and atherosclerotic carotid damage were investigated in all women. We divided patients into 2 groups: R (n = 25) treated to right breast and L (n = 18) to left breast. All subjects were submitted to standard echocardiography and functional arteries evaluation by carotid-radial pulse-wave velocity (crPWV; Complior) and AIx (Sphygmocor; Atcor Medical). Global mean age was 69.5 +/- 8 years old. CV risk factors were equally allocated in 2 groups. No patients had history of cardiac or artery disease. R had a significantly increased crPWV (9.9 +/- 1.4 vs 8.9 +/- 1.1, p = 0.001) on right arm compared with left arm, and in L group, crPWV was similarly higher on the left arm than on right arm (9.6 +/- 1.5 vs 8.9 +/- 1.4, p = 0.011). AIx was significantly increased in the ipsilateral arm only in L (32.1 +/- 7.6 vs 28.3 +/ 6.8, p = 0.05). Central blood pressure estimation was not different in the right and left arms. No correlations were found with hormone therapy or chemotherapy. Our data show a local arterial stiffening because of radiation that can be involved in increased CV risk in breast cancer-treated patients. PMID- 27392511 TI - Clinical and Echocardiographic Factors Associated With In-Hospital Mortality in Patients With Infective Endocarditis Affecting the Native Tricuspid Valve. AB - Infective endocarditis (IE) is a highly morbid disease, for which most outcomes data come from patients with left-sided valvular lesions. Echocardiographic findings such as vegetation size and prosthetic valve involvement have been identified as important predictors of mortality in left-sided IE, but predictors of outcomes in right-sided IE are less well characterized. Therefore, the aim of this study was to identify clinical and echocardiographic findings predictive of mortality in tricuspid valve (TV) IE. We retrospectively reviewed all echocardiograms showing TV vegetations that were performed at the Massachusetts General Hospital from January 1, 2003, to December 31, 2013. We identified 105 patients who had echocardiographic evidence of TV vegetations and a definite clinical diagnosis of IE based on the modified Duke's criteria but did not have intracardiac device-associated vegetations. Of the 105 patients, 88 survived until discharge. Clinical and echocardiographic factors that positively correlated with in-hospital mortality included age (p = 0.002), immunosuppression status (p = 0.016), blood urea nitrogen level (p = 0.029), Candida causative organism (p = 0.025), left ventricular ejection fraction <40% (p = 0.027), right ventricular (RV) systolic dysfunction (p = 0.009), and estimated RV systolic pressure >40 mm Hg (p = 0.040). Of these factors, immunosuppression status, blood urea nitrogen level, and RV systolic dysfunction were independently associated with increased in-hospital mortality. In conclusion, RV systolic dysfunction may serve as an echocardiographic marker to aid clinicians in identifying high-risk patients with right-sided IE for more aggressive therapy. PMID- 27392512 TI - The SNP g.1311T>C associated with the absence of beta-casein in goat milk influences CSN2 promoter activity. AB - Quantitative individual differences in the amount of beta-casein in goat milk are determined by at least nine alleles. In particular, two alleles (CSN2(0) and CSN2(01) ) are associated with an undetectable amount of this protein in milk. The CSN2(01) allele is characterized by a single nucleotide substitution at position 373 of the seventh exon (AJ011018:g.8915C>T), responsible for the formation of a premature stop codon at the 182 position. Herein, we report the contribution of the SNP g.1311T>C, which demonstrates a linkage with the SNP AJ011018:g.8915C>T, to the promoter transcriptional activity. Particularly, we indicate that the nucleotide C at position 1311 negatively affects the promoter activity of the CSN2 gene. PMID- 27392513 TI - Long-term double-blinded unilateral pedunculopontine area stimulation in Parkinson's disease. AB - BACKGROUND: Gait-related symptoms are often refractory to current available treatment options with a significant reduction in quality of life in Parkinson's disease. OBJECTIVES: The objective of this study was to determine the long-term efficacy and safety of unilateral pedunculopontine area stimulation for refractory gait and balance impairment in Parkinson's disease. METHODS: This study used periodic randomized double-blinded assessments until 4 years postoperatively. The primary outcomes were gait-related items of the UPDRS part II and the MDS-UPDRS part III. RESULTS: At baseline, the median age and disease duration was 63 years (interquartile range: 62, 65) and 15 years (interquartile range: 11, 20). At 2 years, patient-reported freezing (UPDRS part II, off-time) was significantly better when compared with baseline (P =.028), with 62.5% of responders. At 4 years, there was no significant change in the used outcomes, but 66.7 % (n = 4 of 6) were responders for off-time patient-reported freezing and falling. CONCLUSIONS: Pedunculopontine area stimulation has an initial but not sustained benefit for gait-related symptoms. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27392514 TI - History of Orphan Drug Regulation-United States and Beyond. AB - The US Orphan Drug Act, passed in 1982, was the first orphan drug legislation in the world. It is a law based on economic incentives making it financially possible for pharmaceutical firms to develop products for small patient populations. Since passage, many additional countries have developed orphan drug programs and many pharmaceutical firms have developed around the orphan program. Today, more than 500 drugs for rare diseases have been developed in the United States. PMID- 27392515 TI - Group 1 metabotropic glutamate receptors 1 and 5 form a protein complex in mouse hippocampus and cortex. AB - The group 1 metabotropic glutamate receptors 1 and 5 (mGluR1/5) have been implicated in mechanisms of synaptic plasticity and may serve as potential therapeutic targets in autism spectrum disorders. The interactome of group 1 mGluRs has remained largely unresolved. Using a knockout-controlled interaction proteomics strategy we examined the mGluR5 protein complex in two brain regions, hippocampus and cortex, and identified mGluR1 as its major interactor in addition to the well described Homer proteins. We confirmed the presence of mGluR1/5 complex by (i) reverse immunoprecipitation using an mGluR1 antibody to pulldown mGluR5 from hippocampal tissue, (ii) coexpression in HEK293 cells followed by coimmunoprecipitation to reveal the direct interaction of mGluR1 and 5, and (iii) superresolution microscopy imaging of hippocampal primary neurons to show colocalization of the mGluR1/5 in the synapse. PMID- 27392516 TI - Covidien micro vascular plug in congenital heart diseases and vascular anomalies: A new kid on the block for premature babies and older patients. AB - OBJECTIVES: To evaluate the safety, feasibility, and efficacy of the MVPTM microvascular plug(Covidien) for closure of vascular anomalies in patients with congenital heart diseases (CHD). BACKGROUND: The MVPTM is a novel device with PTFE integrated. The device has been recently introduced in the radiological field and reported exclusively for neurological anomalies. METHODS: All CHD patients receiving the device from April 2015 until July 2015 were included in the study and followed up clinically as well as by transthoracic echocardiography. Standard safety and follow-up such as vascular complications, embolization rate, and residual shunting were assessed. RESULTS: Twelve patients with a median age of 2.6-years (0.03-12.6 years) and a mean weight of 13 kg (2.8 34.2 kg) were included. Devices were delivered from the femoral artery in 10 and from the femoral vein in 2 patients. Devices were used for closure of patent ductus arteriosus (PDA) closure (n = 5), aorto-pulmonary collaterals or Blalock Taussig shunt (n = 5), veno-venous fistula (n = 1), and coronary fistula (n = 1). One device was retrieved before release due to inappropriate size estimation (PDA spasm). The PDA was successfully closed using a PDA device (Lifetech, Medtronic). Immediate angiographic evaluation showed minimal or no shunt in 90% (10/11 patients) and 100% occlusion rate after a mean follow-up of 3.2-months. There was no device embolization, hemolysis, or any other complication following closure. CONCLUSIONS: The delivery of new MVPTM micro vascular plug system (Covidien) is safe and effective in patients with CHD for closure of a variety of vascular abnormalities. The low profile of the device and the sheathless nature of the procedure make it particularly interesting for PDA closure in premature babies. (c) 2016 Wiley Periodicals, Inc. PMID- 27392517 TI - Strong reproductive isolation and narrow genomic tracts of differentiation among three woodpecker species in secondary contact. AB - Hybrid zones allow the measurement of gene flow across the genome, producing insight into the genomic architecture of speciation. Such analysis is particularly powerful when applied to multiple pairs of hybridizing species, as patterns of genomic differentiation can then be related to age of the hybridizing species, providing a view into the build-up of differentiation over time. We examined 33 809 single nucleotide polymorphisms (SNPs) in three hybridizing woodpecker species: Red-breasted, Red-naped and Yellow-bellied sapsuckers (Sphyrapicus ruber, Sphyrapicus nuchalis and Sphyrapicus varius), two of which (ruber and nuchalis) are much more closely related than each is to the third (varius). To identify positions of SNPs on chromosomes, we developed a localization method based on comparative genomics. We found narrow clines, bimodal distributions of hybrid indices and genomic regions with decreased rates of introgression. These results suggest moderately strong reproductive isolation among species and selection against specific hybrid genotypes. We found 19 small regions of strong differentiation between species, partly shared among species pairs, but no large regions of differentiation. An association analysis revealed a single strong-effect candidate locus associated with plumage, possibly explaining mismatch among the three species in genomic relatedness and plumage similarity. Our comparative analysis of species pairs of different age and their hybrid zones showed that moderately strong reproductive isolation can occur with little genomic differentiation, but that reproductive isolation is incomplete even with much greater genomic differentiation, implying there are long periods of time when hybridization is possible if diverging populations are in geographic contact. PMID- 27392518 TI - pgm report. PMID- 27392519 TI - Coming in postgraduate medicine. PMID- 27392520 TI - From the Editor-in-Chief. PMID- 27392522 TI - What's Happening in Medicine! PMID- 27392521 TI - Problems/Solutions. PMID- 27392523 TI - Washington Report on Health. PMID- 27392524 TI - Meetings & courses. PMID- 27392527 TI - First-Principles Design of Graphene-Based Active Catalysts for Oxygen Reduction and Evolution Reactions in the Aprotic Li-O2 Battery. AB - Using first-principles density functional theory (DFT) calculations, we demonstrate that catalytic activities toward oxygen reduction and evolution reactions (ORR and OER) in a Li-O2 battery can be substantially improved with graphene-based materials. We accomplish the goal by calculating free energy diagrams for the redox reactions of oxygen to identify a rate-determining step controlling the overpotentials. We unveil that the catalytic performance is well described by the adsorption energies of the intermediates LiO2 and Li2O2 and propose that graphene-based materials can be substantially optimized through either by N doping or encapsulating Cu(111) single crystals. Furthermore, our systematic approach with DFT calculations applied to design of optimum catalysts enables screening of promising candidates for the oxygen electrochemistry leading to considerable improvement of efficiency of a range of renewable energy devices. PMID- 27392528 TI - Capillaroscopic findings and vascular biomarkers in systemic sclerosis: Association of low CD40L levels with late scleroderma pattern. AB - OBJECTIVE: To determine the relationship between vascular biomarkers reflecting the vascular injury and neoangiogenesis with capillaroscopic changes in systemic sclerosis (SSc). METHODS: Nailfold video-capillaroscopy (NVC) was performed qualitatively (early, active and late scleroderma patterns) in 72 SSc patients (66 female) fulfilling ACR/EULAR (2013) criteria. Serum samples of patients were collected and analysed by flow cytometer with multiplex kits of sCD40L, tPA, MCP 1, sE-selectin, IL-8, IL-6, VEGF, sP-selectin, TGF-beta1 and VCAM at the same time with NVC. RESULTS: Compared to healthy subjects; tPA (p=0.02), MCP-1 (p=0.001), sE-selectin (p=0.008) and TGF-beta1 (p=0.001) levels were significantly higher, however sP-selectin (p=0.011) and IL-8 (p=0.001) levels were lower in SSc patients. SSc patients were defined according to NVC patterns as 'early' (n=10), 'active' (n=37) and 'late' (n=25). According to NVC patterns of SSc patients, only sCD40L levels were significantly lower in the 'late' group (p=0.039). The other markers were similar among NVC groups. CONCLUSIONS: NVC is a useful method for investigating the vascular pathogenesis and severity of SSc. Although the levels were similar to healthy controls in patients with early/active NVC patterns, there were lower sCD40L serum levels in patients with late NVC pattern. CD40L may have a role in the early/active phase of vascular involvement. PMID- 27392529 TI - Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach. AB - Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC.HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS). Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease. PMID- 27392531 TI - [Not Available]. PMID- 27392530 TI - Origin of the vertebrate body plan via mechanically biased conservation of regular geometrical patterns in the structure of the blastula. AB - We present a plausible account of the origin of the archetypal vertebrate bauplan. We offer a theoretical reconstruction of the geometrically regular structure of the blastula resulting from the sequential subdivision of the egg, followed by mechanical deformations of the blastula in subsequent stages of gastrulation. We suggest that the formation of the vertebrate bauplan during development, as well as fixation of its variants over the course of evolution, have been constrained and guided by global mechanical biases. Arguably, the role of such biases in directing morphology-though all but neglected in previous accounts of both development and macroevolution-is critical to any substantive explanation for the origin of the archetypal vertebrate bauplan. We surmise that the blastula inherently preserves the underlying geometry of the cuboidal array of eight cells produced by the first three cleavages that ultimately define the medial-lateral, dorsal-ventral, and anterior-posterior axes of the future body plan. Through graphical depictions, we demonstrate the formation of principal structures of the vertebrate body via mechanical deformation of predictable geometrical patterns during gastrulation. The descriptive rigor of our model is supported through comparisons with previous characterizations of the embryonic and adult vertebrate bauplane. Though speculative, the model addresses the poignant absence in the literature of any plausible account of the origin of vertebrate morphology. A robust solution to the problem of morphogenesis currently an elusive goal-will only emerge from consideration of both top-down (e.g., the mechanical constraints and geometric properties considered here) and bottom-up (e.g., molecular and mechano-chemical) influences. PMID- 27392532 TI - The relationship between facial bone wall defects and dimensional alterations of the ridge following flapless tooth extraction in the anterior maxilla. AB - PURPOSE: To evaluate the relationship between defects of the facial socket wall at extraction and dimensional changes 8 weeks later in maxillary central and lateral incisor sockets. MATERIALS AND METHODS: A total of 34 consecutive patients requiring single tooth implants in the anterior maxilla (27 central and 7 lateral incisors) were evaluated. Orofacial external ridge, bone dimensions and the location of the socket bone crest were measured at extraction and again 8.5 +/- 2.91 weeks later. The status of the facial bone wall was recorded at the same time points. RESULTS: At extraction, 16 of 34 sites (47%) had intact facial bone. There were fenestration defects at 9 of 34 sites (26.5%) and dehiscence defects at 9 of 34 sites (26.5%). A significant reduction (P < 0.001) in the external orofacial ridge dimension occurred (mesial 1.4 +/- 1.30 mm or 12.1%, facial 2.5 +/- 1.46 mm or 22.2%, distal 1.1 +/- 0.83 mm or 10.5%), with greatest change at dehiscence (3.3 +/- 1.80 mm or 28.4%) and fenestration sites (2.8 +/- 1.40 mm or 24.9%). A significant reduction in orofacial bone dimension occurred (mesial 0.8 +/- 0.80 mm or 9.3%, P < 0.001; facial 1.2 +/- 1.03 mm or 18.3%, P < 0.001; distal 0.4 +/- 0.65 mm or 5.5%, P < 0.01). Vertical resorption of the bone crest was most marked at the mid-facial aspect (1.4 +/- 1.94 mm, P < 0.001). Initial fenestration defect sites demonstrated the greatest vertical dimensional change (2.9 +/- 2.67 mm; P = 0.008). Of 16 sites with initially intact facial bone, 9 sites (56.3%) developed dehiscence defects after 8 weeks. Of the 9 initial sites with fenestration defects, 5 (55.6%) turned into dehiscence defects. All 9 sites with initial dehiscence defects healed with persistence of the dehiscence. CONCLUSIONS: Eight weeks after flapless extraction of maxillary central and lateral incisors, a reduction in the orofacial dimensions of the ridge was observed due to resorption of the facial bone of the socket. Tooth type (maxillary central incisor) and thin tissue phenotype significantly influenced the outcomes. The dimensional alterations were most pronounced at sites that initially had fenestration and dehiscence defects of the facial bone. PMID- 27392534 TI - Immediate breast reconstruction following mastectomy in pregnant women with breast cancer. AB - BACKGROUND: Surgical management of breast cancer in pregnancy (BCP) requires balancing benefits of therapy with potential risks to the developing fetus. Minimal data describe outcomes after mastectomy with immediate breast reconstruction (IR) in pregnant patients. METHODS: Retrospective review was performed of patients who underwent IR after mastectomy within a BCP cohort. Parameters included intra- and post-operative complications, short-term maternal/fetal outcomes, surgery duration, and delayed reconstruction in non-IR cohort. RESULTS: Of 82 patients with BCP, 29 (35%) had mastectomy during pregnancy: 10 (34%) had IR, 19(66%) did not. All IR utilized tissue expander (TE) placement. Mean gestational age (GA) at IR was 16.2 weeks. Mean surgery duration was 198 min with IR versus 157 min without IR. Those with IR delivered at, or close to, term infants of normal birthweight. No fetal or major obstetrical complications were seen. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 (20%) patients in the IR cohort and 12 (63%) in the non-IR cohort. All patients in the IR cohort successfully transitioned to permanent implant. CONCLUSIONS: This report represents one of the largest series describing IR during BCP. IR after mastectomy increased surgery duration, but was not associated with adverse obstetrical or fetal outcomes. IR with TE may preserve reconstructive options when PMRT is indicated. J. Surg. Oncol. 2016;114:140-143. (c) 2016 Wiley Periodicals, Inc. PMID- 27392533 TI - Communicating systems in the body: how microbiota and microglia cooperate. AB - Microglia are tissue macrophages of the central nervous system (CNS). Their key tasks are immune surveillance as well as responding to infections or other pathological states such as neurological diseases or injury. In recent years it has been discovered that microglia are additionally crucial for the maintenance of brain homeostasis during development and adulthood by adjusting the neuronal network and phagocytosing neuronal debris. Microglia persist in the CNS throughout the life of the organism and self-renew without engraftment of bone marrow-derived cells. Until recently it remained unknown what controls their maturation and activation under homeostatic conditions. In this review we discuss new aspects of the interaction between host microbiota and brain function with special focus on the brain-resident innate immune cells, the microglia. PMID- 27392535 TI - [Not Available]. PMID- 27392536 TI - 2(nd) Symposium on Cardiovascular Pathophysiology in Murine Models - Paris, 26 November 2008. PMID- 27392492 TI - Poster presentations. PMID- 27392537 TI - Identification of three yeast species using the conventional and internal transcribed spacer region sequencing methods as first or second global record from human superficial infections. AB - During the mycological analysis of skin and nail samples taken from patients with onychomycosis and tineas in Assiut city, it is interesting to report that yeast fungi were the main causal agents being cultured from 45.79% of total cases. In general, 21 species of yeast were isolated. Some of these are reported for the first time from clinical specimens. From the literature available up-to-date around the world, this study reports for the first time Saccharomycopsis fibuligera as the causal agent of four clinical cases: two onychomycoses, one tinea capitis and one tinea amiantacea. Also, it is reported here the second record for Trichosporon dohaense from a case of onychomycosis of a 40-year-old woman (after its original description in 2009 by Taj-Aldeen et al. J Clin Microbiol 47: 1791). Candida galli was also reported for the first time from clinical specimen (tinea unguium) in 2014 by Galan-Sanchez et al. Mycopathol 178: 303, and this study reports the second case of onychomycosis by C. galli. These strains were identified on the basis of their phenotypic, biochemical, physiological and genotypic features. Strains and internal transcribed spacer (ITS) gene sequences of these species are deposited at Assiut University Mycological Center Culture Collection (AUMC) and National Center for Biotechnological Information (NCBI) respectively. PMID- 27392538 TI - A phase II trial of valproic acid in patients with advanced, radioiodine resistant thyroid cancers of follicular cell origin. AB - OBJECTIVE: Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer. DESIGN: An open-label Simon two-stage phase II trial. PATIENTS AND MEASUREMENTS: Valproic acid was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid-stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake. RESULTS: Thirteen patients with a median age of 66 years (50 78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hurthle cell carcinoma. None of the 10 patients who completed the 10 week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression. CONCLUSIONS: Valproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin. PMID- 27392539 TI - Living donor liver transplantation for inborn errors of metabolism - An underutilized resource in the United States. AB - Inborn metabolic diseases of the liver can be life-threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver. PMID- 27392541 TI - Overweight, obesity and the risk of gallbladder and extrahepatic bile duct cancers: A meta-analysis of observational studies. AB - OBJECTIVE: Epidemiological studies have repeatedly investigated the association between excess body weight and the risk of biliary tract cancer with inconsistent results. The objective of this study was to quantitatively assess the associations between overweight and obesity and the risk of biliary tract cancer. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to August 2015 was conducted, and the reference lists of retrieved articles for additional relevant studies were manually searched. RESULTS: Fourteen prospective cohort studies and 15 case control studies were included in this meta-analysis. These studies included 11,448,397 participants (6,733 patients with gallbladder cancer [GBC] and 5,798 patients with extrahepatic bile duct cancer [EBDC]) with follow-up durations ranging from 5 to 23 years. Among overweight adults, the pooled RR was 1.17 (95% CI, 1.07-1.28) for GBC and 1.26 (95% CI, 1.14-1.39) for EBDC, and among people with obesity, the pooled RR was 1.62 (95% CI, 1.49-1.75) for GBC and 1.48 (95% CI, 1.21-1.81) for EBDC. Visual inspection of the funnel plots and the Begg's and the Egger's tests did not show enough evidence of publication bias. CONCLUSIONS: Integrated evidence from this meta-analysis suggests that excess body weight is associated with a significantly increased risk of GBC and EBDC. PMID- 27392542 TI - Apyrase inhibitors enhance the ability of diverse fungicides to inhibit the growth of different plant-pathogenic fungi. AB - A previous study has demonstrated that the treatment of Arabidopsis plants with chemical inhibitors of apyrase enzymes increases their sensitivity to herbicides. In this study, we found that the addition of the same or related apyrase inhibitors could potentiate the ability of different fungicides to inhibit the growth of five different pathogenic fungi in plate growth assays. The growth of all five fungi was partially inhibited by three commonly used fungicides: copper octanoate, myclobutanil and propiconazole. However, when these fungicides were individually tested in combination with any one of four different apyrase inhibitors (AI.1, AI.10, AI.13 or AI.15), their potency to inhibit the growth of five fungal pathogens was increased significantly relative to their application alone. The apyrase inhibitors were most effective in potentiating the ability of copper octanoate to inhibit fungal growth, and least effective in combination with propiconazole. Among the five pathogens assayed, that most sensitive to the fungicide-potentiating effects of the inhibitors was Sclerotinia sclerotiorum. Overall, among the 60 treatment combinations tested (five pathogens, four apyrase inhibitors, three fungicides), the addition of apyrase inhibitors increased significantly the sensitivity of fungi to the fungicide treatments in 53 of the combinations. Consistent with their predicted mode of action, inhibitors AI.1, AI.10 and AI.13 each increased the level of propiconazole retained in one of the fungi, suggesting that they could partially block the ability of efflux transporters to remove propiconazole from these fungi. PMID- 27392543 TI - Mechanotransduction pulls the strings of matrix degradation at invadosome. AB - Degradation of the extracellular matrix is a critical step of tumor cell invasion. Both protease-dependent and -independent mechanisms have been described as alternate processes in cancer cell motility. Interestingly, some effectors of protease-dependent degradation are focalized at invadosomes and are directly coupled with contractile and adhesive machineries composed of multiple mechanosensitive proteins. This review presents recent findings in protease dependent mechanisms elucidating the ways the force affects extracellular matrix degradation by targeting protease expression and activity at invadosome. The aim is to highlight mechanosensing and mechanotransduction processes to direct the degradative activity at invadosomes, with the focus on membrane tension, proteases and mechanosensitive ion channels. PMID- 27392540 TI - Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer. AB - AIMS: Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. RESULTS: We demonstrate that Her2high cells and tumors have increased assembly of respiratory supercomplexes (SCs) and increased complex I-driven respiration in vitro and in vivo. They are also highly sensitive to MitoTam, a novel mitochondrial-targeted derivative of tamoxifen. Unlike tamoxifen, MitoTam efficiently suppresses experimental Her2high tumors without systemic toxicity. Mechanistically, MitoTam inhibits complex I-driven respiration and disrupts respiratory SCs in Her2high background in vitro and in vivo, leading to elevated reactive oxygen species production and cell death. Intriguingly, higher sensitivity of Her2high cells to MitoTam is dependent on the mitochondrial fraction of Her2. INNOVATION: Oncogenes such as HER2 can restructure ETC, creating a previously unrecognized therapeutic vulnerability exploitable by SC-disrupting agents such as MitoTam. CONCLUSION: We propose that the ETC is a suitable therapeutic target in Her2high disease. Antioxid. Redox Signal. 26, 84-103. PMID- 27392544 TI - [Not Available]. PMID- 27392545 TI - Good Medical Practice for Drugs. Definition, Guidelines, References, Field of Action and Applications. AB - Proper use of drugs can be defined as the use of the right product, in a correct dosage, during an adequate length of time, for a given patient and provided he has no serious side effects. It is virtually impossible, with such a number of drugs, such a number of clinical situations to prescribe adequately without using references or guidelines. References may lead to a unique choice, when the diagnosis is certain and the drug to be given is unique. With a good initial and continuous medical education, doctors can take easily this type of decision. The Summary of Products Characteristics (SPC) helps them; by sticking to this fundamental reference, prescription might be more precise and safe. In a lot of clinical situations the choice between a large numbers of therapeutic strategies necessitates use of a guideline based on scientific knowledge. Finally, a given therapeutic strategy can be as effective as and considerably less expensive than another. In such cases, payers can drive doctors to the prescription of the less expensive strategy. Some difficulties are common to all references and guidelines. PMID- 27392546 TI - [Not Available]. PMID- 27392547 TI - [Not Available]. PMID- 27392548 TI - [Not Available]. AB - ANALGESIC ACTIVITY OF DIFFERENTS NONVOLATILS EXTRACTS OF NEPETA ATLANTICA BALL AND NEPETA TUBEROSA L. SSP. RETICULATA (DESF.) MAIRE: Different extracts of Nepeta atlantica Ball and Nepeta tuberosa L. ssp. reticulata (Desf.) Maire contain mainly a secondary metabolites with iridoid lactonic and glucosidic type, also with triterpine lupan type. The aerial part of each species is crushed, then extracted in methanol by cold maceration, called global extracts. The global extracts will be extracted trough various solvents: initially by hexan then by the dichloromethan after that by the ethyl acetate and at the end by the buthanol. Each one of obtained extracts will be used for the following trials: i) Tail flick trial on the rat for the central morphine like analgesic activity; ii) Koster trial on the mouse for the peripheral analgesic activity. The evaluation of the central and peripheral analgesic activities for the pre cited extracts was realized after optimal doses determination of the global extracts activities for both species. The peripheral analgesic activity test on the mouse showed that, for 60 mg/kg intra peritoneum (IP), the hexanic, dichloromethanic, ethyl acetate and butanic extracts have a protection power against abdominal cramp respectively around 89.78%, 81.73%, 70.9% et 69.05% for Nepeta atlantica Ball, and arround 89.16%, 82.98%, 71.52% et 70.27% for Nepeta tuberosa L. ssp. reticulata. Central morphine like analgesic activity on the rat showed that, for both spices under 60 mg/kg IP, the central analgesic activity effect is significatly for two extracts only: dichloromethan and ethyl acetate. PMID- 27392549 TI - Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination? AB - OBJECTIVE: We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. METHOD: Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. RESULTS: Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. CONCLUSIONS: These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. PMID- 27392551 TI - Purification and Properties of Inulin Fructotransferase (DFA III-producing) from Bacillus sp. snu-7. AB - Inulin fructotransferase (DFA III-producing) [EC 2.4.1.93] secreted from Bacillus sp. snu-7 was purified 60.3-fold with a yield of 11.6% from a culture supernatant by ammonium sulfate precipitation, preparative isoelectrofocusing, anion exchange chromatography and preparative polyacrylamide gel electrophoresis. The purified enzyme gave a single band on polyacrylamide gel electrophoresis. The molecular mass of the enzyme was estimated to be 62 kDa on SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence was found to be Ala-Asp-Gly Gln-Asp-Gly-Ala-Pro-Leu-Asn-Gln-Val-Asn-Thr-Tyr-Asp. The optimal pH and temperature for the enzyme reaction were 6.0 and 40 degrees C, respectively. The enzyme was stable with a pH range of 4.0 to 7.0 and at up to 60 degrees C. As the production of di-D-fructose 1,2':2,3' dianhydride increased in the course of enzyme reaction, the Km of the purified enzyme was estimated to be 5.4 mM. One mM each of Cu(2+), Fe(2+) and Hg(2+) inhibited the enzyme activity strongly. Exhaustive enzymatic digestion of inulin produced 1-kestose, 1-nystose, and 1-F fructofuranosylnystose as well as di-D-fructose 1,2':2,3' dianhydride. PMID- 27392550 TI - Paper-Based Survivorship Care Plans May be Less Helpful for Cancer Patients Who Search for Disease-Related Information on the Internet: Results of the Registrationsystem Oncological Gynecology (ROGY) Care Randomized Trial. AB - BACKGROUND: The Institute of Medicine recommends Survivorship Care Plans (SCPs) for all cancer survivors. However, it is unclear whether certain patient groups may or may not benefit from SCPs. OBJECTIVE: The aim was to assess whether the effects of an automatically generated paper SCP on patients' satisfaction with information provision and care, illness perceptions, and health care utilization were moderated by disease-related Internet use. METHODS: Twelve hospitals were randomized to either SCP care or usual care in the pragmatic cluster randomized Registrationsystem Oncological GYnecology (ROGY) Care trial. Newly diagnosed endometrial cancer patients completed questionnaires after diagnosis (N=221; response: 74.7%, 221/296), 6 months (n=158), and 12 months (n=147), including patients' satisfaction with information provision and care, illness perceptions, health care utilization (how many times patients visited a medical specialist or primary care physician about their cancer in the past 6 months), and disease related Internet use (whether patients used the Internet to look for information about cancer). RESULTS: In total, 80 of 221 (36.2%) patients used the Internet to obtain disease-related information. Disease-related Internet use moderated the SCP care effect on the amount of information received about the disease (P=.03) and medical tests (P=.01), helpfulness of the information (P=.01), and how well patients understood their illness (P=.04). All stratified analyses were not statistically significant. However, it appeared that patients who did not seek disease-related information on the Internet in the SCP care arm reported receiving more information about their disease (mean 63.9, SD 20.1 vs mean 58.3, SD 23.7) and medical tests (mean 70.6, SD 23.5 vs mean 64.7, SD 24.9), finding the information more helpful (76.7, SD 22.9 vs mean 67.8, SD 27.2; scale 0-100), and understanding their illness better (mean 6.6, SD 3.0 vs mean 6.1, SD 3.2; scale 1-10) than patients in the usual care arm did. In addition, although all stratified analyses were not significant, patients who did seek disease-related information on the Internet in the SCP care arm appeared to receive less information about their disease (mean 65.7, SD 23.4 vs mean 67.1, SD 20.7) and medical tests (mean 72.4, SD 23.5 vs mean 75.3, SD 21.6), did not find the information more helpful (mean 78.6, SD 21.2 vs mean 76.0, SD 22.0), and reported less understanding of their illness (mean 6.3, SD 2.8 vs mean 7.1, SD 2.7) than patients in the usual care arm did. CONCLUSIONS: Paper SCPs appear to improve the amount of information received about the disease and medical tests, the helpfulness of the information, and understanding of the illness for patients who do not search for disease-related information on the Internet. In contrast, paper SCPs do not seem beneficial for patients who do seek disease-related information on the Internet. TRIAL REGISTRATION: ClinicalTrials.gov NCT01185626; https://clinicaltrials.gov/ct2/show/NCT01185626 (Archived by WebCite at http://www.webcitation.org/6fpaMXsDn). PMID- 27392552 TI - Under-flame Reaction of Sulfur-containing Amino Acids by a Hydrogen-Oxygen Flame. AB - Methionine was subjected to a flame-induced reaction in water or in an aqueous formic acid solution by using a hydrogen (50%)-oxygen (50%), hydrogen (87%) oxygen (13%) and hydrogen diffusion flame. Besides the already-known stepwise oxidation by a hydroxyl radical, the contribution of a hydrogen atom from the flame to the reaction was recognized when the hydrogen-rich mixtures were employed. Homoserine was obtained under all the reaction conditions employed here, and glutamic acid when employing aqueous formic acid as a solvent. A common intermediate, the 3-carboxy-3-aminopropyl radical, appeared to exist in the reaction pathway. A coupling reaction of this radical with a hydrogen atom, hydroxyl radical and hydroxycarbonyl radical afforded 2-aminobutyric acid, homoserine and glutamic acid, respectively. Lanthionine and S-methylcysteine underwent the same reactions. Increasing the hydrogen content of the fuel and adding formic acid to the solvent resulted in retarding the reaction rate. The latter modification of the reaction system also brought about greater stability of the reaction products. PMID- 27392553 TI - Novel DPPH Radical Scavengers, Bisorbicillinol and Demethyltrichodimerol, from a Fungus. AB - In our screening program for antioxidants with DPPH radical scavenging activity, we isolated four yellowish compounds from the fermentation broth of Trichoderma sp. USF-2690 strain isolated from a soil sample: two were novel compounds designated bisorbicillinol (1) and demethyltrichodimerol (2), and two were known compounds bisvertinolone (3) and trichodimerol (4). The structures of 1 and 2 were elucidated by spectroscopic evidence and chemical modification. Two compounds seemed to be the oxidized dimers of sorbicillin. In the evaluation of DPPH radical scavenging activity, bisorbicillinol gave the lowest ED50 value (31.4 MUM) among the four compounds, equal to that of BHT (27.0 MUM). PMID- 27392554 TI - Chemical Composition fo the Glue From Appressoria of Magnaporthe grisea. AB - The chemical composition of the glue substance that attaches the appressoria of Magnaporthe grisea bar artificial leaf wax was investigated. As a percentage of fresh weights, the glue was crude lipids 29.0%, proteins 12.2%, sugars 7.6%, water 26.5% and other substances 24.7%. The major fatty acid components of the crude lipids were hexadecanoic and octadecanoic acids. Unsaturated fatty acids and branched fatty acids were also detected as minor components. The protein was abundant in glycine, glutamic acid, and serine. Glucose, xylose, and mannose were the major monosaccharides. PMID- 27392555 TI - Syntheses and Potato Tuber-inducing Activity of Coronafacic Acid Analogues. AB - Coronafacic acid (1) is an acid component of coronatine, and has been isolated from several pathovars of Pseudomonas syringae. Syntheses of C6-non- and C6-alkyl substituted analogues of 1 were accomplished via intramolecular 1,6-conjugate addition as the key step. Among them, 1 and four C6-alkyl-substituted analogues exhibited potato tuber-inducing activity, but the C6-non-substituted analogue did not. It was revealed that a certain length of the C6-alkyl group was necessary to exhibit activity. PMID- 27392556 TI - Syntheses of 3-Oxa-OPC and 2-Fluoro-OPC Homologues. AB - SYNOPSIS: 3-Oxa-OPC and 2-fluoro-OPC homologues which do not undergo beta oxidation were synthesized from esters of odd-numbered OPC homologues by a short step procedure. The 3-oxa-OPC homologues were synthesized via etherification of an alcohol with tert-butyl bromoacetate under phase-transfer conditions. The 2 fluoro-OPC homologues were synthesized via the addition of the trichloromethyl anion to an aldehyde and subsequent fluorination. PMID- 27392557 TI - Crystalline Features of Chitosan-L- and D-Lactic Acid Salts. AB - The crystal structures of chitosan-L- and D-lactate salts were studied by X-ray diffraction measurements on fiber diagrams. In each lactate, chitosan took on a different crystalline polymorph depending on the preparation temperature. At low temperature, they gave a similar fiber pattern to that of the type II salt which has been found to be one of the two forms of chitosan acid salts in which the backbone chitosan molecules take on an eight-fold helix. At high temperature, however, the fiber pattern was that of the type I salt, another form of chitosan salt in which the backbone chains apparently retain the 21 symmetry of chitosan itself. The high-temperature polymorph of the L-lactate was a monoclinic (pseudoorthorhombic) unit cell whose lattice parameters were a=10.51, b=10.85, c(fiber axis)=10.34 A and gamma=90 degrees . That of the D-lactate was also a monoclinic cell having parameters a=11.20, b=11.60, c(fiber axis)=10.38 A and gamma=93.0 degrees . Their unit cell volumes coupled with their observed density values indicate that two chains of chitosan lactate were accommodated in each unit cell, that the L-lactate was an anhydrous crystal, but that the D-lactate was hydrated. The preparation temperature at which the salt changed from type II to type I was different between the D- and L-lactate, suggesting that these acids had different affinity to the chitosan molecule. When chitosan powder was suspended in a racemic lactic acid solution, the resultant solution always showed a minus sign for the rotation angle, indicating that D-lactic acid had higher affinity to chitosan than the L-isomer. PMID- 27392558 TI - Potent Antioxidative Isoflavones Isolated from Soybeans Fermented with Aspergillus saitoi. AB - Two potent antioxidative isoflavones were isolated from soybeans fermented with Aspergillus saitoi by silica gel column chromatography and preparative HPLC, using ODS column, or in addition, Toyopearl HW-40 column chromatography. The purified AS-13 and AS-9B compounds were identified as 8-hydroxydaidzein (8-OHD) and 8-hydroxygenistein (8-OHG), respectively, by MS, and (1)H-NMR, (13)C-NMR and HMBC spectra. These isoflavones, which have an o-dihydroxy structure between the 7- and 8-position, each exhibited significantly stronger antioxidative activity than daidzein and genistein in both oil and lipid/aqueous systems. Furthermore, the antioxidative activity and the content of each isoflavone analog in soybeans with different fermentation periods were investigated. It is suggested from these results that AS-13 and AS-9B were produced from daidzein and genistein, respectively, by hydroxylation at the 8-position of each isoflavone structure. In addition, it is concluded that these isoflavones were also the principal antioxidants in potent antioxidative soybeans fermented with A. saitoi. PMID- 27392559 TI - Stereoselectivity in the Michael Addition Reaction of Dialkylcuprates to the 2 Cyclohexenones with C-4 Ester Substituents. AB - Stereoselectivity in the Michael addition of (Me2C=CH)2CuMgBr and (Me2C=CH)2CuLi to 3-alkyl/H-4-[(tert-butoxycarbonyl)alkyl]-2-cyclohexenone was studied. (Me2C=CH)2CuMgBr showed stereoselectivity in all cases (3-H, Me: anti; 3-n-Bu: syn). This stereoselectivity disappeared in the reaction of (Me2C=CH)2CuLi with 4 [(tert-butoxycarbonyl)methyl]-3-butyl-2-cyclohexenone. However, the stereoselectivity was recovered by elongating the 4-alkyl chain of 2 cyclohexenone to show the same selectivity as that of (Me2C=CH)2CuMgBr. PMID- 27392560 TI - Rapid Discrimination of Mitochondrial DNA Type and Use of Results to Study Mitochondrial Inheritance in Pleurotus spp. AB - We have reported a simple and rapid method to discriminate species in the genus Pleurotus by analysis of restriction-fragment-length polymorphism of whole-cell DNA, and found that several restriction enzymes gave DNA bands useful in such discrimination, but other enzymes tested did not. In the present study, we report the reason why there were useful and useless enzymes; the effective enzymes digested rDNA into small fragments that did not interfere with the detection of DNA bands useful for discrimination. The origin of these discriminative DNA bands was found to be mitochondrial DNA when the banding profiles of whole-cell DNA, mitochondrial DNA, and nuclear DNA were compared. Consequently, our method could be used for rapid and simple identification of mitochondrial DNA type in the genus Pleurotus. The results were used to study mitochondrial inheritance, and we found that only the nucleus but not the mitochondria migrated during the mating of Pleurotus cornucopiae with P. citrinopileatus. PMID- 27392561 TI - Physiological Properties of a Neutralo-sensitive Mutant Derived from Facultative Alkaliphilic Bacillus sp. C-125. AB - A neutralo-sensitive mutant (M-12) was isolated from the facultative alkaliphilic Bacillus sp. C-125. This mutant strain was able to grow to the same extent as did the parent strain above pH 8, but did not grow below pH 7.5. The same extent of oxygen uptake was shown by the cells of the parent and mutant strains at pH 10.3. On the other hand, the oxygen uptake rate was about one-fifth of that of the parent strain at pH 7. NADH-dependent oxygen uptake by everted vesicles of the mutant was lower than that of the parent strain at pH 7-7.5, while the rate at pH 8-9 was almost identical in both strains. The activity at pH 7 of cytochrome c oxidase of right-side-out membrane vesicles of the mutant strain was lower than that of the parent strain at pH 7, while both samples had almost the same enzymatic activity at pH 8.5. These results suggest that poor respiratory activities of the mutant strain at pH 7 are the reason why this mutant strain was unable to grow at neutral pH. PMID- 27392562 TI - Okaramine G, a New Okaramine Congener from Penicillium simplicissimum ATCC 90288. AB - Okaramine G (1), a new okaramine congener, was isolated from Penicillium simplicissimum ATCC 90288. The structure of 1 was determined by a spectroscopic investigation. Okaramine G exhibited insecticidal activity against silkworms. PMID- 27392563 TI - Purification of Pomacea canaliculata alpha-Fucosidase Isoforms with Different Thermostabilities. AB - Two isoforms, F1 (pI 4.7) and F2 (pI 4.9), of alpha-fucosidase were purified from the viscera of Pomacea canaliculata. The thermostability of F1 was higher than that of F2. Both were 260-kDa proteins containing polypeptides (55 and 52 kDa) and sugar. There were small differences between F1 and F2 in the optimum conditions for the enzyme reaction and pH stability. PMID- 27392564 TI - Autoxidation Reaction Mechanism for L-Ascorbic Acid-related Compounds in Methanol without Metal Ion Catalysis. AB - The autoxidation mechanism for L-ascorbic acid (ASA)-related compounds such as D arabo-ascorbic acid (=erythorbic acid; ERA) and triose reductone (TR) in methanol without metal ion catalysis was studied. The oxidation reaction of these ASA related compounds seems to proceed via the C(2) oxygen adduct of ERA (or TR) by a similar reaction mechanism to that of ASA. PMID- 27392565 TI - Bacterial Reduction of 9-Fluorenone to 9-Hydroxyfluorene. AB - A wild type of the Gram-positive bacterium, Bacillus brevis, reduced polycyclic aromatic compounds such as 9-fluorenone to the corresponding alcohol, 9 hydroxyfluorene, at 30 degrees C in an anaerobic atmosphere in a 97% yield by extraction with an organic solvent. The products could be also continuously isolated by dialysis from a flowing reaction solution. PMID- 27392566 TI - Optical Resolution by Preferential Crystallization of (RS)-2-Amino-3-(2 carboxyethylthio)propanoic Acid. AB - Electrophilic additions of DL- and L-Cys to propenoic acid afforded (RS)- and (R) 2-amino-3-(2-carboxyethylthio)propanoic acids [(RS)- and (R)-ACE], respectively. (RS)-ACE was found to exist as a conglomerate based on its melting point, solubility, and infrared spectrum. (RS)-ACE was optically resolved by preferential crystallization to yield (R)- and (S)-ACE. The obtained (R)- and (S) ACE were efficiently recrystallized from water, taking account of the solubility of (RS)-ACE, to give them in optically pure form. PMID- 27392567 TI - Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells. AB - Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1 Hz for 4 h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for creating vascularized tissues in tissue engineering and regenerative medicine. PMID- 27392569 TI - Musculoskeletal manifestations in mucopolysaccharidosis type I (Hurler syndrome) following hematopoietic stem cell transplantation. AB - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for young Hurler patients. Despite halting of neurocognitive decline and improvement of life expectancy, the beneficial effect on the skeletal system is limited. As orthopedic complications are one of the most disabling factors following HSCT, this points to the need for new treatment strategies. The study summarizes musculoskeletal manifestations in 19 transplanted Hurler patients. METHODS: Data were obtained retrospectively. Patients' charts for physical examinations of the joint range of motion (JROM) of shoulders, elbows, hips and knees were reviewed. Radiographic evaluations of thorax, spine, pelvis and hands were performed. MRI scans of the craniocervical junction were analyzed to determine odontoid hypoplasia and the prevalence of craniocervical stenosis. RESULTS: Nineteen Hurler patients (10 females, 9 males) with an average age of 8.1 years (range 2.5-23.8) at the latest follow-up, who underwent allogenic HSCT between 1991 and 2012, were assessed after an average follow-up period of 6.4 years (range 0.7-22.5). Seventeen patients achieved long-term engraftment, two developed graft failures. The majority of patients showed a steady state or improvements in the mobility of knees (31 %/63 %), hips (47 %/40 %) and elbows (56 %/38 %). However, shoulder abduction was impaired in 3/4 of patients and showed the highest rate of progression (31 %). In patients with graft failure, progressive restrictions in JROM were noted. Assessments of the craniocervical junction by MRI showed stable or improved diameters in 67 % of patients. Correction or stabilization of odontoid hypoplasia was found in 64 %. However thoracolumbar kyphosis, scoliosis, hip dysplasia and genua valga were progressive despite HSCT. At the last follow up, 47 % of patients were partially wheelchair dependent, 10 % wheelchair bound and 25 % regularly experienced pain in the spine, hips and lower extremities due to orthopedic problems. CONCLUSION: Joint mobility, odontoid hypoplasia and craniocervical stenosis might stabilize or even improve in Hurler patients following HSCT. However, despite the beneficial effects on some musculoskeletal manifestations, skeletal complications are frequently observed and the overall burden of orthopedic disease is significant. Frequent multi-disciplinary follow-up in a specialized center are essential. Novel therapeutic approaches (e.g. anti-inflammatory drugs) are needed to improve musculoskeletal outcomes. PMID- 27392570 TI - Changes in sport and physical activity participation for adolescent females: a longitudinal study. AB - BACKGROUND: Participation in sport and physical activity is reported to decline during adolescence, particularly for females. However we do not have a clear understanding of changes in the context (i.e., modes and settings) of participation throughout adolescence. This study investigated longitudinal changes in physical activity participation and the specific modes and settings of physical activity, together with cross-sectional comparisons, for two age cohorts of female adolescents. METHODS: Survey of 729 adolescent girls (489 recruited in Year 7 and 243 in Year 11). Participation in eight different modes/settings was reported. PA was measured using 24-h recall diary and metabolic equivalent weighted energy expenditure (MET-min) in Leisure Time Moderate and Vigorous Physical Activity (LTMVPA) on the previous day was calculated. RESULTS: There were no significant changes in duration or total MET-min of LTMVPA on previous day. However, there were significant changes in the modes/settings of participation across time. Participation in school physical education rose during early adolescence before decreasing significantly, and participation in competitive sport and club sport significantly decreased over time; however there were increases in non-competitive forms of physical activity. CONCLUSIONS: Overall levels of physical activity did not significantly decrease over adolescence, which is positive for physical health. However, the transition from structured sport to non-organised physical activity may effect social and psychological health, which needs to be further examined. PMID- 27392568 TI - A new role of hindbrain boundaries as pools of neural stem/progenitor cells regulated by Sox2. AB - BACKGROUND: Compartment boundaries are an essential developmental mechanism throughout evolution, designated to act as organizing centers and to regulate and localize differently fated cells. The hindbrain serves as a fascinating example for this phenomenon as its early development is devoted to the formation of repetitive rhombomeres and their well-defined boundaries in all vertebrates. Yet, the actual role of hindbrain boundaries remains unresolved, especially in amniotes. RESULTS: Here, we report that hindbrain boundaries in the chick embryo consist of a subset of cells expressing the key neural stem cell (NSC) gene Sox2. These cells co-express other neural progenitor markers such as Transitin (the avian Nestin), GFAP, Pax6 and chondroitin sulfate proteoglycan. The majority of the Sox2(+) cells that reside within the boundary core are slow-dividing, whereas nearer to and within rhombomeres Sox2(+) cells are largely proliferating. In vivo analyses and cell tracing experiments revealed the contribution of boundary Sox2(+) cells to neurons in a ventricular-to-mantle manner within the boundaries, as well as their lateral contribution to proliferating Sox2(+) cells in rhombomeres. The generation of boundary-derived neurospheres from hindbrain cultures confirmed the typical NSC behavior of boundary cells as a multipotent and self-renewing Sox2(+) cell population. Inhibition of Sox2 in boundaries led to enhanced and aberrant neural differentiation together with inhibition in cell proliferation, whereas Sox2 mis-expression attenuated neurogenesis, confirming its significant function in hindbrain neuronal organization. CONCLUSIONS: Data obtained in this study deciphers a novel role of hindbrain boundaries as repetitive pools of neural stem/progenitor cells, which provide proliferating progenitors and differentiating neurons in a Sox2-dependent regulation. PMID- 27392571 TI - Neural substrates involved in anger induced by audio-visual film clips among patients with alcohol dependency. AB - BACKGROUND: Very little is known about the neural circuitry underlying anger processing among alcoholics. The purpose of this study was to examine the altered brain activity of alcoholic individuals during transient anger emotion. METHODS: Using functional magnetic resonance imaging (fMRI), 18 male patients diagnosed with alcohol dependence in an inpatient alcohol treatment facility and 16 social drinkers with similar demographics were scanned during the viewing of anger provoking film clips. RESULTS: While there was no significant difference in the level of experienced anger between alcohol-dependent patients and non-alcoholic controls, significantly greater activation was observed in the bilateral dorsal anterior cingulate cortex (dACC) and the right precentral gyrus among alcoholic patients compared to the normal controls. CONCLUSIONS: In summary, specific brain regions were identified that are associated with anger among patients with alcohol dependency. PMID- 27392573 TI - In Memoriam Leon Thierry (13.11.1924-07.11.2010). PMID- 27392572 TI - Diagnosing acute appendicitis using a nonoral contrast CT protocol in patients with a BMI of less than 25. AB - The objective of this study was to compare the accuracy for the diagnosis of appendicitis in patients presenting to the emergency department (ED) with acute, nontraumatic abdominal pain and a body mass index (BMI) of less than 25 before and after the implementation of a nonoral contrast computed tomography (CT) protocol with intravenous contrast. The IRB approved this HIPAA-compliant retrospective study; informed consent was waived. This study included 736 adult patients with a BMI of less than 25 presenting to our ED with acute, nontraumatic abdominal pain over two distinct 6-month time periods. An oral and intravenous contrast-enhanced protocol was utilized in the first cohort (group A), and an intravenous contrast-enhanced protocol without oral contrast was utilized in the second cohort (group B). Three abdominal fellowship-trained readers retrospectively reviewed all CT studies and electronic medical records, including surgical/pathology reports that served as reference standards. Group A consisted of 359 patients; 41 patients had surgically proven appendicitis. The sensitivity and specificity of the readers for diagnosing appendicitis in group A ranged from 95.2-100 and 98.1-99.5 %, respectively. Group B consisted of 372 patients; 39 had surgically proven appendicitis. The sensitivity and specificity of the readers in group B ranged from 92.0-100 and 98.6-100 %, respectively. There were no statistically significant differences in sensitivity or specificity for CT scans performed in groups A and B. In patients with a BMI of less than 25, an intravenous contrast-enhanced CT protocol without oral contrast demonstrates similar accuracy to an intravenous contrast-enhanced protocol with oral contrast for diagnosing acute appendicitis. PMID- 27392574 TI - The Three False Dawns of Biomedical Gerontology. PMID- 27392576 TI - Telemedicine in Neonatal Home Care: Identifying Parental Needs Through Participatory Design. AB - BACKGROUND: For the majority of preterm infants, the last weeks of hospital admission mainly concerns tube feeding and establishment of breastfeeding. Neonatal home care (NH) was developed to allow infants to remain at home for tube feeding and establishment of breastfeeding with regular home visits from neonatal nurses. For hospitals covering large regions, home visits may be challenging, time consuming, and expensive and alternative approaches must be explored. OBJECTIVE: To identify parental needs when wanting to provide neonatal home care supported by telemedicine. METHODS: The study used participatory design and qualitative methods. Data were collected from observational studies, individual interviews, and focus group interviews. Two neonatal units participated. One unit was experienced in providing neonatal home care with home visits, and the other planned to offer neonatal home care with telemedicine support. A total of 9 parents with preterm infants assigned to a neonatal home care program and 10 parents with preterm infants admitted to a neonatal unit participated in individual interviews and focus group interviews, respectively. RESULTS: Three overall themes were identified: being a family, parent self-efficacy, and nurse provided security. Parents expressed desire for the following: (1) a telemedicine device to serve as a "bell cord" to the neonatal unit, giving 24-hour access to nurses, (2) video-conferencing to provide security at home, (3) timely written email communication with the neonatal unit, and (4) an online knowledge base on preterm infant care, breastfeeding, and nutrition. CONCLUSIONS: Our findings highlight the importance of neonatal home care. NH provides parents with a feeling of being a family, supports their self-efficacy, and gives them a feeling of security when combined with nursing guidance. Parents did not request hands-on support for infant care, but instead expressed a need for communication and guidance, which could be met using telemedicine. PMID- 27392577 TI - Corrigendum to "Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer" [Exp. Cell Res. 337 (2015) 16-27]. PMID- 27392575 TI - Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction. AB - AIMS: Circulating microparticles (MPs) from metabolic syndrome patients and those generated from apoptotic T cells induce endothelial dysfunction; however, the molecular and cellular mechanism(s) underlying in the effects of MPs remain to be elucidated. RESULTS: Here, we show that both types of MPs increased expression of endoplasmic reticulum (ER) stress markers, X-box binding protein 1, p-eukaryotic translation initiation factor 2 alpha, and CHOP, and nuclear translocation of activating transcription factor 6 on human aortic endothelial cells (HAoECs). MPs decreased in vitro nitric oxide release by HAoECs, whereas in vivo MP injection into mice impaired the endothelium-dependent relaxation induced by acetylcholine. These effects were prevented when ER stress was inhibited, suggesting that ER stress is implicated in the endothelial effects induced by MPs. MPs affected mitochondrial function and evoked sequential increase of cytosolic and mitochondrial reactive oxygen species (ROS). Pharmacological inhibition of ER stress and silencing of neutral sphingomyelinase (SMase) with siRNA abrogated all MP-mediated effects. Neutralization of Fas ligand carried by MPs abolished effects induced by both MP types, whereas neutralization of low-density lipoprotein receptor on endothelial cells prevented T-lymphocyte MP-mediated effects. Innovation and Conclusion: Collectively, endothelial dysfunction triggered by MPs involves temporal cross talk between ER and mitochondria with respect to spatial regulation of ROS via the neutral SMase and interaction of MPs with Fas and/or low-density lipoprotein receptor. These results provide a novel molecular insight into the manner MPs mediate vascular dysfunction and allow identification of potential therapeutic targets to treat vascular complications associated with metabolic syndrome. Antioxid. Redox Signal. 26, 15-27. PMID- 27392578 TI - Leaching of arsenic from glazed and nonglazed potteries into foods. AB - Potteries are traditionally used for cooking and storing foods in Turkey, the Mediterranean, and Middle East regions. Leaching of inorganic arsenic into the traditional white bean dish cooked in pottery has been determined for the first time in the literature. Accuracy of this method was validated by the analysis of a certified reference material, commercially marketed standard solutions, and arsenic spiked solutions. Locally available potteries were examined for the leaching studies. Variation in the leachability of inorganic arsenic from the potteries by acetic acid versus the number of use was studied. The concentrations of arsenic leached by 4% acetic acid decreased by the usage number. The glazed potteries released arsenic at lower concentrations to leaching by acetic acid than the same group of nonglazed potteries. The concentrations of leached arsenic were relatively high in the white bean dish, where the leach of arsenic from the potteries to acetic acid was low. All of the potteries examined released inorganic arsenic to white bean dish in concentrations that exceed the daily BMDL0.5 (210MUg/day). However, because the potteries are used only about once a month, direct application of the daily dietary intake limits is not appropriate. According to the weekly BMDL0.5, the estimated contribution from arsenic was in the range of 34-79% of BMDL0.5. The results of this study showed that the potteries are the potential sources of arsenic. Pottery oiling in ovens, which is another traditional procedure before using the potteries, reduced the leaching of arsenic to foods. PMID- 27392579 TI - Microbial fuel cells for clogging assessment in constructed wetlands. AB - Clogging in HSSF CW may result in a reduction of system's life-span or treatment efficiency. Current available techniques to assess the degree of clogging in HSSF CW are time consuming and cannot be applied on a continuous basis. Main objective of this work was to assess the potential applicability of microbial fuel cells for continuous clogging assessment in HSSF CW. To this aim, two replicates of a membrane-less microbial fuel cell (MFC) were built up and operated under laboratory conditions for five weeks. The MFC anode was gravel-based to simulate the filter media of HSSF CW. MFC were weekly loaded with sludge that had been accumulating for several years in a pilot HSSF CW treating domestic wastewater. Sludge loading ranged from ca. 20kgTS.m(-3)CW.year(-1) at the beginning of the study period up to ca. 250kgTS.m(-3)CW.year(-1) at the end of the study period. Sludge loading applied resulted in sludge accumulated within the MFC equivalent to a clogging degree ranging from 0.2years (ca. 0.5kgTS.m(-3)CW) to ca. 5years (ca. 10kgTS.m(-3)CW). Results showed that the electric charge was negatively correlated to the amount of sludge accumulated (degree of clogging). Electron transference (expressed as electric charge) almost ceased when accumulated sludge within the MFC was equivalent to ca. 5years of clogging (ca. 10kgTS.m(-3)CW). This result suggests that, although longer study periods under more realistic conditions shall be further performed, HSSF CW operated as a MFC has great potential for clogging assessment. PMID- 27392580 TI - Polychlorinated biphenyls and chlorinated pesticides in king mackerel caught off the coast of Pernambuco, northeastern Brazil: Occurrence, contaminant profile, biological parameters and human intake. AB - Persistent organic pollutants such as PCBs and DDTs are ubiquitous worldwide. Their lipophilic nature facilitates accumulation in fish tissues. This study investigated 182 PCB congeners and 14 organochlorine pesticides (DDTs, HCHs, chlordanes, heptachlor and mirex) in muscle and liver of king mackerel (Scomberomorus cavalla) caught off the northeastern coast of Brazil. Concentration of PCBs, DDTs and chlordanes in muscle averaged 31.5, 4.70 and 0.15ngg(-1) dry weight (dw), respectively. Mean levels of the same contaminants in liver were 145, 18.7 and 1.11ngg(-1) dw, respectively. HCHs, heptachlor and mirex were not detected in the samples. The metabolite p,p'-DDE dominated the composition of DDTs in both muscle and liver. However, a clear shift was observed in the proportions of p,p'-DDT and p,p'-DDD when comparing both tissues, suggesting metabolism in the liver. The PCBs profile revealed a depletion in mono through tetra-CBs and an enrichment in penta- through deca-CBs. Biological parameters such as sex, maturity stage, age, body weight and total length did not influence contaminant levels in tissues. Dietary risk assessment indicated that S. cavalla from the northeastern coast of Brazil does not pose a health risk for humans. PMID- 27392581 TI - High bioconcentration of titanium dioxide nanoparticles in Daphnia magna determined by kinetic approach. AB - The environmental risk assessments of titanium dioxide nanoparticles (TiO2 NPs) have drawn wide attention and one of the required critical information is the bioconcentration potentials of these nanoparticles in aquatic organisms. In the present study, the bioconcentration of six commercially available TiO2 NPs with different sizes and surface properties were quantified in a freshwater cladoceran Daphnia magna using kinetic modeling approach. We first calculated the uptake rate constant (ku) and depuration rate constant (ke) of TiO2 NPs and then employed a first-order kinetic model to predict the bioconcentration factors (BCF) at different TiO2 NPs concentrations. Both the ku and ke of TiO2 NPs were significantly affected by the exposure concentration and the nanoparticle property. The predicted BCF values in D. magna of six TiO2 NPs ranged from 2.40*10(5)L/kg to 1.52*10(6)L/kg, and had no clear correlation with the exposure concentration. Large nominal size resulted in a lower BCF of TiO2 NPs at lower exposure concentration. Higher hydrophobicity and Al(OH)3 coating also resulted in a higher BCF. All the six TiO2 NPs in this study were therefore considered very bioaccumulative. More attention should be paid to bioconcentration in the environmental risk assessments of TiO2 NPs, and the physicochemical properties of TiO2 NPs should be taken into account. PMID- 27392583 TI - Time to Take Your Medicines, Seriously. PMID- 27392582 TI - Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. AB - Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies. Extracellular matrix (ECM) influences cellular behavior and maturation, as does the geometry of the environment-two-dimensional (2D) versus three-dimensional (3D). We therefore tested the hypothesis that native cardiac ECM and 3D cultures might enhance the maturation of iPSC-derived CMs in vitro. We demonstrate that maturation of iPSC-derived CMs was enhanced when cells were seeded into a 3D cardiac ECM scaffold, compared with 2D culture. 3D cardiac ECM promoted increased expression of calcium-handling genes, Junctin, CaV1.2, NCX1, HCN4, SERCA2a, Triadin, and CASQ2. Consistent with this, we find that iPSC derived CMs in 3D adult cardiac ECM show increased calcium signaling (amplitude) and kinetics (maximum upstroke and downstroke) compared with cells in 2D. Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum. Taken together, these studies provide novel strategies for maturing iPSC-derived CMs that may have applications in drug screening and transplantation therapies to treat heart disease. PMID- 27392585 TI - Antifungal Cyclodepsipeptides, W493 A and B, from Fusarium sp.: Isolation and Structural Determination. AB - W493 A and B, which showed strong antifungal activity, were isolated from a culture broth of Fusarium sp. The structure of W493 B was determined to be that of a cyclodepsipeptide, cyclo(3S,4R-HMTA-D-allo-Thr-L-Ala-D-Ala-L-Gln-D-Tyr-L Ile) (1) by MS and NMR data, an amino acid analysis, and synthesis of the component. HMTA represents 3-hydroxy-4-methyltetradecanoic acid. W493 A (2) had a similar structure, except that L-Ile in 1 was replaced by L-Val. The absolute configuration of each amino acid was determined by chiral HPLC, and the sequence of the components was determined by HMBC experiments. The sequence of the two alanines was determined to be a L-Ala-D-Ala by a chiral HPLC analysis of the peptide fragment containing only one Ala residue. The absolute configuration of HMTA obtained from the hydrolysis of W493 B was determined to be 3S and 4R by comparing with four isomers prepared by enantioselective synthesis via Sharpless asymmetric epoxidation. PMID- 27392584 TI - Reframing tobacco dependency management in acute care: A case study. AB - Effective tobacco dependence treatment within acute care tends to be inadequate. The purpose of the Utilizing best practices to Manage Acute care patients Tobacco Dependency (UMAT) was to implement and evaluate an evidence-based intervention to support healthcare staff to effectively manage nicotine withdrawal symptoms of acute surgical patients. Data collection for this one-year longitudinal case study included: relevant patient experiences and staff reported practice, medication usage, and chart review. Over the year each data source suggested changes in tobacco dependence treatment. Key changes in patient survey responses (N=55) included a decrease in daily smoking and cigarette cravings. Of patients who used nicotine replacement therapy, they reported an increase in symptom relief. Staff (N=45) were surveyed at baseline, mid-point and end of study. Reported rates of assessing smoking status did not change over the year, but assessment of withdrawal symptoms emerged as daily practice and questions about cessation diminished. Also delivery of nicotine replacement therapy products increased over the year. Chart reviews showed a shift in content from documenting smoking behavior to withdrawal symptoms and administration of nicotine replacements; also frequency of comments increased. In summary, the evidence based intervention influenced unit norms and reframed the culture related to tobacco dependence treatment. PMID- 27392586 TI - Antioxidative and Prooxidative Actions of Xylose-Lysine Maillard Reaction Products. AB - Maillard reaction products were prepared by heating xylose and lysine at pH 9.0 and 100 degrees C for 3 h, and then fractionated by ethyl ether and ethanol into acidic, neutral and basic low-molecular-weight, ethanol-soluble and ethanol insoluble fractions. The ethanol-soluble and -insoluble fractions were the major fractions of the xylose-lysine Maillard reaction products (XL MRPs), contributing 79.5% and 20.1%, respectively. XL MRPs revealed an inhibitory effect on linoleic acid peroxidation induced by the Fenton reaction, but did not inhibit liposome peroxidation induced by Fe(2+), where it had a prooxidative action. XL MRPs caused oxidative damage to deoxyribose and 2'-deoxyguanosine (2'-dG) induced by the Fenton reaction. The ethanol-soluble and -insoluble fractions also caused oxidative damages while the low-molecular-weight fractions displayed an antioxidative effect in inhibiting the oxidative damage to deoxyribose that was induced by the Fenton reaction. The prooxidative action of the ethanol-soluble and -insoluble fractions resembled that of the untractionated products in the 2' dG assay. In these systems with deoxyribose, 2'-dG, linoleic acid and liposomes, XL MRPs exhibited either antioxidative or prooxidative properties, which might have been due to competition between their reducing power and scavenging activity toward the hydroxyl radical. However, the low-molecular-weight fractions did not show any prooxidative activity in these oxidation systems. PMID- 27392587 TI - Cysteine Protease Inhibitors Produced by the Industrial Koji Mold, Aspergillus oryzae O-1018. AB - Aspergillus oryzae O-1018 (FERM P-15834) separated from industrial koji for brewing sake was found to produce five papain-inhibitory compounds in the culture supernatant. The five isolated inhibitors were named CPI-1 to CPI-5, and their structures were elucidated by spectroscopic analyses and chemical degradation. We determined the structures of CPI-2, CPI-3 and CPI-4 as 4-amino-1-[[N- [(2S, 3S)-3 trans-carboxyoxiran-2-carbonyl]-L-isoleucyl] amino]butane, 5-amino-1-[[N-[(2S, 3S)-3-trans-carboxyoxiran-2-carbonyl]-L-isoleucyl]amino]pentane and N (8)- [N [(2S, 3S)-3-trans-carboxyoxiran-2-carbonyl]-L-isoleu-cyl]spermidine, respectively. We also confirmed by a degradation experiment that CPI-1 consisted of L-trans-epoxysuccinic acid, L-tyrosine and spermidine, and that CPI-5 was composed of L-trans-epoxysuccinic acid, L-phenylalanine and spermidine. Although CPI-4 was identified as kojistatin A,(1)) the other CPIs seemed to be novel compounds. All CPIs were cysteine protease-specific inhibitors with appreciable selectivity toward cathepsin B and L. The inhibition potency of CPIs against cysteine proteases was as high as or higher than that of E-64. In particular, CPI 2, -3 and -4 were ten times more effective than E-64 toward cathepsin B and L, and CPI-1 and -5 were about 100 times more inhibitory than E-64 toward cathepsin L. PMID- 27392588 TI - Synthesis of a Lectin in Both Mycelia and Fruit Bodies of the Ascomycete Mushroom Aleuria aurantia. AB - In several organisms that form fruit bodies, the synthesis of lectins is developmentally regulated. Aleuria aurantia is an ascomycete that forms a fruit body known as orange peel mushroom. To find whether the mycelia of this organism synthesize a lectin, mycelial isolates were obtained from a wild fruit body by spore germination and regeneration from a fragment of the fruit body. The isolates were identified as A. aurantia by analysis of their DNA. The mycelial isolates synthesized a lectin with the same properties as those of fruit-body lectin in terms of subunit molecular mass, immunochemical reactivity, binding specificity for L-fucose, and N-terminal amino acid sequence. Vegetatively growing mycelia synthesized as much lectin as the fruit body, so such synthesis was not developmentally regulated, unlike some other organisms that form fruit bodies. PMID- 27392589 TI - Improvement of the Off-flavor of Soy Protein Isolate by Removing Oil-body Associated Proteins and Polar Lipids. AB - The precipitate formed by ultracentrifuging a defatted soybean extract at 200,000*g for 50 min at pH 7.5 was composed of particles of 100-200 nm in diameter and enriched with 34-kDa, 24-kDa and 18-kDa proteins. An SDS-PAGE analysis showed these proteins to migrate to a position identical to that of oil body-associated proteins (OBAPs; Herman, Planta, 172, 336-345, 1987).(1)) They were recovered in the precipitate of soy protein with 30-40% saturated ammonium sulfate in the presence of 10 mM 2-ME. The lipid composition of the precipitate by a TLC analysis showed that most of the polar lipids in the soybean extract had been condensed in the fraction, suggesting the association between OBAP and the polar lipids. Removal of OBAP and the polar lipids from the soybean extract by conventional centrifugation (10,000*g for 10 min) in the presence of 30 mM Na2SO4 and 30 mM CaCl2 at pH 2.8 was achieved with concomitant improvement of the volatile off-flavor. A soy protein isolate (SPI) prepared from such a soybean extract contained far fewer volatile off-flavor compounds than normal SPI did. PMID- 27392590 TI - Reduction of Stale Aldehyde of Beer with Membrane Fraction of Acetic Acid Bacteria. AB - The oxidation of trans-2-nonenal, the main compound causing staleness in beer, with a membrane fraction of acetic acid bacteria was investigated. For use of the fraction, it was necessary to inactivate membrane-bound alcohol dehydrogenase (ADH) first to avoid oxidation of alcohol, while maintaining membrane-bound aldehyde dehydrogenase (ALDH) activity. ADH was completely inactivated by treatment of the membrane fraction at 60 degrees C for 15 min, without any loss of ALDH activity. ALDH activity was not affected by heat treatment even in the presence of 10% alcohol. Results of HPLC showed that a fraction incubated at 60 degrees C for 15 min oxidized 50 ppb trans-2-nonenal added to a commercial beer sample without affecting the alcohol content. Our sensory panel found that the stale odor of trans-2-nonenal disappeared when the membrane fraction was so treated, with the resulting odor better than that of beer with trans-2-nonenal added but not treated with the fraction. PMID- 27392591 TI - Benzaldehyde O-Alkyloximes as New Plant Growth Regulators. AB - Fourty-two kinds of benzaldehyde O-alkyloximes derived from benzaldehydes were prepared and their biological activities were investigated. Introduction of a fluorine or bromine atom to the benzene ring of the oximes enhanced their phytotoxic activity. The O-alkyloximes with a fluorine atom at the 3 or 4 position of the benzene ring were more active than the other oximes in the GA3 induced alpha-amylase induction inhibition test. In the transpiration test, 4 bromobenzaldehyde O-carboxylmethyloxime was the most active. The O-alkyloximes exhibited weak abscisic acid-like activity by inhibiting not only the germination, root growth and transpiration of higher plants but also GA3-induced alpha-amylase induction in embryoless barley seeds. PMID- 27392592 TI - 4-Hydroxy-3-nitrophenylacetic and Sinapic Acids as Antibacterial Compounds from Mustard Seeds. AB - A methanol extract from yellow mustard seeds had antibacterial activity against Escherichia coli, Salmonella enteritidis, and Staphylococcus aureus. Two compounds with such activity were isolated from the extract. By instrumental analysis, the compounds were identified as 4-hydroxy-3-nitrophenylacetic and sinapic acids. Examination of the structure-activity relationship showed that the hydroxyl and nitro groups of the first compound were involved in the activity against all three species. The two methoxyl groups and the hydroxyl group in sinapic acid were effective against E. coli and all of the substituents of the benzene ring were effective against S. enteritidis. The presence of the propenoic group of the second compound was effective against S. aureus. PMID- 27392593 TI - Manauealide C and Anhydrodebromoaplysiatoxin, Toxic Constituents of the Hawaiian Red Alga, Gracilaria coronopifolia. AB - Manauealide C (1) and anhydrodebromoaplysiatoxin (4), toxic constituents of the Hawaiian red alga, Gracilaria coronopifolia which has been concerned with food poisoning cases, were studied. The absolute structure of manauealide C was determined as 1 by chemical conversion and spectroscopic methods. The first complete assignment of (13)C chemical shifts for anhydrodebromoaplysiatoxin (4) was established. The biological activity of 4 was also investigated. PMID- 27392594 TI - Nisin Z Production by Lactococcus lactis IO-1 Using Xylose as a Carbon Source. AB - Lactococcus lactis IO-1 was able to use xylose as a carbon source for nisin Z production; the yield based on sugar consumption was about 20% superior to that made with glucose under the same fermentation conditions. The optimal conditions for nisin Z production were with 4% xylose at pH 6.0 and 37 degrees C. Addition of 0.1 M CaCl2 increased nisin Z production specifically, but not cell growth, acid production, or xylose consumption, and resulted in the maximum nisin Z activity of about 1.5 times that without CaCl2. PMID- 27392596 TI - The hypnotic bromovalerylurea ameliorates 6-hydroxydopamine-induced dopaminergic neuron loss while suppressing expression of interferon regulatory factors by microglia. AB - The low molecular weight organic compound bromovalerylurea (BU) has long been used as a hypnotic/sedative. In the present study, we found that BU suppressed mRNA expression of proinflammatory factors and nitric oxide release in lipopolysaccharide (LPS)-treated rat primary microglial cell cultures. BU prevented neuronal degeneration in LPS-treated neuron-microglia cocultures. The anti-inflammatory effects of BU were as strong as those of a synthetic glucocorticoid, dexamethasone. A rat hemi-Parkinsonian model was prepared by injecting 6-hydroxydopamine into the right striatum. BU was orally administered to these rats for 7 days, which ameliorated the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and alleviated motor deficits. BU suppressed the expression of mRNAs for interferon regulatory factors (IRFs) 1, 7 and 8 in the right (lesioned) ventral midbrain as well as those for proinflammatory mediators. BU increased mRNA expression of various neuroprotective factors, including platelet-derived growth factor and hepatocyte growth factor, but it did not increase expression of alternative activation (M2) markers. In microglial culture, BU suppressed the LPS-induced increase in expression of IRFs 1 and 8, and it reduced LPS-induced phosphorylation of JAK1 and STATs 1 and 3. Knockdown of IRFs 1 and 8 suppressed LPS-induced NO release by microglial cells. These results suggest that suppression of microglial IRF expression by BU prevents neuronal cell death in the injured brain region, where microglial activation occurs. Because many Parkinsonian patients suffer from sleep disorders, BU administration before sleep may effectively ameliorate neurological symptoms and alleviate sleep dysfunction. PMID- 27392595 TI - Hydroalcoholic extract and pure compounds from Senecio nutans Sch. Bip (Compositae) induce vasodilation in rat aorta through endothelium-dependent and independent mechanisms. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America, and is used in herbal medicine in Andean communities for treating acute mountain sickness. Currently, the direct effects of hydroalcoholic extract of S. nutans (HAE S. nutans) or its isolated compounds on the vascular system are not well described. The aim of this study was to determine the effects and mechanism of action of S. nutans on vascular function in healthy rats. MATERIAL AND METHODS: Seven compounds were isolated from the HAE S. nutans, and their structures were characterized using spectroscopic techniques as 1D and 2D NMR, and mass spectrometry. Vascular reactivity experiments were carried out in rat aorta. S. nutans-dependent vasodilation and phenylephrine dependent contraction were measured in endothelium-intact and endothelium-denuded aortic rings of male rats. RESULTS: Seven pure compounds were isolate from HAE S. nutans, but two pure compounds showed significant vasodilation in rat aorta: 4 hydroxy-3-(3-methyl-2-butenyl)acetophenone (compound E) and 5-acetyl-6-hydroxy-2 isopropenyl-2,3-dihydrobenzofurane (compound G). Although HAE S. nutans induced vasodilation in absence of endothelium, the vasodilation in intact aorta, via NO, was higher. HAE S. nutans reduced calcium-dependent contraction in endothelium intact, but not in endothelium-denuded aortic rings. CONCLUSION: HAE S. nutans and its isolated compounds caused vasodilation in rat aorta in absence of endothelium, suggesting its vasodilator properties is endothelium-dependent (NO) and or independent, and may involve a modulation of the calcium channels. This result is of clinical interest as potential therapy control of blood pressure. PMID- 27392598 TI - [Not Available]. PMID- 27392597 TI - Failure of the Current Advance Care Planning Paradigm: Advocating for a Communications-Based Approach. AB - The purpose of advance care planning (ACP) is to allow an individual to maintain autonomy in end-of-life (EOL) medical decision-making even when incapacitated by disease or terminal illness. The intersection of EOL medical technology, ethics of EOL care, and state and federal law has driven the development of the legal framework for advance directives (ADs). However, from an ethical perspective the current legal framework is inadequate to make ADs an effective EOL planning tool. One response to this flawed AD process has been the development of Physician Orders for Life Sustaining Treatment (POLST). POLST has been described as a paradigm shift to address the inadequacies of ADs. However, POLST has failed to bridge the gap between patients and their autonomous, preferred EOL care decisions. Analysis of ADs and POLST reveals that future policy should focus on a communications-based approach to ACP that emphasizes ongoing interactions between healthcare providers and patients to optimize EOL medical care to the individual patient. PMID- 27392599 TI - [Mecanisme de thrombocytopenie peripherique induite par l'amoxicilline : a propos d'un cas]. PMID- 27392600 TI - Cryo-EM structure of a tetrameric cyanobacterial photosystem I complex reveals novel subunit interactions. AB - Photosystem I (PSI) of the thermophilic cyanobacterium Chroococcidiopsis sp. TS 821 (TS-821) forms tetramers Li et al. (2014). Two-dimensional maps obtained by single particle electron microscopy (EM) clearly show that the tetramer lacks four-fold symmetry and is actually composed of a dimer of dimers with C2 symmetry. The resolution of these negative stain 2D maps did not permit the placement of most of the small PSI subunits, except for PsaL. Therefore cryo-EM was used for 3D reconstruction of the PSI tetramer complex. A 3D model at ~11.5A resolution was obtained and a 2D map within the membrane plane of ~6.1A. This data was used to build a model that was compared with the high-resolution structure of the PSI of Thermosynechococcus elongatus (T. elongatus) at 2.5A. This comparison reveals key differences in which subunits are involved in the two different interfaces, interface type 1 within a dimer and interface type 2 between dimers. The type 1 interface in TS-821 is similar to the monomer interface in the trimeric PSI from T. elongatus, with interactions between subunits PsaA, -B, -I, -L and M. In type 2 the interaction is only between PsaA, B and -L. Unlike the trimeric PSI, the central cavity of the complex is not filled with the PsaL-derived helical bundle, but instead seems filled with lipids. The physiological or evolutionary advantage of the tetramer is unknown. However, the presence of both dimers and tetramers in the thylakoid membrane suggest a dynamic equilibrium that shifts towards the tetramers in high light. PMID- 27392601 TI - Carotid artery dissection and motor vehicle trauma: patient demographics, associated injuries and impact of treatment on cost and length of stay. AB - BACKGROUND: Blunt carotid arterial injury (BCI) is a rare injury associated with motor vehicle collision (MVC). There are few population based analyses evaluating carotid injury associated with blunt trauma and their associated injuries as well as outcomes. METHODS: The Nationwide Inpatient Sample (NIS) 2003-2010 data was queried to identify patients after MVC who had documented BCI during their hospitalizations utilizing ICD-9-CM codes. Demographics, associated injuries, interventions performed, length of stay, and cost were evaluated. RESULTS: 1,686,867 patients were estimated having sustained MVC; 1,168 BCI were estimated. No patients with BCI had open repair, 4.24 % had a carotid artery stent (CAS), and 95.76 % of patients had no operative intervention. Age groups associated with BCI were: 18-24 (27.8 %), 47-60 (22.3 %), 35-46 (20.6 %), 25-34 (19.1 %), >61 (10.2 %). Associated injuries included long bone fractures (28.5 %), stroke and intracranial hemorrhage (28.5 %), cranial injuries (25.6 %), thoracic injuries (23.6 %), cervical fractures (21.8 %), facial fractures (19.9 %), skull fractures (18.8 %), pelvic fractures (18.5 %), hepatic (13.3 %) and splenic (9.2 %) injuries. Complications included respiratory (44.2 %), bleeding (16.1 %), urinary tract infections (8.9 %), and sepsis (4.9 %). Overall mortality was 14.1 % without differences with regard to intervention (18.5 % vs. 13.9 %; P = 0.36). Stroke and intracranial hemorrhage was associated with a 2.7 times greater risk of mortality. Mean length of stay for patients with BCI undergoing stenting compared to no intervention were similar (13.1 days vs. 15.9 days) but had a greater mean cost ($83,030 vs. $63,200, p = 0.3). CONCLUSION: BCI is a rare injury associated with MVC, most frequently reported in younger patients. Frequently associated injuries were long bone fractures, stroke and intracranial hemorrhage, thoracic injuries, and pelvic fractures which are likely associated with the force/mechanism of injury. The majority of patients were treated without intervention, but when CAS was utilized, it did not impact mortality and trended toward increased costs. PMID- 27392602 TI - Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats. AB - BACKGROUND AND AIM: Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin induced Crohn's disease in rats. EXPERIMENTAL APPROACH: Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-alpha, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. RESULTS: Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-alpha, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. CONCLUSION: The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. PMID- 27392604 TI - Polymeric nanocapsules: a potential new therapy for corneal wound healing. AB - Corneal injuries are one of the most frequently observed ocular diseases, leading to permanent damage and impaired vision if they are not treated properly. In this sense, adequate wound healing after injury is critical for keeping the integrity and structure of the cornea. The goal of this work was to assess the potential of polymeric nanocapsules, either unloaded or loaded with cyclosporine A or vitamin A, alone or in combination with mitomycin C, for the treatment of corneal injuries induced by photorefractive keratectomy surgery. The biopolymers selected for the formation of the nanocapsules were polyarginine and protamine, which are known for their penetration enhancement effect. The results showed that, following topical instillation to a mouse model of corneal injury, all the nanocapsule formulations, either unloaded or loaded with cyclosporine A or vitamin A, were able to stimulate corneal wound healing. In addition, the healing rate observed for the combination of unloaded protamine nanocapsules with mitomycin C was comparable to the one observed for the positive control Cacicol(r), a biopolymer known as a corneal wound healing enhancer. Regarding the corneal opacity, the initial grade of corneal haze (>3) induced by the photorefractive keratectomy was more rapidly reduced in the case of the positive control, Cacicol(r), than in corneas treated with the nanocapsules. In conclusion, this work shows that drug-free arginine-rich (polyarginine, protamine) nanocapsules exhibit a positive behavior with regard to their potential use for corneal wound healing. PMID- 27392603 TI - Origins, structures, and functions of circulating DNA in oncology. AB - While various clinical applications especially in oncology are now in progress such as diagnosis, prognosis, therapy monitoring, or patient follow-up, the determination of structural characteristics of cell-free circulating DNA (cirDNA) are still being researched. Nevertheless, some specific structures have been identified and cirDNA has been shown to be composed of many "kinds." This structural description goes hand-in-hand with the mechanisms of its origins such as apoptosis, necrosis, active release, phagocytosis, and exocytose. There are multiple structural forms of cirDNA depending upon the mechanism of release: particulate structures (exosomes, microparticles, apoptotic bodies) or macromolecular structures (nucleosomes, virtosomes/proteolipidonucleic acid complexes, DNA traps, links with serum proteins or to the cell-free membrane parts). In addition, cirDNA concerns both nuclear and/or mitochondrial DNA with both species exhibiting different structural characteristics that potentially reveal different forms of biological stability or diagnostic significance. This review focuses on the origins, structures and functional aspects that are paradoxically less well described in the literature while numerous reviews are directed to the clinical application of cirDNA. Differentiation of the various structures and better knowledge of the fate of cirDNA would considerably expand the diagnostic power of cirDNA analysis especially with regard to the patient follow-up enlarging the scope of personalized medicine. A better understanding of the subsequent fate of cirDNA would also help in deciphering its functional aspects such as their capacity for either genometastasis or their pro inflammatory and immunological effects. PMID- 27392605 TI - Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action. AB - Efforts to reduce the global burden of bacterial disease and contend with escalating bacterial resistance are spurring innovation in antibacterial drug and biocide development and related technologies such as photodynamic therapy and photochemical disinfection. Elucidation of the mechanism of action of these new agents and processes can greatly facilitate their development, but it is a complex endeavour. One strategy that has been popular for many years, and which is garnering increasing interest due to recent technological advances in microscopy and a deeper understanding of the molecular events involved, is the examination of treated bacteria for changes to their morphology and ultrastructure. In this review, we take a critical look at this approach. Variables affecting antibacterial-induced alterations are discussed first. These include characteristics of the test organism (e.g. cell wall structure) and incubation conditions (e.g. growth medium osmolarity). The main body of the review then describes the different alterations that can occur. Micrographs depicting these alterations are presented, together with information on agents that induce the change, and the sequence of molecular events that lead to the change. We close by highlighting those morphological and ultrastructural changes which are consistently induced by agents sharing the same mechanism (e.g. spheroplast formation by peptidoglycan synthesis inhibitors) and explaining how changes that are induced by multiple antibacterial classes (e.g. filamentation by DNA synthesis inhibitors, FtsZ disruptors, and other types of agent) can still yield useful mechanistic information. Lastly, recommendations are made regarding future study design and execution. PMID- 27392608 TI - Structure, Diversity, and Evolution of a New Family of Soluble Carotenoid-Binding Proteins in Cyanobacteria. AB - Using a phylogenomic approach, we have identified and subclassified a new family of carotenoid-binding proteins. These proteins have sequence homology to the N terminal domain (NTD) of the Orange Carotenoid Protein (OCP), and are referred to as Helical Carotenoid Proteins (HCPs). These proteins comprise at least nine distinct clades and are found in diverse organisms, frequently as multiple paralogs representing the distinct clades. These seem to be out-paralogs maintained from ancient duplications associated with subfunctionalization. All of the HCPs share conservation of the residues for carotenoid binding, and we confirm that carotenoid binding is a fundamental property of HCPs. We solved two crystal structures of the Nostoc sp. PCC 7120 HCP1 protein, each binding a different carotenoid, suggesting that the proteins flexibly bind a range of carotenoids. Based on a comprehensive phylogenetic analysis, we propose that one of the HCP subtypes is likely the evolutionary ancestor of the NTD of the OCP, which arose following a domain fusion event. However, we predict that the majority of HCPs have functions distinct from the NTD of the OCP. Our results demonstrate that the HCPs are a new family of functionally diverse carotenoid binding proteins found among ecophysiologically diverse cyanobacteria. PMID- 27392609 TI - Development of in vivo imaging. PMID- 27392606 TI - Mechanisms of viral mutation. AB - The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host dependent processes, and that viral mutation rates can evolve in response to specific selective pressures. PMID- 27392610 TI - Actinobacteria possessing antimicrobial and antioxidant activities isolated from the pollen of scots pine (Pinus sylvestris) grown on the Baikal shore. AB - Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Scots pine trees (Pinus sylvestris) growing on the shore of the ancient Lake Baikal in Siberia. In addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens. PMID- 27392611 TI - Impact of the intermediary layer on sealant retention: a randomized 24-month clinical trial. AB - OBJECTIVES: The aims of this study were to assess long-term impact of tooth eruption stages (ES) on sealant retention on occlusal surfaces previously coated with intermediary bonding layer and to determine caries prevention. MATERIALS AND METHODS: Sixty-five school children were selected (aged 6-10 years), with four non-carious permanent first molar in different ES (OP (operculum present), ME (marginal edge), CE (completely erupted)). Split-mouth and single-blind study design was used. The teeth (260) were randomly selected according to treatment (sealant/technique): F (Fluroshield), H (Helioseal Clear Chroma), SF (Single Bond + F), EH (Excite + H). Sealant retention, marginal integrity, discoloration, and caries prevention were assessed after 6, 12, 18, and 24 months by calibrated examiner (Spearman = 0.91) using visual inspection. Data were submitted to the Cox proportional hazard model (survival analysis) and Likelihood ratio chi 2 test (correlation), p <= 0.05. RESULTS: At baseline, ES was 20 % in OP, 54 % in ME, and 26 % in CE. There was no significant difference on sealant retention between the treatments (p = 0.2774). However, significant differences were found regarding the ES on sealant retention (p = 0.0041). The CE stage showed the highest retention survival rate during the 24 months. The overall sealant prevention average was found to be about 99.4 % and showed no difference between the groups. CONCLUSIONS: Eruption stages affect sealant retention irregardless of the intermediate layer and type of sealant. However, there was caries prevention on tooth occlusal surfaces after 24 months, regardless of treatment. CLINICAL RELEVANCE: Sealing is recommended to prevent occlusal caries of newly erupted teeth in high-caries-risk patients. However, its application is critical on moisture limited control surfaces independently of sealer material and technique. PMID- 27392612 TI - Preventive and invasive treatment in special needs patients: a German retrospective study. AB - OBJECTIVES: Data on dental treatment of children with special healthcare needs (CSHCN) are sparse. Hence, this study provides information about the changes in the dental condition in a cohort of CSHCN treated in a university dental department in Germany. MATERIAL AND METHODS: Patient records of CSHCN treated from January 2004 to December 2012 were screened retrospectively for medical diagnoses (ICD-10) and the type of treatment performed with outpatient dental care (ODC) or general anesthesia (GA). Follow-up data of patients adhering to the recommended recall were recorded, including time and further treatments. RESULTS: A total of 795 CSHCN with a mean age of 6.8 years were included. In 41.6 % (331/795) of cases, treatment was performed under ODC, and 58.4 % (464/795) received GA. Caries experience in CSHCN treated under GA was significantly higher (7.9 d3/4mft/0.9 D3/4MFT) than in ODC (2.5 d3/4mft /0.9 D3/4MFT). Over time, patient flow shifted from invasive (IC) to preventive-based care (PC). CONCLUSION: Caries-related treatments were most frequent under GA and ODC, though initial caries experience was higher in GA patients. The choice of GA or ODC was statistically independent from the medical condition. CLINICAL SIGNIFICANCE: This study provides characteristics of a large population of CSHCN treated with and without GA for dental care. PMID- 27392607 TI - Epigenetic regulation of epithelial-mesenchymal transition. AB - Epithelial-mesenchymal transition (EMT) is an essential process for morphogenesis and organ development which reversibly enables polarized epithelial cells to lose their epithelial characteristics and to acquire mesenchymal properties. It is now evident that the aberrant activation of EMT is also a critical mechanism to endow epithelial cancer cells with migratory and invasive capabilities associated with metastatic competence. This dedifferentiation program is mediated by a small cohort of pleiotropic transcription factors which orchestrate a complex array of epigenetic mechanisms for the wide-spread changes in gene expression. Here, we review major epigenetic mechanisms with an emphasis on histone modifications and discuss their implications in EMT and tumor progression. We also highlight mechanisms underlying transcription regulation concerted by various chromatin modifying proteins and EMT-inducing transcription factors at different molecular layers. Owing to the reversible nature of epigenetic modifications, a thorough understanding of their functions in EMT will not only provide new insights into our knowledge of cancer progression and metastasis, but also facilitate the development of diagnostic and therapeutic strategies for human malignancy. PMID- 27392614 TI - [Not Available]. AB - The use of amikacin is difficult because of its toxicity and its pharmacokinetic variability. This variability is almost ignored in adult standard dosage regimens since only the weight is used in the dose calculation. Our objective is to test if the pharmacokinetic of amikacin can be regarded as homogenous, and if the method for calculating the dose according to patients' weight is appropriate. From a cohort of 580 patients, five groups of patients were created by statistical data partitioning. A population pharmacokinetic analysis was performed in each group. The adult population is not homogeneous in term of pharmacokinetics. The doses required to achieve a maximum concentration of 60mg/L are strongly different (585 to 1507mg) between groups. The exclusive use of the weight to calculate the dose of amikacine appears inappropriate for 80% of the patients, showing the limits of the formulae for calculating doses of aminoglycosides. PMID- 27392613 TI - An ex vivo comparison of working length determination by three electronic root canal length measurement devices integrated into endodontic rotary motors. AB - AIM: The objective of this study was to compare the accuracy of working length (WL) determination by X-Smart Dual, ENDOAce, and Gold Reciproc motor, in manual mode and mechanical preparation set to auto apical reverse (AAR) mode. MATERIALS AND METHODS: Forty-five anterior teeth were included in the study. The canal length was determined by introducing #10 file into the canal until it emerged at the apical foramen. The incisal edges were adjusted to obtain 18 mm standard length. The teeth were embedded in Plexiglas tubes, filled with alginate, and measured in manual and AAR modes. RESULTS: Within and between the groups, there was no significant difference in WL measurements, both in manual and AAR modes. In the X-Smart Dual group, all manual measurements were within root canal limits, while 13 % of AAR mode measurements were recorded when the file tip passed the apical foramen. In the ENDOAce group, 13 and 7 % of the measurements, in manual and AAR modes respectively, were recorded when the file tip passed the foramen. In the Gold Reciproc motor group, 27 and 33 % of the measurements, in manual and AAR modes respectively, were recorded when the file tip passed the foramen. CONCLUSION: With the limitation of this ex vivo study, the tested devices presented no significant differences in length measurements and were within the clinical accepted margin of error. CLINICAL RELEVANCE: Mechanical preparation must be confined to the root canal system. The adverse results of overinstrumentation emphasize the need to reconsider the +/-0.50 mm margin of error that is clinically acceptable for WL measurements. PMID- 27392616 TI - Introducing Donor Milk in a Neonatal Intensive Care Unit: A Developing Country's Perspective: Correspondence. PMID- 27392615 TI - Malignant lipogenesis defined by 11C-acetate PET/CT predicts prostate cancer specific survival in patients with biochemical relapse after prostatectomy. AB - PURPOSE: Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. 11C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse 11C acetate PET/CT image metrics in relation to survival. METHODS: All patients undergoing 11C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding 11C-acetate uptake intensity (SUVmax) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUVmax * TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis. RESULTS: A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 +/- 4.35 ng/mL. The median follow-up of the study population was 79 +/- 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUVmax (r = -0.55, p = 0.01) and nonlinearly with TLA (r = -0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045). CONCLUSION: Malignant 11C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death. 11C-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit. PMID- 27392617 TI - Editorial: Pediatric Orthopedics at the Doorstep of the Pediatrician. PMID- 27392618 TI - Joubert Syndrome Mimicking Hypotonic Cerebral Palsy. PMID- 27392619 TI - Hypophosphatemia in Critically Ill Children: Risk Factors, Outcome and Mechanism. AB - OBJECTIVES: To determine the prevalence of hypophosphatemia in critically ill children and its association with clinical outcomes; to determine risk factors and mechanism of hypophosphatemia. METHODS: Levels of serum phosphate, phosphate intake, renal phosphate handling indices and blood gases were measured on days 1, 3, 7 and 10 of pediatric intensive care unit (PICU) stay. Hypophosphatemia was defined as any serum phosphorus <3.8 mg/dl for children younger than 2 y and <3.5 mg/dl for children 2 y or older. Renal phosphate loss was assessed using the ratio of tubular maximum reabsorption of phosphate (TmP) to glomerular filtration rate (GFR) [TmP/GFR]. RESULTS: Prevalence of hypophosphatemia was 71.6 % (95 % CI: 64.6-78.6). On adjusted analysis, hypophosphatemia was associated with prolonged PICU length of stay (PICU LOS > 6 d) (adjusted OR: 3.0 [95 % CI: 1.4 6.7; p = 0.005]) but not associated with increased mortality. Renal phosphate threshold was significantly lower on all the days in hypophosphatemic group compared to that of non-hypophosphatemic group. No statistically significant difference in the amount of phosphate intake was seen in both the groups. CONCLUSIONS: Hypophosphatemia is highly prevalent in critically ill children and is associated with prolonged PICU LOS. Increased phosphate loss in urine is one of the mechanism responsible for hypophosphatemia in critically ill children. PMID- 27392620 TI - Comparing estimates of EMEP MSC-W and UFORE models in air pollutant reduction by urban trees. AB - There is a growing interest to identify and quantify the benefits provided by the presence of trees in urban environment in order to improve the environmental quality in cities. However, the evaluation and estimate of plant efficiency in removing atmospheric pollutants is rather complicated, because of the high number of factors involved and the difficulty of estimating the effect of the interactions between the different components. In this study, the EMEP MSC-W model was implemented to scale-down to tree-level and allows its application to an industrial-urban green area in Northern Italy. Moreover, the annual outputs were compared with the outputs of UFORE (nowadays i-Tree), a leading model for urban forest applications. Although, EMEP/MSC-W model and UFORE are semi empirical models designed for different applications, the comparison, based on O3, NO2 and PM10 removal, showed a good agreement in the estimates and highlights how the down-scaling methodology presented in this study may have significant opportunities for further developments. PMID- 27392621 TI - The effects of PM10 on electrocardiogram parameters, blood pressure and oxidative stress in healthy rats: the protective effects of vanillic acid. AB - Particulate matter (PM) inhalation is an established trigger of cardiovascular events such as cardiac arrhythmias that occur within hours to days after exposure. Higher daily PM levels are related to acute increases in systemic arterial blood pressure (BP). The aim of the present study was to evaluate the effects of PM10 on electrocardiogram (ECG) parameters, blood pressure, lipid peroxidation (MDA), xanthine oxidase, and antioxidant enzyme in healthy rats and also to examine the protective effects of vanillic acid (VA) in this respect. Eighty male Wistar rats were divided into eight groups (n = 10), namely control (normal saline, gavage), VAc (10 mg/kg), sham (normal saline, intratracheal instillation), VA (10 mg/kg VA, 10 days gavage +0.1 ml normal saline, intratracheal instillation), PM1 (0.5 mg/kg), PM2 (2.5 mg/kg), PM3 (5 mg/kg), PM3 + VA (5 mg/kg, intratracheal instillation + 10 mg/kg VA, 10 days, gavage) groups. The rats were anesthetized and 0.1 ml of saline as well as a certain concentration of PM10 was instilled into the trachea and it was repeated after 48 h, then 30 min after that, PR interval, QTc, and systolic blood pressure were measured. The activities of antioxidant enzymes, xanthine oxidase (XOX), and malondialdehyde (MDA) were measured in plasma by special Kits. A significant increase in blood pressure (BP), PR interval, QTc, MDA, and XOX and a significant decrease in antioxidant enzyme (CAT, SOD, and GPx) occurred in PM10 groups. Vanillic acid ameliorated blood pressure, QTc, PR interval, XOX, MDA, and increased antioxidant enzymes (SOD, CAT, and GPx) significantly. In the present study, it was shown that PM10 had devastating effects on the heart and blood pressure, probably due to the increased oxidative stress in healthy rats. Vanillic acid could improve the symptoms of PM10 exposure and can be used as an antioxidant agent against the harmful effects of PM10. PMID- 27392622 TI - Spatial and temporal variation of nitrogen concentration and speciation in runoff and storm water in the Indian River watershed, South Florida. AB - Nitrogen (N) is considered as a key element that triggers algal boom in the Indian River Lagoon (IRL), South Florida. Intensive agriculture may have contributed to increased N input into the IRL. Runoff and storm water samples were collected in representative agricultural fields and along waterways that connect lands to the IRL from April 2013 to December 2014. Concentrations of different N species (particulate N, dissolved organic N, dissolved NH4 (+)-N, and NO3 (-)-N) and related water physical-chemical properties were measured. Total N (TN) concentrations generally decreased from agricultural field furrows to discharging point of the waterways but were generally above the US EPA critical level (0.59 mg L(-1)) for surface water. Organic N was the dominant form of dissolved N, followed by NO3 (-)-N, and dissolved NH4 (+)-N. Concentrations and speciation of N in water varied with sites and sampling times but were generally higher in summer and fall and lower in spring and winter, as affected by the seasonality of regional hydrology and agricultural practices. Correlations occurred between N concentration, water physical properties, and rainfall. This information has important implications in the development of best management practices to minimize the impacts of agricultural practice on N loading in the Indian River Lagoon. PMID- 27392623 TI - Influences of plant type on bacterial and archaeal communities in constructed wetland treating polluted river water. AB - Both bacteria and archaeal communities can play important roles in biogeochemical processes in constructed wetland (CW) system. However, the influence of plant type on microbial community in surface water CW remains unclear. The present study investigated bacterial and archaeal communities in five surface water CW systems with different plant species. The abundance, richness, and diversity of both bacterial and archaeal communities considerably differed in these five CW systems. Compared with the other three CW systems, the CW systems planted with Vetiveria zizanioides or Juncus effusus L. showed much higher bacterial abundance but lower archaeal abundance. Bacteria outnumbered archaea in each CW system. Moreover, the CW systems planted with V. zizanioides or J. effusus L. had relatively lower archaeal but higher bacterial richness and diversity. In each CW system, bacterial community displayed much higher richness and diversity than archaeal community. In addition, a remarkable difference of both bacterial and archaeal community structures was observed in the five studied CW systems. Proteobacteria was the most abundant bacterial group (accounting for 33-60 %). Thaumarchaeota organisms (57 %) predominated in archaeal communities in CW systems planted with V. zizanioides or J. effusus L., while Woesearchaeota (23 or 24 %) and Euryarchaeota (23 or 15 %) were the major archaeal groups in CW systems planted with Cyperus papyrus or Canna indica L. Archaeal community in CW planted with Typha orientalis Presl was mainly composed of unclassified archaea. Therefore, plant type exerted a considerable influence on microbial community in surface water CW system. PMID- 27392624 TI - High-VOC biochar-effectiveness of post-treatment measures and potential health risks related to handling and storage. AB - Biochar can contain volatile organic compounds (VOCs), formed and introduced during the pyrolysis process. In some pyrolysis units or under specific conditions during production, pyrolysis vapours can deposit on biochar in significant amounts resulting in high-VOC biochar. In this study, it was tested to which extent VOCs are released from such high-VOC biochars when openly stored, which post-treatment measures are most effective in reducing phytotoxic potential and whether the VOC emissions could exceed human health-related threshold values. It was shown that the initial VOC release of high-VOC biochars can exceed occupational exposure limit values and even after 2 months, the biochars still emitted VOCs exceeding air quality guideline values. Consequently, these specific high-VOC biochars pose health risks when handled or stored openly. Simple open air storage turned out to be insufficient for VOC removal. Low temperature treatment, on the other hand, removed VOCs from the high-VOC biochars effectively and alleviated any human health risks and phytotoxic effects. In addition to the high-VOC biochars, a low-VOC biochar was tested which did not emit any VOCs and was even able to sorb VOCs from the VOC-rich biochar to a certain extent. Thermal treatment and blending with low-VOC biochar are methods which could be used in practise to treat high-VOC biochar, reducing VOC emissions. This study revealed significant new findings on the topic of VOCs in biochar which highlights the need to include VOCs in the list of priority contaminants in biochar. PMID- 27392625 TI - Combining nonthermal plasma with perovskite-like catalyst for NOx storage and reduction. AB - A new NOx storage and reduction (NSR) system is developed for NOx removal by combining perovskite-like catalyst with nonthermal plasma technology. In this hybrid system, catalyst is mainly used for oxidizing NO to NO2 and storing them, while nonthermal plasma is applied as a desorption-reduction step for converting NOx into N2. An innovative catalyst with a high NOx storage capacity and good reduction performance is developed by successive impregnation. The catalysts prepared with various metal oxides were investigated for NOx storage capacity (NSC) and NOx conversion. Characterization of the catalysts prepared reveals that addition of cobalt (Co) and potassium (K) considerably increases the performance for NSC. Results also show that SrKMn0.8Co0.2O4 supported on BaO/Al2O3 has good NSC (209 MUmol/gcatalyst) for the gas stream containing 500 ppm NO and 5 % O2 with N2 as carrier gas. For plasma reduction process, NOx conversion achieved with SrKMn0.8Co0.2O4/BaO/Al2O3 reaches 81 % with the applied voltage of 12 kV and frequency of 6 kHz in the absence of reducing agents. The results indicate that performance of plasma reduction process (81 %) is better than that of thermal reduction (64 %). Additionally, mixed gases including 1 % CO, 1 % H2 and 1 % CH4, and 2 % H2O(g) are simultaneously introduced into the system to investigate the effect on NSR with plasma system and results indicate that performance of NSR with plasma can be enhanced. Overall, the hybrid system is promising to be applied for removing NOx from gas streams. Graphical abstract ?. PMID- 27392626 TI - Spatiotemporal patterns and potential sources of polychlorinated biphenyl (PCB) contamination in Scots pine (Pinus sylvestris) needles from Europe. AB - Using pine needles as a bio-sampler of atmospheric contamination is a relatively cheap and easy method, particularly for remote sites. Therefore, pine needles have been used to monitor a range of semi-volatile contaminants in the air. In the present study, pine needles were used to monitor polychlorinated biphenyls (PCBs) in the air at sites with different land use types in Sweden (SW), Czech Republic (CZ), and Slovakia (SK). Spatiotemporal patterns in levels and congener profiles were investigated. Multivariate analysis was used to aid source identification. A comparison was also made between the profile of indicator PCBs (ind-PCBs-PCBs 28, 52, 101, 138, 153, and 180) in pine needles and those in active and passive air samplers. Concentrations in pine needles were 220-5100 ng kg(-1) (?18PCBs - ind-PCBs and dioxin-like PCBs (dl-PCBs)) and 0.045-1.7 ng toxic equivalent (TEQ) kg(-1) (dry weight (dw)). Thermal sources (e.g., waste incineration) were identified as important sources of PCBs in pine needles. Comparison of profiles in pine needles to active and passive air samplers showed a lesser contribution of lower molecular weight PCBs 28 and 52, as well as a greater contribution of higher molecular weight PCBs (e.g., 180) in pine needles. The dissimilarities in congener profiles were attributed to faster degradation of lower chlorinated congeners from the leaf surface or metabolism by the plant. PMID- 27392629 TI - Trajectories of river chemical quality issues over the Longue Duree: the Seine River (1900S-2010). AB - River quality trajectories are presented for (i) organic pollution, (ii) eutrophication, (iii) nitrate pollution, and (iv) metal contamination over the Longue Duree (130 to 70 years). They are defined by a quantified state indicator (S) specific to each issue, compared to drivers (D) or pressures (P) and to social responses (R) that reflect the complex interactions between society and river quality. The Lower Seine River, naturally sensitive to anthropogenic pressures, greatly impacted by Paris urban growth, industrialization, and intensive agriculture, and well documented by the PIREN-Seine 25-year research program, was chosen to illustrate these trajectories. State indicators, dissolved oxygen, algal pigments, nitrate, and heavy metals (Cd, Cr, Hg, Pb, Zn) in sediments have only been monitored by river basin authorities since 1971. Therefore, their past changes have been reconstructed using three approaches: (i) reassessment of historical sources, (ii) pressure-state models that reconstruct past water quality, and (iii) sedimentary archives of past persistent contamination from dated floodplain cores. The indicators were then transformed into river quality status using contemporary water quality criteria throughout these records. Each environmental issue shows specific trajectories because each has its own relationship between the issue evidence and the social response, but all are characterized by very poor quality in the past, largely ignored: the long term summer hypoxia (<1880-1995), the summer eutrophication peak (1965-2005), the growing nitrate level since the 1950s, recently stabilized but still high, and the extreme metal contamination (>1935-2000) that peaked in the 1960s. The efficiency of social responses has been highly variable but more efficient in the last 15-25 years. PMID- 27392627 TI - Increased copper bioremediation ability of new transgenic and adapted Saccharomyces cerevisiae strains. AB - Environmental pollution with heavy metals is a very serious ecological problem, which can be solved by bioremediation of metal ions by microorganisms. Yeast cells, especially Saccharomyces cerevisiae, are known to exhibit a good natural ability to remove heavy metal ions from an aqueous phase. In the present work, an attempt was made to increase the copper-binding properties of S. cerevisiae. For this purpose, new strains of S. cerevisiae were produced by construction and integration of recombinant human MT2 and GFP-hMT2 genes into yeast cells. The ySA4001 strain expressed GFP-hMT2p under the constitutive pADH1 promoter and the ySA4002 and ySA4003 strains expressed hMT2 and GFP-hMT2 under the inducible pCUP1 promoter. An additional yMNWTA01 strain was obtained by adaptation of the BY4743 wild type S. cerevisiae strain to high copper concentrations. The yMNWTA01, ySA4002, and ySA4003 strains exhibited an enhanced ability for copper ion bioremediation. PMID- 27392628 TI - Treatment of an industrial stream containing vinylcyclohexene by the H2O2/UV process. AB - Petrochemical industries generate wastewaters containing pollutants that can severely impact the biological treatment systems. Some streams from specific production units may contain nonbiodegradable or toxic compounds that impair the performance of the wastewater treatment plant and should be segregated and treated by specific techniques. In this work, the utilization of chemical oxidation (H2O2/UV) was investigated for removing 4-vinylcyclohexene (VCH) from a liquid stream coming from the production of hydroxylated liquid polybutadiene (HLPB). Besides VCH, this stream also contains ethanol, hydrogen peroxide, and many other organic compounds. Experiments were carried out in a small-scale photochemical reactor (0.7 L) using a 25-W low-pressure mercury vapor lamp. The photochemical reactor was operated in batch, and the reaction times were comprised between 10 and 60 min. Assays were also performed with a synthetic medium containing VCH, H2O2, and ethanol to investigate the removal of these substances in a less complex aqueous matrix. By-products formed in the reaction were identified by gas chromatography and mass spectroscopy (GC-MS). VCH was significantly removed by the oxidation process, in most assays to undetectable levels. Ethanol removal varied from 16 to 23 % depending on the reaction conditions. Acetic acid, acetaldehyde, and diols were detected as by-products of the industrial wastewater stream oxidation. A drop on the toxicity of the industrial stream was also observed in assays using the organism Artemia salina. PMID- 27392630 TI - Heavy metal contamination status and source apportionment in sediments of Songhua River Harbin region, Northeast China. AB - The Songhua River represents one of the seven major river systems in China. It flows through Harbin city with 66 km long, locating in the northern China with a longer winter time. This paper aimed to study concentration distributions, stability, risk assessment, and source apportionment of heavy metals including chromium (Cr), cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), copper (Cu), zinc (Zn), and nickel (Ni) in 11 selected sections of the Songhua River Harbin region. Results showed that Cr, Cd, Pb, Hg, and As exceeded their respective geochemical background values in sediments of most monitoring sections. Compared with other important rivers and lakes in China, Cr, Hg, Cd, and As pollutions in surface sediments were above medium level. Further analysis of chemical speciation indicated that Cr and As in surface sediments were relatively stable while Pb and Cd were easily bioavailable. Correlation analysis revealed sources of these metals except As might be identical. Pollution levels and ecological risks of heavy metals in surface sediments presented higher in the mainstream region (45 degrees 47.0' N ~ 45 degrees 53.3' N, 126 degrees 37.0' E ~ 126 degrees 42.1' E). Source apportionment found Hejiagou and Ashi River were the main contributors to metal pollution of this region. Thus, anthropogenic activities along the Hejiagou and Ashi River should be restricted in order to protect the Songhua River Harbin region from metal contamination. PMID- 27392632 TI - Kynurenine pathway metabolism and the microbiota-gut-brain axis. AB - It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. PMID- 27392631 TI - Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB/c mice: the role of cortical BDNF, microRNA-212, and MeCP2. AB - RATIONALE: Early life stress is a major risk factor for cocaine addiction; however, the underlying molecular mechanisms remain relatively unexplored. MicroRNA-212 (miR-212) and methyl CpG binding protein 2 (MeCP2) have recently emerged as key regulators of brain-derived neurotrophic factor (BDNF) signaling during the acquisition and maintenance of cocaine-seeking behaviors. OBJECTIVES: We therefore investigated the effect of maternal separation (MS) on cocaine induced conditioned place preference (CPP) during periadolescence and how this influences miR-212, Mecp2, and Bdnf expressions in the prefrontal cortex. METHODS: Male BALB/c mice subjected to MS (3 h/day) from postnatal day 2 to 15 or normal animal facility rearing (AFR) were tested for CPP at postnatal day 45, or not exposed to experimental manipulations (drug-naive animals). Cultured primary cortical neurons were used to determine miR-212 expression changes following depolarization by KCL treatment. RESULTS: MS increased cocaine-induced CPP and decreased Bdnf exon IV expression, which correlated with higher CPP scores in such animals. An experience-dependent decrease in miR-212 expression was observed following CPP test. This effect was mimicked in primary cortical neurons in vitro, under activity-dependent conditions. In contrast, increased Mecp2 expression was found after CPP test, suggesting an opposing relationship between miR-212 and Mecp2 expression following cocaine place preference acquisition. However, these effects were not present in mice exposed to MS. CONCLUSIONS: Together, our results suggest that early life stress can enhance the motivational salience for cocaine-paired cues during periadolescence, and that altered expression of miR-212, Mecp2, and Bdnf in the prefrontal cortex is involved in this process. PMID- 27392633 TI - Emerging roles for the novel estrogen-sensing receptor GPER1 in the CNS. AB - Estrogens play a key role in regulating reproductive and neuroendocrine function by activating classical nuclear steroid receptors that act as ligand gated transcription factors. However evidence is growing that estrogens also promote rapid non-genomic responses via activation of membrane-associated estrogen receptors. The G protein-coupled estrogen receptor (GPER1; also known as GPR30) has been identified as one of the main estrogen-sensitive receptors responsible for the rapid non-genomic actions of estrogen. In recent years, our understanding of the CNS actions of GPER1s has significantly increased following the development of selective pharmacological tools and via the use of transgenic technologies to knockout GPER1 in mice. Here we review recent advances that have been made to uncover the role of GPER1s in the CNS. This article is part of the Special Issue entitled 'Lipid Sensing G Protein-Coupled Receptors in the CNS'. PMID- 27392634 TI - Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery. AB - Allosteric modulators, that exhibit no intrinsic agonist activity, offer the advantage of spatial and temporal fine-tuning of endogenous agonist activity, allowing the potential for increased selectivity, reduced adverse effects and improved clinical outcomes. Some allosteric ligands can differentially activate and/or modulate distinct signaling pathways arising from the same receptor, phenomena referred to as 'biased agonism' and 'biased modulation'. Emerging evidence for CNS disorders with glutamatergic dysfunction suggests the metabotropic glutamate receptor subtype 5 (mGlu5) is a promising target. Current mGlu5 allosteric modulators have largely been classified based on modulation of intracellular calcium (iCa2+) responses to orthosteric agonists alone. We assessed eight mGlu5 allosteric modulators previously classified as mGlu5 PAMs or PAM-agonists representing four distinct chemotypes across multiple measures of receptor activity, to explore their potential for engendering biased agonism and/or modulation. Relative to the reference orthosteric agonist, DHPG, the eight allosteric ligands exhibited distinct biased agonism fingerprints for iCa2+ mobilization, IP1 accumulation and ERK1/2 phosphorylation in HEK293A cells stably expressing mGlu5 and in cortical neuron cultures. VU0424465, DPFE and VU0409551 displayed the most disparate biased signaling fingerprints in both HEK293A cells and cortical neurons that may account for the marked differences observed previously for these ligands in vivo. Select mGlu5 allosteric ligands also showed 'probe dependence' with respect to their cooperativity with different orthosteric agonists, as well as biased modulation for the magnitude of positive cooperativity observed. Unappreciated biased agonism and modulation may contribute to unanticipated effects (both therapeutic and adverse) when translating from recombinant systems to preclinical models. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. PMID- 27392636 TI - Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe-Based Single Nucleotide Polymorphism Array. AB - Gene copy number aberrations (CNAs) represent a major class of cancer-related genomic alterations that drive solid tumors. Comprehensive and sensitive detection of CNAs is challenging because of often low quality and quantity of DNA isolated from the formalin-fixed, paraffin-embedded (FFPE) solid tumor samples. Here, in a clinical molecular diagnostic laboratory, we tested the utility and validated a molecular inversion probe-based (MIP) array to routinely screen for CNAs in solid tumors. Using low-input FFPE DNA, the array detects genome-wide CNAs with a special focus on 900 cancer-related genes. A cohort of 76 solid tumors of various types and tumor cellularity (20% to 100%), and four cancer cell lines were used. These harbored CNAs in clinically important genes (ERBB2, EGFR, FGFR1, KRAS, MYC) as detected by orthogonal techniques like next-generation sequencing or fluorescence in situ hybridization. Results of the MIP array were concordant with results from orthogonal techniques, and also provided additional information regarding the allelic nature of the CNAs. Limit-of-detection and assay reproducibility studies showed a high degree of sensitivity and reproducibility of detection, respectively. FFPE compatibility, ability to detect CNAs with high sensitivity, accuracy, and provide valuable information such as loss of heterozygosity along with relatively short turnaround times makes the MIP array a desirable clinical platform for routine screening of solid tumors in a clinical laboratory. PMID- 27392635 TI - The clobazam metabolite N-desmethyl clobazam is an alpha2 preferring benzodiazepine with an improved therapeutic window for antihyperalgesia. AB - Data from genetically modified mice suggest that benzodiazepine (BDZ)-site agonists with improved selectivity for alpha2-subtype GABAA receptors (alpha2GABAAR) are potentially useful for the treatment of neuropathic pain. Subtype-selective compounds available for preclinical tests in rodents support this concept but have not been approved for human use, hindering proof-of-concept studies in patients. We recently proposed that N-desmethyl clobazam (NDMC), the main metabolite of the licensed BDZ clobazam (CBZ), is responsible for most of the antihyperalgesia observed in mice after CBZ administration. In order to assess a potentially favorable pharmacological profile of NDMC, we analyzed differences in the GABAAR subtype specificity of CBZ, NDMC and diazepam (DZP) in recombinant receptors. DZP and CBZ potentiated sedating alpha1GABAARs and antihyperalgesic alpha2GABAARs with similar efficacies, whereas NDMC preferred alpha2GABAARs over alpha1GABAARs across a wide concentration range. In vivo, DZP and NDMC reduced neuropathic pain at doses between 3 and 30 mg/kg. At these doses, DZP had strong locomotor sedating effects while NDMC caused no or only weak sedation. Sedative effects of NDMC became apparent when the action of NDMC was restricted to alpha1GABAARs. However, when GABAAR point-mutated mice were studied that allow the analysis of antihyperalgesia and sedation in isolation, we found that, compared to DZP, NDMC had a significantly improved therapeutic window, consistent with its more favorable alpha2/alpha1 in vitro activity ratio. Given that NDMC should share the safety profile of its parent compound CBZ, it should be well-suited for proof-of-concept studies in human volunteers or patients. PMID- 27392637 TI - The role of sulfated steroid hormones in reproductive processes. AB - Sulfated steroid hormones, such as dehydroepiandrosterone sulfate or estrone-3 sulfate, have long been regarded as inactive metabolites as they cannot activate classical steroid receptors. Some of them are present in the blood circulation at quite high concentrations, but generally sulfated steroids exhibit low membrane permeation due to their hydrophilic properties. However, sulfated steroid hormones can actively be imported into specific target cells via uptake carriers, such as the sodium-dependent organic anion transporter SOAT, and, after hydrolysis by the steroid sulfatase (so-called sulfatase pathway), contribute to the overall regulation of steroid responsive organs. To investigate the biological significance of sulfated steroid hormones for reproductive processes in humans and animals, the research group "Sulfated Steroids in Reproduction" was established by the German Research Foundation DFG (FOR1369). Projects of this group deal with transport of sulfated steroids, sulfation of free steroids, desulfation by the steroid sulfatase, effects of sulfated steroids on steroid biosynthesis and membrane receptors as well as MS-based profiling of sulfated steroids in biological samples. This review and concept paper presents key findings from all these projects and provides a broad overview over the current research on sulfated steroid hormones in the field of reproduction. PMID- 27392638 TI - Management of Disconnected Pancreatic Duct Syndrome. AB - OPINION STATEMENT: A disconnected pancreatic duct most commonly follows an episode of severe pancreatitis and walled-off necrosis (WON). When the latter is drained percutaneously, a pancreatic fistula connected to an upstream and disconnected duct is commonly seen. Transgastric drainage of WON with or without concomitant percutaneous drainage (dual drainage) will allow placement of two pigtail stents to drain the upstream duct and ultimately allows removal of percutaneous tubes and avoids the need for distal pancreatectomy. These stents should be left in place indefinitely. In patients referred with percutaneous drains and a disconnected pancreatic duct but without a concomitant fluid collection, a combined procedure, in which an interventional radiologist places a TIPS needle into the drain tract to puncture the stomach, allows the endoscopist access to dilate and stent the tract in a manner comparable to pseudocyst drainage. These stents should be left indefinitely, unless subsequent imaging demonstrates atrophy of the disconnected pancreatic tail. PMID- 27392639 TI - Nuclear transit study in children with chronic faecal soiling after Hirschsprung disease (HSCR) surgery has revealed a group with rapid proximal colonic treatment and possible adverse reactions to food. AB - BACKGROUND/PURPOSE: Long-term problems with faecal incontinence occur in up to 50 % of patients after pull-through for Hirschsprung disease (HSCR). The cause often remains unknown, leading to empirical treatments. Using nuclear transit study, we found some patients surprisingly had rapid proximal colonic transit, suspicious of occult diarrhoea. We aimed to assess whether these patients had unrecognized adverse reactions to food. METHODS: Patients (n = 10, all males, 9.6 year; 4.25 15.5 years) with persistent faecal incontinence following pull-through for HSCR referred to the senior author and after exclusion of anatomical defects, underwent nuclear transit studies. Most (8) subsequently underwent breath hydrogen tests for sugar malabsorption and were tested for adverse reactions to food. Exclusion diets for protein allergens, lactose or fructose were then trialed. RESULTS: Of the 10 patients with rapid intestinal transit proven on nuclear transit study, breath hydrogen tests for fructose and/or lactose malabsorption were done in 8, and were positive in 7/8 patients. Exclusion diets contributed to either resolution or improvement in faecal incontinence in 9/10 patients. CONCLUSIONS: Rapid transit in the proximal, ganglionated colon may be present in children with faecal incontinence following pull-through for HSCR, possibly secondary to adverse reactions to food. This study suggests that children with post-operative soiling may benefit from a transit study and hydrogen breath tests to diagnose adverse reactions to food caused by sugar malabsorption. PMID- 27392640 TI - Role of ventral pallidal D2 dopamine receptors in the consolidation of spatial memory. AB - The role of dopamine (DA) receptors in spatial memory consolidation has been demonstrated in numerous brain regions, among others in the nucleus accumbens which innervates the ventral pallidum (VP). The VP contains both D1 and D2 DA receptors. We have recently shown that the VP D1 DA receptor activation facilitates consolidation of spatial memory in Morris water maze test. In the present study, the role of VP D2 DA receptors was investigated in the same paradigm. In the first experiment, the D2 DA receptor agonist quinpirole was administered into the VP of male Wistar rats in three doses (0.1, 1.0 or 5.0MUg, respectively in 0.4MUl physiological saline). In the second experiment, the D2 DA receptor antagonist sulpiride was applied to elucidate whether it can antagonise the effects of quinpirole. The antagonist (4.0MUg, dissolved in 0.4MUl physiological saline) was microinjected into the VP either by itself or prior to 1.0MUg agonist treatment. Control animals received saline in both experiments. The two higher doses (1.0 and 5.0MUg) of the agonist accelerated memory consolidation relative to controls and increased the stability of the consolidated memory against extinction. Sulpiride pretreatment antagonised the effects of quinpirole. In addition, the antagonist microinjected into the VP immediately after the second conditioning trial impaired learning functions. The present data provide evidences for the important role of VP D2 DA receptors in the consolidation and stabilization of spatial memory. PMID- 27392642 TI - Sensitivity to trauma-associated cues is restricted to vulnerable traumatized rats and reinstated after extinction by yohimbine. AB - While post-traumatic stress disorder (PTSD) symptom is mainly characterized by re experiencing the traumatic event, the reactivity to trauma-associated cues in resilient and vulnerable subjects has not been extensively studied. Using an animal model of PTSD induced by a single prolonged stress (SPS), the responses of traumatized Vulnerable and Resilient rats to PTSD-like symptom tests and to trauma-associated cues were investigated. In addition, the implication of the noradrenergic system in "re-experiencing" was explored. Rats received either a SPS, combining a 2h restraint stress, a 20min forced-swim followed by a 15min rest, and a loss of consciousness produced by inhaling CO2 emissions, delivered in the presence of particular cues (tone and odor), or a control procedure. PTSD like symptoms and reactivity to various trauma-associated cues (specific, contextual, or predictive) were tested from D15 to D60 after the SPS. Rats were then divided into Resilient and Vulnerable on the basis of three main symptom tests, including the elevated plus maze, the light-dark and the acoustic startle response tests. Although Resilient rats behaved like Controls rats, Vulnerable rats developed long-term PTSD-like symptoms on the main symptoms tests (anxiety and alteration of arousal), as well as other PTSD-like outcomes (such as anhedonia and avoidance to trauma-associated cues). These Vulnerable rats were also the only ones to demonstrate strong reactivity to trauma-associated cues. In addition, the alpha-2 adrenergic receptor antagonist, Yohimbine (i.p., 1.5mg/kg/ml), was able to reinstate fear responses to an extinguished trauma associated odor. Our results established clear relationships between Vulnerability to trauma and reactivity to trauma-associated cues and further suggest an involvement of the noradrenergic system. PMID- 27392641 TI - Forelimb training drives transient map reorganization in ipsilateral motor cortex. AB - Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. PMID- 27392644 TI - Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals. AB - The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results. PMID- 27392643 TI - Characterization of irritans mariner-like elements in the olive fruit fly Bactrocera oleae (Diptera: Tephritidae): evolutionary implications. AB - Genomic variation among species is commonly driven by transposable element (TE) invasion; thus, the pattern of TEs in a genome allows drawing an evolutionary history of the studied species. This paper reports in vitro and in silico detection and characterization of irritans mariner-like elements (MLEs) in the genome and transcriptome of Bactrocera oleae (Rossi) (Diptera: Tephritidae). Eleven irritans MLE sequences have been isolated in vitro using terminal inverted repeats (TIRs) as primers, and 215 have been extracted in silico from the sequenced genome of B. oleae. Additionally, the sequenced genomes of Bactrocera tryoni (Froggatt) and Bactrocera cucurbitae (Diptera: Tephritidae) have been explored to identify irritans MLEs. A total of 129 sequences from B. tryoni have been extracted, while the genome of B. cucurbitae appears probably devoid of irritans MLEs. All detected irritans MLEs are defective due to several mutations and are clustered together in a monophyletic group suggesting a common ancestor. The evolutionary history and dynamics of these TEs are discussed in relation with the phylogenetic distribution of their hosts. The knowledge on the structure, distribution, dynamic, and evolution of irritans MLEs in Bactrocera species contributes to the understanding of both their evolutionary history and the invasion history of their hosts. This could also be the basis for genetic control strategies using transposable elements. PMID- 27392645 TI - Developing a data element repository to support EHR-driven phenotype algorithm authoring and execution. AB - The Quality Data Model (QDM) is an information model developed by the National Quality Forum for representing electronic health record (EHR)-based electronic clinical quality measures (eCQMs). In conjunction with the HL7 Health Quality Measures Format (HQMF), QDM contains core elements that make it a promising model for representing EHR-driven phenotype algorithms for clinical research. However, the current QDM specification is available only as descriptive documents suitable for human readability and interpretation, but not for machine consumption. The objective of the present study is to develop and evaluate a data element repository (DER) for providing machine-readable QDM data element service APIs to support phenotype algorithm authoring and execution. We used the ISO/IEC 11179 metadata standard to capture the structure for each data element, and leverage Semantic Web technologies to facilitate semantic representation of these metadata. We observed there are a number of underspecified areas in the QDM, including the lack of model constraints and pre-defined value sets. We propose a harmonization with the models developed in HL7 Fast Healthcare Interoperability Resources (FHIR) and Clinical Information Modeling Initiatives (CIMI) to enhance the QDM specification and enable the extensibility and better coverage of the DER. We also compared the DER with the existing QDM implementation utilized within the Measure Authoring Tool (MAT) to demonstrate the scalability and extensibility of our DER-based approach. PMID- 27392646 TI - A cloud-based mobile system to improve respiratory therapy services at home. AB - Chronic respiratory diseases are one of the most prevalent health problems in the world. Treatment for these kind of afflictions often take place at home, where the continuous care of a medical specialist is frequently beyond the economical means of the patient, therefore having to rely on informal caregivers (family, friends, etc.). Unfortunately, these treatments require a deep involvement on their part, which results in a heavy burden on the caregivers' routine and usually end up deteriorating their quality of life. In recent years, mHealth and eHealth applications have gained a wide interest in academia due to new capabilities enabled by the latest advancements in mobile technologies and wireless communication infrastructure. These innovations have resulted in several applications that have successfully managed to improve automatic patient monitoring and treatment and to bridge the distance between patients, caregivers and medical specialists. We therefore seek to move this trend forward by now pushing these capabilities into the field of respiratory therapies in order to assist patients with chronic respiratory diseases with their treatment, and to improve both their own and their caregivers' quality of life. This paper presents a cloud-based mobile system to support and improve homecare for respiratory diseases. The platform described uses vital signs monitoring as a way of sharing data between hospitals, caregivers and patients. Using an iterative research approach and the user's direct feedback, we show how mobile technologies can improve a respiratory therapy and a family's quality of life. PMID- 27392647 TI - Dynamic detection of window starting positions and its implementation within an activity recognition framework. AB - Activity recognition is an intrinsic component of many pervasive computing and ambient intelligent solutions. This has been facilitated by an explosion of technological developments in the area of wireless sensor network, wearable and mobile computing. Yet, delivering robust activity recognition, which could be deployed at scale in a real world environment, still remains an active research challenge. Much of the existing literature to date has focused on applying machine learning techniques to pre-segmented data collected in controlled laboratory environments. Whilst this approach can provide valuable ground truth information from which to build recognition models, these techniques often do not function well when implemented in near real time applications. This paper presents the application of a multivariate online change detection algorithm to dynamically detect the starting position of windows for the purposes of activity recognition. PMID- 27392649 TI - The Impact of Minimally Invasive Surgery on Major Iatrogenic Ureteral Injury and Subsequent Ureteral Repair During Hysterectomy: A National Analysis of Risk Factors and Outcomes. AB - OBJECTIVE: To identify risk factors for ureteral injury during hysterectomy and to assess outcomes of concurrent minimally invasive vs converted to open repairs. METHODS: We queried the American College of Surgeons-National Surgical Quality Improvement Program database between 2005 and 2013 to identify abdominal hysterectomy (AH), minimally invasive hysterectomy (MIH), or vaginal hysterectomy. Ureteral injury was identified based on intraoperative or delayed management. Multivariate logistic regression was performed to assess the effect of hysterectomy approach on risk of ureteral injury while controlling for covariates. For patients with ureteral injury during MIH, we compared 30-day outcomes following minimally invasive vs converted open repairs. RESULTS: There were 302 iatrogenic ureteral injuries from 96,538 hysterectomies, with 0.18%, 0.48%, and 0.04% from AH, MIH, and vaginal hysterectomy, respectively. Patients who underwent MIH were younger and had decreased comorbidities compared to patients who underwent AH (all P < .001). MIH resulted in lower overall complications (6.6% vs 14.8%, P < .001) but higher ureteral injury rate (0.48% vs 0.18%, P < .001) compared to AH. On multivariate analysis, the minimally invasive approach was associated with increased risk of ureteral injury (odds ratio 4.2, P < .001). Patients undergoing minimally invasive ureteral repairs (89%) during MIH had shorter operating room time and length of stay but similar overall perioperative complications compared to those with converted open repairs (11%). CONCLUSION: Using a large national series, we show that the minimally invasive approach for hysterectomy is an independent risk factor for iatrogenic ureteral injuries. During MIH, concurrent minimally invasive ureteral repairs resulted in comparable 30-day outcomes compared to converted to open repairs. PMID- 27392650 TI - A "Needling" Complication. AB - Intracavernosal injection therapy with vasoactive agents for treatment of erectile dysfunction has been around for more than 3 decades since its advent in the early 1980s. Common complications include ecchymosis and hematoma at the site of injection, priapism, and fibrosis. We describe a rare but potentially dangerous complication of breakage of needle during administering of injections, and discuss its successful retrieval. PMID- 27392648 TI - Prospects for chimeric antigen receptor (CAR) gammadelta T cells: A potential game changer for adoptive T cell cancer immunotherapy. AB - Excitement is growing for therapies that harness the power of patients' immune systems to combat their diseases. One approach to immunotherapy involves engineering patients' own T cells to express a chimeric antigen receptor (CAR) to treat advanced cancers, particularly those refractory to conventional therapeutic agents. Although these engineered immune cells have made remarkable strides in the treatment of patients with certain hematologic malignancies, success with solid tumors has been limited, probably due to immunosuppressive mechanisms in the tumor niche. In nearly all studies to date, T cells bearing alphabeta receptors have been used to generate CAR T cells. In this review, we highlight biological characteristics of gammadelta T cells that are distinct from those of alphabeta T cells, including homing to epithelial and mucosal tissues and unique functions such as direct antigen recognition, lack of alloreactivity, and ability to present antigens. We offer our perspective that these features make gammadelta T cells promising for use in cellular therapy against several types of solid tumors, including melanoma and gastrointestinal cancers. Engineered gammadelta T cells should be considered as a new platform for adoptive T cell cancer therapy for mucosal tumors. PMID- 27392651 TI - Preoperative Frailty Is Associated With Discharge to Skilled or Assisted Living Facilities After Urologic Procedures of Varying Complexity. AB - OBJECTIVE: To evaluate the association between frailty and postoperative discharge destination after different types of commonly performed urologic procedures in older patients. MATERIALS AND METHODS: Using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2011 to 2013, we identified commonly performed inpatient urologic procedures among patients aged 65 and older. We then assessed the effect of frailty, measured by the NSQIP Frailty Index (NSQIP-FI), on discharge to a skilled or assisted living facility using logistic regression and assessed the heterogeneity of this effect across procedures using 2-level random effects modeling. RESULTS: Overall, 1144 out of 20,794 (5.5%) urologic cases, representing 19 different procedures, resulted in discharge to a skilled or assisted living facility. Cystectomy and large transurethral resection of bladder tumor had the highest percentage (16.3%). Twenty-five percent of patients undergoing urology procedures were frail (NSQIP-FI 0.18+), including 9.8% of patients discharged to a facility. Even after adjustment for year, age, race, type of anesthesia, smoking status, recent weight loss, and whether or not the procedure was elective, frailty was strongly associated with discharge to a facility (adjusted odds ratio 3.1 [96% confidence interval 2.5, 3.8] for NSQIP-FI 0.18+ compared to NSQIP FI 0). This finding was consistent across most procedures of varying complexity with an overall effect of odds ratio 1.6 (95% confidence interval 1.5, 2.0). CONCLUSION: Increasing frailty is associated with discharge to a skilled or assisted living facility across most inpatient urologic procedures evaluated, regardless of complexity. This information is important for preoperative counseling with patients undergoing urologic surgery. PMID- 27392652 TI - The Association Between Evaluation at Academic Centers and the Likelihood of Expectant Management in Low-risk Prostate Cancer. AB - OBJECTIVE: To identify factors associated with expectant management (EM) in a large cohort of men with low-risk prostate cancer based on cancer center type (community vs academic). EM, consisting of active surveillance or observation for men with low-risk prostate cancer, is an increasingly recognized management option, given the morbidity and lack of a survival benefit associated with definitive treatment. However, the influence of cancer center type on treatment selection is uncertain. MATERIALS AND METHODS: We performed a retrospective analysis of the National Cancer Data Base from 2010 to 2013. Men with low-risk prostate cancer were divided by management strategy into groups consisting of EM or definitive treatment. The association between management strategy and facility type (community vs academic) was characterized using 2-level hierarchical mixed effects logistic regression models. RESULTS: There were 52,417 (57%) men evaluated at community centers and 39,139 men (43%) evaluated at academic centers. Patients evaluated at academic centers were significantly more likely to receive EM than those at community centers (17% vs 8%, P < .001). After adjusting for pertinent covariates, evaluation at an academic vs community facility was independently associated with increased odds of EM utilization (adjusted odds ratio 2.70, 95% confidence interval 2.00-3.66). Fifty-one percent of the total variance was explained by interfacility variation. CONCLUSION: The likelihood of receiving EM for low-risk prostate cancer was significantly lower in men evaluated at community centers. Further investigation is warranted to elucidate factors that influence the management of low-risk prostate cancer, including individual treatment center patterns. PMID- 27392653 TI - Predictors of Comfort and Confidence Among Medical Students in Providing Care to Patients at Risk of Suicide. AB - OBJECTIVE: The aim of this study was to identify factors associated with comfort and confidence in providing care to patients at risk of suicide, in a sample of Australian medical students. METHODS: An online cross-sectional survey was completed by 116 current medical students (42 % male) aged between 20 and 41 years (M = 25, SD = 3.8). RESULTS: Greater personal experience of suicide and previous contact with patients with psychiatric problems were significantly associated with both increased perceived comfort and increased confidence in providing care for individuals with suicidal thoughts or behaviors, based on self report. However, these effects may not reflect objective measures of competency and additional research is needed to assess generalizability of the findings due to the sampling method. CONCLUSIONS: Increasing medical student contact with patients at risk of suicide through the implementation of psychiatry placements, gateway programs, and early year exposure to patients with psychiatric problems may increase perceived confidence and comfort in providing care to individuals at risk of suicide. Further research should evaluate the impact of such programs on behavioral indices of clinical competency. PMID- 27392654 TI - Genome-scale comparison of expanded gene families in Plasmodium ovale wallikeri and Plasmodium ovale curtisi with Plasmodium malariae and with other Plasmodium species. AB - Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status. PMID- 27392655 TI - Outcome and features of acute kidney injury complicating hypoxic hepatitis at the medical intensive care unit. AB - BACKGROUND: Hypoxic hepatitis (HH) is a frequent and potentially life-threatening event typically occurring in critically ill patients as a consequence of hemodynamic impairment. While acute kidney injury (AKI) has been well described in patients with acute liver failure, incidence and outcome of AKI accompanying HH are unclear. The aim of this study was to assess incidence, clinical implications and outcome of AKI and renal replacement therapy (RRT) in critically ill patients with HH. METHODS: A total of 1948 consecutive critically ill admissions were studied at the Medical University of Vienna. Laboratory and clinical parameters as well as the presence of HH and AKI were assessed on a daily basis. Outcome, renal recovery and length of stay were assessed and documented, and patients were followed for 1 year. RESULTS: A total of 295 admissions (15 %) developed HH. Main precipitators were cardiogenic (44 %) and septic shock (36 %). Occurrence of HH was significantly associated with AKI [OR 4.50 (95 % CI 3.30-6.12)] and necessity of renal replacement therapy [RRT; OR 3.36 (95 % CI 2.58-4.37)], p < 0.001 for both. Two hundred forty admissions with HH (81 %) developed AKI, 159 of whom (66 %) had AKI stage 3. Both HH and AKI were significantly linked to mortality. AKI stage 3, international normalized ratio (INR, during HH) and the presence of septic shock were identified as independent predictors of 28-day mortality in admissions with HH, whereas RRT was identified as an independent protective factor. There was a synergistic effect of HH and AKI on length of stay at the ICU. Of all HH survivors treated with RRT, 71 % showed renal recovery during follow-up. CONCLUSION: HH is frequently complicated by occurrence of AKI. Severity of HH, AKI stage and the presence of septic shock seem to contribute to poor outcome in these patients. Initiation of RRT in HH with AKI may enable renal recovery and should not be withheld in medical ICU patients. PMID- 27392656 TI - [Not Available]. AB - In order to evaluate the attractiveness of France for conducting international clinical trials, a survey is performed every two years among pharmaceutical companies that are based in France or have affiliates in France. Nineteen companies (61.9 % of the French market) have participated in the current survey which included 385 international phase II and III clinical studies, 77 countries, 29,708 centres and 312,835 patients (included in 2006/2007). France (400 patients/million inhabitants) ranked among the best European recruiters in second position behind Scandinavia. Since 2006, France has improved administrative processes and reduced deadlines for hospital contracts. Protocols are now to be given the go-ahead by French Authorities (Afssaps and CPP) within 60 days, in accordance with European directive. Its performance in early phases, oncology/hematology and vaccines/anti-infectious contribute to the attractiveness of France in international clinical research. PMID- 27392657 TI - [Not Available]. PMID- 27392658 TI - [Not Available]. PMID- 27392659 TI - Corrigendum to "development, implementation and evaluation of a mental rehearsal strategy to improve clinical performance and reduce stress: A mixed methods study" [Nurse Educ. Today 37 (2016) 27-32]. PMID- 27392660 TI - Evaluating the efficiency of desflurane reflection in two commercially available reflectors. AB - With the AnaConDaTM and the MIRUSTM system, volatile anesthetics can be administered for inhalation sedation in intensive care units. Instead of a circle system, both devices use anesthetic reflectors to save on the anesthetic agent. We studied the efficiency of desflurane reflection with both devices using different tidal volumes (VT), respiratory rates (RR), and 'patient' concentrations (CPat) in a bench study. A test lung was ventilated with four settings (volume control, RR * VT: 10 * 300 mL, 10 * 500 mL, 20 * 500 mL, 10 * 1000 mL). Two different methods for determination of reflection efficiency were established: First (steady state), a bypass flow carried desflurane into the test lung (flowin), the input concentration (Cin) was varied (1-17 vol%), and the same flow (flowex, Cex) was suctioned from the test lung. After equilibration, CPat was stored online and averaged; efficiency [%] was calculated [Formula: see text]. Second (washout), flowin and flowex were stopped, the decline of CPat was measured; efficiency was calculated from the decay constant of the exponential regression equation. Both measurement methods yielded similar results (Bland Altman: bias: -0.9 %, accuracy: +/-5.55 %). Efficiencies higher than 80 % (>80 % of molecules exhaled are reflected) could be demonstrated in the clinical range of CPat and VT. Efficiency inversely correlates with the product of CPat and VT which can be imagined as the volume of anesthetic vapor exhaled by the patient in one breath, but not with the respiratory frequency. Efficiency of the AnaConDaTM was higher for each setting compared with the MIRUSTM. Desflurane is reflected by both reflectors with efficiencies high enough for clinical use. PMID- 27392661 TI - Should Children Be Given Priority in Kidney Allocation? AB - Kidneys for transplantation are scarce, and many countries give priority to children in allocating them. This paper explains and criticizes the paediatric priority. We set out the relevant ethical principles of allocation, such as utility and severity, and the relevant facts to do with such matters as sensitization and child development. We argue that the facts and principles do not support and sometimes conflict with the priority given to children. We next consider various views on how age or the status of children should affect allocation. Again, these views do not support priority to children in its current form. Since distinctions based on age ought to be positively justified, the failure of all these attempts at justification implies that the priority to children is ethically mistaken. Finally, the paper points to evidence that the paediatric priority reduces the overall supply of kidneys, at least in the United States. Paediatric priority is a real-world policy that seems discriminatory, in some places probably reduces the supply of organs, has no robust official defence, and is unsupported by mainstream ethical principles. Consequently, it should be ended. PMID- 27392663 TI - From the Editor-in-Chief. PMID- 27392664 TI - Problems/Solutions. PMID- 27392662 TI - Etiopathological mechanisms and clinical characteristics of hyperhemolysis syndrome in Spanish patients with thalassemia. AB - Hyperhemolysis syndrome (HHS) is characterized by severe intravascular hemolysis with a decrease in the reticulocyte count, which is triggered and aggravated by transfusion and cannot be explained by standard immunohematological studies. A nationwide study was conducted in order to retrospectively identify thalassemia patients with HHS in Spain in order to assess pre-disposing mechanisms for this syndrome. For this, the expression of adhesion (CD49, CD36) and complement related molecules (C3a, CD59) and the levels of reticulocyte apoptosis and macrophage activation were measured in 4 thalassemia patients with HHS, 14 patients without HHS, and 10 healthy subjects. Five of the six thalassemia patients had deltabeta-thalassemia. The patients were not alloimmunized prior to the syndrome, which was developed after the first transfusion in all but one case. Patients with deltabeta-thalassemia did not respond to corticoids or immunoglobulins; only splenectomy was successful. The expression of CD49 (alpha4beta1 integrin) was far higher in patients who had experienced HHS (85.07 +/- 18.46 vs. 46.28 +/- 24.31; p < 0.01), and the difference remained significant after correcting by the number of molecules analyzed (Bonferroni p < 0.05). In our population, deltabeta-thalassemia was the most common hemoglobinopathy in patients with HHS. Furthermore, the risk to develop this syndrome may be associated with an increased expression of alpha4beta1 integrin. PMID- 27392666 TI - What's Happening in Medicine! PMID- 27392665 TI - Washington Report on Health. PMID- 27392672 TI - [Not Available]. AB - OBJECTIVE: Tramadol is a weak opioid used as a step 2 analgesic, approved in France for moderate to severe pain. After dextropropoxyphene withdrawal, a national pharmacovigilance follow-up of tramadol was decided by the French Drug Agency. METHODS: All Serious Adverse Drug Reactions (SADR) notified with tramadol to the French PharmacoVigilance Centres (CRPV) and pharmaceutical companies between August 1(st), 2010 and July 31(th), 2011 were analyzed. RESULTS: During the study period, 296 cases of SADR were notified to CRPV and 59 to pharmaceutical companies. Apart from opiate-related SADR, tramadol induced serotoninergic SADR, including seizures or serotoninergic syndromes. Several " unlabelled " SADR were also identified: some of them, like hyponatremia or hypoglycemia, are poorly known by health professionals. Other were never published: peripheral edema or pancreatitis. CONCLUSION: This study shows that besides well-known opioid or serotoninergic ADR, tramadol can also induce 2 other relatively unknown ADR: hypoglycemia and hyponatremia. PMID- 27392671 TI - Intranasal Delivery of Umbilical Cord-Derived Mesenchymal Stem Cells Preserves Myelination in Perinatal Brain Damage. AB - Preterm white matter injury (WMI) is an important cause for long-term disability. Stem cell transplantation has been proposed as a novel therapeutic approach. However, intracerebral transplantation is not feasible for clinical purpose in newborns. Intranasal delivery of cells to the brain might be a promising, noninvasive therapeutic approach to restore the damaged brain. Therefore, our goal is to study the remyelinating potential of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) after intranasal delivery. Wistar rat pups, previously brain-damaged by a combined hypoxic-ischemic and inflammatory insult, received hWJ-MSC (150,000 cells in 3 MUL) that were intranasally delivered twice to each nostril (600,000 cells total). WMI was assessed by immunohistochemistry and western blot for myelination, astrogliosis, and microgliosis. The expression of preoligodendrocyte markers, and neurotrophic factors, was analyzed by real-time polymerase chain reaction. Animals treated with intranasally delivered hWJ-MSC showed increased myelination and decreased gliosis compared to untreated animals. hWJ-MSC may, therefore, modulate the activation of microglia and astrocytes, resulting in a change of the brain microenvironment, which facilitates the maturation of oligodendrocyte lineage cells. This is the first study to show that intranasal delivery of hWJ-MSC in rats prevented hypomyelination and microgliosis in a model of WMI in the premature rat brain. Further studies should address the dose and frequency of administration. PMID- 27392673 TI - [Not Available]. AB - Pholcodine is an opioid that has been widely used worldwide since 1950 for the treatment of non-productive cough in children and adults. The results of early preclinical studies but also those of recent clinical trials have shown the antitussive efficacy of pholcodine to be superior to that of codeine, of longer duration, and with an equivalent or safer toxicity profile. Also, there is no risk of addiction. Concern had been raised over a possible cross-sensitisation with neuromuscular blocking agents. While a recent assessment of the available data by the European Medicines Agency (EMA) has confirmed the favourable risk benefit ratio of pholcodine, further studies are needed to clear this point. PMID- 27392674 TI - Deriving Osteogenic Cells from Induced Pluripotent Stem Cells for Bone Tissue Engineering. AB - Induced pluripotent stem cells (iPSCs), reprogrammed from adult somatic cells using defined transcription factors, are regarded as a promising cell source for tissue engineering. For the purpose of bone tissue regeneration, efficient in vitro differentiation of iPSCs into downstream cells, such as mesenchymal stem cells (MSCs), osteoblasts, or osteocyte-like cells, before use is necessary to limit undesired tumorogenesis associated with the pluripotency of iPSCs. Until recently numerous techniques on the production of iPSC-derived osteogenic progenitors have been introduced. We reviewed these protocols and provided a perspective on the comparisons of osteogenic potentials of (1) iPSC-derived osteogenic cells produced by different protocols, (2) iPSCs from different somatic origins, and (3) iPSC-derived MSC-like cells and bone marrow stem cells. Finally, we discussed the potential application of the diseased iPSCs for systematic bone disorders. PMID- 27392670 TI - The Proteasome and Oxidative Stress in Alzheimer's Disease. AB - SIGNIFICANCE: Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is currently no effective Alzheimer's treatment and this, coupled with a growing aging population, highlights the necessity to understand the mechanism(s) of disease initiation and propagation. A major hallmark of Alzheimer's disease pathology is the accumulation of amyloid-beta (Abeta) aggregates (an early marker of Alzheimer's disease), and neurofibrillary tangles, comprising the hyper-phosphorylated microtubule-associated protein Tau. Recent Advances: Protein oxidation is frequently invoked as a potential factor in the progression of Alzheimer's disease; however, whether it is a cause or a consequence of the pathology is still being debated. The Proteasome complex is a major regulator of intracellular protein quality control and an essential proteolytic enzyme for the processing of both Abeta and Tau. Recent studies have indicated that both protein oxidation and excessive phosphorylation may limit Proteasomal processing of Abeta and Tau in Alzheimer's disease. CRITICAL ISSUES: Thus, the Proteasome may be a key factor in understanding the development of Alzheimer's disease pathology; however, its significance is still very much under investigation. FUTURE DIRECTIONS: Discovering how the proteasome is affected, regulated, or dysregulated in Alzheimer's disease could be a valuable tool in the efforts to understand and, ultimately, eradicate the disease. Antioxid. Redox Signal. 25, 886-901. PMID- 27392675 TI - Embracing Complex Associations in Common Traits: Critical Considerations for Precision Medicine. AB - Genome-wide association studies (GWAS) have identified numerous loci associated with human phenotypes. This approach, however, does not consider the richly diverse and complex environment with which humans interact throughout the life course, nor does it allow for interrelationships between genetic loci and across traits. As we move toward making precision medicine a reality, whereby we make predictions about disease risk based on genomic profiles, we need to identify improved predictive models of the relationship between genome and phenome. Methods that embrace pleiotropy (the effect of one locus on more than one trait), and gene-environment (G*E) and gene-gene (G*G) interactions, will further unveil the impact of alterations in biological pathways and identify genes that are only involved with disease in the context of the environment. This valuable information can be used to assess personal risk and choose the most appropriate medical interventions based on the genotype and environment of an individual, the whole premise of precision medicine. PMID- 27392676 TI - A cross-sectional study of psychological distress, burnout, and the associated risk factors in hospital pharmacists in Japan. AB - BACKGROUND: Opportunities for face-to-face communication with patients is increasing in modern hospital pharmacist practice. This may impose new burdens on hospital pharmacists. We performed a cross-sectional study to examine the prevalence of psychological distress, burnout, and compassion fatigue among hospital pharmacists. We also investigated possible relevant factors, such as sex, years of experience, hospital size, interpersonal work hours, and personality traits related to communication. METHODS: We mailed self-administered questionnaires to all pharmacists (n = 823) belonging to the prefectural society of hospital pharmacists in Japan. The questionnaires were the General Health Questionnaire (GHQ-12), Burnout (BO) and Compassion Fatigue and Secondary Traumatic Stress (CF/STS) subscales of the Professional Quality of Life Scale, the Autism Spectrum Quotient (AQ), and the Adult ADHD (attention deficit hyperactivity disorder) Self-Report Scale (ASRS). We examined associations between personality traits (AQ, ASRS) and psychological burden (GHQ-12, BO, CF/STS) using rank ANCOVA or multivariate logistic regression analyses. RESULTS: Complete responses were obtained from 380 pharmacists (46.2 % response rate). A substantial number of participants obtained scores that were higher than the cutoff points of the GHQ-12 (54.7 %), BO (49.2 %), and CF/STS (29.2 %). The GHQ 12 scores were negatively affected by years of experience (p < 0.001), and positively affected by AQ (p < 0.001) and ASRS (p < 0.001) scores. The BO scores was positively affected by AQ (p < 0.001) and ASRS (p = 0.001) scores, while the CF/STS (p = 0.023) score was negatively affected by years of experience, and positively affected by AQ (p < 0.001) and ASRS (p < 0.001) scores. CONCLUSIONS: There is a high prevalence of psychological distress and work-related burnout/CF among hospital pharmacists. Additionally, two common personality traits, such as autistic-like traits and ADHD-like symptoms, which might be related to communication style, could increase the risk of psychological distress and burnout/CF. Early risk assessment and preventive interventions that are specialized for these characteristics could protect individuals with these specific traits from burnout. PMID- 27392679 TI - Hinokitiol Production in a Suspension Culture of Calocedrus formosana Florin. AB - A suspension culture of Calocedrus formosana Florin was studied as a material for efficient production of hinokitiol. Murashige-Skoog's medium containing 3% sucrose and 1 mg/l 1-naphthylacetic acid was most desirable for cell growth. Cell growth, expressed as fresh cell weight, showed a 20-fold increase after 4 weeks of culture in this medium. Adding potassium acetate or chitosan to the medium increased hinokitiol production. The highest hinokitiol yield, 1700 MUg/g fresh cells, was obtained when cells were cultured in the growth medium with chitosan. PMID- 27392680 TI - Pheophorbide a Content and Chlorophyllase Activity in Green Tea. AB - We investigated the total content of pheophorbide a (PB a), which is sum of the contents of newly produced PB a, including PB a initially present and that converted from chlorophyllide a (Chd a) by the chlorophyllase reaction during incubation, in green tea samples, and found that the total content of PB a markedly increased in both Sencha and Matcha, compared with the initially present PB a content in each. This result demonstrates that chlorophyllase activity still remains in green tea, even after processing fresh green leaves. A comparison of the total contents of PB a produced during the incubation of chlorophyll a (Chl a) with Sencha and fresh green leaf acetone powder indicates that the ratio of chlorophyllase activity in Sencha and in fresh green leaves was about 1:20. PMID- 27392677 TI - Clinical and biomechanical researches of polyetheretherketone (PEEK) rods for semi-rigid lumbar fusion: a systematic review. AB - Lumbar spinal fusion using rigid rods is a common surgical technique. However, adjacent segment disease and other adverse effects can occur. Dynamic stabilization devices preserve physiologic motion and reduce painful stress but have a high rate of construct failure and reoperation. Polyetheretherketone (PEEK) rods for semi-rigid fusions have a similar stiffness and adequate stabilization power compared with titanium rods, but with improved load sharing and reduced mechanical failure. The purpose of this paper is to review and evaluate the clinical and biomechanical performance of PEEK rods. A systematic review of clinical and biomechanical studies was conducted. A literature search using the PubMed, EMBASE, and Cochrane Library databases identified studies that met the eligibility criteria. Eight clinical studies and 15 biomechanical studies were included in this systematic review. The visual analog scale and the Oswestry disability index improved significantly in most studies, with satisfactory fusion rates. The occurrence of adjacent segment disease was low. In biomechanical studies, PEEK rods demonstrated a superior load-sharing distribution, a larger adjacent segment range of motion, and reduced stress at the rod-screw/screw-bone interfaces compared with titanium rods. The PEEK rod construct was simple to assemble and had a reliable in vivo performance compared with dynamic devices. The quality of clinical studies was low with confounding results, although results from mechanical studies were encouraging. There is no evidence strong enough to confirm better outcomes with PEEK rods than titanium rods. More studies with better protocols, a larger sample size, and a longer follow-up time are needed. PMID- 27392678 TI - The impact of cerebral metastases growth pattern on neurosurgical treatment. AB - The surgical resection of cerebral metastases is one key element in a multimodal therapy of brain oligometastatic patients. Standard surgery alone is often not sufficient to achieve local control. Various reasons have been discussed including microscopic and macroscopic tumor rests after surgery and different growth patterns of cerebral metastases: In this review, we assessed the surgical standard technique and then analyzed the growth pattern of cerebral metastases and discussed its oncologic impact and new strategies in the surgical management of cerebral metastases. A major percentage of cerebral metastases are not sharply delimitated but show an irregular tumor-brain interface or even an infiltrative growth pattern. Different patterns of adjacent brain invasions have been described and may correlate with the prognosis of patients with cerebral metastasis. Even metastases of the same histological subtype and the same origin show a heterogeneous brain invasion pattern. Future therapeutic strategies might have to take this heterogeneity into account. An infiltrative growth pattern of cerebral metastases might be one reason for their extraordinary high local recurrence rate and might have an influence on the individual overall survival. An intraoperative detection of residual tumor and development of more radical surgical techniques is therefore an important neurooncological challenge and might result in better tumor control. Supramarginal resection of cerebral metastases is a promising approach. PMID- 27392681 TI - Isolation and Characterization of a Hydrogen Sulfide-Removing Bacterium, Pseudomonas sp. Strain DO-1. AB - Five microbial strains that removed hydrogen sulfide (H2S) or methylmercaptan (CH3SH) gas were newly isolated from soil samples. Strain DO-1, one of the isolates, was identified as a member of Pseudomonas sp., and it's immobilized cells removed 1 or 10 ppm of H2S gas within 2 hours. When strain DO-1 was cultured aerobically in a flask containing nutrient broth medium, the deodorizing activity increased, depending on the growth of the culture, and the maximum activity was obtained after 48 hours. Even though the immobilized cells were stored at 4 or 25 degrees C in sealed bottles for 6 months, the deodorizing activity remained. Throughout this study, strain DO-1 removed H2 S gas without preliminary feeding or exposure to sulfur com-pounds as growth substrates or inducers. These characteristics are advantageous for the deodorization of the malodorous gases surrounding us in daily life. PMID- 27392682 TI - Synthesis and Antifungal Activities of Furoxan Derivatives Designed as Novel Fungicide. AB - Furoxan derivatives 3-11 were designed and synthesized as potential fungicides. Symmetrically substituted furoxan derivatives 3a-j were prepared by dimerization of the corresponding nitrile oxide generated from N-hydroxyliminoyl chloride 2 in situ. Further functional group modifications of aldehyde 4, a key intermediate, generated furoxan derivatives 5-11. The fungicidal activities of furoxan derivatives 3-11 were observed over a broad spectrum of plant fungi at 250 ppm. PMID- 27392683 TI - Relationship between Suspension Properties and Fibril Structure of Disintegrated Bacterial Cellulose. AB - A new method evaluating the fibril width and length of disintegrated bacterial cellulose was developed using optical and rheological analysis. During the early stages of the disintegration process, the bacterial cellulose particles formed loose fibrous aggregates, followed by cutting of the disintegrated fibrils that produced short fibrils. On the other hand, the fibril width decreased steadily throughout disintegration. The relationships between fibril structure and suspension properties were analyzed by a multiple regression method. The thinner and longer the disintegrated bacterial cellulose fibrils were, the higher the viscosity and water-holding capacity became. PMID- 27392684 TI - Stereoselective Synthesis of (2R, 3S)-2-Benzyl-2-hydroxy-3- (3,4 methylenedioxybenzyl)-gamma-butyrolactone from L-(+)-Arabinose. AB - As a model experiment for the stereoselective synthesis of optically active cis alpha,beta-dibenzyl-alpha-hydroxy-gamma-butyrolactone, (2R, 3S)-2-benzyl-2 hydroxy-3-(3,4-methylenedioxybenzyl)-gamma-butyrolactone (3) was stereoselectively synthesized from L-(+)-arabinose. PMID- 27392685 TI - Evaluation of the Cytotoxic Activity of Chiral (E)-13-Hydroxy-10-oxo-11 octadecenoic Acid and Its Lactone. AB - Both the S and R enantiomers of (E)-13-hydroxy-10-oxo-11-octadecenoic acid (1) and (E)-10-oxo-11-octadecen-13-olide (2) had similar IC50 values against P388 mouse leukemia cells; i.e. the stereochemistry of the asymmetric center of 1 and 2 had no influence on the cytotoxic activity. Bioassay results of various compounds related to 1 and 2 suggests that the 10-oxo and lactone moieties of 2 were important for enhancing the cytotoxicity. PMID- 27392686 TI - Increased Cellulose Production from Sucrose by Acetobacter after Introducing the Sucrose Phosphorylase Gene. AB - A sucrose phosphorylase (SPase) gene derived from Leuconostoc mesenteroides was introduced into a cellulose-producing Acetobacter strain and expressed under the lac promoter. The activity of the SPase was detected in extracts of the transformed cells and cellulose production from sucrose by the cells was found to have increased, which strongly suggests that the increase was the result of the new metabolizing pathway. Furthermore, the level of SPase expression was increased by altering the length of the lac promoter. PMID- 27392687 TI - secA341 Mutation Inhibition of Expression of the Bacillus subtilis Protease Gene, aprE. AB - The production of extracellular protease(s) of Bacillus subtilis is induced in the post-exponential growth phase, and is severely reduced in a strain carrying a temperature sensitive mutation (secA341(ts)) in the secA gene, the product of which is required for protein secretion. The expression of the extracellular serine protease gene, aprE, as monitored by the beta-galactosidase activity of an aprE-lacZ translational fusion, was inhibited in the secA341 mutant cell and restored by the introduction of the degU32(Hy) mutation, which makes the phosphorylated DegU response regulator of a two-component system refractory to dephosphorylation and causes the cell to become a strong producer of AprE. The secA341 mutation appears to block some activation step required for aprE expression. PMID- 27392688 TI - Facile Syntheses of AM-toxins and Analogs as Cyclic Depsipeptides by the Solid phase Method. AB - The cyclic depsipeptides, AM-toxins I and II and AM-toxin I analogs, were efficiently and rapidly prepared by the Fmoc-based solid-phase method for the synthesis of linear depsipeptides, with N-[(dimethylamino)-1H-1,2,3-triazolo[4,5 b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) being used for their subsequent cyclization. PMID- 27392689 TI - Stability of Thermostable Enzyme, Aqualysin I ; a Subtilisin-type Serine Protease from Thermus aquaticus YT-1. AB - We characterized the heat stability and detergent stabilities of aqualysin I, produced by Thermus aquaticus YT-1, and compared them with those of fungal proteinase K and Bacillus subtilisin. Aqualysin I displayed excellent heat and detergent stabilities. Proteinase K, another Cys-containing enzyme, was less stable than aqualysin I. All these enzymes maintained activities in the presence of urea or Tween-20. PMID- 27392690 TI - Detection of Proteins Binding to the Promoter Region DNA Using a Nonradioactive Gel-Retardation Assay. AB - Binding of nuclear proteins to the promoter region was studied by a nonradioactive gel-retardation assay. The procedure uses biotinylated oligonucleotides in combination with streptavidin and biotin-conjugated alkaline phosphatase. This method offers sensitivity comparable to radioactive detection, and the advantage of the high stability of probes. Moreover the hazards of usage associated with radiation are avoided. PMID- 27392691 TI - Structural Confirmation of Cotylenin A, a Novel Fusicoccane-diterpene Glycoside with Potent Plant Growth-regulating Activity from Cladosporium Fungus sp. 501-7W. AB - The structure of cotylenin A, a potent plant-growth stimulant with the most complex molecule in cotylenins from Cladosporium fungus sp. 501-7W, was analyzed again by HMBC experiments and X-ray crystallography of its diacetyl dihydroderivative. The previously proposed stereostructure of cotylenin A was thus completely confirmed. PMID- 27392692 TI - Study on the Application of the (S)-2-tert-Butyl-2-methyl-1,3-benzodioxole-4 carboxylic acid-based On-line HPLC-Exciton CD Analysis to Acyclic 1,3-Diols. AB - The application of the on-line HPLC-exciton CD analysis with (S)-TBMB-carboxylic acid that simultaneously determined the enantiomeric composition and absolute configuration of vicinal diols, diamines and amino alcohols to 1,3-diols was studied. All optical isomers of di-O-(S)-TBMB-carbonyl-1,3-butanediols and 2,4 pentanediols were separated and their absolute configurations were determined without reference samples on line by HPLC. PMID- 27392693 TI - Identification and Characterization of Acinetobacter sp. CNU961 Able to Grow with Phenol at High Concentrations. AB - An Acinetobacter sp., strain CNU961, with a higher tolerance to phenol was isolated, and identified through a set of taxonomic studies and a genetic complementation test. Enzymatic and mutagenic studies found that the strain dissimilate phenol by hydroxylation to catechol followed by an ortho-ring cleavage pathway to further mineralize it. The phenol hydroxylase, which is an inducible enzyme and requires NADPH for optimum activity, was not inhibited by phenol at concentrations up to 0.5 mM. The different kinetic behaviors of the enzyme activities on NADPH and on phenol reflected that the phenol hydroxylase of strain CNU961 is a multisubunit allosteric enzyme consisting of heterogeneous polypeptides. PMID- 27392695 TI - Overexpression of membrane-bound gluconate-2-dehydrogenase to enhance the production of 2-keto-D-gluconic acid by Gluconobacter oxydans. AB - BACKGROUND: 2-keto-D-gluconic acid (2KGA) is widely used as a chemical intermediate in the cosmetic, pharmaceutical and environmental industries. Several microbial fermentation processes have been developed for production of 2KGA but these suffer from substrate/product inhibition, byproduct formation and low productivity. In previous work, we showed that 2KGA can be specifically produced from glucose (Glu) or gluconic acid (GA) by resting wild-type Gluconobacter oxydans DSM2003 cells, although substrate concentration was relatively low. In this study, we attempted to improve 2KGA productivity by G. oxydans DSM2003 by overexpressing the ga2dh gene, which encodes the membrane bound gluconate-2-dehydrogenase enzyme (GA2DH). RESULTS: The ga2dh gene was overexpressed in G. oxydans DSM2003 under the control of three promoters, P tufB , P ga2dh or P ghp0169 , respectively. Among the recombinant strains obtained, G. oxydans_tufB_ga2dh showed a similar growth rate to that of the control strain and displayed the highest specific productivity of 2KGA from GA, which was increased nearly twofold compared with that of the control strain during batch biotransformation. When biocatalysis conditions were optimized, with provision of sufficient oxygen during biotransformation, up to 480 g/L GA was completely utilized over 45 h by resting cells of G. oxydans_tufB_ga2dh and 453.3 g/L 2KGA was produced. A productivity of 10.07 g/L/h and a yield of 95.3 % were obtained. Overexpression of the ga2dh gene also significantly improved the conversion of Glu to 2KGA. Under optimized conditions, 270 g/L Glu was converted to 321 g/L 2KGA over 18 h, with a yield of 99.1 % and a productivity of 17.83 g/L/h. The glucose concentrations during the batch biotransformation and the 2KGA productivities achieved in this study were relatively high compared with the results of previous studies. CONCLUSIONS: This study developed an efficient bacterial strain (G. oxydans_tufB_ga2dh) for the production of 2KGA by overexpressing the ga2dh gene in G. oxydans. Supply of sufficient oxygen enhanced the positive effect of gene overexpression on 2KGA production. Gluconobacter oxydans_tufB_ga2dh is thus a competitive species for use in 2KGA production. PMID- 27392694 TI - Q&A: How does peptide signaling direct plant development? AB - A significant part of the communication between plant cells is mediated by signaling peptides and their corresponding plasma membrane-localized receptor like kinases. This communication mechanism serves as a key regulatory unit for coordination of plant growth and development. In the past years more peptide receptor signaling pathways have been shown to regulate developmental processes, such as shoot and root meristem maintenance, seed formation, and floral abscission. More detailed understanding of the processes behind this regulation might also be helpful to increase the yield of crop plants. PMID- 27392696 TI - CropWatch agroclimatic indicators (CWAIs) for weather impact assessment on global agriculture. AB - CropWatch agroclimatic indicators (CWAIs) are a monitoring tool developed by the CropWatch global crop monitoring system in the Chinese Academy of Sciences (CAS; www.cropwatch.com.cn , Wu et al Int J Digital Earth 7(2):113-137, 2014, Wu et al Remote Sens 7:3907-3933, 2015). Contrary to most other environmental and agroclimatic indicators, they are "agronomic value-added", i.e. they are spatial values averaged over agricultural areas only and they include a weighting that enhances the contribution of the areas with the largest production potential. CWAIs can be computed for any time interval (starting from dekads) and yield one synthetic value per variable over a specific area and time interval, for instance a national annual value. Therefore, they are very compatible with socio-economic and other variables that are usually reported at regular time intervals over administrative units, such as national environmental or agricultural statistics. Two of the CWAIs are satellite-based (RAIN and Photosynthetically Active radiation, PAR) while the third is ground based (TEMP, air temperature); capitals are used when specifically referring to CWAIs rather than the climate variables in general. The paper first provides an overview of some common agroclimatic indicators, describing their procedural, systemic and normative features in subsequent sections, following the terminology of Binder et al Environ Impact Assess Rev 30:71-81 (2010). The discussion focuses on the systemic and normative aspects: the CWAIs are assessed in terms of their coherent description of the agroclimatic crop environment, at different spatial scales (systemic). The final section shows that the CWAIs retain key statistical properties of the underlying climate variables and that they can be compared to a reference value and used as monitoring and early warning variables (normative). PMID- 27392697 TI - Overview of the ISRTP October 2014 workshop on GRAS determinations. AB - On October 12-13, 2014 the ISRTP held a very successful Workshop on GRAS Determinations in Washington DC that was not only well-attended by seasoned public and private professionals from a wide swath of food safety disciplines but featured a series of very insightful and informative presentations from current and past officials from the US Food & Drug Administration (FDA). To stay true to our international nature as a Society, we had regulatory and industry representatives from Canada and Europe. PMID- 27392698 TI - Alternative to antibiotics against Pseudomonas aeruginosa: Effects of Glycyrrhiza glabra on membrane permeability and inhibition of efflux activity and biofilm formation in Pseudomonas aeruginosa and its in vitro time-kill activity. AB - The multi-drug resistance offered by Pseudomonas aeruginosa to antibiotics can be attributed towards its propensity to develop biofilm, modification in cell membrane and to efflux antibacterial drugs. The present study explored the activity of Glycyrrhiza glabra and one of its pure compounds, glycyrrhizic acid against P. aeruginosa and their mechanism of action in terms of the effect on membrane permeability, efflux activity, and biofilm formation were determined. Minimum inhibitory concentrations were determined by using broth dilution technique. The minimum bactericidal concentrations were assessed on agar plate. The MIC of the extract and glycyrrhizic acid was found to be 200 and 100 MUg ml( 1), respectively. The MBC was found to be 800 and 400 MUg ml(-1) in the case of extract and glycyrrhizic acid, respectively. Time -dependent killing efficacy was also estimated. Flowcytometric analysis with staining methods was used to determine the effect of extract and glycyrrhizic acid at 2 * MIC on different physiological parameters and compared it with the standard (antibiotic). The growth of P. aeruginosa was significantly inhibited by extract and the pure compound. The herbal extract and the glycyrrhic acid were also found to effective in targeting the physiological parameters of the bacteria that involve cell membrane permeabilization, efflux activity, and biofilm formation. This study reports the antipseudomonal action of Glycyrrhiza glabra and one of its compound and provides insight into their mode of action. PMID- 27392699 TI - Molecular characterization of Staphylococcus aureus isolates from southwest of Iran using spa and SCCmec typing methods. AB - Staphylococcus aureus remains a major cause of nosocomial infection worldwide. Characterization of S. aureus isolates circulating in the southwest of Iran will contribute to understand and control the spread of the strains in this area. spa and SCCmec typing methods were used for genotyping of 125 S. aureus isolates obtained from two teaching hospitals in Ahvaz. Drug susceptibility testing was performed by using disk diffusion method. Frequency of the methicillin resistant S. aureus (MRSA) isolates was 39% (n = 34) and 27% (n = 10) in Emam Khomeini and Golestan hospitals, respectively. Except for Erythromycin, MRSA strains showed high rate of resistance to antimicrobial agents including penicillin (100%), norfloxacine (80%), azitromycin (80%), ciprofloxacin (80%), gentamycin (77%), cotrimoxazole (75%), cephotaxime. All isolates were sensitive to vancomycin. Out of 44 MRSA strains, 39 (88.5%) were SCCmec III, three (7%) were IVc and two (4.5%) of them were nontypeable. spa types t037 (26 isolates; 59%), and t1149 (25 isolates; 31%) were the most dominant types found in MRSA and methicillin sensitive S. aureus (MSSA) strains, respectively. We found SCCmec type III as the most prominent type indicating that most of the studied bacterial population had hospital origin. spa type t037, the most frequent genotype in this study were significantly (100%) associated with MRSA. For the first time we are reporting spa types t692, t706 and t018 from Iran and t342, t704, t2622, t5598, t11270 and t2864 from Asia. Moreover we are reporting types t6871 and t2684 for the second time in the world. PMID- 27392700 TI - In vivo bactericidal effect of Melaleuca alternifolia essential oil against Aeromonas hydrophila: Silver catfish (Rhamdia quelen) as an experimental model. AB - Aeromonas hydrophila is one of the main causative agent of high mortality and significative economic losses in aquaculture and has become increasingly resistant to conventional antibiotics. One feasible alternative to control and treat it is the use of essential oils. This study aimed to evaluate A. hydrophila susceptibility to tea tree oil (TTO-Melaleuca alternifolia) in vivo, and the effect of this treatment. In vivo tests were performed using silver catfish (Rhamdia quelen) as the experimental model. Silver catfish were treated with TTO at 25 and 50 MUL/L for seven days before infection. After seven days, the fish were inoculated with A. hydrophila via intramuscularly. Treatment with TTO at 50 MUL/L was able to extend longevity of infected fish, and showed 88% of therapeutic success, even though it did not show curative efficacy. TTO treatment was not toxic under these tested concentrations, since biomarkers of hepatic and renal functions were not affected, and the concentration of 50 MUL/L was able to prevent increased levels of aspartate aminotransferase. There was no significative differences regarding hematological parameters (p < 0.05). Treatment with TTO 50 MUL/L was able to reduce histopathological alterations usually caused by this type of bacteria in the gills, but it was unable to reduce hepatic histopathological alterations. Our results showed, for the first time, that TTO has high activity against A. hydrophila and proved to be a natural alternative to prevent and control this pathogen. PMID- 27392701 TI - Mechanistic insights into the mode of action of anticandidal sesamol. AB - Previously we have deciphered the antifungal effect of sesamol (Ses), a phenolic compound obtained from sesame oil, against human fungal pathogen Candida albicans. To gain deeper insights into the possible mechanisms involved, transcription profiling was done in presence of Ses which revealed various targets through which Ses was barricading the growth of C. albicans. We observed that Ses perturbs membrane integrity confirming our previous observations and displayed disrupted plasma membrane ATPase activity. We further investigated that Ses leads to inhibited morphological transition, biofilm formation and epithelial cell adhesion which are significant virulence attributes required for pathogenesis. Interestingly, Ses also causes amendment in iron homeostasis as revealed by hypersensitivity under iron deprivation, ferroxidase assay to estimate iron levels and concomitant upregulation of FTR2, a high affinity iron transporter. Finally we assessed that Ses causes defect in mitochondrial functioning and DNA repair mechanism. Together, being source of consumable natural product, further studies on Ses are warranted so that it can be exploited as effective antifungal agent. PMID- 27392702 TI - ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. PMID- 27392703 TI - Professionalism in Cardiac Imaging : The Mario S. Verani MD Lecture. PMID- 27392704 TI - Prenatal Stress and the Cortisol Awakening Response in African-American and Caucasian Women in the Third Trimester of Pregnancy. AB - Objectives Prior studies have shown significant racial disparities in psychosocial stressors for pregnant women. One physiological mechanism by which prenatal stress is expressed is via the stress-sensitive hormone cortisol, which itself differs by race. In this study, we examine differences in cortisol awakening response (CAR) for African-American and Caucasian pregnant women during late pregnancy, particularly whether racial disparities are evident after accounting for measures of psychosocial stress. Methods During their third trimester of pregnancy (32-40 weeks of gestation), we asked women to self-collect salivary samples at home over 2 days. We then measured salivary cortisol across the day for 30 pregnant women (18 Caucasian; 12 African-American) to examine the CAR by race and by multiple measures of self-reported psychosocial stress, including perceived discrimination. Results Although the women in our sample showed normative cortisol diurnal rhythms (high on waking, peak 30 min post waking, lowest at bedtime), we found that African-American women had blunted (smaller) awakening responses compared to Caucasian women (p < 0.05). The CAR was significantly larger in Caucasian women compared to African-American women even after accounting for covariates in a multivariate equation. However, when we added measures of psychosocial stress to the multivariate equation, higher levels of stress were significantly associated with a smaller CAR (p < 0.05), and the association between maternal race and CAR was no longer significant. Conclusions Our results add to a growing body of evidence that racial differences in the activity of the hypothalamic-pituitary-adrenal axis are associated with psychosocial stress during pregnancy. PMID- 27392705 TI - Guidelines and Interventions Related to the Postpartum Visit for Low-Risk Postpartum Women in High and Upper Middle Income Countries. AB - Objectives A two-part review was undertaken to: (1) summarize current guidelines on the timing and frequency of postpartum follow-up care for generally healthy, non-high risk postpartum women and to delineate the evidence on which these guidelines are based; and, (2) summarize the results of intervention studies focused on increasing utilization of the postpartum visit for generally healthy, non-high risk postpartum women. Methods A review of guidelines from high and upper middle income countries published between 2000 and 2016 in English related to non-high risk postpartum follow-up visits was conducted in 2014-2016 using four databases and additional sources. In addition, articles published between 1990 and 2016 which evaluated interventions from high to upper middle income countries related to increasing attendance at the postpartum visit were gathered using three databases. Results This review located eight guidelines, all of which relied on expert opinion/group consensus as the evidence for their recommendations regarding the timing of the postpartum visit. The review located 19 intervention studies focused on increasing use of the postpartum visit; in 12 there was statistically significant evidence that these approaches improved utilization. However, no intervention strategy was evaluated more than a few times and many of the evaluations were relatively dated. Conclusions Guidelines for the timing of the postpartum visit are variable and are typically based on weak evidence; however, there is support for increased flexibility to meet women's needs. Additionally, while there is a diverse set of promising interventions to increase utilization of the postpartum visit, there is limited evaluative information. Future initiatives should focus on more rigorous evaluation. PMID- 27392706 TI - Maternal Pre-pregnancy BMI and Reproductive Health of Daughters in Young Adulthood. AB - Objective To investigate the possible associations between maternal pre-pregnancy body mass index (BMI) and daughters' age of menarche and subsequent markers of reproductive health. Methods Nine hundred eighty-five pregnant women (80 %) were enrolled at their routine 30th week examinations in 1988-1989. In 2008, a follow up questionnaire was completed for 365 daughters (83 %), while 267 daughters (61 %) participated in a subsequent clinical examination. Main outcome measures were age of menarche, reproductive hormone profile, and ovarian follicle count in daughters. Results Daughters of mothers in the highest pre-pregnancy BMI tertile (BMI >= 22.0 kg/m(2)) had an adjusted 4.1 (0.3; 8.0) months earlier menarche compared with the middle tertile group (BMI 20.0-21.9 kg/m(2)). Among non-users of hormonal contraceptives, daughters of mothers in the highest pre-pregnancy BMI tertile had non-significantly lower dehydroepiandrosterone-sulphate (DHEAS), estradiol, and free estrogen index (FEI), compared to the middle BMI tertile. This was supported by a sub-analysis using the WHO classification (underweight, BMI < 18.50; normal range, BMI 18.50-24.99; overweight/obese, BMI >= 25.00 kg/m(2)) as exposure groups, in which daughters of overweight mothers had lower levels of DHEAS and estradiol, and lower FEI compared to daughters of normal weight mothers. No associations were found for ovarian follicle count in any of the groups. Conclusions for Practice We found that higher maternal BMI is associated with earlier age of menarche in daughters. A possible impact of maternal pre-pregnancy BMI on DHEAS and estradiol serum levels, and FEI in non users of hormonal contraceptives was indicated, but the results were not statistically significant. PMID- 27392707 TI - [Not Available]. AB - Hyponatremia is a rare side effect described in the product characteristics of proton pump inhibitors (PPIs). Hyponatremia in the elderly (>65years) was assessed in patients with exposure to PPIs for at least one year compared to controls not exposed to PPIs counterparts. Included 145 patients, twenty-four patients (16.6%) had moderate hyponatremia ([120-134] mEq/L). Forty-eight patients (33.1%) were treated with PPIs. In the end, 31.3% [18.7%-46.3%] of the treated population for more than a year by PPI suffered moderate hyponatremia against only 9.3% [14.3%-16.9%] in the rest of the population, giving an odds ratio of 4.4 ([1.8-11.1], p=0.001). The relationship between hyponatremia dose was not significant (R(2)=0.05, p=0.74). By our study, we show that the risk of moderate hyponatremia is increased by chronic use of PPI in the elderly population. We also specify a notion of prevalence between 18.7% and 46.3%. PMID- 27392708 TI - [Not Available]. AB - To quantify and characterize the use of the Internet to search for information about medicines. METHODS: A random sample of subjects was interviewed in the city of Bordeaux (France) in November 2012 regarding their use of the Internet to find information on medicines. RESULTS: Among 103 interviewed subjects (median age: 38years; 53.4% of men), 48 (46.6%) reported using the Internet to find information about medicines (58.3% of women). Two-thirds (66.7%) declared visiting consumer forums. However, nearly 60% reported to first consult a health professional. Three subjects had already bought medicines on the web and half (52.0%) of those who never made a purchase on the Internet would not trust the quality of the medicine. CONCLUSION: Even if purchasing medicines on the web remains rare, this media is frequently used to find information on medicines and most often on websites of questionable quality. PMID- 27392709 TI - Lp-PLA2 silencing protects against ox-LDL-induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages. AB - Atherosclerosis is a disease of the large- and medium-size arteries that is characterized by the formation of atherosclerotic plaques, in which foam cells are the characteristic pathological cells. However, the key underlying pathomechanisms are still not fully elucidated. In this study, we investigated the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in ox-LDL-induced oxidative stress and cell apoptosis, and further, elucidated the potential machanisms in human THP1 macrophages. Flow cytometry and western blot analyses showed that both cell apoptosis and Lp-PLA2 expression were dose-dependently elevated after ox-LDL treatment for 24 h and also time-dependently increased after 50 mg/L ox-LDL incubation in THP1 macrophages. In addition, Lp-PLA2 silencing decreased ox-LDL-induced Lp-PLA2 and CD36 expression in THP1 macrophages. We also found that the levels of oil red O-staining, triglyceride (TG) and total cholesterol (TC) were significantly upregulated in ox-LDL-treated THP1 cells, but inhibited by Lp-PLA2 silencing. Furthermore, ox-LDL treatment resulted in significant increases of ROS and MDA but a marked decrease of SOD, effects that were reversed by Lp-PLA2 silencing in THP1 cells. Lp-PLA2 silencing reduced ox-LDL-induced cell apoptosis and caspase-3 expression in THP1 cells. Moreover, Lp-PLA2 siRNA transfection dramatically lowered the elevated levels of p-Akt and p-mTOR proteins in ox-LDL-treated THP1 cells. Both PI3K inhibitor LY294002 and mTOR inhibitor rapamycin decreased the augmented caspase-3 expression and TC content induced by ox-LDL, respectively. Taken together, these results revealed that Lp-PLA2 silencing protected against ox-LDL-induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages. PMID- 27392710 TI - Keeping Our Calcium in Balance to Maintain Our Balance. AB - Calcium is a key signaling molecule and ion involved in a variety of diverse processes in our central nervous system (CNS) which include gene expression, synaptic transmission and plasticity, neuronal excitability and cell maintenance. Proper control of calcium signaling is not only vital for neuronal physiology but also cell survival. Mutations in fundamental channels, transporters and second messenger proteins involved in orchestrating the balance of our calcium homeostasis can lead to severe neurodegenerative disorders, such as Spinocerebellar (SCA) and Episodic (EA) ataxias. Hereditary ataxias make up a remarkably diverse group of neurological disorders clinically characterized by gait ataxia, nystagmus, dysarthria, trunk and limb ataxia and often atrophy of the cerebellum. The largest family of hereditary ataxias is SCAs which consists of a growing family of 42 members. A relatively smaller family of 8 members compose the EAs. The gene mutations responsible for half of the EA members and over 35 of the SCA subtypes have been identified, and several have been found to be responsible for cerebellar atrophy, abnormal intracellular calcium levels, dysregulation of Purkinje cell pacemaking, altered cerebellar synaptic transmission and/or ataxia in mouse models. Although the genetic diversity and affected cellular pathways of hereditary ataxias are broad, one common theme amongst these genes is their effects on maintaining calcium balance in primarily the cerebellum. There is emerging evidence that the pathogenesis of hereditary ataxias may be caused by imbalances in intracellular calcium due to genetic mutations in calcium-mediating proteins. In this review we will discuss the current evidence supporting the role of deranged calcium as the culprit to neurodegenerative diseases with a primary focus on SCAs and EAs. PMID- 27392711 TI - Expression analysis of Egr-1 ortholog in metamorphic brain of honeybee (Apis mellifera L.): Possible evolutionary conservation of roles of Egr in eye development in vertebrates and insects. AB - Specific genes quickly transcribed after extracellular stimuli without de novo protein synthesis are known as immediate early genes (IEGs) and are thought to contribute to learning and memory processes in the mature nervous system of vertebrates. A recent study revealed that the homolog of Early growth response protein-1 (Egr-1), which is one of the best-characterized vertebrate IEGs, shared similar properties as a neural activity-dependent gene in the adult brain of insects. With regard to the roles of vertebrate Egr-1 in neural development, the contribution to the development and growth of visual systems has been reported. However, in insects, the expression dynamics of the Egr-1 homologous gene during neural development remains poorly understood. Our expression analysis demonstrated that AmEgr, a honeybee homolog of Egr-1, was transiently upregulated in the developing brain during the early to mid pupal stages. In situ hybridization and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry revealed that AmEgr was mainly expressed in post-mitotic cells in optic lobes, the primary visual center of the insect brain. These findings suggest the evolutionarily conserved role of Egr homologs in the development of visual systems in vertebrates and insects. PMID- 27392712 TI - E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response. AB - HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. PMID- 27392713 TI - Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation. AB - Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mphi) containing tumor necrosis factor-alpha (TNF-alpha). We found that sex hormones downregulated TNF-alpha-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-kappaB) sites, whereas non-canonical NF-kappaB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. PMID- 27392714 TI - Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells. AB - Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to "copper" cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. PMID- 27392716 TI - Comparative Assessment of Off-label and Unlicensed Drug Prescriptions in Children: FDA Versus ANSM Guidelines. AB - PURPOSE: The main objectives of this study were to assess the incidence of off label (OL) and/or unlicensed (UL) prescriptions in a sample of pediatric Lebanese patients by using US Food and Drug Administration (FDA) and the French Medical Regulatory Authority (ANSM) regulations. The goal was to analyze the divergences between regulations and to identify those drugs most commonly involved in OL-UL utilization. METHODS: This study was a retrospective analysis (500 pediatric files) conducted in a Lebanese University hospital in 3 pediatric wards (chronic diseases, acute diseases, and the pediatric intensive care unit). FINDINGS: The frequency of OL-UL drug use was significantly different between pediatric wards (P < 0.001), with the highest incidence occurring in the intensive care unit. The most frequent OL-UL prescriptions occurred with cancer (oncology) admissions. Age was significantly related to OL-UL frequency (highest incidence in children aged between 0 and 1 year). The number of drugs prescribed per patient ranged between 1 and 20 (mean [SD], 4.13 [2.6]). The incidence of OL-UL prescriptions was significantly higher in patients treated with a greater number of medicines (P < 0.001). Overall, 58.9% of drug prescriptions were authorized according to ANSM and 50.7% according to FDA regulations; 11.1% (ANSM) and 15.8% (FDA) were UL, and 30.2% (ANSM) and 33.5% (FDA), respectively, were OL use (where OL for the indication were the most common). The highest percentage of OL-UL prescriptions was seen with the following groups: blood and blood-forming organs, genitourinary system, and sex hormones. Divergence between FDA and ANSM was mainly observed for OL medicines. UL prescriptions assessed according to both regulations showed similar results. IMPLICATIONS: This study highlights the need for prescribers to continuously examine updates to official regulations to avoid using an OL-UL drug whenever possible. It also calls for better harmonization between worldwide official guidelines concerning drugs used in children to reduce risk factors for adverse drug reactions. PMID- 27392717 TI - Antimicrobial Stewardship Program Members' Perspectives on Program Goals and National Metrics. AB - PURPOSE: This study compares antimicrobial stewardship program (ASP)-stated goals and outcomes collected as well as opinions regarding national metric establishment. METHODS: Twenty-one ASP members underwent telephone interviews answering open-ended questions about ASP goals, outcomes collected, and opinions about national metrics. Content analysis was used to code responses into predefined ASP-metric categories. FINDINGS: The most common ASP goal was antimicrobial appropriateness (76%), outcomes tracked were use and microbial outcomes (both 71%), and desired national metric was use (67%). IMPLICATIONS: Stated-goals, outcomes tracked, and opinions regarding national metric establishment did not fully align. With ASP-related regulations looming, it is important that alignment is increased. PMID- 27392715 TI - Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction. AB - The aging process appears to be a precursor to many age-related diseases, perhaps the most impactful of which is cardiovascular disease (CVD). Heart disease, a manifestation of CVD, is the leading cause of death in the USA, and heart failure (HF), a syndrome that develops as a consequence of heart disease, now affects almost six million American. Importantly, as this is an age-related disease, this number is likely to grow along with the ever-increasing elderly population. Hallmarks of the aging process and HF patients with a reduced ejection fraction (HFrEF) include exercise intolerance, premature fatigue, and limited oxygen delivery and utilization, perhaps as a consequence of diminished peripheral vascular function. Free radicals and oxidative stress have been implicated in this peripheral vascular dysfunction, as a redox imbalance may directly impact the function of the vascular endothelium. This review aims to bring together studies that have examined the impact of oxidative stress on peripheral vascular function and oxygen delivery and utilization with both healthy aging and HFrEF. PMID- 27392718 TI - Reliability in the process of care during emergency general surgical admission: A prospective cohort study. AB - INTRODUCTION: Emergency general surgery (EGS) is responsible for 80-90% of surgical in-hospital deaths and the early management of these unwell patients is critical to improving outcomes. Unfortunately care for EGS patients is often fragmented and important care processes are frequently omitted. METHODS: This study aimed to define a group of important processes during EGS admission and assess their reliability. Literature review and semi-structured interviews were used to define a draft list of processes, which was refined and validated using the Delphi consensus methodology. A prospective cohort study of the 22 included processes was performed in 315 patients across 5 acute hospitals. RESULTS: Prospective study of the 22 selected processes demonstrated omission of 1130/5668 (19.9%) processes. Only 6 (1.9%) patients had all relevant processes performed correctly. Administration of oxygen to hypoxic patients (82/129, 64%), consultant review (202/313, 65%) and administration of antibiotics within 3 h for patients with severe sepsis (41/60, 68%) were performed particularly poorly. There were significant differences in the mean number of omissions per patient between hospitals ( ANOVA: F = 11.008, p < 0.001) and this was strongly correlated with hospitals' median length of stay (Spearman's rho = 0.975, p = 0.005). CONCLUSIONS: Reliability of admissions processes in this study was poor, with significant variability between hospitals. It is likely that improvements in process reliability would enhance EGS patients' outcomes. This will require engagement of the entire surgical team and the implementation of multiple interventions to improve the effectiveness of the admission phase of care. PMID- 27392719 TI - Using satellite imagery and GPS technology to create random sampling frames in high risk environments. AB - INTRODUCTION: Health surveys are important tools for assessing needs and informing policy decisions. However, obtaining representative samples is challenging in environments without traditional infrastructure or census data. We describe a method using satellite imagery, geographic information systems and GPS technology to obtain an accurate sample of such a population. METHODS: The Kerenik Camp in Darfur is a conflict-heavy environment with 25,000 internally displaced persons (IDPs). We requisitioned high-resolution satellite imagery of the camp prior to arrival. Structures identified as potential domiciles were geocoded with a unique ID and coordinate. A random selection of ID numbers formed the representative sample. Researchers visited these coordinates using handheld GPS devices and administered surveys to the inhabitants. RESULTS: 2219 geocoded points were visited. Of these, 1655 (74.6%) proved to be unique domiciles. Our survey participation rate was 87.1%. The overall effective rate of completed survey per geocoded point visited was 39.1%. DISCUSSION: Our sampling technique offers several advantages when surveying vulnerable populations. It permits the establishment of a sampling frame without need for traditional infrastructure, such as addresses or telephones. Sampling frames can be constructed remotely and prior to survey initiation, important considerations for insecure environments where time on the ground may be limited. CONCLUSION: This technique can be used for any setting requiring a random sample, but is especially useful in insecure environments and survey areas without accessible census data, postal addresses, or telephone numbers. Sampling frames can be constructed remotely and prior to survey initiation, important considerations for environments where time on the ground may be limited. PMID- 27392720 TI - Videofluoroscopy and oropharyngeal manometry for evaluation of swallowing in elderly patients. AB - Presbyphagia represents the physiological aging evolution of the swallowing function. It is related to the natural changes of the anatomical structures involved in the swallowing process. These age-related modifications can be asymptomatic in the early stages of life, but in the late stages, they could lead to dysphagia, aspiration pneumonia, dehydration, or malnutrition, reducing the quality of life. Videofluoromanometry (VFM) is the combined study of videofluoroscopy (VFS) and oropharyngeal manometry that allows simultaneous identification of functional and morphological features of the presbyphagia, also in asymptomatic otherwise healthy elderly adults. This study retrospectively evaluated the effectiveness of the VFM and the role of a multidisciplinary team of specialists in the analysis of a large cohort of old patients with presbyphagia, with the objective of achieving early diagnosis of the disease and the best therapy to delay the development of complications such as aspiration pneumonia, malnutrition, and dehydration. PMID- 27392721 TI - Validation of DWI in assessment of radiotreated bone metastases in elderly patients. AB - Bone metastases are commonly observed in oncologic patients with advanced disease. These metastases are considered the main cause of neoplastic pain, with more than half of oncologic patients experiencing neoplastic pain during the course of the disease due to bone involvement. Lung, breast, and prostate cancers are the primary causes of bone metastases. Magnetic resonance imaging (MRI), especially diffusion weighted imaging (DWI) sequences, is the focus of our research, as it has been proven to be an optimal predictive index to assess the radiation treatment in many patients. We included patients treated with standard fractioning of radiation therapy. First, we examined the irradiated lesions with the MRI-DWI technique, before treatment and 30 and 60 days after its completion. Then we combined the MRI results and clinical parameters in a table with a predictive score for the quality of life in patients with bone metastases. This was a significant predictor of the efficacy of radiation treatment, from both clinical and psychological points of view, as it can allow an early assessment of the response to RT and therefore better scheduling of the next therapeutic steps to be performed. The table of the score we proposed helped guide patient monitoring, enabling us to undertake, where possible, follow-up with therapeutic strategies tailored to each patient's needs. PMID- 27392722 TI - Clinical evaluation of an over-the-counter hearing aid (TEO First(r)) in elderly patients suffering of mild to moderate hearing loss. AB - BACKGROUND: Presbycusis has a direct influence on autonomy of the elderly but hearing aids lack of affordability. Moreover a recent review demonstrate that electroacoustic characteristics of OTC hearing aids were generally not suitable for the elderly people. In our study, we assessed the clinical value of a new over-the-counter (OTC) hearing aid device (TEO First(r)) in the elderly. METHOD: This prospective monocentric open label study included patients over 60 years of age with a mild to moderate presbycusis. Patients were assessed with acceptable noise level test (ANL), pure tone (PTA) and speech (SA) audiometry in silent and noisy environment, with and without TEO First(r). A Glasgow Hearing Aid Benefit Profile, acceptability and satisfaction surveys were completed after one month of using the device. RESULTS: Thirty one patients were included. There was an improvement of hearing with TEO First(r) in silence (SA: +39.2 %, p < 0.01; PTA: 9.04 dB, p < 0.01) or in noise (SA +47.7 %, p < 0.01; PTA: -5.23 dB, p < 0.05). After one month of use of the device, quality of life has improved with regards to the following parameters: decrease of perceived hearing difficulties during conversation without background noise (-9.6 % p = 0.018), in conversation with several people (-16.2 % p = 0.0076), decrease of negative emotions while watching TV (-18.5 % p = 0.011), during conversation without background noise (-16.5 % p = 0.0024), during conversation in noisy background (-17.1 % p = 0.027) and during conversation with several people (-20 % p = 0.014). The acceptability of the device was low to moderate. CONCLUSION: TEO First(r) is an effective OTC hearing aid that improves the patient's quality of life. TRIAL REGISTRATION: Current Controlled Trials NCT01815788. PMID- 27392723 TI - [Not Available]. PMID- 27392724 TI - [Not Available]. PMID- 27392725 TI - [Not Available]. PMID- 27392726 TI - [Not Available]. PMID- 27392727 TI - [Not Available]. PMID- 27392728 TI - Child Anxiety Prevention Study: Impact on Functional Outcomes. AB - This study examined the impact of a selective anxiety prevention program for offspring of clinically anxious parents on three domains of child functioning: (1) social, (2) familial, and (3) emotional/behavioral. Dyads were randomized into either the Coping and Promoting Strength program (CAPS; n = 70) or Information Monitoring (IM; n = 66) comparison group. Multi-informant assessments were conducted at baseline, post intervention, and 6 and 12 months follow-ups. Random effects mixed models under the linear growth modeling (LGM) framework was used to assess the impact of CAPS on growth trajectories. Over time, children in the CAPS group had significantly lower anxiety, anxious/depressed symptoms, and lower total behavior problems (parent report), compared to children in IM group. The intervention did not impact other domains assessed (e.g., social functioning), which may be due to "floor effects" on these measures. Longitudinal follow-up data is needed to provide valuable information about this high risk population. PMID- 27392729 TI - Xenopus laevis Nkx5.3 and sensory organ homeobox (SOHo) are expressed in developing sensory organs and ganglia of the head and anterior trunk. AB - Nkx5 family members are homeobox transcription factors important for sensory organ development. Several members of the Nkx5 family are expressed in the eye, brain, developing ear, and lateral line. Members of this family have been previously identified in medaka, chick, and mouse. Here, we characterize two members of the Nkx5 family, Nkx5.3 and SOHo, in Xenopus laevis. We verify the identity of X. laevis Nkx5.3 and SOHo by phylogenetic comparison to chicken, medaka, and zebrafish orthologs. Both Nkx5.3 and SOHo are expressed in the developing eye, ear, lateral line system, and cranial neurons as determined by in situ hybridization. PMID- 27392730 TI - Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry. AB - Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX SPE). The dramatic suppression of background and chemical noise provided by DMS MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure. Graphical Abstract ?. PMID- 27392731 TI - Individual and community levels of maternal autonomy and child undernutrition in India. AB - OBJECTIVES: Investigate the relationship between maternal autonomy at multiple levels and the risk of child stunting, underweight, and wasting in India. METHODS: Data were from a 2005-2006 nationally representative, cross-sectional sample of 51,555 children under 5 years from 29 states in India. Multilevel, multivariable, logistic regression analyses were used to estimate the odds of child stunting, underweight, and wasting in relation to maternal autonomy in healthcare, movement, and money at the individual level and community level, while adjusting for several child, maternal, and household factors. RESULTS: When only adjusting for child age and sex, children in communities with a high proportion of women with autonomy in healthcare, or movement, or money, separately, had a lower risk of being stunted, underweight, or wasted, separately. However, adjusting for other explanatory factors attenuated these relationships and made them statistically insignificant. Individual maternal autonomy in any of the three domains was not associated with any of the outcomes. CONCLUSIONS: The results suggest that caution should be taken when interpreting the direct relevance of maternal autonomy at both individual and community levels to measures of child undernutrition. PMID- 27392732 TI - The consequences of coping with stalking-results from the first qualitative study on stalking in Denmark. AB - OBJECTIVES: The purpose of this article is to explore: (1) how victims of stalking experience the phenomenon in their daily life, (2) how the nature of stalking informs the victim's internal coping strategies, and (3) how the victims' internal coping strategies negatively affect their daily life and well being. METHODS: Qualitative semi-structured interviews were conducted with 25 victims of stalking. Thematic content analysis was employed, and themes were primarily identified inductively and broad into dialogue with concepts, such as Foucault's panopticism. RESULTS: The results of the study indicate that rather than the stalkers' harassment itself; it is the unpredictability of the stalkers' potential actions that inform the victims' primary coping strategy-self regulation. Self-regulation consists of various strategies victims employ to avoid the stalker. Our analysis shows that self-regulation as a coping strategy has social and psychological consequences for the victims, leading to various degrees of social isolation and apprehension. CONCLUSIONS: We conclude that it is necessary to consider how professionals advise victims to cope with their situation as how legal measures should focus on the security of victims. PMID- 27392734 TI - [Not Available]. AB - BACKGROUND: Failures may occur in each part of the medication use process. This study aimed to evaluate the barriers existing in hospital pharmacies in order to prevent medication errors and to help institutions to make improvement actions. METHODS: Within the framework of the SECURIMED project, risk assessment visit (interviews, observations, analysis of adverse event scenario by professionals...) were conducted in volunteer hospital pharmacies. A restitution meeting, after visit in each pharmacy permitted exchanges between visitors and professionals on barriers and weaknesses and then on solutions to reduce identified risks. RESULTS: Twenty-one hospital pharmacies participated. Despite presence of safeguards in some pharmacies, many weaknesses were retrieved (multiplicity of process, lack of resources...) and clinical pharmacy was not enough developed. CONCLUSION: This project has led to an overview of the situation in Aquitaine, and created a regional dynamic to improve the medication system safety. PMID- 27392733 TI - Trajectories for women who disclose intimate partner violence in health care settings: the key role of abuse severity. AB - OBJECTIVES: To examine the role of abuse severity in predicting women's trajectories in mental and physical health and psychological quality of life during the 18 months following abuse identification in a health care setting. METHODS: The present analysis used growth curve modeling in a sample of 411 women positive for abuse on the Composite Abuse Scale. RESULTS: A high proportion of women experienced severe combined abuse (SCA; 55 % at baseline and 29 % at 18 months). On average, there was an improvement in depressive symptoms and psychological quality of life over time. Controlling for sociodemographic characteristics, women scoring positive versus negative for SCA experienced increased depressive symptoms and decreased quality of life; however, exposure to severe abuse did not affect the rate of change over time in these outcomes. Severe abuse was not associated with physical health. CONCLUSIONS: There is an important association between abuse severity and women's health and well-being over time. Understanding the role of different abuse experiences, risk and protective factors, and trajectories can assist in more accurate identification and appropriate care provision for women exposed to IPV. PMID- 27392735 TI - [Toxic Epidermal Necrolysis Observed Shortly after the Introduction of a Treatment Including Celecoxib, Thiocolchicoside and Paracetamol]. PMID- 27392736 TI - [Polycystic Ovary Syndrome Induced by Valproic Acid. A Case Report]. PMID- 27392738 TI - [Not Available]. PMID- 27392737 TI - [Moderate Hyperlactatemia and Tendinitis. A Case Report in a Patient During Metformin and Antiretroviral Therapy]. PMID- 27392739 TI - Ecology of a tick-borne spotted fever in southern Brazil. AB - Rio Grande do Sul is the southernmost state of Brazil, bordering Uruguay. Clinical cases of spotted fever group (SFG) rickettsiosis were recently reported in Rio Grande do Sul. None of these cases was lethal, and all were confirmed by seroconversion to R. rickettsii antigens. Because serological cross-reactions are well known to occur between different SFG agents, the SFG agent responsible for the clinical cases remains unknown in Rio Grande do Sul, where no rickettsial agent is known to infect ticks. During 2013-2014, ticks and blood sera samples were collected from domestic dogs and wild small mammals, and from the vegetation in a SFG-endemic area of Rio Grande do Sul. Dogs were infested by Amblyomma ovale adult ticks, whereas small mammals were infested by immature stages of A. ovale, Ixodes loricatus, and adults of I. loricatus. Ticks collected on vegetation were adults of A. ovale, and immature stages of A. ovale, Amblyomma dubitatum, and Amblyomma longirostre. Three Rickettsia species were detected: Rickettsia bellii in I. loricatus, Rickettsia amblyommii in A. longirostre, and a Rickettsia parkeri-like agent (Rickettsia sp. strain Atlantic rainforest) in A. ovale. Seroreactivity to SFG antigens were detected in 19.7 % (27/137) canine and 37.5 % (15/40) small mammal sera, with highest titers to R. parkeri. Results indicate that the R. parkeri-like agent, strain Atlantic rainforest, is circulating between A. ovale ticks, dogs and small mammals in the study area, suggesting that this SFG pathogen could be one of the etiological agents of SFG clinical cases in Rio Grande do Sul. PMID- 27392740 TI - Hard ticks (Acari: Ixodidae) of livestock in Nicaragua, with notes about distribution. AB - We document the species of ticks that parasitize livestock in Nicaragua. The study was based on tick collection on cattle and horses from 437 farms in nine departments. Of 4841 animals examined (4481 cows and 360 horses), 3299 were parasitized, which represent 68 % of the bovines and 67 % of the equines in study: 59 cows and 25 horses were parasitized by more than one species. In addition, 280 specimens of the entomological museum in Leon were examined. The ticks found on cattle were Rhipicephalus microplus (75.2 % of the ticks collected), Amblyomma mixtum (20.8 %), A. parvum (2.6 %), A. tenellum (0.7 %), A. maculatum (0.7 %). While the ticks collected from the horses were: Dermacentor nitens (41.5 %), A. mixtum (31.7 %), R. microplus (13.8 %), A. parvum (6.5 %), A. tenellum (3.3 %), D. dissimilis (2.4 %) and A. maculatum (0.8 %). PMID- 27392741 TI - Increased immunity and BRAF inhibition: Yet another argument for combination therapy? PMID- 27392742 TI - Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials. AB - The aim of this meta-analysis was to evaluate the efficacy of curcuminoids supplementation on circulating concentrations of IL-6 in randomized controlled trials (RCTs). The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to November 01, 2015, to identify RCTs investigating the impact of curcuminoids on circulating IL-6 concentrations. Nine RCTs comprising 10 treatment arms were found to be eligible for the meta analysis. There was a significant reduction of circulating IL-6 concentrations following curcuminoids supplementation (WMD: -0.60pg/mL, 95% CI: -1.06, -0.14, p=0.011). Meta-regression did not suggest any significant association between the circulating IL-6 lowering effects of curcuminoids with either dose or duration of treatment. There was a significant association between the IL-6-lowering activity of curcumin and baseline IL-6 concentration (slope: -0.51; 95% CI: -0.80, -0.23; p=0.005). This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating IL-6 concentrations. This effect appears to be more evident in patients with higher degrees of systemic inflammation. PMID- 27392743 TI - Central dot sign. PMID- 27392744 TI - MDCT features of strangulated ileus due to an appendix epiploica of the sigmoid colon: four cases and a review of the literature. AB - PURPOSE: The aim of this study was to investigate the multidetector computed tomography (MDCT) features of strangulated ileus caused by epiploic appendix of the sigmoid colon. METHODS: We retrospectively evaluated MDCT images of four patients who underwent surgery in our hospital between 2011 and 2014. Patients were aged from 66 to 79 years, and two were female. RESULTS: Closed loop obstruction of the small bowel was confirmed in all patients. A fatty peritoneal band around the orifice of the ileus was detected in two patients, but was equivocal in the other two patients. Traction of the sigmoid colon toward the hilum of the closed loop of the small bowel was obvious in three patients. CONCLUSION: When traction of the sigmoid colon is detected in MDCT in a case of closed loop obstruction of the small bowel, strangulated ileus caused by an epiploic appendix should be considered in the differential diagnosis. PMID- 27392745 TI - Investigating the substrate binding mechanism of sulfotransferase 2A1 based on substrate tunnel analysis: a molecular dynamics simulation study. AB - Cytosolic sulfotransferases (SULTs) catalyze the transfer of a sulfonate group from the unique cofactor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a large number of diverse substrates. In this work, tunnels that facilitate the transport of substrates in the enzyme were studied, with and without bound cofactor, using extensive molecular dynamics simulations. Residues making up tunnels, as well as residues forming bottlenecks to the tunnels, were identified. Conformation analysis of the active-site cap was also performed. We found that binding of cofactor could significantly narrow the tunnel based on the closing of the active site cap to the enzyme. The roles of the key residues identified in this work deserve further exploration experimentally. PMID- 27392746 TI - Examination of the quality of various force fields and solvation models for the equilibrium simulations of GA88 and GB88. AB - Elucidating the relationship between sequence and conformation is essential for the understanding of functions of proteins. While sharing 88 % sequence identity and differing by only seven residues, GA88 and GB88 have completely different structures and serve as ideal systems for investigating the relationship between sequence and function. Benefiting from the continuous advancement of the computational ability of modern computers, molecular dynamics (MD) simulation is now playing an increasingly important role in the study of proteins. However, the reliability of MD simulations is limited by the accuracy of the force fields and solvent model approximations. In this work, several AMBER force fields (AMBER03, AMBER99SB, AMBER12SB, AMBER14SB, AMBER96) and solvent models (TIP3P, IGB5, IGB7, IGB8) have been employed in the simulations of GA88 and GB88. The statistical results from 19 simulations show that GA88 and GB88 both adopt more compact structures than the native structures. GB88 is more stable than GA88 regardless of the force fields and solvent models utilized. Most of the simulations overestimated the salt bridge interaction. The combination of AMBER14SB force field and IGB8 solvent model shows the best overall performance in the simulations of both GA88 and GB88. AMBER03 and AMBER12SB also yield reasonable results but only in the TIP3P explicit solvent model. PMID- 27392747 TI - Bioenergetic profiling of Trypanosoma cruzi life stages using Seahorse extracellular flux technology. AB - Energy metabolism is an attractive target for the development of new therapeutics against protozoan pathogens, including Trypanosoma cruzi, the causative agent of human Chagas disease. Despite emerging evidence that mitochondrial electron transport is essential for the growth of intracellular T. cruzi amastigotes in mammalian cells, fundamental knowledge of mitochondrial energy metabolism in this parasite life stage remains incomplete. The Clark-type electrode, which measures the rate of oxygen consumption, has served as the traditional tool to study mitochondrial energetics and has contributed to our understanding of it in T. cruzi. Here, we evaluate the Seahorse XF(e)24 extracellular flux platform as an alternative method to assess mitochondrial bioenergetics in isolated T. cruzi parasites. We report optimized assay conditions used to perform mitochondrial stress tests with replicative life cycle stages of T. cruzi using the XF(e)24 instrument, and discuss the advantages and potential limitations of this methodology, as applied to T. cruzi and other trypanosomatids. PMID- 27392748 TI - Aberrant Pattern of Cytokeratin Expression in Olfactory Neuroblastoma: A Potential Diagnostic Pitfall. PMID- 27392749 TI - Impurity-induced peroxidase mimicry of nanoclay and its potential for the spectrophotometric determination of cholesterol. AB - A green version of the "Fe" impurity-induced peroxidase mimicry exhibited by simple and cheap substrate "nanoclay (NC)" along with the highly sensitive amperometric and spectrophotometric determination of cholesterol is demonstrated. The "Fe" impurity can act as the catalyst center for hydrogen peroxide reduction similar to the horseradish peroxidase (HRP)-catalyzed reaction. The Michaelis Menten constant for the NC-catalyzed reaction is found to be lower than that of the HRP-catalyzed reaction indicating high affinity for the substrate. The NC modulated peroxidase-like catalytic activity originates from the electron transfer between the reducing substrate in the catalyst center and H2O2 with the intermediate generation of hydroxyl radicals. The peroxidase mimicry is successfully applied for the low-potential electrochemical detection of H2O2 (linear detection range 1.96-10.71 mM, R (2) = 0.97). The H2O2 sensing platform is further modified with cholesterol oxidase (CHOx) for the spectrophotometric (linear detection range 50-244 MUM, R (2) = 0.99) and amperometric detection of cholesterol (linear detection range 0.099-1.73 mM, R (2) = 0.998). Graphical abstract Peroxidase mimicry of nanoclay for the determination of cholesterol. PMID- 27392751 TI - Introduction to the Special Section: Positive Developmental Strategies for Engaging Emerging Adults and Improving Outcomes. PMID- 27392750 TI - A new sensitive and quantitative chemiluminescent assay to monitor intracellular xanthine oxidase activity for rapid screening of inhibitors in living endothelial cells. AB - Xanthine oxidase (XO) is an important enzyme, expressed at high levels in the vasculature in endothelial cells, that catalyzes the hydroxylation of hypoxanthine to xanthine and xanthine to uric acid. Excessive production of uric acid results in hyperuricemia linked to gout and cardiovascular diseases. Testing inhibition of XO is important for detection of potentially effective drugs or natural products that could be used to treat diseases caused by increased XO activity. In the present study, for the first time, we developed an in vitro chemiluminescent bioassay to determine XO activity in living endothelial cells and the IC50 value of oxypurinol, the active metabolite of the inhibitor drug allopurinol. Intracellular XO activity was measured in less than 20 min with a luminol/catalyst-based chemiluminescence assay able to measure XO with a limit of 0.4 MUU/mL. Oxypurinol addition to 5 * 103 cells (ranging from 5.0 to 0.0 MUM) caused a linear decrease in XO activity, with an IC50 of 1.0 +/- 0.5 MUM. The detection system developed was low-cost, rapid, reproducible, and easily miniaturizable so suitable to be used on small quantities of cells. PMID- 27392752 TI - aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities: a simplified auditing tool for community-acquired gastrointestinal surgical emergencies. AB - BACKGROUND: In a previous study, we found that Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) overpredicts morbidity risk in emergency gastrointestinal surgery. Our aim was to find a POSSUM equation adjustment. METHODS: A prospective observational study was performed on 2,361 patients presenting with a community-acquired gastrointestinal surgical emergency. The first 1,000 surgeries constituted the development cohort, the second 1,000 events were the first validation intramural cohort, and the remaining 361 cases belonged to a second validation extramural cohort. RESULTS: (1) A modified POSSUM equation was obtained. (2) Logistic regression was used to yield a statistically significant equation that included age, hemoglobin, white cell count, sodium and operative severity. (3) A chi-square automatic interaction detector decision tree analysis yielded a statistically significant equation with 4 variables, namely cardiac failure, sodium, operative severity, and peritoneal soiling. CONCLUSIONS: A modified POSSUM equation and a simplified scoring system (aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities [LUCENTUM]) are described. Both tools significantly improve prediction of surgical morbidity in community-acquired gastrointestinal surgical emergencies. PMID- 27392753 TI - Variations in hospitals costs for surgical procedures: inefficient care or sick patients? AB - BACKGROUND: Reducing unwanted variations has been identified as an avenue for cost containment. We sought to characterize variations in hospital costs after major surgery and quantitate the variability attributable to the patient, procedure, and provider. METHODS: A total of 22,559 patients undergoing major surgical procedure at a tertiary-care center between 2009 and 2013 were identified. Hierarchical linear regression analysis was performed to calculate risk-adjusted fixed, variable and total costs. RESULTS: The median cost of surgery was $23,845 (interquartile ranges, 13,353 to 43,083). Factors associated with increased costs included insurance status (Medicare vs private; coefficient: 14,934; 95% CI = 12,445.7 to 17,422.5, P < .001), preoperative comorbidity (Charlson Comorbidity Index = 1; coefficient: 10,793; 95% CI = 8,412.7 to 13,174.2; Charlson Comorbidity Index >=2; coefficient: 24,468; 95% CI = 22,552.7 to 26,383.6; both P < .001) and the development of a postoperative complication (coefficient: 58,624.1; 95% CI = 56,683.6 to 60,564.7; P < .001). Eighty-six percent of total variability was explained by patient-related factors, whereas 8% of the total variation was attributed to surgeon practices and 6% due to factors at the level of surgical specialty. CONCLUSIONS: Although inpatient costs varied markedly between procedures and providers, the majority of variation in costs was due to patient-level factors and should be targeted by future cost containment strategies. PMID- 27392754 TI - The changing pattern of diagnosing primary hyperparathyroidism in young patients. AB - BACKGROUND: Primary hyperparathyroidism (PHPT) is increasing in adults but rarely reported in young patients where routine blood work is obtained more judiciously. We aim to determine how PHPT is currently being diagnosed in young patients and examine surgical outcomes. METHOD: We retrospectively analyzed PHPT patients 24 years of age or less who underwent parathyroidectomy from 2001 to 2014. Patients were divided into 2 time periods: 2001 to 2007 (A) and 2008 to 2014 (B). Incidentally, diagnosed patients lacked objective symptoms of PHPT and had no family history. RESULTS: Forty young patients met inclusion criteria: 16 in group A and 24 in group B. Those in group A compared with group B had similar mean age, preoperative calcium, and parathyroid hormone (P > .05). Incidental diagnosis was more common in the contemporary group (42% vs 25%, P = .001). CONCLUSIONS: Current diagnosis of PHPT in young patients is increasingly incidental. This trend may be attributed to the more liberal use of labs in younger patients. PMID- 27392755 TI - The spatial reliability of task-irrelevant sounds modulates bimodal audiovisual integration: An event-related potential study. AB - The integration of multiple sensory inputs is essential for perception of the external world. The spatial factor is a fundamental property of multisensory audiovisual integration. Previous studies of the spatial constraints on bimodal audiovisual integration have mainly focused on the spatial congruity of audiovisual information. However, the effect of spatial reliability within audiovisual information on bimodal audiovisual integration remains unclear. In this study, we used event-related potentials (ERPs) to examine the effect of spatial reliability of task-irrelevant sounds on audiovisual integration. Three relevant ERP components emerged: the first at 140-200ms over a wide central area, the second at 280-320ms over the fronto-central area, and a third at 380-440ms over the parieto-occipital area. Our results demonstrate that ERP amplitudes elicited by audiovisual stimuli with reliable spatial relationships are larger than those elicited by stimuli with inconsistent spatial relationships. In addition, we hypothesized that spatial reliability within an audiovisual stimulus enhances feedback projections to the primary visual cortex from multisensory integration regions. Overall, our findings suggest that the spatial linking of visual and auditory information depends on spatial reliability within an audiovisual stimulus and occurs at a relatively late stage of processing. PMID- 27392756 TI - Candy Cane Appearance of the Esophagus Caused by Acute Thermal Injury. PMID- 27392757 TI - Inverse Association Between Poor Oral Health and Inflammatory Bowel Diseases. AB - BACKGROUND & AIMS: The hygiene hypothesis (a lack of childhood exposure to microorganisms increases susceptibility to allergic diseases by altering immune development) has been proposed as an explanation for the increasing incidence of inflammatory bowel disease (IBD). However, there are few data on the relationship between oral hygiene and development of IBD, and study results have been inconsistent. We investigated the association between poor oral health and risks of IBD, ulcerative colitis (UC), and Crohn's disease (CD). METHODS: We performed a population-based cohort study of 20,162 individuals followed for 40 years (from 1973 to 2012). Residents of 2 municipalities of Uppsala County, Sweden (N = 30,118), 15 years or older, were invited, and among them 20,333 were examined for tooth loss, dental plaques, and oral mucosal lesions at the time of study entry. Other exposure data were collected from questionnaires. Patients who later developed IBD (UC or CD) were identified by international classification codes from Swedish National Patient and Cause of Death Registers. Cox proportional hazards regression was used to estimate hazard ratios for IBD, UC, and CD. RESULTS: From National Patient and Cause of Death Registers, we identified 209 individuals who developed IBD (142 developed UC and 67 developed CD), with an incidence rate of 37.3 per 100,000 person-years. We found an inverse relationship between poor oral health and IBD, especially in individuals with severe oral problems. Loss of 5-6 teeth of the 6 teeth examined was associated with a lower risk of IBD (hazard ratio, 0.56; 95% confidence interval, 0.32-0.98). Having dental plaques that covered more than 33% of tooth surface was negatively associated with CD (hazard ratio, 0.32; 95% confidence interval, 0.10-0.97). CONCLUSIONS: In a population-based cohort study of more than 20,000 people in Sweden, we associated poor oral health with reduced risk of future IBD. PMID- 27392758 TI - A Case of Acute Esophageal Necrosis and Duodenal Disease in a Patient With Adrenal Insufficiency. PMID- 27392759 TI - Hepatitis due to Reactivation of Hepatitis B Virus in Endemic Areas Among Patients With Hepatitis C Treated With Direct-acting Antiviral Agents. AB - Hepatitis due to reactivation of hepatitis B virus (HBV) has been reported in patients treated with direct-acting antiviral (DAA) agents for chronic hepatitis C virus infection. We performed an observational study to determine the incidence of and factors associated with hepatitis in 327 patients receiving pan-oral DAA agents for HCV infections in areas endemic for HBV in China. Ten patients were positive for hepatitis B surface antigen (HBsAg), and 124 patients had occult HBV infection. HBV reactivation was determined by measuring HBV DNA and HBsAg status in serial serum samples collected every 2 weeks during DAA treatment and then every 4 weeks after treatment until week 12. In the total study population, 10 patients (3.1%) had hepatitis; 3 cases were associated with HBV reactivation (1 case not in the icteric phase, 1 case in the icteric phase, and 1 case with liver failure) and 7 from other causes. Testing positive for HBsAg before DAA treatment was a strong risk factor for developing hepatitis during treatment (hazard ratio, 15.0; P < .001). PMID- 27392760 TI - Systematic Review of Tumor Necrosis Factor Antagonists in Extraintestinal Manifestations in Inflammatory Bowel Disease. AB - BACKGROUND & AIMS: This systematic review investigated the efficacy and the effectiveness of biologic drugs in extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: Literature search was conducted in PubMed, Embase, and Cochrane until October 2015. Main inclusion criteria were adults with IBD, use of a biologic drug, evolution of EIMs, interventional study, or non-interventional study. RESULTS: Nine interventional studies (2 randomized controlled trials [N = 797], 7 open label trials [N = 1143], and 13 non interventional studies [N = 914]) were included. Tumor necrosis factor (TNF) antagonists achieved complete response for pyoderma gangrenosum in 21%-25% of patients in interventional studies and in 92%-100% patients in non-interventional studies, with similar results for other cutaneous manifestations such as erythema nodosum or stomatitis. Adalimumab significantly reduced the prevalence of anemia vs placebo after 56 weeks in 1 randomized controlled trial. In 2 non interventional studies, anti-TNF therapy improved anemia in the short-term (67%) and in the long-term (34%). Complete response after anti-TNF treatment was reported in interventional studies, including arthralgia (reduction in prevalence from 47.1% to 26.8% in the mid-term in 1 open label trial) and arthritis (reduction in prevalence from 8.7% to 2.1% and from 58% to 12.5% in 2 open label trials). Anti-TNFs were beneficial for a majority of patients with ocular manifestations. Infliximab was associated with improved outcomes in bone formation and bone mineral density. CONCLUSIONS: Anti-TNFs appear to be effective alternatives for certain EIMs associated with IBD including musculoskeletal, cutaneous, and ocular manifestations, and some beneficial effect may be obtained in metabolic bone disease and on hematologic or vascular EIMs. PMID- 27392761 TI - [Analysis of patient waiting times in a polyclinic for surgery]. AB - INTRODUCTION: Waiting times are a negative aspect for patients and therefore have a major influence on patient satisfaction. The aim of this research study was to evaluate waiting times from registration until first contact with a doctor in the outpatient department of the Polyclinic for Visceral, Thoracic and Vascular Surgery of the University Hospital Marburg. MATERIAL AND METHODS: Waiting times for 253 patients in the outpatient department were measured over a time period of 3 months. The mean age was 59.6 years (range 13-91 years). Patients were asked if they were satisfied with the waiting time and whether waiting time is a criterion in the choice of hospital. RESULTS: The mean waiting time of all 253 patients was 61 min, 48 (19 %) patients had to wait less than 15 min, 42 (16.6 %) patients 15 30 min, 57 (22.5 %) patients 30-60 min, 65 (25.7 %) patients 60-120 min, 36 (14.2 %) patients 120-240 min and 5 (2 %) patients had to wait 240-300 min. The mean waiting time was 109 min in the group of dissatisfied patients, whereas satisfied patients had a mean waiting time of 46 min (p = 0.000). We further evaluated patient satisfaction in correlation with waiting times at a cut-off of 30 min. Of the patients 163 had to wait more than 30 min whereby 106 (65 %) patients out of this group evaluated the waiting time as appropriate and 57 (35 %) as unsatisfactory. A total of 90 patients had to wait 30 min or less whereby 88 (97.8 %) patients out of this group were satisfied with the waiting time and 2 (2.2 %) were dissatisfied (p = 0.000). For 144 (56.9 %) out of the 253 patients the waiting time was a major criterion in the choice of hospital. CONCLUSION: Short waiting times play an important role in patient satisfaction and therefore represent a major competitive factor. From our results we concluded that a waiting time of 30 min should not be exceeded in order to maintain a high patient satisfaction. PMID- 27392762 TI - [Transparent operative training in visceral surgery : Analysis at a German university medical center]. AB - BACKGROUND: Practical operative training in the discipline of visceral surgery is currently under discussion. Aside from surveys, data on this topic in Germany are sparse. The aim of the study was an objective collation of surgical residents' practical training in the operating room in our department. METHODS: All surgical cases from 2015 were prospectively included. Procedures were stratified into resident and non-resident operations and complex cases with sub-steps which could potentially be performed by residents. We analyzed whether an operation or surgical sub-steps were performed by a resident. If this was not achieved, the reasons were analyzed. An anonymous online survey was conducted among employees in the surgery department regarding surgical training. RESULTS: Out of 2896 surgical cases 1141 (39.4 %) were classified as potential resident training operations, which were actually performed by a resident in 743 cases (65.1 %). The survey showed an underestimation of this proportion, where sub-steps were assisted in 30.3 % (n = 265) of 876 potential cases. This proportion significantly increased during the observation period (p < 0.001); however, it was highly overestimated by residents as well as fellows and senior consultants. Often organizational reasons were responsible when resident operations or sub steps were not performed by a trainee (13.1 % and 30.0 %, respectively). CONCLUSION: The monocentric analysis per se resulted in an improvement in practical surgical training. In the training environment, assisting with sub steps provides a great potential. Multicenter studies are needed. PMID- 27392763 TI - [Current standards of abdominal wall closure techniques : Conventional suture techniques]. AB - BACKGROUND: The most frequent complications following midline abdominal laparotomy include incisional hernias, which develop in 10-15 % of patients and surgical site infections in 15-25 % of cases; however, the risk of these complications can be reduced by the surgical technique and the use of special suture materials. In 2010, the INLINE meta-analysis performed by the Study Centre of the German Society of Surgery (SDGC) revealed that a continuous suture technique using slowly absorbable suture material resulted in the lowest risk of developing postoperative incisional hernia after elective midline laparotomy. OBJECTIVE: The aim of this study was to perform a systematic literature search to identify all randomized controlled trials (RCTs) that have been published since 2010 concerning conventional abdominal wall closure in order to update the 2010 INLINE meta-analysis and summarize current evidence. MATERIAL AND METHODS: On 28 January 2016, a systematic literature search was performed in MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL). All RCTs dealing with abdominal wall closure after midline laparotomy were identified and included for further analysis. RESULTS: Since 2010 a total of 9 RCTs comparing different techniques of abdominal wall closure have been published. Three monocentric RCTs comparing different suture materials, showed no significant differences to the INLINE meta-analysis regarding incisional hernia development; therefore, slowly absorbable sutures using a continuous suture technique are still recommended for abdominal wall closure in elective cases. Furthermore, six RCTs were identified which investigated antimicrobial suture materials but failed to show an overall advantage for Triclosan-coated suture material with respect to surgical site infections. CONCLUSION: Current evidence shows that slowly absorbable monofilament suture material using a continuous suture technique provides the best results with regard to incisional hernia rates after elective midline laparotomy. Triclosan-coated sutures cannot be recommended as a standard suture material as they failed to reduce surgical site infections. For emergency laparotomies no evidence exists to recommend a specific kind of suture technique or a special suture material. PMID- 27392764 TI - [Anorectal malignant melanoma : Treatment recommendations]. AB - BACKGROUND: Anorectal malignant melanoma is a rare tumor with a poor prognosis. Typical symptoms (bleeding, pain, perianal mass) are characteristic of hemorrhoids. This, together with the high rate of amelanotic tumors, often delays diagnosis. No therapy guidelines exist. MATERIALS AND METHODS: Based on our own experience of surgically treated patients and an extensive literature search, we present a stage-dependent therapeutic concept. RESULTS: Eight patients (six women) with a mean age of 65 +/- 8 years were treated at our institution. Six underwent abdominoperineal resection; two had local excision. Two patients additionally underwent inguinal lymph node dissection. Median survival was 12 months with a disease-free survival of 6 months. Forty treatment studies with a total of 1,970 cases could be identified. Prognostic factors are age, time to correct diagnosis, tumor extent, tumor stage, and perineural invasion. The impact of lymph node metastases and R0 resection varies. Surgery is the only effective therapy. Local excision is sufficient when free resection margins are achieved. CONCLUSIONS: Locally limited tumors should be resected; if possible using local excision. Larger tumors or tumors with sphincter infiltration often require abdominoperineal resection with curative intent. When regional lymph node metastases are present, we advise regional lymphadenectomy of the affected area. In the case of distant metastases, palliative surgery is needed for metastasectomy and in cases of incontinence or refractory pain. PMID- 27392765 TI - [A rare cause of ileus]. PMID- 27392766 TI - CORR Insights(r): Developing an Evidence-Based Followup Schedule for Bone Sarcomas Based on Local Recurrence and Metastatic Progression. PMID- 27392767 TI - CORR Insights((r)): Hip, Knee, and Ankle Osteoarthritis Negatively Affects Mechanical Energy Exchange. PMID- 27392768 TI - Transsacral Osseous Corridor Anatomy Is More Amenable To Screw Insertion In Males: A Biomorphometric Analysis of 280 Pelves. AB - BACKGROUND: Percutaneous iliosacral screw placement is the standard procedure for fixation of posterior pelvic ring lesions, although a transsacral screw path is being used more frequently in recent years owing to increased fracture-fixation strength and better ability to fix central and bilateral sacral fractures. However, biomorphometric data for the osseous corridors are limited. Because placement of these screws in a safe and effective manner is crucial to using transsacral screws, we sought to address precise sacral anatomy in more detail to look for anatomic variation in the general population. QUESTIONS/PURPOSES: We asked: (1) What proportion of healthy pelvis specimens have no transsacral corridor at the level of the S1 vertebra owing to sacral dysmorphism? (2) If there is no safe diameter for screw placement in the transsacral S1 corridor, is an increased and thus safe diameter of the transsacral S2 corridor expected? (3) Are there sex-specific differences in sacral anatomy and are these correlated with known anthropometric parameters? METHODS: CT scans of pelves of 280 healthy patients acquired exclusively for medical indications such as polytrauma (20%), CT angiography (70%), and other reasons (10%), were segmented manually. Using an advanced CT-based image analysis system, the mean shape of all segmented pelves was generated and functioned as a template. On this template, the cylindric transsacral osseous corridor at the level of the S1 and S2 vertebrae was determined manually. Each pelvis then was registered to the template using a free form registration algorithm to measure the maximum screw corridor diameters on each specimen semiautomatically. RESULTS: Thirty of 280 pelves (11%) had no transsacral S1 corridor owing to sacral dysmorphism. The average of maximum cylindrical diameters of the S1 corridor for the remaining 250 pelves was 12.8 mm (95% CI, 12.1-13.5 mm). A transverse corridor for S2 was found in 279 of 280 pelves, with an average of maximum cylindrical diameter of 11.6 mm (95% CI, 11.3 11.9 mm). Decreasing transsacral S1 corridor diameters are correlated with increasing transsacral S2 corridor diameters (R value for females, -0.260, p < 0.01; for males, -0.311, p < 0.001). Female specimens were more likely to have sacral dysmorphism (defined as a pelvis without a transsacral osseous corridor at the level of the S1 vertebra) than were male specimens (females, 16%; males, 7%; p < 0.003). Furthermore female pelves had smaller-corridor diameters than did male pelves (females versus males for S1: 11.7 mm [95% CI, 10.6-12.8 mm] versus 13.5 mm [95% CI, 12.6-14.4 mm], p < 0.01; and for S2: 10.6 mm [95% CI, 10.1-11.1 mm] versus 12.2 mm [95% CI, 11.8-12.6 mm ], p < 0.0001). CONCLUSIONS: Narrow corridors and highly individual, sex-dependent variance of morphologic features of the sacrum make transsacral implant placement technically demanding. Individual preoperative axial-slice CT scan analyses and orthogonal coronal and sagittal reformations are recommended to determine the prevalence of sufficient sized osseous corridors on both levels for safe screw placements, especially in female patients, owing to their smaller corridor diameters and higher rate of sacral dysmorphism. PMID- 27392769 TI - What Change in American Shoulder and Elbow Surgeons Score Represents a Clinically Important Change After Shoulder Arthroplasty? AB - BACKGROUND: The American Shoulder and Elbow Surgeons (ASES) questionnaire was developed to provide a standardized method for evaluating shoulder function. Previous studies have determined the clinical responsiveness of this outcome measure for heterogenous populations or patients with nonoperatively treated rotator cuff disease. Currently, to our knowledge, no studies exist that establish the clinically relevant change in the ASES score after shoulder arthroplasty. QUESTIONS/PURPOSES: We asked: (1) What are the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for the ASES score after primary and reverse shoulder arthroplasties? (2) Are the MCID and SCB for the ASES score different between primary and reverse shoulder arthroplasties? (3) What patient-related factors are associated with achieving the MCID and SCB after total shoulder arthroplasty and reverse shoulder arthroplasty? METHODS: A longitudinally maintained institutional shoulder arthroplasty registry was retrospectively queried for patients who underwent primary shoulder arthroplasty, including anatomic or reverse total shoulder arthroplasty from 2007 to 2013, with a minimum 2-year followup. Seven hundred ninety-four patients were identified and eligible; 304 of these patients did not have 2 years of followup or complete datasets, resulting in a study cohort of 490 patients (62% of the 794 potentially eligible). The MCID and SCB of the ASES score for these patients was calculated using an anchor-based method, using four different anchors measuring satisfaction with work, activities, overall, and activity from the SF-36. The MCID (anchored to somewhat satisfied) and SCB (very satisfied) of the ASES score were calculated for the entire cohort and stratified by arthroplasty type. Multivariate logistic regression of patient-related factors that influence the MCID and SCB achievement was performed. RESULTS: The MCID for all patients combined ranged from 6.3 to 13.5; for the overall satisfaction anchor, the MCID was 13.5 +/- 4.5 (95% CI, 4.8 22.3). The SCB for the overall cohort ranged from 12.0 to 36.6; for the overall satisfaction anchor, the SCB was 36.6 +/- 3.8 (95% CI, 29.1-44.1). There were no differences in the MCID of the ASES score between anatomic and reverse shoulder arthroplasty for any of the anchors (p = 0.159-0.992) or the SCB for any of the anchors (p = 0.467-0.977). Combining anatomic and reverse shoulder arthroplasty in one group, higher preoperative ASES score (odds ratio [OR], 0.96; 95% CI, 0.94 0.98; p < 0.001), having a reverse shoulder arthroplasty (OR, 0.36; 95% CI, 0.16 0.85; p = 0.016), and having rheumatoid arthritis were independent predictors of not achieving an MCID for the ASES 2 years after surgery. Higher preoperative ASES score (OR, 0.91; 95% CI, 0.89-0.92; p < 0.001), a diagnosis of rotator cuff tear arthropathy (OR, 0.14; 95% CI, 0.07-0.30; p < 0.001), a diagnosis of back pain (OR, 0.42; 95% CI, 0.24-0.71); p = 0.002), and living alone (OR, 0.36; 95% CI, 0.19-0.69; p = 0.002) were all independent predictors of not achieving SCB after shoulder arthroplasty. CONCLUSIONS: Patients with glenohumeral arthritis or rotator cuff tear arthropathy who undergo primary conventional total or reverse shoulder arthroplasty and have at least a nine-point improvement in their ASES score experience a clinically important change, whereas those who have at least a 23-point improvement in their ASES score experience a substantial clinical benefit. High preoperative function was associated with a decreased likelihood of achieving clinically important change after total shoulder arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27392770 TI - Charaterization and immunomodulatory activities of polysaccharide isolated from Pleurotus eryngii. AB - A water-soluble polysaccharide (EPA-1) from Pleurotus eryngii was obtained using DEAE-52 and Sephadex G-50 columns. The properties, structure and immunomodulatory activity of EPA-1 were studied. The results demonstrated that EPA-1 was a homogeneous polysaccharide with the molecular weight of 9.97*104Da. EPA-1 consisted of Man, Glc and Gal in a molar ratio of 2.2:1.0:3.2. The characterized fragment structures of EPA-1 were found to be consisting of seven sugar residues and two branches by GC-MS, FTIR and NMR analyses. Among them, the (1->6) linkedGal residue was the main linkage mode of EpA-1 and composed of its backbone. Activity tests indicated that EPA-1 significantly induced macrophage to release the immune activity factor of NO, TNF-alpha, IL-1 and IL-6 through activation of signal protein of p38, ERK, JNK in MAPKs and translocation of nuclear NF-kappaBeta, indicating EPA-1 to possess good immunoregulatory activity. PMID- 27392771 TI - Physical stability and rheological properties of konjac glucomannan-ethyl cellulose mixed emulsions. AB - Konjac glucomannan (KGM)/ethyl cellulose (EC) could form a stable homogeneous emulsion with appropriate mixing formula. This study aimed to investigate the stable mechanism of KGM/EC emulsion at different mixing ratio through its rheological properties, and droplet size and morphology changes with up to 6days storage time. Though emulsions samples with high KGM content had larger droplet size and worse uniformity at the fresh stage, they appeared to be more stable and droplets growth rate were slow during storage. Aggregation and morphology of droplets could be observed under confocal microscopy. Shear-thinning behavior were found in mixed emulsions, and mainly accredited to the KGM component. The effect of temperature on viscosities of the emulsions was well-described by Arrhenius equation. Increased KGM content led to larger storage modulus (G') and loss modulus (G"), and the difference in cross-over point of G' and G" implied changes in microstructures of the emulsions. PMID- 27392772 TI - Optimization & design of isradipine loaded solid lipid nanobioparticles using rutin by Taguchi methodology. AB - Our research objective was to optimize and design nano-biosystem of Isradipine (IDP) via novel bioenhancer (Rutin) loaded solid-lipid nanobioparticles (ANbp) using Taguchi design (TgD) methodology. Firstly, preliminary screening of solid lipid nanoparticles (SLNps) formulation core factors (A, B & C; Lipoid's, poly acid, sonication time respectively at fixed dose of model drug were assessed on entrapment efficiency & particle size; R1 & R2) by performed experimentally of three factor three levels orthogonal L27 array. Consequently, signal to noise (S/N) ratio plot of responses were drawn to predict better quality fitted-levels of significant factor for eminence optimization. Further, optimized quality spaces composition was used via enhancer (Rutin) to design advanced bio formulation (ANbp) and done its evaluation (entrapment efficiency, particle size, drug release & kinetics). As designed, ANbp results showed better sustained (86.54% as compared to control SLNps 94.48% in 24h) release, kinetics & stability behavior with good entrapment efficiency (97.58%) and desired smaller particle size (108nm). Therefore, statistically (TgD) optimization strategy would be considered to design nano-drug delivery system with bio-agent in-order to improve oral bioavailability of antihypertensive agents. PMID- 27392774 TI - Chitosan nanofiber production from Drosophila by electrospinning. AB - Drosophila melanogaster is one of the important test organisms in genetics thanks to its fast growth rate in a culture. This study demonstrates that the fly D. melanogaster can also be exploited as a source for nanofiber production in biotechnical applications. First, its chitin content was determined (7.85%) and then high molecular weight chitosan (141.4kDa) was synthesized through deacetylation of chitin isolates. Chitosan nanofibers with the diameter of 40.0073+/-12.347nm were produced by electrospinning of Drosophila chitosan. The physicochemical properties of obtained chitin and chitosan from D. melanogaster were determined by Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR). The study demonstrated that the fly D. melanogaster can be utilized for production of chitosan nanofiber concerning its cultivability and low-cost culture requirements. PMID- 27392773 TI - Development of amphoteric alginate/aminated chitosan coated microbeads for oral protein delivery. AB - A new amphoteric biopolymer carrier based on alginate and aminated chitosan coated microbeads (Alg/AmCS) was developed and characterized for bovine serum albumin (BSA) protein delivery. The amphoteric character was investigated through studying the swelling and in vitro BSA release behaviors of the developed microbeads in simulated gastric (SGF; pH1.2), intestinal (SIF; pH6.8), and colonic (SCF; pH7.4) fluids. The pH sensitivity was found to depend on the amount of AmCS in the coating medium. The results were interpreted from the view of the individual pH sensitivity of alginate and aminated chitosan in addition to the ionic interaction between them under the studied pHs. Besides; it was found that the BSA loading efficiency (LE) exceeded 82% regardless of the initial concentration of BSA. The released amount of BSA reached approximately 63% and 86% in SIF and SCF, respectively, using 0.25% AmCS. The stability of alginate microbeads in SCF was improved with increasing AmCS concentration in the coating medium up to 2%. Furthermore, the developed microbeads demonstrated their ability for biodegradation in addition to their antibacterial activities against selected bacterial strains. The results clearly suggested that Alg/AmCS coated microbeads could be suitable carriers for site-specific protein delivery in the intestinal and colon tracts. PMID- 27392775 TI - Pullulan-based coatings for preservation of razor clam Sinonovacula constricta. AB - Glutathione has antioxidant activity, and citric acid exhibits acidity. Potassium sorbate displays antibacterial activity. Effects of pullulan-based coatings with 0.05% glutathione, 0.5% citric acid and 0.2% potassium sorbate on the preservation of razor clam Sinonovacula constricta meats (SCMs) during refrigerated storage (~2 degrees C) were investigated. The glutathione-, citric acid- and potassium sorbate-incorporated pullulan-based coatings inhibited bacterial growth. Moreover, results showed reduced increase in pH, decreased total volatile basic nitrogen and enhanced overall acceptability score of SCMs during refrigerated storage (~2 degrees C). These results indicated that treatment with pullulan-based coatings with glutathione, citric acid and potassium sorbate could prolong the shelf life of SCM for up to 10 days. PMID- 27392776 TI - Lipase of Bacillus stratosphericus L1: Cloning, expression and characterization. AB - Present work was undertaken to discover new lipolytic enzymes as well as novel bacterial strains for applications in biotechnology. One of the isolated strains identified as Bacillus stratosphericus L1 produced extracellular lipase (LipBST) which was cloned and expressed in Escherichia coli. Purified mature enzyme had a molecular mass of 19kDa. Recombinant protein showed an activity of 6244.5U/mg at pH 9, 35 degrees C. It was stable in the range of 35-55 degrees C and retained more than 60% activity after incubation for 4h. LipBST was activated by organic solvents such as acetone and n-hexane. Lipase was inactivated by all investigated metal ions, inhibitors and detergents. LipBST was determined to be short-chain specific, but also hydrolyzed medium-, long-chain p-nitrophenyl and natural fatty substrates. The values of Vmax and KM for p-nitrophenyl butyrate, p-nitrophenyl caprylate, p-nitrophenyl decanoate were 1.1, 2.5, 0.1mMmin-1 and 5*10-2, 3.4*10 2, 194*10-2mM, respectively. Biochemical characteristics of LipBST suggest a great potential for various biotechnological applications including detergent formulation, bioremediation and organic synthesis processes. PMID- 27392777 TI - Purification and characterization of laccase from Sinorhizobium meliloti and analysis of the lacc gene. AB - The soil native bacterial strains were screened for laccase activity. Bacterial strain L3.8 with high laccase activity was identified as Sinorhizobium meliloti. The crude intracellular L3.8 enzyme extract was able to oxidize typical diagnostic substrates of plant and fungal laccases. Laccase L3.8 was purified 81 fold with a yield of 19.5%. The molecular mass of the purified bacterial laccase was found to be 70.0kDa and its pI was 4.77. UV-vis spectrum showed that L3.8 protein is a multicopper oxidase. The carbohydrate content of the purified enzyme was estimated at 3.2%. Moreover, the laccase active fraction was characterized in terms of kinetics, temperature, and pH optima as well as the effect of various chemical compounds on the laccase activity, and antioxidant properties, which indicated that the L3.8 laccase had unique properties that might be important in biotechnological applications. The lacc gene encoding S. meliloti laccase was cloned and characterized. The full-length sequence of 1950bp encoded a protein of 649 aa preceded by a signal peptide consisting of 26aa. Laccase L3.8 shared significant structural features characteristic of other laccases, including the conserved regions of four histidine-rich copper-binding sites. Potential biotechnological importance of a newly identified laccase is discussed. PMID- 27392778 TI - Risk factors for clinical anastomotic leakage after right hemicolectomy. AB - PURPOSE: Anastomotic leakage (AL) after right hemicolectomy is a devastating complication, and risk factors for AL in this setting are rarely investigated exclusively. Recent reports suggest that anastomotic type may influence the rate of AL in ileocolic anastomoses. We investigated risk factors and short-term outcomes in patients subjected to right hemicolectomy. METHODS: Data from all patients undergoing right hemicolectomy at our institution between 2009 and 2013 were collected in a database. Risk factors for clinical AL, 30-day mortality, hospital and intensive care unit stay were investigated. Stepwise logistic regression was used to adjust for confounding. RESULTS: 22/445 (4.9 %) patients had AL. Median time to AL was 6 days (range 2-11 days). A stapled anastomosis was associated with an increased AL rate compared with the handsewn approach (adjusted odds ratio (aOR) 2.84; 95 % CI 1.14-7.07; P = 0.025). Other risk factors for AL were tobacco use (aOR 2.70; 95 % CI 1.06-6.86; P = 0.037) and diabetes (aOR 5.95; 95 % CI 2.23-15.90; P < 0.001). Anastomotic ischemia was present in 6/13 stapled and 1/9 handsewn leaking anastomoses, P = 0.081, while generalized peritonitis was observed after 4/13 stapled and 7/9 handsewn leaking anastomoses, P = 0.030. Thirty-day mortality was 2/22 (9.1 %) in patients with AL and 23/423 (5.4 %) in patients without AL, P = 0.468, and 13/160 (8.1 %) and 12/285 (4.2 %), P = 0.085, in stapled and handsewn anastomoses, respectively. CONCLUSIONS: Risk factors for AL after right hemicolectomy were diabetes, tobacco use and stapled compared with handsewn anastomoses. PMID- 27392779 TI - Iatrogenic superior mesenteric vein injury: the perils of high ligation. AB - PURPOSE: The purpose of this review is to highlight the perils and pitfalls associated with high vascular ligation during right colectomies for adenocarcinoma and to identify the various mechanisms of injury to the superior mesenteric vein (SMV) and its tributaries. METHODS: This is a retrospective chart review of 304 right colectomies (159 open and 145 laparoscopic) performed over a period of 10 years (1 June 2006-31 May 2016) for right-sided colonic adenocarcinoma in an academic medical center. RESULTS: During a 10-year study period, we encountered five cases in which significant damage to the SMV and its tributaries occurred. This accounts for a total of 1.6 % of all right colectomies performed for colonic adenocarcinoma. CONCLUSIONS: Iatrogenic superior mesenteric vein injury is a rare, severe, and underreported complication of both open and laparoscopic right colectomy for colonic adenocarcinoma. We identified several mechanisms of injury such as anatomic misperception, excessive traction and pulling on the venous system, extensive tumor involvement of the mesentery, and uncontrolled suturing attempts at hemostasis. We believe that increased awareness of this complication with profound understanding of vascular anatomy and the different mechanisms of injury will allow surgeons to avoid this often devastating complication. PMID- 27392780 TI - [Not Available]. PMID- 27392782 TI - Occupational Asthma Due to Inhalation of Aerosolized Lipophilic Coating Materials. AB - We present a case of onset of severe asthma in a 59-year-old patient who worked in an aerospace plant. He was noted to have wheezing on exam and obstruction on PFTs. Review of his occupational history revealed exposure to lipophilic industrial compounds. We outline the radiographic and histologic findings that were found in the patient, and discuss occupational asthma due to inhalation of lipophilic compounds. PMID- 27392781 TI - The role of contact chemoreception in the host location process of an egg parasitoid. AB - Taste allows insects to detect palatable or toxic foods, identify a mate, and select appropriate oviposition sites. The gustatory system strongly contributes to the survival and reproductive success of many species, yet it is rarely studied in insect parasitoids. In order to locate and assess a host in which they will lay their eggs, female wasps actively search for chemical cues using their sensory organs present mainly on the antennae. In this paper, we studied the role of antennal taste sensilla chaetica in the perception of contact semiochemicals in Trissolcus brochymenae (Hymenoptera: Platygastridae), an egg parasitoid of the brassicaceae pest Murgantia histrionica (Heteroptera: Pentatomidae). Methanolic extracts obtained from male and female hosts elicited action potentials in taste neurons housed in antennal sensilla chaetica, indicating that these sensilla are involved in the perception of non volatile host kairomones. In behavioural assays, wasp females displayed an intense searching behaviour in open arenas treated with host extracts, thus confirming that these kairomones are soluble in polar solvents. We further investigated the extracts by Gas Chromatography-Mass Spectrometry (GC-MS) and found that they contain several compounds which are good candidates for these contact kairomones. This study contributes to better understanding contact chemoreception in egg parasitoids and identifying gustatory receptor neurons involved in the host location process. PMID- 27392783 TI - Assessing Community Coalition Capacity and its Association with Underage Drinking Prevention Effectiveness in the Context of the SPF SIG. AB - Community coalitions are a prominent organizational structure through which community-based substance abuse prevention efforts are implemented. There is little empirical evidence, however, regarding the association between coalition attributes and success in achieving community-level reductions in substance abuse behaviors. In this study, we assessed the relationship between coalition capacity, based on coalition coordinator responses to 16 survey items, and reductions in underage drinking prevalence rates. The coalitions were funded through the federally sponsored Strategic Prevention Framework State Incentive Grant (SPF SIG). We first examined whether coalition capacity increased over the life of the projects. Mean capacity scores increased for all 16 capacity items examined (N = 318 coalitions), the majority of which were statistically significant. Analysis of the associations between capacity and reductions in underage drinking was limited to coalitions that targeted underage drinking and provided usable outcome measures based on student survey data for either past 30 day alcohol use (N = 129) or binge drinking (N = 100). Bivariate associations between the capacity items and prevalence reductions for each outcome were consistently positive, although many were not statistically significant. Composite measures of correlated items were then created to represent six different capacity constructs, and included in multivariate models to predict reductions in the targeted outcomes. Constructs that significantly predicted reductions in one or both outcome measures included internal organization and structure, community connections and outreach, and funding from multiple sources. The findings provide support for the expectation that high functioning community coalitions can be effective agents for producing desirable community-level changes in targeted substance abuse behaviors. PMID- 27392784 TI - [Not Available]. AB - The concept of heart failure with preserved left ventricular ejection fraction has replaced that of diastolic heart failure. It is today the most frequent presentation of heart failure because of the progressive aging of the population. Its prognosis appears to be similar to that of heart failure with reduced systolic function. B type natriuretic peptide dosing as well as doppler echocardiography are useful for the diagnosis. Today, no treatment has revealed effective but clinical trials have been scarce. Renin-angiotensin system antagonists have promising properties but haven't shown efficacy. This article reviews the epidemiologic, diagnostic, pathophysiologic and therapeutic aspects of the disease. PMID- 27392786 TI - Discrepancy between genotypic and phenotypic extended-spectrum beta-lactamase rates in Escherichia coli from intra-abdominal infections in the USA. AB - Varying rates of false-positive results of phenotypic extended-spectrum beta lactamase (ESBL) tests have been reported for different methods in different settings, species and geographic locations. This report describes discrepancies in Escherichia coli genotypic and phenotypic ESBL rates observed in a surveillance study of 29 US hospitals that participated in the Study for Monitoring Antimicrobial Resistance Trends (SMART). The ESBL phenotype was determined with the Clinical and Laboratory Standards Institute confirmatory broth microdilution test using cefotaxime and ceftazidime with and without clavulanate. Genes encoding ESBLs, carbapenemases and plasmidic AmpC beta lactamases were detected using a combination of microarray and multiplex PCR assays. Among 168 molecularly characterized phenotypically ESBL-positive E. coli isolates from intra-abdominal infections, 4.8 % were genotypically negative from 2009 to 2012 and 29.5 % in 2013. Because of the high rate of false-positive phenotypic ESBL results in 2013, the 5-year phenotypic ESBL trend was skewed and showed a statistically significant increase (P<0.05) in ESBL-positive E. coli in the USA, which was not seen using the genotypic ESBL rates. The majority of false positive phenotypic profiles had ceftazidime MICs of 2 ug ml-1 and a >=3 doubling dilution decrease in MIC for only one of the two antimicrobial agents. False positive ESBL results can adversely impact epidemiological surveillance and patient care (including inappropriate treatment, unnecessary patient isolation and higher costs). Careful evaluation and comparison of phenotypic and genotypic test results can yield the greatest insight, but the most accurate (and faster) detection of ESBL producers is usually based on molecular data. PMID- 27392787 TI - Pseudodesulfovibrio indicus gen. nov., sp. nov., a piezophilic sulfate-reducing bacterium from the Indian Ocean and reclassification of four species of the genus Desulfovibrio. AB - A novel sulfate-reducing bacterium, strain J2T, was isolated from a serpentinized peridotite sample from the Indian Ocean. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain J2T clustered with the genus Desulfovibrio within the family Desulfovibrionaceae, but it showed low similarity (87.95 %) to the type species Desulfovibrio desulfuricans DSM 642T. It was most closely related to Desulfovibrio portus MSL79T (96.96 %), followed by Desulfovibrio aespoeensis Aspo-2T (96.11 %), Desulfovibrio piezophilus C1TLV30T (96.04 %) and Desulfovibrio profundus DSM 11384T (95.17 %). Other available sequences shared less than 93.33 % 16S rRNA gene sequence similarity. Cells were Gram-staining negative, anaerobic, motile vibrios (2-6*0.4-0.6 um). Growth was observed at salinities ranging from 0.2 to 6 % (optimum 2.5 %), from pH 5 to 8 (optimum pH 6.5-7) and at temperatures between 9 and 40 degrees C (optimum 30-35 degrees C). J2T was piezophilic, growing optimally at 10 MPa (range 0-30 MPa). J2T used lactate, malate, pyruvate, formate and hydrogen as energy sources. Sulfate, thiosulfate, sulfite, fumarate and nitrate were used as terminal electron acceptors. Lactate and pyruvate were fermented. The main fatty acids were iso-C15 : 0, anteiso-C15 : 0, summed feature 9 (iso-C17 : 1omega9c and/or C16 : 0 10 methyl) and iso-C17 : 0. The DNA G+C content of strain J2T was 63.5 mol%. The combined genotypic and phenotypic data show that strain J2T represents a novel species of a novel genus in the family Desulfovibrionaceae, for which the name Pseudodesulfovibrio indicus gen. nov., sp. nov. is proposed, with the type strain J2T (=MCCC 1A01867T = DSM 101483T). We also propose the reclassification of D. piezophilus as Pseudodesulfovibrio piezophilus comb. nov., D. profundus as Pseudodesulfovibrio profundus comb. nov., D. portus as Pseudodesulfovibrio portus comb. nov. and D. aespoeensis as Pseudodesulfovibrio aespoeensis comb. nov. PMID- 27392788 TI - Push-Pull: Chemical Ecology-Based Integrated Pest Management Technology. AB - Lepidopterous stemborers, and parasitic striga weeds belonging to the family Orobanchaceae, attack cereal crops in sub-Saharan Africa causing severe yield losses. The smallholder farmers are resource constrained and unable to afford expensive chemicals for crop protection. The push-pull technology, a chemical ecology- based cropping system, is developed for integrated pest and weed management in cereal-livestock farming systems. Appropriate plants were selected that naturally emit signaling chemicals (semiochemicals). Plants highly attractive for stemborer egg laying were selected and employed as trap crops (pull), to draw pests away from the main crop. Plants that repelled stemborer females were selected as intercrops (push). The stemborers are attracted to the trap plant, and are repelled from the main cereal crop using a repellent intercrop (push). Root exudates of leguminous repellent intercrops also effectively control the parasitic striga weed through an allelopathic mechanism. Their root exudates contain flavonoid compounds some of which stimulate germination of Striga hermonthica seeds, such as Uncinanone B, and others that dramatically inhibit their attachment to host roots, such as Uncinanone C and a number of di-C-glycosylflavones (di-CGFs), resulting in suicidal germination. The intercrop also improves soil fertility through nitrogen fixation, natural mulching, improved biomass, and control of erosion. Both companion plants provide high value animal fodder, facilitating milk production and diversifying farmers' income sources. The technology is appropriate to smallholder mixed cropping systems in Africa. Adopted by about 125,000 farmers to date in eastern Africa, it effectively addresses major production constraints, significantly increases maize yields, and is economical as it is based on locally available plants, not expensive external inputs. PMID- 27392789 TI - External Validation of Triple D Score in an Elderly (>=65 Years) Population for Prediction of Success Following Shockwave Lithotripsy. AB - INTRODUCTION: Triple D score was recently developed for prediction of extracorporeal shockwave lithotripsy (SWL) outcomes. However, it has not been validated. SWL in elderly patients results in lower success and higher complication rates. We aimed at externally validating Triple D score in a population >=65 years of age. PATIENTS AND METHODS: We retrospectively analyzed the data of 182 patients >=65 years of age who underwent SWL for renal or ureteral stones and were evaluated with non-contrast computed tomography before SWL. Stone volume (SV), skin-to-stone distance (SSD), and stone density were measured, and cutoff values were determined with receiver operator characteristic analysis. Triple D scores were calculated, and success rates were determined for each score. RESULTS: Mean SV, SSD, and stone density values were significantly higher in patients with failed outcomes compared with those with successful outcomes in both renal and ureteral cases. Cutoff values of 187.5 mm(3), 10.5 cm, and 675 HU for renal stones and of 185 mm(3), 11.5 cm, and 785 HU for ureteral stones were detected. Success rates of 95.5% and 95% were detected for patients with a Triple D score of 3 in the renal and ureteral stone groups, respectively. Success rates of patients with a Triple D score of 0 were 20% and 25% in the renal and ureteral stone groups, respectively. CONCLUSIONS: Triple D score correlated well with SWL outcomes in patients >=65 years of age, and it is externally validated. Various factors may deal with cutoff levels of involved parameters. Therefore, we suggest that each institution determines its unique cutoff levels for SV, SSD, and stone density parameters and calculates the Triple D score for its patients with respect to these cutoff levels to predict the success after SWL and aid in decision making. PMID- 27392790 TI - Phase 1 study to evaluate the effect of the MEK inhibitor trametinib on cardiac repolarization in patients with solid tumours. AB - PURPOSE: Trametinib is a reversible, selective inhibitor of the mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and 2 (MEK2). Cardiotoxicity (congestive heart failure, decreased heart rate, left ventricular dysfunction, and hypertension) related to trametinib is an infrequent, but serious, adverse event (AE). Prolongation of the QT interval increases the risk of life threatening cardiac arrhythmia. Thus, the risk of trametinib inducing QT prolongation at putative supratherapeutic exposure was evaluated. METHODS: Eligible patients with solid tumours received placebo on day 1, once-daily trametinib 2-mg doses on days 2-14, and a single trametinib 3-mg dose on day 15 to achieve supratherapeutic dosing for QTc measurement. Electrocardiogram was assessed by 12-lead ambulatory 24-h Holter monitoring pre-dose, and on day 1 and day 15. Pharmacokinetic (PK) and pharmacodynamics (PD) parameters were measured. RESULTS: Thirty-two of 35 patients completed the study. There was no effect of trametinib when compared with time-matched placebo on the change from baseline in QTcF, QTcB, or QTcI interval. Mean AUC0-24 and C max following trametinib 2-mg repeat doses were 364 ng.h/mL and 22.9 ng/mL, respectively; the corresponding values for the 3-mg dose were 454 ng.h/mL and 29.2 ng/mL. Median T max was approximately 2 h for both doses. Statistical analysis and PK/PD modelling showed no significant relationship between QTcF interval and trametinib plasma concentrations. AEs were consistent with those reported previously. No electrocardiogram abnormalities were reported as AEs. CONCLUSIONS: The results of this study suggest trametinib has no significant effect on QT prolongation at supratherapeutic exposure. PMID- 27392791 TI - Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways. AB - Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents' high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period. PMID- 27392793 TI - Small-Molecule Induction of Canine Embryonic Stem Cells Toward Naive Pluripotency. AB - Naive and primed pluripotent stem cells (PSCs) reflect discrete pluripotent states that approximate the inner cell mass or the progressively lineage restricted perigastrulation epiblast, respectively. Cells that occupy primed pluripotency have distinct epigenetic landscapes, transcriptional circuitry, and trophic requirements compared with their naive counterparts. The existence of multiple pluripotent states has not been explored in dogs, which show promise as outbred biomedical models with more than 300 inherited diseases that also afflict humans. However, our understanding of canine embryogenesis and embryo-derived stem cells is limited. Herein, we converted leukemia inhibitory factor (LIF) dependent and fibroblast growth factor 2 (FGF2)-dependent canine embryonic stem cells (cESCs) resembling primed PSCs toward a naive pluripotent state using LIF and inhibitors of glycogen synthase kinase 3beta and mitogen-activated protein kinase kinase 1/2 [called 2i and LIF (2iL)]. cESCs propagated in 2iL exhibited significant induction of genes associated with the naive pluripotent state (eg, REX1, TBX3) and downregulation of primed pluripotency markers (eg, OTX2, FGF5) (P < 0.05). Differential phosphorylation of signal transducer and activator of transcription 3 (STAT3) and cell fate decisions on exposure to bone morphogenetic protein 4 (BMP4) suggested that a novel pluripotent identity has been established with 2iL. Accordingly, cESCs cultured with 2iL formed colonies at a greater efficiency than LIF-FGF2 cESCs following single-cell dissociation. Total genomic DNA methylation and histone H3 lysine 27 trimethylation signals were reduced in 2iL-treated cESCs. Our data suggest that 2iL culture conditions promote the conversion of cESCs toward an epigenetically distinct pluripotent state resembling naive PSCs. PMID- 27392794 TI - Taking Stock and Moving Forward: Research on Asian American Child Development. AB - With this Special Section, the Asian Caucus of the Society for Research in Child Development seeks to promote a more inclusive, expanded, and holistic developmental science that can account for the diversity of developmental trajectories among Asian Americans. The articles elucidate, in turn, historical, conceptual, and methodological issues in studying Asian American child development. Although the articles foreground Asian Americans, the ideas should help advance theoretical and empirical work for other racial and ethnic groups, thereby contributing to a more valid understanding of child development. PMID- 27392792 TI - Gray matter volume and dual-task gait performance in mild cognitive impairment. AB - Dual-task gait performance is impaired in older adults with mild cognitive impairment, but the brain substrates associated with dual-task gait performance are not well-established. The relationship between gray matter and gait speed under single-task and dual-task conditions (walking while counting backward) was examined in 560 seniors with mild cognitive impairment (non-amnestic mild cognitive impairment: n = 270; mean age = 72.4 yrs., 63.6 % women; amnestic mild cognitive impairment: n = 290; mean age = 73.4 yrs., 45.4 % women). Multivariate covariance-based analyses of magnetic resonance imaging data, adjusted for potential confounders including single-task gait speed, were performed to identify gray matter patterns associated with dual-task gait speed. There were no differences in gait speed or cognitive performance during dual-task gait between individuals with non-amnestic mild cognitive impairment and amnestic mild cognitive impairment. Overall, increased dual-task gait speed was associated with a gray matter pattern of increased volume in medial frontal gyrus, superior frontal gyrus, anterior cingulate, cingulate, precuneus, fusiform gyrus, middle occipital gyrus, inferior temporal gyrus and middle temporal gyrus. The relationship between dual-task gait speed and brain substrates also differed by mild cognitive impairment subtype. Our study revealed a pattern of gray matter regions associated with dual-task performance. Although dual-task gait performance was similar in amnestic and non-amnestic mild cognitive impairment, the gray matter patterns associated with dual-task gait performance differed by mild cognitive impairment subtype. These findings suggest that the brain substrates supporting dual-task gait performance in amnestic and non-amnestic subtypes are different, and consequently may respond differently to interventions, or require different interventions. PMID- 27392795 TI - Placing Asian American Child Development Within Historical Context. AB - This article discusses influences of historical time and place on the development of children and youth of Asian descent in the U.S. Chinese, Indian, Hmong, and Filipino American experiences illustrate how history has defined race and racial stereotypes, determined cultural and community contexts, established pre /postmigration circumstances, and influenced oppression and discrimination. Cross cutting issues as applied to other ethnicities are discussed. By recognizing history's reach on child development, this article intends to inspire others to acknowledge and consider historical influences in their work. It also lays a foundation for the two ensuing articles within this Special Section, which present a novel conceptual framework (Mistry et al., this volume) and methodological recommendations (Yoshikawa, Mistry, & Wang, this volume) for research. PMID- 27392796 TI - An Integrated Conceptual Framework for the Development of Asian American Children and Youth. AB - The diversity of circumstances and developmental outcomes among Asian American children and youth poses a challenge for scholars interested in Asian American child development. This article addresses the challenge by offering an integrated conceptual framework based on three broad questions: (a) What are theory predicated specifications of contexts that are pertinent for the development of Asian American children? (b) What are the domains of development and socialization that are particularly relevant? (c) How can culture as meaning making processes be integrated in conceptualizations of development? The heuristic value of the conceptual model is illustrated by research on Asian American children and youth that examines the interconnected nature of specific features of context, pertinent aspects of development, and interpretive processes. PMID- 27392797 TI - Advancing Methods in Research on Asian American Children and Youth. AB - Asian American children and youth constitute at the same time an immigrant group, a set of ethnic groups, and a set of cultural groups. Research on these populations can therefore take on one or more of these perspectives. This article provides guidance for research methods in three areas: (a) conceptualizing and assessing migration-related factors, (b) assessing ethnicity and national origin, and (c) using culturally and contextually relevant measures. Methodological recommendations are made for each area, with attention to small-scale studies with community samples as well as large-scale data sets. In addition, this article recommends researchers attend to within-group variations (i.e., intersections of ethnicity, generational status, gender, class, sexuality), the embeddedness of individual development in context, and specificity of developmental periods. PMID- 27392798 TI - Commentary: Advancing Our Understanding of Asian American Child Development: History, Context, and Culture as Essential Considerations. AB - The Special Section will help scholars make informed choices about how to conceptualize developmental processes and assess contextually and culturally relevant variables in future research with Asian American children and youth. It undertakes tasks and addresses challenges that have broad relevance to the study of developmental processes and stands as a reminder of the vital role of interdisciplinary perspectives in the advancement of developmental science. PMID- 27392799 TI - Commentary: Charting Future Directions for Research on Asian American Child Development. AB - Asian Americans are now the fastest growing ethnic minority group in the United States, but developmental research on them lags behind that of African Americans and Latinos. It is advocated that developmental scientists working with Asian American families focus on early developmental processes, on the cultural aspects of family socialization and dynamics that may contribute to child outcomes, and on capturing the complexity of factors that promote cultural adaptation and strengths in particular contexts. The theoretical frameworks, methodological recommendations, and timely themes highlighted in this special issue will motivate scholars, interventionists, and policymakers to find ways to better understand and meet the needs of the growing number of Asian American children and their families. PMID- 27392800 TI - Commentary: An Asian Americanist Perspective on Child Development. AB - In this commentary, we put forth an Asian Americanist perspective on child development that frames, expands upon, and at times challenges the contextual, conceptual, and methodological ideas put forward by Kiang et al., Mistry et al., and Yoshikawa et al. (this volume). This Asian Americanist perspective draws upon scholarship in Asian American Studies and critical race theory to bridge the historical, conceptual, and methodological contributions of the three articles. We also aim to challenge current and future generations of scholars studying Asian American child development to look at Asian American youth and families as autonomous, self-determining agents who are capable of challenging, resisting, and affecting change in a racialized society. PMID- 27392801 TI - Response to Commentaries on Taking Stock and Moving Forward: Research on Asian American Child Development. AB - We briefly respond here to the commentaries to the Special Section focused on Asian American child development by Cheah, Lee, Beaupre, and Zhou, and McLoyd. We consider three questions raised in their comments. What does it mean to focus on Asian Americans? How should we examine development across the life course? How can we generate more policy- and practice-relevant research?. PMID- 27392802 TI - Erratum. PMID- 27392803 TI - Synergism of thymol, carvacrol and eugenol in larvae of the cattle tick, Rhipicephalus microplus, and brown dog tick, Rhipicephalus sanguineus. AB - The effects of combinations of the monoterpenes thymol and carvacrol and the phenylpropanoid eugenol in larvae of Rhipicephalus microplus (Canestrini, 1888) (Acari: Ixodidae) and Rhipicephalus sanguineus sensu lato (s.l.) (Acari: Ixodidae) were assessed by the larval packet test. The CompuSyn program was used to make qualitative assessments of the effects (synergistic, additive and antagonistic) of the associations. The effects of all combinations tested against R. microplus larvae were synergistic, with combination indices (CIs) <0.70. When tested against R. sanguineus, eight of the mixtures showed a synergistic effect (CI < 0.70); only the carvacrol + thymol mixture at LC50 presented a moderate synergistic effect, with CIs between 0.70-0.90. This study is the first to determine the effects of the interactions of these substances in the control of these two tick species. The combinations of carvacrol + thymol, carvacrol + eugenol and thymol + eugenol have synergistic effects in R. microplus and R. sanguineus s.l. larvae. PMID- 27392804 TI - Case-control study of neonatal group B streptococcal disease risk factors in a Dublin maternity hospital over a 13-year period. PMID- 27392805 TI - A community-based, mixed-methods study of the attitudes and behaviors of men regarding modern family planning in Nigeria. AB - OBJECTIVES: To investigate the knowledge, attitudes, and extent of involvement of men in family planning in Nigeria, and to evaluate spousal communication regarding family planning. METHODS: A community-based, mixed-methods study enrolled participants in Gwagwalada, Abuja, Nigeria between January 11 and June 30, 2012. Quantitative surveys including semi-structured interviews were used to collect information from married men regarding their knowledge and attitudes to modern family planning. The qualitative components constituted focus group discussion sessions and in-depth interviews that included married men, married women, religious leaders, community leaders, and family-planning providers. RESULTS: Quantitative surveys were completed by 152 men; 99 (65.1%) reported that they would accompany their wives to family-planning clinics in the future, 116 (76.3%) reported approving of the use of modern contraception by their wives, and 132 (86.8%) reported wanting to know more about family planning. Both quantitative and qualitative aspects of the study indicated that husbands were the major decision makers regarding family size, choice of contraceptive, and pregnancy timing. CONCLUSION: In terms of fertility goals and family planning, men were the primary decision makers; consequently, obtaining their support and commitment to family planning is of crucial importance in Nigeria. PMID- 27392806 TI - Age-stratified analysis of long-term outcomes of transvaginal mesh repair for treatment of pelvic organ prolapse. AB - OBJECTIVE: To investigate long-term outcomes after transvaginal mesh repair among patients with pelvic organ prolapse in different age groups. METHODS: A retrospective cohort study was conducted among women who underwent transvaginal mesh repair with polypropylene mesh for pelvic organ prolapse of stage II or higher between January 2007 and November 2011 at a center in Shanghai, China. Patients were invited to attend a follow-up appointment between July 2014 and May 2015. Surgical outcomes were compared among three age groups (<=59, 60-74, and >=75 years), and quality-of-life questionnaires were evaluated. Multivariate logistic regression was used to identify risk factors associated with recurrent prolapse and mesh exposure. RESULTS: Among 158 patients, 143 (90.5%) were objectively cured and 149 (94.3%) were subjectively cured at follow-up. Surgical outcomes were similar across all age groups. Significant improvements were observed on the Pelvic Floor Distress Inventory across all applicable subscales in all age groups (P<0.001 for all). Multivariate logistic regression showed that an active postoperative sex life significantly increased the risk of mesh exposure (odds ratio 11.89, 95% confidence interval 1.08-131.48; P=0.043). CONCLUSION: Transvaginal mesh repair was found to be a safe and effective technique for treating pelvic organ prolapse among women of all ages. An active postoperative sex life increased the odds of mesh exposure. PMID- 27392807 TI - Novel heterozygous mutation in ANO3 responsible for craniocervical dystonia. PMID- 27392808 TI - Upper gastrointestinal bleeding following transcatheter aortic valve replacement: A retrospective analysis. AB - OBJECTIVES: The aim of this study was to identify the incidence of upper gastrointestinal bleeding (UGIB) in the postprocedural period following transcatheter aortic valve replacement (TAVR). BACKGROUND: As TAVR moves into intermediate- and low-risk patients, it has become increasingly important to understand its extracardiac complications. The patient population undergoing TAVR have clinical and demographic characteristics that place them at significant risk of UGIB. Practical aspects of TAVR, including use of antithrombotic therapy, further increase risk of UGIB. METHODS: A retrospective single-center evaluation of 841 patients who underwent TAVR between January 2005 and August 2014 was performed in conjunction with analysis of referral patterns to the gastroenterology service for UGIB at the same site. RESULTS: The overall risk of UGIB following TAVR was found to be 2.0% (n = 17/841). Additionally, the risk of UGIB in patients receiving triple antithrombotic therapy was found to be 10-fold greater than patients not receiving triple antithrombotic therapy (11.8% vs 1.0%). Endoscopy findings demonstrated five high-risk esophageal lesions including erosive esophageal ulcers, visible vessels at the GE junction, erosions at distal esophagus, and an actively bleeding esophageal ring that had been intubated through by the transesophageal echocardiography (TEE) probe. CONCLUSIONS: This large cohort study demonstrates that TAVR is associated with a moderate risk of severe UGIB. The results of this study suggest that patients on triple antithrombotic therapy are at highest risk for severe UGIB. (c) 2016 Wiley Periodicals, Inc. PMID- 27392809 TI - Assessing the impact of minimizing arginine conversion in fully defined SILAC culture medium in human embryonic stem cells. AB - We present a fully defined culture system (adapted Essential8TM [E8TM ] medium in combination with vitronectin) for human embryonic stem cells that can be used for SILAC purposes. Although a complete incorporation of the labels was observed after 4 days in culture, over 90% of precursors showed at least 10% conversion. To reduce this arginine conversion, E8TM medium was modified by adding (1) l proline, (2) l-ornithine, (3) Nomega -hydroxy-nor-l-arginine acetate, or by (4) lowering the arginine concentration. Reduction of arginine conversion was best obtained by adding 5 mM l-ornithine, followed by 3.5 mM l-proline and by lowering the arginine concentration in the medium to 99.5 MUM. No major changes in pluripotency and cell amount could be observed for the adapted E8TM media with ornithine and proline. However, our subsequent ion mobility assisted data independent acquisition (high-definition MS) proteome analysis cautions for ongoing changes in the proteome when aiming at longer term suppression of arginine conversion. PMID- 27392811 TI - Decontamination of titanium implants using physical methods. AB - OBJECTIVES: Current decontamination methods of titanium (Ti) implant present limited success in achieving predictable re-osseointegration. We hypothesized that even though these techniques could be useful in elimination of bacteria, they might be unsuccessful in removing organic contaminants and restoring the original surface composition. The aim of this study was to assess the effect of four decontamination methods on the surface chemistry and bacterial load of biofilm-contaminated implant surfaces in order to improve implant surface decontamination. MATERIAL AND METHODS: The ability of clinically available methods such as metal and plastic curettes, Ti brushes and Er: YAG laser to decontaminate Ti implant surfaces was assessed. Surface morphology, chemical composition and properties of machined Ti discs (O 5.0 and 1.0 mm thick) were analysed before and after oral biofilm contamination using scanning electron microscope and X-ray photoelectron spectroscopy. The presence and viability of bacteria were evaluated with live-dead assays. RESULTS: Biofilm contamination created an organic layer rich in hydrocarbons and bacteria that covered entirely the Ti surfaces. This organic layer has tightly adhered to Ti surfaces and could not be completely removed with any of the methods assessed. Ti brushes achieved greater elimination of organic contaminants and bacteria than curettes and Er: YAG laser; however, none of them was able to restore the original surface chemistry. Alternatively, Er: YAG laser-treated surfaces showed the lowest live to-dead bacterial ratio. CONCLUSIONS: Ti brushes were more effective than curettes (metal or plastic) and Er: YAG laser in decontaminating Ti implant surfaces, although none of these techniques was able to completely eliminate surface contamination. Er: YAG laser was more effective than curettes and Ti brushes in killing the biofilm bacteria. PMID- 27392810 TI - Expression of heavy chain-only antibodies can support B-cell development in light chain knockout chickens. AB - Since the discovery of antibody-producing B cells in chickens six decades ago, chickens have been a model for B-cell development in gut-associated lymphoid tissue species. Here we describe targeting of the immunoglobulin light chain locus by homologous recombination in chicken primordial germ cells (PGCs) and generation of VJCL knockout chickens. In contrast to immunoglobulin heavy chain knockout chickens, which completely lack mature B cells, homozygous light chain knockout (IgL(-/-) ) chickens have a small population of B lineage cells that develop in the bursa and migrate to the periphery. This population of B cells expresses the immunoglobulin heavy chain molecule on the cell surface. Soluble heavy-chain-only IgM and IgY proteins of reduced molecular weight were detectable in plasma in 4-week-old IgL(-/-) chickens, and antigen-specific IgM and IgY heavy chain proteins were produced in response to immunization. Circulating heavy-chain only IgM showed a deletion of the CH1 domain of the constant region enabling the immunoglobulin heavy chain to be secreted in the absence of the light chain. Our data suggest that the heavy chain by itself is enough to support all the important steps in B-cell development in a gut-associated lymphoid tissue species. PMID- 27392812 TI - Adoption of transoral robotic surgery compared with other surgical modalities for treatment of oropharyngeal squamous cell carcinoma. AB - BACKGROUND AND OBJECTIVES: Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US. METHODS: Cases of T1-T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried. RESULTS: Of 3,071 patients who underwent primary surgical management for T1-T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs. T1: OR 0.75, CI 0.37-0.51, P < 0.0001; T3 vs. T1: O.R. 0.33, CI 0.28-0.38, P < 0.0001), treatment at an academic cancer center (O.R. 2.23, C.I. 1.29-3.88, P = 0.004) and treatment at a high volume hospital (34-155 cases vs. 1-4 cases: O.R. 9.07, C.I. 3.19-25.79, P < 0.0001) were associated with increased TORS approach. Significant geographic variation was observed, with high adoption in the Middle Atlantic. Positive margin rates were lower when TORS was performed at a high volume versus low volume hospital (8.2% vs. 16.7% respectively, P = 0.001). CONCLUSIONS: Tumor and non-tumor factors are associated with TORS adoption. This analysis suggests uneven diffusion of this technology in the treatment of OPSCC. J. Surg. Oncol. 2016;114:405-411. (c) 2016 Wiley Periodicals, Inc. PMID- 27392813 TI - Erratum. PMID- 27392814 TI - Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection. AB - Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 MUg mL-1 ) compared to posaconazole SUS (median 1.0 MUg mL-1 ). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST. PMID- 27392815 TI - Anastomosis to the common and proper digital vessels in free flap soft tissue reconstruction of the hand. AB - OBJECTIVE: This study seeks to demonstrate the safety of anastomosing free flaps to the common or proper digital artery, and to the volar or dorsal digital vein in soft tissue reconstruction of the hand; as well, as to discuss the advantages of this technique. METHODS: Retrospective review of all patients who underwent free flap reconstruction of the hand in two institutions over a period of 5 years. RESULTS: A total of 29 free flaps (9 great toe pulp, 7 anterolateral thigh, 6 second toe pulp, 4 radial artery perforator, 2 partial medial rectus, 1 lateral arm) in 28 patients met our inclusion criteria. All recipient vessels were the proper or common digital artery and the volar or dorsal digital vein. There was one case of venous congestion that resolved with leeching. There was no partial or total loss of any of the flaps. CONCLUSION: Anastomosing soft tissue free flaps to the common or proper digital artery, and the volar or dorsal digital vein is a safe and effective approach with numerous advantages that should be considered in the reconstruction of soft tissue defects of the hand. (c) 2016 Wiley Periodicals, Inc. Microsurgery, 38:21-25, 2018. PMID- 27392816 TI - Adaptive differentiation in floral traits in the presence of high gene flow in scarlet gilia (Ipomopsis aggregata). AB - Plant-pollinator interactions are thought to be major drivers of floral trait diversity. However, the relative importance of divergent pollinator-mediated selection vs. neutral processes in floral character evolution has rarely been explored. We tested for adaptive floral trait evolution by comparing differentiation at neutral genetic loci to differentiation at quantitative floral traits in a putative Ipomopsis aggregata hybrid zone. Typical I. aggregata subsp. candida displays slender white tubular flowers that are typical of flowers pollinated by hawkmoths, and subsp. collina displays robust red tubular flowers typical of flowers pollinated by hummingbirds; yet, hybrid flower morphs are abundant across the East Slope of the Colorado Rockies. We estimated genetic differentiation (FST ) for nuclear and chloroplast microsatellite loci and used a half-sib design to calculate quantitative trait divergence (QST ) from collection sites across the morphological hybrid zone. We found little evidence for population structure and estimated mean FST to be 0.032. QST values for several floral traits including corolla tube length and width, colour, and nectar volume were large and significantly greater than mean FST . We performed multivariate comparisons of neutral loci to genetic correlations within and between populations and found a strong signal for divergent selection, suggesting that specific combinations of floral display and reward traits may be the targets of selection. Our results show little support for historical subspecies categories, yet floral traits are more diverged than expected due to drift alone. Non-neutral divergence for multivariate quantitative traits suggests that selection by pollinators is maintaining a correlation between display and reward traits. PMID- 27392817 TI - Successful long-term outcome of liver transplantation in late-onset lysosomal acid lipase deficiency. AB - Late-onset LAL deficiency, previously referred to as cholesteryl ester storage disorder, is a rare lysosomal storage disorder characterized by accumulation of cholesteryl esters. It has a heterogeneous clinical phenotype including abdominal pain, poor growth, hyperlipidemia with vascular complications and hepatosplenomegaly. End-stage liver disease may occur, but there are few reports of successful LT. There are also concerns that systemic manifestations of the disease might persist post-LT. We report a case with excellent outcome eight yr following LT. The subject was noted to have asymptomatic hepatosplenomegaly during an intercurrent illness, and LAL deficiency was confirmed with compound heterozygosity in the LIPA. Despite dietary fat restriction, he developed signs of progressive liver disease and subsequently developed hepatopulmonary syndrome. He underwent cadaveric LT at the age of nine and a half yr and recovered with prompt resolution of hepatopulmonary syndrome. Eight yr post-transplant he has normal growth, normal lipid profile, and liver and renal function tests. Liver histology showed no evidence of disease recurrence at this stage. LT in this subject resulted in an excellent functional correction of late-onset LAL deficiency. PMID- 27392818 TI - Ss-Rhs1, a secretory Rhs repeat-containing protein, is required for the virulence of Sclerotinia sclerotiorum. AB - Sclerotinia sclerotiorum is a devastating necrotrophic plant pathogen with a worldwide distribution. Cell wall-degrading enzymes and oxalic acid are important to the virulence of this pathogen. Here, we report a novel secretory protein, Ss Rhs1, which is essential for the virulence of S. sclerotiorum. Ss-Rhs1 is believed to contain a typical signal peptide at the N-terminal and eight rearrangement hotspot (Rhs) repeats. Ss-Rhs1 exhibited a high level of expression at the initial stage of sclerotial development, as well as during the hyphal infection process. Targeted silencing of Ss-Rhs1 resulted in abnormal colony morphology and reduced virulence on host plants. Microscopic observations indicated that Ss-Rhs1-silenced strains exhibited reduced efficiency in compound appressoria formation. PMID- 27392820 TI - Protective effect of melatonin on the development of abdominal aortic aneurysm in a rat model. AB - BACKGROUND: Oxidative injury, inflammation, and apoptosis are involved in the progression of abdominal aortic aneurysm (AAA). Melatonin (MLT) has been reported with an effective antioxidant activity. The objective of the present study was to investigate whether MLT could suppress the development of AAA. METHODS: The AAA model was introduced by intraluminal perfusion of elastase in rats. All rats were divided into three groups as follows: (1) sham; (2) AAA + vehicle; and (3) AAA + MLT. Daily administration of MLT (10 mg/kg/d) or vehicle started 3 d before the perfusion and continued for 28 d after perfusion. An ultrasound system was applied to measure the dilation of the aorta. Histologic assays were performed to evaluate the structure, morphology, and apoptotic cells of the aortas; biochemical assays to determine the levels of proteins and lipid peroxide, activities of superoxide dismutase and NADPH oxidases, and cell viability; dihydroethidium fluorescence staining and flow cytometry to detect the presence of reactive oxygen species, and/or cell apoptosis; and electron microscopy to observe the ultrastructure of mitochondria. Cell lines A7R5 and RAW 264.7 were used for in vitro experiments. RESULTS: MLT treatment inhibited dilation of the aorta very likely through its antioxidant property; significantly reduced the levels of lipid peroxide, activities of NADPH oxidases, and content of reactive oxygen species; remarkably inhibited NF-kappaB signaling pathway and activities of matrix metalloproteinases triggered by elastase perfusion. As a result, the mitochondrion-dependent apoptosis was suppressed, cellular energy (ATP) supply was recovered, and mitochondrial morphology remained intact. CONCLUSIONS: Our results demonstrate the beneficial effects of MLT on inhibition of AAA formation, suggesting that MLT could be a potential agent for prevention of the development of human AAA. PMID- 27392819 TI - Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces. AB - KEY POINTS: The gastrointestinal epithelial enterochromaffin (EC) cell synthesizes the vast majority of the body's serotonin. As a specialized mechanosensor, the EC cell releases this serotonin in response to mechanical forces. However, the molecular mechanism of EC cell mechanotransduction is unknown. In the present study, we show, for the first time, that the mechanosensitive ion channel Piezo2 is specifically expressed by the human and mouse EC cells. Activation of Piezo2 by mechanical forces results in a characteristic ionic current, the release of serotonin and stimulation of gastrointestinal secretion. Piezo2 inhibition by drugs or molecular knockdown decreases mechanosensitive currents, serotonin release and downstream physiological effects. The results of the present study suggest that the mechanosensitive ion channel Piezo2 is specifically expressed by the EC cells of the human and mouse small bowel and that it is important for EC cell mechanotransduction. ABSTRACT: The enterochromaffin (EC) cell in the gastrointestinal (GI) epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine; 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The present study aimed to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of the small bowel. Piezo2 immunoreactivity localized specifically within EC cells of human and mouse small bowel epithelium. The EC cell model released 5-HT in response to stretch, and had Piezo2 mRNA and protein, as well as a mechanically-sensitive inward non-selective cation current characteristic of Piezo2. Both inward currents and 5-HT release were inhibited by Piezo2 small interfering RNA and antagonists (Gd3+ and D-GsMTx4). Jejunum mucosal pressure increased 5-HT release and short-circuit current via submucosal 5-HT3 and 5-HT4 receptors. Pressure-induced secretion was inhibited by the mechanosensitive ion channel antagonists gadolinium, ruthenium red and D-GsMTx4. We conclude that the EC cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5-HT release and an increase in mucosal secretion. Therefore, Piezo2 is critical to EC cell mechanosensitivity and downstream physiological effects. PMID- 27392822 TI - Superior Red Blood Cell Generation from Human Pluripotent Stem Cells Through a Novel Microcarrier-Based Embryoid Body Platform. AB - In vitro generation of red blood cells (RBCs) from human embryonic stem cells and human induced pluripotent stem cells appears to be a promising alternate approach to circumvent shortages in donor-derived blood supplies for clinical applications. Conventional methods for hematopoietic differentiation of human pluripotent stem cells (hPSC) rely on embryoid body (EB) formation and/or coculture with xenogeneic cell lines. However, most current methods for hPSC expansion and EB formation are not amenable for scale-up to levels required for large-scale RBC generation. Moreover, differentiation methods that rely on xenogenic cell lines would face obstacles for future clinical translation. In this study, we report the development of a serum-free and chemically defined microcarrier-based suspension culture platform for scalable hPSC expansion and EB formation. Improved survival and better quality EBs generated with the microcarrier-based method resulted in significantly improved mesoderm induction and, when combined with hematopoietic differentiation, resulted in at least a 6 fold improvement in hematopoietic precursor expansion, potentially culminating in a 80-fold improvement in the yield of RBC generation compared to a conventional EB-based differentiation method. In addition, we report efficient terminal maturation and generation of mature enucleated RBCs using a coculture system that comprised primary human mesenchymal stromal cells. The microcarrier-based platform could prove to be an appealing strategy for future scale-up of hPSC culture, EB generation, and large-scale generation of RBCs under defined and xeno free conditions. PMID- 27392821 TI - Smoking status and symptom burden in surgical head and neck cancer patients. AB - OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) patients who smoke are at risk for poor treatment outcomes. This study evaluated symptom burden and clinical, sociodemographic, and psychosocial factors associated with smoking in surgical patients to identify potential targets for supportive care services. STUDY DESIGN: Cross-sectional survey. METHODS: Individuals with HNSCC of the oral cavity, larynx, or pharynx were recruited from two cancer centers and completed questionnaires assessing smoking status (never, former, current/recent), patient characteristics, and symptoms before surgery. RESULTS: Of the 103 patients enrolled, 73% were male, 52% were stage IV, 41% reported current/recent smoking, and 37% reported former smoking. Current/recent smokers were less likely than former smokers to have adequate finances (53% vs. 89%, P = .001) and be married/partnered (55% vs. 79%, P = .03). Current/recent smokers were also more likely than both former and never smokers to be unemployed (49% vs. 40% and 13%, respectively, all P = .02) and lack health insurance (17% vs. 5% and 13%, respectively, all P <=.04). Fatalistic beliefs (P = .03) and lower religiosity (P =.04) were more common in current/recent than never smokers. In models adjusted for sociodemographic/clinical factors, current/recent smokers reported more problems than former and never smokers with swallowing, speech, and cough (P <=.04). Current/recent smokers also reported more problems than never smokers with social contact, feeling ill, and weight loss (P <= .02). CONCLUSIONS: HNSCC patients reporting current/recent smoking before surgery have high-risk clinical and sociodemographic features that may predispose them to poor postoperative outcomes. Unique symptoms in HNSCC smokers may be useful targets for patient-centered clinical monitoring and intervention. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:127-133, 2017. PMID- 27392823 TI - [Not Available]. AB - In order to evaluate the attractiveness of France for conducting international clinical trials, a survey is performed every two years among pharmaceutical companies that are based in France or have affiliates in France. Initiated in 2006, the current survey was much more representative than the previous ones with 20 companies accounting for 61% of the French market. This survey included 352 international phase II and III clinical studies carried out in 2004 and 2005, 74 countries, 17 345 centres and 137 989 patients. France has participated to half of the overall number of international clinical trials. France ranked among the best European recruiters (0,19 patient/1000 inhabitants) at the second position behind Scandinavian countries, taking in account numbers of inhabitants. Protocols are now to be given the go-ahead by Ethics Committee (CCPPRB) within 60 days. With a high productivity in phase IIb and in oncology, France is still an attractive place to locate clinical research. PMID- 27392824 TI - [Not Available]. AB - The global extracts of Nepeta atlantica Ball and Nepeta tuberosa L. ssp. reticulata (Desf.) Maire are especially rich in secondary metabolites of the type irido'id lactonique and glucosidique and of type lupane triterpine. The aerial part of each species is crushed, and then extracted by cold maceration in methanol. These total extracts are in the form of suspension in Arabic gum with 5%. they are tested on the mice for the tests of acute toxicity like for the peripheral analgesic activity according to the test of Koster; and also on the rats for the central analgesic activity of the morphine type based on the test "Tail Flick". The acute toxicity evaluation of these extracts follows upon the determination of the lethal amounts 50% of essential oils from these two species, already given it is specified here by the lethal dose 50% (DL50) of 1672+/-232 mg/kg with confidence limits [1030 - 2320] mg/kg for Nepeta atlantica and 1401 +/ 97.29 mg/kg with confidence limits [1130 - 1670] mg/kg for Nepeta tuberosa L. ssp. reticulata. The tests of Koster in the mouse and the "Tail Flik" in the rat showed that the global extracts of the studied species have all two greatly peripheral analgesic activity with an important protection against abdominal cramp 67.91% and 75.53% for 60 mg/kg IP respectively for Nepeta atlantica and Nepeta tuberosa L. ssp. Reticulata, which rise up to 90.10% and 92.89% for 120 mg/kg IP. A central morphine like analgesic activity is record with 120 mg/kg IP for the two species. PMID- 27392826 TI - First Appearance of HIV-1 CRF07_BC and CRF08_BC Outside China. AB - Neither full length genomic sequence of CRF07_BC nor that of CRF08_BC was found in any other countries since they originated in Yunnan, China, in early 1990s. Here, we first report that CRF07_BC and CRF08_BC appeared among intravenous drug users in Shan state of Myanmar bordering Yunnan, and confirmed that they spread from China to Myanmar. The introduction of CRF07_BC and CRF08_BC in northern Myanmar may forebode a changing subtype epidemic in Southeast Asia. PMID- 27392827 TI - Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force. PMID- 27392828 TI - A two-step filtering-based iterative image reconstruction method for interior tomography. AB - The optimization-based method that utilizes the additional sparse prior of region of-interest (ROI) image, such as total variation, has been the subject of considerable research in problems of interior tomography reconstruction. One challenge for optimization-based iterative ROI image reconstruction is to build the relationship between ROI image and truncated projection data. When the reconstruction support region is smaller than the original object, an unsuitable representation of data fidelity may lead to bright truncation artifacts in the boundary region of field of view. In this work, we aim to develop an iterative reconstruction method to suppress the truncation artifacts and improve the image quality for direct ROI image reconstruction. A novel reconstruction approach is proposed based on an optimization problem involving a two-step filtering-based data fidelity. Data filtering is achieved in two steps: the first takes the derivative of projection data; in the second step, Hilbert filtering is applied in the differentiated data. Numerical simulations and real data reconstructions have been conducted to validate the new reconstruction method. Both qualitative and quantitative results indicate that, as theoretically expected, the proposed method brings reasonable performance in suppressing truncation artifacts and preserving detailed features. The presented local reconstruction method based on the two-step filtering strategy provides a simple and efficient approach for the iterative reconstruction from truncated projections. PMID- 27392829 TI - Diagnosis value of multi-slice spiral CT in renal trauma. AB - Computed tomography (CT) is most commonly used as a noninvasive approach in diagnosis of internal organ injures. Use of multi-slice spiral CT becomes more popular in diagnosis of trauma because of its ability to generate 3D volumetric information. This study evaluated the diagnostic value of multi-slice spiral computed tomography (MSCT) with enhanced scanning in renal trauma. In total, 126 patients with kidney injury underwent MSCT scanning from a single hospital in the southern of China between January 2012 and February 2016. According to kidney injury grading standards of American Association for the Surgery of Trauma (AAST), 30 were diagnosed and classified in level I, 26 in level II, 42 in level III, 17 in level IV, 11 in level V. The outcomes of MSCT enhanced scanning achieve a 100% diagnostic accuracy rate, which was confirmed by surgical findings. We concluded that the enhanced MSCT scan permits reliable detection of renal trauma and the associated organ or tissue injuries, providing important clinical value for the diagnosis and classification of renal trauma or internal organ injures. PMID- 27392830 TI - Integrated Nationwide Electronic Health Records system: Semi-distributed architecture approach. AB - BACKGROUND: The integration of heterogeneous electronic health records systems by building an interoperable nationwide electronic health record system provides undisputable benefits in health care, like superior health information quality, medical errors prevention and cost saving. OBJECTIVE: This paper proposes a semi distributed system architecture approach for an integrated national electronic health record system incorporating the advantages of the two dominant approaches, the centralized architecture and the distributed architecture. METHODS: The high level design of the main elements for the proposed architecture is provided along with diagrams of execution and operation and data synchronization architecture for the proposed solution. RESULTS: The proposed approach effectively handles issues related to redundancy, consistency, security, privacy, availability, load balancing, maintainability, complexity and interoperability of citizen's health data. CONCLUSIONS: The proposed semi-distributed architecture offers a robust interoperability framework without healthcare providers to change their local EHR systems. It is a pragmatic approach taking into account the characteristics of the Greek national healthcare system along with the national public administration data communication network infrastructure, for achieving EHR integration with acceptable implementation cost. PMID- 27392832 TI - Applying the results of Health Technology Assessment reports in developing countries, the pale face of coin. PMID- 27392831 TI - Validity of a Wireless Gait Analysis Tool (Wi-GAT) in assessing spatio-temporal gait parameters at slow, preferred and fast walking speeds. AB - BACKGROUND: The wireless gait assessment tool (Wi-GAT) measures have been shown to have good to excellent concurrent validity with preferred walking speeds, however, the validity of the Wi-GAT measures at slow and fast walking speeds is unknown. OBJECTIVE: To establish validity of the Wi-GAT spatio-temporal gait measures at slow, fast, and preferred walking speeds. METHODS: Twenty two healthy adult volunteers, with a mean age of 25.7 (+/- 5.3) participated in this study. The spatio-temporal gait variables of each participant were concurrently recorded using the GAITrite and the Wi-GAT system, while the participants performed 3 trials for each walking speed in a randomized order. Intraclass correlation analyses were performed to establish the agreement between the measures recorded by the GAITrite and Wi-GAT systems. RESULTS: Walking speed measured both by the Wi-GAT and the GAITrite systems showed excellent agreement for preferred (ICC = 0.979 p< 0.001), slow (ICC = 0.989 p< 0.001) and fast (ICC = 0.967 p< 0.001) walking speeds. Most gait parameters recorded at slow walking speed showed good (ICC > 0.70) to excellent (ICC > 0.85) agreement. CONCLUSIONS: Gait parameters recorded by the Wi-GAT system showed fair to excellent validity for preferred and slow walking speeds. PMID- 27392834 TI - The repeatability of oVEMP in response to low-frequency vibration against the vertex and forehead. AB - BACKGROUND: The measurement of ocular Vestibular Evoked Myogenic Potentials (oVEMP) is a novel method for investigating vestibular function. Stimulus and recording techniques vary in the literature. A standardized test procedure is desirable in order to ensure repeatable results. OBJECTIVE: To investigate the magnitude and repeatability of the asymmetry ratio (AR) of oVEMPs in response to low-frequency bone conducted vibration (BCV) applied to the forehead and vertex in a healthy population. METHODS: 20 healthy subjects were tested three times by stimulating with 125 Hz BCV at the forehead and the vertex. The first two tests were performed with the subject remaining in the examining room and the electrodes in place. After a short break, a third test was performed with a new set of electrodes. The AR was calculated for each test based on the evoked oVEMPs responses from the left and the right side. The AR magnitude, variance and repeatability coefficients were evaluated to determine which of the two stimulus sites is best suited in clinical use. RESULTS: Stimulation at the forehead resulted in a statistically significant lower median AR compared to the vertex. The forehead had lower repeatability coefficients, and statistically significantly lower variances. CONCLUSIONS: This study indicates that the forehead is a better stimulation site than the vertex for low-frequency BCV in clinical use. PMID- 27392833 TI - The development of the ICF vestibular environmental scale. AB - People with vestibular disorders report changes in symptoms based on their environment with many situations increasing their symptoms. The purpose of this paper was to utilize the International Classification of Functioning Disability and Health (ICF) from the World Health Organization (WHO) to describe common environmental triggers for dizziness in persons living with balance and vestibular disorders. A multi-centre cross-sectional study was conducted with four different centres on three different continents, including patients from the United States (Pittsburgh), Germany (Munich), Jordan (Amman) and Saudi Arabia (Riyadh). SUBJECTS: Three hundred eighty one persons with vestibular disorders participated. METHODS: A 9-item questionnaire (the Vestibular Environmental Scale) was developed from existing ICF items, which were compared to Dizziness Handicap Inventory (DHI) scores. Sixty-five percent of participants reported that "quick movements in the vicinity" increased symptoms, "crowds" at 45%, and "design of buildings, e.g. narrow hallways, stairs, elevators" at 42%. The "crowds" item was a good positive predictor of psychogenic vertigo (OR 1.8, 95% Confidence Interval 1.03-3.16), while "food" (OR 0.47, 95% Confidence Interval 0.17-1.29) and "light" (OR 0.41 95% Confidence Interval 0.23-0.75) were negative predictors of psychogenic vertigo. There also was a positive correlation between the number of triggers and DHI score (Spearman correlation coefficient 0.47, p < 0.0001). Sixty-eight percent of the subjects reported an increase in symptoms with between 1 and 4 environmental triggers. In our cross cultural sample, environmental triggers affect dizziness in persons living with balance and vestibular disorders. The use of items from the ICF of the WHO may help to promote cross cultural sharing of information in persons with dizziness. PMID- 27392835 TI - About the pathophysiology of acute unilateral vestibular deficit - vestibular neuritis (VN) or peripheral vestibulopathy (PVP)? AB - OBJECTIVE: To determine whether patients with acute unilateral peripheral vestibulopathy (PVP), often called "vestibular neuritis/neuronitis or neuropathy" (VN) have a vestibular lesion pattern consistent with the distribution of the neurological afferents. BACKGROUND: Much is known about the clinical nature of PVP, however less so about its etiology and pathogenesis. Due to the frequency with which VN is used to describe the syndrome, an inflammation of the vestibular nerve or of one of its branches is often assumed to be the cause of PVP, though there is insufficient data so far to support this assumption. METHODS: We conducted a retrospective study of 25 patients who had presented to our clinic with PVP and had all vestibular receptor organs tested shortly after start of symptoms. We analysed their vestibular lesion patterns in order to determine whether they were consistent with the neuritis hypothesis (NH). RESULTS: The lesion patterns varied conspicuously. 76% did not follow an innervation pattern, thereby contradicting the NH and only 24% had a lesion pattern that either definitely (16%) or probably (8%) supported the NH. CONCLUSION: These results should remind us to be careful before jumping to quick conclusions about the pathogenetic nature of PVP. With any reason to question VN as the only cause of PVP, we should reconsider the treatment approach to PVP. If the cause probably or even possibly lies inside the vestibular labyrinth, an intratympanic steroid injection might prove to be a more effective measure, even in first-line treatment. If the etiology is unsure, a combination of systemic and intratympanic steroid treatment may be adequate. PMID- 27392836 TI - Posturographic profile of patients with persistent postural-perceptual dizziness on the sensory organization test. AB - BACKGROUND/OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) was defined by expert consensus for the forthcoming International Classification of Diseases, 11th edition. Its diagnostic criteria were derived from phobic postural vertigo and chronic subjective dizziness. Two key symptoms are postural unsteadiness and visually induced dizziness. We observed that patients with PPPD tended to perform poorly on multiple conditions of the EquiTest(r) Sensory Organization Test (SOT) and sought to investigate this phenomenon systematically. METHODS: We examined cross-sectional, pair-wise group differences in mean scores from SOT conditions 1 6 and composite scores among 20 patients with PPPD, 15 patients recovered from acute vestibular syndromes, and 15 normal individuals (all female, 43 +/- 9 years old). We also compared proportions of patients in each group with abnormal sensory analyses, and poor performance across multiple conditions. RESULTS: Patients with PPPD had significantly lower mean scores than normal individuals on conditions 2-6 and the composite, and lower than recovered patients on conditions 2-3. Recovered patients had significantly lower mean scores than normal individuals on conditions 4-6 and the composite. Patients with PPPD had the greatest likelihood of abnormal sensory analyses. CONCLUSIONS: Patients with PPPD had difficulties with postural control across multiple sensory challenges, consistent with postulated neurophysiologic mechanisms of this condition. PMID- 27392837 TI - Vestibulo-ocular reflex dynamics with head-impulses discriminates spinocerebellar ataxias types 1, 2 and 3 and Friedreich ataxia. AB - OBJECTIVE: Although the diagnosis of inherited ataxias is ultimately genetic, this usually means an extensive and expensive process. This justifies the search for distinct clinical signs that may potentially help orient molecular diagnosis. METHODS: We explored the vestibulo-ocular reflex (VOR) with the video Head Impulse Test in patients diagnosed with spinocerebellar ataxia (SCA) type 3 (n = 15), type 1 (n = 4) and type 2 (n = 4), Friedreich's ataxia (FA) (n = 9) and healthy controls (n = 40). We estimated the latency, regression (VORr) and instantaneous VOR gain at 40, 60 and 80 ms (VOR40, VOR60 and VOR80), and determined the latency, peak-velocity and occurrence rate of catch-up saccades triggered with head-impulses. RESULTS: VOR latency was higher in FA (p < 0.001) and SCA3 (p = 0.02) as compared to controls, discriminating FA from other ataxic patients with an overall diagnostic accuracy of 88%. VORr, VOR40 and VOR60 were significantly lower in FA and SCA3 (p < 0.01). VOR80 was only significantly lower than controls in SCA3 (p < 0.01), discriminating these from other ataxic patients with an overall diagnostic accuracy of 78%. Covert saccades were only triggered in SCA3 but with low occurrence rate and peak velocity (11.1 +/- 28.5% and 77.50 +/- 15.30 degrees /s) whereas overt saccades were present in all groups. VORr gain showed a negative correlation with disease severity evaluated with SARA (Spearman r = -0.46, p = 0.01). CONCLUSIONS: vHIT provides phenotypic information that differentiates these autosomal ataxias and can serve as a strategy to orient genetic diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity. PMID- 27392838 TI - Psychiatric comorbidities and use of milnacipran in patients with chronic dizziness. AB - BACKGROUND: Psychiatric comorbidities are an important issue in the treatment of chronic dizziness patients. OBJECTIVE: To test the correlation between psychiatric status and subjective handicaps and to examine the effects of milnacipran on handicaps. METHODS: Hospital anxiety and depression scale (HADS) and handicaps were assessed by a questionnaire before and eight weeks after milnacipran treatment (50 mg/day) in 29 consecutive patients with chronic dizziness. Effects of milnaciplan were compared with fluvoxamine (200 mg/day). RESULTS: A significant correlation was found between anxious and depressive scale scores and also between HADS and handicaps. Duration of symptoms was longer in the anxious/depressive group (HADS?13) than in the non-anxious/depressive group. Handicaps and HADS were significantly decreased after treatment only in the anxious/depressive group. There were no overall differences in drug effects between milnaciplan and fluvoxamine. However, the rate of patients with a post/pre ratio of handicaps <80% was higher in milnaciplan group compared with the fluvoxamine group. CONCLUSIONS: Not only anxiety disorders but also depression should be considered as comorbid psychiatric disorders in patients with chronic dizziness. Dizzy patients with psychiatric comorbidities have a longer duration of symptoms and more handicaps than those without psychiatric disorders. Milnacipran may be chosen as a treatment for patients with chronic dizziness with comorbid psychiatric disorders in case of and insufficient response to SSRIs. PMID- 27392839 TI - Posture variation in a car within the restrictions of the driving task. AB - BACKGROUND: Passive posture variation in vehicles could enable variation in pressure distribution and muscle activity to counter physical fatigue from static seating resulting in more comfort. The difference in posture, however, should not lead to perceived discomfort and aspects of driving should be considered such as operating the steering wheel, pedals and vision in the mirrors. OBJECTIVE: This study sets out to find out how much postural variation occurs during the driving task and how sensitive is the human body to these changes. METHODS: The first experiment was user evaluation and assessed how and when the changes in seat configuration were noticeable to the human body. The second experiment evaluated the influence of varying inclination of the backrest and the seat pan by the rating of typical aspects of driving. RESULTS: The differences in seat configuration during experiment 1, were so small that there was no consistency in the ratings for the same configuration. The most critical feature that restrains the posture is the location of the rear view mirror. CONCLUSIONS: The range-of motion is defined as -1 degrees to +1 degrees for the seat pan and 0 degrees to +1.5 degrees for the backrest based on the results of experiment 2 because of the restraints of the driving task. PMID- 27392840 TI - Intra and interrater reliability of spinal sagittal curves and mobility using pocket goniometer IncliMed(r) in healthy subjects. AB - BACKGROUND: Radiographic examination is the gold standard to evaluate spine curves, but ionising radiations limit routine use. Non-invasive methods, such as skin-surface goniometer (IncliMed(r)) should be used instead. OBJECTIVE: To evaluate intra- and interrater reliability to assess sagittal curves and mobility of the spine with IncliMed(r). METHODS: a reliability study on agonistic football players. Thoracic kyphosis, lumbar lordosis and mobility of the spine were assessed by IncliMed(r). Measurements were repeated twice by each examiner during the same session with between-rater blinding. Intrarater and interrater reliability were measured by Intraclass Correlation Coefficient (ICC), 95% Confidence Interval (CI 95%) and Standard Error of Measurement (SEM). RESULTS: Thirty-four healthy female football players (19.17 +/- 4.52 years) were enrolled. Statistical results showed high intrarater (0.805-0.923) and interrater (0.701 0.886) reliability (ICC > 0.8). The obtained intra- and interrater SEM were low, with overall absolute intrarater values between 1.39 degrees and 2.76 degrees and overall interrater values between 1.71 degrees and 4.25 degrees . CONCLUSIONS: IncliMed(r) provides high intra- and interrater reliability in healthy subjects, with limited Standard Error of Measurement. These results encourage its use in clinical practice and scientific research. PMID- 27392841 TI - The influence of different non-articular proximal forearm orthoses (brace) widths in the wrist extensors muscle activity, range of motion and grip strength in healthy volunteers. AB - PURPOSE: The purpose this study was perform a biomechanical evaluation to compare the influence of commercial models of different non-articular proximal forearm orthoses widths (2.5 cm, 5.5 cm, 7.5 cm and 12.0 cm) in the extensor muscle activation, range of motion and grip strength in healthy subjects. METHODS: Was analyzed data from extensor carpi radialis, extensor carpi ulnares and extensor digitorum comunis using surface electromyography, simultaneous with a wrist electrogoniometer MiotecTM and a hydraulic dynamometer JamarTM. The sequence of tests with all the commercial orthoses models was randomized. Statistics analyses were performed by linear model with mixed effects. RESULTS: According to our findings the non-articular proximal forearm orthoses (2.5 cm - narrowest) positioned close to lateral epicondyle provided lesser muscle activation on extensor carpi radialis brevis/longus and extensor digitorum comunis, decreased wrist extension and grip strength during submaximal grip task (p< 0.01). CONCLUSIONS: A narrow non-articular proximal forearm orthosis positioned close to the lateral epicondyle might decrease the extensor muscle activation and therefore could reduce mechanical stress on its insertion, based on this sample. Clinical studies must be conducted to confirm these findings. PMID- 27392842 TI - Synthetic meshes in the treatment of postoperative fascial dehiscence of the spine. AB - BACKGROUND: A fascial dehiscence after spinal instrumentation is usually located at the mechanically stressed interscapular thoracic spine and often causes cosmetic impairment and pain. However, therapy options remain barely discussed. Synthetic meshes have been successfully used in the treatment of abdominal hernias. OBJECTIVE: It was hypothesized that synthetic meshes are a successful treatment option for spinal fascial dehiscence. METHODS: This retrospective study of a prospective database investigated all consecutive patients who received a synthetic mesh for a fascial dehiscence of the spine between 2010 and 2014 after prior spinal instrumentation. Primary outcomes were healing of the fascial dehiscence, recurrence, infection, revision, subjective satisfaction on a visual analog scale (VAS), and the Oswestry Disability Index (ODI). Among others, secondary outcomes consisted of seroma formation and return to work. The evaluated risk factors consisted of the body mass index (BMI), outer abdominal fat (OAF), back tissue, smoking, immunomodulatory therapy, preoperative radiation dose, and instrumented levels. RESULTS: Sixteen patients with a mean follow up of 24 months were included. Every fascial dehiscence successfully healed with the synthetic mesh and there were no recurrences, infections or revisions. The mean subjective satisfaction level was VAS 7.3 and the mean ODI was 26%. Five (31%) patients had a seroma postoperatively, but did not show any differences in the outcome (e.g. ODI of 28%). In the patient group < 65 years (n = 12), all but two patients, who had work restrictions due to other diseases, regained at least some capacity to work. Worse ODI scores were found for patients with increased BMI, OAF, back tissue, cortisone therapy, instrumented levels, preoperative radiation dose, and for smokers. CONCLUSION: Synthetic meshes are a successful treatment option for spinal fascial dehiscence, even seemingly in patients with a higher risk profile such as obese and immunocompromised patients as well as in revision procedures. They are associated with respectable cosmetic results, pain relief and clinical outcome. Postoperatively, it is recommended to leave drains for more than five to seven days in order to avoid seroma formation and to avoid weight training for six weeks. Further prospective, comparative studies are recommended. PMID- 27392843 TI - Impairments of postural stability, core endurance, fall index and functional mobility skills in patients with patello femoral pain syndrome. AB - BACKGROUND: Postural control allows performance of daily and sports activities. The previous studies show that postural sway inceases in orthopaedic injuries such as osteoarthritis and total knee arthroplasty. OBJECTIVE: To compare postural sway, risk of falling and function between individuals with and without patellofemoral pain syndrome (PFS). METHODS: This study included 22 subjects with patellofemoral pain syndrome, age-matched pain-free 22 females serving as a control group. Visual anolog scale and Kujala were used to evaluate the pain. Posturographic assesment was performed by Tetrax posturographic device. Biering Modified Sorenson test for extensor endurance and sit-up test for flexor endurance were used for the evaluation of trunk endurance. Timed get-up and go test was used for lower extremity function. The Student's t Test was used to compare variables between the groups. The Pearson correlation coefficients were calculated to examine correlation between the quantitative variables. RESULTS: Postural sway included eyes open without pillow, eyes open on pillow, eyes closed on pillow, risk of falling, function and postural stabilization included flexor endurance, extansor endurance are impared in patient with patellofemoral pain syndrome when compare to controls. In subjects with PFPS increased postural sway significantly associated with body mass index (r= 0.52), pain duration (r= 0.43), postural control (extansor endurance) (r= -0.50) and risk of falling (r= 0.62) on pillow with open eyes. In addition we found function significantly related with postural control (extansor endurance and flexor endurance) (r= -0.59 and r= 0.59) and risk of falling (r= 0.77)CONCLUSIONS: Decreased neuromuscular control of the trunk core and increased postural sway and falling risk were found in patients with PFPS. Patients may be evaluated for deficits in postural control and falling risk before treatment. PMID- 27392844 TI - Serum levels of neuron-specific enolase in patients with fibromyalgia syndrome: Correlation with cognitive functions, quality of life and psychological state. AB - BACKGROUND: Fibromyalgia syndrome (FMS) is a non-articular rheumatic disorder of unclear etiology, characterized by widespread body pain, fatigue and, psychological complaintsOBJECTIVES: To investigate the serum levels of neuron specific enolase (NSE) in patients with FMS and to evaluate the relationship between cognitive function, quality of life and psychological state. MATERIALS AND METHODS: Fifty-five female patients diagnosed with fibromyalgia according to the American College of Rheumatology (ACR) classification criteria, and 40 healthy female subjects were enrolled in the study. Life quality scale [(Fibromyalgia Impact Questionnaire (FIQ)], psychological state (Beck Depression Scale), and cognitive dysfunction (mini mental test, clock drawing test) scales were used for patients and control subjects. Serum NSE levels were studied using the ECLIA method. RESULTS: No significant differences were found in the serum NSE levels between the FMS patients and the control subjects (p> 0.05). Life quality and psychological state scores were found to be higher in FMS patients relative to the control group (p< 0.001). However, no significant differences were detected in cognitive function (p> 0.05). Significant correlations were not found between the serum NSE levels and quality of life, psychological state and cognitive functions (p> 0.05). CONCLUSION: No significant difference was determined between the groups in terms of NSE levels. Further studies, including larger series, should be carried out to clarify this relationship. PMID- 27392845 TI - The presence and influence of posterior capsule tightness on different shoulder problems. AB - BACKGROUND: In the literature it has been shown that posterior capsule flexibility is a precursor to shoulder problems. However, no study thus far has shown the influence of the flexibility of posterior capsule in different shoulder pathologies. OBJECTIVE: This study set about to compare the role of posterior capsule tightness in different shoulder problems. METHODS: One-hundred-twenty five patients diagnosed with shoulder subacromial impingement syndrome (n= 52), partial rotator cuff tear (n= 31) or frozen shoulder (n= 42) and 30 asymptomatic peers participated in the study. Horizontal adduction was assessed in side-lying position for posterior capsule tightness. Pain was measured via the visual analogue scale and shoulder range of motion and active total elevation was assessed with goniometer. Hand behind the back (HBB) test was assessed the active internal rotation by measuring the distance between T5 and the thumb. RESULTS: It was found that the affected side of the posterior capsules of the patients with subacromial impingement syndrome (p< 0.001), partial rotator cuff tear (p< 0.001) and frozen shoulder (p< 0.001) was stiffer than their healthy side. There were significant differences among groups in the level of tightness in the posterior capsule between the affected and the healthy sides (p< 0.001). All range of motion of the shoulder including HBB test and the posterior capsule tightness of the affected side are found to be correlated (p< 0.05). CONCLUSIONS: This study emphasized that the posterior capsule's susceptibility to tightness is most evident in frozen shoulder among different shoulder problems. PMID- 27392846 TI - The importance of early rehabilitation in proximal humeral fracture: A clinical trial of efficacy and safety of a new endomedullary nail. AB - BACKGROUND: The aim of the surgical treatment in proximal humeral fractures is to maintain bone alignment facilitating an early shoulder mobilization. This can be obtained with the use of an endomedullary nail with specific characteristics: a proximal angular multiplanar stability and the possibility to place proximal screws in the calcar region. The objective of this randomized controlled trial is to investigate the effects of an early rehabilitation program in 3-part proximal humeral fractures treated with endomedullary nailing. MATERIALS AND METHODS: 126 patients treated with the Diphos Proximal Humeral Nail (PHN), followed with an Intensive Rehabilitation Program (IRP) started in the second postoperative day, were compared to 62 patients with a Standard Rehabilitation Program (SRP) where shoulder mobilization started after 3 weeks. The age of patients was under 65 years. Main Outcome measures were improvement of shoulder function based on Constant Score and quality of life on DASH questionnaire at 1, 3, 6 and 12 months after surgery. Safety outcome was no loss of radiological reduction at any follow up control. RESULTS: A difference considered statistically significant (95% confidence interval) was demonstrated by Constant scores at 3 and 6 months and by DASH questionnaire scores at 1 month after surgery between IRP and SRP groups, however without loss of radiological reduction and maintaining the full fracture healing at the same mean period of 1,8 +/- 0,7 months. DISCUSSION: This experience allows to highlight essential features of this new kind of endomedullary humeral nail, by its mechanical properties, in proximal humeral fractures in order to permit an early rehabilitation without creating displaced or consolidation delay. LEVEL OF EVIDENCE: III, randomized clinical-case-control study. PMID- 27392847 TI - The importance of trunk perception during brace treatment in moderate juvenile idiopathic scoliosis: What is the impact on self-image? AB - BACKGROUND: The perception of body image and the deformity of the trunk in patients with adolescent idiopathic scoliosis (AIS) are a silver lining that has yet to be discussed in the relevant literature during brace rehabilitation treatment. OBJECTIVE: To determine whether and how the use of the brace changes perception of the trunk in patients with AIS by the drawing test. METHODS: We observed 32 subjects with AIS from our Rehabilitation outpatient clinic and divided them into the brace treatment (BG-16 subjects) and the non-brace treatment (CG-16 subjects). Trunk perception and quality of life were evaluated using the Trunk Appearance Perception Scale and Scoliosis Research Society-22 questionnaire, and the perception of one's back was measured by the drawing test. RESULTS: Pain was lower in BG versus CG (p= 0.095). Satisfaction with the treatment was higher in BG than in CG (p= 0.002). Self-image did not differ significantly between the groups in terms of TAPS. Drawings of the most severe cases of scoliosis were made by the group without the brace. CONCLUSIONS: The use of the brace corrects the function of the trunk and has a positive influence on its perception. PMID- 27392848 TI - Case series of ultrasound-guided platelet-rich plasma injections for sacroiliac joint dysfunction. AB - BACKGROUND: Two-thirds of adults worldwide will experience low back pain at some point in their life. In the following case series, we present four patients with sacroiliac (SI) joint instability and severe chronic low back pain, which was refractory to other treatment modalities. OBJECTIVE: We investigated the efficacy of platelet-rich plasma (PRP) injections, a novel orthobiologic therapy, for reducing SI joint pain, improving quality of life, and maintaining a clinical effect. METHODS: Short-form McGill Pain Questionnaire (SFM), Numeric Rating Scale (NRS), and Oswestry Low Back Pain and Disability Index were used for evaluation of treatment at pretreatment, 12-months and 48-months after treatment. RESULTS: At follow-up 12-months post-treatment, pooled data from all patients reported a marked improvement in joint stability, a statistically significant reduction in pain, and improvement in quality of life. The clinical benefits of PRP were still significant at 4-years post-treatment. CONCLUSIONS: Platelet-rich plasma therapy exhibits clinical usefulness in both pain reduction and for functional improvement in patients with chronic SI joint pain. The improvement in joint stability and low back pain was maintained at 1- and 4-years post-treatment. PMID- 27392849 TI - Rheological alteration of erythrocytes exposed to carbon nanotubes. AB - Single-walled carbon nanotubes (SWNTs) have been increasingly used in a variety of biomedical applications, such as in vivo delivery of drugs and tumor imaging. Potential exposure of SWNTs to human red blood cells (RBCs) may cause serious toxicity including alteration of mechanical properties of cells. The present study investigated the cellular response to exposure of SWNTs with measuring rheological characteristics of RBCs, including hemolysis, deformability, aggregation, and morphological changes. RBCs were exposed to two different dispersion-state samples (i.e. individual SWNTs and bundled SWNTs) in chitosan hydroxyphenyl acetamide (CHPA) solutions. The concentrations of SWNTs were carefully chosen to avoid any hemorheological alterations due to hemolysis. Rheological characteristics were measured using microfluidic-laser diffractometry and aggregometry. Our results show that the bundled SWNTs had higher hemolytic activity than did the individual SWNTs. RBC aggregation apparently decreased as the concentration of SWNTs or incubation time increased. Additionally, bundled SWNTs caused significant alterations in the shape and fusion of RBCs. In conclusion, bundled SWNTs were found to be more toxic than individual SWNTs. These results provide important insights into the interactions between RBCs and SWNTs and will facilitate assessment of the risk of nanomaterial toxicity of blood. PMID- 27392850 TI - The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-beta Oligomers. AB - 15B3 is a monoclonal IgM antibody that selectively detects pathological aggregates of the prion protein (PrP). We report the unexpected finding that 15B3 also recognizes oligomeric but not monomeric forms of amyloid-beta (Abeta)42, an aggregating peptide implicated in the pathogenesis of Alzheimer's disease (AD). The 15B3 antibody: i) inhibits the binding of synthetic Abeta42 oligomers to recombinant PrP and neuronal membranes; ii) prevents oligomer-induced membrane depolarization; iii) antagonizes the inhibitory effects of oligomers on the physiological pharyngeal contractions of the nematode Caenorhabditis elegans; and iv) counteracts the memory deficits induced by intracerebroventricular injection of Abeta42 oligomers in mice. Thus this antibody binds to pathologically relevant forms of Abeta, and offers a potential research, diagnostic, and therapeutic tool for AD. PMID- 27392851 TI - Mitochondrial Regulatory Pathways in the Pathogenesis of Alzheimer's Disease. AB - Alzheimer's disease (AD) is an age-associated neurodegenerative brain disorder with progressive cognitive decline that leads to terminal dementia and death. For decades, amyloid-beta (Abeta) and neurofibrillary tangle (NFT) aggregation hypotheses have dominated studies on the pathogenesis and identification of potential therapeutic targets in AD. Little attention has been paid to the mitochondrial molecular/biochemical pathways leading to AD. Mitochondria play a critical role in cell viability and death including neurons and neuroglia, not only because they regulate energy and oxygen metabolism but also because they regulate cell death pathways. Mitochondrial impairment and oxidative stress are implicated in the pathogenesis of AD. Interestingly, current therapeutics provide symptomatic benefits to AD patients resulting in the use of preventive trials on presymptomatic subjects. This review article elucidates the pathophysiology of AD and emphasizes the need to explore the mitochondrial pathways to provide solutions to unanswered questions in the prevention and treatment of AD. PMID- 27392852 TI - High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity. AB - The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC(r)1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 MUM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Abeta in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD. PMID- 27392853 TI - PiB-PET Imaging-Based Serum Proteome Profiles Predict Mild Cognitive Impairment and Alzheimer's Disease. AB - Development of a simple, non-invasive early diagnosis platform of Alzheimer's disease (AD) using blood is urgently required. Recently, PiB-PET imaging has been shown to be powerful to quantify amyloid-beta plaque loads leading to pathophysiological alterations in AD brains. Thus, there has been a need for serum biomarkers reflecting PiB-PET imaging data as an early diagnosis platform of AD. Here, using LC-MS/MS analysis coupled with isobaric tagging, we performed comprehensive proteome profiling of serum samples from cognitively normal controls, mild cognitive impairment (MCI), and AD patients, who were selected using PiB-PET imaging. Comparative analysis of the proteomes revealed 79 and 72 differentially expressed proteins in MCI and AD, respectively, compared to controls. Integrated analysis of these proteins with genomic and proteomic data of AD brain tissues, together with network analysis, identified three biomarker candidates representing the altered proteolysis-related process in MCI or AD: proprotein convertase subtilisin/kexin type 9 (PCSK9), coagulation factor XIII, A1 polypeptide (F13A1), and dermcidin (DCD). In independent serum samples of MCI and AD, we confirmed the elevation of the candidates using western blotting and ELISA. Our results suggest that these biomarker candidates can serve as a potential non-invasive early diagnosis platform reflecting PiB-PET imaging for MCI and AD. PMID- 27392854 TI - Diagnosis of Dementia in the Specialist Setting: A Comparison Between the Swedish Dementia Registry (SveDem) and the Registry of Dementias of Girona (ReDeGi). AB - The aim of this study was to compare the frequency of dementia diagnoses from two dementia registries in Europe. Patients registered between 2007 and 2013 in the Swedish Dementia Registry (SveDem; Sweden) and in the Registry of Dementias of Girona (ReDeGi; North-East of Spain) were selected. We compared sociodemographic data, Mini-Mental State Examination (MMSE) scores, dementia subtype, and medication consumption of 22,384 cases from SveDem and 5,032 cases from ReDeGi. The average age (78.1 years SveDem versus 79.7 years ReDeGi) and the gender (female 58.2% SveDem versus 61.5% ReDeGi) did not greatly differ. MMSE score at diagnosis was higher for SveDem cases (22.1 versus 17.8). Alzheimer's disease (AD) accounted for the main dementia subtype (36.6% SveDem versus 55.6% ReDeGi). The proportion of vascular dementia (VaD) and mixed dementia was higher in SveDem (18.8% versus 6.4% and 24.9 versus 13.4%), with an odds ratio (OR) and 95% confidence interval (CI) for SveDem relative to the ReDeGi of 3.41 (3.03-3.84) for VaD, and 2.15 (1.97-2.35) for mixed dementia. This was at the expense of a lower frequency of AD in SveDem (OR 0.41; 95% CI 0.39-0.44). Other dementia diagnoses such as frontotemporal dementia or dementia with Lewy bodies did not significantly differ between registries (2.3% versus 2.9%; 1.9 versus 3.1%). Large differences in medication consumption at the time of dementia diagnosis were detected (4.7 treatments SveDem versus 6.8 ReDeGi). Northern and southern European dementia cohorts differ in demographic characteristics, MMSE score at diagnosis, and drug treatment profile. PMID- 27392856 TI - The Multiple Object Test as a Performance Based Tool to Assess Cognitive Driven Activity of Daily Living Function in Parkinson's Disease. AB - BACKGROUND: There is need for multidimensional quantitative assessment of cognitive driven activities of daily living (ADL) functions in Parkinson's disease (PD). OBJECTIVE: To determine whether there is an ADL profile related to cognitive impairment in PD assessed by the Multiple Object Test (MOT). We assumed MOT performance to be lower in PD patients versus controls and in PD patients with more severe cognitive impairment. METHODS: 50 PD patients with no cognitive impairment (PD-NC), 54 patients with PD-mild cognitive impairment (PD-MCI), 29 with Parkinson's disease dementia (PDD), and 40 healthy controls (HC) were investigated. Besides comprehensive cognitive testing, the MOT, a performance based test consisting of five routine tasks (e.g., preparing a cup of coffee), was applied. Quantitative (total errors and time) and qualitative (error type) MOT parameters were analyzed. RESULTS: Total time and number of MOT errors was increased in PD patients compared to controls (p < 0.001). These parameters also differentiated PDD patients from other cognitive groups (p < 0.05). No control subject had >= 4 errors in the MOT, but 30% of PD patients, especially PDD, scored above this cut-off. Omission (p < 0.001) and mislocation (p < 0.03) errors were more prominent in PDD than other cognitive groups. Perplexity errors did not differ between PD-MCI and PDD but between PD-NC and PDD (p = 0.01). MOT parameters discriminating between cognitive groups correlated mainly with lower test performance in psychomotor speed and executive function. CONCLUSION: Performance based testing is promising to identify quantitative and qualitative ADL aspects differentiating between different cognitive groups which might be helpful for an early detection of PDD. PMID- 27392855 TI - Interaction Between Midlife Blood Glucose and APOE Genotype Predicts Later Alzheimer's Disease Pathology. AB - Elevated blood glucose and the apolipoprotein (APOE) E4 allele have both been associated with increased dementia risk; however, the neuropathological mechanisms underlying these associations remain unclear. We examined the impact of APOE genotype and midlife blood glucose on post-mortem vascular and Alzheimer's disease (AD) neuropathology. Ninety-four participants from the Framingham Heart Study without diagnosed diabetes underwent health examination at midlife and brain autopsy at death. Histopathological measures of vascular and AD neuropathology were obtained and analyzed. Results demonstrated that, among APOE E4 carriers, elevated blood glucose was associated with more severe AD pathology. There was no such relationship with vascular pathology. In a relatively healthy sample with low vascular risk burden, midlife elevated blood glucose was associated with greater AD pathology among APOE E4 carriers. A better understanding of interactive effects of APOE genotype and vascular risk on neuropathology has implications for identification of individuals at risk for decline and long-term preventive treatment. PMID- 27392857 TI - Chronic Stress Aggravates Cognitive Impairment and Suppresses Insulin Associated Signaling Pathway in APP/PS1 Mice. AB - Differences in brain function are a central determinant of individual variability in the stress response. Brain dysfunction, resulting from aging, illness, or genetic mutations, could reduce the tolerance of glucocorticoid stress hormones. When glucocorticoids exceed tolerable limits in the brain, especially in the hippocampus, this state can cause or aggravate structural or functional damage. However, the underlying mechanisms are not well understood. This study investigated the effects of chronic unpredictable mild stress (CUMS) in APP/PS1 and control mice. We showed that 4 weeks of CUMS exposure increased the levels of glucocorticoids, reduced glucocorticoids receptor expression, and promoted senile plaque deposition, neuronal injury, and cognitive impairment in APP/PS1 mice compared to controls. The phosphorylation of insulin receptor, insulin receptor substrate 1 and associated signaling pathways (Akt, mTOR, p70S6K, ERK1/2, and PTEN) were decreased in hippocampus in APP/PS1 mice compared to control mice, while no changes were found in GSK3 and TSC2 phosphorylation. Furthermore, insulin and Akt/mTOR signaling pathways were further decreased in APP/PS1 mice after CUMS, which may be related to the activation of the stress-activated protein kinase JNK, while no alterations in the levels of phosphorylated ERK1/2, GSK3, PTEN, or TSC2 were observed. These results suggest that chronic stress may affect the insulin and Akt/mTOR pathway, accelerating the progression of Alzheimer's disease in vulnerable individuals. PMID- 27392858 TI - Artificial Neural Networks Link One-Carbon Metabolism to Gene-Promoter Methylation in Alzheimer's Disease. AB - BACKGROUND: There is increasing interest in DNA methylation studies in Alzheimer's disease (AD), but little is still known concerning the relationship between gene-promoter methylation and circulating biomarkers of one-carbon metabolism in patients. OBJECTIVE: To detect the connections among circulating folate, homocysteine (hcy) and vitamin B12 levels and promoter methylation levels of PSEN1, BACE1, DNMT1, DNMT3A, DNMT3B, and MTHFR genes in blood DNA. METHODS: We applied a data mining system called Auto Contractive Map to an existing database of 100 AD and 100 control individuals. RESULTS: Low vitamin B12 was linked to the AD condition, to low folates, and to high hcy. Low PSEN1 methylation was linked to low folate levels as well as to low promoter methylation of BACE1 and DNMTs genes. Low hcy was linked to controls, to high folates and vitamin B12, as well as to high methylation levels of most of the studied genes. CONCLUSIONS: The present pilot study suggests that promoter methylation levels of the studied genes are linked to circulating levels of folates, hcy, and vitamin B12. PMID- 27392859 TI - The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer's Disease. AB - BACKGROUND: In diagnosing Alzheimer's disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Abeta1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers. OBJECTIVE: We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Abeta1-42, Abeta1-40, and Abeta1-38. All six analytes were considered as single parameters as well as ratios. METHODS: Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychological (MMSE) examinations for at least one year. RESULTS: The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio. CONCLUSION: This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline. PMID- 27392860 TI - Evolution of the Antidepressant Prescribing in Alzheimer's Disease and Related Disorders Between 2010 and 2014: Results from the French National Database on Alzheimer's Disease (BNA). AB - BACKGROUND: Safety warnings from health authorities are currently intended to limit the use of psychotropic agents in dementia-related conditions. Evidence concerning the use of antidepressants in dementia is, however, scarce and contradictory. OBJECTIVE: To evaluate antidepressant use among individuals with Alzheimer's disease (AD) and related disorders in the French population between 2010 and 2014. METHOD: Antidepressant prescriptions in individuals with AD, mixed dementia (MD), and vascular dementia (VaD) in the French National Alzheimer Database between 2010 and 2014 were analyzed (N = 199,544). RESULTS: Multivariate analysis showed an annual significant increase (p < 0.001) in the prescription rate of antidepressants from 26% (2010) to 31% (2014), and identified female gender, younger age, higher education, living in long-term facilities, more severe cognitive decline, and presence of vascular signs (VaD and MD) as associated factors for antidepressant prescribing. CONCLUSION: The annual increase of antidepressant prescribing among individuals with AD, MD, and VaD in French specialized settings may be partially related to the lack of current valuable medications for dementia-related behavioral symptoms. PMID- 27392861 TI - Moving from the Dish to the Clinical Practice: A Decade of Lessons and Perspectives from the Pre-Clinical and Clinical Stem Cell Studies for Alzheimer's Disease. AB - To date, there is no definitive treatment for Alzheimer's disease (AD). The realm of stem cells is very promising in regenerative medicine, particularly neurodegenerative disorders. Various types of stem cells have been used in multiple trials on AD models, trying to find an innovative management of this disease. In this systematic review, we trace the published preclinical and clinical data throughout the last decade, to show how much knowledge we gained so far in this field and the future perspectives of stem cells in AD treatment. PMID- 27392862 TI - Pharmacological Agents Targeting gamma-Secretase Increase Risk of Cancer and Cognitive Decline in Alzheimer's Disease Patients: A Systematic Review and Meta Analysis. AB - BACKGROUND: Drugs targeting gamma-secretase in Alzheimer's disease (AD) have failed to demonstrate efficacy in clinical trials. OBJECTIVE: To perform a meta analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of drugs targeting gamma-secretase in AD. METHODS: Ten trials were identified involving 5,227 patients using electronic databases and manual review of reference lists. RCTs of at least two weeks duration involving a drug targeting gamma-secretase were eligible. The main outcomes examined were adverse events and cognitive measures (ADAS-cog, MMSE, ADCS-ADL, and CDR-sb). A sub-group analysis was performed, excluding the gamma-secretase modulator tarenflurbil, to evaluate the safety and efficacy of gamma-secretase inhibitors only. RESULTS: There was an increased risk of adverse events (Odds Ratio (OR) 1.38, 95% CI 1.09 1.73; p = 0.01), serious adverse events (OR 1.50, 95% CI 1.22-1.84; p < 0.001), and skin cancers (OR 4.77, 95% CI 2.83-8.06; p < 0.001). There was significantly increased risk of infections (OR 1.36, 95% CI 1.13-1.63; p < 0.001) in the subgroup analysis excluding tarenflurbil. Pooled results also revealed a worsening in ADAS-cog (difference in means 1.33, 95% CI 0.58-2.08; p < 0.001) and MMSE (difference in means -0.66, 95% CI -0.96 to 0.35; p < 0.001), but not ADCS ADL or CDR-sb. CONCLUSION: The use of gamma-secretase inhibitors is associated with significantly increased risk of serious adverse events including skin cancers, and worsening in cognitive indicators. This evidence indicates that gamma-secretase may not be an appropriate target for clinical treatment of AD. PMID- 27392863 TI - Amyloid-beta Reduces Exosome Release from Astrocytes by Enhancing JNK Phosphorylation. AB - Exosomes are small extracellular vesicles secreted by variety of cell types such as neurons, astrocytes, and oligodendrocytes. It is suggested that exosomes play essential role in the maintenance of the neuronal functions and also in the clearance of amyloid-beta (Abeta) from the brain. Abeta is well known to cause neuronal cell death, whereas little is known about its effect on astrocytes. In this study, we examined the effect of Abeta on release of exosomes from astrocytes in culture. We analyzed release of exosomes and apoE, both of which are known to remove/clear Abeta from the brain, in the culture medium of astrocytes. We found that exosome and apoE-HDL were successfully separated by density gradient ultracentrifugation demonstrated by distribution of their specific markers, flotillin and HSP90, and cholesterol, and morphological analysis using electron microscopy. Exosome release was significantly reduced by Abeta1-42 treatment in cultured astrocytes accompanied by an increased JNK phosphorylation. Whereas, apoE-HDL release remained unchanged. A JNK inhibitor restored the decreased levels of exosome release induced by Abeta treatment to levels similar to those of control, suggesting that Abeta1-42 inhibits exosome release via stimulation of JNK signal pathway. Because exosomes are shown to remove Abeta in the brain, our findings suggest that increased Abeta levels in the brain may impair the exosome-mediated Abeta clearance pathway. PMID- 27392864 TI - Time Orientation and 10 Years Risk of Dementia in Elderly Adults: The Three-City Study. AB - Time disorientation is commonly observed in dementia, however very little is known about the pathological significance of minor time errors in community dwelling population. Our objective was to investigate the relationship between time orientation and risk of dementia in a population of older adults. Analyses relies on 8611 dementia-free subjects from the Three-City Study, France. Participants were followed up for 10 years for incident dementia. Time orientation was assessed by asking for the date, the day of the week, the month, the season and the year. At baseline, 905 subjects made at least one error in time orientation. During 57,073 person-years of follow-up, 827 participants developed dementia. After controlling for age, gender and education level, subjects with one error in time had a greater risk of dementia (hazard ratio [HR] 1.44 [1.18-1.77]), while those with at least 2 errors had a more than three-fold increased risk (HR 3.10 [1.98-4.83]). This association was particularly marked for the diagnosis of probable Alzheimer's disease. Time disorientation was associated with an increased risk of dementia in a large population of cognitively normal older people followed during up to 10 years and should not be underestimated in clinical setting. PMID- 27392865 TI - The Role of Capillaries in the Lesser Ailments of Old Age and in Alzheimer's Disease and Vascular Dementia: The Potential of Pro-Therapeutic Angiogenesis. AB - Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and people, including those with Alzheimer's disease. The deficiency of AG factors is analogous to that of certain hormones (e.g., testosterone) whose blood levels also decline with age. In theory, therapeutic angiogenesis employing recombinant AG factors is a tenable treatment for the lesser ailments of old age and may improve the later years of human life. An optimal administration route may be intranasal. PMID- 27392866 TI - Promising Role of Neuromodulation in Predicting the Progression of Mild Cognitive Impairment to Dementia. AB - The differential diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is not always straightforward, and the rate of progression of MCI to dementia is not negligible. Thus, there is a need for para-clinical approaches that can improve the differential diagnosis and identify patients that are at risk of progression. There is a growing interest, at present, in the role of the deterioration of brain oscillations as a predictor of MCI-to-AD conversion. For this reason, we experimentally modulated gamma-band oscillations (GBO) in a sample of MCI and AD patients and an age-matched healthy elderly group, using a transcranial alternating current stimulation (tACS) protocol that was applied to different cortical sites. We correlated the after-effects of tACS on the GBO and the neuropsychological data, in an attempt to differentiate MCI from AD patients and identify, among the MCI patients, those that could be at potential risk of MCI-to-dementia conversion. MCI patients showed a partial GBO increase and improvement in some neuropsychological tests whereas AD individuals did not show significant tACS after-effects. Notably, some MCI subjects lacked significant neuropsychological and electrophysiological after-effects, similar to AD individuals. In a two-year follow-up, such MCI individuals had converted into AD. Therefore, our data suggest that tACS may support the clinical differential diagnosis of MCI and AD and identify MCI patients who could be at risk of developing dementia. This prediction index may help the clinician to adopt a better prevention/follow-up strategy in such a disabling neurodegenerative disease. PMID- 27392867 TI - A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer's Disease. AB - Alzheimer's disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid beta (Abeta) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Abeta clearance by binding apoE/Abeta complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc = 0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Abeta42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD. PMID- 27392868 TI - Mismatch Negativity and Ear Laterality in Alzheimer's Disease and in Mild Cognitive Impairment. AB - BACKGROUND: Cortical auditory event-related potentials (ERPs) were studied in order to measure mismatch negativity (MMN). Three groups of subjects were studied: patients with Alzheimer's disease (AD, n = 32), mild cognitive impairment (MCI, n = 44), and subjective memory complaints without cognitive decline (SMC, n = 27). A bottom up strategy was applied, and the right and left ears were stimulated monaurally. OBJECTIVE: To investigate MMN in AD and MCI, and in a clinical reference group. METHODS: ERPs were carried out with 500 tone pulses at 80 dBnHL. Each sequence included 80% standard tones (500 Hz) (f), and 20% deviant tones (1000 Hz) (r). MMN measurements were carried out by comparing the amplitudes of (f) and (r) recordings and to calculate the amplitude difference in MUV for each group. The right and the left ears were analyzed separately. RESULTS: A left ear advantage (LEA) of MMN amplitude was demonstrated in the two groups with better cognition (the MCI and the SMC groups), but not in the AD group. DISCUSSION: The absence of MMN asymmetry in the AD group is possibly caused by a dysfunction to apprehend changes of tonal stimuli. PMID- 27392869 TI - Protein Misfolding in Prion and Prion-Like Diseases: Reconsidering a Required Role for Protein Loss-of-Function. AB - Prion disease research has contributed much toward understanding other neurodegenerative diseases, including recent demonstrations that Alzheimer's disease (AD) and other neurodegenerative diseases are prion-like. Prion-like diseases involve the spread of degeneration between individuals and/or among cells or tissues via template directed misfolding, wherein misfolded protein conformers propagate disease by causing normal proteins to misfold. Here we use the premise that AD, amyotrophic lateral sclerosis, Huntington's disease, and other similar diseases are prion-like and ask: Can we apply knowledge gained from studies of these prion-like diseases to resolve debates about classical prion diseases? We focus on controversies about what role(s) protein loss-of-function might have in prion diseases because this has therapeutic implications, including for AD. We examine which loss-of-function events are recognizable in prion-like diseases by considering the normal functions of the proteins before their misfolding and aggregation. We then delineate scenarios wherein gain-of-function and/or loss-of-function would be necessary or sufficient for neurodegeneration. We consider roles of PrPC loss-of-function in prion diseases and in AD, and conclude that the conventional wisdom that prion diseases are 'toxic gain-of function diseases' has limitations. While prion diseases certainly have required gain-of-function components, we propose that disease phenotypes are predominantly caused by deficits in the normal physiology of PrPC and its interaction partners as PrPC converts to PrPSc. In this model, gain-of-function serves mainly to spread disease, and loss-of-function directly mediates neuron dysfunction. We propose experiments and predictions to assess our conclusion. Further study on the normal physiological roles of these key proteins is warranted. PMID- 27392871 TI - Anti-Viral Properties of Amyloid-beta Peptides. AB - Amyloid-beta (Abeta) peptides generated by the amyloidogenic pathway of amyloid beta protein precursor processing contribute significantly to neurodegeneration characteristic of Alzheimer's disease (AD). The involvement of Abeta peptides in the etiology of AD remains a subject of debate. Data published in the last 6 years by three different groups have added a new twist by revealing that Abeta peptides could act as antimicrobial peptides (AMP) in in vitro assays against some common and clinically relevant microorganisms, inhibit replication of seasonal and pandemic strains of influenza A and HSV-1 virus. These observations are of significance with respect to the notion that pathogens may be important contributors to the development of AD, particularly in the case of herpes simplex virus (HSV) infection, which often resides in the same cerebral sites where AD arises. Here, we review the data that support the interpretation that Abeta peptides behave as AMP, with an emphasis on studies concerning HSV-1 and a putative molecular mechanism that suggests that interactions between Abeta peptides and the HSV-1 fusogenic protein gB lead to impairment of HSV-1 infectivity by preventing the virus from fusing with the plasma membrane. A number of avenues for future research are suggested. PMID- 27392872 TI - Wearable Sensors for Advanced Therapy Referral in Parkinson's Disease. AB - BACKGROUND: Advanced therapies, such as deep brain stimulation and levodopa carbidopa intestinal gel, can significantly improve quality of life in advanced Parkinson's disease (PD). However, determining who should be referred for advanced therapy is a challenging problem. OBJECTIVE: The objective was to determine the impact of remote monitoring using objective, wearable sensors on the advanced therapy referral rate in patients with advanced PD and if sensor data differed in patients who were referred and those who were not. METHODS: A retrospective, exploratory, secondary analysis was performed on data collected in a study that followed forty individuals with advanced PD for one year with half receiving standard care and half using motion sensor-based remote monitoring once per month in conjunction with standard care. Advanced therapy referral rates were compared between groups. For the group who underwent remote monitoring, objective motor features representing symptoms, dyskinesias, and fluctuations were examined to determine if objective kinematic features differed between patients who were and were not recommended for advanced therapy. RESULTS: The advanced therapy referral rate was significantly higher for patients when a clinician had access to remote monitoring reports compared to standard care alone (63.6% versus 11.8%, p < 0.01). Bradykinesia severity, bradykinesia fluctuations, and dyskinesia severity differed significantly (p < 10e-8, p < 10e-5, and p < 0.01, respectively) between patients recommended and not recommended for advanced therapy. CONCLUSIONS: Remote monitoring technologies can capture motor features that may be clinically useful in identifying patients who may be candidates for advanced therapy. This could lead to development of automated screening algorithms, improve referral efficiency, and expand access to advanced therapies for patients with advanced PD. PMID- 27392873 TI - Characterization of the Enantioselective Properties of the Quinohemoprotein Alcohol Dehydrogenase of Acetobacter pasteurianus LMG 1635. 1. Different Enantiomeric Ratios of Whole Cells and Purified Enzyme in the Kinetic Resolution of Racemic Glycidol. AB - Resting cells of Acetobacter pasteurianus LMG 1635 (ATCC 12874) show appreciable enantioselectivity (E=16-18) in the oxidative kinetic resolution of racemic 2,3 epoxy-1-propanol, glycidol. Distinctly lower values (E=7-9) are observed for the ferricyanide-coupled oxidation of glycidol by the isolated quinohemoprotein alcohol dehydrogenase, QH-ADH, which is responsible for the enantiospecific oxidation step in whole cells. The accuracy of E-values from conversion experiments could be verified using complementary methods for the measurement of enantiomeric ratios. Effects of pH, detergent, the use of artificial electron acceptors, and the presence of intermediate aldehydes, could be accounted for. Measurements of E-values at successive stages of the purification showed that the drop in enantioselectivity correlates with the separation of QH-ADH from the cytoplasmic membrane. It is argued that the native arrangement of QH-ADH in the membrane-associated complex favors the higher E-values. The consequences of these findings for the use of whole cells versus purified enzymes in biocatalytic kinetic resolutions of chiral alcohols are discussed. PMID- 27392874 TI - Isolation and Characterization of a New Quinoprotein Dehydrogenase, L-Sorbose/L Sorbosone Dehydrogenase. AB - Gluconobacter oxydans DSM 4025 effectively oxidizes L-sorbose to 2-keto-L-gulonic acid (2 KGA), an industrial precursor of vitamin C. From this microorganism, we purified the enzyme involved in this oxidation reaction. The enzyme is a unique quinoprotein dehydrogenase catalyzing not only the conversion of L-sorbose to L sorbosone, but also that of L-sorbosone to 2 KGA. The molecular weight of the enzyme was about 135,000, consisting of two subunits with molecular weights of 64,500 and 62,500. As its prosthetic group, non-covalently bound PQQ was found. The dye-linked spectrophotometric enzyme assay showed that the optimum enzyme activity occurred in the pH range about 7.0-9.0, and the enzyme activity was inhibited by EDTA or EGTA. The enzyme showed extremely broad substrate specificity for primary and secondary alcohols, aldehydes, aldoses, ketoses, and other sugar alcohols, but not for methanol or formaldehyde. The cytochrome c obtained from the soluble fraction of this strain was found to act as a physiological electron acceptor of the enzyme. PMID- 27392875 TI - Precursor of alpha-Methylene-gamma-butyrolactone Involved in the Insecticidal Activity of Thunberg Spiraea, Spiraea thunbergii. AB - 6-Tuliposide A {6-O-(4-hydroxy-alpha-methylenebutyryl)-D-glucopyranose} was isolated from thunberg spiraea (Spiraea thunbergii) leaves. Acid-hydrolysis of this compound generated tulipalin A (alpha-methylene-gamma-butyrolactone). This compound is thus considered as a precursor of insecticidal tulipalin A. PMID- 27392876 TI - Identification of L-Bornesitol and Changes in Its Content during Flower Bud Development in Sweet Pea (Lathyrus odoratus L.). AB - An unidentified carbohydrate was isolated from sweet pea (Lathyrus odoratus L. cv. Diana) petals using HPLC. The isolated compound was identified as L-1-O methyl-myo-inositol, called L-bornesitol, using (1)H-NMR, (13)C-NMR, and CI-MS. L Bornesitol was distributed in all organs at high concentrations. L-Bornesitol concentration of petals gradually decreased during flower bud development, but the L-bornesitol content increased by about 5 times. PMID- 27392877 TI - Identification of Endogenous Gibberellins in the Leaves and Xylem Sap of Tea Plants. AB - Endogenous gibberellins (GAs) in the young leaves and xylem sap of tea plants (Camellia sinensis L.) were analyzed by GC-MS. The following GAs were identified by comparing their mass spectra and KRIs with those of authentic specimens: GA9 and GA20 in the leaves; GA9, GA12, GA15, GA20, GA44, GA51 and GA53 in the xylem sap. PMID- 27392878 TI - An Improved Method for Isolating Yeasts in the Genus Lipomyces and Related Genera from Soil. AB - An improved method for isolating soil yeasts in the genus Lipomyces and related genera was developed on the basis of their physiological properties. Liberation of yeast cells from soil, capture of the yeast cells by a membrane filter, and colony formation on an acidic (pH 3) nitrogen-free agar plate containing 0.1% cycloheximide resulted in success. PMID- 27392879 TI - Occurrence in Soybeans of a Novel Vitamin B6 Conjugate that Liberates Pyridoxine by beta-Glucosidase Action after Alkali Treatment. AB - A type of vitamin B6 conjugates (B6X), which liberates free vitamin B6 by alkaline and successive beta-glucosidase hydrolyses, is known to occur in rice bran and wheat bran. Conflicting experimental results, however, have been reported about the occurrence of B6X in soybeans. This study afforded evidence for B6X occuring in soybeans: certainly a highly purified B6X preparation from whole soybeans liberated pyridoxine when it was treated with alkali followed by beta-glucosidase hydrolysis, and 5'-O-(beta-D-glucopyranosyl)pyridoxine by alkali treatment alone. The B6X content varied with cultivars, of which a certain kind contained no B6X. PMID- 27392880 TI - New Method of Screening for Pressure-sensitive Mutants at High Hydrostatic Pressure. AB - We have developed an efficient method of screening to detect pressure-sensitive mutants of barophilic or barotolerant bacteria using conventional agar medium plates. By this new method, 75 colonies can be screened per plate under high hydrostatic pressure. PMID- 27392881 TI - Palladium-catalyzed Substitution Reaction of Allylic Derivatives with Tinacetylene. AB - The substitution reaction of allylic derivatives (acetate, carbonate, and chloride) with tinacetylene proceeded in the presence of palladium as a catalyst to give a product having a 1-ene-4-yne system. PMID- 27392882 TI - Bioactive lipids as new class of microglial modulators: When nutrition meets neuroimunology. AB - Within the central nervous system the traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. More recently, microglia have been found to be important for normal brain development, circuit refinement, and synaptic plasticity in ways that were previously unsuspected. Hence, the brain innate immune system appears to be key in all situations, ranging from physiology to pathology. This unique feature of microglia is established by the wide array of receptors it is equipped with to sense molecular patterns. This includes receptors to most if not all neurotransmitters, neuromodulators and purines. We here review novel, yet extensive literature on a new class of microglia modulators, namely bioactive fatty acids. These lipids are issued from metabolism of nutrients and can cross the blood brain barrier to reach the CNS. They appear to be direct modulators of microglial activity, triggering/inhibiting inflammatory processes or enhancing/inhibiting the ability of these cells to respond to hazardous agents. PMID- 27392883 TI - [Not Available]. AB - BACKGROUND: The "nonrefundable" term use leads to the princep's drug dispensing. The aim of our study was to compare the views of its use between general practitioners and community pharmacists. METHODS: We conducted a descriptive study with similar questionnaires about "nonfundable" term use. A chi-2 test was used in order to detect a difference between the answers of general practitioners ant pharmacists. RESULTS: The general practitioners and pharmacists views of "nonrefundable" used was different (p<0.05). General practitioners majority used this term because of their patients demand. DISCUSSION: General practitioners are using the term "nonrefundable" because of their patients demand and they don't integrate this use in their therapeutics decision. PMID- 27392884 TI - [Not Available]. AB - We describe the case of a woman who developped a cutaneous leukocytoclastic vasculitis following a treatement with gabapentine. PMID- 27392885 TI - Psychometric Properties of the Functional Assessment of Cancer Therapy Neutropenia in Asian Cancer Patients With Chemotherapy-Induced Neutropenia. AB - CONTEXT: The Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) is a neutropenia-specific questionnaire to assess patients' health-related quality of life. OBJECTIVES: This study aimed to examine the psychometric properties of FACT N among cancer patients with chemotherapy-induced neutropenia (CIN). METHODS: This prospective, cross-sectional study included multiethnic Asian cancer patients. Patients completed the questionnaires within seven days after diagnosed with CIN. Eligible patients completed either the English or Chinese version of the EuroQol 5-Dimensions (EQ-5D) and the FACT-N once, according to their language preference. The reliability was evaluated by using Cronbach alpha (alpha). The known-group validity was assessed based on patient's Eastern Cooperative Oncology Group performance status, neutropenia grade, and experience of fever. The convergent validity was evaluated by contrasting the FACT-N subscales with the EQ 5D domains. Multiple linear regression models were performed to compare the FACT N total scores between the two language versions. RESULTS: A total of 276 eligible patients (200 English speaking and 76 Chinese speaking) were included in this study. Internal consistencies within the FACT-N subscales were satisfactory (Cronbach alpha = 0.71-0.85), except for the flu-like symptoms subscale (Cronbach alpha = 0.67). For known-group validity, the FACT-N total score could differentiate patients according to their Eastern Cooperative Oncology Group performance status (P < 0.001), neutropenia grade (P = 0.028), and experience of fever (P < 0.001). The correlations between the FACT-N subscales and their hypothesized constructs in EQ-5D domains were weak to moderate (|r| = 0.15-0.44). The measurement equivalence between the English and Chinese versions was established for the FACT-N total scores. CONCLUSION: The FACT-N is a valid and reliable instrument to be used in clinical practice to evaluate the health related quality of life among multiethnic Asian patients with CIN. PMID- 27392886 TI - scAAV9-VEGF prolongs the survival of transgenic ALS mice by promoting activation of M2 microglia and the PI3K/Akt pathway. AB - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to paralysis and death three to five years after diagnosis in most patients. The disease is incurable, and the mechanism of motoneuron degeneration remains unknown, although research has demonstrated that activated microglia are involved in motor neuron death. Here, we used a simple method to deliver AAV9 virus by direct intrathecal injection and found that scAAV9-VEGF-165 improved the motor performance and prolonged the life span of SOD1-G93A mice. Furthermore, scAAV9-VEGF-165 activated the PI3K/Akt survival pathway and increased the level of Bcl-2, which contributed to the protection of motor neurons. Additionally, scAAV9-VEGF-165 attenuated the expression of classically activated (M1) microglial markers and enhanced the expression of alternatively activated (M2) microglial markers. Taken together, the results of our study suggest that simple, direct intrathecal injection of scAAV9-VEGF-165 may have a curative effect for ALS. PMID- 27392887 TI - Corrigendum to "Generalized CNS arousal: An elementary force within the vertebrate nervous system" [Neurosci. Biobehav. Rev. 68 (2016) 167-176]. PMID- 27392888 TI - Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease. AB - Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10106 Molday ION Rhodamine B-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action. PMID- 27392889 TI - Is Age a Risk Factor for Poor Outcome of Surgical Treatment of Unruptured Intracranial Aneurysms? AB - OBJECTIVE: Advanced age is known to be a significant risk factor for the rupture of intracranial aneurysms. The impact of age on outcomes of surgically treated patients with unruptured intracranial aneurysms (UIAs) is less clear. METHODS: A total of 663 consecutive patients with 823 surgically treated UIAs were evaluated. UIAs, which need bypass surgery including low-flow or high-flow bypass, were defined as complex aneurysms. Aneurysm size was categorized as small (<15 mm), large (15-24 mm), and giant (>=25 mm). In patients without symptoms, a poor outcome is defined as a modified Rankin Scale (mRS) score of 2-6. In those with mRS score higher than 1 as a result of UIA-related symptoms or other comorbidities, a poor outcome is defined as an increase of 1 or more on the mRS. Outcomes were evaluated at the 6-month and 12-month follow-up examinations. RESULTS: The mean age was 62 +/- 12 years and 650 UIAs (78%) were observed in women. Previously treated aneurysm (P = 0.009), posterior circulation aneurysm (P < 0.0001), complex aneurysm (P < 0.0001), a larger size (P = 0.011), and perforator territory infarction (P < 0.0001) were related to poor outcome at 6 months, and posterior circulation aneurysm (P < 0.0001), complex aneurysm (P < 0.0001), a larger size (P = 0.035), and perforator territory infarction (P = 0.013) were related to poor outcome at 12 months. Age was not associated with poor outcome in patients with UIAs who undertook direct surgery. CONCLUSIONS: Although risks and benefits of aneurysm treatment in older patients should be carefully considered, surgical treatment of UIAs in the elderly should be considered positively. PMID- 27392890 TI - Surgical Treatment of Giant Vestibular Schwannomas: Facial Nerve Outcome and Tumor Control. AB - BACKGROUND: Surgical treatment of giant vestibular schwannomas (GVS) is challenging. The philosophy of incomplete tumor resection may balance the preservation of facial nerve function and long-term tumor control. OBJECTIVE: We aimed to evaluate the outcome of facial nerve function and tumor control in treating GVS via our institutional surgical strategy. METHODS: From September 2009 to August 2014, 218 patients who underwent surgical treatment of GVS were enrolled in our study. The clinical features, extent of resections, facial nerve outcome, and the tumor regrowth free rate of these patients were retrospectively analyzed. The treatment strategy of this disease was discussed. RESULTS: All patients had anatomic preservation of the facial nerve. Gross total resection (GTR) was achieved in 58 patients (28.6%), near-total resection (NTR) in 103 (50.7%), and subtotal resection (STR) in 42 (20.7%). Two patients died because of postoperative complications. After a mean follow-up of 39.7 +/- 18.3 months, a favorable facial nerve outcome was achieved in 58.6%, 79.6%, and 83.3% of patients who underwent GTR, NTR, and STR, respectively. During follow-up, 20 patients had tumor regrowth and were treated by stereotactic radiosurgery (SRS), and tumor regrowth free rates were 96.6%, 92.2%, and 76.2% in GTR, NTR, and STR, respectively. The extent of resection was the independent risk factor for poor facial nerve function (P = 0.006). CONCLUSIONS: A surgical philosophy of prioritizing facial nerve preservation over total tumor resection was recommended in treatment of GVS. Favorable facial nerve outcome and tumor control were achieved after NTR of the tumors. PMID- 27392892 TI - Can Feet Help You See Better? Foot Dorsiflexion for Intraoperative Cervical Spine Imaging. PMID- 27392891 TI - The Role of Magnetic Resonance Imaging in the Prediction of Minimally Conscious State After Traumatic Brain Injury. AB - OBJECTIVE: To establish a simple and feasible model of magnetic resonance imaging (MRI) for prediction of minimally conscious state in unconscious patients (>=2 weeks) after severe traumatic brain injury (TBI). METHODS: MRI examinations were performed in 73 patients 4.5 weeks +/- 1.6 (range, 2-8 weeks) after TBI. Brain lesions on MRI, age, sex, cause of injury, Glasgow Coma Scale (GCS) score, and decompressive craniectomy were retrospectively analyzed. Outcome was assessed at 12 months from the onset of TBI. RESULTS: Of 73 patients, 39 were minimally conscious and 34 were unconscious at the endpoint. Binary logistic regression demonstrated that cause of injury (P = 0.036), GCS score (P = 0.011), and lesions of the thalamus (P = 0.002) and brainstem (P = 0.012) shown on MRI were closely associated with the outcome of minimally conscious state. The overall correct prediction of the logistic model was 90.4%. CONCLUSIONS: The combination of MRI findings and other clinical data offers neurosurgeons substantial information about primary and secondary injuries of the patients with TBI, which allows a more accurate prediction of prognosis than a single GCS score or MRI findings alone. The regression model established in this study is simple and effective in predicting long-term unconscious state and minimally conscious state in patients after severe TBI. PMID- 27392893 TI - Endovascular Treatment of 48 Early Branch Aneurysms of the Middle Cerebral Artery. AB - OBJECTIVE: To evaluate the feasibility of endovascular treatment (EVT) for early branch aneurysms (EBAs) of the middle cerebral artery (MCA). METHODS: We reviewed 211 MCA aneurysms that received EVT between January 2012 and December 2014. The EBAs were identified according to their special patterns on cerebral angiography. The angiographic features, clinical outcomes, and angiographic results were investigated. RESULTS: Forty-eight EBAs (22.7%) in 47 patients were identified among the MCA aneurysms. The treatments were successful in all EBAs, including coiling in 23 aneurysms, balloon-assisted coiling in 4, and stent-assisted coiling in 21. Immediate angiograms showed complete occlusion in 15 aneurysms, residual neck in 18, and residual aneurysm in 15. A procedure-related complication occurred in 1 patient (2.1%) who experienced rebleeding during treatment, and no neurologic function was insulted. Thirty-nine patients underwent angiographic follow-up (mean, 8.2 months), which showed 36 aneurysms were not aggravated, 3 had minor recanalization, and none showed major recanalization. The clinical follow-up (mean, 22.8 months) of all patients demonstrated no neurologic deterioration or rebleeding; however, 1 patient died of unexplained cerebral hemorrhage. CONCLUSIONS: Preliminary experience demonstrates that EVT for EBAs is feasible and safe. Direct comparison of clipping and coiling is warranted. PMID- 27392894 TI - Treatment of Unruptured Intracranial Aneurysms and Cognitive Performance: Preliminary Results of a Prospective Clinical Trial. AB - BACKGROUND: Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function. OBJECTIVE: Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs. PATIENTS AND METHODS: Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t1) and 6 weeks after treatment (t2). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes. RESULTS: Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV (P = 0.038) and LD group (P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06). CONCLUSIONS: Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired short-term executive processing in surgically treated patients. PMID- 27392895 TI - Management of Hydrocephalus with Ventriculoperitoneal Shunts: Review of 109 Cases of Children. AB - BACKGROUND: Treatment of hydrocephalus by shunting procedure is associated with variable outcomes, depending on the setting. Results from some published series in sub-Saharan Africa are not so good and various reasons have been given. This study presents preliminary findings of 109 cases of shunted hydrocephalus in children in a 3-year period. OBJECTIVES: The main aim of the study was to evaluate the complications of the procedure in a tertiary-care center. It also seeks to identify ways of reducing such complications where appropriate in subsequent shunt placement procedures. METHODS: A single-institutional retrospective study was conducted by reviewing 124 patients who had ventriculoperitoneal shunting including revisions, and subgroup analysis was performed in 109 patients younger than 18 years classified as children who had first-time shunt placement between January 2011 and December 2013. Data analysis was performed using Microsoft Excel and SPSS (version 20.0). RESULTS: The mean age at shunt insertion of the subgroup was 5.35 years +/- 1.264 standard deviations. Shunt-related complications were identified in 37 of the patients (33.9%). Infections were the most common form of complication, occurring in 16 patients (14.6%). The overall mortality of the 109 patients was 4.59%. CONCLUSIONS: The most common indications for shunt insertions were tumoral and congenital lesions, which may offer us benefit with the use of endoscopic third ventriculostomy. Comprehensive follow-up of these patients may give a better picture of the magnitude of the problem; hence the need for properly designed prospective studies to improve the current outcomes. PMID- 27392896 TI - Role of Intracranial Pressure Monitoring in Management of Patients with Severe Traumatic Brain Injury: Results of a Large Level I Trauma Center in Southern Iran. AB - OBJECTIVE: To determine the role of intracranial pressure (ICP) monitoring in management of patients with severe traumatic brain injury (TBI) admitted to a large level I trauma center in Southern Iran. METHODS: This was a cohort study performed during a 2-year period in a level I trauma center in Southern Iran including all adult patients (>16 years) with severe TBI (Glasgow Coma Scale [GCS] score, 3-8) who underwent ICP monitoring through ventriculostomy. The management was based on the recorded ICP values with threshold of 20 mm Hg. Decompressive craniectomy was performed in patients with intractable intracranial hypertension (persistent ICP >=25 mm Hg). In unresponsive patients, barbiturate coma was induced. Patients were followed for 6 months and Glasgow Outcome Scale Extended was recorded. The determinants of favorable and unfavorable outcome were also determined. RESULTS: Overall, we included 248 patients with mean age of 34.6 +/- 16.6 years, among whom there were 216 men (87.1%) and 32 women (12.9%). Eighty-five patients (34.2%) had favorable and 163 (65.8%) unfavorable outcomes. Those with favorable outcome had significantly lower age (P = 0.004), higher GCS score on admission (P < 0.001), lower Rotterdam score (P = 0.035), fewer episodes of intracranial hypertension (P < 0.001), and lower maximum recorded ICP (P = 0.041). These factors remained statistically significant after elimination of confounders by multivariate logistic regression model. CONCLUSIONS: Age, GCS score on admission, Rotterdam score, intracranial hypertension, and maximum recorded ICP are important determinants of outcome in patients with severe TBI. ICP monitoring assisted us in targeted therapy and management of patients with severe TBI. PMID- 27392897 TI - Superior Sagittal Sinus Obstruction by Giant Meningiomas: Is Total Removal Feasible? AB - OBJECTIVE: To present our experience with microsurgical technique for patients with giant meningiomas (maximum diameter >=7 cm) that obstruct the superior sagittal sinus (SSS). METHODS: All patients who were preoperatively diagnosed (between 2010 and 2014) with giant meningiomas involving the SSS in Ward 10 at the Neurosurgery Department of Beijing Tiantan Hospital were enrolled in this study. Patient charts, imaging findings, and outcomes were examined. RESULTS: The study included 6 male and 4 female patients with a mean age of 46.8 +/- 10.7 years. The tumor sizes varied from 7 to 12 cm (mean, 8.8 +/- 2.0 cm). All patients underwent customized craniotomies, and aggressive surgery for resection of the invaded SSS was performed. Simpson grade I removals were achieved in all cases. No cases of perioperative mortality occurred. Three patients required cranioplasty as a result of a decompressive craniectomy that was performed during the primary surgery. Histologic examinations showed 1 malignant and 9 benign meningiomas. During the follow-up period (mean, 29.0 +/- 9.7 months), recurrence/progression occurred in 1 patient, and 1 patient was lost to follow up. The recent Karnofsky Performance Score was 80 +/- 32.3 and was improved in 5 patients and stabilized in 3 patients. In addition, 7 patients lived independently. CONCLUSIONS: The rigorous preservation of cortical veins, draining veins, and eloquent areas should be implemented during the resection of large tumors that obstruct the SSS. Suitable individualized approaches associated with full exposure and low cerebral perfusion pressure levels after surgery are critical for favorable results, and the reconstruction of the SSS may not be necessary. PMID- 27392898 TI - Prospective Assessment of a Symptomatic Cerebral Vasospasm Predictive Neural Network Model. AB - INTRODUCTION: The author introduced a symptomatic cerebral vasospasm (SCV) prediction model built with freeware based on a 91-patient dataset. In a prospective test group of 22 patients at the same hospital, this model outperformed logistic regression models in vasospasm prediction on the basis of the same datasets. One of the model's limitations was a question of reproducibility in other centers. In this report, the author describes his experience with the prospective use of the model at a different hospital with a different population setting. METHODS: Patient data of 25 consecutive cases of aneurysm rupture were prospectively assessed by the model to predict SCV. The prediction was then compared with actual outcome. For the purpose of this report, SCV is defined as a delayed focal decline in neurological examination correlated with an area of radiographic vasospasm. This serves as the primary end point of the predictive model. Each case prediction is reported, along with strength of prediction, which is built into the model. The model's positive predictive value, negative predictive value, and sensitivity and specificity are reported. RESULTS: Twenty-five patients are included in the analysis. Six patients (24%) were diagnosed with SCV. The model predicted 9 patients would have SCV (positive predictive value 67%). The model predicted 16 patients would not have SCV (negative predictive value 100%). The sensitivity of the model was 100%, and the specificity of the model was 84%. DISCUSSION: The present analysis displays the predictive value of a neural network to model symptomatic cerebral vasospasm. PMID- 27392899 TI - Targeting percutaneous cardiovascular interventions at all who will benefit the most: The reality of the Eastern European countries. PMID- 27392900 TI - PARP inhibition and postinfarction myocardial remodeling. AB - Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt 1/GSK-3beta, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID- 27392901 TI - [Not Available]. AB - AIM: To evaluate the value of research in the case-mix database to identify cases of drug-related anaphylactic or anaphylactoid shock. METHODS: Hospital stays of patients discharged from the University Hospital of Saint-Etienne between July 1st 2009 and June 30th 2012. Five codes from the international classification of diseases were selected: T88.6, T88.2, J39.3, T80.5 and T78.2. RESULTS: Among 89 cases identified by the programme for medicalization of information system (programme de medicalisation des systemes d'information, PMSI), 40 were selected (45%). Of these, 16 cases were spontaneously reported by physicians. The unspecific code "anaphylactic shock unspecified (T78.2)" was coded for 57.5% of cases. CONCLUSION: The study confirms the interest of the PMSI as a tool for health monitoring, in addition to spontaneous reporting. Nevertheless, coding with insufficient precision about the causal role of the drug, requires a return to the medical record and so an important time consuming process. PMID- 27392902 TI - [Not Available]. AB - Tyrosine-kinase inhibitors are recent therapy used in different neoplastic diseases. Dysthyroidism seems to be a class effect of these drugs with a potentially cross cumulative effect. We describe here the case of a man who first developed dysthyroidism with sunitinib, then a deep and permanent hypothyroidism when axitinib was introduced. PMID- 27392903 TI - Pre-Existing Diabetes in Early Stage Breast Cancer Patients is Associated with Lack of Improvement in Quality of Life 2 Years After Diagnosis. AB - PURPOSE: Type 2 diabetes is a common comorbidity among breast cancer survivors. Our aim was to assess the association between diabetes and quality of life (QOL) in newly diagnosed early stage (0-IIA) breast cancer patients over a 2-year follow-up. METHODS: We used data from a longitudinal study of 549 breast cancer patients, aged >=40 years. During four telephone interviews administered 4-6 weeks and 6, 12, and 24 months after definitive surgical treatment, we measured QOL using the Functional Assessment of Cancer Therapy-Breast (FACT-B) scale; higher scores indicate better QOL. Repeated measures analysis of variance was used to test the change over time in total FACT-B and each of the five subscales (physical, social, emotional and functional well-being, and breast cancer concerns), comparing patients with and without diabetes at baseline. RESULTS: After adjusting for covariates (age, race, body mass index, education, marital status, cancer staging, and surgical side effects), patients with (vs. without) diabetes reported lower QOL over time on the total FACT-B (least-squares mean [standard error] 106.2 [2.1] vs. 112.0 [1.1]; p = 0.0038) and on physical, social, emotional, and functional well-being subscales (each p < 0.05). Over the 2-year follow-up, QOL improved significantly for the emotional well-being (p < 0.0001) and breast cancer concern subscales (p = 0.0282) among patients without diabetes, but not among patients with diabetes. CONCLUSION: Early stage breast cancer patients with diabetes may need additional care considerations to improve QOL. PMID- 27392904 TI - Calcitonin effects on shoulder adhesive capsulitis. AB - INTRODUCTION: Adhesive capsulitis (frozen shoulder) is a relatively prevalent disease of shoulder and affects soft tissue of glenohumeral joint. Signs include painful restricted motion and disability of the patient in daily activities. Calcitonin is a thyroid hormone, and its effectiveness has been demonstrated in painful conditions. The presents study aims to evaluate the effect of calcitonin in treating shoulder adhesive capsulitis. METHOD: This double-blinded randomized clinical trial was conducted on 64 patients suffering from shoulder adhesive capsulitis. The intervention and control groups were given intranasal calcitonin and placebo for 6 weeks, respectively. For both groups, physiotherapy and non steroidal anti-inflammatory drugs were administered correspondingly. The patients were evaluated pre- and post-treatment for shoulder pain and shoulder range of motion (ROM). Shoulder functional outcome (secondary outcome) was evaluated using Disability of Arm, Shoulder, and Hand, Shoulder Pain and Disability Index, and Health Assessment Questionnaire disability criteria. RESULTS: The mean age of patients in calcitonin and control group was 52.4 +/- 4.6 and 53.2 +/- 4.9, respectively. Demographic characteristics and pre-treatment scores were similar in both groups (all P > 0.05). In post-treatment follow-up, shoulder pain, ROM, and the patients' functional scores were significantly improved in both groups (P < 0.001); however, the improvement in calcitonin group was more effective than that of placebo group. CONCLUSION: Intranasal calcitonin spray could be an additional safe alternative in shoulder adhesive capsulitis with regard to the efficiency in alleviating pain and improving functional outcome. LEVEL OF EVIDENCE: II. PMID- 27392905 TI - Low prevalence of Plasmodium malariae and Plasmodium ovale mono-infections among children in the Democratic Republic of the Congo: a population-based, cross sectional study. AB - BACKGROUND: In an effort to improve surveillance for epidemiological and clinical outcomes, rapid diagnostic tests (RDTs) have become increasingly widespread as cost-effective and field-ready methods of malaria diagnosis. However, there are concerns that using RDTs specific to Plasmodium falciparum may lead to missed detection of other malaria species such as Plasmodium malariae and Plasmodium ovale. METHODS: Four hundred and sixty six samples were selected from children under 5 years old in the Democratic Republic of the Congo (DRC) who took part in a Demographic and Health Survey (DHS) in 2013-14. These samples were first tested for all Plasmodium species using an 18S ribosomal RNA-targeted real-time PCR; malaria-positive samples were then tested for P. falciparum, P. malariae and P. ovale using a highly sensitive nested PCR. RESULTS: The prevalence of P. falciparum, P. malariae and P. ovale were 46.6, 12.9 and 8.3 %, respectively. Most P. malariae and P. ovale infections were co-infected with P. falciparum-the prevalence of mono-infections of these species were only 1.0 and 0.6 %, respectively. Six out of these eight mono-infections were negative by RDT. The prevalence of P. falciparum by the more sensitive nested PCR was higher than that found previously by real-time PCR. CONCLUSIONS: Plasmodium malariae and P. ovale remain endemic at a low rate in the DRC, but the risk of missing malarial infections of these species due to falciparum-specific RDT use is low. The observed prevalence of P. falciparum is higher with a more sensitive PCR method. PMID- 27392906 TI - Elucidation of a novel phenformin derivative on glucose-deprived stress responses in HT-29 cells. AB - Recently, we developed a variety of phenformin derivatives as selective antitumor agents. Based on previous findings, this study evaluated a promising compound, 2 (2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on the basis of stress responses in the human colon cancer cell line HT-29 under a serum- and glucose-deprived condition. 2-Cl-Phen triggered morphological changes such as shrinkage and plasma membrane disintegration, as well as a decrease in mitochondrial activity and an increase in LDH leakage. To understand intracellular issues relating to 2-Cl Phen, this study focused on the expression levels of ER stress-inducible genes and several oncogenic genes. Serum and glucose deprivation significantly induced a variety of ER stress-inducible genes, but a 12-h treatment of 2-Cl-Phen down regulated expression of several ER stress-related genes, with the exception of GADD153. Interestingly, the expression levels of ATF6alpha, GRP78, MANF, and CRELD2 mRNA were almost completely decreased by 2-Cl-Phen. This study also observed that a 24-h treatment of 2-Cl-Phen attenuated the expression levels of GRP78, GADD153, and c-Myc protein. The decrease in c-Myc protein occurred before the fluctuation of GRP78 protein, while the expression of c-Myc mRNA showed little change with cotreatment of serum and glucose deprivation with 2-Cl-Phen. To further understand the 2-Cl-Phen-induced down-regulation of ATF6-related genes, this study investigated the stability of ATF6alpha and GRP78 proteins using NanoLuc-tagged constructs. The expression levels of NanoLuc-tagged ATF6alpha and GRP78 were significantly down-regulated by 2-Cl-Phen in the presence or absence of the translation inhibitor cycloheximide. Taken together, our novel phenformin derivative 2-Cl-Phen has the unique characteristic of diminishing tumor adaptive responses, especially the expression of ATF6-related genes, as well as that of c-Myc protein, in a transcriptional and posttranscriptional manner under a serum- and glucose-deprived condition. Further characterization of cytotoxic mechanisms related to phenformin derivatives may give new insights into developing additional promising anticancer agents. PMID- 27392907 TI - Lipopolysaccharide promotes pulmonary fibrosis in acute respiratory distress syndrome (ARDS) via lincRNA-p21 induced inhibition of Thy-1 expression. AB - Acute respiratory distress syndrome (ARDS) is a common clinical disorder characterized by pulmonary edema leading to acute lung damage and arterial hypoxemia. Pulmonary fibrosis is a progressive, fibrotic lung disorder, whose pathogenesis in ARDS remains speculative. LincRNA-p21 was a novel regulator of cell proliferation, apoptosis and DNA damage response. This study aims to investigate the effects and mechanism of lincRNA-p21 on pulmonary fibrosis in ARDS. Purified 10 mg/kg LPS was dropped into airways of C57BL/6 mice. Expression levels of lincRNA-p21 and Thy-1 were measured by real-time PCR or western blotting. Proliferation of lung fibroblasts was analyzed by BrdU incorporation assay. Lung and BAL collagen contents were estimated using colorimetric Sircol assay. LincRNA-p21 expression was time-dependently increased and Thy-1 expression was time-dependently reduced in a mouse model of ARDS and in LPS-treated lung fibroblasts. Meanwhile, lung fibroblast proliferation was also time-dependently elevated in LPS-treated lung fibroblasts. In addition, lung fibroblast proliferation could be promoted by lincRNA-p21 overexpression and LPS treatment, however, the elevated lung fibroblast proliferation was further abrogated by Thy 1 overexpression or lincRNA-p21 interference. And Thy-1 interference could elevate cell viability of lung fibroblasts and rescue the reduction of lung fibroblast proliferation induced by lincRNA-p21 interference. Moreover, lincRNA p21 overexpression dramatically inhibited acetylation of H3 and H4 at the Thy-1 promoter and Thy-1 expression levels in HLF1 cells. Finally, lincRNA-p21 interference rescued LPS-induced increase of lung and BAL collagen contents. LincRNA-p21 could lead to pulmonary fibrosis in ARDS by inhibition of the expression of Thy-1. PMID- 27392908 TI - Vitamin D nutritional status and vitamin D regulated antimicrobial peptides in serum and pleural fluid of patients with infectious and noninfectious pleural effusions. AB - BACKGROUND: Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and beta-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before. METHODS: Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25 (OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and beta-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann-Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis. RESULTS: Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum beta-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH)2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best. CONCLUSIONS: Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of beta defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions. PMID- 27392909 TI - Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: assessment of clinical usefulness in CKD patients with atorvastatin (ASUCA) trial. AB - BACKGROUND: Dyslipidemia is a risk factor for the progression of chronic kidney disease (CKD). While conventional lipid lowering therapy provides a benefit to CKD management, the effect of statins on eGFR remains unclear. METHODS: A prospective, multi-center, open-labeled, randomized trial. Total of 349 CKD patients with hyperlipidemia were randomized into 2 groups, and followed for 2 years. Group A included patients who were treated with atorvastatin. Group C were treated with conventional lipid lowering drugs other than statin. Primary endpoint was changes in eGFR. Secondary endpoints included changes in urinary albumin excretion, serum LDL-C, serum triglyceride, cardio-vascular events and all-cause mortality. RESULTS: As the primary endpoint, eGFR decreased by 2.3 ml/min/1.73 m2 in Group A and by 2.6 ml/min/1.73 m2 in Group C, indicating that there was no difference in change of eGFR between the two groups. As secondary endpoints, atorvastatin succeeded to reduce serum LDL-C level significantly and rapidly, but conventional therapy did not. In fact, mean LDL-C level did not reach the target level of 100 mg/dl in Group C. Serum triglyceride was lowered only by atorvastatin, but not conventional drugs. The number of cardiovascular events and all-cause mortality did not differ between in two groups. CONCLUSION: The ASUCA (Assessment of Clinical Usefulness in CKD Patients with Atorvastatin) trial demonstrated that atorvastatin failed to exhibit reno-protections compared to conventional therapy in Japanese patients with dyslipidemia and CKD. It would be due in part to the ability of atorvastatin to more potently reduce serum LDL and triglycerides compared to conventional therapy. PMID- 27392910 TI - Renal parenchymal invasion by metastatic breast cancer. PMID- 27392911 TI - Physical function at the time of dialysis initiation is associated with subsequent mortality. AB - BACKGROUND: In dialysis patients, physical function is associated with mortality. However, the association between physical function at the time of dialysis initiation and subsequent mortality remains unknown. METHODS: A total of 1496 patients with chronic kidney disease who initiated dialysis at 17 centers participating in the Aichi Cohort Study of the Prognosis in Patients Newly Initiated into Dialysis, a multicenter prospective cohort study, were included. The patients were divided into the high (H)-, middle (M)-, and low (L)-score groups according to Barthel index (BI) at the time of dialysis initiation, and the all-cause, cardiovascular disease (CVD)-related, and infection-related mortality rates were compared. Moreover, factors affecting all-cause mortality were investigated. The effects of BI on mortality were assessed in the patients stratified by age, sex, and history of CVD or cerebral infarction. RESULTS: A log rank test for the Kaplan-Meier survival curve showed significant differences between the three groups in all-cause, CVD-related, and infection-related mortality rates (p < 0.001). Cox proportional hazard regression analysis with the step-wise method showed a significantly higher risk of all-cause mortality in the M and L groups than in the H group (M group: HR 1.612, 95 % CI 1.075-2.417; L group: HR 1.994, 95 % CI 1.468-2.709). Regardless of the age categories and the history of CVD, the risk of all-cause mortality was significantly higher in the L group than in the H group. CONCLUSION: Physical function assessed by BI at the time of dialysis initiation was found to be associated with subsequent mortality. PMID- 27392912 TI - Cyclodialysis: an update. AB - Cyclodialysis is the result of the separation of the longitudinal ciliary muscle fibers from the scleral spur, which creates an abnormal pathway for aqueous humor drainage that may lead to ocular hypotony. For many years cyclodialysis was considered a treatment option for glaucoma. However, today it usually occurs as a complication of blunt trauma or more rarely as a complication of anterior segment ocular surgery. Ocular hypotony can lead to cataract development, optic disk swelling, refractive changes, and several retinal complications, making accurate identification and timely intervention of the cleft mandatory. Traditionally gonioscopy was the only available technique to diagnose and localize the cleft. However, other tests such as optical coherence tomography, magnetic resonance imaging, transillumination, and specially ultrasound biomicroscopy are now available for the diagnosis of cyclodialysis. Multiple treatment options are also available for this condition. Although medical treatment can be effective to close small clefts, surgery is needed in most patients to restore ocular pressure. PMID- 27392913 TI - Efficacy of reduced-fluence photodynamic therapy for central serous chorioretinopathy associated with combined serous retinal detachment and fovea involving pigment epithelial detachment. AB - The purpose of the study was to evaluate the effect of reduced-fluence photodynamic therapy (RFPDT) for chronic central serous chorioretinopathy (CSC) associated with serous retinal detachment (SRD) and fovea-involving pigment epithelial detachment (PED). Ten eyes of ten patients with chronic CSC associated with combined SRD and PED involving the fovea were included. RFPDT was applied to the hyperfluorescent area identified at the mid-to-late phase of indocyanine green angiography, which indicated the area of leakage. We evaluated the changes in best-corrected visual acuity (BCVA) and optical coherence tomography at month 1 and final follow-up visit. The mean age of the participants was 47.4 +/- 7 years. The mean follow-up duration was 6.3 +/- 4 months. At month 3, the SRD had resolved completely in all ten eyes (100 %), and PED had resolved in seven eyes (70 %). The initial mean BCVA improved from 20/50 at baseline to 20/32 at the last visit (P > 0.05). The mean central retinal thickness was reduced from 534 +/ 279 um at baseline to 194 +/- 46 um at the last examination (P < 0.001). The mean subfoveal choroidal thickness decreased from 461 +/- 57 at baseline to 369 +/- 75 at the final visit (P < 0.001). Reduced-fluence PDT appears as an effective treatment for chronic CSC cases associated with SRD and fovea-involving PED. PMID- 27392914 TI - Comparison of the measurements of a novel optical biometry: Nidek AL-Scan with Sirius and a ultrasound biometry. AB - To investigate the accuracy of the measurements of Nidek AL-Scan by comparing with Sirius (CSO, Florence, Italy), a corneal tomography which also employs the Scheimpflug principle, and a commonly used device, ultrasound biometry (UB) (Aviso A/B, Quantel Medical, MT, USA). Right eyes of 85 healthy volunteers (58 women 27 men) with a mean age of 39.24 +/- 14.37 years (range 15-68) were enrolled into this comparative prospective study. Average K 2.4, average K 3.3, CCT (central corneal thickness), WTW (white to white distance), ACD (anterior chamber depth) and AL (axial length) were obtained from the AL-Scan and compared with average SimK, CCT, WTW (horizontal anterior chamber diameter) and ACD obtained from Sirius and also compared with ACD and AL obtained from UB. The statistically significant difference was found between all of the measurements (p < 0.001) except the average keratometry values (K2.4, K3.3, SimK) (p = 0.083). There was a perfect correlation between keratometry, CCT and AL measurements of the devices (ICC = 0.977, 0.954, 0.923, respectively) and there was a strong correlation between the WTW measurements of AL-Scan and Sirius (ICC = 0.865). While ACD parameter of AL-Scan and UB showed a perfect correlation (ICC = 0.977), there was a moderate correlation between AL-Scan and Sirius and also between UB and Sirius (ICC = 0.608 and 0.664, respectively). There was a high correlation between the all measurements, besides ACD, of AL-Scan and Sirius and they can be used interchangeably for average keratometry and WTW confidently. However, ACD and CCT have a broader 95 % LoA (-0.039 to 0.744 and -24.985 to 3.691, respectively). In addition, AL-Scan and UB were in good agreement regarding ACD, while differences in AL measurements of UB and AL-Scan were clinically important (95 % LoA = -0.091 to 0.703). Furthermore, UB and Sirius have a moderate agreement regarding ACD (95 % LoA = -0.047 to 0.680). PMID- 27392916 TI - [Not Available]. AB - Sleep disturbances are frequent in children and adolescents with psychiatric disorders nevertheless there are few drugs available to treat them. Only certain antihistaminic H1 have the marketing authorization for treatment of childhood insomnia. Very few studies have been made in children about the hypnotics that are most widely used in adult patients: zopiclone, zolpidem and the hypnotic benzodiazepines. However, melatonin has recently become the most studied hypnotic drug in children since the marketing of a sustained-released form gave it the status of a drug and improved its pharmacokinetic properties. In child psychiatry, pharmacological treatment of insomnia should be considered in patients with attention deficit hyperactivity disorder in which sleep disturbances can be aggravated by psycho stimulant treatment, in autism spectrum disorders, and in the anxiety/depression. PMID- 27392917 TI - [Not Available]. PMID- 27392915 TI - Efficacy of delayed treatment of China-made Peramivir with repeated intravenous injections in a mouse influenza model: from clinical experience to basal experiment. AB - BACKGROUND: China-made Peramivir, an anti-influenza neuraminidase inhibitor drug, is manufactured and widely used in China. Although effective if initiated within 48 h of the onset of symptoms, yet we observed that this drug shows an inconclusive efficacy if treatment is delayed in clinical. Thus we evaluated the efficacy of delayed treatment of China-made Peramivir in a mouse model. METHODS: The mouse model of influenza infection was made and Peramivir was administered intravenously for 5 days following infection, and weight loss, lung index, viral shedding and survival rates were monitored. RESULTS: Peramivir (60 mg/kg . d, repeated intravenous injections, quaque die (QD) * 5 days) enhanced survival rate and suppressed weight loss when treatment was initiated 24, 36, 48, or even 60 h post-infection (p.i.) (p < 0.01), compared with the virus-untreated group, and efficacy was abolished at 72 h p.i.. However the efficacy of delayed treatment was dose dependent, with the highest dose (90 mg/kg . d) even showing efficacy at 72 h p.i.. Furthermore, Peramivir (60 mg/kg . d, repeated intravenous injections, QD * 5 days) also reduced the lung virus titer 24 and 36 h p.i. on day 5, and even at 48 and 60 h p.i. on day 7 after infection, and the lung index was also improved. What is interesting that the concentration of the drug was maintained in blood after infected. CONCLUSIONS: Delayed treatment with China-made Peramivir can reduce the severity of influenza disease, accelerate viral clearance and enhance the survival rate. This drug therefore shows good efficacy and is a promising candidate to control the influenza epidemic in China. PMID- 27392918 TI - [Not Available]. AB - Topiramate, a second generation anticonvulsant drug, is marketed in France since 1997. It is also indicated in the prophylaxis of headache and is used, except legal notices, in the treatment of neuropathic pains and bipolar disorders. The efficiency and the risk of adverse reactions are dose dependent. However, the good correlation between the dosage and the plasmatic concentrations, and the relatively low interindividual variability, when we take into account the age and the association with an enzyme inducer, are not in favour of the interest of a dosage. Furthermore, there is a covering range between the effective and not effective concentrations, and levels susceptible or not to facilitate the appearance of an adverse event. There is no validated therapeutic range, but to the usual dosages the plasma concentrations are included between 5 and 20 mg/L(15 60 |imo]/L), mostly in the low part of this interval. For this molecule, the level of proof of the interest of the TDM was estimated in: possibly useful. PMID- 27392919 TI - [Not Available]. AB - Vigabatrin is a second generation anticonvulsant drug available in France since 1995. It is an amino acid analogue of the GABA, marketed under the racemic form [R(-)/S(+)50/50], but only the S(+)-enantiomer is active. Neither the mechanism of action of vigabatrin, an irreversible enzymatic inhibition, nor its pharmacokinetic characteristics (no binding to plasma proteins, low metabolism, no interaction with CYP), are in favour of TDM. There is no validated therapeutic range, but to the recommended dosage of 1 to 3g a day correspond plasma concentrations ranging from 0,8 to 36 mg/L (6 - 279 umol/L). For this molecule, the level of proof of the interest of the TDM was estimated in: to be useless. PMID- 27392920 TI - Suivi therapeutique pharmacologique du zonisamide. AB - Zonisamide is a second generation antiepileptic drug available in France since 2005. It provides a mechanism of action similar to those of phenytoin or carbamazepine. It is indicated in association in the treatment of partial epilepsy with or without secondary generalization. Zonisamide is well absorbed with maximum concentration achieved in 2 to 5h. It is partly metabolized by the CYP3A4. Its elimination half-life is very long, around 60h. Studies in adults and children show low concentration-efficacy and concentration-toxicity correlations, but a therapeutic range has been determined between 10 and 40 mg/L. Zonisamide is sensitive to the inductive molecules of CYP which will increase its clearance and decrease its half-life. A specific monitoring of patient is recommended in renal impairment. For this molecule, the interest of TDM has been evaluated: possibly useful. PMID- 27392921 TI - Suivi therapeutique pharmacologique du felbamate. AB - Felbamate is a derivative of meprobamate used in second-line partial epilepsy and in the Lennox-Gastaut syndrome. Felbamate is well absorbed and has linear kinetics: Cmax and AUC increasing linearly with dose. The metabolism takes place in the liver. Metabolites represent 40 to 60% of excretion and are eliminated via the urine. The half-life is between 15 and 23 hours. Clearance is dependent on renal function. There is a concentration - efficacy and concentration - toxicity relationship. These arguments are in favour of a TDM but the therapeutic range is not clearly established. Potentially fatal side effects can be caused by felbamate (aplastic anemia, acute liver failure), which limits its use because they are dose-independant. PMID- 27392922 TI - Suivi therapeutique pharmacologique de la lamotrigine. AB - Lamotrigine is a second generation anticonvulsant drug available in France since 1996. As other anticonvulsant drugs, lamotrigine is also used in type I bipolar disorders and except legal notices, in the treatment of neuropathic pains. It is mainly metabolized by the UDP-glucuronyltransferase in inactive metabolites. Its average half-life of elimination is of the order of 22 h, but it is reduced approximately at 14h if it is associated with enzymatic inductors and increased at 70h if lamotrigine is administered with sodium valproate. The pharmacokinetic parameters are modified at the young child's, but not in the old population. During the pregnancy, the plasmatic concentrations are lowered and re-increase strongly after the delivery, if dosages were adapted. The renal insufficiency does not require adaptation of dosage, on the other hand in case of severe hepatic insufficiency a decrease of the dose is to be considered. The correlation concentration-efficiency does not seem demonstrated, but there are not enough published studies and they included few patients. Furthermore, they were led with a methodology more pragmatic than rigorous. The correlation concentration toxicity is better argued. The recommended therapeutic range is from 2.5 to 15 mg/L. For this molecule, the level of proof of the interest of the TDM was estimated in: possibly useful. PMID- 27392923 TI - Suivi therapeutique pharmacologique de la pregabaline. AB - Pregabaline, a second generation antiepileptic, is marketed in France since 2005. It is also indicated in the treatment of painful neuropathy and in generalized anxious disorder. Its pharmacokinetic profile: low metabolism and no binding to plasma proteins, is not in favour of the necessity of a TDM. But other studies would be necessary to concluded more definitively. Pregabalin however, required a dosage adjustment in case of renal insufficiency. The values of the plasma concentrations found after various doses are in agreement in the different studies, without that we can define a therapeutic range. For this molecule, the level of proof of the interest of TDM was estimated in: remaining to estimate. PMID- 27392924 TI - [Not Available]. AB - Tiagabine, a second-generation anticonvulsant drug, is marketed in France since 1997. It is also prescribed outside marketing authorization in the treatment of anxiety. They are few studies allowing arguing a relation exposure efficiency or toxicity, but intra and inter individual important variations in serum concentrations are described. Hepatic insufficiency requires a dose adaptation. In patients treated with therapeutic dose, serum levels are between 20 and 100 MUg/L (50-250 nmol/L) For this molecule, the level of proof of the interest of TDM was estimated in: remaining to estimate. PMID- 27392925 TI - [Not Available]. AB - Gabapentin is a structural analogue of GABA used in the treatment of the partial epilepsies of adult and child of more than 12 years, in monotherapy or in association with other anticonvulsant drugs. In association, gabapentin presents the advantage of not interfering with the other anticonvulsant drugs. The interindividual pharmacokinetic variability and the saturable absorption are, with the adaptation in case of renal insufficiency, the only arguments in favor of TDM. During clinical studies, the plasma concentrations of gabapentin were generally included between 2 and 20 mg/L. For this molecule, the level of proof of the interest of therapeutic drug monitoring was estimated in: possibly useful. PMID- 27392926 TI - [Not Available]. AB - Oxcarbazepine is an analogue of carbamazepine, used for the treatment of partial seizure with or without secondary generalization. The two forms R and S of the mono-hydroxylated derivatives (MHD) are responsible for most of the anti convulsant activity and it is the concentrations of MHD that are relevant in therapeutic drug monitoring (TDM). Analysis of currently literature provides no well-established relationship between plasma concentration of MHD and efficiency or toxicity. Although there is not a validated therapeutic range, the residual concentrations of usually observed therapeutic MHD are situated between 12 and 30 mg/L. In certain pathological or physiological circumstances, the pharmacokinetic variability of the oxcarbazepine can be considerable, but this strong unpredictability does not nevertheless justify the TDM of the MHD. Based on the available evidence, TDM of MHD is not routinely warranted but may be possibly useful in specific situations such as pregnancy or renal insufficiency. PMID- 27392927 TI - [Not Available]. AB - Levetiracetam is an anticonvulsant drug used to treat partial seizures, myoclonic seizures of juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures. A review of the literature with an evidence-based medicine method highlighted parameters (age, renal failure, pregnancy, combination with other anticonvulsant drugs) which affect levetiracetam pharmacokinetics but no significant relationship between plasma concentration of levetiracetam and efficacy or toxicity. Concentrations usually observed in therapeutics is from 6 to 18 mg/L. However, the determination of an individual therapeutic concentration, associated with an effective and well tolerated therapy, could be recommended particularly before pregnancy. Consequently, therapeutic drug monitoring of leve-tiracetam which is not currently recommended could be possibly useful in specific clinical situations. PMID- 27392928 TI - Second Meeting of the French CEIP (Centres d'Evaluation et d'Information sur la Pharmacodependance). Part I: How to Evaluate and Prevent the Abuse and Dependence on Hypnotic/Anxiolytic Drugs? AB - Les deuxiemes journees de Pharmacodependances organisees par le reseau francais des CEIP Addictovigilance (Centres d'Evaluation et d'Information sur la Pharmacodependance) se sont tenues lors du congres annuel de la Societe Francaise de Pharmacologie et de Therapeutique en 2008. Elles avaient pour theme l'abus et la pharmacodependance des anxiolytiques et hypnotiques en combinant plusieurs approches pharmacoepidemiologiques, epidemiologiques et therapeutiques. Les donnees presentees en premiere partie ont synthetise l'apport des outils pharmacoepidemiologiques developpes par les CEIP et ont souligne les differences en terme d'abus et de dependance au sein de cette classe des anxiolytiques et hypnotiques. La deuxieme partie a porte sur les caracteristiques de cette consommation a sein de la population agee et a souligne le peu d'informations disponibles sur les facteurs associes a ce comportement, son depistage, son evaluation, son diagnostic et son traitement. PMID- 27392929 TI - p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas. AB - High-grade neuroendocrine carcinomas (HGNECs) of the head and neck have the morphological appearance of undifferentiated carcinomas and could be histologically similar to human papillomavirus (HPV)-associated non-keratinizing squamous cell carcinomas of the head and neck. The aim of the study is to characterize histologically, immunohistochemically, and virologically these unusual neoplasms. Nineteen HGNECs of the head and neck (1 oropharyngeal, 5 sinonasal, 7 of the larynx, and 6 of the parotid gland) were reviewed and analyzed with a immunohistochemical panel, with special emphasis on cell cycle proteins. The tumors were tested for HPV by in situ hybridization (GenPoint HPV, Dako) and PCR (SPF10-DEIA-LiPA25). Merkel cell polyomavirus was studied using the antibody CM2B4. Fifteen HGNEC were of small cell and 4 of large cell type. Most of the tumors (14/19, 73.7 %), including all the pure small cell carcinomas, showed a strong and diffuse positive staining for p16. Eleven of them (78.5 %) had Rb loss and a low or absent cyclin D1 expression. All cases were negative for HPV and polyomavirus. Most patients were smokers, diagnosed at advanced stages of the disease, and had a poor outcome, with a 5-year survival of 18 %. In conclusion, HGNECs of the head and neck are infrequently related to HPV infection, but usually show strong, diffuse positive p16 immunostaining due to Rb pathway dysregulation. Awareness of this immunohistochemical pattern of expression may avoid a potential diagnostic pitfall with HPV-associated non keratinizing squamous cell carcinomas, which have a better prognosis. PMID- 27392930 TI - Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy. AB - Purpose of this study was to evaluate prognostic impact of rare variants of urothelial bladder cancer (BC) after treatment with combined radiochemotherapy (RCT). To this end tumour tissue of 238 patients with urothelial carcinoma (UC) treated with transurethral resection of the bladder (TUR-B) and RCT with curative intent was collected. Histomorphological analysis included re-evaluation and semi quantitative assessment of rare UC subtypes. Additionally, human epidermal growth factor receptor 2 (HER2) chromogenic in situ hybridisation (CISH) was performed in tumours with a micropapillary component exceeding 30 %. Long-term follow-up was available for 200 patients (range 3-282 months). Variant UC histology was found in 45 of 238 tumours, most frequently micropapillary UC (N = 17) including cases with a small fraction of tumour with micropapillary morphology. The mere presence of micropapillary morphology did not affect prognosis. In tumours with extensive (>=30 %) micropapillary morphology (N = 8) Kaplan-Meier analysis revealed significantly worse cancer specific survival (CSS) (P = 0.002) compared to conventional UC (mean survival times 97 months and 229 months, respectively). Univariate Cox regression analysis of cases with >=30 % micropapillary morphology revealed a hazard ratio of 4.726 (95 % CI 1.629-13.714) for CSS (P = 0.004). CISH revealed HER2 gene amplification in 3/10 tumours with >=30 % micropapillary component. In conclusion, for BC treated with TUR-B and RCT, the presence of micropapillary morphology in more than 30 % of the tumour is an adverse prognostic factor. Further studies are needed to evaluate a potential benefit of different, especially multimodal treatment strategies for micropapillary UC and also other subtypes of UC. Her2 represents a promising therapeutic target in a subset of micropapillary UC. PMID- 27392931 TI - Nuclear localization of Toll-like receptor 5 in Barrett's esophagus and esophageal adenocarcinoma is associated with metastatic behavior. AB - Toll-like receptor 5 (TLR5) recognizes bacterial flagellin. Increased cytoplasmic and nuclear expression of some TLRs has been previously reported in dysplasia in Barrett's esophagus and various malignant lesions in association with survival and metastasis. We assessed nuclear expression of TLR5 in Barrett's esophagus and esophageal adenocarcinoma (n = 94) by immunohistochemistry and immunofluorescent staining. Nuclear expression was observed in the majority of studied lesions with high variation in the proportion of positive nuclei. Expression in lymph node metastases was significantly higher than in esophageal lesions (p < 0.05), except for intestinal metaplasia and low-grade dysplasia. Furthermore, nuclear expression of TLR5 was associated with the presence of lymph node metastases (p = 0.033). In conclusion, we report nuclear TLR5 expression in Barrett's esophagus and adenocarcinoma. Abundance of positive nuclei in association with lymph node metastases suggests that TLR5 is involved in the pathogenesis and dissemination of esophageal adenocarcinoma through as-yet-uncharacterized mechanisms. PMID- 27392932 TI - Low-level mediation of directionally specific motion aftereffects: Motion perception is not necessary. AB - Previous psychophysical experiments with normal human observers have shown that adaptation to a moving dot stream causes directionally specific repulsion in the perceived angle of a subsequently viewed moving probe. In this study, we used a two-alternative forced choice task with roving pedestals to determine the conditions that are necessary and sufficient for producing directionally specific repulsion with compound adaptors, each of which contains two oppositely moving, differently colored component streams. Experiment 1 provided a demonstration of repulsion between single-component adaptors and probes moving at approximately 90 degrees or 270 degrees . In Experiment 2, oppositely moving dots in the adaptor were paired to preclude the appearance of motion. Nonetheless, repulsion remained strong when the angle between each probe stream and one component was approximately 30 degrees . In Experiment 3, adapting dot pairs were kept stationary during their limited lifetimes. Their orientation content alone proved insufficient for producing repulsion. In Experiments 4-6, the angle between the probe and both adapting components was approximately 90 degrees or 270 degrees . Directional repulsion was found when observers were asked to visually track one of the adapting components (Exp. 6), but not when they were asked to attentionally track it (Exp. 5), nor while they passively viewed the adaptor (Exp. 4). Our results are consistent with a low-level mechanism for motion adaptation. This mechanism is not selective for stimulus color and is not susceptible to attentional modulation. The most likely cortical locus of adaptation is area V1. PMID- 27392933 TI - Diagnostic methods in ocular argyrosis: case report. AB - PURPOSE: The aim of this report is to present a case of a patient, metal foundry worker, who had been exposed to industrial silver salts for over 20 years. It is well established that chronic exposure to silver compounds can cause accumulation of silver deposits in various tissues. This condition is referred to as argyrosis or argyria, whereas changes related to eye tissues are defined as ocular argyrosis. METHODS: A complete eye examination, corneal confocal microscopy, kinetic and static visual field test, posterior segment optical coherent tomography, pattern visual evoked potentials (PVEP), flash visual evoked potentials, multifocal electroretinogram, pattern electroretinogram (PERG), full field electroretinography (FERG) and electrooculogram were all performed. RESULTS: Eye examination revealed decreased visual acuity, corneal deposits and drusenoid changes within the macula. Although electrophysiology tests did not show changes in the function of retinal pigment epithelium, they revealed abnormal function of photoreceptors in the central and peripheral retina. PERG abnormalities and delayed latency of P100 wave in PVEP confirmed impaired function of the inner layers of the retina in the macular region. CONCLUSIONS: Corneal confocal microscopy and electrophysiological tests may help confirm the diagnosis of ocular argyrosis. PMID- 27392934 TI - Multi-parametric imaging of cell heterogeneity in apoptosis analysis. AB - Apoptosis is a multistep process of programmed cell death where different morphological and molecular events occur simultaneously and/or consequently. Recent progress in programmed cell death analysis uncovered large heterogeneity in response of individual cells to the apoptotic stimuli. Analysis of the complex and dynamic process of apoptosis requires a capacity to quantitate multiparametric data obtained from multicolor labeling and/or fluorescent reporters of live cells in conjunction with morphological analysis. Modern methods of multiparametric apoptosis study include but are not limited to fluorescent microscopy, flow cytometry and imaging flow cytometry. In the current review we discuss the image-based evaluation of apoptosis on the single-cell and population level by imaging flow cytometry in parallel with other techniques. The advantage of imaging flow cytometry is its ability to interrogate multiparametric morphometric and fluorescence quantitative data in statistically robust manner. Here we describe the current status and future perspectives of this emerging field, as well as some challenges and limitations. We also highlight a number of assays and multicolor labeling probes, utilizing both microscopy and different variants of imaging cytometry, including commonly based assays and novel developments in the field. PMID- 27392935 TI - Activation peptide of coagulation factor IX regulates endothelial permeability. AB - Endothelial hyperpermeability is involved in several critical illnesses, and its regulatory mechanisms have been intensively investigated. It was recently reported that the activation peptide of coagulation factor IX enhances cell matrix and intercellular adhesion. The aim of this study was to investigate the role of activation peptide of coagulation factor IX in intercellular adhesion of endothelial cells and evaluate its effects on endothelial permeability. In the presence of activation peptide, cells spread with lamellipodium-like broad protrusions multidirectionally, increasing the area of adhesion to matrix by 16% within 30 minutes. In intercellular adhesion, treatment with activation peptide induced overlapping of adjacent cell edges and remodeling of intercellular adhesion sites, with colocalization of the adherens junction proteins VE-cadherin and beta-catenin and a marker protein of the lateral border recycling compartment, PECAM. Activation peptide decreased gaps between cells by 66% in cultured endothelial cells and suppressed increased endothelial cell monolayer permeability induced by interleukin-1beta in a dose-dependent manner. Treatment with activation peptide decreased eNOS protein expression and altered its subcellular distribution, decreasing intracellular cGMP. An analogue of cGMP suppressed the effects of activation peptide on cell spreading. In addition, the effect of activation peptide on hyperpermeability was investigated in mice injected with lipopolysaccharide. Intravenous injection of lipopolysaccharide increased lung weight by 28%, and treatment with activation peptide significantly suppressed the increase in lung weight to 5%. Our results indicate that activation peptide of factor IX regulates endothelial intercellular adhesion and thus could be used in the treatment of vascular hyperpermeability. PMID- 27392936 TI - Understanding the role of the microbiome in chronic obstructive pulmonary disease: principles, challenges, and future directions. AB - In the past several years, advances in sequencing platforms and bioinformatics have transformed our understanding of the relationship between microbial ecology and human health. Both the normal and diseased lung are host to hundreds of bacterial genera, blurring the lines between "colonization" and "infection". However, whereas in health the respiratory microbiome is determined primarily by the dynamic balance of immigration and elimination, in chronic disease conditions become much more favorable for the reproduction of resident bacteria. Recent studies demonstrate that the microbiota of the chronic obstructive pulmonary disease (COPD) lung differ from the healthy lung although significant intrasubject and intersubject heterogeneity are still present with variation impacted by factors such as disease stage and inhaled medications. Changes in the relative abundance of specific bacterial taxa during COPD exacerbations have also been noted although further longitudinal analyses are needed to ascertain the malleability and resilience of this ecological system and its role in the occurrence and frequency of exacerbations. Whether patients with a "frequent exacerbator" phenotype possess specific or greater alterations in their airway microbiome that predispose them to recurrent exacerbations as compared with nonfrequent exacerbators needs to be determined. Although recent data suggest that the presence of bacteria has the potential to influence the host immune response, a key challenge in the next few years will be to continue to move beyond descriptive studies to define the clinical relevance of differences in lung microbiota associated with COPD. PMID- 27392937 TI - Prophylactic L-arginine and ibuprofen delay the development of tactile allodynia and suppress spinal miR-155 in a rat model of diabetic neuropathy. AB - Diabetic neuropathy (DN) is a common complication of diabetes mellitus that is hardly reversible at the late stages. Since treatment of neuropathic pain is predominantly symptomatic, a prophylactic measure would be useful. Both ibuprofen and L-arginine exert antiallodynic effects on chronic constriction injury (CCI) induced cold allodynia. Furthermore, ibuprofen is effective in CCI-induced mechanical allodynia. The aim of the study was to assess the antiallodynic effect of prophylactic ibuprofen and L-arginine in streptozotocin-induced DN in rats and to further investigate the role of spinal miR-155 and nitric oxide (NO) in this effect. Tactile allodynia was assessed weekly by von Frey filaments. Oral daily administration of ibuprofen, L-arginine and their combination, for 4 weeks starting 1 week after streptozotocin injection (ie, before the development of tactile allodynia), resulted in a significant decrease of tactile allodynia compared with the control diabetic group. This was evident in the fifth week of the experiment. The 3 treatments prevented the decrease in muscle fiber diameter and epidermal thickness, seen in the control diabetic group. Furthermore, ibuprofen, L-arginine and their combination prevented the increase in the spinal NO level and miRNA-155, seen in the control diabetic group. In conclusion, both ibuprofen and L-arginine delayed the development of behavioral and histologic changes of DN, with concomitant suppression of spinal miR-155 and NO level. L arginine being tolerable may be useful prophylactically in diabetic patients. PMID- 27392938 TI - Detection of volatile metabolites of moulds isolated from a contaminated library. AB - The principal fungal species isolated from a contaminated library environment were tested for their microbial volatile organic compound (MVOC) production ability. Aspergillus creber, A. penicillioides, Cladosporium cladosporioides, Eurotium chevalieri, E. halophilicum, Penicillium brevicompactum and P. chrysogenum were cultivated on suitable culture media inside sample bottles specifically designed and created for direct MVOC injection to a GC-MS instrument. The fungal emissions were monitored over several weeks to detect changes with the aging of the colonies, monitored also by respirometric tests. A total of 55 different MVOCs were detected and isopropyl alcohol, 3-methyl-1 butanol and 2-butanone were the principal compounds in common between the selected fungal species. Moreover, 2,4-dimethylheptane, 1,4-pentadiene, styrene, ethanol, 2-methyl-1-butanol, acetone, furan and 2-methylfuran were the most detected compounds. For the first time, the MVOC production for particular fungal species was detected. The species A. creber, which belongs to the recently revised group Aspergillus section Versicolores, was characterized by the production of ethanol, furan and 1,4-pentadiene. For the xerophilic fungus E. halophilicum, specific production of acetone, 2-butanone and 1,4-pentadiene was detected, supported also by respirometric data. The results demonstrated the potential use of this method for the detection of fungal contamination phenomena inside Cultural Heritage's preservation environments. PMID- 27392939 TI - Mephebrindole, a synthetic indole analog coordinates the crosstalk between p38MAPK and eIF2alpha/ATF4/CHOP signalling pathways for induction of apoptosis in human breast carcinoma cells. AB - The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3'-(Arylmethylene)-bis-1H indole (AMBI) derivative 3,3'-[(4-Methoxyphenyl) methylene]-bis-(5-bromo-1H indole), named as Mephebrindole (MPB) as an effective anti-cancer agent in breast cancer cells. MPB disrupted calcium homeostasis in MCF7 cells which triggered ER stress development. Detailed evaluations revealed that mephebrindole by activating p38MAPK also regulated GRP78 and eIF2alpha/ATF4 downstream to promote apoptosis. Studies extended to in vivo allograft mice models revalidated its anti carcinogenic property thus highlighting the role of MPB as an improved chemotherapeutic option. PMID- 27392940 TI - Human NK cells maintain licensing status and are subject to killer immunoglobulin like receptor (KIR) and KIR-ligand inhibition following ex vivo expansion. AB - Infusion of allogeneic NK cells is a potential immunotherapy for both hematopoietic malignancies and solid tumors. Interactions between killer immunoglobulin-like receptors (KIR) on human NK cells and KIR-ligands on tumor cells influence the magnitude of NK function. To obtain sufficient numbers of activated NK cells for infusion, one potent method uses cells from the K562 human erythroleukemia line that have been transfected to express activating 41BB ligand (41BBL) and membrane-bound interleukin 15 (mbIL15). The functional importance of KIRs on ex vivo expanded NK cells has not been studied in detail. We found that after a 12-day co-culture with K562-mbIL15-41BBL cells, expanded NK cells maintained inhibition specificity and prior in vivo licensing status determined by KIR/KIR-ligand interactions. Addition of an anti-CD20 antibody (rituximab) induced NK-mediated antibody-dependent cellular cytotoxicity and augmented killing of CD20+ target cells. However, partial inhibition induced by KIR/KIR ligand interactions persisted. Finally, we found that extended co-cultures of NK cells with stimulatory cells transduced to express various KIR-ligands modified both the inhibitory and activating KIR repertoires of the expanded NK cell product. These studies demonstrate that the licensing interactions known to occur during NK ontogeny also influence NK cell function following NK expansion ex vivo with HLA-null stimulatory cells. PMID- 27392941 TI - Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells. AB - BACKGROUND: Mesoporous silica nanoparticles (MSNs) have been promising vehicles for drug delivery. Quercetin (Q), a natural flavonoid, has been reported to have many useful effects. However, poor water solubility as well as less bioavailability has confined its use as a suitable anti-cancer drug. Therefore, profound approach is required to overcome these drawbacks. METHODS: We have synthesized folic acid (FA) armed mesoporous silica nanoparticles (MSN-FA-Q) loaded with quercetin and then characterized it by DLS, SEM, TEM and FTIR. MTT, confocal microscopy, flow cytometry, scratch assay and immunoblotting were employed to assess the cell viability, cellular uptake, cell cycle arrest, apoptosis, wound healing and the expression levels of different signalling molecules in breast adenocarcinoma cells. Nanoparticle distribution was investigated by using ex vivo optical imaging and CAM assay was employed to assess tumor regression. RESULTS: MSN-FA-Q facilitates higher cellular uptake and allows more drug bioavailability to the breast cancer cells with over-expressed folate receptors. Our experimental results suggest that the newly synthesized MSN FA-Q nanostructure caused cell cycle arrest and apoptosis in breast cancer cells through the regulation of Akt & Bax signalling pathways. Besides, we also observed that MSN-FA-Q has a concurrent anti-migratory role as well. CONCLUSION: This uniquely engineered quercetin loaded mesoporous silica nanoparticle ensures a targeted delivery with enhanced bioavailability. GENERAL SIGNIFICANCE: Effective targeted therapeutic strategy against breast cancer cells. PMID- 27392943 TI - Characteristics of premature ventricular contractions in healthy children and their impact on left ventricular function. AB - BACKGROUND: There are few data regarding the characteristics of premature ventricular contractions (PVCs) in healthy children and their impact on left ventricular (LV) function. OBJECTIVE: The purpose of this study was to assess the prevalence of LV systolic dysfunction in children with frequent PVCs (>=10%) and determine whether it is associated with PVC characteristics (e.g., proportion, coupling interval, width, and/or morphology). METHODS: We conducted a single center cohort study of children with structurally normal hearts and PVC burden >=10% by 24-hour Holter monitoring performed between 2008 and 2012. Clinical, arrhythmic, and echocardiographic data were reviewed at baseline and during follow-up. RESULTS: A total of 47 children (22 female [47%], mean age 8.2 +/- 6.5 years) had a mean PVC burden of 20.9 +/- 11.9% at baseline. The PVC coupling interval averaged 430 +/- 110 ms, with a PVC width of 118 +/- 27 ms. PVCs were monomorphic in 44 patients (94%). Although no patient had severe cardiomyopathy, 7 (15%) had reduced shortening fraction (Z-score <-2). A strong association was observed between PVC coupling interval and LV shortening fraction Z-score <-2.0 (area under the curve 0.95 +/- 0.03, P <.001). A cutoff value <365 ms yielded the greatest discriminatory ability (Youden J-statistic 0.72, sensitivity 85.7%, specificity 86.5%). PVC proportion, width, and morphology were not significantly associated with LV shortening fraction. During 4.0 +/- 2.8 years of follow-up, the PVC burden decreased from a median of 18% to 1.5% (P<.001). CONCLUSION: PVCs in children with structurally normal hearts are associated with a relatively benign course, with spontaneous resolution in most children. Mild LV systolic dysfunction, observed in 15%, is strongly correlated with a shorter coupling interval (<365 ms). PMID- 27392942 TI - Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice. AB - BACKGROUND: In mammals, the majority of the essential amino acid tryptophan is degraded via the kynurenine pathway (KP). Several KP metabolites play distinct physiological roles, often linked to immune system functions, and may also be causally involved in human diseases including neurodegenerative disorders, schizophrenia and cancer. Pharmacological manipulation of the KP has therefore become an active area of drug development. To target the pathway effectively, it is important to understand how specific KP enzymes control levels of the bioactive metabolites in vivo. METHODS: Here, we conducted a comprehensive biochemical characterization of mice with a targeted deletion of either tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO), the two initial rate-limiting enzymes of the KP. These enzymes catalyze the same reaction, but differ in biochemical characteristics and expression patterns. We measured KP metabolite levels and enzyme activities and expression in several tissues in basal and immune-stimulated conditions. RESULTS AND CONCLUSIONS: Although our study revealed several unexpected downstream effects on KP metabolism in both knockout mice, the results were essentially consistent with TDO-mediated control of basal KP metabolism and a role of IDO in phenomena involving stimulation of the immune system. PMID- 27392944 TI - Scar voltage threshold determination using ex vivo magnetic resonance imaging integration in a porcine infarct model: Influence of interelectrode distances and three-dimensional spatial effects of scar. AB - BACKGROUND: Studies analyzing optimal voltage thresholds for scar detection with electroanatomic mapping frequently lack a gold standard for comparison. OBJECTIVE: The purpose of this study was to use a porcine infarct model with ex vivo magnetic resonance imaging (MRI) integration to characterize the relationship between interelectrode spacing and bipolar voltage thresholds and examine the influence of 3-dimensional scar on unipolar voltages. METHODS: Thirty two combined endocardial-epicardial electroanatomic maps were created in 8 postinfarct porcine subjects (bipolar 2-mm, 5-mm, and 8-mm interelectrode spacing and unipolar) for comparison with ex vivo MRI. Two thresholds were compared: (1) 95% normal distribution and (2) best fit to MRI. Direct electrogram analysis was performed in regions across from MRI-defined scar and adjacent to scar border zone. RESULTS: A linear increase in optimal thresholds was observed with wider bipole spacing. The 95% thresholds for scar were lower than MRI-matched thresholds with moderate sensitivity for nontransmural scar (54% endo, 63% epi). Unipolar endocardial scar area exceeded MRI-defined scar, resulting in mismatched false scar in 5 of 8 (63%). Endocardial and epicardial unipolar voltages were lower than normal in regions adjacent and across from scar. CONCLUSION: Variations in interelectrode spacing necessitate tailored bipolar voltage thresholds to optimize scar detection. Statistical 95% thresholds appear to be conservative and not fully sensitive for the detection of scar defined by high resolution ex vivo MRI. In the presence of endocardial scar, unipolar mapping to quantitatively characterize epicardial scar may be overly sensitive due to 3 dimensional spatial averaging. PMID- 27392945 TI - Long-term outcomes after catheter ablation of ventricular tachycardia in patients with and without structural heart disease. AB - BACKGROUND: Long-term outcomes after ventricular tachycardia (VT) ablation are sparsely described. OBJECTIVES: The purpose of this study was to describe long term prognosis after VT ablation in patients with no structural heart disease (no SHD), ischemic cardiomyopathy (ICM), and nonischemic cardiomyopathy (NICM). METHODS: Consecutive patients (N = 695: no SHD, 98; ICM, 358; NICM, 239) ablated for sustained VT were followed for a median of 6 years. Acute procedural parameters (complete success [noninducibility of any VT]) and outcomes after multiple procedures were reported. RESULTS: Compared with patients with no SHD or NICM, patients with ICM were the oldest, were more likely to be men, lowest left ventricular ejection fraction, highest drug failures, VT storms, and number of inducible VTs. Complete procedure success was highest in patients with no SHD than in patients with ICM and those with NICM (79%, 56%, 60%, respectively; P < .001). At 6 years, ventricular arrhythmia (VA)-free survival was highest in patients with no SHD (77%) than in patients with ICM (54%) and those with NICM (38%) (P < .001), and overall survival was lowest in patients with ICM (48%), followed by patients with NICM (74%) and patients with no SHD (100%) (P < .001). Age, left ventricular ejection fraction, presence of SHD, acute procedural success (noninducibility of any VT), major complications, need for nonradiofrequency ablation modalities, and VA recurrence were independently associated with all-cause mortality. CONCLUSION: Long-term follow-up after VT ablation shows excellent prognosis in the absence of SHD, highest VA recurrence, and transplantation in patients with NICM and highest mortality in patients with ICM. The extremely low mortality for those without SHD suggests that VT in this population is rarely an initial presentation of a myopathic process. PMID- 27392946 TI - Thrombus formation at the tip of a leadless pacemaker causing multiple unnecessary repositioning. PMID- 27392947 TI - Metformin discontinuation less than 72 h is suboptimal for F-18 FDG PET/CT interpretation of the bowel. AB - OBJECTIVE: Metformin-induced [F-18] fluorodeoxyglucose (FDG) bowel uptake can hinder positron emission tomography/computed tomography (PET/CT) evaluation of the bowel. This study aimed to investigate the segmental bowel uptake of FDG according to metformin discontinuation times up to 72 h. METHODS: We retrospectively divided 240 diabetic patients into four groups: metformin discontinuation <24 h (group A; n = 86), 24-48 h (group B; n = 40), 48-72 h (group C; n = 12), and no metformin (control group; n = 102). Segmental FDG bowel uptakes were measured visually (four-point scale) and semi-quantitatively (maximum standardized uptake value). RESULTS: Compared with the control group, FDG uptake increased significantly from the ileum to the rectosigmoid colon in group A, from the transverse to the rectosigmoid colon in group B, and from the descending colon to the rectosigmoid colon in group C in both visual and semi quantitative analyses. CONCLUSIONS: Metformin discontinuation for <72 h is likely suboptimal for PET/CT image interpretation, especially with respect to the distal segments of the colon. PMID- 27392948 TI - Dynamic motor tracking is sensitive to subacute mTBI. AB - Effective screening for mild traumatic brain injury (mTBI) is critical to accurate diagnosis, intervention, and improving outcomes. However, detecting mTBI using conventional clinical techniques is difficult, time intensive, and subject to observer bias. We examine the use of a simple visuomotor tracking task as a screening tool for mTBI. Thirty participants, 16 with clinically diagnosed mTBI (mean time since injury: 36.4 +/- 20.9 days (95 % confidence interval); median = 20 days) were asked to squeeze a hand dynamometer and vary their grip force to match a visual, variable target force for 3 min. We found that controls outperformed individuals with mTBI; participants with mTBI moved with increased variability, as quantified by the standard deviation of the tracking error. We modeled participants' feedback response-how participants changed their grip force in response to errors in position and velocity-and used model parameters to classify mTBI with a sensitivity of 87 % and a specificity of 93 %, higher than several standard clinical scales. Our findings suggest that visuomotor tracking could be an effective supplement to conventional assessment tools to screen for mTBI and track mTBI symptoms during recovery. PMID- 27392949 TI - AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in human neuronal cell line SHSY5Y. AB - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a xenobiotic agent with high persistency that induces neurotoxic effects altering neurodevelopment and behavior. The molecular mechanisms and the signaling pathways involved in TCDD mediated neurotoxicity, together with the search of its molecular targets in neurons are under intense study. We have previously shown that high nanomolar concentrations of TCDD for incubation times of minutes induce apoptosis in SHSY5Y human neuroblastoma cells by the disruption of calcium homeostasis, affecting membrane structural integrity. In this work, we have analyzed the effect of low nanomolar concentrations of TCDD for incubation times of hours to define the role of aryl hydrocarbon receptor which can be activated at those concentrations. TCDD induces toxicity in SHSY5Y human neuroblastoma cells under these experimental conditions with an EC50 value of approximately 3nM at 24h of incubation time. Transient transfection of a hairpin RNA for AhR protects against TCDD neurotoxicity, suggesting that AhR is mediating the dioxin effect. Altogether, these results support the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma cells depends on dioxin concentration and time of incubation, with a main role of aryl hydrocarbon receptor at low nanomolar TCDD concentrations. PMID- 27392950 TI - The Chemistry of the Noncanonical Cyclic Dinucleotide 2'3'-cGAMP and Its Analogs. AB - The cyclic dinucleotides (CDNs) cyclic diguanosine monophosphate (c-diGMP) and cyclic diadenosine monophosphate (c-diAMP) with two canonical 3'->5' internucleotide linkages are ubiquitous second messenger molecules in bacteria, regulating a multitude of physiological processes. Recently the noncanonical CDN cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) featuring a mixed linkage, which consists of a 2'->5' and a 3'->5' internucleotide bond, has been identified as a signaling molecule in metazoan species in late 2012. 2'3' cGAMP formation is biocatalyzed by cGAMP synthase (cGAS) upon sensing of cytosolic double-stranded DNA (dsDNA) and functions as an endogenous inducer of innate immunity by directly binding to and activating the adaptor protein stimulator of interferon genes (STING). Thereby 2'3'-cGAMP can stimulate interferon-beta (INF-beta) secretion, a major signaling pathway of host defense, which is independent of toll-like receptor (TLR) activation. Medicinal chemistry of 2'3'-cGAMP and development of corresponding analogs are still in their infancy, and only a handful of structurally related compounds are available to the scientific community. The aim of this chapter is to summarize synthetic approaches to prepare canonical and noncanonical endogenous CDNs including 2'3' cGAMP. Furthermore, we will describe syntheses of 2'3'-cGAMP analogs bearing modifications, which will facilitate further studies of the emerging biological functions of 2'3'-cGAMP and to identify additional receptor proteins. Finally, we will review latest developments concerning 2'3'-cGAMP analogs with improved hydrolytic stability in cell cultures and in tissues, putatively qualifying for new therapeutic options on the basis of 2'3'-cGAMP signaling. PMID- 27392953 TI - Effect of Resveratrol Administration on the Element Metabolism in the Blood and Brain Tissues of Rats Subjected to Acute Swimming Exercise. AB - The aim of the present study is to examine how resveratrol administration affects the element metabolism in the blood and brain cortex tissues of rats subjected to an acute swimming exercise. The study was carried out on Wistar-Albino-type adult male rats supplied by the Center. Group 1 is the control group. Group 2 is the swimming control group. Group 3 is the resveratrol (10 mg/kg/day) + swimming group. Group 4 is the resveratrol (10 mg/kg/day) group. Blood and brain cortex tissues were analyzed for some elements. The acute swimming exercise led to increases in the rats' serum iron, selenium, lead, cobalt, and boron levels, while the resveratrol-swimming group has increases in copper, phosphorus, and calcium values. The brain cortex tissue of the resveratrol-swimming group had significantly higher molybdenum levels than others. The results obtained in the study indicate that acute swimming exercise altered the distribution of elements in the serum to a considerable extent; however, resveratrol's affect is limited. Especially, resveratrol supplementation may have a regulatory affect on serum iron and magnesium levels. PMID- 27392952 TI - ICO-OSCAR for pediatric cataract surgical skill assessment. AB - Pediatric cataract surgical skill assessment is important to ensure the competency of the trainees, especially pediatric ophthalmology fellows. Using a rubric would ensure objectivity in this process. The ICO-OSCAR pediatric cataract surgery rubric has been developed with global variations in techniques of pediatric cataract surgery in mind. PMID- 27392954 TI - Changes in Trace Element Contents and Morphology in Bones of Duck Exposed to Molybdenum or/and Cadmium. AB - Cadmium (Cd) and high molybdenum (Mo) can lead to adverse reactions on animals, but the coinduced toxicity of Mo and Cd to bone in ducks was not well understood. The objective of this study was to investigate the changes in trace elements' contents and morphology in bones of duck exposed to Mo or/and Cd. One hundred twenty healthy 11-day-old male ducks were randomly divided into six groups and treated with commercial diet containing Cd or/and Mo. On the 60th and 120th days, the blood, excretion, and metatarsals were collected to determine alkaline phosphatase (ALP) activity and the contents of Mo, Cd, calcium (Ca), phosphorus (P), copper (Cu), iron (Fe), zine (Zn), and selenium (Se). In addition, metatarsals were subjected to histopathological analysis with the optical microscope and radiography. The results indicated that Mo and Cd contents significantly increased while Ca, P, Cu, and Se contents remarkably decreased in metatarsals in coexposure groups (P < 0.01). Contents of Fe and Zn in metatarsals had no significant difference among groups (P > 0.05). Ca content in serum had no significant difference among experimental groups (P > 0.05), but P content was significantly decreased in HMo and HMo + Cd groups (P < 0.05). Contents of Ca and P in excretion and ALP activity were significantly increased in coinduced groups (P < 0.05). Furthermore, osteoporotic lesions, less and thinner trabecular bone were observed in combination groups. The findings suggested that dietary of Cd or/and Mo could lead to bone damages in ducks via disturbing the balance of Ca and P in body and homeostasis of Cu, Fe, Zn, and Se in bones; moreover, the two elements showed a possible synergistic relationship. PMID- 27392955 TI - Protective Effects of PGC-1alpha Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis Sertoli Cells. AB - The reproductive system is sensitive to lead (Pb) toxicity, which has long been an area of research interest, but the underlying mechanisms remain to be illustrated. Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is pivotal in mitochondrial function. In this study, mouse testis Sertoli cells (TM4 cells), PGC-1alpha lower-expression (PGC-1alpha(-)) TM4 cells and PGC-1alpha overexpression (PGC-1alpha(+)) TM4 cells were used to explore the protective roles of PGC-1alpha against lead toxicity on the mouse reproductive system. Lead acetate (PbAc) exposure decreased the expression level of PGC 1alpha, increased the intracellular level of reactive oxygen species (ROS), and reduced the level of ATP in the three TM4 cell lines. The effects of PbAc on intracellular ATP level and on ROS content were significantly weakened in PGC 1alpha(+)TM4 cells versus TM4 cells and were significantly amplified in PGC 1alpha(-)TM4 cells versus TM4 cells. These results suggest that PGC-1alpha is a protective factor against PbAc-induced oxidative stress and energy metabolism dysfunction in the mouse reproductive system, thereby holding the potential of being developed as a preventive or therapeutic strategy against disorders induced by lead exposure. PMID- 27392951 TI - Role of C-Jun N-terminal Kinase in Hepatocellular Carcinoma Development. AB - Hepatocellular carcinoma (HCC) is among the most frequently occurring cancers and the leading causes of cancer mortality worldwide. Identification of the signaling pathways regulating liver carcinogenesis is critical for developing novel chemoprevention and targeted therapies. C-Jun N-terminal kinase (JNK) is a member of a larger group of serine/threonine (Ser/Thr) protein kinases known as the mitogen-activated protein kinase (MAPK) family. JNK is an important signaling component that converts external stimuli into a wide range of cellular responses, including cell proliferation, differentiation, survival, migration, invasion, and apoptosis, as well as the development of inflammation, fibrosis, cancer growth, and metabolic diseases. Because of the essential roles of JNK in these cellular functions, deregulated JNK is often found to contribute to the development of HCC. Recently, the functions and molecular mechanisms of JNK in HCC development have been addressed using mouse models and human HCC cell lines. Furthermore, recent studies demonstrate that the activation of JNK by oncogenes can promote the development of cancers by regulating the transforming growth factor (TGF) beta/Smad pathway, which makes the oncogenes/JNK/Smad signaling pathway an attractive target for cancer therapy. Additionally, JNK-targeted therapy has a broad potential for clinical applications. In summary, we are convinced that promising new avenues for the treatment of HCC by targeting JNK are on the horizon, which will undoubtedly lead to better, more effective, and faster therapies in the years to come. PMID- 27392957 TI - In reply to letter to the editor from Dr. Kawada regarding the publication "Dairy product consumption and risk of type 2 diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk". PMID- 27392956 TI - Species-specific diagnostics of Apis mellifera trypanosomatids: A nine-year survey (2007-2015) for trypanosomatids and microsporidians in Serbian honey bees. AB - In this study, honey bees collected in Serbia over 9 consecutive years (2007 2015) were retrospectively surveyed to determine the prevalence of eukaryotic gut parasites by molecular screening of archival DNA samples. We developed species specific primers for PCR to detect the two known honey bee trypanosomatid species, Crithidia mellificae and the recently described Lotmaria passim. These primers were validated for target specificity under single and mixed-species conditions as well as against the bumblebee trypanosomatid Crithidia bombi. Infections by Nosema apis and Nosema ceranae (Microsporidia) were also determined using PCR. Samples from 162 colonies (18 from each year) originating from 57 different localities were surveyed. L. passim was detected in every year with an overall frequency of 62.3% and annual frequencies ranging from 38.9% to 83.3%. This provides the earliest confirmed record to date for L. passim and the first report of this species in Serbia. N. ceranae was ubiquitous, occurring in every year and at 95.7% overall frequency, ranging annually from 83.3% to 100%. The majority of colonies (60.5%) were co-infected with L. passim and N. ceranae, but colony infections by each species were statistically independent of one another over the nine years. Although C. mellificae and N. apis have both been reported recently at low frequency in Europe, neither of these species was detected in Serbia. These results support the hypothesis that L. passim has predominated over C. mellificae in A. mellifera during the past decade. PMID- 27392958 TI - FSGS: from pathogenesis to the histological lesion. AB - Focal and segmental glomerulosclerosis (FSGS) is a generic term that in the current terminology can be appropriate for identifying two conditions. First, a morphological pattern of injury characterized by the occlusion of a single or group of glomerular capillary loops by sclerotic material, indicating a precise histological lesion but with a wide range of etiological interpretations. Second, a pauci-immune renal disease called idiopathic or primary FSGS, which is a podocytopathy triggered by an endogenous cytotoxin that recognizes the podocyte as its sole target. Based on the current and past literature, we do not possess practical tools to easily provide a precise classification of an FSGS lesion, although some clues may be of help in everyday clinical practice. Reactive forms, genetic forms, adaptive forms, forms associated with a deregulation of the proliferation and forms secondary to local glomerular inflammation are the etiological classes known to be associated with the development of an FSGS lesion. However, diagnosing each single case based on clinical, serological and histological criteria is still far from easy and mostly depends on the experience of the renal team, which should involve skilled nephrologists and pathologists. PMID- 27392959 TI - Early markers for myocardial ischemia and sudden cardiac death. AB - The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (<=30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (<=1 h), myoglobin (<=1 h), troponins I and T (<=1 h), TUNEL (<=1 h), and C5b-9 (<=2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB. PMID- 27392962 TI - [Not Available]. PMID- 27392960 TI - Pomological Traits, Sensory Profile and Nutraceutical Properties of Nine Cultivars of Loquat (Eriobotrya japonica Lindl.) Fruits Grown in Mediterranean Area. AB - In this paper the diversity of fruit quality within nine loquat cultivars, including five international affirmed cultivars (Algerie, Golden Nugget, Peluche, Bueno, El Buenet) and four local cultivars (Sanfilippara, Nespolone di Trabia, BRT20 and Claudia), were investigated in order to discriminate the variation in pomological characteristics, sensory profile, and antioxidant properties. Finally, to evaluate potential bioactivity, antiproliferative activity of hydrophilic extracts from loquat fruits was assessed, at dietary relevant concentrations, against three human epithelial cell lines. Even though the international cultivars confirmed an appropriate level of commercial qualities in association to high levels in antioxidant compounds, the local cultivars revealed the best performances in a wide range of chemical-physical and sensory characteristics. Concerning bioactivity, our results indicate that hydrophilic extracts from all tested cultivars showed concentration-dependent antiproliferative activity with a significant variability of effects between different cell lines and between different cultivars. HeLa cells, the most sensitive and hydrophilic extracts from Peluche, showed the highest inhibitory effect followed by Nespolone di Trabia and Claudia. The results of this trial provide useful information on the pomological traits and the not yet known specific nutritional and functional properties of loquat fruits. Our data, besides helping to promote specific local cultivars, could serve to establish a database that will permit to improve the utilization of specific genetic resources in breeding programs. PMID- 27392963 TI - [Not Available]. PMID- 27392961 TI - Three-Step Test System for the Identification of Novel GABAA Receptor Modulating Food Plants. AB - Potentiation of gamma-amino butyric acid (GABA)-induced GABAA receptor (GABAAR) activation is a common pathway to achieve sedative, sleep-enhancing, anxiolytic, and antidepressant effects. Presently, a three-component test system was established for the identification of novel GABAAR modulating food plants. In the first step, potentiation of GABA-induced response of the GABAAR was analysed by two-electrode voltage clamp (TEVC) for activity on human alpha1beta2-GABAAR expressed in Xenopus laevis oocytes. Positively tested food plants were then subjected to quantification of GABA content by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) to exclude test foods, which evoke a TEVC-response by endogenous GABA. In the third step, specificity of GABAA-modulating activity was assessed by TEVC analysis of Xenopus laevis oocytes expressing the homologous glycine receptor (GlyR). The three-component test was then applied to screen 10 aqueous extracts of food plants for their GABAAR activity. Thus, hop cones (Humulus lupulus) and Sideritis sipylea were identified as the most potent specific GABAAR modulators eliciting significant potentiation of the current by 182 +/- 27 and 172 +/- 19 %, respectively, at the lowest concentration of 0.5 MUg/mL. The extracts can now be further evaluated by in vivo studies and by structural evaluation of the active components. PMID- 27392965 TI - [Not Available]. PMID- 27392964 TI - [Not Available]. PMID- 27392966 TI - Sphingobium hydrophobicum sp. nov., a hydrophobic bacterium isolated from electronic-waste-contaminated sediment. AB - Four hydrophobic bacteria were isolated from sediment at Guiyu, an electronic waste recycling site in southeastern China. The isolates had high cell surface hydrophobicity with microbial-adhesion-to-hydrocarbon score of 71.4 %. 16S rRNA gene sequences of the strains all showed highest similarity to the hydrophilic Sphingobium xenophagum DSM 6383T (99.9 % 16S rRNA gene sequence similarity), followed by Sphingobiumczechense DSM 25410T (97.1 %). However, DNA-DNA hybridization revealed that the isolates and S. xenophagum DSM 6383T exhibited low DNA-DNA relatedness with a hybridization value of 54.5+/-0.5 %. The genomic DNA G+C content was 64.2 mol% and the predominant quinone was ubiquinone Q-10. Spermidine was the major polyamine component. The major fatty acids were C18 : 1omega7c, C16 : 1omega7c, C16 : 0, C14 : 0 2-OH and C14 : 0. In contrast to its closest relative S. xenophagum DSM 6383T, the isolates had a much higher proportion of C16 : 0 and C14 : 0 and a much lower proportion of C18 : 1omega9t. Sphingoglycolipid was present and diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylmonomethylethanolamine were detected in the polar lipid pattern. Phosphatidyldimethylethanolamine and phosphatidylcholine, which are present in S. xenophagum DSM 6383T, were not detected in the isolates. Results of DNA-DNA relatedness, cell surface hydrophobicity, fatty acids, polar lipids, and biochemical and physiological properties reveal that the isolates represent a novel species of the genus Sphingobium, for which the name Sphingobium hydrophobicum sp. nov. is proposed. The type strain is C1T (=CCTCC AB 2015198T=KCTC 42740T). PMID- 27392967 TI - Cost of Purchased Versus Produced Plasma from Donor Recruitment Through Transfusion. AB - BACKGROUND: Plasma is used to treat acquired coagulopathy or thrombotic thrombocytopenic purpura, or to reverse warfarin effect. Scant data are available, however, about its costs. OBJECTIVE: To estimate total costs of plasma from production through administration, from the perspective of a US hospital blood donor center (BDC). STUDY DESIGN AND METHODS: Six sequential decision analytic models were constructed and informed by primary and secondary data on time, tasks, personnel, and supplies for donation, processing, and administration. Expected values of the models were summed to yield the BDC's total cost of producing, preparing, and transfusing plasma. Costs ($US 2015) are reported for a typical patient using three units of plasma. Models assume plasma was obtained from whole blood donation and transfused in an inpatient setting. Univariate sensitivity analyses were performed to test the impact of changing inputs for personnel costs and adverse event (AE) rates and costs. RESULTS: BDC production cost of plasma was $91.24/patient ($30.41/unit), a $30.16/patient savings versus purchased plasma. Administration and monitoring costs totaled $194.64/patient. Sensitivity analyses indicated that modifying BDC personnel costs during donation and processing has little impact on total plasma costs. However, the probability and cost of transfusion-associated circulatory overload (TACO) have a significant impact on costs. CONCLUSION: Plasma produced by our BDC may be less costly than purchased plasma. Though plasma processes have multiple tasks involving staff time, these are not the largest cost driver. Major plasma related AEs are uncommon, but are the biggest driver of total plasma costs. PMID- 27392968 TI - Prevalence of hypervirulent Klebsiella pneumoniae-associated genes rmpA and magA in two tertiary hospitals in Houston, TX, USA. PMID- 27392969 TI - Inflammation Drives Retraction, Stiffening, and Nodule Formation via Cytoskeletal Machinery in a Three-Dimensional Culture Model of Aortic Stenosis. AB - In calcific aortic valve disease, the valve cusps undergo retraction, stiffening, and nodular calcification. The inflammatory cytokine, tumor necrosis factor (TNF) alpha, contributes to valve disease progression; however, the mechanisms of its actions on cusp retraction and stiffening are unclear. We investigated effects of TNF-alpha on murine aortic valvular interstitial cells (VICs) within three dimensional, free-floating, compliant, collagen hydrogels, simulating their natural substrate and biomechanics. TNF-alpha increased retraction (percentage of diameter), stiffness, and formation of macroscopic, nodular structures with calcification in the VIC-laden hydrogels. The effects of TNF-alpha were attenuated by blebbistatin inhibition of myosin II-mediated cytoskeletal contraction. Inhibition of actin polymerization with cytochalasin-D, but not inhibition of Rho kinase with Y27632, blocked TNF-alpha-induced retraction in three-dimensional VIC hydrogels, suggesting that actin stress fibers mediate TNF alpha-induced effects. In the hydrogels, inhibitors of NF-kappaB blocked TNF alpha-induced retraction, whereas simultaneous inhibition of c-Jun N-terminal kinase was required to block TNF-alpha-induced stiffness. TNF-alpha also significantly increased collagen deposition, as visualized by Masson's trichrome staining, and up-regulated mRNA expression of discoidin domain receptor tyrosine kinase 2, fibronectin, and alpha-smooth muscle actin. In human aortic valves, calcified cusps were stiffer and had more collagen deposition than noncalcified cusps. These findings suggest that inflammation, through stimulation of cytoskeletal contractile activity, may be responsible for valvular cusp retraction, stiffening, and formation of calcified nodules. PMID- 27392970 TI - Regulation of Collagen V Expression and Epithelial-Mesenchymal Transition by miR 185 and miR-186 during Idiopathic Pulmonary Fibrosis. AB - Idiopathic pulmonary fibrosis is a devastating disease, with no good diagnostic biomarker and limited treatment options. Previous studies suggest that collagen V overexpression and collagen V-mediated immune response play roles in the pathogenesis of idiopathic pulmonary fibrosis. This study aimed to identify dysregulated miRNA-related collagen V overexpression during idiopathic pulmonary fibrosis. We found that the expression levels of miR-185 and miR-186 were decreased in the lungs of idiopathic pulmonary fibrosis patients. The levels of miR-185 and miR-186 were not correlated with disease severity of idiopathic pulmonary fibrosis. The direct regulation of COL5A1 by miR-185 and miR-186 was confirmed by a luciferase reporter assay. Furthermore, mimics of miR-185 and miR 186 blocked transforming growth factor-beta-induced collagen V overexpression and alleviated transforming growth factor-beta-induced epithelial-mesenchymal transition in A549 cells and HCC827 cells. Our findings suggest that attenuated expression of miR-185 and miR-186 may be responsible for collagen V overexpression during idiopathic pulmonary fibrosis, and these miRNAs may serve as pathogenesis-related biomarkers and treatment targets. PMID- 27392973 TI - Letter to the Editor: Trocar Site Hernia Prevention in Laparoscopic Bariatric Surgery. PMID- 27392972 TI - Performance of the Bard Scoring System in Bariatric Surgery Patients with Nonalcoholic Fatty Liver Disease. AB - BACKGROUND: Nonalcoholic fatty liver disease incidence is related to the presence of obesity and insulin resistance. A treatment of this disease in patients with morbid obesity is bariatric surgery and its diagnosis is extremely important due to the possible progression to cirrhosis or hepatocellular carcinoma. The development of clinical-laboratorial analysis tools to this disease and its complications is necessary as the gold standard for its diagnosis is an invasive procedure. The objective of the study is to evaluate the use of BARD score in the selection of patients who should undergo liver biopsy during bariatric surgery. METHODS: It was a retrospective analysis of patients with hepatic disease who were biopsied between 2012 and 2013. Their clinical and laboratory data were analyzed by BARD score. The results of those who presented score >2 were compared to the rest. RESULTS: Two hundred ninety-eight patients with hepatic disease were analyzed and among them 70.27 % had score >2. Of the 76 patients with score <1, 1 was diagnosed with liver fibrosis, determining a negative predictive value of 98.68 % for the test (p < 0.05). CONCLUSIONS: The BARD score is still not ideal for the diagnosis of nonalcoholic fatty liver disease, hepatitis, and fibrosis, but it was proved to be effective in the detection of absence of liver fibrosis in a bariatric population. PMID- 27392971 TI - Impact of HIV-1 infection on the feto-maternal crosstalk and consequences for pregnancy outcome and infant health. AB - Adaptation of the maternal immune system to establish maternal/fetal equilibrium is required for a successful pregnancy. Viral infections, including HIV-1 infection, can alter this maternal/fetal equilibrium, with significant consequences for pregnancy outcome, including miscarriages, impaired fetal growth, and premature delivery. Furthermore, maternal HIV-1 infection has been shown to have a long-term impact on the developing fetal immune system also when the infant is not infected with the virus. In this review, we discuss the consequences of maternal HIV-1 infection and antiretroviral therapy on pregnancy outcome and the health of the uninfected HIV-1-exposed infant. PMID- 27392974 TI - Thioglycolic Acid-Capped CdS Quantum Dots Conjugated to alpha-Amylase as a Fluorescence Probe for Determination of Starch at Low Concentration. AB - In the present research, water soluble thioglycolic acid-capped CdS quantum dots (QDs) were synthesized by chemical precipitation method. The characteristics of prepared quantum dots were determined using X-Ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). The obtained results revealed that CdS QDs have 5.60 nm crystallite size, hexagonal wurtzite structure and spherical morphology with less than 10 nm diameter. The photoluminescence (PL) spectroscopy was performed in order to study the effect of the presence of starch solutions. Blue emission peaks were positioned at 488 nm and its intensity quenched by increasing the concentration of starch solutions. The result of PL quenches in range of studied concentrations (0-100 ppm) was best described by Michaelis Menten model. The amount of Michaelis constant (Km) for immobilized alpha-amylase in this system was about 68.08 ppm which showed a great tendency of enzyme to hydrolyze the starch as substrate. Finally, the limit of detection (LOD) was found to be about 2.24 ppm. PMID- 27392975 TI - Thiacalix[4]arene-tetra-(quinoline-8- sulfonate): a Sensitive and Selective Fluorescent Sensor for Co (II). AB - A novel fluorescent thiacalix[4]arene-tetra-(quinoline-8-sulfonate) (TCTQ8S) was synthesized by condensation of thiacalix[4]arene (TCA) and 8-quinoline sulfonyl chloride(8QSC). TCTQ8S was characterized by ESI-MS, (1)H-NMR and (13)C-NMR spectroscopic methods. TCTQ8S was found to be an efficient "turn-off" fluorescent sensor for the selective and sensitive recognition of Co(II) ions. The Job's plot measurement reveals a 1:1 stoichiometric ratio. The designed chemosensor exhibited high selectivity toward Co(II) ions vs. other tested metal ions, with a detection limit of up to 1.038 * 10(-9) M. The binding constant and quantum yield for the complex were also determined. Molecular docking studies have been successfully performed to support 1:1 binding of TCTQ8S with the Co(II) metal ion. TCTQ8S was evaluated for real sample analysis on water sample for the detection of Co(II). Graphical Abstract Thiacalix derivatized fluorescent sensor for the selective detection of Co(II). PMID- 27392977 TI - Relationship between healthcare worker surface contacts, care type and hand hygiene: an observational study in a single-bed hospital ward. AB - This study quantifies the relationship between hand hygiene and the frequency with which healthcare workers (HCWs) touch surfaces in patient rooms. Surface contacts and hand hygiene were recorded in a single-bed UK hospital ward for six care types. Surface contacts often formed non-random patterns, but hygiene before or after patient contact depends significantly on care type (P=0.001). The likelihood of hygiene correlated with the number of surface contacts (95% confidence interval 1.1-5.8, P=0.002), but not with time spent in the room. This highlights that a potential subconscious need for hand hygiene may have developed in HCWs, which may support and help focus future hygiene education programmes. PMID- 27392979 TI - [Not Available]. PMID- 27392978 TI - Carbapenem-resistant Enterobacteriaceae colonization and infection in critically ill patients: a retrospective matched cohort comparison with non-carriers. AB - OBJECTIVES: To examine whether carbapenem-resistant Enterobacteriaceae (CRE) carriage is associated with incidence of clinical infection as a means of assessing whether the morbidity and mortality associated with these bacteria are mediated by underlying conditions or intrinsic properties of CRE. METHODS: This retrospective matched cohort study compared the incidence of invasive infections in CRE-colonized patients and matched non-carriers in the intensive care unit (ICU). The primary outcome was infection caused by CRE of the same species as the colonizing strain among CRE carriers, and infections caused by carbapenem sensitive strains of the same organism in non-carriers. Hospital discharge and death were considered as competing events. Competing-risks hazard analysis was performed for the entire cohort and for a nested cohort matched by Acute Physiology and Chronic Health Evaluation (APACHE) II scores, stratified by matching. RESULTS: In total, 146 CRE carriers were compared with 292 non carriers. Patients were well matched for most risk factors for Enterobacteriaceae infection, including age, renal failure, previous invasive infection, previous hospitalization, APACHE II score, length of mechanical ventilation, length of hospitalization and CRE carriage. On regression analysis, colonization with CRE was independently associated with Enterobacteriaceae infection {cause-specific hazard ratio (CSHR) 2.06 [95% confidence interval (CI) 1.03-4.09]}. On regression analysis of the APACHE-II-matched cohort (N=284), colonization with CRE remained significantly associated with Enterobacteriaceae infection [CSHR 3.32 (95% CI 1.31-8.43)]. CONCLUSIONS: Colonization with CRE was associated with at least a two-fold increased risk of infection by the colonizing strain amongst ICU patients. PMID- 27392980 TI - [Not Available]. AB - Cisplatin is an anticancer agent widely used in clinical practice. Cisplatin undergoes irreversible protein binding in plasma and presents a major nephrotoxicity. Some studies determined unbound and bound platin concentrations using flameless atomic absorption spectrophotometry or chromatography. These studies showed a relationship between cisplatin exposition, notably its maximal concentration, and nephrotoxicity. However, the relationship between cisplatin exposition and its efficacy is not yet established. The population approach using a nonlinear mixed effects model showed a low variability of drug exposition parameters. In some cases, Bayesian adaptative dosing were proposed. However, some particular populations will have to be taken into account such as children, elderly patients, acute or chronic renal failure. The impact of cisplatin pharmacogenetics on its therapeutic monitoring need to be studied. Therapeutic cisplatin monitoring is today possibly useful measuring maximal concentration and using described ajusted-modelling. Some prospective multicentric validations are required. PMID- 27392981 TI - [Not Available]. AB - Carboplatin is an anticancer agent widely used in different types of cancer in adults and paediatrics patients. Carboplatin undergoes an high protein binding percentage in plasma and presents a major hematotoxicity. Some studies determined unbound and bound platin concentrations using flameless atomic absorption spectrophotometry or chromatography. These studies showed a relationship between carboplatin exposition expressed using AUC of ultrafiltrable concentrations with time and myelotoxicity. However, the relationship between carboplatin exposition and its efficacy is not yet established. The population approach using a nonlinear mixed effects model showed a low variability of drug exposition parameters. In some cases, Bayesian adaptative dosing were proposed. However, some particular populations will have to be taken into account such as intensive doses of carboplatin, children, patients with hemodialysis-dependant renal insufficiency or obese patients. Therapeutic carboplatin monitoring is today recommended measuring AUC ultrafiltrable concentrations in time and using described ajusted-modelling. PMID- 27392982 TI - [Not Available]. AB - After HDMTX infusions, i.e. at a dose >1g/m(2), monitoring of serum MTX concentrations is a standard practice which helps reducing the incidence of toxicity in patients with decreased clearance by guiding dose adjustment of leucovorin. Therapeutic monitoring of methotrexate is based on iterative measurements of serum concentration until concentration is below a certain threshold. This practice is supported by numerous observations of exposure related toxicity as well as some clinical studies comparing drug exposure between patients with and without toxicity. Despite no prospective clinical study has clearly demonstrated the usefulness of methotrexate TDM, historical comparison reveals a huge reduction of toxicity-related events over past decades. Systematic monitoring may also help identifying patients with abnormally high methotrexate concentrations, who require immediate treatment with carboxypeptidase. PMID- 27392983 TI - [Not Available]. AB - Therapeutic drug monitoring is currently investigated in patients receiving the drug by prolonged continuous infusion, either alone or associated with other chemotherapy agents. This arises from an increasing body of evidence that relates plasma fluorouracil concentrations to toxicity or effectiveness. Literature data indicate that threshold levels of exposure, as assessed by the area under the concentration-time curve, are associated with an increased risk of toxicity in patients treated for either a colorectal or a head and neck cancer. Kinetically guided dose adjustment may thus be proposed for the ongoing or the next cycle of chemotherapy. Historical comparisons and the results of a phase III multicenter randomized study in patients with metastatic colorectal cancer showed that dose adapted fluorouracil resulted in significantly improved objective response rate, a trend to higher survival rate and fewer grade III-IV toxicities. Real-time fluorouracil monitoring may also help identifying patients with higher than expected exposure, thus providing a basis for intensifying supportive care in these patients. PMID- 27392984 TI - [Not Available]. AB - Azathioprine, 6-mercaptopurine, and 6-thioguanine are immunosuppressive drugs indicated in the prevention of graft rejection, and treatment of auto-immune disease or inflammatory bowel disease. Their anti-nucleotidic properties are also used for the treatment of acute leukaemia. Their metabolism involves thiopurine methyl transferase, which activity varies according to genetic polymorphisms. In inflammatory bowel disease patients, there is no recommended therapeutic range of intra-erythrocyte 6-thioguanine nucleotide concentration, the active metabolite. Therapeutic drug monitoring of 6-thioguanine nucleotide concentrations is however proposed in the following clinical situations: to check the observance, to try to explain therapeutic failure, to manage patients with limited thiopurine methyl transferase activity or patients treated with associated drugs that can modify thiopurine methyl transferase activity. The literature review shows that high concentrations of 6-thioguanine nucleotides and methylated metabolites are associated with an increased risk of bone marrow toxicity. In addition, high concentrations of methylated metabolite might increase the risk of hepatic toxicity. These major side-effects can be prevented by the use of pre-treatment screening for thiopurine methyl transferase activity or genotype in inflammatory bowel disease patients in order to propose an adapted dosing. PMID- 27392985 TI - [Not Available]. AB - 6-mercaptopurine, a key drug for the treatment of acute lymphoblastic leukaemia in children, is a prodrug metabolized into 6-thioguanine (6-TGN) which are the active compounds and into methylated metabolites, primary by thiopurine S methyltransferase enzyme (TPMT). This enzyme displays important inter subject variability linked to a genetic polymorphism: when treated with standard doses of thiopurine, TPMT-deficient and heterozygous patients are at great risk for developing severe and potentially life-threatening toxicity (hematopoietic, hepatic, mucositis. . . ) but show a better survival rate while patients with high TPMT activity (wild type) present lower peripheral red blood cells 6-TGN concentrations and a higher risk of leukemia relapse. Genotyping remains crucial before 6-MP administration at diagnosis to identify patients with homozygous mutant TPMT genotype and therefore prevent severe and life-threatening toxicity, and to individualize therapy according to TMPT genotype. Follow-up of ALL treatment should preferentially be based on repeated determinations of intracellular active metabolites (6-thioguanine nucleotides) and methylated metabolites in addition to haematological surveillance. PMID- 27392986 TI - [Not Available]. AB - Paclitaxel is an anticancer drug which displays pharmacokinetic properties which can lead to therapeutic drug monitoring requirement. The most effective pharmacokinetic parameter seems to be the time during the plasma concentration is over 0.05 MUmol/L. However, this target needs to be validated with new weekly schedules of administration. These reasons lead to consider the level of evidence of therapeutic drug monitoring of paclitaxel as potentially useful. PMID- 27392987 TI - [Not Available]. AB - Pharmacokinetic properties of docetaxel, an anticancer drug, are though to be interesting for therapeutic drug monitoring: high inter- and intra-variability, relationship between exposure and efficacy and especially toxicity. Moreover, the 3-weekly administration, which is the more effective scheme, is also the more toxic. However, neutropenia can be modelised and be efficiently predicted without needing plasma drug concentrations. The level evidence of therapeutic drug monitoring is thus weak regarding the possibility to adapt dose regimen without drug concentrations. PMID- 27392988 TI - [Not Available]. AB - Oral etoposide displays high inter- and intra-variability. Convincing relationships were observed between hematological toxicities and exposure of which total etoposide area under the curve seems the more relevant in routine practice. Linear pharmacokinetics, limited sampling strategies and reduction of variability during concentration-controlled studies argue in favor of therapeutic drug monitoring. For these reasons, such practice can be considered as recommended or potentially useful. Further studies using Bayesian approach are nevertheless needed to definitely state regarding the level of evidence therapeutic drug monitoring of oral etoposide. PMID- 27392989 TI - [Not Available]. AB - During the last decade, imatinib was current gold standard treatment of chronic myelogenous leukemia (CML), showing a great effectiveness. Thus, the Therapeutic Drug Monitoring (TDM), rarely applied in clinical oncology practice, did not appear necessary at the moment. However, the absence of response among patients and the metabolic profile of imatinib (involving the CYP3A4) suggested the existence of a great interindividual variability. During the last 4 years, studies about the pharmacokinetic/pharmacodynamic relationship have confirmed this variability and highlighted a relation between the trough concentrations of imatinib and the clinical response. An effectiveness threshold, close to 1000 ng/mL, seems to be correlated with better cytogenetic and molecular responses. Consequently, TDM could assist in investigation of the observance, the absence of response, the drug-drug interactions, but the proof of its utility requires complementary studies. In conclusion, the level of proof of imatinib TDM in LMC varies between levels "recommended" and "potentially useful". PMID- 27392990 TI - [Not Available]. AB - Clonazepam is a 1-4 benzodiazepine mainly used to treat epilepsy and epileptiform convulsion state. Rapidly absorbed after oral administration, it is widely distributed in the organism and is extensively converted in metabolites, poorly or not active, eliminated mainly in urine (70%) and feces. Elimination half-life is long, around 40 h. In adult and child, several studies showed a concentration effect relation. Meanwhile, a large inter-individual variability in the dose concentration relation was observed. A 15-50 MUg/L range of clonazepam blood concentrations appears to be retained as an acceptable target to control a majority of epileptic seizures. The Therapeutic Drug Monitoring (TDM) of clonazepam can be considered as possibly useful in case of association with CYP450 inducers or inhibitors, suspicion of poor observance, or toxicity signs. PMID- 27392991 TI - [Not Available]. AB - Clobazam is a 1,5 benzodiazepine available in France since 1975, used in add-on with the other anticonvulsant drugs in the treatment of refractory epilepsies of child and adult and for the treatment of anxiety of adult. It is mainly metabolized in desmethylclobazam, or norclobazam, active metabolite, present in a concentration approximately eight times superior to that of the parent drug, but with an activity of the order of 20 to 40% of that of clobazam. Elimination half life of clobazam is of 18 h while that of norclobazam is from 40 to 50 h. There is a large interindividual variability in the plasma concentrations. Furthermore, clobazam being prescribed in add-on with the other anticonvulsant drugs in resistant epilepsies, concentration-effect relationship is difficult to bring to light, since, in many studies, the patients who did not answer received the highest doses. Adverse reactions are moderated, appearing more often for the highest concentrations; also the phenomenon of tolerance seems more frequent in high concentrations. However, because of the kinetic interactions, a dosage of clobazam and norclobazam can be useful in certain cases. There is no validated therapeutic range, but the usual concentrations are in the range of 100-300 MUg/L for the parent drug and about ten times more for the metabolite. The level of proof of the interest of the Therapeutic Drug Monitoring for this molecule is estimated in: rather useless. PMID- 27392992 TI - [Not Available]. AB - Valproic acid is an anticonvulsant drug available in France since 1967. It is a broad spectrum molecule indicated in various forms of epilepsy of the adult and the child, but it is also prescribed in the treatment of different other pathologies of nervous system. The divalproate sodium is indicated in the treatment of bipolar disorders. The valproic acid is marketed under various pharmaceutical forms, with different corresponding tmax values. But, whatever the administered preparation, the circulating active molecule is the ion valproate. Elimination half-life is from 11 to 20 h. Metabolization of valproate is important and represents its main route of elimination. Valpromide is comparable to a prodrug which metabolizes in valproate. The inter and intraindividual variability of the plasma concentrations are important. Several studies show a concentration-effect relationship, but two interventional trials ended in the lack of interest of the Therapeutic Drug Monitoring (TDM), although it is of current practice. However, numerous drug interactions may modify the plasma concentrations of valproate. The therapeutic range is from 50 to 100 mg/L (346 - 693 MUmol/L). The level of proof of the interest of the TDM for this molecule was estimated in: recommended. PMID- 27392993 TI - [Not Available]. PMID- 27392994 TI - Association of ADIPOQ, LEP, and FTO gene polymorphisms with large for gestational age infants. AB - OBJECTIVE: The main objective of this study was to evaluate the effect of the ADIPOQ rs2241766, LEP rs7799039, and FTO rs9939609 polymorphisms on the birth weight status of Brazilian infants. METHODS: This cross-sectional study was conducted in southern Brazil. Large for gestational age (LGA) newborns (n = 105), and the same number of small for gestational age/adequate for gestational age newborns, were included. Genotyping of the rs2241766, rs7799039, and rs9939609 polymorphisms was done by PCR-RFLP analysis. Logistic regression was used to investigate the association between LGA newborns and the presence of the polymorphisms. RESULTS: Infants carrying the GG genotype of the rs7799039 polymorphism were 2.12 times more likely to be born LGA than those carrying the GA + AA genotypes (95% CI: 1.17-3.83). These results did not change substantially after adjusting for potential confounding variables (OR = 1.98; 95% CI 1.05-3.73) and adjustment for the three polymorphisms (OR = 1.98; 95% CI 1.05-3.74). Regarding the ADIPOQ polymorphism, newborns carrying the TG or GG genotype were 1.88 times more likely to be born LGA than those carrying the TT genotype, although this difference was not statistically significant (p = 0.082). No association was found between the FTO gene polymorphism and newborn weight status. CONCLUSIONS: This study showed that the GG genotype of the LEP polymorphism rs7799039 is a risk factor for LGA infants. The exact role and mechanism of action of the GG genotype of this polymorphism in weight status control remain to be elucidated, and more studies are needed. PMID- 27392995 TI - High HIV-1 Diversity and Prevalence of Transmitted Drug Resistance Among Antiretroviral-Naive HIV-Infected Pregnant Women from Rio de Janeiro, Brazil. AB - Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring. PMID- 27392996 TI - [Not Available]. AB - OBJECTIVES: High dose methotrexate (HD-MTX) may cause nonhaematological and haematological toxicities. MTX overexposure may be subsequent to administration errors or to delayed renal elimination resulting from MTX nephrotoxicity. The rescue agent carboxypeptidase rapidly hydrolyses MTX to inactive metabolites. However, current criteria for carboxypeptidase use are not well defined. We retrospectively evaluated the number of patients how should have received the drug if the criteria were applied, but who didn't receive it, and analysed their toxicities. METHODS: Patients treated at our institution in 2004 and 2005 and presenting the following criteria: concentrations of MTX at H48 >= 3 MUM, or impaired renal function, were considered. Post-course tolerance was recorded and graded. Recovery of renal function was followed-up periodically up to the 3rd month following the end of treatment. RESULTS: Twenty courses over 301 (7%) and 18 patients over 120 exhibited at least one criterion. Grade 3-4 toxicity was observed in 30% of the courses, including 2 severe acute renal impairment. Renal function decreased in most patients but had recovered upon the 3rd month in all but 2 patients. CONCLUSION: Despite a higher rate of toxicity than in general population, most of the patients recovered from it. Considering the cost of this treatment, the criteria for its therapeutic use could be restricted to concentration of MTX at H48 superior at 10| M, associated with renal impairment. PMID- 27392998 TI - [Not Available]. PMID- 27392997 TI - [Not Available]. AB - Local Bacillus Calmette-Guerin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcinoma. Local side effects are frequent, whereas systemic side effects are rare, but more serious. We report four cases of systemic BCG reaction. Although uncommon, this infectious complication of BCG therapy should always be considered in the appropriate clinical setting. The best approach to minimize this complication is a strict compliance with precautions and a close and rigorous surveillance of this drug. PMID- 27392999 TI - Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing? AB - HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10-14 yr on background hepatitis B-related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six-yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6-15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B-related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow-up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever-increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated. PMID- 27393000 TI - Stone-Mode Ultrasound for Determining Renal Stone Size. AB - PURPOSE: The purpose of this study was to measure the accuracy of stone-specific algorithms (S-mode) and the posterior acoustic shadow for determining kidney stone size with ultrasound (US) in vivo. MATERIALS AND METHODS: Thirty-four subjects with 115 renal stones were prospectively recruited and scanned with S mode on a research US system. S-mode is gray-scale US adjusted to enhanced stone contrast and resolution by minimizing compression and averaging, and increasing line density and frequency. Stone and shadow width were compared with a recent CT scan and, in 5 subjects with 18 stones, S-mode was compared with a clinical US system. RESULTS: Overall, 84% of stones identified on CT were detected on S-mode and 66% of these shadowed. Seventy-three percent of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT. A posterior acoustic shadow was present in 89% of stones over 5 mm versus 53% of stones under 5 mm. S-mode visualized 78% of stones, versus 61% for the clinical system. S-mode stone and shadow measurements differed from CT by 1.6 +/- 1.0 mm and 0.8 +/- 0.6 mm, respectively, compared with 2.0 +/- 1.5 mm and 1.6 +/- 1.0 mm for the clinical system. CONCLUSIONS: S-mode offers improved visualization and sizing of renal stones. With S-mode, sizing of the stone itself and the posterior acoustic shadow were similarly accurate. Stones that do not shadow are most likely <5 mm and small enough to pass spontaneously. PMID- 27393001 TI - The genetic background influences the cellular and humoral immune responses to vaccines. AB - The assessment of Toll-like receptor (TLR) agonists as candidate adjuvants for induction of effective T helper type 1 (Th1) immunity continues to rely on the use of mice. However, the genetic variation among inbred mice may influence the efficacy of adjuvants and bias a study's conclusions. Here, we evaluated the differences in cellular and humoral responses of genetically non-identical mouse strains immunized with ovalbumin (OVA) plus alum, TLR-3, TLR-4, TLR-7/8 or TLR-9 agonists. We found that all the tested TLR agonists recruited dendritic cells (DCs) and natural killer (NK) cells significantly into the lymph nodes, promoted DC-NK cross-talk and enhanced the cellular responses in B6 strain. In contrast, TLR-3 and TLR-7/8 were the only two agonists that showed the cellular adjuvanticity in the BALB/c strain. Compared with other TLR agonists, TLR-3 and TLR-7/8 were demonstrated to be the most effective adjuvants to generate interferon (IFN)-gamma-producing effector NK, CD4, and CD8 T cells in B6 and BALB/c strains, respectively. We also found that compared with alum, all adjuvants induced the recruitment of B cells and production of OVA-specific immunoglobulin (Ig)G2a more effectively in both strains. In addition, the B6 strain recruited more B cells, but surprisingly produced significantly lower amounts of OVA-specific IgG2a in response to all adjuvants. However, consistent with the frequency of IFN-gamma-producing effector cells observed in individual strains following immunizations, we detected more OVA-specific IgG2a in serum of B6 and BALB/c strains in response to TLR-3 and TLR-7/8, respectively. Our data suggest that genetic background should be taken into consideration when evaluating the activities of TLR agonists for the development of prophylactic and therapeutic vaccines. PMID- 27393002 TI - Association of Serum Thyrotropin with Anthropometric Markers of Obesity in the General Population. AB - BACKGROUND: Except from associations study with body weight, there are few longitudinal data regarding the association between thyroid function and anthropometric measurements such as waist circumference, waist-to-hip ratio, or waist-to height ratio. OBJECTIVE: This study aimed to investigate the association of thyrotropin (TSH) at baseline with changes in different anthropometric markers between baseline and follow-up in the general population. METHOD: Data were used from four population-based longitudinal cohort studies and one population-based cross-sectional study. A total of 16,902 (8204 males) subjects aged 20-95 years from the general population were studied. Body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio were measured. Multivariable median regression models were calculated adjusting for the following covariates: age, sex, baseline value of the respective anthropometric marker, smoking status, follow-up-time period, and study site. RESULTS: In cross-sectional analyses, serum TSH within the reference range was positively associated with waist circumference (beta = 0.94 cm [confidence interval (CI) 0.56-1.32]) and waist-to height-ratio (beta = 0.029 [CI 0.017-0.042]). These associations were also present for the full range of TSH. In the longitudinal analyses, serum TSH at baseline was inversely associated with a five-year change of all considered anthropometric measures within the prior defined study-specific reference range, as well as in the full range of serum TSH. CONCLUSION: High TSH serum levels were positively associated with current anthropometric markers, even in the study specific reference ranges. In contrast, high TSH serum levels were associated with decreased anthropometric markers over a time span of approximately five years. Further research is needed to determine possible clinical implications as well as public health consequences of these findings. PMID- 27393003 TI - Mitochondrial Peroxiredoxin-3 protects against hyperglycemia induced myocardial damage in Diabetic cardiomyopathy. AB - Mitochondrial oxidative stress has emerged as a key contributor towards the development of diabetic cardiomyopathy. Peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, scavenges H2O2 and offers protection against ROS related pathologies. We observed a decrease in the expression of Prx-3 in the hearts of streptozotocin (STZ) induced diabetic rats, and also high glucose treated H9c2 cardiac cells, which may augment oxidative stress mediated damage. Hence we hypothesized that overexpression of Prx-3 could prevent the cardiac damage associated with diabetes. In this study we used quercetin (QUE) to achieve Prx-3 induction in vivo, while a Prx-3 overexpressing H9c2 cell line was employed for carrying out in vitro studies. Diabetes was induced in Wistar rats by a single intraperitoneal injection of STZ. Quercetin (50mg/kg body weight) was delivered orally to hyperglycemic and age matched control rats for 2 months. Quercetin treatment induced the myocardial expression of Prx-3 but not Prx-5 both in control and STZ rats. Prx-3 induction by quercetin prevented diabetes induced oxidative stress as confirmed by decrease in expression of markers such as 4-HNE and mitochondrial uncoupling protein, UCP-3. It was also successful in reducing cardiac cell apoptosis, hypertrophy and fibrosis leading to amelioration of cardiac contractility defects. Overexpression of Prx-3 in cultured H9c2 cardiac cells could significantly diminish high glucose inflicted mitochondrial oxidative damage and apoptosis, thus strengthening our hypothesis. These results suggest that diabetes induced cardiomyopathy can be prevented by elevating Prx-3 levels thereby providing extensive protection to the diabetic heart. PMID- 27393005 TI - Muscle dysfunction in type 2 diabetes: a major threat to patient's mobility and independence. AB - Type 2 diabetes, a common metabolic disease in older people, is a major risk factor for functional limitation, impaired mobility, and loss of independence. In older people, the pathogenesis of functional limitation and disability is complex and multifactorial. A number of potential pathways are involved including cardiovascular disease, peripheral neuropathy, overweight, osteoarthritis, visual deficit, and cognitive impairment, conditions that are all more prevalent among patients with diabetes. Sarcopenia, a geriatric condition characterized by a progressive and generalized loss of skeletal muscle mass and strength, is also involved in the pathogenesis of functional limitations and disability. Recent research has shown that older patients with type 2 diabetes are often affected by skeletal muscle impairment, leading to reduced muscle strength and physical function. Insulin resistance, hyperglycemia, muscle fat infiltration, and peripheral neuropathies are hypothesized as the fundamental biological mechanisms leading to muscle impairment in people with diabetes. This review summarizes the current literature on the biological pathways responsible for skeletal muscle dysfunction in type 2 diabetes and analyzes the role of decline in muscle strength and quality on the association between diabetes and mobility disability. PMID- 27393004 TI - Redox signaling: An evolution from free radicals to aging. AB - Redox biology has evolved from studies of the pathology that involves oxidants to an understanding of how oxidants participate in normal as well as aberrant signal transduction. Although the concept that signal transduction involved changes in the redox state dates from the 1930s, the modern history of redox biology began with the discovery of superoxide dismutase by McCord and Fridovich. The initial focus was on free radicals and damage of macromolecules, which remains an important topic. But, over time it was realized that hydroperoxides, especially H2O2 produced by NADPH oxidases, and electrophiles derived from lipid peroxidation or metabolism, played essential roles in physiologically relevant signaling. The mechanisms through which H2O2 and other electrophiles signal became an important area of study that provided insight into how these reactive molecules were involved in major signaling pathways and regulation of transcription factors. Thus, the field of redox signaling that is the overlap of signal transduction with redox biology was established. Alterations in redox signaling are observed in aging, but we also now know that redox signaling is essential in physiological homeostasis and that sustained deviation from redox homeostasis results in disease. This is a review of the history of redox biology from a personal perspective of nearly fifty years working in this field that hopefully provides some insights for the reader. PMID- 27393006 TI - The ZJU index: a useful indicator for recognizing insulin resistance in the Chinese general population. AB - AIMS: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and is closely associated with insulin resistance (IR). The ZJU index is based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG) and the serum alanine aminotransferase-to-aspartate transaminase ratio, and is proven to be a novel and effective parameter for screening NAFLD in the Chinese population. We aimed to analyze the relationship between the ZJU index and IR. METHODS: A cross-sectional study of 3329 Chinese adults was performed. Blood pressure (BP), anthropometric measurements and biochemical parameters were tested. The BMI, ZJU index and homeostasis model assessment of IR (HOMA-IR) were calculated. RESULTS: In both genders, BP, waist circumference, BMI, total cholesterol, TG, low-density lipoprotein cholesterol levels, FPG, postprandial glucose levels, fasting insulin and the HOMA-IR gradually increased, while the HDL-C decreased across the quartiles of the ZJU index (P < 0.001). The logistic regression analysis showed that the risk of IR was significantly elevated in the highest quartile of the ZJU index. Additionally, the area under the receiver operating characteristic curve of the ZJU index was 0.833 (95 % CI 0.809-0.858) in males and 0.788 (95 % CI 0.758 0.818) in females and was relatively higher than other common variables. CONCLUSIONS: The ZJU index is a useful indicator for recognizing IR in the Chinese general population. PMID- 27393008 TI - Can Reduced-Step Polishers Be as Effective as Multiple-Step Polishers in Enhancing Surface Smoothness? AB - OBJECTIVES: The aim of this study was to evaluate the effects of various finishing and polishing systems on the final surface roughness of a resin composite. Hypotheses tested were: (1) reduced-step polishing systems are as effective as multiple-step systems on reducing the surface roughness of a resin composite and (2) the number of application steps in an F/P system has no effect on reducing surface roughness. MATERIALS AND METHODS: Ninety discs of a nano hybrid resin composite were fabricated and divided into nine groups (n = 10). Except the control, all of the specimens were roughened prior to be polished by: Enamel Plus Shiny, Venus Supra, One-gloss, Sof-Lex Wheels, Super-Snap, Enhance/PoGo, Clearfil Twist Dia, and rubber cups. The surface roughness was measured and the surfaces were examined under scanning electron microscope. Results were analyzed with analysis of variance and Holm-Sidak's multiple comparisons test (p < 0.05). RESULTS: Significant differences were found among the surface roughness of all groups (p < 0.05). The smoothest surfaces were obtained under Mylar strips and the results were not different than Super-Snap, Enhance/PoGo, and Sof-Lex Spiral Wheels. The group that showed the roughest surface was the rubber cup group and these results were similar to those of the One-gloss, Enamel Plus Shiny, and Venus Supra groups. CONCLUSIONS: (1) The number of application steps has no effect on the performance of F/P systems. (2) Reduced step polishers used after a finisher can be preferable to multiple-step systems when used on nanohybrid resin composites. (3) The effect of F/P systems on surface roughness seems to be material-dependent rather than instrument- or system-dependent. CLINICAL SIGNIFICANCE: Reduced-step systems used after a prepolisher can be an acceptable alternative to multiple-step systems on enhancing the surface smoothness of a nanohybrid composite; however, their effectiveness depends on the materials' properties. (J Esthet Restor Dent 29:31 40, 2017). PMID- 27393007 TI - Surgical outcomes of robotic thyroidectomy vs. conventional open thyroidectomy for papillary thyroid carcinoma. AB - BACKGROUND: The purpose of this study was to compare the surgical outcomes of robotic thyroidectomy (RT) using bilateral axillo-breast approach (BABA) with conventional open thyroidectomy (OT) in papillary thyroid carcinoma patients. METHODS: Between January 2009 and December 2013, 815 patients who had received thyroidectomy for papillary thyroid carcinoma were enrolled. Of these, 126 patients received RT and 689 patients underwent OT. Age, gender, body mass index, extent of surgery, tumor size, multiplicity, bilaterality, extrathyroidal extension, and tumor stage were used for the propensity score matching analysis. One hundred and nine patients were selected in each group, and surgical outcomes were compared between the two groups. RESULTS: The RT group showed a significantly longer operating time (290.6 +/- 74.4 vs. 107.9 +/- 30.8 min, P < 0.001). However, the mean hospital stay after surgery (3.6 +/- 0.8 vs. 3.4 +/- 1.2 days, P = 0.293), postoperative complication rates (major and minor, P = 0.754 and P = 0.852), and pain score (postoperative day, P = 0.669; postoperative day 1, P = 0.952) were comparable between the two groups. There was no difference in the number of metastatic lymph nodes, but the mean number of retrieved lymph nodes in the RT group was lesser than that in the OT group (3.5 +/- 3.5 vs. 5.3 +/- 5.2, P = 0.002). CONCLUSIONS: Robotic thyroidectomy via the BABA may be a safe and acceptable surgical technique. But, further development that resolves the limitation of central node dissection is needed. PMID- 27393009 TI - Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial. AB - BACKGROUND: A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period. METHODS: 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 MUg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann Whitney - Wilcoxon tests assessed differences between groups. RESULTS: Fifty seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (-0.04, 0.08) vs. placebo 0.22, 95 % CI (-0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (-0.14, 95 % CI (-0.48, 0.19) vs. placebo 0.44, 95 % CI (-0.15, 1.04), p = 0.042) although no significant effects were seen from the baseline visit, or in Hoffa-synovitis, effusion-synovitis, menisci and osteophytes. CONCLUSIONS: In this post-hoc analysis cartilage showed less worsening from baseline to 12 months in the PFJ, and BMLs showed more improvement from 6 to 12 months for the whole knee. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01033994 . PMID- 27393010 TI - Multiparametric characterization of neuronal subpopulations in the ventrolateral preoptic nucleus. AB - The characterization of neuronal properties is a necessary first step toward understanding how the ventrolateral preoptic nucleus (VLPO) neuronal network regulates slow-wave sleep (SWS). Indeed, the electrophysiological heterogeneity of VLPO neurons suggests the existence of subtypes that could differently contribute in SWS induction and maintenance. The aim of the present study was to define cell classes in the VLPO using an unsupervised clustering classification method. Electrophysiological features extracted from 289 neurons recorded in whole-cell patch-clamp allowed the identification of three main classes of VLPO neurons subdivided into five distinct subpopulations (cluster 1, 2a, 2b, 3a and 3b). The high occurrence of a low-threshold calcium spike (LTS) was one of the most distinctive features of cluster 1 and 3. Since sleep-promoting neurons are generally identified by their ability to generate an LTS and by their inhibitory response to noradrenaline (NA), 189 neurons from our dataset were also tested for this neurotransmitter. Neurons from cluster 3 were the most frequently inhibited by NA. Biocytin labeling and Neurolucida reconstructions of 112 neurons furthermore revealed a small dendritic arbor of cluster 3b neurons compared, in particular, to cluster 2b neurons. Altogether, we performed an exhaustive characterization of VLPO neuronal subtypes that is a crucial step toward a better understanding of the neuronal network within the VLPO and thereby sleep physiology. PMID- 27393011 TI - Serotype influences on dengue severity: a cross-sectional study on 485 confirmed dengue cases in Vitoria, Brazil. AB - BACKGROUND: Dengue is caused by a RNA virus of the family Flaviviridae, which presents four serotypes (DENV-1 to DENV-4) capable of inducing hemorrhage. The purpose of this study was to evaluate the influence of serotype on the outcome of dengue. METHODS: This cross-sectional study included data from dengue cases with serotyping results that occurred between 2009 and 2013 in Vitoria, Espirito Santo, Brazil. Data were accessed through the Information System for Notifiable Diseases. Chi-square test, Fisher exact test, Mann-Whitney U test, and logistic regression were performed to assess associations between different serotypes and dengue severity, while considering gender and age. RESULTS: The sample consisted of 485 laboratory confirmed dengue cases, of which 46.4 % were females, with median age of 26 years. Regarding overall samples, 77.3 % were caused by DENV-1, 16.1 % by DENV-4, 6.4 % by DENV-2, and 0.2 % by DENV-3. Severe dengue affected 6.6 % of all cases, of which 32.3 % of the cases caused by DENV-2, 6.4 % of those caused by DENV-4, 4.5 % of those caused by DENV-1, and none of those caused by DENV-3. Severe dengue was found to be seven times more frequent among cases of DENV-2 than among those of the other serotypes. CONCLUSIONS: The present study found that cases of DENV-2 had a higher proportion of severe dengue than among those of DENV-1 and DENV-4. Consequently, early detection of serotypes circulating in the territory could be an important approach to prevent increasing numbers of severe outcomes during dengue outbreaks by predicting the health support needed for early diagnoses and treatment of dengue cases. PMID- 27393012 TI - Increasing survival after admission to UK critical care units following cardiopulmonary resuscitation. AB - BACKGROUND: In recent years there have been many developments in post resuscitation care. We have investigated trends in patient characteristics and outcome following admission to UK critical care units following cardiopulmonary resuscitation (CPR) for the period 2004-2014. Our hypothesis is that there has been a reduction in risk-adjusted mortality during this period. METHODS: We undertook a prospectively defined, retrospective analysis of the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database (CMPD) for the period 1 January 2004 to 31 December 2014. Admissions, mechanically ventilated in the first 24 hours in the critical care unit and admitted following CPR, defined as the delivery of chest compressions in the 24 hours before admission, were identified. Case mix, withdrawal, outcome and activity were described annually for all admissions identified as post-cardiac arrest admissions, and separately for out-of-hospital cardiac arrest and in-hospital cardiac arrest. To assess whether in-hospital mortality had improved over time, hierarchical multivariate logistic regression models were constructed, with in hospital mortality as the dependent variable, year of admission as the main exposure variable and intensive care unit (ICU) as a random effect. All analyses were repeated using only the data from those ICUs contributing data throughout the study period. RESULTS: During the period 2004-2014 survivors of cardiac arrest accounted for an increasing proportion of mechanically ventilated admissions to ICUs in the ICNARC CMPD (9.0 % in 2004 increasing to 12.2 % in 2014). Risk-adjusted hospital mortality following admission to ICU after cardiac arrest has decreased significantly during this period (OR 0.96 per year). Over this time, the ICU length of stay and time to treatment withdrawal has increased significantly. Re-analysis including only those 116 ICUs contributing data throughout the study period confirmed all the results of the primary analysis. CONCLUSIONS: Risk-adjusted hospital mortality following admission to ICU after cardiac arrest has decreased significantly during the period 2004-2014. Over the same period the ICU length of stay and time to treatment withdrawal has increased significantly. PMID- 27393013 TI - Delayed bradykinin postconditioning modulates intrinsic neuroprotective enzyme expression in the rat CA1 region after cerebral ischemia: a proteomic study. AB - Pyramidal cells in the CA1 brain region exhibit an ischemic tolerance after delayed postconditioning; therefore, this approach seems to be a promising neuroprotective procedure in cerebral postischemic injury improvement. However, little is known about the effect of postconditioning on protein expression patterns in the brain, especially in the affected hippocampal neurons after global cerebral ischemia. This study is focused on the examination of the ischemia-vulnerable CA1 neuronal layer and on the acquisition of protection from delayed neuronal death after ischemia. Ischemic-reperfusion injury was induced in Wistar rats and bradykinin was applied 2 days after the ischemic insult in an attempt to overcome delayed cell death. Analysis of complex peptide CA1 samples was performed by automated two dimensional liquid chromatography (2D-LC) fractionation coupled to tandem matrix assisted laser desorption/ionization time of-flight (MALDI TOF/TOF) mass spectrometry instrumentation. We devoted our attention to differences in protein expression mapping in ischemic injured CA1 neurons in comparison with equally affected neurons, but with bradykinin application. Proteomic analysis identified several proteins occurring only after postconditioning and control, which could have a potentially neuroprotective influence on ischemic injured neurons. Among them, the prominent position occupies a regulator of glutamate level aspartate transaminase AATC, a scavenger of glutamate in brain neuroprotection after ischemia-reperfusion. We identified this enzyme in controls and after postconditioning, but AATC presence was not detected in the ischemic injured CA1 region. This finding was confirmed by two dimensional differential electrophoresis followed by MALDI-TOF/TOF MS identification. Results suggest that bradykinin as delayed postconditioning may be associated with modulation of protein expression after ischemic injury and thus this procedure can be involved in neuroprotective metabolic pathways. PMID- 27393015 TI - Safety and efficacy of cervical 10 kHz spinal cord stimulation in chronic refractory primary headaches: a retrospective case series. AB - BACKGROUND: Paresthesia-free cervical 10 kHz spinal cord stimulation (HF10 SCS) may constitute a novel treatment modality for headache disorders, when pharmacological approaches fail. We report the results of a retrospective analysis assessing the long-term safety, tolerability and efficacy of HF10 SCS in a group of patients with chronic refractory primary headache disorders. FINDINGS: Four patients with chronic migraine (CM), two with chronic SUNA (Short-lasting Unilateral Neuralgiform headache attacks with Autonomic symptoms) and one with chronic cluster headache (CCH) refractory to medical treatments, were implanted with cervical HF10 SCS. Pre- and post-implantation data were collected from the medical notes and from headache charts. At an average follow-up of 28 months (range: 12-42 months) we observed an improvement of at least 50 % in headache frequency and/or intensity in all CM patients. One SUNA patient became pain free and the other reported at least 50 % improvement in attacks frequency an duration. The CCH patient reported a significant reduction in CH attacks duration. Two patients underwent a surgical revision due to lead migration. CONCLUSIONS: Paresthesia-free high cervical HF10 SCS appears to be a long-term safe and likely effective therapeutic approach for patients with chronic refractory primary headache disorders. These results warrant further prospective studies in larger series of patients. PMID- 27393014 TI - Detection and Molecular Characterization of Gemycircularvirus from Environmental Samples in Brazil. AB - Gemycircularvirus (GemyCV) is a group of viruses which has been recently proposed as a new viral genus detected in fecal and environmental samples around the world. GemyCVs have been detected in human blood, brain tissue, cerebrospinal fluid, and stool sample. In the present study, we demonstrate for the first time, through molecular detection and characterization, the presence of GemyCVs in environmental samples from Brazil. Our results show a percentage of positivity ranging from 69 (25/36) to 97 % (35/36) in river water samples collected in Manaus, Amazon region, and wastewater from a wastewater treatment plant located in Rio de Janeiro, respectively, revealing GemyCVs as an important environmental contaminant. PMID- 27393017 TI - Coming in postgraduate medicine. PMID- 27393016 TI - Dynamic spatiotemporal brain analyses of the visual checkerboard task: Similarities and differences between passive and active viewing conditions. AB - We introduce a new analytic technique for the microsegmentation of high-density EEG to identify the discrete brain microstates evoked by the visual reversal checkerboard task. To test the sensitivity of the present analytic approach to differences in evoked brain microstates across experimental conditions, subjects were instructed to (a) passively view the reversals of the checkerboard (passive viewing condition), or (b) actively search for a target stimulus that may appear at the fixation point, and they were offered a monetary reward if they correctly detected the stimulus (active viewing condition). Results revealed that, within the first 168 ms of a checkerboard presentation, the same four brain microstates were evoked in the passive and active viewing conditions, whereas the brain microstates evoked after 168 ms differed between these two conditions, with more brain microstates elicited in the active than in the passive viewing condition. Additionally, distinctions were found in the active condition between a change in a scalp configuration that reflects a change in microstate and a change in scalp configuration that reflects a change in the level of activation of the same microstate. Finally, the bootstrapping procedure identified that two microstates lacked robustness even though statistical significance thresholds were met, suggesting these microstates should be replicated prior to placing weight on their generalizability across individuals. These results illustrate the utility of the analytic approach and provide new information about the spatiotemporal dynamics of the brain states underlying passive and active viewing in the visual checkerboard task. PMID- 27393019 TI - Problems Solutions. PMID- 27393018 TI - From the Editor-in-Chief. PMID- 27393020 TI - What's Happening in Medicine! PMID- 27393021 TI - Washington Report an Health. PMID- 27393022 TI - Allergic Rhinitis and Sinusitis. AB - Allergic rhinitis may often be satisfactorily managed by antihistamines, decongestants, and topical corticosteroids. When these simple methods fail, specific diagnosis and injection treatment (immunotherapy) by the specialist in allergy and immunology are in order. PMID- 27393023 TI - Immunologic Aspects of the Hematologic Neoplasms. AB - Understanding the pathogenesis and pathophysiology of the hematologic malignancies now requires knowledge of their immunology. Many of these tumors appear to arise from the immune cells themselves (B or T cell tumors); most have associated disturbances in immune cell function. New immunodiagnostic methods may become potentially useful clinical tools for evaluating extent of disease, tumor cell kinetics, response to treatment, and prognosis. PMID- 27393024 TI - The Hysterical personality. AB - When the hysterical person's immature, dependent needs are not met, she is prone to present physical complaints that simulate organic illness. Unless the physician recognizes the hysterical personality, all his therapeutic efforts with such a patient ultimately fail. PMID- 27393025 TI - Tracheal Fibroxanthoma in a Child. PMID- 27393027 TI - Meetings & courses. PMID- 27393026 TI - The Law/Medicine Letter: Educating for Leadership. AB - Under a new program, physicians studying for specialty certification will combine traditional medical courses with intensive education in economics, sociology, law, education, management, statistics, and related fields. Similar programs are designed to provide leadership training for law students who wish to acquire medicolegal skills. PMID- 27393028 TI - Multiple Disorders in African Bushman. PMID- 27393031 TI - Contrast CT-scan for preoperative planning of VSLN (vascularized submental lymph node) transfer. AB - BACKGROUND AND OBJECTIVES: Vascularized submental lymph-node (VSLN) transfer is gaining popularity as a reliable donor-site in microsurgical treatment of lymphedema. However, variations in number, location, and blood supply to submental lymph-nodes as well as associate skin-paddle make a predictable flap harvest a challenging task. We analyzed this region on preoperative imaging, to improve accuracy of VSLN transfers. METHODS: Contrast CT-scan analysis of VSLN flap areas was performed in 58 patients. Number and location of visibly vascularized lymph nodes as well as submental artery perforators were identified, documented, and compared. RESULTS: About 409 lymph-nodes were found in 50 patients. No significant difference was found in the number of nodes between the right and left side. Significantly more lymph-nodes were found in zones 1B than zones 1A. In eight patients nodes were not identified. In the remaining 50 patients position of the visibly vascularized submental lymph-node was predictable. CONCLUSION: Significantly less lymph-nodes can be found in zone 1a then zone 1b. Location of visibly vascularized lymph nodes can be identified predictably in relation to bony landmarks. Blood supply to 1a nodes and particularly location of dominant skin perforator is unpredictable due to potential crossover. Contrast CT scan can help identify location and blood supply to submental lymph-nodes in most patients. J. Surg. Oncol. 2017;115:23-26. (c) 2016 Wiley Periodicals, Inc. PMID- 27393032 TI - Is FFR-CT a "game changer" in the diagnostic management of stable coronary artery disease? AB - The introduction of fractional flow reserve computed tomography (FFR-CT) that is performed from static coronary CT angiography datasets may open new horizons in the diagnostic management of patients with suspected coronary artery disease. FFR CT has a high sensitivity and moderate specificity in identifying ischemia in intermediate coronary stenoses. It has been demonstrated that this technology has the potential to significantly reduce the number of invasive coronary angiograms and the rate of normal coronary angiograms that are not followed by an intervention. Furthermore, initial data indicate that FFR-CT may predict the hemodynamic effect of stenting and even of bypass surgery. Thus, FFR-CT, with its capacity to serve as an effective gatekeeper before invasive angiography and the option to virtually predict the success of revascularization, constitutes a completely new concept in managing patients with stable angina pectoris. Before this exciting technology can enter clinical practice, however, some evident limitations need to be overcome and significantly more data concerning accuracy and influence on clinical and economic outcome parameters need to be generated. PMID- 27393033 TI - Histopathological comparative analysis of periimplant bone inflammatory response after dental implant insertion using flap and flapless surgical technique. An experimental study in pigs. AB - AIM: To evaluate by histopathological analysis the peri-implant bone inflammation degree, in certain time intervals (7, 14, 21 and 28 days), following mini incision flapless and flap implant placement. MATERIAL AND METHODS: The experiment was conducted on four domestic pigs. Nine weeks prior to implant insertion, second and third mandibular premolars were extracted. Each animal received six implants in lower jaw. On one randomly chosen side of jaw flapless technique using mini-incision was performed, while on the other side implants were inserted after flap raising. After 7, 14, 21, and 28 days, the experimental animals were sacrificed. Following mandibular resection and decalcification, the samples for histopathological analysis of the peri-implant bone were obtained in the empty implant bed area, from the buccal side of the mandible, adjacent to implant neck region and parallel to crestal edge of implant bed. The degree of inflammatory response of the peri-implant bone was estimated through ordinal scores from 0 to 2. RESULTS: Seven days after the surgery all samples in the flap group had score 2 indicating high inflammation degree, in contrast to lower inflammatory reaction in flapless group. On the 14th and 21st postoperative day decreasing of inflammation degree was noted in all samples of the flapless group (score 1), while in flap group samples presented scores 1 and 2. Twenty-eight days after the implant placement, further reduction of inflammation in the flapless group (33% of samples had score 0) was observed. CONCLUSION: Flapless technique in comparison to conventional flap procedure minimizes postoperative bone inflammatory reactions. PMID- 27393034 TI - Carbon monoxide releasing molecule-2 ameliorates IL-1beta-induced IL-8 in human gastric cancer cells. AB - Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1beta-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1beta-induced IL 8 mRNA and protein expression as well as IL-8 promoter activity. IL-1beta induced the translocation of p47(phox) to activate reactive oxygen species (ROS) producing NADPH oxidase (NOX). Moreover, IL-1beta activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-kB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1beta-induced IL 8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-kB and AP-1 are critical for IL-1beta-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-kappaB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1beta-induced activation of ROS/NF-kB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment. PMID- 27393035 TI - Tetrachlorobenzoquinone induces Nrf2 activation via rapid Bach1 nuclear export/ubiquitination and JNK-P62 signaling. AB - Our previous studies demonstrated that tetrachlorobenzoquinone (TCBQ), an active metabolite of pentachlorophenol, has effects on the generation of reactive oxygen species (ROS) and oxidative stress in vitro and in vivo. Nuclear factor erythroid derived 2-like 2 (Nrf2) is a cellular sensor of electrophilic or oxidative stress that regulates the expression of antioxidant enzymes and defensive proteins. We have illustrated that TCBQ activates Nrf2 signaling by promoting the formation of the Kelch-like ECH-associated protein 1 (Keap1) cross-linking dimer and the formation of an ubiquitination switch from Nrf2 to Keap1. The activation of Nrf2 by TCBQ may serve as an adaptive response to a TCBQ-induced oxidative insult. BTB and CNC homolog 1 (Bach1) compete with Nrf2, leading to the negative regulation of the antioxidant response element (ARE). In this report, we propose that TCBQ induces the dynamic inactivation of Bach1. We observed a rapid nuclear efflux of Bach1 and an accumulation of Nrf2 in nuclei upon TCBQ treatment that precedes the binding of Nrf2 with ARE. We found that the nuclear export of Bach1 is dependent on its chromosomal region maintenance 1 (Crm1) interaction and tyrosine phosphorylation. Although TCBQ induces the ubiquitination of Bach1, TCBQ also increases the mRNA and protein levels of Bach1, returning Bach1 to normal levels. Moreover, we found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling. PMID- 27393036 TI - "Psychosexual Development Disorders": Calling and Recalling for Declassification. PMID- 27393037 TI - Perceived Effects of Pornography on the Couple Relationship: Initial Findings of Open-Ended, Participant-Informed, "Bottom-Up" Research. AB - The current study adopted a participant-informed, "bottom-up," qualitative approach to identifying perceived effects of pornography on the couple relationship. A large sample (N = 430) of men and women in heterosexual relationships in which pornography was used by at least one partner was recruited through online (e.g., Facebook, Twitter, etc.) and offline (e.g., newspapers, radio, etc.) sources. Participants responded to open-ended questions regarding perceived consequences of pornography use for each couple member and for their relationship in the context of an online survey. In the current sample of respondents, "no negative effects" was the most commonly reported impact of pornography use. Among remaining responses, positive perceived effects of pornography use on couple members and their relationship (e.g., improved sexual communication, more sexual experimentation, enhanced sexual comfort) were reported frequently; negative perceived effects of pornography (e.g., unrealistic expectations, decreased sexual interest in partner, increased insecurity) were also reported, albeit with considerably less frequency. The results of this work suggest new research directions that require more systematic attention. PMID- 27393038 TI - Observed Normativity and Deviance in Friendship Dyads' Conversations About Sex and the Relations With Youths' Perceived Sexual Peer Norms. AB - The current study examined the relations between observed normativity and deviance during adolescents' and young adults' conversations about sex with their friends and their individual perceptions of sexual peer norms. Participants were 16-21-year-old same-sex friendship dyads (31 male and 30 female dyads) who performed a peer interaction task that consisted of five discussion assignments focusing on party planning, sexual double standards, condom use, homosexuality, and consensual sex. Videotaped discussions were coded to capture the amounts of normative talk (e.g., consistent with notions of healthy sexuality) and deviant talk (e.g., consistent with notions of risky sexuality), and the verbal or nonverbal reinforcement thereof. Participants also completed individual questionnaires to assess their perceived sexual descriptive norms, injunctive norms, pressure, and risk norms among their peers. Actor-partner interdependence model (APIM) results revealed that youths' perceived descriptive, injunctive, and risk norms, but not their experienced peer pressure, were related to both their own (actor effects) and their friends' (partner effects) normativity and deviance. Overall, more deviance was related to perceiving friends to be more sexually active, more approving of having sex, and engaging in more risky sex, whereas more normativity was related to these perceptions in the opposite direction. Gender differences in the APIMs indicated that interactive normativity and deviance was related to perceived descriptive, injunctive, and risk norms for boys, but only to perceived injunctive norms for girls. These findings demonstrate the importance of assessing the dyadic nature of youths' sexual communication with friends, their relation to individual sexual peer norm perceptions, and gender differences therein. PMID- 27393039 TI - Perspectives on Sexual Identity Formation, Identity Practices, and Identity Transitions Among Men Who Have Sex With Men in India. AB - Men who have sex with men (MSM) remain at high risk for HIV infection. Culturally specific sexual identities, encompassing sexual roles, behavior, and appearance, may shape MSM's experiences of stigmatization and discrimination, and affect their vulnerability to HIV. This multi-site qualitative study (n = 363) encompassing 31 focus group discussions (FGDs) and 121 in-depth interviews (IDIs) across 15 sites in India investigated sexual identity formation, identity practices, and transitions and their implications for HIV prevention. IDIs and FGDs were transcribed, translated, and underwent thematic analysis. Our findings document heterogeneous sexual identity formation, with MSM who have more gender nonconforming behaviors or appearance reporting greater family- and community level disapproval, harassment, violence, and exclusion. Concealing feminine aspects of sexual identities was important in daily life, especially for married MSM. Some participants negotiated their identity practices in accordance with socioeconomic and cultural pressures, including taking on identity characteristics to suit consumer demand in sex work and on extended periods of joining communities of hijras (sometimes called TG or transgender women). Participants also reported that some MSM transition toward more feminine and hijra or transgender women identities, motivated by intersecting desires for feminine gender expression and by social exclusion and economic marginalization. Future studies should collect information on gender nonconformity stigma, and any changes in sexual identity practices or plans for transitions to other identities over time, in relation to HIV risk behaviors and outcomes. PMID- 27393040 TI - Basal Ganglia dysfunctions in movement disorders: What can be learned from computational simulations. AB - The basal ganglia are a complex neuronal system that is impaired in several movement disorders, including Parkinson's disease, Huntington's disease, and dystonia. Empirical studies have provided valuable insights into the brain dysfunctions underlying these disorders. The systems-level perspective, however, of how patients' motor, cognitive, and emotional impairments originate from known brain dysfunctions has been a challenge to empirical investigations. These causal relations have been analyzed via computational modeling, a method that describes the simulation of interacting brain processes in a computer system. In this article, we review computational insights into the brain dysfunctions underlying Parkinson's disease, Huntington's disease, and dystonia, with particular foci on dysfunctions of the dopamine system, basal ganglia pathways, and neuronal oscillations. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27393041 TI - Authors' response to the letter by Dr. Eisa-Beygi. PMID- 27393042 TI - The role of the store-operated calcium entry channel Orai1 in cultured rat hippocampal synapse formation and plasticity. AB - KEY POINTS: The role of non-synaptic calcium entry in the formation and functions of dendritic spines was studied in dissociated cultured rat hippocampal neurons. Orai1, a store-operated calcium channel, is found in dendritic spines. Orai1 co localizes in dendritic spines with STIM2 under conditions of lower [Ca2+ ]o. Orai1 channels are associated with the formation of new dendritic spines in response to elevated [Ca2+ ]o. Lack of Orai1, either by transfection with a dominant negative construct or with small interfering RNA to Orai1, results in retarded dendritic spines, an increase in density of filopodia, lower synaptic connectivity and the ability to undergo plastic changes. These results highlight a novel role for Orai1 in synapse formation, maturation and plasticity. ABSTRACT: The possible role of store operated calcium entry (SOCE) through the Orai1 channel in the formation and functions of dendritic spines was studied in cultured hippocampal neurons. In calcium store-depleted neurons, a transient elevation of extracellular calcium concentration ([Ca2+ ]o ) caused a rise in [Ca2+ ]i that was mediated by activation of the SOCE. The store depletion resulted in an increase in stromal interacting molecule 2 (an endoplasmic calcium sensor) association with Orai1 in dendritic spines. The response to the rise in [Ca2+ ]o was larger in spines endowed with a cluster of Orai1 molecules than in spines devoid of Orai1. Transfection of neurons with a dominant negative Orai1 resulted in retarded maturation of dendritic spines, a reduction in synaptic connectivity with afferent neurons and a reduction in the ability to undergo morphological changes following induction of chemical long-term potentiation. Similarly, small interfering RNA (siRNA)-treated neurons had fewer mature dendritic spines, and lower rates of mEPSCs compared to scrambled control siRNA treated neurons. Thus, influx of calcium through Orai1 channels facilitates the maturation of dendritic spines and the formation of functional synapses in central neurons. PMID- 27393043 TI - Erratum to: Anxious Imagery in Children With and Without Autism Spectrum Disorder: An Investigation into Occurrence, Content, Features and Implications for Therapy. PMID- 27393044 TI - Erratum to "The implications of endemic IMP-4 carbapenemase for clinical laboratory susceptibility testing" [J. Microbiol. Methods 124 (2016) 10-12]. PMID- 27393045 TI - To be spurned no more: The affective and behavioral consequences of social and nonsocial rejection. AB - Social pain is often associated with social rejection and shares neural correlates with the bothersome aspect of physical pain, which may also indicate an overlap in function. Pain has been described as a motivational signal to respond to the source of the pain in an adaptive way, such as by altering behavior. We tested whether social pain causes similarly adaptive alterations in behavior. Participants played computerized ball-tossing tasks with putative players-one who passed to and one who excluded the participant from play-in both a social and nonsocial version. We assessed the behavioral consequences of social pain by comparing the number of throws to each stimulus (social rejector vs. nonsocial rejector) over the course of the task. Posttask questionnaires assessed subjective feelings of social pain. A decrease in throws to the rejecting stimulus was only observed in the social version, indicating that rejection that is social in nature leads to change in behavior. Moreover, participants reported more negative feelings toward the rejecting stimulus in the social than in the nonsocial version. These subjective feelings of social pain mediated the effect of version of the game (social vs. nonsocial) on changes in behavior, indicating that social pain from social rejection causes changes in behavior. PMID- 27393046 TI - [Not Available]. PMID- 27393047 TI - What you Need to Know about the New Regulations for Biomedical Research in France. AB - The EC 2001/20 directive relating to the clinical trials of medicinal products was transposed into French law in 2004 by means of a public health law. But this transposition actually came into effect on 27 August 2006 by the implementation of decree no. 2006-477 of 26 April 2006 which has been followed subsequently by numerous statutory orders. A reading of these regulatory texts shows that the new provisions go far beyond the framework of the directive as they have been notably extended by the French legislator to encompass all the health products within the competence of the French Agency for Sanitary Safety in Health Products (Afssaps) as well as to other studies that do not involve health products. In addition, all research undertaken is from now subject to the prior, and jointly favourable, reasoned opinion of a CPP (Ethic Committee) and authorisation by Afssaps. These new regulations for biomedical research in France substantially modify and reinforce the previous provisions defined by the Huriet law of 1988, for safety, vigilance and traceability. PMID- 27393048 TI - [Not Available]. PMID- 27393049 TI - Use of the Foreign Studies: Transposition of the Results, Prediction of the Therapeutic Effects in the French Population, Modelling of the Public Health Interest. AB - More and more frequently, the health authorities and the French assessment agencies are led to issue Marketing Authorizations (MAs), give opinions on the eligibility for reimbursement of drugs or to draft recommendations for clinical practice based on the results of foreign studies. The results of these studies are more or less difficult to transpose to French practice. These difficulties generate varying degrees of uncertainty concerning the effect to be expected of a drug. A more or less extensive loss of effect is sometimes even predictable. Some of the difficulties in transposition are discussed in this article and proposals for action are made in order to allow one, in the long term, to predict in the most precise manner possible the effects to be expected from a drug in the French population and be able to verify this prediction at an interval from its eligibility for reimbursement. PMID- 27393050 TI - [Not Available]. AB - OBJECTIVE: Evaluate triptan prescriptions in ambulatory medicine. METHODS: Collection of medical data from 301 patients treated with triptans reimbursed by the French National Health Fund in the region of Midi-Pyrenees. RESULTS: Ninety five per cent of selected patients suffered from migraine condition according to the International Headache Society diagnosis criteria [Confidence interval (CI) 95%: 93-98]. Co-morbidity factors contra-indicating triptan therapy were present in 6% of patients (CI 95%: 3-9). 2% of patients were prescribed other medicinal products contra-indicated with their triptan therapy (CI 95%: 0-4). Twenty-six per cent of patients were taking triptan medicines more than 8 times per month over a period of three months (CI 95%: 21-31) and 8% were taking this treatment more than 12 times per month (CI 95%: 5-11). Eleven per cent kept written information of their migraine crises (CI 95%: 7-15). Thirty-nine per cent benefited from dedicated prophylactic treatments (CI 95%: 33-45). CONCLUSION: In a context of sustained increase in prescriptions of migraine treatments, it appears necessary to remain cautious about clinical and pharmacological contra indications. Prevention of abuse of medicines is based on a better use of crises agendas and introduction of prophylactic therapies. PMID- 27393051 TI - [Not Available]. PMID- 27393052 TI - Postgraduate Course of the Hepato-Biliary and Pancreatic Section (HBPS) of the Royal Belgian Society for Surgery (September 2001). PMID- 27393053 TI - Introduction. PMID- 27393056 TI - Synthesis and Root Growth-promoting Activity of Capillarol and Its Derivatives. AB - The root growth-promoting factor, capillarol, and derivatives were synthesized from p-hydroxybenzaldehyde by photo-Fries rearrangement and their root growth promoting activity for rice seedlings was studied. PMID- 27393057 TI - Water Sorption and Drying Behavior of Crosslinked Dextrans. AB - The water sorption and drying behavior of crosslinked dextran gels was investigated in relation to the dependency on the density of the crosslinks. Sorption isotherms indicate that the amount of sorption was more for the gels with a lower crosslink density. Almost all the isotherms show sorption and desorption hysteresis, the extent of this hysteresis being more marked with the gels with lower crosslink density. The rate of drying was also dependent on the crosslink density. These results can be explained by considering that the polymer network in a gel with a low crosslink density is more flexible to easy change during water sorption and drying than in one with a higher crosslink density. PMID- 27393054 TI - Mass Continuous Suture versus Layered Interrupted Suture in Transverse Abdominal Incision Closure after Liver Resection. AB - BACKGROUND: Abdominal incision closure technique seriously influences patient prognosis. Most studies have focused on the different suture techniques and materials on midline incision, while little data are available in wide transverse or oblique incisions after liver resection (LR). The aim of the present study is to compare the two major incision suture methods after LR in our institute: Mass continuous suture (group P) and layered interrupted suture (group S). STUDY DESIGN: 258 patients undergoing LR with abdominal transverse or oblique incisions were prospectively enrolled. They were divided into two groups according to different abdominal incision suture methods and compared with the preoperative, intraoperative parameters, and postoperative wound complications. RESULTS: There were 118 patients in group P and 140 patients in group S, which was similar in general condition, primary disease, liver, and renal function. Incision length, total operation time, intraoperative blood loss, or perioperative antibiotics use were not different between the two groups. However, abdominal incision closure time and interval time for stitches removing after operation was significantly shorter in group P than group S (both p < 0.001). After a median follow-up of 16 months, the incidence of wound infection and fat liquefaction was more than two times higher in group S than group P, which, however, was not statistically different. Moreover, there was no difference in wound disruption or incisional hernia between the two groups. CONCLUSIONS: Although similar in occurrence of postoperative wound complications, mass continuous suture with polydioxanone seemed to be more timesaving in incision closure and motivated in wound healing. PMID- 27393058 TI - Structure-Activity Relationship of Phloroglucinol Compounds from Eucalyptus as Marine Antifoulants. AB - Environmental pollution has resulted in the use of organo-tin and organo-copper compounds as antifouling agents being prohibited. Non-toxic natural products are considered to be environmentally friendly antifouling agents. Several phloroglucinol compounds isolated from three species of Eucalyptus have demonstrated strong attachment-inhibiting activity against the blue mussel. In this paper, we discuss the structure-activity relationship of these phloroglucinol compounds on the basis of molecular mechanics calculations. When these compounds were superimposed on each other and the strongest inhibitor was applied as a template, the repulsion energy of the other compounds was proportional to the logarithmic attachment-inhibiting activity. It is concluded that, of the two phloroglucinol rings in sideroxylonal A, ring C is more important, and those compounds that stereochemically and electrostatically resemble the template molecule are more active. PMID- 27393059 TI - Isolation and Properties of an Extracellular beta-Glucosidase from a Filamentous Fungus, Cladosporium resinae, Isolated from Kerosene. AB - An extracellular beta-glucosidase was purified from a culture filtrate of the fungus Cladosporium resinae strain NK-1 grown on a medium containing starch, Tween 80, and yeast extract. The purified enzyme was monomeric with an Mr 98,000, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and native gel filtration using HPLC. The enzyme had optimal activity with p nitrophenyl-beta-D-glucoside (PNPG) at 50 degrees C and pH 4.5. The enzyme catalyzed the hydrolysis of cellobiose and PNPG. The Km and Vmax with PNPG as the substrate at 50 degrees C and pH 4.5 were 0.07 mM and 364 MUmol/min/mg, respectively; with cellobiose as the substrate, the corresponding values were 2.3 mM and 75 MUmol/min/mg. The enzyme activity was competitively inhibited by glucose (Ki=20 mM), while fructose, galactose, mannose, arabinose, xylose (each at 50 mM), sucrose, and lactose (each at 30 mM) were not inhibitory. While the enzyme has activity against sophorose (beta-1,2-glucobiose) and laminaribiose (beta-1,3-glucobiose), it has no activity against gentiobiose (beta-1,6 glucobiose). The activity of the beta-glucosidase was inhibited by Ag(+), Fe(2+), Mn(2+), Zn(2+), Hg(2+), SDS, and p-chloromercuribenzoate. PMID- 27393060 TI - Enantioselective Relieving Activity of alpha-Methylbenzylphenylureas toward Bensulfuron-methyl Injury to Rice (Oryza sativa). AB - Optically active alpha-methylbenzylphenylureas were tested for their relieving activities toward just-germinated rice seedlings injured by bensulfuron-methyl (methyl 2- [[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]- sulfonyl]methyl]benzoate) in an agar test to evaluate the chiral requirement and enantioselectivity. Many kinds of derivatives of the alpha methylbenzylphenylureas exhibited strong relieving activity without any affect on root growth at the highest concentration tested. Six compounds with an (S) configuration were more active than daimuron. The log k' values of the most potent derivatives ranged from 0.42 to 0.65. A relatively strong parabolic relationship between the log k' value and the activity has only been found in the case of the (S)-enantiomers containing halogen atoms. The enantioselectivity of the chiral pairs was very high, and the chirality-activity function followed a Pfeiffer relationship, increasing the selectivity with increasing potency. Among them, the 2,3-Cl2, 2-F-4-CH3, 4-COOEt, 2-Cl and 2,5-F2 derivatives were highly enantioselective with a significantly high relieving activity. These results suggest that while hydrophobicity performed an important role, chirality and the mode of substitution essentially contributed to the activity. PMID- 27393061 TI - Production of Eicosapentaenoic Acid-Enriched Triacylglycerol by Mucor hiemalis HA 30. AB - Microorganisms that accumulated the eicosapentaenoic acid (EPA)-enriched triacylglycerol (TG), were screened for using yeast-malt medium containing 1% free EPA. The best strain was identified as Mucor hiemalis HA-30. The optimum culture conditions for the accumulation of EPA-enriched TG were : 3% soluble starch, 0.5% polypeptone, 0.3% yeast extract, 0.5% free EPA, and pH 6.0 at 25 degrees C. After the cultivation, 1.77 mg/ml of the TG with EPA purity of 79% was obtained. The EPA content in TG increased in conjunction with the EPA content of the supplemented free fatty acids or ethyl esters. Free EPA were more efficiently incorporated than the ethyl esters. Trieicosapentaenoyl glycerol (EPA, EPA, EPA) accounted for 73% of total TGs. PMID- 27393062 TI - Easy Preparation of Methyl 7-epi-Jasmonate and Four Stereoisomers of Methyl Cucurbate, and Assessment of the Stereogenic Effect of Jasmonate on Phytohormonal Activities. AB - To test the stereogenic effect of jasmonate on phytohormonal activities, methyl 7 epi-jasmonate (1b) and four stereoisomers of methyl cucurbate were easily prepared in racemic form: epimerization at the C-7 position of a commercially available methyl jasmonate (2b) with a base and subsequent fractional distillation gave a 46:54 mixture of 1b and 2b, whose reduction gave a mixture of methyl cucurbates (3-6). This synthetic chemistry was supplemented by molecular modeling and an NMR study on 1b and 2b. An assessment of the inhibitory activities of the prepared jasmonates on growth of the second leaf sheath of rice and on seed germination of cress clarified that the cis-configuration of the C-3 and C-7 side chains of jasmonate was an important factor for the high activities. In inhibiting the seed germination of cress, methyl 6-epi-cucurbate (4) exhibited activity that was markedly higher than the other compounds tested, showing that the stereochemistry at C-6 as well as at C-3 and C-7 was strictly recognized by this bioassay. PMID- 27393063 TI - Isolation of Some Glucosides as Aroma Precursors from Ginger. AB - A glycosidically bound fraction was prepared by adsorbing a 80% methanol extract from fresh rhizomes of ginger onto a column of Amberlite XAD-2 resin and successively eluting with ethyl acetate or methanol. Enzymatic hydrolysis of this fraction with an acetone powder prepared from fresh ginger and commercial glycosidase liberated such alcohols as geraniol, 2-heptanol, alpha-terpineol, nerol, linalool, and citronellol, suggesting that fresh ginger included glycosides and glycosidase. The ethyl acetate eluate was chromatographed by an ODS flash column and then HPLC to isolate the beta-glucopyranosides of 5 hydroxyborneol, 1,8-epoxy-p-menthan-3-ol, (2E, 6E)- and (2E, 6Z)-3,7-dimethyl-8 hydroxyoctadien-1-ol, 2-heptanol, geraniol, nerol, (R)-linalool, and citronellol. All the glucosides, except for 5-hydroxybornyl-O-beta-D-glucopyranoside, were identified for the first time in the rhizome of ginger, and many of their aglycons were major constituents of the essential oil. The results indicate that these glucosides are aroma precursors of fresh ginger. PMID- 27393064 TI - Convenient Preparation and Quantification of 5,5'-Diferulic Acid. AB - 5,5'-Diferulic acid (5,5'-DFA), which is one of the cross-linking residues in plant cell walls, was prepared by using a facile procedure. The phenol oxidation of vanillin with FeCl3 gave divanillin, which was further devoted to a Perkin reaction to give the desired product. It was found on (13)C-NMR that the chemical shift of C-5 of ferulic acid (FA) clearly shifted downfield, when this carbon is quaternarized by the oxidative dimerizaton to 5,5'-DFA, while those of other carbons of 5,5'-DFA are fundamentally same as those of FA. Also prepared was [9,9'-(13)C2]-5,5'-DFA, which was proved to be a good internal standard on GC-MS quantification of endogenous 5,5'-DFA from plant tissues. PMID- 27393065 TI - Crystalline NADP-Dependent D-Mannitol Dehydrogenase from Gluconobacter suboxydans. AB - D-Mannitol dehydrogenase (EC 1.1.1.138) was purified and crystallized for the first time from the cell-free extract of Gluconobacter suboxydans IFO 12528. The enzyme was purified about 100-fold by a procedure involving ammonium sulfate fractionation, DEAE-Sephadex A-50 column chromatography, and gel filtration by a Sephadex G-75 column. The enzyme was completely separated from a similar enzyme, NAD-dependent D-mannitol dehydrogenase (EC 1.1.1.67), during enzyme purification. There being sufficient purity of the enzyme at this stage, the enzyme was crystallized, by the addition of ammonium sulfate, to fine needles. The crystalline enzyme showed a single sedimentation peak in analytical ultracentrifugation, giving an apparent sedimentation constant of 3.6 s. The molecular mass of the enzyme was estimated to be 50 kDa by SDS-PAGE and gel filtration chromatography. Oxidation of D-mannitol to D-fructose and reduction of D-fructose to D-mannitol were specifically catalyzed with NADP and NADPH, respectively. NAD and NADH were inert for the enzyme. Since the reaction equilibrium declined to D-fructose reduction over a wide pH range, the enzyme showed several advantages for direct enzymatic measurement of D-fructose. Even in the presence of a large excess of D-glucose and other substances, oxidation of NADPH to NADP was highly specific and stoichiometric to the D-fructose reduced. PMID- 27393066 TI - Preparation of Phage-insensitive Strains of Tetragenococcus halophila and Its Application for Soy Sauce Fermentation. AB - We attempted to breed phage-insensitive strains of Tetragenococcus halophila D10. Phage contact during selection initially caused the occurrence of lysogeny. Subsequently, we screened phage-insensitive mutants by replica plating so that mutant cells did not touch the phage during selection. Two strains were selected from about 150,000 strains. They grew normally in soy sauce mash (moromi) in the presence of phage phiD-10, although they had a similar extent of adsorption of phiD-10 as did the parent strain. PMID- 27393067 TI - Isolation of a 2-Pyrone Compound as an Antioxidant from a Fungus and Its New Reaction Product with 1,1-Diphenyl-2-picrylhydrazyl Radical. AB - The indophenol-reducing compound, 4-hydroxy-3,6-dimethyl-2H-pyrane-2-one (I), was isolated from the culture filtrate of an unidentified fungus. I also reacted with the DPPH radical to form a reaction product IV which was determined to be 1-[4 (3,4-dihydro-3,6-dimethyl-2,4-dioxo- 2H-pyran-3-yl)phenyl]-1-phenyl-2 picrylhydrazine. This is the first report describing the formation of an adduct of the DPPH radical and its scavenger. PMID- 27393068 TI - Antioxidative Activity of a Cathodic Solution Produced by the Electrolysis of a Dilute NaCl Solution. AB - The effectiveness was evaluated of a cathodic solution prepared by the electrolysis of an NaCl solution in inhibiting the aqueous oxidation of ethyl linoleate and ethyl docosahexaenoate. The decrease in unoxidized substrate and the formation of total peroxides during oxidation indicate that the cathodic solution completely inhibited the oxidation of both ethyl esters, while these lipids were easily oxidized in an NaCl solution and in distilled water. The antioxidative activity of the cathodic solution was confirmed after open incubation for 3 days and 7 days at 37 degrees C, although the scavenging ability of the cathodic solution toward DPPH radicals disappeared during this incubation. PMID- 27393069 TI - New Synthesis of Optically Active O-Aryl O-Ethyl Phenylphosphonothionates. AB - The mixed anhydride method was applied to synthesize O-aryl O-ethyl phenylphosphonothionate. The reaction of O, O-diethyl phosphorochloridate with O ethyl phenylphosphonothioic acid afforded O, O-diethyl phosphoric O-ethyl phenylphosphonothioic anhydride in a good yield. This anhydride was converted to O-aryl O-ethyl phenylphosphonothionates by reacting with the appropriate sodium phenoxide. This esterification occurred without racemization and produced optically pure O-ethyl O-(4-nitrophenyl) phenylphosphonothionate (EPN) and O-(4 cyanophenyl) O-ethyl phenylphosphonothionate (cyanofenphos). PMID- 27393070 TI - Substrate Specificity of Aqualysin I Altered by an Organic Solvent, DMSO. AB - Aqualysin I is the alkaline serine protease isolated from an extreme thermophile, Thermus aquaticus YT-1. We have analyzed the kinetic properties of aqualysin I, using thirty-one kinds of chromogenic succinyl-tripeptide p-nitroanilides as substrates in the presence of 10% dimethylsulfoxide (DMSO). Aqualysin I hydrolyzed many peptides in a DMSO-containing mixture, however the substrate specificity was different from that in the absence of DMSO. The Km for each peptide was raised by the addition of 10% DMSO. Also, the P3- as well as P2 specificity of aqualysin I was altered. These results suggested that the side chains of the P2 and P3 residues are exposed to the solvent, and the hydrophobic interactions between the side chain of the substrate and the solvent may take a part in the substrate recognition of the enzyme. PMID- 27393071 TI - An improved method for the cost-effective expression and purification of large quantities of KcsA. AB - KcsA, the bacterial K(+) channel from Streptomyces lividans, is the prototypical model system to study the functional and structural correlations of the pore domain of eukaryotic voltage-gated K(+) channels (Kv channels). It contains all the molecular elements responsible for ion conduction, activation, deactivation and inactivation gating [1]. KcsA's structural simplicity makes it highly amenable for structural studies. Therefore, it is methodological advantageous to produce large amounts of functional and properly folded KcsA in a cost-effective manner. In the present study, we show an optimized protocol for the over expression and purification of large amounts of high-quality, fully functional and crystallizable KcsA using inexpensive detergents, which significantly lowered the cost of the purification process. PMID- 27393072 TI - Methods for Evaluating Right Ventricular Function and Ventricular-Arterial Coupling. AB - Right ventricular function (RVF) carries great prognostic significance in heart failure and pulmonary hypertension (PH). Although there is considerable focus on RVF in pulmonary arterial hypertension, RVF is also of great importance in group 2 PH. This article will discuss assessment of RVF and evaluation of the Right Ventricle-Pulmonary Artery (RV-PA) coupling relationship. Cardiac imaging modalities allow direct visualization and assessment of RVF. Imaging modalities include the commonly utilized echo-Doppler imaging evaluating RV fractional area change, tricuspid annular plane systolic excursion and Tissue Doppler Imaging, in addition to the increasingly utilized cardiac magnetic resonance. Invasive hemodynamic assessment also plays an important role and can also be employed during exercise to help elucidate functional reserve. Cardiopulmonary exercise testing provides added insight into the mechanisms of cardiopulmonary disease. Cardiac imaging, invasive hemodynamics, and gas exchange stress testing can be combined to give a more sophisticated understanding of RVF. The RV-PA coupling relationship can be assessed using practical and clinically available metrics in order to gain clinically relevant understanding of the patients' physiologic state. RV-PA coupling assessments can be done using invasive, combined noninvasive-invasive, or non-invasive approaches. We also discuss our approaches in the assessment of the RV-PA coupling relationship. PMID- 27393073 TI - The genetics of extreme microgeographic adaptation: an integrated approach identifies a major gene underlying leaf trichome divergence in Yellowstone Mimulus guttatus. AB - Microgeographic adaptation provides a particularly interesting context for understanding the genetic basis of phenotypic divergence and may also present unique empirical challenges. In particular, plant adaptation to extreme soil mosaics may generate barriers to gene flow or shifts in mating system that confound simple genomic scans for adaptive loci. Here, we combine three approaches - quantitative trait locus (QTL) mapping of candidate intervals in controlled crosses, population resequencing (PoolSeq) and analyses of wild recombinant individuals - to investigate one trait associated with Mimulus guttatus (yellow monkeyflower) adaptation to geothermal soils in Yellowstone National Park. We mapped a major QTL causing dense leaf trichomes in thermally adapted plants to a <50-kb region of linkage Group 14 (Tr14) previously implicated in trichome divergence between independent M. guttatus populations. A PoolSeq scan of Tr14 region revealed a cluster of six genes, coincident with the inferred QTL peak, with high allele frequency differences sufficient to explain observed phenotypic differentiation. One of these, the R2R3 MYB transcription factor Migut.N02661, is a plausible functional candidate and was also strongly associated (r2 = 0.27) with trichome phenotype in analyses of wild-collected admixed individuals. Although functional analyses will be necessary to definitively link molecular variants in Tr14 with trichome divergence, our analyses are a major step in that direction. They point to a simple, and parallel, genetic basis for one axis of Mimulus guttatus adaptation to an extreme habitat, suggest a broadly conserved genetic basis for trichome variation across flowering plants and pave the way for further investigations of this challenging case of microgeographic incipient speciation. PMID- 27393074 TI - Serum MX2 Protein as Candidate Biomarker for Early Pregnancy Diagnosis in Buffalo. AB - Interferon-tau (IFN-tau)-induced molecular markers such as ubiquitin-like modifier (ISG15), 2',5'-oligoadenylate synthetase 1 (OAS1) and myxovirus resistance genes (MX1 and MX2) have generated immense attention towards developing diagnostic tools for early diagnosis of pregnancy in bovine. These molecules are expressed at transcriptional level in peripheral nucleated cells. However, their presence in the serum is still a question mark. This study reports sequential changes in expression of MX2 transcript in whole blood and serum MX2 protein level on days 0, 7, 14, 21, 28 and 35 in pregnant (n = 9) buffalo heifers, and on days 0, 7 and 14 in non-inseminated (n = 8) and inseminated non pregnant (n = 10) control animals. In non-inseminated and inseminated non pregnant heifers, the differential expression of MX2 transcript and MX2 protein level remained similar between day 7 and 14 post-oestrus. However, in pregnant heifers, on 14th and 28th day post-insemination MX2 transcript was 16.38 +/- 1.57 and 28.16 +/- 1.91 times upregulated as compared to day 0. Similarly, serum MX2 protein concentration followed analogous trend as MX2 transcript and increased gradually with the progression of pregnancy. Correlation analysis between expression of MX2 transcript and its serum protein level showed a significant positive correlation in pregnant animals, while it was random in other two groups. Therefore, MX2 surge at transcriptional and serum protein level after day 14-28 of pregnancy in buffalo holds potential for its use in early pregnancy detection. PMID- 27393075 TI - [Not Available]. AB - Since the full implementation in France of the European Directive 2001/20/EC about biomedical research, a written information form must be given to any participant in research, who must give in return his / her written consent. The written and consent form must be validated by a referent ethics committees prior to the research, but guidelines for the redaction of such document are missing. Thus, the investigators who are often in charge of the redaction could be helped by a tutorial that may consider the legal aspects, the rights of the participant and the quality of information. For this, a group from the French network of the clinical investigation centres - directed by the Inserm - worked on a tutorial which is presented here. This tutorial has been built stepwise, with review of the literature, enquiry within the French clinical investigation centres, primary redaction, internal validation, and final validation by external experts versed in the field of ethics for biomedical research. PMID- 27393076 TI - Religious Service Attendance and Lower Depression Among Women-a Prospective Cohort Study. AB - OBJECTIVE: Previous studies on the association between religious service attendance and depression have been mostly cross-sectional, subject to reverse causation, and did not account for the potential feedback between religious service attendance and depression. We prospectively evaluated evidence whether religious service attendance decreased risk of subsequent risk of depression and whether depression increased subsequent cessation of service attendance, while explicitly accounting for feedback with potential effects in both directions. METHOD: We included a total of 48,984 US nurses who were participants of the Nurses' Health Study with mean age 58 years and who were followed up from 1996 to 2008. Religious service attendance was self-reported in 1992, 1996, 2000, and 2004. Depression was defined as self-reported physician-diagnosed clinical depression, regular anti-depressant use, or severe depressive symptoms. Multivariate logistic regression and marginal structural models were used to estimate the odds ratio of developing incident depression, adjusted for baseline religious service attendance, baseline depression, and time-varying covariates. RESULTS: Compared with women who never attended services, women who had most frequent and recent religious service attendance had the lowest risk of developing depression (odds ratio [OR] = 0.71, 95 % confidence interval [CI] 0.62 0.82). Compared with women who were not depressed, women with depression were less likely to subsequently attend religious services once or more per week (OR = 0.74, 95 % CI 0.68-0.80). CONCLUSIONS: In this study of US women, there is evidence that higher frequency of religious service attendance decreased the risk of incident depression and women with depression were less likely to subsequently attend services. PMID- 27393077 TI - Cardiovascular emergencies and cardiac arrest in a pregnant woman. PMID- 27393078 TI - Seizures in the peripartum period: Epidemiology, diagnosis and management. AB - The occurrence of seizures in the peripartum period is a rare but particularly challenging situation. Seizures in the peripartum period could result from three categories of conditions: first and most frequent is the exacerbation of a known pre-existing seizure disorder, mainly epilepsy. A therapeutic evaluation is needed; second is the new onset of seizures due to a non-pregnancy-related problem. An accurate diagnosis and a specific treatment are required; third is range of pregnancy-related conditions. The present review focuses on this third category, with a special attention to disorders occurring in the peripartum period. It is structured in two sections. The first section is a focus on eclampsia since, based on ICU admission data, it appears to be the leading cause of pregnancy-related seizures. Its epidemiology, pathophysiology, clinical diagnosis, neuro-imaging features and recommended management are reviewed. The efficacy and safety of the recommended regimens of MgSO4 therapy are discussed, as well as controversies on the alteration of these regimens and the use of MgSO4 in women with mild preeclampsia. In the second section, the other causes of pregnancy-related new onset seizures are summarized. These include posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, thrombotic thrombocytopenic purpura, amniotic fluid embolism, and air embolism. Noteworthy is the fact that most of these pregnancy-related seizure conditions overlap with each other, mainly in terms of clinical presentations and neuro-imaging. Therefore, the diagnosis and the treatment options should be considered on a multidisciplinary basis. PMID- 27393079 TI - A descriptive, cross-sectional study characterizing bone erosions in rheumatoid arthritis and gout by ultrasound. AB - The aim of this study is to characterize bone erosions in metatarsal heads (MTH) in rheumatoid arthritis (RA) and gout by grayscale ultrasound. In a descriptive, cross-sectional study, we evaluated 40 patients with RA and 40 with gout, both diagnosed according to the American College of Rheumatology/European League Against Rheumatism criteria, respectively. All patients had bone erosion demonstrated by ultrasound, which was used, following OMERACT criteria, to describe the shape, size, number, border definition, overhanging margin, topography (intra- or extra-articular), and distribution (over dorsal, medial, lateral, or plantar aspect) of the lesions in the MTH. Descriptive statistics were used and a concordance exercise between two ultrasonographers blinded to the diagnosis was performed. Bone erosions in RA were observed most frequently at the plantar and lateral aspect of the fifth MTH, round in 96 %, small-sized (2.43 +/- 0.9 mm), intra-articular (100 %), and single (75 %). Few bone erosions had a well defined border an overhanging margin while in gout were found most frequently in the medial and dorsal aspect of the first MTH, single in 71 %, intra-articular in 100 %, and of median size (4.0 +/- 2.3). For shape, 51 % was round and 49 % was oval. A well-defined border was present in 39 %, and an overhanging margin in 62 %. Inter-rater reliability kappa was excellent (0.81, 95 % CI 0.56-1.00). Some characteristics of bone erosions in RA, including shape, size, ill-defined border, and localization in the fifth MTH could distinguish the lesions from gout. Grayscale US has excellent reliability to describe bone erosions in RA and gout. PMID- 27393080 TI - Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects. AB - OBJECTIVE: To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. STUDY DESIGN: A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m2) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. RESULTS: Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. CONCLUSIONS: Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. IMPLICATIONS: A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. PMID- 27393081 TI - Pre-stimulus beta and gamma oscillatory power predicts perceived audiovisual simultaneity. AB - Pre-stimulus oscillation activity in the brain continuously fluctuates, but it is correlated with subsequent behavioral and perceptual performance. Here, using fast Fourier transformation of pre-stimulus electroencephalograms, we explored how oscillatory power modulates the subsequent discrimination of perceived simultaneity from non-simultaneity in the audiovisual domain. We found that the over-scalp high beta (20-28Hz), parieto-occipital low beta (14-20Hz), and high gamma oscillations (55-80Hz) were significantly stronger before audition-then vision sequence when they were judged as simultaneous rather than non simultaneous. In contrast, a broad range of oscillations, mainly the beta and gamma bands over a great part of the scalp were significantly weaker before vision-then-audition sequences when they were judged as simultaneous versus non simultaneous. Moreover, for auditory-leading sequence, pre-stimulus beta and gamma oscillatory power successfully predicted subjects' reports of simultaneity on a trial-by-trial basis, with stronger activity resulting in more simultaneous judgments. These results indicate that ongoing fluctuations of beta and gamma oscillations can modulate subsequent perceived audiovisual simultaneity, but with an opposing pattern for auditory- and visual-leading sequences. PMID- 27393082 TI - Kinases inhibitors in lung cancer: From benchside to bedside. AB - Lung cancer still remains one of the major causes of cancer related mortality around the globe. Various different molecular targets have been discovered till date for targeting lung cancer. But not every new molecular target has a successfully designed inhibitor; moreover conventional chemotherapeutics have their own limitations such as toxicity and lack of selectivity. Thus, kinases still remain the most effective molecular target in lung cancer therapy. Also, once-shunned kinase inhibitors have recently acquired renewed interest after the development and approval of irreversible kinase inhibitors (such as afatinib) that form covalent bonds with cysteine (or other nucleophilic residues) in the ATP-binding pocket of the kinases. Irreversible kinase inhibitors have a number of potential advantages over conventional reversible kinase inhibitors including prolonged pharmacodynamics, suitability for rational design, high potency etc. This review reveals the current knowledge of all the chemical scaffolds, approved and/or investigational, utilized as inhibitors in lung cancer. It also explains the rationale of designing these along with possible interactions with their targets, biological data and possible problems associated with these inhibitors. PMID- 27393083 TI - Still Separate, Still Unequal: Social Determinants of Playground Safety and Proximity Disparities in St. Louis. AB - Physical activity among youth is shaped by the natural and built environment within which they live; however, few studies have focused on assessing playground safety and proximity in detail as part of the built environment for youth physical activity. We analyzed data on 100 publicly accessible playgrounds from Play Across St. Louis, a community-partnered study of the built environment for youth physical activity. Outcomes included overall playground safety, maintenance, and construction scores; distance to nearest playground; and distance to nearest top playground. Independent variables included neighborhood % youth, % black residents, % owner-occupied units, and % vacant units. Playgrounds in the city have varying degrees of safety and proximity. Mean overall playground safety score was 67.0 % (CI = 63.5, 70.4). Neighborhood % youth and % black residents were inversely associated with overall playground safety (p = 0.03 and p < 0.01) and maintenance (p < 0.01 and p < 0.0001). Mean distance to nearest playground was 638.1 and 1488.3 m to nearest top playground. Clusters of low safety scores were found in the northern and central areas while all high safety score clusters were found in the southern part of St. Louis. Public playground safety and proximity vary across St. Louis neighborhoods, especially by neighborhood demographics. Disparities in playground safety and proximity reveal an opportunity to develop community-wide interventions focused on playgrounds for youth activity. Further work is needed to examine the association between playground safety, proximity, and use and youth physical activity and weight. PMID- 27393084 TI - [Basis cream DAC in the context of traditional creams]. PMID- 27393085 TI - [Progressive facial hyperpigmentation]. PMID- 27393086 TI - [Primary cutaneous cryptococcosis : Pigeons can carry more than letters ...!] AB - In the event of non-specific epidermal lesions, the importance of a comprehensive anamnesis becomes especially apparent. In the following, we report on a patient case in which only a focused anamnesis was able to bring light into the darkness of numerous differential diagnoses - and to produce the diagnosis of a rare but in this collective common illness: primary cutaneous cryptococcosis. PMID- 27393087 TI - Zika virus infections: An overview of current scenario. AB - Zika virus (ZIKV) was discovered more than half a century ago, recently it has gained unprecedented attention by the global health community. Until 2007, only 14 cases of human ZIKV infections were reported around the globe, while during the current outbreak, estimated cases mounted to approximately 1.5 million in Brazil alone, the virus was disseminated to wider South-American territories and travel-associated ZIKV infections were reported in USA, Europe and recently in China. ZIKV infections remain asymptomatic in approximately 80% of the individuals, and no anti-viral treatments were recommended. Yet, neurological complications associated with the infections, such as infant microcephaly and Guillain-Barre syndrome are major cause of the concern. Although, based on small numbers of cases, existing evidence strongly supports an exclusive link of viral infection and observed neurological complications. However, much work remains to assign exact numbers of complications caused by ZIKV. Regarding its structural attributes ZIKV shows remarkable resemblance with dengue virus and West-Nile virus. Despite, genomes of different ZIKV strains have already been decoded; role of the viral components in infection process and particularly pathogenesis of the disease remain widely unclear. In vulnerable areas, most viable strategy to ensure public health safety is vector control and enhanced public awareness about the transmission of the disease. PMID- 27393088 TI - Zika virus, a pathway to new challenges. AB - The current Zika outbreak is largest of its kind with 1.4 million cases in Brazil alone. World Health Organization declared the current outbreak as the public health emergency of international concerns. The major route of Zika virus transmission is mosquito bites. Sexual transmission and monkey bites are also observed in few cases. There is dire need to evaluate the other routes of transmission like blood transfusion, lactation and contact with body fluids. Zika virus is infecting infants, not only causing microcephaly but also creating number of complications resulting in bad outcomes of pregnancy. In Brazil alone, 4000 cases of microcephaly have observed during the current outbreak. The incidence of Guillain-Barre (GB) syndrome is also observed during the current Zika virus outbreak. GB syndrome is acute medical condition leading the patients to death due to weakness of respiratory muscles or can cause the life time disability. There is no anti-viral drug or vaccine available for Zika virus. Zika infection can be prevented by using mosquito repellents, mosquito nets, cooling rooms by air conditions and wearing full sleeves or permethrin-treated clothes. The current outbreak of Zika has not only affected the health care but also caused great economic loss. Estimated loss in Latin America and Caribbean is US$3.5 billion. United Nation's sustainable development goal 3.d stresses the strengthening of early warning, risk reduction and management of national and global health risks. The world will keep on facing new challenges in the form of Ebola or Zika; there is strong need to prepare ourselves for any disease outbreak. PMID- 27393089 TI - Molecular epidemiology and phylogeny of Nipah virus infection: A mini review. AB - Nipah virus (NiV) is a member of the genus Henipavirus of the family Paramyxoviridae, characterized by high pathogenicity and endemic in South Asia. It is classified as a Biosafety Level-4 (BSL-4) agent. The case-fatality varies from 40% to 70% depending on the severity of the disease and on the availability of adequate healthcare facilities. At present no antiviral drugs are available for NiV disease and the treatment is just supportive. Phylogenetic and evolutionary analyses can be used to help in understanding the epidemiology and the temporal origin of this virus. This review provides an overview of evolutionary studies performed on Nipah viruses circulating in different countries. Thirty phylogenetic studies have been published from 2000 to 2015 years, searching on pub-med using the key words 'Nipah virus AND phylogeny' and twenty-eight molecular epidemiological studies from 2006 to 2015 have been performed, typing the key words 'Nipah virus AND molecular epidemiology'. Overall data from the published study demonstrated as phylogenetic and evolutionary analysis represent promising tools to evidence NiV epidemics, to study their origin and evolution and finally to act with effective preventive measure. PMID- 27393090 TI - Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice. AB - OBJECTIVES: To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract (GCBE) in high-fat diet (HFD)-induced obese mice. METHODS: Obesity was induced in mice using a HFD for four weeks. Then, mice were fed only HFD or HFD with GCBE at 50, 100, and 200 mg/kg. Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay. Body fat reduction was measured through dual-energy X-ray absorptiometry. RESULTS: In HFD-induced obese mice, GCBE treatment significantly decreased body weight gain, liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones, like adiponectin and leptin. GCBE treatment decreased mRNA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver, and decreased the corresponding protein expression. Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high fat and those treated with GCBE. GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased. CONCLUSIONS: GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver. PMID- 27393091 TI - Hepatoprotective properties of oleanolic and ursolic acids in antitubercular drug induced liver damage. AB - OBJECTIVE: To estimate to what extent the mixture of ursolic acid and oleanolic acid, in addition to the antitubercular standard regime, affects the hepatotoxicity profile. METHODS: Liver injury was induced in male BALB/c mice by administering, per os and daily for 11 weeks, a combination of anti-Tubercular (anti-TB) agents Rifampicin (10 mg/kg), Isoniazid (10 mg/kg), and Pyrazinamide (30 mg/kg). The ursolic acid and oleanolic acid mixture at doses of 100 or 200 MUg/mouse/day was subcutaneously injected throughout the entire study period (11 weeks). Biochemical and hematological analysis was supplemented by liver histological examination. RESULTS: Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs. CONCLUSIONS: The triterpene mixture was able to prevent the steatosis induced by the anti-TB drugs. PMID- 27393092 TI - Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents. AB - OBJECTIVE: To evaluate whether hypoxia inducible factor (HIF-1alpha) targeting pharmacological drugs, echinomycin, resveratrol and CdCl2 which inhibit HIF 1alpha stimulation, and mimosine, which enhances the stability of HIF-1alpha present antileishmanial properties. METHODS: The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous leishmaniosis. RESULTS: Resveratrol and CdCl2 reduced the parasite load [IC50, (27.3 +/- 2.25) MUM and (24.8 +/- 0.95) MUM, respectively]. The IC50 value of echinomycin was (22.7 +/- 7.36) nM and mimosine did not alter the parasite load in primary macrophages. The macrophage viability IC50 values for resveratrol, echinomycin and CdCl2 and mimosine were >40 MUM, >100 nM, >200 MUM and>2000 MUM, respectively. In vivo no differences between cutaneous lesions from control, resveratrol- and echinomycin-treated Balb/c mice were detected. CONCLUSIONS: Resveratrol, echinomycin and CdCl2 reduce parasite survival in vitro. The HIF 1alpha targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies. PMID- 27393093 TI - High seroprevalence of asymptomatic viral haemoparasites among prospective blood donors in Nigeria. AB - OBJECTIVE: To determine the prevalence of viral haemoparasites in prospective Nigerian blood donors. METHODS: Ethical clearance was obtained and informed consent questionnaires were distributed to blood donors to obtain their demographical data. A total of 186 blood donors from LAUTECH Teaching Hospital, Osogbo were tested for hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) using rapid test kit and enzyme linked immunosorbent assay. RESULTS: The highest prevalence of blood transmitted infections was 182 (97.85%) while the prevalence of HIV, HAV, HBV and HCV were 6.45%, 97.85%, 14.52% and 3.23%, respectively. Highest seroprevalence for hepatitis A, B and C occurred among low risk occupation. There was no significant association between all the hepatitis viruses and demographic factors except occupation with P value of 0.002 7. Hepatitis A, B and C seropositive blood donors on average tend to have PCV within the normal reference range. Out of the 27 hepatitis B positive blood donors, 22 were donating blood for the first time while 5 were repeat donors. None of the hepatitis C seropositive donors have been exposed to blood or any form of its products and were all donating blood for the first time. However, the distribution of donor type for HAV is random. CONCLUSIONS: The prevalence of HAV, HBV, HCV and HIV among prospective donors in Nigeria is alarming particularly HAV. These infections can be transmitted to recipients if proper screening is not carried out, hence they should be included as a routine test for blood donors. PMID- 27393094 TI - Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity. AB - OBJECTIVE: To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). METHODS: Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test. RESULTS: Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test. Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex. Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine. Scallop shell extract also suppressed the increase in locomotor activity induced by MK801. CONCLUSIONS: Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801 induced hyperlocomotion. PMID- 27393095 TI - Study on the therapeutic mechanisms of pseudolaric acid in mice with allergic contact dermatitis. AB - OBJECTIVE: To study the therapeutic mechanisms of pseudolaric acid on allergic contact dermatitis in mice. METHODS: A total of 50 BALB/C mice were selected and randomly divided into control group, model group, and treatment A, B, C groups with 10 rats in each group. ACD model was established in model group, and treatment A, B, C groups but not in control group. Model group received no treatment, but treatment A, B, C groups were treated with external application of the concentration of 0.1%, 0.2% and 0.4% of the pseudolaric acid for the lesions of ear skin. And the weight gain and the swelling degree of the mice' ear were recorded, weight of thymus and spleen were measured. Spleen suspension was prepared to test T lymphocyte and B lymphocyte levels of mice in five groups. Changes in serum IFN-gamma, IL-4 and IL-10 levels were tested through the enzyme linked immunosorbent assay (ELISA). RESULTS: The weight gain of mice in model group were significant lower than those of mice in the control group and the treatment A, B, C groups (P < 0.05). Weight gain of mice in treatment A, B groups were significant lower than that of control group (P < 0.05), but the difference in weight gain between treatment C group and control group showed no significant difference (P > 0.05). The swelling degree and the weight of mice ears in model group were significant higher than those of mice in control group and treatment A, B, C groups (P < 0.05). Swelling degree and the weight of mice ears of treatment A, B, C groups were obviously higher than that of control group (P < 0.05). The swelling degree and weight of mice' ears in treatment A, B, C groups were decreased with the increase of the drug dosage, but comparison between A, B and C group showed statistically differences (P < 0.05). The thymus and spleen index of mice in model group were significant higher than those of the other four groups (P < 0.05), among the four groups, thymus and spleen index of treatment A and B group were higher than control group and treatment C group (P < 0.05). The stimulation index of T and B cells of mice in model group was significantly higher than the rest four groups (P < 0.05). The serum IFN-gamma level of mice in control group and treatment A, B and C group was obviously lower than that of mice in model group (P < 0.05). The serum IFN-gamma level of mice in treatment A, B and C group were decreased with the increasing of the drug dosage, and the level of C group was obviously lower than that of A and B group (P < 0.05). CONCLUSION: The pseudolaric acid has anti-inflammation and immune adjustment the effects showing a remarkable therapeutic effects for the ACD mice. PMID- 27393096 TI - Influence on radiosensitivity of lung glandular cancer cells when ERCC1 gene silenced by targeted siRNA. AB - OBJECTIVE: To identify the influence on radiosensitivity of lung glandular cancer cells when excisions repair cross-complementing group1 (ERCC1) gene was silenced by targeted siRNA. METHODS: siRNA which targeting to ERCC1 and control siRNA was designed and synthesized. The human lung glandular cancer SPC-A-1 cells was transfected. A total of 56 nude mice were divided into two groups, and two kinds of SPC-A-1 cells were transplanted to armpit of right forelimb, to establish the nude mice subcutaneous xenotransplanted tumor model of human lung glandular cancer cells. After the tumor was developed, the nude mice were randomly divided into four groups and accepted different doses of X-Ray radiation, then the change of tumor volume, survival time of mice in every group were recorded and the average lifetime was calculated. Twenty-one days later of X-ray experiment, two mice were taken and killed in each group and the tumors organizations were stripped. The cell apoptosis rate and cell cycle distributions were obtained by FCM (flow cytometry). RESULTS: The volume of tumor which ERCC1 gene was silenced was less than single irradiation group after X-ray irradiation, and the growth speed was slower and the lifetime of mice was lengthened as well (P < 0.05). The cells apoptosis rate and the rate of G2/M cells which ERCC1 gene was silenced were higher than the same dose control group and the rate of G1 cells were lower, which indicated that the cells could be stopped at G2/M point, the cell proliferation was inhibited, the cell apoptosis was promoted and the radiation sensitivity was improved after the ERCC1 was silenced. CONCLUSIONS: The radiation sensitivity of lung glandular tumor could be improved after the ERCC1 gene was silenced by siRNA. PMID- 27393097 TI - Effects of arteannuin B, arteannuic acid and scopoletin on pharmacokinetics of artemisinin in mice. AB - OBJECTIVE: To explore the effects of arteannuin B, arteannuic acid and scopoletin on the pharmacokinetics of artemisinin in mice. METHODS: Artemisinin and a combination of artemisinin, arteannuin B, arteannuic acid and scopoletin were administered together to mice via oral administration. Blood samples were collected at different time intervals and pretreated by liquid-liquid extraction. The contents of four compounds in mouse plasma were determined by a validated HPLC-MS/MS method. RESULTS: Compared to single artemisinin group, the Cmax values from the combination group rose from 947 ng/mL to 1254 ng/mL. AUC(0-t) (2371 h ng/mL) was significantly higher than that from single artemisinin group (747 h ng/mL). The peak time lag and the CL values reduced at a proportion of 66%. CONCLUTIONS: Arteannuin B, arteannuic acid and scopoletin can markedly affect the pharmacokinetics of artemisinin. PMID- 27393098 TI - Study on the effect and mechanism of the dysfunction of CD4(+) T cells in the disease process of chronic cardiac failure. AB - OBJECTIVE: To study the effect and mechanism of the dysfunction of CD4(+) T cells in the disease process of chronic cardiac failure (CHF). METHODS: According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function III-IV group and heart function I-II group, event group and non-event group, and 50 healthy volunteers were included in the control group. Real-time PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-gamma, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. RESULTS: As compared to the control group, the transcription factors T bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-gamma, cytokines IL-17, T-bet/GATA-3, IFN-gamma/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart function III-IV group and heart function I-II group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL-4, Treg cells ratio, cytokines IL-10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function III-IV group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-gamma and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. CONCLUSIONS: There was a correlation between CHF and the dysfunction of CD4(+) T cells showing immune activation phenomenons of deviations from the Th1/Th2 balance towards Th1 and from the Th17/Treg balance towards Th17, which was also related to the types, severity and prognosis of the disease. PMID- 27393099 TI - Perfusion of gastrodin in abdominal aorta for alleviating spinal cord ischemia reperfusion injury. AB - OBJECTIVE: To observe the effects of perfusion of the gastrodin in abdominal aorta for alleviating the spinal cord ischemia reperfusion injury (SCIRI). METHODS: A total of 36 New Zealand white rabbits were divided randomly into sham operated group (group S), control group (group C) and gastrodin group (group G), 12 rabbits for each group. Aorta abdominalis infrarenalis blocking method was applied to establish the SCIRI model. The changes of motor evoked potentials (MEPs) before the ischemia and on 30 min, 60 min, 6 h, 12 h and 24 h of reperfusion of the gastrodin were respectively recorded, and the neurologic function score before the ischemia, on the 6 h, 12 h and 24 h of the reperfusion of the gastrodin were assessed. And the changes of the concentration of serum neuron specific enolase (NSE), interleukin (IL)-lbeta and IL-8 were measured before the ischemia, after 45 min of ischemia, and on 30 min, 60 min, 6 h, 12 h and 24 h of reperfusion of gastrodin. Then the levels of spinal cord nerve cells mitochondrial superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total antioxidant capacity (T-AOC) and mitochondrial swelling degree (MSD) were tested and the histopathologic changes in spinal cord tissues were observed. RESULTS: The levels of the NSE, IL-lbeta, IL-8, ROS, MDA and MSD of group C were all significantly elevated after the ischemia (P < 0.01); the levels of the spinal nerve cell mitochondria SOD, GSH-PX and T-AOC were all significantly reduced (P < 0.01), MEPs and spinal cord tissue pathology were damaged significantly (P < 0.01). The rate of motor neuron abnormalities and the damages of spinal cord tissue pathology of group G were significantly milder than those of group C (P < 0.01); the levels of NSE, IL-lbeta, IL-8, ROS, MDA and MSD were significantly lower than those of group C (P < 0.01), but the levels of SOD, GSH-PX and T-AOC were all significantly higher than those of group C (P < 0.01), and the recovery of neurologic function score during the reperfusion of gastrodin was significantly faster than group C (P < 0.01). CONCLUSIONS: Perfusion of the gastrodin in abdominal aorta can alleviate the spinal cord ischemia reperfusion injury by promoting the mitochondrial antioxidant capacity and inhibiting the inflammatory reaction. PMID- 27393100 TI - Ultrasonic diagnosis of patients with clonorchiasis and preliminary study of pathogenic mechanism. AB - OBJECTIVE: To discuss the liver function damage mechanism of patients with clonorchiasis by analyzing the ultrasound characteristics, liver function, change of the serum inflammatory factors and cell apoptosis factors. METHODS: Color Doppler ultrasound technique was adopted to detect the portal vein and blood flow change of patients with clonorchiasis; ELISA was used to determine the level of different serum inflammatory factors. The levels of serum total bilirubin, serum albumin and glutamic-pyruvic transaminase were detected by automatic biochemical analyzer. Western blot was used to determine the expression of proteins relevant to apoptosis. RESULTS: Compared with the health control group, the trunk diameter of portal vein and the thickness of spleen, as well as the hepatic artery pulsation index of clonorchiasis patients increased obviously, the mean blood flow velocity of portal vein (P < 0.05 or P < 0.01) decreased. The content of total bilirubin and transaminase in plasma increased significantly, but albumin decreased (P < 0.05). Levels of TNF-alpha, IL-6 and IFN-gamma increased remarkably, and the level of every factor was significantly different among patients with Child-Pugh , Child-Pugh II and Child-Pugh III classification of liver function (P < 0.05 or P < 0.01). With the exacerbation of liver dysfunction, levels of TNF-alpha, IL-6 and IFN-gamma gradually increased (P < 0.05). Compared with the healthy control group, the expression quantity of apoptosis protein Fas, FasL, Bax and Caspase-3 increased significantly (P < 0.05 or P < 0.01), but Bcl-2 decreased (P < 0.05). CONCLUSIONS: Changes of ultrasonic characteristics and liver dysfunction, caused by liver fluke infection, may be related to that both inflammatory response and apoptosis response have participated in the pathogenic process and liver damage course of clonorchiasis. PMID- 27393101 TI - Experimental study on the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice. AB - OBJECTIVE: To study the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice. METHODS: BALB/c mice were selected as experimental animals, ovarian cancer SKOV-3 cells transfected with miR-106a inhibitor and its negative control were inoculated subcutaneously, intratumoral injection of miR-106a inhibitor and its negative control were continued after tumor formation, and they were enrolled as treatment group and model group, respectively. Tumor volume and weight as well as Ki-67 and programmed cell death 4 (PDCD4) expression were determined; miR-106a inhibitor and its negative control as well as miR-106a mimic and its negative control were transfected into SKOV-3 cells, and expression of PDCD4 in cells was determined. RESULTS: Tumor tissue volume and weight as well as mRNA expression and protein expression of Ki-67 in treatment group were significantly lower than those in the model group while mRNA expression and protein expression of PDCD4 were significantly higher than those in the model group; transfection of miR-106a mimic could decrease mRNA expression and protein expression of PDCD4 in SKOV-3 cells, and transfection of miR-106a inhibitor could increase mRNA expression and protein expression of PDCD4 in SKOV 3 cells. CONCLUSIONS: Transfection of miR-106a inhibitor can inhibit the growth of tumor in ovarian cancer xenografts mice through increasing the expression of PDCD4. PMID- 27393102 TI - Effect of partial splenic embolization on the immune function of cirrhosis patients with hypersplenism. AB - OBJECTIVE: To discover the effect of partial splenic embolization on the immune function of cirrhotic patients with hypersplenism. METHODS: Patients involved in the study were enrolled and divided into three groups, including control group, experimental group, and complication group. Numbers of CD3(+), CD4(+) and CD8(+) T cells and CD4(+)CD25(+)CDl27(low/-) Treg cells in the peripheral blood of patients before surgery, 1 month, 6 months, 1 year, and 2 years after surgery were analyzed by fluorescence active cell sorting (FACS). Contents of immunoglobulins (IgA, IgG and IgM) were analyzed by auto immunoassay analyzer. RESULTS: In the peripheral blood of patients from experimental group, numbers of CD3(+), CD4(+) and CD8(+) T cells initially declined, but afterwards increased to normal level; in the peripheral blood of patients from complication group, CD3(+) and CD8(+) T cells showed the same trend, but the number of CD4(+) T cells was below normal level at all detection times. Furthermore, CD3(+), CD4(+) and CD8(+) T cells in the peripheral blood of patients from complication group were initially less than those in experimental group, and afterwards were comparable between two groups. In patients from both experimental group and complication group, the number of CD4(+) CD25(+) CDl27(low/-)Treg cells increased 1 month and 6 months after surgery, and gradually restored to normal level. CD4(+)CD25(+)CDl27(low/-) Treg cell counts in patients from complication group were initially more than those in patients from experimental group 1 month and 6 months after surgery, but then they were comparable. Furthermore, contents of immunoglobulins (IgA, IgG and IgM) were comparable in three groups at all detection times. CONCLUSION: Partial splenic embolization influenced the immune function of cirrhotic patients with hypersplenism in the short term but the immune function could afterwards gradually restore to normal. Our results implicated that measures that prevent infection and improve immune function were necessary in early stage after undergoing PSE in order to reduce complications. PMID- 27393103 TI - The protective effect and underlying mechanism of Hainan papaya water extract against neuronal apoptosis induced by Abeta40. AB - OBJECTIVE: To investigate whether Hainan papayas has protective effects in an Abeta40-induced primary neuron injury model and elucidate the underlying molecular mechanism. METHODS: Cultured primary neurons from the dorsal root ganglia (DRG) of Sprague-Dawley (SD) rats were treated with 20 MUM Abeta40 peptide, 100 MUg/L Hainan papaya water extract, peptide plus extract, or culture medium for 24 h. Cell viability was measured by MTT assay, and neuronal apoptosis was evaluated by DAPI staining. ERK signaling pathway-associated molecule activation and changes in Bax expression were analyzed by Western blotting and immunofluorescence. RESULTS: A cell viability rate of (44.11 +/- 6.59)% in the Abeta40 group was rescued to (79.13 +/- 6.64)% by adding different concentrations of the extract. DAPI showed pyknotic nuclei in 39.5% of Abeta40-treated cells; the fraction dropped to 17.4% in the 100 MUg/L extract group. ERK phosphorylation was observed in the Abeta40 group but was ameliorated by pretreatment with 100 MUg/L extract. Hainan papaya water extract also prevented Abeta40-induced phosphorylation of MEK, RSK1 and CREB associated with ERK signaling and downregulated Bax expression in the neurons. CONCLUSION: The results suggest that Hainan papaya water extract has protective effects on neurons; the mechanism may be related to suppression of ERK signaling activation. PMID- 27393104 TI - Clinical significance of skin rash in dengue fever: A focus on discomfort, complications, and disease outcome. AB - OBJECTIVES: To assess whether the cutaneous features in patients with dengue fever are associated with abnormal blood biochemistry, complications, and poor disease outcome. METHODS: Forty five patients with dengue fever were identified at a medical center in Kaohsiung, Taiwan, from September to November 2014. All cases were exclusively caused by type 1 dengue virus. Patients were classified into two groups, based on the presence or absence of skin rash, and their rash was subclassified into maculopapular, morbilliform, and petechial types. Clinical symptoms, laboratory data, disease outcome, and complications were compared between the two groups. RESULTS: Thirty two patients with dengue fever developed skin rash (SP group, n = 32) while the rest of 13 did not (SN group, n = 13). The patient numbers in the maculopapular, morbilliform, and petechial group were 4, 21, and 7, respectively. The SP group was younger (P = 0.001), experienced more pruritus (P = 0.008) and more swollen palms/soles (P = 0.015) than the SN group. However, the SN group had greater genital mucosa involvement (P = 0.008), higher platelet transfusion rate (P = 0.003), and lower hemoglobin and hematocrit levels (P = 0.030) than the SP group. Patients with morbilliform lesions had a higher incidence of palm/sole swelling, less genital mucosal involvement, and a lower platelet transfusion rate than did patients with maculopapular or petechial lesions. CONCLUSIONS: Cutaneous manifestations provide an important clue to dengue fever. In patients with dengue fever, those with skin rash tend to have itching and swelling of the palms/soles, however, those without skin rash tend to have more complications and poor disease outcomes. PMID- 27393105 TI - Predicted pattern of Zika virus infection distribution with reference to rainfall in Thailand. AB - Zika virus infection is the present global medical problem. The disease appears in several countries around the world. The relationship between rainfall and occurrence of Zika virus infection was previously mentioned. Here, the authors use the mathematical modeling technique to reappraise on the previous data on immunoreactivity rate of Zika virus, dengue virus and Ckikungunya virus in Thailand and the reported interrelationship between arboviral infections and rainfall in Thailand for constructing of the predicted pattern of Zika virus distribution in Thailand. This data can be a useful tool for further disease surveillance in this area. PMID- 27393106 TI - Humidity that is appropriate for Zika virus infection: A summary from Thai cases. PMID- 27393107 TI - A Response to Keller's Commentary. PMID- 27393108 TI - [Not Available]. PMID- 27393109 TI - [Not Available]. PMID- 27393110 TI - [Not Available]. PMID- 27393111 TI - [Not Available]. PMID- 27393112 TI - [Not Available]. PMID- 27393113 TI - [Not Available]. PMID- 27393114 TI - [Not Available]. PMID- 27393115 TI - The role of polymyography in the treatment of cervical dystonia: the authors reply. PMID- 27393116 TI - Olfaction as a marker for depression. AB - Olfactory and emotional higher processing pathways share common anatomical substrates. Hence, depression is often accompanied by alterations in olfactory function. These alterations are negative in nature and may involve decreased activation in olfactory eloquent structures or decreased volume in the olfactory bulb (OB). We suggest that olfaction and depression interact in two ways. First, olfactory function in depression is impaired as a consequence of reduced olfactory attention and diminished olfactory receptor turnover rates. Second, the OB may constitute a marker for enhanced vulnerability to depression. Closer analysis of these interactions may help to explain observed experimental data, as well as to elucidate new therapeutic strategies involving olfaction. Because of the difficulties to disentangle cause from consequence in the relationship between olfaction and depression, longitudinal and intervention studies are necessary to elucidate this further. PMID- 27393117 TI - Development of the multiple sclerosis (MS) early mobility impairment questionnaire (EMIQ). AB - The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundant items which were removed leading to the final nine-item EMIQ. The nine-item EMIQ performed well with respect to: test-retest reliability (ICC = 0.858); internal consistency (alpha = 0.893); convergent validity; and known-groups methods for construct validity. A cut-point of 41 on the 0-to-100 scale resulted in sufficient sensitivity and specificity statistics for viably identifying patients with mobility impairment. The EMIQ is a content valid and psychometrically sound instrument for capturing MS patients' experience with mobility impairments in a clinical practice setting. Additional research is suggested to further confirm the EMIQ's screening properties over time. PMID- 27393118 TI - The heterozygous A53T mutation in the alpha-synuclein gene in a Chinese Han patient with Parkinson disease: case report and literature review. AB - The missense mutation A53T of alpha-synuclein gene (SNCA) was reported to be a rare but definite cause of sporadic and familial Parkinson disease (PD). It seemed to be restricted geographically in Greece and Italy. We aimed to identify the SNCA mutations in a Chinese PD cohort. Ninety-one early onset PD patients or familial PD probands were collected consecutively for the screening of PD-related genes. The genetic analysis was carried out by target sequencing of the exons and the corresponding flanking regions of the PD-related genes using Illumina HiSeq 2000 sequencer and further confirmed by Sanger sequencing or restriction fragment length polymorphism. Dosage mutations of exons in these genes were carried out by multiple ligation-dependent probe amplification. Among the 91 patients, we found only one heterozygous mutation of SNCA A53T, in a 23-year-old male patient with negative family history. The [(11)C]-2beta-carbomethoxy-3beta-(4-fluorophenyl) tropan (CFT) PET and PD-related spatial covariance pattern (PDRP) via [(18)F] fluorodeoxyglucos (FDG) PET confirmed a typical pattern of PD. After examining his parents, we found his mother was an asymptomatic carrier, with declined hand dexterity detected by quantitative motor tests. Reduced dopamine transporter uptake of his mother was identified by CFT PET, and abnormal PDRP pattern was found by FDG PET. Our investigation expanded the clinical and genetic spectrum of Chinese PD patients, and we suggested SNCA mutations to be screened in familial and early onset Chinese PD patients. PMID- 27393120 TI - Perfluoroalkyl acids (PFAAs) in indoor and outdoor dusts around a mega fluorochemical industrial park in China: Implications for human exposure. AB - The manufacture of fluorochemicals can lead to high levels of perfluoroalkyl acids (PFAAs) contaminating the surrounding environment and consequently elevated exposure to the local residents. In this study, measurements of PFAAs associated with indoor and outdoor dusts around a mega fluorochemical industrial park (FIP) were made. Perfluorooctanoic acid (PFOA) and short-chain perfluoroalkyl carboxylic acids (C4-C7 PFCAs) were the predominant forms in all samples. The signature of the PFAAs in dusts in the local area matched that found within the FIP complex. The contamination plume in the local area could be linked to the prevailing wind direction starting from the FIP. The dust concentrations decreased exponentially with distance from the FIP (noticeably in the first 5km). PFAAs contamination could be detected at the furthest location, 20km away from the FIP. The concentrations of PFAAs were higher in indoor dust (73-13,500ng/g, median: 979ng/g) than those in outdoor dust (5-9495ng/g, median: 62ng/g) at every location. The highest estimated daily intake of PFOA via dust ingestion (26.0ng/kg.bw/day) was for toddlers (2-5years) living 2km away from the FIP, which is posing human health risk, though exposure remains within the provisional tolerable daily intake values. PMID- 27393121 TI - New measures to capture end of life concerns in Huntington disease: Meaning and Purpose and Concern with Death and Dying from HDQLIFE (a patient-reported outcomes measurement system). AB - PURPOSE: Huntington disease (HD) is an incurable terminal disease. Thus, end of life (EOL) concerns are common in these individuals. A quantitative measure of EOL concerns in HD would enable a better understanding of how these concerns impact health-related quality of life. Therefore, we developed new measures of EOL for use in HD. METHODS: An EOL item pool of 45 items was field tested in 507 individuals with prodromal or manifest HD. Exploratory and confirmatory factor analyses (EFA and CFA, respectively) were conducted to establish unidimensional item pools. Item response theory (IRT) and differential item functioning analyses were applied to the identified unidimensional item pools to select the final items. RESULTS: EFA and CFA supported two separate unidimensional sets of items: Concern with Death and Dying (16 items), and Meaning and Purpose (14 items). IRT and DIF supported the retention of 12 Concern with Death and Dying items and 4 Meaning and Purpose items. IRT data supported the development of both a computer adaptive test (CAT) and a 6-item, static short form for Concern with Death and Dying. CONCLUSION: The HDQLIFE Concern with Death and Dying CAT and corresponding 6-item short form, and the 4-item calibrated HDQLIFE Meaning and Purpose scale demonstrate excellent psychometric properties. These new measures have the potential to provide clinically meaningful information about end-of-life preferences and concerns to clinicians and researchers working with individuals with HD. In addition, these measures may also be relevant and useful for other terminal conditions. PMID- 27393122 TI - Integrating the escalation and dose expansion studies into a unified Phase I clinical trial. AB - We focus on Phase I dose finding studies as they are currently undertaken. The design and analysis of these trials have changed over the last years and, in particular, it is now rare for a Phase I study to not include one or more dose expansion cohorts (DEC). It is common to see DEC involving several hundred patients, building on an initial dose escalation study that may have no >20 to 30 patients. There has been recent focus by researchers on the design of DEC and the analysis of DEC data. It is reasonable to explicitly account for the uncertainty in the estimation of the MTD, the dose upon which the whole of the DEC is currently based. In this paper, we focus on the dose escalation phase prior to the DEC, with the purpose of adapting it to the needs of DEC. Specifically, before beginning the DEC phase, we need to identify those dose levels that will be taken into the DEC. We define a useful concept for this purpose, the co-MTD, and the results support that the estimated MTD and co-MTD contain the true MTD with high probability. We also provide stopping rules for when the data support that the dose escalation can end and the dose expansion can begin. Simulated trials support the use of the proposed approach and provide additional information on how this approach compares with current practice. PMID- 27393123 TI - Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-beta-D-glucan, Aspergillus PCR, multifungal DNA microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of a prospective multicentre study. AB - High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immunocompromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-beta-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n=3), probable (n=34), possible (n=33), and no IFD (n=29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach. PMID- 27393119 TI - Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs. AB - Sphingolipids (SPs) comprise a highly diverse class of lipids that serve biological roles both as structural components of cell membranes and as mediators of cell signaling. Pharmacologic and genetic manipulation of SPs and their signaling systems have underscored their importance in most biological processes, including central nervous system development and function. Likewise, perturbations of SP accumulation or signaling have been associated with a number of disease states, such as neural tube defects, neuroinflammation, stroke, and dementia. SPs can be endogenously synthesized de novo, and their metabolism is a well-regulated process, so their value as nutraceuticals has not been scrutinized. However, there is evidence that sphingolipid-rich diets can affect lipid homeostasis, and several mycotoxins are SP analogs that are known to cause profound derangement of SP metabolism or signaling. Furthermore, plants and invertebrates have SP species that are not present in mammals. Several of these have been shown to induce biological responses in mammalian cells. These findings suggest that dietary intake of SPs or SP analogs may have significant effects on human health or disease outcome. This manuscript provides an overview of SP metabolism and signaling, their perturbations in neurological diseases, as well as potential impacts of modulating this system in the brain. PMID- 27393124 TI - Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain. AB - Host cell invasion is a major feature of Staphylococcus aureus and contributes to infection development. The intracellular metabolically active bacteria can induce host cell activation and death but they can also persist for long time periods. In this study a comparative analysis was performed of different well characterized S. aureus strains in their interaction with a variety of host cell types. Staphylococcus aureus (strains 6850, USA300, LS1, SH1000, Cowan1) invasion was compared in different human cell types (epithelial and endothelial cells, keratinocytes, fibroblasts, osteoblasts). The number of intracellular bacteria was determined, cell inflammation was investigated, as well as cell death and phagosomal escape of bacteria. To explain strain-dependent differences in the secretome, a proteomic approach was used. Barrier cells took up high amounts of bacteria and were killed by aggressive strains. These strains expressed high levels of toxins, and possessed the ability to escape from phagolysosomes. Osteoblasts and keratinocytes ingested less bacteria, and were not killed, even though the primary osteoblasts were strongly activated by S. aureus. In all cell types S. aureus was able to persist. Strong differences in uptake, cytotoxicity, and inflammatory response were observed between primary cells and their corresponding cell lines, demonstrating that cell lines reflect only partially the functions and physiology of primary cells. This study provides a contribution for a better understanding of the pathomechanisms of S. aureus infections. The proteomic data provide important basic knowledge on strains commonly used in the analysis of S. aureus-host cell interaction. PMID- 27393125 TI - Potential arms race in the coevolution of primates and angiosperms: brazzein sweet proteins and gorilla taste receptors. AB - OBJECTIVES: We explored whether variation in the sweet taste receptor protein T1R3 in primates could contribute to differences in sweet taste repertoire among species, potentially reflecting coevolution with local plants. Specifically, we examined which primates are likely to be sweet "tasters" of brazzein, a protein found in the fruit of the African plant Pentadiplandra brazzeana that tastes intensely sweet to humans, but provides little energy. Sweet proteins like brazzein are thought to mimic the taste of sugars to entice seed dispersers. We examined the evolution of T1R3 and assessed whether primates are likely "deceived" by such biochemical mimicry. METHODS: Using published and new sequence data for TAS1R3, we characterized 57 primates and other mammals at the two amino acid sites necessary to taste brazzein to determine which species are tasters. We further used dN/dS-based methods to look for statistical evidence of accelerated evolution in this protein across primate lineages. RESULTS: The taster genotype is shared across most catarrhines, suggesting that most African primates can be "tricked" into eating and dispersing P. brazzeana's seeds for little caloric gain. Western gorillas (Gorilla gorilla), however, exhibit derived mutations at the two brazzein-critical positions, and although fruit is a substantial portion of the western gorilla diet, they have not been observed to eat P. brazzeana. Our analyses of protein evolution found no signature of positive selection on TAS1R3 along the gorilla lineage. DISCUSSION: We propose that the gorilla-specific mutations at the TAS1R3 locus encoding T1R3 could be a counter-adaptation to the false sweet signal of brazzein. PMID- 27393127 TI - [Not Available]. PMID- 27393126 TI - Preventing Scars after Injury with Partial Irreversible Electroporation. AB - Preventing the formation of hypertrophic scars, especially those that are a result of major trauma or burns, would have enormous impact in the fields of regenerative and trauma medicine. In this report, we introduce a noninvasive method to prevent scarring based on nonthermal partial irreversible electroporation. Contact burn injuries in rats were treated with varying treatment parameters to optimize the treatment protocol. Scar surface area and structural properties of the scar were assessed with histology and non-invasive, longitudinal imaging with polarization-sensitive optical coherence tomography. We found that partial irreversible electroporation using 200 pulses of 250 V and 70 MUs duration, delivered at 3 Hz every 20 days during a total of five therapy sessions after the initial burn injury, resulted in a 57.9% reduction of the scar area compared with untreated scars and structural features approaching those of normal skin. Unlike humans, rats do not develop hypertrophic scars. Therefore, the use of a rat animal model is the limiting factor of this work. PMID- 27393128 TI - [Not Available]. AB - Pharmacoepidemiological studies exploring utilisation of psychotropic medications in real-life conditions are required to identify extension of indications, since the risk of gap between the theoretical target population and the population actually treated is especially marked for this class of drugs. A large proportion of subjects from the general population are exposed to psychotropic medications, so even a small increase in the risk of adverse effect may have major deleterious consequences for the health of the general population. Hence, pharmacoepidemiological studies are also required to explore the risk/benefit ratio of these drugs in real-life conditions. These studies may provide answers to currently unsolved public health questions, such as the long-term cognitive impact of exposure to benzodiazepines, the impact of antidepressant on suicidal behaviour, or the risks associated with enlarged use of antipsychotics. Only findings obtained by such studies may allow risk management and elaboration of guidelines based upon factual data. PMID- 27393129 TI - Interaction entre le paracetamol et la fluindione : a propos d'un cas. PMID- 27393130 TI - [Not Available]. PMID- 27393134 TI - Introducing a fund for open-access fees. PMID- 27393133 TI - Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response. AB - Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor-specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen presenting cells. Bilirubin was administered intraperitoneally before pancreatic procurement or was added to culture media after islet isolation in AJ mice. Islets were exposed to transplant-associated nutrient deprivation and hypoxia. Bilirubin significantly decreased islet cell death after isolation and hypoxic stress. Bilirubin supplementation of islet media also decreased the release of DAMPs (HMGB1), inflammatory cytokines (IL-1beta and IL-6), and chemokines (MCP 1). Cytoprotection was mediated by the antioxidant effects of bilirubin. Treatment of macrophages with bilirubin induced a regulatory phenotype, with increased expression of PD-L1. Coculture of these macrophages with splenocytes led to expansion of Foxp3+ Tregs. In conclusion, exogenous bilirubin supplementation showed cytoprotective and antioxidant effects in a relevant model of islet isolation and hypoxic stress. Suppression of DAMP release, alterations in cytokine profiles, and tolerogenic effects on macrophages suggest that the use of this natural antioxidant may provide a method of preconditioning to improve outcomes after allograft transplantation. PMID- 27393136 TI - A novel validated model for the prediction of insulin therapy initiation and adverse perinatal outcomes in women with gestational diabetes mellitus. AB - AIMS/HYPOTHESIS: Identifying women with gestational diabetes mellitus who are more likely to require insulin therapy vs medical nutrition therapy (MNT) alone would allow risk stratification and early triage to be incorporated into risk based models of care. The aim of this study was to develop and validate a model to predict therapy type (MNT or MNT plus insulin [MNT+I]) for women with gestational diabetes mellitus (GDM). METHODS: Analysis was performed of de identified prospectively collected data (1992-2015) from women diagnosed with GDM by criteria in place since 1991 and formally adopted and promulgated as part of the more detailed 1998 Australasian Diabetes in Pregnancy Society management guidelines. Clinically relevant variables predictive of insulin therapy by univariate analysis were dichotomised and included in a multivariable regression model. The model was tested in a separate clinic population. RESULTS: In 3317 women, seven dichotomised significant independent predictors of insulin therapy were maternal age >30 years, family history of diabetes, pre-pregnancy obesity (BMI >=30 kg/m(2)), prior GDM, early diagnosis of GDM (<24 weeks gestation), fasting venous blood glucose level (>=5.3 mmol/l) and HbA1c at GDM diagnosis >=5.5% (>=37 mmol/mol). The requirement for MNT+I could be estimated according to the number of predictors present: 85.7-93.1% of women with 6-7 predictors required MNT+I compared with 9.3-14.7% of women with 0-1 predictors. This model predicted the likelihood of several adverse outcomes, including Caesarean delivery, early delivery, large for gestational age and an abnormal postpartum OGTT. The model was validated in a separate clinic population. CONCLUSIONS/INTERPRETATION: This validated model has been shown to predict therapy type and the likelihood of several adverse perinatal outcomes in women with GDM. PMID- 27393135 TI - Effects of exercise training on intrahepatic lipid content in humans. AB - Non-alcoholic fatty liver (NAFL) is the most common liver disorder in western society. Various factors may play a role in determining hepatic fat content, such as delivery of lipids to the liver, de novo lipogenesis, hepatic lipid oxidation, secretion of intrahepatic lipids to the circulation or a combination of these. If delivery of lipids to the liver outweighs the sum of hepatic lipid oxidation and secretion, the intrahepatic lipid (IHL) content starts to increase and NAFL may develop. NAFL is closely related to obesity and insulin resistance and a fatty liver increases the vulnerability to type 2 diabetes development. Exercise training is a cornerstone in the treatment and prevention of type 2 diabetes. There is a large body of literature describing the beneficial metabolic consequences of exercise training on skeletal muscle metabolism. Recent studies have started to investigate the effects of exercise training on liver metabolism but data is still limited. Here, first, we briefly discuss the routes by which IHL content is modulated. Second, we review whether and how these contributing routes might be modulated by long-term exercise training. Third, we focus on the effects of acute exercise on IHL metabolism, since exercise also might affect hepatic metabolism in the physically active state. This will give insight into whether the effect of exercise training on IHL could be explained by the accumulated effect of acute bouts of exercise, or whether adaptations might occur only after long-term exercise training. The primary focus of this review will be on observations made in humans. Where human data is missing, data obtained from well-accepted animal models will be used. PMID- 27393137 TI - The S20G substitution in hIAPP is more amyloidogenic and cytotoxic than wild-type hIAPP in mouse islets. AB - AIMS/HYPOTHESIS: The S20G human islet amyloid polypeptide (hIAPP) substitution is associated with an earlier onset of type 2 diabetes in humans. Studies of synthetic S20G hIAPP in cell-free systems and immortalised beta cells have suggested that this may be due to increased hIAPP amyloidogenicity and cytotoxicity. Thus, using primary islets from mice with endogenous S20G hIAPP expression, we sought to determine whether the S20G gene mutation leads to increased amyloid-induced toxicity, beta cell loss and reduced beta cell function. METHODS: Islets from mice in which mouse Iapp was replaced with human wild-type or S20G hIAPP were isolated and cultured in vitro under amyloid-forming conditions. Levels of insulin and hIAPP mRNA and protein, amyloid deposition and beta cell apoptosis and area, as well as glucose-stimulated insulin and hIAPP secretion, were quantified. RESULTS: Islets expressing S20G hIAPP cultured in 16.7 mmol/l glucose demonstrated increased amyloid deposition and beta cell apoptosis, reduced beta cell area, decreased insulin content and diminished glucose-stimulated insulin secretion, compared with islets expressing wild-type hIAPP. Amyloid deposition and beta cell apoptosis were also increased when S20G islets were cultured in 11.1 mmol/l glucose (the concentration that is thought to be physiological for mouse islets). CONCLUSIONS/INTERPRETATION: S20G hIAPP reduces beta cell number and function, thereby possibly explaining the earlier onset of type 2 diabetes in individuals carrying this gene mutation. PMID- 27393138 TI - Martelella suaedae sp. nov. and Martelella limonii sp. nov., isolated from the root of halophytes. AB - Two Gram-stain-negative, aerobic and endophytic bacterial strains, designated YC7033T and YC7034T, were isolated from the roots of halophytes (Suaeda maritime and Limonium tetragonum, respectively) inhabiting tidal flats of the Sacheon area, Korea. The phylogenetic analyses of 16S rRNA gene sequences showed that the two strains were closely related to Martelella endophytica YC6887T, Martelella mangrovi BM9-1T, Martelella radicis BM5-7T and Martelella mediterranea DSM 17316T at 97.6-99.1 % similarity. Sequence similarities with the type strains of another closely related genus, Rhizobium, were lower than 95.0 %. Both strains contained ubiquinone-10 (Q-10) as the major respiratory quinone system. The G+C contents of the genomic DNA of strains YC7033T and YC7034T were 52.8 and 62.2 mol%, respectively. The major fatty acids of both strain YC7033T and strain YC7034T were summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C19 : 0 cyclo omega8c. On the basis of phylogenetic analysis, and biochemical and phenotypic characteristics, strains YC7033T and YC7034T represent two novel species of the genus Martelella, for which the names Martelella suaedae sp. nov. (type strain: YC7033T=KACC 17175T=NBRC 109440T) and Martelella limonii sp. nov. (type strain: YC7034T=KACC 17176T=NBRC 109441T) are proposed, respectively. PMID- 27393139 TI - Lithium in Paediatric Patients with Bipolar Disorder: Implications for Selection of Dosage Regimens via Population Pharmacokinetics/Pharmacodynamics. AB - BACKGROUND: Lithium is a well-established treatment for bipolar I disorder in adults. However, there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents. We aimed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients. METHODS: Lithium concentrations, Young Mania Rating Scale (YMRS) and Clinical Global Impressions Improvement (CGI-I) scores over 24 weeks were available from 61 paediatric patients with bipolar I disorder. The population pharmacokinetics/pharmacodynamics were co-modelled. Concentrations and clinical effects following several dosage regimens were predicted by Monte Carlo simulations. RESULTS: The pharmacokinetics were well characterised by a two compartment model with linear elimination. Including the effect of total body weight (TBW) or lean body weight (LBW) on clearance and volume of distribution decreased the unexplained inter-individual variability by up to 12 %. The population mean (inter-individual variability) clearance was 1.64 L/h/53 kg LBW0.75 (19 %) and central volume of distribution 23.6 L/53 kg LBW (6.8 %). The average lithium concentration over a dosing interval required for a 50 % reduction in YMRS was 0.711 mEq/L (59 %). A maintenance dose of 25 mg/kg TBW/day lithium carbonate in two daily doses was predicted to achieve a >=50 % reduction in YMRS in 74 % of patients, while ~8 % of patients would be expected to have trough concentrations above the nominal safety threshold of 1.4 mEq/L. Therefore, therapeutic drug monitoring will still be required even with these dosing strategies. CONCLUSIONS: When accounting for body size, the pharmacokinetic parameters in paediatric patients were within the range of estimates from adults. Pharmacokinetic/pharmacodynamic modelling supported development of practical scientifically-based dosage regimens for paediatric patients. PMID- 27393141 TI - [Grading of prostate cancer]. AB - The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system. PMID- 27393140 TI - Pharmacokinetics of Irinotecan, Oxaliplatin and 5-Fluorouracil During Hepatic Artery Chronomodulated Infusion: A Translational European OPTILIV Study. AB - The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined during the first course of chronomodulated triplet HAI in 11 patients and related to toxicities after one or three courses. Consistent trends were found between the area under the plasma concentration-time curve (AUC) values of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN38; a bioactive metabolite), total oxaliplatin and platinum ultrafiltrate (P-UF), on the one hand, and subsequent leukopenia severity, on the other hand. Moreover, the maximum plasma concentration (C max) and the AUC of P-UF significantly predicted grades of diarrhoea (p = 0.004 and 0.017, respectively) and anaemia (p = 0.001 and 0.008, respectively) after the first course. Systemic drug exposure helps explain both the adverse events and the low rate of extrahepatic progression-a usual drawback of HAI chemotherapy-thus supporting upfront testing of the regimen. Systems optimization of chronomodulated HAI delivery could further reduce adverse events. PMID- 27393142 TI - Idiopathic pulmonary fibrosis a rare disease with severe bone fragility. AB - Idiopathic pulmonary fibrosis (IPF) is a rare form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The aim of this cross sectional study was to assess the prevalence of osteoporosis and fragility fracture in a population of adults with IPF and to identify whether any possible clinical and pulmonary function parameters may be associated with increased bone fragility. In 58 IPF patients (mean age 65.1 +/- 9.1 years), we measured bone mineral density (BMD) of the lumbar spine, the femoral neck, and the entire hip. Moreover, the presence of vertebral fractures on a lateral chest X-ray study was evaluated, and a vertebral fracture burden was quantified using the spinal deformity index (SDI). As expected, osteoporosis was significantly more frequent in females with respect to males (57.9 vs 20.5 %, respectively), whereas the fractures prevailed in males with respect to females (38.5 vs 26.3 %, respectively). There were positive correlations between BMD at all skeletal sites and respiratory parameters; in particular for FVC % and DLCO % with BMD at femoral sub-regions. Moreover, we compared the average of DLCO (%) measure by values of SDI score that was higher in those patients with lower values of DLCO (%). The study shows a high prevalence of fragility with vertebral fractures in IPF patients, especially in males. Moreover, the vertebral fracture burden is associated with a worsening of FVC (%) and DLCO (%). Therefore, an evaluation of bone status is recommended, especially in those patients who are candidates for lung transplantation. PMID- 27393143 TI - Outcomes for a Public Hospital Tobacco Cessation Program: The Cook County Health and Hospitals System Experience. AB - The objective of this study is to determine the rate and predictors of sustained smoking cessation for a cohort of smokers exposed to a guideline-based health education program delivered during routine clinical care at an urban public hospital. This is a retrospective analysis of 755 public hospital system patients who had at least two health educator contacts embedded in routine clinical care, with the latter contact 12-18 months after the baseline. The education occurred during visits to primary care, specialty clinics, urgent/episodic care, or during hospitalization. The assessment of smoking status is determined by the health educators as part of their routine assessment and recorded in the program's database. The primary outcomes are self-reported 12-month sustained smoking cessation at the 12-18 month contact and predictors of cessation. The cohort is predominantly minority smokers (African American 69 % and Latino 15 %) and uninsured (70 %) or on Medicaid (13 %). The sustained cessation rate was 9.3 %. Latino ethnicity, smoking 1-9 cigarettes/day at baseline, reporting smoke-free home, and additional educator contact in the year after the baseline were independent predictors of sustained cessation in the multivariate analysis. Smokers with multiple risks for poor cessation outcomes exposed to a guideline based program of health education during routine healthcare encounters had sustained smoking cessation rates that compare favorably with published National Health Interview Study population cessation rates. An additional educator contact after the baseline was a predictor of cessation. The findings support development of cessation programs in which health educators are integrated into clinical care settings. PMID- 27393144 TI - Swaddling and Infant Sleeping Practices. AB - Swaddling promotes quiet sleep and may be a useful strategy to encourage infant safe sleep practices. We explored the effect of a swaddling education intervention on infant sleep practices in an urban minority community. We compared a cohort of postpartum mothers who were given education about swaddling to a historical group. Breastfeeding and pacifier use were similar in both groups. Compared to the historical group (n = 121), mothers in the swaddling group (n = 40) were more likely to swaddle infants to sleep (52.5 vs. 23.1 %, p = .001) and less likely to bedshare (15.4 vs. 33.1 %, p = .042). No significant effect was reported on infant supine sleep (81.6 vs. 69.4 %, p = .212). A postpartum swaddling education intervention had a limited impact on infant safe sleeping practices in an urban minority community. A recent metaanalysis demonstrated an increased risk of sudden infant death in infants swaddled for sleep and recommended the need to avoid the prone and side sleep position, especially for swaddled infants, and to set an age and developmentally appropriate limit for the use of swaddling. Ongoing studies are needed to monitor the safety and effectiveness of swaddling as a tool to promote safe sleeping in infants. PMID- 27393145 TI - Effect of mutations to amino acid A301 and F361 in thermostability and catalytic activity of the beta-galactosidase from Bacillus subtilis VTCC-DVN-12-01. AB - BACKGROUND: Beta-galactosidase (EC 3.2.1.23), a commercially important enzyme, catalyses the hydrolysis of beta-1,3- and beta-1,4-galactosyl bonds of polymer or oligosaccharidesas well as transglycosylation of beta-galactopyranosides. Due to catalytic properties; beta-galactosidase might be useful in the milk industry to hydrolyze lactose and produce prebiotic GOS. The purpose of this study is to characterize beta-galactosidase mutants from B. subtilis. RESULTS: Using error prone rolling circle amplification (epRCA) to characterize some random mutants of the beta-galactosidase (LacA) from B. subtilisVTCC-DVN-12-01, amino acid A301 and F361 has been demonstrated significantly effect on hydrolysis activity of LacA. Mutants A301V and F361Y had markedly reduced hydrolysis activity to 23.69 and 43.22 %, respectively. Mutants the site-saturation of A301 reduced catalysis efficiency of LacA to 20-50 %, while the substitution of F361 by difference amino acids (except tyrosine) lost all of enzymatic activity, indicating that A301 and F361 are important for the catalytic function. Interestingly, the mutant F361Y exhibited enhanced significantly thermostability of enzyme at 45-50 degrees C. At 45 degrees C, LacA-361Y retained over 93 % of its original activity for 48 h of incubation, whereas LacA-WT and LacA-301Vwere lost completely after 12 and 24 h of incubation, respectively. The half-life times of LacA-361Y and LacA-301 V were about 26.8 and 2.4 times higher, respectively, in comparison to the half life time of LacA-WT. At temperature optimum 50 degrees C, LacA-361Y shows more stable than LacA-WT and LacA-301 V, retaining 79.88 % of its original activities after 2 h of incubation, while the LacA-WT and LacA-301 V lost all essential activities. The half-life time of LacA-361Y was higher 12.7 and 9.39 times than that of LacA-WT and LacA-301 V, respectively. LacA-WT and mutant enzymes were stability at pH 5-9, retained over 90 % activity for 72 h of incubation at 30 degrees C. However, LacA-WT showed a little bit more stability than LacA-301 V and LacA-361Y at pH 4. CONCLUSIONS: Our findings demonstrated that the amino acids A301V and F361 play important role in hydrolysis activity of beta galactosidase from B. subtilis. Specially, amino acid F361 had noteworthy effect on both catalytic and thermostability of LacA enzyme, suggesting that F361 is responsible for functional requirement of the GH42 family. PMID- 27393147 TI - Erratum to: Why you may need a neurologist to see a comatose patient in the ICU. PMID- 27393148 TI - Overexpression of SpCBL6, a calcineurin B-like protein of Stipa purpurea, enhanced cold tolerance and reduced drought tolerance in transgenic Arabidopsis. AB - The purpose of the present study was to characterize SpCBL6 (GenBank accession number: KT780442) from Stipa purpurea and elucidate the function of this protein in abiotic stress. The full-length cDNA of SpCBL6 was isolated from S. purpurea by rapid amplification of cDNA ends methods. Laser confocal microscopy was used to analyze the subcellular localization of SpCBL6. The constructs of 35S:GFP SpCBL6 was used to transform wild-type (WT) Arabidopsis plants (ecotype Columbia 0) with the floral dip method. Quantitative reverse-transcription PCR (qRT-PCR), water potential, photosynthetic efficiency (F v/F m), and ion leakage was performed to investigate the role of SpCBL6 in abiotic stress. The open reading frame of SpCBL6 contains 681 bp nucleotides and encodes a 227-amino acid polypeptide. Phylogenetic analysis indicated that SpCBL6 showed the highest similarity with rice OsCBL6. SpCBL6 transcripts were induced by freezing and drought treatments. Subcellular localization analysis showed that SpCBL6 was located in membrane of protoplast. Overexpression of SpCBL6 in Arabidopsis thaliana demonstrated that the transgenic plants were more tolerant to cold treatment, but less tolerant to drought, compared with the plants. qRT-PCR analysis showed that the drought stress marker genes were inhibited in transgenic plants, whereas the cold stress marker genes were enhanced. Further analysis showed that SpCBL6-overexpressing plants showed enhanced water potential, photosynthetic efficiency (F v/F m), and reduced ion leakage compared with the wild-type after cold treatment. Collectively, these results indicate that SpCBL6, a new member of the CBL gene family isolated from S. purpurea, enhances cold tolerance and reduces drought tolerance in plants. PMID- 27393146 TI - Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells. AB - BACKGROUND: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5 hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. METHODS: Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years. RESULTS: We identified 10,685 frequently hydroxymethylated CpG sites in MSCs that were, as in other cell types, significantly associated with low density CpG regions, introns, the histone posttranslational modification H3k4me1 and enhancers. Study of the age-associated changes to 5hmC identified 785 hyper- and 846 hypo-hydroxymethylated CpG sites in the MSCs obtained from older individuals. CONCLUSIONS: DNA hyper-hydroxymethylation in the advanced-age group was associated with loss of 5mC, which suggests that, at specific CpG sites, this epigenetic modification might play a role in DNA methylation changes during lifetime. Since bone-marrow MSCs have many clinical applications, and the fact that the epigenomic alterations in this cell type associated with aging identified in this study could have associated functional effects, the age of donors should be taken into account in clinical settings. PMID- 27393149 TI - MiR-9 promotes osteoblast differentiation of mesenchymal stem cells by inhibiting DKK1 gene expression. AB - The aim of this study is to investigate the role of miR-9 and its mechanism on the osteoblast differentiation of mesenchymal stem cells. Real-time PCR and western blotting were used to study gene expression. Assay of Alkaline phosphatase activity and alizarin red staining were used to examine osteoblast differentiation. Transfection of miR-9 mimics or lent-shmiR-9 was used to modulate the level of miR-9 in C2C12. Overexpression of miR-9 in C2C12 cells stimulated alkaline phosphatase activity and osteoblast mineralization, as well as the expression of osteoblast marker genes Col I, Ocn and Bsp. Gene silencing of miR-9 in C2C12 resulted in the suppression of alkaline phosphatase activity and osteoblast mineralization, as well as the expression of Col I, Ocn and Bsp. DKK1 mRNA was not affected by miR-9 overexpression, however, DKK1 protein was significantly decreased. Moreover, DKK1 3'-UTR mediated transcriptional luciferase activity was also significantly suppressed by miR-9 overexpression. DKK1 mRNA was not affected by miR-9 gene silencing, however, DKK1 protein was significantly stimulated. Moreover, DKK1 3'-UTR mediated transcriptional luciferase activity was significantly stimulated by miR-9 gene silencing, and suppressed by miR-9 overexpression, however, DKK1 3'-UTR mutant mediated luciferase activity was unaffected. The siRNA derived gene silencing of DKK1 blocked the inhibiting effect of shmiR-9 on the expression of alkaline phosphatase; and blocked the inhibiting effect of shmiR-9 on the expression of ColI, Ocn and Bsp. MiR-9 promotes osteoblast differentiation of mesenchymal cell C2C12 by suppressing the gene expression of DKK1. PMID- 27393150 TI - Mathematical modelling of the growth of human fetus anatomical structures. AB - The goal of this study was to present a procedure that would enable mathematical analysis of the increase of linear sizes of human anatomical structures, estimate mathematical model parameters and evaluate their adequacy. Section material consisted of 67 foetuses-rectus abdominis muscle and 75 foetuses- biceps femoris muscle. The following methods were incorporated to the study: preparation and anthropologic methods, image digital acquisition, Image J computer system measurements and statistical analysis method. We used an anthropologic method based on age determination with the use of crown-rump length-CRL (V-TUB) by Scammon and Calkins. The choice of mathematical function should be based on a real course of the curve presenting growth of anatomical structure linear size Upsilon in subsequent weeks t of pregnancy. Size changes can be described with a segmental-linear model or one-function model with accuracy adequate enough for clinical purposes. The interdependence of size-age is described with many functions. However, the following functions are most often considered: linear, polynomial, spline, logarithmic, power, exponential, power-exponential, log logistic I and II, Gompertz's I and II and von Bertalanffy's function. With the use of the procedures described above, mathematical models parameters were assessed for V-PL (the total length of body) and CRL body length increases, rectus abdominis total length h, its segments hI, hII, hIII, hIV, as well as biceps femoris length and width of long head (LHL and LHW) and of short head (SHL and SHW). The best adjustments to measurement results were observed in the exponential and Gompertz's models. PMID- 27393151 TI - [Not Available]. AB - AIM: To describe the serious adverse drug reactions (ADR) in elderly subjects aged over 65 years and assess their preventability. METHODS: A retrospective study was conducted at the Regional Pharmacovigilance Center of Champagne-Ardenne (northeast of France) between January and May 2013. Patients aged over 65 years who presented a serious ADR notified to the Regional Pharmacovigilance Center were included in the study. RESULTS: Over the study period, 100 subjects were included in the study. The sex ratio was 0.96. Twenty seven percent of serious ADR were preventable. Off-label use accounted for 20% and non-compliance for 5%. Bleeding events were the most common serious ADR (36%). The drugs most frequently involved in serious ADR were antithrombotic agents (31.4%). CONCLUSION: More than a quarter of serious ADR were preventable. Off-label use and non-compliance are the main causes identified in the occurrence of preventable serious ADR. PMID- 27393152 TI - Challenges managing end-stage renal disease and kidney transplantation in a child with MTFMT mutation and moyamoya disease. AB - Moyamoya disease is a chronic cerebrovascular disorder with progressive stenosis. We describe a four-yr-old female with features of moyamoya disease referred to our center for kidney transplant evaluation with ESRD secondary to presumed renal dysplasia along with concern for cerebral vascular anomalies. With her constellation of organ involvement, a genetic workup revealed a homozygous, frameshift mutation in the mitochondrial methionyl-tRNA formyltransferase gene. Given her vascular anomalies and evidence of prior infarcts seen on cerebral imaging, it was felt that her risk of future stroke events was high and that hypotension or intravascular volume depletion would further exacerbate this risk. In hopes of improving her tenuous cerebral perfusion, she underwent a bilateral temporal craniotomy for superficial temporal artery to middle cerebral artery bypass. We highlight the challenges faced in a child with ESRD and kidney transplantation when cerebral vasculature is compromised. A multidisciplinary approach is critical in determining the need for a revascularization procedure prior to transplant and to help reduce the risk of ischemic or hemorrhagic events in this patient population. PMID- 27393153 TI - Pre- and Postoperative Predictors of Infection-Related Complications in Patients Undergoing Percutaneous Nephrolithotomy. AB - INTRODUCTION: We aim to describe pre- and postoperative predictors of infection related complications in individuals undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Patients treated with PCNL from 2009 to 2013 were reviewed. Patients with positive urine or stone cultures received extended antimicrobial treatment. All others received 7 days of empirical therapy preoperatively and postoperatively. Pre- and postoperative predictors of infectious complication were identified. RESULTS: We identified 227 patients who underwent primary PCNL with infectious complications occurring in 37 (16%): 11 (5%) urinary tract infection/pyelonephritis, 21 (9%) systemic inflammatory response syndrome (SIRS), and 2 (0.9%) sepsis. There were no significant differences between those with and without infectious complication with regard to age, gender, stone size, presence of diabetes, or procedure duration. Those with infectious complication were more likely to have a positive intraoperative stone culture (p = 0.01), struvite stone composition (p < 0.01), staghorn calculi (p < 0.001), and multiple stones (p = 0.02). Preoperatively, on multivariable analysis, only the presence of a staghorn calculus remained independently associated with increased risks of fever/SIRS/sepsis (odds ratio [OR] 3.14; p = 0.02) and total infectious complications (OR 2.53; p = 0.02) following PCNL. After controlling for pre- and post-PCNL risk factors, again, only staghorn calculi remained significantly associated with fever/SIRS/sepsis (OR 3.41; p = 0.01) and total infectious complications (OR 2.91; p = 0.01), with presence of multiple stones approaching significance (OR 4.2, confidence interval [CI]: 0.96, 18.6; p = 0.06). CONCLUSIONS: In individuals undergoing PCNL on preoperative antibiotics, risk of SIRS/sepsis was low. The presence of a staghorn calculus confers a greater than threefold increased risk of postoperative infection with multiple stones approaching a significant risk. Patients with large stone burdens should be counseled appropriately regarding these risks. PMID- 27393155 TI - Elastic properties of woven bone: effect of mineral content and collagen fibrils orientation. AB - Woven bone is a type of tissue that forms mainly during fracture healing or fetal bone development. Its microstructure can be modeled as a composite with a matrix of mineral (hydroxyapatite) and inclusions of collagen fibrils with a more or less random orientation. In the present study, its elastic properties were estimated as a function of composition (degree of mineralization) and fibril orientation. A self-consistent homogenization scheme considering randomness of inclusions' orientation was used for this purpose. Lacuno-canalicular porosity in the form of periodically distributed void inclusions was also considered. Assuming collagen fibrils to be uniformly oriented in all directions led to an isotropic tissue with a Young's modulus [Formula: see text] GPa, which is of the same order of magnitude as that of woven bone in fracture calluses. By contrast, assuming fibrils to have a preferential orientation resulted in a Young's modulus in the preferential direction of 9-16 GPa depending on the mineral content of the tissue. These results are consistent with experimental evidence for woven bone in foetuses, where collagen fibrils are aligned to a certain extent. PMID- 27393154 TI - mTORC2 Signaling Regulates Nox4-Induced Podocyte Depletion in Diabetes. AB - AIM: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mammalian target of rapamycin complex 2 (mTORC2) mediates podocyte injury in diabetes. RESULTS: High glucose (HG)-induced podocyte injury reflected by alterations in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway. HG also increased the levels of Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using small interfering RNA (siRNA)-targeting Rictor in vitro decreased HG-induced Nox1 and Nox4, NADPH oxidase activity, restored podocin levels, and reduced podocyte depletion/apoptosis. Inhibition of mTORC2 had no effect on mammalian target of rapamycin complex 1 (mTORC1) activation, described by our group to be increased in diabetes, suggesting that the mTORC2 activation by HG could mediate podocyte injury independently of mTORC1. In isolated glomeruli of OVE26 mice, there was a similar activation of the Rictor/mTORC2/Akt signaling pathway with increase in Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using antisense oligonucleotides targeting Rictor restored podocin levels, reduced podocyte depletion/apoptosis, and attenuated glomerular injury and albuminuria. INNOVATION: Our data provide evidence for a novel function of mTORC2 in NADPH oxidase-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. CONCLUSION: mTORC2 and/or NADPH oxidase inhibition may represent a therapeutic modality for diabetic kidney disease. Antioxid. Redox Signal. 25, 703-719. PMID- 27393156 TI - Simple and multiple linear regression: sample size considerations. AB - OBJECTIVE: The suggested "two subjects per variable" (2SPV) rule of thumb in the Austin and Steyerberg article is a chance to bring out some long-established and quite intuitive sample size considerations for both simple and multiple linear regression. STUDY DESIGN AND SETTING: This article distinguishes two of the major uses of regression models that imply very different sample size considerations, neither served well by the 2SPV rule. The first is etiological research, which contrasts mean Y levels at differing "exposure" (X) values and thus tends to focus on a single regression coefficient, possibly adjusted for confounders. The second research genre guides clinical practice. It addresses Y levels for individuals with different covariate patterns or "profiles." It focuses on the profile-specific (mean) Y levels themselves, estimating them via linear compounds of regression coefficients and covariates. RESULTS AND CONCLUSION: By drawing on long-established closed-form variance formulae that lie beneath the standard errors in multiple regression, and by rearranging them for heuristic purposes, one arrives at quite intuitive sample size considerations for both research genres. PMID- 27393157 TI - Protein phosphatase 2A inhibition and subsequent cytoskeleton reorganization contributes to cell migration caused by microcystin-LR in human laryngeal epithelial cells (Hep-2). AB - The major toxic mechanism of Microcystin-LR is inhibition of the activity of protein phosphatase 2A (PP2A), resulting in a series of cytotoxic effects. Our previous studies have demonstrated that microcystin-LR (MCLR) induced very different molecular effects in normal cells and the tumor cell line SMMC7721. To further explore the MCLR toxicity mechanism in tumor cells, human laryngeal epithelial cells (Hep-2) was examined in this study. Western blot, immunofluorescence, immunoprecipitation, and transwell migration assay were used to detect the effects of MCLR on PP2A activity, PP2A substrates, cytoskeleton, and cell migration. The results showed that the protein level of PP2A subunits and the posttranslational modification of the catalytic subunit were altered and that the binding of the AC core enzyme as well as the binding of PP2A/C and alpha4, was also affected. As PP2A substrates, the phosphorylation of MAPK pathway members, p38, ERK1/2, and the cytoskeleton-associated proteins, Hsp27, VASP, Tau, and Ezrin were increased. Furthermore, MCLR induced reorganization of the cytoskeleton and promoted cell migration. Taken together, direct covalent binding to PP2A/C, alteration of the protein levels and posttranslational modification, as well as the binding of subunits, are the main pattern for the effects of MCLR on PP2A in Hep-2. A dose-dependent change in p-Tau and p-Ezrin due to PP2A inhibition may contribute to the changes in the cytoskeleton and be related to the cell migration in Hep-2. Our data provide a comprehensive exposition of the MCLR mechanism on tumor cells. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 890-903, 2017. PMID- 27393158 TI - Anticholinergic properties of medications. PMID- 27393159 TI - Methods for Estimating the Parameters of Nonlinear Adsorption Isotherms of Langmuir and Freundlich Types from a Response Curve of Pulse Input of an Adsorbate. AB - Methods for estimating the parameters of nonlinear adsorption isotherms of Langmuir and Freundlich types from a pulse response curve are proposed here based on the migration rate of an adsorbate at a constant concentration and the mean residence time of the adsorbate in a bed. The methods were used to estimate the parameters in isotherms for various combinations of adsorbent and adsorbate. The isotherms estimated by the proposed methods were compared with those estimated by conventional methods. It was demonstrated that the proposed methods could evaluate the parameters with fairly good precision when the type of isotherm was known. The criteria for discriminating the type of isotherm from the pulse response curve are also described. PMID- 27393160 TI - Antioxidant Activity of Quercetin against Metmyoglobin-induced Oxidation of Fish Oil-bile Salt Emulsion. AB - The antioxidative effect of quercetin was examined in metmyoglobin-induced oxidation of a fish oil-bile salt emulsion (average diameter of particles; 2.0 MUm) to evaluate its effectiveness during the digestion of highly oxidizabile oils. The activity of quercetin increased with the lowering of the initial peroxide value (PV) of the oil and its effectiveness was superior to that of alpha-tocopherol. A synergistic antioxidant effect was observed upon the addition of quercetin and alpha-tocopherol irrespective of the initial PV of the oils, and quercetin was consumed faster than alpha-tocopherol. The loss of quercetin was larger than that of alpha-tocopherol when cumene hydroperoxide and metmyoglobin were mixed in a trimyristin-bile salt emulsion. In an ultrafiltration experiment on emulsified oil with a membrane filter of 100 nm pore size, the recovery of quercetin in the filtrate was higher than that of alpha-tocopherol. These data suggest that quercetin was an antioxidant in the digestion of fish oil. The effectiveness seems to come from its distribution in the emulsified oil, different from that of alpha-tocopherol, and its ability to scavenge radicals generated from the reaction of lipid hydroperoxides with metmyoglobin. PMID- 27393161 TI - Synthesis of Novel 25-Substituted Milbemycin A4 Derivatives and Their Acaricidal Activity against Tetranychus urticae. AB - Novel 25-substituted milbemycin A4 derivatives were synthesized from 25a hydroxymilbemycin A4 and 25b-hydroxymilbemycin A4, which had been obtained by the microbial oxidation of milbemycin A4. The acaricidal activity of each synthesized derivative was tested against Tetranychus urticae, and all of the synthesized derivatives showed higher activity than parent milbemycin A4. Some of the derivatives had higher acaricidal activity than milbemycin D, which had higher acaricidal activity than milbemycin A4. Among them, 25b-methylmilbemycin A4 was the most active derivative, with 100% mortality of the mite at a concentration of 1 ppm, and 63% mortality at 0.1 ppm. PMID- 27393162 TI - Analysis of Aggregate Structure in Food Protein Gels with the Concept of Fractal. AB - The fractal structure of the aggregates in food protein gels was analyzed. Three kinds of food protein gels were prepared: (1) beta-lactoglobulin (beta-LG) gel; (2) 11S soybean globulin gel; and (3) caseinate gel. From the concentration dependence of the gel elasticity, the fractal dimensions Df of the aggregates in the gels were evaluated, according to the theory of Shih et al. These gels showed the weak-link behavior described in the theory of Shih et al The values obtained for Df were 2.6-2.7, which were larger than those predicted by the cluster cluster aggregation model for a dilute system. In addition, for the beta-LG gels, the fractal dimension was also evaluated from the analysis of the gel image obtained with a confocal scanning laser microscopy, the value being close to that evaluated from the concentration dependence of the gel elasticity. These results indicate that the elastic behavior of the aggregate gels is a reflection of fractal structure of the aggregates in the gels. PMID- 27393163 TI - Measurement of Phenolic Compounds and Their Effect on Shikonin Production in Lithospermum Cultured Cells. AB - Shikonin production by Lithospevmum cell cultures is induced by transferring the cells into production medium. Six phenolic compounds, p-hydroxybenzoic acid, caffeic acid, sinapic acid, ferulic acid, syringaldehyde, and salicyclic acid, were detected in both shikonin-producing and non-producing cells. Their contents in the former were much lower than those in the latter except for salicylic acid, the content of which strongly increased when cells were producing shikonin. The cell wall fraction, after alkaline hydrolysis, gave two phenolic compounds, p hydroxybenzoic acid and caffeic acid. Their contents were much higher in shikonin producing cells than in shikonin-free cells. Of these compounds, exogenous addition of p-hydroxybenzoic acid increased shikonin production in the production medium. Although it is a precursor of shikonin, the increment of shikonin produced was much larger than the administered p-hydroxybenzoic acid, suggesting this compound has a stimulatory effect on shikonin biosynthesis at a low concentration. PMID- 27393164 TI - Efficient Production of gamma-Polyglutamic Acid by Bacillus subtilis (natto) in Jar Fermenters. AB - The large scale fermentation of gamma-polyglutamic acid (gamma-PGA) by Bacillus subtilis (natto) was done using a 30-liter jar fermenter. A stable cultivation without foaming could be done with addition of 3% NaCl to the medium. The gamma PGA productivity became higher with increasing speed of agitation and amounts of glutamic acid added to the broth. Finally, we were able to obtain about 35 mg/ml of gamma-PGA under the optimum conditions. The glutamic acid added to the medium was efficiently converted into gamma-PGA in the stationary phase. To discover the role of l-glutamic acid added to the medium for gamma-PGA biosynthesis by Bacillus subtilis (natto), the radioactivity incorporated into gamma-PGA from (14)C-l-glutamic acid was measured. As a result, radioactive gamma-PGA was detected in the medium. Then, the glutamic acid in the medium was transported into the cells and actually polymerized as the glutamic acid unit of gamma-PGA. PMID- 27393165 TI - Role of Divalent Metal Ions on Activity and Stability of Thermostable Dipeptidase from Bacillus stearothermophilus. AB - Thermostable dipeptidase from Bacillus stearothermophilus, a typical metalloenzyme containing 1.0g atom of Zn per mole of subunit of the dimeric enzyme was markedly activated by exogenous divalent metal ions such as Mn(2+), Co(2+), and Cd(2+) . In contrast, several others including Ba(2+), Hg(2+), and Cu(2+) considerably inhibited the enzyme, even the inherent metal, Zn(2+), being slightly inhibitory. To study the metal-binding properties of this dipeptidase, the enzyme was completely resolved to the inactive, Zn-free apoenzyme by treatment with EDTA in the presence of guanidine hydrochloride in a weakly acidic buffer. The apoenzyme was readily reconstituted by incubation with either Zn(2+), Mn(2+), or Co(2+), restoring the catalytic activity. The Mn-reconstituted enzyme had nearly twice the activity of the original Zn-enzyme. Combined with kinetic analyses of reconstitution of the apoenzyme with metal ions, these results show that the enzyme has two non-identical metal-binding sites, each with a different property. Furthermore, substitution of Mn(2+) or Co(2+) for Zn(2+) considerably lowered the thermostability of the enzyme without affecting the overall conformation of the enzyme protein, suggesting that the prosthetic Zn is playing dual roles in conformational stability and catalysis of the thermostable dipeptidase. PMID- 27393166 TI - Formation Mechanism of Monodehydro-l-ascorbic Acid and Superoxide Anion in the Autoxidation of l-Ascorbic Acid. AB - The oxidation of l-ascorbic acid (ASA) by molecular oxygen was studied in the absence of heavy metal ion catalysts. The formation of superoxide anion was confirmed during the autoxidation of ASA not only in aqueous solution but also in MeOH. The formation mechanism of superoxide anion was discussed based on both experimental and molecular orbital (MO) calculation results. It was proposed that ASA autoxidation proceeded via the C(2) oxygen adduct of ASA, and superoxide anion would be directly released from the C(2) oxygen adduct of ASA, forming monodehydro-ASA (MDASA). PMID- 27393167 TI - Synthesis of (R, Z)-7, 15-Hexadecadien-4-olide, the Sex Pheromone of the Yellowish Elongate Chafer (Heptophylla picea). AB - (R, Z)-7,15-Hexadecadien-4-olide, the sex pheromone of the yellowish elongate chafer (Heptophylla picea), was synthesized from l-malic acid in 15 steps. The synthetic pheromone was identical with the natural product in its MS, IR, GLC retention time, and biological activity. PMID- 27393168 TI - Purification of Levan Fructotransferase from Arthvobacter nicotinovoram GS-9 and Production of DFA IV from Levan by the Enzyme. AB - A bacterial strain, GS-9, isolated from soil as a levan-degrading microorganism produced an extracellular enzyme that converted levan into DFA IV. This strain was identified as Arthrobacter nicotinovorvans. The DFA IV-producing enzyme was specifically induced by levan. The enzyme was purified 60-fold from culture supernatant to give a single band on SDS-PAGE. The molecular weight of this enzyme was 52,000 by SDS-PAGE and a monomer by gel filtration. The enzyme gave DFA IV as a main product (> 75%), and fructose, levanbiose, and two unidentified oligosaccharides as minor products, and was identified as a novel levan fructotransferase. PMID- 27393169 TI - Efficient Syntheses of the OPC Homologous Series, OPC-1:0, -3:0, -4:0, -5:0, 6:0, -7:0, and-8:0. AB - The OPC homologous series was synthesized from 2-[(Z)-2-pentenyl]cyclopenten-1 one in short steps and with high yields. The carbon-carbon bond formation was achieved by the 1,4-conjugate addition approach. This method makes it possible to supply a sufficient amount of OPC homologues which would enable significant information to be collected for plant physiological studies. PMID- 27393170 TI - Identification of Methyl beta-Glucopyranoside and Xylose as Soluble Sugar Constituents in Roses (Rosa hybrida L.). AB - Two unidentified sugars were isolated from rose petals using HPLC. The isolated compounds were identified as methyl beta-glucopyranoside and xylose using (1)H NMR, (13)C-NMR, and GC-MS. Methyl beta-glucopyranoside and xylose were distributed in three cultivars tested relatively in large amounts. These results indicate that methyl beta-glucopyranoside and xylose occur universally as soluble sugar constituents in roses. PMID- 27393171 TI - Anthraquinone Production by Cell Suspension Cultures of Rubia akane Nakai. AB - The effects of various plant growth regulators and nutrients on cell growth and anthraquinone production in cell suspension cultures of Rubia akane Nakai were investigated. Use of an optimized medium resulted in a two-fold increase in the anthraquinone content. From the cell cultures 1,2-dihydroxyanthraquinone was isolated as the main constituent. PMID- 27393172 TI - Semi Quantification of Gibberellins in the Anthers of Thermosensitive Genetic Male Sterile Rice (Oryza sativa L. cv. PL12). AB - The levels of endogenous GAs in the anthers of rice (Oryza sativa L., cv. Reimei (normal)) and in those of sterile and fertile plants of a thermosensitive genetic male sterile line (Norin PL12; derived from Reimei) were measured by enzyme linked immunosorbent assay (ELISA). High levels of GA4/7 were detected in the anthers of Reimei (normal fertility) and fertile (growing under fertile conditions) PL 12, while such levels were markedly reduced with increased sterility in PL12. The anthers of the plants exposed to the sterile conditions contained undeveloped pollens. These results suggest that the occurrence of GA4/7 was closely related to the expression of the sterility gene and the growth and/or development of the anther and/or pollen PL12. PMID- 27393173 TI - A Sensitive and Rapid Method for Mapping Protein Bound to DNA by Atomic Force Microscopy. AB - We addressed the strategies of mapping protein binding sites on a DNA fragment by atomic force microscopy (AFM). The protein binding site was uniquely mapped by distinguishing two termini of a linear DNA fragment. Our simple methods were found very useful to get information on transcription regulatory regions by taking advantage of long range and quick scanning by AFM. PMID- 27393174 TI - Purification and Some Properties of an alpha-Amylase from an Anaerobic Bacterium Isolated from Coastal Sediment. AB - A marine, obligate anaerobic bacterium, SS71, isolated from a coastal sediment, was a Gram-positive, asporogenous, rod-shaped organism with a G + C mol% of 37.3 +/-0.1. This bacterium produced an alpha-amylase with a molecular mass of 91 kDa and an isoelectric point of 4.3. The alpha-amylase had an optimal pH of 7.0 and an optimal temperature of 35 degrees C. The enzyme activity was promoted by 0.5 2.0% NaCl. PMID- 27393175 TI - Gibberellin Metabolism in Intact Plants of Raphanus sativus L. AB - The metabolism of gibberelline (GAs) in intact plants of Raphanus sativus was investigated. With [(2)H]GA feeds, [(2)H]GA1 from [(2)H]GA4, and [(2)H]GA4 and [(2)H]GA20 from [(2)H]GA9 were metabolized. Since [(2)H]GA20 was not converted into [(2)H]GA1, endogenous GA1 may have been biosynthesized from GA9 via GA4 rather than from GA20. The radioactivity of [(3)H]GA9 and [(3)H]GA20 was much more strongly transported among the plant organs than that of [(3)H]GA1 and [(3)H]GA4. PMID- 27393176 TI - Cytochrome b/f Complex Is Not Involved in Respiration in the Cyanobacterium Synechocystis PCC 6803 Grown Photoautotrophycally. AB - Respiratory oxygen uptake was not suppressed by the inhibitor of the quinol oxidation site of cytochrome b/f complex 2,5-di-bromo-3-methyl-6-isopropyl-p benzoquinone (DBMIB), but by far-red illumination in Synechocystis PCC 6803 cells grown photoautotrophically. It is proposed that cytochrome b/f complex is not involved in the respiratory electron transport. PMID- 27393177 TI - Antioxidative Activity of Water Extracts of Lagerstroemia speciosa Leaves. AB - In order to develop naturally occurring antioxidants from edible plants, the antioxidative effect of hot water extracts of Lagerstroemia speciosa leaves, known by the Tagalog name of banaba in the Phillipines, was studied. The content of tannin in banaba extract was 36.8% in dry weight. Banaba extract showed strong antioxidative activity in a linoleic acid autoxidation system. Banaba extract was found to have a potent radical scavenging action on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and superoxide radicals (O(2-) ) generated by a hypoxanthine (HPX)/xanthine oxidase (XOD) system. In vitro lipid peroxidation of rat liver homogenate induced by tert-butyl hydroperoxide (BHP) was inhibited by the addition of banaba extract in a dose-dependent manner. From these results, banaba extract was demonstrated to be useful as an antioxidant or free radical scavenger to protect biological systems against oxidative stress. PMID- 27393178 TI - A Novel Type of D-Mannitol Dehydrogenase from Acetobacter xylinum: Occurrence, Purification, and Basic Properties. AB - We purified a novel type of D-mannitol dehydrogenase, which contains a c-type cytochrome and an unknown chromophore in the soluble fraction of an acetic acid bacterium, Acetobacter xylinum KU-1, to homogeneity. The enzyme showed the maximum activity at pH 5 and 40 degrees C. It was stable up to 60 degrees C at pH 6, and was inhibited by Hg(2+) and p-quinone (Ki = 0.18 mm). The molecular weight of the enzyme was about 140,000, and those of the subunits were 69,000, 51,000, and 20,000; the enzyme is hetero-trimeric and contained 8 g-atoms of Fe per mole. The alpha-helix content was estimated to be about 52.9%. The enzyme catalyzed phenazine methosulfate dependent oxidation of d-mannitol with an apparent Km of 98 MUm (for d-mannitol) and Vmax of 213 MUmol/min/mg. The reduced form of the enzyme showed the absorption maxima at 386, 416, 480, 518, 550, and 586 nm, which are attributable to a c-type cytochrome in the enzyme. PMID- 27393179 TI - Expanding the first link in the chain of survival - Experiences from dispatcher referral of callers to AED locations. AB - INTRODUCTION: Early use of automated external defibrillators (AED) increases survival in cases of out-of-hospital cardiac arrest (OHCA). Dispatchers play important roles in identifying OHCA, dispatching ambulances and providing callers with telephone-assisted cardiopulmonary resuscitation. Guidelines recommend that AED registries be linked to dispatch centres as tools to refer callers to nearby AED. AIM: The aim of this study was to investigate to what extent dispatchers, when provided with a tool to display AED locations and accessibility, referred callers to nearby AED. METHODS: An application providing real-time visualization of AED locations and accessibility was implemented at four dispatch centres in Sweden. Dispatchers were instructed to refer callers to nearby AED when OHCA was suspected. Such cases were prospectively collected, and geographic information systems were used to identify those located <=100m from an AED. Audio recordings of emergency calls were assessed to evaluate the AED referral rate. RESULTS: Between February and August 2014, 3009 suspected OHCA calls were received. In 6.6% of those calls (200/3009), an AED was <=100m from the suspected OHCA. The AED was accessible and the caller was not alone on scene in 24% (47/200) of these cases. In two of those 47 cases (4.3%), the dispatcher referred the caller to the AED. CONCLUSION: Despite a tool for dispatchers to refer callers to a nearby AED, referral was rare. Only a minority of the suspected OHCA cases occurred <=100m from an AED. We identified AED accessibility and callers being alone on scene as obstacles for AED referral. PMID- 27393181 TI - Underprotection of Unpredictable Statistical Lives Compared to Predictable Ones. AB - Existing ethical discussion considers the differences in care for identified versus statistical lives. However, there has been little attention to the different degrees of care that are taken for different kinds of statistical lives. Here we argue that for a given number of statistical lives at stake, there will sometimes be different, and usually greater, care taken to protect predictable statistical lives, in which the number of lives that will be lost can be predicted fairly accurately, than for unpredictable statistical lives, where the lives are at stake because of a low-probability event, such that most likely no one will be affected by the decision but with low probability some lives will be at stake. One reason for this difference is the statistical challenge of estimating low probabilities, and in particular the tendency of common approaches to underestimate these probabilities. Another is the existence of rational incentives to treat unpredictable risks as if the probabilities were lower than they are. Some of these factors apply outside the pure economic context, to institutions, individuals, and governments. We argue that there is no ethical reason to treat unpredictable statistical lives differently from predictable statistical lives. Moreover, lives that are unpredictable from the perspective of an individual agent may become predictable when aggregated to the level of a societal decision. Underprotection of unpredictable statistical lives is a form of market failure that may need to be corrected by altering regulation, introducing compulsory liability insurance, or other social policies. PMID- 27393180 TI - Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers. AB - PURPOSE: Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. METHODS: We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. RESULTS: We found significantly decreased levels of CTGF mRNA and protein (both p < 0.0000001) in cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. CONCLUSIONS: Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development. PMID- 27393182 TI - Subclinical cardiovascular disease and it's improvement after long-term TNF-alpha inhibitor therapy in severe psoriatic patients. AB - BACKGROUND: There are conflicting data on the occurrence of subclinical myocardial dysfunction in psoriatic patients and on the impact of long-term tumour necrosis factor-alpha (TNF-alpha) inhibitor therapy on cardiac function. OBJECTIVE: In this study, we explored whether there are any signs of subclinical cardiovascular disease (echocardiographic abnormalities) in severe psoriatic patients without clinically overt heart disease. As a second objective, the influence of long-term treatment with TNF-alpha inhibitors on the ventricular functions of psoriatic patients was also investigated. METHODS: Clinical and echocardiographic data from 44 psoriatic patients and 45 age- and sex-matched controls were processed. As a first step, the echocardiographic parameters of psoriatic patients obtained before anti-TNF-alpha treatment were compared with controls. As a second step, to detect the effect of long-term anti-TNF-alpha treatment on echocardiographic parameters, data of patients before and after therapy were analysed. RESULTS: The right ventricular Tei index was higher (P < 0.001), whereas the tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall peak systolic velocity were lower (P < 0.001 and P < 0.0001, respectively) in the psoriatic patients than in the controls. Following treatment with TNF-alpha inhibitors, TAPSE and right ventricular free wall peak systolic velocity significantly improved (P < 0.0001 for both parameters). The Tei index of both ventricles improved during biological therapy; however, this change did not reach statistical significance. CONCLUSION: Patients with severe psoriasis exhibit signs of subclinical cardiovascular disease compared to control, and prolonged anti-TNF-alpha therapy has a potentially beneficial effect on these signs. PMID- 27393183 TI - Patient satisfaction with nipple-sparing mastectomy: A prospective study of patient reported outcomes using the BREAST-Q. AB - BACKGROUND AND OBJECTIVES: The authors sought to study patient-reported outcomes following nipple-sparing mastectomy (NSM). METHODS: From 2008 to 2011, the BREAST Q was administered to women undergoing NSM surgery for cancer treatment or risk reduction prior to surgery and at 2 years after completion of reconstruction. The change in score over time and the impact of surgical indication, complication occurrence, and laterality on scores were analyzed. RESULTS: The BREAST-Q was prospectively administered to 39 women undergoing NSM for cancer treatment (n = 17) or risk-reduction (RR) (n = 22). At 2 years after operation, median overall satisfaction with breasts was 75 (IQR = 67,100). There were significant postoperative increases in scores for overall satisfaction with breasts (+8, P = 0.021) and psychosocial well-being (+14, P = 0.003). Postoperatively, RR patients had significantly higher scores for psychosocial wellness, physical impact (chest), and overall satisfaction with outcome compared to cancer treatment patients (P < 0.05). Also, increase from preoperative to postoperative psychosocial wellness was higher in the RR compared to cancer treatment patients (+17 vs. +1, P = 0.043). Complication occurrence did not significantly impact postoperative scores. CONCLUSIONS: Following NSM for cancer treatment or RR, patients demonstrated high levels of satisfaction and quality of life as measured by BREAST-Q. Satisfaction level increased 2 years following operation. J. Surg. Oncol. 2016;114:416-422. (c) 2016 Wiley Periodicals, Inc. PMID- 27393184 TI - [Not Available]. AB - BACKGROUND: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. RESULTS: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. CONCLUSION: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population. PMID- 27393185 TI - [Not Available]. AB - OBJECTIVE: The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population. METHOD: We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1year. Each patient had a dosage of azathioprine metabolites. RESULTS: We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients. CONCLUSION: Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule. PMID- 27393187 TI - Anticoagulants: Major Advances Without Clear Consensus. AB - Therapeutics for thrombosis were discovered because of observations made nearly one hundred years ago. The mainstays of these treatments have been either heparin or warfarin, with the latter being preferred for long-term anticoagulation. In the last six years, newer agents with antigoagulant activities have been approved for clinical use. These agents have advantages and disadvantages over warfarin and consensus for their use is still being formed, as is the manner in which the more traditional agents, such as warfarin, should be used and monitored. PMID- 27393190 TI - Neurosurgical Treatment Variation of Traumatic Brain Injury: Evaluation of Acute Subdural Hematoma Management in Belgium and The Netherlands. AB - Several recent global traumatic brain injury (TBI) initiatives rely on practice variation in diagnostic and treatment methods to answer effectiveness questions. One of these scientific dilemmas, the surgical management of the traumatic acute subdural hematoma (ASDH) might be variable among countries, among centers within countries, and even among neurosurgeons within a center, and hence be amenable for a comparative effectiveness study. The aim of our questionnaire, therefore, was to explore variations in treatment for ASDH among neurosurgeons in similar centers in a densely populated geographical area. An online questionnaire, involving treatment decisions on six case vignettes of ASDH, was sent to 93 neurosurgeons in The Netherlands and Belgium. Clinical and radiological variables differed per case. Sixty neurosurgeons filled out the questionnaire (response rate 65%). For case vignettes with severe TBI and an ASDH, there was a modest variation in the decision to evacuate the hematoma and a large variation in the decision to combine the evacuation with a decompressive craniectomy. The main reasons for operating were "neurological condition" and "mass effect." For ASDH and mild/moderate TBI, there was large variation in the decision of whether to operate or not, whereas "hematoma size" was the predominant motivation for surgery. Significant inter-center variation for the decision to evacuate the hematoma was observed (p = 0.01). Most pronounced was that 1 out of 7 (14%) neurosurgeons in one region chose a surgical strategy compared with 9 out of 10 (90%) in another region for the same scenario. In conclusion, variation exists in the neurosurgical management of TBI within an otherwise homogeneous setting. This variation supports the methodology of the international Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) initiative, and shaped the Dutch Neurotraumatology Quality Registry (Net-QuRe) initiative. PMID- 27393191 TI - The role of ICP monitoring in patients with persistent cerebrospinal fluid leak following spinal surgery: a case series. AB - BACKGROUND: Cerebrospinal fluid (CSF) leak following spinal surgery is a relatively common surgical complication. A disturbance in the underlying CSF dynamics could be the causative factor in a small group of patients with refractory CSF leaks that require multiple surgical repairs and prolonged hospital admission. METHODS: A retrospective case series of patients with persistent post spinal surgery CSF leak referred to the hydrocephalus service for continuous intracranial pressure (ICP) monitoring. Patients' notes were reviewed for medical history, ICP data, radiological data, and subsequent management and outcome. RESULTS: Five patients (two males/three females, mean age, 35.4 years) were referred for ICP monitoring over a 12-month period. These patients had prolonged CSF leak despite multiple repair attempts 252 +/- 454 days (mean +/- SD). On ICP monitoring, all five patients had abnormal results, with the mean ICP 8.95 +/- 4.41 mmHg. Four had abnormal pulse amplitudes, mean 6.15 mmHg +/- 1.22 mmHg. All five patients underwent an intervention. Three patients underwent insertion of ventriculoperitoneal (VP) shunts. One patient had venous sinus stent insertion and one patient underwent medical management with acetazolamide. All five of the patients' CSF leak resolved post intervention. The mean time to resolution of CSF leak post intervention was 10.8 +/- 12.9 days. CONCLUSIONS: Abnormal cerebrospinal fluid dynamics could be the underlying factor in patients with a persistent and treatment-refractory CSF leak post spinal surgery. Treatments aimed at lowering ICP may be beneficial in this group of patients. Whether abnormal pressure and dynamics represent a pre-existing abnormality or is induced by spinal surgery should be a subject of further study. PMID- 27393192 TI - Cost-effectiveness of phosphate binders among patients with chronic kidney disease not yet on dialysis: a long way to go. AB - Hyperphosphatemia management is integral to the management of patients with chronic kidney disease. This mineral abnormality is associated with greater costs, but so is its management, especially with the use novel phosphate binders. The economic evaluation of these pharmaceutical agents is increasingly needed to provide evidence for value of money spent and inform resource allocation. Recently, Nguyen et al. explored the economical attractiveness of Sevelamer relative to Calcium Carbonate among patients with chronic kidney disease not yet on dialysis and concluded that the former was cost-effective. The current commentary discusses the results of this analysis and sheds light on the methodological challenges of economic evaluations in this field. PMID- 27393193 TI - Phosphorus source-sink relationships of stream sediments in the Rathbun Lake watershed in southern Iowa, USA. AB - The surface waters of Rathbun Lake watershed in southern Iowa are impacted by agricultural sources of sediments and nutrients, including phosphorus (P). Because stream sediments often play an important role in regulating P concentrations in stream water, we investigated sediment-water column P relationships in four creeks within the watershed and then evaluated the relationship between sediment properties and indicators of the risk of P loss. Based on Mehlich-3-extractable P (17 to 68 mg kg(-1)) and degree of P saturation (2 to 12 %), stream bank and bed sediments at the four sites were unlikely to serve as major sources of P. However, equilibrium P concentrations, which ranged from 0.02 to 0.12 mg L(-1), indicated that bed sediments could release P to the water column depending on dissolved P (DP) concentrations in the stream water and the time of year. The likelihood of P desorption from the sediments increased with increasing pH (r = 0.92, p < 0.01) and sand content (r = 0.78, p < 0.05), but decreased with clay content (r = -0.72, p < 0.05) and iron (Fe) (r = -0.93, p < 0.001) associated with organic matter. From these results, we speculate that changes in land use within the riparian areas may, at least initially, have little effect on P concentrations in the streams. Low concentrations of DP relative to total P (TP) in these streams, however, suggest that P loads to Rathbun Lake can be reduced if P inputs from eroded bank sediments are controlled. PMID- 27393194 TI - Long-term decreases in phosphorus and suspended solids, but not nitrogen, in six upper Mississippi River tributaries, 1991-2014. AB - Long-term trends in tributaries provide valuable information about temporal changes in inputs of nutrients and sediments to large rivers. Data collected from 1991 to 2014 were used to investigate trends in total nitrogen (TN), total phosphorus (TP), nitrate (NO3-N), soluble-reactive P (SRP), and total suspended solids (TSS) in the following six tributaries of the upper Mississippi River: Cannon (CaR; Minnesota (MN)), Maquoketa (MR; Iowa (IA)), Wapsipinicon (WR; IA), Cuivre (CuR; Missouri (MO)), Chippewa (ChR; Wisconsin (WI)), and Black (BR; WI) rivers. Weighted regression on time discharge and season was used to statistically remove effects of random variation in discharge from estimated trends in flow-normalized concentrations and flux. Concentration and flux of TSS declined in all six rivers. Concentration of P declined in four of the rivers, and P flux declined in five rivers. Concentration and flux of N exhibited small changes relative to TP. TN concentration and flux did not change substantially in four of the rivers and decreased in two (ChR, CuR). Nitrate concentration and flux increased in three rivers (ChR, BR, CaR) and remained relatively constant in the other three rivers. General declines in P and TSS suggest that improvements in agricultural land management, such as the adoption of conservation tillage and enrollment of vulnerable acreage into the Conservation Reserve Program, may have reduced surface runoff; similar reductions in N were not observed. PMID- 27393195 TI - Pairing high-frequency data with a link-node model to manage dissolved oxygen impairment in a dredged estuary. AB - High-frequency data and a link-node model were used to investigate the relative importance of mass loads of oxygen-demanding substances and channel geometry on recurrent low dissolved oxygen (DO) in the San Joaquin River Estuary in California. The model was calibrated using 6 years of data. The calibrated model was then used to determine the significance of the following factors on low DO: excavation of the river to allow navigation of large vessels, non-point source pollution from the agricultural watershed, effluent from a wastewater treatment plant, and non-point source pollution from an urban area. An alternative metric for low DO, excess net oxygen demand (ENOD), was applied to better characterize DO impairment. Model results indicate that the dredged ship channel had the most significant effect on DO (62 % fewer predicted hourly DO violations), followed by mass load inputs from the watershed (52 % fewer predicted hourly DO violations). Model results suggest that elimination of any one factor will not completely resolve DO impairment and that continued use of supplemental aeration is warranted. Calculation of ENOD proved more informative than the sole use of DO. Application of the simple model allowed for interpretation of the extensive data collected. The current monitoring program could be enhanced by additional monitoring stations that would provide better volumetric estimates of low DO. PMID- 27393197 TI - [Not Available]. PMID- 27393198 TI - [Not Available]. AB - Nevirapine, a HIV non nucleosidic reverse transcriptase inhibitor, displays an inter-individual variability in its pharmacokinetics parameters, related to its hepatic metabolism. Based on literature, is the nevirapine therapeutic drug monitoring relevant? In naive and pre-treated HIV infected patients, the probability of achieving and maintaining an undetectable HIV viral load was significantly associated with a nevirapine plasma trough concentration (Ctrough) >4000 ng/mL. The probability of virologic failure was significantly associated with a Ctrough <3000 ng/mL. Concerning the exposure-toxicity relationship, the emergence of hepatotoxicity was more frequently associated with high Ctrough, especially in case of HCV coinfection. Non-randomized studies have reported the interest of nevirapine therapeutic drug monitoring to optimize the virologic response and, to a lesser extent, to prevent hepatotoxicity. Therefore, the level of evidence of the interest of nevirapine therapeutic drug monitoring is "recommended". PMID- 27393196 TI - Interspecific differences in foliar 1 PAHs load between Scots pine, birch, and wild rosemary from three polish peat bogs. AB - Pine needles are one of the most commonly used bioindicators of polycyclic aromatic hydrocarbons (PAHs) in the environment. Therefore, the main objective of the current research was the assessment of PAHs accumulation potential of Scots pine (Pinus sylvestris L.) needles in comparison to wild rosemary (Rhododendron tomentosum Harmaja) and birch (Betula spp.) leaves. Our study was carried out on three peat bogs subjected to different degree of anthropopression, which gave us also the opportunity to identify local emission sources. Pine needles had the lowest accumulation potential from all the studied species. The highest accumulation potential, and hence carcinogenic potential, was observed for wild rosemary leaves. As far as emission sources are concerned, the most pronounced influence on atmospheric PAHs loads had traditional charcoal production, resulting in great influx of heavy PAHs. Observed seasonal changes in PAHs concentrations followed the pattern of winter increase, caused mainly by heating season, and summer decrease, caused mainly by volatilization of light PAHs. PMID- 27393199 TI - [Not Available]. AB - The efavirenz, a non nucleoside reverse transcriptase inhibitor of HIV-1, presents a marked pharmacokinetics variability related to an intense hepatic metabolism. Efavirenz is also a potent inducer. Central nervous system (CNS) toxicity associated with efavirenz therapy is a major cause of non adherence and therefore treatment failure. The literature has been analyzed to evaluate the level of evidence of the interest of a therapeutic drug monitoring for efavirenz. Several studies have reported that an efavirenz plasma concentration > 1000 ng/mL is a predictive factor of the viral response. Efavirenz plasma concentrations > 4000 ng/mL were associated to an increase frequency of CNS side effects. CNS toxicity was also more frequent in patients carrying the 516G > T mutation (CYP2B6*6 allele), associated with a significantly greater efavirenz plasma exposure. Non-randomized studies have reported the interest of efavirenz therapeutic drug monitoring to optimize viral response and prevent CNS toxicity, allowing to suggest a level of evidence "recommended" for efavirenz. PMID- 27393200 TI - [Not Available]. AB - The human immunodeficiency virus (HIV) protease inhibitor saquinavir displays a large inter-individual variability in its pharmacokinetic parameters, related to a low absorption rate and an important hepatic metabolism. Based on literature, is the saquinavir therapeutic drug monitoring relevant? In naive HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a saquinavir plasma trough concentration > 100 ng/mL. Two studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of virologic response with a threshold value around 40 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 abdominal pains was more frequently associated with high concentrations of saquinavir, but without threshold value determination. Several studies, one of which was randomized, have reported the interest of saquinavir therapeutic drug monitoring to optimize the virologic response. Therefore, the level of evidence of the interest of saquinavir therapeutic drug monitoring is "recommended". PMID- 27393201 TI - [Not Available]. AB - The HIV protease inhibitor atazanavir presents a wide inter-individual variability related to an intense hepatic metabolism. Dose-dependant elevations of bilirubin have been frequently reported with atazanavir. Relative to literature, the atazanavir therapeutic drug monitoring can it be proposed? In naive HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a plasma trough concentration (Cmin) of atazanavir >200 ng/mL. Studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of the virologic response with a threshold value around 200 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 hyperbilirubinemia was more frequently associated with Cmin>750-800 ng/mL. Non randomized studies have reported the interest of atazanavir therapeutic drug monitoring to optimize the virologic response and prevent severe bilirubin elevations. Therefore, the level of evidence of the interest of atazanavir therapeutic drug monitoring is recommended. PMID- 27393202 TI - [Not Available]. AB - Ribavirin in combination with pegylated interferon alpha is the current treatment for chronic hepatitis C (HCV). Ribavirin presents a wide inter-individual pharmacokinetic variability and adequate exposure seems crucial for achieving sustained virologic response. Severe anaemia frequently occurred under ribavirin treatment and is a dose-dependent limiting side effect. Several studies have been carried out in HVC-infected or HIV-HCV co-infected patients to evaluate the pharmacokinetic-pharmacodynamic relationships of ribavirin. Achievement of a sustained virologic response, defined as undetectable HCV-RNA six months after the end of treatment, have been significantly associated with ribavirin concentration. A cut-off for the trough concentration of ribavirin ranging between 2-3MUg/ml at week 4 has been proposed. A significant correlation has also been reported between ribavirin concentration and the extent of haemoglobin decline. A ribavirin concentration>2MUg/ml is significantly associated to an increase risk of severe anaemia. Non randomized studies have shown that therapeutic drug monitoring of ribavirin improve the management of therapeutic response and haematologic toxicity. Therefore, the level of evidence of the therapeutic drug monitoring of ribavirin is recommended. PMID- 27393203 TI - [Not Available]. AB - The HIV protease inhibitor lopinavir presents a wide inter-individual variability related to liver and intestinal metabolism involving CYP3A. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of lopinavir could improve patient care. In naive or pretreated HIV infected patients, no relationship could be evidenced between virological efficacy and trough lopinavir concentration, most likely because concentrations are above inhibitory concentrations. Although data are limited, patients with elevated triglycerides and cholesterol had trough lopinavir concentrations >8000 ng/mL. These data suggest that the level of evidence of interest of lopinavir therapeutic drug monitoring is may be recommended in some situations such as children, pregnant women, pretreated patients if the number of mutations is <5, when coadministration with drug with metabolizing enzyme inducing properties is warranted and toxicity. PMID- 27393204 TI - [Not Available]. AB - The HIV protease inhibitor indinavir presents a wide inter-individual variability related to an intense hepatic metabolism. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of indinavir could improve patient care. It was reported that indinavir virological efficacy in HIV-infected patients with wild-type virus was significantly associated with trough concentrations >100-150ng/mL. Concerning the exposure-toxicity relationship, the risk of occurrence of nephrotoxicity was more frequently associated with trough concentrations >500-1 000ng/mL. Studies with concentration controlled indinavir therapy suggest that therapeutic drug monitoring allows to achieve safe and effective concentrations, therefore, the level of evidence of the interest of indinavir therapeutic drug monitoring is highly recommended when indinavir is not associated with ritonavir and recommended when ritonavir is combined with ritonavir. PMID- 27393205 TI - [Not Available]. AB - OBJECTIVE: We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria(r) and Panenza(r). METHODS: It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. RESULTS: The number of subjects vaccinated by Focetria(r) is more important than Panenza(r). The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria(r) adverse effects were more frequent than Panenza(r) ones (p=0.009). Almost all adverse events disappeared within few days. CONCLUSION: The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used. PMID- 27393206 TI - Independent catalysis of the short form HisG from Lactococcus lactis. AB - ATP-phosphoribosyltransferase (ATP-PRT) catalyses the first step of histidine biosynthesis. Two different forms of ATP-PRT have been described; the homo hexameric long form, and the hetero-octameric short form. Lactococcus lactis possesses the short form ATP-PRT comprising four subunits of HisGS , the catalytic subunit, and four subunits of HisZ, a histidyl-tRNA synthetase paralogue. Previous studies have suggested that HisGS requires HisZ for catalysis. Here, we reveal that the dimeric HisGS does display ATP-PRT activity in the absence of HisZ. This result reflects the evolutionary relationship between the long and short form ATP-PRT, which acquired allosteric inhibition and enhanced catalysis via two divergent strategies. PMID- 27393207 TI - Reply. PMID- 27393208 TI - Changes in work behavior during pregnancy in rural Anhui, China from 2001-03 to 2009: a population based cross-sectional study. AB - BACKGROUND: In low- and middle-income countries, many women continue working later into pregnancy. In our recent study on some areas in rural China, most women stopped working already during the first trimester (<=3 months) of pregnancy. In this paper we aimed to explore whether stopping work during early pregnancy has changed over an 8 year period (between 2001-03 and 2009); we also studied whether the reasons for stopping work early were the same in the two time periods. METHODS: A population-based cross-sectional survey with a representative sample of new mothers was carried out in one rural county in Anhui Province in 2001-03 (N = 1479 respondents) and in two other rural counties in 2009 (N = 1574 respondents). Both surveys were used to evaluate prenatal care interventions not related to work behavior. The surveys targeted all women who had recently given birth. Multilevel logistic regression analysis was used to examine the determinants of work behavior in the two time periods. RESULTS: There was a big change in the working behavior between the two survey years: in the period 2001 03 6 % and in 2009, 53 % of pregnant women stopped working at <=3 months (percentage change 839, 95 % CI -15.90 to 1694.49). In 2001-03, 30 % and in 2009, 23 % of pregnant women worked the same as before pregnancy (percentage change 22.30, 95 % CI -90.28 to 45.68). In both time periods women with two children were less likely to stop work at <=3 months of pregnancy. Non-farmers were more likely in 2001-03 but less likely in 2009 to stop work at <=3 months of pregnancy. Women with medium township-level income were more likely to maintain the same level of work as before pregnancy in 2001-03, while in 2009 women with high township-level income were less likely to work the same. CONCLUSION: Stopping work very early during pregnancy appeared to have become very common from 2001-3 to 2009 in rural Anhui, China and was not explained by women's background characteristics. PMID- 27393209 TI - Ethylene glycol toxicity : MRI brain findings. PMID- 27393210 TI - Long-term underwater sound measurements in the shipping noise indicator bands 63Hz and 125Hz from the port of Falmouth Bay, UK. AB - Chronic low-frequency anthropogenic sound, such as shipping noise, may be negatively affecting marine life. The EU's Marine Strategy Framework Directive (MSFD) includes a specific indicator focused on this noise. This indicator is the yearly average sound level in third-octave bands with centre frequencies at 63Hz and 125Hz. These levels are described for Falmouth Bay, UK, an active port at the entrance to the English Channel. Underwater sound was recorded for 30min h(-1) over the period June 2012 to November 2013 for a total of 435days. Mean third octave levels were louder in the 125-Hz band (annual mean level of 96.0dB re 1MUPa) than in the 63-Hz band (92.6dB re 1 MUPa). These levels and variations are assessed as a function of seasons, shipping activity and wave height, providing comparison points for future monitoring activities, including the MSFD and emerging international regulation. PMID- 27393211 TI - Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore. AB - This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to MUg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species. PMID- 27393212 TI - Marine protected area design patterns in the Mediterranean Sea: Implications for conservation. AB - Mediterranean marine protected area (MPA) design patterns regarding geographic distribution, size, spacing and shape were analysed as a proxy of the region's MPA's ecological effectiveness and a first step towards an ecologically coherent MPA network. Results for legally designated MPAs and ecologically functional MPAs accounting for overlaps are presented. Geographically, Mediterranean MPA area is very unevenly distributed, with four-fifths concentrated in just three countries of the north-western part of the basin. Average distance between functional MPAs lies within recommended ecological thresholds, which suggests adequate potential connectivity of the Mediterranean MPA system. Mediterranean designated MPAs are larger than MPAs worldwide on average, although they are generally smaller than international guidance suggests at different levels: ecoregion, country and designation category. On average, Mediterranean designated and functional MPAs have relatively high compactness, which makes them prone to spillover and adequate viability, and less vulnerable to edge effects. PMID- 27393213 TI - Offshore oil spill response practices and emerging challenges. AB - Offshore oil spills are of tremendous concern due to their potential impact on economic and ecological systems. A number of major oil spills triggered worldwide consciousness of oil spill preparedness and response. Challenges remain in diverse aspects such as oil spill monitoring, analysis, assessment, contingency planning, response, cleanup, and decision support. This article provides a comprehensive review of the current situations and impacts of offshore oil spills, as well as the policies and technologies in offshore oil spill response and countermeasures. Correspondingly, new strategies and a decision support framework are recommended for improving the capacities and effectiveness of oil spill response and countermeasures. In addition, the emerging challenges in cold and harsh environments are reviewed with recommendations due to increasing risk of oil spills in the northern regions from the expansion of the Arctic Passage. PMID- 27393214 TI - Public awareness and attitudes towards marine protection in the United Kingdom. AB - Public perception research evaluating awareness and attitudes towards marine protection is limited in the United Kingdom (UK) and worldwide. Given public opinion can help drive policy and affect its successful delivery we conducted nationwide surveys in 2005, 2010 and 2015 to assess public knowledge of UK (England, Scotland and Wales) sea 'health' and management. Respondents from all three surveys were relatively pessimistic about sea 'health', perceiving this as poor-fair and largely in decline. Enthusiasm for marine conservation was high with almost two-thirds of respondents in each survey wanting >40% of UK seas highly protected from fishing and damaging activities. In 2015 there was considerable dissatisfaction with the rate of progress in Marine Conservation Zone designation and over three-quarters of respondents considered dredging and trawling to be inappropriate in protected areas, contrary to management. The UK government and devolved administrations need to better align future conservation and management with public expectations. PMID- 27393216 TI - A disposable, continuous-flow polymerase chain reaction device: design, fabrication and evaluation. AB - Polymerase Chain Reaction (PCR) is used to amplify a specific segment of DNA through a thermal cycling protocol. The PCR industry is shifting its focus away from macro-scale systems and towards micro-scale devices because: micro-scale sample sizes require less blood from patients, total reaction times are on the order of minutes opposed to hours, and there are cost advantages as many microfluidic devices are manufactured from inexpensive polymers. Some of the fastest PCR devices use continuous flow, but they have all been built of silicon or glass to allow sufficient heat transfer. This article presents a disposable polycarbonate (PC) device that is capable of achieving real-time, continuous flow PCR in a completely disposable polymer device in less than 13 minutes by thermally cycling the sample through an established temperature gradient in a serpentine channel. The desired temperature gradient was determined through simulations and validated by experiments which showed that PCR was achieved. Practical demonstration included amplification of foot-and-mouth disease virus (FMDV) derived cDNA. PMID- 27393217 TI - Effects of anatomical changes on pencil beam scanning proton plans in locally advanced NSCLC patients. AB - BACKGROUND AND PURPOSE: Daily anatomical variations can cause considerable differences between delivered and planned dose. This study simulates and evaluates these effects in spot-scanning proton therapy for lung cancer patients. MATERIALS AND METHODS: Robust intensity modulated treatment plans were designed on the mid-position CT scan for sixteen locally advanced lung cancer patients. To estimate dosimetric uncertainty, deformable registration was performed on their daily CBCTs to generate 4DCT equivalent scans for each fraction and to map recomputed dose to a common frame. RESULTS: Without adaptive planning, eight patients had an undercoverage of the targets of more than 2GyE (maximum of 14.1GyE) on the recalculated treatment dose from the daily anatomy variations including respiration. In organs at risk, a maximum increase of 4.7GyE in the D1 was found in the mediastinal structures. The effect of respiratory motion alone is smaller: 1.4GyE undercoverage for targets and less than 1GyE for organs at risk. CONCLUSIONS: Daily anatomical variations over the course of treatment can cause considerable dose differences in the robust planned dose distribution. An advanced planning strategy including knowledge of anatomical uncertainties would be recommended to improve plan robustness against interfractional variations. For large anatomical changes, adaptive therapy is mandatory. PMID- 27393215 TI - Serotonin controls initiation of locomotion and afferent modulation of coordination via 5-HT7 receptors in adult rats. AB - KEY POINTS: Experiments on neonatal rodent spinal cord showed that serotonin (5 HT), acting via 5-HT7 receptors, is required for initiation of locomotion and for controlling the action of interneurons responsible for inter- and intralimb coordination, but the importance of the 5-HT system in adult locomotion is not clear. Blockade of spinal 5-HT7 receptors interfered with voluntary locomotion in adult rats and fictive locomotion in paralysed decerebrate rats with no afferent feedback, consistent with a requirement for activation of descending 5-HT neurons for production of locomotion. The direct control of coordinating interneurons by 5-HT7 receptors observed in neonatal animals was not found during fictive locomotion, revealing a developmental shift from direct control of locomotor interneurons in neonates to control of afferent input from the moving limb in adults. An understanding of the afferents controlled by 5-HT during locomotion is required for optimal use of rehabilitation therapies involving the use of serotonergic drugs. ABSTRACT: Serotonergic pathways to the spinal cord are implicated in the control of locomotion based on studies using serotonin type 7 (5-HT7 ) receptor agonists and antagonists and 5-HT7 receptor knockout mice. Blockade of these receptors is thought to interfere with the activity of coordinating interneurons, a conclusion derived primarily from in vitro studies on isolated spinal cord of neonatal rats and mice. Developmental changes in the effects of serotonin (5-HT) on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5-HT7 receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5-HT7 receptor blockade on voluntary overground locomotion and on locomotion without afferent input from the moving limb (fictive locomotion) in adult animals. Intrathecal injections of the selective 5-HT7 antagonist SB269970 in adult intact rats suppressed locomotion by partial paralysis of hindlimbs. This occurred without a direct effect on motoneurons as revealed by an investigation of reflex activity. The antagonist disrupted intra- and interlimb coordination during locomotion in all intact animals but not during fictive locomotion induced by stimulation of the mesencephalic locomotor region (MLR). MLR-evoked fictive locomotion was transiently blocked, then the amplitude and frequency of rhythmic activity were reduced by SB269970, consistent with the notion that the MLR activates 5-HT neurons, leading to excitation of central pattern generator neurons with 5-HT7 receptors. Effects on coordination in adults required the presence of afferent input, suggesting a switch to 5-HT7 receptor mediated control of sensory pathways during development. PMID- 27393218 TI - A randomised controlled trial of Caphosol mouthwash in management of radiation induced mucositis in head and neck cancer. AB - PURPOSE: This phase III, non-blinded, parallel-group, randomised controlled study evaluated the efficacy of Caphosol mouthwash in the management of radiation induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radical (chemo)radiotherapy. PATIENTS AND METHODS: Eligible patients were randomised at 1:1 to Caphosol plus standard oral care (intervention) or standard oral care alone (control), stratified by radiotherapy technique and use of concomitant chemotherapy. Patients in the intervention arm used Caphosol for 7weeks: 6weeks during and 1-week post-radiotherapy. The primary endpoint was the incidence of severe OM (CTCAE ?grade 3) during and up to week 8 post radiotherapy. Secondary endpoints include pharyngeal mucositis, dysphagia, pain and quality of life. RESULTS: The intervention (n=108) and control (n=107) arms were well balanced in terms of patient demographics and treatment characteristics. Following exclusion of patients with missing data, 210 patients were available for analysis. The incidence of severe OM did not differ between the intervention and control arms (64.1% versus 65.4%, p=0.839). Similarly, no significant benefit was observed for other secondary endpoints. Overall, compliance with the recommended frequency of Caphosol was low. CONCLUSION: Caphosol did not reduce the incidence or duration of severe OM during and after radiotherapy in HNC. PMID- 27393219 TI - Hypothalamic-pituitary GnRH/LH axis activity is affected by salsolinol in sheep during lactation: Effects of intracerebroventricular infusions of salsolinol and its antagonizing analogue. AB - The aim of the study was to test the hypothesis that salsolinol, a derivative of dopamine, is involved in the regulation of hypothalamic-pituitary gonadotropic (GnRH/LH) axis activity in lactating sheep. In the first experiment performed on sheep during the fifth week of lactation, a structural analogue of salsolinol (1 MeDIQ) was infused into the third brain ventricle (IIIv) to antagonize its action within the central nervous system (CNS). A push-pull perfusion of the infundibular nucleus/median eminence was performed simultaneously, and blood samples were collected from the jugular vein. In the second experiment, sheep received infusions of salsolinol into the IIIv, 48 hours after the weaning of their 8-week-old lambs. Blood samples were collected during the experimental periods, and the anterior pituitary (AP) tissue was dissected immediately after the end of the experiment. Perfusate GnRH concentration (experiment 1), plasma LH concentration (experiments 1 and 2), and relative LHbeta mRNA levels in the AP tissue (experiment 2) were assayed. Blocking of salsolinol action in the CNS of lactating sheep caused a significant (P < 0.001) decrease in the perfusate GnRH concentrations in comparison with controls. Treatment with 1-MEDIQ also significantly decreased (P < 0.001) the LH concentration in the blood plasma. In turn, salsolinol infused 48 hours after lamb weaning significantly (P < 0.001) increased plasma LH concentration, reflected in the significant (P < 0.05) increase in the amplitude of LH pulses in the treated sheep as compared to the control animals. There was no significant difference in the relative levels of LHbeta-subunit mRNA in the AP between control and salsolinol-infused sheep. The results lead to a conclusion that salsolinol affects the secretory activity of the GnRH/LH axis in sheep during lactation. Whether salsolinol infused into the IIIv evokes this stimulatory effect by itself or by modulation of other regulatory systems needs to be clarified. PMID- 27393220 TI - Changes in blood pressure, heart rate, and blood profile in mares during the last 3 months of gestation and the peripartum period. AB - In this study, peripartum changes in complete blood count, plasma electrolyte concentrations, blood pressure, heart rate, and heart rate variability (HRV) were determined in pregnant Warmblood mares (n = 10). Blood was collected from Days 245 to 330 of gestation (phase A), 2Days 3 to 1 before foaling (phase B), repeatedly within 12 hours after foaling (phase C), and on Days 1 to 3 postpartum (phase D). On the same days as blood collection, blood pressure and cardiac beat to-beat intervals were measured and time domain HRV variables were calculated. Blood pressure decreased during the past 3 months of gestation, reached a nadir at foaling and increased rapidly thereafter (P < 0.001). Heart rate increased in phase A, reached a maximum in phase B, and decreased directly after foaling (P < 0.001) while HRV increased transiently after foaling (P < 0.001). The number of polymorphonuclear granulocytes was higher during phases B, C, and D than that during phase A (P < 0.001) and total leukocyte numbers peaked in phase C (P < 0.001). Erythrocyte counts and hematocrit increased immediately after foaling with a rapid decrease thereafter (P < 0.001), while plasma total protein was highest 1 hour after foaling (P < 0.001). Sodium and chloride concentrations increased from phases A to C and decreased in phase D (P < 0.001). Calcium concentrations were lowest immediately after foaling. In conclusion, changes in cardiovascular function and a transient hemoconcentration occur in peripartum mares. These changes may favor adequate uterine perfusion. PMID- 27393221 TI - Lymphocytic foci in the endometrium of pregnant dairy cows: Characterization and association with reduced placental weight and embryonic loss. AB - Lymphocytic foci (also known as lymphoid aggregates or tertiary lymphoid structures) form within the bovine endometrium after antigenic challenge. Their presence in the pregnant uterus provides evidence for a chronic inflammatory condition perhaps arising from an early postpartum uterine infection. The chronic inflammation that includes the foci could explain greater embryonic loss in dairy cows with early postpartum uterine disease. The objectives were to characterize the size and location of the foci in the pregnant uterus, determine their composition using immunohistochemistry, and associate their presence with the development of the pregnancy and embryonic loss. Pregnant cows (n = 43) were slaughtered on days 28, 35, or 42 of pregnancy. Uterine tissue was collected and processed for histologic and immunohistochemical analysis. The number of small (<100 micron diameter), intermediate (100-250 micron diameter), and large (>250 micron diameter) foci was counted. The number of cows averaging 0, 0.1 to 1, 1.1 to 2, and more than 2 foci per section (small, intermediate, and large; combined) was 7 (16%), 14 (33%), 11 (26%), and 11 (26%), respectively. The average number of small and intermediate foci found in the histologic sections was greater in cows with evidence of uterine infection postpartum (P < 0.05). Lymphocytic foci were distributed within the caruncle and the intercaruncular tissue and comprised a core of CD3-positive cells (T cells) surrounding CD79-positive cells (B cells). The number of lymphocytic foci was correlated with a total inflammation score (on the basis of the total number of inflammatory cells in the endometrium; r(2) = 0.49; P < 0.001) and a fibrosis score (based on the extent of fibrosis in the endometrium; r(2) = 0.33; P < 0.001). Cows with a high foci count (averaging more than 0.5 foci per section) had lesser (P < 0.01) placental weight on Day 42 of pregnancy. There was no effect of foci count on placental weight on Day 28 or 35. Two cows with embryonic loss were in the highest quartile for foci count. In conclusion, cows with chronic inflammation as evidenced by a large number of lymphocytic foci had reduced placental weight during pregnancy. The number of foci in pregnant cows was associated with early postpartum uterine disease. Whether the foci themselves are inhibitory to pregnancy development or are associated with other bacteriological, morphological, or biochemical changes to the uterus that lead to infertility will need to be investigated. PMID- 27393222 TI - Crocetin improves the quality of in vitro-produced bovine embryos: Implications for blastocyst development, cryotolerance, and apoptosis. AB - The aim of this work was to assess the effect of supplementation of bovine culture medium with the natural antioxidant crocetin on in vitro blastocyst development and quality. This was evaluated as cryotolerance, apoptosis index, and total cells number and allocation. Abattoir-derived oocytes were matured and fertilized in vitro according to standard procedure. Twenty hours after IVF, presumptive zygotes were cultured in synthetic oviduct fluid medium, supplemented with 0, 1, 2.5, and 5 MUM crocetin (experiment 1) at 39 degrees C under humidified air with 5% CO2, 7% O2, and 88% N2. On Day 7, embryo yields were assessed and the blastocysts were vitrified by Cryotop method in 16.5% ethylene glycol, 16.5% DMSO, and 0.5 M sucrose. Finally, blastocysts produced on Day 8 in the absence (control) and presence of 1 MUM crocetin were used for terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and differential staining to evaluate, respectively, the apoptotic rate and the allocation of cells into inner cell mass (ICM) and trophectoderm (TE) lineages (experiment 2). Embryo development was higher in the 1 MUM crocetin group compared to the control, both in terms of total embryo output (37.7 +/- 4.2%, 52.9 +/- 6.3%, 40.9 +/- 7.6%, and 42.4 +/- 8.7%, respectively, with 0, 1, 2.5, and 5 MUM; P < 0.01) and grade 1 and 2 blastocysts (33.6 +/- 4.9%, 46.1 +/- 7.3%, 37.8 +/- 7.9%, and 39.4 +/- 7.9%, respectively, with 0, 1, 2.5, and 5 MUM; P < 0.05). Moreover, the percentage of fast-developing embryos increased in 1 MUM crocetin group compared to the control (23.4 +/- 4.7%, 32.7 +/- 6.6%, 27.2 +/- 6.6%, and 30.1 +/- 7.2%, respectively, with 0, 1, 2.5, and 5 MUM; P < 0.05). In addition, the enrichment of culture medium with 1 MUM crocetin improved embryo cryotolerance compared to the control, as indicated by higher hatching rates recorded after 48 hours postwarming culture (46.5% vs. 60.4%; P < 0.05). Furthermore, 1 MUM crocetin decreased both the average number (9.9 +/- 0.4 vs. 7.1 +/- 0.3) and the percentage of apoptotic cells (7.1 +/- 0.4 vs. 4.2 +/- 0.2) in blastocysts compared to the control (P < 0.01). However, no differences were recorded in the average number of ICM, TE, and total cells between 1 MUM crocetin and control groups. In conclusion, the enrichment of bovine culture medium with 1 MUM crocetin increased both blastocyst yield and quality, as indicated by the improved chronology of embryo development, increased resistance to cryopreservation, and reduced incidence of apoptosis. PMID- 27393223 TI - [Not Available]. PMID- 27393224 TI - [Not Available]. PMID- 27393225 TI - [Not Available]. PMID- 27393226 TI - [Not Available]. PMID- 27393227 TI - [Not Available]. PMID- 27393228 TI - [Not Available]. PMID- 27393229 TI - [Anaphylactic Shock Induced by Injectable Form of Glucantime(r) following a Previous Sensitization by Cutaneous Way]. PMID- 27393230 TI - [Danazol and Portal Vein Thrombosis: one Case Report]. PMID- 27393231 TI - [Hand-foot Syndrome Induced by Methotrexat]. PMID- 27393232 TI - Socioeconomic Segregation in Large Cities in France and the United States. AB - Past cross-national comparisons of socioeconomic segregation have been undercut by lack of comparability in measures, data, and concepts. Using IRIS data from the French Census of 2008 and the French Ministry of Finance as well as tract data from the American Community Survey (2006-2010) and the U.S. Department of Housing and Urban Development Picture of Subsidized Households, and constructing measures to be as similar as possible, we compare socioeconomic segregation in metropolitan areas with a population of more than 1 million in France and the United States. We find much higher socioeconomic segregation in large metropolitan areas in the United States than in France. We also find (1) a strong pattern of low-income neighborhoods in central cities and high-income neighborhoods in suburbs in the United States, but varying patterns across metropolitan areas in France; (2) that high-income persons are the most segregated group in both countries; (3) that the shares of neighborhood income differences that can be explained by neighborhood racial/ethnic composition are similar in France and the United States; and (4) that government-assisted housing is disproportionately located in the poorest neighborhoods in the United States but is spread across many neighborhood income levels in France. We conclude that differences in government provision of housing assistance and levels of income inequality are likely important contributing factors to the Franco-U.S. difference in socioeconomic segregation. PMID- 27393233 TI - The Effect of Schooling on Mortality: New Evidence From 50,000 Swedish Twins. AB - By using historical data on about 50,000 twins born in Sweden during 1886-1958, we demonstrate a positive and statistically significant relationship between years of schooling and longevity. This relation remains almost unchanged when exploiting a twin fixed-effects design to control for the influence of genetics and shared family background. This result is robust to controlling for within twin-pair differences in early-life health and cognitive ability, as proxied by birth weight and height, as well as to restricting the sample to MZ twins. The relationship is fairly constant over time but becomes weaker with age. Literally, our results suggest that compared with low levels of schooling (less than 10 years), high levels of schooling (at least 13 years of schooling) are associated with about three years longer life expectancy at age 60 for the considered birth cohorts. The real societal value of schooling may hence extend beyond pure labor market and economic growth returns. From a policy perspective, schooling may therefore be a vehicle for improving longevity and health, as well as equality along these dimensions. PMID- 27393234 TI - Effect of weight loss induced by energy restriction on measures of arterial compliance: A systematic review and meta-analysis. PMID- 27393235 TI - Message from the Editors - New Instructions to Authors. PMID- 27393236 TI - The first molluscan TRIM9 is involved in the negative regulation of NF-kappaB activity in the Hong Kong oyster, Crassostrea hongkongensis. AB - TRIM proteins are a group of highly conserved proteins participating in a variety of biological processes such as regulation of development, apoptosis, and innate immunity. However, the functions of these proteins in the mollusk are still poorly understood. In the present study, a TRIM9 homolog (named ChTRIM9) was first identified from a transcript-ome library in the Hong Kong oyster Crassostrea hongkongensis. The full-length cDNA of ChTRIM9 is 2928 bp and has a predicted Open Reading Frame ORF) encoding 721 amino acids, encoding a putative 80.2 kDa protein. SMART analysis indicated that ChTRIM9 contains the three typical TRIM domains, a RING finger, two B-boxes, and a coiled-coil domain in the N-terminal region, whereas the C-terminal region contains a SPRY domain. qRT-PCR analysis revealed a ubiquitous presence of ChTRIM9, with the highest expression in the gills. Upon bacterial challenge in vivo, the ChTRIM9 transcripts in hemocytes were significantly down-regulated, indicating its involvement in signal transduction in immune response of oysters. Furthermore, ChTRIM9 was found to be localized mainly in the cytoplasm, and its over-expression inhibited the transcriptional activity of the NF-kappaB gene in HEK293T cells, demonstrating its negative role in regulating NF-kappaB signaling. PMID- 27393237 TI - Effects of dietary live and heat-inactive baker's yeast on growth, gut health, and disease resistance of Nile tilapia under high rearing density. AB - In this study, the effects of baker's yeast as probiotics was evaluated in Nile tilapia reared at high density. Juvenile tilapia were distributed to tanks at high density (436 fish/m(3)) and fed with basal diet (CK) or diets supplemented with live (LY) or heat-inactivated yeast (HIY). Another group of fish reared at low density (218 fish/m(3)) and fed with basal diet was also included (LowCK). After 8 weeks of feeding, growth, feed utilization, gut microvilli morphology, digestive enzymes, and expressions of hsp70 and inflammation-related cytokines in the intestine were assessed. Intestinal microbiota was investigated using 16S rRNA gene pyrosequencing. Fish were challenged with Aeromonas hydrophila to evaluate disease resistance. High rearing density significantly decreased the growth, feed utilization, microvilli length, and disease resistance of fish (CK versus LowCK). Moreover, the intestinal hsp70 expression was increased in fish reared at high density, supporting a stress condition. Compared to CK group, supplementation of live yeast significantly increased gut microvilli length and trypsin activity, decreased intestinal hsp70 expression, and enhanced resistance of fish against A. hydrophila (reflected by reduced intestinal alkaline phosphatase activity 24 h post infection). The gut microbiota was not markedly influenced by either rearing density or yeast supplementation. Heat-inactivated yeast (HIY) didn't display the beneficial effects observed in LY except an increase in gut trypsin activity, suggesting the importance of yeast viability and thus secretory metabolites of yeast. In conclusion, live baker's yeast may alleviate the negative effects induced by crowding stress, and has the potential to be used as probiotics for tilapia reared at high density. PMID- 27393238 TI - Mixed population genomics support for the central marginal hypothesis across the invasive range of the cane toad (Rhinella marina) in Australia. AB - Understanding factors that cause species' geographic range limits is a major focus in ecology and evolution. The central marginal hypothesis (CMH) predicts that species cannot adapt to conditions beyond current geographic range edges because genetic diversity decreases from core to edge due to smaller, more isolated edge populations. We employed a population genomics framework using 24 235-33 112 SNP loci to test major predictions of the CMH in the ongoing invasion of the cane toad (Rhinella marina) in Australia. Cane toad tissue samples were collected along broad-scale, core-to-edge transects across their invasive range. Geographic and ecological core areas were identified using GIS and habitat suitability indices from ecological niche modelling. Bayesian clustering analyses revealed three genetic clusters, in the northwest invasion-front region, northeast precipitation-limited region and southeast cold temperature-limited region. Core-to-edge patterns of genetic diversity and differentiation were consistent with the CMH in the southeast, but were not supported in the northeast and showed mixed support in the northwest. Results suggest cold temperatures are a likely contributor to southeastern range limits, consistent with CMH predictions. In the northeast and northwest, ecological processes consisting of a steep physiological barrier and ongoing invasion dynamics, respectively, are more likely explanations for population genomic patterns than the CMH. PMID- 27393239 TI - Type IV-pili dependent motility is co-regulated by PilSR and PilS2R2 two component systems via distinct pathways in Myxococcus xanthus. AB - Myxococcus xanthus is an environmental bacterium with two forms of motility. One type, known as social motility, is dependent on extension and retraction of Type IV pili (T4P) and production of extracellular polysaccharides (EPS). Several signaling systems have been linked to regulation of T4P-dependent motility. In particular, expression of the pilin subunit pilA requires the PilSR two-component signaling system (TCS). A second TCS, PilS2R2, encoded within the same locus that encodes PilSR, has also been linked to M. xanthus T4P-dependent motility. We demonstrate that PilSR and PilS2R2 regulate M. xanthus T4P-dependent motility through distinct pathways. Consistent with known roles of PilSR, our results indicate that the primary function of PilSR is to regulate expression of pilA. In contrast, PilS2 and PilR2 have little to no affect on PilA protein levels. However, deletion of pilR2 resulted in a reduction of assembled pili, significant decreases in EPS production and loss of T4P-dependent motility. Furthermore, the pilR2 mutation led to increased production of outer membrane vesicles (OMV). Collectively, we propose that PilS2R2 is required for proper assembly of T4P and regulation of OMV production, and hypothesize that production of these vesicles is related to M. xanthus motility. PMID- 27393240 TI - Characteristics of temporal changes in communities where dynamics differ between species. AB - Communities with different phenotypic variation among species can have identical species abundance distributions, although their temporal dynamics may be very different. By using stochastic species abundance models, both the lognormal and beta prime abundance distributions can be obtained with either homogeneous or heterogeneous dynamics among species. Assuming that anthropogenic activity disturbs the communities such that species' carrying capacities are decreasing deterministically, the structure of the communities are studied using simulations. In order to construct homogeneous communities with reasonable variation in abundance, the parameter values describing the dynamics of the species can be unrealistic in terms of long return times to equilibrium. Species in heterogeneous communities can have stronger density regulation, while maintaining the same variation in abundance, by assuming heterogeneity in one of the dynamical parameters. The heterogeneity generates variation in carrying capacity among species, while reducing the temporal stochasticity. If carrying capacity decreases, changes in community structure occur at a much slower rate for the homogeneous compared to the heterogeneous communities. Even over short time periods, the difference in response to deterministic changes in carrying capacity between homogeneous and heterogeneous community models can be substantial, making the heterogeneous model a recommended starting point for community analysis. PMID- 27393242 TI - Corrigendum to "Fluctuations in Trypanosoma cruzi discrete typing unit composition in two naturally infected triatomines: Mepraia gajardoi and M. spinolai after laboratory feeding" [Acta Trop. (2016) 9-14]. PMID- 27393241 TI - Serum 25-hydroxyvitamin D level and incident type 2 diabetes in older men, the Osteoporotic Fractures in Men (MrOS) study. AB - The association between vitamin D status and diabetes risk is inconsistent among observational studies, and most of the available studies have been with women. In the present study we investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and incident type 2 diabetes (T2D) in older men (>=65years old) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study enrolled from March 2000 to April 2002. Baseline 25(OH)D levels were available in 1939 subjects without prevalent T2D. Clinical information, body mass index (BMI) and other factors related to T2D were assessed at the baseline visit. Incident diabetes, defined by self-report and medication use, was determined over an average follow-up of 6.4years. At baseline, participants were, on average, 73.3 (+/-5.7) years old, had a mean BMI in the overweight range (27.2kg/m(2)+/-3.6) and had total serum 25(OH)D of 26.1ng/ml (+/-8.3). Incident diabetes was diagnosed in 139 subjects. Cox regression analysis showed a trend toward a protective effect of higher 25(OH)D levels with a lower risk of T2D (HR 0.87, 95% CI: 0.73-1.04 per 1 SD increase of 25(OH)D). After adjusted for BMI and other potential confounders, the relationship between 25(OH)D levels and incident diabetes was further attenuated (HR 1.03, 95% CI 0.85-1.25). No significant difference in the incidence of diabetes emerged after analyzing study subjects according to baseline 25(OH)D quartiles. In conclusion, 25(OH)D levels were not associated with incident T2D in older men. PMID- 27393243 TI - Cryopreservation of lipid bilayers by LEA proteins from Artemia franciscana and trehalose. AB - The capacity of Late Embryogenesis Abundant (LEA) proteins and trehalose to protect liposomes against freezing-induced damage was examined by measuring the leakage of 5(6)-carboxyfluorescein (CF). Liposomes were prepared to simulate the lipid compositions of the inner leaflet of the plasma membrane, outer mitochondrial membrane (OMM), and inner mitochondrial membrane (IMM). Two recombinant LEA proteins belonging to Group 3 (AfrLEA2 and AfrLEA3m) were expressed and purified from embryos of Artemia franciscana. Only OMM-like liposomes were significantly protected by AfrLEA2 and AfrLEA3m against freeze thaw damage; at the highest protein:lipid mass ratio tested, leakage of CF was 56.3% of control with AfrLEA3m and 29.3% with AfrLEA2. By comparison, trehalose provided protection to all compositional types. The greatest stabilization during freezing occurred when trehalose was present on both sides of the bilayer. When mitochondria isolated from rat liver were freeze-thawed in trehalose solution, the OMM remained intact based on the absence of increased oxygen consumption when cytochrome c was added during oxidative phosphorylation (OXPHOS). Respiratory control ratios (OXPHOS/LEAK) were depressed by only 30% after freeze-thawing in trehalose compared to non-frozen controls, which indicated some retention of OXPHOS capacity by the IMM. Trehalose then was loaded into the matrix (0.24 MUmol/mg mitochondrial protein) by transient opening of the permeability transition pore, a procedure optimized for retention of OMM integrity. Surprisingly, respiratory control ratios were not improved after freeze-thawing with external plus matrix trehalose, when compared to external trehalose alone. This result could perhaps be explained by insufficient accumulation of matrix trehalose. PMID- 27393244 TI - The feasibility and safety of cryoablation as an adjuvant therapy with transurethral resection of bladder tumor: A pilot study. AB - BACKGROUND: The potential for transurethral resection (TUR) to result in residual tumors in patients with muscle invasive or high-risk non-muscle invasive bladder cancer (NMIBC) may affect local recurrence or progression. This study attempted to evaluate the feasibility and safety of cryoablation as an adjuvant therapy with TUR to treat bladder tumor. METHODS: Patients who met inclusion criteria between December 2014 and August 2015 in our institute was included. The inclusion criteria were as followed: 1) urothelial carcinoma; 2) non-muscle invasive bladder cancer or 3) stage T2 muscle invasive bladder cancer meeting with the following two conditions, solitary and less than 3 cm in size. Ten patients underwent TUR followed by immediate transurethral cryoablation of the tumor resection bed. All patients underwent pathological re-evaluation during follow-up cystoscopy. RESULTS: The cryoablation was successfully performed without bladder perforation during the procedures. No grade II-V complications were observed. Among these patients, two had T2a stage tumors, three had T1 stage tumors and five had Ta stage tumors. The median follow-up of cases was 9 months (range 9-14 months). During follow-up, tumor recurrence was observed in three patients. Only one recurrence occurred in the primary tumor site. CONCLUSIONS: Cryoablation as an adjuvant therapy with TUR for bladder tumors was feasible and safe. The potential benefit was to eliminate the residual tumor to the greatest extent. PMID- 27393245 TI - Effect of cyclodextrin-loaded cholesterol conjugates on plasma membrane viability of Piau swine breed frozen/thawed spermatozoa. AB - The objective of this study was to investigate the effect of cyclodextrin-loaded cholesterol conjugates addition to freezing extenders on plasma membrane viability of frozen-thawed spermatozoa of the Piau swine breed. Twenty semen samples were used from five males. The freezing extender was based on lactose-egg yolk extender, added to 2% glycerol, 3% dimethylacetamide. The addition of cyclodextrin-loaded cholesterol conjugates was performed after centrifugation, when semen was diluted with the cooling extender. Four groups were subjected to the following treatment: without addition (group 1); 1.5 mg of cyclodextrin loaded cholesterol/120 * 10(6) sperm (group 2); 1.5 mg of cyclodextrin-loaded cholestanol/120 * 10(6) sperm (group 3); 1.5 mg of cyclodextrin-loaded desmosterol/120 * 10(6) sperm (group 4). To check post-thawing sperm quality sperm motility and sperm morphology evaluation were used. Additionally, to check sperm viability the hypoosmotic swelling test, supravital staining, and fluorescent assay were used. The mean values recorded for total sperm motility of semen immediately after thawing were 54.5 +/- 5.8, 55.5 +/- 5.3, 53.7 +/- 6.7, and 52.5 +/- 6.6% respectively for groups one to four, without difference between themselves (p > 0.05). Regarding fluorescent assay the results were 28.3 +/- 13.2, 26.9 +/- 12.2, 22.2 +/- 11.4, and 32.0 +/- 15.3% respectively for groups one to four, also without difference between groups (p > 0,05). Similarly, complementary tests for evaluating the integrity and functionality of the plasma membrane showed no difference between treatments (p > 0.05). In conclusion, use of cyclodextrin-loaded cholesterol conjugates added to the plasma membrane of sperm did not demonstrate any additive effect on increasing and/or maintaining sperm motility. PMID- 27393246 TI - [Not Available]. AB - OBJECTIVE: To analyse drugs inducing hyperglycemia by using data reported to the French spontaneous reporting system and recorded in the French PharmacoVigilance Database (FPVD). METHODS: All cases with a report of hyperglycemia and/or diabetes in the French database between 1985 and 2008 were included in the study. We estimated the risk of hyperglycemia linked to drugs by the case/non-case method. Cases were reports including hyperglycemia and non cases all other reports. This risk was estimated through calculation of reporting odds ratios (ROR). RESULTS: During this period, 1219 reports including the words "hyperglycemia and/or diabetes" were registered (0.34% of the database). This adverse drug reaction occurred 1 fold over 4 in diabetics or as a part of HIV infection. Effect was "serious" in approximatively 50% of cases.We found an increase of risk during exposition with methylprednisolone [ROR=43.5; 95% CI (37.3-50.8)], tacrolimus [ROR=25; 95% CI (17.9-34.8)], olanzapine [ROR=19.9; 95% CI (14.9-26.5)], prednisone [ROR=18.9; 95% CI (15.7-22.8)] or pentamidine [ROR=15.4; 95% CI (8.2-28.3)]. CONCLUSION: Drug classes most frequently found in FPVD linked to hyperglycemia are antiretroviral, steroidal anti-inflammatory, second generation neuroleptic, immunosuppressive and diuretic drugs. PMID- 27393247 TI - Preparatory state and postural adjustment strategies for choice reaction step initiation. AB - A loud auditory stimulus (LAS) presented simultaneously with a visual imperative stimulus can reduce reaction time (RT) by automatically triggering a movement prepared in the brain and has been used to investigate a movement preparation. It is still under debate whether or not a response is prepared in advance in RT tasks involving choice responses. The purpose of the present study was to investigate the preparatory state of anticipatory postural adjustments (APAs) during a choice reaction step initiation. Thirteen young adults were asked to step forward in response to a visual imperative stimulus in two choice stepping conditions: (i) the responding side is not known and must be selected and (ii) the responding side is known but whether to initiate or inhibit a step response must be selected. LAS was presented randomly and simultaneously with the visual imperative stimulus. LAS significantly increased the occurrence rates of inappropriately initiated APAs while reducing the RTs of correct and incorrect trials in both task conditions, demonstrating that LAS triggered the prepared APA automatically. This observation suggests that APAs are prepared in advance and withheld from release until the appropriate timing during a choice reaction step initiation. The preparatory activity of APAs might be modulated by the inhibitory activity required by the choice tasks. The preparation strategy may be chosen for fast responses and is judged most suitable to comply with the tasks because inappropriately initiated APAs can be corrected without making complete stepping errors. PMID- 27393248 TI - Saccade adaptation in young people diagnosed with Attention Deficit Hyperactivity Disorder Combined Type. AB - Growing evidence suggests Attention Deficit Hyperactivity Disorder (ADHD) often co-occurs with Autism Spectrum Disorder (ASD), and a better understanding of the nature of their overlap, including at a neurobiological level, is needed. Research has implicated cerebellar-networks as part of the neural-circuitry disrupted in ASD, but little research has been carried out to investigate this in ADHD. We investigated cerebellar integrity using a double-step saccade adaptation paradigm in a group of male children age 8-15 (n=12) diagnosed with ADHD-Combined Type (-CT). Their performance was compared to a group of age and IQ-matched typically developing (TD) controls (n=12). Parent reported symptoms of ADHD-CT and ASD were measured, along with motor proficiency (Movement ABC-2). We found, on average, the adaptation of saccade gain was reduced for the ADHD-CT group compared to the TD group. Greater saccadic gain change (adaptation) was also positively correlated with higher Movement ABC-2 total and balance scores among the ADHD-CT participants. These differences suggest cerebellar networks underlying saccade adaptation may be disrupted in young people with ADHD-CT. Though our findings require further replication with larger samples, they suggest further research into cerebellar dysfunction in ADHD-CT, and as a point of neurobiological overlap with ASD, may be warranted. PMID- 27393250 TI - The impact of abacus training on working memory and underlying neural correlates in young adults. AB - Abacus-based mental calculation (AMC) activates the frontoparietal areas largely overlapping with the working memory (WM) network. Given the critical role of WM in cognition, how to improve WM capability has attracted intensive attention in past years. However, it is still unclear whether WM could be enhanced by AMC training. The current research thus explored the impact of AMC training on verbal and visuospatial WM, as well as the underlying neural basis. Participants were randomly assigned to an abacus group and a control group. Their verbal WM was evaluated by digit/letter memory span (DMS/LMS) tests, and visuospatial WM was assessed by a visuospatial n-back task. Neural activity during the n-back task was examined using functional MRI. Our results showed reliable improvements of both verbal and visuospatial WM in the abacus group after 20-day AMC training but not in the control. In addition, the n-back task-induced activations in the right frontoparietal circuitry and left occipitotemporal junction (OTJ) declined as a result of training. Notably, the decreases in activity were positively correlated with performance gains across trained participants. These results suggest AMC training not only improves calculating skills but also have the potential to promote individuals' WM capabilities, which is associated with the functional plasticity of the common neural substrates. PMID- 27393249 TI - Oxidative stress in the development, maintenance and resolution of paclitaxel induced painful neuropathy. AB - Paclitaxel is a first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Previous preclinical studies indicate mitochondrial dysfunction and oxidative stress are associated with this disorder; however no direct assessment of reactive oxygen species (ROS) levels and antioxidant enzyme activity in sensory neurons following paclitaxel has been undertaken. As expected, repeated low doses of systemic paclitaxel in rats induced long-lasting pain behaviour with a delayed onset, akin to the clinical scenario. To elucidate the role of ROSinthe development and maintenance ofpaclitaxel-inducedpainful neuropathy, we have assessed ROS and antioxidant enzyme activity levels in the nociceptive system in vivo at three key behavioural time-points; prior to pain onset (day 7), peak pain severity and pain resolution. In isolated dorsal root ganglia (DRG) neurons, ROS levels were unchanged following paclitaxel-exposure in vitro or in vivo. ROS levels were further assessed in DRG and spinal cord in vivo following intrathecal MitoTracker(r)RedCM-H2XRos administration in paclitaxel /vehicle-treated rats. ROS levels were increased at day 7, specifically in non peptidergic DRG neurons. In the spinal cord, neuronally-derived ROS was increased at day 7, yet ROS levels in microglia and astrocytes were unaltered. In DRG, CuZnSOD and glutathione peroxidase (GPx) activity were increased at day 7 and peak pain time-points, respectively. In peripheral sensory nerves, CuZnSOD activity was increased at day 7, and at peak pain, MnSOD, CuZnSOD and GPx activity were increased. Catalase activity was unaltered in DRG and saphenous nerves. These data suggest that neuronally-derived mitochondrial ROS, accompanied with an inadequate endogenous antioxidant enzyme response, are contributory factors in paclitaxel-induced painful neuropathy. PMID- 27393252 TI - Parkinson subtype-specific Granger-causal coupling and coherence frequency in the subthalamic area. AB - Previous work on Parkinson's disease (PD) has indicated a predominantly afferent coupling between affected arm muscle activity and electrophysiological activity within the subthalamic nucleus (STN). So far, no information is available indicating which frequency components drive the afferent information flow in PD patients. Non-directional coupling e.g. by measuring coherence is primarily established in the beta band as well as at tremor frequency. Based on previous evidence it is likely that different subtypes of the disease are associated with different connectivity patterns. Therefore, we determined coherence and causality between local field potentials (LFPs) in the STN and surface electromyograms (EMGs) from the contralateral arm in 18 akinetic-rigid (AR) PD patients and 8 tremor-dominant (TD) PD patients. During the intraoperative recording, patients were asked to lift their forearm contralateral to the recording side. Significantly more afferent connections were detected for the TD patients for tremor-periods and non-tremor-periods combined as well as for only tremor periods. Within the STN 74% and 63% of the afferent connections are associated with coherence from 4-8Hz and 8-12Hz, respectively. However, when considering only tremor-periods significantly more afferent than efferent connections were associated with coherence from 12 to 20Hz across all recording heights. No difference between efferent and afferent connections is seen in the frequency range from 4 to 12Hz for all recording heights. For the AR patients, no significant difference in afferent and efferent connections within the STN was found for the different frequency bands. Still, for the AR patients dorsal of the STN significantly more afferent than efferent connections were associated with coherence in the frequency range from 12 to 16Hz. These results provide further evidence for the differential pathological oscillations and pathways present in AR and TD Parkinson patients. PMID- 27393251 TI - Deletion of the murine ATP/UTP receptor P2Y2 alters mechanical and thermal response properties in polymodal cutaneous afferents. AB - P2Y2 is a member of the P2Y family of G protein-coupled nucleotide receptors that is widely co-expressed with TRPV1 in peripheral sensory neurons of the dorsal root ganglia. To characterize P2Y2 function in cutaneous afferents, intracellular recordings from mouse sensory neurons were made using an ex vivo preparation in which hindlimb skin, saphenous nerve, dorsal root ganglia and spinal cord are dissected intact. The peripheral response properties of individual cutaneous C fibers were analyzed using digitally controlled mechanical and thermal stimuli in male P2Y2(+/+) and P2Y2(-/-) mice. Selected sensory neurons were labeled with Neurobiotin and further characterized by immunohistochemistry. In wildtype preparations, C-fibers responding to both mechanical and thermal stimuli (CMH or CMHC) preferentially bound the lectin marker IB4 and were always immunonegative for TRPV1. Conversely, cells that fired robustly to noxious heat, but were insensitive to mechanical stimuli, were TRPV1-positive and IB4-negative. P2Y2 gene deletion resulted in reduced firing by TRPV1-negative CMH fibers to a range of heat stimuli. However, we also identified an atypical population of IB4 negative, TRPV1-positive CMH fibers. Compared to wildtype CMH fibers, these TRPV1 positive neurons exhibited lower firing rates in response to mechanical stimulation, but had increased firing to noxious heat (43-51 degrees C). Collectively, these results demonstrate that P2Y2 contributes to response properties of cutaneous afferents, as P2Y2 deletion reduces responsiveness of conventional unmyelinated polymodal afferents to heat and appears to result in the acquisition of mechanical responsiveness in a subset of TRPV1-expressing afferents. PMID- 27393253 TI - Gender differences of peripheral plasma and liver metabolic profiling in APP/PS1 transgenic AD mice. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment. Currently, there is less knowledge of the involvement of the peripheral biofluid/organ in AD, compared with the central nervous system. In addition, with reported high morbidity in women in particular, it has become very important to explore whether gender difference in the peripheral metabolome is associated with AD. Here, we investigated metabolic responses of both plasma and liver tissues using an APP/PS1 double mutant transgenic mouse model with NMR spectroscopy, as well as analysis from serum biochemistry and histological staining. Fatty acid composition from plasma and liver extracts was analyzed using GC-FID/MS. We found clear gender differences in AD transgenic mice when compared with their wild-type counterparts. Female AD mice displayed more intensive responses, which were highlighted by higher levels of lipids, 3-hydroxybutyrate and nucleotide-related metabolites, together with lower levels of glucose. These observations indicate that AD induces oxidative stress and impairs cellular energy metabolism in peripheral organs. Disturbances in AD male mice were milder with depletion of monounsaturated fatty acids. We also observed a higher activity of delta-6-desaturate and suppressed activity of delta-5-desaturate in female mice, whereas inhibited stearoyl-CoA-desaturase in male mice suggested that AD induced by the double mutant genes results in different fatty acids catabolism depending on gender. Our results provide metabolic clues into the peripheral biofluid/organs involved in AD, and we propose that a gender-specific scheme for AD treatment in men and women may be required. PMID- 27393254 TI - Understanding intentional actions from observers' viewpoints: A social neuroscience perspective. AB - When we see others, we also try to 'see' their unobservable states of minds, such as beliefs, desires, and intentions. We carefully monitor others' actions, as we assume that those actions are outward manifestations of their internal states. Actors and observers can have divergent views on the cause of the same actions. Critically, it is often the observers' view that affects important decisions in social life, from deciding the optimal level of cooperation to judging moral responsibility and court's decisions. Thus, the judgment about intentionality and agency in others' actions determines the way in which the observer deals with the actor. The primate brain has two separate neural systems that function in understanding others' actions and intentions. The mirror system is activated by others' visible actions and predicts their physical consequences in goal terms, whereas the mentalizing system is primarily involved in the prediction of others' intentions and upcoming actions regardless of whether others' actions are directly observable or not. The functional roles of the two systems have sometimes been described as mutually independent or even oppositional. I propose a hypothesis that the two systems may collaborate closely for judging the sense of other-agency. PMID- 27393255 TI - Spectrophotometric Assay for Superoxide Dismutase Based on the Reduction of Highly Water-soluble Tetrazolium Salts by Xanthine-Xanthine Oxidase. AB - Two novel highly water-soluble tetrazolium salts, WST-1 (4-[3-(4-iodophenyl)-2-(4 nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate sodium salt) and WST-8 (4 [3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate sodium salt) were applied to the assay of superoxide dismutase (SOD). The superoxide anion generated by xanthine/xanthine oxidase (XO) reduced WST-1 and WST-8 to water-soluble formazans which exhibited absorbance maxima at 438 and 460 nm, respectively. The rates of reduction were linearly related to the XO activity, and reduction was inhibited by SOD. Complete inhibition by SOD of the reduction of both WST-1 and WST-8 was achieved, suggesting that these WSTs were not reduced with XO. WST-1 was found more useful than WST-8 because it had shown higher sensitivity which was apparently not dependent on the assay pH value in the range pH 8.0-10.2. These properties of WST-1 are ideal for the spectrophotometric assay of SOD in an aqueous system. PMID- 27393256 TI - 9-Oxooctadeca-10,12-dienoic Acids as Acetyl-CoA Carboxylase Inhibitors from Red Pepper (Capsicum annuum L.). AB - A methanol extract of red pepper showed potent acetyl-CoA carboxylase inhibitory activity. The active principles were isolated and identified as (E, E)- and (E, Z)-9-oxooctadeca-10,12-dienoic acids by instrumental analyses. The IC50 values of the compounds were 1.4*10(-6) and 1.5*10(-6) M, respectively, their activity being nearly sixty-times higher than that of the common fatty acids themselves. A comparative study of the structure-activity relationship among their related compounds showed that the inhibitory activity was influenced neither by the position and species of the oxygen functional group in the middle of the alkyl chain nor by the configurations of the double bonds. However, it was found that the presence of double bonds between the terminal carboxyl and the mid-chain oxygen functional group lowered the inhibitory activity which could be recovered by hydrogenation of the double bonds. PMID- 27393257 TI - Synthesis and Fungicidal Activities of 4,5-Dihydro-7H-pyrano[3,4-c]isoxazole Derivatives. AB - 4,5-Dihydro-7H-pyrano[3,4-c]isoxazoles (II and III) with an o-chlorophenyl or p chlorophenyl group at C-7 were synthesized and the effect of substitution at C-3 of II and III on fungicidal activity was investigated in vivo. When the substituent at C-3 of II and III was CH2Br, CH=NOMe, CH=NOEt or CH=NO-allyl, the fungicidal effect was significant and selectively high on wheat leaf rust and barley powdery mildew at 250 ppm. Compound IId with the CH2Br substituent at C-7 showed high fungicidal activity against rice blast, providing more than 90% control of the disease at 2 ppm. PMID- 27393258 TI - Reducing-agents-mediated Solubilization and Activation of Debranching Enzyme (Pullulanase) in Rice Flour. AB - The effects of reducing agents on solubilization and activation of the debranching enzyme (pullulanase) were examined using rice flour. The activity of the debranching enzyme was observed in a buffer solution (pH 7.5) in which rice flour was incubated together with thiol-reducing reagents, (dithiothreitol, 2 mercaptoethanol etc.), but there was only low activity in the absence of reducing agents. Immunochemical measurement and the specific activity of the enzyme showed that the activation caused by the reductant was due to solubilization of the enzyme protein besides the enzyme activation. PMID- 27393259 TI - Biosynthetic Relationship between Acutumine and Dechloroacutumine in Menispermum dauricum Root Cultures. AB - The biosynthetic relationship between acutumine 1 and dechloroacutumine 2 was studied using (13)C-labeled tyrosine and (3)H-labeled 2 as tracers. (13)C-NMR spectra of (13)C-labeled 1 and 2 showed that the alkaloids, each composed of two molecules of tyrosine, are derived from the same biosynthetic pathway. Feeding Menispermum dauricum (Menispermaceae) roots, cultured in a chloride-enriched medium, with (3)H-labeled 2 demonstrated that 1 is the only alkaloid metabolite of 2. Conversion (5%) of the exogenously applied 2, taken up by the roots, into 1 showed that 2 is the precursor of 1. Incomplete conversion of 2 into 1 suggests accumulation of the exogenously applied 2 in cell organelles and/or compartmentation of the enzymes involved in the biosynthesis of 1. PMID- 27393260 TI - A Rapid Method for Transformation of Carrot (Daucus carota L.) by Using Direct Somatic Embryogenesis. AB - Several genes that may be involved in embryogenesis have been isolated from somatic embryos of carrot by many workers. However, the function of these genes has not been discovered yet. As the first step toward finding the function of these genes, we established a rapid and efficient method for transformation of carrot by using direct embryogenesis from hypocotyl segments treated with 2,4 dichlorophenoxyacetic acid (2,4-D) for a short period. PMID- 27393261 TI - New Bitter Diterpenes, Rabdosianone I and II, Isolated from Isodon japonicus Hara. AB - The new bitter diterpenes, rabdosianone I (C20H24O5) and II (C22H28O6), were isolated from Isodon japonicus (Japanese name, enmeiso), and their structures were elucidated by spectroscopic methods. Electrophysiological experiments were performed to compare rabdosianone I with quinine. The taste responses of chorda tympani nerves to rabdosianone I were smaller than those to quinine in Wistar rats. PMID- 27393262 TI - Decreased IgE-binding with Wheat Gluten by Deamidation. AB - The major wheat allergens contain a number of glutamine residues, suggesting that deamidation would be a promising method to produce hypoallergenic wheat proteins. Gluten was deamidated by acid under various conditions. The 30%-, 50%- and 90% deamidated glutens were reacted with sera of patients allergic to wheat proteins. The results indicate that the reactivity was dramatically decreased according to the degree of deamidation. PMID- 27393263 TI - Purification and Properties of NAD(+)-dependent Sorbitol Dehydrogenase from Bacillus fructosus. AB - Sorbitol dehydrogenase (EC 1.1.1.14), which catalyzes the NAD(+)-linked interconversion of D-sorbitol and D-fructose, was purified and crystallized from cell-free extracts of Bacillus fructosus grown on D-sorbitol as a sole carbon source. The crystalline enzyme was homogeneous on disc electrophoresis and ultracentrifugation. The molecular weight was 102,000 by the sedimentation equilibrium method. The enzyme acted specifically on D-sorbitol, and showed an optimum pH at 9.0. The K m values for D-sorbitol and NAD(+) were 1.1*10(-2) M and 2.2*10(-4) M, respectively. The enzyme activity was inhibited by p chloromercuribenzoate, Ag(+), Hg(2+), and Cu(2+). PMID- 27393264 TI - Improvement of Peroxyl Radical Scavenging Bioassay Based on Bactericidal Action of tert-Butyl Peroxyl Radical. AB - An improved bioassay for measurement of peroxyl radical scavenging activity(1,2)) is described. The modifications included the use of (1) Enterococcus faecium strain S, (2) 25% dimethyl sulfoxide, (3) L-ascorbic acid for the termination of the bactericidal reaction, and (4) the concentration of antioxidants that gives 75% of the log (colony forming unit/ml) of the control reaction (without methemoglobin or tert-butyl hydroperoxide), for the expression of antioxidant activity. PMID- 27393265 TI - Effective Cloning of Unmarked DNA Fragments in the Bacillus subtilis 168 Genome. AB - The Bacillus subtilis 168 genome is being used to clone DNA segments, particularly unmarked DNA segments between the two available clones. To facilitate this cloning, a counter selection method was developed in which loss of a cI repressor gene rendered the host strain resistant to neomycin. This method is promoted to use the B. subtilis genome as a general cloning vehicle. PMID- 27393266 TI - Lithopedion: an unexpected finding. PMID- 27393267 TI - The impact of pregnancy on anti-HIV activity of cervicovaginal secretions. AB - BACKGROUND: Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition. OBJECTIVE: The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women. STUDY DESIGN: Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test. RESULTS: Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; P<.01), but infectivity was not different between groups (P>=.44). During the second and third trimesters, pregnant women experienced suppression of several cervicovaginal immune mediators that included human beta defensin-2; lactoferrin; macrophage inflammatory protein-3alpha; regulated on activation, normally T-cell expressed and secreted; and stromal cell-derived factor-1 (all P<=.05). The antimicrobial peptide elafin was significantly correlated with HIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant group (n=16). Secretory leukocyte protease inhibitor also was correlated significantly with infectivity across all visits, but in nonpregnant women only (P<=.03). CONCLUSION: Cervicovaginal secretions from both pregnant and nonpregnant women contain immune mediators that are associated with HIV infectivity in an in vitro assay; however, infectivity was not different between pregnant and nonpregnant groups. If pregnant women are at increased risk for HIV infection, it is unlikely to be mediated by alterations in the effectiveness of these protective secretions. PMID- 27393268 TI - Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 10-year outcomes from the randomized EMMY trial. AB - BACKGROUND: Since 1995 uterine artery embolization has been described as an alternative for hysterectomy in patients with symptomatic fibroids. Many studies including several randomized controlled trials established uterine artery embolization as a valuable treatment. These randomized controlled trials reported outcomes in terms of health-related quality of life, clinical outcomes, efficacy, and cost-effectiveness after 1, 2, and 5 years of follow-up. OBJECTIVE: The purpose of this study was to compare clinical outcome and health-related quality of life 10 years after uterine artery embolization or hysterectomy in the treatment of heavy menstrual bleeding caused by uterine fibroids in a randomized controlled trial. STUDY DESIGN: In all, 28 Dutch hospitals recruited patients with symptomatic uterine fibroids who were eligible for hysterectomy. Patients were 1:1 randomly assigned to uterine artery embolization or hysterectomy. The outcomes assessed at 10 years postintervention were reintervention rates, health related quality of life, and patient satisfaction, which were obtained through validated questionnaires. Study outcomes were analyzed according to original treatment assignment (intention to treat). RESULTS: A total of 177 patients were randomized from 2002 through 2004. Eventually 81 uterine artery embolization and 75 hysterectomy patients underwent the allocated treatment shortly after randomization. The remaining patients withdrew from the trial. The 10-year questionnaire was mailed when the last included patient had been treated 10 years earlier. The mean duration of follow-up was 133 months (SD 8.58) accompanied by a mean age of 57 years (SD 4.53). Questionnaires were received from 131 of 156 patients (84%). Ten years after treatment, 5 patients underwent secondary hysterectomy resulting in a total of 28 of 81 (35%) (24/77 [31%] after successful uterine artery embolization). Secondary hysterectomies were performed for persisting symptoms in all cases but 1 (for prolapse). After the initial treatment health-related quality of life improved significantly. After 10 years, generic health-related quality of life remained stable, without differences between both groups. The urogenital distress inventory and the defecation distress inventory showed a decrease in both groups, probably related to increasing age, without significant differences between study arms. Satisfaction in both groups remained comparable. The majority of patients declared being (very) satisfied about the received treatment: 78% of the uterine artery embolization group vs 87% in the hysterectomy group. CONCLUSION: In about two thirds of uterine artery embolization-treated patients with symptomatic uterine fibroids a hysterectomy can be avoided. Health-related quality of life 10 years after uterine artery embolization or hysterectomy remained comparably stable. Uterine artery embolization is a well-documented and less invasive alternative to hysterectomy for symptomatic uterine fibroids on which eligible patients should be counseled. PMID- 27393269 TI - Long-term functional outcomes following colorectal resection versus shaving for rectal endometriosis. AB - BACKGROUND: Two surgical approaches usually are used in the surgical management of deep infiltrating endometriosis of the rectum: the radical approach that mainly is based on colorectal resection and the conservative or symptom-guided approach that prioritizes conservation of the rectum. There are no data available that compare long-term functional digestive outcomes of 1 approach to the other. OBJECTIVE: The purpose of this study was to compare long-term digestive outcomes in women who were treated by either rectal shaving or colorectal resection for deep endometriosis infiltrating the rectum. STUDY DESIGN: A retrospective comparative study was performed. All women who were treated with surgery for deep endometriosis infiltrating the rectum by either shaving or colorectal resection at the University Hospital of Rouen from January 2005 to January 2010 were enrolled. Follow-up evaluation was carried out for a minimum of 5 years. Postoperative evaluation of digestive symptoms was performed by 4 standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index, the Knowles-Eccersley-Scott-Symptom score for constipation, the Wexner score for anal continence, and the Bristol Stool Score. Symptoms that were related to endometriosis, fertility, and disease recurrence were obtained from a specific questionnaire. RESULTS: A total of 77 women were included. Three women were lost to follow up (3.9%), and 3 were treated by disc excision (3.9%). The mean follow up time was 80+/-19 months. Forty-six women underwent conservative rectal shaving, and 25 women underwent colorectal resection. Patient characteristics and the severity of the disease were comparable in both groups. Patients who were treated by rectal shaving had significantly better Gastrointestinal Quality of Life Index values, lower Knowles-Eccersley-Scott-Symptom scores for postoperative constipation, and better anal continence. No statistically significant differences were revealed for postoperative pelvic pain. Rectal recurrence occurred in 8.7% of patients who were treated by conservative surgery: 4.3% underwent secondary colorectal resection and 4.3% were treated secondarily by rectal shaving. Consequently, avoiding a recurrence for merely 1 patient would have required 11 patients to undergo colorectal resection instead of shaving. CONCLUSION: Our data suggest that, in patients who are treated for rectal endometriosis, colorectal resection does not improve long-term postoperative functional outcomes when compared with rectal shaving. PMID- 27393270 TI - Embryo donation: national trends and outcomes, 2000 through 2013. AB - BACKGROUND: Limited published data exist detailing outcomes of donor embryo cycles. Patients and clinicians would benefit from information specific to donor embryo cycles to inform fertility treatment options, counselling, and clinical decision-making. OBJECTIVE: We sought to quantify trends in donor embryo cycles in the United States, to characterize donor embryo recipients, and to report transfer, pregnancy, and birth outcomes of donor embryo transfers. STUDY DESIGN: This retrospective cohort study of frozen donor embryo transfers uses data from Centers for Disease Control and Prevention National ART Surveillance System to quantify trends in the use of donor embryos and corresponding rates of pregnancy and live birth from 2000 through 2013. For 2007 through 2013, years reflective of current practice, rates of cancellation, pregnancy, miscarriage, live birth, singleton and twin live birth, and delivery of a full-term singleton infant of normal birthweight (>=37 weeks, >=2500 g) are reported. RESULTS: Among all frozen transfers from 2000 through 2013 (n = 391,662), the annual number of donor embryo transfers increased significantly from 332-1374, however the proportion of donor embryo transfers among all frozen transfers did not change significantly (2.3 2.6%). Both overall pregnancy and live birth rates per frozen donor embryo transfer increased significantly (33.3-49.1% and 26.5-40.8%, respectively) (P < .01). Among all initiated donor embryo cycles from 2007 through 2013 (n = 7289), the overall cancellation rate prior to transfer was 7.1%. Among all transfers from 2007 through 2013 (n = 6773), 3193 (47.2%) resulted in pregnancy and 2589 (38.2%) resulted in a live birth. Among all pregnancies, 535 (16.9%) resulted in a miscarriage. Among all live births, 1929 (74.5%) delivered a singleton of which 1482 (76.8%) were full term and normal birthweight. CONCLUSION: The increasing availability of donor embryos, low chance of cancellation, and increasing likelihood of achieving live birth can inform consumers and providers who are considering assisted reproductive technology options. Collection of data surrounding donated embryo formation would allow for additional studies that can elucidate predictors of success among donor embryo transfers. PMID- 27393271 TI - Diagnostic accuracy of fetal rhesus D genotyping using cell-free fetal DNA during the first trimester of pregnancy. AB - BACKGROUND: Rhesus D genotyping with cell-free fetal DNA currently is used throughout the world. Although this technique has spread rapidly, its optimal use is still a matter of debate. This screening test has been introduced mainly for the treatment of RhD-negative pregnant women during the third trimester of pregnancy, thereby avoiding systematic anti-D prophylaxis, yet such a strategy has proved cost-ineffective. Publications reporting on fetal RHD genotyping with cell-free DNA in maternal plasma, specifically during the first trimester of pregnancy, are scarce in the scientific literature. OBJECTIVE: This study sought to assess the performance of noninvasive fetal Rhesus D genotyping in the first trimester of pregnancy with a single-exon real-time polymerase chain reaction assay. STUDY DESIGN: This was a retrospective observational multicenter study. Cell-free fetal DNA was extracted from maternal blood of both nonimmunized and immunized women at 10-14 weeks of gestation. RHD sequence was determined by quantitative polymerase chain reaction, with amplification of exon 10. Results were compared with RhD phenotype data that were obtained by cord blood sampling of neonates. RESULTS: In total, 416 serum samples from RhD-negative pregnant women were collected during the first trimester of pregnancy. The test's overall sensitivity and specificity were 100% (95% confidence interval, 96.9-100.0) and 95.2% (95% confidence interval, 90.5-97.6), respectively. The negative and positive predictive values were 99.8% (95% confidence interval, 94.9-100.0) and 97.1% (95% confidence interval, 94.2-98.6), respectively. Fetal RHD status was inconclusive in 9 cases (2.2%). CONCLUSION: Noninvasive fetal RHD determination by single-exon quantitative polymerase chain reaction during the first trimester of pregnancy exhibits high accuracy. PMID- 27393272 TI - [Not Available]. PMID- 27393273 TI - [Not Available]. AB - AIM: Study the epidemiological, clinical, biological and chronological drug rash with eosinophilia and systemic symptoms (DRESS) characteristic and indicate the implicated drugs. METHODS: We carried a retrospective study including all DRESS cases notified to the Pharmacovigilance Unit of Monastir. RESULTS: Our cohort of eleven patients had a median age of 40 years. Clinical examination revealed skin eruption and fever among all patients. Laboratory findings showed marked eosinophilia among all patients, hepatic cytolysis among eight patients and creatinin serum level increase among four patients. An interstitial pulmonary syndrome was noted among two patients. After culprit-drug withdrawal, outcomes were favorable for all patients. Skin tests were positive with carbamazepin and cefotaxim and negative with sulfasalazine, allopurinol and terbinafine. CONCLUSION: Throughout this paper, we point out the contribution of skin tests to identify implicated drug in inducing DRESS and to testify cross reactivity and we point out the possibility of neosensitisation to a non related chemical drug after DRESS syndrome. PMID- 27393274 TI - Pharmacokinetics, Safety, and Efficacy of Chemoembolization with Doxorubicin Loaded Tightly Calibrated Small Microspheres in Patients with Hepatocellular Carcinoma. AB - PURPOSE: This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres <=100 MUm for hepatocellular carcinoma. MATERIALS AND METHODS: A pilot safety study was performed in 19 patients with size and dose escalation and then 52 patients were enrolled prospectively and randomly assigned to chemoembolization with TANDEMTM loaded with 150 or 100 mg of doxorubicin. RESULTS: The mean diameter of the tumors was 7.28 +/- 2.09 cm (range 4-12) and distribution dominant/multiple 51.9/48.1 %. Child A/B distribution was 32/20 (61.5/38.5 %) and etiology HBV/HCV/HBV/HCV hemochromatosis was 61.6/9.6/9.6/15.4 %. Twenty-five patients were assigned in the low and 27 in the high loading group. There was 1.92 % thirty-day mortality due to lesion rupture. Biliary damage was seen in 3 patients (5.7 %) in the high loading. Mean maximum plasma concentration of doxorubicin C max +/- SD was 284.9 +/- 276.2 ng/mL for the high and 108.5 +/- 77.6 ng/mL for the low loading (p < 0.001). According to m-RECIST overall objective response after two sessions reached 61.22 and 63.82 % at 6 months. Notably, complete target lesion response (CR) after the second session was observed in 28.57 % and maintained in 23.40 % at 6 months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6 months, 1 , 2, and 3 years was 98.08, 92.3, 88.46, and 82.6 %, respectively. OS and Progression-Free Survival did not demonstrate statistical significance between the two loading groups. CONCLUSION: Initial evidence shows that (a) TANDEMTM achieves high rates of local response and mid-term survival, (b) high loading provides no clinical benefit and is associated with biliary toxicity. PMID- 27393275 TI - Urinary MCP-1,HMGB1 increased in calcium nephrolithiasis patients and the influence of hypercalciuria on the production of the two cytokines. AB - The study aims to observe the urinary excretion of monocyte chemoattractant-1 (MCP-1) and high-mobility group box 1 (HMGB1) in patients with calcium nephrolithiasis and to determine the influence of hypercalciuria on the production of the two cytokines. 81 cases of patients with calcium nephrolithiasis (group CN) and 30 healthy controls (group C) were involved in this study. To observe the influence of urinary calcium on the excretion of those cytokines, the patients were subdivided according to their 24-h urinary calcium level: >=4 mg/kg/day (group H) and <4 mg/kg/day (group N). MCP-1 and HMGB1 in urina sanguinis were determined for all subjects. In addition, in vitro study was done to determine the production of the two cytokines and index of apoptosis and oxidative injuries in human kidney epithelial cells (HK-2) exposed to three high levels of calcium. Data showed that both urinary MCP-1 and HMGB1 in group CN were higher than that of group C. When the patients were subdivided, comparisons among the three groups showed that both MCP-1 and HMGB1 in group H and group N were higher than group C, but there was no significant statistical difference between the two stone groups. In vitro study, the apoptosis rate of cells, the lactate dehydrogenase activities, the hydrogen peroxide, and 8-isoprostane concentrations in the medium all increased in accordance with the increased concentration of calcium supplemented. Compared with the control, mRNA expressions of MCP-1 and HMGB1 in cells and the protein concentrations of the two cytokines in the medium of calcium-supplemented groups increased significantly. Results showed that urinary MCP-1 and HMGB1 increased in calcium nephrolithiasis patients and hypercalciuria might affect the identical pathways (through the reactive oxygen species) with other factors in stimulating the production of MCP-1 and HMGB1 in vivo. PMID- 27393276 TI - Renal stones composition in vivo determination: comparison between 100/Sn140 kV dual-energy CT and 120 kV single-energy CT. AB - The objective of this study is to compare in vivo, the accuracy of single-energy CT (SECT) and dual-energy CT (DECT) in renal stone characterization. Retrospective study approved by the IRB. 30 patients with symptomatic urolithiasis who underwent CT on a second-generation dual-source scanner with a protocol that included low-dose 120 kV scan followed by 100/Sn140 kV dual-energy scan have been included. Stone composition was classified as uric acid, cystine or calcium oxalates, and phosphates according to attenuation values at 120 kV and to 100/Sn140 kV attenuation ratios and compared with the infrared spectroscopy analysis. 50 stones were detected in 30 patients. SECT correctly assessed stone composition in 52 % of the cases, DECT in 90 %. Sensitivity, specificity, positive predictive value, and negative predictive value in differentiating uric acid vs. non-uric acid stones were 0.94, 0.72, 0.64, and 0.96 for SECT and 1.00, 0.94, 1.00, and 0.96 for DECT, respectively. DECT significantly performs better than SECT in characterising renal stones in vivo, and may represent a useful tool for treatment planning. PMID- 27393277 TI - Studies on DNA interaction of organotin(IV) complexes of meso-tetra(4 sulfonatophenyl)porphine that show cellular activity. AB - The interaction of the diorgano- and triorganotin(IV) derivatives of meso-tetra (4-sulfonatophenyl)porphine (Me2Sn)2TPPS, (Bu2Sn)2TPPS, (Me3Sn)4TPPS and (Bu3Sn)4TPPS to natural DNA was analysed (together with free meso-tetra-(4 sulfonatophenyl)porphine (TPPS4-) for comparison purposes). Particular attention was paid to (Bu3Sn)4TPPS, a species that shows significant cellular action. Preliminary tests were done on the solution properties of the organotin(IV) compounds (pKA and possible self-aggregation). Spectrophotometric and spectrofluorometric experiments showed that all the investigated organotin(IV) derivatives strongly interact with DNA, the binding energy depending on the dye steric hindrance. In all cases experimental data concur in indicating that external binding mode prevails. Interestingly, fluorescence quenching and viscosity experiments show that the Bu-containing species, and in particular (Bu3Sn)4TPPS, are able to noticeably alter the DNA conformation. PMID- 27393278 TI - Prognostic impact of RUNX1 and ETV6 gene copy number on pediatric B-cell precursor acute lymphoblastic leukemia with or without hyperdiploidy. AB - The ETV6/RUNX1 fusion gene is a valuable prognostic marker that is frequently observed in B-cell precursor acute lymphoblastic leukemia (B-cell ALL). However, the clinical significance of copy number aberrations in these genes remains unclear. In this study, the effects of various aberrations inETV6 and RUNX1 gene copy number on disease prognosis were evaluated in 21 pediatric patients diagnosed with B-cell ALL with/without t(12;21). The prognostic significance of changes in gene copy number of ETV6 or RUNX1 in the presence or absence of hyperdiploidy, trisomy 21, and t(12;21) translocation were also evaluated. RUNX1 gene copy number amplifications were detected in 83 % of the patients who lacked t(12;21) and in all of the patients with hyperdiploidy. Trisomy 21 was detected in 78 % of the patients with hyperdiploidy. Changes in ETV6 gene copy number were detected in patients who lacked both the t(12;21) translocation and RUNX1 gene copy number amplifications. However, RUNX1 gene copy number amplification and ETV6 deletion were observed in all of the patients with t(12;21). RUNX1 gene copy number amplification was associated with hyperdiploidy, but not with t(12;21). Thus, the evaluation of distinct FISH and cytogenetic patterns in patients with B cell ALL may strengthen the prognostic significance of changes in gene copy number. PMID- 27393280 TI - Planning of mandibular reconstructions based on statistical shape models. AB - PURPOSE: The reconstruction of large continuity defects of the mandible is a challenging task, especially when the shape of the missing part is not known prior to operation. Today, the surgical planning is based mainly on visual judgment and the individual skills and experience of the surgeons. The objective of the current study was to develop a computer-based method that is capable of proposing a reconstruction shape from a known residual mandible part. METHODS: The volumetric data derived from 60 CT scans of mandibles were used as the basis for the novel numerical procedure. To find a standardized representation of the mandible shapes, a mesh was elaborated that follows the course of anatomical structures with a specially developed topology of quadrilaterals. These standard meshes were transformed with defined mesh modifications toward each individual mandible surface to allow for further statistical evaluations. The data were used to capture the inter-individual shape variations that were considered as random field variations and mathematically evaluated with principal component analysis. With this information of the mandibular shape variations, an algorithm was developed that proposes shapes for reconstruction planning based on given residual mandible geometry parts. RESULTS: The accuracy of the novel method was evaluated on six different virtually defined continuity defects that were each created on three mandibles that were not part of the initial database. Virtual reconstructions showed sufficient accuracy of the algorithm for the planning of surgical reconstructions, with average deviations toward the actual geometry of [Formula: see text] mm for small missing parts and 5 mm for large hemi-lateral defects. CONCLUSIONS: The presented algorithm may be a valuable tool for the planning of mandibular reconstructions. The proposed shapes can be used as templates for computer-aided manufacturing, e.g., with 3D printing devices that use biocompatible materials. PMID- 27393279 TI - Low prognostic nutritional index predicts poor outcome in diffuse large B-cell lymphoma treated with R-CHOP. AB - Prognostic nutritional index (PNI), based on serum albumin concentration and the absolute peripheral lymphocyte count, has been used to predict survival in various tumors. Whether PNI can predict prognosis in patients with diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 253 patients with newly diagnosed DLBCL in the present study. The PNI was calculated as: albumin (g/L) + 5 * total lymphocyte count * 10(9)/L. All patients were divided in low and high groups according to the analysis of receiver operating characteristic (ROC) curve. Low PNI was associated with more unfavorable clinical features (p < 0.05). Patients with low PNI tended to have worse event-free survival (EFS) and overall survival (OS) (EFS, p = 0.001; OS, p < 0.001). For patients treated with R-CHOP, PNI proved to be predictive for survival (EFS, p = 0.001; OS, p < 0.001), while no significant effect was found in DLBCL patients who received CHOP chemotherapy (EFS, p = 0.496; OS, p = 0.125). Multivariate analysis showed that low PNI is an independent adverse predictor of OS and EFS, especially in DLBCL patients treated with R-CHOP. In conclusion, this study suggests that PNI is an effective prognostic factor in DLBCL patients treated with R-CHOP. PMID- 27393281 TI - Copy number variations and stroke. AB - Stroke is the third leading cause of death worldwide after heart disease and all forms of cancers. Monogenic disorders, genetic, and environmental risk factors contribute to damaging cerebral blood vessels and, consequently, cause stroke. Developments in genomic research led to the discovery of numerous copy number variants (CNVs) that have been recently identified as a new tool for understanding the genetic basis of many diseases. This review discusses the current understanding of the types of stroke, the existing knowledge on the involvement of specific CNVs in stroke as well as the limitations of the methods used for detecting CNVs like SNP-microarray. To confirm an unequivocally association between CNVs and stroke and extend the current findings, it would be desirable to use another methodology to detect smaller CNVs or CNVs in genomic regions poorly covered by this technique, for instance, CGH-array. PMID- 27393282 TI - Subclinical change of liver function could also provide a clue on prognosis for patients with spontaneous intracerebral hemorrhage. AB - Whether subclinical change of liver function is associated with outcome of spontaneous intracerebral hemorrhage remains to be an open question. A total of 639 patients of spontaneous intracerebral hemorrhage within 7 days from stroke onset were finally enrolled. Liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (BIL), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), albumin (ALB), and international normalized ratio (INR), were collected and collapsed into quartiles. The main outcomes were 30-day death, 90-day death, and 90-day poor outcome (modified Rankin Scale score of 3-6). Two adjusted model, Model 1 and Model 2 (Model 1 plus GCS score), were established to identify independent association between liver function indicators and ICH outcomes. The mortality rate was 19.9 % (127/639) at 30 days and 21.3 % (136/639) at 90 days. Rate of 90 day poor outcome was 51.5 % (329/639). Among liver function indicators, AST and ALP were associated with all the three outcomes, which did not alter significantly when adjusted by Model 1. After adjusted by Model 2, ALP was still associated with outcomes. Association between AST and outcomes was, however, weakened significantly by GCS score. In conclusions, among liver function indicators, AST and ALP were associated with outcomes after spontaneous intracerebral hemorrhage. PMID- 27393284 TI - In the Aftermath of the Storm Called Power Morcellation. PMID- 27393283 TI - Laparoscopic Imaging Techniques in Endometriosis Therapy: A Systematic Review. AB - Endometriosis is a common disease associated with pelvic pain and subfertility. Laparoscopic surgical treatment has proven effective in endometriosis, but is hampered by a high rate of recurrence. The aim of this systematic review was to evaluate the intraoperative identification of endometriosis by enhanced laparoscopic imaging techniques, focusing on sensitivity and specificity. A systematic review was conducted according to PRISMA guidelines in PubMed, Embase, Cochrane Library, and Web of Science. Published prospective studies reporting on enhanced laparoscopic imaging techniques during endometriosis surgery were included. General study characteristics and reported outcomes, including sensitivity and specificity, were extracted. Nine studies were eligible for inclusion. Three techniques were described: 5-ALA fluorescence (5-ALA), autofluorescence (AFI), and narrow-band imaging (NBI). The reported sensitivity of 5-ALA and AFI for identifying endometriosis ranged from 91% to 100%, compared with 48% to 69% for conventional white light laparoscopy (WL). A randomized controlled trial comparing NBI + WL with WL alone reported better sensitivity of NBI (100% vs 79%; p < .001). All 9 studies reported an enhanced detection rate of endometriotic lesions with enhanced imaging techniques. Enhanced imaging techniques are a promising additive for laparoscopic detection and treatment of endometriosis. The 5-ALA, AFI, and NBI intraoperative imaging techniques had a better detection rate for peritoneal endometriosis compared with conventional WL laparoscopy. None of the studies reported clinical data regarding outcomes. Future studies should address long-term results, such as quality of life, recurrence, and need for reoperation. PMID- 27393285 TI - Emerging Manifestations of Cesarean Scar Defect in Reproductive-aged Women. AB - The objective of this study was to evaluate the prevalence of cesarean scar defects and its clinical manifestations in reproductive-aged women. We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using keywords of "cesarean scar defect, uterine scar defect, uterine diverticulum niche, isthmocele, pouch, or sacculation" and their combination. Thirty-two trials met the inclusion criteria. Cesarean scar defects are commonly found on ultrasound examination (24%-88%). Their presence could be asymptomatic or related to postmenstrual spotting, postmenstrual bleeding, or infertility. The prevalence of this condition is related to the number of cesarean deliveries. Hysteroscopic repair of a cesarean scar defect or isthmoplasty is associated with an improvement in uterine bleeding in 59% to 100% of cases and a pregnancy rate of 77.8% to 100%. An improvement in uterine bleeding after vaginal repair occurred in 89% to 93.5% of cases. Laparoscopic repair led to uterine bleeding improvement in 86% of cases and a pregnancy rate of 86%. The association between cesarean scar defect and infertility, pelvic pain, and dysmenorrhea require more studies. Treatment of uterine scar defects should be performed after eliminating other causes of postmenstrual bleeding or infertility. Hysteroscopic isthmoplasty appears to be the most popular treatment. However, in the absence of randomized trials, the efficacy of different surgical approaches remains to be seen. Until we have concrete evidence, the treatment should be reserved for selective cases. PMID- 27393286 TI - Power Morcellation of Unsuspected High-grade Leiomyosarcoma Within an Inflated Containment Bag: 2-year Follow-up. AB - The diagnosis of an unsuspected leiomyosarcoma after hysterectomy for the treatment of a presumed benign leiomyoma is a rare but highly clinically significant event. In order to facilitate removal of large uterine specimens using a minimally invasive surgical approach, morcellation with extraction in pieces is often performed. In the event of unsuspected malignancy, this may result in abdominal dispersion of the tumor and contribute to poorer survival. In the present article, we report a case of contained power morcellation of an unsuspected high-grade leiomyosarcoma with 2 years of follow-up. Although further study is necessary, this technique may minimize the risk that women undergoing laparoscopic hysterectomy with morcellation have a worse prognosis when diagnosed with an unexpected malignancy. PMID- 27393287 TI - Laparoscopic Tubal Reanastomosis Using Barbed Sutures. AB - STUDY OBJECTIVE: To show a new technique of laparoscopic tubal reanastomosis using barbed sutures. DESIGN: Step-by-step explanation of the technique using videos. SETTING: Laparoscopic tubal reanastomosis is an effective procedure with a high success rate for reversal of tubal sterilization. Conventionally, 4 equidistant interrupted sutures are placed under a magnified view for laparoscopic tubal reanastomosis. This step demands high precision and requires a lot of skill and experience. We have tried to simplify this suturing technique by using barbed sutures because they do not require knotting. Two separate 5-0 Quill barbed sutures (Angiotech Puerto Rico Inc, Aguadilla, Puerto Rico) are used in this technique. The first suture is used for taking 6 and 3 o' clock stitches. The second suture is used for taking 9 and 12 o' clock stitches. With this technique, the purse-string effect on the tubal lumen is reduced. INTERVENTIONS: Laparoscopic tubal reanastomosis using 5-0 Quill barbed sutures (equivalent to United States Pharmacopeia suture size 6-0). CONCLUSION: This technique of laparoscopic tubal reanastomosis using barbed sutures is a feasible and simpler alternative to conventional suturing. PMID- 27393289 TI - [Medical examination: Preparation for ENT specialisation : Part 26]. PMID- 27393288 TI - Characterization of Lower Urinary Tract Symptoms Before and After Midurethral Sling Revision. AB - STUDY OBJECTIVE: To characterize outcomes in women undergoing surgical revision of a midurethral sling and characterize factors associated with satisfaction of revision. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: A urogynecology clinic at a large academic referral center. PATIENTS: Women undergoing surgical revision of synthetic mesh midurethral sling (index surgery). INTERVENTIONS: Chart review was performed to obtain baseline clinicodemographic information, operative notes, urodynamic parameters, and symptom-specific distress and impact questionnaire data. Eligible women were then sent follow-up questionnaires that assessed reasons for index surgery, presence of dyspareunia, symptom-specific distress and impact, and satisfaction after mesh midurethral sling surgery. MEASUREMENTS AND MAIN RESULTS: Of 144 eligible women, 69 (47.9%) responded, 15 (10.4%) declined participation or were deceased, and 59 (41.6%) did not respond. The mean time from index surgery was 22.2 +/- 14.0 months. Women with transobturator slings were more frequently revised for vaginal exposure (p = .003), whereas women with retropubic slings were more frequently revised for voiding dysfunction (p < .0001). Sixty-four percent of women were satisfied with surgery. Satisfied women had more improvement in pain (p = .04), dyspareunia (p < .001), and Patient Global Impression of Improvement questionnaire scores (p < .0001). Multivariable analysis showed that satisfaction decreased with increasing years in age (adjusted odds ratio = 0.95; 95% confidence interval, 0.90-0.99). CONCLUSION: Women who were satisfied with sling revision were younger and more likely to have resolution of pain and dyspareunia and improved Patient Global Impression of Improvement scores. This information may help to inform patients regarding expectations with regard to sling revision. PMID- 27393290 TI - [Erratum to: Medical and psychological aspects of the treatment of connatal dacryostenosis : Parental evaluation of their own and their child's stress]. PMID- 27393291 TI - [Surgical simulation on the lateral skull base]. AB - Critical neurovascular structures are confined in a small bony space at the lateral skull base. Thus, high quality of surgical training and planning of minimally invasive procedures is crucial. Simulation of lateral skull base procedures can improve motor skills, anatomical orientation, and complication management in a safe environment. Thus, simulation training can be beneficial for skull base surgeons. Minimally invasive interventions at the lateral skull base are under research, and several authors have presented approaches through single or multiple drilled ports. Precise planning and simulation of such interventions is essential because even submillimeter errors can lead to damage to critical anatomical structures. Therefore, high demands have been set for the accuracy of computer-assisted surgery. PMID- 27393292 TI - [The Freiburg monosyllable word test in postoperative cochlear implant diagnostics]. AB - BACKGROUND: The Freiburg monosyllable word test represents a central tool of postoperative cochlear implant (CI) diagnostics. OBJECTIVES: The objective of this study is to test the equivalence of different word lists by analysing word comprehension. For patients whose CI has been implanted for more than 5 years, the distribution of suprathreshold speech intelligibility outcomes will also be analysed. PATIENTS AND METHODS: In a retrospective data analysis, speech understanding for 626 CI users word correct scores were evaluated using a total of 5211 lists with 20 words each. RESULTS: The analysis of word comprehension within each list shows differences in mean and in the kind of distribution function. There are lists which show a significant difference of their mean word recognition to the overall mean. The Freiburg monosyllable word test is easy to administer at suprathreshold speech level for CI recipients, and typically has a saturation level above 80 %. CONCLUSION: The Freiburg monosyllable word test can be performed successfully by the majority of CI patients. The limited balance of the test lists elicits the conclusion that an adaptive test procedure with the Freiburg monosyllable test does not make sense. The Freiburg monosyllable test can be restructured by resorting all words across lists, or by omitting individual words of a test list to increase the reliability of the test. The results show that speech intelligibility in quiet should also be investigated in CI recipients al levels below 70 dB. PMID- 27393293 TI - [The new guideline "Treatment of Inflammatory Diseases of the Palatine Tonsils - Tonsillitis" : Impact in clinics and surgeries]. PMID- 27393294 TI - [Computer-controlled high-precision radiation]. AB - The irradiation of tumors in the brain is challenging due to the proximity of radiation sensitive critical structures and the tumors to be treated. In addition, irradiation above a certain level can cause irreversible damage to nerve tissue. The irradiation of benign and malignant brain tumors requires precise techniques to preserve critical structures while simultaneously administering a high radiation dose for maximum effectiveness. Therefore, stereotaxy, as a subspecialty of neurosurgery, has developed various irradiation techniques, e. g., intracerebral application of interstitial brachytherapy (SBT; stereotactic brachytherapy) and stereotactic radiosurgery (SRS). Due to the development of computer-controlled radiation techniques (e. g., Cyberknife) over the last 20 years, SRS has gained increasing importance. PMID- 27393295 TI - The ubiquitin-like modifier FAT10 in cancer development. AB - During the last years it has emerged that the ubiquitin-like modifier FAT10 is directly involved in cancer development. FAT10 expression is highly up-regulated by pro-inflammatory cytokines IFN-gamma and TNF-alpha in all cell types and tissues and it was also found to be up-regulated in many cancer types such as glioma, colorectal, liver or gastric cancer. While pro-inflammatory cytokines within the tumor microenvironment probably contribute to FAT10 overexpression, an increasing body of evidence argues that pro-malignant capacities of FAT10 itself largely underlie its broad and intense overexpression in tumor tissues. FAT10 thereby regulates pathways involved in cancer development such as the NF-kappaB- or Wnt-signaling. Moreover, FAT10 directly interacts with and influences downstream targets such as MAD2, p53 or beta-catenin, leading to enhanced survival, proliferation, invasion and metastasis formation of cancer cells but also of non-malignant cells. In this review we will provide an overview of the regulation of FAT10 expression as well as its function in carcinogenesis. PMID- 27393296 TI - Reply to Delanghe, Speeckaert, and De Buyzere: "The evolutionary adaptation of hemochromatosis associated mutations during the Neolithic". PMID- 27393298 TI - Erratum to: PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy. PMID- 27393297 TI - Central serous chorioretinopathy in primary hyperaldosteronism. AB - PURPOSE: To describe ophthalmological characteristics of 13 patients with primary hyperaldosteronism (PA). METHODS: Cross-sectional study. All patients underwent extensive ophthalmological examination. RESULTS: Thirteen PA patients (9 male, 4 female) were diagnosed with arterial hypertension for 11.0 +/- 11.2 years. Ophthalmological imaging revealed macular serous subretinal fluid (SRF) on optical coherence tomography in 2 patients (15 %). In one of these patients, bilateral chronic central serous chorioretinopathy (CSC) with polypoidal choroidal neovasculopathy was diagnosed, which was effectively treated with full dose photodynamic therapy. In the other patient with SRF and bilateral diffuse hyperfluorescent areas on fluorescein angiography, the SRF had decreased spontaneously after 6 weeks of follow-up. In 5 of the remaining patients (38 %), retinal pigment epithelium alterations resembling findings characteristic for CSC were seen on multimodal imaging. The mean subfoveal choroidal thickness was 290.2 +/- 65.0 MUm. CONCLUSIONS: Retinal abnormalities resembling (subclinical) CSC are common in patients with PA. These findings indicate that mineralocorticoid mediated pathways are involved in the pathogenesis of CSC. In CSC patients with hypertension of unknown origin, a diagnosis of PA should be considered. PMID- 27393299 TI - Erratum to: The methyl donor S-adenosylmethionine potentiates doxorubicin effects on apoptosis of hormone-dependent breast cancer cell lines. PMID- 27393300 TI - Comment on: "One-year GH replacement therapy reduces early cardiac target organ damage (TOD) in adult GHD patients" by Boschetti et al. PMID- 27393301 TI - Clinical vertebral fractures following denosumab discontinuation. PMID- 27393302 TI - Recurrent GDM and the development of type 2 diabetes have similar risk factors. PMID- 27393303 TI - Nonspecific binding of a frequently used vitamin D receptor (VDR) antibody: important implications for vitamin D research in human health. PMID- 27393304 TI - Monomeric Form of Peptidylarginine Deiminase Type I Revealed by X-ray Crystallography and Small-Angle X-ray Scattering. AB - Peptidylarginine deiminase (PAD; EC 3.5.3.15) is a post-translational modification enzyme that catalyzes the conversion of arginine in protein molecules to a citrulline residue in a Ca(2+)-dependent manner. In this study, we determined the structure of an active form of human PAD1 crystallized in the presence of Ca(2+) at 3.2-A resolution. Although human PAD2 and PAD4 isozymes were previously reported to form a head-to-tail homodimer, it is still unknown whether this quaternary structure is common to other PAD isozymes. The asymmetric unit of the crystal contained two PAD1 molecules; however, the head-to-tail dimeric form was not found. Small-angle X-ray scattering analyses revealed PAD1 to be a monomer in solution, while PAD3 was dimerized with a structure similar to PAD2 and PAD4. PAD1 was apparently different from the crystal structures of PAD2 and PAD4, with an elongated N-terminal loop that appears to prevent the formation of the homodimer. Of interest, the N-terminal loop occupied the substrate binding site of the adjacent PAD1 molecules in the crystal. Deimination of S100A3 peptides in vitro implied that PAD isozymes recognize the quaternary structure of S100A3. The substrate-accessible monomeric structure brought about by the extension of its N terminus may partly account for the highest tolerant substrate recognition of PAD1. This is the first ever report on the molecular structure of PAD1 demonstrating the unique monomeric form of the PAD isozyme. PMID- 27393305 TI - Chaperonin GroEL-GroES Functions as both Alternating and Non-Alternating Engines. AB - A double ring-shaped GroEL consisting of 14 ATPase subunits assists protein folding, together with co-chaperonin GroES. The dynamic GroEL-GroES interaction is actively involved in the chaperonin reaction. Therefore, revealing this dynamic interaction is a key to understanding the operation principle of GroEL. Nevertheless, how this interaction proceeds in the reaction cycle has long been controversial. Here, we directly imaged GroEL-GroES interaction in the presence of disulfide-reduced alpha-lactalbumin as a substrate protein using high-speed atomic force microscopy. This real-time imaging revealed the occurrence of primary, symmetric GroEL:GroES2 and secondary, asymmetric GroEL:GroES1 complexes. Remarkably, the reaction was observed to often branch into main and side pathways. In the main pathway, alternate binding and release of GroES occurs at the two rings, indicating tight cooperation between the two rings. In the side pathway, however, this cooperation is disrupted, resulting in the interruption of alternating rhythm. From various properties observed for both pathways, we provide mechanistic insight into the alternate and non-alternate operations of the two-engine system. PMID- 27393306 TI - Polysaccharide Degradation by the Intestinal Microbiota and Its Influence on Human Health and Disease. AB - Carbohydrates comprise a large fraction of the typical diet, yet humans are only able to directly process some types of starch and simple sugars. The remainder transits the large intestine where it becomes food for the commensal bacterial community. This is an environment of not only intense competition but also impressive cooperation for available glycans, as these bacteria work to maximize their energy harvest from these carbohydrates during their limited transit time through the gut. The species within the gut microbiota use a variety of strategies to process and scavenge both dietary and host-produced glycans such as mucins. Some act as generalists that are able to degrade a wide range of polysaccharides, while others are specialists that are only able to target a few select glycans. All are members of a metabolic network where substantial cross feeding takes place, as by-products of one organism serve as important resources for another. Much of this metabolic activity influences host physiology, as secondary metabolites and fermentation end products are absorbed either by the epithelial layer or by transit via the portal vein to the liver where they can have additional effects. These microbially derived compounds influence cell proliferation and apoptosis, modulate the immune response, and can alter host metabolism. This review summarizes the molecular underpinnings of these polysaccharide degradation processes, their impact on human health, and how we can manipulate them through the use of prebiotics. PMID- 27393308 TI - [Not Available]. PMID- 27393307 TI - [Not Available]. PMID- 27393309 TI - Protocolisation, Use and Development of Anti-Cancer Drugs in the Context of T2A (Case-Mix Based Payment System) Set-Up. AB - Drugs used in oncology represent more than half of the innovative and costly drugs which are not covered by a Group Homogene de Soins (DRG type classification) within the context of the case-mix based payment system (termed T2A). For these drugs, good practice reference guidelines have been drawn up by scientific societies and registration agencies. Recognised indications, relevant indications and situations where the treatment should not be prescribed are defined by the National Institute of Cancer. The reference guidelines should lead towards the good use of these drugs and allow the sick funds to control prescriptions. They should evolve with time, which means that bibliographic monitoring and independent expert opinion is necessary to update them as science provides new data. Manufacturers are involved in this process which in no case should undermine developmental efforts leading to registration. The objective of this protocolisation is to allow all patients early and legitimate access to drugs representing real therapeutic progress. These reference guidelines should be integrated into the life-cycle of a drug and should give rise to new developments allowing the good use of cancer products in situations which have been properly validated. PMID- 27393310 TI - [Not Available]. PMID- 27393311 TI - Two-photon imaging of cerebral hemodynamics and neural activity in awake and anesthetized marmosets. AB - BACKGROUND: Marmosets are a powerful, emerging model for human behavior and neurological disorders. However, longitudinal imaging modalities that visualize both cellular structure and function within the cortex are not available in this animal model. Hence, we implemented an approach to quantify vascular topology, hemodynamics, and neural activity in awake marmosets using two-photon microscopy (2PM). NEW METHOD: Marmosets were acclimated to a custom stereotaxic system. AAV1 GCaMP5G was injected into somatosensory cortex to optically indicate neural activity, and a cranial chamber was implanted. RESULTS: Longitudinal 2PM revealed vasculature and neurons 500MUm below the cortical surface. Vascular response and neural activity during sensory stimulation were preserved over 5 and 3 months, respectively, before optical quality deteriorated. Vascular remodeling including increased tortuosity and branching was quantified. However, capillary connectivity from arterioles to venules remained unchanged. Further, behavioral assessment before and after surgery demonstrated no impact on cognitive and motor function. Immunohistochemistry confirmed minimal astrocyte activation with no focal damage. Over 6 months, total cortical depth visualized decreased. When under anesthesia, the most prominent isoflurane-induced vasodilation occurred in capillaries and smaller arterioles. COMPARISON WITH EXISTING METHOD(S): These results demonstrate the capability to repeatedly observe cortical physiology in awake marmosets over months. CONCLUSIONS: This work provides a novel and insightful technique to investigate critical mechanisms in neurological disorders in awake marmosets without introducing confounds from anesthesia. PMID- 27393312 TI - High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. AB - Diets high in fat (HFD) are known to cause an immune response in the periphery as well as the central nervous system. In peripheral adipose tissue, this immune response is primarily mediated by macrophages that are recruited to the tissue. Similarly, reactivity of microglia, the innate immune cells of the brain, has been shown to occur in the hypothalamus of mice fed a high-fat diet. To characterize the nature of the microglial response to diets high in fat in a temporal fashion, we studied the phenotypic spectrum of hypothalamic microglia of mice fed high-fat diet for 3 days and 8 weeks by assessing their tissue reaction and inflammatory signature. While we observed a significant increase in Iba1+ myeloid cells and a reaction of GFAP+ astrocytes in the hypothalamus after 8 weeks of HFD feeding, we found the hypothalamic myeloid cell reaction to be limited to endogenous microglia and not mediated by infiltrating myeloid cells. Moreover, obese humans were found to present with signs of hypothalamic gliosis and exacerbated microglia dystrophy, suggesting a targeted microglia response to diet in humans as well. Notably, the glial reaction occurring in the mouse hypothalamus was not accompanied by an increase in pro-inflammatory cytokines, but rather by an anti-inflammatory reaction. Gene expression analyses of isolated microglia not only confirmed this observation, but also revealed a downregulation of microglia genes important for sensing signals in the microenvironment. Finally, we demonstrate that long-term exposure of microglia to HFD in vivo does not impair the cell's ability to respond to additional stimuli, like lipopolysaccharide. Taken together, our findings support the notion that microglia react to diets high in fat in a region-specific manner in rodents as well as in humans; however, this response changes over time as it is not exclusively pro-inflammatory nor does exposure to HFD prime microglia in the hypothalamus. PMID- 27393314 TI - Indigenous sheep breeds in Brazil: potential role for contributing to the sustainability of production systems. AB - Brazil has vocation for food production, both vegetable and animal, with the sheep industry having an expanding activity. However, productivity rates are often bellowing the possibilities of the country. Here, the roles the native breeds may develop in this expanding activity are described. Breeds considered are the hair breeds Santa Ines, Morada Nova, Somalis Brasileira, Cariri, and Rabo Largo, and the wool breeds Bergamacia Brasileira, Crioula Lanada, and Pantaneira. These breeds have arisen in environments that may be considered difficult for other (exotic) breeds, less adapted to the local conditions. The hair breeds emerged in a semi-arid environment, a hot and with low rainfall region, of the Northeast of Brazil. The Crioula Lanada is the only breed that originated in the South, in a subtropical region with cold winters. The genetic group Pantaneira had its origin in an environment with higher humidity, especially soil moisture. The Bergamacia Brasileira derived from the Italian Bergamasca breed, which was first introduced in northeastern Brazil. Animals from these breeds have been regarded as robust, with lower requirements for maintenance, resistant to worms, and easy to handle. On the other side, as they are generally smaller than the exotic breeds used for meat production, they are often considered as less productive. In this literature review, a possibility of valorizing them, both as purebred or in crossbreeding programs, especially for meat production is addressed. These breeds are part of the genetic, historical, and cultural heritage of Brazil, and if used properly, according to the different environments and production systems, they can also be very important in the development of the sheep industry. PMID- 27393315 TI - [Not Available]. AB - Advances in lung transplantation allow the women of childbearing age to consider becoming mothers. When planning to become pregnant, a therapeutic drug management of immunosuppressive drugs and associated therapies is required. It must take into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes encountered during pregnancy. Increasingly data are currently available on the management of immunosuppressive drugs and associated therapies during pregnancy. We report the case management of drug therapy before and during pregnancy in two patients after a lung or heart-lung transplantation. To prevent the emergence of complications for mother and child, a literature review has been necessary to manage drug therapies of each patient. PMID- 27393313 TI - Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue. AB - Secondary mitochondrial dysfunction is a feature in a wide variety of human protein aggregate diseases caused by mutations in different proteins, both in the central nervous system and in striated muscle. The functional relationship between the expression of a mutated protein and mitochondrial dysfunction is largely unknown. In particular, the mechanism how this dysfunction drives the disease process is still elusive. To address this issue for protein aggregate myopathies, we performed a comprehensive, multi-level analysis of mitochondrial pathology in skeletal muscles of human patients with mutations in the intermediate filament protein desmin and in muscles of hetero- and homozygous knock-in mice carrying the R349P desmin mutation. We demonstrate that the expression of mutant desmin causes disruption of the extrasarcomeric desmin cytoskeleton and extensive mitochondrial abnormalities regarding subcellular distribution, number and shape. At the molecular level, we uncovered changes in the abundancy and assembly of the respiratory chain complexes and supercomplexes. In addition, we revealed a marked reduction of mtDNA- and nuclear DNA-encoded mitochondrial proteins in parallel with large-scale deletions in mtDNA and reduced mtDNA copy numbers. Hence, our data demonstrate that the expression of mutant desmin causes multi-level damage of mitochondria already in early stages of desminopathies. PMID- 27393316 TI - Voluntary Wheel Running Reverses the Decrease in Subventricular Zone Neurogenesis Caused by Corticosterone. AB - Adult neurogenesis within the dentate gyrus (DG) of the hippocampus can be increased by voluntary exercise but is suppressed under stress, such as with corticosterone (CORT). However, the effects of exercise and CORT on the cell proliferation of the other traditional neurogenic site, the subventricular zone (SVZ), have been reported with controversial results. In addition, the cotreatment effects of voluntary exercise and CORT have not been investigated. This study aims to determine whether CORT can suppress cell proliferation in the SVZ and whether this can be reversed by voluntary exercise. In the present study, the effect of chronic (4 weeks) CORT treatment and wheel running simultaneously on the SVZ cell proliferation of adult Sprague-Dawley rats was examined. The results showed that cell proliferation indicated by bromodeoxyuridine (BrdU) was increased by voluntary wheel running, whereas it was decreased by CORT treatment within the SVZ of the rats without running. For the rats with both CORT treatment and wheel running, it was found that the number of BrdU-labeled cells was approximately at the same level as the vehicle control group. Furthermore, these proliferating cells expressed doublecortin (DCX), a migrating neuroblast marker. Wheel running increased the percentage of BrdU-labeled cells expressing DCX in the SVZ, whereas CORT treatment decreased this percentage. Thus, chronic injection of CORT can decrease the number of proliferating cells, while wheel running can reverse the decrease in cell proliferation within the SVZ to normal levels. In addition, CORT can suppress the cell differentiation within the SVZ, and this was alleviated by wheel running as indicated by the double labeling of BrdU and DCX. PMID- 27393317 TI - [Not Available]. AB - Treatment of Bronchial Superinfections: Data Related to Stability of Antibiotics in Portable Pumps. INTRODUCTION: Given many data about the stability of antibiotics in portable pump (elastomer) are lacking, this study was designed to make a point about available data and to evaluate the stability of antibiotics when exposed to temperature within 35 degrees C (average temperature measured in real conditions of use). MATERIAL AND METHODS: First, to collect information about the stability of antibiotics in portable pump and to confront them with the local antibiotics protocols dedicated to the treatment of bronchial superinfection in patients with cystic fibrosis; second, to evaluate the stability of piperacillin associated with tazobactam at 35 degrees C. RESULTS: While measured concentrations in tazobactam did not show significant variation during the study, piperacillin measurements showed a major reduction of concentration (up to 33%), both time and concentration related to. DISCUSSION: Such information must be pointed out to prescribers and patients to ensure a cold accumulator is placed in the pump can'ying-bag and to limit the duration of infusion to 24h with a single pump. CONCLUSION: This experimental program will keep on going with the stability study of both ticarcillin and cefsulodin in portable pump. PMID- 27393318 TI - [Not Available]. AB - The Optimal Dosing Times of Corticoids. The therapeutic use of Cortisol and its derivatives, anti-inflammatory corticoids, sets delicate problems to resolve because of Cortisol's physiological roles and its circadian rhythms. Cortisol and the majority of its derivatives have desirable and undesirable effects that are time-related administration. The chronothera- peutic optimisation to increase desirable effects and safety of corticoids is shown in the treatment of adrenocortical failure, congenital adrenal hyperplasia and asthma. The knowledge of physiological and physiopathological rhythms of asthma permitted to realize oral treatment optimisation by using a number of corticoids. This knowledge puts in a prominent position the advantages of ciclesonide: a new inhaled corticoid. A chronobiologic approach could be used in a classic optimisation which involves a molecule modification and inhalation like routes of administration. PMID- 27393319 TI - [Not Available]. AB - Analysis of Antiretroviral Drugs-Induced Adverse Elfects. In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting. PMID- 27393320 TI - Sickness Absence and Precarious Employment: A Comparative Cross-National Study of Denmark, Finland, Sweden, and Norway. AB - BACKGROUND: Precarious employment is a major social determinant of health and health inequalities with effects beyond the health of workers. OBJECTIVE: To investigate the association between precarious employment and sickness absence in 4 Nordic countries, Denmark, Finland, Norway, and Sweden. METHODS: Logistic regression analyses were conducted separately for each country on data from 4186 respondents aged 15-65 years in Denmark, Finland, Norway, and Sweden derived from the 2010 European Working Conditions Survey. Sickness absence was based on self reports and defined as absence of seven or more day per year. Precarious employment was operationalized as a multidimensional construct of indicators. Analyses were also conducted separately for men and women. RESULTS: The prevalence of sickness absence was lowest in Sweden (18%), and highest in Finland (28%). 3 precarious employment indicators were positively associated with sickness absence; the pattern being largely similar in the total sample. In the sex-disaggregated sample, 5 precarious employment indicators increased the likelihood of sickness absence; the pattern was heterogeneous, with women generally having significantly higher odds of sickness absence than men. "Low household income" and "sickness presenteeism" were strong predictors of sickness absence among both sexes in most of the 4 studied countries. Sickness absence varied between the Nordic countries in the sex-disaggregated analyses. CONCLUSION: Precarious employment indicators predicted sickness absence in the Nordic countries. Findings emphasize the need to prioritize informed and monitored collective bargaining for all workers, increase working time flexibility, and improving work conditions. PMID- 27393321 TI - Respiratory Morbidity among Indian Tea Industry Workers. AB - BACKGROUND: Indian tea industry workers are exposed to various exposures at their workplace. OBJECTIVE: To investigate the respiratory health of Indian tea industry workers. METHODS: We administered a respiratory questionnaire to and measured lung function in workers of 34 tea gardens and 46 tea factories. We used correlation matrices to test the association between their respiratory symptoms and lung functions. RESULTS: The garden workers complained of shortness of breath 3 times higher than the factory workers. However, nasal allergy was more predominant among the factory workers compared to garden workers (69.6% vs 41.2%, p=0.02). The factory workers had higher total (median 107.3% vs 92.9%, p=0.05, as measured by R at 5 Hz) and peripheral airway resistance (143.8% vs 61.1%, p=0.005, as measured by R at 5-20 Hz) than the garden workers. Respiratory symptoms were inversely associated with airway obstruction as measured by the ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and positively correlated with increased overall airway reactance among the workers. CONCLUSION: Respiratory symptoms and increased allergen susceptibility of Indian tea industry workers due to occupational exposures warrant routine systematic surveillance of their workplace air quality and health monitoring. PMID- 27393322 TI - Work Environment-Related Risk Factors for Leptospirosis among Plantation Workers in Tropical Countries: Evidence from Malaysia. AB - BACKGROUND: Leptospirosis is a zoonotic disease that is recognized as a re emerging global public health issue, especially in tropical and subtropical countries. Malaysia, for example, has increasingly registered leptospirosis cases, outbreaks, and fatalities over the past decade. One of the major industries in the country is the palm oil sector, which employs numerous agricultural workers. These laborers are at a particularly high risk of contracting the disease. OBJECTIVE: To identify the work environment-related risk factors for leptospirosis infection among oil palm plantation workers in Malaysia. METHODS: A cross-sectional study involving 350 workers was conducted. The participants were interviewed and administered a microscopic agglutination test. Seropositivity was determined using a cut-off titer of >=1:100. RESULTS: 100 of 350 workers tested positive for leptospiral antibodies, hence, a seroprevalence of 28.6% (95% CI 23.8% to 33.3%). The workplace environment related risk factors significantly associated with seropositive leptospirosis were the presence of cows in plantations (adjusted OR 4.78, 95% CI 2.76 to 8.26) and the presence of a landfill in plantations (adjusted OR 2.04, 95% CI 1.22 to 3.40). CONCLUSION: Preventing leptospirosis incidence among oil palm plantation workers necessitates changes in policy on work environments. Identifying modifiable factors may also contribute to the reduction of the infection. PMID- 27393323 TI - Validation of Multidimensional Persian Version of the Work-Family Conflict Questionnaire among Nurses. AB - BACKGROUND: Several instruments have so far been developed in English language to measure the level of work-family conflict and further validation is required for non-English speakers. OBJECTIVE: To test factorial structure and construct validity of the Persian version of work-family conflict scale among Iranian nurse. METHODS: This study was conducted among 456 Iranian nurses working at public hospitals in 17 provinces from March 2015 to September 2015. We used a self-administrated questionnaire to collect information. Exploratory factor analysis was run using SPSS 21. Then, construct validity was evaluated using confirmatory factor analysis (CFA), convergent validity, and discriminant validity by AMOS 21. RESULTS: Exploratory factor analysis extracted four dimensions that explained 65.5% of the variance observed. The results of confirmatory factor analysis showed that our data fitted the hypothesized four dimensional model of work-family conflict construct. The average variance extracted was used to establish convergent and discriminant validity. CONCLUSION: The Persian version of work-family conflict questionnaire is a valid and reliable instrument among Iranian nurses. PMID- 27393324 TI - Sharp Injury and Exposure to Blood and Body Fluids among Health Care Workers in Health Care Centers of Eastern Ethiopia. AB - BACKGROUND: Health care workers are facing certain occupational hazards because of sharp injury and exposure to human blood and body fluids as a result of handling wastes. Though much attention is paid for the protection of these workers, the number of exposures and injuries do not show a sign of decline from time to time. OBJECTIVE: To examine the occurrence of sharp injury and exposure to blood and body fluids in health care workers in health care centers in Ethiopia. METHODS: In a case-control study, a randomly selected sample of 65 health facilities with 391 cases and 429 controls were studied. Data were collected through a self-administered questionnaire. Detailed analysis of exposure among the health care workers was done by logistic regression analysis with generalized estimating equations model to control correlation effects of responses within the cluster of health facilities. RESULTS: The number of health care workers who got sharp injury was 217 (26.5%). 296 (36.1%) had exposure to blood and body fluids. Working at Harari region (adjusted OR 0.44, 95% CI 0.26 to 0.75) and East Hararghea (adjusted OR 0.61, 95% CI 0.40 to 0.94), being male (adjusted OR 0.56, 95% CI 0.44 to 0.91), and a being nurse (adjusted OR 0.188, 95% CI 0.06 to 0.63) were independent risk factors of the exposure. CONCLUSION: Regardless of the anticipated low self-reporting for exposure status, the number of health care workers reported having sharp injury and exposure to blood and body fluids was high. Such high exposures indicate that health care workers are at high risk of acquiring blood-borne viral infections such as hepatitis B, hepatitis C, and HIV. PMID- 27393325 TI - Workplace Violence and Gender Bias in Unorganized Fisheries of Udupi, India. AB - Fisheries industry in India is an unorganized sector of occupation where considerable proportion of workers is female. However, the prevalent gender inequality in terms of task allocation, wages, and other welfare facilities makes the men as dominant workforce. Furthermore, there are occasions when incidents of workplace violence take place. The present study was conducted to find the prevalence of workplace violence at worksite and study gender bias in such events. In a cross-sectional study 171 fishermen and fisherwomen were interviewed to collect information about workplace violence. The overall prevalence of workplace violence reported was 14.6%. This included 2 (8%) cases of physical assault, 1 (4%) case of sexual harassment of fisherwoman by her colleague and 22 (88%) cases of verbal abuse. A significant (p=0.002) association was found between gender and verbal abuse at the workplace. In conclusion, this study highlighted the occurrence of workplace violence among fishery workers in India. There was a gender bias towards females that can be attributed to male dominance in this occupation. PMID- 27393326 TI - Ergonomic Redesign of an Industrial Control Panel. AB - Operator's role in industrial control centers takes place in time, which is one of the most important determinants of whether an expected action is going to be successful or not. In certain situations, due to the complex nature of the work, the existing interfaces and already prepared procedures do not meet the dynamic requirements of operator's cognitive demands, making the control tasks unnecessarily difficult. This study was conducted to identify ergonomic issues with a specific industrial control panel, and redesign its layout and elements to enhance its usability. Task and link analysis methodologies were implemented. All essential functions and supporting operations were identified at the required trivial levels. Next, the weight of any possible link between the elements of the panel was computed as a composite index of frequency and importance. Finally, all components were rearranged within a new layout, and a computerized mockup was generated. A total of 8 primary tasks was identified, including 4 system failure handling tasks, switching between manual and automated modes, and 3 types of routine vigilance and control tasks. These tasks were broken down into 28 functions and 145 supporting operations, accordingly. Higher link values were observed between hand rest position and 2 elements. Also, 6 other components showed robust linkages. In conclusion, computer modeling can reduce the likelihood of accidents and near misses in industrial control rooms by considering the operators' misperception or mental burden and correcting poor design of the panels and inappropriate task allocation. PMID- 27393327 TI - Long-term Exposure to Extremely Low Frequency Electromagnetic Field and Melatonin Production by Blood Cells. PMID- 27393328 TI - Toxicological Effects Induced by Silver Nanoparticles in Zebra Fish (Danio Rerio) and in the Bacteria Communities Living at Their Surface. AB - The antimicrobial activity of silver nanoparticles (AgNP) makes them useful in a wide range of products although their environmental impact is still uncertain. The main goal of this study was to evaluate short-term effects induced by AgNP on gills oxidative status and bacterial communities living at the skin mucus of zebrafish. Both the number of bacteria colony forming units and bacteria growth obtained from skin mucus were lower in all concentrations tested (25, 50 and 100 ug nAg/L). Besides, AgNP exposure caused a significant decrease in bacteria growth in zebrafish exposed to 100 ug nAg/L. AgNP accumulated in zebrafish gills at both highest concentrations tested, but this accumulation did not appear to result in oxidative stress. Overall the results indicated toxicological effects of AgNP on bacteria communities living at the zebrafish mucus surface. Although silver accumulation was verified in gills, no evidence of toxicity in terms of oxidative stress was found. PMID- 27393329 TI - Streptomyces phyllanthi sp. nov., isolated from the stem of Phyllanthus amarus. AB - The novel endophytic actinomycete strain PA1-07T was isolated from the stem of Phyllanthus amarus. The strain displayed the consistent characteristics of members of the genus Streptomyces. The strain produced short spiral spore chains on aerial mycelia. It grew at pH 5-9, at 40 degrees C and with a maximum of 5 % (w/v) NaCl. It contained ll-diaminopimelic acid, glucose and ribose in the whole cell hydrolysate. The major cellular menaquinones were MK-9(H4), MK-9(H6) and MK 9(H8), while the major cellular fatty acids were C16 : 0, iso-C14 : 0, iso-C16 : 0 and anteiso-C15 : 0. The polar lipids were composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside and four unknown lipids. The DNA G+C content of the strain was 71 mol%. The strain showed the highest 16S rRNA gene sequence similarity with Streptomyces curacoi JCM 4219T (98.77 %). The DNA-DNA relatedness values between strain PA1-07T and S. curacoi JCM 4219T were lower than 70 %, the cut-off level for assigning strains to the same species. On the basis of these phenotypic and genotypic characteristics, the strain could be distinguished from closely related species of the genus Streptomyces and thus represents a novel species of the genus Streptomyces, for which the name Streptomyces phyllanthi sp. nov. is proposed. The type strain is PA1-07T (=JCM 30865T=KCTC 39785T=TISTR 2346T). PMID- 27393330 TI - Erratum to: Olmutinib: First Global Approval. PMID- 27393331 TI - Pitfalls in the assessment of smoking status detected in a cohort of South African RA patients. AB - This study was conceived in an attempt to explain the unexpectedly high frequency of elevated levels of serum cotinine measured retrospectively in a cohort of predominantly black South African females with rheumatoid arthritis (RA), findings that were inconsistent with the smoking histories derived from health questionnaires. The discrepant findings suggested either a greater tendency towards underreporting of smoking status in the study cohort, or possible confounding effects of the use of smokeless tobacco products. In addition to the cohort of RA patients (n = 138, of whom 115 (83 %) were female), blood samples were also taken from a second cohort consisting of 29 declared smokers, 18 (62 %) of whom where females, 29 smokeless tobacco (SLT) users (all female), and 22 non users of any tobacco products, 18 (82 %) of whom were females. Serum cotinine levels were determined using an ELISA procedure. Cotinine levels of >10.0 ng/ml were detected in serum specimens from 43 (31 %), RA patients of whom 35 (81 %) were female, with a median value of 50.1 ng/ml and interquartile range (iqr) of 68.6. Only 18 of the 35 females indicated that they smoked. The groups of declared smokers and SLT users had equivalent median serum cotinine levels of 88.0 ng/ml (iqr = 10.8 ng/ml) and 87.0 ng/ml (iqr = 15.6 ng/ml), respectively, while cotinine was undetectable in specimens from non-tobacco product users (<0.2 ng/ml). Users of SLT products in South Africa are predominantly female and have serum cotinine levels which are comparable with those of current smokers, raising concerns about the validity of measurement of cotinine as the sole objective marker of smoking status in populations with high usage of SLTs. This situation can be rectified by ensuring that usage of SLT products is accurately recorded in health questionnaires, while inclusion of measurement of one or more additional, objective biomarkers of smoking in combination with cotinine may enable reliable distinction between smoking and usage of SLTs which, given the associated risks, is a strategy of particular relevance in RA. PMID- 27393332 TI - Association between endothelial function and micro-vascular remodeling measured by synchrotron radiation pulmonary micro-angiography in pulmonary arterial hypertension. AB - OBJECTIVES: Pulmonary arterial hypertension (PAH) is a progressive disease which causes increased vascular resistance. In this study, our purpose was to quantify the micro-vascular remodeling in monocrotaline-induced PAH rats using synchrotron radiation pulmonary micro-angiography (SRPA), a method we have previously established in an in vivo rat model. To determine the relationship between endothelial function and vascular remodeling, the local expression of endothelin 1 (ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) was evaluated using immunohistochemical staining. METHODS: Monocrotaline-induced PAH rats were created by subcutaneous injection of monocrotaline. After 2 weeks, SRPA was performed at the Photon Factory of the High Energy Accelerator Research Organization. The internal diameters of pulmonary arterioles were measured using SRPA images. Semi-quantified analyses of ET-1, eNOS and VEGF expression in pulmonary arterioles were performed by immunohistochemical staining. RESULTS: Micro-vascular density and the internal diameters of pulmonary arterioles were significantly decreased in PAH. ET-1 expression was significantly increased in PAH compared with the control (1.53 +/- 0.45 vs. 0.80 +/- 0.14) and eNOS expression was significantly decreased in PAH compared with the control (1.12 +/- 0.59 vs. 1.91 +/- 0.66), although VEGF expression did not differ between the groups. CONCLUSIONS: SRPA can be effectively used for visualizing the decreased pulmonary micro-vasculature associated with PAH. Increased ET-1 expression and decreased eNOS expression may contribute to the proliferation and vasospasm of pulmonary arterioles induced by endothelial dysfunction due to PAH. This SRPA technology may help to identify a correlation between endothelial function and micro-vasculature remodeling in PAH. PMID- 27393333 TI - Evaluation of 60 cases of systemic-pulmonary shunt with cardiopulmonary bypass. AB - OBJECTIVE: In recent years, the median sternotomy approach with cardiopulmonary bypass has been increasingly chosen when systemic-pulmonary shunt surgery is performed as initial palliation for congenital heart diseases with decreased pulmonary blood flow to secure a stable surgical field and to maintain a stable circulation and oxygen supply. Since 2007, this strategy has been applied in our institute. This time, we examine the advantage and disadvantage of this procedure by evaluating the intraoperative and postoperative courses. METHODS: The study investigated 60 cases that underwent systemic-pulmonary shunt surgery under cardiopulmonary bypass at our facility after August 2007. Original diagnosis, age and body weight at surgery, shunt procedure, concomitant procedure, and surgical times were evaluated. The postoperative course of each case and the results of subsequent surgeries were also examined. RESULTS: No death or severe complication occurred during surgery or in the perioperative period. The age at surgery was 4 days-12 years (median 5.1 months), and the body weight was 2.3-28.1 (median 4.7) kg. Surgical procedures were as follows: right modified Blalock-Taussig shunt (mBTS): 35, left mBTS: 11, and central shunt: 14. In addition, the following simultaneous surgeries were conducted: pulmonary artery plasty: 11, unifocalization: 5, main pulmonary artery ligation: 2, interatrial communication enlargement: 4, and total anomalous pulmonary venous drainage repair: 2. CONCLUSION: The outcomes at our facility have validated the safety of systemic pulmonary shunt surgeries under cardiopulmonary bypass, and even the disadvantages of concern were believed to be within acceptable limits. Further innovation and examination are important in pursuit of even less invasive surgeries. PMID- 27393334 TI - Rapid Weight Gain in Pediatric Refugees after US Immigration. AB - Prior studies of immigrants to the United States show significant weight gain after 10 years of US residence. Pediatric refugees are a vulnerable population whose post-immigration weight trajectory has not been studied. We examined the longitudinal weight trajectory of 1067 pediatric refugees seen in a single university based refugee health program between the dates of September 3, 2012 and September 3, 2014 to determine how quickly significant weight gain occurs post-arrival. The most recent BMI was abstracted from the electronic health record and charts reviewed to obtain serial BMI measurements in 3 year increments after the date of US arrival. The mean arrival BMI percentile for all refugees was 47th percentile. This increased significantly to the 63rd percentile within 3 years of US arrival (p < 0.01). This rapid increase was largely attributable to African and South and Southeast Asian refugees. The overall prevalence of age and sex adjusted obesity rose from 7.4 % at arrival to 18.3 % within 9 years of US immigration exceeding the pediatric US national obesity prevalence of 16.9 %. Pediatric refugees are at increased risk of rapid weight gain after US immigration. Targeted interventions focused on prevention of weight gain in specific populations are warranted. PMID- 27393335 TI - Country of Birth and Variations in Asthma and Wheezing Prevalence, and Emergency Department Utilization in Children: A NHANES Study. AB - Asthma prevalence and asthma-related healthcare utilization differ across racial/ethnic groups and geographical areas. This study builds on previous research to examine the relationship between country of birth and asthma prevalence and healthcare utilization using a national data set. The National Health and Nutrition Examination Survey (NHANES) Demographic and Questionnaire Files from 2007 to 2012 were used for this study. We used SPSS complex sampling design to estimate the association between country of birth and asthma prevalence, wheezing and emergency department (ED) use. The sample size was 8272 children and adolescents between the ages of 5 and 19 years old. US-born children had more reported episodes of wheezing (p = 0.024) 95 % CI 1.06; 2.54. There was no association between country of birth and asthma and ED use. US-born children and adolescents compared to foreign-born children and adolescents are more likely to have episodes of wheezing. PMID- 27393336 TI - HIV Knowledge Among Pregnant Latinas in Rural South Carolina. AB - To inform and strengthen culturally-tailored HIV perinatal prevention, we assessed HIV knowledge among pregnant Latinas receiving prenatal care in rural South Carolina. We administered an 11 item HIV knowledge scale (n = 171). Women who answered 8 of 11 (73 %) items correctly were categorized as having "high" knowledge; <8 items correct was categorized as "low" knowledge. Seventy-six percent of participants had low HIV knowledge; only 37 % knew that there is medicine to prevent mother-to-child HIV transmission. In multivariate analyses, high HIV knowledge was more likely among women who had >=high school education compared with women with elementary school education only (Adjusted Odds Ratio 10.5, 95 % Confidence Interval 3.3-33.6). These findings highlight the need for targeted educational interventions to better inform Latinas regarding perinatal HIV prevention and transmission risks. Enhancing efforts with patients and providers is aligned with national goals for HIV prevention and elimination of perinatal transmission. PMID- 27393337 TI - Endogenous cardiac steroids in animal models of mania. AB - OBJECTIVES: Bipolar disorder (BD) is a complex psychiatric disorder characterized by mania and depression. Alterations in brain Na(+) , K(+) -ATPase and cardiac steroids (CSs) have been detected in BD, raising the hypothesis of their involvement in this pathology. The present study investigated the behavioral and biochemical consequences of a reduction in endogenous brain CS activity in animal models of mania. METHODS: Amphetamine (AMPH)-induced hyperactivity in BALB/c and black Swiss mice served as a model of mania. Behavior was evaluated in the open field test in naive mice or in mice treated with anti-ouabain antibodies. CS levels were determined by enzyme-linked immunosorbent assay (ELISA), using sensitive and specific anti-ouabain antibodies. Extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) phosphorylation levels in the frontal cortex were determined by western blot analysis. RESULTS: Administration of AMPH to BALB/c and black Swiss mice resulted in a marked increase in locomotor activity, accompanied by a threefold increase in brain CSs. The lowering of brain CSs by the administration of anti-ouabain antibodies prevented the hyperactivity and the increase in brain CS levels. AMPH caused an increase in phosphorylated ERK (p-ERK) and phosphorylated Akt (p-Akt) levels in the frontal cortex, which was significantly reduced by administration of the antibodies. A synthetic 'functional antagonist' of CSs, 4-(3'alpha-15'beta-dihydroxy-5'beta-estran 17'beta-yl) furan-2-methyl alcohol, also resulted in attenuation of AMPH-induced hyperactivity. CONCLUSIONS: These results are in accordance with the notion that malfunctioning of the Na(+) , K(+) -ATPase/CS system may be involved in the manifestation of mania and identify this system as a potential new target for drug development. PMID- 27393338 TI - The next generation of target capture technologies - large DNA fragment enrichment and sequencing determines regional genomic variation of high complexity. AB - BACKGROUND: The ability to capture and sequence large contiguous DNA fragments represents a significant advancement towards the comprehensive characterization of complex genomic regions. While emerging sequencing platforms are capable of producing several kilobases-long reads, the fragment sizes generated by current DNA target enrichment technologies remain a limiting factor, producing DNA fragments generally shorter than 1 kbp. The DNA enrichment methodology described herein, Region-Specific Extraction (RSE), produces DNA segments in excess of 20 kbp in length. Coupling this enrichment method to appropriate sequencing platforms will significantly enhance the ability to generate complete and accurate sequence characterization of any genomic region without the need for reference-based assembly. RESULTS: RSE is a long-range DNA target capture methodology that relies on the specific hybridization of short (20-25 base) oligonucleotide primers to selected sequence motifs within the DNA target region. These capture primers are then enzymatically extended on the 3'-end, incorporating biotinylated nucleotides into the DNA. Streptavidin-coated beads are subsequently used to pull-down the original, long DNA template molecules via the newly synthesized, biotinylated DNA that is bound to them. We demonstrate the accuracy, simplicity and utility of the RSE method by capturing and sequencing a 4 Mbp stretch of the major histocompatibility complex (MHC). Our results show an average depth of coverage of 164X for the entire MHC. This depth of coverage contributes significantly to a 99.94 % total coverage of the targeted region and to an accuracy that is over 99.99 %. CONCLUSIONS: RSE represents a cost-effective target enrichment method capable of producing sequencing templates in excess of 20 kbp in length. The utility of our method has been proven to generate superior coverage across the MHC as compared to other commercially available methodologies, with the added advantage of producing longer sequencing templates amenable to DNA sequencing on recently developed platforms. Although our demonstration of the method does not utilize these DNA sequencing platforms directly, our results indicate that the capture of long DNA fragments produce superior coverage of the targeted region. PMID- 27393339 TI - Circulating microRNAs as biomarkers for rituximab therapy, in neuromyelitis optica (NMO). AB - BACKGROUND: Neuromyelitis optica (NMO) is a chronic autoimmune disease of the central nervous system (CNS). The main immunological feature of the disease is the presence of autoantibodies to Aquaporin 4 (AQP4+), identified in about 82 % of cases. Currently, there are no reliable biomarkers for monitoring treatment response in patients with NMO. In an effort to identify biomarkers, we analyzed microRNAs (miRNAs) in the blood of rituximab-treated NMO patients before and after therapy. METHODS: Total RNA extracted from whole blood of nine rituximab responsive NMO patients before and 6 months following treatment was subjected to small RNAseq analysis. The study included an additional group of seven untreated AQP4+ seropositive NMO patients and 15 healthy controls (HCs). RESULTS: Fourteen miRNAs were up regulated and 32 were downregulated significantly in the blood of NMO patients following effective therapy with rituximab (all p < 0.05). Furthermore, we show that expression of 17 miRNAs was significantly higher and of 25 miRNAs was significantly lower in untreated NMO patients compared with HCs (all p < 0.05). Following rituximab treatment, the expression levels of 10 of the 17 miRNAs that show increased expression in NMO reverted to the levels seen in HCs. Six of these "normalized" miRNAs are known as brain-specific/enriched miRNAs. CONCLUSIONS: Specific miRNA signatures in whole blood of patients with NMO might serve as biomarkers for therapy response. Furthermore, monitoring the levels of brain-specific/enriched miRNAs in the blood might reflect the degree of disease activity in the CNS of inflammatory demyelinating disorders. PMID- 27393341 TI - Formulation and in vitro evaluation of polymeric enteric nanoparticles as dermal carriers with pH-dependent targeting potential. AB - pH-sensitive nanoparticles which release in a controlled fashion on the skin or dissolve in the hair follicle could significantly improve treatment effectiveness and make transfollicular drug delivery a success. Dexamethasone-loaded Eudragit(r) L 100 nanoparticles were prepared by nanoprecipitation from an organic drug-polymer solution. Their toxicity potential was assessed using isolated human fibroblasts. pH-dependent swelling and erosion kinetics of the nanoparticles were investigated by dynamic light scattering and viscosity measurements and its effect on drug release was assessed in vitro with Franz diffusion cells. Stable, 100-550nm-sized dexamethasone-loaded Eudragit(r) L 100 nanoparticles with drug loading capacity and entrapment efficiency as high as 8.3% and 85%, respectively, were obtained by using polyvinyl alcohol as a stabilizer and ethanol as organic solvent. The nanoparticles showed little or no toxicity on isolated normal human fibroblasts. Dexamethasone existed in the nanoparticles as solid solution or in amorphous form. The nanoparticles underwent extensive swelling and slow drug release in media with a low buffer capacity (as low as 10mM) and a higher pH or at a pH close to the dissolution pH of the polymer (pH6) and a higher buffer capacity. In 40mM buffer and above pH6.8, the nanoparticles eroded fast or dissolved completely and thus released the drug rapidly. pH-sensitive nanoparticles which potentially release in a controlled manner on the stratum corneum but dissolve in the hair follicle could be prepared. PMID- 27393340 TI - Nitric Oxide Regulates Skeletal Muscle Fatigue, Fiber Type, Microtubule Organization, and Mitochondrial ATP Synthesis Efficiency Through cGMP-Dependent Mechanisms. AB - AIM: Skeletal muscle nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSMU and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. RESULTS: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSMU and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1-/- muscle. Functional analyses of GC1-/- muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA-IIX fiber balance. Force deficits in GC1-/- muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. INNOVATION: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. CONCLUSIONS: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency. Antioxid. Redox Signal. 26, 966-985. PMID- 27393342 TI - Pharmacokinetic considerations of nanodelivery to the brain: Using modeling and simulations to predict the outcome of liposomal formulations. AB - The use of nanocarriers is an intriguing solution to increase the brain delivery of novel therapeutics. The aim of this paper was to use pharmacokinetic analysis and simulations to identify key factors that determine the effective drug concentration-time profile at the target site in the brain. Model building and simulations were based on experimental data obtained from the administration of the opioid peptide DAMGO in glutathione tagged PEGylated liposomes to rats. Different pharmacokinetic models were investigated to explore the mechanisms of increased brain delivery. Concentration-time profiles for a set of formulations with varying compound and carrier characteristics were simulated. By controlling the release rate from the liposome, the time profile and the extent of brain delivery can be regulated. The modeling did not support a mechanism of the liposomes passing the brain endothelial cell membrane in an intact form through endocytosis or transcytosis. The most likely process was found to be fusion of the liposome with the endothelial luminal membrane. The simulations revealed that low permeable compounds, independent on efflux, will gain the most from a nanocarrier formulation. The present model based approach is useful to explore and predict possibilities and limitations of carrier-based systems to the brain. PMID- 27393343 TI - Selection on metabolic pathway function in the presence of mutation-selection drift balance leads to rate-limiting steps that are not evolutionarily stable. AB - BACKGROUND: While commonly assumed in the biochemistry community that the control of metabolic pathways is thought to be critical to cellular function, it is unclear if metabolic pathways generally have evolutionarily stable rate limiting (flux controlling) steps. RESULTS: A set of evolutionary simulations using a kinetic model of a metabolic pathway was performed under different conditions to evaluate the evolutionary stability of rate limiting steps. Simulations used combinations of selection for steady state flux, selection against the cost of molecular biosynthesis, and selection against the accumulation of high concentrations of a deleterious intermediate. Two mutational regimes were used, one with mutations that on average were neutral to molecular phenotype and a second with a preponderance of activity-destroying mutations. The evolutionary stability of rate limiting steps was low in all simulations with non-neutral mutational processes. Clustering of parameter co-evolution showed divergent inter molecular evolutionary patterns under different evolutionary regimes. CONCLUSIONS: This study provides a null model for pathway evolution when compensatory processes dominate with potential applications to predicting pathway functional change. This result also suggests a possible mechanism in which studies in statistical genetics that aim to associate a genotype to a phenotype assuming independent action of variants may be mis-specified through a mis characterization of the link between individual gene function and pathway function. A better understanding of the genotype-phenotype map has potential applications in differentiating between compensatory changes and directional selection on pathways as well as detecting SNPs and fixed differences that might have phenotypic effects. REVIEWERS: This article was reviewed by Arne Elofsson, David Ardell, and Shamil Sunyaev. PMID- 27393344 TI - Habitat degradation disrupts neophobia in juvenile coral reef fish. AB - Habitat degradation not only disrupts habitat-forming species, but alters the sensory landscape within which most species must balance behavioural activities against predation risk. Rapidly developing a cautious behavioural phenotype, a condition known as neophobia, is advantageous when entering a novel risky habitat. Many aquatic organisms rely on damage-released conspecific cues (i.e. alarm cues) as an indicator of impending danger and use them to assess general risk and develop neophobia. This study tested whether settlement-stage damselfish associated with degraded coral reef habitats were able to use alarm cues as an indicator of risk and, in turn, develop a neophobic response at the end of their larval phase. Our results indicate that fish in live coral habitats that were exposed to alarm cues developed neophobia, and, in situ, were found to be more cautious, more closely associated with their coral shelters and survived four times better than non-neophobic control fish. In contrast, fish that settled onto degraded coral habitats did not exhibit neophobia and consequently suffered much greater mortality on the reef, regardless of their history of exposure to alarm cues. Our results show that habitat degradation alters the efficacy of alarm cues with phenotypic and survival consequences for newly settled recruits. PMID- 27393345 TI - Genome-wide assessment of Parkinson's disease in a Southern Spanish population. AB - Here, we set out to study the genetic architecture of Parkinson's disease (PD) through a Genome-Wide Association Study in a Southern Spanish population. About 240 PD cases and 192 controls were genotyped on the NeuroX array. We estimated genetic variation associated with PD risk and age at onset (AAO). Risk profile analyses for PD and AAO were performed using a weighted genetic risk score. Total heritability was estimated by genome-wide complex trait analysis. Rare variants were screened with single-variant and burden tests. We also screened for variation in known PD genes. Finally, we explored runs of homozygosity and structural genomic variations. We replicate PD association (uncorrected p-value < 0.05) at the following loci: ACMSD/TMEM163, MAPT, STK39, MIR4697, and SREBF/RAI1. Subjects in the highest genetic risk score quintile showed significantly increased risk of PD versus the lowest quintile (odds ratio = 3.6, p-value < 4e( 7)), but no significant difference in AAO. We found evidence of runs of homozygosity in 2 PD-associated regions: one intersecting the HLA-DQB1 gene in 6 patients and 1 control; and another intersecting the GBA-SYT11 gene in PD case. The GBA N370S and the LRRK2 G2019S variants were found in 8 and 7 cases, respectively, replicating previous work. A structural variant was found in 1 case in the PARK2 gene locus. This current work represents a comprehensive assessment at a genome-wide level characterizing a novel population in PD genetics. PMID- 27393346 TI - Carrier screening for beta-thalassemia in the Maldives: perceptions of parents of affected children who did not take part in screening and its consequences. AB - The Republic of Maldives (Maldives) is an island nation in the Indian Ocean with a population of 344, 023. Studies show that Maldives has one of the world's highest thalassemia carrier rates. It is estimated that 16-18 % of the Maldivians are beta-thalassemia carriers, and approximately 28 new beta-thal cases are recorded annually. Poor uptake of screening for the condition is one of the main reasons for this high number of new cases. The aim of this study was to explore the reasons for not testing for thalassemia in Maldives before or after marriage. Findings show that participants did not undergo carrier tests because of poor awareness and not fully knowing the devastating consequences of the condition. The outcomes of not testing were distressing for most participants. Religion played a vital role in all the decisions made by the participants before and after the birth of a beta-thal child. PMID- 27393347 TI - Integrative analysis of diffusion-weighted MRI and genomic data to inform treatment of glioblastoma. AB - Gene expression profiling from glioblastoma (GBM) patients enables characterization of cancer into subtypes that can be predictive of response to therapy. An integrative analysis of imaging and gene expression data can potentially be used to obtain novel biomarkers that are closely associated with the genetic subtype and gene signatures and thus provide a noninvasive approach to stratify GBM patients. In this retrospective study, we analyzed the expression of 12,042 genes for 558 patients from The Cancer Genome Atlas (TCGA). Among these patients, 50 patients had magnetic resonance imaging (MRI) studies including diffusion weighted (DW) MRI in The Cancer Imaging Archive (TCIA). We identified the contrast enhancing region of the tumors using the pre- and post-contrast T1 weighted MRI images and computed the apparent diffusion coefficient (ADC) histograms from the DW-MRI images. Using the gene expression data, we classified patients into four molecular subtypes, determined the number and composition of genes modules using the gap statistic, and computed gene signature scores. We used logistic regression to find significant predictors of GBM subtypes. We compared the predictors for different subtypes using Mann-Whitney U tests. We assessed detection power using area under the receiver operating characteristic (ROC) analysis. We computed Spearman correlations to determine the associations between ADC and each of the gene signatures. We performed gene enrichment analysis using Ingenuity Pathway Analysis (IPA). We adjusted all p values using the Benjamini and Hochberg method. The mean ADC was a significant predictor for the neural subtype. Neural tumors had a significantly lower mean ADC compared to non-neural tumors ([Formula: see text]), with mean ADC of [Formula: see text] and [Formula: see text] for neural and non-neural tumors, respectively. Mean ADC showed an area under the ROC of 0.75 for detecting neural tumors. We found eight gene modules in the GBM cohort. The mean ADC was significantly correlated with the gene signature related with dendritic cell maturation ([Formula: see text], [Formula: see text]). Mean ADC could be used as a biomarker of a gene signature associated with dendritic cell maturation and to assist in identifying patients with neural GBMs, known to be resistant to aggressive standard of care. PMID- 27393348 TI - Ferumoxytol-enhanced MRI differentiation of meningioma from dural metastases: a pilot study with immunohistochemical observations. AB - Malignant dural neoplasms are not reliably distinguished from benign dural neoplasms with contrast-enhanced magnetic resonance imaging (MRI). MRI enhancement in central nervous system (CNS) diseases imaged with ferumoxytol has been attributed to intracellular uptake in macrophages rather than vascular leakage. We compared imaging to histopathology and immunohistochemistry in meningiomas and dural metastases having ferumoxytol-enhanced MRI (FeMRI) and gadolinium-enhanced MRI (GdMRI) in order to correlate enhancement patterns to macrophage presence and vascular state. All patients having extraaxial CNS tumors were retrospectively selected from one of two ongoing FeMRI studies. Enhancement was compared between GdMRI and FeMRI. Diagnoses were confirmed histologically and/or by characteristic imaging. Tumor and vascular histology was reviewed. Immunohistochemical staining for CD68 (a macrophage marker), Connexin-43 (Cx43) (a marker of normal gap junctions), and smooth muscle actin (SMA) as a marker of vascularity, was performed in seven study cases with available tissue. Immunohistochemistry was performed on archival material from 33 subjects outside of the current study as controls: 20 WHO grade I cases of meningioma and 13 metastatic tumors. Metastases displayed marked delayed enhancement on FeMRI, similar to GdMRI. Four patients with dural metastases and one patient with meningioma showed similar enhancement on FeMRI and GdMRI. Five meningiomas with typical enhancement on GdMRI lacked enhancement on FeMRI. Enhancement on FeMRI was better associated with decreased Cx43 expression than intralesional macrophages. These pilot data suggest that FeMRI may better differentiate metastatic disease from meningiomas than GdMRI, and that differences in tumor vasculature rather than macrophage presence could underlie differences in contrast enhancement. PMID- 27393349 TI - Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with gammadeltaT cells in human glioblastoma in vitro and in vivo. AB - Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and gammadeltaT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG. Apoptosis inhibition assays were also conducted. In vivo xenograft assays were performed in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Sug)/Jic mice subcutaneously implanted with U87MG and U138MG cells. Growth inhibition and apoptosis detection assays demonstrated that MDA inhibited GBM cell growth via apoptosis, which was markedly enhanced by ex vivo expanded GDT. A pan-caspase inhibitor, z-VAD-fmk, inhibited MDA-induced U138MG apoptosis and MDA/GDT-induced U87MG and U138MG apoptosis. But z-VAD-fmk increased MDA-induced U87MG apoptosis. MDA/GDT-mediated apoptosis was blocked by the anti-T cell receptor (TCR) Vgamma9, mevalonate pathway inhibitor, granzyme B inhibitor, and antitumor necrosis factor (TNF)-alpha. In vivo xenograft assays showed that combined intraperitoneal administration of MDA/GDT induced antitumor effects on unestablished U87MG-derived subcutaneous tumors. MDA exerted direct and GDT-mediated anti-GBM apoptotic effects in a caspase-dependent manner. GDT recognized MDA-exposed GBM cells via TCRVgamma9 and induced apoptosis via granzyme B and TNF-alpha release. Because MDA elicited anti-GBM effects in synergy with GDT in vivo, a combination of MDA and ex vivo-generated GDT could be an effective treatment in patients with GBM. PMID- 27393352 TI - Purification and Some Properties of p-Nitrophenyl-beta-D-glucoside-hydrolyzing Enzymes in Culture Filtrate of Bacillus circulans KA-304 Grown on Cell-wall Preparation of Schizophyllum commune. AB - Hydrolyzing activities toward p-nitrophenyl (p-NP)-beta-D-glucoside and laminarin in a culture filtrate of Bacillus circulans KA-304, which has been observed to form protoplasts from Schizophyllum commune mycelia, increased when the bacterium was grown on a cell-wall preparation (CWP) of S. commune or laminarin as a carbon source. An analysis of the filtrate with the CWP suggested occurrence of two major p-NP-beta-D-glucoside-hydrolyzing enzymes (beta-D-glucosidases I and II) and a laminarin-hydrolyzing enzyme. After separation by DEAE-cellulose column chromatography, beta-D-glucosidases I and II were isolated (beta-D-glucosidase I: 13-fold purification with 34% yield; beta-D-glucosidase II: 26-fold with 8%). The enzymes resembled each other in their properties except for their molecular weight, subunit structure (beta-D-glucosidase I: 200,000, tetramer; II: 100,000, dimer), and susceptibility to such substances as p-chloromercuribenzoic acid and Ag(+) ion. beta-D-Glucosidases I and II hydrolyzed gentiobiose (beta-1,6 glucosidic linkage; Km=3.6 mM, beta-D-glucosidase I; 4.6 mM, beta-D-glucosidase II) and laminaribiose (beta-1,3 glucosidic linkage; Km=6.1 mM, beta-D-glucosidase I; 6.7 mD beta-D-glucosidase II), and showed a certain reactivity toward laminarin as well. PMID- 27393350 TI - The effects of sequential treatments on hippocampal volumes in malignant glioma patients. AB - Malignant gliomas (MG) are very aggressive tumors. In an effort to improve the outcome, the patients receive multi-modal therapies such as surgery, radiation and chemotherapy (temozolomide followed in many cases by bevacizumab). The survivors are affected by multiple learning and memory deficits. Greater deterioration over time in hippocampal specific cognitive tasks was shown in patients receiving bevacizumab in addition to radiation and temozolomide for a longer period of time (RTOG 0825). The rate of hippocampal atrophy in patients treated with radiation and temozolomide followed by bevacizumab is not yet determined, and is the goal of the present study. We used the serial MRIs obtained as parts of standard clinical care in patients with MG. Measurements were done using the Medical Image Processing, Analysis and Visualization (MIPAV) software. The hippocampus in the contralateral hemisphere was manually traced and measured, to avoid morphological structure changes induced by the tumor, radiation fields or surgical markers. We determined a longitudinal progression of hippocampal atrophy-with the maximum volume loss (33.26 %) for the patients that were on treatment for 5 years. There was no detectable hippocampal atrophy during the chemo-radiation followed by adjuvant temozolomide. A significant decrease in the absolute hippocampus volume was noted after 6 months of continuous bevacizumab treatment (p < 0.05). The hippocampal volume loss progressed over the next 3 years, and was higher than the one previously reported in Alzheimer disease patients. The hippocampal volume loss is minimal during the 1 month after diagnosis, when the patients receive chemo-radiation and adjuvant temozolomide. However, prolonged treatment including bevacizumab is associated with a significant rate of hippocampal volume loss. PMID- 27393353 TI - Role of Sucrose in Gamma-irradiated Chrysanthemum Cut Flowers. AB - Vase solution containing 2% sucrose prevented the deterioration of chrysanthemum (Dendranthema grandiflorum Kitamura) cut flowers induced by gamma-rays at 750 Gy. Glucose, fructose, and sucrose in florets and leaves of irradiated chrysanthemums decreased more rapidly than those of unirradiated ones, when the cut chrysanthemums were held in a vase solution without sucrose. The sugar contents of florets and leaves and the respiratory rate of irradiated chrysanthemums held with sucrose remained at higher levels than those of unirradiated ones. Incorporation of (14)C from [(14)C]sucrose into CO2 was increased by irradiation. Incorporation of [alpha-(32)P]dTTP into trichloroacetic acid (TCA) insoluble substances in florets was increased by irradiation and by exogenous sucrose supply. These results suggest that sucrose in a vase solution was used as a respiratory substrate and facilitated the repair of radiation-induced damage, resulting in the extension of longevity of irradiated chrysanthemums. PMID- 27393354 TI - Distribution of Defense-Related Enzymatic Activities in the Quiescent Organs of Phaseolus vulgaris L. Seeds. AB - Analysis of quiescent seed extracts of Phaseolus vulgaris cultivars found high activities of chitinase, N,N'-diacetylchitobiase and beta-N-acetylhexosaminidase in whole seeds and their dissected organs (cotyledons, axis, and seed coat). Activities of these enzymes were compared in seeds of two cultivars phenotypically distinguishable by soft white (cv. Surattowonder) and hard brown (cv. Maisugata) seed coats. In both cultivars, chitinase activity was found high in all organs, chitobiase in the seed coat, and beta-N-acetylhexosaminidase mainly in the axis. In terms of specific activity, all three enzymes were extraordinarily higher in extracts of seed coat than the others, specially referring to the cultivar Surattowonder. Although the cultivars showed in general similar distribution patterns of activities among their seed organs, the discrepancies found between them seem to be expressing intrinsic attributes of their seed coats. The relationship between the two cultivars, the enzyme activities measured and defense mechanisms are discussed. PMID- 27393351 TI - Reproducibility of macromolecule suppressed GABA measurement using motion and shim navigated MEGA-SPECIAL with LCModel, jMRUI and GANNET. AB - OBJECTIVE: Measuring the pure form of GABA has become increasingly important because of its association with behaviour and certain pathologies. The aim of this study was to assess the reproducibility of GABA measurements using a shim and motion navigated MEGA-SPECIAL sequence with LCModel, jMRUI and GANNET software. MATERIALS AND METHODS: Motion and shim navigated MEGA-SPECIAL scans were acquired in 20 healthy subjects. Two acquisitions were performed for each of two regions: the anterior cingulate (ACC) and medial-parietal (PAR) cortices. Absolute GABA concentration ([Formula: see text]) and GABA-to-Creatine ratio (GABA/Cr) were quantified using the three software packages. RESULTS: Using the within-subject coefficient of variation (CVws) as an index, reproducibility for both GABAH20 and GABA/Cr ranged from 13 to 22 % in the ACC and 13 to 18 % in PAR using the three software packages. CONCLUSION: Based on CVws, GABA concentrations in both the ACC and PAR are reproducible using a shim and motion navigated MEGA SPECIAL sequence with any of the three software packages, thus demonstrating the ability to quantify the pure form of GABA using these software in studies relating GABA to pathology and healthy behaviour. PMID- 27393355 TI - Synthesis of Some 1-Methyladenine Analogs and Their Biological Activities on Starfish Oocyte Maturation. AB - Starfish oocytes are naturally arrested at the prophase stage of the first meiotic division and resume meiosis in response to the maturation-inducing hormone 1-methyladenine. Five analogs of 1-methyladenine including three novel ones were synthesized and tested for biological activities as 1-methyladenine agonists or antagonists in triggering reinitiation of meiosis of starfish Asterina pectinifera oocytes, as well as for competition in binding to putative 1 methyladenine receptors with respect to 1-methyladenine. 1-Ethyladenine was an effective agonist, but 1-propyladenine served as a weak antagonist to 1 methyladenine, indicating strict specificity for a relatively small N-1 substituent. Analogs in which carboxymethyl or methyl group substitutes for a hydrogen of 6-amino group still retained oocyte maturation-inducing activity, but to a much lesser degree. The results of the competitive binding assay with cortices of oocytes demonstrated that these agonists or antagonist inhibited the binding of [(3)H]1-methyladenine to receptors. 8-methylamino-1-methyladenine competed only weakly with [(3)H]1-methyladenine for the binding to cortices, although it behaved as a potent antagonist. PMID- 27393356 TI - The Relationship between Transport-enhancement Effects and Cell Viability by Capric Acid Sodium Salt, Monocaprin, and Dicaproin. AB - Using Caco-2 cell monolayers and MTT assay, the relationship between cell viability (a) and transport-enhancement effect of 1,2-dicaproin (C6DG), monocaprin (C10MG), and capric acid sodium salt (C10FANa) was examined. Transport enhancement effect was assessed by apparent permeability (P app) of penicillin V. There was a linear relationship between (P app-aS a) and (1-a) values, where S a was the apparent permeability for the viable cells. The apparent permeability for the damaged cells (S d) was evaluated from the slope of the line. Each of the enhancer compounds gave a different S d value 2.00*10(-4), 0.82*10(-4), and 0.10*10(-4) cm/s for C6DG, C10MG, and C10FANa, respectively, but the value was independent of its concentration for C10MG and C10FANa. C6DG would be the safest enhancer among the three compounds because of its high S d value at the low level of cell damage. S d could be used as a criterion for estimating the safety of enhancers. PMID- 27393357 TI - Phenylphenalenone-type Phytoalexins from Unripe Bungulan Banana Fruit. AB - Fourteen phenylphenalenone-type phytoalexins (1-14), including three new compounds, were isolated from the peel of unripe Musa acuminata [AAA] cv. Bungulan fruit which had been injured and then inoculated with conidia of Colletotrichum musae. These new phytoalexins were identified as (+)-cis-2,3 dihydro-2,3-dihydroxy-4-(4'-hydroxyphenyl)phenalen-1-one (12), 9-(3',4' dimethoxyphenyl)-2-methoxyphenalen-1-one (13) and 9-(4'-hydroxyphenyl)-2 methoxyphenalen-1-one (14). The ratios of the relative intensities of the [M](+)/[M-H](+) ions or [M-H2O](+)/[M-H2O-H](+) ions in the EI mass spectra were applied to discriminate between 4- and 9-phenylphenalenones. An antifungal test on the phytoalexins showed that a phenolic hydroxyl group was essential for the activity. PMID- 27393358 TI - Near Infra Red Detection of Internally Moldy Nuts. AB - Transmittance near infra red (NIR) spectra (500-1500 nm) of individual peanut was measured to detect the internally moldy nuts. The moldy nuts the appearance of which had little difference from the sound nuts by visual observations could be distinguished from each other by comparing the transmittance ratio of 700 nm to 1100 nm by NIR spectrometry. The fungal hydrolysis of the triglycerides that were contained in the nut seemed to account for these differences on the NIR spectra. Because of the higher incidence of aflatoxin (AF) contamination on these moldy nuts, taking out the internally moldy nuts detected by NIR, could drastically reduce the AF content of the overall lot of peanuts. PMID- 27393359 TI - Potassium Iodide-Induced Changes in Pyruvate Dehydrogenase Complex from Bacillus stearothermophilus. AB - Treatment with KI and its subsequent removal induced disassembly of Bacillus stearothermophilus pyruvate dehydrogenase complex (PDC) and association of disassembly products, respectively. The disassembly yielded neither completely dissociated components nor aggregate, but did yield a few molecular forms smaller than PDC. Depending on the KI concentration, these changes were of three phases: K-1, below 0.6 M; K-2, 1.0-1.5 M; K-3, above 1.8 M. PDC was disassembled in K-1 to C1 comprising pyruvate decarboxylase and lipoate acetyltransferase mainly and C2 comprising the decarboxylase and dihydrolipoamide dehydrogenase. In K-1, the removal of KI resulted in an apparent reconstitution of PDC. The mixing of C1 with an excess of C2 yielded an assembly larger than PDC and restored enzyme activities, but specific activities were different from those of PDC. In K-2 and K-3 phases, complexes smaller than PDC were yielded from disassembly products, and activities except for that of the acetyltransferase were not restored. PMID- 27393360 TI - Effects of Bay m 1099, an alpha-Glucosidase Inhibitor, on Starch Degradation in Germinating Mung Beans. AB - To examine the mechanism of starch degradation in legume cotyledons and the physiological role of alpha-glucosidase, mung bean seeds were germinated in the presence of Bay m 1099, an alpha-glucosidase inhibitor. Bay m 1099 (10 MUg/ml medium), which minimized the growth deterioration of the mung bean seedlings, caused no changes in the overall rate of starch degradation and of soluble carbohydrate production in the cotyledons, although alpha-glucosidase activity had been completely suppressed. Total amylase and phosphorylase activities were not influenced by Bay m 1099. These results suggest that the mung bean alpha glucosidase is less responsible for starch degradation, unlike wheat alpha glucosidase [Konishi et al., Biosci. Biotech. Biochem., 58, 135-139 (1994)]. PMID- 27393361 TI - Effect of Antioxidants in Preventing the Thermal Decomposition of Phosphatidylcholine Hydroperoxide. AB - Some typical antioxidants, sesamol, alpha-tocopherol, BHT and ascorbic acid, were examined for their effects on preventing the thermal decomposition of phosphatidylcholine hydroperoxide (PC-OOH), sesamol alone showing some activity. The others, however, had no significant effect, which is in sharp contrast to our previous studies on their remarkable activity toward the thermal decomposition of fatty acid hydroperoxide. Ascorbic acid, which accelerated the decomposition of fatty acid hydroperoxide, was found to have no effect on PC-OOH in its decomposition and prevention. PMID- 27393362 TI - Analysis of Glycerophospholipid Hydroperoxides by Ion Spray Mass Spectrometry. AB - Synthetic phosphatidylcholine hydroperoxide (PC-OOH), phosphatidylethanolamine hydroperoxide (PE-OOH) and phosphatidylglycerol hydroperoxide (PG-OOH) could be analyzed by ion spray ionization mass spectrometry, clearly affording the molecular ion peaks as protonated ion species without any fragmentation. Linearity between PC-OOH concentration and peak intensity, and the minimum detectable concentration of PC-OOH were obtained. PMID- 27393363 TI - Effects of Unsaturated Uronic Acid Residues at Non-reducing End on Bond Cleavage Frequency of Poly(1,4-alpha-L-guluronide) Lyase from Enterobacter cloacae M-1. AB - The mode of action of poly(1,4-alpha-L-guluronide) lyase from Enterobacter cloacae M-1 on unsaturated oligoguluronic acids was studied using fluorophore assisted carbohydrate electrophoresis. The polyguluronate lyase degraded unsaturated penta-, hexa-, and heptaguluronic acids, but not unsaturated oligoguluronic acids with DPs less than 4. On comparison with the aspect of enzymatic degradation of unsaturated oligoguluronic acid and saturated oligoguluronic acid having the same DP, the former was degraded faster than the latter, and also the cleavage pattern of the polyguluronate lyase on unsaturated oligoguluronic acids was considerably different from that on saturated oligoguluronic acids. From the results described above, we suggest that the affinity of the first subsite from the non-reducing end side of the enzyme to Delta residues is lower than that to GulA residues. PMID- 27393364 TI - Effects of Substrate Solubility in Interesterification with Triolein by Immobilized Lipase in Supercritical Carbon Dioxide. AB - The interesterification reaction by immobilized lipase between triolein and behenic acid (BA) or ethyl behenate (EB) was investigated in supercritical carbon dioxide (SCCO2) to produce 1,3-dibehenoyl-2-oleoyl glycerol (BOB). The incorporation rate of behenoyl group to triolein was much higher with EB as a substrate than with BA. The solubility in SCCO2 was found to be significantly higher for EB than BA, which seemed to cause the higher formation rate of the behenoyl-enzyme complex in the former case to give the higher production rate of the final interesterification product, BOB. PMID- 27393365 TI - Pyricuol, a New Phytotoxin from Magnaporthe grisea. AB - A new pyriculol-related phytotoxin, designated as pyricuol (1), was isolated from a liquid culture of Magnaporthe grisea, the causal fungus of rice blast disease, together with two known metabolites, pyriculol (2) and dihydropyriculol. Its structure was determined on the basis of physicochemical and spectroscopic data to be 2-(3-hydroxymethyl-1,4-hexadienyl)-6-hydroxybenzaldehyde. PMID- 27393366 TI - Inhibition of Glucan Synthesis by Casein Polymers Crosslinked by Glutaraldehyde. AB - Glutaraldehyde-crosslinked alpha-casein polymers with molecular masses of 1 5*10(5) were found to inhibit adhesive insoluble glucan formation catalyzed by glucan synthases from Streptococcus sobrinus B13, a cariogenic oral bacterium. Of the three subcomponents of the glucan synthases tested, primer-dependent insoluble glucan synthase was inhibited specifically by the M r~2.7*10(5) polymer at a concentration of 1.4-8.5 MUg/ml. The polymer was also active in inhibiting the artificial plaque formation by S. sobrinus B13. PMID- 27393367 TI - The Characterization of Acetic Acid Bacteria Efficiently Producing Bacterial Cellulose from Sucrose: The Proposal of Acetobacter xylinum subsp. nonacetoxidans subsp. Nov. AB - A taxonomic study was done for the isolates obtained as cellulose high producers from sucrose. These strains were found to have a common characteristic unique for Acetobacter; they did not oxidize acetate and lactate. Therefore, we concluded that these isolates are classified as a new subspecies and proposed Acetobacter xylinum subsp. nonacetoxidans subsp. nov. BPR 2002 (=JCM 10150) was designated as a type strain of the new subspecies. PMID- 27393368 TI - Simple Method for Detecting Glycoproteins Dot-blotted or Electro-blotted on to a Polyvinylidene Difluoride Membrane. AB - A simple method is described for detecting glycoproteins which had been dot blotted or electro-blotted on to a polyvinylidene difluoride (PVDF) membrane after sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. This method is based on the periodate oxidation of glycoproteins on a PVDF membrane with subsequent staining by the chromophoric hydrazide, 4-N,N-dimethylamino-4' azobenzene sulfonyl hydrazide. The glycoproteins could be visualized as red colored spots or bands in the range of 0.16-0.31 MUgamma. PMID- 27393369 TI - Novel Stereoselective Reaction of Levoglucosenone with Furfural. AB - Levoglucosenone reacted with furfural in the presence of an aqueous base to give a product in high yield with high stereoselectivity. The structure, including the stereochemistry of the product, was elucidated by NMR analyses. PMID- 27393370 TI - Behavior, neuropsychology and fMRI. AB - Cognitive neuroscientists in the late 20th century began the task of identifying the part(s) of the brain concerned with normal behavior as manifest in the psychological capacities as affective powers, reasoning, behaving purposively and the pursuit of goals, following introduction of the 'functional magnetic resonance imaging' (fMRI) method for identifying brain activity. For this research program to be successful two questions require satisfactory answers. First, as the fMRI method can currently only be used on stationary subjects, to what extent can neuropsychological tests applicable to such stationary subjects be correlated with normal behavior. Second, to what extent can correlations between the various neuropsychological tests on the one hand, and sites of brain activity determined with fMRI on the other, be regarded as established. The extent to which these questions have yet received satisfactory answers is reviewed, and suggestions made both for improving correlations of neuropsychological tests with behavior as well as with the results of fMRI-based observations. PMID- 27393371 TI - Interpreting positive cultures in asymptomatic lung transplant recipients. PMID- 27393372 TI - Assessment of Health Risk from Historical Use of Cosmetic Talcum Powder. AB - This study's objective is to assess the risk of asbestos-related disease being contracted by past users of cosmetic talcum powder. To our knowledge, no risk assessment studies using exposure data from historical exposures or chamber simulations have been published. We conducted activity-based sampling with cosmetic talcum powder samples from five opened and previously used containers that are believed to have been first manufactured and sold in the 1960s and 1970s. These samples had been subject to conflicting claims of asbestos content; samples with the highest claimed asbestos content were tested. The tests were conducted in simulated-bathroom controlled chambers with volunteers who were talc users. Air sampling filters were prepared by direct preparation techniques and analyzed by phase contrast microscopy (PCM), transmission electron microscopy (TEM) with energy-dispersive x-ray (EDX) spectra, and selective area diffraction (SAED). TEM analysis for asbestos resulted in no confirmed asbestos fibers and only a single fiber classified as "ambiguous." Hypothetical treatment of this fiber as if it were asbestos yields a risk of 9.6 * 10-7 (under one in one million) for a lifetime user of this cosmetic talcum powder. The exposure levels associated with these results range from zero to levels far below those identified in the epidemiology literature as posing a risk for asbestos-related disease, and substantially below published historical environmental background levels. The approaches used for this study have potential application to exposure evaluations of other talc or asbestos-containing materials and consumer products. PMID- 27393373 TI - Viral load strategy: impact on risk behaviour and serocommunication of men who have sex with men in specialized care. AB - BACKGROUND: Incidence and prevalence of HIV are continuously high in German men, who have sex with men (MSM). Different transmission risk minimizing strategies have been observed. The viral load strategy rates patients unlikely to be sexually infectious if their viral load under effective therapy is stably suppressed during 6 months and no other sexually transmitted infections are present. OBJECTIVES: We aim to objectify the current popularity of the viral load strategy, the adherence to basic conditions and its impact on risk behaviour and serocommunication. Until now, no data on a German sample of HIV-positive MSM in regular specialized outpatient care are available. METHODS: Cross-sectional study with group comparisons between user group and non-user-group of the viral load strategy. Self-report questionnaires were conducted with 269 sexually active German HIV+MSM under effective treatment in specialized outpatient care. Structured interviews gathered additional information about approach to and realization of definite action levels concerning sexual risk behaviour and transmission risk minimizing strategies. RESULTS: Twenty-seven of 269 participants (10%) affirmed knowledge of having an undetectable viral load and stated this to be criteria for unprotected sexual behaviour. This subgroup reported more unprotected insertive (P = 0.018) and receptive anal intercourse (P = 0.042), more anonymous sex partners (P = 0.008) and less consistent safer sex. Analysing serocommunication, less addressing HIV/AIDS in general (P = 0.043) and less disclosing to sex partners (P = 0.023) was found, especially in anonymous settings. Differentiating serocommunication characteristics, a focus on seroguessing was depicted. CONCLUSIONS: The user group of the viral load strategy is small. But a less frequent, more reactive and assumptive serocommunication leads to an imprecise information exchange paired with higher frequency of risky behaviour, especially in anonymous settings, where frank serocommunication is often avoided. The targeted group of the viral load strategy diverges greatly from the user group. PMID- 27393375 TI - Effect of Hydroxytyrosol on Human Mesenchymal Stromal/Stem Cell Differentiation into Adipocytes and Osteoblasts. AB - BACKGROUND AND AIMS: Natural phenolic compounds are known for their antioxidant capacity, showing biological activity in numerous physiological processes. Such chemicals have been proposed for prevention or treatment of pathologies like osteoporosis and diabetes. One of these is hydroxytyrosol (HT), which may be involved in the differentiation of human mesenchymal stromal/stem cells (MSCs), which are precursors of osteoblasts and adipocytes. Yet, little information is available. Therefore, our objective was to study the possible effect of HT on MSC differentiation. METHODS: Differentiation markers were analyzed while human bone marrow MSCs were differentiated into osteoblasts or adipocytes in the presence of 1 or 100 MUmol HT. RESULTS: High HT concentrations repressed the expression of osteoblastic markers in MSCs differentiating into osteoblasts, whereas they increased the expression of adipogenic genes and the formation of fat vesicles in MSCs differentiating into adipocytes. CONCLUSIONS: High HT concentrations may inhibit osteoblastogenesis and promote adipogenesis, which can lead to bone loss. Therefore, the possible pharmacological use of extracts rich in HT should take into account this undesirable effect. PMID- 27393376 TI - A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema. AB - As treatment for breast cancer improves and the threat of life-long chronic lymphedema becomes more prevalent, the need for effective screening tools emerges as crucial. This review was conducted using literature beginning in 1992 to analyze primary research testing the accuracy of bioimpedance spectroscopy as a diagnostic and early detection tool for breast cancer-related lymphedema. We concluded bioimpedance is an accurate diagnostic tool for pre-existent lymphedema, however, it has not been validated for early detection. J. Surg. Oncol. 2016;114:537-542. (c) 2016 Wiley Periodicals, Inc. PMID- 27393374 TI - Dopamine D3 autoreceptor inhibition enhances cocaine potency at the dopamine transporter. AB - Cocaine is a commonly abused central nervous system stimulant that enhances dopamine (DA) neurotransmission through its ability to block dopamine transporters (DATs). Recent evidence suggests there may be an interaction between DATs and D2/D3 autoreceptors that modulates cocaine's effects. The purpose of this study was to explore how D2/D3 autoreceptors modulate the ability of cocaine to inhibit DA uptake through DATs on pre-synaptic DA terminals. Using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from male and female C57BL/6J mice, we first sought to examine the effects of global autoreceptor blockade using the non-selective D2/D3 autoreceptor antagonist, raclopride. We found that the ability of cocaine to inhibit DA uptake was increased by raclopride and that this effect was consistent across sexes. Furthermore, using D2 (L-741,626) or D3 (SB-277011-A) autoreceptor selective antagonists, we discovered that blockade of D3, but not D2, autoreceptors was responsible for the increased cocaine potency. Alterations in cocaine potency were attributable to alterations in uptake inhibition, rather than cocaine effects on vesicular DA release, suggesting that these results may be a product of a functional D3/DAT interaction apart from the canonical inhibitory actions of D3 autoreceptors on DA release. In addition, application of D2 (sumanirole) and D3 (PD 128907) autoreceptor-specific agonists had inverse effects, whereby D2 autoreceptor activation decreased cocaine potency and D3 autoreceptor activation had no effect. Together, these data show that DA autoreceptors dynamically regulate cocaine potency at the DAT, which is important for understanding cocaine's rewarding and addictive properties. We propose a model whereby presynaptic dopamine autoreceptors dynamically modulate cocaine potency through two separate mechanisms. We demonstrate that D2 agonists decrease cocaine potency, whereas D3 antagonists increase cocaine potency, likely through an allosteric mechanism outside of their canonical actions on dopamine release. These findings give important and novel insight into the contribution of D2/D3 autoreceptors to dopamine transporter function. PMID- 27393378 TI - [Not Available]. PMID- 27393377 TI - [Not Available]. AB - We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case) and loratadine (2(nd) case). PMID- 27393380 TI - Challenges and Hurdles to Business as Usual in Drug Development for Treatment of Rare Diseases. AB - Only 10-15 first-in-class new medicines are approved each year by the global pharmaceutical industry for all diseases, of which less than a third is for rare (orphan) diseases. The drug discovery processes to identify rare and common diseases are similar, suggesting it will be impossible to discover new drugs for even a small fraction of the rare diseases using the current paradigm. Different approaches are required to address this large unmet medical need. PMID- 27393379 TI - Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis. AB - Recombinant SjCystatin (rSjCystatin), a recombinant protein of Schistosoma japonicum cystatin, has been reported to have an effect on immunoregulation mediated by IL-10 induction. Rheumatoid arthritis (RA) is a common autoimmune inflammatory arthropathy, and recombinant immune-modulating drugs for RA treatment are under development. We aimed to study the putative immune regulation of rSjCystatin and its prophylactic/therapeutic effects on murine collagen induced arthritis (CIA). CIA was induced in DBA/1 mice by inoculation with bovine collagen II (CII). rSjCystatin was administered prior or post development of CIA. The severity of CIA was assessed using established clinical and histopathological scoring systems. The incidence was also determined. The CII-specific antibodies in sera and cytokines in splenocyte culture supernatants were measured by ELISA. Th1/Th2/Th17 cells and Tregs development in splenocytes were monitored by flow cytometry. The inflammatory mediators in the diseased joint were semiquantitated by qPCR. Prophylactic injection of rSjCystatin attenuated paw clinical scores, incidence, and histopathology scores of joints in CIA mice. The arthritis alleviative effects were closely associated with the augmentation of IL-4, IL-10, and collagen-specific IgG1, and with the distinct reduction of IFN-gamma, collagen-specific IgG2a, and the marked decrease of proinflammatory cytokines IL 6, IL-17, and TNF-alpha and RANKL. The data indicate that rSjCystatin may prevent cartilage destruction and inflammation of joints in CIA mice. The effects are related to the inhibitory modulation of Th1 and Th17 and upregulation of Tregs and Th2 via a shift of cytokines profiling from Th1 to Th2 response. PMID- 27393381 TI - No Effect of Anodal Transcranial Direct Current Stimulation on Gamma-Aminobutyric Acid Levels in Patients with Recurrent Mild Traumatic Brain Injury. AB - In patients in the chronic phase after recurrent mild traumatic brain injury (mTBI), alterations in gamma-aminobutyric acid (GABA) concentration and receptor activity have been reported, possibly mediating subtle but persistent cognitive deficits and increased rate of dementia in older age. We evaluated whether anodal transcranial direct current stimulation (atDCS) over the primary motor cortex reduces GABA concentration and GABAB receptor activity in patients with recurrent mTBI. Seventeen patients (mean age 25, two women) in the chronic phase after recurrent mTBI and 22 healthy control subjects (mean age 26, two women) were included. All participants received comprehensive cognitive testing and detailed questionnaires on post-concussive symptoms at baseline. Subsequently, they participated in four experimental sessions, consisting of either magnetic resonance spectroscopy (MRS)/atDCS/MRS, transcranial magnetic stimulation (TMS)/atDCS/TMS, MRS/sham/MRS, or TMS/sham/TMS to determine GABA concentration (from MRS) and GABAB receptor activity (from TMS) after atDCS and after sham stimulation. Patients with mTBI scored significantly lower on verbal fluency tasks compared with healthy control subjects. GABA concentration at baseline was associated with the number of mTBI, although no group differences in GABA concentration and GABAB receptor activity were found. Moreover, no effects of atDCS on GABA concentration and receptor activity were seen in patients with mTBI or healthy control subjects. GABA concentration may increase with the number of mTBI, but atDCS did not modulate GABA concentration and receptor activity, as has been reported previously. Specifics of experimental design and analysis, but also characteristics of the respective samples, may account for these differential findings, and should be addressed in future larger studies. PMID- 27393382 TI - Activation of the hypoxia-inducible factor pathway induced by prolyl hydroxylase domain 2 deficiency enhances the effect of running training in mice. AB - AIMS: Hypoxic response mediated by hypoxia-inducible factor (HIF) seems to contribute to the benefit of endurance training. To verify the direct contribution of HIF activation to running training without exposure to atmospheric hypoxia, we used prolyl hydroxylase domain 2 (PHD2) conditional knockout mice (cKO), which exhibit HIF activation independent of oxygen concentration, and we examined their maximal exercise capacity before and after 4 weeks of treadmill exercise training. METHODS: Phd2f/f mice (n = 26) and Phd2 cKO mice (n = 24) were randomly divided into two groups, trained and untrained, and were subjected to maximal running test before and after a 4-week treadmill training regimen. RESULTS: Prolyl hydroxylase domain 2 deficiency resulted in HIF alpha protein accumulation. Phd2 cKO mice exhibited marked increases in haematocrit values and haemoglobin concentrations, as well as an increase in the capillary number in the skeletal muscle. The 4-week training elicited an increase in the capillary-to-fibre (C/F) ratio and succinyl dehydrogenase activity of the skeletal muscle. Importantly, trained Phd2 cKO mice showed a significantly greater improvement in running time than trained control mice (P < 0.05). Collectively, these data suggest that the combination of training and the activation of the HIF pathway are important for maximizing the effect of running training. CONCLUSION: We conclude that the activation of the HIF pathway induced by PHD2 deficiency enhances the effect of running training. PMID- 27393383 TI - Predictors of postprandial hypotension in elderly patients with de novo Parkinson's disease. AB - Postprandial hypotension is one of the most important autonomic disorders in Parkinson's disease. However, its predictors remain unclear. We investigated which variable(s) predict the presence of postprandial hypotension in elderly patients with Parkinson's disease. The subjects were 64 patients with de novo Parkinson's disease who were 70 years or older. Postprandial hypotension was evaluated on a 75-g oral glucose tolerance test. Olfactory function, constipation, cardiac sympathetic or parasympathetic denervation, orthostatic intolerance on head-up tilt table testing, and other baseline characteristics were evaluated. The results showed the presence of postprandial hypotension was associated with severe dysosmia, constipation, orthostatic hypotension (a decrease in systolic blood pressure >=30 mmHg) and preprandial hypertension at rest. On multiple logistic regression analyses adjusted for age, sex, symptom duration, disease severity, and motor subtype, the odds ratio was 4.02 for severe dysosmia (p = 0.027), 9.99 for constipation (p = 0.006), 6.42 for orthostatic hypotension with alternative definition (p = 0.004) and 7.90 for preprandial hypertension at rest (p = 0.001). Each multiple logistic regression analysis revealed that female sex was also a risk factor for postprandial hypotension. The variables with the highest sensitivity and specificity for postprandial hypotension were constipation (89.6 %) and preprandial hypertension at rest or orthostatic hypotension with alternative definition (both 77.1 %), respectively. Our results suggest that these variables predict the presence of postprandial hypotension in elderly patients with Parkinson's disease, suggesting that postprandial hypotension shares etiologic factors with these potential predictors. PMID- 27393384 TI - Self-nonself discrimination by the complement system. AB - The alternative pathway (AP) of complement can recognize nonself structures by only two molecules, C3b and factor H. The AP deposits C3b covalently on nonself structures via an amplification system. The actual discrimination is performed by factor H, which has binding sites for polyanions (sialic acids, glycosaminoglycans, phospholipids). This robust recognition of 'self' protects our own intact viable cells and tissues, while activating structures are recognized by default. Foreign targets are opsonized for phagocytosis or killed. Mutations in factor H predispose to severe diseases. In hemolytic uremic syndrome, they promote complement attack against blood cells and vascular endothelial cells and lead, for example, to kidney and brain damage. Even pathogens can exploit factor H. In fact, the ability to bind factor H discriminates most pathogenic microbes from nonpathogenic ones. PMID- 27393386 TI - Molecular characteristics of lysozyme G in Euryglossa orientalis; cDNA cloning, phylogenic analysis, physicochemical properties and tissue gene expression. AB - Lysozymes are the key molecules of innate immune system against bacterial infections. In the present study, we identified the molecular characteristics, physicochemical properties, antibacterial activity, evolutionary relationship and tissue expression pattern of g-type lysozyme in Euryglossa orientalis (EuOr LysG). The full-length EuOr LysG cDNA is composed of 588 nucleotides and an open reading frame encoding a protein with 195 amino acids with more than 65 % identity to g-type lysozyme of Solea senegalensis (73 %) and Scophthalmus rhombus (64 %). Amino acid sequence alignment showed that EuOr LysG protein possessed a conserved catalytic motif (Glu71-Asp84-Asp101) and one predicted disulfide bond between Cys32 and Cys122. Phylogenetic analysis based on the g-type lysozyme sequences indicated that E. orientalis and other fish of Pleuronectiformes were diverged together in the evolutionary history. The K m and V max values of the recombinant EuOr LysG were 0.266 mg/ml of Micrococcus lysodeikticus as substrate and 667 U/mg of protein, respectively. The optimum temperature and pH of recombinant EuOr LysG were 45 and 6 degrees C, respectively. Real-time PCR analysis showed that EuOr LysG transcript was most abundant in head kidney and gill and less in muscle. We also showed that the EuOr LysG had potent lytic activity against major fish bacterial pathogens with the highest activity against Bacillus cereus and Aeromonas hydrophila. Bacterial challenge with Vibrio parahaemolyticus could upregulate LysG in immune-related tissues. Our results help to understand the molecular and physicochemical characteristics of g-type lysozyme in E. orientalis which might play an important role in host defense against the bacterial infection. PMID- 27393385 TI - Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma. AB - BACKGROUND: The PD-1/PD-L1 axis plays a paramount role in the immune escape of tumor cells by negative regulation of T-cell functions. The aim of the present study was to characterize the PD-L1 expression pattern and its clinical implication in soft-tissue sarcomas (STS). METHODS: We analyzed PD-L1 expression in 82 STS patients with 5 subtypes: rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma, epithelioid sarcoma, and mesenchymal chondrosarcoma. RESULTS: The median age at diagnosis was 26 (range: 1-78) and the male to female ratio was 1.6. The majority (80 %) of patients showed locoregional disease rather than metastatic disease at diagnosis. Thirty-five cases (43 %) showed PD-L1 expression and the proportion of PD-L1 expression was significantly different according to histologic subtypes (P = 0.004); highest in epithelioid sarcoma (100 %, 7/7), followed by synovial sarcoma (53 %, 10/19), rhabdomyosarcoma (38 %, 12/32), and Ewing sarcoma (33 %, 6/18), while it was not expressed in mesenchymal chondrosarcoma (0 %, 0/6). STS patients with PD-L1 expression had worse overall survival compared with those without PD-L1 expression (5-year survival rate: 48 % vs. 68 %, P = 0.015). The Cox proportional hazard model adjusted for histologic subtype, initial metastasis, and PD-L1 expression showed that PD-L1 expression was significantly associated with shorter overall survival (P = 0.037, HR 2.57, 95 % CI 1.060-6.231). CONCLUSION: We have confirmed PD-L1 expression in various STS of young population and demonstrated its independent negative prognostic role, thereby suggesting the PD-1/PD-L1 axis as a potential therapeutic target for the treatment of young STS patients. PMID- 27393387 TI - Practice Patterns Revisited in Pediatric Psychosomatic Medicine. AB - BACKGROUND: Given the heightened focus on the implementation of integrated care and population health management strategies, there is a critical need for an analysis of pediatric psychosomatic medicine (PPM) programs. OBJECTIVE: The goal was to survey current practice patterns in academic PPM programs in North America regarding their service composition, clinical consultation services, changes in service demand, funding, and major challenges so as to inform and support advocacy efforts on behalf of children in their need for responsive and effective PPM services. RESULTS: With a 52.5% survey response rate from 122 child and adolescent psychiatry programs in North America, the demand for PPM services was reported to have significantly increased over the past decade as seen in the described expansion in clinical consultation services and the reported higher patient acuity, as well as new responsibilities in the care of youth with psychiatric illnesses who require boarding on medical inpatient services. Although an increased willingness by hospital administrators to fund PPM services was apparent, adequate funding remained a core issue. Although the value of research is well recognized, few programs are engaged in systematic PPM investigation. CONCLUSION: This survey provides evidence that the current field of PPM appears to be in an increasingly stronger position within academic medical centers. It is just as apparent today, as it has been in the past, that there is a need to communicate at local, regional, and national levels that PPM is an essential behavioral health service. PMID- 27393388 TI - Treating Depression: What Patients Want; Findings From a Randomized Controlled Trial in Primary Care. AB - OBJECTIVE: To highlight clinical and sociodemographic factors associated with patients' preference in the treatment of depression, we conducted a randomized controlled trial comparing the efficacy of selective serotonin reuptake inhibitors and interpersonal counseling in patients with a major depressive episode. METHODS: Patients, recruited from a psychiatric consultation service in the primary care setting, were asked to express their preference for the type of treatment before randomization to one of the 2 intervention arms. Severity of depressive symptoms and functional impairment was assessed using the 21-item Hamilton Rating Scale for Depression and the Work and Social Adjustment Scale, respectively. RESULTS: A total of 170 patients were evaluated, 87 (51.2%) patients expressed their preference for interpersonal counseling and 83 (48.8%) for selective serotonin reuptake inhibitors. Depression severity and treatment preference showed significant correlations. Preference for interpersonal counseling was related to mild depression and greater functional impairment, whereas patients with moderate or severe depression were more likely to prefer medication. Remission rates and functional level were not related to treatment preference at the end of the study. CONCLUSION: Treatment preference is a critical factor, influenced by clinical and sociodemographic characteristics, and further studies are needed to improve its clinical relevance. PMID- 27393390 TI - Introducing a novel interaction model structure for the combined effect of temperature and pH on the microbial growth rate. AB - Efficient modelling of the microbial growth rate can be performed by combining the effects of individual conditions in a multiplicative way, known as the gamma concept. However, several studies have illustrated that interactions between different effects should be taken into account at stressing environmental conditions to achieve a more accurate description of the growth rate. In this research, a novel approach for modeling the interactions between the effects of environmental conditions on the microbial growth rate is introduced. As a case study, the effect of temperature and pH on the growth rate of Escherichia coli K12 is modeled, based on a set of computer controlled bioreactor experiments performed under static environmental conditions. The models compared in this case study are the gamma model, the model of Augustin and Carlier (2000), the model of Le Marc et al. (2002) and the novel multiplicative interaction model, developed in this paper. This novel model enables the separate identification of interactions between the effects of two (or more) environmental conditions. The comparison of these models focuses on the accuracy, interpretability and compatibility with efficient modeling approaches. Moreover, for the separate effects of temperature and pH, new cardinal parameter model structures are proposed. The novel interaction model contributes to a generic modeling approach, resulting in predictive models that are (i) accurate, (ii) easily identifiable with a limited work load, (iii) modular, and (iv) biologically interpretable. PMID- 27393389 TI - The transition of smooth muscle cells from a contractile to a migratory, phagocytic phenotype: direct demonstration of phenotypic modulation. AB - KEY POINTS: Smooth muscle cell (SMC) phenotypic conversion from a contractile to a migratory phenotype is proposed to underlie cardiovascular disease but its contribution to vascular remodelling and even its existence have recently been questioned. Tracking the fate of individual SMCs is difficult as no specific markers of migratory SMCs exist. This study used a novel, prolonged time-lapse imaging approach to continuously track the behaviour of unambiguously identified, fully differentiated SMCs. In response to serum, highly-elongated, contractile SMCs initially rounded up, before spreading and migrating and these migratory cells displayed clear phagocytic activity. This study provides a direct demonstration of the transition of fully contractile SMCs to a non-contractile, migratory phenotype with phagocytic capacity that may act as a macrophage-like cell. ABSTRACT: Atherosclerotic plaques are populated with smooth muscle cells (SMCs) and macrophages. SMCs are thought to accumulate in plaques because fully differentiated, contractile SMCs reprogramme into a 'synthetic' migratory phenotype, so-called phenotypic modulation, whilst plaque macrophages are thought to derive from blood-borne myeloid cells. Recently, these views have been challenged, with reports that SMC phenotypic modulation may not occur during vascular remodelling and that plaque macrophages may not be of haematopoietic origin. Following the fate of SMCs is complicated by the lack of specific markers for the migratory phenotype and direct demonstrations of phenotypic modulation are lacking. Therefore, we employed long-term, high-resolution, time-lapse microscopy to track the fate of unambiguously identified, fully-differentiated, contractile SMCs in response to the growth factors present in serum. Phenotypic modulation was clearly observed. The highly elongated, contractile SMCs initially rounded up, for 1-3 days, before spreading outwards. Once spread, the SMCs became motile and displayed dynamic cell-cell communication behaviours. Significantly, they also displayed clear evidence of phagocytic activity. This macrophage-like behaviour was confirmed by their internalisation of 1 MUm fluorescent latex beads. However, migratory SMCs did not uptake acetylated low-density lipoprotein or express the classic macrophage marker CD68. These results directly demonstrate that SMCs may rapidly undergo phenotypic modulation and develop phagocytic capabilities. Resident SMCs may provide a potential source of macrophages in vascular remodelling. PMID- 27393391 TI - Neuroimaging correlates of language network impairment and reorganization in temporal lobe epilepsy. AB - Advanced, noninvasive imaging has revolutionized our understanding of language networks in the brain and is reshaping our approach to the presurgical evaluation of patients with epilepsy. Functional magnetic resonance imaging (fMRI) has had the greatest impact, unveiling the complexity of language organization and reorganization in patients with epilepsy both pre- and postoperatively, while volumetric MRI and diffusion tensor imaging have led to a greater appreciation of structural and microstructural correlates of language dysfunction in different epilepsy syndromes. In this article, we review recent literature describing how unimodal and multimodal imaging has advanced our knowledge of language networks and their plasticity in epilepsy, with a focus on the most frequently studied epilepsy syndrome in adults, temporal lobe epilepsy (TLE). We also describe how new analytic techniques (i.e., graph theory) are leading to a refined characterization of abnormal brain connectivity, and how subject-specific imaging profiles combined with clinical data may enhance the prediction of both seizure and language outcomes following surgical interventions. PMID- 27393392 TI - ZiBu PiYin recipe prevents diabetes-associated cognitive decline in rats: possible involvement of ameliorating mitochondrial dysfunction, insulin resistance pathway and histopathological changes. AB - BACKGROUND: Disturbance in energy metabolism, as a key factor in diabetes associated cognitive decline (DACD), has become a promising therapeutic target of Chinese medicine ZiBu PiYin Recipe (ZBPYR). However, it is still not clear how ZBPYR affects the mitochondrial function in DACD rats' brains, which is considered as the crucial cell organelle to supply energy for the brain. METHODS: Type 2 diabetes mellitus (T2DM) rat models were established by using high fat diet and streptozotocin (STZ) (30 mg/kg, ip). The evaluation of insulin sensitivity was performed by oral glucose tolerance and insulin tolerance test. After 7 weeks, the T2DM rats were treated with vehicle or ZBPYR for 11 weeks and morris water maze (MWM) test were used to evaluate memory function. The ultra structural changes of prefrontal cortex (PFC) and hippocampus were examined by transmission electron microscopy (TEM). The mitochondrial membrane potential (DeltaPsim) and reactive oxygen species (ROS) were measured with JC-1 and DCFDA assay. The levels of insulin proteins were quantified by Western Blot analysis and the markers of histopathological changes were detected by immunohistochemistry. RESULTS: ZBPYR could alleviate learning and memory impairment of DACD rats. TEM showed that ZBPYR prevented mitochondrial ultra structural alterations and number changes in the PFC and hippocampus of the DACD rats. In addition, ZBPYR significantly increased DeltaPsim and lowered the levels of ROS. Further investigation indicated that ZBPYR suppressed the release of cytochrome c from mitochondria, strengthened insulin signaling and inhibited GSK3beta over-expression. These positive effects were associated with reduced Abeta1-42 deposition and restored expression levels of microtubule-associated protein MAP2. CONCLUSION: ZBPYR showed excellent protective effect against DACD via ameliorating mitochondrial dysfunction, insulin resistance and histopathological changes. PMID- 27393393 TI - [Not Available]. PMID- 27393394 TI - [Not Available]. PMID- 27393395 TI - [Not Available]. PMID- 27393396 TI - Biosimilars: from Technical to Pharmacoeconomic Considerations. AB - A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up. PMID- 27393397 TI - [Not Available]. PMID- 27393398 TI - [Not Available]. PMID- 27393399 TI - [Not Available]. PMID- 27393400 TI - MRI morphologic alterations after liver SBRT : Direct dose correlation with intermodal matching. AB - AIM: CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. PATIENTS AND METHODS: MRI data of 24 patients with liver metastases 7+/-3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD2,alpha/beta =x with alpha/beta values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. RESULTS: A central nonenhancing area was observed within the isodose lines of nominally 48.2 +/- 15.2 Gy, EQD2Gy/alpha/beta =10 92.5 +/- 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 +/- 15.3 Gy, EQD2Gy/alpha/beta =10 90.5 +/- 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 +/- 6.7 Gy (EQD2,alpha/beta =2 42.5 +/- 8.7 Gy, EQD2,alpha/beta =3 38.5 +/- 7.6 Gy, EQD2,alpha/beta =8 30.2 +/-6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 +/- 6.6 Gy (EQD2,alpha/beta=2 42.7 +/- 8.1 Gy, EQD2,alpha/beta=3 38.7 +/- 7 Gy; EQD2,alpha/beta=8 30.5 +/- 5.9 Gy). CONCLUSIONS: Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD2,alpha/beta =2-3) induce characteristic MRI morphologic alterations. PMID- 27393401 TI - [Not Available]. PMID- 27393403 TI - [Not Available]. PMID- 27393402 TI - The Conduct of Clinical Trials for Medicinal Products in Europe in the Light of the European Clinical Trials Directive. Review of Regulatory and Practical Aspects in the Different Countries. PMID- 27393404 TI - Integrity of Scientific Data: Transparency of Clinical Trial Data. AB - The integrity of the data from clinical trials and of its use is an essential element of the scientific method, and of the trust one can have in this method. There are many examples of fraud, and they recur regularly. The objective of this round table was to work on the definition of fraud, on its recognition and prevention especially in the institutional system. Fraud involves an active decision to cheat, and ranges from trying to hide incompetence to wholesale invention of data, patients or studies. Its frequency is difficult to evaluate but might be as high as 1% of all studies or publications. Fraud can involve ethics (post-hoc IRB [institutional review board] approval, IRB requests not applied, lack of consent), or any of the steps from realisation to interpretation of studies or trials. Identification of fraud is made harder by the usual risk for the whistleblowers, who must be protected. Seeking fraud is implicit in Good Clinical Practices (GCP) that all industry sponsors must apply, but that are less often applied by institutional sponsors. It might be useful to install procedures to detect fraud in studies, especially institutional. Various statistical methods can be used to identify unusual data patterns that could suggest fraud. Once fraud is identified, its management is often not foreseen. Here again, clear procedures or recommendations would be of help. PMID- 27393405 TI - [Not Available]. PMID- 27393406 TI - Guidelines for Clinical Research in Developing Countries. AB - On the basis of a review of current clinical research conditions in developing countries, guidelines have been formulated to ensure scientific validity as well as adherence to universal ethical principles. The main recommendation is that projects should be reviewed by two Institutional Review Boards, one in the country where the Study Sponsor is based, and another in the country where the study is being carried out. In addition, an independent Data Safety Monitoring Board should be set up and systems established to ensure the effective reporting of Serious Adverse Events and to specify the Sponsor's obligations after the end of the Study. PMID- 27393407 TI - [Not Available]. PMID- 27393408 TI - Biotherapies: Are they Just Like any Other Drugs? PMID- 27393409 TI - [Not Available]. AB - Le vaccin est un medicament biologique (le plus souvent anti-infectieux) administre dans un but le plus souvent preventif, dont l'effet n'est pas pharmacologique mais immunologique. Il doit etre evalue par les techniques habituelles de la pharmacologie clinique et de la pharmacovigilance, mais en tenant compte de ses particularites (mecanisme d'action, fabrication, administration le plus souvent a des sujets sains, modalites de prescription particulieres avec des recommandations mises a jour regulierement, protection a la fois individuelle et collective, etc.). Quelques experiences de campagnes vaccinales ont revele des insuffisances dans l'obtention des donnees permettant d'evaluer l'interet de sante publique d'un vaccin, son adaptation a l'epidemiologie recente de la maladie et sa securite d'emploi a long terme. L'absence de donnees peut generer des craintes relayees par les ligues anti vaccinales. Pour une meilleure pharmacovigilance des vaccins, il est necessaire : (i) d'ameliorer la coherence entre les instances d'evaluation, meme si des efforts ont ete recemment faits ; (ii) de completer les plans de gestion de risque par une surveillance microbiologique et epidemiologique active et par l'obtention des donnees necessaires au suivi de pharmacovigilance des populations exposees ; (iii) d'assurer l'enseignement sur la vaccination au sein de la communaute medicale, ainsi que l'education a la sante pour les populations. PMID- 27393410 TI - Which Pharmacovigilance for Vaccines? AB - Vaccines are not separate health products but anti-infectious medicines administered for the large part prophylactically and for which the effect is immunological and not pharmacological. They should be evaluated by the usual methods of clinical pharmacology and pharmacovigilance, taking into account certain specificities (mechanism of action, manufacture, frequent administration to healthy subjects, particular recommendations, etc.). Experience from some vaccination campaigns have revealed insufficiencies notably in data collection allowing evaluation of the interest of a vaccine to public health, its relevance to the recent epidemiology of the disease in question and long-term security. The absence of data can generate fear in the general population that is broadcast by anti-vaccination lobby. For a more optimal pharmacovigilance of vaccines, it is necessary to: (i) improve the coherence between the evaluating authorities; (ii) set up, in addition to the usual risk management plan, an active microbiological and epidemiological surveillance and to follow up exposed populations; (iii) have programmes of education of the medical community regarding vaccination and health education for the general public. PMID- 27393411 TI - Immunological aspects of congenital disorders of glycosylation (CDG): a review. AB - Congenital disorders of glycosylation (CDG) are a rapidly growing family of genetic diseases comprising more than 85 known distinct disorders. They show a great phenotypic variability ranging from multi-organ/system to mono-organ/system involvement with very mild to extremely severe expression. Immunological dysfunction has a significant impact on the phenotype in a minority of CDG. CDG with major immunological involvement are ALG12-CDG, MAGT1-CDG, MOGS-CDG, SLC35C1 CDG and PGM3-CDG. This review discusses the variety of immunological abnormalities reported in human CDG. Understanding the immunological aspects of CDG may contribute to a better management/treatment of these pathologies and possibly of more common diseases, such as inflammatory diseases. PMID- 27393413 TI - Combined inverse-forward artificial neural networks for fast and accurate estimation of the diffusion coefficients of cartilage based on multi-physics models. AB - Analytical and numerical methods have been used to extract essential engineering parameters such as elastic modulus, Poisson's ratio, permeability and diffusion coefficient from experimental data in various types of biological tissues. The major limitation associated with analytical techniques is that they are often only applicable to problems with simplified assumptions. Numerical multi-physics methods, on the other hand, enable minimizing the simplified assumptions but require substantial computational expertise, which is not always available. In this paper, we propose a novel approach that combines inverse and forward artificial neural networks (ANNs) which enables fast and accurate estimation of the diffusion coefficient of cartilage without any need for computational modeling. In this approach, an inverse ANN is trained using our multi-zone biphasic-solute finite-bath computational model of diffusion in cartilage to estimate the diffusion coefficient of the various zones of cartilage given the concentration-time curves. Robust estimation of the diffusion coefficients, however, requires introducing certain levels of stochastic variations during the training process. Determining the required level of stochastic variation is performed by coupling the inverse ANN with a forward ANN that receives the diffusion coefficient as input and returns the concentration-time curve as output. Combined together, forward-inverse ANNs enable computationally inexperienced users to obtain accurate and fast estimation of the diffusion coefficients of cartilage zones. The diffusion coefficients estimated using the proposed approach are compared with those determined using direct scanning of the parameter space as the optimization approach. It has been shown that both approaches yield comparable results. PMID- 27393412 TI - Antenatal manifestations of inborn errors of metabolism: biological diagnosis. AB - Inborn errors of metabolism (IEMs) that present with abnormal imaging findings in the second half of pregnancy are mainly lysosomal storage disorders (LSDs), cholesterol synthesis disorders (CSDs), glycogen storage disorder type IV (GSD IV), peroxisomal disorders, mitochondrial fatty acid oxidation defects (FAODs), organic acidurias, aminoacidopathies, congenital disorders of glycosylation (CDGs), and transaldolase deficiency. Their biological investigation requires fetal material. The supernatant of amniotic fluid (AF) is useful for the analysis of mucopolysaccharides, oligosaccharides, sialic acid, lysosphingolipids and some enzyme activities for LSDs, 7- and 8-dehydrocholesterol, desmosterol and lathosterol for CSDs, acylcarnitines for FAODs, organic acids for organic acidurias, and polyols for transaldolase deficiency. Cultured AF or fetal cells allow the measurement of enzyme activities for most IEMs, whole-cell assays, or metabolite measurements. The cultured cells or tissue samples taken after fetal death can be used for metabolic profiling, enzyme activities, and DNA extraction. Fetal blood can also be helpful. The identification of vacuolated cells orients toward an LSD, and plasma is useful for diagnosing peroxisomal disorders, FAODs, CSDs, some LSDs, and possibly CDGs and aminoacidopathies. We investigated AF of 1700 pregnancies after exclusion of frequent etiologies of nonimmune hydrops fetalis and identified 108 fetuses affected with LSDs (6.3 %), 29 of them with mucopolysaccharidosis type VII (MPS VII), and six with GSD IV (0.3 %). In the AF of 873 pregnancies, investigated because of intrauterine growth restriction and/or abnormal genitalia, we diagnosed 32 fetuses affected with Smith-Lemli Opitz syndrome (3.7 %). PMID- 27393414 TI - Measuring spatio-temporal parameters of uphill ski-mountaineering with ski-fixed inertial sensors. AB - In this study an algorithm designed for the diagonal stride in classical cross country skiing was adapted to compute spatio-temporal parameters for uphill ski mountaineering using a ski fixed inertial sensor. Cycle duration, thrust duration, cycle speed, cycle distance, elevation gain, and slope angle were computed and validated against a marker-based motion capture system during indoor treadmill skiing. Skiing movement of 12 experienced, recreational level athletes was measured for nine different speed and slope angle combinations. The accuracy (i.e. mean error) and precision (i.e. standard deviation of the error) were below 3ms and 13ms for the cycle duration and thrust duration, respectively. Accuracy (precision) for cycle speed, cycle distance and elevation gain were -0.013m/s (0.032m/s), -0.027m (0.018m), and 0.006m (0.011m), respectively. Slope angle accuracy and precision were 0.40 degrees and 0.32 degrees , respectively. If the cross-country skiing algorithm would be used without adaptations, errors would be up to one order of magnitude larger. The adapted algorithm proved valid for measuring spatio-temporal parameters for ski-mountaineering on treadmill. It is expected that the algorithm shows similar performance on snow. PMID- 27393415 TI - The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy. AB - PURPOSE: To investigate the usefulness of preimplantation genetic diagnosis (PGD) for the patient affected by congenital contractural arachnodactyly (CCA) and spinal and bulbar muscular atrophy (SBMA). METHODS: Multiple displacement amplification (MDA) was performed for whole genome amplification (WGA) of biopsied trophectoderm (TE) cells. Direct mutation detection by sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used for CCA diagnosis. Direct sequencing of the PCR products and sex determination by amplification of sex-determining region Y (SRY) gene were used for SBMA diagnosis. After PGD, the unaffected blastocyst (B4) was transferred in the following frozen embryo transfer (FET). RESULTS: In this PGD cycle, sixteen MII oocytes were inseminated by ICSI with testicular spermatozoa. Four blastocysts (B4, B5, B10, B13) were utilized for TE cell biopsy on day 5 after ICSI. After PGD, B4 was unaffected by CCA and SBMA. B5 was affected by CCA and carried SBMA. B10 was unaffected by CCA and carried SBMA. B13 was affected by CCA and unaffected by SBMA. B4 was the only unaffected blastocyst and transferred into the uterus for the subsequent FET cycle. The accuracy of PGD was confirmed by amniocentesis at 21 weeks of gestation. A healthy boy weighing 2850 g was born by cesarean section at the 38th week of gestation. CONCLUSIONS: PGD is a valid screening tool for patienst affected of CCA and SBMA to prevent transmission of these genetic diseases from parents to children. PMID- 27393416 TI - Loss of genetic diversity and increased embryonic mortality in non-native lizard populations. AB - Many populations are small and isolated with limited genetic variation and high risk of mating with close relatives. Inbreeding depression is suspected to contribute to extinction of wild populations, but the historical and demographic factors that contribute to reduced population viability are often difficult to tease apart. Replicated introduction events in non-native species can offer insights into this problem because they allow us to study how genetic variation and inbreeding depression are affected by demographic events (e.g. bottlenecks), genetic admixture and the extent and duration of isolation. Using detailed knowledge about the introduction history of 21 non-native populations of the wall lizard Podarcis muralis in England, we show greater loss of genetic diversity (estimated from microsatellite loci) in older populations and in populations from native regions of high diversity. Loss of genetic diversity was accompanied by higher embryonic mortality in non-native populations, suggesting that introduced populations are sufficiently inbred to jeopardize long-term viability. However, there was no statistical correlation between population-level genetic diversity and average embryonic mortality. Similarly, at the individual level, there was no correlation between female heterozygosity and clutch size, infertility or hatching success, or between embryo heterozygosity and mortality. We discuss these results in the context of human-mediated introductions and how the history of introductions can play a fundamental role in influencing individual and population fitness in non-native species. PMID- 27393417 TI - Expression of amphiregulin in mucoepidermoid carcinoma of the major salivary glands: a molecular and clinicopathological study. AB - In mucoepidermoid carcinoma (MEC), CRTC1-MAML2 fusion indicates a favorable prognosis. Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, has been shown to be a downstream target of CRTC1-MAML2 fusion, and to play a role in tumor growth and survival in CRTC1-MAML2-positive MEC cell lines. The aim of this study was to characterize the AREG and EGFR expression in the fusion-positive and fusion-negative MEC of the major salivary gland. The AREG and EGFR expression were studied by immunochemistry in 33 MEC cases of the major salivary glands. CRTC1-MAML2 fusion was tested by reverse-transcription polymerase chain reaction (23 CRTC1-MAML2 fusion-positive, 10 fusion-negative). Of 23 fusion-positive cases, AREG and EGFR overexpression were detected in 17 (73.9%) and 14 (60.9%) cases, respectively. Of 10 fusion-negative cases, AREG and EGFR overexpression were detected in 1 (10%) and 3 (30.0%) cases, respectively. There was a positive correlation between CRTC1-MAML2 fusion and AREG overexpression (P < .01), but not between CRTC1-MAML2 fusion and EGFR overexpression. The AREG overexpression was associated with a longer disease-free survival of the MEC patients (P = .042), but EGFR overexpression was not. In this study, we showed that AREG overexpression was detected more frequently in the CRTC1-MAML2 fusion-positive tumors than in fusion-negative tumors. Detection of AREG expression may be useful for identifying CRTC1-MAML2-positive MECs and as a marker for favorable prognosis. PMID- 27393418 TI - Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images. AB - Despite its great potential in studying brain anatomy and structure, diffusion magnetic resonance imaging (dMRI) is marred by artefacts more than any other commonly used MRI technique. In this paper we present a non-parametric framework for detecting and correcting dMRI outliers (signal loss) caused by subject motion. Signal loss (dropout) affecting a whole slice, or a large connected region of a slice, is frequently observed in diffusion weighted images, leading to a set of unusable measurements. This is caused by bulk (subject or physiological) motion during the diffusion encoding part of the imaging sequence. We suggest a method to detect slices affected by signal loss and replace them by a non-parametric prediction, in order to minimise their impact on subsequent analysis. The outlier detection and replacement, as well as correction of other dMRI distortions (susceptibility-induced distortions, eddy currents (EC) and subject motion) are performed within a single framework, allowing the use of an integrated approach for distortion correction. Highly realistic simulations have been used to evaluate the method with respect to its ability to detect outliers (types 1 and 2 errors), the impact of outliers on retrospective correction of movement and distortion and the impact on estimation of commonly used diffusion tensor metrics, such as fractional anisotropy (FA) and mean diffusivity (MD). Data from a large imaging project studying older adults (the Whitehall Imaging sub-study) was used to demonstrate the utility of the method when applied to datasets with severe subject movement. The results indicate high sensitivity and specificity for detecting outliers and that their deleterious effects on FA and MD can be almost completely corrected. PMID- 27393419 TI - Transcranial alternating current stimulation modulates spontaneous low frequency fluctuations as measured with fMRI. AB - Transcranial alternating current stimulation (tACS) is a promising tool for modulating brain oscillations. Combining tACS with functional magnetic resonance imaging (fMRI), we recently showed that tACS applied over the occipital cortex did not exert its strongest effect on regions below the electrodes, but mainly on more distant fronto-parietal regions. Theoretically, this effect could be explained by tACS-induced modulation of functional connectivity between directly stimulated areas and more distant but anatomically and functionally connected regions. In the present study, we aimed to characterize the effect of tACS on low frequency fMRI signal fluctuations. We employed simultaneous fMRI-tACS in 20 subjects during resting state (eyes open with central fixation for ~8min). Subjects received tACS at different frequencies (10, 16, 40Hz) and with different electrode montages (Cz-Oz, P5-P6) previously used in behavioral studies. Electric field simulations showed that tACS over Cz-Oz directly stimulates occipital cortex, while tACS over P5-P6 primarily targets parietal cortices. Group-level simulation-based functional connectivity maps for Cz-Oz and P5-P6 resembled the visual and fronto-parietal control resting-state networks, respectively. The effects of tACS were frequency and partly electrode montage dependent. In regions where frequency-dependent effects of tACS were observed, 10 and 40Hz tACS generally induced opposite effects. Most tACS effects on functional connectivity were observed between, as opposed to within, resting-state networks. The left fronto-parietal control network showed the most extensive frequency-dependent modulation in functional connectivity, mainly with occipito-parietal regions, where 10Hz tACS increased and 40Hz tACS decreased correlation values. Taken together, our results show that tACS modulates local spontaneous low frequency fluctuations and their correlations with more distant regions, which should be taken into account when interpreting tACS effects on brain function. PMID- 27393421 TI - Facing mixed emotions: Analytic and holistic perception of facial emotion expressions engages separate brain networks. AB - The ability to decode facial emotions is of primary importance for human social interactions; yet, it is still debated how we analyze faces to determine their expression. Here we compared the processing of emotional face expressions through holistic integration and/or local analysis of visual features, and determined which brain systems mediate these distinct processes. Behavioral, physiological, and brain responses to happy and angry faces were assessed by presenting congruent global configurations of expressions (e.g., happy top+happy bottom), incongruent composite configurations (e.g., angry top+happy bottom), and isolated features (e.g. happy top only). Top and bottom parts were always from the same individual. Twenty-six healthy volunteers were scanned using fMRI while they classified the expression in either the top or the bottom face part but ignored information in the other non-target part. Results indicate that the recognition of happy and anger expressions is neither strictly holistic nor analytic Both routes were involved, but with a different role for analytic and holistic information depending on the emotion type, and different weights of local features between happy and anger expressions. Dissociable neural pathways were engaged depending on emotional face configurations. In particular, regions within the face processing network differed in their sensitivity to holistic expression information, which predominantly activated fusiform, inferior occipital areas and amygdala when internal features were congruent (i.e. template matching), whereas more local analysis of independent features preferentially engaged STS and prefrontal areas (IFG/OFC) in the context of full face configurations, but early visual areas and pulvinar when seen in isolated parts. Collectively, these findings suggest that facial emotion recognition recruits separate, but interactive dorsal and ventral routes within the face processing networks, whose engagement may be shaped by reciprocal interactions and modulated by task demands. PMID- 27393420 TI - Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration. AB - Connectivity-based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting-state fMRI data and a novel, data-driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within-parcel homogeneity and high reproducibility across animals. Graph analysis of the whole brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains. PMID- 27393422 TI - The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors. AB - Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN) melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross-species promoter analysis identified specific DNA binding sites in the DHN melanin biosynthesis genes pksP-arp1 intergenic region that can be recognized by bHLH and MADS-box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS-box) interfered with sporulation and reduced the expression of the DHN-melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region. PMID- 27393423 TI - Preclinical modeling and multimodality imaging of chronic myocardial infarction in minipigs induced by novel interventional embolization technique. AB - BACKGROUND: This study was designed to establish a chronic myocardial infarction (MI) model in minipigs with a novel coronary sequential balloons-sponge embolism technique. METHODS: Eighteen healthy minipigs (25-30 kg) were randomly divided into three groups for left anterior descending artery (LAD) occlusion: conventional balloon occlusion group (BO group, temporary balloon occlusion for 60 mins), half-balloon embolism group (HB group), and sequential balloon-balloon sponge embolism group (BBS group, two half-balloons with one sponge as the embolism clot). The incidence of ventricular fibrillation (VF), total mortality, operating time, and vascular recanalization 3 months post-MI was recorded and compared. Echocardiography, multimodality nuclear medical imaging, and histology staining were applied for the evaluation of infarction. RESULTS: Thirteen out of 18 minipigs survived after the operation, while 5 animals died with VF (3 in the BO group, 1 in the HB group, and 1 in the BBS group), with an 83.3 % (5/6 minipigs) acute procedural survival rate in embolism groups. The operating duration was 60.0 +/- 0.5 mins, 21.4 +/- 5.2 mins, and 31.2 +/- 4.7 mins in the three groups, respectively. LAD recanalization was found in three animals of the HB group but none in the BBS group by angiography follow-up. The infarct sizes were more stable and larger in the HB group and BBS group than that in the BO group (P < 0.05, n = 13). CONCLUSIONS: The method of sequential balloons-sponge embolization could induce myocardial infarction with consistent and sustained embolization and gain higher operation success rate and better repeatability in minipigs, which holds a promising method for preclinical MI study. PMID- 27393424 TI - Simultaneous quantitative analysis of multi-compounds by a single marker in Radix Astragali by using serum HPLC-MS feature. AB - Using the serum pharmacochemistry method for Chinese Medicine, the material basis of Radix Astragali (RA) for "regulating and enriching blood" was studied. By compared with blank blood sample as a positive control in adult Wistar rats, four original saponinsas the material basis for "regulating and enriching blood" were absorbed into the blood after oral administration of RA. They were identified as astragaloside, astragaloside, astragaloside and astragaloside by HPLC-MS. According to the constituents absorbed into blood, the extracts of RA were prepared. In addition, the present patterns of quality control are limited to industrial application because most of the natural standard ingredients are very expensive and unavailable. Therefore, a quantitative analysis method of multi components with a single marker (QAMS) was established and used to simultaneously measure four saponins from RA absorbed into the blood (Astragaloside, astragaloside, astragaloside and astragaloside). We used astragaloside I as the reference, the relative correction factors (f) of the other three saponins were measured by HPLC-MS. Within the linear ranges, the values of f of astragaloside I to astragaloside IV, astragaloside III and astragaloside II were 0.533, 0.779 and 0.934, respectively. According to the f values, we simultaneously determined four saponins using only one marker. The results of QAMS method were validated compared to that of external standard method, and no significant difference was observed. PMID- 27393425 TI - Dry and ripe fruit of Aegle marmelos. L: A potent source of antioxidant, lipoxygenase inhibitors and free radical scavenger. AB - The antioxidant, lipoxygenase inhibitory activities and free radical scavenging capacity of the crude extract, aqueous and some organic fractions of dry and ripe fruit of Aeglemarmelos. L were studied to understand the protective and therapeutic role for the use of the fruit as a remedy in different ailments. All the tested fractions and extracts showed to possess significant antioxidant, free radical scavenging capacity and lipoxygenase inhibitory potential. However, chloroform and aqueous fractions showed significant ability to quench radicals, to reduce ferric chloride and to inhibit soyabean lipoxygenase. Their antioxidant and lipoxygenase inhibition was estimated by IC50 values, for antioxidant ranging from 88-65% activity at concentration of 5-0.15MU/mL and similarly for lipoxygenase inhibition ranging from 89-69% at various concentrations of 5 0.15MU/mL, in chloroform and aqueous fractions respectively. The scavenger molecules in the dry and ripe fruit of A. marmelos may attribute to therapeutic and protective effect during different progressive stages of ailments. PMID- 27393426 TI - Nephroprotective effects of b-carotene on ACE gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity in rats. AB - beta -carotene is one of carotenoid natural pigments, which are produced by plants and are accountable for the bright colors of various fruits and vegetables. These pigments have been widely studied for their ability to prevent chronic diseases and toxicities. This study was designed to evaluate the effects of beta-carotene on angiotensin converting enzyme (ACE) gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity. Total 24 albino wistar rats of male sex (200-250gm) were divided into 6 groups as Group-1: The control remained untreated; Group-2: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks; Group-3: Received beta-carotene orally (200mg/kg b.w), for 24 weeks; and Group-4: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks + received beta-carotene orally (200mg/kg b.w), for further 12 weeks. The expression of ACE gene in thioacetamide induced renal toxicity in rats as well as supplemented with beta-carotene was investigated and compared their level with control groups by using the quantitative RT-PCR method. The ACE gene expression was significantly increase in TAA rats as compare to control rats specifies that TAA induced changes in ACE gene of kidney, elevated renal ACE has been correlated with increase hypertensive end organ renal damage. The quantity of ACE gene were diminish in our rats who received beta-Carotene after TAA is administered, for this reason they seemed to be defended against increased ACE levels in kidney bought by TAA. In pre- and post-treatment groups, we studied the role of beta-Carotene against thioacetamide in the kidney of Wistar rats. Experimental confirmation from our study illustrates that beta-Carotene can certainly work as a successful radical-trapping antioxidant our results proved that TAA injury increased lipid peroxidation and diminish antioxidant GSH, SOD and CAT in renal tissue. Since beta-Carotene administration recover renal lipid peroxidation and antioxidants, it give the impression that beta-Carotene protects renal tissue against thioacetamide-induced oxidative damage. PMID- 27393427 TI - Antimicrobial activity of novel chitosan/cloisite 10A nanocomposite: Preparation, optimization, characterization and drug delivery behavior. AB - The objectives of the present research project were to formulate, evaluate and perform antimicrobial study and drug delivery behavior of nanocomposite material based on biopolymer chitosan and organically modified montmorillonite clay; i.e. cloisite 10A. In the present study, chitosan / cloisite 10A nanocomposite material was formulated by solution mixing and optimized. The nanocomposite material was characterized by FTIR, zeta sizer, XRD, and SEM. Polymer/clay nanocomposite material is evaluated for its antimicrobial activity against both gram- negative and gram- positive bacteria. It was also studied for potential drug carrier system using diclofenac sodium as a model drug. Drug incorporation efficiency and drug content were also determined. SEM provided the composite shape and its surface topography. XRD data revealed the nanocrystalline composition and crystallite size. The average diameters of particles in the nanocomposite were found to be around 80 nm from both XRD report, calculated by applying Scherrer equation and zeta sizer. The antimicrobial activity report revealed that nanocomposite exhibited stronger inhibition against the microorganisms as compared to that of pure chitosan. From the in vitro drug release study, it is observed that biopolymer/clay nanocomposite exhibited extended release period of drug as compared to the pristine chitosan. This research work provides a platform for further research on the polymer/clay nanocomposites for biomedical and drug delivery applications. PMID- 27393428 TI - Single dose pharmacokinetics of atorvastatin oral formulations using a simple HPLC-UV method. AB - The study was aimed to assess pharmacokinetics of atorvastatin (40 mg) in healthy fasted human subjects by a simple and inexpensive high performance liquid chromatography. Experimental design of the study was a randomized, two way, two periods, crossover study (single dose in fasted conditions). Eighteen (18) healthy male volunteers were enrolled according to FDA guidelines. The plasma samples were assayed using an isocratic High Performance Liquid Chromatography (HPLC) system of Agilent technologies USA consisted of an isocratic pump with column of Thermo Electron Corporation USA (ODS hypersil C(18) 4.6 mm x 250 mm), a UV-visible detector set at lambda(max) 237 nm. Maximum plasma concentrations (C(max)) of atorvastatin (Mean +/- SEM) for the reference product (A) found to be 13.739+/-0.210ng/ml & 13.374+/-0.145ng/ml for test product (B). T(max) values (Mean+/-SEM) of atorvastatin were 1.222 +/-0.060 hours and 1.167+/-0.057 hours for reference and test products, respectively. The values of AUC(0-oo) (Mean +/- SEM) for the reference (A) and test product (B) were 73.955 +/- 1.715ng.h/ml and 77.773 +/- 1.858ng. h/ml, respectively. Other pharmacokinetic parameters of both products were also determined. A statistical non-significant difference between pharmacokinetic parameters has been found and both brands of atorvastatin showed the same rate and extent of absorption in healthy fasted human volunteers after single dose. A simple and cost effective HPLC method was developed and applied. PMID- 27393429 TI - Screening for antibiofilm and antioxidant potential of turmeric (Curcuma longa) extracts. AB - The antibiofilm and antioxidant activities associated with turmeric were the main focus of the study. Antibacterial activity was explored against bacteria isolated from dental plaques and dental unit water lines exhibiting resistance against antibiotics and biocides respectively. This study provides a comparison of the natural plant extract against synthetic mouthwash, chemicals and commonly prescribed antibiotics. Methanol extract was more effective as compared to other extracts. Minimum inhibitory concentrations (MIC) ranged from 2.5-10mg/ml. Time based killing kinetic assay showed a significant reduction of bacterial load with increasing concentration of turmeric. Micro titer plate assay indicated significant inhibition of biofilm formation in cells treated with turmeric extract. Phytochemical screening of plant extracts showed the presence of vital secondary metabolites. Flavonoid content and total phenolic content varied among extracts, phenolic content for methanolic extract was 61.669 mg GAE/ gm dry extract and flavonoid content was 3.119mg quercitin/gm dry extract. The values of ferric reducing power were in the range of 5.55- 15.55 mmol of FeSO4 equivalent/ liter of the extract. Antioxidant activities and total phenolic content of the turmeric extracts had significant positive correlation. On the basis of these results turmeric may confidently be recommended as natural antibiofilm and antioxidant agent. PMID- 27393430 TI - Isolation and identification of antiproliferative compounds from the roots of Tetrastigma hemsleyanum against MDA-MB-435S cell lines. AB - This present study aimed to elucidate antiproliferative activity of four extracts (CHCl(3), EtOAc, n-BuOH and H(2)O) and chemical constituents isolated from the most potent extract of Tetrastigma hemsleyanum Diels et. Gilg (TDG) against MDA MB-435S cell lines using the MTT assay at various concentrations in vitro. Ten compounds were isolated and identified as (1) beta-sitosterol, (2) palmitic acid, (3) protocatechuic acid, (4) salicylic acid, (5) p-hydroxybenzoic acid, (6) resveratrol, (7) trans-4-hydroxycinnamic acid, (8) kaempferol, (9) quercetin, and (10) isoquercitrin. Compounds 3, 5-7, 10 were the first report of isolation from this plant. Moreover, antiproliferative activity displayed that the CHCl(3), H(2)O extracts and compounds 6, 8 exhibited obvious inhibitory effects on MDA-MB 435S cell lines with IC(50) values 100.28+/- 2.64, 127.48+/-3.45, 92.39+/-1.68 and 120.30+/-1.97MU/mL, respectively. Thus the obtained results indicate antiproliferative activity of TDG against MDA-MB-435S cell lines is ascribable to the most potent CHCl(3) extract along with active compounds 6 and 8, which could be considered as a potential chemotherapeutic agent in breast cancer. PMID- 27393431 TI - Assessment of antioxidant capacities and phenolic contents of nigerian cultivars of onions (Allium cepa L) and garlic (Allium sativum L). AB - This report assessed and compared the antioxidant potentials, quantities of ascorbic acid and phenolic compounds in methanolic extract of varieties of onions and garlic cultivars in Nigeria. The pH and total acidity of the extracts were equally determined. Antioxidancy of the cultivars were analysed using the in vitro assay techniques with 2,2-diphenyl-1-picryl Hydrazyl (DPPH) free radical scavenging and ferric reducing capacity. Ascorbic acid phenolic content were determined by volumetric and Folin-Ciocalteu's method respectively. The pH and total acidity were respectively 5.65 and 0.150mmol/L (red onion), 5.69 and 0.123mmol/L (white onion) and 6.94 and 0.105mmol/L (garlic). Red onion had the highest value of total phenols, ascorbic acid and free radical scavenging activity of 14.25+/-0.35mg GAE/ml, 229.098mg/100g, 66.44% respectively. In DPPH assay, red and white onion showed higher tendency to inhibit auto-oxidation when compared to garlic. The ferric reducing ability was greatest in garlic and least in white onions. These data indicate that with respect to antioxidant activity, red onion variety has highest health promoting potential among others. PMID- 27393432 TI - Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats. AB - The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-alpha (TNF- alpha) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents. PMID- 27393433 TI - Execution of strands thinning improves the phytochemicals and sugars profiling in date palm (Phoenix dactylifera L.) fruit. AB - Date fruit is a rich and quick source of phytochemicals and sugars (glucose, fructose, sucrose) which playing a vital role to nourish the human beings worldwide. The present study therefore, was conducted to explore the role of strands thinning on phytochemicals and sugars profiling in date palm (Cvs. Hillawi and Khadrawi). The experiment was comprised of different strand thinning treatments viz. @ 20% RCS (removal of central strands), 30% RCS, 20% STT (shortening of terminal tips), 30% STT, 20% RCS + 20% STT and 30% RCS+30% STT) including control. The results obtained from the current study showed that strand thinning significantly improves the level of phytochemicals and sugars in date fruit harvested at rutab stage as compared to un-thinned fruit clusters. Higher level of phytochemicals and sugars were found in fruit clusters thinned @ 30% RCS alone and in combination of 30% RCS+30%STT than other fruit thinning intensities. In conclusion; Strand thinning should be employed as an imperative managerial approach to improve the nutritional and phytochemical value of date palm fruit and to fulfill the quick energy requirement of the human body. PMID- 27393434 TI - Protective potential of the methanol extract of Macrothelypteris oligophlebia rhizomes for chronic non-bacterial prostatitis in rats. AB - The protective potential of the methanol extract of Macrothelypteris oligophlebia rhizomes (MMO) for chronic non-bacterial prostatitis (CNP) in rats was investigated in the present study. Carrageenan-induced CNP in rats was established. Fifty rats were randomly divided into sham-operated (sham-ope) group, model group, positive control group (Cernilton at a dose of 148mg/kg body weight) and two MMO-treated groups (MMO at doses of 600mg/kg and 300 mg/kg body weight). The anti-prostatitis effect was evaluated by prostate index, the levels of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), and histopathological examination. After 20 days of administration, MMO could significantly decrease prostate index and the levels of IL-10, TNF-alpha COX-2 and PGE2 in serum and could improve the prostate morphology in comparison with the model group. In summary, these results suggest that MMO possesses protective effects on prostate, which might be beneficial to further development for the treatment of CNP. PMID- 27393435 TI - Role of growth media and chemical enhancers in secondary metabolites production from Aspergillus carbonarius (NRL-369) and their pharmaceutical potentials. AB - The present study investigates the effect of different growth media and chemical enhancer on silent genes in Aspergillus carbonarius (NRL-369) for secondary metabolites production and its in vitro biological activities. Results revealed that Aspergillus carbonarius (NRL-369) grown in Czapeak yeast extract broth medium produced more metabolites compared with other media. Chemical epigenetic modifiers (suberoyl-anilide hydroxamic acid (SAHA) and 5-azacytidine (5-AZA) at concentration of 15mM were effective for the expression of silent genes resulting in increased secondary metabolites production. Secondary metabolites extracted in ethyl acetate and fractionized in n-Hexane showed variable degree of growth inhibitions of the tested microorganisms. Similarly, these samples were also active against brine shrimps and Lemna. PMID- 27393436 TI - Designing of a phytosome dosage form with Tecomella undulata as a novel drug delivery for better utilization. AB - In recent past scientists are moving for the novel herbal medicines for treatment of almost all diseases as they have no or lesser adverse effects as compared with modern allopathic medicines. The potency of any dosage form is depending on effective drug delivery level of any therapeutically active drug molecule. Phytosome is a novel approach to drug delivery system that produce more absorption and utilization than conventional herbal extracts and shows enhanced bioavailability. The present investigation is to prepare and evaluate phytosomes of Tecomella undulata using aqueous extract of its stem bark and lecithin. Solvent evaporation method was used for preparation of phytosomes. Phytosomes were studied for their evaluation parameters such as morphology, release character, drug entrapment efficiency, size of particles and charge on surface. Phytosomes were successfully developed and having unilemellar vesicles, good entrapment efficiency and drug release in nano sizes (up to 90%) and average particle size 153.2 nm with -23.7 mv charge on their surface. The results showed that the phytosomes can improve the bioavailability without resorting any pharmacological adjuvant or structural modification of the ingredients. PMID- 27393437 TI - Monitoring of glucose, salt and pure water in human whole blood: An in vitro study. AB - Designing and implementation of non-invasive methods for glucose monitoring in blood is main focus of biomedical scientists to provide a relief from skin puncturing of diabete patient. The objective of this research work is to investigate the shape deformations and the aggregation of red blood cells (RBCs) in the human blood after addition of three different analytes i) (0mM-400mM: Range) of glucose (C(6)H(12)O(6)), ii) (0mM-400mM: range) of pure salt (NaCl) and iii) (0mM- 350mM: range) of pure water (H(2)O). We have observed that the changes in the shape of individual cells from biconcave discs to spherical shapes and eventually the lysis of the cells at optimum concentration of glucose, salts and pure water. This demonstration also provides a base line to facilitate diabetes during partial diagnosis and monitoring of the glucose levels qualitatively both in research laboratories and clinical environment. PMID- 27393438 TI - Comparison of toxic heavy metals concentration in medicinal plants and their respective branded herbal formulations commonly available in Khyber Pakhtunkhwa. AB - The present study was conducted on fifteen medicinal plants and their respective branded formulations, commonly used in Khyber Pakhtunkhwa, for the evaluation of toxic heavy metals. The purpose of the study was to assess the toxic profile of the crude medicinal plants with respect to the worldwide permissible limits of metal concentrations and to correlate it with their respective herbal formulations available on the market. Chromium (Cr), Copper (Cu), Lead (Pb), Manganese (Mn) and Nickel (Ni) content were evaluated using wet digestion and Atomic Absorption Spectrophotometry technique. The results exhibited that in 100% of the analyzed medicinal plants Cr and Ni are present in excess of the maximum limits, Cu and Pb in 73% and 60% respectively, while Mn is in the normal range. Likewise in the respective branded formulations Cr and Ni exceed the normal limit in 100% of the products, Cu and Pb in 27% and 20% of the products respectively, while Mn is in the normal range. It indicates that majority of people in Pakistan who frequently use herbal drugs in various forms are exposed to the hazardous elements, which may pose serious health effects. Regulatory measures should therefore be taken to protect the general public from their hazardous health effects. PMID- 27393439 TI - Efficacy of methanolic extract of green and black teas against extended-spectrum beta-Lactamase-producing Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is one of the major bacteria causing acute infections. beta-Lactamase production is the principal defense mechanism in gram-negative bacteria. The aim of our study was to evaluate the antibacterial activity of Methanolic Extracts of Green and Black Teas on P. aeruginosa Extended Spectrum beta-Lactamases (ESBLs) production. This research was carried out on burn wounds of 245 hospitalized patients in Kerman, Iran. P. aeruginosa ESBLs and MBL producing strains were detected by Combination Disk Diffusion Test (CDDT) and Epsilometer test (E-test) strips, respectively. Minimum inhibitory concentration (MIC) was measured for Ceftazidime, Meropenem, Imipenem, Aztreonam, Cefotaxime and methanollic extracts of Camellia Sinensis (Green Tea). From 245 patients in the burn ward, 120 cases were infected with P. aeruginosa. 41 isolates contained ESBL while MBL was not detected. P. aeruginosa were resistant to Cefotaxime, Aztreonam, Ceftazidime, Meropenem and Imipenem, 72 (60%), 50 (41.66%), 79 (65.83%), 33 (27.5%) and 24 (20%), respectively. Green tea extract had the highest anti-bacterial effect on standard and P. aeruginosa strains in 1.25mg/ml concentration. This study determined that the methanolic extract of green tea has a higher effect against ESBL producing P. aeruginosa than Cefotaxime, Aztreonam and Ceftazidime. PMID- 27393440 TI - Evaluation of antiviral activity of plant extracts against foot and mouth disease virus in vitro. AB - The aim of this study was to evaluate antiviral activity of chloroformic leaves extracts of three plants: Azadirachta indica, Moringa oleifera and Morus alba against Foot and Mouth disease virus using MTT assay (3-(4, 5-Dimethylthiazol-2 yl)-2, 5-diphenyltetrazolium bromide). Antiviral and cytotoxic activity of each extract was evaluated as cell survival percentage and results were expressed as Means +/- S.D. The concentrations which resulted in cell survival percentages of greater than 50% are considered to be effective antiviral concentrations. From the tested plant extracts, Moringa oleifera showed potent antiviral activity (p<0.05) while Azadirachta indica showed significant antiviral activity in the range of 1-50MU/ml & 12-100MU/ml respectively. In contrast no antiviral activity was observed by Morus alba as all the tested concentration resulted in significant reduction (p<0.05) in cell survival percentage. PMID- 27393441 TI - Determination of contents of four alkaloids in Pericarpium arecae by quantitative analysis of multi-components by single-marker. AB - By using a typical component in traditional Chinese medicine Pericarpium Arecae (PA), quantitative analysis of multi-components by single-marker (QAMS) was performed to determine the contents of four alkaloids. With a column packed with strong cation exchange bonded silica particles, the alkaloids were well separated, showing linear relationships within certain ranges. The limit of detection, limit of quantitation, precision, stability, repeatability and recovery all met requirements. By employing arecoline as internal standard, relative correction factors for arecaidine, guvacine and guvacoline at five concentrations were detected with three HPLC systems and three HPLC columns. The peaks of arecaidine, guvacine and guvacoline were positioned, during which the columns with the same packing materials from different manufacturers significantly affected relative retention values and retention time differences of the alkaloids. However, the columns, from different batches, managed to give relative retention values satisfying the requirements of HPLC peak positioning. The Thermo Fisher Scientific column packed with strong cation exchange bonded silica particles was finally selected by considering resolution and peak time. Compared with the external standard method, QAMS detected the alkaloid contents in 12 PA samples more accurately and reliably. The results provide valuable evidence for content determination and quality control of alkaloids in PA. PMID- 27393442 TI - Intermediate release formulations of diclofenac potassium tablets for IVIVC. AB - In recent days response surface methodology (RSM) has widely been applied for development and optimization of cost effective formulations with required quality. Study comprised of three steps including micromeritic comparison of different powder blends of placebo and diclofenac potassium (DP), formulation designing with CCRD (Design Expert, version 7.0.0), and stability testing of selected formulations by using R Gui. Ten formulations (F11-F20) were developed using microcrystalline cellulose (Avicel PH-102) (X1) (13-72%), methocel K15M (X2) (6.59-23.4%) and magnesium stearate (X3) (1.32-4.68%), while responses were % friability and % drug release. Blending rate constant was determined at 3, 6, 9 and 12 minutes. The results of physicochemical parameters were found within acceptable limits. After in vitro testing at pH 1.2, pH 4.5 and pH 6.8, mechanism of drug release, kinetic analysis and statistical evaluation were carried out by model - independent, model-dependent and one-way ANOVA methods. Most formulations followed zero order kinetics at higher pH. Fickian release (0.326 <= n <=0.449) was observed with beta greater than 0.5 and less than 1. ANOVA indicated no significant variation within and between formulations as p-values were found to be > 0.05. PMID- 27393443 TI - Chemical composition, antioxidant and antimicrobial effects of Tunisian Limoniastrum guyonianum Durieu ex Boiss extracts. AB - In the present investigation, extracts obtained from L. guyonianum Durieu ex Boiss. aerial parts were used to evaluate total phenolic, flavonoid and tannin contents. A study of antioxidant activities of the prepared samples was carried out on the basis of 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2-2'-azino-bis-(3 ethylbenz-thiazoline-6-sulfonic acid) (ABTS+.) and ferric reducing antioxidant power (FRAP) assays. Moreover, the efficiency of methanolic, chloroformic and petroleum ether extracts and the deriving fractions from the methanolic extract was tested against human bacterial and fungal pathogenic strains using micro dilution method in 96 multiwell microtiter plate. Furthermore, leaves and stems extracts were subjected to RP-HPLC for phenolic compounds identification. Results showed that polyphenolic contents and antioxidant activities varied considerably as function of solvent polarity. Moreover, antiradical capacities against DPPH, ABTS(+.) and reducing power were maxima in methanol aerial parts extract which showed the highest polyphenol contents (134mg CE/g DW). The antimicrobial activities showed that methanolic, chloroformic and petroleum ether extracts were found to be most potent against Pseudomonas aeruginosa and Staphylococcus aureus with MIC values of 23 and 46MU.mL(-1), respectively. The fractions F(13) and F(16) have a great antifungal potential against Candida glabrata, Candida krusei and Candida parapsilesis (MIC=39MU.mL(-1)). The RP-HPLC analysis lead the identification of gallic, procatechuic and trans-cinnamic acids, methyl-4 hydroxybenzoate, n-propyl-3,4,5-trihydroxybenzoate, epicatechin, naringin and myricetin in L. guyonianum Durieu ex Boiss. leaves and stems extracts. PMID- 27393444 TI - Short Communication: Evaluation of antimicrobial activities of Harmine, Harmaline, Nicotine and their complexes. AB - Harmine, Harmaline, Nicotine and its various complexes synthesized have been characterized by physical, spectral and analytical methods and curtained for in vitro antimicrobial activity against different bacterial and fungal species at two different concentrations i.e.100MU/100ul and 200MU/100ul dose level respectively. Analysis showed that Nicotine, Zinc-Nico, Cd-Nico, Hg-Nico, Ni Nico, Cu-Nico, Co-Nico, Harmine, and Harmaline having conc. of 100ug/ 100ul had antibacterial activity on zero, 5, 4, 10, zero, 5, 7, zero, zero strain of bacteria having an average of zero (SD=0.0000), 15.2000 (SD=1.30384), 18.2500 (SD=3.30404), 20.2000 (SD=1.39841), zero (SD=0.0000), 14.6000 (SD=0.89443), 15.8571 (SD=1.34519), zero (SD=0.0000), zero (SD=0.0000) respectively. Zinc (II) chloride, Cadmium (II) Iodide, Mercury (II) chloride, Nickel (II) chloride, Copper (II) chloride, Cobalt (II) chloride, Mercury (II) chloride, Mercury (II) harmine, Mercury (II) harmaline at 100ug/100ul is valid for 7, 8, 9, 2, 7, 8, 9, 10, 8 strains of bacteria with an average of 7.1429 (SD=1.06904), 10.0000 (SD=5.01427), 14.8889 (SD=6.00925), 6.0000 (SD=0.0000), 8.5714 (SD=4.27618), 8.2500 (SD=0.88641), 14.8889 (SD=6.00925), 18.6000 (SD=2.45855), 18.5000 (SD=1.85164) respectively. The above given compounds at the conc. of 200 MU/100ul is valid for 10, 9, 10, 8, 8, 10, 10, 10, 10 strains of bacteria with an average of 8.1 (SD=1.66333), 11.7778 (SD=5.28625), 16.1000 (SD=6.36745), 6.5000 (SD=0.92582), 9.7500 (SD=4.43203), 9.9000 (SD=2.76687), 16.1000 (SD=6.36745), 22.0000 (SD=2.44949), 20.4000 (SD=2.75681) respectively. The above given compounds at conc. of 200 MU/100ul showed antibacterial action on 3, 8, 8, 10, 3, 9, 8, zero, 3 strains of bacteria with an average of 14(SD=0.000), 16.8750 (SD=1.35620), 18.2500 (SD=3.45378), 22.7000 (SD=1.82878), 14.3333 (SD=0.57735), 16.7778 (SD=1.71594), zero (SD=0.000), 12.0000 (SD=1.00000) respectively. Hence according to the average value of the zone of inhibition, maximum antibacterial activity at 100-200ug/100ul is of Hg-Nico and Mercury salt; Mercury (II) harmine having an average of 20.2000 (SD=1.39841)-22.7000 (SD=1.82878) and 18.6000 (SD=2.45855)-22.0000 (SD=2.44949). Minimum antibacterial activity at 100 200ug/100ul is Nicotine100, Nicotine-Nico100, Harmine 100,Harmaline 100, Harmine 200 having zero average (SD=0.000). PMID- 27393445 TI - Mini Review: Prevalence and correlates of vitamin D deficiency-perspectives from Pakistan. AB - Health outcomes of vitamin D deficiency (VDD) are beyond rickets, osteomalacia, osteoporosis, falls and fractures and have now touched the boundaries of CVD, diabetes and many types of cancer. Therefore, thinking of mere dependence on the sun to meet vitamin D requirements under the existing set of conditions is erroneous. Pakistan as a developing economy of South Asia and a region spanning latitude 24 degrees 35' North and longitude 61 degrees East to 78 degrees East, gravely suffers from increased VDD among pregnant women, neonates, infants, children, adolescents, adults, and the elderly people despite its abundant sunshine. Multiple indicators inflating VDD have been widely reported such as food habits, sociocultural and religious taboos, restricted sun exposure, unavailability of fortified diets, age, season, gender, lack of vitamin D supplementation, skin pigmentation and genetic factors. Strategies entailing mandatory food fortification, pragmatic implementation of vitamin D supplementation program, developing awareness on health damaging effects of the syndrome and sagacious sun exposure in tandem with global support to incline the government, program managers and consumers, need to be followed. Concerted efforts are further required to scale up the surveillance and monitoring of the magnitude of VDD by taking NGOs, industry, academia and health sector into loop to devise remedies for VDD in Pakistan. PMID- 27393446 TI - Methicillin resistant coagulase negative staphylococcus: From colonizer to a pathogen. AB - The objective of our study was to determine the frequency of methicillin resistance in coagulase negative Staphylococcus (CoNS) and to determine its in vitro antimicrobial susceptibility to various other routinely used antibiotics. It was a cross sectional study conducted at the department of Microbiology, Army Medical College, Rawalpindi, Pakistan from June 2011 to May 2012. The organisms were identified on the basis of colony morphology, Gram staining, catalase, DNAase and slide/tube coagulase tests. The organisms were considered to be methicillin resistant when the diameter of zone of inhibition was less than 25mm around 30MUg cefoxitin disc. Antibiotic sensitivity was determined using the Modified Kirby-Bauer disc diffusion method. From a total of 337 CoNS, 201 were methicillin resistant and were included in the study. All were resistant to Penicillin, followed by Erythromycin (93*1%), Ciprofloxacin (77%), Co-trimoxazole (74*8%), Gentamicin (68*3%), Clindamycin (51*06%), Tetracycline (44*6%), Fusidic acid (40%), Rifampicin (39*5%), Chloramphenicol (19*3%), Linezolid (2%), Minocycline (1*1%), and Vancomycin (0%). More than half of CoNS were methicillin resistant. Vancomycin is the only drug to which all of the MRCoNS were sensitive, with more than 98% of the isolates being sensitive to Linezolid and Minocycline. PMID- 27393447 TI - Radio sensitizing effect of aloe polysaccharide on pancreatic cancer bxpc-3 cells. AB - The roles of autophagy in pancreatic cancers are complex and may differ depending on tumor type or context. This study aimed to investigate if aloe polysaccharide can be used as a radio-sensitizing chemical to induce autophagy in pancreatic cancer cells. Pancreatic carcinoma BxPC-3 cells were divided into four groups: A control group, an aloe polysaccharide only group, a radiation only group and a radiation combined with aloe polysaccharide group (combination group). Transmission electron microscopy was used to observe ultra structural changes of autophagosomes in each cell group. The mRNA expressions of ULK1, GABARAPL1, BECN1, and BCL-2 were detected by real-time PCR. Autophagosomes or autophagolysosomes were observed in all experimental groups except the control group. Compared with the control group, ULK1 mRNA expression was up-regulated and BECN1 and BCL-2 mRNA expression were down-regulated in all groups (P<0.05); changes in expression were most obvious in the combination group (P<0.05). GABARAPL1 mRNA expression was up-regulated in the combination group (P<0.05), but had no significant changes among other groups. In brief, aloe polysaccharide induces autophagy in pancreatic carcinoma BxPC-3 cells both alone and in concert with radiation. Autophagic cell death may be one of the mechanisms producing a radiosensitizing effect. PMID- 27393448 TI - Corosolic acid suppresses the expression of inflammatory marker genes in CCL4 induced-hepatotoxic rats. AB - The aim of the study was to asses the anti-inflammatory effects of corosolic acid on the carbon tetrachloride (CCL4) toxicity in rats. Liver toxicity was induced by administered CCL4 (single dose (1:1 in liquid paraffin) orally at 1.25 ml/kg. Rats were pretreated with CRA for 7 days before made CCL(4) toxicity at 20 mg/kg BW. The mRNA levels of TNF-alpha, IL-6, iNOS, COX-2 and NF-kB were assayed by reverse transcriptase PCR analysis. The mRNA levels of proinflammatory cytokines such as TNF-alpha, IL-6, and the inflammatory markers such as iNOS, COX-2 and NF kB were significantly up regulated in CCl(4) induced rats and treatment with corosolic acid significantly reduced the expression of the above indicators. Our results suggest that the inhibition of TNF-alpha, IL-6, iNOS, COX-2 and NF-kappaB by corosolic acid, a potential candidate could possess anti-inflammatory activity besides its hepatoprotective effect in CCl4 liver toxicity in rats. PMID- 27393449 TI - Therapeutic effect of aqueous extracts of three dietary spices and their mixture on lipid metabolism and oxidative stress in a rat model of chronic alcohol consumption. AB - The protective effect of aqueous extracts of three dietary spices, garlic, (Allium sativum), ginger (Zingiber officinale) and pepper (Capsicum frutescens) singly and combined was investigated using a rat model of chronic alcohol intake. Rats were given 30% ethanol, with or without aqueous extracts of garlic, ginger, pepper or mixture of the three administered at 200mg/kg body weight by oral gavage for 28 days. Lipid profile, lipid peroxidation, oxidative and antioxidative profiles of serum, faecal, liver, kidney, heart and brain tissues of the rats were analyzed. Alcohol treatment significantly elevated liver enzymes, lipid peroxidation, depleted antioxidant system and induced histopathological changes in the liver. These alterations were markedly ameliorated by treatment with aqueous extracts of the three spices singly or mixed at 200mg/kg body weight. These results suggest that aqueous extracts of garlic, ginger, pepper or a blend of the three protects against alcohol- induced hypercholesterolemia, lipid peroxidation, oxidative stress and liver damage. PMID- 27393450 TI - A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease. AB - Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan. PMID- 27393451 TI - Polymorphisms in DNA repair genes XRCC1 and OGG1 lead to the progression of rheumatoid arthritis in Pakistani patients. AB - This study points at the elucidation of a possible association of Rheumatoid arthritis (RA) with Ser326Cys in OGG1 Arg194Trp and Arg399Gln polymorphisms of XRCC1 using a sample size of 100 patients and 100 controls from a Pakistani population. This association was determined using Random Fragment Length Polymorphism Analysis as well as the DAS scoring system. In RA, oxidative damage due to free radical production leads to destructive proliferative synovitis showing cellular transformations of synoviocytes into a tumorigenic state. XRCC1 and OGG1 genes, which are part of the DNA Break Excision Repair pathway, manifest various polymorphisms which may cause a variation in the response to inflammation by changing DNA repair potential. Our results showed a significant association between the DAS28 score values as well as the genotypic state of the RA patients. It was seen that the score was significantly higher in GG genotypes thereby corroborating the role of the polymorphism XRCC1 Arg399Gln. Using a Pearson's correlation test it was found to be <0.000003. It has been shown by the results in this research that an increased risk of DNA damage exists when the polymorphic genotypes studied, exist in a RA patient. PMID- 27393452 TI - Influence of different metals on the activation and inhibition of alpha-amylase from thermophilic Bacillus firmus KIBGE-IB28. AB - Thermophilic Bacillus firmus KIBGE-IB28 produced extracellular alpha-amylase at temperature 70 degrees C. Enzyme was partially purified by ammonium sulfate precipitation with 42.80 fold purification and specific activity of 1889.6 U/mg. Effects of various metals on enzyme activity were determined and it was found that enzyme activity boosted significantly in presence of Ca(2+), K(2+), Ba(2+), Co(2+) and Ni(2+) whereas Zn(2+), Mg(2+), Na(2+) and Cu(2+) were found inhibitory at concentration 10mM. PMID- 27393453 TI - In silico binding analysis of Withanolides with the Human GM-CSFR. AB - Experimental studies have shown that Withanolides are group of pharmacologically active compounds (steroidal lactones), immunomodulatory agents mainly present in the leaves and roots of Withania somnifera plant. The present study is about virtual screening of Withanolide compounds to check for drug likeness by Lipinski's rule five and the screened compounds are allowed to binding with the human GM-CSFR, an immunomodulatory cytokine receptor expressed on dendritic cells. The binding pocket sites, the internal energy, the hydrogen bond interactions and the interacting amino acid residues of the human GM-CSFR with Withanolides were analyzed through molecular docking method. Among the Withanolides docked with human GM-CSFR, which is responsible for DCs survival, proliferation and differentiation, Withanolide A was identified to be a lead compound by binding with alpha subunit of GM-CSFR exhibiting a maximum Dock score of 28.07 and internal binding energy of -12.8 Kcal/mol. Levamisole as a standard immunomodulatory agent has shown maximum dock score of 28.639 and internal binding energy of -1.864 Kcal/mol. Withanolide A and Levamisole was docked with similar binding site amino acid, ARG302 of GM-CSFR. In addition, Withanolide A was also binding with LEU246 of GM-CSFR, as binding aminoacids predicted from PDBSUM. PMID- 27393454 TI - Synthesis, spectral analysis and antibacterial evaluation of N'-substituted-2-(5 (3-chlorophenyl)-1,3,4-Oxadiazol-2-ylthio)acetohydrazide derivatives. AB - The biological potential of N'-substituted-2-(5-(3-chlorophenyl)-1,3,4-Oxadiazol 2-ylthio)acetohydrazide (8a-p) has been evaluated against bacterial strains of Gram-negative and Gram-positive bacteria. The multistep synthesis involved the conversion of 3-chlorobenzoic acid (1) to ethyl 3-chlorobenzoate (2), 3 chlorobenzohydrazide (3), 5-(3-chlorophenyl)-1,3,4-Oxadiazol-2-thiol (4), ethyl 2 (5-(3-chlorophenyl)-1,3,4-Oxadiazol-2-ylthio) acetate (5) and 2-(5-(3 chlorophenyl)-1,3,4-Oxadiazol-2-ylthio)acetohydrazide (6). The last step involved the reaction of 6 and aryl aldehydes, 7a-p, in methanol to synthesize the Schiff bases, 8a-p, with better yields. The structures of all the molecules were corroborated by spectral analysis. The Schiff bases were further evaluated for the antibacterial activity and found to be moderately good inhibitors of bacterial strains of Gram-bacteria. PMID- 27393455 TI - Report: Antimicrobial activity of Kalanchoe laciniata. AB - This study was conducted to identify antimicrobial potential of Kalanchoe laciniata. The plants were extracted with 30-70% aqueous-methanol and n-hexane. The antimicrobial activities were examined using agar well diffusion method against bacteria (Staphylococcus aureus, Escherichia coli) and fungi (Candidaalbicans). Results showed that E. coli were more sensitive than Staphylococcus aureus and Candida albicans. The largest zone of inhibition (52 mm) was recorded against E. coli with the n-hexane extract of Kalanchoe laciniata. PMID- 27393456 TI - Review: Comprehensive review on treatment of HIV. AB - HIV or AIDS is a major threat for humanity in the world especially in developing countries. The causative factor of the syndrome is HIV, which infects and destroys one of the cellular components of the immune system, the T cells, causing deficiency in the immunological surveillance and ultimately leading to AIDS. According to WHO, around 35 million people were living with HIV in 2013 and since the start of epidemic 39 million people have died due to AIDS. Center for disease control and prevention estimated in 2014 that 1,201,100 people aged 13 and above were suffering from HIV infection Worldwide. The most effective approach is the highly active antiretroviral therapy (HAART) containing the combined use of drugs having different mechanisms of action. However, complete eradication of HIV from the body does not occur by HAART, but it lead to long term toxicity occurs and emerges as drug resistant. Despite the recent development of various new antiretroviral compounds, there is still a need to develop need to search for new alternatives which are equally efficient and less expensive as compared to the contemporary treatment available. This review provides an overview and a summary of herbal medicines for HIV infection and summarized the efficacy and medicinal use of different plants used in the treatment of HIV infection. The objective of this review is to enlighten the recent advances in the exploration of medicinal plants used for treatment of HIV/AIDS. PMID- 27393457 TI - Nodular Peristomal Lesions. PMID- 27393458 TI - Blockade of receptor for advanced glycation end products protects against systolic overload-induced heart failure after transverse aortic constriction in mice. AB - Heart failure is the consequence of sustained, abnormal neurohormonal and mechanical stress and remains a leading cause of death worldwide. The aim of this work was to identify whether blockade of receptor for advanced glycation end products (RAGE) protected against systolic overload-induced heart failure and investigate the possible underlying mechanism. It was found that RAGE mRNA and protein expression was up-regulated in cardiac tissues from mice subjected to pressure overload by transverse aortic constriction (TAC). Importantly, inhibition of RAGE by treatment with soluble RAGE (sRAGE) or FPS-ZM1 (a high affinity RAGE-specific inhibitor) for 8 weeks attenuated cardiac remodeling (including cardiac hypertrophy and fibrosis), and dysfunction in mice exposed to TAC. Furthermore, treatment of TAC mice with sRAGE or FPS-ZM1 enhanced phosphorylation of AMPK and reduced phosphorylation of mTOR and protein expression of NFkappaB p65 in cardiac tissues. In addition, treatment of TAC mice with sRAGE or FPS-ZM1 abated oxidative stress, attenuated endoplasmic reticulum stress, and suppressed inflammation in cardiac tissues. These data demonstrated the benefits of blocking RAGE on the progression of systolic overload-induced heart failure in mice, which was possibly through modulating AMPK/mTOR and NFkappaB pathways. PMID- 27393459 TI - beta-N-oxalyl-L-alpha, beta- diaminopropionic acid induces HRE expression by inhibiting HIF-prolyl hydroxylase-2 in normoxic conditions. AB - Hypoxia inducible factor (HIF)-1alpha, a subunit of HIF transcription factor, regulates cellular response to hypoxia. In normoxic conditions, it is hydroxylated by prolyl hydroxylase (PHD)-2 and targeted for proteosomal degradation. Drugs which inhibit PHD-2 have implications in conditions arising from insufficient blood supply. beta-ODAP (beta-N- oxalyl-L-alpha, beta- diaminopropionic acid), a non-protein excitatory amino acid present in Lathyrus sativus, is an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor agonist known to activate conventional protein kinase C and stabilize HIF-1alpha under normoxic conditions. However, the mechanism of HIF-1alpha stabilization by this compound is unknown. In silico approach was used to understand the mechanism of stabilization of HIF-1alpha which revealed beta-ODAP interacts with key amino acid residues and Fe2+ at the catalytic site of PHD-2. These results were further corroborated with luciferase HRE (hypoxia response element) reporter system in HeLa cells. Different chemical modulators of PHD-2 activity and HIF-1alpha levels were included in the study for comparison. Results obtained indicate that beta ODAP inhibits PHD-2 and facilitates HIF dependent HRE expression and hence, might be helpful in conditions arising from hypoxia. PMID- 27393460 TI - Influence of sub-chronic selective 11beta-hydroxysteroid dehydrogenase 1 inhibition on the hypothalamic-pituitary-adrenal axis in female cynomolgus monkeys. AB - Inhibition of local cortisol regeneration from circulating cortisone by blocking 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been shown to ameliorate the risk factors associated with the metabolic syndrome. Chronic modulation of glucocorticoid homeostasis may result in hypothalamic-pituitary-adrenal (HPA) axis stimulation. HPA axis over-activation leading androgen excess would be undesirable in a therapeutic intervention designed to treat a chronic condition such as the metabolic syndrome. To address whether 11beta-HSD1 inhibition would lead to excess androgens, we treated female cynomolgus monkeys with a selective inhibitor, BI 135558, for 4 weeks. Continual action of the compound over the dosing period was confirmed by constant plasma exposure, and a maintained change in urinary glucocorticoid metabolites consistent with 11beta-HSD1 inhibition. No significant changes in adrenal function, as evidenced by an adrenocorticotropic hormone (ATCH) challenge, were observed. An examination of androgenic hormones revealed a slight increase in dehydroepiandrosterone sulfate (DHEA-S), while other hormones such as testosterone remained within reference values. Overall, treatment with BI 135558 in monkeys did not result in obvious over-activation of the HPA axis. PMID- 27393461 TI - Oxycodone physical dependence and its oral self-administration in C57BL/6J mice. AB - Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1 10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. PMID- 27393462 TI - [Not Available]. AB - Level of Evidence for Therapeutic Drug Monitoring of Vancomycin. Vancomycin is an antibiotic for exclusive hospital use administrated in intravenous infusion to treat systemic infections. It is mainly eliminated by kidneys and potentially nephrotoxic. Data available show that Therapeutic Drug Monitoring (TDM) of vancomycin is highly recommended. It aims to ensure efficacy and avoid resistance by maintaining trough plasma concentrations above the MIC. Secondary, vancomycine TDM may be indicated to prevent nephrotoxicity in high risk patients. TDM is often underwent at steady state (48 to 72 h after the treatment initiation) unless in case of renal impairment (24 h). While compared with intermittent administration, continuous infusion did not result in prognosis improvement; however it resulted in lower pharmacokinetic variability and better cost efficiency. Targeted trough concentrations for intermittent infusion are between 15 and 20 mg/L (up to 25-30 mg/L for GISA). In case of continuous infusion, targets are higher (25 to 40 mg/L). PMID- 27393464 TI - [Not Available]. AB - Teicoplanin is a glycopeptid antibiotic used for treatment of serious infections caused by Gram+ bacteriae. The treatment scheme corresponds to an initial loading dose followed by maintenance dose. High interindividual pharmacokinetic variability and strong relation between high through concentrations, dose and clinical success, support the need of therapeutic drug monitoring using through concentrations. Achieving through concentrations >=10-15 mg/L or >=20-40 mg/L, regarding the measurement method and the infection severity, is recommended to increase clinical success rate. The level of proof of therapeutic drug monitoring is evaluated: "necessary". PMID- 27393463 TI - [Not Available]. AB - Aminoglycosides are major antibiotics indicated for the treatment of infection with gram-negative bacilli. They are characterized by high clinical effectiveness but their main drawback is the occurrence of toxicity in a significant number of patients. Pharmacokinetic parameters of aminoglycosides exhibit wide inter individual variability and the relationships between concentration and effect have been clearly demonstrated. Consistent studies have demonstrated that therapeutic drug monitoring (TDM) of aminoglycosides administered in multiple daily doses was cost-effective in maximising antibiotic efficacy and/or reducing incidence of toxicity. Therefore TDM of aminoglycosides should be considered "essential". Level of evidence for TDM of aminoglycosides administered once daily is not so clearly demonstrated however it should be highly recommended. PMID- 27393465 TI - [Not Available]. AB - Mycophenolic acid (MPA) is more and more used to prevent GVHD (Graft Versus Host Disease) during hematopoietic stem cell transplantation with reduce-intensity conditioning. If several facts argue in favor of therapeutic drug monitoring, the used pharmacokinetic parameter is to be defined. Especially, the choice between total or ultrafilterable MPA is still under debate even if therapeutic drug monitoring seems to be more practicable with total MPA. The role of other factors implied in GVHD occurrence are also to be assessed in studies which aim at assessing therapeutic drug monitoring of MPA in such situation. For theses reasons, the level evidence of MPA as GVHD prophylaxis during hematopoietic stem cell transplantation with reduce-intensity conditioning is potentially useful. PMID- 27393466 TI - [Not Available]. AB - Everolimus has proven efficacy for prevention of rejection in adult de novo renal and cardiac transplant recipient in combination with ciclosporine and corticosteroids. Therapeutic drug monitoring (TDM) with target trough concentration (C0) value from 3 to 8 MUg/L has been proposed. Through a systematic review of the literature, this work explored a level of recommendation for this TDM. Everolimus exhibits both wide interindividual pharmacokinetic variability and poor relationship between dose and exposure. A good relationship has been reported between C0 values and global exposure to the drug (i.e. AUC). Although C0 > 3 MUg/L has been associated with a decreased incidence of rejection, the upper limit of 8 MUg/L has never been formally validated. No clinical trial testing other exposure indices or comparing efficacy and/or toxicity of everolimus therapy with and without TDM has been published so far. Consequently the level of recommendation for everolimus monitoring is "recommended". PMID- 27393467 TI - Proteolytic processing of Neuregulin-1. AB - Neuregulin-1 (NRG1), known also as heregulin, acetylcholine receptor inducing activity (ARIA), glial growth factor (GGF), or sensory and motor neuron derived factor (SMDF), is a key factor for many developmental processes and in adult brain. All known splice variants contain an epidermal growth factor (EGF)-like domain, which is mediating signaling via receptors of the ErbB family. In particular, NRG1 acts as an essential signaling molecule expressed on the axonal surface, where it signals to Schwann cells throughout development and regulates the thickness of the myelin sheath. NRG1 is required also by other cell types in the nervous system, for instance as an axonal signal released by proprioceptive afferents to induce development of the muscle spindle, and it controls aspects of cortical interneuron development as well as the formation of thalamo-cortical projections. The precursor protein of NRG1 can be activated and released from the membrane through limited proteolysis by the beta-Secretase (beta-site amyloid precursor protein cleaving enzyme 1, BACE1) which was first identified through its function as the rate limiting enzyme of amyloid-beta-peptide (Abeta) production. Abeta is the major component of amyloid plaques in Alzheimer's disease (AD). Due to the hairpin nature of NRG1 type III two membrane-bound stubs with a type 1 and a type 2 orientation are generated by an initial proteolytic cleavage and successive release of the EGF-like domain either by dual cleavage by BACE1 or by ADAM17 (a disintegrin and metalloprotease) which is also called TACE (Tumor Necrosis Factor-alpha-converting enzyme). The cleavages activate NRG1 to allow juxtacrine or paracrine signaling. The type 1 oriented stub is further cleaved by gamma-secretase in the transmembrane domain with a putative role in intracellular domain (ICD) signaling, while the type II oriented stub is cleaved by signal peptidase like proteases (SPPLs). Neuregulin-1 was identified as a major physiological substrate of BACE1 during early postnatal development when similarities in BACE1 KO mice and NRG1 heterozygous mice were discovered. Both display severe hypomyelination of peripheral nerves. Later it was shown with genetic and pharmacological evidence that the developmental effect of type I NRG1 on the formation and the maintenance of muscle spindles is BACE1 dependent. Thus, NRG1 functions in PNS and CNS are likely to set limits to an Alzheimer disease therapy with relatively strong BACE1 inhibition. PMID- 27393468 TI - Cloning-free genome engineering in Sinorhizobium meliloti advances applications of Cre/loxP site-specific recombination. AB - The soil-dwelling alpha-proteobacterium Sinorhizobium meliloti serves as model for studies of symbiotic nitrogen fixation, a highly important process in sustainable agriculture. Here, we report advancements of the genetic toolbox accelerating genome editing in S. meliloti. The hsdMSR operon encodes a type-I restriction-modification (R-M) system. Transformation of S. meliloti is counteracted by the restriction endonuclease HsdR degrading DNA which lacks the appropriate methylation pattern. We provide a stable S. meliloti hsdR deletion mutant showing enhanced transformation with Escherichia coli-derived plasmid DNA and demonstrate that using an E. coli plasmid donor, expressing S. meliloti methyl transferase genes, is an alternative strategy of increasing the transformation efficiency of S. meliloti. Furthermore, we devise a novel cloning free genome editing (CFGE) method for S. meliloti, Agrobacterium tumefaciens and Xanthomonas campestris, and demonstrate the applicability of this method for intricate applications of the Cre/lox recombination system in S. meliloti. An enhanced Cre/lox system, allowing for serial deletions of large genomic regions, was established. An assay of lox spacer mutants identified a set of lox sites mediating specific recombination. The availability of several non-promiscuous Cre recognition sites enables simultaneous specific Cre/lox recombination events. CFGE combined with Cre/lox recombination is put forward as powerful approach for targeted genome editing, involving serial steps of manipulation to expedite the genetic accessibility of S. meliloti as chassis. PMID- 27393469 TI - Special Collection: Cell-Based Therapy for Bone Regeneration. PMID- 27393470 TI - Extent of Internal Limiting Membrane Peeling and its Impact on Macular Hole Surgery Outcomes: A Randomized Trial. AB - PURPOSE: To identify whether and how outcomes of macular hole (MH) surgery are influenced by the extent of internal limiting membrane (ILM) peeling. DESIGN: Randomized clinical trial. METHODS: This study involved 65 eyes from 65 patients who underwent surgery for idiopathic MH. ILM was peeled with a radius of either 0.75 disc diameter (small-extent group, SEG) or 1.5 disc diameter (large-extent group, LEG), according to the randomization. Anatomic success, visual acuity, and metamorphopsia score (M-score) were measured at 2- and 6-month postoperative visits. The distance between the foveal center and the parafoveal edge of the outer plexiform layer on optical coherence tomography was measured in 4 directions, and further distance increases in certain directions were defined as asymmetric elongation of foveal tissue. RESULTS: Complete closure of the MH was observed after initial operation in 97.0% of eyes in both groups. The mean visual improvement at 6 months after surgery was 20.4 +/- 12.8 and 19.1 +/- 10.8 ETDRS letters in SEG and LEG, respectively (P = .452). The mean amount of improvement in M-score was 0.26 +/- 0.55 in SEG and 0.50 +/- 0.53 in LEG (P = .039). There was a difference in the mean degree of asymmetric elongation between the 2 groups (22.5% +/- 10.8% in SEG vs 13.4% +/- 5.8% in LEG, P = .001). And there was inverse correlation between the mean degree of asymmetric elongation and the amount of improvement in M-score at 6 months postoperatively (P < .001). CONCLUSION: Larger extent of ILM peeling during MH surgery is beneficial with respect to reduction of metamorphopsia, alleviating asymmetric elongation of foveal tissue. PMID- 27393471 TI - [Not Available]. AB - Direct current cardioversion is effective in arrhythmias' termination. Few is known about its use in our practice. This work aims to report its outcomes over a ten-year period in Abidjan. METHOD: One thousand, three hundred and ninety one charts of arrhythmic patients were reviewed. RESULTS: Cardioversion was attempted in 102 patients. One hundred and eighty one shocks were delivered with a mean energy of 262, 1 joules. Success occurred in 84 patients (82,3%). Cardioversion failed in 18 patients mostly in atrial fibrillation. Eight serious complications (7,8%) occurred including 1 sinus node dysfunction, 1 pulmonary oedema, 1 metrorrhagia, 2 stroke, 1 pulmonary embolism. Two patients with ventricular tachycardia died of end-stage heart failure and aftermath of a mitral valve surgery. CONCLUSION: Direct current cardioversion is effective and safe in our practice. Complications are predominantly due to the medical environment such as antiarrhythmic drugs use or clinical conditions. PMID- 27393472 TI - [Not Available]. AB - A tripartite group, entitled " CRI " (for Cercle de reflexion sur l'imputabilite), involving French pharmacovigilance staff from the French network of the Regional centers of pharmacovigilance, from pharmaceutical companies, and from French Health Authorities (Agence francaise de securite sanitaire des produits de sante) has worked to update the French drug reaction assessment method. Following assessment of strengths and weaknesses of the previous method, several points for improvement are proposed : a more precise wording and a more discriminating scale for some of the chronological and semiological criteria, a wider distribution of the intrinsic score from 5 to 7 levels, a new bibliographic scale for differentiating expected and unexpected adverse drug reactions, and a new informativness scale. This updated method would lead to a more relevant assessment of relationship between a drug and the occurrence of an adverse reaction. Furthermore, this method is a teaching tool to assess the level of relationship between a drug and the occurrence of an adverse reaction. PMID- 27393473 TI - Assessment of Lymph Node Ratio to Replace the pN Categories System of Classification of the TNM System in Esophageal Squamous Cell Carcinoma. AB - INTRODUCTION: The seventh edition of the TNM staging system for esophageal cancer outlined by the American Joint Committee on Cancer (AJCC) defines the N classification on the basis of the number of metastatic lymph nodes. However, this classification is dependent on the actual number of examined lymph nodes. Here in this study, we have focused on revising this N classification system with the metastatic lymph nodes ratio (LNR) and also assessing whether this modification to the current AJCC staging system can better define the prognostic characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 916 patients with ESCC who underwent curative resection. Prognostic performance of two staging systems was compared using the Akaike information criterion value and receiver operating characteristics curve. In addition, decision curve analysis evaluated the clinical practical usefulness of the prediction models by quantifying their net benefits. RESULTS: The univariate and multivariate Cox regression analyses indicated that LNR was an independent risk factor for overall survival. The modified staging system based on LNR had better discriminatory ability, monotonicity, homogeneity, and stratification than the TNM staging system in determining the prognosis of patients with ESCC. However, the decision curves analysis suggested that the modified staging based on LNR has poor clinical practical value over the AJCC TNM staging system. CONCLUSIONS: LNR can supplement the pN categorization system for more effective evaluation of prognosis. But the modified staging system based on LNR has a poor clinical practical value for patients with ESCC compared with the current TNM system and is not superior to AJCC pN staging for ESCC. PMID- 27393474 TI - Outcome after PORT in ypN2 or R1/R2 versus no PORT in ypN0 Stage III-N2 NSCLC after Induction Chemotherapy and Resection. AB - INTRODUCTION: We investigated patients with contemporarily staged and treated stage III-N2 NSCLC treated with induction chemotherapy and surgery with or without postoperative radiotherapy (PORT). We focused on survival and toxicity and investigated what additional PORT may offer in patients with ypN2 status or incomplete resection. METHODS: We identified 161 patients with pathologically proven, resectable stage III-N2 NSCLC from our prospective database who were treated between 1998 and 2012. Of these patients, 150 without progressive disease after chemotherapy underwent resection. Patients with ypN2 status or R1/2 resection received three-dimensional PORT (n = 70) to a dose of 50 to 66 Gy in 2 Gy fractions. RESULTS: The mean follow-up time was 49 months. The 5-year overall survival (OS) rate was 35.1% in intention-to-treat analysis; relapse-free survival was 31.8%, the cumulative local recurrence (LR) rate was 50.9%, and the distant metastasis rate was 63.4%. The 5-year OS, relapse-free survival, and cumulative LR and distant metastasis rates were 32.0%, 32.9%, 47.0%, and 63.9% in the PORT group versus 38.1%, 30.7%, 54.1%, and 63.2% in the non-PORT group. These results were not significantly different, even though patients in the PORT group had worse prognostic features. Cardiac toxicity was higher in the non-PORT group (p = 0.02), but pulmonary toxicity was similar (p = 0.15). There was no difference between the two groups regarding dyspnea (p = 0.32), cough (p = 0.37), forced expiratory volume in 1 second (p = 0.30), and diffusing capacity of the lung for carbon monoxide (p = 0.61). CONCLUSIONS: A similar outcome (OS, LR, and toxicity) was seen in both patient groups (PORT versus non-PORT group). Despite the limitations of this retrospective study, PORT can be both effective and safe for patients with stage III-N2 NSCLC with an R1/R2 resection or yN2 after induction chemotherapy and surgery. PMID- 27393475 TI - Erratum to Reversal of Transjugular Intrahepatic Portosystemic Shunt (TIPS) Induced Hepatic Encephalopathy Using a Strictured Self-Expanding Covered Stent. PMID- 27393476 TI - Erratum to Endovascular Placement of an Extraluminal Femoropopliteal Bypass Graft in Human Cadavers. PMID- 27393478 TI - Characteristics of Hospitalizations for the Glenn Procedure in Those With Isomerism Compared to Those Without. AB - Isomerism, also known as heterotaxy, is a unique clinical entity in which there are mirror imaged findings in the thoracic. In the abdomen, the arrangement of organs can be random. The anatomic findings also have functional consequences. Isomerism has been known to increase morbidity and mortality in those with functionally univentricular hearts. The aim of this study was to determine the impact of isomerism on the Glenn hospitalization. Data from the 1997 to 2012 Kids' Inpatient Database were utilized for this cross-sectional study. Admissions during which a Glenn procedure was done were identified. Next, these admissions were separated into those with and without isomerism. Admission characteristics were then compared in a univariate fashion as well as by regression analysis. Length of hospitalization, cost of hospitalization, extracorporeal membrane oxygenation, and inpatient mortality were the outcomes of interest. A total of 4959 admissions with a Glenn procedure were identified. Of these, 450 were associated with isomerism. The median age at which the Glenn procedure was done was 10 and 13 months in those without and with isomerism, respectively. Neither univariate nor regression analysis demonstrated any significant difference in length of hospitalization, cost of hospitalization, need for extracorporeal membrane oxygenation, and inpatient mortality between those with and without isomerism. Isomerism does not impact the characteristics of the Glenn hospitalization. Those with isomerism did tend to be older when they underwent the Glenn procedure. PMID- 27393479 TI - Novel Percutaneous Coronary Intervention Techniques for Revascularizing Chronically Occluded Giant Coronary Aneurysms in a Patient with Kawasaki Disease. AB - Kawasaki disease is a self-limiting vasculitis presenting in childhood that can lead to aneurysms of the coronary arteries. Patients who develop giant coronary aneurysms have a high incidence of coronary stenoses and occlusions resulting in myocardial ischemia. The mainstay of treatment for these lesions is surgical bypass due to complex coronary anatomy and a high rate of chronic total occlusions precluding traditional percutaneous coronary intervention techniques. We report the first successful percutaneous revascularization of two chronically occluded giant coronary aneurysms using the Hybrid Interventional Strategy for approaching chronic total occlusions. Both antegrade and retrograde dissection reentry techniques were employed to fully revascularize two major epicardial arteries. Despite procedural success, longer-term vessel patency was not maintained following stent deployment highlighting the difficulty in maintaining durable results with percutaneous coronary intervention in this patient population. PMID- 27393481 TI - Lipophilicity in Drug Development: Too Much or Not Enough? AB - A round table discussion was held during the AAPS Annual Meeting on October 27, 2015, with the somewhat provocative topic of whether we need more or less lipophilic compounds in drug development. The session was attended by more than 250 participants, and the feedback was very positive as this round table became a forum for the exchange of ideas from scientists within the academia and industry. Most importantly, the discussion highlighted the difference in approaches to compound selection and development strategies in various companies and organizations. As moderators of this session, we are writing this report to highlight the points and counterpoints made at the session and to bring the importance of the dialogue and debate to the forefront of discussions on how to select the best drug development candidates to enable efficient delivery and, hence, treatment of diseases. PMID- 27393480 TI - In Vivo Exposure of Kaempferol Is Driven by Phase II Metabolic Enzymes and Efflux Transporters. AB - Kaempferol is a well-known flavonoid; however, it lacks extensive pharmacokinetic studies. Phase II metabolic enzymes and efflux transporters play an important role in the disposition of flavonoids. This study aimed to investigate the mechanism by which phase II metabolic enzymes and efflux transporters determine the in vivo exposure of kaempferol. Pharmacokinetic analysis in Sprague-Dawley rats revealed that kaempferol was mostly biotransformed to conjugates, namely, kaempferol-3-glucuronide (K-3-G), kaempferol-7-glucuronide (K-7-G), and kaempferol-7-sulfate, in plasma. K-3-G represented the major metabolite. Compared with that in wild-type mice, pharmacokinetics in knockout FVB mice demonstrated that the absence of multidrug resistance protein 2 (MRP2) and breast cancer resistance protein (BCRP) significantly increased the area under the curve (AUC) of the conjugates. The lack of MRP1 resulted in a much lower AUC of the conjugates. Intestinal perfusion in rats revealed that the glucuronide conjugates were mainly excreted in the small intestine, but 7-sulfate was mainly excreted in the colon. In Caco-2 monolayers, K-7-G efflux toward the apical (AP) side was significantly higher than K-3-G efflux. In contrast, K-3-G efflux toward the basolateral (BL) side was significantly higher than K-7-G efflux. The BL-to-AP efflux was significantly reduced in the presence of the MRP2 inhibitor LTC4. The AP-to-BL efflux was significantly decreased in the presence of the BL-side MRPs inhibitor MK571. The BCRP inhibitor Ko143 decreased the glucuronide conjugate efflux. Therefore, kaempferol is mainly exposed as K-3-G in vivo, which is driven by phase II metabolic enzymes and efflux transporters (i.e., BCRP and MRPs). PMID- 27393482 TI - Capsule Commentary on Callon et al., Assessing Problematic Substance Use in HIV Care: Which Questions Elicit Accurate Patient Disclosures? PMID- 27393483 TI - Capsule Commentary on Mehta et al. Race/Ethnicity and Adoption of a Population Health Management Approach to Colorectal Cancer Screening in a Community-Based Healthcare System. PMID- 27393484 TI - An Abscess of Urachal Remnant. PMID- 27393485 TI - How Can We Improve the Efficiency of Specialty Care? PMID- 27393486 TI - Barriers to Post-Acute Care for Patients on Opioid Agonist Therapy; An Example of Systematic Stigmatization of Addiction. PMID- 27393487 TI - Computational functional group mapping for drug discovery. AB - Computational functional group mapping (cFGM) is emerging as a high-impact complement to existing widely used experimental and computational structure-based drug discovery methods. cFGM provides comprehensive atomic-resolution 3D maps of the affinity of functional groups that can constitute drug-like molecules for a given target, typically a protein. These 3D maps can be intuitively and interactively visualized by medicinal chemists to rapidly design synthetically accessible ligands. Given that the maps can inform selection of functional groups for affinity, specificity, and pharmacokinetic properties, they are of utility for both the optimization of existing drug candidates and creating novel ones. Here, I review recent advances in cFGM with emphasis on the unique information content in the approach that offers the potential of broadly facilitating structure-based ligand design. PMID- 27393488 TI - Applying the best of oncology drug development paradigms to the non-malignant space. AB - With 80-90% of drugs entering the clinic not meeting regulatory approval (a high cost of failure), there is a major need for innovation in the clinical development space. Features of the new era of practice-changing innovation in oncology have included novel clinical trial designs incorporating multiple new molecular entities and/or multiple patient types, patient selection strategies (which allow detection of early signs of efficacy), and use of surrogate endpoints to achieve speedy regulatory approval. Disease areas beyond oncology could benefit from the application of specific aspects of these approaches. Here, we describe several such potential adaptations of the approaches, with scenarios and prerequisites, which could help reduce the costs of, and accelerate, clinical drug development with confidence. PMID- 27393489 TI - Misuse of anaesthetic gases. PMID- 27393490 TI - Binary toxin and its clinical importance in Clostridium difficile infection, Belgium. AB - Binary toxin-producing Clostridium difficile strains such as ribotypes 027 and 078 have been associated with increased Clostridium difficile infection (CDI) severity. Our objective was to investigate the association between presence of the binary toxin gene and CDI severity and recurrence. We performed a laboratory based retrospective study including patients between January 2013 and March 2015 whose fecal samples were analyzed by polymerase chain reaction (PCR) for the presence of the genes for toxin B and binary toxin and a deletion in the tcdC gene, specific for ribotype 027. Clinical and epidemiological characteristics were compared between 33 binary toxin-positive CDI patients and 33 binary toxin negative CDI patients. Subsequently, the characteristics of 66 CDI patients were compared to those of 66 diarrhea patients who were carriers of non-toxigenic C. difficile strains. Fifty-nine of 1034 (5.7 %) fecal samples analyzed by PCR were binary toxin-positive, belonging to 33 different patients. No samples were positive for ribotype 027. Binary toxin-positive CDI patients did not differ from binary toxin-negative CDI patients in terms of disease recurrence, morbidity, or mortality, except for a higher peripheral leukocytosis in the binary toxin positive group (16.30 * 109/L vs. 11.65 * 109/L; p = 0.02). The second part of our study showed that CDI patients had more severe disease, but not a higher 30 day mortality rate than diarrhea patients with a non-toxicogenic C. difficile strain. In our setting with a low prevalence of ribotype 027, the presence of the binary toxin gene is not associated with poor outcome. PMID- 27393491 TI - Is it possible to prevent recurrent vulvovaginitis? The role of Lactobacillus plantarum I1001 (CECT7504). AB - The purpose of this study was to prospectively evaluate the impact of the use of L. plantarum I1001 applied vaginally on Vulvovaginal Candidiasis (VVC) time-until recurrence after treatment with single-dose vaginal clotrimazole. This was a clinical open-label, prospective study of two non-randomized parallel cohorts with symptomatic acute VVC: (1) 33 sexually active women 18-50 years old, prescribed a standard single-dose 500 mg vaginal tablet of clotrimazole followed by vaginal tablets with L. plantarum I1001 as adjuvant therapy, and (2) 22 women of similar characteristics but prescribed single-dose clotrimazole only. Use of the probiotic and factors that might influence recurrence risk (age, recurrent VVC within previous year, antibiotic prior to study enrolment, diaphragm or IUD contraception, among others) were included in a multivariate Cox regression model to adjust for potential between-cohort differences. Probiotic use was associated with a three-fold reduction in the adjusted risk of recurrence (HR [95 %CI]: 0.30 [0.10-0.91]; P = 0.033). Adjusted free-survival recurrence was 72.83 % and 34.88 % for the probiotic and control groups, respectively. A higher cumulative recurrence was also observed in cases with use of antibiotics prior to enrolment (HR [95 %CI]: 10.46 [2.18-50.12]; P = 0.003). Similar findings were found at six months after azole treatment in women with RVVC. Overall, good compliance with the probiotic was reported for 91.3 % of women. The study suggests that follow-up therapy with vaginal tablets with L. plantarum I1001 could increase the effectiveness of single-dose 500 mg clotrimazole at preventing recurrence of VVC, an effect that was also observed in women with recurrent vulvovaginal candidiasis (RVVC) after six months of azole treatment. PMID- 27393492 TI - Plasma proteomics for the assessment of acute renal transplant rejection. AB - Renal transplant is the best treatment for patients with chronical kidney disease however acute graft rejection is the major impediment to success in renal transplantation leading to loss of the organ the first year after transplantation. The aim of this study was to identify plasma proteins that may be early biomarkers of acute rejection of renal allograft, developing a diagnostic model that avoids the loss of the transplanted organ. Shotgun proteomics (LC-MS/MS) method was used to analyze a set of thirty-one plasma samples, including 06 from patients with acute graft rejection after transplantation (rejection group/Rej-group) and twenty-five from renal transplant patients with stable renal graft function (control group/Ct-group). As results nineteen proteins were upregulated in the rejection group compared to the control group, and two proteins were downregulated; and three were present exclusively in the rejection group. After analysis, we selected four proteins that were related to the acute phase response and that were strongly associated with each other: they are alpha-1 antitrypsin (A1AT), alpha-2 antiplasmin (A2AP), serum amyloid A (SAA) and apolipoprotein CIII (APOC3). We think that simultaneous monitoring of SAA and APOC3 can provide insights into a broad profile of signaling proteins and is highly valuable for the early detection of a possible acute renal graft rejection. STATEMENT OF SIGNIFICANCE OF THE STUDY: In this study we did plasma shotgun patients with and without acute rejection of renal allograft. In a clinical setting an acute rejection is typically suspected upon an increase in plasma creatinine and renal biopsy. But these methods are late and unspecific; sometimes the rejection process is already advanced when there is an increase in serum creatinine. Therefore, it is necessary to find proteins that can predict the allograft rejection process. In our study were able to identify changes in the concentration of plasma protein belonging to a network of protein interaction processes the acute phase response. We believe, therefore, that development of a routine diagnosis of these proteins can detect early acute rejection of renal allograft process, thus preventing its loss. PMID- 27393493 TI - [Not Available]. AB - The purpose of this study was to identify the characteristics of psychotropic drug use and abuse by drugs addicts. The results are based on data from OPPIDUM (Observation des Produits Psychotropes Illicites ou Detournes de leur Utilisation Medicamenteuse), an annual survey primarily concerned with the consumption of licit and illicit drugs. The study involved 3373 patients recruited during october 2004 from 109 health centers. The main trends observed were an increasing interest for opioid maintenance treatment by methadone versus buprenorphine high dosage (patients treated by methadone are mainly represented for the first year of the OPPIDUM program), some changes in illicit drugs uses (increase in sniff and decrease in intravenous injection) and changes in the grading of the most consumpted benzodiazepines (decrease in flunitrazepam consumption and increase in clonazepam consumption). Main warnings concern the buprenorphine illicit use leading to firstly dependence and the illicit use of some benzodiazepines, especially clonazepam. PMID- 27393494 TI - Mast cells as effector cells of innate immunity and regulators of adaptive immunity. AB - Mast cells are widely distributed in human organs and tissues and they are particularly abundant at major body interfaces with the external environment such as the skin, the lung and the gastrointestinal tract. Moreover, mast cells are located around blood vessels and are highly represented within central and peripheral lymphoid organs. The strategic distribution of mast cells closely reflects the primary role of these cells in providing first-line defense against environmental dangers, in regulating local and systemic inflammatory reactions and in shaping innate and adaptive immune responses. Human mast cells have pleiotropic and multivalent functions that make them highly versatile cells able to rapidly adapt responses to microenvironmental changes. They express a wide variety of surface receptors including immunoglobulin receptors, pathogen associated molecular pattern receptors and danger signal receptors. The abundance of these receptors makes mast cells unique and effective surveillance cells able to detect promptly aggression by viral, bacterial and parasitic agents. In addition, mast cells express multiple receptors for cytokines and chemokines that confer them the capacity of being recruited and activated at sites of inflammation. Once activated by immunological or nonimmunological stimuli mast cells secrete a wide spectrum of preformed (early) and de novo synthesized (late) mediators. Preformed mediators are stored within granules and are rapidly released in the extracellular environment to provide a fast vascular response that promotes inflammation and local recruitment of other innate immunity cells such as neutrophils, eosinophils, basophils and monocyte/macrophages. Later on, delayed release of multiple cytokines and chemokines from mast cells further induce modulation of cells of adaptive immunity and regulates tissue injury and, eventually, resolution of inflammation. Finally, mast cells express several costimulatory and inhibitory surface molecules that can finely tune activities of T cells, B cells and regulatory cells by cognate interactions within lymphoid organs. The multivalent capacity to recognize and to react to internal and external dangers together with their ability to cross-talk with other immunocompetent cells make mast cells a unique effector cell of innate responses and a main bridge between innate and adaptive immunity. PMID- 27393495 TI - Mast cells in human digestive tube in normal and pathological conditions. AB - Mast cells (MCs) are localized in connective tissues and are more numerous near the boundaries between the external environment and the internal milieu including the skin, the respiratory tract, the gastrointestinal tract and the conjunctiva. In the gastrointestinal tract, MCs represent 1-5% of mononuclear cells in the lamina propria of the mucosa and in the submucosa, and they are also found inside the epithelium and deep in the muscle and serosal layers. The gastrointestinal MCs perform their biological functions, releasing mediators, as amines (histamine, serotonin), cytokines, proteases, lipid mediators (leukotrienes, prostaglandins), and heparin. MCs are involved in the pathogenesis of different inflammatory conditions and tumors of the gastrointestinal tract. The use of MCs' tryptase inhibitors or c-KitR tyrosine kinase inhibitors could represent a potential anti-MC therapeutic approach in all the inflammatory and tumor pathological conditions of the digestive tube in which MCs are involved. PMID- 27393496 TI - Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles. AB - Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress. Ankrd2 has also been detected in the heart, in ventricular cardiomyocytes and in the intercalated disks (ICDs). The main objective of this study was to distinguish between the Ankrd2 isoforms and to determine the contribution of each one to the general profile of Ankrd2 expression in striated muscles. We demonstrated that the known expression and localization pattern of Ankrd2 in striated muscle can be attributed to the isoform of 333 aa which is dominant in both tissues, while the designated cardiac and canonical isoform of 360 aa was less expressed in both tissues. The 360 aa isoform has a distinct nuclear localization in human skeletal muscle, as well as in primary myoblasts and myotubes. In contrast to the isoform of 333 aa, it was not preferentially expressed in slow fibers and not localized to the ICDs of human cardiomyocytes. Regulation of the expression of both isoforms is achieved at the transcriptional level. Our results set the stage for investigation of the specific functions and interactions of the Ankrd2 isoforms in healthy and diseased human striated muscles. PMID- 27393497 TI - Combined arthroscopic tenodesis of the long head of biceps and rotator cuff repair in antero-superior cuff tears. AB - PURPOSE AND HYPOTHESIS: This study evaluates the functional and cosmetic results following fixation of the long head of the biceps (LHB) tendon at the antero medial footprint anchor of a rotator cuff reconstruction, using the "lasso-loop" technique. METHODS: 39 patients with a mean age of 62 years with a rotator cuff tear and associated lesion of the LHB tendon were included in this study. Besides rotator cuff repair in an arthroscopic anchor technique, all patients received additional LHB tenodeses using the lasso-loop technique. Clinical follow-up consisted of the Constant score (CS), LHB score, DASH score, and WORC index. Relevant sub-items, such as elbow flexion strength and cosmesis, were compared to the contralateral arm. RESULTS: At an average follow-up of 22 months (11-39 months), the CS resulted in an average of 81 points. The biceps-specific LHB score showed a mean value of 89 points. The analysis of the DASH score showed an average of 16.9 points and the analysis of the WORC index showed an average result of 79.7 %. Distalization of the biceps muscle was objectively in three cases (7.7 %) (as observed by the examiner) and subjectively in one of those cases (as noted by the patient). There was a loss in elbow flexion strength compared to the contralateral side; however, this loss was not statistically significant and not associated with clinical apparent re-tear or insufficiency of the tenodesis. DISCUSSION: The arthroscopic lasso-loop tenodesis of the LHB tendon is a time and cost-efficient technique. No additional anchor is needed when included in the rotator cuff repair. Functional and cosmetical results as well as results from the biceps-specific LHB score were good to excellent. The loss in elbow flexion strength is most likely associated with concomitant rotator cuff lesion. CONCLUSION: The lasso-loop fixation technique of the LHB tendon using the antero-medial footprint anchor in rotator cuff tears is a reliable and cost-efficient procedure. LEVEL OF EVIDENCE: III. PMID- 27393498 TI - Effects of a novel foot-ankle orthosis in the non-operative treatment of unicompartmental knee osteoarthritis. AB - INTRODUCTION: Unloader braces are non-surgical treatment options for patients with unicompartmental knee osteoarthritis (OA). However, many patients do not adhere to brace treatment because of complications related to discomfort and poor fit. An alternative to knee bracing is an ankle-foot orthosis (AFO) with a lever arm that presses the lower leg into valgus or varus. The aim of this study is to evaluate the clinical benefits of this AFO for patients with unicompartmental knee OA. MATERIALS AND METHODS: Twenty-three patients with knee OA were enrolled in this observational study. The primary clinical outcome measure was the Western Ontario and McMasters Universities Arthritis Index (WOMAC) total score. Secondary outcome measures included WOMAC subscores, visual analogue pain scale, activity restriction and complication rate. Clinical scores were collected at start and 3, 6, 9, and 12 months after enrollment. Statistical evaluation was performed using the Student's t test. RESULTS: Of the patients enrolled, 83 % suffered from medial compartment OA. Most patients had Grade II OA according to the Kellgren and Lawrence classification. WOMAC total score, both subscores and visual analogue pain scale were significantly improved over time. Patients also noted a reduction in restrictions to activities of daily living and sport-related activities while using the AFO. No patients discontinued orthosis use because of adverse effects. Two types of complications were noted: discomfort or light pressure sores around the ankle (7 patients), and wear and tear of the shoe in which the AFO was worn (14 patients). CONCLUSIONS: This observational study suggests that this AFO is effective at significantly reducing pain and stiffness as well as improving the physical function of patients with mild to moderate unicompartmental osteoarthritis of the knee. PMID- 27393499 TI - Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer. AB - OBJECTIVES: The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight. MATERIALS AND METHODS: This multicenter, randomized, placebo controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas((r)) test, KRAS mutation by cobas((r))KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate. RESULTS: Overall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations (p<0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR=0.32, 95% confidence intervals [CI]: 0.14-0.69, p=0.0024). CONCLUSION: Activating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation. PMID- 27393500 TI - Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study. AB - OBJECTIVES: Second-generation ALK inhibitors are recently available for ALK+ non small cell lung cancer (NSCLC) patients previously treated with crizotinib. This study described characteristics, treatment sequencing, and outcomes among locally advanced/metastatic crizotinib-experienced ALK+ NSCLC patients. MATERIALS AND METHODS: From July 2014 to June 2015, a retrospective patient chart review was conducted among physicians from the US, EU, Korea, and Latin America. Participating clinicians identified their ALK+ NSCLC patients who received crizotinib and reported on their clinical characteristics, treatments, and survival using a pre-defined case report form. Kaplan-Meier analyses were used to describe overall survival (OS) and clinician-defined progression-free survival (PFS). RESULTS: Participating clinicians reviewed charts of 158 ALK+ NSCLC patients treated with crizotinib during the study period. Crizotinib was most commonly received in the second-line setting (41% of patients), though this varied across geographical regions. Roughly half (53%) of the patients who discontinued crizotinib received further antineoplastic therapy; second generation ALK inhibitors (44%) and chemotherapy (42%) regimens were used most frequently. Following crizotinib discontinuation, median OS was 8.2 months. Among patients who did not initiate a second-generation ALK inhibitor following crizotinib, median OS was 4.9 months; among those who did, median OS was not reached. Among patients who received chemotherapy immediately following crizotinib discontinuation, time to clinician-defined PFS from post-crizotinib chemotherapy initiation was 3.6 months. CONCLUSION: Following crizotinib discontinuation, many patients received no further antineoplastic therapy, and OS was poor among patients who did not receive a second-generation ALK inhibitor. Recently available second-generation ALK inhibitors may provide important treatment options for ALK+ NSCLC patients. PMID- 27393501 TI - Predictive impact for postoperative recurrence using the preoperative prognostic nutritional index in pathological stage I non-small cell lung cancer. AB - BACKGROUND: The most effective treatment for early-stage non-small cell lung cancer (NSCLC) is surgical resection. Nevertheless, up to 20% of patients, even those with stage I NSCLC, relapse after surgery and die. The prognostic nutritional index (PNI) is used to assess immunonutritional conditions or is a predictor of postoperative recurrence in patients with digestive malignancies. However, the usefulness of the PNI for lung cancer is still unknown. We retrospectively analyzed clinicopathological features of stage I NSCLC patients to identify predictors of recurrence and to investigate effects of preoperative PNI levels. METHODS: We selected 141 consecutive stage I NSCLC patients who were treated from August 2005 to August 2010. We measured their preoperative PNI levels in uni- and multivariate Cox regression analyses of recurrence-free survival. RESULTS: A low PNI was significantly associated with sex (P=0.0117), preoperative serum carcino embryonic antigen levels (P=0.0228), and postoperative recurrence (P<0.0001). In multivariate analysis, PNI (RR: 9.243; 95% CI: 3.662 25.823; P<0.0001), pleural invasion (RR: 8.664; 95% CI: 2.510-38.056; P=0.0005), and intratumoral blood vessel invasion (RR: 3.151; 95% CI: 1.259-7.681; P=0.0152) were independent prognostic factors. The low-PNI group had a significantly shorter recurrence-free survival than the high-PNI group, regardless of pathological T factors (T1a, P=0.0422; T1b, P<0.0001; T2a, P=0.0098). CONCLUSIONS: The preoperative PNI level is a simple and novel predictor of recurrence in stage I NSCLC patients, and might help identify patients who will need multimodality therapy such as induction or adjuvant therapy. PMID- 27393502 TI - Air bronchogram: A potential indicator of epidermal growth factor receptor mutation in pulmonary subsolid nodules. AB - OBJECTIVES: Evaluation of pulmonary subsolid nodule is a longstanding clinical problem. We aimed to validate the computed tomography (CT) features correlating with pathological invasiveness and to explore any imaging findings associated with epidermal growth factor receptor (EGFR) mutation in lung adenocarcinoma. METHODS: A total of 204 patients with pathologically proven stage IA adenocarcinoma who had preoperative CT and data on EGFR status were enrolled in this retrospective study. Quantitative CT features including tumor size and solid volume proportion (SVP) were measured on multiplanar reconstructed images. Pathological analysis was stratified into adenocarcinoma in situ and minimally invasive adenocarcinoma (AIS/MIA), and invasive adenocarcinomas (IAs). RESULTS: There were 93 AIS/MIA and 111 IAs. EGFR mutation was detected in 109 (53.4%) cases. In radiopathological analysis, IAs were significantly in larger tumor size (15.8mm vs. 10.9mm), higher SVP (18.3% vs. 1.1%) and more likely to present air bronchogram, vascular invasion, lobulated/irregular shape, non-smooth margin and pleural tag than AIS/MIA. The multivariate logistic regression indicated that tumor size (OR=1.337) and SVP (OR=1.198) were significant differentiating factors of IAs from AIS/MIA. In radiogenomic analysis, EGFR status differed in tumor size, air bronchogram and margin. The multivariate logistic regression disclosed that the presence of an air bronchogram (OR=3.451) was significantly associated with EGFR mutation after adjustment for age, gender and smoking status. CONCLUSIONS: In subsolid nodules, tumor size and SVP were significant predictors of pathological invasiveness. In addition, the presence of air bronchogram was suggestive of activated EGFR mutation. PMID- 27393503 TI - Temporal changes of EGFR mutations and T790M levels in tumour and plasma DNA following AZD9291 treatment. AB - AZD9291, a T790M specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has demonstrated impressive response rates in tumours harbouring the EGFR T790M resistance mutation. Emergence of resistance to AZD9291 has been shown to occur through several different mechanisms including the development of new mutations (e.g. C797S) in the EGFR tyrosine kinase domain. We studied two patients with paired tumour biopsies and blood samples pre- and post-progression on AZD9291 to explore possible resistance mechanisms. Pre- and Post-AZD9291 tumour biopsies as well as serial plasma samples were collected from two patients on the AURA clinical study (AZD9291 First Time in Patients Ascending Dose study). Droplet digital PCR (ddPCR) assays were used to quantify T790M, the driver EGFR mutation, and the C797S mutation in genomic DNA from paired tumour biopsies and plasma cell-free DNA. In the first patient, both EGFR T790M and L858R became undetectable in the plasma within 1 month after treatment with AZD9291. However, the T790M and the original L858R mutation re-emerged with radiologically confirmed resistance to AZD9291. In patient two, the levels of T790M were undetectable at the time of radiological resistance to AZD9291 but increasing levels of the original EGFR exon 19 deletion was detected. MET amplification was detected in a biopsy performed on progression. The EGFR C797S mutation was not detected in either patient at the time of relapse. ddPCR of cell free DNA enables real time monitoring of patients on 3rd generation TKIs. As resistance mechanisms are variable, monitoring levels of the initial activating EGFR mutation may facilitate more reliable detection of progression. PMID- 27393505 TI - Effects of para-toluenesulfonamide intratumoral injection on non-small cell lung carcinoma with severe central airway obstruction: A multi-center, non-randomized, single-arm, open-label trial. AB - BACKGROUND: Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). OBJECTIVES: To determine the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. METHODS: Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. RESULTS: In full-analysis set (N=88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%-69.5%), bronchoscopy: 48.9% (95%CI: 38.1%-59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%-54.2%), bronchoscopy: 29.6% (95%CI: 20.3%-40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16-0.53 liters), FEV1 (mean difference: 0.27 liters, 95%CI: 0.07-0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9-74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6.9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9-10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). CONCLUSION: PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO. PMID- 27393506 TI - Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1) and strong immune-cell infiltration by TCD3 cells and macrophages. AB - OBJECTIVES: Pulmonary sarcomatoid carcinomas (SC) are rare tumors, associated with worse prognosis and resistant to platinum-based regimens. Therapies targeting the PD-1/PD-L1 pathway are an emerging treatment for lung cancer. By characterizing intra-tumoral immune infiltration and evaluating PD-L1 expression, it could be possible to predict the efficacy of these new treatments. MATERIALS AND METHODS: From 1997 to 2013, data from all patients with SC who underwent lung resection was collected. Tumor-immune infiltration and PD-L1 expression were studied by immunochemistry tests, analyzing CD3 (clone SP7), CD4 (clone 1F6), CD8 (clone C8/144b), CD20 (clone L26), CD163 (clone 10D6), MPO (clone 59A5), and PD L1 (clone 5H1). Results were compared to those of 54 NSCLC. RESULTS: In total, 75 SC were included. Forty (53%) SC expressed PD-L1 vs 11 NSCLC (20%) (p<0.0001). CD3+ tumor-infiltrating lymphocytes and CD163+ tumor-associated macrophages were more important in SC than in NSCLC (median 23% [17-30] of tumoral surface vs 17% [7-27], p=0.011 and 23% [17-30] vs 20% [13-23], p=0.002, respectively). In SC, the presence of Kirsten Ras (KRAS) mutations, blood vessel invasion, and TTF1+ positivity were associated with PDL1 expression. On multivariate analysis, only CD163+ macrophages and blood-vessel invasion were associated with tumoral PD-L1 expression. High levels of tumor-infiltrating lymphocytes (CD3+ or CD4+ and not CD8+) constituted a factor of good prognosis on survival. Interestingly, PD-L1 expression distinguishes subpopulations within tumor-infiltrating lymphocytes (CD3+ or CD4+) with different prognosis CONCLUSIONS: PD-L1 expression was higher in SC than in NSCLC as well as immune-cell infiltration by TCD3 cells and macrophages. This suggests that targeting the PD-1/PD-L1 pathway could represent a new potential therapy. PMID- 27393504 TI - Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population. AB - OBJECTIVES: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. MATERIALS AND METHODS: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51*10(-5)) in an independent set of 866 cases and 796 controls in stage 2. RESULTS AND CONCLUSION: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3*10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8*10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3*10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans. PMID- 27393507 TI - High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post osimertinib progression. AB - Third-generation EGFR TKI has been approved in the US and EU for the treatment of EGFR mutant T790M+ NSCLC patients that are resistant to first- or second generation EGFR TKIs. Here we report a patient who developed resistance to osimertinib after a confirmed partial response for 9 months. Pre-osimertinib and post-osimertinib tumor biopsy revealed the emergence of high level of MET amplification (30 copies) post osimertinib treatment. Patient was treated with single agent crizotinib, a known MET inhibitor, with transient symptomatic benefit. MET amplification is one potential resistance mechanism to osimertinib and combination of osimertinib and a MET inhibitor should be investigated post osimertinib progression in EGFR mutant T790M+ NSCLC patients whose harbored acquired MET amplification. PMID- 27393508 TI - Spectral sensing for tissue diagnosis during lung biopsy procedures: The importance of an adequate internal reference and real-time feedback. AB - OBJECTIVES: Difficulties in obtaining a representative tissue sample are a major obstacle in timely selecting the optimal treatment for patients with lung cancer or other malignancies. Having a modality to provide needle guidance and confirm the biopsy site selection could be of great clinical benefit, especially when small masses are targeted. The objective of this study was to evaluate whether diffuse reflectance spectroscopy (DRS) at the tip of a core biopsy needle can be used for biopsy site confirmation in real time, thereby enabling optimized biopsy acquisition and improving diagnostic capability. MATERIALS AND METHODS: We included a total of 23 patients undergoing a routine computed tomography (CT) guided transthoracic needle biopsy of a lesion suspected for lung cancer or metastatic disease. DRS measurements were acquired during needle insertion and clinically relevant parameters were extracted from the spectral data along the needle paths. Histopathology results were compared with the DRS data at the final measurement position. RESULTS: Analysis of the collective data acquired from all enrolled subjects showed significant differences (p<0.01) for blood content, stO2, water content, and scattering amplitude. The identified spectral contrast matched the final pathology in 20 out of 22 clinical cases that could be used for analysis, which corresponds with an overall diagnostic performance of 91%. Three cases underlined the importance of adequate reference measurements and the need for real time diagnostic feedback. Continuous real time DRS measurements performed during a biopsy procedure in one patient provided clear information with respect to the variation in tissue and allowed identification of the tumour boundary. CONCLUSIONS: The presented technology creates a basis for the design and clinical implementation of integrated fibre-optic tools for a variety of minimal invasive applications. PMID- 27393509 TI - Clinical and pathologic features of lung cancer expressing programmed cell death ligand 1 (PD-L1). AB - BACKGROUND: Programmed cell death 1 (PD-1) negatively regulates antigen receptor signaling upon binding by either of its ligands, programmed cell death ligand 1 or 2 (PD-L1/2). Blockade of this interaction with either PD-1 or PD-L1 antibodies has been successful in the treatment of human cancer, especially melanoma and non small cell lung cancer. PD-L1 expression has been proposed as a predictor of tumor response. However, the relationships between PD-L1 expression and various clinicopathological characteristics remain unclear. MATERIALS AND METHODS: PD-L1 expression was examined in 220 non-small cell lung cancer specimens that were consecutively resected at our hospital after validating the E1L3N antibody immunohistochemical assay by comparing IHC and RT-PCR data for lung cancer cell lines. We evaluated the relationships between PD-L1 positivity, several clinical factors and the immunohistochemical expression of epithelial-mesenchymal transition (EMT), cancer stem cell and proliferative markers. RESULTS: PD-L1 was expressed in 22% of lung adenocarcinomas and 60% of squamous cell lung cancers. There was no significant association between PD-L1 expression and clinicopathological features in squamous cell lung cancer. However, in patients with lung adenocarcinoma, PD-L1 expression was significantly correlated with solid subtype histology, vimentin expression, increased Ki-67 labeling index and poor prognosis by multivariate analysis. CONCLUSION: PD-L1 expression was associated with high proliferative activity and the EMT phenotype in adenocarcinoma but not in squamous cell carcinoma of the lung. PD-L1 expression was a significant poor prognostic factor in patients with lung adenocarcinoma. PMID- 27393510 TI - Toxicity of definitive and post-operative radiation following ipilimumab in non small cell lung cancer. AB - To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity. PMID- 27393511 TI - Tumor perimeter and lobulation as predictors of pleural recurrence in patients with resected thymoma. AB - OBJECTIVES: Recurrence of resected thymoma frequently occurs during follow-up, with pleural recurrence as the most common type. The aim of our study was to identify risk factors for pleural recurrence after complete resection of thymoma by investigating clinical, radiological, surgical, and pathological findings. MATERIALS AND METHODS: Retrospective study was performed with 309 patients who had undergone complete resection of thymoma between January 2000 and December 2013. Among these cases, the patients were divided into the no pleural recurrence group (n=285) and the pleural recurrence group (n=24). Radiologic parameters such as maximum tumor diameter, tumor perimeter that contacted the lung (TPCL) and lobulated tumor contour were measured based on computed tomography. A multivariate analysis was performed to estimate risk factors for pleural recurrence including maximum tumor diameter, TPCL, lobulated tumor contour, World Health Organization (WHO) histologic classification, and Masaoka-Koga (M-K) stage. RESULTS: The median follow-up period was 62 months. The pleural recurrence rate was 7.8% (24/309). After univariate analysis, longer maximum tumor diameter (p<0.001), longer TPCL (p<0.001), lobulated tumor contour (p=0.001), WHO histologic type B2, B3 (p=0.002), and M-K stage III/IV (p<0.001) demonstrated significant differences with risk factors of pleural recurrence. Multivariate analysis revealed that TPCL (per 1cm increase: hazard ratio [HR]: 1.040, 95% confidence interval [CI]: 1.019-1.061, p<0.001), lobulated tumor contour (HR: 5.883, CI: 1.201-28.824, p=0.029), WHO histologic classification B2/B3 (HR: 5.331, CI: 1.453-19.558, p=0.012) and advanced M-K stage (HR: 3.900, CI: 1.579 9.632, p=0.003) were significantly associated with pleural recurrence. CONCLUSION: TPCL and lobulated tumor contour as well as WHO histologic classification and M-K stage were independent predictors of pleural recurrence after thymoma resection. Our study demonstrated that radiologic parameters could be useful predictor of pleural recurrence in patients with resected thymoma. PMID- 27393512 TI - Real-life effectiveness of erlotinib as second-line treatment of stage IIIB/IV squamous non-small cell lung cancer: Results of the PEPiTA observational study. AB - OBJECTIVES: Erlotinib, an inhibitor of tyrosine kinase activity of the epidermal growth factor receptor, is effective in non-small cell lung cancer (NSCLC). Data on erlotinib use in squamous NSCLC are limited. This observational study aimed at evaluating the efficacy and safety of second-line erlotinib in patients with stage IIIB/IV squamous NSCLC in a real-life setting. MATERIAL AND METHODS: Patients with predominantly squamous stage IIIB/IV NSCLC, who failed first-line platinum-based therapy, were recruited and followed-up for 12 months. Patients underwent visits each trimester. Data were derived from case report forms, and functional assessment of cancer therapy-lung (FACT-L) questionnaires. RESULTS: A total of 152 patients were enrolled; the majority were males (90%) and mean age was 67.7 years. All patients had squamous (97%) or predominantly squamous (3%) NSCLC, of stage IIIB (21%) or IV (79%). Median progression free survival (PFS) and overall survival were 3 and 5.8 months, respectively. Disease progression was observed in the majority of the patients, mostly due to progression of primary tumour and/or metastatic sites, and led to death in 91/107 of patients. Of the 107 deaths reported, none were due to erlotinib. FACT-L questionnaires were interpretable up to the first visit and were in line with PFS data, showing a relatively good quality of life up to Month 3 (mean total score=78.8). No new or unexpected safety issues were reported. CONCLUSIONS: The results of this real life cohort study like those of previous phase III/IV subgroups study analyses indicate that erlotinib is a valuable option for second-line treatment of stage IIIB/IV squamous NSCLC. PMID- 27393513 TI - Smoking cessation interventions within the context of Low-Dose Computed Tomography lung cancer screening: A systematic review. AB - The integration of smoking cessation interventions (SCIs) within the context of lung cancer screening programs is strongly recommended by screening guidelines, and is a requirement for Medicare coverage of screening in the US. In Europe, there are no lung cancer screening guidelines, however, research trials are ongoing, and prominent professional societies have begun to recommend lung cancer screening. Little is known about the types and efficacy of SCIs among patients receiving low-dose computed tomography (LDCT) screening. This review addresses this gap. Based on a systematic search, we identified six empirical studies published prior to July 1, 2015, that met inclusion criteria for our review: English language, SCI for LDCT patients, and reported smoking-related outcomes. Three randomized studies and three single-arm studies were identified. Two randomized controlled trials (RCTs) evaluated self-help SCIs, whereas one pilot RCT evaluated the timing (before or after the LDCT scan) of a combined (counseling and pharmacotherapy) SCI. Among the single-arm trials, two observational studies evaluated the efficacy of combined SCI, and one retrospectively assessed the efficacy of clinician-delivered smoking assessment, advice, and assistance. Given the limited research to date, and particularly the lack of studies reporting results from RCTs, assumptions that SCIs would be effective among this population should be made with caution. Findings from this review suggest that participation in a lung screening trial promotes smoking cessation and may represent a teachable moment to quit smoking. Findings also suggest that providers can take advantage of this potentially teachable moment, and that SCIs have been successfully implemented in screening settings. Continued systematic and methodologically sound research in this area will help improve the knowledge base and implementation of interventions for this population of smokers at risk for chronic disease. PMID- 27393514 TI - Advanced non-Small cell lung cancer patients at the extremes of age in the era of epidermal growth factor receptor tyrosine kinase inhibitors. AB - OBJECTIVES: The clinical characteristics and survival of very young (<=40 years) and very old (>80years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients' clinical characteristics and prognosis. MATERIALS AND METHODS: Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included. Patients were divided into the following groups according to age: young (<=40 years), lower medium (41-60 years), higher medium (61-80years), and very old (>80years). RESULTS: Of the 555 patients, 20 (3.6%) patients were aged <=40 years and 60 (10.8%) patients were aged >80years. Young NSCLC patients had a lower BMI (p=0.003), more brain (p=0.016) and bone metastases (p=0.002) Very young lung cancer patients still have poor prognosis even they were EGFR mutant. (EGFR mutant vs. wild type patients, OS: 12 vs. 7.3 months, p=0.215) Very old NSCLC patients had a lower BMI (p=0.003) and poor ECOG PS (p=0.028). Positive EGFR mutation test reverses poor prognosis of elderly NSCLC patients. (EGFR mutant vs. wild type patients, OS: 13.2 vs. 4.9 months, p=0.003) CONCLUSION: We observed EGFR mutations reverse the poor prognosis of old patients with NSCLC. However, young patients with lung cancer have a poor prognosis even if they harbor EGFR mutations. PMID- 27393515 TI - Prior cancer does not adversely affect survival in locally advanced lung cancer: A national SEER-medicare analysis. AB - INTRODUCTION: Management of locally advanced non-small cell lung cancer is among the most highly contested areas in thoracic oncology. In this population, a history of prior cancer frequently results in exclusion from clinical trials and may influence therapeutic decisions. We therefore determined prevalence and prognostic impact of prior cancer among these patients. MATERIALS AND METHODS: We identified patients>65years of age diagnosed 1992-2009 with locally advanced lung cancer in the Surveillance, Epidemiology, and End Results-Medicare linked dataset. We characterized prior cancer by prevalence, type, stage, and timing. We compared all-cause and lung cancer-specific survival between patients with and without prior cancer using propensity score-adjusted Cox regression. RESULTS: 51,542 locally advanced lung cancer patients were included; 15.8% had a history of prior cancer. Prostate (25%), gastrointestinal (17%), breast (16%), and other genitourinary (15%) were the most common types of prior cancer, and 76% percent of prior cancers were localized or in situ stage. Approximately half (54%) of prior cancers were diagnosed within 5 years of the index lung cancer date. Patients with prior cancer had similar (propensity-score adjusted hazard ratio [HR] 0.96; 95% CI, 0.94-0.99; P=0.005) and improved lung cancer-specific (HR 0.84; 95% CI, 0.81-0.86; P<0.001) survival compared to patients with no prior cancer. CONCLUSIONS: For patients with locally advanced lung cancer, prior cancer does not adversely impact clinical outcomes. Patients with locally advanced lung cancer and a history of prior cancer should not be excluded from clinical trials, and should be offered aggressive, potentially curative therapies if otherwise appropriate. PMID- 27393516 TI - Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases. AB - Central nervous system (CNS) metastases occur in 30% of patients with advanced non-small cell lung cancer (NSCLC). Localized treatments targeting CNS metastases result in delays in systemic therapy administration and are associated with neurocognitive impairment. Nivolumab is an immune check-point inhibitor that is approved as a second-line treatment of NSCLC. Data regarding the intracranial activity of nivolumab is lacking. We retrospectively reviewed the efficacy and safety of nivolumab in five patients with advanced NSCLC and new/progressing intracranial metastases. Intracranial response was assessed by magnetic resonance imaging (MRI) using mRECIST v. 1.1 criteria. All patients had parenchymal brain metastases; two patients had leptomeningeal carcinomatosis diagnosed according to radiological criteria. All patients were asymptomatic and did not require corticosteroids or immediate local therapy. We observed one complete and one partial response in the brain. Stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved in one additional patient. Two patients progressed in the CNS. Time-to-response comprised 5 weeks and 9 weeks; both responses are still ongoing at the time of the report (24+ and 28+ weeks since start of treatment). Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS metastases-related grade>=3 adverse events were observed. Nivolumab might have intracranial activity and favorable safety profile in patients with CNS metastases secondary to NSCLC. Nivolumab CNS activity warrants further evaluation. PMID- 27393517 TI - Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma. AB - We report a case of crizotinib effectiveness in a heavily pretreated patient with a metastatic NSCLC initially considered IHC-positive and FISH-negative for ALK rearrangement. After repeated analyses of tumor samples, borderline ALK FISH positivity (18.5% positive cells) was demonstrated. PMID- 27393518 TI - Downregulation of SATB2 is critical for induction of epithelial-to-mesenchymal transition and invasion of NSCLC cells. AB - OBJECTIVES: The epithelial-to-mesenchymal transition (EMT) is considered as a key step in invasion of cancer cells. There are several regulator proteins responsible for induction of EMT, but underlying mechanisms are still unclear. SATB2 is an epigenetic regulator involved in osteoblastic differentiation. The role of SATB2 in EMT and invasion of NSCLC cells is unknown. Therefore, we aimed to explain roles of SATB2 with underlying molecular mechanisms in EMT and invasion of NSCLC cells. MATERIALS AND METHODS: We used A549 and NCI-H1650 cells as a model to evaluate the effects of SATB2 in EMT and invasion of NSCLC cells. Cell culture, western blot analysis, siRNA-mediated gene knockdown, and invasion assay were performed in this study. RESULTS AND CONCLUSION: In this study, we investigated the regulatory role of SATB2 expression in TGF-beta-induced EMT and invasion of NSCLC cells, and found that SATB2 is downregulated in A549 cells and TGF-beta can induce EMT in these cells, however, TGF-beta can not induce EMT in SATB2 expressing cells such as H1650, PC3, II-18, Hcc78 and Hcc193. Our results demonstrated that SATB2 knockdown is sufficient to induce generation of fibroblast-like morphology, EMT and invasion of NSCLC cells by upregulating the expressions of Slug, Twist and Zeb1. Moreover, SATB2 knockdown promotes TGF-beta induced EMT and invasion in NSCLC cells. These results strongly suggest that SATB2 prevents induction of EMT by suppressing expression of EMT-inducing transcription factors in NSCLC cells. Furthermore, SATB2 could inhibit tumour initiation by suppressing stemness marker genes such as CD44, Nanog, Oct-4A and Sox-2. Consequently, our results clearly indicate that SATB2 plays pivotal role in EMT, invasion and stemness of NSCLC cells. PMID- 27393519 TI - P2X7R modulation of visually evoked synaptic responses in the retina. AB - P2X7Rs are distributed throughout all layers of the retina, and thus, their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal whole mount preparation, the present study aimed to characterise the effect of P2X7R activation on light evoked, excitatory RGC ON-field excitatory post-synaptic potentials (fEPSPs) and on outer retinal electroretinogram (ERG) responses under comparable conditions. The pharmacologically isolated NMDA receptor-mediated RGC ON-fEPSP was reduced in the presence of BzATP, an effect which was significantly attenuated by A438079 and other selective P2X7R antagonists A804598 or AF27139. In physiological Krebs medium, BzATP induced a significant potentiation of the ERG a-wave, with a concomitant reduction in the b-wave and the power of the oscillatory potentials. Conversely, in the pharmacologically modified Mg2+-free perfusate, BzATP reduced both the a-wave and b-wave. The effects of BzATP on the ERG components were suppressed by A438079. A role for P2X7R function in visual processing in both the inner and outer retina under physiological conditions remains controversial. The ON-fEPSP was significantly reduced in the presence of A804598 but not by A438079 or AF27139. Furthermore, A438079 did not have any effect on the ERG components in physiological Krebs but potentiated and reduced the a-wave and b-wave, respectively, when applied to the pharmacologically modified medium. Therefore, activation of P2X7Rs affects the function in the retinal ON pathway. The presence of a high concentration of extracellular ATP would most likely contribute to the modulation of visual transmission in the retina in the pathophysiological microenvironment. PMID- 27393521 TI - [Not Available]. AB - The use of placebos within controlled clinical trials for the last 50 years suggests that psycho-physiological effects can be objectified and measured. These are related to the therapeutic results covered by the term "placebo effect". Since Beecher's pioneer article in 1955, this effect is recognised and cited in medical articles as being on average 35% effective on the majority of symptoms. However, the meaning of these measurement is questionable. For example, it does not take into account the spontaneous evolution of symptoms and diseases. In fact, the placebo effect is not the effect measured in the group treated by the placebo. The clinical trial drug controlled against placebo does not make it possible to measure what is thus wrongly called "the placebo effect". Is it possible then to measure and to objectify what is called the placebo effect? And if that is possible, how? This article calls into question the extent of the placebo effect evaluated by means of controlled clinical trials, without denying its importance in medical practice. Firstly it raises the epistemological problem of the real possibility, via experimentation, of objectifying psychological therapeutic effects. And secondly, the question is also raised of the interest for medical care of objectifying those effects. PMID- 27393520 TI - Effects of hormones on skin wrinkles and rigidity vary by race/ethnicity: four year follow-up from the ancillary skin study of the Kronos Early Estrogen Prevention Study. AB - OBJECTIVE: To measure skin wrinkles and rigidity in menopausal women of varying race/ethnicity with or without hormone therapy (HT) for up to four years. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Academic medical centers. PATIENT(S): Women (42-58 years of age) within 36 months of last menstrual period and enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). INTERVENTION(S): Treatment with 0.45 mg oral conjugated equine estrogens (CEE), transdermal E2 (50 MUg/d) with micronized P (200 mg daily), or placebo for 4 years. MAIN OUTCOME MEASURE(S): Skin wrinkles were assessed at 11 locations on the face and neck, and skin rigidity was assessed at the forehead and cheek at baseline and yearly for 4 years. RESULT(S): Neither total wrinkle score nor total rigidity score was significantly different at baseline or over the 4-year follow up among patients randomized to CEE, E2, or placebo. Skin wrinkle and rigidity scores were primarily affected by race/ethnicity, with scores being significantly different between races for almost all of the wrinkle parameters and for all of the rigidity measures. There was no association between race and response to HT for total wrinkle or rigidity scores. Black women had the lowest wrinkle scores compared with white women across all 4 years. In general, skin rigidity decreased in all groups over time, but black women had significantly reduced total facial rigidity compared with white women after 4 years. CONCLUSION(S): Race is the strongest predictor of the advancement of skin aging in the 4 years following menopause. HT does not appear to affect skin wrinkles or rigidity at most facial locations. CLINICAL TRIAL REGISTRATION NUMBER: NCT00154180. PMID- 27393522 TI - [Not Available]. AB - The purpose of this paper is to examine the eventual benefits of treatment with calcium channel blockers in post-myocardial infarction, through an overview of main placebo-controlled trials that have been conducted to test this therapeutic in acute coronary syndromes. It appears obvious that the vast majority of these trials was conducted in the pre-reperfusion era and failed to demonstrate a reduction in mortality. To conclude, the superiority of a therapy with calcium antagonists over a placebo in the management of post-myocardial infarction remains unknown. In contrast, adverse effects associated with the prescription of calcium antagonists are well known. PMID- 27393523 TI - [Not Available]. AB - Specificity of antifungals use in paediatric patients is linked to mycoses epidemiology in this population. Pharmacokinetics vary with patient age. Although studies are in progress, pharmacokinetic data in children are limited in number for most antifungals. Among antifungal agents, those approved in France for use in children are rare. Adverse event frequency can differ in children, as compared to frequency in adults, and drug interaction should be a major worry. Relative interest and cost of available forms in the paediatric population in not always taken into account. For each different situation, an optimal strategy of antifungals use in children should be determined. PMID- 27393524 TI - [Not Available]. AB - The non-steroidal anti-inflammatory drugs (NSAID) especially the arylcarboxylic, are widely prescribed for their different properties. The renal adverse events are rare but often serious. We have reviewed the French experience for the following eight years period: January 1995 to December 2002. Three hundred and nine cases have been reported to the French Pharmacovigilance system during that period including 275 adults, 29 children and 5 new-born babies. In 247 cases (80%), the presentation was an acute renal failure occuning few days after treatment onset but not always of the prerenal type. Overall 34 patients needed one or more dialysis session; the majority recovered either completely or partially, but nevertheless, we had to deplore 5 deaths. These major renal complications were observed with all available NSAID on the French market, including ibuprofen which was often prescribe as pain-reliever. With this data together with international information, the French Drug Agency decided to modify the summary of products characteristics of these NSAID. PMID- 27393525 TI - [Not Available]. PMID- 27393526 TI - Taxonomic Knowledge of Children With and Without Cochlear Implants. AB - PURPOSE: The purpose of this study was to compare the taxonomic vocabulary knowledge and organization of children with cochlear implants to (a) children with normal hearing matched for age, and (b) children matched for vocabulary development. METHOD: Ten children with cochlear implants, 10 age-matched children with normal hearing, and 10 vocabulary-matched children with normal hearing participated in this study. The children completed 2 experimental tasks: a forced choice taxonomic sorting task, and a naming task requiring the children to use labels at multiple taxonomic levels. RESULTS: In the first task, the children in the cochlear implant group sorted pictures with accuracy consistent with the age matched group. In the second task, the children with cochlear implants demonstrated delayed knowledge of superordinate relations as compared with the age-matched group, similar to the vocabulary-matched group. However, the children with cochlear implants did not demonstrate delayed knowledge of basic or subordinate relations. CONCLUSION: The children with cochlear implants demonstrated a delay in use of superordinate taxonomic labels as compared with the children with normal hearing of the same age, which may lead to later difficulties with academic performance. PMID- 27393530 TI - Connectivity of diagnostic technologies: improving surveillance and accelerating tuberculosis elimination. AB - In regard to tuberculosis (TB) and other major global epidemics, the use of new diagnostic tests is increasing dramatically, including in resource-limited countries. Although there has never been as much digital information generated, this data source has not been exploited to its full potential. In this opinion paper, we discuss lessons learned from the global scale-up of these laboratory devices and the pathway to tapping the potential of laboratory-generated information in the field of TB by using connectivity. Responding to the demand for connectivity, innovative third-party players have proposed solutions that have been widely adopted by field users of the Xpert((r)) MTB/RIF assay. The experience associated with the utilisation of these systems, which facilitate the monitoring of wide laboratory networks, stressed the need for a more global and comprehensive approach to diagnostic connectivity. In addition to facilitating the reporting of test results, the mobility of digital information allows the sharing of information generated in programme settings. When they become easily accessible, these data can be used to improve patient care, disease surveillance and drug discovery. They should therefore be considered as a public health good. We list several examples of concrete initiatives that should allow data sources to be combined to improve the understanding of the epidemic, support the operational response and, finally, accelerate TB elimination. With the many opportunities that the pooling of data associated with the TB epidemic can provide, pooling of this information at an international level has become an absolute priority. PMID- 27393531 TI - Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings. AB - The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert((r)) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes. PMID- 27393532 TI - Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment. AB - In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients. PMID- 27393533 TI - Prevalence of pulmonary tuberculosis in adult population of Tanzania: a national survey, 2012. AB - SETTING: Tanzania is classified as one of the 22 high tuberculosis (TB) burden countries; however, the true burden of TB disease in the country remains unknown. OBJECTIVE: To assess the prevalence of bacteriologically confirmed pulmonary TB (PTB) in the adult population. DESIGN: This was a community-based cluster randomised survey with proportional-to-population-size selection of primary sampling units (districts). Participants were screened for TB using a symptom questionnaire and chest X-ray (CXR). Those with abnormal CXR and/or at least one symptom suggestive of TB were classified as individuals with presumptive TB, and asked to submit three sputum specimens for smear microscopy and culture. RESULTS: The weighted prevalence for sputum smear-positive TB cases was 249 per 100 000 adult population (95%CI 192-305) and that for bacteriologically confirmed TB cases was 293/100 000 (95%CI 228-358). Individuals aged ?45 years comprised 55% (71/129) of the identified smear-positive cases, but just 28% (6793/24 648) of the notified TB cases. CXR screening identified more TB cases than symptom screening. When weighted for human immunodeficiency virus prevalence among notified new smear-positive cases, the overall case detection of incident TB cases in 2012 was between 37% and 48%. CONCLUSIONS: The prevalence of sputum smear-positive PTB and bacteriologically confirmed PTB in the adult population was higher than previous World Health Organization estimates. There is a potential underestimation of the number of bacteriologically confirmed PTB cases in the adult population. The age distribution of prevalent cases suggests an epidemiological shift towards the older generations, which has been a sign of successful TB control activities in the past. However, the survey shows that many infectious TB cases are currently missed by the National Tuberculosis Programme. PMID- 27393535 TI - Longitudinal clustering of tuberculosis incidence and predictors for the time profiles: the impact of HIV. AB - BACKGROUND: Portugal remains the country with the highest tuberculosis (TB) incidence in Western Europe. OBJECTIVES: To identify longitudinal trends in TB incidence in Portugal from 2002 to 2012 and investigate the longitudinal effect of sociodemographic and health-related predictors among the resident population on the TB incidence rate. METHODS: We used data from the National Tuberculosis Surveillance System and other national institutions. K-means longitudinal clustering algorithm was performed on TB incidence time profiles from districts of Portugal. RESULTS: Three longitudinal profiles for the TB incidence rate of Portugal were identified. In all of them, TB incidence decreased over time. Among all studied sociodemographic and health-related predictors, human immunodeficiency virus (HIV) notification rate and unemployment were shown to have (positive) significant effects on TB incidence. In particular, the greatest effects were found for the HIV notification rate. CONCLUSIONS: Our study supports the view that combined TB-HIV strategies and the improvement of social determinants can contribute to decreases in TB incidence. PMID- 27393534 TI - Trend in the incidence of smear-positive tuberculosis in a district in South India after DOTS implementation. AB - SETTING: One baseline and three repeat surveys of the prevalence of tuberculosis (TB) disease were conducted in 1999-2008 in rural South India, where the DOTS strategy was implemented in 1999. The impact of DOTS on prevalence was documented, but not its impact on incidence. OBJECTIVE: To ascertain epidemiological trends in the incidence of smear-positive TB. DESIGN: All persons aged ?15 years (range 83 000-92 000) were examined using chest radiography (CXR); chest symptoms and history of anti-tuberculosis chemotherapy were noted in all four surveys. Sputum was collected from eligible participants and tested using direct smear and culture, and for drug susceptibility. As follow-up surveys were not frequent, survey cases and cases directly notified under DOTS were combined to estimate the incidence of smear-positive TB. RESULTS: Coverage was consistently high in all the repeat surveys, at ?80% for CXR and symptom recording, and at ?95% for sputum examination. The annual incidence of smear positive TB was respectively 112, 80 and 76 per 100 000 population in 2001-2003, 2004-2006 and 2006-2008. The overall decline observed was 7.5% per annum. CONCLUSION: A well-implemented DOTS strategy can lead to a reduction in the TB burden in the community. PMID- 27393536 TI - High prevalence of tuberculosis in newly enrolled HIV patients in Zambia: need for enhanced screening approach. AB - SETTING: Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed. OBJECTIVE: We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees. DESIGN: Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert((r)) MTB/RIF testing was performed retrospectively. RESULTS: From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/MUl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific. CONCLUSIONS: High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population. PMID- 27393537 TI - Incident tuberculosis in HIV-positive children, adolescents and adults on antiretroviral therapy in South Africa. AB - OBJECTIVE: To evaluate the association between age and incident tuberculosis (TB) among human immunodeficiency virus (HIV) infected patients receiving antiretroviral treatment (ART) in South Africa. DESIGN: Prospective cohort analysis among HIV-infected patients initiating ART between April 2004 and April 2012. Generalized estimating equations (GEE) were used with modified Poisson regression clustered by treatment site as a function of sex, age, nucleoside reverse transcriptase inhibitor, CD4 count, hemoglobin levels and year of ART initiation. Cumulative incidence functions stratified by age and controlling for death as a competing risk were used to graphically display incident TB. RESULTS: Although non-significant, GEE models showed that patients aged <1 year had a 40% increase in risk of TB compared to those aged 30-39.9 years. Results also showed that male patients, those with low CD4, those with low hemoglobin and those who initiated ART before 2010 were at increased risk of TB. CONCLUSIONS: Our results show that patients aged <1 year, males, patients with low CD4 and those with low hemoglobin at ART initiation are at increased risk of incident TB in the first 24 months of ART. Given the known transmission risk factors for children living in households with a TB contact, reducing TB incidence in HIV-positive adults could substantially impact the risk of TB in young children. PMID- 27393538 TI - Burden of disease and risk factors for death among children treated for tuberculosis in Malawi. AB - SETTING: Tuberculosis (TB) is a leading cause of childhood death. Patient-level data on pediatric TB in Malawi that can be used to guide programmatic interventions are limited. OBJECTIVE: To describe pediatric TB case burden, disease patterns, treatment outcomes, and risk factors for death and poor outcome. DESIGN: We conducted a retrospective cohort study utilizing routine data. Odds ratios (ORs) for factors associated with poor outcome and death were calculated using generalized estimating equations. RESULTS: Children represented 8% (371/4642) of TB diagnoses. The median age was 7 years (interquartile range 2.8-11); 32.8% (113/345) were human immunodeficiency virus (HIV) infected. Of these, 54.0% were on antiretroviral therapy (ART) at the time of anti tuberculosis treatment (ATT) initiation, 21.2% started ART during ATT, and 24.8% had no documented ART. The treatment success rate was 77.3% (11.2% cured, 66.1% completed treatment), with 22.7% experiencing poor outcomes (9.5% died, 13.2% were lost to follow-up). Being on ART at the time of ATT initiation was associated with increased odds of death compared to beginning ART during treatment (adjusted OR 2.75, 95%CI 1.27-5.96). CONCLUSION: Children represent a small proportion of diagnosed TB cases and experience poor outcomes. Higher odds of death among children already on ART raises concerns over the management of these children. Further discussion of and research into pediatric-specific strategies is required to improve case finding and outcomes. PMID- 27393539 TI - Implementation of isoniazid preventive therapy in children aged under 5 years exposed to tuberculosis in Benin. AB - SETTINGS: Two large tuberculosis (TB) centres under a well-functioning National TB Programme (NTP) in Benin, West Africa. OBJECTIVE: To assess the feasibility and results of integrating a programme of isoniazid preventive therapy (IPT) in children aged <5 years exposed to TB as part of the existing routine activities of the NTP. METHOD: All children aged <5 years living in the household of a patient with smear-positive pulmonary TB were examined by a doctor and received IPT if no evidence of TB was detected. The children were followed clinically by a nurse for 6 months. RESULTS: From January 2013 to June 2014, 496 children were examined and prescribed IPT among 499 notified contacts; 86% adhered to IPT for at least 6 months. There were six deaths and three cases of active TB among the children, all during the first 3 months of follow-up. CONCLUSIONS: In an African country with moderate TB incidence and a well-functioning NTP, the integration of IPT into the NTP for children aged <5 years exposed to TB in the family was feasible based on simple tools associated with the follow-up of index cases. The rate of adherence to IPT was high. PMID- 27393540 TI - Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study. AB - BACKGROUND: Identifying source cases of children exposed to tuberculosis (TB) is challenging. We examined the time-point of obtaining contact information of TB source cases in human immunodeficiency virus (HIV) infected and HIV-exposed uninfected (HEU) children in a randomised, placebo-controlled trial of pre exposure to isoniazid prophylaxis. METHODS: A total of 543 HIV-infected and 808 HEU infants without TB exposure aged 3-4 months were enrolled between 2004 and 2008. At 3-monthly follow-up, infants were evaluated for TB and care givers were asked about new TB exposure. RESULTS: In total, 128 cases of TB disease and 40 deaths were recorded among 19% (105/543) of the HIV-infected and 8% (63/808) of the HEU children; 229 TB contact occasions were reported in 205/1351 (15%) children, of which 83% (189/229) were in the household. Of the 189 household contacts, 108 (53%) underwent microbiological evaluations; 81% (87/108) were positive. HIV-infected and HEU infants had similar frequencies of TB contact: in 48% of infants with definite TB, 58% with probable TB and 43% with possible TB. Of 128 children diagnosed with TB, a TB contact was identified for 59. Of these, 29/59 (49%) were identified at or after the child's TB diagnosis. CONCLUSION: TB source cases are often identified at or after a child's TB diagnosis. More effort is required for earlier detection. PMID- 27393541 TI - Rifampicin resistance after treatment for latent tuberculous infection: a systematic review and meta-analysis. AB - SETTING: Treatment for latent tuberculous infection (LTBI) reduces the risk of tuberculosis (TB) disease. Shorter, rifamycin-containing regimens have been shown to be as effective as 6 months of isoniazid and superior with regard to safety and completion rate. It is unknown whether preventive therapy with rifamycins increases resistance to the drugs used. OBJECTIVE: To determine whether treatment for LTBI with rifamycin-containing regimens leads to significant development of resistance against rifamycins. DESIGN: Systematic review and meta-analysis. RESULTS: We included six randomised-controlled trials of rifamycin-containing regimens for LTBI treatment that reported drug resistance. There was no statistically significant increased risk of rifamycin resistance after LTBI treatment with rifamycin-containing regimens compared to non-rifamycin-containing regimens (RR 3.45, 95%CI 0.72-16.56; P = 0.12) or placebo (RR 0.20, 95%CI 0.02 1.66; P = 0.13). CONCLUSION: Preventive treatment with rifamycin-containing regimens does not significantly increase rifamycin resistance. Programmatic management of LTBI requires the creation of sound surveillance systems to monitor drug resistance. PMID- 27393542 TI - Prevalence and incidence rates of latent tuberculous infection in a large prison in Iran. AB - BACKGROUND: Prisons can act as reservoirs of tuberculous infection. Previous studies have shown that the prevalence of latent tuberculous infection (LTBI) is high in prisons. OBJECTIVE: To investigate the prevalence and incidence rates of LTBI and contributing factors in a prison population in Iran. METHODS: In March 2013, inmates at the Hamadan Central Prison were invited to participate in a voluntary two-stage screening programme using the tuberculin skin test (TST). In the first stage, the standard TST was administered and read, and was repeated in negative cases to identify cases with delayed TST reactivity and boosted reaction. In the second stage, inmates with a true-negative TST underwent repeat screening 6 months later to identify incident LTBI. Information about risk factors was obtained using structured interviews. RESULTS: Among 1208 screened inmates, TST positivity was recorded in 756 cases (prevalence 62.6%). HIV positive inmates and cigarette smokers were also more likely to have LTBI. In 380 inmates returning for a follow-up visit, the 6-month incidence rate was 7.6%. Two cases of pulmonary tuberculosis were identified during the period of study. CONCLUSIONS: LTBI prevalence and incidence rates among Iranian prisoners are high. Comprehensive plans are needed to for effective TB control among prisoners. PMID- 27393543 TI - A mixed-methods evaluation of adherence to preventive treatment among child tuberculosis contacts in Indonesia. AB - BACKGROUND: Tuberculosis (TB) can be prevented using isoniazid preventive therapy (IPT) among child contacts. However, the benefits of IPT depend on adherence to at least 6 months of daily treatment. A greater understanding of the barriers to and facilitators of adherence to IPT in resource-poor settings is required to optimise the benefits. METHODS: We prospectively evaluated adherence to IPT and its associated factors among child contacts (age 0-5 years) eligible for IPT. We undertook in-depth interviews with care givers and a focus group discussion with health care workers, which were thematically analysed to explore barriers to and facilitators of adherence from the perspective of both care givers and health workers. RESULTS: Of 99 eligible children, 49 (49.5%) did not complete 6 months of IPT. Children whose care giver collected their IPT medications from primary health centres were more likely to have incomplete adherence than those who collected them from hospitals (aOR 2.9, 95%CI 1.1-7.8). Thematic analyses revealed major barriers to and facilitators of adherence: regimen-related, care giver-related and health care-related factors, social support and access. Many of these factors are readily modifiable. CONCLUSION: Providing information about IPT and improving accessibility for care givers to receive IPT at the primary health care facility should be priorities to facilitate implementation. PMID- 27393545 TI - Adaptive trials for tuberculosis: early reflections on theory and practice. AB - SETTING: Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. OBJECTIVE: To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. DESIGN: In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. RESULTS: Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. CONCLUSION: Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice. PMID- 27393544 TI - 'They prefer hidden treatment': anti-tuberculosis drug-taking practices and drug regulation in Karakalpakstan. AB - SETTING: The joint Medecins Sans Frontieres/Ministry of Health Multidrug Resistant Tuberculosis (MDR-TB) Programme, Karakalpakstan, Uzbekistan. OBJECTIVE: Uzbekistan has high rates of MDR-TB. We aimed to understand patients' and prescribers' attitudes to anti-tuberculosis drug prescription, regulation and drug-taking behaviour. METHODS: Participants (12 patients, 12 practitioners) were recruited purposively. Data were gathered qualitatively using field notes and in depth interviews and analysed thematically. FINDINGS: Our analysis highlighted two main themes. First, shame and stigma were reported to increase the likelihood of self-treatment and incorrect use of anti-tuberculosis drugs, most commonly at the initial stages of illness. A health system failure to promote health information was perceived, leading to wrong diagnoses and inappropriate therapies. Motivated by shame, patients hid their condition by resorting to drug treatment options outside the programme, compounding the risk of chaotic management and dissemination of erroneous information through lay networks. Second, positive influences on treatment were reported through patients, practitioners and peers working effectively together to deliver the correct information and support, which acted to normalise TB, reduce stigma and prevent misuse of anti-tuberculosis drugs. CONCLUSION: Effective case finding, patient support and community education strategies are essential. Patients, practitioners and peers working together can help reduce stigma and prevent misuse of anti tuberculosis drugs. PMID- 27393546 TI - Detection of katG and inhA mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis. AB - BACKGROUND: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE: To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique. DESIGN: Descriptive study of 311 isolates from Ribeirao Preto, Sao Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType((r)) MTBDRplus. RESULTS: katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223). CONCLUSION: INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH. PMID- 27393547 TI - Comparison of TaqMan((r)) Array Card and MYCOTB(TM) with conventional phenotypic susceptibility testing in MDR-TB. AB - BACKGROUND: Although phenotypic drug susceptibility testing (DST) is endorsed as the standard for second-line drug testing of Mycobacterium tuberculosis, it is slow and laborious. METHODS: We evaluated the accuracy of two faster, easier methodologies that provide results for multiple drugs: a genotypic TaqMan((r)) Array Card (TAC) and the Sensititre((r)) MYCOTB(TM) plate. Both methods were tested at three central laboratories in Bangladesh, Tanzania, and Thailand with 212 multidrug-resistant tuberculosis (MDR-TB) isolates and compared with the laboratories' phenotypic method in use. RESULTS: The overall accuracy for ethambutol, streptomycin, amikacin, kanamycin, ofloxacin, and moxifloxacin vs. the phenotypic standard was 87% for TAC (range 70-99) and 88% for the MYCOTB plate (range 76-98). To adjudicate discordances, we re-defined the standard as the consensus of the three methods, against which the TAC and MYCOTB plate yielded 94-95% accuracy, while the phenotypic result yielded 93%. Some isolates with genotypic mutations and high minimum inhibitory concentration (MIC) were phenotypically susceptible, and some isolates without mutations and low MIC were phenotypically resistant, questioning the phenotypic standard. CONCLUSIONS: In our view, the TAC, the MYCOTB plate, and the conventional phenotypic method have similar performance for second-line drugs; however, the former methods offer speed, throughput, and quantitative DST information. PMID- 27393548 TI - Xpert((r)) MTB/RIF for detection of Mycobacterium tuberculosis from frozen string and induced sputum sediments. AB - SETTING: Although it is now widely used for tuberculosis (TB) diagnosis, Xpert((r)) MTB/RIF availability remains inadequate in low-resource settings. Moreover, its accuracy in testing stored samples from non-expectorating patients has not been evaluated. OBJECTIVE: To assess the performance of Xpert in frozen samples of induced sputum (IS) and sputum from string test (ST) from non expectorating individuals with presumed TB. DESIGN: This was a laboratory-based study of 377 ST and IS samples collected between March 2010 and March 2013 at a referral hospital in Uganda. Samples were decontaminated, centrifuged and cultured, and the resultant samples were frozen at -20 degrees C before Xpert evaluation. RESULTS: TB was detected in ST and IS samples from 19/163 (11.7%) children and 63/201 (29.4%) adults using culture. Xpert sensitivity in frozen sediments from children was 37.5% (95%CI 8.5-75.5) in ST and 41.7% (95%CI 15.2 72.3) in IS samples, with specificities of respectively 100% (95%CI 94.9-100) and 98.6% (95%CI 92.7-100). In adults, sensitivity was respectively 50% (95%CI 31.3 68.7) and 48.5% (95%CI 30.8-66.4) in ST and IS samples, with specificities of respectively 100% (95%CI 95.5-100) and 98.6% (95%CI 92.4-100). CONCLUSION: Given these results, and particularly the high specificity, the use of Xpert on frozen ST and IS sediment samples from both children and adults is promising. PMID- 27393549 TI - Xpert((r)) MTB/RIF detection of Mycobacterium tuberculosis from sputum collected in molecular transport medium. AB - BACKGROUND: The Xpert((r)) MTB/RIF assay is widely used for Mycobacterium tuberculosis detection. However, specimen transport remains a challenge. PrimeStore Molecular Transport Medium((r)) (PS-MTM) inactivates specimens and stabilizes DNA/RNA at ambient temperature for subsequent molecular detection. OBJECTIVE: To compare the detection of M. tuberculosis concentrations in PS-MTM using Xpert and real-time polymerase chain reaction (RT-PCR), and smear-positive sputum specimens collected using a flocked swab. METHODS: Dilutions of M. tuberculosis in PS-MTM and phosphate buffered saline (PBS) were analyzed using the Xpert assay and commercial RT-PCR. Smear-positive (1+ to 3+) sputum specimens (n = 17) were transferred by flocked swab into PS-MTM and PBS, and were compared to standard 1.0 ml sputum Xpert analysis. RESULTS: Using the Xpert assay, cycle threshold values from high M. tuberculosis concentrations in PS-MTM (>10(3) colony forming units [cfu]/ml) were increased compared to control. In contrast, M. tuberculosis samples containing <10(3) cfu/ml, i.e., low concentrations, suspended in PS-MTM resulted in detection down to 10 cfu/ml. Xpert detection efficiency in PS-MTM treated samples (63.2%) was improved compared to PBS controls (34.9%). Xpert detected M. tuberculosis in all sputum specimens collected by flocked swabs in PS-MTM, and correlated with routine Xpert detection. CONCLUSIONS: PS-MTM enhances M. tuberculosis detection at low concentrations of M. tuberculosis, and provides a simplified and efficient collection method for Xpert detection. PMID- 27393550 TI - Solitary pulmonary nodules due to non-tuberculous mycobacteriosis among 28 resected cases. AB - BACKGROUND: In some patients, non-tuberculous mycobacteria (NTM) infections manifest in solitary nodules (solitary nodular [SN] type) generally caused by Mycobacterium avium complex (MAC). In patients treated using surgical resection, the American Thoracic Society guidelines state that postoperative chemotherapy is not necessary in the absence of lesions, although there have been a few reports of such cases. METHODS: Twenty-eight patients diagnosed with NTM who underwent solitary pulmonary nodule resection at Toneyama Hospital, Osaka, Japan, between January 2000 and October 2012 were enrolled. We evaluated the influence of the surgical procedure and chemotherapy on outcomes in this retrospective study. RESULTS: Of the 28 patients, 12 were males and 16 were females; the mean age was 58.6 +/- 13.2 years. Twenty-five patients were asymptomatic and bronchoscopy was performed in 18; only 2 had a definitive diagnosis of NTM. The pathogen responsible was MAC in 27 patients and M. kansasii in 1. The surgical procedure used was wedge resection in 22 patients, segmentectomy in 1 and lobectomy in 5. Postoperative chemotherapy was administered to 9 patients. Twenty-six patients had no recurrence. CONCLUSION: We believe that wedge resection is a valid surgical intervention for SN type NTM; additional postoperative chemotherapy is unnecessary in cases with no residual lesions in the operated lung lobe. PMID- 27393552 TI - Could BAL Xpert((r)) MTB/RIF replace transbronchial lung biopsy everywhere for suspected pulmonary TB patients? PMID- 27393551 TI - Implementation and 8-year follow-up of an uninterrupted oxygen supply system in a hospital in The Gambia. AB - SETTING: A 42-bed hospital operated by the Medical Research Council (MRC) Unit in The Gambia. OBJECTIVE: To devise, test and evaluate a cost-efficient uninterrupted oxygen system in the MRC Hospital. DESIGN: Oxygen cylinders were replaced with oxygen concentrators as the primary source of oxygen. An uninterruptable power supply (UPS) ensured continuity of power. Hospital staff were trained on the use of the new system. Eight years post-installation, an analysis of concentrator maintenance needs and costs was conducted and user feedback obtained to assess the success of the system. RESULTS: The new system saved at least 51% of oxygen supply costs compared to cylinders, with savings likely to have been far greater due to cylinder leakages. Users indicated that the system is easier to use and more reliable, although technical support and staff training are still needed. CONCLUSION: Oxygen concentrators offer long-term cost savings and an improved user experience compared to cylinders; however, some technical support and maintenance are needed to upkeep the system. A UPS dedicated to oxygen concentrators is an appropriate solution for settings where power interruptions are frequent but short in duration. This approach can be a model for health systems in settings with similar infrastructure. PMID- 27393553 TI - Pellagra: a rare complication of isoniazid therapy. PMID- 27393554 TI - Heritability of in vitro phenotypes exhibited by murine adipose-derived stromal cells. AB - Adipose-derived stromal cells (ADSCs) exhibit significant potential as therapeutic agents to promote tissue regeneration. Success of ADSC-based therapies is dependent upon efficient cell expansion in vitro as well as postinjection survival in the caustic milieu of damaged tissue. Genetic background regulates ADSC proliferative capacity and stress resistance, but the extent of the genetic effect size is not completely defined. The present study aimed to quantify phenotypic ranges and heritability of in vitro ADSC characteristics. ADSCs were isolated from mice representing 16 genetically diverse inbred mouse strains, including 12 classical inbred strains and four wild derived strains. Cells were grown in vitro, and proliferative capacity and oxidative stress resistance were assessed. The fold change for ADSC growth ranged from 0.87 (BALB/cByJ) to 23.60 (POHN/DehJ), relative to original seeding density. The heritability of proliferative capacity was estimated to be 0.6462 (p = 9.967 * 10(-15)), and this phenotype was not associated with other ADSC traits. Cell viability following H2O2 treatment ranged from 39.81 % (CAST/EiJ) to 91.60 % (DBA/2 J), and the heritability of this phenotype was calculated as 0.6146 (p = 1.22 * 10(-12)). Relationships between cell viability and weight of the donor fat pad were also discovered. Donor genetic background is a major determinant of in vitro ADSC phenotypes. This study supports the development of forward genetics strategies to identify genes that underlie ADSC phenotypic diversity, which will inform efforts to improve cell-based therapies. PMID- 27393555 TI - [Intraoperative stress in orthopaedic spine surgery : Attending surgeon versus resident]. AB - INTRODUCTION: Requirements for orthopaedic spine surgeons include occupational skills, concentration, physical fitness and psychological stress resistance, depending on the attending surgeon's or the resident's position. MATERIAL AND METHODS: This study measured and evaluated stress-relevant cardiovascular parameters during 101 spinal surgical procedures of a 40-year old fellowship trained spine surgeon with 12 years of practice. A training computer, personal scales and a thermometer were used to record the duration of surgery, heart rate, weight loss and calorie burning. RESULTS: The average maximum heart rate as an attending surgeon (124 bpm) was significantly higher than the resident's heart rate (99 bmp). A higher stress level resulted in an increasingly higher average maximum heart rate according to the duration of surgery. The mean loss of body fluids at an average room temperature of 20.4 C after surgery was 0.82 kg (0 to 2.3 kg). The mean loss of body weight was calculated as 1.12% of the attending surgeon versus 0.59% of the resident. DISCUSSION: Increasing complexity, longer duration and a higher potential of intraoperative complications arouse a strong response from the attending surgeon. The observed cardiovascular parameters are similar to those of a moderate to intense workout such as cycling. Long lasting surgeries result in a weight loss equivalent to a mild dehydration ranging from 2 to 5% of body fluids. Increasing dehydration will eventually worsen cognitive, visual and motor skills. Results of this study suggest early rehydration and utilization of mental relaxation techniques to minimize risks during prolonged, complex spine surgeries. PMID- 27393556 TI - Shinella curvata sp. nov., isolated from hydrocarbon-contaminated desert sands. AB - The taxonomic position of a novel bacterial strain, designated C3T, isolated from hydrocarbon-contaminated desert sands was determined. Strain C3T was a Gram-stain negative, rod- to curved-rod-shaped and non-motile bacterium. It was able to grow at 4-45 degrees C (optima, 28- 35 degrees C) and at pH 6.1-8.8 (optima, 6.9 7.7). No added NaCl was required for growth of strain C3T and it tolerated up to 3.5 % (w/v) NaCl with optimal growth with 0.5-1.5 %. Catalase and oxidase were positive. C18 : 1omega6c/C18 : 1omega7c, C16 : 0, C12 : 0 aldehyde, C14 : 0 3 OH/iso-C16 : 0 I and C18 : 1omega7c 11-methyl were predominant fatty acids. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine were major polar lipids. The genomic DNA G+C content was 65.4 mol%. 16S rRNA gene sequence comparisons indicated that strain C3T represents a member of the genus Shinella within the family Rhizobiaceae of the class Alphaproteobacteria. Strain C3Tshowed a 16S rRNA gene sequence similarity of 98.39 % with Shinella kummerowiae CCBAU 25048T, 98.37 % with Shinella granuli Ch06T, 98.17 % with Shinella zoogloeoides I-16-MT, 97.74 % with Shinella fusca DC 196T, 97.46 % with Shinella yambaruensis MS4T and <96.68 % with other members of the family Rhizobiaceae. DNA-DNA hybridization values between strain C3T and the type strains of the nearest species were clearly below the 70 % threshold for species delineation. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of strain C3T as a representative of a novel species in the genus Shinella, for which the name Shinella curvata sp. nov. is proposed. The type strain is C3T (=KEMB 2255 446T=JCM 31239T). PMID- 27393557 TI - Does operative fixation affect outcomes of displaced medial epicondyle fractures? AB - PURPOSE: Long-term functional results remain equivocal between operative fixation and closed management of displaced humeral medial epicondyle fractures. The purpose of this study was to determine whether a functional difference exists between treatment types. METHODS: One hundred and forty patients with a displaced medial epicondyle fracture between 2007 and 2014 met the inclusion criteria. Of this large cohort, only 12 patients agreed to return to clinic at a mean follow up of 3 years for prospective evaluation. Data collection included radiographs, physical examination, validated outcome tools, and grip strength testing with a Jamar dynamometer. RESULTS: Both groups were comparable with regard to age, dominant side injured, length of follow-up, preinjury sports involvement, and initial displacement (10 mm operative vs. 9 mm nonoperative); however, half of the surgical group presented with an associated unreduced elbow dislocation versus 0 % in the nonoperative group. Both treatment methods resulted in high patient satisfaction and elbow function scores. There were four osseous nonunions (67 %) and one malunion (17 %) in the nonoperative group versus none in the operative group (p = 0.015). Patients treated nonoperatively had a nonsignificant decrease in grip strength (9 +/- 6 lbs) as compared to operative patients (6 +/- 5 lbs, medium effect size eta = 0.25, p = 0.25). CONCLUSIONS: In this small cohort, operative management of displaced medial epicondyle fractures resulted in a higher rate of fracture union and return to sports. Other objective and subjective measures were similar between the two treatment groups. PMID- 27393558 TI - Work and Health Questionnaire (WHQ): A Screening Tool for Identifying Injured Workers at Risk for a Complicated Rehabilitation. AB - Purpose Unintentional injuries occur frequently and many of the accident survivors suffer from temporary or permanent disabilities. Although most accident victims recover quickly, a significant fraction of them shows a complicated recovery process and accounts for the majority of disability costs. Thus, early identification of vulnerable persons may be beneficial for compensation schemes, government bodies, as well as for the worker themselves. Here we present the Work and Health Questionnaire (WHQ), a screening tool that is already implemented in the case management process of the Swiss Accident Insurance Fund (Suva). Moreover, we demonstrate its prognostic value for identifying workers at risk of a complicated recovery process. Methods A total of 1963 injured workers answered the WHQ within the first 3 months after their accident. All of them had minor to moderate accidental injuries; severely injured workers were excluded from the analyses. The anonymized individual-level data were extracted from insurance databases. We examined construct validity by factorial analyses, and prognostic validity by hierarchical multiple regression analyses on days of work disability. Further, we evaluated well-being and job satisfaction 18 months post-injury in a subsample of 192 injured workers (9.8 %) Results Factor analyses supported five underlying factors (Job Design, Work Support, Job Strain, Somatic Condition/Pain, and Anxiety/Worries). These subscales were moderately correlated, thus indicating that different subscales measured different aspects of work and health-related risk factors of injured workers. Item analysis and reliability analysis showed accurate psychometric properties. Each subscale was predictive at least for one of the evaluated outcomes 18 months post-injury. Conclusion The WHQ shows good psychometric qualities with high clinical utility to identify injured persons with multiple psychosocial risk factors. Thus, the questionnaire appears to be suitable for exploring different rehabilitation needs among minor to moderate injured workers. PMID- 27393559 TI - Dietary silver nanoparticles can disturb the gut microbiota in mice. AB - BACKGROUND: Humans are increasingly exposed via the diet to Ag nanoparticles (NP) used in the food industry. Because of their anti-bacterial activity, ingested Ag NP might disturb the gut microbiota that is essential for local and systemic homeostasis. We explored here the possible impact of dietary Ag NP on the gut microbiota in mice at doses relevant for currently estimated human intake. METHODS: Mice were orally exposed to food (pellets) supplemented with increasing doses of Ag NP (0, 46, 460 or 4600 ppb) during 28 d. Body weight, systemic inflammation and gut integrity were investigated to determine overall toxicity, and feces DNA collected from the gut were analyzed by Next Generation Sequencing (NGS) to assess the effect of Ag NP on the bacterial population. Ag NP were characterized alone and in the supplemented pellets by scanning transmission electron microscopy (STEM) and energy dispersive X-ray analysis (EDX). RESULTS: No overall toxicity was recorded in mice exposed to Ag NP. Ag NP disturbed bacterial evenness (alpha-diversity) and populations (beta-diversity) in a dose dependent manner. Ag NP increased the ratio between Firmicutes (F) and Bacteroidetes (B) phyla. At the family level, Lachnospiraceae and the S24-7 family mainly accounted for the increase in Firmicutes and decrease in Bacteroidetes, respectively. Similar effects were not observed in mice identically exposed to the same batch of Ag NP-supplemented pellets aged during 4 or 8 months and the F/B ratio was less or not modified. Analysis of Ag NP supplemented pellets showed that freshly prepared pellets released Ag ions faster than aged pellets. STEM-EDX analysis also showed that Ag sulfidation occurred in aged Ag NP-supplemented pellets. CONCLUSIONS: Our data indicate that oral exposure to human relevant doses of Ag NP can induce microbial alterations in the gut. The bacterial disturbances recorded after Ag NP are similar to those reported in metabolic and inflammatory diseases, such as obesity. It also highlights that Ag NP aging in food, and more specifically sulfidation, can reduce the effects of Ag NP on the microbiota by limiting the release of toxic Ag ions. PMID- 27393560 TI - Microbubble assisted polyhydroxybutyrate production in Escherichia coli. AB - BACKGROUND: One of the potential limitations of large scale aerobic Escherichia coli fermentation is the need for increased dissolved oxygen for culture growth and bioproduct generation. As culture density increases the poor solubility of oxygen in water becomes one of the limiting factors for cell growth and product formation. A potential solution is to use a microbubble dispersion (MBD) generating device to reduce the diameter and increase the surface area of sparged bubbles in the fermentor. In this study, a recombinant E. coli strain was used to produce polyhydroxybutyrate (PHB) under conventional and MBD aerobic fermentation conditions. RESULTS: In conventional fermentation operating at 350 rpm and 0.8 vvm air flow rate, an OD600 of 6.21 and PHB yield of 23 % (dry cell basis) was achieved. MBD fermentation with similar bioreactor operating parameters produced an OD600 of 8.17 and PHB yield of 43 % PHB, which was nearly double that of the conventional fermentation. CONCLUSIONS: This study demonstrated that using a MBD generator can increase oxygen mass transfer into the aqueous phase, increasing E. coli growth and bioproduct generation. PMID- 27393561 TI - A novel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies. AB - The aim of the present study was to develop a novel solubilization technique consisting of a nano-cocrystal suspension by integrating cocrystal and nanocrystal formulation technologies to maximize solubilization over current solubilizing technologies. Monodisperse carbamazepine-saccharin, indomethacin saccharin, and furosemide-caffeine nano-cocrystal suspensions, as well as a furosemide-cytosine nano-salt suspension, were successfully prepared with particle sizes of less than 300nm by wet milling with the stabilizers hydroxypropyl methylcellulose and sodium dodecyl sulfate. Interestingly, the properties of resultant nano-cocrystal suspensions were dramatically changed depending on the physicochemical and structural properties of the cocrystals. In the formulation optimization, the concentration and ratio of the stabilizers also influenced the zeta potentials and particles sizes of the resultant nano cocrystal suspensions. Raman spectroscopic analysis revealed that the crystalline structures of the cocrystals were maintained in the nanosuspensions, and were physically stable for at least one month. Furthermore, their dissolution profiles were significantly improved over current solubilization-enabling technologies, nanocrystals, and cocrystals. In the present study, we demonstrated that nano cocrystal formulations can be a new promising option for solubilization techniques to improve the absorption of poorly soluble drugs, and can expand the development potential of poorly soluble candidates in the pharmaceutical industry. PMID- 27393562 TI - Aptamer-mediated delivery of docetaxel to prostate cancer through polymeric nanoparticles for enhancement of antitumor efficacy. AB - Treatment of aggressive prostate cancer remains a great challenge due to inadequate drug distribution into the cancerous lesions after administration. This study aimed to develop aptamer-anchored nanoparticles (apt-NPs) for systemic delivery of docetaxel (DTX) and to evaluate the tumoricidal activity against the prostate cancer in vitro and in vivo. DTX-loaded apt-NPs (DTX-apt-NPs) were prepared by a solvent diffusion technique using functional PLGA-b-PEG and sodium oleate. DTX-apt-NPs were characterized by in vitro release, antitumor activity, cellular uptake and cytotoxic mechanisms. Pharmacokinetics and tissue distribution studies were performed in rats to investigate the biofate of DTX-apt NPs. Finally, the in vivo antitumor efficacy was examined on the LNCaP cells xenograft tumor model. The resulting DTX-apt-NPs were 93.6nm in particle size with narrow distribution and possessed a high entrapment efficiency (97.62%) and acceptable drug loading (8.91%). DTX-apt-NPs demonstrated an enhanced in vitro antitumor effect and marked cellular uptake compared with the solution formulation or conventional nanoparticles. The intracellular trafficking of DTX apt-NPs was shown to be an active transport process involving the clathrin dependent endocytosis. Anti-PSMA aptamer-mediated delivery was assumed mainly responsible for the enhanced antitumor efficacy. DTX-apt-NPs that can target to PSMA-overexpressed prostate cancer provide a feasible approach for systemic delivery of DTX to the cancerous prostate to achieve a fine prognosis. PMID- 27393563 TI - Alginate-based hybrid aerogel microparticles for mucosal drug delivery. AB - The application of biopolymer aerogels as drug delivery systems (DDS) has gained increased interest during the last decade since these structures have large surface area and accessible pores allowing for high drug loadings. Being biocompatible, biodegradable and presenting low toxicity, polysaccharide-based aerogels are an attractive carrier to be applied in pharmaceutical industry. Moreover, some polysaccharides (e.g. alginate and chitosan) present mucoadhesive properties, an important feature for mucosal drug delivery. This feature allows to extend the contact of DDS with biological membranes, thereby increasing the absorption of drugs through the mucosa. Alginate-based hybrid aerogels in the form of microparticles (<50MUm) were investigated in this work as carriers for mucosal administration of drugs. Low methoxyl pectin and kappa-carrageenan were co-gelled with alginate and further dried with supercritical CO2 (sc-CO2). Spherical mesoporous aerogel microparticles were obtained for alginate, hybrid alginate/pectin and alginate/kappa-carrageenan aerogels, presenting high specific surface area (370-548m(2)g(-1)) and mucoadhesive properties. The microparticles were loaded with ketoprofen via adsorption from its solution in sc-CO2, and with quercetin via supercritical anti-solvent precipitation. Loading of ketoprofen was in the range between 17 and 22wt% whereas quercetin demonstrated loadings of 3.1 5.4wt%. Both the drugs were present in amorphous state. Loading procedure allowed the preservation of antioxidant activity of quercetin. Release of both drugs from alginate/kappa-carrageenan aerogel was slightly faster compared to alginate/pectin. The results indicate that alginate-based aerogel microparticles can be viewed as promising matrices for mucosal drug delivery applications. PMID- 27393564 TI - Independent AMP and NAD signaling regulates C2C12 differentiation and metabolic adaptation. AB - The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling. AICAR showed no effect on NAD pool or nampt expression but significantly reduced histone H3 acetylation and GLUT1, cytochrome C oxidase subunit 2 (COX2), and MYH3 expression. In contrast, NMN supplementation for 24 h increased NAD pool by 45 % but did not reduce histone H3 acetylation nor promote mitochondrial gene expression. The combination of AMP and NAD signaling did not induce further metabolic adaptation, but NMN ameliorated AICAR-induced myotube reduction. We interpret these results as indication that AMP and NAD contribute to C2C12 differentiation and metabolic adaptation independently. PMID- 27393565 TI - Protein Carbonylation in Human Smokers and Mammalian Models of Exposure to Cigarette Smoke: Focus on Redox Proteomic Studies. AB - SIGNIFICANCE: Oxidative stress is one mechanism whereby tobacco smoking affects human health, as reflected by increased levels of several biomarkers of oxidative stress/damage isolated from tissues and biological fluids of active and passive smokers. Many investigations of cigarette smoke (CS)-induced oxidative stress/damage have been carried out in mammalian animal and cellular models of exposure to CS. Animal models allow the investigation of many parameters that are similar to those measured in human smokers. In vitro cell models may provide new information on molecular and functional differences between cells of smokers and nonsmokers. Recent Advances: Over the past decade or so, a growing number of researches highlighted that CS induces protein carbonylation in different tissues and body fluids of smokers as well as in in vivo and in vitro models of exposure to CS. CRITICAL ISSUES: We review recent findings on protein carbonylation in smokers and models thereof, focusing on redox proteomic studies. We also discuss the relevance and limitations of these models of exposure to CS and critically assess the congruence between the smoker's condition and laboratory models. FUTURE DIRECTIONS: The identification of protein targets is crucial for understanding the mechanism(s) by which carbonylated proteins accumulate and potentially affect cellular functions. Recent progress in redox proteomics allows the enrichment, identification, and characterization of specific oxidative protein modifications, including carbonylation. Therefore, redox proteomics can be a powerful tool to gain new insights into the onset and/or progression of CS related diseases and to develop strategies to prevent and/or treat them. Antioxid. Redox Signal. 26, 406-426. PMID- 27393567 TI - Clinical Significance of Extramural Tumor Deposits in the Lateral Pelvic Lymph Node Area in Low Rectal Cancer: A Retrospective Study at Two Institutions. AB - BACKGROUND: The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer. METHODS: This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses. RESULTS: Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P < 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P < 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001). CONCLUSIONS: The LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area. PMID- 27393568 TI - Transarterial Chemoembolization for Metastatic Neuroendocrine Tumors With Massive Hepatic Tumor Burden: Is the Benefit Worth the Risk? AB - BACKGROUND: Neuroendocrine tumors (NETs) have a propensity to metastasize to the liver, often resulting in massive tumor burden and hepatic dysfunction. While transarterial chemoembolization (TACE) is effective in treating patients with NET metastatic to the liver, there are limited data on its utility and benefit in patients with large hepatic involvement. The aim of our study was to determine the clinical benefit and complication rate of TACE in patients with massive hepatic tumor burden. METHODS: Medical records were reviewed in patients with grade 1 or 2 NETs with hepatic metastasis at our institution from January 2000 to September 2014 who underwent TACE. Of 201 total patients, 68 had massive hepatic tumor burden involving >75 % of liver parenchyma. RESULTS: Carcinoid syndrome was present in 40 (59 %) patients, and 57 (84 %) of the 68 patients were symptomatic from their disease. Complications beyond post-TACE syndrome occurred in 21.7 % of patients, with the most common complication being cardiac arrhythmias. The 30-day mortality rate was 7 %. Biochemical response was observed in 78 % of patients, while symptomatic relief and radiographic response was achieved in 85 and 82 % of patients, respectively. Median overall survival following TACE was 28 months, with 1-, 2-, and 5-year overall survival of 76, 54, and 26 %, respectively. CONCLUSIONS: In spite of massive tumor burden, clinical and biochemical improvements were seen in the majority of patients. Morbidity was acceptable and reversible but with a fairly high mortality rate of 7 %. TACE should still be considered in selective patients with massive hepatic tumor burden from metastatic NET for symptom control and palliation. PMID- 27393569 TI - Symptomatic Axillary Seroma after Sentinel Lymph Node Biopsy: Incidence and Treatment. AB - BACKGROUND: Postoperative seroma is a nuisance for patients and surgeons. Few studies investigate predisposing factors for axillary seroma after sentinel lymph node biopsy (SLNB). We sought to quantitate the risk of symptomatic seroma and characterize interventions. METHODS: We performed a retrospective review of 667 women undergoing breast-conserving surgery and SLNB at our institution between July 2007 and January 2015. Surgeons dissected sharply or with standard electrocautery. We correlated patient and tumor characteristics with symptomatic seroma using logistic regression models for univariate and multivariate predictors. All statistical tests were two sided, with p < 0.05 considered significant. RESULTS: Overall, 127 (19 %) of 667 women had axillary seromas and 98 (77 %) of 127 required further intervention for symptom relief. Seroma patients were similar in age, BMI, race, tumor type, T and N stage, and number of nodes removed as those without (all p > 0.07). Seroma rates did not vary according to surgeon, nodal mapping technique, or axillary closure technique (p = 0.8789). Multivariate analysis identified diabetes, smoking, and SSI as predictors of symptomatic axillary seroma with odds ratio of 1.97, 1.98, and 37.19 (all p < 0.017), respectively. Among the 98 of 127 patients with seroma, most (81 of 98, 83 %) resolved with a mean of 1.3 aspirations. The remainder resolved after axillary drain (13 of 98, 13 %) or additional surgery (4 of 98, 4 %). CONCLUSIONS: Symptomatic axillary seroma occurs in 14 % patients undergoing breast-conserving surgery with SLNB and is not influenced by tumor, nodal mapping, or surgeon characteristics. Management infrequently requires more than simple aspiration. Drain placement at initial surgery may be considered in smokers or patients with diabetes. PMID- 27393571 TI - Vascularity of Intrahepatic Cholangiocarcinoma on Computed Tomography is Predictive of Lymph Node Metastasis. AB - BACKGROUND: The indications for lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC) are controversial. METHODS: Seventy patients with mass forming dominant ICC underwent hepatectomy with systematic LND or lymph node sampling between 2003 and 2013. We defined the computed tomography (CT) ratio as the CT value (Hounsfield units) of the tumor divided by the CT value (Hounsfield units) of the liver parenchyma in the late arterial phase, and investigated the indications for LND with hepatectomy for ICC. RESULTS: A multivariate analysis identified lymph node metastasis (LNM; n = 19, p = 0.012) and perineural invasion (p = 0.017) as independent predictors of survival. The median survival time and 5 year survival rate in patients exhibiting LNM were 31.1 months and 16.0 %, respectively. In a subgroup analysis of patients without LNM, overall survival was comparable between patients treated with LND and those treated without LND (p = 0.801). A multivariate analysis of the preoperatively measurable parameters revealed that a CT ratio <0.88 and macroscopic periductal infiltration were independently associated with LNM. We developed a score predicting LNM of mass forming dominant ICC (LMIC score), assigning 1 point for each of these risk factors. The percentages of patients with LNM with an LMIC score of 0, 1, or 2 points were 0, 35, and 58 %, respectively. CONCLUSIONS: The vascularity of ICC is associated with important prognostic factors, LNM, and perineural invasion. LN dissection would be conducted in patients with an LMIC score of one or two points but can be omitted in patients with an LMIC score of zero. PMID- 27393570 TI - Intraoperative Sentinel Lymph Node Evaluation: Implications of Cytokeratin 19 Expression for the Adoption of OSNA in Oral Squamous Cell Carcinoma. AB - BACKGROUND: Intraoperative analysis of sentinel lymph nodes would enhance the care of early-stage oral squamous cell carcinoma (OSCC). We determined the frequency and extent of cytokeratin 19 (CK19) expression in OSCC primary tumours and surrounding tissues to explore the feasibility of a "clinic-ready" intraoperative diagnostic test (one step nucleic acid amplification-OSNA, sysmex). METHODS: Two cohorts were assembled: cohort 1, OSCC with stage and site that closely match cases suitable for sentinel lymph node biopsy (SLNB); cohort 2, HNSCC with sufficient fresh tumour tissue available for the OSNA assay (>50 mg). CK19 assays included qRT-PCR, RNA in situ hybridisation (ISH), and immunohistochemistry (IHC), as well as OSNA. RESULTS: CK19 mRNA expression was detected with variable sensitivity, depending on method, in 60-80% of primary OSCC tumours, while protein expression was observed in only 50% of tumours. Discordance between different techniques indicated that OSNA was more sensitive than qRT-PCR or RNA-ISH, which in turn were more sensitive than IHC. OSNA results showed CK19 expression in 80% of primary cases, so if used for diagnosis of lymph node metastasis would lead to a false-negative result in 20% of patients with cervical lymph node metastases. CONCLUSIONS: OSNA in its current form is not suitable for use in OSCC SLNB due to inadequate expression of the CK19 target in all case. However, the same assay technology would likely be very promising if applied using a more ubiquitous squamous epithelial target. PMID- 27393566 TI - Functional Disability in Mild Cognitive Impairment: A Systematic Review and Meta Analysis. AB - Accumulating evidence suggests that the pre-dementia syndrome mild cognitive impairment (MCI) is characterized by decrements in instrumental activities of daily living (IADL). The current review was a quantitative synthesis of the available literature to objectively characterize IADL disability in MCI while clarifying inconsistencies in findings across studies. It was hypothesized that individuals with MCI would display significantly greater functional impairment relative to cognitively intact controls. Candidate moderators specified a priori included functional assessment approach, MCI subtype, depressive symptoms, and language conducted. Online databases (PubMed/MEDLINE and PsycINFO) and reference lists were searched to identify peer-reviewed publications assessing IADL in MCI compared to normal aging. A total of 151 effect sizes derived from 106 studies met inclusionary criteria (N = 62,260). Random effects models yielded a large overall summary effect size (Hedges' g = 0.76, 95 % confidence interval: 0.68 - 0.83, p < .001) confirmed in multi-level analyses adjusted for nesting of effect sizes within studies (g = 0.78, 95 % confidence interval: 0.69 - 0.87). Functional assessment strategy and MCI subtype were significant moderators of effect size, whereas depressive symptoms and language were not. Results convincingly demonstrate that MCI is associated with significant difficulties in the performance of complex everyday tasks. It appears that functional decline, like cognitive decline, exists on a continuum from healthy aging to dementia onset. Implications for clinical practice and research priorities are discussed. PMID- 27393573 TI - Prophylactic "First-Step" Central Neck Dissection (Level 6) Does Not Increase Morbidity After (Total) Thyroidectomy. AB - BACKGROUND: In terms of morbidity, prophylactic central neck dissection (CND; level 6) in potentially malignant thyroid disease is discussed controversially. The rates of (transient and permanent) hypoparathyroidism and palsy of the recurrent laryngeal nerve (RLN) after "first-step" (FS-)CND are analyzed in this study. METHODS: Bilateral and unilateral FSCND, i.e., lymph node dissection along the RLN before (total) thyroidectomy, was performed bilaterally in 68 (group 1) and unilaterally in 44 patients (group 2), respectively. The rates of hypoparathyroidism and palsy of the RLN were documented prospectively and were compared to 237 patients of group 3 (controls) who underwent (total) thyroidectomy only. RESULTS: Fifteen of 68 patients (22 %) of group 1 developed transient and one patient had permanent hypoparathyroidism. Transient unilateral palsy of the RLN was observed in ten patients (15 %); none were permanent. Transient hypoparathyroidism was monitored in 10 of 44 patients (23 %) of group 2 and permanent hypoparathyroidism in 1 (2 %). Six patients (14 %) developed temporary palsy of the RLN; one remained permanent. Palsy was seen in 3 patients on the contralateral side of unilateral FSCND. Transient and permanent hypoparathyroidism was observed in 50 (21 %) and 2 (1 %) of 237 controls. Transient palsy of the RLN was documented in 22 (9 %) of 237 controls and permanent palsy of the RLN in 4 (2 %). CONCLUSIONS: In this single-center series, the overall permanent morbidity was low (1 %). Therefore, FSCND may be recommended (even prophylactically) for experienced high-volume surgeons in patients with thyroid nodules suspicious for malignancy. PMID- 27393572 TI - Posttreatment Surveillance in Patients with Prolonged Disease-Free Survival After Resection of Colorectal Liver Metastasis. AB - INTRODUCTION: Posttreatment surveillance protocols most often endure for 5 years after resection of colorectal liver metastasis (CRLM). Most recurrences happen within 3 years after surgical removal of the tumour. This study analysed the need of surveillance for patients with at least 3 years of disease-free survival after potentially curative resection of CRLM. METHODS: A single-centre, retrospective analysis of all consecutive patients who underwent treatment for CRLM with curative intent between 2000 and 2011. RESULTS: In total, 152 of 545 patients (28 %) remained disease-free for 3 years after successful resection of the CRLM. The estimated recurrence rate after 10 years of follow-up in this group of 152 patients was 27 %. More than half of these patients (55 %) could be treated with curative intent for their recurrences. Multivariable analysis revealed that the nodal status of the primary tumour is of significant prognostic value for developing recurrences after 3 years of disease-free survival. A disease-free interval of less than 12 months between resection of primary tumour and detection of CRLM shows a trend towards significance. Both factors were used to create a risk score, showing that patients with a low-risk profile (node-negative status and a disease-free interval <12 months) have an estimated recurrence rate of 5 % and might not benefit from intensive surveillance beyond 3 years of follow-up without a recurrence. CONCLUSIONS: The currently developed risk score shows that follow-up can be stopped in a specific subgroup 3 years after treatment for their CRLM with curative intent. PMID- 27393574 TI - Targeting Mac-1-mediated leukocyte-RBC interactions uncouples the benefits for acute vaso-occlusion and chronic organ damage. AB - Vaso-occlusive crisis (VOC) is one of the most common complications of sickle cell disease (SCD). Recurrent episodes of VOC may cause irreversible organ damage and early mortality in patients with SCD. Emerging evidence suggests that VOC arises from a complex cascade that involves interactions among multiple blood and endothelial cells in the vasculature. Previous studies have identified alphaMbeta2 integrin (Mac-1) as a critical molecule that mediates heterotypic interactions between red blood cells (RBCs) and adherent leukocytes and promotes VOC in SCD mice. Here, we show that RBC-leukocyte interactions are significantly diminished in Mac-1-deficient SCD mice, leading to an improvement of blood flow rates and prolonged survival time in a tumor necrosis factor-alpha and surgical trauma-induced VOC model. Mac-1-deletion, however, was not sufficient to reduce SCD-related chronic organ damage. Our results thus suggest uncoupled mechanisms between acute VOC benefits and the long-term complications of SCD that should be considered in future clinical trials. PMID- 27393576 TI - Sensitivity to change of the Dermatology Life Quality Index in adult females with facial acne vulgaris: a validation study. AB - BACKGROUND: The postadolescent form of acne papulopustulosa, also referred to as 'acne tarda' can have substantial negative impact on Quality of Life, especially in adult female patients. OBJECTIVE: Although the Dermatology Life Quality Index (DLQI) is widely used, empirical evidence about its performance in adult female acne patients is lacking. METHODS: In this prospective cohort study, we have investigated the sensitivity to change of the DLQI in 53 female adult acne patients with mild to moderate facial acne treated with azelaic acid (AzA) 15% gel twice daily over 24 weeks. RESULTS: Mean Investigator Static Global Assessment (ISGA) score was 2.3 (SD 0.5) at baseline and ranged from 0.9 (SD 0.3) to 2.1 (SD 0.4) at the end of the study in the 'Highly Improved' and 'Unchanged' responder groups respectively. The mean baseline DLQI score was 5.1 (SD 4.2). The Effect Size in the responder group 'Highly Improved' was 0.66; in group 'Improved' 0.62 and 0.23 in group 'Unchanged'. At the end of study, the mean DLQI score ranged from 1.1 (SD 1.5) in the 'Highly Improved' group to 3.7 (SD 6.0) in the 'Unchanged' group. CONCLUSION: The results support the sensitivity to change of the DLQI in this population. PMID- 27393575 TI - Immunoglobulin G genotypes and the risk of schizophrenia. AB - Genes of the immune system are relevant to the etiology of schizophrenia. However, to our knowledge, no large-scale studies, using molecular methods, have been undertaken to investigate the role of highly polymorphic immunoglobulin GM (gamma marker) genes in this disorder. In this investigation, we aimed to determine whether particular GM genotypes were associated with susceptibility to schizophrenia. Using a matched case-control study design, we analyzed DNA samples from 798 subjects-398 patients with schizophrenia and 400 controls-obtained from the U.S. National Institute of Mental Health Repository. GM alleles were determined by the TaqMan((r)) genotyping assay. The GM 3/3; 23-/23- genotype was highly significantly associated with susceptibility to schizophrenia (p = 0.0002). Subjects with this genotype were over three times (OR 3.4; 95 % CI 1.7 6.7) as likely to develop schizophrenia as those without this genotype. Our results show that immunoglobulin GM genes are risk factors for the development of schizophrenia. Since GM alleles have been implicated in gluten sensitivity and in immunity to neurotropic viruses associated with cognitive impairment, the results presented here may help unify these two disparate areas of pathology affected in this disorder. PMID- 27393577 TI - Nursing Diagnosis for People With Heart Failure Based on the Hemodynamic Profiles. AB - OBJECTIVE: To investigate the association of nursing diagnoses (NDs) identified for patients with heart failure (HF) based on their hemodynamic profiles. METHOD: Analytical, cross-sectional study conducted in the emergency room of a public hospital in a large cardiology center in Brazil. One hundred medical records of patients with HF whose hemodynamic profile had been established were analyzed. RESULTS: The main NDs identified were risk of infection, bathing self-care deficit, risk for decreased cardiac output, risk for falls, and excess fluid volume. There was no statistically significant difference (p > .05) between the different hemodynamic profiles and the ND found. CONCLUSION AND IMPLICATIONS: Nurses need to develop skills for improving their diagnostic abilities to ensure implementation of consistent interventions. PMID- 27393578 TI - Alterations in geometry, biomechanics, and mineral composition of juvenile rat femur induced by nonplanar PCB-155 and/or planar PCB-169. AB - Exposure to widespread lipophilic and bioaccumulative polychlorinated biphenyls (PCBs) induces diverse biochemical and toxicological responses in various organs, including the bone. The aim of this study was to evaluate the changes in growth rate, geometry, serum, and bone biochemical parameters and biomechanics of juvenile rat femur induced by lactational exposure to nonplanar PCB-155 and planar PCB-169 individually and in combination. Fifteen lactating Wistar rats were divided into four groups (PCB-169, PCB-155, PCB-155+169, and control), and PCBs were administered intraperitoneally at different time points after delivery. Femurs from 22-day-old offspring were analyzed by microCT, three-point bending test and inductively coupled plasma-mass spectrometry (ICP-MS) to obtain data on bone geometry, biomechanics and mineral composition. The serum levels of calcium, phosphate and alkaline phosphatase were also determined. Lactational exposure to planar PCB-169 resulted in shorter and thinner femurs, reduced endosteal and periosteal perimeters, smaller total cross-sectional and medullary areas, and lowered serum bone marker levels and calcium levels in the bone, while femur mechanical properties were not significantly altered. The changes observed in the combination exposure (PCB-155+169) group were similar to those observed in the PCB-169 group but were less pronounced. In summary, our results demonstrate that alterations in lactationally exposed offspring were primarily induced by planar PCB-169. The milder outcome in the combined group suggested that the PCB-169 mediated toxic effects on the bone might be reduced by a nonplanar PCB-155 congener. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1135-1146, 2017. PMID- 27393579 TI - Adjuvant Antiangiogenic Treatment for Aggressive Giant Cell Lesions of the Jaw: A 20-Year Experience at Massachusetts General Hospital. AB - PURPOSE: To document long-term outcomes using a standardized treatment protocol of enucleation with preservation of vital structures and adjuvant subcutaneous interferon for aggressive giant cell lesions (GCLs) of the jaws. MATERIALS AND METHODS: A retrospective cohort study was designed. We evaluated all patients treated at Massachusetts General Hospital from April 1995 through September 2015 by enucleation with preservation of vital structures and adjuvant daily subcutaneous interferon for aggressive GCLs. The sample included patients with complete medical records consisting of clinical, radiographic, histopathologic, and follow-up data. The exclusion criteria included patients with incomplete records, contraindications to interferon therapy, non-aggressive GCLs, and GCLs associated with syndromes or with hyperparathyroidism. The primary outcome variable was long-term progression-free survival (PFS). The secondary outcome variables were adverse effects and laboratory abnormalities classified by type, frequency, and severity. Predictor variables for recurrence or failure included age, gender, location and features of lesion, type of procedure, duration of interferon treatment, amount of bone fill at end of treatment, and adverse effects. Descriptive statistics, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were computed. RESULTS: Of a total of 77 patients, 45 (mean age, 18.8 +/- 12.5 years; 29 female patients; 36 in whom the mandible was affected) met the inclusion criteria. The mean duration of interferon therapy was 7.9 +/- 2.3 months. After follow-up of 4.8 +/- 3.9 years, 6 patients showed progression of the lesion, considered recurrence (13.3% failure rate, 82.6% PFS rate). Most patients had mild (n = 42; 93.3%) and/or moderate (n = 31; 68.8%) side effects, which were readily managed. Adverse effects required stoppage of interferon in 7 patients, whereas no patients had long-term toxicity. No variable was significantly associated with PFS. CONCLUSIONS: The results of this study indicate that enucleation with preservation of vital structures in combination with adjuvant interferon alfa is a reliable treatment for aggressive GCLs of the jaws associated with a low recurrence rate. PMID- 27393580 TI - Metastatic Melanotic Neuroectodermal Tumor of Infancy: Report of a Case and Review of the Literature. AB - Melanotic neuroectodermal tumors of infancy (MNTI) are rapidly growing pigmented tumors that occur predominantly within bony head and neck structures. There are fewer than 400 cases reported in the literature with the majority affecting the maxilla. Locations in other intraosseous and extraosseous structures have been characterized, including the mandible (6% of MNTIs). Infants in the first year of life are primarily affected. Surgical resection is the primary treatment modality with and without adjuvant chemotherapy for malignant tumors, which comprise less than 25 cases in the literature, and of metatstatic mandibular tumors, which has only been documented in one other case. The purpose of this investigation is to review associated literature and present a case highlighting treatment considerations of a metastatic mandibular MNTI. We present the case of a six month old boy with a rapidly growing bluish mass of the right mandible. Preoperatively incisional biopsy led to a diagnosis of MNTI and subsequent surgical planning involved hemimandibulectomy from the right mandibular condyle to the left posterior body region with one centimeter margins. At the time of initial surgery, enlarged lymph nodes removed from the neck demonstrated abnormality consistent with metastatic spread of the tumor. Islands of tumor cells were noted: small, round, bluestaining cells resembling neuroblasts with mitotic activity as well as pigmented cells containing melanin. Because of regional node metastasis, chemotherapy was completed following surgery. The patient recovered and was followed without evidence of recurrence. At 3.5 years postresection, a secondary reconstruction was completed using a fibula osteocutaneous free flap combined with a costochondral rib graft. In reviewing similar cases of malignant MNTI reported in the literature, a search of the MEDLINE database until 2014 was performed. These were evaluated based on management type and outcome, including surgical and chemotherapeutic treatments and the incidence of recurrence or metastasis. PMID- 27393582 TI - Correlation between NaCl Sensitivity of Rhizobium Bacteria and Ineffective Nodulation of Leguminous Plants. AB - A sodium chloride (NaCl)-sensitive mutant of Rhizobium fredii USDA191, which contained a single copy of Tn5-Mob transposed into chromosomal DNA, was obtained by Tn5-Mob random insertion. The growth rate of this mutant was lower than that of the wild type in the presence of 0.2 M NaCl and it seemed to lack the inductive ATP production in response to the addition of NaCl. This mutant induced the formation of small and whitish nodules on lateral roots of soybeans, which were negative for acetylene reduction activity, indicating that the nodules were ineffective for nitrogen fixation. The mutant also reduced the weight of above ground portions and roots to 64 and 55%, respectively, compared with the weight of the plants inoculated with the wild-type cells. These results suggest that NaCl sensitivity of Rhizobium bacteria is one of the important factors for nodule formation and nitrogen fixation. PMID- 27393581 TI - Sodium Zirconium Cyclosilicate (ZS-9): A Novel Agent for the Treatment of Hyperkalemia. AB - Hyperkalemia is a potentially life-threatening electrolyte abnormality that may be caused by select medications, underlying organ dysfunction, or alterations in potassium homeostasis. Treatment for this condition has remained largely unchanged since the release of sodium polystyrene sulfonate (SPS) in 1958. Despite its widespread use, the safety and efficacy of SPS remains controversial. Two novel potassium-binding resins have emerged in recent years. Patiromer was the first of these to receive U.S. Food and Drug Administration approval for the treatment of hyperkalemia in October 2015. A second potassium-binding resin, a zirconium cyclosilicate currently known as ZS-9, may provide yet another alternative to the archetypal treatment with SPS. ZS-9 is an orally administered nonabsorbed inorganic compound that selectively binds potassium ions in vivo. Two phase III multicenter, randomized, placebo-controlled, double-blind trials have evaluated ZS-9 for the treatment of acute hyperkalemia. In this review, we discuss the pharmacology, clinical efficacy, safety, and potential place in therapy of ZS-9 for the enhanced elimination of potassium in the setting of hyperkalemia. PMID- 27393583 TI - A Novel Catechol Oxidase Enzyme Electrode for the Specific Determination of Catechol. AB - An enzyme electrode for the specific determination of catechol was developed by using catechol oxidase (EC 1.10.3.1) from eggplant (Solanum melangena L.) in combination with a dissolved oxygen probe. Optimization studies of the prepared catechol oxidase enzyme electrode established a phosphate buffer 50 mM at pH 7.0 and 35 degrees C to provide the optimum conditions for affirmative electrode response. The enzyme electrode response depended linearly on a catechol concentration range of 5*10(-7)-30*10(-5) M with a response time of 25 sec and substrate specificity of the catechol oxidase electrode of 100%. The biosensor retained its enzyme activity for at least 70 days. PMID- 27393584 TI - Penicillin and D-Alanyl-D-alanine Accelerate Spore Formation of Myxococcus xanthus Subcultured Cells. AB - In repetitive subcultures of Myxococcus xanthus cells, addition of penicillin to the developmental medium accelerated the appearance of the fruiting bodies and spore formation. During development of M. xanthus, DD-carboxypeptidase, which functions in the regulation of the level of cross-linkage, was also induced by penicillin. When D-alanyl-D-alanine, the structure of which is similar to the beta-lactam structure of penicillin, was added to the developmental medium, 0.3 to 0.6 mM D-alanyl-D-alanine accelerated spore formation strongly. The activity of D-alanyl-D-alanine ligase, which synthesizes D-alanyl-D-alanine from D alanine, increased gradually with maximum activity observed at the initial stage of sporulation. These results raise the hypothesis that M. xanthus produces and releases D-alanyl-D-alanine during development, and the released D-alanyl-D alanine may function as an inducer of sporulation. PMID- 27393585 TI - Novel Oxidized Sorbicillin Dimers with 1,1-Diphenyl-2-picrylhydrazyl-Radical Scavenging Activity from a Fungus. AB - Three yellowish compounds with 1,1-diphenyl-2-picrylhydrazyl-radical scavenging activity were newly isolated from the fermentation broth of Trichoderma sp. USF 2690 strain that had been isolated from a soil sample: two were novel oxidized sorbicillin dimers designated as bisorbibutenolide (1) and bisorbicillinolide (2), and one was sorbicillin (3) itself. The structures of 1 and 2 were determined from spectroscopic evidence. In the DPPH-radical scavenging assay, alpha-tocopherol gave an ED50 value of 17.0 MUM after standing for 30 min, while continuing observation showed that the ED50 values for bisorbibutenolide, bisorbicillinolide, and sorbicillin slowly reached 80.8, 88.8 and 152.3 MUM over 24 hr. PMID- 27393586 TI - Leaf-opening Substance in the Nyctinastic Plant, Albizzia julibrissin Durazz. AB - cis-p-Coumaroylagmatine (1) was isolated from Albizzia julibrissin Durazz, a nyctinastic plant, as a leaf-opening substance. The compound was quite effective for opening the plant leaves at 5*10(-6) M at night, but was not effective for other nyctinastic plants. The bioactive fraction with leaf-closing activity was also separated from the plant extract. Although the leaf-opening activity of the plant extract changed between the day and night, the content of 1 was almost constant through a 24-h day. These results suggest that the change in content of an unknown leaf-closing factor induced balance between the two leaf-movement factors through a 24-h day. PMID- 27393587 TI - Substrate Specificity of Aqualysin I, a Bacterial Thermophilic Alkaline Serine Protease from Thermus aquaticus YT-1: Comparison with Proteinase K, Subtilisin BPN' and Subtilisin Carlsberg. AB - Aqualysin I is the alkaline serine protease isolated from an extreme thermophile, Thermus aquaticus YT-1. We analyzed kinetic properties of aqualysin I, using sixteen kinds of chromogenic succinyl-tripeptide p-nitroanilides as substrates. And we compared the substrate specificity of aqualysin I with those of proteinase K, subtilisin BPN', and subtilisin Carlsberg. We found that aqualysin I had three subsites, S1, S2, and S3, in the substrate binding site. S1 site preferred alanine and phenylalanine. S2 site preferred alanine and norleucine. And S3 site preferred phenylalanine and isoleucine. These specificities were similar to those of proteinase K and subtilisin BPN'. The specificity of subtilisin Carlsberg differed from those of other enzymes. PMID- 27393588 TI - Formation of Inclusion Complexes of Cycldextrin with Ethanol under Anhydrous Conditions. AB - Complex formation of poorly water soluble organic compounds with cyclodextrin (CD) is quite difficult in an aqueous cyclodextrin system. Formation of the inclusion complex of d-limonene, phenyl ethanol, acetophenone, or menthol was investigated in a slurry form of alpha-, beta-, or gamma-CD in organic solvents or alcohol under anhydrous conditions. Ethanol and methanol were found to be good solvents for this method. The use of ethanol as the solvent was investigated in greater detail. There existed an optimal amount of ethanol for the maximum inclusion of d-limonene as the guest compound. However, an excess of ethanol inhibited the inclusion. An adsorption model of alcohol on CD, analogous to the substrate inhibition model of enzyme kinetics, could correlate the inclusion ratio with the amount of alcohol added to CD. PMID- 27393589 TI - Enantioselective Herbicidal Activity of Chiral alpha-Methylbenzylphenylureas against Cyperaceae and Echinochloa Paddy Weeds. AB - Optically active alpha-methylbenzylphenylureas were synthesized and tested for their herbicidal activities against barnyardgrass and Cyperaceae paddy weeds in a greenhouse to evaluate the cross intergenus phytotoxicity between rice and barnyardgrass and the enantioselective phytotoxicity to the weeds. Several compounds controlled the growth of the weeds, and a suitable enantiomer for successful weed control was dependent on the type of weed and on the substituent at the aniline moiety. The (R)-2-isoPr and (R)-2-tert-Bu derivatives significantly controlled barnyardgrass and both annual and perennial Cyperaceae paddy weeds. The (R)-2-Et and (R)-2-CF3 derivatives showed the strong herbicidal activity against perennial Cyperaceae paddy weeds, while the (S)-enantiomers of the unsubstituted and fluoro derivatives were active against barnyardgrass. The enantioselectivity of the most potent compounds was high. PMID- 27393590 TI - Effects of High-Voltage Electric Field Treatment on Bread Starch. AB - Bread dough was subjected to a high-voltage electric field (HVEF) during the first fermentation, and the bread firmness and the crystallinity of the starch (intensity of diffraction peak at 17.08 degrees 2theta assigned to 4a; 5.24 A d spacing) isolated from the breads, which had been stored at 4 and 20 degrees C, were examined. The HVEF treatment had the effects of reducing the bread firming at both storage temperatures as compared to the untreated bread. In this study, unexpected results were obtained for the crystallinity in the HVEF treated bread starches: while the firmness of the treated bread increased considerably after the first 3 days of storage at both temperatures, the rate of development in crystallinity was retarded at 20 degrees C as compared with that of the untreated bread, but the opposite effect was observed at 4 degrees C; that is, storing the bread at 4 degrees C, the treated bread starch increased in crystallinity. These findings strongly suggest that crumb firming of the bread is involved in its water retention ability, taking into account the fact that the HVEF treatment made it possible to maintain bread softness longer than was possible for untreated bread. We, therefore, concluded that the increase in bread firmness was not closely related to the crystallinity of the bread starch, but was more influenced by the storage temperature. PMID- 27393591 TI - Purification and Characterization of Cu, Zn Superoxide Dismutase from Ark Shell Scapharca broughtonii. AB - A superoxide dismutase has been purified to apparent homogeneity from the muscular tissue of the ark shell, Scapharca broughtonii, by ammonium sulfate fractionation, and consecutive column chromatographies using DEAE-Sephadex and Sephadex G-100. This enzyme has a molecular weight of 71,700 and is composed of two identical subunits of M r 35,800, which are joined by noncovalent interactions. The purified enzyme was stable over the range of pH 5.0-10.0 at 4 degrees C for 24 h and at temperatures below 45 degrees C. Cyanide at 0.1 and 1 mM inhibited the activity of the superoxide dismutase 56 and 100%, but 5 mM azide caused 8% inhibition. The optical spectrum of this enzyme had a maximum at 265 nm, and the amino acid composition of the enzyme was similar to that of the other Cu, Zn superoxide dismutases except for the contents of threonine, serine, proline, and leucine. Atomic absorption spectroscopy showed that this enzyme has approximately 2 atoms of Cu(2+) and Zn(2+) per mole of enzyme. These results indicate that the purified enzyme from ark shell, Scapharca broughtonii, is a Cu, Zn superoxide dismutase. PMID- 27393592 TI - N-Carbamoyl-L-Cysteine as an Intermediate in the Bioconversion from D,L-2-Amino Delta (2)-Thiazoline-4-Carboxylic Acid to L-Cysteine by Pseudomonas sp. ON-4a. AB - We investigated the conversion of D,L-2-amino-Delta (2)-thiazoline-4-carboxylic acid (D,L-ATC) to L-cysteine with Pseudomonas sp. ON-4a, an ATC-assimilating bacterium. Cysteine and N-carbamoylcysteine (NCC), but not S-carbamoylcysteine (SCC), were produced from D,L-ATC by a cell-free extract from the strain. These products were isolated from the reaction mixture and then identified as the L form. Similar results were obtained with P. putida AJ3865 and unidentified strain TG-3, an ATC-assimilating bacteria. It became clear that L-NCC is an intermediate in the conversion of D,L-ATC to L-cysteine in these Pseudomonas strains. Furthermore, it was suggested that these bacteria have L-ATC hydrolase and L-NCC amidohydrolase. PMID- 27393593 TI - Preparation of Water and Ethanolic Extracts of Propolis and Evaluation of the Preparations. AB - Propolis was extracted using water and various concentrations of ethanol as solvents. The extracts were investigated by measurement of absorption spectrum with a UV spectrophotometer, reversed phase-high pressure thin-layer chromatography and reversed phase-HPLC. Maximum absorption of all extracts was 290 nm, resembling flavonoid compounds, and the 80% ethanolic extract showed highest absorption at 290 nm. The most isosakuranetin, quercetin, and kaempferol were extracted from mixtures of propolis and 60% ethanol, while 70% ethanol extracted the most pinocembrin and sakuranetin, but 80% ethanol extracted more kaempferide, acacetin, and isorhamnetin from propolis. The 60 to 80% ethanolic extracts of propolis strongly inhibited microbial growth and 70 and 80% ethanolic extracts had the greatest antioxidant activity and 80% ethanolic extract strongly inhibited hyaluronidase activity. PMID- 27393594 TI - Characteristics of Psychrophilic Alkaline Phosphatase. AB - The phosphatase of a psychrophile (Shewanella sp.) was purified by ammonium sulfate fractionation, followed by sequential column chromatographies. The purified enzyme was electrophoretically homogeneous on native- and SDS-PAGE. Its molecular weight was 41,826 by its amino acid composition. The enzyme had its optimal pH for the activity at 9.8, and a broad substrate specificity to dephosphorylate ATP, pyrophosphate, glycerophosphate, and so on. Its activity was increased by metal ions including Mg(2+), Mn(2+), and Co(2+). The maximal activity was observed at 40 degrees C, and the enzyme at 0 degrees C showed 39% of activity at 40 degrees C. The enzyme, however, tended to lose its activity at 20 degrees C and pH 9.8. These results indicated that purified enzyme was an alkaline phosphatase with characteristics; high catalytic efficiency at low temperature and gradual inactivation at an intermediate temperature. PMID- 27393595 TI - Fluorescent Determination of Double-stranded DNA with an Anionic 1,1' Azonaphthalene Derivative. AB - Palatine chrome black 6BN (PCB6BN) is virtually non-fluorescent in an aqueous solution or in the presence of single-stranded DNA (ssDNA), whereas the fluorescence intensity of PCB6BN was linearly enhanced up to 300 MUM of double stranded DNA (dsDNA) base pairs. PCB6BN could be a useful fluorescent probe for quantifying dsDNA even when ssDNA is present for both heterogeneous and homogeneous assays. PMID- 27393596 TI - Isolation and Identification of New Antifungal Macrophorins E, F and G as Malonyl Meroterpenes from Botryosphaeria berengeriana. AB - Macrophorins E, F and G were newly isolated from Botryosphaeria berengeriana, each showing potent antifungal activity similar to that of macrophorin A against phytopathogenic fungi B. berengeriana and Gibberella fujikuroi. Macrophorins E and G were identified as novel malonylated derivatives of macrophorin A, and F as a macrophorin E congener with a hydroxy-cyclohexenedione moiety instead of its epoxy-cyclohexenone one. PMID- 27393597 TI - A Newly Rearranged 2(3->20)Abeotaxane Diterpene from the Bark of Chinese Yew, Taxus mairei. AB - A newly rearranged 2(3->20)abeotaxane diterpenoid with a unique 6/10/6 skeleton was isolated from the bark of the Chinese yew, Taxus mairei. The structure was established as being 7beta,13alpha-diacetoxy-2alpha,5alpha,10beta-trihydroxy-9 keto-2(3->20)abeotaxane on the basis of 1-D and 2-D NMR data. The relative stereochemistry was defined from the results of a NOESY experiment. This is the first reported isolation of a rearranged 2(3->20)abeotaxane from Taxus mairei. PMID- 27393598 TI - Energy Dispersive X-Ray Microanalysis of Element Distribution in Amaranth Seed. AB - Energy dispersive X-ray microanalysis in combination with scanning electron microscopy was used to examine the distribition of mineral nutrients in amaranth seed. It was found that P, K, and Mg were exclusively localized in embryonic tissue (cotyledons and radicles), but not in procambium. Since phytin globoids occur in cotyledons and radicles in the seed, it is conceived that these elements are associated with phytate. Sulfur was evenly distributed in the embryonic tissue including procambium, which might be derived from sulfur-containing proteins. Calcium was mostly present in seed coats and the boundary between the perisperm and embryo, suggesting that Ca is associated with pectins that constitute the network structure of cell wall. PMID- 27393599 TI - Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base. AB - BACKGROUNDS AND OBJECTIVES: Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB). METHODS: Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference. RESULTS: Patients with MBC (n = 3,688), AMCB (n = 288), and IDC (n = 918,870) met inclusion criteria. Comparing MBC with AMCB, the mean age at diagnosis (52.9 vs. 53.9 years), mean tumor size (2.4 vs. 2.5 cm), lymph node positivity (22.8% vs. 22.4%), estrogen receptor (ER) positivity (22% vs. 25%), progesterone receptor (PR) positivity (14% vs. 15%), HER2 positivity (11% vs. 14%), rate of breast conserving surgery (67% vs. 68%), use of chemotherapy (76% vs. 75%), and use of hormonal therapy (19% vs. 18%), respectively, were not clinically or statistically different. Five-year (92% vs. 89%) and 10-year survival rates (85% vs. 87%) were not significantly different (P = 0.46). CONCLUSIONS: There does not appear to be any reason to differentiate between AMCB and MBC given the similarities in presentation, treatment and prognosis. J. Surg. Oncol. 2016;114:533-536. (c) 2016 Wiley Periodicals, Inc. PMID- 27393600 TI - Guest editorial. PMID- 27393601 TI - Natural history of diseases: Statistical designs and issues. AB - Understanding the natural history of a disease is an important prerequisite for designing studies that assess the impact of interventions, both chemotherapeutic and environmental, on the initiation and expression of the condition. Identification of biomarkers that mark disease progression may provide important indicators for drug targets and surrogate outcomes for clinical trials. However, collecting and visualizing data on natural history is challenging, in part, because disease processes are complex and evolve in different chronological periods for different subjects. Various epidemiological designs are used to elucidate components of the natural history process. We briefly discuss statistical issues, limitations, and challenges associated with various epidemiological designs. PMID- 27393602 TI - Detection and genetic characterization of hepatitis E virus (HEV) genotype 3 subtype c in wild boars in Italy. AB - Hepatitis E virus (HEV) was detected in stools collected from wild boars in Italy, with an overall prevalence of 1.5 % (3/196). The sequence of a ~3.0-kb portion at the 3' end of the genome of one such strain, HEV/WB/P6-15/ITA, was determined. In the full-length ORF2, which encodes the capsid protein, the virus was genetically closest to wild boar and human HEV strains currently classified as genotype 3 subtype c. Interestingly, the 3' end of ORF2 of the WB/P6-15/ITA matched the 340-nucleotide (nt) sequence (94.0 % nt identity) of the human strain PeGe, identified in 2015 from a patient with acute hepatitis E in Genoa, Italy, suggesting that similar HEV strains are circulating in the same geographical setting in humans and animals. PMID- 27393603 TI - Whole genomic characterization of Korean porcine G8P[7] reassortant rotaviruses. AB - This study analyzed eleven genomic segments of three Korean porcine G8P[7] group A rotavirus (RVA) strains. Phylogenetically, these strains contained two bovine like and nine porcine-like genomic segments. Eight genes (VP1, VP2, VP6 and NSP1 NSP5) of strains 156-1 and 42-1 and seven genes (VP1, VP2, VP6 and NSP2-NSP5) of strain C-1 clustered closely with porcine and porcine-like animal strains and distantly from typical human Wa-like strains. The VP3-M2 genotype of these strains clustered closely with bovine-like strains, but distantly with typical human DS-1-like strains. These data indicate that multiple reassortments involving porcine and bovine RVA strains in Korea must have occurred. PMID- 27393604 TI - BEATVIC, a body-oriented resilience training with elements of kickboxing for individuals with a psychotic disorder: study protocol of a multi-center RCT. AB - BACKGROUND: Individuals with a psychotic disorder are at an increased risk of becoming victim of a crime or other forms of aggression. Research has revealed several possible risk factors (e.g. impaired social cognition, aggression regulation problems, assertiveness, self-stigma, self-esteem) for victimization in patients with a psychotic disorder. To address these risk factors and prevent victimization, we developed a body-oriented resilience training with elements of kickboxing: BEATVIC. The present study aims to evaluate the effectiveness of the intervention. METHODS/DESIGN: Seven mental health institutions in the Netherlands will participate in this study. Participants will be randomly assigned to either the BEATVIC training or the control condition: social activation. Follow-ups are at 6, 18 and 30 months. Short term effects on risk factors for victimization will be examined, since these are direct targets of the intervention and are thought to be mediators of victimization, the primary outcome of the intervention. The effect on victimization will be investigated at follow-up. In a subgroup of patients, fMRI scans will be made before and after the intervention period in order to assess potential neural changes associated with the effects of the training. DISCUSSION: This study is the first to examine the effectiveness of an intervention targeted at victimization in psychosis. Methodological issues of the study are addressed in the discussion of this paper. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN21423535 . Retrospectively registered 30-03-2016. PMID- 27393606 TI - [Not Available]. PMID- 27393605 TI - Identification of differentially expressed genes associated with differential body size in mandarin fish (Siniperca chuatsi). AB - Body size is an obvious and important characteristic of fish. Mandarin fish Siniperca chuatsi (Basilewsky) is one of the most valuable perciform species widely cultured in China. Individual differences in body size are common in mandarin fish and significantly influence the aquaculture production. However, little is currently known about its genetic control. In this study, digital gene expression profiling and transcriptome sequencing were performed in mandarin fish with differential body size at 30 and 180 days post-hatch (dph), respectively. Body weight, total length and body length of fish with big-size were significantly higher than those with small-size at both 30 and 180 dph (P < 0.05). 2171 and 2014 differentially expressed genes were identified between small size and big-size fish at 30 and 180 dph, respectively. RT quantitative PCR (qPCR) analysis showed that the differential expression of 10 selected genes in mandarin fish that went through the same training procedure. The genes were involved in the growth hormone-insulin-like growth factor axis, cell proliferation and differentiation, appetite control, glucose metabolism, reproduction and sexual size dimorphism pathways. This study will help toward a comprehensive understanding of the complexity of regulation of body size in mandarin fish individuals and provide valuable information for future research. PMID- 27393608 TI - [Not Available]. PMID- 27393607 TI - [Not Available]. PMID- 27393609 TI - [Not Available]. PMID- 27393610 TI - [Not Available]. PMID- 27393611 TI - [Not Available]. PMID- 27393612 TI - [Not Available]. AB - A cohort is a group of individuals sharing some characteristics, followed longitudinally. Essential tools of epidemiology, these studies provide pieces of evidence of the relationship between an exposition and outcomes in order to guide public health policies. In France, many cohorts have been conducted over the past few years. Sometimes, initiated by independent research teams (e.g. E3N) but more often, either requested by health authorities in a global public health plan (e.g. MEMENTO in the Alzheimer plan) or conducted to investigate a safety issue (e.g. France Coag). Besides, post authorization studies often consist in prospective cohorts. Because of objectives, designs and governance arrangements diversity; participants questioned whether it was interesting for researchers, regulators and industrials to use this epidemiological tool. Some findings about difficulties met in cohorts' establishment have been shared by each other. In order to make cohorts more efficient, participants have made some recommendations. PMID- 27393613 TI - Spatial Epidemiology and Risk Factor Analysis of White Spot Disease in the Shrimp Farming Industry of Sinaloa, Mexico, from 2005 to 2011. AB - White spot disease (WSD), caused by the white spot syndrome virus, is currently one of the primary causes of mortality and economic losses in the shrimp farming industry worldwide. In Mexico, shrimp production is one of the most important primary activities generating an annual income of USD 711 million. However, WSD introduction in 1999 had a devastating impact for the Mexican shrimp industry. The aim of this study was to characterize the WSD spatio-temporal patterns and to identify the primary risk factors contributing to WSD occurrence from 2005 to 2011 in Sinaloa, Mexico. We used data collected by the 'Comite Estatal de Sanidad Acuicola de Sinaloa' from 2005 to 2011 regarding WSD outbreaks as well as environmental, production and husbandry factors at farm level. The spatio temporal patterns of WSD were described using space-time scan statistics. The effect of 52 variables on the time to WSD outbreak occurrence was assessed using a multivariable Cox proportional hazards model. Results reveal that WSD risk and survival time were not homogeneously distributed as suggested by the significant clusters obtained using the space-time permutation model and the space-time exponential model, respectively. The Cox model revealed that the first production cycle [hazard ratio (HR) = 11.31], changes from 1 to 1.4 degrees C of temperature oscillation caused by 'El Nino'/'La Nina' events (HR = 1.44) and high average daily growths (HR = 1.26) were significantly associated with lower survival (i.e. shorter time to WSD outbreak) on farm. Conversely, shrimp weight at the moment of the outbreak (HR = 0.159), changes from -0.9 to -0.5 degrees C of temperature oscillation caused by 'El Nino'/'La Nina' events (HR = 0.540), high superficial water temperature during the pound stocking (HR = 0.823) and high (>100) number of days of culture (HR = 0.830) were factors associated with higher survival. Results are expected to inform the design of risk-based, intervention strategies to minimize the impact of WSD in Mexico. PMID- 27393614 TI - Apheresis for collection of Ebola convalescent plasma in Liberia. AB - PURPOSE: This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. METHODS: A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital's power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. RESULTS: The bloodmobile was operational within 3 weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of ninty-nine tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; twenty-one were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; eighty-nine apheresis attempts resulted in eighty-one successful collections. CONCLUSIONS: Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians, and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety. J. Clin. Apheresis 32:175-181, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27393615 TI - Childhood fever in well-child clinics: a focus group study among doctors and nurses. AB - BACKGROUND: Fever is common in children aged 0-4 years old and often leads to parental worries and in turn, high use of healthcare services. Educating parents may have beneficial effects on their sense of coping and fever management. Most parents receive information when their child is ill but it might be more desirable to educate parents in the setting of well-child clinics prior to their child becoming ill, in order to prepare parents for future illness management. This study aims to explore experiences of well-child clinic professionals when dealing with childhood fever and current practices of fever information provision to identify starting points for future interventions. METHODS: We held four focus group discussions based on naturalistic enquiry among 22 well-child clinic professionals. Data was analysed using the constant comparative technique. RESULTS: Well-child clinic professionals regularly received questions from parents about childhood fever and felt that parental worries were the major driving factor behind these contacts. These worries were assumed to be driven by: (1) lack of knowledge (2) experiences with fever (3) educational level and size social network (4) inconsistencies in paracetamol administration advice among healthcare professionals. Well-child clinic professionals perceive current information provision as limited and stated a need for improvement. For example, information should be consistent, easy to find and understand. CONCLUSIONS: Fever related questions are common in well-child care and professionals perceive that most of the workload is driven by parental worries. The focus group discussions revealed a desire to optimise the current limited information provision for childhood fever. Future interventions aimed at improving information provision for fever in well-child clinics should consider parental level of knowledge, experience, educational level and social network and inconsistencies among healthcare providers. Future fever information provision should focus on improving fever management and practical skills. PMID- 27393616 TI - The "Ram's Horns Sign": A Case Report of an Unusual Side Effect of OnabotulinumtoxinA in a Chronic Migraine Patient. AB - OnabotulinumtoxinA (BoNT-A) has been reported as an effective prophylactic treatment for chronic migraine to reduce disease severity improving health related quality of life. However, BoNT-A, due to its activity on either the injected or adjacent muscles of the upper face, may induce well-known side effects, such as the eyebrow or eyelid ptosis. However, unusual muscular side effects, related to the neurotoxic mechanism, may also arise. We describe the clinical case of a 55-year-old male patient who has been treated for chronic migraine by the injection of BoNT-A, according to the PREEMPT protocol. Two weeks later, the patient developed two symmetrical bumps on the upper part of the forehead similar to the horns of a ram. We report, for the first time, this peculiar BoNT-A side effect and suggest that the injection of additional BoNT-A doses in the upper medial frontal fibers, for each side, can normalize the forehead shape over two weeks. PMID- 27393617 TI - Characteristics and prognosis of interval cancers after biennial screen-film or full-field digital screening mammography. AB - We determined the characteristics and prognosis of interval breast cancers (IC) at screen-film (SFM) and full-field digital (FFDM) screening mammography. The study population consisted of 417,746 consecutive screening mammograms (302,699 SFM screens and 115,047 FFDM screens), obtained between 2000 and 2011. During 2 year follow-up, we collected breast imaging reports, surgical reports, and pathology results. A total of 800 ICs had been diagnosed in the screened population, of which 288 detected in the first year (early ICs) and 512 in the second year (late ICs) after a negative screen. 31.3 % of early IC's and 19.1 % of late IC's, respectively, were visible in retrospect on the latest previous screens, but had been missed during screening (P < 0.001). Missed invasive ICs were larger (28.5 mm vs. 23.9 mm, P = 0.003) and showed a higher fraction of T3+cancers (16.9 vs. 8.5 %, P = 0.02) than true ICs (i.e., not visible at the latest screen). A higher portion of missed than true ICs underwent mastectomy (44.7 vs. 30.8 %, P = 0.002). We found no differences in mammographic and tumor characteristics for early ICs, detected either after SFM or FFDM. Late ICs following FFDM were more often true ICs than missed ICs (69.0 vs. 57.6 %, P = 0.03) and more often receptor triple negative (P = 0.02), compared to late ICs at SFM. Interval cancer subgroups showed comparable overall survival. Interval cancer subgroups show distinctive mammographic and tumor characteristics but a comparable overall survival. PMID- 27393619 TI - Patterns and determinants of receipt of follow-up mammography and/or clinical examination in a cohort of Italian breast cancer survivors. AB - Information regarding the use of mammography by breast cancer survivors is limited. This study aimed at evaluating the compliance to surveillance mammography and/or clinical breast examination and the associated factors among patients living in northern Italy. A cancer registry-based cohort of 1304 patients living in the Health Care District of Forli was followed up for 10 years. Eighty percent of patients had a mammogram and/or clinical breast examination during the first year after treatment. The proportion decreased to 67 % at 10 years of follow-up. Three demographic characteristics were independently associated with lower odds of having an annual mammogram and/or clinical breast examination: age at diagnosis [odds ratio (OR) 0.51, 95 % confidence interval (CI) 0.41-0.63 for patients aged 65-74 years; and OR 0.14, 95 % CI 0.11-0.18, for patients >=75 years versus patients aged <64 year]; socio-economic status (OR 0.81, 95 % CI 0.65-1.00, for deprived patients versus patients of the reference class); and hospital travel time greater than 30 min (OR 0.44, 95 % CI 0.29-0.68 versus <=15 min). With respect to clinical and disease characteristics, lower odds were observed for patients treated with mastectomy (OR 0.79, 95 % CI 0.65 0.97), for patients diagnosed with in situ breast cancer (OR 0.68, 95 % CI 0.46 0.99) as well as with stage II + breast cancer (OR 0.77, 95 % CI 0.63-0.94), and for patients with >=3 Elixhauser comorbidities (OR 0.43, 95 % CI 0.26-0.71). Adherence to follow-up declined over time. Knowledge of associated factors may assist in improving access to care for breast cancer survivors. PMID- 27393618 TI - Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion. AB - Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50 % of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple negative breast cancer cells. PMID- 27393620 TI - Perioperative biology in primary breast cancer: selective targeting of vasopressin type 2 receptor using desmopressin as a novel therapeutic approach. PMID- 27393621 TI - Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer. AB - We determined the prevalence and characteristics of BRCA1/2 germline mutations in a large cohort of Chinese women with breast cancer. A total of 5931 unselected Chinese women with breast cancer were enrolled in this study and underwent testing for BRCA1/2 mutations. Of these, 543 patients were familial breast cancer, 1033 were early-onset disease (<=40 years) without family history of breast cancer, and 4355 were sporadic breast cancer. In total, 232 patients (3.9 %) carried a BRCA1 or BRCA2 mutation (110 in BRCA1and 122 in BRCA2) in this cohort of 5931 patients. BRCA1/2 mutation rate was 16.9 % (92/543) in familial breast cancers, 5.2 % (54/1033) in early-onset breast cancers (<=40 years), and 2.0 % in sporadic breast cancers (>40 years), respectively. The BRCA1/2 mutation rate was 27.0 % in 111 familial breast cancers diagnosed at and before the age of 40. 41.4 % of mutations in this cohort were specific for Chinese population. Recurrent mutations accounted for 44.8 % of the entire mutations in 2382 cases that BRCA1 and BRCA2 genes were fully sequenced in this study. Both BRCA1 and BRCA2 mutation carriers were significantly more likely to be early-onset and bilateral breast cancers, high-grade cancer, and to have a family history of breast cancer compared with non-carriers. BRCA1 mutation carriers were more likely to be triple-negative cancer than BRCA2 mutation carriers and non carriers. Our data provide guidelines for Chinese women with breast cancer who should undergo BRCA1/2 genetic testing; additionally, recurrent mutations account for nearly half of the mutations and some of them are specific for Chinese women. PMID- 27393623 TI - A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women. AB - Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women. PMID- 27393622 TI - SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer. AB - SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event free survival (EFS), and toxicity were secondary endpoints. Analyses were intent to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3-4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer. PMID- 27393624 TI - Factors associated with late HIV diagnosis in North-East Scotland: a six-year retrospective study. AB - OBJECTIVES: Late HIV diagnosis is associated with increased morbidity and mortality, increased risk of transmission, impaired response to antiretroviral therapy and increased health care costs. The aim of this study was to determine the factors associated with late HIV diagnosis in Grampian, North-East Scotland. STUDY DESIGN: A population based retrospective database analysis. METHODS: All newly diagnosed HIV positive individuals in Grampian, North-East Scotland between 2009 and 2014 were included in the study. Participants were classified as having a late diagnosis if the CD4 cell count at presentation was less than 350 cells/mm3. Socio-economic and demographic factors were investigated in relation to outcome (late diagnosis) using Chi-squared and Mann-Whitney tests. RESULTS: CD4 cell count results were available for 111 (89.5%) of the 124 newly diagnosed individuals during the study period. The prevalence of late diagnosis was 53.2% (n = 59). Those infected via heterosexual mode of transmission had a 2.83 times higher odds of late diagnosis (OR 2.83 [95% CI: 1.10-7.32]) than men who have sex with men (MSM) and those with no previous HIV testing had a 5.46 increased odds of late diagnosis (OR 5.46 [95% CI: 1.89-15.81]) compared to those who had previously been tested. Missed opportunities for HIV diagnosis were identified in 16.3% (n = 15) of participants. CONCLUSION: Heterosexual individuals and those with no previous HIV testing were more likely to be diagnosed late. Targeted initiatives to increase perception of HIV risk and uptake of testing in these risk groups are recommended. PMID- 27393625 TI - Language and infant mortality in a large Canadian province. AB - OBJECTIVES: Infant mortality in minority populations of Canada is poorly understood, despite evidence of ethnic inequality in other countries. We studied infant mortality in different linguistic groups of Quebec, and assessed how language and deprivation impacted rates over time. STUDY DESIGN: Population-level study of vital statistics data for 1,985,287 live births and 10,283 infant deaths reported in Quebec from 1989 through 2012. METHODS: We computed infant mortality rates for French, English, and foreign languages according to level of material deprivation. Using Kitagawa's method, we evaluated the impact of changes in mortality rates, and population distribution of language groups, on infant mortality in the province. RESULTS: Infant mortality declined from 6.05 to 4.61 per 1000 between 1989-1994 and 2007-2012. Most of the decline was driven by Francophones who contributed 1.39 fewer deaths per 1000 births over time, and Anglophones of wealthy and middle socio-economic status who contributed 0.13 fewer deaths per 1000 births. The foreign language population and poor Anglophones contributed more births over time, including 0.08 and 0.02 more deaths per 1000 births, respectively. Mortality decreased for Francophones and Anglophones in each level of deprivation. Rates were lower for foreign languages, but increased over time, especially for the poor. CONCLUSIONS: Infant mortality rates decreased for Francophones and Anglophones in Quebec, but increased for foreign languages. Poor Anglophones and individuals of foreign languages contributed more births over time, and slowed the decrease in infant mortality. Language may be useful for identifying inequality in infant mortality in multicultural nations. PMID- 27393626 TI - Accurate determination of rates from non-uniformly sampled relaxation data. AB - The application of non-uniform sampling (NUS) to relaxation experiments traditionally used to characterize the fast internal motion of proteins is quantitatively examined. Experimentally acquired Poisson-gap sampled data reconstructed with iterative soft thresholding are compared to regular sequentially sampled (RSS) data. Using ubiquitin as a model system, it is shown that 25 % sampling is sufficient for the determination of quantitatively accurate relaxation rates. When the sampling density is fixed at 25 %, the accuracy of rates is shown to increase sharply with the total number of sampled points until eventually converging near the inherent reproducibility of the experiment. Perhaps contrary to some expectations, it is found that accurate peak height reconstruction is not required for the determination of accurate rates. Instead, inaccuracies in rates arise from inconsistencies in reconstruction across the relaxation series that primarily manifest as a non-linearity in the recovered peak height. This indicates that the performance of an NUS relaxation experiment cannot be predicted from comparison of peak heights using a single RSS reference spectrum. The generality of these findings was assessed using three alternative reconstruction algorithms, eight different relaxation measurements, and three additional proteins that exhibit varying degrees of spectral complexity. From these data, it is revealed that non-linearity in peak height reconstruction across the relaxation series is strongly correlated with errors in NUS-derived relaxation rates. Importantly, it is shown that this correlation can be exploited to reliably predict the performance of an NUS-relaxation experiment by using three or more RSS reference planes from the relaxation series. The RSS reference time points can also serve to provide estimates of the uncertainty of the sampled intensity, which for a typical relaxation times series incurs no penalty in total acquisition time. PMID- 27393627 TI - Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma. AB - INTRODUCTION: Irreversible electroporation (IRE) utilizes short, high-voltage pulses to irreversibly permeabilize the cell membrane, resulting in apoptotic cell death. In addition to the irreversible zone, IRE creates a reversible zone that could be utilized for enhanced drug delivery. The hypothesis of this study is that a zone of reversible electroporation exists and allows for increased chemotherapy delivery. METHODS: Ten immunocompromised mice with orthotopic human pancreatic adenocarcinoma tumors (Panc1) were treated with either IRE between two doses of gemcitabine (15 mg/kg) (ECT) (N = 5) or gemcitabine alone (N = 5). Gemcitabine levels in the serum, liver, and pancreas were analyzed with liquid chromatography/mass spectrometry (LC/MS). RESULTS: Concentration of gemcitabine within reversibly electroporated pancreatic tissue was higher in mice receiving ECT compared to those receiving gemcitabine alone (13,567 ng/ml vs.4,126 ng/ml; P = 0.0009). Pancreatic gemcitabine levels were 5.52 and 5.96 times higher than liver and serum levels, respectively, in the ECT group compared to 2.85 and 2.53 times higher (P = 0.117, P = 0.058), respectively, in mice receiving gemcitabine alone. CONCLUSION: IRE can potentially reduce local recurrence by allowing increased drug delivery to the tissue in the reversible electroporation zone. This holds significant potential in augmenting efficacy of gemcitabine in treatment of locally advanced and borderline resectable pancreatic adenocarcinoma. J. Surg. Oncol. 2016;114:181-186. (c) 2016 Wiley Periodicals, Inc. PMID- 27393628 TI - Chain-length-dependent impact of band broadening on the molar-mass determination of synthetic polymers via size-exclusion chromatography. AB - The impact of band-broadening (BB) on the molar-mass determination of synthetic polymers via size-exclusion chromatography (SEC) is systematically studied. BB is simulated using the exponentially modified Gaussian (EMG) model, which combines the two inherent and distinct characteristics contributing to BB in SEC: symmetric Gaussian broadening and asymmetric skewing. It is demonstrated that BB both during the measurement of the analyte itself and during the calibration process has an individual impact on molar-mass determination. In this context, particularly skewing leads to a chain-length-dependent underestimation of molar masses, with deviations of the apparent from the true ones of only a few percent for low molar masses to up to 20% for high ones for reasonable extents of BB. The impact is shown to be independent of the shape of the analyte?s molar-mass distribution (MMD) and affects broad and multimodal MMDs similarly to narrow and unimodal ones. As a consequence, strategies are presented for a comprehensive quantitative correction of the observed effects, which may find their application in refined SEC software packages. The potential impact of the findings on general conceptions of repeatability and reproducibility within SEC experiments is discussed. PMID- 27393629 TI - Thioether bridged cationic cyclodextrin stationary phases: Effect of spacer length, selector concentration and rim functionalities on the enantioseparation. AB - The preparation and evaluation of four single thioether bridged cationic cyclodextrin (CD) chiral stationary phases (CSPs) with different spacer length, selector concentration and rim functionalities are reported. Mono-6-(1 vinyl/allyl/butenylimidazolium)-beta-CDs chloride were synthesized and clicked onto thiol silica to form three novel cationic native-CD-CSPs (CSP1, CSP2 and CSP3) and a post-synthetic phenylcarbamoylation of CSP2 was performed affording CSP4. The enantioseparation ability of the as-prepared CSPs were evaluated in high performance liquid chromatography (HPLC) by separating over forty enantiomers including isoxazolines, dansyl amino acids, flavonoids, troger's base, 4-chromanol, bendroflumethiazide and styrene oxide. Most of the enantiomers were well resolved with the resolution (Rs) of 4NPh-OPr reaching 12.68. The effects of spacer length, selector concentration and rim functionalities on the enantioseparation were investigated. A comparison of the current CSP with a commercial column (Cyclobond I 2000) was also conducted to reveal the superiors enantioselectivity of the as-prepared CSPs. PMID- 27393630 TI - Performance evaluation of tile-based Fisher Ratio analysis using a benchmark yeast metabolome dataset. AB - Performance of tile-based Fisher Ratio (F-ratio) data analysis, recently developed for discovery-based studies using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC*GC-TOFMS), is evaluated with a metabolomics dataset that had been previously analyzed in great detail, but while taking a brute force approach. The previously analyzed data (referred to herein as the benchmark dataset) were intracellular extracts from Saccharomyces cerevisiae (yeast), either metabolizing glucose (repressed) or ethanol (derepressed), which define the two classes in the discovery-based analysis to find metabolites that are statistically different in concentration between the two classes. Beneficially, this previously analyzed dataset provides a concrete means to validate the tile-based F-ratio software. Herein, we demonstrate and validate the significant benefits of applying tile-based F-ratio analysis. The yeast metabolomics data are analyzed more rapidly in about one week versus one year for the prior studies with this dataset. Furthermore, a null distribution analysis is implemented to statistically determine an adequate F ratio threshold, whereby the variables with F-ratio values below the threshold can be ignored as not class distinguishing, which provides the analyst with confidence when analyzing the hit table. Forty-six of the fifty-four benchmarked changing metabolites were discovered by the new methodology while consistently excluding all but one of the benchmarked nineteen false positive metabolites previously identified. PMID- 27393631 TI - [Not Available]. PMID- 27393632 TI - [Not Available]. AB - AIMS: To investigate the characteristics of adverse drug events (ADE) causing emergency medical admissions in the elderly. METHODS: Data were obtained from two prospective cross sectional studies with similar experimental design which were carried out in seven French emergency departments in 1999 and 2003. The proportion of ADE leading to admission, their severity and preventability were assessed in patients aged >=70 (group A) and compared to those of patients <70years (group B). RESULTS: Out of a total of 2907 patients, 1158 (39.8%) were >=70years of age. Among these, 17.1% were admitted as a result of an ADE vs. 13.2% in group B (p=0.004). ADE appeared to be more severe in group A than in group B. The part of preventable ADE did not significantly differ between the two groups (48.9% vs. 43.7%, respectively). CONCLUSION: ADE are a common preventable cause of unplanned admissions, especially in the elderly. PMID- 27393633 TI - Quality of life and costs of spasticity treatment in German stroke patients. AB - OBJECTIVE: To gather data about the medical and non-medical health service in patients suffering from post-stroke spasticity of the upper limb and evaluate treatment effectiveness and tolerability as well as costs over the treatment period of one year. METHODS: Prospective, non-interventional, multicenter, parallel-group study comparing effectivenessand costs of incobotulinumtoxinA (INCO) treatment (n = 118) to conventional (CON) antispastic therapy (n = 110) for upper limb spasticity after stroke in 47 clinical practices across Germany over a 1-year treatment period. IncobotulinumtoxinA was applied according to the individual treatment algorithms of each participating site and additional antispastic treatments were allowed. Primary efficacy objective was the reduction of the muscle tone measured by Ashworth scale. Responder analyses and logistic regressions were performed. Quality of life, measured by SF-12 questionnaire and functional disability were assessed. Besides calculating treatment costs, a cost utility analysis was performed. RESULTS: Responder rates of all muscle groups of the upper extremities were significantly higher in the treatment group (62.9-86.2 % vs. 15.5-26.9 %, p < 0.01). Total health service costs were twice as high in the INCO group, however cost-utility ratios were consistently superior compared to the control group. Lowest incremental costs were documented to improve the "physical health" dimension in quality of life. CONCLUSION: Higher responder rates, higher increases in quality of life and superior cost-utility ratios in the BoNT/A-treatment group underline guideline recommendations for botulinum toxin A treatment in focal or segmental spasticity. Results may partially be influenced by different patient demographics or disease severity at study entry. PMID- 27393634 TI - [Not Available]. AB - PURPOSE: The modalities for anti-dementia drugs' discontinuation are not consensual. OBJECTIVE: The objectives of the study were the followings, describe: i) the reasons for discontinuation of anti-dementia drugs of patients treated in a residency for dependent elderly people, ii) security of sudden discontinuation, iii) evolution of troubles. METHODS: Our longitudinal descriptive pilot study aimed at observing consequences of the sudden discontinuation of anti-dementia drugs in a population with a moderate to severe stage of Alzheimer's disease. The study took place in a French residency for dependent elderly people, treated with at least one of the following treatments: rivastigmine, donepezil, galantamine and/or memantine. Based on multidisciplinary decision, as recommended, patient's anti-dementia treatment have been stopped or not. Criteria have been collected for 6months and compared between the two groups: safety, motivation for discontinuation, score mini-mental state examination (MMSE), psycho-behavior criteria and finally the concomitant prescription of psychotropic drugs. RESULTS: Thirty-three patients were included: the revaluation of anti-dementia treatment led to 22 discontinuations and 11 continuations. Motivations to stop antidementia treatment were: too advanced dementia (48%), lack of therapeutic benefit (28%) or too much of psychotropic medications (24%). The sudden discontinuation was well tolerated with no withdrawal syndrome observed. The variation of MMSE at 6months was -1.8 (SD 2.2) in the discontinuation group (n=14) versus -2.2 (SD 2.0) in the continuation group (n=6). The psycho-behavior disorders have not been aggravated. A reduction in number of psychotropic drugs in the discontinuation group was observed. CONCLUSION: In this pilot study, the revaluation in accordance with the recommendations of the Haute autorite de sante (HAS) led to the discontinuation of two third of anti-dementia drugs. Safety of sudden discontinuation of MSD remains to be studied. PMID- 27393635 TI - [Not Available]. AB - The active patient participation in clinical trials is key for a competitive clinical research. Given this, the Health Industry Physicians and Actors Association (AMIPS) has set up a working group to make communication recommendations towards patients. The group was made of patients, investigators and industry sponsors representatives. Efficacious communication is rarely obtained because it is not clear what is possible to do ethically and regulatory and because of technical and financial constraints. After having identified the expectations and limitations for every actor category, the group has summarized all types of communication, in a sort of tool box, before and during the whole of a study. The benefits and regulatory prerequisites such as the submission to the Ethical Committee and to the National Data Information and Freedom Commission (CNIL) as well as the practical feasibility are described for each tool. PMID- 27393636 TI - [Not Available]. AB - OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated in pregnancy because of the many foetalmaternal complications they can induce. Yet, NSAIDs can be massively found in family medicine cabinets and they are over the counter drugs for most of them. Because of the actual trend of empowerment and public authorities encouraging self-medication, NSAIDs might be used. Our aim was to assess pregnant women's knowledge of NSAIDs. STUDY DESIGN: A descriptive study, through the distribution of 330 questionnaires to all pregnant women consulting at the Teaching hospital of Saint-Etienne, during a week, from February 11(th), 2014 to 19(th), 2014. RESULTS: The answering rate was 96.4%. Around 46% of pregnant women declared self-medicating. More than 1 in 3 women considered NSAIDs without danger starting from their 6th month of pregnancy. Eighty-six percent of women recognized ibuprofen as belonging to NSAISs. However, 1 in 2 women didn't consider Rhinadvil(r) (ibuprofene/pseudoephedrine) as such and approximately 40% for Aspegic(r) (lysine acetylsalicylate) and Aspirin(r) (acetylsalicylic acid). Danger's perception varied according to the galenic and the trade name: 60% of them thought that Rhinadvil(r) was without risks and around 1 in 2 women thought the same for Aspirin(r) and Aspegic(r). Eighty-six per cent of women recognized ibuprofen as belonging to NSAIDs. However, 1 in 2 women didn't consider Rhinadvil(r) as such and approximately 40% for Apegic(r) and Aspirin(r). CONCLUSION: Pregnant women's knowledge of NSAIDs is not satisfactory. They are not aware of their danger and do not know how to recognize them. Yet, self-medication is rising and its accessibility is made easier. A work on prevention and information is therefore essential. PMID- 27393637 TI - Physicochemical and bioactive properties of innovative resin-based materials containing functional halloysite-nanotubes fillers. AB - OBJECTIVE: This study aimed to assess the degree of conversion, microhardness, solvent degradation, contact angle, surface free energy and bioactivity (e.g., mineral precipitation) of experimental resin-based materials containing, pure or triclosan-encapsulated, aluminosilicate-(halloysite) nanotubes. METHODS: An experimental resin blend was prepared using bis-GMA/TEGDMA, 75/25wt% (control). Halloysite nanotubes (HNT) doped with or without triclosan (TCN) were first analyzed using transmission electron microscopy (TEM). HNT or HNT/TCN fillers were incorporated into the resin blend at different concentrations (5, 10, and 20wt%). Seven experimental resins were created and the degree of conversion, microhardness, solvent degradation and contact angle were assessed. Bioactive mineral precipitation induced by the experimental resins was evaluated through Raman spectroscopy and SEM-EDX. RESULTS: TEM showed a clear presence of TCN particles inside the tubular lumen and along the outer surfaces of the halloysite nanotubes. The degree of conversion, surface free energy, microhardness, and mineral deposition of polymers increased with higher amount of HNTs. Conversely, the higher the amount (20wt%) of TCN-loaded HNTs the lower the microhardness of the experimental resins. SIGNIFICANCE: The incorporation of pure or TCN-loaded aluminosilicate-(halloysite) nanotubes into resin-based materials increase the bioactivity of such experimental restorative materials and promotes mineral deposition. Therefore, innovative resin-based materials containing functional halloysite-nanotube fillers may represent a valuable alternative for therapeutic minimally invasive treatments. PMID- 27393638 TI - Girl Talk: A Smartphone Application to Teach Sexual Health Education to Adolescent Girls. AB - STUDY OBJECTIVE: Produce Girl Talk, a free smartphone application containing comprehensive sexual health information, and determine the application's desirability and appeal among teenage girls. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Thirty-nine girls ages 12 to 17 years from Rhode Island participated in a 2-phase prospective study. In phase I, 22 girls assessed a sexual health questionnaire in focus groups. In phase II, 17 girls with iPhones used Girl Talk for 2 weeks and answered the revised sexual health questionnaire and interview questions before and after use. MAIN OUTCOME MEASURES: Participants' responses to the sexual health questionnaire, interviews, and time viewing the application were used to determine feasibility and desirability of Girl Talk. RESULTS: Girl Talk was used on average for 48 minutes during participants' free time on weekends for 10- to 15-minute intervals. Reported usefulness of Girl Talk as a sexual health application from baseline (6 participants) to follow-up (16 participants) increased significantly (35.3% vs 94.1%; P < .001). Knowledge improved most in topics related to anatomy and physiology (70.5% to 74.7% out of 7 questions), sexuality and relationships (76.5% to 80.0% out of 10 questions), and STI prevention (75.6% to 79.0% out of 7 questions). Most phase II participants (13 out of 17, or 76.5%) were exposed to sexual health education before using Girl Talk, but 16 out of 17 participants (94.1%) stated that the application provided new and/or more detailed information than health classes. CONCLUSION: Girl Talk can potentially connect teenage girls to more information about sexual health vs traditional methods, and participants recommended the application as a valuable resource to learn about comprehensive sexual health. PMID- 27393639 TI - Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic steatohepatitis. AB - Nonalcoholic steatohepatitis (NASH) is considered to be a common health problem since the incidence of nonalcoholic fatty liver disease (NAFLD) has increased in recent years. Disturbed hepatic cholesterol homeostasis and free cholesterol accumulation in liver results in increased oxidative stress leading to the endoplasmic reticulum (ER) stress. Activated ER stress maintains protein homeostasis however, delayed or inadequate ER stress responses may induce fat accumulation, insulin resistance, inflammation, apoptosis, and autophagy, all of which increase with age and play crucial roles in the pathogenesis of NASH. In aging research, there is a growing interest for the role of ER stress in the progression of NASH since aging seems to favor NAFLD according to its pathogenesis. On the other hand, specific microRNAs (miRNAs) expression profiles are strongly related with ER stress as well as NASH progresses. This review highlights molecular mechanisms related to ER stress in the pathogenesis of NASH and miRNAs for the progression and treatment of the disease. PMID- 27393641 TI - Small Bowell Malignant Melanoma-Report of Three Cases and Review of Literature. AB - Malignant melanomas have a predilection to metastasize to the small bowel. Three patients with malignant melanoma involving the small bowel are reported. Two patients were operated on for small bowel obstruction and the third for gastrointestinal bleeding with anemia. Two patients remained well 6 month and 2 years, respectively, after surgery. One patient died of metastatic cerebral melanoma 6 months postoperatively. One should suspect small bowel metastasis in every patient with malignant melanoma in his past medical history, who presents with recent changes in bowel habits, intestinal obstruction or gastrointestinal bleeding. Preoperative assessment can only raise the suspicion, even with advanced imaging methods: capsule endoscopy, enteroscopy, CT or PET-CT. The only therapeutic procedure is surgical resection, offering both short term survival as well as an improvement in the quality of life. Although prognosis is dismal there are factors associated with prolonged survival: complete surgical resection with no residual primary or metastatic tumor, so-called primary small bowel tumors in patients aged more then 60 years, LDH < 200 U/L, lack of tumor spread in mesenteric lymph nodes. PMID- 27393640 TI - Integrative analyses unveil speciation linked to host plant shift in Spialia butterflies. AB - Discovering cryptic species in well-studied areas and taxonomic groups can have profound implications in understanding eco-evolutionary processes and in nature conservation because such groups often involve research models and act as flagship taxa for nature management. In this study, we use an array of techniques to study the butterflies in the Spialia sertorius species group (Lepidoptera, Hesperiidae). The integration of genetic, chemical, cytogenetic, morphological, ecological and microbiological data indicates that the sertorius species complex includes at least five species that differentiated during the last three million years. As a result, we propose the restitution of the species status for two taxa often treated as subspecies, Spialia ali (Oberthur, 1881) stat. rest. and Spialia therapne (Rambur, 1832) stat. rest., and describe a new cryptic species Spialia rosae Hernandez-Roldan, Dapporto, Dinca, Vicente & Vila sp. nov. Spialia sertorius (Hoffmannsegg, 1804) and S. rosae are sympatric and synmorphic, but show constant differences in mitochondrial DNA, chemical profiles and ecology, suggesting that S. rosae represents a case of ecological speciation involving larval host plant and altitudinal shift, and apparently associated with Wolbachia infection. This study exemplifies how a multidisciplinary approach can reveal elusive cases of hidden diversity. PMID- 27393642 TI - The role of coacervation and phase transitions in the sandcastle worm adhesive system. AB - Sandcastle worms, Phragmatopoma californica (Fewkes), live along the western coast of North America. Individual worms build tubular shells under seawater by gluing together sandgrains and biomineral particles with a multipart, rapid-set, self-initiating adhesive. The glue comprises distinct sets of condensed, oppositely charged polyelectrolytic components-polyphosphates, polysulfates, and polyamines-that are separately granulated and stored at high concentration in distinct cell types. The pre-organized adhesive modules are secreted separately and intact, but rapidly fuse with minimal mixing and expand into a crack penetrating complex fluid. Within 30s of secretion into seawater, the fluid adhesive transitions (sets) into a porous solid adhesive joint. The nano- and microporous structure of the foamy solid adhesive contributes to the strength and toughness of the adhesive joint through several mechanisms. A curing agent (catechol oxidase), co-packaged into both types of adhesive granules, covalently cross-links the adhesive and becomes a structural component of the final adhesive joint. The overall effectiveness of the granulated sandcastle glue is more a product of the cellular sorting and packaging mechanisms, the transition from fluid to solid following secretion, and its final biphasic porous structure as it is of its composition or any particular amino acid modification. PMID- 27393643 TI - Usability Testing of a National Substance Use Screening Tool Embedded in Electronic Health Records. AB - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is currently being implemented into health systems nationally via paper and electronic methods. OBJECTIVE: The purpose of this study was to evaluate the integration of an electronic SBIRT tool into an existing paper-based SBIRT clinical workflow in a patient-centered medical home. METHODS: Usability testing was conducted in an academic ambulatory clinic. Two rounds of usability testing were done with medical office assistants (MOAs) using a paper and electronic version of the SBIRT tool, with two and four participants, respectively. Qualitative and quantitative data was analyzed to determine the impact of both tools on clinical workflow. A second round of usability testing was done with the revised electronic version and compared with the first version. RESULTS: Personal workflow barriers cited in the first round of testing were that the electronic health record (EHR) tool was disruptive to patient's visits. In Round 2 of testing, MOAs reported favoring the electronic version due to improved layout and the inclusion of an alert system embedded in the EHR. For example, using the system usability scale (SUS), MOAs reported a grade "1" for the statement, "I would like to use this system frequently" during the first round of testing but a "5" during the second round of analysis. CONCLUSIONS: The importance of testing usability of various mediums of tools used in health care screening is highlighted by the findings of this study. In the first round of testing, the electronic tool was reported as less user friendly, being difficult to navigate, and time consuming. Many issues faced in the first generation of the tool were improved in the second generation after usability was evaluated. This study demonstrates how usability testing of an electronic SBRIT tool can help to identify challenges that can impact clinical workflow. However, a limitation of this study was the small sample size of MOAs that participated. The results may have been biased to Northwell Health workers' perceptions of the SBIRT tool and their specific clinical workflow. PMID- 27393644 TI - [Not Available]. AB - Itraconazole is a triazole antifungal agent that is active against Aspergillus, histoplasmosis, and rare fungal infections. Itraconazole exhibit marked variability in drug concentration as a result of inconsistent absorption, metabolism, or interaction with concomitant medications. Preclinical and clinical data have exhibited a relationship between serum concentrations and treatment efficacy or toxicity, thus therapeutic drug monitoring (TDM) of itraconazole is largely used to optimise therapy. The analysis of bibliographic data demonstrate that, even if the utility of itraconazole's TDM has not been proved by randomized controlled trial or pharmacoeconomics studies, it could be useful for managing an absence of response or a drug-drug interactions, or interpreting an adverse effect. However, the interest of this monitoring was proved only in some populations of patients (neutropenics or AIDS patients) so its level of proof varies between levels "potentially useful" and "recommended". PMID- 27393645 TI - [Not Available]. AB - Voriconazole is a major antifungal drug with activity against endemic fungi, Candida and Aspergillus species in immunocompromised patients. Voriconazole has a good bioavailability, an high protein binding percentage in plasma and is metabolized in liver via CYP2C19. It presents important neuro- and hepatotoxicities. Some studies determined trough concentrations of voriconazole in plasma using liquid chromatography coupled with UV or tandem mass detection. These studies showed a relationship between trough concentrations of voriconazole and efficacy or toxicity. Indeed, some studies reported a relationship between a lack of clinical response and concentrations below 1 or 2 MUg/mL according to the localization of infection, while toxicities are frequently observed at concentrations above 5 MUg/mL. Some particular populations will have to be taken into account such as children, patients with hemodialysis-dependant renal deficiency or hepatic insufficiency, cystic fibrosis patients or those treated concomitantly with interfering drugs. According to our survey, herapeutic drug monitoring of voriconazole appearsrecommended. However, controlled studies are still necessary to validate it prospectively and to evaluate pharmacokinetically based methods proposed for individual dose adjustment. PMID- 27393646 TI - [Not Available]. AB - Posaconazole, systemic antifungal marketed in France since 2006, is indicated as second line in curative treatment of invasive fungal infections (IFI) (aspergillosis. . . ) and prophylaxis of IFI in patients receiving chemotherapy or hematopoietic stem cell transplantation. The analysis of the literature indicates a concentration-efficacy relationship, but to date, no study has been able to show a concentration-toxicity correlation due to its favourable safety profile and the difficulty to obtain high concentrations. In curative, maintenance of trough plasma concentrations between 0.5 and 1.5 mg/L seems to be associate with an efficacy. In prophylaxis, a threshold of 0.5 mg/L corresponds to a minimal exposure. However this target is not yet well defined. Saturation of absorption above the 800 mg oral dose limits the adjustment of concentrations. As such, the Therapeutic Drug Monitoring of posaconazole can be recommended. PMID- 27393647 TI - [Not Available]. AB - Aripiprazole inaugurates a new generation of antipsychotics called dopamine serotonin system stabilizers. Its mechanism of action is different as aripiprazole is a partial dopamine D2 and serotonin 5-HT1A receptor agonist and 5 HT2A receptor antagonist. Therefore, aripiprazole is thought to have an antagonistic action in the mesolimbic pathway but an agonistic action in the mesocortical pathway, tending to normalize the dopaminergic transmission regardless of the type of imbalance. Clinical trials involving children and adolescents have demonstrated the efficacy of aripiprazole in bipolar disorders, schizophrenia, mood disorders associated with pervasive developmental disorders, in tics and Tourette's. The most frequent side effects are extrapyramidal symptoms and sleepiness and are dose-dependant. Nevertheless, contrary to other second-generation antipsychotics available in France, it induces little weight gain, does not modify lipid and glucidic profiles, does not increase prolactin levels, or induce QTc lengthening. The main advantage of aripiprazole is its good safety profile, with different toxicity targets to other secondgeneration antipsychotics available in France. Aripiprazole appears to be an alternative for children and adolescents who are vulnerable to these side effects and are having trouble coping with them. PMID- 27393648 TI - Identification of species based on DNA barcode using k-mer feature vector and Random forest classifier. AB - DNA barcoding is a molecular diagnostic method that allows automated and accurate identification of species based on a short and standardized fragment of DNA. To this end, an attempt has been made in this study to develop a computational approach for identifying the species by comparing its barcode with the barcode sequence of known species present in the reference library. Each barcode sequence was first mapped onto a numeric feature vector based on k-mer frequencies and then Random forest methodology was employed on the transformed dataset for species identification. The proposed approach outperformed similarity-based, tree based, diagnostic-based approaches and found comparable with existing supervised learning based approaches in terms of species identification success rate, while compared using real and simulated datasets. Based on the proposed approach, an online web interface SPIDBAR has also been developed and made freely available at http://cabgrid.res.in:8080/spidbar/ for species identification by the taxonomists. PMID- 27393649 TI - Genetic diversity and breeding history of Winter Mushroom (Flammulina velutipes) in China uncovered by genomic SSR markers. AB - Flammulina velutipes is one of the most widely cultivated mushroom species in China. However, its genetic background remains poorly understood due to the limited sampling and poor molecular markers used. In this study, 124 F. velutipes strains were employed, including 110 cultivars and 14 wild strains, and 25 new SSR markers were developed based on the genome of F. velutipes. A total of 153 alleles were detected in 124 strains to investigate the improper cultivar naming, genetic diversity and breeding history of F. velutipes in China. Our fingerprinting analyses indicated that 65 strains can be differentiated from the total of 124 strains, and over 53% of the strains are labeled with improper commercial names. The genetic diversities of wild strains are higher than those of the cultivars, suggesting that wild strains may harbor a large "arsenal" gene pool in nature available for strain breeding. The white cultivars in China were originally introduced from Japan, while the yellow cultivars were directly domesticated from wild strains isolated from southeastern China or hybridized between the white cultivars and yellow strains. PMID- 27393651 TI - The Arab genome: Health and wealth. AB - The 22 Arab nations have a unique genetic structure, which reflects both conserved and diverse gene pools due to the prevalent endogamous and consanguineous marriage culture and the long history of admixture among different ethnic subcultures descended from the Asian, European, and African continents. Human genome sequencing has enabled large-scale genomic studies of different populations and has become a powerful tool for studying disease predictions and diagnosis. Despite the importance of the Arab genome for better understanding the dynamics of the human genome, discovering rare genetic variations, and studying early human migration out of Africa, it is poorly represented in human genome databases, such as HapMap and the 1000 Genomes Project. In this review, I demonstrate the significance of sequencing the Arab genome and setting an Arab genome reference(s) for better understanding the molecular pathogenesis of genetic diseases, discovering novel/rare variants, and identifying a meaningful genotype-phenotype correlation for complex diseases. PMID- 27393650 TI - Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERbeta/MiR-95 and IGF-1R, PI3K/Akt signaling pathways. AB - Calycosin, the main component extractable from the herb Radix astragali, has been shown to inhibit cellular proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanisms by the way in which this occurs remain unclear. In the present study, we aimed to determine the potential effects of calycosin on proliferation in colorectal cancer cells in vitro and in vivo and to elucidate the underlying molecular mechanisms of action. Colorectal cancer cell lines SW480 and LoVo and cervical cancer cell line HeLa were treated with various concentrations of calycosin or plus ER beta (ERbeta) inhibitor PHTPP. The CCK8 assay, flow cytometry, and Hoechst 33258 stain were used to assess the effects on cellular proliferation and apoptosis. The mRNA levels of ERbeta and miR-95 were quantified by real-time PCR. The protein expression levels of ERbeta, ERalpha, IGF-1R, and p-Akt were evaluated by Western blot analysis. We demonstrated that calycosin inhibited the proliferation in SW480 and LoVo cells and induced apoptosis, particularly in SW480 cells, but not in HeLa cells. Calycosin increased ERbeta expression and reduced the ERalpha, IGF-1R, and p-Akt expression alongside down-regulation of miR-95 in SW480 cells. Inhibiting ERbeta blocked the change of miR-95 and the resulting increase in apoptosis in SW480 cells. Additionally, calycosin significantly suppressed xenograft tumor growth in nude mice. In conclusion, calycosin exerts an inhibitory effect on proliferation of CRC cells in vivo and in vitro, through ERbeta-mediated regulation of the IGF-1R, PI3K/Akt signaling pathways and of miR-95 expression. PMID- 27393652 TI - Genetic association of MYH genes with hereditary hearing loss in Korea. AB - BACKGROUND: Myosin is a key protein involved in regulating the shape and motility of cells. The MYH9 and MYH14 genes, which encode non-muscle myosin heavy chain IIA (NMMHC II-A) and IIC (NMMHC II-C), respectively, are expressed in the inner ear. These myosin genes are known to be associated with autosomal dominant non syndromic hearing loss (ADNSHL); however, genetic studies in patients with ADNSHL in Korea have rarely been reported. METHODS: We analyzed the MYH9 and MYH14 genes in 75 Korean patients with ADNSHL. RESULTS: We identified 4 possible pathogenic variants: a novel variant p.F1303L and 2 previously reported variants (p.R1730C and p.R1785C) in the MYH9 gene, and a novel variant p.A1868T in the MYH14 gene. All the variants were located in the myosin tail domain, which is essential for the interaction of myosin with actin. These variants were predicted to be possibly pathogenic by functional prediction tools and were absent in 100 unrelated normal controls. CONCLUSION: These results suggest that all the variants identified in this study have a strong potential to affect the structural stability and/or function of non-muscle myosin in the inner ear, which might lead to ADNSHL. This study establishes the link between the genotype and development of ADNSHL and contributes to the establishment of Korean database for hereditary hearing loss. PMID- 27393653 TI - Maternal and neonatal leptin and leptin receptor polymorphisms associated with preterm birth. AB - Leptin (LEP) and leptin receptor (LEPR) are suggested to play a role in female reproduction and especially in pregnancy Both LEP and LEPR are synthesized by the pregnant female and embryo. The link between genetic polymorphisms of LEP and LEPR and preterm birth (PTB) is unknown. We studied maternal and neonatal LEP and LEPR genetic polymorphisms and the association with PTB. Blood for DNA analysis was collected from Israeli mothers and from venous umbilical of their respected idiopathic preterm newborns (24-36weeks, n=102) and control term newborns (>37weeks, n=158). Genotypes of maternal and neonatal LEP (rs7799039) and LEPR (rs1137101) polymorphisms were analyzed by restriction fragment length polymorphism analysis. Genotype-phenotype association was assayed using SPSS program. We found a significant independent increased risk of PTB for women and neonates bearing the homozygous AA form of LEP genotype; where women carrying AA LEP genotype had 2.53 fold ([CI] 1.367-4.685, p=0.03) and 2.38 fold ([CI] 1.150 4.915, p=0.019) increased risk for PTB compared to AG and GG genotypes, respectively. Neonates carrying the LEP AA genotype had a significant 2.8 fold increased risk for PTB compared to the AG genotype (CI11.040-7.577, p=0.042). Maternal LEPR polymorphism was significantly associated with severe PTB; where women carrying the AA and AG genotypes had a significant 4.32 and 4.76 fold increased risk for severe PTB compared to women carrying the GG genotype (CI=1.090-17.112 and 1.332-17.027, respectively p=0.035). IN CONCLUSION: maternal and neonatal LEP and LEPR polymorphisms are significantly associated with increased risk for PTB. PMID- 27393654 TI - In situ growth of a C-terminal interferon-alpha conjugate of a phospholipid polymer that outperforms PEGASYS in cancer therapy. AB - Conjugating therapeutic proteins and peptides to poly(ethylene glycol) (PEG) can improve their pharmacokinetics and therapeutic potential. However, PEGylation suffers from non-specific conjugation, low yield and immunogenicity. Herein we report a new and general methodology to synthesize a protein-polymer conjugate with site-specificity, high yield and activity, long circulation half-life and excellent therapeutic efficacy. A phospholipid polymer, poly(2 methacryloyloxyethyl phosphorylcholine) (PMPC), was grown solely from the C terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) PMPC conjugate of interferon-alpha in high yield. Notably, the PMPC conjugate showed 194- and 158-fold increases in systemic exposure and tumor uptake as compared with interferon-alpha, respectively. The in vitro antiproliferative bioactivity of the PMPC conjugate was 8.7-fold higher than that of PEGylated interferon-alpha (PEGASYS). In a murine cancer model, the PMPC conjugate completely inhibited tumor growth and cured 75% mice, whereas at the same dose, no mice treated with interferon-alpha or PEGASYS survived. We believe that this new approach to synthesize C-terminal protein conjugates of PMPC may be applicable to a large subset of protein and peptide drugs, thereby providing a general platform for the development of next-generation protein therapeutics. PMID- 27393655 TI - Integrin-binding elastin-like polypeptide as an in situ gelling delivery matrix enhances the therapeutic efficacy of adipose stem cells in healing full-thickness cutaneous wounds. AB - One crucial issue in stem cell therapy used for tissue repair is often the lack of selective carriers to deliver stem cells to the site of injury where the native extracellular matrix is pathologically damaged or lost. Therefore, it is necessary to develop a biomaterial that is permissive to stem cells and is suitable to replace injured or missing matrix. The major aim of this study is to investigate the potential of an RGD-containing elastin-like polypeptide (REP) with the structure TGPG[VGRGD(VGVPG)6]20WPC to engraft adipose stem cells (ASC) to full-thickness excisional wounds in mice. We implanted REP into the wound defects via body temperature-induced in situ aggregation. Engrafted REP exhibited a half-life of 2.6days in the wounds and did not elicit any pathological immune responses. REP itself significantly accelerated wound closure and reepithelialization and upregulated the expression of dermal tissue components. A combined administration of REP and ASC formed a hydrogel-like ASC/REP composite, which provided better neovascularization than the use of ASCs alone and increased the viability of transplanted ASC, improving overall wound healing. In vitro and in vivo mechanistic investigations suggested that REP enhances ASC survival at least in part via the Fak/Src adhesion-induced upregulation of Mek/Erk and PI3K/Akt survival pathways. We conclude that REP is a promising therapeutic agent for the improvement of stem cell-based therapy for enhanced tissue regeneration and repair. PMID- 27393656 TI - A method for amplification of unknown flanking sequences based on touchdown PCR and suppression-PCR. AB - Thermal asymmetric staggered PCR is the most widely used technique to obtain the flanking sequences. However, it has some limitations, including a low rate of positivity, and complex operation. In this study, a improved method of it was made based on suppression-PCR and touchdown PCR. The PCR fragment obtained by the amplification was used directly for sequencing after gel purification. Using this improved method, the positive rate of amplified flanking sequences of the ATMT mutants reached 99%. In addition, the time from DNA extraction to flanking sequence analysis was shortened to 2 days with about 6 dollars each sample. PMID- 27393657 TI - [Not Available]. AB - Clinical Investigation Centres (CICs) are academic organisations for performing clinical studies. They are a part of a national network which is co-ordinated by French national institute for health and medical research (Inserm), and the head office of healthcare provision (DGOS). There are working groups and specialised networks within the overall CIC network. The Harmonisation of CIC Procedures (HPCIC) group wrote a manual of good professional practices for clinical research. This manual is described here. This manual was written by consensus. It was approved by the coordinators of all CICs, external experts, and validated by representatives of both Inserm and the General directorate of healthcare provision (DGOS). The CIC Good Professional Practices manual is a guide divided into two sections. The first section covers the general management of a CIC (common to all CICs). The second section covers the core activities of CICs, running clinical studies (clinical study coordination, clinical investigation, data management, statistical analysis, valorisation). This manual is available for all CICs and any other clinical research organisations. It will serve as a basis for CIC self-quality evaluation, audits between CICs, and external audits. This manual shows how much the CICs want to standardise practices and procedures nationwide to offer their partners the best quality in performing clinical studies. PMID- 27393658 TI - [Not Available]. AB - INTRODUCTION: We present here results of methotrexate, in term of efficacy and tolerance, administrated in 21 Tunisian patients with severe psoriasis. METHODS: It was a retrospective study conducted between january 2002 and december 2009 in the department of dermatology of Charles Nicolle Hospital of Tunis. We have included 21 patients with severe psoriasis treated by methotrexate. RESULTS: Patients were 53year-middle aged with a sex-ratio=6. Psoriasis evolved for a mean of 10years (1month-60years). Patients had: plaque psoriasis (n=18, 85.8%) with 63% body surface involvement, erythrodermic psoriasis (n=2, 9.5%) and psoriatic arthritis (n=1, 4.7%). Methotrexate was orally administrated at an initial dose of 5-7.5mg/week. The maximum dose was of 7.5mg-12.5mg/week. Complete remission was achieved in 62% of cases and partial remission in 28.5% of cases. Haematological and hepatic toxicities were observed in 2 patients (9.5%). Mean remission period was of 14months (3months-3years). Seven patients had severe relapses. CONCLUSION: Our study concluded to the efficacy of methotrexate in severe psoriasis with a high rate and long term remission, despite lower doses than those classically used in the literature. PMID- 27393659 TI - Functional evolution of the OAS1 viral sensor: Insights from old world primates. AB - Infections with viral pathogens impose considerable selective pressure on host defensive genes. Those genes at the forefront, responsible for identifying and binding exogenous molecular viral components, will carry the hallmarks of this struggle. Oligoadenylate synthetase (OAS) enzymes play a major role in the innate defense against a large number of viruses by acting as sensors of viral infections. Following their up-regulation by the interferon pathway, OASs bind viral dsRNA and then signal ribonuclease L (RNase L) to degrade RNA, shutting down viral and host protein synthesis. We have investigated the evolution of OAS1 in twenty-two Old World monkey species. We identified a total of 35 codons with the earmarks of positive selection and we performed a comprehensive analysis of their functional significance using in silico modeling of the OAS1 protein. Subdividing OAS1 into functional domains revealed intense purifying selection in the active domain but significant positive directional selection in the RNA binding domain (RBD), the region where OAS1 binds viral dsRNA. The modeling analysis revealed a concentration of rapidly evolving residues in one region of the RBD suggestive of the sub-functionalization of different regions of the RBD. This analysis also identified several positively selected residues circumscribing the entry to the active site suggesting adaptive evasion of viral antagonism and/or selection for production of oligoadenylate of different length. PMID- 27393660 TI - Imported and autochthonous leprosy presenting in Madrid (1989-2015): A case series and review of the literature. AB - BACKGROUND: Leprosy remains infrequent in non-endemic areas. The objective of this study was to describe the cases of leprosy reviewed at a referral unit for imported diseases in Europe and to compare these findings with published data on imported leprosy. METHODS: Cases of leprosy evaluated at a referral centre are described and salient features of autochthonous and imported cases are compared. A review of the literature on imported leprosy was performed. RESULTS: During the study period, 25 patients with leprosy were followed-up (10 were autochthonous cases and 15 were considered to be imported). Regarding imported cases, the majority were diagnosed in Latin American immigrants (10/15, 67%), mean age was 42 years, there were no differences in gender distribution, estimated average time from arrival in Spain to first visit at the unit was 3 years and from symptom onset to diagnosis was 2 years. Over 80% of imported cases had multibacillary disease and over one third of patients had been previously diagnosed with leprosy. One third had received alternate incorrect diagnoses initially, <50% of patients with imported leprosy completed standard therapy and were considered cured and over one third were lost to follow-up. CONCLUSIONS: Leprosy remains a complex disease for healthcare professionals unfamiliar with this infection. Manifestations are polymorphic so misdiagnoses and consequent delays in diagnosis are not infrequent and may lead to resulting disabilities. Early diagnosis and management are essential to prevent sequelae and possible transmission. Improving access to health care, especially for vulnerable groups, would be necessary to advance in the control of this disease. PMID- 27393661 TI - Genes coding for cyclin-dependent kinase inhibitors are fragile in Xenopus. AB - Cell proliferation is strictly regulated by the dosage balance among cell-cycle regulators such as CDK/cyclin complexes and CDK-Inhibitors. Even in the allotetraploid genome of Xenopus laevis, the dosage balance must be maintained for animals to stay alive, and the duplicated homeologous genes seem to have gradually changed, through evolution, resulting in the best genes for them to thrive. In the Xenopus laevis genome, while homeologous gene pairs of CDKs are fundamentally maintained and a few cyclin genes are amplified, homeologous gene pairs of the important CDK-Inhibitors, CDKn1c and CDKn2a, are deleted from chromosomes L and S. Although losses of CDKn1c and CDKn2a can lead to diseases in humans, their loss in X. laevis does not affect the animals' health. Also, another gene coding CDKn1b is lost besides CDKn1c and CDKn2a in the genome of Xenopus tropicalis. These findings suggest a high resistance of Xenopus to diseases. We also found that CDKn2c.S expression is higher than that of CDKn2c.L, and a conserved noncoding sequence (CNS) of CDKn2c genomic loci on X. laevis chromosome S and X. tropicalis has an enhancement activity in regulating the different expression. These findings together indicate a surprising fragility of CDK inhibitor gene loci in the Xenopus genome in spite of their importance, and may suggest that factors other than CDK-inhibitors decelerate cell-cycling in Xenopus. PMID- 27393662 TI - CT imaging-based determination and classification of anatomic variations of left gastric vein. AB - BACKGROUND: Precise determination and classification of left gastric vein (LGV) anatomy are helpful in planning for gastric surgery, in particular, for resection of gastric cancer. However, the anatomy of LGV is highly variable. A systematic classification of its variations is still to be proposed. We aimed to investigate the anatomical variations in LGV using CT imaging and develop a new nomenclature system. METHOD: We reviewed CT images and tracked the course of LGV in 825 adults. The frequencies of common and variable LGV anatomical courses were recorded. Anatomic variations of LGV were proposed and classified into different types mainly based on its courses. The inflow sites of LGV into the portal system were also considered if common hepatic artery (CHA) or splenic artery (SA) could not be used as a frame of reference due to variations. RESULTS: Detailed anatomy and courses of LGV were depicted on CT images. Using CHA and SA as the frames of reference, the routes of LGV were divided into six types (i.e., PreS, RetroS, Mid, PreCH, RetroCH, and Supra). The inflow sites were classified into four types (i.e., PV, SV, PSV, and LPV). The new classification was mainly based on the courses of LGV, which was validated with MDCT in the 805 cases with an identifiable LGV, namely type I, RetroCH, 49.8 % (401/805); type II, PreS, 20.6 % (166/805); type III, Mid, 20.0 % (161/805); type IV, RetroS, 7.3 % (59/805); type V, Supra, 1.5 % (12/805); and type VI, PreCH, 0.7 % (6/805). Type VII, designated to the cases in which SA and CHA could not be used as frames of reference, was not observed in this series. CONCLUSIONS: Detailed depiction of the anatomy and courses of LGV on CT images allowed us to evaluate and develop a new classification and nomenclature system for the anatomical variations of LGV. PMID- 27393663 TI - Are human iNKT cells keeping tabs on lipidome perturbations triggered by oxidative stress in the blood? AB - The central paradigm of conventional MHC-restricted T cells is that they respond specifically to foreign peptides, while displaying tolerance to self-antigens. In contrast, it is now becoming clear that a number of innate-like T cell subsets CD1-restricted T cells, Vgamma9Vdelta2 T cells, and MAIT cells-may operate by different rules: rather than focusing on the recognition of specific foreign antigens, these T cells all appear to respond to alterations to lipid-related pathways. By monitoring perturbations to the "lipidome," these T cells may be able to spring into action to deal with physiological situations that are of self as well as microbial origin. iNKT cells are a prime example of this type of lipidome-reactive T cell. As a result of their activation by self lyso phospholipid species that are generated downstream of blood lipid oxidation, human iNKT cells in the vasculature may respond sensitively to a variety of oxidative stresses. Some of the cytokines produced by activated iNKT cells have angiogenic effects (e.g., GM-CSF, IL-8), whereas others (e.g., IFN-gamma) are pro inflammatory factors that can propagate vascular pathology by influencing the functions of macrophages and dendritic cells. Consistent with this, evidence is accumulating that iNKT cells contribute to atherosclerosis, which is one of the most common inflammatory pathologies, and one that is integrally related to characteristics of the lipidome. PMID- 27393664 TI - MAIT, MR1, microbes and riboflavin: a paradigm for the co-evolution of invariant TCRs and restricting MHCI-like molecules? AB - MAIT cells express an invariant TCR that recognizes non-peptidic microbial antigens presented by the non-polymorphic MHCI-like molecule, MR1. We briefly describe how the antigens recognized by MAIT cells are generated from an unstable precursor of the riboflavin (Vitamin B2) biosynthesis pathway, as well as the main features of MAIT cells in comparison with other related T cell subsets. In silico analysis of bacterial genomes shows that the riboflavin biosynthesis pathway is highly prevalent in all groups of Prokaryotes with, however, notable exceptions. We discuss the putative functions and the evolution of the MAIT/MR1 couple: it appeared in the ancestors of mammals and is highly conserved across this group, but was independently lost in three orders. We describe the four instances of known invariant TCR and MHC-I-like molecules encountered in Vertebrates. Both T cells bearing semi-invariant TCR and the associated, evolutionarily conserved MHC-I related molecules have been found in mammals or in amphibians, which suggests that other MHC1-like/invariant TCR couples might be present in other classes of Vertebrates to detect generic microbial compounds. This allows us to discuss how the recognition of riboflavin precursor derivatives by the MAIT TCR may be a way to detect invasive microbes in specific organs, and may epitomize other invariant T cell systems across vertebrates. PMID- 27393667 TI - Keynote symposia. PMID- 27393666 TI - The effect of synthetic ceramide analogues on gastritis and esophagitis in rats. AB - The effects of ceremide analogues on esophagitis and gastritis in rats were examined. Gastritis induced by indomethacin was significantly reduced after CY3325 and CY3723 treatment, whereas other analogues had no effect. The amount of malondialdehyde in gastritis was significantly reduced by CY3325 or CY 3723. CY3325 or CY 3723 decreased the glutathione levels in gastritis. The myeloperoxidase level in gastritis is increased, and its increment was decreased by CY3325 and CY3723. In reflux esophagitis, the ulceration was decreased by CY3325, CY3723. The gastric volume and acid output are reduced, whereas the pH value is increased by CY3325 or CY3723 after esophagitis. These results suggest that ceramide analogues, CY3325 and CY3723, can prevent the development of gastritis and reflux esophagitis in rats. PMID- 27393668 TI - Plenary symposia. PMID- 27393670 TI - Plant symposia. PMID- 27393669 TI - Animal symposia. PMID- 27393665 TI - Immunotherapeutic strategies targeting natural killer T cell responses in cancer. AB - Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic alphabeta T cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Valpha14Jalpha18 TCR in mice and Valpha24Jalpha18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR alpha chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where type II cells generally suppress tumor immunity while type I NKT cells can enhance anti-tumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell-targeted therapies for the treatment of cancer. PMID- 27393671 TI - Animal contributed papers. PMID- 27393672 TI - Plant contributed papers. PMID- 27393673 TI - Animal posters. PMID- 27393675 TI - Invertebrate posters. PMID- 27393674 TI - Education poster and high school award winning silent abstracts. PMID- 27393677 TI - Plenary Symposium: Molecular Nutrition. PMID- 27393676 TI - Plant posters. PMID- 27393678 TI - Modelling the interaction between bacteriophages and their bacterial hosts. AB - A mathematical model simulating the interaction between bacteriophages and their bacterial hosts has been developed. It is based on other known models describing this type of interaction, enhanced with an ability to model the system influenced by other environmental factor such as pH and temperature. This could be used for numerous estimations of growth rate, when the pH and/or the temperature of the environment are not constant. The change of pH or the temperature greatly affects the specific growth rate which has an effect on the final results of the simulation. Since the model aims on practical application and easy accessibility, an interactive website has been developed where users can run simulations with their own parameters and easily calculate and visualise the result of simulation. The web simulation is accessible at the URL http://www.phisite.org/model. PMID- 27393679 TI - [Not Available]. PMID- 27393680 TI - [Not Available]. AB - The increased incidence of dementia on the aging population makes this disease a major public health problem. Among known causes of dementia, drug etiology is under considered. We investigated the relationship between exposure to drug therapy and dementia with a case/non-case study using reports of the French Pharmacovigilance database. Among 263 962 adverse effects recorded between 1985 and 2005, 79 (0.03%) are dementia. Median age is 66 (range 3-91). There was 41 women and 37 men. The therapeutic drug class associated with dementia were anticonvulsants, antiparkinsonians, antidepressants, anxiolytics, hypnotics, antipsychotics and morphinics. An association between reporting of dementia and non neurotropic drugs were also found, i.e. interferon alfa-2B, vancomycin and allopurinol. The term "Dementia" is only mentioned in the summary of the characteristics of valproate, but it may concern other drugs. Drug etiology for dementia is a reality but is not necessarily attributed as a cause in aging population, in particular. PMID- 27393681 TI - A Luminex-based single DNA fragment amplification assay as a practical tool for detecting and serotyping dengue virus. AB - Dengue is a mosquito-borne viral infection that can evolve from subclinical to severe forms of disease. Early recognition during initial primary and secondary infections correlates with a reduced case-fatality rate in susceptible groups. The aim of this study was to standardize a DNA hybridization assay based on the Luminex technology for detecting and serotyping dengue virus (DENV). Reference DENVs representing the four different serotypes were used as controls to standardize the test. For validation, 16 DENV isolates obtained from a reference laboratory were analyzed in a double-blind manner to validate the test. Sixty blood samples from patients suspected of having dengue fever were used to evaluate the methodology after the validation step, and the results were compared with the reference semi-nested RT-PCR. Additionally, five human samples of each Zika and Chikungunya confirmed patients were used for specificity analysis. The Luminex-based assay correctly identified all 16 DENV isolates. In the evaluation step, the results of the RT-PCR/Luminex assay showed a concordance of 86.7% with those of the semi-nested RT-PCR. None of other virus infection samples was amplified. This is the first description of a hybridization assay that can discriminate the four DENV serotypes using probes against a single DENV sequence. The results indicated that the RT-PCR/Luminex DENV assay designed and evaluated in this study is a valuable additional tool for the early and rapid detection and serotyping of DENV, which could, in the future, be applied to new targets such as the Zika and Chikungunya viruses. PMID- 27393682 TI - Phospholipid vesicles encapsulated bacteriophage: A novel approach to enhance phage biodistribution. AB - Phage therapy has been at the centre of attraction for combating multi-drug resistant strains. However, less stability and rapid clearance of phage by mononuclear phagocytic system (MPS) restricts its use in humans. In the present study, aim was to develop a liposomal delivery system for bacteriophage that can assure efficient phage delivery and retention at the site of infection. Different ratios of cholesterol, lipids and surfactant along with different charge inducers were employed to prepare liposomes. Phage was then entrapped in the liposomes and characterized on the basis of morphology, size, entrapment efficiency and stability. Further, in vivo biodistribution of free phage and liposome entrapped phage was compared in different organs of mice. A cationic liposomal formulation showed maximum encapsulation efficiency of 92%. Transmission electron microscopy (TEM) confirmed the entrapment of phages in liposomes. Liposome preparation was found to be most stable at 4 degrees C during storage. Liposome entrapped bacteriophage was retained for longer duration in different organs i.e. upto day 4 in blood, day 6 in liver, lungs and kidney, 14days in spleen of mice as compared to free phage that became undetectable by 36th h in blood as well as lungs and by 48th h in all other organs. PMID- 27393683 TI - Estimating the concentration of urea and creatinine in the human serum of normal and dialysis patients through Raman spectroscopy. AB - Urea and creatinine are commonly used as biomarkers of renal function. Abnormal concentrations of these biomarkers are indicative of pathological processes such as renal failure. This study aimed to develop a model based on Raman spectroscopy to estimate the concentration values of urea and creatinine in human serum. Blood sera from 55 clinically normal subjects and 47 patients with chronic kidney disease undergoing dialysis were collected, and concentrations of urea and creatinine were determined by spectrophotometric methods. A Raman spectrum was obtained with a high-resolution dispersive Raman spectrometer (830 nm). A spectral model was developed based on partial least squares (PLS), where the concentrations of urea and creatinine were correlated with the Raman features. Principal components analysis (PCA) was used to discriminate dialysis patients from normal subjects. The PLS model showed r = 0.97 and r = 0.93 for urea and creatinine, respectively. The root mean square errors of cross-validation (RMSECV) for the model were 17.6 and 1.94 mg/dL, respectively. PCA showed high discrimination between dialysis and normality (95 % accuracy). The Raman technique was able to determine the concentrations with low error and to discriminate dialysis from normal subjects, consistent with a rapid and low-cost test. PMID- 27393684 TI - Food consumption of children younger than 6 years according to the degree of food processing. AB - OBJECTIVE: To evaluate food intake according to the degree of processing, stratified by family income and age, in a representative sample of children younger than 6 years in the city of Pelotas, RS, Brazil. METHODS: Cross-sectional population-based study carried out with 770 children aged 0-72 months of age living in the urban area of Pelotas. The dietary intake of children was assessed by 24-h recall administered to mothers or guardians. The energy intake was estimated and each food item was classified according to the food processing degree. Food consumption was stratified by age (younger than 24 months; 24 months or older) and associations between quintiles of family income and relative contribution of each food to total energy were performed by linear regression. The Wald test was applied to test linear trend across groups. RESULTS: The mean energy intake was 1725.7kcal/day. The mean contribution of processed and ultraprocessed foods was 19.7% among children younger than 24 months and 37% in those aged 24 months or older, while the mean consumption of natural and minimally processed food was 61% and 44%, respectively. Among children aged 24 months or older, a greater consumption of canned foods, cheese and sweets was observed as family income quintiles increased, while breads were more consumed by those children belonging to the lower income quintiles. CONCLUSION: A high caloric contribution of ultraprocessed foods in detriment to a lower consumption of natural and minimally processed foods was observed in the diet of children younger than 6 years. PMID- 27393685 TI - Daily meal frequency and associated variables in children and adolescents. AB - OBJECTIVE: To investigate the frequency distribution of daily meals and its relation to demographic, socioeconomic, behavioral, anthropometric and biochemical factors in children and adolescents. METHODS: This was a cross sectional study with a representative sample of 708 schoolchildren aged 7-14 years. Data on personal information, socioeconomic status, physical activity and number of meals were obtained through semi-structured questionnaire and consumption by 24-h recall and food record. Weight and height measurements were also performed to calculate the body mass index. Finally, blood samples were collected for analysis of total cholesterol, high- and low density lipoprotein, triglyceride, and glucose levels. Descriptive statistics, the Mann-Whitney test, and Poisson regression were used in statistical analysis. RESULTS: Meal frequency <4 was associated in children, family income <3 Brazilian minimum wages (PR=5.42; 95% CI: 1.29-22.77; p=0.021) and adolescents, the number of sons in the family >2 (PR=1.53; 95% CI: 1.11-2.11; p=0.010). Even in the age group of 10-14 years, <4 meals was related to higher prevalence of body mass index (PR=1.33; 95% CI: 1.02 1.74; p=0.032) and low-density lipoprotein (PR=1.39; 95% CI: 1.03-1.87; p=0.030) higher after adjustments. CONCLUSION: Lower frequency of meals was related to lower income in children and adolescents, larger number of sons in the family, and increased values of body mass index and low-density lipoprotein. PMID- 27393686 TI - Safe and easy access technique for the first trocar in laparoscopic surgery. AB - BACKGROUND: Access-related injuries are still an important consideration and may increase morbidity and mortality. This study aimed to present in detail a safe and easy technique for open insertion of the first trocar. PATIENTS AND METHODS: This technique has been used routinely in the vast majority of laparoscopic procedures at first author's department since 1998. The data were collected prospectively and analyzed retrospectively for the 11-year period of January 2005 through December 2015. The primary site of access is the umbilicus, but this technique can be used for all insertion points. RESULTS: A total of 2579 laparoscopic surgical interventions were performed. The abdominal access was established in 2252 patients in open and in 321 cases with blind puncture using a Veress needle. There were three cases (0.9 %) of accidental injuries with blind puncture and two cases (0.09 %) with open technique. Injuries sustained with open technique injuries were less severe and immediately discernable. None of the patients were converted to open technique. CONCLUSION: The method can be used easily and rapidly, even in obese patients. It is safer than blind puncture and reduces costs. PMID- 27393687 TI - iRhom2 (Uncv) mutation blocks bulge stem cells assuming the fate of hair follicle. AB - iRhom2 is necessary for maturation of TNFalpha-converting enzyme, which is required for the release of tumor necrosis factor. In the previous study, we found that the iRhom2 (Uncv) mutation in N-terminal cytoplasmic domain-encoding region (iRhom2 (Uncv) ) leads to aberrant hair shaft and inner root sheath differentiation, thus results in a hairless phenotype in homozygous iRhom2 (Uncv/Uncv) BALB/c mice. In this study, we found iRhom2 mutation decreased hair matrix proliferation, however, iRhom2 (Uncv/Uncv) mice displayed hyperproliferation and hyperkeratosis in the interfollicular epidermis along with hypertrophy in the sebaceous glands. The number of bulge SCs was not altered and the hair follicle cycle is normal in iRhom2 (Uncv/Uncv) mice. The decreased proliferation in hair matrix but increased proliferation in epidermis and sebaceous glands in iRhom2 (Uncv/Uncv) mice may implying that iRhom2 (Uncv) mutation blocks bugle stem cells assuming the fate of hair follicle. This study identifies iRhom2 as a novel regulator for determination of keratinocyte lineages. PMID- 27393688 TI - Thoracic aortic dissection and heritability: forensic implications. PMID- 27393689 TI - Comparative Analysis of Human Nucleoside Kinase-Based Reporter Systems for PET Imaging. AB - PURPOSE: Radionuclide-based reporter gene imaging has the sensitivity to monitor gene- and cell-based therapies in human subjects. Potential immunogenicity of current viral transgenes warrants development of human-based reporter systems. We compared human nucleoside kinase reporters to a panel of nucleoside analogs of FEAU, FMAU, and FIAU, including the first in vivo assessment of L-[18F]FEAU. PROCEDURES: Human isogenic U87 cell lines were transduced to express different human reporter genes including dCK-R104M/D133A (dCKDM), dCK-R104Q/D133N (dCKep16A), dCK-A100V/R104M/D133A (dCK3M), and TK2-N93D/L109F (TK2DM), and wild type dCK (dCK) and herpes simplex virus type-1 (HSVTK) reporter gene as references. In vitro cell uptake assays were performed with [18F]FEAU, L [18F]FEAU, [14C]FMAU, L-[18F]FMAU, and [124I]FIAU. Micro-positron emission tomography/X-ray computed tomography imaging of xenograft-bearing nu/nu mice was conducted with [18F]FEAU, L-[18F]FEAU, L-[18F]FMAU, and [124I]FIAU on consecutive days. A cell viability assay was also performed to assess sensitivities to gemcitabine and bromovinyldeoxyuridine (BVdU). RESULTS: In vitro, dCKep16A and dCKDM with [18F]FEAU exhibited the highest sensitivity and selectivity of the human reporters, second only to HSVTK/[18F]FEAU. L-[18F]FEAU biodistribution in mice was on par with [18F]FEAU and L-[18F]FMAU. L-[18F]FMAU uptake in isogenic xenografts was highest for all human reporter genes. However, [18F]FEAU was the most selective of the short half-life reporter probes due to its minimal recognition by human dCK and relative sensitivity, whereas [124I]FIAU permitted imaging at a later time point, improving signal-to-background ratio. Of the human reporter genes, dCKep16A consistently outperformed the other tested reporters. Reporter genes of interest increased potency to the nucleoside analog prodrugs gemcitabine and BVdU. CONCLUSIONS: We demonstrate that human nucleoside kinase reporter systems vary significantly in their sensitivity and selectivity for in vivo imaging. The sufficiently high signal-to-background ratios and enhanced suicide gene potential support clinical translation. PMID- 27393690 TI - Chromobacterium rhizoryzae sp. nov., isolated from rice roots. AB - A novel facultatively anaerobic, rod-shaped bacterium, designated LAM1188T, was isolated from the roots of rice (Oryzasativa) in Hubei Province. Cells of LAM1188T were Gram-stain-negative and motile. The temperature and pH ranges for growth were 15-40 degrees C (optimum: 30 degrees C) and pH 5-10 (optimum: pH 7), respectively. The strain did not require NaCl for growth but tolerated up to 3.5 % NaCl (w/v). Analysis of the 16S rRNA gene sequence indicated that the isolate represented a member of the genus Chromobacterium, and was most closely related to Chromobacterium haemolyticum MDA0585T and Chromobacterium aquaticum CC SEYA-1T with 98.7 % and 97.3 % sequence similarity, respectively. The values of DNA-DNA hybridization between LAM1188T and C. haemolyticum JCM 14163T and C. aquaticum CCUG 55175T were 54.0+/-2.1 % and 44.0+/-1.2 %, respectively. The major cellular fatty acids were C16 : 0 and summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c). The main polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, four unidentified aminolipids and four unidentified lipids. The respiratory quinone was ubiquinone Q-8. The DNA G+C content was 64.1 mol% as determined by the Tm method. On the basis of its phenotypic, chemotaxonomic and phylogenetic characteristics, strain LAM1188T is suggested to represent a novel species of the genus Chromobacterium, for which the name Chromobacte riumrhizoryzae sp. nov. is proposed. The type strain is LAM1188T (=ACCC 19900T=JCM 31180T). PMID- 27393692 TI - Author's reply to letter from Dr. Ahmed Al-Badr on: "Trends in the aetiology of urogenital fistula: a case of 'retrogressive evolution'?". PMID- 27393693 TI - Urogynecology digest : Presented by Derrick J. Sanderson. PMID- 27393691 TI - Synuclein expression in the lizard Anolis carolinensis. AB - The synuclein (syn) family comprises three proteins: alpha-, beta- and gamma syns. In humans, they are involved in neurodegenerative diseases such as Parkinson's disease and in tumors. Members of the syn family were sequenced in representative species of all vertebrates and the comparative analysis of amino acid sequences suggests that syns are evolutionarily conserved, but information about their expression in vertebrate lineages is still scarce and completely lacking in reptiles. In this study, the expression of genes coding for alpha-, beta- and gamma-syns was analyzed in the green lizard Anolis carolinensis by semiquantitative RT-PCR and Western blot. Results demonstrate good expression levels of the three syns in the lizard nervous system, similarly to human syns. This, together with the high identity between lizard and human syns, suggests that these proteins fulfill evolutionarily conserved functions. However, differences between lizard and humans in the expression of syn variants (two different variants of gamma-syn were detected in A. carolinensis) and differences in some amino acids in key positions for the regulation of protein conformation and affinity for lipid and metal ions also suggest that these proteins may have acquired different functional specializations in the two lineages. PMID- 27393695 TI - Trends in the aetiology of urogenital fistula: a case of "retrogressive evolution"? PMID- 27393694 TI - Levator ani defects in patients with stress urinary incontinence: three dimensional endovaginal ultrasound assessment. AB - INTRODUCTION AND HYPOTHESIS: To determine the prevalence of levator ani (LA) muscle subdivision defects in patients with SUI using three-dimensional endovaginal ultrasound (3D EVUS). METHODS: This is a prospective cohort study of 100 patients with pure or predominant urodynamic SUI who underwent 3D EVUS. The 3D cubes obtained were analyzed and the LA muscle was divided into three subgroups: the puboperinealis/puboanalis, the puborectalis, and the iliococcygeus/pubococcygeus. Each LA muscle subdivision was individually scored on each side (0: no defect, 1: <=50 % muscle loss, 2: > 50 % muscle loss, and 3: total absence of the muscle) and a cumulative score, categorized as 0 (no defect), mild (total score 1-6), moderate (7-12), and severe (>=13) was calculated. RESULTS: The number of women with no LA muscle defect or a mild defect was significantly higher than the number of those with a moderate or severe defect (p < 0.001). Apart from the small inverse relationship of the total puborectalis muscle score and the cumulative subdivision score with maximal urethral closure pressure (r value > -0.3; p < 0.05), the muscle defect scores were not found to correlate with urodynamic parameters (p > 0.05). Although all muscle subdivisions contributed to the overall LA muscle defect score, the association was strongest for the puborectalis component (r = 0.9; p < 0.001). The prevalence of the LA muscle defect in patients with intrinsic sphincter deficiency (ISD) was not significantly different from that in patients without ISD. CONCLUSION: Patients with SUI have a higher prevalence of no or mild LA defect compared with a moderate or severe LA defect. PMID- 27393696 TI - Devosia confluentis sp. nov., isolated from the junction between the ocean and a freshwater lake, and reclassification of two Vasilyevaea species as Devosia enhydra comb. nov. and Devosia mishustinii comb. nov. AB - A Gram-stain-negative, aerobic, non-flagellated and pleomorphic bacterium, designated HJR-2T, was isolated from a junction between the ocean and a freshwater lake on the East Sea, South Korea. It grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 0-1.5 % (w/v) NaCl. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain HJR-2T clustered with the type strains of Vasilyevaea enhydra and Vasilyevaea mishustinii and this cluster fell within the clade comprising the type strains of Devosia species. Strain HJR-2T exhibited 16S rRNA gene sequence similarity values of 97.2 and 97.0 % to the type strains of V. enhydra and V. mishustinii, respectively, and 93.9 96.2 % to the type strains of Devosia species. Strain HJR-2T contained Q-10 as the predominant ubiquinone and C18 : 1omega7c, 11-methyl C18 : 1omega7c and C16 : 0 as major fatty acids. Major polar lipids of strain HJR-2T were phosphatidylglycerol and two unidentified glycolipids. The DNA G+C content was 66.0 mol% and its mean DNA-DNA relatedness values with the type strains of V. enhydra and V. mishustinii were 11-17 %. Differential phenotypic properties, together with its phylo genetic and genetic distinctiveness, revealed that strain HJR-2T is separated from V. enhydra, V. mishustinii and Devosia species. On the basis of the data presented, strain HJR-2T (=KCTC 52211T=NBRC 112271T) is considered to be the type strain of a novel species of the genus Devosia, for which the name Devosiaconfluentis sp. nov. is proposed. In this study, it is also proposed that V. enhydra and V. mishustinii be reclassified as members of the genus Devosia. PMID- 27393698 TI - Withdrawal of Antidementia Drugs in Older People: Who, When and How? AB - The evidence base to guide withdrawal of antidementia medications in older people with dementia is limited; while some randomised controlled studies have considered discontinuation of cholinesterase inhibitors (ChEIs), no such studies examining discontinuation of the N-methyl-D-aspartate receptor antagonist memantine have been conducted to date. The purpose of this opinion article was to summarise the existing evidence on withdrawal of cholinesterase inhibitors and memantine, to highlight the key considerations for clinicians when making these prescribing decisions and to offer guidance as to when and how treatment might be discontinued. Until the evidence base is enhanced by the findings of large-scale, randomised controlled discontinuation trials of ChEIs and memantine that use multiple, clinically relevant, cognitive, functional and behavioural outcome measures, clinicians' prescribing decisions involve balancing the risks of discontinuation with side effects and costs of continued treatment. Such decisions must be highly individualised and patient-centred. PMID- 27393697 TI - A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1. AB - AIMS: The primary objective was to demonstrate that basal insulin peglispro (BIL) was non-inferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%. MATERIALS AND METHODS: IMAGINE 1 was a Phase 3, open-label, parallel-arm study conducted in nine countries. Adults with type 1 diabetes (n = 455) were randomized (2:1) to bedtime BIL or GL in combination with prandial insulin lispro for 78 weeks, with a primary endpoint of 26 weeks. An electronic diary facilitated data capture and insulin dosing calculations for intensive insulin management. RESULTS: At 26 weeks, mean HbA1c was 7.06% +/- 0.04% and 7.43% +/- 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: -0.50 to -0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and between-day fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations >=3 * ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted. PMID- 27393699 TI - Airway Microbiota and the Implications of Dysbiosis in Asthma. AB - The mucosal surfaces of the human body are typically colonized by polymicrobial communities seeded in infancy and are continuously shaped by environmental exposures. These communities interact with the mucosal immune system to maintain homeostasis in health, but perturbations in their composition and function are associated with lower airway diseases, including asthma, a developmental and heterogeneous chronic disease with various degrees and types of airway inflammation. This review will summarize recent studies examining airway microbiota dysbioses associated with asthma and their relationship with the pathophysiology of this disease. PMID- 27393700 TI - What Ancestry Can Tell Us About the Genetic Origins of Inter-Ethnic Differences in Asthma Expression. AB - Differences in asthma prevalence have been described across different populations, suggesting that genetic ancestry can play an important role in this disease. In fact, several studies have demonstrated an association between African ancestry with increased asthma susceptibility and severity, higher immunoglobulin E levels, and lower lung function. In contrast, Native American ancestry has been shown to have a protective role for this disease. Genome-wide association studies have allowed the identification of population-specific genetic variants with varying allele frequency among populations. Additionally, the correlation of genetic ancestry at the chromosomal level with asthma and related traits by means of admixture mapping has revealed regions of the genome where ancestry is correlated with the disease. In this review, we discuss the evidence supporting the association of genetic ancestry with asthma susceptibility and asthma-related traits, and highlight the regions of the genome harboring ancestry-specific genetic risk factors. PMID- 27393702 TI - The Soul in Medicine: Rabbinic and Scientific Controversies. AB - The practice of medicine relies on a combination of two very different sources, and requires two kinds of talents: a cognitive-instrumental, knowledge-based and disease-centered approach; and a psychological, expressive-relational and patient centered approach. Throughout the centuries, the mix between the cognitive and expressive dimensions, and the relative emphasis given to each approach, has varied considerably. Current evidence-based medicine privileges the cognitive performative dimension. The recent developments within medicine are indicative of the inherent and lasting tension between the cognitive and expressive dimensions. Not surprisingly, then, related terms of debate are also apparent in medieval rabbinic discussions of medical practice. However, the rabbinic and medical traditions resolved the tension in very different ways. This paper explores a conceptual link between the modern dynamics of the cognitive and the socio relational dimensions, and a complementary rabbinic controversy starting in the thirteenth century, originally between Maimonides and Nahmanides, both physicians. There are significant interactions between the modern evolution in the roles of doctors and patients, and the rabbinic approaches to physicians and illness. The mapping of the two debates about doctors and patients suggests that the tension between science and soul, and the dynamics of integrating them, has characterized medicine through the ages, though they can lead to different outcomes. PMID- 27393701 TI - Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation. AB - The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation. Here, we discuss the current concept of eosinophil ETosis which provides a new look at eosinophilic inflammation. Lessons from eosinophilic chronic rhinosinusitis revealed that ETosis-derived DNA traps, composed of stable web like chromatin, contribute to the properties of highly viscous eosinophilic mucin and impairments in its clearance. Intact granules entrapped in DNA traps are causing long-lasting inflammation but also might have immunoregulatory roles. Eosinophils possess a way to have post-postmortem impacts on innate immunity, local immune response, sterile inflammation, and tissue damage. PMID- 27393703 TI - A 15-Year Review of Trends in Representation of Female Subjects in Islamic Bioethics Research. AB - Gender representation in Islamic bioethics research in the twenty-first century has not been studied. To study temporal trends in representation of female subjects in Islamic bioethics research, PubMed-listed publications on Islamic bioethics from years 2000 to 2014 were reviewed for gender participation in human subjects' research. There were temporal trends of increasing publications of Islamic bioethics-related human subjects' research (64 papers over 15 years; R 2 = 0.72; p < 0.0004). Female subjects were well represented with a trend toward increasing participation. This was true for women from Muslim-majority countries even in non-gender-focused studies over the past 15 years. PMID- 27393704 TI - The Effect of Holy Qur'an Recitation on Depressive Symptoms in Hemodialysis Patients: A Randomized Clinical Trial. AB - Patients with advanced renal failure often face considerable sociopsychological stress as a result of lifestyle changes due to the disease and its treatment. The aim of the present study is to examine the effect of the Holy Qur'an recitation on depressive symptoms in hemodialysis patients. In this clinical trial, 54 hemodialysis patients were randomized to either an experimental (n = 27) or a control (n = 27) group. Patients completed the Beck Depression Inventory-II (BDI II) at baseline and at 1 month after the intervention. Participants in the experimental group listened to recitation of the Holy Qur'an, while those in the control group received no intervention. The mean BDI-II score at baseline was 33.6 (+/-6.7) for the experimental group and 29.3 (+/-9.0) for the control group; at the end of treatment, BDI-II scores in the experimental and control groups were 14.5 (+/-4.8) and 31.6 (+/-9.2), respectively. Results from the repeated measures general linear model controlling for baseline differences indicated a significant treatment effect (F = 9.30, p = 0.004, Cohen's d = 0.85). Holy Qur'an recitation has a significant effect on lowering depressive symptoms in hemodialysis patients. Holy Qur'an recitation is an easy-to-implement and cost effective strategy that may be used to supplement the treatment of depression in this setting in Iran. PMID- 27393706 TI - Dental student self-assessment of a medical history competency developed by Oral and Maxillofacial Surgery Faculty. AB - PURPOSE: To develop a standardized competency exam to evaluate dental student knowledge of patients with complex medical histories. Analysis was performed to determine if there is a difference between dental student self-assessment of the exam compared to oral surgery faculty. The overall goal is to enhance student comprehension of advanced medical patients in the pre-doctoral oral and maxillofacial surgery clinic and make changes based on student responses. METHODS: The exam took place in a simulation laboratory containing two-way mirrors where the student could not see the evaluator. Three standardized patients (trained actors) were given different medical history scenarios to learn prior to the exam. Students were randomly assigned to interview one patient. The graders consisted of senior and junior level faculty. In real time (live) randomized manner, faculty assessed each student using a standardized rubric to assign a score of 1 to 4. Immediately afterwards, students assessed their own performance using the same scale. RESULTS: Students gave themselves significantly higher grades (P < 0.001) on the exam (10.7 +/- 0.12) compared to the faculty (9.2 +/- 0.17). There was no significant difference in student (P = 0.16) or faculty assessment (P = 0.29) between the three different medical scenarios. There was no significant difference between faculty in assessment of student performances (P = 0.16). CONCLUSION: These results suggested that students overestimated their performance compared to the faculty assessment. This could be due to that students assessed their performance based on memory and self confidence; that exceeds their expectations. Internal calibration of student performances and faculty grading using standardized criteria may produce more accurate and reliable outcomes in student scoring. PMID- 27393705 TI - Dual Inhibition of PI3K/Akt and mTOR by the Dietary Antioxidant, Delphinidin, Ameliorates Psoriatic Features In Vitro and in an Imiquimod-Induced Psoriasis Like Disease in Mice. AB - AIM: The treatment of psoriasis remains elusive, underscoring the need for identifying novel disease targets and mechanism-based therapeutic approaches. We recently reported that the PI3K/Akt/mTOR pathway that is frequently deregulated in many malignancies is also clinically relevant for psoriasis. We also provided rationale for developing delphinidin (Del), a dietary antioxidant for the management of psoriasis. This study utilized high-throughput biophysical and biochemical approaches and in vitro and in vivo models to identify molecular targets regulated by Del in psoriasis. RESULTS: A kinome-level screen and Kds analyses against a panel of 102 human kinase targets showed that Del binds to three lipid (PIK3CG, PIK3C2B, and PIK3CA) and six serine/threonine (PIM1, PIM3, mTOR, S6K1, PLK2, and AURKB) kinases, five of which belong to the PI3K/Akt/mTOR pathway. Surface plasmon resonance and in silico molecular modeling corroborated Del's direct interactions with three PI3Ks (alpha/c2beta/gamma), mTOR, and p70S6K. Del treatment of interleukin-22 or TPA-stimulated normal human epidermal keratinocytes (NHEKs) significantly inhibited proliferation, activation of PI3K/Akt/mTOR components, and secretion of proinflammatory cytokines and chemokines. To establish the in vivo relevance of these findings, an imiquimod (IMQ)-induced Balb/c mouse psoriasis-like skin model was employed. Topical treatment of Del significantly decreased (i) hyperproliferation and epidermal thickness, (ii) skin infiltration by immune cells, (iii) psoriasis-related cytokines/chemokines, (iv) PI3K/Akt/mTOR pathway activation, and (v) increased differentiation when compared with controls. Innovation and Conclusion: Our observation that Del inhibits key kinases involved in psoriasis pathogenesis and alleviates IMQ-induced murine psoriasis-like disease suggests a novel PI3K/AKT/mTOR pathway modulator that could be developed to treat psoriasis. Antioxid. Redox Signal. 26, 49-69. PMID- 27393707 TI - Pain management in photodynamic therapy using a nitrous oxide/oxygen mixture: a prospective, within-patient, controlled clinical trial. AB - BACKGROUND: Photodynamic therapy is an effective treatment for actinic keratoses. Nevertheless, severe pain during the procedure is a serious adverse effect, which leads to interruption or even termination. Complete pain relief remains a difficult challenge. OBJECTIVE: To evaluate the effect of a nitrous oxide/oxygen mixture on pain intensity during photodynamic therapy. METHODS: This clinical trial has been designed as a prospective, single-centre, explorative, controlled, observational study. RESULTS: We were able to detect a significant overall pain reduction of 55.2% after application of a nitrous oxide/oxygen mixture by means of an intra-individual comparison. Furthermore, the total number of therapy interruption significantly decreased by 82% after the inhalation analgesia. Additionally, treatment satisfaction ranged from 'extremely to very satisfied'. CONCLUSIONS: This study shows that analgesia by means of a nitrous oxide/oxygen mixture is a very effective and well-tolerated method for achieving significant pain reduction during photodynamic therapy. PMID- 27393708 TI - Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis: Differences Revealed Between Epithelial Cells from Nasal Polyps and Inferior Turbinates. AB - The pathogenesis of chronic rhinosinusitis (CRS) remains unclear to date. The tissue remodeling in nasal polyps may be the result of inflammatory mediators and may involve epithelial-mesenchymal transition (EMT) and EMT-associated features such as cell motility in nasal epithelial cells (NECs). We determined whether NEC in nasal polyps of CRS already display features of EMT in vivo or respond with EMT to growth factor stimulation in vitro. Nasal polyp tissues expressed both epithelial and mesenchymal markers. Primary NEC from inferior turbinates and nasal polyps responded to the EMT-inducing agents transforming growth factor (TGF)-beta1 and epidermal growth factor (EGF) with different expression patterns of EMT markers (E-cadherin, N-cadherin, Snail, Slug, Twist), however, only NEC from nasal polyps were susceptible to TGF-beta1 and EGF-dependent cell migration. Our data suggest that a partial EMT is associated with the pathogenesis of nasal polyps in CRS patients. Furthermore, we show for the first time that epithelial cells from both nasal polyps and inferior turbinates were able to undergo an EMT like process following exposure to TGF-beta1 or EGF in vitro but that only NEC from nasal polyps responded with enhanced cell motility. Our data suggest that NEC from CRS patients have undergo partial EMT and that this process may be involved in the pathogenesis of CRS. PMID- 27393709 TI - Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance. AB - STUDY OBJECTIVE: To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (ADHF) and loop diuretic resistance. DESIGN: Retrospective cohort study. SETTING: Large urban academic medical center. PATIENTS: Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis. MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide-type diuretic administration) was higher in the chlorothiazide group (mean +/- SD 318.9 +/- 127.7 vs 268.4 +/- 97.6 mg/day in the metolazone group, p=0.004), but net UOP was similar (mean +/- SD 877.0 +/- 1189.0 ml in the chlorothiazide group vs 710.6 +/- 1145.9 ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491 +/- 282 mg and 5.8 +/- 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 +/- 1443.0 ml vs 2030.2 +/- 1725.0 ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6 +/- 1517.4 ml versus 1397.6 +/- 1370.7 ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups. CONCLUSION: Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first-line option in this patient population. PMID- 27393710 TI - A Tutorial on Pharmacodynamic Scripting Facility in Simcyp. PMID- 27393711 TI - Onionin A, a sulfur-containing compound isolated from onions, impairs tumor development and lung metastasis by inhibiting the protumoral and immunosuppressive functions of myeloid cells. AB - SCOPE: Recent studies have demonstrated that myeloid lineage cells, such as macrophages and myeloid suppressor cells (MDSCs), are major components exhibiting protumoral functions in the setting of tumor progression. Tumor-associated macrophages polarized to the protumoral M2 phenotype promote tumor proliferation and are considered to be a therapeutic target in patients with malignant tumors. METHODS AND RESULTS: We identified a new candidate compound, called onionin A (ONA) isolated from onions, that inhibits macrophage polarization into the M2 phenotype, as well as the immunosuppressive activity of MDSCs and tumor proliferation, by suppressing signal transducer and activator of transcription-3 (Stat3) activation. Furthermore, ONA administration was found to significantly suppress subcutaneous tumor development and lung metastasis in tumor-bearing mice. ONA administration also inhibited Stat3 activation and increased the number of infiltrating lymphocytes in tumor tissues, and an ex vivo analysis showed that the immunosuppressive effect of MDSCs in tumor-bearing mice is impaired by ONA. Moreover, ONA regulated tumor proliferation by inhibiting cell-cell interactions between macrophages and tumor cells, and ONA administration enhanced the antitumor effects of cisplatin in the tumor-bearing mice. CONCLUSIONS: These findings demonstrate that ONA may be a potential new tool for antitumor therapy and also for tumor prevention. PMID- 27393713 TI - [Not Available]. PMID- 27393712 TI - Serum asymmetric dimethylarginine and arginine levels predict microvascular and macrovascular complications in type 2 diabetes mellitus. AB - BACKGROUND: Increased oxidative stress in diabetes increases nitric oxide (NO) oxidation and low l-arginine (Arg) could further reduce NO and impair vascular function, thereby accelerating, in the long run, vascular complications. We therefore measured Arg and asymmetric dimethylarginine (ADMA) levels in patients with type 2 diabetes mellitus (T2DM) and healthy controls. Additionally, we observed the diabetic individuals over time to see if Arg and asymmetric dimethylarginine predicted T2DM complications. METHODS: We examined baseline serum Arg and ADMA levels in a cohort of 105 participants with type 2 diabetes and compared them with an age- and weight-matched nondiabetic group of 137 individuals who served as a reference population. Additionally, we assessed whether Arg and/or ADMA predicted macrovascular and microvascular complications over 6 years of follow-up. RESULTS: Serum Arg was lower in individuals with T2DM than in controls (64 +/- 28 vs 75 +/- 31 MUmol/L; P = .009) and inversely related to hemoglobin A1c (r = -0.2; P = .002). Over follow-up, we observed that participants with T2DM in the lowest quartile of Arg had increased risk for the subsequent evolution of nephropathy, peripheral neuropathy, and composite microvascular complications (odds ratio [OR] = 5.5; 95% confidence interval [CI] 1.9 to 16; P = .002). The highest ADMA quartile was associated with increased risk for both microvascular (OR = 4.5; 95% CI -1.4 to 14.1; P = .009) and 6.5 year incident macrovascular complications (OR = 8.3; 95% CI 1.9-35.5; P = .004). CONCLUSION: l-Arginine levels are lower in individuals with T2DM than in matched controls. Both low Arg and high ADMA, independent of each other and adjusted for classical risk factors, predict the incidence of microvascular complications. PMID- 27393715 TI - [Not Available]. PMID- 27393714 TI - [Not Available]. AB - The assessment of a health technology is frequently accompanied by uncertainty about its impact, at short or long terms, on the health of the population. The Health Authorities may request additional " post-registration " data that will allow a relevant reassessment of these technologies. The responsibility to collect this information lies with the industry and the HAS evaluates the methodology. This guideline provides practical benchmarks on methodological aspects of these studies. It describes the different types of studies to consider depending on the objectives, including the use of databases and cohorts and European studies. It emphasizes the importance of establishing a scientific committee, clearly defining the objectives of the study, justifying the methodological choices, documenting the representativeness or completeness of centers, investigators and patients, limiting the number of lost of follow-up patients and missing data, describing the statistical analysis methods, the bias and their possible impact on results. The publication of the results of these studies is strongly encouraged. PMID- 27393716 TI - Burden of preoperative cardiovascular disease risk factors on breast cancer surgery outcomes. AB - BACKGROUND: Cardiovascular comorbidities have been studied sporadically in breast cancer surgery. No study has provided a comprehensive assessment of the severity and relative influence of preoperative cardiac risk factors on surgical outcomes. METHODS: 78,338 breast cancer surgery patients were identified from the 2006 to 2012 National Surgical Quality Improvement Program (NSQIP) database. We estimated the impact of chronic conditions (diabetes, hypertension, obesity, smoking), acute cardiac events (myocardial infarction, congestive heart disease, angina), and past cardiac procedures (cardiac surgery, percutaneous coronary intervention) on 30-day postoperative complications, reoperation, and readmission. RESULTS: Nearly 65% of patients had chronic conditions, <1% had acute events, and 3% had past procedures. The prevalence of outcomes was low: 5% had complications, 4% underwent reoperation, and 4% were readmitted. Over 65% of complications were wound-related. All risk factor categories were associated with complications (ORs from 1.26 to 4.18). Acute events had the strongest effect on overall (OR 3.54, CI 2.55-4.91) and medical (OR 4.18, CI 2.73-6.41) complications. Chronic conditions and past procedures also predicted reoperation and readmission (ORs from 1.57 to 2.68). The odds of all outcomes increased with the number of chronic conditions (ptrend < 0.001). CONCLUSIONS: Cardiovascular disease has a significant impact on outcomes even in minimal-risk breast cancer surgery. J. Surg. Oncol. 2016;114:144-149. (c) 2016 Wiley Periodicals, Inc. PMID- 27393717 TI - Predictors of Hospital Readmission in Patients Receiving Outpatient Parenteral Antimicrobial Therapy. AB - STUDY OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used, and unfortunately, readmissions during OPAT are common. The purpose of this study was to identify predictors of hospital readmission among patients receiving OPAT. DESIGN: Retrospective cohort study. SETTING: Large academic tertiary care hospital. PATIENTS: A total of 216 adults who were discharged and received OPAT through a peripherally inserted central catheter for at least 2 days for treatment of an active infection, excluding patients with cystic fibrosis, between January 2012 and August 2013. Of these patients, 43 had hospital readmissions and 173 did not. MEASUREMENTS AND MAIN RESULTS: The median age of all study patients was 56 years. Common infections included bone and joint (32%), genital/urinary tract (16%), endocarditis (14%), central nervous system (9.7%), and pneumonia (9.7%). For the 43 patients (20%) who had readmissions, reasons for readmission were infection recurrence or progression (33%), adverse drug reactions (24%), central catheter-associated issues (16%), or non-OPAT related reasons (27%). In the multivariate analysis, patients assigned to a primary care physician were less likely to be readmitted (odds ratio [OR] 0.286, 95% confidence interval [CI] 0.115-0.711), whereas factors independently associated with an increased readmission rate included previous hospital admission in the past 12 months (OR 2.588, 95% CI 1.159-5.778), medical history of malignant lymphoma (OR 25.172, 95% CI 2.311-272.209), and increased planned OPAT duration (OR 1.058, 95% CI 1.034-1.082). CONCLUSION: Readmissions while patients received OPAT were common. Therefore, proactive interventions including primary care physician assignment to facilitate follow-up and communication should be implemented to decrease the risk of readmission, particularly in the identified high-risk populations. PMID- 27393718 TI - A 15-year experience with gastric neuroendocrine tumors: Does type make a difference? AB - BACKGROUND: Gastric neuroendocrine tumors (GNETs) are rare and classified into three types by disease etiology and typical behavior. METHODS: The aim was to describe outcomes after GNET resection at a single institution from 2000 to 2014, stratified by tumor type. Given the small patient number, P-values were not assigned. RESULTS: Of 22 patients, 12 patients (55%) had Type 1, none (0%) had Type 2, and 10 (45%) had Type 3 tumors. Compared to Type 3, Type 1 patients were younger (mean age: 52 vs. 59 years) with similar rates of endoscopic resection (25% vs. 20%). Type 1 GNETs often had multiple tumors (60% vs. 10%) and were not poorly differentiated (0% vs. 11%). Only 33% of Type 1 had nodal metastases compared to 71% of Type 3. Type 1 GNETs presented with metastatic disease less often (17% vs. 40%). Three year recurrence-free survival was 33% for Type 1 compared to 86% for Type 3. Disease-specific survival at 3-years was 100% and 75% for Types 1 and 3, respectively. CONCLUSION: Type 1 GNETs are often indolent and multifocal without nodal involvement, but have high recurrence risk. Type 3 is more aggressive with increased nodal involvement; nodal evaluation should be routinely performed. Determination of GNET type is paramount to treating patients with this rare disease. J. Surg. Oncol. 2016;114:576-580. (c) 2016 Wiley Periodicals, Inc. PMID- 27393719 TI - Patterns of Cattle Farm Visitation by White-Tailed Deer in Relation to Risk of Disease Transmission in a Previously Infected Area with Bovine Tuberculosis in Minnesota, USA. AB - The main objective of this study was to characterize spatial patterns of white tailed deer (Odocoileus virginianus) movement related to bovine tuberculosis (bTB) transmission risk to cattle in north-western Minnesota. Twenty-one adult deer (16 females and 5 males) were captured during winter (January-March) 2011 in areas adjacent to where an outbreak (2005-2009) of bTB occurred in deer and cattle. Deer were fitted with GPS collars programmed to collect deer location information every 90 min over a 15-month period. The exact locations of cattle, cattle feeding areas, and stored forage that were available to collared deer were assessed seasonally. In total, 47% (n = 9) of collared deer survived to the end of the study. Causes of mortality included wolves (n = 6), hunters (n = 1) and unknown (n = 2); additionally, 2 deer were censored due to collar malfunctions. Our results indicated that 5 deer (25%) had home ranges that included 6 cattle farms (20%). Most (77%) of the deer visits occurred in areas where cattle were present, with most visits (60%) from 00:00 to 06:00. March to May revealed the most farm visitations by deer (37%). This study provided baseline information regarding cattle-deer interactions critical to transmission of bTB in this region and suggested that risk mitigation practices should be implemented to separate wildlife and domestic livestock when feasible. PMID- 27393720 TI - Don't Do Different Things...Do Things Differently! Drug Development in Rare Diseases. AB - Although definitions of rare disease vary, most acknowledge that there are small numbers of affected patients compared with other conditions. Small numbers of patients, overlapping involvement of investigators as researchers and caregivers, as well as close relationships between researchers and manufacturers require a different pattern of drug development. Regulatory guidances for rare diseases are available, as well as ones for specific rare diseases. Maintaining drug supply for rare diseases also demands innovative approaches. PMID- 27393721 TI - Sex- and Age-Related Differences in the Clinical and Neuroimaging Characteristics of Patients With Spontaneous Intracranial Hypotension: A Records Review. AB - BACKGROUND: The significance of sex- and age-related differences in the clinical course of spontaneous intracranial hypotension (SIH) was investigated. METHODS: We retrospectively studied 40 consecutive patients (female:male = 28:12, median age 41.5 years) treated under clinical diagnoses of SIH satisfying the International Classification of Headache Disorders 3rd edition criteria, including 37 patients (92.5%) with diffuse pachymeningeal enhancement. The patients were divided into two groups by age and sex, and the clinical and neuroimaging findings in each group were investigated. RESULTS: Acute onset (female:male = 82.1%:50.0%, P = .042), severe headache (75.0%:41.7%, P = .045) occurred with higher frequency in females than in males, and SDH occurred with lower frequency in females than in males (28.6%:75.0%, P = .006). Duration until the consultation (2:14 days, P = .022), SDH thickness (0:7.1 mm, P = .001), and iter displacement (1.6:7.1 mm, P = .004) was greater in males. Acute onset (Younger [<=40 years]: older [>40 years] = 94.1%:56.5%, P = .012), occurred with higher frequency in younger patients, and duration until the consultation (1:5 days, P = .001), frequency of SDH (17.7%:60.9%, P = .010), SDH thickness (0:5.9 mm, P = .003), in older patients. All nine patients with thunderclap headache were female, with median age of 37 years. CONCLUSIONS: More severe clinical symptoms with acute onset were observed in females and younger patients of SIH. Comparatively rare subdural hygroma/hematoma on magnetic resonance imaging might result from the shorter duration to diagnosis in females and younger patients. KEY WORDS: spontaneous intracranial hypotension, sex, age, magnetic resonance imaging, thunderclap headache. PMID- 27393722 TI - Similar HbA1c reduction and hypoglycaemia with variable- vs fixed-time dosing of basal insulin peglispro in type 1 diabetes: IMAGINE 7 study. AB - AIMS: To compare 24-hour fixed-time basal insulin peglispro (BIL) dosing with 8- to 40-hour variable-time BIL dosing for glycaemic control and safety in patients with type 1 diabetes. Primary outcome was non-inferiority of BIL variable-time dosing compared with fixed-time dosing for glycated haemoglobin (HbA1c) change after 12-week treatment (margin = 0.4%). MATERIALS AND METHODS: This Phase 3, open-label, randomized, cross-over study (N = 212) was conducted at 20 centres in the United States. During the 12-week lead-in phase, patients received BIL daily at fixed-times. Two 12-week randomized cross-over treatment phases followed, where patients received BIL dosed at either fixed- or variable-times. During the 4-week safety follow-up, patients received conventional insulins. RESULTS: During the lead-in period, least-squares mean HbA1c decreased from 7.5% to 6.8%. For BIL, variable-time dosing was non-inferior to fixed-time dosing for HbA1c change [least-squares mean difference = 0.06%, 95% confidence interval (-0.01, 0.13)]. In both regimens, HbA1c increased slightly during the cross-over periods, but remained significantly below baseline. Variable- and fixed-time dosing regimens had similar rates of total hypoglycaemia (10.4 +/- 0.62 and 10.5 +/- 0.67 events/patient/30 days, P = .947) and nocturnal hypoglycaemia (1.3 +/- 0.11 and 1.5 +/- 0.13 events/patient/30days, P = .060). Comparable proportions of patients achieved HbA1c < 7.0% with variable- [91 (54.5%)] and fixed-time dosing [101 (60.5%)]. CONCLUSIONS: Treatment with BIL allows patients to use flexible dosing intervals from 8 to 40 hours. Glycaemic efficacy (HbA1c), glycaemic variability and hypoglycaemia are similar to fixed-time dosing, suggesting that BIL could potentially provide flexibility in dosing for patients who miss their daily basal insulin. PMID- 27393723 TI - A portrait of a sucker using landscape genetics: how colonization and life history undermine the idealized dendritic metapopulation. AB - Dendritic metapopulations have been attributed unique properties by in silico studies, including an elevated genetic diversity relative to a panmictic population of equal total size. These predictions have not been rigorously tested in nature, nor has there been full consideration of the interacting effects among contemporary landscape features, colonization history and life history traits of the target species. We tested for the effects of dendritic structure as well as the relative importance of life history, environmental barriers and historical colonization on the neutral genetic structure of a longnose sucker (Catostomus catostomus) metapopulation in the Kogaluk watershed of northern Labrador, Canada. Samples were collected from eight lakes, genotyped with 17 microsatellites, and aged using opercula. Lakes varied in differentiation, historical and contemporary connectivity, and life history traits. Isolation by distance was detected only by removing two highly genetically differentiated lakes, suggesting a lack of migration-drift equilibrium and the lingering influence of historical factors on genetic structure. Bayesian analyses supported colonization via the Kogaluk's headwaters. The historical concentration of genetic diversity in headwaters inferred by this result was supported by high historical and contemporary effective sizes of the headwater lake, T-Bone. Alternatively, reduced allelic richness in headwaters confirmed the dendritic structure's influence on gene flow, but this did not translate to an elevated metapopulation effective size. A lack of equilibrium and upstream migration may have dampened the effects of dendritic structure. We suggest that interacting historical and contemporary factors prevent the achievement of the idealized traits of a dendritic metapopulation in nature. PMID- 27393724 TI - The value of radial probe endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal lymph node metastasis from primary papillary thyroid cancer. PMID- 27393725 TI - [Not Available]. PMID- 27393726 TI - [Not Available]. AB - AIM: The general objective of this study was to agree an inventory of fixtures of clinical trials done in Dakar, in order to make recommendations to improve the quality of clinical trials in Senegal. METHOD: We have done a survey from mars to may 2007, with investigators of the two biggest Senegalese university teaching hospitals and to the pharmacy management and the ethical committee. RESULTS: Our key results showed: 1) a small participation rate of teachers to clinical trials (11 on 37 interviewed); 2) that the principal sponsor is pharmaceutical industry; 3) that most of investigators have not degree in clinical trials; 4) that most pathologies concerned were malaria and AIDS; 5) that there are regulations related to clinical trials in Senegal. CONCLUSION: This study shows the necessity to integrate, in Senegal, clinical trials in the curricula of students training. PMID- 27393727 TI - [Not Available]. PMID- 27393728 TI - [Not Available]. PMID- 27393729 TI - Relative Added Value: What are the Tools to Evalue it? AB - The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas. First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy. PMID- 27393730 TI - [Not Available]. AB - The data on consumption of cannabis in the young people are well documented on the other hand this consumption is less described in subjects presenting a drug dependency. The consumption of cannabis in 2006 and the principal tendencies since 2004 were studied from the OPPIDUM (Observation of Illegal Drugs and Misuse of Psychotropic Medications) program's. OPPIDUM is an annual transverse national study pharmaco-epidemiologic which recruits subjects presenting a drug dependency or benefiting of a maintenance treatment. In October 2006, 3743 subjects were included. Thirty eight per cent (n = 1437) of them are consumers of cannabis, among them 27% announced consumed only cannabis and 73% consumed it with other psychoactive substances. The consumers of cannabis alone are younger, have better social-economical indicators and presented consumption of cannabis in term of abuse and dependence more important. This study underlines the problems of the polyconsommation. No change related to the characteristics of consumers of cannabis was observed between 2004 and 2006. This study underline the presence of two groups of consumers of cannabis presented in structures of care who are different on level of the social-economical indicators and its consumptions. PMID- 27393731 TI - [Sucess of the Corticosteroid Treatment during a Rare and Grave Inaugural Complication of the Lupus: the Acute Pancreatitis]. PMID- 27393732 TI - [Not Available]. PMID- 27393733 TI - Effect of antituberculosis treatment on CYP2C19 enzyme activity in genetically polymorphic South Indian Tamilian population. AB - Patients on antituberculosis therapy (ATT) are more prone to drug interactions in the presence of coexisting illnesses which require drug therapy. Rifampicin is a pleiotropic inducer of CYP enzymes, and isoniazid is an enzyme inhibitor. Genetic variations are common in the gene coding for CYP2C19 enzyme. These variations would be important in predicting the individual variations in CYP2C19 activity. The objectives of the study were to find the net effect of 1-month ATT on CYP2C19 enzyme activity and its association with CYP2C19 genetic polymorphisms. Newly diagnosed tuberculosis patients (n = 125) were included in the study. Before commencing ATT, they were given a single dose of omeprazole 20 mg as a probe drug for CYP2C19. Blood sample was collected after 3 h to carry out phenotyping for CYP2C19 enzyme by measuring omeprazole hydroxylation index (OHI) using LC-MS/MS. The phenotyping procedure was repeated after 1 month of ATT. CYP2C19 genotyping was carried out by PCR-RFLP method. Significant reduction in OHI was observed after 1 month of ATT in all the metabolizer groups. The percentage reduction in OHI was maximum with poor metabolizers, 84.1 (IQR - 74.6, 86.6), and minimum with ultra-rapid metabolizers, 39.6 (IQR - 12.7, 54.7). CYP2C19 enzyme induction is predominant in patients after 1 month of antituberculosis treatment (ATT). Genetic variations in the enzyme could not clearly explain the interindividual differences in induction. There is a potential risk of drug failure/adverse effect in poor metabolizers regardless of their genotype after ATT. PMID- 27393734 TI - The relationship between examination-related academic stress, salivary antioxidant capacity and exercise patterns of final-year Saudi dental students. AB - OBJECTIVE: To study the impact of examination stress on the total antioxidant capacity (TAC) of senior dental students and compare changes in TAC between students who exercise regularly and those who do not. METHODS: A questionnaire designed to evaluate physical activity levels, body mass index (BMI) and academic performance was distributed to 325 senior dental students. Of the 312 who responded, a total of 70 were enrolled in the study, of whom 60 completed the study. The students were composed of a low-activity group (n = 30), who had a Goddard-Sheppard (GS) exercise score of <25, and a high-exercise group (n = 30), who had a GS score >60. Dental Environment Stress (DES) questionnaires and salivary samples were collected at the first week of the semester and at the week of the examinations. Salivary TAC was measured using a commercially available Radical Absorbance Antioxidant Assay measurement kit (Zen-Bio ORACTM, AMS Biotechnology, Abington UK). A total of 60 students completed the study. RESULTS: A significant increase in DES values and a significant reduction in salivary TAC values were observed in the week of the examination compared to baseline scores. Although no differences were observed in the DES scores between the high-exercise and low-exercise groups, the high-exercise group showed a significantly lower reduction in examination week salivary TAC compared to their counterparts in the low-exercise group. Regression models showed a significant association between the TAC, exercise scores and DES scores in the week of the examinations. CONCLUSION: Regular exercise may help protect students against the oxidative stress associated with academic stress. PMID- 27393737 TI - The New Look of Behavioral Genetics in Social Inequality: Gene-Environment Interplay and Life Chances. PMID- 27393735 TI - Oral Monomethyl Fumarate Therapy Ameliorates Retinopathy in a Humanized Mouse Model of Sickle Cell Disease. AB - AIMS: Sickle retinopathy (SR) is a major cause of blindness in sickle cell disease (SCD). The genetic mutation responsible for SCD is known, however; oxidative stress and inflammation also figure prominently in the development and progression of pathology. Development of therapies for SR is hampered by the lack of (a) animal models that accurately recapitulate human SR and (b) strategies for noninvasive yet effective retinal drug delivery. This study addressed both issues by validating the Townes humanized SCD mouse as a model of SR and demonstrating the efficacy of oral administration of the antioxidant fumaric acid ester monomethyl fumarate (MMF) in the disease. RESULTS: In vivo ophthalmic imaging, electroretinography, and postmortem histological RNA and protein analyses were used to monitor retinal health and function in normal (HbAA) and sickle (HbSS) hemoglobin-producing mice over a one-year period and in additional HbAA and HbSS mice treated with MMF (15 mg/ml) for 5 months. Functional and morphological abnormalities and molecular hallmarks of oxidative stress/inflammation were evident early in HbSS retinas and increased in number and severity with age. Treatment with MMF, a known inducer of Nrf2, induced gamma-globin expression and fetal hemoglobin production, improved hematological profiles, and ameliorated SR related pathology. Innovation and Conclusion: United States Food and Drug Administration-approved formulations in which MMF is the primary bioactive ingredient are currently available to treat multiple sclerosis; such drugs may be effective for treatment of ocular and systemic complications of SCD, and given the pleiotropic effects, other nonsickle-related diseases in which oxidative stress, inflammation, and retinal vascular pathology figure prominently. Antioxid. Redox Signal. 25, 921-935. PMID- 27393736 TI - Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine or cervid prion protein. AB - Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (>=5 per homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD) or sheep with experimentally acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrPres) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100 % attack rates in Tg338, but no clinical disease at endpoint (>300 days post-inoculation, p.i.) and low attack rates (6.8 %) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrPres accumulation in Tg338 at endpoint (>500 days p.i.), but rapid onset of clinical disease (~121 days p.i.) and 100 % attack rate in TgElk. Sheep-passaged CWD resulted in transmission to both mouse lines with 100 % attack rates at endpoint in Tg338 and an attack rate of ~73 % in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats. PMID- 27393738 TI - Value in palliative cancer surgery: A critical assessment. AB - Emergency operations are associated with increased morbidity, mortality, and cost compared to elective operations. Palliative and emergent surgery for patients with advanced malignancies is associated with additional risk and remains controversial. Emergent or palliative interventions can be broadly categorized according to indication. Tumor related complications (bleeding, obstruction, or perforation) merit specific consideration, as do specific presentations such as pneumoperitoneum, pneumatosis intestinalis, or peritonitis from other causes that may arise during active therapy for malignancies. Although nonoperative, endoscopic, and interventional treatment modalities are frequently available, surgery remains the only effective therapy in selected situations such as small intestinal obstruction and tumor perforation. Selection of patients for surgery requires consideration of factors including overall prognosis, performance status, and patients' priorities. Selection and risk assessment tools underscore the limited capacity of patients' with higher risk features for durable recovery but do not supplant nuanced clinical judgment. J. Surg. Oncol. 2016;114:311-315. (c) 2016 Wiley Periodicals, Inc. PMID- 27393739 TI - The genomewide transcriptional response underlying the pea aphid wing polyphenism. AB - Phenotypic plasticity is a key life history strategy used by many plants and animals living in heterogeneous environments. A multitude of studies have investigated the costs and limits of plasticity, as well as the conditions under which it evolves. Much less well understood are the molecular genetic mechanisms that enable an organism to sense its environment and respond in a plastic manner. The pea aphid wing polyphenism is a compelling laboratory model to study these mechanisms. In this polyphenism, environmental stressors like high density cause asexual, viviparous adult female aphids to change the development of their embryos from wingless to winged morphs. The life history trade-offs between the two morphs have been intensively studied, but the molecular mechanisms underlying this process remain largely unknown. We therefore performed a genomewide study of the maternal transcriptome at two time points with and without a crowding stress to discover the maternal molecular changes that lead to the development of winged vs. wingless offspring. We observed significant transcriptional changes in genes associated with odorant binding, neurotransmitter transport, hormonal activity and chromatin remodelling in the maternal transcriptome. We also found that titres of serotonin, dopamine and octopamine were higher in solitary compared to crowded aphids. We use these results to posit a model for how maternal signals inform a developing embryo to be winged or wingless. Our findings add significant insights into the identity of the molecular mechanisms that underlie environmentally induced morph determination and suggest a possible role for biogenic amine regulation in polyphenisms generally. PMID- 27393741 TI - Quantitative assessment of organ distribution of dietary protein-bound 13 C labeled NE -carboxymethyllysine after a chronic oral exposure in mice. AB - SCOPE: NE -Carboxymethyl-lysine (CML) is a prominent advanced glycation end product which is not only found in vivo but also in food. It is known that a percentage of the dietary CML (dCML) is absorbed into the circulation and only partly excreted in the urine. Several studies have tried to measure how much dCML remains in tissues. However obstacles to interpreting the data have been found. METHODS AND RESULTS: A new protocol which discriminates dCML from native CML (nCML) has been developed. Three CML isotopes with different mass-to-charge ratios were used: nCML Nepsilon -carboxymethyl-L-lysine, dCML Nepsilon -[13 C]carboxy[13 C]methyl-L-lysine and internal standard Nepsilon -carboxymethyl-L [4,4,5,5-2 H4 ]lysine. Wild-type (n = 7) and RAGE-/- (n = 8) mice were fed for 30 days with either a control, or a BSA-bound dCML-enriched diet. Organs were analyzed for nCML and dCML using liquid chromatography-tandem mass spectrometry. Mice exposed to dCML showed an accumulation in all tissues tested except fat. The rate of deposition was high (81-320 MUgdCML /g dry matter) in kidneys, intestine, and lungs and low (<5 MUg/g) in heart, muscle, and liver. This accumulation was not RAGE dependent. CONCLUSION: The kidney is not the only organ affected by the accumulation of dCML. Its high accumulation in other tissues and organs may also, however, have important physiological consequences. PMID- 27393742 TI - Does finding early recurrence improve outcomes, and at what cost? AB - The putative goal of surveillance is the early detection of recurrence while both the cancer and patient are still treatable. To be cost and clinically effective, surveillance requires a tailored approach based on stage, tumor biology, conditional survival, and available treatment options. Although surveillance is the major component of care for cancer patients after potentially curative treatment, current guidelines for surveillance lack the high-level data seen on the treatment side of the patient care continuum. J. Surg. Oncol. 2016;114:329 335. (c) 2016 Wiley Periodicals, Inc. PMID- 27393740 TI - Development of category formation for faces differing by age in 9- to 12-month olds: An effect of experience with infant faces. AB - We examined category formation for faces differing in age in 9- and 12-month olds, and the influence of exposure to infant faces on such ability. Infants were familiarized with adult or infant faces, and then tested with a novel exemplar from the familiarized category paired with a novel exemplar from a novel category (Experiment 1). Both age groups formed discrete categories of adult and infant faces, but exposure to infant faces in everyday life did not modulate performance. The same task was conducted with child versus infant faces (Experiment 2). Whereas 9-month-olds preferred infant faces after familiarization with child faces, but not child faces after familiarization with infant faces, 12 month-olds formed discrete categories of child and infant faces. Moreover, more exposure to infant faces correlated with higher novel category preference scores when infants were familiarized with infant faces in 12-month-olds, but not 9 month-olds. The 9-month-old asymmetry did not reflect spontaneous preference for infant over child faces (Experiment 3). These findings indicate that 9- and 12 month-olds can form age-based categories of faces. The ability of 12-month-olds to form separate child and infant categories suggests that they have a more exclusive representation of face age, one that may be influenced by prior experience with infant faces. PMID- 27393743 TI - Disease Risk Analysis and Post-Release Health Surveillance for a Reintroduction Programme: the Pool Frog Pelophylax lessonae. AB - There are risks from disease in undertaking wild animal reintroduction programmes. Methods of disease risk analysis have been advocated to assess and mitigate these risks, and post-release health and disease surveillance can be used to assess the effectiveness of the disease risk analysis, but results for a reintroduction programme have not to date been recorded. We carried out a disease risk analysis for the reintroduction of pool frogs (Pelophylax lessonae) to England, using information gained from the literature and from diagnostic testing of Swedish pool frogs and native amphibians. Ranavirus and Batrachochytrium dendrobatidis were considered high-risk disease threats for pool frogs at the destination site. Quarantine was used to manage risks from disease due to these two agents at the reintroduction site: the quarantine barrier surrounded the reintroduced pool frogs. Post-release health surveillance was carried out through regular health examinations of amphibians in the field at the reintroduction site and collection and examination of dead amphibians. No significant health or disease problems were detected, but the detection rate of dead amphibians was very low. Methods to detect a higher proportion of dead reintroduced animals and closely related species are required to better assess the effects of reintroduction on health and disease. PMID- 27393745 TI - Seasonal Variation in Emergency Department Visits Among Pediatric Headache Patients. AB - OBJECTIVE: To ascertain whether seasonal variation occurs in emergency department (ED) visits for headache among children and adolescents. METHODS: A retrospective review was conducted using the electronic medical records of ED visits for headache at a tertiary children's hospital through calendar years 2010-2014. Using ICD-9 diagnostic codes for headache and migraine, the numbers of headache visits were determined and compared by season and during school months vs summer months. RESULTS: A total of 6572 headache visits occurred. Headache visits increased during the fall season (133 +/- 27 visits per month) compared with other seasons (101 +/- 19 visits per month), P <= .002, but did not differ when comparing school months (113 +/- 25 visits per month) and summer months (100 +/- 24 visits per month), P = .1. CONCLUSIONS: The corresponding increase in ED visits during the fall season coincides with the start of the school year. Academic stressors and the change in daily schedule may lead to more headaches and more ED headache visits among school-aged youth. PMID- 27393744 TI - Implementing Algorithm-Guided Warfarin Dosing in an Ethnically Diverse Patient Population Using Electronic Health Records and Preemptive CYP2C9 and VKORC1 Genetic Testing. AB - Implementation of pharmacogenetic-guided warfarin dosing has been hindered by inconsistent results from reported clinical trials and a lack of available algorithms that include alleles prevalent in non-white populations. However, current evidence indicates that algorithm-guided dosing is more accurate than empirical dosing. To facilitate multiethnic algorithm-guided warfarin dosing using preemptive genetic testing, we developed a strategy that accounts for the complexity of race and leverages electronic health records for algorithm variables and deploying point-of-care dose recommendations. PMID- 27393746 TI - Gambling and violence in a nationally representative sample of UK men. AB - BACKGROUND AND AIMS: The relationship between violence and problem gambling in general population samples is under-researched and requires further attention to inform treatment and prevention efforts. We investigated the relationship between gambling problems and violence among men and sought to determine if the link can be accounted for by mental disorders, alcohol and drug dependence and impulsivity. DESIGN: A cross-sectional survey. SETTING: A UK representative general population survey conducted in 2009. PARTICIPANTS: A total of 3025 UK men aged 18-64 years. MEASUREMENTS: Binary logistic regression was used to examine relationships. Outcome measures included gambling behaviour and self-reports of violence. Covariates included alcohol and drug dependence, mental illness, impulsivity and socio-demography. FINDINGS: Problem gambling and probable pathological gambling were associated with increased odds of the perpetration of violence [adjusted odd ratios (AOR) = 3.09, confidence interval (CI) = 1.90-5.00 and 4.09, CI = 2.76-6.30, respectively] and a range of other behaviours, such as using a weapon (AORs = 4.93, CI = 2.52-9.63 and 6.33, CI = 3.52-11.38) and the perpetration of intimate partner violence (AOR = 9.80, CI =2.45-39.04). The results were attenuated when adjusted for comorbid mental illness and impulsivity, but remained statistically significant. Alcohol and drug dependence had the most impact; relationships were most attenuated when they added into the models, with the latter having the largest effect. CONCLUSIONS: Among men in the United Kingdom, self-reports of problem/pathological gambling remain predictive of a range of measures of violent behaviour after adjusting for alcohol and drug dependence, comorbid mental disorder and impulsivity; of the covariates, alcohol and drug dependence have the greatest effect in attenuating the gambling-violence association. PMID- 27393747 TI - Wait time to seek skin cancer screening in Italy. PMID- 27393749 TI - A Traumatic Epidural Hematoma in a 15-Year-Old Male. PMID- 27393750 TI - The Sepsis Saga: Consensus to Xigris. PMID- 27393751 TI - Two Girls Falsely Imprisoned After Mother Killed. PMID- 27393754 TI - 2016 Air Medical Transport Conference-Queen City, Here We Come! PMID- 27393755 TI - Understanding Hypoxic Drive and the Release of Hypoxic Vasoconstriction. AB - Understanding the hypoxic drive and release of hypoxic vasoconstriction in the chronic obstructive pulmonary disease population can be somewhat confusing and misunderstood. Furthermore, the hypoxic drive theory is one in which there really is no scientific evidence to support and yet continues to prosper in every aspect of care in regard to the chronic lung patient, from prehospital all the way to intensive care unit and home care therapy. This subject review will hopefully enhance some understanding of what exactly goes on with these patients and the importance of providing oxygen when it is desperately needed. PMID- 27393756 TI - Challenges and Resources for New Critical Care Transport Crewmembers: A Descriptive Exploratory Study. AB - OBJECTIVE: The purpose of this study was to identify the challenges new crewmembers experience in the critical care transport (CCT) environment and to determine the most valuable resources when acclimating to the transport environment. To date, no study has focused on the unique challenges nor the resources most effective in CCT training. METHODS: This descriptive exploratory study was conducted with a convenience survey sent to the 3 largest professional CCT organizations: the Association of Air Medical Services, the Air and Surface Transport Nurses Association, and the Association of Critical Care Transport. RESULTS: The study survey responses revealed that more education and training are needed. Novice crewmembers identified areas in safety, communication, environment, and crew resource management as particularly challenging. Responses also validate the need for more simulation training, especially for CCT of low volume/high-risk patient populations. CONCLUSION: Results of this survey provide valuable insight for improving training effectiveness of health care professionals transitioning to the CCT environment. More information regarding best practice on the frequency and timing of CCT simulation training should be collected, particularly for simulations completed in the transport environment. PMID- 27393757 TI - Air Medical Evacuations From the German North Sea Wind Farm Bard Offshore 1: Traumatic Injuries, Acute Diseases, and Rescue Process Times (2011-2013). AB - OBJECTIVE: Our purpose was 2-fold: 1) to show emergency-related traumatic injury and acute disease patterns and 2) to evaluate air rescue process times in a remotely located German offshore wind farm. Optimally, this will support methodologies to reduce offshore help time (time from the incoming emergency call until offshore arrival of the helicopter). METHODS: The type and severity of traumatic injuries and acute diseases were retrospectively analyzed for 39 air medevacs from August 2011 to December 2013, and the process times of air rescue missions were evaluated in detail. RESULTS: Forty-nine percent of the medevacs were related to traumatic injuries, whereas 41% were associated with acute diseases and 10% remained unclear. Cardiovascular and gastrointestinal disorders accounted for 90% of internal medical cases. About 69% of the trauma was related to contusions, lacerations, and cuts. The main body regions injured were limbs (~59%) and head (~32%). The total rescue time until arrival at the destination facility averaged 175.3 minutes (standard deviation = 54.4 minutes). The mean helicopter offshore arrival time was 106.9 minutes (standard deviation = 57.4 minutes) after the incoming emergency call. In 64% of the medevacs, the helicopter arrived on scene within a help time of 90 minutes. CONCLUSION: A reduction of help time (<= 60 minutes) for time-critical severe trauma and acute diseases may be anticipated through rapid and focused medical and logistic decision-making processes by the onshore dispatch center combined with professional, qualified, and well-trained flight and rescue personnel. PMID- 27393758 TI - Safety and Efficacy of Thoracostomy in the Air Medical Environment. AB - OBJECTIVE: The use of thoracostomy to treat tension pneumothorax is a core skill for prehospital providers. Tension pneumothoraces are potentially lethal and are often encountered in the prehospital environment. METHODS: The authors reviewed the prehospital electronic medical records of patients who had undergone finger thoracostomy (FT) or tube thoracostomy (TT) while under the care of air medical crewmembers. Demographic data were obtained along with survival and complications. RESULTS: During the 90-month data period, 250 patients (18 years of age or older) underwent FT/TT, with a total of 421 procedures performed. The mean age of patients was 44.8 years, with 78.4% being male and 21.6% being female; 98.4% of patients had traumatic injuries. Cardiopulmonary resuscitation was required in 65.2% of patients undergoing FT/TT; 34.8% did not require cardiopulmonary resuscitation. Thirty percent of patients exhibited clinical improvement such as increasing systolic blood pressure, oxygen saturation, improved lung compliance, or a release of blood or air under tension. Patients who experienced complications such as tube dislodgement or empyema made up 3.4% of the cohort. CONCLUSION: The results of this study suggest that flight crews can use FT/TT in their practice on patients with actual or potential pneumothoraces with limited complications and generate clinical improvement in a subset of patients. PMID- 27393759 TI - Intra-aortic Balloon Pump-Dependent Patient Transports by Critical Care Paramedics. AB - OBJECTIVE: Transport of intra-aortic balloon pump (IABP)-dependent patients between hospitals is increasingly common. The transports are typically time sensitive and require personnel familiar with IABP operation and management of a potentially unstable patient. This study examined transports performed by specially trained critical care paramedics in a large air medical and land critical care transport service. METHODS: This retrospective, descriptive review prospectively collected data for IABP-dependent patient transports in Ontario, Canada in a 10-year interval beginning September 2003. Call records and patient care reports were reviewed to capture demographic, patient care, adverse events, and transport-related data. Adverse events, including resuscitation medication, procedure, and patient instability, were independently reviewed by 2 investigators. RESULTS: There were 162 IABP-dependent patients transported. Seventy-one were performed by land critical care transport vehicles, 60 by helicopter, and 31 by fixed wing aircraft. The mean patient age was 63.7 +/- 13.8 years; the majority (72.2%) were men. Fifty-nine patients (36.4%) were inotrope or vasopressor dependent, and 46 (28.4%) were intubated and mechanically ventilated. The most common indications for IABP insertion were acute myocardial infarction requiring prompt surgical intervention (n = 70), bridge to definitive care (n = 41), and cardiogenic shock (n = 37). The mean transport time was 92.7 +/- 79.4 minutes. There were 48 adverse events in 35 patients, most commonly hypotension (systolic blood pressure < 90 mm Hg, n = 18) and tachyarrhythmia requiring therapy (n = 12). There were 3 IABP-related events and 3 cases in which the transport vehicle was inoperable resulting in a transport delay. One patient with cardiogenic shock died before departing the sending hospital. Paramedics managed all events without assistance from other health care personnel. CONCLUSION: Specially trained critical care flight paramedics can safely transport potentially unstable IABP-dependent patients to definitive cardiac surgical care. PMID- 27393760 TI - Management of Septic Shock in the Remote Prehospital Setting. AB - This study aims to assess the management of septic shock by air medical retrieval teams in the remote setting. A retrospective observational study was performed over 36 months. Sixty-seven adult patients who met the criteria for septic shock were included. Respiratory sepsis was the working diagnosis for 53% of patients; this was confirmed on intensive care unit (ICU) discharge in 39% of patients. Intravenous antibiotics and oxygen were delivered in over 90% of patients. Central and arterial line insertions were performed in 48% and 40% of patients, respectively, and 79% of patients were catheterized. Thirty-three percent of patients required intubation, and 80% of patients received an initial crystalloid fluid bolus of 20 mL/kg. Vasopressors were started in 89% of patients. Upon reaching definitive care, 91% of patients were admitted to a high-dependency or ICU setting, with a median length of ICU stay of 4 days and a 30-day mortality of 13%. Of those admitted to the ICU, intubation was required in 48%, new renal support in 20%, and blood pressure support in 84% of patients, respectively. Septic shock was recognized early and managed aggressively by remote retrieval teams, which may have contributed to the low mortality rate observed. PMID- 27393761 TI - Limb Replantation in Air-Transported Patients: A 4-Year Study. AB - OBJECTIVE: Patients who require extremity reimplantation represent a population in whom rapid transport could provide potential benefit. Only 1 previous report has described the use of air transport in patients with these injuries. We describe our experience in air medical transport of limb reimplantation candidates. METHODS: A retrospective chart review for all patients with amputation or near-amputation extremity injuries who were transported by helicopter to a regional reimplantation center over a 4-year period was conducted. The primary outcome measure was patients who were taken to the operating room (OR) for a definitive repair attempt by the surgical team. RESULTS: Of the 115 patients, 104 were taken to the OR (90%), and 84 (80%) had a repair attempted. Similar results were found between those patients who were transported from the scene or another hospital with regard to the number of candidates taken to the OR and the number of patients in who definitive repair was attempted. CONCLUSION: Air medical transport can play an important role in a regional reimplantation program. PMID- 27393762 TI - Simulator-Based Air Medical Training Program Christoph Life: From Concept to Course. AB - OBJECTIVE: Christoph Life is a simulator-based air medical training program and a new and innovative educational concept. Participants pass different scenarios with a fully equipped and movable helicopter simulator. Main focuses of the program are crew resource management (CRM) elements and team training. Information about expectations end effectiveness of the training is sparse. METHODS: During a 2-day training, participants learn CRM basics and complete various emergency medical scenarios. For evaluation, we used an anonymous questionnaire either with polar questions or a 6-coded psychometric Likert scale. The Wilcoxon test was used for statistical analysis. The significance level was set at P < .05. RESULTS: Thirteen teams of emergency physicians and specially trained paramedics underwent Christoph Life. It was evaluated largely positively and considered very helpful for daily work (5.7 +/- 0.5) and avoiding mistakes (5.7 +/- 0.5). The quality of participants' knowledge about CRM basics (3.5 +/- 1.2 vs. 5.4 +/- 0.7, P < .001), self-assessment of communication skills (4.2 +/- 0.7 vs. 4.8 +/- 0.8, P = .02), and active reflection of communication aspects (3.9 +/- 0.9 vs. 5.5 +/- 0.5, P < .001) could be strikingly increased. CONCLUSIONS: There is a considerable demand for intensified training on the part of the users. We were able to show that a simulator-based air medical training program is a helpful training tool with an obvious subjective benefit for the participants' nontechnical skills. PMID- 27393763 TI - Stability of Drugs Used in Helicopter Air Medical Emergency Services: An Exploratory Study. AB - OBJECTIVE: Transportation by air exposes drugs used in emergency medical services to vibrations. The aim of the study was to determine whether or not vibrations caused by a helicopter induce the degradation of 5 drugs used in this setting. METHODS: A longitudinal study in an operating medical helicopter along with a worst case was conducted. The studied drugs were 3 drugs labeled for refrigeration (cisatracurium, lorazepam, and succinylcholine) and 2 albumin solutions (human albumin 4% and 20%). These drugs were stored for 4 months according to the following conditions: inside a helicopter, worst case with exposure to extreme vibrations, at room temperature, and according to manufacturers' recommendations. Samples were analyzed with validated high performance liquid chromatography assay methods. A drug was considered stable if the remaining drug content was above 90% of the label claim. Except for the albumin solutions, visual inspection was used to determine instability by the formation of aggregates. RESULTS: Only the samples stored at room temperature became unstable after 4 months. No difference in extreme foaming was observed in the albumin solutions. CONCLUSIONS: These data suggest that the effect of degradation of drugs caused by vibrations is negligible. Temperature was observed as the main cause of drug degradation. PMID- 27393765 TI - Concern Network. PMID- 27393764 TI - Flying the Unfriendly Skies: A Case Report. AB - We report the case of an older adult foreign national with severe respiratory failure who was brought via a commercial airline to the United States. Hospitalized and orally intubated in his home country, his son, a US citizen, decided to translocate his father to the United States. He purchased tickets for adjoining seats on a prominent international commercial airline and brought his orally intubated, stretcher-bound father onto the plane without any accompanying medical professionals, security screening, or preapproved transport. Despite this, they traveled to New York and phoned 911 upon landing, allowing him to bypass the standard customs procedures. PMID- 27393766 TI - Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach. AB - Primary biliary cholangitis (PBC; previously "primary biliary cirrhosis") is a cholestatic, putatively autoimmune-mediated liver disease with a clear female preponderance affecting the intrahepatic small and medium-size bile ducts and resulting in bile duct destruction, ductopenia and portal fibrosis that progresses slowly to biliary cirrhosis. Despite suboptimal response in one third of patients treated with ursodeoxycholic acid (UDCA), this remains the only FDA approved agent for this disease. In this review, we cover recent advances in research that have yielded numerous agents currently at different stages of the drug pipeline, some of which are expected to be approved in the near future. We also discuss accumulating evidence supporting the use of older agents (fibrates and glucocorticoids) as an adjunctive therapy to UDCA in non-responsive patients. We suggest that with the imminent expansion of the therapeutic armamentarium for PBC, a more comprehensive approach - ideally taking into account not only biochemical markers of disease stage - is needed to better select patients in whom these strategies might be most useful. Studies are also needed to compare the relative efficacy of different proposed second-line treatments not only against UDCA monotherapy. PMID- 27393767 TI - A method for easily customizable gradient gel electrophoresis. AB - Gradient polyacrylamide gel electrophoresis is a powerful tool for the resolution of polypeptides by relative mobility. Here, we present a simplified method for generating polyacrylamide gradient gels for routine analysis without the need for specialized mixing equipment. The method allows for easily customizable gradients which can be optimized for specific polypeptide resolution requirements. Moreover, the method eliminates the possibility of buffer cross contamination in mixing equipment, and the time and resources saved with this method in place of traditional gradient mixing, or the purchase of pre-cast gels, are noteworthy given the frequency with which many labs use gradient gel SDS-PAGE. PMID- 27393768 TI - Editorial: Promising approaches to identify DILI drugs. PMID- 27393769 TI - Molecular epidemiology of coagulase-negative bloodstream isolates: detection of Staphylococcus epidermidis ST2, ST7 and linezolid-resistant ST23. AB - The mechanisms contributing to persistence of coagulase-negative staphylococci are diverse; to better understanding of their dynamics, the characterization of nosocomial isolates is needed. Our aim was to characterize phenotypic and molecular characteristics of Staphylococcus epidermidis and Staphylococcus haemolyticus human blood isolates from two tertiary care hospitals in Mexico, the Hospital Universitario in Monterrey and the Hospital Civil in Guadalajara. Antimicrobial susceptibility was determined. Biofilm formation was assessed by crystal violet staining. Detection of the ica operon and Staphylococcal Cassette Chromosome mec typing were performed by PCR. Clonal relatedness was determined by Pulsed-fiel gel electrophoresis and Multi locus sequence typing. Methicillin resistance was 85.5% and 93.2% for S. epidermidis and S. haemolyticus, respectively. Both species showed resistance >70% to norfloxacin, clindamycin, levofloxacin, trimethoprim/sulfamethoxazole, and erythromycin. Three S. epidermidis and two S. haemolyticus isolates were linezolid-resistant (one isolate of each species was cfr+). Most isolates of both species were strong biofilm producers (92.8% of S. epidermidis and 72.9% of S. haemolyticus). The ica operon was amplified in 36 (43.4%) S. epidermidis isolates. SCCmec type IV was found in 47.2% of the S. epidermidis isolates and SCCmec type V in 14.5% of S. haemolyticus isolates. No clonal relatedness was found in either species. Resistance to clindamycin, levofloxacin, erythromycin, oxacillin, and cefoxitin was associated with biofilm production for both species (p<0.05). A G2576T mutation in 23S rRNA gene was detected in an S. haemolyticus linezolid-resistant isolate. All linezolid-resistant S. epidermidis isolates belonged to ST23; isolate with SCCmec type IV belonged to ST7, and isolate with SCCmec type III belonged to ST2. This is the first report of ST7 in Mexico. There was a high genetic diversity in both species, though both species shared characteristics that may contibute to virulence. PMID- 27393770 TI - Chronic Rhinosinusitis with Nasal Polyps. AB - Chronic rhinosinusitis with nasal polyps (CRSwNP) is an important clinical entity diagnosed by the presence of both subjective and objective evidence of chronic sinonasal inflammation. Symptoms include anterior or posterior rhinorrhea, nasal congestion, hyposmia, and/or facial pressure or pain that last for a duration of more than 12 weeks. Nasal polyps are inflammatory lesions that project into the nasal airway, are typically bilateral, and originate from the ethmoid sinus. Males are more likely to be affected than females, but no specific genetic or environmental factors have been strongly linked to the development of this disorder to date. CRSwNP is frequently associated with asthma and allergic rhinitis, but the cellular and molecular mechanisms that contribute to the clinical symptoms are not fully understood. Defects in the sinonasal epithelial cell barrier, increased exposure to pathogenic and colonized bacteria, and dysregulation of the host immune system are all thought to play prominent roles in disease pathogenesis. Additional studies are needed to further explore the clinical and pathophysiological features of CRSwNP so that biomarkers can be identified and novel advances can be made to improve the treatment and management of this disease. PMID- 27393773 TI - Aspirin or Nonsteroidal Anti-inflammatory Drug-Exacerbated Chronic Rhinosinusitis. AB - Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by upper airway congestion due to eosinophilic inflammation of the nasal and sinus membranes and nasal polyposis, associated with increased leukotriene production that is further accentuated by ASA or other nonsteroidal anti-inflammatory drug (NSAID) ingestion. It occurs in 5% to 10% of subjects with chronic rhinosinusitis (CRS) and in 15% to 40% of those with nasal polyposis. Although AERD with CRS is usually associated with asthma, this is not always the case. The eosinophilic airway inflammation and symptoms precede clinical reactions to ASA or other NSAIDs, but ultimately affected subjects experience worsening of symptoms with ingestion of ASA/NSAIDs. The endotypic mechanism for this worsening is related to a chronic increase in leukotriene and a decrease in prostaglandin production, particularly prostaglandin E2, that is further aggravated by the inhibition of cycloxgenase I. IgE does not likely play a role in the pathogenesis of the disease although nasal and sinus staphylococcal infection increases local IgE level and may increase total IgE and specific IgE levels. Genetic studies suggest that multiple genes may be involved, but the genetic abnormalities may differ in affected subjects from different ethnicities and candidate genes have not been confirmed in multiple studies. Genome-wide association studies have not been revealing. The phenotype is recognized by the mucosal inflammation and worsening of symptoms acutely with ASA/NSAID. There is clinical improvement with ASA desensitization followed by regular ingestion of ASA or other NSAIDs. Further understanding of this unique phenotype and endotype of CRS will likely improve the understanding of other eosinophilic airway diseases. PMID- 27393772 TI - Infectious Chronic Rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a persistent inflammatory disease that affects a multitude of people worldwide. The pathogenesis of CRS involves many factors including genetics, status of the sinonasal microbiome, infections, and environmental influences. Comorbidities associated with CRS include asthma, allergic rhinitis, bronchiectasis, and certain kinds of immunodeficiency. CRS can be divided into different subtypes based on endotypes and phenotypes. Infectious CRS is one such category. The etiology of infectious CRS is usually secondary to chronic bacterial infection that commonly begins with a viral upper respiratory tract infection. Humoral antibody deficiencies can underlie difficult-to-treat or recurrent CRS. Infectious CRS can be treated with antimicrobials, topical or oral corticosteroids, and nasal saline irrigations. Patients with CRS and humoral immunodeficiency may require an aggressive treatment approach including immunoglobulin replacement therapy. Despite advancements in the field of CRS, targeted therapies and reliable biomarkers are still lacking. PMID- 27393771 TI - Chronic Rhinosinusitis without Nasal Polyps. AB - Chronic rhinosinusitis without nasal polyps (CRSsNP) is more prevalent than chronic rhinosinusitis with nasal polyps (CRSwNP). Certain diseases predispose to whereas others are associated with CRSsNP. Predisposing diseases include allergic and nonallergic upper and lower airway diseases, epithelial cell disorders, immunodeficiencies, autoimmune diseases, and some infectious diseases. In addition, environmental and host factors, examples of which include smoking, a higher incidence of abnormal biofilms, and innate immune defects, play a role in the pathogenesis of this disease. CRSsNP is characterized by histologic abnormalities, including basement membrane thickening (fibrosis) and goblet cell hyperplasia. Neutrophils and several chemokines, TGF-beta and C-X-C motif chemokine ligand (CXCL)-8, play a role in CRSsNP remodeling. However, there are conflicting data about CRSsNP endotypes, for example, whether it is characterized by neutrophilia or eosinophilia or both. In spite of advancements and the understanding of the pathogenesis of this disease, additional study is necessary to better comprehend its underlying mechanisms, endotypes, and evidence-based treatment strategies. PMID- 27393774 TI - Allergic Fungal Rhinosinusitis. AB - This article reviews the history of allergic fungal rhinosinusitis and the clinical, pathologic, and radiographic criteria necessary to establish its diagnosis and differentiate this disease from other types of chronic rhinosinusitis. Allergic fungal rhinosinusitis is a noninvasive fungal form of sinus inflammation characterized by an often times unilateral, expansile process in which the typical allergic "peanut-butter-like" mucin contributes to the formation of nasal polyps, hyposmia/anosmia, and structural changes of the face. IgE sensitization to fungi is a necessary, but not sufficient, pathophysiologic component of the disease process that is also defined by microscopic visualization of mucin-containing fungus and characteristic radiological imaging. This article expounds on these details and others including the key clinical and scientific distinctions of this diagnosis, the pathophysiologic mechanisms beyond IgE-mediated hypersensitivity that must be at play, and areas of current and future research. PMID- 27393775 TI - Chronic Rhinosinusitis in Patients with Cystic Fibrosis. AB - Chronic rhinosinusitis (CRS) is highly prevalent in patients with cystic fibrosis (CF) and accounts for significant morbidity and contribution to CF lung disease. Mutations of the cystic fibrosis transmembrane regulator gene occur with increased prevalence in patients with CRS without CF, suggesting some contribution to CRS pathophysiology. Nasal polyps (NPs) occur with increased prevalence in patients with CF of all ages and have a more neutrophilic appearance with fewer eosinophils and increased submucosal glandular elements in comparison to NPs from patients without CF. Mainstays of medical treatment include isotonic saline irrigations and topical intranasal glucocorticoids, with some evidence that topical intranasal glucocorticoids reduce NP size. Although inhaled hypertonic saline (7%) has been widely studied as a mucolytic agent for CF lung disease, there are no reports of its use in CF CRS. Mucolytics have also not been studied as a treatment for CRS in CF, and most evidence does not support their use for CF lung disease. Nasally nebulized dornase alfa (recombinant human deoxyribonuclease) following sinus surgery shows promise for treatment. Other unproven therapies include addition of baby shampoo to isotonic saline to potentially thin mucus and help prevent biofilm formation. There are no data to support the use of low-dose oral macrolide antibiotics or the use of prophylactic oral antibiotics for CRS in patients with CF. However, there is some support for the use of topical antibiotics, including colistimethate sodium or tobramycin, administered as a sinus irrigation or antral lavage in patients following sinus surgery when susceptible bacteria are cultured. Key components of CF sinus surgical management include extensive surgery to ensure that the maxillary, frontal, sphenoid, and ethmoid sinuses are all widely opened with smoothing of bony overhangs to prevent mucus retention and bacterial recolonization, postoperative meticulous daily nasal irrigations, and appropriate use of culture directed topical antibiotics. There are no data yet on whether CF-targeted therapies, including ivacaftor or ivacaftor combined with lumacaftor, have an impact on CF CRS. PMID- 27393776 TI - Other Phenotypes and Treatment of Chronic Rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is difficult to define, partly because the disease recognized by clinicians is both heterogeneous and the endpoint of different pathophysiologic, genetic, and environmental interactions. For this article, we define CRS as symptoms lasting more than 3 months combined with an imaging study showing inflammation in the sinuses. This article comments on some factors that are believed to influence the expression of CRS. These factors include anatomic abnormalities, immotile cilia, age, allergic sensitization, immune deficiency, dental infections, gastrointestinal reflux, smoking, biofilm, and the microbiome. Other factors are discussed in other sections. The article concludes with an overview of treatment. In brief, nasal steroids and large volume nasal irrigations are the first line of treatment for this inflammatory disease. Antibiotics are used when infections are thought to contribute. Oral steroids are frequently used in severe disease. Endoscopy and sinus computed tomography scans are used when surgery is contemplated. PMID- 27393777 TI - Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. AB - Chronic rhinosinusitis can be differentiated into several phenotypes based on clinical criteria; however, these phenotypes do not teach us much about the underlying inflammatory mechanisms. Thus, the use of nasal endoscopy and CT scanning, and eventually taking a swab or a biopsy, may not be sufficient to fully appreciate the individual patient's pathology. Endotyping of chronic rhinosinusitis on the basis of pathomechanisms, functionally and pathologically different from others by the involvement of specific molecules or cells, may in contrast provide us with information on the risk of disease progression or recurrence and on the best available treatment, and also helps us identifying innovative therapeutic targets for treatment. Endotyping may best be structured around T helper cells and their downstream events, such as tissue eosinophilia or neutrophilia; this approach involves the cytokines and chemokines related to specific T helper cell populations, and related markers such as IgE. Endotyping is of specific interest at the time of the arrival of new biologicals, confronting us with the challenge of the selection of eligible patients for treatment and predicting their therapeutic response; defining suitable biomarkers is therefore an urgent task. Failure to appreciate the underlying mechanisms and endotypes of chronic rhinosinusitis may limit progress in the management of the disease at present. PMID- 27393778 TI - Chronic Rhinosinusitis Phenotypes: An Approach to Better Medical Care for Chronic Rhinosinusitis. PMID- 27393779 TI - Can We Clear the Air? PMID- 27393780 TI - The Minimally Clinically Important Difference (MCID): What Difference Does It Make? PMID- 27393781 TI - Is the Prevalence of Food Allergy Not on the Rise After All? PMID- 27393782 TI - The Promise of Improving Asthma Control Using Mobile Health. PMID- 27393783 TI - Immune-Mediated and Adverse Drug Reactions During Treatment with the Fifth Generation Cephalosporin, Ceftaroline: Drug Allergy Matters. PMID- 27393784 TI - Aspirin-exacerbated respiratory disease: not always "adult-onset". PMID- 27393786 TI - Occupational Asthma. PMID- 27393785 TI - First fatalities from tick bite anaphylaxis. PMID- 27393787 TI - Hypogammaglobulinemia without Infection. PMID- 27393788 TI - Can an increased cholinergic tone constitute a predictor of positive response to tiotropium in patients with moderate asthma? PMID- 27393789 TI - Safe and Time-Saving Desensitization Protocol to Intravenous Etoposide. PMID- 27393790 TI - Reply. PMID- 27393791 TI - Reply. PMID- 27393792 TI - Erratum to "Laryngeal metastases of acral lentiginous melanoma: Narrow band imaging". PMID- 27393793 TI - Extremely High Expression of Antisense RNA for Wilms' Tumor 1 in Active Osteoclasts: Suppression of Wilms' Tumor 1 Protein Expression during Osteoclastogenesis. AB - Wilms' tumor 1 (WT1), a zinc-finger transcription regulator of the early growth response family, identified as the product of a tumor suppressor gene of Wilms' tumors, bears potential ability to induce macrophage differentiation in blood cell differentiation. Herein, we examined the involvement of WT1 in the regulation of osteoclastogenesis. We detected a high level of WT1 protein expression in osteoclast precursors; however, WT1 expression was markedly suppressed during osteoclastogenesis. We examined expression of WT1 transcripts in bone tissue by RNA in situ hybridization. We found a high level of antisense transcripts in osteoclasts actively resorbing bone in mandible of newborn rats. Expression of antisense WT1 RNA in mandible was also confirmed by Northern blot analysis and strand-specific RT-PCR. Overexpression of antisense WT1 RNA in RAW-D cells, an osteoclast precursor cell line, resulted in a marked enhancement of osteoclastogenesis, suggesting that antisense WT1 RNA functions to suppress expression of WT1 protein in osteoclastogenesis. High level expression of antisense WT1 RNA may contribute to commitment to osteoclastogenesis, and may allow osteoclasts to maintain or stabilize their differentiation state. PMID- 27393794 TI - Clinical calculators in hospital medicine: Availability, classification, and needs. AB - OBJECTIVE: Clinical calculators are widely used in modern clinical practice, but are not generally applied to electronic health record (EHR) systems. Important barriers to the application of these clinical calculators into existing EHR systems include the need for real-time calculation, human-calculator interaction, and data source requirements. The objective of this study was to identify, classify, and evaluate the use of available clinical calculators for clinicians in the hospital setting. METHODS: Dedicated online resources with medical calculators and providers of aggregated medical information were queried for readily available clinical calculators. Calculators were mapped by clinical categories, mechanism of calculation, and the goal of calculation. Online statistics from selected Internet resources and clinician opinion were used to assess the use of clinical calculators. RESULTS: One hundred seventy-six readily available calculators in 4 categories, 6 primary specialties, and 40 subspecialties were identified. The goals of calculation included prediction, severity, risk estimation, diagnostic, and decision-making aid. A combination of summation logic with cutoffs or rules was the most frequent mechanism of computation. Combined results, online resources, statistics, and clinician opinion identified 13 most utilized calculators. CONCLUSION: Although not an exhaustive list, a total of 176 validated calculators were identified, classified, and evaluated for usefulness. Most of these calculators are used for adult patients in the critical care or internal medicine settings. Thirteen of 176 clinical calculators were determined to be useful in our institution. All of these calculators have an interface for manual input. PMID- 27393795 TI - A novel encoding Lempel-Ziv complexity algorithm for quantifying the irregularity of physiological time series. AB - BACKGROUND AND OBJECTIVE: The Lempel-Ziv (LZ) complexity and its variants have been extensively used to analyze the irregularity of physiological time series. To date, these measures cannot explicitly discern between the irregularity and the chaotic characteristics of physiological time series. Our study compared the performance of an encoding LZ (ELZ) complexity algorithm, a novel variant of the LZ complexity algorithm, with those of the classic LZ (CLZ) and multistate LZ (MLZ) complexity algorithms. METHODS AND RESULTS: Simulation experiments on Gaussian noise, logistic chaotic, and periodic time series showed that only the ELZ algorithm monotonically declined with the reduction in irregularity in time series, whereas the CLZ and MLZ approaches yielded overlapped values for chaotic time series and time series mixed with Gaussian noise, demonstrating the accuracy of the proposed ELZ algorithm in capturing the irregularity, rather than the complexity, of physiological time series. In addition, the effect of sequence length on the ELZ algorithm was more stable compared with those on CLZ and MLZ, especially when the sequence length was longer than 300. A sensitivity analysis for all three LZ algorithms revealed that both the MLZ and the ELZ algorithms could respond to the change in time sequences, whereas the CLZ approach could not. Cardiac interbeat (RR) interval time series from the MIT-BIH database were also evaluated, and the results showed that the ELZ algorithm could accurately measure the inherent irregularity of the RR interval time series, as indicated by lower LZ values yielded from a congestive heart failure group versus those yielded from a normal sinus rhythm group (p < 0.01). PMID- 27393796 TI - The effect of an integrated education model on anxiety and uncertainty in patients undergoing cervical disc herniation surgery. AB - BACKGROUND: Educating patients about receiving surgical procedures is becoming an important issue, as it can reduce anxiety and uncertainty while helping to hasten decisions for undergoing time sensitive surgeries. We evaluated a new integrated education model for patients undergoing cervical disc herniation surgery using a quasi-experimental design. METHODS: The participants were grouped into either the new integrated educational model (n = 32) or the standard group (n = 32) on the basis of their ward numbers assigned at admission. Anxiety, uncertainty, and patient satisfaction were measured before (pre-test) and after the educational intervention (post-test-1) and post-surgery (post-test-2) to assess the effectiveness of the model in this intervention. RESULTS: We found that the generalized estimating equation modeling demonstrated this new integrated education model was more effective than the conventional model in reducing patients' anxiety and uncertainty (p <0.05). Patients were also more satisfied with our newly developed model as it takes a more holistic approach to individual health. CONCLUSION: This novel systemic educational model enhances patient's understanding of the medical condition and surgery while promoting patient caregiver interaction for optimal patient health outcomes. We present a comprehensive and consistent platform for educational purposes in patients undergoing surgery as well as reducing the psychological burden from anxiety and uncertainty. Integrating medicine, nursing, and new technologies into an e practice and e-learning platform offers the potential of easier understanding and usage. It could revolutionize patient education in the future. PMID- 27393797 TI - A fast 3D adaptive bilateral filter for ultrasound volume visualization. AB - BACKGROUND AND OBJECTIVE: This paper introduces an effective noise removal method for medical ultrasound volume data. Ultrasound data usually need to be filtered because they contain significant noise. Conventional two-dimensional (2D) filtering methods cannot use the implicit information between adjacent layers, and existing 3D filtering methods are slow because of complicated filter kernels. Even though one filter method utilizes simple filters for speed, it is inefficient at removing noise and does not take into account the characteristics of ultrasound sampling. To solve this problem, we introduce a fast filtering method using parallel bilateral filtering and adjust the filter window size proportionally according to its position. METHODS: We devised a parallel bilateral filtering by obtaining a 3D summed area table of a quantized spatial filter. The filtering method is made adaptive by changing the kernel window size according to the distance from the ultrasound signal transmission point. RESULTS: Experiments were performed to compare the noise removal and loss of original data of the anisotropic diffusion filtering, bilateral filtering, and adaptive bilateral filtering of ultrasound volume-rendered images. The results show that the adaptive filter correctly takes into account the sampling characteristics of the ultrasound volumes. CONCLUSIONS: The proposed method can more efficiently remove noise and minimize distortion from ultrasound data than existing simple or non-adaptive filtering methods. PMID- 27393798 TI - Extraction of sulcal medial surface and classification of Alzheimer's disease using sulcal features. AB - BACKGROUND: Recent advancements in medical imaging have resulted in a significant growth in diagnostic possibilities of neurodegenerative disorders. Neuroanatomical abnormalities of the cerebral cortex in Alzheimer's disease (AD), the most frequent type of dementia in the elderly, can be observed in morphology analysis of cortical sulci, and used to distinguish between cognitively normal (CN) subjects and subjects with AD. OBJECTIVE: The purpose of this paper was to extract sulcal features by means of computing a sulcal medial surface for AD/CN classification. METHODS: 24 distinct sulci per subject were extracted from 210 subjects from the ADNI database by the BrainVISA sulcal identification pipeline. Sulcal medial surface features (depth, length, mean and Gaussian curvature, surface area) were computed for AD/CN classification with a support vector machine (SVM). RESULTS: The obtained 10-fold cross-validated classification accuracy was 87.9%, sensitivity 90.0%, and specificity 86.7%, based on ten features. The area under the receiver operating characteristic curve (AUC) was 0.89. CONCLUSIONS: The sulcal medial surface features can be used as biomarkers for cortical neuroanatomical abnormalities in AD. All the features were located in the left hemisphere, which had previously been reported to be more severely affected in AD and to lose grey matter faster than the right hemisphere. PMID- 27393799 TI - Using meta-differential evolution to enhance a calculation of a continuous blood glucose level. AB - We developed a new model of glucose dynamics. The model calculates blood glucose level as a function of transcapillary glucose transport. In previous studies, we validated the model with animal experiments. We used analytical method to determine model parameters. In this study, we validate the model with subjects with type 1 diabetes. In addition, we combine the analytic method with meta differential evolution. To validate the model with human patients, we obtained a data set of type 1 diabetes study that was coordinated by Jaeb Center for Health Research. We calculated a continuous blood glucose level from continuously measured interstitial fluid glucose level. We used 6 different scenarios to ensure robust validation of the calculation. Over 96% of calculated blood glucose levels fit A+B zones of the Clarke Error Grid. No data set required any correction of model parameters during the time course of measuring. We successfully verified the possibility of calculating a continuous blood glucose level of subjects with type 1 diabetes. This study signals a successful transition of our research from an animal experiment to a human patient. Researchers can test our model with their data on-line at https://diabetes.zcu.cz. PMID- 27393800 TI - Application of Higuchi's fractal dimension from basic to clinical neurophysiology: A review. AB - BACKGROUND AND OBJECTIVE: For more than 20 years, Higuchi's fractal dimension (HFD), as a nonlinear method, has occupied an important place in the analysis of biological signals. The use of HFD has evolved from EEG and single neuron activity analysis to the most recent application in automated assessments of different clinical conditions. Our objective is to provide an updated review of the HFD method applied in basic and clinical neurophysiological research. METHODS: This article summarizes and critically reviews a broad literature and major findings concerning the applications of HFD for measuring the complexity of neuronal activity during different neurophysiological conditions. The source of information used in this review comes from the PubMed, Scopus, Google Scholar and IEEE Xplore Digital Library databases. RESULTS: The review process substantiated the significance, advantages and shortcomings of HFD application within all key areas of basic and clinical neurophysiology. Therefore, the paper discusses HFD application alone, combined with other linear or nonlinear measures, or as a part of automated methods for analyzing neurophysiological signals. CONCLUSIONS: The speed, accuracy and cost of applying the HFD method for research and medical diagnosis make it stand out from the widely used linear methods. However, only a combination of HFD with other nonlinear methods ensures reliable and accurate analysis of a wide range of neurophysiological signals. PMID- 27393801 TI - Heat transfer due to electroconvulsive therapy: Influence of anisotropic thermal and electrical skull conductivity. AB - BACKGROUND AND OBJECTIVES: This paper focuses on electroconvulsive therapy (ECT) and head models to investigate temperature profiles arising when anisotropic thermal and electrical conductivities are considered in the skull layer. The aim was to numerically investigate the threshold for which this therapy operates safely to the brain, from the thermal point of view. METHODS: A six-layer spherical head model consisting of scalp, fat, skull, cerebro-spinal fluid, grey matter and white matter was developed. Later on, a realistic human head model was also implemented. These models were built up using the packages from COMSOL Inc. and Simpleware Ltd. In these models, three of the most common electrode montages used in ECT were applied. Anisotropic conductivities were derived using volume constraint and included in both spherical and realistic head models. The bio-heat transferring problem governed by Laplace equation was solved numerically. RESULTS: The results show that both the tensor eigenvalues of electrical conductivity and the electrode montage affect the maximum temperature, but thermal anisotropy does not have a significant influence. Temperature increases occur mainly in the scalp and fat, and no harm is caused to the brain by the current applied during ECT. CONCLUSIONS: The work assures the thermal safety of ECT and also provides a numerical method to investigate other non-invasive therapies. PMID- 27393802 TI - Examination of nanoparticles as a drug carrier on blood flow through catheterized composite stenosed artery with permeable walls. AB - In this paper, we have discussed the influence of copper nanoparticles on a blood flow through composite stenosed artery with permeable walls. The nature of blood is discussed mathematically by considering it as viscous nanofluid. The study is carried out for a blood vessel under mild stenosis approximations and expressions of the temperature, velocity, resistance impedance to flow, wall shear stress and the pressure gradient is obtained by using corresponding boundary conditions. Results for the effects of permeability on blood flow through composite stenosis have been discussed graphically. The considered analysis also summarizes that the drug copper nanoparticles are efficient to reduce hemodynamics of stenosis and could be helpful to predict important uses for biomedical applications. Results indicate that nanoparticles are helpful as drug carriers to minimize the effects of resistance impedance to blood flow or coagulation factors due to stenosis. PMID- 27393803 TI - Detection of epileptic seizure in EEG signals using linear least squares preprocessing. AB - An epileptic seizure is a transient event of abnormal excessive neuronal discharge in the brain. This unwanted event can be obstructed by detection of electrical changes in the brain that happen before the seizure takes place. The automatic detection of seizures is necessary since the visual screening of EEG recordings is a time consuming task and requires experts to improve the diagnosis. Much of the prior research in detection of seizures has been developed based on artificial neural network, genetic programming, and wavelet transforms. Although the highest achieved accuracy for classification is 100%, there are drawbacks, such as the existence of unbalanced datasets and the lack of investigations in performances consistency. To address these, four linear least squares-based preprocessing models are proposed to extract key features of an EEG signal in order to detect seizures. The first two models are newly developed. The original signal (EEG) is approximated by a sinusoidal curve. Its amplitude is formed by a polynomial function and compared with the predeveloped spline function. Different statistical measures, namely classification accuracy, true positive and negative rates, false positive and negative rates and precision, are utilised to assess the performance of the proposed models. These metrics are derived from confusion matrices obtained from classifiers. Different classifiers are used over the original dataset and the set of extracted features. The proposed models significantly reduce the dimension of the classification problem and the computational time while the classification accuracy is improved in most cases. The first and third models are promising feature extraction methods with the classification accuracy of 100%. Logistic, LazyIB1, LazyIB5, and J48 are the best classifiers. Their true positive and negative rates are 1 while false positive and negative rates are 0 and the corresponding precision values are 1. Numerical results suggest that these models are robust and efficient for detecting epileptic seizure. PMID- 27393804 TI - Retinal blood vessel extraction using tunable bandpass filter and fuzzy conditional entropy. AB - BACKGROUND AND OBJECTIVES: Extraction of blood vessels on retinal images plays a significant role for screening of different opthalmologic diseases. However, accurate extraction of the entire and individual type of vessel silhouette from the noisy images with poorly illuminated background is a complicated task. To this aim, an integrated system design platform is suggested in this work for vessel extraction using a sequential bandpass filter followed by fuzzy conditional entropy maximization on matched filter response. METHODS: At first noise is eliminated from the image under consideration through curvelet based denoising. To include the fine details and the relatively less thick vessel structures, the image is passed through a bank of sequential bandpass filter structure optimized for contrast enhancement. Fuzzy conditional entropy on matched filter response is then maximized to find the set of multiple optimal thresholds to extract the different types of vessel silhouettes from the background. Differential Evolution algorithm is used to determine the optimal gain in bandpass filter and the combination of the fuzzy parameters. Using the multiple thresholds, retinal image is classified as the thick, the medium and the thin vessels including neovascularization. RESULTS: Performance evaluated on different publicly available retinal image databases shows that the proposed method is very efficient in identifying the diverse types of vessels. Proposed method is also efficient in extracting the abnormal and the thin blood vessels in pathological retinal images. The average values of true positive rate, false positive rate and accuracy offered by the method is 76.32%, 1.99% and 96.28%, respectively for the DRIVE database and 72.82%, 2.6% and 96.16%, respectively for the STARE database. Simulation results demonstrate that the proposed method outperforms the existing methods in detecting the various types of vessels and the neovascularization structures. CONCLUSIONS: The combination of curvelet transform and tunable bandpass filter is found to be very much effective in edge enhancement whereas fuzzy conditional entropy efficiently distinguishes vessels of different widths. PMID- 27393805 TI - Numerical simulation of osteocyte cell in response to directional mechanical loadings and mechanotransduction analysis: Considering lacunar-canalicular interstitial fluid flow. AB - The osteocyte cell is a bone cell that also functions as a bone mechanosensor. In this work, a three-dimensional (3D) fluid-structure interaction (FSI) model of an osteocyte cell under different mechanical loading conditions was used to obtain a better understanding of osteocyte cell behavior under different physiological conditions. In the current study, both fluid and solid parts of osteocyte cell were considered in order to allow for more accurate results. Five different loading conditions have been applied to the osteocyte cell, and consequently the different interstitial fluid flow velocities and shear stresses have been investigated. Furthermore, using a mathematical model, the change in the stimulus function value with shear stress and NO enzyme was revealed. This work suggests that changes in osteocyte morphology and direction of loadings affect cell stimulation. It was found that cell is mostly stimulated and expanded in the direction experiencing the most shear stress. Finally, the amount of cell stimulation was shown quantitatively and there was strong dependency between stimulus function, shear stress, calcium, and NO concentration. PMID- 27393806 TI - CometQ: An automated tool for the detection and quantification of DNA damage using comet assay image analysis. AB - BACKGROUND AND OBJECTIVE: DNA damage analysis plays an important role in determining the approaches for treatment and prevention of various diseases like cancer, schizophrenia and other heritable diseases. Comet assay is a sensitive and versatile method for DNA damage analysis. The main objective of this work is to implement a fully automated tool for the detection and quantification of DNA damage by analysing comet assay images. METHODS: The comet assay image analysis consists of four stages: (1) classifier (2) comet segmentation (3) comet partitioning and (4) comet quantification. Main features of the proposed software are the design and development of four comet segmentation methods, and the automatic routing of the input comet assay image to the most suitable one among these methods depending on the type of the image (silver stained or fluorescent stained) as well as the level of DNA damage (heavily damaged or lightly/moderately damaged). A classifier stage, based on support vector machine (SVM) is designed and implemented at the front end, to categorise the input image into one of the above four groups to ensure proper routing. Comet segmentation is followed by comet partitioning which is implemented using a novel technique coined as modified fuzzy clustering. Comet parameters are calculated in the comet quantification stage and are saved in an excel file. RESULTS: Our dataset consists of 600 silver stained images obtained from 40 Schizophrenia patients with different levels of severity, admitted to a tertiary hospital in South India and 56 fluorescent stained images obtained from different internet sources. The performance of "CometQ", the proposed standalone application for automated analysis of comet assay images, is evaluated by a clinical expert and is also compared with that of a most recent and related software-OpenComet. CometQ gave 90.26% positive predictive value (PPV) and 93.34% sensitivity which are much higher than those of OpenComet, especially in the case of silver stained images. The results are validated using confusion matrix and Jaccard index (JI). Comet assay images obtained after DNA damage repair by incubation in the nutrient medium were also analysed, and CometQ showed a significant change in all the comet parameters in most of the cases. CONCLUSIONS: Results show that CometQ is an accurate and efficient tool with good sensitivity and PPV for DNA damage analysis using comet assay images. PMID- 27393807 TI - A multi-resolution approach to localize neural sources of P300 event-related brain potential. AB - BACKGROUND AND OBJECTIVE: P300 is probably the most well-known component of event related brain potentials (ERPs). Using an oddball paradigm, a P300 component can be identified, that is, elicited by the target stimuli recognition. Since P300 is associated with attention and memory operations of the brain, investigation of this component can improve our understanding of these mechanisms. The present study is aimed at identifying the P300 generators in 30 healthy subjects aged 18 30 years using time-reduction region-suppression linearly constrained minimum variance (TR-LCMV) beamformer. METHODS: In our study, TR-LCMV beamformer with multi-resolution approach is proposed, coarse-resolution space to find the approximated coherent source locations, fine-resolution space to estimate covariance matrix for dimension reduction of determined regions, and normal resolution space to localize the P300 generators in the brain. RESULTS: Our results over simulated and real data showed that this approach is a suitable tool to the analysis of ERP fields with localizing superior and inferior frontal lobe, middle temporal gyrus, parietal lobe, and cingulate gyrus as the most prominent sources of P300. The result of P300 localization was finally compared with the other localization methods and it is demonstrated that enhanced performance is achieved. CONCLUSIONS: Our results showed that the P300 originates from a widespread neuronal network in the brain and not from a specific region. Our finding over simulated and real data demonstrated the ability of the TR-LCMV algorithm for P300 source localization. PMID- 27393808 TI - A new approach to configurable primary data collection. AB - BACKGROUND AND OBJECTIVES: The formats, semantics and operational rules of data processing tasks in genomics (and health in general) are highly divergent and can rapidly change. In such an environment, the problem of consistent transformation and loading of heterogeneous input data to various target repositories becomes a critical success factor. The objective of the project was to design a new conceptual approach to configurable data transformation, de-identification, and submission of health and genomic data sets. Main motivation was to facilitate automated or human-driven data uploading, as well as consolidation of heterogeneous sources in large genomic or health projects. METHODS: Modern methods of on-demand specialization of generic software components were applied. For specification of input-output data and required data collection activities, we propose a simple data model of flat tables as well as a domain-oriented graphical interface and portable representation of transformations in XML. Using such methods, the prototype of the Configurable Data Collection System (CDCS) was implemented in Java programming language with Swing graphical interfaces. The core logic of transformations was implemented as a library of reusable plugins. RESULTS: The solution is implemented as a software prototype for a configurable service-oriented system for semi-automatic data collection, transformation, sanitization and safe uploading to heterogeneous data repositories-CDCS. To address the dynamic nature of data schemas and data collection processes, the CDCS prototype facilitates interactive, user-driven configuration of the data collection process and extends basic functionality with a wide range of third party plugins. Notably, our solution also allows for the reduction of manual data entry for data originally missing in the output data sets. CONCLUSIONS: First experiments and feedback from domain experts confirm the prototype is flexible, configurable and extensible; runs well on data owner's systems; and is not dependent on vendor's standards. PMID- 27393809 TI - A new decision support model for preanesthetic evaluation. AB - BACKGROUND AND OBJECTIVE: The principal challenges in the field of anesthesia and intensive care consist of reducing both anesthetic risks and mortality rate. The ASA score plays an important role in patients' preanesthetic evaluation. In this paper, we propose a methodology to derive simple rules which classify patients in a category of the ASA scale on the basis of their medical characteristics. METHODS: This diagnosis system is based on MR-Sort, a multiple criteria decision analysis model. The proposed method intends to support two steps in this process. The first is the assignment of an ASA score to the patient; the second concerns the decision to accept-or not-the patient for surgery. RESULTS: In order to learn the model parameters and assess its effectiveness, we use a database containing the parameters of 898 patients who underwent preanesthesia evaluation. The accuracy of the learned models for predicting the ASA score and the decision of accepting the patient for surgery is assessed and proves to be better than that of other machine learning methods. Furthermore, simple decision rules can be explicitly derived from the learned model. These are easily interpretable by doctors, and their consistency with medical knowledge can be checked. CONCLUSIONS: The proposed model for assessing the ASA score produces accurate predictions on the basis of the (limited) set of patient attributes in the database available for the tests. Moreover, the learned MR-Sort model allows for easy interpretation by providing human-readable classification rules. PMID- 27393810 TI - A novel method for retinal exudate segmentation using signal separation algorithm. AB - Diabetic retinopathy is one of the major causes of blindness in the world. Early diagnosis of this disease is vital to the prevention of visual loss. The analysis of retinal lesions such as exudates, microaneurysms and hemorrhages is a prerequisite to detect diabetic disorders such as diabetic retinopathy and macular edema in fundus images. This paper presents an automatic method for the detection of retinal exudates. The novelty of this method lies in the use of Morphological Component Analysis (MCA) algorithm to separate lesions from normal retinal structures to facilitate the detection process. In the first stage, vessels are separated from lesions using the MCA algorithm with appropriate dictionaries. Then, the lesion part of retinal image is prepared for the detection of exudate regions. The final exudate map is created using dynamic thresholding and mathematical morphologies. Performance of the proposed method is measured on the three publicly available DiaretDB, HEI-MED and e-ophtha datasets. Accordingly, the AUC of 0.961 and 0.948 and 0.937 is achieved respectively, which are greater than most of the state-of-the-art methods. PMID- 27393811 TI - Decision support in addiction: The development of an e-health tool to assess and prevent risk of fatal overdose. The ORION Project. AB - BACKGROUND AND OBJECTIVE: The application of e-health technology to the field of substance use disorders is at a relatively early stage, and methodological quality is still variable. Few have explored the extent of utilization of communication technology in exploring risk perception by patients enrolled in substance abuse services. The Overdose RIsk InfOrmatioN (ORION) project is a European Commission funded programme, aimed to develop and pilot an e-health psycho-educational tool to provide information to drug using individuals about the risks of suffering a drug overdose. METHODS: In this article, we report on phase 1 (risk estimation), phase 2 (design), and phase 3 (feasibility) of the ORION project. RESULTS: The development of ORION e-health tool underlined the importance of an evidence-based intervention aimed in obtaining reliable evaluation of risk. The ORION tool supported a decision making process aimed at influencing the substance users' self-efficacy and the degree to which the substance users' understand risk factors. Therefore, its innovative power consisted in translating risks combination into a clear estimation for the user who will then appear more likely to be interested in his/her risk perception. CONCLUSION: Exploratory field testing and validation confirmed the next stage of evaluation, namely, collection of routine patient samples in study clinics. The associations between risk perception of overdose, engagement with the ORION tool and willingness to alter overdose risk factors, in a clinical setting across various EU member states will further confirm the ORION tool's generalisability and effectiveness. PMID- 27393813 TI - Editorial. PMID- 27393812 TI - The hemodynamic effects of the LVAD outflow cannula location on the thrombi distribution in the aorta: A primary numerical study. AB - Although a growing number of patients undergo LVAD implantation for heart failure treatment, thrombi are still the devastating complication for patients who used LVAD. LVAD outflow cannula location and thrombi generation sources were hypothesized to affect the thrombi distribution in the aorta. To test this hypothesis, numerical studies were conducted by using computational fluid dynamic (CFD) theory. Two anastomotic configurations, in which the LVAD outflow cannula is anastomosed to the anterior and lateral ascending aortic wall (named as anterior configurations and lateral configurations, respectively), are designed. The particles, whose sized are same as those of thrombi, are released at the LVAD output cannula and the aortic valve (named as thrombiP and thrombiL, respectively) to calculate the distribution of thrombi. The simulation results demonstrate that the thrombi distribution in the aorta is significantly affected by the LVAD outflow cannula location. In anterior configuration, the thrombi probability of entering into the three branches is 23.60%, while that in lateral configuration is 36.68%. Similarly, in anterior configuration, the thrombi probabilities of entering into brachiocephalic artery, left common carotid artery and left subclavian artery, is 8.51%, 9.64%, 5.45%, respectively, while that in lateral configuration it is 11.39%, 3.09%, 22.20% respectively. Moreover, the origins of thrombi could affect their distributions in the aorta. In anterior configuration, the thrombiP has a lower probability to enter into the three branches than thrombiL (12% vs. 25%). In contrast, in lateral configuration, the thrombiP has a higher probability to enter into the three branches than thrombiL (47% vs. 35%). In brief, the LVAD outflow cannula location significantly affects the distribution of thrombi in the aorta. Thus, in the clinical practice, the selection of outflow location of LVAD and the risk of thrombi formed in the left ventricle should be paid more attention than before. PMID- 27393814 TI - Characterization and expression of a novel caspase gene: Evidence of the expansion of caspases in Crassostrea gigas. AB - Caspases are a group of cysteine-aspartate proteases involved in apoptosis and a variety of non-apoptotic processes. In this study, a novel caspase gene was cloned and its potential role in apoptosis was investigated. The caspase gene (CgCasp 3/7) has an open reading frame of 1626bp encoding 541 amino acids containing the conserved functional domains and motifs of effector caspases. Its amino acid sequence shows low identity with the other effector caspases of Crassostrea gigas and contains a unique long intersubunit linker (IL). The CgCasp 3/7 mRNA was expressed highly in oocytes and then decreased gradually after fertilization, indicating CgCasp 3/7 could function in oocyte apoptosis. In adult tissues, it is located primarily in the gills and hepatopancreas. We examined the mRNA expression of CgCasp 3/7 in gills of oysters immersed in ambient (17 degrees C) or heated (27 degrees C) seawater. The thermal stress stimulated mRNA expression of CgCasp 3/7 by 2.5- and 4.1-fold at 2h and 6h post-treatment, respectively, indicating CgCasp3/7 was involved in the early response to thermal stress. To examine the function of the IL, CgCasp 3/7 and CgCasp 3/7-T (with a truncated IL) were expressed using an in vitro translation system and their DEVDase activity was measured. Both proteins showed a significantly higher level of DEVDase activity than control, but CgCasp3/7-T had lower DEVDase activity than CgCasp3/7, indicating CgCasp3/7 had DEVDase activity and the IL was required for maximal DEVDase activity. Our study adds to the complexity of caspases in C. gigas. PMID- 27393815 TI - Formation of size-controlled, denaturation-resistant lipid nanodiscs by an amphiphilic self-polymerizing peptide. AB - Nanodiscs are discoidal particles with a planar phospholipid bilayer enwrapped by proteins such as apolipoprotein A-I. Nanodiscs have been widely used for analyzing structures and functions of membrane proteins by dispersing them in solution. They are expected to be used as drug carriers and therapeutic agents. Amphiphilic peptides are known to form nanodiscs. However, the lipid-peptide nanodiscs are relatively unstable in solution, making them unsuitable for many applications. Here, we report the synthesis of an amphiphilic self-polymerizing peptide termed ASPP1, which polymerizes by intermolecular native chemical ligation reactions. ASPP1 spontaneously formed nanodiscs when added to phospholipid vesicles without using detergents. The diameter of the planar lipid bilayer in the nanodiscs was controlled by the lipid:peptide molar ratio. ASPP1 nanodiscs exhibited greater stability at high temperatures or in the presence of urea than nanodiscs formed by the non-polymerizing amphiphilic peptide or apolipoprotein A-I. Average and maximal degrees of ASPP1 polymerization were 2.4 and 12, respectively. Self-polymerization of the peptide appears to be responsible for stabilization of the nanodiscs. Our results open a new avenue for the development of nanodisc technology. PMID- 27393816 TI - Building Relationships: The Power of Networking. PMID- 27393817 TI - Journal of Emergency Nursing Updates. PMID- 27393818 TI - The Culture of Care Interfacing Internal Validity of Emergency Severity Index. PMID- 27393819 TI - Response. PMID- 27393820 TI - Intravenous Catheters and Blood Samples. PMID- 27393821 TI - Response. PMID- 27393822 TI - Emergency Nursing Review Questions: July 2016. PMID- 27393824 TI - ? PMID- 27393823 TI - Passing the Experience Talks Baton. PMID- 27393825 TI - Association between vehicular emissions and cardiorespiratory disease risk in Brazil and its variation by spatial clustering of socio-economic factors. AB - Many studies have suggested that socio-economic factors are strong modifiers of human vulnerability to air pollution effects. Most of these studies were performed in developed countries, specifically in the US and Europe. Only a few studies have been performed in developing countries, and analyzed small regions (city level) with no spatial disaggregation. The aim of this study was to assess the association between vehicle emissions and cardiorespiratory disease risk in Brazil and its modification by spatial clustering of socio-economic conditions. We used a quantile regression model to estimate the risk and a geostatistical approach (K means) to execute spatial cluster analysis. We performed the risk analysis in three stages. First, we analyzed the entire study area (primary analysis), and then we conducted a spatial cluster analysis based on various municipal-level socio-economic factors, followed by a sensitivity analysis. We studied 5444 municipalities in Brazil between 2008 and 2012. Our findings showed a significant association between cardiorespiratory disease risk and vehicular emissions. We found that a 15% increase in air pollution is associated with a 6% increase in hospital admissions rates. The results from the spatial cluster analysis revealed two groups of municipalities with distinct sets of socio economic factors and risk levels of cardiorespiratory disease related to exposure to vehicular emissions. For example, for vehicle emissions of PM in 2008, we found a relative risk of 4.18 (95% CI: 3.66, 4.93) in the primary analysis; in Group 1, the risk was 0.98 (95% CI: 0.10, 2.05) while in Group 2, the risk was 5.56 (95% CI: 4.46, 6.25). The risk in Group 2 was 480% higher than the risk in Group 1, and 35% higher than the risk in the primary analysis. Group 1 had higher values (3rd quartile) for urbanization rate, highway density, and GDP; very high values (>=3rd quartile) for population density; median values for distance from the capital; and lower values (1st quartile) for rural population density. Group 2 had lower values (1st quartile) urbanization rate; median values for highway density, GDP, and population density; between median and third quartile values for distance from the capital; and higher values (3rd quartile) for rural population density. Our findings suggest that socio-economic factors are important modifiers of the human risk of cardiorespiratory disease due to exposure to vehicle emissions in Brazil. Our study provides support for creating effective public policies related to environmental health that are targeted to high-risk populations. PMID- 27393826 TI - Effects of cortisol on the heart: characterization of myocardial involvement in cushing's disease by longitudinal cardiac MRI T1 mapping. AB - PURPOSE: Cushing's disease (CD) is associated with alterations in cardiac geometry and function, shown to be reversible after treatment. Our aim was to study cortisol-related changes in myocardial content in CD at baseline and after treatment using MR myocardial T1 times. MATERIALS AND METHODS: This is a longitudinal study performed in 10 patients with active CD matched with 10 hypertensive and 10 healthy controls. All subjects had MR after CD diagnosis and 6 months after cortisol normalization. The 1.5 Tesla MR protocol included left ventricular geometry and function assessment and MOLLI sequences before and after contrast injection as well as late gadolinium enhancement. RESULTS: At baseline, native myocardial T1 was significantly higher in CD patients compared with controls and the hypertensive group (1056 +/- 139 ms versus 929 +/- 80 ms, P = 0.023; 1056 +/- 139 ms versus 952 +/- 51, P = 0.049). After treatment, native and postcontrast myocardial T1 decreased in CD patients versus controls (1056 +/- 139 ms versus 832 +/- 78, P = 0.006 and 483 +/- 69 ms versus 395 +/- 39 ms, P = 0.010) reaching values even lower than found in controls (P = 0.038 and P = 0.001, respectively). CONCLUSION: Native myocardial T1 is increased in Cushing's disease independently from hypertension and notably decreases after effective treatment, highlighting its potential to detect subclinical diffuse myocardial involvement in this condition. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:147-156. PMID- 27393827 TI - A novel, sensitive and label-free loop-mediated isothermal amplification detection method for nucleic acids using luminophore dyes. AB - Electrochemiluminescence (ECL) has been widely rendered for nucleic acid testing. Here, we integrate loop-mediated isothermal amplification (LAMP) with ECL technique for DNA detection and quantification. The target LAMP DNA bound electrostatically with [Ru(bpy)3](+2) on the carbon electrode surface, and an ECL reaction was triggered by tripropylamine (TPrA) to yield luminescence. We illustrated this method as a new and highly sensitive strategy for the detection of sequence-specific DNA from different meat species at picogram levels. The proposed strategy renders the signal amplification capacities of TPrA and combines LAMP with inherently high sensitivity of the ECL technique, to facilitate the detection of low quantities of DNA. By leveraging this technique, target DNA of Sus scrofa (pork) meat was detected as low as 1pg/uL (3.43*10( 1)copies/uL). In addition, the proposed technique was applied for detection of Bacillus subtilis DNA samples and detection limit of 10pg/uL (2.2*10(3)copies/uL) was achieved. The advantages of being isothermal, sensitive and robust with ability for multiplex detection of bio-analytes makes this method a facile and appealing sensing modality in hand-held devices to be used at the point-of-care (POC). PMID- 27393828 TI - Cell signaling regulation by protein phosphorylation: a multivariate, heterogeneous, and context-dependent process. AB - Proper spatiotemporal regulation of protein phosphorylation in cells and tissues is required for normal development and homeostasis, but aberrant protein phosphorylation regulation leads to various diseases. The study of signaling regulation by protein phosphorylation is complicated in part by the sheer scope of the kinome and phosphoproteome, dependence of signaling protein functionality on cellular localization, and the complex multivariate relationships that exist between protein phosphorylation dynamics and the cellular phenotypes they control. Additional complexities arise from the ability of microenvironmental factors to influence phosphorylation-dependent signaling and from the tendency for some signaling processes to occur heterogeneously among cells. These considerations should be taken into account when measuring cell signaling regulation by protein phosphorylation. PMID- 27393830 TI - Lignin-rich biomass of cotton by-products for biorefineries via pyrolysis. AB - Pyrolysis was demonstrated to investigate the thermal decomposition characteristics and potential of lignin-rich cotton by-products cotton exocarp (CE) and spent mushroom substrate consisted of cotton by-products (MSC) for biorefineries. The chemical component and structure alteration of CE and MSC was found to affect their thermochemical behaviors. The bio-oil yield from CE was 58.13wt% while the maximum yield from MSC was 45.01% at 600 degrees C. The phenolic compounds obtained from CE and MSC were 33.9% and 39.2%, respectively. The yield of acetic acid from MSC between 400 and 600 degrees C was about 30-38% lower than that from CE, which suggests the high quality of bio-oil was obtained. Biochar from MSC via slow pyrolysis had a high mass yield (44.38wt%) with well developed pore structure. PMID- 27393831 TI - High-efficiency l-lactic acid production by Rhizopus oryzae using a novel modified one-step fermentation strategy. AB - In this study, lactic acid fermentation by Rhizopus oryzae was investigated using the two different fermentation strategies of one-step fermentation (OSF) and conventional fermentation (CF). Compared to CF, OSF reduced the demurrage of the production process and increased the production of lactic acid. However, the qp was significantly lower than during CF. Based on analysis of MU, qs and qp, a novel modified OSF strategy was proposed. This strategy aimed to achieve a high final concentration of lactic acid, and a high qp by R. oryzae. In this strategy, the maximum lactic acid concentration and productivity of the lactic acid production stage reached 158g/l and 5.45g/(lh), which were 177% and 366% higher, respectively, than the best results from CF. Importantly, the qp and yield did not decrease. This strategy is a convenient and economical method for l-lactic acid fermentation by R. oryzae. PMID- 27393829 TI - Extracting structural and functional features of widely distributed biological circuits with single cell resolution via tissue clearing and delivery vectors. AB - The scientific community has learned a great deal from imaging small and naturally transparent organisms such as nematodes and zebrafish. The consequences of genetic mutations on their organ development and survival can be visualized easily and with high-throughput at the organism-wide scale. In contrast, three dimensional information is less accessible in mammalian subjects because the heterogeneity of light-scattering tissue elements renders their organs opaque. Likewise, genetically labeling desired circuits across mammalian bodies is prohibitively slow and costly via the transgenic route. Emerging breakthroughs in viral vector engineering, genome editing tools, and tissue clearing can render larger opaque organisms genetically tractable and transparent for whole-organ cell phenotyping, tract tracing and imaging at depth. PMID- 27393832 TI - Co-combustion of bituminous coal and biomass fuel blends: Thermochemical characterization, potential utilization and environmental advantage. AB - The thermochemical characteristics and gaseous trace pollutant behaviors during co-combustion medium-to-low ash bituminous coal with typical biomass residues (corn stalk and sawdust) were investigated. Lowering of ignition index, burnout temperature and activation energy in the major combustion stage are observed in the coal/biomass blends. The blending proportion of 20% and 30% are regarded as the optimum blends for corn stalk and sawdust, respectively, in according the limitations of heating value, activation energy, flame stability and base/acid ratio. The reductions of gaseous As, Cd, Cu, Pb, Zn and polycyclic aromatic hydrocarbon (PAHs) were 4.5%, 7.8%, 6.3%, 9.8%, 9.4% and 17.4%, respectively, when co-combustion coal with 20% corn stalk. The elevated capture of trace elements were found in coal/corn stalk blend, while the coal/sawdust blend has the better PAHs control potential. The reduction mechanisms of gaseous trace pollutants were attributed to the fuel property, ash composition and relative residence time during combustion. PMID- 27393833 TI - Dissolved air flotation and centrifugation as methods for oil recovery from ruptured microalgal cells. AB - Solvent-free microalgal lipid recovery is highly desirable for safer, more sustainable and more economical microalgal oil production. Dispersed air flotation and centrifugation were evaluated for the ability to separate oil and debris from a slurry mixture of osmotically fractured Chaetoceros muelleri cells with and without utilizing collectors. Microalgal oil partially phase-separated as a top layer and partially formed an oil-in-water emulsion. Although collectors, such as sodium dodecyl sulphate enhanced selective flotation, by just adjusting the pH and cell concentration of the mixture, up to 78% of the lipids were recovered in the froth. Using centrifugation of fractured microalgal slurry resulted in removal of 60% cell debris and up to 68.5% of microalgal oil was present in the supernatant. Both methods, centrifugation and flotation provided options for separation of microalgal oil from C. muelleri slurry with similar fatty acid recoveries of 57% and 60%, respectively. PMID- 27393834 TI - Evaluation of hydrogen and methane production from sugarcane bagasse hemicellulose hydrolysates by two-stage anaerobic digestion process. AB - This study aimed at optimizing the net energy recovery from hydrogen and methane production through anaerobic digestion of the hemicellulose hydrolysate (HH) obtained by desirable conditions (DC) of autohydrolysis pretreatment (AH) of sugarcane bagasse (SB). Anaerobic digestion was carried out in a two-stage (acidogenic-methanogenic) batch system where the acidogenic phase worked as a hydrolysis and biodetoxification step. This allowed the utilization of more severe AH pretreatment conditions, i.e. T=178.6 degrees C and t=55min (DC3) and T=182.9 degrees C and t=40.71min (DC4). Such severe conditions resulted in higher extraction of hemicelluloses from SB (DC1=68.07%, DC2=48.99%, DC3=77.40% and DC4=73.90%), which consequently improved the net energy balance of the proposed process. The estimated energy from the combustion of both biogases (H2 and CH4) accumulated during the two-stage anaerobic digestion of HH generated by DC4 condition was capable of producing a net energy of 3.15MJ.kgSB(-1)dry weight. PMID- 27393835 TI - Selective natural induction of laccases in Pleurotus sajor-caju, suitable for application at a biofuel cell cathode at neutral pH. AB - Laccases are multicopper oxidoreductases with broad substrate specificity and are applied in biofuel cells at the cathode to improve its oxygen reduction performance. However, the production of laccases by e.g. fungi is often accompanied by the need of synthetic growth supplements for increased enzyme production. In this study we present a strategy for the white-rot fungus Pleurotus sajor-caju for natural laccase activity induction using lignocellulose substrates and culture supernatant of Aspergillus nidulans. P. sajor-caju laccases were secreted into the supernatant, which was directly used at a carbon nanotube buckypaper cathode in a biofuel cell. Maximal current densities of 148+/-3MUAcm(-2) and -102+/-9MUAcm(-2) at 400mV were achieved at pH 5 and 7, respectively. Variations in cathode performance were observed with culture supernatants produced under different conditions due to the induction of specific laccases. PMID- 27393836 TI - Association between prior appendectomy and/or tonsillectomy in women and subsequent pregnancy rate: a cohort study. AB - OBJECTIVE: To study pregnancy rates after appendectomy and/or tonsillectomy. DESIGN: Population-based cohort study using the United Kingdom (U.K.) primary health care-based Clinical Practice Research Datalink (CPRD). SETTING: Not applicable. PATIENT(S): Female patients who underwent appendectomy, tonsillectomy, or both from 1987 to 2012 and appropriate comparators. INTERVENTION(S): Timed follow-up until first pregnancy after surgery. The association between prior surgery and subsequent pregnancy was determined with the use of Cox regression models. MAIN OUTCOME MEASURE(S): Pregnancy rate and time to first pregnancy after surgery. RESULT(S): The analyses included 54,675 appendectomy-only patients, 112,607 tonsillectomy-only patients, 10,340 patients who had both appendectomy and tonsillectomy, and 355,244 comparators matched for exact age and practice from the rest of female patients in the database. There were 29,732 (54.4%), 60,078 (53.4%), and 6,169 (59.7%) pregnancies in the appendectomy-only, tonsillectomy-only, and both appendectomy tonsillectomy cohorts, respectively versus 155,079 (43.7%) in the comparator cohort during a mean follow-up of 14.7 +/- 9.7 years. Adjusted hazard ratios (HRs) for subsequent birth rates were 1.34 (95% confidence interval [CI] 1.32-1.35), 1.49 (95% CI 1.48 1.51), and 1.43 (95% CI 1.39-1.47), respectively. Time to pregnancy was shortest after both appendectomy and tonsillectomy followed by appendectomy only and then tonsillectomy only compared with the rest of the population. CONCLUSION(S): Appendectomy and/or tonsillectomy was associated with increased subsequent pregnancy rates and shorter time to pregnancy. The effect of the surgical procedures on the pregnancy outcome was cumulative. PMID- 27393837 TI - Breast arterial calcifications on mammography and coronary artery disease: A new screening tool for cardiovascular disease? PMID- 27393838 TI - Reversible acute renal failure in patients with takotsubo syndrome. PMID- 27393839 TI - Quantitative detection of inducible ischemia during dobutamine stress by speckle tracking echocardiography: A dream comes true. PMID- 27393840 TI - Thrombosis in a right wrap around coronary artery leading to takotsubo syndrome phenotype diagnosed as an acute myocardial infarction: Lingering afterthoughts. PMID- 27393841 TI - Desalinated seawater supply and all-cause mortality in hospitalized acute myocardial infarction patients from the Acute Coronary Syndrome Israeli Survey 2002-2013. AB - BACKGROUND: Consuming desalinated seawater (DSW) as drinking water (DW) may reduce magnesium in water intake causing hypomagnesemia and adverse cardiovascular effects. METHODS: We evaluated 30-day and 1-year all-cause mortality of acute myocardial infarction (AMI) patients enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) during 2002-2013. Patients (n=4678) were divided into 2 groups: those living in regions supplied by DSW (n=1600, 34.2%) and non-DSW (n=3078, 65.8%). Data were compared between an early period [2002-2006 surveys (n=2531) - before desalination] and a late period [2008 2013 surveys (n=2147) - during desalination]. RESULTS: Thirty-day all-cause mortality was significantly higher in the late period in patients from the DSW regions compared with those from the non-DSW regions (HR=2.35 CI 95% 1.33-4.15, P<0.001) while in the early period there was no significant difference (HR=1.37 CI 95% 0.9-2, P=0.14). Likewise, there was a significantly higher 1-year all cause mortality in the late period in patients from DSW regions compared with those from the non-DSW regions (HR=1.87 CI 95% 1.32-2.63, P<0.0001), while in the early period there was no significant difference (HR=1.17 CI 95% 0.9-1.5, P=0.22). Admission serum magnesium level (M+/-SD) in the DSW regions (n=130) was 1.94+/-0.24mg/dL compared with 2.08+/-0.27mg/dL in 81 patients in the non-DSW (P<0.0001). CONCLUSIONS: Higher 30-day and 1-year all-cause mortality in AMI patients, found in the DSW regions may be attributed to reduced magnesium intake secondary to DSW consumption. PMID- 27393842 TI - Inadequate stroke prevention in Korean atrial fibrillation patients in the post warfarin era. AB - BACKGROUND: Anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is recommended for atrial fibrillation (AF) patients who are at a high risk for stroke. This study aimed to investigate the utilization of anticoagulants since the introduction of DOACs in South Korea. METHODS: This was a cross-sectional study using claim-based national data from 2011 to 2014 derived from the Aged Patient Sample (APS) compiled by the Health Insurance Review & Assessment Service (HIRA). Patients with a high risk for thromboembolism were identified as those having a CHA2DS2-VASc (congestive heart failure, hypertension, age>=75, diabetes mellitus, stroke (or transient ischemic attack), vascular disease, sex) score of >=2. Patients at a high risk for bleeding with an ATRIA (anticoagulation and risk factors in atrial fibrillation) bleeding score of >4 were excluded. Anticoagulant underutilization was estimated in these high-risk patients. Demographic and clinical factors associated with warfarin and DOAC underutilization were explored using a logistic regression model. RESULTS: Anticoagulant underutilization among high-risk patients for stroke decreased from 68% to 62.5% between 2011 and 2014; however, there was further scope for improvement. The risk factors for underutilization were identified as follows: female sex, old age, having medical aid insurance, presence of vascular disease, and limited anticoagulant options. CONCLUSIONS: Our study demonstrates that a large population of AF patients in South Korea failed to obtain adequate stroke prevention treatment, even in the era of DOAC usage. A more aggressive approach to provide optimal antithrombotic therapy is warranted. PMID- 27393843 TI - Recurrence of permanent junctional re-entry tachycardia: Indication for ablation of the junctional pathway. PMID- 27393844 TI - Pericardial enhancement using multimodality imaging in a rare auto-inflammatory disorder. PMID- 27393845 TI - The role of FDG-PET-CT in pediatric cardiac patients and patients with congenital heart defects. AB - AIM: Medical imaging by using FDG-PET/CT (PET-CT) can detect, confirm or eliminate with high sensitivity areas of suspected infections in case of persistent fever of unknown origin in combination with other bacteriological examinations. The aim of this study was to assess the potential role of PET-CT in detecting or excluding infections or other inflammatory processes in patients with congenital heart defects (CHD). In addition we wanted to evaluate the practical impact of PET-CT on the subsequent clinical management. METHODS: In this retrospective study we analyzed the data of all CHD patients who underwent PET-CT over a 5year period in our institution. The results were then evaluated with regard to the potential impact on clinical decision making. RESULTS: Between 2010 and 2015 PET-CT was performed in 30 patients. The mean age was 26years (SD 15years, range 1 to 66years). The diagnoses covered a large field of CHD. 11 patients (4/11 with assist device) were assessed before heart transplantation; suspected malignancies or infections were excluded and transplant listing was possible. In another 5/6 patients suspected assist device infection could be confirmed with PET/CT. Endocarditis was suspected in 13 patients, 2 of whom underwent previous MRI without confirmation and ECHO was inconclusive. Endocarditis was finally excluded in 5/13 patients but confirmed in 8/13 patients by PET-CT. CONCLUSION: In this study we could show a high sensitivity of PET-CT for specific localization of infections and with high impact on subsequent therapy. Based on this results clinical management could be targeted and adapted. We could demonstrate that PET-CT has a high impact on the subsequent clinical therapy. PMID- 27393846 TI - Percutaneous Implantation of the self-expanding valve Prosthesis a patient with homozygous familial hypercholesterolemia severe aortic stenosis and porcelain aorta. AB - Transcatheter aortic valve implantation (TAVI) has shown favorable outcomes in patients with severe symptomatic aortic valve stenosis who are at high surgical risk or inappropriate for open heart surgery. However, concerns exist over treating patients who have porcelain aorta and familial hypercholesterolemia, due to the potential complications of aortic root and aortic annulus. In this case report, we present a patient with familial hypercholesterolemia, symptomatic severe aortic stenosis, previous coronary artery bypass grafting and porcelain aorta, who was successfully treated with TAVI using a CoreValve. PMID- 27393847 TI - Autonomic instability and asystole: Broadening the differential diagnosis of cardiac arrhythmias. PMID- 27393848 TI - Medication adherence and persistence according to different antihypertensive drug classes: A retrospective cohort study of 255,500 patients. AB - BACKGROUND: Suboptimal adherence to antihypertensives leads to adverse clinical outcomes. This study aims to determine and compare medication adherence and persistence to different first-line antihypertensive drug classes in a large cohort. METHODS: A cohort study was performed using claims data for prescriptions in the German statutory health insurance scheme that insures approximately 90% of the population. A total of 255,500 patients with a first prescription of an antihypertensive were included and followed for 24months. Persistence was determined based on gaps in continuous dispensation. Adherence was analyzed by calculating the medication possession ratio (MPR). RESULTS: Within a 2-year period, 79.3% of all incident users of antihypertensive monotherapy met the classification of non-persistence (gap >0.5 times the number of days supplied with medication) and 56.3% of non-adherence (MPR<0.8). Beta-blockers (42.5%) and angiotensin-converting enzyme inhibitors (31.9%) were the most widely prescribed drug classes. Non-persistence and non-adherence were highest for diuretics (85.4%, n=6149 and 66.3%, n=4774) and lowest for beta-blockers (77.6%, n=76,729 and 55.2%, n=54,559). The first gap of antihypertensive medication occurred in median 160-250days after initiation, and the average medication possession ratio for all drug classes was less than 0.8. Fixed combinations with diuretics showed a 19.8% lower chance for non-adherence (OR=0.802, 99.9% CI=[0.715-0.900], p<0.001) and an 8.4% lower hazard for non-persistence (HR 0.916, 99.9% CI=[0.863 0.973], p<0.001) compared with monotherapies. CONCLUSIONS: This large cohort study reveals important differences in 2-year adherence and persistence between antihypertensives that were lowest for diuretics. Fixed-dose combinations with diuretics may facilitate adherence compared to single substance products. However, effective strategies to improve adherence to antihypertensives are needed regardless of drug class. PMID- 27393849 TI - Iatrogenic coronary artery stenosis: A multiform disease. PMID- 27393850 TI - Involvement of exogenous H2S in recovery of cardioprotection from ischemic post conditioning via increase of autophagy in the aged hearts. AB - BACKGROUND: Hydrogen sulfide (H2S), which is a member of the gasotransmitter family, plays an important physiological and pathological role in cardiovascular system. Ischemic post-conditioning (PC) provides myocardial protective effect in the young hearts but not in the aged hearts. Exogenous H2S restores PC-induced cardioprotection by inhibition of mitochondrial permeability transition pore (mPTP) in the aged hearts. However, whether H2S contributes to the recovery of PC induced cardioprotection via up-regulation of autophagy in the aged hearts is unclear. METHODS: The isolated aged rat hearts (24-months-old, 450-500g) and aged cardiomyocytes-induced by d-galactose were exposed to an ischemia/reperfusion (I/R) and PC protocol. RESULTS: We found PC lost cardioprotection in the aged hearts and cardiomyocytes. NaHS (a H2S donor) significantly restored cardioprotection of PC through decreasing myocardial damage, infarct size, and apoptosis, improving cardiac function, increasing cell viability and autophagy in the aged hearts and cardiomyocytes. 3-MA (an autophagy inhibitor) abolished beneficial effect of NaHS in the aged hearts. In addition, in the aged cardiomyocytes, NaHS up-regulated AMPK/mTOR pathway, and the effect of NaHS on PC was similar to the overexpression of Atg 5, treatment of AICAR (an AMPK activator) or Rapamycin (a mTOR inhibitor, an autophagy activator), respectively. CONCLUSIONS: These results suggest that exogenous H2S restores cardioprotection from PC by up-regulation of autophagy via activation of AMPK/mTOR pathway in the aged hearts and cardiomyocytes. PMID- 27393851 TI - Layer specific strain measurement and its relationship to heart failure indicators in systemic autoimmune disorder patients: A multi-layer transthoracic echocardiography study. PMID- 27393852 TI - SIRT3 in cardiovascular diseases: Emerging roles and therapeutic implications. AB - SIRT3 belongs to a highly conserved protein family of histone deacetylases and it is rich in mitochondria. As acetyl-modification is one of the important post translational modifications that prevail in the mitochondria, it is not surprising that SIRT3 plays a key regulatory role in this organelle. SIRT3 has a wide range of substrates that are involved in the physiological and pathological processes of oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. These pathophysiological processes are considered as the underlying mechanisms of diseases like cardiac hypertrophy, myocardial infarction and heart failure, indicating the potential roles of SIRT3 in cardiovascular diseases. In this review, we will summarize the emerging roles and therapeutic implications of SIRT3 in cardiovascular diseases by providing an update on the latest understanding of its functions. PMID- 27393853 TI - A new novolimus-eluting bioresorbable scaffold for large coronary arteries: an OCT study of acute mechanical performance. AB - AIMS: To evaluate the acute performance of a novolimus-eluting bioresorbable scaffold (BRS) with a nominal diameter of 4.0mm (DESolve(r) XL) using optical coherence tomography (OCT) in terms of appropriate scaffold deployment. METHODS AND RESULTS: Ten patients (55.6% male, mean age 60.0 y) undergoing OCT-guided scaffold implantation were enrolled consecutively in this retrospective study. Using data from the final pullback, the following indexes were calculated: mean and minimum area, residual area stenosis, incomplete strut apposition, tissue prolapse, eccentricity and symmetry indexes, strut fracture, and edge dissection. The clinical indication for the procedure was acute coronary syndrome in roughly half (55.5%) of the cases. All three main vessels were affected equally. The maximum post-dilatation balloon inflation pressure was 14.7+/-4.2atm. OCT analysis showed a lumen area of 11.4+/-1.9mm(2) and a scaffold area of 11.5+/ 2.1mm(2). Mean residual area stenosis was 28.6%. No strut fractures or edge dissections were apparent. The mean eccentricity index was 0.65+/-0.16 and the mean symmetry index 0.39+/-0.25. CONCLUSION: The size of large vessels does not adversely influence acute mechanical performance as assessed by the eccentricity and symmetry indexes. No adverse cardiac event occurred during the hospital stay or the 30-day follow-up. It is feasible to treat large vessels with the DESolve(r) XL BRS. PMID- 27393854 TI - Lipoprotein(a) and risk of sudden cardiac death in middle-aged Finnish men: A new prospective cohort study. AB - BACKGROUND: Lipoprotein(a) [Lp(a)] is an established and independent risk factor for cardiovascular outcomes. However, the relationship of Lp(a) with risk of sudden cardiac death (SCD) is unknown. We aimed to assess the association of Lp(a) with risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 1881 men aged 42-61years at recruitment. METHODS AND RESULTS: Plasma Lp(a) concentration was assessed at baseline and repeat measurements made several years apart. After a median follow-up of 24.7years, 141 SCDs were recorded. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and were corrected for within-person variability in Lp(a) levels. The regression dilution ratio of loge Lp(a) adjusted for age was 0.84 (95% CI: 0.81-0.88). Lipoprotein(a) levels were log-linearly associated with risk of SCD. In analyses adjusted for established risk factors, the HR (95% CI) for SCD per 1 standard deviation (3.56 fold) higher baseline loge Lp(a) was 1.24 (1.05-1.47; P=0.013). This remained consistent on further adjustment for alcohol consumption, resting heart rate, lipids, and C-reactive protein 1.23 (1.04-1.46; P=0.018). HRs remained unchanged after accounting for incident coronary events and did not vary importantly in several relevant clinical subgroups. Adding Lp(a) to a SCD risk prediction model did not significantly improve risk discrimination beyond established risk factors, but improved the continuous net reclassification 30.2% (1.1 to 59.2%, P=0.042). CONCLUSIONS: Available evidence shows a continuous and independent association between Lp(a) levels and risk of SCD. Further research is needed to replicate these findings. PMID- 27393855 TI - Angiographically intermediate left main bifurcation disease assessment by frequency domain optical coherence tomography (FD-OCT). PMID- 27393856 TI - Hypothermia is an independent predictor of short and intermediate term mortality in acute systolic heart failure: Insights from the ESCAPE trial. AB - INTRODUCTION: Admission hypothermia is associated with increased mortality in patients hospitalized with sepsis, trauma or stroke. We hypothesized that hypothermia on admission in patients with acute systolic heart failure (HF) would be associated with worse survival. METHODS: Using ESCAPE trial data, we compared patients hospitalized with acute systolic HF with admission temperature <=35.5 degrees C or >35.5 degrees C. The study endpoints were 30-day and 6-month all cause mortality. RESULTS: Among the 398 patients (mean age 56years, 74% men) who had body temperature recorded on hospital admission, 23 had a temperature <=35.5 degrees C (hypothermia) and 375 patients had a temperature >35.5 degrees C. By univariate comparison, hypothermic patients had a higher blood urea nitrogen (BUN) level (46.6versus 34.6mg/dL, P=0.04) and creatinine level (1.85 versus 1.49mg/dL, P=0.035) and higher frequency of malignancy (26.1% versus 6.1%, P=0.001). There was a significant correlation between admission temperature and body mass index (r=0.201, P<0.0001). Patients with temperature<=35.5 degrees C had a higher 30-day (17.4% versus 4.3%, univariate OR 4.724, 95% CI 1.439-15.509, P=0.01) and 6-month (43.5% versus 18.1%, univariate OR 3.473, 95% CI 1.462-8.25, P=0.005) all-cause mortality. Cox proportional hazard analysis revealed that admission temperature <=35.5 degrees C is an independent predictor of mortality (hazard ratio 2.222, 95% CI 1.117-4.420, P=0.023). Kaplan-Meier analysis comparing survival in patients with admission temperature <=35.5 degrees C or >35.5 degrees C showed a significant inter-group difference in survival (log-rank P value=0.001). CONCLUSION: Admission body temperature <=35.5 degrees C is an independent predictor of short and intermediate term mortality in patients hospitalized with acute systolic HF. PMID- 27393857 TI - Could prioritisation by emergency medicine dispatchers be improved by using computer-based decision support? A cohort of patients with chest pain. AB - BACKGROUND: To evaluate whether a computer-based decision support system could improve the allocation of patients with acute coronary syndrome (ACS) or a life threatening condition (LTC). We hypothesised that a system of this kind would improve sensitivity without compromising specificity. METHODS: A total of 2285 consecutive patients who dialed 112 due to chest pain were asked 10 specific questions and a prediction model was constructed based on the answers. We compared the sensitivity of the dispatchers' decisions with that of the model based decision support model. RESULTS: A total of 2048 patients answered all 10 questions. Among the 235 patients with ACS, 194 were allocated the highest prioritisation by dispatchers (sensitivity 82.6%) and 41 patients were given a lower prioritisation (17.4% false negatives). The allocation suggested by the model used the highest prioritisation in 212 of the patients with ACS (sensitivity of 90.2%), while 23 patients were underprioritised (9.8% false negatives). The results were similar when the two systems were compared with regard to LTC and 30-day mortality. This indicates that computer-based decision support could be used either for increasing sensitivity or for saving resources. Three questions proved to be most important in terms of predicting ACS/LTC, [1] the intensity of pain, [2] the localisation of pain and [3] a history of ACS. CONCLUSION: Among patients with acute chest pain, computer-based decision support with a model based on a few fundamental questions could improve sensitivity and reduce the number of cases with the highest prioritisation without endangering the patients. PMID- 27393858 TI - Diagnostic comparison of cardiac magnetic resonance with endomyocardial biopsy in patients with dilated cardiomyopathy: A segment-by-segment analysis. PMID- 27393859 TI - Serum neprilysin and recurrent hospitalizations after acute heart failure. PMID- 27393860 TI - Impact of cardiovascular risk factors and disease on length of stay and mortality in patients with acute coronary syndromes. AB - BACKGROUND: Traditional risk factors for cardiovascular disease (CVD) have been thoroughly investigated. We aimed to investigate the impact of comorbid cardiovascular risk factors and diseases on length of stay (LOS) and mortality in patients presenting with acute coronary syndromes (ACS). METHODS: We examined prevalence of CVD, LOS and mortality from 25,287 consecutive admissions for ACS from seven hospitals across North West England between 2000 and 2013 using the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) protocol using ICD-10 and OPCS-4 coding systems. RESULTS: Mean LOS was 7.0days and there were 9653 (38.2%) deaths in the ACS cohort over the 13-year period. Hypertension and hyperlipidaemia were associated with decreased LOS (6.95 and 4.8days respectively, P<0.001) and mortality (36.8% and 19.4% respectively, P<0.001), as was angina pectoris (5.4days and 33.5%, P<0.001). Type 2 diabetes was associated with increased LOS and mortality (7.8days, P<0.05; 44.4%, P<0.001), whereas type 1 diabetes was associated with increased mortality only (7.0days, P=0.42; 41.3%, P<0.001). Other concomitant CVD was associated with an increased LOS and mortality: peripheral vascular disease (8.6days, P<0.05; 53%, P<0.001), atrial fibrillation (10.9days, P<0.001; 63.5%, P<0.001), cerebrovascular disease (15.9days, P<0.001; 76%, P<0.001), heart failure (11days, P<0.001; 69.9%, P<0.001), and ischaemic heart disease (6.7days, P<0.001; 38.7%, P<0.05). CONCLUSION: CVD risk factors have a significant and varied impact on LOS and mortality in patients with ACS and it may be inappropriate to group them when assessing in-hospital risk. These factors should be used to identify patients at an increased risk of prolonged admissions and death post-ACS, and services should be directed accordingly. PMID- 27393861 TI - Heart failure in Tanzania and Sweden: Comparative characterization and prognosis in the Tanzania Heart Failure (TaHeF) study and the Swedish Heart Failure Registry (SwedeHF). AB - BACKGROUND: Heart failure (HF) in developing countries is poorly described. We compare characteristics and prognosis of HF in Tanzania vs. Sweden. METHODS: A prospective cohort study was conducted from the Tanzania HF study (TaHeF) and the Swedish HF Registry (SwedeHF). Patients were compared overall (n 427 vs. 51,060) and after matching 1:3 by gender and age+/-5years (n 411 vs. 1232). The association between cohort and all-cause mortality was assessed with multivariable Cox regression. RESULTS: In the unmatched cohorts, TaHeF (as compared to SwedeHF) patients were younger (median age [interquartile range] 55 [40-68] vs. 77 [64-84] years, p<0.001) and more commonly women (51% vs. 40%, p<0.001). The three-year survival was 61% in both cohorts. In the matched cohorts, TaHeF patients had more hypertension (47% vs. 37%, p<0.001), more anemia (57% vs. 9%), more preserved EF, more advanced HF, longer duration of HF, and less use of beta-blockers. Crude mortality was worse in TaHeF (HR 2.25 [95% CI 1.78-2.85], p<0.001), with three-year survival 61% vs. 83%. However, covariate adjusted risk was similar (HR 1.07, 95% CI 0.69-1.66; p=0.760). In both cohorts, preserved EF was associated with higher mortality in crude but not adjusted analysis. CONCLUSIONS: Compared to in Sweden, HF patients in Tanzania were younger and more commonly female, and after age and gender matching, had more frequent hypertension and anemia, more severe HF despite higher EF, and worse crude but similar adjusted prognosis. PMID- 27393862 TI - Letter by Cornelis et al. regarding article, "Exercise oscillatory ventilation in heart failure". PMID- 27393863 TI - Invasive strategy in non-ST-segment elevation acute coronary syndrome: What should be the benchmark target in the real world patients? Insights from BLITZ-4 Quality Campaign. AB - AIMS: To define a benchmark target for an invasive strategy (IS) rate appropriate for performance assessment in intermediate-to-high risk non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: During the BLITZ-4 campaign, which aimed at improving the quality of care in 163 Italian coronary care units, 4923/5786 (85.1%) of consecutive patients admitted with NSTE-ACS with troponin elevation and/or dynamic ST-T changes on the electrocardiogram were managed with IS. The reasons driving the choice (RDC) for a conservative strategy (CS) in the remaining 863 patients were prospectively recorded. In 33.8%, CS was mandatory because of patients refusal, known coronary anatomy or death before coronary angiography; in 52.8% it was clinically justified because of active stroke, bleeding, advanced frailty, severe comorbidities, contraindication to antiplatelet therapy or because they were considered to be at low risk; only in 13.4% the reasons, such as renal failure, advanced age or other, were less stringent. As compared to patients undergoing IS, those in the CS were 12years older and had significantly more severe comorbidities. The in-hospital and 6 month all-cause mortality were 9.0% vs 0.9% and 22.0% vs 3.9% in CS and IS groups respectively (p<0.0001 for both). CONCLUSION: As the RDC for CS were clinically correct in vast majority of cases the observed 85% invasive strategy rate may be considered as the desirable benchmark target in patients with NSTE-ACS. For the same reason, it remains questionable if the higher rate of IS could have improved the prognosis in CS patients, despite their highly unfavorable prognosis. PMID- 27393864 TI - Cataract increases the risk of peripheral artery occlusive disease: A nationwide population-based cohort study with propensity score. AB - PURPOSE: We conducted this study to evaluate the risk of peripheral artery occlusive disease (PAOD) among patients with cataracts. METHODS: We analyzed the data from Taiwan National Health Insurance Research Database. Study participants were classified into the cataract group and the non-cataract group between 2000 and 2010. All patients were observed from the index year until PAOD diagnosis, loss to follow up, or the end of 2011. Both study groups were 1:1 matching based upon a propensity score. We used a cox proportional hazards regression model to assess the hazard ratio (HR) and 95% confidence interval (CI) of PAOD for the cataract cohort compared with the non-cataract cohort. RESULTS: After adjustment for age, sex and comorbidities, the risk of PAOD was significantly higher in the cataract cohort [adjusted HR (aHR)=1.48, 95% CI=1.38-1.58] than the non-cataract cohort. CONCLUSIONS: We found that patients with cataracts had a 1.48-fold increased risk of developing PAOD compared to the non-cataract patients. PMID- 27393865 TI - Personalised External Aortic Root Support (PEARS): Utilisation in dilatational aortopathies after the arterial switch operation V4. PMID- 27393866 TI - Digit ratio (2D:4D), testosterone, cortisol, aggression, personality and hand grip strength: Evidence for prenatal effects on strength. AB - BACKGROUND: Digit ratio (2D:4D) is a putative marker for prenatal testosterone and is correlated with performance in many sports. Low 2D:4D has been linked to strength but the evidence is mixed and strength is also influenced by mass, testosterone, and behavioural factors. It has been hypothesised that the 2D:4D strength correlation may be strongest in challenge conditions when short-term changes occur in steroid hormones. AIMS: We tested this suggestion in men. STUDY DESIGN: We used a cross-over study design with a challenge (an aggressive video of rugby tackles) and control (a blank screen) condition. SUBJECTS: 89 healthy men. OUTCOME MEASURES: Finger lengths (2nd and 4th for both hands), hand-grip strength (HGS), testosterone (T), cortisol (C), aggression (Buss-Perry Aggression Questionnaire) and personality type (Ten Item Personality Measure). In both conditions participants provided saliva samples (for hormone assays). RESULTS: In the challenge condition there was a highly significant increase in HGS, and modest changes in T, physical aggression and emotional stability. HGS correlated negatively with left hand 2D:4D. In a multiple regression, left hand 2D:4D was negatively related to HGS and emotional stability was positively related to HGS. In the control condition HGS was not correlated with 2D:4D. In a multiple regression, BMI, physical aggression, and emotional stability were significantly related to HGS. CONCLUSIONS: 2D:4D is a negative correlate of strength in challenge situations. This finding may in part explain associations between 2D:4D and sports performance. PMID- 27393867 TI - Human sex ratio at birth after atmospheric weapons testing. PMID- 27393868 TI - Infant mortality at term in Canada: Impact of week of gestation. AB - OBJECTIVES: Infants born at term have low mortality, but risk may vary from week to week. We determined the risk of infant mortality at term by gestational week and cause. METHODS: We analyzed 4.1 million infants born at >=37weeks of gestation in Canada from 1991 to 2010, followed for mortality the first year of life. We estimated hazard ratios (HR) and 95% CIs for early, late and post neonatal mortality from 37 through 41weeks of gestation, adjusting for individual characteristics. The main outcomes were mortality due to congenital anomaly, asphyxia, immaturity, infection, sudden infant death, and injury. RESULTS: Infant mortality decreased progressively from 4.55 per 1000 at 37weeks to 1.62 per 1000 at 41weeks. Early neonatal mortality varied little between 39 and 41weeks, but post neonatal mortality was lowest at 40-41weeks. Relative to 41weeks of gestation, mortality at 39weeks was higher for congenital anomaly (HR 1.30, 95% CI 1.05-1.60) and sudden infant death (HR 1.58, 95% CI 1.18-2.11). CONCLUSION: In Canada, mortality at term is lowest for infants born at 40 or 41weeks of gestation, especially at late and post neonatal ages, and for congenital anomaly and sudden infant death. PMID- 27393870 TI - Context-dependency in valuation. AB - In the last few years, work in the nascent field of neuroeconomics has advanced understanding of the brain systems involved in value-based decision making. An important modulator of valuation processes is the specific context a decision maker is facing during choice. Recently, neuroeconomics has made great progress in understanding, on both the brain and behavioral level, how context-dependent perception affects valuation and choice. Here we describe how context-sensitive value coding accounts for choice set effects, differential perceptions of gains and losses, and expectancy effects of external (economic) signals. PMID- 27393871 TI - WAHIS-Wild and its interface: the OIE worldwide monitoring system for wild animal diseases. AB - Wild animal diseases are a global growing concern, given the threat that they pose to animal health and their zoonotic potential. The World Organisation for Animal Health (OIE) was among the first organisations to recognise the importance of having a comprehensive knowledge of the disease situation in wild animals, collecting information on wildlife diseases worldwide since 1993, when for the first time an annual questionnaire was distribute by OIE to members Countries in order to collect qualitative and quantitative data on selected diseases in wild animals. Starting with 2008 until 2012 an updated version of questionnaire was circulated to allow for identifying wildlife species by their Latin name and by their common names in the 3 OIE official languages (English, French, and Spanish). This specific functionality was then implemented in the World Animal Health Information System (WAHIS) in 2012, when this information was made available to the public through WAHIS-Wild Interface. PMID- 27393869 TI - The good, the bad, and the hungry: how the central brain codes odor valence to facilitate food approach in Drosophila. AB - All animals must eat in order to survive but first they must successfully locate and appraise food resources in a manner consonant with their needs. To accomplish this, external sensory information, in particular olfactory food cues, need to be detected and appropriately categorized. Recent advances in Drosophila point to the existence of parallel processing circuits within the central brain that encode odor valence, supporting approach and avoidance behaviors. Strikingly, many elements within these neural systems are subject to modification as a function of the fly's satiety state. In this review we describe those advances and their potential impact on the decision to feed. PMID- 27393872 TI - Preliminary results on innocuity and immunogenicity of an inactivated vaccine against Peste des petits ruminants. AB - Peste des petits ruminants (PPR) virus belongs to the family Paramyxoviridae and represents a major threat to small livestock industry. In recent years, outbreaks of PPR have occurred in Turkey and North Africa. In endemic areas, disease prevention is accomplished using live-attenuated vaccines. However, the use of live vaccines in non-endemic regions, such as Europe, is not approved by Veterinary Authorities. In these regions inactivated vaccines are then the only viable alternative. In this study an inactivated vaccine (iPPRVac) was formulated with either a water-in-oil emulsion (ISA 71 VG) or with delta inulin adjuvant, alone (AFSA1) or combined with a TLR9 agonist oligonucleotide (AFSA2). These formulations were then tested for immunogenicity on rats. The iPPRV formulation with AFSA2 adjuvant induced 100% seroconversion in rats after 2 injections and was subsequently evaluated in goats. Five goats were immunised twice subcutaneously, 36 days apart with iPPRVac + AFSA2. The immunised goats all seroconverted to PPR by day 9 and remained seropositive until the end of the experimental period (133 days). These data indicate that the rat model is useful in predicting vaccine responses in goats and that inactivated vaccine, when formulated with a delta inulin adjuvant, represents a promising alternative to live attenuated vaccines for PPR vaccination campaigns in non-endemic areas. PMID- 27393873 TI - Prevalence of hydatidosis and fertility of hydatid cysts in food animals in Northern Greece. AB - This study was conducted in order to determine the prevalence of hydatidosis due to Echinococcus granulosus sensu lato and the fertility rate of hydatid cysts in sheep, goats, cattle, and pigs slaughtered at the abattoir of Lagkada, in the Prefecture of Thessaloniki, Northern Greece. Lungs and livers from a total of 294 sheep (31.3% infected), 126 goats (8.7% infected), 372 cattle (4.8% infected), and 641 pigs (1.7% infected) were examined. The number of hydatid cysts found in infected sheep was 657 (58.3% fertile, 12.8% sterile, and 28.9% calcified cysts), in goats 54 (14.8% fertile, 38.9% sterile, and 46.3% calcified cysts), in cattle 108 (24.1% fertile, 50.0% sterile, and 25.9% calcified cysts) and in pigs 47 (10.6% fertile, 55.4% sterile, and 34.0% calcified cysts). Lung infection with hydatid cysts was higher (p<0.05) in sheep, goats, and cattle than in pigs (56.5%, 77.8% and 62.0% vs. 17.0%, respectively); while liver infection was lower (p<0.05) in sheep, goats, and cattle than in pigs (43.5%, 22.2% and 38.0% vs. 83.0%, respectively). Among the 4 species slaughtered for human consumption, sheep exhibited the highest frequency of hydatidosis and the highest proportion of fertile cysts. PMID- 27393874 TI - Serological surveillance of Leptospirosis in Italy: two-year national data (2010 2011). AB - Nowadays, leptospirosis is a re-emerging widespread infectious disease often underestimate worldwide. The National Reference Centre for Leptospirosis (NRCL), at the Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Brescia (Italy), with the cooperation of all the other Istituti Zooprofilattici Sperimentali (IIZZSS), evaluated the distribution of such important zoonosis in Italy. Serological data obtained between 2010-2011 by each laboratory were collected by the NRCL and discussed. Serum samples collected from 43,935 animal specimens were analysed by the Microscopic Agglutination Test (MAT), using a panel of 8 serogroups as antigens (Australis, Ballum, Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona, Sejroe, Tarassovi). A MAT cut-off of 1:100 was used to identify the serological positivities, 6,279 sera showed positive titers. Bovine (46.9%), swine (27.5%), ovine and goat (7.4%), dog (6.9%), and wild boar (4.5%) samples were delivered to the Laboratories more frequently than equine and other species sera. Data analysis showed that the most common serogroups in Italy are: Australis present in dogs, wild boars, horses, hares, swine, foxes, and rodents; Sejroe detected in cattle, sheep, goats, and buffaloes; Icterohaemorrhagiae present in dogs, goats, and foxes; Pomona detected in swine, cattle, and wild species; Grippotyphosa reported in hares. PMID- 27393875 TI - Antimicrobial resistance patterns of Enterobacteriaceae in European wild bird species admitted in a wildlife rescue centre. AB - Wild birds have been considered to be reservoirs of enteric human pathogens and vectors of resistance dissemination to the environment. During annual migration, they potentially play a role in the epidemiology of human associated zoonoses. The aim of this study was to investigate the frequency of isolation and antimicrobial susceptibility profiles of Enterobacteriaceae members isolated from cloacal swabs of common European wild birds. Fifty-five cloacal swabs were taken during birds' entrance evaluation in a rescue centre for injured wild birds in the Province of Messina (Sicily, Italy). All samples were examined for the presence of members of the family Enterobacteriaceae using standard methods and on the isolated strains antibiotic susceptibility testing was performed. Eighty three Enterobacteriaceae strains were isolated from raptors, waterbirds and passerines. The bacterial species isolated were: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Salmonella Typhimurium, Escherichia vulneris, Enterobacter amnigenus biogroup 2, Salmonella Duesseldorf and Hafnia alvei. The isolates showed significant frequencies of antibiotic resistance. Multiresistance to three or more groups of antibiotics also occurred. None of them have shown a phenotypic Extended Spectrum Beta Lactamase (ESBL) profile. PMID- 27393876 TI - Fumagillin control of Nosema ceranae (Microsporidia:Nosematidae) infection in honey bee (Hymenoptera:Apidae) colonies in Argentina. AB - Information on the long-term consequences of Nosema ceranae to honey bee lifespan and effectiveness of Nosema control with fumagillin is scarce and not always consistent. Our objective in this study was to evaluate the effectiveness of the antibiotic fumagillin to control N. ceranae in hives in East-Central Argentina. Honey bee hives were assigned to 3 experimental treatments, a control group with un-treated hives, a preventive strategy group with hives treated monthly, and a monitoring strategy group with hives treated according to a N. ceranae threshold level. Apiaries were monitored monthly during Fall-Winter 2009 and 2010 and N. ceranae spore intensity and honey bee colony strength measures were estimated. Fumagillin-treated colonies had reduced N. ceranae spores load in 2010 compared to control colonies. However, there was no significant difference between treated and control groups for colony strength measures including adult bee population, bee brood availability, honey, or pollen. Fumagillin treatment reduced N. ceranae intensities but had little effect on colonies. The bee population during Winter was reduced in treated as well as in control colonies. Our results clarify that fumagillin treatment should be at least reviewed and that further research should be conducted to acquire a more complete perspective of Nosemosis disease. PMID- 27393877 TI - Anticoagulant rodenticide poisoning in animals of Apulia and Basilicata, Italy. AB - This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high-performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice. PMID- 27393878 TI - The Arbo-zoonet Information System. AB - The Arbo-zoonet Information System has been developed as part of the 'International Network for Capacity Building for the Control of Emerging Viral Vector Borne Zoonotic Diseases (Arbo-zoonet)' project. The project aims to create common knowledge, sharing data, expertise, experiences, and scientific information on West Nile Disease (WND), Crimean-Congo haemorrhagic fever (CCHF), and Rift Valley fever (RVF). These arthropod-borne diseases of domestic and wild animals can affect humans, posing great threat to public health. Since November 2011, when the Schmallenberg virus (SBV) has been discovered for the first time in Northern Europe, the Arbo-zoonet Information System has been used in order to collect information on newly discovered disease and to manage the epidemic emergency. The system monitors the geographical distribution and epidemiological evolution of CCHF, RVF, and WND since 1946. More recently, it has also been deployed to monitor the SBV data. The Arbo-zoonet Information System includes a web application for the management of the database in which data are stored and a WebGIS application to explore spatial disease distributions, facilitating the epidemiological analysis. The WebGIS application is an effective tool to show and share the information and to facilitate the exchange and dissemination of relevant data among project's participants. PMID- 27393879 TI - Lack of detection of West Nile virus in an islander population of chelonians during a West Nile virus outbreak. AB - In 2011, several outbreaks of West Nile disease occurred in Sardinia (Italy). The region hosts several chelonian species. Because of the increasing concern on the potential role that ectotherms may play in the ecology of West Nile virus (WNV), in October 2011 blood samples were collected from 41 endemic Sardinian chelonians and tested for the presence of active WNV infection or neutralizing antibodies by real time polymerase chain reaction (RT-PCR) and serumneutralisation, respectively. Neither WNV neutralising antibodies (0%; 95% CI: 0-8.4%) nor WNV RNA (0%; 95% CI: 0-6.8%) were found in the tested samples. According to the results of this screening survey, it is unlikely that chelonians are involved in the epidemiology of the 2011 WNV outbreaks in Sardinia. PMID- 27393880 TI - Online Educational Video Improves Bowel Preparation and Reduces the Need for Repeat Colonoscopy Within Three Years. AB - PURPOSE: Unsatisfactory bowel preparation has been reported in up to 33% of screening colonoscopies. Patients' lack of understanding about how a good bowel preparation can be achieved is one of the major causes. Patient education has been explored as a possible intervention to improve this important endpoint and has yielded mixed results. We compared the proportion of satisfactory bowel preparations and adenoma detection rates between patients who viewed and did not view an educational video on colonoscopy. METHODS: An educational video on colonoscopy, accessible via the Internet, was issued to all patients with planned procedures between 2010 and 2014. Viewing status of the video was verified through a unique code linked to each patient's medical record. Excellent, good, or adequate bowel preparations were defined as "satisfactory," whereas fair, poor, or inadequate bowel preparations were defined as "unsatisfactory." RESULTS: A total of 2530 patients undergoing their first outpatient screening colonoscopy were included; 1251 patients viewed the educational video and 1279 patients did not see the video. Multivariate analysis revealed higher rates of satisfactory bowel preparation in the educational video group (92.3% [95% confidence interval [CI], 84.8-96.3] vs 87.4% [95% CI, 76.4-93.7], P <.001). Need for a repeat colonoscopy within 3 years was also higher in patients who did not see the video (6.6% [95% CI, 2.8-14.7] vs 3.3% [95% CI 1.3-7.8], P <.001). CONCLUSION: Patient centered educational video improves bowel preparation quality and may reduce the need for an earlier repeat procedure in patients undergoing screening colonoscopy. PMID- 27393881 TI - Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study. AB - BACKGROUND: Clinic-based studies have indicated that older hypothyroid patients may present only few symptoms. METHODS: In this population-based study of hypothyroidism, we investigated how the power of symptom presence predicts overt hypothyroidism in both young and older subjects. We identified patients newly diagnosed with overt autoimmune hypothyroidism in a population (n = 140, median thyroid-stimulating hormone, 54.5; 95% confidence interval [CI], 28.3-94.8; median total T4, 37; 95% CI, 18-52) and individually matched each patient with 4 controls free of thyroid disease (n = 560). Participants filled out questionnaires concerning the presence and duration of symptoms. We compared the usefulness of hypothyroidism-associated symptoms in predicting overt hypothyroidism in different age groups (young: <50 years, middle age: 50-59 years, old: >=60 years) also taking various confounders into account. RESULTS: In young hypothyroid patients, all 13 hypothyroidism-associated symptoms studied were more prevalent than in their matched controls, whereas only 3 of those (tiredness, shortness of breath, and wheezing) were more prevalent in old patients. The mean numbers of symptoms presented at disease onset were 6.2, 5.0, and 3.6 at the ages of 0 to 49 years, 50 to 59 years, and 60+ years, respectively. In young versus old people with 0 to 1 symptoms, the odds ratio for being hypothyroid was 0.04 (95% CI, 0.007-0.18) versus 0.34 (95% CI, 0.15-0.78) (reference all other groups). In young versus old subjects reporting >=4 symptoms, the odds ratio for being hypothyroid was 16.4 (95% CI, 6.96-40.0) versus 2.22 (95% CI, 1.001-4.90). Receiver operating characteristic analyses revealed that the symptom score was an excellent tool for predicting hypothyroidism in young men (area under the receiver operating characteristic curve, 0.91; 95% CI, 0.82-0.998), whereas it was poor in evaluating older women (area under the receiver operating characteristic curve, 0.64; 95% CI, 0.54 0.75). CONCLUSION: Hypothyroid symptom score is a good discriminating tool to identify hypothyroidism in young patients but fails to identify hypothyroidism in the elderly. Thus, thyroid function should be tested on wide indications in old age. PMID- 27393882 TI - A Silent Relic: Uremic Pericardial Effusion. PMID- 27393883 TI - The Pretender: Pulmonary Embolism. PMID- 27393884 TI - Incidence and growth of Salmonella enterica on the peel and pulp of avocado (Persea americana) and custard apple (Annona squamosa). AB - The aim of this study was to assess the incidence and to estimate the growth kinetic parameters (maximum growth rate, MU; lag time, lambda; and maximum population, kappa) of Salmonella on the peel and pulp of avocado (Perseaamericana var. americana) and custard apple (Annona squamosa L.) as affected by temperature (10-30 degrees C). The incidence of Salmonella was assessed on the peel and pulp of the fruits (n=200 of each fruit), separately, totalizing 800 analyses. Only three samples of custard apple pulp were positive for Salmonella enterica and the three isolates recovered belonged to serotype S. Typhimurium. Salmonella was not recovered from avocado and custard apple peels and from avocado pulp. Generally, the substrate (pulp or peel) of growth did not affect MU values of S. enterica (p>0.05). Very similar MU values were found for S. enterica inoculated in custard apple and avocado. S. enterica presented the highest lambda in the peel of the fruits. The growth of S. enterica resulted in larger lambda in custard apple in comparison to avocado. For example, the lambda of S. enterica in the pulp of custard apple and avocado were 47.0+/-0.78h and 10.0+/-3.78h, respectively. The lowest values of kappa were obtained at the lower storage temperature conditions (10 degrees C). For instance, kappa values of 3.7+/-0.06log CFU/g and 2.9+/ 0.03log CFU/g were obtained from the growth of S. enterica in avocado and custard apple pulps at 10 degrees C (p<0.05), respectively. On the other hand, at 30 degrees C, kappa values were 6.5+/-0.25log CFU/g and 6.5+/-0.05log CFU/g, respectively. Significantly higher kappa were obtained from the growth of S. enterica in the pulp than in the peel of the fruits (p<0.05). For instance, the growth of S. enterica in the pulp of avocado led to a kappa value of 6.5+/ 0.25log CFU/g, while in the peel led to a kappa value of 4.6+/-0.23log CFU/g (p<0.05). In general, growth kinetic parameters indicated that avocado comprises a better substrate than custard apple for the growth of S. enterica. The square root model fitted to the data obtained in this study and to the growth data available in the literature for other tropical low acid fruits indicated high variability in MU and lambda of Salmonella. The results obtained in this study show that whole low acid tropical fruits can harbor Salmonella, and that this foodborne pathogen can not only survive but also grow both on the peel and pulp of low acid tropical fruits, such as avocado and custard apple. PMID- 27393885 TI - Influence of food intrinsic complexity on Listeria monocytogenes growth in/on vacuum-packed model systems at suboptimal temperatures. AB - Food intrinsic factors e.g., food (micro)structure, compositional and physicochemical aspects, which are mutually dependent, influence microbial growth. While the effect of composition and physicochemical properties on microbial growth has been thoroughly assessed and characterised, the role of food (micro)structure still remains unravelled. Most studies on food (micro)structure focus on comparing planktonic growth in liquid (microbiological) media with colonial growth in/on solid-like systems or on real food surfaces. However, foods are not only liquids or solids; they can also be emulsions or gelled emulsions and have complex compositions. In this study, Listeria monocytogenes growth was studied on the whole spectrum of (micro)structure, in terms of food (model) systems. The model systems varied not only in (micro)structure, which was the target of the study, but also in compositional and physicochemical characteristics, which was an inevitable consequence of the (micro)structural variability. The compositional and physicochemical differences were mainly due to the presence or absence of fat and gelling agents. The targeted (micro)structures were: i) liquids, ii) aqueous gels, iii) emulsions and iv) gelled emulsions. Furthermore, the microbial dynamics were studied and compared in/on all these model systems, as well as on a compositionally predefined canned meat, developed in order to have equal compositional level to the gelled emulsion model system and represent a real food system. Frankfurter sausages were the targeted real foods, selected as a case study, to which the canned meat had similar compositional characteristics. All systems were vacuum packed and incubated at 4, 8 and 12 degrees C. The most appropriate protocol for the preparation of the model systems was developed. The pH, water activity and resistance to penetration of the model systems were characterised. Results indicated that low temperature contributes to growth variations among the model systems. Additionally, the firmer the solid system, the faster L. monocytogenes grew on it. Finally, it was found that L. monocytogenes grows faster on canned meat and real Frankfurters, as found in a previous study, followed by liquids, aqueous gels, emulsions and gelled emulsions. This observation indicates that all model systems, developed in this study, underestimated L. monocytogenes growth. Despite some limitations, model systems are overall advantageous and therefore, their validation is always recommended prior to further use. PMID- 27393886 TI - Synthesis of [diene-(14)C] curcumin at high specific activity. AB - An efficient method is described to label curcumin with (14)C at high specific activity. PMID- 27393887 TI - Thin films of silk fibroin and its blend with chitosan strongly promote biofilm growth of Synechococcus sp. BDU 140432. AB - The activating role of different polymer thin films coated over polystyrene support on the Synechococcus sp. biofilm growth was examined concurrently by measuring biofilm florescence using a dye and by measuring cell density in the isolated biofilm. Compared to blank (no coating), the increase in biofilm formation (%) on silk, chitosan, silk-chitosan (3:2) blend, polyaniline, osmium, and Nafion films were 27.73 (31.16), 21.55 (23.74), 37.21 (38.34), 5.35 (8.96), 6.70 (6.55) and (nil), respectively with corresponding cell density (%) shown in the parentheses. This trend of biofilm formation on the films did not significantly vary for Escherichia coli and Lactobacillus plantarum strains. The films of 20 residues long each of glycine-alanine repeat peptide, which mimics a silk fibroin motif, and a hydrophobic glycine-valine repeat peptide, increased the biofilm growth by 13.53 % and 26.08 %, respectively. Silk and blend films showed highest adhesion unit (0.48-0.49), adhesion rate ((4.2-4.8)*10(-6), m/s) and Gibbs energy of adhesion (-8.5 to -8.6kT) with Synechococcus sp. The results confirmed interplay of electrostatic and hydrophobic interaction between cell surface and polymer films for promoting rapid biofilm growth. This study established that the thin films of silk and the blend (3:2) promote rapid biofilm growth for all the tested microorganisms. PMID- 27393888 TI - Investigation of catalytic activity towards oxygen reduction reaction of Pt dispersed on boron doped graphene in acid medium. AB - Boron doped graphene was prepared by a facile method and platinum (Pt) decoration over boron doped graphene was done in various chemical reduction methods such as sodium borohydride (NaBH4), polyol and modified polyol. X-ray diffraction analysis indicates that the synthesized catalyst particles are present in a nanocrystalline structure and transmission and scanning electron microscopy were employed to investigate the morphology and particle distribution. The electrochemical properties were investigated with the help of the rotating disk electrode (RDE) technique and cyclic voltammetry. The results show that the oxygen reduction reaction (ORR) takes place by a four-electron process. The kinetics of the ORR was evaluated using K-L and Tafel plots. The electrocatalyst obtained in modified polyol reduction method has shown the better catalytic activity compared to other two electrocatalysts. PMID- 27393889 TI - Adsorptional photocatalytic mineralization of oxytetracycline and ampicillin antibiotics using Bi2O3/BiOCl supported on graphene sand composite and chitosan. AB - In present study, heterojunctioned Bi2O3/BiOCl (BO/BOC) was synthesized via in situ chemical reduction and oxidation of BiOCl nanoplates. BiOCl was reduced to metallic Bi in KHB4 solution followed by oxidation in H2O2 solution to produce BO/BOC. The BO/BOC was supported over graphene sand composite and also on chitosan using wet impregnation method to report BO/BOC/GSC and BO/BOC/CT nanocomposite. The morphology and compositional characteristics of BO/BOC/GSC and BO/BOC/CT were investigated by FESEM, TEM, HRTEM, FTIR, XRD, EDX, RAMAN, BET and UV-visible diffuse reflectance spectral analysis. The photocatalytic activity of BO/BOC/GSC and BO/BOC/CT was performed for mineralization of ampicillin (AMP) and oxytetracycline (OTC) antibiotics under solar light. The adsorption process had significant effect on photodegradation of AMP and OTC. The adsorption of both OTC and AMP onto BO/BOC/GSC and BO/BOC/CT followed pseudo second order kinetics. Simultaneous adsorption and degradation process (A+P) resulted in higher degradation rate of investigated antibiotics. The applicability of power law model indicates the intricacies of mineralization process. During A+P process, OTC and AMP were mineralized to CO2.H2O, NO3(-) and SO4(2-) ions. Both BO/BOC/GSC and BO/BOC/CT exhibited significant recycle efficiency. PMID- 27393891 TI - Brief time course of trait anxiety-related attentional bias to fear-conditioned stimuli: Evidence from the dual-RSVP task. AB - BACKGROUND AND OBJECTIVES: Attentional bias to threat is a much-studied feature of anxiety; it is typically assessed using response time (RT) tasks such as the dot probe. Findings regarding the time course of attentional bias have been inconsistent, possibly because RT tasks are sensitive to processes downstream of attention. METHODS: Attentional bias was assessed using an accuracy-based task in which participants detected a single digit in two simultaneous rapid serial visual presentation (RSVP) streams of letters. Before the target, two coloured shapes were presented simultaneously, one in each RSVP stream; one shape had previously been associated with threat through Pavlovian fear conditioning. Attentional bias was indicated wherever participants identified targets in the threat's RSVP stream more accurately than targets in the other RSVP stream. RESULTS: In 87 unselected undergraduates, trait anxiety only predicted attentional bias when the target was presented immediately following the shapes, i.e. 160 ms later; by 320 ms the bias had disappeared. This suggests attentional bias in anxiety can be extremely brief and transitory. LIMITATIONS: This initial study utilised an analogue sample, and was unable to physiologically verify the efficacy of the conditioning. The next steps will be to verify these results in a sample of diagnosed anxious patients, and to use alternative threat stimuli. CONCLUSIONS: The results of studies using response time to assess the time course of attentional bias may partially reflect later processes such as decision making and response preparation. This may limit the efficacy of therapies aiming to retrain attentional biases using response time tasks. PMID- 27393890 TI - Pleiotropic effects of 4-hydroxynonenal on oxidative burst and phagocytosis in neutrophils. AB - Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neutrophil NADPH oxidases consume large quantities of oxygen to rapidly generate ROS, a process that is referred to as the oxidative burst. These ROS are required for the efficient removal of phagocytized cellular debris and pathogens. In chronic inflammatory diseases, neutrophils are exposed to increased levels of oxidants and pro-inflammatory cytokines that can further prime oxidative burst responses and generate lipid oxidation products such as 4 hydroxynonenal (4-HNE). In this study we hypothesized that since 4-HNE can target glycolysis then this could modify the oxidative burst. To address this the oxidative burst was determined in freshly isolated healthy subject neutrophils using 13-phorbol myristate acetate (PMA) and the extracellular flux analyzer. Neutrophils pretreated with 4-HNE exhibited a significant decrease in the oxidative burst response and phagocytosis. Mass spectrometric analysis of alkyne HNE treated neutrophils followed by click chemistry detected modification of a number of cytoskeletal, metabolic, redox and signaling proteins that are critical for the NADPH oxidase mediated oxidative burst. These modifications were confirmed using a candidate immunoblot approach for critical proteins of the active NADPH oxidase enzyme complex (Nox2 gp91phox subunit and Rac1 of the NADPH oxidase) and glyceraldehyde phosphate dehydrogenase, a critical enzyme in the metabolic regulation of oxidative burst. Taken together, these data suggest that 4-HNE-induces a pleiotropic mechanism to inhibit neutrophil function. These mechanisms may contribute to the immune dysregulation associated with chronic pathological conditions where 4-HNE is generated. PMID- 27393892 TI - White matter shifts in MRI: Rehabilitating the Lorentz sphere in magnetic resonance. AB - A thorough exposition and analysis of the role of the Lorentz sphere in magnetic resonance is presented from the fundamental standpoint of macroscopic magnetostatics. The analysis will be useful to those interested in understanding susceptibility and chemical shift contributions to frequency shifts in magnetic resonance. Though the topic is mature, recent research on white matter shifts in the brain promotes the notion of replacing the Lorentz sphere with a generalized Lorentzian cylinder, and has put into question the long standing spherical approach when elongated structures are present. The cavity shape issue can be resolved by applying Helmholtz's theorem, which can be expressed in a differential and an integral formulation. The general validity of the Lorentz sphere for any situation is confirmed. Furthermore, a clear exposition of the "generalized approach" is offered, using the language of Lorentz's theory. With the rehabilitation of the Lorentz sphere settled, one must consider alternative contributions to white matter shifts and a likely candidate is the effect of molecular environment on chemical shifts. PMID- 27393894 TI - Reply by Authors. PMID- 27393893 TI - Improving the long-term stability of Ti6Al4V abutment screw by coating micro/nano crystalline diamond films. AB - Abutment screw loosening is the most common complication of implanting teeth. Aimed at improving the long-term stability of them, well-adherent and homogeneous micro-crystalline diamond (MCD) and nano-crystalline diamond (NCD) were deposited on DIO((r)) (Dong Seo, Korea) abutment screws using a hot filament chemical vapor deposition (HFCVD) system. Compared with bare DIO((r)) screws, diamond coated ones showed higher post reverse toque values than the bare ones (p<0.05) after cyclic loading one million times under 100N, and no obvious flaking happened after loading test. Diamond coated disks showed lower friction coefficients of 0.15 and 0.18 in artificial saliva when countered with ZrO2 than that of bare Ti6Al4V disks of 0.40. Though higher cell apoptosis rate was observed on film coated disks, but no significant difference between MCD group and NCD group. And the cytotoxicity of diamond films was acceptable for the fact that the cell viability of them was still higher than 70% after cultured for 72h. It can be inferred that coating diamond films might be a promising modification method for Ti6Al4V abutment screws. PMID- 27393895 TI - Reply by Authors. PMID- 27393896 TI - Reply by Authors. PMID- 27393897 TI - Reply by Authors. PMID- 27393898 TI - Re: Percutaneous Kidney Biopsy for a Small Renal Mass: A Critical Appraisal of Results: H. G. Jeon, S. I. Seo, B. C. Jeong, S. S. Jeon, H. M. Lee, H. Y. Choi, C. Song, J. H. Hong, C. S. Kim, H. Ahn and I. G. Jeong J Urol 2016;195:568-573. PMID- 27393899 TI - Editorial Comment. PMID- 27393900 TI - Re: A Retrospective Analysis of the Effect on Survival of Time from Diagnosis to Neoadjuvant Chemotherapy to Cystectomy for Muscle Invasive Bladder Cancer: J. C. Park, N. M. Gandhi, M. A. Carducci, M. A. Eisenberger, A. S. Baras, G. J. Netto, J. J. Liu, C. G. Drake, M. P. Schoenberg, T. J. Bivalacqua and N. M. Hahn J Urol 2016;195:880-885. PMID- 27393901 TI - Re: Critical Analysis of Early Recurrence after Laparoscopic Radical Cystectomy in a Large Cohort by the ESUT: S. Albisinni, L. Fossion, M. Oderda, O. M. Aboumarzouk, F. Aoun, T. Tokas, V. Varca, R. Sanchez-Salas, X. Cathelineau, P. Chlosta, F. Gaboardi, U. Nagele, T. Piechaud, J. Rassweiler, P. Rimington, L. Salomon and R. van Velthoven J Urol 2016;195:1710-1717. PMID- 27393903 TI - A two-dimensional model on the coupling thickness-shear vibrations of a quartz crystal resonator loaded by an array spherical-cap viscoelastic material units. AB - We establish a two-dimensional model on the coupling thickness-shear mode (TSM) vibrations of a quartz crystal resonator (QCR) carrying an array of spherical-cap (SC) viscoelastic material units. The electrical admittance of the compound QCR system is described directly in terms of the physical properties of the surface material units. The admittance spectra about the tendon stem cells (TSCs) acquired from our calculation are compared with the existing experiment data and found to be consistent with each other, indicating our model has good veracity and reliability in analyzing the mechanical properties of covered loadings. Furthermore, we calculate admittance spectra of surface Epoxy Resin (SU-8) units with different geometrical configurations and bulk effect. It is found that both geometrical configuration and bulk effect produce influence on the resonant frequency and admittance of the compound QCR system. PMID- 27393902 TI - How does state marijuana policy affect US youth? Medical marijuana laws, marijuana use and perceived harmfulness: 1991-2014. AB - AIMS: To test, among US students: (1) whether perceived harmfulness of marijuana has changed over time, (2) whether perceived harmfulness of marijuana changed post-passage of state medical marijuana laws (MML) compared with pre-passage; and (3) whether perceived harmfulness of marijuana statistically mediates and/or modifies the relation between MML and marijuana use as a function of grade level. DESIGN: Cross-sectional nationally representative surveys of US students, conducted annually, 1991-2014, in the Monitoring the Future study. SETTING: Surveys conducted in schools in all coterminous states; 21 states passed MML between 1996 and 2014. PARTICIPANTS: The sample included 1 134 734 adolescents in 8th, 10th and 12th grades. MEASUREMENTS: State passage of MML; perceived harmfulness of marijuana use (perceiving great or moderate risk to health from smoking marijuana occasionally versus slight or no risk); and marijuana use (prior 30 days). Data were analyzed using time-varying multi-level regression modeling. FINDINGS: The perceived harmfulness of marijuana has decreased significantly since 1991 (from an estimated 84.0% in 1991 to 53.8% in 2014, P < 0.01) and, across time, perceived harmfulness was lower in states that passed MML [odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.97]. In states with MML, perceived harmfulness of marijuana increased among 8th graders after MML passage (OR = 1.21, 95% CI = 1.08-1.36), while marijuana use decreased (OR = 0.81, 95% CI = 0.72-0.92). Results were null for other grades, and for all grades combined. Increases in perceived harmfulness among 8th graders after MML passage was associated with ~33% of the decrease in use. When adolescents were stratified by perceived harmfulness, use in 8th graders decreased to a greater extent among those who perceived marijuana as harmful. CONCLUSIONS: While perceived harmfulness of marijuana use appears to be decreasing nationally among adolescents in the United States, the passage of medical marijuana laws (MML) is associated with increases in perceived harmfulness among young adolescents and marijuana use has decreased among those who perceive marijuana to be harmful after passage of MML. PMID- 27393904 TI - Development and Validation of a Template-Independent Next-Generation Sequencing Assay for Detecting Low-Level Resistance-Associated Variants of Hepatitis C Virus. AB - To develop hepatitis C virus (HCV) direct-acting antiviral (DAA) drugs that can treat most HCV genotypes and offer higher barriers for treatment-resistant mutations, it is important to study resistance-associated variants (RAVs). Current commercially available RAV detection assays rely on genotype- or subtype specific template-dependent PCR amplification. These assays are limited to genotypes and subtypes that are often prevalent in developed countries because of availability of public sequence databases. To support global clinical trials of DAAs, we developed and validated a template-independent (TI) next-generation sequencing (NGS) assay for HCV whole genome sequencing that can perform HCV subtyping, detect HCV mixed genotype or subtype infection, and identify low-level RAVs at a 5% fraction of the viral population with sensitivity and positive predictive value >= 0.9. We compared TI-NGS with commercial genotype- or subtype specific Sanger sequencing assays, and found that TI-NGS both confirmed most of variants called by Sanger sequencing and avoided biases likely caused by PCR primers used in Sanger sequencing. To confirm TI-NGS assay's variant calls at the discrepant positions with Sanger sequencing, we custom designed template dependent NGS assays and obtained 100% concordance with the TI-NGS assay. The ability to reliably detect low-level RAVs in HCV samples of any subtype without PCR primer-related bias makes this TI-NGS assay an important tool in studying HCV DAA drug resistance. PMID- 27393905 TI - Paediatric cancer survivors demonstrate a high rate of subclinical renal dysfunction. AB - BACKGROUND: Clinical manifestations of renal dysfunction in childhood cancer survivors include hypertension, proteinuria, tubulopathy (and its biochemical consequences) and renal insufficiency. This study aimed to determine the factors associated with renal dysfunction in paediatric cancer survivors at a single centre in Johannesburg. PROCEDURE: A descriptive cross-sectional study was performed on 130 cancer survivors between 2 and 18 years of age. Physical examination and screening urine dipstick were performed on all patients. Blood results of samples routinely drawn were analysed. RESULTS: After a median follow up period of 2 years, the various manifestations of renal dysfunction included decreased estimated glomerular filtration rate (eGFR), hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment. The most prevalent manifestation of renal dysfunction was decreased eGFR (17.7%) followed by hypomagnesaemia (6.2%) and hypophosphataemia (4.6%). Patients with pre-existing renal dysfunction were three times more likely to have renal dysfunction post-treatment (P = 0.020). Ifosfamide (P = 0.010) and nephrectomy (P = 0.003) had independent significant impact on reduction in eGFR. High cumulative ifosfamide doses were identified as a possible cause for hypophosphataemia (P = 0.021). CONCLUSION: While not clinically evident in the early follow-up period, the high rate of renal dysfunction is concerning. We suggest that patients with pre-existing renal dysfunction should be assessed by a nephrologist prior to initiation of cancer therapy, and nephro-protective measures should be employed stringently in all children with cancer. Patients with decreased eGFR should be followed up closely in a multidisciplinary late effects clinic. PMID- 27393906 TI - The stress-reducing effect of music listening varies depending on the social context. AB - OBJECTIVE: Given that music listening often occurs in a social context, and given that social support can be associated with a stress-reducing effect, it was tested whether the mere presence of others while listening to music enhances the stress-reducing effect of listening to music. METHODS: A total of 53 participants responded to questions on stress, presence of others, and music listening five times per day (30min after awakening, 1100h, 1400h, 1800h, 2100h) for seven consecutive days. After each assessment, participants were asked to collect a saliva sample for the later analysis of salivary cortisol (as a marker for the hypothalamic-pituitary-adrenal axis) and salivary alpha-amylase (as a marker for the autonomic nervous system). RESULTS: Hierarchical linear modeling revealed that music listening per se was not associated with a stress-reducing effect. However, listening to music in the presence of others led to decreased subjective stress levels, attenuated secretion of salivary cortisol, and higher activity of salivary alpha-amylase. When listening to music alone, music that was listened to for the reason of relaxation predicted lower subjective stress. CONCLUSION: The stress-reducing effect of music listening in daily life varies depending on the presence of others. Music listening in the presence of others enhanced the stress reducing effect of music listening independently of reasons for music listening. Solitary music listening was stress-reducing when relaxation was stated as the reason for music listening. Thus, in daily life, music listening can be used for stress reduction purposes, with the greatest success when it occurs in the presence of others or when it is deliberately listened to for the reason of relaxation. PMID- 27393908 TI - Increased rates of body dissatisfaction, depressive symptoms, and suicide attempts in Jamaican teens with sickle cell disease. AB - BACKGROUND: This study aims to examine the association of body image and weight perceptions with risk of depression and suicidal attempts in Jamaican adolescents with sickle cell disease (SCD). METHODS: Adolescents with SCD and a national sample of Jamaican adolescents completed a questionnaire examining body image, weight perceptions, and risk for depression. RESULTS: Perceived and desired body images were similar for both groups. Adolescents with SCD had higher levels of "negative body satisfaction" (43.9% vs. 33.9%; P = 0.03), risk for depression (28.7% vs. 19.3%; P = 0.01), and attempted suicide (12.4% vs. 6.6%; P = 0.02) than national sample. Risk of depression was higher in those who perceived themselves to be over or underweight, and lower in those with more friends and attending school. Females and those with body image dissatisfaction were more likely to have attempted suicide. Within the SCD adolescents, girls were at greater odds of having mental health issues. CONCLUSIONS: Jamaican adolescents with SCD have significantly higher rates of negative body satisfaction and depressive symptoms, and nearly twice the rate of attempted suicide, compared with their healthy peers. This underscores the need for healthcare professionals to better explore and discuss healthy weight, body satisfaction, and coping with the demands and uncertainties of having a chronic illness with Jamaican adolescents with SCD, even while promoting body acceptance and good self-esteem. Screening for mood disorders is strongly recommended and gender-specific interventions should be developed. Healthcare professionals need to encourage positive social interactions that improve adolescents' mental health. PMID- 27393907 TI - Antenatal glucocorticoid treatment is associated with diurnal cortisol regulation in term-born children. AB - Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus. The synthetic glucocorticoid, betamethasone, is routinely given prenatally to mothers at risk for preterm delivery. Over 25% of the fetuses exposed to betamethasone will be born at term. Few studies have examined the lasting consequences of antenatal treatment of betamethasone on the regulation of the hypothalamic pituitary-adrenal (HPA) axis. The purpose of this study is to examine whether antenatal exposure to betamethasone alters circadian cortisol regulation in children who were born full term. School-aged children prenatally treated with betamethasone and born at term (n=19, mean (SD)=8.1 (1.2) years old) were compared to children not treated with antenatal glucocorticoids (n=61, mean (SD)=8.2 (1.4) years old). To measure the circadian release of cortisol, saliva samples were collected at awakening; 30, 45, and 60min after awakening; and in the evening. Comparison children showed a typical diurnal cortisol pattern that peaked in the morning (the cortisol awakening response) and gradually decreased throughout the day. In contrast, children exposed to antenatal betamethasone lacked a cortisol awakening response and had a flatter diurnal slope (p's<0.01). These data suggest that antenatal glucocorticoid treatment may disrupt the circadian regulation of the HPA axis among children born at term. Because disrupted circadian regulation of cortisol has been linked to mental and somatic health problems, future research is needed to determine whether children exposed to antenatal synthetic glucocorticoids are at risk for poor mental and physical health. PMID- 27393909 TI - Direct and rapid quantitation of ephedrines in human urine by paper spray ionization/high resolution mass spectrometry. AB - A rapid and direct paper spray ionization/mass spectrometry (PSI/MS) method was developed for quantitative analysis of ephedrine, pseudoephedrine, norpseudoephedrine, and methylephedrine in human urine. This method involves the use of a triangular filter paper and high-resolution mass spectrometry, where the molecular ions of ephedrines were generated by applying high voltage after loading the spray solvent to the paper which urine sample was pre-loaded. Small amounts (2MUL) of urine spiked with an internal standard were directly analyzed for ephedrines. The PSI/MS method was validated for linearity, within- and between-run precision, accuracy, and limit of detection. The results showed good linearity (R(2)>=0.9928) and acceptable precision and accuracy. Furthermore, the accuracy of the method was assessed by analyzing a blind urine sample from World Anti-Doping Agency and comparing the measured concentrations with the nominal concentrations. This test resulted in accuracies ranging from 96.4 to 106.1%, indicating that the PSI/MS method has the potential to be an alternative technique for the fast quantitation of ephedrines in doping control analysis. PMID- 27393910 TI - NLRX1 attenuates apoptosis and inflammatory responses in myocardial ischemia by inhibiting MAVS-dependent NLRP3 inflammasome activation. AB - Increasing evidence suggests that inflammation and apoptosis are involved in the development of acute myocardial ischemia (AMI). Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) have recently been identified as key mediators of inflammatory responses. The aim of this study was to explore the specific role and the underlying regulatory mechanism of NLRX1 in myocardial ischemic injury. The results show that NLRX1, located in mitochondria, was significantly down-regulated in AMI tissues and hypoxia-induced H9c2 cells. Overexpression of NLRX1 markedly decreased the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I), down-regulated the production of IL-1beta,IL-18 and IL-6, and reduced apoptosis induced by hypoxia. Conversely, depletion of NLRX1 with small interfering RNA (siRNA) aggravated hypoxia-induced ischemic injury. We then demonstrated that NLRX1 was associated with the mitochondrial antiviral signaling protein (MAVS) and regulated MAVS-dependent NLRP3 inflammasome activation. NLRX1 overexpression significantly inhibited hypoxia-induced up-regulation of MAVS, NLRP3 and Caspase 1 expression. Additionally, the negative effects of NLRX1 overexpression on hypoxia-induced inflammatory factor production and apoptosis were neutralized by MAVS or NLRP3 overexpression. Taken together, these findings suggest that NLRX1 may function as a cardiac-protective molecule in myocardial ischemic injury by repressing inflammation and apoptosis; the biological effects appear to be mediated by the inhibition of MAVS-dependent NLRP3 inflammasome activation. PMID- 27393911 TI - Upregulation of Leukocytic Syncytin-1 in Acute Myeloid Leukemia Patients. AB - BACKGROUND Syncytin-1, a cell membrane-localizing fusogen, is abnormally expressed in several cancers, including endometrial cancer, breast cancer, and leukemia. Although abnormal syncytin-1 expression has been detected in two-thirds of leukemia blood samples, its expression profile in acute leukemia patients has not yet been analyzed. MATERIAL AND METHODS Bone marrow samples from 50 acute myelogenous leukemia (AML) cases and 14 B-cell acute lymphocytic leukemia (B-cell ALL) patients were subjected to flow cytometry to assess leukocyte type distributions and leukocytic syncytin-1 surface expression. RT-PCR was applied to assess leukocytic syncytin-1 mRNA expression. Statistical analysis was applied to compare syncytin-1 expression between AML and B-cell ALL patients across blasts, granulocytes, lymphocytes, and monocytes as well as to determine clinical factors statistically associated with changes in syncytin-1 expression. RESULTS The leukocyte type distributions of the AML and B-cell ALL cohorts highly overlapped, with an observable difference in blast distribution between the 2 cohorts. The AML cohort displayed significantly greater syncytin-1 surface and mRNA expression (p<0.05). Syncytin-1 surface and mRNA expression was significantly increased across all 4 leukocyte types (p<0.05). The percentage of syncytin-1-expressing blasts was significantly greater in AML patients (p<0.05), with blasts showing the largest fold-change in syncytin-1 expression (p<0.05). M5, M5a, and M5b AML patients displayed significantly higher syncytin-1 surface expression relative to all other AML French-American-British (FAB) classifications (p<0.05). CONCLUSIONS These findings suggest leukocytic syncytin-1 expression may play a role in the development and/or maintenance of the AML phenotype and the acute monocytic leukemia phenotype in particular. PMID- 27393912 TI - Development and validation of a generic finite element vehicle buck model for the analysis of driver rib fractures in real life nearside oblique frontal crashes. AB - OBJECTIVE: Frontal crashes still account for approximately half of all fatalities in passenger cars, despite several decades of crash-related research. For serious injuries in this crash mode, several authors have listed the thorax as the most important. Computer simulation provides an effective tool to study crashes and evaluate injury mechanisms, and using stochastic input data, whole populations of crashes can be studied. The aim of this study was to develop a generic buck model and to validate this model on a population of real-life frontal crashes in terms of the risk of rib fracture. METHOD: The study was conducted in four phases. In the first phase, real-life validation data were derived by analyzing NASS/CDS data to find the relationship between injury risk and crash parameters. In addition, available statistical distributions for the parameters were collected. In the second phase, a generic parameterized finite element (FE) model of a vehicle interior was developed based on laser scans from the A2MAC1 database. In the third phase, model parameters that could not be found in the literature were estimated using reverse engineering based on NCAP tests. Finally, in the fourth phase, the stochastic FE model was used to simulate a population of real-life crashes, and the result was compared to the validation data from phase one. RESULTS: The stochastic FE simulation model overestimates the risk of rib fracture, more for young occupants and less for senior occupants. However, if the effect of underestimation of rib fractures in the NASS/CDS material is accounted for using statistical simulations, the risk of rib fracture based on the stochastic FE model matches the risk based on the NASS/CDS data for senior occupants. CONCLUSION: The current version of the stochastic model can be used to evaluate new safety measures using a population of frontal crashes for senior occupants. PMID- 27393913 TI - Understand after like, viewer's delight? A fNIRS study of order-effect in combined hedonic and cognitive appraisal of art. AB - We investigate neural and behavioral aspects of the interrelation between 'liking' and 'understanding' when both appraisals are made within one judgment task. Our goal was to explore questions regarding how these appraisals combine, and specifically whether there is an order-effect when both are employed in sequence. To this end, we tested a hypothesis derived from new models in neuroaesthetics, and concerning processing of art, which suggest that perception may involve a natural sequence from first processing for hedonic quality (i.e., liking) followed by processing for understanding. Thus, due to the initial liking assessment's capacity to prime deepened cognitive involvement, a Liking Understanding order may show key differences in final assessments or brain activation when compared to an Understanding-Liking sequence. Thirty-two participants evaluated a range of paintings, balanced for visual appeal and understandability, in a two-part task in which half evaluated for understanding followed by liking and the other half had question order reversed. Brain activity was recorded via functional Near Infrared Spectroscopy (fNIRS). Results showed no assessment interrelation or order effect in artwork evaluations. However, participants who began with evaluation for liking, and who came to incongruent combinations (i.e., "I like, but I don't understand" or "I don't like, but I understand"), showed significantly higher activation in left medial prefrontal cortex. This area is functionally associated with attention and integration of hedonic/informational elements. Findings provide tentative support for a liking driven order-effect, as well as for physiological connection between appraisals, which may not appear in behavioral evidence, and suggest need for further consideration of this topic in appraisal research. PMID- 27393914 TI - Cognitive functioning in children from Nigeria with sickle cell anemia. AB - BACKGROUND: Cognitive impairment is a major neurological complication of sickle cell anemia (SCA) in the United States, but there are limited studies of cognitive impairment in Nigeria, the country with the highest SCA burden. We hypothesized that children from Nigeria with SCA have worse cognitive functioning than comparison children and explored the association between lower cognitive functioning and key laboratory demographic and socioeconomic variables among children with SCA. PROCEDURE: We conducted a cross-sectional survey, supplemented by anthropomorphic and laboratory data, among a convenience sample of children from Nigeria with and without SCA. We administered the Wechsler Intelligence Scale for Children, Version IV. Our primary outcome measures included (1) estimated IQ (Est. IQ), (2) working memory (WM), and (3) processing speed (PS). RESULTS: The sample included 56 children with SCA (mean age 9.20 [SD 2.75], 46.43% girls) and 44 comparison children (mean age 9.41 [SD 2.49], 40.91% girls). Children with SCA performed worse on Est. IQ (84.58 vs. 96.10, P = 0.006) and PS (86.69 vs 96.91, P = 0.009) than comparison children. There was no significant difference in WM between both groups. Factors associated with lower Est. IQ and PS among children with SCA included age, maternal education, weight-for-age Z scores, and height-for age Z scores. CONCLUSION: In this small sample of children from Nigeria, we found worse cognitive functioning in children with SCA than in comparison children, and that sociodemographic and anthropomorphic factors were correlated with cognitive functioning. PMID- 27393915 TI - PM2.5 collected in China causes inflammatory and oxidative stress responses in macrophages through the multiple pathways. AB - Air pollution continues to increase in East Asia, particularly in China, and is considered to cause serious health problems. In this study, we investigated the toxicological properties of particulate matter <=2.5mm (PM2.5) collected in an urban area in China (Shenyang), focusing on inflammation and oxidative stress tightly linked to respiratory diseases. Exposure to PM2.5 significantly increased the expression levels of inflammatory (interleukin-1beta and cyclooxygenase-2) and oxidative stress (heme oxygenase1) genes in the mouse macrophages. PM2.5 caused inflammatory response was strongly suppressed by endotoxin neutralizer (polymyxin B) and knock-out of toll-like receptor 4, while oxidative stress was not. On the other hand, an antioxidant (N-acetylcystein) suppressed oxidative stress, but not inflammatory response. These results suggest that PM2.5 in the atmospheric environment of China causes inflammation and oxidative stress in macrophages via separate pathways. PMID- 27393916 TI - Cognitive-behavioral therapy for body dysmorphic disorder: A systematic review and meta-analysis of randomized controlled trials. AB - Body dysmorphic disorder (BDD) is a chronic and disabling psychiatric disorder unlikely to remit without treatment. A systematic review and meta-analysis of randomized controlled trials (RCTs) of cognitive-behavioral therapy (CBT) for BDD was conducted, including published and unpublished trials to 26th November 2015. Primary outcomes were validated BDD measures; secondary outcomes included depression and insight. Meta-regressions were conducted to examine potential effects of variables on the primary outcome, including socio-demographic variables, comorbidity, symptom severity/duration, concomitant medication, treatment duration, and methodological quality of the RCTs. Seven RCTs (N=299) met inclusion criteria. CBT was superior to waitlist or credible psychological placebo in reducing BDD (7 studies; delta=-1.22, 95% CI=-1.66 to -0.79) and depression symptoms (5 studies; delta=-0.49, 95% CI=-0.76 to -0.22). CBT was associated with improvements in insight/delusionality (4 studies; delta=-0.56, 95% CI=-0.93 to -0.19). Improvement in BDD was maintained after 2-4months follow up (3 studies; delta=-0.89, 95% CI=-1.24 to -0.54). Meta-regression analyses did not reveal any significant predictors of outcome. CBT is an efficacious treatment for BDD but there is substantial room for improvement. The specificity and long term effects of CBT for BDD require further evaluation using credible control conditions. Additional trials comparing CBT with pharmacological therapies, as well as their combination, are warranted. Tele-care options, such as Internet based CBT, hold great promise to increase access to evidence-based treatment for a majority of patients who need it and should be evaluated further. PMID- 27393917 TI - Hippocampal YKL-40 expression in rats after status epilepticus. AB - OBJECTIVE: This study aims to investigate rat hippocampal cartilage glycoprotein 39 (YKL-40) expression levels following status epilepticus (SE), and the potential mechanism of YKL-40 in SE-induced neuronal injury. METHODS: Seventy-two healthy adult male Sprague-Dawley rats were randomly assigned into two groups: control and SE groups. A lithium chloride-pilocarpine SE model was established, and the control group was injected with sodium chloride. The hippocampus was assessed at three, six, 12, 24 and 72h after SE. YKL-40 protein was detected via immunohistochemistry (n=6). Cellular YKL-40/neuronal nuclei antigen (NeuN) expression levels were determined with double immunofluorescence. YKL-40 mRNA was detected via quantitative real-time polymerase chain reaction (qRT-PCR, n=6). RESULTS: YKL-40 immunoreactivity was poor and was mainly localized to the cytoplasm within hippocampal CA3/CA4 neurons with limited immunoreactivity in the nucleus in the control group. Following SE, YKL-40 immunoreactivity exhibited a diffused distribution throughout the cytoplasm in neurons and increased distribution in the nucleus. CA3 and CA4 YKL-40 protein expression significantly increased at six hours post-SE (P<0.05), peaked at 12h (P<0.01), and decreased at 24h (P<0.05) and 72h (P<0.05) in the SE group, compared with the control group. Double-label immunofluorescence of YKL-40/NeuN exhibited a hippocampal CA3/CA4 neuron location. Furthermore, SE induced a significant increase inYKL-40 mRNA at six, 24, or 72h (P<0.05); which peaked at 12h (P<0.01). CONCLUSIONS: YKL-40 was expressed in neurons, and elevated rat hippocampal YKL-40 expression levels may be involved in the pathogenesis of injury following SE. PMID- 27393918 TI - Impact of microbial inoculation on biomass accumulation by Sulla carnosa provenances, and in regulating nutrition, physiological and antioxidant activities of this species under non-saline and saline conditions. AB - Bacteria (Pseudomonas sp. and Bacillus sp.) and/or the arbuscular mycorrhizal (AM) fungus Rhizophagus intraradices were able to improve growth, physiological and biochemical characteristics of four Sulla carnosa Desf. provenances (Sidi khlif, Thelja, Kalbia and Kerker) from Tunisia under both saline and non-saline conditions. S. carnosa is a salt-tolerant legume plant, native from North Africa. The intrinsic bacterial characteristics evidenced the fitness of these bacteria to support salt stress and to stimulate plant growth. Bacillus sp. produced more indol acetic acid (IAA) than Pseudomonas sp. and showed a great surviving capacity under salt conditions supporting its capacity to improve plant growth under stress conditions. The microorganisms applied also have a different potential to increase the nutritional and related plant growth parameters. It is noticeable that some provenances reached the highest level of growth when inoculated with Bacillus sp. in Sidi khlif or by Bacillus plus AMF in Kalbia, which increased shoot by 318% and root by 774%. In contrast, in Thelja and Kerker the impact of the test microorganisms was mainly evidenced at increasing nutritional and physiological functions. Salinity reduced some growth and physiological variables as stomatal conductance, photosynthetic pigments and photosynthetic efficiency and increased electrolyte leakage. However, the microbial inoculants compensated these detrimental effects in a degree depending on the S. carnosa provenance. These microorganisms also orchestrate antioxidant activities involved in adaptative responses in S. carnosa provenances. The intrinsic ability of inoculants allow us to select the provenance/microorganism combination which maximizes S. carnosa growth, nutrition and physiological/biochemical responses under salt and non-salt conditions. The results obtained support that the target microbial inocula are beneficial for the ecological stability if this Mediterranean legume. PMID- 27393919 TI - Effects of potato spindle tuber viroid infection on tomato metabolic profile. AB - Viroids are the smallest plant pathogens consisting of a single stranded circular RNA molecule with a strong secondary structure, lacking a coat protein or any other proteins. The mechanism of viroid pathogenicity has remained unclear. Recent advances in instrumentation and data mining have made it possible to study the effects of various stresses on primary and secondary metabolisms. Here, we have utilized metabolic profiling approach to show how PSTVd infection alters tomato metabolic profile and the related pathways. Three terminal leaflets of third true leaf of 20-day-old tolerant tomato cultivar 'Moneymaker' were mechanically inoculated by PSTVd intermediate variant cDNAs and samples were taken from eighth leaf, 19days post-inoculation. Metabolites were extracted and analyzed by gas chromatography/mass spectrometry (GC/MS) and subjected to statistical data analysis. Affected pathways were identified by Pathway Tools program and were compared with microarray data previously reported. The study showed that 79 metabolites changed significantly and 23 pathways were identified in relation to these metabolites. Fourteen of these pathways were similar to those reported in other works. The altered pathways in PSTVd infected tomato leaves included, eight cutin and wax biosynthesis, seven pathways that produce defense related compounds, two energy generator pathways, three hormone biosynthesis pathways, two signal transduction pathways, and one nucleotide biosynthesis pathway. Our data on up/down-regulation of pathways supported the data produced on their corresponding gene(s) up/down-regulation. PMID- 27393920 TI - Effects of salinity on leaf breakdown: Dryland salinity versus salinity from a coalmine. AB - Salinization of freshwater ecosystems as a result of human activities represents a global threat for ecosystems' integrity. Whether different sources of salinity with their differing ionic compositions lead to variable effects in ecosystem functioning is unknown. Therefore, the present study assessed the impact of dryland- (50MUS/cm to 11,000MUS/cm) and coalmine-induced (100MUS/cm to 2400MUS/cm) salinization on the leaf litter breakdown, with focus on microorganisms as main decomposer, in two catchments in New South Wales, Australia. The breakdown of Eucalyptus camaldulensis leaves decreased with increasing salinity by up to a factor of three. Coalmine salinity, which is characterised by a higher share of bicarbonates, had a slightly but consistently higher breakdown rate at a given salinity relative to dryland salinity, which is characterised by ionic proportions similar to sea water. Complementary laboratory experiments supported the stimulatory impact of sodium bicarbonates on leaf breakdown when compared to sodium chloride or artificial sea salt. Furthermore, microbial inoculum from a high salinity site (11,000MUS/cm) yielded lower leaf breakdown at lower salinity relative to inoculum from a low salinity site (50MUS/cm). Conversely, inoculum from the high salinity site was less sensitive towards increasing salinity levels relative to inoculum from the low salinity site. The effects of the different inoculum were the same regardless of salt source (sodium bicarbonate, sodium chloride and artificial sea salt). Finally, the microorganism-mediated leaf litter breakdown was most efficient at intermediate salinity levels (~500MUS/cm). The present study thus points to severe implications of increasing salinity intensities on the ecosystem function of leaf litter breakdown, while the underlying processes need further scrutiny. PMID- 27393921 TI - Appearance comparisons styles and eating disordered symptoms in women. AB - The purpose of this study was to examine the relationship between styles of upward and downward appearance comparisons and eating disordered symptoms in women. Data on upward and downward appearance comparisons, body dissatisfaction, drive for thinness, dietary restraint, and negative body talk were collected from 321 female college students. Results indicated that upward appearance comparisons were linked to higher levels of drive for thinness, body dissatisfaction, dietary restraint, and negative body talk, whereas downward appearance comparisons were linked to higher levels of drive for thinness and dietary restraint, but showed no relationship to body dissatisfaction and negative body talk. There was an interaction effect between upward and downward comparisons and body image variables. Taken together, this study suggests that downward appearance comparison does not buffer the negative effects of upward appearance comparison, and in some cases can increase negative body image outcomes. PMID- 27393922 TI - Parenting very preterm infants and stress in Neonatal Intensive Care Units. AB - BACKGROUND: Assessing parental stress during infants' hospitalization in Neonatal Intensive Care Units (NICU) is essential to identify parents at risk for immediate and extended physical and emotional burden. AIMS: To identify sources of stress in mothers and fathers of very preterm infants hospitalized in NICU, and their association with sociodemographic, obstetric and infants' characteristics. STUDY DESIGN: Observational and cross-sectional study conducted between July 2013 and June 2014. SUBJECTS: Parents of very preterm infants hospitalized in all level III NICU in the Northern Health Region of Portugal were consecutively and systematically invited to participate in this study, being included 120 mothers and 91 fathers (participation rate: 96.8%). OUTCOME MEASURES: The Portuguese version of the Parental Stressor Scale: Neonatal Intensive Care Unit was used. RESULTS: The overall experience of hospitalization was classified as more stressful than the median for the subscales. "Change in parental role" was classified as the most stressful subscale by mothers (Median (P25-P75): 4.1(3.2-4.7)) and fathers (Median (P25-P75): 3.2(2.4-4.0)). Mothers scored significantly higher in all subscales. For mothers, multiple pregnancy was associated with lower levels of stress regarding "change in parental role" (beta= 0.597; 95% CI=-1.020 to -0.174) and "overall stress" (beta=-0.603; 95% CI=-1.052 to -0.153). Being >=30years old was found to be a significant predictor for decreased fathers' stress. CONCLUSIONS: This study raises awareness for the need to develop sensitive instruments that take notice of gender, social support and family-centered care. The implementation of interventions focused on reducing parental stress is crucial to diminish disparities in family health. PMID- 27393923 TI - Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool. AB - OBJECTIVE: Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. METHODS: We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. RESULT: Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. CONCLUSION: The diagnostic properties of the items and their correlations with post thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool. PMID- 27393924 TI - Relationship between metabolites of arachidonic acid and prognosis in patients with acute coronary syndrome. AB - OBJECTIVE: To investigate the correlation of arachidonic acid (ARA) metabolites and prognosis in ACS patients. METHODS AND RESULTS: This is a mono-center retrospective nested case-control study. We followed up 470 ACS patients, of whom 39 patients had MACE in a mean follow up time of 1037days (identified as MACE group). Another 39 clinically matched patients without MACE were selected from the 470 ACS patients (Non-MACE group). Thirty-nine subjects without Coronary Heart Disease were enrolled as Control group. Metabolites of ARA were determined by LC-MS/MS. We found that plasma levels of LTB4, 8-HETE, 11-HETE, 12-HETE, and 15-HETE were significantly increased in MACE and Non-MACE groups, 5-HETE and 9 HETE were significantly increased in MACE group comparing with Control group (P<0.05). Importantly, plasma level of 19-HETE in MACE group was significantly lower than Non-MACE and Control groups. 19-HETE significantly correlated with the prognosis of ACS after adjustment for clinical characteristics (HR=0.103, 95% C.I.: 0.014-0.766). The AUC for ROC curve of 19-HETE in predicting MACE was 0.637 (P<0.05). Survival analysis showed that ACS patients with 19-HETE levels higher than 0.13ng/ml tend to have better prognosis than those lower than 0.13ng/ml (P<0.05). GRACE score and serum Fib levels were also significantly correlated with MACE. 20-HETE level was found significantly higher in STEMI group comparing with NSTE-ACS group (P<0.05). CONCLUSION: Plasma arachidonic acid metabolites may act as prognostic markers for ACS patients. PMID- 27393925 TI - The effectiveness of antioxidant therapy in aspirin resistance, diabetes population for prevention of thrombosis. AB - Thrombosis as the main complication of coronary heart disease (CHD) represents the primary cause of morbidity and mortality in patients with diabetes mellitus (DM). In the course of diabetes mellitus some coagulation abnormalities occur, that may result in a thrombogenic propensity. Aspirin (ASA) as a platelet inhibiting agent through inactivation of Cyclooxygenase-1 (COX-1) is mostly used for the prevention and treatment of atherothrombotic disorders. ASA inhibits the COX-1 enzyme and therefore blocks platelet thromboxane A2 (TXA2) synthesis. However, some of the serious vascular events in high-risk vascular patients are attributable to a failure of ASA to suppress platelet aggregation. The consumption of antioxidant or antioxidant rich foods such as vitamin C, E, and polyphenols might impart anti-thrombotic and cardiovascular protective effects via their inhibition of platelet hyper-activation or aggregation similar to the action of aspirin. This review will discuss the risk of thrombosis in diabetes, what aspirin resistance means, and the effectiveness of antioxidant therapy in the prevention and possible treatment of atherothrombotic disorders. PMID- 27393926 TI - Sex differences regarding the amelioration of wrinkles due to skin dryness by the administration of tranexamic acid. AB - Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) exerts an amelioration effect on wrinkle formation due to skin dryness. We examined the sex differences in this effect. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to male and female Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In the treated female mice, the amelioration effect on the wrinkle score, deterioration of transepidermal water loss (TEWL), capacitance, and decrease in the expression of collagen type I was stronger than in the male treated mice. Furthermore, the level of beta-endorphin in the plasma and the expression of beta-endorphin, MU opioid receptor, and macrophages in the dorsal skin increased after the administration of tranexamic acid, and this increase was higher in female mice than in males. In addition, the macrophage production was increased by the administration of tranexamic acid in the ovary but did not change after administration in the testes. A histological examination revealed that these macrophages produce the beta-endorphin, clarifying the source of the elevated levels. The amelioration effect in the female treated mice was decreased by the administration of clophosome (a macrophage inhibitor) to a degree that did not markedly differ from the effect observed in the male treated mice. These results suggest that the amelioration effect on wrinkles is stronger in female NOA mice than in males and that beta-endorphin produced by macrophages plays an important role in this sex difference. PMID- 27393927 TI - Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-kappaB related signaling. AB - In many liver disorders, oxidative stress-related inflammation and apoptosis are important pathogenic components, finally resulting in acute liver failure. Erythropoietin and its analogues are well known to influence the interaction between apoptosis and inflammation in brain and kidney. The study is to clarify the effect of curcumin, a natural plant phenolic food additive, on lipopolysaccharides (LPS)-induced acute liver injury of mice with endotoxemia and associated molecular mechanism from inflammation, apoptosis and oxidative stress levels. And curcumin, lowered serum cytokines, including Interleukin 1beta (IL 1beta), Interleukin 6 (IL-6) and tumor necrosis factor (TNF-alpha), and improved liver apoptosis through suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibiting Cyclic AMP-responsive element binding protein (CREB)/Caspase expression, and decreased oxidative stress associated protein expression, mainly involving 2E1 isoform of cytochrome P450/nuclear factor E2-related factor 2/reactive oxygen species (CYP2E/Nrf2/ROS) signaling pathway, as well as liver nitric oxide (NO) production in LPS-induced mice. Moreover, curcumin regulated serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), accelerated liver antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-px) levels, and inhibited activation of the mitogen-activated protein kinases/c-Jun NH2-terminal kinase (P38/JNK) cascade in the livers of LPS-induced rats. Thus, curcumin treatment attenuates LPS-induced PI3K/AKT and CYP2E/Nrf2/ROS signaling and liver injury. Strategies to inhibit inflammation and apoptosis signaling may provide alternatives to the current clinical approaches to improve oxidative responses of endotoxemia. PMID- 27393928 TI - Is furcation involvement affected by adjunctive systemic amoxicillin plus metronidazole? A clinical trials exploratory subanalysis. AB - OBJECTIVES: Evaluation of the clinical effect of systemic amoxicillin and metronidazole adjunctively to mechanical debridement at furcation sites. MATERIAL AND METHODS: This is an exploratory per-protocol collective subanalysis from a prospective, randomized, double-blind, multi-centre trial (ClinicalTrials.gov NCT00707369) on the effect of adjunctive systemic amoxicillin 500 mg plus metronidazole 400 mg (3*/day, 7 days) use on furcation involvement in moderate to severe periodontitis. Outcome was the change in frequency of classes of furcation involvement after 27.5 months. Therapy comprised mechanical debridement in conjunction with antibiotic or placebo administration, and maintenance therapy at three months intervals. RESULTS: Three hundred and forty-five patients (175 placebo, 170 antibiotics) with 6576 furcation sites (class 0 2956; class I 2370; class II 886; class III 364) were examined (3472 placebo, 3104 antibiotics). Pocket reduction/attachment gain at the furcation sites was noticeably better after antibiotics (1.2/0.6 mm) than after placebo (0.7/0.2 mm) 27.5 months after therapy. However, most furcation degrees were unchanged (placebo 61.5%/antibiotics 62.2%), more sites improved than deteriorated (20.3%/18.2%, 22.1%/15.7% respectively) and no differences in the change of furcation degrees between treatments could be detected. CONCLUSION: Compared to placebo, prescription of adjunctive systemic antibiotics failed to show clinically relevant benefit with regard to furcation class involvement. PMID- 27393929 TI - Tracking the time course of lexical access in orthographic production: An event related potential study of word frequency effects in written picture naming. AB - Previous studies of spoken picture naming using event-related potentials (ERPs) have shown that speakers initiate lexical access within 200ms after stimulus onset. In the present study, we investigated the time course of lexical access in written, rather than spoken, word production. Chinese participants wrote target object names which varied in word frequency, and written naming times and ERPs were measured. Writing latencies exhibited a classical frequency effect (faster responses for high- than for low-frequency names). More importantly, ERP results revealed that electrophysiological activity elicited by high- and low frequency target names started to diverge as early as 168ms post picture onset. We conclude that lexical access during written word production is initiated within 200ms after picture onset. This estimate is compatible with previous studies on spoken production which likewise showed a rapid onset of lexical access (i.e., within 200ms after stimuli onset). We suggest that written and spoken word production share the lexicalization stage. PMID- 27393930 TI - Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center in Tours. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of PER as add-on treatment in patients with severe refractory epilepsy with a particular focus on patients with learning disability and/or psychiatric comorbidity. METHOD: We pooled retrospective data from adult patients with refractory epilepsy prescribed perampanel from a tertiary center in France between 1st May 2014 and 3rd June 2015. Data collection was done on February 2016. RESULTS: One hundred and one patients were included (mean age: 41.2years, 37.6% with learning disability and 49.5% with psychiatric comorbidity). Mean retention was 8.1months (range: 14days to 17months). On final evaluation, a >50% reduction in seizure frequency was reached in 41.6% of patients, and 7 patients (6.9%) became seizure-free. Sixty-three patients (62.4%) experienced adverse effects. The most common adverse effects were irritability, asthenia, aggression, and sedation. Efficacy, retention of treatment, and safety were equally similar in patients with learning disability or psychiatric comorbidity as for those without. The only significant difference was in percentage of seizure-free patients: 11.1% in the group without learning disability compared with 0% in the group with (p=0.043). CONCLUSION: Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in more than one-third of patients suffering from severe refractory epilepsies. It seems similarly safe and effective in the subgroup of these patients with learning disability or with psychiatric comorbidity. However, the rate of psychiatric side effects is high,; of note, we asked both patient and caregivers at each visit especially focusing on psychiatric side effects. Patients, caregivers, and families should be informed of potential psychiatric/behavioral risks associated with taking perampanel especially during the initial titration period. PMID- 27393931 TI - Intramolecular diffusion controls aggregation of the PAPf39 peptide. AB - The 39-residue fragment of human prostatic acidic phosphatase (PAP) is found in high concentrations in semen and easily form fibrils. Previous work has shown that fibrillization is accelerated with a deletion of the first 8, mostly charged residues and it was hypothesized that fibrillization depended on the dynamics of these peptides. To test this hypothesis we have measured the intramolecular diffusion of the full length and 8-residue deletion peptides at two different pHs and found a correlation with fibrillization lag time. These results can be explained by a simple kinetic model of the early stages of aggregation in which oligomerization is controlled by the rate of peptide reconfiguration. PMID- 27393932 TI - Compounding risk: An examination of associations between spirituality/religiosity, drinking motives, and alcohol-related ambivalence among heavy drinking young adults. AB - OBJECTIVES: The present study assessed combinations of spirituality/religiosity (S/R), a known protective factor against heavy drinking, with drinking motives, and alcohol-related ambivalence to better understand how these factors interrelate and are associated with drinking and alcohol-related problems. METHODS: Participants were 241 heavy drinking undergraduate students (81.74% female; Mage=23.48years; SD=5.50) who completed study questionnaires online. RESULTS: Coping, enhancement, and conformity drinking motives were associated with greater alcohol use and problems, however there were no main effects of either ambivalence or S/R on alcohol outcomes. S/R interacted with ambivalence with respect to drinking and problems. S/R also interacted with conformity drinking motives with respect to drinking and problems. Further, ambivalence interacted with conformity drinking motives regarding problems. Three-way interactions emerged between ambivalence, S/R, and drinking motives (social, coping, and enhancement motives) regarding drinking and problems. Results show that individuals at highest risk for problematic drinking are those who more strongly endorse drinking motives, are low in S/R, and high in ambivalence. CONCLUSIONS: Findings supported hypotheses and provide support for clusters of individual difference factors that put heavy drinking college students at higher risk for problematic drinking. These examinations have practical utility and may inform development and implementation of interventions and programs targeting alcohol misuse among heavy drinking undergraduate students. PMID- 27393933 TI - Psychographic characteristics, tobacco, and alcohol use in a sample of young adults on the U.S./Mexico border. AB - Few studies using psychographic segmentation have been conducted; even fewer in minority samples. Study aims were to identify psychographic clusters and their relation to tobacco and alcohol use within a predominantly Hispanic (87%) young adult (ages 18-25) sample. Participants (N=754; 72.5% female; Mage=20.7 [2.2]) completed the following measures online: sociodemographics, tobacco use history, the Daily Drinking Questionnaire (Collins, Parks, & Marlatt, 1985), a social activities scale, a psychographic survey, a music preference item, the Brief Sensation Seeking Scale (Hoyle, Stephenson, Palmgreen, Lorch, & Donohew, 2002), and the Mini-International Personality Item Pool (Donnellan, Oswald, Baird, & Lucas, 2006). Two step cluster analysis identified two groups. 'Popular Extroverts' (49.3% of sample) reported higher: extroversion scores F(1, 652)=40.03, sensation seeking scores F(1, 652)=20.38, alcohol use (greater number of drinks per week [F(1, 652)=9.69]; and past month binge drinking [chi2 (1)=12.80]), and lifetime tobacco use (chi2 [1]=10.61) (all ps<=0.002). 'Mainstream/Conventionals' (50.7% of sample) reported greater intentions to smoke in the next month F(1, 284)=11.81, p=0.001. 'Popular Extroverts' may benefit from prevention/cessation messaging promoting peer support and intensity-oriented activities. For 'Mainstream/Conventionals,' messaging communicating negative attitudes toward smoking and the tobacco industry may be effective. Future directions include testing targeted messages which may be incorporated into mass media tobacco and alcohol interventions for young adults on the U.S./Mexico border. PMID- 27393934 TI - Associations between tobacco and nicotine product use and depressive symptoms among college students in Texas. AB - BACKGROUND: There is a well-established link between cigarette smoking and depression; less is known about the potential association between alternative tobacco products, such as hookah, cigars, smokeless tobacco, and electronic cigarette (e-cigarette use) with depression. The Food and Drug Administration (FDA) is now regulating tobacco products and is interested in tobacco product use among those with mental health problems and other special populations such as college students. METHODS: Cross-sectional statewide convenience sample study of 5438 college students in 24 colleges and universities in Texas. Past 30-day use of hookah, cigar, smokeless tobacco, cigarette, and e-cigarette use were measured by self-report. Depressive symptoms were measured by the 10-item short form of the Center for Epidemiologic Studies scale. RESULTS: Only e-cigarette use was positively associated with depressive symptoms, even after accounting for all other tobacco products and socio-demographics. There were no significant interactions between race/ethnicity or gender with each of the tobacco products on depressive symptoms. CONCLUSIONS: E-cigarette use was positively associated with depressive symptoms among college students in Texas. Further research is needed to determine causality, which may inform FDA regulatory planning. PMID- 27393935 TI - Chemo-mechanical modification of cottonwood for Pb(2+) removal from aqueous solutions: Sorption mechanisms and potential application as biofilter in drip irrigation. AB - Using biomass (e.g. crop residues) and its derivatives as biosorbents have been recognized as an eco-friendly technique for wastewater decontamination. In this study, mechanically modified cottonwood was further activated with KOH to improve its sorption of Pb(2+). In addition, its potential as a biofilter to safeguard radish (Raphanus sativus, L.) against Pb-stress was evaluated in a gravity-fed drip irrigation system. Physiochemical properties of the chemo-mechanically activated cottonwood (CMACW) and the mechanically activated cottonwood (MACW) before and after sorption process were characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), digital selected-area electron diffraction (SAED) and Fourier transform infrared spectroscopy (FTIR). After activation, several sorption mechanisms (i.e. precipitation, electrostatic outer- and inner-sphere complexation) were responsible for the higher sorption capacity of CMACW as compared with MACW (8.55 vs. 7.28 mg g(-1)). Sorption kinetics and isotherms fitted better with the pseudo-second-order and Langmuir models as compared with the pseudo-first-order and Freundlich models, respectively. In the gravity-fed drip irrigation system, the CMACW biofilter reduced the accumulation of Pb in radish roots and shoots and avoided reaching the toxic limits in some cases. Soil types had a significant effect on Pb(2+) bioavailability because of the difference in sorption ability. Findings from this study showed that CMACW biofilter can be used as a safeguard for wastewater irrigation. PMID- 27393937 TI - Root signals that mediate mutualistic interactions in the rhizosphere. AB - A recent boom in research on belowground ecology is rapidly revealing a multitude of fascinating interactions, in particular in the rhizosphere. Many of these interactions are mediated by photo-assimilates that are excreted by plant roots. Root exudates are not mere waste products, but serve numerous functions to control abiotic and biotic processes. These functions range from changing the chemical and physical properties of the soil, inhibiting the growth of competing plants, combatting herbivores, and regulating the microbial community. Particularly intriguing are root-released compounds that have evolved to serve mutualistic interactions with soil-dwelling organisms. These mutually beneficial plant-mediated signals are not only of fundamental ecological interest, but also exceedingly important from an agronomical perspective. Here, we attempt to provide an overview of the plant-produced compounds that have so far been implicated in mutualistic interactions. We propose that these mutualistic signals may have evolved from chemical defenses and we point out that they can be (mis)used by specialized pathogens and herbivores. We speculate that many more signals and interactions remain to be uncovered and that a good understanding of the mechanisms and ecological implications can be the basis for exploitation and manipulation of the signals for crop improvement and protection. PMID- 27393939 TI - Prevalence of hepatitis B virus in the Kurram Agency, Pakistan: A 5-year observational study in a war-affected region. AB - BACKGROUND: Hepatitis B is an inflammatory liver illness caused by the hepatitis B virus. The exact magnitude and extent of the hepatitis B virus in Pakistan is still unknown, but at least 10 million people are estimated to be infected with chronic hepatitis B virus. OBJECTIVES: The objective of this study was to determine the seroprevalence of hepatitis B surface antigen (HBsAg) in the war affected area since 2009. STUDY DESIGN: Observational study. RESULTS: A total of 4922 healthy subjects were tested for the detection of HBsAg during 2009-2013, and 14.95% subjects were found to be reactive for HBsAg. The highest seroprevalence (26.0%) of HBsAg was found in those individuals who were less than 35 years of age. Male subjects were more affected (16.6%) than females. The seroprevalence of HBsAg was significantly associated with <35 years of age and male gender (P<0.005 for both). Moreover, an increasing trend over 5 years was observed, as 8.6% subjects were positive for HBsAg in 2009 and subsequently 10.4% in 2010, 14.6% in 2011, 18.9% in 2012, and 21.7% were reactive for HBsAg in 2013. CONCLUSION: This study concluded that HBsAg was more prevalent in the war affected region. The prevalence rate was increasing with time as the highest rate was found in 2013. Present observations will help to provide the background for awareness and bring the increasing levels of hepatitis B to the attention of health professionals and government authorities in order to increase the capacity of the health systems in such troubled areas. PMID- 27393938 TI - Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15. AB - BACKGROUND: Hepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies. STUDY: Countries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases. RESULTS: Surveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs. CONCLUSION: Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the 'One Health' approach to better informing on human exposure to HEV. PMID- 27393940 TI - Role of plants in nitrogen and sulfur transformations in floating hydroponic root mats: A comparison of two helophytes. AB - Knowledge about the roles helophytes play in constructed wetlands (CWs) is limited, especially regarding their provision of organic rhizodeposits. Here, transformations of inorganic nitrogen and sulfur were monitored in a CW variety, floating hydroponic root mat (FHRM), treating synthetic wastewater containing low concentration of organic carbon. Two helophytes, Phragmites australis and Juncus effusus, were compared in duplicates. Striking differences were found between the FHRM of the two helophytes. Whereas ammonium was removed in all FHRMs to below detection level, total nitrogen of 1.15 +/- 0.4 g m(-2) d(-1) was removed completely only in P. australis systems. The mats with J. effusus displayed effective nitrification but incomplete denitrification as 77% of the removed ammonium-nitrogen accumulated as nitrate. Furthermore, the P. australis treatment units showed on average 3 times higher sulfate-S removal rates (1.1 +/- 0.45 g m( 2) d(-1)) than the systems planted with J. effusus (0.37 +/- 0.29 g m(-2) d(-1)). Since the influent organic carbon was below the stoichiometric requirement for the observed N and S transformation processes, helophytes' organic rhizodeposits apparently contributed to these transformations, while P. australis provided about 6 times higher bioavailable organic rhizodeposits than J. effusus. PMID- 27393941 TI - Modeling BOD and COD removal from Palm Oil Mill Secondary Effluent in floating wetland by Chrysopogon zizanioides (L.) using response surface methodology. AB - While the oil palm industry has been recognized for its contribution towards economic growth and rapid development, it has also contributed to environmental pollution due to the production of huge quantities of by-products from the oil extraction process. A phytoremediation technique (floating Vetiver system) was used to treat Palm Oil Mill Secondary Effluent (POMSE). A batch study using 40 L treatment tanks was carried out under different conditions and Response Surface Methodology (RSM) was applied to optimize the treatment process. A three factor central composite design (CCD) was used to predict the experimental variables (POMSE concentration, Vetiver plant density and time). An extraordinary decrease in organic matter as measured by BOD and COD (96% and 94% respectively) was recorded during the experimental duration of 4 weeks using a density of 30 Vetiver plants. The best and lowest final BOD of 2 mg/L was obtained when using 15 Vetiver plants after 13 days for low concentration POMSE (initial BOD = 50 mg/L). The next best result of BOD at 32 mg/L was obtained when using 30 Vetiver plants after 24 days for medium concentration POMSE (initial BOD = 175 mg/L). These results confirmed the validity of the model, and the experimental value was determined to be quite close to the predicted value, implying that the empirical model derived from RSM experimental design can be used to adequately describe the relationship between the independent variables and response. The study showed that the Vetiver system is an effective method of treating POMSE. PMID- 27393942 TI - Transport of hydraulic fracturing waste from Pennsylvania wells: A county-level analysis of road use and associated road repair costs. AB - Pennsylvania's rapid unconventional oil and gas (UOG) development-from a single well in 2004 to more than 6700 wells in 2013-has dramatically increased UOG waste transport by heavy trucks. This study quantified the amount of UOG waste and the distance it traveled between wells and disposal facilities on each type of road in each county between July 2010 and December 2013. In addition, the study estimated the associated financial costs to each county's road infrastructure over that period. We found that UOG wells produced a median wastewater volume of 1294 m(3) and a median of 89,267 kg of solid waste. The median number of waste transport truck trips per well was 122. UOG wells existed in 38 Pennsylvania counties, but we estimated trucks transporting well waste traveled through 132 counties, including counties in West Virginia, Ohio, and New York. Median travel distance varied by disposal type, from 106 km to centralized treatment facilities up to 237 km to injection wells. Local roads experienced the greatest amount of truck traffic and associated costs ($1.1-6.5 M) and interstates, the least ($0.3 1.6 M). Counties with oil and gas development experienced the most truck traffic and incurred the highest associated roadway costs. However, many counties outside the active development area also incurred roadway repair costs, highlighting the extension of UOG development's spatial footprint beyond the active development area. An online data visualization tool is available here: www.nicholasinstitute.duke.edu/transportation-of-hydraulic-fracturing-waste. PMID- 27393943 TI - Silvopastoral systems of the Chol Mayan ethnic group in southern Mexico: Strategies with a traditional basis. AB - Silvopastoral systems combine trees and/or shrubs with grazing cattle. In the municipality of Salto de Agua, Chiapas, Mexico, some indigenous communities have developed silvopastoral systems based on their traditional knowledge regarding use of local natural resources. Through analysis of classification based on the composition of tree vegetation, two groups of grazing units were identified in the study area. Different attributes of tree and herbaceous vegetation, as well as of agricultural management and production, were compared between the two groups. Results indicate that at least two strategies of silvopastoral management exist. The first - LTD - is characterized by an average density of 22 adult trees ha(-1) in grazing units with an average surface area of 22.4 ha. The second - HTD - has an average of 54.4 trees ha(-1) in grazing units with an average surface area of 12.2 ha. Average richness per grazing unit for the LTD strategy was 7.2 species, and for HTD strategy it was 12.7 species. Average basal area for LTD was 1.7 m2 ha(-1), and for HTD 3.8 m2 ha(-1). Finally, the average level of fixed carbon for LTD was 2.12 mg ha(-1), and for HTD 4.89 mg ha(-1). For all variables, there was a significant difference between the two strategies. In addition, both strategies differ in prairie management. In the HTD strategy, growers spare their preferred spontaneously growing tree species by clearing around them. Many of these species, particularly those harvested for timber, belong to the original vegetation. In these prairies, average coverage of native grasses (60.8 +/- 7.85) was significantly greater than in the LTD strategy (38.4 +/- 11.32), and neither fertilizers nor fire are used to maintain or improve the pastures; by contrast, in HTD prairies, introduced grasses, principally Cynodon plectostachyus, have a higher average coverage (43.4 +/- 13.75) than in the LTD prairies (17.08 +/- 9.02). Regardless of the differences in composition of tree and herbaceous vegetation, in both types of grazing units a similar animal load is maintained. Many attributes of these silvopastoral strategies - based on traditional technology of the Chol farmers of the Tulija River Valley - concord with sustainable agriculture and provide a wide variety of services to the farmer and the environment. Diffusion of this technology in areas similar to that of this region could have a positive impact on the economy of conventional cattle raisers while generating environmental services. PMID- 27393944 TI - Improving plant bioaccumulation science through consistent reporting of experimental data. AB - Experimental data and models for plant bioaccumulation of organic contaminants play a crucial role for assessing the potential human and ecological risks associated with chemical use. Plants are receptor organisms and direct or indirect vectors for chemical exposures to all other organisms. As new experimental data are generated they are used to improve our understanding of plant-chemical interactions that in turn allows for the development of better scientific knowledge and conceptual and predictive models. The interrelationship between experimental data and model development is an ongoing, never-ending process needed to advance our ability to provide reliable quality information that can be used in various contexts including regulatory risk assessment. However, relatively few standard experimental protocols for generating plant bioaccumulation data are currently available and because of inconsistent data collection and reporting requirements, the information generated is often less useful than it could be for direct applications in chemical assessments and for model development and refinement. We review existing testing guidelines, common data reporting practices, and provide recommendations for revising testing guidelines and reporting requirements to improve bioaccumulation knowledge and models. This analysis provides a list of experimental parameters that will help to develop high quality datasets and support modeling tools for assessing bioaccumulation of organic chemicals in plants and ultimately addressing uncertainty in ecological and human health risk assessments. PMID- 27393945 TI - Monopersulfate photocatalysis under 365 nm radiation. Direct oxidation and monopersulfate promoted photocatalysis of the herbicide tembotrione. AB - Oxone((r)) (potassium monopersulfate, MPS) has been used to oxidize the herbicide tembotrione in aqueous solution. Tembotrione elimination kinetics by MPS direct oxidation has been studied. The influence of the main operating variables affecting the process (MPS concentration, temperature and pH) has been evaluated. The process follows 2/3 and first orders in MPS and tembotrione concentrations, respectively. Optimal pH is located around circumneutral conditions. MPS decomposition in the presence of 365 nm UVA radiation and titanium dioxide has also been studied. A kinetic mechanism that simulates MPS decomposition has been proposed, showing the positive effect of titania load and MPS concentration. The system MPS/UVA/TiO2 significantly improves tembotrione and mineralization rate abatement if compared to runs conducted in the absence of MPS. Tembotrione total abatement was achieved in 20 min when 0.05 g L(-1) of titania and 10(-4) M of Oxone((r)) were used. TOC conversion was roughly 70% in 90 min under similar operating conditions. An experimental design (Plackett-Burman) has been considered to study the influence of the main variables affecting tembotrione photocatalytic oxidation promoted by MPS. PMID- 27393946 TI - Environmental impact from vermicomposting of organic waste in Kampala, Uganda. AB - Urban animal farming is becoming increasingly important in feeding the growing population of many sub-Saharan African cities. However, management of the animal manure generated is proving to be challenging due to space restrictions. Vermicomposting is one of the methods proposed to address this challenge. This study investigated the environmental performance of the vermicompost system by measuring the gaseous emissions generated from the system. In addition, the vermicompost system was compared with other manure management systems currently in use, using life cycle assessment (LCA) methodology. The emissions factors for the vermicompost system were found to be 10.8, 62.3 and 12.8 g/Megagram biowaste for methane, nitrous oxide and ammonia, respectively. LCA showed satisfactory performance of vermicomposting in terms of global warming and eutrophication potential, although if the vermicompost generated is dumped, this could lead to increased eutrophication. However, this is still much lower than the eutrophication caused by open dumping of untreated manure. PMID- 27393947 TI - Syntheses and photodynamic activity of some glucose-conjugated BODIPY dyes. AB - The syntheses of three water-soluble glucose-conjugated BODIPY dyes with different wavelength emissions and studies of their photodynamic therapeutic (PDT) action on human lung cancer A549 cell line are disclosed. Amongst the chosen compounds, the BODIPY dye 4 possessing a glycosylated styryl moiety at the C-3 position showed best PDT property against the A549 cell line. In particular, it induced reactive oxygen species-mediated caspase-8/caspase-3-dependent apoptosis as revealed from the increased sub G1 cell population and changes in cell morphology. These results along with its localization in the endoplasmic reticulum, as revealed by confocal microscopy suggested that mitochondria may not be directly involved in the photo-cytotoxicity of 4. Compound 4 did not induce any dark toxicity to the A549 cells, and was non-toxic to normal lung cells. PMID- 27393948 TI - Discovery of novel small molecule inhibitors of lysine methyltransferase G9a and their mechanism in leukemia cell lines. AB - Lysine methyltransferase G9a regulates the transcription of multiple genes by primarily catalyzing mono- and di-methylation of histone H3 lysine 9, as well as several non-histone lysine sites. An attractive therapeutic target in treating leukemia, knockout studies of G9a in mice have found dramatically slowed proliferation and self-renewal of acute myeloid leukemia (AML) cells due to the attenuation of HoxA9-dependent transcription. In this study, a series of compounds were identified as potential inhibitors through structure-based virtual screening. Among these compounds, a new G9a inhibitor, DCG066, was confirmed by in vitro biochemical, and cell based enzyme assays. DCG066 has a novel molecular scaffold unlike other G9a inhibitors presently available. Similar to G9a's histone substrate, DCG066 can bind directly to G9a and inhibit methyltransferase activity in vitro. In addition to suppressing G9a methyltransferase activity and reducing histone H3 methylation levels, DCG066 displays low cytotoxicity in leukemia cell lines with high levels of G9a expression, including K562. This work presents DCG066 as an inhibitor of G9a with a novel structure, providing both a lead in G9a inhibitor design and a means for probing the functionality of G9a. PMID- 27393949 TI - 2-Indolylmethylenebenzofuranones as first effective inhibitors of ABCC2. AB - ABC-transporters play a vital role in drugs bioavailability. They prevent intracellular accumulation of toxic compounds, rendering them a major defense mechanism against harmful substances. In this large family, ABCC2 is an apical efflux pump representing about 10% of all membrane proteins in liver and small intestine, and up to 25% in colon. In these tissues, ABCC2 plays a major role in the pharmacokinetics and pharmacodynamics of endo- and xenobiotics. To gain insight in the function of this crucial protein, we have investigated and developed the first effective inhibitors of this pump. Firstly, we set up a cellular flow cytometry assay for monitoring the drug efflux carried out by ABCC2, and used it for the screening of chemical libraries derived from several chemical classes. We found that 2-indolylmethylenebenzofuranone derivatives as promising candidates. Optimization of the hits provided new compounds that inhibit ABCC2 in the micromolar range, making them the first potent ABCC2 inhibitors reported so far. Such compounds would constitute valuable tools to further investigate the role of ABCC2 in the pharmacokinetics and pharmacodynamics of drugs. PMID- 27393950 TI - New imidazolidineiminothione derivatives: Synthesis, spectral characterization and evaluation of antitumor, antiviral, antibacterial and antifungal activities. AB - A series of new imidazolidineiminothione derivatives with various halogenated and alkylated aromatic substituents at N-(1) and at N-(3) was synthesized through the reaction of N-arylcyanothioformamides with arylisocyanate derivatives. Structure of imidazolidineiminothione derivatives were established based on spectroscopic IR, (1)H NMR, (13)C NMR, (1)H,(1)H-COSY, HSQC, (19)F NMR, MS and elemental analyses data. Evaluation of antitumor, antiviral, antibacterial and antifungal activities for the synthesized compounds were carried out to probe their activities. Most of the synthesized compounds displayed antitumor activity. The presence of 3,5-dichlorophenyl moiety at N-(1) and trichlorophenyl moiety on N (3) (2f) resulted the highest cytotoxic activity. The presence of 9H-fluorenyl moiety on N-(3) resulted in the lowest cytotoxic activity. The antiviral screening displayed that 2d and 2f were markedly active against one or two viral strains. Compound 2d (3,5-dichlorophenyl moiety at N-(1) and 4-chlorophenyl moiety on N-(3)) showed 100% antiviral effect toward HAV. Compound 2f showed 96.7% antiviral effect toward HSV1 and 80.3% antiviral effect toward HAV. The antimicrobial activity suggested that all of the imidazolidineiminothione derivatives possess significant antimicrobial activity against most of the test organisms. Some imidazolidineiminothione derivatives showed MIC values of antibacterial and antifungal activities ranged from 0.78 to 6.25 MUg/ml. PMID- 27393951 TI - Effects of vitrification protocol on the lactate dehydrogenase and total atpase activities of chinese mitten crab Eriocheir sinensis embryos. AB - BACKGROUND: Vitrification is the most promising option for the cryopreservation of fish embryos but requires high concentrations of potentially toxic cryoprotectants that can also cause cell injury, and affect cell division, enzymatic activities and cell metabolism. The effect of cryopreservation on the enzyme activity in crustacean embryos has not been reported. OBJECTIVES: The aim of this study was to investigate the effects of a vitrification protocol on the enzyme activity of different stages of Eriocheir sinensis embryos. The goal was to select an appropriate stage and vitrifying solution for the cryopreservation of embryos from this crustacean. MATERIALS AND METHODS: Embryos from E.sinensis at five development stages (cleavage, blastula, gastrula, eyed stage and heart beating stage) were submitted to six kinds of cryoprotectant incorporation protocol with a five stepwise method. Six vitrifying solutions were prepared by combining cryoprotectants PG, MeOH, Me(2)SO and DMF in different proportions (A: 20 % PG + 20 % DMF; B: 20 % MeOH+20 % DMF; C: 20 % PG+20 % MeOH; D:20 % PG+10 % MeOH+10 % DMF; E:20 % Me2SO+20 % PG;F:20 % Me(2)SO+20 % MeOH). After incubation in the six kinds of vitrification solutions, embryos were loaded into cryo-tubes and plunged into liquid nitrogen. The activities of two cytoplasmic enzymes, LDH and total ATPase were analyzed in control embryos, those subjected to the cryoprotectant solutions and in frozen/thawed embryos. RESULTS: The cryoprotectant incorporation protocol had important effects on the enzymatic activities, and different vitrifying solutions had distinct effects on the enzymatic activities. The early stage embryo was sensitive to the toxic effect of the cryoprotectants, with a significant drop in total ATPase in comparison with fresh, control embryos. Enzymatic activities dropped significantly after vitrification, indicating cell damage and loss of cytoplasmic enzymes. CONCLUSION: The composition of vitrifying solutions had different effects on the loss of the enzyme activity, and the later stage embryo was more resistant to the effect of vitrification. PMID- 27393952 TI - Vitrification-based cryopreservation of protocorm-like bodies of an endangered lady's slipper orchid: Paphiopedilum niveum (Rchb.f.) Stein. AB - BACKGROUND: Paphiopedilum niveum (Rchb.f.) Stein, an endangered lady's slipper orchid, is listed in CITES Appendix I and thus requires conserving. OBJECTIVE: The study aimed to cryopreserve protocorm-like bodies (PLBs) by a vitrification technique. MATERIALS AND METHODS: Four-month-old PLBs were precultured in modified Vacin and Went liquid medium with various sucrose concentrations for 24 h and 5 d with daily increasing sucrose concentrations followed by different exposure times to plant vitrification solution 2 (PVS2). RESULTS: Precultured PLBs in 0.75 M sucrose for 5 d with stepwise increase of sucrose and PVS2 for 90 min provided the highest viability after drying to low moisture content. The cryopreserved PLBs exhibited fewer dark stained nuclei and accumulated starch grains than those of the control. Cryopreserved PLBs had some shrunken epidermal cells, no change in ploidy level, a survival level of 22 % and the regenerated plantlets grew well. CONCLUSION: This study is the first report evaluating the success of cryopreserved PLBs of P. niveum via a vitrification protocol. PMID- 27393953 TI - Cryopreservation of in vitro shoot tips of strawberry by the vitrification method - establishment of a duplicate collection of Fragaria germplasm. AB - BACKGROUND: The National German Strawberry Genebank, which includes 183 cultivars and 270 accessions of wild Fragaria species, is maintained in a field collection of the Fruit Genebank at Dresden-Pillnitz. OBJECTIVE: A duplicate collection stored in liquid nitrogen would provide a higher level of security for these irreplaceable genetic resources. MATERIALS AND METHODS: Four distinct cryopreservation protocols were tested earlier and the best method, a PVS2 vitrification method with a 14-day alternating-temperature cold acclimation, was modified for further genotype screening. RESULTS: A comprehensive genotype spectrum was tested by screening 107 Fragaria *ananassa cultivars and 20 Fragaria wild species (51 accessions). The average recovery for the cultivars using the optimized medium was 89.55 % and for the wild species 85.50 %. CONCLUSION: These results indicate that the method could be used to establish a backup collection in liquid nitrogen. Meristem cultures will be established and the collection will be cryopreserved using this vitrification technique to provide cost effective long-term storage. PMID- 27393954 TI - Effect of cryoprotectant solution and of cooling rate on crystallization temperature in cryopreserved Hypericum perforatum cell suspension cultures. AB - BACKGROUND: The increasing demand for hypericins and hyperforins, the unique pharmaceuticals found in the Hypericum genus, requires the development of effective tools for long-term storage of cells and tissues with unique biochemical profiles. OBJECTIVE: To determine the temperature of crystallization (T(C)) and of ice formation of 14 cryoprotectant mixtures (CMs) for their use in cryoprotection of H. perforatum L. cell suspensions and to evaluate the impact of the lowest Tc on post-cryogenic recovery. MATERIALS AND METHODS: T(C) was determined by real-time microscopy of ice formation during slow cooling to -196 degrees C and heating to 20 degrees C. RESULTS: Exposure of cells to CMs CM2 (PVS3) containing sucrose and glycerol or CM12 and CM13 containing sucrose, glycerol, dimethylsulfoxide and ethylene glycol decreased T(C) below -60 degrees C, prevented intracellular crystallization and considerably reduced both the size of crystals and the rate of extracellular ice propagation. CONCLUSION: The selected CMs proved suitable for cryopreservation of H. perforatum cell suspensions with the maximum of 58 % post-thaw recovery. PMID- 27393955 TI - Positive effect of apoptotic inhibitor z-vad-fmk on vitrified-thawed porcine mii stage oocytes. AB - BACKGROUND: The developmental potential of vitrified porcine oocytes is very lower, and apoptosis is considered as one of the key factors involved. OBJECTIVE: To investigate the effects of apoptotic inhibitor Z-VAD-FMK addition into the incubation medium after warming on apoptosis and developmental ability of vitrified porcine MII-stage oocytes. MATERIALS AND METHODS: The activities of several caspases, mitochondrial membrane potential (DeltaPsim) and early apoptotic levels were measured. Parthenogenetic developmental ability and relative expression levels of apoptosis related genes were also detected. RESULTS: Caspase activity and early apoptotic level of the Z-VAD-FMK group were significantly lower than those of the group without Z-VAD-FMK addition, but were much higher than those of fresh group (P < 0.05). The DeltaPsim of Z-VAD-FMK group was 1.19, higher than the vitrified group (0.91) and lower than the fresh group (1.33). The cleavage rate and blastocyst rate after parthenogenetic activation in the Z-VAD-FMK group were much higher than those in the vitrified group, and much lower than those in the fresh group (P < 0.05). Vitrified porcine oocytes exhibited increased expression of pro-apoptotic genes (caspase 3, 8, 9, TNF-alpha) and decreased genes expression levels of anti-apoptotic genes (Bcl-2, CuZnSOD), and the Z-VAD-FMK addition in incubaiton medium significantly decreased the transcripts levels of caspase 3,8,9, Bax, TNF-alpha and increased Bcl-2 and CuZnSOD genes expression. CONCLUSION: The addition of apoptotic inhibitor Z-VAD FMK into the incubation medium after warming improved the in vitro developmental ability of vitrified porcine oocytes by increasing mitochondrial function, reducing apoptotic level and changing apoptosis-elated gene expression. PMID- 27393956 TI - Evolving trends in cryopreservation and parameters influencing semen extender preparation - a prospective review. AB - BACKGROUND: Cryopreservation is a technique by which, semen can be preserved to subzero temperature, usually at -196 degrees C. The freezing of semen desires vitrification mediators that diminish wreck to the cells (spermatozoan) during the freeze and thaw process. Using cryopreservation, the quality of the semen has been increased in the latest years, by which the achievement rate for the insemination techniques has increased in an agreed way. The area need to be focused is to enhance the quality of the semen extender preparation before cryopreservation. Many researchers are working in the area of cryopreservation of human semen with different semen extenders. Several parameters influence the properties of semen extender essential for better post thaw results. This review is mainly focused on a range of parameters which influence the best semen extender for cryopreservation that includes glycerol and its importance, buffer and novel usage of antimicrobial peptides as antimicrobial agents. PMID- 27393957 TI - Supercooling capacity and cryoprotectants of overwintering larvae from different populations of Holcocerus hippophaecolus. AB - BACKGROUND: Holcocerus hippophaecolus is the most serious pest occurred in seabuckthorn forest of three north areas. OBJECTIVE: The primary aims of the current study were to explore the physiological mechanisms and adaptability of H. hippophaecolus to low temperatures. MATERIALS AND METHODS: Assessing supercooling point, freezing point, and cryoprotectants of different larval instars from three different populations. RESULTS: Supercooling capacity of larvae from the 8-13 instar groups was relatively independent of temperature and other indicators such as latitude. Larvae from the 14-16 instar groups were sensitive to temperature and latitude, with generally lower limits and a wider range of SCPs than those of the other instar groups. CONCLUSION: For each population, the differences in the supercooling capacity of different instar stages for the identical period were not significant. The metabolism of fat and glycogen might not be the primary factors affecting the supercooling capacity. PMID- 27393958 TI - Effect of linker length and residues on the structure and stability of a fusion protein with malaria vaccine application. AB - BACKGROUND: Recombinant protein technology has revolutionized the world of biology and medicine. Following this progress, fusion protein technology, as a novel innovation, has opened new horizons for the development of proteins that do not naturally exist. Fusion proteins are generated via genetically fusing two or more genes coding for separate proteins, thus the product is a single protein having functional properties of both proteins. As an indispensable element in fusion protein construction, linkers are used to separate the functional domains in order to improve their expression, folding and stability. METHOD: We computationally fused an antigen and an adjuvant together using different linkers to obtain a two-domain fusion construct which can potentially act as an oral vaccine candidate against malaria. We then predicted the structures computationally to find out the probable folding of each domain in the designed construct. RESULTS: One of the fusion constructs was selected based on the highest value for C-score. Ramchandran Plot analysis represented that most residues were fallen in favorable regions. CONCLUSION: Our in silico analysis showed that (GGGGS)3 linker confers the best structure and stability for our target fusion protein. PMID- 27393959 TI - Differences in continuous spectra of fractionated electrograms in paroxysmal versus persistent atrial fibrillation. AB - INTRODUCTION: Quantitative measurements are helpful to discern fractionated electrograms in paroxysmal and persistent atrial fibrillation (AF), and may be useful to detect optimal ablation sites. However, electrical activation events can be transient, leading to erroneous estimates of electrogram properties. Measurement of continuous changes in electrogram frequency content may improve analysis. METHOD: Fractionated local electrograms from 10 paroxysmal and 10 persistent AF patients were acquired from outside the pulmonary vein ostia and left atrial free wall using the distal bipolar ablation catheter electrode, and analyzed over continuous 16 second intervals. A New Spectral Estimator (NSE) updated the frequency spectrum and spectral parameters once per millisecond. The tallest spectral peak (dominant frequency or DF) was determined. Statistical tests of variability were used to determine significant differences between paroxysmal and persistent AF. RESULTS: Changes in the value of the DF over 16 seconds were caused by transient drifts in the frequency of the dominant peak, or by changes in which peak had the highest amplitude. The continuous DF and the spectral profile parameters were more highly variable in paroxysmal as compared with persistent AF patients (p<0.001). There was found to be a gradient from high to low variability of DF in paroxysmal AF, from the left superior pulmonary vein antrum to the left atrial free wall. CONCLUSIONS: The results suggest that atrial electrical activation becomes more stable and focused at a narrow frequency range in persistent as compared to paroxysmal AF. The NSE implemented for continuous update of spectral parameters, enables a rapid characterization of fractionated electrograms with high time-frequency resolution and low computational cost. PMID- 27393960 TI - Differentiated thyroid cancer in patients >=75 years: Histopathological features and results of surgical treatment. AB - INTRODUCTION: The aim of this retrospective study was to investigate clinical and pathologic characteristics of differentiated thyroid cancer (DTC) in patients >=75 years and to analyze results of surgical treatment in this age group. METHODS: The clinical records of patients submitted to total thyroidectomy between 2009 and 2014 with histopathological diagnosis of DTC were analyzed. Patients were divided into 3 groups: patients <=64 years were included in group A, those between 65 and 74 in B and those >=75 years in C. RESULTS: Classic papillary thyroid cancer was more frequent in group A, whereas follicular variant of papillary carcinoma, tall cell and follicular carcinoma were more frequent in C. Multicentric and locally invasive tumors were more frequent in group C; younger patients (group A) showed higher incidence of node metastases (12.54% in group A, 6.33% in B and 7.89% in C). Postoperative stay was significantly longer in group C (3.13 +/- 1.28 days vs 2.55 +/- 1.27 vs 2.89 +/- 1.27; p < 0.001). Transient hypoparathyroidism was more frequent in groups A and B compared with C (29.26% vs 19.71% vs 18.42%; p 0.033) whereas transient recurrent laryngeal nerve palsy was more frequent in group C compared with A and B (2.63% vs 0.16% vs 2.11% p 0.009). CONCLUSIONS: In aging patients DTC show a worse prognosis compared with younger patients due to higher incidence of more aggressive histotypes but also to a significant diagnostic delay. Total thyroidectomy is safe when surgical operation is performed by skilled surgeons. Age alone does not exclude surgical option. PMID- 27393961 TI - Downregulated PIRH2 Can Decrease the Proliferation of Breast Cancer Cells. AB - BACKGROUND AND AIMS: We undertook this study to investigate the influence of PIRH2 (p53-induced RING-H2) protein on the proliferation and cell cycle of breast cancer cell lines. METHODS: PIRH2 expression was detected by Western blot analysis, immunohistochemistry (IHC) and Kaplan-Meier curve analysis. Cell proliferation was assessed by cell counting kit-8 (CCK-8). Cell cycle control was analyzed by flow cytometry. RESULTS: PIRH2 was up-regulated in breast cancer tissues and cell lines and up-regulated PIRH2 was highly associated with tumor size, grade, ER, and Ki-67. Moreover, Kaplan-Meier curve showed that up-regulated PIRH2 was related to the poor overall survival of patients with breast carcinoma. When the expression of PIRH2 was inhibited by siRNA transfection, cell proliferation was reduced. In addition, the number of G0/G1 phase cells was increased, but G2/M cells were not affected significantly. CONCLUSION: Decrease of PIRH2 expression in the breast cancer cell line MDA-MB-231 resulted in reduced tumor cell growth via the inhibition of cell proliferation and the interruption of cell cycle transition. PMID- 27393962 TI - Release and detection of nanosized copper from a commercial antifouling paint. AB - One major concern with the use of antifouling paints is the release of its biocides (mainly copper and zinc) into natural waters, where they may exhibit toxicity to non-target organisms. While many studies have quantified the release of biocides from antifouling paints, very little is known about the physicochemical state of released copper. For proper risk assessment of antifouling paints, characterization of copper released into water is necessary because the physicochemical state determines the metal's environmental fate and effects. In this study, we monitored release of different fractions of copper (dissolved, nano, and bulk) from a commercial copper-based antifouling paint. Release from painted wood and aluminum mini-bars that were submerged in natural waters was monitored for 180 days. Leachates contained both dissolved and particulate copper species. X-ray diffraction and X-ray photoelectron spectroscopy were used to determine the chemical phase of particles in the leachate. The amount of copper released was strongly dependent on water salinity, painted surface, and paint drying time. The presence of nanosized Cu2O particles was confirmed in paint and its leachate using single-particle inductively coupled plasma-mass spectrometry and electron microscopy. Toxicity of paint leachate to a marine phytoplankton was also evaluated. PMID- 27393963 TI - Fate of NDMA precursors through an MBR-NF pilot plant for urban wastewater reclamation and the effect of changing aeration conditions. AB - The removal of N-nitrosodimethylamine (NDMA) formation potential through a membrane bioreactor (MBR) coupled to a nanofiltration (NF) pilot plant that treats urban wastewater is investigated. The results are compared to the fate of the individual NDMA precursors detected: azithromycin, citalopram, erythromycin, clarithromycin, ranitidine, venlafaxine and its metabolite o desmethylvenlafaxine. Specifically, the effect of dissolved oxygen in the aerobic chamber of the MBR pilot plant on the removal of NDMA formation potential (FP) and individual precursors is studied. During normal aerobic operation, implying a fully nitrifying system, the MBR was able to reduce NDMA precursors above 94%, however this removal percentage was reduced to values as low as 72% when changing the conditions to minimize nitrification. Removal decreased also for azithromycin (68-59%), citalopram (31-17%), venlafaxine (35-15%) and erythromycin (61-16%) on average during nitrifying versus non-nitrifying conditions. The removal of clarithromycin, o-desmethylvenlafaxine and ranitidine could not be correlated with the nitrification inhibition, as it varied greatly during the experiment time. The MBR pilot plant is coupled to a nanofiltration (NF) system and the results on the rejection of both, NDMA FP and individual precursors, through this system was above 90%. Finally, results obtained for the MBR pilot plant are compared to the percentage of removal by a conventional full scale biological wastewater treatment plant (WWTP) fed with the same influent. During aerobic operation, the removal of NDMA FP by the MBR pilot plant was similar to the full scale WWTP. PMID- 27393964 TI - Impact of chlorine on the cell integrity and toxin release and degradation of colonial Microcystis. AB - The occurrence of toxic cyanobacteria in drinking water sources is problematic for water authorities as they can impair drinking water quality. Chlorine as a commonly used oxidant in water treatment plants has shown the potential to lyse cyanobacterial cells, resulting in the release of secondary metabolites which are hard to be removed during conventional water treatment processes. The majority of cyanobacterial species such as Microcystis, often occur in colonial forms under natural conditions. However, previous studies have mainly focused on the influence of chlorination on individual cyanobacterial cells due to technique limitations. A syringe dispersion method combined with a fluorescence technique (SYTOX Green stain with flow cytometry), was successfully developed for the evaluation of cell integrity of colonial Microcystis. Chlorination of Microcystis laden water was conducted at different chlorine dosages for different colonial sizes (<37, 37-270 and 270-550 MUm). The results indicated that colonial Microcystis cells were more resistant to chlorine oxidation than individual cells, which may be attributed to protection from the cell-bound mucilage. There was a lag phase before cell rupture occurred and a Delayed Chick Watson Model describes the experimental data very well for the kinetics of cyanobacterial cell rupture. The growing colonial size caused increases in the lag phases but decreases in the cell lysis rates. Chlorination also induced the release of microcystins (MCs) from colonial Microcystis cells. In particular, increased levels of dissolved MCs were observed in Cheng Kung Lake (CKL) water. In summary, the reaction of chlorine with colonial cyanobacteria is more complicated than with individual cells. The efficiency of chlorine oxidation could be reduced by the cell-bound mucilage and natural water matrix. These observations may provide insights for water authorities to assess the risk to drinking water quality posed by chlorination under natural conditions. PMID- 27393965 TI - Effects of halide ions on photodegradation of sulfonamide antibiotics: Formation of halogenated intermediates. AB - The occurrence of sulfonamide antibiotics (SAs) in estuarine waters urges insights into their environmental fate for ecological risk assessment. Although many studies focused on the photochemical behavior of SAs, yet the effects of halide ions relevant to estuarine and marine environments on their photodegradation have been poorly understood. Here, we investigated the effects of halide ions on the photodegradation of SAs with sulfapyridine, sulfamethazine, and sulfamethoxazole as representative compounds. Results showed that halide ions did not significantly impact the photodegradation of sulfapyridine and sulfamethoxazole, while they significantly promoted the photodegradation of sulfamethazine. Further experiments found that ionic strength applied with NaClO4 significantly enhanced the photodegradation of the SAs, which was attributed to the decreased quenching rate constant of the triplet-excited SAs ((3)SA(*)). Compared with ionic strength, specific Cl(-) effects retarded the photodegradation of the SAs. Our study found that triplet-excited sulfamethazine can oxidize halide ions to produce halogen radicals, subsequently leading to the halogenation of sulfamethazine, which was confirmed by the identification of both chlorinated and brominated intermediates. These results indicate that halide ions play an important role in the photochemical behavior of some SAs in estuarine waters and seawater. The occurrence of halogenation for certain organic pollutants can be predicted by comparing the oxidation potentials of triplet excited contaminants with those of halogen radicals. Our findings are helpful in understanding the photochemical behavior and assessing the ecological risks of SAs and other organic pollutants in estuarine and marine environment. PMID- 27393966 TI - Using density functional theory to study shape-reactivity relationships in Keggin Al-nanoclusters. AB - Keggin-based aluminum nanoclusters have been shown to be efficient sorbents for the removal of arsenic from water. Obtaining a molecular-level understanding of the adsorption processes associated with these molecules is of fundamental importance, and could pave the way for rational design strategies for water treatment. Due to their size and the availability of experimental crystal structures, Al nanoclusters are computationally tractable at the density functional theory (DFT) level. Here, we compare the reactivity of three aluminum polycations: [Al13O4(OH)24(H2O)12](7+) (Al13), [Al30O8(OH)56(H2O)26](18+) (Al30), and [Al32O8(OH)60(H2O)30](20+) (Al32). We use DFT calculations to determine reactivity as a function of particle topography, using sulfate and chloride as adsorption probes. Our comparative modeling of outer-sphere adsorption of Cl(-) and SO4(2-) on Al13, Al30, and A132 supports that the unique "hourglass" shape characteristic to Al30 gives rise to relatively strong adsorption in the molecular beltway, as well as a wide range of reaction energies as a function of particle topography. PMID- 27393967 TI - Transformation of humic acid and halogenated byproduct formation in UV-chlorine processes. AB - The synergistic effect of ultraviolet light (UV) and chlorine on the structural transformation of Humic Acid (HA) and formation of chloro-disinfection byproducts (DBPs) in water were investigated, with chlorination as a reference. The transformation and mineralization of HA were enhanced upon co-exposure to UV and chlorine. Electron spin resonance (ESR) studies revealed that hydroxyl radical (OH) and chlorine radical (Cl) were predominant active species in a pH range from 4 to 7, while Cl dominated at pH 2 and pH higher than 7. The impact of different radicals on the transformation of HA was investigated by UV254, fluorescence and TOC measurements. OH were found to be responsible for the removal of chromophoric groups and mineralization of HA, while Cl mainly reacted with HA and intermediates from HA degradation. Due to the competitive and synergistic reaction of OH and Cl with HA, higher removal of HA and lower formation of chloro DBPs appeared in UV-chlorine than chlorination, thus the combined UV-chlorine processes should be a promising method for water purification. PMID- 27393968 TI - Identification of nitrosamine precursors from urban drainage during storm events: A case study in southern China. AB - The drinking water sources of many cities in southern China are frequently contaminated by upstream urban drainage during storm events, which brings high concentrations of N-nitrosamine (NA) precursors and poses a threat to the safety of drinking water. We conducted two sampling campaigns during the heavy rain season in 2015 in one representative city in southern China. We detected that the concentration of N-nitrosodimethylamine formation potential (NDMA FP) in urban drainage during two storm events was 80-115 ng/L and the total formation potential concentration of nine nitrosamines (TNA9 FP) was 145-165 ng/L. To address the deteriorated water quality, 30 mg/L of powdered activated carbon (PAC) was fed into the water intake. PAC adsorption alone could remove 52% of NDMA FP and 52% of TNA FP, while the subsequent conventional process only removed 8% of TNA FP. We isolated six chemicals (N,N-benzyldimethylamine, 5 [(dimethylamino)methyl]-2-furanmethanol, N,N-dimethyl-3-aminophenol, N,N dimethylethylamine, Ziram, and N,N-dimethylaniline) and confirmed them to be NA precursors. Among these NA precursors, Ziram was identified for the first time as a NA precursor that is formed via chloramination; its molar yield for NDMA was 6.73 +/- 0.40%. PMID- 27393969 TI - Highly efficient removal of chromium(VI) by Fe/Ni bimetallic nanoparticles in an ultrasound-assisted system. AB - Highly active Fe/Ni bimetallic nanocomposites were prepared by using the liquid phase reduction method, and they were proven to be effective for Cr(VI) removal coupled with US irradiation. The US-assisted Fe/Ni bimetallic system could maintain a good performance for Cr(VI) removal at a wide pH range of 3-9. Based on the characterization of the Fe/Ni nanoparticles before and after reaction, the high efficiency of the mixed system could attribute to the synergistic effects of the catalysis of Ni(0) and US cavitation. Ni(0) could facilitate the Cr(VI) reduction through electron transfer and catalytic hydrogenation. Meanwhile, US could fluidize the Fe/Ni nanoparticles to increase the actual reactive surface area and clean off the co-precipitated Fe(III)-Cr(III) hydroxides to maintain the active sites on the surface of the Fe/Ni nanoparticles. Thus, compared with shaking, the US-assisted Fe/Ni system was more efficient on Cr(VI) removal, which achieved 94.7% removal efficiency of Cr(VI) within 10 min. The pseudo-first-order rate constant (kobs) in US-assisted Fe/Ni system (0.5075 min(-1)) was over 5 times higher than that under shaking (0.0972 min(-1)). Moreover, the Fe/Ni nanoparticles still have a good performance under US irradiation after 26 days aging as well as regeneration. PMID- 27393970 TI - Comparison of chromium III and VI toxicities in water using sulfur-oxidizing bacterial bioassays. AB - The toxicities of Cr (III) and Cr (VI) in water were evaluated using sulfur oxidizing bacterial (SOB) bioassays both in batch and fed-batch conditions. Two days were enough for a quick buildup of SOB consortium in the master culture reactor (MCR). At concentrations up to 100 mg L(-1), Cr (III) was found to be nontoxic in both conditions, while Cr (VI) at very low concentrations (0.1-2 mg L(-1)) was very toxic to the SOB. Literature review suggested that the nontoxic nature of Cr (III) might be due to the absence of the iron uptake pathway in Acidithiobacillus caldus (the predominant bacteria in our reactors), which is required for Cr (III) uptake. The 2-h median effective concentration (EC50) values obtained for Cr (VI) in the batch and fed-batch tests were 2.7 mg L(-1) and 1.5 mg L(-1), respectively. PMID- 27393971 TI - Oral imazalil exposure induces gut microbiota dysbiosis and colonic inflammation in mice. AB - The fungicide imazalil (IMZ) is used extensively in vegetable and fruit plantations and as a post-harvest treatment to avoid rot. Here, we revealed that ingestion of 25, 50 and 100 mg IMZ kg(-1) body weight for 28 d induced gut microbiota dysbiosis and colonic inflammation in mice. The relative abundance of Bacteroidetes, Firmicutes and Actinobacteria in the cecal contents decreased significantly after exposure to 100 mg kg(-1) IMZ for 28 d. In feces, the relative abundance in Bacteroidetes, Firmicutes and Actinobacteria decreased significantly after being exposed to 100 mg kg(-1) IMZ for 1, 14 and 7 d, respectively. High throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant reduction in the richness and diversity of microbiota in cecal contents and feces of IMZ-treated mice. Operational taxonomic units (OTUs) analysis identified 49.3% of OTUs changed in cecal contents, while 55.6% of OTUs changed in the feces after IMZ exposure. Overall, at the phylum level, the relative abundance of Firmicutes, Proteobacteria and Actinobacteria increased and that of Bacteroidetes decreased in IMZ-treated groups. At the genus level, the abundance of Lactobacillus and Bifidobacterium decreased while those of Deltaproteobacteria and Desulfovibrio increased in response to IMZ exposure. In addition, it was observed that IMZ exposure could induce colonic inflammation characterized by infiltration of inflammatory cells, elevated levels of lipocalin 2 (lcn-2) in the feces, and increased mRNA levels of Tnf-alpha, IL-1beta, IL-22 and IFN-gamma in the colon. Our findings strongly suggest that ingestion of IMZ has some risks to human health. PMID- 27393972 TI - The intraflagellar transport machinery in ciliary signaling. AB - Cilia and flagella on eukaryotic cells are slender microtubule-based projections surrounded by a membrane with a unique lipid and protein composition. It is now appreciated that cilia in addition to their established roles in motility also constitute hubs for cellular signaling by sensing external environmental cues necessary for organ development and maintenance of human health. Pathways reported to rely on the cilium organelle include Hedgehog, TGF-beta, Wnt, PDGFRalpha, integrin and DNA damage repair signaling. An emerging theme in ciliary signaling is the requirement for active transport of signaling components into and out of the cilium proper. Here, we review the current state-of-the-art regarding the importance of intraflagellar transport and BBSome multi-subunit complexes in ciliary signaling. PMID- 27393973 TI - New insight into cofactor-free oxygenation from combined experimental and computational approaches. AB - Molecular oxygen (O2), in spite being a potentially strong oxidant, typically displays very poor reactivity with organic molecules. This is largely due to quantum chemical reasons as O2 in its ground state is a diradical (3O2) whilst common organic substrates are in a singlet state. For this reason catalysis involving O2 as a reactant is typically mediated by enzymes containing redox metal and/or organic co-factors. Cofactor-independent oxygenases (and oxidases) are therefore intriguing enzymes from a fundamental viewpoint. This review looks at recent advances that have been made in understanding of this class of intriguing biocatalysts highlighting the power of an inter-disciplinary approach involving structural biology, spectroscopy and theoretical methods. PMID- 27393974 TI - Inherent properties not conserved in other tenuiviruses increase priming and realignment cycles during transcription of Rice stripe virus. AB - Two tenuiviruses Rice stripe virus (RSV) and Rice grassy stunt virus (RGSV) were found to co-infect rice with the same reovirus Rice ragged stunt virus (RRSV). During the co-infection, both tenuiviruses recruited 10-21 nucleotides sized capped-RNA leaders from the RRSV. A total of 245 and 102 RRSV-RGSV and RRSV-RSV chimeric mRNA clones, respectively, were sequenced. An analysis of the sequences suggested a scenario consistent with previously reported data on related viruses, in which capped leader RNAs having a 3' end complementary to the viral template are preferred and upon base pairing the leaders prime processive transcription directly or after one to several cycles of priming and realignment (repetitive prime-and-realign). Interestingly, RSV appeared to have a higher tendency to use repetitive prime-and-realign than RGSV even with the same leader derived from the same RRSV RNA. Combining with relevant data reported previously, this points towards an intrinsic feature of RSV. PMID- 27393976 TI - [Not Available]. PMID- 27393975 TI - A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides). AB - We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cutavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined. PMID- 27393977 TI - [Not Available]. PMID- 27393978 TI - [At-home nursing care, challenges and perspectives]. AB - Private practice nursing is evolving in line with the major mutations taking place within French society and the health system. These evolutions require nurses to adapt to significant changes. Their clinical, cultural and organisational skills, in particular, enable them to face up to these challenges and to anticipate in order to be able to provide the best possible care in future. Private practice nursing could thereby become a speciality in its own right based on the World Health Organization's model of a "family health nurse". PMID- 27393979 TI - [The shift towards ambulatory care, from wishful thinking to practice]. AB - For several years, there has been a distinct political will for the development of home care. However, this shift to ambulatory care, a source of financial savings for the health system and comfort for the patient, requires sociological debate. Notable issues for discussion are the social inequalities caused by this evolution and the role of the family in the care. PMID- 27393980 TI - [Telling the truth to the patient and their family, an ethical challenge]. AB - Nursing practice encounters a number of areas of uncertainty which are not entirely assuaged by the legal framework or best practice recommendations. Caregivers must demonstrate lucidity and sincerity, with regard to themselves and their patients, and undertake humanist and ethical reflection. Announcing a serious diagnosis is the first difficult stage of a complicated and painful experience, shared between the patient, the family or institutional carers and the health professionals. PMID- 27393981 TI - [Ethical questioning with an elderly couple losing their autonomy at home]. AB - The complexity of the situation of certain patients living at home can place health professionals in a difficult position. Inter-professional collaboration, in consultation with the patient and their relatives, is essential to ensure a patient can remain at home and to adopt an ethical approach in all circumstances. PMID- 27393982 TI - [Support of a network to favour end-of-life care at home]. AB - At-home palliative care requires efficient collaboration between all the relevant healthcare professionals. The palliative care network helps to coordinate these teams. It supports professionals to assure the continuity of care, the implementation of living wills and the availability of the medicines necessary to relieve patients' discomfort or pain at the end of life. PMID- 27393983 TI - [Not Available]. PMID- 27393984 TI - [The coordination of caregivers in the patient's home]. AB - Home care is provided by different partners who may be self-employed in private practice, part of an association or employed by the hospital. For optimal patient management, all these caregivers, whatever their role, must collaborate while respecting the work of each individual. This collective consciousness requires the reorganisation of our care system to improve efficiency. Communication between everyone is essential. PMID- 27393985 TI - [Private practice nursing, reacting in emergency situations. Private practice nursing, reacting in emergency situations]. AB - Private practice professionals providing care in patients' homes are often isolated. The care is controlled by a multidisciplinary care network. In the event of a life-threatening emergency, the Aide Medicale Urgente control centre activates if necessary the rapid intervention of emergency services. An accurate assessment, the anticipation of an emergency transfer to hospital and knowledge of the regulatory framework ensure the patient is handled efficiently and respectfully. PMID- 27393986 TI - [Not Available]. PMID- 27393987 TI - [The importance of continuing training in the field of home care]. AB - When delivering care in the patient's home, the nurse is often alone. Care procedures are becoming increasingly complex in contexts which are often mentally challenging. It is essential that nurses regularly update their knowledge through continuing training sessions in order to maintain their skills. PMID- 27393988 TI - [Maintaining the proper distance for nurses working in the home]. AB - Health professionals must be able to respond to many different situations which require technical knowledge and self-control. Particularly when working in the patient's home, nurses must know how to maintain a proper distance to protect themselves from burnout. In this respect, the practice analysis constitutes an adapted support tool. PMID- 27393989 TI - [Supervising student nurses in the provision of home care]. AB - The private practice nurse may be required to supervise a student during their provision of care to patients in their home. These situations can be mutually rewarding and open the way for discussion around the quality of care. PMID- 27393990 TI - [Not Available]. PMID- 27393991 TI - Genome-wide characterization of pectin methyl esterase genes reveals members differentially expressed in tolerant and susceptible wheats in response to Fusarium graminearum. AB - Pectin methyl esterase (PME) genes code for enzymes that are involved in structural modifications of the plant cell wall during plant growth and development. They are also involved in plant-pathogen interaction. PME genes belong to a multigene family and in this study we report the first comprehensive analysis of the PME gene family in bread wheat (Triticum aestivum L.). Like in other species, the members of the TaPME family are dispersed throughout the genome and their encoded products retain the typical structural features of PMEs. qRT-PCR analysis showed variation in the expression pattern of TaPME genes in different tissues and revealed that these genes are mainly expressed in flowering spikes. In our attempt to identify putative TaPME genes involved in wheat defense, we revealed a strong variation in the expression of the TaPME following Fusarium graminearum infection, the causal agent of Fusarium head blight (FHB). Particularly interesting was the finding that the expression profile of some PME genes was markedly different between the FHB-resistant wheat cultivar Sumai3 and the FHB-susceptible cultivar Bobwhite, suggesting a possible involvement of these PME genes in FHB resistance. Moreover, the expression analysis of the TaPME genes during F. graminearum progression within the spike revealed those genes that responded more promptly to pathogen invasion. PMID- 27393992 TI - Physiological and biochemical characterization of two Amaranthus species under Cr(VI) stress differing in Cr(VI) tolerance. AB - The present study was undertaken to evaluate Cr(VI) toxicity tolerance in two Amaranthus species viz. Amaranthus viridis and Amaranthus cruentus exposed to hexavalent chromium [Cr(VI)] stress. To ascertain this, both Amaranthus species were grown under various concentrations (0, 10 and 50 MUM) of Cr(VI) in the hydroponic system. After 7 days of Cr(VI) treatment, various traits such as growth, Cr accumulation, photochemistry of photosystem II (PS II) (JIP-test), oxidative stress and antioxidant defense system were analyzed. Cr(VI) treatments caused inhibition in growth and PS II photochemistry, which was accompanied with increased accumulation of Cr that results into enhanced generation of reactive oxygen species (ROS): O2- and H2O2, which subsequently induced the peroxidation of lipids and leakage of electrolyte in both the Amaranthus species. Cr(VI) accumulation, lipid peroxidation and electrolyte leakage were more pronounced in A. viridis than in A. cruentus. On the other hand, A. cruentus seedlings showed higher activities of enzymatic antioxidants: SOD, POD, CAT and GST, and non enzymatic antioxidants: cysteine and non-protein thiols (NP-SH) levels than A. viridis. The overall results suggest that A. cruentus is more tolerant than A. viridis due to its higher antioxidant defense system that protected seedlings under Cr(VI) stress. PMID- 27393993 TI - A Serine/threonine kinase PknL, is involved in the adaptive response of Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis adapts itself to various environmental stress conditions to thrive inside the phagosome for establishing a chronic infection. Serine/threonine protein kinases (STPKs) play a major role in the physiology and pathogenesis of Mycobacterium tuberculosis. Some of these STPKs are involved in regulating the growth of the mycobacterium under nutrient stress and starvation conditions. In this study, we have investigated the role of PknL, a STPK in the adaptive responses of M. tuberculosis by conditional inactivation of the gene using antisense technology. The inhibition of PknL in the knockdown strain was validated by RT-PCR. The in vitro growth kinetics of M. tuberculosis strain following inhibition of PknL was found to be bacteriostatic. The knock down strain of PknL exhibited a better survival in pH 5.5 when compared to its growth in pH 7.0. Similarly, it also exhibited more resistance to both SDS(0.01%) and Lysozyme stress (2.5mg/ml), indicating that loss of PknL enhances the growth of mycobacterium under stress conditions. SEM pictographs also represent an increase in the cell length of the knock down strain compared to Wild type stressing its role in cellular integrity. Lastly, the proteome analysis of differentially expressing PknL strains by 2D gel electrophoresis and mass spectrometry identified 19 differentially expressed proteins. Our findings have shown that PknL plays an important role in sensing the host environment and adapting itself in slowing down the growth of the pathogen and persisting within the host. PMID- 27393994 TI - Illumina-based analysis of core actinobacteriome in roots, stems, and grains of rice. AB - Seed-borne microbiota can transmit vertically from generation to generation and be a favour mutualism between the endosymbionts and hosts. The aim of this study was to investigate the rice-associated actinobacterial taxa in roots, stems, and grains and explore vertically transmitted core actinobacteriome of rice plants. Illumina sequencing analyses of samples of rice grains, stems, and roots showed that the roots contained the most diverse actinobacteria among the tissues. The grains contained 78 actinobacterial operational taxonomic units (OTUs), among which 44 were shared with those in the stems, 30 shared with those in the roots. The coexisted OTUs in the three types of samples mainly belong to genera of Pseudonocardia, Dietzia, Nocardioides, Streptomyces, Mycobacterium, Corynebacterium, Citricoccus, Salinibacterium, and Agrococcus, and other unclassified taxa. The dominant actinobacterial genera Pseudonocardia and Dietzia in the stems and roots were still detected in relatively high abundance in the grains. The Streptomyces isolated from surface sterilized grains could improve nitrogen use efficiency of rice seedlings and the resistance to rice blast fungus. The results suggested that the rice grains contained diverse actinobacterial taxa deriving from stems and roots and showed intimate correlation with the host plants. PMID- 27393995 TI - Evaluation of acrylamide-removing properties of two Lactobacillus strains under simulated gastrointestinal conditions using a dynamic system. AB - The aim of this study was to evaluate the capability of Lactobacillus reuteri NRRL 14171 and Lactobacillus casei Shirota to remove dietary acrylamide (AA) under simulated gastrointestinal conditions using a dynamic system. The effects of different AA levels or bacteria concentration on toxin removal by Lactobacillus strains were assessed. Thereafter, AA-removing capability of bacteria strains under either fasting or postprandial simulated gastrointestinal conditions was evaluated. Commercial potato chips were analyzed for their AA content, and then used as a food model. Average AA content (34,162MUg/kg) in potato chips exceeded by ca. 34-fold the indicative values recommended by the EU. Toxin removal ability was dependent on AA content and bacterial cell concentration. A reduction on bacterial viability was observed in the food model and at the end of both digestive processes evaluated. However, bacteria survived in enough concentrations to remove part of the toxin (32-73%). Both bacterial strains were able to remove AA under different simulated gastrointestinal conditions, being L. casei Shirota the most effective (ca. 70% removal). These findings confirmed the risk of potato chips as dietary AA exposure for consumers, and that strains of the genus Lactobacillus could be employed to reduce the bioavailability of dietary AA. PMID- 27393996 TI - Binding of a proline-independent hydrophobic motif by the Candida albicans Rvs167 3 SH3 domain. AB - Src-homology 3 (SH3) domains are small protein-protein interaction modules. While most SH3 domains bind to proline-x-x-proline (PxxP) containing motifs in their binding partners, some SH3 domains recognize motifs other than proline-based sequences. Recently, we showed that the SH3 domain of Candida albicans Rvs167-3 binds peptides enriched in hydrophobic residues and containing a single proline residue (RPhixPhixPhiP, where x is any amino acid and Phi is a hydrophobic residue). Here, we demonstrate that the proline in this motif is not required for Rvs167-3 SH3 recognition. Through mutagenesis studies we show that binding of the peptide ligand involves the conserved tryptophan in the canonical PxxP binding pocket as well as residues in the extended n-Src loop of Rvs167-3 SH3. Our studies establish a novel, proline-independent, binding sequence for Rvs167-3 SH3 (RPhixPhixPhi) that is comprised of a positively charged residue (arginine) and three hydrophobic residues. PMID- 27393997 TI - Phenol degradation by Sulfobacillus acidophilus TPY via the meta-pathway. AB - Due to its toxicity and volatility, phenol must be cleared from the environment. Sulfobacillus acidophilus TPY, which was isolated from a hydrothermal vent in the Pacific Ocean as a moderately thermoacidophilic Gram-positive bacterium, was capable of aerobically degrading phenol. This bacterium could tolerate up to 1300mg/L phenol and degrade 100mg/L phenol in 40h completely at 45 degrees C and pH 1.8 with a maximal degradation rate of 2.32mg/L/h at 38h. Genome-wide search revealed that one gene (TPY_3176) and 14 genes clustered together in two regions with locus tags of TPY_0628-0634 and TPY_0640-0646 was proposed to be involved in phenol degradation via the meta-pathway with both the 4-oxalocrotonate branch and the hydrolytic branch. Real-time PCR analysis of S. acidophilus TPY under phenol cultivation condition confirmed the transcription of proposed genes involved in the phenol degradation meta-pathway. Degradation of 3-methylphenol and 2 methylphenol confirmed that the hydrolytic branch was utilised by S. acidophilus TPY. Phylogenetic analysis revealed that S. acidophilus TPY was closely related to sulphate-reducing bacteria and some Gram-positive phenol-degrading bacteria. This was the first report demonstrating the ability of S. acidophilus to degrade phenol and characterising the putative genes involved in phenol metabolism in S. acidophilus TPY. PMID- 27393998 TI - Bacteria as growth-promoting agents for citrus rootstocks. AB - The microbial community plays an essential role in maintaining the ecological balance of soils. Interactions between microorganisms and plants have a major influence on the nutrition and health of the latter, and growth-promoting rhizobacteria can be used to improve plant development through a wide range of mechanisms. Therefore, the objective of the present study was to evaluate bacteria as growth-promoting agents for citrus rootstocks. A total of 30 bacterial isolates (11 of Bacillus spp., 11 actinobacteria, and 8 lactic acid bacteria) were evaluated in vitro for indoleacetic acid production, phosphate solubilization, and nitrogen (N) fixation. In vivo testing consisted of growth promotion trials of the bacterial isolates that yielded the best results on in vitro tests with three rootstocks: Swingle citrumelo [Citrus*paradisi Macfad cv. Duncan*Poncirus trifoliata (L.) Raf.], Sunki mandarin (Citrus sunki Hort. ex Tan), and rangpur (Citrus*limonia Osbeck). The parameters of interest were height, number of leaves, stem diameter, shoot and root dry mass, and total dry mass at 150days after germination. The results showed that most bacterial isolates were capable of IAA production. Only one lactic acid bacterium isolate (BL06) solubilized phosphate, with a high solubilization index (PSI>3). In the actinobacteria group, isolates ACT01 (PSI=2.09) and ACT07 (PSI=2.01) exhibited moderate phosphate-solubilizing properties. Of the Bacillus spp. isolates, only CPMO6 and BM17 solubilized phosphate. The bacterial isolates that most fixated nitrogen were BM17, ACT11, and BL24. In the present study, some bacteria were able to promote growth of citrus rootstocks; however, this response was dependent on plant genotype and isolate. Bacillus spp. BM16 and CPMO4 were able to promote growth of Swingle citrumelo. In Sunki mandarin plants, the best treatment results were obtained with BM17 (Bacillus sp.) and ACT11 (actinobacteria). For Rangpur lime rootstock, only BM05 (Bacillus sp.) was able to promote increase in two parameters assessed, height and number of leaves. When the bacterial isolates were used in mixture there was not promoted growth of plants on rootstocks. This fact may be associated with the different mechanisms of action of each bacteria involved or with the presence of competition among the microorganisms of the mixture. PMID- 27393999 TI - In Azospirillum brasilense, mutations in flmA or flmB genes affect polar flagellum assembly, surface polysaccharides, and attachment to maize roots. AB - Azospirillum brasilense is a soil bacterium capable of promoting plant growth. Several surface components were previously reported to be involved in the attachment of A. brasilense to root plants. Among these components are the exopolysaccharide (EPS), lipopolysaccharide (LPS) and the polar flagellum. Flagellin from polar flagellum is glycosylated and it was suggested that genes involved in such a posttranslational modification are the same ones involved in the biosynthesis of sugars present in the O-antigen of the LPS. In this work, we report on the characterization of two homologs present in A. brasilense Cd, to the well characterized flagellin modification genes, flmA and flmB, from Aeromonas caviae. We show that mutations in either flmA or flmB genes of A. brasilense resulted in non-motile cells due to alterations in the polar flagellum assembly. Moreover, these mutations also affected the capability of A. brasilense cells to adsorb to maize roots and to produce LPS and EPS. By generating a mutant containing the polar flagellum affected in their rotation, we show the importance of the bacterial motility for the early colonization of maize roots. PMID- 27394000 TI - A phenazine-1-carboxylic acid producing polyextremophilic Pseudomonas chlororaphis (MCC2693) strain, isolated from mountain ecosystem, possesses biocontrol and plant growth promotion abilities. AB - The genus Pseudomonas is known to comprise a huge diversity of species with the ability to thrive in different habitats, including those considered as extreme environments. In the present study, a psychrotolerant, wide pH tolerant and halotolerant strain of Pseudomonas chlororaphis GBPI_507 (MCC2693), isolated from the wheat rhizosphere growing in a mountain location in Indian Himalayan Region (IHR), has been investigated for its antimicrobial potential with particular reference to phenazine production and plant growth promoting traits. GBPI_507 showed phenazine production at the temperatures ranged from 14 to 25 degrees C. The benzene extracted compound identified as phenazine-1-carboxylic acid (PCA) through GC-MS exhibited antimicrobial properties against Gram positive bacteria and actinomycetes. The inhibition of phytopathogens in diffusible biocontrol assays was recorded in an order: Alternaria alternata>Phytophthora sp.>Fusarium solani>F. oxysporum. In volatile metabolite assays, all the pathogens, except Phytophthora sp. produced distorted colonies, characterized by restricted sporulation. The isolate also possessed other growth promoting and biocontrol traits including phosphate solubilization and production of siderophores, HCN, ammonia, and lytic enzymes (lipase and protease). Molecular studies confirmed production of PCA by the bacterium GBPI_507 through presence of phzCD and phzE genes in its genome. The polyextremophilic bacterial strain possesses various important characters to consider it as a potential agent for field applications, especially in mountain ecosystem, for sustainable and eco-friendly crop production. PMID- 27394001 TI - Effects of crop viruses on wild plants. AB - Global land conversion and intensification of agriculture mean that remnant native plant populations are increasingly exposed to crop viruses. What are the consequences for wild plants? In natural unmanaged systems, the key consideration is how crop virus infection influences plant fitness. Field studies of virus effects on wild plant fitness are scant. Approaches include (i) observational studies, (ii) studies of experimental plants with natural infection, and (iii) studies of experimental plants with experimental infection, with most studies focused on viruses in the Luteoviridae and Potyviridae families. Fitness effects documented are largely neutral to negative. Crop virus influence on wild plants merits attention in ecological conservation and restoration. PMID- 27394002 TI - Perillyl alcohol efficiently scavenges activity of cellular ROS and inhibits the translational expression of hypoxia-inducible factor-1alpha via mTOR/4E-BP1 signaling pathways. AB - Perillyl alcohol (POH) is a dietary monoterpene present in a variety of plants with a pure or mixed form, and it is one of the very few natural substances with anticancer activity. However, the mechanism by which POH unleashes its anticancer activity in tumor cells remains unclear. We here demonstrated the effect of POH on hypoxia-inducible factor-1alpha (HIF-1alpha) activation. POH showed the potent inhibitory activity against HIF-1 activation induced by hypoxia in various human cancer cell lines and efficient scavenging activity of cellular Reactive oxygen species (ROS) by hypoxia in tumor cells. Further analysis revealed that POH inhibited HIF-1alpha protein synthesis, without affecting the expression level of HIF-1alpha mRNA or degradation of HIF-1alpha protein. Moreover, we found that suppression of HIF-1alpha accumulation by POH correlated with strong de phosphorylation of mammalian target of rapamycin (mTOR) and eIF4E binding protein 1 (4E-BP1), and eukaryotic initiation factor 4E (eIF4E). These results showed that POH inhibited HIF-1alpha protein synthesis through the inhibition of mTOR/4E BP1 signaling pathways. Furthermore, POH increased the expression of p53, p21, induced cell cycle arrest in the G1 phase as well as decreased cyclin D1, c-Myc, and Skp2 expression. In vivo studies further confirmed the inhibitory effect of POH on the expression of HIF-1alpha proteins, leading to a decrease growth of HCT116 cells in a xenograft tumor model. There results show that POH is an effective inhibitor of HIF-1 and provide new perspectives in to the mechanism of its anticancer activity. PMID- 27394003 TI - Association of HLA-DP/DQ and STAT4 polymorphisms with ankylosing spondylitis in Southwest China. AB - Ankylosing spondylitis (AS) is a highly heritable complex inflammatory arthritis disease. Genetic factors are thought to be crucial in the pathogenesis of AS. However, few data are available on the relationship between HLA-DP/DQ and STAT4 polymorphisms and AS susceptibility in the Chinese population. Therefore, we examined HLA-DP/DQ and STAT4 polymorphisms (rs3077, rs9277535, rs7453920 and rs7574865) in a total of 779 subjects, including 400 AS and 379 age- and sex matched healthy controls in Chinese. No significant difference was observed between AS patients and healthy controls in the allele frequency of rs3077, rs9277535 and rs7574865. However, there was a significant association between the HLA-DQ rs7453920 G/A variant and AS patients, with minor allele A correlated with a reduced risk of AS (allelic frequency, adjusted OR=0.66, 95% CI=0.55-0.78, p=4.0E-06; dominant model, adjusted OR=0.75, 95% CI=0.66-0.85, p=1.1E-05). Moreover, the haplotypes block AAA and GGA in the HLA gene significantly correlated with reduced risk of AS. This is the first study demonstrating the significant associations of SNP rs7453920 and the haplotypes in the HLA gene with the risk of AS in Southwest Chinese population. This research sheds new light on the significant relationship between HLA polymorphisms and AS. PMID- 27394004 TI - Analysis of sulfate metabolites of the doping agents oxandrolone and danazol using high performance liquid chromatography coupled to tandem mass spectrometry. AB - The direct detection of sulfate conjugates of anabolic androgenic steroids (AAS) can be a powerful tool in doping control analysis. By skipping the solvolysis step analysis time can be reduced, and due to long term sulfate metabolites the detection time can be significantly extended as demonstrated for some AAS. This study presents the successful identification of sulfate metabolites of the doping agents oxandrolone and danazol in excretion urines by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The sulfate conjugate of 17beta-hydroxymethyl-17alpha-methyl-18-nor-2-oxa-5alpha-androsta-13 en-3-one could be identified as a new metabolite of oxandrolone. Sulfate conjugates of the danazol metabolites ethisterone and 2alpha hydroxymethylethisterone were identified in an excretion urine for the first time. In addition, these sulfate conjugates were synthesized successfully. For a confirmation analysis, the number of analytes can be increased by additional sulfate conjugates of danazol metabolites (2-hydroxymethyl-1,2-dehydroethisterone and 6beta-hydroxy-2-hydroxymethylethisterone), which were also identified for the first time. The presented validation data underline the suitability of the identified sulfate conjugates for doping analysis with regard to the criteria given by the technical documents of the World Anti-Doping Agency (WADA). PMID- 27394005 TI - Paget's disease of the male breast in the 21st century: A systematic review. AB - Paget's disease of the breast is characterized by eczematous changes of the nipple-areolar complex and is associated with an underlying in situ or invasive breast carcinoma in most cases. Histologically, Paget's disease is identified by epithelial cells with abundant basophilic or amphophilic, finely granular cytoplasm with a large, centrally situated nucleus, most abundant in the lower epidermal layers. Due to the rarity of the condition among breast cancers, compounded by the rarity of breast cancer in men, understanding of the disease's presentation, course, and optimal treatment in men is largely derived from case reports and extrapolation of findings from studies in female patients. Paget's disease must be differentiated from other conditions including eczema, Bowen's disease, squamous cell carcinoma, and melanoma. Recognition of Paget's disease clinically and pathologically is critical as the superficial lesion may be the only sign of an underlying ductal carcinoma and its presence may be of prognostic significance. This article provides an update on cases of Paget's disease of the breast in men reported in the published literature together with a comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data, 1973-2012. Current understanding and management of the disease in the context of male patients is reviewed. However, additional research is required to further understand the overall pathogenesis and molecular profile of Paget's disease to provide improved insight for personalized, precision-based therapeutic options. PMID- 27394006 TI - Decision rules for allocation of finances to health systems strengthening. AB - A key dilemma in global health is how to allocate funds between disease-specific "vertical projects" on the one hand and "horizontal programmes" which aim to strengthen the entire health system on the other. While economic evaluation provides a way of approaching the prioritisation of vertical projects, it provides less guidance on how to prioritise between horizontal and vertical spending. We approach this problem by formulating a mathematical program which captures the complementary benefits of funding both vertical projects and horizontal programmes. We show that our solution to this math program has an appealing intuitive structure. We illustrate our model by computationally solving two specialised versions of this problem, with illustrations based on the problem of allocating funding for infectious diseases in sub-Saharan Africa. We conclude by reflecting on how such a model may be developed in the future and used to guide empirical data collection and theory development. PMID- 27394007 TI - Privatization and quality: Evidence from elderly care in Sweden. AB - Non-contractible quality dimensions are at risk of degradation when the provision of public services is privatized. However, privatization may increase quality by fostering performance-improving innovation, particularly if combined with increased competition. We assemble a large data set on elderly care services in Sweden between 1990 and 2009 and estimate how opening to private provision affected mortality rates - an important and not easily contractible quality dimension - using a difference-in-difference-in-difference approach. The results indicate that privatization and the associated increase in competition significantly improved non-contractible quality as measured by mortality rates. PMID- 27394008 TI - Rose bengal uptake by E. faecalis and F. nucleatum and light-mediated antibacterial activity measured by flow cytometry. AB - Antibacterial photodynamic therapy (aPDT) using rose bengal (RB) and blue-light kills bacteria through the production of reactive oxygen derivates. However, the interaction mechanism of RB with bacterial cells remains unclear. This study investigated the uptake efficiency and the antibacterial activity of blue light activated RB against Enterococcus faecalis and Fusobacterium nucleatum. Spectrophotometry and epifluorescence microscopy were used to evaluate binding of RB to bacteria. The antibacterial activity of RB after various irradiation times was assessed by flow cytometry in combination with cell sorting. Uptake of RB increased in a concentration dependent manner in both strains although E. faecalis displayed higher uptake values. RB appeared to bind specific sites located at the cellular poles of E. faecalis and at regular intervals along F. nucleatum. Blue-light irradiation of samples incubated with RB significantly reduced bacterial viability. After incubation with 10MUM RB and 240s irradiation, only 0.01% (+/-0.01%) of E. faecalis cells and 0.03% (+/-0.03%) of F. nucleatum survived after treatment. This study indicated that RB can bind to E. faecalis and F. nucleatum in a sufficient amount to elicit effective aPDT. Epifluorescence microscopy showed a yet-unreported property of RB binding to bacterial membranes. Flow cytometry allowed the detection of bacteria with damaged membranes that were unable to form colonies on agars after cell sorting. PMID- 27394009 TI - Visible light induced bactericidal and photocatalytic activity of hydrothermally synthesized BiVO4 nano-octahedrals. AB - In the present work, monoclinic bismuth vanadate (m-BiVO4) nanostructures have been synthesized via simple hydrothermal method and employed for visible light driven antimicrobial and photocatalytic activity. Morphology (octahedral) and size (200-300nm) of the m-BiVO4 are studied using transmission electron microscopy (TEM). The crystal structure of m-BiVO4 (monoclinic scheelite structure) is confirmed by high resolution-TEM (HRTEM) and X-ray diffraction (XRD) studies. The band gap of m-BiVO4 was estimated to be ca. 2.42eV through Kubelka-Munk function F(Rinfinity) using diffuse reflectance spectroscopy (DRS). Antimicrobial action of m-BiVO4 is anticipated by (i) shake flask method, (ii) MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assay for cytotoxicity. SEM analysis has been carried on Escherichia coli (E.coli) before and after treatment with nanostructure materials to reveal the mechanism underlying the antimicrobial action. Antimicrobial activity is studied as a function of m-BiVO4 concentration viz. 20, 40, 60 and 80ppm. The bacterial growth is decreased 80% to 96%, with the increase in m-BiVO4 concentration from 20ppm to 80ppm, respectively, in 2h. Photocatalytic activity and rate kinetics of m-BiVO4 nanostructures have been studied as a function of time on methylene blue (MB) dye degradation which is one of the waste products of textile industries and responsible for water pollution. PMID- 27394010 TI - Photocatalytic and antibacterial response of biosynthesized gold nanoparticles. AB - Increase in the bacterial resistance to available antibiotics and water contamination by different toxic organic dyes are both severe problems throughout the world. To overcome these concerns, new methodologies including synthesis of nontoxic, human friendly and efficient nanoparticles is required. These nanoparticles not even inhibit the growth of microorganisms but are also effective in the degradation of toxic organics in waste water thus providing a clean and human friendly environment. The use of plants extracts to synthesize and stabilize noble metal nanoparticles have been considered as safe, cost effective, eco-benign and green approach nowadays. In the present study, Longan fruit juice proficiently reduced ionic gold (Au(+3)) to gold nanoparticles (AuNPs) as well as mediated the stabilization of AuNPs. The antibacterial activity of AuNPs was carried out against both gram positive and gram negative bacteria using agar well diffusion method, followed by the determination of Minimum inhibitory concentration (MIC) values. AuNPs were found to have significant antibacterial activity against Escherichia coli with MIC values of 75MUg/ml while outstanding MIC values of 50MUg/ml against Staphylococcus areous and Basilus subtilus. AuNPs revealed significant photocatalytic degradation (76%) of methylene blue in time period of 55min, indicating the effective photocatalytic property of biosynthesized AuNPs (K=0.29/min, r(2)=0.95). The considerable antibacterial and photocatalytic activities of the photosynthesized AuNPs can be attributed towards their small size, spherical morphology and uniform dispersion. Our finding suggests the possible therapeutic potential of biogenic AuNPs in the development of new antibacterial agents as well as in the development of effective photocatalysts. PMID- 27394011 TI - Plasticity of young Moringa oleifera L. plants to face water deficit and UVB radiation challenges. PMID- 27394012 TI - Fourier transform infrared spectroscopy and chemometrics for the characterization and discrimination of writing/photocopier paper types: Application in forensic document examinations. AB - The aim of the present work is to explore the non-destructive application of ATR FTIR technique for characterization and discrimination of paper samples which could be helpful to give forensic aid in resolving legal cases. Twenty-four types of paper brands were purchased from local market in and around Chandigarh, India. All the paper samples were subjected to ATR-FTIR analysis from 400 to 4000cm(-1) wavenumber range. The qualitative feature and Chemometrics of the obtained spectral data are used for characterization and discrimination. Characterization is achieved by matching the peaks with standards of cellulose and inorganic fillers, a usual constituents of paper. Three different regions of IR, i.e. 400 2000cm(-1), 2000-4000cm(-1) and 400-4000cm(-1) were selected for differentiation by Chemometrics analysis. The discrimination is achieved on the basis of three principal components, i.e. PC 1, PC 2 and PC 3. It is observed that maximum discrimination was procured in the wave number range of i.e. 2000-4000cm(-1). Discriminating power was calculated on the basis of qualitative features as well, and it is found that the discrimination of paper samples was better achieved by Chemometrics analysis rather than qualitative features. The discriminating power by Chemometrics is 99.64% and which is larger as ever achieved by any group for present number of samples. The present result confirms that this study will be highly useful in forensic document examination work in the legal cases, where the authenticity of the document is challenged. The results are completely analytical and, therefore, overcome the problem encounter in traditional routine light/radiation scanning methods which are still in practice by various questioned document laboratories. PMID- 27394013 TI - Histone deacetylases differentially regulate the proliferative phenotype of mouse bone marrow stromal and hematopoietic stem/progenitor cells. AB - Mouse bone marrow stromal stem/progenitor cells (BMSCs, also known as bone marrow derived mesenchymal stem cells) and Hematopoietic Stem and Progenitor Cells (HSPCs) with differential proliferative potentials were investigated for identifying epigenetic signals that can modulate their growth. In the present study, immunodepletion of granulo-monocytic (CD11b) and erythroid (Ter119) population yielded CD11b(-)/Ter119(-) cells, capable of differentiating into chondrogenic, osteogenic and adipogenic cells. Enrichment of the CD11b(+) population by positive selection of multipotent stem/progenitor marker (CD133) yielded CD11b(+)/CD133(+) cells, efficiently differentiated into hematopoietic lineages. Molecular characterization revealed the expression of BMSC and HSPC markers in CD11b(-)/Ter119(-) and CD11b(+)/CD133(+) sorted populations, respectively. Cell expansion studies depicted a higher growth rate and percentage of proliferating cells in G2/M phase of cell cycle in BMSCs (13.9+/-2.9%) as compared with HSPCs (5.8+/-0.8%). Analysis of the HDACs gene expression revealed a differential expression pattern in BMSCs and HSPCs that modulates the cell cycle genes. Trichostatin A (TSA)-mediated HDAC inhibition led to an increased level of AcH3 and AcH4 along with cyclins B1 and D2. Chromatin immunoprecipitation revealed alleviation of HDAC2 and HDAC3 binding by TSA on cyclins B1 and D2 promoter, thereby enhancing cell proliferation. This study identifies epigenetic modulation on the proliferative potential of BMSCs and HSPCs for stem cell transplantation therapies. PMID- 27394014 TI - Host Resistance and Immune Aging. AB - Human immune system aging results in impaired responses to pathogens or vaccines. In the innate immune system, which mediates the earliest pro-inflammatory responses to immunologic challenge, processes ranging from Toll-like Receptor function to Neutrophil Extracellular Trap formation are generally diminished in older adults. Dysregulated, enhanced basal inflammation with age reflecting activation by endogenous damage-associated ligands contributes to impaired innate immune responses. In the adaptive immune system, T and B cell subsets and function alter with age. The control of cytomegalovirus infection, particularly in the T lineage, plays a dominant role in the differentiation and diversity of the T cell compartment. PMID- 27394015 TI - Clinical Features of Infection in Older Adults. AB - The impact of infectious diseases on older adults is far greater than on younger adults because of significantly higher morbidity and mortality caused by infection. The reasons for this greater impact include factors such as lower physiologic reserve due to age and chronic disease, age-related changes in host defenses, loss of mobility, higher risk for polypharmacy and adverse drug reactions, and being on drugs that increase the risk for infection (e.g., anticholinergic and other sedating medications increase the risk for pneumonia). PMID- 27394016 TI - Principles of Antimicrobial Therapy in Older Adults. AB - Antibiotic use is common in older adults, and much of it is deemed unnecessary. Complications of antibiotic use may occur as a consequence of changes in age related physiology and dosing with resulting drug toxicity and secondary infection. Knowing when it is appropriate to initiate antibiotics may help reduce unnecessary antibiotic use and prevent adverse drug events. Careful attention to antibiotic selection, dosing adjustments, and drug-drug interactions may also help prevent antibiotic-related adverse events. PMID- 27394017 TI - Bacterial Pneumonia in Older Adults. AB - Community-acquired pneumonia is common in the elderly person; its presentation in this population is often confounded by multiple comorbid illnesses, including those that result in confusion. Although severity-of-illness scoring systems might aid decision-making, clinical judgment following a careful assessment is key in deciding on the site of care and appropriate therapy. PMID- 27394018 TI - Tuberculosis in Older Adults. AB - Tuberculosis (TB) remains one of the world's most lethal infectious diseases. Preventive and control strategies among other high-risk groups, such as the elderly population, continues to be a challenge. Clinical features of TB in older adults may be atypical and confused with age-related diseases. Diagnosis and management of TB in the elderly person can be difficult; treatment can be associated with adverse drug reactions. This article reviews the current global epidemiology, pathogenesis, clinical characteristics, diagnosis, management, and prevention of Mycobacterium tuberculosis infection in community-dwelling and institutionalized aging adults. PMID- 27394019 TI - Intraabdominal Infections in Older Adults. AB - Intraabdominal infections represent a diagnostic and therapeutic challenge in the elderly population. Atypical presentations, diagnostic delays, additional comorbidities, and decreased physiologic reserve contribute to high morbidity and mortality, particularly among frail patients undergoing emergency abdominal surgery. While many infections are the result of age-related inflammatory, mechanical, or obstructive processes, infectious complications of feeding tubes are also common. The pillars of treatment are source control of the infection and judicious use of antibiotics. A patient-centered approach considering the invasiveness, risk, and efficacy of a procedure for achieving the desired outcomes is recommended. Structured communication and time-limited trials help ensure goal-concordant treatment. PMID- 27394020 TI - Infectious Diarrhea: Norovirus and Clostridium difficile in Older Adults. AB - Norovirus infection usually results in acute gastroenteritis, often with incapacitating nausea, vomiting, and diarrhea. It is highly contagious and resistant to eradication with alcohol-based hand sanitizer. Appropriate preventative and infection control measures can mitigate the morbidity and mortality associated with norovirus infection. Clostridium difficile infection is the leading cause of health care-associated diarrhea in the United States. Antibiotic use is by far the most common risk factor for C difficile colonization and infection. Appropriate preventive measures and judicious use of antibiotics can help mitigate the morbidity and mortality associated with C difficile infection. PMID- 27394021 TI - Urinary Tract Infections in the Older Adult. AB - Urinary infection is the most common bacterial infection in elderly populations. The high prevalence of asymptomatic bacteriuria in both men and women is benign and should not be treated. A diagnosis of symptomatic infection for elderly residents of long-term care facilities without catheters requires localizing genitourinary findings. Symptomatic urinary infection is overdiagnosed in elderly bacteriuric persons with nonlocalizing clinical presentations, with substantial inappropriate antimicrobial use. Residents with chronic indwelling catheters experience increased morbidity from urinary tract infection. Antimicrobial therapy is selected based on clinical presentation, patient tolerance, and urine culture results. PMID- 27394022 TI - Herpes Zoster. AB - Herpes zoster causes significant suffering owing to acute and chronic pain or postherpetic neuralgia (PHN). Varicella-zoster virus-induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities of daily living, and reduced quality of life in older adults. The optimal treatment of herpes zoster requires early antiviral therapy and careful pain management. For patients who have PHN, evidence-based pharmacotherapy using topical lidocaine patch, gabapentin, pregabalin, tricyclic antidepressants, or opiates can reduce pain burden. The live attenuated zoster vaccine is effective in reducing pain burden and preventing herpes zoster and PHN in older adults. PMID- 27394023 TI - Bone and Joint Infections in Older Adults. AB - Bone and joint infections in the elderly patient include septic native joints, osteomyelitis, and prosthetic joint infection. Infections are difficult to treat and require a team approach. Surgical debridement and intravenous antibiotics are the keys to treatment. Prosthetic joint infections often need a two-stage approach to treatment. First the infected joint is removed and the infection treated, then a second prosthetic joint is placed. Prosthetic joint infection is becoming the most common complication after joint replacement surgery. Outcomes of treatment of bone and joint infections are related to the severity of the infection and condition of the host. Because the elderly are often frail, treatment is challenging. PMID- 27394024 TI - Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults. AB - Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities. PMID- 27394025 TI - Infections in Nursing Homes: Epidemiology and Prevention Programs. AB - This review summarizes current literature pertaining to infection prevention in nursing home population including post-acute care patients and long-term care residents. Approximately 2 million infections occur each year and more than one third of older adults harbor multidrug-resistant organisms in this setting. Surveillance, hand hygiene, isolation precautions, resident and employee health programs, education, and antibiotic stewardship are essential elements of infection prevention and control programs in nursing homes. This article discusses emerging evidence suggesting the usefulness of interactive multimodal bundles in reducing infections and antimicrobial resistance, thereby enhancing safety and quality of care for older adults in nursing homes. PMID- 27394026 TI - Vaccinations for the Older Adult. AB - Vaccine response declines with age, but currently recommended vaccines are safe and effective in reducing, if not preventing, disease altogether. Over the last decade, advancements in vaccine immunogenicity, either by increasing dose or conjugating vaccines to protein, have resulted in more immunogenic vaccines that also seem more effective in reducing clinical disease both for influenza and pneumococcus. Meanwhile, there is a resurgence in incident pertussis, exceeding prevalence from five decades ago, adding older adults to a recommended target vaccination group. This article discusses currently available vaccines, in the context of current epidemiology and recommendations, for older adults. PMID- 27394027 TI - Preface. PMID- 27394028 TI - What factors support older people to increase their physical activity levels? An exploratory analysis of the experiences of PACE-Lift trial participants. AB - BACKGROUND: Physical Activity (PA) has significant health benefits for older adults, but nearly all UK over 60's are not achieving recommended levels. The PACE-Lift primary care-based walking intervention for 60-75 year-olds used a structured, theoretically grounded intervention with pedometers, accelerometers, handbooks and support from practice nurses trained in behaviour change techniques. It demonstrated an objective increase in walking at 3 and 12 months. We investigated the experiences of intervention participants who did (and did not) increase their walking, in order to explore facilitators to increased walking. METHODS: Semi-structured telephone interviews used an interview schedule with a purposive sample of 30 intervention participants, 19 who had objectively increased their walking over the previous year and 11 who had not. Interviews were audio-recorded, transcribed and coded independently by researchers to generate a thematic coding framework. RESULTS: Both groups confirmed that walking was an appropriate PA for people of 'their age'. The majority of those with increased walking participated in the trial as a couple, were positive about individualised goal-setting, developed strategies for maintaining their walking, and had someone to walk with. Non-improvers reported their attempts to increase walking were difficult because of lack of social support and were less positive about the intervention's behaviour change components. DISCUSSION: Walking is an acceptable and appropriate PA intervention for older people. The intervention's goal-setting components were important for those who increased their walking. Mutual support between partners participating as a couple and having someone to walk with also facilitated increased walking. PMID- 27394029 TI - Detection rate of blood group alloimmunization based on real-world testing practices and kinetics of antibody induction and evanescence. AB - BACKGROUND: Failure to detect non-ABO blood group alloantibodies places patients at risk for hemolytic reactions. Suboptimal alloantibody detection could result from posttransfusion testing performed too early, too late, or not at all. Testing performed too early may precede antibody induction, while testing performed too late could miss antibodies that have evanesced. Taking these factors into account, our goal was to determine the percentage of alloantibodies detected with real-world testing practices. STUDY DESIGN AND METHODS: The alloantibody detection rate in a general hospital setting was determined based on the frequency and timing of antibody testing after red blood cell (RBC) transfusions and rates of antibody induction and evanescence. Intervals to follow up testing after RBC transfusions (n = 561 RBC units in 100 random patients) were determined retrospectively. Best-fit lines and equations for antibody induction and evanescence were computed on previously published data. RESULTS: Nearly half (271/561; 48.3%) of RBC infusions had either no follow-up antibody screen or testing too soon (<30 days) after transfusion to detect alloimmunization. Of the remaining RBC units, 10.3% (58/561) had follow-up testing 30 to 112 days posttransfusion, 28.7% (161/561) were followed up at more than 112 days, and 12.7% (71/561) were tested at both 30 to 112 days and more than 112 days. By inputting these timing data into best-fit line equations for antibody induction and evanescence, we calculated an alloantibody detection rate of 31.6%. CONCLUSION: Posttransfusion antibody testing was inadequately timed for optimal alloantibody detection. Real-world compatibility testing was predicted to detect less than one-third of non-ABO antibodies, thereby exposing patients to risks of mismatched transfusion. PMID- 27394030 TI - The alkylphospholipid edelfosine shows activity against Strongyloides venezuelensis and induces apoptosis-like cell death. AB - Strongyloidiasis is widely distributed in the tropical and subtropical areas. Ivermectin is the drug of choice for the treatment. However, the concerns about relying treatment on a single drug make identification of new molecules a priority. Alkylphospholipid analogues, including edelfosine, are a group of synthetic compounds that have shown activity against some parasites. The objective was to assess the in vitro and in vivo activity of edelfosine, miltefosine, perifosine against Strongyloides venezuelensis. Moreover, apoptosis like mechanism in larvae after treatment was studied. Edelfosine displayed the highest activity and the best selectivity index (LD50=49.6 +/- 5.4MUM, SI=1.1) compared to miltefosine or perifosine. Third stage larvae after culture with edelfosine were not able to develop an infection in mice. Treatment of mice with edelfosine showed reduction of 47% in parasitic females allocated in the gut. Moreover, DNA fragmentation was observed by TUNEL staining in larvae treated with edelfosine. These results suggest that edelfosine could be an effective drug against strongyloidiasis, probably through induction of apoptosis-like cell death. PMID- 27394031 TI - Arrested development: coordinating regeneration with development and growth in Drosophila melanogaster. AB - The capacity for tissues to regenerate often varies during development. A better understanding how developmental context regulates regenerative capacity will be an important step towards enhancing the regenerative capacity of tissues to repair disease or damage. Recent work examining the regeneration of imaginal discs in the fruit fly, Drosophila melanogaster, has begun to identify mechanisms by which developmental progress restricts regeneration, and elucidate how Drosophila coordinates regenerative repair with the growth and development of the entire organism. Here we review recent advances in describing the interplay between development and tissue regeneration in Drosophila and identify questions that arise from these findings. PMID- 27394033 TI - Optical Coherence Tomography Angiography: A Useful Tool for Diagnosis of Treatment-Naive Quiescent Choroidal Neovascularization. AB - PURPOSE: To describe the optical coherence tomography angiography (OCT-A) features of treatment-naive quiescent choroidal neovascularization (CNV) secondary to age-related macular degeneration, and to estimate the detection rate for neovascularization by means of OCT-A. DESIGN: Diagnostic tool validity assessment. METHODS: Treatment-naive quiescent CNV were identified from a pool of patients at 2 retina referral centers. Patients underwent a complete ophthalmologic examination including fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and OCT-A. Detection rates of CNV by means of OCT-A were estimated with a second cohort of patients without CNV (negative controls). RESULTS: Twenty-two eyes of 20 consecutive patients with quiescent CNV were included. In 4 out of 22 eyes it was not possible to classify the CNV "shape," "core," "margin," and "location," either because the vascular network was not clearly shown (3 cases) or because it was not visible at all (1 case). CNV shape on OCT-A was rated as circular in 8 eyes and irregular in 10 eyes. CNV core was visible in 2 eyes. CNV margin was considered as well defined in 15 eyes and poorly defined in 3 eyes. CNV margin showed small loops in 9 eyes and large loops in the other 6 eyes. CNV location was foveal-sparing in 12 eyes. Sensitivity and specificity of quiescent CNV detection by OCT-A turned out to be 81.8% and 100%, respectively. CONCLUSIONS: OCT-A allows the clinician to noninvasively identify treatment-naive quiescent CNV and may be considered as a useful tool to guide the frequency of return visits and, possibly, make treatment decisions. PMID- 27394032 TI - Related factors to semi-recumbent position compliance and pressure ulcers in patients with invasive mechanical ventilation: An observational study (CAPCRI study). AB - BACKGROUND: Semi-recumbent position is recommended to prevent ventilator associated pneumonia. Its implementation, however, is below optimal. OBJECTIVES: We aimed to assess real semi-recumbent position compliance and the degree of head of-bed elevation in Spanish intensive care units, along with factors determining compliance and head-of-bed elevation and their relationship with the development of pressure ulcers. Finally, we investigated the impact that might have the diagnosis of pressure ulcers in the attitude toward head-of-bed elevation. METHODS: We performed a prospective, multicenter, observational study in 6 intensive care units. Inclusion criteria were patients >=18 years old and expected to remain under mechanical ventilator for >=48h. Exclusion criteria were patients with contraindications for semi-recumbent position from admission, mechanical ventilation during the previous 7 days and prehospital intubation. Head-of-bed elevation was measured 3 times/day for a maximum of 28 days using the BOSCH GLM80((r)) device. The variables collected related to patient admission, risk of pressure ulcers and the measurements themselves. Bivariate and multivariate analyses were carried out using multiple binary logistic regression and linear regression as appropriate. Statistical significance was set at p<0.05. All analyses were performed with IBM SPSS for Windows Version 20.0. RESULTS: 276 patients were included (6894 measurements). 45.9% of the measurements were <30.0 degrees . The mean head-of-bed elevation was 30.1 (SD 6.7) degrees and mean patient compliance was 53.6 (SD 26.1)%. The main reasons for non-compliance according to the staff nurses were those related to the patient's care followed by clinical reasons. The factors independently related to semi-recumbent position compliance were intensive care unit, ventilation mode, nurse belonging to the research team, intracranial pressure catheter, beds with head-of-bed elevation device, type of pathology, lateral position, renal replacement therapy, nursing shift, open abdomen, abdominal vacuum therapy and agitation. Twenty-five patients (9.1%) developed a total of 34 pressure ulcers. The diagnosis of pressure ulcers did not affect the head-of-bed elevation. In the multivariate analysis, head-of bed elevation was not identified as an independent risk factor for pressure ulcers. CONCLUSIONS: Semi-recumbent position compliance is below optimal despite the fact that it seems achievable most of the time. Factors that affect semi recumbent position include the particular intensive care unit, abdominal conditions, renal replacement therapy, agitation and bed type. Head-of-bed elevation was not related to the risk of pressure ulcers. Efforts should be made to clarify semi-recumbent position contraindications and further analysis of its safety profile should be carried out. PMID- 27394034 TI - Increased Choroidal Vascularity in Central Serous Chorioretinopathy Quantified Using Swept-Source Optical Coherence Tomography. AB - PURPOSE: To investigate the choroidal vascular structural changes in eyes with central serous chorioretinopathy (CSC) by using swept-source optical coherence tomography (SS-OCT). DESIGN: Prospective cross-sectional study. METHODS: We prospectively examined 40 eyes of 34 consecutive patients with CSC. Three dimensional choroidal images of the macular area, covering 3 * 3 mm and 6 * 6 mm, were obtained with SS-OCT. En face images of the microvasculature of the inner choroid and large choroidal vessel layers were converted to binary images. Choroidal vascular areas were analyzed quantitatively using the binary images. RESULTS: The choroidal vascular area was larger in eyes with CSC (the microvasculature of the inner choroid: 53.4% +/- 2.4%, P = .028; 3 * 3-mm large choroidal vessels: 66.9% +/- 7.1%, P < .001; and 6 * 6-mm large choroidal vessels: 64.8% +/- 7.3%, P < .001) than in age-matched normal eyes (52.2% +/- 1.8%, 54.9% +/- 4.4%, and 53.8% +/- 4.3%, respectively). The choroidal vascular area at the microvasculature of the inner choroid level was larger in multifocal posterior pigment epitheliopathy (55.8% +/- 2.2%) than in classic CSC (53.1% +/- 2.1%, P = .038) and in diffuse retinal pigment epitheliopathy (52.9% +/- 2.6%, P = .042). The subfoveal choroidal thickness was significantly associated with the choroidal vascular area at the level of large choroidal vessels (P < .001). CONCLUSIONS: Increased choroidal vascular area was observed in the whole macula area in eyes with CSC. This finding suggests that CSC may originate from a choroidal circulatory disturbance. PMID- 27394035 TI - Does the Shoe Fit? Ethical, Legal, and Policy Considerations of Global Positioning System Shoes for Individuals with Alzheimer's Disease. AB - As the overall incidence of Alzheimer's disease rises, the burden on caregivers and law enforcement institutions will increase to find individuals who wander. As such, technological innovations that could reduce this burden will become increasingly important. One such innovation is the GPS Shoe. As with any innovation involving the transfer of personal data to third parties, potential pitfalls with respect to loss of privacy and inadequate consent counterbalance the substantial promise of GPS shoes. To some extent, advance planning can mitigate these concerns, wherein individuals willingly elect to be monitored before their impairments progress to a stage that makes such authorization impractical. Nonetheless, tension may arise between the peace of mind of caregivers and family members and other important considerations at the intersection of autonomy, privacy, dignity, and consent. Ultimately, confronting ethical, legal, and policy considerations at the front end of product development and deployment will help ensure that new technologies are used wisely and that their lifesaving potential is realized. PMID- 27394037 TI - Corrigendum to "Nuclear factor-kappaB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog" [Arch. Biochem. Biophys. 598 (2016) 57-65]. PMID- 27394036 TI - Factors associated with the latency to diagnosis of childhood cancer in Peru. AB - BACKGROUND: The latency to diagnosis is the time between the detection of a patient's first symptoms and the cancer diagnosis. The aim of this study was to identify the latency to the diagnosis of cancer in children in Peru and the clinical and sociodemographic factors associated with this latency. METHODS: All patients diagnosed with lymphoma and solid tumors between 2012 and 2014 at a social security referral hospital in Peru were retrospectively evaluated. Clinical and demographic variables were analyzed to assess their association with the latency to diagnosis. RESULTS: A total of 284 patients younger than 18 years of age were included in the study. The median time to diagnosis was 8.8 weeks, with a median patient interval of 2 weeks and diagnostic interval of 4.4 weeks. We found significant differences in the latency to diagnosis for different types of cancer (longer for Hodgkin lymphoma and shorter for Wilms tumor). Older children had significantly longer latencies to diagnosis (P = 0.048; OR: 1.05, 95% CI [1.0-1.1]), as did children who were first diagnosed by a general physician rather than by a pediatrician or surgeon (P = 0.028; OR: 2.1, 95% CI [1.1-4.2]). Parental age, level of education, marital status, metastatic disease, clinical stage, and gender did not significantly affect latency to diagnosis as analyzed by a multivariate analysis. CONCLUSION: In Peru, median latency to diagnosis was comparable to that described in developing countries, where the index of suspicion for childhood cancer remains low. It is crucial to establish strategies to optimize early diagnoses using associated factors. PMID- 27394038 TI - Synthesis of three different galactose-based methacrylate monomers for the production of sugar-based polymers. AB - Glycopolymers, synthetic sugar-containing macromolecules, are attracting ever increasing interest from the chemistry community. Glycidyl methacrylate (GMA) is an important building block for the synthesis of sugar based methacrylate monomers and polymers. Normally, glycidyl methacrylate shows some advantages such as reactivity against nucleophiles or milder synthetic conditions such as other reactive methacrylate monomers. However, condensation reactions of glycidyl methacrylate with for instance protected galactose monomer leads to a mixture of two products due to a strong competition between the two possible pathways: epoxide ring opening or transesterification. In this paper, we propose two alternative routes to synthesize regiospecific galactose-based methacrylate monomers using the epoxy-ring opening reaction. In the first alternative route, the protected galactose is first oxidized to the acid in order to make it more reactive against the epoxide of GMA. In the second route, the protected sugar was first treated with epichlorohydrin followed by the epoxy ring opening reaction with methacrylic acid, to create an identical analogue of the ring-opening product of GMA. These two monomers were polymerized using conventional radical polymerization and were compared to the previously known galactose-methacrylate one. The new polymers show similar thermal stability but lower glass transition temperature (Tg) with respect to the known galactose methacrylate polymer. PMID- 27394039 TI - Application of amylomaltase for the synthesis of salicin-alpha-glucosides as efficient anticoagulant and anti-inflammatory agents. AB - The focus of this study was the synthesis of alpha-glucosyl derivatives of salicin by a transglucosylation reaction. The reaction was catalyzed by recombinant amylomaltase using tapioca starch as a glucosyl donor. Several reaction parameters, such as the enzyme-substrate concentrations, pH, temperature and incubation time, were optimized. Using the optimum conditions, at least three products with retention times (Rt) of 6.2, 9.2 and 14.1 were observed. The maximum yield of glucosylated salicin derivatives was 63% (w/w) of the total products. The structures of the glucosylated salicin derivatives were confirmed to be salicin-alpha-D-glucopyranoside, salicin-alpha-D-maltopyranoside and salicin-alpha-D-maltotriopyranoside through a combination of enzyme treatments, mass spectrometry and NMR analyses. The glycosidic bond between glucose units consisted of an alpha-1,4-configuration. The water solubility of salicin-alpha-D glucopyranoside, salicin-alpha-D-maltopyranoside and salicin-alpha-D maltotriopyranoside was 3-, 5- and 8-fold higher, respectively, than that of salicin, whereas their relative sweetness values were lower than that of sucrose. Interestingly, the long-chain salicin-alpha-D-glucosides showed greater anticoagulant and anti-inflammatory activities than salicin. In addition, the synthesized salicin-alpha-D-glucosides were able to tolerate acidic and high temperature conditions, but not alpha-glucosidase or human digestive enzymes. Therefore, these salicin-alpha-D-glucosides should be applied by the injection route to achieve greater bioavailability than is possible by the oral route. PMID- 27394040 TI - Real-time and long-time in vivo imaging in the shortwave infrared window of perforator vessels for more precise evaluation of flap perfusion. AB - Effective real-time and long-time in vivo imaging for flap perfusion requires bright and stable imaging agents whose emissions can effectively penetrate live tissues without photobleaching. Compared to the standard imaging agent today - intraoperative indocyanine green (ICG), quantum dots (QDs) is a more attractive alternative due to its excellent optical properties including broad emission spectrum and stability against photobleaching. Recent studies have confirmed that the shortwave infrared window (SWIR) between 1000 and 2300 nm is the most sensitive spectral range for in vivo imaging due to its extremely low tissue absorption and autofluorescence. Here, we, for the first time, report a novel approach of flap perfusion assessment that provides real-time and long-time in vivo imaging using lead sulfide (PbS) QDs. Our results show that PbS QDs, as an imaging agent, can improve the stability of in vivo high-resolution images in a sustained manner, thus facilitating the precise evaluation of flap perfusion. In summary, compared to current imaging reporters, SWIR QDs have high photostability and deep tissue penetration, which makes them as promising in vivo imaging agents for more precise evaluation of flap perfusion. PMID- 27394041 TI - Promoting the sexual and reproductive health of adolescent females in Ijebu-Ode, southwest, Nigeria: a study of sexual risk-taking. AB - Sexual risk-taking among adolescents, leads to several negative sexual and reproductive health outcomes such as unwanted pregnancies and sexually transmitted infections (STIs). This study assessed sexual risk behaviours and associated factors among in-school adolescent females in Ijebu-Ode, Nigeria. A cross-sectional study was carried out among 131 female adolescents selected via multi-stage sampling from senior secondary schools in Ijebu-Ode, southwest Nigeria. Data was collected using a validated, semi-structured, self-administered questionnaire and analysed using SPSS 17.0. Relevant descriptive and inferential statistics were calculated, with p set at <0.05. Participation was fully voluntary. The mean age of respondents was 16+/-1.3 years. Thirty-eight (14.5%) of respondents were sexually exposed with the mean age of sexual debut being 13.4+/-2.8 years. Participants with sexual exposure reported vaginal sex (89.5%), digital sex (36.8%) and oral sex (5.3%). A total of 42.1% had multiple sexual partners, 47.4% used condoms during sex. Only 13% of the respondents were engaged in sexual risk-taking. Factors associated with sexual risk-taking include: age, type of school, father being alive, having a boyfriend, age of boyfriend, low self-esteem and a history of non-consensual sex. Sexually-active adolescents engaged in risky sexual behaviours. Comprehensive sexuality education, behaviour change communication and adolescent-friendly services will adequately address the situation. PMID- 27394042 TI - Effectiveness of a modified dialectical behaviour therapy for adolescents within a stepped-care model. AB - OBJECTIVE: Early intervention with evidence-based treatment is important to halt the progression from early manifestations of personality disorder traits to adult personality disorders. The purpose of this study is to evaluate dialectical behaviour therapy (DBT) modified for an adolescent population with borderline personality disorder (BPD), offered within a stepped-care model. METHODS: Seven adolescents (M=1, F=6, Mage=16.86) diagnosed with either BPD or BPD traits participated in a modified 15-week DBT group. The group was offered within a stepped-care model, which required participants to have previously completed an 8 week distress-tolerance module. Pre/post scores on self-report measures of BPD symptomatology, including impulse control, emotional regulation and awareness, anxiety, depression, and substance use, were collected. RESULTS: Participants showed a post-treatment decrease in anxiety symptoms (large effect size) and disruptive behaviours (medium effect size). There was also an increase in emotional symptoms (medium effect size) and hyperactivity/inattention (medium effect size). CONCLUSION: The modified DBT group shows promise in alleviating symptoms of anxiety and some of the disruptive behaviours associated with BPD. The increase in emotional symptoms may be due to the expressive nature of DBT, and may contribute to their eventual therapeutic processing in the next step of the program. PMID- 27394043 TI - Obesity and facial dysmorphism in an adolescent patient with a 16p11.2 microdeletion. AB - A 17-year-old mixed race male has been followed in our adolescent clinic for severe obesity, dysmorphic features, and behavioral issues. Among other interventions, he has received symptomatic treatment for hypertension, insulin resistance, and attention deficit hyperactivity disorder. Genetic investigation identified a 16p11.2 microdeletion, commonly associated with severe obesity and developmental delay. We present the clinical history, treatment, and implications for this patient. PMID- 27394044 TI - Association between apolipoprotein E polymorphisms and premature coronary artery disease: a meta-analysis. AB - BACKGROUND: Although several studies have explored the genetic polymorphisms of apolipoprotein E (APOE) and their impact on premature coronary artery disease (PCAD), there is still some controversy regarding the significance of their association. Our aim is to estimate the association between APOE polymorphisms and PCAD via meta-analysis. METHODS: All relevant case-control studies and cohort studies published in Chinese or English prior to March 2016 were searched for in electronic databases. Detailed information concerning each piece of literature was independently extracted by two researchers. We used STATA11.0 to process all data and to determine the pooled odds ratio (OR). Altogether, four genetic models were applied to calculate OR and 95% confidence interval (CI): (1) epsilon2 allele vs. epsilon3 allele; (2) epsilon2 carriers vs. epsilon3/3; (3) epsilon4 allele vs. epsilon3 allele; (4) epsilon4 carriers vs. epsilon3/3. RESULTS: Eighteen studies concerning APOE polymorphisms and their impact on PCAD were included in the final analysis. The pooled analysis displayed that the epsilon2 allele and epsilon2 carriers increased the risk of PCAD significantly among Asians (OR 1.54; 95% CI, 1.09-2.17; OR 1.65; 1.10-2.47), while they showed protective effects on PCAD in Caucasians (OR 0.77; 95% CI, 0.62-0.95; OR 0.69; 0.54-0.89). Subjects with the epsilon4 allele and epsilon4 carriers showed significant associations with PCAD (OR 1.62; 95% CI, 1.27-2.06; OR 1.65; 1.27 2.15). CONCLUSIONS: Our investigation supported the fact that the epsilon2 allele in APOE may appear as a risk factor for PCAD in Asians while a protective factor in Caucasians and that the epsilon4 allele acted as a genetic risk factor for PCAD. PMID- 27394045 TI - Reply to: Comparing the visco-elastomeric fibrin polymerization assays FIBTEM(r) (ROTEM) vs. Functional Fibrinogen(r) (TEG): or why is a higher threshold for fibrinogen substitution better than a lower one? By Schochl et al. PMID- 27394046 TI - Cardiac troponins and mortality in type 1 and 2 myocardial infarction. AB - BACKGROUND: The pathogenesis of different types of myocardial infarction (MI) differs widely, so that accurate and timely differential diagnosis is essential for tailoring treatments according to the underlying causal mechanisms. As the measurement of cardiac troponins is a mainstay for diagnosis and management of MI, we performed a systematic literature analysis of published works which concomitantly measured cardiac troponins in type 1 and 2 MI. METHODS: The electronic search was conducted in Medline, Scopus and Web of Science using the keywords "myocardial infarction" AND "type(-)2" OR "type II" AND "troponin" in "Title/Abstract/Keywords", with no language restriction and date limited from 2007 to the present. RESULTS: Overall, 103 documents were identified, but 95 were excluded as precise comparison of troponin values in patients with type 1 and 2 MI was unavailable. Therefore, eight studies were finally selected for our analysis. Two studies used high-sensitivity (HS) immunoassays for measuring cardiac troponin T (HS-TnT), one used a HS immunoassay for measuring cardiac troponin I (HS-TnI), whereas the remaining used conventional methods for measuring TnI. In all studies, regardless of type and assay sensitivity, troponin values were higher in type 1 than in type 2 MI. The weighted percentage difference between type 1 and 2 MI was 32% for TnT and 91% for TnI, respectively. Post-discharge mortality obtained from pooling individual data was instead three times higher in type 2 than in type 1 MI. CONCLUSIONS: The results of our analysis suggest that the value of cardiac troponins is consistently higher in type 1 than in type 2 MI. PMID- 27394047 TI - An integrated proteomic and peptidomic assessment of the normal human urinome. AB - BACKGROUND: Urine represents an ideal source of clinically relevant biomarkers as it contains a large number of proteins and low molecular weight peptides. The comprehensive characterization of the normal urinary proteome and peptidome can serve as a reference for future biomarker discovery. Proteomic and peptidomic analysis of urine can also provide insight into normal physiology and disease pathology, especially for urogenital diseases. METHODS: We developed an integrated proteomic and peptidomic analytical protocol in normal urine. We employed ultrafiltration to separate protein and peptide fractions, which were analyzed separately using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on the Q-Exactive mass spectrometer. RESULTS: By analyzing six urines from healthy individuals with advanced age, we identified 1754 proteins by proteomic analysis and 4543 endogenous peptides, arising from 566 proteins by peptidomic analysis. Overall, we identified 2091 non-redundant proteins by this integrated approach. In silico protease activity analysis indicated that metalloproteases are predominantly involved in the generation of the endogenous peptide signature. In addition, a number of proteins that were detected in normal urine have previously been implicated in various urological malignancies, including bladder cancer and renal cell carcinoma (RCC). CONCLUSIONS: We utilized a highly sensitive proteomics approach that enabled us to identify one of the largest sets of protein identifications documented in normal human urine. The raw proteomics and peptidomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD003595. PMID- 27394048 TI - A simple colorimetric assay for measuring fructosamine 3 kinase activity. AB - BACKGROUND: Fructosamine 3 kinase (FN3K) is a deglycating enzyme, which may play a key role in reducing diabetes-induced organ damage by removing bound glucose from glycated proteins. We wanted to develop a simple colorimetric method for assaying FN3K activity in human body fluids. METHODS: Glycated bovine serum albumin (BSA) was obtained by glycation with a 10% glucose solution at 37 degrees C. After 72 h, glycated BSA was dialyzed against phosphate buffered saline (0.1 mol/L, pH 7.4). The dialyzed solution (containing +/-1000 umol/L fructosamine) was used as an FN3K substrate. In the assay, 300 uL of substrate was incubated with 50 uL of serum and 100 uL of MgCl2 (0.7 mmol/L)/ATP (3.2 mmol/L). The fructosamine concentration was determined at the start and after incubation (120 min, 25 degrees C). The decrease in fructosamine concentration over time is a measure for the FN3K activity (1 U corresponding to 1 umol/min). Concomitantly, the FN3K SNP rs1056534 and the ferroportin SNP rs1156350 were genotyped. RESULTS: Within-assay CV was 6.0%. Reference values for FN3K activity in serum were 14.2+/-1.6 U/L (n=143). Reference values for FN3K were neither age- nor sex-dependent. The various FN3K SNP rs1056534 genotypes showed no significant differences in serum FN3K activity. In diabetics (n=191), values (14.0+/-2.2 U/L) were comparable to those of the controls. FN3K activity in erythrocytes was significantly higher (170.3+/-7.6 U/L). The intra-erythrocytic FN3K activity makes the results prone to hemolysis. FN3K activity depended on the ferroportin Q248H genotypes, with the highest value for the wild type genotype. Neither transferrin saturation nor ferritin were confounders for the FN3K activity. FN3K activity was significantly (p<0.0001) correlated with HbA1c values, although the correlation between FN3K and HbA1c was weak. CONCLUSIONS: The simple colorimetric method allows determining FN3K activity in human serum. The assay may be useful for studying the impact of deglycation processes in diabetes mellitus. PMID- 27394049 TI - Detection of the common South-East Asian beta0-thalassemia mutations in samples with borderline HbA2 levels. PMID- 27394050 TI - New horizon in the treatment of sepsis: a systematic review of alternative medicine. AB - BackgroundDespite great advancement in treatment of sepsis, mortality of sepsis remains unacceptably high, even with the modern antibiotic and intensive care technologies. Considering the key role of immune dysfunction in sepsis pathophysiology, different treatments were evaluated, but failed to improve survival of patients. Natural remedies have been tested in various studies to overcome sepsis. In this study, we aim to review some of the evidence from clinical, in vitro and in vivo studies about the effect of alternative medicine on sepsis management. MethodsThe following databases were searched up to March 2014: PubMed, Scopus, Web of Science, Ovid and Google Scholar using combination of Mesh term. All in vitro and in vivo studies, also clinical trials, published in English, which evaluated alternative medicine in management of sepsis were included. Results Out of 95 relevant studies, the inclusion criteria were met for 79 cases. Among them, 18 studies were performed on humans. The most herbal medicine, including Xubijing (n=10) and then Rhubarb (n=3). Most of the reviewed botanical medicines modulate the immune system. Reduction of mortality was also reported in studies. ConclusionsModulation of immune system, anti-inflammatory activities and improvement of survival were the action of herbal medicine. A monovalent approach is not enough for treatment of sepsis, we recommend further studies to identify active component of herbal and use them in combination. Also an animal model of sepsis does not exactly mimic human sepsis, so more clinical studies should be performed. With no new drug on the horizon, herbal medicine will be promising for treatment of sepsis. PMID- 27394051 TI - In My Shoes - Validation of a computer assisted approach for interviewing children. AB - Interviewing young children presents a challenge because they tend to provide incomplete accounts and are easily misled. Therefore there is a need for techniques to improve young children's recall, while maintaining accuracy and increasing completeness. The computer-assisted interview In My Shoes (IMS) is an aid that potentially offers a way for young children to provide accounts of their experiences. This study examined the validity of IMS, by comparing it with a forensic best practice interview approach using a real-life clinical situation to ensure high ecological validity. Children were randomly assigned to either method and both accuracy and completeness of statements made by 4- and 5-year-olds (N=54) regarding a video-documented health check-up were assessed. The In My Shoes interviews were as good as best practice interviews on all accuracy measures for both age groups, except for object accuracy that was better in the forensic interview condition. Events description completeness was similar in both interview conditions; however, IMS interviews generated more complete statements about people present at the visit. The findings suggest that the IMS approach yields comparable results to a best practice interview, and it can be used as an alternative aid in child interviews. PMID- 27394052 TI - Maladaptive interpersonal schemas as sensitive and specific markers of borderline personality disorder among psychiatric inpatients. AB - Diagnostic criteria for borderline personality disorder (BPD) and mood and psychotic disorders characterized by major mood episodes (i.e., major depressive, bipolar and schizoaffective disorder) share marked overlap in symptom presentation, complicating differential diagnosis. The current study tests the hypothesis that maladaptive interpersonal schemas (MIS) are characteristic of BPD, but not of the major mood disorders. One hundred psychiatric inpatients were assessed by SCID I, SCID II and the Young Schema Questionnaire (YSQ-S2). Logistic regression analyses tested the association between MIS (measured by the YSQ-S2) and BPD, bipolar, major depressive and schizoaffective disorder. Receiver operator characteristic (ROC) curve analyses assessed the sensitivity and specificity of MIS as a marker of BPD. After covariation for comorbidity with each of the 3 mood disorders, BPD was robustly associated with 4 out of 5 schema domains. In contrast, only one of fifteen regression analyses demonstrated a significant association between any mood disorder and schema domain after covariation for comorbid BPD. ROC analyses of the 5 schema domains suggested Disconnection/Rejection had the greatest power for identification of BPD cases. These data support the specific role of maladaptive interpersonal schemas in BPD and potentially contribute to greater conceptual clarity about the distinction between BPD and the major mood disorders. PMID- 27394053 TI - The effectiveness of person-centred planning for people with intellectual disabilities: A systematic review. AB - OBJECTIVES: To evaluate the effectiveness of Person-Centred Planning (PCP) on outcomes for individuals with intellectual disabilities (ID) across the age range. METHOD: The electronic databases PsycInfo, Embase, CINHAL, PubMed, Web of Science, Scopus and Medline were searched for studies evaluating the impact of PCP on people with ID, published between 1990 and 2014; these were supplemented by manual searches of reference lists. Studies were considered irrespective of methodology, sample size and publication source, if outcomes reflected the impact of PCP on individuals with ID. RESULTS: Seven quantitative, five qualitative and four mixed methods studies were included in the review. The overall quality of the evidence was low but suggestive that PCP may have a positive, yet moderate, impact on some outcomes for individuals with ID, particularly community participation, participation in activities and daily choice-making. For other outcomes such as employment the findings were inconsistent. CONCLUSION: The evidence supporting the effectiveness of PCP is limited and does not demonstrate that PCP can achieve radical transformations in the lives of people with ID. Clearer descriptions of PCP and its components are needed. Small-scale successful demonstrations of effectiveness exist, but its clinical, cost-effectiveness and wider implementation must be investigated in large scale studies. PMID- 27394054 TI - Reply: Is Extended Sedation Necessary for Young Children Receiving High-Dose (131) I-MIBG Therapy? PMID- 27394055 TI - Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide in children and adolescents with hematological malignancies. AB - BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using posttransplant cyclophosphamide (Cy) for graft versus host disease (GVHD) prophylaxis has emerged as an alternative transplant strategy for patients without related donors, especially in the setting of limited resources in which T cell ex vivo depletion is not affordable. Experience with this transplant modality in children and adolescents is limited. PROCEDURE: We report a retrospective analysis of 25 consecutive outpatients under 21 years of age with high-risk hematological malignancies, who received a haplo-HSCT using posttransplant Cy as GVHD prophylaxis. RESULTS: Twenty-three (92%) of the 25 patients engrafted, and 20 (95%) of 21 evaluable subjects achieved full donor chimerism by day +30. One-year estimated overall survival and event-free survival were 50% and 33%, respectively. The cumulative incidence rate of severe acute GVHD was 19%, and 15% of patients developed chronic GVHD. CONCLUSIONS: Haplo-HSCT with posttransplant Cy is a feasible therapeutic option for children and adolescents with high-risk hematological malignancies in a limited resource setting. PMID- 27394056 TI - Understanding sleep problems in children with epilepsy: Associations with quality of life, Attention-Deficit Hyperactivity Disorder and maternal emotional symptoms. AB - PURPOSE: This study aimed to (1) compare sleep problems between children and adolescents with epilepsy and non-epileptic controls, and (2) examine whether there is an association between sleep problems and quality of life, Attention Deficit Hyperactivity Disorder (ADHD) and mothers' emotional symptoms. METHOD: Fifty-three patients from a cohort of epilepsy (aged 7-18 years) and 28 controls with minor medical problems (aged 7-18 years) were included. Parents completed Children's Sleep Habits Questionnaire (CSHQ) and Kinder Lebensqualitatsfragebogen: Children's Quality of Life Questionnaire-revised (KINDL-R) for patients and controls. Turgay DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S) parent and teacher forms were used to assess ADHD symptoms for patients. Mothers of the patients completed Beck Depression Inventory and State-Trait Anxiety Inventory (STAI). Neurology clinic charts were reviewed for the epilepsy-related variables. RESULTS: Children with epilepsy had a higher CSHQ Total score than the control group. Those with a CSHQ score >56 (which indicates moderate to severe sleep problems) had lower scores on KINDL-R. Parent-rated T-DSM-IV-S Total and Hyperactivity-Impulsivity scores, STAI trait and Beck scores were found to be higher in those with a CSHQ score >56. Significant positive correlations were found between CSHQ Total score and T-DSM IV-S, STAI trait and Beck scores. Binary logistic regression analysis revealed that T-DSM-IV-S Total, Inattention and Hyperactivity-Impulsivity scores were significantly associated with a higher CSHQ Total score. None of the epilepsy related variables were found to be related with the CSHQ Total score. CONCLUSION: Among children with epilepsy, sleep problems lead to a poor quality of life. The link between sleep problems and psychiatric symptoms must be conceptualized as a bilateral relationship. ADHD appears to be the strongest predictor of sleep problems. PMID- 27394057 TI - Psychogenic non-epileptic seizures (PNES) on the Internet: Online representation of the disorder and frequency of search terms. AB - PURPOSE: The nature of the symptoms associated with PNES require a multidisciplinary health team. There are too few professionals with an adequate understanding of PNES and therefore many are not able to provide patients with necessary information. In the age of the internet, it is not surprising that patients or caregivers might look for answers online. The purpose of this project was to investigate the online representation of PNES and search frequency for PNES and its associated terms. METHODS: To determine online representation, searches of: Google(r), twitter(r), YouTube(r), and Instagram(r) for "PNES" and associated terms were conducted. Websites, tweets, and films were classified by host and exclusivity of information. PNES and associated terms search frequency was determined through Google Trends(r). RESULTS: Professional and patient sites exclusively about PNES were outnumbered by sites that only mentioned PNES in fewer than three posts. Patients tended to favor less traditional hosting options than did professionals. On twitter(r), different keyword preferences were identified for professionals and patients. On YouTube(r) there was a substantial selection of videos of which 22 were professionally produced. Google Trends(r), revealed the terms most commonly used to search for this topic were in order: (1) "PNES;" (2) "NEAD;" and (3) "pseudoseizure." CONCLUSION: A variety of professional and patient internet content about PNES can be found online. Professional sites offered accurate and empirically-validated information on the disorder and tended to use traditional hosting options. Future professional initiatives might consider novel hosting options and higher-frequency terms to reach their audience more effectively. PMID- 27394058 TI - Understanding splenectomy for children with hereditary spherocytosis. PMID- 27394059 TI - Periodontal diseases and carotid intima-media thickness in Bangladesh. AB - AIM: To evaluate the relationship between periodontal diseases and subclinical atherosclerosis in a younger and lean South Asian population. METHODS: We conducted a cross-sectional study in 917 subjects (mean age 46 years and mean body mass index 21.1 kg/m2 ) from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Multivariate linear regression models were used to assess the associations between multiple clinical measures of periodontal diseases and carotid intima-media thickness (IMT). RESULTS: Mean attachment loss (AL) and percentage of sites with AL >= 4 mm (% AL >= 4) were associated with increased IMT. The IMT was 20.0-MUm (95% CI: 2.2, 37.8) and 26.5-MUm (95% CI: 8.9, 44.1) higher in subjects in the top quartile of mean AL (>3.72 mm) and % AL >= 4 (>58.4%), respectively, compared to those in the bottom quartile. In a subset of 366 subjects, mean AL was positively associated with plasma levels of matrix metalloproteinase-9 (p < 0.05) and soluble intercellular adhesion molecule-1 (p < 0.01). CONCLUSIONS: Attachment loss was associated with subclinical atherosclerosis in this young and lean Bangladeshi population. Future prospective studies are needed to confirm this association. PMID- 27394061 TI - Demetalation of copper undecaarylcorroles: Molecular structures of a free-base undecaarylisocorrole and a gold undecaarylcorrole. PMID- 27394060 TI - Influence of timing, radiation, and reconstruction on complications and speech outcomes with tracheoesophageal puncture. AB - BACKGROUND: We evaluated the impact of radiation, reconstruction, and timing of tracheoesophageal puncture (TEP) on complications and speech outcomes. METHODS: Retrospective review identified 145 patients who underwent TEP between 2003 and 2007. RESULTS: Ninety-nine patients (68%) had primary and 46 (32%) had secondary TEP, with complications occurring in 65% and 61%, respectively (p = .96). Twenty nine patients (20%) had major complications (18 primary and 11 secondary; p = .42). Ninety-four patients (65%) had pre-TEP radiation, 39 (27%) post-TEP radiation, and 12 (8%) no radiation. With patients grouped by TEP timing and radiation history, there was no difference in complications, fluency, or TEP use. With mean 4.7-year follow-up, 82% primary and 85% secondary used TEP for primary communication (p = .66). Free-flap patients used TEP more commonly for primary communication after secondary versus primary TEP (90% vs 50%; p = .02). CONCLUSION: Primary and secondary tracheoesophageal speakers experience similar high rates of complications. Extent of pharyngeal reconstruction, rather than radiation, may be more important in selection of TEP timing. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1765-1771, 2016. PMID- 27394062 TI - High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma. AB - AIM: To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma. MATERIALS AND METHODS: The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas. The diameters of the tumour and cavity, the maximum thickness of the cavity wall, shape of the cavity wall, the number of cavities, and the presence of ground-glass opacity, bronchial obstruction, intratumoural bronchiectasis, emphysema, and honeycombing were evaluated. The mechanisms of cavity formation were examined according to the pathological features. RESULTS: The maximum thickness of the cavity wall was significantly greater in squamous cell carcinomas than in adenocarcinomas (p=0.002). Ground-glass opacity and intratumoural bronchiectasis were significantly more common in adenocarcinomas than in squamous cell carcinomas (p<0.001 and p=0.040, respectively). Regarding the pathological findings, intratumoural bronchiectasis with or without alveolar wall destruction contributed to a significant difference between adenocarcinoma and squamous cell carcinoma (p<0.001; odds ratio [OR], 20.35; 95% confidence interval [CI], 3.87-107.10). CONCLUSION: The cavity wall tends to be thicker in squamous cell carcinomas than in adenocarcinomas. The presence of ground-glass opacity and intratumoural bronchiectasis is strongly suggestive of adenocarcinoma. PMID- 27394063 TI - Mutation spectra of RAS gene family in colorectal cancer. AB - BACKGROUND: The clinicopathologic features and frequency of KRAS mutations in colorectal cancer (CRC) patients have been reported; however, the characteristics and impact of NRAS and HRAS mutations on the survival of CRC patients have seldom been addressed. METHODS: Under institutional review board approval, 1,519 CRC patients who underwent surgery were enrolled. Mutation status of RAS was determined by polymerase chain reaction and mass spectrophotometry. RESULTS: The frequency of KRAS, NRAS, and HRAS mutations was 39.6%, 4.3%, and 1.7%, respectively. The KRAS mutation was associated with fewer left-sided tumors, fewer poor differentiated tumors, more mucin component, and less lymphovascular invasion. The NRAS or HRAS mutations were not associated with any of the clinicopathologic features examined. After univariate analysis, only NRAS mutation was associated with patients' overall and disease-free survival. However, the association of NRAS with patients' overall and disease-free survival disappeared after stepwise elimination. CONCLUSIONS: This study demonstrates the clinicopathologic characteristics of CRC patients with RAS mutations. Patients with NRAS mutation tended to have worse outcomes. PMID- 27394064 TI - Predictive value of preoperative serum C-reactive protein for recurrence after definitive surgical repair of enterocutaneous fistula. AB - BACKGROUND: Recurrence rates after surgical repair of enterocutaneous fistula (ECF) have not changed substantially. Serum C-reactive protein (s-CRP) has been used as an indicator of postoperative complications in abdominal surgery. The aim of this study was to determine the predictive value of preoperative s-CRP for recurrence after definitive surgical repair of ECF. METHODS: Fifty consecutive patients with ECF persistence submitted electively to definitive surgical repair (ECF resection with primary anastomosis) were included. Among several variables, preoperative s-CRP (primary independent variable) was assessed as a factor related to recurrence (dependent variable). Univariate and multivariate analyses were performed. RESULTS: ECF recurred in 19 patients (38%). Univariate and multivariate analyses disclosed operative blood loss greater than 325 mL (P < .05) and preoperative s-CRP greater than .5 mg/dL (P < .01) as the only risk factors for recurrence. ECF recurrence rates were significantly higher for patients with preoperative s-CRP above this level (53% vs 11%, P < .01). After conservative and surgical management, overall ECF closure was attained in 40 patients (80%). CONCLUSIONS: Our results suggest that s-CRP may serve as a useful parameter to predict potential failure (recurrence) in patients submitted to definitive closure of ECF. PMID- 27394065 TI - Author Reply. PMID- 27394066 TI - Editorial Comment. PMID- 27394067 TI - Scale-up of magnesium sulfate for treatment of pre-eclampsia and eclampsia in Nigeria. PMID- 27394068 TI - Local genetic structure and worldwide phylogenetic position of symbiotic Rhizobium leguminosarum strains associated with a traditional cultivated crop, Vicia ervilia, from Northern Morocco. AB - A total of 212 symbiotic bacteria were isolated from nodules of Vicia ervilia, a traditional crop cultivated in Northern Morocco. The isolates were recovered from 10 different sites, trapped each time with the local cultivar grown in the same field. Four loci were sequenced in order to characterize the isolates, including two housekeeping genes (recA and glnII), one plasmidic symbiotic gene (nodC) and one locus from another plasmid (prL11). In several isolates, two different copies of glnII were detected and sequenced, suggesting a unique duplication event, which has never been reported previously. There was no correlation between the genetic differentiation among cultivars and among bacteria, showing that the evolution of the bacterial population was independent, at least partially, from the host plant. By placing the haplotypes in a wide-ranging phylogenetic reconstruction, it was shown that the diversity detected in Morocco was spread throughout the different clades detected worldwide. The differentiation between areas relied on frequency variations of haplotypes rather than a presence/absence pattern. This finding raises new questions concerning bacterial genetic resource preservation, and confirms the old tenet "everything is everywhere but the environment selects". PMID- 27394069 TI - Bradyrhizobium centrosemae (symbiovar centrosemae) sp. nov., Bradyrhizobium americanum (symbiovar phaseolarum) sp. nov. and a new symbiovar (tropici) of Bradyrhizobium viridifuturi establish symbiosis with Centrosema species native to America. AB - In this work we analyze through a polyphasic approach several Bradyrhizobium strains isolated in Venezuela from root nodules of Centrosema species. The analysis of the 16S rRNA gene showed that the strains belong to three clusters within genus Bradyrhizobium which have 100% similarity with Bradyrhizobium daqingense CCBAU 15774(T)Bradyrhizobium guangxiense CCBAU 53363(T) and Bradyrhizobium viridifuturi SEMIA 690(T). The results of recA and glnII gene analysis confirmed the identification of the strains CMVU02 and CMVU30 as Bradyrhizobium viridifuturi but the nodC gene analysis showed that they belong to a new symbiovar for which we propose the name tropici. Nevertheless, the concatenated recA and glnII gene phylogenetic analysis, DNA-DNA hybridization and phenotypic characterization showed that the strains A9(T), CMVU44(T) and CMVU04 belong to two novel Bradyrhizobium species. The analysis of the nodC gene showed that these strains also represent two new symbiovars. Based on these results we propose the classification of the strain A9(T) isolated from Centrosema molle into the novel species Bradyrhizobium centrosemae (sv. centrosemae) sp. nov. (type strain A9(T)=LMG 29515(T)=CECT 9095(T)). and the classification of the strains CMVU44(T) and CMVU04 isolated from C. macrocarpum into the novel species Bradyrhizobium americanum (sv. phaseolarum) sp. nov. (type strain CMVU44(T)=LMG 29514(T)=CECT 9096(T)). PMID- 27394071 TI - Increased understanding leads to increased complexity: Molecular mechanisms of pulmonary arterial hypertension. PMID- 27394070 TI - Contingency Management Interventions for HIV, Tuberculosis, and Hepatitis Control Among Individuals With Substance Use Disorders: A Systematized Review. AB - Hepatitis, HIV and tuberculosis are significant and costly public health problems that disproportionately affect individuals with substance use disorders (SUDs). Incentive-based treatment approaches (i.e., contingency management; CM) are highly effective at reducing drug use. The primary aim of this report is to review the extant literature that examines the efficacy of CM interventions for the prevention, diagnosis and treatment of hepatitis, HIV and tuberculosis among individuals with SUDs. A literature search identified 23 controlled studies on this topic. In approximately 85% of the studies, CM produced significantly better adherence to prevention, diagnosis and treatment-related medical services, with adherence rates averaging almost 35% higher among patients receiving incentives vs. control condition participants. Findings from these studies parallel the results of a meta-analysis of CM interventions for the treatment of SUDs. The results also suggest that the principles that underlie the efficacy of CM generalize across infectious disease and substance abuse treatment behaviors. The application of additional principles from the literature on CM for treatment of SUDs to interventions targeting infectious disease control would be beneficial. Further development and dissemination of these interventions has the potential to greatly impact public health. PMID- 27394072 TI - Histological study on the protective role of vitamin B complex on the cerebellum of diabetic rat. AB - BACKGROUND: Disorder in cerebellar structure was reported in diabetes mellitus. B vitamins are involved in many significant metabolic processes within the brain. AIM OF THE WORK: To detect the protective role of vitamin B complex on the histological structure of the cerebellum of experimentally induced diabetic rat. MATERIAL & METHODS: Eighteen adult male Wistar rats were divided into two groups. Group I: normal vehicle control (n=6). Group II: streptozotocin-induced diabetic rats (n=12), which was equally divided into two subgroups; IIA (diabetic vehicle control), IIB (diabetic vitamin B complex-treated): streptozotocin-induced diabetic rats treated with vitamin B complex (1mg/kg/day) for 6 weeks. Specimens from the cerebellum were processed for light and electron microscopy. RESULTS: In vitamin B complex treated group, the histological changes in Purkinje cells, astrocytes and oligodendrocytes were improved compared with the diabetic non treated group. The white matter revealed intact myelinated axons. Inducible nitric oxide synthase (iNOS) and caspase-3 expression reduced. Glial fibrillary acidic protein (GFAP) expression revealed less activated astroglia. The number of Purkinje cells/mm(2) significantly increased. While, the number of GFAP positive astrocytes/mm(2) significantly decreased. In addition, the blood glucose level was reduced. CONCLUSION: Vitamin B complex protected the cerebellum from the histological changes which occurred in STZ- induced diabetic rats. PMID- 27394073 TI - Response to Letter to the Editor on "What Do Scottish Patients Expect of Their Total Knee Arthroplasty?". PMID- 27394074 TI - Preoperative Interventions and Charges Before Total Knee Arthroplasty. AB - BACKGROUND: The cost effectiveness of total knee arthroplasty (TKA) has been well established, but little data exist regarding preoperative interventions and their costs. The purpose of this study was to examine preoperative interventions and their associated charges within the 2-year period before TKA. METHODS: A retrospective cohort analysis of patients undergoing TKA between 2007 and 2011 was conducted using the PearlDiver Patient Record Database. Patients' inpatient and outpatient billing records were tracked over the 2-year period before receiving a TKA. RESULTS: A total of 35,596 patients from Medicare and 47,064 from United Healthcare underwent TKA from 2009 to 2011. In the 2-year period before TKA, the per patient average charge was $3545.82 for Medicare and $3281.57 for United Healthcare. In the 2-year period before TKA, 21.4% (Medicare) and 23.3% (United Healthcare) of all patients received a magnetic resonance imaging, with between 31.9% (Medicare) and 45.6% (United Healthcare) of these occurring within 3 months of surgery (P < .05). During this same period, 49.4% (Medicare) and 63.2% (United Healthcare) of all patients received an intra-articular injection, with between 29.4% (Medicare) and 44.8% (United Healthcare) of these occurring within 3 months of surgery (P < .05). CONCLUSION: Interventions and costs before TKA occur largely within 6 months preoperatively, with a substantial portion occurring within 3 months. These interventions may not be clinically or cost effective for certain patients, such as those with moderate-to-severe osteoarthritis. Foregoing these interventions and opting to perform TKA earlier may reduce costs and prevent unnecessary tests and procedures. PMID- 27394075 TI - Noise Exposure in TKA Surgery; Oscillating Tip Saw Systems vs Oscillating Blade Saw Systems. AB - BACKGROUND: Historically it has been suggested that noise-induced hearing loss (NIHL) affects approximately 50% of the orthopedic surgery personnel. This noise may be partially caused by the use of powered saw systems that are used to make the bone cuts. The first goal was to quantify and compare the noise emission of these different saw systems during total knee arthroplasty (TKA) surgery. A second goal was to estimate the occupational NIHL risk for the orthopedic surgery personnel in TKA surgery by quantifying the total daily noise emission spectrum during TKA surgery and to compare this to the Dutch Occupational Health Organization guidelines. METHODS: A conventional sagittal oscillating blade system with a full oscillating blade and 2 newer oscillating tip saw systems (handpiece and blade) were compared. Noise level measurements during TKA surgery were performed during cutting and hammering, additionally surgery noise profiles were made. RESULTS: The noise level was significantly lower for the oscillating tip saw systems compared to the conventional saw system, but all were in a range that can cause NIHL. The conventional system handpiece produced a considerable higher noise level compared to oscillating tip handpiece. CONCLUSION: NIHL is an underestimated problem in the orthopedic surgery. Solutions for decreasing the risk of hearing loss should be considered. The use of oscillating tip saw systems have a reduced noise emission in comparison with the conventional saw system. The use of these newer systems might be a first step in decreasing hearing loss among the orthopedic surgery personnel. PMID- 27394076 TI - The inverse link between genetic risk for schizophrenia and migraine through NMDA (N-methyl-D-aspartate) receptor activation via D-serine. AB - Schizophrenia has a considerable genetic background. Epidemiological studies suggest an inverse clinical association between schizophrenia and migraine. However, it is unclear to what extent this inverse comorbidity can be explained by genetic mechanisms or by schizophrenia-related behavioral factors. For both disorders hypotheses of glutamate N-methyl-D-aspartate (NMDA) receptor dysfunction have been developed in the past. We hypothesized that both conditions share common genetic factors with inverse effects, primary in the glutamatergic system and genes involved in NMDA activation. Data from the population based Study of Health in Pomerania (N=3973) were used. Based on the results from the recent genome-wide association study for schizophrenia, we calculated polygenic scores (PRS) for subsets of SNPs with different p-value cutoffs and for biological sub-entities. These scores were tested for an association of distinct biological pathways with migraine. The PRS for schizophrenia was inversely associated with migraine in our sample. This association was exclusively based on the genome-wide hits and on single nucleotide polymorphisms near or within genes encoding proteins involved in glutamatergic neurotransmission. This association could be attributed to a single intronic variant rs4523957 in SRR encoding serine racemase. Additional expression quantitative trait loci analyses of functional variants in SRR and gene-by-gene interaction analyses further supported the validity of this finding. SRR represents the rate limiting enzyme for the synthesis of D-serine, an important co-agonist of the NMDA receptor. According to our results, a decreased versus increased activation of NMDA receptors may play a role in the etiology of schizophrenia, as well as in migraine. PMID- 27394077 TI - Pathways leading to interleukin-12 production and protective immunity in cutaneous leishmaniasis. AB - Leishmaniasis affects millions of people worldwide and continues to pose public health problem. There is extensive evidence supporting the critical role for IL 12 in initiating and maintaining protective immune response to Leishmania infection. Although gene deletion studies show that CD40-CD40L interaction is an important pathway for IL-12 production by antigen-presenting cells and subsequent development of protective immunity in cutaneous leishmaniasis, several studies have uncovered other pathways that could also lead to IL-12 production and immunity in the absence of intact CD40-CD40L signaling. Here, we review the literature on the role of IL-12 in the induction and maintenance of protective T cell-mediated immunity in cutaneous leishmaniasis and the different pathways leading to IL-12 production by antigen-presenting cells following Leishmania major infection. PMID- 27394078 TI - Mutational analysis of COQ2 in patients with MSA in Italy. AB - COQ2 mutations have been implicated in the etiology of multiple system atrophy (MSA) in Japan. However, several genetic screenings have not confirmed the role of its variants in the disease. We performed COQ2 sequence analysis in 87 probable MSA. A homozygous change p.A43G was found in an MSA-C patient. Cosegregation analysis and the evaluation of CoQ10 content in muscle and fibroblasts did not support the pathogenic role of this variant. PMID- 27394079 TI - Starchy liquid burns do not have worse outcomes in children relative to hot beverage scalds. AB - AIM: To characterise children presenting with hot beverage scalds versus scalds caused by starchy water. METHODS: Retrospective survey of prospectively collected database of all children presenting over a two-year period. RESULTS: There were 138 starch scalds and 262 hot beverage injuries. Children with hot beverage injuries were significantly younger (18.2 months; IQR 14.1, 27.8) than those suffering starch scald injuries (51.4 months; 18.7, 102.3; p<0.001). Perineal burns were more common in the starch group than the hot beverage scald group (10.9% vs. 2.4%, p<0.001). Chest/breast and abdominal burns were more common in the hot beverage group than the starch group (60.7% vs. 36.9%, p<0.001). Children under three years of age in both groups are significantly less likely to receive adequate first aid at the scene (p<0.001). There are no differences in the need for skin grafting or scar management when comparing hot beverage scalds and scalds caused by starchy liquids. CONCLUSIONS: Scald injuries caused by starchy liquids do not appear to cause a more severe injury than hot beverage scalds. There is a different pattern of injury from starchy liquids in older children. Children under three years old are less likely to receive appropriate first aid at the scene. PMID- 27394080 TI - Tissue distribution of organochlorine pesticides in largemouth bass (Micropterus salmoides) from laboratory exposure and a contaminated lake. AB - Tissue concentrations of persistent organochlorine pesticides in laboratory exposed largemouth bass (Micropterus salmoides) and in bass collected from Lake Apopka, FL were determined by both total mass and lipid normalized mass to better understand the bioaccumulation pathways of contaminants. In the laboratory study, male bass were orally administered a single dose of a mixture of two pesticides (p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and dieldrin) and then fed uncontaminated food for 28 days. Gastrointestinal tract, liver, brain, gonad, kidney, spleen, and muscle were collected for chemical analysis. Different profiles were observed by total contaminant mass in tissues compared to lipid normalized mass. On a lipid normalized basis, p,p'-DDE was highest in the gastrointestinal tract followed by the liver, gonad, spleen, muscle, kidney and then brain. Dieldrin, on the other hand, was highest in the gastrointestinal tract and spleen and then followed by the gonad, muscle, liver, kidney, and brain. Distribution of the chemicals among the organs differed by their log KOW values and generally followed the blood flow path after the gastrointestinal tract. The low contaminant levels found in kidney and brain suggest insufficient time for equilibration into these tissues, especially into the brain where the blood-brain barrier may be slow to traverse. In Lake Apopka fish, dichlorodiphenyltrichloroethanes (DDXs, sum of p,p'-DDE, p,p'-DDD, and p,p'-DDT), Drins (sum of aldrin, dieldrin, and endrin), and hexachlorocyclohexanes (HCHs) were found. For DDXs, the lipid normalized concentrations in each tissue were about the same, as predicted from theory. For Drins and HCHs, the lipid normalized concentrations were similar for kidney, spleen, brain, gonad and muscle, but much lower in the gastrointestinal tract and liver, probably because of metabolism occurring in those tissues. PMID- 27394081 TI - High diversity of microcystins in a Microcystis bloom from an Algerian lake. AB - Microcystins (MCs) are cyanobacterial heptapeptides, produced by several genera and species of cyanobacteria, which have been involved in poisoning of animals throughout the world and have also been implicated in human health problems. They are regarded as the most frequently occurring and widespread of the cyanotoxins, with more than 100 MC variants reported to date including the present study. The lake des Oiseaux is a shallow permanent freshwater lake located in north-eastern Algeria. It is an important natural reserve playing a major role for the migratory birds after the crossing of the Mediterranean Sea and from the Sahara desert. In recent years, possibly related to increased eutrophication of the lake, massive blooms of cyanobacteria identified as Microcystis spp. have been observed. A bloom sample collected in September 2013 was analyzed by the serine/threonine phosphatase PP2A inhibition assay and liquid chromatography-mass spectrometry to determine respectively, the total concentration of MCs and the different variants of these toxins present. The results revealed that the Microcystis spp. bloom sample contained microcystins of which 21 putatively congeners were detected. Among these, 12 known microcystins (MC-RR, MC-LR, MC-FR, MC-WR, MC-YR, MC-LA, MC-(H4)YR, MC-HilR, [Asp(3)]MC-RAba, and [Glu(OCH3)(6)]MC LR) and two new congeners ([Asp(3)]MC-HarAba and [Glu(OCH3)(6)]MC-FR) were characterized, considering their molecular mass and the fragment ions produced by collision-induced dissociation of the [M+H](+) ions. MC-RR was the major (43.4%) in the bloom sample. PMID- 27394082 TI - Influence of temperature on phenanthrene toxicity towards nitrifying bacteria in three soils with different properties. AB - This study focused on the combined effect of environmental conditions (temperature) and contamination (polycyclic aromatic hydrocarbons, PAHs) on the activity of soil microorganisms (nitrifying bacteria). Phenanthrene (Phe) at five contamination levels (0, 1, 10, 100 and 1000 mg kg(-1) dry mass of soil) was employed as a model PAH compound in laboratory experiments that were conducted at three temperatures (i.e., 20 degrees C (recommended by ISO 15685 method), 15 and 30 degrees C). Three soils with different properties were used in these studies, and the activity of the nitrifying bacteria was assessed based on nitrification potential (NP) determinations. For the statistical evaluation of the results, the ANCOVA (analysis of covariance) method for three independent variables (i.e., temperature, phenanthrene concentration, soil matrix (as a qualitative variable)) and their interactions was employed. The results indicated on the significant interaction of all studied factors. Temperature influenced the toxicity of Phe towards NP, and this effect was related to the Phe concentration as well as was varied for the different soils. A low content of soil organic matter (controlling bioavailability of phenanthrene to soil microorganisms) enhanced the combined effect of temperature and Phe toxicity, and a high biological activity of the soil (high NP values) increased the effect of high temperature on the Phe stimulatory influence. The results indicate that the temperature should not be neglected in tests evaluating PAH ecotoxicity, especially for reliable ecological risk assessment. PMID- 27394083 TI - Oxidative transformation of iron monosulfides and pyrite in estuarine sediments: Implications for trace metals mobilisation. AB - Iron monosulfides are the initial iron sulfide minerals that form under reducing conditions in organic-rich sediments. Frequently referred as monosulfidic black ooze (MBO), these sediments exists in a range of anoxic systems including estuaries, coastal wetlands and permeable reactive barriers. The objective of this study was to investigate the transformation of solid phase sulfur, iron fractions and trace metals mobilisation in organic-rich hypersulfidic sediments during dredging. Two sediments from geographically contrasting sites in the Peel Harvey Estuary were collected and subjected to oxidation through resuspension over 14 days. During oxidation, redox potential rapidly and continuously increased, although minimal change in pH was observed in both sediments. The majority of FeS was oxidised within 48 h. Although not as dynamic as FeS, unusually high rates of FeS2 oxidation were measured in both sediments at circumneutral pH, with between 39 and 58% of FeS2 oxidised over 14 days. The rapid oxidation of FeS2 may be attributed to the presence of nano-size FeS2 crystals (~550-860 nm) with a high surface area. Before resuspension, solid bound Fe(total) was most abundant as measured by HCl-extractable Fe(II), followed by organic bound Fe(total) and oxide bound Fe(total). There was a marked decrease in these three fractions in both sediments during resuspension, with an increase in Fe(III) fraction. No significant release of trace metals was observed during resuspension of sulfidic sediments. However, disturbance to these estuarine sediments increases Fe(III) formation and further deteriorates the environment through smothering biological surfaces, deteriorating food sources and the quality of benthic habitats. PMID- 27394084 TI - Magnetic semiconductor photocatalysts for the degradation of recalcitrant chemicals from flow back water. AB - In the present study treatability of persistent organic compounds from the flow back water after hydrauling fracturing was investigated. The combination of TiO2 photocatalyst and magnetic oxide nanoparticles enhance the separation and recoverable property of nanosized TiO2 photocatalyst. Fe3O4/TiO2 and Fe3O4@SiO2/TiO2 nanocomposites were prepared by heteroagglomeration. The photocatalysts' characteristics by X-ray diffractometry (XRD), scanning electron microscopy (SEM), diffuse reflectance spectroscopy (DRS) showed that sample with the mass ratio of Fe3O4 to TiO2 equal 1:4 and molar ratio of TEOS:Fe3O4 = 8:1 and NH4OH:TEOS = 16:1 obtained by deposition TiO2 P25 (Evonik) on magnetite core had about 124 m2 g-1 specific surface area and superparamagnetic properties. The prepared composites contained TiO2 and Fe3O4 crystal phases. The photocatalytic activity was estimated by measuring the decomposition rate of three model pollutants identified in the flow back water from one of the Baltic Shale Basin. Regarding flow back water treatment after shale gas exploration, the progress of photocatalytic degradation of organic compounds was measured by chemical oxygen demand (COD) concentration. The Fe3O4@SiO2/TiO2_P25 composite nanoparticles were recovered and re-used without significant reduction of efficiency. PMID- 27394085 TI - Influence of catheter insertion on the hemodynamic environment in coronary arteries. AB - Intravascular stenting is one of the most commonly used treatments to restore the vascular lumen and flow conditions, while perioperative complications such as thrombosis and restenosis are still nagging for patients. As the catheter with crimped stent and folded balloon is directly advanced through coronary artery during surgery, it is destined to cause interference as well as obstructive effect on blood flow. We wonder how the hemodynamic environment would be disturbed and weather these disturbances cause susceptible factors for those complications. Therefore, a realistic three-dimensional model of left coronary artery was reconstructed and blood flow patterns were numerically simulated at seven different stages in the catheter insertion process. The results revealed that the wall shear stress (WSS) and velocity in left anterior descending (LAD) were both significantly increased after catheter inserted into LAD. Besides, the WSS on the catheter, especially at the ending of the catheter, was also at high level. Compared with the condition before catheter inserted, the endothelial cells of LAD was exposed to high-WSS condition and the risk of platelet aggregation in blood flow was increased. These influences may make coronary arteries more vulnerable for perioperative complications. PMID- 27394087 TI - Salivary Gland. Photon beam and particle radiotherapy: Present and future. AB - Salivary gland cancers (SGCs) are rare diseases and their treatment depends upon histology, stage and site of origin. Radical surgery is the mainstay of treatment but radiotherapy (RT) plays a key role in both the postoperative and the inoperable setting, as well as in recurrent disease. In the absence of prospective randomized trials, a wide retrospective literature suggests postoperative RT (PORT) in patients with high risk pathological features. SGCs, and adenoid cystic carcinoma (ACC) in particular, are known to be radio-resistant tumors and should therefore respond well to particle beam therapy. Recently, excellent outcome has been reported with radical carbon ion RT (CIRT) in particular for ACC. Both modern photon- and hadron-based treatments are effective and are characterized by a favourable toxicity profile. But it is not clear whether one modality is superior to the other for disease control, due to the differences in patients' selection, techniques, fractionation schedules and outcome measurements among clinical experiences. In this paper, we review the role of photon and particle RT for malignant SGCs, discussing the difference between modalities in terms of biological and technical characteristics. RT dose and target volumes for different histologies (ACC versus non-ACC) have also been taken into consideration. PMID- 27394086 TI - Influence of biofilm formation on the optical properties of novel bioactive glass containing composites. AB - OBJECTIVE: Bioactive glass (BAG) has been suggested as a possible additive for dental restorative materials because of its antimicrobial effect and potential for promoting apatite formation in body fluids. The purpose of this study was to investigate the effects of bacterial biofilm on the change of colorimetric value and translucency of novel BAG-containing composites having different initial surface roughness. METHODS: Composites with 72wt% total filler load were prepared by replacing 15% of the silanized Sr glass with BAG (65 mol % Si; 4% P; 31% Ca), BAG-F (61% Si; 31% Ca; 4% P; 3% F; 1% B), or silanized silica. Light-cured discs of 2-mm thickness (n=10/group) were divided into 4 different surface roughness subgroups produced by wet polishing with 600 and then up to 1200, 2400, or 4000 grit SiC. CIE L*a*b* were measured and the color difference and translucency parameter (TP) were calculated before and after incubating in media with or without a Streptococcus mutans (UA 159) biofilm for 2 wks (no agitation). Results were analyzed using ANOVA/Tukey's test (alpha=0.05). RESULTS: All the color differences for BAG and BAG-F composite showed significant decreases with bacterial biofilm compared to media-only. The mean TP (SD) of BAG and BAG-F composite before aging [10.0 (2.8) and 8.5 (1.4)] was higher than that of the control composite [4.9 (0.8)], while the change in TP with aging was greater compared to the control with or without bacteria. BAG-F composites with the smoothest surfaces showed a greater decrease in TP under bacterial biofilm compared to the BAG composite. SIGNIFICANCE: Highly polished dental composites containing bioactive glass additives may become slightly rougher and show reduced translucency when exposed to bacterial biofilms, but do not discolor any more than control composites that do not contain the BAG. PMID- 27394088 TI - Successive pH- and heat-induced homogenous liquid-liquid extraction. AB - A simple and efficient analytical method known as pH- and heat-induced homogenous liquid-liquid extraction combined with high-performance liquid chromatography has been successfully developed for the extraction and determination of neonicotinoid pesticides in aqueous samples. In this method, a few mL of a water-miscible basic extraction solvent is mixed with a high volume of an aqueous phase containing the analytes and passed through a tube which a portion of the tube is filled with sodium carbonate as a separating agent. By passing the solution, salt is dissolved and the fine droplets of the extraction solvent are formed. The produced droplets go up through the remained solution and collect as a separated layer. In the following, the collected organic phase is removed and placed into a micro tube. Then it is heated in a water bath to form two phases. Several experimental parameters that influence extraction efficiency such as type and volume of extraction solvent, type of phase separation agent, temperature, and extraction time were investigated. Under the optimum conditions, the extraction recoveries and enrichment factors ranged between 51 and 81% and 680 and 1080, respectively. Calibration curves showed a high-level of linearity for all target analytes with coefficients of determination ranging between 0.997 and 0.999. The repeatability of the proposed method expressed as relative standard deviation varied between 3 and 5% (n=6, C=50MUgL(-1)), and the detection limits were in the range of 0.52-1.0MUgL(-1). Finally, the performance of the method was evaluated by analyzing the selected pesticides in different fruit juice and vegetable samples. PMID- 27394089 TI - Fabrication of a biomimetic adsorbent imprinted with a common specificity determinant for the removal of alpha- and beta-amanitin from plasma. AB - alpha-Amanitin and beta-amanitin are the main toxins of mushroom poisoning. The application of traditional non-selective adsorbents is not satisfactory in clinical treatment of amanita mushroom poisoning due to lack of specificity adsorption capability of these adsorbents toward amanitin toxins. In the current work, we introduce a novel molecularly imprinted biomimetic adsorbent based on a ligand specificity determinant through surface imprinted strategy. Owing to the expensive price of the amanitin sources, we selected a typical common moiety of alpha, beta-amanitin as specificity determinant to synthesize a template necessary for the preparation of molecularly imprinted polymers (MIPs). Computer simulation was used to initially select acidic methacrylic acid (MAA) and basic 4 vinyl pyridine (4-VP) together as functional monomers. The experiments further demonstrated that the synergistic interaction of MAA and 4-VP played a primary role in the recognition of alpha, beta-amanitin by MIPs. By means of batch and packed-bed column experiment and the hemocompatibility evaluation, the resultant biomimetic adsorbent has been proved to be capable of selectively removing alpha, beta-amanitin and possess good hemocompatibility. This novel adsorbent has great potential to find application in human plasma purification. PMID- 27394090 TI - High perceived social support protects against the intergenerational transmission of obesity: The Cardiovascular Risk in Young Finns Study. AB - AIMS: Our aims were to assess whether offspring social support moderates the relationship between parental body mass index (BMI) and offspring BMI. METHODS: A prospective design was used with an analytic sample of 1049 participants from Finland (the offspring) who were 35-50years old in 2012 when adulthood BMI was measured. Parental BMI was self-reported at baseline in 1980. Offspring social support was measured in 2007 when participants were 30-45years old. Linear and logistic regression was used to examine whether there was an interaction between parental BMI and offspring social support when predicting offspring BMI in adulthood. An analysis of simple slopes and multilevel growth curve modeling were used to further examine the interaction. RESULTS: The interaction between maternal BMI and offspring social support was significantly and negatively related to offspring BMI in adulthood (beta=-0.068, R(2) change=0.005, p=0.015) in the fully adjusted model which also adjusted for parental occupational status and offspring depressive symptoms. The logistic regression supported these results, with the interaction between maternal overweight (BMI>=25kg/m(2)) and offspring social support negatively associated with offspring overweight in adulthood (odds ratio=0.74, 95% confidence interval, 0.56 to 0.98). The growth curve analysis further demonstrated that high maternal BMI predicts more rapidly rising offspring BMI in those reporting low social support compared to high social support. CONCLUSIONS: Our results suggest that social support protects against the intergenerational transmission of obesity and therefore presents an important opportunity for obesity prevention efforts. PMID- 27394091 TI - Communication: XUV transient absorption spectroscopy of iodomethane and iodobenzene photodissociation. AB - Time-resolved extreme ultraviolet (XUV) transient absorption spectroscopy of iodomethane and iodobenzene photodissociation at the iodine pre-N4,5 edge is presented, using femtosecond UV pump pulses and XUV probe pulses from high harmonic generation. For both molecules the molecular core-to-valence absorption lines fade immediately, within the pump-probe time-resolution. Absorption lines converging to the atomic iodine product emerge promptly in CH3I but are time delayed in C6H5I. We attribute this delay to the initial pi -> sigma(*) excitation in iodobenzene, which is distant from the iodine reporter atom. We measure a continuous shift in energy of the emerging atomic absorption lines in CH3I, attributed to relaxation of the excited valence shell. An independent particle model is used to rationalize the observed experimental findings. PMID- 27394092 TI - Communication: Energy transfer and reaction dynamics for DCl scattering on Au(111): An ab initio molecular dynamics study. AB - Scattering and dissociative chemisorption of DCl on Au(111) are investigated using ab initio molecular dynamics with a slab model, in which the top two layers of Au are mobile. Substantial kinetic energy loss in the scattered DCl is found, but the amount of energy transfer is notably smaller than that observed in the experiment. On the other hand, the dissociative chemisorption probability reproduces the experimental trend with respect to the initial kinetic energy, but is about one order of magnitude larger than the reported initial sticking probability. While the theory-experiment agreement is significantly improved from the previous rigid surface model, the remaining discrepancies are still substantial, calling for further scrutiny in both theory and experiment. PMID- 27394093 TI - Extension of the basis set of linearized augmented plane wave (LAPW) method by using supplemented tight binding basis functions. AB - In order to increase the accuracy of the linearized augmented plane wave (LAPW) method, we present a new approach where the plane wave basis function is augmented by two different atomic radial components constructed at two different linearization energies corresponding to two different electron bands (or energy windows). We demonstrate that this case can be reduced to the standard treatment within the LAPW paradigm where the usual basis set is enriched by the basis functions of the tight binding type, which go to zero with zero derivative at the sphere boundary. We show that the task is closely related with the problem of extended core states which is currently solved by applying the LAPW method with local orbitals (LAPW+LO). In comparison with LAPW+LO, the number of supplemented basis functions in our approach is doubled, which opens up a new channel for the extension of the LAPW and LAPW+LO basis sets. The appearance of new supplemented basis functions absent in the LAPW+LO treatment is closely related with the existence of the ul-component in the canonical LAPW method. We discuss properties of additional tight binding basis functions and apply the extended basis set for computation of electron energy bands of lanthanum (face and body centered structures) and hexagonal close packed lattice of cadmium. We demonstrate that the new treatment gives lower total energies in comparison with both canonical LAPW and LAPW+LO, with the energy difference more pronounced for intermediate and poor LAPW basis sets. PMID- 27394094 TI - Matrix product operators, matrix product states, and ab initio density matrix renormalization group algorithms. AB - Current descriptions of the ab initio density matrix renormalization group (DMRG) algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational parallelism. The connections and correspondences described here serve to link the future developments with the past and are important in the efficient implementation of continuing advances in ab initio DMRG and related algorithms. PMID- 27394095 TI - Speeding up local correlation methods: System-inherent domains. AB - A new approach to determine local virtual space in correlated calculations is presented. It restricts the virtual space in a pair-specific manner on the basis of a preceding approximate calculation adapting automatically to the locality of the studied problem. The resulting pair system-inherent domains are considerably smaller than the starting domains, without significant loss in the accuracy. Utilization of such domains speeds up integral transformations and evaluations of the residual and reduces memory requirements. The system-inherent domains are especially suitable in cases which require high accuracy, e.g., in generation of pair-natural orbitals, or for which standard domains are problematic, e.g., excited-state calculations. PMID- 27394097 TI - Improved scaling of temperature-accelerated dynamics using localization. AB - While temperature-accelerated dynamics (TAD) is a powerful method for carrying out non-equilibrium simulations of systems over extended time scales, the computational cost of serial TAD increases approximately as N(3) where N is the number of atoms. In addition, although a parallel TAD method based on domain decomposition [Y. Shim et al., Phys. Rev. B 76, 205439 (2007)] has been shown to provide significantly improved scaling, the dynamics in such an approach is only approximate while the size of activated events is limited by the spatial decomposition size. Accordingly, it is of interest to develop methods to improve the scaling of serial TAD. As a first step in understanding the factors which determine the scaling behavior, we first present results for the overall scaling of serial TAD and its components, which were obtained from simulations of Ag/Ag(100) growth and Ag/Ag(100) annealing, and compare with theoretical predictions. We then discuss two methods based on localization which may be used to address two of the primary "bottlenecks" to the scaling of serial TAD with system size. By implementing both of these methods, we find that for intermediate system-sizes, the scaling is improved by almost a factor of N(1/2). Some additional possible methods to improve the scaling of TAD are also discussed. PMID- 27394096 TI - Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model. AB - Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules. PMID- 27394098 TI - First principles prediction of amorphous phases using evolutionary algorithms. AB - We discuss the efficacy of evolutionary method for the purpose of structural analysis of amorphous solids. At present, ab initio molecular dynamics (MD) based melt-quench technique is used and this deterministic approach has proven to be successful to study amorphous materials. We show that a stochastic approach motivated by Darwinian evolution can also be used to simulate amorphous structures. Applying this method, in conjunction with density functional theory based electronic, ionic and cell relaxation, we re-investigate two well known amorphous semiconductors, namely silicon and indium gallium zinc oxide. We find that characteristic structural parameters like average bond length and bond angle are within ~2% of those reported by ab initio MD calculations and experimental studies. PMID- 27394099 TI - Laplace-transformed atomic orbital-based Moller-Plesset perturbation theory for relativistic two-component Hamiltonians. AB - We present a formulation of Laplace-transformed atomic orbital-based second-order Moller-Plesset perturbation theory (MP2) energies for two-component Hamiltonians in the Kramers-restricted formalism. This low-order scaling technique can be used to enable correlated relativistic calculations for large molecular systems. We show that the working equations to compute the relativistic MP2 energy differ by merely a change of algebra (quaternion instead of real) from their non relativistic counterparts. With a proof-of-principle implementation we study the effect of the nuclear charge on the magnitude of half-transformed integrals and show that for light elements spin-free and spin-orbit MP2 energies are almost identical. Furthermore, we investigate the effect of separation of charge distributions on the Coulomb and exchange energy contributions, which show the same long-range decay with the inter-electronic/atomic distance as for non relativistic MP2. A linearly scaling implementation is possible if the proper distance behavior is introduced to the quaternion Schwarz-type estimates as for non-relativistic MP2. PMID- 27394100 TI - Maximum efficiency of state-space models of nanoscale energy conversion devices. AB - The performance of nano-scale energy conversion devices is studied in the framework of state-space models where a device is described by a graph comprising states and transitions between them represented by nodes and links, respectively. Particular segments of this network represent input (driving) and output processes whose properly chosen flux ratio provides the energy conversion efficiency. Simple cyclical graphs yield Carnot efficiency for the maximum conversion yield. We give general proof that opening a link that separate between the two driving segments always leads to reduced efficiency. We illustrate these general result with simple models of a thermoelectric nanodevice and an organic photovoltaic cell. In the latter an intersecting link of the above type corresponds to non-radiative carriers recombination and the reduced maximum efficiency is manifested as a smaller open-circuit voltage. PMID- 27394101 TI - Spin contamination-free N-electron wave functions in the excitation-based configuration interaction treatment. AB - This work deals with the spin contamination in N-electron wave functions provided by the excitation-based configuration interaction methods. We propose a procedure to ensure a suitable selection of excited N-electron Slater determinants with respect to a given reference determinant, required in these schemes. The procedure guarantees the construction of N-electron wave functions which are eigenfunctions of the spin-squared operator S^(2), avoiding any spin contamination. Our treatment is based on the evaluation of the excitation level of the determinants by means of the expectation value of an excitation operator formulated in terms of spin-free replacement operators. We report numerical determinations of energies and expectation values, arising from our proposal as well as from traditional configuration interaction methods, in selected open-shell systems, in order to compare the behavior of these procedures and their computational costs. PMID- 27394102 TI - Infrared spectroscopy of molecular ions in selected rotational and spin-orbit states. AB - First results are presented obtained with an experimental setup developed to record IR spectra of rotationally state-selected ions. The method we use is a state-selective version of a method developed by Schlemmer et al. [Int. J. Mass Spectrom. 185, 589 (1999); J. Chem. Phys. 117, 2068 (2002)] to record IR spectra of ions. Ions are produced in specific rotational levels using mass-analyzed threshold-ionization spectroscopy. The state-selected ions generated by pulsed field ionization of Rydberg states of high principal quantum number (n ~ 200) are extracted toward an octupole ion guide containing a neutral target gas. Prior to entering the octupole, the ions are excited by an IR laser. The target gas is chosen so that only excited ions react to form product ions. These product ions are detected mass selectively as a function of the IR laser wavenumber. To illustrate this method, we present IR spectra of C2H2 (+) in selected rotational levels of the (2)Piu,3/2 and (2)Piu,1/2 spin-orbit components of the vibronic ground state. PMID- 27394103 TI - Long-lived coherence in pentafluorobenzene as a probe of pipi(*) - pisigma(*) vibronic coupling. AB - The dynamics of pentafluorobenzene after femtosecond laser excitation to the optically bright pipi(*) first excited electronic state have been investigated by femtosecond time-resolved time-of-flight mass spectrometry and femtosecond time resolved photoelectron imaging spectroscopy. The observed temporal profiles exhibit a bi-exponential decay behavior with a superimposed, long-lived, large amplitude oscillation with a frequency of nuosc = 78-74 cm(-1) and a damping time of tauD = 5-2 ps. On the basis of electronic structure and quantum dynamics calculations, the oscillations have been shown to arise due to vibronic coupling between the optically bright pipi(*) state and the energetically close-lying optically dark pisigma(*) state. The coupling leads to a pronounced double-well character of the lowest excited adiabatic potential energy surface along several out-of-plane modes of b1 symmetry. The optical electronic excitation initiates periodic wavepacket motion along these modes. In the out-of-plane distorted molecular configuration, the excited state acquires substantial pisigma(*) character, thus modulating the ionization probability. The photoelectron spectra and the anisotropy of their angular distribution confirm the periodically changing electronic character. The ionizing probe laser pulse directly maps the coupled electron-nuclear motion into the observed signal oscillations. PMID- 27394104 TI - Full-dimensional global potential energy surfaces describing abstraction and exchange for the H + H2S reaction. AB - For the H + H2S system, ~34 000 data points are sampled over a large configuration space including both abstraction and exchange channels, and calculated at the level of explicitly correlated unrestricted coupled cluster method with singles, doubles, and perturbative triples excitations with the augmented correlation-consistent polarized triple zeta basis set (UCCSD(T) F12a/aug-cc-pVTZ). The data set was fit using the newly proposed permutation invariant polynomial-neural network (PIP-NN) method with three different vectors as the input: two redundant sets of PIPs, one with the maximum order four (PES-I) and one with the maximum order three (PES-II), and nine non-redundant PIPs (PES III). All these PESs show small fitting errors and essentially the same performance in representing the title system. Various kinetics and dynamical properties are calculated using the tunneling corrected transition state theory and quasi-classical trajectory, and compared with available experimental results. At a collision energy of 10 kcal/mol, both the H2 and SH products are found to be internally cold, with ~20% of H2 at its first vibrational excited state, while SH is essentially a spectator. The angular distributions of the products are mainly in backward with considerable contributions from sideway direction. In addition, analytical partial derivatives of any PIP-NN PES with respect to the coordinates of atoms are derived by making use of the monomial symmetrization algorithm [Z. Xie and J. M. Bowman, J. Chem. Theory Comput. 6, 26-34 (2010)]. It can not only accelerate the evaluation of the derivatives, but also improve the energy convergence significantly. PMID- 27394105 TI - Thermally and vibrationally induced conformational isomerizations, infrared spectra, and photochemistry of gallic acid in low-temperature matrices. AB - Near-infrared (near-IR) narrowband selective vibrational excitation and annealing of gallic acid (3,4,5-trihydroxybenzoic acid) isolated in cryogenic matrices were used to induce interconversions between its most stable conformers. The isomerizations were probed by infrared spectroscopy. An extensive set of quantum chemical calculations, carried out at the DFT(B3LYP)/6-311++G(d,p) level of approximation, was used to undertake a detailed analysis of the ground state potential energy surface of the molecule. This investigation of the molecule conformational space allowed extracting mechanistic insights into the observed annealing- or near-IR-induced isomerization processes. The infrared spectra of the two most stable conformers of gallic acid in N2, Xe, and Ar matrices were fully assigned. Finally, the UV-induced photochemistry of the matrix isolated compound was investigated. PMID- 27394106 TI - The thermal decomposition of the benzyl radical in a heated micro-reactor. II. Pyrolysis of the tropyl radical. AB - Cycloheptatrienyl (tropyl) radical, C7H7, was cleanly produced in the gas-phase, entrained in He or Ne carrier gas, and subjected to a set of flash-pyrolysis micro-reactors. The pyrolysis products resulting from C7H7 were detected and identified by vacuum ultraviolet photoionization mass spectrometry. Complementary product identification was provided by infrared absorption spectroscopy. Pyrolysis pressures in the micro-reactor were roughly 200 Torr and residence times were approximately 100 MUs. Thermal cracking of tropyl radical begins at 1100 K and the products from pyrolysis of C7H7 are only acetylene and cyclopentadienyl radicals. Tropyl radicals do not isomerize to benzyl radicals at reactor temperatures up to 1600 K. Heating samples of either cycloheptatriene or norbornadiene never produced tropyl (C7H7) radicals but rather only benzyl (C6H5CH2). The thermal decomposition of benzyl radicals has been reconsidered without participation of tropyl radicals. There are at least three distinct pathways for pyrolysis of benzyl radical: the Benson fragmentation, the methyl phenyl radical, and the bridgehead norbornadienyl radical. These three pathways account for the majority of the products detected following pyrolysis of all of the isotopomers: C6H5CH2, C6H5CD2, C6D5CH2, and C6H5 (13)CH2. Analysis of the temperature dependence for the pyrolysis of the isotopic species (C6H5CD2, C6D5CH2, and C6H5 (13)CH2) suggests the Benson fragmentation and the norbornadienyl pathways open at reactor temperatures of 1300 K while the methyl phenyl radical channel becomes active at slightly higher temperatures (1500 K). PMID- 27394107 TI - Infrared absorption of t-HOCO(+), H(+)(CO2)2, and HCO2 (-) produced in electron bombardment of CO2 in solid para-H2. AB - We have employed electron bombardment during matrix deposition of CO2 (or (13)CO2, C(18)O2) and para-hydrogen (p-H2) at 3.2 K and recorded infrared (IR) spectra of t-HOCO(+), H(+)(CO2)2, HCO2 (-), CO2 (-), t-HOCO, and other species isolated in solid p-H2. After the matrix was maintained in darkness for 13 h, intensities of absorption features of t-HOCO(+) at 2403.5 (nu1), 2369.9 (nu2), 1018.1 (nu4), and 606.5 (nu6) cm(-1) and those of H(+)(CO2)2 at 1341.1, 883.6, and 591.5 cm(-1) decreased. Corresponding lines of isotopologues were observed when (13)CO2 or C(18)O2 replaced CO2. In contrast, lines of HCO2 (-) at 2522.4 (nu1), 1616.1 (nu5), 1327.9 (nu2), and 745.6 (nu3) cm(-1) increased in intensity; corresponding lines of H(13)CO2 (-) or HC(18)O2 (-) were also observed. Lines of t-DOCO(+) and DCO2 (-) were observed in an electron bombarded CO2 /normal deuterium (n-D2) matrix. Data of nu6 of t-HOCO(+) and all observed modes of H(18)OC(18)O(+) and HC(18)O2 (-) are new. The assignments were made according to expected chemical behavior, observed isotopic shifts, and comparisons with vibrational wavenumbers and relative intensities of previous reports and calculations with the B3PW91/aug-cc-pVQZ method. The nu1 line of t-HOCO(+) in solid p-H2 (2403.5 cm(-1)), similar to the line at 2673 cm(-1) of t-HOCO(+) tagged with an Ar atom, is significantly red-shifted from that reported for gaseous t-HOCO(+) (3375.37 cm(-1)) due to partial proton sharing between CO2 and H2 or Ar. The nu1 line of HCO2 (-) in solid p-H2 (2522.4 cm(-1)) is blue shifted from that reported for HCO2 (-) in solid Ne (2455.7 cm(-1)) and that of HCO2 (-) tagged with Ar (2449 cm(-1)); this can be explained by the varied solvation effects by Ne, Ar, or H2 on the mixing of H(+) + CO2 and H + CO2 (-) surfaces. Possible formation mechanisms of t-HOCO(+), H(+)(CO2)2, HCO2 (-), CO2 (-), t HOCO, H2O, and t-HCOOH are discussed. PMID- 27394108 TI - Electric-field-driven electron-transfer in mixed-valence molecules. AB - Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate the electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted. PMID- 27394109 TI - Resolving the energy and temperature dependence of C6H6 (*) collisional relaxation via time-dependent bath temperature measurements. AB - The relaxation of highly vibrationally excited benzene, generated by 193 nm laser excitation, was studied using the transient rotational-translational temperature rise of the N2 bath, which was measured by proxy using two-line laser induced fluorescence of seeded NO. The resulting experimentally measured time-dependent N2 temperature rises were modeled with MultiWell based simulations of Collisional Energy Transfer (CET) from benzene vibration to N2 rotation-translation. We find that the average energy transferred in benzene deactivating collisions depends linearly on the internal energy of the excited benzene molecules and depends approximately linearly on the N2 bath temperature between 300 K and 600 K. The results are consistent with experimental studies and classical trajectory calculations of CET in similar systems. PMID- 27394110 TI - Thermal relaxation of molecular oxygen in collisions with nitrogen atoms. AB - Investigation of O2-N collisions is performed by means of the quasi-classical trajectory method on the two lowest ab initio potential energy surfaces at temperatures relevant to hypersonic flows. A complete set of bound-bound and bound-free transition rates is obtained for each precollisional rovibrational state. Special attention is paid to the vibrational and rotational relaxations of oxygen as a result of chemically non-reactive interaction with nitrogen atoms. The vibrational relaxation of oxygen partially occurs via the formation of an intermediate NO2 complex. The efficient energy randomization results in rapid vibrational relaxation at low temperatures, compared to other molecular systems with a purely repulsive potential. The vibrational relaxation time, computed by means of master equation studies, is nearly an order of magnitude lower than the relaxation time in N2-O collisions. The rotational nonequilibrium starts to play a significant effect at translational temperatures above 8000 K. The present work provides convenient relations for the vibrational and rotational relaxation times as well as for the quasi-steady dissociation rate coefficient and thus fills a gap in data due to a lack of experimental measurements for this system. PMID- 27394111 TI - Molecular dynamics simulation of a binary mixture near the lower critical point. AB - 2,6-lutidine molecules mix with water at high and low temperatures but in a wide intermediate temperature range a 2,6-lutidine/water mixture exhibits a miscibility gap. We constructed and validated an atomistic model for 2,6-lutidine and performed molecular dynamics simulations of 2,6-lutidine/water mixture at different temperatures. We determined the part of demixing curve with the lower critical point. The lower critical point extracted from our data is located close to the experimental one. The estimates for critical exponents obtained from our simulations are in a good agreement with the values corresponding to the 3D Ising universality class. PMID- 27394112 TI - Dynamic signature of molecular association in methanol. AB - Quasielastic neutron scattering measurements and molecular dynamics simulations were combined to investigate the collective dynamics of deuterated methanol, CD3OD. In the experimentally determined dynamic structure factor, a slow, non Fickian mode was observed in addition to the standard density-fluctuation heat mode. The simulation results indicate that the slow dynamical process originates from the hydrogen bonding of methanol molecules. The qualitative behavior of this mode is similar to the previously observed alpha-relaxation in supercooled water [M. C. Bellissent-Funel et al., Phys. Rev. Lett. 85, 3644 (2000)] which also originates from the formation and dissolution of hydrogen-bonded associates (supramolecular clusters). In methanol, however, this mode is distinguishable well above the freezing transition. This finding indicates that an emergent slow mode is not unique to supercooled water, but may instead be a general feature of hydrogen-bonding liquids and associating molecular liquids. PMID- 27394113 TI - Accurate Monte Carlo simulations on FCC and HCP Lennard-Jones solids at very low temperatures and high reduced densities up to 1.30. AB - Canonical Monte Carlo simulations on face-centered cubic (FCC) and hexagonal closed packed (HCP) Lennard-Jones (LJ) solids are conducted at very low temperatures (0.10 <= T(*) <= 1.20) and high densities (0.96 <= rho(*) <= 1.30). A simple and robust method is introduced to determine whether or not the cutoff distance used in the simulation is large enough to provide accurate thermodynamic properties, which enables us to distinguish the properties of FCC from that of HCP LJ solids with confidence, despite their close similarities. Free-energy expressions derived from the simulation results are also proposed, not only to describe the properties of those individual structures but also the FCC-liquid, FCC-vapor, and FCC-HCP solid phase equilibria. PMID- 27394114 TI - Dielectric constant of water in the interface. AB - We define the dielectric constant (susceptibility) that should enter the Maxwell boundary value problem when applied to microscopic dielectric interfaces polarized by external fields. The dielectric constant (susceptibility) of the interface is defined by exact linear-response equations involving correlations of statistically fluctuating interface polarization and the Coulomb interaction energy of external charges with the dielectric. The theory is applied to the interface between water and spherical solutes of altering size studied by molecular dynamics (MD) simulations. The effective dielectric constant of interfacial water is found to be significantly lower than its bulk value, and it also depends on the solute size. For TIP3P water used in MD simulations, the interface dielectric constant changes from 9 to 4 when the solute radius is increased from ~5 to 18 A. PMID- 27394115 TI - Geometric and energetic considerations of surface fluctuations during ion transfer across the water-immiscible organic liquid interface. AB - Molecular dynamics simulations and umbrella sampling free energy calculations are used to examine the thermodynamics, energetics, and structural fluctuations that accompany the transfer of a small hydrophilic ion (Cl(-)) across the water/nitrobenzene interface. By examining several constrained interface structures, we isolate the energetic costs of interfacial deformation and co transfer of hydration waters during the ion transfer. The process is monitored using both energy-based solvation coordinates and a geometric coordinate recently introduced by Morita and co-workers to describe surface fluctuations. Our simulations show that these coordinates provide a complimentary description of the water surface fluctuations during the transfer and are necessary for elucidating the mechanism of the ion transfer. PMID- 27394116 TI - Computational study of effect of water finger on ion transport through water-oil interface. AB - When an ion transports from water to oil through water-oil interface, it accompanies hydrated water molecules and transiently forms a chain of water, called "water finger." We thoroughly investigated the role of the water finger in chloride ion transport through water-dichloromethane interface by using molecular dynamics technique. We developed a proper coordinate w to describe the water finger structure and calculated the free energy landscape and the friction for the ion transport as a function of ion position z and the water finger coordinate w. It is clearly shown that the formation and break of water finger accompanies an activation barrier for the ion transport, which has been overlooked in the conventional free energy curve along the ion position z. The present analysis of the friction does not support the hypothesis of augmented local friction (reduced local diffusion coefficient) at the interface. These results mean that the experimentally observed rate constants of interfacial ion transfer are reduced from the diffusion-limited one because of the activation barrier associated to the water finger, not the anomalous local diffusion. We also found that the nascent ion just after the break of water finger has excessive hydration water than that in the oil phase. PMID- 27394117 TI - Ab initio study of vacancy formation in cubic LaMnO3 and SmCoO3 as cathode materials in solid oxide fuel cells. AB - Doped LaMnO3 and SmCoO3 are important solid oxide fuel cell cathode materials. The main difference between these two perovskites is that SmCoO3 has proven to be a more efficient cathode material than LaMnO3 at lower temperatures. In order to explain the difference in efficiency, we need to gain insight into the materials' properties at the atomic level. However, while LaMnO3 has been widely studied, ab initio studies on SmCoO3 are rare. Hence, in this paper, we perform a comparative DFT + U study of the structural, electronic, and magnetic properties of these two perovskites. To that end, we first determined a suitable Hubbard parameter for the Co d-electrons to obtain a proper description of SmCoO3 that fully agrees with the available experimental data. We next evaluated the impact of oxygen and cation vacancies on the geometry, electronic, and magnetic properties. Oxygen vacancies strongly alter the electronic and magnetic structures of SmCoO3, but barely affect LaMnO3. However, due to their high formation energy, their concentrations in the material are very low and need to be induced by doping. Studying the cation vacancy concentration showed that the formation of cation vacancies is less energetically favorable than oxygen vacancies and would thus not markedly influence the performance of the cathode. PMID- 27394118 TI - Adlayer structure dependent ultrafast desorption dynamics in carbon monoxide adsorbed on Pd (111). AB - We report our ultrafast photoinduced desorption investigation of the coverage dependence of substrate-adsorbate energy transfer in carbon monoxide adlayers on the (111) surface of palladium. As the CO coverage is increased, the adsorption site population shifts from all threefold hollows (up to 0.33 ML), to bridge and near bridge (>0.5 to 0.6 ML) and finally to mixed threefold hollow plus top site (at saturation at 0.75 ML). We show that between 0.24 and 0.75 ML this progression of binding site motifs is accompanied by two remarkable features in the ultrafast photoinduced desorption of the adsorbates: (i) the desorption probability increases roughly two orders magnitude, and (ii) the adsorbate substrate energy transfer rate observed in two-pulse correlation experiments varies nonmonotonically, having a minimum at intermediate coverages. Simulations using a phenomenological model to describe the adsorbate-substrate energy transfer in terms of frictional coupling indicate that these features are consistent with an adsorption-site dependent electron-mediated energy coupling strength, etael, that decreases with binding site in the order: three-fold hollow > bridge and near bridge > top site. This weakening of etael largely counterbalances the decrease in the desorption activation energy that accompanies this progression of adsorption site motifs, moderating what would otherwise be a rise of several orders of magnitude in the desorption probability. Within this framework, the observed energy transfer rate enhancement at saturation coverage is due to interadsorbate energy transfer from the copopulation of molecules bound in three-fold hollows to their top-site neighbors. PMID- 27394119 TI - A semi-analytical calculation of the electrostatic pair interaction between nonuniformly charged colloidal spheres at an air-water interface. AB - We study the electrostatic pair interaction between two nonuniformly like-charged colloidal spheres trapped in an air-water interface. Under the linear Poisson Boltzmann approximation, a general form of the electrostatic potential for the system is shown in terms of multipole expansions. After combining the translation rotation transform of the coordinates with the numerical multipoint collection, we give a semi-analytical result of the electrostatic pair interaction between the colloids. The pair interaction changes quantitatively or even qualitatively with different distributions of the surface charges on the particles. Because of the anisotropic distribution of the surface charge and the asymmetric dielectric medium, the dipole moment of the ion cloud associating with the particle orients diagonally to the air-water interface with an angle alpha. When the angle is large, the colloids interact repulsively, while they attract each other when the angle is small. The attractive colloids may be "Janus-like" charged and be arranged with some specific configurations. Whatever the repulsions or the attractions, they all decay asymptotically ?1/d(3) (d is the center-center distance of the particles) which is consistent with our general acknowledge. The calculation results also provide an insight of the effect of the ion concentration, particle size, and the total charge of the particle on the pair interaction between the particles. PMID- 27394121 TI - Stiffness parameter of brush-like polymers with rod-like side chains. AB - The stiffness parameter lambda(-1) of brush-like polymers having rod-like side chains with the hard core potential was calculated. Side chains are, first, assumed to be connected with a free joint to the main chain. The free energy per molecule F was calculated invoking the single contact approximation in which only the interaction between two side chains is considered and the higher interactions are ignored. In the calculation, the contact is assumed to occur when the two side chains are in a plain and the condition for the angles between the side chain and the main chain to make a triangle by two side chains and the main chain was exactly taken into account. The change of F after bending the main chain with a certain curvature from the straight state was calculated to obtain lambda(-1). The resulting lambda(-1) came close to the experimental value for brush-like polymers with a poly(methacrylate) main chain and poly(hexylisocyanate) (PHIC) side chains if we add a constant as the intrinsic stiffness of the main chain, lambda0 (-1), to it. By considering the potential function having a minimum when the angle between the side and main chains equals pi/2, the data for brush-like polymers with a poly(styrene) main chain and PHIC side chains were also closely fitted by the theoretical values with an appropriate value of lambda0 (-1) and the force constant of the angle. PMID- 27394120 TI - Electrostatics of polymer translocation events in electrolyte solutions. AB - We develop an analytical theory that accounts for the image and surface charge interactions between a charged dielectric membrane and a DNA molecule translocating through the membrane. Translocation events through neutral carbon based membranes are driven by a competition between the repulsive DNA-image charge interactions and the attractive coupling between the DNA segments on the trans and the cis sides of the membrane. The latter effect is induced by the reduction of the coupling by the dielectric membrane. In strong salt solutions where the repulsive image-charge effects dominate the attractive trans-cis coupling, the DNA molecule encounters a translocation barrier of ~10 kBT. In dilute electrolytes, the trans-cis coupling takes over image-charge forces and the membrane becomes a metastable attraction point that can trap translocating polymers over long time intervals. This mechanism can be used in translocation experiments in order to control DNA motion by tuning the salt concentration of the solution. PMID- 27394122 TI - Asymmetrical phase separation and gelation in binary mixtures of oppositely charged colloids. AB - Two types of colloidal particles, which are nearly the same in chemical composition but carry opposite surface charges, are mixed in water. Depending on the relative proportion of the oppositely charged particles, the process of aggregation leads to the formation of discrete clusters of various sizes in dilute dispersions, and to the development of particle gel networks in more concentrated systems. Due to the significant difference in the absolute values of surface charges (negative particle: -48 mV, positive particle: +24 mV), the phase separation and the gelation behaviors are asymmetric with respect to the mixing ratio. Mixtures with excess negative particles are more stable, while mixtures with excess positive particles are easily affected by phase separation. The hetero-aggregation triggered by the addition of microscopically large macro-ions is similar to what is often observed in a mono-component charged colloidal system, i.e., phase separation occurs through addition of small electrolyte ions. Within the concentration region investigated here, it is clear that the gel line is buried inside the phase separation region. Gelation occurs only when the number and size of the clusters are large and big enough to connect up into a space-spanning network. Our results indicate that, in this binary mixture of oppositely charged colloids, although the interaction between unlike species is attractive and that between like species is repulsive, the onset of gelation is in fact governed by the equilibrium phase separation, as in the case of purely attractive systems with short-range isotropic interaction. PMID- 27394123 TI - Hydrodynamic interaction between particles near elastic interfaces. AB - We present an analytical calculation of the hydrodynamic interaction between two spherical particles near an elastic interface such as a cell membrane. The theory predicts the frequency dependent self- and pair-mobilities accounting for the finite particle size up to the 5th order in the ratio between particle diameter and wall distance as well as between diameter and interparticle distance. We find that particle motion towards a membrane with pure bending resistance always leads to mutual repulsion similar as in the well-known case of a hard-wall. In the vicinity of a membrane with shearing resistance, however, we observe an attractive interaction in a certain parameter range which is in contrast to the behavior near a hard wall. This attraction might facilitate surface chemical reactions. Furthermore, we show that there exists a frequency range in which the pair-mobility for perpendicular motion exceeds its bulk value, leading to short lived superdiffusive behavior. Using the analytical particle mobilities we compute collective and relative diffusion coefficients. The appropriateness of the approximations in our analytical results is demonstrated by corresponding boundary integral simulations which are in excellent agreement with the theoretical predictions. PMID- 27394124 TI - Winding angles of long lattice walks. AB - We study the winding angles of random and self-avoiding walks (SAWs) on square and cubic lattices with number of steps N ranging up to 10(7). We show that the mean square winding angle of random walks converges to the theoretical form when N -> infinity. For self-avoiding walks on the square lattice, we show that the ratio /(2) converges slowly to the Gaussian value 3. For self-avoiding walks on the cubic lattice, we find that the ratio /(2) exhibits non-monotonic dependence on N and reaches a maximum of 3.73(1) for N ~ 10(4). We show that to a good approximation, the square winding angle of a self-avoiding walk on the cubic lattice can be obtained from the summation of the square change in the winding angles of lnN independent segments of the walk, where the ith segment contains 2(i) steps. We find that the square winding angle of the ith segment increases approximately as i(0.5), which leads to an increase of the total square winding angle proportional to (lnN)(1.5). PMID- 27394125 TI - Mode localization in the cooperative dynamics of protein recognition. AB - The biological function of proteins is encoded in their structure and expressed through the mediation of their dynamics. This paper presents a study on the correlation between local fluctuations, binding, and biological function for two sample proteins, starting from the Langevin Equation for Protein Dynamics (LE4PD). The LE4PD is a microscopic and residue-specific coarse-grained approach to protein dynamics, which starts from the static structural ensemble of a protein and predicts the dynamics analytically. It has been shown to be accurate in its prediction of NMR relaxation experiments and Debye-Waller factors. The LE4PD is solved in a set of diffusive modes which span a vast range of time scales of the protein dynamics, and provides a detailed picture of the mode dependent localization of the fluctuation as a function of the primary structure of the protein. To investigate the dynamics of protein complexes, the theory is implemented here to treat the coarse-grained dynamics of interacting macromolecules. As an example, calculations of the dynamics of monomeric and dimerized HIV protease and the free Insulin Growth Factor II Receptor (IGF2R) domain 11 and its IGF2R:IGF2 complex are presented. Either simulation-derived or experimentally measured NMR conformers are used as input structural ensembles to the theory. The picture that emerges suggests a dynamical heterogeneous protein where biologically active regions provide energetically comparable conformational states that are trapped by a reacting partner in agreement with the conformation selection mechanism of binding. PMID- 27394126 TI - Note: From reaction-diffusion systems to confined Brownian motion. PMID- 27394127 TI - Erratum: "Coupled-cluster based basis sets for valence correlation calculations" [J. Chem. Phys. 144, 104106 (2016)]. PMID- 27394128 TI - Erratum: "Communication: Near-locality of exchange and correlation density functionals for 1- and 2-electron systems" [J. Chem. Phys. 144, 191101 (2016)]. PMID- 27394129 TI - Prevalence and degree of bother of pelvic floor disorder symptoms among women from primary care and specialty clinics in Lebanon: an exploratory study. AB - INTRODUCTION AND HYPOTHESIS: The prevalence of pelvic floor disorders (PFD) and their impact on quality of life of women vary among different populations. The purpose of this study was to assess the prevalence of symptoms of PFD, and their degree of bother in a convenience sample of Lebanese women, and to evaluate health-care seeking (HCS) behavior related to PFD. METHODS: Women visiting clinics in a University Medical Center in Beirut, Lebanon, completed the self filled validated Arabic version of the Global Pelvic Floor Bother Questionnaire (PFBQ). Data covering demographics, comorbidities, and HCS behavior related to PFD were collected. Total individual PFBQ scores, individual PFD symptom scores and HCS behavior were correlated to demographic data and comorbidities. RESULTS: The study participants included 900 women. PFBQ scores were significantly higher in women of older age, women with a lower level of education, women with higher vaginal parity, and women who engaged in heavy lifting/physical activity. BMI >25 kg/m2 was the strongest independent risk factor for the presence of PFD symptoms. The overall prevalence of urinary incontinence was 42 %. Anal incontinence was the most bothersome PFD. Almost two thirds of the women reported HCS due to any aspect of PFD. Among symptomatic women who believed that their PFD warranted HCS, financial concern was the most common obstacle irrespective of age and educational level. CONCLUSIONS: In this convenience sample of Lebanese women, PFD symptoms were common and were significantly correlated with demographic characteristics and self-reported comorbidities. The key reason for not seeking health care related to PFD was financial concern. PMID- 27394130 TI - Synergistic effect of KIR ligands missing and cytomegalovirus reactivation in improving outcomes of haematopoietic stem cell transplantation from HLA-matched sibling donor for treatment of myeloid malignancies. AB - The goal of this study was to evaluate the influence of KIR-HLA genotypes on the outcome of patients undergoing treatment for haematological malignancies by non-T depleted lymphocyte haematopoietic stem cell transplantation (HSCT) from HLA matched sibling donors. The prospective study was conducted at the Center of Hematology, University of Campinas, and 50 patients and their donors were followed up from 2008 to 2014. KIR and HLA class I genes were genotyped and patients grouped based on the presence of KIR ligands combined with KIR genotype of their respective donors. Patients with all KIR ligands present (n=13) had a significantly higher (p=0.04) incidence of acute graft-versus-host-disease (GVHD) than patients with one or more KIR ligands missing (n=37). The overall survival following transplantation of patients with myeloid malignancies (n=27) was significantly higher (p=0.035) in the group with one or more KIR ligands missing (n=18) than in the group with all ligands present (n=9). Presence of KIR2DS2 was associated with a worsening of HSCT outcome while reactivation of cytomegalovirus (CMV) infection improved the outcome of patients with one or more KIR ligands missing. Our results indicate that KIR-HLA interactions affect the outcome of the HLA-matched transplantation, particularly in patients with myeloid malignancies. PMID- 27394131 TI - Expression of p40 (?Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role. AB - According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ?Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I. PMID- 27394132 TI - Comparison of two different modes of molecular adsorbent recycling systems for liver dialysis. AB - BACKGROUND: In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. CASE DIAGNOSIS/TREATMENT: We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient's cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. CONCLUSION: OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure. PMID- 27394133 TI - Micafungin-Induced Suicidal Erythrocyte Death. AB - BACKGROUND/AIMS: The antifungal drug Micafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. Side effects of Micafungin treatment include microangiopathic hemolytic anemia and thrombocytopenia with microvascular thrombosis. The development of thrombosis may be fostered by stimulation of eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, activated protein kinase C (PKC), casein kinase 1alpha or p38 kinase and activated caspases. The present study explored, whether Micafungin induces eryptosis. METHODS: Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Hemolysis was quantified by measuring haemoglobin concentration in the supernatant. RESULTS: A 48 hours exposure of human erythrocytes to Micafungin (10 - 25 ug/ml) significantly increased hemolysis and the percentage of annexin-V-binding cells, and significantly decreased forward scatter. Micafungin (25 ug/ml) did not significantly modify Fluo3-fluorescence, DCFDA fluorescence, or ceramide abundance. The effect of Micafungin on annexin-V-binding was not significantly modified by removal of extracellular Ca2+, by PKC inhibitor staurosporine (1 uM), p38 kinase inhibitor SB203580 (2 uM), casein kinase 1alpha inhibitor D4476 (10 uM) or pancaspase inhibitor zVAD (10 uM). CONCLUSIONS: Micafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane. PMID- 27394134 TI - Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. AB - The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n = 70), AET (n = 64), or RET (n = 66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32 kg/m(2); p = 0.017), UE-MD (0.12 kg/kg; p < 0.001), and LE-MD (0.27 kg/kg; p < 0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p = 0.039) and dynapenia (p = 0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95 % confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95 % CI -4.0 to 24.1]), and fatigue (5.3 points [95 % CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL. PMID- 27394135 TI - Mutational Spectrum of CYP24A1 Gene in a Cohort of Italian Patients with Idiopathic Infantile Hypercalcemia. AB - BACKGROUND/AIMS: Loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-24 hydroxylase, have been recognized as a cause of elevated 1,25 dihydroxyvitamin D concentrations, hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis in infants and adults. As only a case report describing 2 adult patients has been reported in Italian population, we report here the mutation analysis of CYP24A1 gene in an Italian cohort of 12 pediatric and adult patients with idiopathic infantile hypercalcemia (IIH). METHODS: We performed mutational screening of CYP24A1 gene in a cohort of 12 Italian patients: 8 children with nephrocalcinosis, hypercalcemia and PTH levels <10 pg/ml and 4 adult patients with nephrolithiasis, mild hypercalcemia and PTH levels <10 pg/ml from 11 unrelated Italian families. Clinical and biochemical data were collected. Genomic DNA was extracted from peripheral blood leucocytes using standard methods, and whole coding sequence of CYP24A1 gene was analysed in all patients and family members by polymerase chain reaction and direct sequencing. The potential pathogenicity of the newly identified missense mutations was evaluated by 3 different in silico approaches (Sorting Intolerant from Tolerant, Polyphen and Mutation Taster) and by comparative analysis in 14 different species using ClustalW software. RESULTS: CYP24A1 bi-allelic mutations were found in 8 individuals from 7 Italian families (7/11; 64%). Overall, 6 different CYP24A1 mutations, including one small deletion (p.Glu143del), 4 missense mutations (p.Leu148Pro; p.Arg396Trp; p.Pro503Leu; p.Glu383Gln) and one nonsense mutation (p.Tyr220*) were identified. Two out of 6 mutations (p.Tyr220* and p.Pro503Leu) were not previously described. Moreover, a new CYP24A1 variant was identified by genetic screening of asymptomatic controls. CONCLUSION: To the best of our knowledge, this is the first report of a CYP24A1 molecular analysis performed in an Italian cohort of adult and pediatric Italian patients. This study (1) confirms that CYP24A1 plays a causal role in some but not all cases of IIH (64%); (2) expands the spectrum of known CYP24A1 pathogenic mutations; (3) describes 2 hotspots detected in 50% of all Italian cases; and (4) emphasizes the importance of recognition and genetic diagnosis of CYP24A1 defects in infantile as well as adult hypercalcemia. PMID- 27394137 TI - Commentary on: Comparison of complication rates related to male urethral slings and artificial urinary sphincters for urinary incontinence: national multi institutional analysis of ACS-NSQIP database. PMID- 27394136 TI - Thermo-sensitive hydrogel for preventing bowel injury in percutaneous renal radiofrequency ablation. AB - PURPOSE: Percutaneous radiofrequency ablation (PRFA) has been used to ablate renal neoplasms with good outcome. However, if bowel lies adjacent to a tumor, ablation increases the risk of thermal bowel injury, and the consequences could be fatal. We describe the technique, effectiveness and safety of using thermo sensitive hydrogel as insulation to displace the bowel away during PRFA. MATERIALS AND METHODS: The study was divided into two main parts: the in vitro and in vivo studies. In in vitro study, to explore the heat insulation of hydrogel, the rabbit kidney was entirely embedded in hydrogel, and then radiofrequency ablation was performed; the temperature on the gel-air and gel kidney interfaces was measured. In in vivo study, hydrogel of poloxamer 407, 25 % concentration (w/v), was instilled into the perinephric space of 10 rabbits under CT guidance to separate the kidney from adjacent bowel before PRFA performed in the targeted parenchyma in the gel group. For the control group, PRFA was performed in similar portions of 10 rabbits without instillation of hydrogel. Some parameters were recorded such as kidney-to-bowel and electrode-to-bowel distance. Immediately after PRFA, distribution of hydrogel was evaluated and the dimension of radiofrequency ablation zone was measured; bowel thermal injury was compared between the gel and control groups by gross anatomy and histopathological examination. To assess safety, two additional follow-up groups with 10 rabbits in each were set; after PRFA, CT scan was performed every 2 days; gel absorption, thermal damage and some other complications were evaluated during the period. RESULTS AND CONCLUSIONS: In in vitro study, temperature was significantly lower at the gel-air than gel-kidney interface (P < .05), and the temperature gradient was positively associated with gel thickness. In in vivo study, hydrogel was instilled successfully in all rabbits in the gel group. The kidney-to-bowel and electrode-to-bowel distances were larger in the gel than control group [(1.1 +/- 0.6 cm vs 0.1 +/- 0.0 cm, P < .01), (1.8 +/- 0.4 cm vs 0.5 +/- 0.1 cm, P < .01), respectively]. The gel and control groups did not differ in size of the ablation zones (0.80 +/- 0.2 cm vs 0.75 +/- 0.3 cm, P > .05). Thermal injury in adjacent bowel was more serious in the control than gel group (P < .01). As for the follow-up, rabbits with gel instillation showed good condition and gel was absorbed gradually within 5 days. Those rabbits with no bowel displacement by gel got significantly lower survival rate and high complication rate (P < .01). CONCLUSION: Hydrogel-dissection by means of thermo sensitive hydrogel instillation is valuable for protecting the bowel adjacent to ablation area against thermal injury during PRFA. PMID- 27394138 TI - Grit, Gravity & Grace: New Poems about Medicine and Healthcare, edited by Rhonda Soricelli and Jack Coulehan, The College of Physicians of Philadelphia, 2015. PMID- 27394139 TI - Assessment of the SonixGPS system for its application in real-time ultrasonography navigation-guided percutaneous nephrolithotomy for the treatment of complex kidney stones. AB - SonixGPS is a novel real-time ultrasonography navigation technology, which has been demonstrated to promote accuracy of puncture in surgical operations. The aim of this study is to evaluate its application in guiding the puncture during percutaneous nephrolithotomy (PCNL). We retrospectively reviewed our experience in treating a total of 74 patients with complex kidney stones with PCNL, in which puncture in 37 cases were guided by SonixGPS system, while the other 37 by conventional ultrasound. The effectiveness of operation was evaluated in terms of stone clearance rate, operation time, time to successful puncture, number of attempts for successful puncture and hospital stay. The safety of operation was examined by evaluating postoperative complications. Our retrospective review showed that although there were no significant differences in stone clearance rates between the groups, SonixGPS guidance resulted in more puncture accuracy with shorter puncture time and higher successful puncture rate. Under the help of SonixGPS, most patients (92 %) had no or just mild complications, compared to that (73 %) in conventional ultrasound group. Post-operative decrease of hemoglobin in SonixGPS group was 13.79 (7-33) mg/dl, significantly lower than that 20.97 (8-41) mg/dl in conventional ultrasound group. Our experience demonstrates that SonixGPS is superior to conventional ultrasound in guiding the puncture in PCNL for the treatment of complex kidney stone. PMID- 27394140 TI - The enzyme profiles in the connective tissue attaching pin bones to the surrounding tissue is specific in farmed salmon (Salmo salar) and cod (Gadus morhua L.). AB - Post mortem storage is a necessary process for removal of pin bones without destruction of fillets, thereby avoiding volume and economic loss. However, the enzymes involved in loosening pin bones during storage have not been studied to a great extent. In this study, the activities and localization of MMPs in the connective tissue (CT) of pin bones dissected from fillet of salmon and cod were investigated. Interestingly, the enzyme activity profile in these two species was different during post mortem storage of fish fillets. Adding MMP inhibitor (GM6001) and serine protease inhibitor (Pefabloc) revealed different effects in the two species, suggesting different regulations in salmon and cod. In situ zymography with the same inhibitors verified MMP and serine protease activity in CT close to pin bone at early post mortem (6 h) in salmon. However, MMP inhibition was not evident in cod in this area at that time point. Immunohistochemistry further revealed MMP9 and MMP13 were located more to the outer rim of CT, facing the pin bone and adipose tissue, while MMP7 was more randomly distributed within CT in salmon. In contrast, all these three MMPs were randomly distributed in CT in cod. In summary, our study reveals different MMP enzyme profiles in salmon and cod in the pin bone area, influenced by serine proteases, and suggests that MMPs and serine proteases must be taken in consideration when studying the conditions for early pin bone removal. PMID- 27394141 TI - Dissecting the interaction between transglutaminase 2 and fibronectin. AB - In the extracellular environment, the enzyme transglutaminase 2 (TG2) is involved in cell-matrix interactions through association with the extracellular matrix protein, fibronectin (FN). The 45 kDa gelatin-binding domain of FN (45FN) is responsible for the binding to TG2. Previous studies have demonstrated that the FN-binding site of TG2 is located in the N-terminal domain of the enzyme although with conflicting results regarding the specific residues involved. Here we have mapped the FN interaction site of human TG2 by use of hydrogen/deuterium exchange coupled with mass spectrometry, and we confirm that the FN-binding site is located in the N-terminal domain of TG2. Furthermore, by combination of site directed mutagenesis and surface plasmon resonance analysis we have identified the TG2 residues K30, R116 and H134 as crucial to maintain the high affinity interaction with FN. Mutation of all three residues simultaneously reduced binding to 45FN by more than 2000-fold. We also identified residues in the catalytic core domain of TG2 that contributed to FN binding, hence extending the binding interface between TG2 and FN. This study provides new insights into the high affinity interaction between TG2 and FN. PMID- 27394142 TI - Inter-molecular crosslinking activity is engendered by the dimeric form of transglutaminase 2. AB - Transglutaminase 2 (TGase 2) catalyzes a crosslink between protein bound glutamine and -lysine. We proposed the mechanism of TGase 2 activation depends on conformation change from unfolded monomer to unfolded dimer. We found that TGase 2 has temperature-sensitive conformation change system at 30 degrees C. Small angle X-ray scattering analysis showed that the enzyme was maintained as an unfolded monomer at temperatures below 30 degrees C, but changed to an unfolded dimer at over 30 degrees C. Mass analysis revealed that the C-terminus of TGase 2 was the critical region for dimerization. Furthermore, this conformational switch creates new biochemical reactivity that catalyzed inter-molecular crosslink at above 30 degrees C as an unfolded dimer of TGase 2 while catalyzed intra-molecular crosslink at below 30 degrees C as an unfolded monomer of TGase 2. The mechanism of TGase 2 activation depends on temperature-sensitive conformation change from unfolded monomer to unfolded dimer at over 30 degrees C. Furthermore, inter-molecular crosslinking activity is generated by the dimeric form of TGase 2. TGase 2 switches its conformation from a monomer to a dimer following a change in temperature, which engendered unique catalytic function of enzyme as inter-molecular crosslinking activity with calcium. PMID- 27394143 TI - Arthroscopic meniscectomy of traumatic versus atraumatic tears in middle aged patients: is there a difference? AB - INTRODUCTION: Meniscal tears can be classified in various ways, one of which is into traumatic or degenerative. It is not known whether partial meniscectomy of clinically defined traumatic compared to degenerative tears in middle age patients has favorable results. The purpose of this study was to compare the outcome after arthroscopic partial meniscectomy of clinically defined traumatic to degenerative meniscal tears in middle age patients. MATERIALS AND METHODS: Eighty-six middle aged patients with stable knees and no radiographic signs of osteoarthritis who had arthroscopic partial meniscectomy were divided into a study group of 43 patients with a preceding knee injury related to their knee symptoms (traumatic group) and a control group of 43 uninjured patients (atraumatic group), matched by age, sex, body mass index and comorbidities. The surgical findings and postoperative clinical scores were compared between the two groups. RESULTS: There were no statistical differences in surgical findings of tear types and degree of chondral lesions. At the end of the follow-up 33 (77 %) patients in each group were satisfied to have had the operation. The median Lysholm score improved from 65.9 +/- 17.4 to 77.4 +/- 21.2 points (P = 0.001) in the traumatic group and from 65.3 +/- 17 to 82.4 +/- 17.7 in the atraumatic group (P < 0.0001). CONCLUSIONS: Arthroscopic partial meniscectomy in middle aged patients with stable knees and no signs of radiographic osteoarthritis improve pain and function. There were no differences in surgical findings and short term clinical outcome between patients with and without preceding knee injury. PMID- 27394144 TI - Clinical outcomes after arthroscopic acetabular labral repair using knot-tying or knotless suture technique. AB - BACKGROUND: The purpose of the study was to compare the clinical results of arthroscopic labral repair using knot-tying and knotless suture anchor techniques for patients with labral tears. METHODS: From September 2012 to May 2013, we performed a randomized, prospective analysis of 40 hips with labral tears treated with arthroscopic labral repair via knot-tying (group A) or knotless suture anchors (group B). A total of 33 patients were treated for labral tears, and 7 of them received bilateral labral repair. Outcomes and intraoperative parameters were prospectively measured with the UCLA score, the modified Harris Hip Score (MHHS), the Hip disability and Osteoarthritis Outcome Score (HOOS), and the Hip Outcome Score (HOS). RESULTS: Three patients (3 hips) were lost to follow up. A total of 37 hips (30 patients) were finally analyzed: 19 hips in group A and 18 in group B. The mean traction time for group A and group B was 72.2 versus 68.7 min, respectively (p = 0.314). Although the clinical outcome scores in both groups improved between the initial and final visits, there was no difference in measurements parameters between the two groups. Survival rate, using reoperation or progression of osteoarthritis as the primary end points, was 100 %. 83 % of cases had excellent and good MHHS scores after 2 years of follow-up. During arthroscopic surgery, the drill penetrated the closing subchondral area or the joint in three hips. There was no progression of arthritic change at the latest follow-up. CONCLUSIONS: Labral repair with either knot-tying or knotless suture anchor resulted in significant postoperative improvements and no difference between the two groups after 2 years of follow-up. PMID- 27394145 TI - Prevalence and infection intensity of Rickettsia massiliae in Rhipicephalus sanguineus sensu lato ticks from Mendoza, Argentina. AB - Rickettsia massiliae belongs to the spotted fever group and in the New World is commonly associated with the brown dog tick, Rhipicephalus sanguineus. Herein we investigate the presence of R. massiliae in Rh. sanguineus sensu lato ticks in a location near the Andean foothills (Mendoza, Argentina), to provide a prevalence estimate and to assess the infection intensity of this pathogen. Rickettsia massiliae infection was found in 5.1% of the Rh. sanguineus s.l ticks analyzed, all with high infection intensities. Molecular analysis determined that all R. massiliae-infected Rh. sanguineus s.l. ticks belonged to the temperate lineage. PMID- 27394146 TI - Mucosal delivery of a combination adjuvant comprising emulsified fine particles and LD-indolicidin enhances serological immunity to inactivated influenza virus. AB - Here we investigate the immunogenicity of a combination adjuvant comprising emulsified fine particles (namely PELC) together with LD-indolicidin, a peptiomimetic stereoisomer of the bovine neutrophil peptide indolicidin. We demonstrated that intranasal vaccination with either PELC/LD-indolicidin or Alum enhances protective influenza-specific serological immunity in mice; however, the adjuvant potency of Alum was rather reduced when the mice vaccinated orally with formulated influenza vaccines. The information gathered from this study will enhance our effort in the formulation design as well as the optimization of alternative administration routes for prophylactic vaccines against emerging infectious diseases, in particular pandemic influenza. PMID- 27394147 TI - Patterns of striatal functional connectivity differ in early and late onset Parkinson's disease. AB - To map functional connectivity (FC) patterns of early onset Parkinson's disease (EOPD) and late onset PD (LOPD) in drug-naive early stage. MRI was used to assess atrophy and resting-state FC focusing on striatal subregions of EOPD and LOPD in two subgroups of 18 patients matched for disease duration and severity, relative to age- and sex- matched healthy controls. Compared with controls, both PD subgroups showed FC alterations in cortico-striatal and cerebello-striatal loops but with different patterns in resting state. EOPD patients showed widespread increased FC between striatum and sensorimotor cortex, middle frontal gyrus, superior and inferior parietal lobules, superior and inferior temporal gyri, and cerebellum. While LOPD patients were evidenced with increased FC in cerebello striatal circuit and decreased FC between orbitofrontal gyrus and striatum. In addition, Unified Parkinson's Disease Rating Scale part III scores were negatively correlated with the increased FC between the caudate nucleus and sensorimotor cortex (r = -0.571, p = 0.013) in EOPD patients, while negatively correlated with the increased FC between the putamen and cerebellum (r = -0.478, p = 0.045) in LOPD patients, suggesting that increased FC is here likely to reflect compensatory mechanism. FC changes in EOPD and LOPD share common features and have differences, which may suggest that the responses to defective basal ganglia are different between the two subtypes. Improved insights into the onset related subtypes of PD and its disruptive FC pattern will be valuable for improving our understanding of the pathogenesis of the disease. PMID- 27394148 TI - Association between age, substance use, and outcomes in Medicare enrollees with prostate cancer. AB - OBJECTIVE: To analyze the association between age, substance use, and outcomes in fee-for-service Medicare enrollees with advanced prostate cancer. METHODS: Retrospective longitudinal cohort study of elderly men diagnosed with advanced prostate cancer using SEER-Medicare data between 2000 and 2009. Substance use disorder was identified using claims for alcoholic psychosis, drug psychoses, alcohol dependence syndrome, drug dependence, and non-dependent use of drugs. We compared health service use, cost, and 5-year mortality across two age-groups: young-old (66-74years) and old-old (>= 75years). RESULTS: Cohort consisted of 8484 young-old and 5763 old-old patients with advanced prostate cancer. Prevalence of substance use was 12.4% in young-old and 7.4% in old-old group. For the young-old group, the 'drug psychoses and related' category had the highest inpatient, outpatient, and ER usage as well as the highest hazard of mortality (HR=2.2; CI=1.5, 3.1), compared to those without substance use. Compared to the no substance use group, those with substance use in the follow-up phase had higher inpatient and ER visits, and those with substance use in treatment phase had higher outpatient visits and highest hazard of mortality (HR=1.6; CI=1.4, 1.9). For the old-old group, the 'drug psychoses and related' category was associated with highest inpatient and outpatient use; and 'Non-dependent use of drugs' were associated with highest ER use, compared to those without substance use. CONCLUSION: Intersection of cancer and substance use disorder in elderly patients with advanced prostate cancer covered by Medicare is age specific. An integrated and multidisciplinary approach to screen, refer, and treat substance use in patients with prostate cancer may improve outcomes and reduce costs. PMID- 27394149 TI - Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study. AB - BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1beta+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL 1beta+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates. PMID- 27394150 TI - Brain connections of words, perceptions and actions: A neurobiological model of spatio-temporal semantic activation in the human cortex. AB - Neuroimaging and patient studies show that different areas of cortex respectively specialize for general and selective, or category-specific, semantic processing. Why are there both semantic hubs and category-specificity, and how come that they emerge in different cortical regions? Can the activation time-course of these areas be predicted and explained by brain-like network models? In this present work, we extend a neurocomputational model of human cortical function to simulate the time-course of cortical processes of understanding meaningful concrete words. The model implements frontal and temporal cortical areas for language, perception, and action along with their connectivity. It uses Hebbian learning to semantically ground words in aspects of their referential object- and action related meaning. Compared with earlier proposals, the present model incorporates additional neuroanatomical links supported by connectivity studies and downscaled synaptic weights in order to control for functional between-area differences purely due to the number of in- or output links of an area. We show that learning of semantic relationships between words and the objects and actions these symbols are used to speak about, leads to the formation of distributed circuits, which all include neuronal material in connector hub areas bridging between sensory and motor cortical systems. Therefore, these connector hub areas acquire a role as semantic hubs. By differentially reaching into motor or visual areas, the cortical distributions of the emergent 'semantic circuits' reflect aspects of the represented symbols' meaning, thus explaining category-specificity. The improved connectivity structure of our model entails a degree of category-specificity even in the 'semantic hubs' of the model. The relative time-course of activation of these areas is typically fast and near-simultaneous, with semantic hubs central to the network structure activating before modality-preferential areas carrying semantic information. PMID- 27394151 TI - Category learning in Alzheimer's disease and normal cognitive aging depends on initial experience of feature variability. AB - Semantic category learning is dependent upon several factors, including the nature of the learning task, as well as individual differences in the quality and heterogeneity of exemplars that an individual encounters during learning. We trained healthy older adults (n=39) and individuals with a diagnosis of Alzheimer's disease or Mild Cognitive Impairment (n=44) to recognize instances of a fictitious animal, a "crutter". Each stimulus item contained 10 visual features (e.g., color, tail shape) which took one of two values for each feature (e.g., yellow/red, curly/straight tails). Participants were presented with a series of items (learning phase) and were either told the items belonged to a semantic category (explicit condition) or were told to think about the appearance of the items (implicit condition). Half of participants saw learning items with higher similarity to an unseen prototype (high typicality learning set), and thus lower between-item variability in their constituent features; the other half learned from items with lower typicality (low typicality learning set) and higher between item feature variability. After the learning phase, participants were presented with test items one at a time that varied in the number of typical features from 0 (antitype) to 10 (prototype). We examined between-subjects factors of learning set (lower or higher typicality), instruction type (explicit or implicit), and group (patients vs. elderly control). Learning in controls was aided by higher learning set typicality: while controls in both learning set groups demonstrated significant learning, those exposed to a high-typicality learning set appeared to develop a prototype that helped guide their category membership judgments. Overall, patients demonstrated more difficulty with category learning than elderly controls. Patients exposed to the higher-typicality learning set were sensitive to the typical features of the category and discriminated between the most and least typical test items, although less reliably than controls. In contrast, patients exposed to the low-typicality learning set showed no evidence of learning. Analysis of structural imaging data indicated a positive association between left hippocampal grey matter density in elderly controls but a negative association in the patient group, suggesting differential reliance on hippocampal mediated learning. Contrary to hypotheses, learning did not differ between explicit and implicit conditions for either group. Results demonstrate that category learning is improved when learning materials are highly similar to the prototype. PMID- 27394152 TI - Hidden sources of joy, fear, and sadness: Explicit versus implicit neural processing of musical emotions. AB - Music is often used to regulate emotions and mood. Typically, music conveys and induces emotions even when one does not attend to them. Studies on the neural substrates of musical emotions have, however, only examined brain activity when subjects have focused on the emotional content of the music. Here we address with functional magnetic resonance imaging (fMRI) the neural processing of happy, sad, and fearful music with a paradigm in which 56 subjects were instructed to either classify the emotions (explicit condition) or pay attention to the number of instruments playing (implicit condition) in 4-s music clips. In the implicit vs. explicit condition, stimuli activated bilaterally the inferior parietal lobule, premotor cortex, caudate, and ventromedial frontal areas. The cortical dorsomedial prefrontal and occipital areas activated during explicit processing were those previously shown to be associated with the cognitive processing of music and emotion recognition and regulation. Moreover, happiness in music was associated with activity in the bilateral auditory cortex, left parahippocampal gyrus, and supplementary motor area, whereas the negative emotions of sadness and fear corresponded with activation of the left anterior cingulate and middle frontal gyrus and down-regulation of the orbitofrontal cortex. Our study demonstrates for the first time in healthy subjects the neural underpinnings of the implicit processing of brief musical emotions, particularly in frontoparietal, dorsolateral prefrontal, and striatal areas of the brain. PMID- 27394153 TI - Different expression and subcellular localization of Phosphoinositide-specific Phospholipase C enzymes in differently polarized macrophages. AB - Macrophages' phenotypic and functional diversity depends on differentiating programs related to local environmental factors. Recent interest was deserved to the signal transduction pathways acting in macrophage polarization, including the phosphoinositide (PI) system and related phospholipase C (PLC) family of enzymes. The expression panel of PLCs and the subcellular localization differs in quiescent cells compared to the pathological counterpart. We analyzed the expression of PLC enzymes in unpolarized (M0), as well as in M1 and M2 macrophages to list the expressed isoforms and their subcellular localization. Furthermore, we investigated whether inflammatory stimulation modified the basal panel of PLCs' expression and subcellular localization. All PLC enzymes were detected within both M1 and M2 cells, but not in M0 cells. M0, as well as M1 and M2 cells own a specific panel of expression, different for both genes' mRNA expression and intracellular localization of PLC enzymes. The panel of PLC genes' expression and PLC proteins' presence slightly changes after inflammatory stimulation. PLC enzymes might play a complex role in macrophages during inflammation and probably also during polarization. PMID- 27394154 TI - Immunolocalization of cyclotides in plant cells, tissues and organ supports their role in host defense. AB - MAIN CONCLUSION: The distribution of cyclotides was visualized in plant cells, tissues and organs using immunohistochemistry. Finding of cyclotides in tissues potentially vulnerable to pathogen attacks supports their role as defense molecules. The cyclotide family of plant peptides is characterized by the cyclic cystine knot motif and its diverse biological activities. Given their insecticidal and antimicrobial properties, the role of cyclotides in planta is probably associated with host defense. Our current understanding of the cellular compartmentalization of cyclotides in the vacuole is based on indirect studies on transgenic model plants that do not express cyclotides naturally. Matrix-assisted laser desorption ionization (MALDI) imaging has also been used to study the distribution of cyclotides, but the technique's resolution was insufficient to determine their tissue or cell distribution. To avoid the limitations of these approaches, immunohistochemical visualization methods were used. Antibodies were raised in rabbits using cycloviolacin O2 (cyO2), and their specificity was determined by Western and dot blot experiments. Slides for immunohistochemical analysis were prepared from leaf, petiole and root fragments of Viola odorata and Viola uliginosa, and specimens were visualized using indirect epifluorescence microscopy. The antibodies against cyclotides were specific against selected bracelet cyclotides with high similarity (cyO2, cyO3, cyO8, cyO13) and suitable for immunohistochemistry. The tissue distribution of the cyclotides visualized in this way is consistent with their proposed role in host defense-relatively large quantities were observed in the leaf and petiole epidermis in both Viola species. Cyclotides were also found in vascular tissue in all the assessed plant organs. The vacuole storage of cyclotides was directly shown. PMID- 27394156 TI - EGIST: a Rare Tumor. PMID- 27394155 TI - Simultaneous regulation of antenna size and photosystem I/II stoichiometry in Arabidopsis thaliana. AB - MAIN CONCLUSION: The photosystem I/II ratio increased when antenna size was enlarged by transient induction of CAO in chlorophyll b -less mutants, thus indicating simultaneous regulation of antenna size and photosystem I/II stoichiometry. Regulation of antenna size and photosystem I/II stoichiometry is an indispensable strategy for plants to acclimate to changes to light environments. When plants grown in high-light conditions are transferred to low light conditions, the peripheral antennae of photosystems are enlarged. A change in the photosystem I/II ratio is also observed under the same light conditions. However, our knowledge of the correlation between antenna size modulation and variation in photosystem I/II stoichiometry remains limited. In this study, chlorophyll a oxygenase was transiently induced in Arabidopsis thaliana chlorophyll b-less mutants, ch1-1, to alter the antenna size without changing environmental conditions. In addition to the accumulation of chlorophyll b, the levels of the peripheral antenna complexes of both photosystems gradually increased, and these were assembled to the core antenna of both photosystems. However, the antenna size of photosystem II was greater than that of photosystem I. Immunoblot analysis of core antenna proteins showed that the number of photosystem I increased, but not that of photosystem II, resulting in an increase in the photosystem I/II ratio. These results clearly indicate that antenna size adjustment was coupled with changes in photosystem I/II stoichiometry. Based on these results, the physiological importance of simultaneous regulation of antenna size and photosystem I/II stoichiometry is discussed in relation to acclimation to light conditions. PMID- 27394157 TI - Lumacaftor/Ivacaftor: A Review in Cystic Fibrosis. AB - Lumacaftor/ivacaftor (OrkambiTM) is a fixed-dose tablet containing a corrector (lumacaftor) and potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (aged >=12 years) homozygous for the most common CFTR mutation, F508del. Lumacaftor improves the processing of F508del CFTR and its transport to the cell surface, while ivacaftor increases the channel's open probability and transport of chloride. In two 24-week trials in the approved patient population (TRAFFIC and TRANSPORT), lumacaftor 400 mg plus ivacaftor 250 mg, administered every 12 h in combination with standard therapy, was associated with an ~3 % statistically significant improvement in lung function relative to placebo (as measured by the percent predicted forced expiratory volume in 1 s). Lumacaftor plus ivacaftor did not significantly improve respiratory symptoms, although reduced pulmonary exacerbations to a clinically meaningful extent and, in one trial (TRANSPORT), significantly improved body mass index (BMI). In an ongoing extension of these studies (PROGRESS), lumacaftor plus ivacaftor provided clinical benefit over a further 72 weeks of treatment. Lumacaftor plus ivacaftor had an acceptable tolerability profile, with the most common adverse events being respiratory or gastrointestinal in nature. Thus, lumacaftor/ivacaftor expands the treatment options available for patients with cystic fibrosis homozygous for the F508del CFTR mutation, although its precise place in clinical practice remains to be determined. PMID- 27394158 TI - Molecular detection of common intestinal parasites: a performance evaluation of the BD MaxTM Enteric Parasite Panel. AB - The purpose of this study was to evaluate the level of agreement of the BD MaxTM Enteric Parasite Panel (EPP) with microscopy for the detection of Giardia duodenalis, Cryptosporidium spp. and Entamoeba histolytica in stool samples. A total of 372 stool samples (partly collected on the basis of positive microscopy and partly unselected, consecutive sample submitted for parasite investigation) were tested with EPP according to manufacturer's instructions and also using microscopy according to standard techniques. Discrepant samples were further tested using PCR by the National Parasitology reference laboratory. Levels of agreement and laboratory turnaround times were measured and compared. Overall, positive and negative percent agreement was high between the two methods. However, microscopy resulted in four false positives and one false negative for G. duodenalis and two false positives for Cryptosporidium. Additionally, microscopy could not differentiate between E. histolytica and Entamoeba dispar. Median laboratory turnaround time was 65 hours for microscopy; results from EPP could be available after four hours. Blastocycstis hominis was detected by microscopy in one sample and would have been missed if only EPP was performed. The EPP was a good alternative to microscopy, detecting a small number of additional positives that were missed by microscopy. The assay is significantly faster than microscopy and allows laboratory workflows to be streamlined. The risk of missing parasites that are not included in the EPP appears to be minimal in the studied population; however, there may be certain patient groups who would benefit from microscopic examination of stools. PMID- 27394159 TI - Simple risk stratification score for prognosis of syncope. AB - PURPOSE: The aim of this study is to describe a new simple score to predict the occurrence of severe adverse events in patients admitted for syncope to a tertiary cardiology referral center. METHODS: Three hundred ninety-three subjects with emergency department visits for syncope were identified and followed prospectively. The primary endpoint was death or unplanned hospital admission after the syncopal episode. The score consisted of sum of the following: previous syncope (2 points), an abnormal electrocardiogram (3 points), and history of heart disease (4 points). The accuracy of our score was compared to other scores available in the literature. RESULTS: Of the 393 subjects, 87 were diagnosed with syncope secondary to structural or electrical heart disease and 306 with noncardiac syncope. The primary endpoint occurred in 202 cases, including death occurring in 25 patients during the 12-month follow-up. The 30-day event rate for the primary endpoint was 26.5 %. The c-statistic for the new score was 0.76 (95 % CI 0.71-0.80) similar to other scores when applied to our sample. Patients with a score of 3 out of 9 had a hazard ratio of 3.46 (95 % CI 1.22-6.11) for death during the follow-up. CONCLUSIONS: In the study population, the new syncope score detected patients with an increased risk of death after discharge from a syncopal event. Our score predicted adverse events comparably to other scores reported in the literature. It has the advantage of being simple and easily obtained from the history and an inexpensive noninvasive test-the ECG. PMID- 27394160 TI - Experience with bisoprolol in long-QT1 and long-QT2 syndrome. AB - BACKGROUND: The protective effect of beta-blockers in patients with inherited Long-QT syndrome is well established. Recent reports have suggested that beta blockers are not equally effective in Long-QT (LQT). Bisoprolol is an attractive candidate for use in LQT because of its cardioselective properties and favorable side-effect profile. METHODS: We performed a retrospective cohort study of 114 consecutive patients with gene-positive Long-QT syndrome type 1 (LQT1) or Long-QT syndrome type 2 (LQT2) treated with bisoprolol, nadolol or atenolol with a total of 580 person-years of follow-up. Electrocardiogram (ECG) parameters and cardiac events during follow-up were compared. In addition, exercise treadmill testing was performed in bisoprolol-treated patients. RESULTS: Fifty-nine patients were treated with bisoprolol, 39 with atenolol and 16 with nadolol. Overall, 59 % were females and 62 % had LQT1. Baseline heart rate and corrected QT (QTc) interval were similar between the groups. QTc shortening was observed in individuals on bisoprolol (DeltaQTc -5 +/- 31 ms; p = 0.049) and nadolol (DeltaQTc -13 +/- 16 ms; p = 0.02) but not on atenolol (DeltaQTc +9 +/- 24 ms; p = 0.16). Median follow-up was similar for bisoprolol and nadolol (3 years), but longer for atenolol (6 years; p = 0.03); one cardiac event occurred in the bisoprolol group (1.7 %) and two events occurred in the atenolol group (5.1 %; p = 0.45), whereas none occurred in nadolol-treated patients. Beta-blocker efficacy was not affected by the underlying genotype. The antiadrenergic effect of bisoprolol correlated with the reduction of peak heart rates at exercise testing. CONCLUSIONS: Bisoprolol treatment results in QTc shortening in gene-positive LQT1 and LQT2 patients and is well tolerated during long-term administration. The equivalence of bisoprolol for protection from ventricular arrhythmia in LQT patients compared to established beta-blockers remains unknown. Further large-scale studies are required. PMID- 27394162 TI - Adhesion and cytotoxicity of Aeromonas caviae to rabbit intestinal epithelium ex vivo. AB - Aeromonads are considered potential pathogens for humans and animals and are responsible for the etiology of intestinal and extraintestinal diseases. The presence of Aeromonas spp. in food and water shows that it is an important vehicle of infection in humans. The pathology caused by these bacteria involves several virulence factors, such as the ability to produce toxins, adhesion and invasion. The present study investigated the interaction of five Aeromonas caviae strains isolated from human diarrheic faeces with rabbit ileal and colonic mucosa ex vivo, using in vitro organ culture model. The in vitro adhesion assays using cultured tissue were performed with A. caviae strains co-incubated with intestinal fragments of ileum and colon over a period of 6 h. The fragments were analyzed by light and electron microscopy. All strains adhered to rabbit ileal and colonic mucosa ex vivo, with higher degree of adherence presented on colonic mucosa. The typical aggregative adherence pattern was observed among strains studied. Through electron and light microscopy, we observed extensive colonization of ileal and colonic mucosa, large mucus production, biofilm formation and morphological alterations such as intense vacuolization, structural disorganization, cell extrusion and destruction of the villi. These results demonstrate that in vitro organ culture of intestinal mucosa from rabbit may be used to investigate Aeromonas spp. PATHOGENESIS: Finally, our results support the pathogenic potential of Aeromonas emphasising their importance in public health. PMID- 27394161 TI - Hybrid anisotropic nanostructures for dual-modal cancer imaging and image-guided chemo-thermo therapies. AB - The multimodality theranostic system, which can integrate two or more different therapeutic modalities and multimodal imaging agents into a nanoentity, shows great promising prospects for the cancer treatment. Herein, we developed an efficient and novel strategy to synthesize hybrid anisotropic nanoparticles (HANs) with intrinsic multimodal theranostic capability [chemotherapy, photothermal therapy, magnetic resonance imaging (MRI), and photoacoustic imaging (PAI)]. For the first time, under the guidance of MRI and PAI, the chemotherapy and thermotherapy induced by administration of multifunctional hybrid nanoprobes were applied simultaneously to the treatment of colon cancer-bearing mice in vivo. PMID- 27394164 TI - Demyelinating strain of mouse hepatitis virus infection bridging innate and adaptive immune response in the induction of demyelination. AB - The presence of immunoglobulin oligoclonal bands in the cerebrospinal fluid of Multiple Sclerosis (MS) patients supports the hypothesis of an infectious etiology, although the antigenic targets remain elusive. Neurotropic mouse hepatitis virus (MHV) infection in mice provides a useful tool for studying mechanisms of demyelination in a virus-induced experimental model of MS. This study uses Affymetrix microarray analysis to compare differential spinal cord mRNA levels between mice infected with demyelinating and non-demyelinating strains of MHV to identify host immune genes expressed in this demyelinating disease model. The study reveals that during the acute stage of infection, both strains induce inflammatory innate immune response genes, whereas upregulation of several immunoglobulin genes during chronic stage infection is unique to infection with the demyelinating strain. Results suggest that the demyelinating strain induced an innate-immune response during acute infection that may promote switching of Ig isotype genes during chronic infection, potentially playing a role in antibody-mediated progressive demyelination even after viral clearance. PMID- 27394165 TI - gr-MRI: A software package for magnetic resonance imaging using software defined radios. AB - The goal of this work is to develop software that enables the rapid implementation of custom MRI spectrometers using commercially-available software defined radios (SDRs). The developed gr-MRI software package comprises a set of Python scripts, flowgraphs, and signal generation and recording blocks for GNU Radio, an open-source SDR software package that is widely used in communications research. gr-MRI implements basic event sequencing functionality, and tools for system calibrations, multi-radio synchronization, and MR signal processing and image reconstruction. It includes four pulse sequences: a single-pulse sequence to record free induction signals, a gradient-recalled echo imaging sequence, a spin echo imaging sequence, and an inversion recovery spin echo imaging sequence. The sequences were used to perform phantom imaging scans with a 0.5Tesla tabletop MRI scanner and two commercially-available SDRs. One SDR was used for RF excitation and reception, and the other for gradient pulse generation. The total SDR hardware cost was approximately $2000. The frequency of radio desynchronization events and the frequency with which the software recovered from those events was also measured, and the SDR's ability to generate frequency-swept RF waveforms was validated and compared to the scanner's commercial spectrometer. The spin echo images geometrically matched those acquired using the commercial spectrometer, with no unexpected distortions. Desynchronization events were more likely to occur at the very beginning of an imaging scan, but were nearly eliminated if the user invoked the sequence for a short period before beginning data recording. The SDR produced a 500kHz bandwidth frequency-swept pulse with high fidelity, while the commercial spectrometer produced a waveform with large frequency spike errors. In conclusion, the developed gr-MRI software can be used to develop high-fidelity, low-cost custom MRI spectrometers using commercially available SDRs. PMID- 27394168 TI - Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: New nanotools for cancer treatment. AB - Exosomes are naturally secreted nanovesicles that have recently aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. These 30-100nm sized vesicles are released from the cells into the extracellular space and ultimately into biofluids in a tightly regulated way. Their molecular composition reflects their cells of origin, may confer specific cell or tissue tropism and underlines their biological activity. Exosomes and other extracellular vesicles (EVs) carry specific sets of proteins, nucleic acids (DNA, mRNA and regulatory RNAs), lipids and metabolites that represent an appealing source of novel noninvasive markers through biofluid biopsies. Exosome shuttled molecules maintain their biological activity and are capable of modulating and reprogramming recipient cells. This multi-faceted nature of exosomes hold great promise for improving cancer treatment featuring them as novel diagnostic sensors as well as therapeutic effectors and drug delivery vectors. Natural biological activity including the therapeutic payload and targeting behavior of EVs can be tuned via genetic and chemical engineering. In this review we describe the properties that EVs share with conventional synthetic nanoparticles, including size, liposome-like membrane bilayer with customizable surface, and multifunctional capacity. We also highlight unique characteristics of EVs, which possibly allow them to circumvent some limitations of synthetic nanoparticle systems and facilitate clinical translation. The latter are in particular correlated with their innate stability, ability to cross biological barriers, efficiently deliver bioactive cargos or evade immune recognition. Furthermore, we discuss the potential roles for EVs in diagnostics and theranostics, and highlight the challenges that still need to be overcome before EVs can be applied to routine clinical practice. PMID- 27394169 TI - Early neurodevelopmental outcomes of infants with intestinal failure. AB - BACKGROUND: The survival rate of infants and children with intestinal failure is increasing, necessitating a greater focus on their developmental trajectory. AIMS: To evaluate neurodevelopmental outcomes in children with intestinal failure at 0-15months corrected age. STUDY DESIGN: Analysis of clinical, demographic and developmental assessment results of 33 children followed in an intestinal rehabilitation program between 2011 and 2014. Outcome measures included: Prechtl's Assessment of General Movements, Movement Assessment of Infants, Alberta Infant Motor Scale and Mullen Scales of Early Learning. Clinical factors were correlated with poorer developmental outcomes at 12-15months corrected age. RESULTS: Thirty-three infants (17 males), median gestational age 34weeks (interquartile range 29.5-36.0) with birth weight 1.98kg (interquartile range 1.17-2.50). Twenty-nine (88%) infants had abnormal General Movements. More than half had suspect or abnormal scores on the Alberta Infant Motor Scale and medium to high-risk scores for future neuromotor delay on the Movement Assessment of Infants. Delays were seen across all Mullen subscales, most notably in gross motor skills. Factors significantly associated with poorer outcomes at 12 15months included: prematurity, low birth weight, central nervous system co morbidity, longer neonatal intensive care admission, necrotizing enterocolitis diagnosis, number of operations and conjugated hyperbilirubinemia. CONCLUSION: Multiple risk factors contribute to early developmental delay in children with intestinal failure, highlighting the importance of close developmental follow-up. PMID- 27394166 TI - Friend or foe? Telomerase as a pharmacological target in cancer and cardiovascular disease. AB - Aging, cancer, and chronic disease have remained at the forefront of basic biological research for decades. Within this context, significant attention has been paid to the role of telomerase, the enzyme responsible for lengthening telomeres, the nucleotide sequences located at the end of chromosomes found in the nucleus. Alterations in telomere length and telomerase activity are a common denominator to the underlying pathology of these diseases. While nuclear specific, telomere-lengthening effects of telomerase impact cellular/organismal aging and cancer development, non-canonical, extra-nuclear, and non-telomere lengthening contributions of telomerase have only recently been described and their exact physiological implications are ill defined. Although the mechanism remains unclear, recent reports reveal that the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), regulates levels of mitochondrial derived reactive oxygen species (mtROS), independent of its established role in the nucleus. Telomerase inhibition has been the target of chemotherapy (directed or indirectly) for over a decade now, yet no telomerase inhibitor is FDA approved and few are currently in late-stage clinical trials, possibly due to underappreciation of the distinct extra-nuclear functions of telomerase. Moreover, evaluation of telomerase-specific therapies is largely limited to the context of chemotherapy, despite reports of the beneficial effects of telomerase activation in the cardiovascular system in relation to such processes as endothelial dysfunction and myocardial infarction. Thus, there is a need for better understanding of telomerase-focused cell and organism physiology, as well as development of telomerase-specific therapies in relation to cancer and extension of these therapies to cardiovascular pathologies. This review will detail findings related to telomerase and evaluate its potential to serve as a therapeutic target. PMID- 27394170 TI - Chronic Inducible Urticaria (CIndU) versus Chronic Spontaneous Urticaria (CSU): Can new names and new updated information improve our care for patients with urticaria? PMID- 27394167 TI - A pyruvate decarboxylase-mediated therapeutic strategy for mimicking yeast metabolism in cancer cells. AB - Cancer cells have high rates of glycolysis and lactic acid fermentation in order to fuel accelerated rates of cell division (Warburg effect). Here, we present a strategy for merging cancer and yeast metabolism to remove pyruvate, a key intermediate of cancer cell metabolism, and produce the toxic compound acetaldehyde. This approach was achieved by administering the yeast enzyme pyruvate decarboxylase to triple negative breast cancer cells. To overcome the challenges of protein delivery, a nanoparticle-based system consisting of cationic lipids and porous silicon were employed to obtain efficient intracellular uptake. The results demonstrate that the enzyme therapy decreases cancer cell viability through production of acetaldehyde and reduction of lactic acid fermentation. PMID- 27394171 TI - Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment. AB - Waterpipe smoking and e-cigarette vaping, the non-combustible sources of inhaled nicotine exposure are increasingly becoming popular and marketed as safer alternative to cigarette smoking. Hence, this study was designed to investigate the impact of inhaled nicotine exposure on disease causing COPD-emphysema mechanisms. For in vitro studies, human bronchial epithelial cells (Beas2b) were treated with waterpipe smoke extract (WPSE, 5%), nicotine (5mM), and/or cysteamine (250MUM, an autophagy inducer and anti-oxidant drug), for 6hrs. We observed significantly (p<0.05) increased ubiquitinated protein-accumulation in the insoluble protein fractions of Beas2b cells treated with WPSE or nicotine that could be rescued by cysteamine treatment, suggesting aggresome-formation and autophagy-impairment. Moreover, our data also demonstrate that both WPSE and nicotine exposure significantly (p<0.05) elevates Ub-LC3beta co-localization to aggresome-bodies while inducing Ub-p62 co-expression/accumulation, verifying autophagy-impairment. We also found that WPSE and nicotine exposure impacts Beas2b cell viability by significantly (p<0.05) inducing cellular apoptosis/senescence via ROS-activation, as it could be controlled by cysteamine, which is known to have an anti-oxidant property. For murine studies, C57BL/6 mice were administered with inhaled nicotine (intranasal, 500MUg/mouse/day for 5 days), as an experimental model of non-combustible nicotine exposure. The inhaled nicotine exposure mediated oxidative-stress induces autophagy-impairment in the murine lungs as seen by significant (p<0.05, n=4) increase in the expression levels of nitrotyrosine protein-adduct (oxidative-stress marker, soluble fraction) and Ub/p62/VCP (impaired-autophagy marker, insoluble-fraction). Overall, our data shows that nicotine, a common component of WPS, e-cigarette vapor and cigarette smoke, induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment as a potential mechanism for COPD-emphysema pathogenesis. PMID- 27394172 TI - Extracellular superoxide dismutase is present in secretory vesicles of human neutrophils and released upon stimulation. AB - Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme present in the extracellular matrix (ECM), where it provides protection against oxidative degradation of matrix constituents including type I collagen and hyaluronan. The enzyme is known to associate with macrophages and polymorphonuclear leukocytes (neutrophils) and increasing evidence supports a role for EC-SOD in the development of an inflammatory response. Here we show that human EC-SOD is present at the cell surface of isolated neutrophils as well as stored within secretory vesicles. Interestingly, we find that EC-SOD mRNA is absent throughout neutrophil maturation indicating that the protein is synthesized by other cells and subsequently endocytosed by the neutrophil. When secretory vesicles were mobilized by neutrophil stimulation using formyl-methionyl-leucyl-phenylalanine (fMLF) or phorbol 12-myristate 13-acetate (PMA), the protein was released into the extracellular space and found to associate with DNA released from stimulated cells. The functional consequences were evaluated by the use of neutrophils isolated from wild-type and EC-SOD KO mice, and showed that EC-SOD release significantly reduce the level of superoxide in the extracellular space, but does not affect the capacity to generate neutrophil extracellular traps (NETs). Consequently, our data signifies that EC-SOD released from activated neutrophils affects the redox conditions of the extracellular space and may offer protection against highly reactive oxygen species such as hydroxyl radicals otherwise generated as a result of respiratory burst activity of activated neutrophils. PMID- 27394173 TI - 2-Oxoglutarate dehydrogenase is a more significant source of O2(.-)/H2O2 than pyruvate dehydrogenase in cardiac and liver tissue. AB - Pyruvate dehydrogenase (Pdh) and 2-oxoglutarate dehydrogenase (Ogdh) are vital for Krebs cycle metabolism and sources of reactive oxygen species (ROS). O2(. )/H2O2 formation by Pdh and Ogdh from porcine heart were compared when operating under forward or reverse electron transfer conditions. Comparisons were also conducted with liver and cardiac mitochondria. During reverse electron transfer (RET) from NADH, purified Ogdh generated ~3-3.5* more O2(.-)/H2O2 in comparison to Pdh when metabolizing 0.5-10uM NADH. Under forward electron transfer (FET) conditions Ogdh generated ~2-4* more O2(.-)/H2O2 than Pdh. In both liver and cardiac mitochondria, Ogdh displayed significantly higher rates of ROS formation when compared to Pdh. Ogdh was also a significant source of ROS in liver mitochondria metabolizing 50uM and 500uM pyruvate or succinate. Finally, we also observed that DTT directly stimulated O2(.-)/H2O2 formation by purified Pdh and Ogdh and in cardiac or liver mitochondria in the absence of substrates and cofactors. Taken together, Ogdh is a more potent source of ROS than Pdh in liver and cardiac tissue. Ogdh is also an important ROS generator regardless of whether pyruvate or succinate serve as the sole source of carbon. Our observations provide insight into the ROS generating capacity of either complex in cardiac and liver tissue. The evidence presented herein also indicates DTT, a reductant that is routinely added to biological samples, should be avoided when assessing mitochondrial O2(.-)/H2O2 production. PMID- 27394174 TI - Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ. AB - Spinocerebellar ataxia type 1 (SCA1), due to an unstable polyglutamine expansion within the ubiquitously expressed Ataxin-1 protein, leads to the premature degeneration of Purkinje cells (PCs), decreasing motor coordination and causing death within 10-15 years of diagnosis. Currently, there are no therapies available to slow down disease progression. As secondary cellular impairments contributing to SCA1 progression are poorly understood, here, we focused on identifying those processes by performing a PC specific proteome profiling of Sca1(154Q/2Q) mice at a symptomatic stage. Mass spectrometry analysis revealed prominent alterations in mitochondrial proteins. Immunohistochemical and serial block-face scanning electron microscopy analyses confirmed that PCs underwent age dependent alterations in mitochondrial morphology. Moreover, colorimetric assays demonstrated impairment of the electron transport chain complexes (ETC) and decrease in ATPase activity. Subsequently, we examined whether the mitochondria targeted antioxidant MitoQ could restore mitochondrial dysfunction and prevent SCA1-associated pathology in Sca1(154Q/2Q) mice. MitoQ treatment both presymptomatically and when symptoms were evident ameliorated mitochondrial morphology and restored the activities of the ETC complexes. Notably, MitoQ slowed down the appearance of SCA1-linked neuropathology such as lack of motor coordination as well as prevented oxidative stress-induced DNA damage and PC loss. Our work identifies a central role for mitochondria in PC degeneration in SCA1 and provides evidence for the supportive use of mitochondria-targeted therapeutics in slowing down disease progression. PMID- 27394175 TI - Pharmacokinetic profile of cefbuperazone in healthy Chinese volunteers after single and multiple drip intravenous infusion by HPLC-MS/MS. AB - A selective and reproducible HPLC-MS/MS method was developed and fully validated for the determination of cefbuperazone in human plasma and urine. Samples were prepared using protein precipitation and separated on a Zorbax Eclipse Plus C18 column (2.1*50mm, 3.5MUm). The API-4000 mass spectrometer was operated under multiple reaction monitoring mode (MRM) using the electrospray ionization technique. Linearity was achieved from 0.250 to 250MUg/mL in plasma and 20.0 5000MUg/mL in urine. The method was successfully applied to a pharmacokinetic study of cefbuperazone in healthy Chinese volunteers after drip intravenous infusion of 0.5, 1.0, 2.0g cefbuperazone sodium injection. Cefbuperazone reached a maximum concentration (Cmax) of 44.7+/-8.1MUg/mL, 86.7+/-12.7MUg/mL and 168+/ 14MUg/mL in 0.5, 1.0 and 2.0g dose groups respectively, at 60min after the start of infusion. The half-life (t1/2) was between 1.8-1.9h, and the elimination constant (kel) was between 0.36-0.39h(-1). The results proved that cefbuperazone showed linear pharmacokinetic profile in the dose range of 0.5-2.0g without gender difference. Drug accumulation was not observed. Cefbuperazone reached the maximum excretion rate in urine 2h after the start of infusion. About 60.0% of the administered drug was excreted via urine as unchanged form within 12h. The cumulative excretion of cefbuperazone after single drip intravenous infusion was proportional to the administered dose within the range from 0.5g to 2.0g. PMID- 27394176 TI - Metabolomic profile for the early detection of coronary artery disease by using UPLC-QTOF/MS. AB - Traditional risk factors cannot promote prediction capacity for the patients with coronary artery disease (CAD), who usually do not show apparent symptoms until they develop acute myocardial infarction (AMI). As such, novel predictive diagnostic strategies are essential to accurately define patients at risk of acute coronary syndrome. In this study, non-targeted metabolomic profiling using ultra-performance liquid chromatography coupled to time of flight mass spectrometry (UPLC-QTOF/MS) was performed in combination with multivariate statistical model to analyze the serum samples of patients with stable angina (n=38), acute myocardial infarction (AMI) (n=34) and healthy age- and gender matched controls (n=71). Results showed a clear distinction in metabolomic profiles between stable angina and AMI when using OPLS-DA with both positive and negative models. Internal cross-validation methods were used to confirm model validity with an area under the curve (AUROC)=0.983. We identified various classes of altered metabolites including phospholipids, fatty acids, sphingolipids, glycerolipids and steroids. We then demonstrated the differential roles of these metabolites using multivariate statistical model. Phospholipids previously associated with CAD were shown to have lower predictive capacity to discriminate AMI patients from stable angina patients. Interestingly, ceramides, bile acid and steroids hormone such as Cer(t18:0/16:0), Cer(d18:0/12:0), dehydroepiandrosterone sulfate (VIP scores of 1.99, 1.97, 1.64, respectively), were found to be associated with the progression of CAD. These results suggest that metabolomic approaches may facilitate the development of more stringent and predictive patient criteria in the diagnosis and treatment of CAD. PMID- 27394177 TI - Quantification of total content of non-esterified fatty acids bound to human serum albumin. AB - Non-esterified fatty acids bound to the human serum albumin (HSA) contribute to several HSAs properties of special concern in pathologies, for instance to the reactivity of the free HSA-Cys34 thiol group (important antioxidative thiol pool in plasma), and to the affinity for binding of molecules and ions (for example cobalt as a prominent biomarker in heart ischemia). Therefore, the method for determination of FAs bound to HSA was developed. FAs were released from HSA (previously isolated from serum by ammonium sulfate precipitation) using acidic copper(II) sulfate in phosphoric acid, extracted by n-heptane-chloroform (4:1, v/v) mixture, spotted on TL silica-gel and then developed with n-heptane chloroform-acetic acid (5:3:0.3, v/v/v). Common office flatbed scanner and software solution for densitometric image analysis, developed in R, were used. The linearity of calibration curve in concentration range from 0.1 to 5.0mmol/L stearic acid was achieved. The method was proved to be precise (with RSD of 1.4 4.7%) and accurate. Accuracy was examined by standard addition method (recoveries 97.2-102.5%) and by comparison to results of GC. The method is sample saving, technically less demanding, and cheap, and therefore suitable for determination of FAs/HSA ratio when elevated concentrations of free FAs are reliable diagnostic/risk parameter of pathological states. PMID- 27394178 TI - Impact of transfemoral versus transapical access on mortality among patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. AB - OBJECTIVE: To compare early and late mortality of transfemoral (TF) and transapical (TA) transcatheter aortic valve replacement (TAVR) patients and assess predictors for mortality. BACKGROUND: Studies have shown conflicting results regarding impact of access on outcome in severe aortic stenosis (AS) patients undergoing TAVR. METHODS: AS patients undergoing TAVR between May 2007 December 2014 were included. Baseline demographic, clinical, and imaging parameters were compared according to access, and landmark analysis models were generated to assess outcomes and associated factors. RESULTS: Among 648 severe AS patients undergoing TAVR, TF was used in 516 and TA in 132. Baseline characteristics between groups demonstrated lower body mass index, higher STS score, and rate of peripheral vascular disease among TA patients. Procedural complications were more common in the TA group, especially major bleeding (15% vs. 6%, p<0.001) and acute kidney injury >1 (8% vs. 1.4%, p<0.001). Landmark analysis demonstrated higher cumulative mortality rates at 30days among TA than TF patients (log-rank p<0.001), with similar mortality after 30days and up to 1 year (13% in both log-rank p=0.64). In a multivariate model, TA was an independent predictor of early mortality (HR=4.55 95% CI [12.5-1.6], p=0.003) along with pulmonary artery systolic pressure>60mmHg (HR=3.08 95% CI [7.37-1.29], p=0.01) and residual aortic regurgitation severity above mild (HR=3.99 95% CI [10.2-1.56], p=0.004). CONCLUSIONS: Patients undergoing TAVR via TA have higher adjusted early mortality and similar late mortality rates compared to TF, despite higher risk profile. PMID- 27394179 TI - Successful deployment of polytetrafluoroethylene-covered stent to seal left internal mammary artery graft perforation due to guide catheter extension system. AB - Coronary artery bypass graft perforation during percutaneous coronary intervention is a rare complication. Perforation of a left internal mammary artery (LIMA) graft due to a guide catheter extension system has not been described. We report the successful deployment of a polytetrafluoroethylene (PTFE)-covered stent to seal the LIMA graft perforation due to the guide catheter extension system. Percutaneous coronary intervention was performed for a culprit lesion of the distal left circumflex via the LIMA graft. A balloon catheter failed to be delivered because the LIMA graft was very long and tortuous. The guide catheter extension system was introduced, and the balloon was delivered and inflated. However, the LIMA graft perforation with continuous extravasation was caused by the edge of deeper intubated guide extension catheter when a coronary stent was attempted to be delivered to the culprit lesion. A long balloon inflation was performed, but the perforation was not completely sealed. The PTFE covered stent was successfully deployed and sealed the LIMA graft perforation. This case describes that the rapid deployment of PTFE-covered stent is effective to treat severe coronary artery bypass graft perforation due to the guide catheter extension system. PMID- 27394180 TI - Radial artery perforation treated with balloon tracking and guide catheter tamponade - A case series. AB - A 78year old woman was admitted with an acute coronary syndrome. She underwent coronary angiography via the left radial artery which was complicated by a guide catheter induced radial artery perforation confirmed by extravasation of contrast into the forearm. We used balloon assisted tracking and guide catheter tamponade to complete the angioplasty procedure via the radial artery and successfully seal the radial artery perforation. We describe a series of 7 cases where this technique was used to both treat radial artery perforation and to complete the angioplasty via the radial approach. PMID- 27394181 TI - Combined use of export catheter and penumbra vacuum thromboaspiration in a challenging case of acute common carotid artery occlusion. AB - A 76-year-old hypertensive man with previous bilateral iliac stenting was admitted in our center for acute stroke with an NIH score of 20 at 6 h from symptoms onset. The common carotid occlusion with a huge thrombus and a very calcified plaque has been successfully recanalyzed with a combination of coronary total occlusion technique, filter-aided coronary manual thrombectomy and Penumbra vacuum thrombectomy systems. PMID- 27394182 TI - Association between lipoprotein(a) and nonalcoholic fatty liver disease among Korean adults. AB - BACKGROUND: Lipoprotein(a) [Lp(a)] and nonalcoholic fatty liver disease (NAFLD) are risk factors for cardiovascular diseases. We investigated the relationship between Lp(a) concentrations and NAFLD among Korean adults. METHODS: A total of 2242 nondiabetic subjects undergoing routine health screening examination were enrolled. Anthropometric and biochemical parameters, including Lp(a) were measured. NAFLD were assessed by ultrasonography. Adjusted Odds ratios for the presence of NAFLD according to Lp(a) tertiles were estimated using logistic regression. RESULTS: Subjects were grouped according to the severity of NAFLD and Lp(a) concentrations. Lp(a) concentrations were decreased across the severity of NAFLD and the prevalence of NAFLD decreased with the Lp(a) tertiles. Compared with subjects in the lowest tertile of Lp(a), those in the highest tertile had higher total cholesterol and LDL-C concentrations and lower body mass index, blood pressure, fasting glucose, triglyceride, ALT, and HOMA-IR concentrations. In the logistic regression analysis after adjusting for multiple risk factors, the relationship between Lp(a) concentrations and the presence of NAFLD remained significant. However, this association was attenuated after adjusting for insulin resistance. CONCLUSIONS: Lp(a) was inversely associated with the presence of NAFLD, but it was not an independent risk factor for NAFLD among Korean adults. PMID- 27394183 TI - Arousal, Attention, and an Abundance of Opportunity to Advance Delirium Care. PMID- 27394184 TI - Transcriptome analysis of beer-spoiling Lactobacillus brevis BSO 464 during growth in degassed and gassed beer. AB - Lactobacillus brevis BSO 464 (Lb464) is a beer-spoilage-related (BSR) isolate of interest given its unique physiological attributes; specifically, it is highly hop-tolerant and exhibits very rapid growth in pressurized/gassed beer. RNA sequencing was performed on Lb464 grown in pressurized and non-pressurized beer to determine important genetic mechanisms for growth in these environments. The data generated were compared against data in a previous transcriptional study of another lactic acid bacterium (LAB) during growth in beer, namely, Pediococcus claussenii ATCC BAA-344(T) (Pc344). Results revealed that the most important genetic elements for Lb464 growth in beer are related to biogenic amine metabolism, membrane transport and fortification, nutrient scavenging, and efficient transcriptional regulation. Comparison with the previous transcriptional study of Pc344 indicated that the total coding capacity (plasmid profile and genome size) of a LAB isolate allows for beer-spoilage virulence and adaptation to different beer environments, i.e., the ability to grow in degassed beer (during production) or gassed beer (packaged product). Further, differences in gene expression of Lb464 and Pc344 during mid-exponential growth in beer may dictate how rapidly each isolate exhausts particular carbon sources during. The presence of headspace pressure/dissolved CO2 was found to drive Lb464 transcription during mid-exponential growth in beer towards increasing cell wall and membrane modification, transport, osmoregulation, and DNA metabolism and transposition events. This transcriptional activity resembles transcriptional patterns or signatures observed in a viable, but non-culturable state established by non-related organisms, suggesting that Lb464 overall uses complex cellular regulation to maintain cell division and growth in the stressful beer environment. Additionally, increased expression of several hypothetical proteins, the hop-tolerance gene horC, and DNA repair and recombination genes from plasmids pLb464-2, -4, and -8 were observed in the gassed beer environment. Thus, plasmids can harbor genes with specific (gassed) beer growth advantages, and confirm that plasmid transfer and acquisition as important activities for adaptation to the beer environment. PMID- 27394185 TI - N2 and P3 modulation during partial inhibition in a modified go/nogo task. AB - The neural response following the partial inhibition of responses can provide insight into the processes underlying response inhibition. We examined the N2 and P3 on trials where participants correctly responded to go stimuli, successfully inhibited their response to nogo stimuli, and nogo trials where they initiated but did not complete their response (partial inhibitions) in an adult sample (N=24, M(age)=21.17, SD(age)=3.52). An enhanced and delayed N2 was observed on partially inhibited compared to successfully inhibited nogo trials. Further analysis showed that this modulation was error-related. An enhanced central P3 was observed following successful inhibitions compared to correct go trials, but not following partial inhibitions. The results suggest that the central P3 enhancement is specific to the complete and successful inhibition of responses. Therefore, the absence of a central P3 on partial inhibitions could reflect insufficient inhibition or a monitored failure in inhibiting the response. Although, our findings provide support for the role of P3 in response inhibition, it raises questions about the processes involved in the subsequent inhibition or correction of the erroneous response. Further research examining the neural response following both partial and unsuccessful inhibitions could provide insight regarding these processes. PMID- 27394186 TI - The effects of ripasudil (K-115), a Rho kinase inhibitor, on activation of human conjunctival fibroblasts. AB - The most common cause of glaucoma surgery failure is scar formation induced by activation of wound-healing responses and resultant fibrosis at the surgical site. We investigated the effects of ripasudil, a Rho kinase inhibitor, on activation of human conjunctival fibroblasts (HConF). HConF were pretreated with different concentrations of ripasudil for 1 h before addition of transforming growth factor (TGF)-beta2, followed by incubation for 48 h. TGF-beta2-treated fibroblasts exhibited a significant increase in expression of alpha-smooth muscle actin (alpha-SMA), a marker of fibroblast-to-myofibroblast differentiation, and this increase was significantly suppressed, in a dose-dependent manner, by pretreatment with ripasudil. Ripasudil pretreatment also significantly attenuated TGF-beta2-induced fibronectin production and collagen gel contraction. TGF-beta2 increased both the number of viable cells and the number of cells in the G2/M phase of the cell cycle; these effects were attenuated by pretreatment with ripasudil. In addition, we explored the effects of ripasudil on stimulation of HConF by activated macrophages. Human monocytic cell line THP-1 cells were differentiated into M1 or M2 macrophage-like cells, and HConF were treated with conditioned media derived from these macrophages in the presence or absence of ripasudil. Conditioned medium from M2 macrophage-like cells induced a significant increase in alpha-SMA expression, viable cell numbers, and gel contraction, all of which were significantly suppressed by ripasudil. Thus, overall, ripasudil attenuated activation of human conjunctival fibroblasts. Ripasudil may be of therapeutic utility, preventing excessive scarring after glaucoma filtration surgery. PMID- 27394187 TI - Massive Cerebrospinal Fluid Replacement Reduces Delayed Cerebral Vasospasm After Embolization of Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND Delayed cerebral vasospasm (DCVS) following aneurismal subarachnoid hemorrhage (SAH) is a leading cause of poor prognosis and death in SAH patients. Effective management to reduce DCVS is needed. A prospective controlled trial was conducted to determine if massive cerebrospinal fluid (CSF) replacement (CR) could reduce DCVS occurrence and improve the clinical outcome after aneurysmal SAH treated with endovascular coiling. MATERIAL AND METHODS Patients treated with endovascular coiling after aneurysmal SAH were randomly divided into a control group receiving regular therapy alone (C group, n=42) and a CSF replacement group receiving an additional massive CSF replacement with saline (CR group, n=45). CSF examination, head CT, DCVS occurrence, cerebral infarction incidence, Glasgow Outcome Scale prognostic score, and 1-month mortality were recorded. RESULTS The occurrence of DCVS was 30.9% in the C group and 4.4% in the CR group (P<0.005). The cerebral infarction incidences in the C and CR groups were 19.0% and 2.2% (P<0.05), respectively, 1 month after the treatments. Mortality was not significantly different between the 2 groups during the follow-up period. CONCLUSIONS Massive CR after embolization surgery for aneurysmal SAH can significantly reduce DCVS occurrence and effectively improve the outcomes. PMID- 27394188 TI - Updated Clinical Practice Guidelines on Heart Failure: An International Alignment. PMID- 27394189 TI - 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. PMID- 27394190 TI - Quantitative proteomic profiling reveals hepatic lipogenesis and liver X receptor activation in the PANDER transgenic model. AB - PANcreatic-DERived factor (PANDER) is a member of a superfamily of FAM3 proteins modulating glycemic levels by metabolic regulation of the liver and pancreas. The precise PANDER-induced hepatic signaling mechanism is still being elucidated and has been very complex due to the pleiotropic nature of this novel hormone. Our PANDER transgenic (PANTG) mouse displays a selective hepatic insulin resistant (SHIR) phenotype whereby insulin signaling is blunted yet lipogenesis is increased, a phenomena observed in type 2 diabetes. To examine the complex PANDER induced mechanism of SHIR, we utilized quantitative mass spectrometry-based proteomic analysis using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) to reveal the global hepatic proteome differences within the PANTG under the metabolic states of fasting, fed and insulin-stimulated conditions. Proteomic analysis identified lipid metabolism as one of the top cellular functions differentially altered in all metabolic states. Differentially expressed proteins within the PANTG having a lipid metabolic role included ACC, ACLY, CD36, CYP7A1, FASN and SCD1. Central to the differentially expressed proteins involved in lipid metabolism was the predicted activation of the liver X receptor (LXR) pathway. Western analysis validated the increased hepatic expression of LXRalpha along with LXR-directed targets such as FASN and CYP7A1 within the PANTG liver. Furthermore, recombinant PANDER was capable of inducing LXR promoter activity in vitro as determined by luciferase reporter assays. Taken together, PANDER strongly impacts hepatic lipid metabolism across metabolic states and may induce a SHIR phenotype via the LXR pathway. PMID- 27394191 TI - Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial. AB - BACKGROUND: Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya. METHODS: We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)-Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0.5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks-4 months, 5-17 months), and by baseline CD4% (<10, 10-14, 15-19, and >=20). Data were obtained in an observer blind manner, and the vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01148459. FINDINGS: Between July 30, 2010, and May 24, 2013, we enrolled 200 children to our study and randomly assigned 99 to receive RTS,S/AS01 and 101 to receive rabies vaccine. 177 (89%) of the 200 children enrolled completed 14 months of follow-up. Serious adverse events were noted in 41 (41.4%, 95% CI 31.6-51.8) of 99 RTS,S/AS01 recipients and 37 (36.6%, 27.3-46.8) of 101 rabies-vaccine recipients (relative risk 1.1, 95% CI 0.8-1.6). 20 (20.2%, 95% CI 12.8-29.5) of 99 RTS,S/AS01 recipients and 12 (11.9%, 6.3-19.8) of 101 rabies vaccine recipients had at least one serious adverse event within 30 days after vaccination, mainly pneumonia, febrile convulsions, and salmonella sepsis. Five (5.1%, 95% CI 1.7-11.4) of 99 RTS,S/AS01 recipients and four (4.0%, 1.1-9.8) of 101 rabies-vaccine recipients died, but no deaths were deemed related to vaccination. Mortality was associated with five cases of pneumonia (1% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), five cases of gastroenteritis (3% RTS,S/AS01 recipients vs 2% rabies-vaccine recipients), five cases of malnutrition (2% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), one case of sepsis (1% rabies-vaccine recipients), one case of Haemophilus influenza meningitis (1% rabies-vaccine recipients), and one case of tuberculosis (1% RTS,S/AS01 recipients). INTERPRETATION: RTS, S/AS01 was well tolerated when given to children with WHO clinical stage 1 or 2 HIV disease along with high antiretroviral and co-trimoxazole use. Children with HIV disease could be included in future RTS,S/AS01 vaccination programmes. FUNDING: GlaxoSmithKline Biologicals SA and PATH Malaria Vaccine Initiative. PMID- 27394192 TI - A malaria vaccine in children with HIV. PMID- 27394193 TI - Web based health surveys: Using a Two Step Heckman model to examine their potential for population health analysis. AB - In June 2011 the BBC Lab UK carried out a web-based survey on the causes of mental distress. The 'Stress Test' was launched on 'All in the Mind' a BBC Radio 4 programme and the test's URL was publicised on radio and TV broadcasts, and made available via BBC web pages and social media. Given the large amount of data created, over 32,800 participants, with corresponding diagnosis, demographic and socioeconomic characteristics; the dataset are potentially an important source of data for population based research on depression and anxiety. However, as respondents self-selected to participate in the online survey, the survey may comprise a non-random sample. It may be only individuals that listen to BBC Radio 4 and/or use their website that participated in the survey. In this instance using the Stress Test data for wider population based research may create sample selection bias. Focusing on the depression component of the Stress Test, this paper presents an easy-to-use method, the Two Step Probit Selection Model, to detect and statistically correct selection bias in the Stress Test. Using a Two Step Probit Selection Model; this paper did not find a statistically significant selection on unobserved factors for participants of the Stress Test. That is, survey participants who accessed and completed an online survey are not systematically different from non-participants on the variables of substantive interest. PMID- 27394194 TI - Personality traits and body weight: Evidence using sibling comparisons. AB - RATIONALE: Past research has shown that personality traits relate to body weight, but this relationship may be confounded by unobserved family-level characteristics such as genetic endowments. OBJECTIVE: The purpose of this study was to investigate whether the association between personality traits, as measured by the Big Five taxonomy, and body weight among young adults is spurious owing to shared family background. METHODS: Participants were drawn from the full (n = 14,366) and family (n = 2813) samples of the National Longitudinal Study of Adolescent to Adult Health (Add Health). The study employed family-fixed effects to eliminate shared family background factors that might affect personality traits and body weight simultaneously. RESULTS: Among the Big Five personality traits, only conscientiousness showed a robust association with body weight, including body mass index (BMI) and obesity risk. These results were robust to adjustments for family-fixed effects, which indicates that the association between conscientiousness and body weight is generally not confounded by unobserved family-level characteristics shared by siblings. A one-standard deviation increase in conscientiousness was associated with a decrease in BMI by 0.89 (equivalent to a 2.5 kg decrease in weight for an individual with an average height of the sample) and a 12% reduction in the probability of being obese. This study also found some suggestive evidence of gender and racial/ethnic differences. The association between conscientiousness and obesity was larger and statistically significant only for women, and conscientiousness was most strongly associated with obesity among Hispanic people. CONCLUSION: Conscientiousness is associated with decreased body weight net of unobserved background characteristics that are shared by siblings. The results suggest that interventions that develop personality traits may have "spillover effects"; in other words, they may also help reduce obesity. PMID- 27394195 TI - Bacillus Calmette-Guerin vaccination at birth: Effects on infant growth. A randomized clinical trial. AB - BACKGROUND: Bacillus Calmette-Guerin vaccine (BCG) induces a complex, pro inflammatory immune response. Obesity is associated with low-grade inflammation. AIMS: The purpose of the study was to test whether BCG at birth has effects on infant growth and body composition. STUDY DESIGN, SUBJECTS, AND OUTCOME MEASURES: The Danish Calmette Study is a randomized, clinical trial. The study was conducted at three university hospitals and randomized 4262 children of gestational age >=32weeks to receive BCG within seven days of birth or to a no intervention control group. Follow-up consisted of clinical examinations. Outcome measures were weight and length at 3months, and weight, length, mid upper-arm circumference, and triceps and subscapular skinfold at 13months. Data collectors were blinded to allocation. Anthropometric measurements were converted to z scores using WHO reference population. RESULTS: Follow-up was 94% complete at 3 and 13months after birth. The children were bigger than the WHO reference population. There was no effect of BCG on weight z-score at 13months (-0.028 [95% confidence interval: -0.085 to 0.029], p=0.34). There was no effect on weight and length at 3months, or length, mid-upper-arm circumference, or triceps and subscapular skinfold at 13months. CONCLUSION: In this study, vaccination with BCG at birth did not have effects on child growth or body composition at 13months. TRIAL REGISTRATION: www.clinicaltrials.gov, registration number NCT01694108. PMID- 27394197 TI - Fanniidae (Insecta, Diptera) from Beijing, China, with key and description of one new species. AB - The Family Fanniidae in Beijing, China, consisting of seventeen species, is reviewed. Seven species represent new records from this region, including two species that are newly recorded from mainland China. One new species (Fannia papei sp. nov.) collected from the mountainous regions of Beijing is described. Three species (F. carbonaria, F. dupla and F. hirticeps) are re-described to provide updated characters and extensive variation information, and a key to identify the known males from Beijing is also given. PMID- 27394196 TI - Prediction of survival of diffuse large B-cell lymphoma patients via the expression of three inflammatory genes. AB - Currently, several gene-expression signatures that were used to predict survival of diffuse large B-cell lymphoma (DLBCL) patients, showed a restriction on the practical work for lack of convenient operation. In this study, we screened inflammatory genes whose expression correlated with survival of DLBCL and established a predictive model including IL6, IL1A and CSF3 through multivariate Cox regression based on the expression of these three genes. We validated the model at protein level in our clinical serum cohort composed of 101 patients of DLBCL and 50 healthy controls and 534 DLBCL patients at mRNA level from three independent Gene Expression Omnibus (GEO) data sets. We found our model to be independent of the International Prognostic Index (IPI), moreover, it can augment the predictive power of IPI. In summary, our three-gene model is sufficient to predict survival of DLBCL patients via measuring the concentration of three inflammatory cytokines in peripheral blood. PMID- 27394198 TI - The Cephenniini of China. VIII. New species and new records of Cephennodes Reitter of Hunan, Jiangxi, Zhejian and Fujian (Coleoptera: Staphylinidae: Scydmaeninae). AB - Seven new species of Cephennodes Reitter of mainland China are described, all in the nominotypical subgenus: C. brachyspinosus sp. n. (Hunan), C. impressibos sp. n. (Jiangxi), C. hystrix sp. n. (Zhejiang), C. setifer sp. n. (Zhejiang), C. yinziweii sp. n. (Zhejiang), C. datianpingensis sp. n. (Zhejiang), and C. bicribratus sp. n. (Zhejiang). Two species are placed in the Cephennodes bos species group (C. brachyspinosus and C. impressibos), three in the Cephennodes longipes group (C. hystrix, C. setifer and C. yinziweii), and two in a newly established Cephennodes elytratus group (C. datianpingensis and C. bicribratus). Additionally, three previously described species are recorded from new localities: C. capricornis Jaloszynski from Hunan and Zhejiang, C. clypeicornis Jaloszynski from Zhejiang and C. paramerus Jaloszynski from Fujian and Zhejiang. Cephennodes is for the first time reported to occur in Hunan Province. PMID- 27394199 TI - Cryptic species in the nuisance midge Polypedilum nubifer (Skuse (Diptera: Chironomidae) and the status of Tripedilum Kieffer. AB - Polypedilum nubifer (Skuse, 1889), originally described from Australia, is an apparently widespread species of Chironomidae (Diptera) that can attain nuisance densities in some eutrophic water bodies. Appropriate management depends upon the identity and ability to distinguish from potential cryptic taxa. A morphological study of larvae, pupae and adults of both sexes confirmed P. nubifer as widely distributed and frequently abundant, but also revealed two previously cryptic species of limited distribution in northern Australia. These species are described as new and illustrated in all stages here. Polypedilum quasinubifer Cranston sp. n. is described from north-west Queensland, Australia and also from Thailand and Singapore. Polypedilum paranubifer Cranston sp. n. is known only from retention ponds of a uranium mine in Northern Territory, Australia. Unusual morphological features of P. nubifer including alternate Lauterborn organs on the larval antenna, cephalic tubules on the pupa and frontal tubercles on the adult head are present in both new species as well. Newly slide-mounted types of Polypedilum pelostolum Kieffer, 1912 (lectotype designated here) confirm synonymy to Chironomus nubifer Skuse, 1889, examined also as newly-slide mounted types. Reviewed plus new evidence does not support recognition of Tripedilum Kieffer, 1921 as a separate taxon; therefore, Tripedilum is returned to junior synonymy with Polypedilum s. str. PMID- 27394200 TI - Review of the genus Diaphanogryllacris (Orthoptera: Gryllacrididae: Gryllacridinae) with description two new species from China. AB - Two new species of the genus Diaphanogryllacris from China are described, i.e. Diaphanogryllacris brevispina sp. nov. and Diaphanogryllacris incavatis sp. nov.. In addition, a distribution map of the species of the genus Diaphanogryllacris from China is presented. All material examined is deposited in the Museum of Hebei University. PMID- 27394201 TI - The Cretaceous Fossil Burmaculex antiquus Confirmed as the Earliest Known Lineage of Mosquitoes (Diptera: Culicidae). AB - A second female of mid-Cretaceous Burmaculex antiquus Borkent & Grimaldi, preserved in 99 myo Burmese amber, and the oldest known member of the Culicidae, is described in detail. Although generally opaque and distorted, some character states are added or refined. The discovery of well-developed scales on the legs shows that this feature must now be considered a synapomorphy of both the fossil and all extant members of the family. Previously described synapomorphies and further interpretation here confirm the phylogenetic position of this fossil as the sister group to extant and all known fossil Culicidae. It is placed in the new subfamily Burmaculicinae. PMID- 27394202 TI - Three new species of Calyptotheca (Bryozoa: Lanceoporidae) from the Great Barrier Reef, tropical Australia. AB - The cheilostome bryozoans Calyptotheca wulguru n. sp. and Calyptotheca tilbrooki n. sp. (Lanceoporidae) are described from inter-reefal, sediment-dominated habitats of the Great Barrier Reef, and Calyptotheca churro n. sp. was washed up on a Heron Island beach, with uncertain origin. Calyptotheca wulguru n. sp. and C. churro n. sp. belong to a subgroup of Calyptotheca species with numerous small, oval, marginal adventitious avicularia and suboral nodular thickening or umbones. The vicarious avicularia of C. tilbrooki n. sp. are elongate-oval, unlike those of other known Calyptotheca species, and C. tilbrooki n. sp. has more pronounced orificial dimorphism than in any other known Calyptotheca species. Calyptotheca churro n. sp. has the most pronounced suboral umbo of all known Calyptotheca species. This study increases the known Calyptotheca species of the Great Barrier Reef to ten, and of tropical Australia to 14. PMID- 27394203 TI - A new species of sand crab Jonas Hombron & Jacquinot, 1846 (Crustacea:
Decapoda: Brachyura: Corystidae) from the southeastern coast of India. AB - A new species of sand crab of the genus Jonas Hombron & Jacquinot, 1846 (family Corystidae) is described from specimens collected from Kalpakkam, southeastern coast of India. Two other species, J. indicus (Chopra, 1935), and J. choprai Serene, 1971, have previously been recorded from this area. A detailed description of the new species is given and compared with the closely related J. formosae Balss, 1922, also from the Indo-West Pacific. PMID- 27394204 TI - Description of two new species of Nelphe Herrich-Schaffer, with comments on the genus (Lepidoptera, Erebidae, Arctiinae, Arctiini, Ctenuchina). AB - Two new species of Ctenuchina are described from Haiti and Dominica, respectively: Nelphe trimaculata Pinheiro, sp. nov., and N. dominica Pinheiro, sp. nov. Nelphe trimaculata differs from all other species of Nelphe in the three linear (as opposed to round) dark brown markings on cell CuP-1A and on the inner margin of the forewings. Nelphe dominica differs from other species placed in Nelphe in the sixth and seventh abdominal tergites, with orange scales covering not only the lateral surfaces of the tergites as it occurs in other species, but also the dorsal surface. Both new taxa are illustrated in habitus and genitalia, and comments on the genus, now with 13 valid species, are provided. PMID- 27394205 TI - Description of Heliocypha vantoli spec. nov. from Siberut in the Mentawai Islands (Odonata: Chlorocyphidae). AB - Heliocypha vantoli Hamalainen, spec. nov. [holotype ? from Indonesia, Mentawai Islands (off Sumatra), Siberut Island, 29-31 January 2013, deposited at RMNH, Leiden, The Netherlands] is described and illustrated for both sexes and compared with the Heliocypha species found in Sumatra and adjacent small islands. Notes on the Odonata fauna of the Mentawai Islands are also provided. Euphaea aspasia Selys, 1853 (Euphaeidae) is recorded as new to these islands; differences in the colour pattern of the Siberut and mainland Sumatran specimens are briefly discussed. PMID- 27394206 TI - A revision of the genus Leberis Smirnov, 1989 (Cladocera: Chydoridae) in the Old World and Australia. AB - A comparison between populations of the diaphanus-group of Leberis Smirnov, 1989 from Australia and India confirmed that Australian L. diaphanus (King, 1853) and Indian L. punctatus (Daday, 1898) are separate species. Morphology of parthenogenetic females of L. punctatus is redescribed for the first time. Some fine details of morphology are re-examined in other species of Leberis, taxonomically significant features and their variability are studied. In the Old World L. punctatus could be confused with L. diaphanus, but the former differs from the latter mainly in the details of thoracic limbs I and IV. Both species have relatively broad distribution ranges: L. punctatus inhabits South Asia, Africa and penetrates Southeast Asia, L. diaphanus is a widespread taxon in the water bodies of Australia, Southeast Asia and South China. Diversity of the genus in the Old World is underestimated yet, and further investigations are desirable. PMID- 27394207 TI - Exploring the utility of DNA barcoding in species delimitation of Polypedilum (Tripodura) non-biting midges (Diptera: Chironomidae). AB - In this study, we tested the utility of the mitochondrial gene cytochrome c oxidase subunit 1 (CO1) as the barcode region to deal with taxonomical problems of Polypedilum (Tripodura) non-biting midges (Diptera: Chironomidae). The 114 DNA barcodes representing 27 morphospecies are divided into 33 well separated clusters based on both Neighbor Joining and Maximum Likelihood methods. DNA barcodes revealed an 82% success rate in matching with morphospecies. The selected DNA barcode data support 37-64 operational taxonomic units (OTUs) based on the methods of Automatic Barcode Gap Discovery (ABGD) and Poisson Tree Process (PTP). Furthermore, a priori species based on consistent phenotypic variations were attested by molecular analysis, and a taxonomical misidentification of barcode sequences from GenBank was found. We could not observe a distinct barcode gap but an overlap ranged from 9-12%. Our results supported DNA barcoding as an ideal method to detect cryptic species, delimit sibling species, and associate different life stages in non-biting midges. PMID- 27394208 TI - Biting midges of the tribe Ceratopogonini (Diptera: Ceratopogonidae) from the Middle East, with keys and descriptions of new species. AB - Middle East predatory biting midges of the tribe Ceratopogonini, covering 22 species of 7 genera are reviewed. Three new species are described and illustrated: Allohelea israelensis Szadziewski & Alwin sp. nov., Kolenohelea levantica Szadziewski & Alwin sp. nov. and Serromyia galilaeae Szadziewski & Alwin sp. nov. The genus Boreohelea Clastrier & Delecolle, 1990 syn. nov. is recognized as a junior synonym of Allohelea Kieffer, 1917. Thysanognathus nilogenes Kieffer, 1925 syn. nov. from Egypt is a junior synonym of Alluaudomyia melanosticta (Ingram & Macfie, 1922). Keys to identification of subfamilies, tribes, genera and species of Ceratopogonini of the Middle East are also provided. PMID- 27394209 TI - Two species of Nilothauma Kieffer (Diptera, Chironomidae) from Japan, with description of a new species. AB - The male and female adults and pupa of Nilothauma niidaense n. sp. are described and illustrated on the basis of the material collected from a fontal stream in Fukushima Prefecture, Japan. N. sasai Adam & Saether is treated as a junior synonym of N. hibaratertium Sasa, of which the male is redescribed. The Adam & Saether key to Nilothauma males is revised. PMID- 27394210 TI - Description of a new species of Tomiyamichthys from Australia with a discussion of the generic name. AB - Tomiyamichthys levisquama is described as a new species from the Northern Territory and Queensland, Australia from estuaries and soft bottom marine environments. It is distinctive in body and head shape, head coloration and by the absence of ctenoid scales on the body. It is compared with the related species Tomiyamichthys russus (Cantor 1849), which has ctenoid scales on the posterior part of the body. The validity of the name Tomiyamichthys over Flabelligobius is discussed, with both genera being described in the same paper, here accepting Tomiyamichthys as the appropriate name. PMID- 27394211 TI - Antillonatus, a new replacement name for the generic homonym Antillopsyche Nunez & Davis, 2016 (Lepidoptera: Tineoidea: Psychidae). AB - We have been informed that the name Antillopsyche Nunez & Davis 2016, type species Antillopsyche sessilis Nunez & Davis, 2016, which we recently proposed for a new genus of bagworm moths (Nunez & Davis 2016), is preoccupied by Antillopsyche Banks, 1941. This senior name was published for a genus of Trichoptera in the family Polycentropodidae (Banks 1941). We therefore propose the new name Antillonatus Nunez & Davis to replace the junior homonym Antillopsyche Nunez & Davis. The new generic name is derived from Antillae, the Latin word for Antilles, the archipelago where this taxon occurs, and the Latin natus (be born/begotten/arisen) in reference to the West Indian origin of the type species, which is the only known member of the genus. PMID- 27394212 TI - Euconnus franzi Asenjo, new name on Neotropical Euconnus Thomson (Coleoptera: Staphylinidae: Scydmaeninae: Glandulariini). AB - During my doctoral studies, while assembling a taxonomic list of the Staphylindae of Brazil (Asenjo et al. 2013: 229), I found a primary junior homonym in the genus Euconnus Thomson. The purpose of this note is to provide a correction to this problem. PMID- 27394213 TI - A new addition to the subfamily Anabropsinae (Orthoptera: Anostostomatidae) from China. AB - The paper describes one very interesting genus and species, Brevipenna Shi & Bian gen. nov. and B. falcata Shi & Bian sp. nov.. The genus shares similar characters with macropterous genus Pteranabropsis Gorochov, 1988 and apterous or subapterous genus Apteranabropsis Gorochov, 1988 in following: distributed in Asia, presence both tympana, male ninth abdominal tergite with 1 pair of lobes, which continue with the paired hooks of tenth abdominal tergite, and paraproct specialized with 2 long sclerotized processes. The tegmina and hind wings are short, and right and left ones overlapped. Therefore, we conclude the new genus may be intermediate state between the Pteranabropsis and Apteranabropsis. Perhaps, future study will suggest the three genera be combined. All the material is deposited in the Museum of Hebei University. PMID- 27394214 TI - A revision of Japanese Epuraeinae (Coleoptera, Nitidulidae). Part I. Epuraea subgenera: Dadopora Thomson, Epuraea Erichson, and Epuraeanella Crotch. AB - Three subgenera of Epuraea: Dadopora Thomson, Epuraea Erichson, and Epuraeanella Crotch, are revised for Japan. Thirty-six species are recognized. The following six are new records for Japan: Epuraea (Epuraea) laferi Kirejtshuk; E. (E.) melina Erichson; E. (E.) pygmaea (Gyllenhal); E. (E.) quadrangula Motschulsky; E. (E.) reichardti Sjoberg; and E. (Dadopora) vicaria Kirejtshuk & Kvamme. The following species are synonymized: E. (E.) hisamatsui Nakane with E. (E.) rufomarginata (Stephens) syn. nov.; and E. (E.) alpicola Nakane with E. (E.) terminalis (Mannerheim) syn. nov. The following two species are removed from the Japanese fauna: E. (Dadopora) fuscicollis (Stephens) and E. (E.) longula Erichson; the former was erroneously recorded as E. fuscicollis (Stephens, 1835) by Kashizaki & Hisamatsu (2011), and the latter is corrected as E. (E.) pseudorapax Kirejtshuk. The following three species are described as new: E. (E.) apiciclara sp. nov.; E. (E.) camura sp. nov.; and E. (E.) foramina sp. nov. Dorsal habitus, antenna, protibia, male and female genitalia, internal sac sclerites of male genitalia, and other important diagnostic characters of all species are illustrated. Keys are presented to Epuraeinae tribes, genera, subgenera, and Epuraea species of in the following subgenera: Dadopora, Epuraea, and Epuraeanella. PMID- 27394215 TI - Revision of the Palaearctic species of Eupelmus (Eupelmus) Dalman (Hymenoptera: Chalcidoidea: Eupelmidae). AB - One hundred-four extant species of Eupelmus Dalman (Hymenoptera: Eupelmidae: Eupelminae) are recognized from the Palaearctic region, of which 76 species of E. (Eupelmus) are recognized following a revision of the Palaearctic fauna of the subgenus. The following 25 species are described as new: E. (Eupelmus) adustus Gibson & Fusu n. sp., E. (Eupelmus) angustifrons Gibson & Fusu n. sp., E. (Eupelmus) bicolor Gibson & Fusu n. sp., E. (Eupelmus) brachypterus Fusu & Gibson n. sp., E. (Eupelmus) brachystylus Gibson & Fusu n. sp., E. (Eupelmus) brachyurus Fusu & Gibson n. sp., E. (Eupelmus) fasciatus Gibson & Fusu n. sp., E. (Eupelmus) gelechiphagus Gibson & Fusu n. sp., E. (Eupelmus) hayei Gibson & Fusu n. sp., E. (Eupelmus) infimbriatus Gibson & Fusu n. sp., E. (Eupelmus) iris Fusu & Gibson n. sp., E. (Eupelmus) kamijoi Gibson & Fusu n. sp., E. (Eupelmus) lanceolatus Gibson & Fusu n. sp., E. (Eupelmus) luteipes Fusu & Gibson n. sp., E. (Eupelmus) magdalenae Fusu & Gibson n. sp., E. (Eupelmus) mehrnejadi Gibson & Fusu n. sp., E. (Eupelmus) melanostylus Gibson & Fusu n. sp., E. (Eupelmus) punctatifrons Fusu & Gibson n. sp., E. (Eupelmus) setosus Fusu & Gibson n. sp., E. (Eupelmus) tanystylus Gibson & Fusu n. sp., E. (Eupelmus) tetrazostus Gibson & Fusu n. sp., E. (Eupelmus) vanharteni Fusu & Gibson n. sp., E. (Eupelmus) weilli Fusu & Gibson n. sp., E. (Eupelmus) xenium Fusu & Gibson n. sp., and E. (Eupelmus) zebra Fusu & Gibson n. sp. Of previously described species of Eupelmus, 17 are newly assigned to E. (Eupelmus), 10 to E. (Episolindelia Girault), and 8 to E. (Macroneura Walker). Formally transferred to E. (Macroneura) from Macroneura are E. (M.) algiricus (Kalina 1981), E. (M.) coleophorae (Kalina 1981), E. (M.) impennis (Nikol'skaya 1952), E. (M.) longicornis (Kalina 1981), E. (M.) pleuratus (Kalina 1981) and E. (M.) sugonyaevi (Kalina 1981) n. combs. Eupelmus (Eupelmus) kalinai Gibson & Fusu n. name is given to replace E. (Eupelmus) algiricus Kalina 1988, a secondary homonym of E. (M.) algiricus (Kalina 1981). New synonyms proposed are Eupelmus scolyti Liao 1987 n. syn. under E. (Eupelmus) formosae Ashmead 1904, and Eupelmus nigricauda Nikol'skaya 1952 n. syn. under E. (Eupelmus) microzonus Forster 1860. Eupelmus gueneei Giraud 1870 and Eupelmus xambeui Giard 1900 are transferred to Arachnophaga (Parasolindenia Brues) as A. (P.) gueneei (Giraud) and A. (P.) xambeui (Giard) n. combs., and Eupelmus kim Nikol'skaya 1952 is transferred to Brasema Cameron as B. kim (Nikol'skaya) n. comb. Eupelmus puparum Newport 1840 is transferred to Pteromalus Swederus (Pteromalidae) as P. puparum (Newport) n. comb., a secondary homonym of P. puparum (Linnaeus 1758), and Ceraphron brachynterae Schwagrichen 1835 is removed from Eupelmus and Eupelmidae, and the name treated as incertae sedis. Lectotypes are designated for Eupelmus azureus Ratzeburg 1844, Pteromalus cordairii Ratzeburg 1844, Eupelmus hostilis Forster 1860, and Eupelmus splendens Giraud 1872. Neotypes are designated for Pteromalus audouinii Ratzeburg 1844 and Eupelmus bedeguaris Ratzeburg 1852. Newly recorded from the Palaearctic are E. (Eupelmus) orthopterae (Risbec 1951) and E. (Eupelmus) peculiaris Narendran (2011). Excluded from the Palaearctic are E. (Eupelmus) afer Silvestri 1914 (Afrotropical) and E. (Eupelmus) longicorpus (Girault 1915) (Australasian), the former being compared to E. confusus Al khatib 2015 and the latter to E. iranicus Kalina 1988 and E. kalinai. Seven informal species groups are recognized for the purpose of species comparisons, the fulgens , fulvipes-, iranicus-, orientalis-, splendens-, stramineipes-, and urozonus groups. The latter group is restricted to E. urozonus Dalman and five other species that were differentiated initially using molecular evidence. Females of all 76 species of E. (Eupelmus) recognized from the Palaearctic are keyed, described and illustrated. Males are recognized for 44 of the species, and keyed and illustrated, though not all males of the fulvipes- and urozonus-groups are distinguished from each other. PMID- 27394216 TI - Revision of Platycheirus Lepeletier and Serville (Diptera: Syrphidae) in the Nearctic north of Mexico. AB - The 75 Nearctic species of Platycheirus Lepeletier and Serville found north of Mexico are revised, including five species new to North America: Platycheirus alpigenus Barkalov and Nielsen, Platycheirus brunnifrons Nielsen, Platycheirus clausseni Nielsen, Platycheirus speighti Doczkal, Stuke & Goeldlin, and Platycheirus splendidus Rotheray. Platycheirus rufimaculatus Vockeroth, Melanostoma willistoni Goot, and Melanostoma concinnus Snow are recognized as junior synonyms of Platycheirus pictipes (Bigot). Melanostoma carinata Curran is recognized as a junior synonym of Platycheirus chilosia (Curran). Melanostoma atra Curran is recognized as a junior synonym of Platycheirus luteipennis (Curran). Platycheirus holarcticus Vockeroth is recognized as a junior synonym of Syrphus naso Walker. Platycheirus trichopus (Thomson) is resurrected and represents what was previously considered the western population of Platycheirus obscurus (Say). One new species, Platycheirus neoperpallidus Young sp. nov., is described. Females of 26 species are described for the first time, and an illustrated key to Nearctic Platycheirus is presented. DNA barcode data are presented for 60 Nearctic species and a COI gene tree of all available world Platycheirus species, as well as morphological and combined morphological/COI phylogenetic analyses of the Platycheirus albimanus species group are presented and discussed. PMID- 27394217 TI - The Brachodidae of Sub-Saharan Africa (Lepidoptera, Cossoidea), with implications for the origin of the family. AB - Brachodidae are a small family of day-flying, rarely collected cossoid moths. Here, the Brachodidae fauna of Sub-Saharan Africa and the neighboring Arabian Peninsula is reviewed with special attention to the species of the subfamily Brachodinae. The origin of the African Brachodinae and their relationship to the Palaearctic genus Brachodes are discussed, and a Gondwanan origin of the family Brachodidae sensu stricto is proposed. A total of 34 brachodid species are considered in this study, most of which are figured. Two new genera, Archaeotychia gen. nov. (type species Atychia quiris Felder & Rogenhofer, 1875) and Nothobrachodes gen. nov. (type species Atychia infanda Meyrick, 1920) are described. Furthermore, 12 species are described as new to science: Archaeotychia semicuprea sp. nov., Archaeotychia dicksoni sp. nov., Archaeotychia khoisanorum sp. nov., Archaeotychia krooni sp. nov., Archaeotychia dentata sp. nov., Phycodes nigeriana sp. nov., Nigilgia scoblei sp. nov., Nigilgia agassizi sp. nov., Nigilgia ruwenzoriensis sp. nov., Nigilgia megabella sp. nov., Nigilgia arcana sp. nov. and Nigilgia crocea sp. nov. Moreover, Atychia metaspila Meyrick, 1926 syn. nov. is established as a new synonym of Archaeotychia albiciliata (Walsingham, 1891), and Atychia nycteropis Meyrick, 1920 syn. nov. as a new synonym of Nothobrachodes infanda (Meyrick, 1920). Atractoceros xanthoprocta (Meyrick, 1914) is transferred to the subfamily Phycodinae. PMID- 27394218 TI - A new species of flea-toad (Anura: Brachycephalidae) from southern Atlantic Forest, Brazil. AB - We describe a new species of Brachycephalus that is morphologically similar to the flea-toads B. didactylus, B. hermogenesi, and B. pulex. The new species occurs from the sea level up to 1000 m and it is widely distributed throughout southern Atlantic Forest. Brachycephalus sulfuratus sp. nov. is distinguished from all of its congeners by the combination of the following characters: (1) small body size (SVL of adults: 7.4-8.5 mm for males and 9.0-10.8 mm for females); (2) "leptodactyliform" body; (3) pectoral girdle arciferal and less robust compared to the Brachycephalus species with "bufoniform" body; (4) procoracoid and epicoracoid fused with coracoid but separated from the clavicle by a large fenestrae; (5) toe I externally absent; toes II, III, IV, and V distinct; phalanges of toes II and V reduced; (6) skin smooth with no dermal ossifications; (7) in life, general background color brown with small dark-brown spots; skin of throat, chest, arms, and forearms with irregular yellow blotches; in ventral view, cloacal region of alive and preserved specimens surrounded by a dark-brown inverted v-shaped mark outlined with white; (8) advertisement call long, composed of a set of 4-7 high-frequency notes (6.2-7.2 kHz) repeated regularly. PMID- 27394219 TI - Species diversity of fiddler crabs, genus Uca Leach, 1814 (Crustacea: Ocypodidae), from Taiwan and adjacent islands, with notes on the Japanese species. AB - The fiddler crabs, genus Uca Leach, 1814 (Decapoda, Ocypodidae) of Taiwan, including the offshore islands of Penghu (Pescadores), Kinmen (Quemoy), Matsu (Matzu), and Dongsha (Pratas), are revised, with the recognition of five subgenera and 15 species, viz. Uca (Austruca) Bott, 1973: U. lactea (De Haan, 1835), U. perplexa (H. Milne Edwards, 1837), U. triangularis (A. Milne-Edwards, 1873); U. (Gelasimus) Latreille, 1817: U. borealis Crane, 1975, U. jocelynae Shih, Naruse & Ng, 2010, U. tetragonon (Herbst, 1790), U. vocans (Linnaeus, 1758); U. (Paraleptuca) Bott, 1973: U. crassipes (White, 1847), U. splendida (Stimpson, 1858); U. (Tubuca) Bott, 1973: U. acuta (Stimpson 1858), U. arcuata (De Haan, 1835), U. coarctata (H. Milne Edwards, 1852), U. dussumieri (H. Milne Edwards, 1852), U. paradussumieri (Bott, 1973); and U. (Xeruca) Shih, 2015: U. formosensis Rathbun, 1921. Among them, U. acuta, U. paradussumieri, and U. vocans are confirmed to be distributed in Taiwan. Uca formosensis is endemic to Taiwan. The Uca species of the main islands of Japan are also listed. Four species (U. arcuata, U. lactea, U. crassipes and U. borealis) are known, but the recent additional records of U. perplexa and U. vocans need further confirmation. Except U. acuta, U. borealis, U. formosensis, U. lactea, and U. paradussumieri, other 10 Taiwanese species can be found from the Ryukyus too. Only one endemic species, U. boninensis, is reported from the Ogasawara (Bonin) Islands. A key to the 18 species of Uca found in East Asia is also provided in this study. PMID- 27394220 TI - Revision of the shore-fly genus Peltopsilopa Hendel (Diptera: Ephydridae). AB - The Neotropical shore-fly genus Peltopsilopa Hendel is revised and now includes three species: P. acuta n.sp.; P. anisotomoides (Karsch), new combination; and P. schwarzi Cresson. A fourth species name, P. aspistes Hendel, is recognized as a junior synonym of P. anisotomoides (Karsch). We confirm that Peltopsilopa is closely related to Cressonomyia Arnaud and that the genus is in the tribe Psilopini, subfamily Discomyzinae. We provide a revised generic diagnosis and key to South American genera of Psilopini to facilitate identification of Peltopsilopa. The included species descriptions are extensively documented with illustrations, photographs, and distribution map. PMID- 27394221 TI - Description of the final instar larva of Orthetrum borneense Kimmins, 1936 (Odonata, Libellulidae), using rearing and molecular methods. AB - The final instar larva of Orthetrum borneense Kimmins, 1936, is described and figured for the first time based on exuviae from three male and six female larvae collected in Sarawak, Borneo (East Malaysia). It is compared with an early instar larva, which was matched to the adult O. borneense by DNA barcoding, and the known larvae of other species of this genus that occur in the region. PMID- 27394223 TI - Capoeta anamisensis, a new species from the Minab and Hasan Langhi River drainages in Iran (Teleostei: Cyprinidae). AB - Capoeta anamisensis, from the Minab and Hasal Langhi River drainages in southern Iran, belongs to the C. trutta species group. Capoeta anamisensis is distinguished from other species of the C. trutta species group by the combination of the following characters: flank silvery without black spots; 56-67 scales in total along the lateral series; 11-12 scales above the lateral line and 21-25 gill rakers. Capoeta anamisensis is also distinguished from all other congeners in the Persian Gulf basin by having four fixed, diagnostic nucleotide substitutions in the mtDNA COI barcode region and five fixed, diagnostic nucleotide substitutions in the mtDNA cyt b region. The type of Capoeta barroisi persica is identified as an aberrant individual of C. trutta and is considered as a synonym of that species. PMID- 27394222 TI - Pareuchiloglanis hupingshanensis, a new species of the glyptosternine catfish (Siluriformes: Sisoridae) from the middle Yangtze River, China. AB - A new glyptosterniod catfish, Pareuchiloglanis hupingshanensis, is described on the basis of 29 specimens, which were collected from Hunan Hupingshan National Nature Reserve (HHNNR) in the Yangtze River basin, China. It can be distinguished from all congeners by morphology and sequences of the cytochrome b gene. Morphometric and molecular data show that the new species is closely related to P. sinensis Hora et Silas but differs from it in possessing a premaxillary tooth band with a deeper median indentation; a dentary tooth band which consists of two shorter and wider patches; a lower angle of gill opening, opposite to the base of the 4th or 5th (vs. second or third) branched pectoral-fin ray; an upper lip edged with dense papillae; the posterior end of the ventral fin falling distinctly short of (vs. almost reaching ) anus; a shorter dorsal fin; and a greater caudal-fin base depth. PMID- 27394224 TI - A review of the genus Entisberus Distant (Hemiptera: Heteroptera: Rhyparochromidae: Drymini). AB - The genus Entisberus Distant is reviewed and illustrated and diagnostic characters listed. The type species, E. archetypus Distant is illustrated and diagnostic characteristics noted. The female of E. bergrothi Kondorosy is described for the first time. A new species, E. interruptus from Mindanao [Island] in the Republic of the Philippines, is described, and a revised key to the species of Entisberus is given. PMID- 27394225 TI - Review of the genus Saprinus Erichson, 1834 from Madagascar and adjacent islands with description of a new species (Coleoptera: Histeridae: Saprininae) Third contribution to the knowledge of the Histeridae of Madagascar. AB - Clown beetles belonging to the genus Saprinus Erichson, 1834 from Madagascar and adjacent islands are reviewed. The Malagasy fauna of Saprinus consists of seven species: Saprinus (Saprinus) erichsonii Marseul, 1855; Saprinus (Saprinus) fulgidicollis Marseul, 1855; Saprinus (Saprinus) basalis Fairmaire, 1898; Saprinus (Saprinus) cupreus Erichson, 1834; Saprinus (Saprinus) chalcites (Illiger, 1807); Saprinus (Saprinus) splendens (Paykull, 1811); one species S. (Saprinus) labordei sp. nov., is described as new. Saprinus erichsonii Marseul, 1855 is transferred from the subgenus Phaonius Reichardt, 1941 into the nominotypical subgenus based on the morphological evidence. Lectotypes of the following species are designated: Saprinus erichsonii Marseul, 1855; Saprinus basalis Fairmaire, 1898 and Saprinus fulgidicollis Marseul, 1855. Saprinus (Saprinus) cupreus Erichson, 1834 is newly reported from Madagascar and Saprinus (Saprinus) basalis Fairmaire, 1898 is newly reported from the following countries: Congo, Gambia, Central African Republic, Namibia, Zimbabwe and Republic of South Africa. PMID- 27394227 TI - Revision of Calobrachium Gobbi & Azevedo, gen. nov. (Hymenoptera,
Bethylidae), with description of seven new Oriental species. AB - A new genus, Calobrachium Gobbi & Azevedo, gen. nov. (type species Calobrachium salum Gobbi & Azevedo, sp. nov.) with seven new species, C. luangum sp. nov., C. miticum sp. nov., C. pongum sp. nov., C. salum sp. nov., C. thanum sp. nov., C. trilinum sp. nov., C. vancum sp. nov. are described and figured. New combination is proposed for C. lepidum (Terayama, 2004), comb. nov. (from Pseudisobrachium Kieffer). A key to species of the genus based on males is given. PMID- 27394226 TI - Revision of the Oriental genus Holophris Mocsary, 1890 and description of the genus Leptopareia Rosa & Xu, gen. nov. (Hymenoptera, Chrysididae). AB - Two Oriental genera of the tribe Elampini (Chrysidinae) are here discussed. The genus Holophris Mocsary, 1890 is redescribed, and the genus Leptopareia Rosa & Xu, gen. nov. (type species Hedychrum borneanum Cameron, 1908) is established. Two new species are described: Holophris thailandica Rosa, Wei, Notton & Xu, sp. nov. (Thailand), and Leptopareia luzonensis Rosa, Wei, Notton & Xu, sp. nov. (Philippines, Luzon). The lectotype of Hedychrum borneanum Cameron, 1908 is designated. New combinations are proposed for L. borneana (Cameron, 1908), comb. nov., L. purpurea (Smith, 1860), comb. nov., L. abyssinica (Mocsary, 1914), comb. nov., L. confusa (Kimsey, 1988), comb. nov., L. congoensis (du Buysson, 1900), comb. nov., and L. kalliopsis (Zimmermann, 1961), comb. nov. (all are from Holophris Mocsary). Holophris marginella (Mocsary, 1890) is newly recorded from China and Thailand; H. taiwana (Tsuneki, 1970) from India, Indonesia and Laos; and Leptopareia borneana (Cameron, 1908) from Thailand. Keys to Oriental genera of the tribe Elampini and to Oriental species of the two genera are provided. PMID- 27394228 TI - Molecular analysis of the Pygospio elegans group of species (Annelida: Spionidae). AB - Pygospio elegans Claparede, 1863, the type species of the genus Pygospio, was originally described from Normandy, France, and later widely reported from boreal waters in the northern hemisphere. Sequence data of four gene fragments (2576 bp in total) of the mitochondrial 16S rDNA, nuclear 18S and 28S rDNA, and Histone 3 have shown that individuals from California and Oregon, USA, Scotland and the White Sea, Russia were genetically similar (the average p-distances for the combined data between the four groups ranged from 0.04 to 0.16%, average p = 0.1%). These individuals are considered to be conspecific and the amphiboreal distribution of P. elegans is here confirmed. Adult morphology of the species is briefly described and illustrated. The molecular analysis revealed two genetically distant populations, Pygospio sp. 1 from the Sea of Okhotsk and Pygospio sp. 2 from Oregon. The morphological differences and high average genetic p-distances for the combined data (ranging from 3.06 to 3.18%, average p = 3.12%) between Pygospio sp. 2 and P. elegans suggest the presence of an undescribed Pygospio species co-occurring with P. elegans in Oregon. High morphological similarity and moderate genetic p-distances for the combined data (ranging from 1 to 1.11%, average p = 1.07%) between Pygospio sp. 1 and P. elegans indicate a comparatively recent genetic divergence of the Pygospio population in the Sea of Okhotsk. Taking into account the high genetic similarity of the remote European and North American populations of P. elegans and medial location of the Pygospio sp. 1 population, we suggest the latter to belong to a separate species. However, this conclusion should be verified in further studies on the morphology, reproductive biology and genetics of this population. The present findings show the need to re-examine Pygospio from the Asian Pacific and elsewhere that have been identified as P. elegans. PMID- 27394229 TI - First stage larva of the mud shrimp Nihonotrypaea makarovi Marin, 2013
(Decapoda: Axiidea: Callianassidae) obtained in the laboratory. AB - First stage larva of a new mud shrimp Nihonotrypaea makarovi Marin, 2013 (Decapoda: Axiidea: Callianassidae) obtained from the ovigerous female is described and illustrated for the first time. The first zoea of N. makarovi is well distinguished from the first larvae of N. japonica and N. petalura, sympatric callianassid species inhabiting Russian waters of the Sea of Japan, only by the greater size and by the presence of two terminal setae on the antennal endopod. PMID- 27394230 TI - Brazilian dustywings (Neuroptera: Coniopterygidae): new species of Incasemidalis Meinander, 1972 and Coniopteryx Curtis, 1834, checklist and key for the Brazilian species. AB - Two subfamilies and three genera of Coniopterygidae have been reported to date for Brazil, with a total of 44 of species. In this paper two new Brazilian species are described from the genera Coniopteryx Curtis, 1834 and Incasemidalis Meinander, 1972-C. (Scotoconiopteryx) letardii sp. n. and Incasemidalis brasiliensis sp. n. -increasing the number of reported genera for Brazil to four and the number of Brazilian species to 46. This is the first report of Incasemidalis for Brazil. Moreover, in the case of C. (C.) callangana Enderlein, 1906, C. (Scotoconiopteryx) flinti Meinander, 1975, C. (S.) tucumana Navas, 1930, Semidalis nimboiformis Monserrat, 1989 and S. normani Meinander, 1982 some additional characteristics are given to the original descriptions or earlier redescriptions, with new records increasing their known distribution. An updated checklist of the Coniopterygidae from Brazil is provided, as well as a key for the Brazilian species of the family. PMID- 27394231 TI - Minooa Yamanaka, 1996, a genus newly recorded to China with description of a new species (Lepidoptera, Pyralidae, Pyralinae). AB - The genus Minooa Yamanaka, 1996 was monobasic with Minooa yamamotoi Yamanaka, 1996 as the type species. Previously, the genus was only recorded from Japan (Yamanaka 1996; Yamanaka & Yoshiyasu 2013). The diagnostic characters of this genus are as follows: antenna of male ciliated ventrally, simple in female; forewing M1 stalked with R3+4+5 for short distance, M2 and M3 stalked for 1/4 length; hindwing with Rs and M1 stalked, M2 and M3 stalked for 1/4 length; male genitalia with a long process arising from base of sacculus; aedeagus with several thorn-shaped cornuti; female genitalia with ductus bursae broadened and wrinkled posteriorly; signum formed by minute sclerites. PMID- 27394232 TI - First record of the Kuwana pine mealybug Crisicoccus pini (Kuwana) in Italy: a new threat to Italian pine forests? AB - The Asiatic Kuwana pine mealybug, Crisicoccus pini (Kuwana, 1902) (Hemiptera, Pseudococcidae), is reported in Italy for the first time. It was detected in September 2015 on maritime pine, Pinus pinaster, and stone pine, Pinus pinea, trees growing in the town of Cervia (Ravenna Province), Northern Italy. The mealybug has caused yellowing and decline of the pine trees. Pinus pinea is recorded here as a new host for C. pini. PMID- 27394233 TI - The effect of two fixation methods (TAF and DESS) on morphometric parameters of Aphelenchoides ritzemabosi. AB - Identification of nematode species by using conventional methods requires fixation of the isolated material and a suitable preparation for further analyses. Tentative identification using microscopic methods should also be performed prior to initiating molecular studies. In the literature, various methods are described for the preparation of nematodes from the genus Aphelenchoides for identification and microscopic studies. The most commonly used fixatives are formalin (Timm 1969; Szczygiel & Cid del Prado Vera 1981, Crozzoli et al. 2008, Khan et al. 2008), FAA (Wasilewska 1969; Vovlas et al. 2005, Khan et al. 2007) and TAF (Hooper 1958, Chizhov et al. 2006, Jagdale & Grewal 2006). PMID- 27394234 TI - The type specimens of Bebryce (Cnidaria, Octocorallia, Plexauridae) re-examined, with emphasis on the sclerites. AB - Nineteen species of Bebryce are re-described and scanning electron microscopy (SEM) images of sclerites presented. For B. sulfurea Grasshoff, 2000, this is the first time SEM images of sclerites are presented. Two new species are described, Bebryce asteria n. sp. and B. cofferi n. sp., and B. stellata Hentschel, 1903 is synonymized with B. studeri Whitelegge, 1897. Bebryce acanthoides Thomson & Russell, 1910 is referred to Discogorgia Kukenthal, 1919. The status of the original type material is discussed. PMID- 27394235 TI - New genera, species and records of Doryctinae (Hymenoptera: Braconidae) from Brazil. AB - Two new genera of Doryctinae (Hymenoptera: Braconidae) are described, Parsteres n. gen., Tuberatra n. gen., and are added to the identification key of Marsh (1997). Three new species are also described: P. pilosus n. sp., T. curvicauda n. sp., and Barbalhoa longicaudus n. sp. An identification key to the species of Barbalhoa Marsh, 2002 is presented, and nine species of the subfamily have their first record for Brazil. PMID- 27394236 TI - Two new species of Epimelitta Bates from Brazil and a new synonymy in
Stenopseustes Bates (Coleoptera, Cerambycidae, Cerambycinae, Rhinotragini). AB - Two new species of Epimelitta (Cerambycidae: Cerambycinae: Rhinotragini) are described from Brazil: E. prodigiosa sp. nov., from Espirito Santo, Rio de Janeiro and Sao Paulo and E. penicillata sp. nov., from Santa Catarina and Rio Grande do Sul. The larva and pupa of E. prodigiosa sp. nov. are also described and illustrated. Stenopseustes gibbicollis Fisher, 1947 is synonymized with S. aeger Bates, 1873. PMID- 27394237 TI - Taxonomic revision of Richardiodes Hendel (Diptera, Richardiidae). AB - Richardiodes Hendel is a genus scarcely known taxonomically and two species are recognized: Richardiodes rectinervis Hendel from Brazilian Amazon and R. trimaculata Hennig from Peru. Herein, these two species are revised and illustrated. Examination of non-type specimens revealed considerable variation in the general body color, and the geographic distribution of each species has been expanded, especially of R. rectinervis. The limits of the genus are revised and better supported with the addition of new diagnostic characters. The male and female terminalia are described and illustrated for the first time. PMID- 27394238 TI - Taxonomy of the Phyllotis osilae species group in Argentina; the status of the "Rata de los nogales" (Phyllotis nogalaris Thomas, 1921; Rodentia: Cricetidae). AB - The taxonomic status of populations of the genus Phyllotis from northwestern Argentina (NWA) has undergone recent changes, with the addition of two species (P. alisosiensis and P. anitae) to the traditionally recognized forms (P. caprinus, P. xanthopygus, and P. osilae). Three of these species (P. anitae, P. osilae, and P. alisosiensis) were included within the Phyllotis osilae species group. Most authors recognized three subspecies of P. osilae for NWA: P. osilae osilae, P. o. nogalaris, and P. o. tucumanus. Morphological, morphometric, and molecular studies based on recently collected specimens suggest that current classification does not reflect the diversity of this group in NWA, revealing the need of some taxonomic reallocations and new distributional delimitations. Here we propose that P. nogalaris must be recognized as a valid species and the restriction of P. osilae to southern Peru and central Bolivia. Following our results, we expect an outstanding improvement in the taxonomic knowledge of the Phyllotis osilae species group in the coming years. PMID- 27394239 TI - Neoelmis guarani Shepard & Barr, a sexually dimorphic new species from
Paraguay (Insecta: Coleoptera: Elmidae: Elminae). AB - Neoelmis guarani new species is described and illustrated from specimens collected in streams of the Cordillera de los Altos, southeast of Asuncion and near the towns of Piribebuy and Chololo, Paraguay. Males and females of this species exhibit strong secondary sexual dimorphism not found in other known species of Neoelmis. Males have striking modifications of the pro- and mesothoracic legs and bear a pair of ventrally projecting processes on both the mesoventrite and the second abdominal ventrite. Females have the elytra modified with a pair of dorsal projections. PMID- 27394240 TI - Blind life in the Baltic amber forests: description of an eyeless species of the ground beetle genus Trechus Clairville, 1806 (Coleoptera: Carabidae: Trechini). AB - The first eyeless beetle known from Baltic amber, Trechus eoanophthalmus sp. n., is described and imaged using light microscopy and X-ray micro-computed tomography. Based on external characters, the new species is most similar to species of the Palaearctic Trechus sensu stricto clade and seems to be closely related to the Baltic amber fossil T. balticus Schmidt & Faille, 2015. Due to the poor conservation of the internal parts of the body, no information on the genital characters can be provided. Therefore, the systematic position of this fossil within the megadiverse genus Trechus remains dubious. The occurrence of the blind and flightless T. eoanophthalmus sp. n. in the Baltic amber forests supports a previous hypothesis that these forests were located in an area partly characterised by mountainous habitats with temperate climatic conditions. PMID- 27394241 TI - A new Mexican species of Belonuchus Nordmann (Coleoptera, Staphylinidae). AB - A new species of Belonuchus Nordmann, 1837 is described based on 118 specimens from Cerro de Garcia, Jalisco, Mexico. Belonuchus cifuentesi Rodriguez & Navarrete-Heredia sp. nov. was primarily collected associated with Agave inaequidens, and is similar to B. arizonicus Casey, 1915 but differs mainly in the structure of the aedeagus and color pattern. PMID- 27394242 TI - Revision and phylogeny of the genus Balgus Fleutiaux, 1920 (Coleoptera, Elateridae, Thylacosterninae). AB - The genus Balgus Fleutiaux 1920 was currently comprised of nine species and can be easily distinguished from other Thylacosterninae by the presence of tubercles on the pronotal disk. In this paper a taxonomic revision and a reconstruction of the phylogeny of the genus were performed. Morphological data were analyzed using maximum parsimony (MP) and by Bayesian inference (BI). For BI the Mkv model was used. The genus Balgus and eight of the nine species were redescribed. The subspecies B. schnusei cayennensis Chassain, 2003 was considered a synonym of B. schnusei (Heller, 1914), and the genus was considered monophyletic. An identification key to all species of the genus was generated. PMID- 27394243 TI - A new species of nurse-frog (Aromobatidae, Allobates) from the Madeira River basin with a small geographic range. AB - I describe the seventh species of nurse-frog (Allobates) from the Madeira River basin in Brazilian Amazonia. The new species is distinguished from similar congeneric species by its small body size (snout-to-vent length ranging between 14.0-14.7 mm in adult males and between 14.7-14.9 mm in adult females), by the absence of dark brown regular shapes (e.g. hourglass, "X" or polygon-like marks) on the dorsum, by the absence of transverse dark bars on the dorsal surface of the thigh, and by the light gray to white ventral surfaces, light to dark gray only on throat in live male and female specimens. Males have a distinctive advertisement call characterized by the emission of long (7-11 s) trills of short notes (0.04 s in average) with dominant frequency at 5.9-6.3 kHz and emission rate ranging between 6.7-8.7 notes/s. DNA barcode analyses based on a fragment of the 16S rDNA mitochondrial gene provides additional support to the recognition of the new taxon, which is probably distributed on the east riverbank of the Madeira River, in the interfluve between the Aripuana and Ji-Parana rivers. PMID- 27394244 TI - A new species of Eidmanacris Chopard, 1956, with notes on its distribution in Brazilian caves (Phalangopsidae, Luzarinae). AB - The genus Eidmanacris comprises 19 species distributed through Brazil, Bolivia ad Paraguay. In Brazil, the genus has a broad distribution, but its occurrence in Brazilian caves is poorly known; the only species recorded is E. alboannulata for the cave "Gruta da Toca", Itirapina municipality, Sao Paulo State. In this study I describe a species, E. lencionii Bolfarini, n. sp., with a discussion on its distribution in Brazilian caves, and its relation with the hypogean environment. The type material is deposited in the Museu de Zoologia da Universidade de Sao Paulo (MZSP) and the Laboratorio de Estudos Subterraneos da Universidade Federal de Sao Carlos (LES/UFSCar). PMID- 27394245 TI - Taxonomic status of maskrays of the Neotrygon kuhlii species complex (Myliobatoidei: Dasyatidae) with the description of three new species from the Indo-West Pacific. AB - The bluespotted maskray, Neotrygon kuhlii (Muller & Henle, 1841), once thought to be widely distributed in the Indo-West Pacific, consists of a complex of several species and the type series consists of multiple species; its nomenclature is discussed. A lectotype and paralectotype are designated and the species rediagnosed based on the types and a fresh specimen from Honiara (Solomon Islands), near to the collection locality of the lectotype (Vanikoro, Solomon Islands). Molecular and morphological data provide confirmatory evidence that this maskray is distinct from some other regional forms. Three members of the complex from the Western Pacific identified in earlier studies are confirmed to be new species; Neotrygon australiae sp. nov. (Australia, New Guinea and eastern Indonesia), N. caeruleopunctata sp. nov. (Indian Ocean), and N. orientale sp. nov. (North-West Pacific). These species differ from each other and N. kuhlii in their adult size, anterior angle of the disc, number and distribution of blue spots on the dorsal disc, and other more subtle morphometric and meristic characters. Another largely plain-coloured Neotrygon, also currently misidentified as N. kuhlii, is sympatric with N. orientale sp. nov. in the South China Sea and off Taiwan. Neotrygon varidens (Garman) is resurrected as the valid name for this ray. A key is provided to species of the genus. PMID- 27394246 TI - A new jellynose, Ateleopus edentatus, from the western Pacific Ocean (Teleostei: Ateleopodiformes: Ateleopodidae). AB - Ateleopus edentatus sp. nov. is described based on 12 specimens collected from the Kyushu-Palau Ridge in the western Pacific Ocean. It is distinguished from its three known congeners in completely lacking upper-jaw teeth. It is also distinguished from Ateleopus indicus by having 94-130 anal+caudal-fin rays vs. 76 82 in A. indicus, 11-13 gill rakers vs. 7-8, and 26-28+81-107=109-135 vertebrae vs. 22-24+75-80=97-103. PMID- 27394247 TI - Five new species of freshwater crabs of the genera Ghatiana Pati & Sharma, 2014, and Gubernatoriana Bott, 1970 (Crustacea, Decapoda, Brachyura: Gecarcinucidae Rathbun, 1904) from the Western Ghats, India. AB - Five new species of gecarcinucid freshwater crabs, Ghatiana atropurpurea n. sp., Ghatiana splendida n. sp., Gubernatoriana alcocki Pati n. sp., Gubernatoriana thackerayi Pati n. sp., and Gubernatoriana waghi Pati n. sp. are described from the Western Ghats in Maharashtra and Goa states of India. Ghatiana atropurpurea n. sp. can be differentiated from other species of Ghatiana Pati & Sharma, 2014 by the shape and colour of its carapace, and the sigmoid-shaped male first pleopod (G1). Ghatiana splendida n. sp. is separated from its congeners mainly by its long anterolateral margin of the carapace and short terminal article of the G1. Besides, the colour pattern (deep pink carapace and chelipeds, orange ambulatory legs) of G. splendida n. sp. is exceptional among its congeners. Gubernatoriana alcocki n. sp. is unique among species of Gubernatoriana Bott, 1970 due to its inwardly curved tip of the terminal article of the G1. The stout and cone-shaped terminal article of the G1 of G. thackerayi n. sp. is characteristic among its congeners. In addition, G. thackerayi n. sp. has a unique colouration amongst congeners (violet-red carapace and ambulatory legs, orange-red chelipeds). Gubernatoriana waghi n. sp. can be distinguished from its congeners by the quadrate-shaped carapace, narrow frontal margin, pointed tips of the cheliped fingers, short terminal article of the G1 and very short or vestigial terminal article of the male second pleopod (G2). The body colour (burnt orange carapace and ivory coloured chelipeds and ambulatory legs) of G. waghi n. sp. is also important to distinguish live crabs of the genus. Key to the species of Ghatiana and Gubernatoriana is provided. PMID- 27394248 TI - A study of the genus Aphelocheirus (Hemiptera: Nepomorpha: Aphelocheiridae) from northern Vietnam, with descriptions of three new species. AB - Three new species, Aphelocheirus (s.str.) apicalis sp.n., A. (s.str.) flavinotatus sp.n., and A. (s.str.) sapa, sp.n. are described from northern Vietnam. Aphelocheirus (s.str.) lahu Polhemus & Polhemus, 1988 is reported from Vietnam for the first time. Additional distribution records of A. (s.str.) gularis Horvath, 1918 and A. (s.str.) inops Horvath, 1918 are provided. PMID- 27394249 TI - Taxonomic revision of the spider genus Rualena Chamberlin & Ivie 1942 and description of Hoffmannilena, a new genus from Mexico (Araneae: Agelenidae). AB - The genus Rualena Chamberlin & Ivie 1942 (Araneae: Agelenidae) is revised and a new genus, Hoffmannilena, is described. Four new species are described for Rualena: R. cedros sp. nov. (? ?), R. parritas sp. nov. (? ?), R. thomas sp. nov. (? ?), and R. ubicki sp. nov. (?). The males of R. alleni Chamberlin & Ivie 1942 and R. avila Chamberlin & Ivie 1942 and the female of R. rua (Chamberlin 1919) are described for the first time. Rualena goleta Chamberlin & Ivie 1942 is a junior synonym of R. surana Chamberlin & Ivie 1942. Rualena cavata (F.O. Pickard Cambridge 1902) and R. pasquinii Brignoli 1974 are considered incertae sedis. Two species are transferred from Rualena to Novalena Chamberlin & Ivie 1942: N. shlomitae (Garcia-Villafuerte 2009) comb. nov. and N. simplex (F.O. Pickard Cambridge 1902) comb. nov. For Hoffmannilena gen. nov., five new species are described: H. apoala sp. nov. (?), H. cumbre sp. nov. (? ?), H. huajuapan sp. nov. (?), H. mitla sp. nov. (?), and H. tizayuca sp. nov. (? ?). Three species are transferred from Novalena to Hoffmannilena gen. nov.: H. lobata (F.O. Pickard Cambridge 1902) comb. nov., H. marginata (F.O. Pickard-Cambridge 1902) comb. nov., and H. variabilis (F.O. Pickard-Cambridge 1902) comb. nov. Novalena cuspidata (F.O. Pickard-Cambridge 1902) is a junior synonym of H. marginata. PMID- 27394250 TI - Cassidinae (Coleoptera: Chrysomelidae) types deposited at Sun Yat-sen
University, Guangzhou, China. AB - Type specimens of Cassidinae deposited at Sun Yat-sen University, Guangzhou, China were studied and as a result following new synonymies are proposed: Cassida expansa Gressitt, 1952 = C. smaragdocruciata Medvedev & Eroshkina, 1982 syn. nov.; C. concha Solsky, 1872 = C. juglans Gressitt, 1942 syn. nov.; Rhoptrispa dilaticotnis (Duvivier, 1891) = Rhadinosa abnormis Gressitt & Kimoto, 1963 syn. nov. Lasiochila fukiena Gressitt, 1950 stat. nov. is removed from synonymy of L. insulana Uhmann, 1929. Each taxon is provided with photograph of dorsal habitus and additional comment clarifiyng its status where necessary. PMID- 27394251 TI - Cryptic diversity in the Hypsiboas semilineatus species group (Amphibia, Anura) with the description of a new species from the eastern Guiana Shield. AB - We used molecular and morphological data to investigate the hidden diversity within the Hypsiboas semilineatus species group, and more specifically within H. geographicus, an allegedly widespread species in northern South America. As a result, the identity of H. geographicus was clarified, several candidate species were detected and one of them, from the eastern Guiana Shield, is described herein as a preliminary step to resolve the taxonomy of the group. Hypsiboas diabolicus sp. nov. is mainly distinguished from closely-related species by an acuminate snout in lateral view, well-developed webbing between fingers and toes, and unspotted carmine/crimson colouration on the concealed surfaces of legs, feet and hands in life. The tadpole of the new species is described and is characterized by a large A-2 gap, a mostly single row of large marginal papillae, and a dark brown to black colouration. We also describe the advertisement call of the new species, which is defined as a soft call consisting of short clusters of 2-3 chuckles with a dominant frequency ranging between 1.11-1.19 kHz. Hypsiboas diabolicus sp. nov. is currently known only from the eastern Guiana Shield, and is probably endemic to that region. The new species' range overlaps broadly with another candidate species referred to as H. aff. semilineatus 1. Our preliminary results stress out a high cryptic diversity in that species group and the need for a formal redescription of Hypsiboas geographicus based on more topotypic material than what is currently available to properly sort out the taxonomic status of several lineages in that clade. PMID- 27394252 TI - Taxonomic study of the genus Lycophantis Meyrick from China (Lepidoptera: Yponomeutidae) with descriptions of three new species. AB - Six Chinese species of the genus Lycophantis Meyrick, 1914 are reviewed, including three new species: Lycophantis mucronata Li, sp. nov. from Zhejiang and Hubei, L. stenopetala Li, sp. nov. and L. incurvula Li, sp. nov., both from Xizang (Tibet). Lycophantis leviaurata Sohn & Park, 2010 is newly recorded from China. Images of adults and genitalia are provided, along with key to all the Chinese species of Lycophantis. PMID- 27394253 TI - Three new species of Oxysarcodexia Townsend (Diptera: Sarcophagidae)
from the Colombian Andes. AB - Three new species of Oxysarcodexia Townsend (Diptera: Sarcophagidae) from the Colombian Andes are described based on male specimens collected using decaying animal matter as bait: Oxysarcodexia catica sp. n., O. laclaricola sp. n., and O. liliarum sp. n. The straight and narrow cercal prong with an acute apex, and the juxta enlarged distally and folded backwards of O. catica sp. n. resemble these structures in O. fraterna Lopes, O. peruviana (Lopes) and O. vittata (Walker). The shape of the cercus of O. laclaricola sp. n. is similar to that of O. floricola Lopes, whereas its vesica is similar in shape to that of O. cyaniforceps (Hall). Oxysarcodexia liliarum sp. n. resembles O. favorabilis (Lopes) in the inflorescence-like phallus and enlarged juxta. The postero-distal phallic enlargement of O. catica sp. n. and O. liliarum sp. n. support the inclusion of these species in the so-called "Xarcophaga group" (sensu Lopes). PMID- 27394254 TI - Two new species of Tomocerus ocreatus complex (Collembola, Tomoceridae) from Nanjing, China. AB - Two new species of Tomocerus Nicolet, 1842 are described from Nanjing, China. Tomocerus qinae sp. nov. is similar to the Vietnamese species Tomocerus ocreatus, but is different from the latter mainly in the colour pattern, the length of antennae, and the pattern of ungual teeth. Tomocerus qixiaensis sp. nov. is similar to Tomocerus ocreatus and Tomocerus qinae sp. nov., but can be distinguished from them by the short antennae and the blunt prominent macrochaetae on manubrium and dens. DNA barcode sequences of the new species are provided. PMID- 27394255 TI - Emschermannia ramificata-a new genus and species of solitary entoproct from the Kara Sea, Russia. AB - A new genus and species of solitary entoproct, Emschermannia ramificata, is described from the Kara Sea. It is an epibiont of the nephtyid polychaete Aglaophamus malmgreni, collected from 25-472 m depth. The species is about 250 300 MUm long, with 8-10 tentacles, and buds are formed from a frontal area of the calyx. The calyx and stalk are not separated from each other by a cuticular septum, and a star-cell complex is absent. Emschermannia ramificata attaches to a substratum via a basal plate from which pseudostolons grow. Zooidal morphology conforms to that of the Loxosomatidae, but the attachment structure is unique among solitary entoprocts; it resembles basal plates and stolons of colonial entoprocts, but pseudostolons of Emschermannia serve only for attachment, not for budding. Overall, the morphology of Emschermannia may be considered intermediate between that of solitary and colonial forms, with relevance to evolutionary development within Entoprocta. PMID- 27394256 TI - A new subspecies of Chlaenius (Chlaeniellus) laeviplaga Chaudoir, 1876 (Coleoptera: Carabidae: Licininae) from South Iran. AB - A new subspecies of Chlaenius (Chlaeniellus) laeviplaga Chaudoir, 1876, namely Chlaenius (Chlaeniellus) laeviplaga gambronicus ssp. n., is described from South Iran, Hormozgan province. A key for the identification of the subspecies of laeviplaga is provided. PMID- 27394257 TI - Indels ascertain the phylogenetic position of Coleodactylus elizae Goncalves, Torquato, Skuk & Sena, 2012 (Gekkota: Sphaerodactylidae). AB - The Neotropical gecko genus Coleodactylus Parker 1926 was, until recently, composed of five species: C. amazonicus (Andersson 1918), C. brachystoma (Amaral 1935), C. meridionalis (Boulenger 1888), C. natalensis Freire 1999, and C. septentrionalis Vanzolini 1980 (Geurgas et al. 2008). However, several phylogenetic analyses recovered a polyphyletic Coleodactylus (Geurgas et al. 2008; Gamble et al. 2011a) leading Gamble et al. (2011b) to recognize a new genus, Chatogekko, for C. amazonicus. Coleodactylus and Chatogekko differ in both morphological and molecular characters. Coleodactylus has smooth dorsal scales and five scales forming the ungual sheath, while Chatogekko has keeled dorsal scales and four scales forming the ungual sheath (Gamble et al. 2011b). Furthermore, all Coleodactylus species have two deletions in the protein coding recombination-activating gene 1 (RAG1), one of six base pairs (bp) and another of 18 bp (Gamble et al. 2008a; Geurgas et al. 2008), while Chatogekko has a unique three bp deletion in the RBMX gene and a three bp deletion in the protein tyrosine phosphatase nonreceptor type 12 gene (PTPN12) (Gamble et al. 2011b). In addition, Chatogekko is differentiated from all others geckos by a unique set of 10 craniofacial features (Gamble et al. 2011b). PMID- 27394258 TI - The Heteromurini Absolon & Ksenemann (Collembola, Entomobryidae):
a review of the genera status and diagnoses, keys for species of Alloscopus Borner and Heteromurtrella Mari Mutt and description of a new species. AB - The status of Heteromurini Absolon & Ksenemann is analyzed and a new diagnosis is proposed to the tribe. New chaetotaxic characteres were added to distinguish Dicranocentrus Schott and Pseudodicranocentrus Mari Mutt. Alloscopus Borner, Heteromurtrella Mari Mutt and Verhoeffiella Absolon, originally proposed as subgenera of Heteromurus Wankel, are reviewed and a new diagnosis and generic status are proposed. The presence of the postantennal organ becomes the main characteristic to distinguish Alloscopus (present) and Heteromurtrella (absent). Alloscopus yosiius Mari Mutt, anteriorly synonymized with Alloscopus tenuicornis Borner, is revalidated. The absence of S0 macrochaeta on head of Heteromurus is reported now as a characteristic also shared with Heteromurtrella. Heteromurtrella zairensis Tshelnokov comb. nov. is transferred from Heteromurus by the presence of macrochaetae on abdomen I. Heteromurtrella anae sp. nov. from Brazilian Amazon is described and illustrated, including detailed dorsal chaetotaxy. This is the first record of Heteromurtrella in Brazil. Heteromurus now has 17, Alloscopus 10 and Heteromurtrella 20 valid species worldwide. An identification key and diagnosis for the six genera of Heteromurini and species of Alloscopus and Heteromurtrella are provided. PMID- 27394259 TI - Revision of the Caraphiini, New Tribe (Coleoptera, Cerambycidae, Lepturinae). AB - Caraphiini N. Ohbayashi, Lin & Yamasako, trib. nov. of the subfamily Lepturinae is erected for the genus Caraphia Gahan, 1906. The Central American genus Noctileptura Chemsak & Linsley, 1984 is synonymized with the southeast Asian genus Caraphia. Caraphia huai N. Ohbayashi & Lin, sp. nov., from Hainan and Guangdong, China, Caraphia paulastoni N. Ohbayashi & Lin, sp. nov. from Hong Kong, China and Caraphia lingafelteri N. Ohbayashi & Yamasako, sp. nov. from Matagalpa, Nicaragua are described. All the known sixteen species of the newly defined genus Caraphia are revised with a key and their habitus. PMID- 27394260 TI - Neoplasta Coquillett (Diptera: Empididae: Hemerodromiinae) from Brazil:
new species and male description of N. fortiseta Smith. AB - Neoplasta Coquillett is distributed in the New World. The male of N. fortiseta Smith and five new species collected in the Brazilian states of Santa Catarina and Sao Paulo (N. lobata sp. nov., N. longicornis sp. nov., N. macdonaldi sp. nov., N. nigrithorax sp. nov., and N. spinulosa sp. nov.), are described and illustrated. A key to Brazilian species is provided. PMID- 27394261 TI - The earwig fauna (Insecta: Dermaptera) of Penang Island, Malaysia, with descriptions of two new species. AB - The earwig (Dermaptera) fauna of Penang Island, Malaysia, was evaluated by means of an extensive field survey together with revision of the few published data. Based on the results of the field survey, 31 species are recognized (2 Diplatyidae, 3 Pygidicranidae, 5 Anisolabididae, 2 Labiduridae, 14 Spongiphoridae, 4 Chelisochidae, 1 Forficulidae). Fifteen of these taxa are new to Peninsular Malaysia (=West Malaysia): Diplatys annandalei Burr, 1911, Diplatys mutiara n. sp., Euborellia philippinensis Srivastava, 1979, Metisolabis punctata (Dubrony, 1879), Pseudovostox brindlei Srivastava, 2003, Chaetospania anderssoni Brindle, 1971, Chaetospania javana Borelli, 1926, Chaetospania huisiangi n. sp., Paralabellula boettcheri (Borelli, 1923), Paralabellula rotundifrons (Hincks, 1954), Nesogaster amoenus (Stal, 1855), Hamaxas crassus Borelli, 1926, Proreus coalescens (Borelli, 1927), Hypurgus humeralis (Kirby, 1891), and an unidentified Echinosoma sp. Species composition of the island are compared with the dermapteran fauna of Thailand. Descriptions of females (or female genitalia) are given for some species for the first time. PMID- 27394262 TI - Advertisement call of Scinax camposseabrai (Bokermann, 1968) (Anura: Hylidae), with comments on the call of three species of the Scinax ruber clade. AB - Scinax camposseabrai was allocated into the Scinax ruber clade by Caramaschi & Cardoso (2006) by overall similarities as snout not pointed, breeding in open areas, and an advertisement calls with multipulsed notes. This assumption about the call was based solely on an onomatopoeia provided by Bokermann (1968). Herein we provide a formal description of the advertisement call of S. camposseabrai and compare it with described calls of other S. ruber clade species. Additionally, we provide descriptions of the advertisement calls of three sympatric species of the S. ruber clade: S. eurydice (Bokermann), S. pachycrus (Miranda-Ribeiro) and S. cf. x-signatus. PMID- 27394263 TI - A new species of Cymodoce from Iran (Crustacea: Isopoda: Sphaeromatidae) with remarks on the status of Cymodoce manorii (Nooruddin, 1965) comb. nov. and Cymodoce spinula Yousuf & Javed, 2001. AB - Cymodoce brucei sp. nov. is described from the intertidal zone of the Iranian coast of the Oman Sea. This species can be distinguished from all other Cymodoce in the Western Indian Ocean region, by a pleotelson with a large prominent tongue like projection in midline of the posterior margin. The status of Cerceis manorii Nooruddin, 1965, and Cymodoce spinula Yousuf & Javed, 2001 both from Pakistan (Karachi) is determined and Cymodoce manorii (Nooruddin, 1965) comb. nov. is established. PMID- 27394264 TI - The description of a new calyptrate fly mimicking species of the fungus weevil genus Gymnognathus Schonherr 1826 from the southern Bolivian Andes (Coleoptera: Anthribidae: Anthribinae). AB - A new calyptrate fly mimicking species of Gymnognathus Schonherr 1826 from the humid Tucuman-Bolivian forest in the southern Bolivian Andes is described. Gymnognathus barclayi sp. nov. is distinguished from the closest related species G. bohlsi Jordan, 1895, by the color and/or distribution of the scales on the pronotum, fourth ventrite and pygidium, the wider pronotum and the development of the spines on the pygidium. The arrangement of the longitudinal stripes on the pronotum suggests that G. barclayi sp. nov. is a mimic of tachinid or muscid flies. The almost exclusive occurrence of Gymnognathus species in tropical moist forests indicates that the presence of G. barclayi sp. nov. in the subtropical realm is fostered by increased humidity at orographic rain barriers. G. barclayi sp. nov. is possibly endemic to the Tucuman-Bolivian forest. Along with the presence of other endemic species, the discovery of G. barclayi sp. nov. highlights the importance of the Tucuman-Bolivian forest as an endemism hotspot for insects and calls for a re-assessment of the conservation status of this spatially restricted and threatened ecoregion. PMID- 27394265 TI - A new millipede, Austrotyla awishoshola n. sp., (Diplopoda, Chordeumatida, Conotylidae) from New Mexico, USA, and the importance of cave moss gardens as refugial habitats. AB - Austrotyla awishoshola n. sp. is described from the moss gardens of one lava tube cave in El Malpais National Monument, Cibola Co., New Mexico. Most chordeumatidans require mesic conditions, and these environments are limited to moss gardens in several cave entrances and beneath cave skylights in El Malpais. Presently, this species is known from the moss gardens of a single of cave in the monument. We suggest A. awishoshola may be a climatic relict, having become restricted to the cave environment following the end of the Pleistocene. We discuss the importance of cave moss gardens as refugial and relictual habitats. Recommendations are provided to aid in the conservation and management of A. awishoshola and these habitats. PMID- 27394266 TI - Studies in Guatemalan Ensifera: Mayacephalus (Orthoptera: Tettigoniidae) a new cone-headed katydid genus. AB - Mayacephalus dickmanorum n. gen. et n. sp., from eastern Guatemala is described in this contribution. This new genus highlights from other related ones by its short tegmina; unusual for the tribe Copiphorini, and only present in three neotropical genera: Toledopizia, Brachycaulopsis and Daedalellus, being closer to the first one. PMID- 27394267 TI - The Cylapinae (Insecta, Hemiptera, Heteroptera: Miridae) of India: review of the subfamily with description of new species. AB - The subfamily Cylapinae (Insecta, Heteroptera: Miridae) from India is reviewed. Three tribes, seven genera and nineteen species are cited from the country, keyed and described. Six species are described as new: Fulvius kadapaensis sp. nov., Peritropis kodava sp. nov., Peritropis pathaki sp. nov., Peritropis sangai sp. nov., Peritropis yasunagai sp. nov. and Rhinomiris prathapani sp. nov. A new synonymy is published: Peritropis lewisi (Distant, 1904) (valid name) = Peritropis indicus Gorczyca, 2006b (new junior subjective synonym). PMID- 27394268 TI - Rhigognostis senilella (Zetterstedt, 1839) and R. marmorosella (Wocke, 1849): two valid species distinguishable in genitalia (Lepidoptera, Plutellidae). AB - Rhigognostis senilella was described from Greenland over 150 years ago by Zetterstedt. Its historical range of distribution included also mountains in most of Europe. It was classified in Europe as a boreal-alpine zoogeographic element. Analysis of the structure of the male and female genitalia over its historical range shows that two distinct species are present. The range of R. senilella (Zetterstedt, 1839) is limited to Greenland and Iceland, whereas the mountains of Europe are inhabited by R. marmorosella (Wocke, 1849). The paper includes keys to distinguish these two species, one based on external characters, another on male or female genitalia. PMID- 27394269 TI - An illustrated catalogue of the types of Stratiomyidae (Diptera: Brachycera) in the collection of Museu Nacional, Rio de Janeiro, Brazil. AB - A catalogue of the type specimens of Stratiomyidae (Diptera: Brachycera) held in the collection of Museu Nacional, Rio de Janeiro, Brazil (MNRJ) is presented. A total number of 50 type specimens of 18 valid Neotropical species were recognized and are listed in alphabetical order of subfamily, genus and specific epithet. Photos of 12 primary types of the species and bibliographical data of the original descriptions, labels and condition of all type specimens are also provided. PMID- 27394270 TI - Notes on Oriental and East Palaearctic Manota Williston (Diptera, Mycetophilidae), with the description of seven new species. AB - The following new species of Manota are described: M. adunca (Taiwan), M. incilis (Nepal), M. integra (China), M. mitrata (China), M. nepalensis (Nepal), M. tayal (Taiwan) and M. vesca (Philippines). New records of the following species are given: M. acutangula Hippa (China, Taiwan), M. curvistylus Hippa, Kjaerandsen and Saigusa (China), M. oblonga Hippa (China), M. perlobata Hippa (China) and M. planilobata Hippa (China). Characters of the Chinese material of M. curvistylus are discussed and drawings of the hypopygium of a Chinese specimen are given. PMID- 27394271 TI - Five species of the genus Epicephala Meyrick, 1880 (Lepidoptera: Gracillariidae) from China. AB - Five species of the genus Epicephala Meyrick, 1880 are reported based on specimens collected from leaves or reared from fruits of different Glochidion plants (Phyllanthaceae) in southern part of China. Epicephala duoplantaria Li, sp. nov., E. daltonii Li, sp. nov., E. jianfenglingina Li, sp. nov. and E. assamica Li, sp. nov. are described as new; E. ancylopa Meyrick, 1918 is redescribed and recorded from China for the first time. Photographs of adults and genital structures are provided. PMID- 27394272 TI - Description of a new species of the genus Ptychozoon (Squamata: Gekkonidae), representing a new national record of this genus from southern Yunnan Province, China. AB - A new species of the Parachute Gecko, Ptychozoon bannaense sp. nov., is described on the basis of two specimens from Xishuangbanna, Yunnan Province, China. The new species can be distinguished from eight known congeners by the following combination of morphological characters: body size moderate, SVL 83.2-87.5 mm; rostral with a short dorsomedian groove; dorsal head and body covered with granular scales without enlarged tubercles, but male with several enlarged tubercles on the occipital region; two supranasals separated from each other by a large internasal; the absence of a predigital notch in the preantebrachial cutaneous flap; male possesses 17 preanofemoral pores in a continuous scale row; tail tubercle absent, 24 pairs of lateral denticulate cutaneous lobes of the tail; width of tail and caudal lobes progressively decreasing posteriorly; the terminal caudal flap short, semicircle, not expanded; lack of lobe fusion at the terminal caudal flap border; the presence of four dark dorsal bands between fore- and hind limbs insertions, the third and fourth dorsal bands fused into a X shaped mark. The new species is also divergent from known taxa in mitochondrial gene sequences, supporting its recognition based on morphological characters. The discovery and description of Ptychozoon bannaense brings the total number of Ptychozoon to nine, and represents the first record of the genus Ptychozoon in China. PMID- 27394273 TI - A new species of Odorrana (Amphibia: Anura: Ranidae) from Vietnam. AB - A new species of Odorrana is described from the karst forests in northeastern Vietnam based on morphological differences and molecular divergence. Morphologically, the new species is distinguishable from its congeners on the basis of a combination of the following diagnostic characters: (1) size large (SVL 85.9-91.6 mm in males, 108.7-110.1 mm in females); (2) head longer than wide; (3) vomerine teeth present; (4) external vocal sacs absent; (5) snout short (SL/SVL 0.16-0.17); (6) tympanum large (TD/ED 0.70 in males, 0.68 in females); (7) dorsal surface of head and anterior part of body smooth, posterior part of body and flanks with small tubercles; (8) supratympanic fold present; (9) dorsolateral fold absent; (10) webbing formula I0-0II0-0III0-1/2IV1/2-0V; (11) in life, dorsum green with dark brown spots; (12) flanks greyish brown with dark brown spots; (13) throat and chest grey, underside of limbs with large dark brown spots, edged in white, forming a network. In the phylogenetic analyses, the new species is unambiguously nested within the O. andersonii group, and placed as the sister taxon to O. wuchuanensis. PMID- 27394274 TI - A new species of Oozetetes De Santis (Hymenoptera: Chalcidoidea: Eupelmidae) from Colombia with an updated key for the bucheri species-group. AB - Oozetetes lucidus sp. nov. (Hymenoptera: Eupelmidae) is described from Colombia, South America, and through macrophotography compared with all described species in the bucheri species-group of Oozetetes De Santis. An illustrated key modified from Gibson (2004) is provided to distinguish females of the six described species of this group. PMID- 27394275 TI - A checklist of Indian armored spiders (Araneae, Tetrablemmidae) with the description of a new species from the Western Ghats. AB - The Oriental armored spider genus Shearella Lehtinen, 1981 is recorded for the first time from India. Detailed description and illustrations of both sexes of Shearella alii sp. nov. are given. The geographic distribution of the genus is updated. Sinamma sanya (Lin & Li, 2010) is transferred back to Shearella, and Shearella browni (Shear, 1978) back to Monoblemma Gertsch, 1941. A checklist of all Indian tetrablemmid species currently known and a distribution map of all known Shearella spp. are presented. PMID- 27394276 TI - A systematic review of the subfamily Syringophilinae (Acari: Syringophilidae) of the Nearctic region. Part 1: quill mites associated with passerines (Aves: Passeriformes). AB - Quill mites belonging to the subfamily Syringophilinae Lavoipierre, 1953 associated with the Nearctic passeriform birds are revised. All of the 49 known species, which are grouped in seven genera, are recorded. Among them, four new species are described: Syringophiloidus audubioni sp. nov. from Spizella breweri (Cassini) (Emberizidae), Syringophilopsis catesbyi sp. nov. from Vireo olivaceus (Linnaeus) (Vireonidae), S. wilsoni sp. nov. from Pheucticus melanocephalus (Swainson) (Cardinalidae), and S. bartrami sp. nov. from Spizella passerina (Bechstein) (Emberizidae). The species Syringophilopsis hylocichlae Clark, 1964 syn. nov. is synonymized with Syringophilopsis turdus (Fritsch, 1958), and Syringophiloidus zonotrichia syn. nov. is synonymized with Betasyringophiloidus seiuri (Clark, 1964) comb. nov. Six species are recorded from the Nearctic region for the first time: Syringophiloidus delichonum Bochkov, 2001, S. glandarii (Fritsch, 1958), S. weiszii Skoracki et al., 2001, S. bombycillae Skoracki, 2002, Syringophilopsis mimidus Sikora et al., 2011, and Torotrogla merulae Skoracki et al., 2000. Data on Nearctic syringophiline species, their hosts and distribution are summarized and the keys to all species are constructed. PMID- 27394277 TI - Parathelphusa pardus, a new species of lowland freshwater crab from swamps in central Sumatra, Indonesia (Crustacea: Brachyura: Gecarcinucidae). AB - A new species of gecarcinucid freshwater crab of the genus Parathelphusa H. Milne Edwards, 1853, is described from freshwater swamp habitats in Pekanbaru, Riau Province, in central-eastern Sumatra, Indonesia. Parathelphusa pardus sp. nov., has a very distinctive colour pattern, and in this respect, resembles P. maindroni (Rathbun, 1902) from Sumatra and Peninsular Malaysia; P. batamensis Ng, 1992, from Batam Island, Indonesia; P. reticulata Ng, 1990, from Singapore; and P. oxygona Nobili, 1901, from western Sarawak. It can be distinguished from these species and congeners by a suite of carapace, ambulatory leg, thoracic sternal and most importantly, male first gonopod characters. PMID- 27394278 TI - Redescription of Urophycis brasiliensis (Kaup 1858), a senior synonym of Urophycis latus Miranda Ribeiro 1903 (Gadiformes: Phycidae). AB - Urophycis Gill 1864 is a genus of demersal fish composed by eight valid species with anti-tropical distributions in the western Atlantic. Only two species occur in the South Atlantic: U. brasiliensis (Kaup 1858) and U. mystacea Miranda Ribeiro 1903. These species have similar ranges from southeastern Brazil to northern Argentina, but U. brasiliensis occurs in more shallow waters than U. mystacea. Both species are important fishery resources in southern Brazil and Uruguay. Herein, we redescribe U. brasiliensis based on comparison of types and additional specimens, including the description of the Sagitta otolith, formerly place U. latus Miranda Ribeiro 1903 as a junior synonym of U. brasiliensis, and provide an updated map of distribution. PMID- 27394279 TI - Mesoplophoroidea (Acari, Oribatida) of China. AB - The oribatid mite superfamily Mesoplophoroidea (Acari, Oribatida) is reviewed. Seven species in four genera of Mesoplophoroidea from China, including a new species, Mesoplophora (Mesoplophora) heterotricha sp. nov. from Hainan Province, are identified. Tritonymph of Apoplophora pantotrema (Berlese, 1913) is described based on material from China. A comprehensive, fully referenced checklist of all known species and keys to all known species worldwide are provided to facilitate the further study on this group. PMID- 27394280 TI - Carnidae (Diptera) in the Canadian National Collection of Insects (Ottawa), with the description of five new species. AB - The previously unidentified Carnidae in the Canadian National Collection of Insects (Ottawa) have been investigated. All faunistic records of 26 species are presented in this paper. Hemeromyia alberichae spec. nov. (USA), Meoneura hobbitoides spec. nov. (USA), Meoneura swifti spec. nov. (USA), Meoneura tinkerbellae spec. nov. (Canada), and Meoneura yodai spec. nov. (Canada) are described. First records are reported for Argentina, Canada, and Lebanon. PMID- 27394281 TI - The Mimallonidae (Lepidoptera, Mimallonoidea) of the Caribbean Basin,
with the descriptions of two new species. AB - Mimallonidae of the Caribbean Basin are discussed, with attention primarily given to species endemic to the Caribbean islands and the northern coast of Venezuela. The Caribbean Basin is a political term for tropical regions circumscribed by the Gulf of Mexico. Cicinnus bahamensis sp. n. is described from the Bahamas, the first species of Mimallonidae from this country. The Cuban species Cicinnus packardii (Grote, 1865), the closest relative of C. bahamensis sp. n., is figured and compared. A third, similar, species from northern coastal Venezuela, C. falcoargenteus sp. n., is described and compared to the previous two species. PMID- 27394282 TI - Taxonomy of 'Euconnus complex'. Part VII. Glabriconnus, a new subgenus of Euconnus from Madagascar (Coleoptera, Staphylinidae, Scydmaeninae). AB - A new subgenus of Euconnus Thomson is described, Glabriconnus subgen. n., to accommodate four Madagascan species: Euconnus banari sp. n. (type species of Glabriconnus), E. andranomenaus sp. n., E. februarius sp. n. and E. aterrimus Franz (transferred from Euconnus s. str.). Morphological structures of the new taxa are illustrated and described in detail, and possible relationships of Glabriconnus are discussed. The new subgenus is most similar to Tetramelus Motschulsky and Paratetramelus Franz in gradually thickened antennae and reduction of wings and associated structures, but the four species included in Glabriconnus share a unique synapomorphy, a hypomeral groove at each side of pronotum. They also have a broad, short and flattened 'anthiciform' head; nearly glabrous head, pronotum and elytra, except for thick bristles on genae, postgenae (but not tempora) and along anterior and lateral pronotal margins, and pronotum with one pair of distinct lateral pits. PMID- 27394283 TI - Severnsia strombeulima n. gen. & sp. from Hawaii (Mollusca, Gastropoda: Caenogastropoda: Eulimidae). AB - The malacofauna of Hawaii is rather well-known, owing to Kay (1979) and Severns (2011). Both works stand out because they include a large number of the generally under-represented micromollusks (<5 mm). Here a striking new genus and species of a microsnail is reported from that region. PMID- 27394284 TI - Prestonellinae-validation of the name as a new subfamily of Bothriembryontidae (Mollusca, Gastropoda, Orthalicoidea). AB - The affinities of the enigmatic South African land snail genus Prestonella Connolly, 1929 were discussed by Herbert (2007) and Herbert & Mitchell (2009), who showed, on the basis of morphological and molecular data, that the genus is referable to the superfamily Orthalicoidea. Currently, the three described species of Prestonella are the only known African representatives of this diverse superfamily. Earlier, van Bruggen (1978) had recognized that these species formed a distinct group and had placed them in the (new) family Prestonellidae. However, as noted by Bouchet & Rocroi (2005: 140), no diagnosis was provided by van Bruggen; the name Prestonellidae thus does not meet the requirements of ICZN Art. 13.1, and is not an available name. In this paper we will redress this issue, also taking into account more recent research which has shed light on the systematic position of this genus within the Orthalicoidea. PMID- 27394285 TI - Historical analysis of the type species of the genus Trichobilharzia Skrjabin et Zakharov, 1920 (Platyhelminthes: Schistosomatidae). AB - Trichobilharzia Skrjabin & Zakharov, 1920 is known as the most species-rich genus of the blood fluke family Schistosomatidae. To date, more than 40 species have been described, even though validity of some of them is questionable (Horak et al. 2002). Members of the genus use various birds as final hosts, but they attract attention mostly as causative agents of hypersensitive skin reaction (cercarial dermatitis or swimmer's itch) in mammals including humans. As this is one of the. PMID- 27394286 TI - Erections of Changa gen. nov. and Songga gen. nov. of Aolina (Hemiptera: Cicadidae: Cicadinae: Dundubiini) with taxonomic notes and a synonymization. AB - Two new genera, Changa gen. nov. and Songga gen. nov., are erected in the subtribe Aolina Boulard, 2012, with the designations of Cosmopsaltria sita Distant, 1881 and Pomponia scitula Distant, 1888 as the type species, respectively. Khimbya sita (Distant, 1881) becomes Changa sita (Distant, 1881) comb. nov. Haphsa scitula (Distant, 1888) becomes Songga scitula (Distant, 1888) comb. nov. Haphsa jsguillotsi (Boulard, 2005) is transferred to Changa to become Changa jsguillotsi (Boulard, 2005) comb. nov. Haphsa stellata Lee, 2009 syn. nov. is synonymized with Changa sita. Haphsa sulaeyai (Boulard, 2005) is transferred to Macrosemia Kato, 1925 to become Macrosemia sulaeyai (Boulard, 2005) comb. nov. A revised key to the genera of Aolina is provided. PMID- 27394287 TI - The millipede family Polydesmidae in the Caucasus (Diplopoda: Polydesmida). AB - The family Polydesmidae is represented in the Caucasus by two genera and 11 species: Polydesmus abchasius Attems, 1898, P. lignaui Lohmander, 1936, P. muralewiczi Lohmander, 1936 and P. mediterraneus Daday, 1889 (all confined to the NW and W Caucasus, but of which only the former three are endemic to the region, whereas the latter species is an introduction), as well as Brachydesmus assimilis Lohmander, 1936 (endemic to most of the region, except Hyrcania), B. pigmentatus Attems, 1951 (= B. pereliae Golovatch, 1976, syn. n.) (subendemic to Hyrcania), B. superus Latzel, 1884 (a cosmopolitan introduction), B. furcatus Lohmander, 1936 (= B. furcatus exiguus Strasser, 1970, syn. n.) (endemic to the NW Caucasus), B. kalischewskyi Lignau, 1915 (= B. karawajewi Lohmander, 1928, = B. ferrugineus Lohmander, 1936, = B. talyschanus Lohmander, 1936, = B. bidentatus Golovatch, 1976, all syn. n.) (a highly polymorphous and widespread species, apparently in a stage of active speciation, subendemic to the entire region), B. kvavadzei sp. n., from Ajaria, Georgia, and B. simplex sp. n., from Abkhazia and Sochi, Krasnodar Province, Russia. All known Caucasian species of Polydesmidae are described in due detail, abundantly illustrated and keyed, and their distributions mapped. PMID- 27394288 TI - Characterization of Platymessa with redescription of the type species and a new generic synonymy (Arachnida, Opiliones, Cosmetidae). AB - The genus Platymessa was originally described by Mello-Leitao and diagnosed following the Roewerian system. It originally included two species from the Colombian Andes. Subsequently, a third species was described: Platymessa transversalis Roewer, 1963, which is herein transferred to the genus Chusgonobius Roewer, 1952, forming the new combination Chusgonobius transversalis. Herein, an emended diagnosis is given to Platymessa, the type species, Platymessa h inscriptum Mello-Leitao, 1941, is redescribed and P. nigrolimbata Mello-Leitao, 1941 is considered its junior subjective synonym. Brachylibitia Mello-Leitao, 1941, is herein considered a junior subjective synonym of Platymessa and its type species, Brachylibitia ectroxantha Mello-Leitao, 1941, considered a species inquirenda, forming the new combination Platymessa ectroxantha. Genital morphology of Platymessa h-inscriptum is described and some characters are discussed regarding their importance in cosmetid taxonomy. Novel forms of sexual dimorphism are described in coxa IV. PMID- 27394289 TI - Five new, microendemic Asian Leaf-litter Frogs (Leptolalax) from the southern Annamite mountains, Vietnam. AB - The Leptolalax applebyi group of Asian leaf-litter frogs currently comprises four species of particularly small-bodied (<40 mm SVL) species distributed in the Central Highlands of Vietnam and northeastern Cambodia. In addition to their small size, the group is characterized by their morphological and genetic similarities, as well as their breeding habitat at headwaters of small mountain streams and seeps. A recent study suggested that at least two-thirds of the diversity of the group remained hidden within morphologically cryptic lineages. We expand upon the molecular, morphometric, and acoustic data and formally delineate and describe five of these lineages as distinct species: Leptolalax ardens sp. nov., Leptolalax kalonensis sp. nov., Leptolalax pallidus sp. nov., Leptolalax maculosus sp. nov., and Leptolalax tadungensis sp. nov. Due to habitat loss, the current ranges of these species are likely to be a fraction of their historical extent and under continued threat from deforestation. PMID- 27394290 TI - Three new South American species of genus Aphis (Hemiptera: Aphididae)
living on species of Euphorbia (Euphorbiaceae). AB - Three species of Aphis living on species of Euphorbia in Argentina and Chile are described: Aphis tehuelchis Nieto Nafria & Lopez Ciruelos, sp. n., from viviparous females collected in the Argentinean provinces of Santa Cruz and Neuquen, Aphis maulensis Mier Durante & Garcia-Tejero, sp. n., from viviparous females collected in the Chilean Region VII, and Aphis eucollinae Lopez Ciruelos & Ortego, sp. n., from viviparous females, oviparous females and males collected in the Argentinean province of Mendoza. These new species may be distinguished from each other, besides other features, by the abdominal marginal tubercles: in A. tehuelchis these are present on segments 1 and 7 and on several of segments 2 to 6, in A. maulensis they are on segment 1 and on several segments 2 to 6, but lacking on segment 7, and in A. eucollinae they are only on segments 1 and 7. Differences between the new species and those currently known living on Euphorbia around the world are presented. PMID- 27394291 TI - A new species of the thorid genus Paralebbeus Bruce & Chace, 1986 (Crustacea: Decapoda: Caridea) from the deep sea of the Northwestern Pacific Ocean. AB - During recent dives by the Chinese manned submersible "Jiaolong", some shrimp specimens were sampled from the deep sea of the Northwestern Pacific Ocean. A new species of the caridean family Thoridae, Paralebbeus jiaolongi sp. nov., is described and illustrated in this study. The rostrum armed with only one subterminal ventral tooth can easily distinguish the new species from its congeners. PMID- 27394292 TI - Protosclerogibba australis gen. et sp. nov., new genus and species of sclerogibbid wasps (Hymenoptera: Sclerogibbidae) from South Africa. AB - Protosclerogibba australis Olmi, Marletta, Guglielmino & Speranza, gen. et sp. nov. is described and illustrated from specimens collected in Kimberley (Northern Cape Province, South Africa). The female of the new taxon is the first micropterous sclerogibbid. Females of other extant Sclerogibbidae are always apterous, whereas fossil females can be apterous or macropterous. PMID- 27394293 TI - Two new species of Lamiinae (Coleoptera: Cerambycidae) from the Neotropical Region. AB - Two new species of Cerambycidae are described from the Neotropical Region: Estoloderces obliquus sp. nov. from Costa Rica and Stereomerus swifti sp. nov. from Ecuador. PMID- 27394294 TI - Rallus nanus nomen novum: a replacement name for Rallus minutus Alcover et al. 2015. AB - In a recent paper, we described five new species of rails from the Macaronesian islands (Alcover et al., 2015). We proposed the name of Rallus minutus to designate the Sao Jorge rail. One day after its publication, Fred Ruhe (via e mail) pointed out to us that the name was preoccupied, making Rallus minutus Alcover, Pieper, Pereira & Rando 2015 a primary homonym, which in turn makes it permanently invalid. PMID- 27394295 TI - A new species of Lamprodila (Ovalisia Kerremans, 1900) (Coleoptera: Buprestidae) from Sulawesi, Indonesia. AB - There have been a number of fairly recent papers dealing with Ovalisia Kerremans, 1900 under different generic or subgeneric names: Bily (1993, as Pagdeniella Thery, 1935; 1997, as Ovalisia), Bily et al. (2009, as Lamprodila (Ovalisia), Holynski (2000, 2011a, 2011b, as Ovalisia). Holynski (2011a, 2011b) has a number of misgivings over using the name Lamprodila Motschulsky 1860 for the genus containing the subgenus Ovalisia Kerremans, however as there does not appear to be any objective way to confirm or refute Holynski's views concerning Motschulsky's intentions when he coined the name Lamprodila, I choose to follow the recent catalogues of Kuban 2006 and Bellamy 2008 who treat Ovalisia Kerremans, 1900 as a subgenus of Lamprodila. PMID- 27394296 TI - First species of Tinaroo Chandler from outside Australia (Coleoptera: Staphylinidae: Pselaphinae). AB - As a result of Chandler's recent generic revision of the Australian Pselaphinae (Chandler 2001), eleven genera of the tribe Batrisini are currently known to occur in Australia. Seven of them (Amblybatrisus Chandler, Daintree Chandler, Gadgarra Chandler, Mossman Chandler, Neurum Chandler, Spurgeon Chandler, and Tinaroo Chandler) are so far endemic, and four genera (Ancistromus Jeannel, Batrisocenus Raffray, Coryphomodes Jeannel, and Hypochraeus Raffray) also occur in the Oriental region. PMID- 27394297 TI - Australian Marsh Beetles (Coleoptera: Scirtidae). 9. The relations of Australasian Ypsiloncyphon species to their Asian congeners, additions, mainly to Petrocyphon and Prionocyphon, and a key to Australian genera of Scirtinae. AB - The endemic Australasian species of Ypsiloncyphon are the sister group of the combined Asian species groups 1, 2, and 4. The description of the type species, Y. chlorizans (Klausnitzer), is supplemented by details of male and female genitalia. New species are described and illustrated in several genera: Austrocyphon scissus n. sp., Leptocyphon abnormis n. sp., Petrocyphon bonang n. sp., P. lacteus n. sp., P. televisionarius n. sp., Prionocyphon bidentatus n. sp., P. cacatua n. sp., P. laurae n. sp., P. neboissi n. sp., P. serratus n. sp., P. uncatus n. sp., and P. urbanus n. sp. Genus Prionocyphon is distinguished from Oriental genera with similar antennal modifications. However, a synapomorphy of Prionocyphon as presently understood is not known. Supplementary information on various species in the aforementioned genera and in Pachycyphon and Calvarium is provided. A key to the genera of adult Australian Scirtidae: Scirtinae is presented. PMID- 27394298 TI - Descriptions of three new species of Strattis Pascoe, 1883 (Coleoptera:
Curculionidae: Cryptorhynchinae) from the Indian subcontinent. AB - The cryptorhynchine genus Strattis Pascoe originally described from Sri Lanka is recorded from India with the descriptions of three new species: S. pascoei sp. nov., S. maculatus sp. nov., and S. srilankaiensis sp. nov. from the Indian subcontinent. Strattis biguttatus is designated as type species for the genus. A key to species is provided. The character of a presumable stridulatory structure between the meta-femur and the first abdominal ventrite is discussed. PMID- 27394299 TI - A new species of the genus Pachytriton (Caudata: Salamandridae) from Hunan and Guangxi, southeastern China. AB - Despite recent descriptions of multiple new species of the genus Pachytriton (Salamandridae), species richness in this China-endemic newts genus likely remains underestimated. In this study, we describe a new species of Pachytriton from northeastern Guangxi and southern Hunan, southeastern China. Both molecular analyses and morphological characters reveal that the new species can be distinguished from its congeners. The mitochondrial gene tree identified the new lineage highly divergent (uncorrected p-distance > 5.8 % by mitochondrial gene) from currently recognized species and placed it as the sister species of P. xanthospilos and P. changi. Furthermore, a nuclear gene haplotype network revealed a unique haplotype in the new populations. Statistical species delimitation using Bayes factor strongly supported the evolutionary independence of the new species from the closely-related P. xanthospilos. Morphologically, the new species is characterized by a uniformly dark brown dorsum without bright orange dots or black spots; irregular orange blotches on the venter; tips of fingers and toes orange on the dorsal side; moderately developed webs on the side of digits; absence of costal grooves between the axilla and groin; and widely open vomerine tooth series. PMID- 27394300 TI - New data on the taxonomy and distribution of ten Neotropical chewing lice of the genus Myrsidea (Phthiraptera: Menoponidae), including the description of a new species. AB - The new species Myrsidea alexanderi is described and illustrated ex Pheugopedius maculipectus (Troglodytidae) from Honduras. Redescriptions and illustrations are given for both sexes of Myrsidea chiapensis ex Calocitta formosa from Costa Rica, and the male of M. dissimilis ex Progne chalybea from Brazil. Also, seven other previously known species or subspecies of the louse genus Myrsidea are recorded and discussed from passerine birds of the Neotropical Region, as follows: Myrsidea antiqua, Myrsidea balteri, Myrsidea diffusa, Myrsidea nesomimi borealis, Myrsidea paleno, Myrsidea psittaci and Myrsidea serini. Our data increase knowledge of intraspecific morphological variability within these species, and also of their host and geographical distribution. New host-louse associations are: Agelaioides badius for M. psittaci; Basileuterus culicivorus and Myiothlypis leucoblephara for M. paleno; Mimus saturninus for M. nesomimi borealis; and Icterus dominicensis and Molothrus rufoaxillaris for Myrsidea sp. PMID- 27394301 TI - Four new species of the spider genus Nesticella Lehtinen & Saaristo, 1980 from Laos, Thailand and Myanmar and the first description of the male of Nesticella yui Wunderlich & Song, 1995 with a proposed new diagnostic character for the family Nesticidae Simon, 1894 (Arachnida, Araneae). AB - During various expeditions to Laos between 2003 and 2012 and one expedition to Myanmar in 2014, spiders of the family Nesticidae were collected inside and outside of caves. This was the first time this family was encountered in Laos. All specimens belong to the genus Nesticella Lehtinen & Saaristo, 1980. Four species have been recognized as being new to science, which are described in this paper: Nesticella beccus n. sp. (male, female; LAOS: Bolikhamsay Province, Luang Prabang Province, Huaphan Province, Khammouan Province, THAILAND: Mae Hong Son Province), Nesticella laotica n. sp. (male, female; LAOS: Vientiane Province, Huaphan Province, Luang Prabang Province, Bolikhamsay Province), Nesticella foelixi n. sp. (male; LAOS: Bolikhamsay Province) and Nesticella michaliki n. sp. (male, female; MYANMAR: Chin State). The male of Nesticella yui Wunderlich & Song, 1995 is described for the first time and it is the first record for Laos. Results from a first micro-computed tomography analysis of a female copulatory organ for this genus are provided. This analysis proves that female Nesticella exhibit a complex functional receptaculum, which is highly complex within the genus. The presence of a special type of leg setae (pipette setae) in males is proposed as diagnostic for the family Nesticidae. PMID- 27394302 TI - Key to species of the genus Bambusananus Li & Xing (Hemiptera: Cicadellidae: Deltocephalinae), and with description of a new species from China. AB - A new species, Bambusananus bispinosus sp. nov., is described and illustrated from Yunnan Province, China. A key based on the aedeagus is given to distinguish all species of the genus. The type specimens of the new species are deposited in the Institute of Entomology, Guizhou University, Guiyang, China (GUGC). PMID- 27394303 TI - Two new species of the Rhyacophila anatina Species Group from China (Trichoptera: Rhyacophilidae). AB - Two new species of the Rhyacophila anatina Species Group, R. coalita n. sp. and R. bicaudata n. sp. are described, diagnosed and illustrated. Rhyacophila coalita n. sp. is somewhat similar to R. yipung Schmid and R. elongata Kimmins in the male genitalia, but can be distinguished from them by the deep incision at the apex of the dorsal process of the aedeagus, fused anal sclerites, and a pair of membranous bulbs at the middle of the aedeagus. Rhyacophila bicaudata n. sp. is similar to R. triangularis Schmid in male genitalia, but can be diagnosed by the longer preanal appendages, the slightly incised posteroventral margins of preanal appendages, and a gradually narrowed apicodorsal lobe of segment IX. PMID- 27394304 TI - Laimosemion leticia (Teleostei: Cyprinodontiformes: Rivulidae), a new species from the upper Rio Amazonas, Southern Colombia. AB - Laimosemion leticia is described from the Rio Tacana drainage, upper Rio Amazonas basin, Southern Colombia. The new species was found in a shallow swamp within a tropical rainforest in the vicinity of Leticia, capital of the department of Amazonas and southernmost municipality of Colombia. This miniature species is considered to be a member of the Owiyeye subgenus, which is diagnosed by a unique frontal squamation. Laimosemion leticia can be distinguished from all other species of the genus by the unique colour pattern on the unpaired fins. The new species appears related to L. jauaperi, L. uatuman and L. ubim due to the similar flank colour pattern in males, but is easy distinguished by coloration of the unpaired fins and morphological characters. PMID- 27394305 TI - Description of three new species of Encyrtidae Walker (Hymenoptera: Chalcidoidea) from India. AB - Three new species of Encyrtidae are described from material collected from the states of Karnataka and Tamil Nadu, India-Bureshiella antennata sp. nov., Proleurocerus montanus sp. nov. and Pseudectroma annamalaicus sp. nov. Keys to the species of all the three genera are provided and Bureshiella Hoffer is reported for the first time from India. PMID- 27394306 TI - A new species of the genus Hyalessa (Hemiptera, Cicadidae) from China, with DNA barcoding data and a key to related species. AB - One new species of the genus Hyalessa China, H. wangi sp. nov., from Yunnan, China is described. Partial mitochondrial COI gene (DNA barcoding) of this new species is sequenced and uploaded to GenBank. A key to all species of Hyalessa is provided. PMID- 27394307 TI - Species discovery and diversity in Lobocriconema (Criconematidae: Nematoda) and related plant-parasitic nematodes from North American ecoregions. AB - There are many nematode species that, following formal description, are seldom mentioned again in the scientific literature. Lobocriconema thornei and L. incrassatum are two such species, described from North American forests, respectively 37 and 49 years ago. In the course of a 3-year nematode biodiversity survey of North American ecoregions, specimens resembling Lobocriconema species appeared in soil samples from both grassland and forested sites. Using a combination of molecular and morphological analyses, together with a set of species delimitation approaches, we have expanded the known range of these species, added to the species descriptions, and discovered a related group of species that form a monophyletic group with the two described species. In this study, 148 specimens potentially belonging to the genus Lobocriconema were isolated from soil, individually measured, digitally imaged, and DNA barcoded using a 721 bp region of cytochrome oxidase subunit 1 (COI). One-third of the specimens were also analyzed using amplified DNA from the 3' region of the small subunit ribosomal RNA gene (18SrDNA) and the adjacent first internal transcribed spacer (ITS1). Eighteen mitochondrial haplotype groups, falling into four major clades, were identified by well-supported nodes in Bayesian and maximum likelihood trees and recognized as distinct lineages by species delimitation metrics. Discriminant function analysis of a set of morphological characters indicated that the major clades in the dataset possessed a strong morphological signal that decreased in comparisons of haplotype groups within clades. Evidence of biogeographic and phylogeographic patterns was apparent in the dataset. COI haplotype diversity was high in the southern Appalachian Mountains and Gulf Coast states and lessened in northern temperate forests. Lobocriconema distribution suggests the existence of phylogeographic patterns associated with recolonization of formerly glaciated regions by eastern deciduous forest, but definitive glacial refugia for this group of plant parasitic nematodes have yet to be identified. Unlike agricultural pest species of plant-parasitic nematodes, there is little evidence of long-distance dispersal in Lobocriconema as revealed by haplotype distribution. Most haplotype groups were characterized by low levels of intragroup genetic variation and large genetic distances between haplotype groups. The localization of nematode haplotypes together with their characteristic plant communities could provide insight into the historical formation of these belowground biotic communities. PMID- 27394308 TI - Description of Basiria birjandiensis n. sp (Nematoda: Tylenchidae) from South Khorasan province with a checklist of the family Tylenchidae Orley 1880 from Iran. AB - In order to identify plant-parasitic nematodes (family Tylenchidae Orley 1880) associated with Ziziphus zizyphus in Iran, 360 soil and root samples were collected from South Khorasan province during 2012-2014. Herein, a new species of Basiria and several known members of the family Tylenchidae are reported. B. birjandiensis n. sp. is characterized by short body length (584-748 um [660.6+/ 72.3]), lip region with flat apex, stylet 11-12 um (11.3+/-0.5), excretory pore position varying from isthmus level to the middle of the basal bulb (78-91 um from the anterior end of the body), post-vulval uterine sac 8-14 um (10.7+/-1.9) long, filiform tail (151-181 um, c= 3.7-4.2, c'= 14.3-17.2) and body annuli 0.5-1 um (0.6+/-0.1) wide. A checklist of Tylenchidae species from Iran is also presented. PMID- 27394309 TI - Comparative morphology on the egg chorion characters of some Noctuidae (Lepidoptera). AB - A comparative morphological analysis is provided for 70 species belonging to 59 genera of 13 subfamilies of Noctuidae from Ukraine. Diagnostic characters of the eggs for some species are identified. A comparison with representatives from other families of Noctuoidea is conducted. Some characters typical for separate species and general characters typical for most species are discussed. PMID- 27394310 TI - Sinocatops gen. nov., an apterous genus of Cholevini (Coleoptera: Leiodidae: Cholevinae) from China, with emphasis on differences with allied Rybinskiella Reitter, 1906. AB - A new apterous genus (Sinocatops gen. nov.) with a single new species (S. ruzickai sp. nov.) of Cholevini, is described from Sichuan Province, China. It is compared in detail to allied Rybinskiella Reitter, 1906 with some selected but important morphological characters to show their differences presented in a table. Color plates are presented to illustrate important morphological characters of S. ruzickai sp. nov. and examined species of Rybinskiella. The taxonomic state of Rybinskiella is also briefly disscussed. PMID- 27394311 TI - New species, new records and re-description of spider mites (Acari: Tetranychidae) from India. AB - Two species of Tetranychidae (Acari), Oligonychus neotylus sp. nov. from Zea mays and Pennisetum purpureum (Poaceae) and Tetranychus hirsutus sp. nov. from Gymnema sylvestre R. Br. (Apocynaceae) are described from Karnataka state, south India. Tetranychus bambusae Wang and Ma is recorded for the first time from India and re described. Four other species are reported for the first time from India viz., Oligonychus coniferarum (McGregor), Oligonychus duncombei Meyer, Tetranychus marianae McGregor and Tetranychus okinawanus Ehara from Cupressus sp., an undetermined grass, Centrosema pubescens and Adenium obesum, respectively. PMID- 27394312 TI - Cestodes of the blue shark, Prionace glauca (Linnaeus 1758), (Carcharhiniformes: Carcharhinidae), off the west coast of Baja California Sur, Mexico. AB - The cestode species recovered from the spiral intestines of 27 blue sharks (Prionace glauca) (Linnaeus, 1758) are reported from the western coast of Baja California Sur (BCS). The sampling was undertaken on a monthly basis from January 2003 to January 2004. The helminthological examination indicated the presence of four species of cestodes: Platybothrium auriculatum Yamaguti, 1952; Prosobothrium japonicum Yamaguti, 1934; Anthobothrium caseyi (Yamaguti, 1934) Ruhnke & Caira, 2009; and Paraorygmatobothrium prionacis (Yamaguti, 1934) Ruhnke, 1994. Of all the 27 sharks examined, 88.8% were infected with at least one cestode species. The most frequent species was P. auriculatum infecting 85% of the spiral intestines examined. In contrast the species with the highest mean intensity was P. prionacis (80.4 200). The species richness of cestodes in P. glauca is very similar in other regions of the world despite its wide distribution; however, this richness is low compared with other species of sharks within the same family. The feeding and host-specific are important factors that influence the parameters of infection of cestodes in this shark. On the west coast of BCS, Prionace glauca feeds mainly on red crab Pleuroncodes planipes Stimpson, 1860; squids Gonatus californiensis Young, 1972, Ancistrocheirus lesueurii (D'Orbigny, 1842), Haliphron atlanticus Steenstrup, 1861, and low proportion of fish teleosts as Merluccius productus (Ayres, 1855), Sardinops sp. Hubbs, 1929 and Scomber japonicus Houttuyn, 1872. We speculate that these prey could be involved as the second intermediate hosts of these cestodes, as in other members of these genera, although the life cycles of none are known. PMID- 27394313 TI - A new species of Brasineura Silva-Neto & Garcia Aldrete (Psocodea, 'Psocoptera', Ptiloneuridae), with comments on morphological variation in B. troglophilica and a revised generic diagnosis. AB - Brasineura serranortensis sp. n. is here described and illustrated. This is the third known species of Brasineura and differs from the other species in the genus in phallosome, hypandrium and paraproct structure. Comments on variation in fore wing venation, and new records for B. troglophilica are included. A revised generic diagnosis is also presented. PMID- 27394314 TI - Aoteasalda and Kiwisaldula, two new genera of Saldidae (Hemiptera: Heteroptera), with a key to New Zealand genera and a new synonymy in Zemacrosaldula. AB - Aoteasalda new genus, is described with Saldula maculipennis Cobben, 1961, as type species, resulting in the following new combination Aoteasalda maculipennis (Cobben, 1961). Kiwisaldula new genus, is described with Saldula parvula Cobben, 1961, as type species. The following new combinations are made: Kiwisaldula parvula (Cobben, 1961); Kiwisaldula butleri (White, 1878); Kiwisaldula laelaps (White, 1878); Kiwisaldula stoneri (Drake & Hoberlandt, 1950). Two species are described as new: Kiwisaldula manawatawhi new species, Kiwisaldula porangahau new species. A lectotype is designated for Salda laelaps White, 1878. The holotype of Salda butleri White, 1878, and the type series of Saldula trivialis Cobben, 1961, and Saldula maculipennis Cobben, 1961, are documented. A new synonymy is established in the genus Zemacrosaldula (valid name listed after equal sign): Saldula trivialis Cobben, 1961 = Zemacrosaldula australis (White, 1876). A revision of the taxonomy of Aoteasalda and Kiwisaldula species occurring on New Zealand's North Island and nearby offshore islands, is presented. Morphological descriptions are provided, with illustrations emphasising the most significant diagnostic features of the external morphology and male genitalia. Information is given on synonymy, type data, material examined, geographic distribution, and biology. Species of Kiwisaldula and genera of Saldidae recognised for New Zealand, are keyed. PMID- 27394315 TI - A reassessment of Melanophidium Gunther, 1864 (Squamata: Serpentes:
Uropeltidae) from the Western Ghats of peninsular India, with the description of a new species. AB - A new species of the uropeltid snake genus, Melanophidium Gunther, 1864 is described based on a series of eight specimens. Melanophidium khairei sp. nov. is the fourth species described in the genus, and the first for 144 years. Superficially M. khairei sp. nov. resembles M. punctatum Beddome, 1871 in being piebald and punctate (and it was previously misidentified as M. punctatum), but in many scalation characters it more closely resembles M. wynaudense (Beddome, 1863). The new species occurs in southern Maharashtra, Goa, and northern Karnataka, in the Western Ghats region of peninsula India. It is the most northerly member of its genus. Lectotypes and paralectotypes are designated for M. wynaudense, M. bilineatum Beddome, 1870, and M. punctatum. A new key to the species of Melanophidium is presented. Aspects of the morphology, taxonomy and distribution of the three previously described species of Melanophidium are reviewed and revised. PMID- 27394316 TI - Revision of the genus Coeligetes from Malaysia and Indonesia, and description of Coeligetoides gen. nov. (Coleoptera: Chrysomelidae: Galerucinae). AB - The species of the genus Coeligetes Jacoby, 1884 distributed in Malaysia and Indonesia are revised, illustrated and keyed. New species, C. howardi sp. nov. from Borneo is described. New synonymy Coeligetes submetallica Jacoby, 1884 = C. wilcoxi Mohamedsaid, 1994 (syn. nov.) is proposed. New genus and species Coeligetoides trifurcatus gen. nov., sp. nov. (Malaysia, Brunei, Indonesia and Thailand) is described, illustrated and compared with related genera. PMID- 27394317 TI - Review of Cosmocomoidea (Hymenoptera: Mymaridae) from China, with descriptions of two new species. AB - Seven species of Cosmocomoidea Howard (Hymenoptera: Mymaridae) from China are keyed and illustrated. The two new species are C. rugosa Aishan, Triapitsyn & Xu sp. n. (Guangdong and Yunnan) and C. tenuis Xu, Lin & Hu sp. n. (Fujian). Three species are newly recorded from China, C. atra (Foerster) s.l., C. kikimora (Triapitsyn), and C. oxypygus (Foerster). PMID- 27394318 TI - Supplementary descriptive notes of the Sinella and Coecobrya (Collembola: Entomobryidae) species from North America, Hawaii and Japan. AB - Many known collembolan species lack sufficient descriptive details so that further taxonomical comparison cannot be achieved. When sorting documents and materials from Prof. Jian-Xiu CHEN, Nanjing University, we found many old but valuable drafts on Sinella and Coecobrya species from North America, Hawaii and Japan. Supplementary descriptions, particularly chaetotaxy, were provided for the following species: S. agna Christiansen & Bellinger, 1980, S. alata Christiansen, 1960, S. baca Christiansen & Bellinger, 1980, S. barri Christiansen, 1960, S. hoffmani Wray, 1952, S. sexoculata (Schott, 1896), S. straminea (Folsom, 1899), S. yosiia Christiansen & Bellinger, 1992, C. akiyoshiana Yosii, 1956, C. borerae Christiansen & Bellinger, 1992, C. ishikawai Yosii, 1956, C. kukae Christiansen & Bellinger, 1992, C. lua Christiansen & Bellinger, 1992, C. nupa Christiansen & Bellinger, 1992, C. tibiotarsalis Yosii, 1964. Sinella cavernarum (Packard, 1888) was redescribed based on topotypes and more additional materials. PMID- 27394319 TI - Four new species of Epacanthion Wieser, 1953 (Nematoda: Thoracostomopsidae) in intertidal sediments of the Nanji Islands from the East China Sea. AB - Four new species of Epacanthion are described from intertidal sandy sediments in the Nanji Islands National Marine Natural Reserve from the East China Sea. Males of all four new species have short spicules (< 2 anal body diameter) and a characteristic cervical circle of distinctly short and densely arranged setae at the pharyngeal region: Epacanthion hirsutum sp. nov. with a cervical circle of a single row of setae posterior to the nerve ring; E. longicaudatum sp. nov. with a cervical circle of 16 bundles each composed of six setae in two longitudinal rows posterior to the nerve ring; E. fasciculatum sp. nov. with a cervical circle of 18 bundles each composed of about 10 setae posterior to the nerve ring; and E. sparsisetae sp. nov. with a cervical circle of eight bundles each composed of about 10 setae anterior to the nerve ring. Among the known species of Epacanthion, only two species possess these features: E. quadridisci and E. gorgonocephalum. Epacanthion quadridiscus has six bundles of setae situated at the same level of the nerve ring, while E. gorgonocephalum has distinctly dense setae forming a wide band at the pharyngeal region. Epacanthion hirsutum sp. nov. differs from all congeners by the cervical circle composed of a single row of setae. Epacanthion sparsisetae sp. nov. is unique in having the cervical circle of bundles anterior to the nerve ring. Epacanthion longicaudatum sp. nov. differs from E. fasciculatum sp. nov. by the body size and the structure of the cervical circle. An updated diagnostic key to 28 valid species of Epacanthion is proposed. PMID- 27394320 TI - New records of the East-Asian Nemoura species (Plecoptera: Nemouridae)
for South of the Russian Far East with description of the larvae. AB - Three species of the Nemoura, N. jejudoensis Zwick & Baumann, 2011 and N. jilinensis Zhu & Yang, 2003, and N. tripotini Zwick, 2010 are reported in the South of the Russian Far East for the first time. The larvae of the three species are described and illustrated. The larvae were associated with adults by rearing or by preemergent male larva. The main diagnostic features of the larvae are based on the differences in the chaetotaxy the pronotum, legs, abdominal, and cercal segments. PMID- 27394321 TI - A world catalogue of Phragmataecia (Lepidoptera: Cossidae), with a new species from Kazakhstan and Kyrgyzstan. AB - Phragmataecia valikhanovi Yakovlev & Witt sp. nov. is described from Kazakhstan and Kyrgyzstan. The Catalogue of the Genus Phragmataecia Newman, 1850 is provided. PMID- 27394322 TI - Taxonomic revision of Coniceromyia Borgmeier (Diptera: Phoridae), with the description of three new species from Brazil. AB - The 55 known species of Coniceromyia are herein revised. Three new species from the Atlantic Forest in Brazil are described-C. apioneura, sp.nov., C. neofusca, sp.nov. and C. tanycrossa, sp.nov.-and fourteen species are redescribed. Most of the species have foreleg, wing, hind femur, and male terminalia illustrated. Characters previously unnoticed are described for the first time. Coniceromyia cubensis Brues, previously accepted as a synonym of C. latimana (Malloch), has its status reinstated. Taxonomic problems in the genus are addressed, including the condition of the damaged holotypes of C. boliviana Borgmeier and C. vespertilio Schmitz, and our inability to associate males with the female holotypes of C. arizonensis Borgmeier, C. fusca Borgmeier and C. grenadensis (Brues). The holotypes of Coniceromyia angularis Borgmeier & Prado and Coniceromyia laticosta Prado are considered to be lost. PMID- 27394323 TI - Revision of the Genus Physiphora Fallen 1810 (Diptera: Ulidiidae: Ulidiinae). AB - The genus Physiphora includes at least 29 species, most of them occurring predominantly in the Afrotropical Region and a few species native to the other regions of the Old World. At least P. alceae (Preyssler 1791) and P. clausa (Macquart 1843) are subcosmopolitan species unintentionally introduced into the Australasian, Nearctic, and Neotropical Regions. Twelve new species from the Afrotropical Region are described: P. hendeli sp. n., P. igniceps sp. n., P. kirki sp. n., P. maraisi sp. n., P. meyi sp. n., P. opalizana sp. n., P. orinigra sp. n., P. polita sp. n., P. rugosa sp. n., P. spriggsi sp. n., P. steyskali sp. n., and P. virens sp. n. Detailed illustrated descriptions and a key for identification are provided for all the species of Physiphora. Analysis of the new and previously known biological data shows that larvae of most Physiphora species are saprophagous associated with rotting tissues of palms (apparently infested by the palm weevils), giant Euphorbia, and even baobabs and poplars. Some species are attracted to (and as larvae possibly can develop in) the dung of ungulates. The following synonymy is established: Physiphora clausa (Macquart 1843) = Physiphora hainanensis Chen in Chen & Kameneva 2007: 24, syn. n.; Physiphora flavipes (Karsch 1888) = Chrysomyza africana Hendel 1909, syn. n., = Cliochloria senegalensis Enderlein 1927, syn. n. PMID- 27394324 TI - The ant genus Polyrhachis F. Smith in sub-Saharan Africa, with descriptions of ten new species. (Hymenoptera: Formicidae). AB - Ten new sub-Saharan species of the ant genus Polyrhachis are described: P. gibbula n. sp. and P. omissa n. sp. belonging in the viscosa-group; P. brevipilosa n. sp., P. dubia n. sp., P. longiseta n. sp., P. luteipes n. sp., P. submarginata n. sp., and P. terminata n. sp. in the revoili-group; P. doudou n. sp. and P. fisheri n. sp. in the militaris-group. Also, P. epinotalis Santschi and P. kohli Forel are revived from synonymy with P. militaris (Fabr.) and P. volkarti Forel respectively. The type of P. cubaensis Mayr is described, changing the interpretation of the taxon and revalidating two of its synonyms, P. gerstaeckeri Forel and P. wilmsi Forel stat. n.. The examination of the type of Polyrhachis revoili Andre has proved this taxon to be different from previous interpretations; its position is reviewed and all of its synonyms are transferred to P. weissi Santschi. In addition, the first description of the worker of P. andrei Emery is provided, as well as some new records and taxonomic and morphological notes concerning other species. Finally, a synonymic list of the 61 currently known sub-Saharan species, a key to species-groups and an updated key to the workers are given. PMID- 27394325 TI - Genus Neelus Folsom, 1896 (Hexapoda, Collembola) reveals its diversity in cave habitats: two new species from Croatia. AB - Two new species of the genus Neelus Folsom, 1896, N. cvitanovici sp. nov. and N. lackovici sp. nov., are described from caves of Croatia. N. lackovici sp. nov. exhibit marked troglomorphic features such as extremely elongated ungua and antennae, larger body among others. Descriptions are completed with comparative tables for chaetotaxy of antennae and legs. Diagnostic table for the congeners and identification key to the world species are provided. Distribution records of other Neelus species in Croatian caves are added. Threats of troglobiotic Neelus species in Croatia are discussed. PMID- 27394326 TI - Thamnocephalus chacosaltensis, a new species of Anostraca (Crustacea: Branchiopoda) from Salta province (Argentina). AB - Thamnocephalus chacosaltensis, a new species of fairy shrimp, was found in a temporary turbid pond in the Rivadavia Department, Salta province, Argentina (24o13'19.3''S; 62o 52'14.3''W), belonging to the Chaco salteno. The males present a well developed frontal appendage. Their First (FB) and Third (TB) branches show features diagnostic for the species. FB shows three sub-branches; the most proximal one is coiled, lacks spines all along, gradually thins in distal direction and flattens in the distal half; distally, the flattened portion is folded and ends blunt, bearing a small spine at the tip. TB is a broad-based triangular, thin, much flattened and folded outgrowth, with a small spine at the apex. Male genital and abdominal segments lack medio-ventral spines near their posterior margins. Comparisons with the other species of the genus are established. PMID- 27394327 TI - Checklist of leaf beetles (Coleoptera: Chrysomelidae) from the state of Morelos, Mexico. AB - We record 116 genera and 366 species of Chrysomelidae from the state of Morelos, Mexico. This represents an increase of 9.3% in the species richness of these beetles for the state. Also, Morelos is currently the third most diverse state in leaf beetles within Mexico, with 16.78% of total species recorded for the country. The most diverse genera were Calligrapha, Disonycha, Blepharida, Leptinotarsa, Cryptocephalus, Systena, Alagoasa, Diabrotica and Pachybrachis, each with more than eight species. Most of these genera contain large, showy beetles. When the chrysomelid fauna is more fully understood, some of the genera of tiny beetles will likely prove to be more diverse. PMID- 27394328 TI - Isotomidae (Collembola) of Buryat Republic. III. The genera Vertagopus and Agrenia, with a note on 'Claw index'. AB - Two genera are revised based on material from Buryatia (Russia, East Siberia). Vertagopus ceratus sp. nov. and V. asiaticus sp. nov. are described of which the former species is strictly alpine and is defined by pale colouration, the presence of chaetae on the anterior side of the ventral tube, and abundant sensillar chaetotaxy. V. asiaticus sp. nov. is widely distributed in Asia and is unusual due to only 9 chaetae in apical whorl on tibiotarsi. A key to species of Vertagopus Borner, recorded in the republic is given, and notes on morphology, distribution, and ecology are provided. In the genus Agrenia Borner, a form similar with A. bidenticulata was recorded in mountainous areas. Buryatian populations considerably differ from the diagnosis of the typical arctic A.bidenticulata (Tullberg) by a much longer claw. A conception of A. bidenticulata sensu lato complex is temporarily proposed basing on available materials from Palearctic, including High Arctic, sub-Arctic and South Siberian mountains. The complex consists of several local forms which are different in Claw index and associated Tibiotarsus/Claw ratio, while the dependence of the two indexes on the latitude is shown. PMID- 27394329 TI - A new species of the genus Discolaimus Cobb, 1913 (Nematoda: Dorylaimida: Qudsianematidae) from Qinghai, China. AB - A new species of the family Qudsianematidae Jairajpuri, 1965 collected from soil from Qinghai Province, China is described as Discolaimus anemaqen n. sp. It is mainly characterized by having a disc-like lip region with six labial sectors separated by six Y-shaped radial grooves; amphid fovea an inverted-stirrup shape; odontostyle aperture 53-59% of its length; anterior part of pharynx with two swellings, basal part expanded gradually with a sheath of tissue visible ventrally and at the base; no groups of large cells observed in cardiac region; female genital system amphidelphic; tail dorsally convex, conoid, with flat ventral side and bluntly rounded terminus, and males not found. The new species is close to D. major Thorne, 1939, D. similis Thorne, 1939 and D. silvicolus Sauer & Annells, 1985 in most measurements, but can be differentiated from them by lip morphology, pharynx structure, body size, and tail shape. A key to the species of Discolaimus is also provided. PMID- 27394330 TI - New Canadian records of Nemastoma bimaculatum (Fabricius), and a brief summary of introduced Eurasian harvestmen in North America (Arachnida, Opiliones). AB - Eurasian harvestmen have been introduced to, and have established themselves in North America. Species known to have been introduced include Trogulus tricarinatus (L.) 1767, Paroligolophus agrestis (Meade) 1855, Rilaena triangularis (Herbst) 1799, Oligolophus tridens (C. L. Koch) 1836, and Nemastoma bimaculatum (Fabricius) 1775, for the last of which new Canadian records (Ontario) are given below. It is not entirely determined if the species Phalangium opilio (L.) 1758, Opilio parietinus (DeGeer) 1778 and Mitopus morio (Fabricius) 1779 are introduced to North America, or are naturally of Holarctic distribution. The former seems the more likely hypothesis for the first two, but M. morio in North America may be native or may not be that species. Detailed descriptions and illustrations of all these species may be found in Martens (1978). PMID- 27394331 TI - Two new species of Scirtothrips genus-group (Thripidae) of Northern Peninsular Malaysia. AB - The survey of Thysanoptera in peninsular Malaysia has been concentrated largely in areas growing crops and flowers around Kuala Lumpur, and the Cameron Highlands, and there are few records of these insects from native forests particularly in the northern part of the country. The two species described here were collected during a recent visit to Belum-Temengor Forest Complex, in Perak State, part of the second largest forested area on the peninsular, and connected to the Bang Lang National Park, in Yala Province, Thailand. This forest has been well known as home to a number of endangered animals, including Malayan tigers and Asian elephants, as well as remarkable plant species such as Rafflesia with the world's largest flowers (Abdullah et al. 2011). Despite this, forest areas are facing a major challenge from the insatiable demand for timber, palm oil and minerals, with an 80% increase in deforestation rate in Malaysia between 1990 and 2005 (FAO 2010). Forested land in peninsular Malaysia has been estimated at 5.88 million-ha or 44% of total area, but the coverage of reserved virgin forest is about 0.40 % or 23,002-ha (Dahlan 2008). PMID- 27394332 TI - New species of Ribesaptera Heiss from eastern Madagascar (Hemiptera: Heteroptera: Aradidae). AB - The rich flat bug fauna of Madagascar comprises eleven apterous genera of Mezirinae with 21 species (Heiss 2012, Heiss & Marchal 2012) to date, and all of them are endemic: Ambohitantelya Heiss & Banar 2013 (1 sp.); Antsirabenus Heiss 2008 (2 spp.); Cervinotaptera Heiss & Marchal 2012 (1 sp.); Chlonocoris Usinger & Matsuda 1959 (3 spp.); Cimicomanes Kiritshenko 1959 (5 spp.); Classeyana Hoberlandt 1963 (1 sp.); Paulianum Hoberlandt 1957 (1 sp.); Pericartaptera Heiss 2009 (2 spp.); Ribesaptera Heiss 2011 (1 sp.); Robertiessa Hoberlandt 1963 (1 sp.) and Tananarivea Drake 1957 (3 spp.). PMID- 27394333 TI - Systematic revision of the marbled velvet geckos (Oedura marmorata species complex, Diplodactylidae) from the Australian arid and semi-arid zones. AB - Lizards restricted to rocky habitats often comprise numerous deeply divergent lineages, reflecting the disjunct nature of their preferred habitat and the capacity of rocky habitats to function as evolutionary refugia. Here we review the systematics and diversity of the predominantly saxicoline Australian marbled velvet geckos (genus Oedura) in the Australian arid and semi-arid zones using newly-gathered morphological data and previously published genetic data. Earlier work showed that four largely allopatric and genetically divergent lineages are present: Western (Pilbara and Gascoyne regions), Gulf (west and south of the Gulf of Carpentaria), Central (central ranges) and Eastern (Cooper and Darling Basins). None of these four populations are conspecific with true O. marmorata, a seperate species complex that is restricted to the Top End region of the Northern Territory. Top End forms share a short, bulbous tail whereas the other four lineages treated here possess a long, tapering tail. Morphological differences among the arid and semi-arid lineages include smaller body size, tapering lamellae and a shorter tail for the Gulf population, and a partially divided rostral scale in the Western population compared to the Central and Eastern populations. Accordingly, we resurrect O. cincta de Vis from synonymy for the Central and Eastern lineages, and regard this species as being comprised of two evolutionary significant units. We also describe the Gulf and Western lineages as new species: Oedura bella sp. nov. and O. fimbria sp. nov., respectively. We note that a predominantly arboreal lineage (the Eastern lineage of O. cincta) is more widely distributed than the other lineages and is phylogenetically nested within a saxicoline clade, but tends to have a deeper head and shorter limbs, consistent with morphological variation observed in other lizard radiations including both saxicoline and arboreal taxa. PMID- 27394334 TI - Four new species of Psechrus from Yunnan Province, China (Araneae, Psechridae). AB - Four new species of Psechrus are described from Yunnan Province: P. changminae sp. nov., P. conicus sp. nov., P. discoideus sp. nov. and P. spatulatus sp. nov. Herewith the number of species belonging to Psechrus in Yunnan Province extended from five to nine. Illustrations and colour photos are provided, with comparison of intraspecific variation of copulatory organs. PMID- 27394335 TI - A review of the genus Atrovirensis Kononenko, 2001 with description of four new species from China (Lepidoptera, Noctuidae: Xyleninae, Apameini). AB - The genus Atrovirensis Kononenko, 2001 is reviewed. Four new species (Atrovirensis parannamita sp. n., Atrovirensis furcatus sp. n., Atrovirensis sacculatus sp. n. and Atrovirensis miraculosus sp. n.) are described from China. A new combination Atrovirensis euplexina (Draudt, 1950), comb. n. [Valeria] is proposed. Two taxa of uncertain status (Atrovirensis sp. cf. parannamita and Atrovirensis sp. cf. furcatus) are included to the review. The updated checklist of the genus is presented. All taxa of the genus Atrovirensis are illustrated in colour with black and white photographs of their genitalia in 48 figures. PMID- 27394336 TI - Two new species of Bungona Harker, 1957 (Ephemeroptera: Baetidae) from Borneo, Indonesia. AB - Two new species of Bungona, belonging to the subgenera Chopralla Waltz & McCafferty, 1987 and Centroptella Braasch & Soldan, 1980, are described based on larvae from Kalimantan (Borneo, Indonesia). Bungona (Centroptella) papilionodes n. sp. is the third species described for the subgenus. It can be distinguished from Bungona (Centroptella) longisetosa (Braasch & Soldan, 1980) and Bungona (Centroptella) soldani (Muller-Liebenau, 1983) by the length of the maxillary palp, the presence or absence of an additional small denticle on the lateral margin of the distal incisor, and the spination of the paraproct. This new report of the subgenus greatly increases its geographic range of distribution, as it was known only from Sri-Lanka and China. Bungona (Chopralla) bintang n. sp. is the seventh species described for the subgenus Chopralla and the second described from Borneo. It differs from others species of the subgenus and especially from Bungona (Chopralla) pusilla (Muller-Liebenau, 1984) (Borneo) by the combination of lacking hindwing pads, the particular spination of distal margins of tergites, and the shape of the maxillary palp. The two new species fit into the recently revised concepts of Chopralla and Centroptella and confirm the characters used to support these taxa as valid subgenera. PMID- 27394337 TI - Studies on idiocerine leafhoppers with descriptions of Chinaocerus gen. nov. and three new species from China (Hemiptera: Cicadomorpha: Cicadellidae). AB - A new leafhopper genus of the tribe Idiocerini (Hemiptera: Cicadomorpha: Cicadellidae), Chinaocerus, is described from the southwest China together with three new species, C. kangdingensis Zhang & Li sp. nov. (Sichuan Province), C. bispinatus Zhang & Li sp. nov. (Yunnan Province) and C. shii Zhang & Li sp. nov. (Sichuan Province). Descriptions and illustrations of these three new species are provided, and a key for their separation is also given. PMID- 27394338 TI - Redefinition and revision of African Cosmetra Diakonoff, 1977 (Lepidoptera: Tortricidae) with description of six new species. AB - The eight species of Cosmetra Diakonoff present in mainland Africa are described and illustrated. Six new species are described: Cosmetra larseni, new species; C. fibigeri, new species; C. truncana, new species; C. multidentana, new species; C. usambarensis, new species; and C. juu; new species. Cosmetra neka Razowski & Brown is a junior synonym of Cosmetra tumulata (Meyrick), and C. mucronata Razowski & Wojtusiak is a junior synonym of C. spiculifera (Meyrick). PMID- 27394339 TI - Taxonomy of the Proisotoma complex. VI. Mobile forms of Proisotoma s.str. with the description of a new species from East Siberia (Collembola: Isotomidae). AB - Phenotypic dimorphism of four species of the genus Proisotoma s.str. is described. The modified specimens are characterized by protruding corneas of eyes, stronger pigmentation, enlarged and more chitinized furca, and extension of clavate tenent hairs in the distal part of the tibiotarsi. The characteristics of the modified specimens indicate higher mobile activity. Both sexes are affected by the dimorphism, with the "mobile" forms mostly co-occuring during the cold season with normal specimens. Proisotoma dualis sp. nov. is described from Buryat Republic. PMID- 27394340 TI - Stage description, new combination and new records of Neotropical Brachycercinae (Ephemeroptera: Caenidae). AB - We present taxonomic contributions and new records for Neotropical Brachycercinae based on material from Brazil. We performed a phylogenetic analysis in order to test the relationship between Alloretochus Sun & McCafferty, 2008 and Latineosus Sun & Mc- Cafferty, 2008, and Alloretochus sigillatus was recovered in the Latineosus clade. Therefore, we propose a new combination, Latineosus sigillatus comb. n. The nymph of Latineosus sigillatus is described and is associated with imago through molecular tools. Moreover, Alloretochus peruanicus (Soldan, 1986) is reported for the first time from Brazil. PMID- 27394341 TI - A new species of Thyreophagus (Acari: Acaridae) from Brazil, with notes on species associated with stored food and human habitats and a key to species of this genus. AB - A new species Thyreophagus cracentiseta n. sp. is described morphologically based on adult females, adult homeomorphic and heteromorphic males collected from chicken feed in Brazil. The Thyreophagus species associated with stored food and human habitats are reviewed, and a key to separate species of this genus is provided. PMID- 27394342 TI - Rumen ciliates in Brazilian sheep (Ovis aries), with new records and redescription of Entodinium contractum (Entodiniomorphida: Ophryoscolecidae). AB - The species composition, prevalence, and average relative abundance of rumen ciliates were analyzed in 16 Brazilian sheep. 28 species of ciliates were identified belonging to 3 families: Isotrichidae, Ophryoscolecidae, and Parentodiniidae. Among these ciliates, Entodinium alces, Metadinium esalqum, and M. rotundatum were found for the first time in sheep, and other 12 species for the first time in Brazilian sheep. Different morphotypes of parentodiniid ciliates were identified in 7 of the 16 sheep analyzed and this is the second report of this family in ruminants. The species Entodinium contractum was redescribed based on the new data on the general morphological features; for the first time, we described the oral infraciliature, which in this species is of the Entodinium-type. In this species, it is noteworthy that the prominent vestibular polybrachykinety can be used as an important identifying characteristic. PMID- 27394343 TI - "Symmetrical" hermit crabs of the family Pylochelidae (Crustacea: Decapoda: Anomura) collected by the "BIOPAPUA" and "PAPUA NIUGINI" expeditions in the Papua New Guinea, with descriptions of two new species. AB - Collections made during the recent expeditions to Papua New Guinea ("BIOPAPUA", 2010; "PAPUA NIUGINI", 2012) yielded a total of 12 species from the "symmetrical" hermit crab family Pylochelidae, including two new to science: Bathycheles incisus (Forest, 1987), B. integer (Forest, 1987), Cheiroplatea laticauda Boas, 1926, C. pumicicola Forest, 1987, C. rotundioculus n. sp., Pylocheles mortensenii Boas, 1926, and Xylocheles macrops (Forest, 1987) (Pylochelinae); Parapylocheles scorpio (Alcock, 1894), Trizocheles manningi Forest, 1987, T. moosai Forest, 1987, T. sakaii Forest, 1987, and T. spinidigitus n. sp. (Trizochelinae). Affinities of the two new species are discussed. Parapylocheles scorpio, Trizocheles manningi and T. sakaii are recorded from the South Pacific for the first time. Revised identification keys to species of Cheiroplatea and Trizocheles are provided. PMID- 27394344 TI - A genus-level classification of the family Thraupidae (Class Aves: Order Passeriformes). AB - The tanagers (Thraupidae) are a major component of the Neotropical avifauna, and vary in plumage colors, behaviors, morphologies, and ecologies. Globally, they represent nearly 4% of all avian species and are the largest family of songbirds. However, many currently used tanager genera are not monophyletic, based on analyses of molecular data that have accumulated over the past 25 years. Current genus-level classifications of tanagers have not been revised according to newly documented relationships of tanagers for various reasons: 1) the lack of a comprehensive phylogeny, 2) reluctance to lump existing genera into larger groups, and 3) the lack of available names for newly defined smaller groups. Here, we present two alternative classifications based on a newly published comprehensive phylogeny of tanagers. One of these classifications uses existing generic names, but defines them broadly. The other, which we advocate and follow here, provides new generic names for more narrowly defined groups. Under the latter, we propose eleven new genera (Asemospiza, Islerothraupis, Maschalethraupis, Chrysocorypha, Kleinothraupis, Castanozoster, Ephippiospingus, Chionodacryon, Pseudosaltator, Poecilostreptus, Stilpnia), and resurrect several generic names to form monophyletic taxa. Either of these classifications would allow taxonomic authorities to reconcile classification with current understanding of tanager phylogenetic relationships. Having a more phylogenetically accurate classification for tanagers will facilitate the study and conservation of this important Neotropical radiation of songbirds. PMID- 27394345 TI - A new species of Tenuipalpus sensu stricto (Acari: Tenuipalpidae) from Brazil, with ontogeny and a key to the known species. AB - The Cerrado is the second largest Brazilian biome, and is considered to be a "hotspot" due the great concentration of endemic species and high rate of deforestation. Surveys of the mite fauna present in this biome have revealed a great number of new species. In this paper, we describe Tenuipalpus spinosaurus sp. nov. (Acari: Tenuipalpidae), a new species of Tenuipalpus sensu stricto, from adult females, deutonymphs, protonymphs, larvae and eggs, collected on Terminalia argentea (Combretaceae), from the Cerrado in Brazil. Females of this new species bear a prominent longitudinal crest on the opisthosoma. The ontogenetic changes in the idiosoma and leg chaetotaxy of all stages are presented. A key to the world species of Tenuipalpus sensu stricto is provided. PMID- 27394346 TI - A new species of the genus Leptolalax (Anura: Megophryidae) from Mt. Gaoligongshan of western Yunnan Province, China. AB - A new species of the genus Leptolalax is described from the Tengchong Section of Gaoligongshan National Nature Reserve, Tengchong County, Yunnan Province, China. The new species, Leptolalax tengchongensis sp. nov., can be distinguished from its congeners by a combination of the following characters: (1) small size (SVL 23.9-26.0 mm in males, 28.8-28.9 mm in females); (2) dorsal skin shagreened and scattered with fine, round reddish tubercles; (3) toes with rudimentary webbing and narrow lateral fringes; (4) tympanum distinctly discernible, almost entirely black; (5) ventrolateral glands indistinct; (6) flanks with several distinct and large dark blotches; (7) ventral surfaces white, scattered with distinct irregular dark speckling; (8) iris not bicolored, uniformly dark brown and scattered with minute, coppery reticulations throughout. To date, the new species has only been found at its type locality in evergreen broadleaf forests at elevations between 2000-2100 m. PMID- 27394347 TI - Redescription of Acanthicus hystrix Agassiz, 1829 (Siluriformes: Loricariidae), with comments on the systematics and distribution of the genus. AB - The genus Acanthicus is diagnosed from remaining Loricariidae genera by several characters, including the absence of adipose fin, pectoral-fin spine enlarged and the presence of small plates in abdomen region. Acanthicus currently comprises two valid species: A. hystrix and A. adonis. Acanthicus hystrix is distinguished from A. adonis, mostly by having body and fins dark brown to almost completely black background colored, without clear spots or dots (vs. dark brown color background with white spots covering body and fins) and presence of ochre to grey stripes in caudal fin (vs. stripes absent on caudal fin). The holotype of A. hystrix was destroyed during a bombing raid in the Second World War, no neotype was designed and the species is recognized by the illustration present in the original description, whose text is short, and uninformative. In the present contribution, specimens from several institutions were examined, revealing that the species is widespread in the Amazon, Tocantins-Araguaia and Orinoco basins, while A. adonis is restricted to the lower rio Tocantins. Herein, a redescription of Acanthicus hystrix is provided, with a comprehensive diagnosis of the genus and its species, along with a distribution map of the genus, a key to species identification, and brief comments on the systematics and distribution of the genus. PMID- 27394348 TI - A new Bent-toed Gecko (Squamata: Gekkonidae: Cyrtodactylus) from Phetchaburi Province, Thailand. AB - A new Bent-toed Gecko, Cyrtodactylus phetchaburiensis sp. nov. is described from the Tha Yang District of Phetchaburi Province, western Thailand. It is a medium sized Cyrtodactylus (SVL to at least 63.2 mm), with small, mostly keeled tubercles in 20 regular longitudinal rows on dorsum; 33 scales across mid-venter between lowest rows of flank tubercles; enlarged row of femoral scales present; five precloacal pores in male, femoral pores and precloacal groove absent; 5-6 broad basal lamellae and 11 narrow distal lamellae beneath digit IV of pes; and a single median row of transversely enlarged subcaudal scales present. It has a dorsal colour pattern of large, dark, diffusely-edged markings on a fawn background and a pair of dark scapular patches. The species is a member of the Central Indochinese (Thai-Myanmar) clade of Cyrtodactylus and is most closely related to C. oldhami (Theobald), from which it differs in colour pattern. PMID- 27394349 TI - The genus Pachyseius Berlese, 1910 in Iran (Acari: Pachylaelapidae). AB - A new pachylaelapid mite Pachyseius persicus Babaeian & Masan sp. nov. is described and illustrated, based on adult females collected from litter and soil detritus of forest habitat in Northern Iran (Mazandaran Province). The new species can be easily distinguished from the other congeners by the following female character states: (1) presternal shields absent; (2) sternal shield coarsely punctate-reticulate over entire surface; (3) ventrianal shield with four pairs of pre-anal setae; (4) post-stigmatic section of peritrematal shields terminally rounded, reaching slightly beyond the coxae IV; (5) exopodal shields II-III free, exopodal shields III-IV fused to posterior section of peritrematal shields; (6) idiosoma with 11 pairs of setae in soft integument; (7) trochanter I with five setae, tarsus II with three spur-like setae, tarsus IV with 17 setae. Two species of Pachyseius previously reported from Iran, namely Pachyseius angustus Hyatt, 1956 and Pachyseius humeralis Berlese, 1910, are reviewed and discussed, respectively, and both records are considered to be based on misidentifications. PMID- 27394350 TI - Catalogue of type materials of springtails (Hexapoda, Collembola) in the Canadian National Collection of Insects, Arachnids & Nematodes. AB - The catalogue assembles and updates all data concerning the type material of Collembola kept in the Canadian National Collection of Insects, Arachnids & Nematodes in Ottawa (CNC). Information is provided for type material of 69 species. Included are holotypes of 31 species (together with 5 ones from Cretaceous amber), syntypes of 26 species (four of them are presently considered to be junior synonyms) and paratypes of 32 species (one of which is considered a junior synonym). Essential label data, references to original descriptions, and modern status including synonyms are given. PMID- 27394351 TI - Zygophylax kakaiba, a new species of hydroid (Cnidaria: Hydrozoa:
Zygophylacidae) from the Philippine Islands. AB - The genus Zygophylax Quelch, 1885 includes ca. 50 valid species of leptothecate hydroids that occur mainly in deep waters. Herein we describe Zygophylax kakaiba, sp. nov., collected in the Philippines at a depth of 580 m during the Siboga Expedition. Compared to its congeners, this species is distinguished by the abrupt curvature of the distal third of its hydrothecae towards the adcauline side. PMID- 27394352 TI - Description of a nomen nudum species of Liriomyza Mik and the first record of Liriomyza blechi Spencer from Brazil (Insecta: Diptera: Agromyzidae). AB - The nomen nudum Liriomyza flagellae is formerly described in this paper as Liriomyza valladaresae sp. nov., based on male and female specimens collected in the Brazilian Amazon and reared from leaves of Alternanthera tenella and Amaranthus viridis (Amaranthaceae). Information on the puparium and the biology of this new species are provided. The species Liriomyza blechi, previously recorded from the U.S.A., Guadeloupe and Dominican Republic, is newly recorded from Brazil, reared from leaves of Blechum pyramidatum (Acanthaceae) and Spigelia anthelmia (Loganiaceae). PMID- 27394353 TI - Eight new species of Cycloneuroterus Melika & Tang gallwasps from Taiwan and mainland China (Hymenoptera: Cynipidae: Cynipini). AB - Eight new species of cynipid gallwasps, Cycloneuroterus abei Melika & Tang, C. ergei Tang & Melika, C. gilvus Melika & Tang, C. globosus Melika & Tang, C. jianwui Tang & Melika, C. lohsei Melika & Tang, C. tumiclavus Tang & Melika, C. uraianus Tang & Melika, from Taiwan and mainland China are described. Descriptions, diagnoses, biology, and host associations for the new species and a key to all Cycloneuroterus species are given. All taxa are supported by morphological and molecular data. Seven newly described species induce galls on Quercus subgenus Cyclobalanopsis, while one, C. uraianus, induces galls on Castanopsis. This is the first Cycloneuroterus species known to associate with Castanopsis. PMID- 27394354 TI - Carcinoecium-forming Epizoanthus [Hexacorallia: Zoantharia] and the biology of E. papillosus in the eastern Atlantic, with special reference to the cnidom. AB - Epizoanthus is a poorly known zoantharian genus in need of further study. Benthic surveys have shown that E. papillosus (until recently considered rare) is quite abundant in the Celtic Sea, Minches and northern North Sea, occurring as carcin oecia formed in association with Anapagurus laevis (Anomura, Paguridae) and as smaller free-living colonies. It is also extensively distributed in the western Atlantic. A study of the cnidom in tentacles and mesenteric filaments has shown that carcinoecia contained fewer types and smaller numbers of nematocysts (basitrichs, p-mastigophores, and two different holotrich types) and spirocysts than free-living colonies, probably a consequence of being able to scavenge food from the pagurid. A method for obtaining quantitative estimates of spirocyst abundance is described. The mesenteric filaments of two of the three carcinoecia analysed contained numerous unexploded nematocysts (kleptocnidae) sequestered from the scyphomedusan Cyanea (probably C. capillata), presumably derived from the long tentacles trailing over the sea bed. This occurrence has never previously been recorded. The taxonomic study of larger, deep-sea, carcinoecium forming species of Epizoanthus is complicated by the same paucity of nematocysts noted for E. papillosus. PMID- 27394355 TI - Using Gordiid cysts to discover the hidden diversity, potential distribution,
and new species of Gordiids (Phylum Nematomorpha). AB - In this study, we sampled aquatic snails for the presence of hairworm cysts from 46 streams in Payne County, Oklahoma. Gordiid cysts were found at 70 % (32/46) of sites examined. Based on cyst morphology, we were able to identify three morphological types of gordiid cysts, including Paragordius, Gordius, and Chordodes/Neochordodes. Using our gordiid cyst presence data in conjunction with environmental variables, we developed an ecological niche model using Maxent to identify areas suitable for snail infections with gordiids. The model successfully predicted all presence localities of gordiid cysts in snails over a geographic area of 1,810 km2. We used this information, along with arthropod host infections and crowdsourcing, citizen scientists sampling for adult free-living worms during peak emergent times in areas predicted suitable by the model, to document Paragordius varius, Chordodes morgani, and a new species of gordiid (Gordius n. sp.). To our knowledge, this is the first ecological niche model attempted on such a narrow geographic scale (county level) that recovered known locations successfully. We provide new scanning electron micrographs and molecular data for these species. Our field data and ecological niche model clearly indicate that gordiid cysts are easy to detect in the environment and together these sampling techniques can be useful in discovering new species of gordiids, even in relatively well sampled areas for these cryptic parasites. PMID- 27394356 TI - A new species of Amaralia Fowler (Siluriformes: Aspredinidae) from the Parana Paraguay River Basin. AB - A new species of the banjo catfish genus Amaralia is described from the Parana Paraguay River Basin in central-western Brazil, Paraguay and northern Argentina. Amaralia oviraptor is distinguished from its single and allopatric congener, Amaralia hypsiura, by the greater number of dorsal-fin rays (3 vs. 2); by the absence of lateral contact between middle and posterior nuchal plates (vs. middle and posterior nuchal plates contacting each other laterally); and by a longer cleithral process (17.4-19.5 % of SL, mean 18.2 % vs. 14.0-17.2 % of SL, mean=15.5 %). Comments on the peculiar oophagic diet of Amaralia and an extended diagnosis of the genus are provided. PMID- 27394357 TI - New species of Rhagoletotrypeta (Diptera: Tephritidae) from the Dominican Republic and southern Brazil and Paraguay. AB - Rhagoletotrypeta chapecensis Norrbom & Savaris, new species, and R. gelabertae Norrbom & Savaris, new species, are described and illustrated from specimens from southern Brazil (Parana, Santa Catarina) and Paraguay, and from the Dominican Republic, respectively. The larvae of R. chapecensis develop in fruits of Celtis iguanaea (Jacq.) Sarg. (Ulmaceae). A key to the species of the xanthogastra species group is provided. PMID- 27394358 TI - Review of the Neotropical genus Helenus White, 1879, with description of a new species (Hemiptera: Heteroptera: Aradidae). AB - Since the description of Helenus hirsutus by Champion (1898) from Panama, it was unclear if this species was a synonym of Helenus hesiformis White, 1879 that was described from Brazil. Now it was possible to locate and compare type specimens of both species, that resulted in recognising them as valid species. In this contribution, a third species, Helenus wachteli n. sp. is described from Peru, and a key to all species of the genus Helenus is presented. PMID- 27394359 TI - A new species and new records of Pseudocephennium Reitter in Venezuela, with notes on movable endophallic structures (Coleoptera: Staphylinidae: Scydmaeninae). AB - Pseudocephennium auriculatum sp. n. is described, based on a male specimen collected in north-western Venezuela. New findings of Pseudocephennium maximum Jaloszynski and P. araguanum Jaloszynski, so far known only from holotypes, are reported. The aedeagi of newly found specimens have the endophallic structures extruded to various extent which makes it possible to identify movable components of the internal aedeagal armature. PMID- 27394361 TI - Review of the Polistes (Polistella) "Stenopolistes" species-group (Hymenoptera: Vespidae: Polistinae) from Vietnam, with description of a new species and key to species. AB - The "Stenopolistes" species-group of the subgenus Polistella Ashmead, 1904 comprising in Vietnam by six species. Polistes adsimilis Nguyen & Carpenter sp. nov. is described and figured. Polistes khasianus Cameron, 1900 is confirmed to occur in Vietnam, P. pallidus Gusenleitner, 2011 is newly recorded from Vietnam. A key to Vietnamese species is provided. The nest of P. khasianus is described. PMID- 27394360 TI - New Pergalumna (Acari, Oribatida, Galumnidae) from Peru. AB - Six species of oribatid mites of the genus Pergalumna (Oribatida, Galumnidae) are collected from the German Expedition to Amazonian Peru in 2013; of these, three are new for science, described from upper soil and leaf litter in the primary evergreen lowland rainforest. Pergalumna (Pergalumna) parapassimpunctata sp. nov. is morphologically most similar to P. (P.) passimpunctata Balogh & Mahunka, 1969, but differs from the latter by the presence of foveolate body surface, two pairs of porose areas Aa and minute interlamellar setae, and the absence of porose areas A3. Pergalumna (Pergalumna) krisperi sp. nov. is morphologically most similar to P. (P.) cardosensis Perez-Inigo & Baggio, 1986, but differs from the latter by the smaller body size, rostral and lamellar setae of medium size and the presence of four pairs of notogastral porose areas. Pergalumna (Pergalumna) lenticulata sp. nov. is morphologically most similar to P. (P.) decorata Balogh & Mahunka, 1977, but differs from the latter by the larger body size and the presence of lenticulus and bidentate rostrum. The species Pergalumna (Pergalumna) bryani Jacot, 1934 is recorded for the first time in Peru. PMID- 27394362 TI - New species of Claustropyga Hippa, Vilkamaa & Mohrig (Diptera, Sciaridae) from the Holarctic region. AB - The following four new species are described: Claustropyga clavulata sp. n. (Canada), C. lobigera sp. n. (Finland), C. modica sp. n. (Finland) and C. stupenda sp. n. (Canada, Russia). A fifth, probably new species is briefly discussed. Claustropyga stupenda has spectacular morphological characters in its hypopygium. There are now 23 species in Claustropyga. PMID- 27394363 TI - Taxonomic review of tropical western Atlantic shallow water Drilliidae (Mollusca: Gastropoda: Conoidea) including descriptions of 100 new species. AB - A review of the literature and examination of over 3,200 specimens of shallow water (<200 m) tropical western Atlantic (TWA) Drilliidae Olson, 1964 in museum and private collections has resulted in the recognition of numerous previously undescribed species, 100 of which are proposed here for the first time. A total of 65 names were found in the literature. Of these, 48 are considered valid, 16 synonyms, and one nomen dubium. In addition, characteristics that distinguish each genus currently in use for TWA shallow water species have indicated the need for reassignment (new combinations within Drilliidae) of 15 species. Some nomenclatural actions have come about from the literature review and include one taxon placed in junior synonymy (under an older name recently re-discovered) and one new name for a junior homonym. Two neotypes, five lectotype designations, and one new name are also proposed. Altogether, nomenclatural actions on 17% of valid previously described taxa are proposed. The 100 proposed names are placed in 12 available and one new genus: Agladrillia Woodring, 1928 (2), Bellaspira Conrad, 1868 (7), Calliclava McLean, 1971 (3), Cerodrillia Bartsch & Rehder, 1939 (11), Clathrodrillia Dall, 1918 (6), Decoradrillia, new genus (4), Douglassia Bartsch, 1934 (4), Fenimorea Bartsch, 1934 (15), Leptadrillia Woodring, 1928 (12), Lissodrillia Bartsch & Rehder, 1939 (8), Neodrillia Bartsch, 1943 (2), Splendrillia Hedley, 1922 (13), and Syntomodrillia Woodring, 1928 (13). These are the first reports of Calliclava in the western Atlantic, previously known only from the eastern Pacific. The new genus, Decoradrillia, is proposed to hold four new species and one existing that share a unique shell microsculpture and other morphological traits. One genus, Drillia Gray, 1838, is not currently believed to have TWA representatives. Three genera comprised exclusively of bathyal species are not treated in this work: Clavus Monfort, 1810 (=Eldridgea Bartsch, 1934), Globidrillia Woodring, 1928, and Spirotropis Sars, 1878. The significant increase in species within all of the genera has the effect of strengthening the groups' diagnostic characters by their presence across a greater number of species. Each of the 148 valid species treated herein are described (or redescribed) and photographs of types presented, as are photographs of morphological variants and representatives from separate geographic areas, if available, to illustrate species' variability. PMID- 27394364 TI - New Prionospio and Aurospio Species from the Deep Sea (Annelida: Polychaeta). AB - The number of records of the genus Prionospio Malmgren, 1867, from the deep sea (>2000 m) are relatively few and do not reflect the actual occurrence of species nor their potential ecological importance. In this paper we describe five new species of this genus (Prionospio amarsupiata sp. nov., P. vallensis sp. nov., P. branchilucida sp. nov., P. hermesia sp. nov. and P. kaplani sp. nov.) all of which are abundant members of the deep-sea community. We also describe two new species of the genus Aurospio Maciolek, 1981 (Aurospio abranchiata sp. nov. and A. tribranchiata sp. nov.) again common elements of the abyssal fauna. Two of the new species have characters which question the generic distinctiveness of Prionospio and Aurospio. The problems in differentiating these two genera are discussed. PMID- 27394365 TI - Alfredo Duges' type specimens of amphibians and reptiles revisited. AB - The type specimens of amphibians and reptiles of the Museo de Historia Natural Alfredo Duges, at the University of Guanajuato (MADUG) were reviewed following Smith & Necker's (1943) summary. Owing to this collection's eventful history and its historical importance as the oldest herpetological collection in Mexico, a review of its conservation status was needed. After many years, the collection has received proper recognition at the University of Guanajuato with a portion of the herpetological types considered "Precious Assets" of the university. We found 34 type specimens pertaining to 18 taxa; six are additional specimens to those previously reported; six herpetological types are missing, including the body of the type of Adelophis copei. All specimens are in good to reasonable condition except for the type of Rhinocheilus antonii, which has dried out completely. All specimens are illustrated to show their condition. PMID- 27394366 TI - Rhizoecus colombiensis Ramos & Caballero, a new species of hypogeal mealybug (Hemiptera: Coccomor. AB - A new species belonging to Rhizoecus Kunckel d'Herculais (Hemiptera: Coccomorpha: Rhizoecidae) is described, with hosts and distribution data in the New World. A dichotomous and illustrated key for the twelve species of Rhizoecus recorded from Colombia is presented. PMID- 27394367 TI - Lissodendoryx (Ectyodoryx) Lundbeck, 1909 (Coelosphaeridae, Poecilosclerida, Demospongiae) from Southern Chile: new species and a discussion of morphologic characters in the subgenus. AB - Our ongoing studies of the Chilean sponge fauna revealed four new species of Lissodendoryx (Ectyodoryx) that are described here, including three from the fjord's region (< 30 m depth, L.(E.) ballena sp. nov., L. (E.) corrugata sp. nov., L. (E.) coloanensis sp. nov.), and one from the deep waters off Diego Ramirez Archipelago (ca. 2000 m, L. (E.) diegoramirezensis sp. nov.). In addition, the type of L. (E.) anacantha was revised and found to bear much larger acanthostyles than originally reported. Our results revealed skeletal architectures quite distinct from that reported from the type species of L. (Ectyodoryx), and not predicted in the current diagnosis of Lissodendoryx, requiring an amended diagnosis. Ectosomal megascleres also set the majority of the new species apart from the type species of L. (Ectyodoryx), which does not have terminally microspined (sub)tylotes. This character is widespread in Lissodendoryx and might be pointing to phylogenetic affinities across the current subgeneric arrangement. Further morphologic characters and alternative phylogenetic scenarios are discussed, including hymedesmiid and myxillid affinities of the species described here. PMID- 27394368 TI - The family Cavognathidae (Coleoptera: Cucujoidea) in Argentina and adjacent countries. AB - The family Cavognathidae (Coleoptera: Cucujoidea) in Argentina is represented by three species of the genus Taphropiestes Reitter, 1875: T. fusca Reitter, 1875 [Chubut], T. magna Slipinski & Tomaszewska, 2010 [Rio Negro; Chubut], and T. plaumanni Slipinski & Tomaszewska 2010 [Buenos Aires]. A total of 2565 larvae (multiple instars), 83 pupae, 2028 live adults, and 16 dead adults of T. plaumanni were found in Argentina between 2005 and 2013 in the nests of birds representing the families Columbidae, Emberizidae, Falconidae, Furnariidae, Hirundinidae, Mimidae, Passeridae, Psittacidae, Troglodytidae and Tyrannidae. The adults were most abundant in closed mud nests of Furnarius rufus (Gmelin, 1788) [Furnariidae] and its inquiline birds, but the larvae were most abundant in wood nest boxes. When T. plaumanni was scarcely represented in bird nests from some localities, Alphitobius diaperinus (Panzer, 1797), an exotic darkling beetle [Col.: Tenebrionidae: Tenebrioninae], and one native species, Phobelius crenatus Blanchard, 1842 [Col.: Tenebrionidae: Lagriinae], were most abundant in stick nests of Furnariidae. In contrast, when A. diaperinus and P. crenatus were absent in one locality from the province of Buenos Aires, T. plaumanni was the most abundant beetle. A complete account of data is provided for these collections of T. plaumanni in Argentina. Known distributional data for all Argentinian species of Taphropiestes are plotted on maps with biogeographical provinces indicated. PMID- 27394369 TI - Two new species of freshwater flatworms (Platyhelminthes: Tricladida: Continenticola) from South American caves. AB - The diversity of freshwater triclads in the Neotropical region is considered to be low, but extensive areas of South America remain almost unexplored. Herein we describe two cave-dwelling, new species of Girardia, one from a transition zone of the Cerrado and Caatinga phytophysiognomies and the other from the Cerrado phytophysiognomy. The species from the Cerrado-Caatinga transition is a troglobite, eyeless and whitish; the species from the Cerrado area is possibly a troglophile, since it shows heavily pigmented body and eyes. Each species is easily recognized by a unique combination of features in its external morphology and copulatory apparatus. The two new species of Girardia show a restricted distribution, even the troglophile, and occur in caves without legal protection. Therefore, they must be considered as vulnerable organisms in a conservation context. PMID- 27394370 TI - A new species in the indigenous New Zealand soft scale insect genus Kalasiris Henderson & Hodgson (Hemiptera: Sternorrhyncha: Coccomorpha: Coccidae) on Gahnia setifolia (Cyperaceae). AB - The genus Kalasiris Henderson & Hodgson (Hemiptera: Sternorrhyncha: Coccomorpha: Coccidae) is currently only known from New Zealand. The adult female and pupa of a new species, K. martini Hodgson & Richmond are described and illustrated below and the possible taxonomic relationships of the genus to other New Zealand genera are discussed. PMID- 27394371 TI - Endogean and cavernicolous Coleoptera of the Balkans. XV. A new species of the genus Ioniorhynchus Magrini, Meoli & Abbazzi, 2005 (Coleoptera: Curculionidae: Entiminae) from Greece. AB - Ioniorhynchus henderickxi sp. nov. is described and illustrated from Zakynthos, Spilia Cagioti-Giri, Greece. The new species is compared closely with the sympatric I. doriae A. & F. Solari 1904. The taxonomic status of the genus is discussed, and an annotated catalogue of all anopthalmous species of the tribe Otiorhynchini of Balkan Peninsula is provided. PMID- 27394372 TI - Suggestion of Raspailia (Hymeraphiopsis) septentrionalis as replacement name for Raspailia (Hymeraphiopsis) fruticosa Lehnert & Stone, 2015. AB - Shortly after publication of Raspailia (Hymeraphiopsis) fruticosa Lehnert & Stone, 2015 Rob Van Soest (pers. communication) noticed that this species name is a junior primary homonym of Raspailia fruticosa Dendy, 1887, now accepted as Endectyon fruticosa. According to the ICZN the published species name is unavailable and we now suggest to replace the name with Raspailia (Hymeraphiopsis) septentrionalis (holotype deposited at the Zoologische Staatssammlung Munchen, ZSM 20150392, collection data published in Lehnert & Stone 2015). PMID- 27394373 TI - Contribution to the knowledge of Lanta Hebard, 1921, with remarks on some male genital characters (Blattaria, Ectobiidae). AB - The genus Lanta Hebard 1921 includes three species found in the Neotropical region. Two species are known from Argentina, L. peniculiger (province of Santa Fe), and L. scotia (provinces of Cordoba and Santiago del Estero) (see Crespo et al. 2010), and one from Brazil, L. borgesae, (Araras, Sao Paulo) (Rocha e Silva & Vasconcellos, 1984). All species have been described on the basis of male external characters, such as wing veins, leg spines, hypandrium, shape and position of the styli, in addition to coloration and size. Except for a partial representation of the male genitalia of L. borgesae (Rocha e Silva & Vasconcellos 1984), this structure went untreated in morphological and phylogenetic investigations of the Blattaria (Snodgrass 1937; McKittrick 1964; Grandcolas 1996; Klass 1997; Roth 2003;). Females remain unknown. PMID- 27394374 TI - Two new species of the genus Kabakra Dworakowska from Thailand (Hemiptera: Cicadellidae: Typhlocybinae). AB - The leafhopper genus Kabakra was established with Kabakra augusta from Vietnam as its type species by Dworakowska (1979). Later, another two species were described from India (Sohi & Mann 1992, Mathew & Ramakrishnan 1996). The genus was reviewed by Cao et al. (2012), who redescribed the genus and added three new species from China and Thailand. So far, six species have been reported, all from the Oriental region (see Dmitriev, 2016). In the present paper, two new species, K. chaiyaphuma and K. sakona spp. nov. are described and illustrated, with a key and a checklist to all known species of Kabakra. PMID- 27394375 TI - Ictal unilateral blinking is an unreliable lateralizing sign in tuberous sclerosis complex. AB - OBJECTIVE: Ictal unilateral blinking is an uncommon but reportedly reliable lateralizing sign, indicating an ipsilateral seizure focus. We aimed to determine its lateralizing utility in patients with tuberous sclerosis complex (TSC). METHODS: We reviewed the video-EEGs of 92 children with TSC and drug-resistant epilepsy. Eleven (12%) had seizures with unilateral blinking, of which 10 underwent epilepsy surgery. Lateralization of seizures was inferred from other semiology, ictal scalp EEG and outcome following tuberectomy. RESULTS: Seizures manifesting with unilateral blinking were focal motor in four patients, focal motor evolving into epileptic spasms in six, and epileptic spasms with focal features in one. Associated unilateral facial contraction was seen in five patients and arm jerking in four. Lateralized scalp ictal rhythms were seen in seven patients. Following tuberectomies, seven patients are seizure free and two had >90% reduction. Overall lateralization of seizures with unilateral blinking was contralateral in six patients and ipsilateral in four. When unilateral blinking was early in seizures, overall lateralization was more often contralateral (6/7 patients, PPV 85%). SIGNIFICANCE: Ictal unilateral blinking is not infrequent but unreliable in lateralizing seizures in TSC. Unrecognized seizure propagation to contralateral symptomatogenic regions and potentially different mechanisms may account for the variable lateralization. PMID- 27394376 TI - Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy. AB - OBJECTIVE: Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). METHODS: Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). RESULTS: In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. SIGNIFICANCE: Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the contralateral hippocampus after surgery suggests the possibility of an early post operative imaging marker to predict surgical outcome. PMID- 27394377 TI - Outcomes of endoscopic third ventriculostomy in adults. AB - Endoscopic third ventriculostomy (ETV) is an alternative to ventriculoperitoneal shunting for treatment of hydrocephalus. Studies have reported favorable outcomes for up to three-quarters of adult patients. We performed the first ETV outcomes study using an administrative claims database, examining current practice for adult patients in the United States. We interrogated the Truven Health MarketScan(r) database for Current Procedural Terminology codes corresponding to ETV and ventriculoperitoneal shunt from 2003- to 2011, including patients over 18years and data from initial and subsequent hospitalizations. ETV failure was defined as any subsequent ETV or shunt procedure. Five hundred twenty-five patients underwent ETV with 6months minimum follow-up. Mean age was 45.9years (range: 18-86years). Mean follow-up was 2.2years (SD: 1.6years, range: 0.5 8.4years). Etiology of hydrocephalus was 21.3% tumor, 9.0% congenital/aqueductal stenosis, 15.8% hemorrhage, and 53.9% others. ETV was successful in 74.7% of patients. Of 133 who failed, 25 had repeat ETV; 108 had shunt placement. Longer length of stay for index surgery was associated with higher risk of failure (hazard ratio (HR): 1.03, p<0.001), as was history of previous shunt (HR: 2.45, p<0.001). Among patients with repeat surgeries, median time to failure was 25days. This study represents a longitudinal analysis of nationwide ETV practice over 9years. Success rate in this large cohort is similar to that published by other single-center retrospective studies. Age and geographic variation may be associated with surgeon choice of ETV or shunt placement after failure of the initial ETV. PMID- 27394378 TI - Transcranial magnetic stimulation (TMS) in stroke: Ready for clinical practice? AB - The use of transcranial magnetic stimulation (TMS) in stroke research has increased dramatically over the last decade with two emerging and potentially useful functions identified. Firstly, the use of single pulse TMS as a tool for predicting recovery of motor function after stroke, and secondly, the use of repetitive TMS (rTMS) as a treatment adjunct aimed at modifying the excitability of the motor cortex in preparation for rehabilitation. This review discusses recent advances in the use of TMS in both prediction and treatment after stroke. Prediction of recovery after stroke is a complex process and the use of TMS alone is not sufficient to provide accurate prediction for an individual after stroke. However, when applied in conjunction with other tools such as clinical assessment and MRI, accuracy of prediction using TMS is increased. rTMS temporarily modulates cortical excitability after stroke. Very few rTMS studies are completed in the acute or sub-acute stages after stroke and the translation of altered cortical excitability into gains in motor function are modest, with little evidence of long term effects. Although gains have been made in both of these areas, further investigation is needed before these techniques can be applied in routine clinical care. PMID- 27394379 TI - Symptom resolution in infiltrating WHO grade II-IV glioma patients undergoing surgical resection. AB - Past studies of morbidity in patients with infiltrating gliomas have focused on the impact of surgery on quality of life. Surprisingly, little attention has been given to the rate at which the presenting symptoms improve after surgery, even though this is often the patient's first concern. This study is an initial effort to provide useful information about symptom resolution and factors predicting persistence of symptoms in glioma patients who undergo surgery. We conducted a retrospective analysis on patients who underwent surgery for World Health Organization (WHO) grade II-IV astrocytoma/oligodendroglioma/oligoastrocytoma at our institution. All patients were seen 2-4months postoperatively, and asked about the persistence of symptoms they experienced preoperatively. Symptoms reported in clinic were assessed against symptoms reported prior to surgery. Our study includes 56 consecutive patients undergoing surgery for gliomas. Of patients who experienced symptoms initially, headache resolved in 18/27 postoperatively, weakness resolved in 8/14 postoperatively, altered mental status resolved in 8/12 postoperatively, vision problems resolved in 7/11 postoperatively, nausea resolved in 5/7 postoperatively, and ataxia resolved in 4/5 postoperatively. Headache was more likely to resolve in patients with frontal or temporal tumors (p=0.02). Preoperative Karnofsky Performance Scale (KPS) of 70 or less was associated with longer postsurgical hospital stay (p<0.01). Younger patients were more likely to experience a resolution of altered mental status (p=0.04). Our analysis provides data regarding the rate at which surgery alleviates patient symptoms and considers variables predicting likelihood of symptom resolution. Some patients will experience symptom resolution following resection of WHO grade II-IV gliomas in the months following surgery. PMID- 27394380 TI - The LITE study: Rationale and protocol for a randomized controlled trial of light therapy for cancer-related fatigue in cancer survivors. AB - Fatigue is a common and distressing symptom that can last for months or years in up to one-third of cancer survivors. Despite its prevalence, the nature and mechanisms of cancer-related fatigue are poorly understood and the available treatments may not provide sufficient relief. Fatigue has been identified as a significant contributor to decreased quality of life, making it an important target for intervention. One approach that may be a safe and inexpensive treatment is bright light therapy. METHODS: This study is a 4-week blinded randomized controlled trial. Subjects will be men and women who meet criteria for cancer-related fatigue and have completed cancer treatment. Subjects will be randomly assigned to receive a Litebook treatment device that produces either bright white light (treatment) or dim red light (active control). The devices will be used daily for 30min upon waking for a period of four weeks. The primary outcome, fatigue, will be measured with the Multidimensional Fatigue Symptom Inventory-SF. Secondary outcomes include mood disturbance, sleep quality, quality of life, diurnal cortisol, and inflammatory biomarkers. Fatigue assessments will be completed weekly and secondary outcomes will be assessed at pre- and post intervention. CONCLUSIONS: The current research will examine the effect of light exposure on cancer-related fatigue and its potential psychological, behavioral, and biological mechanisms. If successful, this research would support the use of light therapy for the management of persistent fatigue in cancer survivors, expanding existing treatment options. It may also improve upon the current understanding of the mechanisms that underlie cancer-related fatigue. PMID- 27394381 TI - An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and growth restriction (TEST): Trial protocol. AB - OBJECTIVE: Pre-eclampsia remains a worldwide cause of maternal and perinatal morbidity and mortality. Low dose aspirin (LDA) can reduce the occurrence of pre eclampsia in women with identifiable risk factors. Emerging screening tests can determine the maternal risk of developing placental disease, such as pre eclampsia from the first trimester of pregnancy. The aim of this study is to determine if it is more beneficial in terms of efficacy and acceptability to routinely prescribe LDA to nulliparous low-risk women compared to test indicated LDA on the basis of a positive screening test for placental disease. METHODS: We propose a three armed multi-center open-labeled randomized control trial of; (i) routine LDA, (ii) no aspirin, and (iii) LDA on the basis of a positive first trimester pre-eclampsia screening test. LDA (75mg once daily) shall be given from the first trimester until 36-week gestation. The primary outcome measures include; (i) the proportion of eligible women that agree to participate (acceptability), (ii) compliance with study protocol (acceptability and feasibility), (iii) the proportion of women in whom it is possible to obtain first trimester trans-abdominal uterine artery Doppler examination (feasibility) and (iv) the proportion of women with a completed screening test that are issued the screening result within one week of having the test performed (feasibility). CONCLUSION: This will be the first clinical trial to determine the efficacy and acceptability in low-risk women of taking routine LDA versus no aspirin versus LDA based on a positive first trimester screening test for the prevention of placental disease. PMID- 27394382 TI - A randomized trial of diet and physical activity in women treated for stage II-IV ovarian cancer: Rationale and design of the Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES): An NRG Oncology/Gynecologic Oncology Group (GOG 225) Study. AB - Ovarian cancer is the most common cause of gynecological cancer death in United States women. Efforts to improve progression free survival (PFS) and quality of life (QoL) after treatment for ovarian cancer are necessary. Observational studies suggest that lifestyle behaviors, including diet and physical activity, are associated with lower mortality in this population. The Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) NRG 0225 study is a randomized, controlled trial designed to test the hypothesis that a 24month lifestyle intervention will significantly increase PFS after oncological therapy for stage II-IV ovarian cancer. Women are randomized 1:1 to a high vegetable and fiber, low-fat diet with daily physical activity goals or an attention control group. Secondary outcomes to be evaluated include QoL and gastrointestinal health. Moreover an a priori lifestyle adherence score will be used to evaluate relationships between adoption of the diet and activity goals and PFS. Blood specimens are collected at baseline, 6, 12 and 24months for analysis of dietary adherence (carotenoids) in addition to mechanistic biomarkers (lipids, insulin, telomere length). Women are enrolled at NRG clinic sites nationally and the telephone based lifestyle intervention is delivered from The University of Arizona call center by trained health coaches. A study specific multi-modal telephone, email, and SMS behavior change software platform is utilized for information delivery, coaching and data capture. When completed, LIVES will be the largest behavior-based lifestyle intervention trial conducted among ovarian cancer survivors. PMID- 27394383 TI - Translation of the Care of Persons with Dementia in their Environments (COPE) intervention in a publicly-funded home care context: Rationale and research design. AB - BACKGROUND: Dementia is the leading cause of loss of independence in older adults worldwide. In the U.S., approximately 15 million family members provide care to relatives with dementia. This paper presents the rationale and design for a translational study in which an evidence-based, non-pharmacologic intervention for older adults with dementia and family caregivers (CGs) is incorporated into a publicly-funded home care program for older adults at risk for nursing home admission. METHODS: The 4-month Care of Persons with Dementia in their Environments (COPE) intervention is designed to optimize older adults' functional independence, and to improve CG dementia management skills and health-related outcomes. COPE features 10 in-home occupational therapy visits, and 1 in-home visit and 1 telephone contact by an advanced practice nurse. COPE was deemed efficacious in a published randomized clinical trial. In the present study, older adults with dementia enrolled in the Connecticut Home Care Program for Elders (CHCPE) and their CGs are randomly assigned to receive COPE plus their ongoing CHCPE services, or to continue receiving CHCPE services only. OUTCOMES: The primary outcome for older adults with dementia is functional independence; secondary outcomes are activity engagement, quality of life, and prevention or alleviation of neuropsychiatric symptoms. CG outcomes include perceived well being and confidence in using activities to manage dementia symptoms. Translational outcomes include net financial benefit of COPE, and feasibility and acceptability of COPE implementation into the CHCPE. COPE has the potential to improve health-related outcomes while saving Medicaid waiver and state revenue funded home care program costs nationwide. PMID- 27394384 TI - Results of a near continuous glucose monitoring technology in surgical intensive care and trauma. AB - INTRODUCTION: Near-continuous glucose monitoring is expected to increase time in range (TIR) of 80-120mg/dL and to avoid hypoglycemia without increasing workload. We investigated a near-continuous glucose monitor in surgical critically ill and trauma patients. METHODS: Patients were enrolled at a surgical intensive care unit associated with a level 1 trauma center. Glucose measurements were compared to the gold standard Yellow Springs Instrument (YSI). The technology withdraws 0.13mL of blood every 15min from a central venous line, centrifuges the sample, and uses mid-infrared spectroscopy to measure glucose. We plotted a Clarke Error Grid, calculated Mean Absolute Relative Deviation (MARD) to analyze trend accuracy, and we present a Bland Altman plot of device versus standard glucose measurements. RESULTS: 24 patients were enrolled. One patient was withdrawn due to poor blood return from central venous line. A total of 347 glucose measurements from 23 patients were compared to the gold standard. 94.8% of the data points were in zone A of the Clarke Error Grid and 5.2% in zone B. The MARD was 8.02%. The majority of data points achieved the benchmark for accuracy. The remaining 5.2% are clinically benign. The MARD was below 10%. The Bland Altman plot shows good agreement between the device and reference glucose measurements. There were no device related adverse events. CONCLUSION: Our data suggests that near continuous monitoring via infrared spectroscopy is safe and accurate for use in critically ill surgical and trauma patients. A large scale multi-center study is underway to confirm these findings. PMID- 27394385 TI - Rationale and study protocol for a multi-component Health Information Technology (HIT) screening tool for depression and post-traumatic stress disorder in the primary care setting. AB - The prevalence rate of depression in primary care is high. Primary care providers serve as the initial point of contact for the majority of patients with depression, yet, approximately 50% of cases remain unrecognized. The under diagnosis of depression may be further exacerbated in limited English-language proficient (LEP) populations. Language barriers may result in less discussion of patients' mental health needs and fewer referrals to mental health services, particularly given competing priorities of other medical conditions and providers' time pressures. Recent advances in Health Information Technology (HIT) may facilitate novel ways to screen for depression and other mental health disorders in LEP populations. The purpose of this paper is to describe the rationale and protocol of a clustered randomized controlled trial that will test the effectiveness of an HIT intervention that provides a multi-component approach to delivering culturally competent, mental health care in the primary care setting. The HIT intervention has four components: 1) web-based provider training, 2) multimedia electronic screening of depression and PTSD in the patients' primary language, 3) Computer generated risk assessment scores delivered directly to the provider, and 4) clinical decision support. The outcomes of the study include assessing the potential of the HIT intervention to improve screening rates, clinical detection, provider initiation of treatment, and patient outcomes for depression and post-traumatic stress disorder (PTSD) among LEP Cambodian refugees who experienced war atrocities and trauma during the Khmer Rouge. This technology has the potential to be adapted to any LEP population in order to facilitate mental health screening and treatment in the primary care setting. PMID- 27394386 TI - Prepare, a randomized trial to promote and evaluate weight loss among overweight and obese women planning pregnancy: Study design and rationale. AB - BACKGROUND: Women who are overweight or have obesity at pregnancy onset, and those who gain excessive weight during pregnancy, are at increased risk of pregnancy-related complications and large for gestational age infants. OBJECTIVE: This report describes methodology for the Prepare study, a randomized, controlled clinical trial testing a preconception and pregnancy weight management program for women who are overweight or have obesity (BMI>=27kg/m(2)). OUTCOMES: This trial examines multiple pregnancy and neonatal outcomes, with the primary outcome being gestational weight gain (GWG). Secondary outcomes include change in weight before conception, offspring birth weight adjusted for gestational age, offspring weight for length, and pregnancy diet quality and physical activity level. METHODS: Nonpregnant women who anticipate becoming pregnant in the next 2years are randomly assigned to an intervention program or a usual care control condition. Intervention participants receive weight management counseling by telephone before and during pregnancy, with weekly contacts during the first 6months and monthly contacts for the next 18months. Intervention participants also have unlimited access to a study website that provides self-management tools. All participants who become pregnant are contacted at 20weeks' gestation to assess physical activity levels and dietary habits. All other outcome data are obtained from medical records. Intervention satisfaction is assessed via questionnaire. SUMMARY: This clinical trial tests the efficacy of an intervention program designed to help overweight and obese women achieve healthy lifestyle changes that will result in a healthy weight prior to pregnancy and appropriate weight gain during pregnancy. PMID- 27394388 TI - Botanical drugs in Ayurveda and Traditional Chinese Medicine. AB - ETHNOPHARMACOLOGICAL RELEVANCE: China and India have a long history in the therapeutic application of botanical drugs in traditional medicine. Traditional Chinese Medicine (TCM) and Ayurveda are considered as two of the most ancient systems of medicine, with history of more than two millennia. Medicinal plants are the principal medicinal materials used in both these systems. AIM OF THE REVIEW: This review discusses about the histories of Ayurveda and TCM, the common medicinal plants species, the drug processing strategies used, and the current statuses of these traditional systems of medicine (TSM). Through the views presented in this article, we aim to provide a new perspective to herbal drug researchers for expanding and improving the utilization of botanical drugs and their therapeutic applications. METHODS: A bibliographic investigation of Chinese and Indian pharmacopoeias, monographs and official websites was performed. Furthermore, information was obtained from scientific databases on ethnobotany and ethno medicines. RESULTS: The review of Ayurveda and TCM ethno medicine indicates that both these systems have many medicinal materials in common. The studies carried out by the authors for comparison of plants from same genus from both these TSM's have been discussed to further bring focus to the utilization of "qualitatively" similar species which can be utilized and substituted for endangered or economically valued species. The overview of ancient literature and scientific findings for drugs in both these systems suggests that, the botanical drugs used in common and their processing methods can be explored further for extensive utilization in traditional medicine. CONCLUSION: This review describes the histories, common medicinal plant species, their processing methods and therapeutic applications in Ayurveda and TCM. The insights provided through this article may be used by herbal drug researchers and pharmacologists for further exploration of botanical drugs from these two traditional systems of medicine. PMID- 27394387 TI - Safety assessment of a traditionally used extract from leaves of Boldoa purpurascens. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Boldoa purpurascens Cav. (Nyctaginaceae) is a plant species used in traditional medicine in Cuba as a diuretic. AIM OF THE STUDY: The aim of the present investigation was to evaluate the safety profile of a hydroalcoholic extract from leaves of Boldoa purpurascens. MATERIALS AND METHODS: First, an experimental study to assess the oral acute toxicity at a dose of 2000mg/kg body weight of the extract was carried out. Potential genotoxicity of the extract was evaluated using the Ames test and the micronucleus induction assay in mouse bone marrow. In the Ames test a concentration range of 50, 100, 150, 300 and 500ug/plate was tested. In the micronucleus induction assay, doses of 500, 1000 and 2000mg/kg of body weight were tested. For completeness, since the extract contains saponins, the evaluation of the hemolytic activity, ocular and skin irritation were included. RESULTS: No signs or symptoms of toxicity were observed in the oral acute toxicity test (body weight at baseline, seven days and end of the experiment of 236.41+/-20.07, 256.81+/-30.44 and 240.02+/-26.16 respectively for the treated group). The hydroalcoholic extract from the leaves was not mutagenic in the Ames test, and no genotoxicity was observed in the micronucleus assay. A hemolysis test at concentration of 1mg/mL confirmed hemolytic activity, which is not a safety concern since saponins are not absorbed after oral administration. In order to evaluate the percentage of protein denaturation, the ocular irritability index was calculated. The extract was found to be irritating. Finally, skin irritability was evaluated and the irritation index was equal to zero. CONCLUSIONS: Based on the toxicological evaluation of a traditionally used hydroalcoholic extract from the leaves of Boldoa purpurascens we can confirm the safety of its oral use. PMID- 27394389 TI - Possible similarities between the folk medicine historically used by First Nations and American Indians in North America and the ethnoveterinary knowledge currently used in British Columbia, Canada. AB - AIMS OF THE STUDY: This paper compares sixty-four plants used as ethnoveterinary remedies in British Columbia with First Nations folk medicine. MATERIALS AND METHODS: In 2003, I conducted semi-structured interviews with 60 participants obtained using a purposive sample. The data was then compared with historical documents on First Nations plant use. RESULTS: Exact parallels between First Nations/native American folk medicine and ethnoveterinary remedies used for farm animals and horses were Acer macrophyllum Pursh, Epilobium angustifolium L. and Lonicera involucrata (Richardson) Banks ex Spreng., used as stimulants and tonics for goats; Achlys tripylla DC. as a fly repellent in barns, Alnus rubra Bong., for rabbits' dental care, Berberis repens Lindl., Rumex crispus L., to treat sores and rashes on horses, Pinus ponderosa Douglas ex C. Lawson for stomach problems and Bovista pila Berk. and M. A. Curtis and Dolichousnea longissima (Ach.) Articus used on wounds. CONCLUSION: This study revealed the parallel uses between sixty-four plants used as ethnoveterinary medicines in British Columbia and the folk medicines used by the First Nations peoples and by native American groups. PMID- 27394390 TI - The Post-genomic Era of Trichoderma reesei: What's Next? AB - The ascomycete Trichoderma reesei is one of the most well studied cellulolytic microorganisms. This fungus is widely used in the biotechnology industry, mainly in the production of biofuels. Due to its importance, its genome was sequenced in 2008, opening new avenues to study this microorganism. In this 'post-genomic' era, a transcriptomic and proteomic era has emerged. Here, we present an overview of new findings in the gene expression regulation network of T. reesei. We also discuss new rational strategies to obtain mutants that produce hydrolytic enzymes with a higher yield, using metabolic engineering. Finally, we present how synthetic biology strategies can be used to create engineered promoters to efficiently synthesize enzymes for biomass degradation to produce bioethanol. PMID- 27394391 TI - Axillary node metastatic carcinoma without definitive primary: a case report. AB - Cancer of unknown primary (CUP) is the finding of a metastatic cancerous lesion without an established primary source localized within the body. CUP can be of any cancer cell type, however, adenocarcinoma is most often identified by histology. Up to 5% of all malignant diagnoses are classified as CUP. PET is an imaging modality often utilized to distinguish a primary source in the setting of CUP, yet often a primary is never identified. CUP can be further stratified using specific qualifiers as favorable and unfavorable, indicating the potential therapeutic response to treatment regimens. Treatment approach to CUP relies heavily on the cell type identified by histology, the location of the lesion, and the amount of spread within the body. In the typical setting and presentation, per current literature, CUP arises in the 7th decade of life in patients with multiple comorbidities, and often has a poor prognostic value. This case report identifies an atypical presentation of CUP, a 38-year-old Caucasian female with an axillary mobile mass, and no associated systemic symptoms. Biopsy of the node and immunohistochemical staining showed histology consistent with metastatic carcinoma. Mammography, MRI, and PET scan found no evidence of tumor primary or distant metastasis. Further staining confirmed metastatic carcinoma consistent with breast origin, without an established breast primary. As in this case, CUP may present in an atypical manner, warranting a thorough investigation aiming to identify the tumor primary to aid in identification of a proper treatment regimen and approach. PMID- 27394392 TI - Spontaneous postoperative choledochoduodenal fistula due to bile duct injury following laparoscopic cholecystectomy. AB - INTRODUCTION: Bile leak after cholecystectomy which is the frequency less than 2% is an important problem for patients. Some bile duct injuries occuring after laparoscopic cholecystectomy are the complex bile duct injuries and can cause bile leak and fistula. PRESENTATION OF CASE: A 74-year-old woman has high output bile drainage from abdominal drain after laparoscopic cholecystectomy so an ERCP was performed. It was clear that there was a complete transaction of bile ducts, however this finding was inconsistent with the patient's clinical situation. The bile drainage of the patient was ceased and she was discharged to home without any problem. Four months later the patient was admitted again for recurrent cholangitis episodes. Patient was operated to perform a biliary-enteric diversion for the suspicion of biliary stricture. There was a thin fistula tract over the duodenum that was previously seperated from the proximal choledochus. The distal part of the bile duct was ended blindly. A hepaticojejunostomy anastomosis over a transhepatic stenting was performed. DISCUSSION: The circumferential injuries are the most common and devastating injuries leading to bile leak, peritonitis and varying degrees of sepsis. The probability of a bile fistula to close spontaneously is almost impossible in cases of iatrogenic circumferential full thickness injuries. CONCLUSION: In the present case we have reported a case of Bismuth type 2 (Strasberg type E2) injury in which the biliary drainage was closed spontaneously with the formation of spontaneous biliary-duodenal fistula. It is an extremely interesting case that has not been reported in the literature previously. PMID- 27394393 TI - Unusual non progressive idiopathic giant ascending aortic aneurysm-A rarity. AB - INTRODUCTION: Ascending aortic aneurysm is the second most common aortic aneurysm to abdominal aortic aneurysm. Most ascending aortic aneurysm is diagnosed in sixth or seventh decade of life. Majority of patients of ascending aortic aneurysm do not have any clinical manifestations. CASE PRESENTATION: 45year old female patient presented with Dyspnoea on exertion (NYHA class II-III), palpitation and vague chest pain since 2 years. Patient had worsening of symptoms NYHA IV dyspnoea since last 1 month and the patient managed with medications since the patient was not willing for surgery. Patient is on regular follow up on medications since last 2 years. DISCUSSION: Aneurysms are usually dilation of an arterial segment. It involves extensive area of the aorta and is a challenging surgical procedure especially when it involves aortic root. Computed Tomography (CT), and especially multi-detector CT (MDCT), is the most popular radiological modality for evaluating aortic aneurysms. CONCLUSION: Aortic aneurysms are localized dilation of the wall of aorta. They can rupture or dissect involving the pericardium, aortic valve. Open surgical repair remains the standard approach to treating most large aortic aneurysm and results are believed to be more predictable and satisfactory. PMID- 27394394 TI - Acute acalculous cholecystitis as a rare manifestation of chronic mesenteric ischemia. A case report. AB - INTRODUCTION: Symptomatic chronic mesenteric ischemia (CMI) is an uncommon condition that usually presents with intestinal angina, sitophobia and unintentional weight loss. Acute acalculous cholecystitis (AAC) has very rarely been described in the settings of CMI. PRESENTATION OF CASE: We describe a case of a 73year old man that developed an AAC as a complication of CMI. The patient underwent a simultaneous cholecystectomy and open aortic revascularization which was successful. At 24 months of follow-up the patient is clinically well and regained weight. DISCUSSION: Ischemia has been considered an important etiology for the development of AAC. In the settings of CMI, an AAC might develop has a herald sign of progression to acute mesenteric ischemia and infarction, as the cystic artery is a terminal artery with no collateral network. Performing the aortic revascularization simultaneously with the cholecystectomy might prevent this possible fatal outcome. CONCLUSION: This case reinforces aortic and visceral occlusive disease as a possible risk factor for the development of AAC, and discusses the treatment controversies when managing both conditions simultaneously. PMID- 27394395 TI - Right atrial thrombus and massive pulmonary embolism refractory to thrombolytic therapy: A case report. AB - INTRODUCTION: Unsuccessful thrombolysis in the setting of massive pulmonary embolism confers poor prognosis and the optimal management strategy is unknown. Options include re-thrombolysis and embolectomy. PRESENTATION OF CASE: A 32-year old lady presented with massive pulmonary embolism accompanied by an intermittently-obstructive right atrial thrombus. Failure to improve with thrombolytic therapy prompted transfer to our cardiothoracic unit for emergency surgical embolectomy. The procedure and postoperative course were without complications and the patient made a complete recovery. DISCUSSION: Contemporary data has favoured thrombolytic therapies over surgical embolectomy as the initial management strategy in massive pulmonary embolism. This case is a timely reminder of the role that surgery retains in the management of these critically ill patients, particularly when cases are complicated. We illustrate the importance of rescue surgical embolectomy in the management of massive pulmonary embolism following unsuccessful thrombolysis. In addition, we briefly review other scenarios in the management of massive pulmonary embolism where lower threshold for surgical intervention is warranted. CONCLUSION: Although current data are insufficient to direct a high level of evidence-based care, this case report and others highlight the feasibility and safety of surgical embolectomy in complicated cases of massive pulmonary embolism. PMID- 27394396 TI - Esophageal remnant cancer 35 years after acidic caustic injury: A case report. AB - INTRODUCTION: Esophageal squamous cell carcinoma has been described as a long term consequence following ingestion of corrosive substances. PRESENTATION OF CASE: We report a rare case of a 62-year-old female patient with a history of acidic caustic injury 35 years ago, for which she had undergone near total esophagogastrectomy with right colon interposition. Recently, she presented with worsening dysphagia, weight loss, neck swelling and chest pain. After the diagnostic workup, an invasive squamous cell carcinoma of the esophagus was confirmed. To our knowledge, this is the first such report in the literature. DISCUSSION: The risk for esophageal carcinoma increases substantially after ingestion of caustic substances. It is notable that distinct patterns of carcinogenesis between acids and alkalis may be postulated, since the corresponding pathophysiological impact of each one differ significantly. Although such esophageal cancers tend to have good prognosis due to early detection, both the diagnostic and therapeutic strategy may be challenging due to the limited available data in this field. Surgical treatment does not seem to eliminate the risk of cancer, as evident upon the present case report. CONCLUSION: Optimal management of esophageal corrosive injuries remains a debatable issue in terms of choosing between conservative therapy and surgical intervention. For this reason, the need for long-term follow up regardless the ingested substance and the preferred therapeutic approach is highlighted. PMID- 27394397 TI - Recurrence of an inguinal hernia containing the dome of the bladder following laparoscopic repair with mesh: A case report. AB - INTRODUCTION: A sliding hernia is a rare type of inguinal hernia in which the hernia sac is partially formed by the wall of a viscus, such as the sigmoid colon, bladder, cecum, or appendix. Sliding hernias involving the bladder often present with obstructive urinary symptoms that could potential lead to serious complications. CASE PRESENTATION: In this case, we present a 37-year-old male with a recurrent sliding hernia containing the dome of the bladder after prior laparoscopic repair of a direct inguinal hernia with mesh. DISCUSSION: A TAPP approach is preferred over a TEP approach in the laparoscopic repair of a sliding hernia; however, an open Lichenstein repair should be used in cases of recurrent hernias with severe complications, such as extensive adhesions or incarceration. CONCLUSION: The surgical approach for repair of a sliding hernia must be individualized based on the patient's clinical presentation and diagnostic findings. PMID- 27394398 TI - Neural basis of pedophilia: Altered sexual preference following traumatic brain injury. PMID- 27394399 TI - 4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites. AB - Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4 aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax. PMID- 27394400 TI - Commentary for: Facial rejuvenation via the sequential combined use of multiple laser modalities: Safety and efficacy. PMID- 27394401 TI - De-escalation versus continuation of empirical antimicrobial therapy in community acquired pneumonia. AB - OBJECTIVES: To compare mortality between de-escalation and continued empirical treatment in patients with community-acquired pneumonia. METHODS: Using a nationwide administrative database, we identified adult patients with community acquired pneumonia caused by Streptococcus pneumoniae, other streptococci, Haemophilus influenzae, Klebsiella pneumoniae, or Escherichia coli (n = 10,231) or of unknown etiology (n = 8247), discharged between July 2010 and March 2013. De-escalation was determined by the spectrum and number of antimicrobials at day 4. We used propensity score matching to obtain 489 pairs of de-escalation and continuation groups among pathogen-identified patients and 278 pairs among culture-negative patients to compare mortalities. RESULTS: In the pathogen identified patients, de-escalation was noninferior to continuation in 15-day mortality [5.3% in de-escalation versus 4.3% in continuation, a difference of 1.0% (95% confidence interval, -1.7% to 3.7%)] and in-hospital mortality [8.0% in de-escalation versus 8.8% in continuation, a difference of -0.8% (95% confidence interval, -4.3% to 2.7%)]. In the culture-negative cases, de-escalation was noninferior to continuation in terms of 15-day mortality but not in terms of in hospital mortality. CONCLUSIONS: Among patients with community-acquired pneumonia of specific etiology, de-escalation was noninferior to continuation of empirical treatment, suggesting that de-escalation is a safe strategy and supporting current recommendations. Safety of de-escalation in culture-negative cases is questionable. PMID- 27394402 TI - The burden of mucormycosis in HIV-infected patients: A systematic review. AB - OBJECTIVES: Mucormycosis is an invasive fungal infection afflicting immunocompromised patients, causing a significant degree of morbidity and mortality. The purpose of the study was to provide a comprehensive analysis describing the epidemiology and outcome of mucormycosis in the scenario of HIV infection. METHODS: We systematically searched PubMed for reports about mucormycosis associated with HIV. Eligible studies describe the predisposing factor, clinical form, treatment, and survival outcome. RESULTS: We included 61 articles from 212 reviewed abstracts, corresponding to 67 cases. Patients were mostly men (68.2%) with a median CD4(+) count of 47 [IQR 17-100] cells/mm(3). Intravenous drug use (50%), neutropenia (29.7%) and corticosteroid use (25%) were the predominant associated factors. The main clinical forms were disseminated (20.9%), renal (19.4%), and rhino-cerebral (17.9%). Rhizopus (45.5%) and Lichtheimia spp (30.3%) were the main fungal isolates. Treatment consisted of antifungal therapy and surgery in 38.8%. Overall mortality rate was 52.2%, and varied with the site of infection: 92.9% for disseminated disease, 62.5% for cerebral disease, 60% for pulmonary infection, and 36.4% for cutaneous infection. Survival was worse for those who did not initiate antifungals (p = .04), who were antiretroviral naive (p = .01), who were admitted to ICU (p = .003) or had disseminated disease (p = .007). CONCLUSIONS: Mucormycosis is a life-threatening infection in HIV patients and clinician should be aware of this co-infection in the differential diagnosis of HIV opportunistic infections. PMID- 27394403 TI - Limited value of whole blood Xpert((r)) MTB/RIF for diagnosing tuberculosis in children. AB - OBJECTIVES: We evaluated the ability of the Xpert((r)) MTB/RIF assay to detect Mycobacterium tuberculosis in whole blood of children with tuberculosis in tuberculosis endemic settings with high rates of HIV infection. METHODS: From June 2011 to September 2012 we prospectively enrolled children with symptoms or signs suggestive of tuberculosis at three research centres in Tanzania and Uganda. After clinical assessment, respiratory specimens were collected for microscopy and culture, as well as whole blood for Xpert((r)) MTB/RIF. Children were classified according to standardised case definitions. RESULTS: A total of 232 children were evaluated; 14 (6.0%) had culture-confirmed tuberculosis. The Xpert((r)) MTB/RIF assay detected M. tuberculosis in 5/232 (2.2%) blood samples with 1 (0.4%) error reading and presumably 1 (0.4%) false-positive result. The sensitivity of the assay in children with culture-confirmed (1/14) versus no tuberculosis (1/117) was 7.1% (95% CI, 1.3-31.5). Three of the five Xpert((r)) MTB/RIF positive patients had negative cultures, but were classified as probable tuberculosis cases. Assay sensitivity against a composite reference standard (culture-confirmed, highly probable or probable tuberculosis) was 5.4% (95% CI, 2.1-13.1). CONCLUSION: Whole blood Xpert((r)) MTB/RIF demonstrated very poor sensitivity, although it may enhance the diagnostic yield in select cases, with culture-negative tuberculosis. PMID- 27394404 TI - Randomized trial of micafungin versus fluconazole as prophylaxis against invasive fungal infections in hematopoietic stem cell transplant recipients. AB - OBJECTIVES: Invasive fungal infections (IFIs) cause significant morbidity and mortality among recipients of hematopoietic stem cell transplantation (HSCT). Although fluconazole is used widely as an antifungal prophylactic agent in these patients, it is not reliably effective against mold infection including invasive aspergillosis. Micafungin provides antifungal activity against Candida and Aspergillus species, and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients. Here, we evaluated and compared the incidence of proven or probable IFIs after antifungal prophylaxis using micafungin or fluconazole. METHODS: This was a prospective, single-center, phase II study involving adult patients who received allogeneic or autologous HSCT. Patients were randomly assigned to micafungin or fluconazole arms in a ratio of 2:1, and the treatment was initiated within 24 h of HSCT and maintained for up to 21 days. The primary end point was the incidence of proven or probable IFIs during the 100 days after HSCT. The secondary end points were the incidence rates of possible, proven, or probable IFIs, need to change the antifungal agent before engraftment, IFI-related mortality, and survival within 100 days after transplantation. RESULTS: Between March 2010 and May 2015, a total of 257 patients were enrolled. After exclusion of seven patients who did not receive at least one dose of a study treatment, 250 patients (micafungin, n = 165; fluconazole, n = 85) were included in the analysis of clinical efficacy. The median age was 47 years (range, 20-64). Allogeneic and autologous transplantations were performed in 56.0% (n = 140) and 44.0% (n = 110) of the patients, respectively. Baseline characteristics were well balanced between the two groups. Overall, the incidence of proven and probable IFIs within 100 days of HSCT was 7.6% (n = 19). The percentages of patients who experienced proven or probable IFIs did not differ significantly between the micafungin and fluconazole groups: 7.3% and 8.2%, respectively (p = 0.786). Thirteen patients in the micafungin arm (7.9%) and eight patients in the fluconazole arm (9.4%) needed a change in antifungal agent before engraftment (p = 0.824). Mortality within 100 days after HSCT did not differ significantly between groups: 9.1% vs 12.9% in the micafungin and fluconazole arms, respectively (p = 0.345). CONCLUSION: Micafungin is comparable to fluconazole for the prevention of IFIs in HSCT recipients. PMID- 27394405 TI - Scabies among the French armed forces in 2015. PMID- 27394406 TI - Multimodal analgesia: A systematic review of local NSAIDs for non-ophthalmologic postoperative pain management. AB - INTRODUCTION: While the analgesic benefits of systemically administered non steroidal anti-inflammatory drugs (NSAIDs) for postoperative pain are well established, benefits of locally administered NSAIDs remain unclear outside the field of ophthalmologic surgery. Studies of local NSAID administration for postoperative analgesia vary considerably in terms of dosing and methodologic quality, making it difficult to derive clinically useful information. The primary objective of this systematic review is to summarize the currently available literature in order to assess the value of local NSAIDs as a component of the multimodal postoperative pain management regimen. METHODS: A comprehensive search of PubMed and CENTRAL identified twelve randomized controlled trials comparing the use of local NSAIDs to systemic NSAIDs and/or placebo for postoperative multimodal pain management in patients undergoing non-ophthalmologic surgery. Nine trials met eligibility criteria (n = 532); each trial was classified into a subgroup based on time of NSAID administration (pre- or postoperatively) and comparison group (systemic NSAID or placebo). A frequency analysis was performed for similar outcomes reported in two or more studies. The risk of bias for each outcome and quality of evidence were assessed utilizing the Cochrane Risk of Bias instrument and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, respectively. RESULTS: Low to moderate quality evidence exists indicating that pre- or postoperative administration of local NSAIDs may provide adequate postoperative analgesia within a multimodal regimen. Additional across-study analysis reveals clinically important but non statistically significant trends towards a decreased use of additional analgesics during the postoperative period. The risk of adverse effects secondary to local NSAID administration is low. CONCLUSIONS: Local NSAIDs may be effective agents in the multimodal postoperative analgesia regimen. However, small sample size and methodologic variability across trials limits power and generalizability of outcomes. Further high quality studies are required. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42016038464. PMID- 27394407 TI - Ratio of intra-operative fluid to anesthesia time and its impact on short term perioperative outcomes following gastrectomy for cancer: A retrospective cohort study. AB - BACKGROUND: This study evaluates the short-term impact of fluid administration during gastrectomy for cancer. METHODS: A multi-institutional database of patients undergoing gastrectomy for cancer from three tertiary centers was reviewed. Logistic and linear regression analyses were performed. RESULTS: 205 patients were included. The majority of patients (n = 116, 57%) underwent proximal or total gastrectomy. Median anesthesia time was 280 min (range 95-691 min). Median intraoperative crystalloid administration was 2901 ml (range 500 10,700 ml). Median colloid administration was 0 (range 0-3835 ml), although only 66 patients (32%) received colloid. On multivariate analysis, patients who received <10.0 ml total fluid per minute of anesthesia had a significantly higher risk of complications (OR 4.12, p = 0.010). Crystalloid and total fluid administration ratios did not significantly affect LOS or discharge disposition. CONCLUSIONS: Restricting intra-operative fluid resuscitation to <10 ml total fluid per minute anesthesia is associated with an increased risk of complications in patients undergoing gastrectomy for cancer. PMID- 27394408 TI - How Well Do Stroke Risk Scores Predict Hemorrhage in Patients With Atrial Fibrillation? AB - The decision to use anticoagulants for atrial fibrillation depends on comparing a patient's estimated risk of stroke to their bleeding risk. Several of the risk factors in the stroke risk schemes overlap with hemorrhage risk. We compared how well 2 stroke risk scores (CHADS2 and CHA2DS2-VASc) and 2 hemorrhage risk scores (the ATRIA bleeding score and the HAS-BLED score) predicted major hemorrhage on and off warfarin in a cohort of 13,559 community-dwelling adults with AF. Over a cumulative 64,741 person-years of follow-up, we identified a total of 777 incident major hemorrhage events. The ATRIA bleeding score had the highest predictive ability of all the scores in patients on warfarin (c-index of 0.74 [0.72 to 0.76] compared with 0.65 [0.62 to 0.67] for CHADS2, 0.65 [0.62 to 0.67] for CHA2DS2-VASc, and 0.64 [0.61 to 0.66] for HAS-BLED) and in those off warfarin (0.77 [0.74 to 0.79] compared with 0.67 [0.64 to 0.71] for CHADS2, 0.67 [0.64 to 0.70] for CHA2DS2-VASc, and 0.68 [0.65 to 0.71] for HAS-BLED). In conclusion, although CHADS2 and CHA2DS2-VASc stroke scores were better at predicting hemorrhage than chance alone, they were inferior to the ATRIA bleeding score. Our study supports the use of dedicated hemorrhage risk stratification tools to predict major hemorrhage in atrial fibrillation. PMID- 27394409 TI - Association Between Heart Rate at Rest and Incident Atrial Fibrillation (from the Copenhagen Electrocardiographic Study). AB - Heart rate (HR) at rest is a well-known marker of cardiovascular morbidity and mortality. Results on the association between HR and incident atrial fibrillation (AF) have, however, been conflicting. Using digital electrocardiograms from 281,451 primary care patients, we aimed to describe the association between HR at rest and the hazards of incident AF. Secondary end points were death from all causes and pacemaker implantation. Data on drug use, co-morbidity, and outcomes were collected from nationwide administrative health care registries. During a median follow-up time of 8.4 years, 15,666 subjects were observed to develop AF, of which 1,631 were lone AF. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.16 (95% CI 1.06 to 1.27) for AF compared with the reference group (66 to 72 beats/min). From 72 beats/min and upward, the hazard ratio of AF increased in a dose-response manner, reaching an adjusted hazard ratio of 1.36 (95% CI 1.26 to 1.46) for HR between 95 and 120 beats/min. Both for low and high HR, the associations were accentuated for the outcome lone AF (adjusted hazard ratios of 1.48, 95% CI 1.19 to 1.84 and 1.84, 95% CI 1.47 to 2.30 for HR between 30 to 51 and 95 to 120 beats/min, respectively). For death from all causes, the hazard increased almost linearly with increasing HR. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.80 (95% CI 1.46 to 2.21) for pacemaker implantation. In conclusion, a U-shaped association was found between HR at rest and incident AF, and this association was strongest for the outcome lone AF. PMID- 27394410 TI - Impact of Early Coronary Revascularization on Long-Term Outcomes in Patients With Myocardial Ischemia on Dobutamine Stress Echocardiography. AB - The role of early coronary revascularization in the management of stable coronary artery disease remains controversial. The aim of this study was to evaluate the impact of early coronary revascularization on long-term outcomes (>10 years) after an ischemic dobutamine stress echocardiography (DSE) in patients with known or suspected coronary artery disease. Patients without stress-induced ischemia on DSE and those who underwent late coronary revascularization (>90 days after DSE) were excluded. The final study cohort consisted of 905 patients. A DSE with a peak wall motion score index of 1.1 to 1.7 was considered mild to moderately abnormal (n = 460), and >1.7 was markedly abnormal (n = 445). End points were all cause and cardiac mortality. The impact of early coronary revascularization on outcomes was assessed using Kaplan-Meier survival analysis and Cox's proportional hazard regression models. Early coronary revascularization was performed in 222 patients (percutaneous coronary intervention in 113 [51%] and coronary artery bypass grafting in 109 patients [49%]). During a median follow-up time of 10 years (range 8 to 15), 474 deaths (52%) occurred, of which were 241 (51%) due to cardiac causes. Kaplan-Meier survival curves showed that both in patients with a markedly abnormal DSE and a mild-to-moderately abnormal DSE, early revascularization was associated with better long-term outcomes. Multivariable analyses revealed that early revascularization had a beneficial effect on all cause mortality (hazard ratio 0.60, 95% confidence interval 0.46 to 0.79) and cardiac mortality (hazard ratio 0.49, 95% confidence interval 0.34 to 0.72). In conclusion, early coronary revascularization has a beneficial impact on long-term outcomes in patients with myocardial ischemia on DSE. Early coronary revascularization was associated with better outcomes not only in patients with a markedly abnormal DSE but also in those with a mild to moderately abnormal DSE. PMID- 27394411 TI - Meta-Analysis of Prognostic Implications of Exercise-Induced Ventricular Premature Complexes in the General Population. AB - Ventricular premature complexes (VPCs) during stress testing in the general population are commonly seen in clinical practice, but their prognostic value is not well understood. A comprehensive literature search of MEDLINE, Embase, and the Cochrane Library from January 1970 to May 2015 was conducted. Observational cohort studies on general populations evaluating the association between exercise induced VPCs and all-cause or cardiovascular mortality were included in the analysis. Nine studies comprising 62,488 participants comparing clinical outcomes of patients with and without exercise-induced VPCs were included. The overall combined relative risks (RRs) for all-cause mortality and cardiovascular mortality in patients with exercise-induced VPCs were 1.41 (95% CI 1.23 to 1.61) and 1.86 (95% CI 1.51 to 2.30), respectively. In subgroup analysis, both frequent VPCs (RR 1.35, 95% CI 1.14 to 1.60) and infrequent VPCs (RR 1.57, 95% CI 1.13 to 2.18) were associated with an adverse outcome. VPCs during recovery were associated with an increased risk of death (RR 1.55, 95% CI 1.22 to 1.96). VPCs during exercise did not achieve statistical significance (RR 1.14, 95% CI 0.96 to 1.34), but only a few studies were included in the analysis. In conclusion, our meta-analysis suggests that exercise-induced VPCs in the general population significantly increase the risk of total mortality and cardiovascular mortality. Our study calls for further studies to assess the prognostic significance of exercise-induced VPCs and the utility of efforts to reduce the VPC burden to improve the clinical outcome. PMID- 27394412 TI - Usefulness of the Baseline Syntax Score to Predict 3-Year Outcome After Complete Revascularization by Percutaneous Coronary Intervention. AB - Although we strive to achieve complete revascularization (CR) in those receiving percutaneous coronary intervention, it is uncertain which of these patients are at increased risk of clinical events. In this study, we aimed to investigate whether the baseline SYNTAX score (bSS) can predict adverse clinical events in patients receiving CR. From the Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting registry, the 3-year patient-oriented composite end point (POCE; all cause death, any myocardial infarction, and any revascularization) was compared according to bSS tertiles (1 <= low bSS < 6, 6 <= mid-bSS < 10, high bSS >= 10). Of the 5,088 patients, CR was achieved in 2,173 by percutaneous coronary intervention. The 3-year POCE increased significantly along with bSS tertile (7.3% vs 8.4% vs 14.8%, p <0.001). Multivariate analysis showed that, despite having the same residual SS of 0, the bSS was an independent predictor of 3-year POCE (hazard ratio 1.038, 95% confidence interval 1.018 to 1.058, p <0.001 per bSS point). In subgroup analysis, bSS was a predictor for 3 year POCE in multivessel diseases (hazard ratio 1.029, 95% confidence interval 1.004 to 1.054, p = 0.025 per bSS point), whereas in single-vessel diseases, the discriminative value of bSS was less significant. Also the clinical SYNTAX score, which added age, creatinine level, and ejection fraction to the bSS, was superior to the bSS in predicting 3-year POCE (area under the curve 0.595 vs 0.649, p = 0.008). In conclusion, the bSS was an independent predictor of long-term clinical outcomes in patients receiving CR, especially in those with multivessel coronary artery disease. Adding clinical factors to the bSS could increase the predictive power of clinical outcomes. PMID- 27394413 TI - Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress. AB - : We recently reported that stressed adipocytes release extracellular vesicles (EVs) that act as "find-me" signals to promote macrophage migration and activation. In this study, we performed a comprehensive characterization of stressed adipocyte-derived EVs, assessing their antigenic composition, lipidomics, and RNA profiles. Perilipin A was identified as one of the adipose specific proteins and studied as a potential novel biomarker to detect adipocyte derived EVs in circulation. Circulating EVs were significantly increased in mice with diet-induced obesity (DIO) and in obese humans with metabolic syndrome compared to lean controls. This increase was associated with decreased glucose tolerance in the DIO mice and metabolic dysfunction, elevated insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in the obese humans. EVs from both DIO mice and obese humans were enriched in perilipin A, a central gatekeeper of the adipocyte lipid storehouse and a marker of adipocyte differentiation. In obese humans, circulating levels of EVs enriched in perilipin A were dynamic, decreasing 35 % (p < 0.05) after a 3-month reduced calorie diet intervention. This translational study provides an extensive characterization of adipocyte-derived EVs. The findings identify perilipin A as a novel biomarker of circulating EVs of adipocyte origin and support the development of circulating perilipin A-positive EVs as indicators of adipose tissue health. KEY MESSAGE: * Extensive characterization of 3T3L1 EVs identified perilipin A in their composition. * Circulating EVs are elevated in obese mice and associated with glucose intolerance. * Circulating EVs are elevated in obese human and correlated with metabolic factors. * Perilipin A and EV levels are increased in the circulation of obese mice and human. * Circulating EV and perilipin A levels decrease with low calorie intervention. PMID- 27394414 TI - Cost and health care resource use associated with noncompliance with oral bisphosphonate therapy: an analysis using Danish health registries. AB - : We estimated the rate of compliance with oral bisphosphonates among Danish women and examined its association with health care resource use and cost. Approximately 30 % of Danish females aged >55 who take bisphosphonates are noncompliant, and noncompliance is significantly associated with increased health care resource use and cost. INTRODUCTION: Two objectives of this study were to estimate the rate of oral bisphosphonate compliance among Danish women and to examine the association of noncompliance with health care resource use and cost. METHODS: Women >=55 with an index prescription claim for an oral bisphosphonate were identified from Danish national health registries between 2003 and 2008. Compliance was measured as the medication possession ratio (MPR) during the first 12 months post-index. Cost and health care resource use were collected for the following 12 months. RESULTS: Among the 38,234 women meeting the study inclusion criteria, 29.9 % were noncompliant (MPR <70 %). Younger age was associated with higher odds of compliance (OR [95 % CI] 1.22 [1.15-1.29] for ages 55-64 and 1.18 [1.12-1.24] for ages 65-74; reference age group >=75 years). Rates of all-cause health care resource use were significantly higher in noncompliant subjects: 28.9 versus 23.0 % had inpatient admissions, 16.5 versus 13.0 % had emergency room visits, and 48.7 versus 43.3 % used outpatient services (P < 0.001 for all comparisons). The total mean (SD) all-cause cost per patient (excluding office visits) was ?626 (2344) and ?4178 (7854), respectively. The mean (SD) osteoporosis-related cost per patient (excluding office visits) was ?572 (2085) and ?754 (2857) for compliant and non-compliant subjects, respectively. The compliant subjects accrued significantly lower all-cause and OP-related cost than noncompliant subjects, regardless of whether the total cost or medical cost only was considered. CONCLUSIONS: Approximately 30 % of Danish females aged 55 or older who take bisphosphonates are noncompliant. Noncompliance is significantly associated with increased health care resource use and cost. PMID- 27394415 TI - Strength measures are better than muscle mass measures in predicting health related outcomes in older people: time to abandon the term sarcopenia? AB - : There is no clear consensus on definition, cut-points or standardised assessments of sarcopenia. We found a lower limb strength assessment was at least as effective in predicting balance, mobility and falls in 419 older people as muscle mass-based measures of sarcopenia. INTRODUCTION: There is currently no consensus on the definition, cut-points or standardised assessments of sarcopenia. This study aimed to investigate whether several published definitions of sarcopenia differentiate between older people with respect to important functional and health outcomes. METHODS: Four hundred nineteen community-living older adults (mean age 81.2 +/- 4.5, 49 % female) completed assessments of body composition (dual-energy X-ray absorptiometry), strength, balance, mobility and disability. Falls were recorded prospectively for a year using monthly calendars. Sarcopenia was defined according to four skeletal mass-based definitions, two strength-based definitions (handgrip or knee extensor force) and a consensus algorithm (low mass and low strength or slow gait speed). Obesity was defined according to percentage fat mass or waist circumference. RESULTS: The four skeletal mass-based definitions varied considerably with respect to the percentage of participants classified as sarcopenic and their predictive accuracy for functional and health outcomes. The knee extension strength-based definition was equivalent to or better than the mass-based and consensus algorithm definitions; i.e. weaker participants performed poorly in tests of leaning balance, stepping reaction time, gait speed and mobility. They also had higher physiological fall risk scores and were 43 % more likely to fall at home than their stronger counterparts. Adding obesity to sarcopenia definitions identified participants with greater self-reported disability. CONCLUSIONS: A simple lower limb strength assessment was at least as effective in predicting balance, functional mobility and falls in older people as more expensive and time consuming muscle mass-based measures. These findings imply that functional terms such as muscle weakness or motor impairment are preferable to sarcopenia. PMID- 27394416 TI - SMS regulates the expression and function of P-gp and MRP2 in Caco-2 cells. AB - Sphingomyelin synthase (SMS) has two isoforms of SMS1 and SMS2, the last enzyme involved in the biosynthesis of sphingomyelin (SM), and has impact on the expression of membrane proteins. In the present study, we explored the potential effects of SMS on drug transporters, a special family of membrane proteins in human intestinal epithelial Caco-2 cells. The specific knockdown of SMS1 or SMS2 with siRNA in Caco-2 cells substantially decreased the expression and function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2) rather than other drug transporters MRP1, MRP3, PEPT1, OATP2B1, and BCRP. In the SMS1 stable overexpressed Caco-2 cell line, the expression levels of P-gp and MRP2 and transcription factor pregnane X receptor (PXR) were upregulated and the phosphorylation levels of signaling pathways janus protein tyrosine kinase 2 (JAK 2) and extracellular signal-regulated kinases (ERK) were also evidently increased; however, the upregulated mRNA expression levels of PXR, P-gp, and MRP2 were diminished by inhibiting the phosphorylation of ERK and JAK-2. Furthermore, the SMS1 overexpression in Caco-2 cells altered the expression levels of ERM proteins ezrin and moesin, which are closely connected to the function of drug transporters. In conclusion, we herein demonstrate for the first time that in Caco-2 cells SMS regulates the expression and function of drug transporters P-gp and MRP2, and their regulator PXR is mediated by phosphorylated ERK and JAK-2 signaling pathways. PMID- 27394417 TI - Neuroprotective Effect of the LRRK2 Kinase Inhibitor PF-06447475 in Human Nerve Like Differentiated Cells Exposed to Oxidative Stress Stimuli: Implications for Parkinson's Disease. AB - Leucine-rich repeat kinase 2 (LRRK2) has been implicated in oxidative stress (OS) and neurodegeneration in Parkinson's disease (PD). However, the pathophysiological mechanism of the LRRK2 kinase in neurons under stress stimuli is not yet understood. We demonstrate that rotenone (ROT), a mitochondria complex I inhibitor frequently used to generate in vitro and in vivo experimental models of PD, induces LRRK2 phosphorylation at serine 935 p-(S935) concomitant with cell death in nerve-like differentiated cells (NLCs). Indeed, ROT (50 uM) at 6 h exposure significantly increased reactive oxygen species (ROS) (~100 %), p-(S935) LRRK2 kinase [~2 f(old)-(i)ncrease] level, induced nuclei condensation/fragmentation (16 %), increased the expression of NF-kappaB (5.6 f i), p53 (5.3 f-i), c-Jun (5.4 f-i) transcription factors, activated caspase-3 (8.0 f-i) and AIF (6.8 f-i) proteins; but significantly decreased mitochondrial membrane potential (?Psim, ~21 %), indicative of apoptosis -a type of regulated cell death process- compared to untreated cells. Strikingly, the LRRK2 kinase inhibitor PF-06447475 (PF-475, 1 uM) protects NLCs against ROT induced noxious effect. The inhibitor not only blocked the p-(S935)-LRRK2 kinase phosphorylation but also completely abolished ROS, and significantly reversed all ROT-induced apoptosis signaling and OS associated markers to comparable control values. We conclude that wild-type LRRK2 may act as a pro-apoptotic factor under OS stimuli. Our findings suggest an association between OS and LRRK2 phosphorylation in the NLCs death process, as PD model. Therefore, the pharmacological inhibition of LRRK2 might help to understand the OS-mediated kinase activation in PD neurodegenerative disorder. PMID- 27394418 TI - Fucoxanthin Activates Apoptosis via Inhibition of PI3K/Akt/mTOR Pathway and Suppresses Invasion and Migration by Restriction of p38-MMP-2/9 Pathway in Human Glioblastoma Cells. AB - Fucoxanthin is rich in seaweed and considered as effective anti-cancer drug because of powerful antioxidant properties. The objective of this study was to investigate the role of fucoxanthin on apoptosis, invasion and migration of glioma cells. Firstly, fucoxanthin showed obvious cytotoxicity against human glioma cancer cell line U87 and U251, however, there was no inhibitory effect on normal neuron. And then, fucoxanthin induced apoptotic cell death showed by the condensation of chromatin material stained with Hoechest 33342, and reduced mitochondrial membrane potential via DIOC6(3) staining, and enhanced apoptosis by annexin V-FITC/SYTOX Green double staining on U87 and U251 cell lines. Transmission electron microscopy and western blotting were used to determine ultrastructure of U87 cell and expression of proteins related to apoptosis. A scratch wound healing assay and the expression of matrix metalloproteinases (MMPs), and a tans-well assay were used to investigate cell migration and invasion, respectively. Additionally, we uncovered upstream signaling Akt/mTOR and p38 pathways induced by incubation U87 and U251 cell lines with fucoxanthin that mediated cell apoptosis, migration and invasion by using PI3K and p38 inhibitors. Moreover, incubation of fucoxanthin obviously reduced the weight and volume of glioma mass of U87 cells in nude mice. Furthermore, we also examined the glioma mass of U87 cells by hematoxylin-eosin staining, TUNEL assay and western blot, and these outcomes in vivo consistently confirmed that above results in vitro. Taken together, these findings suggest that fucoxanthin augments apoptosis, and reduces cell proliferation, migration and invasion, and reveals a potential mechanism of fucoxanthin-mediated Akt/mTOR and p38 susspression in human glioblastoma cell line. PMID- 27394419 TI - Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro. AB - Oligodendroglial cells are known to de-acetylate the N-acetylaspartate (NAA) synthesized and released by neurons and use it for lipid synthesis. However, the role of NAA regarding their intermediary metabolism remains poorly understood. Two hypotheses were proposed regarding the fate of aspartate after being released by de-acetylation: (1) aspartate is metabolized in the mitochondria of oligodendrocyte lineage cells; (2) aspartate is released to the medium. We report here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture. Moreover, characterising metabolic functions of acetyl coenzyme A and aspartate from NAA catabolism in mature oligodendrocyte cultures after 5 days using isotope-labelled glucose after 5-days of differentiation we found evidence of extensive NAA metabolism. Incubation with [1,6-13C]glucose followed by gas chromatography-mass spectrometry and high performance liquid chromatography analyses of cell extracts and media in the presence and absence of NAA established that the acetate moiety produced by hydrolysis of NAA does not enter mitochondrial metabolism in the form of acetyl coenzyme A. We also resolved the controversy concerning the possible release of aspartate to the medium: aspartate is not released to the medium by oligodendrocytes in amounts detectable by our methods. Therefore we propose that: aspartate released from NAA joins the cytosolic aspartate pool rapidly and takes part in the malate-aspartate shuttle, which transports reducing equivalents from glycolysis into the mitochondria for ATP production and enters the tricarboxylic acid cycle at a slow rate. PMID- 27394420 TI - Phytodesalinization potential of Typha angustifolia, Juncus maritimus, and Eleocharis palustris for removal of de-icing salts from runoff water. AB - Typha angustifolia, Juncus maritimus, and Eleocharis palustris were evaluated for de-icing salt removal from runoff water. Plants were exposed to a range of de icing salt levels (0.2, 0.7, 4, 8, and 13 dS m(-1)) in laboratory-scale subsurface constructed wetlands (CWs) for 2 months under greenhouse conditions. Effluent characteristics, plant height, biomass, and Cl and Na removal rates and uptake were monitored. More water volume was retained in CWs of T. angustifolia (~60 %) than of J. maritimus and E. palustris (~37.5 %), which accounted for the electrical conductivity increase in effluents (1.3-1.9-fold). Based on the NaCl removal rate, T. angustifolia showed the greatest phytodesalinization ability (31 60 %) with the highest removal at the lowest salt levels (0.2-0.7 dS m(-1)), followed by J. maritimus (22-36 %) without differences in removal among levels, and E. palustris (3-26 %) presenting a removal rate highly decreased with increasing salt levels. Plant height and biomass were stimulated at low de-icing salt levels, but, at higher levels, T. angustifolia and E. palustris growth was inhibited (tolerance index ~67 and 10 %, respectively, in the worst cases). Salt amounts in aboveground biomass in g m(-2) differed among levels and ranged as follows: 13.6-29.1 (Cl), 4.2-9.3 (Na; T. angustifolia); 7.0-12.0 (Cl), 2.7-6.4 (Na; J. maritimus); and 0.9-7.6 (Cl), 0.3-1.6 (Na; E. palustris). Chloride and Na translocation decreased with de-icing salt increase in T. angustifolia, while no significant differences were found in J. maritimus, which is interesting for harvesting purposes. PMID- 27394421 TI - Source and long-term behavior of transuranic aerosols in the WIPP environment. AB - Source and long-term behavior transuranic aerosols ((239+240)Pu, (238)Pu, and (241)Am) in the ambient air samples collected at and near the Waste Isolation Pilot Plant (WIPP) deep geologic repository site were investigated using historical data from an independent monitoring program conducted by the Carlsbad Environmental Monitoring and Research Center and an oversight monitoring program conducted by the management and operating contractor for WIPP at and near the facility. An analysis of historical data indicates frequent detections of (239+240)Pu and (241)Am, whereas (238)Pu is detected infrequently. Peaks in (239+240)Pu and (241)Am concentrations in ambient air generally occur from March to June timeframe, which is when strong and gusty winds in the area frequently give rise to blowing dust. Long-term measurements of plutonium isotopes (1985 2015) in the WIPP environment suggest that the resuspension of previously contaminated soils is likely the primary source of plutonium in the ambient air samples from WIPP and its vicinity. There is no evidence that WIPP is a source of environmental contamination that can be considered significant by any health based standard. PMID- 27394422 TI - Effects of bypass system on PCDD/F emission and chlorine circulation in cement kilns. AB - A bypass at the kiln inlet allows the effective reduction of alkali chloride cycles and thus perhaps affects the emission of PCDD/Fs. Effects of bypass system on PCDD/F emission and chlorine circulation were studied in two typical dry cement kilns with 5000 ton/day clinker capacity in China and named CK1 and CK2, respectively. Firstly, the emission level of PCDD/Fs with the operation of bypass system was estimated in CK1, to certify that bypass system has a perfect adaption to the cement kiln regarding the PCDD/F emission even with the refuse derived fuel (RDF) as the replacement of fuel. On the other hand, the operating conditions in the CK2 were scrutinised by monitoring the concentrations of SO2, NH3 and HCl. In addition, the characteristics of raw meal, clinker, bag filter ash and bypass ash were also investigated by Energy Dispersive Spectrometer (EDS), metal and chlorine analysis. The balance of chlorine showed that 18 % of the possible accumulated chlorine could be ejected from the cement kiln system when 2 % of kiln exhaust gas was extracted. Furthermore, the emission level of PCDD/Fs in the main flue gas also decreased from 0.037 +/- 0.035 ng I-TEQ/Nm(3) to 0.019 +/- 0.007 ng I-TEQ/Nm(3) with a reduction efficiency of 48.2 %. Most importantly, PCDD/F emission from the bypass system was proven to have rather minor effect on the total emission factor. The congener distributions of PCDD/Fs were also analysed in the flue gas and fly ash, before and after application of bypass system, to find cues to the formation mechanism. PMID- 27394423 TI - The plasma levels of brain-derived neurotrophic factor are positively associated with emergence agitation in the elderly after gastrointestinal surgery. AB - AIMS: To explore the association between plasma concentrations of brain-derived neurotrophic factor (BDNF) and the occurrence of emergence agitation (EA) in the elderly after gastrointestinal surgery. METHODS: Seventy-two patients were recruited, who received gastrointestinal surgery and general anesthesia. BDNF level of blood was detected by ELISA before anesthesia (baseline), 10 min after tracheal intubation before the start of surgery, at skin closure, 10 min after tracheal extubation, and 24 h postoperatively. Patients with a Ricker Sedation Agitation Scale (RSAS) score >=5 at any time in the post anesthesia care unit were considered to have emergence agitation. RESULTS: The incidence of EA in this population was 40 % (29/72). The EA group had higher plasma BDNF levels at skin closure (497.86 +/- 69.65 vs. 307.86 +/- 51.91, p < 0.05) and especially at 10 min after tracheal extubation (900 +/- 224.6 vs. 476.28 +/- 107.15, p < 0.001). Moreover, the levels of plasma BDNF at skin closure, 10 min after tracheal extubation and postoperative pain, were positively related with RSAS scores. CONCLUSIONS: Our results suggest that plasma BDNF is associated with the occurrence of emergence agitation after gastrointestinal surgery. PMID- 27394424 TI - Myocardial Layers Specific Strain Analysis for the Acute Phase of Infant Kawasaki Disease. AB - : Recently, the prevalence of infant Kawasaki disease (KD) has increased. However, the myocardial functional analysis of infant KD can be difficult and rarely reported. The purpose of this study was to investigate layer specific myocardial strain analysis for better assessment of the acute period in infant KD. The study retrospectively reviewed the echocardiographic data of 25 infant patients with KD at the acute phase. With advanced imaging, pulsed tissue Doppler velocity data, myocardial strain with three layers specific analysis was performed. Then the data were compared with 25 age-matched healthy control infants. The measures of longitudinal strain and radial strain were decreased in infant KD compared to healthy controls. The circumferential strain was significantly decreased in infant KD at all three myocardial layers, especially in the endocardial layer (KD: -20.5 +/- 6.4 % vs. CONTROL: -25.6 +/- 7.6 %, endocardium, p = 0.00001; -14.6 +/- 4.4 % vs. -18.1 +/- 4.0 %; middle myocardium, p = 0.01; -9.7 +/- 3.3 % vs. -11.4 +/- 3.8 %; epicardium, p = 0.04). The acute phase of infant KD demonstrated decreased myocardial strain measurement. Circumferential strain was the lowest in the endocardial layer. Further continuous long-term follow up for myocardial assessment should be recommended even after recovery with appropriate treatment. PMID- 27394425 TI - Narrowing of the radicular pulp space in coronally restored teeth. AB - OBJECTIVES: Narrowed radicular pulp spaces are frequently observed in teeth wearing extended restorations. The present study investigates whether the narrowing of particularly the radicular pulp space can be attributed to coronal restorations. MATERIALS AND METHODS: The study is based on an anonymized copy of the cone-beam computed tomography (CBCT) database from the Center of Dental Medicine of the University of Zurich. One hundred CBCT scans were selected out of 7317 data sets to match either a crowned (group A; n = 50) or a filled tooth (group B; n = 50) with a contralateral healthy, unrestored, and caries-free control tooth at the same position, respectively. Cross-sectional images were adjusted in the coronal, middle, and apical root third of each subjected tooth. Screenshots were taken in that position and analyzed. The area occupied by the pulp space was determined as percentage area of the whole root diameter on each cross section. The resulting values were compared between restored and control teeth. RESULTS: In both groups (crowned and filled teeth) and in all the three root thirds, the radicular pulp space was significantly narrower in the restored teeth compared to the control teeth. The strongest narrowing effect was observed in the coronal root third and it decreased towards the apical root third (both groups). CONCLUSIONS: Teeth with coronal restorations show within the limitations of the present study a significant narrowing of their radicular pulp space. CLINICAL RELEVANCE: The asserted narrowing could have a complicating effect if root canal treatment becomes necessary in those teeth. PMID- 27394427 TI - The high correlation between counts and area fractions of lipofuscin granules, a biomarker of oxidative stress in muscular dystrophies. AB - Images of cryostat unstained sections of two skeletal muscles, diaphragm and extensor digitorum longus (EDL), from wild-type normal and dystrophic mdx mice were captured with a fluorescence microscope, binarised and analysed by an automated procedure using ImageJ free software. The numbers, Feret diameters and areas of autofluorescent lipofuscin (LF)-like granules in the sections were determined from the binary images. The mean numbers of counted LF granules per mm3 muscle tissue correlated highly (r >= 0.9) with the area fractions of the granules in sections of both normal and mdx muscles. The similar distribution patterns of granule sizes in sections of diaphragm and EDL muscles are consistent with the high correlations. PMID- 27394426 TI - Maturation of cortical bone suppresses periosteal osteoprogenitor proliferation in a paracrine manner. AB - Periosteum contains enriched pools of osteogenic progenitors and is highly proliferative, thus giving this tissue a pivotal role in maintaining the diameter of the diaphyseal cortex and in recovery from fractures. Although periosteal proliferation has not been detected in normal bone, intense periosteal proliferation has been observed in pathologic states such as fracture, inflammation, and bone tumors. However, the mechanism by which periosteal osteoprogenitor proliferation is regulated remains poorly understood. To investigate this regulation mechanism, osteoblast/osteocyte-specific conditional knockout mice were developed lacking Smad4 and Osx, two factors that are essential for osteoblast differentiation and matrix mineralization. In Smad4 (Col) and Osx (Col) mice, osteocalcin, Dmp-1, and sclerostin expression were significantly decreased in the cortical bone. Interestingly, although Cre activity was not observed in the periosteum, the proliferation of periosteal osteoprogenitors was enhanced in Smad4 (Col) and Osx (Col) mice, as assessed by 5'-bromo-2'deoxyuridine incorporation and proliferating cell nuclear antigen localization. Since Wnt signaling is a major factor affecting periosteal proliferation, we evaluated Wnt signaling in the periosteum. The expression levels of beta-catenin and Lef-1 were increased in the periosteal osteoprogenitors. Moreover, the mRNA levels of beta-catenin, cyclin D1, Lef-1, and Axin2, all of which are Wnt target genes, were significantly increased in the periosteum of both Smad4 (Col) and Osx (Col) mice. These results indicated that extracellular proteins secreted by mature osteoblasts and osteocytes suppress the proliferation of periosteal osteoprogenitors by blocking Wnt signaling in a paracrine manner. Our data suggest a new concept of periosteal bone healing and periosteal bone formation. PMID- 27394429 TI - Estimation of the physical properties of neurons and glial cells using dielectrophoresis crossover frequency. AB - We successfully determine the ranges of dielectric permittivity, cytoplasm conductivity, and specific membrane capacitance of mouse hippocampal neuronal and glial cells using dielectrophoresis (DEP) crossover frequency (CF). This methodology is based on the simulation of CF directly from the governing equation of a dielectric model of mammalian cells, as well as the measurements of DEP CFs of mammalian cells in different suspension media with different conductivities, based on a simple experimental setup. Relationships between the properties of cells and DEP CF, as demonstrated by theoretical analysis, enable the simultaneous estimation of three properties by a straightforward fitting procedure based on experimentally measured CFs. We verify the effectiveness and accuracy of this approach for primary mouse hippocampal neurons and glial cells, whose dielectric properties, previously, have not been accurately determined. The estimated neuronal properties significantly narrow the value ranges available from the literature. Additionally, the estimated glial cell properties are a valuable addition to the scarce information currently available about this type of cell. This methodology is applicable to any type of cultured cell that can be subjected to both positive and negative dielectrophoresis. PMID- 27394428 TI - Safety and efficacy of denosumab in osteoporotic hemodialysed patients. AB - BACKGROUND AND AIMS: In elderly subjects, renal insufficiency and osteoporosis often coexist with high risk of fracture and elevated socio-economic burden. Today a large number of effective anti-osteoporotic drugs are available but generally they are contraindicated in patients with chronic kidney disease (CKD) because of their progressive accumulation. Denosumab, instead, does not require dose adjustments for different degrees of renal impairment so it can be a valid treatment in osteoporotic patients with CKD. Limited data are available in the literature concerning the use of denosumab in hemodialysis (HD). The aim of our study was, therefore, to study the efficacy and tolerability of this drug in this particular subset of patients. METHODS: We retrospectively reviewed the charts of 12 osteoporotic HD patients who received a single 60-mg subcutaneous dose of denosumab every 6 months for an observation period of 24 months. Serum electrolyte, markers of bone turnover and quantitative ultrasound (QUS) were evaluated. RESULTS: Over 24 months, we observed a gradual improvement of bone metabolism: beta-CrossLaps from 2567.08 +/- 1264 to 1492.5 +/- 1182.5 pg/ml; bone alkaline phosphatase (BALP) from 33.5 +/- 28.8 to 11.8 +/- 3.7 mcg/l, and of QUS index (T-score from -5.33 +/- 1.58 to -4.84 +/- 1.2; risk of fracture from 13.9 +/- 4.7 to 11.07 +/- 5.3 %). Few cases of hypocalcemia were detected, more significant after the first and second injection, but with careful monitoring of serum calcium and rapid therapy adjustment we could easily manage serum Ca levels. CONCLUSIONS: Our pilot experience highlights the safety and efficacy of denosumab in the treatment of osteoporosis in HD patients, potentially supporting its use to reduce the burden of fractures in this patient population. PMID- 27394430 TI - Confirmatory Factor and Rasch Analyses Support a Revised 14-Item Version of the Organizational, Policies, and Practices (OPP) Scale. AB - Background The long version of the organizational, policies and practices (OPP) had a high burden and short versions were developed to solve this drawback. The 11-item version showed promise, but the ergonomic subscale was deficient. The OPP 14 was developed by adding three additional items to the ergonomics subscale. The aim of this study is to evaluate the factor structure using confirmatory factor and Rasch analyses in healthy firefighters. Methods A sample of 261 firefighters (Mean age 42 years, 95 % male) were sampled. A confirmatory factor and Rasch analyses were used to assess the internal consistency, factor structure and other psychometric characteristics of revised OPP-14. Results The OPP-14 demonstrates sound factor structure and internal consistency in firefighters. Confirmatory factor analysis confirmed the consistency of the original 4-domain structure (CFI = 0.97, TLI = 0.96, and RMSEA = 0.053). The 5 items showing misfit initially with disordered thresholds were rescored. The four subscales satisfied Rasch expectations with well target and acceptable reliability. Conclusions The OPP-14 scale shows a promising factor structure in this sample and remediated deficits found in OPP-11. This version may be preferable for musculoskeletal concerns or work applications where ergonomic indicators are relevant. PMID- 27394431 TI - Prognostic relevance of histopathological features in signet ring cell carcinoma of the colorectum. AB - Signet ring cell carcinoma (SRCC) is a rare variant of colorectal cancer (CRC), by definition composed of at least 50 % of neoplastic cells showing signet ring cell morphology. Colorectal SRCC is mainly characterized by aggressive clinical behavior, high pTNM stage and microsatellite instability (MSI). We assessed the prognostic value of several histopathological parameters (histological grade, venous invasion, lymphovascular invasion, MSI, mucin content, tumour budding, pTNM stage) in terms of disease free survival (DFS) and cancer specific survival (CSS) in a series of 32 SRCCs. We confirm that pTNM stage at diagnosis is relevant for predicting DFS and CSS in SRCC. In addition, we show on haematoxylin and eosin or immunohistochemically stained (CD34, podoplanin) sections that venous invasion and lymphovascular invasion are significantly associated with shorter DFS and CSS in SRCC. Notably, venous invasion assed by immunohistochemistry had the highest risk ratio and proved to be the only independent prognostic variable. Finally, we show that histological grade, as assessed on the percentage of formed glands, has prognostic relevance in SRCC as high-grade tumours (<50 % of glands) had significantly shorter CSS compared to low-grade tumours. This remained an independent variable at multivariate analysis. If our findings are confirmed in further studies, venous invasion as assessed by immunohistochemistry and histological Tgrade might be added to guidelines for SRCC reporting as significant prognostic factors. PMID- 27394432 TI - Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer. AB - Selected patients with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) detected on transrectal ultrasound (TRUS)-guided biopsies may be considered for active surveillance (AS); however, a proportion of these will harbor more aggressive disease. The purpose of this study was to determine if morphologies of Gleason pattern 4 PCa may predict upgrading and/or upstaging after radical prostatectomy (RP). A database search for men with GS 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy that underwent RP between January 2010 and October 2015 identified 152 patients. Two blinded genitourinary pathologists independently reviewed the biopsies and assessed ill-defined glands (IDG), fused glands, small or large cribriform patterns, and glomerulations. Patient age, serum prostate specific antigen (PSA), percentage (%) of biopsy sites involved by 3 + 4 = 7 PCa, and overall extent of pattern 4 were also recorded. GS and stage (presence or absence of extraprostatic extension [EPE]) were retrieved from RP reports. Data were compared using independent t tests and chi-square. Inter-observer agreement was calculated using Cohen's Kappa statistic. Percent of biopsy sites and extent of pattern 4 were compared to statistically significant morphologies using the Spearman correlation. 28.3 % (43/152) of patients were upgraded to GS >3 + 4 = 7 at RP (GS 4 + 3 = 7 [N = 17], GS 4 + 3 = 7 with tertiary pattern 5 [N = 25], and GS 4 + 5 = 9 [N = 1]) and 44.1 % (67/152) showed EPE after RP. PSA was associated with both upgrading (8.5 +/- 5.4 vs. 6.9 +/- 3.2 ng/mL, [p = 0.04]) and EPE (8.2 +/- 4.6 vs. 6.7 +/- 3.2 ng/mL, [p = 0.03]). IDG, fused glands, and glomerulations were not associated with upgrading or EPE (p > 0.05) with moderate to strong inter-observer agreement (K = 0.76-0.88). There was strong inter-observer agreement for small and large cribriform formations (K = 0.93 and 0.94, respectively) and both patterns were strongly associated with upgrading (p < 0.001) and EPE (p = 0.02) on RP. Strong associations were observed between increasing number of morphologies and both upgrading (p = 0.0.25) and EPE (p < 0.001). Overall extent of pattern 4 was associated with upgrading (p = 0.009) and EPE (p = 0.019) while percent of sites involved by GS 3 + 4 = 7 was only associated with EPE (p = 0.023). Cribriform morphology correlated to percentage of sites with 3 + 4 and overall extent of pattern 4 (rho = 0.25, p = 0.002, rho = 0.20, p = 0.015, respectively). Presence of cribriform morphology on TRUS-guided biopsy is strongly associated with upgrading and upstaging at RP and shows near perfect inter-observer agreement whereas IDG, fused glands, and glomerulations were not useful. Cribriform morphology may be of importance when considering treatment plans for patients with intermediate risk PCa. PMID- 27394433 TI - Infectious and Environmental Influences on the Obesity Epidemic. AB - Over the last two decades, the prevalence of obesity has increased rapidly. While it is intuitively appealing to believe that the causes of obesity are manifestly related to excess dietary intake, combined with a reduced expenditure of energy via a decrease in physical activity, it is also been noted that the evidence for these as the sole causes of the obesity epidemic is incomplete. This has led to the search for other causes of obesity, particularly those which stem from the environment we live in. This review will explore two putative causes of obesity: infections and environmental pollutants. It will focus on the key human infection associated with obesity-human adenovirus 36 (Ad36) and will discuss several environmental pollutants which have been postulated to be involved in the development of obesity: bisphenol A, phthalates and persistent organic pollutants. For each of these, the epidemiology and biological mechanisms underpinning the association of these agents with obesity will be reviewed. PMID- 27394434 TI - The effect of habitat disturbance on the abundance of nocturnal lemur species on the Masoala Peninsula, northeastern Madagascar. AB - Madagascar is one of the world's biodiversity hotspots. The island's past and current rates of deforestation and habitat disturbance threaten its plethora of endemic biodiversity. On Madagascar, tavy (slash and burn agriculture), land conversion for rice cultivation, illegal hardwood logging and bushmeat hunting are the major contributors to habitat disturbance. Understanding species-specific responses to habitat disturbance across different habitat types is crucial when designing conservation strategies. We surveyed three nocturnal lemur species in four forest types of varying habitat disturbance on the Masoala Peninsula, northeastern Madagascar. We present here updated abundance and density estimates for the Endangered Avahi mooreorum and Lepilemur scottorum, and Microcebus sp. Distance sampling surveys were conducted on 11 transects, covering a total of 33 km after repeated transect walks. We collected data on tree height, bole height, diameter at breast height, canopy cover and tree density using point-quarter sampling to characterise the four forest types (primary lowland, primary littoral, selectively logged and agricultural mosaic). Median encounter rates by forest type ranged from 1 to 1.5 individuals (ind.)/km (Microcebus sp.), 0-1 ind./km (A. mooreorum) and 0-1 ind./km (L. scottorum). Species density estimates were calculated at 232.31 ind./km2 (Microcebus sp.) and 121.21 ind./km2 (A. mooreorum), while no density estimate is provided for L. scottorum due to a small sample size. Microcebus sp. was most tolerant to habitat disturbance, exhibiting no significant effect of forest type on abundance. Its small body size, omnivorous diet and generalised locomotion appear to allow it to tolerate a variety of habitat disturbance. Both A. mooreorum and L. scottorum showed significant effects of forest type on their respective abundance. This study suggests that the specialist locomotion and diet of A. mooreorum and L. scottorum make them susceptible to the effects of increasing habitat disturbance. PMID- 27394435 TI - Myocardial blood volume reserve by intravenous contrast echocardiography predicts improvement in left ventricular function in patients with nonischemic dilated cardiomyopathy. AB - BACKGROUND: Impaired myocardial perfusion has been shown in nonischemic dilated cardiomyopathy (DCM). Intravenous myocardial contrast echocardiography (MCE) has been introduced to examine myocardial blood volume (MBV) noninvasively. This study was designed to evaluate if MBV reserve assessed by intravenous MCE with adenosine triphosphate (ATP) can predict efficacy of optimal medical therapy in patients with DCM. METHODS AND RESULTS: Fifteen DCM patients and 8 control subjects underwent conventional echocardiography and intravenous MCE. We obtained the change in peak contrast integrated backscatter intensity (?PI) by ATP on the left ventricular (LV) anteroseptal myocardium. After 3 months of optimal medical therapy in DCM patients, we reperformed conventional echocardiography. A good responder to therapy was defined as a decrease in LVDd >5 mm to final LVDd <55 mm and increase in LVEF >20 % to final LVEF >45 %. In DCM patients, ?PI was lower compared to controls (p < 0.001). Good responders to therapy (n = 6) had higher ?PI than poor responders (n = 9) (p < 0.05). CONCLUSIONS: The present study demonstrates that the response to the medical therapy in DCM is predicted by the assessment of dilator reserve in MBV. Intravenous MCE with ATP may provide useful information to evaluate MBV reserve. PMID- 27394436 TI - Gastro-esophageal Reflux Disease Associated Infantile Wheezing; Phenotype Characteristics and Effect of Antireflux Medications. PMID- 27394438 TI - Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro. AB - The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM + PRP. Significant proliferative stimulation was observed after 48 h of culture (p < 0.05) on mean absorbance of fibroblasts cultured with 10 and 25 % PRP, 100 % CM, and 25 % PRP + 25 % CM, if compared with control. Keratinocyte proliferation was stimulated after 48 h in cultures with 25, 50, and 100 % CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10 % PRP + 10 % CM after 48 h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo. PMID- 27394439 TI - Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM 3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM 3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4(+) T cells, CD8(+) T cells, CD56(+) T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM 3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3 stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-gamma, and TNF alpha), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment. PMID- 27394440 TI - Repellency to ticks (Acari: Ixodidae) of extracts of Nigella sativa (Ranunculaceae) and the anti-inflammatory DogsBestFriendTM. AB - Motivated by observations that the canine anti-inflammatory cream DogsBestFriendTM (DBF) appeared to deter flies, mosquitoes, and ticks from treated animals, repellent efficacy bioassays using four species of ticks were conducted with three extracts of Nigella sativa L. (Ranunculaceae), a constituent of DBF. The DBF cream was tested against nymphs of lone star tick, Amblyomma americanum (L.). In vertical filter paper assays, the three extracts applied at 0.413 mg extract/cm(2) filter paper repelled 96.7-100 % of brown dog tick, Rhipicephalus sanguineus (Latreille) nymphs, whereas, at the same rate, only one extract repelled >90 % A. americanum nymphs. Adult (mixed sexes) American dog ticks, Dermacentor variabilis (Say), required a higher concentration to be repelled effectively; two extracts, applied at 0.827 mg extract/cm(2) filter paper, repelled >=90 % of the D. variabilis. In contrast, all extracts applied at much lower concentration (0.206 mg extract/cm(2) filter paper) repelled 100 % adult blacklegged ticks, Ixodes scapularis Say (only females tested). Of the two more repellent extracts, one lost most of its activity against A. americanum nymphs in <4 h when applied at 0.827 mg extract/cm(2) filter paper, whereas the other repelled 66.7 % of the nymphs at 192 h after application. At 0.206 mg extract/cm(2) filter paper, one extract was as repellent as deet against A. americanum nymphs. In a vertical bioassay in which nylon organdy was substituted for filter paper, DBF, at the rates of 1.67 and 0.835 mg cream/cm(2), repelled 76.7 and 30.0 % A. americanum nymphs, respectively. These findings indicate that when applied appropriately DBF should afford some protection to canines against tick bites. PMID- 27394441 TI - Anaplasma marginale and Theileria annulata in questing ticks from Portugal. AB - Ticks are ubiquitous arthropods and vectors of several pathogenic agents in animals and humans. Monitoring questing ticks is of great importance to ascertain the occurrence of pathogens and the potential vector species, offering an insight into the risk of disease transmission in a given area. In this study 428 host seeking ticks, belonging to nine species of Ixodidae and collected from 17 of the 23 Portuguese mainland subregions, were screened for several tick-borne agents with veterinary relevance: Anaplasma marginale, Anaplasma ovis, Anaplasma centrale, Babesia spp., Coxiella burnetii and Theileria spp. Prevalence was assessed by PCR and amplified amplicons sequenced for validation of results. Twenty ticks, in a total of 428, were found positive: one Ixodes ventalloi for Theileria annulata and four Dermacentor marginatus, one Haemaphysalis punctata, five Ixodes ricinus, five I. ventalloi, and four Rhipicephalus sanguineus sensu lato for A. marginale. According to the reviewed literature, this is the first report of A. marginale and T. annulata detection in I. ventalloi. Furthermore, the amplification of A. marginale DNA in several tick species suggests a broad range for this agent in Portugal that might include other uncommon species as R. sanguineus s.l. This work provides new data towards a better understanding of tick-pathogen associations and also contributes to the surveillance of tick-borne agents in geographic areas with limited information. PMID- 27394442 TI - Gain-switched 311-nm Ti:Sapphire laser might be a potential treatment modality for atopic dermatitis. AB - Phototherapy with 311-nm narrowband-UVB (NBUVB) is an effective adjuvant treatment modality for atopic dermatitis (AD). In this study, we evaluated the therapeutic effect of the newly developed gain-switched 311-nm Ti:Sapphire laser device using a NC/Nga mouse AD model. A total number of 50 mice were used in this study. Atopic dermatitis (AD) was induced in mice by exposure to Dermatophagoides farina. These, NC/Nga mice were then treated with conventional 311-nm NBUVB or the newly developed gain-switched 311-nm Ti:Sapphire laser. The clinical features, dermatitis severity scores, and scratching behavior were assessed. In addition, serologic analyses including inflammatory cytokines and histological analyses were performed. Gain-switched 311-nm Ti:Sapphire laser improved the AD like skin lesions, severity, and symptoms of AD in the NC/Nga mouse model. This new laser also modulated the immune response found in the AD model, including hyper-IgE, upregulated Th2 cytokines, and the Th2-mediated allergic inflammatory reaction. Gain-switched 311-nm Ti:Sapphire laser shows therapeutic promise via an immune-modulation mechanism in an AD mouse model. These data suggest that gain switched 311-nm Ti:Sapphire laser may be useful as a targeted phototherapy modality for AD. PMID- 27394445 TI - Annotated checklist of Georgian oribatid mites. AB - A new updated checklist of Georgian oribatid mites is based on the critical review of existing literature data and new findings. The list includes 534 oribatid species of which 21 species are new for the country recorded from more than 390 locations. For each species information of the global and regional distribution is presented with notes on ecological characteristics. As far as necessary we provide remarks on taxonomic issues to overcome the ambiguities and inconsistencies existing in literature. PMID- 27394444 TI - Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury. AB - Neuropathic pain results from nerve injury and is one of the most refractory disorders. Recently, many studies reported that glial cell-derived neurotrophic factor (GDNF) exhibited potent analgesic effects, but the underlying mechanisms still remain unknown. In addition to the classical GDNF-GFRalpha1-Ret pathway, GDNF can bind to adhesion proteins such as E-cadherin and NCAM via GFRalpha1 in a Ret-independent way. In this study, we aimed to examine whether the adhesion protein nectin-1 and its downstream protein c-Src are involved in neuropathic pain. We found that nectin-1 was expressed in the superficial dorsal horn of the spinal cord and that it was increased after chronic constrictive injury (CCI). Intrathecal administration of nectin-1 siRNA attenuated neuropathic pain induced by CCI via interference of the expression of nectin-1. Furthermore, we found that GDNF can downregulate the phosphorylation level of nectin-1-associated c-Src without changing the expression level of nectin-1. In summary, these data suggest that nectin-1 is involved in neuropathic pain, and that GDNF exerts analgesic effects by directly or indirectly regulating nectin-1/c-Src signaling. These findings may lead to a new target for the treatment of neuropathic pain. PMID- 27394446 TI - A revision of the family Cerococcidae Balachowsky (Hemiptera: Sternorrhyncha, Coccomorpha) with particular reference to species from the Afrotropical, western Palaearctic and western Oriental Regions, with the revival of Antecerococcus Green and description of a new genus and fifteen new species, and with ten new synonomies. AB - The scale insect family Cerococcidae (Hemiptera: Coccomorpha) or false pit scales was last revised during the 1970s and 1980s. At that time, it included three genera, Asterococcus Borchsenius, Cerococcus Comstock and Solenophora Maskell, and a total of 69 species. The present revision concentrates on species known from the western Palaearctic, western Oriental and Afrotropical Regions but includes notes on all known cerococcid species. Within the three geographical areas principally studied here, all known species are described and illustrated based on the adult females, including 13 new species. During this study, a new morphological character was discovered on the venter of the anal lobes that is taxonomically important and which is referred to as the anteroventral sclerotization. It was found that the anteroventral sclerotization was present in most species from the main study areas, but was absent from all species in the Nearctic and from many in the Australasian and Neotropical Regions as well. As the type species of Cerococcus is C. quercus Comstock from the Nearctic, the genus Antecerococcus Green, revived status (type species Cerococcus punctiferus Green) was resurrected to take all species with an anteroventral sclerotization. Resurrection of Antecerococcus means that names of genera previously synonymised with Cerococcus are now junior synonyms of Antecerococcus, e.g., Phenacobryum Cockerell, syn. nov., Amelococcus Marchal, syn. nov., Cercococcus Scott, syn. nov. and Coricoccus Mahdihassan, syn. nov. As a range of other characters also were found to support this division (such as absence of setae along inner margin of each anal lobe and presence of a ventral seta posteriorly on each lobe), the genera in Cerococcidae can be divided into two groups, those with an anteroventral sclerotization (Antecerococcus and probably Solenophora) and those without (Asterococcus and Cerococcus). As part of this revision, it was found necessary to consider the morphological limits of all current genera, including those from outside the western Palaearctic, western Oriental and Afrotropical Regions. This resulted in a new genus, Cerochiton Hodgson & Williams, gen. nov., with three species from the Oriental Region. This genus also falls within the Cerococcus-group of genera. In addition, it was found that, with the inclusion of As. ovoides (Cockerell) from South Africa, Asterococcus was not morphologically monophyletic and so this species has been transferred to Antecerococcus as Antecerococcus ovoides (Cockerell), comb. nov. The following revived combinations are included: Antecerococcus bryoides Maskell and A. stellatus Maskell. In addition, the following Cerococcus species have been transferred to Antecerococcus as comb. nov.: Cerococcus albospicatus Green, C. ankaratrae Mamet, C. asparagi Joubert, C. camarai Neves, C. cistarum Balachowsky, C. cliffortiae Joubert, C. cycliger Goux, C. dumonti Vayssiere, C. fradei Castel-Branco, C. gabonensis Lambdin, C. gallicolus Mamet, C. intermedius Balachowsky, C. laniger Goux, C. longipilosus Archangelskaya, C. madagascariensis Mamet, C. multipororum Lambdin & Kosztarab, C. oranensis Balachowsky, C. ornatus Green, C. passerinae Brain, C. perowskiae Archangelskaya, C. philippiae Lambdin & Kosztarab, C. pileae Mamet, C. pocilliferus Neves, C. polyporus Matesova, C. roseus Green, C. royenae Brain, C. ruber Balachowsky, C. steppicus Balachowsky and C. theydoni Hall. The following have also been transferred to Antecerococcus as comb. nov.: Amelococcus alluaudi Marchal, Cercococcus eremobius Scott, Eriococcus paradoxus indica Maskell, Phenacobryum indigoferae Borchsenius and Pollinia ovoides Cockerell. Two further undescribed species were discovered, one from Mexico and the other from Java, and a number of synonyms were found of names that are now all in Antecerococcus, as follows: Cerococcus camarai Neves is a junior synonym of Cerococcus intermedius Balachowsky, syn. nov.; Cerococcus cycliger Goux is a junior synonym of Cerococcus intermedius Balachowsky, syn. nov.; Phenacobryum indigoferae Borchsenius is a junior synonym of Cerococcus roseus Green, syn. nov.; Cerococcus multipororum Lambdin is a junior synonym of Cerococcus fradei Castel-Branco, syn. nov.; Cercococcus polyporus Matesova is a junior synonym of Cerococcus perowskiae Archangelskaya, syn. nov., and Antecerococcus punctiferus Green is a junior synonym of Cerococcus paradoxus Maskell, syn. nov. In addition, the following new species have been described: Antecerococcus andamanensis Hodgson & Williams, from the Andaman Islands; Antecerococcus capensis Hodgson & Williams, from South Africa; Antecerococcus delottoi Hodgson & Williams, from Kenya; Antecerococcus hilli Hodgson & Williams, from The Seychelles; Antecerococcus insleyae Hodgson & Williams, from South Africa; Antecerococcus kakemegae Hodgson & Williams, from Kenya; Antecerococcus keralae Hodgson & Williams, from southern India; Antecerococcus kurraensis Hodgson & Williams, from Nigeria; Antecerococcus muntingi Hodgson & Williams, from South Africa; Antecerococcus oumeensis Hodgson & Williams, from Ivory Coast; Antecerococcus sparsiporus Hodgson & Williams, from from South Africa; Antecerococcus thesii Hodgson & Williams from South Africa; Antecerococcus yemenicus Hodgson & Williams, from Yemen; Cerochiton bernardi Hodgson & Williams, from Java, and Cerococcus asteris Hodgson & Williams, from Mexico. Thus, at the end of this study, the family Cerococcidae includes five genera and 80 species (Antecerococcus with 55 species (13 of them new), Asterococcus with eight species, Cerochiton with three species (one of them new), Cerococcus with 13 species (1 of them new and including two unplaced species), and Solenophora with one species). Keys are provided for the separation of the five genera and also for the species in each genus based on adult female morphology. Lectotypes have been designated for Cerococcus asparagi Joubert, C camarai Neves, C. cistarum Balachowsky, C. cliffortiae Joubert, C. coffeae Vayssiere, C. cycliger Goux, C. dumonti Vayssiere, C. hibisci Green, C. intermedius Balachowsky, C. laniger Goux, C. pocilliferus Neves, C. royenae Brain and C. ruber Balachowsky, and for Cercococcus eremobius Scott and Solenophora coloradensis Cockerell. In addition, it was found that the lectotype of Eriococcus paradoxus Maskell (now Antecerococcus paradoxus) had been designated based on a specimen of Eriococcus paradoxus indica Maskell (now Antecerococcus indicus). This designation has been revoked and new lectotypes for Eriococcus paradoxus and Eriococcus paradoxus indica have been designated. Following the taxonomic section, the geographic distribution of each genus is briefly discussed. Asterococcus (with the removal of A. ovoides) is now restricted to the Oriental Region; Cerochiton is restricted to the southern part of the Oriental Region; Cerococcus appears to be restricted to Central and North America, while Antecerococcus has a world-wide distribution but is most abundant in the western Palaearctic, western Oriental and Afrotropical Regions. The single species now in Solenophora is only known from New Zealand. Two species, "Cerococcus" indonesiensis Lambdin & Kosztarab and "Cerococcus" michaeli Lambdin do not appear to belong to Cerococcus, but are being left there pending further studies and are referred to here as "unplaced species". PMID- 27394443 TI - Neuroprotective Effect of Osthole on Neuron Synapses in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9. AB - Accumulation of beta-amyloid peptide (Abeta) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). It has been reported that osthole exerts its neuroprotective effect on neuronal synapses, but its exact mechanism is obscure. Recently, microRNAs have been demonstrated to play a crucial role in inducing synaptotoxicity by Abeta, implying that targeting microRNAs could be a therapeutic approach of AD. In the present study, we investigated the neuroprotective effects of osthole on a cell model of AD by transducing APP695 Swedish mutant (APP695swe, APP) into mouse cortical neurons and human SH-SY5Y cells. In this study, the cell counting kit CCK-8, apoptosis assay, immunofluorescence analysis, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction, and Western blot assay were used. We found that osthole could enhance cell viability, prevent cell death, and reverse the reduction of synaptic proteins (synapsin-1, synaptophysin, and postsynaptic density-95) in APP-overexpressed cells, which was attributed to increases in microRNA-9 (miR-9) expression and subsequent decreases in CAMKK2 and p-AMPKalpha expressions. These results demonstrated that osthole plays a neuroprotective activity role in part through upregulating miR-9 in AD. PMID- 27394447 TI - Cladistic analysis of Subfamily Bruchomyiinae (Diptera: Psychodidae). AB - Subfamily Bruchomyiinae is comprised of 60 species and has been referred to as the most primitive within the Psychodidae. The assumed sister-group relationship with Phlebotominae is based on ecological constraints of their environment. A cladistics analysis based on 29 characters and 52 species revealed the distinction of an Old World clade characterized by males with elongate, narrow vasa deferentia, and a New World clade with males having shorter and basally widened vasa deferentia. The Old World clade consists of the genera Nemopalpus Macquart (9 species), and Eutonnoiria Alexander (1 species). The New World clade includes Bruchomyia Alexander (10 species), Boreofairchildia genus nov. (13 species), Laurenceomyia genus nov. (5 species), and Notofairchildia genus nov. (15 species). Parsimony and Bayesian analyses resulted in trees that generally support this generic classification; however, with some species groups less resolved. Diagnostic features for genera are provided. In contrast to the other New World genera, Notofairchildia is paraphyletic with the provisional inclusion of at least the Australasian taxa. PMID- 27394448 TI - Porcelain crabs from Brazil (Crustacea: Decapoda: Anomura: Porcellanidae). AB - Twenty species of porcelain crabs are reported on the basis of material collected from Brazilian coasts. Considering the lack of systematic studies comprehending the Brazilian porcellanids, the present work presents a review of the regional species based on the current taxonomic information. New records, information about variation between specimens and a taxonomic discussion are given for porcellanid crabs from Brazil. PMID- 27394449 TI - Two new species of Xosopsaltria Kirkaldy, 1904, with a key to the species of South African pygmy bladder cicadas (Hemiptera: Cicadidae: Cicadettinae: Tettigomyiini). AB - Two species, Xosopsaltria brachyptera n. sp. and Xosopsaltria vitripennis n. sp., are described as new. Notes on their biology and a key to the South African pygmy bladder cicadas are also provided. PMID- 27394450 TI - Revision of the Dysmorphoptilidae (Hemiptera: Cicadomorpha: Prosboloidea) of the Queensland Triassic-Part 2. AB - The extinct hemipteran family Dysmorphoptilidae was a major component of the Triassic insect fauna of Queensland preserved at the Denmark Hill, Dinmore, Mount Crosby and Gayndah fossil insect sites. A total of 13 species have now been identified, of which eight species in five genera were examined in the first part of this revision. This second part revises the remaining five species in three genera. Eoscartoides Evans, 1956 (= Mesonirvana Evans, 1956, syn. nov.), comprising Eoscartoides bryani Evans, 1956 (= Mesonirvana abrupta Evans, 1956, syn. nov.) (Mount Crosby), Eoscartoides orthocladus (Tillyard, 1922) comb. nov. (Denmark Hill), and Eoscartoides dmitryi sp. nov. (Dinmore), is distinguished by a strongly developed arc-like strigil in the basal costal space, a very short stem of RA, and a deeply forked M1+2. The monotypic Eoscarterella Evans, 1956, with type species Eoscarterella media Evans, 1956 (Mount Crosby), has a strongly lobate tegmen with peculiar surface sculpture and M1+2 simple. Eoscartoides and Eoscarterella differ from most dysmorphoptilids in having more or less lobate tegmina with even margins (without the antero-apical emargination so typical of the family), as well as the early entry of RA1 into the costal margin and the associated extensive and antero-apically positioned RA2. These characters are also shared with two other dysmorphoptilids, the Australian Permian Belmontocarta Evans and an unnamed Triassic species from Kyrgyzstan, and the four thus form a distinct subgroup within the family. On the other hand, the monotypic Trifidella Evans, 1956 (= Alotrifidus Evans, 1956, syn. nov.), with type species Trifidella perfecta Evans, 1956 (= Alotrifidus interruptus Evans, 1956, syn. nov.) (Mount Crosby), is a more typical dysmorphoptilid with a distinct emargination, RA entering the margin much more apically, and RA2 of limited extent. Trifidella is presumably the sister of the Queensland Triassic Dysmorphoptiloides Evans, sharing the basal fusion of M and CuA. PMID- 27394451 TI - A molecular phylogenetic study on South Korean Tettigonia species (Orthoptera: Tettigoniidae) using five genetic loci: The possibility of multiple allopatric speciation. AB - In Korea, members of the genus Tettigonia have been known as two species, T. ussuriana and T. dolichoptera dolichoptera. However, the taxonomic status of the Jeju Island population of T. ussuriana (JJ-TU) is in question, relative to the mainland population (ML-TU), because of their different body sizes and ratios of wing length. To clarify the relatedness of JJ-TU and ML-TU, we examined the genetic variation and phylogenetic relationships within and between T. ussuriana and related species collected in South Korea, using five genetic loci: three mitochondrial genes (cytochrome c oxidase subunit 1 [CO1], cytochrome c oxidase subunit 2 [CO2], NADH dehydrogenase 1 [ND1]) and two nuclear loci (second internal transcribed spacer [ITS2], and tubulin alpha-1 [TA1]). Unexpectedly, the JJ-TU population is explicitly sister to T. d. dolichoptera, with low genetic distance (0.76-1.22% in CO1), indicating no direct connection with the ML-TU population; this finding suggests a recent divergence involving rapid morphological change without gene flow between JJ-TU and mainland T. d. dolichoptera. The separation of these populations from their common ancestor was caused by geographical isolation during last glacial age. This finding indicates that the JJ-TU population should be elevated to the rank of subspecies, at the very least. Furthermore, the ML-TU population was also revealed to have four genetically divided groups (group A-D) from four localized populations, but no significant morphological differences exist among them. The genetic difference (range 3.19-4.10% in CO1) between group A + B and C + D was especially large, suggesting that cryptic speciation has widely occurred within the mainland areas, caused by allopatric isolations resulting from mountain barriers. PMID- 27394452 TI - The transfer of two clades of Malaysian Sphenomorphus Fitzinger (Squamata: Scincidae) into the genus Tytthoscincus Linkem, Diesmos, & Brown and the description of a new Malaysian swamp-dwelling species. AB - Phylogenetic analyses based on the mitochondrial gene ND2 and its flanking tRNAs indicate the diminutive upland and insular species Sphenomorphus bukitensis, S. butleri, S. langkawiensis, S. perhentianensis, and S. temengorensis form a monophyletic group that is phylogenetically embedded within the Southeast Asian genus Tytthoscincus. The analyses also indicate that a new swamp-dwelling skink from the Bukit Panchor State Park, Pulau Pinang, Peninsular Malaysia is the sister species to the swamp-dwelling species S. sibuensis from Pulau Sibu, Johor and Singapore and that these two are also embedded in the genus Tytthoscincus. By transferring the two Peninsular Malaysian clades of Sphenomorphus into the genus Tytthoscincus, the monophyly of the latter is maintained. The new species T. panchorensis sp. nov. can be distinguished from all other species of Tytthoscincus by having a unique combination of morphological and color pattern characteristics. PMID- 27394453 TI - Three new species of oribatid mites of the family Punctoribatidae (Acari, Oribatida) from alpine bogs of New Zealand. AB - Three new species of oribatid mites of the family Punctoribatidae (Acari, Oribatida) are described from alpine bogs of the Central Otago region in the South Island of New Zealand. Macrogena hexasetosa sp. nov. is morphologically most similar to M. brevisensilla Ermilov & Minor, 2015, however, it differs from the latter by larger body size, the presence of six pairs of genital setae, notogastral and ano-adanal setae of medium size, setiform rostral setae, narrower tutorial cusps, the absence of antero-ventral teeth on genua I, II and femora II, and by the absence of striae on the subcapitular mentum. Porallozetes badamdorji sp. nov. differs from the type species-P. dispar (Hammer, 1973)-by larger body length, the presence of interlamellar setae, short and clavate bothridial setae, anterior notogastral margin, notogastral setae of medium size, semi-oval dorsophragmata, and by the position of notogastral porose areas A2 posteriorly to A1. Safrobates gerdi sp. nov. differs from the type species-S. miniporus Mahunka, 1989-by larger body size, the presence of setiform rostral setae, and by notogastral setae of medium length. Porallozetes and Safrobates are recorded in New Zealand for the first time. Generic diagnoses for Macrogena, Porallozetes and Safrobates are given. PMID- 27394454 TI - Three new species and new distributional data for five rare species of Aphelinus (Hymenoptera: Aphelinidae) from China. AB - Eight species of Aphelinus Dalman (Hymenoptera, Aphelinidae) from China are reviewed. Three species, A. pseudonepalensis sp. nov., A. truncaticlavus sp. nov. and A. maculigaster sp. nov. are newly described, four species, A. meghalayanus Hayat, A. huberi Hayat, A. sharpae Hayat, and A. maculatus Yasnosh are reported as new to China, and A. asychis Walker is newly reported from Tibet, China. A key to the Chinese species of Aphelinus based on females is given. PMID- 27394455 TI - Two new species of Tricorythus Eaton 1868 (Ephemeroptera, Tricorythidae) from Zambia. AB - Larvae, subimagoes, imagoes of both sexes and eggs of Tricorythus furcifer sp.n. and T. tener sp.n. are described based on reared material from Zambia. Larvae of both species closely resemble larvae of T. varicauda (Pictet 1843), while genitals of male imagoes are different, being especially unusual in T. furcifer. A new locality for Tricorythus tinctus Kimmins 1956 is recorded in Zambia. PMID- 27394456 TI - Palpada panorama sp. n. (Diptera: Syrphidae), a big-eyed hoverfly from Peru and Suriname. AB - The hoverfly species Palpada panorama sp. n. (Diptera: Syrphidae) is described based on specimens from Peru and Suriname. It belongs to the scutellaris species group and it is most similar to P. erratica (Curran, 1930), from which it differs most notably by the strongly enlarged ommatidia in the upper half of the eye. Additional differences between these two species and an adjustment for the latest identification key for the species of the scutellaris group are given. PMID- 27394457 TI - Redescription of Protanura papillata Cassagnau & Delamare Deboutteville, 1955 (Collembola, Neanuridae, Neanurinae), with new records from Middle East, and with supplemented diagnosis and key to the genus. AB - The poorly known Neanurini genus Protanura is rediagnosed and briefly compared with Lathriopyga. Protanura papillata Cassagnau & Delamare Deboutteville, 1955, known to date only from Lebanon, is redescribed based on the lectotype and new extensive material from Middle East. PMID- 27394459 TI - On the genera Selwynia Borradaile, 1903, and Gandoa Kammerer, 2006,
with descriptions of two new species from Papua New Guinea and French
Polynesia (Crustacea: Decapoda: Brachyura: Aphanodactylidae). AB - The taxonomy of the Indo-West Pacific aphanodactylid crabs Selwynia sibogae (Tesch, 1918) and S. edmondsoni (Rathbun, 1932) is discussed on the basis of the types, and both species are redescribed and figured. Two new species from Papua New Guinea and French Polynesia respectively, are described and compared with congeners. All are symbionts in polychaete tubes. A key to the genus Selwynia is also provided. The poorly known genus Gandoa Kammerer, 2006, is redescribed on the basis of the rediscovered the type species, Voeltzkowia zanzibarensis Lenz, 1905. The lectotype female of Pinnixa brevipes H. Milne Edwards, 1853, is examined and shown to be a senior subjective synonym of G. zanzibarensis. PMID- 27394458 TI - A review of the genus Kanakia Distant, 1892 (Insecta: Hemiptera, Cicadoidea, Cicadidae) from New Caledonia. AB - Among New Caledonian cicada taxa, the endemic genus Kanakia Distant, 1892 appears as the most spectacular one, especially because of the large size of its species (length up to 50 mm for males). Recent new specimen collections helped to clarify the taxonomy of this spectacular genus. According to morphological characteristics, we were able to redefine and to split the present genus into three distinct genera: Kanakia Distant, 1892, Pseudokanakia Delorme gen. nov. and Panialna Delorme gen. nov. These two new genera are monotypic and have been respectively established from revision of Kanakia flavoannulata (Distant 1920) and Kanakia parva Boulard 1991. Also, the type species, Kanakia typica Distant, 1892, appears to be a complex of cryptic species. New acoustic and morphological observations allowed us to redefine K. typica and to describe four new species in this complex: Kanakia paniensis Delorme sp. nov., Kanakia rana Delorme sp. nov., Kanakia salesnii Delorme sp. nov. and Kanakia fuscocosta Delorme sp. nov. Kanakia gigas Boulard 1988 is also briefly discussed and the female is described. An identification key of the Kanakia species and allied genera is also provided. PMID- 27394460 TI - Species of the genus Arthrobrachus Solier, 1849 (Coleoptera: Melyridae)
distributed to the East of the Andes. AB - The species of the genus Arthrobrachus Solier, 1849 distributed in Argentina, Bolivia, Paraguay and Uruguay have been revised. The morphological study of specimens and the review of the type material have resulted in a new combination: Arthrobrachus flavomarginatus (Blanchard, 1843) n. comb. (from Astylus Laporte, 1836), and four new synonymies: Arthrobrachus rufitarsis Philippi & Philippi, 1864 = A. obscuripes Pic, 1927 n. syn.; Arthrobrachus flavomarginatus (Blanchard, 1843) = A. xanthurus (Blanchard, 1843) n. syn. = A. boucardi Pic, 1919 n. syn. = A. lajoyei Pic, 1919 n. syn. Three species described by Steinheil (1874), Arthrobrachus depressus, Arthrobrachus testaceolimbatus and Arthrobrachus testaceus are considered as incertae sedis and Arthrobrachus quadrilineatus Steinheil, 1874 is transferred to Astylus Laporte, 1836 as A. steinheili nomen novum. Four new species of Arthrobrachus have been described: A. antonioi n. sp., A. eloisae n. sp., A. solervicensi n. sp. and A. armandoi n. sp. Distributional data and a key to the species are provided. PMID- 27394461 TI - Chelidoperca stella, a new species of perchlet (Perciformes: Serranidae) from the Andaman Sea, eastern Indian Ocean. AB - A new species of serranid fish, Chelidoperca stella, is described on the basis of five specimens from the Andaman Sea in the eastern Indian Ocean. The species can be readily distinguished from all valid congeners by having fewer pored lateral line scales (34 or 35 vs. 40-45 in the latter) and the pelvic fin white with several small yellow spots (vs. spots absent). The species is also characterized by having relatively high counts of small serrae on the posterior margins of the preopercle (33-43 serrae), interopercle (7-10) and subopercle (18-28), despite the small body size (51.7-61.8 mm SL). Although Chelidoperca stella resembles C. margaritifera in having 2.5 scale rows between lateral line and the sixth dorsal fin spine base, a relatively wider interorbital region, and the interorbital scales not reaching a vertical through the orbit anterior margin, but differs by having the above-mentioned diagnostic characters plus a slightly shorter longest anal-fin soft ray [17.4-18.7 (mean 18.1) % SL vs. 22.6-26.4 (24.4) % SL in C. margaritifera]. PMID- 27394462 TI - Three new species of Acidiostigma Hendel (Diptera: Tephritidae: Trypetinae) and an updated key to species from the eastern Palaearctic and Oriental Regions. AB - Three new species of Acidiostigma Hendel from China are described and illustrated. The new species are A. nigrofasciola Chen and Zhang, sp. nov., A. subpostsignatum Chen and Zhao, sp. nov. and A. tongmaiense Chen, sp. nov. An updated key to the known species of the genus is provided. The male of A. bimaculatum Wang and female of A. postsignatum (Chen) are newly recorded, described and illustrated. The biology and behaviour of A. bimaculatum Wang and A. postsignatum (Chen) are observed in the field and recorded for the first time. PMID- 27394463 TI - Taxonomy, phylogeny, and distribution of Bronchocela rayaensis (Squamata: Agamidae) on the Thai-Malay Peninsula. AB - An integrative taxonomic analysis used to identify a new population of Bronchocela from Phuket Island, Thailand indicates it is conspecific with B. rayaensis from the Langkawi Archipelago of northwestern Peninsular Malaysia. An additional specimen photographed from Khura Buri District, Phang-nga Province is also considered to be B. rayaensis and represents a northern range extension of 295 km from the Langkawi Archipelago. PMID- 27394464 TI - The taxonomic status of Tantilla marcovani Lema 2004 (Squamata: Colubridae). AB - The colubrid snake genus Tantilla currently comprises 62 valid species distributed from the southern United States of America to southern Bolivia in the west, and Uruguay and northern Argentina in the east (Wilson & Mata-Silva 2014, 2015). Of these 62 species, 13 are found in South America (Wilson & Mata-Silva 2014, 2015). The most recently described of these Southamerican species is Tantilla marcovani Lema, 2004. While we were working on a checklist and key to the members of the Tantilla clade (sensu Holm 2008, including the genera Geagras Cope 1876, Scolecophis Fitzinger 1843, Tantilla Baird & Girard 1853, and Tantillita Smith 1941; Wilson & Mata-Silva 2015), it became apparent that the diagnosis of T. marcovani entirely falls to distinguish this nominal taxon from the widespread and extensively variable T. melanocephala Linnaeus 1758. Tantilla melanocephala, as presently envisioned, is the most broadly distributed member of its genus (Wilson & Mena 1980; Savage 2002; Greenbaum et al. 2004), occurring from Panama southward into the major portion of the South American continent, apart from Chile and southern Argentina. PMID- 27394465 TI - A new genus and species of chigger mite (Trombidiformes: Trombiculidae) from Loxodontomys pikumche (Rodentia: Cricetidae) in Chile. AB - The family Trombiculidae is one of the most diverse and cosmopolitan (Walter et al. 2009). In Chile, the family Trombiculidae is represented by six genera associated with reptiles: Eutrombicula Ewing; Microtrombicula Ewing; Paratrombicula Goff & Whitaker; Whartonacarus (Brennan & Jones); Diaguitacarus Stekolnikov & Gonzalez-Acuna and Proschoengastia Vercammen-Grandjean and two genera associated with rodents Chilacarus Webb, Bennett & Loomis and Poliremotus Brennan & Goff (Stekolnikov & Gonzalez-Acuna 2015). PMID- 27394466 TI - Baculentulus kulsarinae sp. nov. from Thailand (Protura: Acerentomata, Acerentomidae). AB - Proturan fauna of Thailand has so far been poorly known, only two contributions being hitherto published. Imadate (1965) recorded 26 species from around the country and Nakamura and Likhitrakarn (2009) reported eight species including three new species from Doi Suthep-Pui National Park, Chiang Mai Province. PMID- 27394467 TI - Synemon ignita sp. nov., a new sun moth species from southern Australia (Lepidoptera, Castniidae). AB - Sun moths (Castniidae) constitute a family of day-flying moths that due to their slim bodies, broad and often richly coloured wings and clubbed antennae closely resemble butterflies. However, despite this superficial similarity, sun moths are not related to butterflies but belong to the diverse cossoid assemblage of lepidopterous families (Edwards et al. 1998). Until recently, Castniidae were assigned to the superfamily Sesioidea (Minet 1991). A molecular study by Mutanen et al. (2010), however, failed to find support for a close relationship of Sesiidae and Castniidae, resulting in the inclusion of both families in a larger concept of Cossoidea (Nieukerken et al. 2011). In contrast, Heikkil et al. (2015) who added considerable morphological data to DNA, recovered Sesioidea as monophyletic, with Sesiidae, Castniidae and Brachodidae as constituent families, yet with low support values. Thus, although the monophyly of Castniidae is well supported, the systematic position of this family is unresolved. PMID- 27394468 TI - New additions to the leafhopper genus Salka Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae) from Hainan and Henan Provinces of China. AB - The leafhopper genus Salka Dworakowska, 1972 belongs to the Typhlocybinae tribe Erythroneurini with Zygina nigricans Matsumura, 1932 as its type species. The known species of this genus are distributed in the Oriental and Palearctic regions. Recently, it was reviewed by Zhang et al. (2009), Ohara (2012) and Song & Li (2012). Seventy-eight species are known, including 36 species from China. In this present work, two new species from China are described and illustrated. All specimens examined are deposited to the collection of the Institute of Entomology, Guizhou University, China (GUGC). PMID- 27394469 TI - A review of New Zealand and southeast Australian echinothurioids (Echinodermata: Echinothurioida)-excluding the subfamily Echinothuriinae-with a description of a new species of Tromikosoma. AB - An examination of a large collection of echinothurioid echinoids (excluding the subfamily Echinothuriinae Thomson) from museum collections in New Zealand and Australia has expanded the known diversity of the group in New Zealand from three species in two genera to seven species in five genera, and revealed a new species in the genus Tromikosoma Mortensen.New records for New Zealand and Australia are reported for Sperosoma obscurum Agassiz and Clark, 1907 and S. nudum Shigei, 1978 and new records for New Zealand are reported for Tromikosoma australe (Koehler, 1922) and Kamptosoma asterias (A. Agassiz, 1881). Tromikosoma rugosum sp. nov., remarkable for its unusual wrinkled appearance and exceedingly thin test, is described from deep water in the northeast of New Zealand. No evidence for the existence of Phormosoma rigidum A. Agassiz, 1881 as a species separate from P. bursarium A. Agassiz, 1881 was found, and synonymy with P. bursarium is proposed.Previous records of these echinoid species were rare, as they live mostly in deep water (>1000 m), and three species were previously known from the type material alone. Tromikosoma rugosum sp. nov. now falls into that category, but new material of the other species greatly expands both the number of known records and their geographical distribution. The majority of these new records are from the New Zealand region, with several additional records from south-east Australia.An updated key to the echinothurioids of New Zealand is provided. PMID- 27394470 TI - The Canacidae of the Arabian Peninsula (Diptera: Brachycera: Carnoidea). AB - A review of the canacid fauna of the Arabian Peninsula is provided. In addition to the usual taxonomic account, a key to all genera and species is also provided. Many figures illustrate some of the main characters that will hopefully be useful for identifying some taxonomically difficult species. PMID- 27394471 TI - Grandidierella bonnieroides Stephensen, 1948 (Amphipoda, Aoridae)-first record of an established population in the Mediterranean Sea. AB - The first record in the Mediterranean Sea of the invasive aorid amphipod crustacean Grandidierella bonnieroides is presented. A widespread circumtropical species, recorded off the Saudi coast of the Arabian Gulf, the Red Sea and the Suez Canal, it may have been introduced into the Mediterranean through the Suez Canal. This tube-builder species of soft bottoms recently established a population in the polluted Haifa Bay, Israel. Further, this is the first Mediterranean record of the genus. PMID- 27394472 TI - Complete mitochondrial genomes of three crickets (Orthoptera: Gryllidae) and comparative analyses within Ensifera mitogenomes. AB - The complete mitochondrial genomes (mitogenomes) of Velarifictorus hemelytrus, Loxoblemmus equestris and Teleogryllus emma are 16123 bp, 16314 bp and 15697 bp, in size, respectively. All three mitogenomes possess the same gene order of the inversion of the gene cluster trnE-trnS(AGN)-trnN compared with the ancestral gene order of Orthoptera. The atypical initiation codon for the cox1 gene in three crickets is TTA. Pronounced A skew and T skew have been found in Grylloidea comparing with Gryllotalpoidea and Tettigonioidea. The T-stretch in the minority strand is interrupted by C to form (T)n(C)2(T)n sequences in five species of Gryllinae (V. hemelytrus, L. equestris, T. emma, T. oceanicus, T. commodus). This T-stretch variant with its neighbouring A-stretch variant (A-stretch is interrupted by G), which were discovered in the A+T-rich regions of all taxa from infraorder Gryllidea, could form a conserved stem-loop structure (including 15 ~ 17 base pairs). This potential stem-loop structure is a favorable candidate that may participate in the replication origin of the minority strand of Gryllidea mitogenome. Phylogenetic analysis indicated that within the Gryllinae, genus Teleogryllus and Velarifictorus are closely related, sister to the genus Loxoblemmus. The relationships among the five superfamilies of Ensifera presented here were ((Grylloidea, Gryllotalpoidea) (Tettigonioidea, (Hagloidea, Rhaphidophoroidea))). PMID- 27394473 TI - Checklist of Aphidiinae (Hymenoptera: Braconidae) and Aphelinus (Hymenoptera: Aphelinidae) species from Belgium with respectively four
and three new records. AB - Aphid parasitoids have good potential for crop protection. However, they have been poorly studied in Belgium, especially in terms of species diversity. Therefore, the aim of this work was to establish the first checklist for the country. To complete the list, aphid parasitoids were sampled in wheat and pea fields near Gembloux (Belgium), in 2013 and 2014. Among the identified species, Aphelinus asychis Walker, Aphelinus daucicola Kurdjumov, Aphelinus fusciscapus (Forster), Aphidius asteris Haliday, Aphidius eadyi Stary, Gonzalez & Hall, Praon barbatum Mackauer, and Trioxys auctus (Haliday) were recorded for the first time in Belgium. Thirty-two Aphidiinae and seven Aphelinus species were included in the checklist. It is hoped this study will stimulate further research, as species diversity is still low compared with neighbouring countries. PMID- 27394474 TI - Elanela Rolston revisited (Heteroptera: Pentatomidae): new distributional records and description of new species. AB - Menidini is highly diverse in the Paleartic and Afrotropical regions. Only two genera, Rio Kirkaldy and Elanela Rolston, are currently known from the Neotropical region. Here we describe five new species of Elanela: E. nigrofemorata sp. nov., E. diamphidiosa sp. nov., E. rafaeli sp. nov., E. fernandesi sp. nov., and E. scutomaculata sp. nov. The generic diagnosis of Elanela is modified to accommodate the new species and a dichotomous key is provided. PMID- 27394475 TI - A new genus and two new species of soldier fly (Diptera: Stratiomyidae: Chiromyzinae) from Australia, one found infesting sugarcane in central Queensland. AB - Metridius nov. gen. and types species M. robertsoni nov. sp. with winged males and apterous females is described from adults and larvae found infesting sugarcane stools from near Mackay, central Queensland. A second new species, M. mcalpinei nov. sp., based only on males from near Sydney, New South Wales is also described. Notes on the biology of both species and an identification key to the genera of the subfamily Chiromyzinae and to the species are also given. PMID- 27394476 TI - Descriptions of little-known and unknown morphs of Periphyllus acerihabitans Zhang (Hemiptera: Aphididae: Chaitophorinae). AB - Periphyllus acerihabitans Zhang, 1982, associated with Acer buergerianum, is known only from the original description from China. Based on the type series and specimens collected in Japan, we re-describe apterous and alate viviparous females of P. acerihabitans and describe dimorph (aestivating nymph) and oviparous female in detail with illustrations. This is the first record of this species from Japan. The differences between P. acerihabitans and a related species P. viridis (Matsumura, 1919) are discussed. Keys to similar species: P. acerihabitans, P. viridis and P. californiensis (Shinji, 1917), associated with A. buergerianum or A. pictum subsp. mono, are provided. PMID- 27394477 TI - Re-description of Cephalobus topali Andrassy, 1970 (Rhabditida, Cephalobidae) from Vietnam, and transfer to Acrobeloides (Cobb, 1924) Thorne, 1937. AB - Recently, specimens of Cephalobus topali, collected from an agricultural area from northern Vietnam, are described, including SEM study. They are characterized by their its 306-347 um long body in females, lateral field with two alae or 3-4 longitudinal incisures, lip region with three pairs of asymmetrical conoid lips, three low and rounded labial probolae separate from the corresponding pair of lips by an incisure, U-shaped primary axils without guard processes, V-shaped secondary axils without guard processes, pharyngeal corpus slightly fusiform and 2.6-3.1 times the isthmus length, spermatheca and postvulval sac poorly developed, female tail conoid (18-24 um, c = 12.7-17.0, c' = 1.8-2.7) with rounded terminus ending in an acute or wart-shaped mucro, phasmid at 29-34% of tail length, and male unknown. SEM pictures reveal that lip region pattern significantly differs from that found in members of Cephalobus and fits that observed in Acrobeloides, so that the species is transferred to this genus. Cephalobus quadrilineatus is provisionally maintained as different from C. topali. PMID- 27394478 TI - An inconspicuous, conspicuous new species of Asian pipesnake, genus Cylindrophis (Reptilia: Squamata: Cylindrophiidae), from the south coast of Jawa Tengah, Java, Indonesia, and an overview of the tangled taxonomic history of C. ruffus (Laurenti, 1768). AB - We describe a new species of Cylindrophis currently known only from Grabag, Purworejo Regency, Jawa Tengah Pro-vince (Central Java), Java, Indonesia. Cylindrophis subocularis sp. nov. can be distinguished from all congeners by the presence of a single, eponymous subocular scale between the 3rd and 4th or 4th and 5th supralabial, preventing contact between the 4th or 5th supralabial and the orbit, and by having the prefrontal in narrow contact with or separated from the orbit. We preface our description with a detailed account of the tangled taxonomic history of the similar and putatively wide-ranging species C. ruffus, which leads us to (1) remove the name Scytale scheuchzeri from the synonymy of C. ruffus, (2) list the taxon C. rufa var. javanica as species inquirenda, and (3) synonymize C. mirzae with C. ruffus. We provide additional evidence to confirm that the type locality of C. ruffus is Java. Cylindrophis subocularis sp. nov. is the second species of Asian pipesnake from Java. PMID- 27394479 TI - A new species of the genus Microgecko Nikolsky, 1907 (Sauria: Gekkonidae) from southern Iran. AB - The dwarf geckos of the recently revived genus Microgecko Nikolsky, 1907 comprise four species, ranging from western Iran to northwestern India. Iran hosts three species of the four recognized species of the genus Microgecko. Here, we describe a new species of this genus based on two and single specimens from southeastern and southern Iran, respectively. Combinations of scalation characters and distinct morphology, coloration and habitat peculiarities in calcareous mountains distinguish Microgecko chabaharensis sp. nov. from its congeners. Detailed information and an updated identification key for the genus Microgecko are also presented. PMID- 27394480 TI - A new large species of Bitis Gray, 1842 (Serpentes: Viperidae) from the Bale Mountains of Ethiopia. AB - A new species of viperine viperid snake is described, Bitis harenna sp. nov. The new species is a member of the subgenus Macrocerastes based on it having three scales separating the nasal and rostral shields, and on the combination of 'divisions' of dorsal scale rows on the upper flanks and 'fusions' of rows on the lower flanks. Bitis harenna sp. nov. is distinguished from other members of the subgenus by its unique colour pattern, posterior parietal flange on the lateral wall of the braincase, and possibly by differences in scalation and head proportions. Only a single museum specimen is known, a female collected from 'Dodola' in Ethiopia probably in the late 1960s and previously identified as a possibly unusually coloured and patterned B. parviocula. A live, presumably male, specimen very closely resembling the holotype of Bitis harenna sp. nov. was photographed on the Harenna escarpment of the Bale Mountains National Park, Ethiopia in 2013, providing secure occurrence data and evidence that the holotype is not a uniquely aberrant specimen. A revised key to the species of Bitis in Ethiopia is presented. Aspects of body scalation are compared among species of the subgenus Macrocerastes and between species of Macrocerastes and Bitis, and several systematic characters are highlighted and clarified. PMID- 27394481 TI - Three new species and one new record of Tullbergiidae (Collembola: Onychiuroidea) from Tierra del Fuego. AB - Three new species, Tullbergia rapoporti sp. nov., Dinaphorura nerudai sp. nov. and Dinaphorura najtae sp. nov., and one new record, Tullbergia meridionalis Cassagnau & Rapoport, 1962 are described based on specimens from Tierra del Fuego. Tullbergia rapoporti sp. nov. is similar to T. crozetensis, but can be distinguished from it by the presence of an empodial appendage and the chaetotaxy of Abd VI. Dinaphorura nerudai sp. nov. is diagnosed by the dorsal pso formula, the seven spiniform processes on Abd VI, an elongate PAO, the absence of vesicle on Ant IV and the dorsal chaetotaxy. Dinaphorura najtae sp. nov. is characterised by the dorsal pso formula, the seven spiniform processes on Abd VI, a triangular PAO, the absence of vesicle on Ant IV and the dorsal chaetotaxy. PMID- 27394483 TI - New species of Loneuroides Garcia Aldrete (Psocodea: 'Psocoptera': Ptiloneuridae) from Colombia, and description of the male L. venezolanus Garcia Aldrete. AB - Six species of Colombian Loneuroides Garcia Aldrete are here described and illustrated; also, the male of L. venezolanus Garcia Aldrete is described, on basis of specimens from Valle del Cauca, Colombia. An updated diagnosis of the genus is presented; two species groups, based on the structure of the hypandrium, are recognized in the genus. PMID- 27394482 TI - The genus Cixius Latreille, 1804 (Hemiptera, Fulgoromorpha, Cixiidae) in Lebanon with the description of two new species. AB - A first list of Cixius fauna of Lebanon is here provided with the description of two new species: one within the subgenus Acanthocixius, Cixius bifidispinus sp. nov. and one within the subgenus Ceratocixius Cixius superremotus sp. nov. The standard morphological description is supplemented by sequence data of the mitochondrial cytochrome c oxidase subunit I (COI) gene fragment. Some notes on their distribution and economic importance are also reported. PMID- 27394484 TI - A review of the baconii species group of the termitophilous genus Orthogonius Macleay (Coleoptera: Carabidae: Orthogoniini). AB - The baconii species group of the termitophilous carabid genus Orthogonius Macleay, 1825, is defined and reviewed. This group is known only from southern Asia and so far recorded by two species: Orthogonius baconii Chaudoir, 1871, from India and O. nepalensis Habu, 1979, from Nepal. Two new species are described and illustrated: O. rogueti n. sp. from southern India and O. ceylanicus n. sp. from Sri Lanka. In addition, a key to all species of this species group is provided. PMID- 27394485 TI - A new species of Spiroberotha Adams 1989 (Neuroptera: Berothidae) and the first record of the genus in Brazil. AB - The genus Spiroberotha Adams, 1989 is classified in Berothidae (Neuroptera) with two described species: S. fernandezi Adams, 1989 from Venezuela and S. sanctarosae Adams, 1989 from Colombia, Costa Rica and Venezuela. Here we describe a new species, S. tocantinensis n. sp., from Palmas, Tocantins, Brazil. This is the first record of the genus in Brazil, extending its geographical distribution. PMID- 27394486 TI - Liliputella, a new genus of microscopic, wingless and blind Scydmaenini of the Bismarck Islands (Coleoptera, Staphylinidae, Scydmaeninae). AB - Liliputella microscopica gen. & sp. nov. is described and placed in the tribe Scydmaenini. This taxon is known from a single male collected on Dyaul Island, the Bismarck Archipelago (Papua New Guinea). With only 0.68 mm of body length, this beetle is one of the smallest within Scydmaenini. Liliputella microscopica is also blind, wingless, strongly flattened and lightly pigmented, suggesting a possible subterraneous habitat. Alternatively, a large and deep ventral cephalic cavity, a unique character not known in any other species of Scydmaeninae, may be a glandular structure indicative of myrmecophily or termitophily. Liliputella shares several interesting characters with genera that also include blind, wingless and presumably subterraneous species, Eudesis and Pseudoeudesis, e.g., humeral denticles, adjacent antennal insertions or strikingly short tarsi. Morphological structures of the new genus are compared with those of other Scydmaenini, and a preliminary identification key to the genera of this tribe is presented. Possible morphological adaptations of Liliputella to miniaturization are also discussed. PMID- 27394487 TI - A new species of Letheobia (Serpentes: Typhlopidae) from central Kenya. AB - A new species of blind snake in the genus Letheobia (L. mbeerensis sp. nov.) is described from the Mbeere area on the extreme lower slopes of southeastern Mt. Kenya. It is an attenuate blind snake, superficially similar to Letheobia lumbriciformis but with 20 midbody scale rows and 670 middorsal scales. It has a total length of 280 mm with the proportionally longest tail in the genus (2.9% of total length), a broad rostral, eyes barely visible and in life it is pink in color. The new species is known from only a single specimen collected at Siakago, in Mbeere-Embu, which lies at an elevation of about 1200m. It is a burrowing species and like many other blind snakes it is likely to be nocturnal and rarely encountered on the soil surface. The new species is incorporated into a key to the scolecophidian snakes of Kenya. PMID- 27394488 TI - Ascidian fauna (Tunicata, Ascidiacea) of subantarctic and temperate regions of Chile. AB - We studied the ascidian fauna from two zones located in subantarctic (Punta Arenas, latitude 53o) and temperate Chile (Coquimbo, latitude 29o). The different oceanographic features of the two zones, with influence of the Humboldt Current in the north and the Cape Horn Current System and freshwater inputs in the south, led to markedly different ascidian faunas. A total of 22 species were recorded, with no shared species across the two areas (11 species each). The new species Polyzoa iosune is described, Lissoclinum perforatum is found for the first time in the Pacific Ocean, and Synoicum georgianum and Polyzoa minor are new to the Chilean fauna. The populations of Ciona in the Coquimbo area (formerly attributed to Ciona intestinalis) correspond to the species Ciona robusta. A total of 35 Cytochrome oxidase (COI) sequences of the standard barcode region have been obtained for 17 of the 22 species reported. PMID- 27394489 TI - Taxonomic revision of the Chinese Limnonectes (Anura, Dicroglossidae) with the description of a new species from China and Myanmar. AB - Phylogenetic reconstructions derived from DNA sequence data play a central role in documenting the number of species in a complex. Such analyses are pointing to the existence of many cryptic species, especially in poorly understood groups such as the genus Limnonectes, and the L. kuhlii species complex in particular. To understand the Limnonectes frogs of China, we reconstruct the major matrilineal genealogy of Limnonectes from China and Southeast Asia based on 12S rRNA, tRNAVal and 16S rRNA gene sequences. Based on new data we recognize five species of Limnonectes in China including L. bannaensis, L. fujianensis, L. fragilis, L. taylori (new record), and a new species from southern China and Myanmar. Phylogenetically, the new species is more closely related to the clade comprising L. taylori, L. megastomias, L. isanensis, L. nguyenorum, and L. jarujini from Thailand than to other Chinese species. This study supports previous findings of sympatric members of a species complex that are not each other's closest relatives. PMID- 27394490 TI - Two new species of Centris (Aphemisia) Ayala, 2002 from Colombia with a synopsis of the subgenus for the country (Hymenoptera: Apidae: Centridini). AB - A synopsis of the species of Centris subgenus Aphemisia Ayala in Colombia is presented. A total of six species were recognized: C. lilacina Cockerell, C. mocsaryi Friese, C. plumipes Smith and C. quadrimaculata Packard, including C. celadonia n. sp. and C. vallecaucensis n. sp., two new species described from the Departments of Huila and Valle del Cauca, respectively. Diagnoses, descriptions, information on geographical distribution and an identification key to all species are provided. The previously unknown male of C. plumipes is described for the first time. PMID- 27394491 TI - The genus Ctenolepisma (Zygentoma: Lepismatidae) in Western Iran, with description of three new species. AB - Several samples belonging to the genus Ctenolepisma Escherich, 1905 collected in western Iran allow us to describe three new species: Ctenolepisma iranicum n. sp., C. sagartianum n. sp. and C. kermanshanum n. sp. Ctenolepisma iranicum n. sp. belongs to the nominate subgenus Ctenolepisma sensu stricto and is closely related to C. ciliatum and C. armeniacum. The other two new species belong to the subgenus Sceletolepisma. They are compared mainly with Asian species belonging to this subgenus, which is reported for the first time in Iran. Moreover, Ctenolepisma sagartianum n. sp. and C. kermanshanum n. sp. show a chaetotaxy that includes them in the species group "villosa", being characterized by bearing a median comb on urosternites II-VI. Additionally, Ctenolepisma armeniacum is reported for the first time in Iran and the male of this species is described. The total number of species of Ctenolepisma known for Iran is seven, although the occurrence of C. mauritanicum has not been confirmed. An identification key for these species is presented. PMID- 27394492 TI - On the identity of Flirtea (Arachnida, Opiliones, Cosmetidae). AB - Flirtea C.L. Koch, 1839, is one of the oldest genera described in Cosmetidae, currently including 30 species mostly from the Andes. Its type species, Cosmetus pictus Perty, 1833, from Brazil, the type material of which is long lost, has since long been misidentified in the literature due to a redescription based on another unrelated species, while the true F. picta was widely known as Flirtea phalerata C.L. Koch, 1840. This unrelated species is here described as Cynorta pictoides sp. nov. Flirtea picta is here redescribed based on abundant material collected in the Brazilian Atlantic Forest biome from Bahia state, and a neotype is designated for its type species. Here, we propose a particular pattern of a white mask blot on the dorsal scutum be called "scaramuccia", and variation in this pattern is described. Genital morphology of Flirtea picta is described for the first time. Flirtea is rediagnosed and most species currently assigned to Flirtea are suggested to belong to other genera. Cynorta valida Roewer, 1928 and Paecilaema batman Pinto-da-Rocha & Yamaguti, 2013 are newly transferred to Flirtea, yielding the new combinations Flirtea valida and Flirtea batman. PMID- 27394493 TI - New data on the Tanaidacea (Crustacea: Peracarida) from the Canary Islands, with a description of a new species of Apseudopsis. AB - Benthic samples from two harbours at El Hierro and Tenerife (Canary Islands) yielded three species of Tanaidacea. Tanais dulongii and Leptochelia savignyi are recorded for the first time in Tenerife and El Hierro, respectively. A new species of Apseudomorpha, Apseudopsis rogi, was collected in both harbours and can be differentiated from other species of the genus by the male having a cheliped merus with a distinctive, cylindrical dorso-proximal spur. This is the first species of Apseudopsis described for the Macaronesian region. A key to the Atlantic and Mediterranean species of Apseudopsis is provided. PMID- 27394494 TI - Review of the little-known western Nearctic fly genus Philetus Melander (Diptera: Empididae), with a discussion of its phylogenetic assignment. AB - The western North American empidid genus Philetus Melander is reviewed, including redescription of the two included species, P. memorandus Melander and P. schizophorus Melander. A lectotype is designated for P. schizophorus. The distributions of both species are mapped and the male terminalia are illustrated. The female of P. schizophorus is discovered for the first time through comparison of COI mitochondrial DNA barcode sequences. The phylogenetic assignment of Philetus within the Empididae is discussed based on a reinterpretation of male terminalia homologies. PMID- 27394495 TI - First records of Enchytraeidae (Annelida, Clitellata) from the Three Parallel Rivers region. AB - The Three Parallel Rivers region is not only an important World Natural Heritage area but also one of the hotspots of world biodiversity with many endemic organisms. However, little is known about the soil fauna of this region, and nothing about enchytraeids. Here we describe two species from the Laojun Mountain, one of the eight eminent mountain chains in this region, Chamaedrilus cf. ozensis Torii, 2015 and Mesenchytraeus laojunensis sp. nov. The latter belongs to a group of Mesenchytraeus species characterized by spermathecae with one ampullar diverticulum and a communication with the oesophagus, and is thus far the southernmost member of this genus in China. It has two exceptional traits within Mesenchytraeus: a large sperm funnel (more than 2000 um in length) and a subterminal attachment of the vas deferens to the atrium. In addition, it is distinguished from the other congeners within this group by coelomocytes with distinct refractile vesicles, five pairs of preclitellar nephridia, and the presence of abundant and flame-shaped sperm bundles in sperm sacs, which extend backwards into XVII-XXII. PMID- 27394496 TI - A revised classification of the Icteridae (Aves) based on DNA sequence data. AB - The higher-level classification of the New World blackbirds (Icteridae; Aves) has remained relatively stable for nearly a half-century, with most currently used classifications (e.g. Sibley & Monroe 1990; Jaramillo & Burke 1999; Fraga 2011; Remsen et al. 2015) following Blake's (1968) delimitation and sequence of genera in the Peters Check-list of Birds of the World series. Early molecular studies (e.g., Lanyon 1992, 1994; Johnson & Lanyon 1999; Price & Lanyon 2002; Cadena et al. 2004) produced only minor modifications. PMID- 27394497 TI - On the status of three nominal species in the synonymy of Dendrelaphis calligaster (Gunther, 1867) (Serpentes: Colubridae). AB - The taxonomic status of three nominal species in the synonymy of the wide ranging Australo-Papuan snake Dendrelaphis calligaster (Gunther, 1867) was investigated. Dendrophis meeki Boulenger, 1895 was shown to represent an insular population of D. gastrostictus instead of D. calligaster and is therefore transferred to the synonymy of the former. A description is given of the syntypes of D. meeki. Dendrelaphis calligaster distinguendus Meise & Hennig, 1932 was found to be fairly distinct from other populations of D. calligaster. However, it is not diagnosable and may not represent an independently evolving lineage. Therefore, its placement in the synonymy of D. calligaster is maintained. A neotype (ZMB 24024) is designated and described because the original types were destroyed during World War II. Finally, Dendrophis salomonis Gunther, 1872 was demonstrated to be indistinct from the D. calligaster metapopulation. It too is maintained in the synonymy of D. calligaster. A description of the syntypes is provided. PMID- 27394498 TI - Revision of Thisiomorphus Pic (Coleoptera: Mycteridae: Eurypinae) with descriptions of eleven new species from Central and South America
and a key to genera of Neotropical Eurypinae. AB - The Neotropical eurypine genus Thisiomorphus is revised, based on external structural features of adults. Twelve species are recognized, including the following eleven new species (type areas in parentheses): T. festivus (Panama, Colon Prov.), T. osaensis (Costa Rica, Puntarenas Prov.), T. davidsoni (Brazil, Chapada), T. inaequalis (Ecuador, Napo Prov.), T. caeruleus (Panama, Panama Prov.), T. brasiliensis (Brazil, Amazonas), T. solisi (Costa Rica, Guanacaste Prov.), T. andrewsi (Panama, Chiriqui Prov.), T. bolivianus (Bolivia, Santa Cruz Dept.), T. curticornis (Ecuador, Sucumbios Prov.), and T. convergens (Brazil, Para). A key to the 13 described eurypine genera of Central and South American is provided, along with a key to species of Thisiomorphus. The keys are supplemented with images of habitus and selected structural features, and maps of known distributions are provided. PMID- 27394499 TI - Elfin butterflies of the genus Rhamma Johnson (Lepidoptera: Lycaenidae: Theclinae): A review of the Colombian species. AB - The Colombian species of the genus Rhamma Johnson, 1992 are revised. Male and female phenotypes of all species are associated and diagnosed, and data on their distributions are given along with a discussion of the geographic variability of the species. Thirteen taxa are considered valid at the species level. The following taxonomic changes are proposed: Rhamma andradei (Le Crom & Johnson), stat. nov, comb. nov.; previously considered a nomen dubium in Penaincisalia Johnson, the taxon is considered a valid species of Rhamma. The placement of Rhamma anosma (Draudt), comb. nov., described as Thecla, is confirmed as belonging to Rhamma. A lectotype is designated for Thecla mishma Hewitson, 1878. Adults, male and female genitalia, and distribution maps are depicted for all species, along with an identification key based on adults. PMID- 27394500 TI - A revision of the Old World species of Leptopsilopa Cresson (Insecta: Diptera: Ephydridae). AB - Diagnoses and illustrations of three Leptopsilopa species known in the Old World: L. africana Cresson, L. mutabilis Cresson and L. pollinosa (Kertesz) are provided. Three new synonyms are proposed: L. aurata (Canzoneri and Meneghini) and L. tibialis (Canzoneri and Meneghini) = L. africana; Psilopa confeteae Canzoneri and Munari = L. pollinosa. Three other species are removed from Leptopsilopa and combined with Athyroglossa, as A. leonensis (Canzoneri and Rampini), new combination, A. mianii (Canzoneri) new combination and A. rossii (Canzoneri and Raffone), new combination. PMID- 27394501 TI - Novel evolutionary lineages in Labeobarbus (Cypriniformes; Cyprinidae) based on phylogenetic analyses of mtDNA sequences. AB - Phylogenetic relationships within Labeobarbus, the large-sized hexaploid cyprinids, were examined using cytochrome b gene sequences from a broad range of geographic localities and multiple taxa. Maximum likelihood and Bayesian methods revealed novel lineages from previously unsampled drainages in central (Congo River), eastern (Genale River) and southeastern (Revue and Mussapa Grande rivers) Africa. Relationships of some species of Varicorhinus in Africa (excluding 'V.' maroccanus) render Labeobarbus as paraphyletic. 'Varicorhinus' beso, 'V.' jubae, 'V.' mariae, 'V.' nelspruitensis, and 'V.' steindachneri are transferred to Labeobarbus. Bayesian estimation of time to most recent common ancestor suggested that Labeobarbus originated in the Late Miocene while lineage diversification began during the Late Miocene-Early Pliocene and continued to the late Pleistocene. The relationships presented herein provide phylogenetic resolution within Labeobarbus and advances our knowledge of genetic diversity within the lineage as well as provides some interesting insight into the hydrographic and geologic history of Africa. PMID- 27394502 TI - Multilocus phylogeny of the Asian Lance-headed pitvipers (Squamata, Viperidae, Protobothrops). AB - Despite the public health significance and potential applications to medical research, the evolutionary history of the Asian Lance-headed pitvipers (genus Protobothrops) remains inadequately studied. Previous research generally focused on a few selected species with no comprehensive molecular study of Protobothrops. Here, we conduct the first study to infer the phylogenetic relationships of all currently recognized species in this genus based on four mitochondrial DNA fragments and four nuclear genes. Bayesian Inference and Maximum Likelihood analyses show that within Protobothrops there are four strongly supported clades forming distinct subgroups. The first subgroup, which is sister to the other three, consists of three species, P. himalayanus, P. kaulbacki, and P. sieversorum. The second subgroup contains only P. mangshanensis. The final two subgroups, which are sister groups, include the other four and six Protobothrops species. Although our findings provide additional information on the phylogenetic relationships of the genus Protobothrops, the placement of P. dabieshanensis and P. elegans remains problematic. In addition, our molecular results indicate that P. trungkhanhensis, currently considered endemic to Vietnam, should be added to the species known from China. Our ancestral area estimation indicated that Protobothrops likely originated in southwestern China. This study improves our understanding of the evolutionary relationships among species of Asian Lance headed pitvipers, providing a greater framework for future studies. PMID- 27394503 TI - Spinacopia dietkeyseri, a new species of Marine Ostracoda (Sarsiellidae: Myodocopina) from the Southern ocean. AB - Spinacopia dietkeyseri, a new species of the family Sarsiellidae is described from the Southern Ocean (61 degrees 48.70' S-47 degrees 28.04' W to 61 degrees 48.57' S-47 degrees 28.19 W) from the depth of 1993-1999 m. It very close to S. mastix Kornicker, 1975, but differs in the ornamentation on the surface of the carapace and in the number of setae on the maxilla, 5th, 6th and 7th limbs. PMID- 27394504 TI - Two new species of diminutive leaf-litter skinks (Squamata: Scincidae: Tytthoscincus) from Gunung Penrissen, Sarawak, Malaysia (northern Borneo). AB - We describe two new species of skinks from Gunung Penrissen, Sarawak, Malaysia, in northern Borneo, Tytthoscincus batupanggah sp. nov. and T. leproauricularis sp. nov. Morphological and molecular analyses both corroborate the two new species as unique compared to all other Tytthoscincus and additional Sphenomorphus that are candidates for taxonomic placement in the genus Tytthoscincus. Despite their phenotypic similarity and sympatric distribution, a molecular analysis shows that the new species are not sister taxa and exhibit a deep genetic divergence between each of their respective sister taxa. We discuss how historical climatic and geographic processes may have led to the co distribution of two relatively distantly related phenotypically similar species. In light of these discoveries, we also emphasize the importance of conserving primary montane tropical rainforest for maintaining species diversity. PMID- 27394505 TI - Latheticomyia Wheeler (Diptera: Pseudopomyzidae) from Peru: new species, description of the male of L. longiterebra Hennig and a key to species. AB - Latheticomyia Wheeler is a small New World genus, with five described species. Here two species from Peru, Latheticomyia peruana sp. nov. and Latheticomyia xantha sp. nov. are described and illustrated. The male of L. longiterebra Hennig is described and illustrated for the first time. Additionally, a key to species is provided. PMID- 27394506 TI - Revision of the Neotropical genus Coroichlorops Paganelli 2002 (Diptera: Chloropidae). AB - Coroichlorops is a monotypic genus of Chloropini known to occur only in South America. The type species, C. yungas (Sabrosky & Paganelli), is formally known only from the holotype, collected in Bolivia. The male genitalia of the genus has peculiar prolonged, forceps-like surstyli. Two additional species of the genus, C. plaumanni sp. nov. and C. antennatus sp. nov., are formally described and illustrated here, and a key to the species of the genus is provided. The atypical flat arista of C. antennatus sp. nov. is also found in the Mepachymerini genus Sagareocerus and its implications are discussed. PMID- 27394508 TI - Review of the genus Arhaphe (Hemiptera: Heteroptera: Largidae) with descriptions of nine new species from Central America. AB - Nine new species of the genus Arhaphe Herrich-Schaeffer, 1850 are described: A. ferruginea sp. nov. from Mexico (Guerrero), A. flavoantennata sp. nov. from Costa Rica (Guanacaste Province), Honduras (Intibuca Department) and Nicaragua (Granada Province), A. hirsuta sp. nov. from Mexico (Oaxaca), A. kmenti sp. nov. from Mexico (Guanajuato, Michoacan), A. longula sp. nov. from Mexico (Guerrero), A. magna sp. nov. from Mexico (Colima), A. myrmicoides sp. nov. from Mexico (Guerrero, Nayarit), A. oaxacana sp. nov. from Mexico (Oaxaca), and A. pilifera sp. nov. from Mexico (Nayarit). The fifth instar larvae of A. arguta (Bliven, 1956), A. carolina Herrich-Schaeffer, 1850, A. cicindeloides Walker, 1873, A. flavoantennata sp. nov., A. mexicana Halstead, 1972, and A. morelensis Brailovsky & Marquez, 1974 are described. Additional state faunistic records of the already described species are provided: A. arguta (Bliven, 1956) (Mexico: Guanajuato, Sonora), A. capitata Halstead, 1972 (Costa Rica; Mexico: Chiapas, Estado de Mexico, Guerrero, Michoacan, Oaxaca, Puebla), A. carolina Herrich-Schaeffer, 1850 (Mexico: Guanajuato, Tamaulipas), A. cicindeloides Walker, 1873 (Mexico: Hidalgo, Queretaro), A. deviatica Brailovsky, 1981 (Nicaragua), A. furcata Brailovsky, 1981 (Mexico: Michoacan), A. halsteadi Brailovsky, 1981 (Mexico: Oaxaca), A. mimetica Barber, 1911 (Mexico: Chihuahua), A. morelensis Brailovsky & Marquez, 1974 (Mexico: Estado de Mexico, Guerrero, Puebla), and A. rustica Brailovsky, 1981 (Mexico: Morelos, Oaxaca). PMID- 27394507 TI - The oldest accurate record of Scenopinidae in the Lowermost Eocene amber of France (Diptera: Brachycera). AB - Eocenotrichia magnifica gen. et sp. nov. (Diptera: Scenopinidae: Metatrichini) is described and illustrated from the Lowermost Eocene amber of Oise (France) and represents the oldest definitive window fly fossil. The present discovery in the Earliest Eocene supports the Late Cretaceous-Paleocene age currently proposed for the emergence of Metatrichini. PMID- 27394509 TI - Reappraisal of species attributed to Halicarcinus White, 1846 (Crustacea: Decapoda: Brachyura: Hymenosomatidae) with diagnosis of four new genera and one new species from New Ireland, Papua New Guinea. AB - Species of Hymenosomatidae previously treated as species or junior synonyms of species of Halicarcinus White, 1846 are assigned to this and other genera. Halicarcinus is restricted to seven valid species; Rhynchoplax Stimpson, 1858, since 1980 synonymised with Halicarcinus, is now recognised with four species; four species are added to Micas Ng & Richer de Forges, 1996 (making five in total); and four new genera are erected: Culexisoma n. gen. (two species, one newly described), Lucascinus n. gen. (three species), Nasutoplax n. gen. (one species) and Stimpsoplax n. gen. (three species). The genera are distinguished primarily on features of the gonopod 1, interaction of the pleon with the thoracic sternal pleonal cavity, maxilliped 3, male cheliped, propodus-dactylus articulation of the ambulatory pereopods, and degree of fusion of the pleomeres. Species of Halicarcinus s.s. share a short trilobed rostrum, strongly curved gonopod 1 and free pleomeres. Some members of other genera may have a similar rostrum but typically have a long median projection with or without lateral angles or spines variously developed at the anterior margin of a supraocular eave. A lectotype of Hymenicus cookii Filhol, 1885 (now Halicarcinus cookii) is designated. A lectotype of Hymenosoma leachii Guerin, 1832, in Guerin-Meneville 1829-1837 (synonym of Halicarcinus planatus Fabricius, 1775) is selected in the interests of nomenclatural stability. Halicarcinus quoyi (H. Milne Edwards, 1853) is recognised as a senior synonym of the more widely used H. innominatus Richardson, 1949, which is itself a nomen nudum because it was erected without type designation. We also recognise Hymenicus marmoratus Chilton, 1882, as a junior synonym of Halicarcinus varius (Dana, 1851). Species of Rhynchoplax share a curved gonopod 1, falcate dactyli on pereopods 2-5 and fused pleomeres 3-4 in males and 3-5 in females. Species of Micas have a twisted gonopod 1 with the apex bent and only one or two subapical teeth on the dactylus of ambulatory legs. Culexisoma n. gen. is established for Halicarcinus ginowan Naruse & Komai, 2009, and a second species, Culexisoma niugini n. sp., from Papua New Guinea as type species. The genus is unique among these genera in having the male pleon not tightly engaging with the thoracic sternum, maxillipeds 3 not fully covering the buccal cavern and in having a strongly sexually dimorphic rostrum. Species of Lucascinus n. gen. share a male cheliped with 'nut-cracker'-like fingers and free pleomeres in both male and female. Nasutoplax n. gen. differs from others in the erect lateral profile of the rostrum and in gonopod 1 with an unusual subterminal spinulose projection on its posterior face. Stimpsoplax n. gen. has a gonopod 1 with a swollen base and a narrow strongly twisted distal part, tapering distally to a curved apex. Each genus is diagnosed, all species are tabulated, some discussed in more detail, and generic diagnostic characters are illustrated. PMID- 27394510 TI - Resurrection of Rhynchoplax Stimpson, 1858, with the description of two new species from Japan and Australia (Crustacea: Decapoda: Brachyura: Hymenosomatidae). AB - Rhynchoplax Stimpson, 1858, is resurrected from synonymy with Halicarcinus White, 1846. Rhynchoplax hondai Takeda & Miyake, 1971, a species based on an immature female, is rediagnosed and two new species, R. magnetica n. sp. from northeastern Australia and R. minutula n. sp. from the Ryukyu Islands, Japan, are described. They differ from R. hondai in the shape of the rostrum, form of the subhepatic region and the armature of the pereopodal meri. All differ from the type species R. messor Stimpson, 1858, in having a longer and simple rostrum without supraocular pseudorostral spines and the absence of a postocular spine. PMID- 27394511 TI - A new species of gecko from arid inland regions of eastern Australia (Diplodactylus; Diplodactylidae). AB - We describe a new species of small terrestrial gecko in the genus Diplodactylus from inland regions of western Queensland and New South Wales, Australia. Diplodactylus ameyi sp. nov. can be distinguished from its congeners in the Diplodactylus conspicillatus species-group by its relatively large size, bulbous tail which lacks an acute attenuated extension at tip, small first labial scale and comparatively robust head morphology (which includes a broadly rounded snout and no well-defined canthus rostralis). Related populations from eastern and central Queensland currently referred to D. platyurus include further deeply divergent lineages but additional material is required to resolve systematic boundaries in this region. PMID- 27394512 TI - Are Phenacoccus solani Ferris and P. defectus Ferris (Hemiptera: Pseudococcidae) distinct species? AB - Among the Nearctic species of Phenacoccus (Hemiptera: Pseudococcidae), Phenacoccus solani Ferris and P. defectus Ferris are morphologically similar and it can be difficult to separate them on the basis of microscopic morphological characters of the adult female alone. In order to resolve their identity, a canonical variates morphological analysis of 199 specimens from different geographical origins and host plants and a molecular analysis of the COI and 28S genes were performed. The morphological analysis supported synonymy of the two species, as although the type specimens of the "species" are widely separated from each other in the canonical variates plot, they are all part of a continuous range of variation. The molecular analysis showed that P. solani and P. defectus are grouped in the same clade. On the basis of the morphological and molecular analyses, P. defectus is synonymized under the senior name P. solani, syn. n. PMID- 27394513 TI - Paracoccus leucadendri Mazzeo & Franco in Mazzeo, Franco & Russo, 2009, a junior synonym of Paracoccus hakeae (Williams, 1985) comb. nov.
(Coccomorpha: Pseudococcidae). AB - Two mealybug species (Hemiptera: Coccomorpha: Pseudococcidae) feeding on Proteaceae in U.S.A. (California), Portugal and Australia were studied: Paracoccus leucadendri Mazzeo & Franco in Mazzeo, Franco & Russo, 2009, described from Portugal, and Phenacoccus hakeae Williams, 1985, described from Australia. A comparative morphological analysis was made of relevant paratypes and additional specimens from Australia, California and Portugal, and the variability of the morphological characters in the populations in each country was documented. Molecular analysis of the COI gene of specimens from Australia and California showed them to be identical, and comparative morphological analysis among specimens from Australia, California and Portugal revealed no differences either; therefore Paracoccus leucadendri is placed as a junior synonym of Phenacoccus hakeae. A comparison of the COI sequences with those of species of Paracoccus, Phenacoccus and other mealybug genera revealed that Phenacoccus hakeae does not belong in Phenacoccus. Even though its COI shows no close match to any other species its morphology fits within the generic concept of Paracoccus, and we transfer it to that genus under the new combination Paracoccus hakeae (Williams, 1985) as a holding option until a comprehensive phylogenetic analysis of the group is carried out. PMID- 27394514 TI - A new species of Moenkhausia Eigenmann, 1903 (Characiformes, Characidae) from the rio Amazonas basin, Brazil. AB - Moenkhausia abyss is herein described from the rio Amazonas basin lowlands. The new species can be distinguished from the congeners by presenting the combination of the following characters: a dark blotch located on the upper caudal-fin lobe and the lower lobe hyaline, 25-29 branched anal-fin rays, humeral spot rectangular, vertically oriented, extending horizontally through two or two and a half scales and located over the third to the fifth lateral line scales, five longitudinal scale rows above the lateral line, predorsal scales arranged in a single not interrupted median row and 30-34 perforated lateral line scales. Brief comments on Moenkhausia megalops are provided. PMID- 27394515 TI - Ufudia, a replacement name for Pelonia Junker & Boomker, 2002 (Pentastomida: Sebekidae) from South African terrapins. AB - In order to accommodate a new species of pentastomid parasite, Pelonia africana Junker & Boomker, 2002 (Sebekidae), Junker & Boomker (2002) described the new genus Pelonia. This genus name is, however, preoccupied by Pelonia Grube, 1859 (Acari). Grube (1859) did not designate a type species, but Oudemans (1900: 141) recorded Pelonia as a possible synonym of Cepheus Koch, 1835 and listed P. foliosa as its type species, allegedly designated by Grube. Subias et al. (2012), accepted the synonymy of Pelonia with Cepheus Koch, 1835 (Acari: Compactozetidae). Norton & Ermilov (2014) provided a brief summary of the nomenclatural history of the mite genus Pelonia and proposed P. foliosa as being the nymph of Cepheus cepheiformis (Nicolet, 1855). PMID- 27394516 TI - A new Polia Ochsenheimer, 1816 species from China (Lepidoptera, Noctuidae, Hadenini). AB - The genus Polia Ochsenheimer, 1816 includes 26 species in the Palaearctic region, with the familiar European species being properly classified (Hacker et al., 2002), while most species from the more diverse Himalayan-region still require a comprehensive revision. Most recently, a new Polia species from China was described by Saldaitis et al. (2013). The sino-tibetian species Polia costirufa (Draudt, 1950) is one of the most interesting members of the complex as it is separable from its relatives at least on the subgeneric level. Certain elements of its forewing pattern resemble those of the genus Heliophobus Boisduval, but P. costirufa is much larger with more elongate forewings. While the P. costirufa male genital capsule shows typical Polia conservative features, the broad, sack like vesica and the huge terminal cornutus are unique in the male and the large, elliptical and strongly sclerotised appendix bursae are unique female characters. The collective of the mentioned external and genital characters are suggesting the justifiable separation of P. costirufa from any other relatives, certainly on subgeneric level, but this would be better to integrate into a study incorporate the complete overview of the Polia-complex in the Himalayan region. P. costirufa male and female genitalia are described here for the first time but further study integrating this species into a complete overview of the Polia complex in the Himalayan region is recommended. PMID- 27394517 TI - Two new species of the genus Eumenes Latreille, 1802 (Hymenoptera: Vespidae, Eumeninae) from Vietnam. AB - Seven species of the genus Eumenes Latreille, 1802, were recorded from Vietnam (Nguyen 2015), including two long-petiolate species (metasomal tergum 1 equal or more than 4 * as long as its maximum width): E. quadratus quadratus Smith and E. multipictus de Saussure, and five species with shorter petioles (metasomal tergum 1 less than 2.5 * as long as its maximum width): E. inconspicuus Smith, E. atrophicus (Fabricius), E. labiatus sinicus Giordani Soika, E. gibbosus Nguyen and E. rubronotatus Perez. Two other long-petiolate species were were described from the Papuan region (Nugroho et al. 2010): E. batantanensis Nugroho and E. truncatus Nugroho. Two new species of the genus Eumenes with long-petiolate metasomal segment 1 are described from Vietnam. A key to all species occurring in Vietnam is also provided. PMID- 27394518 TI - A new species of Neoperla (Plecoptera: Perlidae) from Zhejiang Province of China. AB - The stonefly genus Neoperla Needham (1905) is primarily distributed in eastern North America, Tropical and Temperate Asia and central Africa, with at least 297 species known (Illies 1966, Zwick 1973, Stark & Gaufin 1976, DeWalt et al. 2016). Contributions to Chinese species of Neoperla were made by Chu (1929), Wu & Claassen (1934), Wu (1935, 1938, 1948, 1962, 1973), Yang & Yang (1992, 1995, 1998), Du (1999, 2000a, 2000b), Du et al. (1999, 2001), Du & Sivec (2004, 2005), Du & Wang (2005, 2007), Sivec & Zwick (1987), Li & Wang (2011), Li et al. (2011a, 2011b, 2012a, 2012b, 2013a, 2013b, 2014a, 2014b), Qin et al. (2013), Wang et al. (2013a, 2013b), Li & Zhang (2014), Kong et al. (2014), Wang et al. (2014), Chen & Du (2015). Herein, a new species of this genus is described from Taizhou, Zhejiang Province, of eastern coastal China. PMID- 27394519 TI - A new species of Synchroa Newman from China (Coleoptera: Synchroidae). AB - The family Synchroidae Lacordaire, 1859 is a small group of beetles with an elongate, tapered, and slightly flattened body and brownish to black coloration. Members exhibit morphological similarity to some genera of Melandryidae, but can be distinguished based on larval morphology and the unmodified apical maxillary palpomeres. They are widely distributed throughout the Oriental, Palaearctic and Nearctic regions and possess the highest species diversity in Eastern Asia (Nikitsky 1999; Hsiao 2015). Synchroa bark beetles had been viewed as members of the Melandryidae for a long time, but were treated as an independent family in Boving & Craighead (1931). Crowson (1966) followed Boving & Craighead's treatment and suggested close relatives among the members of Zopheridae and Stenotrachelidae based on both larval and adult characters. Currently, only 8 species distributed amongst three genera have been described in this family: Mallodrya Horn, 1888 is a monotypical genus from North America; Synchroa Newman, 1838, the nominal genus and the largest genus widely distributed in North America, east Palearctic region and the Oriental region, including 5 species; Synchroina Fairmaire, 1898 is from the Oriental region and includes two species. (Nikitsky 1999; Hsiao 2015).Recently, the first author had the opportunity to examine the collection of the Museum of Biology, Sun Yat-Sen University, Guangzhou, China (SYSBM) discovering one remarkable species of Synchroa with dark coloration and a narrow prothorax, which are very different from previously described species of this genus. After careful examination and comparisons to other described species it is described here as new. In addition, an updated key to the world species of Synchroa is provided. PMID- 27394520 TI - Revision of the dwarf cannibal snails (Nata s.l.) of southern Africa-Nata s.s. and Natella (Mollusca: Gastropoda: Rhytididae), with description of three new species. AB - This paper represents the second part of our revisionary studies on the rhytidid fauna of southern Africa. The species discussed belong to the taxon Nata s.l. in which we recognise two genus-level lineages, Nata s.s. and Natella with six (three new) and one species respectively. We update the species-level taxonomy extensively in the light of new molecular and morphological data, and provide a comprehensive revision of all species, including keys. Detailed comparative morphological observations are provided for the distal reproductive tract, pulmonary cavity, mantle edge, radula and suprapedal gland. In addition, we present a summary of biological and ecological data including information on habitat preferences, feeding, prey items and mating behaviour. Although the two genera are well circumscribed in terms of both internal anatomy and molecular data, shell morphology is highly conserved, and species discrimination using shell characters alone is difficult. We have discovered three undescribed species within Nata and there is evidence that further research of a phylogeographic nature may uncover additional cryptic diversity. The geographic distributions of the species are discussed in relation to regional vegetation patterns and, as with the larger cannibal snail radiation, the Albany Thicket Biome emerges as a focus of endemism. Observations on the conservation status of all species are provided.New species: Nata aequiplicata sp. nov., Nata erugata sp. nov. and Nata watsoni sp. nov. Revised status: Natalina caffrula Melvill & Ponsonby, 1898 is transferred to the genus Nata and thought to be a synonym of Nata dumeticola (Benson, 1851). PMID- 27394521 TI - A synopsis of the Family Cordagalmatidae fam. nov. (Cnidaria, Siphonophora, Physonectae). AB - The genus Cordagalma is reviewed and a re-description given of one of the extant species, C. ordinatum (Haeckel). In addition, four new species are described in the genus Cordagalma, namely C. abyssorum sp. nov., C. bimaculatum sp. nov., C. isocarrei sp. nov. and C. rugosum sp. nov. All these species have similar larval type tentilla. A fifth new species, which has extraordinary tentilla, with an involucrum forming two flaps, is placed in a new genus Cardianecta gen. nov. as C. parchelion sp. nov. The significant differences that all these species have from other physonects is considered to warrant the establishment of the family Cordagalmatidae fam. nov. for them. This family is diagnosed purely on the presence of heart-shaped nectophores budded on the ventral side of the nectosome. PMID- 27394522 TI - Discovering the still unexplored arachnofauna of the National Park of Dadia Lefkimi-Soufli, NE Greece: a taxonomic review with description of new species. AB - The National Park of Dadia in NE Greece (Thrace) was established as a nature reserve in 1980, mainly due to its great diversity in birds of prey. Since then many studies have taken place, focusing on other birds, reptiles, amphibians and some invertebrates (grasshoppers, beetles and butterflies), but up to now none was conducted on spiders. The aim of the present paper was to create the first extensive checklist on the spiders of this important natural reserve. For this purpose, pitfall traps were set in 15 sites located in and around the National Park, resulting in a large spider collection. The results of the taxonomical revision of this collection are here presented, giving rise to 132 species in total, which belong to 24 families. Of them, 11 species (Centromerus valkanovi Deltshev, 1983, Crosbyarachne silvestris (Georgescu, 1973), Ipa terrenus (L. Koch, 1879), Sintula spiniger (Balogh, 1935), Tenuiphantes floriana (van Helsdingen, 1977), Alopecosa taeniopus (Kulczynski, 1895), Liocranum rupicola (Walckenaer, 1830), Zodarion turcicum Wunderlich, 1980, Gnaphosa modestior Kulczynski, 1897, Philodromus krausi Muster & Thaler, 2004, Cozyptila thaleri Marusik & Kovblyuk, 2005) are new records for the Greek territory. Seven species (Dysdera kati sp. n., Dysdera krisis sp. n., Harpactea ice sp. n., Harpactea wolfgangi sp. n.-Dysderidae, Phrurolithus thracia sp. n.-Phrurolithidae, Zodarion beroni sp. n.-Zodariidae, Drassyllus dadia sp. n.-Gnaphosidae) are here proposed as new species for science. PMID- 27394523 TI - An illustrated catalogue of type specimens of the bathyal brittlestar genera Ophiomusium Lyman and Ophiosphalma H. L. Clark (Echinodermata: Ophiuroidea). AB - Type specimens of 61 species of the bathyal ophiuriod genera Ophiomusium Lyman and Ophiosphalma H.L. Clark are illustrated and their main features outlined, to form a partial catalogue for current and future workers. Thirty-nine species of Ophiomusium and 22 of Ophiosphalma are recognised, based largely on the number of exposed tentacle pores on the basal ventral arm plates. Most of the Ophiosphalma listed here are new combinations from their original genus, Ophiomusium. Ophiomusium sculptum Verrill is a junior subjective synonym of O. acuferum Lyman, and Ophiosphalma fimbriatum (Koehler) is a junior subjective synonym of O. glabrum (Lutken & Mortensen). The subspecies Ophiomusium fimbriatum atlanticum Hertz and Ophiomusium facunda muta Hertz are elevated to full species. Because of their bathyal habitat (<4000 m), representatives of these genera are relatively rare in collections, and it will require fresh material of a range of sizes, for morphological comparison and for DNA analysis, to reliably confirm their taxonomic validity and clarify their relationships. PMID- 27394524 TI - Bryophyte-feeding of Litoleptis (Diptera: Rhagionidae) with descriptions of new species from Japan. AB - Here we report the larval phytophagous habit of Litoleptis for the first time, and describe six new species of Litoleptis in Japan; L. japonica n. sp., L. kiiensis n. sp., L. niyodoensis n. sp., L. himukaensis n. sp., L. izuensis n. sp., and L. asterellaphile n. sp. All the species described here are thallus miners of liverworts belonging to Aytoniaceae and Conocephalaceae (Marchantiopsida: Marchantiophyta). Each fly species mined thalli of only one of the following genera: Conocephalum, Reboulia, and Asterella. The descriptions of the Japanese Litoleptis species here expand the concept of this genus. The female genital morphology of Litoleptis strengthened the current placement of Litoleptis as a member of Spaniinae. PMID- 27394525 TI - Taxonomy of intertidal cheilostome Bryozoa of Maceio, northeastern Brazil. Part 1: Suborders Inovicellina, Malacostegina and Thalamoporellina. AB - Thirteen cheilostome bryozoan species from intertidal habitats of Maceio, Alagoas State, Brazil, are reported here. We describe four new species: Aetea cultrata n. sp., Biflustra marcusi n. sp., Biflustra sphinx n. sp. and Jellyella brasiliensis n. sp. Two other species of Inovicellina, Aetea arcuata Winston & Hayward, 2012, and Aetea curta Jullien, 1888, and four species of Malacostegina, Arbocuspis bellula (Hincks, 1881), Arbocuspis bicornis (Hincks, 1881), Arbocuspis ramosa (Osburn, 1940), and Jellyella tuberculata (Bosc, 1802), are reported on drift algae. Three species of Thalamoporellina are found for the first time in Maceio, Labioporella tuberculata Winston, Vieira & Woollacoot, 2014, Steginoporella magnilabris (Busk, 1854) and Thalamoporella floridana Osburn, 1940. PMID- 27394526 TI - Taxonomic revision of Australian long-horn moths of the genus Nemophora (Lepidoptera: Adelidae). AB - The taxonomic revision of Australian species of the genus Nemophora Hoffmannsegg is based on investigation of type materials of all described taxa. Lectotypes are designated for Nemotois opalina Meyrick, 1912; N. panaeola Turner, 1913; N. sparsella Walker, 1863; N. topazias Meyrick, [1893]; N. orichalcias Meyrick, [1893]; and N. selasphora Turner, 1913. N. topazias Meyrick, syn. nov. and N. selasphora Turner, syn. n. are synonymized with Nemophora laurella (Newman, 1856). Two new species, Nemophora doddi sp. nov. and N. turneri sp. nov., are described from Queensland. The fauna of Australia currently includes seven valid species of Nemophora, which form a monophyletic laurella species-group. Keys to species based on external characters and on male genitalia are provided; adults and male genitalia are described and illustrated. PMID- 27394527 TI - Pseudobiceros wirtzi sp. nov. (Polycladida: Cotylea) from Senegal with revision of valid species of the genus. AB - The genus Pseudobiceros was established based on the presence of two male gonopores, duplicated male reproductive structures, smooth dorsal surface, complex folded pseudotentacles, and simple ruffled pharynx. We describe here a new species of Pseudobiceros from the African continent that has been repeatedly reported and photographed over the years, but lacked a formal description. Pseudobiceros wirtzi sp. nov. is described based on morphological and histological characters. Our bibliographical revision of the genus considers 39 species to be valid. We applied the diagnostic characters of Pseudobiceros to Pseudoceros species listed before the split between these genera, and to species listed as incertae sedis. Pseudobiceros punctatus (Laidlaw 1902) nov. comb. shows typical features of Pseudobiceros. We also discuss other species with historically conflictive generic placements or problematic synonymy and summarize distributions and species characteristics in a comparative table. Most Pseudobiceros species still need re-descriptions to fill gaps regarding internal and pharynx details. Further sampling on the Eastern Africa coast and on mid Atlantic Islands should prove useful in getting a general view of polyclad biodiversity and biogeography in the Tropical and South Atlantic. PMID- 27394528 TI - Euparatettix dandakaranyensis sp. nov. (Tetrigidae: Tetriginae)-a new pygmy grasshopper species from Central India. AB - Euparatettix dandakaranyensis Gupta sp. nov. is described from Bastar, Chhattisgarh, India. A brief comparison with the type specimen of Euparatettix sikkimensis (Hancock, 1915) formerly placed within the genus Xistra is given. A key to the species of the genus Euparatettix known from the Indian subcontinent is provided. PMID- 27394529 TI - Replacement names for two preoccupied generic names in Arthropoda. AB - The genus Ransonia Blandin, 1979 (Arachnida: Araneae) was established with description of a new species, Ransonia mahasoana of the family Pisauridae (Arachnida: Araneae) endemic from Mahasoa, Madagascar. Unfortunately, this name is preoccupied by Ransonia Kramp, 1947, a genus of the family Rhopalonematidae (Hydrozoa: Trachymedusae) with only one species, Ransonia (Aglantha) krampi Ranson (1932), from Gibraltar, Mediterranean. According to article 60 of the International Code of Zoological Nomenclature a new substitute name is necessary, since Ransonia Blandin, 1979 does not have a junior synonym applicable and is a junior homonym of another genus. Therefore, we propose a replacement name for the spider genus as follows. PMID- 27394530 TI - Colasposoma dauricum Mannerheim, 1849 an Asian species adventive to Piedmont, Italy (Coleoptera: Chrysomelidae: Eumolpinae). AB - Colasposoma dauricum Mannerheim, 1849, a species native to the Eastern Asia, is newly found in Piedmont-Italy. This discovery constitutes the first report of the species from Europe, as well as its first report from outside the original area. The general habitus of the species, the distribution in Italy based on the current knowledge, ecological notes and a reference cox1 gene sequences are reported in the present note. PMID- 27394531 TI - Review of terminology for the outline of dorsal scutum in Laniatores (Arachnida, Opiliones). AB - In many Opiliones (notably the Laniatores) the five most anterior opisthosomal tergites are fused with the carapace forming the so called dorsal scutum (DS) (Latreille 1804; Simon 1879; Hadzi 1942) with a highly variable shape arising from multiple factors, such as differential development of musculature (especially of coxa IV), internal organs and influence of appendages (Loman 1903; Winkler 1957). The different degrees of fusion of the tergites were first studied by Hadzi (1942), who proposed a terminology for them. This terminology was adopted and enhanced by Kratochvil (1958) and Martens (1978). A shield formed by the fusion of the carapace with abdominal tergites I to V is called scutum magnum (Hadzi 1942). The shield formed by the fusion of carapace with abdominal tergites I to VII is called scutum complexum (Kratochvil 1958) and occurs in the males of Heteropachylinae Kury, 1994 (Kury 1994) and Paralolidae Kratochvil, 1958 (Kratochvil 1958). Finally, the scutum completum (Hadzi 1942) is formed by the complete fusion of the carapace and abdominal scutum, formed by tergites I to VIII, and occurs in the Sandokanidae (Martens 1978). In this paper we focus on the different forms of the scutum magnum. PMID- 27394532 TI - A new species of Fansipaniana from Northern Vietnam (Lepidoptera: Tortricidae: Olethreutinae: Olethreutini). AB - Vietnam micro-moths remain poorly known, and new species are discovered year after year among the Tortricidae (Kuznetzov 1992, 2000; Razowski 2003, 2008; Heppner 2010; Heppner and Bae 2015a, b) and other families (e.g., Park et al. 2007). Razowski (2009) described the genus Fansipaniana for a single new species from the high mountains in northern Vietnam close to the border with China. Recent exploration of many areas in Vietnam has resulted in the discovery of a second species of Fansipan-iana from a lower elevation mountain range near Hanoi. The new species is from Tam Dao, one of the most well known sites in Vietnam for moth collecting. PMID- 27394533 TI - Pseudolycoriella skusei sp. nov. (Diptera: Sciaridae), a new dark-winged fungus gnat from Norfolk Island and Australia. AB - The genus Pseudolycoriella Menzel & Mohrig, 1998 is distributed worldwide and especially species rich within the southern hemisphere. Within the Australasian region it is known from New Zealand (Mohrig & Jaschhof 1999; 5 species), New Caledonia (Kohler & Menzel 2013; 14 species) and Papua-New Guinea (Mohrig 2013; 22 species). Here we report the first records of the genus from Norfolk Island and Australia. PMID- 27394534 TI - Discovery of a new species and key to all known species of the genus Aalatettix Zheng & Mao (Orthoptera, Tetrigoidea, Tetrigidae) from China. AB - The genus Aalatettix Zheng & Mao, 2002 (Orthoptera, Tetrigoidea, Tetrigidae) contains 9 valid species in China (Zheng & Mao, 2002; Zheng, Cao & Chen, 2011; Zheng, Lin & Zhang, 2013; Zheng, 2014a; Zheng, 2014b; Zheng & Lin, 2015; Zheng, Shi & Yin, 2015). During the identification of pygmy grasshopper specimens collected from Taiwan, China in 1998, a new species of the genus Aalatettix Zheng & Mao, 2002 was found and described below. A key to all known species of the genus is given in this paper. The type specimens are deposited in the National Museum of Natural Science, Taichung, Taiwan, China. PMID- 27394535 TI - Stenichnus lackneri sp. n. of Japan (Coleoptera, Staphylinidae, Scydmaeninae). AB - Stenichnus Thomson, 1859 is a species-rich and common genus in the western Palaearctic, but only a few species are known from the Far East. Six species have been so far recorded from Japan (Sharp 1886; Jaloszynski 2004, 2006; Jaloszynski, Arai 2009). Interestingly, the Japanese species occur in the temperate or cool climate of Hokkaido in the north-east (Stenichnus minipollens Jaloszynski, 2004) and in subtropical forests of the south-western Yaeyama Archipelago (St. bellulus Jaloszynski, 2004 and St. totoro Jaloszynski, 2004), showing a broader range of ecological plasticity than their western Palaearctic congeners. Two more species are known to occur in the Japan mainland, i.e., St. pollens (Sharp, 1886) in Kyushu and St. sakurayamanus Jaloszynski & Arai, 2009 in the central part of Honshu, and one species, St. mitai Jaloszynski, 2006, was discovered on the small Nakanoshima Island of the Tokara Archipelago. Only the species that occur in the Yaeyama Islands are relatively common, all remaining species are known from holotypes only. Interestingly, St. pollens and St. minipollens, which occur on different islands separated by nearly 1500 km, share very similar aedeagi with a unique long ventral projection (Jaloszynski 2004). PMID- 27394536 TI - The Tenuipalpidae of Turkey, with a key to species (Acari: Trombidiformes). AB - A new Turkish species of Tenuipalpidae, Aegyptobia juniperi sp. nov., is described and seven previously recorded species are redescribed: Aegyptobia beglarovi Livshitz & Mitrofanov 1967, Brevipalpus rotai Castagnoli & Pegazzano, 1979, Cenopalpus bagdasariani (Livshitz & Mitrofanov, 1970), Cenopalpus bakeri Duzgunes, 1967, Phytoptipalpus salicicola (Al-Gboory, 1987), Tenuipalpus granati Sayed, 1946 and Tenuipalpus punicae Pritchard & Baker, 1958. A key to the 28 species of Tenuipalpidae from Turkey is provided. Cenopalpus bagdasariani, B. rotai and A. beglarovi are new records for Turkey. PMID- 27394537 TI - Cicadas (Hemiptera: Cicadidae) from Camiguin of Mindanao Province and Dinagat Island in the Philippines, with a new genus and three new species. AB - This paper provides the first faunal checklist for the family Cicadidae (Hemiptera) from Camiguin of Mindanao Province and Dinagat Island in the Philippines, comprising ten species belonging to nine genera. Cryptotympana shillana Lee & Mohagan sp. nov., Orientopsaltria inermis (Stal, 1870), Purana crassinotata Lee, 2015, and Huechys parvula Haupt, 1924 are recorded for the first time from Camiguin. Platypleura dinagatensis Lee sp. nov., Chremistica kyoungheeae Lee, 2010, Dundubia vaginata (Fabricius, 1787), Oncotympana pallidiventris Stal, 1870, and Philipsalta nigrina Lee, Marshall & Hill sp. nov. are newly recorded from Dinagat Island. A new genus Philipsalta Lee, Marshall & Hill gen. nov. is erected. Huechysini Distant, 1905 syn. nov. is synonymized with Cicadettini Buckton, 1889. Information on geographic distributions of the Camiguin and Dinagat species is also provided. PMID- 27394538 TI - New species of microcaddisflies from China (Trichoptera: Hydroptilidae). AB - Five new species of hydroptilids in four genera are described from China, including three new species in Hydroptilinae: Agraylea dactylina n. sp., Allotrichia rhynchophyllum n. sp., and Microptila hamatilis n. sp.; and two new species in Stactobiinae: Stactobiella mutica n. sp. and Stactobiella parallelica n. sp. New records are given for Stactobiella biramosa Martynov 1929 and Pseudoxyethira thingana (Olah) 1989. Genera Agraylea, Allotrichia, Stactobiella, and Microptila are new to Chinese fauna. PMID- 27394539 TI - New American Lamiinae (Coleoptera, Cerambycidae). AB - Five new species are described in Lamiinae: Cotycicuiara v-alba (Acanthoderini), from Brazil (Bahia); Dolichestola birai, from Argentina, and D. monnei, from Brazil (Rio de Janeiro) and Uruguay (Desmiphorini); Blabicentrus lineatus, from Brazil (Rio de Janeiro) (Desmiphorini); and Inermestoloides flavus, from Brazil (Para) (Desmiphorini). A key to species of Cotycicuiara is provided; Blabicentrus lineatus is included in a previous key. PMID- 27394540 TI - Description of a new species of Victoriopisa Karaman & Barnard, 1979 (Crustacea: Amphipoda: Eriopisidae) from China, with a key to the genus Victoriopisa. AB - Victoriopisa multiartus sp. nov. is described from mangrove in Qi'ao Island, China. The new species differs from the other nine species of the genus Victoriopisa in the gnathopod I sexual dimorphism; propodus palm of gnathopod II with two excavations in female and one excavation in male; and terminal article of outer ramus in uropod III expanded, oval-shaped. A key to the genus Victoriopisa with ten species and a map of their distribution are provided. PMID- 27394541 TI - Karawajew's ant type specimens (Hymenoptera, Formicidae) in the National Museum of Natural History of the National Academy of Sciences of Ukraine. AB - The collection of W.A. Karawajew is one of the richest and most famous ant collections of the World. Much of this collection consists of dry mounted specimens, including types of about 550 taxa, housed in the Shmalhausen Institute of Zoology of the National Academy of Sciences of Ukraine (Kiev). Nevertheless, we located a considerable part of Karawajew's collection, containing about 25,000 specimens in alcohol, that is preserved in the National Museum of Natural History of the National Academy of Sciences of Ukraine (Kiev). The latter material was recently examined and we found types of 24 taxa. This type material was partly mounted, re-ordered and catalogued. In this paper we present a catalogue of these type specimens housed in the National Museum of Natural History. PMID- 27394542 TI - Taxonomic revision of some Micromyinae (Diptera: Cecidomyiidae) described by Zoya L. Berest. AB - The taxonomy of 13 Micromyinae (Cecidomyiidae) described by Zoya L. Berest in 1986-2001 is revised. As a result, 12 new junior subjective synonyms are proposed: Aprionus giganteus Berest, 1991 syn. nov. of Aprionus halteratus (Zetterstedt, 1852); Aprionus lobatus Berest, 1986 syn. nov. of Aprionus acutus Edwards, 1938; Aprionus onychophorus Berest, 1991 syn. nov. of Aprionus cardiophorus Mamaev, 1963; Bryomyia multispinata Berest, 1988 syn. nov. of Bryomyia gibbosa (Felt, 1907); Cordylomyia barsovi Berest, 1991 syn. nov. of Neurolyga fenestralis Rondani, 1840; Eleniella Berest, 2001 syn. nov. of Monardia Kieffer, 1895; Eleniella kyseluci Berest, 2001 syn. nov. of Monardia obsoleta Edwards, 1938; Heterogenella dolini Berest, 1989 syn. nov. of Heterogenella cambrica (Edwards, 1938); Peromyia almensis Berest, 1989 syn. nov. of Peromyia caricis (Kieffer, 1901); Peromyia emarginata Berest, 1988 syn. nov. of Peromyia fungicola (Kieffer, 1901); Peromyia paliformia Berest, 1994 syn. nov. of Peromyia aeratipennis (Skuse, 1888); and Peromyia podolica Berest, 1991 syn. nov. of Peromyia fungicola (Kieffer, 1901). Misinterpretation of preparation artifacts for taxonomic characters is shown to be the principal reason for the identification errors unveiled here. Peromyia extensa Berest, 1991, a valid species known only from the type specimens, is redescribed. PMID- 27394543 TI - Three new species of Leptoceridae Leach 1815 (Insecta: Trichoptera) from Shan State, Myanmar. AB - Three new species of Leptoceridae, including Ceraclea satasookae n. sp., Setodes siribumrungsukhai n. sp., and S. salweenensis n. sp. are described and figured from Shan State, Myanmar. Twenty-two species of Leptoceridae were found and 21 of them are new records to the country. PMID- 27394544 TI - First Record Of The Order Mecoptera (Insecta) For The Gorgona Island (Colombia), With The Description Of A New Species. AB - During a review of material from the project "Assessment of the current status of the faunistic conservation objects from the Gorgona Island: a holistic approach to the ecological evaluation of the Gorgona Natural National Park", conducted 2010-2011, a male specimen of Pazius Navas, 1913 (Mecoptera: Bittacidae) was found. The genus had been previously recorded in Colombia in the Amazonas and Cundinamarca departments. The specimen described here differs from other species of Pazius by the absence of the aedeagus ventral process, the presence of seven short dorsal spines at the epandrium and shape of the ventral process. This finding represents the first record of the order Mecoptera for Gorgona Island, a new species of Pazius, and the expansion of the genus distribution in Colombia. A detailed morphological description of Pazius gorgonensis n. sp. and an identification key for species of the genus are presented. PMID- 27394545 TI - A new pygmy grasshopper species (Tetrigidae: Tetriginae) from Central India. AB - Ergatettix subtruncatus sp. nov. is described from Durg district of Chhattisgarh, India. The new species is similar to Ergatettix callosus (Hancock, 1915), but differs from the latter by frontal cost bifurcation starts at the level of upper margin of compound eyes; median carina of vertex indistinct; posterior angle of lateral lobes of pronotum not broad, apex subtruncate, narrow; mid femur slender with small white hairs and 3indistinct lobes; dorsal valve of ovipositor less flattened. A distribution map of Ergatettix subtruncatus sp. nov. and a key to known species of the genus Ergatettix Kirby, 1914 from the Indian subcontinent is provided. The type specimens are deposited in the Central Entomological Laboratory (CEL), Zoological Survey of India, Kolkata. PMID- 27394546 TI - Two new species of Curuapira Martins & Galileo, 1998 (Coleoptera, Cerambycidae, Lamiinae, Desmiphorini). AB - Two new species of Curuapira Martins & Galileo, 1998 are described: C. hovorei sp. nov. from Ecuador and C. armandi sp. nov. from Panama. A key to species of the genus is provided. PMID- 27394547 TI - A note on the biogeographical origin of the brine shrimp Artemia urmiana Gunther, 1899 from Urmia Lake, Iran. AB - The brine shrimp Artemia urmiana, an abundant inhabitant of the hypersaline Urmia Lake in northwestern Iran, has recently been described from Lake Koyashskoe, also a shallow hypersaline lake that is located on the Black Sea coast of the Crimean Peninsula (Ukraine). This discovery has questioned the endemicity of A. urmiana in Urmia Lake and has also brought into question the biogeographical origin of this species. In the present study, we combined recent genetic divergence data (mtDNA-COI) with palaeoecological evidence to address the biogeographical origin of A. urmiana. Calibration of the molecular clock of the COI region was set by assigning the age of the micro-crustacean Daphnia pulex minimally at 145 Mya. The divergence age of A. urmiana in Urmia Lake dates back to 383,000 years, whereas Ukrainian Artemia reflects a very young populations that diverged about 196,000 years ago. Palaeoecological evidence suggests that the age of the major habitat of A. urmiana i.e. Urmia Lake goes back to the Tertiary Period while the Ukranian habitats of the species are very young, by virtue of geological features of the Holocene age. We conclude that the biogeographical origin of A. urmiana is outside of Europe and the current state of knowledge strongly suggests that Urmia Lake has been the major source of its expansion into its modern habitats in Europe. PMID- 27394548 TI - Five species of the family Cyproideidae (Crustacea: Amphipoda) from Japan, with the description of a new genus and two new species. AB - Five species of the family Cyproideidae (Crustacea: Amphipoda) are described from shallow sea in Japan. Cyproidea liodactyla Hirayama, 1978 was collected from Kanagawa and Shizuoka Prefectures and Ariake Sea. Morphological character of the antenna 1 in these specimens is different from the original description. Examining the paratypes of C. liodactyla, the shape of the antenna 1 in the holotype is revealed to be abnormal. Cyproidea okinawensis sp. nov. was collected from Okinawa Island. Its morphological characters resemble C. liodactyla and C. robusta Ren, 2006; however, this new species is different from the former in the smaller eyes, the narrower coxa 5 and the coloration, and from the latter in the ovoid telson. Metacyproidea gen. nov. is established with M. makie sp. nov. from Hachijo Island in Tokyo Prefecture as its type species. This new genus resembles Cyproidea, especially in the peduncular article 2 of antenna 1 with a distinct distal tooth and the posterodorsal end of urosomites with a strong projection. However, Metacyproidea can be distinguished from Cyproidea by the coalesced urosomites 2-3 and the antenna 1 with a 10-16-articulated flagellum. Moolapheonoides acutifalcatus Kobayashi & Ishimaru, 2005 and Terepeltopes dolichorhunia Hirayama, 1983 were also collected from Wakayama and Fukui Prefectures and Kanagawa, Shizuoka and Yamaguchi Prefectures, respectively. A key to species of the family Cyproideidae in Japan is provided. PMID- 27394549 TI - Taxonomic and nomenclatorial revision within the Neotropical genera of the subtribe Odontocheilina W. Horn in a new sense-15. The genus Opisthencentrus W. Horn (Coleoptera: Cicindelidae). AB - The Neotropical, monobasic tiger beetle genus Opisthencentrus W. Horn, 1893, based on Oxygonia dentipennis Germar, 1843, is presented along with a lectotype designation. Most of the diagnostic characters of Opisthencentrus dentipennis (Germar, 1843), including the aedeagus and structures of the internal sac, are illustrated for the first time. Redescription and illustrations in colour photographs of the habitus and diagnostic characters of the female lectotype (MFNB) and five other specimens of both sexes are provided. The validity of Opisthencentrus as a separate genus is confirmed and it is concluded that the genus is a natural member of the subtribe Odontocheilina W. Horn, 1899, markedly differing from the genus Oxygonia Mannerheim, 1837. The history of the taxonomy and relationship to other genera of the subtribe, as well as the biology and distribution of this very rare and hitherto little known tiger beetle in the Brazilian Atlantic rain-forest, are discussed. PMID- 27394550 TI - A new species of Coryogalops (Perciformes: Gobiidae) and the first adult record of Feia nympha from the Red Sea. AB - A new species of the gobiid genus Coryogalops, C. nanus sp. nov. is described from the Red Sea. Coryogalops nanus sp. nov. is distinguished from congeners in having dorsal-fin rays VI + I,10; anal-fin rays I,9; pectoral-fin rays 12-14 (lowest count known for the genus), two upper rays with free tips; pelvic fins I,5, joined to form an emarginate disc, no pelvic frenum; predorsal area and narrow area at base of first dorsal fin naked; longitudinal scale series 26-29; transverse scale rows counted forward 6-7; transverse scale rows counted backward 7-8; circumpeduncular scale rows 11-12; seven transverse suborbital rows of sensory papillae; no tentacle above upper eye margin; anterior nostril tubular, without flap at its tip, posterior nostril pore-like; body semitranslucent, covered with small scattered orange-yellow spots and speckles, those in predorsal area contain black dots; an internal row of white spots along ventral part of body above anal-fin base and on caudal peduncle; head with small scattered orange to yellowish brown spots; first dorsal fin with two broad white bands at base of fin and distally, and with hyaline area densely dotted with melanophores in the middle of fin; preserved specimens opaque white to yellowish with sparse melanophores. An adult specimen of Feia nympha is recorded for the first time in the Red Sea and the lateral line system of this species is described. PMID- 27394551 TI - Three new species of Laonice (Polychaete: Spionidae) from West and Southwest Africa. AB - Three new species of Laonice (Polychaete: Spionidae): L. galatheae, L. cricketae, L. olgae-are described from South and West Africa (along the coast from 31 degrees 14.1'S to 04 degrees 44'N) based on Danish and South African zoological collections. Arguments relative to the morphological heterogeneity of the genus Laonice are advanced. The arguments are based on the following characters: degree of fusion of prostomium with peristomium at the anterior margin, degree of variability of all numerical characters, arrangement of anterior capillaries in two or more vertical rows, presence or absence of transversal dorsal membranous crests in the "post nuchal organ" and presence of genital pouches only on very limited number of segments or other pattern. Authors think it is obvious today an existence of at least four morphologically separate groups of species inside the Laonice-genus: "L. cirrata", "L. sarsi", "L. appelloefi" and "L. norgensis" groups. Eight species names from 34 valid names in the genus are still with unclear affiliation. L. quadridentata is treated now as a junior synonym of L. brevicornis. An opinion is expressed about L. insolita not belonging to the genus Laonice because of discrepancy the generic diagnosis. PMID- 27394552 TI - The genus Triomicrus Sharp from central and southwestern China (Coleoptera: Staphylinidae: Pselaphinae), and a revised key to the Chinese species. AB - Five species of the genus Triomicrus Sharp from central and southwestern China are recognized, two of them are described as new: T. mangshanensis sp. n. from Hunan, and T. nabanhensis sp. n. from Yunnan. New distributional records for T. ludificator Lobl, Kurbatov & Nomura, T. mirus Shen & Yin, and T. punctifrons Lobl, Kurbatov & Nomura are given. A revised key to the Triomicrus species of China is presented. PMID- 27394553 TI - Taxonomic status of the genera Amphipholizona H.L. Clark, 1915
(Ophiuroidea, Ophiolepididae) and Amphigyptis Nielsen, 1932 (Hemieuryalidae): systematic placement and synonymy. AB - We synonymize Amphipholizona (Ophiolepididae) and Amphigyptis (Hemieuryalidae), suggest their transfer to family Amphiuridae, and propose a new species combination (Amphipholizona perplexa new comb.). We further provide a new diagnosis for the genus Amphipholizona, a dichotomic identification key for the two species now belonging to this genus and re-describe and illustrate for the first time some of the internal characters, such as the genital plates, vertebrae, and inner side of the lateral arm plate. PMID- 27394554 TI - Two snakes from eastern Australia (Serpentes: Elapidae); a revised concept of Antaioserpens warro (De Vis) and a redescription of A. albiceps (Boulenger). AB - Antaioserpens warro sensu lato is known from two populations, one in north eastern Queensland (Qld), the other from south central Qld. Morphological and genetic assessments demonstrate that these widely separated populations represent two species. A re-examination of museum specimens and the type descriptions show that the name A. warro (De Vis) has been erroneously applied to the north-eastern Qld species. The type specimen of A. warro, from the Gladstone district in south east Qld, is badly faded but the colour pattern as described by De Vis (1884a) is consistent with that of recently collected specimens from south central Qld and it is this species to which the name applies. The earliest available name for the species from north-eastern Qld is A. albiceps (Boulenger, 1898). Both A. warro and A. albiceps are redescribed herein. PMID- 27394555 TI - Contribution to the knowledge of the genus Neuraphes Thomson (Coleoptera: Staphylinidae: Scydmaeninae) in China. AB - Two new species of the ant-like stone beetle genus Neuraphes Thomson, 1859 (Scydmaeninae: Glandulariini) from Sichuan Province are described: N. (Pararaphes) shu sp. n. and N. (Pararaphes) xilingensis sp. n., their aedeagi are illustrated. A single female of the nominotypical subgenus from Heilongjiang Province is also recorded. PMID- 27394556 TI - Studies of Peruvian Ptiliidae (Coleoptera) 3: the genus Discheramocephalus Johnson including six new species, and validation of the unavailable generic name Phytotelmatrichis Darby and Chaboo. AB - Six new species of Discheramocephalus Johnson are described and figured: D. angustus sp. n., D. capac sp. n., D. inretitus sp. n., D. interfusus sp. n., D. malalae sp. n. and D. parvus sp. n.. The insects were collected by Dr Caroline Chaboo and her students at the University of Kansas as part of a programme to compile an inventory of leaf beetles in Peru and are the first records of the genus from the country. A key is provided. The unavailable genus Phytotelmatrichis Darby & Chaboo is made available from this publication, with Phytotelmatrichis peruviensis Darby & Chaboo 2015 as its type species. PMID- 27394557 TI - Turritopsis fascicularis Fraser, 1943 (Cnidaria: Hydrozoa): redescription and discussion of its phylogenetic position within the genus. AB - Turritopsis fascicularis Fraser, 1943 was first described off Alligator Reef, Florida, USA, at a depth of 216 m. Presumably a deep-sea species, its validity has often been questioned due to the scarcity of available records. In this paper, T. fascicularis is re-described from some mature colonies from the upper slope of the Gulf of Mexico. Furthermore, new pictures of the colony, polyps, and medusa buds, are provided. A ~600bp sequence of the large ribosomal subunit of the mitochondrial RNA (lsu-rRNA, 16S), also known as the Hydrozoan barcoding molecule, is used for the first time to confirm the validity of T. fascicularis as a species, and analyze its phylogenetic position within the genus Turritopsis. PMID- 27394558 TI - A new genus and species of troglobitic ground beetle from eastern Guizhou, Southwest China (Coleoptera: Carabidae: Trechinae). AB - Tianzhuaphaenops jinshanensis n. gen., n. sp. is described from a limestone cave called Jinshan Rongdong in the easternmost Guizhou Province of Southwest China. This troglobitic trechine genus is related to Guizhaphaenops- Qianotrechus- Qianaphaenops complex but its precise position remains undetermined. PMID- 27394559 TI - Two new species of scale worms (Polychaeta: Aphroditiformia) from deep-sea habitats in the Gulf of Cadiz (NE Atlantic). AB - Two new species of scale worms are described from the Gulf of Cadiz (NE Atlantic), at depths between 1100 and 2230 m. Australaugeneria iberica sp. nov. (Polynoidae) was obtained from an alcyonarian colony collected at the flank of Carlos Ribeiro mud volcano; it is characterized by the presence of neuropodial hooks only on segment two and by having the first parapodia not enlarged. This is the first report of the genus for the deep sea. The diagnosis of Australaugeneria is emended and a table comparing all species of the genus is provided. Pholoe petersenae sp. nov. (Pholoidae) was collected from the crater of three mud volcanoes (Darwin, Captain Arutyunov and Carlos Ribeiro) in areas of active seepage. This species is characterized by the presence of prostomial peaks and parapodia stylodes and the absence of eyes. PMID- 27394560 TI - Lichenophilous species of Epidamaeus and Spatiodamaeus from high mountains of Mongolia, with remarks on their ontogeny (Acari: Oribatida). AB - Herein, the description of the adults and immature instars of a newly discovered species, Epidamaeus munkhbayari sp. nov. along with detailed illustrations and data on habitat ecology are provided. Adults of this new species can be easily distinguished form other known species of Epidamaeus by the combination of following characters: two pairs of well-developed prodorsal ridges, the presence of ventral tubercles E2a, Va and Vp, the short, thin interlamellar setae, and the strongly developed tectum of podocephalic fossa. Further, the redescription of adults and morphology of deutonymph of a little known species, Spatiodamaeus cf. fageti Bulanova-Zachvatkina, 1957, which is recorded for the first time in Asia, are given. The diagnosis of the latter species is modified and enriched with the characters of deutonymph. Following the descriptions and comparisons, we discuss aspects of the distribution and ecology of both studied species. Comparative characteristics of juveniles of different species belonging to Epidamaeus and Spatiodamaeus are performed, and the extended discussion on the immature morphology of Damaeidae is provided. Based on the comparative analyses, it can be generalized that the juvenile morphologies of not only Epidamaeus and Spatiodamaeus, but also those of other genera of the family are very similar, and hence, they differ from one another only by a few features, such as the body size, length of setiform organs, such as sensilli, interlamellar as well as gastronotic setae, structure and location of gastronotic cornicles. Epidamaeus munkhbayari sp. nov. is currently known only from the type locality; S. fageti is a Palaearctic species, known from Central and Eastern Europe and Central Asia. Both species appear to be sylvicolous, and primarily inhabitants of lichens growing on tree trunks as well as bare rocks. A list of oribatid mites, inhabiting the lichens growing on tree trunks and bare rocks in a high mountain cool temperate forest together with the two species central to this study, is given. PMID- 27394561 TI - Revision of the genus Araneibatrus (Coleoptera: Staphylinidae: Pselaphinae). AB - The genus Araneibatrus Yin & Li, 2010 is placed as a senior subjective synonym of Tribasodellus Nomura & Yin, 2011, syn. n., resulting in A. callissimus (Nomura & Wang, 1991) comb. n. (= Tribasodellus callissimus). A revised diagnosis and a redescription of Araneibatrus are provided, and the generic limits of Araneibatrus are re-evaluated. Four new species collected in limestone caves are described from China and Laos: A. cellulanus sp. n. (China: Guangdong), A. grossepunctatus sp. n. (China: Hunan), A. pubescens sp. n. (China: Yunnan), and A. spinosus sp. n. (Laos: Oudomxay). All six known species are diagnosed, illustrated, keyed, and mapped. PMID- 27394562 TI - Afrobethylus Ramos & Azevedo, gen. nov., a new remarkable Afrotropical genus of Bethylinae (Hymenoptera: Bethylidae). AB - Afrobethylus Ramos & Azevedo, gen. nov. (type species Afrobethylus zulu Ramos & Azevedo, sp. nov.) with six new species, Afrobethylus antankarana Ramos & Azevedo, sp. nov. (Madagascar), A. antemoro Ramos & Azevedo, sp. nov. (Madagascar), A. bapedi Ramos & Azevedo, sp. nov. (South Africa), A. swazi Ramos & Azevedo, sp. nov. (South Africa), A. vezo Ramos & Azevedo, sp. nov. (Madagascar), A. zulu Ramos & Azevedo sp. nov. (South Africa) are described and illustrated. This genus is characterized by having the antenna with ten flagellomeres; the forewing with second radial cell closed; the female genitalia with dorsal ramus of second valvula broadly enlarged, and the presence of proximal projection starting from the base of second valvifer. A key to the species of Afrobethylus based on females is provided. PMID- 27394563 TI - Another new and threatened species of lancehead genus Bothrops (Serpentes, Viperidae) from Ilha dos Franceses, Southeastern Brazil. AB - A new insular species of the genus Bothrops is described from Ilha dos Franceses, a small island off the coast of Espirito Santo State, in southeastern Brazil. The new species differs from mainland populations of B. jararaca mainly by its small size, relative longer tail, relative smaller head length, and relative larger eyes. The new species is distinguished from B. alcatraz, B. insularis and B. otavioi by the higher number of ventral and subcaudal scales, relative longer tail and smaller head. The new species is highly abundant on the island, being nocturnal, semiarboreal, and feeding on small lizards and centipeds. Due its unique and restricted area of occurrence, declining quality of habitat, and constant use of the island for tourism, the new species may be considered as critically endangered. PMID- 27394564 TI - Megarthrus of southern India and Sri Lanka, with notes on their phylogenetic and biogeographical relationships (Coleoptera: Staphylinidae: Proteininae). AB - South of the Deccan Plateau the genus Megarthrus Curtis was represented so far in the Indian subcontinent only by M. rufomarginatus Cameron, of the hilly areas of Tamil Nadu and Kerala, and Megarthrus bimaculatus Fauvel, of Sri Lanka. Here we describe three additional species from this area: M. nilgiriensis sp. n. and M. narendrani sp. n., both from southern India and strongly resembling M. bimaculatus, and M. lanka sp. n., of Sri Lanka and strongly resembling M. rufomarginatus. The five species of Megarthrus occurring in southern India and Sri Lanka are keyed and illustrated with colour pictures of habitus, genitalia and other main diagnostic characters. They belong to two homogeneous complexes of species-the "bimaculatus-complex" and the "rufomarginatus-complex"-that uniquely share many important features with the Sumatran M. sumatrensis Cameron and the Philippine M. vastus Wendeler, with which they constitute the here defined "vastus-group" of species. The Megarthrus fauna of southern India and Sri Lanka appears thus not only disjunct and completely distinct from that phylogenetically and taxonomically much more diverse of North of the Indo-Gangetic Plain, but also directly related to that of the Sunda shelf. PMID- 27394565 TI - New water mites species (Acariformes: Hydrachnidia) from interstitial waters of the Russian Far East. AB - Illustrated descriptions of three water mite species, Wandesia sokolowi sp. n., Frontipodopsis cuspidata sp. n. and Chappuisides orientalis sp. n. from interstitial waters of the Russian Far East are presented. The male of Wandesia reducta Tuzovskij, 1987 is described for the first time. An identification key of Russian species from the genus Wandesia, based on adults, is given. PMID- 27394566 TI - The larvae of Hydropsyche rhadamanthys Malicky 2001 and Hydropsyche sarpedon Malicky 2001 (Trichoptera: Hydropsychidae), endemics of Crete (South Aegean, Greece), with notes on their ecology. AB - The larvae of Hydropsyche rhadamanthys Malicky 2001 and Hydropsyche sarpedon Malicky 2001, endemics of Crete Island, Greece, are described for the first time. The diagnostic features of the species are described and illustrated, and some information regarding their ecology is included. In addition, diagnostic characters for larvae of the known Aegean Hydropsyche species are provided. PMID- 27394567 TI - Association of the female of Perdita (Xeromacrotera) cephalotes (Cresson), and a replacement name for Perdita bohartorum Parker (Hymenoptera: Andrenidae). AB - The monotypic Perdita subgenus Xeromacrotera Timberlake is currently known only from the male sex. Here, the female of Perdita (Xeromacrotera) cephalotes (Cresson, 1878) is associated, resulting in two new junior synonyms of P. (X.) cephalotes: Perdita (Procockerellia) excellens Timberlake, 1958, new synonym and Perdita (Cockerellia) autumnalis Timberlake, 1977, new synonym. The true number of maxillary palpi are reported, and updated subgeneric and species diagnoses are provided. In addition, Perdita boharti Portman & Griswold, new name, is designated as a replacement name for the primary junior homonym P. bohartorum Parker, 1983 (not P. bohartorum Timberlake, 1956) and is assigned to the related subgenus Cockerellia Ashmead. PMID- 27394568 TI - Coleophora sabina Baldizzone & Tabell, sp. nov. (Lepidoptera: Coleophoridae) from Central Italy. AB - Coleophora sabina sp. nov. is described from Italian mainland. Habitus of the adult and the genitalia of both sexes are illustrated. The species is compared especially to C. fringillella Zeller, 1839. DNA barcodes are shown to be distinct and congruent with morphological differences. PMID- 27394569 TI - Myotrioza myopori Taylor, a designation of the type species for the genus Myotrioza gen. nov. (Psylloidea: Triozidae). AB - Taylor et al. (2016) described twenty new species in one new genus of Australian jumping plant-lice from the plant family Scrophulariaceae but did not nominate a type species, a requirement under the International Code of Zoological Nomenclature under Article 13.3 to make the genus name available (ICZN 1999). PMID- 27394570 TI - First record and a new species of Metopiasoides Comellini (Coleoptera, Staphylinidae, Pselaphinae) from Peru. AB - Metopiasoides jefersoni Asenjo, a new species, of the Neotropical pselaphine tribe Metopiasini, is described from Urubamba Valley in southeastern Peru (Cusco state). Major diagnostic features are illustrated. PMID- 27394571 TI - Notes on the differences between Fredlanea and Eulachnesia, and description of a new species (Coleoptera, Cerambycidae, Lamiinae, Hemilophini). AB - During the process of identification of some specimens sent to the late Ubirajara Ribeiro Martins de Souza by Miguel Angel Monne, we came across some problems involving the genera Fredlanea Martins & Galileo, 1996 and Eulachnesia Bates, 1872. Herein we try to make clearer the differences between those two closely related genera. Actually, only a single good and constant difference could be found between those genera, as shown below. PMID- 27394572 TI - A new Mniotype Franclemont (Lepidoptera, Noctuidae) species from China. AB - The Blepharita Hampson - Mniotype Franclemont-Polymixis Hubner - Mniopamea Hacker & Peks, generic complex is a favourite of Noctuidae researchers due to its richness in evolutional lineages, the debatable taxonomic placement of certain species among the first three genera and the taxonomic interpretation of the genera themselves. This rich and diverse complex includes some fairly separable species of which the taxonomic placement has been changed during the last decades, particularly as a result of the very similar basic configuration of the genitalia. The most relevant comprehensive studies on the generic complex are given by Boursin (1964), Varga (1979), Hacker (1990), Hacker & Peks (1990), Hacker (1992), Hacker & Ronkay (1992), Hreblay & Ronkay (1997, 1998), Hreblay et al. (1998), Hreblay & Ronkay (1999), Ronkay et al. (2001), Benedek & Ronkay (2002). The most recent study on the Mniotype adusta species graup is given by Volynkin et al. (2014), whereas on the Polymixis by Saldaitis et al. (2015). The fourth member of the complex namely Mniopamea, is the latest erected genera, of which the two described species by Hacker (1992) are close relatives of the formerly known Mniotype timida (Staudinger, 1888). PMID- 27394573 TI - Revision of the family Nothybidae (Diptera: Schizophora). AB - The family Nothybidae (Diptera: Schizophora) is revised. The family consists of 11 species in the single genus Nothybus Rondani, which occurs in Papua New Guinea, Nepal and much of the Oriental Region. Three species are described as new: N. absens spec. nov. (China), N. cataractus spec. nov. (Laos, Thailand) and N. procerus spec. nov. (India). Nothybus longithorax Rondani, 1875 is treated as a junior synonym of N. longicollis (Walker, 1856). Nothybus decorus Meijere, 1924 syn. nov. is included as a junior synonym of N. lineifer Enderlein, 1922. PMID- 27394574 TI - Review of the Lispe caesia-group (Diptera: Muscidae) from Palaearctic and
adjacent regions, with redescriptions and one new synonymy. AB - Species of Lispe caesia-group from Palaearctic and adjacent regions are reviewed. Diagnostic characters of this group are updated. One new synonymy is established: L. frontalis Zielke, 1972, syn. nov. for L. leucocephala Loew, 1856. Key to males of ten species (with two subspecies) from Palaearctic, Oriental and Ethiopian regions is given. Nine species (with two subspecies) are photographed. Six species and one subspecies are redescribed. More detailed ultrastructural or external characters for male swollen hind tarsi and the wing interference patterns are also provided. PMID- 27394575 TI - Designation and description of a neotype of Sclerophrys maculata (Hallowell, 1854), and reinstatement of S. pusilla (Mertens, 1937) (Amphibia: Anura: Bufonidae). AB - Molecular analysis indicates that African material previously referred to Amietophrynus maculatus (Hallowell, 1854; now Sclerophrys maculata), is divisible into two distinct clades: a Western Clade from Cameroon westwards and an Eastern Clade from Central African Republic eastwards, and Uganda southwards to South Africa, extending to Angola-Namibia. Preliminary morphological and bioacoustic data support this division. The two clades are recognised here as two separate species. The Western species retains the name S. maculata, with Hallowell's designated type locality of Liberia. The Eastern Clade retains the name published by Mertens (1937), S. pusilla. It is noted that a type specimen of S. maculata cannot be traced and is presumed lost; the so-called syntypes in the Philadelphia Academy of Natural Sciences are not the material described by Hallowell. None of these have been designated as a neotype, consequently a specimen from Liberia in the collection of the Natural History Museum, London, is designated here as the neotype of S. maculata. PMID- 27394576 TI - Description of eleven new species of the goblin spider genus Neoxyphinus Biraben, 1953 (Araneae, Oonopidae). AB - The spiders of the genus Neoxyphinus Biraben differ from those of other oonopid genera by the male endites with an api-cal, retrolateral excavation bearing a subapical tooth-like apophysis and, in females, by the ellipsoid genital atrium, with angular lateral margins. In this paper, eleven new species of the genus are described, mainly from northern South America: N. amazonicus Moss & Feitosa, sp. nov. (??) from Colombia and Brazil; N. macuna Moss & Ruiz, sp. nov. (??), N. tuparro Moss & Ruiz, sp. nov. (?) and N. pure Moss & Bonaldo, sp. nov. (??) from Colombia; N. yekuana Moss & Feitosa, sp. nov. (??), N. trujillo Moss & Bonaldo, sp. nov. (??), N. yacambu Moss & Feitosa, sp. nov. (?) and N. saarineni Moss & Bonaldo, sp. nov. (?) from Venezuela; N. inca Moss & Ruiz, sp. nov. (??) from Peru; N. beni Moss & Feitosa, sp. nov. (??) from Bolivia; and N. coca Moss & Feitosa, sp. nov. (??) from Ecuador. PMID- 27394577 TI - Fossil Megaloptera (Insecta: Neuropterida) from the Lower Cretaceous Crato Formation of Brazil. AB - Two new genera and species of Megaloptera are described from the Lower Cretaceous Crato Formation of Brazil. Cratocorydalopsis brasiliensis gen. et sp. nov. and Lithocorydalus fuscata gen. et sp. nov. are both placed within the family Corydalidae. The specimens represent the first Cretaceous examples of adult megalopteran body fossils not preserved in amber, and are the first megalopterans to be formally described from the Crato Formation. PMID- 27394578 TI - Redescription of the genus Wachsiella (Hemiptera: Heteroptera: Largidae: Physopeltinae) with description of male and comments on its tribal placement. AB - A detailed redescription (including first description of the male sex) of the genus Wachsiella Schmidt, 1931 (Hemiptera: Heteroptera: Largidae: Physopeltinae) and its single species, Wachsiella horsti Schmidt, 1931, is provided. The systematic placement of the genus is discussed and it is placed in the tribe Physopeltini. Wachsiella horsti is a species endemic to south Sulawesi (Indonesia), known only from specimens collected in 1895-1896 and has never been reported since. PMID- 27394579 TI - Review of the grass-feeding leafhopper genera Miradeltaphus Dash & Viraktamath and Yuanamia Zhang & Duan (Hemiptera: Cicadellidae: Deltocephalinae: Deltocephalini). AB - Miradeltaphus Dash & Viraktamath and Yuanamia Zhang & Duan are revised, one new species M. sanogae sp. n. is described and Parayuanamia Xing & Li is considered a junior synonym of Yuanamia Zhang & Duan syn. n. Both genera are newly recorded from Thailand. A revised key to the Palearctic and Oriental genera of Deltocephalini is provided. PMID- 27394580 TI - Pamphilius ishikawai feeds on Astilbe: the first record of Pamphiliidae (Hymenoptera) associated with Saxifragaceae. AB - Based on field observations and rearing experiments in Nagano and Tochigi prefectures in central Honshu, Japan, host plants and life history of a leaf rolling sawfly, Pamphilius ishikawai Shinohara, 1979, are recorded for the first time. The larva is a solitary leaf-roller on Astilbe. This is the first record of the Saxifragaceae as a host plant of the Pamphiliidae. We made molecular phylogenetic analysis using mitochondrial cytochrome oxidase subunit 1 (COI) gene sequences for nine individuals of P. ishikawai feeding on three different species of Astilbe in two localities with different climates and for six outgroup pamphiliine species. It revealed very small genetic variability within P. ishikawai and suggested probable monophyly of the P. sulphureipes group. PMID- 27394581 TI - Notoraja martinezi sp. nov., a new species of deepwater skate and the first record of the genus Notoraja Ishiyama, 1958 (Rajiformes: Arhynchobatidae) from the eastern Pacific Ocean. AB - A new arhynchobatid skate, Notoraja martinezi, sp. nov., is described from four specimens collected from the eastern Central Pacific from Costa Rica to Ecuador and between depths of 1256-1472 m. The new species is placed in the genus Notoraja based on the long and flexible rostrum and its proportionally long tail with respect to total length. This species is distinct from its congeners in the Western Pacific by the straight margins of its rostrum, long anterior lobes of pelvic fins, and its abundant and very well developed caudal thorns. PMID- 27394582 TI - Revision of Physobates (Acari, Oribatida, Tegoribatidae) and redescription of Physobates spinipes Hammer, 1962 with comments on tegoribatid genera. AB - Herein we review the genus Physobates Hammer, 1962 and redescribe P. spinipes Hammer 1962 based on material collected in Buenos Aires, Argentina. After a morphological comparison among species of Tegoribatidae genera, we propose a new junior synonym, Paraphysobates Mahunka, 1985. A key to identify tegoribatid genera is also provided. PMID- 27394583 TI - First discovery of a new species of Newmanella Ross, 1969 (Balanomorpha: Tetraclitidae) in the western Pacific, with a note on the new status of Neonrosella Jones, 2010. AB - The present study describes a new species of Newmanella Ross, 1969 (Thoracica: Tetraclitidae: Newmanellinae) from Taiwan. Species in this genus are believed to be distributed in tropical western Atlantic waters and the present study is the first report of a new species of Newmanella in the western Pacific. Newmanella spinosus sp. nov. is morphologically close to N. radiata Bruguiere, 1789 but it is distinguished from N. radiata by the morphology of the scutum, tergum, cirrus II, mandible and maxillule. Sequence divergence of 12S rDNA between N. radiata and N. spinosus sp. nov. reached 7.6%, suggesting these are two different species. Newmanella spinosus sp. nov. is distributed in the Philippines, Taiwan and Okinawa but is absent from Hong Kong, Hainan and China. The distribution is probably affected by the Kuroshio Current. The subfamily Newmanellinae Ross and Perreault, 1999 contains two genera, Newmanella and Yamaguchiella Ross & Perreault, 1999. Neonrosella Jones, 2010 is a subgenus of Yamaguchiella. A recent molecular analysis (Tsang et al. 2015) determined that Yamaguchiella and Neonrosella are located in two distinct and distantly-related clades within the tetraclitid clade, suggesting that the subgenus Neonrosella is not closely related to Yamaguchiella and should be elevated to generic status. PMID- 27394584 TI - Caprellidae (Crustacea: Peracarida: Amphipoda) from the Red Sea and Suez Canal, with the redescription of Metaprotella africana and Paradeutella multispinosa. AB - The Caprellidae from the Red Sea are reviewed based on the literature data and new collections from the Hurghada coasts. So far, only six valid species has been reported from the Red Sea and Suez Canal: Caprella equilibra Say, 1818, Hemiaegina minuta Mayer, 1890, Metaprotella africana Mayer, 1903, Paracaprella pusilla Mayer, 1890 and Paradeutella multispinosa Schellenberg, 1928 and Pseudocaprellina pambanensis Sundara Raj, 1927. The type material of M. africana (deposited in the Museum nacional d'Histoire naturelle, Paris) and Paradeutella multispinosa (deposited in the Museum fur Naturkunde, Berlin) are redescribed and illustrated in detail. P. pambanensis and H. minuta were the most abundant species in the collections along the northern coast. Most of the sampling effort has been focused on algae from shallow waters; additional substrates such as sediments, hydroids and coral rubble, especially from areas deeper than 15 meters should be explored. The number of caprellid species in the Red Sea is low compared to adjacent waters, as the Mediterranean Sea. However, further research and more extensive caprellid collections should be conducted along the coasts of Saudi Arabia, Yemen, Sudan and Eritrea, which are still unexplored. PMID- 27394585 TI - A new cave species of the genus Protaphorura Absolon, 1901 (Collembola, Onychiuridae) from the Western Carpathians (Slovakia) with critical comments to the Palaearctic representatives of the genus. AB - The new species Protaphorura borinensis sp. nov. from a cave of the Western Carpathians, Central Europe, is described. It belongs to congeners with ~40 vesicles in PAO and three pseudocelli at the base of antennae and the hind margin of head. P. borinensis sp. nov. has coarse granulation of cuticle on head, and specific distribution of "s" chaetae on abdominal terga and chaetotaxy of ventral tube. Critical comments to the Palaearctic representatives of the genus Protaphorura and an identification key to 85 species are provided. PMID- 27394586 TI - Shallow-water reef ophiuroids (Echinodermata: Ophiuroidea) of Reunion (Mascarene Islands), with biogeographic considerations. AB - Despite their importance in marine biodiversity, invertebrates are far less studied than vertebrates. Given the current global biodiversity crisis and insufficient taxonomic resources, sustained efforts need to be undertaken to assess species diversity, especially in the highly threatened 'biodiversity hotspots'. Reunion is a young volcanic island lying in the Mascarene Islands (south-western Indian Ocean, SWIO), a marine biodiversity hotspot. A substantial sampling effort was conducted around Reunion Island to document shallow water reef-associated ophiuroid (brittle-stars) diversity, a class recognised as the most diverse among echinoderms. A total of 33 species were documented, increasing the known species richness of the island by 56%. Findings include 15 new records for Reunion, 11 for the Mascarene Islands and 8 for the Indian Ocean. The most diverse family was Ophiocomidae, a family of large, abundant and conspicuous tropical species. Even in this well studied family, a new species was revealed by this survey. Morphological variants together with DNA sequence variations within several species revealed cryptic species. We compared our results with the known fauna of other Mascarene Islands and discuss biogeographic implications for the region. PMID- 27394587 TI - New records of caridean shrimp (Crustacea: Decapoda) from hydrothermally influenced fields off Futuna Island, Southwest Pacific, with description of a new species assigned to the genus Alvinocaridinides Komai & Chan, 2010 (Alvinocarididae). AB - Five species of caridean shrimp, including four Alvinocarididae Christoffersen, 1986 and one thorid species of the genus Lebbeus White, 1847, are reported from the recently discovered hydrothermal vent field off Futuna Island in the Southwest Pacific (depths 1418-1478 m): Alvinocaridinides semidentatus n. sp., Alvinocaris komaii Zelnio & Hourdez, 2009, Nautilocaris saintlaurentae Komai & Segonzac, 2004, Rimicaris variabilis (Komai & Tsuchida, 2015), and Lebbeus wera Ahyong, 2009. The new species, provisionally assigned to Alvinocaridinides Komai & Chan, 2010, is readily distinguished from the type species of the genus, A. formosa Komai & Chan, 2010, by the characteristic armature of the rostrum and of the propodi of the third and fourth pereopods and the possession of ischial spines on the third and fourth pereopods. Identification of R. variabilis has been confirmed by morphology and sequence comparison of mitochondrial COI gene. The geographical range of L. wera is extended to the north from the Brothers Caldera in the Kermadec Ridge. PMID- 27394588 TI - Review of the harvestfishes, genus Peprilus (Perciformes: Stromateidae),
of the Atlantic coast of South America. AB - Currently, seven valid species are recognized in the genus Peprilus. Found from United States to Argentina, Peprilus paru has a complex nomenclatural history, with seven junior synonyms, three from North America and four from South America. As there has been no recent research, it remains unclear whether species representatives in the north-south axis represent different populations of a single species or distinct species. By comparison of type specimens as well as a comprehensive collection of non-type specimens, this paper aims to clarify the taxonomic status of the nominal species listed as junior synonyms of Peprilus paru in the Atlantic side of South America. Based on morphological data and DNA barcoding, Peprilus crenulatus Cuvier, 1829 and P. xanthurus (Quoy & Gaimard, 1825) are resurrected, while Rhombus argentipinnis Cuvier, 1833 and Rhombus orbicularis Guichenot, 1866, are considered to be junior synonyms of P. crenulatus. PMID- 27394589 TI - Revision of Cervonema Wieser, 1954 and Laimella Cobb, 1920 (Nematoda: Comesomatidae) with descriptions of two species from East Sea, Korea. AB - One new and one known species of the family Comesomatidae Filiepjev, 1918 were collected from marine sediments in the East Sea, Korea. Cervonema donghaensis sp. nov. is related to C. proximamphidum Tchesunov, 2000 and C. chilensis Chen & Vincx, 2000 but differs from them by the presence of the gubernaculum and by having outer labial setae and cephalic setae of unequal length. It differs from C. proximamphidum by having a rather shorter tail and the shape of the posterior widening of the pharynx, which has distinct muscular striation. Cervonema donghaensis sp. nov. differs from C. chilensis in body length, higher de Man's ratio c, and having a shorter cylindrical portion of the tail. Cervonema deltensis Hope & Zhang 1995 is considered as a junior synonym of C. tenuicauda (Schuurmans Stekhoven, 1950) Wieser, 1954. Specimens of Laimella filipjevi Jensen, 1979 from East Sea, Korea largely agree with the original description of Jensen (1979) of nematodes from the Western Baltic Sea, except for slight differences in length of cephalic setae and spicules. It also coincides well with the redescription of L. filipjevi by Tchesunov (2000) based on specimens from the White Sea. Pictorial keys for the identification of valid species in the genera Cervonema Wieser, 1954 and Laimella Cobb, 1920 are given. PMID- 27394590 TI - Euconnus octosetosus Franz transferred to Plaumanniola Costa Lima: implications for the systematics of Scydmaeninae (Coleoptera: Staphylinidae). AB - Euconnus octosetosus Franz (Brazil) is demonstrated to show diagnostic characters of the enigmatic genus Plaumanniola Costa Lima. Although this intriguing beetle is much more slender than previously known Plaumanniolini, it differs from Plaumanniola merely in the hypostomal ridges connected mesally and a loose structure of the antennal club. Euconnus octosetosus is transferred to Plaumanniola, resulting in P. octosetosa (Franz) comb. n. Comparative study shows gradual transformations of presumably defensive structural adaptations in Plaumanniola, suggesting evolution from a slender Euconnus-like ancestor to species with a strongly broadened body. Plaumanniola octosetosa is most slender of all species, with long and loosely assembled antennae and weakly flattened legs, whereas P. sanctaecatharinae Costa Lima and P. regina Jaloszynski show most derived characters; these beetles are morphologically adapted to curl in a ball. Plaumanniola simplicisima Jaloszynski represents an intermediary body form. Plaumanniolini Costa Lima is placed as a junior synonym of Glandulariini Schaufuss (= Cyrtoscydmini Schaufuss). A revised diagnosis of Plaumanniola and an overview of the current systematics of Scydmaeninae are given. PMID- 27394591 TI - Redescription of Paraleptophlebia falcula Traver 1934 with notes on status and composition of Paraleptophlebia Lestage 1917 and Neoleptophlebia Kluge 1997 (Ephemeroptera: Leptophlebiidae). AB - The taxon Paraleptophlebia Lestage 1917 is accepted here in generic rank, so rank of Neoleptophlebia Kluge 1997 is also raised from subgenus to genus, and the following new combinations are proposed: Neoleptophlebia adoptiva (McDunnough 1929) comb. n., N. assimilis (Banks 1914) comb. n., N. erratica (Kang & Yang 1994) comb. n., N. heteronea (McDunnough 1924) comb. n., N. japonica (Matsumura 1931) comb. n. (= Paraleptophlebia chocolata Imanishi 1937), N. mollis (Eaton 1871) comb. n., N. memorialis (Eaton 1884) comb. n., N. spina (Kang & Yang 1994) comb. n., N. swannanoa (Traver 1932) comb. n., N. temporalis (McDunnough 1926) comb. n., N. vladivostokica (Kluge 1982) comb. n. Larvae, male and female imagoes and eggs of Paraleptophlebia falcula Traver 1934 are described based on reared specimens from Siberia and Russian Far East; larvae and eggs are described for the first time. Characters of this species agree with diagnosis of Paraleptophlebia in the restricted sense; comparison of larva of P. falcula with other known larvae of Paraleptophlebia is given. Formerly this species was known as imagoes from limited area in Western Nearctic. According to the new data, it is widely distributed in northern part of Amphipacific Sector of Holarctic, and its area includes Polar Urals (Komi Republic), Siberia (Transbaikal Kray, Sakha Yakutia and Amurskaya Oblast' of Russia) and west of North America (Oregon, Idaho and Washington states of USA). PMID- 27394592 TI - A new genus of the tribe Pambolini (Hymenoptera: Braconidae: Exothecinae) from the Papua New Guinea with a key to the World genera. AB - A new distinctive genus Spathiophaenodus gen. nov. from the tribe Pambolini (Braconidae: Exothecinae), with type species Spathiophaenodus annae sp. nov. from Papua New Guinea, is described and illustrated. The original key to the World genera of the tribe Pambolini is provided. PMID- 27394593 TI - A new species of Enderleina Jewett (Plecoptera, Perlidae) from Amazonas State, Brazil. AB - Enderleina Jewett, 1960 is one of the least-known Perlidae genera in northern South America, including six species. During an aquatic insect survey of the northern portion of Amazonas State, Brazil, we collected a male Enderleina with a distinct pronotum pattern and genitalic morphology. The objectives of this study are to describe a new species of Enderleina based on male morphology. The new species can be distinguished from all other Enderleina species in the male by the presence of a paired thin dark band on the mesal region of pronotum and by the structure of the penial armature. PMID- 27394594 TI - An annotated checklist of Platypodinae and Scolytinae (Coleoptera: Curculionidae) from Iran. AB - We provide an annotated checklist of species of bark and ambrosia beetles (Curculionidae: Platypodinae and Scolytinae) recorded from Iran, with information on distribution, host trees, biology and taxonomy. Two species of Platypodinae and 79 species of Scolytinae are recorded. Hypothenemus crudiae (Panzer, 1791), Scolytus koenigi Schevyrew, 1890 and Xyleborus monographus Fabricius, 1792 are recorded for the first time from Iran. Previous records of three further species are considered dubious and require confirmation. PMID- 27394595 TI - Revision of Plumarius Philippi 1873 (Hymenoptera: Chrysidoidea, Plumariidae) from Argentina north of Patagonia, with description of eighteen new species. AB - Twenty six species of Plumarius from Argentina north of Patagonia are revised. Eighteen new species: Plumarius politus sp. nov., P. sarophorus sp. nov., P. globulosus sp. nov., P. angulatus sp. nov., P. noa sp. nov., P. divergens sp. nov., P. malaris sp. nov., P. gracilior sp. nov., P. riojanus sp. nov., P. exophthalmus sp. nov., P. planatus sp. nov., P. albinervis sp. nov., P. truncatus sp. nov., P. mikrommatus sp. nov., P. obscurus sp. nov., P. gracilis sp. nov., P. fidalgoi sp. nov., and P. ocellulatus sp. nov. are described and illustrated. A new record for known species as well as a key to 26 known species in the region is given. A redescription of P. tumidulus Papp, 2000, which is the first record of the family Plumariidae from Uruguay, is done. PMID- 27394596 TI - A review of the genus Kiwaia Philpott, 1930 (Lepidoptera, Gelechiidae) in the Palaearctic Region. AB - Fourteen Kiwaia-species are recorded from the Palaearctic Region. Eight new species are described from China: Kiwaia (Empista) mengdana sp. n. (Qinghai), Kiwaia (Empista) nyingchiensis sp. n. (Xizang), Kiwaia (Empista) septentrionala sp. n. (Ningxia, Gansu, Shanxi and Sichuan), Kiwaia (Empista) centrica sp. n. (Gansu, Hunan), Kiwaia (Empista) montana sp. n. (Xizang), Kiwaia (Empista) medogia sp. n. (Xizang), Kiwaia (Empista) yadongensis sp. n. (Xizang) and Kiwaia (Empista) povolnyi sp. n. (Xizang). The hitherto unknown female of Kiwaia (Empista) kostjuki is described and this species is recorded from China for the first time. Gelechia dryosyrta Meyrick, 1931 from India is trasferred to Kiwaia: K. (Empista) dryosyrta (Meyrick, 1931) comb. n. Redescriptions and identification keys for all the Palaearctic species are provided, accompanied by illustrations of the adults, and male and female genitalia. PMID- 27394597 TI - Reappraisal of the two axiid genera Manaxius Kensley, 2003 and Calaxidium Sakai, 2014, and description of a new species of Calaxius Sakai & de Saint Laurent, 1989 from French Polynesia, Southwest Pacific
(Crustacea: Decapoda: Axiidea). AB - Discovery of an undescribed species of axiid shrimp from French Polynesia, Southwest Pacific, led the author to assess the taxonomic status of the two nominal genera, Manaxius Kensley, 2003 and Calaxidium Sakai, 2014. As a result, these two genera are synonymized under Calaxius Sakai & de Saint Laurent, 1989, because there are no significant differences in generic characters among the three taxa. An emended generic diagnosis of Calaxius is presented. The new species, Calaxius poupini, is morphologically similar to C. euophthalmus (De Man, 1905), C. izuensis Komai, 2011, C. kensleyi Clark, Galil & Poore, 2007, C. mimasensis (Sakai, 1967), C. pailoloensis (Rathbun, 1906) and C. sibogae (De Man, 1925), but the poorly developed armature on the ventral margin of each cheliped merus distinguishes the new species from the other six allied species. Some points of taxonomic confusion relating to Calaxius are clarified. PMID- 27394598 TI - Validity of a blue stripe snapper, Lutjanus octolineatus (Cuvier 1828) and a related species, L. bengalensis (Bloch 1790) with a new species (Pisces; Lutjanidae) from the Arabian Sea. AB - Lutjanus octolineatus (Cuvier 1828), previously considered a junior synonym of Lutjanus bengalensis (Bloch 1790), is shown to be a valid species and lectotypes are designated. Both species are redescribed. The two species have overlapping distributions in the Indian Ocean, but are clearly separable by different dorsal fin spine counts, blue-striped pattern on the body and the presence or absence of a subocular extension of cheek scales. Lutjanus octovittata (Valenciennes 1830), formerly assigned to synonymy of L. bengalensis, is considered a junior synonym of L. octolineatus based on examination of the holotype. Lutjanus sapphirolineatus n. sp., a species formerly misidentified as L. bengalensis, is described based on 10 specimens from Oman and Somalia. The new species differs from the three species above by a combination of different characters. Analysis of the mitochondrial cytochrome c oxidase subunit 1 (CO1, 603 bp) genetic marker, also strongly supports the validity of each species of the blue-striped snapper complex as distinct. PMID- 27394599 TI - A study of the genus Protosticta Selys, 1855, with descriptions of four new species from Vietnam (Odonata: Platystictidae). AB - The genus Protosticta Selys, 1855 from Vietnam is revised. Four new species, P. ngoai spec. nov., P. socculus spec. nov., P. pseudocuriosa spec. nov., and P. spinosa spec. nov. are described; detailed morphological structures of four species P. beaumonti Wilson, 1997 (dark form), P. caroli van Tol, 2008, P. grandis Asahina, 1995, and P. satoi Asahina, 1997, are provided. P. beaumonti is newly recorded for Vietnam. The female of P. caroli is described for the first time. P. linnaei van Tol, 2008, is also listed here, based on the original description and visual inspection of the type specimens. The occurrence of P. khaosoidaoensis Asahina, 1984, in Vietnam is reviewed and rejected. A total of nine Protosticta species have now been recorded for Vietnam. PMID- 27394600 TI - Two new species of whip spider (Amblypygi): an epigean and a cave dwelling Charinus Simon, 1892 from Belize. AB - Central America is rich in whip spider species, mainly of the genera Phrynus and Paraphrynus (Phrynidae), but also includes few registers of Charinus (Charinidae) with no description of taxa. In this paper two new species of Charinus from Belize are described and illustrated (Charinus belizensis sp. nov. and Charinus reddelli sp. nov.) being the first species named from Central America. New records of Charinus victori Armas, 2010 from Puerto Rico, a comparative table listing the differential characters of the Caribbean and Central American species, and a distributional map of those species are also provided. PMID- 27394601 TI - Chaetotaxy of Neotropical Cyphoderus caetetus sp. nov. with comments on the taxonomic position of Cyphoderinae within Paronellidae (Collembola, Entomobryoidea). AB - The description of a new species, Cyphoderus caetetus sp. nov., led to comparisons among Paronellidae (Cyphoderinae and Paronellinae), which showed that the chaetotaxy of the first abdominal segment is very similar in Cyphoderus, Troglobius (Cyphoderinae) and Trogolaphysa (Paronellini), and much reduced in relation to that seen in Lepidonella (Paronellinae, Bromacanthini), Pseudosinella and Seira (Entomobryidae). This feature, along with the presence of pseudopores behind the posterior row of setae on the fourth abdominal segment as seen in Troglopedetes, Trogolaphysa and Cyphoderinae (absent in Lepidonella and Entomobryidae), suggests that Cyphoderinae is more closely related to tribe Paronellini than Paronellini is to Bromacanthini and Entomobryidae, and that the subfamily Paronellinae is paraphyletic if Cyphoderinae is excluded. We propose including Cyphoderini as the apical group in Paronellinae together with Paronellini (Trogolaphysa and Troglopedetes). PMID- 27394602 TI - A new species of Lamelligomphus Fraser, 1922 (Odonata: Gomphidae) from southern Yunnan, China. AB - Lamelligomphus annakarlorum sp. nov. is described based on specimens collected from southern Yunnan Province, China (holotype male: Xishuangbanna National Nature Reserve, 21 degrees 57'59''N, 101 degrees 12'37''E, Xishuangbanna Dai Autonomous Prefecture, Yunnan Province, China). All type specimens of the new species have been deposited in the Collection of Aquatic Animals, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan City, Hubei Province, China. It is compared with Lamelligomphus camelus (Martin, 1904), which shares some similar characters. PMID- 27394603 TI - Ethmolaimus riparius sp. n. and Paramononchus major sp. n. (Nematoda) from Lake Baikal, Russia. AB - Two new nematode species found in Lake Baikal (Russia) are described and illustrated. Ethmolaimus riparius sp. n. is morphologically close to E. pilosus Shoshin, 1998 and E. lanatus Shoshin, 1998. The new species differs from E. pilosus by the longer and thinner body (L = 1228-1501 um, a = 26-34 vs L = 720 1070 um, a = 19-23), larger stoma (26-32 um long vs 19-24 um long), longer spicules and gubernaculum (45-50 um long and 21-25 um long vs accordingly 32-37 um long and 8 um long). E. riparius sp. n. differs from E. lanatus by the longer body (L = 1228-1501 um vs L = 680-1180), shorter cephalic setae (its length is equal 1.1-1.4 labial region diameter vs 1.6-2.1 labial region diameter) and longer spicules and gubernaculum (45-50 um long and 21-25 um long vs accordingly 25-30 um long and 7-8 um long). Paramononchus major sp. n is close to P. orientalis Gagarin & Naumova, 2012, but differs from it by the longer body (L = 5926-7820 um vs L = 3081-3778 um), longer spicules (410-475 um long vs 208-238 um long) and larger number of precloacal supplements (52-61 vs 21-24). Keys for the identification of valid species of the genera Ethmolaimus and Paramononchus are given. PMID- 27394604 TI - Four new species of Pomphopsilla Jaloszynski and a new record of Cephennodes glabella Castellini in the Democratic Republic of the Congo
(Coleoptera: Staphylinidae: Scydmaeninae). AB - Four new species of the genus Pomphopsilla Jaloszynski are described, all based on specimens collected in the north-eastern part of DR Congo: P. pygmaea sp. n., P. pseudosoror sp. n., P. similis sp. n., and P. gumovskyi sp. n. Previously Pomphopsilla, represented by two species, was known to occur in Kenya; the only genera of Cephenniini recorded from DR Congo were Cephennodes Reitter and Cephennomicrus Reitter. Cephennodes (s. str.) glabella Castellini, so far known only from the type series, is recorded from the same region of Congo, based on numerous specimens collected by yellow pan traps. Because figures in the original description of this species were relatively schematic, the aedeagus and modifications of the head in the male are illustrated. PMID- 27394605 TI - Dendropaemon Perty, 1830: taxonomy, systematics and phylogeny of the morphologically most derived phanaeine genus (Coleoptera: Scarabaeidae, Scarabaeinae, Phanaeini). AB - The taxonomy and systematics of the Neotropical genus Dendropaemon Perty is revised. The current study recognize 41 species organized into 12 subgenera. The establishment of the subgenera is reflecting the presented phylogenetic analysis. Six subgenera are established from previously available genus group names: Coprophanaeoides Edmonds, 1972; Dendropaemon Perty, 1830; Enicotarsus Laporte, 1831; Eurypodea Klages, 1906; Onthoecus Lacordaire, 1856; Paradendropaemon Edmonds, 1972 and Tetramereia Klages, 1907. Six additional subgenera are described as new: Glaphyropaemon n. subg.; Nigropaemon n. subg.; Rutilopaemon n. subg.; Streblopaemon n. subg.; Sulcopaemon n. subg. and Titthopaemon n. subg. The following 18 species are described as new: Dendropaemon (Coprophanaeoides) bluti n. sp.; Dendropaemon (Coprophanaeoides) carinifer n. sp.; Dendropaemon (Coprophanaeoides) compressipennis n. sp.; Dendropaemon (Coprophanaeoides) cribrosus n. sp.; Dendropaemon (Coprophanaeoides) furtadoi n. sp.; Dendropaemon (Coprophanaeoides) inflatus n. sp.; Dendropaemon (Coprophanaeoides) pilosissimus n. sp.; Dendropaemon (Dendropaemon) aenigmaticus n. sp.; Dendropaemon (Dendropaemon) amazonicus n. sp.; Dendropaemon (Dendropaemon) angustulus n. sp.; Dendropaemon (Dendropaemon) flechtmanni n. sp.; Dendropaemon (Dendropaemon) larseni n. sp.; Dendropaemon (Glaphyropaemon) inemarginatus n. sp.; Dendropaemon (Nigropaemon) nigritulus n. sp.; Dendropaemon (Onthoecus) lydiae n. sp.; Dendropaemon (Onthoecus) morettoi n. sp.; Dendropaemon (Paradendropaemon) vazdemelloi n. sp.; Dendropaemon (Sulcopaemon) latistriatus n. sp.. The following nomen novum: Dendropaemon (Onthoecus) attalus nom. nov. is created to replace the primary junior homonym Dendropaemon amyntas Harold, 1868. Except for Dendropaemon montei Pessoa & Lane, 1936, type material of all the species have been examined and lectotypes designated for the following two species: Dendropaemon fasces Blut, 1939 and Dendropaemon lobatus Waterhouse, 1891. In order to stabilize nomenclature, neotypes were also designated for the following species: Dendropaemon convexus Harold, 1869; Enicotarsus ater Laporte, 1832; Enicotarsus quadratus Laporte, 1932 and; Enicotarsus viridipennis Laporte, 1831. Color habitus are presented for each of the valid species. PMID- 27394606 TI - Taxonomic review of the Neotropical genus Gephyrocharax Eigenmann, 1912 (Characiformes, Characidae, Stevardiinae). AB - Gephyrocharax currently comprises 13 valid species distributed in the Cis- and Trans-Andean basins of the Neotropical region. The genus has not been reviewed in more than 80 years, and thus, the older species descriptions are poorly detailed, based on small samples of specimens, and supported by uninformative diagnoses. The present review is based on external morphology and morphometric, meristic, osteological, and myological data. Counts and measurements were analyzed using bivariate and multivariate statistical procedures implemented in PAST and SigmaPlot. Cases of synonyms and geographic variation were evaluated using sheared principal components analyses (SPCA). Eleven valid species are recognized for the genus: G. atracaudatus, G. caucanus, G. chocoensis, G. intermedius, G. major, G. martae, G. melanocheir, G. sinuensis, G. torresi, G. valencia, and G. venezuelae. Gephyrocharax whaleri is proposed as junior synonym of G. intermedius, and Corynopomops opisthopterus and G. chaparae are proposed as junior synonyms of G. major. A lectotype for G. major and neotypes for G. melanocheir and G. sinuensis are designated. Gephyrocharax atracaudatus is confirmed for the first time in the Palenque River basin of the Pears islands in the Gulf of Panama. New distributional records are reported for G. major in the Amazon River basin. Gephyrocharax major and G. valencia are the most widely distributed members of the genus. Distributional and georeferenced maps are presented for all Gephyrocharax species based on extensive examined material. An identification key of the Gephyrocharax species is provided. PMID- 27394607 TI - Revision of the subgenus Aleochara Gravenhorst of the parasitoid rove beetle genus Aleochara Gravenhorst of Japan (Coleoptera: Staphylinidae: Aleocharinae). AB - The Japanese members of the subgenus Aleochara Gravenhorst, 1802 of the genus Aleochara Gravenhorst, 1802 are revised. Six species are recognized: Aleochara (Aleochara) coreana Bernhauer, 1926; A. (A.) curtula (Goeze, 1777); A. (A.) lata Gravenhorst, 1802; A. (A.) parens Sharp, 1874; A. (A.) postica Walker, 1858 [= A. (A.) clavigera Sharp, 1874, n. syn.; A. (A.) nitouensis Bernhauer, 1935, n. syn.; A. (A.) marginicollis Cameron, 1942, n. syn.], and; A. (A.) yaeyamensis n. sp. (Yaeyama Islands, the Ryukyus). We recognize A. niponensis Sharp, 1888, sp. rev., currently synonymized under A. clavigera, as a valid species and transfer it to the subgenus Xenochara Mulsant & Rey, 1874. "A. (A.)" kochi Bernhauer, 1941 [="A. (A.)" globus Pace, 1999, n. syn.] is excluded from Aleochara and re-assigned instead to Paraleochara Cameron, 1920. Paraleochara is new to the Palearctic region, and Paraleochara kochi (Bernhauer, 1941), n. comb. represents the second species of the genus. Lectotypes of A. niponensis, A. parens, and A.discoidea are designated. All species are described, keyed, and figured, with habitus photographs. Line drawings of the adult mouth parts of A. (A.) curtula (Goeze, 1777) are shown. The diversity, distribution, and phylogenetic relationships of the subgenus in Japan are also discussed. PMID- 27394608 TI - The Australian Monstrilloida (Crustacea: Copepoda) II. Cymbasoma Thompson, 1888. AB - Monstrilloid copepods collected during the past two decades from zooplankton surveys in reef and coastal areas of Australia were analyzed. A first contribution included the taxonomic analysis of three genera of the Monstrilloida, Monstrillopsis Sars, 1921, Maemonstrilla Grygier & Ohtsuka, 2008, and the newly described Australomonstrillopsis Suarez-Morales & McKinnon, 2014. In this document a taxonomic analysis of the species belonging to the genus Cymbasoma Thompson, 1888 is provided. A total of 28 species were found, most of them being undescribed. Seventeen species were described based on females only and eight on male specimens while three species were described from both sexes. Males of Australian species of Cymbasoma are distinguished by details of the genital complex, body size and proportions, ornamentation and processes of the cephalic region, number of caudal setae, and the characteristic structure or ornamentation of the genital lappets. Two main groups of males were distinguished on the basis of the number of caudal setae (3 or 4). As for the females, 20 of the 25 new species of Cymbasoma have fifth legs with an unarmed inner lobe and three setae on the outer lobe; one of these species (C. jinigudira sp. nov.) belongs to the C. longispinosum species-group (sensu Ustun et al. 2014). Another group, consisting of five species, has only two setae on the outer (exopodal) lobe. There were no Australian species of Cymbasoma with a single lobe. A species group, named after C. agoense, is proposed to include species sharing a globose body and a female fifth leg with a large endopodal lobe and an outer (exopodal) lobe with two setae. The females of the new species of Cymbasoma from Australia can be distinguished from their known congeners by unique combinations of characters including the type of body ornamentation, body size and shape, antennule armature and proportions, the presence of distinctive features of the legs 1-4, the presence/absence of processes on the genital compound somite, and the presence/absence of a constriction of the anal somite. We report the occurrence of two previously described species, C. agoense Sekiguchi, 1982 from Japan and C. bali Desai & Krishnaswamy, 1962 from India in Australian waters. Considering the addition of the 25 new species here described, the number of nominal species of the genus is now 66. A key to the Australian species of Cymbasoma (males and females) and a map showing their occurrence in Australia are also provided. PMID- 27394609 TI - Revision of fossil Metretopodidae (Insecta: Ephemeroptera) in Baltic amber-Part 3: Description of two new species of Siphloplecton Clemens, 1915, with notes on the re-discovered lectotype of Siphloplecton macrops (Pictet-Baraban & Hagen, 1856). AB - In this contribution, we provide a complementary description of the re-discovered lectotype of Siphloplecton macrops (Pictet-Baraban & Hagen, 1856). Additionally, complementary descriptions of S. barabani Staniczek & Godunko, 2012 and S. picteti Staniczek & Godunko, 2012 based on new material are given. Two new species, S. sartorii sp. nov. and S. gattolliati sp. nov., are described from male imagines and attributed to two newly defined species groups within Siphloplecton. PMID- 27394610 TI - Two new species and a new record of Bactrocera Macquart (Diptera: Tephritidae: Dacinae: Dacini) from India. AB - Two new species of Bactrocera Macquart, namely Bactrocera (Calodacus) harrietensis Ramani & David, sp. nov. and Bactrocera (Calodacus) chettalli David & Ranganath, sp. nov., are described from the Andaman and Nicobar Islands and Karnataka, India, respectively. Bactrocera (Zeugodacus) semongokensis Drew & Romig is recorded for the first time from India. PMID- 27394611 TI - Asiagomphus reinhardti sp. nov. (Odonata, Gomphidae) from eastern Cambodia and southern Laos. AB - Asiagomphus reinhardti sp. nov. is described by two males from Annamense Mountains in eastern Cambodia (holotype: Cambodia, Mondulkiri Province, the left tributary of the main river downstream from Buu Sraa Waterfall, 12 degrees 34'01 19'' N 107 degrees 24'50''-25'03'' E, ca 450 m a.s.l., 15 vi 2014, RMNH) and southern Laos. The species is characterised by a large caudal lobe on S10 in males and a blunt medial lateroventral projection at cercus. PMID- 27394612 TI - A New Crayfish of the Genus Cambarus (Decapoda: Cambaridae) From the Flint River Drainage in Northern Alabama and South Central Tennessee, U.S.A. AB - Examination of specimens of the crayfish species Cambarus (Hiaticambarus) longirostris and two recently described crayfish revealed the existence of an undescribed species from the Flint River watershed in northern Alabama and southern Tennessee. Cambarus (Hiaticambarus) lentiginosus differs from C. longirostris, C. (Hiaticambarus) andersoni, and C. (Hiaticambarus) diupalma in aspects of carapace and chela morphology and pigmentation pattern. Cambarus (H.) lentiginosus possesses a median carina on the dorsal surface of the acumen of the rostrum, a distinctly enlarged tubercle near the base of the opposable surface of the dactyl, and a speckled pigmentation pattern over a light base color; these characters are lacking in other known Hiaticambarus species. The known range of the species is restricted to the Flint River watershed. Cambarus (H.) lentiginosus is considered Endangered using American Fisheries Society conservation categorization. PMID- 27394613 TI - Descriptions of the immature stages and new host plant records of Notozulia entreriana (Berg) (Hemiptera: Cercopidae) pests of grasses in subtropical areas of the Americas. AB - Notozulia entreriana (Berg) (Hemiptera: Cercopidae) is one of the most common spittlebugs inhabiting the subtropical region of the America, inflicting important economic damage to grass crops. The immature stages are described and illustrated; the main characteristics that distinguish instars are the body size, color, number of flagellomeres, and number of tibial and metatarsomere spines. A key for identification of nymphs is provided as a tool to develop field studies. Nine host plants, all belonging to Poaceae, are recorded as breeding and feeding host plants from different localities in northern Argentina. PMID- 27394614 TI - Gordius gonzalezi, a new species of horsehair worms (Nematomorpha) from Spain. AB - A new species, Gordius gonzalezi, is described from the Iberian Peninsula, from the Sierra de los Tormantos in Central Spain. Characteristic for the species is the presence of multiple short spines on the cuticle, not present in this form in any other Gordius species. Additionally, two further specimens are reported, which could not be determined to species level. One male of the genus Gordius is close to G. aquaticus and one female with regular areoles could belong either to the genus Gordius or to Gordionus. PMID- 27394615 TI - A new species of the genus Eurhadina Haupt (Hemiptera: Auchenorrhyncha: Cicadellidae: Typhlocybinae) from Korea, with a key to Korean species. AB - The leafhopper genus Eurhadina Haupt, 1929 belongs to the tribe Typhlocybini of subfamily Typhlocybinae (Hemiptera: Auchenorrhyncha: Cicadellidae). Currently, genus Eurhadina includes 3 subgenera, Eurhadina Haupt 1929, Singhardina Mahmood 1967, Zhihadina Yang & Li 1991. A total of 20 valid species of subgenus Eurhadina have been described in the Nearctic and Palaearctic region and the subgenus Singhardina includes 57 species in the Oriental and Palaearctic region (Huang & Zhang 1999, Dworakowska 2002). The subgenus Zhihadina includes only 1 species from China (Yang & Lee, 1991). So far, four species of subgenus Eurhadina were recorded in the Korean Peninsula (Kwon & Huh 2001): Eurhadina (Eurhadina) betularia Anufriev, 1969, E. (E.) koreana Dworakowska, 1971, E. (E.) pulchella (Fallen, 1806), and E. (E.) wagneri Dworakowska, 1969. The majority of species belonging to the subgenus Eurhadina are difficult to distinguish by external appearance because the color patterns of the forewings are very similar among species. PMID- 27394616 TI - Diplosmittia caribensis, a new Orthocladiinae (Diptera: Chironomidae) from the Dominican Republic. AB - The genus Diplosmittia was erected by Saether (1981) based on Diplosmittia harrisoni from St. Lucia and St. Vincent in the British West Indies. Prior to the present study the genus comprised nine species, all except D. carinata Saether were known only from Neotropical Region (Ashe & O'Connor, 2012). During sampling in the surroundings of a highly organic polluted river, in the National Botanical Garden in Santo Domingo, Dominican Republic, the present second author collected several imagines of Diplosmittia that did not fit any taxon treated in the recent review of the genus (Pinho et al. 2009). In the present paper, the male of this new species is described and illustrated. PMID- 27394617 TI - First record of Calycina Blair, 1922 (Coleoptera, Mordellidae) in the Russian Far East with description of a new species. AB - The genus Calycina Blair, 1922 (Mordellinae, Mordellini) is one of the most fascinating and enigmatic genera of Mordellidae. The genus exhibits a pantropical distribution: one species with two subspecies in South America (Horak 1999; Leblanc 2013), one species in Africa (Horak 1999), three species in Southeast Asia (Horak 1999) and two species in the Papuan Region (Horak 1999; Ruzzier 2013). All species are known from only a few specimens, almost exclusively females, and appear to be generally very rare. Only Calycina major Nomura, 1967 and Calycina nigroapicalis Nomura, 1967 reach the Palearctic Region (Horak 2008; Ruzzier 2013) and no other species have been recorded from higher latitudes. The opportunity to study specimens from the Primorye region (Russian Far East) allowed the authors to identify a new species that is described below. PMID- 27394618 TI - Two new species of the genera Cidariplura Butler, 1879 and Oxaenanus Swinhoe, 1900 from Yunnan, China (Lepidoptera, Erebidae, Herminiinae). AB - The Herminiinae genus Cidariplura Butler, 1879 is distributed mainly in the Oriental and partially in the Palaearctic regions (Wu & Owada 2013). The characteristic features of the genus are the structure of the labial palpus, and male foretibia without sheath covering tarsus and containing a tuft of long hairs. PMID- 27394619 TI - A new species of the spider genus Taranucnus from Ukraine (Araneae, Linyphiidae). AB - Currently the linyphiid genus Taranucnus includes four species: T. setosus (O. P. Cambridge, 1863), the type species with Palearctic distribution, T. bihari Fage, 1931 (Eastern Europe), T. nishikii Yaginuma, 1972 (Japan) and T. ornithes (Barrows, 1940)(USA). In Ukraine Taranucnus is represented by two species, T. setosus and T. bihari. A detailed study of the male mentioned earlier as Taranucnus sp. (Chumak, Prokopenko & Tymochko 2007; Prokopenko, Chumak 2007), and several females close to T. bihari Fage, 1931 revealed a new species of this genus. Since it is hard to clarify the position of some of these females we report them below as T. cf. bihari. PMID- 27394620 TI - Review of the family Proctorenyxidae (Hymenoptera: Proctotrupoidea), with description of new species from South Korea. AB - Kozlov (1994) established a new parasitic proctotrupoid family, Renyxidae, for a single species, Renyxa incredibilis, from Primorskij Krai, in the Russian Far East. A new genus and species, Hsiufuropronia chaoi, was described from China, Beijing (Yang 1997) in the family Roproniidae. Lelej and Kozlov (1999) noticed that Renyxa was preoccupied and was initially used by Kurochkin and Slankis (1973) for a genus of flatworms (Cestoda: Litobothridae). According to Articles 39, 60 of the Code (ICZN 1999), the names of the genus and family were changed to Proctorenyxa Lelej & Kozlov, 1999 (Lelej & Kozlov 1999). He et al. (2002) transferred Hsiufuropronia from Roproniidae to Proctorenyxidae based on Yang's original description and illustrations, and synonymized Hsiufuropronia Yang under Proctorenyxa Lelej & Kozlov. Later, He and Xu (2015) proposed that the family name Proctorenyxidae should be replaced by Hsiufuroproniidae and the genera Proctonenyxa Lelej & Kozlov and Hsiufuropronia Yang should be separate. However, the replacement name Hsiufuroproniidae contradicts article 39 of the Code (ICZN 1999). PMID- 27394621 TI - Aphelochaeta (Polychaeta: Cirratulidae) from the Pacific coast of Costa Rica, with a description of five new species. AB - Five new species of bitentaculate Cirratulidae belonging to the genus Aphelochaeta are herein described from the Pacific coast of Costa Rica, all from shallow subtidal depths. Aphelochaeta antelonga sp. nov. is characterized by a long biannulate peristomium and fibrillated capillary setae and is from 11-18 m in the Gulf of Nicoya. Aphelochaeta guimondi sp. nov., with a wide dorsal trough in the thorax and hirsute capillaries (visible using SEM), is described from 11 26 m in the Gulf of Nicoya. Aphelochaeta praeacuta sp. nov., with its first peristomial annulation extending as a dorsal crest over the second annulation and first setiger, was collected from 11-28 m in Bahia Culebra. Aphelochaeta striata sp. nov., collected from 11-28 m in the Gulf of Nicoya, is recognized by its narrow body and the transverse blue stripes across the venter of setigers 5-8 produced with methyl green stain. Aphelochaeta zebra sp. nov., collected from a coral reef in Golfo Dulce, is characterized by its expanded posterior end and the darkly staining intersegmental regions using methyl green stain. Additionally, A. glandaria Blake, 1996, a species reportedly with a widespread geographic distribution (Blake, 1996), was also encountered subtidally from the Gulf of Nicoya and Golfo Dulce. PMID- 27394622 TI - Taxonomic notes on the genus Auranus (Opiliones, Laniatores, Stygnidae), with description of two new species. AB - Among the Amazonian families of harvestmen the members of Stygnidae are better known due to the recent revision of the family and efforts of specialists describing new taxa in the last few years. Species of Amazonian genus Auranus Mello-Leitao, 1941, have been collected in several inventories that were carried out in different locations of the Amazon basin. In this paper we provide a new diagnosis for Auranus, and the description of two new species: Auranus leonidas sp. nov. and Auranus xerxes sp. nov. from the Brazilian states of Roraima and Amazonas, respectively. We also offer complementary genital descriptions of Auranus hehu Pinto-da-Rocha & Tourinho 2012, Auranus parvus Mello-Leitao, 1941, and Auranus tepui Pinto-da-Rocha & Tourinho 2012. Five species are recognized in Auranus, including the two new species described in this paper. The lamina parva modified into a calyx is proposed as putative synapomorphy for the genus Auranus. Therefore, A. hoeferscovitorum, which does not possess this character, is removed from Auranus. Instead we propose for it the new combination Verrucastygnus hoeferscovitorum comb. nov. We also provide a key to the males of Auranus, and a map with the distribution for all species examined in this work. PMID- 27394623 TI - Chaunax multilepis sp. nov., a new species of Chaunax (Lophiiformes: Chaunacidae) from the northern Indian Ocean. AB - A new species of Chaunax is described on the basis of eight type and five non type specimens. This species belongs to the Chaunax abei species group and can be distinguished from congeners in the group by having a continuous tooth patch on the vomer, not divided into two patches, and four or five neuromasts in the lower preopercular series. It can be further separated by the following combination of characters: large green spots on dorsal surface; simple spinules on dorsal surface; 12 pectoral-fin rays; 13-16 neuromasts in pectoral series; 30-37 neuromasts in lateral-line proper; typically four neuromasts on caudal-fin base; typically 7 neuromasts in mandible; typically 12 gill rakers on second gill arch; gill chamber and buccal cavity pale; and peritoneum black. PMID- 27394624 TI - The phylogenetic relationships of a new Stream Toad of the genus Ansonia Stoliczka, 1870 (Anura: Bufonidae) from a montane region in Peninsular Malaysia. AB - Twelve species of Ansonia occur on the Thai-Malay peninsula, of which, five from Peninsular Malaysia, form a monophyletic group. One of these, A. jeetsukumarani, is endemic to the Titiwangsa Mountain Range, in which, we discovered a new population of Ansonia that is not A. jeetsukumarani or even its closest relative. Based on morphology, color pattern, and molecular phylogenetic analyses using the mitochondrial genes 12s and 16s rRNA, we have determined that this new species, A. smeagol sp. nov., forms the sister lineage to an upland, monophyletic group composed of A. jeetsukumarani, A. lumut, A. malayana, and A. penangensis. We have noted similar biogeographic patterns in other taxa from the Titiwangsa Mountain Range in a number of upland lineages in Peninsular Malaysia. We hypothesize that the phylogeographic structure of these upland populations is a result of stochastic processes stemming from interaction of climate-driven forest dynamics and life histories. PMID- 27394625 TI - Two new species of Cyphocharax (Teleostei: Characiformes: Curimatidae) from headwaters of the Jequitinhonha and Sao Francisco river basins, Minas Gerais, Brazil. AB - Two new species of Cyphocharax from southeastern Brazil are described. Both new species share with C. punctatus, and C. vanderi the presence of a midlateral series of irregular patches of dark pigmentation along the lateral line. Cyphocharax jagunco, new species, from Rio Jequitinhonha basin, is distinguished from C. lundi, C. punctatus, and C. vanderi by the number of patches of dark pigmentation along lateral line; the number of pored scales posterior to the hypural joint; the number of scales in the lateral line; and the number of scales rows above lateral line. Cyphocharax lundi, new species, from Rio Sao Francisco basin, is distinguished from C. jagunco, C. punctatus, and C. vanderi by the presence of dark spots above the lateral line; and the number of scales in the lateral line. Comments on the relationships of the new species within Cyphocharax are presented. PMID- 27394626 TI - A new species of Rhadinella (Serpentes: Colubridae) from the Sierra Madre del Sur of Guerrero, Mexico. AB - We describe a new species of Rhadinella from the Sierra Madre del Sur of Guerrero, Mexico, a region where the genus was previously unknown. This diminutive species is a member of a group of snakes previously allocated in the Rhadinaea godmani group, and more recently transferred to the genus Rhadinella. These snakes may have conspicuous dark longitudinal striping on a pale brown to orange background or may have dark brown to blackish dorsal ground coloration, which mostly or completely obfuscates a pattern of longitudinal striping. The new species is mostly dark with barely discernible slightly paler or darker striping (depending on how striping is interpreted). The closest relative of the new species, on the basis of morphological similarities and biogeography, appears to be Rhadinella donaji which occurs to the east in the Sierra Madre del Sur of Oaxaca about 275 km from the type-locality of the new species. PMID- 27394627 TI - Tupiperla (Plecoptera: Gripopterygidae) from southwestern Minas Gerais State, Brazil, with the description of Tupiperla amorimi n.sp. AB - The genus Tupiperla Froehlich 1969 occurs in Brazil from Bahia and Goias states south to Santa Catarina State and also in nearby areas of Misiones Province, Argentina and southern Paraguay. Recently, Duarte et al. (2014a, 2014b) described two new species from Bahia State. With the present new species, the number of known species of this genus is currently 19. PMID- 27394628 TI - Dryops renateae Gren & Przewozny sp. n. from Tajikistan (Coleoptera: Dryopidae). AB - The genus Dryops Olivier, 1791 has a worldwide distribution. In the Palaearctic region, it contains 34 species, from Tajikistan only one was recorded so far Dryops rufipes Krynicki, 1832 (Olmi 1976, Kodada & Jach 2006). During an expedition of last two authors to the Tajikistan in 2014 a series of new species was found, which is described in this paper. PMID- 27394629 TI - A new species Spilarctia duda (Lepidoptera: Erebidae, Arctiinae) from China. AB - A new tiger moth, Spilarctia duda sp. n., from southeast China, Sichuan is described. A diagnostic comparison with Spilarctia bipunctata Daniel, 1943 and Spilarctia clava (Wileman, 1910) is provided. During recent years the Chinese Arctiini have been intensively collected and explored (Fang, 2000; Dubatolov, 2010; Kishida, 2015; and numerous other publications), so the discovery of a distinctive new species near Maoxian, North part of Sichuan Province, was most unexpected. PMID- 27394630 TI - A new jumping spider of the genus Stenaelurillus Simon, 1886 from India (Araneae: Salticidae: Aelurillina). AB - The genus Stenaelurillus Simon, 1886 is known from 35 species worldwide, including 27 species from Africa and eight from Asia (four species known from India, one from Iran, one from China, one from Tibet and one from Vietnam) (World Spider Catalog 2016). The four species known from India are S. albus Sebastian et al., 2015, S. jagannathae Das, Malik & Vidhel, 2015, S. lesserti Reimoser, 1934 and S. sarojinae Caleb & Mathai, 2014 (Proszynski 2015; World Spider Catalog 2016). The present paper contains description of Stenaelurillus metallicus sp. nov., discovered from scrub jungle remnants of tropical dry evergreen forests, a unique habitat found in Madras Christian College campus, Chennai, Tamil Nadu, India. PMID- 27394631 TI - Two new synanthropic species of Anyphaena Sundevall (Araneae: Anyphaenidae) associated to houses in Mexico City. AB - The family Anyphaenidae is composed by 56 genera and 542 species worldwide (World Spider Catalog 2015). These spiders, known as "ghost spiders", are wandering hunters living in a variety of environments, from forests to deserts, and can be quite abundant in different crops such as cotton, sorghum and rice (Brescovit 1996; Young & Edwards 1990; Taylor & Pfannenstiel 2008). They typically live on vegetation, among dead leaves or under loose bark and rocks (Richman & Ubick 2005) but synanthropic associations have been reported for a few species (Jimenez 1998; Guarisco 1999; Duran-Barron et al. 2009). The genus Anyphaena has 81 species widely distributed in Asia, Central Europe, North America and Mexico (Brescovit 1996; Richman & Ubick 2005; World Spider Catalog 2015). The species from Noth America and Mexico were revised by Platnick (1974) who recognized four species groups (accentuata, celer, pectorosa and pacifica). Platnick (1977), Platnick & Lau (1975) and Brescovit & Lise (1989) complemented the revision of the genus in Central America. Presently, there are 27 species of Anyphaena recorded in Mexico (World Spider Catalog 2015), 24 of them from the celer group. Here, two new species of Anyphaena are described based in material collected during an inventory of spiders associated to houses in Mexico City, carried out by Duran-Barron et al. (2009). Both species have the diagnostic characters of the members of the pacifica group as defined by Platnick (1974), such as the lack of leg coxal spurs and the presence of a lightly sclerotized atrium in the female epigynum. These species represent the first record of the pacifica group in Mexico. The occurrence of Anyphaenidae associated to houses was reported in Mexico by Duran-Barron et al. (2009), who recorded Anyphaena obregon Platnick & Lau, 1975 and Hibana futilis (Banks, 1898) as frequent inhabitants inside houses. The species herein described are reported solely from urban areas and can be also characterized as frequent in these anthropic environments. PMID- 27394632 TI - A new species of Indo-Pacific Modulidae (Mollusca: Caenogastropoda). AB - Modulidae is a littoral cerithioid family exclusively encountered in tropical and subtropical regions. It contains 12 to 15 living species (some species are not clearly delimited). Only one species is known to occur in the vast Indo-Pacific region (Bouchet 2015) and two species in the eastern Atlantic. By comparison, the tropical American regions are relatively rich with at least eleven living species (two or three species in the eastern Pacific and nine or more in the western Atlantic), and an equivalent number or more of fossil species (Landau et al. 2014). PMID- 27394633 TI - Association between hypoalbuminemia and surgical site infection in vulvar cancers. AB - OBJECTIVE: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer. METHODS: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01). CONCLUSIONS: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication. PMID- 27394634 TI - Ecological status and sources of anthropogenic contaminants in mangroves of the Wouri River Estuary (Cameroon). AB - Mangroves are critically threatened by human activities, despite the important ecosystem functions and services they provide. Mangroves in Cameroon represent no exception to the worldwide trend of mangrove destruction, especially around Douala, on the Wouri river estuary. In two sites around Douala, we assessed the presence of sterols, PAHs, PCBs, DEHP, DDT and its metabolite p,p'-DDE and potentially toxic metals in sediment samples. As a proxy of ecological quality, we measured the diversity and abundance of macrobenthos assemblages. We detected p,p'-DDE contamination, with concentrations higher than 3MUgkg(-1) in 16 out of 26 samples which were attributed to recent widespread use of DDT. The detection of sterols revealed faecal contamination. Significant sensitivity of the macrobenthos to contaminants was revealed, with possible implications on the overall mangrove vulnerability to climate change and on the provision of ecosystem services to local populations. PMID- 27394635 TI - Damage and recovery assessment of the Philippines' mangroves following Super Typhoon Haiyan. AB - We quantified mangrove disturbance resulting from Super Typhoon Haiyan using a remote sensing approach. Mangrove areas were mapped prior to Haiyan using 30m Landsat imagery and a supervised decision-tree classification. A time sequence of 250m eMODIS data was used to monitor mangrove condition prior to, and following, Haiyan. Based on differences in eMODIS NDVI observations before and after the storm, we classified mangrove into three damage level categories: minimal, moderate, or severe. Mangrove damage in terms of extent and severity was greatest where Haiyan first made landfall on Eastern Samar and Western Samar provinces and lessened westward corresponding with decreasing storm intensity as Haiyan tracked from east to west across the Visayas region of the Philippines. However, within 18months following Haiyan, mangrove areas classified as severely, moderately, and minimally damaged decreased by 90%, 81%, and 57%, respectively, indicating mangroves resilience to powerful typhoons. PMID- 27394636 TI - Distribution of trace metals in surface seawater and zooplankton of the Bay of Bengal, off Rushikulya estuary, East Coast of India. AB - Concentrations of trace metals such as iron (Fe), copper (Cu), zinc (Zn), cobalt (Co), nickel (Ni), manganese (Mn), lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), vanadium (V), and selenium (Se) were determined in seawater and zooplankton from the surface waters off Rushikulya estuary, north-western Bay of Bengal. During the study period, the concentration of trace metals in seawater and zooplankton showed significant spatio-temporal variation. Cu and Co levels in seawater mostly remained non-detectable. Other elements were found at higher concentrations and exhibited marked variations. The rank order distribution of trace metals in terms of their average concentration in seawater was observed as Fe>Ni>Mn>Pb>As>Zn>Cr>V>Se>Cd while in zooplankton it was Fe>Mn>Cd>As>Pb>Ni>Cr>Zn>V>Se. The bioaccumulation factor (BAF) of Fe was highest followed by Zn and the lowest value was observed with Ni. Results of correlation analysis discerned positive affinity and good relationship among the majority of the trace metals, both in seawater and zooplankton suggesting their strong affinity and coexistence. PMID- 27394637 TI - Antimicrobial susceptibility patterns of community- and hospital-acquired methicillin-resistant Staphylococcus aureus from United States Hospitals: results from the AWARE Ceftaroline Surveillance Program (2012-2014). AB - Among 8437 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 143 medical centers in the United States (2012-2014), 7116 and 1321 were reported as community-acquired (CA) and hospital-acquired (HA) MRSA, respectively. CA-/HA-MRSA were most often isolated from patients with skin and skin structure infections (SSSI; 68.4/26.9%), pneumonia (13.7/49.0%) and bacteremia (10.0/17.7%). Overall, susceptibility rates were generally lower among HA-MRSA compared to CA-MRSA strains, especially for clindamycin (44.6 vs. 66.1%) and levofloxacin (21.4 vs. 35.5%). Also, susceptibility rates were lower for these two compounds among isolates from pneumonia compared to SSSI and bacteremia. Ceftaroline was broadly active against 98.0% of CA-MRSA and 94.3% of HA-MRSA (MIC50/90, 1MUg/mL for both; no resistant isolate) overall, with little variation among infection type subsets. PMID- 27394638 TI - Inhibitory activity of avibactam against selected beta-lactamases expressed in an isogenic Escherichia coli strain. AB - Avibactam restored the in-vitro antibacterial activity of ceftazidime, ceftaroline, and aztreonam against isogenic Escherichia coli expressing class A, class C, and class D beta-lactamases. The enzymes included TEM and CTX-M extended spectrum beta-lactamases, ACT, CMY and FOX AmpC-type enzymes, and carbapenemases including rarer KPC variants and OXA-139. PMID- 27394639 TI - Validation of Minim typing for fast and accurate discrimination of extended spectrum, beta-lactamase-producing Klebsiella pneumoniae isolates in tertiary care hospital. AB - Minim typing is derived from the multi-locus sequence typing (MLST). It targets the same genes, but sequencing is replaced by high resolution melt analysis. Typing can be performed by analysing six loci (6MelT), four loci (4MelT) or using data from four loci plus sequencing the tonB gene (HybridMelT). The aim of this study was to evaluate Minim typing to discriminate extended-spectrum beta lactamase producing Klebsiella pneumoniae (ESBL-KLPN) isolates at our hospital. In total, 380 isolates were analyzed. The obtained alleles were assigned according to both the 6MelT and 4MelT typing scheme. In 97 isolates, the tonB gene was sequenced to enable HybridMelT typing. We found that the presented method is suitable to quickly monitor isolates of ESBL-KLPN; results are obtained in less than 2 hours and at a lower cost than MLST. We identified a local ESBL KLPN outbreak and a comparison of colonizing and invasive isolates revealed a long term colonization of patients with the same strain. PMID- 27394640 TI - Editorial Introduction to the 19(th) World Conference on Non-Destructive Testing (WCNDT-2016). PMID- 27394641 TI - Modeling Human Leukemia Immunotherapy in Humanized Mice. AB - The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse) model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL), which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI), a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia. PMID- 27394643 TI - Risk stratification in intermediate-risk acute pulmonary embolism. PMID- 27394642 TI - Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves. AB - Individuals with bicuspid aortic valves (BAV) are at a higher risk of developing thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV). The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest (NC) and paraxial mesoderm (PM), respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs)-derived SMCs but not paraxial mesoderm cells (PMCs)-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs) from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11) and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-beta signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC derived SMCs may contribute to that aortopathy associated with BAV. PMID- 27394645 TI - Corrigendum to "When continuous observations just won't do: Developing accurate and efficient sampling strategies for the laying hen" [Behav. Process. 103 (2014) 58-66]. PMID- 27394644 TI - Preoperative Membranous Urethral Length Measurement and Continence Recovery Following Radical Prostatectomy: A Systematic Review and Meta-analysis. AB - CONTEXT: Membranous urethral length (MUL) measured prior to radical prostatectomy (RP) has been identified as a factor that is associated with the recovery of continence following surgery. OBJECTIVE: To undertake a systematic review and meta-analysis of all studies reporting the effect of MUL on the recovery of continence following RP. EVIDENCE ACQUISITION: A comprehensive search of PubMed, EMBASE, and Scopus databases up to September 2015 was performed. Thirteen studies comprising one randomized controlled trial and 12 cohort studies were selected for inclusion. EVIDENCE SYNTHESIS: Four studies (1738 patients) that reported hazard ratio results. Every extra millimeter (mm) of MUL was associated with a faster return to continence (hazard ratio: 1.05; 95% confidence interval [CI]: 1.02-1.08, p<0.001). Eleven studies (6993 patients) reported the OR (OR) for the return to continence at one or more postoperative time points. MUL had a significant positive effect on continence recovery at 3 mo (OR: 1.08, 95% CI: 1.03-1.14, p=0.004), 6 mo (OR: 1.12, 95% CI: 1.09-1.15, p<0.0001). and 12 mo (OR: 1.12, 95% CI: 1.03-1.22, p=0.006) following surgery. After adjusting for repeated measurements over time and studies with overlapping data, all OR data combined indicated that every extra millimeter of MUL was associated with significantly greater odds for return to continence (OR: 1.09, 95% CI: 1.05-1.15, p<0.001). CONCLUSIONS: A greater preoperative MUL is significantly and positively associated with a return to continence in men following RP. Magnetic resonance imaging measurement of MUL is recommended prior to RP. PATIENT SUMMARY: We examined the effect that the length of a section of the urethra (called the membranous urethra) had on the recovery of continence after radical prostatectomy surgery. Our results indicate that measuring the length of the membranous urethra via magnetic resonance imaging before surgery may be useful to predict a longer period of urinary incontinence after surgery, or to explain a delay in achieving continence after surgery. PMID- 27394646 TI - The global burden of viral hepatitis: better estimates to guide hepatitis elimination efforts. PMID- 27394648 TI - Synthesis, characterization, and antifungal property of chitosan ammonium salts with halogens. AB - In this study, a group of novel water soluble chitosan ammonium salts with halogens were successfully synthesized, including chitosan-bromoacetate (CSB), chitosan-chloroacetate (CSC), chitosan-dichloroacetate (CSDC), chitosan trichloroacetate (CSTC), and chitosan-trifluoroacetate (CSTF), and their antifungal activities against three kinds of phytopathogens were comparatively estimated by hypha measurement in vitro, respectively. The fungicidal assessment revealed that the synthesized chitosan derivatives had higher antifungal activity than chitosan. Especially, the inhibitory indices of CSTC and CSTF against three kinds of phytopathogens were higher than 70% at 1.0mg/mL. Generally, the antifungal activity decreased in the order: CSTF>CSTC>CSDC>CSC>CSB>chitosan. Apparently, the order of antifungal activity was consistent with the electronegativity of different substituted groups with halogens. The substituted groups with stronger electronegativity could augment the positive charge densities of cationic amino groups by drawing more electrons from the cationic amino groups of chitosan ammonium salts, which demonstrated that the protonation of amino groups was significant for the antifungal activity of chitosan derivatives. PMID- 27394647 TI - The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. AB - BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0.89 million (95% uncertainty interval [UI] 0.86-0.94) to 1.45 million (1.38-1.54); YLLs from 31.0 million (29.6-32.6) to 41.6 million (39.1 44.7); YLDs from 0.65 million (0.45-0.89) to 0.87 million (0.61-1.18); and DALYs from 31.7 million (30.2-33.3) to 42.5 million (39.9-45.6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation. PMID- 27394649 TI - Mechanism of the cytotoxic effect of l-amino acid oxidase isolated from Bothrops alternatus snake venom. AB - BaltLAAO-I, an L-amino acid oxidase isolated from Bothrops alternatus, is a glycoprotein enzyme with a pI-5.3, 15% sugar and a related molecular mass of 66,000Da in its monomeric form, and 123,000Da in its dimeric form. The objective of this study is to describe the cytotoxicity activity induced by BaltLAAO-I isolated from Bothrops alternatus venom and its possible mechanism of action on tumor cells. Our results clearly depict that BaltLAAO-I has a strong selective cytotoxic activity on tumor cell lines (JURKAT, SK-BR-3 and B16F10). On the other hand, the results show low cytotoxicity on human peripheral blood mononuclear cells. Furthermore, our findings demonstrate that BaltLAAO-I induces the apoptosis of tumor cell lines through a cytotoxic activity exerted by a generation of reactive oxygen intermediates. All in all, the data indicate that LAAOs exert a selective cytotoxic role on tumor cells, demonstrating a great potential for future use in clinical therapy. PMID- 27394650 TI - Optic nerve integrity as a visuospatial cognitive predictor in Parkinson's disease. AB - OBJECTIVE: To explore the microstructural integrity of the optic nerve and its role as a cognitive predictor in patients with de novo Parkinson's disease (PD) using diffusion tensor image-based magnetic resonance scans. METHODS: We enrolled 82 patients with de novo PD, 36 patients with drug-induced parkinsonism (DIP), and 36 controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured on the mid-portion of the intraorbital optic nerve. Using a multivariate analysis of variance with repeated measures, longitudinal changes in cognitive subscores of a comprehensive neuropsychological test were evaluated in PD patients according to optic nerve integrity. RESULTS: The mean FA value in PD was significantly lower (0.552 +/- 0.103, p < 0.001) than that in DIP (0.645 +/- 0.099) or the controls (0.689 +/- 0.089), whereas the mean ADC value was significantly higher in the PD group compared to the DIP or control group (p < 0.001). Optic nerve integrity was not associated with parkinsonian motor severity, striatal dopamine transporter activity, olfaction, or baseline cognitive performance in PD patents. In a longitudinal assessment of cognition in PD, the lower FA group showed significant decline in the performance of Clock Drawing Test (F = 3.39, p = 0.038), but no significant differences in the other cognitive subsets. CONCLUSION: This study demonstrated that microstructural integrity in the optic nerve was distorted in PD patients, and that this nerve integrity might act as a cognitive predictor of visuospatial dysfunction. PMID- 27394651 TI - Prototheca species and Pithomyces chartarum as Causative Agents of Rhinitis and/or Sinusitis in Horses. AB - Pyogranulomatous rhinitis associated with an algal infection was diagnosed in a 25-year-old gelding and a 23-year-old mare had necrotizing sinusitis with intralesional algae and pigmented fungi. Algae were identified immunohistochemically in both cases as Prototheca spp. In the gelding, further characterization by polymerase chain reaction and sequencing revealed that the organism was Prototheca zopfii genotype 2. Fungi from the mare were identified as Pithomyces chartarum by molecular analysis. Prototheca species are achlorophyllous algae and P. chartarum represents a dematiaceous fungus; they are saprophytes and facultative pathogens. Prototheca spp. and P. chartarum should be considered as rare respiratory pathogens of horses. PMID- 27394652 TI - Outcome of Second Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Lymphoblastic Leukemia. AB - BACKGROUND: The outcome of patients with acute lymphoblastic leukemia (ALL) relapsing after allogeneic hematopoietic cell transplantation (AlloHCT) is poor. Although morphologic remission can sometimes be achieved, such remissions are usually transient if not consolidated by a second AlloHCT (AlloHCT2). MATERIALS AND METHODS: We retrospectively analyzed the outcomes of 27 patients with ALL who had undergone AlloHCT2 for relapsed disease at our center during a 12-year period. RESULTS: With a median follow-up of 50.9 months for living patients, the 2-year overall and event-free survival were 40.7% and 29.6%, respectively. Patients with either a disease-free interval or interval between transplants of > 1 year had better overall survival (P = .02 and P = .0005) after AlloHCT2. CONCLUSION: AlloHCT2 remains a potential curative option in a subset of patients with relapsed ALL after the first AlloHCT. PMID- 27394654 TI - Trans fatty acids and cholesterol levels: An evidence map of the available science. AB - High intakes of industrial trans fatty acids (iTFA) increase circulating low density lipoprotein cholesterol (LDL-C) levels, which has implicated iTFA in coronary heart disease (CHD) risk. Published data on iTFA and LDL-C, however, represent higher intake levels than the U.S. population currently consume. This study used state-of-the-art evidence mapping approaches to characterize the full body of literature on LDL-C and iTFA at low intake levels. A total of 32 independent clinical trials that included at least one intervention or control group with iTFA at <=3%en were found. Findings indicated that a wide range of oils and interventions were used, limiting the ability to determine an isolated effect of iTFA intake. Few data points were found for iTFA at <3%en, with the majority of low-level exposures actually representing control group interventions containing non-partially hydrogenated (PHO) oils. Further, it appears that few dose-response data points are available to assess the relationship of low levels of iTFA, particularly from PHO exposure, and LDL-C. Therefore, limited evidence is available to determine the effect of iTFA at current consumption levels on CHD risk. PMID- 27394653 TI - Predictive value of low serum pancreatic enzymes in invasive intraductal papillary mucinous neoplasms. AB - BACKGROUND: Despite evidence suggesting a role of chronic pancreatitis in pancreatic carcinogenesis, its relationship with invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. Low levels of pancreatic enzymes are predictive markers of advanced chronic pancreatitis. We investigated whether low pancreatic enzyme levels were associated with a higher incidence of invasive IPMN. METHODS: This study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Multivariable logistic regression analysis was conducted to assess the association between serum pancreatic enzymes and the incidence of invasive IPMN, with adjustment for clinical characteristics including alcohol consumption. The association of serum pancreatic enzymes with pathological pancreatic atrophy and inflammation in areas adjacent to or distant from the tumor was also evaluated. RESULTS: Low serum levels of pancreatic amylase and lipase were associated with a higher incidence of invasive IPMN (multivariable odds ratio [OR] = 9.6, 95% confidence interval [CI] = 2.99 to 35.1, P = 0.0001; OR = 14.2, 95% CI = 2.77 to 112, P = 0.001, respectively). Low serum pancreatic amylase and lipase levels were also associated with higher grade pancreatic atrophy in areas adjacent to the tumor (P = 0.011 and P = 0.017, respectively) and in areas distant from the tumor (P = 0.0002 and P = 0.001, respectively). Furthermore, low serum pancreatic amylase and lipase levels were associated with higher grade inflammation in areas distant from the tumor (P < 0.0001 and P = 0.001, respectively). CONCLUSIONS: Low serum pancreatic enzymes may be a predictive marker of invasive IPMN. Excessive alcohol consumption did not influence the association of low pancreatic enzyme levels with invasive IPMN. PMID- 27394655 TI - Modulating effect of losartan potassium on the mutagenicity and recombinogenicity of doxorubicin in somatic cells of Drosophila melanogaster. AB - Losartan potassium is an antihypertensive drug in the angiotensin II receptor antagonist (ARA) class. Some studies claim that, in addition to regulating blood pressure, this class of drug has anticancer properties. The objective of this study was to evaluate the genotoxic and antigenotoxic potential of losartan potassium using the SMART (Somatic Mutation and Recombination Test) assay on the somatic cells of Drosophila melanogaster, as well as the possible modulating effects of this drug, when associated with doxorubicin (DXR). Third instar larvae, descendents of standard and high bioactivation (ST and HB) crosses, were chronically treated with different concentrations of losartan potassium (0.25; 0.5; 1; 2; and 4 mM) alone or in association (co-treatment) with doxorubicin (DXR 0.125 mg/mL). The results showed an absence of a mutagenic effect of losartan potassium. In the co-treatment of losartan with DXR, the results showed that losartan is capable of reducing the number of mutant spots induced by DXR without altering the recombinogenic effect of the chemotherapeutic agent. Antiproliferative action appears to be the main mechanism involved in reducing the frequency of mutant spots and consequent modulation of alterations induced by DXR, although this parameter has not been directly assessed in this study. PMID- 27394656 TI - [Hypertensive disorders during pregnancy: Cardiovascular long-term outcomes]. AB - Pregnancy-induced hypertension (PIH) induces maternal and fetal damage, but it can also be the beginning of future metabolic and vascular disorders. The relative risk of chronic hypertension after PIH is between 2.3 and 11, and the likelihood of subsequent development of type 2 diabetes is multiplied by 1.8. Women with prior preeclampsia/eclampsia have a twofold risk of stroke and a higher frequency of arrhythmias and hospitalization due to heart failure. Furthermore, a tenfold greater risk for long-term chronic kidney disease is observed as well. The relative risk of cardiovascular death is 2.1 times higher compared to the group without pregnancy-induced hypertension problems, although the risk is between 4 and 7 times higher in preterm birth associated with gestational hypertension or pre-existing hypertension The postpartum period is a great opportunity to intervene on lifestyle, obesity, make an early diagnosis of chronic hypertension and DM and provide the necessary treatments to prevent cardiovascular complications in women. PMID- 27394657 TI - S-Nitrosothiols-NO donors regulating cardiovascular cell proliferation: Insight into intracellular pathway alterations. AB - Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) activates signaling pathways responsible for smooth muscle cell relaxation, leading to vasodilation and thus plays an important role in controlling vascular homeostasis, thrombosis and inflammation. Recent studies indicate that S nitrosothiols produced in vivo as well as synthetic ones might be important reservoirs of NO. Based on a broad range of NO functions within the living organisms, this review highlights the impact of S-nitrosothiols on cardiovascular cell cycle. The cell membrane transport and the decomposition patterns responsible of S-nitrosothiols actions are presented. The effects of NO delivery through S-nitrosothiols have a significant potential in cardiovascular diseases with various underlying causes. The challenges related to their application in the pharmacotherapy of patients with various cardiovascular diseases are also discussed. PMID- 27394658 TI - Cry1Ac toxin induces macrophage activation via ERK1/2, JNK and p38 mitogen activated protein kinases. AB - The Cry1Ac toxin from Bacillus thuringiensis is used commercially as a bio insecticide and is expressed in transgenic plants that are used for human and animal consumption. Although it was originally considered innocuous for mammals, the Cry1Ac toxin is not inert and has the ability to induce mucosal and systemic immunogenicity. Herein, we examined whether the Cry1Ac toxin promotes macrophage activation and explored the signalling pathways that may mediate this effect. Treatment of primary and RAW264.7 macrophages with the Cry1Ac toxin resulted in upregulation of the costimulatory molecules CD80, CD86 and ICOS-L and enhanced production of nitric oxide, the chemokine MCP-1 and the proinflammatory cytokines TNF-alpha and IL-6. Remarkably, the Cry1Ac toxin induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK1/2, JNK and p38 and promoted nuclear translocation of nuclear factor-kappa B (NF-kappaB) p50 and p65. p38 and ERK1/2 MAPKs were involved in this effect, as indicated by the Cry1Ac-induced upregulation of CD80 and IL-6 and TNF-alpha abrogation by the p38 MAPK inhibitor SB203580. Furthermore, treatment the MEK1/2 kinase inhibitor PD98059 blocked increases in MCP-1 secretion and augmented Cry1Ac-induced ICOS-L upregulation. These data demonstrate the capacity of the Cry1Ac toxin to induce macrophage activation via the MAPK and NF-kappaB pathways. PMID- 27394659 TI - Intermittent access to a sucrose solution for rats causes long-term increases in consumption. AB - Intermittent access to palatable food can elevate consumption beyond an animal's immediate needs. If adult male rats (with ad lib access to food and water) are provided with a 4% sucrose solution, daily sucrose consumption is determined by the sucrose access schedule: access that is intermittent leads to high levels of consumption. In Experiment 1, sucrose solutions were first provided continuously or every second, third, or fourth day for 23.5h over 49days. Continuous-access sucrose consumption averaged 102g per day, while that for access every fourth day averaged 294g. Daily consumption averages for access every second and third day fell between these two extremes. When all rats were then given alternate-day access to sucrose for 24days in Phase II, the previously established consumption differences were maintained. Body weight was unaffected by sucrose access; rats adjusted their food consumption so that total calorie intake remained constant. In Experiment 2, compared to continuous 4% sucrose solution access, access every third day markedly elevated daily sucrose consumption after only four sucrose exposures. With this shorter Phase I, sucrose intake in the continuous group increased markedly when in Phase II all rats were given alternate day access. In Experiment 3, a lick-by-lick analysis of the difference in sucrose consumption between access every third day and continuous access revealed that all rats were consuming a similar number of sucrose meals; however, the meals were larger both in the first hour and over the whole 24h with intermittent access. This suggests a change in satiety as a mechanism underlying sucrose consumption difference. PMID- 27394660 TI - Expression of arginine vasotocin and estrogen receptor alpha (ERalpha) in the shell gland altered by the specific phase relations of neural oscillations affects the reproductive physiology of Japanese quail. AB - In order to study the effect of specific phase relation of neural oscillations on reproductive regulation and the response of AVT (the avian homologue of mammalian AVP) the expression of AVT in the shell gland was monitored in sexually immature quail. In this study 3-week-old female Japanese quail were administered with serotonin precursor, 5-hydroxytryptophan followed by the dopamine precursor, l dihydroxyphenylalanine at interval of 8h and 12h daily over a period of 13days. At thirty two days post treatment, a significant decrease in gonadal activity was seen in 8h quail although 12h quail exhibited an increase as compared to controls. A significant decrease in plasma estradiol level was noted in 8h quail while 12h exhibited no significant difference compared to controls. To address the relative roles of estrogen mediated action we also investigated estrogen receptor alpha (ER-alpha) expression and localization in the shell gland by visualizing it through confocal immuno-fluorescence microscopy. Results indicate increased expression of immunoreactive (ir)-AVT (myometrium), ir-ER-alpha (epithelial cells of endometrial region), along with significant increase in hypothalamic, plasma and shell gland AVT and a rapid increase in egg laying thus maintaining full breeding condition in 12h while low expression of ir-AVT and ir ER-alpha was observed in 8h quail along with a significant decrease in hypothalamic, plasma and shell gland AVT with the suppression of gonads thereby stopping the egg-laying behaviour was noted. These findings not only suggest the modulation of gonadal development by changing the specific phase relation of neural oscillations but also demonstrate a parallel relation of AVT and gonadal activity in both conditions. It is concluded that the egg laying performance in response to AVT is regulated by the temporal phase relationship of neurotransmitters, and in part, this effect appears to be estrogen dependent. PMID- 27394661 TI - Preschoolers' distress and regulatory behaviors vary as a function of infant mother attachment security. AB - Children (N=98) with higher attachment security scores, and lower resistance and avoidance scores during the Strange Situation at 16 months demonstrated somewhat more adaptive observed and mother-reported emotion regulation as preschoolers independent of maternal behavior. PMID- 27394662 TI - BMP9 a possible alternative drug for the recently withdrawn BMP7? New perspectives for (re-)implementation by personalized medicine. AB - Promotion of rhBMP2 and rhBMP7 for the routine use to support fracture healing has been hampered by high costs, safety concerns and reasonable failure rates, imposing restrictions in its clinical use. Since there is little debate regarding its treatment potential, there is rising need for a better understanding of the mode of action of these BMPs to overcome its drawbacks and promote more efficacious treatment strategies for bone regeneration. Recently, BMP9, owing to its improved osteogenic potential, is gaining attention as a promising therapeutic alternative. Our study aimed at identifying specific gene expression patterns which may predict and explain individual responses to rhBMP7 and rhBMP9 treatments. Therefore, we investigated the effect of rhBMP7 and rhBMP9 on primary human osteoblasts from 110 donors and corresponding THP-1-derived osteoclasts. This was further compared with each other and our reported data on rhBMP2 response. Based on the individual donor response, we found three donor groups profiting from rhBMP treatment either directly via stimulation of osteoblast function or viability and/or indirectly via inhibition of osteoclasts. The response on rhBMP7 treatment correlated with expression levels of the genes BAMBI, SOST, Noggin, Smad4 and RANKL, while the response of rhBMP9 correlated to the expression levels of Alk6, Endoglin, Smurf1, Smurf2, SOST and RANKL in these donors. Noteworthy, rhBMP9 treatment showed significantly increased osteogenic activity (AP activity and Smad nuclear translocation) when compared to the two clinically used rhBMPs. Based on patient's respective expression profiles, clinical application of rhBMP9 either solely or in combination with rhBMP2 and/or rhBMP7 can become a promising new approach to fit the patient's needs to promote fracture healing. PMID- 27394664 TI - Effect of obesity on cost per quality-adjusted life years gained following anterior cervical discectomy and fusion in elective degenerative pathology. AB - BACKGROUND: Obese patients have greater comorbidities along with higher risk of complications and greater costs after spine surgery, which may result in increased cost and lower quality of life compared with their non-obese counterparts. PURPOSE: The aim of the present study was to determine cost-utility following anterior cervical discectomy and fusion (ACDF) in obese patients. STUDY DESIGN: This study analyzed prospectively collected data. PATIENT SAMPLE: Patients undergoing elective ACDF for degenerative cervical pathology at a single academic institution were included in the study. OUTCOME MEASURES: Cost and quality-adjusted life years (QALYs) were the outcome measures. METHODS: One- and two-year medical resource utilization, missed work, and health state values (QALYs) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national payment amounts (direct cost). Patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Total cost (direct+indirect) was used to compute cost per QALY gained. Patients were defined as obese for body mass index (BMI) >=35 based on the WHO definition of class II obesity. A subgroup analysis was conducted in morbidly obese patients (BMI>=40). RESULTS: There were significant improvements in pain (neck pain or arm pain), disability (Neck Disability Index), and quality of life (EuroQol-5D and Short Form-12) at 2 years after surgery (p<.001). There was no significant difference in post-discharge health-care resource utilization, direct cost, indirect cost, and total cost between obese and non-obese patients at postoperative 1-year and 2-year follow-up. Mean 2-year direct cost for obese patients was $19,225+/-$8,065 and $17,635+/-$6,413 for non-obese patients (p=.14). There was no significant difference in the mean total 2-year cost between obese ($23,144+/-$9,216) and non-obese ($22,183+/-$10,564) patients (p=.48). Obese patients had a lower mean cumulative gain in QALYs versus non obese patients at 2-years (0.34 vs. 0.42, p=.32). Two-year cost-utility in obese ($68,070/QALY) versus non-obese patients ($52,816/QALY) was not significantly different (p=.11). Morbidly obese patients had lower QALYs gained (0.17) and higher cost per QALYs gained ($138,094/QALY) at 2 years. CONCLUSIONS: Anterior cervical discectomy and fusion provided a significant gain in health state utility in obese patients, with a mean 2-year cost-utility of $68,070 per QALYs gained, which can be considered moderately cost-effective. Morbidly obese patients had lower cost-effectiveness; however, surgery does provide a significant improvement in outcomes. Obesity, and specifically morbid obesity, should to be taken into consideration as physician and hospital reimbursements move toward a bundled model. PMID- 27394663 TI - The p21-activated kinase (PAK1) is involved in diet-induced beta cell mass expansion and survival in mice and human islets. AB - AIMS/HYPOTHESIS: Human islets from type 2 diabetic donors are reportedly 80% deficient in the p21 (Cdc42/Rac)-activated kinase, PAK1. PAK1 is implicated in beta cell function and maintenance of beta cell mass. We questioned the mechanism(s) by which PAK1 deficiency potentially contributes to increased susceptibility to type 2 diabetes. METHODS: Non-diabetic human islets and INS 832/13 beta cells cultured under diabetogenic conditions (i.e. with specific cytokines or under glucolipotoxic [GLT] conditions) were evaluated for changes to PAK1 signalling. Combined effects of PAK1 deficiency with GLT stress were assessed using classic knockout (Pak1 (-/-) ) mice fed a 45% energy from fat/palmitate-based, 'western' diet (WD). INS 832/13 cells overexpressing or depleted of PAK1 were also assessed for apoptosis and signalling changes. RESULTS: Exposure of non-diabetic human islets to diabetic stressors attenuated PAK1 protein levels, concurrent with increased caspase 3 cleavage. WD-fed Pak1 knockout mice exhibited fasting hyperglycaemia and severe glucose intolerance. These mice also failed to mount an insulin secretory response following acute glucose challenge, coinciding with a 43% loss of beta cell mass when compared with WD-fed wild-type mice. Pak1 knockout mice had fewer total beta cells per islet, coincident with decreased beta cell proliferation. In INS 832/13 beta cells, PAK1 deficiency combined with GLT exposure heightened beta cell death relative to either condition alone; PAK1 deficiency resulted in decreased extracellular signal-related kinase (ERK) and B cell lymphoma 2 (Bcl2) phosphorylation levels. Conversely, PAK1 overexpression prevented GLT-induced cell death. CONCLUSIONS/INTERPRETATION: These findings suggest that PAK1 deficiency may underlie an increased diabetic susceptibility. Discovery of ways to remediate glycaemic dysregulation via altering PAK1 or its downstream effectors offers promising opportunities for disease intervention. PMID- 27394666 TI - Inhibitors of diacylglycerol lipases in neurodegenerative and metabolic disorders. AB - 2-Arachidonoylglycerol (2-AG) is an endocannabinoid that activates the cannabinoid receptors type 1 and 2. It also serves as an important lipid precursor for the eicosanoid signaling pathway. Consequently, 2-AG is involved in many physiological functions, including anxiety, food intake, inflammation, memory, pain sensation and neurotransmission. Diacylglycerol lipases (DAGLs) are the main biosynthetic enzymes for 2-AG and their role in several pathophysiological conditions is currently under investigation. In this Digest we review all DAGL inhibitors reported to date and their effects in preclinical models of neurodegeneration and metabolic disorders. PMID- 27394665 TI - Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742. AB - Herein we describe our research efforts around the aryl and heteroaryl substitutions at the aminal carbon of the tetracyclic indole-based HCV NS5A inhibitor MK-8742. A series of potent NS5A inhibitors are described, such as compounds 45-47, 54, 56, and 65, which showed improved potency against clinically relevant and resistance associated HCV variants. The improved potency profiles of these compounds demonstrated an SAR that can improve the potency against GT2b, GT1a Y93H, and GT1a L31V altogether, which was unprecedented in our previous efforts in NS5A inhibition. PMID- 27394667 TI - Effect of shorter dark adaptation on ISCEV standard DA 0.01 and DA 3 skin ERGs in healthy adults. AB - PURPOSE: To quantify dark-adapted (DA) skin ERG changes during 20 min of dark adaptation. METHODS: Sixteen healthy adult subjects were dark-adapted for 20 min during which ISCEV standard dim (0.01 phot cd s m(-2)) white flash ERGs were recorded at 1, 2, 3, 4, 5, 10, 15 and 20 min, and bright (3 phot cd s m(-2)) white ERGs were recorded at 2, 5, 10, 15 and 20 min without mydriasis and using skin electrodes. Amplitudes and peak times were normalised to 20 min values. RESULTS: Halving dark adaptation from 20 to 10 min had no measureable effect on the DA 3 ERG and caused a 10 % amplitude loss (range 0-23 %) only for the DA 0.01 ERG b-wave amplitude. No significant peak time changes resulted, nor increased parameter variability. CONCLUSION: Reducing dark adaptation from 20 to 10 min or even less has an effect on only DA 0.01 ERGs. Shorter dark adaptation than 20 min may not compromise the clinical utility of the ERG providing clinics adhere to the usual standards of adequate reference data. PMID- 27394669 TI - Cerebral functional deficits in patients with ankylosing spondylitis- an fMRI study. AB - Neurological impairment plays an important role in the development of Ankylosing spondylitis (AS). Early diagnosis and detection of it may stop the progress of neurological complications and improve the quality of patients' lives greatly. Somatosensory evoked potential (SSEP) and magnetic motor evoked potentials (MEP) have been proved useful to detect neurological impairments of AS. This study aimed to investigate the cerebral function deficits of AS using functional MRI technology. Twenty seven patients with AS and 28 control subjects were included in this study. All of them underwent structural MRI and resting state-functional MRI (rs-fMRI) scanning. Comparisons of amplitude of low frequency fluctuations (ALFF) of rs-fMRI signals between AS patients and normal controls were performed using two sample t-tests. To examine functional connectivity within the groups, one-sample t tests were performed on the individual z-value maps. The z values were compared between the two groups using two-sample t test. Partial correlations between rs-fMRI measures (ALFF and functional connectivity) of the brain regions which showed group difference and clinical results including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, the serum high sensitivity C-reactive protein (hsCRP), and the erythrocyte sedimentation rate (ESR) were analyzed for AS patients. Compared with normal controls, the AS patients exhibited significant lower ALFF in the left medial frontal gyrus, the right precentral gyrus and the right posterior cingulate, while higher ALFF in the left cerebellum anterior lobe, the left middle temporal gyrus, the left superior occipital gyrus, the left postcentral gyrus and the right precuneus. AS patients showed widespread brain connectivity alterations. Functional connectivity strength of the left precuneus and the left middle temporal gyrus were closely correlated with the the BASDAI scores, ESR and hsCRP in AS patients. Our results enhance the understanding of the pathomechanism of AS and suggest that Rs-fMRI may be a helpful tool in the clinical detection and evaluation of neurological impairment in AS. PMID- 27394668 TI - Applications of imaging flow cytometry in the diagnostic assessment of acute leukaemia. AB - Automated imaging flow cytometry integrates flow cytometry with digital microscopy to produce high-resolution digital imaging with quantitative analysis. This enables cell identification based on morphology (cell size, shape), antigen expression, quantification of fluorescence signal intensity and localisation of detected signals (i.e. surface, cytoplasm, nuclear). We describe applications of imaging flow cytometry for the diagnostic assessment of acute leukaemia. These bone marrow malignancies are traditionally diagnosed and classified by cell morphology, phenotype and cytogenetic abnormalities. Traditionally morphology is assessed by light microscopy, phenotyping by conventional flow cytometry and genetics by karyotype and fluorescence in situ hybridisation (FISH) on interphase nuclei/metaphase spreads of cells on slides. Imaging flow cytometry adds a new dimension to the diagnostic assessment of these neoplasms. We describe three specific applications: From this we conclude that imaging flow cytometry offers benefits over conventional diagnostic methods. Specifically the ability to visualise the cells of interest, the pattern and localisation of expressed antigens and assess cytogenetic abnormalities in one integrated automated high throughput test. Imaging flow cytometry presents a new paradigm for the diagnostic assessment of leukaemia. PMID- 27394670 TI - Review on the Role of Planetary Factors on Habitability. AB - In this work various factors on the habitability were considered, focusing on conditions irrespective of the central star's radiation, to see the role of specific planetary body related effects. These so called planetary factors were evaluated to identify those trans-domain issues where important information is missing but good chance exit to be filled by new knowledge that might be gained in the next decade(s). Among these strategic knowledge gaps, specific issues are listed, like occurrence of radioactive nucleides in star forming regions, models to estimate the existence of subsurface liquid water from bulk parameters plus evolutionary context of the given system, estimation on the existence of redox gradient depending on the environment type etc. These issues require substantial improvement of modelling and statistical handling of various cases, as "planetary environment types". Based on our current knowledge it is probable that subsurface habitability is at least as frequent, or more frequent than surface habitability. Unfortunately it is more difficult from observations to infer conditions for subsurface habitability, but specific argumentation might help with indirect ways, which might result in new methods to approach habitability in general. PMID- 27394671 TI - The dilemma of arranged marriages in people with epilepsy. An expert group appraisal. AB - INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored. PMID- 27394672 TI - How many patients with rheumatic diseases and TNF inhibitors treatment have latent tuberculosis? AB - OBJECTIVES: Spanish clinical guidelines recommend screening patients for tuberculosis (TB) before TNF inhibitors (TNFi) treatment. Our objective was to estimate the prevalence of TST seroconversion as an estimation of the prevalence of latent TB in patients with rheumatic diseases and TNFi treatment that have already been screened for tuberculosis. METHODS: TST, booster and chest x-ray were performed to patients with rheumatic diseases, TNFi treatment, negative tuberculin skin tests before treatment and that were attending the rheumatology Department of three different hospitals in Barcelona. According to the Spanish Society Rheumatology guidelines, these patients had not received TB prophylaxis treatment. RESULTS: One hundred and forty patients were included in the study. The tuberculin skin test was positive in 4.28% (n=6) of the patients. 50% of the patients were undergoing TNFi <= 2 years, being two of the patients only one year on the TNFi when a positive TST was detected. This shows that a conversion of the TST can occur even few months or years after the TNFi is started. CONCLUSIONS: The present study observed that 4.28% of patients with rheumatic diseases on TNFi who did not have performed a pre-treatment TB prophylaxis, had a conversion of the TST. Moreover, the conversion of the TST had been within the first two years of treatment in half of the patients of our cohort. In spite of these results, false TST positives in the diagnosis of latent TB cannot be excluded as an explanation for our results. PMID- 27394673 TI - Measurement model choice influenced randomized controlled trial results. AB - OBJECTIVE: In randomized controlled trials (RCTs), outcome variables are often patient-reported outcomes measured with questionnaires. Ideally, all available item information is used for score construction, which requires an item response theory (IRT) measurement model. However, in practice, the classical test theory measurement model (sum scores) is mostly used, and differences between response patterns leading to the same sum score are ignored. The enhanced differentiation between scores with IRT enables more precise estimation of individual trajectories over time and group effects. The objective of this study was to show the advantages of using IRT scores instead of sum scores when analyzing RCTs. STUDY DESIGN AND SETTING: Two studies are presented, a real-life RCT, and a simulation study. Both IRT and sum scores are used to measure the construct and are subsequently used as outcomes for effect calculation. RESULTS: The bias in RCT results is conditional on the measurement model that was used to construct the scores. A bias in estimated trend of around one standard deviation was found when sum scores were used, where IRT showed negligible bias. CONCLUSION: Accurate statistical inferences are made from an RCT study when using IRT to estimate construct measurements. The use of sum scores leads to incorrect RCT results. PMID- 27394674 TI - Which estimates comprise optimal reporting in Systematic Reviews? PMID- 27394675 TI - Prognostic model for advanced breast carcinoma with luminal subtype and impact of hormonal maintenance: Implications for post-progression and conditional survival. AB - BACKGROUND: The aim of this analysis was to develop and validate a prognostic model for advanced breast cancer (ABC) with luminal subtype based on the combination of clinical, pathological and therapeutic predictors to provide a practical tool to evaluate patients' prognosis. METHODS: Clinical and pathological data were retrospectively correlated to progression-free and overall survival (PFS/OS) using a Cox model. Significant treatment variables were adjusted with the propensity score analysis. A continuous score to identify risk classes was derived according to model ratios. The performance of the risk-class model was tested for post-progression survival (PPS) and conditional survival (CS) as well. RESULTS: Data from 335 patients (3 institutions) were gathered (median follow-up 58 months). At multivariate analysis Ki67, Performance Status (PS) and number of metastatic sites were significant predictors for PFS, whereas Ki67, PS, brain metastases, PFS after 1st-line therapy, number of chemotherapy lines, hormonal therapy and maintenance were significant predictors for OS. The hormonal maintenance resulted to be prognostic after adjustment with propensity score analysis. A two-class model significantly differentiated low-risk and high risk patients for 2-year PFS (31.5% and 11.0%, p < 0.0001), and 3-years OS (57.1% and 4.8%, p < 0.0001). A three-class model separated low risk, intermediate-risk, and high-risk patients for 2-year PFS (40.8%, 24.4%, and 11.0%, p < 0.0001) and 3 year OS (68.1%, 24.8%, and 4.8%, p < 0.0001). Both models equally discriminate the luminal ABC prognosis in terms of PPS and CS. CONCLUSIONS: A risk stratification model including 'easy-to-obtain' clinical, pathological and therapeutic parameters accurately separates luminal ABC patients into different risk classes. PMID- 27394676 TI - A prospective study on the neurological complications of breast cancer and its treatment: Updated analysis three years after cancer diagnosis. AB - OBJECTIVES: To quantify the prevalence of neurological complications among breast cancer patients at one and three years after diagnosis, and to identify factors associated with neuropathic pain (NP) and chemotherapy-induced peripheral neuropathy (CIPN). MATERIAL AND METHODS: Prospective cohort study including 475 patients with newly diagnosed breast cancer, recruited among those proposed for surgical treatment (Portuguese Institute of Oncology, Porto). Patients underwent a neurological evaluation and had their cognitive function assesses with the Montreal Cognitive Assessment, before treatment and at one and three years after enrollment. We estimated the prevalence of each neurological complication, and odds ratios (OR), adjusted for socio-demographic and clinical characteristics, to identify factors associated with NP and CIPN. RESULTS: More than half of the patients [54.7%, 95% confidence interval (95%CI): 50.2-59.2] presented at least one neurological complication, at one or at three years after cancer diagnosis. Between the first and the third year of follow-up, there was an increase in the prevalence of NP (from 21.1% to 23.6%), cognitive impairment (from 7.2% to 8.2%), cerebrovascular disease (from 0.6% to 1.5%) and brain metastasis (from 0.0% to 0.6%). The prevalence of CIPN decreased from 14.1% to 12.6%. Axillary lymph node dissection was associated with NP at one year (OR = 2.75, 95%CI: 1.34-5.63) and chemotherapy with NP at three years (OR = 2.10, 95%CI: 1.20-3.67). Taxane-based chemotherapy was strongly associated with prevalence of CIPN at one and three years. CONCLUSION: Neurological complications are frequent even three years after cancer diagnosis and NP remained the major contributor to the burden of these conditions among survivors. PMID- 27394677 TI - Electronic patient records, past, present and future. AB - The health informatics revolution was spear-headed in the 1980s by pioneers in primary care who worked in an opportune environment and were able to successfully implement electronic patient records (EPR) as far back as the 1990s. Although the ambitious and costly National Programme for IT failed to deliver an integrated EPR, the project achieved the creation of the Spine, the N3 Network, choose and book, picture archiving, communication systems and standards which have allowed integration. Real change is taking place within the NHS with the launch of exciting new projects focusing on true integration and secure data flows across primary, community and secondary care. These changes have been brought about by the realisation that linking "best in class" is more likely to secure a successful cost-effective national integrated EPR. PMID- 27394678 TI - Racial and socio-economic disparities in breast cancer hospitalization outcomes by insurance status. AB - BACKGROUND: Breast cancer remains a major cause of morbidity and mortality among women in the US, and despite numerous studies documenting racial disparities in outcomes, the survival difference between Black and White women diagnosed with breast cancer continues to widen. Few studies have assessed whether observed racial disparities in outcomes vary by insurance type e.g. Medicare/Medicaid versus private insurance. Differences in coverage, availability of networked physicians, or cost-sharing policies may influence choice of treatment and treatment outcomes, even after patients have been hospitalized, effects of which may be differential by race. PURPOSE: The aim of this analysis was to examine hospitalization outcomes among patients with a primary diagnosis of breast cancer and assess whether differences in outcome exist by insurance status after adjusting for age, race/ethnicity and socio-economic status. METHODS: We obtained data on over 67,000 breast cancer patients with a primary diagnosis of breast cancer for this cross-sectional study from the 2007-2011 Healthcare Cost and Utilization project Nationwide Inpatient Sample (HCUP-NIS), and examined breast cancer surgery type (mastectomy vs. breast conserving surgery or BCS), post surgical complications and in-hospital mortality. Multivariable regression models were used to compute estimates, odds ratios and 95% confidence intervals. RESULTS: Black patients were less likely to receive mastectomies compared with White women (OR: 0.80, 95% CI: 0.71-0.90), regardless of whether they had Medicare/Medicaid or Private insurance. Black patients were also more likely to experience post-surgical complications (OR: 1.41, 95% CI: 1.12-1.78) and higher in-hospital mortality (OR: 1.57, 95%: 1.21-2.03) compared with White patients, associations that were strongest among women with Private insurance. Women residing outside of large metropolitan areas were significantly more likely to receive mastectomies (OR: 1.89, 95% CI: 1.54-2.31) and experience higher in hospital mortality (OR: 1.74, 95% CI: 1.40-2.16) compared with those in metropolitan areas, regardless of insurance type. CONCLUSION: Among hospitalized patients with breast cancer, racial differences in hospitalization outcomes existed and worse outcomes were observed among Black women with private insurance. Future studies are needed to determine factors associated with poor outcomes in this group of women, as well as to examine contributors to low BCS adoption in non-metropolitan areas. PMID- 27394679 TI - Open encapsulation-vitrification for cryopreservation of algae. AB - Vitrification offers a cost-effective solution for the preservation and management of genetic resources with, low-cost international movement of selected genetic materials and for long-term maintenance of stable stocks of a wide variety of microorganisms. However, its success is limited by the wide range of algal species. Here, we report a simple open encapsulation-vitrification protocol of cryopreservation. Results showed that ~58% and ~27% of Oocystis sp. survived vitrification-warming after the open and closed system of vitrification respectively when compared to non-cryopreserved controls. The improved success in an open system of vitrification was also observed in Anabaena sp. Furthermore, with the addition of 2-mercaptoethanol or glutathione the post-warming viability of vitrified algae in both open and closed system of vitrification was significantly improved (p < 0.05). The present case study aimed to develop a vitrification-based cryopreservation protocol and confirms an improvement in survival percentage over conventional encapsulation-vitrification method. PMID- 27394681 TI - Oral delivery of anti-MDM2 inhibitor SP141-loaded FcRn-targeted nanoparticles to treat breast cancer and metastasis. AB - We have recently discovered a specific Murine Double Minute 2 (MDM2) oncogene inhibitor, called SP141, which exerts potent anticancer activity in various breast cancer models. However, its low oral bioavailability is the major hurdle for moving this drug to clinical trial. The present study was designed to discover and validate a novel nano-oral delivery system for this promising anticancer agent. Herein, we report the preparation, characterization, and evaluation of the efficacy and safety of the SP141-loaded IgG Fc-conjugated maleimidyl-poly(ethylene glycol)-co-poly(epsilon-caprolactone) (Mal-PEG-PCL) nanoparticles (SP141FcNP) as an orally cancer therapeutic agent. Our results indicated that SP141FcNP showed a biphasic release pattern and increased transepithelial transport in vitro and in vivo with the involvement of FcRn mediated transcytosis. SP141FcNP also exhibited increased intestinal epithelial permeability, cellular uptake, and oral bioavailability, with extended blood circulation time, increased tumor accumulation, enhanced MDM2 inhibition, and stronger responses in anti-tumor growth and metastasis effects in vitro and in vivo, without apparent host toxicity. Collectively, this newly developed nanoparticle oral delivery system provides a basis for evaluation of SP141 as a potential clinical candidate for cancer therapy. PMID- 27394682 TI - Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers. AB - Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-term ex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for preclinical assessment of novel drug delivery systems at therapeutic doses in models of diseased skin. PMID- 27394683 TI - Splice-Site Mutation of Exon 3 Deletion in the Gamma-Glutamyl Carboxylase Gene Causes Inactivation of the Enzyme. PMID- 27394684 TI - Hearing Aid Use is Associated with Better Mini-Mental State Exam Performance. AB - OBJECTIVE: Hearing loss is associated with cognitive decline in the elderly. However, it is unknown if the use of hearing aids (HAs) is associated with enhanced cognitive function. METHODS: In a cross-sectional study at an academic medical center, participants underwent audiometric evaluation, the Mini-Mental State Exam (MMSE), and the Trail Making Test, Part B (TMT-B). The impact of use versus disuse of HAs was assessed. Performance on cognitive tests was then compared with unaided hearing levels. RESULTS: HA users performed better on the MMSE (1.9 points; rank-sum, p = 0.008) despite having worse hearing at both high frequencies (15.3-dB hearing level; t test, p < 0.001) and low frequencies (15.7 dB hearing level; t test p < 0.001). HA use had no effect TMT-B performance. Better performance on the MMSE was correlated with both low frequency (rho = 0.28, p = 0.021) and high frequency (rho = -0.21, p = 0.038) hearing level, but there was no correlation between performance on the TMT-B and hearing at any frequency. CONCLUSION: Despite having poorer hearing, HA users performed better on the MMSE. Better performance on cognitive tests with auditory stimuli (MMSE) but not visual stimuli (TMT-B) suggests that hearing loss is associated with sensory-specific cognitive decline rather than global cognitive impairment. Because hearing loss is nearly universal in those older than 80 years, HAs should be strongly recommended to minimize cognitive impairment in the elderly. PMID- 27394685 TI - Bony defects in chronic anterior posttraumatic dislocation of the shoulder: Is there a correlation between humeral and glenoidal lesions? AB - BACKGROUND: The prevalence of combined humeral and glenoid defects varies between 79 and 84 % in case of chronic posttraumatic anterior shoulder instability. The main goal of this study was to evaluate the relationship between humeral and glenoid defects based on quantitative radiological criteria. METHODS: A retrospective study was performed between 2000 and 2011 including patients who underwent primary surgical shoulder stabilization for chronic posttraumatic anterior shoulder instability, with bone defects in both the glenoid and humerus and a healthy contralateral shoulder. The following measurements were taken: D/R ratio (Hill-Sachs lesion depth/humeral head radius) on an AP X-ray in internal rotation and the D1/D2 ratio [diameter of the involved glenoid articular surfaces (D1)/the healthy one (D2)] on a comparative Bernageau glenoid profile view. Measurements were taken by two observers. Correlations were determined by the Spearman correlation coefficients (r), Bland and Altman diagrams, and intra-class correlation coefficients (ICC). A sample size calculation was done. RESULTS: Thirty patients were included, 25 men/5 women, mean age 29.8 +/- 11.2 years. The mean D/R was 23 +/- 12 % for observer 1 and 23 +/- 10 % for observer 2. The mean D1/D2 was 95 +/- 4 % for observer 1 and 94 +/- 6 % for observer 2. No significant correlation was found between humeral and glenoid bone defects by observer 1 (r = 0.23, p = 0.22) or observer 2 (r = 0.05, p = 0.78). Agreement of the observers for the D/R ratio was excellent (ICC = 0.89 +/- 0.04, p < 0.00001) and good for the D1/D2 ratio (ICC = 0.54 +/- 0.14, p = 0.006). CONCLUSION: Humeral and glenoid bone defects were not correlated. Inter-observer reliability was excellent for the D/R ratio and good for the D1/D2 ratio. LEVEL OF EVIDENCE: Nonconsecutive Patients, Diagnostic Study, Level III. PMID- 27394680 TI - Redox mechanisms in age-related lung fibrosis. AB - Redox signaling and oxidative stress are associated with tissue fibrosis and aging. Aging is recognized as a major risk factor for fibrotic diseases involving multiple organ systems, including that of the lung. A number of oxidant generating enzymes are upregulated while antioxidant defenses are deficient with aging and cellular senescence, leading to redox imbalance and oxidative stress. However, the precise mechanisms by which redox signaling and oxidative stress contribute to the pathogenesis of lung fibrosis are not well understood. Tissue repair is a highly regulated process that involves the interactions of several cell types, including epithelial cells, fibroblasts and inflammatory cells. Fibrosis may develop when these interactions are dysregulated with the acquisition of pro-fibrotic cellular phenotypes. In this review, we explore the roles of redox mechanisms that promote and perpetuate fibrosis in the context of cellular senescence and aging. PMID- 27394686 TI - Translation of BDNF-gene transcripts with short 3' UTR in hippocampal CA1 neurons improves memory formation and enhances synaptic plasticity-relevant signaling pathways. AB - While the brain-derived neurotrophic factor (BDNF) gene and its multiple transcripts have been recognized as a key factor for learning, but the specific involvement of BDNF translated from BDNF transcripts with short-3' untranslated region (short 3' UTR) in learning and memory requires further analysis. In this paper, we present data to show that the transduction of hippocampal CA1 neurons with AAV9-5' UTR-BDNF (short 3' UTR)-IRES-ZsGreen and the subsequent expression of BDNF enhanced the phosphorylation of synaptic plasticity relevant proteins and improved passive avoidance and object location, but not object recognition memory. In addition, BDNF improved the relearning of object location. At higher BDNF overexpression levels, the fear behavior was accompanied with a decline in the passive avoidance memory 24h post training, and with an enhanced fear conditioning performance. In addition, these animals developed spontaneous seizures. Thus, the expression of BDNF in the hippocampal CA1 region has the potential to improve fear and object location memory in wild type mouse strains when the region and expression levels of BDNF are well controlled. PMID- 27394687 TI - MDMA and PTSD treatment: "PTSD: From novel pathophysiology to innovative therapeutics". AB - There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment resistant PTSD. PMID- 27394688 TI - Retinal co-mediator acetylcholine evokes muscarinic inhibition of recurrent excitation in frog tectum column. AB - Acetylcholine receptors contribute to the control of neuronal and neuronal network activity from insects to humans. We have investigated the action of acetylcholine receptors in the optic tectum of Rana temporaria (common frog). Our previous studies have demonstrated that acetylcholine activates presynaptic nicotinic receptors, when released into the frog optic tectum as a co-mediator during firing of a single retinal ganglion cell, and causes: a) potentiation of retinotectal synaptic transmission, and b) facilitation of transition of the tectum column to a higher level of activity. In the present study we have shown that endogenous acetylcholine also activates muscarinic receptors, leading to a delayed inhibition of recurrent excitatory synaptic transmission in the tectum column. The delay of muscarinic inhibition was evaluated to be of ~80ms, with an extent of inhibition of ~2 times. The inhibition of the recurrent excitation determines transition of the tectum column back to its resting state, giving a functional sense for the inhibition. PMID- 27394690 TI - Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance. AB - PURPOSE: Dynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect. METHODS: 16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated. RESULTS: The change in PTV and organs at risk DVH parameters were 0.4 4.1%. Good correlation (>0.83) between the PTVmean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3mm (per beam and composite plan) and 3%G/2mm (composite plan) for the diode array phantom and 2%G/2mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6. CONCLUSIONS: A DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3mm per beam gamma setting. PMID- 27394689 TI - Retinal nerve fibre layer thickness changes in Alzheimer's disease: Results from a 12-month prospective case series. AB - PURPOSE: To compare the 12-month peripapillary retinal nerve fibre layer (pRNFL) thickness change between AD patients and normal subjects. METHODS: In this prospective case series, thirty-six patients with a diagnosis of mild to moderate AD and 36 age-matched control subjects were included. All the subjects underwent neuropsychological (MMSE, ADAS-Cog and CDR) and ophthalmological evaluation, including spectral domain optical coherence tomography (SD-OCT), at baseline and after 12 months. RESULTS: Compared with controls, AD patients had a significant reduction of the total pRNFL thickness, as well as the pRNFL thickness of the inferior and superior quadrants (p=0.04, p=0.001, and p=0.01, respectively, adjusted for baseline pRNFL measurement, age, gender, and axial length). Correlation analysis showed a significant relationship between inferior pRNFL thickness change and ADAS-Cog scores change (r=-0.35, p=0.02) as well as CDR scores at 12 months (r=-0.39, p=0.008). CONCLUSIONS: Compared with controls, AD patients had a significant reduction in pRNFL thickness over a period of 12 months. The pRNFL reduction was more prominent in the inferior quadrant and paralleled patient's cognitive decline. PMID- 27394691 TI - Impact of loaded sit-to-stand exercises at different speeds on the physiological cost of walking in children with spastic diplegia: A single-blind randomized clinical trial. AB - PURPOSE: In the present study, we aimed to determine whether similarly loaded sit to-stand exercises at different speeds improve the physiological cost of walking in children with spastic diplegia. METHODS: This design was a single-blind randomized clinical trial. Sixteen children with cerebral palsy (CP), aged 12-18 years, with a diagnosis of spastic diplegia, were randomly allocated to a slow loaded sit-to-stand exercise group (n=8) and a self-paced loaded sit-to-stand exercise group (n=8). Loaded sit-to-stand exercise was conducted at home for 15min, 4 sets per day, 3-4days per week, for 6 weeks. The patients were evaluated immediately before the intervention and after the training. Lower limb muscle strength using a hand-held dynamometer, selective voluntary motor control using SCALE, 6-min walk distance (6MWD), and Physiological Cost Index (PCI) were measured. RESULTS: The 6MWD showed a significant difference before and after intervention. PCI showed a significant difference between the two groups and the two time points. 6MWD and the PCI improved after intervention in the slow sit-to stand exercise group. CONCLUSIONS: Compared to loaded sit-to-stand exercise at a regular speed, slow low-loaded sit-to-stand exercise improved the 6MWD and PCI in children with CP, suggesting that this decrease in speed during exercise improves the physiological cost of walking in these children. PMID- 27394693 TI - Strand-invading linear probe combined with unmodified PNA. AB - Efficient strand invasion by a linear probe to fluorescently label double stranded DNA has been implemented by employing a probe and unmodified PNA. As a fluorophore, we utilized ethynylperylene. Multiple ethynylperylene residues were incorporated into the DNA probe via a d-threoninol scaffold. The ethynylperylene did not significantly disrupt hybridization with complementary DNA. The linear probe self-quenched in the absence of target DNA and did not hybridize with PNA. A gel-shift assay revealed that linear probe and PNA combination invaded the central region of double-stranded DNA upon heat-shock treatment to form a double duplex. To further suppress the background emission and increase the stability of the probe/DNA duplex, a probe containing anthraquinones as well as ethynylperylene was synthesized. This probe and PNA invader pair detected an internal sequence in a double-stranded DNA with high sensitivity when heat shock treatment was used. The probe and PNA pair was able to invade at the terminus of a long double-stranded DNA at 40 degrees C at 100mM NaCl concentration. PMID- 27394692 TI - Addition of aspirin to a fish oil-rich diet decreases inflammation and atherosclerosis in ApoE-null mice. AB - Aspirin (ASA) is known to alter the production of potent inflammatory lipid mediators, but whether it interacts with omega-3 fatty acids (FAs) from fish oil to affect atherosclerosis has not been determined. The goal was to investigate the impact of a fish oil-enriched diet alone and in combination with ASA on the production of lipid mediators and atherosclerosis. ApoE(-/-) female mice were fed for 13weeks one of the four following diets: omega-3 FA deficient (OD), omega-3 FA rich (OR) (1.8g omega-3 FAs/kg.diet per day), omega-3 FA rich plus ASA (ORA) (0.1g ASA/kg.diet per day) or an omega-3 FA deficient plus ASA (ODA) with supplement levels equivalent to human doses. Plasma lipids, atherosclerosis, markers of inflammation, hepatic gene expression and aortic lipid mediators were determined. Hepatic omega-3 FAs were markedly higher in OR (9.9-fold) and ORA (7 fold) groups. Mice in both OR and ORA groups had 40% less plasma cholesterol in very low-density lipoprotein-cholesterol and low-density lipoprotein fractions, but aortic plaque area formation was only significantly lower in the ORA group (5.5%) compared to the OD group (2.5%). Plasma PCSK9 protein levels were approximately 70% lower in the OR and ORA groups. Proinflammatory aortic lipid mediators were 50%-70% lower in the ODA group than in the OD group and more than 50% lower in the ORA group. In summary, less aortic plaque lesions and aortic proinflammatory lipid mediators were observed in mice on the fish oil diet plus ASA vs. just the fish oil diet. PMID- 27394694 TI - Dose prescription in carbon ion radiotherapy: How to compare two different RBE weighted dose calculation systems. AB - BACKGROUND AND PURPOSE: In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose (DRBE) calculation can lead to deviations in the physical dose (Dphy) delivered to the patient. Our aim is to reduce target Dphy deviations by converting prescription dose values. MATERIAL AND METHODS: Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6Gy (RBE) to 4.6Gy (RBE), according to the Japanese semi-empirical model. The Dphy was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)_I was then applied to estimate DRBE. Target median DRBE ratios between MC+LEM_I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM_I-based commercial system, prescribing the NIRS uncorrected and corrected DRBE. RESULTS: The MC+LEM_I target median DRBE was respectively 15% and 5% higher than the NIRS reference, for the lowest and highest dose levels. Uncorrected DRBE prescription resulted in significantly lower target Dphy in re-optimized plans, with respect to NIRS plans. CONCLUSIONS: Prescription dose conversion factors could minimize target physical dose variations due to the use of different radiobiological models in the calculation of CIRT RBE-weighted dose. PMID- 27394695 TI - Evaluating inter-campus plan consistency using a knowledge based planning model. AB - BACKGROUND AND PURPOSE: We investigate whether knowledge based planning (KBP) can identify systematic variations in intensity modulated radiotherapy (IMRT) plans between multiple campuses of a single institution. MATERIAL AND METHODS: A KBP model was constructed from 58 prior main campus (MC) esophagus IMRT radiotherapy plans and then applied to 172 previous patient plans across MC and 4 regional sites (RS). The KBP model predicts DVH bands for each organ at risk which were compared to the previously planned DVHs for that patient. RESULTS: RS1's plans were the least similar to the model with less heart and stomach sparing, and more variation in liver dose, compared to MC. RS2 produced plans most similar to those expected from the model. RS3 plans displayed more variability from the model prediction but overall, the DVHs were no worse than those of MC. RS4 did not present any statistically significant results due to the small sample size (n=11). CONCLUSIONS: KBP can retrospectively highlight subtle differences in planning practices, even between campuses of the same institution. This information can be used to identify areas needing increased consistency in planning output and subsequently improve consistency and quality of care. PMID- 27394697 TI - Proteomic analysis of ovarian cancer cells during epithelial-mesenchymal transition (EMT) induced by epidermal growth factor (EGF) reveals mechanisms of cell cycle control. AB - : Epithelial to mesenchymal transition (EMT) is a well-orchestrated process that culminates with loss of epithelial phenotype and gain of a mesenchymal and migratory phenotype. EMT enhances cancer cell invasiveness and drug resistance, favoring metastasis. Dysregulation of transcription factors, signaling pathways, miRNAs and growth factors including EGF, TGF-beta and HGF can trigger EMT. In ovarian cancer, overexpression of the EGFR family is associated with more aggressive clinical behavior. Here, the ovarian adenocarcinoma cell line Caov-3 was induced to EMT with EGF in order to identify specific mechanisms controlled by this process. Caov-3 cells induced to EMT were thoroughly validated and a combination of subcellular proteome enrichment, GEL-LC-MS/MS and SILAC strategy allowed consistent proteome identification and quantitation. Protein network analysis of differentially expressed proteins highlighted regulation of metabolism and cell cycle. Activation of relevant signaling pathways, such as PI3K/Akt/mTOR and Ras/Erk MAPK, in response to EGF-induced EMT was validated. Also, EMT did not affected the proliferation rate of Caov-3 cells, but led to cell cycle arrest in G1 phase regulated by increased levels of p21Waf1/Cip1, independently of p53. Furthermore, a decrease in G1 and G2 checkpoint proteins was observed, supporting the involvement of EGF-induced EMT in cell cycle control. BIOLOGICAL SIGNIFICANCE: Cancer is a complex multistep process characterized by accumulation of several hallmarks including epithelial to mesenchymal transition (EMT), which promotes cellular and microenvironmental changes resulting in invasion and migration to distant sites, favoring metastasis. EMT can be triggered by different extracellular stimuli, including growth factors such as EGF. In ovarian cancer, the most lethal gynecological cancer, overexpression of the EGFR family is associated with more aggressive clinical behavior, increasing mortality rate caused by metastasis. Our proteomic data, together with specific validation of specific cellular mechanisms demonstrated that EGF-induced EMT in Caov-3 cells leads to important alterations in metabolic process (protein synthesis) and cell cycle control, supporting the implication of EGF/EMT in cancer metastasis, cancer stem cell generation and, therefore, poor prognosis for the disease. PMID- 27394700 TI - Innate lymphoid cells, precursors and plasticity. AB - Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. PMID- 27394699 TI - Diversity and function of group 1 innate lymphoid cells. AB - Innate lymphoid cells (ILCs) are a heterogeneous population of cells with diverse roles in immune responses. Three major groups of ILCs have been defined on the basis of similarity in their production of signature cytokines, developmental requirements, and phenotypic markers. Group 1 ILCs produce IFN-gamma, express the T-box transcription factors (TF) T-bet and/or Eomesodermin (Eomes), group 2 ILCs secrete IL-5 and IL-13 and express the TF GATA-3, while group 3 ILCs produce IL 22 and IL-17 and express the TF RORgt. In this review, we will briefly overview each group in terms of phenotype, function and development and then focus more extensively on group 1 ILCs, expanding on their emerging diversity, their disparate functions and the differences between NK cells and ILC1. PMID- 27394696 TI - The well-tempered SIV infection: Pathogenesis of SIV infection in natural hosts in the wild, with emphasis on virus transmission and early events post-infection that may contribute to protection from disease progression. AB - African NHPs are infected by over 40 different simian immunodeficiency viruses. These viruses have coevolved with their hosts for long periods of time and, unlike HIV in humans, infection does not generally lead to disease progression. Chronic viral replication is maintained for the natural lifespan of the host, without loss of overall immune function. Lack of disease progression is not correlated with transmission, as SIV infection is highly prevalent in many African NHP species in the wild. The exact mechanisms by which these natural hosts of SIV avoid disease progression are still unclear, but a number of factors might play a role, including: (i) avoidance of microbial translocation from the gut lumen by preventing or repairing damage to the gut epithelium; (ii) control of immune activation and apoptosis following infection; (iii) establishment of an anti-inflammatory response that resolves chronic inflammation; (iv) maintenance of homeostasis of various immune cell populations, including NK cells, monocytes/macrophages, dendritic cells, Tregs, Th17 T-cells, and gammadelta T cells; (v) restriction of CCR5 availability at mucosal sites; (vi) preservation of T-cell function associated with down-regulation of CD4 receptor. Some of these mechanisms might also be involved in protection of natural hosts from mother-to infant SIV transmission during breastfeeding. The difficulty of performing invasive studies in the wild has prohibited investigation of the exact events surrounding transmission in natural hosts. Increased understanding of the mechanisms of SIV transmission in natural hosts, and of the early events post transmission which may contribute to avoidance of disease progression, along with better comprehension of the factors involved in protection from SIV breastfeeding transmission in the natural hosts, could prove invaluable for the development of new prevention strategies for HIV. PMID- 27394698 TI - Interventions for improving coverage of childhood immunisation in low- and middle income countries. AB - BACKGROUND: Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on interventions for improving childhood immunisation coverage in LMICs. OBJECTIVES: To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunisation coverage in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 4, part of The Cochrane Library. www.cochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 12 May 2016); MEDLINE In-Process and Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 12 May 2016); CINAHL 1981 to present, EbscoHost (searched 12 May 2016); Embase 1980 to 2014 Week 34, OvidSP (searched 2 September 2014); LILACS, VHL (searched 2 September 2014); Sociological Abstracts 1952 - current, ProQuest (searched 2 September 2014). We did a citation search for all included studies in Science Citation Index and Social Sciences Citation Index, 1975 to present; Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 2 July 2016). We also searched the two Trials Registries: ICTRP and ClinicalTrials.gov (searched 5 July 2016) SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT), non RCTs, controlled before-after studies, and interrupted time series conducted in LMICs involving children aged from birth to four years, caregivers, and healthcare providers. DATA COLLECTION AND ANALYSIS: We independently screened the search output, reviewed full texts of potentially eligible articles, assessed risk of bias, and extracted data in duplicate; resolving discrepancies by consensus. We then conducted random-effects meta-analyses and used GRADE to assess the certainty of evidence. MAIN RESULTS: Fourteen studies (10 cluster RCTs and four individual RCTs) met our inclusion criteria. These were conducted in Georgia (one study), Ghana (one study), Honduras (one study), India (two studies), Mali (one study), Mexico (one study), Nicaragua (one study), Nepal (one study), Pakistan (four studies), and Zimbabwe (one study). One study had an unclear risk of bias, and 13 had high risk of bias. The interventions evaluated in the studies included community-based health education (three studies), facility-based health education (three studies), household incentives (three studies), regular immunisation outreach sessions (one study), home visits (one study), supportive supervision (one study), information campaigns (one study), and integration of immunisation services with intermittent preventive treatment of malaria (one study).We found moderate-certainty evidence that health education at village meetings or at home probably improves coverage with three doses of diphtheria-tetanus-pertussis vaccines (DTP3: risk ratio (RR) 1.68, 95% confidence interval (CI) 1.09 to 2.59). We also found low-certainty evidence that facility based health education plus redesigned vaccination reminder cards may improve DTP3 coverage (RR 1.50, 95% CI 1.21 to 1.87). Household monetary incentives may have little or no effect on full immunisation coverage (RR 1.05, 95% CI 0.90 to 1.23, low-certainty evidence). Regular immunisation outreach may improve full immunisation coverage (RR 3.09, 95% CI 1.69 to 5.67, low-certainty evidence) which may substantially improve if combined with household incentives (RR 6.66, 95% CI 3.93 to 11.28, low-certainty evidence). Home visits to identify non vaccinated children and refer them to health clinics may improve uptake of three doses of oral polio vaccine (RR 1.22, 95% CI 1.07 to 1.39, low-certainty evidence). There was low-certainty evidence that integration of immunisation with other services may improve DTP3 coverage (RR 1.92, 95% CI 1.42 to 2.59). AUTHORS' CONCLUSIONS: Providing parents and other community members with information on immunisation, health education at facilities in combination with redesigned immunisation reminder cards, regular immunisation outreach with and without household incentives, home visits, and integration of immunisation with other services may improve childhood immunisation coverage in LMIC. Most of the evidence was of low certainty, which implies a high likelihood that the true effect of the interventions will be substantially different. There is thus a need for further well-conducted RCTs to assess the effects of interventions for improving childhood immunisation coverage in LMICs. PMID- 27394701 TI - Serum uric acid concentrations and risk of frailty in older adults. AB - OBJECTIVES: To evaluate for the first time the longitudinal relationship between serum uric acid concentrations and risk of frailty. METHODS: Prospective cohort study of 2198 non-institutionalized individuals aged >=60years recruited in 2008 2010. At baseline, information was obtained on socio-demographic factors, health behaviors and morbidity, while serum uric acid was determined in 12-h fasting blood samples. Study participants were followed-up through 2012 to assess incident frailty, defined as >=2 of the following 4 Fried criteria: exhaustion, muscle weakness, low physical activity, and slow walking speed. RESULTS: During a mean 3.5-year follow-up, 256 cases of incident frailty were identified. After multivariate adjustment, the odds ratios (95% confidence interval) of frailty comparing the second and third tertiles of uric acid to the lowest tertile were, respectively: 1.18 (0.83-1.68) and 1.57 (1.11-2.22); p-linear trend=0.01. The corresponding result for a 1mg/dL increase in serum uric acid concentration was 1.12 (1.00-1.24). Similar associations were observed across subgroups defined by sex, age, body mass index, and physical activity. As regards each frailty component, the odds ratios (95% confidence interval) per 1mg/dL increase in serum uric acid were 1.10 (0.99-1.23) for low physical activity, 1.08 (0.95-1.23) for low walking speed, 1.08 (0.67-1.73) for exhaustion and 0.91 (0.81-1.02) for weakness. CONCLUSIONS: Serum uric acid concentrations are positively associated with the risk of frailty in older adults. Further studies are needed to evaluate whether specific dietary recommendations or pharmacological strategies aimed at lowering serum uric acid would be beneficial to prevent the development of this syndrome. PMID- 27394702 TI - Therapeutic trends and outcome of acromegaly: a single center experience over a 40-year period. AB - OBJECTIVE: To evaluate the therapeutic trends and long-term outcome of treatment modalities for acromegaly in our center over a 40-year period. DESIGN: We retrospectively studied 321 acromegalic patients (145 males/176 females) diagnosed and treated from the 1970s until September 2013. Patients were divided into two subgroups: group A consisted of 166 patients diagnosed before 1990 and group B of 155 patients diagnosed after 1990. Outcome was assessed with GH (random and/or post OGTT) and IGF1 measurements. RESULTS: More group A than group B patients were submitted to radiotherapy (57.8% vs 16.8% patients, respectively, p <0.001). In contrast, more patients of group B were offered surgery (70.3% vs 42.1% in group A, p <0.001) and/or medical treatment (70.3% vs 23.4% in group A, p <0.001). At latest follow-up, 68.4 % of patients in group B achieved GH <2.5 MUg/l after treatment vs 39.8% in group A, p=0.001, 46.9% of patients in group B achieved GH <1 MUg/l vs 20.3% in group A, p=0.001 and 47.1% of patients in group B achieved during OGTT GH nadir <0.4 MUg/l vs 18.6% in group A, p=0.001. CONCLUSIONS: Transsphenoidal resection and medical treatment resulted in improved outcome in acromegalic patients treated over the last 20 years. However, the disease still remains uncontrolled in a considerable number of patients. PMID- 27394703 TI - Low vitamin D status is associated with hypothyroid Hashimoto's thyroiditis. AB - OBJECTIVE: The association of low vitamin D status with autoimmune thyroid disease (AITD), which includes Hashimoto's thyroiditis (HT) and Graves' disease (GD), is controversial. The aim of this study was to investigate the correlation between vitamin D insufficiency and AITD, HT, and GD. DESIGN: Our cross-sectional study included patients who visited a tertiary hospital for thyroid evaluation or follow-up. A total of 776 patients in whom serum 25-hydroxyvitamin D [25(OH)D], thyroid function, and anti-thyroid antibodies had been measured were analyzed retrospectively. Vitamin D insufficiency was defined as serum 25(OH)D level <75 nmol/L. RESULTS: The prevalence of vitamin D insufficiency was significantly higher in the 369 patients with AITD than in the 407 without AITD (46.1% vs. 37.1%, p=0.011), and higher in the 221 patients with HT than in those with GD or non-AITD (48.9% vs. 41.9%, 37.1%, p=0.017). Among HT cases, patients with overt hypothyroidism had a significantly higher prevalence of vitamin D insufficiency (60.4% vs. 44.1%, 21.7%, 37.1%, respectively, p <0.001) and lower 25(OH)D levels (80.1 +/- 47.7 vs. 99.34 +/- 61.2, 110.3 +/- 69.9, 99.6 +/- 53.7 nmol/L, respectively, p=0.009) compared with those with euthyroidism and subclinical hypothyroidism or those without AITD. Serum 25(OH)D levels were significantly negatively correlated with serum thyroid stimulating hormone (TSH) levels after adjustment for age, sex, body mass index, and sampling season (r= -0.127, p=0.013). CONCLUSION: Vitamin D insufficiency was associated with AITD and HT, especially overt hypothyroidism. Low serum vitamin D levels were independently associated with high serum TSH levels. PMID- 27394704 TI - Validity and reliability of the Greek version of the Diabetic Foot Ulcer Scale - Short Form (DFS-SF). AB - OBJECTIVE: Diabetic foot ulcer is a critical and costly complication of diabetes mellitus. The aim of this study was to assess the psychometric properties of the Greek version of the diabetic foot ulcer scale - short form (DFS-SF). DESIGN: A sample of patients with diabetic foot ulcer (N=110) was surveyed with the DFS-SF and various demographic and disease-related questions. The validated Greek SF-36 instrument was used as a "gold standard" for health-related quality of life comparisons. Hypothesized scale structure, internal consistency reliability (Cronbach's alpha) and various forms of construct validity (convergent, discriminative, concurrent and known--groups) were assessed. RESULTS: Multitrait scaling confirmed the scale structure of the DFS-SF, with 32 excellent item convergence (100%) and good discrimination (84.1%) rates. Cronbach's alphawas >0.70 for all scales. Spearman's correlations between similar DFS-SF and SF-36 scales ranged between 0.39-0.79 (p<0.001). Expected interscale correlations and known-groups comparisons supported construct validity. CONCLUSIONS: The observed psychometric properties of the Greek DFS-SF imply suitability for assessing health-related quality of life in patients with diabetic foot ulcer. Future studies should focus on generalizability of the results, as well as on specific issues such as longitudinal validity and responsiveness. PMID- 27394705 TI - Bone mineral status and metabolism in patients with Williams-Beuren syndrome. AB - OBJECTIVE: To evaluate bone mineral status and metabolism in a cohort of patients with Williams-Beuren syndrome (WBS). PATIENTS: Thirty-one children (15 females, 16 males; mean age 9.6+/-2.74 years) and 10 young adults (6 females, 4 males; mean age 21.4+/-5.11 years) with WBS were cross-sectionally evaluated and compared with two age-, sex-, and body-size-matched paediatric (155 subjects, 75 females and 80 males; mean age 9.7+/-2.93 years) and adult (50 subjects, 30 females and 20 males; mean age 22.3+/-5.42 years) healthy controls. MEASUREMENTS: We evaluated ionised and total calcium, phosphate, parathyroid hormone (PTH), 25 hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels, and urinary deoxypyridinoline concentrations. We also calculated the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) z-scores. RESULTS: WBS patients showed a significantly reduced AD-SoS z-score (p <0.001) and BTT z-score (p <0.001) compared with the controls. This finding persisted when we divided the sample into paediatric and adult patients. WBS patients also had significantly higher ionised (p <0.001) and total calcium (p <0.001) levels as well as higher PTH levels (p <0.001) compared with the controls. Furthermore, WBS children and adolescents had significantly lower serum osteocalcin levels (p <0.001) and urinary deoxypyridinoline concentrations (p <0.001) than controls. CONCLUSIONS: WBS subjects exhibit a significant reduction in bone mineral status and impaired bone metabolism. These findings point to the need for close monitoring of WBS patients. PMID- 27394706 TI - Development and validation of an osteoporosis treatment questionnaire (OSTREQ) evaluating physicians' criteria in the choice of treatment. AB - OBJECTIVE: This article describes the development and validation of the osteoporosis treatment questionnaire (OSTREQ), which is a physician-reported outcome tool aiming to evaluate physicians' criteria in the choice of osteoporosis treatment. DESIGN: The questionnaire -named OSTREQ- consisting of 17 questions that were divided into eight sections "Health Care System", "Patients' Preference in administration routes", "Usage, Cost", "Severity of Disease", "Treatment Efficacy", "Safety Profile", "Pharmaceutical Industry", affecting the decision and overall execution of a therapeutic approach, was developed by an expert panel and was later officially translated into English. In the second phase, orthopedic surgeons were asked to complete OSTREQ. Six indirect methods to evaluate validity were adopted: exploratory factor analysis, confirmatory factor analysis, subscale validity, known group validity, floor or ceiling effects, interpretability. To assess the reliability of the questionnaire, internal consistency validity as well as test-retest and parallel forms were calculated. RESULTS: One hundred seventy-two orthopedic surgeons were interviewed with an average period of experience in clinical practice of 10.5 years (SD +/-8.9 years). The factors "Severity of Disease" and "Treatment Efficacy" were the most important in the choice of osteoporosis treatment, while the factor "Pharmaceutical Industry" had the least impact. The methodology of validation proved that the questionnaire possesses construct validity, discriminate ability, reliability, and sensitivity to change. CONCLUSIONS: OSTREQ represents a comprehensive and focused tool that, for the first time, assesses physicians' criteria in the choice of osteoporosis treatment. This tool could assist health care systems and pharmaceutical companies to be aware which parameters drive physicians' preferences regarding osteoporosis treatment. PMID- 27394707 TI - Cabergoline treatment for recurrent Cushing's disease during pregnancy. AB - OBJECTIVE: Cushing's disease during pregnancy is associated with an increased risk for maternal and fetal complications. In recurrent Cushing's disease following transsphenoidal surgery, and when re-operation is not feasible, medical treatment is usually considered. Cabergoline was found to be effective in reducing hypercortisolism in Cushing's disease. Evolving data concerning the safety of cabergoline use during pregnancy show no significant increase in the rate of complications during pregnancy or the postnatal period. METHODS: We report a 29-year-old woman, gravida 0, para 0, with recurrent Cushing's disease, three years after transsphenoidal resection of pituitary ACTH-secreting macroadenoma. Repeated MRI revealed an empty sella with a small gadolinium enhancing lesion, suspected to be an adenoma remnant on the medial wall of the right cavernous sinus. As the patient was not willing to undergo repeat surgical intervention, treatment with cabergoline was initiated, with a gradual dose titration up to 3.5 mg/week. Clinical improvement ensued, and 4 months later, she conceived spontaneously. After discussing treatment options with the patient, cabergoline treatment at a dose of 2 mg/week was continued throughout pregnancy. RESULTS: The patient showed complete clinical remission during pregnancy. Consecutive tests of 24-h urinary free cortisol concentration were not found to be elevated. Pregnancy and delivery were uneventful except for mild hypothyroidism observed during the second trimester. At full term the patient delivered a healthy female infant, by an elective cesarean section. CONCLUSION: This case report demonstrates that cabergoline may be an effective and safe therapeutic option for the treatment of Cushing's disease during pregnancy. PMID- 27394708 TI - A novel MC4R deletion coexisting with FTO and MC1R gene variants, causes severe early onset obesity. AB - OBJECTIVE: Heterozygous mutations on the melanocortin-4-receptor gene (MC4R) are the most frequent cause of monogenic obesity. We describe a novel MC4R deletion in a girl with severe early onset obesity, tall stature, pale skin and red hair. CASE REPORT: Clinical and hormonal parameters were evaluated in a girl born full term by non-consanguineous parents. Her body mass index (BMI) at presentation (3 years) was 30 kg/m2 (z-score: +4.5SDS). By the age of 5.2 years, she exhibited extreme linear growth acceleration and developed hyperinsulinemia. METHODS: Direct sequencing of the MC4R, MC1Rand for the knownFTOsingle nucleotide polymorphism (SNP) rs9939609was performed for the patient and her family. RESULTS: A novel heterozygous MC4R p.Met215del (c.643_645delATG) deletion was identified in the patient, her father and her brother, both of whom exhibited a milder phenotype. 3D structural dynamic simulation studies investigated the conformational changes induced by the p.Met215del. The patient and her mother were also found to be carriers of the obesity risk associated FTOrs9939609SNP. Finally, the identification of the known p.Arg160Trp MC1Rvariant in the patient accounts for the red hair and pale skin phenotypic features. CONCLUSION: The p.Met215del causes global conformational and functional changes as it is localized at the alpha-helical transmembrane regions and the membrane spanning regions of the beta-barrel. This novel mutation produces a severe overgrowth phenotype that is apparent as from infancy and is progressive in childhood. The additional negative effect of environmental and unhealthy lifestyle habits as well as a possible co-interaction of FTOrs9939609 SNP may worsen the phenotype. PMID- 27394709 TI - Cyclopes and Giants: From Homer's Odyssey to contemporary genetic diagnosis. PMID- 27394710 TI - Thyrotoxic hypokalemic periodic paralysis in a Turkish patient presenting with a U wave on ECG. PMID- 27394711 TI - Experimental study on penetration of dental implants into the maxillary sinus at different depths. AB - OBJECTIVE: The purpose of this study was to investigate the effect of the dental implant penetration into the maxillary sinus cavity in different depths on implant and sinus health in a dog model. MATERIALS AND METHODS: The study sample included eight titanium dental implant placed in four female dogs immediately after extraction of the first maxillary molar in the palatal socket and assigned into four groups according to the protruding of implant tips (control group A = 0 mm, and study groups B, C, and D with protrusion of 1, 2, and 3 mm, respectively). The bone blocks of the implants were harvested 5 months postoperatively and evaluated by cone beam computed tomography (CBCT) and histological analysis. RESULTS: The whole groups showed no signs of inflammation during the 5-month period of the study. The tips of the implants in group B with penetrating depths of 1 mm were found to be fully covered with newly formed bone. The tips of the implants in group C with penetrating depths of 2 mm were exposed in the sinus cavity and showed partially new bone coverage, while depths of 3 mm in group D were found to have no bone formation and the dental implant fixture sites were communicated with the sinus cavity. No significant differences were found among the groups regarding implant stability. CONCLUSION: Despite the protrusion extents, penetration of dental implant into the maxillary sinus with membrane perforation does not compromise the sinus health and the implant in canine. PMID- 27394712 TI - Manuscript title: antifungal proteins from moulds: analytical tools and potential application to dry-ripened foods. AB - Moulds growing on the surface of dry-ripened foods contribute to their sensory qualities, but some of them are able to produce mycotoxins that pose a hazard to consumers. Small cysteine-rich antifungal proteins (AFPs) from moulds are highly stable to pH and proteolysis and exhibit a broad inhibition spectrum against filamentous fungi, providing new chances to control hazardous moulds in fermented foods. The analytical tools for characterizing the cellular targets and affected pathways are reviewed. Strategies currently employed to study these mechanisms of action include 'omics' approaches that have come to the forefront in recent years, developing in tandem with genome sequencing of relevant organisms. These techniques contribute to a better understanding of the response of moulds against AFPs, allowing the design of complementary strategies to maximize or overcome the limitations of using AFPs on foods. AFPs alter chitin biosynthesis, and some fungi react inducing cell wall integrity (CWI) pathway. However, moulds able to increase chitin content at the cell wall by increasing proteins in either CWI or calmodulin-calcineurin signalling pathways will resist AFPs. Similarly, AFPs increase the intracellular levels of reactive oxygen species (ROS), and moulds increasing G-protein complex beta subunit CpcB and/or enzymes to efficiently produce glutathione may evade apoptosis. Unknown aspects that need to be addressed include the interaction with mycotoxin production by less sensitive toxigenic moulds. However, significant steps have been taken to encourage the use of AFPs in intermediate-moisture foods, particularly for mould-ripened cheese and meat products. PMID- 27394713 TI - Biology of Paenibacillus larvae, a deadly pathogen of honey bee larvae. AB - The gram-positive bacterium Paenibacillus larvae is the etiological agent of American Foulbrood of honey bees, a notifiable disease in many countries. Hence, P. larvae can be considered as an entomopathogen of considerable relevance in veterinary medicine. P. larvae is a highly specialized pathogen with only one established host, the honey bee larva. No other natural environment supporting germination and proliferation of P. larvae is known. Over the last decade, tremendous progress in the understanding of P. larvae and its interactions with honey bee larvae at a molecular level has been made. In this review, we will present the recent highlights and developments in P. larvae research and discuss the impact of some of the findings in a broader context to demonstrate what we can learn from studying "exotic" pathogens. PMID- 27394715 TI - The in vitro effect of xylitol on chronic rhinosinusitis biofilms. AB - INTRODUCTION: Biofilms have been implicated in chronic rhinosinusitis (CRS) and may explain the limited efficacy of antibiotics. There is a need to find more effective, non-antibiotic based therapies for CRS. This study examines the effects of xylitol on CRS biofilms and planktonic bacteria. METHODS: Crystal violet assay and spectrophotometry were used to quantify the effects of xylitol (5% and 10% solutions) against Staphylococcus epidermidis, Pseudomonas aeruginosa, and Staphylococcus aureus. The disruption of established biofilms, inhibition of biofilm formation and effects on planktonic bacteria growth were investigated and compared to saline and no treatment. RESULTS: Xylitol 5% and 10% significantly reduced biofilm biomass (S. epidermidis), inhibited biofilm formation (S. aureus and P. aeruginosa) and reduced growth of planktonic bacteria (S. epidermidis, S. aureus, and P. aeruginosa). Xylitol 5% inhibited formation of S. epidermidis biofilms more effectively than xylitol 10%. Xylitol 10% reduced S. epidermidis planktonic bacteria more effectively than xylitol 5%. Saline, xylitol 5% and 10% disrupted established biofilms of S. aureus when compared with no treatment. No solution was effective against established P. aeruginosa biofilm. CONCLUSIONS: Xylitol has variable activity against biofilms and planktonic bacteria in vitro and may have therapeutic efficacy in the management of CRS. PMID- 27394714 TI - Cardiac contractility modulation: a novel approach for the treatment of heart failure. AB - Heart failure is a major health problem worldwide and, despite effective therapies, is expected to grow by almost 50 % over the next 15 years. Five-year mortality remains high at 50 % over 5 years. Because of the economic burden and large impact on quality of life, substantial effort has focused on treatments with multiple medical (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB), aldosterone antagonists, and combination of ARB/neprilysin blockers, ivabradine) and device therapies (ICD, CRT) which have been implemented to reduce disease burden and mortality. However, in the past decade only two new medical therapies and no devices have been approved by the US FDA for the treatment of heart failure. This review highlights the preclinical and clinical literature, and the implantation procedure, related to a relatively new therapeutic device for heart failure; cardiac contractility modulation (CCM). CCM delivers a biphasic high-voltage bipolar signal to the RV septum during the absolute refractory period, eliciting an acute increase in global contractility, and chronically producing a sustained improvement in quality of life, exercise tolerance, and heart failure symptoms. The technology is used commercially in Europe with nearly 3000 patients implanted worldwide. Indications include patients with reduced EF and normal or slightly prolonged QRS duration, thus filling an important therapeutic gap among the 2/3 of patients with heart failure who do not meet criteria for CRT. The mechanism by which CCM provides benefit can be seen at the cellular level where improved calcium handling (phosphorylation of phospholamban, upregulation of SERCA-2A), reversal of the fetal myocyte gene program associated with heart failure, and reverse remodeling are observed. Recent retrospective studies indicate a long-term mortality benefit. A pivotal randomized controlled study is currently being completed in the USA. CCM appears to be an effective, safe technology for the treatment of heart failure with reduced ejection fraction. PMID- 27394716 TI - Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study. AB - Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. PMID- 27394718 TI - Performance of Eriopis connexa (Coleoptera: Coccinellidae) resistant to lambda cyhalothrin after extended recovery from knockdown. AB - A population of the predatory lady beetle Eriopis connexa (Germar) (Coleoptera: Coccinellidae) was recorded as resistant to lambda-cyhalothrin. Adults exposed to this insecticide have recovered from knockdown after 72 h. Thus, the performance of resistant (R) and susceptible (S) populations of E. connexa not exposed to insecticide (R0 and S0) and R adults recovering from knockdown 24, 48, and 72 h after exposure (R24, R48, and R72) was studied. In addition, the fertility life table parameters were calculated for one generation considering the progenies from R0, S0, and R24 populations. The recovery rate from knockdown was 69.4% for R-adults, and greater recovery rate was observed within 48 h following lambda cyhalothrin exposure. The S-females produced about 50% more eggs and lived longer, when compared with R-females irrespective of the recovery periods after knockdown. The R-females produced similar number of eggs and exhibited similar longevity across all treatments (R0, R24, R48, and R72). Progenies produced by R- and S-populations did not exhibit consistent differences in development and survival. The fertility life table parameters showed higher intrinsic rate of population growth (rm) and lower mean generation time (T) for R0- and R24 females, when compared with those for S0-females. Thus, the time interval needed to recover from knockdown is not related to the adaptive cost of resistance in E. connexa. PMID- 27394717 TI - Evaluation of biomarkers assessing regular alcohol consumption in an occupational setting. AB - PURPOSE: An estimation of ethanol intake is frequently of importance in the frame work of studies, but not trivial to achieve. Problems are "underreporting", a very short time frame for the detection of ethanol as direct marker and interference of many in- and outside body factors with strain parameters. The aim of this study was to explore the suitability of the direct urinary biomarkers ethyl glucuronide (EtG) and ethyl sulphate (EtS) to assess moderate but regular alcohol consumption. MATERIALS AND METHODS: A total of 175 male workers without any known occupational contact to substances influencing liver functions or metabolism of ethanol were examined. Strain parameters of alcohol consumption, i.e. the liver function tests (LFTs: aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase), carbohydrate-deficient transferrin (CDT), mean corpuscular erythrocyte volume (MCV) and the markers of alcohol consumption (EtG and EtS) have been analysed and compared. RESULTS: Up to 14 % of workers had been outside reference range for strain parameters. 62.3 % of the workers had at least traceable amounts of EtG and 84.6 % of EtS. Values above cut off (indicating voluntary ethanol intake) were found in 34.9 and 51.4 % of the workers for EtG and EtS, respectively. In multiple linear regression analyses, CDT and MCV but not the LFTs showed a dependency from the non-oxidative ethanol metabolites. The LFTs were influenced by BMI. CONCLUSION: Determination of EtG and EtS in urine is an adequate tool to assess moderate but regular alcohol consumption. PMID- 27394719 TI - Associations Between Macroinvertebrates and Paralemanea mexicana, an Endemic Freshwater Red Alga from a Mountain River in Central Mexico. AB - Macrophytes are common inhabitants of lotic environments and, depending on their morphological traits, possess adaptations that provide shelter to aquatic invertebrates against strong river flow and predators. They may also be used as a food source by macroinvertebrates. The main goal of this study was to determine the relationship between the red alga Paralemanea mexicana and its role as a shelter and/or food source for lotic macroinvertebrates. We also conducted research on the role of microhabitat and morphological variations of the alga in determining macroinvertebrate taxon abundance, diversity, and functional group composition in a high-current velocity river. Results showed that changes in cover and morphology of P. mexicana were mostly correlated with river current velocity, irradiance, and seasonal variation. In turn, these were related to changes in abundance and diversity of the associated macroinvertebrate community. In addition, six macroinvertebrate functional feeding groups were evaluated for associations with the red alga: filtering and gathering collectors, piercers, scrapers, herbivore shredders, and predators. The results showed that the Trichoptera Hydroptilidae genera Ochrotrichia and Metrichia use P. mexicana as a food source and case-building material. The Trichoptera Glossosomatidae Mortoniella uses the alga as a substrate. The biotic interactions between P. mexicana and associated macroinvertebrates reveal the importance of macrophytes as purveyors of substrate, as food and shelter for macroinvertebrates, and also as promoters of macroinvertebrate community diversity. In addition, it was shown that macroinvertebrate herbivory likely facilitates vegetative propagation of the red alga through increased release and germination of carpospores and new gametophytes. PMID- 27394720 TI - Regulatory Innovation, Mating Disruption and 4-Play(TM) in New Zealand. AB - Straight-chained lepidopteran pheromones are now regulated under a group standard in New Zealand, which is generic for moth pheromone products of similar low risk, under the Hazardous Substances and New Organisms Act (1996). This means that compliant new pheromone products can be developed and commercialized with low regulatory requirements. This encourages innovation and supports fruit industries interested in meeting export phytosanitary standards, while targeting low or nil residues of pesticides. Changes to pheromone blends for reasons such as technical improvements or variations in pest species composition in different crops can be made with minimal regulatory involvement. We illustrate how this system now operates with a four species mating disruption product commercialized in 2012. The odors involved in "4-PlayTM" consist of a range of components used by codling moth (Cydia pomonella), lightbrown apple moth (Epiphyas postvittana), green headed leafroller (Planotortrix octo), and brown-headed leafroller (Ctenopseustis obliquana). The development of 4-PlayTM illustrates how mating disruption of insects can support industry goals. PMID- 27394721 TI - FoxP1 Protein Shows Differential Layer Expression in the Parahippocampal Domain among Bird Species. AB - Different bird orders show diversity in neural capabilities supported by variations in brain morphology. The parahippocampal domain in the medial pallium, together with the hippocampus proper, plays an important role in memory skills. In the present work, we analyze the expression pattern of the FoxP1 protein in the parahippocampal area of four different bird species: the nonvocal learner birds quail and chicken (Galliformes) and two vocal learner birds, i.e. the zebra finch (Passeriformes) and the budgerigar (Psittaciformes), at different developmental and adult stages. We also analyze the expression of the calbindin protein in quails and zebra finches. We observed differences in the FoxP1 parahippocampal layer among bird species. In quails, chickens, and budgerigar, FoxP1 cells were located in the outer layers of the lateral and caudolateral parahippocampal sectors. In contrast, FoxP1 immunoreactive cells appeared in the inner layer of the same sectors in the zebra finch parahippocampal domain. These differences suggest two possibilities: either the FoxP1-positive cells described in quails, chickens, and budgerigars are a different population than the one described in the zebra finch, or there are changes in the pattern of radial migration in the parahippocampal area among birds. In the present study, we show that FoxP1 expression is more similar between quails, chickens, and budgerigars than between budgerigars and zebra finches in the parahippocampal area. This result contrasts with previous data in other telencephalic structures, like the calbindin-positive projection neurons described in the striatum of budgerigars and zebra finches but not in quails and chickens. All of these data point to diversity in the evolution of different morphological characters and, therefore, a mosaic model for telencephalic evolution in birds. PMID- 27394723 TI - Inadequate Macronutrient and Micronutrient Intakes in Hemodialysis and Peritoneal Dialysis Patients: Data from a Seven-Day Weighed Dietary Record. AB - BACKGROUND/AIMS: It is very important to assess the nutritional intake in patients on dialysis given the high prevalence of poor nutritional status of those in this population. The aim of this study was to assess nutrient intakes in hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: A clinical cross-sectional study was conducted over 7 days on 14 dialysis patients (98 days) who were trained to keep a weighed food record and a 7-day food diary. Nutrient intake adequacy was compared with specific guidelines for Italians and dialysis patients. RESULTS: The mean daily protein intake (0.92 +/- 0.36 g/kg) and energy intake (EI; 25.3 +/- 7.4 kcal/kg) were inadequate according to the European best practice guidelines (EBPG). The ratio of EI to resting energy expenditure was 1.22. Inadequate intakes, compared to the EBPG, were found for calcium (525 +/- 162 mg/day) and iron (8.7 +/- 2.1 mg/day). Dietary fiber (14.7 +/- 8.7 g/day), niacin (14.4 +/- 5.2 mg/day), thiamine (0.8 +/- 0.3 mg/day) and riboflavin (1.1 +/- 0.4 mg/day) were also inadequate according to the Italian recommended dietary allowances (LARN). HD patients did not display different nutrient intakes between the dialysis days and the interdialytic period. Overall, the percentage of days during which nutrient recommendations were not satisfied ranged from 16 to 100% depending on the nutrient. CONCLUSION: Macronutrient and micronutrient intakes in HD and PD patients are largely inadequate compared to the EBPG. The weighed dietary record appears to be a useful and accurate tool for individual assessment of food intake in motivated patients. No nutrient intake differences were found between dialytic and interdialytic days in patients on HD. PMID- 27394725 TI - Backbone and side chain assignments of human cell cycle regulatory protein S phase kinase-associated protein 1. AB - Ubiquitination of proteins is required to regulate several cellular mechanisms in cells. Skp1-Cullin-1-F-box (SCF), the largest family of the RING E3 ligases, recognizes and carries out the poly-ubiquitination of many substrate proteins. SCF E3 ligase is a multi-component protein complex, and the human S-phase kinase associated protein 1 (Skp1) is the adapter protein, which binds and presents the substrate binding protein F-box (FBP) to the rest of the E3 ligase. Several crystallographic studies have solved the partial structure of Skp1 in complex with various FBPs, but there is no structure of standalone Skp1. Understanding the conformational and structural properties of Skp1 with and without FBPs is required to understand the complete mechanism of poly-ubiquitination. Here, we report ~90 % backbone and 64 % side chain (1)H, (13)C, (15)N assignments of Skp1 protein using various double and triple resonance NMR experiments. PMID- 27394724 TI - Feedback control indirect response models. AB - A general framework is introduced for modeling pharmacodynamic processes that are subject to autoregulation, which combines the indirect response (IDR) model approach with methods from classical feedback control of engineered systems. The canonical IDR models are modified to incorporate linear combinations of feedback control terms related to the time course of the difference (the error signal) between the pharmacodynamic response and its basal value. Following the well established approach of traditional engineering control theory, the proposed feedback control indirect response models incorporate terms proportional to the error signal itself, the integral of the error signal, the derivative of the error signal or combinations thereof. Simulations are presented to illustrate the types of responses produced by the proposed feedback control indirect response model framework, and to illustrate comparisons with other PK/PD modeling approaches incorporating feedback. In addition, four examples from literature are used to illustrate the implementation and applicability of the proposed feedback control framework. The examples reflect each of the four mechanisms of drug action as modeled by each of the four canonical IDR models and include: selective serotonin reuptake inhibitors and extracellular serotonin; histamine H2-receptor antagonists and gastric acid; growth hormone secretagogues and circulating growth hormone; beta2-selective adrenergic agonists and potassium. The proposed feedback control indirect response approach may serve as an exploratory modeling tool and may provide a bridge for development of more mechanistic systems pharmacology models. PMID- 27394722 TI - Effects of dorsolateral prefrontal cortex lesion on motor habit and performance assessed with manual grasping and control of force in macaque monkeys. AB - In the context of an autologous adult neural cell ecosystem (ANCE) transplantation study, four intact adult female macaque monkeys underwent a unilateral biopsy of the dorsolateral prefrontal cortex (dlPFC) to provide the cellular material needed to obtain the ANCE. Monkeys were previously trained to perform quantitative motor (manual dexterity) tasks, namely, the "modified Brinkman board" task and the "reach and grasp drawer" task. The aim of the present study was to extend preliminary data on the role of the prefrontal cortex in motor habit and test the hypothesis that dlPFC contributes to predict the grip force required when a precise level of force to be generated is known beforehand. As expected for a small dlPFC biopsy, neither the motor performance (score) nor the spatiotemporal motor sequences were affected in the "modified-Brinkman board" task, whereas significant changes (mainly decreases) in the maximal grip force (force applied on the drawer knob) were observed in the "reach and grasp drawer" task. The present data in the macaque monkey related to the prediction of grip force are well in line with the previous fMRI data reported for human subjects. Moreover, the ANCE transplantation strategy (in the case of stroke or Parkinson's disease) based on biopsy in dlPFC does not generate unwanted motor consequences, at least as far as motor habit and motor performance are concerned in the context of a sequential grasping a small objects, which does not require the development of significant force levels. PMID- 27394726 TI - (1)H, (13)C and (15)N backbone resonance assignments and dynamic properties of the PDZ tandem of Whirlin. AB - Mammals perceive sounds thanks to mechanosensory hair cells located in the inner ear. The stereocilia of these cells are tightly bound together in bundles by a network of cadherins and scaffolding proteins. Stereocilia deflection induces stretching of this network and is responsible for hair cell depolarization that triggers the neuronal message, transducing the mechanical signal into an electric signal transmissible to the brain. Nearly all proteins involved in this mechano electrical transduction network contain short C-terminal motifs of interaction with PDZ domains (PSD-95, Discs Large, ZO-1). Interestingly only two of these proteins encompass PDZ domains: Harmonin and Whirlin. As our first step towards a comprehensive structural study of Whirlin, we have assigned the (1)H, (13)C and (15)N backbone resonances of a tandem formed by the first two PDZ domains of Whirlin, reported the secondary structure elements of this tandem as predicted by the TALOS+ server and evaluated its dynamics from (15)N relaxation measurements. PMID- 27394727 TI - Codon Optimization of the "Bos Taurus Chymosin" Gene for the Production of Recombinant Chymosin in Pichia pastoris. AB - Codon optimization of the Bos taurus Chymosin gene (CYM) for its expression in Pichia pastoris was performed in this study. A synthetic CYM gene was designed in silico by replacing codons rarely used by P. pastoris with equivalent nucleotide combinations that codify for the same amino acid but that are more frequently encountered in the genome of P. pastoris. A total of 332 nucleotides were modified to optimize 289 codons. The synthetic CYM gene was cloned into the expression vector pPICZalphaA and transformed into P. pastoris. The transformed strains were grown in artificial media supplemented with glycerol as a carbon source to increase biomass and then cultured in a similar medium replacing glycerol with methanol as a carbon source to initiate gene induction. Raw extracts of the growth media exhibited milk-clotting activity of 146.11 SU/mL. Produced recombinant chymosin showed coagulant activity from 25 to 50 degrees C, and within a pH range of 5-6.9, having optimum activity at 35-40 degrees C, and pH 5.0. These results show that codon optimization is a viable strategy to improve CYM gene expression levels in P. pastoris for the production of recombinant chymosin. PMID- 27394728 TI - Dose reduction technique in diagnostic X-ray computed tomography by use of 6 channel multileaf collimators. AB - Recently, region-setting computed tomography (CT) has been studied as a region of interest imaging method. This technique can strongly reduce the radiation dose by limiting the irradiation field. Although mathematical studies have been performed for reduction of the truncation artifact, no experimental studies have been performed so far. In this study, we developed a three-dimensional region-setting CT system and evaluated its imaging properties. As an experimental system, we developed an X-ray CT system with multileaf collimators. In this system, truncated projection data can be captured by limiting of the radiation field. In addition, a truncated projection data correction was performed. Finally, image reconstruction was performed by use of the Feldkamp-Davis-Kress algorithm. In the experiments, the line profiles and the image quality of the reconstructed images were evaluated. The results suggested that the image quality of the proposed method is comparable to that of the original method. Furthermore, we confirmed that the radiation dose was reduced when this system was used. These results indicate that a 3D region-setting CT system using 6-channel multileaf collimators can reduce the radiation dose without in causing a degradation of image quality. PMID- 27394729 TI - Revision of the Japanese species of Trichoclinocera Collin (Diptera: Empididae: Clinocerinae). AB - The Japanese species of Trichoclinocera are revised and include nine species, of which seven are new species (T. dasy-scutellum (Saigusa), T. fuscipennis Saigusa, T. gracilis sp. nov., T. grandis sp. nov., T. miranda sp. nov., T. setigera sp. nov., T. shinogii sp. nov., T. stigmatica sp. nov., T. takagii sp. nov.). A key to all nine species is provided, their distributions mapped and affinities discussed. PMID- 27394730 TI - Nicola gen. nov. with redescription of Nicola tetela (Borojevic & Peixinho, 1976) (Porifera: Calcarea: Calcinea: Clathrinida). AB - Guancha tetela was originally described as a species having a peduncle and a skeleton exclusively composed of sagittal triactines. Therefore, according to the most recent phylogeny of Clathrinida, it should be placed in the genus Clathrina. This species was collected on the Northeastern Brazilian coast in 1968 and it was not collected again until 2011 in Curacao. In this study, we reanalyzed the type material and the new specimens from Curacao under a morphological-molecular approach. Morphological analysis revealed the presence of tetractines in the skeleton of all the studied specimens, including a slide of the holotype. In the molecular phylogeny G. tetela grouped with genera containing tetractines, but as an independent new lineage, different from all the other genera of Clathrinida. Based on these results, we propose the erection of a new genus, Nicola gen. nov., to include species whose body is composed of tubes without anastomosis nor branches but that run in parallel and coalesce at the apical and basal regions. Moreover, the skeleton is exclusively composed of sagittal triactines and tetractines. PMID- 27394731 TI - A review of the fleas (Insecta: Siphonaptera) from Argentina. AB - The Order Siphonaptera comprises cosmopolitan haematophagous ectoparasites of birds and mammals. More than ten years have past since the last list of species known for Argentina. Herein we provide a review of the fleas from the country, which includes an updated list, host species and geographical distribution for each taxa, as well as some comments. We report 127 species and subspecies belonging to eleven different families; 42 of these species are endemic. Four genera (Adoratopsylla, Cleopsylla, Ctenidiosomus, and Nonnapsylla) and six species and subspecies (Adoratopsylla (Adoratopsylla) antiquorum antiquorum, Agastopsylla pearsoni, Polygenis (Polygenis) roberti beebei, Plocopsylla (Plocopsylla) silewi, Plocopsylla (Plocopsylla) wilesi and Tunga terasma) are added to the list for Argentina. Nine species new to science are included, described on the bases of specimens collected from Argentina (Ctenidiosomus austrinus, Ectinorus (Ectinorus) lareschiae, Ectinorus (Ectinorus) spiculatus, Ectinorus (Ectinorus) morenoi, Hectopsylla narium, Plocopsylla (Plocopsylla) linardii, Neotyphloceras crackensis, Neotyphloceras pardinasii and Tunga perforans). Information provided herein contributes to the knowledge of the fleas from Argentina, necessary to a better understanding of their role as parasites themselves and vectors of zoonotic importance. PMID- 27394732 TI - Two new species of the genus Hishimonus (Hemiptera: Cicadellidae) with a new record from India. AB - Two new species of leafhoppers, Hishimonus nauniensis sp. nov. (from Himachal Pradesh: Solan) and Hishimonus pantanagarensis sp. nov. (from Uttarakhand: Pant Nagar) from India, are described and illustrated. Also, the species Hishimonus thapai Virakatamath and Mohan, previously known only from Nepal is illustrated with a new record for India. PMID- 27394733 TI - New records of five sponge species (Porifera) for the Black Sea. AB - The present study deals with five sponge species [Chalinula renieroides, Haliclona (Halichoclona) fulva, H. (Rhizoniera) rosea, Hymedesmia (Hymedesmia) pansa and Ircinia variabilis] belonging to 3 families (Chalinidae, Hymedesmiidae, and Irciniidae) found at one locality (near the opening of Kizilirmak River) on the Black Sea coast of Turkey. All these species are new records for the Black Sea. Three species (Chalinula renieroides, H. (R.) rosea and H. (H.) pansa] are also new records for the marine fauna of Turkey. All these species were previously reported from Mediterranean Sea and the eastern Atlantic Ocean. The morphological and distributional features of these species are presented. PMID- 27394734 TI - Description of Myolepta pazukii Gilasian & Reemer sp. nov. (Diptera: Syrphidae) with notes on the Iranian species of Myolepta Newman. AB - Myolepta pazukii Gilasian & Reemer sp. nov. is described from Iran based on a single male specimen. Photographs of the male holotype and illustrations of its abdomen and hypandrium are provided. The new species is incorporated into the key to the west Palaearctic Myolepta species provided by Reemer et al. (2004). Taxonomic notes and distribution data on two recorded Iranian Myolepta species are presented. PMID- 27394735 TI - Recognition of the genus Habrocampulum Gauld, 1976 (Hymenoptera: Ichneumonidae: Anomaloninae) from Japan, with a new combination and a key to the species. AB - Recognition of the genus Habrocampulum Gauld, 1976 (Hymenoptera:Ichneumonidae: Anomaloninae) from Japan, with a new combination and a key to the species. PMID- 27394736 TI - First record of the genus Pion Schiodte, 1839 (Hymenoptera: Ichneumonidae: Ctenopelmatinae), from Japan, with description of a new species. AB - The genus Pion Schiodte, 1839, is newly recorded from Japan based on a new species, P. japonicum sp. nov. This species closely resembles the Chinese species P. qinyuanensis Chen, Sheng & Mao, 1998, but it can be distinguished from the following combination of character states (male of P. qinyuanensis is unknown): lateromedian longitudinal carina of propodeum completely parallel, not convergent anteriorly (almost parallel but slightly convergent anteriorly in P. qinyuanensis); malar space 0.6 times as long as basal width of mandible (0.5 times in P. qinyuanensis); antenna with 28-29 flagellomeres (30-34 in P. qinyuanensis); hind femur black, rarely tinged with red (largely red in P. qinyuanensis); and hind tibia yellowish-brown basally, black apically (entirely black in P. qinyuanensis). A key to world species of Pion is also provided. PMID- 27394737 TI - Bolboceras bilaspuricans (Coleoptera: Geotrupidae: Bolboceratinae), a new species from Chhattisgarh, India. AB - Bolboceras bilaspuricans Gupta & Chandra, new species (Coleoptera: Geotrupidae: Bolboceratinae), from the Chhattisgarh state, India is described, diagnosed, and illustrated. The new species is classified in the B. nigricans species group of the genus Bolboceras Kirby, 1819. The new species is morphological similar to Bolboceras malabaricum Krikken, 2013 from southwestern India. PMID- 27394738 TI - New genera and species of the minute snakeflies (Raphidioptera: Mesoraphidiidae: Nanoraphidiini) from the mid Cretaceous of Myanmar. AB - The Mesozoic amber snakeflies are important for understanding the early evolution and phylogeny of Raphidioptera. Here we describe three new genera and four new species of the extinct family Mesoraphidiidae from the mid Cretaceous amber of northern Myanmar, including Dolichoraphidia aspoecki gen. et sp. nov., Dolichoraphidia engeli gen. et sp. nov., Rhynchoraphidia burmana gen. et sp. nov., and Burmoraphidia reni gen. et sp. nov. All these species, together with the previously described species (i.e., Nanoraphidia electroburmica Engel, 2002) from Burmese amber, belong to the mesoraphidiid tribe Nanoraphidiini based on the minute body-size and the swollen tibiae. A key to all species of Nanoraphidiini is provided. A brief discussion on the genital morphology of Mesoraphidiidae is also given. PMID- 27394739 TI - Taxonomic remarks on the genus Ctenodrilus (Annelida: Cirratulidae) including description of a new species from the Pacific Ocean. AB - A new species of Ctenodrilus is described based on morphology, anatomy and molecular (COI and 16S) data. Phylogenetic analyses revealed that the newly described Hawaiian species is the sister taxon of the widely distributed C. serratus. Comparisons of K2P distances show distances of at least 10.9 % for 16S and 18.7 % for CO1. Morphology of C. serratus differs from C. pacificus sp. nov. in the shape, number and distribution of multidentate hooks along the body, extent in segments of anterior ventral cilia, and presence of stomach cilia. Ctenodrilus pacificus sp. nov. resembles C. parvulus in terms of the internal anatomy but differs in respect to the shape of multidentate hooks. Asexual reproduction in the new species is described including associated changes in the external morphology and internal anatomy. A revision of the taxonomic characters of Ctenodrilus is also presented in order to provide background information for a better assessment of the widely distributed taxon Ctenodrilus serratus. PMID- 27394740 TI - Eremobiotus ginevrae sp. nov. and Paramacrobiotus pius sp. nov., two new species of Eutardigrada. AB - Two new eutardigrade species are described: Eremobiotus ginevrae sp. nov. and Paramacrobiotus pius sp. nov. The first is similar to Eremobiotus alicatai (Binda, 1969) but differs in the claw shape and dimensions. It has been found in Sicily, Israel and Russia. The second species, belonging to the richtersi group, is currently found exclusively in Sicily. It has a smooth cuticle, three macroplacoids and a microplacoid, eggs with reticulated trunco-conical processes with small terminal thorns; the egg-shell is areolated and the areolae are clearly sculptured. PMID- 27394741 TI - Identification of three morphologically indistinguishable Epicauta species (Coleoptera, Meloidae, Epicautini) through DNA barcodes and morphological comparisons. AB - Three species that belong to the genus Epicauta (Coleopera: Meloidae), E. chinensis, E. dubia, and E. sibirica, appear morphologically indistinguishable. The present study aims to resolve the taxonomic status and the relationships among these three species. Identifying adult morphological characters among the three species were compared and illustrated and partial fragments of the mitochondrial gene (COI) for 77 samples, representing seven meloid species, were obtained and analyzed. Analyses of nucleotide composition, genetic distances and phylogenetics were performed. The results of the morphological studies and molecular analyses showed concordance, indicating that the three species are closely related and indistinguishable from one another. Consequently, two new synonyms are proposed: E. chinensis (Laporte, 1840) syn. n. = E. sibirica (Pallas, 1773) and E. dubia (Fabricius, 1781) syn. n. = E. sibirica (Pallas, 1773). PMID- 27394742 TI - New African species of Helina Robineau-Desvoidy (Diptera, Muscidae). AB - The study of Afrotropical Muscidae deposited in the Natural History Museum (BMNH), London, United Kingdom, revealed four new species of Helina Robineau Desvoidy, herein described and illustrated. Helina duocolorata sp. nov. is described from Kenya, Helina longicerca sp. nov. and Helina sexnotata sp. nov. from Nigeria, and Helina mediomaculata sp. nov. from Angola. All types are deposited in the collection of the BMNH. Some corrections are made to the entries under Helina in the Catalogue of the Diptera of the Afrotropical Region (Pont 1980). PMID- 27394743 TI - Chilocoris serratus n. sp., the first burrower bug species (Hemiptera: Heteroptera: Cydnidae) recorded in Guinea-Bissau with an annotated checklist of the Afrotropical species of the genus Chilocoris Mayr, 1865. AB - The first burrower bug species recorded in Guinea-Bissau, Chilocoris serratus n. sp., is described and compared with morphologically related species. Additionally, an annotated checklist of Afrotropical species of the genus Chilocoris is provided. PMID- 27394744 TI - Telosticta fugispinosa sp. nov. from Sabah (Odonata: Zygoptera: Platystictidae). AB - Telosticta fugispinosa sp. nov. (holotype male, from Borneo, Sabah, West Coast division, Crocker Range National Park, Inobong, Kimamabang waterfall stream system, 21 ix 2012, deposited in RMNH) is described from Kinabalu National Park and Crocker Range National Park in Sabah, Malaysian Borneo. It is distinguished from all other species of Telosticta by the form of the male anal appendages. PMID- 27394745 TI - Would Nesotriatoma bruneri Usinger, 1944 be a valid species? AB - Variation in the size and morphological differences intraspecific of Nesotriatoma flavida led to the description of N. bruneri. However, two years later the same author proposed the synonymization N. bruneri with N. flavida. N. bruneri was revalidated through morphological analysis after 35 years. Thus, given the existing taxonomic questioning between these Cuban triatomines, we analyzed new parameters such as genetic distance from the mitochondrial 16S rDNA deposited in Genbank and cytogenetic characterization, through the constitutive heterochromatin pattern, in order to reassess the specific status of N. bruneri. The analysis of the disposition of constitutive heterochromatin in the genome of these triatomines allowed observing that only the sex chromosome Y is heterochromatic, and the autosomes and the sex chromosomes X are euchromatic. These characteristics are identical to those described for N. flavida. By means of analysis of genetic distance matrix, we found that the genetic distance between N. bruneri and N. flavida was only 0.04%. Thus, by means of extremely low genetic distance and identical cytogenetic characteristics, we suggest that N. bruneri should be back again synonymized with N. flavida. However, we recommend that experimental hybrid crosses and new molecular analysis should be conducted, focusing mainly in the genetic distance based on other genes, on the rate of fertility of eggs and viability of hybrids to confirm the proposed of synonymization. PMID- 27394746 TI - Revision of the Amazonian species of Syneches Walker (Diptera, Hybotidae, Hybotinae). AB - A revision of the Amazonian species of Syneches Walker resulted in the re description of four species and the description of nine new species: Syneches amazonicus sp. nov., S. angulatus sp. nov., S. applanatus sp. nov., S. bilobatus sp. nov., S. equatoriensis sp. nov., S. exilis sp. nov., S. maculosum sp. nov., S. striatus sp. nov., S. tenebricus sp. nov., and two new synonymies: S. quadricinctus (Fabricius, 1805) = S. curvipes (Fabricius, 1805) and S. hispidus Ale-Rocha & Vieira, 2008 = S. repletus Bezzi, 1909. The male of S. fuscescens Bezzi and the female of S. annulipes Bezzi are described and their terminalia are illustrated. Geographic records for S. annulipes Bezzi, S. curvipes (Fabricius), S. fuscescens Bezzi, S. manaos Smith, S. moraballi Smith, S. rafaeli Ale-Rocha & Vieira, S. repletus Bezzi and S. walkeri Smith and an identification key for the species recorded in the Amazon are provided. PMID- 27394747 TI - Description of three new species of Glyphepomis Berg (Heteroptera: Pentatomidae: Pentatominae). AB - Three new species of the Glyphepomis are described: Glyphepomis dubia Campos & Souza, sp. nov., Glyphepomis amazonica Goncalves & Campos, sp. nov. and Glyphepomis magnocephala Bianchi & Campos, sp. nov. Comparative illustrations of external and internal genitalia, distribution map of the described species, additions to the genus description, and a key to the species are provided. PMID- 27394748 TI - Description of two new species of the Lethe manzorum-group (Lepidoptera, Nymphalidae, Satyrinae) from China. AB - The Lethe manzorum-group is studied and two new species (L. sisii sp. nov. and L. giancbozanoi sp. nov.) closely related to L. manzorum (Poujade, 1884) from China are described and illustrated. PMID- 27394749 TI - Taxonomy of 'Euconnus complex'. Part VIII. Subgenera Napoconnus, Himaloconnus and Nepaloconnus removed from Euconnus
(Coleoptera, Staphylinidae, Scydmaeninae). AB - Examination of the type species of Napoconnus, Himaloconnus and Nepaloconnus, taxa previously placed as subgenera of Euconnus, revealed characters remarkably different from those diagnostic for Euconnus. Napoconnus and Himaloconnus have narrowly separated metacoxae, with the metaventral intercoxal process bearing a pair of long and pointed spines touching at middle; this character alone excludes these taxa from Euconnus. Consequently, Napoconnus and Himaloconnus are elevated to the genus rank and redefined. Nepaloconnus was clearly defined on the basis of misinterpreted characters and this name is placed as a junior synonym of Microscydmus s. str. (resulting in Microscydmus khumbuensis (Franz) comb. n.). Morphological structures of the treated species are described and illustrated and taxonomic problems related to the large 'Euconnus complex' are discussed. PMID- 27394750 TI - Description of two new species of the genus Atlanticus from Southern China and their songs (Orthoptera: Tettigoniidae; Tettigoniinae). AB - Two new species Atlanticus (Sinpacificus) jiangyei sp. n. and Atlanticus (Sinpacificus) helleri sp. n. are described, based on morphology and male calling songs. Based on the morphological characters, the closest relative of Atlanticus (Sinpacificus) jiangyei sp. n. and that of Atlanticus (Sinpacificus) helleri sp. n. are separately assumed to be Atlanticus (Sinpacificus) hangfui Liu, and Atlanticus (Sinpacificus) kiangsui Tinkham. Discussion about characteristics of Atlanticus species is also provided. PMID- 27394751 TI - A remarkable new species of Coeliccia from the Tuyen Lam Lake area, Lam Dong, southern Vietnam (Odonata: Zygoptera: Platycnemididae). AB - Coeliccia suoitia sp. nov. (holotype ?, from Suoi Tia, Tuyen Lam Lake, Da Lat, Lam Dong Province, Vietnam, deposited in RMNH) is described from males from southern Vietnam. It is a distinctive species that possess highly unusual characters in the thorax and anal appendages that make its ultimate generic placement questionable. Relationships between Coeliccia Kirby, Asthenocnemis Lieftinck and Indocnemis Laidlaw, and within Coeliccia, are briefly discussed. PMID- 27394752 TI - New data on poorly known species of the genus Leia Meigen (Diptera, Mycetophilidae) from the Palaearctic region. AB - New data on four poorly known species of the genus Leia Meigen (L. nigricornis van Duzee, L. flavipennis Lastovka & Matile, L. iturupensis Zaitzev and L. rufiptera Ostroverkhova) are presented. Detailed redescriptions and terminalia figures are provided. Leia nigricornis is reported for the first time from the Palaearctic region and L. automnala Ostroverkhova & Grishina is found to be a junior synonym of L. flavipennis. A variation in the male terminalia of L. bimaculata Meigen is illustrated, based on specimens from several European countries. PMID- 27394753 TI - Coenosia Meigen (Diptera: Muscidae) from Angola: new species and records. AB - The study of unidentified material from Angola (Africa), deposited in the collection of the Natural History Museum, London, United Kingdom, has revealed three new Coenosia species: Coenosia lucens sp. nov., Coenosia flavohumeralis sp. nov. and Coenosia setosa sp. nov., and five new records: Coenosia macrochaeta (Emden, 1940), Coenosia nodosa Stein, 1913, Coenosia ochroprocta (Speiser, 1910), Coenosia planifrons Stein, 1913 and Coenosia translucida (Emden, 1940). Only one species of Coenosia had previously been recorded from Angola: Coenosia sanguenguei Zielke 1971. The new species are described with illustrations of the male terminalia, and diagnoses of the newly-recorded species with descriptions of the male terminalia are given. A list of all Muscidae species recorded from Angola is presented. PMID- 27394754 TI - The New World Gibbobruchus Pic (Coleoptera, Chrysomelidae, Bruchinae): description of a new species and phylogenetic insights into the evolution of host associations and biogeography. AB - The seed beetle Gibbobruchus tridentatus Manfio, Jorge & Ribeiro-Costa sp. nov. is described from the Amazon basin in Brazil (Acre) and Ecuador (Napo), and is included in an updated key to the species of Gibbobruchus Pic. This new species and the recently described G. bergamini Manfio & Ribeiro-Costa are incorporated into a phylogenetic reanalysis of the genus and into a comparative analysis of host plant use and biogeography. Species groups previously proposed were supported and the evolutionary history in host plant-use shows Gibbobruchus conserved at tribe level, Cercideae (Caesalpinioideae), with coordination between biogeographic expansion and host genus shifts. Both species, Gibbobruchus tridentatus Manfio, Jorge & Ribeiro-Costa sp. nov. and G. bergamini, were placed within the group scurra (G. tridentatus (G. scurra (G. cavillator+G. bolivianus+G. bergamini))) and supported by one synapomorphy. Additionally, we update geographic distributions and host plant records. Two hosts, Bauhinia argentinensis Burkart and B. tarapotensis Benth. are recorded for the first time as hosts for the genus and for the subfamily. PMID- 27394755 TI - First records of the genus Cambalida Simon, 1909 (Araneae: Corinnidae, Castianeirinae) from Asia, with the description of two new species from India and one new combination. AB - The hitherto Afrotropical corinnid spider genus Cambalida Simon, 1909 is recorded from Asia for the first time. Detailed morphological descriptions and genitalic illustrations of two new species, C. deorsa sp. n. and C. tuma sp. n. from India, are provided. One new combination is proposed: Cambalida flavipes (Gravely, 1931) comb. nov. The occurrence of distal femoral constrictions of III and IV legs of both male and female are recognised as additional somatic features for the genus Cambalida. The current distribution of all the three Indian Cambalida spp. is mapped. PMID- 27394756 TI - First Record of Anisoptera (Insecta: Odonata) from mid-Cretaceous Burmese Amber. AB - The fossil dragonfly Burmalindenia imperfecta gen. et sp. nov. is described from mid-Cretaceous Burmese amber as the first record of the odonate suborder Anisoptera for this locality and one of the few records from amber in general. The inclusion comprises two fragments of the two hind wings of a dragonfly. The fossil can be attributed to a new genus and species of the family Gomphidae, presumably in the subfamily Lindeniinae, and features a strange teratological phenomenon in its wing venation. PMID- 27394757 TI - Two new species of the genus Aporcelinus Andrassy, 2009 (Nematoda, Dorylaimida, Aporcelaimidae) from Vietnam. AB - Two new species of Aporcelinus from Vietnamese natural habitats are studied, described and illustrated, including line drawings and light microscope (LM) pictures. Aporcelinus paramamillatus sp. n. is characterized by its 1.71-2.14 mm long body, lip region 21-22 MUm broad, odontostyle 22-24 MUm long at its ventral side, neck 451-503 MUm long, uterus tripartite and 71-94 um long, V = 53-54, tail conical with finely rounded tip, ending in a short peg-like terminus, occasionally slightly re-curved dorsad (24-34 MUm, c = 50-77, c' = 0.6-0.9) and unknown male. Aporcelinus paraseychellensis sp. n. is distinguished by its 1.20 1.46 mm long body, lip region 16-18 MUm broad, odontostyle 20 MUm long at its ventral side, neck 354-368 MUm long, uterus tripartite and 176-241 um long, V = 52-54, tail conical with acute tip and hardly re-curved dorsad, spicules 62 MUm long, and 12 regularly spaced ventromedian supplements lacking hiatus. PMID- 27394758 TI - Rediscovery and redescription of Coenagrion persicum (Lohmann 1993) with description of the female, and some notes on habitat selection (Odonata: Coenagrionidae). AB - Coenagrion persicum was described by Heinrich Lohmann in 1993 on the basis of a single male and two larvae captured in 1937 by E.W. Kaiser in Lorestan Province (W-Iran). In June 2015 two of the authors (TS and DI) rediscovered individual rich populations of this species in two Iranian provinces (Lorestan and Esfahan). We could confirm the structural differences of the male appendages between C. persicum and C. pulchellum based on a larger number of specimens than in the original description. The structural differences from C. pulchellum in females and their phenotypic variation pattern is described. Coenagrion persicum and C. pulchellum are also genetically distinct regarding two nDNA gene fragments: arginine methyltransferase (PRMT) and phosphoglucose isomerase (PGI). In contrast with C. pulchellum, C. persicum prefers small springs and running waters with rich herbal vegetation. Our faunistic data indicate that the species is present in the mountains between 1800 m and 2300 m a.s.l.. The species seems to be restricted to W-Iran, where it co-occurs with other rheophilic species. PMID- 27394759 TI - The cane or marine toad, Rhinella marina (Anura, Bufonidae): two genetically and morphologically distinct species. AB - Rhinella marina is a Neotropical toad that has been introduced widely worldwide. Its toxic effects to frog-eating predators threaten the native and domestic fauna of some regions where it has been introduced. Despite previous studies suggesting two genetically distinct cryptic species within R. marina, one east and one west of the Andes, its taxonomic status remained unresolved due to the absence of morphological complementary evidence. For the first time, data from two mitochondrial genes (ND3 and CR) and 23 morphometric landmarks are combined to evaluate the taxonomic status of this species. Our results support the hypothesis of two separate evolutionary lineages within R. marina and demonstrate that these lineages have significantly diverged in skull shape. We identified two distinct morphotypes, one eastern and one Andean western, with no overlapping morphospaces. The geographic pattern of genetic variation was consistent with a stable structured population with no evidence of recent demographic or geographic expansions. The concordance between the observed geographic patterns in morphometric and genic traits calls for the recognition of two species under R. marina name. PMID- 27394760 TI - New and little known species of ptyctimous mites (Acari, Oribatida) from Madagascar. AB - In six sifting litter samples from Madagascar, altogether 26 species of ptyctimous mites, belonging to four families and 11 genera, were found. Three new species, Arphthicarus phoxos sp. nov., Notophthiracarus parapaulianus sp. nov. and Atropacarus (Hoplophorella) paralemurius sp. nov. are described and figured. Keys for species of genera and subgenera Arphthicarus, Notophthiracarus and Atropacarus (Hoplophorella) from Madagascar are presented. PMID- 27394761 TI - CARLOS PRIETO & MARIA A. VARGAS (2016) Elfin butterflies of the genus Rhamma Johnson (Lepidoptera: Lycaenidae: Theclinae): A review of the Colombian species. Zootaxa, 4093(3): 323-342. PMID- 27394762 TI - Phylogenetics, classification, and biogeography of the treefrogs (Amphibia: Anura: Arboranae). AB - A phylogenetic analysis of sequences from 503 species of hylid frogs and four outgroup taxa resulted in 16,128 aligned sites of 19 genes. The molecular data were subjected to a maximum likelihood analysis that resulted in a new phylogenetic tree of treefrogs. A conservative new classification based on the tree has (1) three families composing an unranked taxon, Arboranae, (2) nine subfamilies (five resurrected, one new), and (3) six resurrected generic names and five new generic names. Using the results of a maximum likelihood timetree, times of divergence were determined. For the most part these times of divergence correlated well with historical geologic events. The arboranan frogs originated in South America in the Late Mesozoic or Early Cenozoic. The family Pelodryadidae diverged from its South American relative, Phyllomedusidae, in the Eocene and invaded Australia via Antarctica. There were two dispersals from South America to North America in the Paleogene. One lineage was the ancestral stock of Acris and its relatives, whereas the other lineage, subfamily Hylinae, differentiated into a myriad of genera in Middle America. PMID- 27394763 TI - A revision of Trimuricea Gordon, 1926 (Cnidaria: Octocorallia: Plexauridae) with the description of six new species. AB - The genus Trimuricea Gordon, 1926 is revised. An overview and identification key of all presently known Trimuricea species is given. The type material of Trimuricea africana Gordon, 1926, T. reticulata (Thomson & Simpson, 1909), T. merguiensis Gordon, 1926, T. inermis (Nutting, 1910), T. magna (Nutting, 1910) and T. caledonica Grasshoff, 1999, is re-examined. Trimuricea andamanensis (Thomson & Simpson, 1909) is assigned to Echinogorgia Kolliker, 1865, Trimuricea aff. reticulata (Samimi-Namin & van Ofwegen 2009a) is synonymised with T. persica n. sp.; and T. magna (Nutting, 1910) with T. inermis (Nutting, 1910). Furthermore, six new species are described and depicted, T. bicolor, T. flava, T. omanensis, T. persica, T. tuberculosa, and T. spinosa, increasing the number of known Trimuricea species to eleven. PMID- 27394765 TI - A new mealybug in the genus Pseudococcus Westwood (Hemiptera: Coccomorpha: Pseudococcidae) from North America, with a key to species of Pseudococcus from the New World. AB - A mealybug species that feeds on Agave spp., Pseudococcus variabilis sp. n. (Hemiptera: Coccomorpha: Pseudococcidae), is described from North America. Its entry into the United States was likely via the horticultural trade on its host plants in the genus Agave (Liliales: Agavaceae). Descriptions and illustrations of the adult female and male, diagnosis from congeners in the New World, and a molecular characterization based on COI are provided, as well as a key to adult females of all Pseudococcus species recorded from the New World. PMID- 27394764 TI - Morphological variation in the Brazilian Radiated Swamp Turtle Acanthochelys radiolata (Mikan, 1820) (Testudines: Chelidae). AB - The freshwater turtle Acanthochelys radiolata (Mikan, 1820) is endemic to the Atlantic Forest domain in Brazil and few studies have been done on the morphology, geographic variation and taxonomy of this species. In this paper we record the morphological variation, as well as sexual dimorphism and ontogenetic changes in A. radiolata throughout its distribution range. We analyzed 118 morphological characters from 41 specimens, both quantitative and qualitative, and performed statistical analyses to evaluate size and shape variation within our sample. Morphological analysis revealed that A. radiolata is a polymorphic species, especially regarding color and shape. Two color patterns were recognized for the carapace and three for the plastron. Diagnostic characteristics of the species, such as the rounded tubercles on the neck and the shallow dorsal sulcus between the 2nd and 4th vertebral scutes, varied considerably. Acanthochelys radiolata also showed a high level of ontogenetic variation characterized by a change on the color pattern of plastron and limbs starting from the 4th month of life. Sexual size dimorphism was observed for the first time on nine morphometric variables and females showed larger sizes than males. Based on these results we conclude that A. radiolata represents one single polymorphic species distributed in the lowlands of the Brazilian Atlantic Forest from the state of Alagoas to the state of Rio de Janeiro and the south of Minas Gerais state. PMID- 27394766 TI - A revision of the Australian genus Trachylestes with the description of two new species (Hemiptera: Heteroptera: Reduviidae: Harpactorinae). AB - Two new species, Trachylestes barrowensis sp. nov. from Barrow Island, Western Australia and T. queenslandensis sp. nov. from southeastern Queensland are described, and a key for their separation from other known species of the Australian endemic genus Trachylestes Stal, 1868 (Hemiptera: Heteroptera: Reduviidae: Harpactorinae) is given. PMID- 27394767 TI - Cladistic analysis and description of three new species of the Chilean genus Nanophareus (Opiliones: Gonyleptidae: Pachylinae). AB - Three new species of the Chilean Pachylinae genus, Nanophareus Roewer, 1929 are described: N. bicornutus sp. nov. (Valle de Aconcagua, Zapallar, V Region de Valparaiso), N. maipu sp. nov. (La Rinconada, Quebrada de la Plata, Maipu, Region Metropolitana-Santiago), and N. polyhastatus sp. nov. (El Abanico, VIII Region de Bio-Bio). These three new species were included in a cladistic analysis that resulted in two equally most parsimonious trees (238 steps, C.I. = 0.38; R.I. = 0.51), corroborating the monophyly of Nanophareus. The proposed synapomorphies for Nanophareus remain largely unchanged: an external row of enlarged tubercles inserted amongst small ones on the lateral margin of dorsal scutum; the ventro basal margin of the pedipalpal tibia curved at 90 degrees in lateral view; and retrolateral seta on pedipalpal tibia with an apically bifid socket (socket and seta longer than pedipalpal tibia length), with additional small setae distally. The sister group of Nanophareus, as well as its subfamilial placement, are still unsettled issues that are here further discussed. PMID- 27394768 TI - A review of the pleasing lacewing genus Dilar Rambur (Neuroptera, Dilaridae) from Southeast Asia. AB - The lacewing family Dilaridae (pleasing lacewings) is poorly known in Southeast Asia, currently with only five described species. In this paper, we provide a revision of the species of the genus Dilar Rambur, 1838 from Southeast Asia. Eleven species of Dilar are recorded in this region, with seven species herein described as new to science, i.e. Dilar abnormis Zhang, Liu & Winterton, sp. nov., Dilar lineatus Zhang, Liu & Winterton, sp. nov., Dilar loeinensis Zhang, Liu, Winterton, sp. nov., Dilar ohli Zhang, Liu, Aspock & Aspock, sp. nov., Dilar rotundatus Zhang, Liu & Winterton, sp. nov., Dilar sumatranus Zhang, Liu, Aspock & Aspock, sp. nov., and Dilar zimmermannae Zhang, Liu, Aspock & Aspock, sp. nov. Re-descriptions of Dilar grandis (Banks, 1931), and Dilar marmoratus (Banks, 1931) are also provided. Dilaridae are recorded in Indonesia (Sumatra), Myanmar, and northern Thailand for the first time. A key to the Dilar species from Southeast Asia is given. PMID- 27394769 TI - Orbinia (Polychaeta: Orbiniidae) from the Brazilian coast: two new species and two new records. AB - Representatives of the Family Orbiniidae are very common in marine sediments and are found in both shallow and deep waters. Currently, 26 species and 10 genera have been recorded along the Brazilian coast. The specimens examined in this study were collected at depths ranging from 25 to 400 m in the Campos Basin (20 24oS; 39-42oW), Rio de Janeiro, in the summer and winter of 2008 and 2009. We describe two new species, Orbinia sagitta n. sp. and Orbinia camposiensis n. sp., and record the occurrences of Orbinia johnsoni (Moore, 1909), which was originally described in California, and Orbinia oligopapillata (Lopez, Cladera & San Martin, 2006), which was previously described from the Pacific coasts of Panama. We provide a key for all the species of Orbinia recorded in the Campos Basin. PMID- 27394770 TI - Moenkhausia venerei (Characiformes: Characidae), a new species from the rio Araguaia, Central Brazil. AB - Moenkhausia venerei is described from the rio Araguaia, Mato Grosso, Central Brazil. The new species differs from its congeners, except M. collettii and M. copei, by the combination of the following characters: a longitudinal dark band extending from the tip of the snout to the base of caudal fin; a dark line along the base of the anal fin; and a conspicuous humeral spot. Moenkhausia venerei is distinguished from M. collettii by having a wider and more conspicuous longitudinal dark band and from M. copei by the higher number of anal-fin rays. A discussion about the overall similarity and putative relationship with M. collettii, M. copei, Hemigrammus ulreyi, H. ataktos, and H. barrigonae is provided. PMID- 27394771 TI - Notes on holotypes of hermit crabs (Decapoda: Anomura: Paguroidea) deposited in the collection of Zoological Museum of RAS (Saint-Petersburg, Russia) with remarks on hermit crab diversity along the Russian coast of the Sea of Japan. AB - The holotype of Clibanarius sachalinicus Kobjakova, 1955 and Clibanarius hirsutimanus Kobjakova, 1971 in the collection of Zoological Institute of Russian Academy of Sciences (Saint-Petersburg, Russia) are examined. As a result, Clibanarius hirsutimanus Kobjakova, 1971 is found to be a species of Areopaguristes nigroapiculus (Komai, 2009) while Clibanarius sachalinicus Kobjakova, 1955 is a species of Clibanarius virescens (Krauss, 1843). Remarks on a single record of Diogenes penicillatus Stimpson, 1858 from Shamora Bay (Usury Bay) of the Sea of Japan as well as current faunal list of hermit crabs from the Russian coasts of the Sea of Japan are also presented in the paper. PMID- 27394772 TI - Description of a new species of the genus Chaetostoma from the Orinoco River drainage with comments on Chaetostoma milesi Fowler, 1941 (Siluriformes: Loricariidae). AB - Chaetostoma joropo n. sp. is described from the piedmont of the Orinoco River drainage in Colombia. The new species has been long confused with Chaetostoma milesi, a species with similar overall morphology and color pattern that is restricted to the Magdalena-Cauca River Basin. We diagnose the new species on the basis of morphology as well as a precise description of the color pattern. Chaetostoma joropo n. sp. is also easily distinguished from C. formosae the most similar species and other species inhabiting the Orinoco River drainage in Colombia. Data on ontogenetic variation and sexual dimorphism are provided, as well as natural history notes and remarks on the usage of the name Chaetostoma milesi for specimens from both the Orinoco and Magdalena-Cauca drainages. A discussion on the usage of the name Chaetostoma platyrhynchus is also provided given its current instability in the literature. PMID- 27394774 TI - New species and records of Ischnosoma Stephens (Coleoptera, Staphylinidae, Tachyporinae) from China. AB - More than 1100 specimens of the genus Ischnosoma Stephens, 1829, from China and Taiwan are revised. In all, 29 species and one subspecies are recognized. Seven new species are described and illustrated: Ischnosoma zipapertum sp. n., I. vicinum sp. n., I. foedum sp. n., I. involutum sp. n., I. yunnanum sp. n., I. abstrusum sp. n., and I. gemellum sp. n. Additional records of previously described species are reported. The distributions of all the species are mapped. Four species, Ischnosoma dicoidale discoidale (Sharp, 1888), I. faciatocolle (Champion, 1922), I. hieroboam Kocian, 2003, and I. rosti (Bernhauer, 1923), are recorded from China for the first time. A revised key to the Ischnosoma species of China and Taiwan is presented. PMID- 27394773 TI - Chirality of male genitalia in Otomantis casaica Giglio-Tos, 1915 (Mantodea: Hymenopodidae, Acromantinae). AB - Reversal of male genitalia are known in various insect orders, such as in Odonata, Orthoptera, Dermaptera, Hemiptera and Trichoptera (Schilthuizen 2007) and, within the Dictyoptera, in several species of Ectobiinae (Blattodea) (Bohn 1987), and Mantodea. Balderson (1978) first described reversal of the phallic complex in Stenomantis Saussure and Ciulfina Giglio-Tos, reporting this condition in eleven of 17 specimens representing two species of the latter-informally named as "Ciulfina sp.2" and "Ciulfina sp.7" (see Balderson 1978: 238). Subsequently, Anisyutkin & Gorochov (2004) reported the same condition at the time of describing Haania doroshenkoi from Cambodia. The male external genitalia within the Mantodea ("praying mantises") are markedly asymmetrical and generally develop in a single orientation (Klass 1997; Huber et al. 2007). Typically, the phallic complex consists of three phallic lobes surrounding the gonopore, all contained in a genital chamber between the ninth sternite and the paraprocts. Two of the three phallic lobes (phallomeres of La Greca 1955) are situated above the gonopore-one to the left and one to the right-while the third lies ventral to the genital opening. The right phallomere (RP) (Fig.1) ("right epiphallus" of Beier 1964) is usually dorsally positioned and its base extends almost completely across the wall of the genital chamber. The left phallomere (LP) (Fig.1) ("left epiphallus" of Beier 1964) is the most complex of the three lobes and it lies above the ventral phallomere (VP) (Fig.1) (hypophallus of Beier 1964). PMID- 27394775 TI - Tardigrades from Nahuel Huapi National Park (Argentina, South America) with descriptions of two new Macrobiotidae species. AB - In 31 samples of mosses and lichens collected in the Argentinean province of Rio Negro, 657 tardigrades, 53 exuviae and 219 free-laid eggs were found. In total, 20 species were identified: Diphascon chilenense, Dip. mitrense, Echiniscus bigranulatus, Ech. corrugicaudatus, Ech. merokensis merokensis, Ech. testudo, Hebesuncus mollispinus, Hypsibius convergens, Macrobiotus cf. anderssoni, Mac. andinus, Mac. kazmierskii, Mac. patagonicus, Mesobiotus szeptyckii, Mes. pseudoblocki sp. nov., Milnesium argentinum, Mil. beatae, Mil. brachyungue, Mil. granulatum, Mopsechiniscus granulosus, Minibiotus pseudostellarus sp. nov. Of the two new species, Mesobiotus pseudoblocki sp. nov. is most similar to Mes. blocki, but it differs mainly by the lack of dentate lunules, smaller eggs and presence of reticular design on egg processes. Minibiotus pseudostellarus sp. nov. is most similar to Min. constellatus, Min. eichhorni, Min. sidereus or Min. vinciguerrae, but it differs from them by the presence of 'pseudo-star'-shaped pores in the dorsal cuticle instead of fully developed 'stars' and by other morphometric characters. PMID- 27394776 TI - A new genus of Entomobryinae (Collembola, Entomobryidae) from Brazilian Amazon with body scales and dental spines. AB - A new monotypic genus of Entomobryinae from Brazilian Amazon is described and illustrated. Amazhomidia gen. nov. is similar to other genera of the subfamily, especially to Sinhomidia Zhang, in presence of apically pointed scales on body dorsally and spines on dens. It differs from all other genera of Entomobryinae by the combination of: bifurcate prelabral chaetae, cephalic groove with scale-like chaetae and two transverse rows macrochaetae present on anterior central region of the abdominal IV segment. Amazhomidia ducke sp. nov., the type species of the new genus is described. An identification key to the genera of Entomobryidae with scales and dental spines is also provided. PMID- 27394777 TI - The Pselaphinae (Coleoptera: Staphylinidae) of Madagascar. IV. Contribution to the knowledge of subtribes Hoplitoxenina and Dimerometopina with description of a new species of Hadrophorus Fairmaire, 1898. AB - The subtribe Dimerometopina Celis, 1970 is reestablished. A key and catalogue of the species of subtribes Hoplitoxenina and Dimerometopina is provided; a key to species of the genus Hadrophorus Fairmaire, 1898 is also given. Hadrophorus martinkae sp. n. from Madagascar, Montagne d'Ambre is described. New records for Hadrophorus spinipennis Celis, 1969 (Madagascar, Zombitse N.P.) and Hoplitoxenus joannae Jeannel, 1960 (Cameroon and Gabon, first record) are provided. PMID- 27394778 TI - Review of the genus Anthonympha Moriuti, 1971 (Lepidoptera: Plutellidae) from China, with descriptions of four new species. AB - Chinese species of Anthonmypha Moriuti are reviewd. Five species are recognized, four of which are described as new: Anthonympha truncata sp. nov., A. trapezia sp. nov., A. ligulacea sp. nov. and A. reniforma sp. nov. Images of adults and genitalia are provided, along with a key to distinguishing all the Chinese species. PMID- 27394779 TI - Grass-thrips of the genus Oelschlaegera (Thysanoptera: Thripidae), with the first description of a male. AB - The Chirothrips-like species are grass-living members of the Thysanoptera family Thripidae. All of these species were assigned to the genus Chirothrips Haliday (1836) until Hood (1954) erected Agrostothrips for a single species from South Africa, and Knechtel (1960) described a new monotypic genus Ereikethrips from Romania. An extensive identification key to the 52 species of Chirothrips then known was published by zur Strassen (1960), and the generic classification remained stable for the next 30 years. However, Bhatti (1990) erected five new genera for several species of this genus (Afrothripella, Arorathrips, Konothrips, Longothrips and Oelschlaegera). Bhatti also included three further species in Agrostothrips, but Minaei & Mound (2010) regarded Agrostothrips as a synonym, and returned all four species to Chirothrips. In the most recent study of the group, Nakahara & Foottit (2012) added one monobasic genus, Unilobothrips, and provided an identification system to the 36 Chirothrips-group species known from the Americas. Thus, eight genera are currently included in this genus group (Table 1). PMID- 27394780 TI - TATSUYA KAGA (2016) A new jellynose, Ateleopus edentatus, from the western Pacific Ocean (Teleostei: Ateleopodiformes: Ateleopodidae). Zootaxa, 4083 (4): 562-568.
. PMID- 27394781 TI - Additional records of the genus Hylaeus Fabricius, 1793 (Hymenoptera: Apoidea: Colletidae) from Siberia, with description of a new species. AB - As a supplement to a previously published study on Siberian Hylaeus species, we here report further records of twenty six rarely collected and little known species. Thirty two species are currently known from Siberia, including Hylaeus dorni Dathe, 1986, H. gredleri Forster, 1871, H. hungaricus (Alfken, 1905), H. moricei (Friese, 1898), H. nimbatus Dathe, 1986, H. oehlkei Dathe, 2010 and H. stubbei Dathe, 1986, which are reported from Russia for the first time, and H. brevicornis Nylander, 1852, H. communis Nylander, 1852, H. pfankuchi (Alfken, 1919) and H. styriacus Forster, 1871, which are newly recorded from Siberia. Hylaeus (Hylaeus) pesenkoi Proshchalykin & Dathe, sp. nov. is described as new from Siberia (Altai Republic and Tyva Republic) and neighbouring Mongolia (Khovd and Govi-Altai Aimags). The females of H. dorni Dathe, 1986 and H. oehlkei Dathe, 2010 are described for the first time; H. peregrinus Dathe, 1986 was recognised as the female of H. stubbei Dathe, 1986 and is treated as a new synonym. PMID- 27394782 TI - A revision of the genus Macrolygistopterus Pic, 1929 (Coleoptera, Lycidae, Calochromini). AB - A taxonomic review of the Lycid genus Macrolygistopterus Pic, 1929 with illustrations of diagnostic characters, geographic distribution maps and an identification key to the species is presented. Also, a key to the world Calochromini is given. Of the 12 species of the genus, 9 were studied: M. succinctus (Latreille, 1811), M. quadricostatus (Buquet, 1842), M. caeruleus (Gorham, 1884), M. germaini Pic, 1930, M. grandjeani Pic, 1930, M. subparallelus Pic, 1930, M. testaceirostris Pic, 1930, M. simoni Pic, 1930 and M. kirschi Pic, 1931 were redescribed and their status as valid species is confirmed. The lectotypes and paralectotypes were designated for all those examined species. M. bilineatus (Pic, 1923), M. diversicornis Pic, 1930 and M. bipartitus Pic, 1933 remain as valid species since these specimens were not available for this study. M. succinctus var. scutelaris Pic, 1930 is proposed here as new junior synonym of M. succinctus (Latreille, 1811). PMID- 27394783 TI - Phylogenetic evaluation of taxonomic definition of didelphid mouse opossum of the genus Thylamys from valleys of Coquimbo region, Chile. AB - Only two species of Didelphidae are currently recognized in Chile, the sister species Thylamys elegans, endemic of Mediterranean ecorregion and Thylamys pallidior, the inhabitant of the Puna and desert canyons. Three subspecies have been described for T. elegans: T. e. elegans, T. e. coquimbensis and T. e. soricinus. However, a recent study based on morphological analyses, synonymized T. elegans coquimbensis from the Coquimbo valleys (30-31 degrees S) with T. pallidior and proposed that T. elegans and T. pallidior could be in sympatry at Coquimbo valleys between Fray Jorge (30 degrees 40'S) and Paiguano (30 degrees 02' S). We assess the current definition of T. e. coquimbensis and T. e. elegans, as well as this taxonomical conflict among the mouse opossums from the Coquimbo valleys through phylogenetic analyses of cytochrome b mitochondrial gene sequences. In this study, for the first time, we used specimens from the type localities of T. e. coquimbensis and T. e. elegans. In addition, we analyzed diagnostic cranial structures for this taxonomic revision. The results supported two allopatric clades, allowing us to keep the taxonomic definition of T. e. elegans and T. e. coquimbensis as phylogenetic reciprocal monophyletic clades and polyphyletic with T. pallidior. This result corroborates previous morphological analyses, which support that mouse opossums from the Coquimbo valleys are T. e. coquimbensis, thus extending its geographic distribution to the coast of Coquimbo and Atacama regions. We don't have evidence for sympatric distribution between T. elegans and T. pallidior in the Coquimbo region. PMID- 27394784 TI - Comments on the status of Xiphidiopsis quadrinotata Bey-Bienko, 1971 and related species with one new genus and species (Orthoptera: Tettigoniidae: Meconematinae). AB - Based on the collections of the Museum of Hebei University, the paper comments Xiphidiopsis quadrinotata Bey-Bienko, 1971 status and reinstates Xizicus (Axizicus) xizangensis Jiao & Shi, 2013 as a valid species. Meanwhile, Alloteratura (Meconemopsis) Karny, 1924 is redefined and one new genus of Meconematinae, Nigrimacula Shi, Bian & Zhou gen. nov., mainly distributed in South China, is erected. The new genus includes three previously known species: Xiphidiopsis quadrinotata Bey-Bienko, 1971, Xizicus (Axizicus) xizangensis Jiao & Shi, 2013 and Meconemopsis paraquadrinotata Wang, Liu & Li, 2015 and one new species, Nigrimacula binotata Shi, Bian & Zhou sp. nov. The male of Xiphidiopsis quadrinotata Bey-Bienko, 1971 and female of Xizicus (Axizicus) xizangensis Jiao & Shi, 2013 are described for the first time. A key to the species based on the morphology and a distribution map are included. PMID- 27394785 TI - Five new species and key for Australian Epyris Westwood (Hymenoptera, Bethylidae). AB - Epyris Westwood, 1832 is the largest genus within Bethylidae, but few species are known from Australia, with only two species described. Following trips undertaken by the author to sort material from the Canadian National Collections, Queensland Museum, and Australian National Insect Collection, the number of described species is expanded to seven with the addition of E. loisae Tribull, sp. nov., E. herschae Tribull, sp. nov., E. carpenteri Tribull, sp. nov., E. azevedoi Tribull, sp. nov., and E. fulgeocauda Tribull, sp. nov. Descriptions and illustrations of each new species are provided, as well as a key to the known Australian Epyris species. PMID- 27394786 TI - A new species of Metacoelura (Collembola: Paronellidae) from Australia, and redescription of Metacoelura articulata. AB - The genus Metacoelura Salmon, 1951 is unusual as it possesses some characters typical of the family Entomobryidae and others of the Paronellidae. Three species and subspecies have been described, all from Australasian tropical regions. Metacoelura articulata is redescribed and a new species, Metacoelura majeri sp. nov., is described based on material collected in Australia. A key to species of the genus is provided. PMID- 27394787 TI - A new species of Catocala Schrank, 1802 (Lepidoptera: Noctuidae) from Primorsky Krai, Russia. AB - Here we describe Catocala didenko sp. n. as new for the noctuid genus Catocala Shrank, differing from Catocala duplicata Butler, 1885 and Catocala gansan Ishizuka & Wang, 2013 on wing pattern, male genitalia, and COI 5' mitochondrial DNA. These three species, along with Catocala dissimilis Bremer, 1861, comprise a small and distinctive species group within the genus. Exemplary uncommon morphological characters for this group include: extensive area of ventral side of claspers unsclerotized (Fig. 17); claspers with a subapical ventral bulging projection (Fig. 17); sclerotized apex of claspers greatly expanded laterally (Fig. 17); diaphragma posterior to anellus lightly pigmented (Fig. 22); distinctive anellus shape (Fig. 22); uncus setae longest and densest at base (Fig. 21); and approximately 17-20 coils on the receptacle duct (Fig. 56). PMID- 27394788 TI - JODI J. L. ROWLEY, DAO T. A. TRAN, DUONG T. T. LE, VINH Q. DAU, PEDRO L. V. PELOSO, TRUONG Q. NGUYEN, HUY D. HOANG, TAO T. NGUYEN & THOMAS ZIEGLER (2016) Five new, microendemic Asian Leaf-litter Frogs (Leptolalax) from the southern Annamite mountains, Vietnam. Zootaxa, 4085(1): 063-102. PMID- 27394789 TI - Two new Bent-toed Geckos of the Cyrtodactylus pulchellus complex from Peninsular Malaysia and multiple instances of convergent adaptation to limestone forest ecosystems. AB - A new species of limestone cave-adapted gecko of the Cyrtodactylus pulchellus complex, C. hidupselamanya sp. nov., is described from an isolated karst formation at Felda Chiku 7, Kelantan, Peninsular Malaysia. This formation is scheduled to be completely quarried for its mineral content. From what we know about the life history of C. hidupselamanya sp. nov., this will result in its extinction. A new limestone forest-adapted species, C. lenggongensis sp. nov., from the Lenggong Valley, Perak was previously considered to be conspecific with C. bintangrendah but a re-evaluation of morphological, color pattern, molecular, and habitat preference indicates that it too is a unique lineage worthy of specific recognition. Fortunately C. lenggongensis sp. nov. is not facing extinction because its habitat is protected by the UNESCO Archaeological Heritage of the Lenggong Valley due to the archaeological significance of that region. Both new species can be distinguished from all other species of Cyrtodactylus based on molecular evidence from the mitochondrial gene ND2 and its flanking tRNAs as well as having unique combinations of morphological and color pattern characteristics. Using a time-calibrated BEAST analysis we inferred that the evolution of a limestone habitat preference and its apparently attendant morphological and color pattern adaptations evolved independently at least four times in the C. pulchellus complex between 26.1 and 0.78 mya. PMID- 27394790 TI - The cicada genus Guyalna Boulard & Martinelli, 1996 (Hemiptera: Cicadidae: Cicadinae: Fidicinini): generic description, twelve new combinations, and a key to species. AB - The cicada genus Guyalna Boulard and Martinelli, 1996 is described fully for the first time. Dorisiana bogotana (Distant, 1892), Dorisiana brisa (Walker, 1850), Fidicinoides coffea Sanborn, Moore & Young, 2008, Fidicinoides distanti (Goding, 1925), Fidicinoides flavipronotum Sanborn, 2007, Dorisiana glauca (Goding, 1925), Dorisiana panamensis (Davis, 1939), Fidicinoides variegata (Sanborn, 2005), and Dorisiana viridifemur (Walker, 1850) are transferred to the genus Guyalna to become Guyalna bogotana (Distant, 1892) n. comb., Guyalna brisa (Walker, 1850) n. comb., Guyalna coffea (Sanborn, Moore & Young, 2008) n. comb., Guyalna distanti (Goding, 1925) n. comb., Guyalna flavipronotum (Sanborn, 2007) n. comb., Guyalna glauca (Goding, 1925) n. comb., Guyalna panamensis (Davis, 1939) n. comb., Guyalna variegata (Sanborn, 2005) n. comb., and Guyalna viridifemur (Walker, 1850) n. comb., respectively. Fidicinoides cachla (Distant, 1899), Fidicinoides compostela (Davis, 1934), Fidicinoides guayabana Sanborn, Moore & Young, 2008, are transferred to Dorisiana Metcalf, 1952 to become Dorisiana cachla (Distant, 1899) n. comb., Dorisiana compostela (Davis, 1934) n. comb., and Dorisiana guayabana (Sanborn, Moore & Young, 2008) n. comb., respectively. The current 25 species of the genus are listed along with their synonymies and known distribution of each species. Finally, a key to the species of Guyalna is provided. PMID- 27394791 TI - The immature stages of Micropygomyia (Coquillettimyia) chiapanensis (Dampf) (Diptera: Psychodidae, Phlebotominae). AB - The egg exochorion, larval instars and pupa of the phlebotomine sand fly Micropygomyia (Coquillettimyia) chiapanensis (Dampf) are described and illustrated based on specimens collected in the locality of Farallon, municipality of Actopan, Veracruz, Mexico. Morphology of fourth instar larval mouthparts, particularly the incisor lobe and molar lobe shape of mandible, could be important for species identification of immature Phlebotominae. In this work is compared the pupal chaetotaxy of Mi. chiapanensis with other species previously described. The fourth instar larva of Mi. chiapanensis is compared with other species of this genus, the most important differentiating characters being the size, shape and position of the abdominal dorsal internal seta. PMID- 27394792 TI - A new genus and species of the paraneopteran family Archipsyllidae in mid Cretaceous amber of Myanmar. AB - Paraneoptera is a group of orders, representing one of the highly diverse clades of winged insects. Paleozoic and Mesozoic fossil paraneopterans include a few primitive species, which are significant for understanding the early evolution of Paraneoptera. Here we report a new genus and species, namely Burmopsylla maculata gen. et sp. nov. from the mid-Cretaceous (ca. 99 Myr) amber of Myanmar. The new genus belongs to the family Archipsyllidae by having hindwing similar to forewing (shape, size and venation), presence of forewing ra-rp, rp-m and cua-cup crossveins, two-branched R, four-branched M, and four-segmented tarsus. The new species represents the second species of Archipsyllidae in Cretaceous Burmese amber. PMID- 27394793 TI - Review of the genus Hypobarathra Hampson, 1905 (Lepidoptera, Noctuidae, Hadeninae) with description of a new species. AB - The present study was initiated upon finding an unknown Hypobarathra species during a collecting expedition to the higher regions of western Sichuan Province in China in 2015. The genus previously contained only two Palaearctic species with remarkably different external appearance and distribution pattern. Interestingly, all three species of Hypobarathra are adapted to completely different eco zones and habitats, which are discussed under each species. According to Hacker et al. (2002), the closest relatives of the genus are Melanchra Hubner, [1820] 1816 and Odontestra Hampson, 1905. This statement should be corrected, since Hypobarathra is forming a common clade with Melanchra, Ceramica Guenee, 1852 and Ebertidia Boursin, 1968, while Odontestra representing another lineage within the tribus Hadeninae. PMID- 27394794 TI - A new species of Falsocaenia Pic, 1922 from Amazonian Rainforest (Coleoptera: Lycidae) with an updated key to the species. AB - While searching for Calochromini (Coleoptera: Lycidae) specimens in entomological collections and identifying other Lycidae, a new species of Falsocaenia Pic, 1922 was found in the collection of Instituto Nacional de Pesquisas da Amazonia (INPA). This genus is one of the smallest in the tribe Calopterini with 13 known species, two of which were recently described by Bocakova et al. (2012) in their revision of the genus, and can be found in Central and South America. PMID- 27394795 TI - Fausto E. Barbo, Joao Luiz Gasparini, Antonio P. Almeida, Hussam Zaher, Felipe G. Grazziotin,Rodrigo B. Gusmao, Jose Mario G. Ferrarini & Ricardo J. Sawaya (2016)Another new and threatened species of lancehead genus Bothrops (Serpentes, Viperidae) from Ilha dos Franceses, Southeastern Brazil. Zootaxa 4097 (4): 511 529. PMID- 27394796 TI - The myrmicine ant genus Metapone Forel (Hymenoptera: Formicidae): a global taxonomic review with descriptions of twelve new species. AB - The 28 known species of Metapone are monographed and illustrated. Twelve are described as new: M. africana, Gabon; M. balinensis, Bali, Indonesia; M. enigmatica, northeast New Guinea; M. hoelldobleri, northeast Queensland, Australia; M. javana, Java, Indonesia; M. manni, Viti Levu, Fiji; M. mathinnae, Flinders Island, Tasmania, Australia; M. philwardi, northeast New Guinea; M. salomonis, Guadalcanal, Solomon Islands; M. tecklini, northeast Queensland; M. titan, New Ireland, Papua New Guinea; M. wallaceana, Lombok, Indonesia; spp.n. New synonymies include M. greeni Forel = M. johni Karavaiev (Sri Lanka) syn.n, and M. jacobsoni Crawley (Sumatra) = M. nicobarensis Tiwari & Jonathan (Great Nicobar Island) syn.n. PMID- 27394797 TI - A new diminutive sisorid catfish (Actinopterygii: Siluriformes) from northeastern India. AB - This study describes a new diminutive sisorid catfish from the upper reaches of the Karnaphuli River drainage in northeastern India. The new species can be distinguished from congeners in having a combination of: length of dorsal-fin spine 18.0-21.6% SL; 4-10 serrations on the anterior edge of the dorsal spine; length of pectoral-fin spine 20.7-26.1% SL; length of adipose-fin base 21.5-26.3% SL; body depth at anus 12.3-15.9% SL; caudal peduncle depth 7.5-9.8% SL; caudal peduncle length 17.0-20.5% SL; pale, y-shaped marking on dorsal surface of head; sides of body with pale yellowish patches and irregular bands. PMID- 27394798 TI - Flightless Notaris (Coleoptera: Curculionidae: Brachycerinae: Erirhinini) in Southwest China: monophyly, mtDNA phylogeography and evolution of habitat associations. AB - This paper reports the recent discovery of flightless populations of weevils of the genus Notaris in Yunnan and Sichuan provinces of China. Specimens were found in the middle or high altitude mountains (2440-4195 m), by either sifting leaf litter in the deciduous forest and among alpine Rhododendron shrubs, or by turning rocks in the alpine zone. These finds extend southwards the Asian range of this Holarctic genus and report its highest altitudinal records. DNA barcodes of 127 specimens were phylogenetically analysed, of them 42 are those of newly discovered Notaris from Southwest China. The genera Notaris and Tournotaris consistently formed a clade, with Tournotaris nested inside Notaris in Maximum Parsimony (MP) and Maximum Likelihood (ML) analysis. The newly discovered flightless Notaris from Southwest China were either monophyletic (MP) or paraphyletic with respect to volant Holarctic N. aethiops (ML); the latter placement being likely an artefact. A strict linear molecular clock approach suggests a pre-Pliocene separation of Notaris populations in Southwest China. Habitat associations of these high-altitude flightless Notaris contrast sharply with that of the predominantly volant lowland riparian Notaris and other Erirhinini. We hypothesis that evolution of habitat selection in Notaris went from lowland riparian, to high altitude (via uplift of the Tibetan Plateau and adjacent regions of Central Asia), and then to forest leaf litter (via subsequent erosions of isolated mountains such as Emei Shan in Sichuan losing the alpine zone and forcing Notaris into the forest floor). Taxonomic uncertainty of Asian Notaris is addressed and remains unresolved due to uninformative morphology and conflicting DNA signal. Identities of two obscure and likely closely related species, Notaroides brevirostris and Notaris kozlovi from nearby SE Qinghai and NW Sichuan, respectively, are discussed and illustrated. Pending further research, all reported flightless Notaris from Yunnan and Sichuan are hypothesised to form a clade, for which the available name N. kozlovi is used. Habitus and genitalia of Notaris specimens from the newly detected populations are illustrated. PMID- 27394799 TI - Notes on the genus Polycaena Staudinger (Lepidoptera: Riodinidae) with descriptions of two new species from China. AB - Polycaena sejila sp. n. (Riodinidae: Nemeobiinae: Nemeobiini: Nemeobiina) and P. wangjiaqii sp. n. are described from Tibet Autonomous Region and Yunnan province respectively. P. lua minor is raised to full species, namely P. minor stat. n.; P. lama qinghaiensis syn. n. is recognized as a new junior synonym of P. kansuensis; P. lama taibaiensis is transferred as a subspecies of P. lua, namely P. lua taibaiensis stat. n.. The male genitalia of P. sejila, P. wangjiaqii, P. lama, P. kansuensis, P. lua lua, P. lua taibaiensis and P. minor are described and illustrated. A checklist of the genus Polycaena is updated and a key to species of the genus is provided. PMID- 27394800 TI - Description of a new species of Chonala (Lepidoptera, Nymphalidae, Satyrinae) from NW Yunnan, China. AB - A new species, Chonala huertasae Lang & Bozano sp. nov., is described from Dulong jiang valley, West slope of Mts. Gao-li-gong, NW Yunnan Province, SW China. A key to species and subspecies of the genus Chonala is given. PMID- 27394801 TI - A new species of Tamenes Gounelle, 1912 (Coleoptera, Cerambycidae). AB - After the original description of Tamenes sarda Gounelle, 1912, based on a single male from Panama, the species was rarely mentioned in the literature except in catalogues and checklists. An exception appeared in Monne & Martins (1973) who speculated that Palaeotrachyderes Tippmann, 1960 may be equal to Tamenes (translated): "In 1960 Tippmann described Palaeotrachyderes, relating it with Lissonotini. The type species, P. laticornis, is also from Chiriqui [the type locality of T. sarda]. Those facts lead us to assume that the genera may be very close or even synonyms, which must be proven upon examination of material of that area." However, the scutellum of P. laticornis is notably small, while in T. sarda it is distinctly large. This feature makes it unlikely that those genera are synonymous. PMID- 27394802 TI - Revision of the genus Allometopon Kertesz (Diptera: Clusiidae). AB - The genus Allometopon Kertesz is revised, recognizing 68 species, including 5 undescribed species known only from females. The genus is mostly known from the Australian (30 spp.) and Oriental Regions (33 spp.-only one unnamed female is found in both Australian and Oriental Regions), but also the Afrotropical (5 spp.) and Palaearctic Regions (1 sp.). Most Allometopon are new to science, with 40 new species described here: A. acum, A. asylum, A. atribatum, A. bharetum, A. bivittatum, A. cavernosium, A. cheiris, A. conopeum, A. eotoxon, A. fumihalteratum, A. fuscinum, A. gaimarii, A. giallo, A. glochis, A. gracile, A. hauseri, A. hesperotoxon, A. hirsutum, A. horridum, A. infernum, A. juxtum, A. kokodensis, A. lunatum, A. lux, A. macalpinei, A. machaeroges, A. magnum, A. monstrum, A. nyx, A. phenomena, A. philomela, A. platystylum, A. plicatum, A. procne, A. selenis, A. solare, A. suspirium, A. tenebrae, A. tetrathrix, and A. trilobellum. Calometopon Frey syn. nov. (subgenus of Allometopon with type species A. nobile Frey, by original designation) is included as a junior synonym of Allometopon. Sobarocephala geniculata Sasakawa is recombined as Allometopon geniculatum comb. nov. A key, illustrations and photographs are provided for species. PMID- 27394803 TI - Revision of the genus Pselaphomorphus Motschulsky, 1855 (Staphylinidae, Pselaphinae: Jubini). AB - The genus Pselaphomorphus Motschulsky, 1855 is revised to include 33 species. The type species, Pselaphomorphus sculpturatus Motschulsky, 1855, and the previously described species P. longiceps Raffray, 1890 and P. microphthalmus Raffray, 1890 are redescribed, and the original description of P. brevipennis Raffray, 1917 and P. bruchi Raffray, 1918 are translated from Latin and French to English. The following species are described as new: P. acutispinosus n. sp. from Peru, P. agametopus n. sp. from Colombia, P. azuayensis n. sp. from Ecuador, P. bolivarensis n. sp. from Venezuela, P. breviantennae n. sp. from Bolivia, P. carenobothrus n. sp. from Peru, P. carltoni n. sp. from Ecuador, P. cayennensis n. sp. from French Guiana, P. chandleri n. sp. from Panama, P. fluminosus n. sp. from Venezuela, P. iguazuensis n. sp. from Argentina, P. incorum n. sp. from Peru, P. longissimus n. sp. from Panama, P. macrommatus n. sp. from Ecuador, P. maldonadensis n. sp. from Peru, P. mayaorum n. sp. from Honduras, P. melanus n. sp. from Costa Rica, P. montsineryensis n. sp. from French Guiana, P. motschulskyi n. sp. from Costa Rica, P. newtoni n. sp. from Brazil, P. parki n. sp. from Costa Rica, P. raffrayi n. sp. from Peru, P. santaecrucis n. sp. from Bolivia, P. simplicipenis n. sp. from French Guiana, P. thayerae n. sp. from Brazil, P. tucumanensis n. sp. from Argentina, P. veracruzanus n. sp. and P. wagneri n. sp., both from Mexico. A key to the species, color photographs and genitalia illustrations are provided. PMID- 27394804 TI - Systematics of small Gehyra (Squamata: Gekkonidae) of the southern Kimberley, Western Australia: redescription of G. kimberleyi Borner & Schuttler, 1983 and description of a new restricted range species. AB - Ongoing fieldwork and molecular research continues to reveal that the monsoonal tropics of northern Australia contain more vertebrate species than currently recognised. Here we focus on two morphologically distinctive, yet unrecognised forms in the genus Gehyra from the southern Kimberley region and surrounding deserts. We base our descriptions on a combination of unpublished genetic data and a morphological examination of voucher specimens. We recognise and redescribe G. kimberleyi, a species with a broad distribution extending over most of the south-west Kimberley, across the Great Sandy Desert and into the far northern Pilbara. This species has been previously assigned to G. pilbara owing to its frequent occurrence on termite mounds and short snout, but can be distinguished from G. pilbara and other regionally sympatric Gehyra by its moderate body size, moderate number of pre-cloacal pores in males (12-17) and aspects of dorsal colouration. We also describe G. girloorloo sp. nov., a small rock-dwelling species with a short snout, low number of pre-cloacal pores in males (8-11) and pinkish-grey dorsal colouration with alternating series of indistinct pale spots and irregular transversely-aligned dark blotches. The new species appears to be restricted to a relatively small region of exposed limestone karst in the south west Kimberley and is entirely circumscribed by morphologically similar congeners. PMID- 27394805 TI - Sasanidus, a new generic name for Noemacheilus kermanshahensis Banarescu & Nalbant, with discussion of Ilamnemacheilus and Schistura (Teleostei; Nemacheilidae). AB - Sasanidus, new genus, is described for Noemacheilus kermanshahensis Banarescu & Nalbant, endemic to the Karkheh and Karun drainages in Iran. Sasanidus kermanshahensis was initially identified as a species in Oxynoemacheilus, from which it is distinguished by the absence of an external sexual dimorphism (i.e. longer pectoral fin, and nuptial tubercles on fins, head and back in males). Sasanidus is distinguished from all other genera of Nemacheilidae in the Middle East by a combination of the following character states: pelvic-fin origin behind of a vertical of the dorsal-fin origin, anus about one eye diameter in front of the anal-fin origin, dorsal adipose keel absent, a high crest on the bony capsule of the swim bladder present and colour pattern marbled or mottled or with an irregularly shaped midlateral stripe. Ilamnemacheilus longipinnis was examined and no difference could be found between Ilamnemacheilus and Oxynoemacheilus. Therefore, Ilamnemacheilus is treated as a synonym of Oxynoemacheilus. COI barcode sequences from all nemacheilid loach genera occurring in the Middle East and western India are analysed jointly for the first time. The view that Schistura is a paraphyletic assemblage is supported by the clustering of DNA sequences from 45 specimens placed in at least 20 species in the genus Schistura analysed here. PMID- 27394806 TI - First record of the tribe Phlepsiini (Hemiptera: Cicadellidae: Deltocephalinae) from China, with description a new genus and species. AB - The tribe Phlepsiini Zahniser & Dietrich, 2013 is reported from China for the first time based on a new genus and species, Brevivalvala melanosticta gen. et sp. nov., here described and illustrated from Yunnan Province. This new genus can be distinguished from other genera in this tribe by the short valve and subgenital plate without macrosetae. PMID- 27394807 TI - A new species of Dyspessa Hubner, (Lepidoptera, Cossidae) from Western China, with catalogue of Chinese species of the genus. AB - The genus Dyspessa is the largest genus of carpenter moths including 60 valid species, widely distributed in Western Palearctic, especially in Sahara desert, Minor Asia, Iran and Central Asia (Yakovlev 2011; 2015). Most of the species have a small distribution range, limited by mountain ranges or deserts (Yakovlev & Dubatolov 2013). The only known trophic preferences of Dyspessa are their specialization to different species of the plant genus Allium (Alliaceae) (Yakovlev 2015). There are only three species known from China, Xinjiang Uyghur Autonomous Region: Dyspessa saissanica Yakovlev, 2014 (erroneously listed for Hami (Xinjiang) as Dyspessa salicicola (Eversmann, 1848) (Yakovlev 2005), Dyspessa tristis A. Bang-Haas, 1912 (known by a single male from Chinese part of Mongolian Altai mountains collected by Grigory Grumm-Grzhimaylo (probably in June 2003, Kurtu river of Kran river basin) and Dyspessa rueckbeili Yakovlev, 2007, described from Central Asia, Altyn Tagh [Altun Shan] (Altun Shan is a mountain range in northwestern China that separates the eastern Tarim Basin from the Tibetan Plateau (Yakovlev 2007). The western third is in Xinjiang while the eastern part forms the border between Qinghai to the south and Xinjiang and Gansu to the north). During a study of the new Dyspessa specimens from Western China, West South part of Xinjiang the new species, described below, was found. PMID- 27394808 TI - Redescription of Draposa subhadrae (Patel & Reddy, 1993) (Araneae: Lycosidae, Pardosinae). AB - Draposa Kronestedt, 2010 is a small genus of Pardosinae spiders. Currently it encompasses 10 species (World Spider Catalog 2016) distributed from Pakistan to Southeast China. Most species of the genus, except for D. porpaensis (Gajbe, 2004), are known from both sexes and were described or redescribed by Kronestedt (2010). Two other species, D. amkhasensis (Tikader & Malhotra, 1976) and D. burasantiensis (Tikader & Malhotra, 1976), both recently transferred to Draposa (Dhali et al. 2012 ), are doubtful because their copulatory organs are not properly illustrated and differ from the type species and other species of the genus. The male of Draposa subhadrae (Patel & Reddy, 1993) remains known by very poor original drawings because Kronestedt (2010) was not able to study types. While studying material from Sri Lanka collected by us, we found one sample with two females belonging to D. subhadrae and two males of Draposa having the same colour pattern and size. We concluded that these specimens are conspecific. The goal of this paper is to provide an illustrated redescription of this species. PMID- 27394809 TI - A new species of Cangshanaltica Konstantinov et al., a moss-inhabiting flea beetle from Thailand (Coleoptera: Chrysomelidae: Galerucinae: Alticini). AB - Moss cushions represent an interesting, but poorly understood habitat, which hosts many species of flea beetles (Coleoptera: Chrysomelidae: Galerucinae: Alticini). However, the diversity of moss-inhabiting flea beetles is not well studied, and collecting in tropical and subtropical locations that were not sampled in the past led to the discovery of many new species (Konstantinov et al. 2013). Here, a new species of a moss-inhabiting flea beetle from the genus Cangshanaltica Konstantinov et al. 2013 is described and illustrated. This genus is one of the recently described moss-inhabiting flea beetle genera and before this study, only one species was known (Konstantinov et al., 2013). This publication raises the number of flea beetle species that are known to occur in moss cushions around the world to 30, distributed among 15 genera. PMID- 27394810 TI - The identity of Orthaea maculifera, with proposal of a new synonymy (Hemiptera: Heteroptera: Rhyparochromidae). AB - Orthaea maculifera Uhler, 1861 (Hemiptera: Heteroptera: Lygaeoidea: Rhyparochromidae) was described by Uhler (1861) based on an unspecified number of female specimens from Hong Kong. For a long time this species remained of unknown identity and uncertain generic placement (Stal 1874, Lethierry & Severin 1894). As a result of the synonymy of the genus Orthaea Dallas, 1852 with Pachybrachius Hahn, 1826 proposed by Barber (1939) (not accepted by Harrington (1980) and subsequent workers), Slater (1964) listed the species within the genus Pachybrachius. Although the species has still been regarded as of unknown identity (Zheng & Zou 1981), this generic placement has been followed by subsequent authors (Pericart 2001). PMID- 27394811 TI - Evolution in karst massifs: Cryptic diversity among bent-toed geckos along the Truong Son Range with descriptions of three new species and one new country record from Laos. AB - Species designated as 'cryptic' share a similar morphotype, and are often only clearly separable by molecular data. Cyrtodactylus, the most diverse gecko genus of the family Gekkonidae, is a prime example, because many morphologically similar taxa have only recently been identified as new species as a result of available genetic evidence. However, while cryptic diversity of Cyrtodactylus is already well documented on the Vietnamese side of the Truong Son range, only scarce data is available from central Laos. In this study, we address this issue by means of an integrative approach, which employs morphological, molecular, and ecological data to distinguish cryptic species of the Cyrtodacylus phongnhakebangensis species group primarily distributed along the northern Truong Son Range. Our analyses based on 12 selected morphological characters, a partial mitochondrial gene (COI), and five ecological parameters revealed three undescribed cryptic Cyrtodactylus species from Hin Nam No National Protected Area, which are described as Cyrtodactylus calamei sp. nov., Cyrtodactylus hinnamnoensis sp. nov., and Cyrtodactylus sommerladi sp. nov. A fourth discovered Cyrtodactylus population in Hin Nam No proved to be the first country record of C. cryptus for Laos. Our results highlight the importance of applying an integrative approach to resolving the taxonomy of complex and cryptic species groups, and the role of the Truong Son Range in maintaining the high level of biodiversity over time. PMID- 27394812 TI - Morphology and taxonomy of Isognomon spathulatus (Reeve, 1858), a cryptic bivalve from the mangroves of Thailand. AB - Isognomon spathulatus (Reeve, 1858) is redescribed based on type material and original collections from Kungkrabaen Bay, Thailand. The species agrees with previously described isognomonids in most conchological and anatomical features, but possesses a suite of diagnostic characters, including a comma-shaped outline of the nacreous border, an uncoiled ventral diverticulum of the stomach, and the thickened mantle lobes with granulated cells. This study is the most comprehensive morphological analysis to date for any species of Isognomonidae Woodring, 1925 (1828). It describes and illustrates a number of previously unrecognized or underutilized anatomical characters of potential phylogenetic significance: the morphology of the byssal threads (cross-sectional shape, plumate rootlets, and the shape of adhesive disks), the presence and extent of the interdemibranchial buttresses, the presence of secretory cells in the central zone of the mantle, the shape of the ventral diverticulum of the gastric chamber, the presence of the typhlosolar guard ridge, and the position of the renal pore. A comparison is made between I. spathulatus and morphologically similar Isognomon ephippium (Linnaeus, 1758) with which it has been previously synonymized. Pearls of both species are described and illustrated. Individuals of I. spathulatus inhabit mangroves, where they attach by byssus to prop roots, typically in parapatry with individuals of I. ephippium that occupy adjacent mudflats. The spacial distribution and diverging adaptive strategies (pertaining to physical stabilization and response to predation) displayed by the two isognomonid species are considered in the light of the ecological speciation theory. PMID- 27394813 TI - Revision of Lithosia Fabricius, 1798 and Conilepia Hampson, 1900 (Lepidoptera, Arctiidae). AB - This paper deals with the revision of the Arctiidae genera Lithosia Fabricius, 1798 and Conilepia Hampson, 1900. Only two species currently are considered to be members of Lithosia, Lithosia quadra Linnaeus, 1758, and Lithosia yuennanensis Daniel, 1952. It is here proposed to consider the Far-Eastern populations of L. quadra as subspecies Lithosia quadra dives Butler, 1877, stat. rev. and the Transcaspian populations of the species are described here as Lithosia quadra ssp. soligena ssp. nov. The lectotype of Phalaena Noctua deplana Linnaeus, 1771, preserved in the Hunterian Museum of London, is designated. Two species, Lithosia subcosteola Druce, 1899 and Lithosia gynaegrapha de Joannis, 1930, are excluded from Lithosia. The rare and local Lithosia quadra sikkima Strand, 1922 is raised to species rank and transferred to Conilepia, comb. et stat. nov. The male of C. sikkima is described for the first time. Three species are considered to belong to the genus Conilepia, among them Conilepia cao sp. nov., which is described from Vietnam. All taxa are described and figured. A scenario for the faunogenesis of the Lithosia-Conilepia complex is proposed using molecular data. PMID- 27394814 TI - New Otacilia species from Southwest China (Araneae: Phrurolithidae). AB - The present paper describes nine new Otacilia species from Southwest China: O. mira sp. nov. (?, ?) and O. pyriformis sp. nov. (?, ?) from Chongqing, O. papilion sp. nov. (?, ?) from Guizhou, O. aurita sp. nov. (?, ?), O. digitata sp. nov. (?), O. leibo sp. nov. (?, ?) and O. ovata sp. nov. (?, ?) from Sichuan, O. acuta sp. nov. (?, ?) and O. flexa sp. nov. (?, ?) from Yunnan. Line drawings, photos and descriptions of all new species are presented. In addition, the 21 known Chinese Otacilia species are divided into three species groups. PMID- 27394815 TI - Revision of the genus Campylaimus (Diplopeltidae, Nematoda) with description of four new species from the Sea of Japan. AB - Four new Campylaimus species are described from the deep-sea sediments of the Sea of Japan at depths of about 500-3400 m. Campylaimus orientalis sp. nov. is characterized by having a body of moderate length, clearly annulated cuticle, a small rhomboid mouth opening which is displaced on the dorsal side of body, a gap between the unequal limbs of the amphid, prominent narrow longitudinal alae and cephalated spicules. Campylaimus minutus sp. nov. is characterized by having a cylindrical body, very weak annulations, amphids with a short dorsal limb (25-44% of pharynx length) and a ventral limb completely fused with lateral alae of equal width; and lateral alae extending from the base of the amphid to the tail tip. Campylaimus amphidialis sp. nov. is characterized by having the combination of a very long amphidial fovea occupying nearly the entire length of the pharynx; and a well defined boundary between the ventral amphid limb and lateral alae. The distinctive feature of Campylaimus pulcher sp. nov. is the elongated loop-shaped amphid with nearly equal parallel limbs and prominent narrow longitudinal alae; and cephalated spicules without a gubernaculum. The diagnosis of the genus Campylaimus is emended and an identification key to species, based mainly on form and length of amphidial fovea, width of lateral alae, and copulatory apparatus is given. The genus Campylaimus now includes nineteen valid species. Two species are considered as species inquirendae, mainly because of incomplete descriptions. PMID- 27394816 TI - Revalidation of Triatoma bahiensis Sherlock & Serafim, 1967 (Hemiptera: Reduviidae) and phylogeny of the T. brasiliensis species complex. AB - Triatoma bahiensis Sherlock & Serafim, 1967, T. lenti Sherlock & Serafim, 1967, and T. pessoai Sherlock & Serafim, 1967 were described based on material collected in the Brazilian state of Bahia. These species were later included in the T. brasiliensis complex based on their geographic distribution. Triatoma bahiensis and T. pessoai were subsequently synonymized with T. lenti. However, the phylogenetic position of T. lenti within the T. brasiliensis complex has remained doubtful. This study aims to assess the taxonomic status of T. bahiensis and to infer the phylogenetic relationships between T. lenti, T. bahiensis and the other members of the T. brasiliensis species complex. The identities of the species in concern were confirmed by comparisons with high resolution photos of the respective type materials; lectotypes are designated for T. pessoai and T. bahiensis. Morphological, morphometric, molecular, and cytogenetic approaches as well as experimental crosses were used. The low viability of experimental crosses combined with morphological and morphometric data allow the differentiation of T. bahiensis and T. lenti. Pairwise cyt b sequence divergence between T. lenti and T. bahiensis was 2.5%. Cytogenetic and molecular analyses grouped T. lenti and T. bahiensis as members of the T. brasiliensis complex. These results revalidate the specific status of T. bahiensis. PMID- 27394817 TI - Revision of the grasshopper genus Sedulia Stal, 1878 (Acrididae: Catantopinae) from Malay Peninsula. AB - Southeast Asia is a highly biodiverse region with many species of grasshoppers described since the 19th century. Historical species descriptions are however often not comprehensive and do not meet the modern criteria of taxonomy. Previously used characters for identification need to be re-examined. Here, we aim to revise the taxonomy of the grasshopper genus Sedulia Stal, 1878. Using morphology and simple morphometry, we compared and investigated interspecific and intraspecific variations among the two species of Sedulia. We also redescribed both species and constructed a key to species and closely related genera. PMID- 27394818 TI - The spider genus Cyrioctea Simon on Chanaral Island (Pinguino de Humboldt National Reserve, Atacama, Chile): description of a new species, and the male of Cyrioctea cruz Platnick (Araneae, Zodariidae). AB - A faunistic survey on Chanaral Island, Atacama, near the northern Pacific coast of Chile, allowed the discovery and description of a new species of the spider genus Cyrioctea: C. islachanaral sp. nov., based on females collected by pitfall traps. Strikingly, this new species shares morphological characters with some Southern African representatives of this genus rather than with the species of continental South America. The male of the species C. cruz Platnick, previously known from continental Chile (northern Coquimbo), is described for the first time based on specimens collected in the same locality. PMID- 27394819 TI - A review of Gongylonema spp. (Nematoda: Gongylonematidae) in North American rodents with description of a new species from the cotton rat, Sigmodon hispidus (Mammalia: Cricetidae). AB - Gongylonema archboldi n. sp. (Nematoda: Gongylonematidae) is described from tunnels in the gastric mucosa of the stomach of the cotton rat (Sigmodon hispidus) from Highlands County, Florida, U.S.A. Measurements are also given for specimens from cotton mice (Peromyscus gossypinus), oldfield mice (Peromyscus polionotus), Florida mice (Podomys floridanus), and golden mice (Ochrotomys nuttalli) from the same locality. Additional specimens were collected from the cotton rat and the rice rat (Oryzomys palustris) from Berry Island, San Patricio County, Texas. The new species is differentiated from congeners by a combination of the following characters: length of the left spicule, length and shape of the gubernaculum, distribution of cuticular bosses, length of esophagus, and distance of the vulva from the posterior end. The status of the genus Gongylonema in North American rodents is reviewed. PMID- 27394820 TI - Revision of Urubaxia Fennah (Hemiptera: Cercopidae: Ischnorhininae) with description of two new species. AB - We reviewed Urubaxia Fennah, 1968 and described two new species, Urubaxia solo n.sp. and Urubaxia chewie n.sp. from South America. Species of the genus can be easily distinguished by the shape of the paramere, with two divergent processes, and are usually collected in high altitude zones. An identification key and illustrations are provided. PMID- 27394821 TI - Taxonomic identity of two enigmatic aquatic snake populations (Squamata: Homalopsidae: Cerberus and Homalopsis) from southern Thailand. AB - In their revision of the homalopsid genus Homalopsis Kuhl & Van Hasselt, Murphy et al. (2012) resurrected H. semizonata Blyth, 1855 and noted that ''Frith (1977) reported on two Homalopsis from Phuket, Thailand with 40 and 42 dorsal scale rows, and 159 and 162 ventrals-scale counts within the range of H. semizonata which is found along the same coast, about 900 km to the north''. Murphy et al. (2012), however, did not list H. semizonata from Thailand, and on their species' distribution map they indicated an interrogation mark along the southern coast of Myanmar and the southwestern coast of peninsular Thailand. It should be noted that Murphy et al. (2012) misread Frith: while one of the two specimens reported by Frith was indeed from Phuket (''from the rocky edge of a stream torrent in good forest east of Thalang, central Phuket Island''), the other was from ''Klong Nakha, 80 kilometeres [sic] south of Ranong in lowland rain forest with some clearings and dwellings'', thus in Ranong Province, closer to the border with Myanmar. Nabhitabhata et al. (2004) recognized a single Homalopsis species in Thailand, H. buccata, which they listed for numerous provinces, including Phuket, based on Frith's (1977) record. Among the two Homalopsis species recognized to occur in Thailand by Nabhitabhata and Chan-ard (2005), H. buccata and H. nigroventralis, none was recorded by them from Phuket Province, but H. buccata was listed from, among others, the neighbouring provinces of Phang-Nga and Ranong. Chuaynkern & Chuaynkern (2012) recognized the same two species, and listed H. buccata from, among others, the provinces of Phang-Nga, Phuket and Ranong. Cox et al. (2012) listed three Homalopsis for Thailand (H. buccata, H. mereljcoxi and H. nigroventralis), and indicated that H. mereljcoxi is the species occurring, a.o., in Phang-Nga, Phuket and Ranong provinces. Wallach et al. (2014) noted that H. semizonata lives in southern Myanmar near sea level, but also that it ''possibly occurs in Phuket''. Chan-ard et al. (2015), in their field guide whose reptile taxonomy is largely outdated (Pauwels & Grismer 2015), recognized only Homalopsis nigroventralis and H. buccata and the map for the latter indicates its presence in Phuket and Phang-Nga provinces. In the most recent synthesis on the family Homalopsidae, Murphy & Voris (2014) made however no mention of the possibility that H. semizonata occurs in Thailand. Because of the lack of voucher material, the identity of the Homalopsis living on the Indian Ocean coastal area of Thailand has thus remained poorly understood so far. PMID- 27394822 TI - Epibiotic rotifers of Gammarus pulex (L.) (Crustacea, Amphipoda), with descriptions of two new species and notes on the terminology of the trophi. AB - The epibiotic rotifers of a Gammarus pulex (L.) collection from the Ardeche, France are reported. Four species were found, of which Cephalodella jersabeki n. sp. and Proales gammaricola n. sp. are new to science and described. The other species, Dicranophorus cambari Wulfert and Embata laticeps (Murray), are commented upon. SEM micrographs of the trophi are presented, and a new or amended terminology is proposed for some diagnostic trophi parts. PMID- 27394823 TI - A remarkable new species of the magnus species-group of Cryptocellus (Arachnida, Ricinulei) from Ecuador, with observations on the taxonomy of the New World genera. AB - A new ricinuleid species, Cryptocellus chimaera sp. nov., is described based on a male specimen from Northwest Ecuador (Esmeraldas, Reserva Ecologica Mache Chindul, Estacion Biologica Bilsa). This species is unique among all Cryptocellus in having very large longitudinal carapacial translucent areas together with a markedly incrassate femur of leg II. Representing only the second species of the order described from Ecuador, C. chimaera sp. nov. is assigned to the magnus species-group of Cryptocellus Westwood, 1874. Cryptocellus chimaera sp. nov. is remarkable, for its morphology resembles that of Cryptocellus magnus Ewing, 1929, especially with regard to the male copulatory apparatus, although both resemble Pseudocellus Platnick, 1980, due to the presence of diffuse longitudinal carapacial translucent areas. Along with the new species description, a comparative diagnosis and supplementary images are provided for C. magnus. Based on direct observations of some species belonging to the five species-groups of Cryptocellus, we discuss on the occurrence of different morphologies of carapacial translucent areas within the genus. We deem it important to continue the survey of morphological characters, especially within Cryptocellus, in order to increase our understanding of the species-groups and to unravel their relationships. PMID- 27394824 TI - Reconciling more than 150 years of taxonomic confusion: the true identity of Moenkhausia lepidura, with a key to the species of the M. lepidura group (Characiformes: Characidae). AB - Moenkhausia lepidura (Kner) is redescribed based on the examination of the type and other specimens from several localities of the Amazon and Orinoco basins. The species is readly diagnosed from congeners by a combination of a dark blotch on the upper caudal-fin lobe, lower lobe hyaline, and by the arrangement of predorsal scales, in which scales of anterior portion of predorsal area are arranged in pairs, followed by a single median row of scales extending to dorsal fin origin. The analysis of the type material of Gymnotichthys hildae Fernandez Yepez and Knodus calliurus Ahl demonstrated the former is a junior synonym of Moenkhausia lepidura, whereas the latter should be removed from its synonymy. An identification key to the Moenkhausia lepidura-group is provided. PMID- 27394825 TI - Recognizing Panulirus meripurpuratus sp. nov. (Decapoda: Palinuridae) in Brazil Systematic and biogeographic overview of Panulirus species in the Atlantic Ocean. AB - Genetic analysis divides Panulirus argus into two different species, physically separated by the Amazon-Orinoco plume since the Last Glacial Maximum. Panulirus argus sensu stricto is distributed north of this biogeographic barrier and the second species to the south, occurring in Brazil. The Panulirus species in the Atlantic Ocean are being overfished and the standing stocks are unknown and still not considered endangered or threatened due to a deficiency of precise abundance data. The lack of data makes it impossible to undertake an effective conservation and management policy. In order to assist in the future management and conservation of the Spiny Lobster in the Atlantic Ocean and particularly for the indigenous species from Brazilian waters, this study formally recognizes and describes a new species, Panulirus meripurpuratus sp. nov., for what was previously known as P. argus in Brazilian waters, and differentiates it from Panulirus argus from North American waters and the Caribbean Sea. The work also presents an overview of the biogeographic distribution of the species and presents two identification keys to Atlantic species, one based on morphology and the other on live colouration. PMID- 27394826 TI - Phylogenetic relationships of geckos of the Hemiphyllodactylus harterti group, a new species from Penang Island, Peninsular Malaysia, and a likely case of true cryptic speciation. AB - An integrative taxonomic analysis based on the mitochondrial gene ND2 and its flanking tRNAs, morphology, and color pattern indicates that a newly discovered gecko described herein as Hemiphyllodactylus cicak sp. nov. from Penang Hill on the Island of Penang, Peninsular Malaysia is a member of the H. harterti group. Hemiphyllodactylus cicak sp. nov. is most closely related to the clade composed of the sister species H. harterti from Bukit Larut, Perak in the Bintang Mountain Range and H. bintik from Gunung Tebu, Terengganu from the Timur Mountain Range. These three allopatric species form a monophyletic group that extends approximately 270 km across three isolated mountain ranges in northern Peninsular Malaysia. The molecular analysis also indicates that H. titiwangsaensis from the Titiwangsa Mountain Range is composed of three genetically distinct allopatric populations. The southern two populations from Fraser's Hill and Genting Highlands, Pahang have an uncorrected pairwise sequence divergence of 3.5% whereas these two populations have 12.4 and 12.8 % sequence divergences, respectively, from the northern population at Cameron Highlands, Pahang. Although the high sequence divergence clearly distinguishes the southern two populations from the former as a different species, all three populations are morphologically indistinguishable, leading to the hypothesis of a true, cryptic speciation event. PMID- 27394827 TI - Description of a new species of Pareiorhina (Siluriformes: Loricariidae) from the rio Sao Francisco basin, Brazil. AB - In the present paper we describe a new species of Pareiorhina from Minas Gerais State, Brazil. The new species is distinguished from its congeners by a combination of the following characters: the dorsal surface of caudal peduncle strongly concave, 30 vertebrae, bicuspid teeth, a conspicuous cylindrical shaped papilla between the oral valve and premaxilla, smaller odontodes along the snout margin, a small orbital diameter, a higher head width, a shorter interorbital width, a shorter predorsal length, a shorter cleithral width, and a shorter caudal peduncle depth. The new species is known from four small streams of the rio Sao Francisco basin: one tributary of the rio Maranhao, one tributary of the rio Paraopeba and two tributaries of the Rio das Velhas. This species is found in fast-flowing streams associated with rocks and sand in the bottom of the rivers. PMID- 27394828 TI - Studies of Peruvian Ptiliidae (Coleoptera) 4: Peruvium a new subgenus of Ptenidium with seven new species. AB - Peruvium a new subgenus of Ptenidium Erichson with seven new species: P. brevissimum sp. n.; P. carinatum sp. n.; P. capillatum sp. n.; P. contractum sp. n.; P. gibbosum sp. n.; P. inornatum sp. n. and P. grande sp. n. is described and figured. The insects were collected by Dr Caroline Chaboo and her students at the University of Kansas as part of a programme to compile an inventory of leaf beetles in Peru and are the first records of Ptenidium from the country. A key is provided. PMID- 27394829 TI - Discovery of a fourth species of Shaanxiana (Lepidoptera: Lycaenidae: Theclinae) from China. AB - Shaanxiana langi sp. n. (Theclinae: Theclini), a fourth species of the genus Shaanxiana, is described from Guangxi province, China. It is similar to the recently described S. australis from Guangdong, but S. langi males can be distinguished from the latter by their lack of orange scales within the underside submarginal wing markings, and the medially protruding uncus of the genitalia. The female is notable for its extensive pale blue upperside wing coloration, requiring re-characterization of the genus with respect to sexual dimorphism. Both male and female genitalia of S. langi sp. n. are illustrated and described in detail, together with S. takashimai. PMID- 27394830 TI - A redescription of Culicoides griseidorsum Kieffer, 1918, with comments on subgeneric position of some European taxa (Diptera: Ceratopogonidae). AB - Culicoides griseidorsum Kieffer, 1918 is formally redescribed, and the male described and illustrated for the first time. The species is placed within Sensiculicoides Shevchenko, 1977 the subgenus restored from the synonymy with Oecacta Poey, 1853. A checklist of European species placed in subgenera Sensiculicoides and Oecacta is provided. PMID- 27394831 TI - Three new species and a new record of Smicridea McLachlan 1871 (Trichoptera: Hydropsychidae) from Minas Gerais state, Brazil. AB - Three new species of Smicridea McLachlan 1871 are described and illustrated based on specimens collected in Parque Nacional da Serra da Canastra and its surrounding area, Minas Gerais state, southeastern Brazil. Smicridea (Rhyacophylax) necator sp. nov. possibly belongs to the S. (R.) dispar Group, but its placement in this group is weakly supported; S. (Smicridea) franciscana sp. nov. belongs to the S. (S.) nigripennis Group based on morphology of the phallus; S. (S.) sepala sp. nov. is a member of the S. (S.) fasciatella Group, also based on the morphology of the phallus. A new record of S. (S.) sattleri Denning & Sykora 1968 is provided for Minas Gerais state, Brazil. PMID- 27394832 TI - A new species of cardinalfish (Gymnapogon, Gymnapogonini, Apogonidae, Percomorpha) from the Philippines. AB - The new species is consistent with Gymnapogon, a distinct genus having one to three spines on the preopercle edge, fused hypurals (parhypural+1+2 and 3+4+terminal central), a free fifth hypural, two epurals, no supraneurals, scaleless head and body, a single rod-like postcleithrum and complex lines of free neuromasts on the head, body and caudal fin. The new species is distinguished by having a combination of a rounded caudal with 15 branched principal caudal-fin rays, 2 unbranched principal caudal-fin rays, 10 soft dorsal rays with the anterior two rays unbranched, 9 or 10 anal rays with the first ray unbranched and 14 pectoral rays the lower three and upper two unbranched. Nominal species Gymnapogon annona, G. foraminosus, G. japonicus, G. urospilotus and G. vanderbilti have 9 or 10 soft dorsal, 9 or 10 anal rays and 12 to 14 pectoral rays, the lower two and upper two unbranched. Gymnapogon africanus, G. melanogaster and G. philippinus have 9 soft dorsal rays, the first ray unbranched and 8 soft anal rays, the first ray branched. Gymnapogon japonicus has a rounded caudal fin with 13, 14 or 15 branched principal caudal rays. Gymnapogon africanus, G. annona, G. melanogaster, G. philippinus, G. urospilotus and G. vanderbilti have a forked caudal fin with 13 branched principal caudal rays and 2 unbranched upper and lower principal caudal rays. A single preopercle spine distinguishes the new species from the single bifid-like preopercle spine shared by Gymnapogon annona, G. melanogaster and undescribed forms. The wide-spread B marked species complex made up of Gymnapogon urospilotus, G. vanderbilti and undescribed forms have at least one small upper preopercle spine in addition to the larger single spine near the angle of the preopercle. PMID- 27394833 TI - Phlugis ocraceovittata and its ultrasonic calling song (Orthoptera, Tettigoniidae, Phlugidini). AB - Some observations on the small predatory katydid Phlugis ocraceovittata Piza 1960 from southern Brazil are presented. A male was calling both day and night, producing long uniformly structured sequences with maximum energy between 40 and 60 kHz. According to anecdotal and indirect evidence the species is not exclusively predacious and can live partly also on vegetable food. PMID- 27394834 TI - Transferred depository for twenty-seven holotypes of the plant bug and flower bug species recently described from Thailand (Hemiptera: Heteroptera: Miridae and Anthocoridae). AB - Between 2010 and 2013, twenty-six plant bug (Miridae) and one flower bug (Anthocoridae) species were described from Thailand by Yasunaga, Yamada and their colleagues. The original description of each species stated that the holotype depository was 'SUT' (Suranaree University of Technology, Nakhon Ratchasima, Thailand). Because continuous maintenance for type specimens in SUT would become difficult, with the consent of SUT, we have transferred the depository for each of the following holotype specimens from SUT to 'DOAT' (Insect Collection, Entomology & Zoology Group, Plant Protection Research and Development Office, Department of Agriculture, Bangkok). Accordingly, we herein provide the necessary information on each holotype specimen to properly satisfy 'Recommendations 16C and 72F' of the International Commission of Zoological Nomenclature (ICZN, 1999). PMID- 27394835 TI - First description of the male Hoedillus sexpunctatus Simon, 1898; a redescription of the female, and transfer of Hoedillus to Zoropsidae Bertkau, 1882 (Araneae). AB - Hoedillus sexpunctatus Simon, 1898 was described from a single female specimen collected in Guatemala and is the type species of the monotypic genus Hoedillus Simon, 1898. This genus was originally placed in the family Sparassidae Bertkau, 1872, subfamily Heteropodinae Thorell, 1873. In a review of this subfamily, Jager (2002) determined that Hoedillus was misplaced in Sparassidae due to the lack of metatarsal trilobate membranes. Hoedillus was transferred to the family Zoridae Pickard-Cambridge, 1893 by Jager (2002), now a junior synonym of Miturgidae Simon, 1886 (Ramirez 2014). Ramirez (2014), suggested Hoedillus may be a member of the Xenoctenus group, but provisionally listed it as a Miturgidae, awaiting further investigation. PMID- 27394836 TI - Description of two new and six known species of the genus Tylencholaimus de Man, 1876 (Nematoda: Dorylaimida) with a diagnostic compendium and key to species. AB - Two new and six known species of the soil-inhabiting nematode genus Tylencholaimus de Man, 1876 are described and illustrated. Tylencholaimus arakii sp. n. is characterized by having 0.56-0.65 mm long body; lip region cap-like, set off by a shallow constriction; labial disc present; odontostyle 7-8 um and odontophore 7-8 um long, with well-developed, asymmetrical basal knobs; total spear length 15 MUm; pharynx with slender anterior part which expands abruptly into the cylindrical basal bulb occupying about 45-47% of total neck length; female genital system mono-prodelphic; transverse vulva and short, hemispheroid tail. Tylencholaimus ladakhiensis sp. n. is characterized by having 0.56-0.73 mm long, slender body; lip region cap-like, set off by a slight constriction; amphid aperture slit-like; odontostyle slender 7-9 um, with comparatively narrow lumen, odontophore 8-9 um long; pharynx with slender anterior part which expands abruptly into the cylindrical basal bulb, occupying about 38-45% of total neck length; female genital system didelphic-amphidelphic and rounded-conoid tail, with distinct terminal caudal pore. Tylencholaimus proximus Thorne, 1939; Tylencholaimus mongolicus Andrassy, 1967; Tylencholaimus vulvulatus Rahman, Jairajpuri, Ahmad & Ahmad, 1987; Tylencholaimus ibericus Pena-Santiago & Coomans, 1994; Tylencholaimus imperanus Mohilal & Dhanachand, 2003 and Tylencholaimus cosmos (Dhanam & Jairajpuri, 1999) Pena-Santiago, 2008 are redescribed. Tylencholaimus proximus and Tylencholaimus mongolicus are reported for the first time from India and a male is reported for the first time for T. imperanus. A diagnostic key and compendium to species of the genus Tylencholaimus is provided. PMID- 27394837 TI - A new subgenus Oculogaster subgen. n. for viviparous representatives of Procloeon s. l., with discussion about status of the generic name Austrocloeon Barnard 1932 and the species name africanum Esben-Petersen 1913 [Cloeon] (Ephemeroptera, Baetidae). AB - A new subgenus Oculogaster subgen. n. is established in the genus Procloeon Bengtsson 1915. It is characterized by viviparity and constant presence of one vein in pterostigma. Widely distributed African species Procloeon (Oculogaster) cylindroculum Kimmins 1956 is redescribed based on male and female imagoes reared from larvae in Zambia and Uganda. A new species Procloeon (Oculogaster) album sp. n. is described based on reliably associated larvae, subimagoes and imagoes of both sexes from Thailand. Status of the generic name Austrocloeon Barnard 1932 and the species name Cloeon africanum Esben-Petersen 1913 are discussed, and the nominal species C. africanum is fixed as the type species of the genus-group name Austrocloeon; according to this type fixation, the binomen Austrocloeon africanum belongs to a species of the subfamily Rhithrocloeoninae. PMID- 27394838 TI - Redescription Cyrtodactylus lateralis (Werner) (Squamata: Gekkonidae) and Phylogeny of the Prehensile-tailed Cyrtodactylus. AB - We redescribe Cyrtodactylus lateralis (Werner) on the basis of new specimens. Cyrtodactylus lateralis is a prehensile-tailed species, known from scattered lowland to mid-elevation localities in northern Sumatra. The prehensile-tailed Cyrtodactylus are more speciose and have a wider distribution than previously thought. This group includes a mainland SE Asian clade consisting of C. elok, C. interdigitalis, and C. brevipalmatus and an insular clade containing C. durio, C. lateralis, C. nuaulu, C. serratus, C. spinosus, and C. stresemanni. However, a distinctive color pattern in the Wallacean and Papuan species and uncertainty surrounding the type locality of C. stresemanni raise unresolved questions about the inclusiveness of the insular clade. DNA sequence data supports a close relationship between C. elok and C. interdigitalis, but also reveals that C. lateralis and C. durio are not closely related to these species. PMID- 27394839 TI - Grammedessa, a new genus of Edessinae (Hemiptera: Heteroptera: Pentatomidae). AB - The new genus Grammedessa is here proposed for 12 species: Edessa pallicornis, E. bugabensis, E. rorativentris and E. stillativentris, and eight new species: Grammedessa brunneotarsata, G. polytreta, G. flavolimbata, G. paraensis, G. braziliana, G. hypsolineata, G. multicavata and G. matogrossensis. Species belonging to this genus share four black punctured longitudinal stripes on the dorsal surface of the head; humeral angles laterally projected and slightly flattened dorso-ventrally; metasternal process with branches of anterior bifurcation narrow, long, and with acute apices; abdominal trichobothria placed laterally, not aligned with spiracles; females with gonocoxites 8 and laterotergites 8 always punctured, gonocoxites 8 large, subequal in length to laterotergites 9; males with ventral rim of pygophore deeply excavated, superior process of genital cup partially fused to the wall. Edessa strigiceps is considered a junior synonym of Grammedessa pallicornis n. comb.. Males of Grammedessa bugabensis n. comb. and Grammedessa rorativentris n. comb. are described for the first time. New distribution records of Grammedessa bugabensis, Grammedessa rorativentris, and Grammedessa stillativentris n. comb. is extended. The lectotype of Edessa bugabensis is herein designated. PMID- 27394841 TI - New South American species of Cerambycinae, and notes on Corimbion balteum Martins (Coleoptera, Cerambycidae). AB - Three new species of Cerambycinae are described from South America: Mecometopus hauseri (Clytini), from Bolivia; Cycnoderus (Cycnoderus) metallicus (Rhopalophorini), from Venezuela; and Corimbion mutabile (Neoibidionini), from Ecuador. Mecometopus hauseri and Corimbion mutabile are included in previous keys. Corrections to the original description of Corimbion balteum Martins, 1970 are presented. PMID- 27394840 TI - A new species of Neotropical freshwater stingray (Chondrichthyes: Potamotrygonidae) from the Rio Negro, Amazonas, Brazil: the smallest species of Potamotrygon. AB - A new species of Potamotrygon is described from the Rio Negro drainage, Amazonas, Brazil. In spite of being cited or pictured several times in the scientific and aquarium fish literature since the 19th Century, it had been misidentified and still lacked a scientific name. Potamotrygon wallacei, n. sp., is diagnosed by the following characters: dorsal surface of disc light brown, with black irregularly-shaped vermiculate markings forming an amphora- or Omega-shaped figure on mid-disc, delimiting light brown reniform areas at disc center, and with subcircular light brown ocellate markings on disc margins; small body size (smallest known Potamotrygon species; largest examined specimen measured 310 mm DW); dorsal spines on tail usually rather low, without broad bases, in one to rarely three irregular rows, but extending posteriorly only to tail mid-length and not to caudal stings, with altogether relatively few spines; denticles on posterior mid-disc and tail base Y-shaped, with a central, anterior, bulbous cusp and usually two posterior pairs of smaller, rounded cusps; and single (anterior) angular cartilage. The new species is similar to P. orbignyi and other "reticulated" species in having a single (anterior) angular cartilage and in the color pattern of the tail, but is easily distinguished based on its size, dorsal tail spine arrangement, and specific details of color pattern. PMID- 27394842 TI - The advertisement and aggressive calls of Rhinella abei (Baldissera, Caramaschi, and Haddad, 2004) (Anura: Bufonidae) from Campo Largo, Parana, Brazil. AB - Rhinella abei is a medium-sized species (snout-to-vent length 57.0-76.4 mm in males; 60.4-83.9 mm in females-Baldissera et al. 2004) of the Rhinella crucifer species group, distributed in the Brazilian Atlantic Rainforest, from the State of Parana to northern Rio Grande do Sul (Frost 2016). It is recorded in forested areas (Conte & Rossa-Feres 2007), or while breeding along forest edges and open habitats. Information on advertisement calls of species in the R. crucifer group is available for R. casconi, R. crucifer, R. inopina and R. ornata (Andrade et al. 2015; Heyer et al. 1990; Oliveira et al. 2014; Roberto et al. 2014). Here we describe the advertisement and aggressive calls of R. abei recorded in the municipality of Campo Largo (25.507472 degrees S, 49.376632 degrees W, datum "WGS84"), southeast State of Parana, Brazil. PMID- 27394843 TI - Nomenclatural note on the homonymy between the octocoral genus Dendrobrachia Brook 1889 and the entoproct phylum Dendrobrachia Xian-Guan, Bergstrom, Xio-Ya and Jie 2006. AB - Dendrobrachia was proposed by Xian-Guan et al. (2006) as the name of a new phylum of entoproct-like animals from the Lower Cambrian (Yunnan Province, China). This name was however preoccupied by the octocoral Dendrobrachia Brook 1889, which position within the subclass Octocorallia is currently uncertain (Opresko and Bayer 1991; Berntson et al. 1999, 2001). Based on the principles of homonymy and priority (Articles 52 and 23, respectively; ICZN 1999), a substitute name for the entoproct Dendrobrachia is necessary, and I propose Dendrobrachion (based on the Greek brachion, for arm). PMID- 27394844 TI - Replacement names for Chapinia and Ripleyia (Aves: Passeriformes: Muscicapidae). AB - Earlier this year, two of us (GV & RB) introduced the genus-group names Chapinia and Ripleyia (in Voelker et al. 2016) for two species of African flycatchers allied to Muscicapa. We recently became aware that both of these genus-group names are preoccupied within Animalia (Chapinia by Chapinia Ewing, 1927 [Insecta: Phthiraptera] and Ripleyia by Ripleyia Cossman, 1920 [Mollusca]), rendering them junior homonyms. Following Article 60 of the International Code of Zoological Nomenclature (ICZN 1999) we herein provide replacement names for the two generic names introduced in Voelker et al. (2016). PMID- 27394845 TI - MATTHEW H. VAN DAM & CHARLES W. O'BRIEN (2015) Review of the genus Miloderes Casey, 1888 (Coleoptera: Curculionidae: Entiminae), with desciptions of three new species. Zootaxa, 4006 (2): 247-284. PMID- 27394846 TI - Morphology and identification of the mature larvae of several species of the genus Otiorhynchus (Coleoptera, Curculionidae, Entiminae) from Central Europe with an update of the life history traits. AB - The mature larvae of 14 Otiorhynchus taxa are described: O. (Otiorhynchus) armadillo (Rossi, 1792), O. (Nehrodistus) armatus Boheman, 1846, O. (Otiorhynchus) aurifer Boheman, 1843, O. (Pocodalemes) crataegi Germar, 1824, Otiorhynchus (Arammichnus) indefinitus Reitter, 1912 (syn. O. dieckmanni Magnano, 1979), O. (Choilisanus) raucus (Fa-bricius, 1777) and 3 taxa of the O. (Otiorhynchus) tenebricosus complex (Herbst, 1784), O. (Otiorhynchus) clavipes (Bonsdorff, 1785), O. (Otiorhynchus) fuscipes (Olivier, 1807) and O. (Otiorhynchus) lugdunensis Boheman, 1843, are described and illustrated for the first time. The larvae of (Otiorhynchus) meridionalis Gyllenhal, 1834, O. (Pendragon) ovatus (Linnaeus, 1758), O. (Zustalestus) rugosostriatus (Goeze, 1777), O. (Metopiorrhynchus) singularis (Linnaeus, 1767), and O. (Dorymerus) sulcatus (Fabricius, 1775) are redescribed and illustrated, and new characters are added. Important characters of the mature larvae (e.g. chaetotaxy, shape of head and body) are explained in detail and illustrated. A key to the identification of the mature larvae of 19 Otiorhynchus taxa is provided. Breeding and collecting data of the larvae are given, and the study is completed by a current overview on the life histories of all treated species. PMID- 27394847 TI - On a collection of Batraxis Reitter (Coleoptera: Staphylinidae: Pselaphinae) from Hainan Island, southern China. AB - Seven species of the genus Batraxis Reitter are described from Hainan Island, southern China: B. bicolor Wang & Yin, sp. n., B. tibialis Wang & Yin, sp. n., B. pilosus Wang & Yin, sp. n., B. spinosus Wang & Yin, sp. n., B. hainanensis Wang & Yin, sp. n., B. minor Wang & Yin, sp. n., and B. simplex Wang & Yin, sp. n. Keys to both sexes of these Batraxis are provided. PMID- 27394848 TI - Blackflies (Diptera: Simuliidae) in Croatia: species richness, distribution and relationship to surrounding countries. AB - All records of blackflies (Simuliidae) from the territory of Croatia are summarized, including previously unpublished data. The blackfly fauna of Croatia consists of 28 species. Simulium (Nevermannia) angustitarse (Lundstrom), Simulium (Nevermannia) cryophilum (Rubtsov) complex, Simulium (Nevermannia) lundstromi (Enderlein), Simulium (Nevermannia) vernum Macquart complex, Simulium (Simulium) argyreatum Meigen, Simulium (Simulium) bezzii (Corti) complex, Simulium paraequinum Puri and Simulium pseudequinum Seguy are reported for the first time from Croatia. Information related to the ecoregions, in which species were found and specific species traits are given. Genus Prosimulium Roubaud is represented by one species only. Genus Simulium Latreille is represented by 27 species in six subgenera, with subgenus Simulium Latreille s. str. being most species rich (13 species) and subgenera Boophthora Enderlein and Trichodagmia Enderlein represented each by only one species. Compared to the neighboring countries, the Croatian species assemblage is most similar to the fauna of Slovenia and least similar to that of Italy. The relatively low number of species, presence of several species complexes and unclear identity of other species show that further research of blackflies in Croatia is needed. PMID- 27394849 TI - Morphometric and preliminary genetic characteristics of Branchinecta orientalis populations from Iran (Crustacea: Anostraca). AB - Branchinecta orientalis is a fairy shrimp endemic to the Palearctic region, from Mongolia to Spain. The patchy nature of its habitat is thought to result in a high degree of subdivision among populations, potentially promoting speciation. We combined morphometric characteristics with molecular phylogeny of cytochrome c oxidase I (COI) to test whether B. orientalis could be a species complex and whether there is any correlation between the genetic variation, morphometric characteristics and geographical variables. We studied six populations from Iran based on the comparison of morphometric and molecular datasets, we confirmed that the Aigher Goli (AIG) population is biometrically well separated from the Akh Gol, Hassar, Rashakan, Khaslou and Garagojanlou populations in northwestern Iran. The relatively high genetic divergence in the AIG from the other populations and its congruence with morphometric data were observed in B. orientalis populations. However, as these results were generated using a small sample size and on a limited sampling range, they should be considered as preliminary. PMID- 27394850 TI - Contribution to the Chinese subfamily Rhaphidophorinae Walker, 1869 (Orthoptera: Rhaphidophoridae; Rhaphidophorinae): New additions to the genera Eurhaphidophora and Stonychophora. AB - A key to the genera of Rhaphidophorinae is present. One new species of Eurhaphidophora, E. truncata Bian & Shi sp. nov., and the female sex of E. visibilis Gorochov, 2010 are described from China. Meanwhile, Stonychophora is recorded for the first time in the Chinese fauna and a new species viz., Stonychophora hainanensis, is described from Hainan. The voucher material is deposited in the Museum of Hebei University. PMID- 27394851 TI - A new Bent-toed gecko (Squamata: Gekkonidae) from the Mekongga Mountains, South East Sulawesi, Indonesia. AB - We describe Cyrtodactylus hitchi sp. nov., a new species of Bent-toed Gecko from montane forests in the Mekongga Mountains, South East Sulawesi, Indonesia. Although we cannot speculate about relationships, morphologically it shares several traits with C. batik, a large species known only from Mount Tompotika near the tip of Sulawesi's Eastern Peninsula. The following unique combination of characters distinguishes it from all other congeners: absence of precloacal groove, absence of precloacal and femoral pores, absence of enlarged femoral scales, no abrupt contact between large and small postfemoral scales, 18-20 lamellae under the fourth toes, and transversely enlarged, median subcaudal scales arranged in a single row. PMID- 27394852 TI - Description of a new species of crested newt, previously subsumed in Triturus ivanbureschi (Amphibia: Caudata: Salamandridae). AB - Multilocus molecular data play a pivotal role in diagnosing cryptic species (i.e. genetically distinct but morphologically similar species). A multilocus phylogeographic survey has provided compelling evidence that Triturus ivanbureschi sensu lato comprises two distinct gene pools with restricted gene flow. We conclude that this taxon had better be treated as two distinct (albeit morphologically cryptic) species. The name T. ivanbureschi should be restricted to the western species, which is distributed in western Asiatic Turkey plus the south-eastern Balkan Peninsula. No name is as yet available for the eastern species, which is distributed in northern Asiatic Turkey. We propose the name T. anatolicus sp. nov. for the eastern species and provide a formal species description. PMID- 27394853 TI - Loboschiza Diakonoff (Lepidoptera: Tortricidae) from Thailand with descriptions of four new species. AB - Four new species of Loboschiza Diakonoff collected from the Nakhon Ratchasima, Chanthaburi, Nakhon Nayok, Sa Kaeo, Nakhon Si Thammarat, and Nakhon Pathom provinces of Thailand are described: Loboschiza spiniforma Anan and Pinkaew, n. sp.; Loboschiza bisulca Anan and Pinkaew, n. sp.; Loboschiza subrectangula Anan and Pinkaew, n. sp.; and Loboschiza lunata Anan and Pinkaew, n. sp. Loboschiza koenigiana (Fabricius) is redescribed. Illustrations of adults and genitalia are provided. PMID- 27394854 TI - Redescription of Chilenoperla puerilis (Gripopterygidae: Plecoptera) from the eastern Andes of Patagonia. AB - The male and the last instar larva of Chilenoperla puerilis Illies (Gripopterygidae) are redescribed from Chubut Province, Argentinean Patagonia. Wing venation previously not described, differs from other described species in the genus. The larva is separable from that of C. elongata Vera and C. puelche Vera. Comments on the generic and specific position of the material studied and similarities and differences among the genera Chilenoperla Illies and Pelurgoperla Illies are included. Until new systematic and phylogenetic evidence becomes available no taxonomic changes are proposed. PMID- 27394855 TI - Solariella quadricincta Quinn, 1992 and S. staminea Quinn, 1992 are synonyms of S. carvalhoi Lopes & Cardoso, 1958 from the SW Atlantic (Gastropoda: Solariellidae). AB - Solariellidae is a diverse family of small (5-20 mm) marine snails of worldwide distribution. They usually live on fine sediment to unconsolidated substrates in deep-waters of extra-tropical to tropical latitudes (Hickman 1998; Williams et al. 2013). Initially described as a subfamily of Trochidae, it has been recently raised to family level (Bouchet et al. 2005; Williams et al. 2008). The evolutionary relationships among solariellids have been extensively investigated in the light of morphological and molecular data, but the family still lacks a comprehensive taxonomic revision that reflects recent discoveries (Williams et al. 2010, 2013). The family's fossil record possibly dates back to the Campanian of Torallola, Spain (Kiel & Bandel 2001; Williams et al. 2013). PMID- 27394856 TI - A phylogeny of Astyanax (Characiformes: Characidae) in Central and North America. AB - A phylogeny is presented for 34 species of Astyanax, 27 of them once included within A. aeneus or A. fasciatus in Central America and Mexico, based on 52 morphological characters (mostly osteological, but also pigmentation and meristics), with three outgroups. Monophyly is not supported for A. aeneus s. lat., as Brazilian species such as A. fasciatus s. str. and others occur also within that clade. There were only five resolved clades, three of them including both Brazilian and Central American species, one purely Nicaraguan, and one for central-northern Mexico and Texas. Coincidence with previous cladistic hypotheses is only partial. The genus Bramocharax Gill is not recovered, and thus confirmed as a synonym of Astyanax Baird & Girard. The findings point at a more complex biogeographic history of the region than usually recognized. PMID- 27394857 TI - On the systematic position of some species of Chiloneus, Desbrochersella and Sciaphilus, with description of two new species and lectotype selection (Coleoptera: Curculionidae: Entiminae). AB - Chiloneus globulus sp. nov. and C. tenietensis sp. nov. from Algeria are described, illustrated and compared with closely related species. The following new combinations are proposed: Chiloneus barbaricus (Gonzalez, 1970) from Desbrochersella, Chiloneus innotatus (Pic, 1927) from Sciaphilus, Desbrochersella diversepubens (Pic, 1904) and Desbrochersella microps (Desbrochers des Loges, 1897) from Chiloneus, Myochlamys convexiceps (Desbrochers des Loges, 1896), Polydrusus (Leucodrusus) henoni (Allard, 1869) and Sericopholus murinus (Desbrochers des Loges, 1896) from Chiloneus. The following new synonymies are proposed: Chiloneus alboscutellaris (Pic, 1917) as a junior synonym of Chiloneus submaculatus (Pic, 1917), Chiloneus curtipennis (Pic, 1917) as a junior synonym of Desbrochersella diversepubens (Pic, 1904), Chiloneus dividuus (Pic, 1904) as a junior synonym of Chiloneus pennatus (Faust, 1885), Chiloneus inhumeralis (Pic, 1903) as a junior synonym of Chiloneus chobauti (Desbrochers des Loges, 1897), Chiloneus nasutus (Desbrochers des Loges, 1897) as a junior synonym of Chiloneus pertusicollis (Fairmaire, 1868), Chiloneus nitens (Pic, 1904) as a junior synonym of Chiloneus cinerascens (Rosenhauer, 1856), Chiloneus insulanus (Gonzalez, 1970) as a junior synonym of Chiloneus innotatus (Pic, 1927), Chiloneus pilosulus Normand, 1953 as a junior synonym of Chiloneus vaulogeri (Pic, 1896), Chiloneus ruficornis (Allard, 1869) as a junior synonym of Chiloneus pertusicollis (Fairmaire, 1868), Chiloneus seminitidus (Hustache, 1941) as a junior synonym of Chiloneus cinerascens (Rosenhauer, 1856), Chiloneus subannulipes (Pic, 1917) as a junior synonym of Chiloneus minutissimus (Pic, 1904), Chiloneus subglobatus (Desbrochers des Loges, 1892) as a junior synonym of Chiloneus chevrolati Tournier, 1874, Chiloneus theresae (Pic, 1945) as a junior synonym of Chiloneus brevithorax Desbrochers des Loges, 1874, Chiloneus tuniseus (Desbrochers des Loges, 1897) as a junior synonym of Chiloneus brevipilis Desbrochers des Loges, 1893, Desbrochersella nitidipennis Pic, 1927 as a junior synonym of Chiloneus minutissimus (Pic, 1904), Pleurodirus alluaudi (Pic, 1903) as a junior synonym of Chiloneus vaulogeri (Pic, 1896), Sericopholus triangulifer (Desbrochers des Loges, 1903) as a junior synonym of Sericopholus murinus (Desbrochers des Loges, 1896). Lectotypes of the following species are designated (current names added in brackets when different): Alophinus triangulifer Desbrochers des Loges, 1903 (currently Sericopholus murinus (Desbrochers des Loges, 1896)), Alophinus triangulifer v. subuniformis Pic, 1904 (currently Sericopholus murinus (Desbrochers des Loges, 1896)), Chiloneus algericus Desbrochers des Loges, 1871 (currently Chiloneus infuscatus (Chevrolat, 1861)), Chiloneus brevi-pilis Desbrochers des Loges, 1893, Chiloneus carinidorsum Desbrochers des Loges, 1871, Chiloneus chevrolati Tournier, 1874, Chiloneus murinus Desbrochers des Loges, 1896 (currently Sericopholus murinus (Desbrochers des Loges, 1896)), Chiloneus ottomanus Desbrochers des Loges, 1892, Chiloneus veneriatus Normand, 1937, Eusomus sphaeropterus Allard, 1869 (currently Chiloneus pertusicollis (Fairmaire, 1868)), Foucartia ruficornis Allard, 1869 (currently Chiloneus pertusicollis (Fairmaire, 1868)), Holcorhinus parvus Stierlin, 1899 (currently Chiloneus chevrolati Tournier, 1874), Platytarsus vaulogeri Desbrochers des Loges, 1897 (currently Chiloneus barbaricus (Gonzalez, 1970)), Sciaphilus alboscutellaris Pic, 1917 (currently Chiloneus submaculatus (Pic, 1917)), Sciaphilus alluaudi Pic, 1903 (currently Chiloneus vaulogeri (Pic, 1896)), Sciaphilus chobauti Desbrochers des Loges, 1897 (currently Chiloneus chobauti (Desbrochers des Loges, 1897)), Sciaphilus convexiceps Desbrochers des Loges, 1896 (currently Myochlamys convexiceps (Desbrochers des Loges, 1896)), Sciaphilus curtipennis Pic, 1917 (currently Desbrochersella diversepubens (Pic, 1904)), Sciaphilus diversepubens Pic, 1904 (currently Desbrochersella diversepubens (Pic, 1904)), Sciaphilus dividuus Pic, 1904 (currently Chiloneus pennatus (Faust, 1885)), Sciaphilus inhumeralis Pic, 1903 (currently Chiloneus chobauti (Desbrochers des Loges, 1897)), Sciaphilus innotatus Pic, 1927 (currently Chiloneus innotatus (Pic, 1927)), Sciaphilus microps Desbrochers des Loges, 1897 (currently Desbrochersella microps (Desbrochers des Loges, 1897)), Sciaphilus minutissimus Pic, 1904 (currently Chiloneus minutissimus (Pic, 1904)), Sciaphilus nasutus Desbrochers des Loges, 1897 (currently Chiloneus pertusicollis (Fairmaire, 1868)), Sciaphilus nitens Pic, 1904 (currently Chiloneus cinerascens (Rosenhauer, 1856)), Sciaphilus pertusicollis Fairmaire, 1868 (currently Chiloneus pertusicollis (Fairmaire, 1868)), Sciaphilus pruinosus Desbrochers des Loges, 1896 (currently Chiloneus pennatus (Faust, 1885)), Sciaphilus subannulipes Pic, 1917 (currently Chiloneus minutissimus (Pic, 1904)), Sciaphilus submaculatus Pic, 1917 (currently Chiloneus submaculatus (Pic, 1917)), Sciaphilus vaulogeri Pic, 1896 (currently Chiloneus vaulogeri (Pic, 1896)). PMID- 27394858 TI - Six, not two, species of Acisoma pintail dragonfly (Odonata: Libellulidae). AB - The dragonfly genus Acisoma is revised based on adult male morphology and COI sequence data. Six species are recognised, including the new species A. attenboroughi sp. nov. Diagnoses and a key to males of all species and illustrations of all relevant characters are provided. A. inflatum, A. variegatum and A. trifidum are confined to continental Africa, while A. panorpoides is restricted to Asia. A. ascalaphoides is known only from threatened littoral forest fragments on the east coast of Madagascar, while A. attenboroughi is widespread across the island. The new species honours Sir David Attenborough on his 90th birthday. PMID- 27394859 TI - Five new species of the family Trischistomatidae (Nematoda: Enoplida) from North and Central America, with keys to the species of Trischistoma and Tripylina. AB - Three new species of Trischistoma and two new species of Tripylina (Trischistomatidae) are described. Trischistoma ripariana n. sp. was collected in the surface organic material and upper rhizosphere soil on a stream bank in Oakville, California, USA. It is characterized by a short, thin body, the vulva at 79-83%, a small index c (17-29) and a short tail, 34-57 um. Trischistoma corticulensis n. sp. was found in moss on tree bark in a tropical forest at the La Mancha Ecological Institute, Veracruz State, Mexico. The vulva is at 67-73% and the tail is elongate conoid (51-84 um). Trischistoma helicoformis n. sp. was collected on lichen growing on tree bark near the Carretera Interamericana in Costa Rica. It is characterized by its spiral shape after fixation, the tail length (76-101 um), a very small index c (10-14.5) and very small sclerotised pieces around the vagina. Tripylina rorkabanarum n. sp. was collected from moss on tree bark in a tropical forest at the La Mancha Ecological Institute. It is characterized by the presence of two cervical setae, the position of the subventral teeth posterior to the dorsal tooth, the absence of sclerotized pieces around the vagina and the distance of the dorsal tooth from the anterior, 10-15 MUm. Tripylina iandrassyi n. sp. was collected from soil around a banana tree at the La Mancha Ecological Institute. It is characterized by the presence of a post uterine sac, well-developed buccal lips, subventral teeth located posterior to the dorsal tooth, one cervical seta in females and two in males, and by spicules not completely surrounded by a muscular sheath. PMID- 27394860 TI - Five new species of the genus Tripylella (Nematoda: Enoplida: Tripylidae). AB - Five new species of the genus Tripylella are described, two from Mexico, one from Fatima, Portugal, one from Quito, Ecuador, and one from California, USA. Tripylella mexicana sp. n. is characterized by its short body (average 0.74 mm), short pharynx (average 161 MUm), short tail (average 117 MUm), presence of an excretory pore and small setae distributed sparsely along the body, the presence of body pores, the posterior position of the subventral teeth in relation to the small dorsal tooth with all teeth in contiguous stomal chambers, the finely striated cuticle with many anastomoses, the non-protruding vulval lips, and the presence of sclerotized pieces in the vulval region. Tripylella muscusi sp. n. is characterized by its body length (average 0.94 mm), pharynx length (average 201 MUm), tail length (average 140 MUm), the anterior position of the subventral teeth in relation to the small dorsal tooth in a single stomal chamber, the presence of an excretory pore, the presence of body pores and sparse somatic setae, the finely-striated cuticle with sparse anastomoses, protruding vulval lips and sclerotized oval-shaped pieces present in the vulval region. Tripylella quitoensis sp. n. is characterized by the short body length (average 0.72 mm), the short outer labial setae, the short pharynx (average 175 MUm), the location of the anterior subventral teeth and posterior dorsal tooth in the same stomal chamber, the short tail (average 98 MUm), the apparent absence of an excretory pore, presence of body pores, presence of somatic setae, a finely-striated cuticle, non-protruding vulval lips, and very small oval sclerotized pieces in the vulva. Tripylella fatimaensis sp. n. is characterized by the short body, (average 0.74 mm) long, by the length of the pharynx (average 180 MUm), the length of the tail (average 110 MUm) and in the length of its reduced diameter portion, 45-58 MUm, the presence of an excretory pore, body pores and three pairs of caudal setae (one pair each latero-ventral, latero-dorsal and ventral). Tripylella dentata sp. n. is characterized, and differs from all the species of the genus, by the presence of two adjacent stomal chambers, with two large teeth, one dorsal and one ventral, in the posterior stomal chamber and two subventral teeth in the anterior smaller chamber, short body (average 0.85 mm), pharynx length (average 209 MUm), tail length (average 115 MUm), the apparent absence of an excretory pore, the presence of two cervical setae in a lateral position, and by the presence of conspicuous pores along the body. PMID- 27394861 TI - Amblyceps accari, a new species of torrent catfish (Teleostei: Amblycipitidae) from the Western Ghats of India. AB - A new species of torrent catfish, Amblyceps accari, is described from the central region of the Western Ghats of India. The new species differs from all its congeners by having 12 branched anal-fin rays (vs. 7-10 in other Amblyceps, rarely 11 in A. tuberculatum). It differs further from all other species of the genus except A. murraystuarti and A. torrentis in having the adipose fin confluent with the dorsal procurrent part of the caudal fin and by the following combination of characters from all its congeners: jaws unequal with lower jaw weakly-projecting, pectoral spine smooth, adipose-fin origin opposite anal-fin origin, dorsal fin to adipose-fin distance more than one fourth of standard length, adipose fin long with its base more than one-fourth of standard length, and deeply forked caudal fin with minute, poorly developed, centrally projecting hooks on the proximal lepidotrichia of central caudal-fin rays. The discovery of the new species represents the first record of this genus from peninsular India. PMID- 27394862 TI - A new species of Hisonotus (Siluriformes: Otothyrinae) from the upper rio Parana and rio Sao Francisco basins, Brazil. AB - A new species of Hisonotus is described from the upper rio Parana and rio Sao Francisco basins. The new species is distinguished from congeners by (1) completely exposed abdomen with no development of dermal plates (with the exception of extremely small platelets present near the urogenital pore in some specimens) and the combination of the following characters: (2) lack of a conspicuous tuft of enlarged odontodes on posterior tip of parieto supraoccipital; (3) rectangular dorsal-fin spinelet; (4) complete mid-lateral plate series; (5) higher number of vertebrae, 29-30; (6) dark brown coloration on caudal fin with one pair of circular hyaline colored regions at center of both lobes; (7) absence of broad light stripes on dorsolateral surface of head; (8) odontodes not forming longitudinally aligned rows on head and trunk; and (9) apex of teeth yellowish in color. PMID- 27394863 TI - New Rhinotragini (Coleoptera, Cerambycidae) from Central and South America. AB - Two new species of Rhinotragini are described: Chrysaethe panamensis, from Panama, and Rashelapso morrisoni, from Ecuador. Key to species of Rashelapso is provided. PMID- 27394864 TI - A NEW SPECIES OF Bolivar Zaldivar-Riveron et Rodriguez-Jimenez (BRACONIDAE, DORYCTINAE) FROM BRAZIL, WITH NEW RECORDS OF THE AMAZONIAN B. ecuadorensis Zaldivar-Riveron et Lopez-Estrada. AB - A new species of the doryctine genus Bolivar (Braconidae), B. brasiliensis sp. nov., is described from the Atlantic coastal region in Brazil. New records and taxonomic notes of the Amazonian B. ecuadorensis Zaldivar-Riveron et Lopez Estrada are also provided. PMID- 27394865 TI - Twelve new species of Triplocania Roesler (Psocodea: 'Psocoptera': Ptiloneuridae), from South America. AB - Twelve species of Triplocania, seven based on male and female specimens and five based on male specimens, are here described and illustrated; nine species are Brazilian, three are Ecuadorian, and one of the latter is shared with Peru. Comments on sexes known and distribution of the species are included. PMID- 27394866 TI - A review of the genus Trachylepis (Sauria: Scincidae) from the Gulf of Guinea, with descriptions of two new species in the Trachylepis maculilabris (Gray, 1845) species complex. AB - The scincid genus Trachylepis is represented in the oceanic islands of the Gulf of Guinea by four species, Trachylepis maculilabris, T. affinis, T. adamastor and T. ozorii. Here we describe two new species, Trachylepis thomensis sp. nov., endemic to Sao Tome Island and Rolas Islet, and Trachylepis principensis sp. nov., endemic to Principe Island. Phylogenetic analysis using the mitochondrial gene 16S shows that both new species are genetically divergent and reciprocally monophyletic, and confirms evidence for the uniqueness of these lineages presented in previous studies. Morphological data (scalation and morphometry) identify consistent phenotypic differences between these two island species. We were also able to confirm that the T. affinis population of Principe Island is conspecific with the African mainland population and most probably the result of recent introductions. These findings raise the number of known Trachylepis species in the Gulf of Guinea islands group to five, four of which are endemic, although the phylogenetic and phylogeographic relationships of T. adamastor and T. ozorii remain unknown and require further investigation. PMID- 27394867 TI - Conochironomus (Diptera: Chironomidae) in Asia: new and redescribed species and vouchering issues. AB - The presence of the Afro-Australian genus Conochironomus Freeman, 1961 (Diptera: Chironomidae) in Asia has been recognised only informally. An unpublished thesis included Conochironomus from Singapore, and the genus has been keyed from Malaysia without named species. Here, the Sumatran Conochironomus tobaterdecimus (Kikuchi & Sasa, 1980) comb. n. is recorded from Singapore and Thailand. The species is transferred from Sumatendipes Kikuchi & Sasa, 1980, rendering the latter a junior synonym (syn. n.) of Conochironomus Freeman. Conochironomus nuengthai sp. n. and Conochironomus sawngthai sp. n. are described as new to science, based on adult males from Chiang Mai, Thailand. All species conform to existing generic diagnoses for all life stages, with features from male and female genitalia, pupal cephalic tubercles and posterolateral 'spurs' of tergite VIII providing evidence for species distinction. Some larvae are linked to C. tobaterdecimus through molecular barcoding. Variation in other larvae, which clearly belong to Conochironomus and are common throughout Thailand, means that they cannot be segregated to species. Larval habitats include pools in river beds, urban storage reservoirs, drains with moderately high nutrient loadings, and peat swamps. Endochironomus effusus Dutta, 1994 from north-eastern India may be a congener but may differ in adult morphology, thereby precluding formal new combination until discrepancies can be reconciled. Many problems with vouchering taxonomic and molecular material are identified that need to be rectified in the future. PMID- 27394868 TI - Three new Asiatic species of Hyadaphis (Hemiptera, Aphididae). AB - Three new species of Hyadaphis Kirkaldy, 1904 (Hemiptera, Aphididae, Macrosiphini) are established: Hyadaphis levantina sp. n. from specimens caught on Lonicera nummulariifolia from Lebanon and Israel, and Hyadaphis anethi sp. n. plus Hyadaphis parva sp. n. from specimens respectively caught on Anethum sp. and Andrachne (?) cordifolia from Pakistan. Apterous viviparous females of all three species, alate viviparae of the first two and males of H. anethi are described. Known and new species of Hyadaphis are grouped for two relevant characters: (1) size and shape of siphunculi, and (2) host plant and life cycle; and the discriminant features of apterous viviparous females of the new species are compared with the already described species of the same group and a key for the Hyadaphis species is provided. PMID- 27394869 TI - A new extinct species of Snipe (Aves: Scolopacidae: Gallinago) from the West Indies. AB - We describe an extinct species of snipe (Gallinago kakuki, new species) from late Quaternary fossils in the Bahamian Archipelago (Abaco, New Providence, Little Exuma, Long, and Middle Caicos islands). The new species is known as well from fossils on Cuba, and Cayman Brac in the Cayman Islands. This rather large species of snipe was volant, although because of its relatively short carpometacarpus, the primary flight feathers probably were short. The only other species of Gallinago from the West Indies is the extant, migratory G. delicata, which breeds only in North America. Gallinago kakuki shares more osteological characters with two Eurasian species (G. media, G. hardwickii) than with either of the New World species we examined (G. delicata, G. paraguaiae). A possible inter-hemispherical relationship has been proposed as well for the two extinct, late Quaternary species of woodcocks from the West Indies (Scolopax anthonyi of Puerto Rico, S. brachycarpa of Hispaniola). PMID- 27394870 TI - Three new species of the subfamily Opisthocosmiinae from China (Dermaptera, Forficulidae), with new synonymies and combinations. AB - This article contains descriptions of three new species of Chinese Dermaptera: Timomenus bicolor sp. nov. from Xizang, Timomenus bii sp. nov. from Yunnan and Cordax serratus sp. nov. from Guangxi. Four new specific synonymies and three new combinations are proposed. We also emend the generic diagnosis of Mesolabia Shiraki, 1906 by providing characteristics of the male. Keys to the species of Timomenus, Cordax and Mesolabia from China are provided. PMID- 27394871 TI - The Lepidoptera of White Sands National Monument, Otero County, New Mexico, USA 10. A remarkable new white species of Chionodes Hubner (Gelechiidae). AB - The U.S. National Park Service initiated a 10-year study, in late 2006, of the Lepidoptera at White Sands National Monument, Otero County, New Mexico. Chionodes bustosorum sp. n., described here, was discovered in 2010, during the third year of the study. The male imago and male genitalia are illustrated, and its DNA barcode is compared to that of seven other species of Chionodes from western North America. PMID- 27394872 TI - Can the name Mugil cephalus (Pisces: Mugilidae) be used for the species occurring in the north western Atlantic? AB - Menezes et al. (2010) show that Mugil cephalus Linnaeus, 1758 is different from Mugil liza Valenciennes 1836, the latter being the mullet found along the Atlantic coast of South America. They also suggest that individuals identified as M. cephalus from the northwest Atlantic could represent a population of M. liza in this region, since they doubt the presence of M. cephalus in waters colder than the ones of the West Indies. In order to clarify the presence of M. cephalus in the northwest Atlantic, this study compares meristic and morphometric measurements of M. cephalus and M. liza from the Gulf of Mexico with those obtained by Menezes et al. (2010) for M. liza from South America and for M. cephalus in the Mediterranean Sea. Results show that there are differences in both morphometric and meristic data between the two species. The morphometric measure that differentiates these species is the distance from the snout to the dorsal fin, which is positioned backwards in M. liza compared with M. cephalus. The body width is consistently greater in M. cephalus than M. liza. The meristic character that discriminates between both species is the number of scales in the longitudinal series that, in M. cephalus, ranges from 38 to 43 while in M. liza between 32 to 39. The information presented in this work confirms the presence of M. cephalus in the Gulf of Mexico and the sympatric presence of M. liza is established, even if its abundance is quite low. PMID- 27394873 TI - An overlooked sibling of the fruit-piercing moth Eudocima phalonia (Linnaeus, 1763) from Africa (Lepidoptera, Erebidae, Calpinae). AB - In recent years, we have been investigating the tropical calpine genus Eudocima Billberg, 1920 (Lepidoptera, Erebidae, Calpinae) with the intent of producing a generic revision. There are a number of undescribed species and here we describe as new a closely related species to the widespread and economically important fruit-piercer Eudocima phalonia (Linnaeus, 1763) (= fullonia Clerck, 1764), with which it has long been confused. Study material came from the private collection of Vernon Antoine Brou collection (VAB) and the Natural History Museum, London (NHM). PMID- 27394874 TI - TIAGO F. CARRIJO, RUDOLF H. SCHEFFRAHN & JAN KRECEK (2015) Compositermes bani sp.n. (Isoptera, Termitidae, Apicotermitinae), a new species of soldierless termite from Bolivia. Zootaxa, 3941(2): 294-298. PMID- 27394875 TI - Free living marine nematodes of the genus Parodontophora (Axonolaimidae) from the East China Sea, with descriptions of five new species and a pictorial key. AB - Five new species of free living marine nematodes belonging to genus Parodontophora are described from intertidal areas of Fujian Province, East China Sea. P. aequiramus sp. nov. is identified by the amphid with the same length of dorsal branch and ventral branch, opisthocephalic setae arranged as (2D-1V)2, precloacal supplements and armilliths present; Parodontophora irregularis sp. nov. is characterized by arranged irregularly opisthocephalic setae, excretory pore near cephalic setae at the anterior part of buccal cavity and precloacal supplements present; Parodontophora huoshanensis sp. nov. can be distinguished by the amphid 0.77-0.83 times the length of the buccal cavity, opisthocephalic setae arranged as (2D-1V)2 and precloacal supplements present; Parodontophora microseta sp. nov. is characterized by the amphid 1.71-2.1 times the length of the buccal cavity, opisthocephalic setae arranged as (1D-1V)2, precloacal supplements present and anterior gonad to the right and posterior gonad to the left of the intestine; Parodontophora paramicroseta sp. nov. is characterized by the amphid 1.35-1.5 times the length of the buccal cavity, opisthocephalic setae arranged as (1D-1V)2, precloacal supplements present and anterior gonad to the left and posterior gonad to the right of the intestine. A pictorial key to the valid species of Parodontophora Timm, 1963 is given. PMID- 27394876 TI - A new genus and species of gekkonid lizard (Squamata: Gekkota: Gekkonidae) from Hormozgan Province with a revised key to gekkonid genera of Iran. AB - We describe a new genus and species of gekkonid from two gravid specimens which were found within Koh-e Homag Protected Area, Hormozgan Province, southern Iran. The genus Parsigecko gen. nov. can be distinguished from other genera of Middle East Gekkonidae by a combination of the following characteristics: digits not dilated, dorsal tail covered with small scales without any tubercles or keels, having two strong keeled and pointed scales on each side of each annulus. Parsigecko ziaiei sp. nov. is a ground-dwelling lizard. The new species was found in the Zagros Mountain forest steppe patch with scattered wild pistachio trees and mountain almond shrubs surrounded by South Iran Nubo-Sindian desert and semi desert habitat in the south of Iran. The genus is the 13th gekkonid genus known from Iran, and the only gekkonid genus endemic to the Zagros Mountains. A key to the genera of the Gekkonidae in Iran is provided. PMID- 27394877 TI - Haplopacha (Lepidoptera: Lasiocampidae) reviewed: four new species, first descriptions of the genitalia of both sexes, and unique alar scale organs. AB - The collection of five specimens of Haplopacha at Ndumo Nature Reserve in South Africa highlights unknown species diversity in the monotypic genus. A total of four new species; H. riftensis sp. nov., H. tangani sp. nov., H. lunata sp. nov. and H. ndoumoi sp. nov., were identified in the Natural History Museum of London collection and the study of fresh specimens also revealed the presence of uniquely characteristic alar scale patches absent from the original species description of the genus type species H. cinerea. Based on the new species the descriptions of Haplopacha is amended. The identification of the new species was done using conventional light microscopy and scanning electron microscopy of the general morphology, wing venation and genitalia observations. PMID- 27394878 TI - Southwestern Atlantic species of conoidean gastropods of the genus Aforia Dall, 1889. AB - A new species of the conoidean genus Aforia is described from the Southwestern Atlantic in Argentine deep waters. Detailed study of the type material of nominal species, Aforia goniodes (Watson, 1881) and its synonym Pleurotoma clara Martens, 1880, both described from deep waters off Argentina, allowed recognition of a new species. Aforia obesa sp. nov. was collected from 7 stations in 647 to 1,398 m depth during three cruises to the Mar del Plata submarine Canyon in the Argentine continental slope on the R/V "Puerto Deseado". Shells, radulae, penises and opercula of adults and juveniles of A. obesa n. sp. from several localities are illustrated, described and compared to other living congeners. PMID- 27394879 TI - A new Theosbaena (Thermosbaenacea: Halosbaenidae) from Thailand. AB - We present a second species of Theosbaena, which also represents the second species of Thermosbaenacea from mainland Asia. This new species is apparently endemic to a limestone cave in Nakhon Sawan Province in central Thailand. Theosbaena kiatwongchai n. sp. is separated from T. cambodjiana by the form of the gnathopod, the form of the pereopod exopodites, the lack of a pleopod I, and a cleft telson. PMID- 27394880 TI - Two new Meitingsunes species (Acari: Syringophilidae) from Indonesian doves (Columbiformes: Columbidae). AB - We describe two new quill mite species of the genus Meitingsunes Glowska and Skoracki, 2010 (Acari: Prostigmata: Syringophilidae) parasitizing columbiform birds (Columbiformes: Columbidae): M. chalcophaps sp. nov. collected from the Emerald Dove, Chalcophaps indica (Linnaeus) and M. turacoenas sp. nov. from the White-faced Cuckoo Dove, Turacoena manadensis (Quoy and Gaimard) (type host) and the Black Cuckoo-Dove, Turacoena modesta (Temminck). All host species were collected in Indonesia. These represent two new genus-level host records for Meitingsunes. In addition, we summarize the diversity of Meitingsunes and present a key to species in this genus. PMID- 27394881 TI - A new species of Campylothorax Schott, 1893 (Collembola, Paronellidae) from Brazilian Amazon, with an identification key to the genus. AB - A new species of Campylothorax from Brazilian Amazon is described and illustrated. Campylothorax plagatus sp. nov. resembles another Neotropical species, C. cubanus, by abdomen with two transverse bands and pattern of dorsal chaetotaxy. However, the new species differs by unguis with one unpaired apical tooth, unguiculi III truncate, and abdomen IV with 5+5 posterior central macrochaetae. This is the first species of Campylothorax originally described from Brazilian Amazon. A generic key to the 14 species of Campylothorax is provided. PMID- 27394882 TI - Description of a new genus, Galgoria gen. nov. (Hemiptera: Cicadidae: Cicadinae: Leptopsaltriini: Leptopsaltriina). AB - A new cicada genus, Galgoria gen. nov., is described with Tanna herzbergi Schmidt, 1932 (from southern China) as its type species, which is placed in the subtribe Leptopsaltriina Moulton, 1923 of the tribe Leptopsaltriini Moulton, 1923 in the subfamily Cicadinae Latreille, 1802 (Hemiptera: Cicadidae). Tanna herzbergi Schmidt, 1932 is transferred from Tanna Distant, 1905 to Galgoria gen. nov. to become Galgoria herzbergi (Schmidt, 1932) comb. nov. Tanna apicalis Chen, 1940 syn. nov. and Tanna pseudocalis Lei & Chou, 1997 syn. nov. are synonymized here with Galgoria herzbergi (Schmidt, 1932) comb. nov. PMID- 27394883 TI - A taxonomic revision of the Neotropical termite genus Rhynchotermes (Isoptera, Termitidae, Syntermitinae). AB - We herein revise the taxonomy of the Neotropical syntermitine genus Rhynchotermes Holmgren. Seven species were recognized and diagnosis given for all available castes. This includes two new species: Rhynchotermes amazonensis Constantini & Cancello sp. nov. and Rhynchotermes matraga Constantini & Cancello sp. nov. Rhynchotermes guarany Cancello is recognized as syn. nov. of Rhynchotermes nasutissimus (Silvestri) and Rhynchotermes nyctobius Mathews syn. nov. of Rhynchotermes diphyes Mathews. The three other formerly described species include Rhynchotermes perarmatus (Snyder), Rhynchotermes piauy Cancello and Rhynchotermes bulbinasus Scheffrahn. We also provide a key to the soldiers of the genus, a distribution map of the species as well as illustrations and biological notes for all species. PMID- 27394884 TI - A new species of Blaesodactylus (Squamata: Gekkonidae) from Tsingy limestone outcrops in Namoroka National Park, north-western Madagascar. AB - We describe a new gekkonid lizard of the genus Blaesodactylus from Tsingy limestone of a deciduous dry forest of Namoroka National Park, north-western Madagascar. Blaesodactylus victori sp. nov., the sixth recognized species of this genus, is distinguished from all other congeners by its large size and a combination of regular small gular granules, spotted venter, lack of dorsal tubercles, enlarged supranasal scales separated ventrally by a much smaller scale in contact with the rostral, and black naris. The new arboreal species is also characterized by its dark dorso-ventral stripes on the head separating infralabial and most supralabial plates and in life by a typical white spotted pattern on a washed grey to dark grey vermiculated dorsum. Molecular phylogenetic data place the species into a clade with B. boivini and B. microtuberculatus, as sister to a subclade containing these two species. The new species shares some morphological characters states with its African sister genus Homopholis, suggesting that its morphology might be rather plesiomorphic. We also identify several previously overlooked morphological traits characterizing the entire B. boivini clade, possibly also being plesiomorphic. Due to its extremely limited presumed extent of occurrence and continuing decline of its habitat we propose an IUCN Red List status of "Critically Endangered" for the new species. PMID- 27394885 TI - New records of the squat lobster genus Munida Leach, 1820 (Crustacea: Decapoda: Anomura: Munididae) from deep-water off Okinawa Islands, Ryukyu Islands, Japan, with description of a new species. AB - Two species of the squat lobster genus Munida Leach, 1820, M. pollioculus n. sp. and M. zebra Macpherson, 1994, are recorded from deep-waters off Okinawa Islands, the Ryukyu Islands, at depths of 1000 m and 495 m, respectively. The new species closely resembles M. clevai Macpherson, 1999 and M. microps Alcock, 1894, but it differs from the latter two in the absence of a proximal spine on the mesial margin of the cheliped dactylus and the more stout dactylus of the second pereopod. Munida zebra is first recorded from the Northwest Pacific, as well as Japanese waters, with its geographical range extended to the north from the previously known southwestern Pacific localities. PMID- 27394886 TI - Checklist of the Cerambycidae (Insecta, Coleoptera) from central Bahia State (Brazil), with the description of two new species and new geographic records. AB - A list of Cerambycidae species from three municipalities of central Bahia (Milagres, Maracas and Iacu) is presented. A total of 108 species are registered, 17 of which are new geographical records for the state, are listed, including two new species of Aerenicini (Lamiinae), Suipinima flavumtuberculata sp. nov. and Aereniphaula bandana sp. nov. which are described and illustrated. A key to the species of Suipinima and taxonomic notes on Suipinima eccentrica (Galileo & Martins, 1992) are provided. PMID- 27394887 TI - Genera of the leaf-feeding Dendrothripinae of the world (Thysanoptera, Thripidae), with new species from Australia and Sulawesi, Indonesia. AB - Character states used in distinguishing taxa within the Thripidae subfamily Dendrothripinae are discussed, and a key presented to the 11 genera recognized worldwide. Comments on each of these genera are provided, together with keys to the species from Australia of Dendrothrips, Ensiferothrips and Pseudodendrothrips. From Australia are described, four new species of Dendrothrips, one of Pseudodendrothrips, and a remarkable new species of Ensiferothrips that has required a re-diagnosis of that genus. Another new species of Ensiferothrips is described from Sulawesi, thus greatly extending the known geographical range of this previously Australian genus. PMID- 27394889 TI - Description of Eutetrapha weni n. sp. from Guizhou, China (Coleoptera: Cerambycidae: Lamiinae: Saperdini). AB - Eutetrapha weni n. sp. is described from Leigongshan, Guizhou, China. PMID- 27394888 TI - Rubiparvus bistigma, a new genus and species of Empoascini (Hemiptera, Cicadellidae, Typhlocybinae), with a checklist of the Alebroides group in Chinese fauna. AB - A new leafhopper genus of the tribe Empoascini, Rubiparvus gen. nov., is described based on Rubiparvus bistigma sp. nov. from Yunnan (southwest China). Habitus photos and illustrations of male genitalia of this new species are given. Differences between the new genus and closely related genera are discussed. A checklist of the Alebroides generic group in the Chinese fauna is provided. PMID- 27394890 TI - First fossil record of Ischaliidae Blair, 1920 (Coleoptera) from Eocene Baltic amber. AB - Ischalia Pascoe, 1860, the monotypic genus of Ischaliidae, was placed as a subfamily among Pyrochroidae or Anthicidae by earlier authors. Nikitsky (1992) raised the status of Ischaliidae to the family rank. This position has been largely accepted and consequently followed by recent authors dealing with Ischalia, as well as in our paper. Ischaliidae is known from the Palaearctic (the Himalayas, East Asia: easternmost Russia, Japan, E China), South East Asia (southwards to Java, Borneo and the Philippines), and the Nearctic region (southern Canada, U.S.A.). No recent European representatives of Ischalia are known. At present, this genus is composed of 43 species worldwide (Gusakov & Telnov 2007; Saito 2011; Young 2011; Young 2014; Saito & Young 2015) placed in three subgenera (Young 2011): Ischalia s. str.-37 species, Eupleurida LeConte, 1862-5 species, Nitidischalia Young, 2011-1 species. Ischaliidae is most diverse in tropical rainforests, but many species are also known from subtropical to temperate zones. Adults and larvae of two Nearctic Ischalia feed on fungal mycelium growing on decaying wood of coniferous and broad-leaved trees (e.g. Pinus ponderosa, Lithocarpus densiflora) (Young 1985). Mimicry has been described among Bornean Ischaliidae, Tenebrionidae and Chrysomelidae (Telnov 2005) and also among Ischaliidae, Omalisidae, Lycidae and Endomychidae (Kazantsev & Young 2010). PMID- 27394891 TI - ALEXEY RESHCHIKOV & ILARI EERIKKI SAAKSJARVI (2015) Seven new species of the genus Physotarsus Townes 1966 (Hymenoptera, Ichneumonidae) from South America. Zootaxa, 3972(1): 026-042. PMID- 27394892 TI - Checklist of Cerambycidae (Coleoptera) primary types of the Museu Nacional, Rio de Janeiro, Brazil, with a brief history of the collection. AB - A checklist of the Cerambycidae (Coleoptera) primary types deposited in the Museu Nacional, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil is given. There are 1,044 primary types. Lectotype designation for Megacyllene castroi (Prosen, 1947) is proposed. A brief history of the collection of Cerambycidae of the Museu Nacional is presented. PMID- 27394893 TI - Resurrection of Scolopendra longipes Wood and Scolopendra cubensis Saussure from synonymy with Scolopendra alternans Leach (Chilopoda, Scolopendromorpha, Scolopendridae): an enigmatic species-group needing phylogeographic analysis, with an overview on the origin and distribution of centipedes in the Caribbean region. AB - Resurrection of Scolopendra longipes Wood, 1862, and Scolopendra cubensis Saussure, 1860, from junior synonymy with Scolopendra alternans Leach, 1815, is proposed. A neotype specimen of Scolopendra longipes is designated. Scolopendra longipes has a restricted range from the Dry Tortugas up through the Florida Keys of Monroe County into the mainland Florida counties of Collier and Dade southeast to the Bahamas, while Scolopendra cubensis is endemic to Cuba. Characters distinguishing S. longipes, and S. cubensis from S. alternans are illustrated and compared using digital photography, micrography and morphometric data. It is suggested that what has been considered Scolopendra alternans from southern Florida through the Caribbean and into northern South America is probably an evolving species-group that has undergone major diversification sometime during the Paleocene and early Eocene ~65.5-50 million years ago (Ma), mainly due to geographic isolation caused by a combination of plate tectonics and 100,000 year cycles of glaciation/deglaciation. PMID- 27394894 TI - A contribution to the knowledge of Orthoptera diversity from Peninsular Malaysia: Bukit Larut, Perak. AB - Bukit Larut is a hill station at the southern tip of the Bintang Range, Perak of Peninsular Malaysia. While the biodiversity of Bukit Larut has been previously documented, its entomofauna, including the Orthoptera, remains relatively unknown. A faunistic survey was conducted in 2015 as part of the continuous exploration of the highlands in Malay Peninsula. An annotated species list of 71 (24 Caelifera and 47 Ensifera) species of Orthoptera from ten families (five from each order) is presented here. While the coverage of lineages in the orthopteran phylogeny is well-represented, the diversity in Bukit Larut is dominated by the three main families: Acrididae, Gryllidae and Tettigoniidae. Eight new locality records for Bukit Larut and/or Peninsular Malaysia and potential new species awaiting description highlight that the orthopteran diversity in Bukit Larut is not exhaustive. PMID- 27394895 TI - Redescription of Alox chaunos Galil & Ng, 2007 (Crustacea: Decapoda: Brachyura: Leucosiidae) new to Japan; with notes on the male characters of A. latusoides (Sakai, 1937). AB - The leucosiid crab Alox chaunos Galil & Ng, 2007 is reported from Japan for the first time, and redescribed on the basis of specimens from the Ryukyu Islands. The taxonomy of this species is discussed, and comparisons are made with A. rugosum (Stimpson, 1858), A. uru Naruse & Ng, 2006, and A. liklik Galil & Ng, 2015. Alox somphos Tan & Ng, 1995, is excluded from the fauna of Japan, the original record actually based on a specimen of A. chaunos. Male characters of A. latusoides are also described for the first time to differentiate this species from A. chaunos. PMID- 27394896 TI - Review of the genus Rhaphiocerina Lindner (Diptera: Stratiomyinae), with description of a new species. AB - Genus Rhaphiocerina is revised and discussed. The known species R. hakiensis (Matsumura, 1916) is redescribed and illustrated. A new species, Rhaphiocerina chinensis sp. nov., is described and illustrated. A key is presented to separate the known genera in Stratiomyinae from China. PMID- 27394897 TI - Metopina Macquart (Diptera: Phoridae) of Israel, with description of a new species, new records and an identification key. AB - Metopina kuslitzkyi sp. n. with a rudimentary anterior flap on tergite 5 in female is described from Israel. Four other species, the Palaearctic Metopina braueri, M. pileata, M. ulrichi and Afrotropical M. obsoleta, have been recorded from Israel for the first time, in addition to the previously known M. heselhausi. An illustrated identification key to the Israeli species of Metopina is provided. PMID- 27394898 TI - The Taiwanese species of the genus Paraphloeostiba Steel, 1960 (Coleoptera: Staphylinidae: Omaliinae: Omaliini). AB - Paraphloeostiba formosana sp. n. from Taiwan is described. Paraphloeostiba sonani (Bernhauer, 1943) is redescribed, the lectotype of Phloeonomus sonani Bernhauer, 1943 is designated. Both species are illustrated. A key to the species of Paraphloeostiba Steel, 1960 of Taiwan is given. PMID- 27394899 TI - Vatellini Sharp (Coleoptera, Dytiscidae) from Brazil: two new species, new records, and a checklist. AB - The tribe Vatellini Sharp, 1882 is composed of 55 species divided in two genera. Even though a recent revision of the tribe was made, Vatellini of the new world are weakly explored with great gaps in the distributions of species. In Brazil the knowledge is based only on a few localities. In this work two new species are described and illustrated, Vatellus caissara sp. nov. and Vatellus yanomami sp. nov.; new records are given for Brazil: Vatellus maculosus Miller, 2005 in the state of Mato Grosso, Derovatellus lentus (Wehncke, 1876) in Amazonas, Para and Rio de Janeiro, Vatellus lateralis (Sharp, 1882) in Alagoas, Ceara, Espirito Santo, Para, Pernambuco and Rio Grande do Sul, Vatellus sahlbergi (Sharp, 1882) in Rio de Janeiro, and Vatellus tarsatus (Laporte, 1835) in Para. A checklist with all species of Vatellini occurring in Brazil is provided and steps for identification of the new species are added in the key of Miller (2005). PMID- 27394900 TI - Nemachilichthys ruppelli (Teleostei: Nemacheilidae) and the proper correction of the German umlaut. AB - In a re-description of the South Asian fish species Nemachilichthys ruppelli (Sykes, 1839a) Keskar et al. (2015) noticed-as also pointed out by Kottelat (2012)-that the original spelling of the species name was rupelli [actually: Rupelli, with regular font and capital R], but that information in Sykes (1839a: 162) showed clearly that the species was named for [Eduard] Ruppell with the explicit dedication "I have dedicated this beautiful little fish to Ruppell, who did me the favor to look over my drawings ..." Ruppell is also mentioned twice on page 159. Sykes's (1839a) paper was reprinted in Sykes (1839b) with exactly the same spelling, but there the species name appears in italics. A third publication by Sykes (1841), based on the same material, also uses the spelling Rupelli for the species, but does not mention Ruppell. PMID- 27394901 TI - Corrigendum: Redescription of Nemachilichthys rueppelli, a senior synonym of N. shimogensis (Teleostei: Nemacheilidae). AB - In Keskar et al. (2015) we emended the original name Cobitis rupelli Sykes, 1839, because Sykes (1839) specifically mentions that the species was named after Ruppell. The specific epithet 'rupelli', with a single 'p', is an incorrect original spelling and should be emended into 'ruppelli' as required by Article 32.5 (International Commission on Zoological Nomenclature, 1999). However, citing Art 32.5.2.1, we also suggested that because Sykes (1839) named the species after Ruppell, the umlaut 'u' should be corrected to 'ue' and that the specific epithet should thus be 'rueppelli'. This is an error. Sykes (1839) did not use 'u' in the original spelling of the species epithet rupelli: hence changing it to 'ue' is incorrect. Therefore, the correct spelling for the species should be 'Nemachilichthys ruppelli', a change that should be reflected in the title and in the rest of the text of Keskar et al. (2015). PMID- 27394902 TI - Mud-shrimps of the genus Axianassa Schmitt, 1924 from Panama, with description of two new species (Decapoda: Gebiidea: Laomediidae). AB - Six species of the mud-shrimp genus Axianassa Schmitt, 1924, herein placed in the Laomediidae, are reported from Panama, five species from the Pacific coast and one species from the Caribbean coast. Axianassa mineri Boone, 1931 and A. canalis Kensley & Heard, 1990, both originally described from the Pacific coast of Panama, are reported from new Panamanian localities, with the former species also reported from a new locality on the Pacific coast of Mexico. Additional illustrations complete the original descriptions of these two species. The recently described A. darrylfelderi Anker & Lazarus, 2015, previously known only from the type material from the Pacific coast of Colombia, is reported for the first time from Panama, whereas A. jamaicensis Kensley & Heard, 1990, previously known only from Jamaica, is reported for the first time from the Caribbean coast of Panama. Two species, viz. A. linda sp. nov. and A. christyi sp. nov., are described as new based on material from the Azuero Peninsula and the Las Perlas Archipelago, on the Pacific coast of Panama. Colour photographs are provided for all six species. A revised key to the 13 presently known species of Axianassa is provided, in addition to some taxonomic remarks on the genus and a justification for its placement in the family Laomediidae rather than Axianassidae. PMID- 27394903 TI - Revalidation of the Brazilian genus Discocyrtanus, with description of two new species (Opiliones: Gonyleptidae: Pachylinae). AB - The genus Discocyrtanus Roewer, 1929, is herein revalidated from the synonymy of Discocyrtus Holmberg, 1878, to include besides the type species Discocyrtanus goyazius Roewer, 1929, four other Brazilian species, two of them new Discocyrtanus bugre sp. nov. and Discocyrtanus tocantinensis sp. nov.-and two newly transferred from Discocyrtus: Discocyrtanus oliverioi (H. Soares, 1945) comb. nov., and Discocyrtanus pertenuis (Mello-Leitao, 1935) comb. nov. Three species, Discocyrtus pectinifemur Mello-Leitao, 1937, Discocyrtus fimbriatus Mello-Leitao, 1939, and Discocyrtus canalsi Roewer, 1943, are considered junior subjective synonyms of Discocyrtanus pertenuis comb. nov.. A mix-up between labeling of original illustrations of two species of Discocyrtus described by Mello-Leitao is noted. PMID- 27394904 TI - Update on the Brazilian coastal species of Bledius Leach (Coleoptera: Staphylinidae: Oxytelinae) with the description of two new species. AB - Based on the paratype of Bledius caribbeanus, its distribution is corrected, not occurring in Brazil, and its morphology is compared to B. hermani; two new Bledius species from the coast of Brazil are described; B. externus is redescribed and here for the first time recorded in Brazil and the key to identification of Brazilian coastal Bledius is updated. PMID- 27394905 TI - A new genus of mellitid sand dollar (Echinoidea: Mellitidae) from the eastern Pacific coast of the Americas. AB - Lanthonia gen. nov. Coppard 2016 is a genus of clypeasteroid sand dollar whose members inhabit shallow, sandy waters from Mexico (including the Gulf of California) to Colombia in the tropical and subtropical eastern Pacific. Lanthonia includes Lanthonia longifissa (Michelin, 1858) and Lanthonia grantii (Mortensen, 1948), with L. longifissa hereby designated as the type species. Both L. longifissa and L. grantii were previously placed in the genus Mellita (L. Agassiz, 1841). However, levels of genetic divergence between a lineage containing L. longifissa and L. grantii and a lineage containing all other species of Mellita, including the type species M. quinquiesperforata (Leske, 1778), indicate genus level differentiation. The systematic interpretation of this group also supports the designation of this new genus as it allows the tree topology to be recovered from the nomenclature and clarifies the historical biogeography of these clades. This has resulted in members of both lineages today being sympatric in the eastern Pacific. Members of Lanthonia are morphologically differentiated from the type species of Mellita and all Pacific Mellita in having very narrow ambulacral regions between the food grooves and the ambulacral lunules on the oral surface, these being very broad in both M. quinquiesperforata and M. notabilis. The dentation of the bidentate pedicellariae also differentiate these genera, with small peripheral teeth present along the edge of the blade in species of Lanthonia and one to three enlarged intersecting teeth present distally in all species of Mellita. PMID- 27394906 TI - Hoplitis (Hoplitis) galichicae spec. nov., a new osmiine bee species from Macedonia with key to the European representatives of the Hoplitis adunca species group (Megachilidae, Osmiini). AB - Hoplitis (Hoplitis) galichicae spec. nov., a new European osmiine bee species belonging to the Hoplitis adunca species group (Osmiini) is described and diagnosed. It is currently known only from the Galichica mountain range in southwestern Macedonia. Analysis of pollen contained in the metasomal scopae revealed that all females of the type series collected pollen on the flowers of Sedum (Crassulaceae), which is unexpected as most other members of the Hoplitis adunca species group are oligolectic or mesolectic on flowers of Boraginaceae and/or Fabaceae. An identification key including all European representatives of the Hoplitis adunca species group is given. PMID- 27394907 TI - Coleophora ericarnella Baldizzone, a new species of the C. pyrrhulipennella group (Lepidoptera: Coleophoridae) from the South-Eastern Alps. AB - Coleophora ericarnella Baldizzone, n. sp. is described from the East-Central Alps region (Italy and Slovenia). It belongs to the C. pyrrhulipennella group. Its larval host plant is Erica carnea (Ericaceae). The adult habitus and genitalia as well as its larval case are illustrated and compared with those of Coleophora pulchripennella Baldizzone, 2011 and C. pyrrhulipennella Zeller, 1849. DNA barcodes also distinguish all three species from each other in congruence with genitalia morphology. PMID- 27394908 TI - Notes on the genus Homogryllacris Liu, 2007 (Orthoptera: Gryllacrididae: Gryllacridinae) with description of two new species from China. AB - Two new species of the genus Homogryllacris Liu, 2007 are described and illustrated, i.e. Homogryllacris brevipenna sp. nov. (type locality: Yunnan), Homogryllacris curvicauda sp. nov. (type locality: Guangxi). A key to the species, additional bionomics and a distribution map for the genus Homogryllacris are provided. All material examined is deposited in the Museum of Hebei University. PMID- 27394909 TI - An annotated catalog of the Iranian Cimicidae and Largidae (Hemiptera: Heteroptera) and in memoriam Carl Walter Schaefer (1934-2015). AB - The Iranian fauna of the Cimicidae and Largidae (Hemiptera: Heteroptera) is summarized in this paper. In total, 2 species from 2 genera of Cimicidae and single species of Largidae are listed. PMID- 27394910 TI - The Impact of Interleukin-18 and High-Mobility Group Box 1 Protein Signaling in Aortic Valve Calcification. PMID- 27394912 TI - The association of asthma, total IgE, and blood lead and cadmium levels. PMID- 27394911 TI - Assessment of the myelin water fraction in rodent spinal cord using T2-prepared ultrashort echo time MRI. AB - OBJECTIVE: Multi-component T2 relaxation allows for assessing the myelin water fraction in nervous tissue, providing a surrogate marker for demyelination. The assessment of the number and distribution of different T2 components for devising exact models of tissue relaxation has been limited by T2 sampling with conventional MR methods. MATERIALS AND METHODS: A T2-prepared UTE sequence was used to assess multicomponent T2 relaxation at 9.4 T of fixed mouse and rat spinal cord samples and of mouse spinal cord in vivo. For in vivo scans, a cryogenically cooled probe allowed for 78-um resolution in 1-mm slices. Voxel wise non-negative least square analysis was used to assess the number of myelin water-associated T2 components. RESULTS: More than one myelin water-associated T2 component was detected in only 12 % of analyzed voxels in rat spinal cords and 6 % in mouse spinal cords, both in vivo and in vitro. However, myelin water associated T2 values of individual voxels varied between 0.1 and 20 ms. While in fixed samples almost no components below 1 ms were identified, in vivo, these contributed 14 % of the T2 spectrum. No significant differences in MWF were observed in mouse spinal cord in vivo versus ex vivo measurements. CONCLUSION: Voxel-wise analysis methods using relaxation models with one myelin water associated T2 component are appropriate for assessing myelin content of nervous tissue. PMID- 27394913 TI - DNA demethylation of inflammasome-associated genes is enhanced in patients with cryopyrin-associated periodic syndromes. AB - BACKGROUND: Inflammasomes are cytosolic multiprotein complexes in macrophages. They assemble after infection- or stress-associated stimuli, activating both caspase-1-mediated inflammatory cytokine secretion and pyroptosis. Increased inflammasome activity resulting from gene mutations is related to monogenic autoinflammatory syndromes. However, variable penetrance among patients with the same gene mutations suggests involvement of additional mechanisms associated with inflammasome gene regulation. OBJECTIVE: We sought to investigate the role of DNA demethylation in activating inflammasome genes during macrophage differentiation and monocyte activation in healthy control subjects and patients with autoinflammatory syndrome. METHODS: Inflammasome-related genes were tested for DNA methylation and mRNA levels by using bisulfite pyrosequencing and quantitative RT-PCR in monocytes in vitro differentiated to macrophages and exposed to inflammatory conditions. The contribution of Tet methylcytosine dioxygenase 2 (TET2) and nuclear factor kappaB to DNA demethylation was tested by using chromatin immunoprecipitation, small interfering RNA-mediated downregulation, and pharmacologic inhibition. RESULTS: We observed that inflammasome-related genes are rapidly demethylated in both monocyte-to macrophage differentiation and on monocyte activation. Demethylation associates with increased gene expression, and both mechanisms are impaired when TET2 and nuclear factor kappaB are downregulated. We analyzed DNA methylation levels of inflammasome-related genes in patients with cryopyrin-associated periodic syndromes (CAPS) and familial Mediterranean fever, 2 archetypical monogenic autoinflammatory syndromes. Under the above conditions, monocytes from untreated patients with CAPS undergo more efficient DNA demethylation than those of healthy subjects. Interestingly, patients with CAPS treated with anti-IL-1 drugs display methylation levels similar to those of healthy control subjects. CONCLUSION: Our study is the first to demonstrate the involvement of DNA methylation-associated alterations in patients with monogenic autoinflammatory disease and opens up possibilities for novel clinical markers. PMID- 27394914 TI - Staphylococcal enterotoxin A-activated regulatory T cells promote allergen specific TH2 response to intratracheal allergen inoculation. AB - BACKGROUND: TH2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. OBJECTIVE: We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote TH2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a TH2-polarizing cytokine milieu. METHODS: Ovalbumin (OVA)-specific, staphylococcal enterotoxin A (SEA)-nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen nonspecific Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA specific CD4 T cells were then analyzed for IL-13 and IFN-gamma expression. SEA activated Treg cells were analyzed for the expression of the TH2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and TH2 differentiation in these mice were analyzed. RESULTS: SEA-activated Treg cells induced IL-13 but suppressed IFN-gamma expression in OVA-specific CD4 Tcon cells. SEA-activated Treg cells expressed IL 4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-specific T cells. CONCLUSION: SEA promoted TH2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells. PMID- 27394915 TI - Memory-guided force output is associated with self-reported ADHD symptoms in young adults. AB - Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental health disorder in childhood and persists into adulthood in up to 65 % of cases. ADHD is associated with adverse outcomes such as the ability to gain and maintain employment and is associated with an increased risk for substance abuse obesity workplace injuries and traffic accidents A majority of diagnosed children have motor deficits; however, few studies have examined motor deficits in young adults. This study provides a novel examination of visuomotor control of grip force in young adults with and without ADHD. Participants were instructed to maintain force production over a 20-second trial with and without real-time visual feedback about their performance. The results demonstrated that when visual feedback was available, adults with ADHD produced slightly higher grip force than controls. However, when visual feedback was removed, adults with ADHD had a faster rate of decay of force, which was associated with ADHD symptom severity and trait impulsivity. These findings suggest that there may be important differences in the way that adults with ADHD integrate visual feedback during continuous motor tasks. These may account for some of the motor impairments reported in children with ADHD. These deficits could result from (1) dysfunctional sensory motor integration and/or (2) deficits in short-term visuomotor memory. PMID- 27394916 TI - Indications for prophylactic osteosynthesis associated with curettage in benign and low-grade malignant primitive bone tumors of the distal femur in adult patients: a case series. AB - BACKGROUND: The aim of the study was to evaluate whether the use of preventive osteosynthesis after curettage in benign and primitive low-grade malignant bone tumor localized in the distal femur in adult patients provides sufficient mechanical stability to the system as to allow weight-bearing and reduce the risk of postoperative fracture. Additionally, lower limb function after curettage and preventive osteosynthesis was evaluated. MATERIALS AND METHODS: We analyzed twelve cases of benign and low-grade malignant bone lesions of the distal femur in adult patients treated in our orthopedic department between 2008 and 2011 with curettage, bone filling and preventive osteosynthesis. All patients were treated with curettage with the use of high-speed cutters, plus liquid nitrogen as local adjuvant in low-grade malignant lesions, and filling of the lesion with bone graft or allograft or acrylic cement, followed by osteosynthesis. RESULTS: No fractures or major complications were observed; good function of the knee was observed. CONCLUSION: We recommend preventive osteosynthesis after curettage in patients with very large lesions (>5 cm, >60 cm3) or high functional requirements, in obese patients, and when local adjuvants are used. LEVEL OF EVIDENCE: Level IV retrospective case-series study. PMID- 27394917 TI - Interactive Voice Response-An Innovative Approach to Post-Stroke Depression Self Management Support. AB - Automated interactive voice response (IVR) call systems can provide systematic monitoring and self-management support to depressed patients, but it is unknown if stroke patients are able and willing to engage in IVR interactions. We sought to assess the feasibility and acceptability of IVR as an adjunct to post-stroke depression follow-up care. The CarePartner program is a mobile health program designed to optimize depression self-management, facilitate social support from a caregiver, and strengthen connections between stroke survivors and primary care providers (PCPs). Ischemic stroke patients and an informal caregiver, if available, were recruited during the patient's acute stroke hospitalization or follow-up appointment. The CarePartner program was activated in patients with depressive symptoms during their stroke hospitalization or follow-up. The 3-month intervention consisted of weekly IVR calls monitoring both depressive symptoms and medication adherence along with tailored suggestions for depressive symptom self-management. After each completed IVR call, informal caregivers were automatically updated, and, if needed, the subject's PCP was notified. Of the 56 stroke patients who enrolled, depressive symptoms were identified in 13 (23 %) subjects. Subjects completed 74 % of the weekly IVR assessments. A total of six subjects did not complete the outcome assessment, including two non-study-related deaths. PCPs were notified five times, including two times for suicidal ideation and three times for medication non-adherence. Stroke patients with depressive symptoms were able to engage in an IVR call system. Future studies are needed to explore the efficacy of an IVR approach for post-stroke self-management and monitoring of stroke-related outcomes. PMID- 27394918 TI - Assessment the Exposure Level of Rare Earth Elements in Workers Producing Cerium, Lanthanum Oxide Ultrafine and Nanoparticles. AB - In order to assess occupational exposure level of 15 rare earth elements (REEs) and identify the associated influence, we used inductively coupled plasma mass spectrometry (ICP-MS) based on closed-vessel microwave-assisted wet digestion procedure to determinate the concentration of Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu in urinary samples obtained from workers producing ultrafine and nanoparticles containing cerium and lanthanum oxide. The results suggest that La and Ce were the primary component, together accounting for 97 % of total REEs in workers. The urinary levels of La, and Ce among the workers (6.36, 15.32 MUg.g-1 creatinine, respectively) were significantly enriched compared to those levels measured in the control subjects (1.52, 4.04 MUg.g-1 creatinine, respectively) (p < 0.05). This study simultaneously identified the associated individual factors, the results indicate that the concentrations in over 5 years group (11.64 +/- 10.93 for La, 27.83 +/- 24.38 for Ce) were significantly elevated compared to 1-5 years group (2.58 +/- 1.51 for La, 6.87 +/ 3.90 for Ce) (p < 0.05). Compared the urinary levels of La and Ce at the separation and packaging locations (9.10 +/- 9.51 for La, 22.29 +/- 21.01 for Ce) with the other locations (2.85 +/- 0.98 for La, 6.37 +/- 2.12 for Ce), the results show urinary concentrations were significantly higher in workers at separation and packaging locations (p < 0.01). Inter-individual variation in levels of La and Ce in urine is the result of multi-factorial comprehensive action. Further researches should focus on the multiple factors contributing to the REEs levels of the occupationally exposed workers. PMID- 27394919 TI - In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant. AB - It is generally accepted that, in conjunction with pharmacokinetics, the first order rate constant of target dissociation is a major determinant of the time course and duration of in vivo target occupancy. Here we show that the second order rate constant of target association can be equally important. On the basis of the commonly used mathematical models for drug-target binding, it is shown that a high target association rate constant can increase the (local) concentration of the drug, which decreases the rate of decline of target occupancy. The increased drug concentration can also lead to increased off-target binding and decreased selectivity. Therefore, the kinetics of both target association and dissociation need to be taken into account in the selection of drug candidates with optimal pharmacodynamic properties. PMID- 27394921 TI - Intrauterine vesicoamniotic shunting for fetal megacystis. AB - OBJECTIVE: To examine the outcome of fetuses with megacystis treated with vesicoamniotic shunting (VAS) from 14 weeks onward. METHODS: Retrospective review of all fetuses that received VAS at two centres from 2004 to 2012. RESULTS: 53 fetuses with megacystis were included in the study. Mean gestational age at diagnosis was 16.4 weeks. Mean gestational age at first shunt placement was 17.8 weeks. The first shunt placement was performed before 16 weeks in 18 (34 %) cases. The mean number of shunts was 1.38. Dislocation occurred in 35 (66 %). TOP was performed in 21 (39.6 %), intrauterine death occurred in two (3.8 %) and spontaneous abortion in three cases (5.7 %). Of the 27 (50.9 %) live births, 17 (32.1 %) infants survived. Normal renal function was present in 10 cases, 4 have compensated renal failure and 3 infants had renal transplantation. Oligohydramnios was significantly associated with non-survival and renal insufficiency. The gestational age at VAS was neither correlated with renal function after birth nor with the survival in our cohort. Conversely, the interval between first shunt placement and delivery was positively correlated with survival and normal renal function. The gestational age at delivery was significantly higher in survivors and those born with normal renal function. CONCLUSION: Despite intervention, the morbidity and mortality of megacystis is still high. We failed to demonstrate that early intervention is associated with an improved rate of normal renal function after birth. Oligohydramnios was the only parameter identifying fetuses with unfavourable outcome, while all other parameters were inconclusive. PMID- 27394920 TI - Atorvastatin inhibits the apoptosis of human umbilical vein endothelial cells induced by angiotensin II via the lysosomal-mitochondrial axis. AB - This study was aimed to evaluate lysosomes-mitochondria cross-signaling in angiotensin II (Ang II)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and whether atorvastatin played a protective role via lysosomal mitochondrial axis. Apoptosis was detected by flow cytometry, Hoechst 33342 and AO/EB assay. The temporal relationship of lysosomal and mitochondrial permeabilization was established. Activity of Cathepsin D (CTSD) was suppressed by pharmacological and genetic approaches. Proteins production were measured by western blotting. Our study showed that Ang II could induce the apoptosis of HUVECs in a dose-depended and time-depended manner. Exposure to 1 MUM Ang II for 24 h resulted in mitochondrial depolarization, cytochrome c release, and increased ROS production. Lysosomal permeabilization and CTSD redistribution into the cytoplasm occurred several hours prior to mitochondrial dysfunction. These effects were all suppressed by atorvastatin. Either pharmacological or genetic inhibition of CTSD preserved mitochondrial function and decreased apoptosis in HUVECs. Most importantly, we found that the protective effect of atorvastatin was significantly greater than pharmacological or genetic inhibition of CTSD. Finally, overexpression of CTSD without exposure to Ang II had no effect on mitochondrial function and apoptosis. Our data strongly suggested that Ang II induced apoptosis through the lysosomal-mitochondrial axis in HUVECs. Furthermore, atorvastatin played an important role in the regulation of lysosomes and mitochondria stability, resulting in an antagonistic role against Ang II on HUVECs. PMID- 27394922 TI - Liver abscess after endoscopic retrograde cholangiopancreatography with presence of Actinomyces naeslundii. PMID- 27394923 TI - Zinc transporters and signaling in physiology and pathogenesis. AB - Zinc (Zn) is an essential trace element that is vital in a wide range of cellular machineries because of its effect on the expression and activity of various transcription factors and enzymes. Zn deficiency disturbs Zn homeostasis and has pathogenic consequences, including growth retardation and immune impairment in mammals. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the distribution, storage, and intracellular and extracellular concentration of Zn. Recent reverse-genetic approaches using Zn transporter-deficient mice have revealed the physiological functions of specific Zn signaling axes (each formed by Zn and a Zn transporter) in various biological programs. In this review, we describe recent discoveries about the role of Zn transporters which facilitate cellular signaling through Zn uptake in physiology and pathogenesis, with particular focus on the influence of Zn signaling in systemic growth and immunity. PMID- 27394924 TI - Vitamin K and non-vitamin K antagonist oral anticoagulants for non-valvular atrial fibrillation in real-life. AB - BACKGROUND: Current guidelines recommend vitamin K antagonists (VKAs) or non vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). METHODS: We compared the clinical features of consecutive in- and out-patients with non-valvular AF newly treated with NOACs or on treatment with VKAs. RESULTS: Overall, 1314 patients newly-treated with NOACs and 1024 on treatment with VKAs were included in the study. The mean CHA2DS2-VASc score was 4.3+/-1.5 and 4.0+/-1.5 and the mean HAS BLED score was 2.8+/-1.2 and 2.2+/-1.1 in the two groups, respectively (both p<0.001). Hypertension, previous stroke, female gender, vascular diseases and previous bleeding were more prevalent in NOACs patients. Renal failure, age >=75years and congestive heart failure were more prevalent in VKAs patients. Among NOACs patients, 438 were given dabigatran, 463 rivaroxaban and 413 apixaban (33%, 35% and 31%, respectively). The mean CHA2DS2-VASc and HAS-BLED scores were higher in rivaroxaban or apixaban patients compared with dabigatran (both p<0.001) and VKAs patients (both p<0.001). A lower mean age was observed in patients newly-treated with dabigatran. Patients newly-treated with reduced doses of NOACs (599 patients, 45.5%) had a higher CHA2DS2-VASc (4.8+/-1.4 vs. 3.9+/-1.5 vs. 4.0+/-1.5) and HAS-BLED (2.9+/-1.1 vs. 2.8+/-1.2 vs. 2.2+/-1.1) scores compared with those treated with regular doses of NOACs or VKAs. CONCLUSION: Patients given rivaroxaban and apixaban in clinical practice have a higher thrombotic and hemorrhagic risk in comparison with patients given dabigatran or VKAs. A considerable proportion of patients receive reduced doses of NOACs. PMID- 27394925 TI - Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. AB - BACKGROUND AND AIMS: Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. MATERIALS AND METHOD: A total of 519 CKD pre dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively RESULTS: The mean age of the patients was 52.2+/-12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values). CONCLUSION: Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors. PMID- 27394926 TI - A new definition of health? An open letter of autochthonous peoples and medical anthropologists to the WHO. AB - Currently, for many practitioners (hospital and liberals) and researchers (including public health), the WHO definition of health is outdated: first it seems more utopian than pragmatic; then, it proves unsuitable for a large part of the world population. There is clearly a need to refine this definition or propose additional criteria to be more relevant or discriminating. In this perspective, what can indigenous people offer in the elaboration of a new definition of health? In this article, leaders or representatives of autochthonous peoples, anthropologists and physicians from many cultural origins (Amazonia, Patagonia, Papua New-Guinea, Inuit, North-American Indian, sub-Saharan Africa, India, China, Melanesia and Polynesia) have tried to identify and explain several key concepts that WHO should reintegrate into its new definition of health: human equilibrium in nature, accepted spirituality and adaptation. On the sidelines of the application of COP21 decisions that should give back to man his place into the environment, autochthonous people leaders, anthropologists and MDs explain why these three concepts are fundamental and universal health determinants, and need to be included in a new WHO definition of health. PMID- 27394928 TI - Predictors of mortality in sepsis. PMID- 27394927 TI - Candidemia and invasive candidiasis in adults: A narrative review. AB - Candidemia and invasive candidiasis are major causes of morbidity and mortality, and their incidence is increasing because of the growing complexity of patients. Five species of Candida (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei) account for more than 90% of all diagnosed cases, but their relative frequency varies depending on the population involved, geographical region, previous anti-fungal exposure, and patient age. The best evidence regarding the anti-fungal treatment for invasive candidiasis comes from randomized controlled trials in which more than 85% of the recruited patients had candidemia. In the case of less frequent forms of invasive candidiasis, the recommendations are based on retrospective studies, meta analyses (when available) and experts' opinions. A pre-emptive approach based on biomarkers and clinical rules is recommended because of the high rate of infection-related mortality among critically ill patients. PMID- 27394929 TI - Prevalence of intimate partner violence in Spain: A national cross-sectional survey in primary care. AB - OBJECTIVES: (1) To analyze the prevalence of Intimate Partner Violence by types. (2) To examine the relationship between sociodemographic characteristics and Intimate Partner Violence. DESIGN: Cross-sectional study using a self administered questionnaire. SETTING: Primary Healthcare centers in Spain. PARTICIPANTS: 10,322 women (18-70 years) attending Primary Healthcare centers. MAIN MEASUREMENTS: A compound index was calculated based on frequency, types, and duration of Intimate Partner Violence. Multivariable adjusted logistic regression models were used to identify the sociodemographic factors, which were independently associated with each Intimate Partner Violence category. RESULTS: The prevalence of Intimate Partner Violence was 24.8%. For the physical only category, no differences were observed regarding education or employment status, and women with the highest income have less risk. For the psychological only category, no differences were observed according to the income level. The risk increases as the education level decreases, and the greatest frequency of only psychological Intimate Partner Violence was observed in women who were unemployed or students. For both the physical and psychological category of Intimate Partner Violence, a clear risk increase is observed as income and education levels decrease. Retired women showed the highest frequency of this violence category. CONCLUSION: The results show that Intimate Partner Violence affects women of all social strata, but the frequency and Intimate Partner Violence category will vary according to the socio-economic. PMID- 27394930 TI - The cholinergic immune regulation mediated by a novel muscarinic acetylcholine receptor through TNF pathway in oyster Crassostrea gigas. AB - Muscarinic receptors, which selectively take muscarine as their ligand, are critical for the immunological and physiological processes in animals. In the present study, the open region frame (ORF) of a homologue of muscarinic acetylcholine (ACh) receptor (mAChR) was amplified from oyster Crassostrea gigas (named as CgmAChR-1), whose full length was 1983 bp and the protein it encoded contained 660 amino acids with a seven transmembrane region. Phylogeny analysis suggested that CgmAChR-1 shared homology with M5 muscarinic receptor found in invertebrates including Habropoda laboriosa, Acromyrmex echinatior and Echinococcus granulosus. After cell transfection of CgmAChR-1 into HEK293T cells and ACh incubation, the level of intracellular Ca(2+) and cAMP increased significantly (p < 0.05). Such trend could be reverted with the addition of M3 and M5 muscarinic receptor antagonists DAMP and DAR. The CgmAChR-1 transcripts were ubiquitously detectable in seven different tissues with the maximal expression level in adductor muscle. When the oysters received LPS stimulation, CgmAChR-1 mRNA expression in haemocyte was increased to the highest level (6.05 fold, p < 0.05) at 24 h, while blocking CgmAChR-1 using receptor antagonists before LPS stimulation promoted the expression of oyster TNF, resulting in the increase of haemocyte apoptosis index. These results suggested that CgmAChR-1 was the key molecule in cholinergic neuroendocrine-immune system contributing to the regulation of TNF expression and apoptosis process. PMID- 27394931 TI - The individual and combined effects of phenmetrazine and mgluR2/3 agonist LY379268 on the motivation to self-administer cocaine. AB - BACKGROUND: The US Food and Drug Administration has not approved a treatment for cocaine addiction, possibly due in part to the fact that repeated cocaine use results in dysregulation of multiple neurotransmitter systems, including glutamate and dopamine, and an emergence of increased negative affective states and heightening motivation to take cocaine despite negative consequences. We used a combination therapy approach to assess whether modulation of both glutamate and dopamine transmission would reduce the motivation to self- administer cocaine compared to modulation of either system alone. METHODS: The metabotropic glutamate 2/3 receptor agonist, LY379268, and the monoamine releaser, phenmetrazine, were used to assess their individual and combined ability to decrease the reinforcing efficacy of cocaine because they modulate glutamate and dopamine levels, respectively. Cocaine breakpoints and cocaine intake was assessed, using a progressive ratio schedule, at baseline in three groups based on dose of cocaine (0.19, 0.38, 0.75mg/kg/infusion), and following LY379268 (0.03 or 0.30mg/kg; i.p.), phenmetrazine (25mg/kg/day; osmotic minipump), and a combination of the two drugs. RESULTS: LY379268 and phenmetrazine alone reduced breakpoints for all doses of cocaine. The combination of the two drugs showed a concerted effect in reducing breakpoints for all doses of cocaine, with the lowest dose of cocaine reduced by as much as 70%. CONCLUSIONS: These data support combination therapy of dopamine and glutamate systems as an effective means to reduce the motivation to take cocaine since a combination of drugs can address neurobiological dysfunction in multiple neurotransmitter systems compared to therapies using single drugs. PMID- 27394932 TI - Placebo-controlled evaluation of a bioengineered, cocaine-metabolizing fusion protein, TV-1380 (AlbuBChE), in the treatment of cocaine dependence. AB - BACKGROUND: TV-1380 (AlbuChE) is a novel recombinant fusion protein of mutated butyrylcholinesterase (BChE) that has increased catalytic efficiency for cocaine metabolism compared to wild-type BChE. METHODS: Intra-muscular injections of TV 1380 (150mg or 300mg) or placebo were administered once weekly to participants (n=66-69 per group) in a randomized, double-blind study to evaluate the ability of TV-1380 to facilitate abstinence in treatment-seeking, cocaine-dependent individuals. The primary endpoint was the proportion of participants achieving abstinence from cocaine during the last three weeks of the 12 week treatment phase, based on daily self-report of "no use" confirmed by urine testing. RESULTS: Although there were no significant differences between the TV-1380 treatment groups and placebo for the primary endpoint, 6% of participants in the 150mg and 300mg TV-1380 groups and no participants in the placebo group achieved abstinence. For the only declared secondary endpoint, there was a dose-dependent increase in the group mean percentage of urine samples testing negative for cocaine metabolites during weeks 5-12 (8.1% and 14.6% for the 150mg and 300mg TV 1380 groups, respectively, compared to 4.7% for the placebo group; p=0.0056 for 300mg vs. placebo). No meaningful differences in adverse events were seen between treatment groups. CONCLUSIONS: While the apparent reduction in cocaine use may be of insufficient magnitude to justify further trials of TV-1380 in cocaine dependence, the results argue for development of improved enzymes with greater catalytic activity. PMID- 27394933 TI - Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans. AB - BACKGROUND: Cannabis is a commonly used drug and studies have shown that a significant portion of the variation in cannabis use disorders (CUDs) is heritable. Five genes known to play a role in the endocannabinoid system and CUDs were examined in a community sample of young adult Mexican Americans (MAs): CNR1, MGLL, FAAH, DAGLA, and DAGLB. METHODS: Gene-based tests were run to test for association between each gene and two DSM-5 cannabis phenotypes. Subsequent linear regressions were run in PLINK using an additive model to determine which single nucleotide polymorphisms (SNPs) were driving the association. RESULTS: FAAH was significantly associated with DSM-5 cannabis use disorder group count (DSM-5 CUD) using a gene-based test (p=0.0035). This association survived Bonferroni correction for multiple testing at p<0.004. Post hoc analyses suggested this association was driven by two common (minor allele frequency >5%) SNPs in moderate linkage disequilibrium, rs324420 and rs4141964, at p=0.0014 and p=0.0023, respectively. In both cases the minor allele increased risk for DSM-5 CUD. CONCLUSIONS: Genetic variation in FAAH was associated with DSM-5 CUD in MAs. This association was primarily driven by the missense SNP rs324420. In vitro work has provided evidence that the risk allele generates an enzyme with decreased expression and cellular stability. Although this SNP has been previously associated with substance use in the literature, this is the first association in a young adult MA sample. PMID- 27394934 TI - National trends in alcohol pharmacotherapy: Findings from an Australian claims database. AB - BACKGROUND: Although the efficacy of alcohol pharmacotherapy has been widely investigated, little is known about real-world prescription patterns. Population based dispensing data can provide an understanding of prescription patterns and characteristics of treatment in nonexperimental settings. METHODS: A retrospective cohort study of patients (aged 15-84) treated with acamprosate or naltrexone between July 2009 and June 2013 was conducted using dispensing claims from the Australian Pharmaceutical benefits Scheme Database. Only individuals with prescriptions from September 2009 onwards were included. RESULTS: We identified 61,904 individuals (40% female, 32% in 35-44 age bracket,) with a total number of 198,247 dispensings. There were 23,452 naltrexone-treated and 38,452 acamprosate-treated patients. For naltrexone, 42% of initial dispenses were followed by a second dispense with only 25% receiving at least 3 months of treatment. For acamprosate, 28% of dispenses were followed by a third dispense with only 15% receiving at least 3 months of treatment. Patients in older age groups were more likely to be dispensed a repeat script than those in younger age groups (e.g., for the 75-84 vs 15-24 age bracket OR's=2.27 and 2.98 for naltrexone and acamprosate respectively). CONCLUSION: Current national guidelines in Australia recommend alcohol pharmacotherapy for a minimum period of 3 months yet only 15-25% are receive this duration of treatment. Naltrexone-treated patients were more likely to return for a second and third dispense than acamprosate-treated patients. Prevalence and prescribing patterns change with age. PMID- 27394935 TI - The IFIC Foundation Food & Health Survey 2015: 10-Year Trends and Emerging Issues. PMID- 27394937 TI - Heritability of metabolic response to the intravenous glucose tolerance test in German Holstein Friesian bulls. AB - Selection for improved health and welfare in farm animals is of increasing interest worldwide. Peripartum energy balance is a key factor for pathogenesis of diseases in dairy cows. The intravenous glucose tolerance test (ivGTT) can be used to study the metabolic response to a glucose stimulus. The aim of this study was to estimate heritability of ivGTT traits in German Holstein bulls. A total of 541 Holstein bulls aged 7 to 17 mo from 2 breeding stations were subjected to the ivGTT. Serum glucose concentrations were measured at 0, 7, 14, 21, 28, 35, 42, 49, 56, and 63 min relative to glucose infusion. The maximum increase in blood glucose concentration, glucose area equivalent, and blood glucose half-life period were calculated. Heritabilities were estimated using a univariate animal model including station-year-season and age as fixed effects, and animal additive genetic and residual as random effects. The estimated heritabilities were 0.19 for fasting glucose concentration, 0.43 for glucose area equivalent, 0.40 for glucose half-life period, 0.14 for the peak glucose concentration, and 0.12 for the maximum increase of blood glucose concentration. Correlations between ivGTT traits and breeding values for milk yield and composition were not found. The results indicate that heritability for response to glucose is high, which warrants further investigation of this trait for genetic improvement of metabolic disorders. Research is necessary to determine the target levels of ivGTT traits and potential associations between ivGTT traits in breeding bulls and periparturient diseases in their offspring. PMID- 27394936 TI - Reliability of 24-Hour Dietary Recalls as a Measure of Diet in African-American Youth. AB - BACKGROUND: Although it is a common practice to estimate dietary intake using three random 24-hour dietary recalls, some studies have suggested up to nine may be necessary to reliably estimate usual intake in youth. Given the resulting increase in resources and participant burden, more research is needed to determine whether this method is reliable, particularly in African-American youth at increased risk for obesity and other chronic diseases. OBJECTIVE: This study estimated the reliability with which 24-hour dietary recalls measure energy, fat, fruit, and vegetable intake in African-American youth and examined how reliability changes as a function of the number of recalls. DESIGN: This study used cross-sectional data collection across three studies. PARTICIPANTS/SETTING: Participants were African-American youth (n=456, mean+/-standard deviation age 13.28+/-1.86 years, 64% were girls, mean+/-standard deviation body mass index [calculated as kg/m(2)] 31.45+/-7.94) who completed random 24-hour dietary recalls (67% completed three) conducted by research assistants using the Automated Self-Administered 24-Hour recall system (n=258) or registered dietitian nutritionists using the Nutrition Data System for Research (n=198). MAIN OUTCOME MEASURES/STATISTICAL ANALYSES: Estimates provided by multilevel models were used to calculate the proportion of variance accounted for between individuals and the reliability of means within individuals as a function of the number of recalls. RESULTS: Reliability estimates for assessing dietary outcomes using one to three recalls ranged from 11% to 62%. To achieve 80% reliability, the following number of recalls would need to be conducted: 8 for energy intake, 13 for fat intake, 21 to 32 for fruit intake, and 21 to 25 for vegetable intake. CONCLUSIONS: The common practice of assessing dietary intake with three recalls does so with low reliability in African-American youth. Until more objective methods for reliably estimating usual intake are developed, researchers who choose to use 24-hour dietary recalls are encouraged to include estimates of the measure's reliability in a priori power calculations for improved decision making regarding the number of observations and/or sample size. PMID- 27394938 TI - Evaluation of different methods to detect microbial hygiene indicators relevant in the dairy industry. AB - It is estimated that 19% of the total food loss from retail, food service, and households comes from dairy products. A portion of this loss may be attributed to premature spoilage of products due to lapses in sanitation and postpasteurization contamination at the processing level. Bacterial groups including coliforms, Enterobacteriaceae (EB), and total gram-negative organisms represent indicators of poor sanitation or postpasteurization contamination in dairy products worldwide. Although Petrifilms (3M, St. Paul, MN) and traditional selective media are commonly used for the testing of these indicator organism groups throughout the US dairy industry, new rapid methods are also being developed. This project was designed to evaluate the ability of different methods to detect coliforms, EB, and other gram-negative organisms isolated from various dairy products and dairy processing environments. Using the Food Microbe Tracker database, a collection of 211 coliform, EB, and gram-negative bacterial isolates representing 25 genera associated with dairy products was assembled for this study. We tested the selected isolates in pure culture (at levels of approximately 15 to 300 cells/test) to evaluate the ability of 3M Coliform Petrifilm to detect coliforms, 3M Enterobacteriaceae Petrifilm, violet red bile glucose agar, and an alternative flow cytometry-based method (bioMerieux D-Count, Marcy-l'Etoile, France) to detect EB, and crystal violet tetrazolium agar to detect total gram-negative organisms. Of the 211 gram-negative isolates tested, 82% (174/211) had characteristic growth on crystal violet tetrazolium agar. Within this set of 211 gram-negative organisms, 175 isolates representing 19 EB genera were screened for detection using EB selective/differential testing methods. We observed positive results for 96% (168/175), 90% (158/175), and 86% (151/175) of EB isolates when tested on EB Petrifilm, violet red bile glucose agar, and D-Count, respectively; optimization of the cut-off thresholds for the D-Count may further improve its sensitivity and specificity, but will require additional data and may vary in food matrices. Additionally, 74% (129/175) of the EB isolates tested positive as coliforms. The data obtained from this study identify differences in detection between 5 microbial hygiene indicator tests and highlight the benefits of EB and total gram-negative testing methods. PMID- 27394939 TI - Prepartum concentrate supplementation of a diet based on medium-quality grass silage: Effects on performance, health, fertility, metabolic function, and immune function of low body condition score cows. AB - When cows with a "higher" body condition score (BCS) are oversupplied with energy during the dry period, postpartum energy balance is normally reduced, which can have a detrimental effect on immune competence and increase the infectious disease risk. However, within grassland-based systems higher yielding cows frequently have a low BCS at drying off. The effects on performance, health, and metabolic and immune functions of providing additional energy to cows with low BCS during the dry period is less certain. To address this uncertainty, 53 multiparous Holstein-Friesian cows (mean BCS of 2.5; 1-5 scale) were allocated to 1 of 2 treatments at dry-off: silage only or silage plus concentrates. Cows on the silage-only treatment were offered ad libitum access to medium-quality grass silage. Cows on the silage-plus-concentrate treatment were offered ad libitum access to a mixed ration comprising the same grass silage plus concentrates [in a 75:25 dry matter (DM) ratio], which provided a mean concentrate DM intake of 3.0kg/cow per day. Postpartum, cows were offered a common mixed ration comprising grass silage and concentrates (in a 40:60 DM ratio) for a 70-d period. Offering concentrates during the dry period increased DM intake, tended to increase energy balance, and increased body weight (BW) and BCS gain prepartum. Offering concentrates during the dry period increased BW and BCS loss postpartum and tended to increase milk fat percentage and serum nonesterified fatty acid concentration, but it did not affect postpartum DM intake, energy balance, and milk yield. Although the percentage of phagocytosis-positive neutrophils did not differ, neutrophils from cows on the silage-plus-concentrate treatment had higher phagocytic fluorescence intensity at 1 and 2 wk postpartum and higher phagocytic index at 1 wk postpartum. Serum haptoglobin concentrations and IFN-gamma production by pokeweed mitogen stimulated whole blood culture were unaffected by treatment, although haptoglobin concentrations increased and IFN-gamma production decreased peripartum. Offering concentrates during the dry period increased the incidence of lameness postpartum, although other health and fertility parameters were unaffected. In conclusion, supplementing low BCS cows with concentrates during the dry period had no effect on performance and fertility and resulted in a higher neutrophil phagocytic index at 1 wk postpartum and an increased incidence of lameness compared with offering cows a grass silage-only diet prepartum. PMID- 27394941 TI - Composition and functionality of whey protein phospholipid concentrate and delactosed permeate. AB - Whey protein phospholipid concentrate (WPPC) and delactosed permeate (DLP) are 2 coproducts of cheese whey processing that are currently underused. Past research has shown that WPPC and DLP can be used together as a functional dairy ingredient in foods such as ice cream, soup, and caramel. However, the scope of the research has been limited to 1 WPPC supplier. The objective of this research was to fully characterize a range of WPPC. Four WPPC samples and 1 DLP sample were analyzed for chemical composition and functionality. This analysis showed that WPPC composition was highly variable between suppliers and lots. In addition, the functionality of the WPPC varies depending on the supplier and testing pH, and cannot be correlated with fat or protein content because of differences in processing. The addition of DLP to WPPC affects functionality. In general, WPPC has a high water-holding capacity, is relatively heat stable, has low foamability, and does not aid in emulsion stability. The gel strength and texture are highly dependent on the amount of protein. To be able to use these 2 dairy products, the composition and functionality must be fully understood. PMID- 27394940 TI - Isolation and characterization of anti-inflammatory peptides derived from whey protein. AB - The present study was conducted to isolate and characterize anti-inflammatory peptides from whey protein hydrolysates using alcalase. Nine subfractions were obtained after sequential purification by ultrafiltration, Sephadex G-25 gel (GE Healthcare, Uppsala, Sweden) filtration chromatography, and preparative HPLC. Among them, subfraction F4e showed the strongest inhibitory activity on interleukin-1beta (IL-1beta), cyclooxygenase-2, and tumor necrosis factor-alpha (TNF-alpha) mRNA expression in lipopolysaccharide-induced RAW 264.7 mouse macrophages. Eight peptides, including 2 new peptides-Asp-Tyr-Lys-Lys-Tyr (DYKKY) and Asp-Gln-Trp-Leu (DQWL)-were identified from subfractions F4c and F4e, respectively, using ultra-high performance liquid chromatography-quadrupole-time of-flight mass spectrometry. Peptide DQWL showed the strongest inhibitory ability on IL-1beta, cyclooxygenase-2, and TNF-alpha mRNA expression and production of IL 1beta and TNF-alpha proteins at concentrations of 10 and 100MUg/mL, respectively. Additionally, DQWL treatment significantly inhibited nuclear factor-kappaB activation by suppressing nuclear translocation of nuclear factor-kappaB p65 and blocking inhibitor kappaB kinase phosphorylation and inhibitor kappaB degradation together with p38 mitogen-activated protein kinase activation. Our study suggests that peptide DQWL has anti-inflammatory potential; further confirmation using an in vivo model is needed. PMID- 27394942 TI - Effect of time of maize silage supplementation on herbage intake, milk production, and nitrogen excretion of grazing dairy cows. AB - The objective of this study was to evaluate the effect of feeding maize silage at different times before a short grazing bout on dry matter (DM) intake, milk production, and N excretion of dairy cows. Thirty-six Friesian * Jersey crossbred lactating dairy cows were blocked in 9groups of 4 cows by milk solids (sum of protein and fat) production (1.26+/-0.25kg/d), body weight (466+/-65kg), body condition score (4+/-0.48), and days in milk (197+/-15). Groups were then randomly assigned to 1 of 3 replicates of 3 treatments: control; herbage only, supplemented with 3kg of DM/cow of maize silage after morning milking approximately 9h before pasture allocation (9BH); and supplemented with 3kg of DM/cow of maize silage before afternoon milking approximately 2h before pasture allocation (2BH). Herbage allowance (above the ground level) was 22kg of DM/cow per day for all groups of cows. Cows were allocated to pasture from 1530 to 2030 h. Maize silage DM intake did not differ between treatments, averaging 3kg of DM/cow per day. Herbage DM intake was greater for control than 2BH and 9BH, and greater for 9BH than 2BH (11.1, 10.1, and 10.9kg of DM/cow per day for control, 2BH, and 9BH, respectively). The substitution rate (kilograms of herbage DM per kilograms of maize silage DM) was greater for 2BH (0.47) than 9BH (0.19). Milk solids production was similar between treatments (overall mean 1.2kg/cow per day). Body weight loss tended to be less for supplemented than control cows ( 0.95, -0.44, and -0.58kg/cow per day for control, 2BH, and 9BH, respectively). Nitrogen concentration in urine was not affected by supplementation or time of supplementation, but estimated urinary N excretion tended to be greater for control than supplemented cows when urinary N excretion estimated using plasma or milk urea N. At the time of herbage meal, nonesterified fatty acid concentration was greater for control than supplemented cows and greater for 9BH than 2BH (0.58, 0.14, and 0.26mmol/L for control, 2BH, and 9BH, respectively). Timing of maize silage supplementation relative to a short and intensive herbage meal can reduce the substitution rate and increase herbage DM intake of grazing dairy cows. PMID- 27394943 TI - Effect of calving process on the outcomes of delivery and postpartum health of dairy cows with unassisted and assisted calvings. AB - Welfare aspects of obstetrical assistance were studied in multiparous Holstein Friesian cows (n=176) with (1) unassisted calving in an individual pen (UCIP; n=42), (2) unassisted calving in a group pen (UCG; n=48), (3) assisted calving with appropriately timed obstetrical assistance (ACAP; n=50), and (4) assisted calving with inappropriately timed (premature) obstetrical assistance (ACIN; n=36). Duration of the stages of calving, the prevalence and the degree of dystocia, stillbirth ratio, newborn calf vitality, and the occurrence of postpartum health problems (i.e., retained placenta and vulvovaginal laceration) were recorded. The time from amniotic sac and hooves appearance to birth and the total duration of calving (from the onset of calving restlessness to delivery) were shorter for UCG cows than for any other groups. The overall incidence of dystocia was 31.3% in the calvings studied. The prevalence of dystocia was below 10% in cases of unassisted calvings. The proportion of severe dystocia was higher in ACIN cows than in ACAP cows (47.2 vs. 12.0%, respectively). The prevalence of stillbirths was the highest in ACIN calvings (22.2%), followed by ACAP, UCI, and UCG cows (8.0, 4.8, and 0.0%, respectively). The ACIN calves had lower vitality scores than calves born from ACAP, UCG, and UCIP dams immediately after delivery and 24h after birth. Although ACAP calves had lower vitality scores than UCG and UCIP calves at birth, a delayed recovery of vitality was mirrored by satisfactory vitality scores 24h after birth. Retained placenta and vulvovaginal laceration occurred more often with assisted dams (i.e., ACAP and ACIN animals) compared with UCIP cows with the highest prevalence in ACIN cows. In UCG cows, no injuries occurred in the vulva or vagina, and we noted only 4 cases of retained placenta (8.3%), proportions lower than in cows with unassisted calving in the maternity pen. Our results suggest that calving in a group might have benefits over calving in an individual pen in terms of calving ease, duration of the delivery process, and postpartum health of the dam vitality of her offspring. Premature obstetrical assistance leads to a high prevalence of dystocia, impairs postpartum health of the dam, and poses a potential risk to calf survival. PMID- 27394944 TI - Effects of extruding wheat dried distillers grains with solubles with peas or canola meal on ruminal fermentation, microbial protein synthesis, nutrient digestion, and milk production in dairy cows. AB - Our objective was to examine the effects of feeding coextruded and nonextruded supplements consisting of wheat dried distillers grains with solubles with peas (WDDGS-peas) or canola meal (WDDGS-CM) on ruminal fermentation, omasal flow, and production performance in Holstein cows. Eight cows (4 ruminally cannulated) were used in a replicated 4*4 Latin square with 28-d periods and a 2*2 factorial arrangement of dietary treatments. Dietary treatments were coextruded or nonextruded mixtures of WDDGS-peas and WDDGS-CM that were included in total mixed rations at 15.1% [dry matter (DM) basis]. Diet had no effect on DM intake. Milk yield was greater in cows fed coextruded diets compared with those fed nonextruded diets. Milk fat content was greater in cows fed nonextruded diets compared with those fed coextruded diets, but milk fat yield was greater in cows fed coextruded diets compared with those fed nonextruded diets. Milk yield tended to be greater and milk protein yield was greater in cows fed WDDGS-peas compared with those fed WDDGS-CM. Cows fed nonextruded diets had a greater milk urea-N concentration compared with those fed coextruded diets. Cows fed coextruded diets had greater ruminal digestion of DM and tended to have greater ruminal digestion of organic matter compared with those fed nonextruded diets. Total-tract digestibilities of organic matter, crude protein, ether extract, and starch were greater, whereas that of acid detergent fiber and neutral detergent fiber tended to be greater in cows fed coextruded compared with those fed nonextruded diets. Total-tract digestibility of ether extract was lower whereas that of starch was greater and that of crude protein tended to be greater in cows fed WDDGS-peas compared with those fed WDDGS-CM. Total N excretion and milk N efficiency were unaffected by diet. Ruminal NH3-N concentration tended to be greater in cows fed WDDGS-CM compared with those fed WDDGS-peas. Ruminal propionate concentration was greater whereas plasma urea-N concentration tended to be lower in cows fed coextruded compared with those fed nonextruded diets. Plasma glucose concentration was greater in cows fed diets containing WDDGS-CM compared with those fed diets containing WDDGS-peas, but the difference in plasma glucose concentration between WDDGS-CM and WDDGS-peas was greater in cows fed coextruded diets compared with those fed nonextruded diets. In summary, feeding coextruded compared with nonextruded supplements or WDDGS-peas compared WDDGS-CM increased yields of milk, fat, and protein. PMID- 27394945 TI - Technical note: Use of a digital and an optical Brix refractometer to estimate total solids in milk replacer solutions for calves. AB - The Brix refractometer is used on dairy farms and calf ranches for colostrum quality (estimation of IgG concentration), estimation of serum IgG concentration in neonatal calves, and nonsalable milk evaluation of total solids for calf nutrition. Another potential use is to estimate the total solids concentrations of milk replacer mixes as an aid in monitoring feeding consistency. The purpose of this study was to evaluate the use of Brix refractometers to estimate total solids in milk replacer solutions and evaluate different replacer mixes for osmolality. Five different milk replacer powders (2 milk replacers with 28% crude protein and 25% fat and 3 with 22% crude protein and 20% fat) were mixed to achieve total solids concentrations from approximately 5.5 to 18%, for a total of 90 different solutions. Readings from both digital and optical Brix refractometers were compared with total solids. The 2 types of refractometers' readings correlated well with one another. The digital and optical Brix readings were highly correlated with the total solids percentage. A value of 1.08 to 1.47 would need to be added to the Brix reading to estimate the total solids in the milk replacer mixes with the optical and digital refractometers, respectively. Osmolality was correlated with total solids percentage of the mixes, but the relationship was different depending on the type of milk replacer. The Brix refractometer can be beneficial in estimating total solids concentration in milk replacer mixes to help monitor milk replacer feeding consistency. PMID- 27394946 TI - Sensitive detection of Escherichia coli O157:H7 based on cascade signal amplification in ELISA. AB - In this study, cascade signal amplification in ELISA involving double-antibody sandwich ELISA and indirectly competitive ELISA was established to sensitively detect Escherichia coli O157:H7. In the double-antibody sandwich ELISA, a complex was formed comprising anti-E. coli O157:H7 polyclonal antibody, E. coli O157:H7, biotinylated anti-E. coli O157:H7 monoclonal antibody, streptavidin, and biotinylated beta-lactamase. Penicillin solution was then added into the ELISA well and hydrolyzed by beta-lactamase. Afterward, the penicillin solution was transferred to indirectly competitive ELISA. The concentration of penicillin can be sensitively detected in indirectly competitive ELISA. In the cascade signal amplification system, increasing the amount of added E. coli O157:H7 resulted in more beta-lactamase and less penicillin. The detection sensitivity of E. coli O157:H7, which was 20cfu/mL with the cascade signal amplification in ELISA, was 1,000-fold higher than that of traditional ELISA. Furthermore, the novel method can be used to detect E. coli O157:H7 in milk (2cfu/g). Therefore, this new signaling strategy will facilitate analyses of highly sensitive foodborne pathogens. PMID- 27394947 TI - Phenotypic and genetic effects of recessive haplotypes on yield, longevity, and fertility. AB - Phenotypes from the August 2015 US national genetic evaluation were used to compute phenotypic effects of 18 recessive haplotypes in Ayrshire (n=1), Brown Swiss (n=5), Holstein (n=10), and Jersey (n=2) cattle on milk, fat, and protein yields, somatic cell score (SCS), single-trait productive life (PL), daughter pregnancy rate (DPR), heifer conception rate (HCR), and cow conception rate (CCR). The haplotypes evaluated were Ayrshire haplotype 1, Brown Swiss haplotypes 1 and 2, spinal dysmyelination, spinal muscular atrophy, Weaver Syndrome, brachyspina, Holstein cholesterol deficiency, Holstein haplotypes 1 to 5, bovine leukocyte adhesion deficiency, complex vertebral malformation, mulefoot (syndactyly), and Jersey haplotypes 1 and 2. When causal variants are unknown and tests are based only on single nucleotide polymorphism haplotypes, it can sometimes be difficult to accurately determine carrier status. For example, 2 Holstein haplotypes for cholesterol deficiency have the same single nucleotide polymorphism genotype, but only one of them carries the causative mutation. Genotyped daughters of carrier bulls included in the analysis ranged from 8 for Weaver Syndrome to 17,869 for Holstein haplotype 3. Lactation records preadjusted for nongenetic factors and direct genomic values (DGV) were used to estimate phenotypic and genetic effects of recessive haplotypes, respectively. We found no phenotypic or genetic differences between carriers and noncarriers of Ayrshire or Brown Swiss defects. Several associations were noted for Holstein haplotypes, including fat and HCR for Holstein haplotype 0 carriers; milk, protein, SCS, PL, and fertility for Holstein haplotype 1; protein, PL, CCR, and HCR for Holstein haplotype 2; milk, protein, and fertility for Holstein haplotype 4; and protein yield and DPR for Holstein haplotype 5. There were no differences among bovine leukocyte adhesion deficiency carriers, but complex vertebral malformation affected fat yield and mulefoot carriers had higher SCS and lower PL DGV. Jersey haplotype 1 was not associated with any phenotypic effects, but we noted significant differences among DGV for fat, protein, PL, DPR, CCR, and HCR. Jersey haplotype 2 was associated only with lower phenotypic CCR. Effects of the recessive haplotypes on other traits studied generally were small even when significant. Almost $11 million of economic losses per year due to reduced fertility and perinatal calf death in the US population can be avoided by selecting mate pairs that will not produce affected embryos. Carrier animals may continue to be selected if the merit of their favorable alleles exceeds the loss from their recessive alleles, but carrier bulls can be generally avoided without reducing the average genetic merit of the sires available for mating. PMID- 27394948 TI - Short communication: Association of lying behavior and subclinical ketosis in transition dairy cows. AB - The objective of this study was to characterize the association of lying behavior and subclinical ketosis (SCK) in transition dairy cows. A total of 339 dairy cows (107 primiparous and 232 multiparous) on 4 commercial dairy farms were monitored for lying behavior and SCK from 14d before calving until 28 d after calving. Lying time, frequency of lying bouts, and average lying bout length were measured using automated data loggers 24h/d. Cows were tested for SCK 1*/wk by taking a blood sample and analyzing for beta-hydroxybutyrate; cows with beta hydroxybutyrate >=1.2mmol/L postpartum were considered to have SCK. Cases of retained placenta, metritis, milk fever, or mastitis during the study period were recorded and cows were categorized into 1 of 4 groups: healthy (HLT) cows had no SCK or any other health problem (n=139); cows treated for at least 1 health issue other than SCK (n=50); SCK (HYK) cows with no other health problems during transition (n=97); or subclinically ketotic plus (HYK+) cows that had SCK and 1 or more other health problems (n=53). Daily lying time was summarized by week and comparisons were made between HLT, HYK, and HYK+, respectively. We found no difference among health categories in lying time, bout frequency, or bout length fromwk -2 towk +4 relative to calving for first-lactation cows. Differences in lying time for multiparous cows were seen inwk +1, when HYK+ cows spent 92+/-24.0 min/d more time lying down than HLT cows, and duringwk +3 and +4 when HYK cows spent 44+/-16.7 and 41+/-18.9 min/d, respectively, more time lying down than HLT cows. Increased odds of HYK+ were found to be associated with higher parity, longer dry period, and greater stall stocking density inwk -1 and longer lying time duringwk +1. When comparing HYK to HLT cows, the same variables were associated with odds of SCK; however, lying time was not retained in the final model. These results suggest that monitoring lying time may contribute to identifying multiparous cows experiencing SCK with another health problem after calving, but may not be useful in the early detection of SCK. PMID- 27394949 TI - Sensory profile development of Oaxaca cheese and relationship with physicochemical parameters. AB - A sensory profile of Oaxaca cheese was developed. To represent both industrial and artisanal Oaxaca cheese, 3 types of cheese were manufactured under controlled conditions: 2 with pasteurized milk using a mesophilic lactic acid bacteria culture (Lactococcus lactis ssp. lactis and L. lactis ssp. cremoris) and a thermophilic lactic acid bacteria culture (Streptococcus salivarius ssp. thermophilus), and a third with naturally acidified raw milk. The cheeses were evaluated by a panel of 11 trained judges. Additionally, chemical composition and instrumental color parameters were determined, an instrumental texture profile analysis was performed, and volatile compounds were identified by solid-phase microextraction coupled with gas chromatography/mass spectrometry. The sensory profile developed includes 43 descriptors, of which 13 are discriminant among these 3 cheese types. Descriptors include visual attribute waxy; tactile (manual) attributes moist and oily; orthonasal aroma attributes empyreumatic and cow; basic taste attribute salty; mouth texture attributes chewable, gummy, adherent, fibrous, moist, and fatty; and auditory attribute squeaky. A strong correlation was found between specific sensory data and physicochemical parameters measured by instrumental and chemical methods. PMID- 27394950 TI - Hypothalamic-pituitary-adrenal and cardiac autonomic responses to transrectal examination differ with behavioral reactivity in dairy cows. AB - Behavior, hypothalamic-pituitary-adrenal axis, and cardiac autonomic nervous system (ANS) activity were evaluated in response to transrectal examination in nonlactating Holstein-Friesian cows with different behavioral reactivity. According to behavioral reactions shown to the procedure of fixing the heart rate (HR) monitors, the 20 cows with the highest and the 20 cows with the lowest behavioral reactivity were involved in the study (high responder, n=20; and low responder, n=20, respectively). Activity of the ANS was assessed by HR and HR variability parameters. Blood and saliva were collected at 5 min before (baseline) and 0, 5 10, 15, 20, 30, 40, 60, and 120 min after the examination to determine cortisol concentrations. The examination lasted for 5 min. Cardiac parameters included HR, the root mean square of successive differences between the consecutive interbeat intervals, the high frequency (HF) component of heart rate variability, and the ratio between the low frequency (LF) and HF parameter (LF/HF). Following the examination, peak plasma and saliva cortisol levels and the amplitude of the plasma and saliva cortisol response were higher in high responder cows than in low responders. Areas under the plasma and saliva cortisol response curves were greater in high responder cows. Plasma and salivary cortisol levels correlated significantly at baseline (r=0.91), right after examination (r=0.98), and at peak levels (r=0.96). Area under the HR response curve was higher in low responder cows; however, maximum HR and the amplitude of the HR response showed no differences between groups. Minimum values of both parameters calculated for the examination were higher in high responders. Following the examination, response parameters of root mean square of successive differences and HF did not differ between groups. The maximum and the amplitude of LF/HF response and area under the LF/HF response curve were lower in low responder cows, suggesting a lower sympathetic activation of the ANS. Although changes in behaviors indicated that the procedure was painful for the animals, no differences were observed either in vocalization or in attendant behavior between groups during the examination. Our results demonstrate that behaviorally more reactive animals exhibit increased plasma and salivary cortisol concentrations and higher cardiac autonomic responsiveness to transrectal examination than less reactive cows. Salivary cortisol may substitute for plasma cortisol when assessing response of cattle to stress. PMID- 27394951 TI - Supplementation of essential fatty acids to Holstein calves during late uterine life and first month of life alters hepatic fatty acid profile and gene expression. AB - Linoleic acid is an essential dietary fatty acid (FA). However, how the supplementation of linoleic acid during uterine and early life may modify the FA profile and transcriptome regulation of the liver, and performance of preweaned dairy calves is unknown. Our objective was to evaluate the effect of supplementation of essential FA to Holstein calves during late uterine and early life on their hepatic FA profile and global gene expression at 30 d of age. During the last 8 wk of pregnancy, Holstein cattle (n=96) were fed either no fat supplement (control), a saturated FA supplement enriched with C18:0, or an unsaturated FA supplement enriched with linoleic acid. Male calves (n=40) born from these dams were fed a milk replacer (MR) with either low (LLA) or high linoleic acid (HLA) concentration as the sole feedstuff during the first 30 d. Liver biopsy was performed at 30 d of age, and microarray analysis was performed on 18 liver samples. Total concentration of FA in liver were greater in calves fed LLA compared with those fed HLA MR (8.2 vs. 7.1%), but plasma concentrations of total FA did not differ due to MR diets. The FA profiles of plasma and liver of calves were affected differently by the prepartum diets. Specifically, the FA profile in liver was affected moderately by the feeding of fat prepartum, but the profiles did not differ due to the type of FA fed prepartum. The type of MR fed during the first 30 d of life had major effects on both plasma and liver FA profiles, resembling the type of fat fed. Plasma and liver of calves fed LLA MR had greater percentage of medium-chain FA (C12:0 and C14:0), whereas plasma and liver from calves fed HLA MR had greater percentages of linoleic and alpha linolenic acids. Dams fed fat or a specific type of FA modified the expression of some genes in liver of calves, particularly those genes involved in biological functions and pathways related to upregulation of lipid metabolism and downregulation of inflammatory responses. Feeding HLA instead of LLA MR modified the expression of hepatic genes, including genes predicted to decrease infections and to increase lipid utilization and protein synthesis. Research evaluating the effect of FA supplementation during uterine and neonatal life on the future productivity of the neonate is warranted. PMID- 27394952 TI - Evaluation of 2 portable ion-selective electrode meters for determining whole blood, plasma, urine, milk, and abomasal fluid potassium concentrations in dairy cattle. AB - Two low-cost ion-selective electrode (ISE) handheld meters (CARDY C-131, LAQUAtwin B-731; Horiba Ltd., Albany, NY) have recently become available for measuring the potassium concentration ([K(+)]) in biological fluids. The primary objective of this study was to characterize the analytical performance of the ISE meters in measuring [K(+)] in bovine whole blood, plasma, urine, milk, and abomasal fluid. We completed 6 method comparison studies using 369 whole blood and plasma samples from 106 healthy periparturient Holstein-Friesian cows, 138 plasma samples from 27 periparturient Holstein-Friesian cows, 92 milk samples and 204 urine samples from 16 lactating Holstein-Friesian cows, and 94 abomasal fluid samples from 6 male Holstein-Friesian calves. Deming regression and Bland-Altman plots were used to characterize meter performance against reference methods (indirect ISE, Hitachi 911 and 917; inductively coupled plasma-optical emission spectroscopy). The CARDY ISE meter applied directly in plasma measured [K(+)] as being 7.3% lower than the indirect ISE reference method, consistent with the recommended adjustment of +7.5% when indirect ISE methods are used to analyze plasma. The LAQUAtwin ISE meter run in direct mode measured fat-free milk [K(+)] as being 3.6% lower than the indirect ISE reference method, consistent with a herd milk protein percentage of 3.4%. The LAQUAtwin ISE meter accurately measured abomasal fluid [K(+)] compared to the indirect ISE reference method. The LAQUAtwin ISE meter accurately measured urine [K(+)] compared to the indirect ISE reference method, but the median measured value for urine [K(+)] was 83% of the true value measured by inductively coupled plasma-optical emission spectroscopy. We conclude that the CARDY and LAQUAtwin ISE meters are practical, low-cost, rapid, accurate point-of-care instruments suitable for measuring [K(+)] in whole blood, plasma, milk, and abomasal fluid samples from cattle. Ion-selective electrode methodology is not suitable for measuring [K(+)] in bovine urine. PMID- 27394953 TI - Feeding distillers dried grains in replacement of forage in limit-fed dairy heifer rations: Effects on growth performance, rumen fermentation, and total tract digestibility of nutrients. AB - The objective of this study was to determine the effects of increasing dietary concentration of distillers dried grains (DDGS) in dairy heifer rations. A 16-wk randomized complete block design study was conducted using 48 Holstein heifers [199+/-2 d of age; body weight (BW) 206+/-2kg] to evaluate effects of dietary treatment on dry matter (DM) intake, average daily gain, growth performance, rumen fermentation, and nutrient digestibility. Treatments were (1) 30% DDGS with the diet fed at 2.65% of BW, (2) 40% DDGS with the diet fed at 2.50% of BW, and (3) 50% DDGS with the diet fed at 2.35% of BW. The remainder of the diet consisted of grass hay and 1.5% mineral mix. Heifers were individually limit-fed using Calan gates. Heifers were weighed every 2 wk and the ration amount offered was adjusted accordingly. Frame measurements and body condition score were recorded every 2wk. Rumen fluid was collected via esophageal tubing during wk 12 and 16 for pH, ammonia N, and volatile fatty acid analysis. Total-tract digestibility of nutrients was evaluated during wk 16 using fecal grab sampling. No treatment by week interactions were found for any of the growth parameters measured, and growth parameters did not differ among treatments. Heifer DM intake linearly decreased with increasing concentrations of DDGS. Body weight and average daily gain were similar among treatments, whereas gain:feed linearly increased across treatments, with a tendency for a treatment by time interaction. As the dietary concentrations of DDGS increased, rumen ammonia N linearly increased. Acetate proportion and acetate:propionate linearly decreased as DDGS increased, whereas propionate linearly increased. There were treatment by time interactions for propionate proportion and acetate:propionate. Increasing dietary concentrations of DDGS linearly increased total-tract digestibility of DM, organic matter, and crude protein. Limit-feeding diets with greater concentrations of DDGS improved gain:feed and total-tract digestibility of DM and crude protein, and maintained frame growth without increasing body condition score. Results demonstrated that replacing forage with DDGS at up to a 50% inclusion rate in limit-fed rations can maintain heifer growth performance. PMID- 27394954 TI - Identifying risk factors associated with lameness in pasture-based dairy herds. AB - Lameness is a significant welfare concern for dairy farmers and a major contributing economic loss to the dairy industry. Information is limited on environmental and managerial risk factors associated with lameness in Australian dairy herds. The objective of this study was to explore and quantify the environmental and management risk factors associated with lameness in pasture based dairy herds. A cross-sectional study was conducted in 63 pasture-based dairy herds between 2011 and 2014, where all lactating cows were locomotion scored (scale 1-4) during a single visit. Environmental and management variables, such as length of main track and animal handling practices, were recorded during the visit. The prevalence of lameness was measured for each farm and associated risk factors were analyzed using a Generalized Linear Model, where farm was the unit of analysis. Estimated average prevalence of lameness was 18.9% (range 5 to 44.5%). The prevalence of lameness was associated with the amount of rainfall during the 30 d before the farm assessment, smoothness of concrete surface and available space per cow in the holding yard, and length of feed-pad available per cow. Inappropriate handling of cows on the track (e.g., causing sideways pushing among cows) was also a contributing risk factor to high prevalence of lameness in these dairy herds. The findings of this study suggest that by managing several environmental and farming practices, producers can reduce the prevalence of lameness, leading to improved productivity of their herds. PMID- 27394955 TI - Phytoestrogens in milk: Overestimations caused by contamination of the hydrolytic enzyme used during sample extraction. AB - Isoflavones are natural phytoestrogens with antioxidant and endocrine-disrupting potencies. Monitoring of their levels is important to ensure the high quality and safety of food, milk, and dairy products. The efficiency and accuracy of phytoestrogen analyses in complex matrices such as milk depend on the extraction procedure, which often uses hydrolysis by means of the beta glucuronidase/sulfatase enzyme originating from Helix pomatia. The present study reveals that the commercially available hydrolytic enzyme is contaminated by several phytoestrogen isoflavones (genistein, daidzein, formononetin, and biochanin A) and their metabolite equol, as well as flavones (naringenin and apigenin) and coumestrol. We show that the concentrations of daidzein and genistein in the enzyme could have impaired the results of analyses of the main isoflavones in several previously published studies. Of 8 analyzed compounds, only equol was confirmed in the present study and it serves as a reliable marker of phytoestrogens originating from cow feed. Critical reassessment of phytoestrogen concentrations in milk is needed because several previously published studies might have overestimated the concentrations depending on the extraction procedure used. PMID- 27394956 TI - Technical note: Validation of a chemical pregnancy test in dairy cows that uses whole blood, shortened incubation times, and visual readout. AB - Chemical pregnancy testing is an alternative to traditional methods of pregnancy diagnosis (either manual palpation or ultrasound) in postpartum dairy cows and heifers. The objective was to validate a chemical pregnancy test that confers the advantages of using whole blood, rapid incubation times, and visual readout. Blood and milk samples were collected from Holstein dairy cows [n=320; 162+/-62 (mean +/- SD) d in milk] on a confinement farm in northeast Missouri at 28 d after artificial insemination (AI). The samples were assayed for pregnancy associated glycoproteins (PAG) by using a rapid visual test as well as traditional plasma- and milk-based tests. Transrectal ultrasonography diagnosis for pregnancy at 35 to 38 d after AI was the reference (gold) standard for all PAG tests. One hundred fifty-nine cows were diagnosed as pregnant by the reference standard (pregnancies per AI=49.7%). The tests were ELISA and either optical density (OD; measured with a microtiter plate reader; plasma, milk, and rapid visual tests) or visual readout (rapid visual test) were used to diagnose pregnancy. When OD was used, the percentage of pregnant cows classified correctly (sensitivity) for the plasma, milk, and rapid visual tests were 97+/-1, 96+/-2, and 95+/-1% (+/-SE), respectively. The sensitivity of the rapid visual test when assessed visually was 98+/-1%. The specificity (proportion of nonpregnant cows classified correctly) for the plasma, milk, and rapid visual was 94+/-2%, 94+/ 2%, and 93+/-2% when an OD was used. When read visually, the specificity of the rapid visual test was lesser (85+/-3%) because some cows with faint visual signals yielded false positive diagnosis. The overall accuracy (proportion of pregnant and nonpregnant cows diagnosed correctly) was similar for all tests (plasma, milk, rapid visual OD, and rapid visual; 96+/-1, 95+/-1, 94+/-1, and 92+/-2%, respectively). In a second experiment, lactating Holstein cows (n=291) from 4 commercial confinement dairy farms in western Kentucky were tested 25 to 95 d after AI using the rapid visual test. The OD of the rapid visual test followed the known profile for PAG in circulation during the first trimester of pregnancy. The conclusion is that the rapid visual test has equal sensitivity and accuracy as existing PAG tests. A slightly lower specificity was found when the rapid visual test was read visually. PMID- 27394958 TI - Quantitative determination of gracillin by HPLC-MS/MS after oral administration and its application to a pharmacokinetic study. AB - A sensitive and credible high performance liquid chromatography hyphenated to mass spectrometry (HPLC-MS/MS) was established to quantify the concentration of gracillin in rat plasma. The plasma samples were subjected to a direct protein precipitation process with acetonitrile as a precipitant in a single-step. Ginsenoside Rb1 was selected as an internal standard (IS). The chromatographic separation of analyte and IS were carried out on an Inersil ODS-3 C18 column (250*4.6mm, 5MUm) with a binary solvent system containing acetonitrile and 0.1% formic acid in water at a flow rate of 1mLmin(-1) under a gradient elution mode. Mass spectrometric detection was performed on a triple quadrupole tandem mass spectrometer by the multiple reaction monitoring (MRM) mode to examine the precursor-to-daughter ion transitions of 1110.3->948.2 for IS and 886.1->739.9 for gracillin, respectively, in a positive electrospray ionization mode. The calibration curve showed a promising linearity over a concentration range of 0.065-800ngmL(-1) with a better regression coefficient of r(2)=0.9960. The intra- and inter-day precisions (as relative standard deviation) of the assay at three quality control levels were all less than 3.48%, while the intra- and inter-day accuracies (as relative error) ranged from -8.43% to 9.74%, whose data were within the acceptable limits. The mean extraction recoveries of analyte from rat plasma were all more than 74.11%, and no notable matrix effect was observed. Stability experiments revealed that gracillin remained stable throughout the analytical procedure under various stored conditions. The above validated method was successfully used to investigate the pharmacokinetic behaviors of gracillin orally administrated to rats at three proportion doses. The pharmacokinetic analysis would pave the way for understanding the pharmacological actions and provide a meaningful foundation for further development and application in preclinical and clinical use of gracillin in the near future. PMID- 27394957 TI - Monocyte-derived dendritic cells early exposed to Mycobacterium tuberculosis induce an enhanced T helper 17 response and transfer mycobacterial antigens. AB - Tuberculosis (TB) is a complex disease, and the success of the bacterium depends on its ability to evade the immune response. Previously, we determined that Mycobacterium tuberculosis (Mtb) impairs the function of dendritic cells (DC), promoting the generation of cells that are poor stimulators of mycobacterial antigen-specific CD4T cells, which are required to control this persistent infection. In this study, we aimed to determine the mechanisms by which monocyte derived DCs differentiated in the presence of Mtb (MtbDC) may impact on the proliferation of specific anti-mycobacterial T cells. We found that the presence of Mtb during monocyte-derived DC differentiation favours T helper (Th) 2 and Th17 polarization, in detriment of a Th1 response, compared to DC mature with Mtb. The bias on T cell polarization was associated to the profile of C-type lectin receptors expression found in MtbDC (DC-SIGNlow/MRlow/Dectin-1high). Alternatively, MtbDC release Mtb antigens (Ag) that can be taken up and presented by bystander DC, promoting the proliferation of CD4T cells, but to a lesser extent than direct presentation by Mtb-matured DC. In summary, we have further characterized the generation of MtbDC as an effective evasion strategy driven by the pathogen, leading to the inhibition of Ag-presentation and bias of T cell polarization towards Th2 and Th17 profiles, features which partially explain the persistence of Mtb in the host. PMID- 27394959 TI - Nuclear and extranuclear-initiated estrogen receptor signaling crosstalk and endocrine resistance in breast cancer. AB - Estrogens regulate function of reproductive and non-reproductive tissues in healthy and diseased states including breast cancer. They mainly work through estrogen receptor alpha (ERalpha) and/or estrogen receptor beta (ERbeta). There are various ERalpha targeting agents that have been used for treatment of ER (+) breast tumors. The impact of direct nuclear activity of ER is very well characterized in ER (+) breast cancers and development and progression of endocrine resistance. Recent studies also suggested important roles for extranuclear-initiated ERalpha pathways, which would decrease the potency and efficiency of ERalpha targeting agents. In this mini-review, we will discuss the role of nuclear and extra-nuclear ER signaling and how they relate to therapy resistance in breast cancer. PMID- 27394960 TI - Crystal structure of a lithium salt of a glucosyl derivative of lithocholic acid. AB - The crystal structure of a Li(+) salt of a glucosyl derivative of lithocholic acid (lithium 3alpha-(alpha-d-glucopyranosyl)-5beta-cholan-24-oate) has been solved. The crystal belongs to the orthorhombic system, P212121 spatial group, and includes acetone and water in the structure with a 1:1:2 stoichiometry. Monolayers, having a hydrophobic interior and hydrophilic edges, are recognized in the crystal structure. Li(+) is coordinated to three hydroxyl groups of three different glucose residues, with two of them belonging to the same monolayer. A fourth molecule, located in this monolayer, is involved in the coordination of the cation through the carboxylate ion by an electrostatic interaction, thus completing a distorted tetrahedron. All Li(+)-oxygen distances values are very close to the sum of the ionic radius of Li(+) and van der Waals radius of oxygen. Each steroid molecule is linked to other five steroid molecules through hydrogen bonds. Water and acetone are also involved in the hydrogen bond network. A hierarchical organization can be recognized in the crystal, the helical assembly along 21 screw axes being left-handed. PMID- 27394962 TI - Cancer control potential of marine natural product scaffolds through inhibition of tumor cell migration and invasion. AB - The marine environment is a reliable source for the discovery of novel treatment options for numerous diseases. Past research efforts toward the discovery of marine-derived anticancer agents have resulted in several commercially available marine-based drugs. The pharmaceutical value of anticancer drugs from marine natural products (MNPs) ranges from US$563 billion to US$5.69 trillion. In this review, we highlight several marine-derived entities with the potential for cancer control and prevention through the inhibition of crucial tumor cell motility and/or migration steps involved in subsequent cancer metastases. This report also covers the major hurdles typically faced by the MNPs research scientific community. PMID- 27394961 TI - Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress. AB - Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high cholesterol diet for 30days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity. PMID- 27394963 TI - Association of GRIN2B gene polymorphism and Obsessive Compulsive disorder and symptom dimensions: A pilot study. AB - The etiology of OCD is largely unknown, but neuroimaging and pharmacological studies suggest that glutamatergic system plays a significant role on OCD development. We genotyped one polymorphism at GRIN2B (rs1019385) by real time Polymerase Chain Reaction in a sample of Brazilian Obsessive-Compulsive patients and healthy controls, and evaluated its influence on OCD. We found the T-allele and TT genotype to be significantly associated with OCD and ordering dimension. The T-allele was also significantly associated with checking. These preliminary results demonstrated that the GRIN2B gene may confer to some extent the susceptibility to OCD and its symptoms. PMID- 27394964 TI - Phospholipid changes in Rhinella arenarum embryos under different acclimation conditions to copper. PMID- 27394965 TI - The Taming of the TAMs. AB - Tumor-associated macrophages and microglia (TAMs) are considered crucial elements in cancer progression. Recent work reveals the molecular mechanisms underlying acquired resistance to colony-stimulating factor-1 receptor (CSF-1R) inhibitors in glioblastoma (GBM) and shows that targeting TAMs with CSF-1R inhibitors leads to an antitumor response in GBM followed by the acquisition of resistance to treatment through the induction of insulin-like growth factor 1 (IGF-1) expression in TAMs. PMID- 27394966 TI - Mitochondrial UPR: A Double-Edged Sword. AB - The mitochondrial unfolded protein response (UPR(mt)) promotes the recovery of dysfunctional mitochondria. Surprisingly, UPR(mt) activation inadvertently maintains and propagates the deleterious mtDNA in a heteroplasmic Caenorhabditis elegans strain, with detrimental consequences. This study extends our understanding of the UPR(mt) and provides a possible therapeutic target for diseases associated with mtDNA mutations. PMID- 27394967 TI - Changes in integrity of the gill during histidine deficiency or excess due to depression of cellular anti-oxidative ability, induction of apoptosis, inflammation and impair of cell-cell tight junctions related to Nrf2, TOR and NF kappaB signaling in fish. AB - This study firstly explored the possible effects of dietary histidine on structural integrity and the related signaling factor gene expression in the gills of fish. Young grass carp (Ctenopharyngodon idella) were fed with six diets containing gradual levels of histidine for 8 weeks. The results firstly demonstrated that histidine deficiency caused increases in reactive oxygen species (ROS) contents, and severe oxidative damage (lipid peroxidation and protein oxidation) in the gills of fish, which was partially due to the decreased glutathione (GSH) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)]. Further investigations indicated that histidine deficiency caused depressions of those antioxidant enzyme activities are related to the down-regulation of corresponding antioxidant enzyme genes and the related signaling factor Nrf2 mRNA levels. Meanwhile, histidine deficiency induced DNA fragmentation via up-regulation of caspase-3, caspase-8 and caspase-9 expressions that referring to the down-regulation of TOR and S6K mRNA levels. Furthermore, His deficiency down-regulated claudin-b, claudin-c, claudin-3, claudin-12, claudin-15, occludin and ZO-1 transcription in fish gills. These effects were partially related to the up-regulation of pro-inflammatory cytokines, interleukin 1beta (IL-1beta), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and related signaling factor nuclear factor kappaB P65 (NF-kappaB P65) mRNA levels, and the down-regulation of anti-inflammatory cytokines, interleukin 10 (IL-10), transforming growth factor beta1 (TGF-beta1) and related signaling factor IkappaBalpha mRNA levels. Excessive histidine exhibited negative effects that were similar to histidine deficiency, whereas the optimal histidine levels reversed those negative effects. Taken together, our results showed that histidine deficiency or excess impaired the structural integrity of fish gill by disrupted fish antioxidant defenses and regulating the expression of tight junction protein, cytokines, apoptosis, antioxidant enzymes, NF-kappaB p65, IkappaBalpha, TOR, Nrf2, Keap1 and apoptosis-related genes in the fish gills. PMID- 27394968 TI - Effects of dietary oxidized konjac glucomannan sulfates (OKGMS) and acidolysis oxidized konjac glucomannan (A-OKGM) on the immunity and expression of immune related genes of Schizothorax prenanti. AB - In the present study, konjac glucomannan (KGM) was degraded by H2O2, and then used trisulfonated sodium amine and HCl, individually, to obtain two kinds of derivatives: oxidized konjac glucomannan sulfates (OKGMS) and acidolysis-oxidized konjac glucomannan (A-OKGM). The effects of two OKGM modified products on the immune parameters and expressions of toll-like receptor 22 (TLR22), myeloid differentiation factor 88 (MyD88) and interferon regulatory factors 7 (IRF7) genes in Schizothorax prenanti were determined. The alternative haemolytic complement (ACH50) activity was found to be significantly increased by the OKGMS diets. The immunoglobulin M (IgM) level was significantly enhanced by the OKGMS diets. The lysozyme activity was significantly increased by both OKGMS and A-OKGM diets. The superoxide dismutase (T-SOD) activity in fish fed with all doses of OKGMS diets was significantly higher than that in fish fed with basal diet. The glutathione peroxidase (GSH-PX) activity in fish fed with 0.8% and 1.6% A-OKGM diets was significantly higher than control group. The malondialdehyde (MDA) level was significantly decreased by both OKGMS and A-OKGM diets. The 0.8% A-OKGM diet significantly up-regulated TLR22 gene expression in the head kidney and spleen. TLR22 gene expression was significantly promoted by all OKGMS diets in the mesonephros and liver. The MyD88 mRNA level in 1.6% A-OKGM group significantly increased in the head kidney. The low dose of OKGMS significantly induced the MyD88 gene expression in the mesonephros, gut and liver, while 0.8% A OKGM group also showed a significantly enhanced MyD88 mRNA expression in the gut. High dose of OKGMS significantly increased the IRF7 mRNA expression in the mesonephros and spleen. Fish fed with low dose of A-OKGM showed significantly higher expression of IRF7 in the gut and liver. Present study suggested that OKGMS and A-OKGM can act as immunostimulant to improve the immune indexes and up regulate the immune-related gene expressions. PMID- 27394969 TI - Immunity to nervous necrosis virus infections of orange-spotted grouper (Epinephelus coioides) by vaccination with virus-like particles. AB - Nervous necrosis virus (NNV) is a kind of the betanodaviruses, which can cause viral nervous necrosis (VNN) and massive mortality in larval and juvenile stages of orange-spotted grouper (Epinephelus coioides). Due to the lack of viral genomes, virus-like particles (VLPs) are considered as one of the most promising candidates in vaccine study to control this disease. In this study, a type of VLPs, which was engineered on the basis of orange-spotted grouper nervous necrosis virus (OGNNV), was produced from prokaryotes. They possessed the similar structure and size to the native NNV. In addition, synthetic oligodeoxynucleotide (ODN) containing CpG motif was added in vaccines, and the expression patterns of several genes were analyzed after injecting with VLP and VLP with adjuvant (VA) to assess the regulation effect of vaccine for inducing immune responses. RT-PCR assays showed that six related genes in healthy tissues were ubiquitously expressed in all nine tested tissues. The vaccine alone was able to enhance the expression of genes, including MHCIa, MyD88, TLR3, TLR9 and TLR22 after vaccination, indicating that the vaccine was able to induce immune response in grouper. In liver, spleen and kidney, the gene expressions of VA group were all significantly higher than that of VLP group at 72 h post-stimulation, showing that the fish of VA challenge group obtained the longer-lasting protective immunity and resistance to pathogen challenge than that of VLP group. The data indicated that the efficacy of vaccine could be further enhanced by CpG ODN after vaccination and provided the reference for the development of future viral vaccine in grouper. PMID- 27394970 TI - Risk of dementia and death in patients with atrial fibrillation: A competing risk analysis of a population-based cohort. AB - BACKGROUND: Previous studies have stated that atrial fibrillation (AF) is associated with a higher risk of dementia. However, none have examined the competition between death and incident dementia in patients with AF. We evaluated the risk of incident dementia in patients with AF in comparison to people without this arrhythmia, considering of the competing risk of death. METHODS: AF and non AF cohorts were identified using the large administrative database of the Lombardy Region and followed for ten years. Patients with incident dementia were identified if they had an ICD 9 code referring to dementia at hospital discharge or a prescription for any anti-dementia drug. The association of AF with dementia or death was assessed with the multivariable Cox proportional-regression model, sensitivity analysis with a 1:1 propensity score matching and competing-risk analysis. RESULTS: In 2003 a total of 27,431 patients were hospitalized for AF in the Lombardy Region, while the cohort of non-AF counted 1,600,200 people. AF was associated with a higher risk of dementia (17%) and death (51%) at multivariable Cox analysis. These results were confirmed by the model fitted after propensity score matching. However, competing risk analysis found the association between AF and incident dementia was no longer significant (HR 0.99; 95% CI 0.94-1.04). CONCLUSIONS: In this real-world population the association between AF and dementia was no longer statistically significant when death was considered a competing risk. PMID- 27394971 TI - Statins induce regression of carotid artery stenosis: Fact or fiction? PMID- 27394972 TI - Mitochondrial function in heart failure: The impact of ischemic and non-ischemic etiology. AB - BACKGROUND: Although cardiac mitochondrial dysfunction is associated with heart failure (HF), this is a complex syndrome with two predominant etiologies, ischemic HF (iHF) and non-ischemic HF (niHF), and the exact impact of mitochondrial dysfunction in these two distinct forms of HF is unknown. METHODS AND RESULTS: To determine the impact of HF etiology on mitochondrial function, respiration was measured in permeabilized cardiac muscle fibers from patients with iHF (n=17), niHF (n=18), and healthy donor hearts (HdH). Oxidative phosphorylation capacity (OXPHOS), assessed as state 3 respiration, fell progressively from HdH to niHF, to iHF (Complex I+II: 54+/-1; 34+/-4; 27+/ 3pmol.s(-1).mg(-1)) as did citrate synthase activity (CSA: 206+/-18; 129+/-6; 82+/-6nmol.mg(-1).min(-1)). Although still significantly lower than HdH, normalization of OXPHOS by CSA negated the difference in mass specific OXPHOS between iHF and niHF. Interestingly, Complex I state 2 respiration increased progressively from HdH, to niHF, to iHF, whether or not normalized for CSA (0.6+/ 0.2; 1.1+/-0.3; 2.3+/-0.3; pmol.mg(-1).CSA), such that the respiratory control ratio (RCR), fell in the same manner across groups. Finally, both the total free radical levels (60+/-6; 46+/-4AU) and level of mitochondrial derived superoxide (1.0+/-0.2; 0.7+/-0.1AU) were greater in iHF compared to niHF, respectively. CONCLUSIONS: Thus, the HF-related attenuation in OXPHOS actually appears to be independent of etiology when the lower mitochondrial content of iHF is taken into account. However, these findings provide evidence of deleterious intrinsic mitochondrial changes in iHF, compared to niHF, including greater proton leak, attenuated OXPHOS efficiency, and augmented free radical levels. PMID- 27394973 TI - Diastolic dysfunction measured by cardiac magnetic resonance imaging in women with signs and symptoms of ischemia but no obstructive coronary artery disease. AB - BACKGROUND: Women with chest pain and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). The relationship between CMD and diastolic function measured by cardiac magnetic resonance imaging (CMR) is not well described. METHODS: 41 women with suspected CMD underwent CRT and CMR. Left ventricular end-diastolic pressure (LVEDP), coronary flow reserve (CFR) and coronary blood flow (CBF) were measured invasively. Resting CMR of these women and 20 reference controls was assessed for LV mass, septal wall thickness, ejection fraction (LVEF), end-diastolic volume (EDV), peak filling rate (PFR) and time-to-peak-filling rate (tPFR). Pearson correlations and linear regression models were made. RESULTS: Mean age was 55+/-9, all had LVEF>=50%, and 16/41 (40%) had LVEDP>15mmHg. CMD (CFR<2.5 or CBF<50%) was present in 34/41 (83%) women. tPFR (mean 178+/-110ms) and PFR (mean 3.2+/-0.64 EDV/s) were not significantly different in women with or without CMD. tPFR increased with age (r=0.37, p=0.017) and septal wall thickness (r=0.47, p=0.002), while PFR decreased with age (r=-0.45, p=0.003). There was an inverse relationship between CFR and tPFR (r=-0.3, p=0.058). Increasing mass was associated with decreasing CBF (p=0.02). Compared to controls, cases had lower LVEF (p=0.049) and lower EDV (p=0.0002). CONCLUSION: In women with signs and symptoms of ischemia but no obstructive coronary artery disease, CMD and elevated LVEDP are prevalent. While non-endothelial dependent CMD may be related to diastolic dysfunction, further investigation is needed regarding links between CMD, diastolic dysfunction and the development of heart failure with preserved LVEF. PMID- 27394975 TI - Long term survival and prevalence of cardiac allograft vasculopathy in Chinese adults after heart transplantation - A retrospective study in Hong Kong. PMID- 27394974 TI - Findings of an observational investigation of pure remote follow-up of pacemaker patients: is the in-clinic device check still needed? AB - BACKGROUND: Device follow-up is mandatory in the care of patients with a pacemaker. However, in most cases, device checks appear to be mere technical, time-consuming procedures. The aim of this research is to evaluate whether remote follow-up can replace in-clinic device checks by assessing clinical outcomes for pacemaker patients followed only via remote follow-up. METHODS AND RESULTS: Consecutive pacemaker patients followed with remote monitoring were prospectively included by 6 Italian cardiology centers in an observational investigation. The workflow for remote monitoring included an initial assessment by nursing staff and, when necessary, by a responsible physician for medical decisions. No in person visits were scheduled after the start of remote monitoring. One-thousand and two-hundred and fifty one patients (30% female, 75+/-11years old) were followed for a median observation period of 15months. Out of 4965 remote transmissions, 1882 (38%) had at least one clinically relevant event to be investigated further, but, only after 137 transmissions (2.8%), the patients were contacted for an in-clinic visit or hospitalization. Sixty-nine patients died and 124 were hospitalized for various reasons. Atrial fibrillation episodes were the most common clinical events discovered by remote transmissions, occurring in 1339 (26%) transmissions and 471 (38%) patients. CONCLUSIONS: Our experience shows that remote monitoring in a pacemaker population can safely replace in-clinic follow-up, avoiding unnecessary in-hospital device follow-up. PMID- 27394976 TI - Is the last "man" standing in comedy the least funny? A retrospective cohort study of elite stand-up comedians versus other entertainers. AB - BACKGROUND: This study aimed to confirm, in a large, diverse cohort of elite Stand-up Comedians and other entertainers, that there is an inverse association between comedic ability and longevity. METHODS: This retrospective cohort study included 200 Stand-up Comedians (13% women), 113 Comedy Actors (17.5% women), and 184 Dramatic Actors (29.3% women) listed in the top 200 in each category in a popular online ranking website. Longevity within each group was examined adjusting for life expectancy by year of birth and within-group ranking score. RESULTS: Stand-up Comedians were younger than Comedy Actors (median birth year 1962 versus 1947: p<0.001) and Dramatic Actors (1962 versus 1946: p<0.001). Overall, 36/200 (18.0%), 33/114 (29.0%) and 56/184 (30.9%) of Stand-up Comedians, Comedy Actors and Dramatic Actors, respectively, had died (p=0.011). There was a significant gradient (p=0.011) in the age of death, with Stand-up Comedians dying at a younger age (67.1+/-21.3years) than their Comedy Actor (68.9+/-15.4years) and Dramatic Actor (70.7+/-16.6years) counterparts. Stand-up Comedians (38.9% versus 19.6%) were more likely to die prematurely compared to Dramatic Actors; p=0.043, OR 1.98; 95% CI 1.01 to 3.87). Independent of year of birth, for Stand up Comedians alone, higher comedy rank was associated with shorter longevity (hazard ratio 0.938, 95% CI 0.880 to 0.999 for a 10-rank difference; p=0.045). CONCLUSIONS: These data reaffirm an adverse relationship between comedic ability and longevity, with elite Stand-up Comedians more highly rated by the public more likely to die prematurely. PMID- 27394977 TI - Differential thrombotic prolapse burden in either bioresorbable vascular scaffolds or metallic stents implanted during acute myocardial infarction: The snowshoe effect: Insights from the maximal footprint analysis. AB - BACKGROUND: The hypothesized increased thrombus entrapment during bioresorbable vascular scaffold implantation in acute myocardial infarction, the so-called "snowshoe effect" has never been demonstrated. METHODS: Patients enrolled in the BVS STEMI FIRST study matched with STEMI patients implanted with everolimus eluting metal stents (EES) and undergoing optical coherence tomography (OCT) at the index procedure were compared. Quantitative coronary angiography analysis and optical coherence tomography data for evaluation of thrombotic prolapse were reported. Percentage maximal footprint (%MFP) analysis as an indicator of the snowshoe effect was performed. RESULTS: A total of 302 patients were analyzed (151 with BVS and 151 with EES). Of those patients 30 implanted with BVS and 17 implanted with EES were imaged at the index procedure with OCT. Baseline clinical characteristics, TIMI-flow and thrombus burden were similar between groups. Aspiration thrombectomy was similarly performed in the two groups (BVS 83.3% vs 94.1% EES, p=0.405). At the end of the procedure, final TIMI 3 flow was achieved in 93.3% and 82.4% of BVS and EES patients respectively (p=0.296). The %MFP was significantly higher in the BVS treated patients (36.59+/-5.65% vs 17.61+/-4.30, p<0.001). The results of the OCT analysis showed a mean prolapse area (0.61+/ 0.26mm(2) vs 0.90+/-0.31mm(2), p=0.001) and a percentage prolapse area (7.11+/ 2.98mm(2) vs 9.98+/-2.90mm(2), p=0.002) significantly higher in the EES group. CONCLUSIONS: Scaffold structural characteristics such as strut width may play a role in terms of thrombus dislodgment patterns and acute prolapsing material. PMID- 27394978 TI - No benefit of additional treatment with exenatide in patients with an acute myocardial infarction. AB - OBJECTIVES: This double blinded, placebo controlled randomized clinical trial studies the effect of exenatide on myocardial infarct size. The glucagon-like peptide-1 receptor agonist exenatide has possible cardioprotective properties during reperfusion after primary percutaneous coronary intervention for ST segment elevation myocardial infarction. METHODS: 191 patients were randomly assigned to intravenous exenatide or placebo initiated prior to percutaneous coronary intervention using 10MUg/h for 30min followed by 0.84MUg/h for 72h. Patients with a previous myocardial infarction, Trombolysis in Myocardial Infarction flow 2 or 3, multi-vessel disease, or diabetes were excluded. Magnetic resonance imaging (MRI) was performed to determine infarct size, area at risk (AAR) (using T2-weighted hyperintensity (T2W) and late enhancement endocardial surface area (ESA)). The primary endpoint was of 4-month final infarct size, corrected for the AAR measured in the acute phase using MRI. RESULTS: After exclusion, 91 patients (age 57.4+/-10.1years, 76% male) completed the protocol. There were no baseline differences between groups. No difference was found in infarct size corrected for the AAR in the exenatide group compared to the placebo group (37.1+/-18.8 vs. 39.3+/-20.1%, p=0.662). There was also no difference in infarct size (18.8+/-13.2 vs. 18.8+/-11.3% of left ventricular mass, p=0.965). No major adverse cardiac events occurred during the in-hospital phase. CONCLUSION: Exenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention. PMID- 27394979 TI - Novel risk factors for acute coronary syndromes and emerging therapies. AB - Acute coronary syndromes represent not merely disrupted atherosclerotic plaques or luminal stenoses but rather a complex clinical syndrome. The traditional conception of pathogenesis and management of ACS has been challenged by numerous recent landmark ACS trials. Current prognostication models lack clinical precision and can be challenging to the clinicians in tailoring management strategies for individual patients. In this review we summarise the emerging evidence of novel risk factors (plaque phenotype, coronary blood flow, endothelial dysfunction, microvascular dysfunction, and inflammation) in predicting future events and outcomes in ACS population. As the search for miracle cure for ischaemic heart disease continues, one is hopeful that emerging therapeutic approaches targeting these novel risk factors will improve long-term outcomes of ACS. PMID- 27394980 TI - Left ventricular noncompaction mimicking hypertrophic obstructive cardiomyopathy. PMID- 27394981 TI - Apical aneurysm, apical thrombus, ventricular tachycardia and cerebral hemorrhagic infarction in a patient of mid-ventricular non-obstructive hypertrophic cardiomyopathy: A case report. PMID- 27394982 TI - Submitral aneurysm and the new imaging modalities: Will magnetic resonance imaging be necessary? AB - Submitral aneurysm is a rare cardiac malformation commonly reported in young adult African ancestry. Transthoracic echocardiogram is a gold standard test for diagnosis. Magnetic resonance imaging provides detailed anatomic and functional information of the heart. We present a case of a large bilobed submitral aneurysm in-witch the magnetic resonance imaging confirmed the same findings of the transthoracic echocardiography and in addiction also showed a parietal thrombus. PMID- 27394983 TI - Myocardial bridging and ecstasy: A fatal combination involving a 22year-old male. PMID- 27394984 TI - The dawn of a new era in onco-cardiology: The Kumamoto Classification. AB - The term "onco-cardiology" has been used in reference to cardiotoxicity in the treatment of malignant disease. In actual clinical situations, however, cardiovascular disease (CVD) associated with malignant disease and the concurrence of atherosclerotic disease with malignant disease are commonly observed, complicating the course of treatment. Patients with malignant disease associated with coronary artery disease often die from the cardiovascular disease, so it is essential to classify these disease states. Additionally, the prevalence of these classifications makes it easy to manage patients with malignant disease and coronary artery disease. We divided the broad field of onco cardiology into 4 classifications based on clinical scenarios (CSs): CS1 represents the so-called paraneoplastic syndrome. CS2 represents cardiotoxicity during treatment of malignant diseases. CS3 represents the concurrence of atherosclerotic disease with malignant disease, and CS4 represents cardiovascular disease with benign tumors. This classification facilitates the management of patients with malignant disease and coronary artery disease by promoting not only the primary but also the secondary prevention of CVD. PMID- 27394985 TI - Relationship between employment and mental health outcomes following Cardiac Rehabilitation: an observational analysis from the National Audit of Cardiac Rehabilitation. AB - BACKGROUND: Employment status has been shown to impact mental health state and intervention outcomes, yet still to be studied in a Cardiac Rehabilitation (CR) population. This observational study investigated the relationship between employment status and mental health outcomes following Cardiac Rehabilitation (CR). METHODS: All patients with an eligible cardiovascular incident entered into the National Audit of Cardiac Rehabilitation (NACR) 1 January 2013-31st December 2015. Logistic regression comparing the association between employment status and normal mental health categories. RESULTS: A total of 24,242 CR patients with completed post CR assessments were included and had representative age and gender distribution (mean 65years, 73.2% male). At baseline the unemployed status had a lower proportion of patients in normal healthy categories than other groups (T test and chi-squared p=<0.05). The regression analyses revealed no significant association between retired and employed groups and outcome. There was significant association between unemployed patients and all mental health outcomes except anxiety; all p values<0.05 and odds ratios between 0.525 and 0.772 showing less likelihood of achieving the normal healthy category. CONCLUSIONS: This is the first UK study, using routinely collected data, to investigate in coronary heart disease patients the impact of employment status on outcomes. The findings were that when weighted for baseline differences, unemployed patients mostly had poorer outcomes. Teams involved in CR delivery should take particular care when interpreting mental health baseline measures when setting CR goals, especially in relation to unemployed patients, and efforts should be made in providing more patient tailored interventions. PMID- 27394986 TI - Protective effect of gentiopicroside against dextran sodium sulfate induced colitis in mice. AB - This study was designed to investigate the anti-inflammatory activity of the pure compound gentiopicroside (Gent) on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to explore the possible related mechanisms. Experimental colitis was induced in ICR mice by dissolving 5% DSS in their drinking water for 7days. Gent (200, 100, and 50mg/kg) and 5-aminosalicylic acid (5-ASA, 100mg/kg) were oral administrated once a day for 7days. Anti-inflammatory effects were evaluated by comparing extend of colonic mucosal injury assessed by disease activity index (DAI), colon length, histopathological examination, and biochemical test. The possible mechanisms of Gent activities were explored by evaluating expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 using real-time fluorogenic PCR and expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) using Western blotting. The results showed that oral administration of Gent significantly attenuated DSS-induced loss of body weight, diarrhea, shortening of colon length and histological changes, associated with the decrease in the activity of myeloperoxidase (MPO) in the colon. In addition, the mRNA expression of TNF-alpha, IL-1beta, IL-6 and the overexpression of COX-2 and iNOS proteins in the colon were down-regulated by Gent treatment. To our knowledge, this is the first study to demonstrate that Gent treatment can exert anti-inflammatory effects on experimental acute colitis through attenuating the expression levels of TNF-alpha, IL-1beta, IL-6, iNOS and COX-2, and it may present the therapeutic potential in the treatment of colitis. PMID- 27394987 TI - Genomic and metagenomic challenges and opportunities for bioleaching: a mini review. AB - High-throughput genomic technologies are accelerating progress in understanding the diversity of microbial life in many environments. Here we highlight advances in genomics and metagenomics of microorganisms from bioleaching heaps and related acidic mining environments. Bioleaching heaps used for copper recovery provide significant opportunities to study the processes and mechanisms underlying microbial successions and the influence of community composition on ecosystem functioning. Obtaining quantitative and process-level knowledge of these dynamics is pivotal for understanding how microorganisms contribute to the solubilization of copper for industrial recovery. Advances in DNA sequencing technology provide unprecedented opportunities to obtain information about the genomes of bioleaching microorganisms, allowing predictive models of metabolic potential and ecosystem-level interactions to be constructed. These approaches are enabling predictive phenotyping of organisms many of which are recalcitrant to genetic approaches or are unculturable. This mini-review describes current bioleaching genomic and metagenomic projects and addresses the use of genome information to: (i) build metabolic models; (ii) predict microbial interactions; (iii) estimate genetic diversity; and (iv) study microbial evolution. Key challenges and perspectives of bioleaching genomics/metagenomics are addressed. PMID- 27394988 TI - Phenotype microarray analysis may unravel genetic determinants of the stress response by Rhodococcus aetherivorans BCP1 and Rhodococcus opacus R7. AB - In the present study, the response of Rhodococcus aetherivorans BCP1 and Rhodococcus opacus R7 to various stress conditions and several antimicrobials was examined by PM in relation with genetic determinants, as revealed by annotation analysis of the two genomes. Comparison between metabolic activities and genetic features of BCP1 and R7 provided new insight into the environmental persistence of these two members of the genus Rhodococcus. PMID- 27394989 TI - Comparative proteomic analysis of sulfur-oxidizing Acidithiobacillus ferrooxidans CCM 4253 cultures having lost the ability to couple anaerobic elemental sulfur oxidation with ferric iron reduction. AB - In extremely acidic environments, ferric iron can be a thermodynamically favorable electron acceptor during elemental sulfur oxidation by some Acidithiobacillus spp. under anoxic conditions. Quantitative 2D-PAGE proteomic analysis of a resting cell suspension of a sulfur-grown Acidithiobacillus ferrooxidans CCM 4253 subculture that had lost its iron-reducing activity revealed 147 protein spots that were downregulated relative to an iron-reducing resting cell suspension of the antecedent sulfur-oxidizing culture and 111 that were upregulated. Tandem mass spectrometric analysis of strongly downregulated spots identified several physiologically important proteins that apparently play roles in ferrous iron oxidation, including the outer membrane cytochrome Cyc2 and rusticyanin. Other strongly repressed proteins were associated with sulfur metabolism, including heterodisulfide reductase, thiosulfate:quinone oxidoreductase and sulfide:quinone reductase. Transcript-level analyses revealed additional downregulation of other respiratory genes. Components of the iron oxidizing system thus apparently play central roles in anaerobic sulfur oxidation coupled with ferric iron reduction in the studied microbial strain. PMID- 27394990 TI - Water resource recovery by means of microalgae cultivation in outdoor photobioreactors using the effluent from an anaerobic membrane bioreactor fed with pre-treated sewage. AB - With the aim of assessing the potential of microalgae cultivation for water resource recovery (WRR), the performance of three 0.55m(3) flat-plate photobioreactors (PBRs) was evaluated in terms of nutrient removal rate (NRR) and biomass production. The PBRs were operated outdoor (at ambient temperature and light intensity) using as growth media the nutrient-rich effluent from an AnMBR fed with pre-treated sewage. Solar irradiance was the most determining factor affecting NRR. Biomass productivity was significantly affected by temperatures below 20 degrees C. The maximum biomass productivity (52.3mgVSS.L(-1).d(-1)) and NRR (5.84mgNH4-N.L(-1).d(-1) and 0.85mgPO4-P.L(-1).d(-1)) were achieved at solar irradiance of 395MUE.m(-2).s(-1), temperature of 25.5 degrees C, and HRT of 8days. Under these conditions, it was possible to comply with effluent nutrient standards (European Directive 91/271/CEE) when the nutrient content in the influent was in the range of 40-50mgN.L(-1) and 6-7mg P.L(-1). PMID- 27394991 TI - Alleviation of harmful effect in stillage reflux in food waste ethanol fermentation based on metabolic and side-product accumulation regulation. AB - Stillage reflux fermentation in food waste ethanol fermentation could reduce sewage discharge but exert a harmful effect because of side-product accumulation. In this study, regulation methods based on metabolic regulation and side-product alleviation were conducted. Result demonstrated that controlling the proper oxidation-reduction potential value (-150mV to -250mV) could reduce the harmful effect, improve ethanol yield by 21%, and reduce fermentation time by 20%. The methods of adding calcium carbonate to adjust the accumulated lactic acid showed that ethanol yield increased by 17.3%, and fermentation time decreased by 20%. The accumulated glyceal also shows that these two methods can reduce the harmful effect. Fermentation time lasted for seven times without effect, and metabolic regulation had a better effect than side-product regulation. PMID- 27394992 TI - Aerobic granulation of protein-rich granules from nitrogen-lean wastewaters. AB - Proteins (PN)-rich granules are stable in structure in long-term reactor operations. This study proposed to cultivate PN-rich granules with PN/polysaccharides (PS) >20 from nitrogen lean wastewater, with ammonia-nitrogen as sole nitrogen source at chemical oxygen demand (COD)/N of 153.8. The yielded granules can sustain their structural stability in sequencing batch reactor mode for sufficient treatment of wastewaters up to 7000mg/L COD and with COD/N<500 and in continuous-flow reactor for successful 216-d treatment of wastewaters up to organic loading rate (OLR) of 39kg/m(3)-d. The produced granules were enriched with Firmicutes and beta-proteobacteria as dominating strains. More than 58% of the nitrogen fed in the nitrogen-lean wastewater is converted to the PN in the granules. The replacement of ammonia by nitrate as sole nitrogen source led to granules enriched with gamma-proteobacteria which are easily deteriorated at low OLR. PMID- 27394993 TI - Performance of anaerobic membrane bioreactor during digestion and thickening of aerobic membrane bioreactor excess sludge. AB - In this study, we evaluated the performance of an anaerobic membrane bioreactor in terms of digestion and thickening of excess sludge from an aerobic membrane bioreactor. A digestion reactor equipped with an external polytetrafluoroethylene tubular microfiltration membrane module was operated in semi-batch mode. Solids were concentrated by repeated membrane filtration and sludge feeding, and their concentration reached 25,400mg/L after 92d. A high chemical oxygen demand (COD) removal efficiency, i.e., 98%, was achieved during operation. A hydraulic retention time of 34d and a pulse organic loading rate of 2200mg-COD/(L-reactor) gave a biogas production rate and biogas yield of 1.33L/(reactor d) and 0.08L/g CODinput, respectively. The external membrane unit worked well without membrane cleaning for 90d. The transmembrane pressure reached 25kPa and the filtration flux decreased by 80% because of membrane fouling after operation for 90d. PMID- 27394994 TI - Screening of freshwater and seawater microalgae strains in fully controlled photobioreactors for biodiesel production. AB - Strain selection is one of the primary hurdles facing cost-effective microalgal biodiesel production. Indeed, the strain used affects both upstream and downstream biodiesel production processes. This study presents a screening procedure that considers the most significant criteria in microalgal biodiesel production including TAG production and wet extraction and recovery of TAGs. Fourteen freshwater and seawater strains were investigated. Large variation was observed between the strains in all the screening criteria. The overall screening procedure ultimately led to the identification of Parachlorella kessleri UTEX2229 and Nannochloropsis gaditana CCMP527 as the best freshwater and seawater strains, respectively. They featured the largest areal TAG productivity equal to 2.7*10( 3) and 2.3*10(-3)kgm(-2)d(-1), respectively. These two strains also displayed encouraging cell fragility in a high pressure bead milling process with 69% and 98% cell disruption at 1750bar making them remarkable strains for TAG extraction in wet environment. PMID- 27394996 TI - A one-stage cultivation process for lipid- and carbohydrate-rich biomass of Scenedesmus obtusiusculus based on artificial and natural water sources. AB - A one-stage cultivation process of the microalgae Scenedesmus obtusiusculus with medium based on natural water sources was developed to enhance lipids and carbohydrates. A medium based on artificial sea water, Baltic Sea water and river water with optimized nutrient concentrations compared to the standard BG-11 for nitrate (-75%), phosphate and iron (-90%) was used for cultivation. Although nitrate exhaustion over cultivation resulted in nitrate limitation, growth of the microalgae was not reduced. The lipid content increased from 6.0% to 19.9%, an increase in oleic and stearic acid was observed. The unsaponifiable matter of the lipid fraction was reduced from 19.5% to 11.4%. The carbohydrate yield rose from 45% to 50% and the protein content decreased from 32.4% to 15.9%. Using natural water sources with optimized nutrient concentrations could open the opportunity to modulate biomass composition and to reduce the cultivation costs. PMID- 27394995 TI - Improving succinic acid production by Actinobacillus succinogenes from raw industrial carob pods. AB - Carob pods are an inexpensive by-product of locust bean gum industry that can be used as renewable feedstock for bio-based succinic acid. Here, for the first time, unprocessed raw carob pods were used to extract a highly enriched sugar solution, afterwards used as substrate to produce succinic acid using Actinobacillus succinogenes. Batch fermentations containing 30g/L sugars resulted in a production rate of 1.67gSA/L.h and a yield of 0.39gSA/g sugars. Taking advantage of A. succinogenes' metabolism, uncoupling cell growth from succinic acid production, a fed-batch mode was implemented to increase succinic acid yield and reduce by-products formation. This strategy resulted in a succinic acid yield of 0.94gSA/g sugars, the highest yield reported in the literature for fed-batch and continuous experiments, while maintaining by-products at residual values. Results demonstrate that raw carob pods are a highly efficient feedstock for bio based succinic acid production. PMID- 27394997 TI - Enhancement of anaerobic methanogenesis at a short hydraulic retention time via bioelectrochemical enrichment of hydrogenotrophic methanogens. AB - Anaerobic digestion (AD) is an important energy strategy for converting organic waste to CH4. A major factor limiting the practical applicability of AD is the relatively long hydraulic retention time (HRT) which declines the treatment efficiency of digesters. A coupling process of anaerobic digestion and 'electromethanogenesis' was proposed to enhance anaerobic digestion at a short HRT in this study. Microorganisms analysis indicated that the electric-biological reactor enriched hydrogenotrophic methanogens in both cathodic biofilm and suspended sludge, helping achieve the high organic removal (71.0% vs 42.3% [control reactor]) and CH4 production (248.5mL/h vs 51.3mL/h), while the additional electric input was only accounted for 25.6% of the energy income from the increased CH4 production. This study demonstrated that a bioelectrochemical enhanced anaerobic reactor could improve the CH4 production and organic removal at a short HRT, providing an economically feasible scheme to treat wastewater. PMID- 27394998 TI - Maximising biohydrogen yields via continuous electrochemical hydrogen removal and carbon dioxide scrubbing. AB - The use of electrochemical hydrogen removal (EHR) together with carbon dioxide removal (CDR) was demonstrated for the first time using a continuous hydrogen producing fermenter. CDR alone was found to increase hydrogen yields from 0.07molH2molhexose to 0.72molH2molhexose. When CDR was combined with EHR, hydrogen yields increased further to 1.79molH2molhexose. The pattern of carbohydrate utilisation and volatile fatty acid (VFA) production are consistent with the hypothesis that increased yields are the result of relieving end product inhibition and inhibition of microbial hydrogen consumption. In situ removal of hydrogen and carbon dioxide as demonstrated here not only increase hydrogen yield but also produces a relatively pure product gas and unlike other approaches can be used to enhance conventional, mesophilic, CSTR type fermentation of low grade/high solids biomass. PMID- 27394999 TI - Acidification of prehydrolysis liquor and spent liquor of neutral sulfite semichemical pulping process. AB - Acidification has been commercialized for producing kraft lignin from black liquor of kraft pulping process. This work intended to evaluate the effectiveness of acidification in extracting lignocelluloses from the spent liquor of neutral sulfite semichemical pulping (NSSC) process and from prehydrolysis liquor (PHL) of kraft-based dissolving pulp production process. The results showed that the NSSC and PHL spent liquors had some lignin-carbohydrate complexes (LCC), and that the square weighted counts of particles with a chord length of 50-150MUm in the spent liquors were significantly increased as pH dropped to 1.5. Interestingly, the acidification reduced the lignosulfonate/lignin content of NSSC and PHL by 13% or 20%, while dropped their oligosugars content by 75% and 38%, respectively. On a dry basis, the precipitates had more carbon, hydrogen and a high heating value of 18-22MJ/kg, but less oxygen, than spent liquors. The precipitates of PHL could be used as fuel. PMID- 27395000 TI - Enhanced dewatering of excess activated sludge through decomposing its extracellular polymeric substances by a Fe@Fe2O3-based composite conditioner. AB - Efficient sludge dewatering methods are highly desired by municipal wastewater treatment plants. In this study, Fe@Fe2O3 nanomaterial, combined with polydiallyldimethylammonium chloride (PDMDAAC) and H2SO4, was used for sludge dewatering. This composite conditioner exhibited an excellent dewatering capability. By using uniform design, the optimized dosages of Fe@Fe2O3, H2SO4 and PDMDAAC were determined to be 40, 136 and 4.8mg/gDS (dry solids), respectively. The moisture content of sludge cake decreased from 78.1% to 64.8%, and the capillary suction time from 56 to 21s. The sludge extracellular polymeric substances (EPS) were decomposed, resulting in greater conversion of the bound water into free water and the release of free water. The electron spin resonance results show that the molecular oxygen activation process induced by Fe@Fe2O3 produced hydroxyl radicals, which were mainly responsible for the EPS decomposition. In this way, an efficient composite conditioner for enhancing sludge dewatering was developed. PMID- 27395001 TI - Long-term dinoflagellate culture performance in a commercial photobioreactor: Amphidinium carterae case. AB - The aim of this work was to study the culture performance of a dinoflagellate in a commercial photobioreactor. The results obtained during this long-term experiment allow to confirm that Amphidinium carterae is a promising dinoflagellate that can be exploited successfully in closed systems, in semi continuous mode in indoor and outdoor environments. The average results in an indoor 5cm light-path 320L photobioreactor were, in terms of specific growth rate (0.29d(-1)), duplication time (3.1d(-1)) and dry biomass productivity (78mgL( 1)d(-1)). Specific compounds production was found including omega3 and omega6 fatty acids and, pigments (Peridinin, beta-carotene). These promising results, besides unique characteristics found during the exploitation period such as resistance to mechanical stress, self-control of contaminant organisms, and quick cells aggregation when the culture is not in turbulence conditions, makes A. carterae one of the new target species suitable for commercially exploitation on an industrial scale. PMID- 27395002 TI - Effect of self-purging pyrolysis on yield of biochar from maize cobs, husks and leaves. AB - In this study, biochar was produced from maize residues (cobs, husks, leaves) in a lab-scale pyrolysis reactor without using a purging gas. The physicochemical properties of biomass and biochar were analysed. Box-Behnken design was used to optimise operational conditions for biochar yields. Multivariate correlations of biochar yields were established using reduced quadratic models with R(2)=0.9949, 0.9801 and 0.9876 for cobs, husks and leaves, respectively. Biochar yields were negatively correlated with the temperature, which was significantly influenced by the exothermic reactions during the pyrolysis of maize residues. The heating rate was found to have the least effect on biochar yields. Under optimal conditions, the maximum biochar yields from cobs, husks and leaves were 33.42, 30.69 and 37.91%, respectively. The highest biochar yield from maize leaves was obtained at a temperature of 300 degrees C, a heating rate of 15 degrees C/min and a holding time of 30min. PMID- 27395003 TI - Effect of external magnetic field on the Kbeta/Kalpha X-ray intensity ratios of TixNi1-x alloys excited by 59.54 and 22.69keV photons. AB - The effects of external magnetic field and exciting photon energies on the Kbeta/Kalpha X-ray intensity ratios of various alloy compositions of Ti-Ni transition metal alloys have been investigated in this work using X-ray fluorescence spectroscopy. The spectrum of characteristic K-X-ray photons from pure Ti, pure Ni and TixNi1-x (x=0.30; 0.40; 0.50; 0.60; 0.70) alloys were detected with a high resolution Si (Li) solid-state detector. Firstly, Kbeta/Kalpha X-ray intensity ratios of pure Ti, pure Ni and TixNi1-x alloys were measured following excitation by 59.54keV gamma-rays from a 200mCi (241)Am radioactive point source without any magnetic field and under 0.5 and 1T external magnetic fields, separately. Later, the same measurements were repeated under the same experimental conditions for 22.69keV X-rays from a 370 MBq(1)(0)(9)Cd radioactive point source. The results obtained for Kbeta/Kalpha X-ray intensity ratios of pure Ti, pure Ni, Ti and Ni in various Ti-Ni alloys were evaluated in terms of both external magnetic field effect and exciting photon energy effect. When the results obtained for both exciting photon energies are evaluated in terms of changing of Kbeta/Kalpha X-ray intensity ratios depending on the alloy composition, the tendency of these changes are observed to be similar. Also, Kbeta/Kalpha X-ray intensity ratios for all samples examined have changed with increasing external magnetic field. Therefore, the results obtained have shown that Kbeta/Kalpha X-ray intensity ratios of Ti and Ni in TixNi1-x alloys are connected with the external magnetic field. The present study makes it possible to perform reliable interpretation of experimental Kbeta/Kalpha X-ray intensity ratios for Ti, Ni and TixNi1-x alloys and can also provide quantitative information about the changes of the Kbeta/Kalpha X-ray intensity ratios of these metals with alloy composition. PMID- 27395004 TI - Elevated soluble IL-7 receptor concentration in non-survivor ICU patients. PMID- 27395005 TI - Chronic healthcare expenditure in survivors of sepsis in the intensive care unit. PMID- 27395006 TI - The atypical cadherin Celsr1 functions non-cell autonomously to block rostral migration of facial branchiomotor neurons in mice. AB - The caudal migration of facial branchiomotor (FBM) neurons from rhombomere (r) 4 to r6 in the hindbrain is an excellent model to study neuronal migration mechanisms. Although several Wnt/Planar Cell Polarity (PCP) components are required for FBM neuron migration, only Celsr1, an atypical cadherin, regulates the direction of migration in mice. In Celsr1 mutants, a subset of FBM neurons migrates rostrally instead of caudally. Interestingly, Celsr1 is not expressed in the migrating FBM neurons, but rather in the adjacent floor plate and adjoining ventricular zone. To evaluate the contribution of different expression domains to neuronal migration, we conditionally inactivated Celsr1 in specific cell types. Intriguingly, inactivation of Celsr1 in the ventricular zone of r3-r5, but not in the floor plate, leads to rostral migration of FBM neurons, greatly resembling the migration defect of Celsr1 mutants. Dye fill experiments indicate that the rostrally-migrated FBM neurons in Celsr1 mutants originate from the anterior margin of r4. These data suggest strongly that Celsr1 ensures that FBM neurons migrate caudally by suppressing molecular cues in the rostral hindbrain that can attract FBM neurons. PMID- 27395007 TI - A novel ciliopathic skull defect arising from excess neural crest. AB - The skull is essential for protecting the brain from damage, and birth defects involving disorganization of skull bones are common. However, the developmental trajectories and molecular etiologies by which many craniofacial phenotypes arise remain poorly understood. Here, we report a novel skull defect in ciliopathic Fuz mutant mice in which only a single bone pair encases the forebrain, instead of the usual paired frontal and parietal bones. Through genetic lineage analysis, we show that this defect stems from a massive expansion of the neural crest-derived frontal bone. This expansion occurs at the expense of the mesodermally-derived parietal bones, which are either severely reduced or absent. A similar, though less severe, phenotype was observed in Gli3 mutant mice, consistent with a role for Gli3 in cilia-mediated signaling. Excess crest has also been shown to drive defective palate morphogenesis in ciliopathic mice, and that defect is ameliorated by reduction of Fgf8 gene dosage. Strikingly, skull defects in Fuz mutant mice are also rescued by loss of one allele of fgf8, suggesting a potential route to therapy. In sum, this work is significant for revealing a novel skull defect with a previously un-described developmental etiology and for suggesting a common developmental origin for skull and palate defects in ciliopathies. PMID- 27395008 TI - Towards elucidation of the toxic mechanism of copper on the model green alga Chlamydomonas reinhardtii. AB - Toxic effects of copper on aquatic organisms in polluted water bodies have garnered particular attention in recent years. Microalgae play an important role in aquatic ecosystems, and they are sensitive to heavy metal pollution. Thus, it is important to clarify the mechanism of copper toxicity first for ecotoxicology studies. In this study, the physiological, biochemical and gene expression characteristics of a model green microalga, Chlamydomonas reinhardtii, with 0, 50, 150 and 250 MUM copper treatments were investigated. The response of C. reinhardtii to copper stress was significantly shown at a dose dependent manner. Inhibition of cell growth and variation of total chlorophyll content were observed with copper treatments. The maximum photochemical efficiency of PSII, actual photochemical efficiency of PSII and photochemical quenching value decreased in the 250 MUM copper treatment with minimum values equal to 28, 24 and 60 % of the control values respectively. The content of lipid peroxidation biomarker malondialdehyde with copper treatments increased with a maximum value sevenfold higher than the control value. Inhibition of cell growth and photosynthesis was ascribed to peroxidation of membrane lipids. The glutathione content and activities of antioxidant enzymes, glutathione S-transferase, glutathione peroxidase, superoxide dismutase and peroxidase were induced by copper. Interestingly, the expression of antioxidant genes and the photosynthetic gene decreased in most copper treatments. In conclusion, oxidative stress caused by production of excess reactive oxidative species might be the major mechanism of copper toxicity on C. reinhardtii. PMID- 27395009 TI - Methodology for determining material constants of anisotropic materials belonging to the transversely isotropic system by ultrasound method. AB - The paper presents the methodology and results of the ultrasound determination of material constants of anisotropic materials belonging to the transversely isotropic system. Ultrasound through-transmission method was used for determining material constants. Based on the measurements of velocities of longitudinal and transverse ultrasounds waves propagation, respectively polarized in required directions all the elastic and the material constant of the test materials were determined. Measurements of all the velocities necessary to determine the elastic constants were performed on a specially prepared individual samples. The tests were carried out on porous polycrystalline anisotropic graphites of anisotropy in Young's modulus of up to 26% and Al2O3 composites with up to 30% of hBN causing anisotropy of Young's modulus of up to 50%. It was found that for all tested samples the value of Young's modules and modules stiffness decreasing with increasing porosity in the graphites and increasing content of hBN in Al2O3. PMID- 27395010 TI - Response to: "Letter to the Editor: Trocar Site Hernia Prevention in Laparoscopic Bariatric Surgery". PMID- 27395011 TI - Risk of prescribing errors in acutely admitted patients: a pilot study. AB - Background Prescribing errors in emergency settings occur frequently. Knowing which patients have the highest risk of errors could improve patient outcomes. Objective The aim of this study was to test an algorithm designed to assess prescribing error risk in individual patients, and to test the feasibility of medication reviews in high-risk patients. Setting The study was performed at the Acute Admissions Unit at Aarhus University Hospital, Denmark. Methods The study was an interventional pilot study. Patients included were assessed according to risk of prescribing errors with the aid of an algorithm called 'Medication Risk Score' (MERIS). Based on the score, high-risk patients were offered a medication review. The clinical relevance of the medication reviews was assessed retrospectively. Main outcome measure The number and nature of prescribing errors during the patients' hospitalisation. Results The study included 103 patients, all of whom could be risk assessed with the algorithm MERIS. MERIS stratified 38 patients as high-risk patients and 65 as low-risk patients. The 103 patients were prescribed a total of 848 drugs in which 88 prescribing errors were found (10.4 %). Sixty-two of these were found in patients in the high-risk group. In general, the medication reviews were found to be clinically relevant and approximately 50 % of recommendations were implemented. Conclusion MERIS was found to be applicable in a clinical setting and stratified most patients with prescribing errors into the high-risk group. The medication reviews were feasible and found to be clinically relevant by most raters. PMID- 27395012 TI - Bridging the gap: improving safe prescribing from university to workplace. AB - One of the challenges for Foundation Year 1 junior doctors is to apply the theoretical pharmacology from their undergraduate years into practical prescribing. The EQUIP study in 2009 investigated the causes of prescribing errors by junior doctors. Respondents in the study reported deficiencies in their education for prescribing skills and error prevention. The study suggested more could be done during undergraduate education to link theory with practice. This article describes an initiative from a hospital clinical pharmacy team to address this gap in contextual prescribing skills. Final year medical students (FY0s) were allocated to the Belfast Trust for an 11 week placement. The Clinical Pharmacy team developed a 3 h FY0 workshop focusing on practical prescribing scenarios identified as high risk by local medicines safety teams. The workshops included simulated case studies requiring the FY0 student to discuss medicine use with patients, prescribe admission drug charts and use local guidelines to safely prescribe high risk medicines. Each student was assessed using direct observation of procedural skills (DOPS). Feedback was overwhelmingly positive. Students appreciated the practical elements of the workshop. Initially there was an over reliance on written medication history without verbally engaging the patient. Following pharmacist feedback before the DOPS students demonstrated a clear improvement in patient communication. Feedback from the FY0 students also identified additional learning needs that formed the basis of further teaching. PMID- 27395013 TI - Functional imaging in liver tumours. AB - Functional imaging encompasses techniques capable of assessing physiological parameters of tissues, and offers useful clinical information in addition to that obtained from morphological imaging. Such techniques may include magnetic resonance imaging with diffusion-weighted sequences or hepatobiliary contrast agents, perfusion imaging, or molecular imaging with radiolabelled tracers. The liver is of major importance in oncological practice; not only is hepatocellular carcinoma one of the malignancies with steadily rising incidence worldwide, but hepatic metastases are regularly observed with a range of solid neoplasms. Within the realm of hepatic oncology, different functional imaging modalities may occupy pivotal roles in lesion characterisation, treatment selection and follow-up, depending on tumour size and type. In this review, we characterise the major forms of functional imaging, discuss their current application to the management of patients with common primary and secondary liver tumours, and anticipate future developments within this field. PMID- 27395014 TI - Routine extra-hepatic bile duct resection in gallbladder cancer patients without bile duct infiltration: A systematic review. AB - AIM: The optimal treatment for advanced gallbladder cancer, in particular T2 stage cancer, is unclear. The use of "radical cholecystectomy" or more extended procedures with extra-hepatic bile duct resection are matter of debate. Due to the lack of consensus regarding the oncological significance of routine extra hepatic bile duct (EBD) resection for gallbladder carcinoma, we decided to perform a systematic review investigating the real benefit of this procedure focusing on the primary outcomes of overall survival and disease-free survival. METHODS: A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central according to the PRISMA statement guidelines for conducting and reporting systematic reviews. Multiple primary and secondary outcomes were analyzed. RESULTS: The selected articles included 424 patients who underwent routine EBD resection without bile duct infiltration. Only two papers discussed the number of dissected lymph nodes during EBD resection for gallbladder carcinoma. Four of the seven included papers reported on tumor involvement in lymph nodes at rates ranging between 39% and 83%. All of the studies included in this systematic review reported on results of overall survival. In general, 5-years OS rate of the EBD-resected patients was not significantly different than that of the EBD-preservation group, while the mobility was significantly higher in the EBD resection group. CONCLUSIONS: Routine EBD resection in gallbladder cancer patients without bile duct infiltration is not associated with improved overall survival, improved lymph node harvesting or with minor recurrence rate, but it is associated with higher morbidity rates. PMID- 27395015 TI - Comparison of water-energy trajectories of two major regions experiencing water shortage. AB - Water shortage, increased demand and rising energy costs are major challenges for the water sector worldwide. Here we use a comparative case study to explore the long-term changes in the system-wide water and associated energy use in two different regions that encountered water shortage. In Australia, South East Queensland (SEQ) encountered a drought from 2001 to 2009, while Perth has experienced a decline in rainfall since the 1970s. This novel longitudinal study quantifies and compares the urban water consumption and the energy use of the water supply systems in SEQ and Perth during the period 2002 to 2014. Unlike hypothetical and long-term scenario studies, this comparative study quantifies actual changes in regional water consumption and associated energy, and explores the lessons learned from the two regions. In 2002, Perth had a similar per capita water consumption rate to SEQ and 48% higher per capita energy use in the water supply system. From 2002 to 2014, a strong effort of water conservation can be seen in SEQ during the drought, while Perth has been increasingly relying on seawater desalination. By 2014, even though the drought in SEQ had ended and the drying climate in Perth was continuing, the per capita water consumption in SEQ (266 L/p/d) was still 28% lower than that of Perth (368 L/p/d), while the per capita energy use in Perth (247 kWh/p/yr) had increased to almost five times that of SEQ (53 kWh/p/yr). This comparative study shows that within one decade, major changes in water and associated energy use occurred in regions that were similar historically. The very different "water-energy" trajectories in the two regions arose partly due to the type of water management options implemented, particularly the different emphasis on supply versus demand side management. This study also highlights the significant energy saving benefit of water conservation strategies (i.e. in SEQ, the energy saving was sufficient to offset the total energy use for seawater desalination and water recycling during the period.). The water-energy trajectory diagram provides a new way to illustrate and compare longitudinal water consumption and associated energy use within and between cities. PMID- 27395016 TI - Pironetin Binds Covalently to alphaCys316 and Perturbs a Major Loop and Helix of alpha-Tubulin to Inhibit Microtubule Formation. AB - Microtubule-targeting agents are among the most powerful drugs used in chemotherapy to treat cancer patients. Pironetin is a natural product that displays promising anticancer properties by binding to and potently inhibiting tubulin assembly into microtubules; however, its molecular mechanism of action remained obscure. Here, we solved the crystal structure of the tubulin-pironetin complex and found that the compound covalently binds to Cys316 of alpha-tubulin. The structure further revealed that pironetin perturbs the T7 loop and helix H8 of alpha-tubulin. Since both these elements are essential for establishing longitudinal tubulin contacts in microtubules, this result explains how pironetin inhibits the formation of microtubules. Together, our data define the molecular details of the pironetin binding site on alpha-tubulin and thus offer a promising basis for the rational design of pironetin variants with improved activity profiles. They further extend our knowledge on strategies evolved by natural products to target and perturb the microtubule cytoskeleton. PMID- 27395018 TI - Self-injection of household cleaning detergents into a ventriculoperitoneal shunt reservoir during a suicide attempt: a case report and literature review. AB - Self-injection of household cleaning detergents (more specifically, commercial toilet bowl cleaner) into the reservoir of a ventriculoperitoneal shunt (VPS) has never been reported in the neurosurgical literature. A right-handed 41-year-old female with a past medical history significant for bipolar depression (with multiple prior hospital admissions for suicide attempts) and pseudotumor cerebri (status-post VPS placement from a right frontal approach) successfully injected ~5 ml of toilet bowl cleaner into her ventricular shunt reservoir during a suicide attempt. She was found unresponsive by a family member 48 h after this event and presented to our hospital in moribund neurological condition (bilaterally fixed and dilated pupils with decerebrate posturing). Head computed tomography (CT) demonstrated marked ventriculomegaly. She was taken emergently to the operating room for placement of a left frontal ventriculostomy. Cerebrospinal fluid (CSF) sampled intraoperatively showed numerous Gram-positive cocci (later determined to be Staphylococcus epidermidis). For this reason, her right-sided shunt system was also removed in its entirety. She was treated with broad spectrum intravenous and intraventricular antibiotics for her bacterial ventriculitis and her CSF was aggressively drained to treat her hydrocephalus. Once her infection had resolved, the shunt was replaced (using a right parietal approach) and she went on to make an excellent neurological recovery. Here, the authors present the case of a patient who self-injected household cleaning detergents into her VPS reservoir-and, likely, the ventricular system-during a suicide attempt and subsequently developed hydrocephalus and ventriculitis. Following this infrequent clinical scenario, consideration should be given to temporary ventriculostomy placement and shunt removal. Moreover, in patients with a known history of psychiatric co-morbidities-and particularly those patients with prior suicide attempts-the neurosurgeon should give serious consideration to placing the shunt system in an anatomical region which is difficult for the patient to self-access based upon their handedness. PMID- 27395017 TI - Order-Disorder Transitions in the Cardiac Troponin Complex. AB - The troponin complex is a molecular switch that ties shifting intracellular calcium concentration to association and dissociation of actin and myosin, effectively allowing excitation-contraction coupling in striated muscle. Although there is a long history of muscle biophysics and structural biology, many of the mechanistic details that enable troponin's function remain incompletely understood. This review summarizes the current structural understanding of the troponin complex on the muscle thin filament, focusing on conformational changes in flexible regions of the troponin I subunit. In particular, we focus on order disorder transitions in the C-terminal domain of troponin I, which have important implications in cardiac disease and could also have potential as a model system for the study of coupled binding and folding. PMID- 27395019 TI - Anterior communicating artery division in the bifrontal basal interhemispheric approach. PMID- 27395020 TI - A mini-review on functional nucleic acids-based heavy metal ion detection. AB - Recent years have witnessed great progress in developing functional nucleic acids (FNAs)-based sensors for the detection of heavy metal ion. In this review, four types of the FNAs that most widely-used in heavy metal ions detection were briefly introduced and a dozen of recently published review articles which summarized those FNAs-based sensors were introduced. Particularly, according to the degree of automation and system integration, those FNAs-based sensors which belong to the lab-on-a-chip (LOC) category were reviewed in more detail by classifying them into six types such as microfluidic LOC system, microchip, lateral flow dipstick, personal glucose meter, microfluidic paper-based analytical devices (MUPADs) and disc-based analytical platform. After gave a brief description of the sensing strategies, properties, advantages or disadvantages of these FNAs-based sensors, existing problems and future perspectives were also discussed. PMID- 27395021 TI - [Candida biofilm-related infections]. AB - The number of biomedical devices (intravascular catheters, heart valves, joint replacements, etc.) that are implanted in our hospitals has increased exponentially in recent years. Candida species are pathogens which are becoming more significant in these kinds of infections. Candida has two forms of development: planktonic and in biofilms. A biofilm is a community of microorganisms which adhere to a surface and are enclosed by an extracellular matrix. This form of development confers a high resistance to the antimicrobial agents. This is the reason why antibiotic treatments usually fail and biomedical devices may have to be removed in most cases. Unspecific adhesion mechanisms, the adhesion-receptor systems, and an intercellular communication system called quorum sensing play an essential role in the development of Candida biofilms. In general, the azoles have poor activity against Candida biofilms, while echinocandins and polyenes show a greater activity. New therapeutic strategies need to be developed due to the high morbidity and mortality and high economic costs associated with these infections. Most studies to date have focused on bacterial biofilms. The knowledge of the formation of Candida biofilms and their composition is essential to develop new preventive and therapeutic strategies. PMID- 27395022 TI - [Update on invasive candidiasis in non-neutropenic critically ill adult patients]. AB - Invasive candidiasis in non-neutropenic critically ill patients remains a challenge for clinicians due to its association with high morbidity and mortality rates, increased incidence, and health-care costs. It is well known that early diagnosis and treatment are associated with a better prognosis. For these reasons a thorough update has been performed in this setting focused on recent Spanish epidemiology, new predictive scores and microbiological tests such as mannan antigen, mannan antibodies, Candida albicans germ-tube antibodies or (1->3)-beta D-glucan detection, molecular techniques for the detection of fungal-specific DNA, advances in antifungal treatment and educational programs in Spain. An early diagnostic and therapeutic algorithm is proposed based on the combination of scores and microbiological test. The aim of this review is to provide physicians with the best information available in order to improve the prognosis of these patients. PMID- 27395023 TI - [Invasive yeast infections in neutropenic patients]. AB - Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C.albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis. PMID- 27395024 TI - [Echinocandins: Applied pharmacology]. AB - The echinocandins share pharmacodynamic properties, although there are some interesting differences in their pharmacokinetic behaviour in the clinical practice. They are not absorbed by the oral route. They have a somewhat special distribution in the organism, as some of them can reach high intracellular concentrations while, with some others, the concentration is reduced. They are highly bound to plasma proteins, thus it is recommended to administer a loading dose for anidulafungin and caspofungin, although this procedure is not yet clear with micafungin. Echinocandins are excreted via a non-microsomal metabolism, so the urinary concentration is very low. Some carrier proteins that take part in the biliary clearance process are probably involved in the interactions described with caspofungin and micafungin. These two drugs must be used with caution in patients with severely impaired hepatic function, while all of them can be used without special precautions when there is renal impairment or the patient requires renal replacement therapy. PMID- 27395025 TI - [Invasive yeast infections in severely burned patients]. AB - Currently, there are few studies on candidaemia in the severely burned patient. These patients share the same risk factors for invasive fungal infections as other critically ill patients, but have certain characteristics that make them particularly susceptible. These include the loss of skin barrier due to extensive burns, fungal colonisation of the latter, and the use of hydrotherapy or other topical therapies (occasionally with antimicrobials). In addition, the increased survival rate achieved in recent decades in critically burned patients due to the advances in treatment has led to the increase of invasive Candida infections. This explains the growing interest in making an earlier and more accurate diagnosis, as well as more effective treatments to reduce morbidity and mortality of candidaemia in severe burned patients. A review is presented on all aspects of the burned patient, including the predisposition and risk factors for invasive candidiasis, pathogenesis of candidaemia, underlying immunodeficiency, local epidemiology and antifungal susceptibility, evolution and prognostic factors, as well as other non-Candida yeast infections. Finally, we include specific data on our local experience in the management of candidaemia in severe burned patients, which may serve to quantify the problem, place it in context, and offer a realistic perspective. PMID- 27395027 TI - Hybridization of photoanode and bioanode to enhance the current production of bioelectrochemical systems. AB - Bacterial extracellular electron transfer is one of the main bottlenecks in determining the efficiency of bioelectrochemical systems. Here, we report a photobioanode that combines carbon material with a photocatalyst (alpha-Fe2O3), utilizing visible light to accelerate biofilm formation and extracellular electron transfer in bioelectrochemical systems. Cyclic voltammetric studies of this photobioanode revealed active electron transfer at the anode/biofilm interface. The charge-transfer resistance of the anode/biofilm was ca. 46.6 Omega, which is half that of the unmodified anode. In addition, the results of confocal laser scanning microscopy and bacterial community analysis indicate that the photobioanode and light can accelerate biofilm formation and enrich exoelectrogens. When equipped in photo-bioelectrochemical systems, the start-up time was shortened from about 2.5 days to 1.1 days. The maximum current density of photo-bioelectrochemical systems was almost twice that of a control bioelectrochemical system. In addition, the current density of the photo-bio electrochemical cell (PBEC) showed almost no decrease after being subjected to 40 d of illumination. This photobioanode is therefore a cost-effective, energy clean, environment-friendly anode with high electrocatalytic activity and long term stability, which has broad prospects in various processes, including wastewater treatment, bioelectricity generation, bioelectricity synthesis, and hydrogen production. PMID- 27395026 TI - Intracellular and intercellular signaling networks in cancer initiation, development and precision anti-cancer therapy: RAS acts as contextual signaling hub. AB - Cancer initiation and development are increasingly perceived as systems-level phenomena, where intra- and inter-cellular signaling networks of the ecosystem of cancer and stromal cells offer efficient methodologies for outcome prediction and intervention design. Within this framework, RAS emerges as a 'contextual signaling hub', i.e. the final result of RAS activation or inhibition is determined by the signaling network context. Current therapies often 'train' cancer cells shifting them to a novel attractor, which has increased metastatic potential and drug resistance. The few therapy-surviving cancer cells are surrounded by massive cell death triggering a primordial adaptive and reparative general wound healing response. Overall, dynamic analysis of patient- and disease stage specific intracellular and intercellular signaling networks may open new areas of anticancer therapy using multitarget drugs, drugs combinations, edgetic drugs, as well as help design 'gentler', differentiation and maintenance therapies. PMID- 27395028 TI - Performance enhancement of zero valent iron based systems using depassivators: Optimization and kinetic mechanisms. AB - The long-term ability of Zero-Valent Iron (ZVI) in contaminant removal relies on the effectiveness of iron to serve as electron donor, which makes it a versatile remediation material. However, the formation of oxide and hydroxide layers results in passive layer on ZVI surface during contaminant removal hinders its reactivity. The focus of this research was to evaluate the performance of corrosive agents such as acetic acid (HAc), aluminium sulphate (Alum) and potassium chloride (KCl) as depassivators to overcome passivation for sustainability and longevity. Batch experiments using seven combinations of the above chemicals were conducted to optimize the dosage of depassivators based on passive layer removal. The influence of depassivators in catalytic activity of ZVI in removing Cr(6+) was evaluated. The passive layer on ZVI particles was characterized using Scanning Electron Microscopy (SEM) and confirmed by Energy Dispersive X-ray spectroscopy (EDAX) analysis. The major mechanisms in passive layer removal was found to be H(+) ion embrittlement followed by uniform depassivation when [HAc] was used and pitting corrosion when [Alum] and [KCl]were used. All the seven sets of chemicals enabled depassivation, but considering the criteria of maximum depassivation, catalytic activity and long term reactivity the depassivation treatments were effective in order as [HAc-Alum] > [HAc-Alum KCl] >[HAc] > [Alum] > [HAc-KCl] > [KCl] > [Alum-KCl]. The kinetic rate of ZVI using [HAc-Alum] and [Alum] was relatively unchanged over the pH range of 4-10, made it suitable for ex-situ remediation. This insignificant influence of initial pH in catalytic activity of ZVI along with the improvement in longevity and sustainability makes it suitable for effective water treatment applications. The present work has successfully demonstrated that chemical depassivation can restore considerable reactivity of ZVI in the existing permeable reactive barriers. PMID- 27395029 TI - Cr(VI) reduction coupled with anaerobic oxidation of methane in a laboratory reactor. AB - The process of anaerobic oxidation of methane (AOM) is globally important because of its contribution to the carbon cycle in the environment. Besides, microorganisms play important roles in the environmental fate of chromium. However, there have been no studies to date on the interaction between methane and chromium in batch reactor systems. In this study, biological Cr(VI) reduction was investigated using methane as the sole electron donor. Isotopic (13)CH4 in the batch experiments and long-term performance in the reactor demonstrated that Cr(VI) reduction is coupled with methane oxidation. High-throughput sequencing of the 16S rRNA genes demonstrated that the microbial community had changed substantially after Cr(VI) reduction. The populations of ANME-2d archaea were enhanced, and they became the only predominant AOM-related microbe. Interestingly, other bacteria with significant increases in abundance were not reported as having the ability to reduce Cr(VI). According to these results, two mechanisms were proposed: 1) Cr(VI) is reduced by ANME-2d alone; 2) Cr(VI) is reduced by unknown Cr(VI)-reducing microbes coupled with ANME-2d. This study revealed the potential relationship between Cr(VI) reduction and CH4 oxidation, and extended our knowledge of the relationship between the AOM process and biogeochemical cycles. PMID- 27395030 TI - A model for methane production in anaerobic digestion of swine wastewater. AB - A study was conducted using a laboratory-scale anaerobic sequencing batch digester to investigate the quantitative influence of organic loading rates (OLRs) on the methane production rate during digestion of swine wastewater at temperatures between 15 degrees C and 35 degrees C. The volumetric production rate of methane (Rp) at different OLRs and temperatures was obtained. The maximum volumetric methane production rates (Rpmax) were 0.136, 0.796, 1.294, 1.527 and 1.952 LCH4 L(-1) d(-1) at corresponding organic loading rates of 1.2, 3.6, 5.6, 5.6 and 7.2 g volatile solids L(-1) d(-1), respectively, which occurred at 15, 20, 25, 30 and 35 degrees C, respectively. A new model was developed to describe the quantitative relationship between Rp and OLR. In addition to the maximum volumetric methane production rate (Rpmax) and the half-saturation constant (KLR) commonly used in previous models such as the modified Stover-Kincannon model and Deng model, the new model introduced a new index (KD) that denoted the speed of volumetric methane production rate approaching the maximum as a function of temperature. The new model more satisfactorily described the influence of OLR on the rate of methane production than other models as confirmed by higher determination coefficients (R(2)) (0.9717-0.9900) and lower bias between the experimental and predicted data in terms of the root mean square error and the Akaike Information Criterion. Data from other published research also validated the applicability and generality of the new kinetic model to different types of wastewater. PMID- 27395031 TI - Network of nuclear receptor ligands in multiple sclerosis: Common pathways and interactions of sex-steroids, corticosteroids and vitamin D3-derived molecules. AB - Sex-steroids, corticosteroids and vitamin D3-derived molecules have all been subject to experimental studies and clinical trials in a plethora of autoimmune diseases. These molecules are all derived from cholesterol metabolites and are ligands for nuclear receptors. Ligation of these receptors results in direct regulation of multiple gene transcription involved in general homeostatic and adaptation networks, including the immune system. Indeed, the distinct ligands affect the function of both myeloid and lymphoid cells, eventually resulting in a less pro-inflammatory immune response which is considered beneficial in autoimmune diseases. Next to the immune system, also the central nervous system is prone to regulation by these nuclear receptor ligands. Understanding of the intricate interactions between sex-steroids, corticosteroids and vitamin D3 metabolites, on the one hand, and the immune and central nervous system, on the other hand, may reveal novel approaches to utilize these nuclear receptor ligands to full extent as putative treatments in multiple sclerosis, the prototypic immune-driven disease of the central nervous system. PMID- 27395032 TI - 2',5'-Oligoadenylate synthetase 1(OAS1) inhibits PRRSV replication in Marc-145 cells. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically destructive disease for global pig industry. Although its invasion mechanism is clear, the knowledge of pathogen and host interaction is less known. Here, we found that PPRSV infection led to induction of 2', 5'-oligoadenylate synthetase gene 1(OAS1), an important interferon-stimulated gene. More importantly, ectopic overexpression of OAS1 significantly restricted the replication of PRRSV in 24 and 36 h post-infection in Marc-145 cells, and indirect immunofluorescence assay with antibody against PRRSV N protein displayed significantly lower frequency of fluorescence stained cells and reduced cytopathogenic effects of PRRSV on OAS1 transfected Marc-145 cells. Meanwhile, knockdown of endogenous OAS1 increased the PRRSV ORF7 mRNA level to 1.6 and 1.7 times of that in control in 24 and 36 h post infection of PRRSV, and led to approximate 5.5 times increase of the frequency of fluorescence positive cells compared to negative control (p < 0.01). The obtained results strongly support a direct restriction function of OAS1 to PRRSV replication, which may contribute to the antiviral effect of the interferon system on PRRSV replication. PMID- 27395033 TI - Clinical and epidemiological characteristics of a patient infected with H5N6 avian influenza A virus. PMID- 27395035 TI - Role of recombinant human erythropoietin loading chitosan-tripolyphosphate nanoparticles in busulfan-induced genotoxicity: Analysis of DNA fragmentation via comet assay in cultured HepG2 cells. AB - Busulfan is one of the most effective chemotherapeutic agents used for the treatment of chronic myeloid leukemia. Busulfan is involved in secondary malignancy due to its genotoxic potential in normal tissues. As an alkylating agent busulfan can cause DNA damage by cross-linking DNAs and DNA and proteins, induces senescence in normal cells via transient depletion of intracellular glutathione (GSH) and subsequently by a continuous increase in reactive oxygen species (ROS) production. Erythropoietin, a glycoprotein widely used against drug induced anemia in cancerous patients and regulates hematopoiesis, has been shown to exert an important cyto-protective effect in many tissues. Recombinant human erythropoietin has been demonstrated to directly limit cell injury and ROS generation during oxidative stress. Furthermore, rhEPO decreased levels of pro apoptotic factor (Bax) and also increased expression of the anti-apoptotic factor Bcl2. According to EPO's short half-life and requirements for the frequently administration, finding the new strategies to attenuate its side effects is important. The aim of this study was to explore whether rhEPO loading chitosan tripolyphosphate nanoparticles protects against busulfan-induced genotoxicity in HepG2 cells. For this purpose cells were incubated with busulfan alone, regular rhEPO alone and regular rhEPO and CS-TPP-EPO nanoparticles along with busulfan in pre and co-treatment condition. Our results showed that busulfan induced a noticeable genotoxic effects in HepG2 cells (p<0.0001). Both regular rhEPO and CS TPP-EPO nanoparticles reduced the effects of busulfan significantly (p<0.0001) by reduction of the level of DNA damage via blocking ROS generation, and enhancement intracellular glutathione levels. CS-TPP-EPO nanoparticles were more effective than regular rhEPO in both pre and co-treatment conditions. In conclusion, our results show that administration of rhEPO and CS-TPP-EPO nanoparticles especially in the pre-treatment conditions, significantly decreased the level of DNA damage induced by busulfan, measured with the comet assay, in HepG2 cells compared to the regular rhEPO group. PMID- 27395034 TI - Comparative genomics of the human, macaque and mouse major histocompatibility complex. AB - The MHC is a highly polymorphic genomic region that encodes the transplantation and immune regulatory molecules. It receives special attention for genetic investigation because of its important role in the regulation of innate and adaptive immune responses and its strong association with numerous infectious and/or autoimmune diseases. The MHC locus was first discovered in the mouse and for the past 50 years it has been studied most intensively in both mice and humans. However, in recent years the macaque species have emerged as some of the more important and advanced experimental animal models for biomedical research into MHC with important human immunodeficiency virus/simian immunodeficiency virus and transplantation studies undertaken in association with precise MHC genotyping and haplotyping methods using Sanger sequencing and next-generation sequencing. Here, in this special issue on 'Macaque Immunology' we provide a short review of the genomic similarities and differences among the human, macaque and mouse MHC class I and class II regions, with an emphasis on the association of the macaque class I region with MHC polymorphism, haplotype structure and function. PMID- 27395036 TI - Stretching-induced nanostructures on shape memory polyurethane films and their regulation to osteoblasts morphology. AB - Programming such as stretching, compression and bending is indispensible to endow polyurethanes with shape memory effects. Despite extensive investigations on the contributions of programming processes to the shape memory effects of polyurethane, less attention has been paid to the nanostructures of shape memory polyurethanes surface during the programming process. Here we found that stretching could induce the reassembly of hard domains and thereby change the nanostructures on the film surfaces with dependence on the stretching ratios (0%, 50%, 100%, and 200%). In as-cast polyurethane films, hard segments sequentially assembled into nano-scale hard domains, round or fibrillar islands, and fibrillar apophyses. Upon stretching, the islands packed along the stretching axis to form reoriented fibrillar apophyses along the stretching direction. Stretching only changed the chemical patterns on polyurethane films without significantly altering surface roughness, with the primary composition of fibrillar apophyses being hydrophilic hard domains. Further analysis of osteoblasts morphology revealed that the focal adhesion formation and osteoblasts orientation were in accordance with the chemical patterns of the underlying stretched films, which corroborates the vital roles of stretching-induced nanostructures in regulating osteoblasts morphology. These novel findings suggest that programming might hold great potential for patterning polyurethane surfaces so as to direct cellular behavior. In addition, this work lays groundwork for guiding the programming of shape memory polyurethanes to produce appropriate nanostructures for predetermined medical applications. PMID- 27395037 TI - The structural development of primary cultured hippocampal neurons on a graphene substrate. AB - The potential of graphene-based nanomaterials as a neural interfacing material for neural repair and regeneration remains poorly understood. In the present study, the response to the graphene substrate by neurons was determined in a hippocampal culture model. The results revealed the growth and maturation of hippocampal cultures on graphene substrates were significantly improved compared to the commercial control. In details, graphene promoted growth cone growth and microtubule formation inside filopodia 24h after seeding as evidenced by a higher average number of filopodia emerging from growth cones, a longer average length of filopodia, and a larger growth cone area. Graphene also significantly boosted neurite sprouting and outgrowth. The dendritic length, the number of branch points, and the dendritic complex index were significantly improved on the graphene substrate during culture. Moreover, the spine density was enhanced and the maturation of dendritic spines from thin to stubby spines was significantly promoted on graphene at 21 days after seeding. Lastly, graphene significantly elevated the synapse density and synaptic activity in the hippocampal cultures. The present study highlights graphene's potential as a neural interfacing material for neural repair and regeneration and sheds light on the future biomedical applications of graphene-based nanomaterials. PMID- 27395038 TI - The amphoteric effect on friction between the bovine cartilage/cartilage surfaces under slightly sheared hydration lubrication mode. AB - The amphoteric effect on the friction between the bovine cartilage/cartilage contacts has been found to be highly sensitive to the pH of an aqueous solution. The cartilage surface was characterized using a combination of the pH, wettability, as well as the interfacial energy and friction coefficient testing methods to support lamellar-repulsive mechanism of hydration lubrication. It has been confirmed experimentally that phospholipidic multi-bilayers are essentially described as lamellar frictionless lubricants protecting the surface of the joints against wear. At the hydrophilicity limit, the low friction would then be due to (a) lamellar slippage of bilayers and (b) a short-range (nanometer-scale) repulsion between the interfaces of negatively charged (PO4(-)) cartilage surfaces, and in addition, contribution of the extracellular matrix (ECM) collagen fibers, hyaluronate, proteoglycans aggregates (PGs), glycoprotein termed lubricin and finally, lamellar PLs phases. In this paper we demonstrate experimentally that the pH sensitivity of cartilage to friction provides a novel concept in joint lubrication on charged surfaces. PMID- 27395039 TI - Investigation of extracellular polymeric substances (EPS) properties of P. aeruginosa and B. subtilis and their role in bacterial adhesion. AB - Extracellular polymeric substances (EPS) matrix in biofilm poses important functions such as a diffusion barrier to antimicrobial agents so that biofilm cells are more difficult to completely eliminate. Therefore, biofilm cells exhibit enhanced resilience unlike planktonic cells, and are more difficult to completely eliminate. In order to obtain a comprehensive understanding of bacterial adhesion to surfaces, knowledge of the composition and conformational properties of EPS produced during growth and biofilm formation is required, since their adhesive and conformational properties remain poorly understood at molecular level. Present study has provided further insights into identifying compositional and conformational properties of EPS produced by planktonic and biofilm cells of B. subtilis and P. aeruginosa. Various spectroscopy analyses showed that EPS produced by the two different species were chemically dissimilar. More proteinaceous compounds were present in EPS from B. subtilis, while EPS from P. aeruginosa were characterized by greater carbohydrate components. However, relative proportions of polysaccharides and/or proteins constituents varied with the growth mode of the bacteria. AFM was then used to probe the adhesive nature of EPS produced by the bacteria by using Single Molecule Force Spectroscopy (SMFS). Comparison of the two bacterial species indicated that the presence of polysaccharides promoted the adhesion strength of the EPS while proteins had lesser adherence effects. Comparison of the two growth modes for the same bacterial strain also indicated that greater EPS production and enhanced cellular adhesion are associated with biofilm growth. PMID- 27395040 TI - Prevalence and risk factors of chronic rhinosinusitis in South Korea according to diagnostic criteria. AB - BACKGROUND: We aimed to compare the prevalence and risk factors of chronic rhinosinusitis (CRS) using two different diagnostic criteria with the same statistical data from the Korean National Health and Nutrition Examination Survey in 2009. METHODS: Symptom-based CRS was defined as CRS diagnosed by questionnaires related to nasal symptoms. Endoscopy-based CRS was defined based on endoscopic findings and nasal symptoms of symptom-based CRS. RESULTS: The overall prevalence of CRS based on the different diagnostic criteria was as follows: symptom-based CRS was 10.78% (797 of 7,394) and endoscopy-based CRS was 1.20% (88 of 7,343). Comparing symptom-based CRS to endoscopy-based CRS showed slight agreement (kappa = 0.183 (0.150-0.216, 95% confidence interval)). Allergic rhinitis was identified as a common risk factor for CRS based on the two diagnostic criteria. CONCLUSIONS: The prevalence and risk factors of CRS were quite different from each other according to the different criteria, even in the same population. Therefore, it would be important to consider what specific diagnostic criteria have been adopted in the studies comparing the prevalence of CRS. PMID- 27395041 TI - Not here, there! Possible referential gesturing during allogrooming by wild bonnet macaques, Macaca radiata. AB - Intentional referential gestures, a fundamental building block of symbolic human language, have been reported from a range of species, including non-human primates. While apes are known to spontaneously use intentional gestures, only captive macaques, amongst non-ape primates, appear to intentionally display learnt gestures. On the other hand, referential gestures have so far been reported only in chimpanzees, amongst non-human primates. We document here, for the first time, potentially referential gesturing, used intentionally as well, in a monkey species, the bonnet macaque Macaca radiata, in the wild. Bonnet macaques use four distinct actions during allogrooming, possibly to indicate a particular body part intended to be groomed. These acts were successful in drawing the recipients' attention to the indicated part, which they began to groom subsequently. This study enriches our understanding of non-ape primate gestural communication and adds to the growing evidence for early human language-like capacities in non-human species. PMID- 27395042 TI - A continuous-time model of centrally coordinated motion with random switching. AB - This paper considers differential problems with random switching, with specific applications to the motion of cells and centrally coordinated motion. Starting with a differential-equation model of cell motion that was proposed previously, we set the relaxation time to zero and consider the simpler model that results. We prove that this model is well-posed, in the sense that it corresponds to a pure jump-type continuous-time Markov process (without explosion). We then describe the model's long-time behavior, first by specifying an attracting steady state distribution for a projection of the model, then by examining the expected location of the cell center when the initial data is compatible with that steady state. Under such conditions, we present a formula for the expected velocity and give a rigorous proof of that formula's validity. We conclude the paper with a comparison between these theoretical results and the results of numerical simulations. PMID- 27395043 TI - The critical domain size of stochastic population models. AB - Identifying the critical domain size necessary for a population to persist is an important question in ecology. Both demographic and environmental stochasticity impact a population's ability to persist. Here we explore ways of including this variability. We study populations with distinct dispersal and sedentary stages, which have traditionally been modelled using a deterministic integrodifference equation (IDE) framework. Individual-based models (IBMs) are the most intuitive stochastic analogues to IDEs but yield few analytic insights. We explore two alternate approaches; one is a scaling up to the population level using the Central Limit Theorem, and the other a variation on both Galton-Watson branching processes and branching processes in random environments. These branching process models closely approximate the IBM and yield insight into the factors determining the critical domain size for a given population subject to stochasticity. PMID- 27395044 TI - Involvement of Cholinergic and Adrenergic Receptors in Pathogenesis and Inflammatory Response Induced by Alpha-Neurotoxin Bot III of Scorpion Venom. AB - Bot III neurotoxin is the most lethal alpha neurotoxin purified from Buthus occitanus tunetanus scorpion venom. This toxin binds to the voltage-gated sodium channel of excitable cells and blocks its inactivation, inducing an increased release of neurotransmitters (acetylcholine and catecholamines). This study aims to elucidate the involvement of cholinergic and adrenergic receptors in pathogenesis and inflammatory response triggered by this toxin. Injection of Bot III to animals induces an increase of peroxidase activities, an imbalance of oxidative status, tissue damages in lung parenchyma, and myocardium correlated with metabolic disorders. The pretreatment with nicotine (nicotinic receptor agonist) or atropine (muscarinic receptor antagonist) protected the animals from almost all disorders caused by Bot III toxin, especially the immunological alterations. Bisoprolol administration (selective beta1 adrenergic receptor antagonist) was also efficient in the protection of animals, mainly on tissue damage. Propranolol (non-selective adrenergic receptor antagonist) showed less effect. These results suggest that both cholinergic and adrenergic receptors are activated in the cardiopulmonary manifestations induced by Bot III. Indeed, the muscarinic receptor appears to be more involved than the nicotinic one, and the beta1 adrenergic receptor seems to dominate the beta2 receptor. These results showed also that the activation of nicotinic receptor leads to a significant protection of animals against Bot III toxin effect. These findings supply a supplementary data leading to better understanding of the mechanism triggered by scorpionic neurotoxins and suggest the use of drugs targeting these receptors, especially the nicotinic one in order to counteract the inflammatory response observed in scorpion envenomation. PMID- 27395045 TI - Astragaloside IV Inhibits the Inflammatory Injury of Chicken Type II Pneumocytes Induced by Avian Pathogenic Escherichia coli. AB - Avian pathogenic Escherichia coli (APEC) induces septicemia in chickens by invading type II pneumocytes after breaching the blood-air barrier. Type II pneumocytes play an important role in maintaining the function of the blood-air barrier. Astragaloside IV has been shown in previous studies to have an anti inflammatory effect. To explore whether astragaloside IV can inhibit APEC-induced injury in chicken type II pneumocytes, cells were infected with APEC-O78. The results showed that astragaloside IV significantly reduced cell damage in chicken type II pneumocytes induced by APEC-O78 by downregulating the production of TNF alpha and IL-1beta, upregulating the secretion of IL-4 and IL-10, suppressing the mRNA levels of TLR-4, TLR-5, ERK, and p38 of chicken type II pneumocytes as well as inhibiting bacterial adhesion and F-actin cytoskeleton polymerization. These results suggest that astragaloside IV may be useful in novel pharmaco-therapeutic approaches to the treatment of chicken colibacillosis. PMID- 27395046 TI - Asiatic Acid Inhibits Lipopolysaccharide-Induced Acute Lung Injury in Mice. AB - Asiatic acid (AA), a major triterpene isolated from Centella asiatica (L.) Urban, is known to exert various pharmacological activities, including anti-inflammatory and antioxidant effects. The aim of this study was to evaluate the anti inflammatory effects of AA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and clarify the underlying mechanisms. Lung pathological changes were assessed by H&E staining. The myeloperoxidase (MPO) activity was detected by MPO assay. The levels of inflammatory cytokines were measured by ELISA. TLR4 and NF kB expression was detected by Western blot analysis. AA obviously inhibited LPS induced lung histopathological changes, MPO activity, and inflammatory cell numbers in bronchoalveolar lavage fluid (BALF). Treatment of AA also inhibited LPS-induced TNF-alpha, IL-6, and IL-1beta production. Furthermore, Western blot analysis showed that AA inhibited LPS-induced TLR4 expression and NF-kB activation. In conclusion, AA inhibited LPS-induced ALI in mice by inhibiting inflammatory cytokine production, which is mediated via blocking of the TLR4/NF kB signaling pathway. PMID- 27395047 TI - Population Pharmacokinetics of Tracers: A New Tool for Medical Imaging? AB - Positron emission tomography-computed tomography is a medical imaging method measuring the activity of a radiotracer chosen to accumulate in cancer cells. A recent trend of medical imaging analysis is to account for the radiotracer's pharmacokinetic properties at a voxel (three-dimensional-pixel) level to separate the different tissues. These analyses are closely linked to population pharmacokinetic-pharmacodynamic modelling. Kineticists possess the cultural background to improve medical imaging analysis. This article stresses the common points with population pharmacokinetics and highlights the methodological locks that need to be lifted. PMID- 27395048 TI - Persons Who Failed to Obtain Colorectal Cancer Screening Despite Participation in an Evidence-Based Intervention. AB - In a previous report, we demonstrated the efficacy of an educational intervention focused on increasing colorectal cancer screening rates among African Americans. Despite participating in the intervention, however, nearly two-thirds of participants did not seek and receive screening. Participants were African Americans over age 49 (N = 257) who had not been screened for colorectal cancer according to guidelines. At baseline, participants completed tests measuring fatalism, perceived stress, self-esteem, attitudes/benefits/barriers, social support, and social network diversity. Those who completed the educational intervention were followed up by telephone to learn if they had been screened. We compared the scores on the psychometric tests of the participants who had been screened against the scores of those who had not. Only the mean scores on the attitudes, benefits, and barriers scale distinguished participants who had been screened from those who had not (p = 0.0816 on bivariate testing and p = 0.0276 in the logistic regression model). Social interaction among participants or social cognitive learning may have played a role in determining which participants were screened, but we were not able to demonstrate this. The major factor distinguishing participants who were not screened was their attitude toward screening at baseline. There is a subset of African Americans who are persistently resistant to screening, and their perspective in this regard must be addressed if colorectal cancer disparities are to be reduced. PMID- 27395049 TI - Stimulating Effect of Sclareol on Suicidal Death of Human Erythrocytes. AB - BACKGROUND/AIMS: The diterpene alcohol Sclareol has been proposed for the treatment of malignancy. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal cell death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the triggering of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, p38 kinase and casein kinase 1alpha. The present study explored, whether Sclareol induces eryptosis and, if so, shed light on the mechanisms involved. METHODS: Phosphatidylserine abundance at the erythrocyte surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3 fluorescence, abundance of reactive oxygen species (ROS) from 2',7' dichlorodihydrofluorescein diacetate (DCFDA)-dependent fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Hemolysis was estimated from haemoglobin concentration in the supernatant. RESULTS: A 48 hours exposure of human erythrocytes to Sclareol (>= 50 uM) significantly increased the percentage of annexin-V-binding cells without significantly modifying the average forward scatter, DCF-fluorescence or ceramide abundance. Sclareol (>= 50 uM) further triggered hemolysis. Sclareol (100 uM) significantly increased Fluo3 fluorescence, but the effect of Sclareol on annexin-V-binding was not significantly blunted by removal of extracellular Ca2+. Instead, the effect of Sclareol on annexin-V-binding was significantly blunted in the presence of p38 kinase inhibitor skepinone (2 uM) and in the presence of casein kinase 1alpha inhibitor D4476 (10 uM). CONCLUSIONS: Sclareol triggers phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to activation of p38 kinase and casein kinase 1alpha. PMID- 27395050 TI - Psychospiritual Resiliency: Enhancing Mental Health and Ecclesiastical Collaboration in Caring for Those Experiencing Dissociative Phenomena. AB - Trauma can oftentimes be a catalyst for changes in an individual's religious and spiritual beliefs. Beliefs about the cause of the trauma, for instance, may include attributions of possessing spirits, and are to be found in an increasingly pluralistic and multicultural society. Such preternatural explanations may be referred to as dissociative identity disorder, possession form. Unwittingly, an overreliance on neurobiological explanations and relegation of cultural idioms of distress may diminish effective collaboration with ecclesiastical authorities. Concomitantly, ecclesiastical experts are confronted with bewildering posttrauma dissociative symptomatology, and may not be prepared as diagnosticians to rule out psychobiological explanations. In both instances, client care may be compromised. Noteworthy, the current investigation integrates the author's participant observation research at the Vatican's school of Exorcism in Rome, Italy. PMID- 27395051 TI - Religious Involvement and Depression: The Mediating Effect of Relational Spirituality. AB - Multiple studies have examined the relationship between religious involvement and depression. Many of these investigations reveal a negative correlation between these constructs. Several others yield either no association or a positive correlation. In this article, we discuss possible explanations for these discrepant findings. We investigate the degree to which relational spirituality factors mediate the relationship between religious involvement and depression in a sample of graduate students. Results indicated that spiritual instability and disappointment in God were distinct predictors of depression over and above the predictive strength of religious involvement. Implications for training and conceptualization are discussed. PMID- 27395052 TI - TREMOR12: An Open-Source Mobile App for Tremor Quantification. AB - BACKGROUND: Evaluating the effect of treatment of tremor is mostly performed with clinical rating scales. Mobile applications facilitate a more rapid, objective, and quantitative evaluation of treatment effect. Existing mobile apps do not offer raw data access, which limits algorithm development. OBJECTIVE: To develop a novel open-source mobile app for tremor quantification. METHODS: TREMOR12 is an open-source mobile app that samples acceleration, rotation, rotation speed, and gravity, each in 3 axes and time-stamped in a frequency up to 100 Hz. The raw measurement data can be exported as a comma-separated value file for further analysis in the TREMOR12P data processing module. The app was evaluated with 3 patients suffering from essential tremor, who were between 55 and 71 years of age. RESULTS: This proof-of-concept study shows that the TREMOR12 app is able to detect and register tremor characteristics such as acceleration, rotation, rotation speed, and gravity in a simple and nonburdensome way. The app is compatible with current regulatory oversight by the European Union (MEDDEV regulations) and the Food and Drug Administration (FDA) guidance on mobile medical applications. CONCLUSION: TREMOR12 offers low-cost tremor quantification for research purposes and algorithm development, and may help to improve treatment evaluation. PMID- 27395053 TI - Identification of Novel Compound Mutations in PLA2G6-Associated Neurodegeneration Patient with Characteristic MRI Imaging. AB - Neurodegeneration with brain iron accumulation comprises a heterogeneous group of disorders characterized clinically by progressive motor dysfunction. Accurate identification of de novo and rare inherited mutations is important for determining causative genes of undiagnosed neurological diseases. In the present study, we report a unique case with cerebellar ataxia symptoms and social communication difficulties in an intermarriage family. MRI showed a marked cerebellar atrophy and the "eye-of-the-tiger"-like sign in the medial globus pallidus. Potential genetic defects were screened by whole-exome sequencing (WES) for the patient and four additional family members. A previously undescribed de novo missense mutation (c.1634A>G, p.K545R) in the exon 12 of the PLA2G6 gene was identified. A second rare variant c.1077G>A at the end of exon 7 was also identified, which was inherited from the mother, and resulted in a frame-shift mutation (c.1074_1077del.GTCG) due to an alternative splicing. In conclusion, the identification of the "eye-of-the-tiger"-like sign in the globus pallidus of the patient expands the phenotypic spectrum of PLA2G6-associated disorders and reveals its value in differential diagnosis of PLA2G6-associated disorders. PMID- 27395054 TI - The impact of thoracic load carriage up to 45 kg on the cardiopulmonary response to exercise. AB - PURPOSE: The purposes of this experiment were to, first, document the effect of 45-kg thoracic loading on peak exercise responses and, second, the effects of systematic increases in thoracic load on physiological responses to submaximal treadmill walking at a standardized speed and grade. METHODS: On separate days, 19 males (age 27 +/- 5 years, height 180.0 +/- 7.4 cm, mass 86.9 +/- 15.1 kg) completed randomly ordered graded exercise tests to exhaustion in loaded (45 kg) and unloaded conditions. On a third day, each subject completed four randomly ordered, 10-min bouts of treadmill walking at 1.34 m s(-1) and 4 % grade in the following conditions: unloaded, and with backpacks weighted to 15, 30, and 45 kg. RESULTS: With 45-kg thoracic loading, absolute oxygen consumption ([Formula: see text]), minute ventilation, power output, and test duration were significantly decreased at peak exercise. End-inspiratory lung volume and tidal volume were significantly reduced with no changes in end-expiratory lung volume, breathing frequency, and the respiratory exchange ratio. Peak end-tidal carbon dioxide and the ratio of alveolar ventilation to carbon dioxide production were similar between conditions. The reductions in peak physiological responses were greater than expected based on previous research with lighter loads. During submaximal treadmill exercise, [Formula: see text] increased (P < 0.05) by 11.0 (unloaded to 15 kg), 14.5 (15-30 kg), and 18.0 % (30-45 kg) showing that the increase in exercise [Formula: see text] was not proportional to load mass. CONCLUSION: These results provide further insight into the specificity of physiological responses to different types of load carriage. PMID- 27395055 TI - Myeloid Sarcoma: Presenting with Massive Cervical and Inguinal Lymphadenopathy. AB - A 21 year old Active Duty Marine presented with acute onset of diffuse lymphadenopathy and B-symptoms. Biopsy was conducted which demonstrated myeloid sarcoma. Myeloid sarcoma is diagnostic for AML but is only present in 2-8 % of patients with AML. Our article presents a classic presentation and histologic appearance and discusses the current status of the literature. PMID- 27395056 TI - The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells. AB - BACKGROUND: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. METHODS: The expression of IL-18, HMGB1 and alpha-smooth muscle actin (alpha-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting. Plasma concentrations of IL-18 and HMGB1 were measured using the ELISA kit. Cultured human aortic VICs were used as an in vitro model. RESULTS: Immunohistochemistry and immunoblotting revealed increased levels of IL-18, HMGB1 and alpha-SMA in calcific valves. Circulating IL-18 and HMGB1 levels were also higher in CAVD patients. In vitro, IL-18 induced upregulation of HMGB1 and alpha-SMA in VICs. Moreover, IL-18 induced secretion of HMGB1 to the extracellular space and activation of nuclear factor kappa-B (NF-kappaB). Blockade of NF-kappaB abrogated the upregulation and release of HMGB1 induced by IL-18. Whereas HMGB1 inhibition attenuated the IL-18-induced expression of alpha SMA, HMGB1 enhanced the effect of IL-18. CONCLUSIONS: We demonstrated for the first time that both tissue and plasma levels of IL-18 and HMGB1 were increased in patients with CAVD. Mechanically, HMGB1 mediated IL-18-induced VIC myofibroblastic transition. PMID- 27395057 TI - Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases. AB - Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy. PMID- 27395058 TI - GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells. AB - Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-beta superfamily. Recent studies confirmed that GDF11 plays an important role in regulating the regeneration of brain, skeletal muscle, and heart during aging; however, its role in bone metabolism remains unclear. Thus, the aim of this study was to determine the effects of GDF11 on bone metabolism, including bone formation and bone resorption, both in vitro and in vivo. Our results showed that GDF11 inhibited osteoblastic differentiation of bone marrow mesenchymal stem cells in vitro. Mechanistically, GDF11 repressed Runx2 expression by inducing SMAD2/3 phosphorylation during osteoblast differentiation. Moreover, intraperitoneal injection of GDF11 inhibited bone formation and accelerated age related bone loss in mice. Our results also showed that GDF11 had no effect on osteoclast differentiation or bone resorption both in vitro and in vivo. These results provide a further rationale for the therapeutic targeting of GDF11 for the treatment of age-related osteoporosis. PMID- 27395059 TI - Six Weeks of Daily Abaloparatide Treatment Increased Vertebral and Femoral Bone Mineral Density, Microarchitecture and Strength in Ovariectomized Osteopenic Rats. AB - Abaloparatide is a novel, potent and selective activator of parathyroid hormone receptor 1 (PTHR1) under clinical development for the treatment of osteoporosis. We assessed the effect of 6 weeks of abaloparatide on bone mass, microarchitecture, quality and strength in ovariectomized (OVX) rats. After 8 weeks of post-surgical bone depletion (baseline), OVX rats (n = 20-21/group) received daily subcutaneous vehicle (OVX-Veh) or abaloparatide at 5 or 20 ug/kg. Sham-operated control rats (n = 24) received vehicle. Areal bone mineral density (aBMD) of the lumbar spine (L4), total femur and femur diaphysis was measured at baseline and after 6 weeks of treatment. Femur and vertebral bone architecture and mechanical properties were assessed at the end of the treatment phase. At baseline, OVX-Veh rats exhibited significantly lower aBMD relative to Sham controls. Treatment of OVX rats with abaloparatide at 5 or 20 ug/kg/day increased aBMD dose-dependently in the lumbar spine, total femur and femur diaphysis to levels exceeding OVX-Veh or Sham controls. The abaloparatide 5 and 20 ug/kg groups had improved trabecular microarchitecture relative to OVX vehicle, with trabecular BV/TV exceeding OVX-Veh control values by 57 and 78 % (respectively) at the lumbar spine, and by 145 and 270 % at the distal femur. Femur diaphyseal cortical volume and thickness were significantly greater in the abaloparatide 20 ug/kg group relative to OVX vehicle or Sham controls. Bone strength parameters of the femur diaphysis, femur neck and L4 vertebra were significantly improved in the OVX-ABL groups relative to OVX-Veh controls. Bone mass-strength relationships and estimated intrinsic strength properties suggested maintained or improved bone quality with abaloparatide. These data demonstrate skeletal restoration via abaloparatide treatment of osteopenic OVX rats, in association with improved trabecular microarchitecture, cortical geometry and bone strength at sites that have clinical relevance in patients with osteoporosis. PMID- 27395060 TI - One executive function never comes alone: monitoring and its relation to working memory, reasoning, and different executive functions. AB - Monitoring is involved in many daily tasks and is described in several theoretical approaches of executive functioning. This study investigated the relative relationship of cognitive processes that are theoretically relevant to monitoring, such as concept formation, reasoning, working memory, and general cognitive control functions. Data from 699 participants who performed the Balanced Switching Task, aiming at capturing monitoring, were used. Subsamples also performed standard tasks assessing the processes assumed to be related to monitoring. Structural equation modeling revealed that general cognitive control processes are particularly relevant. They mediate the relationship between working memory, reasoning, and monitoring. Updating and maintaining information, as well as concluding from information which strategies can guide behavior toward predefined goals, is required for the ability to exert general cognitive control, which again may be relevant for implementing strategies in a goal-directed way. Together, these processes seem to be necessary to adequately monitor behavior in complex tasks. PMID- 27395061 TI - Propagation of dissection in a residually-stressed artery model. AB - This paper studies dissection propagation subject to internal pressure in a residually-stressed two-layer arterial model. The artery is assumed to be infinitely long, and the resultant plane strain problem is solved using the extended finite element method. The arterial layers are modelled using the anisotropic hyperelastic Holzapfel-Gasser-Ogden model, and the tissue damage due to tear propagation is described using a linear cohesive traction-separation law. Residual stress in the arterial wall is determined by an opening angle [Formula: see text] in a stress-free configuration. An initial tear is introduced within the artery which is subject to internal pressure. Quasi-static solutions are computed to determine the critical value of the pressure, at which the dissection starts to propagate. Our model shows that the dissection tends to propagate radially outwards. Interestingly, the critical pressure is higher for both very short and very long tears. The simulations also reveal that the inner wall buckles for longer tears, which is supported by clinical CT scans. In all simulated cases, the critical pressure is found to increase with the opening angle. In other words, residual stress acts to protect the artery against tear propagation. The effect of residual stress is more prominent when a tear is of intermediate length ([Formula: see text]90[Formula: see text] arc length). There is an intricate balance between tear length, wall buckling, fibre orientation, and residual stress that determines the tear propagation. PMID- 27395062 TI - Transcriptome sequencing and comparative analysis of Schizochytrium mangrovei PQ6 at different cultivation times. AB - OBJECTIVE: The heterotrophic marine microalga, Schizochytrium mangrovei PQ6, synthesizes large amounts of polyunsaturated fatty acids (PUFAs) with possible nutritional applications. We characterized the transcriptome of S. mangrovei PQ6, focusing on lipid metabolism pathways throughout growth. RESULT: Cell growth, total lipid, and docosahexaenoic acid (DHA, 22:6n-3) contents of S. mangrovei PQ6 in 500 ml batch cultures rapidly increased on day 1 in cultivation and reached their maximum levels on day 5. Maximum lipid accumulation in 500 ml batch cultures occurred on day 5, with total lipid and DHA contents reaching 33.2 +/- 1.25% of dry cell weight (DCW) and 136 mg/g DCW, respectively. 11,025 unigenes, 28,617 unigenes and 18,480 unigenes from the transcriptomes of samples collected on day 1, 3, and 5 in cultivation were identified, respectively. These unigenes of the three samples were further assembled into 30,782 unigenes with an average size of 673 bp and N50 of 950 bp, and a total of 9,980 unigenes were annotated in public protein databases. 93 unigenes involved in lipid metabolism in which expression patterns corresponded with total lipid and DHA accumulation patterns were identified. CONCLUSION: The possible roles of PUFAs pathways, such as those mediated by fatty acid synthase, polyketide synthase, and desaturase/elongase, co exist in S. mangrovei PQ6. PMID- 27395063 TI - Improvement in the thermostability of chitosanase from Bacillus ehimensis by introducing artificial disulfide bonds. AB - OBJECTIVE: To determine the effects of artificial disulfide bridges on the thermostability and catalytic efficiency of chitosanase EAG1. RESULTS: Five artificial disulfide bridges were designed based on the structural information derived from the three-dimensional (3-D) model of chitosanase EAG1. Two beneficial mutants (G113C/D116C, A207C-L286C) were located in the flexible surface loop region, whereas the similar substitutions introduced in alpha helices regions had a negligible effect. Mut5, the most active mutant, had a longer half-life at 50 degrees C (from 10.5 to 69.3 min) and a 200 % higher catalytic efficiency (K cat/K m) than that of the original EAG1. CONCLUSIONS: The contribution of disulfide bridges to enzyme thermostability is mainly dependent on its location within the polypeptide chain. Strategical placement of a disulfide bridge in flexible regions provides a rigid support and creation of a protected microenvironment, which is effective in improving enzyme's thermostability and catalytic efficiency. PMID- 27395064 TI - Engineering a glycerol utilization pathway in Corynebacterium glutamicum for succinate production under O2 deprivation. AB - OBJECTIVE: To explore the glycerol utilization pathway in Corynebacterium glutamicum for succinate production under O2 deprivation. RESULT: Overexpression of a glycerol facilitator, glycerol dehydrogenase and dihydroxyacetone kinase from Escherichia coli K-12 in C. glutamicum led to recombinant strains NC-3G diverting glycerol utilization towards succinate production under O2 deprivation. Under these conditions, strain NC-3G efficiently consumed glycerol and produced succinate without growth. The recombinant C. glutamicum utilizing glycerol as the sole carbon source showed higher intracellular NADH/NAD(+) ratio compare with utilizing glucose. The mass conversion of succinate increased from 0.64 to 0.95. Using an anaerobic fed-batch fermentation process, the final strain produced 38.4 g succinate/l with an average yield of 1.02 g/g. CONCLUSIONS: The metabolically engineered strains showed an efficient succinate production using glycerol as sole carbon source under O2 deprivation. PMID- 27395065 TI - Biochemical characterization of an isoform of GDP-D-mannose-4,6-dehydratase from Mortierella alpina. AB - OBJECTIVE: To clarify the molecular mechanism of GDP-L-fucose biosynthesis in Mortierella alpina. RESULTS: Analysis of the M. alpina genome suggests that there were two isofunctional GDP-D-mannose-4,6-dehydratase genes (GMD1 and GMD2) that have never been found in a microorganism before. GMD2 was expressed heterologously in Escherichia coli and purified to homogeneity. The addition of exogenous NAD(+) or NADP(+) was not essential for GMD2 activity. GMD2 may have considerable importance for GDP-L-fucose biosynthesis under nitrogen starvation. The transcriptional regulation of GMD1 may be more susceptible to GDP and GTP than that of GMD2. Significant changes were observed in the concentration of GDP L-fucose (30 and 36 % inhibition respectively) and total fatty acids (18 and 12 % inhibition respectively) in M. alpina grown on GMD inhibitors medium, which suggests that GDP-L-fucose is functionally significant in lipid metabolism. CONCLUSIONS: This is the first time that an isofunctional GDP-D-mannose-4,6 dehydratase has been characterized in a microorganism. PMID- 27395066 TI - [Not Available]. PMID- 27395068 TI - Intraductal injection as an effective drug delivery route in the management of salivary gland diseases. AB - While conservative approaches for chronic sialoadenitis are in current use, the utility of intraductal injection therapy remains unclear. The purpose of this study is to provide evidence that substances delivered through intraductal injection of the salivary gland are able to be effectively distributed throughout the gland. Methylene blue dye (0.1 %) was injected intraductally into a porcine parotid gland (5 ml) of one group and the porcine submandibular gland (1 or 2 ml, n = 6 for each preparation) of another group. After the injection, the ductal systems were evaluated, sectioned, and observed microscopically. Color area analysis was performed on submandibular gland sections, and the infiltration ratio of the dye was calculated. The papillae of both Stensen's and Wharton's duct openings were easily identified with intraductally delivered methylene blue dye. The dye infiltration began from the central ductal region of the gland and could be easily observed to gradually disperse to the peripheral regions in each acinar. There were no statistically significant differences in infiltration ratios between anterior, midline, and posterior section of the submandibular gland. Also, there were no statistically significant differences in the ratios between 1 and 2 ml injections at all the three section positions. This study demonstrated that desired substances can be evenly delivered throughout the salivary gland through intraductal injections. The use of intraductal injections might serve as a potential therapeutic procedure in the management of salivary gland diseases. PMID- 27395067 TI - Pregnancy Outcome in Women with Obstetric and Thrombotic Antiphospholipid Syndrome-A Retrospective Analysis and a Review of Additional Treatment in Pregnancy. AB - Antiphospholipid syndrome (APS) is associated with pregnancy complications such as recurrent early fetal loss (RFL), fetal death, preeclampsia (PE), and intrauterine growth restriction (obstetric APS/OAPS). Other clinical manifestations are venous and/or arterial thromboses (thrombotic APS/TAPS). The data of 37 pregnancies with OAPS and 37 pregnancies with TAPS were analyzed and compared. Overall, the most frequent APS antibodies (aPl) were LA as well as "triple-positivity"; LA antibodies were significantly more frequent in women with TAPS (67.6 % TAPS vs. 29.7 % OAPS, p < 0.010), whereas "triple-positivity" was significantly more seen in women with OAPS (40.5 % OAPS vs. 13.5 % TAPS, p < 0.010). Adequate therapy has been administered in nearly all pregnancies with TAPS, whereas in 18.9 % of pregnancies with OPS, no therapy has been given at all. One woman in OAPS and four women in TAPS were treated with plasmapheresis and immunoadsorption. There was no significant association between adverse obstetric outcome and therapy. The most frequent pregnancy complications were RFL in the OAPS group (32.4 vs. 13.5 % in TAPS) and PE in the TAPS group (18.9 % in OAPS and TAPS, respectively). The data of our study showed that pregnancies with OAPS and TAPS have a similar rate of pregnancy complications. However, pregnancies with OAPS tend to have rather RFL. Although we were not able to reveal a significant association with adverse obstetric outcome, it seems that the current adequate therapy for APS in pregnancy, consisting of LDA and LMWH, might rather prevent the development of RFL. Additionally, it might be considered to divide the obstetric APS into obstetric APS with early pregnancy complications and obstetric APS with late pregnancy complications. The division into two groups of obstetric APS might facilitate the choice of additional therapy in these women. PMID- 27395069 TI - Predictive factors for the appearance of myringosclerosis after myringotomy with ventilation tube placement: randomized study. AB - Myringotomy with the insertion of ventilation tubes is the most frequent surgical procedure performed in children, and the appearance of myringosclerosis is one of its most frequent long-term complications. The objective of this study is to identify clinical factors and technique variations that may have a relation with the appearance of myringosclerosis, after tube insertion. Patients submitted to myringotomy with transtympanic short-term tube insertion were studied in a longitudinal prospective and analytical cohort study with the prospective randomized open, blinded endpoint (PROBE) methodology, to study the influence of the location of myringotomy (anterior-inferior quadrant or posterior-inferior), directions of the incision (radial or non-radial) and aspiration or not of the middle ear. Our study included 156 patients (297 ears). Myringosclerosis was observed in 35.7 % of the operated ears. It appeared more often in patients with greater number of otitis (p = .001) and with greater number of otorrhea episodes (p = .029) and in patients in whom the tympanogram after the tube extraction was type A (according to Jerger's classification) (p = 0.016). We identified myringosclerosis in less patients, if the tube was in the tympanic membrane for less than 12 months (p = .009). Myringosclerosis was present more extensively if the tympanic incision was located in the anterior-inferior quadrant, with tympanic involvement superior to 25 % (p = .015). The results observed prove that, underlying the appearance of myringosclerosis, there exists an early inflammatory or infectious process and a final cicatricial process. It was also found that when myringotomy is made in the anterior-inferior quadrant, myringosclerosis appears in a higher percentage of the tympanic membrane; therefore, it is not recommended to do the incision in this quadrant, because it may lead to a reduction of the tympanic membrane vibration. PMID- 27395070 TI - Sex and age differences and outcomes in acute coronary syndromes. AB - BACKGROUND: There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (<=65years). METHODS: From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. RESULTS: The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2+/-6.6 vs. 54.1+/-7.4) and old (74.9+/ 6.4 vs. 73.6+/-6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. CONCLUSIONS: In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less. PMID- 27395071 TI - Irrigation water demand of selected agricultural crops in Germany between 1902 and 2010. AB - Irrigation water demand (IWD) is increasing worldwide, including in regions such as Germany that are characterized with low precipitation levels, yet grow water demanding crops such as sugar beets, potatoes, and vegetables. This study aimed to calculate and analyze the spatial and temporal changes in the IWD of four crops-spring barley, oat, winter wheat, and potato-between 1902 and 2010 in Germany by using the modeling software AgroHyd Farmmodel. Climatic conditions in Germany continued to change over the investigation period, with an increase in temperature of 0.01K/yr and an increase in precipitation of 1mm/yr. Nevertheless, no significant increasing or decreasing trend in IWD was noted in the analysis. The IWD for the investigated crops in the area of the current "Federal Republic of Germany" over the 109years was 112mm/yr, varying between 100 and 127mm/yr. Changes in cropping pattern and cultivated area over the last century caused large differences in the IWD calculated for each administrative district. The mean annual IWD of over the study period (which was divided into 4 parts) varied between 13,455Mm(3)/yr in the earliest period (1902-1919) and 4717Mm(3)/yr in the latest period (1990-2010). Policy and management measures to adapt to climate change are currently being debated in Germany. The presented results suggest that the effects of the choice of crops (in this case, changes in cropping pattern in the German nation states) had a stronger influence on regional water resources than those of climate variability. Thus, the influence of climate change on water resources is relativized which brings an important input into the debate. PMID- 27395072 TI - A novel bioaccessibility prediction method for PAHs in soil: Composite extraction with hydroxypropyl-beta-cyclodextrin and extracellular polymer substances. AB - Hydroxypropyl-beta-cyclodextrin (HPCD) extraction has been widely used to estimate bioaccessibility of polycyclic aromatic hydrocarbons (PAHs) in soil, but it often underestimates the actual risk due to lack of information regarding the exogenous active substances, such as extracellular polymer substance (EPS) secreted by microorganisms. In this study, a novel technique, composite extraction of HPCD each with rhamnolipid (RL), bovine serum albumin (BSA) and alginate sodium (AS), models of lipopolysaccharide, proteins and polysaccharides, was developed to assess PAHs bioaccessibility to earthworms. In addition, comparisons were conducted with accelerated solvent extraction (ASE) and individual HPCD extraction. The results demonstrated that all chemical extractions were linearly correlated with earthworm accumulation, and individual HPCD extraction underestimated PAH bioaccessibility by about two times. However, the overall performances of the three composite chemical extractions (HPCD/AS, HPCD/RL, HPCD/BSA) were better than individual HPCD extraction, among which, HPCD/AS was best at estimating the earthworm accumulation (considering both correlation coefficient and fitted linear slope). Therefore, all observations implied that HPCD/AS extraction could be used as a fast and reliable method to predict PAH bioaccessibility to earthworms in contaminated soils. PMID- 27395073 TI - Spatial and temporal distributions of Secchi depths and chlorophyll a concentrations in the Suo Nada of the Seto Inland Sea, Japan, exposed to anthropogenic nutrient loading. AB - Thirty years of monitoring data were used to elucidate the spatial and temporal distributions of Secchi depths in the Suo Nada (Suo Sea) and to evaluate how chlorophyll a concentration and reductions of nutrient loading from the watershed affected those distributions. Secchi depths throughout the Suo Nada were positively correlated with water depths. The spatial and temporal variations of Secchi depths could be explained by variations of phytoplankton biomass in areas where the water depth exceeded 20m, but in areas shallower than 10m, other factors affecting light attenuation beside phytoplankton, which include suspended particulate matter and chromophoric dissolved organic matter, obscured relationships between phytoplankton biomass and Secchi depths. Phosphorus limited phytoplankton biomass in the Suo Nada. The main source of allochthonous phosphorus from the 1980s to the 1990s was the watershed. Because of significant reductions of nutrient loading from the watershed, the Pacific Ocean will most likely be the principal source of allochthonous phosphorus after around 2000, except in areas shallower than 10m. PMID- 27395074 TI - Characterization of microbial community and antibiotic resistance genes in activated sludge under tetracycline and sulfamethoxazole selection pressure. AB - To investigate the microbial community characteristics, antibiotic resistance genes (ARGs), and bioreactor effluent quality change under tetracycline (TC) and sulfamethoxazole (SMX) selection pressure, sequencing batch reactors (SBRs) were used with environmentally relevant concentration and high-level of TC and SMX concentrations (0, 5ppb, 50ppb and 10ppm). Chemical oxygen demand (COD) and ammonia nitrogen (NH4(+)N) removals appeared unchanged (p>0.05) with 5 and 50ppb, but decreased significantly with 10ppm (p<0.05). Extracellular polymeric substances (EPS) concentrations increased significantly with increasing TC or SMX concentrations (p<0.05). High-throughput 16S rRNA gene sequencing results suggested that Proteobacteria, Actinobacteria and Bacteroidetes were the three most abundant phyla in sludge samples. The Actinobacteria percentages increased with increasing TC or SMX concentration, while Proteobacteria and Bacteroidetes decreased. The microbial diversity achieved its maximum at 5ppb and decreased with higher concentrations. The total ARGs abundances in sludge increased with addition of TC or SMX, and the higher relative abundances were in the order of sul1>tetG>sul2>tetA>intI1>tetS>tetC. Pearson correlation analysis showed most ARGs (tetA, tetC, tetG, tetK, tetM, sul1) were significantly correlated with intI1 (p<0.01). PMID- 27395075 TI - Presence and survival of culturable Campylobacter spp. and Escherichia coli in a temperate urban estuary. AB - Urban estuaries throughout the world typically contain elevated levels of faecal contamination, the extent of which is generally assessed using faecal indicator organisms (FIO) such as Escherichia coli. This study assesses whether the bacterial FIO, E. coli is a suitable surrogate for Campylobacter spp., in estuaries. The presence and survival dynamics of culturable E. coli and Campylobacter spp. are compared in the water column, bank sediments and bed sediments of the Yarra River estuary (located in Melbourne, Australia). The presence of E. coli did not necessarily indicate detectable levels of Campylobacter spp. in the water column, bed and bank sediments, but the inactivation rates of the two bacteria were similar in the water column. A key finding of the study is that E. coli and Campylobacter spp. can survive for up to 14days in the water column and up to 21days in the bed and bank sediments of the estuary. Preliminary data presented in this study also suggests that the inactivation rates of the two bacteria may be similar in bed and bank sediments. This undermines previous hypotheses that Campylobacter spp. cannot survive outside of its host and indicates that public health risks can persist in aquatic systems for up to three weeks after the initial contamination event. PMID- 27395076 TI - Empirical validation of the InVEST water yield ecosystem service model at a national scale. AB - A variety of tools have emerged with the goal of mapping the current delivery of ecosystem services and quantifying the impact of environmental changes. An important and often overlooked question is how accurate the outputs of these models are in relation to empirical observations. In this paper we validate a hydrological ecosystem service model (InVEST Water Yield Model) using widely available data. We modelled annual water yield in 22 UK catchments with widely varying land cover, population and geology, and compared model outputs with gauged river flow data from the UK National River Flow Archive. Values for input parameters were selected from existing literature to reflect conditions in the UK and were subjected to sensitivity analyses. We also compared model performance between precipitation and potential evapotranspiration data sourced from global- and UK-scale datasets. We then tested the transferability of the results within the UK by additional validation in a further 20 catchments. Whilst the model performed only moderately with global-scale data (linear regression of modelled total water yield against empirical data; slope=0.763, intercept=54.45, R(2)=0.963) with wide variation in performance between catchments, the model performed much better when using UK-scale input data, with closer fit to the observed data (slope=1.07, intercept=3.07, R(2)=0.990). With UK data the majority of catchments showed <10% difference between measured and modelled water yield but there was a minor but consistent overestimate per hectare (86m(3)/ha/year). Additional validation on a further 20 UK catchments was similarly robust, indicating that these results are transferable within the UK. These results suggest that relatively simple models can give accurate measures of ecosystem services. However, the choice of input data is critical and there is a need for further validation in other parts of the world. PMID- 27395077 TI - A comparison of metal concentrations in the tissues of yellow American eel (Anguilla rostrata) and European eel (Anguilla anguilla). AB - Historically abundant and widespread, populations of Atlantic eels have suffered a sharp decline in recent decades, in the ranges 40-80% and 90-99% for American and European eels, respectively. As a result, American eels are now classified as threatened, whereas European eels are considered to be in critical danger of extinction. Several causes have been identified as likely contributors of this decline, including overfishing, obstacles to migration (hydroelectric dams), climate change and habitat contamination. In the context of a larger project investigating the role of organic and inorganic contaminants in this decline, in this study, we measured the liver, kidney and muscle concentrations of essential (Cu, Se and Zn) and non-essential (Ag, As, Cd, Cr, Hg, Ni and Pb) metals in eels sampled at four sites in the South-West of France and four sites in Eastern Canada varying in contamination. Tissue concentrations of Cd, Hg and Se increased with fish size and age. Tissue metal concentrations generally reflected the contamination of their sampling sites. This was the case for Ag, As, Cd, Cu, Hg, Pb and Se. Comparison of tissue concentrations of these metals with the toxicological literature suggests that all of them except As could pose a risk to the health of eels from the most contaminated sites. In particular, European eels may be particularly at risk of Cd and Pb toxicity. Globally, our study suggests that a substantial accumulation of inorganic contaminants in the tissues of both eel species at sites contaminated by historical anthropogenic inputs may play a role in their decline. PMID- 27395078 TI - Solid-solution partitioning and thionation of diphenylarsinic acid in a flooded soil under the impact of sulfate and iron reduction. AB - Diphenylarsinic acid (DPAA) is a major organic arsenic (As) compound derived from abandoned chemical weapons. The solid-solution partitioning and transformation of DPAA in flooded soils are poorly understood but are of great concern. The identification of the mechanisms responsible for the mobilization and transformation of DPAA may help to develop effective remediation strategies. Here, soil and Fe mineral incubation experiments were carried out to elucidate the partitioning and transformation of DPAA in anoxic (without addition of sulfate or sodium lactate) and sulfide (with the addition of sulfate and sodium lactate) soil and to examine the impact of sulfate and Fe(III) reduction on these processes. Results show that DPAA was more effectively mobilized and thionated in sulfide soil than in anoxic soil. At the initial incubation stages (0-4weeks), 6.7-74.5% of the total DPAA in sulfide soil was mobilized likely by sorption competition with sodium lactate. At later incubation stage (4-8weeks), DPAA was almost completely released into the solution likely due to the near-complete Fe(III) reduction. Scanning transmission X-ray microscopy (STXM) results provide further direct evidence of elevated DPAA release coupled with Fe(III) reduction in sulfide environments. The total DPAA fraction decreased significantly to 24.5% after two weeks and reached 3.4% after eight weeks in sulfide soil, whereas no obvious elimination of DPAA occurred in anoxic soil at the initial two weeks and the total DPAA fraction decreased to 10.9% after eight weeks. This can be explained in part by the enhanced mobilization of DPAA and sulfate reduction in sulfide soil compared with anoxic soil. These results suggest that under flooded soil conditions, Fe(III) and sulfate reduction significantly promote DPAA mobilization and thionation, respectively, and we suggest that it is essential to consider both sulfate and Fe(III) reduction to further our understanding of the environmental fate of DPAA. PMID- 27395079 TI - Determination of micro-organic contaminants in groundwater (Maribor, Slovenia). AB - Micro-organic (MO) contaminants in groundwater can have adverse effects on both the environment and on human health. They enter the natural environment as a result of various processes, their presence in groundwater is the result of current anthropogenic activity and pollution loads from the past. A study on the occurrence and concentrations levels of selected contaminants in water was performed in the city of Maribor, Slovenia. A total of 56 groundwater and 4 surface water samples were collected in together four rounds in different hydrogeological periods (dry and wet seasons), and a total of 13 selected contaminants were analysed in this study. Carbamazepine, propyphenazone, caffeine, 2-methyl-2H-benzotriazole (2-MBT) and 2.4-dimethyl-2H-benzotriazole (2.4-DMBT) were determined as indicators of urban pollution, while pesticides and their metabolites (atrazine, desethylatrazine, deisopropylatrazine, terbuthylazine, desethylterbuthylazine, metolachlor, simazine, propazine) were mainly defined as indicators of crop production. All of the selected MO contaminants were detected both in the aquifer and Drava River. The most frequently detected MO compounds in groundwater were desethylatrazine (frequency of detection 98.2%; max. concentration 103.0ngL(-1)), atrazine (94.6%; 229ngL( 1)), 2.4-DMBT (92.9%; 273ngL(-1)), carbamazepine (80.4%; 88.00ngL(-1)), desethylterbuthylazine (76.8%; 7.0ngL(-1)) and simazine (76.8%; 29.6ngL(-1)), whereas propyphenazone (14.3%; 10.7ngL(-1)) was the least frequently detected. Detected MO concentrations in the study were compared with results published elsewhere around the world. Concentrations in groundwater indicate specific land use in their recharge areas. On the basis of correlations and the spatial distribution of selected MOs, groundwater origin for every sampling point was determined. Sampling sites were divided into three different groups for which indicative groundwater quality properties were defined. PMID- 27395080 TI - Mortality effects assessment of ambient PM2.5 pollution in the 74 leading cities of China. AB - BACKGROUND: Ambient fine particulate matter (PM2.5) pollution is currently a most severe and worrisome environmental problem in China. However, current knowledge of the health effects of this pollution is insufficient. OBJECTIVES: This study aims to provide an overall understanding regarding the long-term mortality effects of current PM2.5 pollution in China and the potential health benefits of realizing the goals stipulated in the ongoing action plan of Air Pollution Prevention and Control (APPC) and the targets suggested by the WHO. METHODS: Three typical causes and all-cause of PM2.5-related mortality were considered. The log-linear exposure-response function was adopted, and a meta-analysis was used to determine the exposure-response coefficients, based on newly available data in China and abroad. RESULTS: In the 74 leading cities of China, approximately 32% of the reported deaths, with a mortality rate of 1.90/00, were associated with PM2.5 in 2013, in which deaths from cardiovascular, respiratory and lung-cancer causes accounted for 20% of the reported deaths, with a mortality rate of 1.20/00. The regional difference is remarkable for the mortalities and proportions of the different causes. If the PM2.5 concentration goals of the APPC plan, the first interim and the guideline targets of the WHO could be achieved, the PM2.5-related all-cause mortality would be reduced by 25%, 64% and 95%, respectively, compared with that of 2013. CONCLUSIONS: PM2.5 pollution in China has incurred great health risks that are even worse than those of tobacco smoking. The health benefits of the APPC plan could be outstanding, although there is still great potential to improve future air quality. PMID- 27395081 TI - Impact of relative humidity on visibility degradation during a haze event: A case study. AB - Light scattering of aerosols depends on ambient relative humidity (RH) since hygroscopic particles absorb significant water at high RH, and this results in low visibility. This paper used custom-made parallel nephelometers (PNEPs) to measure aerosol light scattering enhancement factor f(RH), and utilized data including visibility, PM2.5, black carbon, water-soluble ions mass concentrations and surface meteorological parameters, in conjunction with background weather conditions, to analyze a haze event in Guangzhou during 8th-15th Dec. 2013. Unfavorable weather conditions, such as high RH and low wind speed, were observed during the haze event. The hourly average mass concentration of PM2.5 was 127MUg/m(3), with concentration of 192.4MUg/m(3) on 9th and 196MUg/m(3) on 13th. The f(RH) did not exhibit significant changes during this haze process, with value of f(80%)=1.58+/-0.07. Although the mass fraction of water-soluble ions to PM2.5 decreased after 12th Dec., the aerosol hygroscopicity might not have changed significantly since the mass fraction of nitrate became more dominant, which has stronger ability to take up water. The best-fitted parameterized function for f(RH) is f(RH)=0.731+0.1375*(1-RH/100)(-1)+0.00719*(1-RH/100)(-2). Combining the fixed parameterization of f(RH) above, the visibility was calculated with the measured light scattering and absorption coefficient of particles and gas under dry condition, as well as ambient RH. The predicted visibility range agrees well with the measurements without precipitation. Using ISORROPIA II model, the calculated aerosol liquid water content (ALWC) at ambient RH varied consistently with the PM2.5 under lower RH, while it was more influenced by high RH. This work also show that high RH accompanied with precipitation will enhance aerosol hygroscopic growth effect, leading to further visibility degradation, even if PM2.5 mass decreased due to precipitation. PMID- 27395082 TI - Sex Differences in the Biology and Pathology of the Aging Heart. AB - The knowledge that advanced age is a major risk factor for cardiovascular disease (CVD) has stimulated interest in cardiac aging. Understanding how the heart remodels with age can help us appreciate why older individuals are more likely to acquire heart disease. Growing evidence in both humans and animals shows that the heart exhibits distinct structural and functional changes as a consequence of age. These changes occur even in the absence of overt cardiovascular disease and are often maladaptive. For example, atrial hypertrophy and fibrosis may increase susceptibility to atrial fibrillation in older adults. Age-dependent increases in left ventricular fibrosis, stiffness, and wall thickness promote diastolic dysfunction, predisposing to heart failure with preserved ejection fraction. The influence of age on the heart is evident at rest but is even more prominent during exercise. There is also evidence for sex-specific variation in age associated remodelling. For instance, there is some evidence that the number of ventricular myocytes declines with age through apoptosis in men but not in women. This helps explain why older men are more likely than women to experience heart failure with reduced ejection fraction. Emerging evidence from preclinical studies suggests that frailty rather than chronological age promotes adverse cardiac remodelling. Mechanisms implicated in cardiac aging include impaired calcium handling, excessive activation of the beta-adrenergic and renin angiotensin systems, and mitochondrial dysfunction. Further research into cardiac aging in both sexes is needed, because it may be possible to modify disease treatment if the substrate upon which the disease first develops is better understood. PMID- 27395083 TI - Clinical value of non-HLA antibodies in kidney transplantation: Still an enigma? AB - HLA antibodies play a major role in the recipient's immune response against the renal allograft and are an established risk factor for antibody-mediated rejection and subsequent impaired graft survival. Evidence originating from HLA identical donor-recipient pairs indicates that non-HLA antibodies may play a role as well. Numerous non-HLA antibodies have been identified in renal organ transplantation, directed against a heterogeneous subset of both allo- and autoantigens including MHC Class-I-related chain A (MICA) and Angiotensin II type 1 receptor (AT1R). In this review, we will discuss the mechanisms predisposing to non-HLA antibody formation, the possible synergy with HLA-antibodies in their pathologic potential and the mechanisms involved in allograft damage. Furthermore, an overview of the identified non-HLA antibodies and antigens and their relation with rejection and graft survival will be provided. PMID- 27395084 TI - Categorization of endometritis and its association with ovarian follicular growth and ovulation, reproductive performance, dry matter intake, and milk yield in dairy cattle. AB - The objectives were to evaluate the effect of different categories of endometritis on follicular growth and ovulation, reproductive performance, dry matter intake (DMI), and milk yield (MY) in dairy cows. Lactating Holstein cows (n = 126) were examined for endometritis on 25 +/- 1 day postpartum (DPP) using vaginoscopy, transrectal ultrasonography, and endometrial cytology to determine the presence and type of vaginal discharge, uterine fluid, and proportion of polymorphonuclear (PMN) cells, respectively. Cows that had mucopurulent vaginal discharge and/or presence of uterine fluid, no mucopurulent vaginal discharge or uterine fluid but 8% or more PMN, and mucopurulent vaginal discharge and/or uterine fluid and 8% or more of PMN were defined as having clinical (CLIN; n = 45), cytological (CYTO; n = 15), and clinical and cytological (CLINCYTO; n = 30) endometritis, respectively. Cows that had none of the above pathological conditions were classified as unaffected (UNAF; n = 36). The diameter of the largest follicle at first examination, intervals from calving to first dominant (diameter = 10 mm) follicle, preovulatory size (diameter = 16 mm) follicle, ovulation, presence of follicular cyst, and proportion of ovular cows at 35 and 65 DPP were recorded as the measures of follicular growth and ovulation. None of the ovarian follicular parameters analyzed was affected by categories of endometritis. The first service conception rate tended (P = 0.06) to differ among categories of endometritis; cows that had CLIN and CLINCYTO endometritis were four times less likely to conceive to the first insemination compared to UNAF cows. Cows that had CLIN (hazard ratio: 0.52) and CLINCYTO (hazard ratio: 0.40) endometritis had decreased likelihood of pregnancy at 150 DPP compared to UNAF cows. Similarly, cows diagnosed as having CLINCYTO endometritis had decreased likelihood (hazard ratio: 0.48) of pregnancy at 250 DPP compared to UNAF cows. The DMI and MY up to 5 weeks postpartum were not affected by categories of endometritis. In summary, categories of endometritis as determined at 25 DPP did not affect follicular growth and ovulation, DMI, or MY. However, the combined (CLINCYTO endometritis) category had a negative impact on first service conception rate and subsequent services. PMID- 27395085 TI - Derivation and characterization of putative embryonic stem cells from cloned rabbit embryos. AB - The present study aimed to establish embryonic stem (ES) cell lines, i.e., ntES cells, using rabbit blastocyst stage embryos cloned by somatic cell nuclear transfer. First, we investigated the development of cloned rabbit embryos reconstructed with normal fibroblasts and fibroblasts transfected with enhanced green fluorescence protein (eGFP). Blastocyst rates were 27.4% and 23.9%, respectively, for the embryos reconstructed with normal fibroblasts and fibroblasts transfected with eGFP compared with that from the parthenogenetic group (43.1%). One ntES cell line was established from embryos reconstructed with eGFP-transfected fibroblasts (1 of 17, 5.9%), and three ntES cell lines were derived from those with normal fibroblasts (3 of 17, 17.6%). All the ntES cell lines retained alkaline phosphatase activity and expressed ES cell-specific markers SSEA-4, Oct-4, TRA-1-60, and TRA-1-81. The pluripotency was further confirmed by reverse transcription-polymerase chain reaction analyses of Oct-4, Nanog, and Sox-2 expressions in ntES cell lines. The differentiation capacity of ntES cells was also examined in vitro and in vivo, by which these ntES cell lines were able to differentiate into all three germ layers through embryoid bodies and teratomas. In conclusion, it is apparent that the efficiency of ntES cells derived using eGFP-transfected donor cells is lower than that with nontransfected, normal fibroblasts donor cells. Similar to those from parthenogenetic embryos, all ntES cell lines derived from cloned rabbit embryos are able to express pluripotency markers and retain their capability to differentiate into various cell lineages both in vitro and in vivo. PMID- 27395086 TI - Comparative morphology of immature stages of two sympatric Tenebrionidae species, with comments on their biology. AB - The mature larva and pupa of Neomida haemorrhoidalis are described and illustrated for the first time. The mature larva of Bolitophagus reticulatus is completely redescribed and illustrated, and its pupa is described for the first time. The differential diagnosis of the two species is presented. Information about their biology and life history is also given. PMID- 27395087 TI - An annotated catalogue of the gamasid mites associated with small mammals in Asiatic Russia. The family Laelapidae s. str. (Acari: Mesostigmata: Gamasina). AB - Twenty-nine species of mites of the family Laelapidae s. str. have been recorded as associated with small mammals (rodents, insectivores) in Asiatic Russia (Siberia and the Russian Far East). These species belong to two subfamilies (Laelapinae, Myonyssinae) and six genera: Androlaelaps Berlese, 1903, Dipolaelaps Zemskaya & Piontkovskaya, 1960, Laelaps C.L. Koch, 1836, Hyperlaelaps Zakhvatkin, 1948, Myonyssus Tiraboschi, 1904, Oryctolaelaps Lange, 1955. A list of the species, with data on synonymy, geographic ranges, and relationships with mammal hosts is provided. Some considerations concerning patterns of distribution of the parasitic Laelaptidae of Asiatic Russia are presented as well as their classifications from the point of view of known host association records. PMID- 27395088 TI - Pseudogramma polyacantha complex (Serranidae, tribe Grammistini): DNA barcoding results lead to the discovery of three cryptic species, including two new species from French Polynesia. AB - The Pseudogramma polyacantha species complex was found to harbor cryptic taxonomic diversity with three similar, but genetically divergent, species previously hidden in the complex. The true Pseudogramma polyacantha occurs from French Polynesia to South Africa and has modally 19 (many with 20) segmented dorsal-fin rays, modally 16 segmented anal-fin rays, a relatively short lateral line, no dermal flap or small tentacle dorsally on eye, and extensive scalation on the interorbital, suborbital and dentary. Pseudogramma brederi (previously synonymized with P. polyacantha) is recognized as a valid species occurring from Hawaii to Mauritius and having modally 21 segmented dorsal-fin rays, modally 17 segmented anal-fin rays, a relatively long lateral line, no dermal flap or small tentacle dorsally on eye, and relatively well-developed scalation on the interorbital, suborbital and dentary. Pseudogramma galzini n. sp. is described as a new species known only from French Polynesia and having modally 22 segmented dorsal-fin rays, modally 17 segmented anal-fin rays, a relatively long lateral line, no dermal flap or small tentacle dorsally on eye, and limited scalation on the interorbital, suborbital and dentary. Pseudogramma paucilepis n. sp. is described as a new species known only from French Polynesia and having 20 segmented dorsal-fin rays, modally 16 segmented anal-fin rays, a relatively long lateral line, no dermal flap or small tentacle dorsally on eye, and relatively reduced scalation on the interorbital, suborbital and dentary. A mtDNA COI analysis including all available Pseudogramma sequences shows well-supported genetic divergence between the two new species and among congeners. PMID- 27395089 TI - The taxonomy of Speodromia platyarthrodes (Stebbing, 1905) (Crustacea: Brachyura), an unusual dromiid crab endemic to South Africa. AB - The poorly known dromiid crab Speodromia platyarthrodes (Stebbing, 1905), endemic to South Africa, is redescribed and figured. Speodromia is unique among dromiids in possessing a large cavity on the anterior part of the sub-branchial region, which is believed to be associated with respiration. The systematics of the genus is discussed and is confirmed to be a member of Dromiinae De Haan, 1833, s. str. PMID- 27395090 TI - A new species and new records of Cryptodacus (Diptera: Tephritidae) from Colombia, Bolivia and Peru. AB - Cryptodacus bernardoi Rodriguez & Rodriguez, new species, is described from Colombia. It was reared from fruits of Phoradendron sp. near piperoides (Kunth) Trel. New distribution records are reported for Cryptodacus ornatus Norrbom from Colombia and Peru, for Cryptodacus trinotatus Norrbom & Korytkowski from Colombia, and for Cryptodacus obliquus Hendel from Bolivia and Peru. The female abdomen and terminalia of C. obliquus is described for the first time. The Norrbom & Korytkowski (2008)'s key to species was modified to include C. bernardoi n. sp. PMID- 27395091 TI - The third species of Meiyingia Holzschuh, 2010 (Coleoptera: Cerambycidae: Cerambycinae: Oemini) from China. AB - Meiyingia holzschuhi sp. nov. (Coleoptera: Cerambycidae: Cerambycinae: Oemini) is described from Guangxi Zhuang Autonomous Region, China. Important morphological characters of the new species are illustrated in color plates. A key to the three known species of the genus is modified to include the new species, and the known distribution of the genus is mapped. PMID- 27395092 TI - First report of Amynthas carnosus (Goto & Hatai, 1899) (Oligochaeta: Megascolecidae) in the Western Hemisphere. AB - The earthworm fauna of North America is still greatly unknown, with undescribed native species and new records of invasive species continually being discovered. The most recent checklists are difficult to reconcile, since they vary in their geographic coverage and taxonomy. Reynolds & Wetzel (2012) state that North America (including all of Mexico, some of the Caribbean, and Hawaii) is home for 256 species of earthworms, from which 188 are considered native or endemic and 68 are peregrine, exotic, and invasive species. Blakemore (2008) listed North America north of Mexico as having 183 earthworm species, of which 59 species are exotic. One Megascolecidae genus, Amynthas, is mostly located in the warmer subtropical and tropical regions of the world, with a few species that are able to survive the winter in the temperate zones of North America (Edwards & Bohlen 1995; Gorres et al. 2014). Here we report for the first time the occurrence of Amynthas carnosus (Goto & Hatai, 1899) in the United States. To our knowledge, this is not only the first report of A. carnosus in North America, but also its first report in the Western Hemisphere. The description below is intended to place our specimens in the correct taxon while avoiding future confusion with similar species, without making changes to the existing classification system. PMID- 27395093 TI - An annotated checklist of the Greek Stonefly Fauna (Insecta: Plecoptera). AB - An overview of the Greek stonefly (Plecoptera) fauna is presented as an annotated index of all available published records. These records have resulted in an updated species list reflecting current taxonomy and species distributions of the Greek peninsula and islands. Currently, a total of 71 species and seven subspecies belonging to seven families and 19 genera are reported from Greece. There is high species endemicity of the Leuctridae and Nemouridae, particularly on the Greek islands. The endemics known from Greece comprise thirty species representing 42% of the Greek stonefly fauna. The remaining taxa are typical Balkan and Mediterranean species. PMID- 27395094 TI - Taxonomic revision of the Afrotropical bee genus Serapista Cockerell (Hymenoptera: Apoidea: Megachilidae: Megachilinae: Anthidiini). AB - The Sub-Saharan bee genus Serapista Cockerell is revised. It comprises six species. Serapista pernigra Cockerell is restored as a valid species, S. aspernigra Eardley and Griswold, new species, is described from the eastern part of southern Africa and Serapista rhodesiana Mavromoustakis is synonymized with S. pernigra. Descriptions, keys for identification, distributional records and floral associations of the species of Serapista are given. PMID- 27395095 TI - More on the spider genus Xeropigo O.P.-Cambridge (Araneae, Corinnidae, Corinninae): seven new species and new records from Brazil. AB - Seven new species of the spider genus Xeropigo O. P.-Cambridge are described from Brazil, increasing the genus member list up to 16 species. X. piripiri n. sp., X. aitatu n. sp., and X. cajuina n. sp. are described from the state of Piaui. X. crispim n. sp. is described from the states of Ceara, Piaui, and Maranhao. X. oxente n. sp. is described from the state of Rio Grande do Norte. X. canga n. sp. is described from the state of Minas Gerais. X. ufo n. sp. is described from the state of Mato Grosso. The geographical distribution of X. tridentiger, X. camilae, X. pachitea, and X. perene is updated. A key to all species of Xeropigo is presented and possible relationships among all species of the genus are discussed. PMID- 27395097 TI - Two new species of the stenopodidean shrimp genus Spongiocaris Bruce & Baba, 1973 (Crustacea: Decapoda: Spongicolidae) from the Indo-West Pacific. AB - Two new species of the deep-water spongicolid genus Spongiocaris Bruce & Baba, 1973, are described and illustrated from two localities in the Indo-West Pacific. Spongiocaris panglao n. sp. is described on the basis of material from the Bohol Sea, the Philippines, at depths of 220-731 m. Spongiocaris tuerkayi n. sp. is described on the basis of material from Atlantis Bank in the southwestern Indian Ocean at depths of 743-1053 m. Among eight known congeners, both new species appear close to S. semiteres Bruce & Baba, 1973, differing in the rostral length and armature, shape of the carapace, telsonal armature, development of the grooming apparatus of the first pereopod and shape of the third pereopod chela. An identification key to the species currently assigned to Spongiocaris is presented. PMID- 27395096 TI - A review of genera and described Afrotropical species of Tetracampinae (Hymenoptera: Tetracampidae), with description of a new genus from East Central Africa. AB - The genera and described Afrotropical species of Tetracampinae Forster (Hymenoptera: Chalcidoidea, Tetracampidae) are reviewed. Despite the vague nature of some generic concepts, eight genera are recognized for the subfamily, i.e. Cassidocida Crawford, Diplesiostigma Girault, Dipriocampe Boucek, Epiclerus Haliday, Foersterella Dalla Torre, Niticampe Boucek, Tetracampe Forster, and the newly described Kilomotoia Gumovsky gen. n. The latter genus is established for Kilomotoia kitoko Gumovsky sp. n., collected from abandoned cultivated areas in the humid forest zone of North East Democratic Republic of Congo (Ituri forest, Ituri Province, environs of Mongbwalu village) and Central Uganda (Mabira forest, environs of Najembe village). Kilomotoia is distinguished from other tetracampine genera by the possession of a flattened dorsum, large abrupt pronotum, relatively long and laterally depressed gaster having gastral tergites II-V with medially emarginate posterior margins, and the hypopygium extending to the apex of gaster as sharply pointed mucro. The four hitherto described Afrotropical tetracampine species are reviewed based on available museum material, with Cassidocida africana Ferriere transferred to Foersterella as F. africana (Ferriere) comb. n., E. agromyzae (Risbec) and E. plectroniae (Risbec) confirmed as species of Epiclerus (as transferred earlier from Foersterella by Boucek 1958 and Boucek & Askew 1968), and Cassidocida orthopterae Risbec transferred to Closterocerus (Eulophidae, Entedoninae) as C. orthopterae (Risbec) comb. n. New diagnostic characters are proposed for the subfamily and some genera, and a comparative character table provided for tetracampine genera. PMID- 27395098 TI - Combining morphology, DNA sequences, and morphometrics: revising closely related species in the orb-weaving spider genus Araniella (Araneae, Araneidae). AB - The integration of independent data sets could solve problems in both traditional and DNA-based taxonomy. The aim of this study is to investigate the power of CO1 sequences and of morphometrics to distinguish closely related species in the spider genus Araniella. We put special emphasis on the species pair A. cucurbitina (Clerck, 1757) and A. opisthographa (Kulczynski, 1905) since the females are morphologically difficult to distinguish and often misidentified. A total of 216 sequences of eight Araniella species from seven European countries, North America and Asia were included in the molecular analysis. The results from both maximum likelihood and Bayesian phylogenetic inference indicate successful separation of six out of eight Araniella species, including A. cucurbitina and A. opisthographa. For the same six species, we detect no overlap of intra- and interspecific genetic divergence, leading to successful species identification with a threshold approach. In addition, morphometric analysis of the epigyna of A. cucurbitina and A. opisthographa supports species separation by two best explanatory ratios: receptaculum length and distance between receptaculum and copulatory duct. Although a small overlap in the ratios exists, the species identification rate increases when combining morphometric and molecular data, which demonstrates the efficiency of integrative approaches for distinguishing closely related species. However, none of the molecular approaches was able to separate closely related A. alpica (L. Koch, 1869) and A. inconspicua (Simon, 1874) due to shared CO1 haplotypes. Considering the clear morphological separation of the males and different habitat preferences, incomplete lineage sorting or introgressive hybridization could have led to identical CO1 sequences. Therefore, DNA-barcoding must be thoroughly tested even within small homogenous genera of spiders. PMID- 27395099 TI - A review of the genus Capulinia Signoret (Hemiptera: Coccoidea: Eriococcidae) with description of two new species. AB - The eriococcid genus Capulinia Signoret currently comprises four Neotropical species (the type species C. sallei Signoret, C. crateraformis Hempel, C. jaboticabae Ihering and an undescribed species recognised in the literature) and one species from New Zealand (C. orbiculata Hoy). All species feed on plants in the family Myrtaceae and the undescribed species is a pest of guava, Psidium guajava, in Venezuela and Colombia. Here we describe the pest species based on the adult female and first-instar nymph and name it Capulinia linarosae Kondo & Gullan sp. n. We provide a summary of published information on the biology and pest status of C. linarosae by translating the Spanish literature. We also describe the adult female and first-instar nymph of a new Argentine species that we name as C. luma Kondo & Gullan sp. n. after its host Luma apiculata. In addition, we redescribe the adult female of C. jaboticabae and include notes on C. crateraformis, C. orbiculata and C. sallei. We provide a revised generic diagnosis and keys to all Capulinia species based on adult females and, where available, first-instar nymphs, as well as a revised key to South American eriococcid genera. Phylogenetic analyses of 18S rDNA place Capulinia within the "Gondwanan" clade of eriococcids, mostly likely within the Myrtaceae-feeding group. PMID- 27395100 TI - Plesionika sanctaecatalinae Wicksten, 1983 (Crustacea Decapoda Caridea Pandalidae) from off the west coast of Pacific Mexico. AB - A large series of specimens of Plesionika sanctaecatalinae was obtained during sampling operations off the west coast of the Baja California Peninsula in 2012 and 2014 (TALUD cruises). This material was examined and compared to the original description, the holotype and two paratypes. Although the fresh material fit well with the type material examined, some discrepancies were noted in the illustrations of the original description, particularly regarding scaphocerite and the telson, and new illustrations are provided. The series of sample available from the TALUD cruises allow to increase considerably the number of localities known for this species in the California Current area. A series of unpublished records corresponding to material examined in the original description but not listed in details, allows for further increase of the number of reported localities where P. sanctaecatalinae has been collected. Its vertical distribution in the water column, however, remains unclear due to the fact that no discrete samples are available for this species. PMID- 27395101 TI - Revision of the Nearctic species of Callomyia Meigen (Diptera: Platypezidae) and phylogeny of the genus. AB - The Nearctic fauna of the genus Callomyia Meigen is revised and a phylogeny of the world species, based on morphological characters, is presented. Although morphological data are used primarily to delimit species, molecular sequence data (DNA barcodes) are used where possible, to help determine species boundaries and associate sexes. Species descriptions, diagnoses, and distribution maps are presented, along with illustrations of habitus, male terminalia, and additional important diagnostic characters. A key to the Nearctic species is provided. Ten species are recorded from the Nearctic Region including three new species: C. argentea Cumming sp. nov., C. arnaudi Cumming sp. nov., C. bertae Kessel, C. browni Cumming sp. nov., C. calla Kessel, C. corvina Kessel, C. gilloglyorum Kessel, C. proxima Johnson, C. velutina Johnson, and C. venusta Snow. The female of C. velutina is described, and three new synonyms are proposed: C. cleta Kessel is a junior synonym of C. calla syn. nov.; C. clara Kessel is a junior synonym of C. corvina syn. nov.; and C. liardia Kessel & Buegler is a junior synonym of C. proxima syn. nov. Phylogenetic relationships within the genus are reconstructed. The genus is monophyletic based primarily on the setulose R1 wing vein, female antennal size and three larval characters. The Nearctic species do not form a monophyletic group with respect to the Old World species. PMID- 27395102 TI - A new species of Polyipnus (Teleostei: Stomiiformes) from the western Pacific, with comments on the P. triphanos species complex. AB - A new species of the teleostean family Sternoptychidae, Polyipnus notatus n. sp., is described based on material collected mainly off Taiwan in the South China Sea. The new species is most similar to P. triphanos, based on the presence of a single posttemporal spine, lack of scale spination, and the second and third ACA (=supra-anal) photophores elevated relative to the first and connected to each other in a common organ. These characters typify other members of the P. asteroides species group that occur in various tropical to temperate ocean basins. Based on a limited sample of 27 specimens, P. notatus (maximum observed size 30.7 mm SL) appears to be smaller than most other congeners. It is also characterized by an unusual lateral pigment bar, which is narrow and distinctly triangular. Based on the material examined, the geographical distribution of the species appears to be restricted to the South China Sea and adjacent minor ocean basins. PMID- 27395103 TI - A new species of Trachytherus (Notoungulata: Mesotheriidae) from the late Oligocene (Deseadan) of Southern Peru and the middle latitude diversification of early diverging mesotheriids. AB - Herein we describe a new species of early diverging mesotheriid notoungulate from the late Oligocene of Moquegua, Peru. This taxon, Trachytherus ramirezi sp. nov., is distinctive in terms of a few characteristics that appear plesiomorphic as compared to those of other described mesotheriids, even other species referred to Trachytherus. Such plesiomorphic traits include the absence of an upper diastema and a lack of heart-shaped incisive foramina, traits that are generally present in other mesotheriids. Our phylogenetic analysis of described early divergent mesotheriids indicates that T. ramirezi was the earliest to diverge. This analysis also confirms the paraphyletic nature of the "genus" Trachytherus. Geographically, T. ramirezi clusters among T. alloxus, T. subandinus, and T. spegazzinianus, all of which are known from a discrete region in the middle latitudes of western South America that we refer to as the Bolivian Orocline Region (BOR). Our palaeobiogeographic reconstruction using maximum parsimony identifies the BOR as a possible ancestral area for the Mesotheriidae and as an important region for their diversification. For the more exclusive Mesotheriinae, the BOR was reconstructed as the ancestral area, an area from which some mesotheriines would have later dispersed to southern South America. Uncertainty concerning the ancestral area, for the Mesotheriidae-which could be BOR or southern South America area (or both)-is possibly due to the ignorance of the phylogenetic affinities for the undescribed mesotheriid remains reported from Tinguirirican localities. The present description of T. ramirezi therefore adds to the high taxonomic diversity of early mesotheriid species in the relatively small area of the BOR and emphasizes the likely role played by this topographically dynamic area on mesotheriid evolution during a significant time in the history of the clade. PMID- 27395104 TI - Two new species of the subgenus Cardiobioramix Kaszab (Coleoptera: Tenebrionidae: Bioramix Bates) from the Sichuan Province, China. AB - Two new species of darkling beetles (Tenebrionidae: Platyscelidini) belonging to the subgenus Cardiobioramix of the genus Bioramix are described. The first one, B. (C.) jinchuanensis sp. nov. known from the Chinese Province Sichuan Jinchuan, is characterized by the elongated parameres which are uniquely curved near the apex. The second one, B. (C.) maoxianensis sp. nov. described from Sichuan Maoxian and can be distinguished from the closely related B. (C.) szetschuana, B. (C.) kulzeri and B. (C.) subaenescens by the basally parallel parameres. A new identification key is provided to all known Chinese representatives of the subgenus Cardiobioramix. PMID- 27395105 TI - Istiochrysis gen. nov., a new chrysidid genus from Oriental China (Hymenoptera, Chrysididae). AB - Istiochrysis Rosa & Xu, gen. nov. (type species Istiochrysis ziliolii Rosa, Feng & Xu, sp. nov.) in the tribe Chrysidini is described from Oriental part of China (Yunnan). The new genus is related to the genera Caenochrysis Kimsey & Bohart, 1981, Chrysidea Bischoff, 1913, and Trichrysis Lichtenstein, 1876, but can be separated from them by the unique crestate structure of male genitalia, shape of black spots on sternum 2, and facial depressions on scapal basin. PMID- 27395106 TI - Erratum: LAKPA TAMANG, BIKRAMJIT SINHA & SHANTABALA DEVI GURUMAYUM (2015) Exostoma tenuicaudata, a new species of glyptosternine catfish (Siluriformes: Sisoridae) from the upper Brahmaputra drainage, northeastern India. Zootaxa, 4048(3): 441-445. PMID- 27395107 TI - Catalogue of the mite families Ascidae Voigts & Oudemans, Blattisociidae Garman and Melicharidae Hirschmann (Acari: Mesostigmata). AB - Until recently, mites in the families Ascidae, Blattisociidae and Melicharidae together constituted what was considered to be a single family, the Ascidae (sensu lato). We include all three families in this catalogue because of their many morphological similarities, as well as for historic and ecological reasons. Together with most Phytoseiidae and some Ameroseiidae, these are the only mesostigmatid mites commonly found on plants. In this publication we initially provide a historic overview of these groups, summarising the changes in the taxonomic concepts of the genera and other subfamilial taxa. This is followed by a thorough characterisation of each family and genus. A dichotomous key for the separation of families and genera is included. We then list the species considered to belong to these families, with details of the literature concerning the taxonomy of each species, and information about their type specimens and type localities wherever possible. The numbers of taxa considered as valid in this publication are: 372 species in 17 genera of Ascidae, 367 species in 14 genera of Blattisociidae, and 206 species in 11 genera of Melicharidae. We attempt to place each species in the most appropriate genus. In doing so, we propose 30 new combinations, including a species here transferred from Ascidae sensu stricto to Rhodacaridae. We propose five new names to replace junior homonyms, one new generic synonymy, and one new specific synonymy. Some species are insufficiently known and could not be reliably placed in any genus; these are listed as species incertae sedis. We also provide a list of species and genera that have been placed in these families at some time, but which have been transferred to other groups. PMID- 27395108 TI - A review of the subfamily Picobiinae Johnston and Kethley, 1973 (Acariformes: Prostigmata: Syringophilidae). AB - The fauna of quill mites of the subfamily Picobiinae Johnston and Kethley, 1973 (Acariformes: Cheyletoidea: Syringophilidae) is comprehensively revised. All of 78 known species, which are grouped into 11 genera, are examined and diagnosed or redescribed. Data on picobiine hosts and distribution are summarized, including new host and locality records. The following new species are described: Charadriineopicobia apricaria sp. nov. ex Pluvialis apricaria (Linnaeus) (Charadriiformes: Charadriidae) from France, Neopicobia pari sp. nov. ex Periparus venustulus Swinhoe (type host) (Passeriformes: Paridae) from China, Parus major Linnaeus (Paridae) from Macedonia and Finland, and Poecile varius Temminck and Schlegel (Paridae) from Japan, Picobia magellani sp. nov. ex Scytalopus magellanicus (Gmelin) (Passeriformes: Rhinocryptidae) from Colombia, Picobia lonchura sp. nov. ex Lonchura leucogastra (Blyth) (Passeriformes: Estrildidae) from Indonesia, Picobia makoli sp. nov. ex Xiphocolaptes promeropirhynchus (Lesson) (Passeriformes: Furnariidae) from Colombia. The species Picobia polonica Skoracki, Magowski and Dabert, 2001 syn. nov. is a junior synonym of C. khulkhaskhani Kivganov and Sharafat, 1995. The following new combinations are proposed: Neopicobia ictericus (Skoracki and Glowska, 2010) comb. nov., Rafapicobia brotogeris (Fain, Bochkov and Mironov, 2000) comb. nov., and Rafapicobia ramphastos (Fain, Bochkov and Mironov, 2000) comb. nov. Keys to the all picobiine genera and species are presented, along with a check-list of picobiine species and their hosts. PMID- 27395109 TI - Four new Schizopera (Copepoda, Harpacticoida) from marine interstitial habitats in Korea. AB - With more than 100 valid species, the predominantly marine genus Schizopera Sars, 1905 has a near global distribution. The genus is also relatively successful in invading estuarine and freshwater ecosystems. In Korea only two widely distributed estuarine species have been recorded previously: S. clandestina (Klie, 1924) and S. neglecta Akatova, 1935. Four rare new species discovered in marine interstitial habitats are reported herein. Schizopera daejinensis sp. nov. and S. yeonghaensis sp. nov. are described after a single female and one specimen of each sex respectively. These two species were found living simpatrically in Daejin beach, near Yeong Hae city, on the East Coast of Korea. The minute S. gangneungensis sp. nov. is described after three females from a beach in Gangneung city, also on the East Coast of Korea. Schizopera sindoensis sp. nov. is described after one female and five males from a tiny beach on Jeju Island, on the South Coast of Korea. Our detailed survey of Korean beaches and the absence of any of these species in other localities suggest them to be either short range endemics or anthropogenic relics. We discuss the need for further study and protection of these neglected habitats, and the role they might play in harbouring disproportionate levels of diversity. A variety of phenotypic features for comparative descriptions of the four new species were used, including all cuticular organs (sensilla and pores) on the somites. These minute and underutilized structures provide as much resolution on the species level as traditionally used characters do, with an added bonus of an almost complete lack of sexual dimorphism. This might provide useful directions for future pairing of opposite sexes in these and other copepods, especially in cases of sympatric congeners or missing sexes. PMID- 27395110 TI - True bugs (Hemiptera-Heteroptera) of Botswana-Bibliographical inventory and new records. AB - The knowledge of insect biodiversity of Botswana is far from perfect. By 2015, there were only inventories publicly available for butterflies, dragonflies and grasshoppers. Here we report 331 species and subspecies of true bugs (Heteroptera), of which 242 records were extracted from scattered published literature and online sources, and 89 (27%) are new records for Botswana. These data significantly increase the number of insect species known from Botswana by roughly 30%. PMID- 27395111 TI - Range extension for Eupiestus spinifer Fauvel in China (Coleoptera: Staphylinidae: Piestinae). AB - Eupiestus spinifer Fauvel, 1895 is newly recorded from China (Yunnan Province). The habitus and morphological details of this species are illustrated for the first time. PMID- 27395112 TI - Redescription of Gobio nigrescens from the Hari River drainage (Teleostei: Cyprinidae). AB - Gobio nigrescens, from the Hari River drainage, is redescribed. It represents a valid species distinguished from congeners in the adjacent Caspian and Aral Sea basins by a combination of characters: a naked breast, 16 circumpeduncular scales and 6-7 irregularly shaped, black or brown blotches on back behind dorsal-fin base. PMID- 27395113 TI - Dogielophis, a replacement name for Dogielina Sobolev 1950 (Nematoda) non Bogdanowicz & Woloszynova 1949 (Foraminifera). AB - The generic name Dogielina was proposed by Sobolev (in Skrjabin & al. 1950: 68; for Physaloptera inexpectata Dogiel & Bychowsky 1939: 93, type species by original designation) for a parasitic nematode of the fishes from the western shores of the Caspian Sea (Sara Island) of the former USSR (now Azerbaijan: Sari adasi, Nerimanabad). However, this name is already preoccupied by a fossil Foraminifera Dogielina Bogdanowicz & Woloszynova (1949: 185), published earlier in the same year (see note on publication dates below), which is in active current use in palaeontology and even served as a basis for a specific geological Dogielina sarmatica biozone in the Upper Miocene stratigraphy of Eurasia (Krezsek & Filipescu 2005). Besides this earliest generic name, a later homonym is also known in Protista: Dogielina Raabe (1959: 448) [Infusoria]. PMID- 27395114 TI - In BOLD we trust? A commentary on the reliability of specimen identification for DNA barcoding: a case study on burrower bugs (Hemiptera: Heteroptera: Cydnidae). AB - An assessment was performed regarding the accuracy of various types of data deposited in the Barcode of Life Data system (BOLD) related to the true bug family Cydnidae (Hemiptera: Heteroptera). Taxonomic nomenclature and classification, identification reliability, and the correctness of the data provided in the "Taxon description" were analyzed and commented on with respect to both available versions of the BOLD system, i.e. version 3 and beta version 4. Numerous mistakes in taxonomy, the relevance of the taxa names, and species misidentifications in BOLD version 3 were found and, more importantly, similar errors were detected in BOLD version 4 as well. We suggest that if the BOLD system is presumed to be taxonomically trustworthy, it can't exist without an adequate a priori identification of barcoded specimens. Otherwise, the erroneous data deposited onto the BOLD platform will have a negative impact on studies in which molecular data imported from BOLD are utilized. PMID- 27395115 TI - Notes on Bricelochlorops Paganelli 2002 (Diptera: Chloropidae), with the description of a new species. AB - Bricelochlorops is a peculiar genus of Chloropinae because its species possess a swollen pedicel and an enlarged clypeus separated into two parts. According to previous phylogenetic studies, Bricelochlorops is known as the sister group of Psilochlorops and their relationships with the remaining chloropine genera are unclear (Paganelli, 2002; Riccardi & Amorim, 2012). There are two described species of Bricelochlorops, B. peregrinus Paganelli 2002 and B. celutae Carvalho Filho & Esposito 2010. Both species are from Brazil and they are known only from the holotypes. Here, a further species from Peru is described, expanding the distribution of Bricelochlorops. PMID- 27395116 TI - Distribution of two species of Nephropsis Wood-Mason, 1872 (Crustacea, Decapoda, Nephropidae) from northeastern Brazil. AB - The genus Nephropsis Wood-Mason, 1872 has been reported from Brazil by Tavares (1998), Tavares & Young (2002), Silva et al. (2003), Dall'Occo et al. (2007) and Serejo et al. (2007), recording Nephropsis aculeata Smith, 1881, N. rosea Bate, 1888 and N. agassizii A. Milne-Edwards, 1880, the last of which occurs in both northeastern and southeastern of Brazil. PMID- 27395117 TI - A new subspecies of Xestia ashworthii (Doublebay, 1855) from Russian Altai (Lepidoptera, Noctuidae). AB - Xestia Hubner, [1818] is a large noctuine genus with an almost worldwide distribution. In the Palaearctic region the genus represented by about 190 described species (Kononenko 2003; Gyulai & Ronkay 2006; Fibiger et al. 2010; Gyulai et al. 2011; Kononenko et al. 2012; Gyulai et al. 2013a; 2013b). The genus subdivided into four described subgenera (Lafontaine et al. 1998, in Lafontaine 1998; Kononenko et al. 2012): Xestia, Megasema Hubner, [1821], Pachnobia Guenee, 1852 (= Schoyenia Aurivillius, 1883; Anomogyna Staudinger, 1871) and Raddea Alpheraky, 1892 (= Estimata I. Kozhanchikov, 1928; Erebophasma Boursin, 1963). Schoyenia and Anomogyna have been synonymised with Pachnobia by Lafontaine et al. (1998, in Lafontaine 1998). On the status of Raddea and synonymy of Estimata and Erebophasma see Lafontaine (1998). The genus is most diverse in the mountains of South Siberia, West China and the Himalayas. The Holarctic taxa of Pachnobia were revised by Mikkola et al. (1983, as Schoyenia), Lafontaine et al. (1987, as Pachnobia), and Lafontaine et al. (1998, in Lafontaine 1998); European taxa of the genus have been reviewed by Fibiger (1992; 1997), and the Nearctic fauna has been revised by Lafontaine (1998). The Asiatic fauna of the genus needs revision. PMID- 27395118 TI - The genus Tuponia Reuter, 1875 of China (Hemiptera: Heteroptera: Miridae: Phylinae: Exaeretini) with descriptions of three new species. AB - The species of Tuponia Reuter from China are reviewed. Three of them, T. gracilipedis, T. zhenyuanensis and T. virentis, are described as new. Tuponia ordosica Lu and Cui, 2011 is proposed as a synonym of T. arcufera Reuter, 1879. Keys to subgenera and Chinese species, and illustrations of the habitus and male genitalia for the recognized species are provided. Scanning electron micrographs are given for the new species. PMID- 27395119 TI - Description of two new species of annual fishes of the Hypsolebias antenori species group (Cyprinodontiformes: Rivulidae), from Northeast Brazil. AB - The Hypsolebias antenori species group comprises a monophyletic clade of annual fishes occurring in the semi-arid region of Northeastern Brazil. Most species of this group are found in the Rio Sao Francisco basin, but there are three species that inhabit small coastal basins. Hypsolebias faouri new species, is described from a temporary pool located near Rio Preto, a tributary of the Rio Sao Francisco, and Hypsolebias martinsi new species, is described from an annual pool near Rio Icaraizinho, a coastal drainage. Molecular data corroborates the monophyly of Hypsolebias and both new species. PMID- 27395120 TI - Holopothrips molzi sp.n. (Thysanoptera, Phlaeothripidae): natural history and interactions in Myrtaceae galls. AB - Holopothrips molzi sp. n. (Thysanoptera: Phlaeothripidae) is described from southern Brazil inducing leaf galls on Myrcia guianensis (Myrtaceae). Field observations revealed that the numbers of this thrips were highly variable within galls, and two other insect species were recorded living in these galls: Myrciathrips variabilis Cavalleri et al. (Phlaeothripidae) and an eulophid wasp (Hymenoptera). We investigated here if morphological traits of leaf and gall and abundance of the invader thrips were correlated with the gall inducer's abundance. In order to determine the feeding habit and behaviour of M. variabilis and its interactions with the gall inducer we performed observations ad libitum and attack simulation tests on both thrips species to observe their response to possible invaders. Our results showed that leaf size is not related to H. molzi abundance, and gall size is relevant only when total numbers of both thrips species are considered. Myrciathrips variabilis was observed feeding on gall tissues, and no direct antagonistic interactions between the two thrips were recorded. The results of the behavioural tests simulating attacks were remarkably different in the two thrips species, indicating different strategies when threatened or disturbed. The interaction between the two thrips species is probably a case of inquilinism. PMID- 27395121 TI - Taxonomic notes on three species of the genus Agonischius (Coleoptera, Elateridae, Elaterinae, Elaterini) with a new species from Taiwan. AB - Agonischius yokoyamai sp. nov. is described and represents the first record of Agonischius from Taiwan. This species resembles A. lateritius and A. insolitus, but is distinguished from the former by an orange body, yellowish-brown setae, longer antennae, and longer female sternite and tergite VIII, and from the latter by a wider body and differences in the male and female terminalia. Mouth-parts, abdominal terminalia and genitalia of this genus are described in detail and illustrated for the first time. These observations reveal that female sternite VIII and tergite VIII may be useful for species identification of Agonischius. PMID- 27395122 TI - A new genus of Asterocheridae (Copepoda: Siphonostomatoida) ectoassociate of the ascidian Eudistoma vannamei Millar, 1977 (Polycitoridae) from Brazil. AB - Asterocheres Boeck, 1860 is the largest genus of the siphonostomatoid copepod family Asterocheridae, containing 63 valid species. The genus is known for its symbiotic relationships with many marine invertebrate taxa, especially sponges, cnidarians, bryozoans, and echinoderms. Recent studies have restricted the diagnosis of this genus. Consequently, many species are now considered as species inquirendae. The present paper describes a new species living externally on the tunic of Eudistoma vannamei Millar, 1977, an endemic ascidian from Brazil. As the new species does not fit Asterocheres in the strict sense, a new genus is erected to accommodate it. Setacheres gen. nov. is characterized by its possession of two distal setae on the third endopodal segment of P3, thus differing from the distal seta and spine pattern that is deemed as diagnostic of Asterocheres. A revision and comparison of Asterocheres' species inquirendae revealed eight species sharing the same generic characteristics and were thus reallocated as members of the new genus. PMID- 27395123 TI - A new species of spiny-backed treefrog (Osteocephalus) from Central Amazonian Brazil (Amphibia: Anura: Hylidae). AB - A new species of treefrog of the genus Osteocephalus is described from the Rio Abacaxis, a southern tributary of the Amazonas in the state of Amazonas, Brazil. This member of the O. buckleyi group is characterized by green dorsal colouration with irregular blotches of various shades of brown, light venter with tan spots and bold dark markings on the posterior surfaces of the thighs. It can be distinguished from its closest relative, O. helenae from the same general area, by the lack of an axillary membrane, a few indistinct tubercles on the proximal segment of Finger IV and single ulnar tubercles. PMID- 27395124 TI - New records of the genus Parabolopona Matsumara (Hemiptera: Cicadellidae: Deltocephalinae), with description of a new species from India. AB - New records for the leafhopper genus Parabolopona Matsumura from India are provided with description of Parabolopona zhangi sp. nov. Materials are deposited in the National Pusa Collection, Division of Entomology, Indian Agricultural Research Institute (IARI), New Delhi, India. Morphological illustrations are provided. A checklist and key to species of the genus along with a distribution map are also provided. PMID- 27395125 TI - First record of Sonotrella Gorochov (Orthoptera: Gryllidae) from Laos, with description of a new species. AB - The genus Sonotrella Gorochov, 1988 is recorded to Laos for the first time. A new species is described and illustrated, S. (Sonotrella) laosensis sp. nov. (type locality: Laos). A distribution map of the species of Sonotrella (Sonotrella) and a key to the subgenera of Sonotrella worldwide are given. PMID- 27395126 TI - Euconnus malakkanus Franz transferred to Elacatophora Schaufuss (Coleoptera, Staphylinidae, Scydmaeninae). AB - The female holotype of Euconnus malakkanus Franz is recognized as belonging in Elacatophora Schaufuss; the species is transferred resulting in Elacatophora malakkana (Franz), comb. n. Although known only from a female, this species seems to be different from its morphologically uniform congeners, as demonstrated by comparing measurements and proportions of body parts. A checklist of all currently known species of Elacatophora with complete synonymy and distribution is provided. PMID- 27395127 TI - Ascidians (Tunicata) of the French Guiana Expedition. AB - Ascidians were collected along the shore of Iles du Salut and deeper on the slope in a program of evaluation of the biodiversity in Guiana. Most of the samples belong to already known species from the Caribbean area and Brazilian coast. The colonial forms dominate. The 6 new species have been dredged deeper than 50m but not found by SCUBA divers. In spite of an intensive sampling, the ascidian diversity in Guiana is low with 36 species recorded. This is the result of the abundance of sediment suspended in the water and uniformly deposited on all substrates which affects filtration rate and limits the settling of the ascidian larvae. PMID- 27395128 TI - A taxonomic revision of the Yasuni Round-eared bat, Lophostoma yasuni
(Chiroptera: Phyllostomidae). AB - The Yasuni Round-eared bat, Lophostoma yasuni, was described in 2004 by morphological analysis of the holotype, the only specimen attributed to this taxon to date. A molecular analysis using cytochrome-b sequences and a new morpholo-gical analysis that includes the holotype of L. yasuni and two specimens of L. carrikeri from near the type locality of L. yasuni were carried out. The new molecular and morphological evidence places L. yasuni within the clade of L. carrikeri. We propose that L. yasuni should therefore be considered as a synonym of L. carrikeri. An emended diagnosis for L. carrikeri extending ranges of craniodental measurements for this species is presented. PMID- 27395130 TI - Redescription of three cirolanid isopods (Crustacea: Peracarida) from Indonesia. AB - Three species of Cirolanidae described by Nierstrasz in 1931 are redescribed from the type material: Cirolana indica Nierstrasz, 1931, with new material from Singapore and Lombok Island, Indonesia; C. vanhoeffeni Nierstrasz, 1931; and C. stebbingi Nierstrasz, 1931, which is here transferred to the genus Politolana Bruce, 1981 based on the elongate body, long peduncle of pleopod 1, narrow and slender frontal lamina, flat and robust carpus of pereopod 7, long and acute robust setae on merus-propodus pereopod 1, secondary unguis on dactylus, and antenna peduncle articles 1-2 shorter than the subequal articles 3-5. PMID- 27395129 TI - Redescription of 13 holotypes of Rheocricotopus Brundin, 1956 (Diptera: Chironomidae) from the Sino-Indian Region. AB - Thirteen holotypes of the orthoclad genus Rheocricotopus from Sino-Indian Region: R. (Psilocricotopus) hidakadeeus Sasa & Suzuki, R. (P.) isigadeeus Sasa & Suzuki, R. (P.) kurocedeus Sasa, R. (P.) tokarakeleus Sasa & Suzuki, R. (P.) tobatervicesimus Kikuchi & Sasa, R. (Rheocricotopus) inaquereus Sasa, Kitami & Suzuki, R. (R.) inaxeyeus Sasa, Kitami & Suzuki, R. (R.) shoufukusecundus Sasa, R. (R.) tamahumeralis Sasa, R. (R.) tatequintus Sasa, R. (R.) tedorisecundus Sasa, R. (R.) togapeniculus Sasa & Okazawa and R. (R.) yakulemeus Sasa & Suzuki are re-examined and illustrated, Some additional descriptions, corrections and a key of these thirteen holotypes are given. PMID- 27395131 TI - Nephtyidae (Annelida: Polychaeta) from the Campos Basin, including two new species and a new record. AB - Members of the marine polychaete family Nephtyidae are commonly found in soft substrates. Their most distinctive characteristic is the presence of interramal branchiae located between the notopodia and neuropodia. In the present study, five species of Nephtyidae: Aglaophamus fabrun sp. nov., Aglaophamus juvenalis (Kinberg, 1866), Inermonephtys inermis (Ehlers, 1887), Inermonephtys soldius sp. nov. and Nephtys squamosa Ehlers, 1887 were found in the Campos Basin, state of Rio de Janeiro, including two new species and a new record for the Brazilian coast. Aglaophamus fabrun sp. nov. has a proboscis with 10 pairs of distal papillae and approximately 20 subdistal papillae in rows, with 3-5 papillae in each row; and lacks an unpaired median papilla; the prostomium has a pair of eyes and a characteristic pigmentation pattern. Inermonephtys soldius sp. nov. has interramal branchiae starting from parapodium 5, and basal papillae starting on chaetiger 6. Inermonephtys inermis is a new record for the Brazilian coast. Descriptions, comments and a key to species of Nephtyidae recorded from Brazil are provided. PMID- 27395132 TI - The genus Cecyrina Walker, 1867, with the description of two new species (Hemiptera: Pentatomidae: Asopinae). AB - In this paper, three species of the genus Cecyrina Walker are reported. Of these, the type species C. platyrhinoides Walker, 1867 is the only member of the genus previously recorded. Cecyrina flata sp. nov. and C. rubra sp. nov. are described as new to science. Illustrations of the male and female genitalic structures, the dorsal view of the head, the ventral view of the abdomen, and photographs of the adult dorsal and ventral habitus are provided. A key to the males of the genus is also provided to assist in future identification. The type specimens are deposited in the Institute of Entomology, Nankai University, Tianjin, China, except where noted. PMID- 27395133 TI - A new species of Idona DeLong (Hemiptera: Cicadellidae: Typhlocybinae)
from Mexico, with an annotated list of species. AB - A new dikraneurine leafhopper, Idona dmitrievi sp. nov., is described and illustrated from Mexico. An annotated checklist and a key for Mexican species are also provided. PMID- 27395134 TI - Neopetrosia de Laubenfels, 1949 from Brazil: description of a new species and a review of records (Haplosclerida: Demospongiae: Porifera). AB - The genus Neopetrosia was characterized by has fine brushes of oxeas issued from subectosomal tracts and compact choanosomal network. We report and describe here specimens collected in the coast of Brazil: Neopetrosia sulcata sp. nov. and Neopetrosia proxima. The first was previously recorded from Brazil as Neopetrosia proxima, but it was found that these specimens corresponded to a new species. Thus, we provide here the characterization of N. proxima from Brazilian coast. A taxonomic study of Brazilian samples is given, including description, illustrations and geographic distribution, combined with the comparison of the new species with all other descriptions of Neopetrosia from Atlantic. PMID- 27395135 TI - Microgomphus alani (Odonata, Gomphidae) sp. nov. from Cambodia. AB - Microgomphus alani sp. nov. is described from two males from the coastal southwestern foothills of the Cardamom Mts. in southwestern Cambodia (type locality: Cambodia, Koh Kong Province, 17 km ENE of Koh Kong, 'Macromia Rivulet', 11 degrees 40'17'' N, 103 degrees 07'28'' E, 296 m a.s.l., 3 vi 2014, RMNH). The species is characterised by its small size (hindwing 21-23 mm), cerci with outer angulations, truncated apices and crescent-shaped inner arms sprouting from their middle and not reaching their apices, synthorax with two parallel black lateral stripes and dorsal and collar yellow stripes fused in 7-like manner. Probably females of the same species were earlier reported from Phrae Province in northern Thailand. PMID- 27395136 TI - Investigating dental variation in Perameles nasuta Geoffroy, 1804, with morphological evidence to raise P. nasuta pallescens Thomas, 1923 to species rank. AB - The long-nosed bandicoot, Perameles nasuta Geoffroy, 1804, found on the east coast of Australia, has two subspecies, P. n. nasuta Geoffroy, 1804 and P. n. pallescens Thomas, 1923. Until recently, this distinction has remained untested by either morphological or molecular studies. Based on a recently published but limited molecular study, two publications have recommended that P. pallescens be treated as a species distinct from P. nasuta. Here, the morphological distinction between P. pallescens and P. nasuta is tested by examination of museum specimens from throughout the combined species range, using both qualitative and quantitative techniques. No external features and very few cranial features were found to separate the two subspecies. However, dental morphology and measurements are effective at distinguishing two geographically distinct populations; while a complex pattern of clinal vs non-clinal trends in cranial size suggest a genetic disjunction that corresponds with the dentally-defined geographic groups. These findings support the raising of P. pallescens to species level. In terms of dental features, P. pallescens was found to be most similar to the fossil P. sobbei. The morphological phylogeny recovered P. pallescens as sister to P. nasuta, when no fossil Perameles taxa were included, probably as a result of little cranial differentiation between them. When fossil Perameles were included, the relationships between species of Perameles were unresolved, probably as a result of P. sobbei lacking cranial remains. PMID- 27395137 TI - Taxonomy of the Caribbean sponge Dragmacidon reticulatum (Ridley & Dendy, 1886) (Porifera, Demospongiae, Axinellida), with the description of a new species. AB - Although there is a long history of taxonomic investigation in Caribbean sponges, there are still many undescribed species. Furthermore, field observations and corroborating morphological analyses are revealing that what was believed to be single, somewhat variable species, may consist of two or more species, often easier to distinguish once well characterized. This is the case for Dragmacidon reticulatum (Ridley & Dendy, 1886) (Porifera, Demospongiae, Axinellida, Axinellidae), a rather well-known sponge, with an ample distribution and presence in rocky and reef environments of the tropical and subtropical Western Atlantic, with local records in the majority of the countries of the area, from Bermuda to Brazil. Field observations and a detailed review of material from different areas, including some type specimens, led us to the distinction of two different species in terms of external morphology, size of spicules, and skeletal architecture. The distinction was confirmed in the Bahamas and Santa Marta, Colombia, where the two species coexist. One of the species is Dragmacidon reticulatum sensu stricto, but for the other there is need to erect a new name, for which we propose Dragmacidon alvarezae n. sp. The purpose of the present work is to describe, illustrate and compare these two species. PMID- 27395138 TI - Ahlbergia maoweiweii sp. n. from Shaanxi, China with revisional notes on similar species (Lepidoptera: Lycaenidae). AB - Ahlbergia maoweiweii sp. n. (Theclinae: Eumaeini) is described from Shaanxi, China. Ahlbergia frivaldszkyi, A. frivaldszkyi tricaudata, A. leei, A. confusa, A. ferrea and A. inopinata are reviewed. A. tricaudata stat. rev. (= A. frivaldszkyi tricaudata) is recognized as a separate species with A. tricaudata confusa stat. n. (= A. confusa) treated as its subspecies. Cornuti morphology of male genitalia is found to be diagnostic in taxonomy of the genus Ahlbergia. Other elfin butterflies externally similar to the new species are also discussed. New distributional data are given for A. clarolinea and A. chalcidis. Color photos of the type specimens of A. caesius and Novosatsuma magnapurpurea are given and a checklist of the Palaearctic elfin butterflies is updated. PMID- 27395139 TI - Description of a new species of the genus Hyalessa China (Hemiptera: Cicadidae: Sonatini) from Yunnan, China, with a key to the species of Hyalessa and a calling song analysis for two Hyalessa species. AB - A new species, Hyalessa scutata sp. nov., is described from Yunnan, China. This species is similar to Hyalessa fuscata (Distant, 1905) but is distinguished by the larger male opercula and the evenly narrow uncal lobe. Hyalessa ella (Lei & Chou, 1997) syn. nov. is synonymized with Hyalessa stratoria (Distant, 1905). A detailed sound analysis of the calling songs of Hyalessa fuscata (Distant, 1905) and Hyalessa maculaticollis (De Motschulsky, 1866) is provided. A key to the species of Hyalessa China, 1925 is also provided. A discussion is conducted for the first time about the presence of potential hybrids between H. maculaticollis and H. fuscata within Tsushima Island situated in the Korea Strait. PMID- 27395140 TI - A review of the genus Cyana Walker, 1854 (Lepidoptera, Erebidae, Arctiinae) from Cambodia, with description of new species. AB - Genus Cyana Walker, 1854, with 17 species in Cambodia, is reviewed. Among them, Cyana angkorensis Bayarsaikhan & Bae, sp. n. is described as new to science and 7 species are newly recorded from Cambodia. A key to the Cambodian species of the genus Cyana with illustrations of adults and genitalia is presented. PMID- 27395141 TI - Panonychus from Georgia: survey, taxonomical status and redescription of P. hadzhibejliae (Reck, 1947) (Acari, Tetranychidae). AB - A survey of Panonychus species was undertaken across Georgia from 2005 to 2014 on various host plants, revealing three species: Panonychus citri (McGregor, 1916), Panonychus hadzhibejliae (Reck, 1947) and Panonychus ulmi (Koch, 1836). New hosts for P. ulmi and P. citri are recorded, Buxus sempervirens, Hedera colchica and Prunus laurocerasus for P. ulmi and Ficus carica for P. citri, whereas P. hadzhibejliae was only found on F. carica. The newly collected material also allowed us to investigate the taxonomical status of P. hadzhibejliae. The comparison of P. hadzhibejliae with the two closely related species sampled in the survey, P. ulmi and P. citri, and with data of P. caricae found in the literature, shows that P. hadzhibejliae is a valid species. It can be separated from the three other Panonychus species without ambiguity especially using the female dorsal setae length in combination with the ratio between the length of the female dorsal opisthosomal f2 and h1 setae and the ratio between the palptarsal terminal eupathidium su and the related solenidion omega. A redescription of P. hadzhibejliae is provided including the male and some morphological characters, measurements and drawings of the female that were omitted in the original description. A key to the world species of Panonychus is also proposed. PMID- 27395142 TI - A new species of Epicriopsis Berlese (Acari: Mesostigmata: Ameroseiidae) from Brazil, with a key to the world species of the genus. AB - Epicriopsis atuberculatus n. sp. is described, based on the morphology of adult females and males collected from macauba palms (Acrocomia aculeata (Jacq.) Lodd. ex Mart.; Arecaceae) in Minas Gerais state, southeastern Brazil. This is the first species of the genus described from the American continent, from where it has been rarely reported. A key to the world species of Epicriopsis is provided. PMID- 27395144 TI - Two new species and nomenclatural changes in the Cis castaneus species group (Coleoptera, Ciidae). AB - Cis hanseni A. Strand, 1965 is a junior synonym of Cis matchanus Reitter, 1915 stat. nov. The lectotype for Cis matchanus Reitter, 1915 is designated and illustrated, together with its original data labels. Two new species-Cis lasoni sp. nov. and Cis lugowoji sp. nov. from the Talysh and Alborz Mts. (Azerbaijan, Iran)-are described. The body and terminalia of males are illustrated in detail. The definition of the Cis castaneus species group is discussed. PMID- 27395143 TI - First record of the family Sialidae (Megaloptera) from Thailand and description of the female and putative larva of Indosialis bannaensis. AB - Indosialis bannaensis is reported from northern Thailand marking the first record of the family, genus, and species from this country. The female and the probable larva of the species are described for the first time. PMID- 27395145 TI - New genera, new species and redescriptions of Australian jumping spiders
(Araneae: Salticidae). AB - A number of Australian species have been placed in the wrong, often non Australian, genera. Some of these problems have been corrected here, by transfer or establishment of new genera. Several new species discovered during the course of the work are also described. Marptusa jovialis L. Koch, 1879 and Marptusa bracteata L. Koch, 1879 are transferred to Apricia gen. nov. Apricia longipalpis sp. nov. is also described from Australia. The study of the Australian species presently included in Trite Simon 1885 showed that this genus does not occur in mainland Australia. Hence, Marptusa vulpecula Thorell, 1881 is transferred to Capeyorkia gen. nov., while Marptusa longula Thorell, 1881 is transferred to Evarcha Simon, 1902. The only previously described 'Australian' species to remain in Trite is Trite concinna Rainbow, 1920, from Lord Howe Island and Norfolk Island in the Pacific, while Trite grayi sp. nov., also from Lord Howe Island, is described here. Trite concinna Rainbow 1920 is redescribed. Most specimens previous listed as this species from Lord Howe Island (including most of the syntype series) belong in Ancepitilobus howensis gen. nov. et sp. nov. Clynotis severus (L. Koch, 1879) is the solitary species that remains in Clynotis Simon, 1901, with the remainder of the mainland species being transferred to Pungalina Richardson, 2013: P. albobarbata (L. Koch, 1879) comb. nov., P. semiatra (L. Koch, 1879) comb. nov. and P. semiferruginea (L. Koch, 1879) comb. nov. Pungalina plurilineata sp. nov. and Pungalina waldockae sp. nov. are also described from Australia. Clynotis gratiosa from Lord Howe Island is formally transferred to Tara Peckham & Peckham, 1886, as suggested previously. Tara gratiosa (Rainbow, 1920) is redescribed. Finally, three names, Gangus longulus Simon, 1902, Trite ornata Rainbow, 1915 and Plexippus albopilosus Keyserling, 1883, are considered species inquirendae, due to the state or loss of type material. PMID- 27395146 TI - Revision of Japanese species of the genus Ecnomus McLachlan (Trichoptera: Ecnomidae), with descriptions of two new species. AB - Five species of the genus Ecnomus McLachlan (Ecnomidae), including 2 new species, are recognized from Japan: E. hokkaidensis sp. nov. from Hokkaido and E. sakishimensis sp. nov. from Ishigaki-jima and Iriomote-jima, Ryukyu Islands, are described. Ecnomus japonicus Fischer, originally described from Kyushu, is re described. In addition, illustrations of the male and female genitalia are provided for E. tenellus (Rambur) and E. yamashironis Tsuda, which are common species in Japan. Ecnomus kososiensis Kobayashi, originally described from Honshu, and E. tsudai Kumanski, originally described from Korea, are synonymized under E. tenellus and E. japonicus, respectively. PMID- 27395147 TI - First records of Chevrolatiini and Cephenniini in Eocene Baltic amber (Coleoptera, Staphylinidae, Scydmaeninae). AB - Fossils of two tribes of the ant-like stone beetles, previously unknown in Eocene deposits, are recorded, based on inclusions in Baltic amber. Well-preserved specimens of Chevrolatia sp. (Chevrolatiini) and Cephennodes sp. (Cephenniini) are described, but the species lack reliable diagnostic characters and remain unnamed. This is the first record of a fossil of Chevrolatiini, an extant tribe that includes only one genus, Chevrolatia Jacquelin du Val, distributed in the Holarctic, Mexico, West Palaearctic and Afrotropical regions. The extant tribe Cephenniini, in turn, is cosmopolitan, but the only fossil unambiguously assigned to this taxon, an unnamed genus, was known from Upper Cretaceous Burmese amber. Many extant species of Cephennodes Reitter are known from Palaearctic, but they predominantly inhabit its eastern part, with only two species occurring in Europe. The Eocene specimen of Cephennodes sp. is also the first known fossil of this genus. PMID- 27395148 TI - Kuznetsovia, a new generic replacement name for Aenigma Kuznetsova, 1957 (Ostracoda) non Newman, 1836 (Coleoptera). AB - The generic name Aenigma was proposed by Kuznetsova (1957: 68; type species A. jucunda Kuznetsova, by original designation) for a new fossil ostracod genus from the Lower Cretaceous (Barremian) of Tegchaj, North-Eastern Azerbaijan, former USSR (Transcaucasia). However, this name is already preoccupied by a marine gastropod molluscan generic name Aenigma Newman (1836: 499), which is in active current use in zoology (Coleoptera: Carabidae). Besides this earliest generic name, a few homonyms were also known: Aenigma Amsel (1956: 288) [Lepidoptera], Aenigma Koch (in Martin & Chemnitz 1846: 1, unpaginated) [Mollusca], Aenigma Karsch (1878: 825) [Arachnida], Aenigma Strecker (1876: 122) [Lepidoptera]. PMID- 27395149 TI - A new genus and species of micro bee fly from the Earliest Eocene French amber (Diptera: Mythicomyiidae: Psiloderoidinae). AB - Mythicomyiidae, or micro bee flies, are tiny flies (0.5-5.0 mm) that are found throughout most parts of the world except the highest altitudes and latitudes (Greathead & Evenhuis 2001). Including all extinct and extant taxa, the Mythicomyiidae currently comprise more than 380 valid taxonomic species distributed among 30 genera. The subfamily Psiloderoidinae is especially well represented among the fossil Mythicomyiidae by seven Cretaceous or Cenozoic genera. We here describe a new genus and a new species of this subfamily based on fossils from the Earliest Eocene of Oise (France). A Psiloderoidinae, Proplatypygus matilei Nel & DePloeg, 2004, is already described in this amber. Another mythicomyiid, Eurodoliopteryx inexpectatus Nel, 2006, is the most frequent bombylioid in this amber (Nel & DePloeg, 2004; Nel, 2006). PMID- 27395150 TI - A note on the correct spelling of the name of the freshwater shrimp Macrobrachium olfersii (Wiegmann, 1836) (Decapoda, Palaemonidae). AB - Macrobrachium olfersii (Wiegmann, 1836), popularly known as Pitu, Bristled River Shrimp and Buchura River Prawn, is a freshwater shrimp species widespread along the eastern coasts of the Americas. The species can be found from the southeastern United States, where the prawns were introduced (Holthuis & Provenzano, 1970), southwards to Rio Grande do Sul (Brazil), including numerous records in Mexico, Nicaragua, Costa Rica, Panama, Colombia, Venezuela, Guyana and Suriname (Holthuis, 1952; Williams, 1984; Melo, 2003; Valencia & Campos, 2007). PMID- 27395151 TI - A new Anagyrus (Hymenoptera: Encyrtidae) from Argentina, parasitoid of Hypogeococcus sp. (Hemiptera: Pseudococcidae) on Harrisia pomanensis (Cactaceae). AB - A new species of Anagyrus Howard (Hymenoptera: Encyrtidae), A. lapachosus sp. n., is described from Salta Province of Argentina as a parasitoid of Hypogeococcus sp. (Hemiptera: Pseudococcidae) on Harrisia pomanensis cactus (Cactaceae). It is a candidate "new association" biological control agent for quarantine evaluation and possible following introduction to Puerto Rico (USA) against another Hypogeococcus sp., commonly called the Harrisia cactus mealybug and often misidentified as H. pungens Granara de Willink (according to our unpublished data the latter attacks only Amaranthaceae), which devastates or threatens the native cacti there and also in some other Caribbean islands (Triapitsyn, Aguirre et al. 2014; Carrera-Martinez et al. 2015). PMID- 27395152 TI - Geraldocossus gen. nov. (Lepidoptera, Cossidae) from Mount Cameroon (West Africa). AB - The cossid or the Carpenter Moths (Lepidoptera, Cossidae) include about 1000 species worldwide (van Nieukerken et al., 2011), of which 750 species belong to five subfamilies that occur in the Old World (Yakovlev 2011). The Cossidae are still relatively poorly known from vast areas of the African continent, despite recent reports on the fauna of Malawi (Yakovlev & Murphey 2014), Zimbabwe (Yakovlev & Lenz 2014), and Zambia (Yakovlev 2014). The first results of an ongoing revision of the South African Cossidae have also been published (Mey 2015). PMID- 27395153 TI - Erratum: ALEXEY V. SHAVRIN (2016) A review of the genus Pycnoglypta Thomson, 1858 (Staphylinidae, Omaliinae, Omaliini) with notes on related taxa. Zootaxa, 4077(1): 001-094. PMID- 27395154 TI - New genera, species and records of Maeridae from Australian Waters:
Austromaera, Ceradocus, Glossomaera, Hamimaera, Huonella gen. nov.,
Linguimaera and Maeraceterus gen. nov. (Crustacea: Amphipoda). AB - Thirty species of Maeridae are reported for Australian waters including the description of two new genera and nine new species. The new genus Huonella from southern Tasmanian seamounts is distinguished among the maerids by characters on the uropod 3, including elongation of both rami, inner ramus half the length of the outer ramus and outer ramus two articulate. The new genus Maeraceterus is establish for two new species, M. bramblensis from Western Australia and M. taaroa from Norfolk Island, which have a near transverse gnathopod 1 propodus palm and symmetrical male gnathopod 2. The new species Ceradocus baudini, Hamimaera thijsseni, Linguimaera boeckoides, L. daveyi, L. everardensis and L. mere are described here in. Additional distribution records are provided for eleven known Ceradocus and seven known Linguimaera, as well as three known maerids Austromaera mastersii (Haswell, 1879a), Glossomaera octodens (Sivaprakasam, 1969) and Hamimaera hamigera (Haswell, 1879b). Collections reported on here include material from Australia; Cocos (Keeling) and Christmas Islands, Indian Ocean; the Torres Strait; Papua New Guinea, Bismarck Sea and Norfolk Island, South Pacific. Keys to Ceradocus and Linguimaera sensu lato species in Australian waters are provided. PMID- 27395155 TI - Revision of Ephydrini Zetterstedt (Diptera: Ephydridae) from the Americas south of the United States. AB - The Neotropical genera and species of the tribe Ephydrini are revised and include nine genera and 33 species. Of the nine genera, Setacera Cresson, Cirrula Cresson, Dimecoenia Cresson, Paracoenia Cresson and Ephydra Fallen are mostly temperate in distribution, primarily in the Northern Hemisphere. The other four genera, which are exclusively Neotropical, include two, Austrocoenia and Notiocoenia, that were treated previously in the tribe Scatellini, and two recently described genera: Paraephydra (type species: Paraephydra freitasi (Oliveira)) and Neoephydra (type species: Neoephydra araucaria Mathis). New species described herein are: Neoephydra neotropica (Chile), N. dasycephala (Argentina and Peru), N. mallonota (Argentina, Bolivia, and Chile), N. shewelli (Argentina, Bolivia, and Chile), N. inca (Argentina, Bolivia, Peru), N. penai (Chile) and N. trichina (Argentina and Chile). New synonyms are (cited in their original combinations): Ephydra densepilosa Hendel = E. ciligena Rondani, Dimecoenia grumanni Oliveira = E. ciligena Rondani, D. coltaensis Cresson = D. zurcheri Hendel, D. carrerai Oliveira = D. zurcheri Hendel, D. lopesi = E. ciligena Rondani, D. travassosi Mello and Oliveira = E. prionoptera Thomson. A neotype is designated for E. caesia Wulp, and the following lectotype designations have also been made to better stabilize nomenclature (here cited in their original combination): Ephydra chilensis Macquart, Ephydra densepilosa Hendel, Ephydra pravoneura Hendel, Ephydra prionoptera Thomson, and Dimecoenia zurcheri Hendel. Dimecoenia venteli Oliveira is listed as a species inquirenda, as the type series includes only female specimens that we cannot presently recognize. Although the genera and subgenera are fairly easily distinguished, the included species are frequently difficult to separate, and we have generally relied on characters of the male terminalia to determine a species identity. Illustrations of male terminalia and distribution maps are included for each species and keys to all taxa have been provided. PMID- 27395157 TI - Biology and immature stages of Pherbellia limbata (Diptera: Sciomyzidae), a parasitoid of the terrestrial snail Granaria frumentum. AB - The very rare Palaearctic Pherbellia limbata (Meigen, 1830) lives in limestone steppes and other xerothermic habitats in central and southern Europe. For the first time, the egg, first-, second- and third-instar larvae and the puparium are described. Scanning electron micrographs of various morphological features of immature stages are provided. Larvae of P. limbata are parasitoids exclusively of the terrestrial snail Granaria frumentum (Draparnaud, 1801). Results of this study are integrated with those of previous studies of the biology, ecology, immature stages, and mollusc-prey habitat of the other 28 (of 96) Pherbellia species for which life cycles have been completely or partially elucidated. Recent published taxonomic approaches to clarifying the phylogeny of the Sciomyzidae are discussed, particularly those involving DNA analyses of Pherbellia species. PMID- 27395156 TI - Contribution to the knowledge of Stenochironomus Kieffer (Diptera, Chironomidae) from Brazil: seven new species and description of females and immatures of some previously known species. AB - Twenty two species of Stenochironomus Kieffer are known from Brazil, 19 of which occur in the Amazon region. In order to increase knowledge of the taxonomy of this genus in the Amazon region, collections were carried out in streams located in Presidente Figueiredo, Manaus and Itacoatiara municipalities, Amazonas State. Leaves and wood mined by Stenochironomus larvae were collected and transported to the laboratory where they were kept until adult emergence. Seven new species were found, one of which is described in the immature stages and as adults of both sexes (S. amazonicus sp. n.), one as immatures and adult male (S. liviae sp. n.), four as male and pupa (S. bare sp. n., S. figueiredoensis sp. n., S. gracilis sp. nov. and S. manauara sp. n.) and one only as male (S. suzanae sp. n.). Additionally, the female, pupa and larva of S. impendens Borkent, pupa and larva of S. jubatus Borkent, female and pupa of S. zonarius Borkent and female of S. palliaculeatus Borkent were described. PMID- 27395158 TI - Seven new species of the earthworm genus Metaphire Sims & Easton, 1972 from Thailand (Clitellata: Megascolecidae). AB - Earthworm specimens collected from various parts of Thailand were found to contain seven new species of the genus Metaphire Sims & Easton, 1972. These are M. songkhlaensis sp. n. in the octothecal pulauensis species group, M. trangensis sp. n. in the octothecal ignobilis species group, M. khaoluangensis sp. n. and M. khaochamao sp. n. in the sexthecal houlleti species group, M. doiphamon sp. n. in the sexthecal peguana species group, M. saxicalcis sp. n. in the quadrithecal planata species group, and the bithecal M. surinensis sp. n. Type material of some established species from Thailand or northern Malaysia was reinvestigated and illustrated to confirm the status of the new species and to facilitate species comparisons: M. pulauensis (Beddard, 1900), M. baruana (Stephenson, 1932), both with newly designated lectotypes, and M. planata (Gates, 1936), illustrated and redescribed. PMID- 27395159 TI - A new pupillarial scale insect (Hemiptera: Coccoidea: Eriococcidae) from Angophora in coastal New South Wales, Australia. AB - A new scale insect, Aolacoccus angophorae gen. nov. and sp. nov. (Eriococcidae), is described from the bark of Angophora (Myrtaceae) growing in the Sydney area of New South Wales, Australia. These insects do not produce honeydew, are not ant tended and probably feed on cortical parenchyma. The adult female is pupillarial as it is retained within the cuticle of the penultimate (second) instar. The crawlers (mobile first-instar nymphs) emerge via a flap or operculum at the posterior end of the abdomen of the second-instar exuviae. The adult and second instar females, second-instar male and first-instar nymph, as well as salient features of the apterous adult male, are described and illustrated. The adult female of this new taxon has some morphological similarities to females of the non-pupillarial palm scale Phoenicococcus marlatti Cockerell (Phoenicococcidae), the pupillarial palm scales (Halimococcidae) and some pupillarial genera of armoured scales (Diaspididae), but is related to other Australian Myrtaceae feeding eriococcids. PMID- 27395160 TI - Review of the genus Stenothemus Bourgeois from Taiwan, with description of three new species (Coleoptera: Cantharidae) and additional distributional records of previously known species. AB - The genus Stenothemus Bourgeois from Taiwan is reviewed, with description of three new species: S. lupus sp. nov., S. gemini sp. nov. and S. vulpecula sp. nov. Each species is described with photos of habitus, and the new species also include illustrations of aedeagi, female genitalia and abdominal ventrite VII (= sternite VIII) of female if available. In addition, the female of S. mamorui Okushima & M. Sato, 1999 is described for the first time, and female genitalia and the abdominal ventrite VII are illustrated. A distribution map of Stenothemus from Taiwan is presented, and an updated key for the identification of Stenothemus species from Taiwan is given. PMID- 27395161 TI - Revision of the genus Pollux (Acari: Erythraeidae) and redescription of P. kovalamicus. AB - Pollux kovalamicus Haitlinger, 2002 is redescribed based on the holotype and three additional specimens (larvae) collected from Iran (Sistan and Baluchistan Province) and Pakistan. It is the first report of the genus from Iran. The following character states from the original description are corrected: scutum and scutalae AL and PL present, ML absent, 4n setae on BFe I (3 in original description), microseta on Ge I and II and Ti I present (absent in original description); companion seta (z) and famulus on Ta I and II present (absent in original description). Pollux walii Kamran et al., 2010 is herein considered to be a junior synonym of P. kovalamicus. A key to the world species of Pollux is given. PMID- 27395162 TI - Lysippe nikiti sp. nov. (Polychaeta, Terebellomorpha) from the deep Pacific and Indian Oceans with an amendment to the generic diagnosis of Lysippe. AB - Lysippe nikiti n. sp. is described from abyssal depths in the North Pacific and Indian Oceans. It differs from other species of the genus in that it has 14 thoracic uncinigers, ten abdominal uncinigers and three pairs of branchiae. The generic diagnosis is emended to include the newly described fully retractable nuchal organs of the type species L. labiata and details of the position of the nephridiopores. The validity of Samytha is discussed and it is proposed that this genus be treated as junior synonym of Lysippe. Of the 22 species described as Lysippe or its junior synonyms, eight: L. agulhasensis, L. capensis, L. vanelli type species of Eclysippe, Samytha bioculata-type species of Mooresamytha, S. (?) heterobranchia, S. oculata, S. pallescens-type species of Glyphanostomum and S. (?) speculatrix-have been or should, for reasons discussed here, be transferred to other genera. Neither the original description nor later redescriptions allow differentiation of Samytha californiensis from L. gurjanovae. Thus Lysippe currently includes 13 valid species: L. annectens-type species of Paralysippe, L. annenkovae, L. caeca, L. fragilis-type species of Lysippides, L. gurjanovae, L. hesslei, L. labiata, L. mexicana-type species of Pseudampharete, L. nikiti, L. nipponica, L. sexcirrata, L. storchi and L. trichobranchia. PMID- 27395163 TI - A new Agraecina spider species from the Balkan Peninsula (FYR Macedonia) (Araneae: Liocranidae). AB - Specimens were collected using pitfall traps. Coloration is described from alcohol-preserved specimens. Specimens were examined and measured using a Wild M5A stereomicroscope. Further details were studied and measured under an Olympus BX41 compound microscope. All drawings were made using a drawing apparatus attached to a Leica stereomicroscope. Male palps and female genitalia were examined and illustrated after they were dissected from the spiders' bodies. Photos were taken with an Olympus C7070 wide zoom digital camera mounted on an Olympus SZX12 stereomicroscope. The images were montaged using Helicon Focus image stacking software. Measurements of the legs are taken from the dorsal side. Total length of the body includes the chelicerae. All measurements were taken in mm. Abbreviations used in text include: AME, anterior median eyes; ALE, anterior lateral eyes; EM, embolus; MA, median apophysis; CD, copulatory duct; ST, spermatheca; fe, femur; pa, patella; ti, tibia; mt, metatarsus; p, prolateral; d, dorsal; r, retrolateral; v, ventral. Type specimens are deposited in the National Museum of Natural History (NMNHS), Sofia, Bulgaria. PMID- 27395164 TI - Transfer of the assassin bug Nitornus fuliginosus to the genus Apronius
(Hemiptera: Heteroptera: Reduviidae: Stenopodainae). AB - Based on examination of its lectotype (here designated), the assassin bug Nitornus fuliginosus Distant, 1902 (Hemiptera: Heteroptera: Reduviidae: Stenopodainae) is transferred to the genus Apronius Stal, 1865, with the resulting new combination: Apronius fuliginosus (Distant, 1902), comb. nov. PMID- 27395165 TI - A new species of Apterichtus (Anguilliformes: Ophichthidae) from the Marquesas Islands. AB - A new finless ophichthid eel, Apterichtus succinus sp. nov., is described based on a single specimen collected from the Marquesas Islands. The new species closely resembles A. klazingai Weber, 1913 in the shape and coloration of its head and its total vertebral count. The former differs from the latter in having more preopercular pores (4 vs. 3), fewer preanal vertebrae (54 vs. 56-63), a single tooth on the prevomer (generally absent), a shorter head (14.8 in TL vs. 12-14 in TL), and larger spots on its head and nape. Three species of Apterichtus (A. succinus, A. klazingai, and Apterichtus mysi McCosker & Hibino, 2015) are recognized from the Marquesas Islands. PMID- 27395166 TI - Review of subgenus Daphaenisca Kiriakoff, 1953 (Lepidoptera: Erebidae:
Arctiinae: Synthomini: Thyretina), with identification keys, and description of three new species. AB - We reviewed the subgenus Daphaenisca Kiriakoff, 1953 created for the single species Pseudapiconoma daphaena Hampson, 1898, in order to separate it from the other species included in the genus Pseudapiconoma Aurivillius, 1881. However, Kiriakoff's diagnosis was entirely based on the differences in the shape of the uncus among the subgenera Daphaenisca, Pseudapiconoma and Balacra Hampson, 1914. This study provides new, more accurate descriptions of the group, taking into account the differential characters and possible synapomorphies within the subgenus Daphaenisca. Our findings are supported by three new species recently discovered in Gabon and Ghana, belonging to the subgenus Daphaenisca: Balacra (Daphaenisca) inexpectata sp. n.; Balacra (Daphaenisca) magnoloi sp. n.; Balacra (Daphaenisca) flava sp. n. PMID- 27395167 TI - Three new species of the ant-mimetic plant bug genus Pilophorus from Japan (Hemiptera: Heteroptera: Miridae: Phylinae: Pilophorini). AB - Three new species of the ant-mimetic plant bug genus Pilophorus Hahn, P. maeharai, P. nakatanii and P. tagoi, are described from Japan, with information on their host associations. The genus is briefly diagnosed and discussed, including P. typicus (Distant) which is assumed to have two genotypes based on mitochondrial sequence data. The generic placement of P. tagoi, at first sight reminiscent of a certain member of Pherolepis Kulik, is also proven definitely. A checklist of all currently known species of Pilophorus in Japan is provided, with compiled distribution and host records. PMID- 27395168 TI - The gastrointestinal helminths of Rattus niobe (Rodentia: Muridae) with descriptions of two new genera and three new species (Nematoda) from Papua New Guinea and Papua Indonesia. AB - Cestodes, to be identified elsewhere, the acanthocephalan Moniliformis moniliformis and 15 species of nematode including 2 new genera, a new species and 2 putative new species from the families Heligmonellidae and Oxyuridae, as well as juveniles and a putative heligmonellid that could not be fully identified, were collected from the digestive tracts of 34 Rattus niobe (Muridae: Murinae: Rattini) from Papua, Indonesia and Papua New Guinea. The ascaridid, Toxocara mackerrasae, the chabertiid Cyclodontostomum purvisi, the heterakid Heterakis sp., the spirurids Protospirura kaindiensis and P. muricola the subulurid Subulura andersoni and the trichurids Eucoleus sp. and Trichuris muris have been reported previously from endemic Rattus spp. Syphacia (Syphacia) niobe n. sp. was distinguished from its congeners by a combination of characters including a round cephalic plate, the lack of cervical and lateral alae, a longer male tail and an attenuated female tail. Nugininema titokis n. gen., n. sp. differs from all other genera in the Heligmonellidae in the characters of the synlophe, 10-17 ridges orientated subfrontally at mid body and 2 right ventral ridges hypertrophied anteriorly. Rodentanema aenigma n. gen., n. sp. differs from all other genera in the Heligmonellidae in the characters of the synlophe 6-7 ridges at mid body not symmetrical in relation to frontal axis. Species richness of the nematode assemblage was similar to that reported for Rattus leucopus in Papua New Guinea, with about 90% of possible species found as indicated by bootstrap analysis. Species composition included 6 species unique to R. niobe and 7 species reported from at least one other species of Rattus indigenous to New Guinea, as well as juvenile worms, probably ascaridids. PMID- 27395169 TI - Ooencyrtus (Hymenoptera: Encyrtidae), egg parasitoids of the pistachio green stink bugs (Hemiptera: Pentatomidae) in Iran. AB - This paper deals with three species of Ooencyrtus Ashmead (Hymenoptera: Encyrtidae) obtained from eggs of the green stink bug, Brachynema germarii (Kolenati) (Hemiptera: Pentatomidae) infesting pistachio plants in Iran. Two new species, Ooencyrtus iranicus Hayat & Mehrnejad, sp. nov. and O. pistaciae Hayat & Mehrnejad, sp. nov., are described, and O. telenomicida (Vassiliev) is newly recorded from Iran, redescribed and illustrated. A key to some species considered similar to the species treated here is also given. PMID- 27395170 TI - Description of the female terminalia of twelve species of Proconiini and a key to genera from Argentina (Insecta: Hemiptera: Cicadellidae). AB - The female terminalia of 12 sharpshooter species are described and illustrated: Aulacizes basalis, A. conspersa, A. insistans, A. obsoleta, A. quadripunctata, Cicciana latreillei, Pseudometopia amblardii, Stictoscarta sulcicollis, Tretogonia bergi, T. cribata, T. dentalis, and T. notatifrons. A key to the identification of the Argentinean Proconiini genera including male and female characters is provided. PMID- 27395171 TI - A new species of Trichomycterus (Siluriformes: Trichomycteridae) from the upper rio Magdalena basin, Colombia. AB - Trichomycterus tetuanensis, new species, is described from the rio Tetuan, upper rio Magdalena basin in Colombia. The new species is distinguished by its margin of caudal fin conspicuously emarginate, in combination with a high number of opercular odontodes (21-39), reflected externally in the large size of the opercular patch of odontodes, 3 irregular rows of conic teeth in the upper jaw, 42-52 interopercular odontodes, 8 branchiostegal rays, 37 post Weberian vertebrae, 7 branched pectoral-fin rays, hypural 3 separated from hypural plate 4+5, and background coloration light brown with darker dots uniformly sparse on dorsum and sides of trunk. Some apomorphic characters informative for the phylogenetic affinities of the new species within Trichomycterus are discussed. PMID- 27395172 TI - Systematics and phylogeny of the genus Caenomastax Hebard, 1923
(Orthoptera: Eumastacidae: Eumastacinae). AB - Eumastacinae are well-recognized because most genera feature showy colors, and because of particular morphological characteristics of the phallic complex. This orthopteran subfamily includes the genus Caenomastax, distributed in mid elevations in the departments of Boyaca, Cundinamarca and Santander in Colombia. Three new species are described for this genus: Caenomastax similis n. sp., C. bimaculata n. sp. and C. magdalenensis n. sp. A phylogenetic analysis was performed based on morphological characters for 10 species (five ingroup and five outgroup) and 61 characters, which comprised external and genital morphology. Among the main results cast by this analysis was the proposition of Hebardomastax n. gen., within which C. atopa was previously placed, and a clarification was made on the status of the genus Zeromastax. Using the analyzed characters, an identification key is proposed for the genus. PMID- 27395173 TI - A new genus in the family Flatidae with one new combination and three new species (Hemiptera: Fulgoromorpha). AB - Herbiflata gen. nov., the second genus in the tribe Nephesini from China, is erected with Hilavrita xizangensis Chou et Lu, 1981 as its type species Herbiflata xizangensis (Chou et Lu, 1981) comb. nov. This new genus resembles Hilavrita Distant, 1906 but can be differentiated by the following characters: vertex obtusely pointed; tegmen not spotted, with orange margin; apical angle of tegmen broadly rounded; Vein ScP+R arising from one stem. Three new species, H. chromata sp. nov., H. sacra sp. nov. and H. saxeta sp. nov., are described and illustrated. A key to four species in this genus is provided. PMID- 27395174 TI - Phanoceroides Hinton, 1939: description of new species, morphology of larvae, and revised taxonomic position of the genus (Coleoptera: Elmidae)
based on molecular evidence. AB - The monotypic genus Phanoceroides was initially classified within the subfamily Elminae, based solely on the distribution and type of pubescence on the body surface. Although a close relationship with Larainae was suggested (Hinton 1939, Maier 2013), its taxonomic position and phylogeny remained unresolved. Based on newly collected material, we describe here P. fernandesi sp. n. and document morphological characters and differences of adults and larvae of P. aquaticus Hinton, 1939 and P. fernandesi sp. n. To clarify the taxonomic position of Phanoceroides within Elmidae, we used molecular data (cox1 and mtDNA). The results support position of the genus within the subfamily Larainae with Hypsilara Maier & Spangler, 2011 as a close relative. PMID- 27395175 TI - New morphological information on Simulium wygodzinskyorum Coscaron & Py-Daniel, 1989 (Diptera: Simuliidae). AB - Simulium wygodzinskyorum Coscaron & Py-Daniel was originally described based on a small number of specimens collected in Junin Province, Peru. We sampled in the same province as the type locality of this species, collecting last-instar larvae and pupae. Since the original larval description of this species was based on a single immature individual, our objective is to provide a last-instar larval description and also to provide additional morphological information on the pupa and male genitalia of this species. Some morphological characteristics not reported before for this species, such as, dorsal tubercles on larval abdominal segments, are described. Abdominal chaetotaxy of pupae is revised and the male ventral plate is fully illustrated, also it is discussed the importance of standardizing the position in which the ventral plate is illustrated. This species was collected in a stream with 2-8 m in width, exposed to sunlight with rocks of different sizes, in low density. PMID- 27395176 TI - Natural history of the mistletoe-feeding Thereus lomalarga (Lepidoptera, Lycaenidae, Eumaeini) in Colombia. AB - The natural history and morphology of the immature stages of the butterfly Thereus lomalarga Robbins, Heredia & Busby are described and illustrated. The food plant is Oryctanthus alveolatus (H.B.K.) Kuijt (Loranthaceae). Chaetotaxy of the first instar is described and compared with that of three locally studied Thereus species. Larvae have four instars, and the dorsal nectary organ becomes functional in the third instar. They are facultatively tended by ants belonging to seven genera that are attracted to O. alveolatus by floral disc nectaries, honeydew producing Hemiptera, and secretory wounds produced by Hemiptera on the fleshy inflorescence rachis. The average period from egg to eclosion under lab conditions was 35.68 days. Females emerged before males. Adults of both sexes feed on nectar from the flowers of the food plant and on hemipteran secretions; adults were not observed feeding on other flowers. Campopleginae and Chalcidinae were the most important parasitoids. PMID- 27395177 TI - A new species of the genus Terebellides (Polychaeta, Trichobranchidae) from the Iranian coast. AB - Based on specimens collected during several sampling programmes along the Iranian coast, Persian Gulf, a new species of the genus Terebellides (Polychaeta, Trichobranchidae) is herein described as Terebellides persiae spec. nov. The new species is primarily characterised by the presence of a large dorsal thoracic hump in larger specimens and ciliated papillae on the branchial lamellae. The new species is compared with other taxa belonging to Terebellides described or reported with any of both characters. SEM and micro-CT have been used to study T. persiae spec. nov. and provide several new details on external characters and internal organs, respectively. A key for the identification of the species of Terebellides with dorsal hump is provided. PMID- 27395178 TI - A new species of gecko (Squamata: Diplodactylidae: Strophurus) from north Queensland, Australia. AB - A new species of diplodactylid gecko in the genus Strophurus Fitzinger, from north Queensland, Australia, is described herein as Strophurus congoo sp. nov. It is a small, pale grey to tan, unpatterned or faintly striped gecko, resembling the phasmid geckos in appearance, habitat and behaviour. However, within Strophurus it is not closely related to the phasmid geckos. It is distinguished from all other Strophurus by a combination of even scalation, dull colouration, small size and short tail length. It is only known to occur in a restricted area of the northern Great Dividing Range, within the Einasleigh Uplands bioregion, in a relatively infertile area of rolling, largely granitic hills, and is only known from spinifex (Triodia) hummock grasslands in open woodland. PMID- 27395179 TI - Notes on the Metrocoris lituratus group (Heteroptera: Gerridae: Metrocoris) with descriptions of four new species in Sichuan Basin from China. AB - This paper provides the descriptions of four new species from eastern and southern regions of the Sichuan Basin in China: Metrocoris astictus sp. nov. and M. falciformis sp. nov. from Sichuan Province, M. guizhouensis sp. nov. and M. zhengi sp. nov. from Guizhou Province. M. sichuanensis Chen & Nieser, 1993 is currently transferred from the M. stali group to the M. lituratus group. A junior synonym M. bui Chen & Zettel, 1999 is proposed. Photographs of the male and female dorsal habitus and male genitalic structures are provided, accompanied by line drawings of male forelegs, endosomal structures and a distributional map of the newly described species. Finally, a key to the males of the species assigned to M. lituratus group is also provided to assist in identification. PMID- 27395181 TI - An appraisal of Typilobus Stoliczka, 1871 (Crustacea, Brachyura, Leucosioidea), with description of a new family and genus. AB - Since its description, Typilobus Stoliczka, 1871, has become something like a catch-all taxon to accommodate fossil leucosioid crabs with uncertain affinities. As many as 17 species have been assigned to Typilobus, recorded from the Eocene to Miocene strata of Europe, Africa, and Asia. The re-examination of the type species, Typilobus granulosus Stoliczka, 1871, from the Miocene of Pakistan, has shown inconsistency in its description and published figures leading to the need of a revision of all species assigned to Typilobus. Typilobus boscoi Via Boada, 1959, from the Middle Eocene of Spain, is revised and assigned to Folguerolesia n. gen. Characters present on ventral portions of male and female specimens differ from all known representatives of Leucosioidea, although the general morphology supports inclusion in this superfamily. A new family, Folguerolesiidae n. fam. is thus erected to accommodate Folguerolesia boscoi comb. nov., leading to recognition of three families of leucosioid crabs, including Iphiculidae and Leucosiidae. PMID- 27395180 TI - New species Victoriopisa bruneiensis and Apocorophium acutum (Chevreux, 1908) from Brunei (Crustacea: Peracarida: Amphipoda). AB - One new and one invasive species of amphipod are described from the subtidal waters of Brunei. The new species Victoriopisa bruneiensis (Melitidae) and the invasive species Apocorophium acutum (Chevereux, 1908) (Corophiidae) were collected from the Sungai Brunei Estuary. Victoriopisa bruneiensis sp. nov. is one of only four Victoriopisa where the eyes are present. An updated key to twelve world species of Victoriopisa is provided. Apocorophium acutum occurs in high density algal matts on pylons/rocks. This is the sixth species of Apocorophium described for the genus. PMID- 27395182 TI - A new species of genus Ephemeroporus Frey, 1982 (Cladocera: Anomopoda: Chydoridae) from Peninsular Malaysia. AB - Study of Ephemeroporus Frey, 1982 populations from Peninsular Malaysia revealed a new species. Ephemeroporus malaysiaensis sp. nov. is characterized by the presence of four-five large denticles on anal margin of postabdomen instead of two-three, and five distinctive pigmented spots on each valve. Pigmented spots on the valves were never recorded for any species of family Chydoridae. E. malaysiaensis sp. nov. seems to be another endemic Chydoridae species of South East Asia. E. malaysiaensis sp. nov. is a rare species, associated with emergent macrophytes in the littoral zone of shallow lake. Most of Ephemeroporus populations from Peninsular Malaysia belong to eurybiotic Paleotropical species Ephemeroporus barroisi (Richard, 1984). PMID- 27395183 TI - A review of the genus Dryinus Latreille, 1804 (Hymenoptera, Chrysidoidea, Dryinidae) from Iran, with description of a new species. AB - Three species of the genus Dryinus Latreille, 1804 from Iran are reviewed and keyed. Dryinus tamaricicola sp. nov. is described and illustrated. Dryinus tarraconensis Marshall, 1868 is newly recorded from Iran. Key to the Palaearctic species of Dryinus group 3 are modified. PMID- 27395184 TI - Two new species and a key to nine species of the genus Mongolotettix Rehn, 1928 from China (Acrididae, Acridoidea, Orthoptera). AB - Two new species of the genus Mongolotettix Rehn, 1928 from China, i.e. Mongolotettix wulingyuanensis sp. nov. and Mongolotettix. shaanxiensis sp. nov. are described herein. M. wulingyuanensis sp. nov. is similar to M. angustiseptus Wan, Ren & Zhang, 1998, but differs from the latter by body larger, length of body ? 25.6 mm, ? 39.1mm; tegmina of male without a white stripe on the fore margin at base; subgenital plate of male conical, sides concave, apex acute; both outer sides of epiphallus without acute projection in the middle. M. shaanxiensis sp. nov. is similar to M. anomopterus (Caudell, 1921), but differs from the latter by tegmina of male longer, reaching the end of epiproct, without a white stripe on the fore margin at base, tegmina of female longer, reaching the middle of 2nd abdominal tergum, width of epiphallus larger than height, upper ovipositor valve slender, length 3.8 times its maximum width. A key to all nine known species of the genus from China is given. Type specimens are deposited in the Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, 810001, China. PMID- 27395185 TI - Three new species of Pararhabdepyris Gorbatovsky (Hymenoptera, Bethylidae) from Central Africa and the Arabian Peninsula. AB - Three new species of Pararhabdepyris are described and illustrated: P. arabo sp. nov. (United Arabian Emirates and Yemen), P. wafrika sp. nov. (Central African Republic), P. ngangu sp. nov. (Central African Republic). The genus is recorded for the first time from the Saharo-Arabian region. A key for all species of the genus is presented. PMID- 27395186 TI - A new species in the genus Crisicoccus Ferris (Hemiptera: Coccomorpha: Pseudococcidae), with a key to Chinese species. AB - A new mealybug, Crisicoccus ziziphus sp. nov. (Hemiptera: Coccomorpha: Pseudococcidae), collected on the leaves and twigs of Ziziphus jujuba (Rhamnaceae), is described from China. All the female developmental stages (adult, third-instar, second-instar and first-instar nymphs) are described and illustrated. Keys are provided to separate the female instars and to identify adult females of Crisicoccus species from China. PMID- 27395187 TI - A new species of guitarfish, Rhinobatos borneensis sp. nov. with a redefinition of the family-level classification in the order Rhinopristiformes (Chondrichthyes: Batoidea). AB - A new guitarfish, Rhinobatos borneensis sp. nov., is described from material collected at fish markets in Malaysian Borneo (South China Sea). This ray, which is almost plain coloured with faint orange blotches in adults, has a more colourful embryo marked with small pale ocelli with dark centres. Confused with R. schlegelii (Japan to Taiwan) and its junior synonym R. formosensis, new molecular data suggests it is more closely related to a subgroup of Rhinobatos from the Indo-Malay Archipelago that includes R. jimbaranensis, R. sainsburyi and R. whitei. Based on evidence from recent phylogenetic studies, the genus Rhinobatos is non-monophyletic, nor is the Rhinobatidae a monophyletic family level group. Former subgenera of Rhinobatos, Acroteriobatus and Glaucostegus, are valid genus-level taxa supported by both morphological and molecular evidence. Moreover, amphi-American members of Rhinobatos, assigned herein to a new genus Pseudobatos, are not monophyletic with Rhinobatos, Acroteriobatus and Glaucostegus and its position within the newly erected order Rhinopristiformes needs to be reassessed. Several molecular studies have suggested that the family Rhinobatidae is polyphyletic and needs to be redefined. We propose a revised classification of the order Rhinopristiformes based on molecular analyses and supported by morphological data, making strong use of oronasal morphology. The group now contains 5 family-level taxa: three valid nominal taxa, Pristidae (2 genera, 5 species), Rhinidae (incorporating Rhynchobatidae, 2 genera, 9 species), Rhinobatidae (3 genera, 31 species); and two new taxa, Glaucostegidae (single genus, 6 species) and Trygonorrhinidae (3 genera, 8 species). PMID- 27395188 TI - Description of two new Bathyaethiops species (Teleostei: Alestidae) from the Congo basin. AB - Two new species of Bathyaethiops (Teleostei: Characiformes: Alestidae) are described. Bathyaethiops baka n. sp. is a dwarf species with the largest known specimen being only 24.4 mm SL. The species is characterized by an incomplete squamation and a large humeral spot. Bathyaethiops baka n. sp. is known so far only from the Ngoko River of Southeastern Cameroon, a tributary of the Sangha River in the northern Congo basin. The second species, Bathyaethiops flammeus n. sp., shows a diagnostic spot in front of the dorsal-fin base, which is devoid of melanophores and bright red in life. The species is described from the Bakere River at Yambula-Bakere, a locality north-west of Kisangani in the Central Congo basin. Other records of Bathyaethiops flammeus n. sp. from the Tshuapa respectively Ruki River at Boende and Eala, Central Congo basin, suggests a wider geographic distribution. A key to all species of Bathyaethiops is provided. PMID- 27395189 TI - Podocotyle nimoyi n. sp. (Digenea: Opecoelidae: Plagioporinae) and a re description of Podocotyle pearsei Manter, 1934 from five species of deep-sea macrourids from the Gulf of Mexico and Caribbean Sea. AB - Two rare species of Podocotyle Dujardin, 1845 (Digenea: Opecoelidae) parasitizing five macrourid species inhabiting the deep waters of the northeastern Gulf of Mexico and Caribbean Sea off Panama are described. Podocotyle nimoyi n. sp. was found in the intestine of the pugnose grenadier, Sphagemacrurus grenadae (Parr), and the common Atlantic grenadier, Nezumia aequalis (Gunther) (Gadiformes: Macrouridae), at depths of 534-995 m in the Northeast Gulf of Mexico off Florida and represents the fifth species of Podocotyle endemic to the deep sea. Podocotyle pearsei Manter, 1934, was re-described from the intestine of the bullseye grenadier, Bathygadus macrops Goode & Bean, the doublethread grenadier, Gadomus arcuatus (Goode & Bean), and the western softhead grenadier, Malacocephalus occidentalis Goode & Bean (Gadiformes: Macrouridae), collected from 591-728 m depths in the Northeast Gulf of Mexico off Florida and the Caribbean Sea off Panama. The following new host records are established: P. nimoyi n. sp. is the third parasite species known from S. grenadae and the first digenean species reported from this host; P. nimoyi n. sp. is the first reported species of Podocotyle parasitizing N. aequalis; and this is the first report of P. pearsei or any representative of the genus Podocotyle infecting B. macrops, G. arcuatus and M. occidentalis. A listing of all digenean parasites previously reported from the five macrourid species examined herein is given and some observations are made about Podocotyle in the deep sea. PMID- 27395190 TI - Pachyneuridae (Diptera): new data on the geographic range and designation of the lectotype of Pachyneura fasciata Zetterstedt, 1838. AB - All available records of two nematoceran flies Pachyneura fasciata and P. oculata were gathered and mapped. P. fasciata is a wide-ranging Palaearctic species, and is here reported for the first time for some regions of the Russian Federation, including the European part of Russia (Leningrad Oblast), Western Siberia (Tomsk Oblast, Altay Republic), Eastern Siberia (Krasnoyarsk Krai, Irkutsk Oblast, Chita Oblast), the Far East of Russia (Kuril islands, Kunashir and Paramushir Islands), and for continental China. Pachyneura oculata has a restricted eastern Palaearctic range. The lectotype of P. fasciata has been designated and a key for the identification of Pachyneura species is provided. PMID- 27395191 TI - Rediscovery and a new record of Hemidactylus laevis (Reptilia: Gekkonidae) from Somaliland, with notes on and resurrection of Hemidactylus fragilis. AB - Hemidactylus laevis, a gekkonid lizard originally described from the Gaan Libah Mountains in Somaliland, is recorded herein from Erigavo, Sanaag Region, in the same state, which represents the second-ever known specimen and locality for this species in more than 100 years since its description. The species is endemic to Somaliland. Data on morphology and natural history, as well as the first life photographs are provided. Based on morphological data we conclude the species to be closely related to H. laticaudatus. Additionally, H. fragilis from southern Somalia and extreme south-east Ethiopia is resurrected from the synonymy of H. frenatus based on morphological data. PMID- 27395192 TI - A new species of Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae) from Guizhou, China. AB - A new species of the genus Hemiphyllodactylus is described from Huishui County, Guizhou Province, Southwest China. Hemiphyllodactylus huishuiensis sp. nov. is distinguished from all other congeners by having the unique combination of the following characters: a maximum SVL of 51.2 mm; 8 or 10 chin scales; enlarged postmental scales; 3 circumnasal scales; 2 or 3 scales between the supranasals; 9 11 supralabials; 9-11 infralabials; 13-15 dorsal scales; 7-9 ventral scales; a lamellar hand formula of 3-4-4-4 or 4-4/5-5-4; a lamellar foot formula of 4-4/5-5 4/5; 3 subdigital lamellae on the first finger and first toe; a continuous precloacal and femoral pore series of less than 20; one cloacal spur in both males and females; no enlarged subcaudal scales; dark dorsal transverse blotches; dark postorbital stripe; a brown postsacral mark bearing anteriorly projecting arms; and unpigmented caecum and gonads. The new species also occurs in Ziyun County, Guizhou Province, China. PMID- 27395193 TI - New species of Elampus Spinola, 1806 (Hymenoptera: Chrysididae), with a key to the Neotropical species of the genus. AB - Three species of Elampus Spinola are reviewed. A new species, Elampus macuxi Lucena, sp. nov. (Brazil, Roraima) is described and illustrated. The lectotype is designated for Elampus aequinoctialis Ducke 1901. A key for three Neotropical species is given. PMID- 27395195 TI - Revision of the Scytinopteridae (Hemiptera: Cicadomorpha: Scytinopteroidea) of the Queensland Triassic. AB - The extinct hemipteran family Scytinopteridae, the presumed ancestors of the Heteroptera, was a small but widely distributed element of the Triassic insect fauna of Queensland. A total of 28 tegmina have been collected at six sites (Gayndah, Esk, Mount Crosby, Riverview, Denmark Hill and Dinmore) in five Middle or Late Triassic Formations. The specimens are remarkably uniform in both wing shape and basic venation, and the generally weakly developed venation of the apical area of the tegmen is rarely clearly preserved. Some consistent variations in tegmen size and in minor venational characters, however, have enabled the identification of six and possibly seven species in three genera, acknowledging of course, the somewhat artificial nature of fossil insect species based solely on isolated wings. Mesoscytina Tillyard, 1919 (= Triassoscarta Tillyard, 1919, syn. nov.), comprising Mesoscytina australis Tillyard, 1919 (= Mesoscytina affinis Tillyard, 1919, syn. nov., = Triassoscarta subcostalis Tillyard, 1919, syn. nov.) (Denmark Hill, Esk), Mesoscytina fistulae sp. nov. (Mount Crosby, Gayndah), Mesoscytina woodsi sp. nov. (Gayndah), and Mesoscytina magna sp. nov. (Dinmore), is distinguished by the combination of the R more or less straight distally and M with three apical branches. The monotypic Eurymelidium Tillyard, 1919, with type species Eurymelidium australe Tillyard, 1919 (Denmark Hill, Dinmore), has R sinuous and M with two apical branches, and the monotypic Apheloscyta Tillyard, 1922, with type species Apheloscyta mesocampta Tillyard, 1922 (Denmark Hill, Riverview) has R more or less straight and M with two apical branches. Three poorly preserved and thus unidentifiable scytinopterid tegmina from Esk, similar in size to Mesoscytina fistulae, are designated as Esk species A. PMID- 27395194 TI - Odontalgus dongbaiensis sp. n. from eastern China, and a world catalog of
Odontalgini (Coleoptera: Staphylinidae: Pselaphinae). AB - Odontalgus dongbaiensis Yin and Zhao, new species is described from the eastern Chinese province of Zhejiang. This represents the first record of the tribe Odontalgini Jeannel, 1949 in China. The habitus, foveal pattern, and major diagnostic characters of the new species are illustrated, and the new species is diagnosed and compared with related congeners. A catalog of the world genera and species of Odontalgini is provided, with a full bibliography of the original descriptions and synonyms. Data on the type locality, type depository, and world distribution of each species are given. Odontalgus gracilides Newton, new replacement name, is proposed for O. gracilis Jeannel, 1964, which is a primary junior homonym of O. gracilis Raffray, 1904. Odontalgus vespertinus rhodesiae Jeannel, 1951 is synonymized with O. vespertinus Raffray, 1877, new synonym. Odontalgus rugulosus Jeannel, 1957 is selected as the correct original spelling of this species. Currently the Odontalgini contains fifty-six species and three subspecies grouped in five genera, with a disjunct distribution in the Afrotropical and Oriental regions, Korea, Japan, and Australia. PMID- 27395196 TI - A taxonomic study of the genus Eupteryx Curtis (Hemiptera: Cicadellidae: Typhlocybinae), with description of five new records and one new species from China. AB - A new species, Eupteryx (Stacla) gracilirama sp. nov. from China is described and illustrated and five species are recorded for the first time from China: Eupteryx (Stacla) janeki Dworakowska, Eupteryx (Stacla) albonigra Dworakowska, Eupteryx (Stacla) hela Dworakowska, Eupteryx (Stacla) irminae Dworakowska and Eupteryx (sensu stricto) stachydearum (Hardy). A check-list and key to all known species of Eupteryx from China are provided. PMID- 27395197 TI - Erratum: ARTHUR ANKER & PAULO P.G. PACHELLE (2016) Mud-shrimps of the genus Axianassa Schmitt, 1924 from Panama, with description of two new species (Decapoda: Gebiidea: Laomediidae). Zootaxa, 4111(2): 101-125. PMID- 27395198 TI - Heteropsis (Nymphalidae: Satyrinae: Satyrini: Mycalesina): 19 new species from Madagascar and interim revision. AB - The genus Heteropsis Westwood, 1850 is monophyletic and contains the most diverse evolutionary radiation of butterflies in the Malagasy Region, with 46 up to now known species (53 accepted taxa) and at least 23 undescribed species in collections to date. Mixed species in historical descriptions and lost types in this genus have hindered taxonomic progress until now. A lectotype female is thus designated for the only surviving syntype that can be found for Mycalesis andravahana Mabille, 1878. Mycalesis difficilis Mabille, 1880 and three names of Oberthur, 1916 lectotypified here, Henotesia undulosa, Henotesia undulosa var. luctuosa and Henotesia andravahana var. macrophthalma, newly become its synonyms. A lectotype is also specified for Gallienia alaokola Oberthur, 1916. These acts now clarify potential confusion among the minimum of five species that these two nominal taxa represent, and thus facilitate description of related species compromised by the original descriptions (for one of which, the name Henotesia andravahana ab. marmorata Aurivillius, 1925 is unavailable). To solidify description of similar species, lectotypes are also designated for the following nominal species of Oberthur, 1916: Culapa comorana, C. pauper, Culapa ("var. ou espece separee") pseudonarcissus, C. laeta, C. laetifica, C. anceps, C. undulata, C. turbans, C. curvatula, C. ornata, C. pallida, and of Oberthur, 1923: C. houlbertiana, and also for Mycalesis iboina Ward, 1870, M. strigula Mabille, 1877, M. maeva Mabille, 1878, M. ankoma Mabille, 1878, M. irrorata Mabille, 1880 and M. butleri Mabille, 1880. The following 19 new species are described within Heteropsis from Madagascar, which are organised within species groups that are briefly characterised and discussed: in the Ht. exocellata group, Heteropsis mimetica Lees & Kremen, sp. nov.; in the Ht. antahala group, Heteropsis hazovola Lees & Raharitsimba, sp. nov.; in the Ht. drepana group, Heteropsis harveyi Lees & Kremen, sp. nov.; Heteropsis vanewrighti Lees, sp. nov.; Heteropsis westwoodi Lees, sp. nov., Heteropsis pauliani Lees, sp. nov.; Heteropsis imerina Lees, sp. nov.; in the Ht. subsimilis group, Heteropsis kremenae Lees, sp. nov.; Heteropsis avaratra Lees & Kremen, sp. nov. Heteropsis sogai Lees, sp. nov., and in the Ht. strigula group, Heteropsis tornado Lees, Allaoui & Aduse-Poku, sp. nov., Heteropsis lanyvary Lees, sp. nov.; Heteropsis barbarae Lees & Kremen, sp. nov.; Heteropsis menamenoides Lees, sp. nov.; Heteropsis roussettae Lees & Kremen, sp. nov.; Heteropsis tianae Lees & Kremen, sp. nov.; Heteropsis oberthueri Lees, sp. nov.; Heteropsis borgo Lees, sp. nov. and Heteropsis vertigo Lees & Raharitsimba, sp. nov. Counting the resulting synonymy of Heteropsis difficilis (Mabille, 1880), with Ht. andravahana (Mabille, 1878), this brings the Malagasy Heteropsis fauna to 64 species, about 2/3 of which are here revised. PMID- 27395199 TI - Review of the fish-parasitic genus Cymothoa Fabricius, 1793 (Crustacea: Isopoda: Cymothoidae) from Australia. AB - The genus Cymothoa Fabricius, 1793 is revised for Australian waters. Cymothoa hermani Hadfield, Bruce & Smit, 2011, previously known from Tanzania on the host Selar crumenophthalmus (Bloch, 1793) is new to Australian waters. Cymothoa carangi Avdeev, 1979; Cymothoa epimerica Avdeev, 1979; Cymothoa parupenei Avdeev, 1979; Cymothoa propria Avdeev, 1979; Cymothoa rotunda Avdeev, 1979 and Cymothoa pulchrum Lanchester, 1902 are redescribed. Cymothoa curta Schioedte & Meinert, 1884, first described from the host Anableps anableps (Linnaeus, 1758); and Cymothoa plebeia Schioedte & Meinert, 1884, first described from Cape Verde; are redescribed and excluded from the Australian fauna. Cymothoa limbata Schioedte & Meinert, 1884 is placed into junior synonymy with Cymothoa eremita (Brunnich, 1783). A key to the Australian species of Cymothoa is presented. PMID- 27395200 TI - A new genus of anthophilous drosophilids, Impatiophila (Diptera, Drosophilidae): morphology, DNA barcoding and molecular phylogeny, with descriptions of thirty nine new species. AB - Breeding habits of essential dependence on flowers for larval food resources have evolved repeatedly in separate lineages of the Drosophilidae. However, flowers of Impatiens L. have never been recognized as hosts for drosophilid flies until recently: two Hirtodrosophila species, H. actinia (Okada) and H. yapingi Gao, were found feeding and breeding on Impatiens flowers. During our recent field surveys in central and southern China, a great number of drosophilid flies morphologically resembling the two species were collected, almost exclusively from flowers of Impatiens (family Balsaminaceae) and the family Gesneriaceae. In the present study, these specimens were identified on the basis of morphological characters and/or partial DNA sequences of the mitochondrial COI (cytochrome c oxidase subunit I gene, used as a barcoding marker). As a result, 39 new species were recognized. We then reconstructed the phylogenetic relationships among most of them, based on concatenated DNA sequences (3047 nucleotide sites) of two mitochondrial (COI and COII, i.e., cytochrome c oxidase subunits I and II, respectively) and three nuclear genes (ATPsyn-alpha, alphaTub84B and Hsc70cb, i.e., ATP synthase alpha, alpha-Tubulin at 84B and Hsc70Cb isoform H, respectively). In the resulting Bayesian and ML (maximum likelihood) trees, three well-supported clades were recognized, with a few species having remained uncertain for their phylogenetic positions. We also conducted a cladistic analysis with data of adult morphological characters to investigate the phylogenetic positions of a few species of which DNA sequence data were not available, and to investigate the classification of species groups with definition of their diagnoses. In consequence, we established a new genus, Impatiophila, for the species visiting flowers of Impatiens and Gesneriaceae, described all the new species, and revised the taxonomy of some known species. PMID- 27395201 TI - New taxa and arrangements within the family Latrunculiidae (Demospongiae, Poecilosclerida). AB - Extensive new collections of latrunculid sponges from British Columbia, the Aleutian Islands, and the Gulf of Alaska, have extended the distributions of known species Latrunculia oparinae Samaai & Krasokhin, 2002, from the Russian Sea of Okhotsk, L. velera Lehnert et al., 2006, from the Aleutian Islands, and L. austini Samaai et al., 2006, from British Columbia. New material has facilitated detailed re-descriptions of these species and in situ images have improved our understanding of their living morphology and ecology. Several new species of Latrunculia were discovered within these collections: sympatric species Latrunculia hamanni sp. nov. and L. oparinae are described here and differentiated from each other by various field characteristics, and L. lincfreesei sp. nov. is described from the Gulf of Alaska. In terms of their higher systematics, L. austini and L. hamanni sp. nov. are recognisable within the subgenus Latrunculia du Bocage, 1869, and L. lincfreesei sp. nov. in subgenus Biannulata Samaai et al., 2006. A third subgenus, Uniannulata subgen. nov., is proposed for L. oparinae, L. velera and several fossil species in southern New Zealand and Western Australian Eocene fossiliferous sediments. In all of these species the subsidiary whorl, apical whorl, and apex of the anisodiscorhabd are fused. Living species of Uniannulata subgen. nov. are thus far restricted to the North Pacific Ocean. A new genus, Bomba gen. nov., is proposed for a rare latrunculid species, Bomba endeavourensis gen. et sp. nov., discovered in deep waters on British Columbia's Endeavour Ridge. Finally, Latrunclava gen. nov. is proposed for species with long, sceptre-like anisoconicorhabds in addition to the typical, smaller anisodiscorhabds; Latrunclava imago gen. et sp. nov. is described from the central Aleutian Islands. PMID- 27395202 TI - A new subspecies of Ovalona setulosa (Megard, 1967) (Cladocera: Anomopoda: Chydoridae) from the Caribbean coast of Colombia. AB - A new subspecies of Ovalona setulosa (Megard, 1967) (Cladocera: Anomopoda: Chydoridae) is described based on material from Laguna Navio Quebrado (La Guajira Department), Colombia. Ovalona setulosa arangureni ssp. nov. differs from the nominative subspecies in: (1) major head pores position on head shield; (2) posterior margin of labral keel without clusters of short setules; (3) more elongated postabdomen, with length/height ratio about 2.7-3; (4) male postabdomen with straight dorsal margin in whole distal portion. In outer morphology and morphology of postabdomen, O. setulosa arangureni ssp. nov. can be confused with O. glabra (Sars, 1901), but, like nominative subspecies, differs from it by interrupted connection between major head pores. Our data suggest that diversity of Aloninae species with limited distribution areas in South America is underestimated yet, and areas north and south of Amazon basin can have different local species. PMID- 27395203 TI - The Simulium nigritarse subgroup (Diptera: Simuliidae) in Uganda: New species and country records. AB - Amongst blackfly samples from western Uganda three different morphospecies of the Simulium (Nevermannia) nigritarse Coquillett subgroup were identified. Of these, S. perforatum Fain & Dujardin showed the widest distribution and is reported from Uganda for the first time. In addition, two new species are described: S. bwambanum sp. nov. and S. itwariense sp. nov. Diagnostic characters are the different structures of the pupal cocoon, the configurations of the gill filaments and adult colour features. PMID- 27395204 TI - A new species of the genus Glischrochilus Reitter (Coleoptera: Nitidulidae: Cryptarchinae) from China. AB - The cosmopolitan genus Glischrochilus Reitter, 1873 (Nitidulidae: Cryptarchinae) is distributed in Holarctic and Oriental regions. According to the most recent catalogue (Jelinek & Audisio 2007), 32 species are known from the Palaearctic region. In China the genus is represented by 13 species, most of which were described by Jelinek (1975, 1982, 1999) and Lason (2009). PMID- 27395205 TI - Kryptosega Kimsey, 1986 (Hymenoptera, Chrysididae) is newly recorded genus from Oriental Region, with description of one new species. AB - The genus Kryptosega Kimsey 1986 was described in the subfamily Amiseginae with two new species, K. anomala Kimsey and K. kaindeana Kimsey from New Guinea (Kimsey 1986). Later third species K. mweramwera Villemant was described from Vanuatu (Villemant et al. 2012). The genus resembles Indothris Krombein, 1957 by having head with occipital carina, mesopleuron without scrobal sulcus, and hind coxa without dorsobasal carina, but differs from the latter by having metanotum without median enclosure, and propodeum rounded posterolaterally (Kimsey & Bohart 1991). Amiseginae are the parasites of the eggs of walking stick insects (Phasmida) and can be found in the low vegetation or leaf litter (Kimsey & Bohart 1991). However, the biology of Kryptosega is still unknown (Villemant et al. 2012). PMID- 27395206 TI - Description of the male of Acentrus boroveci Kostal, 2014 (Coleoptera: Curculionidae: Acentrusini). AB - The male of the recently described Acentrus boroveci Kostal, 2014 is described for the first time, and characters to differentiate it from males of the two other species of Acentrus Desmarest, 1839 are given. PMID- 27395207 TI - A redescription of Protolimnesia longa Besch, 1963 from Bolivia, with the first description of the female (Acari: Hydrachnidia: Limnesiidae). AB - The water mite genus Protolimnesia Lundblad, 1927 is distributed in South and Central America, the Caribbean (Haiti) and southern parts of the USA (Goldschmidt 2004). One odd record is known from Oman (Smit & Pesic 2010). In addition to the nominate subgenus, the genus also includes Protolimnesella Cook, 1980 and Voldroguella Cook, 1981, typical inhabitants of interstitial habitats (Goldschmidt 2004). The nominate subgenus includes seven species and subspecies, most of them are stream-dwellers, but Protolimnesia longa Besch, 1963 appears to be a characteristic inhabitant of the interstitial of intermittent streams. This species was described by Besch (1963) based on a single male from the interstitial of a dry stream at 1200 m altitude in Argentina. Since then, no further records of this species were published. In the original description Besch (1963) illustrated only the ventral and dorsal side. Smit (2002) and Goldschmidt (2004) re-examined the holotype of P. longa deposited in the Viets Collection (SMF) and provided illustrations of the palp and ejaculatory complex, respectively. However, some important characteristics are neither given in the original description nor are visible in the type material. Smit (2002) mentioned that both fourth legs in the holotype slide are positioned in such a way that examination of the claws of IV-L-6 is not possible, Goldschmidt (2004) stated that the ejaculatory complex in the type is mounted laterally and most probably squashed. PMID- 27395208 TI - Indonemoura annamensis-a new species of stonefly from Vietnam (Plecoptera: Nemouridae). AB - The amphinemurine genus Indonemoura Baumann (1975) was proposed for species previously included in the genera Protonemura Kempny and Nemoura Latreille. Baumann (1975) designated P. indica Kimmins, 1947 (in Kimmins 1946) as the type species. He also transferred 14 additional species from Protonemura and Nemoura into this genus. The genus is distributed mainly in the Oriental region (only one species from Tibet, close to the eastern border of the Palaearctic Region) and many new species have been added in the last decades (Zwick & Sivec 1980; Shimizu 1994a & b; Zhu et al. 2002; Li et al. 2005; Li & Yang 2005, 2006; Wang et al. 2006; Sivec & Stark 2010) including presently 53 species (DeWalt et al. 2009). Sivec & Stark (2010) first described three Indonemoura species from Vietnam, I. angulata, I. clavata, and I. tricantha. These three species are the only Indonemoura presently known for Vietnam. PMID- 27395209 TI - The mistaken manakin: a new genus-group name for Parus pipra Linnaeus, 1758 (Aves: Passeriformes: Pipridae). AB - The White-crowned Manakin Pipra pipra was long considered congeneric with other members of the genus Pipra, until Prum (1990, 1992, 1994) demonstrated that its display repertoire and syringeal morphology differ considerably from all other members of that genus. Subsequently, three different molecular phylogenies have all indicated that this manakin is more closely related to the genus Machaeropterus than to Pipra. Prum (1992) considered that the name Dixiphia Reichenbach, 1850, was available, and thus the combination Dixiphia pipra has since been in widespread use for this species. However, as first recognized more than 150 years ago, Dixiphia is a junior synonym of Arundinicola d'Orbigny, 1840. We show that no genus-group name is available for the manakin originally described as Parus pipra Linnaeus, 1758, and for which we therefore provide a new genus name. PMID- 27395210 TI - Taxonomic notes on the Lygephila vulcanea (Butler, 1881) species-group (Lepidoptera, Erebidae, Toxocampinae). AB - Present paper is dedicated to taxonomic clarification of L. vulcanea and L. lupina (=mirabilis Bryk, 1948, syn. rev.) initiated in a previous publication (Pekarsky 2014). The distribution patterns of the two species are discussed, disputing the presence of L. vulcanea in Russia. PMID- 27395211 TI - Four new species of Meligethes Stephens from China and additional data on other species of the genus (Coleoptera: Nitidulidae: Meligethinae). AB - Four new species of Meligethes Stephens, 1830, M. (s.str.) macrofemoratus (Shaanxi, Ningxia), M. (s.str.) yak (NW Sichuan), M. (s.str.) auropilosus (Tibet) and M. (Odontogethes) aurorugosus (Tibet) spp. nov., are described and illustrated from China. Diagnostic characters distinguishing these new species from closely related taxa are discussed. The previously unknown male of Meligethes (s.str.) aureolineatus Audisio, Sabatelli & Jelinek, 2015 from Sichuan and the previously unknown female of M. (Odontogethes) scrobescens Chen, Lin, Huang & Yang, 2015 from Sichuan are also described. Additional data are also presented on the geographic distribution and life history of other Chinese Meligethes species. PMID- 27395212 TI - Host plant shifts and transitions into new adaptive zones in leafhoppers:
the example of Macropsinae (Homoptera: Auchenorrhyncha: Cicadellidae)
of Russia and adjacent countries. AB - The modes of diversification of Palaearctic Macropsinae (Homoptera: Auchenorrhyncha: Cicadellidae) are reconstructed based on data on their host plants and distribution in Russia and the adjacent territories. Macropsinae (Homoptera: Auchenorrhyncha: Cicadellidae) is originally an Oriental group, which penetrated into the Palaearctic from Southeast Asia. The genus Pediopsoides and species of the genus Macropsis that feed on East Asian oaks have not dispersed beyond broadleaf forests of the Eastern Palaearctic. Apparently, Pediopsis and elm-feeding species of Macropsis initially dispersed throughout the entire broadleaf forest zone. Division of this zone into two widely separated parts in temperate areas of Europe and East Asia (nemoral disjunction), produced closely related vicariant pairs of sister species. The genus Oncopsis and species of Macropsis feeding on Salicaceae dispersed throughout the entire Palaearctic following their host plants. Both lineages penetrated into riparian forests of the foothills and midlands of Central Asia, where they produced endemic species. The Central Asian Macropsis lineage shifted from Salicaceae to trees and shrubs of unrelated families (wild roses, barberry, oleaster, and sea-buckthorn) growing in the same biotopes. Subsequent diversification on those plants produced several separate host-associated species-groups, some of which penetrated following their hosts from riparian forests into arid habitats. One such lineage apparently shifted from shrubs to wormwood species (Artemisia spp.) and thus gave rise to the genus Macropsidius. This genus underwent adaptive radiation on wormwood species in the plains of South Kazakhstan and Central Asia; advancing westward, it formed secondary centres of diversity in Transcaucasia and the Mediterranean. Finally, some lineage of Macropsidius (or its sister-group) switched from feeding on Artemisia to polyphagy, yielding the ancestral form of the genus Hephathus. In general, the evolution of the Macropsis-Macropsidius-Hephathus lineage in the Palaearctic closely followed the classical Simpsonian model: the group underwent diversification within a particular adaptive zone, then one lineage entered a new adaptive zone and secondarily diversified there, etc. Transitions into new adaptive zones by different Macropsinae lineages were probably caused by one of two factors: shift to a new plant unrelated to the original host (e.g., from Salicaceae to plants of other families) or adaptation to new microclimatic conditions (penetration from riparian forests into open arid habitats). PMID- 27395213 TI - A new species of Zwicknia Muranyi (Plecoptera, Capniidae) from the French and Swiss Jura Mountains, the French Massif Central, and the French Middle Rhone Region. AB - A new species of Zwicknia Muranyi, Z. ledoarei sp. n., from the Jura Mountains of France and Switzerland, the French Massif Central, and the French Middle Rhone Region, is described on the basis of morphology and molecular methods. Information on the distribution and the ecological preferences of this new species is also provided. PMID- 27395214 TI - A new species in the genus Alectorolophus Brunner von Wattenwyl, 1898 from Indonesia with discussion on its position compared to allied genera in subfamily Catantopinae (Orthoptera: Acrididae). AB - Alectorolophus impunctus Storozhenko et Kim, sp. nov. from Sulawesi Island, Indonesia, is described here. Keys to both sexes of all known species and subspecies of Alectorolophus are also provided in this report. The position of genus Alectorolophus in the systematics of grasshoppers is clarified. It belongs to subtribe Ecphantina (Catantopinae: Catantopini) consisting of nine genera distributed in Australia and Oriental regions. The diagnosis of Ecphantina is clarified and a key to genera is provided. An annotated list of the genera and species of Ecphantina is given. Moreover, the correct name of the subfamily Coptacridinae is Coptacrinae Brunner von Wattenwyl, 1893. PMID- 27395215 TI - The water mite genus Gretacarus K.O. Viets, 1978 from Australia (Acari: Hydrachnidia, Mideopsidae: Gretacarinae), with the description of three new species. AB - Three new species of the genus Gretacarus K.O. Viets, 1984 are described from Australia, G. gereckei n. sp., G. occidentalis n. sp. and G. yorkensis n. sp.. Moreover, many new records are given for other members of the genus. PMID- 27395216 TI - Two new species of genus Hydrosmittia Ferrington & Saether (Diptera: Chironomidae) from China. AB - The genus Hydrosmittia from China is reviewed. Two new species H. continalinea sp. n. and H. sipinata sp. n. are described and illustrated based on male imagines. Key to known male imagines of genus Hydrosmittia worldwide is provided. PMID- 27395217 TI - Contribution to the taxonomy of the genus Coeleumenes van der Vecht, 1963 (Hymenoptera: Vespidae: Eumeninae) from Vietnam, with description of a new species. AB - Coeleumenes flavus sp. nov is described and illustrated from Vietnam (Son La), C. burmanicus van der Vecht, 1963 is redescribed. A key to both species from Vietnam is given. PMID- 27395218 TI - New cockroach species of the genus Panchlora Burmeister (Blaberidae, Panchlorinae) from Ecuador. AB - The genus Panchlora includes 49 species, but only 45 are widely distributed in Central and South America. Most of them are green. The new species herein described presents an ornamental coloration markedly different of all until now described species. Panchlora kozaneki sp. n. is similar to Panchlora pulchella Burmeister, 1838. The number of species known from Ecuador is increased to eight. PMID- 27395219 TI - On the genus Cebrennus Simon, 1880 in Iran with description of a new species from Iranian Central Desert (Araneae: Sparassidae). AB - The taxonomic knowledge on the desert-dwelling sparassid genus Cebrennus Simon, 1880 in Iran is updated by describing a new species, Cebrennus rambodjavani sp. nov. (male) from northern Qom in Iran's Central Desert, and reviewing the material of the previous Iranian record of the genus [sub C. kochi (O. Pickard Cambridge, 1872)] from Bushehr, southern Iran, which is found to be a misidentification. A revised definition of the term "embolus kink", a male copulatory structure in Cebrennus, is given. A comparative discussion of this structure between several representatives of the genus Cebrennus is included. PMID- 27395220 TI - A remarkable new species of Eutrichopoda Townsend, 1908 (Diptera: Tachinidae: Phasiinae). AB - A new Tachinidae species, Eutrichopoda flavipenna sp. nov. (Diptera: Tachinidae: Phasiinae), from Brazil and Paraguay is described and illustrated by photographs and line drawings. The remarkable yellow, feather-like setae on the hind tibia distinguishes the new species from all other species in the tribe Trichopodini. PMID- 27395221 TI - Catalogue and Bibliography of the Hong Kong Carabidae Latreille, 1802 (Coleoptera: Adephaga), with notes on the historic boundaries of Hong Kong as related to zoological collections. AB - A complete list of Carabidae species historically collected in Hong Kong combined with more recent records and notes on their biology is given. Notes on the historic boundaries of Hong Kong through the colonial period are given, as this is an important element relating to our understanding of the origins of historic zoological collections made in the region. Likewise a list of collectors in Hong Kong up to the outbreak of hostilities in the Second World War is given. A full bibliography of Hong Kong Carabidae is included. PMID- 27395222 TI - A new genus and species of cricket from the Chapada Diamantina National Park, northeastern Brazil (Grylloidea: Phalangopsidae; Luzarinae). AB - A new genus and species of Luzarinae cricket (Grylloidea, Phalangopsidae) is described from the Chapada Diamantina National Park, Bahia State, northeast Brazil. Sishiniheia diamantina, n. gen. n. sp. is described based in characters of external morphology and male genitalia and is characterized by the reduced FWs, absence of stridulatory file, thick longitudinal venation and the thin, pointed and curved pseudepiphallic arms. PMID- 27395223 TI - Records of deep-sea anglerfishes (Lophiiformes: Ceratioidei) from Indonesia, with descriptions of three new species. AB - An examination of the ceratioid anglerfishes collected on the Indian Ocean side of Indonesia during surveys in 2004-2005 have revealed 18 species in 9 genera and 6 families, including three new species: Cryptopsaras couesii (Ceratiidae); Melanocetus johnsonii (Melanocetidae); Diceratias trilobus, Bufoceratias microcephalus sp. nov., B. thele, B. shaoi, B. cf. wedli (Diceratiidae); Himantolophus danae, H. sagamius, H. nigricornis, H. macroceratoides (Himantolophidae); Oneirodes quadrinema sp. nov., O. amaokai sp. nov., O. carlsbergi, O. cristatus, Dermatias platynogaster, Chaenophryne cf. melanorhabdus (Oneirodidae); and Linophryne parini (Linophrynidae). Of these, specimens of B. shaoi, H. macroceratoides, O. cristatus and L. parini represent the second records since the species were described. A specimen of H. nigricornis represents the third record and a specimen of Dermatias platynogaster represents the fourth record. Descriptive data and notes on the geographical distribution and morphological variation are provided for each species. PMID- 27395224 TI - Larval morphology of Lebertia insignis Neuman, 1880, L. porosa Thor, 1900 and L. saxonica Thor, 1911 (Acari, Hydrachnidia: Lebertiidae). AB - Illustrated redescriptions of the larvae of the water mite species Lebertia insignis Neuman, 1880, L. porosa Thor, 1900 and L. saxonica Thor, 1911 are presented. The present data suggest that L. saxonica, recently considered as a subspecies or a junior synonym of L. insignis, or as a "species incerta" should be recognized as separate species. A key to all named species based on larvae is given. PMID- 27395225 TI - Agabus abaensis sp. nov., a peculiar species of the confinis-group from central China (Coleoptera: Dytiscidae: Agabinae). AB - Agabus (Acatodes) abaensis sp. nov., from northern Sichuan and south-western Gansu provinces (China) is described and its relevant diagnostic characters are illustrated. The new species is, with some hesitation, classified within the A. confinis species group. Agabus abaensis sp. nov. differs from all species in the group by the combination of the following characters: elytral sculpture with considerably large, distinctly double reticulation in both sexes, and male anterior protarsal claw dentate-the characters resembling some species of the A. arcticus species group. The systematic position of the new species is briefly discussed. PMID- 27395226 TI - Petrocephalus leo, a new species of African electric fish (Osteoglossomorpha: Mormyridae) from the Oubangui River basin (Congo basin). AB - A new species of the African weakly electric fish genus Petrocephalus (Osteoglossomorpha: Mormyridae: Petrocephalinae) is described from the Oubangui (Ubangi) River basin, the principal right-bank tributary of the Congo River. Petrocephalus leo sp. nov. is one of the most distinctive species of Petrocephalus as it combines (among other characteristics) the absence of electroreceptive rosettes on the head with a unique melanin pattern. Only four other species of Petrocephalus lack all electroreceptive rosettes: Petrocephalus microphthalmus, Petrocephalus haullevillii, Petrocephalus schoutedeni, and Petrocephalus zakoni. Petrocephalus leo sp. nov. can be distinguished from these four species in having a distinctive black mark at the base of the pectoral fins (versus absent in P. microphthalmus, P. haullevillii and P. schoutedeni) and no subdorsal black mark (versus present in P. zakoni). A phylogenetic analysis using mitochondrial cytochrome b gene sequences shows haplotypes of P. leo sp. nov. are distinct, but are unexpectedly nested within P. zakoni haplotypes, making this latter species paraphyletic. To investigate this conflict between morphology and mitochondrial cytochrome b, a nuclear marker, the first intron of the gene coding for the S7 ribosomal protein, was sequenced. The presence of four diagnostic indels between P. zakoni and P. leo sp. nov. sequences supports the reciprocal monophyly of these two species. This is the first reported case of conflict between morphology and mitochondrial phylogeny within the genus Petrocephalus. Finally, three species of Petrocephalus are reported for the first time from the Oubangui region bringing the total of Petrocephalus species in this region to 12. PMID- 27395227 TI - Discovery of a new millipede species in northern Vietnam, and the proposal of a new genus, Parariukiaria (Diplopoda, Polydesmida, Xystodesmidae). AB - A survey in Cuc Phuong National Park has revealed the first record of a xystodesmid millipede in Vietnam and also the southernmost locality for the family in Asia. A new genus and species, Parariukiaria cucfuongensis gen. nov, sp. nov. is proposed and described. In addition, three former Riukiaria species from Sichuan Province (China) are reallocated to the new genus, Parariukiaria belousovi (Golovatch, 2014) comb. nov., P. korolevi (Golovatch, 2014) comb. nov., P. kabaki (Golovatch, 2014) comb. nov.. A key to species of the new genus is also provided. PMID- 27395228 TI - Resurrection of Pseudorabdion torquatum (A.M.C. Dumeril, Bibron & A.H.A. Dumeril, 1854), a former synonym of P. longiceps (Cantor, 1847)
(Colubridae: Calamariinae) from Sulawesi, Indonesia. AB - The colubrid snake species Pseudorabdion torquatum is resurrected from the synonymy of P. longiceps. Out of the three syntypes, only two were located and examined at Museum national d'Histoire naturelle, Paris, France (MNHN-RA). Pseudorabdion torquatum differs from P. longiceps in having a larger SVL (227.0 mm vs. 132.0-193.0 mm in males); higher number of ventral in males, 141 (vs. 127 139); lower number of ventrals in females, 137 (vs. 139-145); lower number of subcaudals in both sexes, 12-17 (vs. 17-30); and six supralabials (vs. five). Pseudorabdion torquatum is thus regarded as a valid and endemic species to Sulawesi. The species is here redescribed and a lectotype is designated. Furthermore we provide an English translation of the original description of Rabdion torquatum which was originally written in French. Thus, besides unconfirmed records of P. longiceps from Sulawesi, there is a single known congener from that island, P. sarasinorum. PMID- 27395229 TI - A new species of Paracleistostoma De Man, 1895 (Crustacea: Decapoda: Brachyura: Camptandriidae) from Haikou, Hainan Province, China. AB - A new species of Paracleistostoma De Man, 1895, P. meilanense n. sp. is reported from mangroves forests in Haikou, Hainan Province, China. The new species inhabits mud burrows in the upper intertidal zone and is sympatric with P. tomentosa Yang & Sun, 1993, and P. depressum De Man, 1895. The slender chelipeds as well as the characteristic morphology of the male first pleopod easily distinguishes the species from congeners. PMID- 27395230 TI - The genus Hylaeus Fabricius in Mongolia, an updated species inventory (Hymenoptera: Apoidea, Colletidae). AB - Since the last inventory of Hylaeus species of Mongolia (Dathe 1986a) extensive new collections have been evaluated. An updated checklist of 38 species of Hylaeus so far known from Mongolia is provided, with comments on their biogeographical assignment. Two new species, Hylaeus (Hylaeus) kozlovi sp. n. and Hylaeus (Hylaeus) mellon sp. n., are described. Hylaeus albitarsis Morawitz, 1887 (= H. fuliginosus Warncke, 1972) has been ascertained as a synonym of Hylaeus (Hylaeus) pusillus (Warncke, 1972). The following nine known species are newly recorded from Mongolia: H. (Dentigera) pallidicornis Morawitz, 1876, H. (Hylaeus) aborigensis Dathe, 1994, H. (Hylaeus) angustatus (Schenck, 1861), H. (Hylaeus) fedtschenkoi (Cockerell, 1906), H. (Hylaeus) oblitus (Warncke, 1972), H. (Hylaeus) vulgaris Morawitz, 1876, H. (Lambdopsis) pfankuchi (Alfken, 1919), H. (Nesoprosopis) pectoralis Forster, 1871, H. (Patagiata) nigrocuneatus Cockerell, 1924. PMID- 27395231 TI - Two known and one new species of Draconematidae and Epsilonematida (Nematoda, Desmodorida) from the White Sea, North Russia. AB - Morphological descriptions of three "walking nematode" species found for the first time in the White Sea are presented. Draconema ophicephalum (Claparede, 1863) (Draconematidae) and Epsilonema steineri Chitwood, 1935 (Epsilonematidae), both known from insufficient material and females only, are re-described and problems of their taxonomic identification as well as species compositions of respective genera are discussed. The new species Prochaetosoma marisalbi sp. n. (Draconematidae) differs from other Prochaetosoma species except P. longicapitatum (Allgen, 1935) in that the pharyngeal bulb lumen is not cuticularised, from P. longicapitatum by shape of body and rostrum, greater number of cephalic adhesive tubes, and from P. maertensi Decraemer, 1989 by having a relatively longer tail, fewer anterior adhesive tubes and longer spicules, besides lacking cuticular thickening in the pharyngeal bulb. Draconema hoonsooi, D. youngeouni, P.rochaetosoma beomseomense, P. brevicaudatum, P. byungilli, P. cracense, P. saheungi, P. sujungi, P. supseomense erected by Rho & Min (2011) are considered as invalid species while Prochaetosoma arcticum, P. lugubre and Epsilonema cygnoides are assumed as species inquirenda. From a phylogenetic tree based on the 18S rRNA gene, all three White Sea species adjoin to unidentified species of their respective genera. PMID- 27395232 TI - A new lizard species of the Phymaturus patagonicus group (Squamata: Liolaemini) from northern Patagonia, Neuquen, Argentina. AB - The integrative taxonomy framework allows developing robust hypotheses of species limits based on the integration of results from different data sets and analytical methods. In this work, we test a candidate species hypothesis previously suggested based on molecular data, with geometric and traditional morphometrics analyses (multivariate and univariate). This new lizard species is part of the Phymaturus patagonicus group (payuniae clade) that is distributed in Neuquen and Mendoza provinces (Argentina). Our results showed that Phymaturus rahuensis sp. nov. differs from the other species of the payuniae clade by a higher number of midbody scales, and fewer supralabials scales, finger lamellae and toe lamellae. Also, its multidimensional spaces, both based on continuous lineal variables and geometric morphometrics (shape) characters, do not overlap with those of the other species in this clade. The results of the morphometric and geometric morphometric analyses presented here, coupled with previously published molecular data, represent three independent lines of evidence that support the diagnosis of this new taxon. PMID- 27395233 TI - On three new Orchestina species (Araneae: Oonopidae) described from China. AB - Three new species of oonopid spider from China are diagnosed, described and illustrated: Orchestina apiculata sp. nov. from Hunan, O. bialata sp. nov. and O. multipunctata sp. nov. from Jiangxi. The total number of the known species of Orchestina from China rises to 11 with the addition of three new species described in the present paper. Relationships with Asian and Afrotropical representatives are discussed. PMID- 27395234 TI - Descriptions of three new species of Dzhanokmenia (Hymenoptera: Eulophidae) from China. AB - Three new species of Dzhanokmenia Kostjukov (Hymenoptera: Eulophidae: Tetrastichinae), D. muleica Li, Wang & Hu sp. n., D. karamayica Li, Wang & Zhu sp. n. and D. gobica Li, Wang & Zhu sp. n. from Xinjiang Uyghur Autonomous Region of China are described and illustrated. A key to all known species of the genus is provided. PMID- 27395235 TI - The Dixa inextricata Dyar & Shannon (Diptera: Dixidae) species group, with two new cryptic species from the eastern Nearctic Region. AB - Dixa inextricata Dyar & Shannon is currently regarded as a widespread species in the eastern Nearctic, currently distinguished from sympatric congeners by its brown coloration and triangular gonostylus as seen in lateral view. Recent morphological examination of archival material and dual morphological and molecular examination of recently acquired material fitting the diagnosis of Dixa inextricata revealed the presence of three species. These three species have never been found occupying the same stream in spite of two different pairs of members being geographically and temporally sympatric. The diagnosis of D. inextricata is revised, two closely related species D. appalachiensis sp. nov. and D. calciphila sp. nov., are described and the D. inextricata species group is defined. A key to separate males and natural history data for each species are provided. PMID- 27395236 TI - Review of the genus Pteranabropsis Gorochov, 1988 (Orthoptera: Anostostomatidae: Anabropsinae) with description of two new species from China. AB - This paper describes two new species of the genus Pteranabropsis Gorochov, 1988 (Orthoptera: Anostostomatidae: Anabropsinae) from China, i.e. Pteranabropsis crenatis Song, Bian & Shi sp. nov. and Pteranabropsis incisa Song, Bian & Shi sp. nov. Meanwhile, the photos of important morphological features and a distribution map of the genus Pteranabropsis Gorochov, 1988 are provided. Also, a key to the species of Pteranabropsis is provided. The examined specimens are deposited in the Museum of Hebei University. PMID- 27395237 TI - Larvae and females of two Stenopsyche species in Taiwan with redescription of the male of S. formosana (Insecta: Trichoptera). AB - Larvae and females of two Stenopsyche species, S. formosana Kobayashi and S. drakon Weaver, are described for the first time. They were associated with the adult male through mitochondrial DNA sequence comparisons. The male of S. formosana, which has been recorded as Stenopsyche banksi Mosely from Taiwan, is redescribed. The males of S. formosana and S. banksi can be distinguished from each other by the shape of segments IX and X, and endothecal spines. In larvae, S. formosana and S. drakon are distinguishable from each other and from other known species by the combination of different dark marking patterns and shapes of no. 18 setae of the head, and by the shapes of forecoxae. The larval morphology of S. formosana and S. drakon suggests that the phylogenetic relationships based mainly on male genitalia in the genus Stenopsyche should be reconsidered. PMID- 27395238 TI - The sawfly genus Pleroneura (Hymenoptera, Xyelidae) of Japan: P. itoi n. sp. and a key to species. AB - Pleroneura itoi n. sp. is described from a female specimen collected on Mt. Wasamatayama, Nara prefecture, Honshu, Japan, and a key is given for the four species of Pleroneura from Japan. The new species is well characterized by the richly pale-marked head and the small and slender valvula 3. PMID- 27395239 TI - Three new species of the water strider genus Rhyacobates Esaki, 1923 (Hemiptera: Gerridae) from Vietnam. AB - Three new species: Rhyacobates zetteli sp.n., R. angustus sp.n., and R. constrictus sp.n., all from mountainous areas of northern Vietnam, are described. With these new taxa, a total of six species of Rhyacobates has been recorded from Vietnam. A key to species of Rhyacobates occurring in Vietnam is provided. PMID- 27395240 TI - A new dune-dwelling lizard of the genus Leiocephalus (Iguania, Leiocephalidae) from the Dominican Republic. AB - We describe a new species of Leiocephalus from the coastal dunes of Bahia de las Calderas in the southwestern Dominican Republic. In external morphology, Leiocephalus sixtoi sp. nov. is most similar to L. schreibersii and L. inaguae. Leiocephalus sixtoi differs from L. inaguae in having a U-shaped bony parietal table (vs. V-shaped in L. inaguae), 3 or 4 enlarged postcloacal scales in males (vs. 2 in L. inaguae), most scales on snout posterior to internasal scales rugose to keeled scales (vs. smooth in L. inaguae), and a patternless throat in males, spots on the throat in females (vs. throat with dark streaks and bars in males and females of L. inaguae). Leiocephalus sixtoi differs from L. schreibersii in having the scales of the lateral fold only slightly smaller than adjacent scales (vs. scales of lateral fold distinctly smaller than adjacent scales), having prominent caudal crest scales in adult males (vs. caudal crest scales of moderate size, even in very large males in L. schreibersii), a pattern of dark gray bars on a grayish brown background in the region above the lateral body fold (vs. dense turquoise blue mottling with heavy suffusion of red pigment in L. schreibersii), a darker dorsal ground color (vs. paler in L. schreibersii), and a red iris in adult males (vs. pale grayish blue in adult male L. schreibersii). Leiocephalus sixtoi differs further from L. schreibersii in several osteological characters as follows: in L. sixtoi the nasal process of the premaxilla reaches to mid-level of the bony external nares (vs. to level of posterior margin of the bony external nares in L. schreibersii), lacking a constriction at the base of the nasal process of the premaxilla (vs. such a constriction present in L. schreibersii), and having a reduced nasal-prefrontal contact leaving the nasal processes of the frontal bone exposed (vs. nasal and prefrontal bones contact one another, thereby obscuring the nasal processes of the frontal bone in L. schreibersii). We designate SMF 26228, an adult male from Saint Marc, Province Artibonite, Haiti, as the neotype of L. schreibersii. PMID- 27395241 TI - Platyrhina psomadakisi sp. nov., a new species of fanray (Batoidea: Platyrhinidae) from the Andaman Sea, the first record of this family in the Indian Ocean. AB - A new species of fanray (Platyrhina) is described based on four specimens collected in 2015 from the Andaman Sea, off Myanmar. These represent the first records of the family Platyrhinidae from the Indian Ocean with the three other members of the genus being restricted to the North-West Pacific. The new species differs from its congeners in having a series of faint dark bands on the body and tail, more pectoral-fin radials, and much more widely separated dorsal fins. PMID- 27395242 TI - A new species of Dudgeodes Sartori, 2008 (Ephemeroptera: Teloganodidae) from Thailand. AB - A new species of the genus Dudgeodes Sartori, 2008 is described from Thailand. It is the first representative of the genus reported from this country. The species is described based on mature nymphs. Dudgeodes romani sp. nov. differs from other species of the genus by the length of antennae; coloration of male eyes; shape of abdominal median tubercles; features of the tarsal claws, forefemora, gills and segments of the labial palps, and by chaetotaxy. PMID- 27395243 TI - New Geranomyia crane flies (Diptera: Limoniidae) from Korea and Kunashir Island. AB - Geranomyia kunashir n. sp. from Kunashir Island (Far East of Russia), Geranomyia piagola n. sp. and Geranomyia semjina n. sp. from South Korea are described. Keys for all species of Korean Geranomyia are presented. PMID- 27395244 TI - Description of a new species of Gaeolaelaps (Acari: Laelapidae) from Iran, with a key to world species of the genus with short peritremes. AB - A new species of Gaeolaelaps (Acari, Mesostigmata, Laelapidae) is described based on morphological characters of adult females collected from nest of Formica sp. (Hymenoptera: Formicidae) in the Shahrekord Region, Chaharmahal va Bakhtiari province, Iran. A key for the identification of species of Gaeolaelaps with short peritremes is presented. PMID- 27395245 TI - Re-description of Echiniscus cavagnaroi Schuster & Grigarick, 1966 (Tardigrada: Heterotardigrada: Echiniscoidea: Echiniscidae) from type material, with new records from Hawaii and Bermuda. AB - The description of Echiniscus cavagnaroi Schuster & Grigarick, 1966 (Tardigrada: Heterotardigrada: Echiniscoidea: Echiniscidae) is emended with new morphometric measurements of the holotype and eleven paratypes. The length of Cirrus A in the holotype (25.2 MUm) was only half the 50 MUm reported in the original description. Moreover, the largest values for Cirrus A length and Cirrus A to body length ratio for any specimen (40.6 MUm, 21%) were also lower than in the original description. Variation in the presence or absence of spines was considerably greater than originally described. Spines C, Dd and E were not present on all specimens (C present in 67%, Dd in 67%, E in 50%). The length of spines Dd and E, when present, varied greatly among specimens. The geographical range of E. cavagnaroi is expanded by new records from the Hawaiian Islands and Bermuda. The species has been reported from southern China; however, the published description of these specimens differs markedly from type specimens in several respects. The presence of E. cavagnaroi sensu stricto in China needs to be confirmed. The high variability in presence or absence and length of spines in Echiniscus cavagnaroi underscores the importance of assessing variability in these characteristics when identifying unknown specimens or describing new species in the genus. This requires using as many specimens as possible and fully reporting variability. PMID- 27395246 TI - Description of the puparium and redescription of the imagoes of Chorophthalmyia brevicornis Lindner (Diptera: Stratiomyidae). AB - The puparium of Chorophthalmyia brevicornis is described for the first time, based on five puparia. Larvae of the species were reared in the laboratory under semi-controlled conditions until the emergence of the adults. In addition, to the description of the puparium we provide a redescription of the imagoes of C. brevicornis. PMID- 27395247 TI - Two new dwarfgobies from the Indian and Western Pacific Oceans (Teleostei: Gobiidae: Eviota). AB - Two new species of dwarfgobies are described, Eviota asymbasia from the Sulu Sea, Philippine Islands, south to Java and west to Damar, and E. bipunctata occurring from the Indian Ocean eastward into the western Pacific Ocean. Eviota asymbasia lacks the IT pore of the cephalic sensory-pore system and usually also the POP, has a dorsal/anal-fin formula of 8/8, has some pectoral-fin rays branched and usually 15 rays, two spots on the pectoral-fin base, no dark spot over the preural centrum, first dorsal fin may be filamentous, six ventral postanal spots, and the male genital papilla is not fimbriate. Eviota bipunctata belongs to the group with cephalic sensory-pore system pattern 2 (lacking only the IT pore), some pectoral-fin rays branched, pectoral-fin base with 1 or 2 prominent dark spots, dorsal/anal-fin formula usually 8/8, and no occipital spots. PMID- 27395248 TI - Erratum: ALLEN F. SANBORN (2016) The cicada genus Guyalna Boulard & Martinelli, 1996 (Hemiptera: Cicadidae: Cicadinae: Fidicinini): generic description, twelve new combinations, and a key to species. Zootaxa, 4105 (5): 430-454. PMID- 27395249 TI - Catalogue of Diptera of Colombia (Title page). PMID- 27395251 TI - Catalogue of Diptera of Colombia: an introduction. AB - Colombia has an imposing natural wealth due to its topography has many unique characteristics as a consequence of having Caribbean and Pacific shores, as well as sharing part of the Amazon basin and northern Andes mountains. Thus, many natural and biological features are due to the convergence of three biogeographical regions: Pacific, Andes and Amazonia. The Andean uplift created a complex mosaic of mountains and isolated valleys, including eleven biogeographical provinces (Morrone 2006). The Andes dominate the Colombian topography and cross the country south to north. There are three mountain ranges (Western, Central, and Eastern) with a maximum elevation of 5,775 m, and an average elevation of 2,000 m. The Magdalena and Cauca River valleys separate these ranges, that along with the Putumayo and Caqueta Rivers, the Catatumbo watershed, the Darien, Pique Hill, the Orinoquia Region (with its savannas), the Amazon region (with tropical rainforests), and some lower mountain ranges (Macarena and Chiribiquete), have generated the conditions for very high levels of endemism. This variety of conditions has resulted in an extremely diverse plant and animal biota, and in which 48% of the nation remains unexplored. PMID- 27395252 TI - FAMILY ANISOPODIDAE. AB - This considerably small family is poorly known in Colombia, with only two species reported for the genus Sylvicola Harris (1776) so far. We synonymize Neomesochria Amorim & Tozoni (1994) to Mycetobia Meigen (1818), hence transferring the Dominican amber species Neomesochria antillea (Grimaldi 1991) and N. cryptambra (Grimaldi 1991), and the recent Neotropical species N. limanda (Stone 1966) and N. stonei (Lane & d'Andretta 1958) back to the genus Mycetobia. This paper provides new records for Mycetobia and Olbiogaster Osten-Sacken (1886) for Colombia. PMID- 27395253 TI - FAMILY BIBIONIDAE. AB - The Bibionidae are a family belonging to the suborder Bibionomorpha with four genera and 17 species known from Colombia. This work expands the distribution of these species to other localities in the country. PMID- 27395254 TI - FAMILY CECIDOMYIIDAE. AB - This large family is poorly known in Colombia, where only 44 species have been recorded in 20 genera. All of them are included in Cecidomyiinae, which is the most diverse subfamily of gall midges in number of species and feeding habits, including phytophagous, predaceous and fungivorous species. Most of them are galler. The other subfamilies have never been recorded in this country. PMID- 27395255 TI - FAMILY SCIARIDAE. AB - Sciaridae are a widely distributed family with high number of species. They are known as black fungus gnats due to their dark color and feeding activity. This catalogue presents 17 species from Colombia distributed in eight genera, and for each species the geographical distribution is provided. PMID- 27395256 TI - FAMILY RANGOMARAMIDAE. AB - This small family of Diptera is poorly known in Colombia. In the present catalogue, we feature a single report for the country, of a species of the genus Eratomyia. PMID- 27395257 TI - FAMILY DITOMYIIDAE. AB - The Ditomyiidae are a family belonging to the suborder Bibionomorpha, until now without records to Colombia. This work reports the first record of the genera Rhipidita and Calliceratomyia for the Colombian region. PMID- 27395258 TI - FAMILY DIADOCIDIIDAE. AB - Diadocidiidae are a small family belonging to the suborder Bibionomorpha. Three species were described for the Neotropical region, two from Costa Rica and one from Brazil, and one additional undescribed species from Colombia is reported here for the first time. PMID- 27395259 TI - FAMILY KEROPLATIDAE. AB - Currently, 86 genera are ascribed to the Keroplatidae, with about 950 known species. The family includes three subfamilies: Arachnocampinae, Macrocerinae, and Keroplatinae. Both Macrocerinae and Keroplatinae are found in Colombia, with five described species distributed in four genera. The available information about Colombian keroplatids is compiled, with new records for five genera. PMID- 27395260 TI - FAMILY LYGISTORRHINIDAE. AB - The Lygistorrhinidae are a family belonging to the suborder Bibionomorpha, with no previous record from Colombia. This paper refers for the first time to the occurrence of the family in the country, an undetermined species of the genus Lygistorrhina (Probolaeus) Williston. PMID- 27395262 TI - FAMILIES TIPULIDAE AND LIMONIIDAE. AB - A catalogue of the Colombian crane flies (Tipulomorpha, families Tipulidae and Limoniidae) is provided, based on updated information from the Catalogue of the Crane flies of World, with additional data on the geographical distribution of the species in Colombia taken from the primary literature. A total of 131 valid species are recorded for Colombia, 38 in the family Tipulidae and 93 in the family Limoniidae. PMID- 27395261 TI - FAMILY MYCETOPHILIDAE. AB - The Mycetophilidae include small fungus-gnats which life cycle is associated with fungi, especially of the larvae. The known diversity of the family in the Neotropical region is 1,145 species, but only some very few papers have been published on the Colombian species of Mycetophilidae, with records for the genera Docosia Winnertz, Paraleia Tonnoir, and Dziedzickia Johannsen. This catalogue gathers the information available on mycetophilids from Colombia, including genera and some species that for the first time are mentioned to occur in the country-as Leiella unicincta Edwards and Leiella zonalis Edwards. PMID- 27395263 TI - FAMILY CERATOPOGONIDAE. AB - Two hundred and thirty five species of Ceratopogonids arranged in 28 genera are listed for Colombia, mostly Culicoides (112 species) and Forcipomyia (50 species). For each listed species, information on type locality, type category and sex, location of type material, species distribution, localities for Colombia and main references, is provided. Localities are not specified for 17 species in which the literature searching was negative. Forcipomyia squamitibia Lutz and Bezzia clavipennis are excluded from the list. PMID- 27395265 TI - FAMILY SIMULIIDAE. AB - This catalogue presents 70 species distributed in two genera for Colombia: Gigantodax with 5 groups, and Simulium with 6 subgenera and 17 groups. Three species are recorded for the first time: Gigantodax vulcanius, G. gracilis, and Simulium pautense, and the distributional range is expanded to S.ochraceum, S. paynei, S. metallicum, and S. callidum. PMID- 27395264 TI - FAMILY CHIRONOMIDAE. AB - Only 30 chironomid species distributed in 16 genera and three subfamilies are formally recorded to Colombia. Another 32 genera and two subfamilies have been recorded on larval stage, with no identification at species level. Many new records, genera and species are expected when focusing on systematics of chironomids from Colombia. PMID- 27395266 TI - FAMILY CORETHRELLIDAE. AB - Corethrellidae are poorly known in Colombia, with few specimens deposited in collections, and only nine named species of Corethrella Coquillett are reported for the country. An additional six undescribed species have been recently collected, indicating that the number of recorded species in Colombia is underestimated. PMID- 27395267 TI - FAMILY BLEPHARICERIDAE. AB - Blephariceridae are poorly known in Colombia, being reasonably well sampled only in Antioquia Department. In the present catalogue, five species of Limonicola Lutz and eight species of Paltostoma Schiner are reported for the country. PMID- 27395268 TI - FAMILY PSYCHODIDAE. AB - A catalogue is presented of the species of haematophagous and non-haematophagous psychodids recorded in Colombia. The list comprises 199 species distributed among five subfamilies and 16 genera, as follows: Subfamily Bruchomyiinae, genus Nemopalpus Macquart, 1838 (4 species); subfamily Phlebotominae, genera Brumptomyia Franca & Parrot, 1921 (8 species), Lutzomyia Franca, 1924 (153 species) and Warileya Hertig, 1948 (2 species); subfamily Psychodinae, genera Arisemus Satchell, 1955 (3 species), Australopericoma Vaillant, 1975 (1 species), Balbagathis Quate, 1996 (1 species), Clogmia Enderlein, 1937 (1 species), Didicrum Enderlein, 1937 (1 species), Feuerborniella Vaillant, 1971 (1 species), Lepidiella Enderlein, 1937 (1 species), Maruina Muller, 1895 (4 species), Paramormia Enderlein, 1935 (1 species), Parasetomima Duckhouse, 1968 (1 species) and Psychoda Latreille, 1796 (7 species); subfamily Sycoracinae, genus Sycorax Haliday, 1839 (5 species); and subfamily Trichomyiinae, genus Trichomyia Haliday, 1839 (5 species). PMID- 27395269 TI - FAMILY SCATOPSIDAE. AB - An updated catalogue of the family Scatopsidae in Colombia is presented. Seven species of six genera have being recorded for the country, but four of these species are still undescribed. The Ectaetiinae genus Ectaetia, the Psectrosciarinae genera Anapausis and Psectrosciara, and at least the Scatopsinae genera Scatopse, Efcookella, and Abrhexoza are expected to be present in the fauna of the family in Colombia. PMID- 27395270 TI - FAMILY RHAGIONIDAE. AB - The family Rhagionidae is one of the oldest Brachyeran lineages. Its monophyly is still uncertain. There are four rhagionid genera distributed in Neotropical Region but only three species of Chrysopilus are found in Colombia. PMID- 27395271 TI - FAMILY TABANIDAE. AB - This catalogue presents 256 species distributed in 32 genera, six tribes and three subfamilies recorded to Colombia. For each species we present the available geographical information and most important references. PMID- 27395272 TI - FAMILY XYLOPHAGIDAE. AB - This family is recorded for the first time to Colombia, with only one undescribed species of genus Rachicerus. PMID- 27395273 TI - FAMILY PANTOPHTHALMIDAE. AB - This catalogue features 11 species distributed in 2 genera recorded to Colombia. Three species of Pantophthalmus are recorded for the first time to the country. PMID- 27395274 TI - FAMILY STRATIOMYIDAE. AB - The family Stratiomyidae has more than 2,800 described species, of which 1001 species belongs to the Neotropics. This catalog for Colombia presents 87 species distributed in 32 genera, and ten subfamilies. Merosargus gracilis and the genus Microchrysa, with a single species M. bicolor are recorded for the first time to Colombia. The fauna is very expressive but still poorly known, representing nearly one tenth of the Neotropical diversity of the family in numbers of species, and one fifth of generic diversity. PMID- 27395275 TI - FAMILY XYLOMYIDAE. AB - This family is poor known in Colombia with only two known species of two genera, Solva tuberculata and Arthropeina colombiana. PMID- 27395276 TI - FAMILY ACROCERIDAE. AB - A catalog of the Acroceridae from Colombia is provided. Five species and five genera are recorded for the country, including one undescribed Ocnaea species. PMID- 27395277 TI - FAMILY NEMESTRINIDAE. AB - Nemestrinidae (Diptera, Nemestrinoidea) are a relatively rare group of flies, and the knowledge on the Colombian fauna is still incipient. According to the available literature, only one species is recorded to this country, Hyrmophlaeba magdalena Bernardi, 1977. PMID- 27395278 TI - FAMILY ASILIDAE. AB - Asilidae is one of the largest Diptera families with more than 7,000 recognized species worldwide. All their species are predators on arthropods, mainly insects. This catalogue presents 71 species distributed in 26 genera, ten tribes or generic groups and four subfamilies. For each species we present the available geographical information and relevant references. PMID- 27395279 TI - FAMILY BOMBYLIIDAE. AB - Bombyliidae is one of the largest Diptera families with more than 4,500 recognized species worldwide. Their species vary from robust to thin, and may be small to large (2-20mm) and looks like bees or wasps. They also present great variation in color. Adults can often be seen either resting and sunning themselves on trails, rocks or twigs or feeding on flowering plants as they are nectar feeders. All reared bee flies are predators or parasitoids of arthropods. The Colombian fauna of bombyliids comprises at the moment 22 species, and 12 genera, of which, six are endemic species. Nonetheless, this number may be much higher, as Colombia is a megadiverse country and there are not many specimens of this family deposited in collections all over the world. PMID- 27395280 TI - FAMILY MYDIDAE. AB - Mydidae (Diptera, Asiloidea) are a relatively rare group of flies, and the knowledge on the Colombian mydids is very poor. According to available literature, only two species are registered to this country, Protomydas coerulescens (Olivier, 1811) and P. rubidapex (Wiedemann, 1830). PMID- 27395281 TI - FAMILY THEREVIDAE. AB - This catalogue presents the Colombian fauna of stiletto flies (Diptera: Therevidae). According to available literature, only four species, distributed in three genera, are registered to this country, Ataenogera brevicornis (Bromley, 1934), Brachylinga punctifrons (Krober, 1914), B. xanthoperna Irwin and Webb, 1991 and Chromolepida pruinosa (Coquillett, 1904). PMID- 27395282 TI - FAMILY EMPIDIDAE. AB - Empididae is one of the biggest families of Diptera with around 3,000 known species. The family is poorly known in Colombia, with only six species reported and this work provides information on their distribution. No endemic genera or species have been recorded to date from Colombia. PMID- 27395283 TI - FAMILY HYBOTIDAE. AB - Hybotidae is a diverse family of the order Diptera, suborder Brachycera, superfamily Empidoidea. Hybotid flies are generally yellow to black, are morphologically diverse, and are distributed worldwide. The monophyly of the family is based on: palpifer and fore tibial gland present, laterotergite bare and R4+5 unbranched. Hybotids are mainly predators and are usually found on the vegetation, logs and other surfaces, or in flight during displacement and forage. This catalogue, based on the study of specimens and available literature records, summarizes and updates the information on the Colombian fauna of Hybotidae, which includes 19 species distributed in six genera. PMID- 27395284 TI - FAMILY DOLICHOPODIDAE. AB - The Dolichopodidae recorded from Colombia are listed based on literature data only and currently comprise 30 species in 14 genera (six subfamilies). Information on type material and depository institutions is given. PMID- 27395285 TI - FAMILY PHORIDAE. AB - The Phoridae recorded from Colombia are catalogued, totaling 226 species distributed in 19 genera and three subfamilies. For each species, distribution, hierarchic position and cited references are presented. PMID- 27395286 TI - FAMILY PIPUNCULIDAE. AB - Pipunculidae presently have around 1,400 known species, but it is poorly known in Colombia, with only ten reported species in all territory. The genera Eudorylas Aczel and Tomosvaryella Aczel are the most abundant. This work provides information on the species distribution. No endemic genera have been recorded to date from Colombia. PMID- 27395287 TI - FAMILY SYRPHIDAE. AB - This paper is an updated Catalogue of Syrphidae from Colombia, including 337 species belonging to 3 subfamilies, 11 tribes, 57 genera and 16 subgenera. Each species is listed under its current accepted taxon, including the original reference, type locality, distribution by state/province in Colombia, in addition to a complete bibliographic reference. Species in the genera Calostigma, Claraplumula, Eristalinus, Fazia, Hermesomyia, Hybobathus, Mimocalla, Menidon, Monoceromyia, Orphnabaccha, Pelecinobaccha, Peradon, Rhinoprosopa, Sphiximorpha and Styxia are listed for the first time from Colombia. The advance in the knowledge of the Colombian Syrphidae is briefly discussed. PMID- 27395288 TI - FAMILY MICROPEZIDAE. AB - Sixty species and 14 genera of Micropezidae are recorded from Colombia, including four species of Micropezinae and 56 species of Taeniapterinae. The following species are newly recorded from the country: Grallipeza affinis, G. ecuadoriensis, G. obscura, G. nigrinotata, G. pseudosimplex, Ptilosphen comis, P. conveniens, P. enderleni, P. facetus and P. mimicus. PMID- 27395289 TI - FAMILY NERIIDAE. AB - Here we provide a catalog of the Neriidae from Colombia, with all six genera and 17 species in alphabetical order. With each genus we provide references and with each species we include the original name, type-locality, acronym of the institution where the type is deposited and the known geographical distribution. In the case of samples only from Colombia, we provide additional details for locality, relevant synonymy and additional references. PMID- 27395290 TI - FAMILY TANYPEZIDAE. AB - The Tanypezidae of Colombia are catalogued. Nine species in one genus are presented and geographical information are provided for all species, when available. PMID- 27395291 TI - FAMILY SYRINGOGASTRIDAE. AB - This catalog features the three species of Syringogastridae that have been reported for Colombia. It is entirely based on literature data and contains no new records. PMID- 27395292 TI - FAMILY CONOPIDAE. AB - A catalogue of the Conopidae known from Colombia, with 16 species distributed in four genera, is presented. The richest group is Stylogaster Macquart. Geographic distributions are given for each species. PMID- 27395293 TI - FAMILY LONCHAEIDAE. AB - This family was poorly known in the Neotropical region, mainly in Colombia. However, recent studies increased its knowledge with new distribution records. This catalogue presents 44 species distributed in three genera. PMID- 27395294 TI - FAMILY PIOPHILIDAE. AB - Piophilidae is a little family poorly known in Colombia, with only Piophila casei (L.) and Stearibia nigriceps Meigen reported so far. This catalogue expands the distribution of these species to other localities in the country. PMID- 27395295 TI - FAMILY PLATYSTOMATIDAE. AB - Platystomatidae (Signal Flies) are one of the largest families of Tephritoidea, with about 1200 species and four subfamilies, worldwide distributed. However, Platystomatidae are not well represented in the New World, and in the Neotropical Region only four genera and 26 species, belonging to Platystomatinae, are recorded. The family is a group understudied in Colombia and only one species is recorded to the country. PMID- 27395296 TI - FAMILY PYRGOTIDAE. AB - Pyrgotidae is a family of endoparasitics flies of beetles with worldwide distribution. The Neotropical fauna is composed by 59 valid species names disposed in 13 genera. The occurrence of Pyrgota longipes Hendel is the first record of the family in Colombia. PMID- 27395297 TI - FAMILY RICHARDIIDAE. AB - Richardiidae are a family of "acalyptrate" Diptera represented by ca. 180 species distributed in the New World, mostly in the Neotropical region. The species that occur in Colombia have received little attention from taxonomists, and the great majority of them are known only from their type localities. Currently, 14 genera and 23 species are known to occur in the country. PMID- 27395298 TI - FAMILY TEPHRITIDAE. AB - The present Catalogue includes 90 species and 23 genera of Tephritidae that have been recorded in Colombia. Four subfamilies (Blepharoneurinae, Dacinae, Trypetinae and Tephritinae), and eight tribes (Acrotaeniini, Carpomyini, Dacini, Eutretini, Myopitini, Noeetini, Tephritini, and Toxotrypanini) are represented in the Colombian territory. The species Toxotrypana littoralis and Tomoplagia pleuralis are new records for the country. Trypeta conferta Walker, 1853 is here formally transferred to the genus Neomyopites. PMID- 27395299 TI - FAMILY LAUXANIIDAE. AB - An updated Catalogue of the Lauxaniidae of Colombia is presented. This acalyptratae family is poorly known in Colombia, with only 36 described species in 33 genera. This paper expands the distribution of 24 species to Colombia. At total, 63 species are reported here for Colombia. PMID- 27395300 TI - FAMILY ROPALOMERIDAE. AB - Ropalomeridae is a small family with most species distributed in the Neotropical Region, from Mexico to Argentina, and only one Nearctic species. In Colombia, eight species distributed in four genera have been found. This catalogue, based on the study of specimens and available literature records, summarizes and updates the information on the Colombian fauna. PMID- 27395301 TI - FAMILY SCIOMYZIDAE. AB - The Sciomyzidae are a family of acalyptrate flies of worldwide distribution, with 543 extant species and 14 described subspecies in 63 genera. Although 274 species in 37 genera are found in the Western Hemisphere, the sciomyzid fauna of Central and South America remains relatively unknown, comprising 103 species in 25 genera, with only seven species in five genera having been recorded from Colombia: Dictya bergi Valley, Perilimnia albifacies Becker, Pherbellia guttata (Coquillett), Sepedomerus bipuncticeps (Malloch), S. macropus (Walker), Sepedonea guianica (Steyskal), and S. isthmi (Steyskal). PMID- 27395302 TI - FAMILY SEPSIDAE. AB - An updated Catalogue of the Sepsidae of Colombia is presented. This small acalyptratae family is poorly known in Colombia, with only ten reported species in four genera. PMID- 27395303 TI - FAMILY CLUSIIDAE. AB - Here we catalogued 23 species in two genera of Clusiidae from Colombia. For each species the available geographical information is presented. PMID- 27395304 TI - FAMILY AGROMYZIDAE. AB - Agromyzidae are a family with many species described throughout the world. The family is known as leaf-miner flies, for the phytophagous habits of their larvae, feeding within plant tissues. This catalogue presents 74 species recorded from Colombia, distributed in 12 genera and two subfamilies. For each species we present the available geographical distribution in the country. PMID- 27395305 TI - FAMILY PERISCELIDIDAE. AB - This catalog summarizes information on the three species of Periscelididae known to occur in Colombia. One species belongs to the subfamily Periscelidinae, and two to the Stenomicrinae. This catalog includes no new record for Colombia. PMID- 27395306 TI - FAMILY AULACIGASTRIDAE. AB - This catalog features the only species of Aulacigastridae recorded for Colombia, Aulacigaster grimaldii Rung & Mathis, 2012. PMID- 27395307 TI - FAMILY SPHAEROCERIDAE. AB - This catalog compiles information on the 13 genera and 25 species of Sphaeroceridae that have been reported for Colombia. It is entirely based on literature data and no new records are presented. PMID- 27395308 TI - FAMILY CHLOROPIDAE. AB - The Chloropidae representatives from Colombia are poorly known, and are represented by one Shiphonellopsinae genus, five Chloropinae genera and 19 Oscinellinae genera, in a total of 46 described species. PMID- 27395309 TI - FAMILY MILICHIIDAE. AB - This catalog summarizes information on the species of Milichiidae known to occur in Colombia. It includes 6 described species in 3 described genera and 6 undescribed species in two genera, one of which is also undescribed. PMID- 27395310 TI - FAMILY CURTONOTIDAE. AB - The family Curtonotidae is represented in the New World only by the genus Curtonotum Macquart. This catalogue presents the three species of Curtonotum recorded from Colombia: C. bivittatum Klymko & Marshall, C. trypetipenne Hendel and C. tumidum (Enderlein). PMID- 27395311 TI - FAMILY DROSOPHILIDAE. AB - This catalogue presents 176 species distributed in 17 genera and four tribes of Drosophilidae in Colombia, with both subfamilies, Drosophilinae and Steganinae, represented in the Colombian territory. This is probably an underestimate of the real richness of drosophilid species in the country, for two reasons. First, there are relatively few collections of Drosophilidae in Colombia, resulting in significant spatial gaps in the sampling of these flies. Second, we have not considered here species that have already been recorded in neighbour countries but not in Colombia. Consequently, there are certainly several described species, as well as new species, that occur in this area but are not listed here. We hope that this catalogue will stimulate new inventories of drosophilids in Colombia, contributing to fill gaps in the knowledge of this family of flies in the country. PMID- 27395312 TI - FAMILY EPHYDRIDAE. AB - This catalog presents 53 species of Ephydridae from Colombia that are classified into five subfamilies, 15 tribes and 26 genera. For each species we present the available geographical information. PMID- 27395313 TI - FAMILY HIPPOBOSCIDAE. AB - This catalog presents 18 species distributed among 11 genera and two subfamilies of hippoboscid flies recorded in Colombia. For each genus we present synonymies and type species, and for each species account we present synonymies, disposition of type material, and specific localities, departments and, when available, the type-host. PMID- 27395314 TI - FAMILY NYCTERIBIIDAE. AB - This catalog presents eight species distributed among two genera and one subfamily of nycteribiid bat flies recorded in Colombia. For each genus we present synonymies and type species, and for each species account we present synonymies, disposition of type material, and specific localities and departments. PMID- 27395315 TI - FAMILY STREBLIDAE. AB - This catalog presents 73 species distributed among 19 genera and three subfamilies of streblid bat flies recorded in Colombia. For each genus we present synonymies and type species, and for each species account we present synonymies, type host, disposition of type material, and specific localities and departments for records known from Colombia. PMID- 27395316 TI - FAMILY ANTHOMYIIDAE. AB - Here we catalogue six species in four genera of Anthomyiidae (Anthomyia, Calythea, Delia, and Emmesomyia) from Colombia and provide geographical information for all species, when available. PMID- 27395317 TI - FAMILY FANNIIDAE. AB - Here we catalogue 32 species in two genera of Fanniidae (Euryomma and Fannia) from Colombia and provide geographical information for all species, when available. PMID- 27395318 TI - FAMILY MUSCIDAE. AB - The Muscidae species in Colombia are first catalogued. 108 species and 41 genera are reported to the country, added with 14 new species not yet described in Agenamyia, Apsil, Drymeia, Graphomya and Reinwardtia genera. There are 15 new species records to Colombia. References are given to the original descriptions and taxonomic, biological, and applied literature made for Colombia. PMID- 27395319 TI - FAMILY SCATHOPHAGIDAE. AB - Scathophagidae (Diptera, Calyptratae) is an uncommon group of flies. In Colombia there was no scientific record of this family until now. In this paper we report for the first time the genus Scatogera and the species S. primogenita Albuquerque, collected over 3000m. and previously collected in Ecuador. PMID- 27395320 TI - FAMILIES CALLIPHORIDAE AND MESEMBRINELLIDAE. AB - Calliphoridae and Mesembrinellidae (Diptera, Oestroidea) are very common groups of flies, the Calliphoridae with worldwide distribution and over 1,000 described species, while the Mesembrinellidae are restricted to the Neotropical Region and founded mainly in areas with undisturbed native vegetation. This catalogue presents two families: Calliphoridae, with 4 subfamilies, 31 species distributed in 12 genera, and Mesembrinellidae, with 7 genera and 21 species. PMID- 27395321 TI - FAMILY OESTRIDAE. AB - The Oestridae of Colombia are poorly known. There are reports only for the genera Cuterebra, Dermatobia and Metacuterebra and three species, one species per genera. PMID- 27395322 TI - FAMILY RHINOPHORIDAE. AB - Only one species of Rhinophoridae has been recorded to Colombia so far, Bezzimyia busckii Townsend, 1919. However, three other species of the genus Bezzimyia are listed in the present catalogue, for they occur on nearby areas and are likely to occur in the country as well. PMID- 27395323 TI - FAMILY SARCOPHAGIDAE. AB - A catalogue of Sarcophagidae recorded from Colombia is presented, including 102 species in 26 genera, and two subfamilies. The geographical distribution by department is also given. PMID- 27395324 TI - FAMILY TACHINIDAE. AB - The present catalogue summarizes 154 species and 71 genera occurring in Colombia. All the four subfamilies (Phasiinae, Dexiinae, Tachininae and Exoristinae), and 24 tribes are represented in the Colombian territory. PMID- 27395325 TI - Myeloid Sarcoma Presenting as Low Back Pain in the Pediatric Emergency Department. AB - BACKGROUND: Low back pain is a common symptom in the pediatric population; approximately half of all children present with at least one episode of low back pain. The majority of cases are due to nonspecific causes such as musculoskeletal trauma with spontaneous regression. On some occasions, however, life-threatening diseases have to be considered. CASE REPORT: A 15-year-old girl presented to the Pediatric Emergency Department for a history of continuous 2-day duration of low back pain and transient paresthesia of the right gluteal area. Low back pain was diagnosed and nonsteroidal anti-inflammatory treatment combined with rest were prescribed. After 7 days, worsening of the clinical conditions was observed with bilateral gluteus paresthesia. A corset was recommended, and magnetic resonance imaging (MRI) and rheumatological evaluation were prescribed on an outpatient basis. After 5 days she was hospitalized due to urinary incontinence and persistence of pain. Blood tests revealed neutrophil leukocytosis associated with mild anemia, thrombocytopenia, hyperuricemia, and increased lactate dehydrogenase. MRI examination of the spine demonstrated a mass involving the sacral canal and the presacral region, extending through the sacral foramina, along the nerve roots. Similar tissue was found at multiple levels in the spine and in the right orbit. Bone marrow aspiration and biopsy highlighted the presence of myeloid blasts and myeloid dysplasia, consequently, myeloid sarcoma was diagnosed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case demonstrates the importance of prompt identification of diagnostic "red flags" in childhood low back pain, indicating the need for diagnostic investigations such as MRI and blood tests. PMID- 27395326 TI - Changes over time in the prevalence of asthma, rhinitis and atopic eczema in adolescents from Taubate, Sao Paulo, Brazil (2005-2012): Relationship with living near a heavily travelled highway. AB - BACKGROUND: The prevalence of allergic diseases is increasing. We evaluated temporal trends in the prevalence of asthma, rhinitis and eczema in adolescents (13-14 years) living in Taubate, SP, Brazil (2005-2012) and assessed the relationship between these prevalences and the residential proximity to Presidente Dutra Highway (PDH, a heavily travelled highway). METHODS: This cross sectional study of adolescents (N=1039) from public and private schools was evaluated using the standard questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) plus a question about their place of residence in relation to PDH. The data obtained were compared to the 2005 data using a chi square test or Fisher's exact test. An analysis by groups consisting of two phases (two-step cluster) was used to evaluate the effect of living near PDH. RESULTS: There was a lifetime increase in the prevalence of active asthma (15.3% vs. 20.4%, p=0.005) and physician-diagnosed asthma (6.8% vs. 9.2%, p=0.06) and a decrease in the symptoms of active rhinitis (36.6% vs. 18.5%) between 2005 and 2012. A high frequency of asthma and rhinitis (18.1% vs. 23.2%, respectively) was observed among adolescents living close or very close to PDH; furthermore, 85.6% of the adolescents without symptoms of asthma or rhinitis lived far from PDH. CONCLUSION: An increase in the prevalence of asthma and a decrease in the prevalence of rhinitis were observed during the studied period. Living near PDH was associated with higher rates of asthma, rhinitis, and eczema. PMID- 27395328 TI - Nutrient patterns and chronic inflammation in a cohort of community dwelling middle-aged men. AB - BACKGROUND & AIMS: There is limited data relating to the effect of the combination of nutrients on inflammation and the interactions with lifestyle factors and chronic conditions. We examined the association between nutrient patterns and inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL 6) in community dwelling middle-aged and elderly Australian men. METHODS: Participants (mean age 59.7 y) with complete data relating to diet and fasting serum inflammatory markers in the Men Androgen Inflammation Lifestyle Environment and Stress cohort were analysed (n = 1577 for CRP, n = 1557 for IL-6). Food intake was assessed using a food frequency questionnaire, and nutrient patterns were identified by factor analysis. Biomedical examinations were conducted in The Queen Elizabeth Hospital and Lyell McEwin Health Service. CRP and IL-6 were log transformed due to the skewed distribution. Linear regression models were used to assess the association between nutrient patterns and inflammation. RESULTS: We generated three nutrient patterns by factor analysis. An animal-sourced pattern (animal protein, cobalamin, cholesterol and omega-6) was positively associated with CRP (p for trend across quartiles 0.057). A plant-sourced pattern (beta carotene, vitamin A, lutein and zeaxanthin) was inversely associated with CRP (p for trend across quartiles 0.005). The association between plant-sourced pattern and CRP was stronger in participants with severe sleep apnoea, smoking (p for interaction 0.019), and participants without diabetes (p for interaction 0.238) and/or with normal triglycerides (p for interaction 0.005) and high density lipoprotein (p for interaction 0.120) compared with their counterparts. No interactions were found between the animal-sourced pattern and lifestyle factors and chronic conditions. No independent associations were found between the animal/plant-sourced pattern and IL-6. No associations were found between the vitamin B and folate pattern (total folate, thiamine, riboflavin and niacin) and inflammatory markers. CONCLUSIONS: While an animal-sourced pattern may enhance inflammation level, a plant-sourced pattern may reduce inflammation particularly in people with less healthy lifestyles and severe obstructive apnoea. PMID- 27395329 TI - Feeding the brain - The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials. AB - BACKGROUND & AIMS: Micronutrients are essential for brain development with deficiencies in specific nutrients linked to impaired cognitive function. Interventions are shown to be beneficial to children's mental development, particularly in subjects who were micronutrient-deficient at baseline but results on healthy subjects remain inconsistent. This systematic review evaluated the effect of micronutrient inventions on different cognitive domains. Studies conducted in both developing and developed countries, and trials that investigate the effect of both single and multiple micronutrient intervention were reviewed. METHODS: Systematic searches of Medline, CINAHL Plus and Academic Search database were undertaken to identify trials published after year 2000. Randomized controlled trials (RCTs) that evaluate the effect of micronutrients on cognitive performance or academic performance among children aged 4-18 years were included. RESULTS: 19 trials were identified from 18 articles. The major cognitive outcomes assessed included fluid intelligence, crystallized intelligence, short-term memory, long-term memory, cognitive processing speed, attention and concentration, and school performance. Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline. The effects of micronutrient interventions on other domains were inconsistent. CONCLUSION: Improvement in fluid intelligence among micronutrient-deficient children was consistently reported. Further research is needed to provide more definite evidence on the beneficial effects of micronutrient inventions on other cognitive domains and the effects in healthy subjects. PMID- 27395327 TI - Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety. AB - BACKGROUND: Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences. METHODS: We investigated whether developmental sex differences in cerebral blood flow mediated sex differences in anxiety and depression symptoms by capitalizing on a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin-labeled magnetic resonance imaging at 3T. Perfusion images were related to trait and state anxiety using general additive models with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty. RESULTS: Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for prescan state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in postpubertal females was mediated by elevated perfusion of the left amygdala. CONCLUSIONS: Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during adolescence may be a critical element of the affective neurobiological characteristics underlying sex differences in anxiety and mood symptoms. PMID- 27395330 TI - Effectiveness of nutritional treatment and synbiotic use on gastrointestinal symptoms reduction in HIV-infected patients: Randomized clinical trial. AB - BACKGROUND & AIMS: Gastrointestinal symptoms are among the most frequent reported complaints by people living with HIV and AIDS (PLWHA). Treatments that aim to attenuate these symptoms are important to avoid low adherence to antiretroviral therapy and to improve the quality of life. This study aimed to evaluate the effectiveness of nutritional treatment and synbiotic use in PLWHA on reducing gastrointestinal symptoms. METHODS: A randomized clinical trial nested to an outpatient cohort was conducted to evaluate the effectiveness of two treatments for gastrointestinal symptoms reduction in adult patients with antiretroviral therapy presenting at least one gastrointestinal symptom: 1) nutritional treatment + placebo (6 g maltodextrin) and 2) nutritional treatment + synbiotic (Lactobacillus and Bifidobacterium strains + 6 g fructooligosaccharides). Placebo and synbiotic were consumed twice a day during six months. The primary outcome variable was percentage reduction in the incidence of diarrhea, and secondary outcomes the decrease in the incidence of nausea and/or vomiting, dyspepsia, heartburn, constipation, flatulence, and the presence of three or more gastrointestinal symptoms. RESULTS: Out of 283 patients evaluated for eligibility, 64 met inclusion criteria to enter in this study with 1:1 allocation ratio. Both analyzed groups were homogeneous regarding sociodemographic, clinical and lifestyle variables at baseline. In the intergroup analysis, no difference was found between groups except for heartburn, which had a higher reduction in the placebo group (0.01). Regarding the intragroup analysis, in the placebo group a significant decrease in diarrhea (p = 0.02) and heartburn (p < 0.01) were observed while there was a significant reduction for nausea e/or vomit (p = 0.01), dyspepsia (p = 0.10), diarrhea (p = 0.01) and constipation (p = 0.08) in the synbiotic group. CONCLUSIONS: Diarrhea decreased in both groups, but no statistical difference between treatments was observed. The use of synbiotic appeared to reduce a greater number of symptoms although there were no statistical differences in the intergroup analysis. This clinical trial was registered at ClinicalTrials.gov (NCT02180035). PMID- 27395331 TI - Letter to the Editor of Public Health in response to Lim et al., Influenza A(H1N1)pdm09 infection in pregnant and non-pregnant women. PMID- 27395332 TI - Extreme water conservation in Alaska: limitations in access to water and consequences to health. PMID- 27395334 TI - Maternal exposure to extremely low frequency magnetic fields: Association with time to pregnancy and foetal growth. AB - BACKGROUND: Data on reproductive and developmental effects of extremely low frequency magnetic fields (ELF MFs) are inconclusive. This study tested the hypothesis that maternal exposure to ELF MFs is associated with increased time to pregnancy (TTP), reduced birthweight or small for gestational age (SGA). METHODS: The study cohort consisted of 373 mothers who gave birth between 1990 and 1994 in Kuopio University Hospital, Finland. To increase prevalence of high ELF MF exposure, women living in buildings near known ELF MF sources were included. Maternal exposure to ELF MF before and during pregnancy was assessed with short term measurements in residences and questionnaires. Associations between ELF MF exposure and TTP, low birth weight and SGA were analysed by logistic regression (or linear regression for continuous variables), adjusting for factors known to be associated with the selected pregnancy outcomes, such as maternal smoking, alcohol consumption and socioeconomic status. RESULTS: The MF exposure of the mothers was slightly higher than in Finnish residences in general, but very high exposures (>0.4MUT) were rare. No consistent association of ELF MF with TTP, birth weight or SGA was found. CONCLUSIONS: ELF MF exposure is not likely to be associated with TTP or prenatal growth at residential exposure levels that were observable in this study. PMID- 27395333 TI - Mechanisms linking high school graduation to health disparities in young adulthood: a longitudinal analysis of the role of health behaviours, psychosocial stressors, and health insurance. AB - OBJECTIVES: This study examined three competing mechanisms in the link between educational attainment and health among young adults: (a) a health behaviour mechanism; (b) a psychosocial stressor mechanism; and (c) a health insurance mechanism. The central research question was the pervasiveness and specificity of these mechanisms in the link between low educational attainment and health outcomes during young adulthood. STUDY DESIGN: A prospective longitudinal study was conducted with 808 men and women followed to age 33 years in the USA. METHODS: Health outcomes included major depressive disorder, obesity, chronic health conditions, and self-rated health. The focal predictor was educational attainment at age 21. The roles of the health behaviour mechanism (heavy episodic drinking, cigarette smoking, and meeting physical activity guidelines), the psychosocial stressor mechanism (stressful life events, perceived financial stress, and lack of control at work), and having health insurance (either through their employer or union or via family members) in the link between education and varying health outcomes were assessed using path analyses. RESULTS: Lack of health insurance emerged as a statistically significant explanatory factor underlying the association of education with depression and self-rated health. Health behaviours, specifically smoking and physical activity, were statistically significant intervening factors for obesity and self-rated health. CONCLUSIONS: The processes linking educational attainment to health inequalities begin unfolding during young adulthood. The salience of different mechanisms is specific to a health outcome rather than pervasive across multiple health outcomes. Public health policies with a broad spectrum of components, particularly focussing on smoking, physical activity, and lack of health insurance, are recommended to promote educational equalities in multiple health outcomes among young adults. PMID- 27395336 TI - Prenatal exposure to perfluorinated compounds affects thyroid hormone levels in newborn girls. AB - Perfluorinated compounds (PFCs) are ubiquitous in the environment and have been detected in humans and wildlife. Exposure to PFCs has decreased in the United States recently, while exposure to PFCs continues in Asian countries, which represents a public health concern. Various mechanisms by which PFCs affect fetal growth have been proposed, such as activation of peroxisome proliferators, disruption of thyroid hormones and changes in lipid metabolism. However, the overall evidence for an association with thyroid hormones is not strong. Therefore, we examined the effect of various prenatal PFCs on cord blood thyroid hormones: triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) levels, and explored the endocrine disrupting effect of these PFCs on thyroid hormone levels in children according to gender. Two hundred and seventy nine study participants were selected from among the enrolled participants in the Ewha Birth & Growth Retrospective Cohort, a retrospective birth cohort study conducted at Ewha Womans University Hospital, Seoul, Korea between 2006 and 2010. A generalized linear model was constructed to explore the association of PFCs and thyroid hormones. Further, an analysis stratified by gender was conducted. Our study shows that cord blood perfluoro n-pentanoic acid (PFPeA) was positively associated with cord blood T4 (p=0.01) level. Gender-specific analysis showed that prenatal PFCs: PFPeA and Perfluorohexane sulfonic acid (PFHxS) exposure significantly increased T4 (p<0.01) and T3 (p=0.03), respectively, while perfluorononanoic acid (PFNA) decreased TSH (p=0.04) concentration in newborn girls. Thus, prenatal PFC exposure may disrupt thyroid hormone homeostasis. Thyroid hormones play a crucial role in fetal development and may have gender specific action. Hence, these results are of utmost importance in high-risk groups, such as pregnant women and children. PMID- 27395335 TI - Urinary biomarkers of flame retardant exposure among collegiate U.S. gymnasts. AB - Flame retardants are widely used in polyurethane foam materials including gymnastics safety equipment such as pit cubes and landing mats. We previously reported elevated concentrations of flame retardants in the air and dust of a U.S. gymnastics training facility and elevated PentaBDE in the serum of collegiate gymnasts. Our objective in this pilot study was to compare urinary biomarkers of exposure to other flame retardants and additives of polyurethane foam including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (EH-TBB) in samples collected from 11 collegiate gymnasts before and after a gymnastics practice (n=53 urine samples total). We identified a 50% increase in the TPHP biomarker (p=0.03) from before to after practice, a non-significant 22% increase in the TDCIPP biomarker (p=0.14) and no change for the EH-TBB biomarker. These preliminary results indicate that the gymnastics training environment can be a source of recreational exposure to flame retardants. Such exposures are likely widespread, as we identified flame retardants in 89% of foam samples collected from gyms across the U.S. PMID- 27395337 TI - Inverse relationship between ambient temperature and admissions for diabetic ketoacidosis and hyperglycemic hyperosmolar state: A 14-year time-series analysis. AB - This study aimed to investigate the association of admissions for diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) with ambient temperature and season, respectively in patients with diabetes mellitus (DM), after excluding known co-morbidities that predispose onset of acute hyperglycemia events. This was a time series correlation analysis based on medical claims of 40,084 and 33,947 episodes of admission for DKA and HHS, respectively over a 14 year period in Taiwan. These episodes were not accompanied by co-morbidities known to trigger incidence of DKA and HHS. Monthly temperature averaged from 19 meteorological stations across Taiwan was correlated with monthly rate of admission for DKA or HHS, respectively, using the 'seasonal Autoregressive Integrated Moving Average' (seasonal ARIMA) regression method. There was an inverse relationship between ambient temperature and rates of admission for DKA (beta=-0.035, p<0.001) and HHS (beta=-0.016, p<0.001), despite a clear decline in rates of DKA/HHS admission in the second half of the study period. We also noted that winter was significantly associated with increased rates of both DKA (beta=0.364, p<0.001) and HHS (beta=0.129, p<0.05) admissions, as compared with summer. On the other hand, fall was associated with a significantly lower rate of HHS admission (beta=-0.016, p<0.05). Further stratified analyses according to sex and age yield essentially similar results. It is suggested that meteorological data can be used to raise the awareness of acute hyperglycemic complication risk for both patients with diabetes and clinicians to further avoid the occurrence of DKA and HHS. PMID- 27395338 TI - Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis. AB - The orteronel, abiraterone and galeterone, which were developed to treat castration resistant prostate cancer, inhibit 17,20 lyase activity but little is known about their effects on adrenal androgen biosynthesis. We studied the effect of several inhibitors and found that orteronel was selective towards 17,20 lyase activity than abiraterone and galeterone. Gene expression analysis showed that galeterone altered the expression of HSD3B2 but orteronel did not change the expression of HSD3B2, CYP17A1 and AKR1C3. The CYP19A1 activity was not inhibited except by compound IV which lowered activity by 23%. Surprisingly abiraterone caused complete blockade of CYP21A2 activity. Analysis of steroid metabolome by gas chromatography - mass spectrometry revealed changes in steroid levels caused by different inhibitors. We can conclude that orteronel is a highly specific inhibitor of 17,20 lyase activity. The discovery of these specific drug actions on steroidogenic enzyme activities would be valuable for understanding the regulation of androgens. PMID- 27395339 TI - Cold-inducible RNA-binding protein promotes epithelial-mesenchymal transition by activating ERK and p38 pathways. AB - Transforming growth factor-beta1 (TGF-beta1), a potent inducer of epithelial-to mesenchymal transition (EMT), upregulates the cold-inducible RNA-binding protein (CIRP). The link between CIRP and EMT, however, remains unknown. To determine the role of CIRP in EMT, we performed CIRP knockdown and overexpression experiments in in vitro TGF-beta1-induced EMT models. We found that CIRP overexpression promoted the downregulation of epithelial markers and the upregulation of mesenchymal markers after TGF-beta1 treatment for EMT induction. It also promoted cell migration and invasion, key features of EMT. In contrast, CIRP knockdown inhibited the downregulation of epithelial markers and the upregulation of mesenchymal markers after TGF-beta1 treatment for EMT induction. In addition, it also inhibited cell migration and invasion. Furthermore, we demonstrated that the RNA-recognition motif in CIRP is essential for the role of CIRP in EMT. At the downstream level, CIRP knockdown downregulated Snail, key transcriptional regulator of EMT, while CIRP overexpression upregulated it. We found out that the link between CIRP and Snail is mediated by ERK and p38 pathways. EMT is a critical component of carcinoma metastasis and invasion. As demonstrated in this study, the biological role of CIRP in EMT may explain why CIRP overexpression has been associated with a bad prognosis in cancer patients. PMID- 27395340 TI - Protective effect of recombinant soluble neprilysin against beta-amyloid induced neurotoxicity. AB - A few decades ago, researchers found emerging evidence showing that a number of sequential events lead to the pathological cascade of Alzheimer's disease (AD) which is caused by the accumulation of amyloid beta (Abeta), a physiological peptide, in the brain. Therefore, regulation of Abeta represents a crucial treatment approach for AD. Neprilysin (NEP), a membrane metallo-endopeptidase, is a rate-limiting peptidase which is known to degrade the amyloid beta peptide. This study investigated soluble NEP (sNEP) produced by recombinant mammalian cells stably transfected with a non-viral NEP expression vector to demonstrate its protective effect against Abeta peptides in neuronal cells in vitro. Stably transfected HEK 293 cells were used to purify the soluble protein. sNEP and Abeta peptide co-treated hippocampal cells had a decreased level of Abeta peptides shown by an increase in cell viability and decrease in apoptosis measured by the CCK-8 and relative caspase-3 activity ratio assays, respectively. This study shows that stably transfected mammalian cells can produce soluble NEP proteins which could be used to protect against Abeta accumulation in AD and subsequently neuronal toxicity. Additionally, approaches using protein therapy for potential targets could change the pathological cascade of Alzheimer's disease. PMID- 27395341 TI - Happy heart, smiling eyes: A systematic review of positive mood effects on broadening of visuospatial attention. AB - Positive mood contributes to mental and physical wellbeing. The broaden-and-build theory (Fredrickson, 2001) proposed that the beneficial effects of positive mood on life quality result from attentional broadening. In this article, we systematically review (following PRISMA guidelines; Moher et al., 2009), a host of studies investigating the nature and extent of attentional changes triggered by the experience of positive mood, with a focus on vision. While several studies reported a broadening of attention, others found that positive mood led to a more diffuse information processing style. Positive mood appears to lessen attention selectivity in a way that is context-specific and bound to limitations. We propose a new framework in which we postulate that positive mood impacts the balance between internally and externally directed attention, through modulations of cognitive control processes, instead of broadening attention per se. This novel model is able to accommodate discrepant findings, seeks to translate the phenomenon of the so-called broadening of attention with positive mood into functional terms, and provides plausible neurobiological mechanisms underlying this effect, suggesting a crucial role of the anterior and posterior cingulate cortex in this interaction. PMID- 27395342 TI - Social functioning in major depressive disorder. AB - Depression is associated with social risk factors, social impairments and poor social functioning. This paper gives an overview of these social aspects using the NIMH Research and Domain Criteria 'Systems for Social Processes' as a framework. In particular, it describes the bio-psycho-social interplay regarding impaired affiliation and attachment (social anhedonia, hyper-sensitivity to social rejection, competition avoidance, increased altruistic punishment), impaired social communication (impaired emotion recognition, diminished cooperativeness), impaired social perception (reduced empathy, theory-of-mind deficits) and their impact on social networks and the use of social media. It describes these dysfunctional social processes at the behavioural, neuroanatomical, neurochemical and genetic levels, and with respect to animal models of social stress. We discuss the diagnostic specificity of these social deficit constructs for depression and in relation to depression severity. Since social factors are importantly involved in the pathogenesis and the consequences of depression, such research will likely contribute to better diagnostic assessments and concepts, treatments and preventative strategies both at the diagnostic and transdiagnostic level. PMID- 27395343 TI - First case report of invasive pseudoterranoviasis in Italy. AB - Members of the genera Anisakis and Pseudoterranova are the main causative agents of human anisakidosis: the disease is worldwide distributed, with major impact in countries with a large consumption of raw fish. Because of unspecific symptoms and limited diagnostic tools, incidence and burden of disease are probably underestimated. In Italy, all human infestations where the etiological agent has been properly identified, have been associated to the parasitic species Anisakis pegreffii, the most frequent anisakid in the Mediterranean area. Here, an invasive human case of pseudoterranoviasis is described for the first time in Italy: in 2015, a woman was found infected during a colonoscopy scheduled after the occurrence of nonspecific clinical symptoms. The nematode was found penetrating the ascending colon. The identification was performed by sequencing the mitochondrial region cox2 and by comparison to GenBank retrieved material using the BLAST search tool. The sample showed a 99% identity with Pseudoterranova decipiens sensu stricto. The record underlines the potential risk due to the consumption of raw or undercooked imported fishes. PMID- 27395344 TI - Putting Together the Pieces of the Natriuretic Peptide Puzzle. PMID- 27395345 TI - Intrarenal Venous Flow: A Window Into the Congestive Kidney Failure Phenotype of Heart Failure? PMID- 27395346 TI - Racial and Ethnic Differences in Heart Failure Readmissions and Mortality in a Large Municipal Healthcare System. AB - OBJECTIVES: This study sought to determine whether racial and ethnic differences exist among patients with similar access to care. We examined outcomes after heart failure hospitalization within a large municipal health system. BACKGROUND: Racial and ethnic disparities in heart failure outcomes are present in administrative data, and one explanation is differential access to care. METHODS: We performed a retrospective cohort study of 8,532 hospitalizations of adults with heart failure at 11 hospitals in New York City from 2007 to 2010. Primary exposure was ethnicity and race, and outcomes were 30- and 90-day readmission and 30-day and 1-year mortality rates. Generalized estimating equations were used to test for associations between ethnicity and race and outcomes with covariate adjustment. RESULTS: Of the number of hospitalizations included, 4,305 (51%) were for blacks, 2,449 (29%) were for Hispanics, 1,494 (18%) were for whites, and 284 (3%) were for Asians. Compared to whites, blacks and Asians had lower 1-year mortality, with adjusted odds ratios (aORs) of 0.75 (95% confidence interval [CI]: 0.59 to 0.94) and 0.57 (95% CI: 0.38 to 0.85), respectively, and rates for Hispanics were not significantly different (aOR: 0.81; 95% CI: 0.64 to 1.03). Hispanics had higher odds of readmission than whites (aOR: 1.27; 95% CI: 1.03 to 1.57) at 30 (aOR: 1.40; 95% CI: 1.15 to 1.70) and 90 days. Blacks had higher odds of readmission than whites at 90 days (aOR:1.21; 95% CI: 1.01 to 1.47). CONCLUSIONS: Racial and ethnic differences in outcomes after heart failure hospitalization were present within a large municipal health system. Access to a municipal health system may not be sufficient to eliminate disparities in heart failure outcomes. PMID- 27395347 TI - Implantable Cardioverter-Defibrillator Use in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: This study evaluated the impact of implantable cardioverter defibrillators (ICDs) on mortality in patients with left ventricular assist devices (LVADs) by conducting a systematic review and meta-analysis of published studies. BACKGROUND: The burden of ventricular arrhythmias in patients with LVADs is high. Prior studies assessing the impact of ICD on survival of patients with LVADs have yielded conflicting results. METHODS: Relevant studies from January 2000 through October 2015 were identified in the databases PubMed and OVID. Weighted relative risks were estimated using random effects meta-analysis techniques. RESULTS: Six observational studies (n = 937) were included. Patients were 53 +/- 12 years of age, and 80% were male. Bridge-to-transplantation was the indication for LVAD use in 93% of the patients. A continuous-flow (CF) LVAD was present in 39% of patients. Mean left ventricular ejection fraction was 16 +/- 6%. An ICD was present in 355 patients (38%). During a mean follow-up of 7 months, 241 patients (26%) died (16% in the ICD group vs. 32% in the no-ICD group). Presence of an ICD was associated with a 39% relative risk reduction in all-cause mortality (RR: 0.61; 95% confidence interval [CI]: 0.46 to 0.82; p < 0.01). Among subgroup of patients with CF-LVAD (n = 361), ICD use was associated with a statistically nonsignificant trend toward improved survival (RR: 0.76; 95% CI: 0.51 to 1.12; p = 0.17). CONCLUSIONS: ICD use was associated with a significant reduction in mortality in LVAD patients, however, this effect was not significant in patients with CF-LVADs. Although these data support the use of ICDs, larger randomized trial data are strongly warranted to evaluate ICD effectiveness in patients with current generation LVADs. PMID- 27395348 TI - Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION. AB - OBJECTIVES: The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response. BACKGROUND: Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF). METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction <=35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity (peak oxygen consumption and 6-min walk distance) from baseline to 3 months. We also assessed for a treatment interaction among atorvastatin, simvastatin, and pravastatin and change in these endpoints with ET. Multiple linear regression analyses were performed for each endpoint, adjusting for baseline covariates. RESULTS: Of 2,331 patients in the HF-ACTION trial, 1,353 (58%) were prescribed statins at baseline. Patients treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers. There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity, nor was there evidence of differential association between statin type and ET response for these endpoints (all p values >0.05). CONCLUSIONS: In a large chronic HF cohort, there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET. These findings contrast with recent reports of an attenuation in ET response with statins in a different population, highlighting the need for future prospective studies. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437). PMID- 27395349 TI - Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM HF Trial. AB - OBJECTIVES: This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability. BACKGROUND: Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation. METHODS: Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]). RESULTS: Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality. CONCLUSIONS: Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255). PMID- 27395350 TI - Prevalence, Neurohormonal Correlates, and Prognosis of Heart Failure Stages in the Community. AB - OBJECTIVES: The purpose of this study was to describe the prevalence and prognosis of HF stages in the community; to evaluate if preclinical HF stages are characterized by elevation of pro-inflammatory (C-reactive protein), neurohormonal activation (B-type natriuretic peptide, renin and aldosterone), and cardiac stress biomarkers (high-sensitivity troponin I, ST-2, and growth differentiation factor-15). BACKGROUND: The American Heart Association/American College of Cardiology heart failure (HF) classification has 3 stages. Knowledge regarding the community burden of HF stages is limited, and data on the biomarker profile associated with HF stages are scarce, although higher concentrations of certain biomarkers are associated with preclinical HF. METHODS: We evaluated 6,770 participants (mean age 51 years; 54% women) from the Framingham Study, defining 4 stages: 1) healthy: no risk factors; 2) stage A: presence of HF risk factors (hypertension, diabetes, obesity, coronary artery disease), no cardiac structural/functional abnormality; 3) stage B: presence of prior myocardial infarction, valvular disease, left ventricular (LV) systolic dysfunction, LV hypertrophy, regional wall motion abnormality, or LV enlargement; 4) stage C/D: prevalent HF. RESULTS: The prevalence of HF stages A and B were 36.5% and 24.2%, respectively, rising with age (odds ratio: 1.70 [95% confidence interval: 1.64 to 1.77] per decade increment). In age- and sex-adjusted models, we observed a gradient of increasing biomarker levels across HF stages (p < 0.05; n = 3,416). Adjusting for age and sex, mortality rose across HF stages (232 deaths, mean follow-up 7 years), with 2- and 8-fold mortality risks for stages B and C/D, respectively, compared with healthy. CONCLUSIONS: Approximately 60% of our sample has preclinical HF, and those in stage B had higher concentrations of HF biomarkers and experienced a substantial mortality risk. PMID- 27395351 TI - Patient-Reported Outcomes in Chronic Heart Failure: Applicability for Regulatory Approval. AB - OBJECTIVES: The study sought to review the characteristics of existing patient reported outcome (PRO) instruments used with chronic heart failure (HF) patients and evaluate their potential to support an approved U.S. Food and Drug Administration (FDA) product label claim. BACKGROUND: PROs, including symptoms and their associated functional limitations, contribute substantially to HF patient morbidity. PRO measurements capture the patient perspective and can be systematically assessed with structured questionnaires, however rigorous recommendations have been set by the FDA regarding the acceptability of PRO measures as a basis for product label claims. METHODS: Extensive searches of databases and specialty guidelines identified PRO instruments used in patients with chronic HF. Information on critical properties recommended by the FDA guidance were systematically extracted and used to evaluate the selected PRO instruments. RESULTS: Nineteen PRO instruments used with chronic HF patients were identified. The Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire were the most extensively evaluated and validated in studies of this population. However, judged by criteria listed in the FDA PRO guidance, no existing PRO measure met all of the criteria to support a product label claim in the United States. CONCLUSIONS: Currently available chronic HF PRO measures do not fulfill all the recommendations provided in the FDA PRO guidance and therefore may not support an FDA-approved product label claim. Future investigations are merited to develop a PRO measure for use in patients with chronic HF in accordance with the FDA guidance. PMID- 27395352 TI - Cheating Death With ECMO: Coming Soon to a Theater Near You. PMID- 27395353 TI - Targeting N-Terminal Pro-Brain Natriuretic Peptide in Older Versus Younger Acute Decompensated Heart Failure Patients. AB - OBJECTIVES: The aim of this study was to analyze the prognostic value and attainability of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in young and elderly acute decompensated heart failure (ADHF) patients. BACKGROUND: Less-effective NT-proBNP-guided therapy in chronic heart failure (HF) has been reported in elderly patients. Whether this can be attributed to differences in prognostic value of NT-proBNP or to differences in attaining a prognostic value is unclear. The authors studied this question in ADHF patients. METHODS: Our study population comprised 7 ADHF cohorts. We defined absolute (<1,500 ng/l, <3,000 ng/l, <5,000 ng/l, and <15,000 ng/l) and relative NT-proBNP discharge cut off levels (>30%, >50%, and >70%). Six-month all-cause mortality after discharge was studied for each level in Cox regression analyses, and compared between elderly (age >75 years) and young patients (age <=75 years). Thereafter, we compared percentages of elderly and young patients attaining NT-proBNP levels (= attainability). RESULTS: A total of 1,235 patients (59% male, 45% >75 years of age) was studied. Admission levels of NT-proBNP were significantly higher in elderly versus younger patients. The prognostic value of absolute and relative NT proBNP levels was similar in elderly and young patients. Attainability was significantly lower in elderly patients for all absolute levels and a >50% relative reduction, but not for >30% and >70%. For absolute levels, attainability differences between age groups were decreased to a large extent after correction for admission NT-proBNP and anemia at discharge. For relative levels, attainability differences disappeared after correction for HF etiology and anemia at discharge. CONCLUSIONS: In young and elderly ADHF patients, it is not the prognostic value of absolute and relative NT-proBNP levels that is different, but the attainability of these levels that is lower in the elderly. This can largely be attributed to factors other than age. PMID- 27395354 TI - Two Niches in the Bone Marrow: A Hypothesis on Life-long T Cell Memory. AB - The concept is emerging that the bone marrow (BM) sustains life-long persistence of memory T cells, as it does for plasma cells. Recent studies revived the debate on how this is achieved: is the BM essentially a nest for the proliferation of recirculating memory T cells, or a storage depot for resting memory T cells? Learning from division of labor in hematopoietic stem cells, this article proposes that two distinct BM niches support memory T cell cycling and quiescence, thereby enabling memory T cells to maintain all their distinguishing features. This framework might be instrumental to interpret some puzzling findings and conceptualize the mechanisms preserving either stability of memory T cell numbers or the capacity to mount secondary responses. PMID- 27395355 TI - Polyurethane-based cell-free scaffold for the treatment of painful partial meniscus loss. AB - PURPOSE: The aim of this study was to document, at mid-term follow-up, the clinical and MRI outcome of a polyurethane-based cell-free scaffold implanted to treat painful partial meniscus loss. METHODS: Eighteen consecutive patients were enrolled and treated with arthroscopic polyurethane meniscal scaffold implantation and, in case of other comorbidities, with concurrent surgical procedures: 16 patients (9 men and 7 women, mean age 45 +/- 13 years, mean BMI 25 +/- 3, 12 medial and 4 lateral implants) were prospectively evaluated with the subjective and objective IKDC and the Tegner scores at 24, 36, 48, 60, and 72 months of follow-up. Eleven patients were also evaluated by 1.5-T MRI at the final follow-up. RESULTS: The IKDC subjective score showed a significant improvement from baseline to 24 months (45.6 +/- 17.5 and 75.3 +/- 14.8, respectively; p = 0.02) and subsequent stable results over time for up to 72 months (final score 75.0 +/- 16.8). The Tegner score improvement between pre operative status and final follow-up was also significant (p = 0.039). Nevertheless, the final score remained significantly lower than the pre-injury sports activity level (p = 0.027). High-resolution MRIs documented the presence of abnormal findings in terms of morphology, signal intensity, and interface between the implant and the native meniscus. Implant extrusion and bone oedema at the treated compartment were also observed in most of the cases, even though no correlation was found between imaging findings and clinical outcome. CONCLUSIONS: The present study reports satisfactory clinical outcomes at mid-term follow-up after polyurethane-based meniscal cell-free scaffold implantation. The treatment was effective both in cases of isolated partial meniscal lesions and in complex cases requiring the combination with other surgical procedures. On the other hand, a high rate of altered MRI aspects was documented. However, no correlation was found between the altered imaging parameters and the overall positive clinical findings, thus supporting the use of this procedure to treat painful partial meniscus loss. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 27395356 TI - Morphological classification of the femoral trochlear groove based on a quantitative measurement of computed tomographic models. AB - PURPOSE: This study aimed to investigate the natural morphology of the femoral trochlear groove based on quantitative measurement. METHODS: Computed tomographic femur models of 50 male and 50 female healthy Chinese adults (30-60 years) were analysed using three-dimensional software. Coaxial cutting planes (15 degrees increments) rotating about the trochlear groove axis from the proximal to distal point were created, followed by the deepest point of the trochlear groove marked at each cross section. The shape, position, and orientation of the trochlear groove were analysed. RESULTS: The trochlear groove was located laterally relative to the mechanical axis and consisted of the laterally oriented proximal part and medially oriented distal part. Based on the turning points located on different cross sections, the trochlear groove was classified into four types: types 45 degrees , 60 degrees , 75 degrees , and 90 degrees . The mediolateral position relative to the mechanical axis was types 45 degrees , 60 degrees , 75 degrees , and 90 degrees , from the lateral to medial side, while the distal parts of them extended along the same path. The orientation of the trochlear groove was relatively consistent and smooth, which oriented at approximately 1 degrees medially between two adjacent segments, except at approximately 10 degrees medially at the turning point. CONCLUSION: The trochlear groove tracking varies greatly amongst a population that is mainly categorized into four types. This study may be helpful for better understanding of the natural trochlear groove anatomy, prosthetic design modification, and provide the reference value for studying patellofemoral diseases such as patellar maltracking and trochlear dysplasia. LEVEL OF EVIDENCE: Prospective study, Level II. PMID- 27395357 TI - On the possibility of ephedrine detection: time-resolved fluorescence resonance energy transfer (FRET)-based approach. AB - Ephedrine is one of the main precursor compounds used in the illegal production of amphetamines and related drugs. Actually, conventional analytical methods such as high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and gas chromatography-mass spectrometry (GC-MS) are used for the detection of ephedrine; sadly, these methods require qualified personnel and are time consuming and expensive. In order to overcome these problems, in recent years, different methods have been developed based on the surface plasmon resonance (SPR) and electrochemical method. In this work, we present a simple, rapid, and effective method to detect the presence of ephedrine in solution, based on competitive fluorescence resonance energy transfer (FRET) assay. The antibody anti-ephedrine and ephedrine derivative were produced and labeled respectively, with two different fluorescent probes (donor and acceptor). The change in FRET signal intensity between donor and acceptor ephedrine compounds gives the possibility of detecting ephedrine traces of at least 0.81 +/- 0.04 ppm (LOD). Graphical abstract A new Time-resolved Fluorescence Resonance Energy Transfer (FRET) assay for ephedrine detection. PMID- 27395358 TI - Assessing heavy metal sources in sugarcane Brazilian soils: an approach using multivariate analysis. AB - Brazil is the world's largest sugarcane producer and soils in the northeastern part of the country have been cultivated with the crop for over 450 years. However, so far, there has been no study on the status of heavy metal accumulation in these long-history cultivated soils. To fill the gap, we collect soil samples from 60 sugarcane fields in order to determine the contents of Cd, Cr, Cu, Ni, Pb, and Zn. We used multivariate analysis to distinguish between natural and anthropogenic sources of these metals in soils. Analytical determinations were performed in ICP-OES after microwave acid solution digestion. Mean concentrations of Cd, Cr, Cu, Ni, Pb, and Zn were 1.9, 18.8, 6.4, 4.9, 11.2, and 16.2 mg kg(-1), respectively. The principal component one was associated with lithogenic origin and comprised the metals Cr, Cu, Ni, and Zn. Cluster analysis confirmed that 68 % of the evaluated sites have soil heavy metal concentrations close to the natural background. The Cd concentration (principal component two) was clearly associated with anthropogenic sources with P fertilization being the most likely source of Cd to soils. On the other hand, the third component (Pb concentration) indicates a mixed origin for this metal (natural and anthropogenic); hence, Pb concentrations are probably related not only to the soil parent material but also to industrial emissions and urbanization in the vicinity of the agricultural areas. PMID- 27395359 TI - Water quality of the main tributaries of the Parana Basin: glyphosate and AMPA in surface water and bottom sediments. AB - The Parana River, the sixth largest in the world, is the receptor of pollution loads from tributaries traversing urban and industrialized areas plus agricultural expanses, particularly so in the river's middle and lower reaches along the Argentine sector. In the present study, we analyzed and discussed the main water quality parameters, sediment compositions, and content of the herbicide glyphosate plus its metabolite aminomethylphosphonic acid (AMPA) in water and sediments. Samples were obtained from distal positions in the principal tributaries of the Parana and the main watercourse during surveys conducted in 2011 and 2012 to monitor the basin. Only 15 % of the water samples contained detectable concentrations of glyphosate at an average concentration of 0.60 MUg/L, while no detectable levels of AMPA were observed. The herbicide and metabolite were primarily present in sediments of the middle and lower stretch's tributaries, there occurring at a respective average of 37 and 17 % in samples. The mean detectable concentrations measured were 742 and 521 MUg/kg at mean, maximum, and minimum glyphosate/AMPA ratios of 2.76, 7.80, and 0.06, respectively. The detection of both compounds was correlated with the presence of sulfides and copper in the sediment matrix. PMID- 27395360 TI - Adverse effect of agroecosystem pond water on biological endpoints of common toad (Rhinella arenarum) tadpoles. AB - Chemical prroducts used in farming and wastes from livestock can contaminate pond water in agroecosystems due to runoff. Amphibians using these ponds for breeding are probably exposed to pollutants, and serious consequences might be observed afterward at the population level. Assessment biological endpoints of anuran to water quality give a realistic estimate of the probability of occurrence of adverse effects and provide an early warning signal. In this study, the ecotoxicity of agroecosystem ponds from the south of Cordoba province, Argentina, was investigated. Ponds in four sites with different degrees of human disturbance were selected: three agroecosystems (A1, A2, A3) and a site without crops or livestock (SM). The effect of pond water quality on the biological endpoint of Rhinella arenarum tadpoles was examined using microcosms with pond water from sites. Biological endpoints assessed were as follows: mortality, growth, development, morphological abnormalities (in body shape, gut, and labial tooth row formula), behavior, and blood cell parameters (micronucleus and nuclear abnormalities). Results indicated that water from agroecosystems has adverse effect on early life stage of R. arenarum. High mortality and fewer metamorphs were recorded in the A1 and A3 treatments. Tadpoles and metamorphs from A1 and A2 treatments had lower body condition. Tadpoles from A1 and A3 showed the highest prevalence of morphological abnormalities. The lowest amount of tadpoles feeding and the highest percentage of tadpoles swimming on the surface were observed in treatments with agroecosystem pond water. The higher frequencies of micronuclei and nuclear abnormalities were recorded in tadpoles from A1, A2, and A3 treatments. We check the sensitivity of the biological endpoints of R. arenarum tadpoles like early warning indicators of water quality. We found that the poor water quality of agroecosystem ponds has impact on the health of the tadpoles, and this could affect the persistence of populations. We recommend implementation of management actions before the harmful effects of agroecosystem pond water on early life stage of anuran become evident in higher ecological levels. PMID- 27395361 TI - Heavy metal contaminations in soil-rice system: source identification in relation to a sulfur-rich coal burning power plant in Northern Guangdong Province, China. AB - Heavy metal contents (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in 99 pairs of soil rice plant samples were evaluated from the downwind directions of a large thermal power plant in Shaoguan City, Guangdong Province, China. Results indicate that there is a substantial buildup of As, Cd, Cu, Pb, and Zn in the predominant wind direction of the power plant. The significant correlations between S and heavy metals in paddy soil suggest that the power plant represents a source of topsoil heavy metals in Shaoguan City due to sulfur-rich coal burning emissions. Elevated Cd concentrations were also found in rice plant tissues. Average Cd (0.69 mg kg( 1)) and Pb (0.39 mg kg(-1)) contents in rice grain had exceeded their maximum permissible limits (both were 0.2 mg kg(-1)) in foods of China (GB2762-2005). The enrichment of Cd and Pb in rice grain might pose a potential health risk to the local residents. PMID- 27395362 TI - Hypokalemia is a biochemical signal of poor prognosis for acute paraquat poisoning within 4 hours. AB - Anecdotal reports have suggested that hypokalemia is an independent predictor of mortality in patients with acute paraquat poisoning. However, the clinical significance of hypokalemia has not been systematically investigated in the early stage of paraquat poisoning. This study aimed to evaluate whether initial hypokalemia is a good predictor of mortality in patients with acute paraquat poisoning within 4 h. We retrospectively analyzed patients who were admitted to the emergency department after paraquat poisoning between September 2012 and January 2015. Demographic, clinical, and laboratory data were recorded, and the prognostic significance of hypokalemia was analyzed. A total of 120 patients were included. The 60-day mortality was 71.7 %. Serum potassium concentrations were significantly lower in non-survivors (3.1 +/- 0.5 mmol/L) than in survivors (3.8 +/- 0.3 mmol/L, P < 0.001). Independent predictors of death were amount of paraquat ingested (hazard ratio 1.005; 95 % confidence interval 1.002-1.007), serum potassium (0.498, 0.277-0.897), bicarbonate (0.934, 0.876-0.995), and white blood cell count (1.032, 1.001-1.065). For receiver operating characteristic curve analysis, serum potassium had an area under the curve of 0.852 (95 % confidence interval 0.784-0.920, P < 0.001), and the best cutoff value was 3.5 mmol/L (sensitivity, 88.2 %; specificity, 75.6 % in predicting survivors). Kaplan Meier analysis showed that decreased serum potassium concentrations were associated with an increase in 60-day mortality (P < 0.001). Hypokalemia may be a reliable predictor in evaluating prognosis in paraquat poisoning within 4 h. The mechanism is not clear, and further studies verifying the precise mechanism of hypokalemia are required. PMID- 27395363 TI - The use of cassava leaf silage as a substitute for concentrate feed in sheep. AB - We aimed to evaluate nutrient intake, performance and rumen fermentation of sheep fed cassava leaf silage (CLS). Sixteen growing Java thin-tailed male sheep (body weight (BW) 20.4 +/- 1.9 kg) were fed one of the following dietary treatments: T0 (100 % forage); T1 (100 % chopped forage); T2 (80 % chopped forage + 20 % concentrate); and T3 (80 % chopped forage + 20 % CLS). Nutrient intake, production performance and rumen fermentation characteristics were measured. There was no significant effect on the consumption of dry matter, whereas there was a significant effect (P < 0.05) on the consumption of crude protein, fat, crude fibre and total digestible nutrients. Concentrate or CLS at a 20 % level could increase BW and feed efficiency. No significant difference was observed in total bacteria; however, concentrate could increase total protozoa (P < 0.05). Total volatile fatty acids were higher in T2 than in T3, but ammonia concentration was higher in T3 than in T2. In conclusion, feeding 20 % cassava leaf silage greatly improved sheep performance, approaching that achieved by feeding concentrate. PMID- 27395364 TI - QRS interval: What is it? How to measure it? PMID- 27395365 TI - Comparison of the spatial QRS-T angle derived from digital ECGs recorded using conventional electrode placement with that derived from Mason-Likar electrode position. AB - BACKGROUND: The spatial QRS-T angle is ideally derived from orthogonal leads. We compared the spatial QRS-T angle derived from orthogonal leads reconstructed from digital 12-lead ECGs and from digital Holter ECGs recorded with the Mason-Likar (M-L) electrode positions. METHODS AND RESULTS: Orthogonal leads were constructed by the inverse Dower method and used to calculate spatial QRS-T angle by (1) a vector method and (2) a net amplitude method, in 100 volunteers. Spatial QRS-T angles from standard and M-L ECGs differed significantly (57 degrees +/-18 degrees vs 48 degrees +/-20 degrees respectively using net amplitude method and 53 degrees +/-28 degrees vs 48 degrees +/-23 degrees respectively by vector method; p<0.001). Difference in amplitudes in leads V4-V6 was also observed between Holter and standard ECGs, probably due to a difference in electrical potential at the central terminal. CONCLUSION: Mean spatial QRS-T angles derived from standard and M-L lead systems differed by 5 degrees -9 degrees . Though statistically significant, these differences may not be clinically significant. PMID- 27395366 TI - Pseudolipoblastic perineurioma: an unusual morphological variant of perineurioma that may simulate liposarcoma. AB - Perineuriomas are rare peripheral nerve sheath tumors arising from or differentiating along the lines of normal perineurial cells. They can be divided into intraneural and soft tissue types, with the latter category including a significant number of morphological variants. Herein, we further expand their morphological spectrum to include "pseudolipoblastic" perineuriomas. These lesions occurred in the tongue of a 30-year-old man and in the triceps of a 67 year-old woman and were characterized by bland, epithelioid cells with striking intracytoplasmic vacuolization. The architecture varied, with some areas showing a striking "net-like" or "microreticular" pattern and smaller areas having a more typical spindled and whorled appearance. Clinical follow-up (5months and 52months, respectively) showed no evidence of local recurrence or metastasis. Multiple perineurial markers, including epithelial membrane antigen, claudin-1, GLUT-1, and collagen IV, were diffusely positive. Both cases were submitted in consultation out of concern that they represented high-grade liposarcomas. To the best of our knowledge, this unusual morphological variant of perineurioma has not been reported. These tumors appear to be entirely benign and should be cured with simple excision. Pseudolipoblastic perineuriomas should be distinguished from round cell and epithelioid pleomorphic liposarcomas, as well as from other tumors that may show prominent intracytoplasmic vacuolization. PMID- 27395367 TI - Dentin-composite bond strength measurement using the Brazilian disk test. AB - OBJECTIVES: This study presents a variant of the Brazilian disk test (BDT) for assessing the bond strength between composite resins and dentin. METHODS: Dentin composite disks (phi 5mm*2mm) were prepared using either Z100 or Z250 (3M ESPE) in combination with one of three adhesives, Adper Easy Bond (EB), Adper Scotchbond Multi-Purpose (MP) and Adper Single Bond (SB), and tested under diametral compression. Acoustic emission (AE) and digital image correlation (DIC) were used to monitor debonding of the composite from the dentin ring. A finite element (FE) model was created to calculate the bond strengths using the failure loads. Fracture modes were examined by scanning electron microscopy (SEM). RESULTS: Most specimens fractured along the dentin-resin composite interface. DIC and AE confirmed interfacial debonding immediately before fracture of the dentin ring. Results showed that the mean bond strength with EB (14.9+/-1.9MPa) was significantly higher than with MP (13.2+/-2.4MPa) or SB (12.9+/-3.0MPa) (p<0.05); no significant difference was found between MP and SB (p>0.05). Z100 (14.5+/ 2.3MPa) showed higher bond strength than Z250 (12.7+/-2.5MPa) (p<0.05). Majority of specimens (91.3%) showed an adhesive failure mode. EB failed mostly at the dentin-adhesive interface, whereas MP at the composite-adhesive interface; specimens with SB failed at the composite-adhesive interface and cohesively in the adhesive. CONCLUSIONS: The BDT variant showed to be a suitable alternative for measuring the bond strength between dentin and composite, with zero premature failure, reduced variability in the measurements, and consistent failure at the dentin-composite interface. CLINICAL SIGNIFICANCE: The new test could help to predict the clinical performance of adhesive systems more effectively and consistently by reducing the coefficient of variation in the measured bond strength. PMID- 27395368 TI - Evaluation of current feeding practices in the critically ill: A retrospective chart review. AB - BACKGROUND: Worldwide, malnutrition is an important issue in the care of the critically ill which is associated with increased costs of care and poor patient outcomes. OBJECTIVES: To evaluate the current state of enteral nutrition in the critically ill in the U.S. in comparison to international practices. RESEARCH METHODOLOGY/DESIGN: A retrospective chart audit was performed utilising a 10% random sample of patients admitted to the Pulmonary Medicine Service at an academic medical center in the U.S. from 1/1/11 to 12/31/11. A total of 69 charts were audited. OUTCOME MEASURES: Outcome measures included time to initiation of feeds, prescribed versus received protein and energy on day three, prokinetic use and markers of nutritional status. RESULTS: Delayed time to feeding, greater than 48hours after ICU admission, was present in 66.7% of the sample. On day three only 9% of the sample was receiving 80% or more of the prescribed protein or energy. These findings are similar to those found internationally. CONCLUSION: Critically ill patients continue to experience delays in enteral feeding initiation and are frequently not meeting nutrition targets. Interventions aimed at improving nutrition delivery in the intensive care unit should be a focus of quality care both in the U.S. and internationally. PMID- 27395369 TI - Biodistribution and toxicity evaluation of sesbania mosaic virus nanoparticles in mice. AB - Sesbania mosaic virus (SeMV), a 30-nm spherical plant sobemovirus, is suitable for developing functionalized nanoparticles for biomedical applications. However, the in vivo behavior of SeMV and the clinical impact following its delivery via the oral or intravenous route are not known. To address this question, we examined the biodistribution, toxicity and histopathological changes in SeMV treated mice. No toxic effects were observed in mice administered high doses (100 mg and 200 mg per kg body weight orally or 40 mg and 80 mg per kg body weight intravenously) of SeMV, and they were found to be normal. Analysis of fecal sample showed that SeMV was cleared in 16 h when 20 mg of the virus per kg body weight was administered orally. RT-PCR analysis of blood samples showed that SeMV was present up to 72 h in mice inoculated either intravenously (8 mg/kg body weight) or orally (20 mg/kg body weight). Further, SeMV was found to be localized up to 72 h in spleen and liver tissues of intravenously inoculated mice only. Biochemical and hematological parameters were found to be normal at 6 and 72 h after administration of SeMV. Furthermore, no noticeable changes were observed in histological sections of brain, liver, spleen, lungs and kidney tissue samples collected at 6 and 72 h from SeMV administered mice when compared to control mice. Thus, SeMV appears to be a safe and non-toxic platform that can be tailored as a nanocarrier for in vivo biomedical applications. PMID- 27395370 TI - Comparison between passive vision-based system and a wearable inertial-based system for estimating temporal gait parameters related to the GAITRite electronic walkway. AB - Quantitative gait analysis allows clinicians to assess the inherent gait variability over time which is a functional marker to aid in the diagnosis of disabilities or diseases such as frailty, the onset of cognitive decline and neurodegenerative diseases, among others. However, despite the accuracy achieved by the current specialized systems there are constraints that limit quantitative gait analysis, for instance, the cost of the equipment, the limited access for many people and the lack of solutions to consistently monitor gait on a continuous basis. In this paper, two low-cost systems for quantitative gait analysis are presented, a wearable inertial system that relies on two wireless acceleration sensors mounted on the ankles; and a passive vision-based system that externally estimates the measurements through a structured light sensor and 3D point-cloud processing. Both systems are compared with a reference clinical instrument using an experimental protocol focused on the feasibility of estimating temporal gait parameters over two groups of healthy adults (five elders and five young subjects) under controlled conditions. The error of each system regarding the ground truth is computed. Inter-group and intra-group analyses are also conducted to transversely compare the performance between both technologies, and of these technologies with respect to the reference system. The comparison under controlled conditions is required as a previous stage towards the adaptation of both solutions to be incorporated into Ambient Assisted Living environments and to provide continuous in-home gait monitoring as part of the future work. PMID- 27395371 TI - Translation of Contextual Control Model to chronic disease management: A paradigm to guide design of cognitive support systems. AB - BACKGROUND: Electronic health records (EHRs) continue to be criticized for providing poor cognitive support. Defining cognitive support has lacked theoretical foundation. We developed a measurement model of cognitive support based on the Contextual Control Model (COCOM), which describes control characteristics of an "orderly" joint system and proposes 4 levels of control: scrambled, opportunistic, tactical, and strategic. METHODS: 35 clinicians (5 centers) were interviewed pre and post outpatient clinical visits and audiotaped during the visit. Behaviors pertaining to hypertension management were systematically mapped to the COCOM control characteristics of: (1) time horizon, (2) uncertainty assessment, (3) consideration of multiple goals, (4) causal model described, and (5) explicitness of plan. Each encounter was classified for overall mode of control. Visits with deviation versus no deviation from hypertension goals were compared. RESULTS: Reviewer agreement was high. Control characteristics differed significantly between deviation groups (Wilcox rank sum p<.01). K-means cluster analysis of control characteristics, stratified by deviation were distinct, with higher goal deviations associated with more control characteristics. CONCLUSION: The COCOM control characteristics appear to be areas of potential yield for improved user-experience design. PMID- 27395372 TI - Using machine learning methods for predicting inhospital mortality in patients undergoing open repair of abdominal aortic aneurysm. AB - An abdominal aortic aneurysm is an abnormal dilatation of the aortic vessel at abdominal level. This disease presents high rate of mortality and complications causing a decrease in the quality of life and increasing the cost of treatment. To estimate the mortality risk of patients undergoing surgery is complex due to the variables associated. The use of clinical decision support systems based on machine learning could help medical staff to improve the results of surgery and get a better understanding of the disease. In this work, the authors present a predictive system of inhospital mortality in patients who were undergoing to open repair of abdominal aortic aneurysm. Different methods as multilayer perceptron, radial basis function and Bayesian networks are used. Results are measured in terms of accuracy, sensitivity and specificity of the classifiers, achieving an accuracy higher than 95%. The developing of a system based on the algorithms tested can be useful for medical staff in order to make a better planning of care and reducing undesirable surgery results and the cost of the post-surgical treatments. PMID- 27395373 TI - Polymorphic Variants 279R and 668Q Augment Activity of Matrix Metalloproteinase-9 in Breath Condensates of Children with Asthma. AB - Matrix metalloproteinase (MMP)-9 is involved in pathophysiology of asthma, mainly asthma-associated airway remodeling. Exhaled breath condensates (EBC) of asthmatics contain increased amounts of MMP-9 with activity higher, than in healthy controls. The increased activity of MMP-9 may originate from its excessive production and activation, but may also result from variations in MMP-9 structure, which are determined by single nucleotide polymorphisms (SNPs). In this pilot study we aimed to assess the possible influence of two functional MMP 9 polymorphisms, Q279R and R668Q, on enzymatic activity of MMP-9, measured in EBC of asthmatic children. The concentration and activity of MMP-9 were analyzed in EBC of 20 children with allergic asthma using specific standard ELISA and novel immunoenzymatic activity assay. The SNPs of MMP-9 were assessed using real-time PCR-based genotyping test. We have found that MMP-9 concentration in breath condensates of children with stable asthma was slightly higher in ELISA, than in the activity assay. Moreover, these results and activity-to-amount ratio have revealed some relationship with a presence of specific 279R and/or 668Q MMP-9 gene variants. Our observation suggests that at least in some patients MMP-9 hyperactivity may result from genetic predisposition, determined by polymorphic variants of MMP-9 gene. Moreover, it supports previous reports postulating significance of MMP-9 in pathogenesis of asthma. However, this issue still requires further studies. PMID- 27395375 TI - The evaluation of perceived stress and associated factors in elderly caregivers. AB - OBJECTIVE: Factors associated with perceived stress in older people have been studied previously, but this investigation in elderly caregivers is still scarce in the literature. Our aim was to assess factors that are associated with perceived stress in a sample of elderly caregivers. METHODS: This cross-sectional investigation assessed 341 elderly caregivers who cared for a dependent older person at home. They answered questionnaires including the Perceived Stress Scale (PSS-14), a sociodemographic and care characterization, health and cognitive status, and burden related to care. RESULTS: The mean score in PSS-14 was 18.5+/ 9.9. Self-reported pain, difficult to sleep, "very poor/poor" self-rated health, impaired cognitive status, more people living in the house and higher levels of burden related to care were associated with higher levels of perceived stress. DISCUSSION: The results highlight the importance of the development of stress reduced interventions directed to elderly caregivers focusing on the associated variables in this study. Attention should be given to cognitive decline prevention and strategies to avoid or reduce burden in the elderly caregivers. PMID- 27395374 TI - Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients. AB - PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85alpha, p110gamma, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85alpha 43/66 (65 %), p110gamma41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed. PMID- 27395376 TI - Are health assets associated with improved outcomes for hospitalised older adults? A systematic review. AB - OBJECTIVE: Health assets are protective factors that support health and wellbeing, rather than risk factors that are associated with disease. This concept was developed in the community setting. In hospitalised older adults, the dominant approach has been to identify risk factors, with little examination of health assets. The purpose of this systematic review was to determine whether, in hospitalised older people, individual health assets decrease the risk of post hospital mortality, functional decline, new need for residential care, readmission or longer length of stay. METHODS: MEDLINE, EMBASE, CINAHL and PsycINFO were searched to identify studies examining outcomes for hospitalised older adults. Included studies examined at least one potential individual health asset, which was a psychosocial characteristic or health characteristic. Study quality was assessed, and findings are narratively described. RESULTS: Nine prospective cohort and two retrospective cohort studies were identified. subjective, functional and biological health assets were identified. Health assets were associated with decreased risk of post-hospital mortality, functional decline, new need for residential care and readmission. CONCLUSION: The complex interplay between health status and psychological and social factors is incompletely understood. Health assets are associated with improved outcomes for hospitalised older adults. The small number of studies suitable for inclusion indicates the need for further research in this area. PMID- 27395377 TI - The availability and affordability of long-term care for disabled older people in China: The issues related to inequalities in social security benefits. AB - BACKGROUND: China is experiencing increasing pressure from issues relating to an ageing population. The rationality of different eligibility criteria of the benefits within the social security system has been widely challenged; however, to date, no previous study has explored its association with the availability and affordability of long-term care (LTC). AIM: This study evaluates the availability and affordability of Long-Term Care (LTC) services for disabled older people (aged 65 and above) in China, with special attention to the differences among groups in receipt of specific social security benefits. METHODS: The data of availability and affordability of LTC services for disabled older people is from a nationally representative sample Chinese Longitudinal Healthy Longevity Survey (CLHLS). Three different social security benefits were identified and their effects on the long-term care services for disabled older people were explored. RESULTS: The overall proportions of disabled older people who have only limited or no available or affordable LTC services were remarkably high, especially for those who have moderate or no social security benefits. Compared to those who are entitled to generous social security benefits, older people who have no social security benefits are 18.45 times more likely to be unable to afford health care expenses. CONCLUSION: The findings imply that policy makers in China could focus on the LTC needs for the social security and socioeconomically disadvantaged (who have limited or no social security benefits and in low household income) disabled older people which could reduce the gap between them and those who are entitled to generous social security benefits. PMID- 27395378 TI - High-resolution radiation mapping to investigate FDNPP derived contaminant migration. AB - As of March 2016, five years will have passed since the earthquake and ensuing tsunami that crippled the Fukushima Daiichi Nuclear Power Plant on Japan's eastern coast, resulting in the explosive release of significant quantities of radioactive material. Over this period, significant time and resource has been expended on both the study of the contamination as well as its remediation from the affected environments. Presented in this work is a high-spatial resolution foot-based radiation mapping study using gamma-spectrometry at a site in the contaminated Iitate Village; conducted at different times, seventeen months apart. The specific site selected for this work was one in which consistent uniform agriculture was observed across its entire extent. From these surveys, obtained from along the main northwest trending line of the fallout plume, it was possible to determine the rate of reduction in the levels of contamination around the site attributable to the natural decay of the radiocesium, remediation efforts or material transport. Results from the work suggest that neither the natural decay of radiocesium nor its downward migration through the soil horizons were responsible for the decline in measured activity levels across the site, with the mobilisation of contaminant species likely adhered to soil particulate and the subsequent fluvial transport responsible for the measurable reduction in activity. This transport of contaminant via fluvial methods has already well studied implications for the input of contaminant material entering the neighbouring Pacific Ocean, as well as the deposition of material along rivers within previously decontaminated areas. PMID- 27395379 TI - Evidence of Local HIV Transmission in the African Community of King County, Washington. AB - Little is known about the frequency of ongoing HIV transmission within U.S. African immigrant communities. We used HIV surveillance and partner services data to describe African-born persons newly reported with HIV infection in King County (KC), WA from 1/1/2010 to 12/31/2013. We performed phylogenetic clustering analysis of HIV-1 pol to identify putative transmission events within this population. From 2010 to 2013, 1148 KC adults were reported with HIV, including 102 (9 %) born in Africa. Forty-one African-born cases were interviewed and reported diagnosis after arrival in the U.S. Fourteen (34 %) reported >=1 negative test prior to diagnosis, and 9 (26 %) reported >=1 negative test after U.S. arrival. Pol genotypes were available for seven of these nine. For two of these seven, a KC case was the nearest phylogenetic neighbor; two others were infected with subtype B virus. We found substantial evidence of ongoing HIV transmission in the African community of KC. PMID- 27395380 TI - Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline. AB - BACKGROUND/AIMS: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates. METHODS: To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double blind, placebo-controlled studies. CF patients were treated with 25 mg amitriptyline twice daily, i.e. a total dose of 50 mg/d. After those two studies part of the patients used amitriptyline in an off-lable-use for routine treatment. These patients were observed after one, two and three years after continuous use of amitriptyline and were matched with those patients who were not treated. These patients were used as a control group. RESULTS: After one year of treatment, forced expiratory volume in 1 sec predicted (FEV1) increased significantly by 7.6+/-7.0%, p=<0.001, and weight increased by 2.1+/-2.3kg, p=<0.001 in the amitriptyline population (n=20), whereas FEV1 decreased significantly in the control group by 1.8+/-3.3%, p=0.010, and weight increased by 1.1+/-2.7kg, p=0.010 (n=14). After two years of treatment, FEV1 increased significantly by 5.6+/-10.3%, p=0.009, and weight increased by 3.6+/-2.9kg, p=<0.001 in the amitriptyline population (n=12). In contrast, FEV1 decreased in the control group by 2.1+/-3.7%, p=0.051 and weight increased by only 0.4+/ 2.9kg, p=0.31 (n=10). After three years of treatment, FEV1 increased significantly by 7.7+/-8%, p=0.050, and weight increased by 7.3+/-3.8kg, p=0.016, in the amitriptyline population (n=5), whereas FEV1 decreased in the control group by 1.0+/-1.3%, p=0.075 and weight increased by 0.4+/-1.5kg, p=0.29 (n=5). CONCLUSION: Amitriptyline significantly increases FEV1, reduces ceramide in lung cells and increases weight of CF patients. PMID- 27395381 TI - From Postpartum Haemorrhage Guideline to Local Protocol: A Study of Protocol Quality. AB - Objective Postpartum hemorrhage (PPH) has a continuously rising incidence worldwide, suggesting suboptimal care. An important step in optimizing care is the translation of evidence-based guidelines into comprehensive hospital protocols. However, knowledge about the quality of these protocols is lacking. The objective of this study was to evaluate the quality of PPH-protocols on structure and content in the Netherlands. Methods We performed an observational multicenter study. Eighteen PPH-protocols from 3 University Hospitals (UH), 8 Teaching Hospitals (TH) and 7 Non-Teaching hospitals (NTH) throughout the Netherlands were acquired. The structure of the PPH-protocols was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) Instrument. The content was appraised using previously developed quality indicators, based on international guidelines and Advance-Trauma-Life-Support (ATLS)-based course instructions. Results The quality of the protocols for postpartum hemorrhage for both structure and content varied widely between different hospitals, but all of them showed room for improvement. The protocols scored mainly below average on the different items of the AGREE-II instrument (8 of the 10 items scored <4 on a 1-7 scale). Regarding the content, adoption of guideline recommendations in protocols was 46 %. In addition, a timely indication of 'when to perform' a recommendation was lacking in three-fourths of the items. Conclusion This study shows that the quality of the PPH-protocols for both structure and content in the Netherlands is suboptimal. This makes adherence to the guideline and ATLS-based course instructions difficult. PMID- 27395382 TI - Effect of a Best Practice Alert on Gestational Weight Gain, Health Services, and Pregnancy Outcomes. AB - Objective To examine whether an electronic medical record "best practice alert" previously shown to improve antenatal gestational weight gain patient education resulted in downstream effects on service delivery or patient health outcomes. Methods This study involved secondary analysis of data from an intervention to improve provider behavior surrounding gestational weight gain patient education. Data were from retrospective chart reviews of patients who received care either before (N = 333) or after (N = 268) implementation of the intervention. Pre-post comparisons and multivariable logistic regression were used to analyze downstream effects of the intervention on health outcomes and obesity-related health services while controlling for potential confounders. Results The intervention was associated with an increase in the proportion of prenatal patients who gained weight within Institute of Medicine guidelines, from 28 to 35 % (p < .05). Mean total gestational weight gain did not change, but variability decreased such that post-intervention women had weight gains closer to their gestational weight gain targets. The intervention was associated with a 94 g decrease in mean infant birth weight (p = .03), and an increase in the proportion of overweight and obese women screened for undiagnosed Type 2 diabetes before 20 weeks gestation, from 13 to 25 % (p = .01). Conclusions for Practice The electronic medical record can be leveraged to promote healthy gestational weight gain and early screening for undiagnosed Type 2 diabetes. Yet most patients still need additional support to achieve gestational weight gain within Institute of Medicine guidelines. PMID- 27395383 TI - What do Pregnant Women Know About the Healthy Eating Guidelines for Pregnancy? A Web-Based Questionnaire. AB - Objectives This study explored nutrition knowledge of pregnant women, and how it correlated with participant characteristics, their main sources of information and changes to their diet since becoming pregnant. Methods Pregnant women residing in Australia accessing pregnancy forums on the internet were invited to complete a web-based questionnaire on general nutrition and pregnancy-specific nutrition guidelines. Results Of the 165 eligible questionnaire responses, 114 were complete and included in the analysis. Pregnancy nutrition knowledge was associated with education (r s = 0.21, p < 0.05) and income (r s = 0.21, p < 0.05). Only 2 % of pregnant women achieved nutrition knowledge scores over 80 %. Few women received nutrition advice during their pregnancy, of which most were advised by their doctor. Dietary changes adopted since becoming pregnant included consuming more fruit, vegetables, dairy and high fibre foods. Conclusions for Practice Pregnant women in this study had limited knowledge of the dietary guidelines for healthy eating during pregnancy. Furthermore, nutrition counselling in maternity care appears to be infrequent. One approach to optimising maternal diets and subsequently preventing adverse health outcomes is to enhance their knowledge of the pregnancy nutrition guidelines through the provision of nutritional counselling. Furthermore, research exploring the access and use of nutrition resources, and nutrition advice provided to pregnant women is recommended to understand how knowledge impacts on dietary behaviour. PMID- 27395384 TI - Severe Neonatal Morbidity Among Births to Refugee Women. AB - Background Despite being considered high risk, little is known about the perinatal health of refugees in developed countries. Our objectives were to examine whether: (1) the healthy migrant effect applies to infants born to refugee women with respect to severe neonatal morbidity (SNM); (2) refugee status was a risk factor for SNM among immigrants; (3) refugee sponsorship status was a risk factor for SNM by comparing asylum-seekers to sponsored refugees; and (4) refugees were at greater risk of specific SNM subtypes. Methods Immigration records (1985-2010) linked to Ontario hospital data (2002-2010) were used to examine SNM. We calculated adjusted risk ratios (ARR) with 95 % confidence intervals (95 % CI) for SNM and unadjusted risk ratios with 99 % CI for SNM subtypes using log-binomial regression. Results There were borderline differences in SNM among refugees (N = 29,755) compared to both non-immigrants (N = 860,314) (ARR = 0.94, 95 % CI 0.89, 0.99) and other immigrants (N = 230,847) (ARR = 1.10, 95 % CI 1.04, 1.18) with a larger difference comparing other immigrants to non immigrants (ARR = 0.83, 95 % CI 0.81, 0.85). Asylum-seekers did not differ from sponsored refugees (ARR = 1.07, 95 % CI 0.90, 1.27). Though rare, several SNM subtypes were significant with large effect sizes. Conclusion With respect to SNM risk, the healthy migrant effect clearly applies to non-refugee immigrants, but is weaker for refugees and may not apply. Among immigrants, refugee status was a weak risk factor for SNM and may not be clinically important. Sponsorship status was not associated with greater risk of SNM. Further investigation of several SNM subtypes is warranted. PMID- 27395385 TI - Provision of Lipid-Based Nutrient Supplements from Age 6 to 18 Months Does Not Affect Infant Development Scores in a Randomized Trial in Malawi. AB - Objectives Undernutrition during early life contributes to more than 200 million children globally not fulfilling their developmental potential. Our objective was to determine whether dietary supplementation with several formulations of lipid based nutrient supplements (LNS), which differed in dose per day and milk content, positively affect infant development in Malawi. Methods We randomly assigned 1932 infants age 6 months to receive one of the following for 12 months: 10, 20 g, or 40 g/day milk-containing LNS, 20 g or 40 g/day milk-free LNS, or no supplement until 18 months of age (control group). We assessed motor, language, socio-emotional, and executive function at age 18 months. Primary analysis was by intention-to-treat and we also examined 13 potential effect modifiers, including the child's initial nutritional status and level of developmental stimulation. The study is registered as clinical trial NCT00945698. Results We found no significant differences between intervention groups in any scores. The difference in mean z-scores between children in the control group and children in the intervention groups ranged from -0.08 to 0.04 for motor development (p = 0.76), 0.05 to 0.01 for language development (p = 0.97), -0.15 to 0.11 for socio emotional development (p = 0.22), and -0.02 to 0.20 for executive function (p = 0.24). We did not find that initial nutritional status, developmental stimulation, or other factors modified the effect LNS versus control group. Conclusions for Practice Our results suggest that in a population such as this one, provision of LNS from age 6 to 18 months would not affect motor, language, socio-emotional, or executive function skills at age 18 months. PMID- 27395386 TI - Refractory chronic migraine: is drug withdrawal necessary before starting a therapy with onabotulinum toxin type A? AB - Onabotulinum toxin A (BT-A) is now one of the authorized prophylaxis treatments for chronic migraine (CM) thanks to previous clinical trials, which usually required a pharmacologic washout as a precondition for demonstrating its efficacy. Aim of our study was to assess the efficacy in daily clinical practice of BT-A injections in refractory CM patients, regardless of medication overuse without any standardized withdrawal protocol and without stopping the ongoing prophylaxis treatment as well. We treated 44 refractory CM patients (37 females and 7 males) trimonthly without any modification in symptomatic, or prophylactic drug therapy. Main efficacy variables included number of headache, or migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12-, 24-, and 36-week follow-up. All variables showed a statistically significant improvement at week 36. In general, more than 50 % of patients had a good clinical outcome (including all improved patients, either partial or full responder) and that the percentage of drug abuser patients significantly decreased from 75 to 50 %, thanks to a spontaneous reduction of the symptomatic drug intake. Adverse events were uncommon and did not require treatment discontinuation. Onabotulinum toxin A treatment in refractory CM patients with unsatisfactory prophylactic drug treatments and pharmacological abuse is effective in improving clinical outcome and quality of life. This result may be achieved through a flexible pharmacologic approach tailored to each patient's needs; moreover, the patient himself can be often expected to reduce drug consumption spontaneously. PMID- 27395387 TI - Parkinson's disease and cerebrovascular disease: is there a link? A neurosonological case-control study. AB - Cerebrovascular disease (CVD) and idiopathic Parkinson's disease (PD) frequently occur in the elderly; however, CVD is not frequent in the PD population. The possible relationship between PD and CVD was studied with controversial findings. More specifically, it is unclear whether PD can be protective against the development of vascular disease. To assess the neurosonological examination of a group of PD patients matched with a control group of patients not affected by PD along with the potential risk of developing CVD in the PD group to evaluate any differences. The analysis of the left common carotid artery (CCA) revealed a mean intima-media thickness (IMT) of 0.77 +/- 0.21 mm in the PD group and 0.83 +/- 0.17 mm in the control group, while the right CCA mean IMT was 0.61 +/- 0.17 mm in the PD patients and 0.98 +/- 0.18 mm in the control group. The difference was statistically significant in both sides. PD patients show a lower IMT value in older age (70-80 years) and a reduced cardiovascular risk. PMID- 27395388 TI - Italian normative data for a stroke specific cognitive screening tool: the Oxford Cognitive Screen (OCS). AB - Cognitive deficits occur in most stroke patients and cognitive impairment is an important predictor of adverse long term outcome. However, current screening measures, such as the Mini Mental State Examination or the Montreal Cognitive Assessment, do not provide information tuned for evaluating the impact of cognitive impairment in the early phase after stroke. The Oxford Cognitive Screen (OCS) represents an important new development in this regard. The OCS is now available for assessment of Italian individuals and the aim of this study is to standardize the OCS on a large sample of healthy Italian participants stratified for age, gender and education level. Results confirmed the influence of these factors in several of the OCS tasks. Age-, education- and gender-adjusted norms are provided for the ten sub-tests of the test. The availability of normative data represents an important prerequite for the reliable use of OCS with stroke patients. PMID- 27395389 TI - Evaluation of cytological radiation damage to lymphocytes after I-131 metaiodobenzylguanidine therapy by the cytokinesis-blocked micronucleus assay. AB - OBJECTIVE: The purpose of this study was to evaluate the degree of cytological radiation damage to lymphocytes occurring after I-131 metaiodobenzylguanidine (MIBG) therapy as determined by the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by I-131 in vivo should result in augmentation of the number of cells with micronuclei. METHODS: We studied 15 patients with pheochromocytoma (14/15) or ganglioneuroma (1/15), who were treated initially with 7.4 GBq of I-131-MIBG. Isolated lymphocytes collected from patients 10 days after the therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. Serial blood samples were obtained periodically only from two patients for 2 years after therapy. Micronucleus number of micronuclei per 500 binucleated cells was scored by visual inspection. As controls, lymphocytes from the same patients before the therapy were also studied. In an in vitro study, lymphocytes from eight normal volunteers were exposed to doses varying from 0.5 to 2 Gy and studied with the same method. RESULTS: The mean number (mean +/- SD) of micronuclei after treatment was significantly increased (p < 0.001) as compared to control subjects (49.4 +/- 8.2 vs. 11.3 +/- 6.4). Internal radiation absorbed doses estimated for the 15 patients were 1.6 +/- 0.3 Gy in this external irradiation study. The frequency of micronuclei post-administration of I-131-MIBG gradually decreased to near baseline (i.e., pre-therapy) levels by 2 years. CONCLUSIONS: The relatively low frequency of lymphocyte micronuclei induced by I-131-MIBG in vivo and reversal of the increasing frequency of lymphocyte micronuclei after therapy suggest that the short-term non-stochastic damage induced by this therapy with 7.4 GBq of I-131 MIBG in pheochromocytoma or ganglioneuroma patients is limited and reversible. PMID- 27395391 TI - Path integration in 3D from visual motion cues: A human fMRI study. AB - While neural correlates of path integration on a yaw plane have been studied extensively, much less is known about path integration in three-dimensions (3D). Here we used fMRI during virtual navigation within tunnels in pseudo-3D. We found that the same visual motion stimuli are encoded differently in the brain depending on whether they represent displacements within the yaw plane or within the pitch plane. The yaw plane is more represented in the hippocampus while the pitch plane is more represented in the angular gyrus (AG) and in the posterior inferior temporal gyrus (pITG), known to be involved in 3D space encoding. In addition, a region in pITG, located just above the previous one, showed two different patterns with multi-voxel analysis, separately coding for the pitch and yaw planes. These results suggest that information encoded within pITG about the yaw plane may be exchanged with the hippocampus, while information about the pitch plane may be exchanged with the AG. PMID- 27395390 TI - Neurocognitive Predictors of ADHD Outcome: a 6-Year Follow-up Study. AB - Although a broad array of neurocognitive dysfunctions are associated with ADHD, it is unknown whether these dysfunctions play a role in the course of ADHD symptoms. The present longitudinal study investigated whether neurocognitive functions assessed at study-entry (mean age = 11.5 years, SD = 2.7) predicted ADHD symptom severity and overall functioning 6 years later (mean age = 17.4 years, 82.6 % = male) in a carefully phenotyped large sample of 226 Caucasian participants from 182 families diagnosed with ADHD-combined type. Outcome measures were dimensional measures of ADHD symptom severity and the Kiddie-Global Assessment Scale (K-GAS) for overall functioning. Predictors were derived from component scores for 8 domains of neurocognitive functioning: working memory, motor inhibition, cognitive inhibition, reaction time variability, timing, information processing speed, motor control, intelligence. Effects of age, gender, and pharmacological treatment were considered. Results showed that better working memory predicted lower ADHD symptom severity (R 2 = 3.0 %), and less reaction time variability predicted better overall functioning (higher K-GAS score, R 2 = 5.6 %). Predictors were still significant with baseline behavior included in the models. The role of neurocognitive functioning in the long term outcome of ADHD behavior is discussed. PMID- 27395392 TI - A 7T fMRI study investigating the influence of oscillatory phase on syllable representations. AB - Stimulus categorization is influenced by oscillations in the brain. For example, we have shown that ongoing oscillatory phase biases identification of an ambiguous syllable that can either be perceived as /da/ or /ga/. This suggests that phase is a cue for the brain to determine syllable identity and this cue could be an element of the representation of these syllables. If so, brain activation patterns for /da/ should be more unique when the syllable is presented at the /da/ biasing (i.e. its "preferred") phase. To test this hypothesis we presented non-ambiguous /da/ and /ga/ syllables at either their preferred or non preferred phase (using sensory entrainment) while measuring 7T fMRI. Using multivariate pattern analysis in auditory regions we show that syllable decoding performance is higher when syllables are presented at their preferred compared to their non-preferred phase. These results suggest that phase information increases the distinctiveness of /da/ and /ga/ brain activation patterns. PMID- 27395393 TI - Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants. AB - Cortical folding mainly takes place in the third trimester of pregnancy and may therefore be influenced by preterm birth. The aim of this study was to evaluate the development of specific cortical structures between early age (around 30weeks postmenstrual age) and term-equivalent age (TEA, around 40weeks postmenstrual age) in 71 extremely preterm infants, and to associate this to clinical characteristics and neurodevelopmental outcome at two years of age. First, analysis showed that the central sulcus (CS), lateral fissure (LF) and insula (INS) were present at early MRI in all infants, whereas the other sulci (post central sulcus [PCS], superior temporal sulcus [STS], superior [SFS] and inferior [IFS] frontal sulcus) were only seen in part of the infants. Relative growth from early to TEA examination was largest in the SFS. A rightward asymmetry of the surface area was seen in development between both examinations except for the LF, which showed a leftward asymmetry at both time points. Second, lower birth weight z-score, multiple pregnancy and prolonged mechanical ventilation showed negative effects on cortical folding of the CS, LF, INS, STS and PCS, mainly on the first examination, suggesting that sulci developing the earliest were the most affected by clinical factors. Finally, in this cohort, a clear association between cortical folding and neurodevelopmental outcome at two years corrected age was found, particularly for receptive language. PMID- 27395394 TI - Development of a pharmaceutical cocrystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals. AB - Myricetin shows low oral bioavailability (<10%) in rats due to poor aqueous solubility, although it has demonstrated various pharmacological activities such as those related to anticancer, anti-diabetes, and hepatic protection. To overcome this issue, in this study, pharmaceutical cocrystals were designed to efficiently deliver myricetin by oral administration. A 1:2 stoichiometric cocrystal of myricetin with proline was prepared successfully by solution crystallization based on the ternary phase diagram (TPD) principle, and it is presented as a new sphericity-like crystalline phase characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The formation of myricetin-proline cocrystals was a spontaneous and exothermic process, probably due to the supramolecular interactions between themselves, which were determined by Fourier transform infrared spectroscopy (FT-IR). Consequently, the dissolution efficiency of myricetin from cocrystals was increased 7.69-fold compared with that of coarse myricetin, and the oral bioavailability of myricetin cocrystals in rats was enhanced by approximately 3.03 times compared with that of pure myricetin. The present study provides useful information for the potential application of cocrystal technology for water-insoluble drugs, especially flavonoid compounds. PMID- 27395395 TI - Effect of pH and penetration enhancers on cysteamine stability and trans-corneal transport. AB - Ocular cystinosis is a rare metabolic disorder characterized by the presence of insoluble cystine crystals inside the corneal stroma, with consequent photophobia, keratopathies and frequent corneal erosions. The current therapy consists in the lifetime ophthalmic administration of cysteamine, drug characterized by extremely high hydrophilicity, low molecular weight (77g/mol), and easy oxidization to disulfide. Ocular delivery of cysteamine is very challenging, for its poor permeability and stability in solution. The purpose of the present paper was to study the impact of formulation pH and composition on (1) the trans-corneal delivery and (2) the stability in solution of cysteamine, with particular focus on the use of alpha-cyclodextrin (alpha-CD), benzalkonium chloride (BAC) and disodium edetate (EDTA). Permeation experiments were performed ex vivo through freshly excised porcine cornea; stability was evaluated for six months at -20 degrees , +4 degrees and +25 degrees C; irritation potential was evaluated using HET-CAM assay. The results showed that cysteamine trans-corneal diffusion is strictly dependent on both pH (7.4 preferred to 4.2) and buffering capacity, that negatively impact on the permeation; EDTA did not enhance the trans-corneal diffusion of cysteamine neither at pH 7.4 nor at pH 4.2, while benzalkonium chloride (BAC), antimicrobial agent present within commercial eye drops, significantly enhanced it. Notably, alpha-CD was able to promote the trans corneal diffusion of cysteamine and, at a 5.5%, a 4-fold higher penetration compared to the BAC-containing formulation was obtained. EDTA and acidic pH demonstrated to be essential for cysteamine stability. The formulation obtained by combining alpha-CD and EDTA was characterized by significant permeation, good stability profile, and no irritation potential, even if the tolerability should be further confirmed by in vivo test. PMID- 27395396 TI - Predicting Success of Preliminary Surgical Residents: A Multi-Institutional Study. AB - OBJECTIVE: A nondesignated preliminary surgery (NDPS) position encompasses 1 year of training provided by many general surgery residencies. Our aim was to assess factors predicting success and provide evidence for program directors to support career guidance to preliminary residents. METHODS: Retrospective cohort study of 221 NDPS residents who entered 5 university-based institutions were identified from 2009 to 2013. Records for trainees were reviewed. We defined primary success as obtaining a categorical position in the specialty of choice and secondary success as obtaining a categorical position in any specialty immediately after finishing their NDPS training. Statistical evaluation was performed using chi square analysis, independent t-test and logistic regression using alpha <0.05. RESULTS: Of the 221 NDPS residents, 217 (98%) completed postgraduate year (PGY)-1 and 65 (29%) completed PGY-2. Totally, 90 (41%) obtained categorical general surgery positions, 89 (40%) obtained categorical positions in other specialties, and 42 (19%) failed to obtain a categorical position immediately after their NDPS years. Ultimately, 139 (63%) of residents achieved primary success and 40 (18%) additional residents obtained categorical positions in specialties other than their first choice, resulting in a total of 179 (81%) of residents obtaining categorical positions. Mean United States Medical Licensing Examination step 1 and step 2 scores for those who obtained secondary success were 227 and 234 vs. 214 and 219, respectively, for those who failed to secure a categorical position (p < 0.01). United States Medical Licensing Examination step 2 score was a significant predictor of primary (p < 0.03) and secondary success (p < 0.02). Of 65 PGY-2 NDPS residents, 32 (49%) achieved primary success, and 11 (17%) others achieved secondary success for a total of 43 (66%). For PGY-2 NDPS, American Board of Surgery In-Training Examination was the only significant predictor of primary and secondary success (p < 0.02 and p < 0.05). CONCLUSIONS: NDPS training provides a viable and successful opportunity for at least 81% of young physicians to pursue their career goals even after an unsuccessful first match. PMID- 27395397 TI - Bimanual Psychomotor Performance in Neurosurgical Resident Applicants Assessed Using NeuroTouch, a Virtual Reality Simulator. AB - OBJECTIVE: Current selection methods for neurosurgical residents fail to include objective measurements of bimanual psychomotor performance. Advancements in computer-based simulation provide opportunities to assess cognitive and psychomotor skills in surgically naive populations during complex simulated neurosurgical tasks in risk-free environments. This pilot study was designed to answer 3 questions: (1) What are the differences in bimanual psychomotor performance among neurosurgical residency applicants using NeuroTouch? (2) Are there exceptionally skilled medical students in the applicant cohort? and (3) Is there an influence of previous surgical exposure on surgical performance? DESIGN: Participants were instructed to remove 3 simulated brain tumors with identical visual appearance, stiffness, and random bleeding points. Validated tier 1, tier 2, and advanced tier 2 metrics were used to assess bimanual psychomotor performance. Demographic data included weeks of neurosurgical elective and prior operative exposure. SETTING: This pilot study was carried out at the McGill Neurosurgical Simulation Research and Training Center immediately following neurosurgical residency interviews at McGill University, Montreal, Canada. PARTICIPANTS: All 17 medical students interviewed were asked to participate, of which 16 agreed. RESULTS: Performances were clustered in definable top, middle, and bottom groups with significant differences for all metrics. Increased time spent playing music, increased applicant self-evaluated technical skills, high self-ratings of confidence, and increased skin closures statistically influenced performance on univariate analysis. A trend for both self-rated increased operating room confidence and increased weeks of neurosurgical exposure to increased blood loss was seen in multivariate analysis. CONCLUSIONS: Simulation technology identifies neurosurgical residency applicants with differing levels of technical ability. These results provide information for studies being developed for longitudinal studies on the acquisition, development, and maintenance of psychomotor skills. Technical abilities customized training programs that maximize individual resident bimanual psychomotor training dependant on continuously updated and validated metrics from virtual reality simulation studies should be explored. PMID- 27395398 TI - We Wear Suits and Lie to Each Other. AB - OBJECTIVE: The residency match process is stressful and costly for fourth-year medical students with significant personal and professional implications. We hypothesize that students use impression management (IM) tactics such as conforming to the perceived expectations of program directors and interviewers and to improve their chances of matching. DESIGN: After institutional review board approval, a piloted survey tool was administered to fourth-year medical students at 17 schools. Questions were divided into interviewing behavior categories-slight image creation (embellishing and tailoring), extensive image creation (constructing, inventing, and borrowing), image protection (omitting), and ingratiation (opinion conforming). Descriptive statistics are presented as percentages. Data were analyzed using chi-square test, Fischer exact test, and Bonferroni-adjusted p values where appropriate with statistical significance set at p < 0.05. SETTING: Allopathic medical schools in the United States. PARTICIPANTS: Fourth-year medical students in the United States. RESULTS: The response rate was 21.3%. Respondents were equally male (49.7%)/female (50.3%), primarily 25 to 27-year old (65.9%) and located in the midwest (78.8%). Most attended public medical schools (73.1%). Statistically significant findings are presented in the Tables. CONCLUSIONS: Fourth-year medical students feel the need, and in some instances, actually engage in IM tactics. This study demonstrates that IM tactics are used, and vary by interviewee characteristics. Program directors' awareness of IM tactics may help improving the quality of residency interviews and therefore select more suitable candidates. PMID- 27395399 TI - How Effective are New Milestones Assessments at Demonstrating Resident Growth? 1 Year of Data. AB - OBJECTIVE: Assessment tools that accrue data for the Accreditation Council for Graduate Medical Education Milestones must evaluate residents across multiple dimensions, including medical knowledge, procedural skills, teaching, and professionalism. Our objectives were to: (1) develop an assessment tool to evaluate resident performance in accordance with the Milestones and (2) review trends in resident achievements during the inaugural year of Milestone implementation. DESIGN: A novel venue and postgraduate year (PGY) specific assessment tool was built, tested, and implemented for both operating room and labor and delivery "venues." Resident development of competence and independence was captured over time. To account for variable rotation schedules, the year was divided into thirds and compared using two-tailed Fisher's exact test. SETTING: Brigham and Women's and Massachusetts General Hospitals, Boston MA. PARTICIPANTS: Faculty evaluators and obstetrics and gynecology residents. RESULTS: A total of 822 assessments of 44 residents were completed between 9/2014 and 6/2015. The percentage of labor and delivery tasks completed "independently" increased monotonically across the start of all years: 8.4% for PGY-1, 60.3% for PGY-2, 73.7% for PGY-3, and 87.5% for PGY-4. Assessments of PGY-1 residents demonstrated a significant shift toward "with minimal supervision" and "independent" for the management of normal labor (p = 0.03). PGY-3 residents demonstrated an increase in "able to be primary surgeon" in the operating room, from 36% of the time in the first 2/3 of the year, to 62.3% in the last 1/3 (p < 0.01). CONCLUSION: Assessment tools developed to assist with Milestone assignments capture the growth of residents over time and demonstrate quantifiable differences in achievements between PGY classes. These tools will allow for targeted teaching opportunities for both individual residents and residency programs. PMID- 27395400 TI - Modelling biological evolution: Linking mathematical theories with empirical realities. PMID- 27395401 TI - Mathematical model of galactose regulation and metabolic consumption in yeast. AB - The galactose network has been extensively studied at the unicellular level to broaden our understanding of the regulatory mechanisms governing galactose metabolism in multicellular organisms. Although the key molecular players involved in the metabolic and regulatory processes of this system have been known for decades, their interactions and chemical kinetics remain incompletely understood. Mathematical models can provide an alternative method to study the dynamics of this network from a quantitative and a qualitative perspective. Here, we employ this approach to unravel the main properties of the galactose network, including equilibrium binary and temporal responses, as a way to decipher its adaptation to actively-changing inputs. We combine its two main components: the genetic branch, which allows for bistable responses, and a metabolic branch, encompassing the relevant metabolic processes that can be repressed by glucose. We use both computational tools to estimate model parameters based on published experimental data, as well as bifurcation analysis to decipher the properties of the system in various parameter regimes. Our model analysis reveals that the interplay between the inducer (galactose) and the repressor (glucose) creates a bistable regime which dictates the temporal responses of the system. Based on the same bifurcation techniques, we explain why the system is robust to genetic mutations and molecular instabilities. These findings may provide experimentalists with a theoretical framework with which they can determine how the galactose network functions under various conditions. PMID- 27395402 TI - Therapeutic Potential of Genipin in Central Neurodegenerative Diseases. AB - Central neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are one of the biggest health problems worldwide. Currently, there is no cure for these diseases. The Gardenia jasminoides fruit is a common herbal medicine in traditional Chinese medicine (TCM), and a variety of preparations are used as treatments for central nervous system (CNS) diseases. Pharmacokinetic studies suggest genipin is one of the main effective ingredients of G. jasminoides fruit extract (GFE). Accumulated research data show that genipin possesses a range of key pharmacological properties, such as anti inflammatory, neuroprotective, neurogenic, antidiabetic, and antidepressant effects. Thus, genipin shows therapeutic potential for central neurodegenerative diseases. We review the pharmacological actions of genipin for the treatment of neurodegenerative diseases of the CNS. We also describe the potential mechanisms underlying these effects. PMID- 27395403 TI - Aripiprazole and Acute Extrapyramidal Symptoms in Children and Adolescents: A Meta-Analysis. AB - BACKGROUND: Both the US FDA and the European Medicines Agency (EMA) have approved aripiprazole for use in adolescents for specific indications. Given the assumed favorable side-effect profile of aripiprazole, its use in children and adolescents has increased for both official and off-label indications (anxiety disorders, eating disorders, personality disorders). However, several cases of children and adolescents with new-onset extrapyramidal symptoms (EPS) after commencing treatment with aripiprazole have been reported, and a more systematic appraisal of this possible risk is lacking. OBJECTIVE: We conducted a systematic review and a meta-analysis to assess the evidence for acute EPS (acute dystonia, akathisia, Parkinsonism) associated with the use of aripiprazole in children and adolescents. METHOD: We searched the MEDLINE and Embase databases (2003-10 April 2016) for clinical trials in pediatric patients (aged 0-18 years) using the keywords 'aripiprazole' (regardless of the formulation) and 'extrapyramidal symptoms'. We evaluated the abstracts of papers using the following exclusion criteria: (1) study design: case report, letter to the editor, editorial, or poster presentation data; (2) unrelated PICOS (population, intervention, comparators, outcomes, study) structure. We performed a meta-analysis, in which we used effect sizes with 95 % confidence intervals (CIs). To examine the homogeneity of the effect size distribution, we used a Q-statistic. When we observed heterogeneity in effect sizes, we assessed the possible influence of moderator variables (age and sex, mean dose, study duration, and method of measuring EPS incidence) and evaluated the suitability of either a fixed or a random model. Finally, we assessed the incidence of EPS in children and adolescents treated with aripiprazole compared with placebo. RESULTS: An initial search via PubMed and Embase yielded 328 hits. A manual search of the reference lists of review papers revealed seven additional relevant articles. We included 41 studies, with 2114 pediatric patients, in the meta-analysis. For the analysis of the mean incidence of EPS, data were provided by 24 studies, with a total of 1446 pediatric patients. Meta-analysis revealed a mean EPS incidence of 17.1 % (95 % CI 0.128-0.223). In terms of the incidence of various extrapyramidal side effects, overall, no significant effects of age, sex, mean dose, study duration, or measuring method could be demonstrated. The side effects 'EPS', 'parkinsonism', and 'tremor' were significantly more common in children and adolescents treated with aripiprazole than in those treated with placebo. CONCLUSION: Our meta-analysis provides evidence for a non-negligible incidence of acute EPS in children and adolescents treated with aripiprazole. Although the study has several limitations and further investigation is needed, these findings may help clinicians make more balanced treatment choices and more closely monitor the use of this drug in youth. PMID- 27395404 TI - Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Seizure following traumatic brain injury (TBI) constitutes a common complication that requires effective prevention to improve the outcome of TBI. Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use. Intravenous levetiracetam has been available since 2006 and has been increasingly accepted as a seizure prophylaxis for brain injury, mainly due to its favorable pharmacokinetic features and minimal adverse events profile. However, the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI are not well clarified. OBJECTIVE: The aim of this study was to assess the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI. METHODS: We conducted a search of the MEDLINE, EMBASE, and Cochrane library databases to March 2016, and screened original research that included patients with TBI who received levetiracetam. We included randomized controlled trials (RCTs) or controlled observational cohort studies that compared levetiracetam and phenytoin, as well as uncontrolled case series regarding prophylactic levetiracetam following TBI. The outcomes included early or late seizure prophylaxis and safety. The estimates of seizure prophylaxis were pooled using a meta-analysis, and the estimates for the case series were pooled using descriptive statistics. RESULTS: A total of 1614 patients from 11 studies were included in this review, of whom 1285 patients from eight controlled studies (one RCT and seven cohort studies) were included in the meta-analysis. Levetiracetam was not superior to phenytoin with regard to early seizure prophylaxis (risk ratio [RR] 1.10, 95 % confidence interval [CI] 0.64-1.88); the estimate of early seizure incidence was 0.05 (95 % CI 0.02-0.08). Three studies that assessed late seizure did not indicate the superiority of levetiracetam to phenytoin. There were no differences in mortality during hospitalization or after 6 months, or in the number of patients with adverse reactions between levetiracetam and phenytoin. CONCLUSIONS: Levetiracetam does not appear to be superior to phenytoin in efficacy or safety with regard to early or late seizure prophylaxis following TBI; however, no class I evidence was identified. Additional evidence from high quality studies is required. PMID- 27395405 TI - Gray Matter Atrophy in the Cerebellum-Evidence of Increased Vulnerability of the Crus and Vermis with Advancing Age. AB - This study examined patterns of cerebellar volumetric gray matter (GM) loss across the adult lifespan in a large cross-sectional sample. Four hundred and seventy-nine healthy participants (age range: 7-86 years) were drawn from the Brain Resource International Database who provided T1-weighted MRI scans. The spatially unbiased infratentorial template (SUIT) toolbox in SPM8 was used for normalisation of the cerebellum structures. Global volumetric and voxel-based morphometry analyses were performed to evaluate age-associated trends and gender specific age-patterns. Global cerebellar GM shows a cross-sectional reduction with advancing age of 2.5 % per decade-approximately half the rate seen in the whole brain. The male cerebellum is larger with a lower percentage of GM, however, after controlling for total brain volume, no gender difference was detected. Analysis of age-related changes in GM volume revealed large bilateral clusters involving the vermis and cerebellar crus where regional loss occurred at nearly twice the average cerebellar rate. No gender-specific patterns were detected. These data confirm that regionally specific GM loss occurs in the cerebellum with age, and form a solid base for further investigation to find functional correlates for this global and focal loss. PMID- 27395406 TI - Risk factors for hypernatremia in patients with short- and long-term tolvaptan treatment. AB - PURPOSE: The long-term efficacy of tolvaptan, a vasopressin V2 receptor antagonist, has been reported. However, the safety of long-term treatment remains to be fully elucidated. We assessed the safety profile of tolvaptan with respect to hypernatremia. METHODS: This retrospective study included 371 patients treated with tolvaptan. Risk factors for hypernatremia (serum sodium concentration >=147 mEq/L) were determined. RESULTS: Hypernatremia occurred in 95 patients (25.6 %), of whom 71 (19.1 %) developed hypernatremia within 7 days of tolvaptan treatment (early onset). Stepwise logistic regression analysis demonstrated that baseline serum sodium >=140 mEq/L, an initial tolvaptan dosage >7.5 mg, and a BUN/serum creatinine ratio >=20 were independent risk factors for early onset of hypernatremia. Tolvaptan was prescribed for more than 7 days to 233 patients, of whom 123 were administrated tolvaptan for more than 1 month. Hypernatremia occurred in 24 of these patients (10.3 %) (late onset). Predictive factors for late onset of hypernatremia were an average daily dosage of tolvaptan >7.5 mg and age >=75 years. CONCLUSIONS: A daily dosage of 7.5 mg or less was recommended to prevent hypernatremia in short- as well as long-term tolvaptan treatment, and mainly elderly patients were at risk for hypernatremia. PMID- 27395407 TI - Three novel missense mutations in the filamin B gene are associated with isolated congenital talipes equinovarus. AB - Congenital talipes equinovarus (CTEV) is one of the most common musculoskeletal disorders. Genetic factors have been suggested to be an important contributor to its pathogenesis. Some genes, including PITX1, TBX4, and RBM10, have been associated with CTEV. We aimed to determine the disease-causing mutations in Chinese patients with isolated CTEV. Genomic DNA was extracted from peripheral blood samples of a three-generation pedigree and 53 sporadic patients with CTEV. Whole-exome sequencing and Sanger sequencing were used to identify and validate disease-causing mutations, respectively. A putative pathogenic mutation c.4717G>T (p.D1573Y) in the filamin B (FLNB) gene, which co-segregated with CETV, was identified in the pedigree. Two additional novel missense mutations in the same gene [c.1897A>G (p.M633V) and c.2195A>G (p.Y732C)] were identified from the 53 sporadic patients. Plasmids expressing wild-type or mutant constructs were transfected into HEK293T cells to determine whether these amino acid substitutions affect protein activity. All three (M633V, Y732C, and D1573Y) affected FLNB protein expression and led to cytoplasmic focal accumulation. Our results provide evidence for the involvement of FLNB in the pathogenesis of isolated CTEV and have expanded the clinical spectrum of FLNB mutations. PMID- 27395408 TI - FUS-linked essential tremor associated with motor dysfunction in Drosophila. AB - Essential tremor (ET) is one of the most common adult-onset neurological disorders which produce motor and non-motor symptoms. To date, there are no gold standard pathological hallmarks of ET, and despite a strong genetic contribution toward ET development, only a few pathogenic mutations have been identified. Recently, a pathogenic FUS-Q290X mutation has been reported in a large ET affected family; however, the pathophysiologic mechanism underlying FUS-linked ET is unknown. Here, we generated transgenic Drosophila expressing hFUS-WT and hFUS Q290X and targeted their expression in different tissues. We found that the targeted expression of hFUS-Q290X in the dopaminergic and the serotonergic neurons did not cause obvious neuronal degeneration, but it resulted in motor dysfunction which was accompanied by impairment in the GABAergic pathway. The involvement of the GABAergic pathway was supported by rescue of motor symptoms with gabapentin. Interestingly, we observed gender specific downregulation of GABA-R and NMDA-R expression and reduction in serotonin level. Overexpression of hFUS-Q290X also caused an increase in longevity and this was accompanied by downregulation of the IIS/TOR signalling pathway. Our in vivo studies of the hFUS Q290X mutation in Drosophila link motor dysfunction to impairment in the GABAergic pathway. Our findings would facilitate further efforts in unravelling the pathophysiology of ET. PMID- 27395409 TI - A meta-analysis of HIV and heart rate variability in the era of antiretroviral therapy. AB - BACKGROUND: Heart rate variability (HRV) has been used to assess autonomic dysfunction since the beginning of the HIV epidemic. Although autonomic failure was commonly detected in HIV and AIDS patients prior to the advent of antiretroviral therapy (ART), the effect of HIV on HRV in the current era of widespread ART availability is more ambiguous. METHODS: A systematic search and review was conducted on cross-sectional observational and case-control studies published in the era of ART (1996-2015) that compared HRV between HIV + individuals treated with ART and HIV - controls. Eight out of the 20 studies identified, enrolling a total of 292 HIV + adults (mean age 38.7 years) and 201 HIV seronegative controls (mean age 35.1 years), were included in a meta-analysis based on stringent methodological criteria. RESULTS: At rest, individuals with HIV showed lower HRV in the time (g) = -0.72, 95 % CI (-1.03 to -0.42) and low frequency (LF) domain (g) = -0.51, (-0.81 to -0.21); markers of lower parasympathetic tone in the time (g) = -0.55, (-0.85 to -0.25) and high-frequency (HF) domain (g) = -0.42, (-0.71 to -0.12); and higher LF:HF ratio (g) = 0.46, (0.12-0.86) in the frequency domain, suggestive of parasympathetic withdrawal. CONCLUSION: This meta-analysis confirmed, within a relatively young cohort of HIV + adults on ART, a general reduction in autonomic function with a shift toward sympathetic dominance. This shift may predispose HIV patients to early and elevated risk of arrhythmias, cardiac events, and accelerated HIV disease progression. PMID- 27395410 TI - Effects of olfactory sense on chocolate craving. AB - In the present study, we assessed the effect of the olfactory sense on chocolate craving in college females. Building on previous research by Kemps and Tiggemann (2013), we hypothesized that a fresh scent would decrease one's craving level for chocolate food. While the precursor study only addressed the decrease of chocolate craving, we also hypothesized that a sweet scent would increase one's craving level for chocolate foods. In the present experiment, participants rated their craving levels after viewing images of chocolate foods and inhaling essential oils: one fresh (SliqueTM essence), and one sweet (vanilla). Results supported both of the hypotheses: inhaling a fresh scent reduced females' craving levels; similarly, when a sweet scent was inhaled, the participants' craving levels for chocolate food increased. These findings are particularly beneficial for women seeking weight loss and the findings can be applied in contexts such as weight loss programs, therapy, and maintenance programs, even beyond college settings. The results are particularly useful for helping women regarding stimuli that might serve as triggers for chocolate cravings. PMID- 27395411 TI - A moveable feast: Exploring barriers and enablers to food citizenship. AB - Despite the ability of the globalised food system to deliver varied and plentiful food supplies to most in the developed world it also disconnects consumers from where, how and by whom food is grown, which discourages food citizenship. This paper uses an ecological framework to examine the individual, social, physical and macro-level environments that can positively or negatively influence peoples' engagement with food citizenship. This research used narrative inquiry methodology and purposive sampling to gather stories through focus group conversations. Fifty-two people voluntarily attended focus groups comprised of food procurers from one of five sources: community gardens, Community Supported Agriculture (CSA), farmers' markets, fresh food markets or supermarkets. A narrative was constructed for each of these groups of food procurers; their commonalities and particularities were illuminated through a final interpretive narrative. The findings showed that the community gardeners exhibited a range of personal characteristics that prioritised engagement with local food systems. The physical setting of the community garden enabled the gardeners to make connections to the earth and the people within their social networks. The CSA and farmers' market groups were cognisant of the implications of their food choices and usually proved to be food citizens, as they selected seasonal, local and ethically produced food from their farmer(s). The fresh food market shoppers were ambivalent towards organic and seasonal food and the market setting did not connect them directly to the provenance of their food. The supermarket shoppers' disconnection from those who grew their food and where it was grown disempowered them from making sustainable food choices. Adjustments to the macro-level food environment are needed to enable people to have a greater commitment to food citizenship. PMID- 27395412 TI - Sodium reduction in New Zealand requires major behaviour change. AB - This pilot study examined the feasibility of adherence to a low sodium diet in a sample of healthy New Zealand adults. It also addressed whether following a low sodium diet was accompanied by changes in intakes of other nutrients that influence cardiovascular risk. Eleven healthy adults provided dietary intake data and a 24-hour urine collection at baseline and follow-up. They then received nutritional counselling based on the World Health Organization recommendation for sodium intake (<2000 mg/day) and received ongoing nutritional support while undertaking a low sodium diet for four weeks. At the end of the four-week period, participants completed a semi-structured interview that elicited participants' opinions on barriers and facilitators to following a low sodium diet and explored changes in participants' dietary habits and behaviours. Thematic analysis revealed that adherence to a low sodium diet required substantial changes to participants' usual food purchasing and preparation habits. Participants reported that lack of control over the sodium content of meals eaten away from the home, the complex and time-consuming nature of interpreting nutrition information labels, and difficulty identifying suitable snacks were barriers to adherence. Detailed meal planning and cooking from scratch, using flavour replacements, reading food labels to identify low sodium foods, receiving support from other people and receiving tailored nutrition advice were facilitators. Mean sodium intake reduced over the period, accompanied by a decrease in mean intake of total fat. These factors suggest that sodium reduction in New Zealand adults was feasible. However, considerable changes to eating behaviours were required. PMID- 27395413 TI - Effects of prolonged hypoxia and bed rest on appetite and appetite-related hormones. AB - : Environmental hypoxia and inactivity have both been shown to modulate appetite. To elucidate the independent and combined effects of hypoxia and bed rest-induced inactivity on appetite-related hormones and subjective appetite, eleven healthy, non-obese males underwent three experimental interventions in a cross-over and randomized fashion: 1) Hypoxic confinement combined with daily moderate-intensity exercise (HAMB, FiO2 = 0.141 +/- 0.004; PiO2 = 90.0 +/- 0.4 mmHg) 2) Bed rest in normoxia (NBR, FiO2 = 0.209; PiO2 = 133.1 +/- 0.3 mmHg) and 3) Bed rest in hypoxia (HBR, FiO2 = 0.141 +/- 0.004; PiO2 = 90.0 +/- 0.4 mmHg). A mixed-meal tolerance test (MTT), followed by an ad libitum meal were performed before (Pre) and after 16-days (Post) of each intervention. Composite satiety scores (CSS) during the MTT were calculated from visual analogue scores, while fasting and postprandial concentrations of total ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and leptin were quantified from arterialized-venous samples. Postprandial CSS were significantly lower at Post compared to Pre in NBR only (P < 0.05) with no differences observed in ad libitum meal intakes. Postprandial concentrations and incremental area under the curve (AUC) for total ghrelin and PYY were unchanged following all interventions. Postprandial GLP-1 concentrations were only reduced at Post following HBR (P < 0.05) with resulting AUC changes being significantly lower compared to HAMB (P < 0.01). Fasting leptin was reduced following HAMB (P < 0.05) with no changes observed following NBR and HBR. These findings suggest that independently, 16-day of simulated altitude exposure (~4000 m) and bed rest-induced inactivity do not significantly alter subjective appetite or ad libitum intakes. The measured appetite-related hormones following both HAMB and HBR point to a situation of hypoxia-induced appetite stimulation, although this did not reflect in higher ad libitum intakes. CLINICAL TRIAL REGISTRATION NUMBER: NCT02293772. PMID- 27395414 TI - Recognition of the dense fine speckled (DFS) pattern remains challenging: results from an international internet-based survey. AB - PURPOSE: The dense fine speckled (DFS) pattern as detected by indirect immunofluorescence (IIF) on HEp-2 cells has been associated with several inflammatory diseases but is most commonly observed in individuals that do not have an antinuclear antibody (ANA)-associated rheumatic disease and even in apparently healthy individuals. Consequently, the accurate identification and correct reporting of this IIF pattern is of utmost importance and accordingly has been recognized by several international study groups for the detection of ANA. Furthermore, the DFS IIF pattern has recently been recommended as a competency level recognition pattern by the International Consensus on Antinuclear Antibody (ANA) Pattern (ICAP, http://www.anapatterns.org/ ) Committee. The objective of this study was to use an internet-based survey to assess how accurately the DFS IIF pattern was recognized by experienced technologists. METHODS: High-resolution digital IIF images were captured using the automated IIF NOVA View instrument (Inova Diagnostics, San Diego, CA). Ten images were posted in an anonymous, international, internet-based interpretive survey. Two hundred and thirty IIF technologists were invited to participate. Four of the images in the survey were from previously characterized serum samples with classical ANA IIF patterns (nucleolar, centromere, homogeneous, and speckled) and two of the images were from samples with a DFS IIF ANA pattern and isolated anti-DFS70 antibodies as determined by a chemiluminescence immunoassay. The remaining four images were from sera with the classic IIF ANA patterns referred to above and mixed with a monospecific anti-DFS70-positive sample. The survey included multiple choice selections: homogeneous, DFS, centromere, nucleolar, speckled, other, or unrecognizable. RESULTS: 125 of the 230 participants who completed the survey had diverse levels of experience in IIF pattern recognition on HEp-2 cells ranging from <1 year to >10 years of experience (average >10 years). Participants had a high concordance in correctly classifying the classical ANA IIF patterns: ranging from 95.2 % for centromere to 74.4 % for nucleolar patterns. The unmixed DFS pattern was recognized with significantly lower accuracy (~50 %; p < 0.05). However, less than 10 % correctly identified mixed patterns derived from the sera containing both clinically relevant ANA and anti-DFS70 antibodies. CONCLUSIONS: Recognizing the DFS ANA IIF pattern and mixed IIF patterns composed of DFS + clinically relevant ANA patterns poses a significant challenge. Consequently, it seems imperative that DFS-specific immunoassays should be used to confirm the presence of anti-DFS70 antibodies before definitive results are reported to physicians. PMID- 27395415 TI - PEGylated nanoliposomes encapsulating angiogenic peptides improve perfusion defects: Radionuclide imaging-based study. AB - INTRODUCTION: Although liposomes hold promise for cancer therapy, the effectiveness of treating myocardial ischemia by promoting angiogenesis has yet to be proved. Nanoliposomes loaded with therapeutic agents can effectively target ischemic myocardium via enhanced permeability and retention. Surface polyethylene glycol (PEG) modification can further facilitate effective targeting by prolonging liposomal circulation. This study aimed to determine whether PEGylated nanoliposomes are effective in facilitating targeted drug delivery and treating myocardial ischemia. METHODS: Rats subjected to 30min of myocardial ischemia were given (99m)Tc-hexamethylpropyleneamine oxime- or (99m)Tc-diethylenetriamine pentaacetate-labeled liposomes with mean diameters of ~100nm or ~600nm with or without PEG modifications to determine the extent of myocardial uptake in the different conditions. Therapeutic effectiveness was assessed by studying changes in myocardial perfusion defects with (99m)Tc-tetrofosmin autoradiography and vascular density with immunohistochemistry at 7days post-treatment. RESULTS: The liver and spleen showed the largest capacity for liposome uptake. Uptake by the liver and spleen was more pronounced when the liposomes were larger. Conversely, myocardial liposome uptake was significantly greater when the liposomes were ~100nm rather than ~600nm in diameter. Surface modification with PEG significantly augmented myocardial uptake of ~100nm liposomes. PEG modification did not affect the size dependence. To investigate therapeutic efficacy, hearts subjected to ischemia received PEGylated nanoliposomes encapsulated with angiogenic peptides. Our data demonstrated that PEGylated nanoliposomes loaded with angiogenic peptides improved myocardial perfusion defects and increased vascular density. A 10-fold increase in liposomal concentration did not further benefit myocardial ischemia. CONCLUSIONS: Liposomal angiogenic formulation with size control and PEG modification may be effective treatment strategy for myocardial ischemia. Increasing the concentration of liposomes does not necessarily benefit myocardial ischemia. PMID- 27395416 TI - Correlation of Methylated Circulating Tumor DNA With Response to Neoadjuvant Chemotherapy in Breast Cancer Patients. AB - BACKGROUND: Circulating tumor DNA (ctDNA) is known to harbor tumor-specific genetic or epigenetic alterations. In the present study, the correlation of ctDNA with tumor response to neoadjuvant chemotherapy (NAC) was evaluated in primary breast cancer patients. PATIENTS AND METHODS: Plasma samples were obtained from 87 primary breast cancer patients (stage II-III) before and after NAC, as well as 1 year after surgery. Methylated ctDNA (met-ctDNA) was determined by one-step methylation-specific PCR (OS-MSP) for the promoter region of RASSF1A. RESULTS: The positivity (23.0%, 20/87) of met-ctDNA before NAC was significantly (P < .05) higher than that of carcinoembryonic antigen (CEA) (8.6%) and cancer-associated antigen (CA) 15-3 (7.4%). In the patients with positive met-ctDNA before NAC, met ctDNA significantly decreased after NAC in those with disease that responded to therapy (P = .006), but not in patients whose disease did not respond to therapy. Met-ctDNA after NAC was found to be significantly (P = .008) correlated to the extent of residual tumor burden. Of the 7 patients who showed an increase in met ctDNA at 1 year after surgery, 3 developed recurrence. CONCLUSION: Met-ctDNA is a more sensitive marker than CEA and CA15-3, and it might be useful in monitoring the clinical tumor response to NAC. In addition, the potential use of met-ctDNA as a tumor marker for monitoring postoperative recurrence has been suggested. PMID- 27395417 TI - Biweekly Pegylated Liposomal Doxorubicin (Caelyx) in Heavily Pretreated Metastatic Breast Cancer: A Phase 2 Study. AB - BACKGROUND: Pegylated liposomal doxorubicin (PLD) has shown to be as effective as conventional doxorubicin in the treatment of metastatic breast cancer but provides a lower risk of cardiotoxicity. This phase 2 study in heavily pretreated patients with metastatic breast cancer was initiated to evaluate a biweekly instead of a 4-week schedule of PLD in order to obtain a more flexible and tolerable regimen. PATIENTS AND METHODS: A total of 25 patients with 2 or more prior lines of chemotherapy for metastatic disease were treated with PLD (25 mg/m2) at 2-week intervals for a maximum of 12 courses. Pretreatment with anthracyclines was allowed as long as the cumulative doxorubicin dose at study entry was below 400 mg/m2. Most patients were pretreated with anthracyclines, taxanes, vinorelbine, alkylating agents, and capecitabine. RESULTS: The clinical benefit rate, ie, objective response or stable disease, for at least 6 months was 22.7% for all patients and 22.2% in anthracycline- and taxane-pretreated patients, respectively. Median duration of clinical benefit and median time to progression were 12.5 months (95% confidence interval [CI], 10.1-32.3) and 7 weeks (95% CI, 5.4-8.6), respectively. Median overall survival was 9.6 months (95% CI, 5.4-13.9). One- and 2-year survival rates were 38% and 4%, respectively. Myelosuppression was low, with no grade 3 or 4 neutropenia or thrombocytopenia. Most common nonhematologic toxicities were nausea, alopecia, asthenia, and hand foot syndrome. The low rate of hematologic toxicity and hand-foot syndrome is clinically noteworthy. CONCLUSION: Biweekly PLD is an easily manageable schedule with a favorable toxicity profile. Efficacy was moderate in heavily pretreated patients. PMID- 27395418 TI - Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome. AB - Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of adrenal insufficiency after unilateral adrenalectomy. PMID- 27395419 TI - Mediterranean diet for type 2 diabetes: cardiometabolic benefits. AB - Dietary patterns influence various cardiometabolic risk factors, including body weight, lipoprotein concentrations, and function, blood pressure, glucose-insulin homeostasis, oxidative stress, inflammation, and endothelial health. The Mediterranean diet can be described as a dietary pattern characterized by the high consumption of plant-based foods, olive oil as the main source of fat, low to-moderate consumption of fish, dairy products and poultry, low consumption of red and processed meat, and low-to-moderate consumption of wine with meals. The American Diabetes Association and the American Heart Association recommend Mediterranean diet for improving glycemic control and cardiovascular risk factors in type 2 diabetes. Prospective studies show that higher adherence to the Mediterranean diet is associated with a 20-23 % reduced risk of developing type 2 diabetes, while the results of randomized controlled trials show that Mediterranean diet reduces glycosylated hemoglobin levels by 0.30-0.47 %, and is also associated with a 28-30 % reduced risk for cardiovascular events. The mechanisms by which Mediterranean diet produces its cardiometabolic benefits in type 2 diabetes are, for the most, anti-inflammatory and antioxidative: increased consumption of high-quality foods may cool down the activation of the innate immune system, by reducing the production of proinflammatory cytokines while increasing that of anti-inflammatory cytokines. This may favor the generation of an anti-inflammatory milieu, which in turn may improve insulin sensitivity in the peripheral tissues and endothelial function at the vascular level and ultimately act as a barrier to the metabolic syndrome, type 2 diabetes and development of atherosclerosis. PMID- 27395421 TI - Has the Time Come for All to Routinely Use Intracameral Antibiotic Prophylaxis at the Time of Cataract Surgery? PMID- 27395420 TI - In vitro and in vivo inhibition of mTOR by 1,25-dihydroxyvitamin D3 to improve early diabetic nephropathy via the DDIT4/TSC2/mTOR pathway. AB - We investigated whether 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) could improve early diabetic nephropathy through the DNA-damage-inducible transcript 4/tuberous sclerosis 2/mammalian target of rapamycin pathway. Rat mesangial cells were cultured in media containing normal glucose or high glucose and were treated with or without 1,25(OH)2D3. Mesangial cells proliferation was measured. Streptozotocin-induced diabetic rats were injected intravenously with a recombinant lentivirus against the rat vitamin D receptor gene. Urinary and serum albumin, fasting plasma glucose, serum triglyceride, total cholesterol, calcium, parathyroid hormone and serum 25-dihydroxy-vitamin D (25(OH)D) levels, mean glomerular volume, glomerular basement membrane thickness and total kidney volume were determined. The expressions of vitamin D receptor, DNA-damage-inducible transcript 4, and mammalian target of rapamycin were measured. 1,25(OH)2D3 inhibited the proliferation of mesangial cells induced by hyperglycemia. 1,25(OH)2D3 also significantly reduced albumin excretion, mean glomerular volume, glomerular basement membrane, and total kidney volume in rats with diabetic nephropathy. The expression of DNA-damage-inducible transcript 4 was elevated by 1,25(OH)2D3 treatment. The phosphorylation of mammalian target of rapamycin was reduced by 1,25(OH)2D3 treatment. Vitamin D receptor gene silencing blocked all of the above results. The current study demonstrates that 1,25(OH)2D3 can effectively inhibit mesangial cells proliferation induced by hyperglycemia, thus suppressing the development of diabetic nephropathy. This study also shows that the nephron-protective effect of 1,25(OH)2D3 occurs partly through the DDIT4/TSC2/mTOR pathway. PMID- 27395422 TI - Multivariate analyses of NP-TLC chromatographic retention data for grouping of structurally-related plant secondary metabolites. AB - The chromatographic behavior of 28 plant secondary metabolites belonging to four chemically similar classes (alkaloids, flavonoids, flavone glycosides and sesquiterpenes) was studied by normal-phase thin-layer chromatography (NP-TLC) under 5 different chromatographic systems commonly used in plant drug analysis with the aim to explore whether the retention properties of these metabolites can determine the chemical group they belong to. The use of RM values as the retention parameter is implemented as a relatively new approach in plant analysis. Principal component analysis (PCA), hierarchical clustering heat maps and discriminant analysis (DA), were used for statistical evaluation of the chromatographic data and extraction of similarities between chemically related compounds. The twenty eight metabolites were classified into four groups by principal component analysis. The heat map of hierarchical clustering revealed that all metabolites were clustered into four groups, except for caffeine, while linear discriminant analysis showed that 96.4% of metabolites are predicted correctly as the groupings identified by chemical class in original and cross validated data. The main advantage of the approach described in current paper is its simplicity which can assist with preliminary identification of metabolites in complex plant extracts. PMID- 27395423 TI - Lung Clearance Index in Adults and Children With Cystic Fibrosis. AB - BACKGROUND: Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate end point in cystic fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometric findings. Further study of LCI as an end point in adults with CF is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI across the age range of people with CF. METHODS: Clinically stable adults and children with CF and age-matched healthy control subjects were recruited. RESULTS: LCI and spirometry data for 110 subjects with CF and 61 control subjects were collected at a stable visit. The CF Questionnaire-Revised (CFQ-R) was completed by 80 of 110 subjects with CF. Fifty six subjects with CF completed a second stable visit. The LCI coefficient of variation percent was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (area under the receiving operator characteristic curve [AUCROC] = 0.93 and 0.84, respectively) had greater combined sensitivity and specificity to discriminate between people with CF and control subjects when compared with FEV1 (AUCROC = 0.88 and 0.60, respectively) and forced expiratory flow at 25% to 75% of the curve (AUCROC = 0.87 and 0.68, respectively). LCI correlated significantly with the CFQ-R treatment burden in adults (r = -0.37; P < .01) and children (r = -0.50; P < .01). Washout tests were successful in 90% of subjects with CF and were perceived as comfortable and easy to perform in both adults and children. CONCLUSIONS: These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as in children. PMID- 27395424 TI - Bone SPECT-CT: An additional diagnostic tool for undiagnosed wrist pain. AB - Diagnosis of wrist pain can be difficult to determine with clinical examination and conventional imaging techniques alone. Bone SPECT-CT (single-photon emission tomography with computerized tomography) is a hybrid imaging technique that overlays functional bone scintigraphy in tomographic/3D mode with conventional CT. Data from the two modalities are complementary; areas of abnormal bone metabolism can be localized with anatomical precision, hitherto lacking in conventional bone scans, while structural information from the CT scan further embellishes the diagnostic information. Over the last 6 years, one surgeon (David Evans) has used bone SPECT and later bone SPECT-CT as an additional line of investigation. This is a series of 21 consecutive patients with wrist pain that could not be diagnostically resolved with the usual combination of history, examination, and conventional imaging, and therefore underwent bone SPECT-CT. Clinical and imaging findings, management, and outcomes of these cases are discussed to explore the potential role of this hybrid functional modality in hand and wrist surgical practice. PMID- 27395425 TI - Indications and Results of Reconstructive Techniques with Flaps Transposition in Patients Requiring Complex Thoracic Surgery: A 12-Year Experience. AB - BACKGROUND: Flap transposition is an infrequent but far from exceptional thoracic surgical procedure. The aim of this retrospective study was to report our experience in a referral unit of general thoracic surgery analyzing the early results after flap transposition. METHODS: We retrospectively analyzed the clinical records, surgical notes, and postoperative results of a cohort of patients who underwent flap transposition in our unit from November 2000 to February 2013. RESULTS: Overall, a surgical approach adopting flap reconstruction techniques was performed in 81 patients (54 males, 27 females) with a median age of 62 years (range 20-87). Flap transposition was necessary to reconstruct chest wall after resection for malignancy (27 patients), to repair intrathoracic viscera perforation (15 patients), and to fill residual cavities secondary to pulmonary/pleural infection (39 patients). A pedicle muscle flap was transposed in most of cases (64 pts, 79 %), while in the remaining 17 cases (11 %), an omental flap was used. There were no immediate postoperative complications, while three in-hospital deaths occurred due to respiratory or multiorgan failure. Among patients undergone flap transposition to fill a residual cavity, we observed a recurrent bronchopleural fistula in three patients (7.7 %); such patients were treated by repeat flap transposition (2 cases) and by repeat cavernostomy (1 case). CONCLUSION: Flap transposition may be indicated as part of a multimodal treatment for severely ill patients requiring complex thoracic surgery. PMID- 27395426 TI - Practical Qualitative Research Strategies: Training Interviewers and Coders. AB - The increased emphasis on incorporating qualitative methodologies into nutrition education development and evaluation underscores the importance of using rigorous protocols to enhance the trustworthiness of the findings. A 5-phase protocol for training qualitative research assistants (data collectors and coders) was developed as an approach to increase the consistency of the data produced. This training provides exposure to the core principles of qualitative research and then asks the research assistant to apply those principles through practice in a setting structured on critical reflection. PMID- 27395427 TI - [It is possible to humanize the semen samples collection respecting privacy of subjects? A preliminary report]. PMID- 27395428 TI - Molecular newborn screening of four genetic diseases in Guizhou Province of South China. AB - Genetic disorders have been a major concern for public health in China, especially in the rural regions. However, there is little information available about prevalence of many common single-gene disorders in Guizhou Province in the south western part of China. In the present study, we performed a molecular newborn screening for four genetic disorders, including beta-thalassemia (beta thal), glucose-6-phosphate dehydrogenase (G6PD) deficiency, phenylketonuria (PKU), and non-syndromic hearing loss and deafness (NSHL) in this region. A total of 515 newborns were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) developed for screening the mutations causing these four disorders, and then confirmed by Sanger sequencing. The results showed that 48 out of 515 newborns were carriers of mutations related to these four diseases, with a frequency of 1 in 11 (9.32%). The carrier frequencies for each disease are: beta-thal 2.72%; G6PD deficiency 1.94%; PKU 0.78% and NSHL 4.47%. The genotyping results by MALDI-TOF MS were concordant with Sanger sequencing results within 30 randomly selected samples. This is the first study that reveals carrier frequencies of these four diseases in Guizhou Province. These data provide valuable information for the genetic counseling and disease prevention in Guizhou and southwest China. PMID- 27395429 TI - Computational characterization of TTHA0379: A potential glycerophosphocholine binding protein of Ugp ATP-binding cassette transporter. AB - For the de novo biosynthesis of phospholipids, byproducts such as sn-glycerol-3 phosphate (G3P) and glycerophosphocholine (GPC) of glycerophospholipid metabolic pathway are imported inside the cell by an ATP-binding cassette (ABC) transporter known as UgpABCE. Of which, UgpA and UgpE constitutes the transmembrane domains (TMDs), UgpC forms the dimer of ATP-hydrolyzing component and UgpB is the periplasmic substrate binding protein. Structurally, UgpABCE transporter displays similarity to the maltose ABC transporter of Escherichia coli; thus, has been grouped into the CUT1 (Carbohydrate Uptake Transporter-1) family of bacterial ABC transporters. Being a member of CUT1 family, several Ugp (Uptake glycerol phosphate) protein sequences in biological database(s) exhibit sequence and structure similarity to sugar ABC transporters and have been annotated as sugar binding proteins; one of such proteins is TTHA0379 from Thermus thermophilus HB8. Here, in this study, we used computational method(s) to distinguish UgpB and sugar binding proteins based on their primary and tertiary structure features. A comprehensive analysis of these proteins indicates that they are evolutionarily related to each other having common conserved features at their primary and tertiary structure levels. However, they display differences at their active sites owing to the dissimilarity in their ligand preferences. In addition, phylogenetic analysis of TTHA0379 along with UgpB and sugar binding proteins reveals that both the groups of proteins forms two distinct clades and TTHA0379 groups with UgpB proteins. Furthermore, analysis of the ligand binding pocket shows that all the essential features of glycerophosphocholine binding protein i.e. UgpB, are conserved in TTHA0379 as well. Combining these features, here, we designate TTHA0379 to be a GPC binding protein. PMID- 27395430 TI - Isolation and molecular characterization of a stationary phase promoter useful for gene expression in Gordonia. AB - Gordonia are gram-positive bacteria belonging to Actinomycetes family with a wide variety of industrial and environmental applications. The genetic toolbox, however, is limited for manipulation of these organisms. In the present study, a new promoter has been isolated from Gordonia sp. IITR 100 and characterized in detail. The promoter was found to be functional in Escherichia coli. The minimal promoter was identified in a 166bp fragment by deletion mapping. The putative -35 and -10 hexamer showed four and five nucleotide matches respectively with the E. coli consensus sequence. Three direct repeats and an imperfect inverted repeat upstream to -35 were found. The isolated promoter was found to be six times stronger than the Pkan promoter observed by cloning lacZ downstream to each of them in a plasmid in E. coli. The beta-galactosidase activity was maximum at stationary phase and found to be ~800MU for Gordonia sp. IITR 100 and E. coli. This is the first report of a stationary phase promoter isolated and characterized from Gordonia. PMID- 27395431 TI - Characterization of perfect microsatellite based on genome-wide and chromosome level in Rhesus monkey (Macaca mulatta). AB - Microsatellite studies based on chromosomes level would contribute to the biometric correlation analysis of chromosome and microsatellite applications on the specific chromosome. In this study, the total microsatellite length of 1,141,024 loci was 21.8Mb, which covered about 0.74% of the male Rhesus monkey genome. Perfect mononucleotide SSRs were the most abundant, followed by the pattern: perfect di->tetra->tri->penta->hexanucleotide SSRs. The main range of repeat times focused on 12-32 times (mono-), 7-23 times (di-), 5-10 times (tri-), 4-14 times (tetra-), 4-9 times (penta-), 4-8 times (hexa-), respectively. The largest SSRs number was found in chromosome 1 with 94,347 loci, followed by chromosome 3, 2, 7 and 5, and the smallest number was in chromosome 18. The predominant repeat types in male Rhesus monkey genome and chromosome Y were basically A, AC, AG, AAT, AAC, AAAT, AAAC, AAAG, AAACA and AAACAA. SSRs number of all chromosomes was closely positively correlated with chromosome sequence size (r=0.969, p<0.01), and significantly negatively correlated with abundance (r= 0.24, 0.0130%), and Group 3 with routine direct thrombin inhibitors (DTI) prescription. The cutoff is designed as 300s (290-310s) for Group 1, and 250s (240-260s) for Group 2. With regard to MACE and major bleeding in Group 1, there was no significant difference between higher ACT values and lower ACT values (risk ratio [RR] for MACE, 1.16, 95% confidence interval [CI], 0.65-2.05, p=0.62, I(2)=94%, RR for major bleeding, 0.96, 95% CI, 0.66-1.40, p=0.83, I(2)=0%). Likewise, no significant difference was found in Group 2 between higher ACT values and lower ACT values (RR for MACE, 1.15, 95% CI, 0.97-1.35, p=0.10, I(2)=0%, RR for major bleeding, 0.85, 95% CI, 0.45-1.60, p=0.61, I(2)=83%). In conclusion, ACT may not have a substantial effect on thrombotic or hemorrhagic complications. Under current clinical practice, target ACT may be higher than what is necessary to prevent thrombotic events. We may achieve a relative low ACT level to preserve efficacy and enhance safety. PMID- 27395437 TI - Adequate sleep moderates the prospective association between alcohol use and consequences. AB - OBJECTIVE: Inadequate sleep and heavy alcohol use have been associated with negative outcomes among college students; however, few studies have examined the interactive effects of sleep and drinking quantity in predicting alcohol-related consequences. This study aimed to determine if adequate sleep moderates the prospective association between weekly drinking quantity and consequences. METHOD: College students (N=568) who were mandated to an alcohol prevention intervention reported drinks consumed per week, typical sleep quantity (calculated from sleep/wake times), and perceptions of sleep adequacy as part of a larger research trial. Assessments were completed at baseline and one-, three-, and five-month follow-ups. RESULTS: Higher baseline quantities of weekly drinking and inadequate sleep predicted alcohol-related consequences at baseline and one month follow-up. Significant interactions emerged between baseline weekly drinking quantity and adequate sleep in the prediction of alcohol-related consequences at baseline, one-, three-, and five-month assessments. Simple slopes analyses revealed that weekly drinking quantity was positively associated with alcohol-related consequences for those reporting both adequate and inadequate sleep, but this association was consistently stronger among those who reported inadequate sleep. CONCLUSION: Subjective evaluation of sleep adequacy moderates both the concurrent and prospective associations between weekly drinking quantity and consequences, such that heavy-drinking college students reporting inadequate sleep experience more consequences as a result of drinking. Research needs to examine the mechanism(s) by which inadequate sleep affects alcohol risk among young adults. PMID- 27395439 TI - A Population-Based Analysis of Outcomes in Patients With a Primary Diagnosis of Hypertension in the Emergency Department. AB - STUDY OBJECTIVE: Patients treated primarily for hypertension are common in the emergency department (ED). The outcomes of these patients who were given a primary ED diagnosis of hypertension have not been described at a population level. In this study, we describe the characteristics and outcomes of these patients, as well as changes over time. METHODS: This retrospective cohort study used linked health databases from the province of Ontario, Canada, to assess ED visits made between April 1, 2002, and March 31, 2012, with a primary diagnosis of hypertension. We determined the annual number of visits, as well as the age- and sex-standardized rates. We examined visit disposition and assessed mortality outcomes and potential hypertensive complications at 7, 30, 90, and 365 days and at 2 years subsequent to the ED visit. RESULTS: There were 206,147 qualifying ED visits from 180 sites. Visits increased by 64% between 2002 and 2012, from 15,793 to 25,950 annual visits, respectively. The age- and sex-standardized rate increased from 170 per 100,000 persons to 228 per 100,000 persons during the same period, a 34% increase. Eight percent of visits ended in hospitalization, but this proportion decreased from 9.9% to 7.1% during the study period. Mortality was very low: less than 1% within 90 days, 2.5% within 1 year, and 4.1% within 2 years. Among subsequent hospitalizations for potential hypertensive complications, stroke was the most frequent admitting diagnosis, but the frequency was still less than 1% at 1 year. Together hospitalizations for stroke, heart failure, acute myocardial infarction, atrial fibrillation, renal failure, hypertensive encephalopathy, and dissection were less than 1% at 30 days. CONCLUSION: The number of visits made primarily for hypertension has increased significantly during the last decade. Although some of the increase is due to aging of the population, other forces are contributing to it as well. Subsequent mortality and complication rates are low and have declined. With current practice patterns, the feared complications of hypertension are extremely infrequent. PMID- 27395440 TI - It's all in the past: Deconstructing the temporal Doppler effect. AB - A recent study reported an asymmetry between subjective estimates of future and past distances with passive estimation and virtual movement. The temporal Doppler effect refers to the contraction of future distance judgments relative to past ones. We aimed to replicate the effect using real and imagined motion in both directions as well as different temporal perspectives. To avoid the problem of subjective anchoring, we compared real- and imagined-, ego- and time-moving conditions to a control group. Generally, Doppler-like distortion was only observed in conditions in which the distance between the participant and a frontal target increased. No effects of temporal perspective were observed. The "past-directed temporal Doppler effect" presents a challenge for the current theories of temporal cognition by demonstrating absence of psychological movement into the future. The effect could open new avenues in memory research and serve as a starting point in a systematic examination of how the humans construct future. PMID- 27395441 TI - Young children's preference for unique owned objects. AB - An important aspect of human thought is the value we place on unique individuals. Adults place higher value on authentic works of art than exact replicas, and young children at times value their original possessions over exact duplicates. What is the scope of this preference in early childhood, and when do children understand its subjective nature? On a series of trials, we asked three-year-olds (N=36) to choose between two toys for either themselves or the researcher: an old (visibly used) toy vs. a new (more attractive) toy matched in type and appearance (e.g., old vs. brand-new blanket). Focal pairs contrasted the child's own toy with a matched new object; Control pairs contrasted toys the child had never seen before. Children preferred the old toys for Focal pairs only, and treated their own preferences as not shared by the researcher. By 3years of age, young children place special value on unique individuals, and understand the subjective nature of that value. PMID- 27395442 TI - Differential effects of crude oil on denitrification and anammox, and the impact on N2O production. AB - Denitrification and anammox are key processes for reducing the external nitrogen loads delivered to coastal ecosystems, and these processes can be affected by pollutants. In this study, we investigated the effect of crude oil on denitrification and anammox. Controlled laboratory experiments were performed using sediment slurries from the Lima Estuary (NW Portugal). Anammox and denitrification rates were measured using (15)N-labeled NO3(-), and the production of (29)N2 and (30)N2 quantified by membrane inlet mass spectrometry. Results revealed that while denitrification rates were stimulated between 10 and 25 000 times after crude oil amendment, anammox activity was partially (between 2 and 5 times) or completely inhibited by the addition of crude oil when comparing to rates in unamended controls. Similar results were observed across four estuarine sediment types, despite their different physical-chemical characteristics. Moreover, N2O production was reduced by 2-36 times following crude oil addition. Further work is required to fully understand the mechanism(s) of the observed reduction in N2O production. This study represents one of the first contributions to the understanding of the impact of crude oil pollution on denitrification and anammox, with profound implications for the management of aquatic ecosystems regarding eutrophication (N-removal). PMID- 27395443 TI - Apolipoprotein E4 breaks the association between declarative long-term memory and memory-based orienting of spatial attention in middle-aged individuals. AB - Apolipoprotein (APOE) E4 genotype has been identified as a risk factor for late onset Alzheimer disease (AD). The memory system is mostly involved in AD, and memory deficits represent its key feature. A growing body of studies has focused on the earlier identification of cognitive dysfunctions in younger and older APOE E4 carriers, but investigation on middle-aged individuals remains rare. Here we sought to investigate if the APOE E4 genotype modulates declarative memory and its influences on perception in the middle of the life span. We tested 60 middle aged individuals recruited according to their APOE allele variants (E3/E3, E3/E4, E4/E4) on a long-term memory-based orienting of attention task. Results showed that the APOE E4 genotype impaired neither explicit memory nor memory-based orienting of spatial attention. Interestingly, however, we found that the possession of the E4 allele broke the relationship between declarative long-term memory and memory-guided orienting of visuo-spatial attention, suggesting an earlier modulation exerted by pure genetic characteristics on cognition. These findings are discussed in light of possible accelerated brain ageing in middle aged E4-carriers, and earlier structural changes in the brain occurring at this stage of the lifespan. PMID- 27395444 TI - Predicting transport survival of brindle and red rock lobsters Jasus edwardsii using haemolymph biochemistry and behaviour traits. AB - Mortality events during live transport of Jasus edwardsii rock lobsters are common around the time of season openings in Tasmania, with lobsters from deeper fishing areas with pale shell colouration (brindle) being perceived as more susceptible than shallow-water, red-coloured (red) lobsters. The aims of this study were to assess and predict the vulnerability of brindle and red lobsters to extended emersion exposure using pre- and post-emersion data which included 28 haemolymph biochemical parameters and 5 behaviour traits. No effect of lobster shell colour on haemolymph biochemistry, behaviour traits and their vulnerability to emersion was found. A combined survival of 97% after 40h and 57% after 64h in a first experiment, and 37% after 64h in a second experiment, was observed. Behaviour traits (i.e., righting response, tail flips and three reflex behaviours) were poor indicator of survival. Haemolymph parameters were either unaffected by emersion (e.g., Brix index, protein and lipids), affected by emersion but not associated with mortality (e.g., total haemocyte counts, calcium, magnesium, bicarbonate, glucose and uric acid), or associated with mortality following a recovery period (e.g., pH, the sodium to potassium ratio, urea, and the activity of amylase). A build-up of anaerobic end-products and nitrogenous waste most likely resulted in the mortality. A model based on lobster size and the pre-emersion concentration of haemolymph bicarbonate and haemocyanin was found to be a useful indicator of future survival. This study provides promising leads towards the development of a blood based vulnerability test for live crustacean prior transport. PMID- 27395445 TI - Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Implications for object recognition. AB - Performance was examined on three variants of the spontaneous object recognition (SOR) task, in 5-month old APPswe/PS1dE9 mice and wild-type littermate controls. A deficit was observed in an object-in-place (OIP) task, in which mice are preexposed to four different objects in specific locations, and then at test two of the objects swap locations (Experiment 2). Typically more exploration is seen of the objects which have switched location, which is taken as evidence of a retrieval-generated priming mechanism. However, no significant transgenic deficit was found in a relative recency (RR) task (Experiment 1), in which mice are exposed to two different objects in two separate sample phases, and then tested with both objects. Typically more exploration of the first-presented object is observed, which is taken as evidence of a self-generated priming mechanism. Nor was there any impairment in the simplest variant, the spontaneous object recognition (SOR) task, in which mice are preexposed to one object and then tested with the familiar and a novel object. This was true regardless of whether the sample-test interval was 5min (Experiment 1) or 24h (Experiments 1 and 2). It is argued that SOR performance depends on retrieval-generated priming as well as self-generated priming, and our preliminary evidence suggests that the retrieval generated priming process is especially impaired in these young transgenic animals. PMID- 27395446 TI - High frequency spinal cord stimulation-New method to restore cough. AB - Spinal cord stimulation (SCS, 50Hz) is a useful method to restore an effective cough in persons with spinal cord injury (SCI). However, high stimulus amplitudes and potential activation of pain fibers, significantly limits this application. It is our hypothesis that high frequency SCS (HF-SCS), with low stimulus amplitudes may provide the same level of expiratory muscle activation. In 6 dogs, the effects of SCS, with varying stimulus parameters on positive pressure (P) generation was evaluated. At any given level of stimulus current, mean P was largest at 500Hz, compared to all other stimulus frequencies. For example, with stimulation at 1mA and frequencies of 200, 500 and 600Hz, P were 25+/-3, 58+/-4, 51+/-6cmH2O, respectively. By comparison, P achieved with conventional SCS parameters was 61+/-5cmH2O. HF-SCS results in a comparable P compared to that achieved with conventional stimulus parameters but with much lower stimulus amplitudes. This method may be useful to restore cough even in subjects with intact sensation. PMID- 27395447 TI - Reliability and responsiveness of gait initiation profiles in those with chronic ankle instability. AB - Individuals with chronic ankle instability (CAI) have demonstrated deviations in gait initiation (GI) compared to healthy individuals. However, the intersession reliability of GI measures remains unknown in this population. The objective of this study was to determine the reliability and responsiveness of GI measures between two testing days in those with CAI. Twelve individuals with CAI volunteered. Participants performed barefoot GI on a force plate which captured center of pressure (COP). Data was collected on two separate occasions separated by one week. The GI profile was separated into three phases (S1, S2, and S3). S1 began from the deviation of normal balanced standing to the most posterolateral displacement under the stepping limb. S2 began from the end of S1 to the maximum medial position under the stance foot. S3 began at the end of S2 and continued until the vertical ground reaction force dropped below 100N. COP displacement (cm) was calculated as the sum of resultant vectors of the medial-lateral and anterior-posterior excursions for adjacent COP data points within each phase. The averages of 5 trials were used for analyses. Intraclass correlation coefficients (ICC(2,5)), standard error of measurement, and minimum detectable change (MDC) were calculated to determine reliability and responsiveness. S1, S2, and S3 displacement values were highly reliable between days (ICC(2,5) >=0.76) with the exception of anterior-posterior S1 and medial-lateral S3. MDC values were relatively small (0.6-2.2cm). GI can be reliably assessed in those with CAI which is important for identifying interventions to alter GI profiles in these individuals. PMID- 27395448 TI - Sports-related testing protocols are required to reveal trunk stability adaptations in high-level athletes. AB - Trunk/core stability is considered a key component of training programs, because it could contribute to prevention of low-back and lower-limb injuries and to sports performance. Based on the specificity principle, sports-related trunk stability tests would be required in elite sports performance. However, there may be some generic qualities underlying trunk stability that can be assessed with nonspecific protocols, which are broadly used in sport and rehabilitation. To assess whether specific tests are needed in a high-performance context, we analyzed the influence of specialization in sports with large but qualitatively different balance control demands (judo and kayaking) on trunk stability and compared high-performance athletes with recreational athletes without a specific training history. Twenty-five judokas, sixteen kayakers and thirty-seven recreational athletes performed two trunk stability protocols: sudden loading, to assess trunk responses to external and unexpected perturbations; stable and unstable sitting, to assess the participant's ability to control trunk while sitting. Within-session test-retest reliability analyses were performed to support the between-groups comparison. Judokas showed lower angular displacement (0.199rad) against posterior loading than kayakers (0.221rad) probably because they are frequently challenged by higher sudden loads while they are pushed or pulled. Kayakers showed lower error (<6.12mm) of center of pressure displacements than judokas especially during dynamic task while sitting on an unstable seat (>7.33mm), probably because they train and compete seated on unstable surfaces. Importantly, judokas and kayakers obtained better results than recreational athletes only in those tests designed according to the specific demands of each sport (p<0.050). In conclusion, specific-sport training induces specific trunk stability adaptations, which are not revealed through nonspecific tests. PMID- 27395449 TI - Are there differences in the dual-task walking variability of minimum toe clearance in chronic low back pain patients and healthy controls? AB - The control of minimum toe clearance (MTC, as quantified with its stride-to stride variability during walking) is a promising marker to evaluate motor control. The control of MTC, compared to other gait parameters, was reported to have higher priority. The relationship between the control of MTC and other gait parameters should be examined to elucidate tripping mechanisms. This study aimed at investigating the variability of MTC, stride time and stride length in normal walking and in dual-task walking in back pain sufferers. Twelve patients with chronic low back pain and twelve healthy controls walked with inertial sensors attached on their feet with and without a cognitive dual task. Standard deviations of stride time, stride length and MTC were calculated. Regarding the comparison of dual-task walking in pain patients vs. controls, we found higher variability in stride time in the back-pain group. Higher dual-task walking variability was observed in stride length and stride time only in back pain sufferers. Regarding MTC, however, neither a difference between groups nor between walking conditions were found. We observed that individuals with pain, who generally show higher gait variability, are able to control MTC in a dual task condition indicating that their central nervous system might prioritize control of MTC over other gait parameters. Cases in which also MTC variability increase because of a dual task might characterize alarming fall risk. Dual-task MTC variability should, therefore, be estimated in individuals with severe fall risk as in old individuals with pain, frail people or neurological patients. PMID- 27395450 TI - Three-dimensional evaluation of skeletal deformities of the pelvis and lower limbs in ambulant children with cerebral palsy. AB - Skeletal abnormalities, affecting posture and walking pattern, increase with motor impairment in children with cerebral palsy (CP). However, it is not known whether these skeletal malalignments occur in children with slight motor impairment. Our aim was to evaluate skeletal malalignment at the level of the pelvis and lower limbs in ambulant children with CP, with slight motor impairment, using a low dose biplanar X-ray technique. Twenty-seven children with spastic CP (mean age: 10.9+/-4years, 7 Hemiplegia, 20 Diplegia, GMFCS levels I:17, II:10), with no previous treatments at the hips and knees, underwent EOS((r)) biplanar X-rays. A control group consisting of 22 typically developing children was also included. Three-dimensional reconstructions of the pelvis and lower limbs were performed in order to calculate 11 radiological parameters related to the pelvis, acetabulum and lower limbs. Pelvic incidence and sacral slope were significantly increased in children with CP compared to TD children (48 degrees +/-7 degrees vs. 43 degrees +/-8 degrees , 42 degrees +/-7 degrees vs. 38 degrees +/-5 degrees , respectively, p=0.003). Acetabular parameters did not significantly differ between the two groups. Femoral anteversion and neck shaft angle were significantly increased in children with CP (25 degrees +/-12 degrees vs. 14 degrees +/-7 degrees , p<0.001; 134 degrees +/-5 degrees vs. 131 degrees +/-5 degrees , p=0.005 respectively). No difference was found for tibial torsion. This study showed that even slightly impaired children with CP have an anteverted and abducted femur and present positional and morphological changes of the pelvis in the sagittal plane. The orientation of the acetabulum in 3D seems to not be affected when children with CP present slight motor impairment. PMID- 27395451 TI - Single leg stance control in individuals with symptomatic gluteal tendinopathy. AB - BACKGROUND: Lateral hip pain during single leg loading, and hip abductor muscle weakness, are associated with gluteal tendinopathy, but it has not been shown how or whether kinematics in single leg stance differ in those with gluteal tendinopathy. PURPOSE: To compare kinematics in preparation for, and during, single leg stance between individuals with and without gluteal tendinopathy, and the effect of hip abductor muscle strength on kinematics. METHODS: Twenty individuals with gluteal tendinopathy and 20 age-matched pain-free controls underwent three-dimensional kinematic analysis of single leg stance and maximum isometric hip abductor strength testing. Maximum values of hip adduction, pelvic obliquity (contralateral pelvis rise/drop), lateral pelvic translation (ipsilateral/contralateral shift) and ipsilateral trunk lean during preparation for leg lift and average values in steady single leg stance, were compared between groups using an analysis of covariance, with and without anthropometric characteristics and strength as covariates. RESULTS: Individuals with gluteal tendinopathy demonstrated greater hip adduction (standardized mean difference (SMD)=0.70, P=0.04) and ipsilateral pelvic shift (SMD=1.1, P=0.002) in preparation for leg lift, and greater hip adduction (SMD=1.2, P=0.002) and less contralateral pelvic rise (SMD=0.86, P=0.02) in steady single leg stance than controls. When including strength as a covariate, only between-group differences in lateral pelvic shift persisted (SMD=1.7, P=0.01). CONCLUSION: Individuals with gluteal tendinopathy use different frontal plane kinematics of the hip and pelvis during single leg stance than pain-free controls. This finding is not influenced by pelvic dimension or the potentially modifiable factor of body mass index, but is by hip abductor muscle weakness. PMID- 27395452 TI - Characterizing knee loading asymmetry in individuals following anterior cruciate ligament reconstruction using inertial sensors. AB - Limitations in the ability to identify knee extensor loading deficits during gait in individuals following anterior cruciate ligament reconstruction (ACLr) may underlie their persistence. A recent study suggested that shank angular velocity, directly output from inertial sensors, differed during gait between individuals post-ACLr and controls. However, it is not clear if this kinematic variable relates to knee moments calculated using joint kinematics and ground reaction forces. Heel rocker mechanics during loading response of gait, characterized by rapid shank rotation, require knee extensor control. Measures of shank angular velocity may be reflective of knee moments. This study investigated the relationship between shank angular velocity and knee extensor moment during gait in individuals (n=19) 96.7+/-16.8days post-ACLr. Gait was assessed concurrently using inertial sensors and a marker-based motion system with force platforms. Peak shank angular velocity and knee extensor moment were strongly correlated (r=0.75, p<0.001) and between limb ratios of angular velocity predicted between limb ratios of extensor moment (r(2)=0.57, p<0.001) in the absence of between limb differences in spatiotemporal gait parameters. The strength of these relationships indicate that shank kinematic data offer meaningful information regarding knee loading and provide a potential alternative to full motion analysis systems for identification of altered knee loading following ACLr. PMID- 27395453 TI - What is the best way to radiate the prostate in 2016? AB - Prostate cancer treatment with definitive radiation therapy (RT) has evolved dramatically in the past 2 decades. From the initial 2-dimensional planning using X-rays, advances in technology led to 3-dimensional conformal RT, which used computerized tomography-based planning. This has allowed delivery of higher doses of radiation to the prostate while reducing dose to the surrounding organs, resulting in improved cancer control. Today, intensity-modulated RT (IMRT) is considered standard, where radiation beams of different shapes and intensities can be delivered from a wide range of angles, thus further decreasing doses to normal organs and likely reducing treatment-related toxicity. In addition, image guidance ascertains the location of the prostate before daily treatment delivery. Brachytherapy is the placement of radioactive seeds directly in the prostate, and has a long track record as a monotherapy for low-risk prostate cancer patients with excellent long-term cancer control and quality of life outcomes. Recent studies including several randomized trials support the use of brachytherapy in combination with external beam RT for higher-risk patients. RT for prostate cancer continues to evolve. Proton therapy has a theoretical advantage over photons as it deposits most of the dose at a prescribed depth with a rapid dose fall-off thereafter; therefore it reduces some doses delivered to the bladder and rectum. Prospective studies have shown the safety and efficacy of proton therapy for prostate cancer, but whether it leads to improved patient outcomes compared to IMRT is unknown. Hypofractionated RT delivers a larger dose of daily radiation compared to conventional IMRT, and thus reduces the overall treatment time and possibly cost. An extreme form of hypofractionation is stereotactic body radiation therapy where highly precise radiation is used and treatment is completed in a total of 4 to 5 sessions. These techniques take advantage of the biological characteristic of prostate cancer, which is more sensitive to larger radiation doses per fraction, and therefore could be more effective than conventional IMRT. Multiple randomized trials have demonstrated noninferiority of moderately hypofractionated RT compared to conventional fractionation. There is also a growing body of data demonstrating the safety and efficacy of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer. PMID- 27395454 TI - [Multifunctional Roles of APOE in Alzheimer's Disease Pathogenesis]. AB - Numerous epidemiological studies have shown that the apolipoprotein E gene (APOE) is a strong genetic risk factor for Alzheimer's disease (AD) among people from various ethnic backgrounds. ApoE occurs as three isoforms that differ at two amino acids residues (112 and 158): ApoE epsilon2, epsilon3, and epsilon4. The epsilon4 allele is responsible for a genetic predisposition to AD, increasing the risk of AD by approximately 4-fold compared to the common epsilon3 allele. In contrast, the epsilon2 allele shows a protective effect against AD. APOE epsilon4 is known to affect the age at onset of AD in a dose-dependent manner. In addition to the role of genetic risk, increasing evidence suggests that the substantial effects of APOE genotypes on cognitive function, imaging and biomarker findings, have been reported in cognitively normal individuals in an age-dependent manner. A high frequency of amyloid deposition among cognitively normal, aged individuals carrying the APOE epsilon4 allele has been demonstrated. This suggests that APOE epsilon4 facilitates amyloid deposition during the very early phase of AD pathogenesis. Preventive intervention by using disease-modifying drugs is now being investigated through an exploratory clinical trial for the cognitively normal, aged individuals with the APOE epsilon4 allele. PMID- 27395455 TI - [Age and Sex: Risk Factors for Dementia]. AB - Age- and sex-related differences in the incidence and prevalence of dementia are well-known. These may be affected by other risk factors including metabolic syndrome or diabetes mellitus, dietary habits and apolipoprotein E genotypes. Furthermore, cognitive function could be modulated by sex hormones such as estrogen and androgen via their anti-oxidative, neuro-protective and vasoprotective effects. Contrary to the results from basic research and observational studies, clinical trials on hormone replacement therapy (HRT) have been controversial. Overall, HRT with estrogen plus progesterone in older women seemed to increase the risk of dementia. In contrast, testosterone replacement in older men and dehydroepiandrosterone (DHEA) replacement older women may have potential protective effects on cognitive function, although clinical evidence is insufficient at present. PMID- 27395456 TI - [Epidemiology of Diabetes and Risk of Dementia]. AB - The association between diabetes and the risk of developing dementia has received much attention in epidemiological studies. An accurate population-based prospective cohort study has been conducted in the elderly population of the town of Hisayama in Japan since 1985 aiming to elucidate the secular trends in the prevalence of dementia and examine risk and protective factors for dementia in the Japanese population. The prevalence of all-cause dementia significantly increased from 1985 to 2012. In regard to subtypes of dementia, a similar trend was observed for Alzheimer's disease (AD). In a prospective study of risk factors for dementia in Hisayama elder residents without dementia, diabetes was identified as a significant risk factor for developing all-cause dementia, especially AD. Moreover, 2-hour post-load glucose levels were closely associated with increased risk of all-cause dementia, AD, and vascular dementia. In a pathological study of Hisayama residents, higher levels of 2-hour post-load glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with increased risk of neuritic plaques. The steep increase in the frequency of diabetes could lead to the increasing trend in the prevalence of dementia, especially AD, in the Japanese elderly. PMID- 27395457 TI - [Cardiovascular Disease, as a Risk Factor for Dementia]. AB - Over the past decades, the human lifespan has been increasing. Consequently, the prevalence of age-related diseases including dementia is also on the rise. Recent accumulation of clinical evidence has revealed that dementia is closely associated with cardiovascular disease, such as hypertension and atrial fibrillation. In this paper, we review the current understanding about implications of cardiovascular disease, focusing particularly on the role of hypertension and atrial fibrillation in the development of dementia. PMID- 27395458 TI - [Dyslipidemia and Dementia]. AB - Several lines of evidences support a possible involvement of serum cholesterol in the development of dementia/Alzheimer's disease (AD), with hypercholesterolemia as one of the risk factors that can be targeted by therapeutic interventions. It has also been suggested that statins, prescribed as lipid-lowering drugs to patients at risk for cardiovascular conditions, may be useful in both the prevention and treatment of AD. Currently, conflicting evidences from epidemiological studies indicate a controversial association between dyslipidemia and dementia/AD risk. In randomized clinical trials, virtually no beneficial effect of statin therapy has been observed. On the other hand, in vitro and in vivo animal experiments have revealed that statins suppress amyloid beta protein (Abeta) generation. All these findings suggest that statins can be potentially used as preventive or therapeutic agents for AD. In addition, currently the pathophysiological process of AD is thought to begin many years before the diagnosis of AD dementia. Then, statin treatment as well as some disease modifying therapies may be more efficacious at an early stage of AD including preclinical AD or mild cognitive impairment due to AD. PMID- 27395459 TI - [Post Stroke Dementia]. AB - Post-stroke dementia (PSD) is a clinical entity that encompasses all types of dementia following an index stroke. Current evidence suggests that 25-30% of ischemic stroke survivors develop immediate or delayed vascular cognitive impairment or vascular dementia. The type of stroke can be either ischemic, hemorrhagic or hypoperfusive. There are multiple risk factors for PSD including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischemic attack or recurrent stroke and depressive illness. Pre-stroke dementia refers to the occurrence of cognitive impairment before the index stroke, which may be caused by a vascular burden as well as insidious neurodegenerative changes. Neuroimaging determinants of dementia after stroke include silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Published clinical trials have not been promising and there is little information on whether PSD can be prevented using pharmacological agents. Control of vascular disease risk and prevention of recurrent strokes are key to reducing the burden of cognitive decline and post stroke dementia. Modern imaging and analysis techniques will help to elucidate the mechanism of PSD and establish better treatment. PMID- 27395460 TI - [Depression and Bipolar Disorder: Risk Factors and Potential Prevention of Developing Dementia]. AB - Epidemiological studies have demonstrated that suffering from depression and bipolar disorder may be risk factors for developing dementia. A mechanism of interactions of several factors, such as vascular disease and glucocorticoid, has been speculated to play a role in the development of dementia. It is suggested that the onset of dementia can be prevented or delayed by preventing the onset and recurrence of depression and bipolar disorder. In the prevent of depression, the management of daily life, such as diet and exercise, is important. Recently, the possibility of preventive effects of antidepressants and lithium on developing dementia has been suggested, and a future intervention study is expected. PMID- 27395461 TI - [Apathy and Dementia]. AB - Apathy, which has been attracting attention since Marin's report in 1990, is ubiquitous among neuropsychiatric diseases. It has a major impact on the quality of life in both patients and their caregivers and impairs rehabilitation and outcome. Furthermore, apathy is important as a prodromal syndrome in the development of dementia in mild cognitive impairment (MCI). We reviewed the neurobiological basis, prevalence and assessment of potential benefits of non pharmacologic and pharmacologic interventions for apathy in MCI and dementia. PMID- 27395462 TI - [Sleep Problem as a Prodrome and Risk Factor for Dementia]. AB - Dementia, including Alzheimer's disease, is often associated with various sleep disorders such as insomnia, hypersomnia, circadian rhythm sleep disorders, sleep disordered breathing and sleep debt due to organic damages of sleep/wake promoting nucleus and circadian center (suprachiasmatic nucleus). These sleep disorders reduce the quality of life of individuals with dementia, and increase the care burden, which are major social issues. Recent studies have revealed that sleep deterioration is not only a comorbid symptom but also a prodrome and a risk factor for the development of dementia. PMID- 27395463 TI - [Personality and Dementia]. AB - Previous studies have looked into the relationships between personality and dementia from three hypothetical points of views: 1) that personality type is a risk factor for dementia, 2) that personality changes occur before receiving a diagnosis of dementia, and 3) that premorbid personality traits define behavioral and psychological symptoms of dementia (BPSD) after receiving a diagnosis. This article overviews all three perspectives of the studies, after explaining the character and characteristic attributes of each perspective. PMID- 27395464 TI - [Exercise and Physical Activity for Dementia Prevention]. AB - The effects of exercise and physical activity on cognitive function and brain health have been established by longitudinal and intervention studies. However, it is not clear whether exercise has positive effects on cognitive function in older adults with mild cognitive impairment. Further studies, including a ramdomized controlled trial with a larger sample size, are required to identify the effects of exercise and multicomponent intervention on cognitive function in the older adults with mild cognitive impairment. It is also important to identify the adequate duration, frequency, and intensity of exercise intervention that is most effective for older individuals. PMID- 27395465 TI - [Prevention of Alzheimer's Disease and Nutrients]. AB - The dietary recommendations for the prevention and management of Alzheimer's disease (AD), are the Mediterranean diet and the Japanese-style diet, both of which contain well-balanced nutrients from fish and vegetables. These diets are rich in vitamin E, carotenes, antioxidant flavonoids, vitamin B12, folate, and n 3PUFA. According to recent review supplementation of folate and vitamin E may protect against elderly people's cognitive decline when the serum folate is <12 nmol/L or the vitamin E intake is <6.1 mg/day. Another nutritional topic with regard to dementia and diet is the association of type-2 diabetes and hyperinsulinemia with AD. Expression array data of the brain tissue of AD patients in the Hisayama study strongly suggests a disturbance in insulin signaling in the AD brain. The dysfunction of insulin signaling could directly lead to disrupted glucose utilization in the AD brain. Instead of improperly utilized glucose, the medium chain triglyceride ketone bodies can be an alternative energy resource for the AD brain. In conclusion, the dietary recommendations for the prevention and management of AD are a high consumption of fish, vegetables, and low glycemic index fruits; a moderate amount of meat and dairy products; and a lower amount of carbohydrates and refined sugar. PMID- 27395466 TI - [Alcohol and the Risk of Dementia]. AB - This article reviews studies examining the relationship between alcohol consumption and dementia. Several studies have found that light to moderate alcohol consumption might be associated with decreased dementia risk compared to alcohol abstention. However, not all studies drew the same conclusion and there is no consensus regarding decreased dementia risk related to light to moderate alcohol consumption. The methodological limitations of these studies also need to be considered. For example, definition of alcohol consumption varies with studies. Some studies defined no drinking as never consuming alcohol, while other studies defined it as currently not consuming alcohol. Estimates of dementia risk related to alcohol consumption should be significantly altered by these definitions. Therefore, based on the current evidence, alcohol should not be used as a means to decrease the risk of developing dementia. This article also describes the pathophysiology of alcohol-related dementia, the relationship between Wernicke-Korsakoff syndrome and alcohol-related dementia, clinical characteristics, and the prevalence of alcohol-related dementia. Finally, we document a couple of articles examining the relationship between mortality and alcohol consumption in patients with mild Alzheimer's disease and the impact of alcohol abstention on cognitive decline in patients with Alzheimer's disease. PMID- 27395467 TI - [Do Intellectual Activities Influence Onset of Neurocognitive Disorder?]. AB - In this paper, the author has discussed whether and how intellectual activities influence the onset of neurocognitive disorder based on findings from previous studies. The activities discussed include those involving education and learning during childhood, hobbies and leisure activities with cognitive stimulation, and those through cognitive intervention. There are various opinions on the effect of intellectual activities on the onset of neurocognitive disorder. However, because the relationship between intellectual activities and the onset of neurocognitive disorder has never been fully examined, it seems necessary to discuss this aspect carefully. PMID- 27395468 TI - [Environmental Risk Factors for Dementia]. AB - Owing to recent advancements in imaging techniques and biomarker research, the natural history of Alzheimer's disease (AD) has become clear from the very first preclinical stage. According to the study, more than 20 years before the onset of AD, Abeta starts to accumulate in the brain. This induces neurofibrillary tangle formation in the cerebral isocortex, leading to cognitive decline. If this process is suppressed, disease activity can be controlled. However, at this point, the best and most realistic way to deal with AD is to target the environmental factors that have been identified as risk factors by epidemiological studies. PMID- 27395469 TI - [Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD TBI)]. AB - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease, which is associated with mild repetitive traumatic brain injury (TBI). This long-term and progressive symptom due to TBI was initially called punch-drunk syndrome or dementia pugilistica, since it was believed to be associated with boxing. However, serial neuropathological studies of mild repetitive TBI in the last decade have revealed that CTE occurs not only in boxers but also in a wider population including American football players, wrestlers, and military personnel. CTE has gained large public interest owing to dramatic cases involving retired professional athletes wherein serious behavioral problems and tragic incidents were reported. Unlike mild repetitive TBI, a single episode of severe TBI can cause another type of late-onset neuropsychiatric disease including Alzheimer's disease (AD). Several epidemiological studies have shown that a single episode of severe TBI is one of the major risk factors of AD. Pathologically, both AD and CTE are characterized by abnormal accumulations of hyperphosphorylated tau proteins. However, recent neuropathological studies revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes, and accumulation of other misfolded proteins such as TDP-43. Currently, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can be made only via postmortem neuropathological examination. Development in neuroimaging techniques such as tau and amyloid positron emission tomography imaging might not only enable early diagnosis of CTE, but also contribute to the interventions for prevention of late-onset neurodegenerative diseases following TBI. Further studies are necessary to elucidate the mechanisms of neurodegeneration in the living brain of patients with TBI. PMID- 27395470 TI - [Morphological Re-evaluation of the Basal Ganglia Network]. AB - Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to dopamine signals, via dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of reward prediction error and conducts reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor-critic model has been previously proposed and extended by the existence of role sharing within the striatum, with particular focus on the striosome and matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome and matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID- 27395471 TI - [A Case of Middle Cerebral Artery Stenosis Presented with Limb-Shaking TIA]. AB - Involuntary movement is a rare clinical manifestation of transient ischemic attack (TIA). However, limb-shaking TIA is well described presentation of carotid occlusive disease. We present the case of a patient who developed limb-shaking TIA associated with high-grade stenosis of middle cerebral artery (M1), which was treated with percutaneous transluminal angioplasty (PTA). The procedure was performed successfully without complication and the symptom disappeared immediately after the procedure. The patient remained free of symptoms at the 38 month follow-up. There was no tendency of restenosis of M1. In this case, PTA was technically feasible and beneficial for limb-shaking TIA with M1 stenosis. Limb shaking TIA can be a symptom of high-grade stenosis of M1. PMID- 27395472 TI - Can increased primary care access reduce demand for emergency care? Evidence from England's 7-day GP opening. AB - Restricted access to primary care can lead to avoidable, excessive use of expensive emergency care. Since 2013, partly to alleviate overcrowding at the Accident & Emergency (A&E) units of hospitals, the UK has been piloting 7-day opening of General Practitioner (GP) practices to improve primary care access for patients. We evaluate the impact of these pilots on patient attendances at A&E. We estimate that 7-day GP opening has reduced A&E attendances by patients of pilot practices by 9.9% with most of the impact on weekends which see A&E attendances fall by 17.9%. The effect is non-monotonic in case severity with most of the fall occurring in cases of moderate severity. An additional finding is that there is also a 9.9% fall in weekend hospital admissions (from A&E) which is entirely driven by a fall in admissions of elderly patients. The impact on A&E attendances appears to be bigger among wealthier patients. We present evidence in support of a causal interpretation of our results and discuss policy implications. PMID- 27395473 TI - Glove Contamination during Endodontic Treatment Is One of the Sources of Nosocomial Endodontic Propionibacterium acnes Infections. AB - INTRODUCTION: The opportunistic Propionibacterium acnes recovered frequently from failed endodontic treatments might be the result of nosocomial endodontic infections. The study was aimed to determine if gloves worn by dentists could be one of the sources of these nosocomial infections and to investigate the P. acnes phylotypes involved. METHODS: The cultivable microbiota of gloves (n = 8) at 4 time points (T1, immediately after wearing gloves; T2, after access cavity preparation; T3, after taking a working length/master cone radiograph; and T4, before sealing the cavity) were identified using 16S ribosomal RNA gene sequencing. recA gene sequencing of P. acnes isolates was done. The phylogenetic relationship was determined using MEGA 6 (http://www.megasoftware.net/fixedbugs.html; Megasoftware, Tempe, AZ). Data distributions were compared using the Fisher exact test; means were compared using the Mann-Whitney U test in SPSSPC (version 21; IBM, Armonk, NY). RESULTS: The quantitative viable counts at T4 (aerobically [2.93 +/- 0.57], anaerobically [3.35 +/- 0.43]) were greater (P < .001) than at T1 [(aerobically [0.48 +/- 0.73], anaerobically [0.66 +/- 0.86]) and T2 (aerobically [1.80 +/- 0.54], anaerobically [2.41 +/- 0.71]). Eighty cultivable bacterial taxa (5 phyla) were identified. The most prevalent ones were P. acnes and Staphylococcus epidermidis (100%). recA gene sequencing (n = 88) revealed 2 phylogenetic lineages with type I split into type IA and type IB. Type II was prevalent on gloves. CONCLUSIONS: Contamination of the gloves was detected at the final stages of the treatment. P. acnes and S. epidermidis are the prevalent taxa on gloves and are opportunistic endodontic pathogens. Changing gloves frequently, after gaining access into the pulp space and also after taking the working length/master gutta-percha point radiographs, is likely to reduce the risk of root canal reinfection. PMID- 27395474 TI - Calcium Hydroxide-induced Proliferation, Migration, Osteogenic Differentiation, and Mineralization via the Mitogen-activated Protein Kinase Pathway in Human Dental Pulp Stem Cells. AB - INTRODUCTION: Calcium hydroxide has been extensively used as the gold standard for direct pulp capping in clinical dentistry. It induces proliferation, migration, and mineralization in dental pulp stem cells (DPSCs), but the underlying mechanisms are still unclear. The aim of this study was to investigate the role of the mitogen-activated protein (MAP) kinase pathway in calcium hydroxide-induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs. METHODS: Human DPSCs between passages 3 and 6 were used. DPSCs were preincubated with inhibitors of MAP kinases and cultured with calcium hydroxide. The phosphorylated MAP kinases were detected by Western blot analysis. Cell viability was analyzed via the methylthiazol tetrazolium assay. Cell migration was estimated using the wound healing assay. Alkaline phosphatase (ALP) expression was analyzed using the ALP staining assay. Mineralization was studied by alizarin red staining analysis. RESULTS: Calcium hydroxide significantly promoted the phosphorylation of the c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase. The inhibition of JNK and p38 signaling abolished calcium hydroxide-induced proliferation of DPSCs. The inhibition of JNK, p38, and extracellular signal-regulated kinase signaling suppressed the migration, ALP expression, and mineralization of DPSCs. CONCLUSIONS: Our study showed that the MAP kinase pathway was involved in calcium hydroxide-induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs. PMID- 27395476 TI - A new species of freshwater turtle of the genus Elseya (Testudinata: Pleurodira: Chelidae) from the Northern Territory of Australia. AB - The genus Elseya has had a checkered taxonomic history, but is now restricted to species characterized by an alveolar ridge on the triturating surfaces of the jaw. The Australian forms were once regarded as a single widespread species extending from the Mary River of south-eastern Queensland to the Fitzroy River of north Western Australia, but a number of Australian species have now been identified based on a combination of molecular and morphological data-Elseya dentata, E. irwini, E. lavarackorum and E. albagula. The genus is represented in New Guinea by E. branderhorsti, E. novaeguineae, E. schultzii, and E. rhodini. One additional Australian taxon first identified in 1981 and subsequently established as a distinct taxon by molecular studies, is described here. It is a large chelid turtle that can be distinguished from all other Australian members of the genus Elseya by the distinctive cream or yellow plastron, free of the dark streaking, blotches or suffusing present in other species; an extensive bridge with little or no abrupt angle between the bridge and the ventral surface of the plastron; a head shield broken into a series of small plates rather than a single unit; flat uncornified temporal scales; and a narrower, less robust skull. Osteologically, it can be distinguished from Elseya dentata by the contact of the vomer and the pterygoids. The carapace is typically a light to medium brown in color whereas the carapace of Elseya dentata is typically dark brown to almost black in color. Distribution is the Mary, South Alligator, East Alligator, Goyder and Mann River drainages of the north east of the Northern Territory, Australia. It does not appear to be in sympatry with any other member of Elseya. It is, however, in sympatry with three species of Chelodina, at least two species of Emydura, Myuchelys latisternum and Carettochelys insculpta. PMID- 27395475 TI - A new species of karst forest Bent-toed Gecko (genus Cyrtodactylus Gray) not yet threatened by foreign cement companies and a summary of Peninsular Malaysia's endemic karst forest herpetofauna and the need for its conservation. AB - A new species of Bent-toed Gecko, Cyrtodactylus gunungsenyumensis sp. nov. of the sworderi complex, is described from Hutan Lipur Gunung Senyum, Pahang, Peninsular Malaysia and is differentiated from all other species in the sworderi complex by having a unique combination of characters including a maximum SVL of 74.7 mm; low, rounded, weakly keeled, body tubercles; 34-40 paravertebral tubercles; weak ventrolateral body fold lacking tubercles; 38-41 ventral scales; an abrupt transition between the posterior and ventral femoral scales; 20-23 subdigital lamellae on the fourth toe; enlarged femoral scales; no femoral or precloacal pores; no precloacal groove; wide caudal bands; and an evenly banded dorsal pattern. Cyrtodactylus gunungsenyumensis sp. nov. is a scansorial, karst forest adapted specialist endemic to the karst ecosystem surrounding Gunung Senyum and occurs on the vertical walls of the limestone towers as well as the branches, trunks, and leaves of the vegetation in the associated karst forest. Cyrtodactylus gunungsenyumensis sp. nov. is the seventh species of karst forest adapted Cyrtodactylus and the sixteenth endemic species of karst ecosystem reptile discovered in Peninsular Malaysia in the last seven years from only 12 different karst forests. This is a clear indication that many species remain to be discovered in the approximately 558 isolated karst ecosystems in Peninsular Malaysia not yet surveyed. These data continue to underscore the importance of karst ecosystems as reservoirs of biodiversity and microendemism and that they constitute an important component of Peninsular Malaysia's natural heritage and should be protected from the quarrying interests of foreign industrial companies. PMID- 27395477 TI - A new red-eyed of stream treefrog of Hyloscirtus (Anura: Hylidae) from Peru, with comments on the taxonomy of the genus. AB - We describe a remarkable new species of monophyletic genus Hyloscirtus from northeastern Peru. The presence of an enlarged, curved, and protruding prepollical spine; hypertrophied forelimbs; large, thick supracloacal flap and supratympanic fold; large size; nuptial pad absent and iris dark red diagnose this species. We hypothesize that the new species is closely related to H. condor and H. tapichalaca of southern Ecuador due to the apparently synapomorphic occurrence in these species of an enlarged, curved prepollical spine, and small, conical vomerine odontophore processes with 3-6 prominent teeth each without contact between these. Additional research explicitly incorporating H. diabolus new species in a phylogenetic analysis is required to further test our hypothesis and provide a better understanding of the evolution of morphological attributes described herein. Finally we discuss some aspects concerning the taxonomy of the genus Hyloscirtus. PMID- 27395478 TI - Review of the genus Aulidiotis Meyrick, 1925 (Lepidoptera: Gelechiidae). AB - The genus Aulidiotis Meyrick, 1925 is reviewed. Aulidiotis trimaculata Li, sp. nov., A. recta Li, sp. nov. and A. biloba Li, sp. nov. are described as new. One possibly new species from Hainan is discussed but not formally named for lack of material. Aulidiotis bicolor Moriuti, 1977 is recorded for the first time in China, and A. phoxopterella (Snellen, 1903) is redescribed. Photographs of adults and genitalia are provided, along with a key to all the species of the genus and a map to exhibit the distribution of these species. PMID- 27395479 TI - Barnard's Brachiella sp., Parabrachiella supplicans (Barnard, 1955) and Eubrachiella sublobulata (Barnard, 1955) (Copepoda: Siphonostomatoida: Lernaeopodidae) deposited in the Iziko South African Museum. AB - The family Lernaeopodidae Milne Edwards, is one of the largest families in Siphonostomatoida Thorell, with more than 260 valid species. Brachiella sp., Parabrachiella supplicans (Barnard) and Eubrachiella sublobulata (Barnard) collected from Table Bay by Barnard in 1955 off Liza ramada (Risso), Genypterus capensis (Smith) and Congiopodus torvus (Gronov) respectively, are re-examined. Brachiella sp. is identified as Parabrachiella mugilis (Kabata, Raibaut & Ben Hassine) and is synonymized with Parabrachiella exilis (Shiino) based on the general morphology of the female habitus, the type host and the attachment site on the host. Parabrachiella supplicans is redescribed and synonymized with Parabrachiella genypteri (Capart) also collected off G. capensis from Fort Rock Point, Namibia. Additionally, Eubrachiella sublobulata is redescribed and represents a different geographical range and host record for the genus Eubrachiella as species were previously reported from teleosts of Antarctic waters. PMID- 27395480 TI - Clavadoce (Annelida: Phyllodocidae) from Australia. AB - The first records of the phyllodocid genus Clavadoce are provided from Australia, where the fifth species in the genus is now known: Clavadoce dorsolobata (Hartmann-Schroder, 1987) comb. nov. which is widely distributed in intertidal habitats in southeastern Australia. Clavadoce dorsolobata was described as Eumida (Sige) dorsolobata Hartmann-Schroder, 1987 and herein transferred to Clavadoce. Five species of Clavadoce are now known world wide, four of which are from different regions on the Pacific Ocean margin, while Clavadoce cristata is from the North Atlantic. The Australian species is the first record of Clavadoce for the southern hemisphere. PMID- 27395481 TI - On taxonomic status of Bottchrus, with a description of a new brachypterous species of the genus Trichotichnus (Coleoptera: Carabidae) from the Philippines. AB - Originally described as a separate monotypical genus, Bottchrus Jedlicka, 1935 is treated as a senior synonym of Bellogenus Clarke, 1971, the subgenus of the genus Trichotichnus Morawitz, 1863. The type species of the subgenus Bottchrus, stat. n., Trichotichnus (Bottchrus) philippinus (Jedlicka, 1935), comb. n., is redescribed on the basis of the holotype from the Philippines (without more detailed location) and the new brachypterous species, Trichotichnus (Bottchrus) newtoni sp. n., is described from the series collected in the McKinley Mount, Mindanao, Philippines. The relationships between the brachypterous species of Bottchrus from Ethiopia, the Himalayan region and the Philippines are briefly discussed. The following synonymy is stated: Bottchrus Jedlicka, 1935 = Bellogenus Clarke, 1971, syn. n., = Pseudotrichotichnus Habu, 1973. PMID- 27395482 TI - Two new species of the genus Deltophora Janse, 1950 (Lepidoptera: Gelechiidae). AB - Two Chinese species of the genus Deltophora Janse (Lepidoptera: Gelechiidae), both in obligate mutualism with the plant genus Phyllanthus L. (Phyllanthaceae), are newly described: Deltophora phyllanthicella Li et Sattler sp. n., from Hainan, a pollinator of its larval host Phyllanthus rheophyticus Gilbert et Li; Deltophora polliniferens Li et Sattler sp. n., from Guangdong, a pollinator of its larval host Phyllanthus cochinchinensis (Lour.) Spreng. The adults and the male and female genital structures of both species are described and illustrated. The presence of a fully developed 1st instar larva in the female abdomen of Deltophora phyllanthicella is recorded as the first such case in Gelechiidae. PMID- 27395483 TI - The Shannoniella sisters (Diptera: Rhinophoridae). AB - Shannoniella cuspidata Townsend, 1939 is redescribed and S. setinervis sp. nov. (Brazil, State of Rio de Janeiro) is newly described as its putative sister taxon, thereby allowing for a strict definition of the genus Shannoniella Townsend, 1939 through explicit synapomorphies. An identification key is provided. PMID- 27395484 TI - The first description of the larvae of the Chinese species Paraleuctra tianmushana Li & Yang (Plecoptera: Leuctridae). AB - The pharate larval stage of Paraleuctra tianmushana Li & Yang is described for the first time. The yellowish-brown larvae of this species are characterized by a slender abdomen lacking setae and a unique pattern of dark pigmentation on the head, pronotum, and abdominal terga. Additionally, vestigial cervical gills in this species are present, a character not present in known Nearctic species. PMID- 27395485 TI - Four new species of the genus Mongoliana Distant (Hemiptera: Fulgoromorpha: Issidae) from southern China. AB - Four new species in the planthopper genus Mongoliana Distant from southern China (Hemiptera: Fulgoromorpha: Issidae) are reported. Three of them, M. bistriata sp. nov., M. latistriata sp. nov. and M. albimaculata sp. nov., are described and illustrated; the fourth new one, M. arcuata sp. nov., is briefly described for M. triangularis Chen, Zhang & Chang which was a misidentification of M. triangularis Che, Wang & Chou. M. recurrens (Butler, 1875) is re-described and remarks for its current status is given. A key to all known species of Mongoliana is provided. The distribution and morphological peculiarities of the genus are briefly discussed. PMID- 27395486 TI - First description of leaf-mining Nepticulidae and Tischeriidae (Insecta, Lepidoptera) feeding on the Chilean endemic plant genus Podanthus Lag. (Asteraceae). AB - Despite taxonomic and conservation interest in the Chilean endemic plant genus Podanthus Lag. (Asteraceae: subfamily Asteroideae, tribe Heliantheae), no Podanthus-feeding Nepticulidae or Tischeriidae have ever been recorded. Here, on the basis of material reared from Podanthus from central Mediterranean Chile, we present the description of Stigmella podanthae sp. nov. (Nepticulidae) and a re description of Astrotischeria chilei Puplesis & Diskus, 2003. Females and host plant of the latter species were previously unknown. Both treated species are illustrated with numerous photographs of the leaf-mines, adults of both sexes, and male and female genitalia. PMID- 27395487 TI - Oribatid mites (Acarina, Oribatida) from French Guyana: review of the genus Rhynchoribates and description of three new specie. AB - One new genus (Eurhynchoribates n. gen.) and three new subgenera (Rhynchoribatodes n. subgen., Parhynchoribates n. subgen. and Tectorhynchoribates n. subgen.) are proposed on the basis of review of known species of genus Rhynchoribates Grandjean, 1929 and on the basis of description of three new species-Rhynchoribates (s. str.) danbartai n. sp., Rhynchoribates (Tectorhynchoribates) jurobales n. sp. and Rhynchoribates (Rhynchoribatodes) dynastes n. sp.-from the territory of French Guyana. All known species of Rhynchoribates are discussed and their position into newly defined genera and subgenera proposed. Detailed differential diagnoses are given for all new taxons. PMID- 27395488 TI - New records of ribbon worms (Nemertea) from Ceara, Northeast Brazil. AB - Of 45 species of nemerteans reported for the Brazilian coast, only two were recorded from Brazil's Northeast coast. Here we report seven new records for the state of Ceara, in Northeast Brazil: Tubulanus rhabdotus Correa, 1954, Carinomella cf. lactea Coe, 1905, Baseodiscus delineatus (Delle-Chiaje 1825), Cerebratulus cf. lineolatus Coe, 1905, Cerebratulus sp. 1, Cerebratulus sp. 2 and Lineidae sp. 1. Specimens were collected at the following beaches: Praia dos Dois Coqueiros, Praia do Pacheco, Pecem harbor, Praia da Pedra Rachada and Praia do Guajiru. T. rhabdotus is a new record for Northeast Brazil, Carinomella cf. lactea and Cerebratulus cf. lineolatus are new records for the South Atlantic Ocean and both genera are new records for Brazil. PMID- 27395489 TI - A new record of the freshwater polychaete Namanereis hummelincki
(Polychaeta: Nereididae) from epigean waters of Montserrat. AB - The presence of the freshwater polychaete, Namanereis hummelincki (Augener), on Montserrat is documented for the first time. Although collected in the sediment of a freshwater stream, this subterranean species most likely lives in groundwater aquifers. A mitochondrial cytochrome c oxidase subunit I (COI) sequence obtained from this material supports assignment to the genus Namanereis Chamberlin, and morphological analysis supports identification as N. hummelincki. Differences in jaw morphology observed in the Montserrat specimens may indicate long-term separation from other Caribbean island populations. PMID- 27395490 TI - New records of the genus Diodontus Curtis, 1834 (Hymenoptera: Crabronidae) from Bulgaria, Montenegro and Poland, with a key to Central and Eastern European species. AB - First records of Diodontus medius Dahlbom, 1844 and D. insidiosus Spooner, 1938 from Poland, and of D. handlirschi Kohl, 1888 from Bulgaria and Montenegro are provided. An illustrated key for the identification of Central and Eastern European species of the genus Diodontus is given. PMID- 27395491 TI - A new genus of Braconinae (Hymenoptera: Braconidae) from India with remarkable head ornamentation. AB - A new braconine genus, Stephanobracon Ranjith & Quicke (type-species: Stephanobracon narendrani Ranjith & Quicke sp. nov.) from south India is described and illustrated. It belongs to the tribe Braconini and it displays autapomorphic characters of having two pairs of sharp protuberances near to the antennal sockets and corrugated protuberances on the lateral part of the frons. Its possible relationship to other braconine genera, notably Dolabraulax Quicke, Simra Quicke and Syntomernus Enderlein, is discussed. PMID- 27395492 TI - Two new species and one new record of the genus Asprothrips (Thysanoptera: Thripidae) from China. AB - Two new species of the genus Asprothrips Crawford, A. bucerus sp. n. and A. punctulosus sp. n. are described and illustrated from China. A. bimaculatus Michel & Ryckewaert, previously known only from Martinique in the French West Indies and Malaysia, is newly recorded from mainland China and Taiwan, along with the first descriptive notes of the male, and the record from China of A. fuscipennis Kudo is considered a misidentification of A. bucerus sp. n. The generic diagnosis of Asprothrips is briefly summarized and an updated key to world species of the genus is also presented. PMID- 27395493 TI - Taxonomy of the genus Phymatura J. Sahlberg (Coleoptera: Staphylinidae: Aleocharinae) in the Korean Peninsula. AB - A taxonomic study of Korean Phymatura J. Sahlberg is presented. Three species are recognized, one of which, P. bigranipennis (Bernhauer) comb. nov., is transferred from the genus Atheta Thomson. Pseudatheta gonggaensis (Pace) is restored to the genus Phymatura. Phymatura bigranipennis and P. gonggaensis are identified for the first time in the Korean Peninsula. A key, redescriptions and illustrations of diagnostic characters are provided. PMID- 27395494 TI - Hesperus rougemonti sp. n. (Coleoptera, Staphylinidae) from Borneo. AB - The genus Hesperus Fauvel is, in its current concept, an obviously polyphyletic assemblage. One of the species groups that stand out, due to a combination of characters unusual for Hesperus, is the borneensis group. These characters are the subserrate antennae and the paramere bearing numerous peg setae. Otherwise, the members of this group look as typical for a Hesperus as it can be. At present, the group comprises the following species: H. birmanus Cameron, 1932, H. borneensis Bernhauer, 1915, H. javanus Cameron, 1937, H. malayanus Cameron, 1932a, H. susannekontrusae Schillhammer, 2005, H. temburong Schillhammer, 2002, H. watanabei Shibata, 2002, and H. wemmeri Schillhammer, 2002. PMID- 27395495 TI - A review of Cordylus machadoi (Squamata: Cordylidae) in southwestern Angola, with the description of a new species from the Pro-Namib desert. AB - The girdled lizard genus Cordylus is represented in Angola by two species, Cordylus angolensis and C. machadoi, separated from their nearest congeners by over 700 km. Here we describe a new species, Cordylus namakuiyus sp. nov., endemic to the arid lowlands west of the southern Angolan escarpment. Phylogenetic analysis using three mitochondrial and eight nuclear genes shows that the low-elevation forms and the proximate, high-elevation species C. machadoi are genetically divergent and reciprocally monophyletic, and together form the earliest diverging lineage of the northern Cordylus clade. Morphological data, collected using computed tomography and traditional techniques (scalation and morphology), identify consistent phenotypic differences between these high- and low-elevation species and allows for a detailed description of the osteology and osteodermal arrangements of the new species. A series of 50 specimens, collected during the 1925 Vernay expedition to southwestern Angola and housed at the American Museum of Natural History, are assigned to the new species, although the identity of Cordylus from northern Namibia remains ambiguous and requires further investigation. PMID- 27395496 TI - The genus Anarsia in Cambodia and the Northern Vietnam (Lepidoptera, Gelechiidae), with descriptions of ten new species and a catalogue of the genus in the Central-East Asia. AB - The genus Anarsia Zeller in Vietnam and Cambodia is reviewed, with 19 species including 10 new species: A. deuterodes Park, sp. nov., Anarsia diversiola Park, sp. nov., A. porthmista Park, sp. nov., A. melanodes Park, sp. nov., A. gryphodes Park, sp. nov., A. campestra Park, sp. nov., A. similicampa Park, sp. nov., A. kepensis Park, sp. nov., A. pusillidia Park, sp. nov., and A. houhunlii Park, sp. nov. Nine previously described species, namely A. tricornis Meyrick, A. choana Park, A. isogona Meyrick, A. paraisogona Meyrick, A. incerta Ueda, A. acerata Meyrick, A. didymopa Meyrick, A. phortica Meyrick, and A. patulella (Walker), are reported for the first time from Vietnam or Cambodia. Anarsia magnibimaculata Li & Zheng, 1998 is newly synonymized with A. bimaculata Ponomarenko, 1989. A tentative check list of the genus in the Central and East Asia (including Indochina, China, Russian Far East, Korea, and Japan) is given. PMID- 27395497 TI - Morphological tricks and blessed genitalia: rectifying the family placement of Fijicolana tuberculata (Opiliones: Laniatores: Zalmoxidae). AB - The type specimens of Fijicolana tuberculata Roewer, 1963 were re-examined and the male genital morphology is illustrated and described for the first time. Despite the presence of several morphological features that are typical of Samoidae, such as the presence of scopulae on legs III and IV, genital morphology unambiguously indicates that this species belongs to the Zalmoxidae rather than to the Samoidae. Fijicolana Roewer, 1963 is newly synonymized with Zalmoxis Sorensen, 1886. However, the newly implied combination is preoccupied by Z. tuberculatus Goodnight & Goodnight, 1948 thus the replacement name Zalmoxis roeweri nom. nov. is proposed to avoid secondary homonymy. The definition of Z. roeweri nom. nov. is amended, and the morphology of this species is compared with other representatives of Zalmoxidae and Samoidae. We conclude that the presence of scopulae alone is not a sufficiently diagnostic characteristic for Samoidae and, therefore, correctly placing taxa into families within Samooidea + Zalmoxoidea requires additional morphological evidence (e.g. genital morphology). In light of this result, we point out that the "scopulated" Australasian samoids Badessania metatarsalis Roewer, 1949, Sawaiellus berlandi Roewer, 1949 and Parasamoa gressitti Goodnight & Goodnight, 1957 require re-examination in order to detect potential errors in their family placement. PMID- 27395498 TI - A new species of Scinax Wagler (Anura: Hylidae) from Mato Grosso, Brazil. AB - A new species of the Scinax ruber Clade is described from Municipality of Barra do Garcas, State of Mato Grosso, Brazil. It is diagnosed by its size (SVL 29.4 35.4 mm in males); dorsum with a background that varies from light and dark gray to dark brown, with round and irregular dark blotches; hidden surfaces of thigh and shank light or dark brown, with lighter, large and irregular blotches (yellow in life); and nuptial pad that covers the medial margin of Metacarpal I, and obscures the posterior portion and the outer margin of the inner metacarpal tubercle. It is most similar with Scinax rupestris, from which it differs by having larger adult males; less developed nuptial pad; and hidden surfaces of thigh and light or dark brown, with lighter, large and irregular blotches (yellow in life). The new species occurs near the headwaters of permanent or temporary streams, where males call from vegetation or rocks at the margins of small streams. PMID- 27395499 TI - On the type species of the South American dung beetle genus Chalcocopris Burmeister, 1846 (Coleoptera: Scarabaeidae: Scarabaeinae), with some comments on the type locality of C. hesperus (Olivier, 1789). AB - Recently, a new paper authored by two of us (Rossini & Vaz-de-Mello, 2015) addressed a taxonomic revision of Chalcocopris Burmeister, 1846, describing a second species for the genus and expanding our knowledge of its distribution and morphological diversity. In the present work, we address additional nomenclatural and historical issues not covered in that paper. PMID- 27395500 TI - The advertisement call of Bokermannohyla flavopicta Leite, Pezzuti & Garcia, 2012 (Anura: Hylidae) from the mountains of Chapada Diamantina, Bahia, Brazil. AB - Bokermannohyla Faivovich, Haddad, Garcia, Frost, Campbell & Wheeler (2005) is a Brazilian treefrog genus currently composed of 32 species (Brandao et al. 2012; Leite et al. 2012; Frost 2015). The genus comprehends four, putatively monophyletic, species groups: B. circumdata, B. claresignata, B. martinsi, and B. pseudopseudis (sensu Faivovich et al. 2005). The B. pseudopseudis group includes nine species: B. alvarengai (Bokermann 1956), B. flavopicta Leite et al. 2012, B. ibitiguara (Cardoso 1983), B. itapoty Lugli & Haddad 2006a, B. oxente Lugli & Haddad 2006b, B. pseudopseudis (Miranda-Ribeiro 1937), B. sagarana Leite et al. 2011, B. sapiranga Brandao et al. 2012, and B. saxicola (Bokermann 1964). PMID- 27395501 TI - Chrysura izadiae sp. nov., a new cuckoo wasp (Hymenoptera, Chrysididae) from Southern Iran. AB - Chrysura Dahlbom, 1845 is the second largest genus in the Chrysidini tribe. It is essentially a Holarctic genus composed of over 100 species. The largest diversity is observed in the western Palaearctic Region. Important diagnostic features are the relatively flat and finely punctured face, absence of transverse frontal carina, the edentate metasomal tergum 3, and male flagellomeres 2-5 (especially 2 4) bulging ventrally (Kimsey & Bohart 1991). Kimsey & Bohart (1991) divided Chrysura into five species-groups: candens, cuprea, dichroa, austriaca and radians. Recently, Rosa and Lotfalizadeh (2013) proposed Ch. baiocchii as a new species-group. Within the Ch. dichroa species-group, including about 20 species, the largest richness is observed in the Mediterranean Region where a number of sibling species are present, making taxonomy of this group particularly difficult (Linsenmaier 1959, Arens 2001, 2002). The male genitalia have an important taxonomic value for species identification. The body colour pattern is rather constant in each species-group. All known species in the Ch. dichroa species group have "head blue to green on vertex at least", "pronotal dorsum all or nearly all coppery-red; scutum and scutellum mostly red", "metanotum, propodeum, and pleuron mostly or all purple to green" (Kimsey & Bohart 1991). According to Linsenmaier (1959) the Ch. dichroa species-group has the above body colour with in addition tegula non coppery-red. Up to now, the following seven species belonging to the Ch. dichroa species-group are known in Iran (Rosa et al. 2013, Rosa & Lotfalizadeh 2013, Strumia & Fallahzadeh 2015): Chrysura filiformis (Mocsary, 1889); Ch. laconiae (Arens, 2001); Ch. laevigata (Abeille de Perrin, 1879); Ch. lydiae (Mocsary, 1889); Ch. psudodichroa (Linsenmaier, 1959); Ch. purpureifrons (Abeille de Perrin, 1878); Ch. simuldichroa (Linsenmaier, 1969). PMID- 27395502 TI - Chilocoris laevicollis Horvath, 1919, and Ch. umbricola Linnavuori, 1993-two trogloxenic burrower bugs recorded for the first time in Gabon (Central Africa). AB - First country records of two burrower bugs, Chilocoris laevicollis, and Ch. umbricola (Hemiptera: Heteroptera: Cydnidae) from Gabon (Central Africa) are presented. The study was based on the specimens collected by Dr. V. Aellen, a well-known Swiss speleologist, taken from two caves near Lastoursville in the Gabonese Republic. Diagnostic characters for both recorded species are provided, and data on their biology and distribution are summarized. PMID- 27395503 TI - Description of a new species of Betrichia Mosely 1939 from Brazil and edescription of the type-species (Trichoptera: Hydroptilidae: Leucotrichiinae). AB - Betrichia Mosely 1939 was erected to include a single species, B. zilbra Mosely 1939 from Brazil. The genus has a complicated taxonomy mainly because of the lack of diagnostic characteristics in the original description. Marshall (1979) stated that some features of the antennae, wing venation, and male genitalia are presumably diagnostic, but it remained without a precise diagnosis. Currently, Betrichia comprises 11 Neotropical species (Flint et al. 1999; Olah & Johanson 2011; Thomson 2012; Olah & Flint 2012), six of which have been recorded from Brazil (Santos et al. 2015): B. alibrachia Thomson 2012 (Rio de Janeiro State), B. hamulifera Flint 1983 (Pernambuco, Sao Paulo, and Santa Catarina states), B. kagyla Olah & Flint 2012 (Amazonas State), B. longistyla Flint 1983 (Santa Catarina State), B. varratlana Olah & Flint 2012 (Rondonia State), and B. zilbra Mosely 1939 (Santa Catarina State). Herein, we describe and illustrate a new species of the genus and redescribe the type-species of the genus based on topotypical specimens. We also provide new distributional records for Betrichia zilbra, reported here for the first time from Argentina (Misiones) and Bahia and Sergipe states (Brazil), and for Betrichia bispinosa Flint 1974, representing the first record of this species in Brazil (Amapa and Para states). PMID- 27395504 TI - On the identity of Onthophagus columbianus Boucomont, 1932 (Coleoptera: Scarabaeidae: Scarabaeinae). AB - Onthophagus columbianus Boucomont, 1932 is a new case of transcontinental mislabeling within the genus. The species name is here considered to be new synonym under the Madagascan Onthophagus elegans Klug, 1832. Historical notes, lectotype designations and illustrations of the primary type specimens of both species are provided. PMID- 27395505 TI - The centipedes of Peloponnisos and first records of genus Eurygeophilus in the East Mediterranean (Myriapoda: Chilopoda). AB - In this paper we summarize and critically revise the literature records of the centipedes of Peloponnisos in mainland Greece. Moreover, records on recently collected material in East Peloponnisos are included with a special focus on Mount Parnonas. Fifty centipede species are listed (1 Scutigeromorpha, 20 Lithobiomorpha, 6 Scolopendromorpha and 23 Geophilomorpha) belonging to 21 genera, 9 families and 4 orders. The species Eurygeophilus multistiliger (Verhoeff, 1899) is here reported for the first time not only from Greece but also from the East Mediterranean and the Balkan Peninsula. Additionally, the species Geophilus insculptus Attems, 1895, Stenotaenia rhodopensis (Kaczmarek, 1970) and Henia pulchella (Meinert, 1870) are newly recorded from Peloponnisos. Synonyms, general geographic distribution, patterns of distribution (chorotype), literature records, material examined from Mt. Parnonas, and ecological information (such as altitudinal ranges and habitat preferences) are given for each species. Remarks are additionally provided for some species and maps of species distribution in Peloponnisos are presented. PMID- 27395506 TI - Catalogue of families and their type genera in the mite suborder Uropodina (Acari: Mesostigmata). AB - This paper reviews 47 names that have been used at the levels of Family, Subfamily and Tribe, for mites in the suborder Uropodina. Complete bibliographic references are provided for all of these names and the names of their type genera. The spelling and authorship of taxon names is corrected where necessary. Fifteen of these family-group names are unavailable, because they do not satisfy the requirements of the International Code of Zoological Nomenclature. However, some of these names represent taxonomic concepts that may be useful in future revisions of the group. PMID- 27395507 TI - New species and records of phytoptid mites (Acari: Eriophyoidea: Phytoptidae) on sedges (Cyperaceae) from the Russian Far East. AB - Two new phytoptine species, Oziella virgata n. sp. and O. ovalis n. sp., were collected from the Russian Far East on sedges, Carex appendiculata (Trautv. & C.A. Mey) Kukenthal and Kobresia myosuroides (Villars) Fiori, respectively, and are described herein using conventional light microscopy (LM) and confocal laser scanning microscopy (CLSM). In addition, Oziella cf. rigida (Roivainen 1950) was recorded from Carex scita var. riishirensis (Franch.) Kuk. in the Kamchatka Peninsula whilst Novophytoptus rostratae Roivainen 1947 was found on Carex saxatilis L. and C. appendiculata in the Sakha Republic (Yakutia) of Russia and Carex soczavaeana Gorodkov on the Kamchatka Peninsula. Oziella virgata n. sp. has a unique rod-like seta u' on the medial-lower surface of tarsi I & II, a character not previously described in eriophyoid mites. Additionally, the position of setae 3a in nymphs and females differs: these are located on the same annulus as tubercles of setae c2 in nymphs whereas in females, those are situated notably ahead of tubercles c2 (closer to coxae II). Males of O. virgata n. sp. possess a well-developed genital coverflap, resembling that of Mackiella reclinata Chetverikov & Craemer, 2014, Pentasetacus araucariae (Schliesske, 1985) and Loboquintus subsquamatus Chetverikov & Petanovic, 2013. The original slidemounted specimens of the new Oziella species described herein were inappropriate for LM study. However, CLSM microscopy images obtained prior to remounting were sharp enough for diagnostic purposes indicating that this is a useful method for studying poor quality specimens which may otherwise be difficult to remount or, in some cases, are very rare. PMID- 27395508 TI - Molecular systematics and taxonomic status of three latitudinally widespread nototheniid (Perciformes: Notothenioidei) fishes from the Southern Ocean. AB - The taxonomic status of the three nototheniids, Lepidonotothen squamifrons, L. larseni and Gobionotothen marionensis from different localities in the Southern Ocean is re-evaluated at the DNA level. DNA sequence divergences and phylogenetic relationship were estimated using a combined mitochondrial (mtDNA, ND2 and COI) dataset and data for one nuclear gene (S7 intron 1). Phylogenies of both datasets had Lepidonotothen kempi nested within L. squamifrons lineage, with low sequence divergences (0% to 0.4%) between the two nominal species suggesting that they are populations of one species. Therefore, these results do not support the previous splitting of L. squamifrons into different species. Similarly, the L. larseni specimens also represented a single genetic unit (0.3% to 0.6%) with low geographic variation between Atlantic and Indian Ocean specimens, which does not support the splitting of this species into geographically restricted species. The mtDNA phylogeny clearly separated individuals of G. acuta from Kerguelen, Heard and MacDonald Islands from G. marionensis individuals into different clades, with sequence divergence of 2.9% between these clades supporting they are different species. PMID- 27395509 TI - The Lepidostoma coreanum Species Complex (Trichoptera, Lepidostomatidae) in the Asian Far East. AB - A total of 68 species of genus Lepidostoma Rambur (Trichoptera; Lepidostomatidae) has been reported from the Asian Far East. L. coreanum (Kumanski & Weaver 1992) was originally described from North Korea. Detail examination of specimens of this species and its related specimens collected in the Asian Far East revealed the hypothetical definition of L. coreanum and the presence of 4 new related species, L. niigataense sp. nov., L. hattorii sp. nov., L. yuwanense sp. nov., and L. ishigakiense sp. nov. The species assemblage is named as the Lepidostoma coreanum Species Complex. PMID- 27395510 TI - A new species of dwarf gecko in the genus Lygodactylus (squamata: Gekkonidae) from central Kenya. AB - A new species of Lygodactylus gecko (L. wojnowskii sp. nov.) is described from the vicinity of Chogoria Town on the eastern lower slopes of Mt. Kenya in central Kenya. A phylogeny based on mitochondrial and nuclear DNA shows that the proposed new taxon is distinct within the Lygodactylus picturatus group and is the sister lineage to L. mombasicus and L. kimhowelli. It is morphologically very similar to both L. mombasicus and L. keniensis but its dorsal coloration and pattern is different. Its dorsum is grey with dark stripes while its head has black and white stripes that form a Y-shaped mark. While the male throat pattern is similar to that of L. mombasicus, that of the female is like that of females and some males of Lygodactylus keniensis. Lygodactylus wojnowskii sp. nov. has a higher number of post-postmental scales (6) than do its close relatives (5). The new species is distributed on the lower slopes of mid-altitude areas on eastern Mt. Kenya, but it may occur in other areas at similar elevations in central Kenya. It is associated with short, scattered trees within agricultural areas. It has not yet been recorded within the protected Chogoria forest block of Mt. Kenya forest. It is likely present in Mwea National Reserve as it occurs in nearby areas. PMID- 27395511 TI - Two new species of Allonychiurus Yoshii, 1995 (Collembola, Onychiuridae) from eastern China, with a key to world species of the genus. AB - Two new species, Allonychiurus zhejiangensis sp. nov. and Allonychiurus pseudokimi sp. nov., have been reported from eastern China. A. zhejiangensis sp. nov. is particular in the genus as having three pso on ventral side of the head. A. pseudokimi sp. nov. is similar to A. kimi, but they can be distinguished by the number of pso on ventral side of the head, the number of chaetae along axial line on Abd. I-II, the number of chaetae on ventral tube and the presence of basal lamella on unguiculus. A key to the known species of the genus all over the world is given accordingly. PMID- 27395512 TI - A new dromiid crab (Crustacea, Brachyura, Dromioidea) from the Upper Eocene of Huesca (Aragon, northern Spain). AB - A new genus and species of brachyuran crab from the Upper Eocene (Priabonian) strata in Basa Valley (Huesca, northern Spain) assignable to the superfamily Dromioidea, Basadromia longifrons n. gen., n. sp., adds to current knowledge of the morphological diversity and geographical-stratigraphical distribution of the superfamily. The main characters of the new form, such as the orbitofrontal construction with two median teeth and an rostral tooth situated in a lower plane, two minor frontal (inner orbital) teeth, well-marked cervical and branchial grooves, general carapace outline, and the shape and distribution of dorsal regions, confirm placement in Dromioidea. Unique features, such as the four conspicuous frontal teeth, lateral margins of carapace with small, subtle spines, the reduced length of the posterior margin, disposition of dorsal grooves, and peculiar shape and distribution of the dorsal regions (mainly protogastric and epibranchial), warrants the erection of a new genus and new species. In the absence of ventral features the new taxon is tentatively assigned to the family Dromiidae after detailed comparison with both fossil and extant members. PMID- 27395513 TI - Australomesitius gen. nov. (Hymenoptera, Bethylidae: Mesitiinae), an unexpected new genus from Australia. AB - Mesitiinae include 218 species classified in 21 genera. Hitherto all species are confined to Old World (Afrotropical, Oriental and Palaearctic Regions). However most of their species are reported from Mediterranean areas, and few species are recorded from Northern areas of Palaearctic Asia. While visiting Queensland Museum Daniele Mugrabi sort part of it wet collection and got a bizarre specimen, which represents an undescribed genus of Mesitiinae. Besides, this specimen has the body surface densely punctate, characteristic never recorded to Mesitiinae species, and a combination of characters which does not fit any of the known genera Mesitiinae. The primary aim of this work is to describe this new genus, as well as to compare it with the other genera of the Mesitiinae. PMID- 27395514 TI - Annotated checklist of millipedes (Myriapoda: Diplopoda) of Sri Lanka. AB - This review lists the currently known species of millepedes in Sri Lanka and discusses their current taxonomic status and distribution based on previous studies from 1865 to date. A total of 104 millipede species belonging to 44 genera, 18 families and nine orders have been recorded in Sri Lanka. Of these, 82 are known only from Sri Lanka; additionally, nine genera and one family are known only from Sri Lanka. Most of the millipede species have been recorded from two localities, namely Pundaluoya and Kandy in the central highlands of Sri Lanka. Current knowledge on the taxonomy, evolutionary relationships, distribution and conservation of the millipedes of Sri Lanka is still limited and scattered. Thus we suggest more intensive surveys to acquire comprehensive data on the millipedes of Sri Lanka. PMID- 27395515 TI - Two new species and new records of chiggers (Acari: Leeuwenhoekiidae,
Trombiculidae) from birds in Vietnam. AB - A total of 12 chigger species (Acariformes: Trombiculidae) occurred on 7 bird species in Vietnam. Two new species, namely Neoschoengastia vietnamensis sp. nov. and Hypogastia stekolnikovi sp. nov. are described, figured and compared with similar species placed in relevant genera using differential diagnoses of related species. Figures and diagnosis of Leptotrombidium taiyuanense Tian and Wen, 1984 are added. Odontacarus audy (Radford, 1946), Leptotrombidium allosetum Wang, Liao and Lin, 1981, L. taiyuanense, Leptotrombidium hanseni Traub and Lakshana, 1966, Leptotrombidium kunshui Wen and Xiang, 1984, Leptotrombidium paradux Vercammen Grandjean and Langston, 1976, Leptotrombidium turdicola Vercammen-Grandjean and Langston, 1976, Neotrombicula elegans Schluger, 1966 and Neoschoengastia longitar salis Schluger and Belskaya, 1966 were recorded in Vietnam for the first time. PMID- 27395516 TI - A contribution to the knowledge of the subfamily Panagaeinae Hope, 1838
from Africa. Part 1. Revision of the Craspedophorus reflexus group (Coleoptera: Carabidae). AB - Afrotropical species of the Craspedophorus reflexus group are revised. C. arnosti sp. n. (Central Africa), C. ruvumanus sp. n. (Ruvuma Region, Tanzania) and C. reflexus megamacula ssp. n. (Senegambia) are described. Craspedophorus reflexus group sensu Chaudoir, 1879 is redefined and C. savagei (Hope, 1842) is synonymized with C. reflexus (Fabricius, 1781). PMID- 27395517 TI - Chulacaridae, a new family of prostigmatic mites (Acari, Trombidiformes)
from Thailand. AB - A new family of prostigmatic mites (Acari: Trombidiformes), Chulacaridae n. fam. based on Chulacarus elegans n. g. et n. sp., is described from adult females and immature instars collected from soil and litter in Thailand. The new family is monobasic and is placed in the hyporder Anystae (sensu Zhang et al. 2011), and tentatively grouped with other families in the superfamily Anystoidea. In addition to the typical features of Anystina, Chulacaridae n. fam. is characterized by the presence of enlarged, raptorial legs I uniquely with bipectinate setae on their anterior face, the presence of thick and blunt adoral setae (or1 and or2), the fusion of the palpal femur and genu, the absence of any femoral subdivision of legs I-IV, the presence of 8-10 pairs of small genital papillae, and the presence of unipectinate claws (without empodium) on pretarsi I and normal claws (with claw-like empodium) on pretarsi II-IV. Some morphological characters and its systematic position are discussed. PMID- 27395518 TI - Eriophyoid mites from Eastern India: description of three new species (Acari: Prostigmata: Eriophyoidea). AB - Three new eriophyoid mite species, namely Dichopelmus puncti n. sp. (Eriophyidae) from cogan grass, Imperata cylindrica (Poaceae); Calacarus kalyaniensis n. sp. (Eriophyidae) from Siam weed, Chromolaena odorata (Asteraceae) and Neorhynacus bidhanae n. sp. (Diptilomiopidae) from Croton caudatus (Euphorbiaceae), are described and illustrated from West Bengal, India. The new species are vagrants on the leaves of their respective host plants with no visible damage observed. Keys to the known species of Dichopelmus and Neorhynacus are provided along with a checklist of eriophyoid mites species present in West Bengal. PMID- 27395519 TI - A new genus Carinopius gen. n. of the subfamily Opiinae (Hymenoptera,
Braconidae) from China and Vietnam, with description of a new species. AB - Carinopius gen. n. (type species: Carinopius albocoxalis Tan & van Achterberg, sp. n.) from China (Yunnan) and Vietnam is described and illustrated (Hymenoptera: Braconidae: Opiinae). PMID- 27395520 TI - Two new species of the ant-eating spider genus Tropizodium Jocque & Churchill, 2005 (Araneae, Zodariidae, Zodariinae) from India. AB - Two new species, Tropizodium kalami sp. n. and Tropizodium viridurbium sp. n. from the genus Tropizodium are described from India. Detailed morphological descriptions, diagnostic features and illustrations of copulatory organs are given. Distribution of both the new species is mapped. PMID- 27395521 TI - Descriptions of the mature larvae for two species of Pseudopyrochroa from Taiwan (Coleoptera: Pyrochroidae: Pyrochroinae), with notes on their natural history. AB - Field collections and rearing have established the first species-level associations for larvae of Pyrochroidae from Taiwan. Larvae of Pseudopyrochroa carinifrons and Pseudopyrochroa fainanensis were collected from beneath bark and in coarse, decaying woody debris of dead logs and successfully reared to the respective adult stages. The mature larvae are described and salient features are illustrated. Notes on larval habitats and natural history are also provided. PMID- 27395522 TI - Loricophrya bosporica n. sp. (Ciliophora, Suctorea) epibiont of Desmoscolex minutus (Nematoda, Desmoscolecida) from oxic/anoxic boundary of the Black Sea Istanbul Strait's outlet area. AB - A suctorian ciliate Loricophrya bosporica sp. nov. is described from the body surface of nematodes of genus Desmoscolex collected in oxic/anoxic boundary of the Bosporus outlet area of the Black Sea. The new species differs from relative species L. sivertseni by development of its body, which takes no more than half, or a third of the lorica length, absence of crown-like projections at the lorica edge as for adhesive disk. From L. tuba new species differs by considerably shorter stylotheca and prevalence to nematode host instead of echinoderms. PMID- 27395523 TI - A checklist of the leafhoppers of Iran (Hemiptera: Auchenorrhyncha:
Cicadellidae). AB - A list of Cicadellidae (leafhoppers) of Iran is provided based primarily on literature records from 1902 to the present. In total 390 species are recorded from 13 subfamilies. Ninety three of the recorded species are considered to be endemic to Iran. The current accepted name is given for each species together with synonyms and literature citations relating to Iran. Selenocephalus darei is recognized as a published misspelling for Selenocephalus dareicus Dlabola, 1981. There is no evidence that the Nearctic species Empoasca fabae (Harris, 1841) and Erythroneura comes (Say, 1825) have been found in Iran; previous records appear to have been based on misidentifications. A brief distribution of species within Iran is provided. PMID- 27395524 TI - A review of the New Caledonian Arpactophilus (Hymenoptera: Crabronidae). AB - The diverse and unique fauna of the apoid wasp genus Arpactophilus Smith (Pemphredoninae: Stigmini: Spilomenina) occurring in New Caledonia is reviewed. The previously documented diversity of 17 species is expanded to a total of 48, with 31 new species described and figured from across the main island. The new species proposed here are: Arpactophilus arha, A. arhoe, A. bwatoo, A. caac, A. cemuhi, A. drehu, A. drubea, A. fagauvea, A. futuna, A. fwai, A. haveke, A. iaai, A. jawe, A. kumak, A. merle, A. nemi, A. nengone, A. nere, A. numee, A. nyelayu, A. orowe, A. paici, A. pije, A. pwaamei, A. pwapwa, A. tayo, A. tiri, A. vamale, A. xaracuu, A. xaragure, and A. yuanga, spp. nov. Diagnoses are provided for those previously described species and a key to the fauna presented, although six species are considered of uncertain identity: A. arboreus Bohart, A. dolichocara Bohart, A. kraussi Bohart, A. nemoralis Bohart, A. nigripes Bohart, and A. sylvaticus Bohart. Brief comments are made regarding the unique species radiation occurring in New Caledonia and the potential for future discoveries in the systematics and biology of Australasian Arpactophilus. PMID- 27395525 TI - Taxonomic revision of the Neotropical pirate spiders of the genus Gelanor Thorell, 1869 (Araneae, Mimetidae) with the description of five new species. AB - We revise the Neotropical spider genus Gelanor Thorell, 1869 (Mimetidae). Gelanor is distributed from northeast Mexico to southern Uruguay , from sea level to 1,600 m. We describe five new species of Gelanor and report eleven new synonymies. Gelanor is here circumscribed to include ten species: Gelanor fortuna new species, Gelanor juruti new species, Gelanor moyobamba new species, Gelanor siquirres new species, Gelanor waorani new species, Gelanor altithorax Keyserling, 1893 (= Gelanor lanei Soares, 1941 new synonymy), Gelanor consequus O. P.-Cambridge, 1902 (= Gelanor depressus Chickering, 1956 new synonymy, Gelanor gertschi Chickering, 1947 new synonymy and Gelanor heraldicus Petrunkevitch, 1925 new synonymy), Gelanor innominatus Chamberlin, 1916, Gelanor latus (Keyserling, 1881) (= Gelanor mixtus O. P.-Cambridge, 1899 new synonymy, Gelanor mabelae Chickering, 1947 new synonymy, Gelanor ornatus Schenkel, 1953 new synonymy and Gelanor proximus Mello-Leitao, 1929 new synonymy) and Gelanor zonatus (C.L. Koch, 1845) (= Gelanor distinctus O-P. Cambridge, 1899 new synonymy, Gelanor insularis Mello-Leitao, 1929 new synonymy and Gelanor obscurus Mello-Leitao, 1929 new synonymy). In addition, we describe for the first time the males of G. altithorax and G. consequus. Species descriptions are provided for all ten species in the genus, together with a compilation of available data, including type specimens, type localities and morphological diagnoses. Light and electron microscope images and updated data on known geographical distributions, are also provided. We also discuss the phylogenetic placement of Gelanor in Mimetidae. PMID- 27395526 TI - The Geometrinae of Ethiopia II: Tribus Hemistolini, genus Prasinocyma
(Lepidoptera: Geometridae, Geometrinae). AB - In this paper we present a checklist and integrative revision for the genus Prasinocyma (Geometridae, Geometrinae, Hemistolini). With this contribution the checklist for the genus Prasinocyma in Ethiopia increases from eight to 40 species. Nineteen species and five subspecies are described as new for the science: Prasinocyma pedicata aethiopica subsp. n., Prasinocyma angolica pseudopedicata subsp. n., Prasinocyma bongaensis sp. n., Prasinocyma getachewi sp. n., Prasinocyma baumgaertneri sp. n., Prasinocyma robusta sp. n., Prasinocyma shoa yabellensis subsp. n., Prasinocyma amharensis sp. n., Prasinocyma magica sp. n., Prasinocyma batesi distans subsp. n., Prasinocyma monikae sp. n., Prasinocyma fusca sp. n., Prasinocyma leveneorum sp. n., Prasinocyma aquamarina sp. n., Prasinocyma beryllaria sp. n., Prasinocyma lutulenta sp. n., Prasinocyma septentrionalis sp. n., Prasinocyma fallax sp. n., Prasinocyma trematerrai sp. n., Prasinocyma trematerrai simienensis subsp. n., Prasinocyma angulifera sp. n., Prasinocyma stefani sp. n., Prasinocyma gemmifera sp. n., Prasinocyma discipuncta sp. n. Prasinocyma thiaucourti Herbulot, 1993 is downgraded from species rank to subspecies of P. immaculata (Thunberg, 1784) (stat. n.). Prasinocyma unipuncta Warren, 1897 is downgraded from species rank to synonymy of P. immaculata (Thunberg, 1784) (syn. n.). Prasinocyma nereis Townsend, 1952 (comb.n.) is transferred from genus Eretmopus to Prasinocyma. Thalassodes camerunalta Herbulot, 1986 (comb.n.) is transferred from genus Thalassodes to Prasinocyma. Thalassodini (syn.n.) are downgraded to synonymy of Hemistolini, here. PMID- 27395527 TI - Updated checklist of Iranian Opiinae (Hymenoptera: Braconidae). AB - An updated checklist of Opiinae from Iran is provided including 101 species from 11 genera (Atormus van Achterberg, 1997, Biosteres Foerster, 1862, Eurytenes Forster, 1862, Fopius Wharton, 1987, Indiopius Fischer, 1966, Opius Wesmael, 1835, Phaedrotoma Forster, 1862, Pokomandya Fischer, 1959, Psyttalia Walker, 1860, Utetes Forster, 1862 and Xynobius Forster, 1862) belonging to two tribes (Biosterini and Opiini). Moreover, seven species Biosteres (Chilotrichia) punctiscuta (Thomson, 1895), Biosteres (Biosteres) remigii Fischer, 1971, Eurytenes (Eurytenes) abnormis (Wesmael, 1835), Opius (Hypocynodus) ponticus Fischer, 1958, Opius pygmaeator (Nees, 1811), Opius (Nosopoea) speciosus Fischer, 1959 and Phaedrotoma nitidulator (Nees, 1834) are recorded for the first time from Iran. PMID- 27395528 TI - Three new species of Kalcerrytus Galiano, 2000 from Brazil (Araneae: Salticidae). AB - Three new species of Kalcerrytus Galiano, 2000 from the state of Para in the Brazilian Amazon are described: K. amplexus sp. nov. from Parque Nacional da Serra do Pardo, Sao Felix do Xingu, K. filipi sp. nov. from Reserva Ecologica do Jari, Almeirim, and K. leonardi sp. nov. from Juruti. These increase up to 18 the described species within the genus. PMID- 27395529 TI - Antillopsyche sessilis, new genus and species, a new Psychidae
(Lepidoptera: Tineoidea) from Cuba with an unusual larval feeding behavior. AB - A new genus and species, Antillopsyche sessilis Nunez & Davis, of Psychidae are described from Cuba, West Indies. The new taxon shares certain features with some members of the subfamily Arrhenophaninae but more with the larvae and the fully winged adult females of other subfamilies of Psychidae. Antillopsyche has been assigned provisionally to the subfamily Typhoniinae based on these similarities. Several aspects of its larval biology are described, including the sessile larval cases and foraging behavior, both unique among the known Psychidae. An undescribed species of Dryadaula Meyrick, 1893 (Dryadaulidae) was found inhabiting the larval cases of A. sessilis, but their ecological relationships remain unclear. Other ecological data for Antillopsyche such as distribution, habitat, and parasitoids are also provided. PMID- 27395530 TI - New species, new combinations and synonymies of Neotropical Galerucini (Coleoptera, Chrysomelidae, Galerucinae). AB - New species of Neotropical Galerucini are described and illustrated: Caraguata onca sp. nov., from southern Brazil (Rio Grande do Sul) and northern Argentina (Chaco); and Yingaresca cabrerae sp. nov., from Argentina (Misiones). Galerucella transversicollis Jacoby, 1886 is integrated to Yingaresca Bechyne. Two species originally described in Ophraella Wilcox are also transferred to Yingaresca: Yingaresca limonensis (Bechyne, 1997) comb. nov. and Yingaresca magdalia (Bechyne, 1997) comb. nov. Metrogaleruca obscura paraensis (Bechyne & Bechyne, 1961) is considered a synonym of Metrogaleruca obscura (Degeer, 1775). PMID- 27395531 TI - A new species of Pachycara Zugmayer, 1911 (Teleostei: Zoarcidae) from deep-sea chemosynthetic environments in the Caribbean Sea. AB - The 28th species of the eelpout genus Pachycara Zugmayer, 1911, is described from specimens collected from an active hydrothermal vent field at a depth of about 2300 m at the Mid-Cayman Spreading Centre of the Caribbean Sea. A tentatively identified early juvenile is recorded at a methane seep at a depth of 1049 m near Tobago. The new species is distinguished from its congeners mainly by its few pectoral fin rays, low vertebral counts, single, mediolateral branch of the lateral line system and presence of scales on the nape and cheeks. PMID- 27395532 TI - Synonymy of Katianna coeruleocephala Handschin, 1920 (Collembola: Katiannidae) with Bourletiella viridescens (Bourletiellidae). AB - Katianna coeruleocephala was described by Handschin in 1920 from Poespo, Java. It was collected in December, 1896 by Dr. Zehntner with the collecting details given as rotten "Louv" (leaves?) from live orchard. Handschin (1920) labelled his figures of the species (p. 146) as Katianna coerulescephala but the first spelling of the species name (p. 145) has priority. Katianna coeruleocephala has never been recollected. The only mention of the species in the literature since 1920 has been by Suhardjono (1989) in a check list for Indonesia and Suhardjono (2012) who listed it as present on Java and provided the main characteristics of the genus Katianna Borner, 1923. She stated it was a "new" (translate as endemic?) species in Java with a preferred habitat in cold and damp litter but no comment was made on the taxonomic status of the Indonesian species. PMID- 27395533 TI - Period of public commentary begins on the revised proposal of species-group level names, and on the proposal of genus-group level names of the Candidate Part of List of Available Names (LAN) in the phylum Rotifera. AB - Following ICZN (1999) Article 79 Chapter 17 http://www.nhm.ac.uk/hosted sites/iczn/code/), we, with the full support of the international community of rotifer researchers as expressed during subsequent international Rotifera symposia, developed a Candidate Part of the List of Available Names for species and genera of Rotifera from the start of zoological nomenclature to the year 2000. PMID- 27395534 TI - First description of the male of Yaobinthrips yangtzei (Thysanoptera: Thripidae). AB - The monobasic Thripinae genus Yaobinthrips has been known only from females, and the objective here is to provide a description of the male. A member of the Frankliniella genus-group, the type species, yangtzei Zhang et al. (2010) was described from specimens taken in Sichuan Province of Southwestern China from the flowers of Dalbergia yunnanensis [Fabaceae]. In April, 2015 a sample of both sexes of this thrips species was taken from the white flowers of the same plant species, but in Yunnan Province. This plant is actually widespread in southwestern China in Yunnan, Sichuan, Guizhou Provinces and Guangxi Zhuang Autonomous Region. Provinces, growing at an elevation ranging from 1400 to 2200 meters, and flowering from April to May (Li et al. 2007). PMID- 27395535 TI - Myostenostomum Bulbocaudatum (Catenulida, Stenostomidae): new for Ukraine, rare for the World. AB - At present, the stenostomid genus Myostenostomum Luther, 1960 according to Artois et al. (2013) contains 7 species: M. Bulbocaudatum Luther (type species), M. ilmenicum Rogozin, M. lutheri Rogozin, M. marcusi Rogozin, M. vanderlandi Rogozin, M. fasciatum (Veydovsky) and M. gigerium (Kepner & Carter), although the two latter are thought to belong to the genus Stenostomum Schmidt (Tyler et al. 2006-2015). A remarkable feature of the representatives of the genus Myostenostomum is a muscular ring on their gut. PMID- 27395536 TI - New data on caddisflies (Insecta: Trichoptera) from Lombok (Indonesia)
with descriptions of two new species. AB - Knowledge of caddisflies of the Sunda Islands was insufficiently known until recent times; a survey of the caddis fauna of this area was given by Malicky (2010) and some more data were published recently (Malicky et al. 2011). A summary on the particular features of Trichoptera from 3 adjacent islands, Bali, Lombok, and Java, were given by Malicky et al. 2014. These were the first surveys of the local caddisfly fauna of Lombok, listing 60 species and anticipating that more species should occur there. It was shown that the caddisfly fauna of these islands is largely homogenous and there are not sufficient differences between Bali and Lombok to support the hypothesis of Wallace's line (Malicky et al. 2014). The comparative analysis showed continuous impoverishment of the caddis fauna from the Asian continent over the chain of islands from west to east. Unfortunately, the Trichoptera fauna of the easternmost Sunda Islands, Sumba, Sumbawa, Flores, Timor, and the Moluccas is almost unstudied. The Trichoptera fauna of these islands is, according to present knowledge, Asian. Since the previous material from Lombok was collected only once at the end of the wet season, it was necessary to have more data from other seasons. Hence we made another effort to sample caddisflies in this area. As a result, 8 more species were found, 2 of which were new for science. The updated list (Table 1) includes now 68 species. PMID- 27395537 TI - Redescription of the Jamaican orb-weaving spider Chrysometa pecki Levi, 1986 (Araneae, Tetragnathidae), including the first description of the male. AB - The tetragnathid genus Chrysometa Simon, 1894 includes 138 species found in the Americas, ranging from the Caribbean to Chile (World Spider Catalog 2015). This genus was revised by Levi (1986), with more recent publications adding to the genus (Alvarez-Padilla 2007, Nogueira et al. 2011, Simo et al., in press). Following Alvarez-Padilla & Hormiga (2011), Chrysometa is differentially diagnosed from other American tetragnathids based on the male palp with a cymbial ectobasal process, cymbial ectomedian process, and embolic basal process, and a paracymbium articulated with a membrane. The epigynum is flat, with fertilization ducts present. Both sexes have guanine crystals in their abdomen and femora lacking trichobothria. Three Jamaican Chrysometa are known: C. pecki Levi, 1986, C. fuscolimbata (Archer, 1958) and C. linguiformis (Franganillo, 1930); all of them known from females only (Levi 1986). PMID- 27395538 TI - G. J. Billberg's (1833) 'On the ichthyology, and description of some new fish species of the pipefish genus Syngnathus'. AB - Gustaf Johan Billberg's review of ichthyology, published in Swedish in 1833 in the Linneska samfundets handlingar, mentions 92 fish taxa at genus and species level, 41 of which represent new taxa, unnecessary replacement names, or unjustified emendations. Billberg presents his own classification of fishes, in which five new family names are introduced: Ballistidae, Diodontidae, Ooididae, Chironectidae, and Macrorhyncidae. Diodontidae has priority over Diodontidae Bonaparte, 1835. Macrorhyncidae was published earlier than Gempylidae Gill, 1862, but the latter has priority by prevailing usage. Billberg mentions 61 genera of fishes, 41 of them listed only by name. Six generic names proposed by Billberg are available as unjustified emendations: Myxinus, Petromyzus, Scylia, Mustellus, Zyganna, and Ballistes. Brachionus is an unnecessary replacement name. Aphrus, Capriscus, Exormizus, Enneophthalmus, and Oedaus are nomina nuda. Eight new genera of fishes are proposed: Anodon, Posthias, Orbis, Sphaeroides, and Ooides are junior synonyms; Cotilla is a nomen oblitum in relation to Sufflamen Jordan, 1916; Tropigaster a nomen oblitum in relation to Aracana Gray, 1835; and Tetragonizus a nomen oblitum in relation to Lactoria Jordan & Fowler, 1902. Billberg lists 31 species of fishes. Three represent new combinations; two are nomina nuda. The following 14 new species are described based on literature: Raja forskohlii, Cephaloptera dumerillii, Myliobatis lacepedei, Scylia russelii, Anodon macropterus, Cotilla frenata, Monacanthus blochii, M. sebae, M. cuvieri, M. marcgravii, Tetraodon striatus, Orbis psittacinus, Orbis punctulatus, and Orbis guttatus. All of those are invalid, except Scylia russelii, which is a species inquirenda. The following nine species group names are unnecessary replacement names and consequently invalid: Raja arabica, Myliobatis rissoi, Scylia isabellina, Anodon cirrhosus, Anodon cornutus, Zyganna voracissima, Centrina broussonetii, Acipenser vulgaris, and Acipenser ichthyocolla. Three species of pipefishes of the family Syngnathidae are described and figured by Billberg from drawings of specimens observed on the Swedish West Coast. Syngnathus virens and S. pustulatus are junior synonyms of S. typhle Linnaeus, 1758. Syngnathus palmstruchii is a junior synonym of Entelurus aequoreus (Linnaeus, 1758). PMID- 27395539 TI - Two new species of Parastenocarididae (Copepoda, Harpacticoida) from India. AB - To date, 20 species of Parastenocarididae are known from the Indian subcontinent. This paper gives the description of two more new species from the coastal deltaic belt of the Rivers Krishna and Godavari in the Andhra Pradesh state of the southeastern Indian peninsula. They are: Parastenocaris enckelli n. sp. from a hyporheic habitat, and Dussartstenocaris bisetosa n. sp. from a farm bore. Parastenocaris enckelli belongs to the brevipes-group of the genus Parastenocaris Kessler, 1913 sensu Lang 1948 and Reid 1995, and is characterized by the following features: the male leg 4 basal complex consists of a large chitinized plate, with two digitiform hyaline structures at its proximal outer corner of the anterior surface, and one smooth, moderately strong, claw-like spine at the inner distal corner of basis; the endopod of the same leg is membranous, with bulbous proximal part having a diagonal row of three spinules, and its distal part is drawn out into smooth pointed structure; and the male leg 3 ancestral proximal segment is subproximally dilated, elongate, with ladle-shaped apophysis, which is slightly longer than the spiniform thumb. Parastenocaris enckelli is closely related to the Indian P. edakkal Totakura, Ranga Reddy & Shaik, 2014, and the Sri Lankan P. brincki Enckell, 1970. To accommodate Dussartstenocaris bisetosa in the monotypic Western Australian genus Dussartstenocaris Karanovic & Cooper, 2011, three of the original generic criteria are amended. D. bisetosa is chiefly characterized by the complex exopodal thumb on the male leg 3, the caudal ramus having only two lateral setae located slightly anterior to its midlength together with the distally inserted dorsal seta, and also the presence of a short spiniform process at the inner distal corner of leg 5 in both sexes. Dussartstenocaris bisetosa differs from D. idioxenos Karanovic & Cooper, 2011, by its shorter caudal rami, distinctly ornamented anal somite, two long modified spinules on the male leg 4 coxa, and rather small fifth legs with only two setae each in both sexes and smooth inner margins. This is the first report of the genus Dussartstenocaris from the Indian subcontinent. Brief biogeographic notes are also given for the two new species. PMID- 27395540 TI - Arctocypris fuhrmanni, n. gen., n. sp. (Crustacea, Ostracoda, Eucypridinae) from Spitsbergen (Norway). AB - Material from Spitsbergen (Norway) collected by Spitzenberger (1996) was reinvestigated. A new genus Arctocypris and a new species Arctocypris. fuhrmanni n. gen. n. sp. are described in the present paper. A key to the genera of the subfamily Eucypridinae is provided. At the moment Arctocypris n. gen. comprises four species: Arctocypris arctica (Olofsson, 1918) comb. nov.; A. dulcifons (Diebel & Pietrzeniuk, 1969) comb. nov.; A. foveata (Delorme, 1968) comb. nov. and Arctocypris fuhrmanni n. gen., n. sp. PMID- 27395541 TI - A taxonomic report on the cockroach genus Haplosymploce Hanitsch from China including one new species (Blattodea: Ectobiidae: Blattellinae). AB - The cockroach genus Haplosymploce Hanitsch is recorded from China for the first time with two species: H. andamanica (Princis, 1951) from Yunnan which was originally recorded from Andaman, and H. aurantiaca sp. n. from Hainan, a phototactic species remarkable by the orangish yellow cerci, it is very likely to be a wood-feeding species and thus, along with the genus, stands out among Ectobiidae (=Blattellidae). Male of both and female of H. aurantiaca sp. n. are described, illustrated and photographed; the female genitalia of the new species show a high degree of asymmetry. Photos of H. aurantiaca sp. n. in the wild are provided, as well as a key to the males of 8 out of 11 known species worldwide. PMID- 27395542 TI - The correct name for Oxyurichthys longicauda Steindachner and a few other errors. AB - In 2015, Pezold and Larson published a revision of the gobiid genus Oxyurichthys, and made an error in their use of the name O. uronema (Weber) for one of the species. The reasons for this would make a fine example of one of Evenhuis' taxonomic impediments to nirvana (2007). Pezold and Larson first considered collaborating on this work in 1983, but this did not happen until nearly a decade later. Intensive work began in 1996; by then Larson had examined syntypes of both species in 1988 and determined that Gobius uronema Weber, 1909, was the same species as Gobius longicauda Steindachner, 1893. PMID- 27395543 TI - First records of Lithodes longispina Sakai, 1971 (Crustacea: Decapoda: Anomura: Lithodidae) from southwestern Taiwan, including a site in the vicinity of a cold seep. AB - Lithodid crabs (Lithodidae Samouelle, 1819), commonly known as king crabs, are frequent targets of commercial fishing worldwide with most of them living in deep water (Sakai 1971; Ahyong et al. 2010). Lithodes Latreille, 1806, is the second largest genus of lithodid crabs, currently including 29 species worldwide (Ahyong 2010). In Taiwanese waters, however, only two species, L. turritus Ortmann, 1892, and L. formosae Ahyong & Chan, 2010, have been reported (Wu et al. 1998; Ahyong & Chan 2010; Ahyong et al. 2010). We report herein the discovery of L. longispina Sakai, 1971, previously known reliably only from Japan (Sakai 1971; Ikeda 1998; Ahyong 2010), from off southwestern Taiwan, including a specimen collected in the vicinity of a cold seep. PMID- 27395544 TI - Two new species of the genus Turbicellepora Ryland, 1963 (Bryozoa: Celleporidae) found on Lophelia coral from the Greenland slope. AB - The genus Turbicellepora was established by Ryland (1963) in the course of his work on the Norwegian bryozoan fauna. At present, the genus includes 71 recent and fossil species, which have been reported from all continents and seas (Bock & Gordon 2014). The distinctive characteristics of the genus include a multiporous ooecium, proximal orificial sinus, an asymmetrically placed peristomial avicularium and enlarged or vicarious avicularia (Ryland 1963). Occasionally, an additional pre-oral avicularium is also present (Hayward 1978). Colonies have a changeable form. They can be massive and branching or have the form of a mound or flat crust. The most comprehensive comparative study of European species of the genus, with detailed descriptions of 13 taxa, was carried out by Hayward (1978), who noted that the genus seemed to be centred in the Atlanto-Mediterranean region. PMID- 27395545 TI - New deep ocean Iravadiidae of the genus Ceratia (Caenogastropoda: Truncatelloidea) from an underwater canyon and adjacent regions of
the southwestern Atlantic (northeastern Brazil). AB - Previous studies on the mollusks from Brazilian underwater canyons have addressed the record and description of new species of aplacophorans, bivalves, scaphopods and/or gastropods (Leal & Simone 2000; Absalao 2010; Correa et al. 2014). Leal & Simone (2000) described a new bathyal gastropod of the family Pseudococculinidae collected from the continental slope and Doce River Canyon (960 m) off the state of Espirito Santo (southeastern Brazil). Absalao (2010) reported a number of species of gastropods, bivalves and scaphopods from Campos Basin off the state of Rio de Janeiro (southeastern Brazil). It is likely that some of these species reported by Absalao (2010) were collected from underwater canyons in the northern portion of the Campos Basin. Correa et al. (2014) recorded two species of aplacophorans of the genus Falcidens Salvini-Plawen, 1968 obtained from the continental slope and underwater canyons of Campos Basin. Certainly more species of mollusks were studied from Brazilian underwater canyons, but not duly mentioned in publications (i.e., the region of canyons may have been referred to as the continental slope or deep sea). PMID- 27395546 TI - Two new species of the subgenus Acanthohelea of Stilobezzia from Brazilian Amazonia (Diptera: Ceratopogonidae). AB - The predaceous genus Stilobezzia Kieffer is a large, diverse group of Ceratopogonidae that is worldwide in distribution except for Antarctica and some islands (Borkent 2014). Adult females are important predators on other small insects, and the immature stages are found in a wide variety of aquatic and semiaquatic habitats, including streams, lakes and pond margins, puddles, swamps, rice fields, rock pools, and tree holes (de Meillon and Wirth 1991; Cazorla et al. 2006). PMID- 27395547 TI - Helicopsis persica n. sp. from northern Iran (Gastropoda: Geomitridae). AB - Helicopsis Fitzinger, 1833 is a mainly eastern European genus of the xerophilous Helicellinae (Geomitridae, Helicoidea; for family systematics see Razkin et al. 2015) that is characterized by two symmetrical dart and accessory sacs. This is probably the plesiomorphous character state within the Geomitridae and Hygromiidae. Therefore, the delimitation and relationships of Helicopsis remained questionable (Hausdorf 1996). Most Helicopsis species are characterized by a lateral attachment of the outer layer of the penial papilla at the penis wall so that a cavity is separated in the proximal part of the penis (Schileyko 1978; Giusti et al. 1992; Hausdorf 1996). However, a similar cavity is present in some other Helicellinae (e.g., Pseudoxerophila, Xerolenta, Xeromunda). Giusti et al. (1992) considered these cavities artefacts, but it cannot be excluded that they are actually homologous to the cavity of Helicopsis. Therefore, it is doubtful whether such a cavity can be considered as an autapomorphy of Helicopsis. About ten species of Helicopsis are spread from Turkey and Bulgaria to the Ukraine with a centre of diversity on the Crimean peninsula. Only the type species, Helicopsis striata (Muller, 1774) is more widespread from Alsace in the west, the island Oland in the Baltic Sea in the north to Bulgaria and Turkey in the south and western Russia in the east. Furthermore, species from Morocco, Greece, Cyprus, Iran and the Kopetdag were classified as Helicopsis. The relationships between these species have to be examined in more detail. Here we describe a new Helicopsis species from Iran. PMID- 27395548 TI - Observations on the biology of Afrotropical Hesperiidae (Lepidoptera). Part 9. Hesperiinae incertae sedis: Zingiberales feeders, genera of unknown biology and an overview of the Hesperiinae incertae sedis. AB - The Afrotropical genera that have been recorded to feed on Zingiberales are documented. Partial life histories are presented for Erionota torus Evans (a South-East Asian species established in Mauritius), Semalea arela (Mabille), S. pulvina (Plotz), Xanthodisca vibius (Hewitson), X. rega (Mabille), Hypoleucis ophiusa (Hewitson), Caenides dacena (Hewitson), Osmodes adon (Mabille), Gretna cylinda (Hewitson) and Moltena fiara (Butler). Additional notes from the literature are provided on the genera Leona and Rhabdomantis. Notes on natural enemies of E. torus and M. fiara are included. We find that the Zingiberaceae and Costaceae feeding genera, Semalea, Xanthodiscus, Hypoleucis and Caenides (part) are united by a C-shaped raised rim to the prothoracic spiracle of the pupa. The pupa of Osmodes adon indicates this genus may have no close affinities to other Afrotropical genera for which the life history is known. The pupa of G. cylinda is unlike any other that we have documented and may reflect that this is the only species which we have found to be formed on the open leaf under surface rather than in a shelter. The early stages of M. fiara indicate affinities with Zophopetes and related genera. The paper concludes with a brief comparative discussion of the early stages of the Afrotropical Hesperiinae incertae sedis as a whole. There appear to be useful characters to group species by the ova and pupae but less so by the caterpillars. Based on pupae alone, the Hesperiinae incertae sedis might be divided into nine groups. PMID- 27395549 TI - Acailandica and Ipamerica: two new Neotropical grapholitine genera (Lepidoptera: Tortricidae). AB - Two genera, Acailandica and Ipamerica, and five species (Acailandica acailandiae, A. maja, A. hilara, A. cacaulandiae, Ipamerica auctuncus) are described as new. Species of Acailandica are brightly colored (= telochromatic), whereas those of Ipamerica are cryptic. Carpocapsa comptana Walker, Grapholitha subtilana Zeller, and Laspeyresia pyrozona Meyrick are transferred to Acailandica, resulting in the following new combinations: Acailandica comptana (Walker), A. subtilana (Zeller), and A. pyrozona (Meyrick). PMID- 27395550 TI - Eriophyoid mites (Acari: Prostigmata: Eriophyoidea) from Turkey: description of five new species. AB - Five new eriophyoid mite species (Eriophyidae) from Turkey are described and illustrated in this paper: Aceria vanensis n. sp., Aceria onosmae n. sp., Aculus lydii n. sp., Aculus gebeliae n. sp. and Aculus spectabilis n. sp.. The descriptions are based on the morphology of females collected from weedy plants, respectively: Amaranthus retroflexus L. (Amaranthaceae), Onosma isauricum Boiss. et Heldr. (Boraginaceae), Hypericum lydium Boiss. (Hypericaceae), Lotus gebelia Vent. (Fabaceae) and Stachys spectabilis Choisy ex DC. (Lamiaceae). The new species were found to be vagrant on their host plants with no visible damage symptoms observed. PMID- 27395551 TI - Generic delimitation between Fragariocoptes and Sierraphytoptus (Acari: Eriophyoidea: Phytoptidae) and a supplementary description of Fragariocoptes gansuensis with remarks on searching for mummified eriophyoid mites in herbaria under UV light. AB - Generic concepts of Fragariocoptes Roivainen, 1951 and Sierraphytoptus Keifer, 1939 are discussed and the correct delimitation between these two genera is given. A supplementary description of Fragariocoptes gansuensis Wei, Chen & Luo, 2005 is included based on fresh specimens from Astrakhan, Russia and dried mummies found in old herbaria collected in 1919 from southern European Russia of the cinquefoil, Potentilla bifurca L. (Rosaceae) with pathological stem proliferation. The male of this species is described for the first time. The cuticle of eriophyoid mummies emitted a faint glow under UV light wavelength equal to 365 nm of a common UV Light-Emitting diode (LED) lamp showing that this characteristic could be useful for quickly detecting eriophyoids in old herbaria which would otherwise be almost indistinguishable against the background under the regular white light source of a stereomicroscope. This was only possible for plant material stored in appropriate conditions enabling the autofluorescent signal of the dried mite cuticle to remain strong enough for observation. PMID- 27395552 TI - Descriptions of two new notodontid species from the relic Fagus forests in northeastern Taiwan (Lepidoptera, Notodontidae). AB - Two new Fagus-feeding notodontids, i.e. Syntypistis taipingshanensis Wu & Hsu sp. n. and Pheosiopsis seni Wu & Hsu sp. n. are recently discovered from the relic Fagus forests in northeastern Taiwan. Based on the genitalia structures, the closely relatives of two new species are S. melana Wu & Fang, 2003 and P. albalienata Kishida & Kobayashi, 2005, respectively, both occurring in the Fagus forests of Southern China. PMID- 27395553 TI - A new species of Speleogobius (Teleostei: Gobiidae) from the Western Mediterraenean Sea. AB - A new goby species, Speleogobius llorisi sp. nov. (Teleostei: Gobiidae) is described from the circalittoral sea bed at 46-69 m depth off the Balearic Islands, western Mediterranean. Six specimens, four females and two males, of the new species were collected from beam trawl samples carried out on the red algae beds off the south west coast of Mallorca Island. Among others, the main traits that differentiate the new species from the only congeneric species, S. trigloides, are the presence of preopercular head canal with pores gamma, delta, epsilon vs. preopercular head canal absent; a longer snout, equal or longer than eye vs. shorter than eye; lower lip ending anteriorly slightly in front of upper lip vs. upper lip slightly protruding lower lip; scales in lateral series 28 or 29 vs. 26; scales in transverse series 6 vs.7-8. It also differs from S. trigloides in some non-overlapping morphometrics and in coloration. All individuals of the new species were collected from Peyssonnelia beds, beds of red algae dominated by species of the family Peyssonneliaceae. The generic diagnosis of Speleogobius is revised. PMID- 27395554 TI - Neothalassius, a new genus of Parathalassiinae (Diptera: Dolichopodidae s.lat.) from the Pacific coast of South America. AB - A new genus, Neothalassius gen. nov., and two new species, Neothalassius triton sp. nov. and Neothalassius villosus sp. nov., are described from rocky shorelines along the Pacific seacoast of South America. The phylogenetic placement of Neothalassius within the subfamily Parathalassiinae is discussed. PMID- 27395555 TI - A new species of eriophyoid mite (Acari: Eriophyoidea) on Rosa sp. from Israel. AB - A new species of eriophyoid mite from a hybrid of Rosa sp. (Rosaceae) found in Israel is described and illustrated. Eriophyes eremus n. sp. is a refuge-seeking type mite, inhabiting flower buds and petiole bases, causing no apparent damage to the host plant. Eighteen eriophyoid species are known to inhabit Rosa sp. and those are listed here along with type localities, damage they cause and host plant details. PMID- 27395556 TI - A new species of Microhyla (Anura: Microhylidae) from Sri Lanka: an integrative taxonomic approach. AB - Species boundaries of Microhyla rubra of India and Sri Lanka were assessed using the following criteria: genetic barcoding, morphology, and vocalization. We use a ca. 500 bp fragment of the 16S rRNA mitochondrial gene and show that there is an uncorrected pairwise distance of 2.7-3.2% between the Indian and Sri Lankan populations of M. rubra. We show that they are different in several call characteristics such as, dominant frequency, call duration, call rise time and pulse rate. Morphologically, the Sri Lankan population can be distinguished from the typical M. rubra described from southern India, by a combination of characters: body size, skin texture, and feet dimensions. We recognize the population from Sri Lanka as a new species, Microhyla mihintalei sp. nov., a widely distributed lowland species with an elevational distribution of up to 500 m a.s.l. PMID- 27395557 TI - On the genus Paralobella (Collembola: Neanuridae: Lobellini) with description of a new Chinese species. AB - Remarks on the genus Paralobella Cassagnau & Deharveng, 1984 and a key to world species is provided. P. breviseta sp. nov. is described from Eastern China, it is distinguished from all known members of the genus by its biggest size, digitate body dorsolateral and lateral tubercles and very short setae on dorso-internal tubercles. PMID- 27395558 TI - Optical coherence tomography images of three different overlapping stents. PMID- 27395559 TI - Finally, a continuous national multicenter registry: Primary angioplasty in Portugal. PMID- 27395560 TI - Pulmonary varix: A case report. AB - The authors report a case of multiple pulmonary varices, a rare disease characterized by aneurysmatic venous dilatations, which can be present at any age and without gender predominance, occurring in isolation or associated with obstruction of the pulmonary veins. This condition usually manifests as a lung mass with variable clinical consequences. PMID- 27395561 TI - Telerheumatology: A technology appropriate for virtually all. AB - BACKGROUND/PURPOSE: Telerheumatology services were developed at Dartmouth Hitchcock Medical Center (DHMC) to bring specialty care to New Hampshire (NH) and Vermont (VT) where a large proportion of the population lives in rural areas (60%) with limited resources and access to care. We sought to learn what challenges and accomplishments our early telemedicine program has encountered since inception. METHODS: As part of a quality improvement initiative we performed an IRB-exempt retrospective review of patients seen in the telerheumatology clinic at DHMC from October 2011 to December 2014. We also interviewed the participants; including providers, presenters, and patients regarding their experience of care. We assessed both patient and provider satisfaction with the experience. RESULTS: Between October 2011 and December 2014, 176 patients were seen via telerheumatology between two clinical sites over the course of 244 telerheumatology patient visits. The top diagnosis for patients during the telerheumatology visits was inflammatory arthritis (n = 156, 63.9%). We found 19% of patients to be inappropriate for the visit type for the following two main reasons: the underlying diagnosis was unclear or the disease was too complex. CONCLUSION: The use of telerheumatology has successfully increased access to specialty care in rural regions of NH and VT with good patient and provider satisfaction. While telerheumatology improved the access to specialty care, consideration should be given to selecting the appropriate patient for this visit type given that 19% of patients were deemed inappropriate. We propose a triage mechanism to ensure that patients are appropriately paired to the proper visit type in the future. PMID- 27395562 TI - Pelvic packing after peripartum hysterectomy: some concerns and additions. PMID- 27395564 TI - The contribution of the polio eradication initiative to narrowing the gaps in the health workforce in the African Region. AB - INTRODUCTION: The Global Polio Eradication Initiative (GPEI) massively invested to overcome the crippling disease in countries of the WHO African Region. In the context of economic crisis, almost all countries in the Region lack an adequate health workforce. Large amounts were invested by GPEI in human resources. This paper shows how the human resources funded by polio contributed to narrowing the gaps in health workforce and helped strengthening and supporting other priority health programmes in Angola, Chad, DRC, Nigeria, Tanzania, and Togo. METHODS: The health workforce strengthening methods used in the five different countries included the following: policy development and strategic planning, microplanning, capacity building of public health and community workers, implementation and services, monitoring and evaluation, advocacy and social mobilization, and programme review. RESULTS: Staff funded by polio helped with achieving good coverage in vitamin A and insecticide-treated mosquito nets (Angola, Chad); improvement of EPI and integrated disease surveillance indicators, improved quality of data (all five countries), administrative support, smooth introduction of new vaccines, increased case detection, and early isolation of patients suffering from the Guinea worm (Chad); reduction of cholera, extension of directly observed TB short course treatment (Democratic Republic of Congo); significant staff performance improvement (Nigeria). DISCUSSION: GPEI investment achieved far beyond its primary goal, and contributed to narrowing the gaps in the health workforce in countries of the African Region, as demonstrated by the best practice documentation exercise. We recommend that expertise and experience of polio funded staff should be leveraged to strengthen, expand and support other public health programmes. PMID- 27395563 TI - Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment. AB - The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viral and other microbial pathogens in their genome (so called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens. The rVSV/HIV-1 vaccine vector was attenuated by combining two major genome modifications. These modifications acted synergistically to greatly enhance vector attenuation and the resulting rVSV vector demonstrated safety in sensitive mouse and non-human primate neurovirulence models. This vector expressing HIV-1 gag protein has completed evaluation in two Phase I clinical trials. In one trial the rVSV/HIV-1 vector was administered in a homologous two dose regimen, and in a second trial with pDNA in a heterologous prime boost regimen. No serious adverse events were reported nor was vector detected in blood, urine or saliva post vaccination in either trial. Gag specific immune responses were induced in both trials with highest frequency T cell responses detected in the prime boost regimen. The rVSV/HIV-1 vector also demonstrated safety in an ongoing Phase I trial in HIV-1 positive participants. Additionally, clinical trial material has been produced with the rVSV vector expressing HIV-1 env, and Phase I clinical evaluation will initiate in the beginning of 2016. In this paper, we use a standardized template describing key characteristics of the novel rVSV vaccine vectors, in comparison to wild type VSV. The template facilitates scientific discourse among key stakeholders by increasing transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. PMID- 27395565 TI - Protection induced by a commercial bivalent vaccine against Foot-and-Mouth Disease 2010 field virus from Ecuador. AB - Foot-and-Mouth Disease serotype O circulated endemically in Ecuador for many years, with an upsurge occurring in 2009. This manuscript describes retrospectively in vitro and in vivo laboratory studies to predict the field effectiveness of a commercial FMD vaccine to protect against the field strain, and explains the key actions and epidemiological strategies followed by the country to control the disease. The results established that the use of a good quality oil vaccine, manufactured with strains that were isolated long ago: O1 Campos Br/58 and A24 Cruzeiro Br/55; combined with the correct epidemiological strategies, are useful to control field strains when used in periodic biannual vaccination campaigns. PMID- 27395566 TI - Antibody persistence after serogroup C meningococcal conjugate vaccine in children with sickle cell disease. AB - BACKGROUND: A decline of protective antibody titers after MCC vaccine has been demonstrated in healthy children, this may be an issue of concern for risk groups. The aim of this study was to evaluate the persistence of bactericidal antibodies after MCC vaccine in sickle cell disease (SCD) patients. The type of vaccine used and booster response were also analyzed. METHODS: SCD patients (n=141) previously immunized with MCC vaccines had blood drawn 2-8 years after the last priming dose. They were distributed according to age at primary immunization into groups: <2 years and 2-13 years and evaluated by years since vaccination (2-3, 4-5 and 6-8). Serum bactericidal antibodies with baby rabbit complement (rSBA) and serogroup C-specific IgG concentrations were measured. The correlate of protection was rSBA titer ?8. Subjects with rSBA <8 received a booster dose and antibody levels re-evaluated after 4-6 weeks. RESULTS: For children primed under 2years of age rSBA titer ?8 was demonstrated in 53.3%, 21.7% and 35.0%, 2-3, 4-5, 6-8years, respectively, after vaccination, compared with 70.0%, 45.0% and 53.5%, respectively, for individuals primed at ages 2 13years. rSBA median titers and IgG median levels were higher in the older group. Six to eight years after vaccination the percentage of patients with rSBA titers ?8 was significantly higher in the group primed with MCC-TT (78.5%) compared with those primed with MCC-CRM197 [Menjugate(r) (33.3%) or Meningitec(r) (35.7%)] (p=0.033). After a booster, 98% achieved rSBA titer ?8. CONCLUSION: Immunity to meningococcal serogroup C in SCD children declines rapidly after vaccination and is dependent on the age at priming. Booster doses are needed to maintain protection in SCD patients. Persistence of antibodies seems to be longer in individuals primed with MCC-TT vaccine comparing to those immunized with MCC CRM197. PMID- 27395568 TI - Helminth parasites of Australasian monotremes and marsupials. AB - This work includes all published records, to April 2015, of the helminths occurring in Australasian monotremes and marsupials, with due regard for synonymy and an attempt to include life history studies, pathological observations and epidemiology. It also contains all unpublished records known to us and referrable, by accession numbers, to curated collections in Australia and overseas. Information is presented by host family, genus, species, sub-species or chromosome race and includes the names of all host species from which no parasites have been recorded. Most records pertain to free-living and wild animals; where they do not, they have been annotated appropriately. Unpublished information known to the authors has been included in annotations to entries, where appropriate. Parasites are arranged as follows: Trematoda, Cestoda, Nematoda, Acanthocephala, and their systematic position is indicated by abbreviations placed before the name. The authority for each parasite record is given after the author's name, as a number in parentheses, and this refers to the numbered (1-664) list of references. A parasite-host list is presented alphabetically, irrespective of taxonomic affiliation together with the host species in which they are known to occur. Hosts are arranged initially by family and alphabetically within each family. PMID- 27395567 TI - Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models. AB - BACKGROUND: Extra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method. METHODS: Three doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2MUg or 20MUg per O-antigen, subcutaneously), mice (0.2MUg or 2MUg per O-antigen, subcutaneously) and rats (0.4MUg or 4MUg per O antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4MUg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16MUg total polysaccharide, intramuscularly). Serum IgG and IgM antibodies were measured by ELISA. RESULTS: Robust antigen-specific IgG responses were observed in all animal models, with increased responses in rabbits when administered with adjuvant. O antigen specific antibody responses persisted up to 168days post-priming. Booster immunization induced a rapid recall response. Toxicity of ExPEC-4V when administered to rats was considered to be at the no observed adverse effect level. CONCLUSIONS: ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation. PMID- 27395569 TI - Crickets (Insecta, Orthoptera, Grylloidea) from Southern New Caledonia,
with descriptions of new taxa. AB - Intensive sampling of cricket communities has been undertaken in southern New Caledonia in selected plots of vegetation, i.e. rain forest, preforest and maquis shrubland. This leads to the discovery of many new taxa, which are described in the present paper, together with closely related species from nearby areas. Descriptions are based on general morphology and characters of genitalia. Calling songs are described for all acoustic taxa but two, and observations about species habitats are given. In total, 35 species belonging to 13 genera are studied, including 21 new species and two new genera. The pattern of assemblages of cricket species in New Caledonia is discussed. PMID- 27395570 TI - The South Temperate Pronophilina (Lepidoptera: Nymphalidae: Satyrinae): a phylogenetic hypothesis, redescriptions and revisionary notes. AB - Phylogenetic analysis of the south-temperate members of Pronophilina (Nymphalidae: Satyrinae) using mitochondrial and nuclear gene data corroborated monophyly of the clade and provided a framework for its systematic revision based on morphology. Of the 19 genera, 8 have been synonymized with 16 new combinations: Cosmosatyrus stelligera n. comb., C. dubii n. comb., Neomaenas tristis n. comb., Neosatyrus boisduvalii n. comb., N. humilis n. comb., N. schajovskoii n. comb., N. vesagus n. comb., Punargentus chiliensis n. comb., P. lamna cuzcoensis n. comb., P. monticolens n. comb., P. tandilensis n. comb., Pampasatyrus edmondsii n. comb., P. gustavi n. comb., Tetraphlebia eleates n. comb.,T. leucoglene n. comb., and T. patagonica n. comb. Neomaenas poliozona eustephanos nom. nov., stat. nov. has been raised to a valid subspecies. Neomaenas monachus limonias and Pampasatyrus gustavi penai have been demoted to subspecies and Auca nycteropus and A. pales have been synonymized with A. coctei. The phylogenetic placement of Neomaniola euripides, not formally revised here, is discussed. PMID- 27395571 TI - Notes on the genus Conocephalus (Orthoptera: Tettigoniidae; Conocephalinae; Conocephalini) from India and description of two new species. AB - The present paper describes two new species of Conocephalus: Conocephalus decaspinosus sp. nov. and C. kwasiphaiensis sp. nov., as additions to the previously known species of the genus; among these, two species have been reported for the first time from India, viz., C. concolor peneri and C. vaginalis. The key morphological characters of the head, pronotum, cerci, spines on the fore tibiae, hind femora, stridulatory file and the ovipositor have been illustrated with suitable line drawings to distinguish the reported new species. The distribution map of the species in India has been provided with a key to the subgenera. PMID- 27395572 TI - The Ambrysus Stal (Heteroptera: Naucoridae: Cryphocricinae) of Mexico:
Revision of the subgenus Syncollus La Rivers. AB - The subgenus Ambrysus (Syncollus) La Rivers is mostly Neotropical and includes nine described species. Features uniting species in this subgenus are related to the position of the propleura with respect to the prosternum in males and females, as well as characteristics of tergum V and the genitalia of males. Three species of Syncollus are known from Mexico including Ambrysus baeus Polhemus & Polhemus, A. circumcinctus Montandon, and A. pygmaeus La Rivers. The remaining six species in the subgenus are distributed in Central and South America. Herein we review Syncollus and revise the Mexican fauna. More specifically, three new species from Mexico are described: A. chiapanecus n. sp., A. totonacus n. sp., and A. xico n. sp. The subspecies A. circumcinctus caliginosus Usinger, A. c. concavus La Rivers, and A. c. extremus La Rivers are proposed as junior synonyms of A. c. circumcinctus Montandon. Ambrysus partridgei De Carlo is transferred from Syncollus to the subgenus Ambrysus. PMID- 27395573 TI - New diagnosis for species of Plutomurus Yosii (Collembola, Tomoceridae), with descriptions of two new species from Georgian caves. AB - Two new species of the genus Plutomurus, P. revazi sp. nov. from Prometheus and Satsurblia caves and P. eristoi sp. nov. from Satevzia Cave are described, illustrated and differentiated from other morphologically closely related species. A high variability in the number of teeth in the claw, unguiculus and mucro of P. revazi sp. nov. demonstrate that these characters are not useful for species diagnosis. However, dorsal chaetotaxy was shown to be stable character for this purpose. Analysis of DNA sequences for the COI and 28S genes is congruent with species-level groups delimited by chaetotaxy, and provide additional support for chaetotaxy as the most reliable morphological character system to distinguish species in Plutomurus. A key to species of the genus Plutomurus found in Georgia is provided, which for the first time includes characters of the macrochaetotaxy. PMID- 27395574 TI - Paroctonchus nanjiensis gen. nov., sp. nov. (Nematoda, Enoplida, Oncholaimidae) from intertidal sediments in the East China Sea. AB - Paroctonchus nanjiensis gen. nov., sp. nov. is described from a sand beach in the China Nanji Islands Natural Reserve in the East China Sea. Paroctonchus nanjiensis is distinct in the family Oncholaimidae in having more than three teeth, a character found otherwise only in the monotypic genera Octonchus and Patagonema. The new genus and species differs from Octonchus and Patagonema in the number and pattern of teeth, bearing three large teeth with the left ventrosublateral one the largest plus about 27 small teeth distributed on the wall of buccal cavity. By contrast, Octonchus possesses one large tooth plus eight small teeth, while Patagonema has three large teeth with the right ventrosublateral one the largest plus 12 small teeth on three mandibular ridges. Moreover, Paroctonchus nanjiensis differs from Octonchus also in position of the amphidial aperture (located in the middle portion of buccal cavity vs. at the base of buccal cavity), and from Patagonema in the absence of a demanian system (vs. present) and the presence of two subventral rows of wart-like precloacal supplements (vs. a ventral row of papillate supplements). We provide an improved diagnosis for the subfamily Octonchinae, and discuss the evolution of teeth in the family Oncholaimidae. PMID- 27395575 TI - Review of the genus Stigmaporus S. Zonstein, 2001 (Hymenoptera: Pompilidae), with description of new species. AB - The genus Stigmaporus S. Zonstein, 2001 is newly recorded from Russia. Four species are reviewed. Stigmaporus volgadon Loktionov & Lelej, sp. nov. from South of European part of Russia (Volgograd Prov. and Astrakhan Prov.) is described and illustrated. Stigmaporus centralasiaticus Wolf, 1990 is distributed in Xinjiang (China) not in Afghanistan, Pakistan or former USSR as was recorded earlier. Key to species is provided. PMID- 27395576 TI - Amnestus mendeli sp. n., the first burrower bug species (Hemiptera: Heteroptera: Cydnidae) recorded on Ascension Island, central Atlantic Ocean. AB - A new species of the genus Amnestus Dallas, 1851, Amnestus mendeli, is described from the cloud zone of Green Mountain, Ascension Island, and compared with its closest relatives, the Brazilian Amnestus lenkoi Froeschner, 1975 and Amnestus pequinus Froeschner, 1975. It is the first representative of the family Cydnidae recorded on the island thus far. The species is presumed to be an introduction from the Americas, but the hypothesis that it might be endemic to Ascension Island is also not excluded. PMID- 27395577 TI - Taxonomic status of a population of Gymoncypris waddelli Regan, 1905 (Cypriniformes: Schizothoracinae) distributed in Pengqu River, Tibet, China. AB - Gymnocypris waddelli, a highland cold-water fish, is distributed among rivers and lakes of the southern Qinghai-Tibet Plateau. Although previously described as G. waddelli, specimens from the Pengqu River are morphologically distinguishable from those from Lake Yamzhog Yumco, which is the type locality of G. waddelli. We investigated morphological variations of G. waddelli specimens from Pengqu River and Lake Yamzhog Yumco using not only traditional morphological methods but also newly-developed geometric morphometric analysis; furthermore, mitochondrial Cytochrome b (Cyt b) gene analysis was employed to explore the phylogenetic position of the Pengqu River population. Our morphological analyses suggested that G. waddelli from the Pengqu River had an obtuse snout, nearly straight oral fissure, shorter lower jaw than upper jaw, broad mouth and sparse inside gill rakers of the first arch relative to the Lake Yamzhog Yumco population. The strongly supported monophyly of Pengqu population according to mitochondrial datasets was obtained, indicating genetic differences between Pengqu River and Lake Yamzhog Yumco populations. Given their substantial genetic and morphological divergence, specimens from Pengqu River warrant recognition as a distinct species, here described and named Gymnocypris pengquensis. PMID- 27395578 TI - The type species of the genus Geotrygon Gosse, 1847 (Aves: Columbidae). AB - The generic name Geotrygon was introduced by Gosse (1847: 316) for some doves from the island of Jamaica and has been subsequently used for the so-called quail doves of Middle and South America (Baptista et al. 1997; Gibbs et al. 2001; Dickinson 2003; Dickinson & Remsen 2013). Johnson & Weckstein (2011) and Banks et al. (2013) indicated that this genus is polyphyletic. The application of a generic name is determined by its type species (Art. 42.3 of the International Code of Zoological Nomenclature; ICZN 1999; hereafter the Code). A literature search showed that different nominal species have been proposed as the type species of Geotrygon, and the situation thus requires clarification. PMID- 27395579 TI - First record of the sicklefin devilray Mobula tarapacana (Myliobatiformes: Mobulidae) from Australian waters. AB - The sicklefin devilray Mobula tarapacana (Philippi, 1892) is one of the largest and least known mobulids (Compagno & Last 1999; Couturier et al. 2012). Collections, fisheries bycatch data and visual records suggest it is primarily oceanic, with a circumglobal tropical and warm temperate distribution (Notarbartolo-di-Sciara 1987; Compagno & Last 1999; Gadig & Sampaio 2002; White et al. 2006a, b; Weir et al. 2012; Sobral 2013; Tomita et al. 2013). In the Pacific Ocean it has been recorded from Chile, Gulf of California, Japan, Taiwan, South China Sea and Indonesia (Compagno & Last 1999; White et al. 2006b; Couturier et al. 2012; Tomita et al. 2013). PMID- 27395580 TI - Morphological clarifications of Australian hylid and limnodynastid tadpoles. AB - Tadpole morphology usually is consistent within taxa and ecologies (Altig & Johnston 1989), but the occurrences of unique morphologies offer informative perspectives on the potential diversity of these structures. Anstis (2013) characterized most of the tadpoles of Australia, but a thorough understanding of certain morphological features requires closer examinations. Until we understand the morphological features of anuran larvae, and preferably their ontogeny, we cannot productively discuss their evolution or ecological significance. PMID- 27395581 TI - A review of Adelphocoris-Creontiades-Megacoelum complex (Hemiptera: Heteroptera: Miridae: Mirini), with descriptions of two new genera and four new species. AB - The Adelphocoris-Creontiades-Megacoelum complex of genera is reviewed. Diagnostic characters for each included genus and species are provided. Two new genera, Poppiomegacoelum n. gen. and Pseudomegacoelum n. gen., are proposed to accommodate Poppiomegacoelum gearyi n. sp. from Australia and four species from west Palearctic previously classified under Megacoelum Fieber, 1858 respectively. Three new species from Australia, Papua New Guinea and Solomon Islands are described: Adelphocorisella rubricornis n. sp., Waucoris solomonensis n. sp. and Waucoris tricolor n. sp. The following new combinations are made: Adelphocorisella brunnescens (Poppius, 1915) [for Adelphocoris brunnescens Poppius, 1915], A. relatum (Distant, 1904) [for Megacoelum relatum Distant, 1904], Macrolygus rubrus (Carvalho, 1987) [for Waucoris rubrus Carvalho, 1987], Miyamotoa mussooriensis (Distant, 1909) [for Megacoelum mussooriense Distant, 1909], Orientomiris ater (Poppius, 1915) [for Creontiades ater Poppius, 1915], O. brunneus (Poppius, 1914) [for Creontiades brunneus Poppius, 1914], O. furhstorferi (Poppius, 1915) [for C. furhstorferi Poppius, 1915], O. maculicollis (Poppius, 1915) [for C. maculicollis Poppius, 1915], O. marginatus (Poppius, 1915) [for C. marginatus Poppius, 1915], O. montanus (Poppius, 1915) [for C. montanus Poppius, 1915], O. monticola (Poppius, 1914) [for Megacoelum monticola Poppius, 1914], O. orientalis (Poppius, 1915) [for Creontiades orientalis Poppius, 1915], O. pallidicornis (Poppius, 1915) [for Megacoelum pallidicorne Poppius, 1915], O. ravana (Kirkaldy, 1909) [for Kangra ravana Kirkaldy, 1909], O. sumatranus (Poppius, 1915) [for Adelphocoris sumatranus Poppius, 1915], O. uzeli (Poppius, 1910) [for Creontiades uzeli Poppius, 1910), Poppiocapsidea tagalica (Poppius, 1915) [for Megacoelum tagalicum Poppius, 1915], Pseudomegacoelum angustum (Wagner, 1965) [for Megacoelum angustum Wagner, 1965], P. beckeri (Fieber, 1870) [for M. beckeri (Fieber, 1870)], P. irbilanum (Linnavuori, 1988) [for M. irbilanum Linnavuori, 1988], P. quercicola (Linnavuori, 1965) [for M. quercicola Linnavuori, 1965], Waucoris poppiusi Cherot & Malipatil [new name and new combination for Megacoelum papuanum Poppius, 1915]. The following new synonymies are established: Creontiades vittipennis Reuter, 1905 (valid name) = Creontiades vitticollis Poppius, 1915 (new subjective synonym), Poppiocapsidea biseratensis (Distant, 1903) (valid name) = Megacoelum townsvillensis Distant, 1904 (new subjective synonym). Cheilocapsidea insignis (Distant, 1909) is recorded from Laos and the male genitalic structures are briefly described for the first time. A lectotype is designated for Capsus antennatus Kirby, 1891, Creontiades ater Poppius, 1915, Creontiades brunneus Poppius, 1914, Creontiades fruhstorferi Poppius, 1915, Creontiades marginatus Poppius, 1915, Creontiades uzeli Poppius, 1910, Megacoelum mussooriensis Distant, 1909, Megacoelum relatum Distant, 1904, and Megacoelum townsvillensis Distant, 1904 (original combinations). A key for the genera included in the Adelphocoris-Creontiades Megacoelum complex is given. PMID- 27395582 TI - Hexactinellida (Porifera) from the Drake Passage (Southern Ocean) with a description of three new species. AB - The Drake Passage has over 20 seamounts and ridges but it is notorious for large waves, fierce storms and strong currents that make benthic sampling difficult and therefore infrequent. Seamounts often have diverse sponge communities and may have high levels of endemism. Hexactinellida from Sars Seamount, an area in which the sponges had not previously been studied, and the Shackleton fracture zone were collected on a research cruise by the Nathaniel B Palmer in the Drake Passage, Southern Ocean. In total, from all cruise stations, 103 specimens of Hexactinellida were collected, however many appeared to be fragments of dead specimens and could not be identified due to missing microscleres. From Sars Seamount 127 sponge specimens were taken and from the Shackleton Fracture Zone 76 sponge specimens were taken; of these 36 and 16 respectively were Hexactinellida. From these two areas three new species of Hexactinellida are described: Doconesthes robinsoni sp. nov., Sympagella walleri sp. nov. and Caulophacus palmeri sp. nov and new records were made of Aulocalyx irregularis and Rossella antarctica. PMID- 27395583 TI - Revision of genus Texoreddellia Wygodzinsky, 1973 (Hexapoda, Zygentoma, Nicoletiidae), a prominent element of the cave-adapted fauna of Texas. AB - While many cave-adapted organisms tend to be endemic to single locations or restricted to single karstic regions, the troglobitic silverfish insects of genus Texoreddellia can be found in scores of different cave localities that cover a range of nearly 160,000 km2. They are among the most important and common representatives of the cave-adapted fauna of Texas and Coahuila, in northern Mexico. Using morphological and mitochondrial gene sequence data, we have corroborated the presence of at least six different species within the genus and provided species identifications to populations inhabiting 153 different cave locations. Results show that species ranges are larger than previously reported and that ranges tend to greatly overlap with each other. We have also found that different species of Texoreddellia commonly inhabit the same cave in sympatry. Data supports that some species of Texoreddellia can easily disperse through the extensive network of cracks, fissures and smaller cavities near the surface and epikarst. PMID- 27395584 TI - Two new species of Megistophylla Burmeister (Coleoptera: Scarabaeidae: Melolonthinae) from Taiwan, with notes on the genus. AB - The genus Megistophylla (Coleoptera: Scarabaeidae: Melolonthinae) was first reported from Taiwan with the descriptions and illustrations of two new species, Megistophylla formosana Wang & Li, new species () and Megistophylla xitoui Li & Wang, new species (). An annotated checklist and modified key for the species in the genus are provided. The information in checklist for each species includes: literature review, synonymy, distribution, and type locality. PMID- 27395585 TI - New species of Zygoclistron Rehn, 1905 (Insecta: Orthoptera: Acrididae: Copiocerinae) in the central corridor of the Atlantic Forest biome. AB - Herein we describe a new species of Copiocerinae, Zygoclistron ruschii Silva n. sp., from Atlantic Forest remnants in southeastern Brazil, collected from the Reserva Biologica Augusto Ruschi in the Santa Teresa municipality, Espirito Santo state, Brazil. The diagnosis of this new species is based on phallic complex and terminalia characters. PMID- 27395586 TI - Eigenmannia besouro, a new species of the Eigenmannia trilineata species-group (Gymnotiformes: Sternopygidae) from the rio Sao Francisco basin, northeastern Brazil. AB - A new species of the Eigenmannia trilineata species-group is described from the rio Sao Francisco basin, Brazil. It is distinguished from closely related species by a unique set of characters, including a subterminal mouth, the presence of ii,13-14 pectoral-fin rays, a coronomeckelian bone that is 30% the length of Meckel's cartilage, the specific pattern of the dentition of the premaxilla and dentary, and the more anterior origin of the superior midlateral stripe. Comments on species of the E. trilineata species-group are presented. PMID- 27395587 TI - Neotype designation for Calotes versicolor Daudin, 1802 (Sauria: Agamidae) with notes on its systematics. AB - Calotes versicolor Daudin, 1802 is one of the most widespread agamid lizard species which was described without a locality. The type specimen of the species has long been considered lost; however most workers considered Pondicherry as the type locality for the species. Studies by Zug et al. 2006 confirmed that C. versicolor is a complex of multiple species which necessitates fixing type locality and specimen for the species in order to resolve the systematics of the species complex. An adult male from Pondicherry was collected and is here designated as the neotype. A re-description of the species is provided along with notes on systematics of the species. PMID- 27395588 TI - A new genus and species of Xyphosiini (Diptera: Tephritidae) from Iran. AB - Valera, a monotypic new genus (Tephritidae, Tephritinae, Xyphosiini) and Valera ariana n. sp., the type and only known species, are described from Iran. Systematic relationships with other Xyphosiini are discussed and a key to the genera of the tribe Xyphosiini is presented. PMID- 27395589 TI - Rhyzodiastes (Temoana) xii sp. nov. (Coleoptera: Rhysodidae: Clinidiini),
a new species from Hainan Island, China. AB - Rhyzodiastes (Temoana) xii sp. nov. (Coleoptera: Rhysodidae: Clinidiini) is described from Hainan Island, China. Important morphological characters of the new species are illustrated. An updated key to nine species of of the R. (T.) singularis species-group is compiled so as to include the new species. PMID- 27395590 TI - Garra longchuanensis, a new cyprinid (Teleostei: Cypriniformes) from southern China. AB - A new species of the genus Garra is described from the Longchuan Jiang River, a tributary flowing to the Yiluowadi Jiang (Irrawaddy River) basin in Tengchong, Yunnan, South China. Garra longchuanensis is distinct from other Chinese congeners, except for G. qiaojiensis, in having 12 circumpeduncular scales, a well-developed rostral lobe with irregular distributed acanthoid tubercles, a deep groove to form a transverse lobe and a conspicuous, heavily tuberculated quadrate proboscis, and from G. qiaojiensis in having a slightly pointed snout (vs. rounded), a long and slender caudal peduncle (length 17.8-20.6% SL vs. 15.5 17.1%, width 10.9-12.6% SL vs. 11.3-12.6%), pectoral fin with 15-16 (vs. 13) branched rays, pelvic fin with 9 (vs. 8) branched rays, and an anterior position of anus (anus to anal distance 27.2-39.1% of pelvic to anal distance vs. 22.8 28.3%). PMID- 27395591 TI - A review of the genus Gyrophaena Mannerheim 1830 (Coleoptera: Staphylinidae: Aleocharinae: Gyrophaenina) of the Caucasus and adjacent territories. AB - A review of the genus Gyrophaena Mannerheim 1830 of the Caucasus and adjacent territories, with faunistic data for twenty three species is provided. G. (Phaenogyra) atropatena Enushchenko, sp. nov. of Azerbaijan and Iran is described and illustrated. One new synonymy is established: G. (s.str.) caucasica A. Strand 1939 = G. (s.str.) cultellata Assing 2009, syn. nov. G. (s.str.) orientalis A. Strand 1938 and G. (s.str.) poweri Crotch 1867 are reported for Caucasus for the first time. Records of G. (s.str.) congrua Erichson 1837, G. (s.str.) joyioides Wusthoff 1937, and G. (s.str.) pulchella Heer 1839 for Caucasus are not confirmed by new material. G. (s.str.) caucasica is recorded for the Republic of Crimea and Rostov Area of Russia for the first time. Additional new Palaearctic records for some species are provided. An illustrated key for all studied species of Caucasus is given. PMID- 27395592 TI - Description of new endemic species of the genus Niphargus Schiodte, 1849 (Amphipoda: Niphargidae) from a karst spring in Zagros Mountains in Iran. AB - New species of the genus Niphargus is described and named as N. kermanshahi sp. nov. from a karst spring in west of Iran. This species is identified based on the analysis of morphological characters and 28S ribosomal DNA sequences. Taxonomic status and phylogenetic position of this species is discussed in comparison to other Iranian species of Niphargus genus. PMID- 27395593 TI - Corvoheteromeyenia Ezcurra de Drago, 1979 (Spongillidae, Porifera): Genus review with proposal of neotype of Corvoheteromeyenia heterosclera (Ezcurra de Drago, 1974). AB - Corvoheteromeyenia Ezcurra de Drago, 1979 (Spongillidae) is endemic to the Neotropical Region and was erected to comprise C. australis (Bonetto & Ezcurra de Drago, 1966) and C. heterosclera (Ezcurra de Drago, 1974). However, the distinction between these species was not well-established and the type materials were not deposited in the collections as otherwise indicated in the original descriptions. Thus, in order to elucidate their specific status, this paper provides a review of the genus and proposes a neotype designation of Corvoheteromeyenia heterosclera, following Article 75 of the International Code for Zoological Nomenclature (ICZN 1999). A total of 41 specimens were analyzed and identified as belonging to Corvoheteromeyenia. Based on the literature and additional specimens, the redescription of C. australis and C. heterosclera is presented. The acanthoxea microscleres were stated as the distinctive character of both, but are present only in C. heterosclera. Corvoheteromeyenia sanidastosclera Pinheiro, Silva & Calheira, 2015, is distinct from congeners by the presence of sanidaster gemmuloscleres and also differ from C. heterosclera by the absence of acanthoxea microscleres. A key to species of Corvoheteromeyenia is provided. PMID- 27395594 TI - The coastal marine Tardigrada of the Americas. AB - The Western Hemisphere or the New World, also known as the Americas (North, Central and South America, associated islands and included seas) have historically been divided into two Realms, the Nearctic and Neotropical based on terrestrial biogeography. The coasts of these two terrestrial realms are bordered by six marine realms, 14 marine provinces and 67 marine ecoregions. From current literature, a comprehensive list of the marine tardigrade fauna from the Americas is presented. Data on marine tardigrades were obtained from 385 published Records of the Occurrence (RoO) of a species, their location, tidal zone, and the substrates from which they were reported. Authors' identifications were accepted at face value unless subsequently amended. Thirty genera and 82 species or subspecies are reported from the Americas; 49 species are documented from margins of the terrestrial Nearctic realm (North America) and 48 from terrestrial Neotropical realm (South America) with only 17 species occurring in both. We define cosmopolitan distribution for marine tardigrades as occurring in or on the margins of five of the seven oceans, only two species of marine tardigrade meets this standard. From the Americas 39 species have been described as new to science, 32 species appear restricted to the hemisphere. Taxa were assigned to marine ecoregions based on adjacent geopolitical units (country, states, provinces, etc.) described in published records. Although tardigrades have been reported from all six marine realms, they are only known from 21 of the 67 ecoregions. Most marine tardigrade sampling in the Americas has focused on near shore substrate (sand, mud, barnacles); for some species no substrates have been reported. The west coasts of both continents have little or no data about tardigrade presence. PMID- 27395595 TI - Three new species of Myrsidea (Phthiraptera: Menoponidae) from New Zealand passerines (Aves: Passeriformes). AB - Myrsidea ivanliteraki new species, M. novaeseelandiae new species, and M. hihi new species are described and illustrated from New Zealand birds, with Gymnorhina tibicen, Anthornis melanura and Notiomystis cincta as type hosts respectively. Also, Myrsidea vincula is redescribed and illustrated from one sample ex Strepera fuliginosa from Australia. Keys for the identification of females and males of the five species of Myrsidea recorded from New Zealand are also given. PMID- 27395596 TI - Mesobiotus philippinicus sp. nov., the first limnoterrestrial tardigrade from the Philippines. AB - The limnoterrestrial tardigrade fauna of the Philippines is completely unknown. In this paper, we describe the first ever limnoterrestrial water bear species from this southeast Asian country, Mesobiotus philippinicus sp. nov., found in a moss sample collected in Quezon City. Apart from morphometrics and imaging in light microscopy, we also analysed the new species under scanning electron microscope and sequenced four DNA markers differing in mutation rates, three nuclear (18S rRNA, 28S rRNA, and ITS-2) and one mitochondrial (COI). This allowed not only a detailed description but also provided barcodes to aid future species identification. The new species belongs to the harmsworthi group and is most similar to M. diffusus (Binda & Pilato, 1987), M. pseudocoronatus (Pilato et al., 2006), M. montanus (Murray, 1910) and M. mottai (Binda & Pilato, 1994), but differs from these species by whorled egg processes and dimensions of some morphometric traits. The 28S rRNA, ITS-2 and COI sequences presented in this paper are the first published DNA sequences for the genus Mesobiotus. PMID- 27395597 TI - Sympotthastia wuyiensis sp. n. from China, with description of the immature stages of S. takatensis (Tokunaga) (Diptera, Chironomidae). AB - Sympotthastia wuyiensis sp. n. is described and illustrated as male imago from China. The immature stages of S. takatensis (Tokunaga) are described. The generic diagnosis is emended. Key to the known adult males, larvae and pupae of the genus worldwide is presented. PMID- 27395598 TI - A new species of the genus Xenylla Tullberg, 1869 (Collembola: Hypogastruridae) from Korea, with a key for East Asian species. AB - A new species of Hypogastruridae from Korea, Xenylla namia sp. nov., is described and illustrated. The new species is easily distinguished from previously described Xenylla species by a combination of the following characters: labral setae arrangement of 2/5,5,4, labial papilla E with one guard seta (e3), head without c2 seta, thoracic sterna II and III with a pair of medial setae, abdominal sternum III with 1 median seta above the retinaculum, abdominal sternum IV with seta m1. An identification key to East Asian species of Xenylla with detailed differences between East Asian Xenylla species is provided. PMID- 27395599 TI - Sinostoma yunnanicum, the first nemastomatine harvestman in China (Arachnida: Opiliones: Nemastomatidae). AB - The easternmost Nemastomatinae species, Sinostoma yunnanicum n. gen., n. sp., from northern Yunnan, China is described. It extends the geographic distribution of Nemastomatinae by roughly 3000 km southeastwards. Within Nemastomatinae Sinostoma displays plesiomorphic characters, including the long, basic bulb of the truncus shaft and the extremely short glans of penis, armed with short robust spines. Sinostoma may represent a relict line in the early evolution of nemastomatine harvestmen. PMID- 27395600 TI - Revision of the water-holding frogs, Cyclorana platycephala (Anura: Hylidae), from arid Australia, including a description of a new species. AB - The water-holding frog, Cyclorana platycephala, occurs in the Australian arid and semi-arid zones but not in the central Australian deserts. Recent inspection of morphological variation in adults and larvae suggests that the taxon comprises three regional populations: eastern, northern and western that may each represent separate species. To assess the systematic status of these populations, we documented phylogenetic relationships using mitochondrial and nuclear DNA markers, divergence in adult and larval morphology and male advertisement call. Our molecular genetic data demonstrates that the western population of C. platycephala is not the sister taxon of eastern and northern representatives of this nominate species, as the latter two are more closely related to another morphologically distinct species, C. verrucosa. Discriminant Function Analysis of 14 morphological traits in adults and 15 in larvae showed a high degree of morphological differentiation of western versus eastern/northern C. platycephala. Calls of eastern and western populations differed in duration, pulse rate, frequency and especially in amplitude modulation pattern across the call duration. We describe the western population as a new species, whose range is contained entirely within Western Australia. In addition, we redescribe Cyclorana platycephala, quantify morphological and genetic differences between the eastern and northern populations, and conclude that these data support recognition of a single species, Cyclorana platycephala, for populations found in New South Wales, the Barkly Tablelands and south-eastern Northern Territory, Queensland and South Australia. PMID- 27395601 TI - The Eastern Arc Mountains and coastal forests of East Africa-an archive to understand large-scale biogeographical patterns: Pseudotomias, a new genus of African Pseudophyllinae (Orthoptera: Tettigoniidae). AB - A new genus of Pseudophyllinae restricted to East Africa is described. Data on the ecology, and the habitat are provided. The biogeographical pattern and morphology suggests an old radiation since Tomias from Central and West Africa is the closest relative to Pseudotomias. The old forests of East Africa could hereby be the source of representatives of this old radiation since venation is less reduced in East African taxa of Phyllomimini. PMID- 27395602 TI - A new side-neck turtle (Pelomedusoides: Bothremydidae) from the Early Paleocene (Danian) Maria Farinha Formation, Paraiba Basin, Brazil. AB - Limestone and marl from Maria Farinha Formation (Paraiba Basin, NE Brazil) accumulated in a shallow continental shelf environment during the expansion of the Atlantic Ocean in early Paleocene (Danian). It contains a rich paleontological record, which comprises many marine invertebrates, several species of bony and cartilaginous fishes, a crocodyliform and turtle remains. Here, we describe a new genus and species of pleurodire turtle from Maria Farinha Formation, based on a nearly complete plastron, an incomplete left pelvic girdle, and four dermal plates of the carapace. We tested the phylogenetic position of Inaechelys pernambucensis gen. et sp. nov. by including it in a comprehensive cladistic analysis of pleurodires. The new species is included within Botrhemydidae, with affinities to Bothremydini, positioned as sister group of Rosasia soutoi. Inaechelys pernambucensis gen. et sp. nov. differs from R. soutoi for the almost straight anterior lobe cranial edge of its plastron, as well as for its pentagonal shaped entoplastron and its abdominal shield midline, which is considerably smaller than the respective femoral shield midline. Inaechelys pernambucensis is the first turtle species formally described from Brazilian Paleocene strata. Within Bothremydidae, it is also the first conclusively fully marine species described for this country. This new record contributes to the understanding of the ecology and paleobiogeographical distribution of Bothremydidae family. PMID- 27395603 TI - A taxonomic study on the species of the genus Diestramima Storozhenko (Orthoptera: Rhaphidophoridae; Aemodogryllinae). AB - A taxonomic study of the genus Diestramima Storozhenko, 1990 is presented. Eleven new species are described: D. excavata sp. nov., D. parabispinosa sp. nov., D. tibetensis sp. nov., D. guangxiensis sp. nov., D. subrectis sp. nov., D. curvicaudata sp. nov., D. beybienkoi sp. nov., D. triangulata sp. nov., D. brevis sp. nov., D. emeiensis sp. nov., D. conica sp. nov.. A key to the species of Diestramima is given. PMID- 27395604 TI - The Alucitidae (Lepidoptera) of Malawi with descriptions of five new species. AB - An overview of Alucitidae species from Malawi is presented, with 20 species reported. Five of them are described as new for science: Alucita nyasa Ustjuzhanin & Kovtunovich sp. nov., Alucita aarviki Ustjuzhanin & Kovtunovich sp. nov., Alucita malawica Ustjuzhanin & Kovtunovich sp. nov., Alucita murphy Ustjuzhanin & Kovtunovich sp. nov. and Alucita sochivkoi Ustjuzhanin & Kovtunovich sp. nov. Four new synonyms are established. The following species are considered synonyms of Alucita seychellensis (T.B.Fletcher, 1910): Alucita granata (Meyrick, 1921) syn. nov., and Alucita imbrifera (Meyrick, 1929) syn. nov. Alucita myriodesma (Meyrick, 1929) is considered a junior synonym of Alucita ectomesa (Hering, 1917) syn. nov., and Alucita isodina (Meyrick, 1920) a synonym of Alucita spicifera (Meyrick, 1911) syn. nov. All the Alucitidae species are reported for the Malawian fauna for the first time. PMID- 27395605 TI - On Brazilian Helobata Bergroth, 1888 (Coleoptera: Hydrophilidae): description of two new species, new records, and key to species. AB - Two new species of Helobata Bergroth, 1888 (Hydrophilidae: Acidocerinae) from Brazil are described and illustrated. Helobata amazonensis sp. nov. is described based on an adult male specimen from the Amazon River floodplains, Amazonas State. Helobata pantaneira sp. nov. is described based on an adult male specimen collected from swamps in the Pantanal biome, in Mato Grosso State. Helobata corumbaensis Fernandez & Bachmann, 1987, H. larvalis (Horn, 1873) and H. quatipuru Fernandez & Bachmann, 1987 are recorded for the first time from Mato Grosso; Amazonas, Ceara and Mato Grosso; and Rio de Janeiro States respectively. Diagnosis, illustrations, a checklist and a key to Brazilian species of Helobata are provided. PMID- 27395606 TI - Description of a new genus and two new species of high frequency cicada from New Caledonia (Insecta: Hemiptera, Cicadoidea, Cicadidae). AB - The new genus Murmurillana Delorme gen. nov., is described within the tribe Cicadettini Buckton, 1889, designating Murmurillana inaudibilis Delorme sp. nov., as the type species. Murmurillana inaudibilis Delorme sp. nov. and Murmurillana paenetacita Delorme sp. nov. are described from New Caledonia. They are respectively found in mid altitude dense Niaouli shrub (Melaleuca quinquenervia, Myrtaceae) vegetation, mixed with dense fern cover (Pteridium sp., Dennstaedtiaceae) on the Massif of Aoupinie (800 m) and on foothills of the Mont Panie (570 m). Male calling songs of the two new species are described from field recordings. These calling songs exhibit unusually high dominant frequencies. A key to the species of Murmurillana Delorme gen. nov., is also provided. PMID- 27395607 TI - Cyathoshiva amaleshi gen. n. sp. n. (Nematoda: Cyatholaimidae) from the coast of India. AB - A new genus, Cyathoshiva, of free-living marine nematodes from the subfamily Cyatholaiminae (family Cyatholaimidae, order Chromadorida), is described from the Indian coast. The new genus differs from other known Cyatholaiminae genera in having a unique combination of morphological characters: buccal cavity with well developed dorsal tooth and two subventral teeth, proximally unpaired gubernaculum and non-cup shaped supplements. The type species Cyathoshiva amaleshi gen. n. sp. n. is characterized by having multispiral amphids with 4.5 turns, punctated cuticle with a weak lateral differentiation, a conical tail, three supplements possessing both tubular and setoid parts, and a gubernaculum with a serrated and dentate distal end. PMID- 27395608 TI - Two species of the deep-water shrimp genus Nematocarcinus A. Milne-Edwards, 1881 (Crustacea, Decapoda, Caridea, Nematocarcinidae) from the Mexican Pacific. AB - The distribution of two species of the deep-water shrimp genus Nematocarcinus A. Milne-Edwards, 1881, occurring off the west coast of Mexico is analyzed based on a large series of recently collected material. Nematocarcinus faxoni Burukovsky, 2000, is by far the most common and abundant species in the area and it is distributed throughout the central and southern Gulf of California and off the entire Baja California Peninsula south to 17o10'15"N. Based on characteristics observed in the new samples and in the type material, N. agassizii Faxon, 1893, is reinstalled as a valid species, and no longer considered a junior of N. gracilipes A. Milne-Edwards, 1881, as proposed by Cardoso & Burukovsky (2014). Along the Pacific coast of Mexico, N. agassizii exhibits a more restricted distribution and it was collected only off the Baja California Peninsula. Previous records of this species in the Gulf of California, where N. faxoni was the only representative of the genus captured during this survey, are considered doubtful. PMID- 27395609 TI - MANOELA M. F. MARINHO & FRANCISCO LANGEANI (2016) Reconciling more than 150 years of taxonomic confusion: the true identity of Moenkhausia lepidura, with a key to the species of the M. lepidura group (Characiformes: Characidae). Zootaxa, 4107 (3): 338-352. PMID- 27395610 TI - Taxonomy of the genus Diochus Erichson, 1839 (Coleoptera: Staphylinidae, Staphylininae, Diochini) in China with descriptions of four new species. AB - This paper studies the taxonomy of the genus Diochus Erichson, 1839 (Coleoptera: Staphylinidae, Staphylininae, Diochini) from China. Four new species are described: Diochus bicornutus sp. nov. from Fujian, Hainan, Zhejiang, Guangxi and Yunnan, D. ampullaceus sp. nov. from Guangxi, D. bisegmentatus sp. nov. from Hainan and Yunnan, and D. membranaceus sp. nov. from Fujian. All other species previously reported from China are redescribed based on the examination of the holotypes, except the holotype of D. antennatus (Motschulsky, 1858), which was missing. Line drawings of the now missing holotype of D. antennatus (Motschulsky, 1858) are provided. A lectotype is designated for D. conicollis (Motschulsky, 1858). The Chinese fauna of the genus Diochus is now represented by eight species (four doubtfully recorded) and a key to all the Chinese species is provided. The type specimens of the new species are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZ-CAS). PMID- 27395611 TI - Five new species of Zercon C. L. Koch, 1836 (Acari: Zerconidae) from northwestern Turkey. AB - Mites belonging to the genus Zercon collected from the Thrace region in Turkey are investigated. Five new species, Z. filiformis sp. nov., Z. geliboluensis sp. nov., Z. sklarsimilis sp. nov., Z. tekirdagensis sp. nov. and Z. thracicus sp. nov., are described and illustrated. Zercon similifoveolatus Ivan & Calugar is newly recorded for the Turkish fauna. Female specimens of Z. sklari Balan are reported and descibed for the first time in Turkey. Some known zerconid mites are recorded from new localities. A key to species of the genus Zercon known from Turkey is included. PMID- 27395612 TI - New species of Cladiopsocus Roesler (Psocodea: 'Psocoptera': Psocomorpha: Cladiopsocidae) from the Colombian Amazonia. AB - Ten species of Cladiopsocus Roesler were identified among recent collections from the Colombian departments of Amazonas and Putumayo. Eight new species were found, five from Putumayo and three from Amazonas, that are here described and illustrated. C. ramulosus (Enderlein) and C. domesticus (New) were found in the Putumayo department. The number of species in the genus is increased to 28, with two from Angola, and 26 from the Neotropics. An identification key to the males of the neotropical species is included. PMID- 27395613 TI - Taxonomy and natural history of the myrmecophilous genus Clinterocera Motschulsky, 1858 (Coleoptera: Scarabaeidae: Cetoniinae) from China and adjacent regions: definition of species group and revision of the C. discipennis species group. AB - The Asian genus Clinterocera Motschulsky, 1858 (Coleoptera: Scarabaeidae: Cetoniinae: Cremastocheilini) is redescribed and divided into four species groups based on adult external characters. The definition of species groups and an identification key to these species groups are provided. The C. discipennis species group is revised, and two species are recognized: C. discipennis Fairmaire, 1889 and C. trimaculata Ma, 1993. Callynomes rufiventris Fairmaire, 1904, Callynomes rufithorax Moser, 1901, Callynomes cruciatus Moser, 1901, Callynomes vitalisi (Bourgoin, 1924), and Clinterocera rubra Ma, 1992 are placed as junior synonyms of Clinterocera discipennis. The male of Clinterocera trimaculata is described for the first time and newly recorded from Vietnam. Diagnoses and illustrations of Clinterocera discipennis and Clinterocera trimaculata are provided, with comments on the intraspecific variations. New distribution records of the two species are presented on a map. Brief natural history notes and host ant Liometopum sinense Wheeler, 1921 (Hymenoptera: Formicidae) record of Clinterocera trimaculata are also given. PMID- 27395614 TI - Palaearctic Hoplitis bees of the subgenera Formicapis and Tkalcua (Megachilidae, Osmiini): biology, taxonomy and key to species. AB - Formicapis and Tkalcua are related subgenera of the osmiine bee genus Hoplitis (Megachilidae) containing four and three species, respectively. H. (Formicapis) species inhabit open forests and windfalls mainly in the boreal zone with one species distributed across the Holarctic and three species occurring in eastern Asia. H. (Tkalcua) species live in deserts and semideserts from the Canary Island and northern Africa eastwards to the Arabian Peninsula. Analysis of female pollen loads, field observations and literature data reveal that H. (Formicapis) species have a distinct or even exclusive preference for the flowers of herbaceous Rosaceae as pollen hosts, while H. (Tkalcua) species appear to be pollen generalists. Nesting sites of H. (Formicapis) are insect burrows in dead wood, while the only H. (Tkalcua) species, whose nesting behaviour is known, builds its brood cells inside empty snail shells. Species of both subgenera construct brood cell partitions and nest plug with masticated leaves, which, however, are mixed with sand grains in H. (Tkalcua) zandeni (Teunissen & van Achterberg 1992). The taxonomic revision of H. (Formicapis) and H. (Tkalcua) revealed the existence of two undescribed species, H. (Formicapis) coreensis spec. nov. from South Korea and H. (Tkalcua) emiratensis spec. nov. from the United Arab Emirates. Hoplitis excisa (Morawitz 1880) is newly assigned to H. (Formicapis), whereas H. latifemoralis (Wu 1985), formerly considered to belong to H. (Formicapis), is removed from this subgenus due to morphological and biological differences and newly assigned to Hoplitis subgenus incertum. Identification keys for all H. (Formicapis) and H. (Tkalcua) species are given. PMID- 27395615 TI - Description of a new species of brooding spider crab in the genus Paranaxia Rathbun, 1924 (Brachyura: Majoidea), from northern Australia and Indonesia. AB - A new species, Paranaxia keesingi sp. nov., is described based on specimens collected in northern Australia. The new species differs from its only congener, P. serpulifera (Guerin, 1832, in Guerin-Meneville 1829-1837), by several characters including carapace setation, sternal cavities, absence of a subhepatic spine, presence of a sharp spine on the posterodistal angle of the cheliped merus, relatively shorter chelipeds, and longer and more slender ambulatory legs. Morphological separation of the two species is supported by 12s rDNA sequence divergences of 7.4-8.2%. Like P. serpulifera, the newly described species exhibits direct development with females carrying juvenile individuals under the pleon. Both species are sympatric, but Paranaxia keesingi sp. nov. is found in deeper waters than P. serpulifera. PMID- 27395616 TI - No longer supple? Molecular phylogeny suggests generic reassignment of Lygosoma ashwamedhi (Sharma, 1969) (Reptilia: Scincidae). AB - Morphometrics and phylogenetic analysis based on 12S and 16S ribosomal RNA (rRNA) gene sequences reveal that Riopa ashwamedhi Sharma, 1969 is placed incorrectly in the genus Riopa or Lygosoma, and we transfer this taxon to the genus Eutropis. New material of this rare and endemic species forms the basis of the generic reassignment. A detailed description of E. ashwamedhi (Sharma, 1969) comb. nov. and natural history notes are provided based on the new material collected in Andhra Pradesh, India. PMID- 27395617 TI - Narcine baliensis, a new species of electric ray from southeast Asia (Chondrichthyes: Torpediniformes). AB - A new species of numbfish, Narcine baliensis, sp. nov., is described from the tropical eastern Indian Ocean from Indonesia. It is superficially similar to N. brevilabiata and N. atzi in aspects of its color pattern, but is distinguished from both congeners in details of its color pattern, in tooth band morphology, and in proportions of its dorsal fins, among other features. Narcine baliensis, sp. nov., is unique in having a dorsal color pattern composed of large, circular, ovoid or elongate dark brown spots or blotches on dorsal disc along with more numerous small (about eye-sized or slightly greater) brownish, subcircular spots, with large blotches and small spots surrounded by a very slender creamy-white pattern, as well as in having broadly circular upper and lower tooth bands of about the same width and shape. The genus Narcine is now composed of 20 valid species, but uncertainty remains concerning the identification and morphological variation of some of its species in the tropical Indo-West Pacific region. PMID- 27395618 TI - Conflict resolution of grammar and gender for avian species-group names under Article 31.2.2 of the ICZN Code: is gender agreement worth it? AB - We analyze recent nomenclatural treatment of selected avian species-group names that may be either adjective and variable or noun and invariable. In 27 such names, we found that 14 previously identified as adjectives are nouns under Article 31.2.2 of the International Code of Zoological Nomenclature. Five of them may require correction in current checklists; they are bresilius in Ramphocelus bresilius (Linnaeus, 1766) to bresilia, germana in Amblyornis macgregoriae germana Rothschild, 1910 to germanus, argentinus in Muscisaxicola cinereus argentinus Hellmayr, 1932 to argentina, martinicus in Porphyrio martinicus (Linnaeus, 1766) to martinica, and moluccus in Threskiornis moluccus (Cuvier, 1829) to molucca. Mindful of the compounding effect of species-genus recombination from taxonomic revision, we reach the conclusion, not new, that the requirement for gender agreement in species-group names is the single biggest cause of nomenclatural instability in zoology. To resolve it, we support replacing gender agreement by original spellings for species-group names. PMID- 27395619 TI - Redescription of Alpheus vladivostokiensis (Vinogradov, 1950), a large and conspicuous snapping shrimp from the northern Sea of Japan (Decapoda: Caridea: Alpheidae). AB - The poorly described Alpheus vladivostokiensis (Vinogradov, 1950) comb. nov., originally assigned to the genus Betaeus Stimpson, 1860 and hitherto considered as a nomen dubium, is redescribed based on material recently collected in Troitza Bay in the Russian Far East and Hakodate Bay in southern Hokkaido, Japan, as well as older material deposited in the Zoological Museum of the Moscow State University. Since Vinogradov's material is considered as non-extant, a neotype of A. vladivostokiensis is designated. Alpheus vladivostokiensis is closely related to A. japonicus Miers, 1879, a species occurring in deeper waters of Japan, Korea, China and Taiwan. All previous records of A. japonicus from the Russian Far East are reassigned to A. vladivostokiensis. PMID- 27395620 TI - Leptalpheus pereirai sp. nov., a new alpheid shrimp from Panama and Venezuela (Decapoda: Caridea). AB - A new species of the infaunal alpheid shrimp genus Leptalpheus Williams, 1965 is described based on material from three localities on the Caribbean coast of Panama and Isla Chimana Grande, Venezuela. Leptalpheus pereirai sp. nov. belongs to a group of species characterised by the presence of well-developed adhesive disks on the major chela and appears to dwell in burrows of the large callianassid ghost shrimp, Glypturus acanthochirus Stimpson 1866. PMID- 27395621 TI - A review of the Japanese species of the choragella-group of the genus Morophaga Herrich-Schaffer (Lepidoptera: Tineidae), with description of a new species. AB - The taxonomy of the Japanese species of the choragella-group of the genus Morophaga is reviewed. Previously, one species, Morophaga fasciculata Robinson, 1986, was recorded from Japan. In the present study, a second species, Morophaga plana, sp. nov., is described based on adult morphological characters. PMID- 27395622 TI - A review of world Diallactiini (Diptera, Cecidomyiidae, Winnertziinae), with the description of six new genera and seventeen new species. AB - Fossil and extant Diallactiini, which are mycophagous Cecidomyiidae (gall midges), are reviewed globally for the first time. Johnsonomyia Felt, 1908 stat. rev. is restored from synonymy with Haplusia Karsch, 1877 (with Chastomera Skuse, 1888 confirmed as a junior synonym) and both genera are re-defined. Haplusia funebris Plakidas, 2007 and Wyattella lobata Yukawa, 1968 are newly combined in Johnsonomyia. Gynapteromyia Mamaev, 1965 is shown to be a species-rich, almost cosmopolitan genus, which absorbs several of the species previously classified in Haplusia or Chastomera. Gynapteromyia brevipalpis (Mamaev, 1964) comb. nov., G. heteroptera (Mamaev & Spungis, 1980) comb. nov., G. hondrui (Mamaev, 1964) comb. nov., G. indica (Grover, 1971) comb. nov., G. longipalpis (Mamaev, 1964) comb. nov., and G. stricta (Fedotova & Sidorenko, 2005) comb. nov. are all new combinations. ?Palaeocolpodia eocenica Meunier, 1904 is considered to be a nomen dubium. Prior to the present study, the tribe Diallactiini contained 28 extant species classified in 6 genera. Previously unworked specimens of Diallactiini gathered by the author in the past 15 years were examined and identified as belonging to 57 different species, all unnamed. From that material, the following new taxa are described: Bruneiplusia gen. nov. (from Brunei), B. kaspraki sp. nov., Gynapteromyia costaricensis sp. nov. (Costa Rica), G. furcata sp. nov. (Costa Rica), G. novaezealandiae sp. nov. (New Zealand), G. tasmanica sp. nov. (Australia), G. temburong sp. nov. (Brunei), G. tenuistylata sp. nov. (Brunei), Haplusia afrotropica sp. nov. (South Africa), Japoplusia gen. nov. (Japan), Jap. honshuensis sp. nov., Johnsonomyia scabra sp. nov. (Costa Rica), John. serrata sp. nov. (South Africa), Loboplusia gen. nov. (Costa Rica), L. zurqui sp. nov., Makrostyles gen. nov. (Costa Rica), Makr. terrifica sp. nov., Mikrostyles gen. nov. (Brunei), Mikr. angustilobata sp. nov., Mikr. latolobata sp. nov., Wahabia gen. nov. (Brunei), Wah. mantici sp. nov., and Wyattella japonica sp. nov. (Japan). A key to the genera of Diallactiini based on male characters is presented. Diallactiini are shown to be a remarkably diverse group in terms of adult morphology. The genitalia of some male Diallactiini represent the most strongly modified such structures known in Winnertziinae. Morphological novelties found in Diallactiini, but no other Cecidomyiidae, include the fringed leg setae of Loboplusia and the furcate palpal sensilla in some Gynapteromyia and Mikrostyles. Diallactiini occur in all zoogeographic regions, with the highest generic and specific diversity found in the tropics (although Afrotropical diallactiines are poorly researched). Local diversity is also highest in the tropics, with as many as 29 species (unnamed or named in this paper) of at least 6 genera found at a single site, Zurqui de Moravia, in the cloud forest of Costa Rica. The best-explored fauna of Winnertziinae, including Diallactiini, is certainly that of Europe, but diallactiine biodiversity there is low and most of the nine European species are rarely encountered in the field. Gynapteromyia brevipalpis is reported from Sweden for the first time. PMID- 27395623 TI - Review of the Hispaniolan Parachondria (Chondropomorus) complex (Gastropoda: Littorinoidea: Annulariidae). AB - The Parachondria (Chondropomorus) complex in Hispaniola is reviewed. Nineteen species are recognized including eight new species: Parachondria anatolensis n. sp., Parachondria arcisensis n. sp., Parachondria daedalus n. sp., Parachondria heatheraikenae n. sp., Parachondria isabellinus n. sp., Parachondria muchai n. sp., Parachondria silvaticus n. sp., and Parachondria stigmosus n. sp. Distributional and habitat notes are given for additional taxa. Chondropoma marinum "Weinland" Reeve, 1863, is regarded as a nomen dubium. Chondropoma (Chondropomorus) moroni Bartsch, 1946, is reidentified as Crossepoma emilianum (Weinland, 1862). Chondropoma simplex Pfeiffer, 1852, regarded by Bartsch (1946) as a Chondropomorus, is considered a Chondropoma. PMID- 27395624 TI - Taxonomic and nomenclatorial revision within the Neotropical genera of the subtribe Odontocheilina W. Horn in a new sense-16. Pentacomia (Mesochila) procera (Chaudoir), P. (M.) conformis (Dejean), and P. (M.) proceroides sp. nov. (Coleoptera: Cicindelidae). AB - Results of the author's revision of the type and other accessible specimens of the hitherto little known and partly confused species-complex of P. (M.) conformis (Dejean, 1831) and Pentacomia (Mesochila) procera (Chaudoir, 1860) are presented. Redescriptions of these externally similar species with lectotype designation of P. (M.) procera are provided, and a closely related species, P. (M.) proceroides sp. nov., is described as a new to science. The synonymy of Odontochila chaudoiri Dokhtouroff, 1887 with P. (M.) procera has been confirmed. Mesochila Rivalier, 1969, with type species Odontochila procera Chaudoir, 1860 (by original designation), is here provisionally maintained as a subgenus of Pentacomia Bates, 1872 (as originally and hitherto classified), although the present revision has disclosed diagnostic characters of a separate genus. The history of the taxonomy and distribution of these three very rare species, which are at present known only from the type specimens and several other, mostly historical specimens from Brazil, as well as illustrations in colour photographs of their habitus and diagnostic characters, are provided. PMID- 27395625 TI - Monogenoidea (Polyonchoinea: Dactylogyridae) parasitizing the gills of marine catfish (Siluriformes: Ariidae) inhabiting the Atlantic Amazon Coast of Brazil. AB - A parasitological survey of monogenoids infesting the gills of marine catfish (Ariidae) captured from the Atlantic coastal region of the Amazon Basin was carried out during the 2011-2013 period. The gills of 448 specimens involving twelve ariid species (29 Amphiarius rugispinis (Valenciennes), 52 Aspistor quadriscutis (Valenciennes), 74 Bagre bagre (Linnaeus), 16 Cathorops arenatus (Valenciennes), 13 Cathorops agassizii (Eigenmann & Eigenmann), 17 Cathorops spixii (Agassiz), 3 Cathorops sp., 13 Notarius grandicassis (Valenciennes), 14 Sciades couma (Valenciennes), 64 Sciades herzbergii (Bloch), 48 Sciades parkeri (Traill), 13 Sciades passany (Valenciennes), 92 Sciades proops (Valenciennes) were sampled. No monogenoids were found in Cathorops agassizi, Cathorops arenatus, Cathorops spixii, Cathorops sp. and Sciades parkeri, but the gills of the other sampled species were parasitized by at least one species of monogenoid. We identified four new species of Chauhanellus and one new species of Hamatopeduncularia: Chauhanellus hamatopeduncularoideum n. sp. from Amphiarius rugispinis and Sciades couma; Chauhanellus hypenocleithrum n. sp. from Sciades proops; Chauhanellus susamlimae n. sp. from Sciades herzbergii and Sciades passany; Chauhanellus velum n. sp. from Sciades couma, Sciades herzbergii and Sciades passany; and Hamatopeduncularia cangatae n. sp. from Aspistor quadriscutis and Notarius grandicassis. Four previously described species were reported for the first time parasitizing ariids from Atlantic Amazon: Chauhanellus neotropicalis Domingues & Fehlauer, 2006 from Amphiarius rugispinis, Aspistor quadriscutis, Notarius grandicassis and Sciades passany; Chauhanellus boegeri Domingues & Fehlauer, 2006 from Sciades couma and Sciades herzbergii; Hamatopeduncularia bagre Hargis, 1955 from Bagre bagre; and Neomurraytrematoides proops Zambrano & Anez 1993 from Sciades passany. The monotypic Neomurraytrematoides Zambrano & Anez 1993 was placed in synonymy with Neotetraonchus Bravo-Hollis, 1968 and its type-species, Neomurraytrematoides proops Zambrano & Anez 1993 was transferred to Neotetraonchus as Neotetraonchus proops (Zambrano & Anez 1993) n. comb. The morphology of the haptoral structures supports the transfer of Rhamnocercus seenghali Kumar, 2013 to Chauhanellus as Chauhanellus seenghali (Kumar, 2013) n. comb. PMID- 27395626 TI - Revision of the Anthidiellum Cockerell, 1904 of China (Hymenoptera, Apoidea, Megachilidae, Anthidiini). AB - The resin bees of the genus Anthidiellum Cockerell, 1904 are revised for China. Seven species are confirmed to occur in China including five new combinations: A. (Pycnanthidium) carinatum (Wu, 1962) comb. nov., A. (P.) coronum (Wu, 2004a) comb. nov., A. (P.) latipes (Bingham, 1897) comb. nov., A. (Clypanthidium) popovii (Wu, 1962) comb. nov., and A. (Anthidiellum) yunnanensis (Wu, 1962) comb. nov.. These five species had previously been classified as Trachusa (Paraanthidium), which is characterized by much larger-bodied bees (only four species of Trachusa (Paraanthidium) are confirmed to occur in China after this study; others reported in the literature were misplaced to genus). Additionally, Anthidiellum ludingensis Wu, 1993, and Anthidiellum (Anthidiellum) xinjiangensis Wu, 2004b, are removed from Anthidiellum forming the new combinations Pseudoanthidium (Pseudoanthidium) ludingense (Wu, 1993) and P. (P.) xinjiangense (Wu, 2004b), thus extending the range of the genus in China to include Sichuan. Illustrations and a key to known Chinese Anthidiellum species are provided. PMID- 27395627 TI - A new species of Leptestheria (Crustacea: Branchiopoda: Spinicaudata) from Western Maharashtra, India. AB - We describe a new species of Leptestheria from a rock pool in the Western Ghats of Maharashtra, India. This species is distinguished from all other Indian congeners by its distinct telson characters and occipital condyle. We also present a comparative table of useful morphological characters of all described Indian Leptestheria species. PMID- 27395628 TI - Illustrated redescription of Haliplus (Liaphlus) arrowi Guignot, 1936 (Coleoptera: Haliplidae) from the Western Ghats, India, and notes on the closely related H. angustifrons Regimbart, 1892. AB - In an ongoing survey of aquatic beetles, the crawling water beetles Haliplus (Liaphlus) arrowi Guignot, 1936 and Haliplus (Liaphlus) angustifrons Regimbart, 1892 were found only from four (three localities for H. arrowi and one locality for H. angustifrons) out of 85 localities sampled in and around the Western Ghats of Maharashtra. Digital images and scanning electron micrographs of diagnostic characters are provided for the first time for both the species. Intraspecific and interspecific variation in the elytral maculation of H. arrowi and H. angustifrons is illustrated. PMID- 27395629 TI - A new cavernicolous assassin bug of the genus Bagauda Bergroth (Heteroptera: Reduviidae: Emesinae) from the Western Ghats, India. AB - A new cavernicolous, thread-legged assassin bug, Bagauda ernstmayri sp. nov. (Hemiptera: Heteroptera: Reduviidae: Emesinae), collected from a cave near Satara, in the Western Ghats of Maharashtra, India, is described. Its interaction with the web of an uloborid spider Zosis geniculata (Olivier, 1789) (Araneae: Uloboridae) is discussed. PMID- 27395630 TI - Four new species of the genus Phryganogryllacris (Orthoptera, Gryllacrididae, Gryllacridinae) in China. AB - A taxonomic study of the genus Phryganogryllacris Karny, 1937 is presented. Four new species are described: Phryganogryllacris brevipennis sp. nov., Phryganogryllacris hubeiensis sp. nov., Phryganogryllacris sigillata sp. nov., Phryganogryllacris fanjingshanensis sp. nov.. A key to the species and the distributional data of Phryganogryllacris are provided. PMID- 27395631 TI - Track analysis of Oribatid mites (Acari: Oribatida) of the Subantarctic subregion of South America. AB - We analysed distributional data of 30 species of Oribatid mites of the Subantarctic subregion of southern South America in order to contribute to elucidate their biotic evolution. We constructed individual tracks for the species analysed, based on published and unpublished records. After superposing them we obtained six generalized tracks and five nodes. Four generalized tracks (T2, T3, T4 and T6) extend along and near the Andean ranges, whereas two generalized tracks (T1 and T5) may be artefacts caused by the lack of information. The generalized tracks and nodes show the complex relationships of the austral biota, as hypothesized in previous contributions based on other plant and animal taxa. PMID- 27395632 TI - The Pselaphinae (Coleoptera: Staphylinidae) of Madagascar. V. Description of Squamiger elegans gen. et sp. nov. from Central Madagascar. AB - Squamiger elegans, gen. and sp. nov., is described based on a series of specimens collected by sifting of leaf-litter in Ambohitantely Special Reserve, Central Madagascar. The genus is a member of the tribe Clavigerini (Pselaphinae: Clavigeritae) and it is placed into the subtribe Clavigerodina. PMID- 27395633 TI - Morphological data support the recognition of four species in the genus Sirystes Cabanis & Heine, 1859 (Aves: Tyrannidae). AB - Sirystes is a widespread genus in the Neotropical region. Historically, five subspecies were recognized in a single widespread species, but more recently four separate species have been recognized, based on vocalizations and limited morphological data. In this paper, we analyze individual and geographic variation in this genus on the basis of body measurements and plumage coloration of 514 specimens, including all name-bearing types available. We conclude that the four recently proposed species, S. sibilator, S. albogriseus, S. albocinereus, and S. subcanescens, can also be diagnosed by morphological data, corroborating more recent taxonomic treatments. We identified possible hybrids between S. sibilator and S. albocinereus from a narrow zone of contact in central Bolivia. We show that Sirystes sibilator atimastus Oberholser, 1902 represents a point on a cline within S. sibilator (Vieillot, 1818), and it is here regarded as a subjective junior synonym of the latter. We also provide new observations on the range and diagnosis of S. subcanescens, a name that has been frequently misused, and present a redescription of the four recognized species, as well as reviewing their range and natural history. PMID- 27395634 TI - Revision of Neocolochelyna Malaise (Hymenoptera: Tenthredinidae). AB - Neocolochelyna Malaise, 1937 is revised. Curvatapenis Wei, 2002 is treated as a subgenus of Neocolochelyna. The genus and its type species, N. montana Konow, 1898, as well as N. (C.) itoi Takeuchi, 1951 and N. (C.) testaceoa Wei, 2002 are redescribed based on types and new material. N. (N.) acutilabria Niu & Wei sp. nov., N. (C.) hyalina Niu & Wei sp. nov. and N. (C.) wui Niu & Wei sp. nov. are described. Neocolochelyna hakusana Togashi, 1995 is a new synonym (syn. nov.) of N. itoi Takeuchi, 1951. Neocolochelyna (Curvatapenis) testaceoa (Wei, 2002) is a new combination (comb. nov.). A key to species of Neocolochelyna is provided. PMID- 27395635 TI - Revision of Colochela (Hymenoptera, Tenthredinidae). AB - Colochela Malaise, 1937 is removed from synonymy with Neocolochelyna Malaise, 1937, and re-established. The genus and its type species C. rufidorsata Malaise, 1937 are redescribed based on types and new material. C. nigrata Wei & Niu, sp. nov. and C. zhongi Wei & Niu, sp. nov. are described. A key separating Colochelyna Konow, 1898, Colochela and Neocolochelyna, and a key to species of Colochela are provided. Colochela and C. rufidorsata are new records for Nepal and Thailand. The distribution of Colochela is briefly discussed. PMID- 27395636 TI - Revised diagnosis of the genus Gonorhynchus McClelland (Teleostei: Cyprinidae: Labeonini) with redescription of G. latius (Hamilton) and revalidation of G. wattanah (Sykes). AB - A new diagnosis of the genus Gonorhynchus McClelland 1838 from South Asia is proposed. Seven species are contained in the genus: G. latius (Hamilton 1822), G. diplochilus (Heckel 1838), G. wattanah (Sykes 1839), G. macmahoni (Zugmayer 1912), G. burmanicus (Hora 1936), G. bicornis (Wu 1977), and G. periyarensis (Menon & Jacob 1996). Gonorhynchus latius, a senior synonym of the type species G. brevis M'Clelland 1839 is redescribed. Crossocheilus gohama (M'Clelland 1839) and Crossochilus rostratus Gunther 1868 are considered junior synonyms of G. latius, and a neotype is designated for G. latius. Gonorhynchus wattanah (Sykes 1839) from the Krishna and Godavari River basins in western India is revalidated and redescribed with the designation of a neotype. Akrokolioplax Zhang & Kottelat 2006 is a junior synonym of Gonorhynchus. PMID- 27395637 TI - Soil mites of the families Ascidae, Blattisociidae and Melicharidae (Acari: Mesostigmata) from mountainous areas of Colombia. AB - Soil mites of the Ascidae sensu Lindquist & Evans (1965) are poorly known in Colombia. This group, presently represented by the families Ascidae sensu stricto, Blattisociidae and Melicharidae, contains species known to prey on small arthropods and nematodes, thus having the potential to be used for the control of soil pests. The aim of this study was to identify species of this group from a fragment of Andean forest and a nearby grassland at the municipality of La Calera, Cundinamarca Department, Colombia, at about 2800 m of elevation. Nine species were found, including five new species, namely Gamasellodes andinus sp. nov., Gamasellodes intermedius sp. nov., Protogamasellus caleraensis sp. nov., Cheiroseius mesae sp. nov. and Proctolaelaps colombianus sp. nov. Morphological characterisation of all the species and relevant soil characteristics of the sites where the mites were collected are presented. PMID- 27395638 TI - Larval morphology and complex vocal repertoire of Rhacophorus helenae (Anura: Rhacophoridae), a rare flying frog from Vietnam. AB - We present new data on the distribution, reproduction, larval morphology and vocalization of Rhacophorus helenae (Rhacophoridae), a narrowly distributed frog from southern Vietnam. Two new populations of R. helenae were discovered during field surveys in the lowland monsoon forests in Dong Nai and Ba Ria-Vung Tau provinces in 2010-2013. Spawning was observed in May 2013. Egg clutches containing small (2.3+/-0.1 mm) unpigmented eggs were embedded in a foam nest and suspended high on trees above temporary ponds. The tadpoles of R. helenae have a morphology typical of pond-dwelling Rhacophorus larvae with a moderate tail length and a labial tooth row formula of 5(2-5)/3. Postmetamorphic juveniles differed from adult frogs in the features of their coloration and less developed webbing. The complex vocal repertoire of R. helenae included five types of tonal, wideband and pulsed calls and several transitional signal types differentiated by frequency and amplitude parameters. Calls were uttered as singular signals (pulsed calls) or within non-stereotyped series of variable duration (other call types). The complex structure of the advertisement call markedly distinguishes R. helenae from other members of the Rhacophorus reinwardtii species complex. PMID- 27395639 TI - The North African sawfly genus Prionomeion (Hymenoptera, Diprionidae), with a key to the Palaearctic genera of the subfamily Diprioninae. AB - The diagnostic characters are discussed for the North African genus Prionomeion Benson, 1939 (Hymenoptera, Diprionidae, Diprioninae). The type species, Prionomeion gaullei (Konow, 1906), is redescribed based on the holotype (female) and one male, both from Algeria. The second species of the genus, P. maghrebense sp. nov. is described based on one female from Morocco and one male from Algeria. A key to the Palaearctic genera of the subfamily Diprioninae is given. PMID- 27395640 TI - Micromorphological differentiation of left and right stridulatory apparatus in crickets (Orthoptera: Gryllidae). AB - The present study compared micromorphological differentiation of stridulatory apparatus between the functional right tegmen and non-functional left tegmen, analyzed under scanning electron microscope (SEM), among eight Gryllidae species. The results showed that the main differences were found on the length and shape of files and teeth. The length of stridulatory file and teeth number were lower on the left stridulatory apparatus than that on right stridulatory apparatus in all species. However, the ratio between the length of stridulatory teeth and the interval of stridulatory teeth was significantly higher on the left stridulatory apparatus than that on right stridulatory apparatus in Dianemobius fascipes, Polionemobius taprobanensis, Pteronemobius gifuensis, Teleogryllus occipitalis and Oecanthus longicauda. In addition, the length of stridulatory teeth was positively related to number of stridulatory teeth, however, the interval of stridulatory teeth was negatively related to the ratio between the length of stridulatory teeth and the interval of stridulatory teeth for left and right stridulatory apparatus. Our result illustrated that the length of left and right stridulatory file and teeth length could be an effective character to distinguish species. Left stridulatory apparatus was not entirely degraded than right stridulatory apparatus. PMID- 27395641 TI - Pelopscreadium aegyptense n. gen., n. sp. and Pelopscreadium spongiosum (Bray & Cribb, 1998) n. comb., (Digenea: Lepocreadiidae), each from disjunct populations of the Yellow boxfish, Ostracion cubicus Linnaeus (Ostraciidae). AB - Bianium spongiosum Bray & Cribb, 1998 (Lepocreadiidae), described from the yellow boxfish, Ostracion cubicus Linnaeus (Ostraciidae), off Lizard Island, Queensland, Australia, possesses a combination of the following three morphological features which distinguishes it from all the other species currently assigned to the genus: (1) large internal patches of large cells forming sponge-like pads we have termed "pelops"("pelop" sing.) laterally in the forebody extending from near the anterior extremity to about the level of the intestinal bifurcation rather than possessing a scoop; (2) ceca that reach to near the posterior extremity where they end blindly without ani; and (3) a vitellarium which is present laterally but not dorsal to the ceca. Based on this we propose the erection of Pelopscreadium n. gen. (Lepocreadiidae) with the assignment of B. spongiosum to this new genus as the type-species, Pelopscreadium spongiosum (Bray & Cribb, 1998) n. comb. Pelopscreadium aegyptense n. sp., also from the yellow boxfish but from the Red Sea off Sharm El-Naga, Egypt, is described as the second member of the new genus because it shares these three characteristics with P. spongiosum. PMID- 27395642 TI - Molecular analysis of six Rhynchospio Hartman, 1936 species (Annelida: Spionidae) with comments on the evolution of brooding within the group. AB - Rhynchospio Hartman, 1936 is a small group of spionid polychaetes currently comprising ten described species distributed mainly in the Pacific. Five species examined to date are hermaphrodites producing spermatozoa with long nuclei, oocytes with thin and smooth envelopes, and dorsally brooding their offspring. Since our first molecular analysis of four Rhynchospio species, we have collected additional material from Northern Territory, Australia, and Oregon, USA. Herein, we describe the gamete and adult morphology of the newly collected material and use molecular analyses to provide new insight on the phylogenetic relationships of six Rhynchospio species. Adults of R. cf. foliosa from Oregon are hermaphrodites, but in contrast to other Rhynchospio, they produce spermatozoa with short nuclei (ect-aquasperm), oocytes with thick vesiculate envelopes, and likely have a holopelagic larval development. Analysis of four gene fragments, comprising mitochondrial 16S rDNA, and nuclear 18S, 28S rDNA, and Histone 3 (2516 bp in total) showed Rhynchospio to be a monophyletic group, with R. cf. foliosa being a distant sister to the five other species. Rhynchospio cf. foliosa was closer to M. arctia having ect-aquasperm and vesiculate thick-envelop oocytes (p = 14.40%) than to Spioninae members B. proboscidea and P. elegans, having introsperm and oocytes with thin and smooth envelopes (p = 15.39 and 16.54%, respectively). We hypothesize that brooding might have evolved from free-spawning inside the Rhynchospio clade, but this hypothesis should be tested in a future analysis. PMID- 27395643 TI - New and newly recorded micro-caddisfly species (Insecta: Trichoptera: Hydroptilidae) from Australia's north, including islands of Torres Strait. AB - From the north of Australia's Northern Territory, far northeastern Queensland and Torres Strait Islands, six new species of microcaddisfly are described: Hydroptila roperi sp. nov., Hellyethira khukri sp. nov., Oxyethira (Trichoglene) bamaga sp. nov., Oxyethira (Dampfitrichia) torresiana sp. nov., Orthotrichia pethericki sp. nov., and Orthotrichia becca sp. nov. Oxyethira torresiana is recorded from the northwest of York Peninsula and Badu Island in the Torres Strait as well as from Papua New Guinea. Northern Australian records are given for Orthotrichia veikaba Wells and Orthotrichia ensiformis Wells, previously known only from Papua New Guinea. Northern Australian distributions are extended eastwards for Tricholeiochiton jabirella Wells and westwards for Oxyethira (Trichoglene) triangulata Wells, until now recorded only from the Northern Territory and northeastern Australia, respectively. Brief notes are given on collecting methods and sites. PMID- 27395644 TI - Studies on Neotropical Phasmatodea XVI: Revision of Haplopodini Gunther, 1953 (rev. stat.), with notes on the subfamily Cladomorphinae Bradley & Galil, 1977 and the descriptions of a new tribe, four new genera and nine new species (Phasmatodea: "Anareolatae": Phasmatidae: Cladomorphinae). AB - The anareolate New World subfamily Cladomorphinae Bradley & Galil, 1977 is reviewed and keys to the six tribes currently included are presented; these are: Cladomorphini Bradley & Galil, 1977, Cladoxerini Karny, 1923, Cranidiini Gunther, 1953, Pterinoxylini n. trib., Hesperophasmatini Bradley & Galil, 1977 and Haplopodini Gunther, 1953 rev. stat.. New diagnoses are presented for all these tribes and possible relationships within Cladomorphinae are discusssed. Morphology of the genitalia and egg-structures indicate Cladomorphinae as presently treated to be polyphyletic. Two subordinate groups are recognized within present Cladomorphinae, which differ considerably in numerous morphological characters of the insects and eggs. The first group and here regarded as Cladomorphinae sensu stricto is formed by the mostly South American Cladomorphini + Cranidiini + Cladoxerini, while the second group is formed by the predominantly Caribbean Hesperophasmatini + Pterinoxylini n. trib. + Haplopodini. Members of the first group (= Cladomorphini sensu stricto) share the dorsally carinate basitarsus in which the two dorsal carinae are melted with another, increasingly elongated gonapophyses VIII of females which are noticeably longer than gonapophyses IX and lamellate as well as strongly displaced medioventral carina of the profemora. Cranidiini + Cladomorphini share the strongly elongated and filiform gonapophyses VIII and presence of gonoplacs in the females, specialized poculum of males and presence of a median line in the eggs. Cranidiini differs from all other tribes of Cladomorphinae by the entirely unarmed legs of both sexes, distinctly broadened and leaf-like body and prominent longitudinal keel of the mesosternum of females, prominently enlarged poculum and spinulose phallus of males as well as the conspicuous narrowing of the posteromedian gap of the internal micropylar plate of the eggs and noticeably separated median line. Cladomorphini is characteristic for the specialized vomer and poculum of males and distinct opercular structures of the eggs. Certain representatives of Cladomorphini indicate relationships to the "Phanocles-group" of Diapheromerinae: Diapheromerini, hence Cladomorphini as presently treated may be paraphyletic. The exclusively South American Cladoxerini (= Baculini n. syn.) differs from the other two tribes of Cladomorphinae sensu stricto by the distinctly serrate profemora of both sexes and conspicuously shortened antennae of females, which consist of less than 30 segments and are much shorter than the profemora in females. Genital morphology, such as the elongated gonapophyses VIII and presence of gonoplacs in females, as well as the lamellate medioventral carina of the profemora indicate close relation to Cladomorphini. Cranidiini appears to be the sister-taxon of Cladomorphini + Cladoxerini. The tribe Baculini Gunther, 1953 is synonymised with Cladoxerini (n. syn.), on the basis that the type-genera of both tribes are congeneric, with Baculum Saussure, 1861 being a junior synonym of Cladoxerus St. Fargeau & Audinet-Serville, 1827 (n. syn.). The genus Tersomia Kirby, 1904 is removed from Hesperophasmatini and transferred to Cladoxerini. Wattenwylia Toledo Piza, 1938 is removed from Pachymorphinae: Gratidiini and transferred to Cladoxerini. A detailed new diagnosis is presented for Cranidiini along with a detailed differentiation and the tribe is shown to be monotypical, only containing its type-genus Cranidium Westwood, 1843. All Caribbean genera subsequently added to Cranidiini are removed and transferred to Haplopodini rev. stat.. The three tribes Hesperophasmatini + Pterinoxylini n. trib. + Haplopodini rev. stat. are closely related and might form a monophyletic clade within Cladomorphinae sensu lato. They differ from Cladomorphinae sensu stricto by the short gonapophyses VIII and reduced gonoplacs of females, unspecialized poculum of males and lack of a micropylar line in the eggs. Haplopodini Gunther, 1953 is re-established (rev. stat.) and comprises almost exclusively Caribbean genera previously placed in Hesperophasmatini by Bradley & Galil (1977) or Cranidiini by Zompro, (2004). Aploploides Rehn & Hebard, 1938, Diapherodes Gray, 1835, Haplopus Burmeister, 1838 and Paracranidium Brock, 1998 were misplaced in Cranidiini and are transferred to Haplopodini. On the basis of numerous morphological characters of the insects and eggs Hesperophasmatini is removed from Pseudophasmatidae: Xerosomatinae and re-transferred to its previous position in the subfamily Cladomorphinae sensu lato. A detailed newdiagnosis of Hesperophasmatini is presented, but is only provisional since the true diversity is as yet only fractionally known. The lack of a gula distinguishes Hesperophasmatini from all other tribes. The genus Laciphorus Redtenbacher, 1908 is removed from Hesperophasmatini and transferred to Diapheromeridae: Diapheromerinae: Diapheromerini. The new tribe Pterinoxylini n. trib. is established to contain only the type-genus Pterinoxylus Audinet-Serville, 1838. It is closely related and perhaps the sister taxon of Hesperophasmatini, with which it shares the presence of rough sensory areas on the probasisternum and profurcasternum. It differs from Hesperophasmatini and Haplopodini by the presence of a tympanal region (= stridulatory organ) in the alae of females and the alveolar eggs, which possess peripheral opercular and polar structures. Haplopodini is likely to be the sister group of Pterinoxylini n. trib. + Hesperophasmatini. The tribe Haplopodini rev. stat. is revised at the species level and comprises eight almost exclusively Caribbean genera, four of which are newly described. All eight genera now contained in Haplopodini are described in detail, differentiated from their closest relatives and their relationships and systematic position within Haplopodini are discussed. Keys and maps showing their distributions are presented along with a discussion of the distributional patterns. Detailed descriptions, differential diagnoses, synonymic listings, illustrations, material listings and measurements are given of all 26 currently known species and subspecies of Haplopodini. Four new genera are described within Haplopodini. The monotypical Apteroplopus n. gen. (type-species: Dyme grosse tuberculata Brunner v. Wattenwyl, 1907) from Honduras is the only taxon of the tribe represented in Central America. It is only known from the male which differs from all other genera by being entirely apterous. Cephaloplopus n. gen. (type-species: Cephaloplopus pulchellus n. sp.) and Parhaplopus n. gen. (type species: Haplopus cubensis Saussure, 1868) occur only on Hispaniola and Cuba. Both are closely related to Haplopus Burmeister, 1838 but in addition to having noticeably different eggs, both genera differ from Haplopus in several morphological characters. The monotypical Venupherodes n. gen. (type-species: Platycrana venustula Audinet-Serville, 1838) is endemic to Cuba, and in females being apterous resembles the second exclusively Cuban genus Aploploides Rehn & Hebard, 1938. It however differs from all other members of Haplopodini by the laterally expanded mesonotum of females, which overlaps the mesopleurae, as well as the morphology of the eggs. Two species-groups are recognized within Diapherodes Gray, 1835. The gigantea species-group comprises the species from the Lesser Antilles, which are: D. angulata (Fabricius, 1793), Diapherodes dominicae (Rehn & Hebard, 1938), D. gigantea gigantea (Gmelin, 1789), D. gigantea saintluciae n. ssp. and Diapherodes martinicensis Lelong & Langlois, 2005. The three species of the jamaicensis species-group, which are D. achalus (Rehn, 1904), D. jamaicensis (Drury, 1773) and D. laevicollis Redtenbacher, 1906, are restricted to the two Greater Antillean islands Jamaica and Puerto Rico. Haplopus Burmeister, 1838 is the most widely distributed genus being represented on all islands of the Greater Antilles except Jamaica, and also in the Virgin Islands, Bahamas, Florida Keys, Dry Tortugas and as far southwest as the Cayman Islands and Swan Islands. Nine new species and one new subspecies are described: Cephaloplopus alope n. sp. and Haplopus sobrinus n. sp. from Cuba, Cephaloplopus euchlorus n. sp., Cephaloplopus laetus n. sp., Cephaloplopus pulchellus n. sp., Haplopus brachypterus n. sp., Haplopus intermedius n. sp. and Parhaplopus navarroi n. sp. from Hispaniola, Haplopus woodruffi n. sp. from Cayman Brac (Cayman Islands) and Diapherodes gigantea saintluciae n. ssp. from Saint Lucia. Seven of these are described from both sexes but Cephaloplopus alope n. sp. and Haplopus sobrinus n. sp. are only known from the females and Cephaloplopus laetus n. sp. only from the males. The previously unknown males of Diapherodes angulata (Fabricius, 1793), Diapherodes laevicollis Redtenbacher, 1908, Haplopus bicuspidatus de Haan, 1842 and Parhaplopus cubensis (Saussure, 1868) as well as the previously unknown female of Parhaplopus evadne (Westwood, 1859) n. comb. are described and illustrated for the first time. Descriptions and illustrations of the eggs of eleven species are presented: Cephaloplopus euchlorus n. sp., Cephaloplopus pulchellus n. sp., Diapherodes achalus (Rehn, 1904), Diapherodes dominicae (Rehn & Hebard, 1938), Diapherodes gigantea gigantea (Gmelin, 1789), Diapherodes martinicensis Lelong & Langlois, 2005, Diapherodes jamaicensis (Drury, 1773), Haplopus bicuspidatus de Haan, 1842, Haplopus micropterus St. Fargeau & Audinet-Serville, 1825, Parhaplopus navarroi n. sp. and Venupherodes venustula (Audinet-Seville, 1838) n. comb.. Type specimens of the newly described taxa are deposited in the collections of ANSP, NHMUK, IIBZ, FSCA, MCZC, MNHN and USNM. Six species are transferred to other genera (n. comb.): Bacteria grossetuberculata (Brunner v. Wattenwyl, 1907) to Apteroplopus n. gen. (ABSTRACT TRUNCATED) PMID- 27395645 TI - A species checklist of the millipedes (Myriapoda, Diplopoda) of India. AB - At present, the millipede fauna of India comprises over 270 nominate species or subspecies in at least 90 genera, 25 families and 11 orders. As complete a catalogue as possible is compiled of all species or subspecies of Diplopoda formally reported from India, some of which remain dubious. Additionally, a checklist is also compiled of millipedes that have erroneously been recorded in India. Given also several literature lacunae, as well as numerous taxonomic problems, the number of species and even genera cannot be claimed precise. The following new transfers are proposed: Delarthrum pumilum (Attems, 1944), comb. n. ex Dasypharkis Attems, 1936; Stemmiulus crassipes (Carl, 1941), S. insolitus (Carl, 1941), S. mulierosus (Carl, 1937), S. plumipes (Carl, 1941) and S. vagans (Carl, 1941), all comb. n. ex Diopsiulus Silvestri, 1897; Cryptocorypha riparia (Carl, 1932), comb. n. ex Archandrodesmus Carl, 1932. A new record of Stenobolus insularis Carl, 1918 is given from India. PMID- 27395646 TI - Description of fourty four new species, taxonomic notes and identification key to Neotropical Trichomyia Haliday in Curtis (Diptera: Psychodidae, Trichomyiinae). AB - Trichomyia Haliday in Curtis is distributed worldwide, except in Antarctica. The Neotropical region has the greatest known species richness of Trichomyia, with 76 described species, compared with five in the Nearctic region, nine in the Palearctic, five in the Afrotropical region, six in the Oriental region, and 46 in the Australasian region. Two morphological groups within the genus have been previously recognized: Group A, comprising species with four clearly differentiated palpus segments; and Group B, comprising species with three palpus segments, as well as a group of species with four palpus segments but with the two basal segments not fully articulated (partially fused). We examined 1,330 specimens of Trichomyia that were collected almost exclusively from Brazil, specifically from the states of Amazonas, Para, Bahia, Roraima, Rondonia, and Minas Gerais. 44 new species have been identified, representing an increase of 37% for this genus in the Neotropical region. In order to facilitate their study, some species are placed in provisional morphological groups. The distributions of five species of Trichomyia are expanded and a key to the males of Neotropical species is presented. PMID- 27395647 TI - Decapod crustaceans from the state of Ceara, northeastern Brazil: an updated checklist of marine and estuarine species, with 23 new records. AB - The present study is the first major assessment of the marine decapod fauna of Ceara, northeastern Brazil, since contributions of J. Fausto-Filho in the 1960s 1970s. A fully updated checklist of all decapod crustaceans occurring in marine and estuarine habitats of Ceara is provided, based on literature records, specimens held in two carcinological collections of the Universidade Federal do Ceara (UFC), and material collected mainly by the authors between 2011 and 2014. A total of 337 decapod species are listed, distributed among the following taxa: Achelata (8 species), Anomura (42 species), Astacidea (1 species), Axiidea (11 species), Brachyura (162 species), Caridea (83 species), Dendrobranchiata (20 species), Gebiidea (9 species), and Stenopodidea (1 species). Among them, 23 species represent new records for Ceara, with 14 species, viz. Alpheus peasei (Armstrong, 1940), A. thomasi Hendrix & Gore, 1973, Ambidexter symmetricus Manning & Chace, 1971, Axianassa australis Rodrigues & Shimizu, 1992, Biffarius biformis (Biffar, 1971), B. fragilis (Biffar, 1970), Leptalpheus axianassae Dworschak & Coelho, 1999, L. forceps Williams, 1965, Lysmata bahia Rhyne & Lin, 2006, L. intermedia (Kingsley, 1878), Merhippolyte americana Holthuis, 1961, Neocallichirus maryae Karasawa, 2004, Ogyrides hayi Williams, 1981, and Typton carneus Holthuis, 1951, now having Ceara as the northern-most limit in their distribution range along the Brazilian coastline. One shrimp species, Lysmata lipkei Okuno & Fiedler, 2010, which was also found in the state of Rio Grande do Norte, possibly represents an invasive taxon in Brazil and the western Atlantic, originating from the Indo-West Pacific. Alpheus buckupi Almeida, Terossi, Araujo Silva & Mantelatto, 2013, previously recorded from Ceara based on a colour photograph, is confirmed from this state, with specimens from several new localities. A few doubtful records from Ceara are briefly discussed. Colour photographs are provided for most of the taxa newly recorded from Ceara; some species are illustrated in colour for the first time. PMID- 27395648 TI - Additions to Philippine Slender Skinks of the Brachymeles bonitae Complex (Reptilia: Squamata: Scincidae) I: a new species from Lubang Island. AB - A new species of slender skink is described from the Philippines. The species is endemic to Lubang Island, and is assigned to the Brachymeles bonitae Complex based on phenotypic and genetic data. Specimens were collected from Lubang Island between 1991 and 2012, and were examined based on morphological data (qualitative traits, meristic counts, and mensural measurements). Published genetic sequence data from phylogenetic studies of the genus reveal the new species to be highly divergent from congeners. Brachymeles ligtas sp. nov. is differentiated from other members of the genus based on a number of distinct morphological features, including small body size (SVL 60.7-79.6 mm), bidactyl fore-limbs, digitless hind limbs, high number of presacral vertebrae (50), and the absence of auricular openings. Additionally, the new species has diagnostic, distinct dorsal head scale patterns. This new species becomes the only member of the genus known to occur on the deep-ocean island of Lubang. PMID- 27395649 TI - Additions to Philippine Slender Skinks of the Brachymeles bonitae Complex (Reptilia: Squamata: Scincidae) II: a new species from the northern Philippines. AB - We describe a new digitless scincid lizard of the genus Brachymeles from northern Luzon and Camiguin Norte islands in the Philippines. This species belongs to the Brachymeles bonitae Complex, and both molecular and morphological data confirm that this species is distinct from all other congeners. Formerly considered to be a single widespread species, this group of species has been the focus of recent systematic reviews. Here we describe a new species in the B. bonitae Complex, recognized currently to constitute five species. Brachymeles ilocandia sp. nov. is the second digitless and the seventeenth non-pentadactyl species in genus. The description of this species brings the total number of species in the genus to 40, and provides new insight into unique distribution patterns of species of the northern Philippines. PMID- 27395650 TI - Additions to Philippine Slender Skinks of the Brachymeles bonitae Complex (Reptilia: Squamata: Scincidae) III: a new species from Tablas Island. AB - Studies of the diversity of Philippine amphibians and reptiles have resulted in the continued description of cryptic species. Species formerly thought to range across multiple recognized faunal regions are now considered to be assemblages of multiple unique species, each restricted to a single faunal region. This pattern continues to hold true when considering Philippine skinks of the genus Brachymeles. Recent studies have resulted in the description of numerous unique species with many exhibiting various degrees of digit loss or limb reduction, as well as suggesting that unique lineages are still present in the B. bonitae Complex. In this paper, we describe a new species of fossorial skink within this species complex from Tablas Island based on collections made nearly 50 years ago. Although no genetic data are available for the new species, examinations of morphological data (qualitative traits, meristic counts, and mensural measurements) support its distinction from all other members of the genus. Brachymeles dalawangdaliri sp. nov. is differentiated from other members of the genus based on a suite of unique phenotypic characteristics, including a small body size (SVL 66.0-80.9 mm), bidactyl fore-limbs, digitless, unidactyl, or bidactyl hind limbs, a high number of presacral vertebrae (49), the absence of auricular openings, and distinct dorsal head scale patterns. The description of the new species increases the diversity of endemic vertebrates recognized to occur in the Romblon Island Group in the central Philippines. PMID- 27395651 TI - The Westpalaearctic Lasius paralienus complex (Hymenoptera: Formicidae) contains three species. AB - Application of Numeric Morphology-Based Alpha-Taxonomy (NUMOBAT) demonstrated the existence of three cryptic species within the Westpalaearctic Lasius paralienus species complex: L. paralienus Seifert, 1992, having a wider European distribution north to Sweden, L. casevitzi sp. nov., an endemic of Corsica, and Lasius bombycina sp. nov. from southeast Central Europe, the Balkans and Asia Minor. Hierarchical NC-Ward clustering and non-hierarchical NC-k-means clustering of 16 morphological characters resulted in 98.7% identical classifications within 76 examined nest samples of the three species. The classification error in 180 worker individuals was 0% in a linear discriminant analysis (LDA) and 1.3% in a LOOCV-LDA. Differential characters to other species groups and an identification key of the six European members of the Lasius alienus Forster species group are provided. PMID- 27395652 TI - Molecular characterisation of five nematode species (Chromadorida, Selachinematidae) from shelf and upper slope sediments off New Zealand, with description of three new species. AB - Limited molecular sequence data are available for selachinematid nematodes, with little or no data from the Southern Hemisphere or habitats beyond the subtidal zone. Here, we provide molecular sequence data for the small subunit (SSU) 18S rDNA gene and D2-D3 region of large subunit (LSU) 28S rDNA gene of three new (Cheironchus haurakiensis n. sp., Halichoanolaimus anisospermus n. sp., and Bendiella longicauda n. sp.) and two known selachinematid species (Pseudocheironchus ingluviosus Leduc, 2013 and Synonchiella rotundicauda Leduc, 2013) from shelf and upper slope environments off northeastern New Zealand. Cheironchus haurakiensis n. sp. is characterised by having a multispiral amphideal fovea with five turns, lateroventral mandibles with central arm curved distally and bearing 4-5 pointed projections, and each palm bearing 4-5 pointed projections, ten precloacal supplements in a 1 + 9 arrangement, spicules 78 um long, and blunt conical tail with thickened cuticle. Halichoanolaimus anisospermus n. sp. is characterised by having an amphideal fovea with 5-6 turns, anterior portion of buccal cavity with cuticularised rhabdions terminating in three sets of seven pairs of teeth (denticles), with the central pair of each set positioned above the other six, dimorphism in size of sperm cells between anterior and posterior testes, gubernaculum consisting of two detached lateral pieces (crurae) tapering distally, three small precloacal supplements consisting of slightly thickened and raised cuticle, and a conicocylindrical tail with conical portion 32-38% of total tail length. Bendiella longicauda n. sp. is characterised by having two dorsosublateral rows of pores from midbody to level of cloaca, amphideal fovea with 4.5 turns, posterior rhabdions with numerous small denticles, spicules 2.1 cloacal body diameters long, a conicocylindrical tail 13.3 cloacal body diameters long and with conical portion 8% of tail length. Preliminary phylogenetic analyses for the family Selachinematidae do not provide evidence of clustering according to depth (intertidal/subtidal vs shelf/upper slope) or geographical location (New Zealand vs Northern Hemisphere). The number of available Selachinematidae sequences, however, remains limited and comprehensive analyses based on larger number of sequences will be necessary to provide more solid conclusions. PMID- 27395653 TI - Annotated checklist and key to species of Gryllotalpa (Orthoptera: Gryllotalpidae) from the Oriental region. AB - The cosmopolitan Gryllotalpa mole cricket is the most speciose genus (70 species) in the family Gryllotalpidae. The taxonomy and diversity of Oriental species are not well understood. A species list with 26 species is presented here. An artificial key is also presented aimed to help with species identification, new species discovery and future taxonomic revision in the biodiverse Oriental region. PMID- 27395654 TI - A new species of Polyandrocarpa (Ascidiacea, Styelidae) in the Mediterranean Sea. AB - Polyandrocarpa arianae n. sp. was collected repeatedly by trawls deeper than 90m from several parts of the Mediterranean Sea. It is described and compared to the shallow species Polyandrocarpa zorritensis (Van Name, 1931) considered as invasive in the Mediterranean Sea. Among the colonial Styelidae the other species which belong to the same genus differ by the colony and zooid shape, the presence/absence of endocarps and of a caecum in the gut loop and by the location and structure of the polycarps. PMID- 27395655 TI - Misidentification of Carcharhinus galapagensis (Snodgrass & Heller, 1905) in the Southwest Pacific Ocean. AB - Although primarily a coral reef species the grey reef shark Carcharhinus amblyrhynchos has been recorded from a number of subtropical oceanic islands and reefs in the Southwest Pacific Ocean. Examination of all nominal C. amblyrhynchos voucher material collected from Lord Howe Island, Elizabeth and Middleton Reefs and Norfolk Island resulted in the re-identification of these specimens as Galapagos sharks, C. galapagensis. As C. amblyrhynchos superficially resembles C. galapagensis visual records of C. amblyrhynchos from Elizabeth and Middleton Reefs and the Kermadec Islands cannot be substantiated without voucher material. Carcharhinus amblyrhynchos therefore appears to be confined to waters north of about 25o S in the Southwest Pacific. Precaudal vertebral counts should be used to confirm the identification of nominal C. amblyrhynchos specimens that have an interdorsal ridge. PMID- 27395656 TI - A new temperate deepwater skate of the genus Bathyraja (Rajoidei: Arhynchobatidae) from the South-West Pacific. AB - A single specimen of a new Bathyraja skate was collected by the authors in 2003 during a survey of the deepwater biota of the northern Tasman Sea by the New Zealand FRV Tangaroa. This skate, labelled the 'blonde skate' by voyage participants, is uniformly white on all surfaces of the body and the skin is partly translucent. It belongs to a subgroup of Bathyraja with a large, almost smooth, quadrangular disc and well-developed and equally spaced median tail thorns. Other similar and probably closely related Bathyraja specimens have been caught in seas to the south of New Zealand since the discovery of this species, but their identity is yet to be confirmed. PMID- 27395657 TI - Three new species of the leafhopper genus Drabescus Stal (Hemiptera: Cicadellidae: Deltocephalinae) from China. AB - Three new species of leafhoppers: Drabescus cuspidatus sp. nov., Drabescus convolutus sp. nov. and Drabescus multidentatus sp. nov. are described and illustrated from China. A key to 24 of the 30 known Chinese species of the genus is given. The type specimens of the new species are deposited in the Institute of Entomology, Guizhou University, Guiyang, China (GUGC). PMID- 27395658 TI - The "Italian hebrid", Hebrus franzi (Wagner, 1957): disentangling a half-century dilemma (Hemiptera: Heteroptera: Gerromorpha). AB - Hebrus franzi (Wagner, 1957) was described from the Apuan Alps (Tuscany, Italy) and not found again for several decades despite intensive search. We report on new collections that expand the known distribution area considerably, provide a redescription, and give first insights regarding the ecology of this remarkable flightless species. PMID- 27395659 TI - First record of Odontomesa Pagast from China, with description of the immature stages of O. ferringtoni Saether (Diptera, Chironomidae, Prodiamesinae). AB - The genus Odontomesa Pagast is newly recorded from China. Based on associated material collected from China and U.S.A, the immature stages of Odontomesa fulva (Kieffer) and Odontomesa ferringtoni Saether are redescribed. Odontomesa sp. A Saether is confirmed as conspecific with O. ferringtoni. The generic diagnosis of immature stages is emended. Keys to the known larvae and pupae of the genus are presented. PMID- 27395660 TI - A new species of the genus Oreonectes (Cypriniformes: Nemacheilidae) from Guizhou, China. AB - This study examined the morphological and phylogenetic characteristics of Oreonectes shuilongensis sp. nov. The genus Oreonectes is distributed only in southwestern China and northern Vietnam. Sixteen specimens of cavefish were captured in the Shuilong Township in Guizhou Province of China and identified as a new species of Oreonectes (Cypriniformes: Nemacheilidae). Maximum likelihood was used to construct phylogenetic trees based on data for Nemacheilidae species accessible on GenBank. Molecular phylogenetic analyses showed that O. shuilongensis is closely related to O. platycephalus from which it is distinguished by having 6 vs. 5 branched anal rays, ratio of body length to body height 7.0-7.9 vs. 5.6-7.0, ratio of head length to distance between eyes 3.5-4.9 vs. 2.0-2.4, naked vs. scaly body, densely distributed fine black stains except on abdomen, and semitransparent body. Oreonectes shuilongensis is the only species of the genus not distributed in Guangxi Province. This study has contributed to the overall knowledge about the distribution of Oreonectes. PMID- 27395661 TI - Taxonomic synopsis of Notiospathius Matthews & Marsh, 1973 (Hymenoptera: Braconidae) from Colombia. AB - Notiospathius Matthews & Marsh, 1973 is the second most diverse genus of Doryctinae in the Neotropical region, however, in Colombia only two species have been reported and no studies on the diversity of the genus have been conducted. We present a taxonomic synopsis of the genus from Colombia. Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA) allowed the taxonomic evaluation of morphometric characters used by other authors and those proposed in the present study to differentiate the species. Forty seven of 104 characters studied are useful to discriminate the species. Twenty three species are reported. The following new records for Colombia are: Notiospathius angustus Marsh, 2002; N. badius Marsh, 2002; N. bicolor Marsh, 2002; N. ninae Marsh, 2002; N. rugonotum Marsh, 2002; N. shawi Marsh, 2002; N. tinctipennis (Cameron, 1887) and N. venezuelae Lopez-Estrada & Zaldivar-Riveron, 2012. The following 14 new species are described: N. alejandroi sp. nov., N. amazonensis sp. nov., N. carmenae sp. nov., N. cundinamarcensis sp. nov., N. farallonensis sp. nov., N. julianoi sp. nov., N. magdalenensis sp. nov., N. marshi sp. nov., N. payae sp. nov., N. putumayensis sp. nov., N. quimbayensis sp. nov., N. tayronensis sp. nov., N. utriae sp. nov., N. vallensis sp. nov. Notiospathius ugaldei Marsh, 2002 is the junior synonym of N. columbianus (Enderlein, 1912); Notiospathius mariachi Resendiz-Flores, Nunes and Zaldivar-Riveron, 2014 is the junior synonym of N. carolinae (Marsh, 2002); and N. chinanteco Resendiz-Flores, Nunes and Zaldivar Riveron, 2014 is the junior synonym of N. rugonotum Marsh, 2002. A comprehensive taxonomic key with illustrations is presented. PMID- 27395662 TI - A new species of the genus Eremias Fitzinger, 1834 (Squamata: Lacertidae) from Central Iran, supported by mtDNA sequences and morphology. AB - A new species of the lacertid genus Eremias Fitzinger, 1834 is described from northwest of Isfahan province, Central Iran. Two mitochondrial genes (cyt b and 12S DNA) were sequenced and analyzed as reliable molecular markers for the separation of this newly discovered species from closely related species within the genus Eremias: E. velox, E. persica, E. papenfussi, E. lalezharica, E. montana, E. strauchi, E. kopetdaghica and E. suphani. Genetic distances (K2-p) between any of these species with the newly described species are relatively high (27.5-32.8% for cyt b and 5.2-10.4% for 12S DNA). Phylogenetic analyses (MP, ML and BI) generated trees with very similar topologies. According to molecular and morphological data, Eremias isfahanica sp. nov. belongs to the subgenus Aspidorhinus, and is closely related to E. papenfussi. Because several new Eremias species have recently been described from the Iranian Plateau, we additionally provide an updated identification key. PMID- 27395663 TI - A review of genus Nysius Dallas in Argentina (Hemiptera: Heteroptera: Orsillidae). AB - The orsillid genus Nysius Dallas is a complex and large genus with more than 100 described species worldwide, and includes many species of agricultural importance, one such example is N. simulans (Stal) from Argentina. Three species of Nysius are found in this country: N. simulans (Stal), N. irroratus (Spinola) and N. puberulus Berg. The material available for the present study, consisting of over 610 specimens, was collected by sweep-net, G-Vac and light trap in the provinces of Chubut (42 degrees to 46 degrees S; 63.5 degrees to 72 degrees W), La Pampa (35o to 39o south; 63o to 68o West), Neuquen (36 degrees to 41 degrees S; 68 degrees to 71 degrees W) and Rio Negro (37 degrees to 42 degrees S; 62 degrees to 71 degrees W), in the central region of Argentina, during the years 2010-2014. Although the species N. simulans is frequently recorded as a pest of soybean crop, there exist no detailed description but only a brief general diagnosis. In the present contribution, therefore, we provide a detailed redescription as well as an updated distribution of N. simulans and N. irroratus, and a key for species of genus Nysius present in Argentina. PMID- 27395664 TI - A taxonomic review of the genus Dolichomitus Smith (Hymenoptera: Ichneumonidae: Pimplinae) from South Korea with descriptions of two new species. AB - Nineteen species of the genus Dolichomitus Smith (Hymenoptera: Ichneumonidae: Pimplinae) are recognized from South Korea, including 15 newly recorded species as well as two species new to science, Dolichomitus koreanus sp. nov., and D. rufinus sp. nov., A key to the species of the genus Dolichomitus in South Korea is provided, together with diagnostic illustrations. PMID- 27395665 TI - Revision of the genus Pseudeurybata Hennig (Diptera, Micropezidae, Taeniapterinae). AB - The previously monotypic genus Pseudeurybata Hennig is revised to include seven species from Central America and Mexico and one species from South America. Pseudeurybata rufilabris (Enderlein) and Pseudeurybata compeditus (Hennig) are given as new combinations and a lectotype is designated for P. rufilabris (Enderlein). Pseudeurybata browni and P. alces from Costa Rica, P. guatemalensis from Guatemala, P. dasypogon from Mexico, and P. zeta from Colombia and Ecuador are described as new. All species are keyed and illustrated. PMID- 27395666 TI - Rediscovery of the holotype of Tetragonopterus vittatus Castelnau 1855, a senior synonym of Moenkhausia doceana (Steindachner 1887) (Characiformes: Characidae). AB - The description of Tetragonopterus vittatus presented by Francis L. Castelnau (1855) was very concise and apparently based on a single specimen (not explicitly stated in the text, but deducible according to the single counts for the meristic data presented in the description). The type locality is recorded simply as "Bahia", with no specification of the drainage or nearby city. The existence of type specimens has been considered unknown (Lima et al., 2003; Eschmeyer & Fricke, 2015; Lucena & Soares, 2016), and have not been mentioned in published catalogues for type specimens of MNHN (e.g. Bertin, 1948). PMID- 27395667 TI - Two new synonymies at the generic level in Neotropical Ptomaphagini (Coleoptera, Leiodidae, Cholevinae). AB - We here recognize the genus Excelsiorella (s. str.) Salgado, 2008 as a junior synonym of the genus Adelopsis Portevin, 1907, and Viruana Salgado, 2013, a subgenus of Excelsiorella, as a junior synonym of the genus Parapaulipalpina Gnaspini, 1996. As a consequence, we propose the following new combinations: Adelopsis latissima (Salgado, 2008) n. comb. (from Excelsiorella (s. str.)) and Parapaulipalpina tambopata (Salgado, 2013) n. comb. (from Excelsiorella (Viruana)). PMID- 27395668 TI - A new species of Rotigonalia (Insecta: Hemiptera: Cicadellidae) from Peru with a key to males of the genus. AB - Rotigonalia regina sp. nov. is described and illustrated based on a male specimen from Pasco, Peru. The holotype of R. regina is rather large in comparison with other specimens of the genus, but the inflated clypeus and the shape of the paraphyses support its inclusion in Rotigonalia Young, 1977. A key to males of the five known species of Rotigonalia is given. PMID- 27395669 TI - Notes on Scaphidium grande-complex with description of a new species from China (Coleoptera: Staphylinidae: Scaphidiinae). AB - A new species of the Scaphidium grande- complex, S. yuzhizhoui sp. n., collected from Guangdong Province is described and its diagnostic characters are illustrated. Scaphidium inflexitibiale Tang & Li, 2010 is recorded from Laos for the first time. PMID- 27395670 TI - The identity of Paradiopatra bihanica (Annelida: Onuphidae) and reinstatement of P. calliopae. AB - Examination of the holotype of Paradiopatra bihanica (Intes & LeLoeuff, 1975) indicated that the identity of this species had been incorrectly represented in recent papers and that the ensuing synonymisation of P. calliopae Arvanitidis & Koukouras, 1997 was unwarranted. This led us to researching the history of the holotype and its representation in the literature to reinstate P. calliopae as the correct name for this very common Mediterranean and eastern North Atlantic species (Martinez & Adarraga 2001; Arias & Paxton 2015; Santelli et al. 2015). PMID- 27395671 TI - On the Prepuna biogeographic province: A nomenclatural clarification. AB - The nomenclatural status of the Prepuna province sensu Cabrera (1951) and sensu Morrone (1999) is clarified. The Prepuna province sensu Cabrera (1951) is demoted to a district of the Monte province, stat. nov. The valid name of the Prepuna province sensu Morrone (1999) is Cuyan High Andean province Cabrera, 1971, stat. nov. Diagnoses of these areas are provided and their endemic taxa are listed. PMID- 27395672 TI - Description of the larva of Gynacantha millardi Selys, 1891 (Odonata: Aeshnidae) from Chhattisgarh, India. AB - The larva of Gynacantha millardi Selys is described here from female larvae and male and female exuviae collected from Chhattisgarh, India. Unlike other Gynacantha larvae known so far, G. millardi has 7 palpal setae almost equal in length; in other species, the palpal setae are of different lengths. The larvae lack a tooth on each side of the median cleft and have a distinct blunt tooth on the inner margin corner of each labial palp. The larvae were found in a semi stagnant forest pool with enormous growth of aquatic vegetation. PMID- 27395673 TI - The correct authorship and date of lizard names Teiinae, Tupinambinae,
and Gymnophthalmidae. AB - Teiidae and Gymnophthalmidae are lizard families endemic to the Neotropical region (Vitt & Caldwell 2014), with about 150 and 245 valid living species, respectively (Uetz & Hosek 2015). Extinct teiid taxa are known from the Cretaceous to the Holocene (Albino 2005; Estes 1983b; Sullivan & Estes 1997). The authorship of Teiidae is undoubtedly attributed to Gray (1827) (ICZN 1985), but there is some confusion in literature regarding its subfamilies Teiinae and Tupinambinae. The same is true for Gymnophthalmidae. We investigated those issues through a literature review, found the source of mistakes and suggest what we consider be the correct authorship and dates for those family-group names. PMID- 27395674 TI - Review of the genus Scythropiodes Matsumura, 1931 (Lepidoptera, Lecithoceridae, Oditinae) from China, with a checklist of the world. AB - The genus Scythropiodes Matsumura, 1931 in China is reviewed. Fifteen species are treated, including four new species: Scythropiodes aculeiformus sp. nov. from Sichuan, S. dorsoprocessus sp. nov. from Guangxi, S. asymmetricus sp. nov. from Guangxi and Yunnan, and S. taedus sp. nov. from Yunnan. The females of S. barbellatus and S. elasmatus are described for the first time. Images of adults and genitalia are provided. A key to all the involved species and three maps showing the distribution of these species are included. A checklist of Scythropiodes on a worldwide basis is given. PMID- 27395675 TI - Metalimnobia crane flies (Diptera: Limoniidae) from Korea. AB - Korean species of the crane fly genus Metalimnobia Matsumura, 1911 (Diptera: Limoniidae), are taxonomically revised. Metalimnobia (Metalimnobia) channpayna new species, is described and figured, M. (M.) bifasciata (Schrank, 1781), M. (M.) quadrinotata (Meigen, 1818) and M. (M.) zetterstedti (Tjeder, 1968) are listed for the first time in Korea, new information for previously known species, M. (M.) quadrimaculata (Linnaeus, 1760) is added. Identification key for all Korean Metalimnobia species is given. Wings, male and female terminalia are illustrated for all species. PMID- 27395676 TI - A new species of the Craugastor podiciferus species group (Anura: Craugastoridae) from the premontane forest of southwestern Costa Rica. AB - In this report, we describe a new species of the Craugastor podiciferus species group from the premontane forest of the Pacific versant along the Costa Rican Panamanian border. Mitochondrial DNA and karyotype analyses previously showed a marked genetic divergence between populations of the premontane forest of the Fila Costena and the lowlands South Pacific Costa Rica near Panama. Analyses of the mitochondrial DNA sequences and the morphological variation revealed significant differences between the populations of the premontane forest relative to the other populations of C. stejnegerianus, including the type locality. We recognize these premontane populations as a new species and show that they differ from the typical C. stejnegerianus in the coloration of the venter, the head and the body proportions, and mtDNA divergence. With the addition of this new species, the C. podiciferus species group now contains nine species. PMID- 27395677 TI - Parhyale darvishi, a new widely distributed amphipod species, in the Persian Gulf and the Gulf of Oman (Crustacea, Amphipoda, Hyalidae). AB - Parhyale darvishi sp. nov., is described. The new species is characterized by a naked posterior margin on the propodus of pereopods 5-7, a special arrangement of robust setae on the first male gnathopod and a lack of dense fine setae on the second antennae. Parhyale darvishi sp. nov. is distributed from the western coasts of the Persian Gulf to the eastern coasts of Gulf of Oman. PMID- 27395678 TI - New and little-known species of the genus Lacon Laporte, 1838 (Coleoptera: Elateridae) of China. AB - Two new species of the genus Lacon Laporte, 1838 are described from Yunnan province of China: L. diqingensis sp. nov. and L. lijiangensis sp. nov. Lacon salvazai (Fleutiaux, 1918) is recorded for the first time in China. The position of these species within the genus and their geographical distribution are discussed. A preliminary key to the known species of Lacon of mainland China is provided. PMID- 27395680 TI - Additions to the fauna of plume moths (Lepidoptera, Pterophoridae) of Uganda. AB - An overview of 20 Pterophoridae species from Uganda is given. Three of them are described as new to science: Crassuncus agassizi Ustjuzhanin & Kovtunovich sp. nov., Hellinsia anikini Ustjuzhanin & Kovtunovich sp. nov. and Hellinsia nawrothi Ustjuzhanin & Kovtunovich sp. nov. Twelve species are recorded as new to the fauna of Uganda. PMID- 27395679 TI - The genus Euurobracon Ashmead (Hymenoptera, Braconidae, Braconinae) in China, with description of three new species. AB - The species of the genus Euurobracon Ashmead (Hymenoptera, Braconidae, Braconinae) from China are revised and six species are recognized, including three new species (E. acuminatus sp. nov., E. disparalis sp. nov., and E. unicolor sp. nov.), which are described and illustrated. Also, E. triplagiata (Cameron, 1900), is reported from China for the first time. A key to the Chinese species of this genus is provided. PMID- 27395681 TI - Three eriophyoid mite species (Acari: Eriophyoidea: Eriophyidae) from Iran. AB - Three mite species of the family Eriophyidae from Iran are described and illustrated. They are: Tegolophus marrubiumer sp. nov. on Marrubium vulgare L. (Lamiaceae); Phyllocoptes sp. cf. balasi Farkas, 1962 on Sanguisorba minor Scop. subsp. minor (Rosaceae) and Aceria fasciculifolis sp. nov. on Astragalus fasciculifolius Boiss. (Fabaceae). Both new species described herein are vagrants on their respective host plants. PMID- 27395683 TI - Two new species of the sharpshooter genus Oragua Melichar, 1926 from Southeastern Brazil (Hemiptera: Cicadellidae: Cicadellini). AB - Two very similar new species of Oragua Melichar, 1926, O. linnavuorii sp. nov. and O. flavolineata sp. nov., are described and illustrated from the Atlantic Forest of Southeastern Brazil (Mantiqueira mountain range). The new species share the presence of a large dentiform process located posteroventrally on the male pygofer, a unique feature within the genus. They can be distinguished from each other by the paraphyses with a pair of elongate, slender asymmetrical rami in O. linnavuorii and with two pairs of short, spiniform apical processes in O. flavolineata. The male of O. linnavuorii is macropterous but the female is submacropterous and thus smaller than the former when specimens are measured from the apex of the crown to the tips of the forewings at rest. The female of O. flavolineata is not known. Male holotypes are deposited in DZRJ. A key to males of the five Oragua species recorded from Southeastern Brazil is provided [O. maculifera Young, 1977, O. discoidula (Osborn, 1926), O. triplehorni Young, 1977, O. linnavuorii, and O. flavolineata]. The superficially similar genera Oragua and Aguana Melichar, 1926 are briefly compared. PMID- 27395682 TI - Ambaeolothrips: a new genus of Neotropical Aeolothripidae (Thysanoptera), with observations on the type-species from mango trees in Mexico. AB - Ambaeolothrips gen. n. is diagnosed for three Neotropical species: the type species romanruizi Ruiz-De la Cruz et al. comb. n. from Mexico, microstriatus Hood comb. n. from Panama, and pampeanus sp. n. from southern Brazil. Variation is discussed among character states that are used in the generic classification of the family Aeolothripidae, including segmentation of the antennae and maxillary palps, sculpture of the metanotum and presence of sternal discal setae. New field observations on the biology of romanruizi indicate that this species is phytophagous in flowers and on leaves, with no evidence of predation on the larvae of other thrips. PMID- 27395684 TI - Two new species of the genus Haplotropis Saussure, 1888 (Orthoptera, Acridoidea, Pamphagidae) from China. AB - Two new species of the genus Haplotropis Saussure, 1888 from China are described in this paper. The new species Haplotropis xiai sp. nov. is similar to Haplotropis brunneriana Saussure, 1888, but differs from latter by frontal ridge of male widened at median ocellus; tegmina narrower, cover 2/5 tympanum; cercus of male apical half part gently tapering; lower margin of epiphallus with high projection in the middle; anterior margin of pronotum in female with distinct acute angular in middle; length of subgenital plate shorter than width in female. The Haplotropis zhuoluensis sp. nov. is similar to Haplotropis xiai sp. nov., but differs from latter by anterior margin of pronotum reaching hind margin of eyes; length of temina is 1.6 times in male and 1.3 times in female of width; length of interspace shorter than narrowest in mesosternum of male; ancorae of epiphallus oblique inward distinctly, lower margin with high projection in the middle; length of subgenital plate longer than width in female. Type specimens are deposited in the College of Life Sciences, Hebei University, Baoding, China. PMID- 27395685 TI - The Sericothripinae genus Neohydatothrips (Thysanoptera, Thripidae) in India with description of two new species. AB - Two new species of Neohydatothrips are described from India, N. chandrai and N. plumeria. The former was collected on leaves of a hedge plant in northwest India, and the latter on flowers and leaves of Plumeria sp. in eastern India. A key to the seven species of Neohydatothrips recorded from India is also provided. Partial sequence data of mitochondrial cytochrome c oxidase (mtCOI) from the holotypes of each of these two new species were generated. PMID- 27395686 TI - Review of the genus Relaba (Hemiptera: Cicadellidae: Typhlocybinae: Alebrini) and description of two new species from Argentina. AB - The genus Relaba is reviewed, and two new species, R. forcipula n. sp. and R. globata n. sp. are added. Detailed morphological descriptions and illustrations of the new species, and a key to males of known species are provided. PMID- 27395687 TI - An annotated checklist of species in the family Lagenophryidae (Ciliophora, Oligohymenophorea, Peritrichia), With a brief review of their taxonomy, morphology, and biogeography. AB - The genera Lagenophrys Stein, 1852, Paralagenophrys Clamp, 1987, Clistolagenophrys Clamp, 1991, and Operculigera Kane, 1969 make up the family Lagenophryidae and, together, contain more than 80 species worldwide that live mainly as ectosymbionts of crustaceans. Lagenophryids are characterized by possession of a lorica, but the lorica aperture and the associated parts of the body differ between genera. Despite their widespread distribution, relatively few papers have been published on lagenophryids in recent years, and the present paper is intended to promote research on lagenophryids by providing an annotated checklist of all known species and a brief review of the family, including data of their geographic distribution and their hosts. PMID- 27395688 TI - Phylogenetic analysis of the genus Lensia (Cnidaria, Hydrozoa, Siphonophora), based on the species morphology. AB - Siphonophores are poorly studied despite their abundance and ecological importance in marine ecosystems. The genus Lensia Totton, 1932 contains the highest number of species within Siphonophora, but systematic studies of these organisms are scarce in the literature. This study presents a phylogenetic analysis for fifteen species of Lensia based on morphological data. The material for this study was obtained during two oceanographic campaigns made along the southeastern Brazilian coast. A total of twenty two characters of the anterior nectophore morphology were scored. The shortest trees were searched using parsimony (under different weighting regimes). All analyses provided the same topology: (M. kochi (D. dispar + D. bojani) (L. leloupi (L. havock (L. conoidea (L. subtilis; L. meteori; L. hardy; L. fowleri; (L. subtiloides (L. hotspur; L. cossack; L. campanella)); (L. multicristata (L. hunter (L. lelouveteau + L. grimaldii))). The monophyly of the genus Lensia is supported by the hydroecium measuring up to 1/4 the height of the nectosac. PMID- 27395689 TI - Taxonomy and natural history of Eutropis beddomei (Jerdon, 1870) (Reptilia: Scincidae), including a redescription of the holotype. AB - Euprepes beddomei was described by Jerdon (1870) from "Mysore" (Karnataka State, India). Simultaneously, Euprepes (Tiliqua) septemlineatus, which is morphologically similar to E. beddomei, was described by Blanford (1870) based on a single specimen collected from the Ganga River Valley, Southeast Berar, Madhya Pradesh, India. Smith (1935) synonymised the latter species (published in September, 1870) with Euprepes beddomei which in turn was published earlier (March, 1870). Jerdon's publication should therefore be given priority. A comprehensive comparison between the holotypes of the above two species confirms that E. septemlineatus is a junior synonym of E. beddomei. Based on morphological characters, Eutropis beddomei is here clearly identified and can be considered a widespread species in India and Sri Lanka. The original description of E. beddomei is very short and lacks a description containing most of the important diagnostic characters; hence, we hereby provide a comprehensive description of the species based on the examination of its holotype. PMID- 27395690 TI - Two new species of the deep-sea genus Parameiropsis (Copepoda: Harpacticoida) from the eastern central Pacific. AB - Two new species of Parameiropsis are herein described that were identified from the Korean Deep Ocean Study (KODOS) in the Clarion-Clipperton Fracture Zone, located in the eastern central Pacific. Parameiropsis kodosensis n. sp. is similar to P. magnus Ito, 1983 in two key respects: the presence of a distal seta on the syncoxa of the maxilliped, and the general features of its swimming legs. However, P. kodosensis can be differentiated from P. magnus by a higher length-to width ratio of the caudal ramus (2.5:1 and 1:1 respectively), the setal number on the exp-3 of P1, and the exp and benp of P5 are separated in P. kodosensis, while they are fused in P. magnus. Parameiropsis tetraspinosa n. sp. resembles P. peruanus Becker, 1974 in the absence of a fused seta in the outermost spine on the endopod of antenna and the general features of the swimming legs. However, P. tetraspinosa can be distinguished from P. peruanus by a higher length-to-width ratio of the caudal ramus (3.9:1 and 2.3:1 respectively), the presence of a distal seta on the syncoxa of the maxilliped, and by its medially fused P5. In this study full descriptions and a comparison with previously described species are provided. Additionally, a key to females of Parameiropsis species is given. PMID- 27395691 TI - Taxonomic study of the genus Cephalispa Malloch of Japan (Diptera: Muscidae). AB - Japanese species of the genus Cephalispa Malloch, 1935 are revised. Cephalispa kudoi sp. nov., C. okinawaensis sp. nov. and C. triquetra sp. nov. are described. Lispocephala xanthogaster (Shinonaga, 2003) is transferred to the genus. A key to Japanese species is provided. PMID- 27395692 TI - Lectotype designations and taxonomic corrections on Neotropical Scutelleridae described by G. Breddin (Hemiptera: Heteroptera). AB - Lectotypes are designated and documented for the following species and infrasubspecific taxa: Dystus villosus Breddin, 1904; Lobothyreus breviceps Breddin, 1914; Pachycoris torridus (Scopoli, 1772) var. laetissimus Breddin, 1906 (originally proposed as var. laetissima); P. torridus var. moestissimus Breddin, 1906 (originally proposed as var. moestissima); Polytes speculiger Breddin, 1914. The identities of the taxa in concern are clarified. The following new junior subjective synonyms are proposed: Pachycoris torridus (Scopoli, 1772) = P. torridus var. laetissimus Breddin, 1906, syn. nov., = P. torridus var. moestissimus Breddin, 1906, syn. nov. PMID- 27395693 TI - A new species of Abyssobrotula (Ophidiiformes, Ophidiidae) from the Kuril Kamchatka Trench. AB - A new abyssal ophidiid fish, Abyssobrotula hadropercularis, is described on the basis of two specimens caught at two stations at ca. 5000 meters of depth in the Kuril-Kamchatka Trench. The genus Abyssobrotula Nielsen, 1977 was previously known from the type species, A. galatheae Nielsen, 1977 of which 40-50 specimens now are reported from all oceans at depths greater than 2000 m. One of the specimens from the Puerto Rico Trench captured at 8370 m is still the deepest record for fishes. The new species differs from A. galatheae in having great number of pectoral-fin rays 14-15 (vs 10-11); greater eye diameter (1.2-1.3% SL vs 0.7-0.9% SL); larger prepelvic 14.0-14.5% SL (vs 10.5-12.5% SL) and preanal lengths 42.5% SL (vs 33.0-41.5% SL); opercular spine strongly developed (vs poorly developed); gill rakers on anterior arch robust and close-set (vs rakers thin and well separated). The description of A. hadropercularis makes it necessary to slightly modify the generic diagnosis. PMID- 27395694 TI - First description of the male and additional data on the female morphology of Aprostocetus rubi Graham (Hymenoptera: Chalcidoidea: Eulophidae). AB - The previously unknown male of Aprostocetus rubi Graham (Eulophidae: Tetrastichinae) was reared, together with females, from galls of the raspberry gall midge Lasioptera rubi (Schrank) (Diptera: Cecidomyiidae) collected in Central Poland. The male is described and illustrated for the first time, and additional information provided on the morphology of the female. PMID- 27395695 TI - Two new species of Milnesium (Tardigrada: Milnesiidae). AB - Two new species of Milnesium are described: Milnesium vorax sp. nov from Sicily and Milnesium tumanovi sp. nov. from Crimea. Milnesium vorax sp. nov. is uncoloured, with eye spots, smooth cuticle, wide buccal tube, stylet supports inserted on the buccal tube at almost 62 % of its length; claws with configuration [2-3]-[3-2]; accessory points present on the main branches. Milnesium tumanovi sp. nov. is also uncoloured, has eye spots, smooth cuticle, and wide buccal tube, but it has the stylet supports inserted on the buccal tube at about 52 % of its length, and claws with configuration [3-3]-[3-3]; the accessory points are present on the main branches. PMID- 27395696 TI - First molecular identification of Australapatemon burti (Miller, 1923) (Trematoda: Digenea: Strigeidae) from an intermediate host Radix labiata (Rossmaessler) (Gastropoda: Lymnaeidae) in Europe. AB - The strigeid digenean species Australapatemon burti (Miller, 1923) (Trematoda: Digenea: Strigeidae) was originally described from North America, but recorded in the Neotropical region (Drago et al. 2007; Hernandez-Mena et al. 2014; Blasco Costa et al. 2016) and in Central Europe (Faltynkova et al. 2007). In Europe, this species is rare, and there is not much information about its range (Faltynkova et al. 2007; Soldanova et al. 2012). Australapatemon burti has a complex life cycle with three larval stages, two of which (sporocyst and cercaria) use several species of freshwater snails, and the third stage (metacercaria) use non-specific host hirudineans (Dubois 1968; Davies & Ostrowski de Nunez 2012; Blasco-Costa et al. 2016). Adult flukes are parasitic in the intenstines of various waterfowl species, such as ducks and swans (Drago et al. 2007; Hernandez-Mena et al. 2014). Currently, the molecular data on this parasite species includes only nucleotide sequences of four adult specimens from Mexico (Hernandez-Mena et al. 2014). Their hosts were Mexican duck, Anas diazi Ridgway, American Wigeon, Anas americana Gmelin, Cinnamon Teal, Anas cyanoptera Vieillot, and Ruddy Duck, Oxyura jamaicensis (Gmelin) (Anserformes: Anatidae). PMID- 27395697 TI - One new species of the genus Nigrimacula Shi, Bian & Zhou, 2016 (Orthoptera: Meconematinae) from Sichuan, China. AB - The paper describels one new species, i.e. Nigrimacula sichuanensis Wang & Shi, sp. nov. from Sichuan, China, and provides photographs of morphological characters. The type material is deposited in the Museum of Hebei University. PMID- 27395698 TI - A new species of Austrothaumalea Tonnoir from Australia (Diptera: Thaumaleidae). AB - Austrothaumalea spiculata sp. nov. is described from Grampians National Park, in southwest Victoria (Australia). It is known only from the type series and is the second species of Thaumaleidae recorded from the Park. Illustrations of the male terminalia, as well as a distribution map, are provided. Phylogenetic affinities are hypothesized and an updated species identification key is offered. PMID- 27395699 TI - Margarita Metallinou (1985-2015). PMID- 27395700 TI - Taxonomy and morphology of species of the genus Squalus Linnaeus, 1758 from the Southwestern Atlantic Ocean (Chondrichthyes: Squaliformes: Squalidae). AB - Squalus is a genus of reportedly cosmopolitan shark species that have a high taxonomic complexity due to difficulties in their morphological differentiation; many of its species need revision. Currently, there are 26 valid species of Squalus, which have been divided into three species-groups according to overall morphological similarity, the S. acanthias, S. megalops, and S. mitsukurii groups. Loss of type specimens, propagation of erroneous identifications in the literature, and difficulties in obtaining representative series for comparison are secondary challenges that have impeded a global taxonomic revision of the genus. This problem applies clearly to species from the Southwestern Atlantic Ocean, including species that occur off Brazil. Following a current global tendency, a regional taxonomic revision of Squalus was conducted in order to investigate which species are valid in the Southwestern Atlantic Ocean and provide diagnostic morphological characters that can be efficiently used for identifying species. Comparative detailed analysis of external (e.g. morphometrics, dentition, and color pattern) and skeletal morphology (primarily meristic data, neurocrania and claspers) of specimens of Squalus from the region revealed four new species that are herein described (S. albicaudus sp. nov., S. bahiensis sp. nov., S. lobularis sp. nov., and S. quasimodo sp. nov.), as well as S. acanthias, which is redescribed from the region based on new material. Comparisons are offered based on examinations of congeneric species; this work is part of a global systematic revision of Squalus. PMID- 27395701 TI - Revision of the American species of the genus Prionus Geoffroy, 1762 (Coleoptera, Cerambycidae, Prioninae, Prionini). AB - A revision of the American species of Prionus Geoffroy, 1762 is presented. Prionus (Neopolyarthron) Semenov, 1899 and Prionus (Antennalia) Casey, 1912 are synonymized with Prionus Geoffroy, 1762. Homaesthesis LeConte, 1873 is considered a true subgenus of Prionus. Prionus (Homaesthesis) rhodocerus Linsley, 1957 and Prionus (Homaesthesis) linsleyi Hovore, 1981 are synonymized with Prionus simplex (Casey, 1912). Prionus beauvoisi Lameere, 1915 and Prionus (Neopolyarthron) debilis Casey, 1924 are synonymized with P. imbricornis (Linnaeus, 1767). Prionus (Neopolyarthron) townsendi Casey, 1912 and Prionus (Neopolyarthron) curticollis Casey, 1912 are synonymized with Prionus mexicanus Bates, 1884. Prionus batesi Lameere, 1920 is synonymized with Prionus aztecus Casey, 1912. Prionus hintoni Linsley, 1935 is synonymized with Prionus flohri Bates, 1884. Prionus (Antennalia) fissicornis parviceps Casey, 1912 is excluded as the synonym of Prionus fissicornis Haldeman, 1846 and instead synonymized with P. imbricornis (Linnaeus, 1767). Prionus (Prionus) validiceps Casey, 1912 is excluded from the synonymy of P. pocularis Dalman, 1817, and synonymized with P. (P.) californicus Motschulsky, 1845. Prionus (Prionus) tumidus Casey, 1912 is excluded from the synonymy of P. heroicus Semenov, 1907, and synonymized with P. (P.) californicus. The lectotype female and the paralectotype male of Prionus (Prionus) tristis are excluded from the synonym of P. (P.) heroicus and transferred to the synonym of P. (P.) californicus; the paralectotype female of P. (P.) tristis is maintained in the synonymy of P. (P.) heroicus. Prionus (Prionus) fontinalis Casey, 1914 is excluded from the synonymy of P. (P.) heroicus and synonymized with P. (P.) californicus. Prionus simplex is formally excluded from the Cerambycidae fauna of Oklahoma, USA. Comments on the page, plate, and figure of publication of Cerambyx laticollis Drury, 1773 are presented. Prionus (Trichoprionus) Fragoso & Monne, 1982 is considered a genus different from Prionus. Hypoprionus is designated as a replacement name for Prionellus Casey, 1924 and Cerambyx laticollis Drury, 1773 is designated as the type species. Comments on the type localities of Prionus emarginatus, Prionus palparis Say, 1824, and Prionus (Neopolyarthron) aztecus Casey, 1912 are presented. Prionus (Homaesthesis) integer sensu Linsley (1962) and Chemsak (1996) is described as P. (H.) geminus, new species. Comments on the date of publication of Prionus fissicornis Haldeman, 1846 are presented. Comments on the status of the syntypes of Cerambyx imbricornis Linnaeus, 1767 are also presented. Lectotype specimens for Prionus flohri Bates, 1884, Prionus (Prionus) tristis, and Prionus lecontei Lameere, 1912 are designated. Comments on the number of specimens used in the original description of Prionus californicus are presented, and a lectotype for this species is designated. New state records are presented for Prionus emarginatus Say, 1824; P. imbricornis (Linnaeus, 1767); P. aztecus Casey, 1912; P. poultoni Lameere, 1912; P. pocularis Dalman, 1817; and P. mexicanus Bates, 1884. PMID- 27395702 TI - Catalogue of the mite family Tydeidae (Acari: Prostigmata) with the world key to the species. AB - Members of the Tydeidae are cosmopolitan, soft-bodied, striated or reticulated mites that are reported to be mainly phytophages, mycophages, pollenophages, insect parasites or scavengers. This catalogue includes 328 species belonging to 30 genera, and their distributions and type habitat. Until now, Brachytydeus comprises the largest number of species with 200, followed by Tydeus, with 50 species, and Pretydeus and Pseudolorryia, with 12 species each. An updated list of the Tydeidae (Acari: Prostigmata), a world key to the species and data on the zoogeographical distribution of the species are presented. PMID- 27395703 TI - Taxonomic review on the subgenus Tripodura Townes (Diptera: Chironomidae: Polypedilum) from China with eleven new species and a supplementary world checklist. AB - The subgenus Tripodura Townes of Polypedilum Kieffer from China including 26 species is reviewed. Eleven new species, named P. (T.) absensilobum Zhang & Wang sp. n., P. (T.) apiculusetosum Zhang & Wang sp. n., P. (T.) arcuatum Zhang & Wang sp. n., P. (T.) bilamella Zhang & Wang sp. n., P. (T.) conghuaense Zhang & Wang sp. n., P. (T.) dengae Zhang & Wang sp. n., P. (T.) mengmanense Zhang & Wang sp. n., P. (T.) napahaiense Zhang & Wang sp. n., P. (T.) parallelum Zhang & Wang sp. n., P. (T.) pollicium Zhang & Wang sp. n. and P. (T.) trapezium Zhang & Wang sp. n. are described and illustrated based on male imagines. Three species, P. (T.) quadriguttatum Kieffer, P. (T.) unifascia (Tokunaga) and P. (T.) udominutum Niitsuma are firstly recorded in China. A key to known male imagines of Chinese species and an updated world checklist of subgenus Tripodura are presented. PMID- 27395704 TI - New taxa, new records and notes on Coleoxestia Aurivillius, 1912 (Coleoptera, Cerambycidae, Cerambycinae). AB - The following new records are reported: Coleoxestia julietae Galileo & Martins, 2006 (new department record in Bolivia; Peru, new country record); C. spinipennis spinipennis (Audinet-Serville, 1834) (Bolivia, new country record; French Guiana, new country record); C. nitida (Bates, 1872) (Bolivia, new country record); C. anthracina Martins & Monne, 2005 (Bolivia, new country record); C. glabripennis (Bates, 1870) (Peru, new country record; French Guiana, new country record); C. pubicornis (Gounelle, 1909) (Peru, new country record); C. rubromaculata (Gounelle, 1909) (Peru, new country record; French Guiana, new country record); C. rufosemivittata Tippmann, 1960 (Peru, new country record); C. illex (Gounelle, 1909) (Bolivia, new country record). Color pattern variation is reported for the first time in C. julietae and C. glabripennis (Bates, 1870). Presence of lateral spine on prothorax of Coleoxestia is reported for the first time in C. rufosemivittata Tippmann, 1960 and C. nitida. The male of C. spinifemorata Fragoso, 1993 is described. Two new species are described: C. weemsi from Trinidad and Tobago; C. bettellaorum from Bolivia. PMID- 27395705 TI - Studies in Australian Tettigoniidae: A review of the Australian katydids of the genus Goodangarkia (Tettigoniidae: Conocephalinae; Agraeciini; Liarina). AB - Six species in Goodangarkia are described. Information on the distribution. ecology and cytology of species is presented. An unusual characteristic of cranial stridulation of one species is noted. Cytological evidence suggests the chromosome complement of species are more basal than those from Africa for example. PMID- 27395706 TI - The first record of Baccharis L. (Asteraceae) as a host-plant genus for Nepticulidae (Lepidoptera), with description of new Stigmella species from South America. AB - We record the first Nepticulidae species found to feed on Baccharis L. (Asteraceae). Despite the high species richness of Baccharis in the Western Hemisphere, no nepticulid has ever been recorded feeding on Baccharis. In this paper we describe six new Stigmella Schrank species feeding on Baccharis: S. emarginatae Diskus & Stonis, sp. nov., S. bipartita Diskus & Stonis, sp. nov., S. tripartita Diskus & Stonis, sp. nov., S. latifoliae Remeikis, Diskus & Stonis, sp. nov., S. baccharicola Diskus & Stonis, sp. nov., and S. confertae Diskus & Stonis, sp. nov. The remaining two taxa are left unnamed. All taxa are illustrated with photographs of adults, their genitalia, and their leaf-mines. Additionally, leaf-mines on Baccharis salicifolia are documented. PMID- 27395707 TI - Oxyropsis ephippia, a New Hypoptopomatine Catfish (Siluriformes: Loricariidae) from Guyana. AB - Oxyropsis ephippia, a new species of loricariid catfish in the subfamily Hypoptopomatinae, is described from the Essequibo and Branco basins, Guyana. Based on the presence of a keel-like row of relatively enlarged odontodes on trunk median plates immediately above the lateral line canal, the new species is assigned to the genus Oxyropsis Eigenmann & Eigenmann 1889. It can be distinguished from its congeners by having the keel-like row on each median plate dominated by a single odontode (one closest to the posterior margin of the plate) conspicuously larger than preceding ones, and by having the sides of the trunk below the median series (approximately between median plates 7 to 12) shielded only by plates of the midventral series, with the exclusion of plates from the ventral series. The report of O. ephippia from the Essequibo is the first record of the genus in a river system that drains the north-central portion of the Guiana Shield into the Atlantic Ocean. PMID- 27395708 TI - The identity of the Brachyplatys species recently introduced to Panama, with a review of bionomics (Hemiptera: Heteroptera: Plataspidae). AB - A recent report of a population of Brachyplatys vahlii (Fabricius, 1787) (Hemiptera: Heteroptera: Plataspidae) introduced to Panama is considered as misidentification, the species in concern is recognized as B. subaeneus (Westwood, 1837). Syntypes of B. subaeneus and diagnostic characters of the species are illustrated, published information on its distribution, bionomics and economic importance is reviewed. Syntypes of B. vahlii are illustrated, taxonomic problems in connection with the species are highlighted. PMID- 27395709 TI - Contributions to the knowledge of North American tenebrionids of the subtribe Cylindrinotina (Coleoptera: Tenebrionidae: Helopini). AB - Three North American species of Helops are reassigned to the genus Nalassus: N. aereus (Germar, 1824), comb. n., N. californicus (Mannerheim, 1843), comb. n., N. convexulus (LeConte, 1861), comb. n. Current distributions as well as paleo distributions are discussed. A lectotype is designated for Helops californicus. PMID- 27395710 TI - New species of Pisionidens (Sigalionidae, Annelida) from Akumal, Mexico. AB - Pisionidens Aiyar & Alikuhni, 1943 is a genus of small scale-less annelids formerly belonging to the family 'Pisionidae', now synonymized with the scale worm family Sigalionidae. A new species from Akumal, Mexico, Pisionidens ixazaluohae n. sp., is herein described, including a genetic barcode, and diagnosed by parapodia from segment 8, males having a continuous line of midventral pores, and the presence of a single copulatory segment without parapodia. The new species differs in morphology from the three previously described species, including P. indica (Aiyar & Alikuhni, 1940), representing the only other species previously reported from the Caribbean Sea and Gulf of Mexico. A comparative table with a summary of the main taxonomic characters of all described species of the genus, including information on distribution, is provided. PMID- 27395711 TI - Revision of Ishigakia Uchida (Hymenoptera: Ichneumonidae: Acaenitinae) from Japan, with a new species having a close relative in South Africa. AB - Two Japanese species of the genus Ishigakia Uchida, 1928, i.e., the type species from Ryukyus, I. exetasea Uchida, and a new species from Honshu, I. albitarsa Ito & Maeto sp. nov., are (re-)described. Antennal tapping and oviposition behavior of female I. exetasea was observed on the stalks of Japanese silvergrass Miscanthus sinensis. The new species, I. albitarsa, has (presumably) close relatives from mainland China and, disjunctely, from South Africa. A key to the world species of Ishigakia is also provided. PMID- 27395712 TI - Three new species of the genus Lepidostoma Rambur (Lepidostomatidae: Trichoptera) from India. AB - Three new species of the genus Lepidostoma Rambur are described and illustrated from the Indian Himalaya: Lepidostoma trilobatum sp. nov., L. lidderwatense sp. nov., and L. sainii sp. nov., all belonging to the Lepidostoma ferox Branch. With these new additions, the genus Lepidostoma is now represented by 50 species in India and over 450 species globally. PMID- 27395713 TI - New record of the genus Peramphithoe Conlan & Bousfield, 1982 (Amphipoda: Ampithoidae) from Brazilian coast, with description of a new species. AB - A new species Peramphithoe conlanae sp. nov. is described from Todos os Santos Bay, Bahia, Northeast Brazil. The new species is characterized by the morphology of male gnathopod 1 coxa with anteroventral corner acute, palm transverse bearing a robust seta on the palmar corner and dactylus 2 * palm length, gnathopod 2 with propodus oval, palm extremely acute, concave and lacking processes or robust setae, pereopods 5 and 6 with merus and carpus inflated. This paper increases the number of described species in the genus to 22. It is the first record of the genus Peramphithoe from Brazilian waters. PMID- 27395714 TI - A new species of Ampithoe Leach, 1814 (Senticaudata, Ampithoidae) from Brazilian coast. AB - In this paper we describe a new species from Brazilian waters, Ampithoe suapensis sp. nov., from Pernambuco State, Brazil. This species is readily separated from its congeners by the following states of characters: mandible with palp slender, with 2 long setae on distal margin of article 3; gnathopod 2 propodus oval with palm densely setose, extremely acute and lacking ornamentation, peduncle of male uropod 1 with a blunt interramal process. Also, a key for the Ampithoe species found in Brazilian waters is provided. PMID- 27395715 TI - Fifteen new species of the spider genus Pholcus (Araneae: Pholcidae) from Southeast Asia. AB - Fifteen new species from six species groups of the genus Pholcus Walckenaer, 1805 are described from Southeast Asia: Pholcus hinsonensis sp. nov. (male & female, Thailand) and P. tharnlodensis sp. nov. (male & female, Thailand) from the P. bidentatus species group; P. kottawagamaensis sp. nov. (male & female, Sri Lanka) from the P. ethagala species group; P. cenranaensis sp. nov. (male & female, Indonesia) and P. krachensis sp. nov. (male, Thailand) from the P. gracillimus species group; P. anaiensis sp. nov. (male, Indonesia), P. ballarini sp. nov. (male & female, Thailand), P. gou sp. nov. (male & female, Myanmar), P. wan sp. nov. (male & female, Thailand) and P. zhuchuandiani sp. nov. (male & female, Indonesia) from the P. halabala species group; P. chiangmaiensis sp. nov. (male & female, Thailand) and P. taptaoensis sp. nov. (male & female, Thailand) from the P. quinquenotatus species group; P. kaebyaiensis sp. nov. (male & female, Thailand), P. musensis sp. nov. (male & female, Thailand) and P. songkhonensis sp. nov. (male & female, Thailand) from the P. yichengicus species group. PMID- 27395716 TI - Morphology of the immature female stages and the wax test of ten species of Ceroplastes (Hemiptera: Coccomorpha: Coccidae: Ceroplastinae) from Brazil. AB - This paper describes the development of the waxy test and the microscopic characters of the three female nymphal instars of Ceroplastes cirripediformis Comstock, C. diospyros Hempel, C. floridensis Comstock, C. flosculoides Matile Ferrero, C. formicarius Hempel, C. formosus Hempel, C. grandis Hempel, C. iheringi Cockerell, C. lucidus Hempel, and C. stellifer (Westwood). The discussion compares their morphology and divides the species into three groups according to the pattern of their dermal and wax characters. PMID- 27395717 TI - Southern Andean Stigmella sinuosa complex (Lepidoptera, Nepticulidae): unraveling problematic taxonomy with a pictorial key of adults? AB - On the basis of morphological studies of a collection sample from the southern Andes of Argentina and Chile, we describe and name two new species of Stigmella Schrank (Lepidoptera: Nepticulidae): S. sinuosa Remeikis & Stonis, sp. nov. and S. mevia Remeikis & Stonis, sp. nov. Other two new species are documented but left unnamed. All treated taxa belong to a newly designated S. sinuosa complex that belongs to the S. salicis group. The S. sinuosa complex contains cryptic species. We also discuss the differentiation of the species of the complex by using morphological characters. PMID- 27395718 TI - A new species of Zosime (Copepoda: Harpacticoida: Zosimeidae) from shallow subtidal habitats in Korea, with notes on the genus. AB - Zosime destituta sp. nov. is described from shallow subtidal habitats in the southern sea of Korea. The new species is similar to Z. valida Sars, 1919, but differs from it primarily by the lack of an inner seta on the third endopodal segment of the fourth swimming leg. Based on morphological comparison of female character states, the genus Zosime can be subdivided into three provisional groups, anneae-, incrassata-, and typica-group. These groups are distinguished from each other by differences in the antennule, antennary exopod, mandibular rami, armature of swimming legs, fifth leg, and caudal rami. In addition, Zosime incrassata bathybia Bodin, 1968 is removed from its synonymy with Z. incrassata Sars, 1910 and upgraded to species level. An amended key to all known species of Zosime Boeck, 1873 is given, along with a table of all major characters. The present study is the first report of the family Zosimeidae Seifried, 2003 from Korean waters. PMID- 27395719 TI - Type specimens of Sphecidae (Hymenoptera, Apoidea) in the Zoological Institute of the Russian Academy of Sciences in St. Petersburg. AB - The article contains a review of the type specimens of Sphecidae described by E. Eversmann, F. F. Morawitz, F. F. Kohl, V. V. Gussakovskij, V. L. Kazenas, A. S. Menke and Yu. Danilov, and deposited at the Zoological Institute of the Russian Academy of Sciences in St. Petersburg. Altogether 157 type specimens of 56 taxa were examined. Type specimens of Podalonia kozlovii (Kohl, 1906), whose depository was previously unknown, have been located. PMID- 27395720 TI - Taxonomic note of Oberea fuscipennis (Chevrolat, 1852) based on morphological and DNA barcode data (Coleoptera, Cerambycidae, Lamiinae). AB - Oberea fuscipennis (Chevrolat, 1852) species group is revised based on morphology and DNA barcode data. Oberea diversipes Pic, 1919 and O. infratestacea Pic, 1936 are restored from synonymy. The following two new synonymies are proposed: Oberea fuscipennis ssp. fairmairei Breuning, 1962 = Oberea diversipes Pic, 1919; and Oberea hanoiensis Pic, 1923 = O. fuscipennis (Chevrolat, 1852). PMID- 27395721 TI - The Yellow-green Bush-tanager is neither a bush-tanager nor a sparrow:
Molecular phylogenetics reveals that Chlorospingus flavovirens is a tanager (Aves: Passeriformes; Thraupidae). AB - Molecular phylogenetic analyses of the genus Chlorospingus (Aves: Emberizidae) indicate that the genus is not monophyletic because Chlorospingus flavovirens is actually a member of the tanager family (Thraupidae), in which its closest relatives are members of the genus Bangsia. We thus propose that C. flavovirens be transferred to Thraupidae and to the genus Bangsia. PMID- 27395722 TI - Two new species and key to six species of the genus Taipodisma Yin, Zheng & Yin, 2014 from Taiwan, China (Orthoptera, Acridoidea, Catantopidae, Podisminae). AB - Two new species of the genus Taipodisma Yin et al, 2014 from Taiwan, China are described in this paper. The new species Taipodisma viriditibia sp. nov. is similar to Taipodisma hsiehi Yin et al., 2014, it differs from the latter by antennae longer, length of a middle segment 4.0 times its width; interspace of mesosternum longer in male, the length 2.0 times the narrowest; lateral lobes of metasternum slightly separated in male; epiproct of male with longitudinal sulcus at base only and length of subgenital plate of female longer than width. The new species Taipodisma kaohsiungensis sp. nov. is similar to Taipodisma nigritibia Yin et al., 2014, it differs from the latter by prozona of pronotum 1.2 times metazona; length of interspace as long as the narrowest in mesosternum of male; hind tibia yellowish green on lower side and length of subgenital plate longer than width in female. The type specimens are deposited in the National Museum of Natural Science, Taichung, Taiwan, China and the Institute of Entomology, Taiwan University, Taibei, Taiwan, China, respectively. PMID- 27395723 TI - The advertisement call of Ameerega pulchripecta (Silverstone, 1976)(Anura, Dendrobatidae). AB - The name Ameerega picta was once used to denote a lineage of poison frogs (Dendrobatidae) distributed throughout most of the Amazon basin (Silverstone 1976); more recently, to describe a phenetic group involving at least 18 species, Lotters et al. (2007) pointed out that some of the lineages were indeed derived from the former A. picta. Among them, the nominal species with the widest distribution is A. hahneli (Haddad & Martins 1994; Twomey & Brown 2008), also an alleged complex of poorly defined species (Grant et al. 2006; Fouquet et al. 2007; Roberts et al. 2007). The mate-recognition signal, the advertisement call, was part of the evidence used to revalidate A. hahneli as a different species from A. picta. Although the advertisement call has been described for one or few individuals of other species in the group (Haddad & Martins 1994; Costa et al. 2006; Twomey & Brown 2008; Lotters et al. 2009), namely A. flavopicta, A. braccata and A. boehmei, and A. hahneli, we still lack a formal description for A. pulchripecta, the sister taxon of A. hahneli (Twomey & Brown 2008). Its call has been qualitatively described as similar to A. hahneli's call, but "deeper voiced" (Lotters et al. 2007). PMID- 27395724 TI - A new species of Tinodes (Trichoptera: Psychomyiidae) from Madagascar. AB - The genus Tinodes (Psychomyiidae) has a wide distribution in the Eastern Hemisphere with the richest species assemblages in the Oriental and southern parts of the Western Palearctic regions. In comparison with the species assemblages in those regions, diversity of the African species of this genus is relatively poor. A brief review of the 10 then-known Afrotropical species belonging to the genus Tinodes was published by Johanson & Olah (2007) together with descriptions of 14 new species. Some of these new species came from the Eastern African Arc of crystalline mountains, although 5 species have been found in Madagascar and the Comoros where no species of the genus Tinodes have been known previously. These new findings suggest continuing poor knowledge of the Afrotropical faunas where many species escaped descriptions until the beginning of the XXI century. PMID- 27395725 TI - Bottomless barrel-sponge species in the Indo-Pacific? AB - The use of nuclear markers, in addition to traditional mitochondrial markers, helps to clarify hidden patterns of genetic structure in natural populations (Palumbi & Baker, 1994). This is particularly evident among demosponges that possess slow mitochondrial evolutionary rates compared to Bilateria, where nuclear intron markers can aid in the understanding of shallow level phylogenetic relationships (Shearer et al., 2002). Ideally, these nuclear markers (i) are evolutionary well-conserved across different lineages, (ii) produce amplicons holding a number of sites with sufficient variability to answer the relevant phylogenetic question, (iii) derive from single copy genes (see review in Zhang & Hewitt, 2003). A popular method to amplify intron markers uses EPIC (Exon-Primed, Intron-Crossing) primers that anneal to the more conserved flanking exon regions and subsequently bridge the intron during amplification (Palumbi & Baker, 1994). PMID- 27395726 TI - A new species of Holocephalus Hope from Paraguay (Coleoptera: Scarabaeidae: Scarabaeinae: Dichotomiini s. str.). AB - It came to us from Svatopluk Pokorny a single Scarabaeinae specimen from Paraguay which we promptly diagnosed as belonging to the genus Holocephalus Hope, mainly due to the shape of first labial palpomere, head, cephalic carina, pronotum and other secondary charateristics (Smith & Genier 2001, Vaz-de-Mello et al. 2011). Comparisons with the diagnosis provided in the very fine and comprehensive revision of the genus (Smith & Genier 2001) and with specimens deposited at CEMT (Cuiaba-MT, Brazil) allowed us to confirm that this exemplar belongs to a new species of Holocephalus, which is described here. Besides providing illustrated description and diagnosis of the sixth discovered species of the genus, we differentiate it in a Holocephalus key adapted from Smith & Genier (2001) and also provide additional geographical records for other species in the genus. PMID- 27395727 TI - The Filistatidae in the Caribbean region, with a description of the new genus Antilloides, revision of the genus Filistatoides F. O. P.-Cambridge and notes on Kukulcania Lehtinen (Arachnida, Araneae). AB - A synopsis of Caribbean filistatid diversity is recorded herein. A new genus, Antilloides, is proposed for five new species exclusively found in the Antilles: A. abeli n. sp., A. cubitas n. sp., and A. mesoliticus n. sp. from Cuba; A. haitises n. sp. from the Dominican Republic; and A. zozo n. sp. from the U. S. Virgin Islands and Puerto Rico. The genus Filistatoides is revised and includes four species: the type species F. insignis F.O.P. Cambridge, which occurs only in Guatemala; the female is described here for the first time; F. polita Franganillo sp. reval., comb. nov., which occurs only in Cuba; F. xichu n. sp. described from Mexico; and F. milloti (Zapfe) which does not appear to belong to the genus based on morphological structures. Additionally, Kukulcania isolinae Alayon is synonymized with Kukulcania hibernalis (Hentz), and new records of its distribution are included for the Greater and Lesser Antilles. PMID- 27395728 TI - A new species of lithistid sponge hiding within the Isabella mirabilis species complex (Porifera: Demospongiae: Tetractinellida) from seamounts of the Norfolk Ridge. AB - A population level study of the lithistid ('rock') sponge, Isabella mirabilis, revealed a new species, Isabella tanoa sp. nov., living on five seamounts on the Norfolk Ridge, SW Pacific, and representing the third species to be discovered since the genus was first described in 2005. Comparisons between the three species showed significant differences in morphological characters that corresponded to differences in their respective CO1 barcoding sequences. Conversely, three of the four genotypes of Isabella mirabilis remain unresolved using morphological markers. PMID- 27395729 TI - Dragons in the mist: three new species of Pseudocalotes Fitzinger (Squamata: Agamidae) from the sky island archipelago of Peninsular Malaysia. AB - An integrative taxonomic analysis is used to delimit and describe three new species of Pseudocalotoes from the sky island archipelago of the Banjaran (=mountain range) Titiwangsa of Peninsular Malaysia. Pseudocalotes drogon sp. nov., from Fraser's Hill, Pahang is basal to the sister species P. larutensis from Bukit Larut, Perak in the Banjaran Bintang and the new species P. rhaegal sp. nov. from Cameron Highlands, Pahang. Pseudocalotes drogon sp. nov. is differentiated from all other species of Psuedocalotes by having the combination of a flat rostrum; seven postrostrals; an interparietal; 11 circumorbitals; five canthals; 7-10 superciliaries; one scale between the rostral and nasal; nine supralabials; eight infralabials; 10 postnasal-suborbital scales; four postmentals; five or six sublabials; five or six chinshields; 47 smooth, wide, gular scales; weak transverse gular and antehumeral folds; two enlarged scales between the ear and eye; enlarged upper and lower posttemporals; a single enlarged supratympanic; no enlarged postrictals; three large scales bordering the dorsal margin of the ear opening; large pretympanic scales; eight scales in the nuchal crest not separated by a gap; enlarged vertebral scales extending to the tip of the tail; keeled and non-plate-like scales on flanks; 51 midbody scales; midventrals smaller than dorsals; 19 subdigital lamellae on the fourth finger; 23 subdigital lamellae on the fourth toe; preaxial scales on third toe enlarged and spinose; subdigital lamellae not unicarinate; HW/HL 0.52; HL/SVL 0.31; no elbow or knee patches; and a male dewlap color of lime-green bearing a central yellow spot. Pseudocalotes rhaegal sp. nov. is differentiated from all other Psuedocalotes by having the combination of a convex rostrum; 6-8 postrostrals; an interparietal; nine or 10 circumorbitals; five canthals; 7-10 superciliaries; one or two scales between the rostral and nasal scales; eight or nine supralabials; seven or eight infralabials; 11 or 12 postnasal-suborbital scales; four postmentals; four or five chinshields; 40-45 smooth, wide, gular scales; no transverse gular fold; a weak antehumeral fold; three or four enlarged scales between the ear and eye; an enlarged upper and lower posttemporal; an enlarged supratympanic; no enlarged postrictals; no large scales bordering the upper margin of the ear opening or in the pretympanic region; 6-8 enlarged nuchal crest scales not separated by a gap; enlarged vertebral scales extending to the base of the tail; weakly keeled, non-plate-like scales on the flanks; 52-58 midbody scales; midventrals smaller than dorsals; 19-21 subdigital lamellae on the fourth finger; 22-26 subdigital lamellae on the fourth toe; preaxial scales on the third enlarged and rounded; subdigital lamellae not unicarinate; HW/HL 0.50-0.54; HL/SVL 0.28-0.30; no elbow or knee patches; and female dewlap color yellow bearing a purple base. The analyses also indicated that the new species, P. viserion sp. nov. from Genting Highlands, Pahang in the southern section of the Banjaran Titiwangsa is the sister species of P. flavigula from Cameron Highlands 121 km to the north and can be separated from all other species of Psuedocalotes by having the combination of three postrostrals; 10 circumorbitals; four or five canthals; 5-7 superciliaries; rostral and nasals in contact; supralabials contacting the nasal; six or seven supralabials; six or seven infralabials; two or three postmentals; 47 or 48 smooth, flat, gular scales; three chinshields; weak transverse gular and antehumeral folds; two enlarged scales between the ear and eye; an enlarged upper and lower posttemporal; an enlarged supratympanic; no enlarged postrictals; 7-9 nuchal crest scales lacking gaps and not extending beyond midbody; weakly keeled and plate-like scales on the flanks; 35-38 midbody scales; ventrals smaller than dorsals; 22 or 23 subdigital lamellae on the fourth finger; 26 or 27 subdigital lamellae on the fourth toe; preaxial scales on the third toe not modified; subdigital scales not unicarinate; HW/HL 0.62; no white marking below the eye; dewlap in males yellow; and no elbow or knee patches. Pseudocalotes rhaegal sp. nov. most likely occurs in syntopy with P. flavigula in Tanah Rata at Cameron Highlands and its discovery adds to a growing body of literature detailing the recent descriptions of several new, upland, closely related, sympatric species in Peninsular Malaysia. Another new population referred to here as Pseudocalotes sp. nov. from the Hala-Bala Wildlife Sanctuary, Betong District, Yala Province, Thailand is discussed. The discovery and description of these three new Pseudocalotes from the upland regions of Peninsular Malaysia continues to underscore the remarkably high herpetological diversity and ecological complexity in this sky island archipelago that is still underestimated, unappreciated, and unprotected. PMID- 27395730 TI - On the distribution of the genus Teius Merrem, 1820 (Reptilia: Squamata: Teiidae). AB - The lizard genus Teius is composed by three species: Teius teyou, T. oculatus, and T. suquiensis and is distributed in South America, east of Andes. Teius teyou and T. oculatus have wide parapatric distributions with contact zones. Teius suquiensis is present in a small range along a sympatric area of the former species. In this work we analyze the distribution of the three species of Teius across its whole geographic range, examining its relationships with climatic parameters. We based our analysis on specimens in collections and literature records. Our analysis shows that the genus Teius is distributed from central Bolivia southwards to north of Rio Negro Province in northern Patagonia, Argentina. Teius teyou reaches the northernmost range limit of the genus whereas T. oculatus occupies the southernmost limit. Teius oculatus is related to open and moist environments whereas T. teyou is more adapted to xeric and forested areas. Teius suquiensis is present in xerophytic areas of Dry Chaco and Espinal. Climatic factors in the distribution of the distribution of the two widespread species show marked differences and seasonality. PMID- 27395731 TI - Rhipidia crane flies (Diptera: Limoniidae) from Korea. AB - Korean species of the crane fly genus Rhipidia Meigen, 1818 (Diptera: Limoniidae), are taxonomically revised. Rhipidia (Rhipidia) serena, new species, is described and figured. Rhipidia (R.) longa Zhang, Li, Yang, 2014, R. (R.) maculata Meigen, 1818 and R. (R.) sejuga Zhang, Li, Yang, 2014 are recorded for the first time in Korea. Previously known species, Rhipidia (R.) septentrionis Alexander, 1913 is redescribed and illustrated. Identification key for all Korean Rhipidia species is given. Most antennae, wings, male and female terminalia of all species are illustrated for the first time. PMID- 27395732 TI - Venezuelan geckos (Gekkonidae, Phyllodactylidae, Sphaerodactylidae) in the collection of the Universidad de Concepcion in Chile, with description of the type series of Gonatodes ligiae and Gonatodes petersi (Sphaerodactylidae). AB - Herein we catalogue all geckos (Gekkonidae, Phyllodactylidae and Sphaerodactylidae) collected by Roberto Donoso-Barros in Venezuela between 1963 and 1964, deposited in the Universidad de Concepcion in Chile. Donoso-Barros did not provide detailed descriptions of two species of Gonatodes named by him, despite both being valid species. We take the opportunity to do so and the type series of Gonatodes ligiae and G. petersi are described for the first time. We also present images in life of all species collected by Donoso-Barros in Venezuela. PMID- 27395733 TI - First molecular verification of Dixonius vietnamensis Das, 2004 (Squamata: Gekkonidae) with the description of a new species from Vinh Cuu Nature Reserve, Dong Nai Province, Vietnam. AB - Based on near-topotypic specimens of Dixonius vietnamensis from Khanh Hoa Province in southern Vietnam genetic analyses showed that the recently described D. taoi is sister to D. vietnamensis and several separate forms exist which previously have been misidentified as D. vietnamensis and D. siamensis. The Dixonius population from Vinh Cuu Nature Reserve, Dong Nai Province, Vietnam, represents an undescribed species. Dixonius minhlei sp. nov. can be distinguished from its congeners based on the following diagnostic characters: small size (up to 47.5 mm SVL); 7-9 supralabials; 14-15 rows of keeled tubercles on dorsum; 20 23 ventral scale rows; 7 or 8 precloacal pores in males; a canthal stripe running from rostrum through the eye and terminating at back of head; lateral second pair of postmentals maximum one quarter the size of first pair; dorsum olive gray with more or less discernible brownish olive blotches. This is the sixth species of Dixonius known to occur in Vietnam. PMID- 27395734 TI - Petrosaltator gen. nov., a new genus replacement for the North African sengi Elephantulus rozeti (Macroscelidea; Macroscelididae). AB - In 2003, a molecular phylogeny was published that examined the role of the Sahara Desert as a vicariant event in the evolution of sengis (also known as elephant shrews.) The phylogeny included a single sample from the North African sengi, Elephantulus rozeti (Duvernoy, 1833), which was found to be more closely related to the sengi genus Petrodromus Peters, 1846 than to other Elephantulus. Here we independently test the monophyly of Elephantulus using an additional specimen of E. rozeti and similar phylogenetic analyses, and discuss additional morphological and behavioral data that support the phylogeny. We propose a revised taxonomy that reflects the current paraphyly of Elephantulus and the sister relationship of E. rozeti and Petrodromus, including a new genus name for the North African sengi, Petrosaltator rozeti gen. nov., nov. comb. We additionally define two tribes within the subfamily Macroscelidinae, the Macroscelidini (including Macroscelides, Petrodromus, and Petrosaltator), and the Elephantulini (including all other members of Elephantulus). PMID- 27395735 TI - Psilorhynchus tysoni, a new species of torrent minnow from the Salween River drainage, western Thailand (Teleostei: Psilorhynchidae). AB - Psilorhynchus tysoni, new species, is described on the basis of 10 specimens, 23.3-53.8 mm SL from the Mae Nam Moei and Hue Mae Song Rivers, in the Salween River drainage in western Thailand. It belongs to the P. nudithoracicus species group and can be distinguished from other members of this group by a combination of characters, including features of body and fin coloration, head shape, and caudal fin-ray, vertebrae, and cephalic lateral-line canal pore counts. Phylogenetic analyses of a mitochondrial DNA data set (comprising 642 bp of cytochrome c oxidase subunit 1 and 1140 bp of cytochrome b) for 12 species of Psilorhynchus and one outgroup taxon resulted in phylogenetic hypotheses in which P. tysoni is a member of a clade equivalent to the P. nudithoracicus species group. Within this group P. tysoni is placed as the sister taxon of a putatively undescribed species of Psilorhynchus from Myanmar. PMID- 27395736 TI - Electrolichas circumbalticus gen. et sp. nov. (Coleoptera: Byrrhoidea: Ptilodactylidae) from Baltic amber, the first anchytarsine toed-winged beetle described from Europe. AB - A new genus and species of Ptilodactylidae, Electrolichas circumbalticus gen. et sp. nov., the first fossil representative of the subfamily Anchytarsinae, is described from Baltic amber. This Eocene beetle can be distinguished from the extant genera of Anchytarsinae by the combination of the following characters: labrum transverse, terminal segment of maxillary palps cylindrical, antennae with non-articulated rami, basal pronotal margin only very finely crenulate, lacking a median denticle, anterior margin of scutellum not excised medially, elytra not striate, tarsi not pseudotetramerous, proportional lengths: 1.5: 1.2: 1.2: 1.1: 1.5, flashy pads on apex of first tarsomere as well as on tarsomeres 2-4. A list of the extant species of Anchytarsinae is provided. Both hitherto described fossil ptilodactylid genera are briefly discussed. PMID- 27395737 TI - RANDY J. MERCURIO (2016) Resurrection of Scolopendra longipes Wood and Scolopendra cubensis Saussure from synonymy with Scolopendra alternans Leach (Chilopoda, Scolopendromorpha, Scolopendridae): an enigmatic species-group needing phylogeographic analysis, with an overview on the origin and distribution of centipedes in the Caribbean region. Zootaxa, 4111(1): 001-020. PMID- 27395738 TI - Lenticellaria and Hillerella, new kraussinoid genera (Kraussinoidea, Brachiopoda) from Indo-Pacific and Red Sea waters: evolution in the subfamily Megerliinae. AB - Two new kraussinid brachiopod genera, namely Lenticellaria gen. nov. and Hillerella gen. nov. are described from Pacific waters in the sub-equatorial zone in the Indonesian Archipelago, from Indian Ocean waters in Madagascar and from Red Sea waters in Egypt (Gulf of Aqaba) and Sudan. This fills the equatorial gap in the distribution of the superfamily Kraussinoidea, known from higher latitudes in both hemispheres. The micromorphic new material described is an excellent example of homeomorphy in brachiopods. It also provides new information on the distribution of the genus Megerlia sensu stricto and illustrates subtle variations in the evolutionary process of the reduced brachidium in Kraussinoidea. PMID- 27395739 TI - Taxonomic study of the genus Promalactis Meyrick (Lepidoptera, Oecophoridae) from Hainan Island, China (II). AB - Ten species of the genus Promalactis Meyrick, 1908 are treated from Hainan Island, China. Eight species are described as new: P. falciprocessa sp. nov.; P. bilobulata sp. nov.; P. longivalvaris sp. nov.; P. pugnivalvata sp. nov.; P. termelliptica sp. nov.; P. gladiata sp. nov.; P. lucida sp. nov. and P. latitaeniata sp. nov.; the male of P. caperatiella Kim et Park, 2014 and the female of P. clavata Du, Li et Wang, 2011 are reported for the first time in science; and P. caperatiella Kim et Park, 2014 is newly recorded in China. Images of adults and genitalia are provided. PMID- 27395740 TI - A new species of Metapelopia Silva, Oliveira & Trivinho-Strixino (Diptera: Chironomidae) from Peru. AB - A new species of the monotypic genus Metapelopia is described and illustrated based on all life stages. Adults of the Metapelopia peruensis sp. n. can be easily distinguished from those of M. corbii by the color pattern of the legs and abdomen. Larvae and pupae were collected associated with algae accumulated on rocks. PMID- 27395741 TI - A review of scuttle fly genera of Israel (Diptera: Phoridae), with new records and an identification key. AB - A brief review of Israeli scuttle flies is given. The following genera are new records for the country: Arabiphora, Billotia, Chonocephalus, Menozziola, Phalacrotophora, Pseudacteon, Psyllomyia, and Puliciphora. Eighteen species Arabiphora tenuifemorata, Chonocephalus depressus, Conicera floricola, Conicera similis, Gymnophora integralis, Gymnophora perpropinqua, Megaselia scalaris, Megaselia stigmatica, Menozziola schmitzi, Metopina formicomendicula, Phalacrotophora beuki, Phalacrotophora fasciata, Phora limpida, Phora tincta, Psyllomyia braunsi, Puliciphora rufipes, Spiniphora bergenstammi, and Tubicera lichtwardi-are added to the list of 56 phorid species previously known from Israel. Two species, Conicera similis and Megaselia scalaris, are recorded in association with the summer truffle Tuber aestivum commercially grown in northern Israel. The status of the Afrotropical Phora congolensis Beyer, 1965 is designated as nomen dubium. A lapsius calami, which led to an erroneous generic attribution of Metopina braueri in the paper on Israeli Metopina (Mostovski, 2016), is noted here. An identification key to the Israeli genera of scuttle flies, as well as notes on recognition and/or biology of individual species, are provided. PMID- 27395742 TI - A new species of the genus Melita (Amphipoda, Hadzioidea, Melitidae) from anchialine pool on the Cozumel Island, NE Caribbean Sea. AB - A new species of genus Melita collected from anchialine pool (Cenote Aerolito) on Cozumel Island is described. Distinctive characters of male of the new species include an accessory flagellum 4-articulate; palm of gnathopod 2 with long setae; urosomite 2 with two robust setae on right side, and one on left. Female of the new species differs by coxa 6 without lateral ridge at base of hook, and anteroventral angle without stridulating ridges on anteroventral process; gnathopods 1-2 covered with long setae on articles 5-6. The main morphological differences between males of Melita species recorded previously for the Gulf of Mexico and the Caribbean Sea and the new species are also given. PMID- 27395743 TI - All stages of the Palaearctic predaceous midge Palpomyia schmidti Goetghebuer, 1934 (Diptera: Ceratopogonidae). AB - All stages and the ecology of the Southern Palaearctic Palpomyia schmidti collected from the vicinity of the saline Lake Elton in Russia are described and illustrated. The morphology of larvae and pupae as well as the detailed ecology of the larvae are described for the first time. P. schmidti is a halobiontic biting midge, widely distributed in the steppes and deserts of the Palaearctic region. It is proposed that the Palpomyia schmidti group should include five Holarctic species. P. downesi Grogan & Wirth, 1979 from north-western North America is recognized as a new junior synonym of the Eastern Palaearctic P. tuvae Remm, 1972. New synonymy. PMID- 27395744 TI - A first record of Cretaceous aphids (Hemiptera, Sternorrhyncha, Aphidomorpha) in Australia, from the Lower Cretaceous Koonwarra Fossil Bed, Victoria. AB - This paper describes the first species of aphid from the Lower Cretaceous Koonwarra Fossil Bed of the Gippsland Basin, southeastern Victoria, Australia. This aphid, herein named Koonwarraphis rotundafrons gen. & sp. nov., is assigned to the cosmopolitan Cretaceous superfamily Tajmyraphidoidea, which has been previously described from the Lebanese, Taimyrian, Canadian, Myanmar (Burmese), and Spanish ambers. Koonwarraphis rotundafrons is the first aphid recorded from the eastern Gondwanan landmass during the Cretaceous, and represents the only tajmyraphidoid preserved as a compression fossil, rather than as an amber inclusion. Due to the nature of the fossil's preservation, Koonwarraphis cannot be firmly placed in any of the described tajmyraphidoid families; however, all observable morphological features suggest that the genus is broadly typical of the superfamily and Cretaceous aphids in general. Koonwarraphis' shortened rostrum, a feature also seen in other tajmyraphidoids, suggests an association with the more herbaceous aspects of the Early Cretaceous Victorian flora. Considering the modern aphid preference for angiosperm plants, it is possible that this aphid was living upon the herbaceous early angiosperms recorded previously from the Koonwarra macrofloral assemblage. PMID- 27395745 TI - The Neotropical species of Atractodes (Hymenoptera, Ichneumonidae, Cryptinae), I: the A. propodeator and A. altoandinus species-groups. AB - The Neotropical species of the cryptine genus Atractodes are studied, and four species-groups are proposed. In this paper, A. altoandinus and A. propodeator species-groups are diagnosed. The former species-group occurs from southern Mexico to Brazil and includes some of the largest Atractodes species ever found, all possessing a strongly sloped propodeum; the latter species-group is only known from the Chilean Andes and includes one of the smallest species of Atractodes, characterised by a very short and curved tergite I and short first flagellomere. Four species, A. altoandinus, A. propodeator, A. reijoi and A. verapacensis are described as new. An illustrated identification key to all species-groups and to species of the A. propodeator species-group is provided. PMID- 27395747 TI - Two new species of the genus Centromacronema Ulmer 1905 (Hydropsychidae: Macronematinae) from Brazil. AB - Centromacronema is an endemic genus from the Neotropics, with distribution ranging from Mexico to southern Brazil. The genus comprises 15 described species, but only two of them have been recorded in Brazil: Centromacronema auripenne (Rambur 1842) and C. obscurum (Ulmer 1905). Two new species are herein described and illustrated from Brazil, C. pioneira n. sp. from Serra da Jiboia, Bahia state, including the first description of a female for the genus, and C. poyanawa n. sp. from Serra do Divisor, Acre state. PMID- 27395746 TI - Timeless standards for species delimitation. AB - Recently a new species of bombyliid fly, Marleyimyia xylocopae, was described by Marshall & Evenhuis (2015) based on two photographs taken during fieldwork in the Republic of South Africa. This species has no preserved holotype. The paper generated some buzz, especially among dipterists, because in most cases photographs taken in the field provide insufficient information for properly diagnosing and documenting species of Diptera. PMID- 27395748 TI - Taxonomic review of the genus Isometopus (Hemiptera: Miridae: Isometopinae) from the Korean Peninsula, with description of a new species. AB - The genus Isometopus is reviewed from the Korean Peninsula with a new species: I. jejuensis sp. nov. I. japonicus Hasegawa, 1946 is also reported from South Korea for the first time. Genital structures of male and female of I. japonicus are illustrated and described for the first time. Last instar of I. japonicas is also described. Biological notes such as host plants and morphological characters are provided with the photographs and illustrations. A key to the Korean Isometopus species is also provided. PMID- 27395749 TI - A redescription of the monotypic felt scale insect genus Pedroniopsis Green (Hemiptera: Coccomorpha: Eriococcidae) from India and Burma. AB - Here we redescribe the felt scale genus Pedroniopsis Green and its type species Pedroniopsis beesoni Green for the first time since it was described 90 years ago. We consider that the genus belongs to the family Eriococcidae as presently understood but realise that the family may not be monophyletic. The species was collected in crevices and pits on the bark of Shorea robusta (Dipterocarpaceae) from Odisha State, India, which is its only known locality in India. We also record the species from Burma (Myanmar) for the first time living in galls on Dipterocarpus tuberculatus (Dipterocarpaceae) and, therefore, the species may have a wider distribution but has not been observed because of its cryptic habit. The adult females of the genus and species have some unusual features such as truncate-conical marginal and dorsal setae that are mostly bifid at the tip. We suggest that the genus may be similar in some respects to the genus Sangicoccus Reyne known from farther east in southern Asia. PMID- 27395751 TI - Development of a six-factor questionnaire for use in weight management counseling. AB - OBJECTIVE: To develop and validate a new 6 factor questionnaire (6-FQ) that identifies unhealthful behavioral, cognitive and affective lifestyle pattern factors among a large sample of adults who are overweight or obese. METHODS: Based on a previously developed 53-item lifestyle patterns questionnaire completed by 10,000 subjects, a new 6-FQ was developed and validated by using two prospective subject groups (n=640) with combined mean age of 43+/-11.4years and BMI 33.8+/-9.1kg/m2. RESULTS: An exploratory factor analysis and multidimensional scaling were conducted that identified 6 distinct factors with excellent psychometric properties. Cronbach's internal consistency reliability estimates ranged from 0.76 to 0.85. The prevalence rates and odds ratios of the factors are generally and directly related with increasing BMI categories. The 6-FQ is highly correlated with multiple subscales from the co-administered IWQOL-Lite questionnaire. CONCLUSIONS: The 6-FQ is a 27-item self-administered instrument with excellent psychometric properties that measures patients' lifestyle pattern factors. PRACTICE IMPLICATIONS: The 6-FQ is a convenient, short, self administered instrument that has potential to target patients' self-identified lifestyle patterns related to body weight, and should allow clinicians to efficiently and effectively counsel patients on targeted treatment recommendations. PMID- 27395750 TI - Does physician communication style impact patient report of decision quality for breast cancer treatment? AB - OBJECTIVE: Provider communication that supports patient autonomy has been associated with numerous positive patient outcomes. However, to date, no research has examined the relationship between perceived provider communication style and patient-assessed decision quality in breast cancer. METHODS: Using a population based sample of women with localized breast cancer, we assessed patient perceptions of autonomy-supportive communication from their surgeons and medical oncologists, as well as patient-reported decision quality. We used multivariable linear regression to examine the association between autonomy-supportive communication and subjective decision quality for surgery and chemotherapy decisions, controlling for sociodemographic and clinical factors, as well as patient-reported communication preference (non-directive or directive). RESULTS: Among the 1690 women included in the overall sample, patient-reported decision quality scores were positively associated with higher levels of perceived autonomy-supportive communication from surgeons (beta=0.30; p<0.001) and medical oncologists (beta=0.26; p<0.001). Patient communication style preference moderated the association between physician communication style received and perceived decision quality. CONCLUSION: Autonomy-supportive communication by physicians was associated with higher subjective decision quality among women with localized breast cancer. These results support future efforts to design interventions that enhance autonomy-supportive communication. PRACTICE IMPLICATIONS: Autonomy-supportive communication by cancer doctors can improve patients' perceived decision quality. PMID- 27395752 TI - Neonatal exposure to SERMs disrupts neuroendocrine development and postnatal reproductive function through alteration of hypothalamic kisspeptin neurons in female rats. AB - Selective estrogen receptor modulators (SERMs) are a class of therapeutic chemicals which present tissue-specific estrogen receptor modulating activity. Neonatal exposure to SERMs has been reported to adversely affect central nervous system development, however, mechanism and involvement of hypothalamic kisspeptin neurone in this impairment remains undetermined. To clarify this uncertainty, neonates from female Donryu rats were subcutaneously injected with raloxifene (RLX) at 0.1, 1, and 10mg/kg or tamoxifen (TMX) at 10mg/kg on postnatal day 0, and then hypothalamic KiSS1 mRNA expression and gonadotropin levels were investigated during young adulthood and estrous cycling was monitored until middle age. Treatment with RLX or TMX at 10mg/kg significantly depressed luteinizing hormone surge levels and KiSS1 mRNA expression in the anteroventral periventricular nucleus (AVPV), the control center of estrous cyclicity. The 10mg/kg TMX group also showed decreased levels of follicle-stimulating hormone and KiSS1 mRNA expression in the arcuate nucleus (ARC). Early cessation of normal estrous cycling was observed in the 10mg/kg RLX group, while the estrous cycle in the 10mg/kg TMX group had ceased by the start of the analysis. The same dose of tamoxifen or raloxifene had either weak-estrogenic or anti-estrogenic activity on the uterus, respectively; however, treatment in adulthood with both SERMs did not affect KiSS1 mRNA expression in either the AVPV or ARC in the present study. These results indicate that neonatal exposure to SERMs could disrupt neuroendocrine development and postnatal reproductive function through the alteration of kisspeptin neurons. PMID- 27395753 TI - Comparison of corneal topographic measurements and high order aberrations in keratoconus and normal eyes. AB - PURPOSE: The aim of this report was to compare corneal topographic measurements and anterior high order corneal aberrations in eyes with keratoconus and normal eyes by using Scheimpflug-Placido topography. METHODS: Eighty cases diagnosed with mild (group 1), moderate (group 2), and advanced (group 3) stage keratoconus (KC) according to Amsler-Krumeich Classification and 81 healthy (control group) cases were retrospectively examined. The mean keratometric measurements (as both diopters (Kavg) and mm values (mmavg)), central corneal thickness values (CCT), high order aberration (HOA), total wavefront aberration (TWA), coma, trefoil, and spherical aberration measurements were performed using Sirius topography equipment. The topographic values were compared between the groups. RESULTS: There were 25 cases in group 1 KC (15.5%), 34 cases in group 2 KC (21.1%), 21 cases in group 3 KC (13.1%), and 81 cases (50.3%) in the control group. In terms of mean age and gender distributions, there was no statistically significant difference between the groups (p>0.05). However, there was significant difference between the groups in terms of Kavg, CCT, HOA, TWA, coma, trefoil, and spherical aberration values (p<0.01). Mean HOA, TWA, coma, trefoil, and spherical aberration values were observed to increase with the severity of KC disease. CONCLUSIONS: Anterior high order corneal aberrations were significantly increased in eyes with moderate and advanced keratoconus. Anterior high order corneal aberration measurements are a useful tool to guide the physician in diagnosis and classification of keratoconus. PMID- 27395754 TI - Numerical simulations to assess the tracer dilution method for measurement of landfill methane emissions. AB - Landfills are a significant contributor to anthropogenic methane emissions, but measuring these emissions can be challenging. This work uses numerical simulations to assess the accuracy of the tracer dilution method, which is used to estimate landfill emissions. Atmospheric dispersion simulations with the Weather Research and Forecast model (WRF) are run over Sandtown Landfill in Delaware, USA, using observation data to validate the meteorological model output. A steady landfill methane emissions rate is used in the model, and methane and tracer gas concentrations are collected along various transects downwind from the landfill for use in the tracer dilution method. The calculated methane emissions are compared to the methane emissions rate used in the model to find the percent error of the tracer dilution method for each simulation. The roles of different factors are examined: measurement distance from the landfill, transect angle relative to the wind direction, speed of the transect vehicle, tracer placement relative to the hot spot of methane emissions, complexity of topography, and wind direction. Results show that percent error generally decreases with distance from the landfill, where the tracer and methane plumes become well mixed. Tracer placement has the largest effect on percent error, and topography and wind direction both have significant effects, with measurement errors ranging from -12% to 42% over all simulations. Transect angle and transect speed have small to negligible effects on the accuracy of the tracer dilution method. These tracer dilution method simulations provide insight into measurement errors that might occur in the field, enhance understanding of the method's limitations, and aid interpretation of field data. PMID- 27395755 TI - Are scarce metals in cars functionally recycled? AB - Improved recycling of end-of-life vehicles (ELVs) may serve as an important strategy to address resource security risks related to increased global demand for scarce metals. However, in-depth knowledge of the magnitude and fate of such metals entering ELV recycling is lacking. This paper quantifies input of 25 scarce metals to Swedish ELV recycling, and estimates the extent to which they are recycled to material streams where their metal properties are utilised, i.e. are functionally recycled. Methodologically, scarce metals are mapped to main types of applications within newly produced Swedish car models and subsequently, material flow analysis of ELV waste streams is used as basis for identifying pathways of these applications and assessing whether contained metals are functionally recycled. Results indicate that, of the scarce metals, only platinum may be functionally recycled in its main application. Cobalt, gold, manganese, molybdenum, palladium, rhodium and silver may be functionally recycled depending on application and pathways taken. For remaining 17 metals, functional recycling is absent. Consequently, despite high overall ELV recycling rates of materials in general, there is considerable risk of losing ELV scarce metals to carrier metals, construction materials, backfilling materials and landfills. Given differences in the application of metals and identified pathways, prospects for increasing functional recycling are discussed. PMID- 27395756 TI - On the value of electrical resistivity tomography for monitoring leachate injection in solid state anaerobic digestion plants at farm scale. AB - Agricultural waste is a valuable resource for solid state anaerobic digestion (SSAD) thanks to its high solid content (>15%). Batch mode SSAD with leachate recirculation is particularly appropriate for such substrates. However, for successful degradation, the leachate must be evenly distributed through the substrate to improve its moisture content. To study the distribution of leachate in agricultural waste, electrical resistivity tomography (ERT) was performed. First, laboratory-scale experiments were conducted to check the reliability of this method to monitor infiltration of the leachate throughout the solid. Two representative mixtures of agricultural wastes were prepared: a "winter" mixture, with cattle manure, and a "summer" mixture, with cattle manure, wheat straw and hay. The influence of density and water content on electrical resistivity variations was assessed in the two mixtures. An increase in density was found to lead to a decrease in electrical resistivity: at the initial water content, resistivity decreased from 109.7 to 19.5Omega.m in the summer mixture and from 9.8 to 2.7Omega.m in the "winter" mixture with a respective increased in density of 0.134-0.269, and 0.311-0.577. Similarly, resistivity decreased with an increase in water content: for low densities, resistivity dropped from 109.7 to 7.1Omega.m and 9.8 to 4.0Omega.m with an increase in water content from 64 to 90w% and 74 to 93w% for "summer" and "winter" mixtures respectively. Second, a time-lapse ERT was performed in a farm-scale SSAD plant to monitor leachate infiltration. Results revealed very heterogeneous distribution of the leachate in the waste, with two particularly moist areas around the leachate injection holes. However, ERT was successfully applied in the SSAD plant, and produced a reliable 3D map of leachate infiltration. PMID- 27395757 TI - Segmental trunk and head dynamics during frontal plane tilt stimuli in healthy sitting adults. AB - A more detailed understanding of trunk behavior during upright sitting is needed to create a foundation to address functional posture impairments. Therefore, we characterized the dynamics of the trunk and head during perturbed sitting. A three-link inverted pendulum model of head and trunk segments was used to analyze kinematics of eight healthy sitting adults. Magnetic sensors were placed at the head and two locations of the trunk (C7 and T7). Six surface tilt stimuli (two spontaneous sway tests [no surface stimulus; eyes open, EO/eyes closed, EC] and four tests with continuous pseudorandom surface tilts [2 peak-to peak amplitudes of 2 degrees or 8 degrees ; EO/EC]) were applied in the frontal plane. We used frequency-response functions (FRFs) to analyze sway across ~0.045-3Hz and found systematic differences in sway dynamics across segments. Superior segments exhibited larger fluctuations in gain and phase values across frequencies. FRF gains in superior segments were attenuated compared to other segments only at low frequencies but were larger at the higher frequencies. We also tested the influence of stimulus amplitude and visual availability on FRFs. Across all segments, increasing stimulus amplitude and visual availability (EO) resulted in lower gains, however, these effects were most prominent in superior segments. These changes in gain were likely influenced by changes in sensory reliance across test conditions. In conclusion, these results provide a benchmark for future comparisons to segmental responses from individuals with impaired trunk control. We suggest that a frequency-based approach provides detail needed to characterize multi-segment dynamics related to sensorimotor control. PMID- 27395758 TI - Validity of parameters in static linear testing of flexor tendon repair. AB - To study the biomechanical properties of flexor tendon repairs, static tensile testing is commonly used because of its simplicity. However, cyclic testing resembles the physiological loading more closely. The aim of the present study is to assess how the biomechanical competence of repaired flexor tendons under cyclic testing relates to specific parameters derived from static tensile testing. Twenty repaired porcine flexor tendons were subjected to static tensile testing. Additional 35 specimens were tested cyclically with randomly assigned peak load for each specimen. Calculated risks of repair failure during repetitive loading were determined for mean of each statically derived parameter serving as a peak load. Furthermore, we developed a novel objective method to determine the critical load, which is a parameter predicting the survival of the repair in cyclic testing. The mean of statically derived yield load equalled the mean of critical load, justifying its role as a valid surrogate for critical load. However, regarding mean of any determined parameter as a clinically safe threshold is arbitrary due to the natural variation among samples. Until the universal performance of yield load is verified, we recommend employing cyclically derived critical load as primary parameter when comparing different methods of flexor tendon repair. PMID- 27395759 TI - Can finite element models of ballooning procedures yield mechanical response of the cardiovascular site to overexpansion? AB - Patient-specific numerical models could aid the decision-making process for percutaneous valve selection; in order to be fully informative, they should include patient-specific data of both anatomy and mechanics of the implantation site. This information can be derived from routine clinical imaging during the cardiac cycle, but data on the implantation site mechanical response to device expansion are not routinely available. We aim to derive the implantation site response to overexpansion by monitoring pressure/dimensional changes during balloon sizing procedures and by applying a reverse engineering approach using a validated computational balloon model. This study presents the proof of concept for such computational framework tested in-vitro. A finite element (FE) model of a PTS-X405 sizing balloon (NuMed, Inc., USA) was created and validated against bench tests carried out on an ad hoc experimental apparatus: first on the balloon alone to replicate free expansion; second on the inflation of the balloon in a rapid prototyped cylinder with material deemed suitable for replicating pulmonary arteries in order to validate balloon/implantation site interaction algorithm. Finally, the balloon was inflated inside a compliant rapid prototyped patient specific right ventricular outflow tract to test the validity of the approach. The corresponding FE simulation was set up to iteratively infer the mechanical response of the anatomical model. The test in this simplified condition confirmed the feasibility of the proposed approach and the potential for this methodology to provide patient-specific information on mechanical response of the implantation site when overexpanded, ultimately for more realistic computational simulations in patient-specific settings. PMID- 27395760 TI - A validated methodology for patient specific computational modeling of self expandable transcatheter aortic valve implantation. AB - Leakage of blood alongside the implant is a relatively frequent and life-limiting complication after transcatheter aortic valve implantation. The aim of this study is to develop and validate a workflow to simulate the implantation prior to the intervention. Based on the simulation outcome, the amount of leakage is estimated in order to evaluate the risk of a severe complication. A finite element model of the stent implantation in 10 patients was created based on a pre-operative computed tomography scan. All 10 patients also received a follow-up computed tomography scan, after the implantation. This scan was used to extract the deformed geometry of the stent and the position of the calcifications for validation of the simulation results. The maximal average perimeter difference between the simulated stent and the post-operative stent is 2.9+/-2.1mm, and occurs at the bottom of the device. The sensitivity of the simulation to the soft tissue material parameters and aortic root wall thickness was tested. The maximal diameter deviation of 6% occurred when the thickness of the aortic root was doubled. The result of the leakage analysis based on the distance between the simulated stent and the surrounding aortic root corresponded well when no regurgitation was observed. The developed tools have the potential to reduce the occurrence and severity of leakage by providing the clinician with additional information prior to the intervention. The simulated geometry and estimated leakage can help decide on the best implant type, size and position before treatment. PMID- 27395761 TI - Selection criteria for hepatic resection in intermediate-stage (BCLC stage B) multiple hepatocellular carcinoma. AB - BACKGROUND: Several reports have suggested that hepatic resection provides a survival benefit in patients with hepatocellular carcinoma (HCC) at the intermediate stage of the Barcelona Clinic Liver Cancer classification (BCLC-B). The operative indications for multiple BCLC-B have not been established, however. The aim of this study was to clarify the survival benefit of hepatic resection for multinodular BCLC-B HCC. METHODS: We retrospectively analyzed 85 patients with BCLC-B HCC who underwent liver resection. To evaluate clinicopathologic factors and survival, we divided the patients into 3 types based on radiologic findings regarding tumor number and maximum tumor diameter: type 1, up to 3 lesions <5 cm; type 2, up to 3 lesions >=5 cm or 4 nodules of any size; type 3, >4 nodules. RESULTS: Thirty-four patients were classified as type 1, 32 as type 2, and 19 as type 3. The 1-, 3-, and 5-year survival in type 1 were 97.1%, 87.4%, and 75.2%, respectively. Those in type 2 were 84.0%, 74.0%, and 63.0%, and those in type 3 were 64.9%, 55.7%, and 37.1%, respectively. The overall survival of type 1 patients was significantly better than that of type 3 patients. The prognosis of type 2 patients was worse than that of type 1 patients and better than that of type 3. Multivariate analysis identified radiologic tumor size and tumor number as independent prognostic factors. CONCLUSION: Our findings suggest that hepatic resection should be considered a radical treatment for multinodular BCLC-B HCC. Our subclassification can be applied to select the initial treatment and when making decisions regarding hepatic resection of BCLC-B HCC with multiple nodules. PMID- 27395762 TI - The impact of surgeon volume on colostomy reversal outcomes after Hartmann's procedure for diverticulitis. AB - BACKGROUND: Colostomy reversal after Hartmann's procedure for diverticulitis is a morbid procedure, and studies investigating factors associated with outcomes are lacking. This study identifies patient, surgeon, and hospital-level factors associated with perioperative outcomes after stoma reversal. METHODS: The Statewide Planning and Research Cooperative System was queried for urgent/emergency Hartmann's procedures for diverticulitis between 2000-2012 in New York State and subsequent colostomy reversal within 1 year of the procedure. Surgeon and hospital volume were categorized into tertiles based on the annual number of colorectal resections performed each year. Bivariate and mixed-effects analyses were used to assess the association between patient, surgeon, and hospital-level factors and perioperative outcomes after colostomy reversal, including a laparoscopic approach; duration of stay; intensive care unit admission; complications; mortality; and 30-day, unscheduled readmission. RESULTS: Among 10,487 patients who underwent Hartmann's procedure and survived to discharge, 63% had the colostomy reversed within 1 year. After controlling for patient, surgeon, and hospital-level factors, high-volume surgeons (>=40 colorectal resections/yr) were independently associated with higher odds of a laparoscopic approach (unadjusted rates: 14% vs 7.6%; adjusted odds ratio = 1.84, 95% confidence interval = 1.12, 3.00), shorter duration of stay (median: 6 versus 7 days; adjusted incidence rate ratio = 0.87, 95% confidence interval = 0.81, 0.95), and lower odds of 90-day mortality (unadjusted rates: 0.4% vs 1.0%; adjusted odds ratio = 0.30, 95% confidence interval = 0.10, 0.88) compared with low-volume surgeons (1-15 colorectal resections/yr). CONCLUSION: High-volume surgeons are associated with better perioperative outcomes and lower health care utilization after Hartmann's reversal for diverticulitis. These findings support referral to high-volume surgeons for colostomy reversal. PMID- 27395763 TI - British merchant seafarers 1900-2010: A history of extreme risks of mortality from infectious disease. AB - BACKGROUND: This study established trends in major infectious disease mortality in British merchant shipping from 1900 to 2010 as compared with the British male working population and the Royal Navy. METHODS: A population mortality study of six infectious diseases using annual government mortality returns and death inquiry files for British merchant shipping and the Royal Navy, and official mortality data for the general male working aged population. FINDINGS: Relative mortality risks for each disease were increased significantly in British merchant shipping when compared with the general population; malaria by 58.2 fold, yellow fever (6276), typhoid (9.5), cholera (1734), dysentery (20.6) and smallpox (142). For all six diseases combined, relative mortality risks were 21.5 compared with the general population and 3.5 compared with the Royal Navy. Mortality trend patterns varied between diseases, but reductions in mortality in British merchant shipping consistently lagged many years behind those in both the British general population and the Royal Navy. CONCLUSIONS: Merchant seamen were at far higher risk of death than probably any other occupational group of the population. Much of these excess risks came from exposure to infection in unhygienic and tropical ports, although some was a result of neglect of feasible preventative measures. PMID- 27395764 TI - IL-10/microRNA-155/SHIP-1 signaling pathway is crucial for commensal bacteria induced spontaneous colitis. AB - Interleukin 10 (IL-10) microRNA-155 (miR-155)/Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1) signaling pathway plays an important role in maintaining immune homeostasis. We aimed to determine and characterize the changes induced by commensal bacteria on the IL-10/miR-155/SHIP-1 signaling pathway, as well as the potential therapeutic effects of anti-miR-155 on colitis in IL-10 deficient (IL-10(-)/(-)) mice. Age- and sex-matched C57BL/6 IL-10(-)/(-) and wild type mice were transferred from a germ-free environment to a specific pathogen free condition. Part of IL-10(-)/(-) mice were then treated with anti miR-155. IL-10/miR-155/SHIP-1 signaling pathway was evaluated and the therapeutic effects of anti-miR-155 treatment on colitis in IL-10(-)/(-) mice was assessed. The expression and the relationship of IL-10, miR-155, and SHIP-1 were also measured in patients with active Crohn's colitis. IL-10/miR-155/SHIP-1 signaling pathway was activated in IL-10(-)/(-) mice transferring from a germ-free environment to a specific pathogen free condition. Anti-miR-155 treatment significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of anti-miR-155 was associated with a restoration of SHIP-1 signaling pathway. The relationship of IL-10, miR-155, and SHIP-1 was confirmed in human study using samples from patients with active Crohn's colitis. IL-10/miR-155/SHIP-1 pathways play a critical role in commensal bacteria induced colitis and miR-155 may be a potential therapeutic target for human inflammatory bowel disease. PMID- 27395765 TI - WFS1 in Optic Neuropathies: Mutation Findings in Nonsyndromic Optic Atrophy and Assessment of Clinical Severity. AB - PURPOSE: To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment. DESIGN: Retrospective molecular genetic and clinical study. PARTICIPANTS: Patients with OA followed at a national referral center specialized in genetic sensory diseases. METHODS: Mutation screening in WFS1 was performed by Sanger sequencing. WFS1-positive patients were evaluated on visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness using time-domain (TD) or spectral-domain (SD) optical coherence tomography (OCT). Statistical analysis was performed. MAIN OUTCOME MEASURES: Mutation identification, VA values, and RNFL thickness in sectors. RESULTS: Biallelic WFS1 mutations were found in 3 of 24 unrelated patients (15%) with autosomal recessive nonsyndromic optic atrophy (arNSOA) and in 8 patients with autosomal recessive Wolfram syndrome (arWS) associated with diabetes mellitus and OA. Heterozygous mutations were found in 4 of 20 unrelated patients (20%) with autosomal dominant OA. The 4 WFS1-mutated patients of this latter group with hearing loss were diagnosed with autosomal dominant Wolfram-like syndrome (adWLS). Most patients had VA decrease, with logarithm of the minimum angle of resolution (logMAR) values lower in arWS than in arNSOA (1.530 vs. 0.440; P = 0.026) or adWLS (0.240; P = 0.006) but not differing between arNSOA and adWLS (P = 0.879). All patients had decreased RNFL thickness that was worse in arWS than in arNSOA (SD OCT, 35.50 vs. 53.80 MUm; P = 0.018) or adWLS (TD-OCT, 45.84 vs. 59.33 MUm; P = 0.049). The greatest difference was found in the inferior bundle. Visual acuity was negatively correlated with RNFL thickness (r = -0.89; P = 0.003 in SD OCT and r = -0.75; P = 0.01 in TD OCT). CONCLUSIONS: WFS1 is a gene causing arNSOA. Patients with this condition had significantly less visual impairment than those with arWS. Thus systematic screening of WFS1 must be performed in isolated, sporadic, or familial optic atrophies. PMID- 27395766 TI - Detecting Preperimetric Glaucoma with Standard Automated Perimetry Using a Deep Learning Classifier. AB - PURPOSE: To differentiate the visual fields (VFs) of preperimetric open-angle glaucoma (OAG) patients from the VFs of healthy eyes using a deep learning (DL) method. DESIGN: Cohort study. PARTICIPANTS: One hundred seventy-one preperimetric glaucoma VFs (PPGVFs) from 53 eyes in 51 OAG patients and 108 healthy eyes of 87 healthy participants. METHODS: Preperimetric glaucoma VFs were defined as all VFs before a first diagnosis of manifest glaucoma (Anderson-Patella's criteria). In total, 171 PPGVFs from 53 eyes in 51 OAG patients and 108 VFs from 108 healthy eyes in 87 healthy participants were analyzed (all VFs were tested using the Humphrey Field Analyzer 30-2 program; Carl Zeiss Meditec, Dublin, CA). The 52 total deviation, mean deviation, and pattern standard deviation values were used as predictors in the DL classifier: a deep feed-forward neural network (FNN), along with other machine learning (ML) methods, including random forests (RF), gradient boosting, support vector machine, and neural network (NN). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of discrimination for each method. MAIN OUTCOME MEASURES: The AUCs obtained with each classifier method. RESULTS: A significantly larger AUC of 92.6% (95% confidence interval [CI], 89.8%-95.4%) was obtained using the deep FNN classifier compared with all other ML methods: 79.0% (95% CI, 73.5%-84.5%) with RF, 77.6% (95% CI, 71.7%-83.5%) with gradient boosting, 71.2% (95% CI, 65.0% 77.5%), and 66.7% (95% CI, 60.1%-73.3%) with NN. CONCLUSIONS: Preperimetric glaucoma VFs can be distinguished from healthy VFs with very high accuracy using a deep FNN classifier. PMID- 27395767 TI - Oxidative stress and inflammation in schizophrenia. PMID- 27395768 TI - Development and Testing of a 3-Item Screening Tool for Problematic Internet Use. AB - OBJECTIVE: To develop and validate the Problematic and Risky Internet Use Screening Scale (PRIUSS)-3 screening scale, a short scale to screen for Problematic Internet Use. STUDY DESIGN: This scale development study applied standard processes using separate samples for training and testing datasets. We recruited participants from schools and colleges in 6 states and 2 countries. We selected 3 initial versions of a PRIUSS-3 using correlation to the PRIUSS-18 score. We evaluated these 3 potential screening scales for conceptual coherence, factor loading, sensitivity, and specificity. We selected a 3-item screening tool and evaluated it in 2 separate testing sets using receiver operating curves. RESULTS: Our study sample included 1079 adolescents and young adults. The PRIUSS 3 included items addressing anxiety when away from the Internet, loss of motivation when on the Internet, and feelings of withdrawal when away from the Internet. This screening scale had a sensitivity of 100% and specificity of 69%. A score of >=3 on the PRIUSS-3 was the threshold to follow up with the PRIUSS-18. DISCUSSION: Similar to other clinical screening tools, the PRIUSS-3 can be administered quickly in a clinical or research setting. Positive screens should be followed by administering the full PRIUSS-18. Given the pervasive presence of the Internet in youth's lives, screening and counseling for Problematic Internet Use can be facilitated by use of this validated screening tool. PMID- 27395769 TI - Autophagy and Immune Senescence. AB - With extension of the average lifespan, aging has become a heavy burden in society. Immune senescence is a key risk factor for many age-related diseases such as cancer and increased infections in the elderly, and hence has elicited much attention in recent years. As our body's guardian, the immune system maintains systemic health through removal of pathogens and damage. Autophagy is an important cellular 'clearance' process by which a cell internally delivers damaged organelles and macromolecules to lysosomes for degradation. Here, we discuss the most current knowledge of how impaired autophagy can lead to cellular and immune senescence. We also provide an overview, with examples, of the clinical potential of exploiting autophagy to delay immune senescence and/or rejuvenate immunity to treat various age-related diseases. PMID- 27395770 TI - Concepts in diagnosis and therapy for male reproductive impairment. AB - An accurate medical history and directed physical examination are essential in diagnosis of male infertility. We review the hormonal assessments and specific genetic analyses that are useful additional tests, and detail other evidence based examinations that are available to help guide therapeutic strategies. By contrast with female infertility treatments-especially hormonal manipulations to stimulate or enhance oocyte production-spermatogenesis and sperm quality abnormalities are much more difficult to affect positively. In general, a healthy lifestyle can improve sperm quality. A few men have conditions in which evidence based therapies can increase their chances for natural conception. In this second of two papers in The Lancet Diabetes and Endocrinology Series on male reproductive impairment, we examine the agreements and controversies that surround several of these conditions. When we are not able to cure, correct, or mitigate the cause of conditions such as severe oligozoospermia, non-remedial ductal obstruction, and absence of sperm fertilising ability, assisted reproductive technologies, such as in-vitro fertilisation (IVF) with intracytoplasmic sperm injection (ICSI), can be used as an adjunctive measure to allow for biological paternity. Not considered possible just two decades ago, azoospermia due to testicular failure, including 47,XXY (Klinefelter syndrome), is now treatable in approximately 50% of cases when combining surgical harvesting of testicular sperm and ICSI. Although genetic fatherhood is now possible for many men previously considered sterile, it is crucial to discover and abrogate causes as best possible, provide reliable and evidenced-based therapy, consider seriously the health and wellness of any offspring conceived, and always view infertility as a possible symptom of a more general or constitutional disease. PMID- 27395771 TI - Novel concepts in the aetiology of male reproductive impairment. AB - Infertility is a widespread problem and a male contribution is involved in 20-70% of affected couples. As a man's fertility relies on the quantity and quality of his sperm, semen analysis is generally used as the proxy to estimate fertility or gain insight into the underlying reasons for infertility. Male reproductive impairment might result from factors that affect sperm production, quality, function, or transport. Although in most men the origin of infertility remains unexplained, genetic causes are increasingly being discovered. In this first of two papers in The Lancet Diabetes and Endocrinology Series on male reproductive impairment, we propose a novel, clinically based aetiological construct with a genetic focus, and consider how this might serve as a helpful way to conceptualise a diagnostic algorithm. PMID- 27395772 TI - Virocell Metabolism: Metabolic Innovations During Host-Virus Interactions in the Ocean. AB - Marine viruses are considered to be major ecological, evolutionary, and biogeochemical drivers of the marine environment, responsible for nutrient recycling and determining species composition. Viruses can re-shape their host's metabolic network during infection, generating the virocell-a unique metabolic state that supports their specific requirement. Here we discuss the concept of 'virocell metabolism' and its formation by rewiring of host-encoded metabolic networks, or by introducing virus-encoded auxiliary metabolic genes which provide the virocell with novel metabolic capabilities. The ecological role of marine viruses is commonly assessed by their relative abundance and phylogenetic diversity, lacking the ability to assess the dynamics of active viral infection. The new ability to define a unique metabolic state of the virocell will expand the current virion-centric approaches in order to quantify the impact of marine viruses on microbial food webs. PMID- 27395773 TI - Wnt/beta-catenin signaling in melanoma: Preclinical rationale and novel therapeutic insights. AB - WNT signaling regulates embryonic development and tissue homeostasis in the adult stage. Evolutionarily, activation of the WNT pathway is triggered by a large family of cytokines and activates a broad spectrum of downstream targets through two independent branches mediated by beta-catenin (defined as canonical pathway) or PLC and small GTPase (defined as non-canonical pathway), respectively. Recent studies revealed the crucial role of WNT in the maintenance of cell metabolism and stemness as well as its deregulation in tumourigenesis and malignant transformation through oncogenic reprogramming, which contributes to cancer cell proliferation and differentiation, survival, stress response and resistance. In addition, multiple functional mutations discovered in human tumours have been reported to cause malignancy, indicating this pathway as a novel therapeutic target in oncology. Notably, emerging data highlights its involvement in the crosstalk between immune and cancer cells. However, contradictory effects have been also observed in different pre-clinical models when strategic(???) inhibitors are tested. In this review, we address the multifaceted regulatory mechanisms of WNT signaling in cancer, with a particular focus on current melanoma therapy, which has witnessed dramatic improvement in the last five years. PMID- 27395774 TI - The utility of ultrasonography to confirm proper endotracheal tube placement in neonates. PMID- 27395775 TI - Patients' Perspectives on Their Dry Eye Disease. AB - PURPOSE: Although it has been known that patients' perspectives on their disease can significantly affect their level of functional disability as well as disease outcome, limited data are available on patients' perceptions of their dry eye disease (DED). The aim of this questionnaire-based study was to evaluate patients' perspectives on their DED. METHODS: This cross-sectional study included 91 patients with DED. In addition to clinical evaluation, all patients completed a questionnaire to evaluate their perspectives on their DED. This included their satisfaction with understanding DED, their opinion on the easiness of following doctors' advice, their opinion on the effectiveness of the treatment, their satisfaction with the eye care, and their general outlook on DED. RESULTS: This study included 75 (82%) women and 16 men (18%) with a mean age of 57 +/- 14 years who had been treated for DED for 5.2 +/- 5.4 years. 93% of the patients were satisfied with their understanding of DED, and 76% found it easy to follow their doctors' advice for DED management. Furthermore, 95% thought that the DED treatment had been helpful and 95% were satisfied with their eye care for DED. Forty-eight percent expressed optimism regarding the long-term prospects of their DED. CONCLUSIONS: Although the majority of DED patients have positive perspectives on their disease, close to half report a lack of optimism regarding the long-term outlook for their condition. PMID- 27395777 TI - Transcription of Inflammatory Cytokine TNFalpha is Upregulated in Retinal Angiogenesis under Hyperoxia. AB - BACKGROUND/AIMS: Hypoxia induces angiogenesis while hyperoxia promotes vasoregression in the retina. We investigated herein the effect of prolonged hyperoxia on retinal angiogenesis and the underlying mechanism in an oxygen induced retinopathy (OIR) model. METHODS: Vascular morphology was quantified in whole-mount retina from the mice subjected to the conventional OIR model (c-OIR) or the OIR model with prolonged hyperoxia (p-OIR). Expressions of genes related to angiogenesis were determined by real-time PCR. RESULTS: p-OIR retinas showed few intraretinal neovascular tufts at the border of avascular zones, lacking preretinal neovascularization, whereas c-OIR retinas had numerous preretinal neovascularizations. p-OIR retinas demonstrated outgrowth of capillaries in the deep layers despite persistent hyperoxia and possess a larger avascular zone compared with the c-OIR retinas. The capillaries in the p-OIR retinas were well formed in contrast to those in the c-OIR retinas. p-OIR retinas expressed significantly higher TNFalpha (~4 fold) than c-OIR retinas. The expression of vascular endothelial growth factor, Erythropoietin, Angiopoietin 1 and 2 remained unchanged. CONCLUSION: Our data demonstrate that TNFalpha transcription is increased in hyperoxia-promoted retinal angiogenesis, implicating it, in association with low VEGF levels, as a possible proponent in retinal angiogenesis under hyperoxia. PMID- 27395776 TI - Evaporation and Hydrocarbon Chain Conformation of Surface Lipid Films. AB - PURPOSE: The inhibition of the rate of evaporation (Revap) by surface lipids is relevant to reservoirs and dry eye. Our aim was to test the idea that lipid surface films inhibit Revap. METHODS: Revap were determined gravimetrically. Hydrocarbon chain conformation and structure were measured using a Raman microscope. Six 1-hydroxyl hydrocarbons (11-24 carbons in length) and human meibum were studied. Reflex tears were obtained from a 62-year-old male. RESULTS: The Raman scattering intensity of the lipid film deviated by about 7 % for hydroxyl lipids and varied by 21 % for meibum films across the entire film at a resolution of 5 MUm2. All of the surface lipids were ordered. Revap of the shorter chain hydroxyl lipids were slightly (7%) but significantly lower compared with the longer chain hydroxyl lipids. Revap of both groups was essentially similar to that of buffer. A hydroxyl lipid film did not influence Revap over an estimated average thickness range of 0.69 to >6.9 MUm. Revap of human tears and buffer with and without human meibum (34.4 MUm thick) was not significantly different. Revap of human tears was not significantly different from buffer. CONCLUSIONS: Human meibum and hydroxyl lipids, regardless of their fluidity, chain length, or thickness did not inhibit Revap of buffer or tears even though they completely covered the surface. It is unlikely that hydroxyl lipids can be used to inhibit Revap of reservoirs. Our data do not support the widely accepted (yet unconfirmed) idea that the tear film lipid layer inhibits Revap of tears. PMID- 27395778 TI - Out of Africa: Phylogeny and biogeography of the widespread genus Acanthodactylus (Reptilia: Lacertidae). AB - Acanthodactylus lizards are among the most diverse and widespread diurnal reptiles in the arid regions spanning from North Africa across to western India. Acanthodactylus constitutes the most species-rich genus in the family Lacertidae, with over 40 recognized species inhabiting a wide variety of dry habitats. The genus has seldom undergone taxonomic revisions, and although there are a number of described species and species-groups, their boundaries, as well as their interspecific relationships, remain largely unresolved. We constructed a multilocus phylogeny, combining data from two mitochondrial (12S, cytb) and three nuclear (MC1R, ACM4, c-mos) markers for 302 individuals belonging to 36 known species, providing the first large-scale time-calibrated molecular phylogeny of the genus. We evaluated phylogenetic relationships between and within species groups, and assessed Acanthodactylus biogeography across its known range. Acanthodactylus cladogenesis is estimated to have originated in Africa due to vicariance and dispersal events from the Oligocene onwards. Radiation started with the separation into three clades: the Western and scutellatus clades largely distributed in North Africa, and the Eastern clade occurring mostly in south-west Asia. Most Acanthodactylus species diverged during the Miocene, possibly as a result of regional geological instability and climatic changes. We support most of the current taxonomic classifications and phylogenetic relationships, and provide genetic validity for most species. We reveal a new distinct blanfordii species-group, suggest new phylogenetic positions (A. hardyi, A. masirae), and synonymize several species and subspecies (A. lineomaculatus, A. boskianus khattensis and A. b. nigeriensis) with their phylogenetically closely-related species. We recommend a thorough systematic revision of taxa, such as A. guineensis, A. grandis, A. dumerilii, A. senegalensis and the pardalis and erythrurus species-groups, which exhibit high levels of intraspecific variability, and clear evidence of phylogenetic complexity. PMID- 27395779 TI - Methodological congruence in phylogenomic analyses with morphological support for teiid lizards (Sauria: Teiidae). AB - A well-known issue in phylogenetics is discordance among gene trees, species trees, morphology, and other data types. Gene-tree discordance is often caused by incomplete lineage sorting, lateral gene transfer, and gene duplication. Multispecies-coalescent methods can account for incomplete lineage sorting and are believed by many to be more accurate than concatenation. However, simulation studies and empirical data have demonstrated that concatenation and species tree methods often recover similar topologies. We use three popular methods of phylogenetic reconstruction (one concatenation, two species tree) to evaluate relationships within Teiidae. These lizards are distributed across the United States to Argentina and the West Indies, and their classification has been controversial due to incomplete sampling and the discordance among various character types (chromosomes, DNA, musculature, osteology, etc.) used to reconstruct phylogenetic relationships. Recent morphological and molecular analyses of the group resurrected three genera and created five new genera to resolve non-monophyly in three historically ill-defined genera: Ameiva, Cnemidophorus, and Tupinambis. Here, we assess the phylogenetic relationships of the Teiidae using "next-generation" anchored-phylogenomics sequencing. Our final alignment includes 316 loci (488,656bp DNA) for 244 individuals (56 species of teiids, representing all currently recognized genera) and all three methods (ExaML, MP-EST, and ASTRAL-II) recovered essentially identical topologies. Our results are basically in agreement with recent results from morphology and smaller molecular datasets, showing support for monophyly of the eight new genera. Interestingly, even with hundreds of loci, the relationships among some genera in Tupinambinae remain ambiguous (i.e. low nodal support for the position of Salvator and Dracaena). PMID- 27395780 TI - Histomorphometric and transcriptomic features characterize silk glands' development during the molt to intermolt transition process in silkworm. AB - The molt-intermolt cycle is an essential feature in holometabolous and hemimetabolous insects' development. In the silkworm, silk glands are under dramatic morphological and functional changes with fibroin genes' transcription being repeatedly turned off and on during the molt-intermolt cycles. However, the molecular mechanisms controlling it are still unknown. Here, silk gland's histomorphology and transcriptome analysis were used to characterize changes in its structure and gene expression patterns from molt to intermolt stages. By using section staining and transmission electron microscope, a renewable cell damage was detected in the silk gland at the molt stage, and an increased number of autophagosomes and lysosomes were found in silk gland cells' cytoplasm. Next, by using RNA sequencing, 54,578,413 reads were obtained, of which 85% were mapped to the silkworm reference genome. The expression level analysis of silk protein genes and silk gland transcription factors revealed that fibroin heavy chain, fibroin light chain, P25/fhx, sericin1, sericin3 and Dimm had consistent alteration trends in temporal expression. In addition, differentially expressed genes (DEGs) were identified, and most of the DEGs associated with ecdysone signal transduction, mRNA degradation, protein proteolysis, and autophagy were significantly down-regulated in the transition from molt to intermolt, suggesting that these pathways were activated for the silk gland renewal. These findings provide insights into the molecular mechanisms of silk gland development and silk protein genes transcriptional regulation during the molt to intermolt transition process. PMID- 27395781 TI - Dipeptidyl peptidase 4 - An important digestive peptidase in Tenebrio molitor larvae. AB - Dipeptidyl peptidase 4 (DPP 4) is a proline specific serine peptidase that plays an important role in different regulatory processes in mammals. In this report, we isolated and characterized a unique secreted digestive DPP 4 from the anterior midgut of a stored product pest, Tenebrio molitor larvae (TmDPP 4), with a biological function different than that of the well-studied mammalian DPP 4. The sequence of the purified enzyme was confirmed by mass-spectrometry, and was identical to the translated RNA sequence found in a gut EST database. The purified peptidase was characterized according to its localization in the midgut, and substrate specificity and inhibitor sensitivity were compared with those of human recombinant DPP 4 (rhDPP 4). The T. molitor enzyme was localized mainly in the anterior midgut of the larvae, and 81% of the activity was found in the fraction of soluble gut contents, while human DPP 4 is a membrane enzyme. TmDPP 4 was stable in the pH range 5.0-9.0, with an optimum activity at pH 7.9, similar to human DPP 4. Only specific inhibitors of serine peptidases, diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride, suppressed TmDPP 4 activity, and the specific dipeptidyl peptidase inhibitor vildagliptin was most potent. The highest rate of TmDPP 4 hydrolysis was found for the synthetic substrate Arg-Pro pNA, while Ala-Pro-pNA was a better substrate for rhDPP 4. Related to its function in the insect midgut, TmDPP 4 efficiently hydrolyzed the wheat storage proteins gliadins, which are major dietary proteins of T. molitor. PMID- 27395782 TI - Important practice lessons from the SPRINT study beyond the blood pressure goal: all well known and now confirmed. PMID- 27395783 TI - Significance of adjusting salt intake by body weight in the evaluation of dietary salt and blood pressure. AB - The close association between dietary salt and hypertension is well established. However, previous studies generally assessed salt intake without adjustment for body weight. Herein, we investigated the significance of body weight-adjusted salt intake in the general population. The present cross-sectional study included 7629 participants from our yearly physical checkup program, and their salt intake was assessed using a spot urine test to estimate 24-hour urinary salt excretion. Total salt intake increased with increasing body weight. Body weight-adjusted salt intake was greater in participants with hypertension than in those without hypertension. Systolic blood pressure, estimated glomerular filtration rate, and urinary albumin were independently correlated with body weight-adjusted salt intake after adjustment for possible cardiovascular risk factors. Excessive body weight-adjusted salt intake could be related to an increase in blood pressure and hypertensive organ damage. Adjustment for body weight might therefore provide clinically important information when assessing individual salt intake. PMID- 27395784 TI - Lateral hypothalamus orexinergic system modulates the stress effect on pentylenetetrazol induced seizures through corticotropin releasing hormone receptor type 1. AB - Stress is a trigger factor for seizure initiation which activates hypothalamic pituitary adrenal (HPA) axis as well other brain areas. In this respect, corticotropin releasing hormone (CRH) and lateral hypothalamus (LH) orexinergic system are involved in seizure occurrence. In this study, we investigated the role of LH area and orexin expression in (mediation of) stress effect on pentylenetetrazol (PTZ) -induced seizures with hippocampal involvement. Two mild foot shock stresses were applied to intact and adrenalectomized animals; with or without CRHr1 blocking (NBI 27914) in the LH area. Then, changes in orexin production were evaluated by RT-PCR. Intravenous PTZ infusion (25 mg/ml) -induced convulsions were scored upon modified Racine scale. Finally, hippocampal glutamate and GABA were evaluated to study excitability changes. We demonstrated that the duration and severity of convulsions in stress-induced as well as adrenalectomized group were increased. Plasma corticosterone (CRT) level and orexin mRNA expression were built up in the stress and/or seizure groups. Furthermore, glutamate and GABA content was increased and decreased respectively due to stress and seizures. In contrast, rats receiving CRHr1 inhibitor showed reduced severity and duration of seizures, increased GABA, decreased glutamate and corticosterone and also orexin mRNA compared to the inhibitor free rats. Stress and adrenalectomy induced augmenting effect on seizure severity and duration and the subsequent reduction due to CRHr1 blocking with parallel orexin mRNA changes, indicated the likely involvement of CRH1r induced orexin expression of the LH in gating stress effect on convulsions. PMID- 27395786 TI - Metabotropic glutamate receptor, mGlu5, regulates hippocampal synaptic plasticity and is required for tetanisation-triggered changes in theta and gamma oscillations. AB - Hippocampal synaptic plasticity and learning are regulated by metabotropic glutamate receptors (mGlu) and particularly by mGlu5. In the hippocampus, synaptic plasticity is tightly linked to neuronal network oscillations in theta (5-10 Hz) and gamma (~30-100 Hz) frequency ranges, and specific changes in theta and gamma spectral power can predict for the success of patterned afferent stimulation in inducing robust long-term potentiation (LTP). In this study, we hypothesized that activation of mGlu5 mediates tetanisation-driven changes in network oscillations and thereby determines the longevity of LTP. To explore this, we applied high-frequency stimulation (HFS) to the perforant path input to the dentate gyrus (DG), in the presence of the negative allosteric modulator, 2 methyl-6-(phenylethynyl)pyridine (MPEP), or the positive allosteric modulator (S) (4-fluorophenyl)-[3-(3-(3-(4-fluorophenyl)-[1,2,4]oxadiazol-5-yl)-piperidin-1 yl)]methanone (ADX47273). In freely behaving rats, administration of MPEP resulted in a significant impairment, whereas treatment with ADX47273 led to a significant enhancement, of LTP (>24 h) compared to vehicle-treated controls. Allosteric potentiation of mGlu5 also resulted in a significantly greater increase of the spectral power of theta and gamma oscillations within the period of 300 s after HFS, as compared to MPEP-treated animals or controls. Our findings show that the regulation of hippocampal LTP by mGlu5 is associated with modulation of network oscillatory activity in the period shortly after LTP induction. Taken together, these data demonstrate that changes in the spectral contents of local field activity that occur in response to patterned afferent stimulation require activation of mGlu5 and may be instrumental for the successful expression of persistent LTP. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. PMID- 27395785 TI - Antidepressant treatment differentially affects the phenotype of high and low stress reactive mice. AB - Modelling key endophenotypes can be a powerful approach to gain insight into mechanisms underlying the aetiology and pathophysiology of neuropsychiatric disorders. Based on evidence of stress hormone system dysregulations in depression, the Stress Reactivity (SR) mouse model has been generated by a selective breeding approach for extremes in HPA axis reactivity, resulting in high (HR), intermediate (IR) and low (LR) reactive mice. The characterisation of their phenotypic alterations has highlighted many similarities of HR and LR mice with the melancholic and atypical depression, respectively. We therefore aimed to examine whether the antidepressant fluoxetine (10 mg/kg/day i.p., 4-5 weeks) can ameliorate the phenotypic characteristics of HR and LR mice in neuroendocrine functions (HPA axis basal activity, stress reactivity, negative feedback), emotional reactivity/coping-strategy (open field, forced swim tests), spatial learning/memory (Morris water-maze) and hippocampal neurogenesis. Line differences in HPA axis reactivity were maintained under fluoxetine treatment. However, we observed fluoxetine effects on glucocorticoid-induced negative feedback, stress-coping behaviours, cognitive functions and neurogenesis. Specifically, our results revealed line-dependent consequences of fluoxetine treatment: (1) an amelioration of the 'melancholic-like' features of HR mice (reversing the negative feedback resistance, the hyperactive coping style and the memory deficits; increasing hippocampal neurogenesis); (2) an exacerbation of the phenotypic deviations of LR mice (increasing their pronounced negative feedback and passive coping style). Thus, these findings support the predictive validity of antidepressant treatment in the HR mouse line and emphasize the translational value of the SR mouse model for the development of therapeutic strategies based on endophenotype-driven classifications. PMID- 27395787 TI - Nucleus incertus Orexin2 receptors mediate alcohol seeking in rats. AB - Alcoholism is a chronic relapsing disorder and a major global health problem. Stress is a key precipitant of relapse in human alcoholics and in animal models of alcohol seeking. The brainstem nucleus incertus (NI) contains a population of relaxin-3 neurons that are highly responsive to psychological stressors; and the ascending NI relaxin-3/RXFP3 signalling system is implicated in stress-induced reinstatement of alcohol seeking. The NI receives orexinergic innervation and expresses orexin1 (OX1) and orexin2 (OX2) receptor mRNA. In alcohol-preferring (iP) rats, we examined the impact of yohimbine-induced reinstatement of alcohol seeking on orexin neuronal activation, and the effect of bilateral injections into NI of the OX1 receptor antagonist, SB-334867 (n = 16) or the OX2 receptor antagonist, TCS-OX2-29 (n = 8) on stress-induced reinstatement of alcohol seeking. We also assessed the effects of orexin-A on NI neuronal activity and the involvement of OX1 and OX2 receptors using whole cell patch-clamp recordings in rat brain slices. Yohimbine-induced reinstatement of alcohol seeking activated orexin neurons. Bilateral NI injections of TCS-OX2-29 attenuated yohimbine induced reinstatement of alcohol seeking. In contrast, intra-NI injection of SB 334867 had no significant effect. In line with these data, orexin-A (600 nM) depolarized a majority of NI neurons recorded in coronal brain slices (18/28 cells), effects prevented by bath application of TCS-OX2-29 (10 MUM), but not SB 334867 (10 MUM). These data suggest an excitatory orexinergic input to NI contributes to yohimbine-induced reinstatement of alcohol seeking, predominantly via OX2 receptor signalling. PMID- 27395788 TI - Mitochondria from a mouse model of the human infantile neuroaxonal dystrophy (INAD) with genetic defects in VIA iPLA2 have disturbed Ca(2+) regulation with reduction in Ca(2+) capacity. AB - Mutations in the PLA2G6 gene which encodes Ca(2+)-independent phospholipase A2 (VIA iPLA2) were detected in 85% of cases of the inherited degenerative nervous system disorder INAD (infantile neuroaxonal dystrophy, OMIM #256600). However, molecular mechanisms linking these mutations to the disease progression are unclear. VIA iPLA2 is expressed also in mitochondria. Here, we investigate Ca(2+) handling by brain mitochondria derived from mice with hypomorph Pla2g6 allele. These animals with reduced transcript levels (5% of wild type) represent a suitable model for INAD. We demonstrated significant reduction of Ca(2+) uptake rate and Ca(2+) retention capacity in brain mitochondria isolated from this mutant. This phenotype could be mimicked when in wild-type controls VIA iPLA2 was inhibited by S-BEL. Importantly, the reduction could be ameliorated partly by addition of the VIA iPLA2 product, sn-2 lysophosphatidyl-choline. Furthermore, we demonstrated in situ a reduced mitochondrial potential in neurons from mice deficient in VIA iPLA2, which could cause the reduced Ca(2+) uptake rate via the potential-dependent mitochondrial Ca(2+) uniporter. Thus, the disturbances in mitochondrial potential and the changes in Ca(2+) handling were dependent on VIA iPLA2 activity. Reduced mitochondrial Ca(2+) uptake rate and Ca(2+) retention capacity might result in increased vulnerability of mitochondria to the Ca(2+) overload and in disturbed cellular Ca(2+) signaling during INAD. For VIA iPLA2, non-canonical functions beyond sole phospholipid turnover seem to be important, such as regulation of store-operated Ca(2+) entry in cells. Thus, our findings bring new insight into molecular mechanism affected in INAD and highlight the non canonical function of VIA iPLA2 in regulation of mitochondrial Ca(2+) handling. PMID- 27395789 TI - Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinsonism in mice. AB - Parkinson's disease (PD), the most common progressive neurodegenerative movement disorder, results from loss of dopaminergic neurons of substantia nigra pars compacta. These neurons exhibit Cav1.3 channel-dependent pacemaking activity. Epidemiological studies suggest reduced risk for PD in population under long-term antihypertensive therapy with L-type calcium channel antagonists. These prompted us to investigate nimodipine, an L-type calcium channel blocker for neuroprotective effect in cellular and animal models of PD. Nimodipine (0.1-10 MUM) significantly attenuated 1-methyl-4-phenyl pyridinium ion-induced loss in mitochondrial morphology, mitochondrial membrane potential and increases in intracellular calcium levels in SH-SY5Y neuroblastoma cell line as measured respectively employing Mitotracker green staining, TMRM, and Fura-2 fluorescence, but only a feeble neuroprotective effect was observed in MTT assay. Nimodipine dose-dependently reduced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced parkinsonian syndromes (akinesia and catalepsy) and loss in swimming ability in Balb/c mice. It attenuated MPTP-induced loss of dopaminergic tyrosine hydroxylase positive neurons in substantia nigra, improved mitochondrial oxygen consumption and inhibited reactive oxygen species production in the striatal mitochondria measured using dichlorodihydrofluorescein fluorescence, but failed to block striatal dopamine depletion. These results point to an involvement of L type calcium channels in MPTP-induced dopaminergic neuronal death in experimental parkinsonism and more importantly provide evidences for nimodipine to improve mitochondrial integrity and function. PMID- 27395790 TI - Advances in understanding the functions of native GlyT1 and GlyT2 neuronal glycine transporters. AB - Glycine can be substrate for two transporters: GlyT1, largely expressed by astrocytes but also by some non-glycinergic neurons, and GlyT2, most frequently present in glycine-storing nerve endings. In morphological studies, GlyT2 expression had been found to be restricted to caudal regions, being almost undetectable in neocortex and hippocampus. Here, we compared the uptake activities of GlyT1 and GlyT2 in synaptosomes purified from mouse spinal cord, cerebellum, neocortex and hippocampus. Although, as expected, [(3)H]glycine uptake was significantly lower in telencephalic than in caudal regions, selective GlyT2-mediated uptake could be evaluated in all areas. Appropriately, [(3)H]glycine selectively taken up into hippocampal synaptosomes through GlyT2 could be subsequently released by exocytosis. Native GlyT2, which did not contribute to basal release from cerebellum or spinal cord nerve terminals, could mediate release of [(3)H]glycine by transporter reversal in synaptosomes exposed to veratridine. Moreover, GlyT2 transporters could perform Na(+)-dependent homoexchange in response to externally added glycine. In conclusion, transporters of the GlyT2 type exhibited significant uptake also in telencephalic regions, probably because of the elevated driving force related to their stoichiometry. Although glycine release through GlyT2 had been predicted to be a very difficult process, GlyT2 expressed on isolated glycinergic nerve terminals can perform both release by transporter reversal and homoexchange. PMID- 27395791 TI - Sacrificing power for more cost-effective treatment: A techno-economic approach for engineering microbial fuel cells. AB - Microbial fuel cells (MFCs) are a promising energy-positive wastewater treatment technology, however, the system's cost-effectiveness has been overlooked. In this study, two new anode materials - hard felt (HF) and carbon foam (CF) - were evaluated against the standard graphite brush (GB) to determine if using inexpensive materials with less than ideal properties can achieve more cost effective treatment than high-cost, high-performing materials. Using domestic wastewater as the substrate, power densities for the GB, HF and CF-MFCs were 393, 339 and 291 mW m(-2) normalized by cathodic surface area, respectively. Higher power densities correlated with larger anodic surface areas and anodic current densities but not with electrical conductivity. Cyclic voltammetry revealed that redox systems used for extracellular electron transport in the GB, HF and CF-MFCs were similar (-0.143 +/- 0.046, -0.158 +/- 0.004 and -0.100 +/- 0.014 V vs. Ag/AgCl) and that the electrochemical kinetics of the MFCs showed no correlation with their respective electrical conductivity. 16S rRNA sequencing showed the GB, HF and CF microbial community compositions were not statistically different while organic removal rates were nearly identical for all MFCs. The HF-MFC generated a power output to electrode cost (W $(-1)) 1.9 times greater than the GB-MFC, despite producing 14% less power and 15% less anodic current, while having 2.6 times less anodic surface area, 2.1 times larger charge transfer resistance and an electrical conductivity three orders of magnitude lower. The results demonstrate that inexpensive materials are capable of achieving more cost effective treatment than high-performing materials despite generating lower power when treating real wastewater. PMID- 27395792 TI - Mitrocomin from the jellyfish Mitrocoma cellularia with deleted C-terminal tyrosine reveals a higher bioluminescence activity compared to wild type photoprotein. AB - The full-length cDNA genes encoding five new isoforms of Ca(2+)-regulated photoprotein mitrocomin from a small tissue sample of the outer bell margin containing photocytes of only one specimen of the luminous jellyfish Mitrocoma cellularia were cloned, sequenced, and characterized after their expression in Escherichia coli and subsequent purification. The analysis of cDNA nucleotide sequences encoding mitrocomin isoforms allowed suggestion that two isoforms might be the products of two allelic genes differing in one amino acid residue (64R/Q) whereas other isotypes appear as a result of transcriptional mutations. In addition, the crystal structure of mitrocomin was determined at 1.30A resolution which expectedly revealed a high similarity with the structures of other hydromedusan photoproteins. Although mitrocomin isoforms reveal a high degree of identity of amino acid sequences, they vary in specific bioluminescence activities. At that, all isotypes displayed the identical bioluminescence spectra (473-474nm with no shoulder at 400nm). Fluorescence spectra of Ca(2+)-discharged mitrocomins were almost identical to their light emission spectra similar to the case of Ca(2+)-discharged aequorin, but different from Ca(2+)-discharged obelins and clytin which fluorescence is red-shifted by 25-30nm from bioluminescence spectra. The main distinction of mitrocomin from other hydromedusan photoproteins is an additional Tyr at the C-terminus. Using site-directed mutagenesis, we showed that this Tyr is not important for bioluminescence because its deletion even increases specific activity and efficiency of apo-mitrocomin conversion into active photoprotein, in contrast to C-terminal Pro of other photoproteins. Since genes in a population generally exist as different isoforms, it makes us anticipate the cloning of even more isoforms of mitrocomin and other hydromedusan photoproteins with different bioluminescence properties. PMID- 27395793 TI - Sonochemical synthesis, DNA binding, antimicrobial evaluation and in vitro anticancer activity of three new nano-sized Cu(II), Co(II) and Ni(II) chelates based on tri-dentate NOO imine ligands as precursors for metal oxides. AB - Three new nano sized Cu(II), Co(II) and Ni(II) complexes of imine ligand derived from the condensation of 2-amino-3-hydroxypyridine and 3-methoxysalicylaldehyde have been prepared and investigated using various chemical techniques such as NMR, elemental analysis, molar conductance, IR, electronic spectra, TGA and magnetic moment measurements. The obtained chemical analysis data showed that the synthesis of 1:1 (metal:ligand) ratio and octahedral geometry was proposed on the basis of magnetic moment and spectral data studies except the Cu(II) complex which is tetrahedral geometry. Nano-sized particles of the investigated complexes were prepared by sonochemistry method. Furthermore, metal oxides nanoparticles were gained by calcination of the prepared corresponding complexes at 500 degrees C and their structures were characterized by powder x-ray and transmittance electron microscopy. Moreover, the free ligand, its complexes and their metal oxides have been checked in vitro against a number of bacteria and fungi in order to assess their antimicrobial activities. In addition to that, DNA binding of the prepared complexes was tested by many routes such as electronic spectra, viscosity and gel electrophoresis. The results showed that the investigated complexes could bind to DNA via an intercalative mode. The cytotoxicity of the Schiff base complexes on human colon carcinoma cells, (HCT-116 cell line) and Breast carcinoma cells, (MCF-7 cell line) showed potent cytotoxicity effect against growth of carcinoma cells compared to the clinically used Vinblastine standard. PMID- 27395794 TI - Preparation and characterization of a green nano-support for the covalent immobilization of glucoamylase from Neurospora sitophila. AB - The preparation of green nano supports for the covalent immobilization of enzymes is of special interest both from the economic and environmental point of view. In this contribution, we report on the synthesis of phytochemicals coated silver nanoparticles, which were used as a novel green support for the covalent immobilization of glucoamylase isolated from Neurospora sitophila. The aqueous extract of Fagonia indica was used as a source of reducing and capping agents for the reduction of silver ions into silver nanoparticles. The prepared nanoparticles were characterized by various analytical techniques. UV-visible spectroscopy was used to detect the characteristic surface plasmon resonance bands (426, 438nm) of the silver nanoparticles. The biosynthesized silver nanoparticles were mostly spherical in shapes with an average particle size of 30 40nm (TEM and DLS measurements). X-ray diffraction and energy dispersive X-ray studies confirmed the face centered cubic crystalline form and elemental composition of the biogenic silver nanoparticles respectively. FTIR study revealed that plant polyphenolics and protein were mainly involved in the reduction and capping of silver ions. Glucoamylase from Neurospora sitophila was covalently immobilized to these nanoparticles via EDC (1-(3-(dimethylamino) propyl) 3-ethylcarbodiimidehydrochloride) coupling reaction. The immobilized enzyme exhibited higher pH and thermal stabilities as compared to the free enzyme. The kinetic constant (KM) value for the immobilized glucoamylase was higher (0.73mg/mL) than its free counterpart (0.44mg/mL), whereas the Vmax value was slightly higher for the immobilized glucoamylase. The findings of this study conclude that the newly developed green method for the synthesis of green nano support is simple, cost effective and could be successfully used for the immobilization of various enzymes and other macromolecules. PMID- 27395795 TI - Curating a Digital Identity: What Urologists Need to Know About Social Media. PMID- 27395797 TI - In vitro systems to study nephropharmacology: 2D versus 3D models. AB - The conventional 2-dimensional (2D) cell culture is an invaluable tool in, amongst others, cell biology and experimental pharmacology. However, cells cultured in 2D, on the top of stiff plastic plates lose their phenotypical characteristics and fail in recreating the physiological environment found in vivo. This is a fundamental requirement when the goal of the study is to get a rigorous predictive response of human drug action and safety. Recent approaches in the field of renal cell biology are focused on the generation of 3D cell culture models due to the more bona fide features that they exhibit and the fact that they are more closely related to the observed physiological conditions, and better predict in vivo drug handling. In this review, we describe the currently available 3D in vitro models of the kidney, and some future directions for studying renal drug handling, disease modeling and kidney regeneration. PMID- 27395796 TI - Comparative proteomic analysis in Aphis glycines Mutsumura under lambda cyhalothrin insecticide stress. AB - Lambda-cyhalothrin is now widely used in China to control the soybean aphid Aphis glycines. To dissect the resistance mechanism, a laboratory-selected resistant soybean aphid strain (CRR) was established with a 43.42-fold resistance ratio to lambda-cyhalothrin than the susceptible strain (CSS) in adult aphids. In this study, a comparative proteomic analysis between the CRR and CSS strains revealed important differences between the susceptible and resistant strains of soybean aphids for lambda-cyhalothrin. Approximately 493 protein spots were detected in two-dimensional polyacrylamide gel electrophoresis (2-DE). Thirty-six protein spots displayed differential expression of >2-fold in the CRR strain compared to the CSS strain. Out of these 36 protein spots, 21 had elevated and 15 had decreased expression. Twenty-four differentially expressed proteins were identified by MALDI TOF MS/MS and categorized into the functional groups cytoskeleton-related protein, carbohydrate and energy metabolism, protein folding, antioxidant system, and nucleotide and amino acid metabolism. Function analysis showed that cytoskeleton-related proteins and energy metabolism proteins have been associated with the lambda-cyhalothrin resistance of A. glycines. The differential expression of lambda-cyhalothrin responsive proteins reflected the overall change in cellular structure and metabolism after insecticide treatment in aphids. In summary, our studies improve understanding of the molecular mechanism resistance of soybean aphid to lambda-cyhalothrin, which will facilitate the development of rational approaches to improve the management of this pest and to improve the yield of soybean. PMID- 27395798 TI - Nephrogenesis in organoids to develop novel drugs and progenitor cell based therapies. AB - New therapies that are derived from small molecules and stem/progenitor cells should be developed to face the increasing occurrence of end stage renal disease where treatments are currently limited. Over the last decade a significant progress in the knowledge of how the organs are assembled have been made and led to development of novel three-dimensional organoid assays, also for the kidney. Indeed, such organoids provide novel tool to study aspects of drugs nephrotoxicity, openings for renal disease modeling and cell therapy development and may offer solutions for end stage renal disease. PMID- 27395799 TI - A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats. AB - We compared the model performance of two semi-mechanistic pharmacokinetic pharmacodynamic models, the precursor pool model and the agonist-antagonist interaction model, to describe prolactin response following the administration of the dopamine D2 receptor antagonists risperidone, paliperidone or remoxipride in rats. The time course of pituitary dopamine D2 receptor occupancy was also predicted. Male Wistar rats received a single dose (risperidone, paliperidone, remoxipride) or two consecutive doses (remoxipride). Population modeling was applied to fit the pool and interaction models to the prolactin data. The pool model was modified to predict the time course of pituitary D2 receptor occupancy. Unbound plasma concentrations of the D2 receptor antagonists were considered the drivers of the prolactin response. Both models were used to predict prolactin release following multiple doses of paliperidone. Both models described the data well and model performance was comparable. Estimated unbound EC50 for risperidone and paliperidone was 35.1nM (relative standard error 51%) and for remoxipride it was 94.8nM (31%). KI values for these compounds were 11.1nM (21%) and 113nM (27%), respectively. Estimated pituitary D2 receptor occupancies for risperidone and remoxipride were comparable to literature findings. The interaction model better predicted prolactin profiles following multiple paliperidone doses, while the pool model predicted tolerance better. The performance of both models in describing the prolactin profiles was comparable. The pool model could additionally describe the time course of pituitary D2 receptor occupancy. Prolactin response following multiple paliperidone doses was better predicted by the interaction model. PMID- 27395800 TI - Upscaling of a living membrane for bioartificial kidney device. AB - The limited removal of metabolic waste products in dialyzed kidney patients leads to high morbidity and mortality. One powerful solution for a more complete removal of those metabolites might be offered by a bioartificial kidney device (BAK), which contains a hybrid "living membrane" with functional proximal tubule epithelial cells (PTEC). These cells are supported by an artificial functionalized hollow fiber membrane (HFM) and are able to actively remove the waste products. In our earlier studies, conditionally immortalized human PTEC (ciPTEC) showed to express functional organic cationic transporter 2 (OCT2) when seeded on small size flat or hollow fiber polyethersulfone (PES) membranes. Here, an upscaled "living membrane" is presented. We developed and assessed the functionality of modules containing three commercially available MicroPES HFM supporting ciPTEC. The HFM were optimally coated with L-Dopa and collagen IV to support a uniform and tight monolayer formation of matured ciPTEC under static culturing conditions. Both abundant expression of zonula occludens-1 (ZO-1) protein and limited diffusion of FITC-inulin confirm a clear barrier function of the monolayer. Furthermore, the uptake of 4-(4-(dimethylamino)styryl)-N methylpyridinium iodide (ASP+), a fluorescent OCT2 substrate, was studied in absence and presence of known OCT inhibitors, such as cimetidine and a cationic uremic solutes mixture. The ASP+ uptake by the living upscaled membrane was decreased by 60% in the presence of either inhibitor, proving the active function of OCT2. In conclusion, this study presents a successful upscaling of a living membrane with active organic cation transport as a support for BAK device. PMID- 27395801 TI - Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology. AB - In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20-30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed. PMID- 27395802 TI - Mapping the interactions and bioactivity of quercetin-(2-hydroxypropyl)-beta cyclodextrin complex. AB - Natural products have served as a rich source for drug discovery and development. In the last decade their fruitful integration in the drug discovery pipeline declined due to their reduced bioavailability, mainly attributed to their poor aqueous solubility. We synthesized a quercetin (QUE)-(2-hydroxypropyl)-beta cyclodextrin (HP-beta-CD) complex that enabled amplification of its solubility and in the same time retained its bioactivity in T24 human bladder cancer cell line. The stability of the complex and the molecular basis of the interactions developed in this host-guest complex were assayed by incorporating an array of analytical techniques and Molecular Dynamics (MD) experiments. 2D DOSY NMR experiment revealed that the diffusion coefficient of free HP-beta-CD was 3.55*10(-10)m(2)s(-1) while that of QUE-HP-beta-CD inclusion complex 3.09*10( 10)m(2)s(-1), indicating the formation of a complex. Solid and liquid high resolution NMR spectroscopy data showed that the most pronounced differences in chemical shifts at carbons and protons correspondingly during complexation occur in the aromatic ring Alpha (bearing the two phenolic hydroxyl groups meta to each other). The chemical shift differences in the aromatic ring Beta (bearing the two phenolic hydroxyl groups ortho to each other) were less pronounced. The MD results confirmed the experimental data. PMID- 27395804 TI - The effects of subchronic exposure to copper in fat snook (Centropomus parallelus). AB - Anthropogenic processes affect different communities through the release of contaminated effluents into water bodies. Copper can be found in the effluents of most industrial processes and in other effluent types. The fat snook Centropomus parallelus, found from Florida in the United States to southern Brazil, is of great economic importance and is used as a food resource near the coast. This study aimed to determine the effects of copper on C. parallelus. The fish were exposed for 30 or 60 days to treatments of 0, 13 and 26MUgCuL(-1). Genotoxic effects of copper were observed in the micronuclei, especially in individuals exposed to higher concentrations. Copper exposure also had a negative effect on the growth of fat snook individuals. Compared to the control group without the addition of metal, an accumulation of metal was observed in the gills of exposed fish, an effect that was not found in the muscle. PMID- 27395803 TI - Copper-induced overexpression of genes encoding antioxidant system enzymes and metallothioneins involve the activation of CaMs, CDPKs and MEK1/2 in the marine alga Ulva compressa. AB - Transcriptomic analyses were performed in the green macroalga Ulva compressa cultivated with 10MUM copper for 24h. Nucleotide sequences encoding antioxidant enzymes, ascorbate peroxidase (ap), dehydroascorbate reductase (dhar) and glutathione reductase (gr), enzymes involved in ascorbate (ASC) synthesis l galactose dehydrogenase (l-gdh) and l-galactono lactone dehydrogenase (l-gldh), in glutathione (GSH) synthesis, gamma-glutamate-cysteine ligase (gamma-gcl) and glutathione synthase (gs), and metal-chelating proteins metallothioneins (mt) were identified. Amino acid sequences encoded by transcripts identified in U. compressa corresponding to antioxidant system enzymes showed homology mainly to plant and green alga enzymes but those corresponding to MTs displayed homology to animal and plant MTs. Level of transcripts encoding the latter proteins were quantified in the alga cultivated with 10MUM copper for 0-12 days. Transcripts encoding enzymes of the antioxidant system increased with maximal levels at day 7, 9 or 12, and for MTs at day 3, 7 or 12. In addition, the involvement of calmodulins (CaMs), calcium-dependent protein kinases (CDPKs), and the mitogen activated protein kinase kinase (MEK1/2) in the increase of the level of the latter transcripts was analyzed using inhibitors. Transcript levels decreased with inhibitors of CaMs, CDPKs and MEK1/2. Thus, copper induces overexpression of genes encoding antioxidant enzymes, enzymes involved in ASC and GSH syntheses and MTs. The increase in transcript levels may involve the activation of CaMs, CDPKs and MEK1/2 in U. compressa. PMID- 27395805 TI - Brief intensive CBT for pediatric OCD with E-therapy maintenance. AB - Cognitive behaviour therapy (CBT), incorporating exposure and response prevention (ERP), has received strong empirical support for the treatment of paediatric OCD, and moreover, is considered the first line treatment of choice (Geller & March, 2012). However, despite the availability of effective treatments for this chronic and debilitating disorder, only a small proportion of youth receive these evidence-based approaches. The present study aimed to examine the effectiveness of an intensive ERP-based treatment for youth OCD, using a multiple baseline controlled design. Children and youth (N=10; aged 11-16 years) with a primary diagnosis of OCD were randomly assigned to a 1- or 2-week baseline monitoring condition followed by the intervention. The efficacy of the intensive treatment, involving 1 session psychoeducation, 2-sessions ERP plus e-therapy maintenance was examined across parent- child- and clinician-rated measures at post-treatment and 6-month follow-up. Overall, there were significant reductions across time on almost all measures (except self-report anxiety), and moreover, the majority of the sample (80%) were considered reliably improved, and meeting clinically significant change. At post-treatment, 60% were in remission of symptoms, and at 6-month follow-up this increased to 70%. These findings provide strong support for intensive, time-limited approaches to ERP-based CBT for children and youth with OCD. PMID- 27395806 TI - An integrative network approach to social anxiety disorder: The complex dynamic interplay among attentional bias for threat, attentional control, and symptoms. AB - Cognitive models posit that social anxiety disorder (SAD) is associated with and maintained by biased attention allocation vis-a-vis social threat. However, over the last decade, there has been intense debate regarding whether AB in SAD results from preferential engagement with or difficulty in disengaging from social threat. Further, recent evidence suggests that AB may merely result from top-down attentional impairments vis-a-vis non-emotional material. Consequently, uncertainty still abounds regarding both the relative importance and the mutual interactions of these different processes and SAD symptoms. Inspired by novel network approaches to psychopathology that conceptualize symptoms as complex dynamic systems of mutually interacting variables, we computed weighted directed networks to investigate potential causal relations among laboratory measures of attentional components and symptoms of social anxiety disorder. Global and local connectivity of network structures revealed that the three most central variables were the orienting component of attention as well as both avoidance and fear of social situations. Neither preferential attention engagement with threat nor difficulty disengaging from threat exhibited high relative importance as predictors of symptoms in the network. Together, these findings suggest the value of extending the network approach beyond self-reported clinical symptoms to incorporate process-level measures from laboratory tasks to gain new insight into the mechanisms of SAD. PMID- 27395807 TI - Endovascular Treatment of a Complex Renal Artery Aneurysm Using Coils and the Pipeline Embolization Device in a Patient with a Solitary Kidney. AB - BACKGROUND: We report a case of endovascular treatment of a complex renal artery aneurysm using the Pipeline Embolization Device, a flow diverting stent which is indicated for the treatment of large and giant cerebral aneurysms. METHODS: A forty-year-old female with medically refractory hypertension and congenital agenesis of the right kidney was found to have a 2.8-cm left superior renal artery branch aneurysm. The patient was treated successfully using the Pipeline Embolization Device (Medtronic, Irvine, CA) with coil embolization of the aneurysm and of one outflow vessel. RESULTS: On 3-year follow-up, her renal function was normal, vascular imaging showed complete occlusion of the aneurysm, and physiological remodeling of the reconstructed artery and parenchymal imaging showed no evidence of renal infarction. CONCLUSION: Flow diverting stents are a valuable treatment option for visceral aneurysms with complex anatomy. PMID- 27395808 TI - Perioperative Embolization Load and S-100beta Do Not Predict Cognitive Outcome after Carotid Revascularization. AB - BACKGROUND: Cognitive changes after carotid revascularization have been reported in 10-20% of patients. The etiology of cognitive impairments remains largely unknown. This study evaluates the predictive value of S-100beta serum values and perioperative microembolization on cognition after carotid revascularization. METHODS: Forty-six patients with significant carotid stenosis underwent carotid endarterectomy (CEA, n = 26), transfemoral carotid artery stenting with distal protection (CASdp, n = 10), or transcervical carotid stenting with dynamic flow reversal (CASfr, n = 10). Twenty-six matched vascular patients without carotid stenosis were recruited as controls. All patients underwent comprehensive cognitive testing on the day before and 1 month after carotid revascularization. S-100beta analysis was performed in 31 cases pre-, peri-, and 2, 6, and 24 hr after carotid surgery, and in 25 patients transcranial Doppler monitoring was done during surgery. RESULTS: In the 3 treatment groups similar transient increases in S-100beta values were observed. CASdp was associated with a higher embolic load than CEA and CASfr, while CEA was also associated with less microembolization than CASfr. Cognitive improvement or deterioration could not be predicted by S-100beta or perioperative embolic load for any of the investigated cognitive domains. CONCLUSIONS: Cognitive deterioration could not be predicted using perioperative embolic load and S-100beta changes. A similar inverted u curve of the S-100beta levels was observed in the 3 groups and may be caused by impairment in the blood-brain barrier during intervention, and not due to cerebral infarction. Distal protection CAS is associated with a higher embolic load than transcervical CAS using dynamic flow reversal and CEA, but the long term impact of this higher embolic load is yet unknown. Perfusion-related measures seem promising in their ability to predict cognitive decline. PMID- 27395809 TI - Increased Duration of Operating Time for Carotid Endarterectomy Is Associated with Increased Mortality. AB - BACKGROUND: Carotid endarterectomy is the gold standard operation to prevent stroke in patients with symptomatic carotid artery stenosis and asymptomatic high grade carotid artery stenosis. Longer operative times for different operations have been shown to affect the outcomes adversely. The purpose of this study was to determine the incidence of postoperative complications after carotid endarterectomy, and their relation to the operative times. METHODS: The American College of Surgeons database was queried for all patients who underwent carotid endarterectomies from 2005 to 2007. Patients were divided into 2 groups based on the operative time (<140 min and >140 min). The incidence of preoperative morbidities and postoperative complications was then compared among these groups. RESULTS: A total of 10,423 patients underwent carotid endarterectomies during this time period. Longer operative time (>140 min) is associated with higher incidence of 30-day mortality (1.3% vs. 0.7%, P = 0.013), length of stay >=7 days (12.7% vs. 8.1%, P < 0.001), postoperative pneumonias (1.6% vs. 0.9%, P = 0.001), failure to wean from ventilator for more than 48 hr (1.8% vs. 0.6%, P < 0.001), and return to the operating room (6.5% vs. 5.2%, P = 0.010). Factors associated with longer operative times were the following: age <65 years (odds ratio [OR] 1.3, confidence interval [CI] 1.1-1.6), male gender (OR 1.6, CI 1.4-1.7), black race (OR 1.5, CI 1.2-1.8), history of myocardial infarction (OR 1.7, CI 1.2-2.4), higher American Society of Anesthesiologist score (OR 1.3, CI 1.1-1.6), presence of surgical trainees (OR 3.6, CI 1.7-7.4), and presence of surgical fellows (OR 1.7, CI 1.4-2.2). CONCLUSIONS: Longer operative times for carotid endarterectomy are associated with increased risk of postoperative complications. Factors associated with longer operative times for carotid endarterectomy can be identified preoperatively. PMID- 27395810 TI - Pulmonary Artery Bullet Embolism following Cardiac Gunshot Wound. AB - Penetrating chest trauma is common but few need surgical treatment (10-20%). The mortality of gunshot wounds of the heart is 45%, among the wounded arriving at the hospital. The suspicion of wound heart with an inlet in the heart area (limited by costal awnings down, clavicles top, and mid-clavicular line outside) and pericardial effusion remains a surgical indication. Gunshot wounds of the heart with migration of the projectile in the pulmonary artery are rare. Migration of projectile into the pulmonary artery is described most often with lesions of peripheral veins without concomitant cardiac involvement. The indication of projectile extraction is not clearly defined in the literature. Conservative management of selected cases of pulmonary artery bullet emboli may be warranted in light of the risks of extraction. PMID- 27395811 TI - Impact of Endovascular Aortic Aneurysm Repair in a Renal Transplantation Program. AB - BACKGROUND: An increasing number of abdominal aortic aneurysms (AAAs) may occur in renal failure patients waiting for kidney transplantation because of sharing atherosclerotic risk factors. There is increasing possibility to diagnose an AAA in this group, where treatment has some particularities. After aneurysm treatment these patients remain candidates to kidney transplantation. Similarly, there is an increasing possibility to diagnose AAA in kidney transplantation recipients. Our aim is to present our experience and review the published literature. METHODS: We studied the patients who underwent endovascular aneurysm repair (EVAR) and were later submitted to kidney transplantation, and the patients who underwent kidney transplantation and were later diagnosed with AAA and treated by EVAR. RESULTS: Our experience with renal transplantation began in 1987 and with EVAR in 2001. We performed EVAR in 3 kidney transplantation recipients, without complications as endoleaks or loss of the transplanted kidney. We performed kidney transplantation in 2 patients who underwent EVAR. CONCLUSIONS: As patients waiting for kidney transplantation wait for several months to years, necessity to treat the aortic aneurysm is sometimes imperative. EVAR is the preferred method in this high-risk group with the particularity of necessity to preserve the internal/external iliac arteries to allow anastomosis between renal artery of the transplanted kidney and recipient's iliac artery. Ensuring this, kidney transplantation remains possible and we did not detect differences in comparison with a regular procedure. Kidney transplantation recipients have some particularities as immunosuppressive therapy; in this group, EVAR was recognized as less aggressive and with less impact in renal function. PMID- 27395812 TI - Endovascular Repair of a Right Subclavian Artery Aneurysm with Coil Embolization and Stent Graft: Case Report and Literature Review. AB - Subclavian artery aneurysms (SAAs) may be clinically asymptomatic or present with symptoms ranging from pain to upper limb ischemia, posterior circulation ischemia, or, most seriously, life-threatening rupture and hemorrhage. In recent years, endovascular treatment has been extensively employed as an alternative for treating SAAs with favorable anatomy, especially in patients who are not candidates for surgery. We report a case of successful endovascular treatment of SAA with coil embolization and stent graft. The follow-up examinations at 1 year showed good patency of the subclavian artery with no endoleak. PMID- 27395813 TI - The Rationale for Continuing Open Repair of Ruptured Abdominal Aortic Aneurysm. AB - BACKGROUND: Mortality after open repair of ruptured abdominal aortic aneurysms (RAAAs) remains high. The purpose of this study is to present the results of open RAAA treatment observing 2 different 10-year periods in a single high-volume center and to consider the possibilities of result improvement in the future. METHODS: Retrospective analysis of 729 RAAA patients who were treated through 1991-2001 (229 patients, Group A) and 2002-2011 (500 patients, Group B) was performed. Variables significantly associated with mortality were defined and analyzed. RESULTS: Overall 30-day mortality in Group A was 53.7% (123/229 patients) with intraoperative mortality of 13.5% (31/229 patients), while in Group B it was 37.4% (187/500 patients) with intraoperative mortality of 12.4% (62/500 patients). Overall 30-day mortality was significantly lower in Group B (P = 0.012). There was no difference regarding intraoperative mortality (P = 0.797). Preoperative severe hemodynamic instability (P < 0.01, P < 0.001), cardiac arrest (P < 0.01, P < 0.001), consciousness deterioration (P < 0.05, P < 0.001), renal malfunction (P < 0.01, P < 0.001), and significant anemia (P < 0.01, P < 0.001) were associated with increased mortality in both A and B groups, respectively. Aortic cross-clamping level in Group A was predominantly infrarenal (68%) while in Group B it was mostly supraceliac (53%) (P < 0.001). Cross-clamping time, duration of surgery, and type of aortic reconstruction had no influence on survival in Group B (P > 0.05). Intraoperative hemodynamic instability (P < 0.01, P < 0.001), significant bleeding (P < 0.05, P < 0.01), and low urine output (P < 0.05, P < 0.001) remained parameters that favored lethal outcome in both A and B groups, respectively. Cell saving was used only in Group B. The multivariate logistic regression applied on the complete sample of patients presented several significant predictors of lethal outcome: congestive heart failure on admission (odds ratio [OR] 1.954, 95% confidence interval [CI] 1.103-3.460), intraperitoneal rupture (OR 3.009, 95% CI 1.771-5.423), aortofemoral reconstruction (OR 1.928, 95% CI 1.044-3.563), and total operative time (OR 1.005, 95% CI 1.001-1.010). Postoperative multisystem organ failure (P < 0.01, P < 0.001), respiratory (P < 0.01, P < 0.001) and renal (P < 0.05, P < 0.001) failure, postoperative bleeding (P < 0.05), and cerebrovascular incidents (P < 0.05, P < 0.01) significantly increased mortality in both A and B groups. CONCLUSIONS: Although unselective, aggressive surgical approach in RAAA performed by teams experienced in open repair can improve patient's survival. Short admission/surgery time, supraceliac aortic cross-clamping, and the use of intraoperative cell saving are recommended. PMID- 27395814 TI - Conformability of GORE Excluder Iliac Branch Endoprosthesis and COOK Zenith Bifurcated Iliac Side Branched Iliac Stent Grafts. AB - BACKGROUND: Forty percent of the abdominal aortic aneurysms present an extension to the iliac axes. The access to a distal neck requiring an embolization of the internal iliac artery (IIA) may cause buttock claudication, colic ischemia, perineal necrosis, erectile dysfunction, and spinal cord ischemia. The aim of the branched iliac stent grafts is to preserve pelvic vascularization while adapting to the constraints of arterial tortuosity which generate type Ib endoleaks, plications, and limb thromboses. The objective was to analyze and compare the in vivo anatomical conformability of the Gore Excluder(r) Iliac Branch Endoprosthesis (IBE) and the Zenith Bifurcated Iliac Side(r) (ZBIS) Cook Iliac Endovascular Device branched stent grafts. METHODS: This was a monocentric retrospective therapeutic study including 13 IBE and 9 ZBIS stent grafts. Three indices of tortuosity were measured with EndoSize: common iliac artery, pelvic artery index (PAI), and the double iliac sign (DIS). The centerline lengths of the iliac axes and the iliac axis and the IIA were measured by 2 different operators as a blind fashion. RESULTS: The interoperator correlation of the measurements was r = 0.841 (P < 0.0001). Twenty-two patients had a high iliac tortuosity: PAI >= 1.14 (mean PAI 1.43 [1.16-2.09]). The IBE stent graft modified neither the ipsilateral length nor tortuosity of the common iliac axis or the PAI (P <= 0.17, P <= 0.16, and P <= 0.23, respectively). The ZBIS stent graft significantly modified (P <= 0.02) the length and the tortuosity measured by the PAI compared with the IBE group (P <= 0.02). The use of IBE or ZBIS did not modify the postoperative length of the IIA (P <= 0.34). Three patients of the IBE group presented one DIS. Postoperatively, they did not present any DIS without significant modification of the postoperative PAI (P <= 0.07). CONCLUSIONS: In patients with a severe iliac tortuosity, the IBE Gore branched iliac stent graft is more conformable than the ZBIS Cook. IBE, more conformable with the anatomy of the patient, could thus make it possible to decrease the incidence of distal endoleaks without increasing the risk of limb thrombosis related to the anatomical constraints. PMID- 27395815 TI - Management of a Thoracic Aortic Aneurysm during Pregnancy Leading to the Diagnosis of Takayasu Arteritis. AB - Takayasu arteritis is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. We report the case of a patient presenting with the rapid growth of a thoracic aortic aneurysm during pregnancy leading to the diagnosis of Takayasu disease and treated by a rapid delivery by cesarean section followed by an open aortic repair. One year after the operation the patient and her baby are alive and well. PMID- 27395816 TI - Successful Treatment of a Ruptured Extracranial Vertebral Artery Aneurysm with Onyx Instillation. AB - The rupture of an extracranial vertebral artery aneurysm has only been rarely described in the literature and treatment options are therefore not standardized. Here we report the successful endovascular repair of a spontaneously ruptured extracranial left vertebral artery aneurysm using Onyx instillation. A 48-year old woman was transferred to our clinic after having been intubated due to a massive hematoma of the left neck. A contrast-enhanced computed tomography (CT) showed a rupture of the left extracranial vertebral artery. Several issues complicated the therapeutic decision making in this rare case: first, the patient showed multiple aneurysms in CT angiography; therefore a connective tissue disease could not be excluded. Furthermore, as anamnestic work-up revealed that several episodes of postoperative bleeding and open surgery at this anatomic location are rarely performed, risks for postoperative complications were high. Therefore, the patient was hemodynamically stabilized and the ruptured aneurysm was treated in an endovascular approach with Onyx instillation and coil embolization. Complete exclusion of the aneurysm was achieved without periprocedural or neurological complications. Successful repair was confirmed by CT angiography on the first postoperative day as well as 12 months after the intervention. In conclusion, this case shows that endovascular Onyx embolization of ruptured vertebral aneurysms is a save and feasible method. PMID- 27395817 TI - Antimony release from contaminated mine soils and its migration in four typical soils using lysimeter experiments. AB - Antimony (Sb) can pose great risks to the environment in mining and smelting areas. The migration of Sb in contaminated mine soil was studied using lysimeter experiments. The exchangeable concentration of soil Sb decreased with artificial leaching. The concentrations of Sb retained in the subsoil layers (5-25cm deep) were the highest for Isohumosol and Ferrosol and the lowest for Sandy soil. The Sb concentrations in soil solutions decreased with soil depth, and were adequately simulated using a logarithmic function. The Sb migration pattern in Sandy soil was markedly different from the patterns in the other soils which suggested that Sb may be transported in soil colloids. Environmental factors such as water content, soil temperature, and oxidation-reduction potential of the soil had different effects on Sb migration in Sandy soil and Primosol. The high Fe and Mn contents in Ferrosol and Isohumosol significantly decreased the mobility of Sb in these soils. The Na and Sb concentrations in soils used in the experiments positively correlated with each other (P<0.01). The Sb concentrations in soil solutions, the Sb chemical fraction patterns, and the Sb/Na ratios decreased in the order Sandy soil>Primosol>Isohumosol>Ferrosol, and we concluded that the Sb mobility in the soils also decreased in that order. PMID- 27395819 TI - Potential drugs for the management of patients with takotsubo syndrome. PMID- 27395818 TI - Association of decreased serum vasostatin-2 level with ischemic chronic heart failure and with MACE in 3-year follow-up: Vasostatin-2 prevents heart failure in myocardial infarction rats. AB - BACKGROUND: We investigated whether serum vasostatin-2 level is related to chronic heart failure (CHF) in patients with previous myocardial infarction (MI) and MACE in 3-year follow-up. The biological effect of vasostatin-2 on ischemic HF was evaluated in animal experiments. METHODS: After exclusion of the subjects not eligible, this study included 450 patients with CHF and previous MI, and 149 healthy controls. Serum vasostatin-2 level was analyzed. CHF patients were followed up for three years and major adverse cardiac events (MACE) were recorded, defined as reinfarction, target-vessel revascularization, cardiovascular death and refractory HF requiring hospitalizations. RESULTS: Notably, serum vasostatin-2 level was decreased in CHF patients than in controls, and significant difference was observed between CHF patients with MACE and those without (both P<0.05). Vasostatin-2 level was correlated with HF stages (Spearman's r=-0.288, P<0.05), LVEF (r=0.377, P<0.05) and pro-BNP level (r= 0.294, P<0.05). Multivariable logistic regression analysis suggested that vasostatin-2, conventional risk factors, severity of HF stages and LVEF were independently associated with MACE in CHF patients. Vasostatin-2 (100MUg) or PBS was injected intraperitoneally every other day in MI rats, follow by echocardiography, hemodynamic analysis after 2months. Compared with PBS, vasostatin-2 treatment prevented ischemic HF in MI rats, accompanied with reduction of infarct size, remodeling, fibrosis and inflammation, mainly through inhibition of Rho, Wnt and TLR-4 pathways and modulation of renin-angiotensin system. CONCLUSION: Decreased serum vasostatin-2 level is associated with ischemic CHF and with MACE in three-year follow-up. Intraperitoneal injection of vasostatin-2 protects against ischemic HF in MI rats. PMID- 27395820 TI - Severe left ventricular hypertrophy and marked cardiac fibrosis in Danon disease. PMID- 27395821 TI - Optimizing driving safety: It is a team sport. PMID- 27395822 TI - The profile of volatile compounds in the outer and inner parts of broiled pork neck is strongly influenced by the acetic-acid marination conditions. AB - Raw pork neck cutlets were marinated in an aqueous solution of acetic acid (pH4, 24h, 4 degrees C) without (M) or with 1% (w/w) of glucose. The control (K) was formed by non-treated raw pork neck. The cutlets were then broiled (185 degrees C, 30min). In all K cutlets, significant higher amounts of volatile compounds (VCs) were developed after broiling than the other samples. Significant more aldehydes and alcohols were present in the inner parts than in the surface. The correlation between surface and internal layers was high only for aldehydes. Marinating decreased the differences among VCs and led to the standardization of the processed meat. The addition of glucose to the marinade led to more volatile aldehydes, carboxylic acids, esters, furan, pyran, pyrazine, pyrrol and pyridine derivatives than in M samples. Several (53) specific VCs explained the differences among the surface samples related to the marinating process. However, only 16 VCs explained the variance among the inner parts. PMID- 27395823 TI - Two efficient nitrite-reducing Lactobacillus strains isolated from traditional fermented pork (Nanx Wudl) as competitive starter cultures for Chinese fermented dry sausage. AB - Lactic acid bacteria isolated from traditional Dong pork product (Nanx Wudl) were investigated for their potential as starter cultures for Chinese fermented dry sausages. Based on preliminary screening, Lactobacillus plantarum CMRC6 and Lactobacillus sakei CMRC15, both showing excellent nitrite-reducing capacity, were used as single-strain starter cultures. For comparison, a commercial composite starter was also tested. In CMRC6 and CMRC15-inoculated sausages, lactic acid bacteria dominated the microflora and improved the microbiological safety by suppression of Enterobacteriaceae growth. Nitrite content of all inoculated sausages declined rapidly during ripening compared to non-inoculated. Texture profiles analysis showed inoculated sausages had more pronounced textural development during ripening. Sensory evaluation indicated CMRC6 and CMRC15 fermented sausages had comparable or more desirable organoleptic characteristics than sausage made with commercial starters. Therefore, CMRC6 and CMRC15 are promising candidates as multi-functional starter cultures for microbiological safety and residual nitrite control in gourmet Chinese dry sausage production. PMID- 27395824 TI - Accuracy of dual energy X-ray absorptiometry (DXA) in assessing carcass composition from different pig populations. AB - The accuracy of dual energy X-ray absorptiometry (DXA) in assessing carcass composition from pigs with diverse characteristics was examined in the present study. A total of 648 pigs from three different sire breeds, two sexes, two slaughter weights and three different diets were employed. DXA estimations were used to predict the dissected/chemical yield for lean and fat of carcass sides and primal cuts. The accuracy of the predictions was assessed based on coefficient of determination (R(2)) and residual standard deviation (RSD). The linear relationships for dissected fat and lean for all the primal cuts and carcass sides were high (R(2)>0.94, P<0.01), with low RSD (<1.9%). Relationships between DXA and chemical fat and lean of pork bellies were also high (R(2)>0.94, P<0.01), with RSD <2.9%. These linear relationships remained high over the full range of variation in the pig population, except for sire breed, where the coefficient of determination decreased when carcasses were classified based on this variable. PMID- 27395825 TI - Emerging markets for imported beef in China: Results from a consumer choice experiment in Beijing. AB - The purpose of this study is to explore emerging markets for imported beef in China by assessing Beijing consumer demand for quality attributes. This study utilizes data from an in-store choice experiment to evaluate consumer willingness to-pay for select food quality attributes (food safety, animal welfare, Green Food and Organic certification) taking into account country-of-origin information. Our results show that Beijing consumers value food safety information the most, and are willing to pay more for Australian beef products than for US or domestic (Chinese) beef. We explore the various relationships between the quality attributes, find evidence of preference heterogeneity and discuss agribusiness and marketing implications of our findings. PMID- 27395826 TI - Characteristics of thoracic aortic aneurysm rupture in vitro. AB - Ascending thoracic aortic aneurysms (ATAAs) are focal dilatations in the aorta that are prone to rupture or dissection. To accurately evaluate the rupture risk, one must know the local mechanical conditions at the rupture site and understand how rupture is triggered in a layered fibrous media. A challenge facing experimental studies of ATAA rupture is that the ATAA tissue is highly heterogeneous; experimental protocols that operate under the premise of tissue homogeneity will have difficulty delineating the location conditions. In this work, we employed a previously established pointwise identification method to characterize wall stress, strain, and property distributions to a sub-millimeter resolution. Based on the acquired field data, we obtained the local mechanical properties at the rupture site in nine ATAA tissue samples. The rupture stress, ultimate strain, energy density, and the toughness of the tested samples were also reported. Our results show that the direction of the rupture is aligned with the direction of maximum stiffness, indicating that higher stiffness is not always related to higher strength. It was also found that the rupture generally occurs at a location of highest stored energy. As a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the recruitment of collagen fibers in the deformation of the tissue is probably essential in ATAA rupture. STATEMENT OF SIGNIFICANCE: A major challenge in the experimental study of aneurysm properties is that the tissues are heterogeneous. When the specimens are not reasonably homogeneous, traditional tests that work under the premise of tissue homogeneity cannot reliably delineate the local conditions at the rupture site. In this work, we investigated the local characteristics of rupture of human ascending aortic aneurysm tissue. We identified the stress, strain, and elastic properties to a submillimeter resolution. Based on the field values, we determined the local conditions - elastic properties, direction of maximum stiffness, stress, strain, energy consumption - at the rupture site. It was found that the tissues consistently cleave in the direction of the maximum stiffness, and generally occurs at the location of highest energy. Since a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the work suggests that the recruitment of collagen fibers in the deformation of the tissue is probably essential in aneurysm rupture. PMID- 27395827 TI - A novel method for isolation and recovery of ceramic nanoparticles and metal wear debris from serum lubricants at ultra-low wear rates. AB - Ceramics have been used to deliver significant improvements in the wear properties of orthopaedic bearing materials, which has made it challenging to isolate wear debris from simulator lubricants. Ceramics such as silicon nitride, as well as ceramic-like surface coatings on metal substrates have been explored as potential alternatives to conventional implant materials. Current isolation methods were designed for isolating conventional metal, UHMWPE and ceramic wear debris. In this paper, we describe a methodology for isolation and recovery of ceramic or ceramic-like coating particles and metal wear particles from serum lubricants under ultra-low and low wear performance. Enzymatic digestion was used to digest the serum proteins and sodium polytungstate was used as a novel density gradient medium to isolate particles from proteins and other contaminants by ultracentrifugation. This method demonstrated over 80% recovery of particles and did not alter the size or morphology of ceramic and metal particles during the isolation process. STATEMENT OF SIGNIFICANCE: Improvements in resistance to wear and mechanical damage of the articulating surfaces have a large influence on longevity and reliability of joint replacement devices. Modern ceramics have demonstrated ultra-low wear rates for hard-on-hard total hip replacements. Generation of very low concentrations of wear debris in simulator lubricants has made it challenging to isolate the particles for characterisation and further analysis. We have introduced a novel method to isolate ceramic and metal particles from serum-based lubricants using enzymatic digestion and novel sodium polytungstate gradients. This is the first study to demonstrate the recovery of ceramic and metal particles from serum lubricants at lowest detectable in vitro wear rates reported in literature. PMID- 27395828 TI - Macrophage reaction against biomaterials in the mouse model - Phenotypes, functions and markers. AB - The foreign body reaction (FBR) is a response of the host tissue against more or less degradation-resistant foreign macromolecular material. The reaction is divided into five different phases which involve most aspects of the innate and the adaptive immune system: protein adsorption, acute and chronic inflammation, foreign body giant cell formation and fibrosis. It is long known, that macrophages play a central role in all of these phases except for protein adsorption. Initially it was believed that the macrophage driven FBR has a complete negative effect on biocompatibility. Recent progress in biomaterial and macrophage research however describe macrophages as more than pure antigen phagocytosing and presenting cells and thus pro-inflammatory cells involved in biomaterial encapsulation and failure. Quite contrary, both, pro-inflammatory M1 macrophages, the diverse regulatory M2 macrophage subtypes and even foreign body giant cells (FBGC) are after necessary for integration of non-degradable biomaterials and degradation and replacement of degradable biomaterials. This review gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of biomaterials is shortly discussed. STATEMENT OF SIGNIFICANCE: The view on role of macrophages in the foreign body reaction against biomaterials is rapidly changing. Despite the initial idea that macrophage are mainly involved in undesired degradation and biomaterial rejection it becomes now clear that they are nevertheless necessary for proper integration of non-degradable biomaterials and degradation of placeholder, degradable biomaterials. As a pathologist I experienced a lack on a good summary on the current taxonomy, functions and phenotypes of macrophages in my recent projects on the biocompatibility of biomaterials in the mouse model. The submitted review therefore intends to gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of biomaterials is shortly discussed. PMID- 27395829 TI - Engineering of caveolae-specific self-micellizing anticancer lipid nanoparticles to enhance the chemotherapeutic efficacy of oxaliplatin in colorectal cancer cells. AB - Novel nanomaterials for the intracellular transport of therapeutic cargos have been actively sought to effectively breach cell-membrane barriers. In this study we developed novel self-micellizing anticancer lipid (SMAL)-based pro-apoptotic nanoparticles (NPs) that enhance the accumulation and chemotherapeutic efficacy of oxaliplatin (OL) in colorectal cancer cells (CRCs). We demonstrated that NPs with special affinity to caveolae could be designed and based on this specificity, NPs effectively differentiated between endothelial cells (tumor cells) and epithelial cells, without the need for a cell-specific targeting moiety. We demonstrated a remarkable uptake of OL-loaded SMAL NPs (SMAL-OL) in HCT116 and HT-29 cells via the caveolae-mediated endocytosis (CvME) pathway. The higher accumulation of SMAL-OL in the intracellular environment resulted in a significantly elevated anticancer effect compared to that of free OL. Cell cycle analysis proved G2/M phase arrest, along with substantial presence of cells in the sub-G1 phase. An immunoblot analysis indicated an upregulation of pro apoptotic markers (Bax; caspase-3; caspase-9; and PARP1) and downregulation of Bcl-xl and the PI3K/AKT/mTOR complex, indicating a possible intrinsic apoptotic signaling pathway. Overall, the ability of SMAL NPs to confer preferential specificity towards the cell surface domain could offer an exciting means of targeted delivery without the need for receptor-ligand-type strategies. STATEMENT OF SIGNIFICANCE: In this work, we developed a novel self-micellizing anticancer lipid (SMAL)-based pro-apoptotic nanoparticles (NPs) that enhance the accumulation and chemotherapeutic efficacy of oxaliplatin (OL) in colorectal cancer cells. We demonstrated that NPs with special affinity to caveolae could be realized and based on this specificity, NPs effectively differentiated between endothelial cells (tumor cells) and epithelial cells, without the need for a cell specific targeting moiety. In addition, oxaliplatin-loaded SMAL were efficiently endocytosed by the cancer cells and represent a significant breakthrough as an effective drug delivery system with promising potential in cancer therapy. We believe this work holds promising potential for the development of next generation of multifunctional nanocarriers for an exciting means of targeted delivery without the need for receptor-ligand-type strategies. PMID- 27395830 TI - Functional inhibition of Hsp70 by Pifithrin-MU switches Gambogic acid induced caspase dependent cell death to caspase independent cell death in human bladder cancer cells. AB - Heat shock protein-70kDa (Hsp70) is a member of molecular chaperone family, involved in the proper folding of various proteins. Hsp70 is important for tumor cell survival and is also reported to be involved in enhancing the drug resistance of various cancer types. Hsp70 controls apoptosis both upstream and downstream of the mitochondria by regulating the mitochondrial membrane permeabilization (MMP) and apoptosome formation respectively. In the present study, we have elucidated the role of Hsp70 in Gambogic acid (GA) induced apoptosis in bladder cancer cells. We observed that functional inhibition of Hsp70 by Pifithrin-MU switches GA induced caspase dependent (apoptotic) cell death to caspase independent cell death. However, this cell death was not essentially necrotic in nature, as shown by the observations like intact plasma membranes, cytochrome-c release and no significant effect on nuclear condensation/fragmentation. Inhibition of Hsp70 by Pifithrin-MU shows differential effect on MMP. GA induced MMP and cytochrome-c release was inhibited by Pifithrin-MU at 12h but enhanced at 24h. Pifithrin-MU also reverted back GA inhibited autophagy which resulted in the degradation of accumulated ubiquitinated proteins. Our results demonstrate that Hsp70 plays an important role in GA induced apoptosis by regulating caspase activation. Therefore, inhibition of Hsp70 may hamper with the caspase dependent apoptotic pathways induced by most anti-cancer drugs and reduce their efficacy. However, the combination therapy with Pifithrin-MU may be particularly useful in targeting apoptotic resistant cancer cells as Pifithrin-MU may initiate alternative cell death program in these resistant cells. PMID- 27395831 TI - Reversible Cerebral Atrophy in Infantile Tremor Syndrome. AB - BACKGROUND: We report changes in MRI brain of children with Infantile Tremor Syndrome (ITS) at the onset of illness and following treatment. CASE CHARACTERISTICS: Three children with infantile tremor syndrome were assessed for changes in brain neuroimaging at admission and at follow-up visit. On MRI, all children had mild to severe diffuse cerebral atrophy, which reverted back to normal on follow-up visits. OUTCOME: Children with infantile tremor syndrome have reversible diffuse cerebral atrophy on neuroimaging. PMID- 27395832 TI - Hansens Chronic Polyarthritis in a Child. AB - BACKGROUND: Musculoskeletal manifestations of leprosy are often underdiagnosed and under-reported. CASE CHARACTERISTICS: An 11-year old girl with leprosy presented with deforming symmetric polyarthritis with raised inflammatory parameters and erosion on imaging. OBSERVATION: The patient was diagnosed to have Hansens chronic polyarthritis and treatment started with non-steroidal anti inflammatory drugs and methotrexate. MESSAGE: Hansen chronic polyarthritis is a rare differential of juvenile chronic arthritis in children. PMID- 27395833 TI - Health Related Quality of Life in Patients with Transfusion-dependent Thalassemia. AB - Patients with transfusion-dependent thalassemia are expected to have an unfavorable quality of life due to multiple factors. We studied the quality of life in 72 patients (age 5-39 y) with transfusion-dependent thalassemia in the era of improved care, and assessed different parameters affecting it. PMID- 27395834 TI - Metabolic Liver Diseases Presenting as Acute Liver Failure in Children. AB - CONTEXT: Suspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour. EVIDENCE ACQUISITION: Data over the last 15 years was searched through Pubmed using the keywords Metabolic liver disease and Acute liver failure with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review. RESULTS: Metabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilsons disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly. CONCLUSION: A high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of lifesaving therapy. PMID- 27395835 TI - Peptic Ulcers and Erosions in Children at a Pediatric Unit in Turkey. AB - OBJECTIVE: To study the characteristics of peptic ulcer and erosion in pediatric patients. METHODS: Over a period of seven years, 1,026 children underwent upper gastrointestinal endoscopy in our pediatric gastroenterology unit. RESULTS: Peptic ulcers and erosions were found in 59 (7.2%) patients [ulcers in 42 (5.1%)and erosions in 17 (2.1%)]. Thirty (50.9%) children presented with acute upper gastrointestinal bleeding. Helicobacter pylori positivity was found in 27 patients (45.8%), and ulcerogenic medication use was found in 13 (22%) patients. CONCLUSION: The main risk factors for childhood peptic ulcer and erosions were H. pylori infection and non-steroidal anti-inflammatory drug use. PMID- 27395836 TI - Outcome of Gaucher Disease in India: Lessons from Prevalent Diagnostic and Therapeutic Practices. AB - OBJECTIVE: To study disease severity and response to enzyme replacement therapy in Gaucher disease. METHODS: Updated data was captured from records of 37 patients (35 reported previously) with confirmed diagnosis of Gaucher disease from January 1995 through December 2011 (31, 83.8 %) and prospectively from January 2012 through June 2013 (6, 16.2 %). Severity of manifestations was determined by Gaucher disease Severity Score Index. Response to enzyme replacement therapy was assessed in terms of attainment of therapeutic goals. RESULTS: Moderate to severe manifestations (domain score of > 2) were observed in treated patients at baseline (83%, 58%, 66% and 25% for anemia, thrombocytopenia, hepatomegaly and leucopenia, respectively and 100% for splenomegaly and elevated plasma chitotriosidase). None of the 11 patients treated with synthetic enzyme (average annual dose 23 to 53 units/kg) attained all therapeutic goals in the recommended time frame, particularly the visceral, skeletal and growth domains. CONCLUSION: Early onset of moderate to severe disease in Indian patients mandates early therapy with optimum doses to ensure attainment of all recommended therapeutic goals. PMID- 27395837 TI - Prevalence of Obesity and Overweight Among School Children Aged 8-18 Years in Rajkot, Gujarat. AB - A total of 1496 school children aged 8-18 years (79.1% boys) participated in this study. Prevalence of obesity and overweight was estimated by using three different growth standards. Revised IAP 2015 growth standards detected more obese and overweight children than WHO 2007 and IOTF standards. PMID- 27395838 TI - Assessment of Iodine Deficiency in School Children in Aligarh District, India. AB - We carried out the study to assessw iodine deficiency disorders among school children of 6-12 years age group in Aligarh district of India. The prevalence of goiter was 5.2%. Modern Urinary Iodine Excretion level was 150 MUg/l, 22.5% of students had biochemical iodine deficiency. 50.4% households were consuming adequately iodized salt. PMID- 27395839 TI - Evaluation of Knowledge and Skills of Home Based Newborn Care among Accredited Social Health Activists (ASHA). AB - OBJECTIVE: We assessed the knowledge level and skills of trained ASHAs in providing home-based newborn Care. METHODS: 100 ASHAs from two talukas of Anand district of Gujarat participated. Knowledge was assessed using a structured questionnaire while certain skills were assessed through direct observation on mannequine. RESULTS: The mean (SD) knowledge score of the participants was 16.7(3.16) out of 34. The skills were satisfactory in 52%, 61%, 43%, and 68% of ASHA workers for temperature measurement, hand washing, weight measurement and skin-to-skin care, respectively. Huge variability was observed in self reported field performance of ASHAs. CONCLUSION: knowledge and skills of Asha works in this region were inadequate. PMID- 27395840 TI - Application of the International Classification of Functioning, Disability and Health - Children and Youth in Children With Cerebral Palsy. AB - The International Classification of Functioning, Disability and Health (ICF) is a framework for describing health status; however, there is a gap in literature for supporting its use as a classification tool. The purpose of this paper is to provide a perspective on its use in describing children with cerebral palsy. The interconnected concepts of the ICF are more important than the classification elements itself. Further research is required to prove its use as a classification tool in clinical practice. PMID- 27395841 TI - A partial revision of the Australian Eulimnadia Packard, 1874 (Branchiopoda: Spinicaudata: Limnadiidae). AB - The worldwide genus Eulimnadia previously with only five species described from Australia, is known now to have at least 15 endemic species plus about 10 undescribed species detected by molecular means. Most have variable morphological features, though each has a distinctive resting egg morphology. Many occur in the known branchiopod hot spot of the Paroo/Bulloo catchments in western New South Wales and Queensland. Some are specific to gnammas (rock holes). Given the rarity of males, androdioecious reproduction is probable in most species. Keys are provided for all known Australian species. PMID- 27395842 TI - The importance of tracking introduced species: nine synonyms of Atheta (Dimetrotina) pasadenae Bernhauer, 1906 (Coleoptera, Staphylinidae, Aleocharinae). AB - Five species names are placed in synonymy with Atheta (Dimetrotina) pasadenae Bernhauer, 1906: Dimetrota vaniuscula Casey, 1911; Atheta pseudocoriaria Bernhauer, 1943 (non Cameron, 1939); A. zealandica Cameron, 1945; A. aucklandensis Pace, 1987 and A. pseudoinsulana Klimaszewski in Klimaszewski et al., 2002. Four names are confirmed to be junior synonyms of A. pasadenae: Atheta pseudolaticollis Erber & Hinterseher, 1992 (non Bernhauer, 1936, non Cameron, 1944); A. immucronata Pace, 1999; A. gulosa Tronquet, 2000 and A. atlantidum Smetana, 2004. Lectotypes are designated for A. pseudocoriaria Bernhauer, 1943; A. zealandica Cameron, 1945 (both designations are to be attributed to Richard A.B. Leschen); and A. pasadenae Bernhauer, 1906. Relationships among the subgenera Xenota Mulsant & Rey, 1874, Dimetrotina Casey, 1911, Oxypodera Bernhauer, 1915 and Mycetota Adam, 1987 of the genus Atheta Thomson, 1858 are discussed. The name Mycetota Adam, 1987 is placed in synonymy with Dimetrotina Casey, 1911 (treated as valid subgenus of Atheta), resulting in three new subgeneric assignments: Atheta (Dimetrotina) laticollis (Stephens, 1832), A. (D.) mucronata (Kraatz, 1859), and A. (D.) pasadenae Bernhauer, 1906. Atheta pasadenae is a species with almost cosmopolitan distribution, most likely originating from Africa and (unintentionally) introduced to Europe, North and South America, New Zealand, the Macaronesian islands, Tristan da Cunha archipelago, Juan Fernandez archipelago and Hawaii. PMID- 27395843 TI - Complete larval development of Thor amboinensis (De Man, 1888) Decapoda: Thoridae) described from laboratory-reared material
and identified by DNA barcoding. AB - Of the 12 species of Thor described until present date, only three (25%) have their complete larval development known. Present work describes the complete larval development of Thor amboinensis, based on laboratory-reared material. The spent females were identified through the analysis of the partial sequences of the mitochondrial DNA barcode, also used for the reconstruction of the phylogenetic relationships within the recently resurrected and recognized family Thoridae Kingsley, 1879. Eight zoeal stages and one decapodid complete this species larval development. In the genus Thor, the number of zoeal stages varies greatly from two (T. dobkini) to eight (T. amboinensis and T. floridanus). The larvae of T. ambionensis and T. floridanus are readily distinguished from each other by the ornamentation of the ventral margin of the carapace and the pereiopods development. The first zoeal stage of T. amboinensis described by Yang & Okuno (2004) and the one described in present study are very similar. A brief discussion on the morphological characters and on the number of zoeal stages of the genus, as well as of the previous larval descriptions is made. The phylogenetic analysis suggest cryptic speciation for geographical separated populations of T. amboinensis, paraphyly of the genus Eualus, and the reassignment of E. cranchii to a different genus. PMID- 27395844 TI - A new small frog species of the genus Pristimantis (Anura: Craugastoridae) from the northern paramos of Colombia. AB - I describe a new species of a small-sized frog of the genus Pristimantis found in the paramo ecosystem (3700 masl) on the northern slope of Los Nevados National Park, Cordillera Central, department of Caldas, Colombia. This new species is assigned to the Pristimantis leptolophus species-group, given that Toe V is much longer than Toe III and extends to the distal edge of the distal subarticular tubercle on Toe IV. The new species differs from other taxa by its dorsal golden or yellowish color patterns, the absence of nuptial pads, lateral fringes on its fingers and toes, and the absence of vomerine odontophores. Discriminant analyses of morphometric characters of females of P. leptolophus, P. uranobates, and the new species separate the new species by snout-vent length, tibia length, eye diameter, eye-to-nostril distance, tympanum diameter, and length of toe III. Vomer terms frequently used to describe species are reviewed, such as the oblique keels of the vomer and the different forms of the dentigerous process. Species belonging to the high Andean Pristimantis leptolophus species-group are allopatric, suggesting vicariant speciation in different areas of the paramos. PMID- 27395845 TI - Review of the genus Eugryllacris Karny, 1937 (Orthoptera: Gryllacridinae)
from China. AB - The Chinese species of Eugryllacris are reviewed. One new combination and six new species from China are described: Eugryllacris cylindrigera (Karny, 1926) com. nov., Eugryllacris bifoliata Bian & Shi sp. nov., Eugryllacris elongata Bian & Shi sp. nov., Eugryllacris fanjingshanensis Bian & Shi sp. nov., Eugryllacris lobulis Bian & Shi sp. nov., Eugryllacris longifissa Bian & Shi sp. nov. and Eugryllacris xiei Bian & Shi sp. nov.. A key to the species of Eugryllacris from China and a distribution map are presented. This paper is based on the material from the collection of the Museum of Hebei University. PMID- 27395846 TI - Limnodrilus sulphurensis n. sp., from a sulfur cave in Colorado, USA, with notes on the morphologically similar L. profundicola (Clitellata, Naididae, Tubificinae). AB - A new species of the tubificine genus Limnodrilus is described and COI barcoded from Sulphur Cave and associated springs in Colorado, USA. The habitats are characterized by high sulfide concentrations. The new species, L. sulphurensis, is distinguished from all congeners by the elongate, nearly parallel teeth of chaetae in its anterior segments. It has a penis sheath resembling that of L. profundicola; consequently, museum specimens and new collections are examined here to resolve some of the taxonomic confusion surrounding that widespread, but uncommon species. PMID- 27395847 TI - Eusynnada, a resurrected genus of Ochyromerina (Coleoptera: Curculionidae: Curculioninae: Tychiini), with description of a second species from India and Thailand. AB - Eusynnada is resurrected as a valid genus of Ochyromerina and includes the type species E. plaxoides Heller and a related second new species, E. canariumi sp. nov., from Andaman Island (India) and Thailand. PMID- 27395848 TI - A new species of the predaceous midge genus Brachypogon Kieffer from the Neotropical Region and first description of the female of Brachypogon (Isohelea) cuacuahuitlus Huerta & Borkent (Diptera: Ceratopogonidae). AB - The predaceous midge genus Brachypogon Kieffer is presently known in Mexico by Brachypogon (Brachypogon) fuscivenosus (Lutz, 1914), B. (B.) bimaculatus Spinelli & Grogan, 1998, B. (B.) woodruffi Spinelli & Grogan, 1998 and B. (Isohelea) cuacuahuitlus Huerta & Borkent, 2005. In this contribution a new species, Brachypogon (Brachypogon) ginue, is described and illustrated from a male specimen collected in Tlanchinol, State of Hidalgo, Mexico. This new species belongs to the impar species group. The first description of the female of Brachypogon (Isohelea) cuacuahuitlus Huerta & Borkent is also provided. PMID- 27395849 TI - Hydrolutos piaroa sp.n. (Orthoptera: Anostostomatidae), a new semiaquatic Lutosini species from south-western Venezuelan lowland streams. AB - Hydrolutos piaroa, a new species of Lutosini (Orthoptera: Anostostomatidae) from Tobogan de la Selva (Puerto Ayacucho region, SW Venezuela) is described and figured. Inhabiting aquatic environment it represents an unusual orthopteran with sternal and pleural area covered by fine microtrichia, forming a plastron. This is the first known Hydrolutos species sampled in lowland streams of Venezuelan Guayana. PMID- 27395850 TI - A new species of Leptoderma Vaillant, 1886 (Osmeriformes: Alepocephalidae) from the Pacific coast of Central America. AB - A new species of Leptoderma Vaillant, 1886 is described from a single specimen trawled at 1368-1406 m depth off El Salvador, Central America, tropical eastern Pacific. Leptoderma ospesca n. sp. can be readily distinguished from its congeners by the following combination of characters: dermal papillae absent along the lateral line, pectoral-fin rays 6, pelvic-fin rays 5, pre-dorsal length 54.9% of SL, both dorsal and anal fins separated from the caudal fin, dorsal- and anal-fin rays long, procurrent caudal-fin rays numerous and extending far forward on caudal peduncle, caudal-fin rays 16, and total pre-ural vertebrae 60. A key to the species of the genus is presented. PMID- 27395851 TI - Taxonomic review of catsharks of the Scyliorhinus haeckelii group, with the description of a new species (Chondrichthyes: Carcharhiniformes: Scyliorhinidae). AB - Sharks of the genus Scyliorhinus from the southwestern Atlantic are reviewed; identification problems and taxonomic misinformation given in the literature are rectified. After extensive examination of the external and internal morphology of specimens collected mostly off southeastern and southern Brazil, Scyliorhinus besnardi Springer & Sadowsky, 1970 is placed in the synonymy of S. haeckelii (Miranda Ribeiro, 1907), which is thoroughly redescribed. Additionally, a new species, Scyliorhinus cabofriensis, sp. nov., is described from the state of Rio de Janeiro, distinguished from all southwestern Atlantic congeners by its color pattern, clasper and neurocranial morphology, and proportional measurements. A key to Scyliorhinus species occurring in the southwestern Atlantic is also provided. PMID- 27395852 TI - Description of a new species of Cosmolaelaps Berlese and the male of C. brevipedestra (Karg) from Iran, with notes on some other species of Cosmolaelaps Berlese (Acari: Laelapidae). AB - We describe a new species of mite, Cosmolaelaps malmiriensis sp. nov., based on morphological characters of the adult female. We also describe the male of C. brevipedestra (Karg, 1985) and re-describe its female. Gaeolaelaps angustiscutatus (Willmann, 1951), and Gymnolaelaps markewitschi (Pirianyk, 1959) are transferred into Cosmolaelaps. Cosmolaelaps acutiscutus Teng, 1982 and C. subacutiscutus Bai & Wang, 2005 appear to be junior synonyms of C. angustiscutatus. Cosmolaelaps confinisetarum Moreira et al., 2014 is synonymised with C. guttulata (Karg, 1978). PMID- 27395853 TI - A new species of Gryllotalpa mole cricket (Orthoptera: Gryllotalpidae: Gryllotalpinae) from Peninsular Malaysia. AB - A new species of Gryllotalpa mole cricket (Orthoptera: Gryllotalpidae) is described from Bukit Larut, Perak, Peninsular Malaysia: Gryllotalpa permai sp. n. Acoustic analysis of the male calling songs were also provided for Gryllotalpa permai sp. n. and the morphologically similar Gryllotalpa fulvipes. PMID- 27395854 TI - Description of two final stadium Onychogomphus larvae from Thailand (Odonata: Gomphidae). AB - The final stadium larvae of Onychogomphus castor Lieftinck and O. duaricus Fraser are described and illustrated for the first time based on reared specimens from Thailand. The taxonomic characteristics of the larvae of the genus Onychogomphus are discussed and summarized. The larva of O. castor differs from other Southeast Asian species in having distinct mid-dorsal spines on S2-9, divergent wing pads reaching S5, and lateral spines on S6-9. The larva of O. duaricus has a weakly swollen third antennal segment, with short blunt mid-dorsal spines on S2-9, divergent wing sheaths reaching the middle of S4, and lateral spines present on S7-9. PMID- 27395855 TI - Two new species of Eustigmaeus Berlese (Acari: Trombidiformes: Stigmaeidae) from Brazil, with a key to the American species. AB - Two new species of Eustigmaeus, E. piracicabensis Paktinat-Saeij & Bagheri sp. nov., and E. oliveirai Paktinat-Saeij & Bagheri sp. nov., are described based on females collected from soil, humus and moss in the Sao Paulo state, Brazil. Also, a key to the American Eustigmaeus species is provided. PMID- 27395856 TI - Gymnotus refugio, a new and endangered species of electric fish of the Gymnotus pantherinus species-group from southern Brazil (Gymnotiformes: Gymnotidae). AB - Gymnotus refugio, new species, is described from coastal rivers of Rio Grande do Sul and Santa Catarina states, Brazil. It is diagnosed from most species of the Gymnotus pantherinus species-group by the coloration pattern, further differing from G. pantherinus and G. capitimaculatus on the basis of morphometric and meristic characters. The new species represents the most meridional record of the G. pantherinus species-group. PMID- 27395857 TI - New species and records of the genus Geodromicus Redtenbacher, 1857 (Coleoptera: Staphylinidae: Omaliinae) from Taiwan. AB - Two new species of the genus Geodromicus Redtenbacher, 1857 from Taiwan are described and illustrated: G. philydroides sp. n. (Nantou Hsien) and G. taiwanensis sp. n. (Kaohsiung Hsien, Hualien Hsien). Additional material and a new synonymy for G. ohkurai (Hayashi, 1992) = G. ohkurai yushanensis (Hayashi, 1992), syn. nov. are proposed. A key to species known from Taiwan is given. PMID- 27395858 TI - YASER ADELDOOST, RAMIN HEYDARI & MAJID PEDRAM (2015) Morphological and molecular characterization of Tylencholaimellus persicus sp. n. (Dorylaimida: Tylencholaimellidae) from Iran. Zootaxa, 4040 (1): 074-082. PMID- 27395859 TI - A checklist of Recent non-marine ostracods (Crustacea: Ostracoda) from Thailand, including descriptions of two new species. AB - A checklist covering a total of 67 Recent non-marine ostracod species from Thailand, belonging to 33 genera and seven families (Cyprididae, Candonidae, Ilyocyprididae, Notodromadidae, Darwinulidae, Limnocytheridae, Loxoconchidae), is presented. Twenty-five of these are considered endemic to the Oriental region, 17 of which are Thai endemics. Two species (Hemicypris exiqua Broodbakker, 1983, and Notodromas sinensis Neal & Zhao, 1991) are new records for the Oriental region, and four species (Cypretta seurati Gauthier, 1929, Chrissia ceylonica (Daday, 1898), Chrissia formosa (Klie, 1938), and Dolerocypris fasciata (O.F. Muller, 1776)) are new record for Thailand. The most diverse subfamily in Thailand is the Cypricercinae, with 22 species. The most diverse genera are Strandesia Stuhlmann, 1888 (eight species), followed by Pseudostrandesia Savatenalinton & Martens, 2009 (seven species) and Stenocypris Sars, 1889 (five species). Other enigmatic groups and new taxa occur in the checklist, but these need to be described elsewhere in the future. For example, several species of Cypridopsinae Kaufmann, 1900, Cyclocypridinae Kaufmann, 1900, Candoninae Kaufmann, 1900 and other groups await description. Considering regional distributions based on frequency of occurrences, rare species constitute a large fraction, whereas very common species are minor elements. Most of the records were reported from the Northern and Northeastern parts of Thailand. Sampled habitat types ranged from ponds, (oxbow) lakes, swamps, reservoirs, springs, canals, rivers, rice fields, waterfalls, and damp leaf litter. Most of the Thai ostracod fauna exists in a wide range of habitats. A brief discussion on the distribution of described species is included with the list. Additionally, in the present contribution, we describe two new species, Dolerocypris sisaketensis n. sp. and Hungarocypris suranareeae n. sp., from the Northeastern part of Thailand. The main character of Dolerocypris sisaketensis n. sp. is the presence of a spine on the postero ventral part of the right valve; this feature sets it apart from other Dolerocypris species. Hungarocypris suranareeae n. sp. is the second species of this genus in Thailand and the third one in Southeast Asia. It is clearly distinguished from other Hungarocypris species by the serration on both valves. The genera Dolerocypris and Hungarocypris are briefly discussed and a key to the species of Hungarocypris is provided. PMID- 27395860 TI - Taxonomy of 'Euconnus complex'. Part VI. Status of Protoscydmus and
Euconnus subgenera Neonapochus, Paranapochus, and Filonapochus (Coleoptera, Staphylinidae, Scydmaeninae). AB - Examination of the type species of the genus Protoscydmus (Borneo) and subgenera of Euconnus: Neonapochus (Europe) and Paranapochus (Madagascar, Oriental) revealed that these taxa do not differ in any important characters from Euconnus (Napochus). Consequently, Protoscydmus, Neonapochus, and Paranapochus are placed as junior synonyms of Napochus, and Euconnus (Napochus) sabahensis (Franz) is placed as a new combination (ex Protoscydmus). Filonapochus (Madagascar) is maintained as a separate subgenus of Euconnus; it also belongs to taxa similar to Napochus. PMID- 27395861 TI - Ciliate protozoa of the forestomach of llamas (Lama glama) from locations
at different altitude in Argentina. AB - This study describes the diversity and concentration of the protozoal population from the forestomach of llamas in Argentina at three altitudinal locations. Protozoal diversity was studied in samples from eight llamas from Hurlingham (Buenos Aires, 43 m altitude), four from Tilcara (Jujuy, 2465 m altitude) and six llamas from Cieneguillas (Jujuy, 3800 m altitude). The total concentrations of protozoa in the forestomach contents were 7.9, 9.1 and 4.1 cells x 104 ml-1 in Hurlingham, Tilcara and Cieneguillas, respectively (P>0.05). Entodinium spp. represented 97.9, 92.3 and 71.4% of the protozoal community in Hurlingham, Tilcara and Cieneguillas, respectively, and the remaining protozoa belonged to the Eudiplodinium genus. Entodinium spp. were identified as E. caudatum (mostly morphotype dubardi), E. longinucleatum, E. parvum, E. bovis, E. exiguum, E. dubardi, and a minor presence of E. bimastus (in three animals) and E. ovibos (in one animal). In regards to the rest of protozoal species, Eudiplodinium maggii is the first reported host record for the genus in llamas. This species was present in the forestomach of 14 out of 18 llamas tested, and in one case it was the unique protozoal species. The vestibuliferids, Dasytricha and Isotricha were absent from the forestomach of llamas. Similarly, other species such as those from the Caloscolex genus, Diplodinium cameli and Entodinium ovumrajae, commonly found in Old World Camelids, were also absent from llamas. PMID- 27395862 TI - Two new species of Acrocephalomyia Ibanez-Bernal & Hernandez-Ortiz, 2012 from Brazil (Diptera: Ropalomeridae) and a key to known species. AB - Two new species of Acrocephalomyia Ibanez-Bernal & Hernandez-Ortiz (Diptera, Ropalomeridae) are described. The genus currently includes three species, the type species from Costa Rica, Acrocephalomyia zumbadoi Ibanez-Bernal & Hernandez Ortiz, and two new species from Brazil herein described, A. torulosa sp. nov., (State of Mato Grosso do Sul, Midwest) and A. pulchra sp. nov. (State of Amazonas, North). A key for the known species of Acrocephalomyia is given and characters of the male terminalia are described and discussed for the first time, with special attention to the "epiphallus". PMID- 27395863 TI - New Jurassic Hangingflies (Insecta: Mecoptera: Bittacidae) from Inner Mongolia, China. AB - A new bittacid genus, Composibittacus gen. nov., with two new species, C. bipunctatus gen. et sp. nov. and C. reticulatus sp. nov., and a new species of Orthobittacus Willmann 1989, O. maculosus sp. nov., are described from the latest Middle Jurassic Jiulongshan Formation of Daohugou, Inner Mongolia, China. Composibittacus gen. nov. has unique wing characters, such as five pterostigmal crossveins between R1 and R2 and R1 and R2+3 and an elongated pterostigma area, which distinguishes it from all other known genera in Bittacidae. Orthobittacus maculosus sp. nov. differs from other species of Orthobittacus by a combination of the following wing characters: M with six branches in forewings and hind wings, two crossveins between C and Sc, and two pterostigmal crossveins in the forewing. In addition, O. maculosus sp. nov. has light-colored or white spots on the fore- and hind wings. These new venational characters of Composibittacus gen. nov. and O. maculosus sp. nov. enhance our understanding of the diverse morphological characters of early hangingflies. Furthermore, based on the striking similarity of the wings of O. maculosus sp. nov. and Juracimbrophlebia ginkgofolia Wang, Labandeira, Shih & Ren 2012 (Cimbrophlebiidae), we propose that leaf mimesis and mutualism with ginkgo plants might have been present in the Bittacidae, as has been proposed in the Cimbrophlebiidae. PMID- 27395864 TI - Alburnoides diclensis (Actinopterygii: Cyprinidae), a new species of cyprinid fish from the upper Tigris River, Turkey. AB - Alburnoides diclensis sp. n. is described from the Tigris River drainages (Persian Gulf basin) in southeastern Anatolia, Turkey. It is distinguished by a combination of the following characters (none unique to the species): a poorly developed ventral keel between pelvic and anal fins, completely scaled or rarely without one scale in front of anus; head short (length 24-27% SL), its upper profile markedly convex on level of nostril; mouth terminal, with marked chin; lips equal to or upper lip slightly longer than lower lip; snout with rounded tip, its length equal to or greater than eye diameter but smaller than interorbital distance; body moderately deep (depth at dorsal-fin origin 25-30% SL); anal-fin depth 1.2-1.4, mean 1.3 times in HL; 48-53 lateral-line scales, 121/2-151/2 branched anal-fin rays; 41-42 total vertebrae, comprising 20-21 abdominal and 20-21 caudal vertebrae. PMID- 27395865 TI - A new species of the subterranean genus Stygobromus (Amphipoda: Crangonyctidae) from a cave spring in northern Florida, USA. AB - A relatively large, distinct new species of the subterranean amphipod crustacean genus Stygobromus (Amphipoda: Crangonyctidae) measuring 13 mm in length is described from Skipper Spring, a cave spring in the northwestern "panhandle" of Florida, USA. This is the first species of the genus described from the state of Florida where it is described from only 3 females. A fourth much smaller specimen of this species was collected from nearby Miller's Crossing Spring on Holmes Creek. All other stygomorphic amphipod species recorded from the state of Florida have been in the genus Crangonyx. PMID- 27395866 TI - A new species of Tricholabiodes Radoszkowski, 1885 (Hymenoptera: Mutillidae) from Saudi Arabia. AB - A new species, Tricholabiodes aldryhimi Soliman, sp. nov., with a posteromesal bifurcal sessile process on the third metasomal sternum is described and illustrated from Najd Region, Saudi Arabia. The new species looks like T. brothersi Lelej, 2010 in having a bifurcal process on S3 but differs from it mainly in colour and the shape of the genitalia. PMID- 27395867 TI - Annotated catalogue of the Phylinae (Heteroptera: Miridae) from the Korean Peninsula. AB - The subfamily Phylinae (Miridae) of the Korean Peninsula are catalogued. A total of 88 species are recorded from the Korean Peninsula. This catalogue is based on all available published and unpublished data, mostly representated by recent findings by Duwal in Korean region from 2010-2015. Phylus miyamotoi Yasunaga 1999 is found for the first time from the Korean Peninsula and several species such as Atractotomus morio Sahlberg 1883, Harpocera choii Josifov 1977, H. koreana Josifov 1977, Phylus coryloides Josifov & Kerzhner 1972, and Rubrocuneocoris quercicola Josifov 1987 are newly reported from South Korea in this study. All taxa in this study are arranged according to the latest revised classification of Phylinae by Schuh & Menard (2013). Also, color image of dorsal habitus of each available species is provided. PMID- 27395868 TI - Redescription of the genus Cheleocloeon Wuillot & Gillies 1993 (Ephemeroptera: Baetidae) with descriptions of three new species from Zambia and Uganda. AB - Revised characteristics of Cheleocloeon Wuillot & Gillies 1993 are given. This taxon occupies a separate position within Anteropatellata. The species described as Cheleocloeon mirandei Lugo-Ortiz & McCafferty 1997 and Cheleocloeon sigiense Gillies 2001, as well as the species originally described as Centroptilum falcatum Crass 1947, do not belong to Cheleocloeon. Three new species, Ch. clavifolium sp. n., Ch. lancetofolium sp. n. and C. truncifolium sp. n. from Zambia and Uganda are described based on larvae, subimagoes, imagoes of both sexes and eggs associated by rearing. Additional characteristics of Ch. yolandae Wuillot 1993, Ch. carinatum Wuillot 1993 and Ch. soldani Gattolliat & Sartori 2008 are given based on new material. Some species of Cheleocloeon without formal names are reported from Zambia and Uganda. PMID- 27395869 TI - On the genus Gonioctena Chevrolat (Coleoptera: Chrysomelidae: Chrysomelinae), with descriptions of seven new species from the Oriental region and Palaearctic China. AB - Seven new species of Gonioctena Chevrolat are described from the Oriental region and Palaearctic China: Gonioctena (Asiphytodecta) mausonensis sp. nov., G. (A.) oudai sp. nov., G. (Brachyphytodecta) arunensis sp. nov., G. (B.) mauroi sp. nov., G. (B.) medvedevi sp. nov., G. (Gonioctena) fujiana sp. nov. and G. (G.) mongolica sp. nov. Gonioctena (Asiphytodecta) subgeminata tonkinensis (Chen, 1934) is removed from synonymy with G. (A.) subgeminata (Chen, 1934) and raised to the species level. Gonioctena (Gonioctena) suwai Takizawa, 1985 is synonymized with G. (G.) ogloblini Medvedev & Dubeshko, 1972. Gonioctena (Asiphytodecta) sapaensis nom. nov. is proposed as a replacement name for G. (A.) unicolor Medvedev, 1987 not Phytodecta quinquepunctata var. unicolor Weise, 1884. Lectotype is designated for Phytodecta subgeminatus var. tonkinensis Chen, 1934. PMID- 27395870 TI - Cyrtodactylus rufford, a new cave-dwelling bent-toed gecko (Squamata: Gekkonidae) from Khammouane Province, central Laos. AB - We describe a new species of the gekkonid genus Cyrtodactylus from Khammouane Province, central Laos based on morphological and molecular data. Morphologically, Cyrtodactylus rufford sp. nov. differs from its congeners by a unique combination of the following characters: medium size, SVL reaching 72.5 mm; dorsal pattern with three or four light transverse bands between limb insertions; one intersupranasal; 14-16 irregular dorsal tubercle rows at midbody, weakly developed in the paravertebral region; 27-29 ventral scale rows between ventrolateral folds; 42-43 precloacal and femoral pores in a continuous row in males, enlarged femoral and precloacal scales present; 4 or 5 postcloacal tubercles on each side; dorsal tubercles present at base of tail; medial subcaudal scales enlarged. Molecular analyses show that the new species is closely related to C. khammouanensis, which was originally described from Khammouane Province. PMID- 27395871 TI - Steinernema goweni n. sp. (Rhabditida: Steinernematidae), a new entomopathogenic nematode from Zulia State, Venezuela. AB - A nematode from the genus Steinernema was isolated in Zulia state (North-western, Venezuela). Morphological, morphometric and molecular studies indicated that this nematode belongs to the "bicornutum" group and is described herein as Steinernema goweni n. sp. Steinernema goweni n. sp. is characterised by morphometrics of its infective juveniles, with body length 640 (531-719) um, pharynx length of 119 (109-126) um, tail of 67 (59-89) um, c ratio = 9 (6-11) and E% = 77 (48-94). First generation male specimens can be recognised by the shape and size of spicules (55 (50-57) um long) and gubernaculum (35 (30-40) um long), and %D value 42 (28-59), which is at the lower limit within the "bicornutum" group. The number of genital papillae in males is also distinctive for S. goweni n. sp. presenting up to 27 (13 pairs + 1) papillae in 15% of specimens. The phasmids can be seen in scanning electron microscopy in all stages, characters not previously reported within the "bicornutum" group. Phylogenetic analyses of the "bicornutum" group based on both ITS and D2D3 regions showed a clear separation of S. goweni n. sp. from the other species. In both analyses S. goweni n. sp. formed a strongly supported group of American species. PMID- 27395872 TI - A new Lepidoblepharis lizard (Squamata: Sphaerodactylidae) from the Colombian Guyana shield. AB - Lepidoblepharis lizards are tiny geckos of the forest leaf litter. This genus is distributed from Nicaragua to the Amazonian region of Peru and Brazil, and the genus currently contains 21 species. We found a new small Lepidoblepharis from eastern Colombia that we here describe as a new species. It is characterized by having granular or subconical dorsal scales; 10-13 subdigital lamellae under 4th toe; postmental border slightly or strongly projecting backwards, followed by 2-5 (usually 3) postmentals; and 20-31 scales across snout at lst/2nd supralabial suture. This new taxon is compared to all congeners. PMID- 27395873 TI - Peckia veropeso sp. nov., a flesh fly (Diptera: Sarcophagidae) from the Brazilian Amazon associated with riparian habitats. AB - A new species of Sarcophagidae, Peckia (Peckia) veropeso sp. nov., is described based on adult male specimens collected on organic residues in an urban open air market located on the riverside in Belem, Para state, Brazil, and in a nearby inundated forest. This species seems to be restricted to periodically inundated riparian habitats locally known as "varzea". The distiphallus of this species is similar to that of members of the monophyletic hilifera (Aldrich)-group in the subgenus Peckia Robineau-Desvoidy. It is distinguished from the other species in the subgenus by characteristics of the male terminalia, mainly in the shape of cercus and vesica. A modified key to species of the subgenus Peckia is included. PMID- 27395874 TI - A new species of Pseudochalcura Ashmead (Chalcidoidea: Eucharitidae) from Argentina with descriptions of alternate sexes of two other species. AB - Pseudochalcura Ashmead is a genus of parasitic wasps within Eucharitidae (Chalcidoidea) that are all parasitoids of ants. The genus is widespread in the New World, with different species known from the Yukon and Alaska to northern Chile and Argentina. Descriptions of the adults (both sexes) of Pseudochalcura carinata sp. nov. from Argentina, and of the males of P. pauca Heraty and P. prolata Heraty are provided. A revised identification key to species is included. PMID- 27395875 TI - Description of the 5th instar nymph of Oenopiella punctaria (Stal, 1859) Hemiptera: Heteroptera: Pentatomidae), with new distributional records
from Southern Patagonia. AB - The 5th instar nymph of Oenopiella punctaria (Stal, 1859) is described and illustrated for the first time, together with new distributional records from Patagonia. The new records are from Santa Cruz Province (Argentina), and the Magallanes Region (Chile). The latter is the southernmost record for this species and also for the Carpocorini in South America. In light of the new data, the biogeography of Oenopiella is discussed, and it is concluded that an Andean origin may be possible. PMID- 27395876 TI - Leuconidae (Crustacea: Cumacea) from the collections of the Museum Victoria, Australia. AB - The collections of the Museum Victoria have yielded six new leuconid species in five genera from Australian waters: Austroleucon adiazetos n. sp., A. dolosolevis n. sp., Eudorellopsis mykteros n. sp., Kontiloleucon australiensis n. gen., n. sp., Leucon (Alytoleucon) dolichorhinos n. sp., Ommatoleucon megalopos n. sp. as well as the new genus Kontiloleucon. Leucon (Leucon) echinolophotos n. sp. is a new species from off Enderby Land, Antarctica. Keys to the Australian leuconid genera and species are included. PMID- 27395877 TI - Commented checklist of marine fishes from the Galicia Bank seamount (NW Spain). AB - A commented checklist containing 139 species of marine fishes recorded at the Galician Bank seamount is presented. The list is based on nine prospecting and research surveys carried out from 1980 to 2011 with different fishing gears. The ichthyofauna list is diversified in 2 superclasses, 3 classes, 20 orders, 62 families and 113 genera. The largest family is Macrouridae, with 9 species, followed by Moridae, Stomiidae and Sternoptychidae with 7 species each. The trachichthyd Hoplostethus mediterraneus and the morid Lepidion lepidion were the most abundant species. Biogeographically, the Atlantic group, with 113 species (81.3%) is the best represented, followed by the Lusitanian one with 17 species (12.2%). Data on species abundance, as number of individuals caught, size and depth are reported. Habitat, distribution and vulnerability status are commented. Moreover, biometric data and meristic counts are also reported for several species. The results obtained showing a high fish biodiversity and a sensible number of threatened species, strongly support the future declaration of the Galicia Bank as a Marine Protected Area. PMID- 27395879 TI - Redescription of the Indo-Pacific scorpionfish Scorpaenodes guamensis (Quoy & Gaimard 1824) (Scorpaenidae), a senior synonym of seven nominal species. AB - The Indo-Pacific scorpionfish, Scorpaenodes guamensis (Quoy & Gaimard 1824), is redescribed on the basis of 137 specimens, including types, from a wide geographic range in the Indo-Pacific. Seven nominal species, Scorpaena rubropunctata Cuvier in Cuvier & Valenciennes 1829, Sebastes minutus Cuvier in Cuvier & Valenciennes 1829, Scorpaena chilioprista Ruppell 1838, Scorpaena polylepis Bleeker 1851, Centropogon echinatus Macleay 1881, Scorpaena erinacea Garman 1903, and Scorpaenopsis quiescens Seale 1906, are regarded here as junior synonyms of S. guamensis. The type status of these nominal species is discussed, and lectotypes of Scorpaena guamensis, Scorpaena rubropunctata, Sebastes minutus, and Scorpaena polylepis are herein designated. Validity of Scorpaenopsis scaber (Ramsay & Ogilby 1886) is also discussed. PMID- 27395878 TI - On the taxonomy of the Brazilian flea beetle genus Miritius Bechyne & Bechyne (Coleoptera: Chrysomelidae: Galerucinae: Alticini: Monoplatina)
with description of two new species. AB - A taxonomic study was performed on the Brazilian genus Miritius Bechyne & Bechyne of Monoplatina, Alticini. Here Miritius and two of its species are redescribed and descriptions for another two new species were provided: Miritius abdominalis Morais & Linzmeier sp. nov. (Mato Grosso, Brazil) and Miritius claudius Morais & Linzmeier sp. nov. (Mato Grosso and Mato Grosso do Sul, Brazil). For the first time characters of the male and female genitalia, illustrations and a key to the Miritius species are presented. PMID- 27395880 TI - Antennal sensory organs of Scathophaga stercoraria (Linnaeus, 1758) (Diptera: Scathophagidae): ultramorphology and phylogenetic implications. AB - Scathophaga stercoraria (Linnaeus, 1758) is a well-established insect model species involved in numerous investigations on behavior, biology, phylogeny, genetics and evolution. The antennal sensilla of S. stercoraria are examined via scanning electron microscopy in order to emphasize their importance on taxonomy and phylogeny. On antennal scape and pedicel, both microtrichiae and several sharp-tipped mechanoreceptors are observed, while another two structures, setiferous plaques and pedicellar button, are also detected on antennal pedicel. One type of sensory pit and four types of antennal sensilla, including trichoid sensilla, basiconic sensilla, coeloconic sensilla and clavate sensilla, are observed on antennal funiculus. Similarity and disparity of setiferous plaques among different calyptrate groups are analyzed in terms of phylogeny. The phylogenetic results supported by morphology of setiferous plaques strongly accord with the cladistic relations based on known molecular tree, implying the potential taxonomic and phylogenetic implications of the plaques in Calyptratae. PMID- 27395881 TI - A new mite of the genus Alliphis Halbert, 1923 from Iran (Acari: Eviphididae), with a summary of the world fauna. AB - A new species of mite belonging to the genus Alliphis Halbert, 1923 is described from Iran. The description of Alliphis carinatus Masan & Babaeian, sp. nov., is based on females collected on an unidentified coprid beetle of the genus Copris Geoffroy, 1762. The new species is unusual in having a strongly sclerotised dorsal shield with longitudinally oriented ridges. Among the 37 species which are or have been included in the genus Alliphis, only 15 of them can be now reliably classified within the genus, excluding Alliphis siculus (Oudemans, 1905) and Alliphis transversus Halliday, 2010, which probably require the new genera. Alliphis halberti Ryke & Meyer, 1957, Alliphis serrochaetae Ramaraju & Mohanasundaram, 1996 and Alliphis trichiensis Ramaraju & Mohanasundaram, 1996, are newly transferred to Alloseius Masan & Halliday, 2009 (Eviphididae), Neopodocinum Oudemans, 1902 (Macrochelidae) and Copriphis Berlese, 1910 (Eviphididae), respectively. PMID- 27395882 TI - A hidden pygmy devil from the Philippines: Arulenus miae sp. nov.-a new species serendipitously discovered in an amateur Facebook post
(Tetrigidae: Discotettiginae). AB - Arulenus miae Skejo & Caballero sp. nov. is described from Buknidon and Davao, Mindanao, the Philippines. The species was serendipitously found in an amateur photo posted in Orthoptera Facebook group by Leif Gabrielsen. Holotype and paratype are deposited in Nederlands Centrum voor Biodiversiteit in Leiden, the Netherlands. Detailed comparison with Arulenus validispinus Stal, 1877 is given. A new diagnosis of the genus and A. validispinus is given. The paper is part of the revision of the subfamily Discotettiginae. This study provides a good example of how social networks can be used as a modern tool of discovering biodiversity if the regulations of the International Code of the Zoological Nomenclature are followed. A brief insight into habitat and ecology of this rainforest and mountainous species is presented. PMID- 27395883 TI - Description of a new species of Oplitis Berlese, 1884, and the first record of a phoretic uropodid mite (Acari: Oplitidae) on a Neotropical solitary wasp (Hymenoptera: Vespidae). AB - The association of an uropodid mite with a solitary eumenine wasp is reported for the first time. Five mite specimens were found on a specimen of the wasp Zethus pallidus Smith, 1857, collected in southeastern Brazil. The mites are described as a new species, Oplitis ticumbi Kontschan & Bernardi sp. nov. In addition some notes on the biology of these mite specimens associated with Z. pallidus are presented. PMID- 27395884 TI - Systematics and diversity of deep-water Cheilostomata (Bryozoa) from Galicia Bank (NE Atlantic). AB - Galicia Bank is a large seamount situated c. 200 km off NW Iberia with a minimum depth of 600 m. It was recently included in Natura 2000, an EU-wide network of nature protection areas. We here present the first taxonomic descriptions of cheilostome bryozoans from this bank. The specimens were collected through the Spanish project INDEMARES (during BANGAL 0811 cruise conducted in 2011) and during two previous campaigns, the French Seamount 1 in 1987 and the German Victor Hensen in 1997). Twenty-five species were found, including 12 that are new to science, while five species remain in open nomenclature. Three new cheilostome genera (Breoganipora, Galiciapora and Placidoporella) are described. A lectotype is designated for Setosella vulnerata (Busk), and Palmicellaria tenuis Calvet is transferred to the genus Porella [as Porella tenuis (Calvet) n. comb.]. Additionally, our study shows that 48-60% of the bryozoan species are endemic to Galicia Bank. The degree of endemism of the Cheilostomata is thus the highest among all orders present on this seamount. PMID- 27395885 TI - The first micropterous species of the southern European genus Kakothrips (Thysanoptera: Thripidae). AB - The European genus Kakothrips Williams includes seven species (ThripsWiki 2015) that are known to be flower-living mainly on Fabaceae plants. The genus is recorded across Europe from Morocco to England, and eastwards to Syria and Iran (zur Strassen 2003). Only K. pisivorus (Westwood) is known from northern Europe, and this is the senior synonym of the type species K. robustus (Uzel) (Collins 2010). Closely related to Frankliniella, the species share with the members of that genus the character states of ctenidia present on tergite VIII anterolateral to the spiracles, and a complete row of setae on both longitudinal veins of the fore wing. Also, the pronotal anteromarginal and anteroangular setae are half as long as the posteroangular setae. The character states of the genus Kakothrips include: ocellar setae pair III arising between posterior ocelli; fore tarsus with an apical tooth, laterally; pronotal posterior margin without a pair of small setae between the major posteromarginal setae. In some of the species the males bear a pair of stout tubercles laterally on tergite VIII, and sternites III VI or III-VII of males have a transverse pore plate. All the described species are known only from macropterae, and they are similar to each other in structure. A few distinguishing characters include colour of body, fore wings and antennal segments; the shape, length and position of the fore tarsal tooth; size of body, antennal segments, and major setae; and in males, shape of sternal pore plates, and length of setae on tergite IX. PMID- 27395886 TI - Ibonikawhite, new replacement name for Whitea Descamps, 1977 (Orthoptera: Thericleidae), not Whitea Hutton, 1904 (Coleoptera: Pselaphinae), and standardised English names for the included species. AB - Marius Descamps (1977) established the genus Whitea for four new species of forbhoppers (Orthoptera: Thericleidae) from the present-day Mpumalanga, KwaZulu Natal and Eastern Cape provinces of South Africa. The type species (by original designation) is W. fissicauda Descamps, 1977. Descamps's genus name is, however, preoccupied by Whitea Hutton, 1904, the name of a monotypic shortwing mould beetle genus (Coleoptera: Staphylinidae: Pselaphinae) from New Zealand. Whitea Hutton is itself a replacement name and was involved in another nomenclatural muddle, resolved by Brown (1964). The type species of the pselaphine genus (by monotypy) is Euplectus laevifrons Broun, 1893: 1425. PMID- 27395887 TI - Cephalocteinae Mulsant et Rey, 1866 (Hemiptera, Heteroptera), a subfamily of Cydnidae new for the Italian fauna: first record of Cephalocteus scarabaeoides (Fabricius, 1807) from Sardinia. AB - Cephalocteus scarabaeoides is recorded from the south-western coast of Sardinia, in sandy habitat (marine dunes near the beach), for the first time. The species and the subfamily are new for the Italian fauna. PMID- 27395888 TI - Erythrodiplax leticia: Description of the female and updated geographic distribution (Odonata: Libellulidae). AB - The female of Erythrodiplax leticia Machado is described and illustrated. The geographic distribution of the species is updated, and notes on its natural history are provided. PMID- 27395889 TI - Intraspecific variation of the octotaxic system in Protoribates paracapucinus (Acari, Oribatida, Haplozetidae), with systematic and taxonomic considerations. AB - The octotaxic system of notogaster in poronotic oribatid mites (Acari, Oribatida) usually is represented by two types, either porose areas or saccules. These dermal gland structures are observed as constant for each species (except sexual dimorphism; see below), therefore their type often is used as key character, and in consequence of this, it is used in taxonomy and systematics as diagnostic character for different taxa levels from species to family (Subias 2004, online version 2015; Weigmann 2006; Norton & Behan-Pelletier 2009; Bayartogtokh 2010). However, there are exceptions: for Drymobates silvicola Grandjean, 1930 (Drymobatidae) and Galumna (Atypicogalumna) corpuzrarosae Ermilov, Sandmann, Klarner, Widyastuti & Scheu, 2015 (Galumnidae), a composite octotaxic system is known, including side by side porose areas and saccules in every specimen (Grandjean 1930; Ermilov et al. 2015). Behan-Pelletier (2015) reports several cases of sexual dimorphism of the octotaxic system in Poronota, all with different appearance of porose areas. But for the licneremaeoid Glanderemaeus hammerae Balogh & Csiszar, 1963 (whose familial placement is unclear) a unique sexual dimorphism in octotaxic system is described-males with saccules, females with porose areas (see also Norton et al. 1997). PMID- 27395890 TI - First record of the Indo-Pacific areolate grouper Epinephelus areolatus (Forsskal, 1775) (Perciformes: Epinephelidae) in the Mediterranean Sea. AB - The number of alien species in the Mediterranean Sea is steadily increasing and it seems that the pace has been accelerating since the turn of the century (Galil et al. 2014). In 2015 alone five additional fish species have been reported, Epinephelus geoffroyi (Klunzinger, 1870) (Golani et al. 2015); Stolephorus indicus (van Hasselt, 1823) (Fricke et al. 2015); Sardinella gibbosa (Bleeker, 1849) (Stern et al. 2015); Mobula japanica (Muller & Henle, 1841) (Capape et al. 2015); and Cryptocentrus caeruleopunctatus (Ruppell, 1830) (Rothman & Goren 2015). Among the ca. 100 alien fish species reported from the Mediterranean to date (Galil & Goren 2014), five Indo-Pacific species belong to the genus Epinephelus Bloch, 1793: Epinephelus coioides (Hamilton, 1822), Epinephelus fasciatus (Forsskal, 1775), Epinephelus malabaricus (Bloch and Schneider, 1804) Epinephelus merra Bloch, 1793 (Golani et al. 2013a) and Epinephelus geoffroyi (Klunzinger, 1870) (Golani et al. 2015). Additional alien Epinephelus species reported from the Mediterranean are excluded for various reasons (Golani et al. 2013b). Here we report the finding of a sixth Indo-Pacific species of this genus along the Mediterranean coast of Israel. PMID- 27395891 TI - A new record of Holarctic genus Odontothrips (Thysanoptera, Thripidae) from India with a new species. AB - The Holarctic genus Odontothrips of Megalurothrips genus-group was established by Amyot & Serville in 1843 with type species Thrips phaleratus Haliday (Mound & Palmer 1981, Mirab-balou & Chen 2011). This genus is known by 32 species from the Palearctic and Nearctic regions (ThripsWiki 2015), and these species are flower living and mainly associated with flowers of family Fabaceae (Xie et al. 2010). The pest status of Odontothrips species is uncertain, but some species are reported to cause superficial damage to the flowers on which they feed. O. confusus Priesner is reported as a pest on lucerne in France and Czech Republic (Pitkin 1972), and also on legumes in Romania (Pustai et al. 2015). O. loti (Haliday) is reported as a major pest on Alfalfa in north China, where it feeds on tender leaves and causes leaf curling, whitening and withering (Kou et al. 2011). PMID- 27395892 TI - East or west: to which subspecies does the type specimen of the Galah, Eolophus roseicapilla (Vieillot, 1817) (Aves: Cacatuidae), belong? AB - The Galah (Eolophus roseicapilla) is a pink-and-grey cockatoo, widespread in and endemic to Australia, and now familiar as a cage bird world-wide. It has three currently recognised subspecies: roseicapilla Vieillot, 1817 in the Australian west, kuhli Mathews, 1912 in the far north, and albiceps Schodde, 1989 in the east (Schodde 1997; Higgins 1999; Dickinson & Remsen 2013; del Hoyo & Collar 2014; Engelhard et al. 2015). The northern subspecies, kuhli, is not involved in the issue of type identity of roseicapilla, and so is not considered further here. First to distinguish east and west subspecies was G.M. Mathews (1912). Without explanation then or later, Mathews arbitrarily applied the senior specific name, Cacatua roseicapilla Vieillot, 1817 and its two objective synonyms based on the same type-eos Kuhl, 1820 and rosea Vieillot, 1822-to the eastern subspecies, and introduced the new name assimilis for the then supposedly undescribed western form. Mathews' lead was followed unquestioningly until the late 1980s when Schodde (1989) and Rowley (1990: 3) concluded that the type of Vieillot's roseicapilla was of the western subspecies, collected by the Baudin expedition in the region of Shark Bay on the mid-western Australian coast. Rowley (l.c.), but not Schodde (l.c.) contrary to Rowley's reference, went further to claim that it had been taken by Francois Peron in 1803, presumably on the brief return visit of Baudin in Le Geographe to Shark Bay en route to France. This left the eastern subspecies un-named, which Schodde (l.c.) accordingly described as albiceps. PMID- 27395893 TI - Additional information for Leptoglossus impictus (Stal 1859) (Hemiptera: Heteroptera: Coreidae: Coreinae: Anisoscelini) from Patagonia, Argentina. AB - The Patagonian subregion belongs to the Andean region, and is comprised of two provinces: Central Patagonia and Subandean Patagonia. It extends from central Mendoza, widening through Neuquen, Rio Negro, Chubut, and Santa Cruz, to northern Tierra del Fuego, and reaches Chile (Morrone 2006). The knowledge of terrestrial Heteroptera in this region is poor and is limited to a few contributions (e.g. Berg 1979, Breddin 1898, Pennington 1920, Faundez & Carvajal 2011, Faundez 2015). PMID- 27395894 TI - Phytoseiidae (Acari: Mesostigmata) of Morocco: new records, descriptions of five new species, re-descriptions of two species, and key for identification. AB - The family Phytoseiidae includes more than 2,300 species distributed all over the world. However despite the huge numbers of faunistic surveys carried out for more than 60 years, the fauna of some countries and particular ecosystems remain little explored. This paper reports results of surveys carried out in various regions of Morocco (from Sahara to Atlantic and Mediteranean coasts) in 2002 and 2003. A total of 43 species was found. Among them 19 are new for the Moroccan fauna and five are new to science. This paper provides the descriptions of these five new species, Neoseiulus thymeleae, Transeius audeae, Typhlodromus (Typhlodromus) ballotae, T. (T.) leclanti, T. (T.) mazarii, and re-descriptions of two species (Typhlodromus (T.) setubali and Typhlodromus (Anthoseius) clairathiasae. A key to females of the 52 species now known from Morocco is given. PMID- 27395895 TI - A new species of bent-toed gecko, genus Cyrtodactylus Gray, 1827 (Reptilia: Squamata: Gekkonidae), from Jawa Timur Province, Java, Indonesia, with taxonomic remarks on C. fumosus (Muller, 1895). AB - A new species of the gekkonid lizard genus Cyrtodactylus Gray, 1827 is described from Klakah, Lumajang Regency, Jawa Timur Province, Java, Indonesia. Cyrtodactylus klakahensis sp. nov. can be distinguished from all other congeners by the presence of (1) a deep precloacal groove in males, (2) three rows of enlarged precloacofemoral scales, of which the third row bears 37-38 pores in males, (3) three or four rows of enlarged scales between the precloacofemoral scale rows and the cloaca, forming distinct chevrons, (4) raised and strongly keeled dorsal tubercles in 15-19 rows at midbody, (5) an indistinct lateral fold, (6) 17-20 subdigital lamellae under the 4th toe, and (7) subcaudal scales which are not transversely enlarged. Cyrtodactylus klakahensis sp. nov. is only the third bent-toed gecko species described from Java, indicating that the diversity of this genus on this island has been neglected in the past. Furthermore, we confirm that C. fumosus (Muller, 1895) is a species that possesses a precloacal groove in males and is most likely restricted to northern Sulawesi. That species is defined by a single female holotype (NMB-REPT 2662). Specimens in museum collections catalogued as C. fumosus from localities elsewhere are misidentified and likely represent undescribed species. PMID- 27395896 TI - A new species of Pollenia Robineau-Desvoidy, 1830 from Jordan (Diptera: Calliphoridae: Polleniinae). AB - A new species, Pollenia bartaki sp. nov., assigned to the Pollenia rudis species group in Pollenia Robineau-Desvoidy, 1830, is described on the basis of a single male specimen captured in Jordan. Its strongly curved surstylus is unique in the genus. The nominal species Pollenia aurata Seguy, 1934 and P. bazini Seguy, 1934 are formally transferred to the genus Xanthotryxus Aldrich, 1930, comb. nov. PMID- 27395897 TI - First report of the land planarian Diversibipalium multilineatum (Makino & Shirasawa, 1983) (Platyhelminthes, Tricladida, Continenticola) in Europe. AB - Introduction of alien species may significantly affect soil ecosystems, through predation or disruption of components of native ecosystems (Winsor et al. 2004; Alvarez-Presas et al. 2014; Justine et al. 2014). Land planarians have been reported as alien species in soils throughout the world and, among those, some species are considered to be successful invaders, e.g. Platydemus manokwari de Beauchamp, 1963, Arthurdendyus triangulatus (Dendy, 1894), Bipalium adventitium Hyman, 1943, Bipalium kewense Moseley, 1878 and Dolichoplana striata Moseley, 1877 (Winsor et al. 2004; Alvarez-Presas et al. 2014; Justine et al. 2014, 2015). Soil moisture status seems to be an important element for their successful invasion (Fraser & Boag 1998). In Europe at least 18 species of alien land planarians have been recorded since now and some of them are considered as invasive ones, e.g. P. manokwari (cf. Justine et al. 2014). Although the alien land planarian B. kewense has been reported to occur in many greenhouses in Italy (Bello et al. 1995), no data are available on its establishment and/or impact on natural environments. On 28th September 2014, 20 specimens (~1 individual/m2) of the land planarian Diversibipalium multilineatum (Makino & Shirasawa, 1983) (Fig. 1), native to Japan, were collected under pots, branches and plastic materials in a private garden located in the center of Bologna (Emilia Romagna, Central Italy), near the urban park Giardini Margherita (44 degrees 29' N, 11 degrees 21' E; WGS84). Thirty plant species (both indigenous and alien), mainly cultivated as bonsai (e.g. Lagerstroemia indica L., Juniperus procumbens (Siebold ex Endl.) Miquel), were present in this shady, wet garden (25 m2). Between March 2014 and June 2015, 70 more specimens of D. multilineatum were collected at the same site, mainly at dusk and dawn after rain. Reproduction by fission and regeneration processes were observed in several of those specimens, which were kept for some time in captivity. A specimen of D. multilineatum was also collected in a garden in Leguevin (Haute-Garonne, France), which will be described in a forthcoming paper by Justine et al. (in prep.) (see also Kawakatsu et al. 2014). Specimens without a genital pore were initially ascribed to D. multilineatum on the basis of their external appearance: the dorsal surface was brownish yellow and presented five longitudinal stripes at the head plate and the neck, showing the typical appearance of the species. The middorsal stripe was widened at its anterior end, on the head plate, and at the pharynx level. The ventral pattern of the animals at the pharyngeal region was also characteristic, with the middorsal stripe widened at this level. The Italian Diversibipalium specimens used for the molecular analysis were fixed and preserved in absolute ethanol. Fragments of the mitochondrial gene COI and 28S ribosomal RNA nuclear gene (GenBank Acc. Numbers KU245358 and KU245357, respectively) were obtained using the procedure and COI primers described in Alvarez-Presas et al. (2008) and Sola et al. (2013). The French specimen's COI (Specimen MNHN JL177, GenBank Acc. Number KT922162) was obtained as described in Justine et al. (2015). 28S sequences of 14 Bipaliinae specimens and four Microplana species (outgroup) retrieved from GenBank were included in the phylogenetic analyses (Fig. 2). Sequence alignment was obtained by using the online software MAFFT version 7 (Katoh & Standley 2013), while ambiguously aligned positions were removed using the program Gblocks (Talavera & Castresana 2007) with default settings, excepting the minimum number of sequences for a flank position at the minimum value (set at 10) and with half of the allowed gap positions. The final alignment had a length of 1589 bp. We used two phylogenetic inference approaches: maximum likelihood (ML), using the RaxML 8.2.3 software (Stamatakis 2014), and Bayesian inferences (BI), using MrBayes 3.2.4 (Ronquist et al. 2012). The evolutionary model used, GTR+I+G, was estimated to be the best with the software jModeltest 2.1.7 (Darriba et al. 2012; Guindon & Gascuel 2003), using the Akaike Information Criterion (AIC). MrBayes analyses were performed for 10-milion generation with sampling parameters every 103 and a 25% default burn-in value for the final trees. Convergence of the two runs (average standard deviation of split frequencies << 0.01) and likelihood stationarity were checked. The maximum likelihood analyses were performed under 1000 bootstrap pseudoreplicates. The phylogenetic results show a close and highly supported relationship of the Italian Diversibipalium specimens with those from Japan and South Korea that have been identified as D. multilineatum (Fig. 2). Diversibipalium multilineatum is the sister-group of B. nobile Kawakatsu & Makino, 1982, but with low support. The COI sequences of the French (MNHN JL177) and the Italian Diversibipalium specimens were compared in Geneious v. 8.0.5 (http://www.geneious.com, Kearse et al. 2012) and were found to be identical. These results indicate that the species introduced in both countries is the same, and most probably concerns the species D. multilineatum. The pathways of introduction of D. multilineatum are currently unknown, although a relationship between the horticultural trade and the introduction of alien land planarians is well known (Alvarez-Presas et al. 2014 and references therein). Here we report the first occurrence of individuals of D. multilineatum outside Asia. The GenBank sequence of D. multilineatum from South Korea is not yet supported by a published description of the specimen, while it is debatable whether South Korea should be considered part of the natural range of D. multilineatum, which only seems to include Japan. In the present paper, we consider the South Korean animal to be an introduced specimen. Soil moisture status, temperature, and food availability are considered to be the main factors determining the presence of terrestrial planarians (Boag et al. 1998); the microclimatic conditions of the Italian garden were similar to plant nurseries and greenhouses, while an abundance of food was available, such as isopods [Porcellionides pruinosus (Brandt, 1833)], oligochaetes [Dendrobaena attemsi (Michaelsen, 1902) and several juveniles of Lumbricus spp.] and gastropods [Cernuella cisalpina (Rossmassler, 1837), Cornu aspersum (O.F. Muller 1774), Deroceras reticulatum (O.F. Muller, 1774), Discus rotundatus (O.F. Muller, 1774), Limacus flavus (Linnaeus, 1758), Milax nigricans (Philippi, 1836), Papillifera papillaris (Linnaeus, 1758), Pomatias elegans (O.F. Muller, 1774)]. Moreover, winter 2014 reached the highest temperatures and rainfall of the last two decades (source: CNR-ISAC, Bologna), thus favouring establishment and spread of D. multilineatum. The potential environmental impacts of some invasive flatworms are well documented (Alvarez-Presas et al. 2014; Justine et al. 2014) and, even if these effects have not yet been assessed for D. multilineatum, the adoption of precautionary measures and of early intervention is here strongly recommended (Genovesi & Shine 2004). Finally, knowledge of the introduction pathway(s), together with the analysis of prey preference and possible impact on the invertebrate fauna, will be essential to halt or at least to limit the spread of this introduced land flatworm. PMID- 27395898 TI - A new species of Megaselia Rondani (Diptera, Phoridae) with wing-spots from China. AB - The genus Megaselia was established by Rondani in 1856 with the type species Megaselia crassineura Rondani (=Phora costalis Roser, 1840) (Borgmeier 1968). About 1600 species are recorded and distributed all over the world (Fang & Liu 2015). In the genus Megaselia, species with wing-spots are rare. Only six species are recorded with wing-spots worldwide: M. conglomerata (Malloch) from North America (Borgmeier 1964), M. dickoni Wakeford & Disney and M. shadeae Hartop & Brown from Central America (Wakeford & Disney 1994, Hartop & Brown 2014), M. maculifera Beyer from Africa (Beyer 1965), M. chorogi Naumov from Georgia (Naumov 1979), and M. trimacula Fang & Liu from China (Fang & Liu 2015). PMID- 27395899 TI - Out of Africa: The first introduced African geophilomorph centipede record from a European greenhouse (Chilopoda: Geophilidae). AB - In Europe, 184 species of Geophilomorpha are recognised (Bonato & Minelli 2014) of which eight are evaluated as alien to the region (Stoev et al. 2010, Decker et al. 2014). Four of these have been reported from greenhouses exclusively: Mecistocephalus guildingii Newport, 1843, Mecistocephalus maxillaris (Gervais, 1837), Tygarrup javanicus Attems, 1929 and Pectiniunguis pauperatus Silvestri, 1907. In this paper, we report another species, Polygonarea silvicola Lawrence, 1955, which is the first Geophilomorpha species of unambiguous African origin in Europe. Description of the specimen found in Olomouc (Czech Republic) is provided. Co-occurrence of another African species, the lithobiomorph Lamyctes africanus (Porath, 1871) (also new for Czech Republic) is also reported here. PMID- 27395900 TI - The orb-weaving spider genus Chrysometa in Uruguay: distribution and description of a new species (Araneae, Tetragnathidae). AB - The spider genus Chrysometa Simon, 1895 comprises 138 species of small (3-5 mm) Neotropical orb-weavers spiders (Nogueira et al. 2011; World Spider Catalogue 2015) mainly associated with arboreal vegetation from intermediate to low altitude forests (Levi 1986). Males of Chrysometa differ from other tetragnathids by having the palpal tibial length approximately as long as its widest point; paracymbium articulated and with several apophyses located at both ends; male cephalic region narrower than in the female and having cymbial ectobasal and ectomedian processes. Females are diagnosed by having femora without trichobothria; abdomen covered with silver guanine patches; a flat epigynum and also by their fertilization ducts originating anteriorly and crossing over the spermathecae (Levi 1986; Alvarez-Padilla & Hormiga 2011). PMID- 27395901 TI - Description of the final stadium larva of Macromia calliope Ris, 1916
(Odonata: Anisoptera: Macromiidae). AB - The final stadium larva of Macromia calliope Ris is described and illustrated for the first time and diagnosed against other larvae of Chinese Macromia species on the basis of published descriptions. Among the fourteen known Chinese Macromia larvae, that of M. calliope can be separated from those of non-calliope-group species by having distinctive diamond-shaped black spots located at the outside of the base of the wing sheaths. And in five Chinese calliope-group species, the larva of M. calliope can be separated from that of M. flavocolorata by apical border of prementum not obviously projecting forwards; from that of M. septima by dorsal hook on S3 thinnest and tallest of all; from that of M. chui by a relatively smaller body; from that of M. urania by nine premental setae on each side of interior prementum, five longer ones accompanied medially by four shorter ones; and finally, from those of all other Chinese Macromia species by several distinctive large V-shaped black markings on mid-dorsum of distal abdominal segments. PMID- 27395902 TI - A replacement name for Asthenes wyatti perijanus Phelps 1977. AB - A recent near-complete phylogeny of the avian family Furnariidae (Derryberry et al. 2011) found a number of discrepancies between the phylogeny and the then current taxonomy of the group, and several changes were proposed to reconcile the taxonomy of the family with the phylogeny. Among these was the merging of the genus Schizoeaca Cabanis 1873 into Asthenes Reichenbach 1853 (Derryberry et al. 2010). This change has now been generally adopted. The Committee on Classification and Nomenclature (South America) of the American Ornithologists' Union (Remsen et al. 2015) passed a proposal to merge the genera in 2010, and recent global reference works (e.g., Dickinson & Christidis 2014) have likewise adopted the lumping of these genera. PMID- 27395903 TI - Erratum: NEVEEN S. GADALLAH, HASSAN GHAHARI & FRANCISCO JAVIER PERIS-FELIPO (2015) Catalogue of the Iranian Microgastrinae (Hymenoptera: Braconidae). Zootaxa, 4043(1): 001-069. PMID- 27395904 TI - Givetian ostracods of the Candas Formation (Asturias, North-western Spain): taxonomy, stratigraphy, palaeoecology, relationship to global events and palaeogeographical implications. AB - Asturian ostracods of the Givetian carbonate Candas Formation are documented for the first time from the Peran-Perlora and Carranques reference sections. More than 1,200 specimens were extracted from 44 samples by means of the hot acetolysis method. In all, 75 taxa are described herein, of which 21 are formally described and one, Evlanella peranensis Maillet n. sp., is new. All the taxa are marine benthic and belong to the Eifelian Mega-Assemblage. The assemblages recognized are representative of semi-restricted to shallow open-marine palaeoenvironments above the storm wave base. The stratigraphical distribution of the taxa shows a strong faunal renewal in the top of the Candas Formation. Long ranging taxa found at the base of the formation, of which many are known from the base of the Middle Devonian, disappear within the base of the member C and are replaced above, around the Middle/Upper Givetian boundary, by more cosmopolitan taxa characteristic of the Frasnian. The lower half of the member C is also characterized both by unstable environments and occurrence of some short-ranging opportunistic ostracod taxa. This renewal within shallow water ostracod communities is probably a consequence of the global Taghanic Biocrisis, leading world-widely to extinctions in several faunal groups. Faunal affinities with Givetian ostracod taxa reported in other areas of the world reflect the commonly accepted palaeogeographical patterns. Close relations between the Cantabrian Zone (NW-Spain), the Armorican Massif (W-France), the Mouthoumet Massif (S-France) and North Africa (Morocco and Algeria) suggest a narrow oceanic space between the western European terranes and the northern Gondwanan margin that involves an advanced phase of closure of the Medio-European Ocean. PMID- 27395905 TI - Revision and phylogenetic analysis of the orb-weaving spider genus Glenognatha Simon, 1887 (Araneae, Tetragnathidae). AB - A taxonomic revision and phylogenetic analysis of the spider genus Glenognatha Simon, 1887 is presented. This analysis is based on a data set including 24 Glenognatha species plus eight outgroups representing three related tetragnathine genera and one metaine as the root. These taxa were scored for 78 morphological characters. Parsimony was used as the optimality criterion and a sensitivity analysis was performed using different character weighting concavities. Seven unambiguous synapomorphies support the monophyly of Glenognatha. Some internal clades within the genus are well-supported and its relationships are discussed. Glenognatha as recovered includes 27 species, four of them only known from males. A species identification key and distribution maps are provided for all. New morphological data are also presented for thirteen previously described species. Glenognatha has a broad distribution occupying the Neartic, Afrotropic, Indo Malaya, Oceania and Paleartic regions, but is more diverse in the Neotropics. The following eleven new species are described: G. vivianae n. sp., G. caaguara n. sp., G. boraceia n. sp. and G. timbira n. sp. from southeast Brazil, G. caparu n. sp., G. januari n. sp. and G. camisea n. sp. from the Amazonian region, G. mendezi n. sp., G. florezi n. sp. and G. patriceae n. sp. from northern Andes and G. gouldi n. sp. from Southern United States and central Mexico. Females of G. minuta Banks, 1898, G. gaujoni Simon, 1895 and G. gloriae (Petrunkevitch, 1930) and males of G. globosa (Petrunkevitch, 1925) and G. hirsutissima (Berland, 1935) are described for the first time. Three new combinations are proposed in congruence with the phylogenetic results: G. argyrostilba (O. P.-Cambridge, 1876) n. comb., G. dentata (Zhu & Wen, 1978) n. comb. and G. tangi (Zhu, Song & Zhang, 2003) n. comb., all previously included in Dyschiriognatha Simon, 1893. The following taxa are newly synonymized: Dyschiriognatha montana Simon, 1897, Glenognatha mira Bryant, 1945 and Glenognatha maelfaiti Baert, 1987 with Glenognatha argyrostilba (Pickard-Cambridge, 1876) and Glenognatha centralis Chamberlin, 1925 with Glenognatha minuta Banks, 1898. PMID- 27395906 TI - A taxonomic revision of the genus Baldorhynchus (Di Marco & Osella, 2002) stat. n. (Coleoptera, Curculionidae, Entiminae). AB - The Otiorhynchus subgenus Baldorhynchus Di Marco & Osella, 2002 is revised and elevated to the genus level, stat. n.. The following species-level taxa were also elevated to the species level: Baldorhynchus caoduroi (Osella, 1983) stat. n. from Otiorhynchus (Baldorhynchus) amicalis caoduroi (Osella, 1983); Baldorhynchus comottii (Osella, 1983) stat. n. from Otiorhynchus (Baldorhynchus) moczarskii comottii (Osella, 1983); Baldorhynchus lessinicus (Osella, 1983) stat. n. from Otiorhynchus (Baldorhynchus) amicalis cenomanus (Colonnelli & Magnano, 2003) = Troglorhynchus amicalis ssp. lessinicus (Osella, 1983); Baldorhynchus toscolanus (Osella, 1983) stat. n. from Otiorhynchus (Baldorhynchus) kahleni toscolanus (Osella, 1983) and Baldorhynchus valvestinus (Osella, 1983) stat. n. from Otiorhynchus (Baldorhynchus) kahleni valvestinus (Osella, 1983). The following new combinations and resurrections are also proposed: Baldorhynchus carinatus (Osella, 1983) nom. res. from Troglorhynchus carinatus Osella (1983) = Otiorhynchus (Troglorhynchus) serradae Colonnelli & Magnano (2003); Otiorhynchus (Troglorhynchus) radjai (Di Marco & Osella, 2002) comb. n. from Otiorhynchus (Baldorhynchus) radjai Di Marco & Osella (2002); Baldorhynchus ferrarii (F.Solari, 1955) nom. res. from Troglorhynchus ferrarii F. Solari (1955) = Otiorhynchus (Baldorhynchus) adrianoi Magnano (2001); Baldorhynchus judicariensis (Osella, 1983) nom. res. from Troglorhynchus judicariensis Osella (1983) = Otiorhynchus (Baldorhynchus) clibbianus Colonnelli & Magnano (2003); Baldorhynchus lessinicus (Osella, 1983) nom. res. from Troglorhynchus amicalis ssp. lessinicus Osella (1983) = Otiorhynchus (Baldorhynchus) amicalis cenomanus (Colonnelli & Magnano, 2003). Twenty-one species are new to science: Baldorhynchus agostianus Bello & Osella sp. n., Baldorhynchus anachoreta Bello & Osella sp. n., Baldorhynchus bodeianus Bello & Osella sp. n., Baldorhynchus branchianus Bello & Osella sp. n., Baldorhynchus cohabitator Bello & Osella sp. n., Baldorhynchus danzii Bello & Osella sp. n., Baldorhynchus deceptor Bello & Osella sp. n., Baldorhynchus grottoloi Bello & Osella sp. n., Baldorhynchus magasaensis Bello & Osella sp. n., Baldorhynchus marianus Bello & Osella sp. n., Baldorhynchus metallarius Bello & Osella sp. n., Baldorhynchus monguzzii Bello & Osella sp. n., Baldorhynchus nardii Bello & Osella sp. n., Baldorhynchus paladinii Bello & Osella sp. n., Baldorhynchus pedersolii Bello & Osella sp. n., Baldorhynchus pivai Bello & Osella sp. n., Baldorhynchus regalini Bello & Osella sp. n., Baldorhynchus ruzzieri Bello & Osella sp. n., Baldorhynchus saccoi Bello & Osella sp. n., Baldorhynchus settei Bello & Osella sp. n. and Baldorhynchus tedeschii Bello & Osella sp. n.. Thirty-seven species are assigned to the genus Baldorhynchus. Finally, in addition to having redescribed Baldorhynchus moczarskii (Breit, 1913), we designate a neotype for Baldorhynchus baldensis (Czwalina, 1875). A key to species and groups of species, a checklist of all species, diagnosis, distribution maps and details of ecology are provided. PMID- 27395907 TI - Bryozoa of Floridan Oculina reefs. AB - The deep-water Oculina coral reefs on the continental shelf off the east central coast of Florida are a unique protected marine habitat. A complete inventory of the Oculina-associated fauna is important to support its conservation. This paper provides an inventory of the bryozoans of the Oculina reef area. Unusually, the bryozoan fauna is dominated by encrusting cribrilinid bryozoans. These include two new species of Puellina and three other Floridan-Atlantic shelf Puellina only recently described. Additional cribrilinid species belong to the genera Klugerella and Rosulapelta. Other bryozoans found in the habitat include 38 encrusting cheilostome species, six of them new to science, belonging to the genera Callopora, Parasmittina, Parasmittina, Smittina, Microporella and Stephanollona. Cyclostomes were only sparsely represented, comprising three encrusting taxa. PMID- 27395908 TI - An annotated catalogue of the Iranian Euphorinae, Gnamptodontinae, Helconinae, Hormiinae and Rhysipolinae (Hymenoptera: Braconidae). AB - The Iranian species diversity of five braconid subfamilies, Euphorinae (54 species in 16 genera and 8 tribes), Gnamptodontinae (4 species in 1 genus and 1 tribe), Helconinae (9 species in 5 genera and 2 tribes), Hormiinae (8 species in 4 genera and 2 tribe) and Rhysipolinae (3 species in 2 genera) are summarized in this catalogue. A faunistic list is given comprising both local and global distribution of each species under study as well as host records. In the present study ten new records are added to the Iranian fauna: Centistes (Ancylocentrus) ater (Nees), Centistes cuspidatus (Haliday), Meteorus affinis (Wesmael), Meteorus rufus (DeGeer), Microctonus brevicollis (Haliday), Microctonus falciger Ruthe, Peristenus nitidus (Curtis) (Euphorinae), Aspicolpus carinator (Nees), Diospilus capito (Nees) and Diospilus productus Marshall (Helconinae s.l.). Euphorus pseudomitis Hedwig, 1957 is transferred to the subfamily Hormiinae and Hormisca pseudomitis (Hedwig, 1957) is a new combination. PMID- 27395909 TI - Identification and reassessment of the specific status of some tropical freshwater midges (Diptera: Chironomidae) using DNA barcode data. AB - Chironomidae are a highly diverse group of insects. Members of this family are often included in programs monitoring the health of freshwater ecosystems. However, a difficulty in morphological identification, particularly of larval stages is the major obstacle to this application. In this study, we tested the efficiency of mitochondrial cytochrome c oxidase I (COI) sequences as the DNA barcoding region for species identification of Chironomidae in Thailand. The results revealed 14 species with a high success rate (>90%) for the correct species identification, which suggests the potential usefulness of the technique. However, some morphological species possess high (>3%) intraspecific genetic divergence that suggests these species could be species complexes and need further morphological or cytological examination. Sequence-based species delimitation analyses indicated that most specimens identified as Chironomus kiiensis, Tokunaga 1936, in Japan are conspecific with C. striatipennis, Kieffer 1912, although a small number form a separate cluster. A review of the descriptions of Kiefferulus tainanus (Kieffer 1912) and its junior synonym, K. biroi (Kieffer 1918), following our results, suggests that this synonymy is probably not correct and that K. tainanus occurs in Japan, China and Singapore, while K. biroi occurs in India and Thailand. Our results therefore revealed the usefulness of DNA barcoding for correct species identification of Chironomidae, particularly the immature stages. In addition, DNA barcodes could also uncover hidden diversity that can guide further taxonomic study, and offer a more efficient way to identify species than morphological analysis where large numbers of specimens are involved, provided the identifications of DNA barcodes in the databases are correct. Our studies indicate that this is not the case, and we identify cases of misidentifications for C. flaviplumus, Tokunaga 1940 and K. tainanus. PMID- 27395910 TI - Systematic revision of Calligrapha Chevrolat (Coleoptera: Chrysomelidae)
with pale spots on dark elytra and description of two new species. AB - In this work, a group of seven species of Calligrapha (Coleoptera: Chrysomelidae) with pale spots contrasting with dark background of elytra is revised and their distributions specified based on the material studied from sixteen museums. Among these species, two are new and formally described: C. pavimentata sp. nov. and C. zapoteca sp. nov. A pragmatic identification key is provided to identify these taxa and it is proposed that these species belong to four different evolutionary lineages. PMID- 27395911 TI - Epidorylaimus monhystera sp. n., an atypical species of the genus Epidorylaimus Andrassy, 1986 (Dorylaimida: Qudsianematidae) from Japan. AB - Epidorylaimus monhystera sp. n. is described and illustrated from Japan. The new species is characterized by having 1.12-1.33 mm long body, lip region offset by slight constriction, odontostyle 15-16 MUm and odontophore 18-20 MUm long, guiding ring single, pharyngeal expansion gradual, vulva transvers, female genital system mono-opisthodelphic, anterior branch completely absent and tail elongated-conoid, ventrally arcuate. It is distinctive from all other species of the genus Epidorylaimus in having mono-opisthodelphic female genital system. Its relationship with other monodelphic genera of Qudsianematidae is also discussed and an emended diagnosis of the genus Epidorylaimus is provided with list of valid species, key for their identification and a diagnostic compendium. PMID- 27395912 TI - Review of species of the Astyanax bimaculatus "caudal peduncle spot"
subgroup sensu Garutti & Langeani (Characiformes, Characidae) from the rio La Plata and rio Sao Francisco drainages and coastal systems of southern Brazil and Uruguay. AB - The species of the Astyanax bimaculatus 'caudal peduncle spot' subgroup of the drainages of the rios La Plata and Sao Francisco, as well as southeastern coastal systems of Brazil and Uruguay, are revised. Two nominal species are considered valid and are redescribed: Astyanax lacustris and A. abramis. Astyanax jacuhiensis, A. asuncionensis and A. altiparanae are recognized as new junior synonyms of A. lacustris. Bertoniolus paraguayensisis recognized as a new junior synonym of A. abramis. The names Astyanax orbignyanus, A. vittatus, and A. borealis are considered species inquirendae. Notes on A. maculisquamis, included in the 'caudal peduncle spot' subgroup from rio Guapore (rio Madeira drainage), and Astyanax bahiensis from Bahia, mistakenly considered of the same subgroup, are presented. PMID- 27395913 TI - Mataranka bilyi, a new peculiar genus and species of Clavigeritae (Coleoptera: Staphylinidae: Pselaphinae) from Australia. AB - Mataranka bilyi, gen. and sp. nov. is described based on one male collected in the Northern Territory, Australia. The genus is placed into the subtribe Clavigerodina. The summary of all 14 genera of Clavigeritae with 6 antennomeres, Archiclaviger Heller, 1936; Claviger Preysler, 1790; Clavigeropsis Raffray, 1882; Corynotopsis Jeannel, 1951; Dejaegeria Jeannel, 1964; Gericlavodes Jeannel, 1960; Hexamerodes Jeannel, 1959; Mataranka gen. nov.; Mesoleptochir Jeannel, 1959; Palaeoclaviger Reichensperger, 1930; Tapas Besuchet, 2008; Xenalluaudia Raffray, 1913; Xenomussardia Celis, 1975 and Zuluclavodes Hlavac, 2007, with a short diagnosis is given. PMID- 27395914 TI - A new species of Onthophagus (Scarabaeoidea: Scarabaeinae) from the Mexican Transition Zone, with remarks on its relationships and distribution. AB - A new American Onthophagus of the chevrolati species-group is described (Onthophagus bolivari sp. nov.), providing also identification keys to the aztecus complex. Dorsal habitus and genital structures of the new species are illustrated. The relationships and geographical distribution of the aztecus complex are discussed, giving particular attention to the evolutionary history of O. bolivari. PMID- 27395915 TI - A new species of the genus Polyodaspis Duda, 1933 (Diptera: Acalyptratae: Chloropidae) from Central Asia with a key to the Palaearctic species. AB - A new species, Polyodaspis ferulae n. sp., from Central Asia (Uzbekistan) is described. The species was collected on inflorescences of Ferula foetida (Apiaceae). Siphonella levicola Becker in Becker and Stein, 1913 described from Iran is synonymized with Polyodaspis sulcicollis (Meigen, 1838) based on investigation of the holotype. A key to 9 species of the genus Polyodaspis Duda, 1933 is proposed with illustrations of male genitalia. Polyodaspis and Anacamptoneurum Becker, 1903 are treated as separate genera. New localities of P. sulcicollis (Meigen, 1838) from Kazakhstan and Central Asia are given. PMID- 27395916 TI - Zevinaella-a new barnacle genus (Scalpellomorpha: Arcoscalpellinae) associated with crinoids (Echinodermata) from the Caribbean. AB - A new genus, Zevinaella (Cirripedia: Scalpellomorpha: Scalpellidae: Arcoscalpellinae), is proposed to accommodate Trianguloscalpellum rodstromi (Boone, 1927) from Belize and Z. volentis gen. et sp. nov. from the Lesser Antilles, both occurring on crinoids. These two species are unique in lacking lower lateral plates (inframedian or second latera, L2s). We see no compelling evidence that the lack of L2s in Zevinaella is a consequence of fusion with the carinolatera (CLs), as appears to be the case in a near relative T. pentacrinarum, or of progressive reduction and potential loss, as in older specimens of Amigdoscalpellum spp. (Zevina, 1978b). However, this does not weaken the diagnosis of the new genus and, accordingly, the diagnoses for the family Scalpellidae Pilsbry, 1907 and the subfamily Arcoscalpellinae Zevina, 1978b are amended to accommodate the absence of the L2s. PMID- 27395917 TI - Validation of the synonymy of the teleost blenniid fish species Salarias phantasticus Boulenger 1897 and Salarias anomalus Regan 1905 with Ecsenius pulcher (Murray 1887) based on DNA barcoding and morphology. AB - As currently recognized, Ecsenius pulcher includes Salarias pulcher (type material has a banded color pattern), S. anomalus (non-banded), and S. phantasticus (banded). The color patterns are not sex linked, and no other morphological features apparently distinguish the three nominal species. The recent collection of banded and non-banded specimens of Ecsenius pulcher from Iran has provided the first tissue samples for genetic analyses. Here we review the taxonomic history of E. pulcher and its included synonyms and genetically analyze tissue samples of both color patterns. Salarias anomalus is retained as a synonym of E. pulcher because DNA barcode data suggest that they represent banded and non-banded color morphs of a single species. Furthermore, the large size of the largest type specimen of S. anomalus (herein designated as the lectotype) suggests that it belongs to E. pulcher. A single non-banded specimen from Iran is genetically distinct from E. pulcher and appears to represent an undescribed species. Salarias phantasticus is retained as a synonym of E. pulcher because the primary morphological difference between the two nominal species-presence of spots on the dorsal fin in E. pulcher and absence of those spots in S. phantasticus-is not a valid taxonomic character; rather, the spots represent galls that contain the larval stages of a parasitic crustacean. As males and females of Ecsenius species have been confused in the literature, we describe and illustrate the genital regions of both and comment on possible new blenniid synapomorphies that our investigation revealed. PMID- 27395918 TI - Description of two new species of Charinus Simon, 1892 from Brazilian caves with remarks on conservation (Arachnida: Amblypygi: Charinidae). AB - The genus Charinus comprises eleven described species in Brazil. Herein we describe two new species, Charinus caatingae sp n. and Charinus iuiu sp n., from caves of the state of Bahia, Brazil. Charinus caatingae is threatened, requiring special attention to its conservation. Furthermore, we present an updated identification key and a table of characters for the genus in the country. PMID- 27395919 TI - Redescriptions of Scirtidae (Coleoptera: Scirtoidea) described by Carl Henrik Boheman (1796-1868) with notes on Scirtes adustus iversenotatus Pic, 1930. AB - Boheman described four species of Scirtidae: one from Sweden (Cyphon pallidulus Boheman, 1850), two from South Africa (Elodes caffer Boheman, 1851 & Elodes marginipennis Boheman, 1851), and one from Argentina (Scirtes adustus Boheman, 1858). Cyphon pallidulus Boheman is a junior synonym of Contacyphon ochraceus (Stephens, 1830). Types of the remaining species were never re-examined, and none of them were redescribed. In the present paper, three species are redescribed on the basis of type specimens deposited in the Swedish Natural History Museum in Stockholm. Genitalia are illustrated for the first time and a new combination is proposed: Brachycyphon marginipennis (Boheman, 1851). The type specimen of a variety described by Pic, S. adustus var. diversenotatus, was examined and revealed to represent a distinct species, which is redescribed under the name of Scirtes diversenotatus Pic, 1930 stat. nov. in the present paper. PMID- 27395920 TI - Brachyopa minima (Diptera: Syrphidae), a new species from Greece with notes on the biodiversity and conservation of the genus Brachyopa Meigen in the Northern Aegean Islands. AB - An on-going study of the hoverfly fauna of the Northern Aegean Islands (Greece) has revealed the presence of four species of the genus Brachyopa Meigen. During the survey the following species were found: B. bicolor (Fallen), B. quadrimaculosa Thompson in Kaplan & Thompson, B. minima Vujic & Perez-Banon sp. nov. and an unidentified species very close to B. pilosa (Collin). Morphological characters and mitochondrial COI barcodes were used to link different life stages of B. minima, and to identify a larval specimen of B. bicolor. In this study adult and larval morphology and habitat preferences for B. minima are described. The description of larval morphology of B. bicolor and Brachyopa sp. aff. pilosa is amended too. An identification key to the adults of the B. quadrimaculosa group sensu Kassebeer (2002) in the Eastern Mediterranean (Greece, Israel and Turkey) is provided. The importance of specific microhabitats for the continued existence of these taxa is discussed. PMID- 27395921 TI - Review of the fur-mite genus Soricilichus Fain, 1970 (Acariformes: Chirodiscidae) symbionts of the African shrews of the subfamily Crocidurinae (Soricomorpha: Soricidae). AB - The fur-mite genus Soricilichus Fain, 1970 (3 species) (Acariformes: Chirodiscidae) represented by permanent symbionts of the African shrews of the subfamily Crocidurinae (Soricomorpha: Soricidae) is revised. The external morphology of these species was investigated with light and scanning electron microscopy. Based on the type specimens and newly obtained samples, 2 recognized species, S. scutisorex Fain, 1970 from Scutisorex somereni Thomas and S. kivuensis Fain, 1981 from Crocidura sp.-both are from DR of Congo-are redescribed. A new species S. sylvisorex sp. nov. found on shrews of the genera Sylvisorex (S. granti Thomas (type host), S. lunaris Thomas, S. vulcanorum Hutterer and Verheyen) and Crocidura (C. denti Dollman, C. cf. niobe, Crocidura sp.), collected in the DR Congo is also described. An amended generic diagnosis, including description of female immature stages, and a key to species are provided. PMID- 27395922 TI - [Not Available]. AB - In this study, a new "non-oxytrichid Dorsomarginalia" ciliate, Urosomoida sejongensis n. sp. discovered from freshwater of the King George Island, Antarctica, was investigated using morphological, morphometrical, and molecular methods. Morphology of U. sejongensis is characterized as follows: body shape slender to elongated; cortical granules spherical and colorless, groups of granules formed patchy distribution; ring-shaped structures scattered in cytoplasm; 27-30 adoral membranelles with undulating membranes in Oxytricha pattern; usually 17 frontal-ventral-transverse (FVT) cirri composed of 3 frontal, 1 buccal, 4 frontoventral, 3 postoral ventral, 2 pretransverse ventral and 4 transverse cirri; 1 right and 1 left marginal rows; 3 dorsal kineties with 1 dorsomarginal row, 3 caudal cirri; 1 micronucleus between 2 macronuclear nodules. This new species mainly differs from other congeners by the combination of following morphological features: a micronucleus, cortical granules, and ciliatures (e.g., adoral membranelles, FVT cirri). Urosomoida sejongensis shows a nucleotide similarity of 97.3% with U. agilis, type of this genus, using the SSU rDNA sequence. Molecular phylogeny shows a non-monophyletic relationship among Urosomoida species and emphasizes the need for further morphogenetic studies of this genus and other related species to resolve morphological convergences. PMID- 27395923 TI - A new species of spider belonging to the Pardosa lugubris-group (Araneae: Lycosidae) from Far East Asia. AB - A new species, Pardosa koponeni sp. n., is described. The new species is widely distributed in Far East Asia. It was previously confused with P. lugubris (Walckenaer, 1802). The two species have very similar copulatory organs but differ in the colouration of legs II-IV in males and the carapace/femur I ratio in both sexes. The distribution of the new species is mapped using material examined and literature data. To provide a more complete understanding of the boundaries between such closely related species, morphological and DNA barcoding approaches for species discrimination were integrated. Two species of the Pardosa lugubris-group (P. lugubris and P. alacris) were found to share haplotypes, suggesting evidence of hybridization or incomplete lineage sorting, or they are perhaps separate morphotypes of the same species. This is another example of complexity and the value of comparing morphology and DNA barcode data among spiders. PMID- 27395924 TI - Two new species of the Anemadus taiwanus species-group (Coleoptera: Leiodidae: Cholevinae: Anemadini) from China. AB - Anemadus perreaui sp. nov. and A. sichuanus sp. nov., both belong to the A. taiwanus species-group (Coleoptera: Leiodidae: Cholevinae, Anemadini), are described from Sichuan Province, China. Color plates and line drawings are offered to illustrate their important characteristics. A key to all species of the group is compiled so as to include the two new species. PMID- 27395925 TI - New species of Hexabdella and Neomolgus (Acari: Prostigmata: Bdellidae) from Iran. AB - A new species of Hexabdella Van der Schyff, Theron & Ueckermann (Acariformes: Bdellidae), H. quercusi Eghbalian, Khanjani, Safaralizadeh, Ueckermann sp. nov., and a new species of Neomolgus Oudemans, N. iraniensis Eghbalian, Khanjani, Safaralizadeh, Ueckermann sp. nov., are described and illustrated. A key is provided for adult females of all known species of Hexabdella, as well as for adult females of Neomolgus from Asian and neighbouring countries, including Iran, Japan and the Siberian region of Russia. All specimens were collected from soil and litter under oak trees, Quercus brantii Lindley (Fagaceae), or from soil and litter under wild almond, Amygdalus scoparia L. (Rosaceae), from western Iran. PMID- 27395926 TI - Leaf-rolling sawflies (Hymenoptera, Pamphiliidae, Pamphiliinae) of Tianmushan Mountains, Zhejiang Province, China. AB - Two species of Neurotoma, six species of Onycholyda, and five species of Pamphilius are recorded from Tianmushan, Zhejiang Province, China, and a key is given to these three genera and 13 species. Three new species, Onycholyda atra Shinohara & Wei, sp. nov. from Zhejiang Province, O. fulvicornis Shinohara, sp. nov. from Shaanxi Province and Zhejiang Province, and Pamphilius padus Shinohara, sp. nov. from Zhejiang Province, are described. New distribution records are: Onycholyda shaanxiana Shinohara, 1999, from Hubei Province, Zhejiang Province and Guangxi Zhuang Autonomous Region, O. subquadrata (Maa, 1944) from Zhejiang Province, O. tianmushana Shinohara & Xiao, 2006, from Hunan Province and Jiangxi Province, Pamphilius palliceps Shinohara & Xiao, 2006, from Anhui Province, P. lizejiani Shinohara in Shinohara & Wei, 2012, from Zhejiang Province, P. shengi Wei in Wei & Xiao, 1999, from Hubei Province and Zhejiang Province, and P. qinlingicus Wei in Wu & Wei, 2010, from Zhejiang Province. The larva of P. padus feeds on Padus obtusata (Rosaceae) and that of P. palliceps feeds on Rosa multiflora (Rosaceae), both singly making a leaf-roll. Rubus peltatus (Rosaceae) is recorded as a host plant of O. atra based on the observation of oviposition. PMID- 27395927 TI - Three new species of Papuagrion Ris, 1913 (Odonata: Coenagrionidae) from the Hindenburg Wall region of western Papua New Guinea. AB - Three distinctive new species of Papuagrion Ris, 1913 are described from a high altitude area (1,770-1,820 m a.s.l.) at the base of the Hindenburg Wall, Western Province, Papua New Guinea. These are P. chrysosoma sp. nov., P marijanmatoki sp. nov. and P. tydecksjuerging sp. nov.; all type material is deposited in the South Australian Museum (SAMA). These were the only species of the genus collected at higher altitudes in the Ok Tedi headwaters, and none of them were encountered at lower altitudes (300-900 m) despite intensive searches there. The new species described here bring to 26 the number of Papuagrion species known from the New Guinea region. PMID- 27395928 TI - Notes on Afrotropical Catharsius species described by Edgar von Harold (Coleoptera: Scarabaeidae, Scarabaeinae). AB - The type material of the Afrotropical Catharsius species described by E. von Harold is studied. Lectotypes are designated for C. camillus, C. dux, C. harpagus, and C. pandion. Habiti, aedeagi and original labels of the primary types are illustrated. Catharsius mossambicanus Ferreira, 1960 is here considered a junior synonym of C. pandion Harold, 1877. An alloreferent male is designated and illustrated for C. dux Harold, 1878 in order to illustrate males of this species in which females are undistinguishable from C. duciformis Ferreira, 1959. PMID- 27395929 TI - A revised phylogenetic classification of the ant subfamily Formicinae (Hymenoptera: Formicidae), with resurrection of the genera Colobopsis and Dinomyrmex. AB - The classification of the ant subfamily Formicinae is revised to reflect findings from a recent molecular phylogenetic study and complementary morphological investigations. The existing classification is maintained as far as possible, but some tribes and genera are redefined to ensure monophyly. Eleven tribes are recognized, all of which are strongly supported as monophyletic groups: Camponotini, Formicini, Gesomyrmecini, Gigantiopini, Lasiini (= Prenolepidii syn. n.), Melophorini (= Myrmecorhynchini syn. n.; = Notostigmatini syn. n.), Myrmelachistini stat. rev. (= Brachymyrmicini syn. n.), Myrmoteratini, Oecophyllini, Plagiolepidini, and Santschiellini stat. rev. Most of the tribes remain similar in content, but the generic composition of Lasiini, Melophorini, and Plagiolepidini is changed substantially. Species that have been placed in the genus Camponotus belong to three separate lineages. To ensure monophyly of this large, cosmopolitan genus we institute the following changes: Colobopsis and Dinomyrmex, both former subgenera of Camponotus, are elevated to genus level (stat. rev.), and two former genera, Forelophilus and Phasmomyrmex, are demoted to subgenus status (stat. n. and stat. rev., respectively) under Camponotus; two erstwhile subgenera of Phasmomyrmex, Myrmorhachis and Myrmacantha, become junior synonyms (syn. n.) of Camponotus (Phasmomyrmex); and the Camponotus subgenus Myrmogonia becomes a junior synonym (syn. n.) of Colobopsis. Dinomyrmex, represented by a single species from southeast Asia, D. gigas, is quite distinctive, but Camponotus and Colobopsis exhibit more subtle differences, despite being well separated phylogenetically. We identify morphological features of the worker caste that are broadly useful for distinguishing these two genera. Colobopsis species on the islands of New Caledonia and Fiji-regions with few native Camponotus species-tend to exceed these diagnostic bounds, but in this case regionally applicable character differences can be used to distinguish the two clades. Despite confusing similarities in the worker caste Colobopsis and Camponotus retain diagnostic differences in their larvae and pupae. PMID- 27395930 TI - Paraphelliactis tangi n. sp. and Phelliactis yapensis n. sp., two new deep-sea species of Hormathiidae (Cnidaria: Anthozoa: Actiniaria) from a seamount in the tropical Western Pacific. AB - Two new species of hormathiid actiniarians, Paraphelliactis tangi n. sp. and Phelliactis yapensis n. sp., are described from a seamount near the Yap Trench in the tropical Western Pacific. Paraphelliactis tangi n. sp. has a thick cuticle, a tuberculated column divisible into scapus and scapulus, a complete fifth cycle of mesenteries, an equal number of mesenteries at the margin and at the limbus, and up to 192 tentacles without aboral mesogloeal thickenings that are hexamerously arranged in six cycles. This species differs distinctly from the three known species of Paraphelliactis by the above mentioned features (vs. an incomplete fifth cycle of mesenteries, usually more mesenteries at the margin than at the limbus, and the tentacles with aboral mesogloeal thickenings). So far, it is the only member of the genus Paraphelliactis found in the Western Pacific. Phelliactis yapensis n. sp. has an asymmetric bilobed oral disc and column, tuberculated scapus and scapulus, an incomplete fifth cycle of mesenteries, and up to 162 tentacles with aboral mesogloeal thickenings that are alternately arranged in two cycles. In comparison with other Phelliactis species, the basitrichs of mesenterial filaments of Ph. yapensis are distinctly larger. Phelliactis yapensis n. sp. is the fourth species of Phelliactis found in the Western Pacific. PMID- 27395931 TI - Metapeachia schlenzae sp. nov. (Cnidaria: Actiniaria: Haloclavidae) a new burrowing sea anemone from Brazil, with a discussion of the genus Metapeachia. AB - The diversity of burrowing sea anemones from Brazil is poorly known with only three species recorded. Metapeachia schlenzae sp. nov. is described from specimens collected in the intertidal zone of Sao Sebastiao and Cabo Frio in the southeastern coast of Brazil. Metapeachia schlenzae sp. nov. is the second species described for the genus and the second haloclavid recorded from Brazil. A comparison between Metapeachia schlenzae sp. nov. and Metapeachia tropica, the type species of the genus, is included. The two valid species of Metapeachia differ in the morphology of the conchula, internal anatomy, cnidae and geographical distribution. PMID- 27395932 TI - A new species of the genus Anthaxia Eschscholtz, 1829 from Mauritania (Coleoptera: Buprestidae: Anthaxiini). AB - Although the Buprestid fauna of the Sahel is relatively well-known many new species have been discovered in this region in the course of the last decades. Also many new species of the tribe Anthaxiini, whose life cycle is connected with the plant genus Acacia (Fabaceae), have been described since the last (and first) comprehensive study by Mateu (1972). This exhaustive paper deals with all insects developing in (or living on) Acacia spp. During the project dealing with the pests of the genus Acacia in Mauritania and Benin run by J. F. Vayssieres (IITA), a new species of Anthaxia Eschscholtz, 1829 was discovered; the description of this new species is given in this paper. PMID- 27395933 TI - Macrothemis meurgeyi Daigle, 2007, from Guadeloupe is a junior synonym of Macrothemis celeno (Selys in Sagra, 1857) (Odonata; Libellulidae). AB - The genus Macrothemis consists of 40 Neotropical species (Garrison et al. 2006). Recently, a new species, Macrothemis meurgeyi from Guadeloupe (French West Indies), was described based on specimens from Habitation Deravin, Basse-Terre (Daigle 2007). PMID- 27395934 TI - A new species of Polyplectropus Ulmer 1905 (Trichoptera: Polycentropodidae) from Minas Gerais State, southeastern Brazil. AB - The adult male of a new species of the genus Polyplectropus Ulmer 1905a is described and illustrated based on specimens collected in Parque Nacional da Serra da Canastra, southeastern Brazil. Polyplectropus canastra sp. nov. can be distinguished from other Polyplectropus species by the shape of sternum IX, by the thumb-like mesolateral process of each preanal appendage, by the rectangular ventral branch of each inferior appendage in ventral view, and by the curved claw like spines of the endothecal membrane. Among all species in the P. annulicornis Group, P. canastra is the only one with a bifid dorsolateral process of each preanal appendage and bearing spinules on the distal half of the rod-like lateral branch. PMID- 27395935 TI - What is Lethe hyrania (Kollar, 1844) (Lepidoptera, Nymphalidae, Satyrinae)? AB - Known for a long time as "Lethe insana [sic] (Kollar, 1844)" (e.g. Fruhstorfer, 1911; D'Abrera, 1985), Lethe hyrania (Kollar, 1844) is a common, sexually dimorphic, satyrine butterfly, found in the Sino-Himalayan region. Kollar (1844) described simultaneously both Satyrus isana and S. hyrania, as separate but closely related species, from northwestern India. Kollar (1844) spelt the name of the former in two different ways, as isana in the text (pp. 448, 449, 585), and as jsana in the legend for plate 16. Westwood (1851) maintained isana and hyrania as separate species but transferred them to the genus Debis Doubleday, whereas both Butler (1868) and Kirby (1871) assigned them to the genus Lethe Hubner, synonymizing isana under L. rohria (Fabricius). Moore (1882) was the first author to regard isana and hyrania as conspecific, the former representing the female sex and the latter the male, though he misspelt isana as "isania". Acting as First Reviser, Article 24.2 of ICZN (1999), Moore (1882) gave precedence to hyrania, thus the valid name for the species is Lethe hyrania. Later, Marshall & Niceville (1883), Niceville (1886), Doherty (1886), Elwes (1888), and Moore (1892) followed Moore's (1882) opinion, though afterwards Mackinnon & Niceville (1897) argued that isana had priority over hyrania, based on "page precedence", ignoring Moore's (1882) previous action. Bingham (1905) was the first author to introduce the incorrect subsequent spelling "insana" and, apparently following Mackinnon & Niceville (1897), also gave precedence to "insana" over hyrania. Most subsequent authors followed Bingham's (1905) error, and used Lethe "insana" for this species (for instance, Fruhstorfer, 1911; Evans, 1923, 1927; Gaede, 1931; Talbot, [1949]; Lesse, 1957; D'Abrera, 1985, 1990; Bozano, 1999). Except for Bozano (1999), who listed both hyrania and "insana" as valid species, without further comment, the name hyrania has been forgotten for over a hundred years. PMID- 27395936 TI - The Amphipoda of Sea City, Kuwait.-The Senticaudata (Crustacea). AB - Thirteen species of Amphipoda Senticaudata were collected in Sea City, Kuwait using a Van Veen grab and an Ocklemann sledge. Of these seven species were new to science and are described and figured in this contribution. PMID- 27395937 TI - Three new species of Calliceratomyia Lane (Diptera: Ditomyiidae) from Neotropical Mexico. AB - Three new species of the ditomyiid genus Calliceratomyia Lane, so far known only from the type-species from southeastern Brazil, are described from Mexico. The new species-Calliceratomyia papaveroi sp. n., Calliceratomyia pantelhomyia sp. n. and Calliceratomyia zayolli sp. n.-are described based on adult males collected with Malaise traps in the States of Oaxaca, Chiapas and Hidalgo, Mexico. The descriptions are illustrated and the diagnosis of the genus is revised. PMID- 27395938 TI - Notes on the Rhyacophila scissa species group with description of two new taxa from China (Trichoptera, Rhyacophilidae). AB - One new species, R. meniscoides n. sp., and 1 new subspecies, R. morsei concaviuscula n. sp., are described, diagnosed and illustrated. Two diagnostic species complexes within the R. scissa Species Group, the R. scissa Diagnostic Species Complex and the R. schismatica Diagnostic Species Complex, are recognized and delimited. The 15 previously described species and 1 new species and 1 new subspecies described in this article are assigned to the complexes accordingly. Distribution maps of all 17 members in the Species Group are presented. PMID- 27395939 TI - Clavigeroscydmus Franz, a new junior synonym of Scydmaenus Latreille (Coleoptera, Staphylinidae, Scydmaeninae). AB - The monospecific genus Clavigeroscydmus Franz, based on a single teneral female collected in Madagascar, was one of the most enigmatic taxa within Scydmaenini. Recent rediscovery of Clavigeroscydmus corticariaeformis Franz, including previously unknown males, made it possible to study morphological structures of this species and to verify its taxonomic placement. Comparative study of the type species of Scydmaenus Latreille and Clavigeroscydmus revealed no differences in any important structures. Consequently, Clavigeroscydmus is placed as a junior synonym of Scydmaenus s. str. Morphological details of the type species of Scydmaenus and Clavigeroscydmus are illustrated and discussed. PMID- 27395940 TI - Eriomacrotergum flechtmanni n. gen. n. sp. (Trombidiformes: Eriophyidae), a new eriophyoid mite from the cupuacu tree, Theobroma grandiflorum, from northern Brazil. AB - A new eriophyid genus and species, tentatively placed in the Tegonotini, namely Eriomacrotergum flechtmanni n. gen. n. sp., is described from the Amazonian fruit tree cupuacu Theobroma grandiflorum (Willd. Ex Spreng.) K. Schum. (Malvaceae), collected in northern Brazil. The new taxon presents a peculiar morphology in having a large opisthosomal plate and a very reduced prodorsal shield, with ocellar-like structures and scapular setae displaced laterally. Discussion on the most remarkable taxonomic traits is presented as well as similarities of the new genus with other Eriophyidae genera. PMID- 27395941 TI - Review of morphometric measurements used in anuran species descriptions and recommendations for a standardized approach. AB - Standardization and repeatability is at the heart of all scientific research, yet very little literature exists to standardize morphometric measurements within vertebrate groups. This is particularly true for amphibians. Our study attempts to rectify this lack of methodological standardization for the measurement of morphological characters in anurans through an extensive literature survey of 136 species descriptions representing 45 currently recognized families of frogs. The survey revealed 42 morphological measurements represented in five percent or more of the literature reviewed. All measurements are listed by most commonly used name, acronym, and most precise definition, and we provide statistics summarizing the variation in measurement use and description from the surveyed literature. Of these 42 measurements, a subset of 16 were found in the top 75% of all surveyed descriptions and identified as a focal set of recommended measurements in an effort to standardize the morphometric measurements that describe anuran species diversity. Illustrations of these 16 measurements are provided as a visual reference for standardizing their measurement. PMID- 27395942 TI - Hydroporus golestanensis, a new species of the H. longulus group from northern Iran (Coleoptera: Dytiscidae: Hydroporinae). AB - Hydroporus golestanensis sp. nov. from Golestan Province, Iran, is described and illustrated. Based on the distinctly sinuate posterior margin of the metacoxal processes, the new species belongs to the H. longulus species group. Hydroporus golestanensis sp. nov. can be recognised from all the other species in the group by the pitchy-brown colouration of the elytra and by the almost symmetrical male median lobe, with distal third evenly tapering to a pointed apex in ventral view. PMID- 27395943 TI - The genera Isorineloricaria and Aphanotorulus (Siluriformes: Loricariidae)
with description of a new species. AB - We review the complex history of those species included in the Hypostomus emarginatus species complex and recognize them in Isorineloricaria and Aphanotorulus. Isorineloricaria consists of four valid species: I. acuarius n. sp., I. spinosissima, I. tenuicauda, and I. villarsi. Aphanotorulus consists of six valid species: A. ammophilus, A, emarginatus, A. gomesi, A. horridus, A. phrixosoma, and A. unicolor. Plecostomus annae and Hypostoma squalinum are placed in the synonymy of A. emarginatus; Plecostomus biseriatus, P. scopularius, and P. virescens are placed in the synonymy of A. horridus; Plecostomus winzi is placed in the synonymy of I. tenuicauda, and one new species, I. acuarius is described from the Apure River basin of Venezuela. Aphanotoroulus can be distinguished from Isorineloricaria by having caudal peduncles that do not become greatly lengthed with size and that are oval in cross section (vs. caudal peduncle proportions that get proportionately longer with size and that become round in cross section), and by having small dark spots (less than half plate diameter) on a light tan background (vs. spots almost as large as lateral plates on a nearly white background. PMID- 27395944 TI - New Species of Campodeidae (Diplura) from Mexican caves. AB - Six new taxa of Campodeidae (Diplura) are described in the genera Litocampa, Juxtlacampa, Oncinocampa, and Tachycampa. We also redescribe the interesting species Juxtlacampa juxtlahucensis Wygodzinsky, 1944 from Juxtlahuaca cave in Guerrero, Mexico. All of these taxa are cave-dwelling species with more or less noticeable troglobiomorphic features They inhabit the subterranean ecosystem in six limestone massifs and one lava tube cave in the central states of Mexico. Four of these species are included in the "tachycampoide" group and one species in the "podocampoide" group (sensu Bareth & Conde). Nine species already known in Central and South America of the "tachycampoide" group, in such poorly-sampled regions compared with the eight species in the well-sampled Mediterranean region (Ibero-Sardinia and north Africa), suggest an American origin for this group. PMID- 27395945 TI - Tardigrades of the Tree Canopy: Milnesium swansoni sp. nov. (Eutardigrada: Apochela: Milnesiidae) a new species from Kansas, U.S.A. AB - Milnesium swansoni sp. nov. is a new species of Eutardigrada described from the tree canopy in eastern Kansas, USA. This species within the order Apochela, family Milnesiidae, genus Milnesium is distinguished by its smooth cuticle, narrow buccal tube, four peribuccal lamellae, primary claws without accessory points, and a secondary claw configuration of [3-3]-[3-3]. The buccal tube appears to be only half the width of the nominal species Milnesium tardigradum for animals of similar body length. The species adds to the available data for the phylum, and raises questions concerning species distribution. PMID- 27395946 TI - New species and new record of Cerambycidae (Coleoptera) from Mexico, with updates to type depository for two species of Disteniinae. AB - Three new species are described from Mexico belonging to two different subfamilies: Derobrachus moroni (Prioninae); Elytrimitatrix (Grossifemora) nogueirai, and E. (G.) cunninghami (Disteniinae). The new species are illustrated and included in existing keys. A new country record is given for Neomallodon arizonicus (Casey, 1912) (Prioninae). The type depository is corrected for two species of Disteniinae. PMID- 27395947 TI - Globospongicola jiaolongi Jiang, Kou & Li, 2015, a junior subjective synonym of G. spinulatus Komai & Saito, 2006 (Crustacea: Decapoda: Stenopodidea: Spongicolidae). AB - Morphological and genetic analyses both showed that the abundant material of deep sea sponge associated Globospongicola shrimps collected off southwestern Taiwan belongs to the same species as G. spinulatus Komai & Saito, 2006 described from the Southwest Pacific and G. jiaolongi Jiang, Kou & Li, 2015 recently described from the South China Sea. Thus, G. jiaolongi is treated as a junior subjective synonym of G. spinulatus. Moreover, it is confirmed that G. spinulatus inhabits general deep-sea area but not in chemosynthetic environment. PMID- 27395948 TI - Study of the genus Gomphocerippus (Orthoptera, Acridoidea, Acrididae, Gomphocerinae) with a new species from northeast China. AB - A new species Gomphocerippus longipennis Li & Ren sp. nov. of the genus Gomphocerippus Roberts, 1941 is described and illustrated from the most northern region of China. The new species is allied to Gomphocerippus rufus (Linnaeus, 1758), but differs from the latter by length of lateral foveola 3.0 times width, tegmina partially surpassing the apex of hind femur, costal area of tegmina in male 1.5 times of subcostal area in width and media area of tegmina in male 1.2 times cubital area in width. The type specimens are deposited in the Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, Jilin, China. PMID- 27395949 TI - Mallacoota misool, a new species of Maeridae from West Papua (Crustacea: Peracarida: Amphipoda). AB - The new species Mallacoota misool is described from the West Macleur Gulf, West Papua. Mallacoota misool sp. nov. is exceptionally similar to the geographically close M. chandaniae Lowry & Springthorpe, 2005 known from the Gulf of Carpentaria in northern Australia and also reported from the South China Sea. Both species have a massive gnathopod 2 propodus defined by two large teeth. Mallacoota misool sp. nov. has the palm medial surface without a dense bunch of seta, which is present in M. chandaniae. PMID- 27395950 TI - A new species of Paracometes Villiers, 1958 from Panama (Coleoptera, Cerambycidae, Disteniinae). AB - Villiers (1958) described Paracometes (Cerambycidae: Disteniinae) for 11 species from Central and South America, and designated Cometes acutipennis Buquet, 1851 as its type species. Santos-Silva and Martins (2004) synonymized Paracometes with Cometes Lepeletier and Audinet-Serville, 1828. Santos-Silva and Tavakilian (2009a) reinstated Paracometes as a distinct genus and provided a new concept for the genus. According to Santos-Silva and Tavakilian (2009b), Paracometes includes six species distributed in Central and South America. The 7th species for this genus is now described. PMID- 27395951 TI - A new species of Acantholycosa Dahl, 1908 (Araneae: Lycosidae) from the Russian Far East. AB - Acantholycosa Dahl, 1908 is a relatively large genus, comprising 29 species to date (World Spider Catalog 2015). The genus is well delimited; its members are recognized by having 4-6 pairs of ventral spines at leg I, a wide embolus (sometimes with a spine at its base), apical pocket(s) of epigyne separated from fovea, among other characters (cf. Marusik et al. 2004, 2015). Acantholycosa is the among the better known genera of Holarctic Lycosidae due to several revisions and reviews (Kronestedt & Marusik 2002; Marusik et al. 2004, 2015; Marusik & Logunov 2011; Marusik & Omelko 2011). Most Acantholycosa are known from the Altai Sayan mountain system (21 species, of which 17 are local endemics) and the Maritime Province of Russia (6 species, three are local endemics). Although the Russian Far East is well studied, an expedition to the previously unstudied Phalaza Mt. in the south part of Maritime Province revealed a new species closely related to A. azarkinae Marusik & Omelko, 2011. The main goal of this paper is to provide detailed description of this new species. PMID- 27395952 TI - A new genus and twenty new species of Australian jumping plant-lice (Psylloidea: Triozidae) from Eremophila and Myoporum (Scrophulariaceae: Myoporeae). AB - The Triozidae is a diverse, cosmopolitan family of jumping plant-lice (Hemiptera: Psylloidea) from an exceptionally diverse range of plant families, but with few described Australian species. As a direct outcome of the Australian Biological Resources Study Bush Blitz species discovery program, many new Psylloidea from novel host plants in remote localities have been revealed. In this study a new genus Myotrioza Taylor gen. nov. and 20 new species are described from southern and central Australia which also establishes the first host plant records from Eremophila and Myoporum (Scrophulariaceae: Myoporeae). New species, delineated using a combination of morphological and mitochondrial COI sequence data, are: Myotrioza clementsiana sp. nov., M. darwinensis sp. nov., M. desertorum sp. nov., M. eremi sp. nov., M. eremophili sp. nov., M. flindersiana sp.nov., M. gawlerensis sp. nov., M. insularis sp. nov., M. interioris sp. nov., M. interstantis sp. nov., M. longifoliae sp. nov., M. markmitchelli sp. nov., M. myopori sp. nov., M. oppositifoliae sp. nov., M. pantonii sp. nov., M. platycarpi sp. nov., M. remota sp. nov., M. scopariae sp. nov., M. serrulatae sp. nov., and M. telowiensis sp. nov. Genetic divergence data, host associations, biogeographic data, diagnoses and a key to species are presented. Myotrioza appears to be particularly diverse in ephemeral southern Australia, especially in inland Western Australia and South Australia, matching regions of high diversity of the host genera; some species are likely to be short range endemics. PMID- 27395953 TI - Contribution to the knowledge of Turkish stoneflies with annotated catalogue (Insecta: Plecoptera). AB - The stoneflies of Turkey are reviewed providing all known distributions and including new records. Additionally, ecological and biogeographical notes are given. The genus Taeniopteryx Pictet 1841 is reported from Turkey for the first time and 12 species new for the Turkish fauna: Leuctra joosti Braasch 1970, L. kopetdaghi Zhiltzova 1972, Protonemura rauschi Theischinger 1975, P. strandschaensis Braasch & Joost 1972, Nemoura asceta Muranyi 2007, N. cambrica Stephens 1836, N. uncinata Despax 1934, Taeniopteryx caucasica Zhiltzova 1981, Brachyptera risi (Morton 1896), Pontoperla katherinae (Balinsky 1950), Siphonoperla neglecta (Rostock 1881), and Bulgaroperla mirabilis nigrita Zwick 1978. Protonemura bithynica Aubert 1964 and Nemoura turcica Zwick 1972 are recognized as full species. The previously unknown female of Leuctra marilouae Vincon & Sivec 2001 is described. The type locality is also given for each species located in Turkey. The distributions of several rare endemic species are augmented by additional new records (Leuctra aculeata Zwick 1982, L. brachyptera Kazanci 1985, L. karcali Vincon & Sivec 2001, L. kurui Kazanci 1983, L. marilouae Vincon & Sivec 2001, L. sipahilerae Vincon & Sivec 2001, L. theischingeri Vincon & Sivec 2001, Protonemura bacurianica bacurianica Zhiltzova 1957, P. oreas Martynov 1928, P. spinulata Martynov 1928 (first confirmed records from Anatolia), P. triangulata Martynov 1928, Nemoura dromokeryx Theischinger 1976, N. martynovia Claassen 1936, and Brachyptera berkii Kazanci 2001. Several species previously reported only from females are excluded from the Turkish fauna: Leuctra minuta minuta Zhiltzova 1960, L. svanetica Zhiltzova 1960, P. dilatata Martynov 1928. Other species are also excluded from the Turkish fauna: L. fusca fusca (Linnaeus 1758), N. carpathica Illies 1963, Siphonoperla burmeisteri (Pictet 1841), and S. libanica Alouf, 1992. According to literature and our new faunistic data, 117 stonefly taxa representing 7 families and 24 genera are known from Turkey. Among them, 44 are endemic species from Anatolia. PMID- 27395954 TI - A taxonomic revision of the genus Primnoisis Studer [& Wright], 1887 (Coelenterata: Octocorallia: Isididae) using morphological and molecular data. AB - A complete taxonomic revision of the genus Primnoisis (Isididae) is presented herein, based on original type material of all nominal species and additional specimens from deep-water surveys in sub-temperate and Antarctic waters. A multi disciplinary approach was used combining morphological characteristics such as colonial branching patterns, polyp structure, sclerite form and arrangement, together with phylogenetic reconstructions using two mitochondrial gene regions (mtMutS and igr1-cox1). The genus Primnoisis is retained with 7 of the 8 nominal species validated (P. antarctica Wright & Studer, 1889, P. rigida Wright & Studer, 1889, P. ambigua Wright & Studer, 1889, P. delicatula Hickson, 1907, P. fragilis Kukenthal, 1912, P. formosa Gravier, 1913 and P. mimas Bayer & Stefani, 1987), with the eighth (P. sparsa Wright & Studer, 1889), synonymised with P. antarctica. In addition, the species Mopsea gracilis Gravier, 1913 is reassigned to Primnoisis and an additional five new species are described (P. chatham n. sp., P. erymna n. sp., P. millerae n. sp., P. niwa n. sp. and P. tasmani n. sp). Most of the species fell into two clear groups, defined both by morphology and genetic grouping, for which two new sub-genera are proposed (P. (Primnoisis) n. subg. and P. (Delicatisis) n. subg.). Three species, P. ambigua, P. mimas and P. tasmani, could not be placed reliably in either sub-genus due to distinctive morphological features or genetic dissimilarity. It was not possible to confirm the monophyly of the genus due to unresolved relationships with the closely related genus Notisis Gravier, 1913 and an undescribed genus of Mopseinae. PMID- 27395955 TI - The genus Pirenella Gray, 1847 (= Cerithideopsilla Thiele, 1929) (Gastropoda: Potamididae) in the Indo-West Pacific region and Mediterranean Sea. AB - Members of the genus Pirenella are abundant inhabitants of intertidal sedimentary shores, often found in association with mangroves, on the continental margins of the western Pacific and Indian Oceans, and eastern Mediterranean Sea. Until recently, four morphological species were recognised in the tropical Indo-West Pacific region and classified in the genus Cerithideopsilla, while another species occupying the Mediterranean and Indian Ocean was classified as Pirenella conica. Molecular phylogenetic analysis has demonstrated that all these species are congeneric and here it is shown that the valid name for the genus is Pirenella. A recently published molecular study recognised a total of 16 species and the present work is a systematic account of these species. Of the 16, nine are described as new. Other significant nomenclatural acts are: fixation of type species of Pirenella as Pirenella mammillata J.E. Gray, 1847; designation of neotypes for Cerithium alatum Philippi, 1849, Cerithium microptera Kiener, 1841, Cerithium conicum Blainville, 1829, Pirenella mammillata J.E. Gray, 1847 and Murex cingulatus Gmelin, 1791; designation of lectotype for Cerithium retiferum G.B. Sowerby II, 1855. The species accounts include full synonymies, detailed descriptions of shells (based on 831 museum samples), distribution records and maps, reviews of life history, of habitat and of ecology, and some images of radulae. Details of shell sculpture are adequate for the diagnosis of most species. Distorted shells are common in some populations and are suggested to represent parasitised individuals. Some species are pests of fishponds in Southeast Asia and P. conica is the intermediate host of a trematode responsible for the human disease heterophyiasis, while others are threatened by habitat destruction. PMID- 27395956 TI - A review of the genus Pycnoglypta Thomson, 1858 (Staphylinidae, Omaliinae, Omaliini) with notes on related taxa. AB - A review of Pycnoglypta Thomson, 1858, including a redefinition of the genus, is given. Lectotype of Omalium luridum Gyllenhal, 1813 is designated. The seven species of the genus are placed into three species groups, including the new monotypic baicalica group. Dropephylla sibirica (Maklin 1878) comb. nov. is transferred from the genus Pycnoglypta and redescribed; consequently, the Dropephylla sibirica species group, which had been diagnosed before by Gusarov within the genus Pycnoglypta, is reestablished in place of the Dropephylla puella species group erected by Jaszay & Hlavac based on erroneous identification of the nominate species. A new synonymy is established: Dropephylla linearis (Zetterstedt 1828) = D. puella (J. Sahlberg 1880) syn. nov. (=Phyllodrepa puella J. Sahlberg 1880). A key to all species of Pycnoglypta and all Siberian and Far Eastern Dropephylla species is provided. Both male and female genitalia and terminalia as well as other main morphological structures are figured anew; distributional data are provided and mapped for all the species discussed. PMID- 27395957 TI - Living among dragons: A festschrift in honor of Dr. Angelo B. M. Machado on occasion of his 80th birthday (Title page). PMID- 27395958 TI - Living among dragons: A festschrift in honor of Dr. Angelo B. M. Machado on occasion of his 80th birthday (Table of contents). PMID- 27395959 TI - FOREWORD: EDITORS' INTRODUCTION. AB - Since its establishment ZOOTAXA has become not only a rapid journal for zoological systematics but also a respected forum for discussions of all taxonomic matters, and it has gradually attained a distinguished position among other zoological journals by its special issues. These collections of papers treat varied themes such as the Carl Linnaeus legacy (Zhang & Shear 2007, Minelli et al. 2008), cataloguing metazoan life (Zhang 2011, 2013), and promoting and discussing the future of taxonomic sciences, for example modification of the International Code of Zoological Nomenclature (ICZN 2008). For these reasons we offer this special issue to celebrate the fruitful career of the eminent Brazilian researcher Dr. Angelo Barbosa Monteiro Machado ("Professor Angelo" to his friends and colleagues). PMID- 27395960 TI - The dragonfly's face of the multidimensional Dr. Angelo Barbosa Monteiro Machado: a short bio-bibliography. AB - In this special issue celebrating the Brazilian researcher Dr. Angelo Barbosa Monteiro Machado's 80th birthday, I present a very short biographical overview focused on his prolific career as odonatologist. The doctor, professor, children's book writer, conservationist, comedian, neuroanatomist, and eventually odonatologist Professor Angelo has published more than 110 papers, of which 79 are on dragonflies. He erected 97 new names, an impressive number for a small and relatively well-known order of insects. Here are presented annotated checklists of his publications on dragonflies (from 1953 to September of 2015), and nomina, as well as few comments of his impact on Neotropical odonatology as a whole. PMID- 27395961 TI - Psaironeura angeloi, a new species of damselfly (Zygoptera: Coenagrionidae) from Central and South America. AB - Psaironeura angeloi sp. nov. (Holotype male deposited in FSCA: ECUADOR, Esmeraldas Province, small stream 5.6 km NW of Lita, 00.893 degrees N 78.510 degrees W, 4.II.1997, KJT leg.) is described and illustrated based on specimens from Ecuador, Panama, Costa Rica, and Nicaragua, bringing the total number of species in the genus to five. The new species is closely related to P. remissa (Calvert), a Mexican/northern Central American species with broad, foliate male cerci, but is distinct in that the long flagella of the genital ligula lack a small sharp spine unique to P. remissa, labrum and clypeus are orange-red, and the back of the head is mostly pale in both males and females. In life, the eyes of the new species are bright red in males versus green and black in P. remissa. PMID- 27395963 TI - Larva of Palaemnema brasiliensis Machado (Odonata: Platystictidae), from Amazonas, Brazil. AB - The larva of Palaemnema brasiliensis Machado, 2009 is described and illustrated based on last-instar larvae and exuviae of reared larvae collected in a blackwater stream in Barcelos and Presidente Figueiredo municipalities, Amazonas state, Brazil. The larva of P. brasiliensis can be distinguished from the two South American species of the genus with described larvae (P. clementia Selys and P. mutans Calvert), mainly by presence of a single obtuse cusp on the labial palp, the presence and configuration of setae in the caudal lamellae, and the proportional length of terminal filaments of the caudal lamellae. The family is recorded here for the first time in Brazilian state of Amazonas. PMID- 27395962 TI - A taxonomic synopsis of South American Cyanogomphini Carle with description of Cyanogomphus angelomachadoi sp. nov. from the Cerrado of Brazil (Odonata: Gomphidae). AB - A synopsis of Cyanogomphini Carle, 1986 (sensu Belle 1996), including all species currently under the genera Cyanogomphus Selys, 1873, and Tibiagomphus Belle, 1992, is provided. Cyanogomphus angelomachadoi sp. nov. (Holotype ? deposited in DZRJ: Brazil, Minas Gerais State, Jaboticatubas municipality, Parque Nacional da Serra do Cipo, collecting site "Corrego das Pedras" 19 degrees 22'17"S, 43 degrees 36'03"W, 766 m a.s.l., 12.XII.2011, A.P.M. Santos & D.M. Takiya leg.) is described and illustrated based on four males and two females from Minas Gerais and Sao Paulo States, southeastern Brazil. The new species is most similar to C. waltheri Selys, 1873, from which it can be distinguished by its smaller size; larger pale areas on mesepisternum; pale dorsal surface of metathoracic tibia; larger distal concavity on epiproct, with laterodistal projection, in lateral view forefinger-shaped; and occurrence in Cerrado province. Five species are recognized in Cyanogomphini, and for each one a synonymy, diagnoses, identification key and maps of distribution are presented. The status of sibling taxa Tibiagomphus uncatus (Fraser, 1947) and T. noval (Rodrigues Capitulo, 1985), as well as the Agriogomphus-complex of genera are also discussed. PMID- 27395964 TI - Redescription of the larva of Gynacantha cylindrata Karsch (Insecta: Odonata: Aeshnidae). AB - The ultimate stadium larva of Gynacantha cylindrata Karsch, 1891 is described and illustrated based on fifteen male and female exuviae from Bundibugyo, Uganda. The larva resembles those of the few described African species of the genus but shows a denser coverage of spine-like setae on body surface and abundance of hair-like setae on mouthparts. The female gonapophyses appear to be the longest described in the genus up to now and similar to those of G. villosa, a species included in the same group of African species. PMID- 27395965 TI - Geometric morphometrics and molecular systematics of Xanthocnemis sobrina (McLachlan, 1873) (Odonata: Coenagrionidae) and comparison to its congeners. AB - The taxonomy of the damselfly genus Xanthocnemis is revised, with particular focus on populations inhabiting the North Island of New Zealand. Earlier studies revealed two species: X. sobrina, restricted to cool, shaded streams in kauri forests and other forested areas, and X. zealandica, a common species throughout New Zealand except the Chatham and subantarctic islands. A field study encompassing aquatic habitats throughout the whole North Island was carried out to establish the relationship between morphological variation (body size and various morphological traits over the entire body) observed by previous researchers with ecological conditions and/or geographical location. The main aim was to propose reliable diagnostic features that could be used in future studies. Morphological and molecular variation was assessed. Morphological examination included assigning landmarks for all body parts corresponding to the external morphological features that are usually used in Odonata taxonomy. Molecular analysis targeted fragments of the 28S and 16S rRNA genes. Congruence was sought between both types of data, statistical support for two morphological types previously described as different species and a maximum likelihood phylogenetic tree in conjunction with a pairwise genetic distance matrix constructed from the DNA sequences obtained from the sampled specimens. Geometric morphometrics revealed statistically significant differentiation between specimens identified as X. zealandica and X. sobrina for four traits: (1) dorsal view of the head for both sexes as well as male appendages from (2) dorsal, (3) ventral and (4) lateral views. Wings appeared different when analysed for males only. Molecular analysis, however, grouped all specimens into a single undifferentiated cluster with very low mean pairwise distance (<0.01) between them showing almost no variation at the molecular level among the sampled populations on the North Island. Therefore, an additional analysis of the mitochondrial cytochrome c oxidase I gene was carried out comparing randomly selected North Island specimens to Xanthocnemis specimens targeted in other molecular studies (Nolan et al. 2007, Amaya-Perilla et al. 2014). The analysis of the COI gene confirmed that all North and South Island isolates of Xanthocnemis cluster together in a well-supported clade with pairwise identity >96% and ~93% pairwise identity with X. tuanuii sequences obtained from the Chatham Island specimens. A careful investigation of the thin plate spline deformations generated for the geometric morphometric landmarks showed that the significant variations in the appendages of the Xanthocnemis specimens appeared to be the result of size, rather than shape, differences. Therefore, X. sobrina is proposed as a synonym of X. zealandica. Recently Amaya-Perilla et al. (2014) synonymised X. sinclairi with X. zealandica and confirmed the status of the Chatham Island X. tuanuii as a distinct species. It is therefore proposed that the genus Xanthocnemis consists of two species only: zealandica occurring all over the North, South and Stewart Islands, and tuanuii, endemic to Chatham and Pitt islands. Considering several statistical tests involving body measurements and ecological variables recorded during the field study, as well as various discussion points from similar studies of other species of Odonata, two alternative hypotheses are proposed for future testing. The first hypothesis synonymises X. sobrina with X. zealandica and suggests a possible explanation for the evolution of the two morphological traits that have previously been considered diagnostic for these species. The second hypothesis suggests that as typical X. sobrina were not sampled during this study this could represent a species that is now extinct, unless future studies prove it otherwise. PMID- 27395966 TI - A new species of the genus Hermanella Needham & Murphy (Ephemeroptera: Leptophlebiidae) from Northeastern Brazil. AB - Hermanella angeli sp. nov. (Holotype male deposited in MZUSP: Itacare municipality, Cachoeira Bom Sossego, 14 degrees 20'05.2"S, 39 degrees 01'27.4"W, 31.VII.2012, Mariano, R, Almeida, E & Costa, S. leg.) is described based on imagos and nymphs from the State of Bahia, Brazil. The new species can be distinguished by the following combination of characteristics, in male imagos: (1) costal and subcostal area of forewing brown (Fig. 5b); (2) thorax and abdominal terga predominantly brown (Fig. 2-3); (3) penes divided in apical 1/8 (Fig. 8); (4) penis lobe with ventral, long, curved spine (Fig. 7); (5) prosternum narrow (Fig. 1). In nymphs: (1) tarsal claws with 2-3 accessory denticles (Fig. 19); (2) mandible without setae near basal articulation (Fig. 13a); (3) prostheca of left mandible with spines on inner margin (Fig. 13b); (4) plate-like gills terminated in a finger-like process (Fig. 11). PMID- 27395967 TI - Two new species of Ulmeritoides Traver (Ephemeroptera: Leptophlebiidae) from Southeastern Brazil. AB - Two new species of Ulmeritoides Traver, 1959 are described from Southeastern Brazil based on male and female imagos. Ulmeritoides angelus sp. nov. (Holotype male deposited in DZRJ: Minas Gerais State) differs from all other species of the genus by the following combination of characters: forewings hyaline, base dark brown and purplish; veins R1 light brown; dark brown spots on bullae of veins Sc and R2; apex of penis lobes somewhat rounded, each with one central spine. Ulmeritoides tamoio sp. nov. (Holotype male deposited in DZRJ: Sao Paulo State) differs from all other species of the genus by the following combination of characters: wings hyaline; veins C, Sc and R1 brownish; brownish spots on bullae of veins Sc and R2; apex of penis lobes straight, ending in rather acute apical and mesal projections. An updated key to the genera Ulmeritoides Traver, 1956 and Ulmeritus Traver, 1956 is also given. PMID- 27395968 TI - First record of Segonalia Young (Hemiptera: Cicadellidae: Cicadellinae) from Brazil including the description of S. machadoi sp. nov. AB - Segonalia, a previously monotypic genus known from Bolivia, is newly recorded from Brazil and Paraguay based on specimens of S. steinbachi Young, 1977 from Minas Gerais State, Brazil and Paraguay and a new species from Piaui and Para States, Brazil. Segonalia machadoi sp. nov. (Holotype male deposited in CZMA: Brasil, Piaui State, Parque Nacional de Sete Cidades, 045'57"S, 4142'34"W 193 m a.s.l., 12.II.2013, D.M. Takiya leg.) can be distinguished from the type species by its body length and shape of the male pygofer apex and aedeagus. A diagnosis of Segonalia and comparative notes and illustrations of the type species are given. PMID- 27395969 TI - Two new species of the Neotropical spittlebug genus Monecphora Amyot & Serville (Hemiptera: Cercopidae) with key and notes of species of the genus. AB - Two new species of the Neotropical spittlebug genus Monecphora Amyot & Serville are described: Monecphora machadoi sp. nov. (Holotype male deposited in NMW: Brazil, "Natterer") and Monecphora broomfieldi sp. nov. (Holotype male deposited in BMNH: Costa Rica, Turrialba, 3-8.VII.1981, W.R. Dolling leg.) and a key and notes to species of the genus are provided. Lectotypes are designated for Tomaspis fryi Distant, Monecphora nigritarsis Stal, and Monecphora semilutea Stal. In addition, two corrections are made to the Cercopid Spittlebugs of the New World (Carvalho & Webb 2005) with respect to figures 70-73 and 193-194 (see Corrigenda). PMID- 27395970 TI - A new species and new records of Oiovelia (Heteroptera: Gerromorpha: Veliidae) from Brazil. AB - Oiovelia currently comprises eight species and has been recorded only from South America. Here, the ninth species, Oiovelia machadoi sp. nov. (Holotype male deposited in MZUSP: BRAZIL, Sao Paulo State, Biritiba Mirim, Parque Estadual da Serra do Mar, 23 degrees 42'16.4"S, 46 degrees 02'42.8"W, 725 m a.s.l., 23.VIII.2014, H. Rodrigues leg.), is described and illustrated based on specimens from the Atlantic Forest, Southeastern Brazil. The new species can be distinguished from all other species in this genus mainly by the dark color of the body, absence of the V-shaped pruinosity on the posterior lobe of pronotum, well-defined pruinosity between the cells of the forewing, and presence of a pair of spines on the proctiger. In addition, important intraspecific variations in a population of O. brasiliensis from the State of Sao Paulo are presented. Finally, the genus is recorded for the first time from Northeastern Brazil based on specimens of O. cunucunumana and O. viannai collected in the State of Bahia. PMID- 27395971 TI - There and back again: contributions on Pseudevoplitus Ruckes (Heteroptera: Pentatomidae). AB - Pseudevoplitus Ruckes was recently revised and new species were described. The genus has a Neotropical distribution, with species mainly found in the Amazon. Here, we describe the previously unknown female of P. roraimensis and add localities to its known distribution. Also, a new species, P. angelomachadoi sp. nov. (Holotype male deposited in MNHN: French Guiana, Acarouany, 15.IX.1998, A. Matocq leg.), from the Amazonia of French Guiana is described; it can be distinguished from other species of the genus mainly by the bell-shaped pygophore in males, and the gonocoxites 8 widely obscuring the laterotergites 8 basally, in females, a unique character of this species. The key to species of Pseudevoplitus is updated to include the new species and females. PMID- 27395972 TI - Unusual looking pentatomids: reassessing the taxonomy of Braunus Distant and Lojus McDonald (Hemiptera: Heteroptera: Pentatomidae). AB - The Neotropical genus Braunus Distant is revised. Based on general morphology, Braunus is transferred to the Pentatominae and Lojus is proposed as a junior synonym of Braunus. The male and female genitalia of Braunus sciocorinus (Walker) are described for the first time. Three new species from the Peruvian and Bolivian Andes and from Colombia are described, Braunus machadoi Barao & Garbelotto sp. nov. (Holotype male deposited in AMNH: Peru, Cuzco, 01.XII.2011, C. Weirauch leg.), Braunus gibbus Garbelotto & Barao sp. nov. (Holotype female deposited in AMNH: Bolivia, Santa Cruz, Prov. Caballero, 15-21.X.2001, S. Spector & J. Ledezma leg.), and Braunus prionotus Barao & Garbelotto sp. nov. (Holotype female deposited in MNHN: Colombia, VII.1974, Steinheil leg.), respectively. Also, we describe the internal male and female genitalia of Braunus ocellatus (Thomas) comb. nov. A key to species and comments on subfamilial and tribal placements and on wing polymorphism are provided. PMID- 27395973 TI - New species and records of Oukuriella Epler, 1986 from the Neotropical region (Diptera: Chironomidae). AB - Two new species of Oukuriella, O. angelomachadoi sp. nov. (Holotype male deposited in MZUSP: BRAZIL, Parana State) and O. plumaterata sp. nov. (Holotype male deposited in MZUSP: BRAZIL, Sao Paulo State), and the immatures stages of O. sublettei are described and figured. The larvae of O. sublettei were collected from submerged woods in low-order streams in the Atlantic Forest. In addition new records of several described species, including the first records of Oukuriella from Mexico and Bolivia are given. PMID- 27395974 TI - Two new species of Microlia Casey (Coleoptera: Staphylinidae) with comments on obligatory pollen-feeders and the first record from South America. AB - Microlia Casey, 1910 is a small genus that currently includes twelve species distributed in Australasian and New World regions. Here, two new species of Microlia-M. amici sp. nov. (holotype male deposited in DZUP: Brazil, Parana State) and M. machadoi sp. nov. (holotype male deposited in DZUP: Brazil, Rio Grande do Sul State)-are described and illustrated. M. amici sp. nov. differs from M. meticola by abdominal segments darker, mesotarsus with 5 segments, tergum VII of male without tubercles, and tergum VIII of male emarginated in posterior margin. While, M. machadoi sp. nov. differs from M. pentamera and M. tetramera by curved spine-like in the posterior margin of tergum III. Additional comments on their pollen-feeders habits that are available from morphological and natural history data, and the distribution of the genus is extended in the New World, now including the first time record for South America. PMID- 27395975 TI - Two new species of Omalodes from Dominican Republic (Coleoptera: Histeridae). AB - Omalodes Dejean, 1833 is the largest genus of Omalodini, with approximately 63 species described in three subgenera with an exclusively Neotropical distribution. Currently there are only two described species for the Caribbean, both of the subgenus Omalodes, and among other species they are the only ones with complete apical stria on the elytra. Two new species of this subgenus: Omalodes angelo sp. nov. (Holotype male deposited in FSCA: Dominican Republic, Monte Cristi Prov.) and Omalodes kovariki sp. nov. (Holotype male deposited in USNM: Dominican Republic, Monte Cristi Prov.) are described. Both species present a complete apical stria on the elytra and a superficial sulcus or impression on the frons. The lateral pronotal punctures are more evident in O. angelo sp. nov. while in O. kovariki sp. nov. they are weaker, only slightly more evident than the ground punctures. Both species have the punctures of the propygidium somewhat sparse. However, in O. angelo sp. nov. the punctures are limited to the sides and slightly in the middle anteriorly. Omalodes kovariki sp. nov. have a wide glandular opening posterad to metacoxae, a character not registered before for the genus. PMID- 27395976 TI - A new brachypterous genus of Brazilian stag beetle (Coleoptera: Lucanidae: Lucaninae) with description of three new species. AB - Montesinus gen. nov. is described from Brazil, along with three new species, Montesinus monnei sp. nov. (Holotype male deposited in MNRJ: Brazil, Espirito Santo State, Parque Nacional do Caparao, 2500 m a.s.l., 13.IV.2001, F.O. Correia leg.), M. tatula sp. nov. (Holotype female deposited in CERPE: Brazil, Minas Gerais State, Corinto, 900 m a.s.l., I.1998, E. Antunes leg.), and M. machadoi sp. nov. (Holotype female deposited in MNRJ: Brazil, Espirito Santo State, Serra do Caparao, Ibitirama, 2600 m a.s.l., 10-12.IV.2012, M.V.P. Simoes leg.). This unusual genus is related to Altitatiayus Weinreich, with which it shares the brachypterous condition and also some characters of the male genitalia, being distinguished from it mainly by its punctate flat head and indistinct elytral striae. The three new species are distinguished by their general color, shape of posterior margin of pronotum, tibial armature and elytral punctures. The new species are from two isolated mountain formations, called Serra do Caparao and Serra do Espinhaco formations. This is the third brachypterous genus of stag beetle found in Brazil, but it occurs in mountains isolated from the Serra da Mantiqueira where the other two genera are found. The habitus, male genitalia and maxillae of the new species are illustrated. PMID- 27395977 TI - Taxonomic review of the Dichotomius (Luederwaldtinia) assifer (Eschscholtz) species-group (Coleoptera: Scarabaeidae). AB - The Dichotomius assifer species-group, a component of Dichotomius (Luederwaldtinia) is taxonomically revised. The group now contains five species: D. angeloi sp. nov. (Holotype male deposited in CEMT: BRAZIL, Minas Gerais State, Vargem Bonita, Parque Nacional Serra da Canastra. Mata de Galeria, 28o18'39"S, 46o31'30"W. 865 m a.s.l., 02.XI.2011, MF Souza leg.), and D. louzadai sp. nov. (Holotype male deposited in CEMT: BRAZIL, Minas Gerais State, Lima Duarte, Parque Estadual Ibitipoca, VI.2001, FZ Vaz-de-Mello leg.) are described; D. assifer and D. affinis are redescribed and lectotypes are designated. D. machadoi is diagnosed. Illustrations, distributional records, diagnosis and a key for identification of the species in the group are provided. Some aspects of the natural history and biogeography of species in the assifer group are also discussed. PMID- 27395978 TI - Two new species of Cyclocephala (Coleoptera: Scarabaeoidea: Melolonthidae) from Minas Gerais State, Brazil. AB - Two new species of Cyclocephala constituting a new species group in the genus, Cyclocephala machadoi sp. nov. (Holotype male deposited in CERPE: Brazil, Minas Gerais State, Sao Goncalo do Rio Preto municipality, Parque Estadual do Rio Preto) and C. everardoi sp. nov. (Holotype male deposited in CERPE: Brazil, Minas Gerais State, 8 km north of Cristalia municipality), are here described and illustrated. The only two males known were collected with light traps and have antennal lamellae much larger than other South American species, along with large eyes and a quadrate narrow clypeal apex. PMID- 27395979 TI - New species and records of Menoscelis Mulsant (Coleoptera: Coccinellidae) from French Guiana. AB - Three new species of Menoscelis Mulsant, 1850 from French Guiana are described: Menoscelis angeloi sp. nov. (Holotype male deposited in MNHN: Point de vue du Belvedere de Saul, 09.IX.2011, SEAG col.), M. cordata sp. nov. (Holotype female deposited in MNHN: Reserve Naturelle des Nouragues-Saut Parare 04o02'N, 52o41'W, 08.IX.2009, SEAG col.) and M. flava sp. nov. (Holotype female deposited in MNHN: Montagne des Chevaux 04o44'56"N, 02o26'28"W, 14.I.2012, SLAM, SEAG col.). The male of M. insignis Mulsant is described, and an identification key to the species of Menoscelis is included. New geographic distribution records, maps and a checklist of the species are also provided. PMID- 27395980 TI - Two new species of Chnoodes Chevrolat (Coleoptera: Coccinellidae) from Brazil. AB - Two new species of Chnoodes from Brazil are described: C. machadoi sp. nov. (Holotype male deposited in DZUP: Mato Grosso State, Caceres muncipality, 13.XI.1984, Buzzi, Mielke, Elias & Casagrande leg.) and C. unimaculata sp. nov. (Holotype female deposited in DZUP: Amapa State, Oiapoque municipality, V.1959, M. Alvarenga leg.). They can be distinguished from all previously described species mainly by the yellowish border of the elytra in C. machadoi sp. nov., and the large mid-dorsal pale spots in C. unimaculata sp. nov. Six species are redescribed: Chnoodes brasiliensis Korschefsky, C. chaudoiri Mulsant, C. discomaculata (Crotch), C. pentagona Crotch, C. pseudosanguinea Brethes, and C. tarsalis Weise. A key to Brazilian species of Chnoodes and new records are also given. PMID- 27395981 TI - A key to American genus Merobruchus Bridwell (Coleoptera: Chrysomelidae: Bruchinae) with descriptions of species and two new host plant records for the subfamily. AB - Merobruchus Bridwell is placed in the group Merobruchus of Acanthoscelidina (Bruchini) being distinguished from all bruchines mainly by the apical projections in the last abdominal ventrite of females and some males. All 25 species of Merobruchus are distributed in the New World, mainly in the Neotropical Region, feeding on seeds of Mimosoideae (Acacieae, Ingeae and Mimoseae). As well as some other bruchine genera, Merobruchus shows considerable morphological variation both in external and in internal (male genitalia) characters. Moreover, some species are very similar to each other in their colour and distribution pattern of pubescence on the dorsal surface, sometimes making species recognition difficult. Thus, the main objective of this paper is to provide a key including coloured illustrations for Merobruchus species to facilitate the process of identification and to avoid misunderstandings. Images of dorsal habitus, male and female pygidium and male genitalia are provided for all species. In addition, M. machadoi sp. nov. (Holotype male deposited in DZUP: Brazil, Rio Grande do Sul State) is described; M. bicoloripes (Pic) and M. pickeli (Pic) are redescribed; and a new synonymy is proposed: Pseudopachymerus pickeli Pic, 1927 = Pseudopachymerus pickeli var. subnotatus Pic, 1927 syn. nov. Two new host plants are recorded for Bruchinae: Parapiptadenia rigida (Benth.) Brenan (Mimosoideae) and Pterogyne nitens Tul. (Caesalpinioideae). PMID- 27395982 TI - Five new species, one new genus, two synonymies, and new distributional records in Cerambycidae (Coleoptera). AB - Five new species, and one new genus of Cerambycidae are described: Drycothaea vulcanica sp. nov. (Calliini), from Ecuador (Holotype male deposited in AMNH: Napo, 29.X.1988, J.S. Miller leg.); Perissomerus machadoi sp. nov. (Neoibidionini), from Paraguay (Holotype male deposited in MZSP: Alto Paraguay, 30.XI.2002, Di Iorio leg.); Cacostola carinata sp. nov. (Onciderini), from Brazil (Holotype female deposited in MZSP: Rio Grande do Norte, IX.2008, D.R.R. Fernandes et al. leg.); Ypomacena gen. nov. (Apomecynini) from Brazil to include Y. monnei sp. nov. (Holotype male deposited in MNRJ: Bahia, XI.1970, Roppa leg.), and Y. gibbosa sp. nov. (Holotype female deposited in MNRJ: Rio de Janeiro, 31.X.1969, Alvarenga & Seabra leg.). Dorcasta prolongata Fisher, 1947 is proposed as a new synonym of Bebelis lignea (Bates, 1866). Bisaltes (Bisaltes) fuchsi Breuning, 1971 is proposed as a new synonym of Bisaltes (Bisaltes) buquetii Thomson, 1868. Additionally, sixteen new states records for Brazil, and three country records for Bolivia are provided. PMID- 27395983 TI - A new species of Chimarra (Otarrha) Blahnik from Brazil (Trichoptera: Philopotamidae). AB - Chimarra Stephens, 1829 is the second largest genus of Trichoptera, with more than 700 extant species worldwide (Morse 2015). Currently 4 subgenera are recognized: Chimarra Stephens, 1829, known from all zoogeographic regions; and Curgia Walker, 1860, Chimarrita Blahnik, 1997, and Otarrha Blahnik, 2002, all of them confined to the Neotropics (Blahnik & Holzenthal 2012). PMID- 27395984 TI - Three new species of Stactobiinae (Trichoptera: Hydroptilidae) with the first record of Orinocotrichia Harris, Flint & Holzenthal from Brazil. AB - Approximately 300 species are assigned to Stactobiinae, most of them occurring in the Old World. Seven species have been recorded from Brazil, six of Flintiella and one of Bredinia. Herein, three new species are described and illustrated based on specimens collected in Maranhao and Piaui states from Northeastern Region of Brazil: Orinocotrichia angelus sp. nov. (Holotype male deposited in CZMA: Maranhao State) can be distinguished by the subgenital plate conspicuous, mesally divided; Flintiella pallida sp. nov. (Holotype male deposited in CZMA: Maranhao State), differs from its cogeners by the process of the subgenital plate; and F. harrisi sp. nov. (Holotype male deposited in CZMA: Piaui State), recognized by the short process of the phallus. The new species of Orinocotrichia is the third species described in this genus and represents the first record of Orinocotrichia from Brazil. Orinocotrichia angelus sp. nov. and F. pallida sp. nov. are the first microcaddisflies species described from Maranhao State, Brazil. PMID- 27395985 TI - Three new species of Helicopsyche von Siebold (Trichoptera: Helicopsychidae) from Brazil. AB - Three new species of Helicopsyche subgenus Feropsyche (Trichoptera: Helicopsychidae) from southern and southeastern Brazil are diagnosed, described, and illustrated: Helicopsyche angeloi sp. nov. (Holotype male deposited in MZSP: Minas Gerais, Rio de Janeiro and Sao Paulo States), H. guara sp. nov. (Holotype male deposited in MZSP: Minas Gerais and Santa Catarina States) and H. lazzariae sp. nov. (Holotype male in MZSP: Parana State). The first two species are similar to H. cipoensis Johanson & Malm, 2006, and H. timbira Silva, Santos & Nessimian, 2014, in having similarly shaped inferior appendages. However, the new species differs in the morphology and distribution of setae on the inferior appendages and tergum X. Helicopsyche lazzariae sp. nov. is unlike any other described species in the subgenus Feropsyche because of its broad deltoid-shaped inferior appendage and absence of a basomesal process on the inferior appendage. Characters important for diagnosing and describing new species of Helicopsyche (Feropsyche) are discussed. Finally, an updated checklist of the 23 species recorded for Brazil is presented. PMID- 27395986 TI - Description of three new species of Galethalea Butler, 1876 (Lepidoptera: Erebidae), with comments on the genus. AB - Galethalea portoricensis sp. nov. (Holotype male deposited in SMNS: Puerto Rico, 20.iii.1974, W. Plathsr. leg.), G. wolfei sp. nov. (Holotype male deposited in LACM: Colombia, 1.iv.1995, K. Wolfe et al. leg.), and G. machadoi sp. nov. (Holotype male deposited in SMNS: Ecuador, 23.x.2000, G. Brehm leg.) are described, all known only from males. G. machadoi sp. nov. and G. wolfei sp. nov. seem to be closely related to G. davidi Dognin, 1889 resur. stat., while G. portoricensis sp. nov. seems closer to the type species, G. pica (Walker, 1854). The three new species, plus G. davidi, are illustrated in habitus and genitalia, and comments on the genus Galethalea are provided, along with a key to the species currently placed in this genus. PMID- 27395987 TI - Taxonomic revision of the "Pierella lamia species group" (Lepidoptera: Nymphalidae: Satyrinae) with descriptions of four new species from Brazil. AB - Four new species of Pierella Westwood, 1851 from Brazil are described: P. angeloi Zacca, Siewert & Mielke sp. nov. from Maranhao, P. kesselringi Zacca, Siewert & Paluch sp. nov. from Paraiba, Pernambuco, Alagoas and Sergipe, P. nice Zacca, Siewert & Paluch sp. nov. from Bahia and P. keithbrowni Siewert, Zacca & Casagrande sp. nov. from Bahia, Espirito Santo, Rio de Janeiro, Sao Paulo, Parana and Santa Catarina. Additionally, P. chalybaea Godman, 1905 stat. rest. and P. boliviana F.M. Brown, 1948 stat. nov. are recognized as valid species and not as subspecies of P. lamia (Sulzer, 1776), while P. l. colombiana Constantino & Salazar, 2007 syn. nov. is synonymized to the former. Lectotype and paralectotype of Papilio dyndimene Cramer, 1779 (a synonym of Pierella lamia) and Pierella chalybaea Godman, 1905 stat. rest. are designated. Habitus and illustrations of male and female genitalia are provided for all species, as well as a geographical distribution map. PMID- 27395988 TI - Taxonomic investigations on the Braconinae fauna (Hymenoptera, Braconidae) in north-eastern Anatolian region, Turkey, with the description of a new species. AB - Adult specimens of Braconinae were collected from various habitats of Ardahan, Erzurum, Igdir and Kars of the Turkish north-eastern Anatolian region between 2011 and 2014. In total, 87 species belonging nine genera are reported for the region among which 10 are recorded for the first time from Turkey: Bracon (Bracon) rhinchiti Greese, 1928, Bracon (Bracon) murgabensis Tobias, 1957, Bracon (Bracon) querceus Tobias, 1986, Bracon (Glabrobracon) karakumicus Tobias, 1967, Bracon (Lucobracon) hylobii Ratzeburg, 1848, Bracon (Lucobracon) irkutensis Telenga, 1936, Bracon (Orthobracon) longiantennatus Tobias, 1957, Bracon (Orthobracon) longigenis Tobias, 1957, Coeloides sordidator (Ratzeburg, 1844) and Glyptomorpha (Glyptomorpha) dispar Tobias, 1986. As well, Bracon (Bracon) selviae sp.n. is described. Thiss brings the total number of species of Turkish Braconinae recorded to 205. The known hosts of each species are also provided. PMID- 27395989 TI - Caligus lini n.sp., a new caligid (Copepoda, Siphonostomatoida) parasitic on the brilliant pomfret Eumegistus illustris Jordan & Jordan (Perciformes, Bramidae) of Taiwan. AB - Caligus lini n.sp., a new species of caligid copepod parasitic on the gill rakers and caudal fin of the brilliant pomfret, Eumegistus illustris Jordan & Jordan (Perciformes, Bramidae), is described from fish caught off Tai-Dong, Taiwan. The new species differs from its congeners by its possession of the following, unique combination of features: (1) middle two elements at the tip of leg 1 simple (without accessory process), (2) innermost element shortest and smallest of the four terminal elements on leg 1, (3) leg 4 exopod with an armature formula of I,III, and (4) complex leg 5 represented by 2 seta-bearing processes, a simple anterior process tipped with 1 plumose seta and quadripartite posterior process carrying 3 setae (1 simple and 2 plumose). The new species differs from its closest congener, Caligus tylosuri (Rangnekar, 1956), in the structure of the middle two elements (simple without carrying accessory process) at the tip of leg 1 and a quadripartite (instead of tripartite) posterior process on leg 5. PMID- 27395990 TI - Nephtys bangladeshi n. sp., a new species of Nephtyidae (Annelida: Phyllodocida) from Bangladesh coastal waters. AB - A new species of nephtyid polychaete, Nephtys bangladeshi n. sp., from the intertidal zone of Bangladesh is described. It is characterized by having a pharynx with 9 pairs of bifid terminal and 14 rows of subterminal papillae, each subterminal row with 5-7 papillae, as well as the presence of branchiae from chaetiger 7 to 27. The new species is compared with other species from the Indo Pacific. This is the first report of a new polychaete species from Bangladesh coastal waters. PMID- 27395991 TI - The genus Brechmorhoga Kirby, 1894, in the West Indies, with a proposed new status for Brechmorhoga archboldi (Donnelly) (Odonata; Libellulidae). AB - A revision of the species of Brechmorhoga from the Lesser Antilles includes Brechmorhoga archboldi (Donnelly, 1970) and Brechmorhoga praecox grenadensis Kirby, 1894. New distribution records are provided. Brechmorhoga archboldi is synonymized with B. praecox grenadensis. Figures, morphological characters of both sexes and the description of the female of B. p. grenadensis are given. PMID- 27395992 TI - Taxonomy and bathymetric distribution of the outer neritic/upper bathyal ostracodes (Crustacea: Ostracoda) from the southernmost Brazilian continental margin. AB - Sixty-five ostracode species belonging to 41 genera and 17 families were recorded in the outer shelf and upper slope off Rio Grande do Sul and Santa Catarina states, southernmost Brazil, between 100 and 586 m water depth interval. The ostracode occurrences are hypothesized to be influenced by both, the coastal waters and the Antarctic Intermediate Water (AAIW). The taxonomy of some species of Bradleya Hornibrook, 1952, Legitimocythere Coles & Whatley, 1989 and Henryhowella Puri, 1957 previously described in the same study area is revised. Bradleya gaucha sp. nov., Legitimocythere megapotamica sp. nov., Apatihowella acelos sp. nov., Apatihowella capitulum sp. nov., Apatihowella besnardi sp. nov., Apatihowella convexa sp. nov., and Aversovalva tomcronini sp. nov. are herein proposed. Trachyleberis aorata Bergue & Coimbra, 2008 is reassigned to the genus Legitimocythere and Bradleya pseudonormani Ramos et al., 2009 has its diagnosis emended. Bythocypris praerenis Brandao, 2008 is considered a junior synonym of Bythocypris kyamos Whatley et al., 1998a. Apatihowella Jellinek & Swanson, 2003 and Legitimocythere species have well-defined bathymetric distributions and are potential paleoceanographic markers for the Quaternary in the Southern Brazilian Margin. PMID- 27395993 TI - A new species of karst-dwelling bent-toed gecko (Squamata: Gekkonidae) from Khammouane Province, central Laos. AB - We describe a new species of the genus Cyrtodactylus from Khammouane Province, central Laos based on morphological features and molecular data. Morphologically, Cyrtodactylus bansocensis sp. nov. is differentiated from other congeners by a unique combination of the following characters: medium size, SVL reaching 74.0 mm; dorsal pattern consisting of four light transverse bands between limb insertions; supranasals in contact with each other; dorsal tubercles at midbody in 14-15 irregular rows; lateral folds present without interspersed tubercles; ventral scales between ventrolateral folds 34-35; precloacal and femoral pores in males 34, separated by four poreless scales in the male holotype and in a continuous row in the male paratype; enlarged femoral and precloacal scales present; postcloacal tubercles 5-7 on each side; dorsal tubercles present at tail base; and subcaudal scales transversely enlarged. Molecular analyses revealed the new species to be closely related to Cyrtodactylus rufford, which is also found in Khammouane Province. PMID- 27395994 TI - Re-description of Margarinotus (Paralister) longus (Bickhardt, 1910) with a key to the species of the subgenus Paralister of the genus Margarinotus from the Balkans (Coleoptera, Histeridae, Histerinae). AB - The holotype of Margarinotus (Paralister) longus (Bickhardt, 1910) is re described and figured. A key to the species of the subgenus Paralister Bickhardt, 1917 of the genus Margarinotus Marseul, 1853 from the Balkans is given. PMID- 27395995 TI - Redescription of the South African millipede Cylichnogaster lawrencei Verhoeff, 1937 and notes on the family Siphonotidae (Diplopoda, Polyzoniida). AB - The unusual millipede Cylichnogaster lawrencei Verhoeff, 1937 (Diplopoda, Polyzoniida, Siphonotidae) is redescribed from newly collected specimens. Species of Cylichnogaster are the only known colobognathan millipedes capable of volvation, and are also distinguished by their small size and low segment number. Taxonomic notes are provided on the poorly known family Siphonotidae. PMID- 27395996 TI - A new species of Pseudochydorus Fryer, 1968 (Cladocera: Anomopoda: Chydoridae) from South-East Asia. AB - A new species of genus Pseudochydorus Fryer, 1968 (Cladocera: Anomopoda: Chydoridae) is described from South-East Asia. P. bopingi sp. nov. differs from Palearctic P. globosus (Baird, 1843) by a smaller size, well-developed flattened flange along the posterior margin of the valves, shorter rostrum, smaller ocellus, and details of antenna and thoracic limb II morphology. P. bopingi sp. nov. is known from South China and South Vietnam, but probably has a wider distribution. Our results suggest that populations from outside of Palearctic may belong to separate species as well. PMID- 27395997 TI - On the taxonomic status of Ichthyophis husaini Pillai & Ravichandran, 1999 (Amphibia: Gymnophiona: Ichthyophiidae). AB - Extensive surveys at and around the type locality of Ichthyophis husaini Pillai & Ravichandran, 1999 (an 'unstriped' Ichthyophis) in North East India between 2008 and 2014 yielded tens of striped but no unstriped specimens of Ichthyophis. Contrary to the original description, we observed a lateral stripe on the holotype of I. husaini. The holotype of I. husaini is very similar to the holotype of the striped species I. garoensis Pillai & Ravichandran, 1999, which was collected from a locality only 20 km away from the type locality of I. husaini. The holotypes of these two species are also very similar to 12 newly collected specimens of striped Ichthyophis from this area. We conclude that the holotypes of I. husaini and I. garoensis represent but a single species, and we designate Ichthyophis husaini Pillai & Ravichandran, 1999 as a junior subjective synonym of Ichthyophis garoensis Pillai & Ravichandran, 1999. This taxonomic action and newly reported material extends the known geographic range of I. garoensis. It also reduces the number of Ichthyophis species of North East India to eight, and restricts unstriped members of the genus within this region to a single species (I. sikkimensis Taylor, 1960) that is known only from the far west of the region. PMID- 27395998 TI - One new and three known species of Geocenamus Thorne & Malek, 1968
(Nematoda: Merliniidae) from Iran. AB - Soil samples collected from different plants and localities in Iran yielded one new and three known species of the genus Geocenamus with tessellated cuticle. Geocenamus conicaudatus n. sp. is characterised by a hemispherical cephalic region, set-off from the rest of body by a constriction, a slender stylet 17-20 um long with laterally directed knobs, coarsely annulated cuticle with 32-34 longitudinal striae and a conical tail with smooth, finely rounded terminus. Morphological and molecular studies on the populations of G. paniculoides and G. tartuensis indicated that G. paniculoides may be considered as a valid species. Intraspecific variability of some characters of 30 Iranian populations of G. rugosus were studied. An identification key to 32 valid species of the genus Geocenamus is given. PMID- 27395999 TI - A checklist of the family Pratylenchidae Thorne, 1949 from Iran. AB - The Family Pratylenchidae comprises nematodes that are capable of penetrating and feeding on internal root tissues. The list of Pratylenchidae species known from Iran is presented. The updated species list provides information on their morphometrics, referring to full or partial descriptions, associated plants, geographical distribution and references. The list includes 37 species belonging to five genera. Two species of Pratylenchus (P. sensillatus and P. wescolagricus) are new records for the Iranian nematofauna. Some information on these two and other known species is also provided. PMID- 27396000 TI - Brenthia yangi sp. nov. and its immature stages (Lepidoptera: Choreutidae: Brenthiinae). AB - Brenthia yangi sp. nov. and its immature stages are described. The host plants of the new species are Grewia biloba G. Don and its variety parviflora Hand. -Mazz (Malvaceae). The preference for the position of escape holes in the larvae of the new species is revealed by statistical analysis. Larvae of I-II instar have no significant preference for the position of escape holes, whereas larvae of III-V instar significantly prefer to set escape holes along main veins. The size of silken pillar determines the position of escape holes in III-V instar larvae. The corner of two veins is not always the most preferred position for III-V instar larvae. PMID- 27396001 TI - Two new species of Dicranocentrus Schott, 1893 (Collembola:Entomobryidae) from Serra do Gandarela, Minas Gerais State, Brazil. AB - Two new species of Dicranocentrus from Southeastern Brazil are described: D. melinus sp. nov. and D. cuprum sp. nov., both from "Parque Nacional da Serra do Gandarela" (Minas Gerais State), Brazil. These species can be included to gracilis-group due to the absence of chaeta A1, S2, Ps and up to 6+6 chaetae P on dorsal head. A male genital plate is for the first time illustrated for the genus. PMID- 27396002 TI - Bridging the gap between chewing and sucking in the hemipteroid insects:
new insights from Cretaceous amber. AB - The diversity of feeding apparatuses in insects far exceeds that observed in any other animal group. Consequently, tracking mouthpart innovation in insects is one of the keys toward understanding their diversification. In hemipteroid insects (clade Paraneoptera or Acercaria: lice, thrips, aphids, cicadas, bugs, etc.), the transition from chewing to piercing-and-sucking mouthparts is widely regarded as the turning point that enabled hyperdiversification of the Hemiptera, the fifth largest insect order. However, the transitional process from chewing to piercing and-sucking in the Paraneoptera was hitherto completely unknown. In this paper, we report a well preserved mid Cretaceous amber fossil of the paraneopteran insect family Archipsyllidae and describe it as Mydiognathus eviohlhoffae gen. et sp. n. This species has elongate mandibles and styliform laciniae similar to Hemiptera but retains functional chewing mouthparts. A number of morphological characters place the Archipsyllidae as the sister group of the thrips plus hemipterans, which strongly suggests that the mouthparts of M. eviohlhoffae represent a transitional condition from primitive chewing to derived piercing-and sucking mouthparts. The clade composed of Archipsyllidae, thrips, and hemipterans is here named Pancondylognatha, a new supra-ordinal taxon. Based on newly obtained information, we also assess the monophyly of the Paraneoptera, which was called into question by recent phylogenomic analyses. A phylogenetic analysis that includes Mydiognathus strongly supports the monophyly of the Paraneoptera. PMID- 27396003 TI - Large branchiopod (Crustacea: Branchiopoda) egg morphology of Western Ghats, Maharashtra, India. AB - The eggs of many large branchiopods have taxonomic value and are commonly used as traits in species and/or generic descriptions. In this paper we present detailed descriptions and SEMs of resting eggs of seven of the eight species of large branchiopods found in the Western Ghats of Maharashtra, India. We highlight the inter- and intrapopulation egg morphological variation in Streptocephalus. PMID- 27396004 TI - One new genus and three new species of deep-sea nematodes (Nematoda: Microlaimidae) from the Southwest Pacific Ocean and Ross Sea. AB - New deep-sea nematodes of the family Microlaimidae are described from the Southwest Pacific Ocean and Ross Sea. Microlaimus korari n. sp. is characterised by annulated cuticle with longitudinal bars, round amphideal aperture slightly smaller than the cryptospiral amphideal fovea, spacious and heavily cuticularised buccal cavity with large dorsal tooth and right subventral tooth situated anteriorly relative to left subventral tooth, slender spicules 4.4 cloacal body diameters long, and gubernaculum 1.2 cloacal body diameters long with laterally curved distal end and swollen proximal end. Bolbolaimus tongaensis n. sp. is characterised by annulated cuticle with longitudinal bars, oval amphideal aperture and cryptocircular amphideal fovea situated between cephalic setae and only partially surrounded by cuticle annulations, and short spicules cuticularised along dorsal edge and at proximal end and with swollen portion near proximal end. Maragnopsia n. gen. is characterised by a minute, non-cuticularised mouth cavity without teeth, an elongated posterior pharyngeal bulb more than twice as long as it is wide, a single outstretched testis, and a conico cylindrical tail 13-16 anal body diameters long. A list of all 83 valid Microlaimus species is provided. The present study provides the first microlaimid species records from deep-sea habitats (> 200 m depth) in the Southwest Pacific and Ross Sea. The presence of M. korari n. sp. on both the continental slope of New Zealand and Ross Sea abyssal plain suggests that this species has a wide geographical and depth distribution. However, molecular analyses will be required to confirm the identity of these two geographically disparate populations. PMID- 27396005 TI - Macrozoque hoplandrioides (Coleoptera: Staphylinidae: Aleocharinae), a new genus and species of false Lomechusini from Mexico. AB - Macrozoque hoplandrioides n. gen. and n. sp. (Coleoptera: Staphylinidae: Aleocharinae), is described based on specimens recently collected from the Chimalapas forest in Mexico. The systematic position of Macrozoque is discussed and is proviosionally placed in the false Lomechusini clade. A distribution map, keys and illustrations are provided. PMID- 27396006 TI - A pictorial key to the sections, groups, and species of the Aedes (Diceromyia) in the Afrotropical Region (Diptera: Culicidae). AB - Nine species of the subgenus Diceromyia Theobald of genus Aedes Meigen in the Afrotropical Region are treated in a pictorial key based on diagnostic morphological features. Images of the diagnostic morphological structures of the adult head, thorax, abdomen, leg and wing are included. The medical importance of the Furcifer Group species in Africa was briefly reviewed. PMID- 27396007 TI - New species and records of Anacroneuria (Plecoptera: Perlidae) from the northeastern semi-arid region of Brazil. AB - The genus Anacroneuria is widely distributed in the Neotropical Region. There are about 80 species listed from Brazil, five of which are recorded from the northeastern semi-arid region of Brazil, an area characterized by irregular and low precipitation. Examination of adult Anacroneuria material from this including areas of Caatinga desert vegetation and Atlantic forest revealed two new species records, A. debilis (Pictet) and A. terere Righi-Cavallaro & Lecci. Additionally, two new species, A. calori n. sp. and A. singela n. sp., are described from this material. These new records and new species reflect a major effort to document the biodiversity of the aquatic insects of the northeastern semi-arid region of Brazil by the Research Program in Semi-arid Biodiversity. PMID- 27396008 TI - Neostasina gen. nov., a new genus of huntsman spiders from the Neotropical region (Araneae, Sparassidae, Sparianthinae). AB - Neostasina gen. nov. is proposed to include the type species, Neostasina macleayi (Bryant, 1940) comb. nov., and four other described species: N. lucasi (Bryant, 1940) comb. nov. and N. saetosa (Bryant, 1948) comb. nov., transferred from Stasina Simon, 1877, N. bicolor (Banks, 1914) comb. nov., from Olios Walckenaer, 1837, and N. antiguensis (Bryant, 1923) comb. nov., from Pseudosparianthis Simon, 1887. Stasina portoricensis Petrunkevitch, 1930 and Olios darlingtoni Bryant, 1942 are considered junior synonyms of N. bicolor comb. nov. All species are redescribed and illustrated. Twenty-two new species are described, namely: N. baoruco sp. nov. (?), N. bermudezi sp. nov. (?, ?) and N. cachote sp. nov. (?) from the Dominican Republic, N. bryantae sp. nov. (?, ?), N. granpiedra sp. nov. (?, ?), N. iberia sp. nov. (?, ?), N. montegordo sp. nov. (?), N. siempreverde sp. nov. (?) and N. turquino sp. nov. (?) from Cuba, N. croix sp. nov. (?) from the Island of St. Croix and N. virginensis sp. nov. (?) from the Island of St. John, both U.S. Virgin Islands, N. guanaboa sp. nov. (?), N. gunboat sp. nov. (?), N. jamaicana sp. nov. (?), N. liguanea sp. nov. (?, ?), N. lucea sp. nov. (?), N. mammee sp. nov. (?, ?), and N. maroon sp. nov. (?, ?) from Jamaica, N. ouali sp. nov. (?, ?) from Nevis Island, N. amalie sp. nov. (?, ?) from U.S. (St. John and St. Thomas Islands) and British Virgin Islands (Peter Island and Sandy Cay), and N. taino sp. nov. (?, ?) from Puerto Rico and Dominican Republic. An identification key and distribution maps are provided for all known species. PMID- 27396009 TI - One new species and one newly recorded species of Cyllodes Erichson from China (Coleoptera: Nitidulidae: Nitidulinae). AB - One new species, Cyllodes quinquemaculatus Liu, Yang & Huang, sp. nov., one newly recorded species, Cyllodes accentus Kirejtshuk, 1985, from China and one previously known species, Cyllodes bifascies (Walker, 1859), are described. Photos of their habitus, antenna, mouthparts, and genitalia are provided. A species checklist of Cyllodes from China is presented. PMID- 27396010 TI - Review of the genus Apterolarnaca Gorochov (Orthoptera: Gryllacrididae) with proposal of a new synonym and description two new species. AB - Apterolarnaca ovala Bian & Shi, 2015 is proposed as a synonym of Apotrechus truncatolobus Li & Liu, 2015 and transfers the species to the genus Apterolarnaca Gorochov, 2004. Meanwhile, based on the collection of the Museum of Hebei University, two new Chinese species of Apterolarnaca are described, Apterolarnaca nigrifrontis Bian & Shi sp. nov. and Apterolarnaca quadrimaculata Bian & Shi sp. nov.. PMID- 27396011 TI - A review of the Japanese species of the genus Scardia Treitschke (Lepidoptera, Tineidae), with description of a new species. AB - Taxonomy of the Japanese species of the genus Scardia is reviewed, and a new species, namely Scardia fusca sp. nov., is described based on the adult morphology. PMID- 27396012 TI - Description of a new Kempnyia Klapalek from Brazil (Plecoptera: Perlidae) with life stages associated using DNA barcodes. AB - Kempnyia couriae sp. nov. is described from specimens (male, female, and nymphs) collected in Rio de Janeiro State, southeastern Brazil. This species is distinguished from its congeners by the male penial armature, having an elongate gonopore, surpassing the hooks, hooks with penial apex forming a globular membranous structure, and by ventrally curved hooks. Females and a nymph were associated with males using DNA barcoding. PMID- 27396013 TI - A new species of anguilliform catfish (Actinopterygii: Siluriformes: Bagridae) from Bangladesh and northeastern India. AB - We describe Olyra praestigiosa, a new anguilliform bagrid catfish, from the Brahmaputra River drainage in Bangladesh and northeastern India. The new species differs from congeners in having the following unique combination of characters: interorbital distance 30-37% HL; body depth at anus 6-9% SL; length of adipose fin base 99-16% SL; adipose fin separate from upper principal caudal-fin rays; post-adipose distance 15-18% SL; 17-22 anal-fin rays; caudal peduncle length 14 19% SL; and caudal peduncle depth 6-8% SL. PMID- 27396014 TI - The Scirtothrips perseae species-group (Thysanoptera), with one new species from avocado, Persea americana. AB - Following recent molecular studies on avocado thrips, a new species is described from Costa Rica, Ecuador, and Colombia from the young leaves of avocado, Persea americana. Scirtothrips hansoni sp.n. is closely related to the Californian pest, S. perseae, and also to S. astrictus from Costa Rica that remains known from a single female. An illustrated key to these three species is provided. PMID- 27396015 TI - Two new species of Cossinae (Lepidoptera: Cossidae) from Sindh Province of Pakistan. AB - The Cossidae fauna of Pakistan is still poorly studied, with only a few species reported: Eremocossus foedus (Swinhoe, 1884), Aholcocerus ronkayorum Yakovlev, 2006, Cossulus griseatellus Yakovlev, 2006 and Phragmataecia gurkoi Yakovlev, 2007. The carpenter moths of Zeuzera Latreille, 1804 (Zeuzera sp. and Z. multistrigata Moore, 1881) have been reported in pest management publications from Pakistan (Mushtaque & Baloch 1981; Gul & Wali-ur-Rehman 1999; Viqar et al. 2005). The distribution of known cossid species of Pakistan is treated by Yakovlev (2011) without indicating specific localities. Mushtaque and Baloch (1981) report Z. multistrigata caterpillars feeding on the roots of Cannabis sativa L. (Cannabidaceae), which needs to be confirmed. Otherwise Zeuzera species have been observed only feeding on woody plants (Yakovlev 2012). PMID- 27396016 TI - A new species of the leafhopper genus Matsumuratettix Metcalf (Hemiptera: Cicadellidae: Deltocephalinae: Deltocephalini) from Thailand. AB - Matsumura (1914) established Epitettix with the type species E. hiroglyphicus Matsumura, 1914 from Taiwan. Metcalf (1952) proposed the new name Matsumuratettix for Epitettix Matsumura, which was preoccupied by Epitettix Hancock, 1907. Dash & Viraktamath (1995) synonymised Pruthiorosius Ghauri with Matsumuratettix Metcalf. Currently, Matsumuratettix comprises a single species, M. hiroglyphicus (Matsumura, 1914). The genus is easily distinguished from other Old World Deltocephalini by the aedeagal shaft being strongly laterally compressed over the distal two-thirds and with asymmetrical distal spines. In this paper, a new species is described from Thailand and a key to distinguish the two known species is provided. PMID- 27396017 TI - Posttraumatic Stress Disorder and Stressful Life Events Among Rural Women With HIV Disease. AB - Posttraumatic stress disorder (PTSD) and stressful life events are frequent and distressing problems for women living with HIV (WLWH). Studies have independently focused on the impact of these problems, but little work has examined the relationship between PTSD and stressful life events. Our cross-sectional study examined relationships between PTSD and recent stressful life events in WLWH. A sample of 60 women recruited through HIV community agencies in southeastern North Carolina completed the Stressful Life Events Questionnaire and the PTSD Checklist Civilian Version (PCL-C). PTSD prevalence was high (43.2%). Two-thirds (66%) reported three or more recent life stressors. Women who experienced a higher number of recent life stressors scored higher on the PCL-C than those with fewer life stressors (p < .001). Recent stressful life events may accelerate PTSD symptoms. Findings underscore the importance of addressing mental health issues in HIV treatment settings. Implications for nursing practice are provided. PMID- 27396018 TI - Potential therapeutic value of miR-425-5p in metastatic colorectal cancer. PMID- 27396020 TI - Renal guidelines a fluid resource. PMID- 27396019 TI - Resource-dependent antagonistic coevolution leads to a new paradox of enrichment. AB - The classical, ecological, paradox of enrichment describes a phenomenon that resource enrichment destabilizes predator-prey systems by exacerbating population oscillations. Here we suggest a new, evolutionary, paradox of enrichment. Resource enrichment can lead to more asymmetrical predator-prey coevolution (i.e., extremely high levels of prey defenses against predators) that decreases predator abundances and increases predator extinction risk. A major reason for this is that high resource availability can reduce fitness costs associated with prey defenses. In our experiments with a bacterium and its lytic phage, nutrient balanced resource enrichment led to patterns in population demography and coevolutionary dynamics consistent with this coevolution-based paradox of enrichment; in particular, phage population extinction events were observed under nutrient-rich, not nutrient-poor, conditions. Consistent with ecological studies, carbon-biased resource enrichment (with carbon availability disproportionately increased relative to other nutrients) did not destabilize dynamics, and the asymmetry of coevolution was not altered in this context. Our work highlights the importance of integrating ecological and evolutionary thinking for studies of the consequences of nutrient pollution and other types of environmental changes. PMID- 27396021 TI - More on anesthesia-free dental cleanings. PMID- 27396023 TI - Incentive to improve dog behavior. PMID- 27396022 TI - Urging AVMA BOD support of the Equality Act of 2015. PMID- 27396024 TI - The importance of puppy socialization. PMID- 27396026 TI - The harm of recruiting in veterinary medicine. PMID- 27396025 TI - Exposure of dogs to electronic cigarettes. PMID- 27396027 TI - The Authors Respond. PMID- 27396028 TI - New NCCN Guidelines Include Evidence Blocks to Illustrate Value in Breast, Colon, Kidney, and Rectal Cancers. PMID- 27396029 TI - NCCN Publishes New Clinical Practice Guidelines for Vulvar Cancer. PMID- 27396031 TI - Nurses must embrace research. PMID- 27396030 TI - NCCN Awarded $2 Million in Research Funding from Infinity Pharmaceuticals to Study Duvelisib in Hematologic Malignancies. PMID- 27396032 TI - Not all nurses supported Butler's behaviour. PMID- 27396034 TI - Who are the real heroes? PMID- 27396033 TI - Havill's letter misleading. PMID- 27396035 TI - Appalled by new master's degree. PMID- 27396037 TI - Equipping union members. PMID- 27396036 TI - [Not Available]. PMID- 27396038 TI - Studying cyberbullying. PMID- 27396039 TI - Faith nurses' conference. PMID- 27396040 TI - Grateful for research support. PMID- 27396041 TI - The kaiwhakahaere comments. PMID- 27396042 TI - Health strategy doesn't empower nursing. PMID- 27396043 TI - Workforce messages target 'vulnerable areas'. PMID- 27396044 TI - New Maori name for NZNO. PMID- 27396045 TI - Improving access for whanau to tupapaku. PMID- 27396046 TI - Nuku takes claim to UN. PMID- 27396047 TI - DHB's mask stance unchanged. PMID- 27396048 TI - Aged-care workforce to be surveyed. PMID- 27396050 TI - 'Toughen up' attitude behind bullying. PMID- 27396049 TI - Nurses and midwives have key role in child protection. PMID- 27396051 TI - No equal pay settlement yet. PMID- 27396052 TI - Caring for the dying mind. PMID- 27396053 TI - Former nurse heads DHB. PMID- 27396054 TI - Helping children participate in health decisions affecting them. PMID- 27396055 TI - Hospital midwives' work becoming more complex. PMID- 27396056 TI - Involving parents in the care of neonates. PMID- 27396057 TI - Using advanced neonatal skills. PMID- 27396059 TI - Reducing neonatal readmission rates. PMID- 27396058 TI - Transporting babies in an emergency. PMID- 27396060 TI - Speaking for neonates and their families. PMID- 27396061 TI - One nurse's climate change journey. PMID- 27396062 TI - Providing neonatal education overseas. PMID- 27396063 TI - Bonded nurses share their experiences. PMID- 27396064 TI - Moving from students to competent RNs. PMID- 27396065 TI - Early detection of heart defects can save lives. PMID- 27396066 TI - A career devoted to neonates. PMID- 27396067 TI - Why stand for election as an NZNO board member? PMID- 27396068 TI - Debating euthanasia. PMID- 27396069 TI - Court nursing: Facing 'vicarious trauma'. PMID- 27396070 TI - Intensive care: Using virtual consultations. PMID- 27396071 TI - Rural general practice: Expanding roles for nurses. PMID- 27396072 TI - Nurse education: Links to improved care. PMID- 27396073 TI - Neonatal nursing: Palliative care guidelines. PMID- 27396074 TI - Improving employee protections. PMID- 27396075 TI - DHBs: Two long-standing delegates take their leave. PMID- 27396076 TI - New facility opens in Kaikoura. PMID- 27396077 TI - NZNO supports protest over food at Southern DHB. PMID- 27396078 TI - Aged care: National interRAI service to be established. PMID- 27396079 TI - Primary care: Prison nurse staffing levels must be discussed. PMID- 27396080 TI - "Nursing directors have a tough but crucial job". PMID- 27396081 TI - Trusts struggling to stick to agency caps. PMID- 27396082 TI - Nursing leaders welcome CNO for England's new framework. PMID- 27396083 TI - Nurses told to engage more with technology. PMID- 27396084 TI - Meeting nurses' needs cited as key to reducing staff turnover. PMID- 27396085 TI - Regulator chief to support UK's future nurse leadership. PMID- 27396086 TI - HEE reveals plans to improve nurse education and training. PMID- 27396087 TI - Fall in demand for health visitor training places. PMID- 27396088 TI - HEE looks at alternative methods of student nurse mentorship. PMID- 27396089 TI - More staff key to reducing neonatal death. PMID- 27396090 TI - Charity nurses warn of 'postcode lottery' in specialist paediatrics. PMID- 27396091 TI - Pilot aims to boost training in care homes. PMID- 27396092 TI - "We need a community of care in place of EU neoliberalism". PMID- 27396093 TI - "The nursing associate role will belittle the value of bedside care". PMID- 27396094 TI - "Small changes can have a large impact on hospital discharge". PMID- 27396095 TI - Service aids prisoners with sleep apnoea. PMID- 27396097 TI - Transparency in drug industry relationships. PMID- 27396096 TI - Meeting the needs of four generations of nurses. AB - Every year increasing numbers of nurses and midwives leave the NHS. In the current climate of staff shortages it is crucial to understand why this is happening and try to resolve the problem; in Birmingham we have taken steps to do this. This article explores the different workforce generations, along with strategies that could enhance nursing and midwifery careers, ensuring they meet the needs of all generations, thereby encouraging practitioners to stay in their profession for longer. PMID- 27396098 TI - Developing a sleep apnoea clinic for prisoners. AB - People in prison may experience barriers in accessing health services. By exploring some of these barriers and how they have been overcome, this article describes how prisoners were made aware of obstructive sleep apnoea and the associated risks, and how a clinic was set up in a prison healthcare centre. It shows how access to a community service was made available to the prisoners, and details how the service was set up, how it operates and what the outcomes achieved. PMID- 27396099 TI - Care of patients with permanent tracheostomy. AB - The third article in our series on tracheostomy care discusses the care of patients with a permanent tracheostomy. While these patients make up a small proportion of all patients who have a tracheostomy inserted, they have complex needs. This means they require practitioners in both acute and community settings, who have time, support and competent tracheostomy-care skills, to achieve a successful discharge and ongoing management of their tracheostomy. PMID- 27396100 TI - Osteoporosis: the clinical nurse specialist role. PMID- 27396101 TI - 60 seconds with Jo Fearn. PMID- 27396102 TI - Taking flight from nursing. PMID- 27396103 TI - [Effect of seasonal high temperature and drought on carbon flux of bamboo forest ecosystem in subtropical region]. AB - The carbon flux of subtropical bamboo forest ecosystem was continuously measured using eddy covariance technique in Anji County of Zhejiang Province, China. The monthly net ecosystem productivity (NEP), ecosystem respiration (Re) and gross ecosystem productivity (GEP) data from 2011 to 2013 were selected to analyze the impacts of seasonal high temperature and drought on the carbon flux of bamboo forest ecosystem. The results showed that there were big differences among annual NEP of bamboo forest from 2011 to 2013. Because of the asynchronization of precipitation and heat, the seasonal high temperature and drought in July and August of 2013 caused significant decline in NEP by 59.9% and 80.0% when compared with the same months in 2011. Correlation analysis of the NEP, Re, GEP and environmental factors suggested that the atmosphere temperatures were significantly correlated with Re and GEP in 2011 and 2013 (P<0.05). However, to air and soil moisture, Re and GEP had different responses, that was, GEP was more vulnerable by the decrease of the soil moisture compared with Re. Besides, the raising of saturation vapour pressure promoted the Re modestly but inhibited the GEP, which was supposed to be the main reason for NEP decrease of bamboo forest ecosystem in Anji, from July to August in 2013. PMID- 27396104 TI - [Dynamics of sap flow density in stems of typical desert shrub Calligonum mongolicum and its responses to environmental variables]. AB - Independent measurements of stem sap flow in stems of Calligonum mongolicum and environmental variables using commercial sap flow gauges and a micrometeorological monitoring system, respectively, were made to simulate the variation of sap flow density in the middle range of Hexi Corridor, Northwest China during June to September, 2014. The results showed that the diurnal process of sap flow density in C. mongolicum showed a broad unimodal change, and the maximum sap flow density reached about 30 minutes after the maximum of photosynthetically active radiation (PAR) , while about 120 minutes before the maximum of temperature and vapor pressure deficit (VPD). During the studying period, sap flow density closely related with atmosphere evapor-transpiration demand, and mainly affected by PAR, temperature and VPD. The model was developed which directly linked the sap flow density with climatic variables, and good correlation between measured and simulated sap flow density was observed in different climate conditions. The accuracy of simulation was significantly improved if the time-lag effect was taken into consideration, while this model underestimated low and nighttime sap flow densities, which was probably caused by plant physiological characteristics. PMID- 27396105 TI - [Response of Picea purpurea and Abies faxoniana tree rings at different slope aspects to rapid warming in western Sichuan, China]. AB - By using an empirical 'signal-free' standardization approach, we constructed four Picea purpurea and Abies faxoniana tree-ring chronologies at southeast and northwest slope aspects of Erdaohai and east slope aspect of Zharisi, Songpan, west Sichuan, China. The response analysis and multivariate analysis of variance between tree rings and climatic variables were conducted to explore the divergent responses of tree growth at different slope aspects to the recent warming climate. Results showed that tree growth of P. purpurea at east slope aspect was obviously accelerated (0.011 a-1) since rapid warming in 1980, whereas those at northwest slope aspect was significantly reduced (-0.006 a-1). Tree growth of P. purpurea at southeast slope aspect and A. faxoniana at northwest slope aspect decreased in significantly. With the rapid warming, growth-climate relationships of P. purpurea and A. faxoniana at different slope aspects changed significantly. After rapid warming in 1980, the promoting effects of growing season temperature (GST) on P. purpurea growth at east slope increased significantly, while the inhibitory effects of GST on its growth at southeast and northwest slopes also increased significantly. However, the effects of GST on A. faxoniana growth at northwest slope did not change significantly before and after rapid warming. The effects of precipitation in May (PM) on P. purpurea growth at east slope was changed from inhibition before rapid warming to significant promotion after rapid warming, while the inhibitory effects of PM on P. purpurea growth at southeast and northwest slopes increased significantly. For A. faioniana at northwest slope, however, it did not change obviously before and after rapid warming. The response analysis between tree growth and the Palmer drought severity index (PDSI) showed that soil moisture variations at different slope aspects were an important reason of tree-ring growth response difference since rapid warming. In addition, the results of multivariate analysis of variance indicated that the combined effects of slope aspect, temperature and precipitation factors were the most important limited factors for tree growth variability in western Sichuan. Therefore, we should consider the combined effects of temperature, precipitation and different slope aspects when simulating and predicting tree-growth response to the recent climate warming trend. PMID- 27396106 TI - [C, N, P stoichiometric characteristics of tree, shrub, herb leaves and litter in forest community of Shaanxi Province, China]. AB - A total of 121 sampling sites were selected to study the C, N, P stoichiometric characteristics among the leaves of tree, shrub, herb and the litter of the majority forest community of Shaanxi Province, China. We also studied their relationships with geographical factors. The results showed that C, N concentrations were highest in tree leaf, P concentration was highest in herb leaf, and the C, N, P concentrations were lowest in litter. Leaf C: N: P ratios of tree, shrub, herb leaves and litter were 439.4:14.2:1, 599.2:13.5:1, 416.5:13.3:1, 504.8:15.5:1, respectively. The N:P ratios of tree, shrub and herb leaves were not significantly different, but they were all significantly higher than that of litter layer, indicating N:P ratio of different living life forms' leaves was stable. Compared with N, C and P had better relationships in each layer, and the relationships of leaf C, N, P stoichiometry between tree and herb leaves were better than those between tree and shrub leaves. The correlations of C, N, P stoichiometry between litter and the tree or herb leaves were highly significantly positive, and the correlations of P stoichiometry between litter and shrub leaves were highly significantly positive. Shrub leaf N, P concentration increased with the increasing latitude, and herb leaf N, P concentrations decreased with the increasing longitude. Compared with the longitude and latitude, the effect of altitude was smaller, and only tree leaf N:P decreased with the increasing latitude. Multivariate linear regression analysis results showed that the influence of geographical factors on herb leaf was longitude > latitude > altitude, while was latitude > longitude > altitude for tree, shrub leaves and litter. PMID- 27396107 TI - [Effects of elevated O3 on leaf litter decomposition and nutrient release of Quercus mongolica in city]. AB - The leaf litters of 10-year-old Quercus mongolica were put in nylon bags and exposed to elevated 03 level (120 nmol . mol-1) with the control of 40 nmol . mol 1 in open top chambers (OTCs) for 150 days to test the effect of high O3 on the litter decomposition. The results showed that no significant difference was observed in residual mass between elevated O3 treatment and the control. Elevated 03 inhibited the release of C and K during the decomposition, the residual rate of K under elevated O3 treatment (23.9%) was significantly higher than that of the control (17.1%) after 150-day decomposition. Compared with the control, N mineralization and lignin degradation in elevated O3 treatment were inhibited during early period of decomposition (0-60 d), but were promoted in later period (90-150 d). The changes of lignin/N showed no significant difference between elevated O3 treatment and the control during the decomposition. Elevated O3 generally promoted the release of P in leaf litter of Q. mongolica during the decomposition. C/P ratio was higher under elevated 03 than that under control. Significant positive correlation was shown between residual dry mass of leaf litters and the residual rate of C, N, K, C/N ratio during decomposition. Elevated 03 might play an important role in the nutrient cycle of forest ecosystem in high-O3 pollution area. PMID- 27396108 TI - [Tree uprooting of coniferous-broad leaved Korean pine mixed forest in Lesser Khingan Mountains, China]. AB - The morphological parameters, root wad indexes and site conditions of 127 uprooting trees from 76 plots (20 mx20 m) in Lesser Khingan coniferous-broad leaved Korean pine mixed forest were measured. Then the influencing factors of uprooting differences and the relationship between uprooting trees and disturbed soil were analyzed. Results showed that the number of uprooting trees varied significantly among species. Abies nephrolepis suffered the most serious uprooting damage, then Pinus koraiensis, and Ulmus spp. the least. Deciduous species had a stronger uprooting-resistant capacity than broad-leaved species. With the increase of tree DBH and height, tree' s uprooting resistance declined rapidly first and then was gradually enhanced, and finally reached the minimum at diameter class of 20 cm and height class of 14 m, respectively. The smaller the taper degree and projected area of crown were, the stronger the uprooting resistance was. Uprooting rate was negatively correlated with stand density. Trees lying in wet ground, flat terrain, medium low altitude area and windward slope had a greater risk of uprooting. There were significant positive correlation between the depth, area and volume of disturbed soil and the DBH, height, volume of uprooting trees. PMID- 27396109 TI - [Spatial pattern analysis and associations of Quercus aquifolioides population at different growth stages in Southeast Tibet, China]. AB - This article analyzed the spatial pattern and its correlation of Quercus aquifolioides, Southeast Tibet at different growing stages by using Ripley' s L function in the method of point pattern, analysis. The results showed the diameter structure of Q. aquifolioides population in Southeast Tibet followed a 'single peak' shape and the saplings and medium trees predominated in number in the whole population. The population had a high regeneration rate and was of increase type. In the growth process of Q. aquifolioides from saplings to large trees, saplings and medium trees showed aggregation distribution at.small scale, while large trees showed basically random distribution at whole scale. There was significant correlation between saplings with medium or large trees at small scale, however, there was no correlation between medium and large trees. In the growth process of Q. aquifolioides population from saplings, medium trees to large trees, its spatial pattern developed from aggregative distribution to random distribution. The natural regeneration of Q. aquifolioides population was affected not only by interspecific competition, but also by intraspecific competition. In the similar natural environment, the most important factors affecting the spatial pattern of Q. aquifoioides population were its own biological and ecological characteristics. PMID- 27396110 TI - [Seasonal dynamics of quantitative and morphological traits of poplar fine roots and their differences between successive rotation plantations]. AB - Based on the fine root samples of the first and second generations of poplar (Populus x euramericana ' Neva'), this study examined the response of quantitative and morphological traits of fine roots of different orders and the difference between generations. The results showed that, the quantitative traits of fine roots, such as root length, root surface area and root biomass, presented obvious seasonal variation, and the fine root traits had obvious difference among root orders. The quantitative traits of lower-order fine roots showed significant seasonal difference, and the fine root biomass increased in the growing season and then decreased significantly. The specific root length (SRL) of higher-order roots also showed significant change with season, while the root length density (RLD) and root tissue density (RTD) changed a little. The successive rotation resulted in the significant increase of root length, root biomass, SRL and RLD of 1-2 orders in the growing season. The quantitative traits of first order root significantly positively correlated with soil temperature and moisture, and significantly negatively correlated with the soil organic matter and soil available nitrogen content. However, the quantitative traits of second order root only showed significant correlation with soil nutrient content. The seasonal dynamics of poplar fine roots and the difference between successive rotation plantations implied carbon investment change of poplar to roots. Soil nutrient deficiency induced more carbon investment into roots, and this carbon allocation pattern might affect the aboveground productivity of poplar plantation. PMID- 27396111 TI - [Spatial distribution paittern of Populus euphratica and P. pruinosa1 clonal ramets in Ta.rim River Basin, China]. AB - Spatial distribution pattern of Populus euphratica and P. pruinosa clonal ramets at three sites was studied, including natural mixed forest of P. euphratica and P. pruinosa in Awati County located in the downstream of Yarkant River, natural P. pruinosa forest in Group 16 of Nongyishi in the Tarim River upstream area, and natural P. euphratica forest in Luntai County located in the middle reach of the Tarim River. The clonal ramets of the three sites showed a cluster distribution pattern at eight sampling scales, i.e., 5 mx5 m, 5 mx10 m, 5 mx15 m, 10 mx10 m, 10 mx15 m, 15 mx15 m, 15 mx20 m, and 20 mX20 m. This pattern revealed that the cluster distribution was a basic property in the spatial distribution pattern of P. euphratica and P. pruinosa populations. At 5 mx5 m scale, negative binomial parameter was minimum, while Cassie index, patchiness inex and aggregation strength were maximum for the two ramet populations at the three sites. PMID- 27396112 TI - [Parameter sensitivity of simulating net primary productivity of Larix olgensis forest based on BIOME-BGC model]. AB - Model based on vegetation ecophysiological process contains many parameters, and reasonable parameter values will greatly improve simulation ability. Sensitivity analysis, as an important method to screen out the sensitive parameters, can comprehensively analyze how model parameters affect the simulation results. In this paper, we conducted parameter sensitivity analysis of BIOME-BGC model with a case study of simulating net primary productivity (NPP) of Larix olgensis forest in Wangqing, Jilin Province. First, with the contrastive analysis between field measurement data and the simulation results, we tested the BIOME-BGC model' s capability of simulating the NPP of L. olgensis forest. Then, Morris and EFAST sensitivity methods were used to screen the sensitive parameters that had strong influence on NPP. On this basis, we also quantitatively estimated the sensitivity of the screened parameters, and calculated the global, the first-order and the second-order sensitivity indices. The results showed that the BIOME-BGC model could well simulate the NPP of L. olgensis forest in the sample plot. The Morris sensitivity method provided a reliable parameter sensitivity analysis result under the condition of a relatively small sample size. The EFAST sensitivity method could quantitatively measure the impact of simulation result of a single parameter as well as the interaction between the parameters in BIOME-BGC model. The influential sensitive parameters for L. olgensis forest NPP were new stem carbon to new leaf carbon allocation and leaf carbon to nitrogen ratio, the effect of their interaction was significantly greater than the other parameter' teraction effect. PMID- 27396113 TI - [Response of phenophase to meteorological conditions and flowering forecast model on Amygdalus communis in Shache County, Xinjiang, China]. AB - Based on the phenophase data of Amygdalus communis and homochronous meteorological observation data at agrometeorological experimental station of Shache County during 2008-2013, the change characteristics of phenological period of A. communis and the effects of temperature and sunshine duration on them were analyzed. The results showed that before flowering, positive correlations existed among the first day of phenological phases, and after flowering, the correlations among the first day of phenological phases were mostly less. A significant positive correlation was observed between earlier bud flower swelling and the days of dormant period. and growth period, and a significant negative correlation existed between later bud flower swelling and the days of dormant period and growth period. Before fruit maturation, there was negative correlation between temperature and the interval days of phenological period, and after fruit maturation, the correlations were mostly positive. But the correlation between sunshine duration and the interval days of phenological period was positive before and after fruit maturation. The interval days from fruit maturation to the beginning date of leaf colour change had evident response to the average maximum temperature, and the interval days from the emergence of inflorescence to the ending data of flowering, and from the beginning date of leaf colour change to the ending date of leaf fall, had obvious response to sunshine duration. When the dormant period exceeded 30 days and the average daily temperature met the rang from -3.0 to -7.5 degrees C, A. communis would get into the flower swelling period after another 17-28 d. There were one-to-one correspondences between flower swelling, the beginning date of flowering, the beginning date of leaf colour change, the ending date of leaf fall, and the first pentad average temperature greater than or equal to 4 degrees C and pentad average maximum temperature greater than or equal to 12 degrees C, pentad average temperature greater than or equal to 14 degrees C and pentad average maximum temperature greater than or equal to 22 degrees C in spring, the first pentad temperature less than or equal to 10 degrees C and pentad average maximum temperature less than or equal to 18 degrees C in autumn the first pentad average temperature less than or equal to 1.9 degrees C in winter, respectively. By using partial least squares regression analysis, the first day of flowering forecast model of A. communis was established with good prediction. PMID- 27396114 TI - [Automated mapping of urban forests' disturbance and recovery in Nanjing, China]. AB - Using Landsat TM/ETM dense time series observations spanning from 1987 to 2011, taking Laoshan forest farm and Purple Mountain as the research objects, the landsat ecosystem disturbance adaptive processing system (Ledaps) algorithm was used to generate surface reflectance datasets, which were fed to the vegetation change tracker model (VCT) model to derive urban forest disturbance and recovery products over Nanjing, followed by an intensive validation of the products. The results showed that there was a relatively high spatial agreement for forest disturbance products mapped by VCT, ranging from 65.4% to 95.0%. There was an apparent fluctuating forest disturbance and recovery rate over time, and the change trend of forest disturbance occurring at the two sites was roughly similar, but forest recovery was obviously different. Forest coverage in Purple Mountain was less than that in Laoshan forest farm, but the forest disturbance and recovery rates in Laoshan forest farm were larger than those in Purple Mountain. PMID- 27396115 TI - [Nitrogen fixation potential of biological soil crusts in Heidaigou open coal mine, Inner Mongolia, China]. AB - Nitrogen limitation is common in terrestrial ecosystems, and it is particularly severe in damaged ecosystems in arid regions. Biological soil crusts (BSCs) , as a crucial component of recovered vegetation, play a vital role in nitrogen fixation during the ecological restoration processes of damaged ecosystems in arid and semi-arid regions. In this study, two dominant types of BSCs (i.e., cyanobacterial-algal crusts and moss crusts) that are widely distributed in the re-vegetated area of Heidaigou open pit coal mine were investigated. Samples were collected in the field and their nitrogenase activities (NA) were measured in the laboratory. The responses of NA to different hydro-thermal factors and the relationships between NA and herbs in addition to crust coverage were analyzed. The results indicated that BSCs under reconstructed vegetation at different succession stages, abandoned land and natural vegetation showed values of NA ranging from 9 to 150 umol C2H4 . m-2 . h-1, and the NA value of algae crust (77 umol C2H4 . m-2 . h-1) was markedly higher than that of moss crust (17 umol C2H4 . m-2 . h-1). In the re-vegetated area, cyanobacterial-algal crust and moss crust under shrub-herb had higher NA values than those of crusts under arbor-shrnb and arbor-shrub-herb. The relationship between NA of the two BSCs and soil relative water content (10% - 100%) as well as culture temperature (5-45 degrees C) were of quadratic function. With elevated water content and cultural temperature, the NA values increased at the initial stage and then decreased, and reached the maximum value at 25 degrees C of cultural temperature and 60% or 80% of relative water content. The NA of cyanobacterial-algal crust had a significant quadratic function with herb coverage, as NA declined when herb coverage was higher than 20%. A significant negative correlation was observed between the NA of moss crusts and herb coverage. The NA values of the two types of BSCs had a significant positive correlation with crust coverage, since the NA was enhanced when the crust coverage was increased. We concluded that the different NA of the two BSCs in the re-vegetated area of Heidaigou open pit coal mine were caused by the composition of cryptograms. In addition, the differences of hydrothermal conditions and the composition of herb or crust coverage at different succession stages were also the contribution factors. Therefore, BSC construction and nitrogen fixation in re-vegetated areas is an important symbol for sustainable development in ecosystems. PMID- 27396116 TI - [Effects of supplemental irrigation by monitoring soil moisture on the'water nitrogen utilization of wheat and soil NO3(-)-N leaching]. AB - Field experiments were conducted during 2012-2014 wheat growing seasons. With no irrigation in the whole stage (WO) treatment as control, three supplemental irrigation treatments were designed based on average relative soil moisture contents at 0-140-cm layer, at jointing and anthesis stages (65% for treatment W1 ; 70% for treatment W2; 75% for treatment W3; respectively), to examine effects of supplemental irrigation on nitrogen accumulation and translocation, grain yield, water use efficiency, and soil nitrate nitrogen leaching in wheat field., Soil water consumption amount, the percentage of soil water consumption and water irrigation to total water consumption in W2 were higher, and soil water consumption of W2 in 100-140 cm soil layer was also higher. The nitrogen accumulation before anthesis and after anthesis were presented as W2, W3>W1>W0, the nitrogen accumulation in vegetative organs at maturity as W3>W2>Wl>W0, and the nitrogen translocation from vegetative organs to grain and the nitrogen accumulation in grain at maturity as W2> W3>W1>W0. At maturity, soil NO3(-)-N content in 0-60 cm soil layer was presented. as W0>W1>W2>W3, that in 80-140 cm soil layer was significantly higher in W3 than in the other treatments, and no significant difference was found in 140-200 cm soil layer among all treatments. W treatment obtained the highest grain yield, water use efficiency, nitrogen uptake efficiency and partial productivity of applied nitrogen. As far as grain yield, water use efficiency, nitrogen uptake efficiency and soil NO3(1)-N leaching were concerned, the W2 regime was the optimal irrigation treatment in this experiment. PMID- 27396117 TI - [Effects of increased planting density with reduced nitrogen fertilizer application on rice yield, N use efficiency and greenhouse gas emission in Northeast China]. AB - The traditional rice growing practice has to change to save resource and protect environment, and it' s necessary to develop new technology in rice cultivation. Therefore, a two-year field experiment of Japonica rice (Liaoxing 1) was conducted in Northeast China in 2012 and 2013 to investigate the integrated effects of dense planting with less basal nitrogen (N) and unchanged top-dressing N (IR) on rice yield, N use efficiency (NUE) and greenhouse gas emissions. Compared with traditional practice (CK), we increased the rice seedling density by 33.3% and reduced the basal N rate by 20%. The results showed that the average N agronomy efficiency and partial factor productivity were improved by 49.6% (P<0.05) and 20.4% (P<0.05), respectively, while the area and yield-scaled greenhouse gas emissions were reduced by 9.9% and 12.7% (P<0.05), respectively. Although IR cropping mode decreased panicle number and biomass production, it significantly enhanced rice seed setting rate and harvest index, resulting in an unchanged or even highei yield. NH4+-N and NO3(-)-N concentrations in rice rhizosphere soil were reduced, resulting in an increment of N recovery efficiency. Generally, proper dense planting with less basal N applicatior could be a good approach for the trade-off between rice yield, NUE and greenhouse gas emission. PMID- 27396118 TI - [Effects of cultural factors on yield of Linum usitatissimum (Tianya 9)]. AB - Cultural factors influencing high yield and good quality Linum usitatissimum (Tianya 9) were investigated. The correlations between these factors and its yield were analyzed. Path coefficient and principal component analysis were conducted, adopting uniform design of the 8 cultivating factors, i.e. planting density (X1), base nitrogen quantity (X2), base phosphorus quantity (X3), base potassium quantity (X4), foliar fertilizer (potassium dihydrogen phosphate, X5), foliar fertilizer (boron fertilizer, X6), growth regulator (multi-effect azole, X7) and growth duration irrigation amount (X8), aiming at exploring better cultivating plan of L. usitatissimum for Gansu Province. The results indicated that the factors influencing the yield of L. usitatissimum were X1, X7, X2, X3, X5 and X4 in a descending order. Simulation and optimization of the highest yield was further implemented. Frequency analysis showed that the cultivating factors resulting in yield higher than 173.58 kg . hm-2 were 4. 68 - 4. 92 kg . hm-2 (X1) , 11. 59 - 14. 75 kg . hm-2 (X2), 17.26- 21.95 kg . hm-2 (X3), 7.00-12.50 kg . hm 2 (X4) , 1.41-1.81 kg . hm-2 (X5) and 751.74- 954.04 g . hm-2 (X7). PMID- 27396119 TI - [Relationship between cellulose synthesis metabolism and lodging resistance in intercropping soybean at seedling stage]. AB - Physical characteristics of stem are closely relative to the crop lodging. Increase of stem strength is conducive to resolve the problem of lodging. Three soybean cultivars with different shade tolerance were planted under maize-soybean intercropping and soybean monocropping, respectively. Physiological and biochemical indices including cellulose, soluble sugar, sucrose, starch contents and enzyme activity were investigated to assess the snapping resistance and lodging resistance of the stems of soybean seedling, and snapping- and lodging resistance indices were calculated for further verification. Furthermore, relationship analyses between these factors and the lodging of inter-cropped soybean showed that the intercropping soybean lodged seriously, the snapping resistance, lodging resistance index, contents of cellulose, soluble sugar, sucrose, starch and activities of the related enzymes were significantly lower than monocropping soybean at seedling stage. The three soybean cultivars showed different phenotypes in intercropping condition. The snapping-resistant Nandou12 with strong shade-tolerant traits was the most lodging-resistant phenotype, and it also harbored high contents of cellulose, soluble sugar, sucrose, starch and active enzymes. The lodging resistance index, cellulose content of the stems of intercropped soybean seedling were significantly positively correlated with the snapping resistance, and were significantly negatively correlated with the actual lodging percentage. The activities of sucrose phosphate synthase (SPS) , sucrose synthase (SS) and neutral invertase (NI) were positively correlated with sucrose is content, but not the acid invertase (AI). The activities of SPS, NI and SS were positively correlated with cellulose content, but not Al. In a word, the high activities of SPS and SS in the soybean stem were the enzymatic basis to maintain relatively higher cellulose and sucrose content, which is conducive to improve the stem-sfrength and enhance the lodging resistance ability in intercropping condition. Effects of different light conditions on cellulose metabolic mechanism of soybean seedling stems, lodging resistant characteristics of soybean seedlings studied in the corn-soybean intercropping system provided a basis for screening more shade-tolerant soybean variety. PMID- 27396120 TI - [Effects of cold-shock on the growth and flower bud differentiation of tomato seedlings under high temperature stress]. AB - In order to explore the effects of cold-shock on the growth and flower bud differentiation of tomato seedlings under high temperature, tomato seedlings were subjected to cold-shock treat- ments every day with 10 degrees C for 10 minutes in. an artificial climate chamber. Tomato seedlings were treated with cold-shock at the first true leaf stage and the treatment lasted for 15 days. Tomato seed- lings without cold-shock were used as control. At the fourth true leaf period of tomato seedlings, five plants were randomly sampled and the growth characteristics and the ultrastructure changes of meso- phyll cell of tomato seedlings were examined. The flower bud differentiation process of tomato seed- lings was observed at the periods of the second, fourth and sixth true leaves respectively. Flowering and fruiting of tomato seedlings were also investigated after transplanting. The results showed that the stem diameter and health index of tomato seedlings with cold-shock were enhanced by 7.2% and 55.5% compared with seedlings without cold-shock. Mesophyll cells of the seedlings with cold-shock arranged loosely and various organelles such as chloroplasts and mitochondria were morphologically integrated, while chloroplasts and mitochondria of seedlings mesophyll cells without cold-shock swelled up and thylakoids vacuolized apparently. The flower bud differentiation process of seedlings with cold-shock could be advanced significantly at the early seedling stage compared with the control and the advancement was weakened with the seedling growing. Fruit set number and percentage on the first and second inflorescence of tomato plants transplanted by seedlings with cold-shock were enhanced significantly compared with those of the control. These results indicated that the injury of membrane structure of various organelles, especially chloroplast and mitochondria could be allevia- ted by cold-shock treatment under high temperature tress. Cold-shock treatment could not only im- prove the seedling growth under high temperature stress, but also advance the process of early flower bud differentiation and improve the fruit set. PMID- 27396121 TI - [Effects of interaction between vermicompost and probiotics on soil nronerty, yield and quality of tomato]. AB - In this study, we investigated the effects of two strains of probiotic bacteria (Bacillus megaterium BM and Bacillus amyloliquefaciens BA) combined with chemical fertilizers and vermicompost on the soil property, the yield and quality of tomato. The results showed that under the same nutrient level, vermicompost significantly increased the yield, soluble sugar and protein contents of fruit, the soil pH and available phosphorus when compared with chemical fertilizers. Vermicompost combined with probiotics not only increased the tomato yield, soluble sugar, protein and vitamin C contents, sugar/acid ratio of fruit, and reduced the organic acid and nitrate nitrogen contents of fruit, also increased the soil pH and nitrate nitrogen content, and reduced soil electric conductivity when compared with vermicompost treatment. This improved efficiency was better than that by chemical fertilizers combined with probiotics. For BA and BM applied with chemical fertilizers or vermicompost, both stains had no significant effect on tomato quality. When co-applied with vermicompost, BA and BM showed significant difference in tomato yield. High soil available phosphorus content was determined when BM was combined with chemical fertilizers, while high soil available potassium content was obtained when BA was combined with vermicompost. Our results suggested that probiotics and vermicompost could be used as alternatives of chemical fertilizers in tomato production and soil fertility improvement. PMID- 27396122 TI - [Effects of exogenous spermidine on mitochondrial function of tomato seedling roots under salinity-alkalinity stress]. AB - Two cultivars of tomato (Solanum lycopersicum, cvs. 'Jinpengchaoguan' and 'Zhongza No. 9', with the former being more tolerant to saline-alkaline stress) seedlings grown hydroponically were subjected to salinity-alkalinity stress condition (NaCl: Na2SO4:NaHCO3:Na2CO3 = 1:9:9:1) without or with foliar application of 0.25 mmol . L-1 spermidine (Spd), and the root morphology and physiological characteristics of mitochondrial membrane were analyzed 8 days after treatment, to explore the protective effects of exogenous Spd on mitochondrial function in tomato roots under salinity-alkalinity stress. The results showed that the salinity-alkalinity stress increased the concentrations of both mitochondrial H2O2 and MDA as well as the mitochondrial membrane permeability in the roots of the two cultivars, while it decreased the mitochondrial membrane fluidity, membrane potential, Cyt c/a and H+-ATPase activity, which impaired the mitochondria and therefore inhibited the root growth; and these effects were more obvious in 'Zhongza No. 9' than in 'Jinpengechaoguan'. Under the salinity-alkalinity stress, foliar application Spd could effectively decrease the concentrations of mitochondrial H2O2 and MDA and mitochondrial membrane permeability, while increased the mitochondrial membrane fluidity, membrane potential, Cyt c/a and H+-ATPase activity. These results suggested that exogenous Spd could effectively mitigate the damage on mitochondria induced by salinity-alkalinity stress, and the alleviation effect was more obvious in 'Zhongza No. 9' than in 'Jinpengchaoguan'. PMID- 27396123 TI - [Effects of Acaulospora spinosa on plant growth and lycopene related genes (psyl and psy2) expression of tomato]. AB - In the present study, an arbuscular mycorrhizal fungus (AMF) strain Acaulospora spinosa XJ27, previously isolated from tomato root rhizosphere in Xinjiang' s suburbs, was used to inoculate root systems of tomato cultivar "Micro-Tom". The biomass, contents of chlorophyll in leaves and lycopene in fruits of plants between the treatments with and without XJ27 were analyzed, and the expression level of lycopene biosynthesis relevant genes (psyl and.psy2) investigated by semi quantitative-PCR and real-time PCR. The results indicated that the application of XJ27 to the rhizosphere of tomato increased the biomass and yield of the treated plants, the expression of psyl and psy2 was improved, and the amount of lycopene accumulation in tomato. It suggested Acaulospora spinosa XJ27 has a great potential in utilization. PMID- 27396124 TI - [Effects of inter-row economic crop planting on soil moisture in a rain-fed jujube orchard in loess hilly region, China]. AB - Soil moisture variation in dryland sloping jujube. orchard was investigated after introducing two economic crops, i.e., feed Brassica napus (JR) and Hemerocallis fulva (JH) planted between jujube rows. Jujube tree without inter-row crop was set as control (CK). The results showed that mean soil moisture for JR and JH in the 0-180 cm soil layer increased by 6.2% and 10.1% compared with CK, respectively. Soil moisture changed mainly in the 0-60 cm soil layer in growth stage of Jujube trees. Soil moisture in JR and JH treatments significantly increased in the 0-60 cm soil layer, which could meet the demand in water resource of jujube plantation. The water consumption of jujube trees also mainly concentrated in the 0-60 cm soil layer. There was a significant decay exponential relationship between the soil moisture in the 0-20 cm layer and the drought duration after rainfall. During the 18-day dry period after rain, the soil moisture contents of JR and JH were apparently higher than that of CK. In conclusion, the jujube-crop intercropping system improved the soil moisture condition. It was an effective measure to overcome the seasonal drought in jujube orchards on the loess hilly region. PMID- 27396125 TI - [Effects of phosphorus fertilization on biomass accumulation and phosphorus use efficiency of trellis-cultivated melon]. AB - A field experiment applying six rates of P fertilizer (P2O5, 0, 150, 225, 300, 375 and 450 kg . hm-2, respectively) was conducted to investigate the effects of P fertilization on dry matter accumulation (DMA), P uptake and accumulation (PUA) and P use efficiency (PUE) of trellis-cultivated melon. Results showed that, P application increased DMA and PUA, for 150 and 225 kg P2O5 . hm-2 treatments, being 19.9% and 26.3%, 23.0% and 26.3% higher than that in no P fertilizer treatment at fruiting stage. With plant growth, DMA and PUA of different organs and the whole plant gradually increased. DMA and PUA were mainly distributed in the leaves during the early stage of the growth and in the fruit during the latter stage. P application decreased the recovery efficiency of applied P (REP), agronomic efficiency of applied P (AEP) and partial factor productivity of applied P (PFP). At 150 kg . hm-2 P application rate, the maximum REP, AEP and PFP were 11.1%, 152.9 kg . kg-1 and 476.3 kg . kg-1, respectively. Compared with no P fertilizer treatment, melon yields of 150 and 225 kg P2O5 . hm2 treatments increased by 47.3% and 39.7%, respectively. In summary, the vining stage and fruit expanding stage were the key periods for P application in trellis cultivated melon system. Based on synthesized economic yield and P fertilizer efficiency, the recommendation of P fertilizer for trellis-cultivated melon is 150-225 kg P2O5 . hm-2 under the climatic condition of the experimental area. PMID- 27396126 TI - [Effects of exogenous melatonin on nitrogen metabolism and osmotic adjustment substances of melon seedlings under sub-low temperature]. AB - The melon cultivar 'Yangjiaosu' was subjected to the treatment of 18 degrees C/12 degrees C (day/night) in an artificial climate chamber for 6 days, and the activities of nitrogen metabolism related enzymes [nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) ] , the contents of total N, NO3(-)-N and NH4+-N as well as the osmotic adjustment substances of melon leaf were then determined. The results showed that, compared with the control, sub-low temperature treatment reduced the contents of total N, NO3(-)-N and the NR activity, but increased the content of NH4(+)-N, thereby leading to the growth inhibition of melon. Exogenous MT treatment significantly improved the activities of nitrogen metabolism related enzymes, especially the activities of GS and GOGAT, effectively reducing the content of NH4+-N. Moreover, MT treatment increased the contents of proline, soluble protein and soluble sugar, and alleviated the damage of sub-low temperature on the cell membrane by reducing the relative electrical conductivity and MDA content of melon leaves. In short, this work suggested that exogenous MT would enhance the sub-low temperature adaptability of melon by decreasing the leaf content of NH4-N, increasing the contents of osmotic adjustment substances and reducing the membrane lipid peroxidation levels. PMID- 27396127 TI - [Hyperspectral parameters and prediction model of soil moisture in coastal saline]. AB - Based on the data of soil moisture content and indoor soil surface spectral reflectance from five sampling sites of coastal saline soil, this paper analyzed the relationship between soil moisture content and soil spectrum in wavelength 350-2500 nm. We determined spectral parameters under ratio spectral index (RSI), normalized difference spectral index (NDSI) and difference spectral index (DI), and established the quantitative model of soil moisture content. The results showed significant negative correlation between spectral reflectance and soil moisture content, and the maximum negative correlation was near 1930 nm (r=0.86). By comparison of the regression equation of RSI, NDSI and DI, it was found that the regression equation of exponential function (y=0.00001e9.7203x) built by soil moisture content based on RSI (R1407, R1459) presented the maximum R2 (0.780) and the minimum SE (0.016). The established model based on RSI (R1407, R1459) could be used to monitor soil moisture content accurately in Jiangsu coastal saline soils. PMID- 27396128 TI - [Distribution of soil organic carbon in surface soil along a precipitation gradient in loess hilly area]. AB - Along the 368-591 mm precipitation gradient, 7 survey sites, i.e. a total 63 investigated plots were selected. At each sites, woodland, grassland, and cropland with similar restoration age were selected to investigate soil organic carbon distribution in surface soil (0-30 cm), and the influence of factors, e.g. climate, soil depth, and land uses, on soil organic carbon distribution were analyzed. The result showed that, along the precipitation gradient, the grassland (8.70 g . kg-1) > woodland (7.88 g . kg-1) > farmland (7.73 g . kg-1) in concentration and the grassland (20.28 kg . m-2) > farmland (19.34 kg . m-2) > woodland (17.14 kg . m-2) in density. The differences of soil organic carbon concentration of three land uses were not significant. Further analysis of pooled data of three land uses showed that the surface soil organic carbon concentration differed significantly at different precipitation levels (P<0.00 1). Significant positive relationship was detected between mean annual precipitation and soil organic carbon concentration (r=0.838, P<0.001) in the of pooled data. From south to north (start from northernmost Ordos), i.e. along the 368-591 mm precipitation gradient, the soil organic carbon increased with annual precipitation 0. 04 g . kg-1 . mm-1, density 0.08 kg . m-2 . mm-1. The soil organic carbon distribution was predicted with mean annual precipitation, soil clay content, plant litter in woodland, and root density in farmland. PMID- 27396129 TI - [Modelling the changes of soil organic carbon under different management practices using Daycent model in North China]. AB - The Daycent model was calibrated and validated using measured crop yield and soil organic carbon (SOC) as double assessment standards based on the experimental data from three long-term experiments (i.e. Zhengzhou site in Henan Province, Yucheng site in Shandong Province and Quzhou site in Hebei Province) in North China. Results showed that the build-up parameters simulated the long-term dynamic changes of crop yields and SOC very well, indicating Daycent model could project the dynamic changes of crop yield and SOC soundly. After calibration and validation, Daycent model was used to simulate the changes of SOC under future climate scenarios (representative concentration pathway 4.5, RCP 4.5) with four different management practices (chemical fertilizer, NPK; chemical fertilizer + organic manure, MNPK; straw incorporation, SNPK; no-tillage +straw incorporation, NT) at the three sites. At Zhengzhou site, the change of SOC was highest for MNPK treatment during the period of 2001-2050 (1.7%) and followed by SNPK (1.3%) and NPK (0.8%) in terms of annual relative increase rate (ARIR), indicating long-term amendment of organic manure could effectively increase SOC for light loam soil with irrigation condition. At Yucheng site, the increase of SOC (ARIR) under MNPK treatment (0.4%) was higher than under NPK treatment (0.3%). In addition, the increase of SOC was very low under all treatments at this site, probably due to light soil salinization. At Quzhou site, the increase of SOC (ARIR) under NT treatment was 1.3%, higher than those under SNPK treatment (0.7%) and NPK treatment (0.4%), indicating NT was more effective for SOC increase in this area. We concluded that no-tillage with straw incorporation is the optimized management practice to increase SOC in North China Plain due to mild climate, sound irrigation and available mechanical equipment for straw processing and no-tillage operation. PMID- 27396130 TI - [Spatial distribution of soil total nitrogen in Liangshui National Nature Reserve based on local model]. AB - Based on LiDAR data of Liangshui National Nature Reserve, digital elevation model (DEM) was constructed and both primary terrain attributes (slope, aspect, profile curvature, etc.) and secondary terrain attributes (wetness index, sediment transport index, relative stream power index, etc.) were extracted. According to the theory of soil formation, geographically weighted regression (GWR) was applied to predict soil total nitrogen (TN) of the area, and the predicted results were compared with those of three traditional interpolation methods including inverse distance weighting (IDW), ordinary Kriging (OK) and universal Kriging (UK). Results showed that the prediction accuracy of GWR (77.4%) was higher than that of other three interpolation methods and the accuracy of IDW (69.4%) was higher than that of OK (63.5%) and UK (60.6%). The average of TN predicted by GWR reached 4.82 g . kg-1 in the study area and TN tended to be higher in the region with higher elevation, bigger wetness index and stronger relative stream power index than in other areas. Further, TN also varied partly with various aspects and slopes. Thus, local model using terrain attributes as independent variables was effective in predicting soil attribute distribution. PMID- 27396131 TI - [Assessment on the yield loss risk of longan caused by cold damage in South China]. AB - Using daily climate variables gathered from 64 meteorological stations in South China from 1961 to 2012, recognized hazard indicators about disaster grades of cold damage for longan, and methods on agricultural meteorological disasters risk and simulation technology, the yield loss risks of longan caused by cold damage in South China during different developmental periods were assessed. The results showed that during the period of physiologic differentiation of flower bud, the disasters of longan affected by mild cold damage in South China were the most common, followed by severe cold damage and moderate cold damage. The hazards caused by cold damage under different grades varied. In particular, under mild cold damage, light disaster of longan was found in Fujian, followed by Guangdong and Hainan, and Guangxi was serious. Under moderate cold damage, light disaster of longan was found in Hainan, followed by Guangdong and Guangxi, and Fujian was serious. Under severe cold damage, light disaster of longan was found in Hainan, followed by Guangdong and Guangxi, Fujian was serious. During the period of morphologic differentiation of flower bud, the disasters of longan affected by mild cold damage in South China were the most common, followed by severe cold damage and moderate cold damage, while the disasters of longan under mild, moderate and severe cold damages within this period were similar. Specifically, light disasters of longan were all found in Hainan, followed by Guangdong, Guangxi and Fujian. During the period of dormancy, the disaster of longan affected by mild cold damage in South China was the most common, followed by severe cold damage and moderate cold damage. Under mild and severe cold damage, light disaster of longan was found in Fujian, followed by Guangdong and Hainan, and Guangxi was serious. However, under moderate cold damage, light disaster of longan was found in Hainan and Guangxi, followed by Guangdong, and Fujian was serious. At the same level of hazard, the largest risk indices of yield loss of longan during different developmental stages significantly differed. Under mild cold damage, serious disasters of longan were found in the period of physiologic differentiation of flower bud, followed by the period of morphologic differentiation of flower bud and the period of dormancy. However, under moderate and severe cold damage, serious disasters of longan were found in the period of physiologic differentiation of flower bud, followed by the period of dormancy and the period of morphologic differentiation of flower bud. PMID- 27396132 TI - [Comprehensive evaluation of improving effects of different organic wastes on a newly reclaimed cultivated land]. AB - There are many problems such as low soil organic matter, available nutrients and microbial activity, compaction, and poor tillage properties for a newly reclaimed cultivated land, and the establishment of a fast, effective measure for improving soil fertility quality is of importance to enhance the quality and production performance of the newly cultivated land. A field experiment was carried out to observe the effect of organic wastes on soil fertility of a newly reclaimed cultivated land, and compared the differences of different types of urban organic wastes. The field experiment included nine treatments, i.e., pig manure, chicken manure, rice straw, vegetable harvest residue, urban sludge, biogas residue, manure+rice straw compost, garbage compost and control without organic fertilizer at annual application rate of 30 t . hm-2, and ran for three consecutive years. The results showed that the application of each type of the eight organic wastes had obvious effects on improving soil fertility. Among them, pig manure, chicken manure, pig manure+rice straw compost, rice straw and biogas residue were the most effective to enhance the carbon pool management index of soil. The addition of pig manure+rice straw compost and biogas residue had the best effect on increasing the soil water stable aggregates and decreasing soil bulk density. Sewage sludge, pig manure+rice straw compost and garbage compost could enhance soil water holding capacity. Pig manure, chicken manure and pig manure+rice straw compost had most obvious effect on increasing soil available nutrients. All kinds of organic wastes increased the number of soil microorganisms and the activity of enzymes. There were some risk of soil heavy metals pollution.for the long-term application of sludge, garbage compost and manure. However, the impact of short term application of the wastes on soil environmental quality was not obvious. Overall, effects of organic wastes on soil fertility decreased in the order of pig manure+rice straw compost>chicken manure>pig manure>biogas residue >garbage compost>rice straw>urban sludge>vegetable harvest residue, and the effects on soil pollution increased in the sequence of rice strawCr>Zn>Ni>As>Pb>Cd. All the maximum ratios of available to total content of elements appeared in surface or -middle to upper layers, except Ni. There was significant positive correlation between available and total contents of target metals. PMID- 27396136 TI - [Meta-analysis of stable carbon and nitrogen isotopic enrichment factors for aquatic animals]. AB - Isotopic enrichment factor (Delta, the difference between the delta value of food and a consumer tissue) is an important parameter in using stable isotope analysis (SIA) to reconstruct diets, characterize trophic relationships, elucidate patterns of resource allocation, and construct food webs. Isotopic enrichment factor has been considered as a constancy value across a broad range of animals. However, recent studies showed that the isotopic enrichment factor differed among various types of animals although the magnitude of variation was not clear. Here, we conducted a meta-analysis to synthesize and compare Delta13C and Delta15N among four types of aquatic animals (teleosts, crustaceans, reptiles and molluscs). We searched for papers published before 2014 on Web of Science and CNKI using the key words "stable isotope or isotopic fractionation or fractionation factor or isotopic enrichment or trophic enrichment". Forty-two publications that contain 140 studies on Delta13C and 159 studies on Delta15N were obtained. We conducted three parallel meta-analyses by using three types of weights (the reciprocal of variance as weights, the sample size as weights, and equal weights). The results showed that no significant difference in Delta13C among different animal types (teleosts 1.0 per thousand, crustaceans 1.3 per thousand, reptiles 0.5 per thousand, and molluscs 1.5 per thousand), while Delta15N values were significantly different (teleosts 2.4 per thousand, crustaceans 3.6 per thousand, reptiles 1.0 per thousand and molluscs 2.5 per thousand). Our results suggested that the overall mean of Delta13C could be used as a general enrichment factor, but Delta15N should be chosen according to the type of aquatic animals in using SIA to analyze trophic relationships, patterns of resource allocation and food webs. PMID- 27396137 TI - [Intestinal bacterial community is indicative for the healthy status of Litopenaeus vannamei]. AB - High density and intensive Litopenaeus vannamei aquaculture has increased the frequency of shrimp disease, however, it remains uncertain whether change in intestinal bacteria could be indicative of shrimp health state (healthy or diseased). Therefore, we collected water and shrimp intestine samples from ponds with or without diseased shrimps. Using bacterial 16S rRNA gene as a biomarker, the bacterial community structure and diversity were evaluated with the Illumina MiSeq sequencing technique. The results showed that the variations of bacterioplankton community were primarily shaped by the levels of NO2(-)-N, chlorophyll a and PO4(3-)-P. Bacterial diversity was signif-7 icantly lower in diseased shrimps than in healthy ones. Using a response ratio analysis, we screened 28 operational taxonomic units (OTUs), and their abundances significantly changed in the intestines between healthy and diseased shrimps. In general, the abundances of OTUs belonged to Actinobacteria, Flavobacteria and Bacilli significantly decreased in diseased shrimps compared with those in healthy shrimps., while the OTUs affiliated to Clostridia showed an opposite pattern. In addition, we obtained 61 indicator species that primarily affiliated to Bacteroidetes, Proteobacteria, Firmicutes, Planctomycetes and Actinobacteria. Notably, the identified indicator taxa exhibited clearly discriminative patterns among habitats (water or intestine) and health status. Collectively, this study provided scientific information for development of new probiotics and disease prevention. PMID- 27396138 TI - [Demographic analysis of the blue shark, Prionace glauca, in the North Atlantic Ocean]. AB - The blue shark, Prionace glauca, is the main by-catch species in tuna longline fishery. As one of top species in the oceanic food webs, the blue shark plays an important role in the marine ecosystem. Traditional stock assessment methods are difficult to accurately evaluate the population dynamic for this shark because of limited data. Based on life-history parameters of the blue shark in the North Atlantic, demographic analysis was employed to estimate the demographic parameters and evaluate the potential exploitation for the blue shark. Moreover, we discussed the relationship between age at first capture and critical value of fishing mortality corresponding to the value of intrinsic rate of natural increase 0. The results showed that the survival rate (S) of blue shark from 0.719 to 0.820, intrinsic rate of natural increase (r0) from 0.250 to 0.381, time of population doubling (tx2) from 1.819 to 2.773 years, reproduction rate per generation (R0) from 6.600 to 22.255, and generation time (G) from 8.498 to 10.162 years. The sensitivity analysis for the life history parameters revealed that the uncertainties of natural mortality existed in the first age class, age at maturity and maximum age had slight influence on the demographic parameters. Fishing mortality (Fc) increased with the age at first capture. When the age at first capture (tc) was more than five, there was no obvious relationship between Fc and tc. PMID- 27396139 TI - [Influence of low temperature and photoperiod on the substances in Locusta migratoria tibetensis]. AB - In order to investigate the adaption of Locusta migratoria tibetensis to the. environment, this paper adopted the experiments with full light exposure (24L/OD), total. darkness (OL/24D), and low temperature (5 degrees C) to study the effects of low temperature and illumination stress on the cold-resistant substances of L. migratoria tibetensis. The results showed that the fat content of L. migratoria tibetensis reached 11.8%, which was the highest under the condition of full light exposure (24L/OD) without low temperature stress. The fat content of body in low temperature and darkness treatment (OL/24D) was 4.7%, which was the lowest. The trehalose, mannitol and sorbitol contents of locust after low temperature stress were significantly higher than that of locust without the same stress. Glycogen content of locust treated by full light exposure without low temperature 'stress was the highest (6.40 mg . g-1). Besides, low temperature and darkness treatment stimulated the accumulation of alanine, glutamic acid, lysine, and phenylalanine, benefiting the accumulation of multi-amino acids, glycerinum, micro-molecule carbohydrate, and the reduction of glycogen and fat content. PMID- 27396140 TI - [Distribution and environmental function of glomalin-related soil protein: A review]. AB - Glomalin-related soil protein (GRSP), a glycoprotein secreted by arbuscular mycorrhizal fungi (AMF), is abundant in soil. GRSP can be fractionated into total glomalin-related soil protein (TG), easily extracted glomalin-related soil protein (EEG), immunoreactive total glomalin (IRTG) and immunoreactive easily extracted glomalin (IREEG). The content of GRSP in soil differed with different soil use type, fertilization condition, AMF and host plant species, and environmental conditions. GRSP significantly positively correlates to the aggregate water stability. GRSP may reduce the release of CO2 in agro-ecosystem, benefit the soil carbon fixation, and reduce the bioavailability and plant toxicity of heavy metals in soil. The extraction and characterization of GRSP are of great importance to understanding the basic behaviors of GRSP in soil environments. Further studies are needed to clarify the molecular biology function of GRSP in agro-ecosystem based on the knowledge of proteins and related genes, and impacts of GRSP on the environmental behavior of organic pollutants in soil. PMID- 27396141 TI - [Eco-physiology and regulation of leaf senescence and maturity performance in cotton: A review]. AB - Senescence is a natural termination process at the plant or organ level of cotton, leading to the inevitable end of the growth and development process. Maturity performance is termed as senescence performance and results of a cotton plant during boll opening, including normal maturity, premature senescence and late-maturity in cotton. Senescence and maturity performance are influenced by genotype and environment interactions. This paper summarized and reviewed the research progress in eco-physiology and molecular biology of cotton leaf senescence. Strategies were proposed to regulate cotton growth and aging through breeding of stably-developed varieties, rational application of plant growth regulators and agronomic cultivation measures, to realize normal maturity and improve yield and quality of cotton. PMID- 27396143 TI - [On evaluating occupational fitness in railway workers with ventricular arrhythmias after coronary arteries stenting]. AB - The authors studied prospects of work capacity preserving after coronary stenting in IHD and cardiac arrhythmias. Examination covered 158 railway workers underwent complete endovascular revascularization of myocardium for coronary stenosis; all of them had ventricular arrhythmias before coronary surgery. Findings are that in long-term period (in 16 months in average) after coronary stenting, grade I and III ventricular extrasystoles disappeared in 77.8 and 54.5% of cases respectively, but only in 11.9% of grade IV ventricular extrasystoles cases. Ventricular extrasystoles remained unchanged in 44.3% of cases. Reliable relationships were seen between unchanged grade IV ventricular extrasystoles and body weight index (OR = 5.49, 95% CI: 0.87-34.67), general cholesterol level (OR = 1.69; 95% CI: 1.06-2.69), low density lipoproteins (OR = 1.66; 95% CI: 1.00 2.76) and left ventricular ejection function lower 45% (OR = 1.61; 95% CI: 1.14 2.27), exertion ventricular extrasystoles before myocardium revascularization (OR = 3.1; 95% CI: 1.78-5.41). That necessitates correction of the mentioned risk factors of cardiac arrhythmias for restored work capacity. PMID- 27396142 TI - [Ecological benefits of the hedgerows: A review]. AB - The hedgerows, also called vegetative barriers, are defined as strips of grass, trees or shrubs or combinations of herbaceous and woody plants established along the contour lines of slopes, the edge of fields, streams, ditches or other water bodies, which can play outstanding roles in soil structure improvement, such as soil texture, porosity, bulk density, and some other physical properties. Its mechanical resistance can delay and intercept runoff effectively, facilitate rainwater infiltration, and reduce the denudation power of runoff on surface land. Moreover, the hedgerows can change sloping topography through constant sediment accumulation at the upper sides of the strips. The international and domestic researches across different ecological zones and geographical regions were summarized and analyzed in this paper. On the basis of such analysis, the hedgerows were confirmed to play a positive role in soil physical and chemical properties, rainfall infiltration, erosion processes, vegetation restoration, biodiversity conservation, landscape optimization and other important ecosystem services. Meanwhile, two problems in the current research of hedgerows were put forward: the planting pattern and structure of hedgerows, species selection, and management practices should be systematized for application, while the mechanisms of hedgerows on vegetation restoration and ecological succession should be further explored in scientific research. PMID- 27396144 TI - [Structure of allostatic load in railway workers]. AB - The authors studied allostatic load in railway workers, as an indicator of stress effect. Analysis covered biomarkers that form allostatic load index, and their ratio for variable allostatic load index levels. Moderate allostatic load appeared to prevail in the examinees group. Findings are that systolic and diastolic blood pressure, general cholesterol and hemoglobin make major contribution into allostatic load index. Comparison covered models of allostatic load index calculation for variable biomarkers sets. PMID- 27396145 TI - [Obstructive sleep apnea features and occupational fitness of railway workers]. AB - The article covers prevalence of obstructive sleep apnea syndrome, its role in health disorders of workers engaged into railway safety. The authors analyzed present standards of occupational fitness in workers performing critically important operating activities and methods of occupational selection with possible obstructive sleep apnea syndrome. I stage recommendations are suggested in diagnosis of obstructive sleep apnea syndrome in workers engaged into railway safety. Obstructive sleep apnea syndrome appeared to threaten operators' activity, to cause accidents, to early disablement due to life-threatening complications, to unsuitability for the occupation due to diseases connected with obstructive sleep apnea syndrome (arterial hypertension, diabetes mellitus, metabolic syndrome, cardiac rhythm and conductivity disorders, obesity). PMID- 27396146 TI - [Possible psychoemotional correction of psychophysical state in railway locomotive crew workers]. AB - The article presents results of study concerning influence of relaxation sessions on emotional and psychophysical state of locomotive crew workers in special cabin for psychoemotional relief "Vivid silence" simulating rest in nature. Relaxation sessions appeared to cause better mood, lower blood pressure, increased reactions speed, reduced number of errors. Purposeful training of the specialists in self regulation is extremely important for preparation to work activity and for prophylactic and social measures aimed to preserve and improve health in locomotive crew workers. PMID- 27396147 TI - [Evaluating influence of Captopril therapy on occupational activity of engine operators with hypertension]. AB - The article covers results of study concerning influence of Captopril (25 mg) therapy on occupational activity of locomotive crew workers in real night travels model on training complex "EP1M locomotive operator cabin". Findings are that single use of Captopril (25 mg) in modelled railway activity enabled to increase reliability of occupational activity, that manifested in lower number of errors in locomotive operators' actions at night, and in psychophysiologic regulation of various psychic acts. PMID- 27396148 TI - [Ethical problems of hygienic tests in occupational medicine]. AB - The authors discuss bioethical problems appearing in usage of genetic tests as a technology of personalized medicine for prevention and early diagnosis of occupational diseases, and connected with question "Who has a right to know results of genetic test?". Analysis covered principles and legal norms, regulating human rights for security of health information, and causes of anxiety about workers' discrimination due to genetic test results. The authors necessitate differentiation between discrimination and reasonable restrictions favorable for workers in cases when work conditions can be a health hazard for person due to genetic predisposition. PMID- 27396149 TI - [Mild cognitive disorders in railway locomotive crew workers (review of literature)]. AB - Functional reliability of engine operator and engine operator's assistant is one of the most important factors in railway safety. Ability to railway locomotive operation is determined via suitability criteria of occupationally important qualities of operator and operator's assistant, and of nervous system functional state. Lower reliability manifested in worse functional state of engine operator or in lost occupationally important qualities can be connected with various diseases of which most prevalent are cardiovascular disorders. Transitory brain circulatory disorders can cause cognitive disturbances varying in severity. When mild cognitive disorders, precise diagnosis leads to effective prevention of the diseases development and preserved occupationally important qualities in engine operators. Neuropsychologic methods for mild cognitive disorders help not only to diagnose presence and intensity of cognitive defect, but to suggest a mechanism of its development, that eventually increases efficiency of correction. PMID- 27396150 TI - [Features of therapy for chronic pancreatitis associated with anxious depressive disorders in railway workers]. AB - The article presents data on peculiarities of chronic pancreatitis course in railway transport workers (engine operators, engine operator assistants, dispatchers) with anxious depressive disorders. Pain and dyspepsia in patients with affective disorders appeared to be constant and more intense than in the patients without concomitant anxious depression. Psychophysiologic tests in 83% of patients with comorbid conditions revealed significant psychomotor dullness manifested in reliable lower speed of visual motor reactions. Pharmacologic correction via anxiolytics (Adaptol, Afobasol) combined with standard therapy for chronic pancreatitis exacerbation enabled to improve clinical symptoms, but Adaptol appeared to slow simple visual motor reactions, therefore has to be ruled out in engine operators. Pharmacotherapy of chronic pancreatitis, that included Afobasol in addition to standard treatment, promoted reliable improvement of occupationally important psychophysiologic functions. This study received a patent. PMID- 27396151 TI - [Complex use of naphthalane and nonselective chromotherapy in gonarthrosis treatment in rolling stock workers]. AB - Complex treatment using naphthalane applications with nonselective chromotherapy covered 64 engine operators of locomotive crews, aged 40-69 years, having 1-3 stage knee osteoarthrosis. Findings are that optimized treatment schedules effectively reduce intensity of pain, improve functional state of the joints involved, increase life quality of the patients, have no side effects. Comparative analysis of the treatment results showed that efficiency of combined naphthalane and nonselective chromotherapy exceeds isolated naphthalane effects. PMID- 27396152 TI - [Structure and dynamics of occupational morbidity in Bashkortostan Republic]. AB - The authors represent data on analysis of dinamics and structure of occupational incidence in Bashkortostan Republic, according to archive documents of Ufa Research Institute of Occupational Health and Human Ecology, on occupational morbidity dynamics over 2008-2014, on its regional peculiarities. PMID- 27396153 TI - [Formation and implementation of youth science policy in occupational medicine in Russia]. AB - The authors present manterials on youth movement in medical science, on this trend development priorities in governmental policy, on main historical moments of its formation, on events for young scientists and specialists, their role in advances and implementation of research work. These topics are exemplified on youth participation in medical science, hygiene and science on workers' health preservation--occupational medicine. PMID- 27396154 TI - [Genomic Characterization of an Unusual Human G3P[3] Rotavirus with Multiple Cross-species Reassortment]. AB - One unusual human G3P[3] group A rotavirus (RVA) strain M2-102 was identified in stool sample collected from a child with diarrhea in Guangxi Province, China in 2014. It is well known that G3P[3] is a genotype commonly identified in feline and canine RVAs. However, the preliminary phylogenetic analyses of the VP7 and VP4 genes of strain M2-102 indicated that these two genes were closely related to bat RVA strain MYAS33 and simian strain RRV, respectively, whereas both clustered distantly to feline/canine-like RVA strains. In this study, full genome sequencing and molecular analyses were conducted to obtain the true origin of strain M2-102. It was revealed that strain RVA/Human-wt/CHN/M2-102/2014/G3P[3] exhibited a G3-P[3]-I3-R3-C3-M3-A9-N3-T3-E3-H6 genotype constellation for VP7-VP4 VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes. Phylogenetic analyses revealed that 5 genes (VP7, VP1, VP2, NSP2 and NSP3) from strain M2-102 were closely related to those of bat strain MYAS33 from Yunnan Province which was thought a true bat RVA strain rather than a virus transmitted between species, while another 5 genes (VP4, VP3, NSP1, NSP4 and NSP5) clustered closely with those of simian strain RRV, yet the VP6 gene was closely related to that of human G3P[9] strain AU-1 and AU-1-like RVAs. The epidemiological data indicated that the child infected with M2-102 came from a countryside village, located in Dong Autonomous County of Sanjiang (subtropical hilly wooded area), Liuzhou city in Guangxi Province which might provide natural environment for reassortment events occurring among animal and human RVAs. Therefore, the data suggest that human strain M2-102 might originate from multiple reassortment events among bat, simian and human AU-1-like RVAs, yet it is not clear whether the genomic backbone based on bat MYAS33 (5 genes) and simian RRV (5 genes) like rotaviruses had been obtained through reassortment before being transmitted to the human. This is the first report on whole genome analysis of human G3P[3] RVA from China. PMID- 27396155 TI - [Preparation and Identification of High Immunogenic A/PR/8/34 Maternal Strain HA Protein for Influenza Virus Classical Reassortment]. AB - Preparation of maternal strain A/PR/8/34 HA antiserum for influenza virus classical reassortment. A/PR/8/34 virus was digested by bromelain after inactivation and purification. 5%-20% sucrose continuous density gradient centrifugation method was used to purify HA protein. SIRD method was used to select the target protein. SDS-PAGE method was used to identified HA protein. High Immunogenic A/PR/8/34 HA protein was successfully prepared and HI titer reached 10240. High purity HA antiserum was identified by SIRD method. The key reagent in the classical reassortment of influenza virus was prepared, and the complete set of technical methods were explored, which laid the foundation for the independent research and development of seasonal influenza vaccine strains of China. PMID- 27396156 TI - [Genetic Characteristics of Coxsackievirus Group A Type 4 Isolated from Patients with Acute Flaccid Paralysis in Shaanxi, China]. AB - We analyzed the genetic characteristics of coxsackievirus A4 (CV-A4) based on the entire VP1 coding region. Samples were isolated from patients with acute flaccid paralysis (AFP) in Shaanxi, China from 2006 to 2010. We wished to ascertain the predominant genotype and the relationship between CV-A4 infection and AFP. Sixty eight non-polio enteroviruses were inoculated onto RD cells (to increase the virus titer) and molecular typing was undertaken. The entire VP1 coding region was amplified. Percentage of CV-A4 was 10.3% (7/68). Analyses of genetic identify and creation of phylogenetic trees revealed that CV-A4 could be classified into A, B and C genotypes. Seven CV-A4 strains from Shaanxi and other CV-A4 strains from China formed an independent evolution lineage located in group 4 and belonged to the C2 sub-genotype. These data suggested that CV-A4 strains of sub genotype C2 were the predominant genotypes in China. These strains co-evolved and co-circulated with those from other provinces in China, so continued monitoring of CV-A4 (by clinical and genetic surveillance) should be enhanced. PMID- 27396157 TI - [Generation of Japanese Encephalitis Virus-like Particle Vaccine and Preliminary Evaluation of Its Protective Efficiency]. AB - The cDNA fragment of JEV prME gene was cloned into the baculovirus shuttle vector (bacmid) to construct a recombinant baculovirus vector, defined as AcBac-prME. Then the recombinant baculovirus Ac-prME was obtained by transfecting Sf9 cells with AcBac-prME. Western blot analysis and immunofluorescence results indicated that both prM and E proteins were efficiently expressed in Sf9 cells. Electron microscopy suggested that prME was assembled into JEV-VLPs. To further evaluate the potential of JEV-VLPs as vaccine, the mice were immunized with JEV-VLPs and then challenged with lethal JEV. The results of mice survival and pathological changes demonstrated that the JEV-VLPs performed complete protection against JEV P3 strain and relieved pathological changes in the mice brain significant. This study suggest that JEV-VLPs would be a potential vaccine for Japanese encephalitis virus. PMID- 27396158 TI - [Whole-sequence Analyses for 12 HBV C/D Recombinants from a Population in Tibet (China)]. AB - We wished to undertake molecular genetic typing and evaluate recombinants of the hepatitis-B virus (HBV) in Tibet (China). Multistage random sampling was used to collect HBsAg-positive samples. Nested polymerase chain reactions were used to amplify the whole sequence of the HBV. DNAstar, MEGA6 and SimPlot were used to assemble sequences, create phylogenetic trees, and undertake recombination analyses. Twelve whole sequences of the HBV of a Tibetan population were collected using these methods. Results showed that all 12 strains were C/D recombinants. Nine of the recombinations were at nt750, and the other three at nt1526. Therefore, the 12 strains could be divided into two types of recombinants: C/Da and C/Db. Analyses of the sequence of the whole genome revealed that the 12 strains belonged to genotype C, and that the nucleotide distance was > 4% between the 12 strains and sub-genotypes C1 to C15 in Genbank. The most likely sub-genotype was C1. Individuals with C/Da were from central and northern Tibet (e.g., Lasa, Linzhi, Ali) and those with C/Db recombinants were from Shannan in southern Tibet. These data suggest that the two types of recombinants had a good distribution in Tibet. Also, they can provide important information for studies on HBV recombination, gene features, virus evolution, as well as the control and prevention of HBV infection in Tibet. PMID- 27396159 TI - [Characterization and Analyses of the Full-length Genome of a Strain of the Akabane Virus Isolated from Mosquitoes in Yunnan Province, China]. AB - We wished to sequence the full-length genomes of the DHL10M110 strain of the Akabane virus (AKV) isolated from mosquitoes in Yunnan Province, China, in 2010. We also wished to analyze the characteristics of these complete nucleotide sequences. The complete genomic sequence of the DHL10M110 strain from Yunnan Province was obtained by reverse transcription-polymerase chain reaction and direct sequencing. We found that the length of the L, M and S gene nucleotide sequences of the DHL10M110 strain were 6 869-bp, 4 309-bp and 856-bp, respectively, including the open reading frame (ORF) nucleotide sequences of 6 756-bp (L), 4 206-bp (M) and 702-bp (S), encoding 2252, 1402 and 234 amino-acid polyproteins, respectively. Phylogenetic analyses based on L-fragment ORF showed that the DHL10M110 strain had a close relationship with the OBE-1 strain of the AKV from Japan and AKVS-7/SKR/2010 strain of the AKV from South Korea. Phylogenetic analyses based on M- and S-fragment ORF showed that the DHL10M110 strain had a close relationship with the epidemic strains of the AKV from Japan, South Korea and Taiwan, but that the DHL10M110 strain had a lone evolutionary branch. In terms of nucleotide (amino acid) homology, the similarity of L-, M- and S-fragment ORFs of the DHL10M110 strain to the OBE-1 strain from Japan was 92.6% (98%), 88.5% (94%) and 96.4% (99.1%), respectively. When comparing the DHL10M110 strain with the OBE-1 strain, we noted 45, 84, and 2 different sites in the amino acids of L, M and S fragments, respectively. Homology and phylogenetic analyses also suggested that the DHL10M110 strain had a distant relationship with the epidemic strains of the AKV from Kenya and Australia. Also, we confirmed by complete genomic sequence analyses that the DHL10M110 strain was clade-Asia of the AKV. However, differences between the DHL10M110 strain compared with strains from Japan and South Korea were also noted. These results suggest that the DHL10M110 strain harbored relatively stable genetic characteristics and distinct regional features. This is the first time that full-length genomic sequences of the DHL10M110 strain of the AKV in mainland China have been obtained. PMID- 27396160 TI - [Study on Cellular Immune Responses of DNA Vaccine, rAd5 and rMVA Expressing SIV Gag/Env Gene Combined Immunization in Mice]. AB - Therapeutic HIV vaccine was considered as a hopeful curative method for AIDS patients. However, there is still no suitable HIV animal model for vaccine study since the difference in the immune system between human and animals. To evaluate the therapeutic effect of combined immunization strategy with multiple vector vaccines in macaque models. Plasmid DNA, recombinant Ad5 and MVA vaccines which expressing SIV gag and env genes were constructed. Sequential and repeated immune strategy were applied to immunize mice with these three vaccines. Cellular immune responses in mice immunized with these three vaccines were measured by ELISPOT test in vitro and CTL assay in vivo. The results were analyzed and compared with different antigen combination, order of vaccines and intervals to choose a suitable immunization strategy for macaque immunization in future. It indicated that strong SIV-Gag/Env-specific cellular immune responses were induced by these three vector vaccines. It laid a foundation for evaluating the therapeutic effect of combined immunization strategy with multiple vector vaccines in SIV infected macaque models. PMID- 27396161 TI - [SH and HN Protein Genetic Characterization Analysis of Mumps Virus Isolated in Liaoning Province from 2008 to 2014]. AB - To analyze the genetic characterization of epidemic mumps virus strains in Liaoning Province and provide the basis for mumps control. A total of 32 mumps viruses strains were isolated during 2008-2104. The fragment of SH genes and HN genes were amplified by RT-PCR, the PCR products were sequenced and analyzed. Basing on the 316 nucleotides of SH gene, The phylogenetic analyses were processed with the data of WHO mumps reference strains downloaded from GenBank and 32 mumps viruses strains. It showed that the 31 mumps virus strains belong to F genotype except MuVi/Liaoning. CHN/16.11 which was G genotype . Comparing to the A reference strains (Jeryl-Lynn and S-79), F genotype MuV were mutated on 12 amino acids sites and 27 amino acids siteson on HN gene. F genotype MuV added one N-glycosylation site in 464th-466th amino acids. The antigenic sites on HN were mutated on 121th, 123th, 279th, 287th, 336th, 356th and 442th. Maybe, it will influence the MuV antigenic. PMID- 27396162 TI - [Detection of Yersinia Enterocolitica Bacteriophage PhiYe-F10 Lysis Spectrum and Analysis of the Relationship between Lysis Ability and Virulence Gene of Yersinia Enterocolitica]. AB - To determine the lysis spectrum of Yersinia enterocolitica bacteriophage phiYe F10 and to analyze the relationship between the lysis ability of phiYe-F10 and the virulence gene of Yersinia enterocolitica. To observe the lysis ability of the phage phiYe-F10 to the different Yersinia strains with the double-layer technique. The strains used in this study including 213 of Yersinia enterocolitica and 36 of Yersinia pseudotuberculosis and 1 of Yersinia pestis. The virulence genes of these Yersinia enterocolitica (attachment invasion locus (ail) and enterotoxin (ystA, ystB) and yersinia adhesin A (yadA), virulence factor (virF), specific gene for lipopolysaccharide O-side chain of serotype O : 3 (rfbc) were all detected. Among the 213 Yersinia enterocolitica, 84 strains were O : 3 serotype (78 strains with rfbc gene), 10 were serotype O : 5, 13 were serotype O : 8, 34 were serotype O : 9 and 72 were other serotypes. Of these, 77 were typical pathogenic Yersinia enterocolitica harboring with virulence plasmid (ail+, ystA+, ystB-, yadA+, virF+), and 15 were pathogenic bacterial strains deficiency virulence plasmid (ail+, ystA+, ystB-, yadA-, virF-) and the rest 121 were non pathogenic genotype strains. PhiYe-F10 lysed the 71 serotype O : 3 Yersinia enterocolitica strains which were all carried with rfbc+, including 52 pathogenic Yersinia enterocolitica, 19 nonpathogenic Y. enterocolitica. The phiYe F10 can not lysed serotype O : 5, O : 9 and other serotype Y. enterocolitica, the lysis rate of serotype O : 3 was as high as 84.5%. The phiYe-F10 can not lysed Yersinia pseudotuberculosis and Yersinia pestis. Yersinia phage phiYe-F10 is highly specific for serotype O : 3 Yersinia enterocolitic at 25 degrees C, which showed a typical narrow lysis spectrum. Phage phiYe-F10 can lysed much more pathogenic Y. enterocolitica than nonpathogenic Y. enterocolitica. PMID- 27396163 TI - [Effect of Low Dose of Chicken Infectious Anemia Virus in Attenuated Vaccine on SPF Chicken Body Weight and Vaccine Immune Antibody]. AB - In order to observe the effect of the immune and weight of chickens after use the attenuated vaccine with low dose of chicken infectious anemia virus (CIAV). In this study, the effects of low dose of CIAV on the weight of SPF chickens and NDV antibody production were observed by simulated experiments. The results showed that 10 EID50 and 5 EID50 CIAV per plume attenuated NDV vaccines were used to cause the weight loss of SPF chickens. Compared with the use of the non contaminated vaccine group, it has significant difference. And NDV antibody levels compared with the use of the non contaminated groups also decreased after use the vaccine with two doses of CIAV contaminated. It has significant difference. A certain proportion of CIAV antibody positive was detected at the beginning of the second week after use the NDV vaccine with two doses of CIAV contaminated. The detection of a high proportion of CIAV nucleic acid was detected in the first week after the use of a contaminated vaccine. The results of the study demonstrate the effects of CIAV pollution on the production and immune function of SPF chickens, and it is suggested that increasing the detection of viral nucleic acid can help save time and improve the detection rate in the detection of exogenous virus contamination by SPF chicken test method. PMID- 27396165 TI - [The Isolation and Identification of Infectious Bronchitis Virus PTFY Strain in Muscovy Ducks]. AB - In July 2009, some farms of breeding Muscovy ducks on the peak of egg laying suffered the decrease of hatching rate and the quality of the eggs showing low mortality and no evident respiratory symptoms. The swelling and congestive ovary was visible after autopsy. This study was brought out for the diagnosis of these cases. The virus was isolated and identified by the methods of virus culture in chicken embryo, physical and chemical properties test, hemagglutinin test, NDV (Newcastle diseases Virus) interference test, electron microscope observation, pathogenicity test and the gene sequence analysis. The results indicated the virus showed the characters of inducing dwarf embryo after inocubation, the sensibility to lipid solvent and the hemagglutination capacity after pancreatic enzyme treatment, the typical morphology of coronavirus, the interference to NDV replication and the homology among 84.7% - 99% of the particial N gene sequences to the reference IBV (Avian infectious bronchitis virus) strains. The strain was identified as IBV isolate and this study confirmed the pathogenicity of IBV to Muscovy ducks. PMID- 27396164 TI - [Immune Response of Recombinant Pseudorabies Virus rPRV-VP2 Expressing VP2 Gene of Porcine Parvovirus in Mice]. AB - In order to develop a combined live vaccine that will be used to prevent against porcine parvovirus (PPV) and Pseudorabies virus (PRV) infection, the VP2 gene of PPV was inserted into the transfer vector plasmid pG to produce the recombinant plasmid pGVP2. The plasmid pGVP2 and the genome of PRV HB98 attenuated vaccine were transfected by using lipofectamine into swine testis cells for the homologous recombination. The recombinant virus rPRV-VP2 was purified by selection of green fluorescence plaques for five cycles. 6-week-old female Kunming mice were immunized intramuscularly with attenuated PRV parent HB98 strain, commercial inactivated vaccine against PPV, recombinant virus, DMEM culture solution. The injections were repeated with an equivalent dose after 2 weeks in all of the groups, and then challenged with the virulent PRV NY strain at 7 weeks after the first immunization. The recombinant virus rPRV-VP2 was successfully generated, and the recombinant virus could effectively elicite anti PPV and PRV antibody and significant cellular immune response as indicated by anti-PPV ELISA and HI, PRV-neutralizing assay and flow cytometry. The challenge assay indicated that recombinant virus could protect the mice against the virulent PRV challenge. These results demonstrated that the recombinant virus can be a candidate recombinant vaccine strain for the prevention of PRV and PPV. PMID- 27396167 TI - [Inhibition of HBV Release by BST-2]. AB - Bone marrow stromal antigen 2 (BST-2) is a kind of host restriction factor. Since it was discovered to be responsible for the defect in virion release of HIV-1 mutants lacking the accessory gene vpu in 2008, it was thought to mainly restrict the viruses by directly tethering viral particles at the plasma membrane. Recent reports suggest that BST-2 also can inhibit the the release of HBV particles, which are budding in the intracellular vesicles, expanding the antiviral spectrum of BST-2. Futhermore, the machanism that BST-2 used to restrict HBV release in multivesicular bodies (MVBs) is similar to that used to restrict HIV at the plasma membrane. However, HBV have evolved strategies to antagonize the antiviral action of BST-2. There are two different opinions about the antagonist. One is HBV inactivated BST-2 by HBx requiring a hepatocyte-specific environment. Another thought envelope protein HBs counteract the antiviral action of BST-2. In this review, we focus on the current advances in the anti-HBV activity of BST-2. PMID- 27396166 TI - [Establishment of Quality Control System of Nucleic Acid Detection for Ebola Virus in Sierra Leone-China Friendship Biological Safety Laboratory]. AB - The quality control process throughout the Ebola virus nucleic acid detection in Sierra Leone-China Friendship Biological Safety Laboratory (SLE-CHN Biosafety Lab) was described in detail, in order to comprehensively display the scientific, rigorous, accurate and efficient practice in detection of Ebola virus of first batch detection team in SLE-CHN Biosafety Lab. Firstly, the key points of laboratory quality control system was described, including the managements and organizing, quality control documents and information management, instrument, reagents and supplies, assessment, facilities design and space allocation, laboratory maintenance and biosecurity. Secondly, the application of quality control methods in the whole process of the Ebola virus detection, including before the test, during the test and after the test, was analyzed. The excellent and professional laboratory staffs, the implementation of humanized management are the cornerstone of the success; High-level biological safety protection is the premise for effective quality control and completion of Ebola virus detection tasks. And professional logistics is prerequisite for launching the laboratory diagnosis of Ebola virus. The establishment and running of SLE-CHN Biosafety Lab has landmark significance for the friendship between Sierra Leone and China, and the lab becomes the most important base for Ebola virus laboratory testing in Sierra Leone. PMID- 27396168 TI - [Research Progress on Antiviral Activity of Interferon-induced Transmembrane Proteins]. AB - Interferon-induced Transmembrane Proteins (IFITMs) were identified through small interference RNA (siRNA) screening method in 1980s. The antiviral properties of the IFITMs were firstly discovered in 1996. Recently, its antiviral effect and mechanism have become a research hotspot. Many studies have shown that IFITM can inhibit the replication of multiple pathogenic viruses, including influenza A virus (IAV), Human Immunodeficiency Virus (HIV-1), hepatitis C virus (HCV), Ebola virus (EBOV), West Nile virus and so on. IFITMs inhibit the replication of virus in the early stage of the viral life cycle, which occurred before the release of viral genomes into the cytosol. Recent studies indicate that IFITM proteins could block viral replication by mediate viral membrane fusion. However, the mechanism is still under investigation. Here we review the discovery and characterization of the IFITM proteins, elucidate their antiviral activities and the potential mechanisms. PMID- 27396169 TI - [Research Advances in Target Genes of Epstein-Barr Virus-encoded MicroRNAs]. AB - The Epstein-Barr virus (EBV) is a gamma herpes virus associated with several types of malignancies. The EBV encodes viral microRNAs (miRNAs) that can target genes within cells. The EBV participates in signal transduction as well as the proliferation and differentiation of cells. How the target genes and functions of EBV-encoded miRNAs contribute to the pathogenesis of EBV is an important research topic. Some target genes have been validated since EBV-encoded miRNAs were discovered and, in this article, we summarize them and their functions. PMID- 27396170 TI - [HTLV-1 bZIP Factor (HBZ): Roles in HTLV-1 Oncogenesis]. AB - Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV 1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action. PMID- 27396171 TI - [Research Advances in the Porcine Deltacoronavirus]. AB - The deltacoronavirus is a new member of the subfamily Coronaviridae of the family Coronaviridae. Deltacoronaviruses can infect birds and mammals. Deltacoronaviruses were detected in early 2007 in Asian leopard cats and Chinese ferret badgers. In 2014, porcine deltacoronavirus (PDCoV) infection spread rapidly in the USA. Moreover, cell culture-adapted PDCoV has been obtained from infected piglets. Animal experiments have confirmed that the isolated PDCoV is highly pathogenic and causes severe diarrhea in piglets. Thus, the PDCoV can be considered to be a good model to study the deltacoronavirus. In this review, we discuss the etiology, epidemiology, pathogenicity, culture, and diagnostic methods of the PDCoV. PMID- 27396172 TI - [Sympatric Speciation of the Plague Microbe Yersinia pestis: Monohostal Specialization in the Host-Parasite Marmot-Flea (Marmota sibirica-Oropsylla silantiewi) System]. AB - An ecological scenario of the origin of the plague microbe that is interpreted in the light of modern Darwinism (synthetic theory of evolution) is presented. It is shown that the plague microbe emerged from a clone of the psychrophilic saprozoonotic pseudotuberculosis microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan time, 22000-15000 years ago, in the monohostal Mongolian marmot (Marmota sibirica)-flea (Oropsylla silantiewi) host-parasite system. It was noted that the evolutionary process described corresponds to the sympatric form of speciation by transition ofthe clone of migrant founders to a new, already-existing ecological niche. It was established that monohostal specialization of the plague microbe was made possible due to heterothermia (5-37 degrees C) of marmots in the hibernation period. The factors of the speciation process--isolation, the struggle for existence, and natural selection--were analyzed. PMID- 27396173 TI - [Neurons with Different Neurotransmitters in Embryonic Neocortical Allografts in the Rat Sciatic Nerve]. AB - Different subsets of interneurons in the Wistar rat neocortex and in neocortical transplants developing in a damaged nerve were identified by the following immunohistochemical markers: glutamate decarboxylase (GAD 67) for GABAergic nerve cells, NO-synthase (NOS) for NO-ergic neurons, choline acetyltransferase (ChAT) for cholinergic cells, and tyrosine hydroxylase for catecholaminergic structures. Twenty-eight days after surgery, individual GAD 67-ir, NO-ir, ChAT-ir, and very rarely TH-ir cells were detected in the graft. It was shown that the number of GAD 67-ir neurons per unit area in the grafts was less than in the rat neocortex P20. PMID- 27396174 TI - [The Role of Ombrophilic Dissipotrophic Bacteria in Wood Decomposition]. AB - The summarized experimental data on ombrophilic bacteria isolated from dystrophic waters formed by a mycobacterial community during the process of spruce wood decomposition are presented. It was demonstrated that the ombrophilic microbial community was characterized by wide phylogenetic diversity at the initial stage of spruce wood decomposition by xylotrophic fungi under low mineralization conditions. It was noted that bacteria were able to grow under acidic and ultrafresh conditions and most of them were referred to oligotrophs. It was determined that all isolated ombrophilic bacteria divided into three groups depending on the substrate specifity: saccharolytic, acidotrophic bacteria, and bacteria, which used C1-compounds as the substrate. The position of the ombrophilic bacteria in the trophic chain was determined. PMID- 27396175 TI - [Impact of Radioactive Elements on Microbial Complexes in Cryogenic Soils of Yakutia]. AB - It has been found that microorganisms in cryogenic soils of Yakutia are resistant to the long-term impact of cesium and thorium. The number of microorganisms in the studied ecological-trophic groups does not depend on the concentrations of radioactive elements. Differences in the number of microorganisms are determined by the physicochemical conditions that are created in different horizons of the soils studied. The long-term impact of radiation (for 36 and 66 years) on microorganisms inhabiting the permafrost soils of Yakutia has developed their adaptive capacity to high concentrations of these radioactive elements. PMID- 27396176 TI - [A Complex Morpho-Histological Approach to the In Vitro Study of Morphogenic Structures in a Wheat Anther Culture]. AB - The external morphological and internal histological features of morphogenic structures (embryoids, calli with embryoids, and calli with buds and roots) have been studied in vitro in a wheat anther culture by light microscopy. The results of this study have been compared with data obtained earlier by scanning electron microscopy. PMID- 27396177 TI - [The Microsculpture of Glochidia of Some Anodontine Bivalves (Unionidae)]. AB - Glochidia of three freshwater anodontine bivalves: Kunashiria Starobogatov in Zatrawkin, 1983, Sinanodonta Modell, 1944, from the Far East, and Anodonta Lamarck, 1799, were investigated by scanning electron microscopy. Data on the microsculpture of the outer surface of glochidial valves are given. Among the three genera discussed, the glochidia of Anodonta are the largest, with a loose looped outer microsculpture and numerous granules. The glochidia of Kunashiria and Sinanodonta differ by the valve height--length proportions and some details of the outer microsculpture: glochidia of Kunashiria have a tight-looped outer sculpture while the glochidia of Sinanodonta have a loose-net outer sculpture. PMID- 27396178 TI - [Revision of the Taxonomic Position of the Olkhon Mountain Vole (Rodentia, Cricetidae)]. AB - An analysis of the phylogenetic position of the Olkhon mountain vole (Alticolaolchonensis Litvinov 1960) using the sequences of four nuclear (BRCA, GHR, LCAT, and IRBP) and one mitochondrial (cyt. b) genes was undertaken. It was noted that, until recently, multiple studies of the systematic position of this vole had been based exclusively on morphological data, while the major taxonomic traits contained contradictory information regarding both the subgeneric status of this species and its genus. It was established that the molecular data and morphology data allow us to attribute the Lake Baikal vole unambiguously to the nominative subgenus Alticola instead of Aschizomys. PMID- 27396179 TI - [Characteristics of the Effect of Cestodes Parasitizing the Fish Intestine on the Activity of the Host Proteinases]. AB - The activity and spectrum of proteinases in the intestines of host fishes change upon infestation with cestodes. Serine proteinases are found to make a greater contribution to the total proteolytic activity. The reduction of proteolytic activity is associated with adsorption of the enzymes of the host on the surface of cestodes, and the increase in the activity is caused by the injury of the intestinal mucosa by the attachment apparatuses of cestodes. The inhibition of proteainase activity indicates the possible participation of microbiota enzymes in protein hydrolyses. PMID- 27396180 TI - [Extreme Climatic Events in the Altai Republic According to Dendrochronological Data]. AB - The results of dating of extreme climatic events by damage to the anatomical structure and missing tree rings of the Siberian larch in the upper forest boundary of the Altai Republic are given. An analysis of the spatial distribution of the revealed dates over seven plots (Kokcy, Chind, Ak-ha, Jelo, Tute, Tara, and Sukor) allowed us to distinguish the extreme events on interregional (1700, 1783, 1788, 1812, 1814, 1884), regional (1724, 1775, 1784, 1835, 1840, 1847, 1850, 1852, 1854, 1869, 1871, 1910, 1917, 1927, 1938, 1958, 1961), and local (1702, 1736, 1751, 1785, 1842, 1843,1874, 1885, 1886, 1919, 2007, and 2009) scales. It was shown that the events of an interregional scale correspond with the dates of major volcanic eruptions (Grimsvotn, Lakagigar, Etna, Awu, Tambora, Soufriere St. Vinsent, Mayon, and Krakatau volcanos) and extreme climatic events, crop failures, lean years, etc., registered in historical sources. PMID- 27396181 TI - [The Spatial Variability of Methane Emission from Grass-Moss Fens of the Subtaiga and Forest-Steppe of Western Siberia]. AB - Emission of methane from the grass-moss fens of the Western Siberia subtaiga was studied using a static chamber method. It was established that a median half of the interquartile range of the specific flow of CH4 in the studied wetland ecosystems constituted 4.9 +/- 2.9 mg of CH4/(m2 x h). It was shown that such a high spatial variability of emission is caused mainly by the difference in the level of fen waters. It was found that, in these observations, a higher level of the water stand correlates with lower emission values. The causes of this phenomenon are discussed, and recommendations for conducting field studies for estimating the regional flow are given. PMID- 27396182 TI - [Flora Differentiation among Local Ecotopes in the Transzonal Study of Forest Steppe and Steppe Mounds]. AB - Flora similarity was assessed using complete floristic lists of five ecotopes in each of four mounds along the transect from meadow steppes to desert steppes. It was found that the circumapical similitude of floras is more significant than the expositional similitude. Soil analysis in separate ecotopes showed that regular changes in the biogeochemical features are manifested along the topographic gradient and under the effect of the insolation exposure of slopes in local (mound) ecosystems. It was noted that the slopes are characterized by the most abundant steppe vegetation classes in the phytosociological spectrum of mound ecotopes. PMID- 27396183 TI - [Carbon Isotope Composition in Landscape Components and Its Changes under Different Ecological Conditions]. AB - The composition of stable carbon isotopes in plants, plant litter, leaf litter, and soil organic matter was studied experimentally in the western part of the northern foothills of the Caucasus and mountainsides. It was found that the changes in carbon isotope composition depending on the vertical zonation do not exceed 8 per thousand and depend on the type of C3 plant communities, its presence in biogeocenosis components (living matter, plant litter, soil organic matter), and the degree of moistening of the plot studied. PMID- 27396184 TI - The Terpenoid Biosynthesis Toolkit of Trichoderma. AB - The widely used biotechnologically important fungi belonging to the genus Trichoderma are rich sources of secondary metabolites. Even though the genomes of several Trichoderma spp. have been published, and data are available on the genes involved in biosynthesis of non-ribosomal peptide synthetases and polyketide synthases, no genome-wide data are available for the terpenoid biosynthesis machinery in these organisms. In the present study, we have identified the genes involved in terpene biosynthesis in the genomes of three Trichoderma spp., viz., T. virens, T. atroviride and T. reesei. While the genes involved in the condensation steps are highly conserved across the three species, these fungi differed in the number and organization of terpene cyclases. T. virens genome harbours eleven terpene cyclases, while T. atroviride harbours seven, and T. reeseisix in their genomes; seven, three and two being part of putative secondary metabolism related gene clusters. PMID- 27396185 TI - Anti-angiogenic Activity and Mechanism of Sesquiterpene Lactones from Centipeda minima. AB - Centipeda minima is a Chinese herbal medicine used in the treatment of various diseases including cancer. An ethanol extract of the herb, its four fractions with different polarities, and two volatile oils prepared by steam distillation (SD) and supercritical fluid extraction (SFE) were investigated for their anti angiogenic activity in a wild-type zebrafish model using a quantitative endogenous alkaline phosphatase (EAP) assay. The SFE oil displayed potent anti angiogenic activity. Fifteen sesquiterpene lactones (SLs; compounds 1-15) isolated from the SFE oil were evaluated for their anti-angiogenic effect. Results revealed that pseudoguaianolide type SLs (1-8) inhibited vessel formation in the zebrafish embryos while guaianolide type SLs (9-15) showed little effect. Among the active ones, 6-O-angeloylenolin (1), a major component of SFE oil, possessed the strongest effect by reducing vessel formation in zebrafish embryos to 40% of the control value at 29.7 uM. Further study using the Tg (fli1a:EGFP) y1-type zebrafish model revealed that it blocked both intersegmental blood vessels (ISVs) and subintestinal vessels plexus (SIVs) formation in zebrafish embryos. Real-time polymerase chain reaction assay on the wild-type zebrafish embryos suggested that 6-O-angeloylenolin affected multiple molecular targets related to angiogenesis including VEGF receptor, angiopoietin, and its receptors. Taken together, our findings demonstrate that C. minima possesses anti-angiogenic activity, and 6-O-angeloylenolin is a promising candidate for the development of an anti-angiogenic agent. PMID- 27396186 TI - Bis-sesquiterpene from the Marine Sponge Dysidea fragilis. AB - Two new sesquiterpenes and one new bis-sesquiterpene, named dysinidins C-E (1-3) along with three known sterols, dysideasterol F, 9alpha,l lalpha-epoxycholest-7 en-3beta,5alpha,6alpha-triol, and 9alpha,11alpha-epoxycholest-7-en 3beta,5alpha,6alpha,19-tetrol 6-acetate (4-6) were isolated from the Vietnamese marine sponge Dysidea fragilis (Montagu, 1814). Their structures were determined by 1D- and 2D-NMR spectroscopies and HR-ESI-MS, as well as by comparison with reported literature data. Compounds 4-6 were found to inhibit eight human cancer cell lines (KB, LU-1, HL-60, LNCaP, SK-Mel-2, HepG-2, MCF-7, and PC-3), with IC50 values ranging from 7.3 to 31.5 uM. PMID- 27396187 TI - Two New Compounds from the Leaves of Glochidion obliquum. AB - Using combined chromatographic methods, two new compounds, 6beta,9beta:9,13 diepoxymegastig-4-en-3beta-ol (1), 5a,6a-epoxy D:C-friedoolean-8-en-3beta-ol (2) were isolated from the methanol extract of the leaves of Glochidion obliquum Decne. Their structures were elucidated by 1D- and 2D-NMR spectra and in comparison with those reported in the literature. PMID- 27396188 TI - A Norsesterterpene Peroxide from a Marine Sponge Hippospongia sp. AB - One new norsesterterpene peroxide, rhopaloic acid H (1), along with two known related metabolites 2 and 3, were isolated from a marine sponge Hippospongia sp. The structures of compounds were elucidated by means of IR, MS, and NMR techniques and comparison of the NMR data with those of known analogues. Evaluation of the cytotoxicities revealed that compound 2 exhibited significant cytotoxicity against DLD-1, Molt 4, T47D and K-562 cell lines, with IC50 values of 3.18, 0.69, 2.22 and 1.06 ug/mL, respectively. Moreover, compound 3 also showed significant K562 inhibitory activity, with IC50 value of 3.65 ug/mL. PMID- 27396189 TI - A Novel Tirucallane-type Triterpene and Sesquiterpene from Trichilia maynasiana. AB - One new tirucallane-type triterpene {3beta, 24-dihydroxytirucallan-7,25-diene, 24 sulfate (1)}, one new sesquiterpene {7-epi-10-hydroxychabrol-1(2)-en-4,5-dione A (2)}, together with three known tirucallanes, and four aromadendranes were isolated from the leaves of Trichilia maynasiana C. DC.. Their structures were determined by means of NMR spectroscopy, mass spectrometric analysis, and chemical methods. PMID- 27396190 TI - Stereospecific Oxidation of Diacetoxyheterobetulin with Ozone and Dimethyldioxirane. AB - Stereospecific oxidation of diacetoxyheterobetulin with ozone and dimethyldioxirane led to 3beta,28-diacetoxy-18alpha,19betaH-urs-20alpha,21alpha epoxide with yields of 79% and 87%, respectively. Oxidation with ozone was not selective and gave two minor products containing 2lalpha-hydroxy-20(30)-ene and 21a-hydroxy-20beta,28-epoxy-fragments in ring E. The structures of 3beta,28 diacetoxy-18alpha,19betaH-urs-20alpha,21alpha-epoxide and 3beta-diacetoxy-21alpha hydroxy-20beta,28-epoxy-18alpha,19betaH-ursane were confirmed by X-ray analysis for the first time. PMID- 27396191 TI - Effectiveness of 5-Pyrrolidone-2-carboxylic Acid and Copper Sulfate Pentahydrate Association against Drug Resistant Staphylococcus Strains. AB - Bacterial resistance is an ongoing challenge for pharmacotherapy and pharmaceutical chemistry. Staphylococcus aureus is the bacterial species which makes it most difficult to treat skin and soft tissue infections and it is seen in thousands of hospitalization cases each year. Severe but often underrated infectious diseases, such as complicated nasal infections, are primarily caused by MRSA and S. epidermidis too. With the aim of studying new drugs with antimicrobial activity and effectiveness on drug resistant Staphylococcus strains, our attention in this study was drawn on the activity of a new association between two natural products: 5-pyrrolidone-2-carboxylic acid (PCA), naturally produced by certain Lactobacillus species, and copper sulfate pentahydrate (CS). The antimicrobial susceptibility test was conducted taking into account 12 different Staphylococcus strains, comprising 6 clinical isolates and 6 resistant strains. PCA 4%, w/w, and CS 0.002%, w/w, association in distilled water solution was found to have bactericidal activity against all tested strains. Antimicrobial kinetics highlighted that PCA 4%, w/w, and CS 0.002% association could reduce by 5 log10 viable bacterial counts of MRSA and oxacillin resistant S. epidennidis in less than 5 and 3 minutes respectively. Microscopic investigations suggest a cell wall targeting mechanism of action. Being very safe and highly tolerated, the natural product PCA and CS association proved to be a promising antimicrobial agent to treat Staphylococcus related infections. PMID- 27396192 TI - Effect of Selected Pyrazine Derivatives on the Production of Phenolics and Rutin in Urtica dioica and Fagopyrum esculentum. AB - The effect of four pyrazine derivatives on the content of phenolic compounds in Urtica dioica L. and rutin in Fagopyrum esculentum Moench was studied. Pyrazine derivatives H1 and H2 were used on U. dioica, and derivatives S1 and S2 on F. esculentum, both separately and in combination with urea. The content of phenolic compounds in the stems of U. dioica after treatment with H2 at a concentration of 10(-3) M significantly increased compared with the control and to a lower concentration of the same pyrazine derivative. In the case of S1 and S2 for F. esculentum, rutin content also increased in stems, mainly after treatment together with urea. By contrast, rutin and phenolics contents in the leaves did not change in comparison with controls after application of H1, H2, S I and S2. Treatment with H1 and H2 in two chosen concentrations resulted in a significant increase in the net photosynthetic rate, transpiration rate and stomatal conductance. A slight increase in the rate of photosynthesis was observed also after application of variants of S1 and S1 with urea. Pyrazine derivatives did not show any effect on either the relative content of chlorophyll or chlorophyll fluorescence. A slight weight reduction of above ground biomass was shown only after application of Si and S2. Dark necrosis on the edges and center of the leaves was observed in all treated plants after pyrazine application. The results suggest that all the pyrazine derivatives possess herbicidal effects. PMID- 27396193 TI - A New Diketopiperazine, Cyclo(D-trans-Hyp-L-Leu) from a Kenyan Bacterium Bacillus licheniformis LB 8CT. AB - Bacterially-produced small molecules demonstrate a wide range of structural and functional diversity. A new diketopiperazine, cyclo(D-trans-Hyp-L-Leu) (1), and five other known diketopiperazines (2-6), were isolated and purified from the fermented broth of a Kenyan bacterium Bacillus licheniformis LB 8CT. The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including 2D NMR and HR-MS, and the absolute configuration was determined by a combination of NOESY analysis and Marfey's method. The known compounds were identified as cyclo(D-cis-Hyp-L-Leu) (2), cyclo(D-cis-Hyp-L-Phe) (3), cyclo(D-Pro-L-Tyr) (4), cyclo-(D-Trp-L-Leu) (5), and cyclo(L-Tyr-Gly) (6) by comparison of their spectroscopic and physical data with reported values. Compounds 1-6 were tested for antifungal and antimicrobial properties. PMID- 27396194 TI - Aerobic Decomposition of Trialkylquercetins: Structure Characterization and Antiproliferative Effect. AB - The aerobic decomposition of 3,4',7-O-trialkylquercetins was first reported in this paper. The structures of four new decomposed products were characterized by analyzing the 1D and 2D NMR data, as well as their high resolution mass spectroscopic data. Their antiproliferative activity toward human prostate cancer cells has been assessed through WST-l cell proliferation assay. The decomposition mechanism was also proposed. PMID- 27396195 TI - Evaluation of Radical Scavenging Activity of Sempervivum tectorum and Corylus avellana Extracts with Different Phenolic Composition. AB - Semnpervivum tectorum L. and Corylus avellana L. are traditional herbal remedies exhibiting antioxidant activity and representing diverse phenolic composition. The aim of this study was to reveal the contribution of certain compounds to total radical scavenging activity by studying S. tectorum and C. avellana extracts prepared with solvents of different selectivity for diverse classes of phenolics. Antioxidant activity of S. tectorum and C. avellana samples was determined in the ABTS and DPPH radical scavenging assays, and phenolic composition was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Correlations between antioxidant activity and phenolic content of houseleek extracts have been revealed. Significant differences regarding antioxidant activity have been shown between S. tectorum 80% (v/v) methanol extract and its fractions. Additionally, synergism among the constituents present together in the whole extract was assumed. Significantly higher radical scavenging activity of hazel extracts has been attributed to the differences in phenolic composition compared with houseleek extracts. PMID- 27396196 TI - Chemical Constituents from the Roots, Stems and Leaves of Diplomorpha sikokiana. AB - Four diarylpentanoids (1-4), two phenylpropanoids (5-6), three biflavonoids (7 9), two lignans (10-11) and a coumarin (12) were isolated from the roots of Diploniorpha sikokiana (Franchet & Savatier) Honda (Family: Thymelaeaceae). Similarly, two phenylpropanoids (5-6), five biflavonoids (7-9, 13, 14), three lignans (11, 15, 16), a flavonoid (17) and two coumarins (12, 18) were isolated from the stems, and five flavonoids (17, 19-22) from the leaves. Among them, 1,5 diphenyl-l-pentanone (1), 1,5-diphenyl-2-penten-l-one (2), 3(S)-hydroxy-1,5 diphenylpentane (3), stelleranol (8), (-)-syringaresinol (10), (-)-pinoresinol 4,4'-di-O-beta-D-glucopyranoside (11), apiosylskimmin (12), syringaresinol 4-O beta-D-glucopyranoside (16), quercetin 3-O-alpha-L-rhamnopyranoside (19), kaempferol 3-0-alpha-L-rhamnopyranoside (20) and tiliroside (21) were isolated for the first time from D. sikokiana. PMID- 27396197 TI - Two New Phenanthrene Glucosides from Cremastra appendiculata and their Cytotoxic Activities. AB - Two new phenanthrene glucosides, named 2'-hydroxy-4,4',7'-trimethoxy-1, l' biphenanthrene-2,7-di-O-beta-D-glucoside (1) and 1-(4-hydroxybenzyl)-4-methoxy 2,7-dihydroxy-phenanthrene-8-O-beta-D-glucoside (2), together with three known compounds were isolated from the tubers of Cremastra appendiculata (D.Don) Makino. Their structures were elucidated on the basis of spectral data. Compounds 1-4 showed moderate cytotoxic activity and compound 5 showed weak cytotoxic activity against the two cell lines tested. This is the first reported occurrence of an unusual biphenanthrene glucoside in this plant. PMID- 27396198 TI - Two New Anthraquinones from the Roots of Prismatomeris connata. AB - Two new anthraquinones, 4-hydroxy-1,2,3-trimethoxy-7-hydroxymethylanthracene-9,10 dione (1) and 1,2,3-trimethoxy-7-hydroxymethylanthracene-9,10- dione (2), were isolated from the roots of Prismatomeris connata, a Chinese medicinal herb. Their structures were elucidated by spectroscopic analysis. Compound 1 exhibited cytotoxicity against a panel of H1229, HTB 179, A549 and H520 lung tumor cell lines with IC50 values ranging from 12.3 to 20 uM. PMID- 27396200 TI - Two New Compounds from Artemisia sacrorum. AB - Two new compounds, named as sacric acid A (1) and sacric acid B (2), were isolated from the EtOAc extract of Artemisia sacrorum Ledeb. This is the first report on the structure elucidation of these compounds based on UV, IR, and extensive ID and 2D NMR spectroscopic, and ESI-MS techniques. PMID- 27396199 TI - HPLC-Guided Isolation, Purification and Characterization of Phenylpropanoid and Phenolic Constituents of Nutmeg Kernel (Myristica fragrans). AB - Many studies on the biological activities of nutmeg continue to appear in the literature. The most common targets include GIT, CNS, oxidative stress and inflammation. However, results obtained from most studies are often inconsistent due to the variability of utilized samples, lack of standardized nutmeg products or insufficient amounts of pure compounds for comprehensive follow-up investigation. To address the consistency and supply issue we utilized available technology to develop a reproducible procedure for preparation of specific extracts and isolation of the major phenolic constituents present in nutmeg kemel. A well-defined and reproducible sequence of extraction, fractionation and chromatographic purification was adopted and was guided by HPLC fingerprinting. Spectroscopic methods, mainly NMR, and mass spectrometry were utilized to identify each compound. Thirteen compounds were isolated in a pure form and identified as: elemicin (1), isoelemicin (2), myristicin (4), surinamensin (5), malabaricone C (6), 2-(3'-allyl-2',6'-dimethoxy-phenyloxy)-l- acetoxy-(3,4 dimethoxyphenyl)-propyl ester (7), methoxylicarin A (8), licarin A (9), malabaricone B (10), licarin C (11), 5'-methoxylicarin B (12), licarin B (13), and 2-(3'-allyl-2',6'-dimethoxy-phenyloxy)-l-methyl-5-methoxy-1,2 dihydrobenzofuran (3, a new compound). With repeated isolation runs, these pure compounds can be prepared in quantities sufficient for biological evaluation as needed. The availability of purified compounds will also allow the development of specific, accurate, and sensitive analytical procedures for pharmacokinetic studies and for quality control of nutmeg products. Both aspects are essential for nutmeg-focused drug discovery. The same approach can also be adapted to other medicinal plants of potential interest. PMID- 27396201 TI - Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells. AB - In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4-475.0 uM for MG63 cells and from 798.7-359.9 uM for Saos2 cells). PMID- 27396202 TI - Activity of the Lichen Usnea steineri and its Major Metabolites against Gram positive, Multidrug-resistant Bacteria. AB - The antimicrobial activity and possible synergistic effects of extracts and compounds isolated from Usnea steineri were evaluated against four resistant bacterial species. A phytochemical study of the acetone extract of U. steineri resulted in the isolation and characterization of difractaic acid and (+)-usnic acid as the main compounds. The acetone extract showed strong activity (less than 10 ug/mL) against resistant strains of Staphylococcus epidermidis and Enterococcus faecalis, and (+)-usnic acid exhibited strong activity against S. epidermidis (MIC 3.12 ug/mL), S. aureus and S. haemnolyticus (MIC 12.5 ug/mL). Combinations of penicillin and tetracycline with (+)-usnic acid did not show any synergistic antimicrobial effects. Difractaic acid was inactive. Our results showed that the acetone extract of U. steineri possesses significant in vitro antimicrobial activity, which is likely related to the presence of (+)-usnic acid. PMID- 27396203 TI - A New Succinate Derivative from Ajuga decumbens. AB - A new succinate derivative, ethyl (5-formylfuran-2-yl)methyl succinate (1), along with three known compounds (2-4) have been isolated from the whole plants of Ajuga decumbens Thunb. Their structures were elucidated by extensive spectroscopic (1D and 2D NMR) and HR-ESI-MS data analysis, and literature values. Compound 1 was isolated as a new succinate derivative, and compounds 2 and 3 were for the first time separated from A. decumbens. PMID- 27396204 TI - Chlorogenic Acid Interaction with Cisplatin and Oxaliplatin: Studies in Cervical Carcinoma Cells. AB - The antiproliferative effect of the naturally occurring polyphenol chlorogenic acid (CGA) was evaluated in combination with either cisplatin or oxaliplatin in human cervical carcinoma cell lines that were either sensitive (A431) or resistant to cisplatin (A431Pt), in order to provide evidence to overcome drug resistance. Cytotoxicity of platinating drugs (IC50 - 10(-6) - 10(-5) M) was enhanced by 1-2 orders of magnitude by increasing incubation times (1, 4, and 24 hours) in the two cell lines. CGA treatment presented low cytotoxicity per se (IC50 ~ 10(-4) M at 24 h) if compared with platinum drugs and its activity was similar in A431Pt cells and in their sensitive A431 counterpart. The combination of the platinating drugs with CGA (10(-6) - 10(-4) M) indicated variable effects on cytotoxicity, ranging from potentiation to various degrees of antagonism (in A431 cells) and no effect (in A431Pt cells). In order to explain the different cytotoxic activity elicited by oxaliplatin and cisplatin in association with CGA, the possible presence of chemical interactions was investigated by HPLC analysis. The drug association with CGA caused evident changes in their chromatographic profile, suggesting occurrence of in vitro chemical interactions. PMID- 27396205 TI - In Vitro and In Vivo Antiangiogenic Activity of Crowberry (Empetrum nigrum var. japonicum). AB - Crowberry, Empetrum nigrum var. japonicum, is widely used in folk medicine and grows naturally in Korea. Although some constituents and biological activity of Korean crowberry have been examined, there is little detailed information available. In this study, we investigated the effects of ethanol extracts of crowberry (EECB) on the inhibition of angiogenesis, both in vitro and in vivo. The effects of EECB were tested on in vitro models of angiogenesis, that is, tube formation and proliferation of human umbilical vein endothelial cells (HUVECs). EECB exhibited significant inhibitory effects on tube formation of HUVECs in a concentration-dependent manner. In addition, crowberry significantly suppressed the proliferation of HUVECs in a concentration-dependent manner. Furthermore, strong antiangiogenic activity of EECB samples was observed in the in vivo assay using chick embryo chorioallantoic membrane (CAM). These results indicate that crowberry may have potential applications in the prevention and treatment of angiogenesis-dependent human diseases. PMID- 27396206 TI - Search for beta-Secretase Inhibitors from Natural Spices. AB - The growing number of Alzheimer's disease (AD) patients prompted us to seek effective natural resources for the prevention of AD. We focused on the inhibition of beta-secretase, which is known to catalyze the production of senile plaque. Sixteen spices used in Asian countries were selected for the screening. Among the extracts tested, hexane extracts obtained from turmeric, cardamom, long pepper, cinnamon, Sichuan pepper, betel, white turmeric and aromatic ginger showed potent inhibitory activities. Their active principles were identified as sesquiterpenoids, monoterpenoids, fatty acid derivatives and phenylpropanoids using GC-MS analyses. The chemical structures and IC50 values of the compounds are disclosed. The results suggest that long-term consumption'of aromatic compounds from spices could be effective in the prevention of AD. PMID- 27396207 TI - The Effect of Camellia Seed Oil Intake on Lipid Metabolism in Mice. AB - Camellia seed oil has mainly been applied to the production of cosmetics, and research into its dietary effects is required. Alterations in lipid metabolism by the intake of camellia seed oil were investigated. Health parameters such as diet intake, weight gain, fat mass, and plasma cholesterol and triglyceride levels were measured in mice fed a high fat diet containing camellia seed oil; comparisons were made to a normal diet and a high fat diet containing either soybean oil or olive oil as controls. No significant differences in weight gain and diet intake were observed between the groups. However, the camellia seed oil diet suppressed epididymal fat weight similarly to the olive oil diet. In total cholesterol and HDL (high density lipoprotein) cholesterol levels, the soybean oil, olive oil and camellia seed oil diet groups showed significant increases compared with the normal diet. However, increases in LDL (low density lipoprotein) cholesterol levels were inhibited by the camellia seed oil diet similarly to the olive oil diet. As the high oleic acid content of camellia seed oil is similar to that of olive oil, it is proposed that its presence mitigated fat accumulation and plasma cholesterol levels. PMID- 27396208 TI - Essential Oil Compositions and Antimicrobial Activities of Various Parts of Litsea cubeba from Taiwan. AB - The essential oils of leaves, fruits, flowers, stems and twigs of Litsea cubeba were extracted by hydrodistillation. A total of 53, 50, 76, 94 and 90 compounds were identified from the leaf, fruit, flower, stem and twig oils, respectively, and their yields were 13.9 +/- 0.09, 4.0 +/- 0.03, 10.4 +/- 0.05, 0.09 +/- 0.01 and 0.4 +/- 0.02 mL/100 g of the oven-dried (o.d.) materials, respectively. The main component in the leaf, flower and twig oils was 1,8-cineole, whereas in the fruit oil it was citral, and in the stem oil limonene, citronellal, and citronellol. When tested for their antibacterial activities using the paper disc diffusion method, oils from all parts showed excellent activities, particularly the fruit oil. When the oils were infused onto filter paper and tested for their antimicrobial paper capability according to the JIS L 1902 method, the fruit oil exhibited excellent antimicrobial activities. Citral was deemed the main cause of the antimicrobial activity. With the multiplicity of contagious diseases and their prevalence in hospitals, these essential oils present a potentially good choice as antibacterial agents. We think that the essential oils of this species are capable of multipurpose applications. PMID- 27396209 TI - Antimicrobial Activity and Chemical Analysis of the Essential Oil of Algerian Juniperus phoenicea. AB - The essential oils of Juniperus phoenicea L. from Algeria were obtained by hydrodistillation and analyzed by GC-FID and GC-MS. Concerning their chemical composition, 74, 61 and 72 volatile compounds were identified from fresh leaves, dried leaves and berries, representing 88.8%, 91.3% and 94.7% of the total composition, respectively. The main monoterpene in the oils of fresh leaves, dried leaves and berries was a-pinene (29.6% / 55.9% / 56.6%), accompanied by lesser amounts of the sesquiterpenes beta-caryophyllene (2.6% / 1.6% /1.2%) and germacrene D (2.01% / 1.7% / 1.5%), respectively. Antibacterial activity of J. phoenicea essential oils was tested against one Gram-negative and four Gram positive bacterial strains and the yeast Candida albicans, responsible for nosocomial infections. As references, 14 antibiotics and 5 antifungal agents were evaluated. The berry essential oil was ineffective against all but two of the strains tested, whereas the essential oil of dried leaves significantly inhibited all strains but Pseudomonas aeruginosa, which turned out to be the most resistant strain overall. However, Escherichia coli was the most susceptible to the essential oils tested. The essential oil of dry leaves was highly active against Candida albicans, outclassing even the standard antifungal substances. These promising results could substantiate the use of essential oils in the treatment of hospital-acquired infections. PMID- 27396210 TI - Antifungal Screening of Lavender Essential oils and Essential Oil Constituents on three Post-harvest Fungal Pathogens. AB - A growing body of literature indicates that many synthetic pesticides have adverse effects on human, animal, and environmental health. As a result, plant derived natural products are quickly gaining momentum as safer and less ecologically damaging alternatives due to their low toxicity, high biodegradability, and good specificity. Essential oils of Lavandula angustifolia, Lavandula x intermedia cv Grosso, and Lavandida x intermedia cv Provence as well as various mono- and sesquiterpene essential oil constituents were tested in order to assess their antifungal potential on three important agricultural pathogens: Botrytis cinerea, Mucor piriformis, and Penicillium expansum. Fungal susceptibility testing was performed using disk diffusion assays. The majority of essential oil constituents tested did not have a significant effect; however, 3 carene, carvacrol, geraniol, nerol and perillyl alcohol demonstrated significant inhibition at concentrations as low as 1 u/mL. In vivo testing using strawberry fruit as a model system supported in vitro results and revealed that perillyl alcohol, carvacrol and 3-carene were effective in limiting infection by postharvest pathogens. PMID- 27396211 TI - Chemical Composition and Bioactivity of the Essential Oils of Heracleum pyrenaicum subsp. pollinianum and Heracleum orphanidis. AB - The objective of this research was to analyze the chemical composition, antimicrobial and cytotoxic activity of Heracleun pyrenaicum subsp. pollinianum (Bertol.) F. Pedrotti & Pignatti (HPP) and H. orphanidis Boiss. (HO) essential oils. The composition of the oils was analyzed by GC and GC-MS. beta-Pinene (35.1%) was the most abundant compound in HPP root oil, while (Z)-falcarinol (80.0%) dominated in HO root oil. (E)-Nerolidol (28.5%) was the main constituent in HPP leaf oil. HPP fruit oil, as well as HO leaf and fruit oils mainly contained aliphatic esters, mostly octyl acetate (50.5-84.5%). Antimicrobial screening was performed by microdilution method against eight bacterial and eight fungal strains. The strongest antibacterial activity was shown by both root oils (MICs 0.02-0.60 mg/mL and MBCs 0.04-2.50 mg/mL for HPP, and MICs 0.02-1.25 mg/mL and MBCs 0.04-2.50 mg/mL for HO), while the best antifungal potential was exhibited by HPP fruit oil (MICs 0.30-0.60 mg/mL and MFCs 0.60-1.25 mg/mL) and HO leaf oil (MICs 0.15-0.63 mg/mL and MFCs 0.30-1.25 mg/mL). The tested root and fruit oils exhibited strong cytotoxic effect, which was determined by MTT test against HeLa (IC50 7.53-21.07 ug/mL) and LS174 (IC50 24.16-58.86 ug/mL) cell lines. PMID- 27396212 TI - Composition and Biological Activity of Volatile Oil from Salviajudaica and S. multicaulis from Jordan. AB - The aim of this work was to determine the composition of the hydro-distilled essential oil of Salvia judaica Boiss. and S. multicaulis Vahl. (Lamiaceae) from Jordan by GC and GC-MS and to report the actual composition of their fresh leaves and flowers using SPME (Solid Phase Micro-Extraction).Their dual alpha amylase/alpha glucosidase and pancreatic lipase inhibitory activities as well as their anti-proliferative potential were screened. The aroma profile of the leaves, flowers, and flowers at pre-flowering stages of S. judaica, obtained through SPME was composed of sesquiterpene hydrocarbons (87.7 %, 71.8 %, and 86.2 %, respectively) while the hydro-distilled oil of the dry leaves was rich in oxygenated sesquiterpenes (50.8%). Fresh leaves of S. multicaulis were rich in oxygenated monoterpenes (58.1%), while monoterpene hydrocarbons dominated the blooming flowers (57.2%) and the flowers at the pre-flowering stage (64.7%). The hydro-distilled oil of the dry leaves was rich in oxygenated monoterpenes (77.6%). With doxorubicin as a positive control, no anti-proliferative activity was observed against colorectal cancer cell lines HT29, HCT116, and SW620 using SRB assay for either Salvia spp. In vitro enzymatic starch digestion was evaluated with Acarbose (IC50: 0.2 +/- 0.0 ug /mL) as the reference drug. The respective IC50 (mg/mL) values of S. judaica and S. multicaulis aqueous extracts were 4.9 +/- 0.4 and 10.3 +/- 0.9. Modulation of pancreatic lipase activity (PL) was determined by colorimetry and compared with Orlistat (IC50 : 0.11 +/- 0.0 ug/mL). PL-IC50 values (ug/mL) obtained for S. judaica and S. multicaulis were 108.5+/-6.4 and 31.8 +/- 0.8, respectively. PMID- 27396213 TI - Anti-adipocyte Differentiation Activity and Chemical Composition of Essential Oil from Artemisia annua. AB - Arteinisia annua L. essential oil (AAEO) has diverse properties including antibacterial, antioxidant, antinociceptive, and antimicrobial activities. However, the effect of AAEO on obesity remains to be investigated. In this study, we analyzed the compounds of AAEO and explored the effect of AAEO on the differentiation of preadipocyte into adipocyte using preadipocyte cell line 3T3 L1. Total yield of AAEO from 20 kg A. annua leaf and flower was 0.5%, v/w. Gas chromatography-mass spectrometry analysis showed that AAEO contained 34 compounds. 3T3-LI cells incubated in 3-isobutyl-l-methylxanthine / dexamethasone / insulin (MDI)-containing medium showed increased accumulation of lipid droplets. This increased response was suppressed by treatment with AAEO. Expressions of obesity-related proteins (PPARgamma, C/EBPalpha, SREBP-1c, FAS, and ACC) were increased in 3T3-LI cells cultured in MDI medium and these responses were decreased by treatment with AAEO. These findings demonstrate that AAEO may suppress 3T3-LI cell differentiation by inhibiting adipogenesis and activation of lipid metabolism-related proteins. PMID- 27396214 TI - Essential Oil Chemical Composition and Headspace Volatiles Profile of Achillea coarctata from Serbia. AB - This study reports the essential oil composition and headspace volatiles profile of Achillea coarctata Poir. from Serbia. The inflorescences, stems and leaves, and the aerial parts of A. coarctata were analyzed separately. Germacrene D, alpha-terpineol and 1,8-cineole were the main constituents of the aerial parts essential oil; 1,8-cineole, cis-cadin-4-en-7-ol and alpha-terpineol were the most dominant compounds in the inflorescence essential oil, while the most abundant components in the stem and leaf oil were germacrene D, cis-cadin-4-en-7-ol and ledol. The percentages of monoterpenoids and sesquiterpenoids in the aerial parts were the same, while there were differences in distribution of these compound classes in inflorescence and stem and leaf essential oils. The major components of the headspace volatiles were the same for aerial parts, inflorescence and stem and leaves: 1,8-cineole, beta-pinene and alpha-pinene. PMID- 27396215 TI - Preisocalamendiol, Shyobunol and Related Oxygenated Sesquiterpenes from Bolivian Schinus molle Essential Oil. AB - Five batches of Bolivian Schinus molle essential oils were obtained from pilot and industrial-scale hydrodiffusions. They were analyzed by gas chromatography to find 80 known compounds and two unknown molecules. In particular, preisocalamendiol (5.6-11.0 %) was found to be an important constituent of these oils, along with shyobunol (0.6-3.2 %) and several other related oxygenated sesquiterpenes. These compounds, usually found in Acorus calamus, had not been reported altogether in S. molle essential oils previously. These findings, in light of the GABAA positive modulating effect of shyobunone and preisocalamendiol, along with some traditional uses of S. molle, suggest that further investigation of the tranquilizing properties of these Bolivian oils would be of interest. PMID- 27396216 TI - Comparative Chemical Analysis of Mentha piperita and M. spicata and a Fast Assessment of Commercial Peppermint Teas. AB - The hydrodistilled essential oils and volatile compounds (by static headspaces technique) of Mentha piperita L. and M spicata L. were characterized by GC-MS. Headspace analysis of Mentha piperita revealed the existence of menthone (25.4%), 1,8-cineole (17.7%) and menthol (12.1%) as the main components, while the essential oil contained high amounts of menthol (46.8%) and menthone (25.6%). By contrast, headspace analysis of M. spicata showed a high content of limonene (37.0%) together with carvone (13.0%), beta-pinene (10.4%) and alpha-pinene (9.8%), while the essential oil was reach in carvone (51.7%), dihydrocarveol (11.5%) and cis-dihydrocarvone (9.1%). Eleven samples of peppermint tea available on the Romanian market were analysed by headspace GC-MS. The volatile profile of the tea samples was compared with that of Mentha piperita L. and certain differences were emphasized and discussed. PMID- 27396217 TI - Antiherpetic Plants: A Review of Active Extracts, Isolated Compounds, and Bioassays. AB - Herpes simplex is a disease that is widely distributed throughout the world. It is caused by herpes simplex virus type 1 (HSV-1) and simplex virus type 2 (HSV 2). The drugs of choice for treatment are acyclovir (ACV), Penciclovir (PCV) and other guanine analogues, which have the same mechanism of action. However, due to the constant increase of ACV-resistant strains in immunocompromised patients, it is necessary to find new treatment alternatives. It has been shown that natural products are a good alternative for the treatment of these diseases as well as being an excellent source of compounds with anti-herpetic activity, which may be useful for the development of new drugs and act through a mechanism of action different from ACV and PCV. This paper compiles reports on extracts and compounds isolated from plants that have anti-herpetic activity. We present an analysis of the solvents most widely used for extraction from plants as well as cells and commonly used methods for evaluating cytotoxic and anti-herpetic activity. Families that have a higher number of plants with anti-herpetic activity are evaluated, and we also highlight the importance of studies of mechanisms of action of extracts and compounds with anti-herpetic activity. PMID- 27396218 TI - The Obstetrics and Neonatal Outcomes of Teenage Pregnancy in Naresuan University Hospital. AB - OBJECTIVE: It is evident that the incidence of teenage pregnancy has been increasing in the past decades and consequently poses significant problems on maternal and child health. The present study was aimed to compare obstetric and neonatal outcomes between teenage and non-teenage pregnancy. MATERIAL AND METHOD: A retrospective cohort study was conducted to investigate 957 singleton pregnant women attending labor rooms in Naresuan University Hospital between October 2006 and September 2013 by comparing the pregnancy outcomes of 268 teenage pregnancy (woman age less than 20 years at the first time of antenatal care visit) with 689 non-teenage pregnancy (woman age 20 to 34 years). The obstetrics and neonatal complication was the main outcome of interest. RESULTS: The incidence of teenage pregnancy was 15.24% during seven years of study. As opposed to non-teenage mothers, complete attending antenatal care visit was less likely to be found among teenage mothers, 66.5% vs. 90.5% respectively (p < 0.001). Higher proportion of normal vaginal delivery was found in teenage mothers (59.7% vs. 36.4%). The occurrence of cephalo-pelvic disproportion (CPD) seemed to be lower in teenage group as compared to non-teenage group, 14.5% vs. 26.4% (p < 0.001). In addition, postpartum hemorrhage was unlikely to occur in teenage group, 3.8% vs. 8.4% (p = 0.016). The proportion of preterm birth was found to be higher in teenage pregnancy compared to non-teenage pregnancy (16.2% vs. 5.5%, p < 0.001). At birth, the higher proportion of infants who had low Apgar scores (< 7) at 1 minute was found in teenage pregnancy, 7.1% vs. 3.1% (p = 0.01). CONCLUSION: Even though obstetric complications were less likely to occur among teenage pregnancies, most of the neonatal untoward consequences were observed in mothers with younger ages. The finding suggests the need of appropriate health care services for teenage mothers as to monitor harmful complications to both mother and her child. PMID- 27396219 TI - Accuracy of ICD-10 Coding System for Identifying Comorbidities and Infectious Conditions Using Data from a Thai University Hospital Administrative Database. AB - OBJECTIVE: To determine the accuracy of International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system in identifying comorbidities and infectious conditions using data from a Thai university hospital administrative database. MATERIAL AND METHOD: A retrospective cross-sectional study was conducted among patients hospitalized in six general medicine wards at Siriraj Hospital. ICD-10 code data was identified and retrieved directly from the hospital administrative database. Patient comorbidities were captured using the ICD-10 coding algorithm for the Charlson comorbidity index. Infectious conditions were captured using the groups of ICD-10 diagnostic codes that were carefully prepared by two independent infectious disease specialists. Accuracy of ICD-10 codes combined with microbiological dataf or diagnosis of urinary tract infection (UTI) and bloodstream infection (BSI) was evaluated. Clinical data gathered from chart review was considered the gold standard in this study. RESULTS: Between February 1 and May 31, 2013, a chart review of 546 hospitalization records was conducted. The mean age of hospitalized patients was 62.8 +/- 17.8 years and 65.9% of patients were female. Median length of stay [range] was 10.0 [1.0-353.0] days and hospital mortality was 21.8%. Conditions with ICD-10 codes that had good sensitivity (90% or higher) were diabetes mellitus and HIV infection. Conditions with ICD-10 codes that had good specificity (90% or higher) were cerebrovascular disease, chronic lung disease, diabetes mellitus, cancer HIV infection, and all infectious conditions. By combining ICD-10 codes with microbiological results, sensitivity increased from 49.5 to 66%for UTI and from 78.3 to 92.8%for BS. CONCLUSION: The ICD-10 coding algorithm is reliable only in some selected conditions, including underlying diabetes mellitus and HIV infection. Combining microbiological results with ICD 10 codes increased sensitivity of ICD-10 codes for identifying BSI. Future research is needed to improve the accuracy of hospital administrative coding system in Thailand. PMID- 27396220 TI - Incidence and Predictors of Long-Term Adverse Outcomes in Patients with Rheumatic Mitral Stenosis in Sinus Rhythm. AB - BACKGROUND: Rheumatic fever and rheumatic heart disease remain important health problems in developing countries. Mitral stenosis (MS) is the most common form of rheumatic heart disease. The aim of this study was to investigate incidence and echocardiographic predictors of long-term adverse outcomes in patients with rheumatic mitral stenosis in sinus rhythm. MATERIAL AND METHOD: We retrospectively reviewed medical records of patients diagnosed with isolated rheumatic MS of any severity at Siriraj Hospital between 1996 and 2013. Demographic data, echocardiographic data, and long-term adverse outcomes were collected. Long-term adverse outcomes included all-cause mortality, hospitalization due to heart failure, new-onset atrial fibrillation, and/or embolic stroke during follow-up. RESULTS: One hundred eighty five patients (aged 41.9 +/- 13.2 years, 81.1% female) were included during the median follow-up period of 12.6 years (95% CI: 11.2-14.0). MS was classified as mild, moderate, and severe in 8.6%, 2 7.6%, and 63.8% of patients, respectively. Average mitral valve score was 8.25 +/- 1.5. Most patients (61.6%) underwent percutaneous balloon mitral valvulotomy. Incidence of long-term adverse outcome was 43.2% (95% CI: 36.0-50.7%) and included mortality in two patients (1.1%, 95% CI: 0.13-3.9%), hospitalization due to heart failure in 20 patients (10.8%, 95% CI: 6.7-16.2%), new-onset atrial fibrillation in 71 patients (38.4%, 95% CI: 31.3-45.8%), and embolic stroke in 14 patients (7.6%, 95% CI: 4.2-12.4%). Echocardiographic parameters associated with long-term adverse outcomes were left atrial dimension greater than 50 mm (HR 2.61, 95% CI: 1.08-6.30; p = 0.03) and left ventricular end-systolic dimension less than 28 mm (HR 3.06, 95% CI: 1.25-7.49; p = 0.01). CONCLUSION: Long-term adverse outcomes are common in patients with rheumatic MS in sinus rhythm. Long-term adverse outcomes were found to correlate with left atrial dimension and left ventricular end-systolic dimension. PMID- 27396221 TI - Prevalence and Outcome of Disseminated Varicella Zoster Infection Post Kidney Transplantation. AB - OBJECTIVE: Varicella zoster (VZV) is a potentially life-threatening infection after kidney transplantation (KT) but data on the incidence and outcome of late KT VZV infection is limited. MATERIAL AND METHOD: A retrospective study of disseminated VZV infection (D-VZV) in post KT patients was conducted between 2003 and 2013. Acyclovir prophylaxis was given routinely for six months after KT Statistical analyses were performed by SPSS software version 17.0. RESULTS: Prevalence of D-VZV was 2% [22/1,032 patients]. Patients median age were 40 (21 67) years old and 12 (55%) were male. Timing of the infection was mostly (68.2%) late (> 1 year) post KT The majority of maintenance immunosuppressive drug included prednisolone (95.5%), cyclosporine (77.3%), mycophenolate (68.2%). Two (9.1%) had a recent VZV exposure and four (18%) received intensified immunosuppression before the diagnosis. Common clinical presentations were lymphopenia (54.5%), generalized vesicular rash (50%), and multi-dermatomal distribution (50%) while liver involvement was infrequent (9.1%). None had pneumonitis or neurological involvement. All cases received systemic acyclovir with the median duration of 14 (3-31) days. One had received IVIG for fulminant hepatitis. Immunosuppressive drug/s was reduced in 59%. Median duration of hospitalization was seven (3-37) days. None of patients died. The median follow up duration was 1939 (IQR 804-2440) days. Recurrent infection was uncommon (4.5%). Secondary prophylaxis was given only in one patient with fulminant VZV hepatitis. CONCLUSION: Incidence of D-VZV post KT was low. Treatments with intravenous acyclovir and reduction of immunosuppression without the use of VZV IgG provided favorable outcome in resource-limited settings. PMID- 27396222 TI - The Relationship between Body Composition and Clinical Parameters in Chronic Obstructive Pulmonary Disease. AB - OBJECTIVE: Identify a correlation between body mass index (BMI) and fat-free mass index (FFMI) to clinical parameters in chronic obstructive pulmonary disease. MATERIAL AND METHOD: The cross-sectional study was conducted at a single visit involving stable chronic obstructive pulmonary disease (COPD) patients at the outpatient chest clinic of the Chiang Mai University Hospital, Thailand. Eligible patients were evaluated for BMI, FFMI, lung function, modified medical research council (mMRC) dyspnea score, COPD assessment test (CAT) score, and number of acute exacerbation (AE) in the past year. The correlations of FFMI and BMI with other parameters were determined using Pearson correlation coefficient analysis. Body composition was categorized into four groups, normal, semi-starvation, muscle atrophy/sarcopenia, and cachexia based on BMI and FFMI. Statistical significance was accepted at p-value < 0.05. RESULTS: One hundred twenty one stable COPD patients met study inclusion criteria. The FFMI showed a strong correlation with BMI (r = 0.792, p < 0.001). The FFMI, but not BMI, was significantly correlated with mMRC, precentage ofp redicted forced expiratory volume in first second (FEV1), and CAT score (r = -0.315, 0.214, and -0.278, respectively). Body composition was categorized into four groups: normal body composition (n = 62, 51.2%), semi-starvation (n = 4, 3.3%), sarcopenia/ muscular atrophy (n = 12, 9.9%), and cachexia (n = 43, 35.5%). CONCLUSION: FFMI, but not BMI, was significantly correlated with dyspnea severity, lung function, and quality of life. Body composition category assignment is a useful clinical tool. PMID- 27396223 TI - Accuracy of a New Stress Radiographic Device in Diagnosing Anterior Cruciate Ligament Tear. AB - BACKGROUND: Anterior cruciate ligament (A CL) tears are clinically diagnosed by detection of anterior tibial translation on physical examination; however, this manual method of assessment is imprecise, subjective, and not reproducible. Recently a new instrument, a stress radiographic device (SRD), was produced to objectively measure these displacements. OBJECTIVE: To assess a new instrument, a SRD, in the measurement of anterior tibial translation in ACL-deficient knee compared to the healthy ACL knee. MATERIAL AND METHOD: The SRD was applied to 24 ACL-tear knees that were diagnosed by MRI as having complete ACL tears,.and 24 healthy ACLs from the contralateral knee of each patient. Each knee was tested under a force 120 Newtons in a posterior to anterior direction to create anterior tibial translation at 20 degrees knee flexion. Side-to-side difference of anterior tibial translation (mm) was measured from radiographs. RESULTS: We studied 24 patients who had one knee with complete rupture of ACL diagnosed by MRI and the other with healthy ACL confirmed by clinical diagnosis. The mean anterior tibial translation before and after using the device was significantly lower in the healthy ACL group than in the ruptured ACL group. A stress radiographic device was used with a 4 mm side-to-side cut off point of difference of anterior tibial translation between pre- and post-stress displacement for diagnosis of complete rupture of anterior cruciate ligament. The sensitivity was 79% and specificity was 100%. CONCLUSION: The new stress radiographic device is reliable and reproducible in diagnosis of complete rupture of anterior cruciate ligament. PMID- 27396224 TI - Prophylactic Low-Dose Ketamine to Prevent Post Anesthetic Shivering in Orthopedic Surgery: A Randomized-Controlled Study. AB - OBJECTIVE: Post anesthetic shivering is one of the most common anesthesia complications. We compared the efficacy of low-dose ketamine with normal saline in preventing post anesthetic shivering in orthopedic surgery. MATERIAL AND METHOD: The present study was a prospective, randomized, double-blind, controlled clinical trial involving 183 ASA I-II patients, aged 18 to 65 years whom underwent orthopedic surgery with general anesthesia. The patients were randomly allocated to receive either ketamine 0.25 mg/kg (Group K, n = 91) or normal saline (Group P n = 92) 20 minutes before the completion of surgery. The tympanic temperature was measured before the induction of anesthesia, 30 minutes after induction, and before administration of the study drugs. An investigator, blinded to the patients' group affiliation, graded post anesthetic shivering using the Crossley and Mahajan scale. The primary outcome was to compare incidence of shivering on each group in recovery room. The secondary outcome was side effect of ketamine. Statistical analyses were performed using program R version 3.1.0. A p-value of < 0.05 was considered statistically significant. RESULTS: The patient characteristics of the two groups were similar and the number of patients with observed shivering in both groups was not statistically significantly different (Group K = 13 (14.28%) and Group P = 15 (16.30%), p = 0.42). Furthermore, in both groups, no patient suffered from hallucination, and the other complications were not statistically different. CONCLUSION: At the recovery room, no significant efficacy difference between low-dose ketamine (0.25 mg/kg) and placebo in the prevention of post operative shivering in patients who underwent orthopedic surgery was observed. Other factors such as preload warm intravenous fluid, using active warming during surgery and control of the room temperature may help prevent shivering. PMID- 27396225 TI - Epidemiology, Clinical Characteristics, Sites of Infection and Treatment Outcomes of Mucocutaneous Candidiasis Caused by Non-Albicans Species of Candida at a Dermatologic Clinic. AB - BACKGROUND: Increasing numbers of mucocutaneous infection due to non-albicans species of Candida (N-CA) had been reported. Laboratory based studies showed multidrug resistance in N-CA population. OBJECTIVE: Demonstrate epidemiology, clinical characteristics, sites of infection, and treatment outcomes of mucocutaneous candidiasis caused by N-CA at a dermatologic clinic, including statistical evaluation data between N-CA and C. albicans infections. MATERIAL AND METHOD: This was a cross sectional study of outpatients with mucocutaneous infection due to Candida at Dermatologic clinic between January 2012 and June 2014. Vaginal candidiasis was excluded. Demographic, clinical, laboratory data, and treatment outcomes were collected. RESULTS: Among 760 patients presented with mucocutaneous candidiasis, 307 (40.4%) were infected with N-CA. The mean age (SD) of N-CA patients was 63.6 (10.4) years and 74.6% were female. The majority of N CA cases were isolated from patients' nails (n = 293, 95.4%) while eight (2.6%) were detected from their skin, and six (2%)from oral mucosa. Comparison between N CA and C. albicans, skin, and mucosa infection were significantly demonstrated in C. albicans groups (p < 0.001). Among nail infected patients, C. albicans infections had significant higher severity than the N-CA infection (p = 0.017). Median time to cure in N-CA population was 169 days, which had no significant difference from C. albicans groups (211 days, p = 0.499). CONCLUSION: Forty percent of mucocutaneous candidiasis was caused by N-CA. Nails were the most common sites of N-CA infections but N-CA was sometime found in skin and mucosa. Treatment outcomes of N-CA population were not significantly different from those of C. albicans groups. PMID- 27396226 TI - Pathergy Test: The Comparison of Clinical vs. Histopathological Evaluation. AB - OBJECTIVE: Behcet's disease is an inflammatory disease of unknown etiology. Pathergy test is the only diagnostic test for Behcet's disease. The evaluation can be done either clinically and/or histopathologically. In the present study, we compare the sensitivity and specificity of clinical vs. histopathological evaluation of the pathergy test. MATERIAL AND METHOD: This was a retrospective study in patients who underwent pathergy tests at Phramongkutklao Hospital, Thailand between January 1, 2011 and December 31, 2013. Fifty-eight cases met the inclusion criteria and were included into the study. All basic demographic data were obtained from the medical records. The sensitivity, specificity, and accuracy of the test were evaluated. RESULTS: There were 33/58 (56.9%) cases with the final diagnosis as Behcet's disease. The sensitivity, specificity, and accuracy of the clinical evaluation of pathergy test were 30.3%, 64%, and 44.8% respectively. Upon using the histopathological evaluation, the sensitivity, specificity, and accuracy were 100%, 16%, and 63.8%, respectively. CONCLUSION: Our results showed that the histopathological evaluation of pathergy test helped to improve the accuracy and sensitivity, but the specificity was low. We suggest the use of histological evaluation of the pathergy test in cases where Behcet's disease is highly suspected especially in areas where the disease is uncommon. PMID- 27396227 TI - Prevalence of Cutaneous Bacterial Colonization in Thai Patients with Psoriasis. AB - OBJECTIVE: To determine bacterial colonization of skin, scalp, nares, nails, and psoriasis lesion in Thai psoriasis patients and compare findings with those of healthy controls. MATERIAL AND METHOD: Sixty patients with chronic plaque-type psoriasis and 60 healthy controls of similar age and gender were enrolled. Swabs of nares, scalp, nails, and non-lesional skin were taken from all subjects. Swabs of lesional skin were taken from psoriasis patients. Aerobic bacteria were isolated from swab specimens. RESULTS: Patients with psoriasis had significantly higher rate of bacteria colonization in nares, scalp, and nails than those of healthy controls. Firmicutes spp. was the most common phyla, followed by Proteobacteria spp. in both groups. Coagulase-negative staphylococci (CoNS) were the most common pathogens isolated from lesional skin, non-lesional skin, scalp, and nares of psoriasis patients. Streptococcus spp. was found only in psoriasis patients. CONCLUSION: Similar to findings from Caucasian psoriasis patients, Firmicutes spp. was found to be the most common phyla colonizing the skin of Asian psoriasis patients. Streptococcus spp. was found to colonize only the skin. Further studies are needed to determine the clinical significance of streptococcal skin colonization in psoriasis patients. PMID- 27396228 TI - The Outcome of Radiofrequency Ablation of Metastatic Liver Tumors. AB - OBJECTIVE: To determine outcome of radiofrequency ablation (RFA) in metastatic liver tumor and to evaluate related factors of residual or local tumor recurrences. MATERIAL AND METHOD: With Institutional Review Board approval, we retrospectively reviewed RFA procedure between June 2006 and September 2013. Fifty-seven metastatic nodules in 36 patients were treated. The primary tumors were colorectal carcinoma (n = 30), neuroendocrine tumor (n = 2), gallbladder carcinoma (n = 1), adenocarcinoma of head of pancreas (n = 1), and gastrointestinal stromal tumor (n = 2). Tumor characteristics, RFA techniques, success rate, complication, and follow-up imaging were reviewed and recorded Clinical outcome and overall survival were analyzed. RESULTS: Complete ablation were found in 48/57 nodules (84.2%). The mean follow-up time was 17.9 +/- 13.1 months (range, 1 to 47 months). Local tumor recurrence were noted in 12/57 nodules (21.1%), which mean time to recurrence was 8.3 +/- 3.8 months (2 to 15 months). Residual tumor was associate with tumor larger than 3 cm (p = 0.009). The 1-, 3-, and 5-year overall survival rates were 93.6%, 56.2%, and 20%, respectively. Median overall survival was 37.8 +/- 10.9 months. Major complication rate occurred about 5.3%. CONCLUSION: Radiofrequency ablation is effective and feasible method to treat small metastatic liver tumor Tumor size larger than 3 cm is significant risk factor of residual tumor. Tumor in high-risk location is not associated either incomplete ablation or local tumor recurrence. PMID- 27396229 TI - Cholinesterase Inhibitors and Behavioral & Psychological Symptoms of Alzheimer's Disease. AB - OBJECTIVE: Examine the effect of cholinesterase inhibitors (ChEIs) on behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), and compared the dosages of antipsychotics and SSRIs or SNRIs used to treat BPSD in patients with and without ChEIs. MATERIAL AND METHOD: The cross sectional study of Alzheimer patients who had been taking ChEls for at least six months (ChEI+) or had never been on any ChEIs (ChEI-) were enrolled from the Memory Clinic, Ramathibodi hospital between September 1, 2014 and February 28, 2015. All of these patients were evaluated with Mini-Mental Status Exam (MMSE) for cognitive function, Neuropsychiatric Inventory-Questionnaire (NPI-Q) for BPSD, and psychotropic dosage used. RESULTS: Fifty-one Alzheimer patients were enrolled, 31 patients in the ChEI+ group and 20 patients in the ChEI- group. Mean and SD of MMSEs in ChEI+ and ChEI- were 13.6 +/- 1.2 and 11.75 +/- 1.4, respectively (p-value = 0.33). The Mean and SD of NPI scores in ChEI+ and ChEI- were 15.68 +/- 14.31 and 19.5 +/- 20.1, respectively (p-value = 0.43). Patients in ChEI + had tend to had a lower depression severity score (p = 0.10) and lower burden from aggression/agitation (p = 0.08). The differences were not statistically signifcant. Mean highest dosages per day (olanzapine equivalence) in the ChEI+ and ChEI- were 1.6 mg and 3.1 mg, respectively (p-value = 0.07). CONCLUSION: The total off NPI score between the ChEI+ and ChEI- groups were not different, but there were report the trends toward lower depression severity score, aggression/agitation distress score, and antipsychotic dosages use in the ChEI+. PMID- 27396230 TI - Henoch-Schonlein without Purpura: A Case Report and Review Literature. AB - Henoch-Schonlein purpura (HSP) is a multi-organ vasculitis involving skin, joints, gastrointestinal tract, and kidneys. The present study reported a 5-year old boy presenting with intense abdominal pain, bloody diarrhea, and protein losing enteropathy. Investigations for infectious enteritis were negative. Esophagogastroduodenoscopy showed swelling and erythematous mucosa with hemorrhagic spots at duodenal bulb to the third part of duodenum. Histopathology of endoscopic biopsies revealed non-specific duodenitis. HSP was suspected, based on duodenitis and the presence of inflammatory markers without identifiable causes. Corticosteroid was started resulting in marked improvement of his clinical symptoms. Two weeks later, he developed nephrotic-range proteinuria, thus kidney biopsy was performed. Renal histology was consistent with IgA nephropathy, supporting the diagnosis of HSP This report emphasizes that patients with HSP may not always show visible purpura, and the diagnosis requires a high index of suspicion. GI endoscopy and renal biopsy may be helpful for the diagnosis in selected patients presenting with atypical presentations. PMID- 27396231 TI - The Effect of English Language on Multiple Choice Question Scores of Thai Medical Students. AB - BACKGROUND: Universities in Thailand are preparing for Thailand's integration into the ASEAN Economic Community (AEC) by increasing the number of tests in English language. English language is not the native language of Thailand Differences in English language proficiency may affect scores among test-takers, even when subject knowledge among test-takers is comparable and may falsely represent the knowledge level of the test-taker. OBJECTIVE: To study the impact of English language multiple choice test questions on test scores of medical students. MATERIAL AND METHOD: The final examination of fourth-year medical students completing internal medicine rotation contains 120 multiple choice questions (MCQ). The languages used on the test are Thai and English at a ratio of 3:1. Individual scores of tests taken in both languages were collected and the effect of English language on MCQ was analyzed Individual MCQ scores were then compared with individual student English language proficiency and student grade point average (GPA). RESULTS: Two hundred ninety five fourth-year medical students were enrolled. The mean percentage of MCQ scores in Thai and English were significantly different (65.0 +/- 8.4 and 56.5 +/- 12.4, respectively, p < 0.001). The correlation between MCQ scores in Thai and English was fair (Spearman's correlation coefficient = 0.41, p < 0.001). Of 295 students, only 73 (24.7%) students scored higher when being tested in English than in Thai language. Students were classified into six grade categories (A, B+, B, C+, C, and D+), which cumulatively measured total internal medicine rotation performance score plus final examination score. MCQ scores from Thai language examination were more closely correlated with total course grades than were the scores from English language examination (Spearman's correlation coefficient = 0.73 (p < 0.001) and 0.53 (p < 0.001), respectively). The gap difference between MCQ scores in both languages was higher in borderline students than in the excellent student group (11.2 +/- 11.2 and 7.1 +/- 8.2, respectively, p < 0.001). Overall, average student English proficiency score was very high, at 3.71 +/- 0.35 from a total of 4.00. Mean student GPA was 3.40 +/- 0.33 from a possible 4.00. English language MCQ examination scores were more highly associated with GPA than with English language proficiency. CONCLUSION: The use of English language multiple choice question test may decrease scores of the fourth-year internal medicine post rotation final examination, especially those of borderline students. PMID- 27396232 TI - [The importance of human response and collaboration problems in radioactive iodine treatment]. PMID- 27396233 TI - The cementless fibre mesh coated anatomic femoral stem: 12 to 23 years clinical and radiological outcome study. AB - INTRODUCTION: The aim of this study was to assess the long-term clinical and radiographic results, and possible reasons for failure of two versions of the cementless fibre-metal coated anatomical femoral component. METHODS: 99 patients (119 hips) were evaluated at an average of 16.7 years (range, 12 to 23 years) following primary THA. Developmental dysplasia of the hip (DDH) was the most common pathology (n = 37 hips). Structural femoral head autografts were used to increase cup coverage in 23 hips. Vertical and horizontal migration of acetabular and femoral components and osteolysis around the components were assessed using conventional radiolography. For clinical evaluation, the Harris Hip Score and Merle D'Aubigne scale were used preoperatively and at final follow up. Implant survival was calculated according to the Kaplan-Meier survivorship analysis and failure was defined as component's revision for any reason. RESULTS: The cumulative survival rate of the anatomical femoral stem was 64.2% at 19.8 years, with a worst-case scenario of 41%. The cumulative survival rate of the total hip arthroplasty was 51% at 19.8 years, with a worse case scenario of 38%. The mean preoperative Harris Hip Score of 42 points improved to 88 postoperatively. The mean preoperative Merle D'Aubigne functional score of 3.5 improved to 5.2 points at the time of final follow-up. In 36 hips (41.6%) osteolysis was found in Gruen zone 1, proximal to the ingrowth surface. CONCLUSIONS: The cementless fibre-metal coated anatomical femoral component showed favourable long-term clinical and radiological results. Proximal coating seems to protect bone implant interface from wear debris induced osteolysis during the second decade. PMID- 27396234 TI - Observation of interaction-induced modulations of a quantum Hall liquid's area. AB - Studies of electronic interferometers, based on edge-channel transport in the quantum Hall effect regime, have been stimulated by the search for evidence of abelian and non-abelian anyonic statistics of fractional charges. In particular, the electronic Fabry-Perot interferometer has been found to be Coulomb dominated, thus masking coherent Aharonov-Bohm interference patterns: the flux trapped within the interferometer remains unchanged as the applied magnetic field is varied, barring unobservable modulations of the interference area. Here we report on conductance measurements indicative of the interferometer's area 'breathing' with the variation of the magnetic field, associated with observable (a fraction of a flux quantum) variations of the trapped flux. This is the result of partial (controlled) screening of Coulomb interactions. Our results introduce a novel experimental tool for probing anyonic statistics. PMID- 27396235 TI - IJBNPA in 2016: Strategy for advancing the science of behavior change in nutrition and physical activity, and associated editorial priorities. AB - The goal of the International Journal of Behavioral Nutrition and Physical Activity (IJBNPA) is to be the leading diet and physical activity journal. To achieve this aim we embrace and publish a number of different research designs from small, but in depth, qualitative studies to large scale cohort studies. IJBNPA prioritises research based on randomised controlled trials (RCTs), systematic reviews (with or without meta-analyses, as appropriate), and well conducted observational studies that expand knowledge and understanding of the area. IJBNPA will also consider and publish other study designs that are of sufficient quality such as strong or ground-breaking methodological papers, rigorous qualitative studies, debate papers and commentaries. However, due to the demands on the journal, we publish pilot studies only in exceptional circumstances and we do not publish protocol papers or letters to the editors. The goal of this editorial is to highlight to our readers and authors the process by which we identify which papers to review and publish along with our editorial priorities. PMID- 27396236 TI - Non-thermal plasma prevents progression of endometriosis in mice. AB - Endometriosis is observed in ~10% of reproductive age women. Ovarian endometriosis not only causes dysmenorrhea but also causes infertility and a high risk of adenocarcinoma. Due to its scattered nature, complete surgical resection is difficult. Endometriosis consists of glandular and stromal cells. Previously, we showed that endometrial stromal cells (ESCs) play a role in the protection against pathologic events caused by monthly repeated hemorrhage. Here, we undertook a preclinical study of non-thermal plasma (NTP) as a surgical treatment of endometriosis. Epithelial cells were most sensitive to NTP-activated medium in vitro, whereas ectopic ESCs were most resistant. We then transplanted excised uteruses into BALB/c mice from donors of the same strain with estradiol supplementation. Four weeks after the transplantation, we exposed NTP to each endometriotic lesion after laparotomy. Immunohistochemical analysis revealed that immediately after NTP exposure, epithelial cells exhibited significantly higher levels of nuclear immunostaining for 8-hydroxy-2'-deoxyguanosine than did stromal cells. Four weeks after NTP exposure, the total surface area consisting of endometriotic cysts was significantly smaller with less epithelial proliferative activity than the helium-exposed control, whereas the number of endometriotic lesions had not changed. Therefore, NTP exposure may be useful to prevent the progression and recurrence of endometriosis. PMID- 27396237 TI - Prevalence and predictors of bias in the reporting of primary efficacy and toxicity endpoints in randomized clinical trials of radiation oncology. AB - INTRODUCTION: To determine the prevalence and predictors of bias in reporting of primary efficacy and toxicity endpoints in randomized trials (RCTs) of radiation oncology. METHODS: We searched MEDLINE for eligible RCTs published from January 1994 to October 2014. Bias in reporting of primary efficacy endpoint was defined as reporting that treatment was beneficial based on secondary endpoints despite a statistically non-significant difference in primary endpoint. Bias in reporting of toxicity endpoint was defined as not reporting toxicity findings in the abstract, discussion or results table. Logistic regression multivariate models were used to determine predictors of biased reporting. RESULTS: We found that 13% of 323 RCTs have bias in the reporting of primary efficacy endpoint with non cooperative group trials as a significant predictor of bias (odds ratio (OR) 2.04, 95% confidence interval (CI) 1.03-4.00, P = 0.04). Thirty-five per cent of 279 RCTs were judged to have bias in the reporting of toxicity endpoint with trials not listed in Clinicaltrials.gov as a significant predictor of bias (OR 3.23, 95% CI 1.43-7.14, P = 0.004). CONCLUSION: The prevalence of bias in reporting of primary efficacy and toxicity endpoint for radiotherapy RCTs was 13% and 35% respectively. Non-cooperative group trials were more likely to have bias in the reporting of primary efficacy endpoint. Trials not listed in Clinicaltrials.gov were more likely to have bias in the reporting of toxicity endpoint. PMID- 27396238 TI - Finding needles in a genomic haystack: targeted capture identifies clear signatures of selection in a nonmodel plant species. AB - Teasing apart neutral and adaptive genomic processes and identifying loci that are targets of selection can be difficult, particularly for nonmodel species that lack a reference genome. However, identifying such loci and the factors driving selection have the potential to greatly assist conservation and restoration practices, especially for the management of species in the face of contemporary and future climate change. Here, we focus on assessing adaptive genomic variation within a nonmodel plant species, the narrow-leaf hopbush (Dodonaea viscosa ssp. angustissima), commonly used for restoration in Australia. We used a hybrid capture target enrichment approach to selectively sequence 970 genes across 17 populations along a latitudinal gradient from 30 degrees S to 36 degrees S. We analysed 8462 single-nucleotide polymorphisms (SNPs) for FST outliers as well as associations with environmental variables. Using three different methods, we found 55 SNPs with significant correlations to temperature and water availability, and 38 SNPs to elevation. Genes containing SNPs identified as under environmental selection were diverse, including aquaporin and abscisic acid genes, as well as genes with ontologies relating to responses to environmental stressors such as water deprivation and salt stress. Redundancy analysis demonstrated that only a small proportion of the total genetic variance was explained by environmental variables. We demonstrate that selection has led to clines in allele frequencies in a number of functional genes, including those linked to leaf shape and stomatal variation, which have been previously observed to vary along the sampled environmental cline. Using our approach, gene regions subject to environmental selection can be readily identified for nonmodel organisms. PMID- 27396239 TI - Posture-induced changes in peripheral nerve stiffness measured by ultrasound shear-wave elastography. AB - INTRODUCTION: Peripheral nerves slide and stretch during limb movements. Changes in nerve stiffness associated with such movements have not been examined in detail but may be important in understanding movement-evoked pain in patients with a variety of different musculoskeletal conditions. METHODS: Shear-wave elastography was used to examine stiffness in the median and tibial nerves of healthy individuals during postures used clinically to stretch these nerves. RESULTS: Shear-wave velocity increased when limbs were moved into postures that are thought to increase nerve stiffness (mean increase: median nerve = 208% in arm, 236% in forearm; tibial nerve = 136%). There was a trend toward a negative correlation between age and shear-wave velocity (r = 0.58 for tibial nerve). CONCLUSIONS: Shear-wave elastography provides a tool for examining nerve biomechanics in healthy individuals and patients. However, limb position, age, and effects of nerve tension on neural architecture should be taken into consideration. Muscle Nerve 55: 213-222, 2017. PMID- 27396240 TI - Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complications Study. AB - AIMS: The Japan Diabetes Complications Study (JDCS), a nation-wide, multicenter, prospective study of patients with type 2 diabetes, reported that hemoglobin A1c (HbA1c), systolic blood pressure, and smoking were risk factors for the onset of macroalbuminuria. This study explored the risk factors for glomerular filtration rate (GFR) decline in the JDCS patients. METHODS: We examined the 1407 JDCS patients (667 women, mean age 59years, 974 normoalbuminuria, 433 microalbuminuria) whose urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) were determined at baseline with an 8-year follow-up. We divided all the patients into four groups according to baseline eGFR: G1 (120<=eGFR), G2 (90<=eGFR<120), G3 (60<=eGFR<90), G4 (eGFR<60). RESULTS: The eGFRs in groups G1 and G2 decreased at follow-up compared to those at the baseline. The risk of annual eGFR decline rate>=3ml/min/1.73m2 (rapid decliners) increased as the baseline eGFR increased. Advanced age, high HbA1c, and UACR, or diabetic retinopathy at baseline were risk factors for the rapid decliners. Especially the G1 group had a significant risk for the rapid decliners. The frequency of the patients with GFR<60ml/min/1.73m2 at the follow-up amounted to 31.1% in the rapid decliners, which was higher than 12% in the non-rapid decliners. CONCLUSIONS: In normo- and microalbuminuric patients with type 2 diabetes, extra careful attention should be paid to patients with eGFR >=120ml/min/1.73m2 to detect cases with rapidly decreased GFR under the normal range. PMID- 27396241 TI - Safety and efficacy of linagliptin in patients with type 2 diabetes mellitus and coronary artery disease: Analysis of pooled events from 19 clinical trials. AB - AIMS: To examine the safety and efficacy of linagliptin in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) using pooled data from the global clinical trials program. METHODS: Patient-level data were pooled from randomized, placebo-controlled clinical trials of linagliptin (5mg, monotherapy or combination therapy). Safety/efficacy analyses were conducted for patients with CAD and >=12 and >=24weeks of treatment, respectively. RESULTS: The safety analysis included 19 trials (linagliptin, n=451; placebo, n=272) and the efficacy analysis, 12 trials (linagliptin, n=328; placebo, n=198); mean (+/- standard deviation) exposure to study treatment was 212 (144) days linagliptin and 245 (171) days placebo. Occurrence of cardiac adverse events (AEs) was similar for linagliptin- and placebo-treated patients (9.1% and 9.2%, respectively); exposure adjusted incidence rates (per 100 patient-years) were 16.6 and 14.0, respectively. Overall incidence of AEs was numerically lower with linagliptin than placebo. After 24weeks, mean adjusted change (standard error) from baseline glycosylated hemoglobin was -0.64% (0.04) with linagliptin vs. -0.08% (0.05) with placebo (P<.001). CONCLUSIONS: This comprehensive pooled analysis showed that addition of linagliptin to treatment regimens of patients with T2DM and CAD was not associated with an increased incidence of cardiac AEs, was well tolerated, and was effective. PMID- 27396243 TI - Mechanically robust 39 GHz cut-off frequency graphene field effect transistors on flexible substrates. AB - Graphene has been regarded as a promising candidate channel material for flexible devices operating at radio-frequency (RF). In this work we fabricated and fully characterized double bottom-gate graphene field effect transistors on flexible polymer substrates for high frequency applications. We report a record high as measured current gain cut-off frequency (ft) of 39 GHz. The corresponding maximum oscillation frequency (fmax) is 13.5 GHz. These state of the art high frequency performances are stable against bending, with a typical variation of around 10%, for a bending radius of up to 12 mm. To demonstrate the reliability of our devices, we performed a fatigue stress test for RF-GFETs which were dynamically bend tested 1000 times at 1 Hz. The devices are mechanically robust, and performances are stable with typical variations of 15%. Finally we investigate thermal dissipation, which is a critical parameter for flexible electronics. We show that at the optimum polarization the normalized power dissipated by the GFETs is about 0.35 mW MUm(-2) and that the substrate temperature is around 200 degree centigrade. At a higher power, irreversible degradations of the performances are observed. Our study on state of the art flexible GFETs demonstrates mechanical robustness and stability upon heating, two important elements to assess the potential of GFETs for flexible electronics. PMID- 27396242 TI - Effects of thrombin on insulin signalling and glucose uptake in cultured human myotubes. AB - BACKGROUND: Hyper-coagulability (elevated thrombin) is a feature of type 2 diabetes and contributes to an increased risk of thrombotic and vascular events. Skeletal muscle is the key peripheral tissue site of insulin resistance in type 2 diabetes. Cultured human skeletal muscle cells were used to explore the effects of thrombin on insulin signalling and glucose uptake. We hypothesized that thrombin affects insulin activity in human skeletal muscle cells which could link the hypercoagulability and insulin resistance in type 2 diabetes. METHODS: Human skeletal muscle cell cultures (myotubes) were treated with +/-5 units/ml thrombin for 6h. Insulin signalling pathway components and AMPK were examined by Western blotting. Real time PCR and glucose uptake assays were performed. RESULTS: There was a significant decrease (p<0.01) in insulin mediated IRS-1 and Akt phosphorylation in response to thrombin in cultured myotubes. Diminished Akt phosphorylation was alleviated by treatment with a PKC inhibitor. Thrombin directly increased basal glucose uptake (p<0.05) that involved AMPK phosphorylation (p<0.01) and this was partly repressed by compound C (AMPK inhibitor). Thrombin also significantly increased the gene expression level of both GLUT1 and GLUT4 in cultured human skeletal muscle cells. CONCLUSION: Thrombin decreased insulin signalling in skeletal muscle cells through a PKC mediated mechanism, but did not affect the net action of insulin on glucose uptake. The direct stimulatory effect of thrombin on glucose uptake was mediated, at least in part, via an AMPK dependent mechanism. We conclude that thrombin activation results in multiple metabolic effects beyond increased thrombogenicity but does not include a decrease in insulin sensitivity (glucose uptake) in cultured human skeletal muscle cells. PMID- 27396244 TI - Intra-Aortic Balloon Pump Counterpulsation in the Post-Resuscitation Period is Associated with Improved Functional Outcomes in Patients Surviving an Out-of Hospital Cardiac Arrest: Insights from a Dedicated Heart Attack Centre. AB - BACKGROUND: Despite advances in cardiopulmonary resuscitation, functional survival remains low after out-of-hospital cardiac arrest (OOHCA). Intra-aortic balloon pump (IABP) therapy has recently been shown to augment cerebral blood flow. Whether IABP therapy in the post-resuscitation period improves functional outcomes is unknown. METHODS: We analysed 174 consecutive patients who were successfully resuscitated from an OOHCA between 2011-2013 at Harefield Hospital, London. We analysed functional status at discharge and mortality up to one year. RESULTS: A total of 55 patients (32.1%) received IABP therapy. Comparing those receiving IABP with those not receiving IABP, there was no difference in favourable functional status at discharge (49.1% vs. 57.1%, p=0.321); and mortality at one year (45.5% vs. 35.5%, p=0.164). Multivariable analyses identified IABP therapy as a strong independent predictor for favourable functional status at discharge (OR=7.51, 95% CI: 2.15-26.14, p=0.002) and this association was maintained in propensity-score adjusted analyses (OR=9.90, 95% CI: 2.11-46.33, p=0.004) and inverse probability treatment weighted analyses (OR=10.84, 95% CI: 2.75-42.69, p<0.001). However, IABP therapy was not an independent predictor for mortality at one year (HR=0.93, 95% CI: 0.52-1.65, p=0.810) and this was confirmed in both propensity-score adjusted and inverse probability treatment weighted analyses. CONCLUSIONS: In this observational analysis of patients surviving an OOHCA, the use of IABP therapy in the post resuscitation period was associated with improved functional outcomes. This warrants further evaluation in larger prospective studies. PMID- 27396245 TI - Cadaveric training - the solution for ultrasound-guided regional anaesthesia? PMID- 27396246 TI - Pensions, tax and the anaesthetist: significant implications for workforce planning. AB - This paper shows how recent tax changes to pensions (i.e. new lifetime and annual allowance contribution limits) mean that NHS consultants will need to adopt one of four rational strategies to work and financial planning. Two of those strategies (termed 'Earn Fast, Drop Out' and 'Never Enter') involve a break between work and pensions. The logical consequence of this break is that consultants may exercise options to maximise their total income, which in turn will result in less work within the NHS and more work in alternative higher paying (e.g. private) sectors. A third strategy ('Go Slow, Stay Low') also involves less-than-full-time NHS work. Only one option ('Do Nothing' as a result of the tax changes) has no effect. In short, the tax changes will predictably lead to future senior consultants devoting proportionately much less of their time to NHS work than before. The article discusses the important implications of this conclusion for NHS workforce planning. PMID- 27396247 TI - A randomised placebo-controlled trial examining the effect on hand supination after the addition of a suprascapular nerve block to infraclavicular brachial plexus blockade. AB - Some surgeons believe that infraclavicular brachial plexus blocks tends to result in supination of the hand/forearm, which may make surgical access to the dorsum of the hand more difficult. We hypothesised that this supination may be reduced by the addition of a suprascapular nerve block. In a double-blind, randomised, placebo-controlled study, our primary outcome measure was the amount of supination (as assessed by wrist angulation) 30 min after infraclavicular brachial plexus block, with (suprascapular group) or without (control group) a supplementary suprascapular block. All blocks were ultrasound-guided. The secondary outcome measure was an assessment by the surgeon of the intra-operative position of the hand. Considering only patients with successful nerve blocks, mean (SD) wrist angulation was lower (33 (27) vs. 61 (44) degrees; p = 0.018) and assessment of the hand position was better (11/11 vs. 6/11 rated as 'good'; p = 0.04) in the suprascapular group. The addition of a suprascapular nerve block to an infraclavicular brachial plexus block can provide a better hand/forearm position for dorsal hand surgery. PMID- 27396248 TI - Identifying workflow disruptions in the cardiovascular operating room. AB - The objectives of this study were to identify the frequency and nature of flow disruptions in the operating room with respect to three cardiac surgical team members: anaesthetists; circulating nurses; and perfusionists. Data collected from 15 cases and coded using a human factors taxonomy identified 878 disruptions. Significant differences were identified in frequency relative to discipline type. Circulating nurses experienced more coordination disruptions (chi(2) (2, N = 110) = 7.136, p < 0.028) and interruptions (chi(2) (2, N = 427) = 29.743, p = 0.001) than anaesthetists and perfusionists, whereas anaesthetists and perfusionists experienced more layout issues than circulating nurses (chi(2) (2, N = 153) = 48.558, p = 0.001). Time to resolve disruptions also varied among disciplines (lambda (12, 878) = 5.186, p = 0.000). Although most investigations take a one-size fits all approach in addressing disruptions to flow, this study demonstrates that targeted interventions must focus on differences with respect to individual role. PMID- 27396249 TI - Risk of bias and methodological appraisal practices in systematic reviews published in anaesthetic journals: a meta-epidemiological study. AB - The validity of primary study results included in systematic reviews plays an important role in drawing conclusions about intervention effectiveness and carries implications for clinical decision-making. We evaluated the prevalence of methodological quality and risk of bias assessments in systematic reviews published in the five highest-ranked anaesthesia journals since 2007. The initial PubMed search yielded 315 citations, and our final sample after screening consisted of 207 systematic reviews. One hundred and seventy-four reviews conducted methodological quality/risk of bias analyses. The Jadad scale was most frequently used. Forty-four of the 83 reviews that included high risk of bias studies re-analysed their data omitting these trials: 20 showed differences in pooled effect estimates. Reviews containing a greater number of primary studies evaluated quality less frequently than smaller reviews. Overall, the majority of reviews evaluated bias; however, many applied questionable methods. Given the potential effects of bias on summary outcomes, greater attention is warranted. PMID- 27396251 TI - The 'Bath Boarding Card': a novel tool for improving pre-operative care for emergency laparotomy patients. PMID- 27396252 TI - Do I need ethics for this? PMID- 27396253 TI - Nomograms for calculating drug doses in obese adults. PMID- 27396254 TI - Abandoning first generation supraglottic airway devices. PMID- 27396255 TI - Abandoning use of 1(st) generation SAD - a reply. PMID- 27396256 TI - Neuromuscular monitoring and the AAGBI 2016 monitoring guidelines. PMID- 27396257 TI - Plasma cholinesterase deficiency in Turkish patients - a reply. PMID- 27396258 TI - Plasma cholinesterase deficiency in Turkish patients. PMID- 27396259 TI - Perineural or intravenous dexamethasone: do we still need catheters? PMID- 27396261 TI - AAGBI Safe vascular access guidelines I. PMID- 27396260 TI - Waveform analysis for lumbar epidural needle placement in labour. PMID- 27396262 TI - AAGBI safe vascular access guidelines II. PMID- 27396263 TI - Propofol infusion in children. PMID- 27396264 TI - Confusion about sedation. PMID- 27396265 TI - Propofol infusion in children - a reply. PMID- 27396266 TI - Hyaluronic acid fillers and hyaluronidase use in regional eye blocks. PMID- 27396267 TI - Microstructural Control via Copious Nucleation Manipulated by In Situ Formed Nucleants: Large-Sized and Ductile Metallic Glass Composites. AB - A novel strategy to control the precipitation behavior of the austenitic phase, and to obtain large-sized, transformation-induced, plasticity-reinforced bulk metallic glass matrix composites, with good tensile properties, is proposed. By inducing heterogeneous nucleation of the transformable reinforcement via potent nucleants formed in situ, the characteristics of the austenitic phase are well manipulated. PMID- 27396268 TI - Timely initiation of chemotherapy: a systematic literature review of six priority cancers - results and recommendations for clinical practice. AB - This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided. PMID- 27396269 TI - Laser-activated transforming growth factor-beta1 induces human beta-defensin 2: implications for laser therapies for periodontitis and peri-implantitis. AB - BACKGROUND: There is increasing popularity of high-power lasers for surgical debridement and antimicrobial therapy in the management of peri-implantitis and periodontal therapy. Removal of the noxious foci would naturally promote tissue healing directly. However, there are also anecdotal reports of better healing around routine high-power laser procedures. The precise mechanisms mediating these effects remain to be fully elucidated. This work examines these low-dose laser bystander effects on oral human epithelial and fibroblasts, particularly focusing on the role of human beta-defensin 2 (HBD-2 or DEFB4A), a potent factor capable of antimicrobial effects and promoting wound healing. MATERIAL AND METHODS: Laser treatments were performed using a near-infrared laser (810 nm diode) at low doses. Normal human oral keratinocytes and fibroblast cells were used and HBD-2 mRNA and protein expression was assessed with real time polymerase chain reaction, western blotting and immunostaining. Role of transforming growth factor (TGF)-beta1 signaling in this process was dissected using pathway-specific small molecule inhibitors. RESULTS: We observed laser treatments robustly induced HBD-2 expression in an oral fibroblast cell line compared to a keratinocyte cell line. Low-dose laser treatments results in activation of the TGF-beta1 pathway that mediated HBD-2 expression. The two arms of TGF-beta1 signaling, Smad and non Smad are involved in laser-mediated HBD-2 expression. CONCLUSIONS: Laser activated TGF-beta1 signaling and induced expression of HBD-2, both of which are individually capable of promoting healing in tissues adjacent to high-power surgical laser applications. Moreover, the use of low-dose laser therapy itself can provide additional therapeutic benefits for effective clinical management of periodontal or peri-implant disease. PMID- 27396270 TI - Evaluation of exposure of pemphigus vulgaris patients to Mycobacterium tuberculosis and Aspergillus fumigatus. AB - The purpose of this study was to screen pemphigus vulgaris (PV) (autoimmune bullous skin disease) for the presence of immunoglobulin G against Mycobacterium tuberculosis and Aspergillus fumigatus. The sera of 60 PV patients and 28 controls were screened for the presence of immunoglobulin G against M. tuberculosis and A. fumigatus by enzyme-linked immune-sorbent assay. Forty patients were females and 20 were males. The range of IgG against M. tuberculosis was from 0.9 to 152.6 (median = 2.95) in the patients and was from 0 to 2.2 (median = 1.6) in the controls. Seven (11.7 %) patients and none of the controls exceeded the cut-off value. Four patients were on systemic steroids and azathioprine and three did not receive treatment before. The results showed that PV patients had significantly more IgG against M. tuberculosis than the controls; the p value was 0.006. The range of IgG against A. fumigatus was from 1.3 to 76.3 (median = 4.9) in the patients and was from 1 to 105.3 (median = 5.25) in the controls. Six (10 %) patients and eight (28.6 %) controls exceeded the cut-off value. The six patients were on systemic steroids and azathioprine. No significant difference was detected between PV patients and controls regarding exposure to A. fumigatus; the p value was 0.308. PV patients showed significantly more exposure to the M. tuberculosis than the controls. This suggests that M. tuberculosis may contribute to the pathogenesis of PV. PMID- 27396272 TI - Congenital lateral abdominal wall hernia. AB - Congenital abdominal wall defects that are located outside of the anterior wall are extremely rare and difficult to classify because there are no well accepted guidelines. There are two regions outside of the anterior wall: the flank or lateral wall; and the lumbar region. We report the case of a patient with an oval 3 cm-diameter hernia defect located above the anterior axillary line, which affects all layers of the muscular wall. An anorectal malformation consisting of a recto-vestibular fistula was also identified, and chest X-ray showed dextrocardia. The suggested treatment is repair of the defect before 1 year of age. Given that the anomalies described may accompany lateral abdominal wall hernia, it is important to diagnose and treat the associated defects. PMID- 27396273 TI - Magnetic and thermoelectric properties of the ternary pseudo-hollandite BaxCr5Se8 (0.5 < x < 0.55) solid solution. AB - The structure of Ba0.5Cr5Se8 has been recently resolved, and its thermoelectric and magnetic properties have been studied. A ZT of 0.12 was found at around 800 K. Here, we report a study on the pseudo-hollandite BaxCr5Se8 solid-solution with 0.5 <= x <= 0.55 and its thermoelectric and magnetic properties. There is no significant impact either on the cell parameters depending on the cation content or on the magnetic properties. However, thermoelectric properties are radically changed depending on x content. While the low thermal conductivity, around 0.8 W m(-1) K(-1), remains similar for all samples, a respective increase and decrease of the resistivity and the Seebeck coefficient are observed with increasing Ba content. The maximum Seebeck coefficient is found with Ba0.5Cr5Se8 at around 635 K with 315 MUV K(-1), and the Seebeck coefficient then decreases and is correlated with an activation of minority charge carriers confirmed by Hall measurements. A similar but steeper behavior is observed for the Ba0.55Cr5Se8 temperature dependence plot at around 573 K. Finally, the best thermoelectric performances are found using the lowest content of Ba, unlike when x tends to 0.55, ZT approaches a tenth of the initial best value. BaxCr5Se8 compounds are antiferromagnetic with TN = 58 K. A large peak in thermal conductivity is observed around the antiferromagnetic transition for all stoichiometry. PMID- 27396275 TI - Coming in Postgraduate Medicine. PMID- 27396274 TI - Autoimmune Post-Herpes Simplex Encephalitis. AB - Investigators at August Pi Sunyer Biomedical Research Institute and University of Barcelona performed a prospective surveillance study in 14 patients with immune mediating relapsing symptoms of post-herpes simplex encephalitis (HSE). PMID- 27396277 TI - Problems/Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27396278 TI - Meetings and Courses. PMID- 27396279 TI - What's Happening in Medicine! PMID- 27396271 TI - Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view. AB - Ras proteins are small GTPases, cycling between inactive GDP-bound and active GTP bound states. Through these switches they regulate signaling that controls cell growth and proliferation. Activating Ras mutations are associated with approximately 30% of human cancers, which are frequently resistant to standard therapies. Over the past few years, structural biology and in silico drug design, coupled with improved screening technology, led to a handful of promising inhibitors, raising the possibility of drugging Ras proteins. At the same time, the invariable emergence of drug resistance argues for the critical importance of additionally honing in on signaling pathways which are likely to be involved. Here we overview current advances in Ras structural knowledge, including the conformational dynamic of full-length Ras in solution and at the membrane, therapeutic inhibition of Ras activity by targeting its active site, allosteric sites, and Ras-effector protein-protein interfaces, Ras dimers, the K Ras4B/calmodulin/PI3Kalpha trimer, and targeting Ras with siRNA. To mitigate drug resistance, we propose signaling pathways that can be co-targeted along with Ras and explain why. These include pathways leading to the expression (or activation) of YAP1 and c-Myc. We postulate that these and Ras signaling pathways, MAPK/ERK and PI3K/Akt/mTOR, act independently and in corresponding ways in cell cycle control. The structural data are instrumental in the discovery and development of Ras inhibitors for treating RAS-driven cancers. Together with the signaling blueprints through which drug resistance can evolve, this review provides a comprehensive and innovative master plan for tackling mutant Ras proteins. PMID- 27396280 TI - Washington Report on Health. PMID- 27396281 TI - Advances in Prosthetic and Assistive Devices. PMID- 27396282 TI - Medical Ethics: From Physician's Office to University Classroom. PMID- 27396284 TI - Personal business. PMID- 27396285 TI - The Medical Muse. PMID- 27396288 TI - Rapid Covalent Modification of Silicon Oxide Surfaces through Microwave-Assisted Reactions with Alcohols. AB - We demonstrate the method of a rapid covalent modification of silicon oxide surfaces with alcohol-containing compounds with assistance by microwave reactions. Alcohol-containing compounds are prevalent reagents in the laboratory, which are also relatively easy to handle because of their stability against exposure to atmospheric moisture. The condensation of these alcohols with the surfaces of silicon oxides is often hindered by slow reaction kinetics. Microwave radiation effectively accelerates this condensation reaction by heating the substrates and/or solvents. A variety of substrates were modified in this demonstration, such as silicon oxide films of various thicknesses, glass substrates such as microscope slides (soda lime), and quartz. The monolayers prepared through this strategy demonstrated the successful formation of covalent surface modifications of silicon oxides with water contact angles of up to 110 degrees and typical hysteresis values of 2 degrees or less. An evaluation of the hydrolytic stability of these monolayers demonstrated their excellent stability under acidic conditions. The techniques introduced in this article were successfully applied to tune the surface chemistry of silicon oxides to achieve hydrophobic, oleophobic, and/or charged surfaces. PMID- 27396287 TI - Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete). AB - BACKGROUND & AIMS: Vitamin D deficiency is common among pregnant women and may be associated with several adverse health outcomes including cancer. Micronuclei frequency is a biomarker of early genetic effects and has been used to examine the association between genotoxic exposures and cancer. We examined maternal vitamin D levels during pregnancy in associations with micronuclei frequency in maternal blood and in cord blood. METHODS: 173 mothers and 171 newborns born between 2007 and 2008 in Heraklion (Crete, Greece) were included in the study. Between 14th and 18th weeks of gestation we collected information on maternal diet using food frequency questionnaires (FFQs). We measured maternal serum concentrations of 25-hydroxyvitamin D [25(OH)D] between the first and second trimester of pregnancy. We estimated dietary vitamin D intake using information from FFQ. After delivery we collected cord blood and maternal peripheral blood. We used the cytokinesis-block micronucleus (CBMN) assay to assess the frequencies of micronucleated cells in binucleated T lymphocytes (MNBN). RESULTS: Maternal insufficient serum levels of 25(OH)D (<50 nmol/L) during pregnancy were associated with increased MNBN frequency in cord blood [IRR = 1.32 (95%CI: 1.00, 1.72)]. This increase was higher for newborns with birth weight above the third quartile [>=3.500 kg; IRR = 2.21 (1.26, 3.89)]. Similarly, low levels of dietary vitamin D were associated with increased MNBN frequency in cord blood [middle tertile IRR = 1.08 (0.78, 1.47), lower tertile IRR = 1.51 (1.06, 2.14)]. Insufficient levels of vitamin D were not associated with MNBN in mothers. CONCLUSION: Our results suggest that vitamin D deficiency during pregnancy increases genotoxic risks in newborns. The prevalence of vitamin D deficiency globally is high and it is important to further investigate whether vitamin D supplementation or similar interventions during pregnancy could prevent DNA damage at early stages of life. PMID- 27396290 TI - Why do we persist in using pediatric fall risk scales that do not prevent falls or fall-related injuries? PMID- 27396289 TI - Modeling Longitudinal Metabonomics and Microbiota Interactions in C57BL/6 Mice Fed a High Fat Diet. AB - Longitudinal studies aim typically at following populations of subjects over time and are important to understand the global evolution of biological processes. When it comes to longitudinal omics data, it will often depend on the overall objective of the study, and constraints imposed by the data, to define the appropriate modeling tools. Here, we report the use of multilevel simultaneous component analysis (MSCA), orthogonal projection on latent structures (OPLS), and regularized canonical correlation analysis (rCCA) to study associations between specific longitudinal urine metabonomics data and microbiome data in a diet induced obesity model using C57BL/6 mice. (1)H NMR urine metabolic profiling was performed on samples collected weekly over a period of 13 weeks, and stool microbial composition was assessed using 16S rRNA gene sequencing at three specific time periods (baseline, first week response, end of study). MSCA and OPLS allowed us to explore longitudinal urine metabonomics data in relation to the dietary groups, as well as dietary effects on body weight. In addition, we report a data integration strategy based on regularized CCA and correlation analyses of urine metabonomics data and 16S rRNA gene sequencing data to investigate the functional relationships between metabolites and gut microbial composition. Thanks to this workflow enabling the breakdown of this data set complexity, the most relevant patterns could be extracted to further explore physiological processes at an anthropometric, cellular, and molecular level. PMID- 27396291 TI - Effects of in vitro fermentation of barley beta-glucan and sugar beet pectin using human fecal inocula on cytokine expression by dendritic cells. AB - SCOPE: This study simulates the fermentation process of barley beta-glucan and sugar beet pectin in the human colon and monitors the degradation products formed. Additionally, immune effects of the degradation products were investigated. METHODS AND RESULTS: Immunostimulatory activity of fermentation digesta was investigated using bone marrow derived dendritic cells (BMDCs) from toll-like receptor 2/4 (TLR2/4) knockout mice, which were unresponsive to microbe associated molecular patterns. Cytokine responses were elicited to dietary fibers and not to the SCFA and microbiota. The fermentation digesta were analyzed for their SCFA profiles and glycan metabolites over time. During fermentation the amount of insoluble precipitating fibers increased and induced as well as soluble molecules of lower molecular mass greater amounts of cytokines in BMDCs than the parental fiber. Additionally, high amounts of cytokines can be attributed to soluble galactose-rich beet pectin molecules. CONCLUSIONS: The fermentation of the two fibers led to fiber-specific amounts of SCFA, glycosidic metabolites, and different immunomodulatory properties. BMDC from TLR2/4 knockout mice did not respond to the digest microbiota and SCFA, making it a useful approach to study temporal effects of fermentation on the immunomodulatory effects of fibers. PMID- 27396292 TI - Developing a data repository of standard concussion assessment clinical data for research involving college athletes. AB - In sports concussion research, obtaining quality data from a sufficient number of participants to reach statistical power has been a particular problem. In addition, the necessary requirements of accessibility, informed consent, and confidentiality must be met. There is need to develop more efficient and controlled methods for collecting data to answer research questions in this realm, but the ability to collect and store these data in an efficient manner at the local level is limited. By virtue of their training, neuropsychologists can play a key role in improving data collection quality. The purpose of this paper is to describe a data repository that has been developed in the context of a university sports medicine concussion management program that includes baseline and postinjury data from student athletes. Diagnostic information, basic health information, current symptoms, neuropsychological test data, balance and vestibular data, and visual processing data are currently included in the standard of care for athletes; however, the process described need not be limited to these types of data. While a national traumatic brain injury (TBI) data repository has been developed by the National Institute of Health (NIH), local repositories have not yet become common. Thus, the description of this project is of value at the local level in the United States and internationally. PMID- 27396293 TI - Intensified nitrogen removal in immobilized nitrifier enhanced constructed wetlands with external carbon addition. AB - Nitrogen removal performance response of twelve constructed wetlands (CWs) to immobilized nitrifier pellets and different influent COD/N ratios (chemical oxygen demand: total nitrogen in influent) were investigated via 7-month experiments. Nitrifier was immobilized on a carrier pellet containing 10% polyvinyl alcohol (PVA), 2.0% sodium alginate (SA) and 2.0% calcium chloride (CaCl2). A batch experiment demonstrated that 73% COD and 85% ammonia nitrogen (NH4-N) were degraded using the pellets with immobilized nitrifier cells. In addition, different carbon source supplement strategies were applied to remove the nitrate (NO3-N) transformed from NH4-N. An increase in COD/N ratio led to increasing reduction in NO3-N. Efficient nitrification and denitrification promoted total nitrogen (TN) removal in immobilized nitrifier biofortified constructed wetlands (INB-CWs). The results suggested that immobilized nitrifier pellets combined with high influent COD/N ratios could effectively improve the nitrogen removal performance in CWs. PMID- 27396294 TI - Multiple scattering dynamics of fermions at an isolated p-wave resonance. AB - The wavefunction for indistinguishable fermions is anti-symmetric under particle exchange, which directly leads to the Pauli exclusion principle, and hence underlies the structure of atoms and the properties of almost all materials. In the dynamics of collisions between two indistinguishable fermions, this requirement strictly prohibits scattering into 90 degrees angles. Here we experimentally investigate the collisions of ultracold clouds fermionic (40)K atoms by directly measuring scattering distributions. With increasing collision energy we identify the Wigner threshold for p-wave scattering with its tell-tale dumb-bell shape and no 90 degrees yield. Above this threshold, effects of multiple scattering become manifest as deviations from the underlying binary p wave shape, adding particles either isotropically or axially. A shape resonance for (40)K facilitates the separate observation of these two processes. The isotropically enhanced multiple scattering mode is a generic p-wave threshold phenomenon, whereas the axially enhanced mode should occur in any colliding particle system with an elastic scattering resonance. PMID- 27396295 TI - Herbal remedies for perceived inadequate milk supply are perhaps not as safe as women think: A brief case report. PMID- 27396297 TI - Patient Perspectives: What is a port-wine stain (also known as a port-wine birthmark)? PMID- 27396296 TI - Culturally capable and culturally safe: Caseload care for Indigenous women by Indigenous midwifery students. AB - BACKGROUND: Evidence is emerging of the benefits to students of providing continuity of midwifery care as a learning strategy in midwifery education, however little is known about the value of this strategy for midwifery students. AIM: To explore Indigenous students' perceptions of providing continuity of midwifery care to Indigenous women whilst undertaking a Bachelor of Midwifery. METHODS: Indigenous Bachelor of Midwifery students' experiences of providing continuity of midwifery care to Indigenous childbearing women were explored within an Indigenous research approach using a narrative inquiry framework. Participants were three Indigenous midwifery students who provided continuity of care to Indigenous women. FINDINGS: Three interconnected themes; facilitating connection, being connected, and journeying with the woman. These themes contribute to the overarching finding that the experience of providing continuity of care for Indigenous women creates a sense of personal affirmation, purpose and a validation of cultural identity in Indigenous students. DISCUSSION AND CONCLUSIONS: Midwifery philosophy aligns strongly with the Indigenous health philosophy and this provides a learning platform for Indigenous student midwives. Privileging Indigenous culture within midwifery education programs assists students develop a sense of purpose and affirms them in their emerging professional role and within their community. The findings from this study illustrate the demand for, and pertinence of, continuity of care midwifery experiences with Indigenous women as fundamental to increasing the Indigenous midwifery workforce in Australia. Australian universities should provide this experience for Indigenous student midwives. PMID- 27396298 TI - Congenital Papule on the Anterior Neck. PMID- 27396299 TI - A Three-Year-Old Girl Who Never Needs a Haircut. PMID- 27396300 TI - Recurrence of Two Nodules on the Toe of a 10-Year-Old Boy. PMID- 27396301 TI - Generalized Hyperkeratotic Plaques in a Baby with a Milk Allergy. PMID- 27396302 TI - Chikungunya: What We Need to Know. PMID- 27396305 TI - Recent improvements in the management of esophageal anastomotic leak after surgery for cancer. AB - Anastomotic leakage following total gastrectomy or esophagectomy is a significant complication that considerably increases postoperative mortality. The location of the anastomosis together with the anatomy of the esophagus explains the severity of this complication. Surgical knowledge should include general and specific predictive factors of leakage to avoid any technical-related cause of leakage. Clinical presentations may vary from minimally symptomatic to life-threatening situations. Investigations should be undertaken as soon as the diagnosis is suspected because delay greatly worsens the prognosis. CT scans with oral contrast and low insufflation early endoscopy are the preferred diagnostic tools and can also aid in therapeutic procedures. Communication and multidisciplinary teamwork are the cornerstones of treatment. When the leak occurs early with acute and important sepsis, the recommendation is surgical treatment. On the contrary, if the leak is late, non-symptomatic or minimally symptomatic, conservative management with intensive surveillance could be proposed. When the situation is in between these two extremes, endoscopic treatment is often proposed. Based on a review of the literature and experience from high volume centers, in this educational review, we present the incidence, predictive factors, clinical presentations, diagnostic tools, management, and therapeutic algorithms for anastomotic leaks following elective esophagectomy and total gastrectomy for cancer. PMID- 27396306 TI - Regulation of retinol-binding protein 4 and retinol metabolism in fatty liver disease. PMID- 27396304 TI - MicroRNAs in Neurocognitive Dysfunctions: New Molecular Targets for Pharmacological Treatments? AB - BACKGROUND: Neurodegenerative and cognitive disorders are multifactorial diseases (i.e., involving neurodevelopmental, genetic, age or environmental factors) characterized by an abnormal development that affects neuronal function and integrity. Recently, an increasing number of studies revealed that the dysregulation of microRNAs (miRNAs) may be involved in the etiology of cognitive disorders as Alzheimer, Parkinson, and Huntington's diseases, Schizophrenia and Autism spectrum disorders. METHODS: From an extensive search in bibliographic databases of peer-reviewed research literature, we identified relevant published studies related to specific key words such as memory, cognition, neurodegenerative disorders, neurogenesis and miRNA. We then analysed, evaluated and summerized scientific evidences derived from these studies. RESULTS: We first briefly summarize the basic molecular events involved in memory, a process inherent to cognitive disease, and then describe the role of miRNAs in neurodevelopment, synaptic plasticity and memory. Secondly, we provide an overview of the impact of miRNA dysregulation in the pathogenesis of different neurocognitive disorders, and lastly discuss the feasibility of miRNA-based therapeutics in the treatment of these disorders. CONCLUSION: This review highlights the molecular basis of neurodegenerative and cognitive disorders by focusing on the impact of miRNAs dysregulation in these pathological phenotypes. Altogether, the published reports suggest that miRNAs-based therapy could be a viable therapeutic alternative to current treatment options in the future. PMID- 27396307 TI - Developing a framework for assessing chemical respiratory sensitization: A workshop report. AB - Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, -omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non-immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment. PMID- 27396308 TI - Microinjection-based generation of mutant mice with a double mutation and a 0.5 Mb deletion in their genome by the CRISPR/Cas9 system. AB - The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein 9 (Cas9) system is a useful tool for genome editing. In this study, using a microinjection-based CRISPR/Cas9 system, we efficiently generated mouse lines carrying mutations at the Irx3 and Irx5 loci, which are located in close proximity on a chromosome and are functionally redundant. During the generation of Irx3/Irx5 double mutant mice, a deletion of ~0.5 Mb between the Irx3 and Irx5 loci was unintentionally identified in 6 out of 27 living pups by PCR based genotyping analysis. This deletion was confirmed by DNA fluorescence in situ hybridization analysis of fibroblasts. These results indicate that the mutant mice with a deletion of at least 0.5 Mb in their genome can be generated by the CRISPR/Cas9 system through microinjection into fertilized eggs. Our findings expand the utility of the CRISPR/Cas9 system in production of disease model animals with large deletions. PMID- 27396309 TI - Synthesis of novel 5-arylidenethiazolidinones with apoptotic properties via a three component reaction using piperidine as a bifunctional reagent. AB - The synthesis of a new library of 5-arylidenethiazolidinone compounds using an efficient three component reaction with thiazolidine-2,4-dione, piperidine and appropriate aldehydes is reported. This reaction is excellently high yielding, tolerant towards a variety of aldehydes and provides access to these compounds in a single step (in comparison to low yielding multistep syntheses reported in the literature). Once the reaction is complete, the desired product precipitates out of the reaction mixture and is isolated by filtration and purified by washing and recrystallization. These compounds revealed anti-proliferative activities against human breast cancer cells (MCF7 and MDA). Phenotypic profiling established the most active compound 17i (EC50 = 4.52 MUM) as an apoptotic agent. A novel chemical proteomics approach identified beta-actin-like protein 2, gamma-enolase and macrophage migration inhibitory factor (MMIF) as putative cellular binding partners of 17i. PMID- 27396310 TI - The artificial ovary: current status and future perspectives. AB - Cryopreservation and transplantation of ovarian tissue has proved to be a promising technique to safeguard fertility in cancer patients. However, with some types of cancer, there is a risk of transmitting malignant cells present in the cryopreserved tissue, so transplantation after disease remission is not advisable. To restore fertility in these patients, some research teams have been developing a transplantable artificial ovary, whose main goal is to mimic the natural organ. It should be composed of a matrix that encapsulates and protects follicles, as well as ovarian cells, which are necessary for follicle survival and development. This article reviews progress made in the creation of a transplantable artificial ovary and discusses future trends for its development. PMID- 27396311 TI - Hybrid Moving Bed Biofilm Reactor for the biodegradation of benzotriazoles and hydroxy-benzothiazole in wastewater. AB - A laboratory scale Hybrid Moving Bed Biofilm Reactor (HMBBR) was used to study the removal of five benzotriazoles and one benzothiazole from municipal wastewater. The HMBBR system consisted of two serially connected fully aerated bioreactors that contained activated sludge (AS) and K3-biocarriers and a settling tank. The average removal of target compounds ranged between 41% (4 methyl-1H-benzotriazole; 4TTR) and 88% (2-hydroxybenzothiazole; OHBTH). Except for 4TTR, degradation mainly occurred in the first bioreactor. Calculation of biodegradation constants in batch experiments and application of a model for describing micropollutants removal in the examined system showed that AS is mainly involved in biodegradation of OHBTH, 1H-benzotriazole (BTR) and xylytriazole (XTR), carriers contribute significantly on 4TTR biodegradation, while both types of biomass participate on elimination of 5-chlorobenzotriazole (CBTR) and 5-methyl-1H-benzotriazole (5TTR). Comparison of the HMBBR system with MBBR or AS systems from literature showed that the HMBBR system was more efficient for the biodegradation of the investigated chemicals. Biotransformation products of target compounds were identified using ultra high-performance liquid chromatography, coupled with a quadrupole-time-of-flight high-resolution mass spectrometer (UHPLC-QToF-MS). Twenty two biotransformation products were tentatively identified, while retention time denoted the formation of more polar transformation products than the parent compounds. PMID- 27396312 TI - Water quality monitoring strategies - A review and future perspectives. AB - The reliable assessment of water quality through water quality monitoring programs (WQMPs) is crucial in order for decision-makers to understand, interpret and use this information in support of their management activities aiming at protecting the resource. The challenge of water quality monitoring has been widely addressed in the literature since the 1940s. However, there is still no generally accepted, holistic and practical strategy to support all phases of WQMPs. The purpose of this paper is to report on the use cases a watershed manager has to address to plan or optimize a WQMP from the challenge of identifying monitoring objectives; selecting sampling sites and water quality parameters; identifying sampling frequencies; considering logistics and resources to the implementation of actions based on information acquired through the WQMP. An inventory and critique of the information, approaches and tools placed at the disposal of watershed managers was proposed to evaluate how the existing information could be integrated in a holistic, user-friendly and evolvable solution. Given the differences in regulatory requirements, water quality standards, geographical and geological differences, land-use variations, and other site specificities, a one-in-all solution is not possible. However, we advance that an intelligent decision support system (IDSS) based on expert knowledge that integrates existing approaches and past research can guide a watershed manager through the process according to his/her site-specific requirements. It is also necessary to tap into local knowledge and to identify the knowledge needs of all the stakeholders through participative approaches based on geographical information systems and adaptive survey-based questionnaires. We believe that future research should focus on developing such participative approaches and further investigate the benefits of IDSS's that can be updated quickly and make it possible for a watershed manager to obtain a timely, holistic view and support for every aspect of planning and optimizing a WQMP. PMID- 27396313 TI - Meteorological and hydrological conditions driving the formation and disappearance of black blooms, an ecological disaster phenomena of eutrophication and algal blooms. AB - Potentially toxic black blooms can disrupt drinking water treatment plants and have fatal effects on aquatic ecosystems; therefore, lake management is required to determine whether conditions are favorable for the formation and disappearance of black blooms in water supply sources. Long-term climate background, short-term thresholds of meteorological and hydrological conditions, and the duration of harmful algal blooms (HABs) were investigated as factors affecting the formation and disappearance of black blooms in hyper-eutrophic Lake Taihu. Long-term climate warming (0.31 degrees C/decade), decreases in wind speed (0.26m/s per decade) and air pressure (0.16hPa/decade), and the increase in the meteorological index of black blooms (3.6days/decade) in Lake Taihu over the past 51years provided climate conditions conducive to the formation and occurrence of black blooms. A total of 16 black bloom events with an area larger than 0.1km(2) were observed from 2007 to 2014. Several critical thresholds for short-term meteorological and hydrological conditions were determined for the formation of black blooms, including a five-day average air temperature above 25 degrees C, a five-day average wind speed <2.6m/s, average precipitation of five consecutive days close to 0, and continuous HAB accumulation for >5days. Heavy precipitation events, sudden cooling, and large wind disturbances were the driving factors of black blooms' disappearance. The use of a coupling model that combines the remote sensing of HABs with environmental, meteorological, and hydrological observations could permit an adequate and timely response to black blooms in drinking water sources. PMID- 27396314 TI - Multigenerational effect of perfluorooctane sulfonate (PFOS) on the individual fitness and population growth of Daphnia magna. AB - We investigated the multigenerational effect of PFOS to individual fitness (e.g., body weight, acetylcholinesterase and glutathione S-transferase) and population growth (e.g., offspring number and time to first brood) of Daphnia magna during continuous and discontinuous exposures. The intrinsic rate of population growth was also calculated. In the continuous exposure, population growth-related adverse effects were detected during all test periods, and the adverse effect tended to be weaker in later generations. On the other hand, individual fitness related adverse effects were observed from F1 not in F0 and deteriorated as the generation number increased. These results imply that individual fitness worsens although the population growth is restored in later generations. Upon discontinuous exposure, a few but significant adverse effects were observed during the non-exposure period and highest effects were detected during the re exposure period. This encourages the study of different exposure scenarios, which may result in unexpected and higher PFOS toxicity. Consequently, this study confirms adverse effects of PFOS to Daphnia magna in multigenerational period and supports reasons for studies linking individual fitness changes to population dynamics and covering diverse exposure scenarios to evaluate the risk of PFOS in a water environment. PMID- 27396315 TI - Temporal stability of chemical hormesis (CH): Is CH just a temporary stop on the road to thresholds and toxic responses? AB - Chemical hormesis (CH) is currently described as a nonmonotonic, bidirectional dose-response relationship for chemicals, where a stimulatory, (beneficial?) response at low dose or exposure is followed by an inhibitory response at higher doses/exposures (or vice-versa). CH is depicted as U(J)-shaped or inverse U(J) shaped curves, i.e., curve slopes change sign. Some describe CH as a homeostasis preserving response; others view CH as adaptive or (pre)conditioning responses to chemical stress. One aspect of CH and stress hormesis in general that has not been researched is its temporal stability, i.e., persistence, particularly in experimental animals and humans having long-term chemical stressing. Once maximized, does the CH response remain operative over the entire time of chemical exposure? One possible reason for the question's neglect is that temporal stability, e.g., 'steady-state hormesis,' has been assumed. Another is that CH temporality is not well understood or has been under-appreciated as to its importance. Available data, mainly for simpler biological systems, describe cases of transitory CH. Other examples, in human and experimental animal studies, show transitory existence of CH and, in some specialized cases, persisting CH. Also, certain disease state-induced hormetic responses are transitory over time in humans. The question requires resolution if CH is to be considered (i) a stable and beneficial or adverse response, (ii) a stable dose-response model competitive with stable threshold and linear, nonthreshold (LNT) dose-response models, and (iii) a model having any impact on, or role in, regulatory and public health policies. PMID- 27396316 TI - Relationships between urinary antimony levels and both mortalities and prevalence of cancers and heart diseases in general US population, NHANES 1999-2010. AB - The effects of antimony (Sb) exposure on mortalities, cancers and cardiovascular diseases were controversial in occupational workers, and the evidence from the general population is limited. The objective of this study is to investigate the relationships between Sb exposure and specific health events in the general population. Totally, 7781 participants aged >=20years were selected from the National Health and Nutrition Examination Survey (NHANES) 1999-2010 and were followed for an average of 6.04years. The Cox and logistic regression models were applied to evaluate the effects of urinary Sb (U-Sb) levels on the risks of all cause and cause-specific mortalities, and the likelihoods of self-reported cancers and heart diseases, respectively. When setting quartile 1 of U-Sb levels as reference, the hazard ratios (HRs) [95% confidence intervals (CIs)] of the quartile 2 through 4 for all-cause mortality were 1.21 (0.84, 1.74), 1.49 (1.08, 2.04) and 1.66 (1.20, 2.28). The HR of quartile 3 of U-Sb levels for heart disease mortality was 2.18 (1.24, 3.86). Furthermore, increased odds ratios (ORs) from quartile 2 to 4 were 1.69 (1.05, 2.74), 1.42 (0.79, 2.55) and 2.11 (1.26, 3.55) for self-reported congestive heart failure, and 1.37 (0.95, 1.99), 1.96 (1.37, 2.82) and 1.81 (1.16, 2.83) for heart attack. Elevated U-Sb levels were not significantly related to mortality of malignant neoplasms, and self-reported cancers. The data demonstrated associations of increased U-Sb levels with all cause and heart diseases mortalities, and prevalent congestive heart failure and heart attack, suggesting public concerns on the health hazards of Sb exposure in the general population. PMID- 27396317 TI - Concentrations and potential health hazards of polycyclic aromatic hydrocarbon in shallow groundwater of a metal smelting area in Southeastern China. AB - A total of 20 shallow groundwater samples were collected from a metal smelting area in southeastern China to determine the concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs), calculate their toxic equivalents (TEQs) to benzo[a]pyrene (BaP), and estimate the carcinogenic risk of drinking the shallow groundwater. The total concentrations of the 16PAHs (?PAHs) in the shallow groundwater ranged from 9.62 to 1663.93ngL(-1), with a mean value of 312.63ngL(-1), and the total concentrations of the 7 potentially carcinogenic PAHs (?PAHC7) ranged from 3.11 to 33.60ngL(-1), with a mean value of 9.61ngL(-1). Naphthalene and BaP, were the dominant PAH species and potentially carcinogenic PAH species in the shallow groundwater of the study area, and they account for 89.97% of ?PAHs and 82.62% of ?PAHC7, respectively. High molecular weight-PAHs (HM-PAHs) accounted for a relatively high proportion in the majority of shallow groundwater samples with lower concentrations of SigmaPAHs, indicated that HM PAHs were mainly from historical residues. The TEQs to BaP of the 16PAHs in the 20 shallow groundwater samples varied greatly from 2.55 to 32.73ngL(-1), with a mean value of 8.61ngL(-1), and BaP was the dominant contributor. The total carcinogenic risk levels caused by the 16PAHs in the shallow groundwater in majority of the area were found to be higher than the limit set by the US EPA, posing a potentially serious health risk to those who depend on shallow groundwater for drinking water. PMID- 27396318 TI - Developing and sustainably utilize the coastal mudflat areas in China. AB - Coastal mudflat areas are regarded as the important reserve land resource in China. Rational exploitation and development of the mudflat areas can relieve the stress of inadequate land resources. Probing into the developing models of resource exploitation of coastal tidal mudflats is one of the important components of achieving the sustainable development in the coastal areas. Therefore, the development history of coastal mudflats after 1950s in China is briefly introduced in this paper. Then, the status in quo of the modes of development and utilization of coastal mudflat in China the paper is reviewed with a special attention payed to the agricultural use of coastal resource, especially halophytes and improved salt-tolerant varieties planting, agricultural dyke pond and coastal saline-alkali soil remediation. Based on related research frontier, sustainable developmental prospects of these coastal areas are presented as well. PMID- 27396319 TI - The responses of soil respiration to nitrogen addition in a temperate grassland in northern China. AB - Anthropogenic activities have increased nitrogen (N) inputs to grassland ecosystems. Knowledge of the impact of soil N availability on soil respiration (RS) is critical to understand soil carbon balances and their responses to global climate change. A 2-year field experiment was conducted to evaluate the response of RS to soil mineral N in a temperate grassland in northern China. RS, abiotic and biotic factors, and N mineralization were measured in the grassland, at rates of N addition ranging from 0 to 25gNm(-2)yr(-1). Annual and dormant-season RS ranged from 241.34 to 283.64g C m(-2) and from 61.34 to 83.84g C m(-2) respectively. High N application significantly increased RS, possibly due to increased root biomass and increased microbial biomass. High N treatment significantly increased soil NO3-N and inorganic N content compared with the control. The ratio of NO3-N to NH4-N and the N mineralization rate were significantly positively correlated with RS, but NH4-N was not correlated or negatively correlated with RS during the growing season. The temperature sensitivity of RS (Q10) was not significantly affected by N levels, and ranged from 1.90 to 2.20, but decreased marginally significantly at high N. RS outside the growing season is an important component of annual RS, accounting for 25.0 to 29.6% of the total. High N application indirectly stimulated RS by increasing soil NO3-N and net nitrification, thereby eliminating soil N limitations, promoting ecosystem productivity, and increasing soil CO2 efflux. Our results show the importance of distinguishing between NO3-N and NH4-N, as their impact on soil CO2 efflux differed. PMID- 27396320 TI - Dynamic sediment discharge in the Hekou-Longmen region of Yellow River and soil and water conservation implications. AB - The middle reaches of the Yellow River Basin transport the vast majority of sediment (>85% of the basin's total available sediment load), which has had profound effects on the characteristics of the middle and lower reaches of the Yellow River. Since the late 1950s, soil and water conservation measures have been extensively implemented in the Loess Plateau, China, especially since the 1970s. This has resulted in sediment discharge changing significantly. In this study, data from 22 catchments in the region of the Loess Plateau from Hekou to Longmen in the middle reaches of the Yellow River were analyzed to investigate the responses of the sediment regime to climate change and human activities. The non-parametric Mann-Kendall test and the Pettitt test were used to identify trends and shifts in sediment discharge. All 22 catchments had a significantly decreasing trend (P<0.01) in annual sediment discharge. Change point years were detected between 1971 and 1994, and were concentrated between 1978 and 1984 in 17 catchments. Moreover, erosive rainfall exhibited a tendency to decrease, but this was not a significant trend. Compared to rainfall, human activities, primarily soil and water conservation and environmental rehabilitation campaigns, have played a more prominent role in the changes in sediment regimes. In order to reduce soil erosion and sediment yield, more attention should be paid to proper and rational soil and water conservation and eco-restoration in this region. PMID- 27396321 TI - The effects of peeling and cooking on the mineral content and antioxidant properties in carrots enriched with potassium iodate and/or selenite (Se(IV)) and selenite (Se(VI)). AB - Research covered six variants: control, unfertilized carrots and carrots fertilized with: KIO3, Na2SeO4, Na2SeO3, KIO3 and simultaneously with Na2SeO4, and fertilized with KIO3 and simultaneously Na2SeO3. Carrots enriched with iodate or selenite, or both iodate and selenite, were characterized by higher amount of these minerals. Changes to the content of micro- and macroelements, during the cooking time of the carrots, both in peeled and unpeeled carrots, did not head in the same direction (increase, decrease and no change). However, cooking an unpeeled carrot generally resulted in the increased content of polyphenol and carotenoids. On the other hand, cooking peeled carrots led to a decrease in the content of polyphenol and a general lack of change in carotenoid content in relation to the unpeeled cooked carrot. During cooking, the antioxidant activity of the carrot being assessed changed together with the direction of changes in polyphenol content but not in line with the direction of changes in carotenoids. PMID- 27396322 TI - Tooth loss and alveolar bone crest loss during supportive periodontal therapy in patients with generalized aggressive periodontitis: retrospective study with follow-up of 8 to 15 years. AB - AIM: To determine the incidence of tooth loss in patients with generalized aggressive periodontitis (GAgP) during supportive periodontal therapy (SPT), identify tooth loss risk factors, and quantify alveolar crest height changes on periapical X-ray during follow-up. MATERIAL AND METHODS: This retrospective study included 25 GAgP patients with 656 teeth after periodontal treatment (baseline). Data were gathered on sociodemographic, periodontal, and radiological variables at baseline and at the end of follow-up. Linear regression models were used to assess the association of risk factors with tooth loss. RESULTS: Twenty-eight teeth were extracted during SPT. The mean tooth loss per patient was 1.12 +/- 2.01 for all causes and 0.9 +/- 2.0 for periodontal disease after a mean follow up of 10.9 +/- 2 years. Clinical variables were improved at the end of follow-up, with a mean reduction of -1 +/- 0.8 mm in probing pocket depth (-0.7 to -1.3, 95% CI) and -0.6 +/- 0.9 mm in clinical attachment loss (-0.9 to -0.2, 95% CI). Mean alveolar bone crest loss at the end of follow-up was 0.36 +/- 0.56 mm (0.10-0.61, 95% CI). Smoking was associated with tooth loss (p = 0.052). CONCLUSIONS: Tooth loss rate was low in GAgP in a regular supportive care programme. Clinical variables improved, and bone loss was minimal over time. Smoking was associated with tooth loss. PMID- 27396323 TI - Reflections on the Insertion and Fracture Forces of Microneedles. AB - BACKGROUND: The use of microneedles for transdermal drug delivery is a feasible alternative to injections and tablets. As different types of microneedles are being developed from a variety of materials, it is important to understand their insertion and fracture forces. In this review, it has been emphasized that for microneedles to be clinically useful, they must penetrate the skin without breaking. It means that the insertion force must be smaller than fracture force. METHODS: Transdermal experiments involving these forces have been described and theoretical models highlighted. The knowledge of these forces is important for microneedle design and experimental/ clinical use. RESULTS: From an experimental standpoint, different techniques are used to measure insertion and fracture forces. To measure insertion and failure forces, a texture analyzer can be used. In this review, the measurement of insertion and fracture forces has been discussed and their utility in transdermal experiments presented. CONCLUSION: This review has focused on insertion and failure forces in transdermal drug delivery experiments. Although the question is complex since there is a wide variety of skin models and forces involved, studies carried out in the last few years have thrown more light to aid better understanding of these forces in transdermal drug delivery research. PMID- 27396324 TI - Optogenetic Control of Nodal Signaling Reveals a Temporal Pattern of Nodal Signaling Regulating Cell Fate Specification during Gastrulation. AB - During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation. PMID- 27396325 TI - Regulation of Nuclear Hormone Receptors by MYCN-Driven miRNAs Impacts Neural Differentiation and Survival in Neuroblastoma Patients. AB - MYCN amplification and MYC signaling are associated with high-risk neuroblastoma with poor prognosis. Treating these tumors remains challenging, although therapeutic approaches stimulating differentiation have generated considerable interest. We have previously shown that the MYCN-regulated miR-17~92 cluster inhibits neuroblastoma differentiation by repressing estrogen receptor alpha. Here, we demonstrate that this microRNA (miRNA) cluster selectively targets several members of the nuclear hormone receptor (NHR) superfamily, and we present a unique NHR signature associated with the survival of neuroblastoma patients. We found that suppressing glucocorticoid receptor (GR) expression in MYCN-driven patient and mouse tumors was associated with an undifferentiated phenotype and decreased survival. Importantly, MYCN inhibition and subsequent reactivation of GR signaling promotes neural differentiation and reduces tumor burden. Our findings reveal a key role for the miR-17~92-regulated NHRs in neuroblastoma biology, thereby providing a potential differentiation approach for treating neuroblastoma patients. PMID- 27396326 TI - The Hidden Complexity of Mendelian Traits across Natural Yeast Populations. AB - Mendelian traits are considered to be at the lower end of the complexity spectrum of heritable phenotypes. However, more than a century after the rediscovery of Mendel's law, the global landscape of monogenic variants, as well as their effects and inheritance patterns within natural populations, is still not well understood. Using the yeast Saccharomyces cerevisiae, we performed a species-wide survey of Mendelian traits across a large population of isolates. We generated offspring from 41 unique parental pairs and analyzed 1,105 cross/trait combinations. We found that 8.9% of the cases were Mendelian. Further tracing of causal variants revealed background-specific expressivity and modified inheritances, gradually transitioning from Mendelian to complex traits in 30% of the cases. In fact, when taking into account the natural population diversity, the hidden complexity of traits could be substantial, confounding phenotypic predictability even for simple Mendelian traits. PMID- 27396327 TI - miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle. AB - Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC). Short-term high-fat diet (HFD) feeding reduces muscle miR-182 levels by tumor necrosis factor alpha (TNFalpha), which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control. PMID- 27396329 TI - Cdc42-Dependent Forgetting Regulates Repetition Effect in Prolonging Memory Retention. AB - Repeated learning is used daily and is a powerful way to improve memory. A fundamental question is how multiple learning trials add up to improve memory. While the major studies so far of such a repetition effect have emphasized the strengthening of memory formation, the current study reveals a molecular mechanism through suppression of forgetting. We find that single-session training leads to formation of anesthesia-resistant memory (ARM) and then activation of the small G protein Cdc42 to cause decay or forgetting of ARM within 24 hr. Repetition suppresses the activation of Cdc42-dependent forgetting, instead of enhancing ARM formation, leading to prolonged ARM. Consistently, inhibition of Cdc42 activity through genetic manipulation mimicked the repetition effect, while repetition-induced ARM improvement was abolished by elevated Cdc42 activity. Thus, only the first session in repetitive training contributes to ARM formation, while the subsequent sessions are devoted not to acquiring information but to inhibiting forgetting. PMID- 27396328 TI - SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation. AB - Osteoblasts and adipocytes are derived from a common precursor, mesenchymal stem cells (MSCs). Alterations in the normal fate of differentiating MSCs are involved in the development of obesity and osteoporosis. Here, we report that viable motheaten (me(v)) mice, which are deficient in the SH2-domain-containing phosphatase-1 (SHP1), develop osteoporosis spontaneously. Consistently, MSCs from me(v)/me(v) mice exhibit significantly reduced osteogenic potential and greatly increased adipogenic potential. When MSCs were transplanted into nude mice, SHP1 deficient MSCs resulted in diminished bone formation compared with wild-type MSCs. SHP1 was found to bind to GSK3beta and suppress its kinase activity by dephosphorylating pY216, thus resulting in beta-catenin stabilization. Mice, in which SHP1 was deleted in MSCs using SHP1(fl/fl)Dermo1-cre, displayed significantly decreased bone mass and increased adipose tissue. Taken together, these results suggest a possible role for SHP1 in controlling tissue homeostasis through modulation of MSC differentiation via Wnt signaling regulation. PMID- 27396330 TI - Lack of Transcription Triggers H3K27me3 Accumulation in the Gene Body. AB - Trimethylated H3K27 (H3K27me3) is associated with transcriptional repression, and its abundance in chromatin is frequently altered in cancer. However, it has remained unclear how genomic regions modified by H3K27me3 are specified and formed. We previously showed that downregulation of transcription by oncogenic Ras signaling precedes upregulation of H3K27me3 level. Here, we show that lack of transcription as a result of deletion of the transcription start site of a gene is sufficient to increase H3K27me3 content in the gene body. We further found that histone deacetylation mediates Ras-induced gene silencing and subsequent H3K27me3 accumulation. The H3K27me3 level increased gradually after Ras activation, requiring at least 35 days to achieve saturation. Such maximal accumulation of H3K27me3 was reversed by forced induction of transcription with the dCas9-activator system. Thus, our results indicate that changes in H3K27me3 level, especially in the body of a subset of genes, are triggered by changes in transcriptional activity itself. PMID- 27396331 TI - GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway. AB - A surface marker that distinctly identifies cardiac progenitors (CPs) is essential for the robust isolation of these cells, circumventing the necessity of genetic modification. Here, we demonstrate that a Glycosylphosphatidylinositol anchor containing neurotrophic factor receptor, Glial cell line-derived neurotrophic factor receptor alpha 2 (Gfra2), specifically marks CPs. GFRA2 expression facilitates the isolation of CPs by fluorescence activated cell sorting from differentiating mouse and human pluripotent stem cells. Gfra2 mutants reveal an important role for GFRA2 in cardiomyocyte differentiation and development both in vitro and in vivo. Mechanistically, the cardiac GFRA2 signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase and its established ligands. Collectively, our findings establish a platform for investigating the biology of CPs as a foundation for future development of CP transplantation for treating heart failure. PMID- 27396332 TI - Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics. AB - Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network. PMID- 27396333 TI - Regulation of Hepatic Triacylglycerol Metabolism by CGI-58 Does Not Require ATGL Co-activation. AB - Adipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI 58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of CGI-58 occurs in vivo. Moreover, the phenotype of human CGI-58 mutations suggests ATGL-independent functions. Through direct comparison of mice with single or double deficiency of CGI-58 and ATGL, we show here that CGI-58 knockdown causes hepatic steatosis in both the presence and absence of ATGL. CGI-58 also regulates hepatic diacylglycerol (DAG) and inflammation in an ATGL-independent manner. Interestingly, ATGL deficiency, but not CGI-58 deficiency, results in suppression of the hepatic and adipose de novo lipogenic program. Collectively, these findings show that CGI-58 regulates hepatic neutral lipid storage and inflammation in the genetic absence of ATGL, demonstrating that mechanisms driving TAG lipolysis in hepatocytes differ significantly from those in adipocytes. PMID- 27396334 TI - Somatostatin Interneurons Control a Key Component of Mismatch Negativity in Mouse Visual Cortex. AB - Patients with schizophrenia have deficient sensory processing, undermining how they perceive and relate to a changing environment. This impairment can be captured by the reduced mismatch negativity (MMN) index, an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, in which genetic and optical methods could be applied, has given some insight. Using fast two-photon calcium imaging and multielectrode recordings in awake mice, we find that visual cortical circuits display adapted (decreased) responses to repeated stimuli and amplified responses to a deviant stimulus, the key component of human MMN. Moreover, pharmacogenetic silencing of somatostatin-containing interneurons specifically eliminated this amplification, along with its associated theta/alpha band response, leaving stimulus-specific adaption and related gamma-band modulations intact. Our results validate a mouse model of MMN and suggest that abnormalities in somatostatin-containing interneurons cause sensory deficits underlying MMN and schizophrenia. PMID- 27396335 TI - MouSensor: A Versatile Genetic Platform to Create Super Sniffer Mice for Studying Human Odor Coding. AB - Typically, ~0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these "MouSensors." In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 MouSensor. Moreover, a behavioral avoidance task demonstrates that specific odor detection thresholds are significantly decreased in multiple transgenic lines, expressing mouse or human ORs. We have developed a versatile platform to study gene choice and axon identity, to create biosensors with great translational potential, and to finally decode human olfaction. PMID- 27396336 TI - Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2. AB - FGF21 contributes to the metabolic response to dietary protein restriction, and prior data implicate GCN2 as the amino acid sensor linking protein restriction to FGF21 induction. Here, we demonstrate the persistent and essential role of FGF21 in the metabolic response to protein restriction. We show that Fgf21 KO mice are fully resistant to low protein (LP)-induced changes in food intake, energy expenditure (EE), body weight gain, and metabolic gene expression for 6 months. Gcn2 KO mice recapitulate this phenotype, but LP-induced effects on food intake, EE, and body weight subsequently begin to appear after 14 days on diet. We show that this delayed emergence of LP-induced metabolic effects in Gcn2 KO mice coincides with a delayed but progressive increase of hepatic Fgf21 expression and blood FGF21 concentrations over time. These data indicate that FGF21 is essential for the metabolic response to protein restriction but that GCN2 is only transiently required for LP-induced FGF21. PMID- 27396337 TI - Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer. AB - Breast cancer consists of at least five main molecular "intrinsic" subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression. PMID- 27396338 TI - An Atypical Tropomyosin in Drosophila with Intermediate Filament-like Properties. AB - A longstanding mystery has been the absence of cytoplasmic intermediate filaments (IFs) from Drosophila despite their importance in other organisms. In the course of characterizing the in vivo expression and functions of Drosophila Tropomyosin (Tm) isoforms, we discovered an essential but unusual product of the Tm1 locus, Tm1-I/C, which resembles an IF protein in some respects. Like IFs, Tm1-I/C spontaneously forms filaments in vitro that are intermediate in diameter between F-actin and microtubules. Like IFs but unlike canonical Tms, Tm1-I/C contains N- and C-terminal low-complexity domains flanking a central coiled coil. In vivo, Tm1-I/C forms cytoplasmic filaments that do not associate with F-actin or canonical Tms. Tm1-I/C is essential for collective border cell migration, in epithelial cells for proper cytoarchitecture, and in the germline for the formation of germ plasm. These results suggest that flies have evolved a distinctive type of cytoskeletal filament from Tm. PMID- 27396339 TI - Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development. AB - MLL-AF4+ infant B cell acute lymphoblastic leukemia is characterized by an early onset and dismal survival. It initiates before birth, and very little is known about the early stages of the disease's development. Using a conditional Mll-AF4 expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self renewal capacity during a putative pre-leukemic state. This occurs between embryonic days 12 and 14 and manifests itself most strongly in the lymphoid primed multipotent progenitor population, thus pointing to a window of opportunity and a potential cell of origin. However, this state alone is insufficient to generate disease, with the mice succumbing to B cell lymphomas only after a long latency. Future analysis of the molecular details of this pre leukemic state will shed light on additional events required for progression to acute leukemia. PMID- 27396340 TI - Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-beta Pathway. AB - In glioblastoma, invasion and proliferation are presumed to be mutually exclusive events; however, the molecular mechanisms that mediate this switch at the cellular level remain elusive. Previously, we have shown that phospho-OLIG2, a central-nervous-system-specific transcription factor, is essential for tumor growth and proliferation. Here, we show that the modulation of OLIG2 phosphorylation can trigger a switch between proliferation and invasion. Glioma cells with unphosphorylated OLIG2(S10, S13, S14) are highly migratory and invasive, both in vitro and in vivo. Mechanistically, unphosphorylated OLIG2 induces TGF-beta2 expression and promotes invasive mesenchymal properties in glioma cells. Inhibition of the TGF-beta2 pathway blocks this OLIG2-dependent invasion. Furthermore, ectopic expression of phosphomimetic Olig2 is sufficient to block TGF-beta2-mediated invasion and reduce expression of invasion genes (ZEB1 and CD44). Our results not only provide a mechanistic insight into how cells switch from proliferation to invasion but also offer therapeutic opportunities for inhibiting dissemination of gliomas. PMID- 27396342 TI - miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-beta-Induced Epithelial-to-Mesenchymal Transition. AB - Epithelial-to-mesenchymal transition (EMT) confers several traits to cancer cells that are required for malignant progression. Here, we report that miR-27b-3p mediated silencing of the single-strand RNA binding protein KHSRP is required for transforming growth factor beta (TGF-beta)-induced EMT in mammary gland cells. Sustained KHSRP expression limits TGF-beta-dependent induction of EMT factors and cell migration, whereas its knockdown in untreated cells mimics TGF-beta-induced EMT. Genome-wide sequencing analyses revealed that KHSRP controls (1) levels of mature miR-192-5p, a microRNA that targets a group of EMT factors, and (2) alternative splicing of a cohort of pre-mRNAs related to cell adhesion and motility including Cd44 and Fgfr2. KHSRP belongs to a ribonucleoprotein complex that includes hnRNPA1, and the two proteins cooperate in promoting epithelial type exon usage of select pre-mRNAs. Thus, TGF-beta-induced KHSRP silencing is central in a pathway leading to gene-expression changes that contribute to the cellular changes linked to EMT. PMID- 27396341 TI - Anti-Mullerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer. AB - Anti-Mullerian hormone (AMH) and its type II receptor AMHR2, both previously thought to primarily function in gonadal tissue, were unexpectedly identified as potent regulators of transforming growth factor (TGF-beta)/bone morphogenetic protein (BMP) signaling and epithelial-mesenchymal transition (EMT) in lung cancer. AMH is a TGF-beta/BMP superfamily member, and AMHR2 heterodimerizes with type I receptors (ALK2, ALK3) also used by the type II receptor for BMP (BMPR2). AMH signaling regulates expression of BMPR2, ALK2, and ALK3, supports protein kinase B-nuclear factor kappaB (AKT-NF-kappaB) and SMAD survival signaling, and influences BMP-dependent signaling in non-small cell lung cancer (NSCLC). AMH and AMHR2 are selectively expressed in epithelial versus mesenchymal cells, and loss of AMH/AMHR2 induces EMT. Independent induction of EMT reduces expression of AMH and AMHR2. Importantly, EMT associated with depletion of AMH or AMHR2 results in chemoresistance but sensitizes cells to the heat shock protein 90 (HSP90) inhibitor ganetespib. Recognition of this AMH/AMHR2 axis helps to further elucidate TGF-beta/BMP resistance-associated signaling and suggests new strategies for therapeutic targeting of EMT. PMID- 27396343 TI - Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes. AB - Growing evidence indicates important roles for astrocytes in neurodevelopment and diseases. However, astrocytes and their roles in these processes remain poorly understood. Despite recent progress in reprogramming somatic cells into different types of neural cells, reprogramming to astrocytes has lagged. Here, we show that functional astrocytes can be generated from mammalian fibroblasts using only small molecules. Induced mouse astrocytes resemble primary astrocytes in astrocytic gene expression and epigenomic status and exhibit functional properties in promoting neuronal maturation, glutamate uptake, and calcium signaling. Moreover, these cells can recapitulate the Alexander disease phenotype of protein aggregation when expressing Gfap with a disease-causing mutation. The same compounds can also reprogram human fibroblasts into astroglial progenitor cells that can further mature into functional astrocytes. These chemically induced astrocytes may provide cellular models to uncover roles of astrocytes in normal neurodevelopment and pathogenesis of neurological diseases. PMID- 27396344 TI - Is Being Insured Sufficient to Ensure Effective Access to Health Care among Poor People in Mexico in the Long Term? PMID- 27396345 TI - Mice are not Men: ADAM30 Findings Emphasize a Broader Look Towards Murine Alzheimer's Disease Models. PMID- 27396346 TI - Neuroprotective effect and mechanism of Mu-Xiang-You-Fang on cerebral ischemia reperfusion injury in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The present study is to investigate the neuroprotective effect of Mu-Xiang-You-Fang (MXYF), a classic Traditional Chinese Medicine used by Chinese minorities to treat stroke, on cerebral ischemia reperfusion (I/R) injury and the related signaling pathways. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 6 groups: sham group, I/R group, nimodipine and MXYF (58, 116 and 232mg/kg respectively) groups. Cerebral ischemia model was induced by middle cerebral artery occlusion for 2h followed by reperfusion for 48h. Neurological functional score was evaluated according to the method of Zea longa's score and the infarct area was determined by 2,3,5 triphenyltetrazolium chloride (TTC) staining at 48h after reperfusion. The protein expression of cytochrome c (cyt-c), Bcl-2, Bax, caspase-9, caspase-3 and caspase-7 were analyzed by western blot and the mRNA expression of Caspase-9, Caspase-3 and Caspase-7 were determined by the reverse transcription-polymerase chain reaction. RESULTS: Oral administration of MXYF (116 and 232mg/kg) significantly reduced the neurological functional score and attenuated the cerebral infarct area. Western blot analysis showed that the expression of Bcl-2 is enhanced and Bax expression is inhibited after treatment with MXYF (116 and 232mg/kg), leading to significant increase of the ratio between Bcl-2 and Bax. Furthermore, the protein expression of cyt-c, caspase-9, caspase-3 and caspase-7 was significantly inhibited while the mRNA expression of caspase-9, caspase-3 and caspase-7 but not cyt-c was markedly inhibited in the MXYF (116 and 232mg/kg) treatment groups compared with the I/R group. CONCLUSIONS: The above data suggested that MXYF has potential neuroprotective activities by the regulation of apoptotic pathway, MXYF is a promising agent in treatment of stroke. PMID- 27396347 TI - Toxicological evaluation of the flavonoid-rich extract from Maydis stigma: Subchronic toxicity and genotoxicity studies in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Maydis stigma (corn silk) has a long history of use as a traditional herbal medicine or functional food in China and many other countries and has been listed in the Chinese Pharmacopea. However, little data about its potential toxicity is available. AIM OF THE STUDY: In this study, we evaluated the subchronic toxicity and genotoxicity of the flavonoid-rich extract from Maydis stigma (FMS) in mice. MATERIALS AND METHODS: In the subchronic toxicity study, the FMS was administered orally to mice at doses of 2.50, 5.00 and 10.00g/kg/day for 28 consecutive days. At the end of experiment, general clinical signs, mortality, haematological, biochemical and histopathological parameters were examined. The genotoxicity of FMS was also evaluated by the micronucleus assay and the sperm malformation assay. RESULTS: All animals survived until the scheduled necropsy, and no statistically significant or toxicologically relevant differences were observed in any of the FMS-treatment groups, compared with the control group. The no-observed-adverse-effect level (NOAEL) was determined as 10.00g/kg/day. Based on the results of the micronucleus assay and the sperm malformation assay, no evidence of genotoxicity was found either in somatic cells or germ cells even at an experimental upper limit dose (10.00g/kg/day). CONCLUSIONS: The results of the present studies might support the safe use of FMS as a functional food, food additive and natural remedy. PMID- 27396349 TI - Antiplasmodial activities of a Thai traditional antipyretic formulation, Bencha Loga-Wichian: A comparative study between the roots and their substitutes, the stems. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bencha-Loga-Wichian (BLW) is a polyherbal antipyretic formulation that is comprised of Capparis micracantha, Clerodendrum indicum, Ficus racemosa, Harrisonia perforata, and Tiliacora triandra. A traditional medical textbook has documented the use of this formulation for the treatment of many types of fever, including malaria-like fever. Traditionally, BLW is composed of the root parts of those plants. However, in current practice, the stem parts are frequently substituted. Thus, this study aimed to evaluate the antiplasmodial activities of BLW and compare the efficacy between the stem and root parts. MATERIALS AND METHODS: BLW formulations produced from either the stem or root parts of the various constituent plants as well as the stems or roots of the individual plants were separately extracted and tested against the chloroquine-sensitive (Pf3D7) and -resistant (PfW2) strains Plasmodium falciparum using flow cytometry. The cytotoxicity against peripheral blood mononuclear cells was evaluated using the WST-8 assay to determine the selectivity index (SI). The active compounds of BLW were isolated using antiplasmodial-guided isolation and quantified using Ultra-Performance Liquid Chromatography (UPLC). RESULTS: The stem and root parts of BLW and the individual plants exhibited antiplasmodial activities at the same levels with good SI values in the range of 3.55-19.74. The extracts of BLW exhibited promising antiplasmodial activity against both Pf3D7 (IC50<5ug/mL) and PfW2 (IC50=6-10ug/mL). Among the five component plants, T. triandra was the most active and exhibited an IC50<5ug/mL against both strains of parasites with SI values >10. We isolated tiliacorinine and yanangcorinine as the major active compounds (IC50<2ug/mL). However, these two compounds demonstrated cytotoxic effects (SI<1). The UPLC analysis identified these compounds in both the stem and root parts of BLW in the range of 0.57-7.66%, which correlated with the antiplasmodial activity. The concentrations of these compounds in BLW, at comparable efficacy, were much less than those at the IC50s for the single compounds alone. It suggested that synergistic interactions increased the antiplasmodial effects as well as alleviated the toxicity of the active compounds in BLW. CONCLUSION: This study described a promising antiplasmodial activity of BLW that had good selectivity and a toxicity-alleviating effect. The results provided scientific support for the use of this formulation for the treatment of malaria. In addition, the stem and root parts of the plants in BLW exhibited equivalent activities, which indicates the potential for the substitution of the stem parts in the formulation. Thus, we recommend additional study of the stem parts of these plants for further development on the basis of the availability and sustainability. PMID- 27396348 TI - Piper umbellatum L.: A medicinal plant with gastric-ulcer protective and ulcer healing effects in experimental rodent models. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed. MATERIALS AND METHODS: The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA+ and vacA+ strain. The probable mechanism of action of HEPu was evaluated by determining gastric secretory parameters, antioxidant enzyme (catalase), non-protein sulfhydryl (glutathione) and malondialdehyde levels in gastric tissue, including pro-inflammatory (IL 1beta, TNF-a, IL -17, RANTES, IFN-gamma and MIP-2) and anti-inflammatory (IL-10) cytokines. RESULTS: HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity. CONCLUSION: The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is independent of anti-H. pylori activity, with substances probably responsible for the pharmacological activity being flavonoids, quercetin and rutin. These results support the popular use of P. umbellatum leaves in the treatment of peptic ulcers. PMID- 27396350 TI - Study on material base and action mechanism of compound Danshen dripping pills for treatment of atherosclerosis based on modularity analysis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been widely used in China and its surrounding countries in clinical treatments for centuries-long time. However, due to the complexity of TCM constituents, both action mechanism and material base of TCM remain nearly unknown. AIM OF THE STUDY: The present study was designed to uncover the action mechanism and material base of TCM in a low-cost manner. MATERIALS AND METHODS: Compound Danshen dripping pills (DSP) is a widely used TCM for treatment of atherosclerosis, and was researched here to demonstrate the effectiveness of our method. We constructed a heterogeneous network for DSP, identified the significant network module, and analyzed the primary pharmacological units by performing GO and pathways enrichment analysis. RESULTS: Two significant network modules were identified from the heterogeneous network of DSP, and three compounds out of four hub nodes in the network were found to intervene in the process of atherosclerosis. Moreover, 13 out of 20 enriched pathways that were ranked in top 10 corresponding to both the two pharmacological units were found to be involved in the process of atherosclerosis. CONCLUSIONS: Quercetin, luteolin and apigenin may be the main active compounds which modulate the signaling pathways, such as metabolism of xenobiotics by cytochrome P450, retinol metabolism, etc. The present method helps reveal the action mechanism and material base of DSP for treatment of atherosclerosis. PMID- 27396351 TI - Paridis Rhizoma Sapoinins attenuates liver fibrosis in rats by regulating the expression of RASAL1/ERK1/2 signal pathway. AB - ETHNO-PHARMACOLOGICAL RELEVANCE: Paridis Rhizoma is a Chinese medicinal herb that has been used in liver disease treatment for thousands of years. Our previous studies found that Paridis Rhizoma saponins (PRS) are the critical components of Paridis Rhizoma which has good liver protection effect. However, the anti-hepatic fibrosis effect and the mechanism of PRS have seldom been reported. AIM OF THE STUDY: To investigate the potential of PRS in the treatment of experimental liver fibrosis and the underlying mechanism. MATERIALS AND METHODS: The chemical feature fingerprint of PRS was analyzed by UPLC-PDA. A total of 40 Male Sprague Dawley (SD) rats were randomly divided into the control group, the model group, the PRS high dose group (PRS H) and the PRS low dose group (PRS L) with 10 rats in each group. The model, PRS H and L groups as liver fibrosis models were established with carbon tetrachloride (CCl4) method. PRS H and L groups were adopted PRS (300 and 150mg/kgd-1) treatment since the twelfth week of modeling till the sixteenth week. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and MASSON trichrome staining. Immunohistochemical analysis was performed to determine the protein expression of the RASAL1. RT-PCR and western blotting were used to detect the expression of ERK1/2 mRNA and protein. RESULTS: Four saponins in PRS were identified from 19 detected chromatographic peaks on UPLC-PDA by comparing to the standard compounds. PRS can improve the degeneration and necrosis of hepatic tissue, reduce the extent of its fibrous hyperplasia according to H&E and MASSON staining detection. As was detected in PRS H and L groups, PRS down-regulated p-ERK1/2 mRNA and RASAL1 protein, and up-regulated the level of p-ERK1/2 mRNA and RASAL1 protein. CONCLUSION: These results demonstrated that PRS can attenuate CCl4 induced liver fibrosis through the regulation of RAS/ERK1/2 signal pathway. PMID- 27396352 TI - Identification of the novel HLA-B*15:02:11 allele in a Chinese individual. AB - The novel allele B*15:02:11, was identified in a Chinese individual by sequence based typing. PMID- 27396353 TI - Loss of microRNA-145 expression is involved in the development and prognosis of breast cancer complicated by type 2 diabetes mellitus. AB - OBJECTIVE: To explore the relationships of the expression of miR-145 to the clinicopathological characteristics and prognosis of patients with breast cancer complicated by type 2 diabetes mellitus (T2DM). METHODS: A total of 257 female patients with breast cancer were enrolled for our experiment, including 140 patients with simple breast cancer (control group) and 117 patients with breast cancer complicated by T2DM (observation group). Patients were treated with modified radical mastectomy supplemented with radiotherapy, chemotherapy and endocrine therapy. qRT-PCR was used for the detection of miR-145 expression in patients of both groups. Follow-up lasted 13-60 months. RESULTS: The relative expression of miR-145 in the observation group was significantly lower than that in the control group (p<0.05). The expression of miR-145 in patients with breast cancer complicated by T2DM was related to the history of diabetes, tumor node metastasis (TNM) stage, tumor size, lymph node metastasis (LNM), estrogen receptor (ER) status, and HER2 (all p<0.05). The median disease-free survival (DFS) was significantly longer and the 5-year DFS rate significantly higher in the high-expression group than in the low-expression group. History of diabetes, TNM stage, tumor size, LNM, ER status, and HER2 were risk factors for patients with breast cancer complicated by T2DM (all p<0.05). CONCLUSIONS: Loss of miR-145 expression is related to the development of breast cancer complicated by T2DM, and low miR-145 expression might be an adverse prognostic factor in patients with this disease. PMID- 27396354 TI - Synergistic association of CYP1A1 polymorphisms with increased susceptibility to squamous cell lung cancer in north Indian smokers. AB - OBJECTIVES: Studies in different populations have shown that polymorphisms within the CYP1A1 gene play an important role in determining individual susceptibility to lung cancer. However, the data obtained so far have been contradictory within the same or different populations. Few studies have focused on the synergistic effect of CYP1A1 polymorphisms on the susceptibility to lung cancer overall and to different histological subtypes along with the impact of smoking. METHODS: A total of 704 individuals (353 lung cancer patients and 351 controls) were evaluated for CYP1A1 polymorphisms. CYP1A1 genotyping was done by means of PCR RFLP. RESULTS: A CYP1A1 mutant genotype was found to be significantly associated with lung cancer (OR = 3.15; 95% CI = 1.75-5.71; p = 0.0001) and this risk was 4 fold higher in case of squamous cell carcinoma (SCC). The CYP1A1 m2 allelic variant was found to be strongly associated with the risk of SCC and adenocarcinoma. The combined "at risk" genotypes of the CYP1A1 m1 and m2 allelic variants were associated with lung cancer risk and this risk was higher in case of SCC (OR = 2.0; 95% CI = 1.97-3.81; p = 0.028). Furthermore, the lung cancer risk was associated with smoking, especially in heavy smokers carrying CYP1A1 variant genotypes. We also observed that heavy smokers with the mutant m1 genotype were at increased risk of SCC (OR = 5.4; 95% CI = 2.4-11.9; p<0.0001). Furthermore, when stratified for smoking dose and histology, the effect was compounded in heavy smokers and SCC (OR = 7.5; 95% CI = 1.8-30.9; p = 0.004). CONCLUSIONS: Polymorphism in the CYP1A1 gene is an important risk modifier for lung cancer. PMID- 27396355 TI - Metabolic engineering of Yarrowia lipolytica to produce chemicals and fuels from xylose. AB - Yarrowia lipolytica is a biotechnological chassis for the production of a range of products, such as microbial oils and organic acids. However, it is unable to consume xylose, the major pentose in lignocellulosic hydrolysates, which are considered a preferred carbon source for bioprocesses due to their low cost, wide abundance and high sugar content. Here, we engineered Y. lipolytica to metabolize xylose to produce lipids or citric acid. The overexpression of xylose reductase and xylitol dehydrogenase from Scheffersomyces stipitis were necessary but not sufficient to permit growth. The additional overexpression of the endogenous xylulokinase enabled identical growth as the wild type strain in glucose. This mutant was able to produce up to 80g/L of citric acid from xylose. Transferring these modifications to a lipid-overproducing strain boosted the production of lipids from xylose. This is the first step towards a consolidated bioprocess to produce chemicals and fuels from lignocellulosic materials. PMID- 27396356 TI - In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs). AB - BACKGROUND: Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. METHODS: To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1 hBMECs). To determine whether 2-PAM is a substrate for common brain efflux pumps, experiments were performed in the MDCKII-MDR1 cell line, transfected to overexpress the P-gp efflux pump, and the MDCKII-FLuc-ABCG2 cell line, transfected to overexpress the BCRP efflux pump. To determine how transcellular transport influences enzyme reactivation, we developed a modified transwell assay where the inhibited acetylcholinesterase enzyme, substrate, and reporter are introduced into the basolateral chamber. Enzymatic activity was inhibited using paraoxon and parathion. RESULTS: The permeability of 2-PAM is about 2 * 10(-6) cm s(-1) in MDCK cells and about 1 * 10(-6) cm s(-1) in BC1-hBMECs. Permeability is not influenced by pre-treatment with atropine. In addition, 2-PAM is not a substrate for the P-gp or BCRP efflux pumps. CONCLUSIONS: The low permeability explains poor brain penetration of 2-PAM and therefore the slow enzyme reactivation. This elucidates one of the reasons for the necessity of sustained intravascular (IV) infusion in response to organophosphate poisoning. PMID- 27396357 TI - Bayesian inference for age-structured population model of infectious disease with application to varicella in Poland. AB - The dynamics of the infectious disease transmission are often best understood by taking into account the structure of population with respect to specific features, for example age or immunity level. The practical utility of such models depends on the appropriate calibration with the observed data. Here, we discuss the Bayesian approach to data assimilation in the case of a two-state age structured model. Such models are frequently used to explore the disease dynamics (i.e. force of infection) based on prevalence data collected at several time points. We demonstrate that, in the case when the explicit solution to the model equation is known, accounting for the data collection process in the Bayesian framework allows us to obtain an unbiased posterior distribution for the parameters determining the force of infection. We further show analytically and through numerical tests that the posterior distribution of these parameters is stable with respect to a cohort approximation (Escalator Boxcar Train) of the solution. Finally, we apply the technique to calibrate the model based on observed sero-prevalence of varicella in Poland. PMID- 27396358 TI - A dynamical model for bark beetle outbreaks. AB - Tree-killing bark beetles are major disturbance agents affecting coniferous forest ecosystems. The role of environmental conditions on driving beetle outbreaks is becoming increasingly important as global climatic change alters environmental factors, such as drought stress, that, in turn, govern tree resistance. Furthermore, dynamics between beetles and trees are highly nonlinear, due to complex aggregation behaviors exhibited by beetles attacking trees. Models have a role to play in helping unravel the effects of variable tree resistance and beetle aggregation on bark beetle outbreaks. In this article we develop a new mathematical model for bark beetle outbreaks using an analogy with epidemiological models. Because the model operates on several distinct time scales, singular perturbation methods are used to simplify the model. The result is a dynamical system that tracks populations of uninfested and infested trees. A limiting case of the model is a discontinuous function of state variables, leading to solutions in the Filippov sense. The model assumes an extensive seed bank so that tree recruitment is possible even if trees go extinct. Two scenarios are considered for immigration of new beetles. The first is a single tree stand with beetles immigrating from outside while the second considers two forest stands with beetle dispersal between them. For the seed-bank driven recruitment rate, when beetle immigration is low, the forest stand recovers to a beetle-free state. At high beetle immigration rates beetle populations approach an endemic equilibrium state. At intermediate immigration rates, the model predicts bistability as the forest can be in either of the two equilibrium states: a healthy forest, or a forest with an endemic beetle population. The model bistability leads to hysteresis. Interactions between two stands show how a less resistant stand of trees may provide an initial toe-hold for the invasion, which later leads to a regional beetle outbreak in the resistant stand. PMID- 27396359 TI - Identification of thermophilic proteins by incorporating evolutionary and acid dissociation information into Chou's general pseudo amino acid composition. AB - Thermophilic proteins can thrive stalely at the high temperatures. Identification of thermophilic protein could be helpful to learn the function of protein. Automated prediction of thermophilic protein is an important tool for genome annotation. In this work, a powerful predictor is proposed by combining amino acid composition, evolutionary information, and acid dissociation constant. The overall prediction accuracy of 93.53% was obtained for using the algorithm of support vector machine. In order to check the performance of our method, two low similarity independent testing datasets are used to test the proposed method. Comparisons with other methods show that the prediction results were better than other existing methods in literature. This indicates that our approach was effective to predict thermophilic proteins. PMID- 27396360 TI - Mathematical study on robust tissue pattern formation in growing epididymal tubule. AB - Tissue pattern formation during development is a reproducible morphogenetic process organized by a series of kinetic cellular activities, leading to the building of functional and stable organs. Recent studies focusing on mechanical aspects have revealed physical mechanisms on how the cellular activities contribute to the formation of reproducible tissue patterns; however, the understanding for what factors achieve the reproducibility of such patterning and how it occurs is far from complete. Here, I focus on a tube pattern formation during murine epididymal development, and show that two factors influencing physical design for the patterning, the proliferative zone within the tubule and the viscosity of tissues surrounding to the tubule, control the reproducibility of epididymal tubule pattern, using a mathematical model based on experimental data. Extensive numerical simulation of the simple mathematical model revealed that a spatially localized proliferative zone within the tubule, observed in experiments, results in more reproducible tubule pattern. Moreover, I found that the viscosity of tissues surrounding to the tubule imposes a trade-off regarding pattern reproducibility and spatial accuracy relating to the region where the tubule pattern is formed. This indicates an existence of optimality in material properties of tissues for the robust patterning of epididymal tubule. The results obtained by numerical analysis based on experimental observations provide a general insight on how physical design realizes robust tissue pattern formation. PMID- 27396361 TI - Recovery From Exercise-Induced Muscle Damage: Cold-Water Immersion Versus Whole Body Cryotherapy. AB - PURPOSE: To compare the effects of cold-water immersion (CWI) and whole-body cryotherapy (WBC) on recovery kinetics after exercise-induced muscle damage. METHODS: Ten physically active men performed single-leg hamstring eccentric exercise comprising 5 sets of 15 repetitions. Immediately postexercise, subjects were exposed in a randomized crossover design to CWI (10 min at 10 degrees C) or WBC (3 min at -110 degrees C) recovery. Creatine kinase concentrations, knee flexor eccentric (60 degrees /s) and posterior lower-limb isometric (60 degrees ) strength, single-leg and 2-leg countermovement jumps, muscle soreness, and perception of recovery were measured. The tests were performed before and immediately, 24, 48, and 72 h after exercise. RESULTS: Results showed a very likely moderate effect in favor of CWI for single-leg (effect size [ES] = 0.63; 90% confidence interval [CI] = -0.13 to 1.38) and 2-leg countermovement jump (ES = 0.68; 90% CI = -0.08 to 1.43) 72 h after exercise. Soreness was moderately lower 48 h after exercise after CWI (ES = -0.68; 90% CI = -1.44 to 0.07). Perception of recovery was moderately enhanced 24 h after exercise for CWI (ES = 0.62; 90% CI = -1.38 to 0.13). Trivial and small effects of condition were found for the other outcomes. CONCLUSIONS: CWI was more effective than WBC in accelerating recovery kinetics for countermovement-jump performance at 72 h postexercise. CWI also demonstrated lower soreness and higher perceived recovery levels across 24-48 h postexercise. PMID- 27396363 TI - N(6)-Methyladenosine RNA Modification Regulates Shoot Stem Cell Fate in Arabidopsis. AB - N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification on mRNA and requires a multicomponent m(6)A methyltransferase complex in mammals. How their plant counterparts determine the global m(6)A modification landscape and its molecular link to plant development remain unknown. Here we show that FKBP12 INTERACTING PROTEIN 37 KD (FIP37) is a core component of the m(6)A methyltransferase complex, which underlies control of shoot stem cell fate in Arabidopsis. The mutants lacking FIP37 exhibit massive overproliferation of shoot meristems and a transcriptome-wide loss of m(6)A RNA modifications. We further demonstrate that FIP37 mediates m(6)A RNA modification on key shoot meristem genes inversely correlated with their mRNA stability, thus confining their transcript levels to prevent shoot meristem overproliferation. Our results suggest an indispensable role of FIP37 in mediating m(6)A mRNA modification, which is required for maintaining the shoot meristem as a renewable source for continuously producing all aerial organs in plants. PMID- 27396362 TI - KIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses. AB - Autophagy is a cellular degradation process important for neuronal development and survival. Neurons are highly polarized cells in which autophagosome biogenesis is spatially compartmentalized. The mechanisms and physiological importance of this spatial compartmentalization of autophagy in the neuronal development of living animals are not well understood. Here we determine that, in Caenorhabditis elegans neurons, autophagosomes form near synapses and are required for neurodevelopment. We first determine, through unbiased genetic screens and systematic genetic analyses, that autophagy is required cell autonomously for presynaptic assembly and for axon outgrowth dynamics in specific neurons. We observe autophagosome biogenesis in the axon near synapses, and this localization depends on the synaptic vesicle kinesin, KIF1A/UNC-104. KIF1A/UNC 104 coordinates localized autophagosome formation by regulating the transport of the integral membrane autophagy protein, ATG-9. Our findings indicate that autophagy is spatially regulated in neurons through the transport of ATG-9 by KIF1A/UNC-104 to regulate neurodevelopment. PMID- 27396365 TI - Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage. AB - The limitations associated with the clinical utility of conventional platinum anticancer drugs have stimulated research leading to the design of new metallodrugs with improved pharmacological properties, particularly with increased selectivity for cancer cells. Very recent research has demonstrated that photoactivation or photopotentiation of platinum drugs can be one of the promising approaches to tackle this challenge. This is so because the application of irradiation can be targeted exclusively to the tumor tissue so that the resulting effects could be much more selective and targeted to the tumor. We show in this work that the presence of 1-methyl-7-azaindole in trans-[PtCl2(NH3)(L)] (L = 1-methyl-7-azaindole, compound 1) markedly potentiated the DNA binding ability of 1 when irradiated by UVA light in a cell-free medium. Concomitantly, the formation of cytotoxic bifunctional cross-links was markedly enhanced. In addition, 1, when irradiated with UVA, was able to effectively cleave the DNA backbone also in living cells. The incorporation of 1-methyl-7-azaindole moiety had also a profound effect on the photophysical properties of 1, which can generate singlet oxygen responsible for the DNA cleavage reaction. Finally, we found that 1, upon irradiation with UVA light, exhibited a pronounced dose dependent decrease in viability of A2780 cells whereas it was markedly less cytotoxic if the cells were treated in the absence of light. Hence, it is possible to conclude that 1 is amenable to photodynamic therapy. PMID- 27396364 TI - Mass spectrometric immunoassays for discovery, screening and quantification of clinically relevant proteoforms. AB - Human proteins can exist as multiple proteoforms with potential diagnostic or prognostic significance. MS top-down approaches are ideally suited for proteoforms identification because there is no prerequisite for a priori knowledge of the specific proteoform. One such top-down approach, termed mass spectrometric immunoassay utilizes antibody-derivatized microcolumns for rapid and contained proteoforms isolation and detection via MALDI-TOF MS. The mass spectrometric immunoassay can also provide quantitative measurement of the proteoforms through inclusion of an internal reference standard into the analytical sample, serving as normalizer for all sample processing and data acquisition steps. Reviewed here are recent developments and results from the application of mass spectrometric immunoassays for discovery of clinical correlations of specific proteoforms for the protein biomarkers RANTES, retinol binding protein, serum amyloid A and apolipoprotein C-III. PMID- 27396366 TI - Cerebral Sinovenous Thrombosis in Neonates and Children. AB - Investigators from Erasmus University Hospital in Belgium and Gustave-Dron Hospital and Roger-Salengro Hospital in France studied the clinical and neuroradiologic characteristics of cerebral sinovenous thrombosis (CSVT) in neonates and children. PMID- 27396367 TI - The adaptive drop foot stimulator - Multivariable learning control of foot pitch and roll motion in paretic gait. AB - Many stroke patients suffer from the drop foot syndrome, which is characterized by a limited ability to lift (the lateral and/or medial edge of) the foot and leads to a pathological gait. In this contribution, we consider the treatment of this syndrome via functional electrical stimulation (FES) of the peroneal nerve during the swing phase of the paretic foot. A novel three-electrodes setup allows us to manipulate the recruitment of m. tibialis anterior and m. fibularis longus via two independent FES channels without violating the zero-net-current requirement of FES. We characterize the domain of admissible stimulation intensities that results from the nonlinearities in patients' stimulation intensity tolerance. To compensate most of the cross-couplings between the FES intensities and the foot motion, we apply a nonlinear controller output mapping. Gait phase transitions as well as foot pitch and roll angles are assessed in realtime by means of an Inertial Measurement Unit (IMU). A decentralized Iterative Learning Control (ILC) scheme is used to adjust the stimulation to the current needs of the individual patient. We evaluate the effectiveness of this approach in experimental trials with drop foot patients walking on a treadmill and on level ground. Starting from conventional stimulation parameters, the controller automatically determines individual stimulation parameters and thus achieves physiological foot pitch and roll angle trajectories within at most two strides. PMID- 27396368 TI - Thrombopoietic cytokines in patients with hepatitis C virus-associated immune thrombocytopenia. AB - OBJECTIVES: Complex and multiple mechanisms are involved in the etiology of Hepatitis C virus-associated immune thrombocytopenia (HCV-ITP). Many hematopoietic growth factors affect the thrombopoiesis. The aim of this study was to clarify the interaction of the thrombopoietic factors in patients with HCV ITP. METHODS: We selected 33 patients with HCV-ITP and 17 normal individuals. We compare serum interleukin (IL)-3, IL-6, IL-11, thrombopoietin (Tpo), stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNFalpha), and spleen size between these two groups. RESULTS: Our study shows that Tpo, IL-6, and TNFalpha significantly increased in patients with HCV-ITP compared to the normal population (Tpo:122.577 vs. 40.602; IL-6: 2.175 vs. 0.943; TNFalpha: 2.460 vs. 1.322). IL-11 was significantly lower in the HCV-ITP group (10.829 vs. 15.042). HCV-ITP patients had a higher spleen index (21.121 vs 13.498, P = 0.003). According to regression analysis and multiple linear regression analysis, only IL-11 had a significantly positive correlation with platelet count, while TNFalpha showed a negative correlation. DISCUSSIONS: Tpo and IL-6 increased in patients with HCV-ITP, suggesting a positive feedback of low platelet count. TNFalpha-associated immune response is suspected to have an impact on low platelet count. IL-11 is assumed to directly affect thrombopoiesis. CONCLUSIONS: This study is the most comprehensive study to evaluate the interaction between platelet count and the important thrombopoetic factors in patients with HCV-ITP. The thrombopoietic factors clearly play an important role in HCV-ITP. PMID- 27396369 TI - A novel method for automated tracking and quantification of adult zebrafish behaviour during anxiety. AB - BACKGROUND: Behavioural neuroscience relies on software driven methods for behavioural assessment, but the field lacks cost-effective, robust, open source software for behavioural analysis. NEW METHOD: Here we propose a novel method which we called as ZebraTrack. It includes cost-effective imaging setup for distraction-free behavioural acquisition, automated tracking using open-source ImageJ software and workflow for extraction of behavioural endpoints. Our ImageJ algorithm is capable of providing control to users at key steps while maintaining automation in tracking without the need for the installation of external plugins. RESULTS: We have validated this method by testing novelty induced anxiety behaviour in adult zebrafish. Our results, in agreement with established findings, showed that during state-anxiety, zebrafish showed reduced distance travelled, increased thigmotaxis and freezing events. Furthermore, we proposed a method to represent both spatial and temporal distribution of choice-based behaviour which is currently not possible to represent using simple videograms. COMPARISON WITH EXISTING METHOD(S): ZebraTrack method is simple and economical, yet robust enough to give results comparable with those obtained from costly proprietary software like Ethovision XT. CONCLUSION: We have developed and validated a novel cost-effective method for behavioural analysis of adult zebrafish using open-source ImageJ software. PMID- 27396370 TI - Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/ Refractory Diffuse Large B Cell Lymphoma. AB - Since the improvement of chemotherapy and innovation of rituximab, about 60% of patients with diffuse large B cell lymphoma (DLBCL) could receive long-term survival after firstline therapy. Around 30% fail to respond or experience relapse considered as the relapsed/refractory DLBCL, the highdose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) has been used as the second-line treatment. However, the patients relapse after auto HSCT or not eligible for the auto-HSCT have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the potentially curative way in such kind of patients. In this paper, we collected the published data about patients with relapsed/refractory DLBCL who underwent allo-HSCT, demonstrated the appropriate candidate for allo-HSCT, identified the effect of the donor types on the recipients, presented the major conditioning regimens for allo-HSCT and figured out the outcomes of each conditioning regimen. We also tried to identify the prognostic factors on the outcome which might shed some light on the further clinical application. PMID- 27396371 TI - DIFFERENTIAL PROTEOME ANALYSIS OF THE MALE AND FEMALE ANTENNAE FROM Holotrichia parallela. AB - To understand the olfactory mechanisms of Holotrichia parallela antennae in detecting volatile compounds in the environment, protein profiles of H. parallela antennae were analyzed using two-dimensional electrophoresis followed by mass spectrometry and bioinformatics analyses. Approximately 1,100 protein spots in silver staining gel were detected. Quantitative image analysis revealed that in total 47 protein spots showed significant changes in different genders of adult antennae. Thirty-five differentially expressed proteins were identified by Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI TOF/TOF) tandem mass spectrometer, among which 65.7% are involved in carbohydrate and energy metabolism, antioxidant system, transport, and amino acid/nucleotide metabolism. Some proteins identified here have not been reported previously in insect antennae. Identified male-biased proteins included odorant-binding protein 4, pheromone-binding protein-related protein 2, odorant-binding protein 14, prophenoloxidase-I, acyl-CoA dehydrogenase, aldo-keto reductase-like, carbamoyl phosphate synthetase, etc. whereas some proteins are female biased, such as antennae-rich cytochrome P450, aldehyde dehydrogenase, and putative glutamine synthetase. Alterations in the levels of some proteins were further confirmed by real time polymerase chain reaction (RT-PCR). The proteomic resources displayed here are valuable for the discovery of proteins from H. parallela antennae. PMID- 27396372 TI - Immunoglobulin A deficiency following treatment with lamotrigine. AB - Lamotrigine (LTG) is an anti-epileptic drug and mood-stabilizing agent, whose adverse effects include skin rash and dizziness. Interactions with the immune system are rare, and only a few cases linking hypogammaglobulinemia to LTG treatment have been previously described. In this report, we describe a case in which a patient developed hypogammaglobulinemia, and a subsequent immunoglobulin A (IgA) deficiency, following LTG treatment. As a result of her immunodeficiency, the patient presented with a severe urinary tract infection and required intravenous immunoglobulin. Serum levels of immunoglobulin G and M had recovered by seven months and one month after the discontinuation of LTG, respectively; however, IgA levels remained low (less than 4mg/dL) two years post-treatment. While previous reports have demonstrated IgA deficiencies in patients prescribed other antiepileptic drugs, this is the first case of an IgA deficiency following LTG administration. PMID- 27396373 TI - Functions of Ghrelin in Brain, Gut and Liver. AB - Ghrelin production occurs in the gastrointestinal tract with the greatest concentration in the fundus of the stomach, which accounts for approximately 75- 80% of circulating ghrelin levels. Desacyl ghrelin has been suggested to be involved in the regulation of energy homeostasis because of its ability to cross the blood-brain barrier and to induce increased neuronal activity in the hypothalamic arcuate nucleus. The enzyme called ghrelin O-acyl transferase is able to acylate ghrelin and regulates the physiological functions of the final peptide acyl ghrelin. The acylated ghrelin has an anti-inflammatory function that depends on its direct effect on T lymphocytes and monocytes, in which it inhibits the expression of proinflammatory cytokines such as Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), and Tumor Necrosis Factor (TNF-alpha). Some studies conducted in animal models show that ghrelin treatment reduces the amount of fibrogenic cells. In particular, ghrelin treatment decreases alpha -SMA protein expression, hepatic content of hydroxyproline and reduces the elevation of serum aspartate aminotransferase levels. Moreover, ghrelin attenuates liver injury and collagen deposition through inhibition of hepatic cell apoptosis and antioxidative activity, at least in part by nitric oxide induction. Several studies suggest that the orexigenic action of ghrelin is mediated via the neuropeptide Y neurons in the arcuate nucleus. Neuropeptide Y overexpression in the dorsomedial hypothalamus can cause hyperphagia and obesity in rat, which in turn causes liver steatosis, inflammation and fibrosis. The aims of this review were to examine and discuss the different functions of this hormone, particularly those that link the brain, gut and liver. PMID- 27396374 TI - Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system. AB - Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential. Twenty-four healthy male MU-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BPND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BPND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BPND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D2 /D3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D2 /D3 receptors may hint at an addiction relevant trait. PMID- 27396375 TI - Preoperative statin use is not associated with improvement in survival after glioblastoma surgery. AB - Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N=284) were followed up for a median of 18.1months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26; p=0.68) and after propensity score matching (HR 0.95, 95% CI 0.67 1.35; p=0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70-1.22; p= 0.73) and after propensity score matching (HR 1.13, 95% CI 0.78-1.64; p=0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients. PMID- 27396376 TI - rhBMP-2 protects against reoperation for pseudoarthrosis and/or instrumentation failure: A matched case-control study of 448 patients. AB - The objective of this independent study is to determine the impact of recombinant human bone morphogenetic protein 2 (rhBMP-2) on reoperation for pseudarthrosis and/or instrumentation failure. A nested case-control study of first-time posterolateral, instrumented fusion of the lumbar spine for degenerative spinal disease was undertaken. Cases of reoperation for pseudoarthrosis and/or instrumentation failure were assigned to controls, who did not experience the primary outcome measure at the time of reoperation. Cases and controls were matched on number of interspaces fused and inclusion of interbody. Predictors of reoperation for pseudoarthrosis and/or instrumentation failure were assessed with a conditional logistical regression controlling for rhBMP-2, age, obesity, and smoking. Of the 448 patients, 155 cases of reoperation for pseudoarthrosis and/or instrumentation were matched with 293 controls. Twenty-six percent of first-time surgeries included rhBMP-2, which was statistically more commonly used in the control cohort (33.11%) versus the case cohort (12.90%) (Unadjusted odds ratio [ORunadj]=0.28) (95% confidence interval [CI]: 0.16-0.49). Following a multivariate analysis controlling for age, obesity, and smoking, the rhBMP-2 recipients incurred a 73% lower odds of reoperation for pseudoarthrosis and/or instrumentation failure (95% CI, 0.15-0.48). Neither sarcomatous nor osseous neoplasm was detected in the study population. Mean follow up did not differ between the cases (81.57+/-standard deviation [SD] 4.98months) versus controls (74.75+/-2.49month) (ORunadj=1.01) (95% CI: 1.00-1.01). rhBMP-2 in lumbar fusion constructs protects against reoperation for pseudoarthrosis and/or instrumentation failure. However, the decision to include fusion supplements should be weighted between surgical determinants and clinical outcomes. PMID- 27396377 TI - Modified skin incision for avoiding the lesser occipital nerve and occipital artery during retrosigmoid craniotomy: potential applications for enhancing operative working distance and angles while minimizing the risk of postoperative neuralgias and intraoperative hemorrhage. AB - Chronic postoperative neuralgias and headache following retrosigmoid craniotomy can be uncomfortable for the patient. We aimed to better elucidate the regional nerve anatomy in an effort to minimize this postoperative complication. Ten adult cadaveric heads (20 sides) were dissected to observe the relationship between the lesser occipital nerve and a traditional linear versus modified U incision during retrosigmoid craniotomy. Additionally, the relationship between these incisions and the occipital artery were observed. The lesser occipital nerve was found to have two types of course. Type I nerves (60%) remained close to the posterior border of the sternocleidomastoid muscle and some crossed anteriorly over the sternocleidomastoid muscle near the mastoid process. Type II nerves (40%) left the posterior border of the sternocleidomastoid muscle and swung medially (up to 4.5cm posterior to the posterior border of the sternocleidomastoid muscle) as they ascended over the occiput. The lesser occipital nerve was near a midpoint of a line between the external occipital protuberance and mastoid process in all specimens with the type II nerve configuration. Based on our findings, the inverted U incision would be less likely to injure the type II nerves but would necessarily cross over type I nerves, especially more cranially on the nerve at the apex of the incision. As the more traditional linear incision would most likely transect the type I nerves and more so near their trunk, the U incision may be the overall better choice in avoiding neural and occipital artery injury during retrosigmoid approaches. PMID- 27396378 TI - A comparison of Staphylococcus aureus biofilm formation on cobalt-chrome and titanium-alloy spinal implants. AB - The use of cobalt chrome (CoCr) implants in spinal surgery has become increasingly popular. However, there have been no studies specifically comparing biofilm formation on CoCr with that of titanium-alloy spinal implants. The objective of this study was to compare the difference in propensity for biofilm formation between these two materials, as it specifically relates to spinal rods. Staphylococcus aureus subsp. Aureus (ATCC 6538) were incubated with two different types of spinal rods composed of either CoCr or titanium-alloy. The spinal rods were then subject to a trypsin wash to allow for isolation of the colonized organism and associated biofilms. The associated optical density values (OD) from the bacterial isolates were obtained and the bacterial solutions were plated on brain-heart infusion agar plates and the resultant colony-forming units (CFU) were counted. The OD values for the titanium-alloy rods were 1.105+/-0.096nm (mean+/-SD) and 1.040+/-0.026nm at 48hours and 96hours, respectively. In contrast, the OD values for the CoCr rods were 1.332+/-0.161nm and 1.115+/ 0.207nm at 48 and 96hours, respectively (p<0.05). The CFU values were 1481+/ 417/100mm(2) and 745+/-159/100mm(2) at 48 and 96hours, respectively for the titanium-alloy group. These values were significantly lower than the CFU values obtained from the CoCr group which were 2721+/-605/100mm(2) and 928+/-88/100mm(2) (p<0.001) at both 48 and 96hours respectively. Our findings, evaluating both the OD and CFU values, indicate that implants composed of CoCr had a higher proclivity towards biofilm formation compared to titanium-alloy implants. PMID- 27396379 TI - Will subspecialisation benefit the practice of Australasian emergency medicine? No. PMID- 27396380 TI - State dissociation moderates response to dialectical behavior therapy for posttraumatic stress disorder in women with and without borderline personality disorder. AB - BACKGROUND: Patients with posttraumatic stress disorder (PTSD) are prone to dissociation, which in theory should interfere with successful treatment. However, most empirical studies do not substantiate this assumption. OBJECTIVE: The primary objective was to test whether state dissociation predicts the success of an adaptation of dialectical behavior therapy designed for the treatment of patients with PTSD after childhood sexual abuse (CSA) (DBT-PTSD). We further explored whether the operationalization of dissociation as state versus trait dissociation made a difference with respect to prediction of improvement. METHODS: We present a hypothesis-driven post hoc analysis of a randomized controlled trial on the efficacy in patients with PTSD after CSA. Regression analyses relating pre-post improvements in the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS) to dissociation were applied to the women who participated in the active treatment arm (DBT-PTSD). Multivariate models accounting for major confounders were used to relate improvements in both the CAPS and the PDS to (1) state dissociation as assessed after each treatment session and (2) trait dissociation as assessed at baseline. RESULTS: State dissociation during psychotherapy sessions predicted improvement after DBT-PTSD: patients with low state dissociation during treatment had a higher chance to show substantial improvement. This relation consistently emerged across subgroups of PTSD patients with and without borderline personality disorder. The operationalization of dissociation as state versus trait dissociation made a difference as improvement was not significantly predicted from trait dissociation. CONCLUSIONS: Dissociation during treatment sessions may reduce success with trauma-focused therapies such as DBT-PTSD. Accordingly, clinical studies aimed at improving ways to address dissociation are needed. PMID- 27396382 TI - Ester of Quinoxaline-7-carboxylate 1,4-di-N-oxide as Apoptosis Inductors in K-562 Cell Line: An in vitro, QSAR and DFT Study. AB - BACKGROUND: Quinoxalines have shown a wide variety of biological activities including as antitumor agents. The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives on K562 cells, the establishment of the mechanism of induced cell death, and the construction of predictive QSAR models. MATERIAL AND METHODS: Sixteen esters of quinoxaline-7 carboxylate 1,4-di-N-oxide were evaluated for antitumor activity on K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models were created using genetic algorithms. RESULTS & CONCLUSIONS: Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 MUg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed. PMID- 27396381 TI - Late Stent Graft Infection after the Emergency Endovascular Repair of a Secondary Iliac Artery-Enteric Fistula Treated with Graft Removal and In Situ Aortic Reconstruction Using Femoral Veins. AB - An arterioenteric fistula is a devastating and life-threatening condition that requires urgent treatment. Less-invasive endovascular treatment has emerged as an alternative to conventional open repair, but postoperative graft infection remains a major concern. We herein report a case of late stent graft infection after emergency endovascular repair of a secondary iliac artery-enteric fistula. The patient was a 63-year-old male who presented with a fever, who had undergone successful endovascular stent grafting for a secondary common iliac artery enteric fistula 29 months prior. The diagnosis of a stent graft infection was confirmed via computed tomography. He underwent graft removal and in situ reconstruction with femoral vein grafts. At 6-month follow-up, the patient is in a good general condition without any symptoms. PMID- 27396383 TI - A transgenic-cloned pig model expressing non-fluorescent modified Plum. AB - Genetically modified pigs that express fluorescent proteins such as green and red fluorescent proteins have become indispensable biomedical research tools in recent years. Cell or tissue transplantation studies using fluorescent markers should be conducted, wherein the xeno-antigenicity of the fluorescent proteins does not affect engraftment or graft survival. Thus, we aimed to create a transgenic (Tg)-cloned pig that was immunologically tolerant to fluorescent protein antigens. In the present study, we generated a Tg-cloned pig harboring a derivative of Plum modified by a single amino acid substitution in the chromophore. The cells and tissues of this Tg-cloned pig expressing the modified Plum (mPlum) did not fluoresce. However, western blot and immunohistochemistry analyses clearly showed that the mPlum had the same antigenicity as Plum. Thus, we have obtained primary proof of principle for creating a cloned pig that is immunologically tolerant to fluorescent protein antigens. PMID- 27396384 TI - Expression and localization of members of the thrombospondin family during final follicle maturation and corpus luteum formation and function in the bovine ovary. AB - The aim of this study was to characterize the expression patterns and localization of the thrombospondin family members (THBS1, THBS2) and their receptors (CD36 and CD47) in bovine ovaries. First, the antral follicles were classified into 5 groups based on the follicle size and estradiol-17beta (E2) concentration in the follicular fluid (< 0.5, 0.5-5, 5-40, 40-180 and >180 E2 ng/ml). Second, the corpus luteum (CL) was assigned to the following stages: days 1-2, 3-4, 5-7, 8-12, 13-16 and >18 of the estrous cycle and of pregnancy (month 1 2, 3-4, 6-7 and > 8). Third, the corpora lutea were collected by transvaginal ovariectomy before and 0.5, 2, 4, 12, 24, 48 and 64 h after inducing luteolysis by injecting a prostaglandin F2alpha analog. The mRNA expression of examined factors was measured by RT-qPCR, steroid hormone concentration by EIA, and localization by immunohistochemistry. The mRNA expression of THBS1, THBS2, CD36, and CD47 in the granulosa cells and theca interna was high in the small follicles and reduced in the preovulatory follicles. The mRNA expression of THBS1, THBS2, and CD47 in the CL during the estrous cycle was high, but decreased significantly during pregnancy. After induced luteolysis, thrombospondins increased significantly to reach the maximum level at 12 h for THBS1, 24 h for THBS2, and 48 h for CD36. The temporal expression and localization pattern of the thrombospondins and their specific receptors in the antral follicles and corpora lutea during the different physiological phases of the estrous cycle and induced luteolysis appear to be compatible with their inhibitory role in the control of ovarian angiogenesis. PMID- 27396385 TI - Superovulation with a single administration of FSH in aluminum hydroxide gel: a novel superovulation method for cattle. AB - Superovulation (SOV) is a necessary technique to produce large numbers of embryos for embryo transfer. In the conventional methods, follicular stimulating hormone (FSH) is administered to donor cattle twice daily for 3 to 4 days. As this method is labor intensive and stresses cattle, improving this method has been desired. We previously developed a novel and simple SOV method, in which the intramuscular injection of a single dose of FSH in aluminum hydroxide gel (AH-gel) induced the growth of multiple follicles, ovulation and the production of multiple embryos. Here we show that AH-gel can efficiently adsorb FSH and release it effectively in the presence of BSA, a major interstitial protein. When a single intramuscular administration of the FSH and AH-gel mixture was performed to cattle, multiple follicular growth, ovulation and embryo production were induced. However, the treatments caused indurations at the administration sites in the muscle. To reduce the muscle damage, we investigated alternative administration routes and different amounts of aluminum in the gel. By administering the FSH in AH-gel subcutaneously rather than intramuscularly, the amount of aluminum in the gel could be reduced, thus reducing the size of the induration. Moreover, repeated administrations of FSH with AH-gel did not affect the superovulatory response. These results indicate that a single administration of FSH with AH-gel is an effective, novel and practical method for SOV treatment. PMID- 27396387 TI - Pharmacokinetics of Gefitinib: Roles of Drug Metabolizing Enzymes and Transporters. AB - Gefitinib (Iressa, AstraZeneca) has been widely used for the treatment of locally advanced or metastatic non-small cell lung cancer. A number of studies have been reported on its pharmacokinetics profiles, especially on the metabolism. In this review, we have comprehensively summarized the pharmacokinetic characteristics of gefitinib: absorption, distribution, metabolism and excretion (ADME). Overall, gefitinib reached the maximum plasma level relatively fast and distributed extensively. It underwent extensive biotransformation and predominantly excreted in feces, with less than 7% in the urine. CYP450 enzymes played critical roles in the process of gefitinib metabolism. The major enzyme involved in the metabolism was CYP3A4, with other CYP450 enzymes playing a secondary role. A high clearance of gefitinib might result in drug resistance by lowering drug concentration. The enhanced efflux and decreased uptake by transporters were important resistance mechanisms. The transporters involved in pharmacokinetics of gefitinib consist of the ATP-binding cassette and the solute carrier superfamily. Understanding the pharmacokinetics property of gefitinib may provide valuable and new information for dealing with drug resistance and making personalized therapy regarding their interindividual variability. PMID- 27396386 TI - Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study. AB - BACKGROUND: Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression. METHOD: We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis. RESULTS: ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years. CONCLUSIONS: Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis. PMID- 27396389 TI - Near-Infrared Spectroscopy: More Accurate Than Heart Rate for Monitoring Intensity in Running in Hilly Terrain. AB - PURPOSE: To investigate the cardiorespiratory and metabolic response of trail running and evaluate whether heart rate (HR) adequately reflects the exercise intensity or if the tissue-saturation index (TSI) could provide a more accurate measure during running in hilly terrain. METHODS: Seventeen competitive runners (4 women, VO2max, 55 +/- 6 mL . kg-1 . min-1; 13 men, VO2max, 68 +/- 6 mL . kg-1 . min-1) performed a time trial on an off-road trail course. The course was made up of 2 laps covering a total distance of 7 km and included 6 steep uphill and downhill sections with an elevation gain of 486 m. All runners were equipped with a portable breath-by-breath gas analyzer, HR belt, global positioning system receiver, and near-infrared spectroscopy (NIRS) device to measure the TSI. RESULTS: During the trail run, the exercise intensity in the uphill and downhill sections was 94% +/- 2% and 91% +/- 3% of maximal heart rate, respectively, and 84% +/- 8% and 68% +/- 7% of VO2max, respectively. The oxygen uptake (VO2) increased in the uphill sections and decreased in the downhill sections (P < .01). Although HR was unaffected by the altering slope conditions, the TSI was inversely correlated to the changes in VO2 (r = -.70, P < .05). CONCLUSIONS: HR was unaffected by the continuously changing exercise intensity; however, TSI reflected the alternations in VO2. Recently used exclusively for scientific purposes, this NIRS-based variable may offer a more accurate alternative than HR to monitor running intensity in the future, especially for training and competition in hilly terrain. PMID- 27396388 TI - Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells. AB - The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG proBs open interesting perspectives for cell therapy of autoimmune diseases. PMID- 27396390 TI - A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors. AB - Exosomes and microvesicles, which are released by most of the cells, play important roles in intracellular correspondence by transferring DNA, messenger RNA, micro RNA, and other types of RNA and proteins. Exosomes and microvesicles may contribute to the distribution of cancers and diseases through delivering the pathogenic agents to the non-infected cells; in cancers, they can modify the cells in the tumor niche and lead them to transformation. In addition, these vesicles can affect stem cell activity and their physiological properties. On the other hand, exosomes and microvesicles can be applied in the therapeutic strategies as they are small, non-viral, flexible and able to cross biological barriers. In this review, we focused on some details about the exosomes and microvesicles both functionally and structurally. PMID- 27396391 TI - A highly sensitive, highly transparent, gel-gated MoS2 phototransistor on biodegradable nanopaper. AB - Transition metal dichalcogenides hold great promise for a variety of novel electrical, optical and mechanical devices and applications. Among them, molybdenum disulphide (MoS2) is gaining increasing attention as gate dielectrics and semiconductive channels for high-performance field effect transistors. Here we report on the first MoS2 phototransistor built on a flexible, transparent and biodegradable substrate with an electrolyte gate dielectric. We have carried out systematic studies on its electrical and optoelectronic properties. The MoS2 phototransistor exhibited an excellent photoresponsivity of ~1.5 kA W(-1), about two times higher compared to typical back-gated devices reported in previous studies. The device is highly transparent at the same time with an average optical transmittance of 82%. Successful fabrication of phototransistors on flexible cellulose nanopaper with excellent performance and transparency suggests that it is feasible to achieve an ecofriendly and biodegradable phototransistor with great photoresponsivity, broad spectral range and durable flexibility. PMID- 27396392 TI - An acid-cleavable phthalocyanine tetramer as an activatable photosensitiser for photodynamic therapy. AB - An acetal-linked self-quenched zinc(ii) phthalocyanine tetramer has been prepared. In an acidic environment in phosphate buffered saline or inside tumour cells, the phthalocyanine units of the tetramer are separated thereby restoring the fluorescence emission and singlet oxygen production. This response enables this compound to serve as a promising activatable photosensitiser for photodynamic therapy. PMID- 27396393 TI - Regioselective synthesis of 3-anthracenyloxindoles and 3-carbazolyloxindoles by indium(iii)-catalyzed direct arylation and their fluorescent chemosensor properties. AB - An efficient, facile and regioselective strategy was developed for the construction of diverse 3-anthracenyloxindoles and 3-carbazolyloxindoles via In(OTf)3-catalyzed direct arylation reaction of 3-diazooxindoles with anthracenes or carbazoles. This novel methodology involved new C-C bond formation between oxindoles and anthracenes or carbazoles. The fluorescence response of the synthesized compounds to heavy metal ions was also investigated. PMID- 27396394 TI - A Systematic Review of the Uterine Relaxant Effect of Herbal Sources. AB - BACKGROUND: Preterm birth is a worldwide tragedy with a high incidence. Several medications are used to inhibit acute preterm labor, but tocolysis by these medicines do not extend pregnancy beyond 1-2 days. OBJECTIVES: The purpose of this study was to discover new medications from plant extracts or their active compounds which inhibit the uterine contractions in order to treat preterm labor. DATA SOURCES: PubMed, Google Scholar, Scopus and IranMedex databases were searched up to 1st February 2012 with the most relevant keywords. STUDY SELECTION: All studies in which plant extracts or their active compounds inhibited the uterine contractions both in vivo and in vitro were included. THE RESULTS: Of initial search, 259 records were reviewed and finally 72 were included among which only 31 studies isolated an active compound from the plants extract belonging mostly to classes of flavonoids and terpenes classes. Flavonoids have been known as a phosphodiesterase (PDE) and a protein kinase C (PKC) inhibitor. It seems that the uterolytic activity of reviewed flavonoids such as naringenin, kaempferol and quercetin, especially in a calcium free solution, was via these inhibitory pathways. CONCLUSION: Laboring uterus response to dissimilar tocolytics differs from that of non-laboring uterus. In order to find a treatment for preterm labor, future studies should focus on the laboring uterus and also determine the structure activity relationship of the different tocolytics. This systematic review was registered to the PROSPERO with code number CRD42015027551. PMID- 27396395 TI - Upconversion luminescence of lanthanide-doped mixed CaMoO4-CaWO4 micro-/nano materials. AB - Uniform mixed CaMoO4-CaWO4 micro-/nano-materials have been successfully synthesised by a facile hydrothermal method. The morphology of these upconversion materials could be changed to different shapes and the size could also be decreased from the micro- to nano-scale by varying the type of surfactant used. It was observed that before heat treatment, the materials show relatively weak green light emission under excitation at 975 nm, whereas after heat treatment, the intensity of the upconversion luminescence increases dramatically while the intensity of the red component decreases relatively. By adjusting the molybdate/tungstate ratio, it was found that the samples with a higher molybdate content have stronger luminescence properties. XRD measurements have been done to investigate the structure of the mixed CaMoO4-CaWO4 upconversion materials. The effect of heat treatment at different temperatures on the emission spectra and XRD patterns has also been studied. TG-DTA was used to further confirm the most suitable temperature for heat treatment. The luminescence lifetimes and CIE coordinates for these samples were also determined. Additionally it was found that Gd(3+) co-doping could further increase the upconversion luminescence from these mixed CaMoO4-CaWO4 materials. Finally, monitoring the upconversion luminescence intensity as a function of laser pump power confirmed the upconversion process to be a two-photon absorption mechanism. PMID- 27396396 TI - Perioperative Management Center (PERIO) for Neurosurgical Patients. AB - Perioperative management is critical for positive neurosurgical outcomes. In order to maintain safe and authentic perioperative management, a perioperative management center (PERIO) was introduced to patients of our Neurosurgery Department beginning in June 2014. PERIO involves a multidisciplinary team consisting of anesthesiologists, dentists/dental hygienists/technicians, nurses, physical therapists, pharmacists, and nutritionists. After neurosurgeons decide on the course of surgery, a preoperative evaluation consisting of blood sampling, electrocardiogram, chest X-ray, and lung function test was performed. The patients then visited the PERIO clinic 7-14 days before surgery. One or two days before surgery, the patients without particular issues enter the hospital and receive a mouth cleaning one day before surgery. After surgery, postoperative support involving eating/swallowing evaluation, rehabilitation, and pain control is provided. The differences in duration from admission to surgery, cancellation of surgery, and postoperative complications between PERIO and non-PERIO groups were examined. Eighty-five patients were enrolled in the PERIO group and 131 patients in the non-PERIO group. The duration from admission to surgery was significantly decreased in the PERIO group (3.6 +/- 0.3 days), compared to that in the non-PERIO group (4.7 +/- 0.2 days). There was one cancelled surgery in the PERIO group and six in the non-PERIO group. Postoperative complications and the overall hospital stay did not differ between the two groups. The PERIO system decreased the duration from admission to surgery, and it is useful in providing high-quality medical service, although the system should be improved so as not to increase the burden on medical staff. PMID- 27396397 TI - Detection of pathogenic Yersinia enterocolitica in pet Djungarian hamsters in Japan. AB - The prevalence of Yersinia enterocolitica (Y. enterocolitica) and Yersinia pseudotuberculosis was examined in 151 pet animals including 108 rodents, 39 rabbits and four sugar gliders from 13 pet stores in the Yamaguchi Prefecture, Japan. Y. enterocolitica serogroup O:3 biotype 3 negative for the Voges-Proskauer reaction (O:3/3 variant VP-) was isolated from five Djungarian hamsters (Phodopus sungorus) raised at the same pet store. These pathogenic Y. enterocolitica isolates carried the virulence genes, yadA, ail and virF, and were shown to be clonal by pulsed-field gel electrophoresis with NotI digestion. This is a first report of pathogenic Y. enterocolitica O:3/3 variant VP- in pet Djungarian hamsters in Japan. PMID- 27396398 TI - Theileria annulata seroprevalence among different cattle breeds in Rajshahi Division, Bangladesh. AB - An epidemiological survey of Theileria annulata infection was undertaken in a cattle population in Rajshahi Division, Bangladesh. The local cattle breeds from the area (North Bengal Gray and Deshi) and crosses between the local breeds and Holstein cattle were predominantly screened. In total, 192 cattle serum samples were collected in two areas of Rajshahi Division, the Rajshahi District (n=147) and Natore District (n=45). The samples were screened with an enzyme-linked immunosorbent assay using T. annulata surface protein (TaSP) as the antigen. The seroprevalence was 80.0% (36/45) in Natore and 20.4% (30/147) in Rajshahi. A logistic regression analysis showed that the sampling location was significantly associated with seropositivity, whereas age, sex and breed were not. Although the logistic regression analysis did not show a linear dependence on age, we considered age-specific seroprevalence separately in the two districts. Seroprevalence did not differ significantly among age categories in the Natore District. In contrast, all the cattle <1 year old in the Rajshahi District were seronegative (11/11). Seroprevalence in the 1- and 2-year-old cattle was significantly lower in the Rajshahi District than in the Natore District. In the older age categories (3, 4 and >5 years), seroprevalence did not differ significantly between the Natore and Rajshahi Districts. These results suggest that the cattle in the Rajshahi District were sporadically exposed to T. annulata, whereas most cattle in the Natore District became infected during an early phase of life. PMID- 27396399 TI - Delta- and gamma-tocotrienol isomers are potent in inhibiting inflammation and endothelial activation in stimulated human endothelial cells. AB - BACKGROUND: Tocotrienols (TCTs) are more potent antioxidants than alpha tocopherol (TOC). However, the effectiveness and mechanism of the action of TCT isomers as anti-atherosclerotic agents in stimulated human endothelial cells under inflammatory conditions are not well established. AIMS: 1) To compare the effects of different TCT isomers on inflammation, endothelial activation, and endothelial nitric oxide synthase (eNOS). 2) To identify the two most potent TCT isomers in stimulated human endothelial cells. 3) To investigate the effects of TCT isomers on NFkappaB activation, and protein and gene expression levels in stimulated human endothelial cells. METHODS: Human umbilical vein endothelial cells were incubated with various concentrations of TCT isomers or alpha-TOC (0.3 10 uM), together with lipopolysaccharides for 16 h. Supernatant cells were collected and measured for protein and gene expression of cytokines (interleukin 6, or IL-6; tumor necrosis factor-alpha, or TNF-alpha), adhesion molecules (intercellular cell adhesion molecule-1, or ICAM-1; vascular cell adhesion molecule-1, or VCAM-1; and e-selectin), eNOS, and NFkappaB. RESULTS: delta-TCT is the most potent TCT isomer in the inhibition of IL-6, ICAM-1, VCAM-1, and NFkappaB, and it is the second potent in inhibiting e-selectin and eNOS. gamma TCT isomer is the most potent isomer in inhibiting e-selectin and eNOS, and it is the second most potent in inhibiting is IL-6, VCAM-1, and NFkappaB. For ICAM-1 protein expression, the most potent is delta-TCT followed by alpha-TCT. alpha- and beta-TCT inhibit IL-6 at the highest concentration (10 uM) but enhance IL-6 at lower concentrations. gamma-TCT markedly increases eNOS expression by 8-11 fold at higher concentrations (5-10 uM) but exhibits neutral effects at lower concentrations. CONCLUSION: delta- and gamma-TCT are the two most potent TCT isomers in terms of the inhibition of inflammation and endothelial activation whilst enhancing eNOS, possibly mediated via the NFkappaB pathway. Hence, there is a great potential for TCT isomers as anti-atherosclerotic agents. PMID- 27396400 TI - Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique. AB - BACKGROUND: Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. OBJECTIVE: The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). METHODS: Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. RESULTS: Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. CONCLUSION: Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research. PMID- 27396401 TI - Memory Enhancing Effect of Black Pepper in the AlCl3 Induced Neurotoxicity Mouse Model is Mediated Through Its Active Component Chavicine. AB - Black pepper (Piper nigrum Linn.) has vital pharmacological properties with profound effects on central nervous system. Neurotoxic agents like Aluminum Chloride (AlCl3) cause the oxidative stress and result in improper processing of amyloid proteins leading to accumulation of amyloid beta plaques. AIM: The study aimed to explore the neuroprotective potential of black pepper (BP) extract (12.5mg/kg/day) on memory enhancement and its effect on expression of amyloid precursor protein (APP) isoforms (APP770 and APP695) in AlCl3 induced neurotoxicity (250mg/kg) mouse model. The study included the isolation and identification of pure compound from BP (chavicine) which was found pharmacologically active. METHODS: Morris water maze test, elevated plus maze, fear conditioning, context and cue dependent test and social preference tests were performed to investigate the learning and memory. Gene expression (APP isoforms) and in-vitro and ex-vivo DPPH free radical scavenging activity were performed to evaluate the role of BP. RESULTS: BP significantly improved memory in AlCl3 induced neurotoxicity mouse model along with effectively decreasing the expression of APP770 (amyloidogenic) isoform and improved level of APP695 (non amyloidogenic) in hippocampus, amygdala and cortex. Fear extinction learning was considerably improved in BP treated group (7.83+/-2.03) than AlCl3 induced neurotoxicity group (39.75+/-4.25). In the hippocampus, BP significantly reduced the expression of APP770 (0.37+/-0.05) as compared to AlCl3 induced neurotoxicity group (0.72+/-0.06), and effectively increased (34.80+/-1.39) the percentage inhibition of DPPH free radicals as compared to AlCl3 induced neurotoxicity group (14+/-2.68). CONCLUSION: The study revealed that BP improves memory and chavicine is a lead compound producing pharmacological effects of BP. PMID- 27396402 TI - Plasma Rich in Growth Factors Inhibits Ultraviolet B Induced Photoageing of the Skin in Human Dermal Fibroblast Culture. AB - BACKGROUND: Ultraviolet irradiation is able to deeply penetrate into the dermis and alter fibroblast structure and function, leading to a degradation of the dermal extracellular matrix. OBJECTIVES: The regenerative effect of plasma rich in growth factors (PRGF) on skin ageing was investigated using UVB photo-stressed human dermal fibroblasts as an in vitro culture model. METHOD: PRGF was assessed over the main indicative features of ultraviolet B irradiation, including ROS formation, cell viability and death detection, apoptosis/ necrosis analysis and biosynthetic activity measurement. Four different UV irradiation protocols were tested in order to analyze the beneficial effects of PRGF. RESULTS: Ultraviolet irradiation exhibited a dose dependent cytotoxicity and dose of 400mJ/cm2 was selected for subsequent experiments. PRGF increased the cell viability and decreased the cell death comparing to the non-treated group. The apoptosis and necrosis were significantly lower in PRGF treated fibroblasts. ROS production after UV irradiation was significantly reduced in the presence of PRGF. Procollagen type I, hyaluronic acid and TIMP-1 levels were higher in the when treated with PRGF. CONCLUSION: This preliminary in vitro study suggests that PRGF is able to prevent UVB derived photooxidative stress and to diminish the cell damage caused by ultraviolet irradiation. PMID- 27396403 TI - Reverse Pharmacognosy and Reverse Pharmacology; Two Closely Related Approaches for Drug Discovery Development. AB - Pharmacognosy is a science, which study natural products as a source of new drug leads and effective drug development. Rational and economic search for novel lead structures could maximize the speed of drug discovery by using powerful high technology methods. Reverse pharmacognosy, a complementary to pharmacognosy, couples the high throughput screening (HTS), virtual screening and databases along with the knowledge of traditional medicines. These strategies lead to identification of numerous in vitro active and selective hits enhancing the speed of drug discovery from natural sources. Besides, reverse pharmacology is a target base drug discovery approach; in the first step, a hypothesis is made that the alteration of specific protein activity will produce beneficial curative effects. Both, reverse pharmacognosy and reverse pharmacology take advantages of high technology methods to accomplish their particular purposes. Moreover, reverse pharmacognosy effectively utilize traditional medicines and natural products as promising sources to provide new drug leads as well as promote the rational use of them by using valuable information like protein structure databases and chemical libraries which prepare pharmacological profile of traditional medicine, plant extract or natural compounds. PMID- 27396404 TI - Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects. AB - Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g( 1). The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80 SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80 SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the theranostic treatment of CNS diseases. PMID- 27396405 TI - Development of a comprehensive analytical method for furanocoumarins in grapefruit and their metabolites in plasma and urine using UPLC-MS/MS: a preliminary study. AB - To develop a comprehensive analytical method for photoactive furanocoumarins, grapefruit (whole, flesh, peel and juice) was extracted using QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. Seven furanocoumarins: bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6',7'-DHB), epoxybergamottin and bergamottin were determined in grapefruit using UPLC-MS/MS. The concentrations of furanocoumarins in the plasma and urine of six healthy young adults before and after ingestion of grapefruit or grapefruit juice were also determined. Recovery rates of furanocoumarins by QuEChERS method from matrix spike sample and laboratory calibrate sample were 125.7 +/- 25.4% and 105.7 +/- 6.3%, respectively. Bergamottin and 6',7'-DHB were predominant compounds in grapefruit flesh, juice and plasma, while bergaptol and 6',7'-DHB were major compounds detected in the urine. The results demonstrated that bergamottin and 6',7'-DHB were metabolized to bergaptol. Overall, the analytical methods developed in the present study can be applied to the analysis of various furanocoumarins in plant sources and biological samples. PMID- 27396406 TI - Elevations in the Levels of NF-kappaB and Inflammatory Chemotactic Factors in the Brains with Alzheimer's Disease - One Mechanism May Involve alpha3 Nicotinic Acetylcholine Receptor. AB - The purpose of this study was to investigate the alterations in the levels of nuclear factor kappaBp65 (NF-kappaBp65), monocyte chemoattractant protein 1 (MCP 1/CCL-2) and macrophage inflammatory protein 1alpha (MIP-1alpha/CCL-3) in relationship to the expression of alpha3 nicotinic acetylcholine receptor (nAChR) during the pathogenesis of Alzheimer's disease (AD). The post-mortem human brains of AD and age-matched control individuals, SH-SY5Y and U87MG cell lines exposed to beta-amyloid peptide (Abeta), as well as the SH-SY5Y cells in which alpha3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-kappaBp65, MCP-1, MIP-1alpha and alpha3 nAChR. The immunohistochemistry results showed the increased immunoreactivities of NF kappaBp65, MCP-1 and MIP-1alpha in neurons in hippocampal and temporal and frontal regions of AD brains. Levels of NF-kappaBp65, MCP-1 and MIP-1alpha at both protein and mRNA levels were all significantly up-regulated in SH-SY5Y and U87MG cells exposed to Abeta1-42, while expression of alpha3 nAChRs in Abeta1-42 exposed SH-SY5Y cells was attenuated. Interestingly, in the SH-SY5Y cells subjected to alpha3 nAChR mRNA silencing, expression of NF-kappaBp65, MCP-1 and MIP-1alpha was elevated. The elevated expressions of NF- kappaB and chemokines may be involved by decreased expression of alpha3 nAChRs during the pathogenesis of AD. PMID- 27396407 TI - Genetically-mediated Grey and White Matter Alteration in Normal Elderly Individuals with the CLU-C Allele Gene. AB - BACKGROUND: Several genome-wide association studies have found that the rs11136000 polymorphism of the C allele (CLU-C) is associated with the risk for developing late-onset Alzheimer's disease (LOAD). However, the effects of the CLU C/C genotype on brain structure, including gray and white matter, are not adequately understood. OBJECTIVES: We aimed to clarify the gray matter and white matter integrity changes in non-demented ageing individuals with the AD risk gene of the rs11136000 polymorphism of the C allele (CLU-C) and the correlation with cognitive performance. METHODS: Voxel-based analysis was used to compare the differences in high-resolution structural T1 and diffusion tensor imaging data between 31 CLU-C/C and 15 non-CLU-C/C carriers in nondemented older adults. RESULTS: Compared to non-CLU-C/C carriers, CLU-C homozygotes showed a reduced gray matter concentration (GMC) in the left parahippocampal gyrus, right middle frontal and temporal middle gyri, increased GMC in the left middle frontal and right fusiform gyri and increased gray matter volume (GMV) in the left middle frontal gyrus (P < 0.001). Decreased fractional anisotropy (FA) in the sub-gyral white matter of the left external capsule and left anterior cingulate and increased FA in the sub-gyral white matter of the left temporal lobe were also found in CLU-C/C genotype carriers. Moreover, the FA value in the left external capsule correlated with several cognitive measures. CONCLUSION: Our findings provide further evidence for the CLU risk variant as a candidate gene for AD and may serve as a pre-clinical neuroimaging phenotype of late-onset AD. PMID- 27396409 TI - Isoprene polymerization mediated by vanadium-[ONNO] complexes. AB - A series of vanadium complexes bearing dianionic tetradentate amine-bisphenolate [ONNO] ligands, V([double bond, length as m-dash]O)X[ONNO(Me)] (X = Cl (1); O(i)Pr (2)), VCl2[ONNO(Me)] (3) and V(O(i)Pr)2[ONNO(R)] (R = Me (4), (t)Bu (5), Cl (6)), displaying various electronic and steric properties have been prepared. The molecular structures of two of these complexes, namely V[ONNO(R)](O(i)Pr)2 with R = (t)Bu (5) or Cl (6), are reported. Activated with dialkylmagnesium, all complexes lead to modest isoprene homo-polymerization activities at 50 degrees C. Quantitative polymerizations were observed using 4 and 6 as pre-catalysts combined with Al(i)Bu3. The resulting polyisoprene microstructure was composed of ca. 70% 3,4 enchainments, the remaining 30% 1,4 enchainments being a mixture of cis and trans stereoisomers. 6 leads to a more active catalyst than 4. beta Hydride abstraction occurs during the reaction. PMID- 27396408 TI - Hypoglycemic activity of the Baker's yeast beta-glucan in obese/type 2 diabetic mice and the underlying mechanism. AB - SCOPE: beta-Glucans have been shown to reduce the risk of obesity and diabetes. However, they often contain diverse polysaccharides and other ingredients, leading to elusive experimental data and mechanisms. In this study, a pure beta glucan was obtained from the crude Baker's yeast polysaccharides for investigating its effect on the metabolic disorders in high-fat diet induced obese (DIO)/type 2 diabetic (T2D) mice and the underlying mechanism. METHODS AND RESULTS: The Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy data indicated that the pure beta-glucan (BYGlc) was a linear beta-(1->3)-glucan. It was first found that the oral administration of BYGlc into T2D and DIO mice significantly downregulated the blood glucose through suppressing sodium-glucose transporter-1 expression in intestinal mucosa. Meanwhile, BYGlc promoted glycogen synthesis and inhibited fat accumulation in liver, and depressed macrophage infiltration and pro-inflammatory cytokines production measured by histochemistry/immunohistochemistry and ELISA. Additionally, BYGlc remarkably decreased Firmicutes population and increased the proportion of Akkermansia by 16S rDNA analysis. CONCLUSION: BYGlc showed hypoglycemic activity accompanied by promotion of metabolism and inhibition of inflammation in T2D/DIO mice model. The hypoglycemic mechanisms were first declared to be through suppressing sodium-glucose transporter-1 expression and possibly associated with the altered gut microbiota. PMID- 27396410 TI - Structure-Activity Relationship Study Reveals Benzazepine Derivatives of Luteolin as New Aldose Reductase Inhibitors for Diabetic Cataract. AB - Hyperglycaemia in diabetic patients causes diverse range of complications and the earliest among them is diabetic cataract. The role of aldose reductase, the key enzyme in polyol pathway, is well known in the genesis of cataract in chronic diabetic patients. Controlling of sorbitol flux into lens epithelial cells through aldose reductase inhibitors is an important treatment strategy. Due to the side effects of many drugs so far developed, the development of aldose reductase inhibitors from natural sources has gained considerable attention. This study was undertaken to identify suitable drugs for diabetic cataract using molecular modeling and simulation methods. A series of 18 luteolin derivatives having in vitro inhibitory potential against aldose reductase was used to develop a common pharmacophore hypothesis AHRRR and atom-based 3D-QSAR model. The model was used for virtual screening of ZINC database and the resultant hits were docked against aldose reductase. The two drug candidates which belonged to benzazepine class of drugs scored high in the molecular docking. They were further examined for their activity and pharmacokinetic behaviour. Their druglikeness behaviour was found suitable to be used as drugs as per Lipinski's rule of five criteria. Human intestinal absorption (HIA), skin permeability (SP), blood brain barrier (BBB) penetration and plasma protein binding (PPB) was found to be in the acceptable range. Based on the results, these drugs could be considered as potential candidates in further drug development against diabetic cataract. PMID- 27396411 TI - Piezoelectric enhancement under negative pressure. AB - Enhancement of ferroelectric properties, both spontaneous polarization and Curie temperature under negative pressure had been predicted in the past from first principles and recently confirmed experimentally. In contrast, piezoelectric properties are expected to increase by positive pressure, through polarization rotation. Here we investigate the piezoelectric response of the classical PbTiO3, Pb(Zr,Ti)O3 and BaTiO3 perovskite ferroelectrics under negative pressure from first principles and find significant enhancement. Piezoelectric response is then tested experimentally on free-standing PbTiO3 and Pb(Zr,Ti)O3 nanowires under self-sustained negative pressure, confirming the theoretical prediction. Numerical simulations verify that negative pressure in nanowires is the origin of the enhanced electromechanical properties. The results may be useful in the development of highly performing piezoelectrics, including lead-free ones. PMID- 27396412 TI - Curing and viscoelasticity of vitrimers. AB - We present an experimental investigation of the curing kinetics and viscoelasticity for a number of "vitrimers" recently developed by Leibler and coworkers.1-3 Vitrimers are covalently crosslinked networks that can relax stress at elevated temperatures due to thermoreversible bond-exchange reactions. The chosen formulations are composed of diglycidyl ether of bisphenol A, commercial fatty acid mixtures and an appropriate catalyst. The effects of the catalyst and functionality of the curing agents on the kinetics of the curing reactions were systematically investigated using rheometry. The curing kinetics followed the Arrhenius law and the catalyst drastically accelerated the reactions. Time temperature superposition was used to construct master curves of the small-strain amplitude oscillatory shear moduli over wide ranges of frequencies for the cured networks. Terminal relaxation was not reached in oscillatory experiments for temperatures up to 130 degrees C and creep and stress relaxation experiments were used to probe the long-time relaxation. The shift factors displayed a Williams-Landel-Ferry dependence on temperature which could be divided into two regions, one above 70 degrees C, where the dynamics appeared to be controlled by the catalyst, and one below, controlled by the monomeric friction and the free volume of the network. The moduli of the vitrimers obeyed the classical rubber theory well, indicating that the curing reactions proceeded to completion. Furthermore, we systematically and reproducibly observed a double relaxation behavior for the vitrimers, i.e. next to the rubbery plateau at high frequencies, the storage modulus displayed a secondary plateau at lower frequencies before reaching terminal relaxation at even lower frequencies. Interestingly, 70 degrees C was found to be the transition point in agreement with the shift factors. To the best of our knowledge, the double relaxation behavior has not been previously reported in experimental works and recent theories do not incorporate an explanation for this behavior. Consequently, future investigations concerning the viscoelasticity of other "vitrimer-chemistries" are important to assess if the double relaxation is a universal fingerprint for vitrimers or if it is specific to the here-investigated formulations based on commercial fatty acid mixtures. PMID- 27396413 TI - Direct Formation of Oxocarbenium Ions under Weakly Acidic Conditions: Catalytic Enantioselective Oxa-Pictet-Spengler Reactions. AB - Two catalysts, an amine HCl salt and a bisthiourea, work in concert to enable the generation of oxocarbenium ions under mild conditions. The amine catalyst generates an iminium ion of sufficient electrophilicity to enable 1,2-attack by an alcohol. Catalyst turnover is achieved by amine elimination with concomitant formation of an oxocarbenium intermediate. The bisthiourea catalyst accelerates all of the steps of the reaction and controls the stereoselectivity via anion binding/ion pair formation. This new concept was applied to direct catalytic enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes. PMID- 27396415 TI - Frontiers in Nanoscale Electrochemical Imaging: Faster, Multifunctional, and Ultrasensitive. AB - A wide range of interfacial physicochemical processes, from electrochemistry to the functioning of living cells, involve spatially localized chemical fluxes that are associated with specific features of the interface. Scanning electrochemical probe microscopes (SEPMs) represent a powerful means of visualizing interfacial fluxes, and this Feature Article highlights recent developments that have radically advanced the speed, spatial resolution, functionality, and sensitivity of SEPMs. A major trend has been a coming together of SEPMs that developed independently and the use of established SEPMs in completely new ways, greatly expanding their scope and impact. The focus is on nanopipette-based SEPMs, including scanning ion conductance microscopy (SICM), scanning electrochemical cell microscopy (SECCM), and hybrid techniques thereof, particularly with scanning electrochemical microscopy (SECM). Nanopipette-based probes are made easily, quickly, and cheaply with tunable characteristics. They are reproducible and can be fully characterized. Their response can be modeled in considerable detail so that quantitative maps of chemical fluxes and other properties (e.g., local charge) can be obtained and analyzed. This article provides an overview of the use of these probes for high-speed imaging, to create movies of electrochemical processes in action, to carry out multifunctional mapping such as simultaneous topography-charge and topography-activity, and to create nanoscale electrochemical cells for the detection, trapping, and analysis of single entities, particularly individual molecules and nanoparticles (NPs). These studies provide a platform for the further application and diversification of SEPMs across a wide range of interfacial science. PMID- 27396414 TI - Self-awareness of cognitive efficiency: Differences between healthy elderly and patients with mild cognitive impairment (MCI). AB - INTRODUCTION: Self-estimation of performance implies the ability to understand one's own performance with relatively objective terms. Up to date, few studies have addressed this topic in mild cognitive impairment (MCI) patients. The aim of the present study was to compare objective measures of performance with subjective perception of specific performance on cognitive tests and investigate differences in assessment between MCI patients and healthy elderly. METHOD: Thirty-five participants diagnosed with MCI (women = 16, men = 19, mean age = 65.09 years +/-SD = 7.81, mean education = 12.83 years +/-SD = 4.32) and 35 control subjects similar in terms of age and education (women = 20, men = 15, mean age = 62.46 years +/- SD = 9.35, mean education = 14.26 +/- SD = 2.84) were examined with an extended battery of neuropsychological tests. After every test they were asked to self-evaluate their performance by comparing it to what they considered as average for people of their age and educational level. This self evaluation was reported on a scale ranging from -100 to +100. RESULTS: Significant differences were found in the self-assessment patterns of the two groups in memory measures of verbal and visual delayed recall, visuospatial perception, and tests of attention. MCI patients overestimated their performance on every cognitive domain while control participants underestimated their performance on measures of verbal memory. CONCLUSIONS: The present results indicate that accuracy of self-report is not uniform across groups and functional areas. The discrepancies in the MCI patients indicate unawareness of their memory deficits, which is contradictory to subjective memory complaints as being an important component for clinical diagnosis. PMID- 27396416 TI - Resting extracellular signal-regulated protein kinase 1/2 expression following a continuum of chronic resistance exercise training paradigms. AB - Extracellular signal-regulated protein kinase 1/2 (ERK1/2) moderates skeletal muscle growth; however, chronic responses of this protein to unique resistance exercise (RE) paradigms are yet to be explored. The purpose of this investigation was to describe the long-term response of ERK1/2 following circuit weight training (CWT), recreationally weight training (WT), powerlifting (PL) and weightlifting (WL). Independent t-tests were used to determine differences in trained groups compared to sedentary controls. Total ERK1/2 content was lower in PL and WL compared to their controls (p <= 0.05). Specific trained groups displayed large (WL: pERK/total-ERK; d = 1.25) and moderate (CWT: total ERK1/2; d = 0.54) effect sizes for altered kinase expression compared to controls. The results indicate ERK1/2 expression is down-regulated after chronic RE in well trained weightlifters and powerlifters. Lower expression of this protein may be a method in which anabolism is tightly regulated after many years of high-intensity RE. PMID- 27396418 TI - Welcome Address. PMID- 27396417 TI - The 9th Belgian Surgical Week is organised together with. PMID- 27396419 TI - Sponsors. PMID- 27396420 TI - Programme. PMID- 27396421 TI - Board RBSS. PMID- 27396422 TI - Belgian Surgical Weeks. PMID- 27396423 TI - Abstracts of Free Papers. PMID- 27396424 TI - Abstracts of Short Communications. PMID- 27396425 TI - Abstracts of Video Free Papers. PMID- 27396426 TI - Abstracts of Lectures. PMID- 27396427 TI - DNA repair gene polymorphisms in non-small-cell lung cancer patients treated with first-line platinum-containing chemotherapy. AB - PURPOSE: Single nucleotide polymorphisms (SNPs) in the DNA repair genes are believed to contribute to the clinical outcome of patients receiving platinum based chemotherapy. We investigated the impact of 2 SNPs of excision repair cross complementation group 1 and 2 of xeroderma pigmentosum complementation group G on the outcome in patients with non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy. METHODS: Between October 2007 and March 2012, we collected 374 blood samples from consecutive patients registered in the TAILOR trial. Four SNPs (rs11615, rs3212986, rs17655, rs1047768) were genotyped using real-time polymerase chain reaction. RESULTS: The rs11615 polymorphism was associated with histotype (p = 0.0123). No other correlations were found with clinical variables or with EGFR or KRAS mutational status. None of the SNPs had any impact on overall survival or progression-free survival. CONCLUSIONS: The findings suggest that the investigated SNPs do not make any significant contribution to the outcome of NSCLC. PMID- 27396428 TI - Evaluation of the adjunctive effect of platelet-rich fibrin to enamel matrix derivative in the treatment of intrabony defects. Six-month results of a randomized, split-mouth, controlled clinical study. AB - AIM: This study aimed to compare the results obtained with enamel matrix derivative (EMD) and EMD + platelet-rich fibrin (PRF) in the treatment of intrabony defects (IBDs) in chronic periodontitis patients. MATERIALS AND METHODS: Using a split-mouth design, 28 paired IBDs were randomly treated either with EMD or with EMD + PRF. Clinical and radiographic measurements including clinical attachment level (CAL), probing depth (PD), gingival recession (GR), defect depth (DD), defect width (DW) and defect angle (DA) were recorded at baseline (BL) and at six months following therapy. RESULTS: BL clinical and radiographic measurements were similar for EMD and EMD + PRF groups. Although postsurgical measurements revealed significant reduction for PD and CAL in both groups, no intergroup difference was detected. When EMD and EMD + PRF groups were compared, defect fill was not also statistically different. CONCLUSIONS: Both therapies resulted in significant clinical improvement in IBD treatment. Addition of PRF did not improve the clinical and radiographic outcomes. PMID- 27396429 TI - Inflammatory response during slow- and fast-twitch muscle regeneration. AB - INTRODUCTION: Skeletal muscles are characterized by their unique ability to regenerate. Injury of a so-called fast-twitch muscle, extensor digitorum longus (EDL), results in efficient regeneration and reconstruction of the functional tissue. In contrast, slow-twitch muscle (soleus) fails to properly reconstruct and develops fibrosis. This study focuses on soleus and EDL muscle regeneration and associated inflammation. METHODS: We determined differences in the activity of neutrophils and M1 and M2 macrophages using flow cytometry and differences in the levels of proinflammatory cytokines using Western blotting and immunolocalization at different times after muscle injury. RESULTS: Soleus muscle repair is accompanied by increased and prolonged inflammation, as compared to EDL. The proinflammatory cytokine profile is different in the soleus and ED muscles. CONCLUSIONS: Muscle repair efficiency differs by muscle fiber type. The inflammatory response affects the repair efficiency of slow- and fast-twitch muscles. Muscle Nerve 55: 400-409, 2017. PMID- 27396430 TI - Expression of G Protein-coupled Receptor 56 Is an Unfavorable Prognostic Factor in Osteosarcoma Patients. AB - G protein-coupled receptor 56 (GPR56) is an atypical G protein-coupled receptor, with the long extracellular N-terminus. GPR56 can trigger various downstream signaling responsible for cell survival, proliferation, adhesion, and migration. Expression of GPR56 is associated with cell malignant transformation and tumor cell metastasis in several carcinomas such as melanoma and glioma. Osteosarcoma is the most common malignant bone tumor in adolescents and young adults with high metastasis tendency. The overall survival of osteosarcoma is unsatisfied, partially due to the lacking of predictive markers for metastasis and overall prognosis. This study aimed at figuring out whether expression of the GPR56 was associated with clinicopathological features of osteosarcoma. Eighty-nine patients who received osteosarcoma operation between March 2004 and February 2011 in Linyi People's Hospital were recruited. Immunohistochemical staining (IHC) was carried out to identify the expression of GPR56 in those osteosarcoma tissues, and our cohort was divided into higher-expression group and lower-expression group according to the cut-off of IHC score. Expression of GPR56 in osteosarcoma tissues was correlated with the TNM stage and overall survival. Univariate and multivariate analysis showed that GPR56 could act as an independent prognosis factor for osteosarcoma. Western blot results demonstrated that GPR56-siRNA down regulated the expression of GTP-RhoA and Ki67. GTP-RhoA participates in the cell migration process, while Ki67 plays important roles in cell proliferation, indicating GPR56 may function in tumor development. Correspondingly, we show that GPR56 regulates the proliferation and invasion capacity of osteosarcoma cells. Our study has revealed the prognostic value of GPR56 expression in osteosarcoma. PMID- 27396431 TI - Differential Regulation of Plasma Copeptin Levels in Patients with Heart Failure: A Single-Center Prospective Study. AB - Elevated levels of arginine vasopressin (AVP) have been reported to be involved in the pathogenesis of heart failure (HF). Recent evidence has shown the role of copeptin, the C-terminal fragment of pro-AVP, as a biomarker in patients with HF. However, the relevant information is still limited. Therefore, we evaluated 39 Japanese patients admitted for HF between 2013 and 2015 (23 males and 16 females with an average age of 79.2 years). They were treated according to the Japanese acute HF guideline. Plasma copeptin levels were measured on admission and about 1 week later. The median plasma copeptin levels on admission were 0.5 (0.1-50.6) pmol/L, higher than the normal values (0.24 +/- 0.06 pmol/L). Despite the similar clinical severity on admission, the patients showed great variability in plasma copeptin levels. They were divided into three groups (13 patients/group) according to plasma copeptin levels on admission: highest (> 30.8 pmol/L), midrange, and lowest (< 0.2 pmol/L) groups. Initial treatment improved HF symptoms in 37 of 39 patients, with the two unresponsive patients in the lowest group. Notably, plasma copeptin responses to initial treatment were different, depending on admission copeptin levels. The initial treatment significantly decreased copeptin levels in the highest group, but increased copeptin levels in the lowest group. By contrast, patients in the midrange group showed no significant changes. Thus, the treatment appears to restore the plasma copeptin levels. In conclusion, HF is a complex syndrome with the differential integration of stimulatory and inhibitory inputs to the AVP/copeptin secretory system. PMID- 27396432 TI - Psychosomatic effects of blanketing in nursing care. AB - AIM: Blanketing, which involves covering patients with a blanket in order to maintain their body temperature and privacy and help alleviate the stress that is associated with medical procedures, is a fundamental skill in nursing care. However, the actual therapeutic effects of blanketing have not been adequately investigated. Therefore, the aim of the present study was to clarify the psychosomatic effects of blanketing in nursing care by observing autonomic nervous activity. METHODS: This single-cohort, intra-participant, comparative cross-over study included 30 healthy female adolescents. Two of the 30 participants were excluded from the analysis. After splitting the participants into blanketing and non-blanketing groups, the stress and anxiety that patients undergo during nursing care was simulated and the responses were analyzed by using psychological and physiological indicators. The parametric data were analyzed by using a paired t-test or one-way ANOVA and the non-parametric data were analyzed by using the Wilcoxon signed-rank test. The significance level was <5%. RESULTS: No significant difference was seen between the two groups in vital signs, salivary alpha-amylase activity, respiratory movement or skin surface temperature. However, the postintervention scores for "Tension-Anxiety" in the Profile of Mood States - Brief Form were significantly lower for the blanketed than the non-blanketed arm, "sense of ease" and "feeling protected" were significantly higher for the blanketed arm, and in the middle intervention segment, the parasympathetic nervous activity and sympathetic nervous activity were significantly higher and lower, respectively, for the blanketed arm. CONCLUSION: These results suggest that blanketing is effective in relieving psychological stress and promoting a sense of ease among patients who are receiving nursing care. PMID- 27396433 TI - IkappaB kinasealpha/beta control biliary homeostasis and hepatocarcinogenesis in mice by phosphorylating the cell-death mediator receptor-interacting protein kinase 1. AB - The IkappaB-Kinase (IKK) complex-consisting of the catalytic subunits, IKKalpha and IKKbeta, as well as the regulatory subunit, NEMO-mediates activation of the nuclear factor kappaB (NF-kappaB) pathway, but previous studies suggested the existence of NF-kappaB-independent functions of IKK subunits with potential impact on liver physiology and disease. Programmed cell death is a crucial factor in the progression of liver diseases, and receptor-interacting kinases (RIPKs) exerts strategic control over multiple pathways involved in regulating novel programmed cell-death pathways and inflammation. We hypothesized that RIPKs might be unrecognized targets of the catalytic IKK-complex subunits, thereby regulating hepatocarcinogenesis and cholestasis. In this present study, mice with specific genetic inhibition of catalytic IKK activity in liver parenchymal cells (LPCs; IKKalpha/beta(LPC-KO) ) were intercrossed with RIPK1(LPC-KO) or RIPK3(-/-) mice to examine whether RIPK1 or RIPK3 might be downstream targets of IKKs. Moreover, we performed in vivo phospho-proteome analyses and in vitro kinase assays, mass spectrometry, and mutagenesis experiments. These analyses revealed that IKKalpha and IKKbeta-in addition to their known function in NF-kappaB activation-directly phosphorylate RIPK1 at distinct regions of the protein, thereby regulating cell viability. Loss of this IKKalpha/beta-dependent RIPK1 phosphorylation in LPCs inhibits compensatory proliferation of hepatocytes and intrahepatic biliary cells, thus impeding HCC development, but promoting biliary cell paucity and lethal cholestasis. CONCLUSIONS: IKK-complex subunits transmit a previously unrecognized signal through RIPK1, which is fundamental for the long-term consequences of chronic hepatic inflammation and might have potential implications for future pharmacological strategies against cholestatic liver disease and cancer. (Hepatology 2016;64:1217-1231). PMID- 27396434 TI - Are stroke survivors with delirium at higher risk of post-stroke dementia? Current evidence and future directions. AB - OBJECTIVES: The idea that delirium is a risk factor for dementia, broadly defined, is derived from heterogeneous patient samples. We reviewed available evidence as to whether stroke survivors who developed delirium during the acute phase of treatment are at a higher prospective risk of incident post-stroke cognitive impairment or dementia. DESIGN: We searched 8721 records in the Cochrane database for reviews or protocols dealing with the study objective, Medline, EMBASE, PsycInfo and CINAHL for observational studies in the general adult population and PubMed for in-process articles. Additional searches of the reference lists of retrieved articles were also undertaken. Qualitative syntheses and meta-analysis were conducted according to conventional guidelines. RESULTS: Twelve relevant articles were fully appraised. Four out of these studies, comprising 743 stroke survivors, including 199 with delirium, met criteria for qualitative syntheses. Overall, the studies presented low to moderate level evidence suggesting an association between post-stroke delirium and dementia. CONCLUSIONS: There is a need for further studies to investigate the association of post-stroke delirium and dementia using well-defined cohorts of patients and controlling for factors such as pre-stroke cognition, stroke severity and location and the presence of persistent delirium. Such studies will help understand the place of delirium identification and prevention in reducing the risk of dementia after stroke. (c) 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd. PMID- 27396435 TI - Seizure outcome after switching antiepileptic drugs: A matched, prospective study. AB - OBJECTIVE: Outcomes after changing antiepileptic drugs (AEDs) have largely been studied in single cohort series. We recently reported the first study to examine this question in a controlled manner. Here we expand on these results by using a matched, prospective methodology applied to both uncontrolled and well-controlled patients taking any AED. METHODS: We reviewed all outpatient notes over a 9-month period and identified patients with focal epilepsy who were on monotherapy. We classified those who switched AEDs as case patients, with those remaining on the same drug serving as controls. We matched cases with controls for seizure status (seizure-free in the preceding 6 months or not), current AED, and number of failed AEDs. We subsequently assessed outcome 6 months later. RESULTS: Seizure free patients who switched drug (n = 12) had a 16.7% rate of seizure recurrence at 6 months, compared to 2.8% among controls remaining on the same drug (n = 36, p = 0.11). There was a 37% remission rate among uncontrolled patients who switched drug compared to 55.6% among controls (n = 27 per group, p = 0.18). Uncontrolled patients who had previously tried more than one AED were somewhat less likely to enter remission (p = 0.057). Neither AED mechanism of action nor change in dosage impacted outcome. SIGNIFICANCE: Herein we provide further estimation of the modest risk (~14%) associated with switching AEDs in patients in remission compared to being maintained on the same regimen. Uncontrolled patients were no more likely to enter remission after a drug switch than they were after remaining on the same drug, suggesting that spontaneous changes in disease state, and not drug response, underlie remission in this population. PMID- 27396436 TI - Commonly Employed African Neonatal Skin Care Products Compromise Epidermal Function in Mice. AB - BACKGROUND: Neonatal mortality is much higher in the developing world than in developed countries. Infections are a major cause of neonatal death, particularly in preterm infants, in whom defective epidermal permeability barrier function facilitates transcutaneous pathogen invasion. The objective was to determine whether neonatal skin care products commonly used in Africa benefit or compromise epidermal functions in murine skin. METHODS: After twice-daily treatment of 6- to 8-week-old hairless mice with each skin care product for 3 days, epidermal permeability barrier function, skin surface pH, stratum corneum hydration, and barrier recovery were measured using a multiprobe adapter system physiology monitor. For products showing some benefits in these initial tests, the epidermal permeability barrier homeostasis was assessed 1 and 5 hours after a single application to acutely disrupted skin. RESULTS: All of the skin care products compromised basal permeability barrier function and barrier repair kinetics. Moreover, after 3 days of treatment, most of the products also reduced stratum corneum hydration while elevating skin surface pH to abnormal levels. CONCLUSION: Some neonatal skin care products that are widely used in Africa perturb important epidermal functions, including permeability barrier homeostasis in mice. Should these products have similar effects on newborn human skin, they could cause a defective epidermal permeability barrier, which can increase body fluid loss, impair thermoregulation, and contribute to the high rates of neonatal morbidity and mortality seen in Africa. Accordingly, alternative products that enhance permeability barrier function should be identified, particularly for use in preterm infants. PMID- 27396437 TI - Logistical difficulties in surgical research. PMID- 27396438 TI - The Resilience of Women: Atrial Fibrillation Resistance. PMID- 27396439 TI - Laser Ablation - Accelerator Mass Spectrometry: An Approach for Rapid Radiocarbon Analyses of Carbonate Archives at High Spatial Resolution. AB - A new instrumental setup, combining laser ablation (LA) with accelerator mass spectrometry (AMS), has been investigated for the online radiocarbon ((14)C) analysis of carbonate records. Samples were placed in an in-house designed LA cell, and CO2 gas was produced by ablation using a 193 nm ArF excimer laser. The (14)C/(12)C abundance ratio of the gas was then analyzed by gas ion source AMS. This configuration allows flexible and time-resolved acquisition of (14)C profiles in contrast to conventional measurements, where only the bulk composition of discrete samples can be obtained. Three different measurement modes, i.e. discrete layer analysis, survey scans, and precision scans, were investigated and compared using a stalagmite sample and, subsequently, applied to terrestrial and marine carbonates. Depending on the measurement mode, a precision of typically 1-5% combined with a spatial resolution of 100 MUm can be obtained. Prominent (14)C features, such as the atomic bomb (14)C peak, can be resolved by scanning several cm of a sample within 1 h. Stalagmite, deep-sea coral, and mollusk shell samples yielded comparable signal intensities, which again were comparable to those of conventional gas measurements. The novel LA-AMS setup allowed rapid scans on a variety of sample materials with high spatial resolution. PMID- 27396441 TI - Deletion of CD28 Co-stimulatory Signals Exacerbates Left Ventricular Remodeling and Increases Cardiac Rupture After Myocardial Infarction. AB - BACKGROUND: Inflammatory responses, especially by CD4(+)T cells activated by dendritic cells, are known to be important in the pathophysiology of cardiac repair after myocardial infarction (MI). Although co-stimulatory signals through B7 (CD80/86) and CD28 are necessary for CD4(+)T cell activation and survival, the roles of these signals in cardiac repair after MI are still unclear. METHODS AND RESULTS: C57BL/6 (Control) mice and CD28 knockout (CD28KO) mice were subjected to left coronary artery permanent ligation. The ratio of death by cardiac rupture within 5 days after MI was significantly higher in CD28KO mice compared with Control mice. Although there were no significant differences in the infarct size between the 2 groups, left ventricular end-diastolic and end-systolic diameters were significantly increased, and fractional shortening was significantly decreased in CD28KO mice compared with Control mice. Electron microscopic observation revealed that the extent of extracellular collagen fiber was significantly decreased in CD28KO mice compared with Control mice. The number of alpha-smooth muscle actin-positive myofibroblasts was significantly decreased, and matrix metalloproteinase-9 activity and the mRNA expression of interleukin 1beta were significantly increased in CD28KO mice compared with Control mice. CONCLUSIONS: Deletion of CD28 co-stimulatory signals exacerbates left ventricular remodeling and increases cardiac rupture after MI through prolongation of the inflammatory period and reduction of collagen fiber in the infarct scars. (Circ J 2016; 80: 1971-1979). PMID- 27396442 TI - Treatment of Spontaneous Isolated Superior Mesenteric Artery Dissection. PMID- 27396440 TI - Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. AB - KEY POINTS: A classic unresolved issue in human integrative physiology involves the role of exercise intensity, duration and volume in regulating skeletal muscle adaptations to training. We employed counterweighted single-leg cycling as a unique within-subject model to investigate the role of exercise intensity in promoting training-induced increases in skeletal muscle mitochondrial content. Six sessions of high-intensity interval training performed over 2 weeks elicited greater increases in citrate synthase maximal activity and mitochondrial respiration compared to moderate-intensity continuous training matched for total work and session duration. These data suggest that exercise intensity, and/or the pattern of contraction, is an important determinant of exercise-induced skeletal muscle remodelling in humans. ABSTRACT: We employed counterweighted single-leg cycling as a unique model to investigate the role of exercise intensity in human skeletal muscle remodelling. Ten young active men performed unilateral graded exercise tests to measure single-leg VO2, peak and peak power (Wpeak ). Each leg was randomly assigned to complete six sessions of high-intensity interval training (HIIT) [4 * (5 min at 65% Wpeak and 2.5 min at 20% Wpeak )] or moderate intensity continuous training (MICT) (30 min at 50% Wpeak ), which were performed 10 min apart on each day, in an alternating order. The work performed per session was matched for MICT (143 +/- 8.4 kJ) and HIIT (144 +/- 8.5 kJ, P > 0.05). Post training, citrate synthase (CS) maximal activity (10.2 +/- 0.8 vs. 8.4 +/- 0.9 mmol kg protein-1 min-1 ) and mass-specific [pmol O2 *(s*mg wet weight)-1 ] oxidative phosphorylation capacities (complex I: 23.4 +/- 3.2 vs. 17.1 +/- 2.8; complexes I and II: 58.2 +/- 7.5 vs. 42.2 +/- 5.3) were greater in HIIT relative to MICT (interaction effects, P < 0.05); however, mitochondrial function [i.e. pmol O2 *(s*CS maximal activity)-1 ] measured under various conditions was unaffected by training (P > 0.05). In whole muscle, the protein content of COXIV (24%), NDUFA9 (11%) and mitofusin 2 (MFN2) (16%) increased similarly across groups (training effects, P < 0.05). Cytochrome c oxidase subunit IV (COXIV) and NADH:ubiquinone oxidoreductase subunit A9 (NDUFA9) were more abundant in type I than type II fibres (P < 0.05) but training did not increase the content of COXIV, NDUFA9 or MFN2 in either fibre type (P > 0.05). Single-leg VO2, peak was also unaffected by training (P > 0.05). In summary, single-leg cycling performed in an interval compared to a continuous manner elicited superior mitochondrial adaptations in human skeletal muscle despite equal total work. PMID- 27396443 TI - Is the Brain the Alternative Therapeutic Target for Heart Failure? PMID- 27396444 TI - Treatment of Spontaneous Isolated Superior Mesenteric Artery Dissection - Reply. PMID- 27396445 TI - B cell-T cell interaction: antigen bridge to antigen presentation. PMID- 27396448 TI - Electrically Conductive Diamond Membrane for Electrochemical Separation Processes. AB - Electrochemically switchable selective membranes play an important role in selective filtration processes such as water desalination, industrial waste treatment, and hemodialysis. Currently, membranes for these purposes need to be optimized in terms of electrical conductivity and stability against fouling and corrosion. In this paper, we report the fabrication of boron-doped diamond membrane by template diamond growth on quartz fiber filters. The morphology and quality of the diamond coating are characterized via SEM and Raman spectroscopy. The membrane is heavily boron doped (>10(21) cm(-3)) with >3 V potential window in aqueous electrolyte. By applying a membrane potential against the electrolyte, the redox active species can be removed via flow-through electrolysis. Compared to planar diamond electrodes, the ~250 times surface enlargement provided by such a membrane ensures an effective removal of target chemicals from the input electrolyte. The high stability of diamond enables the membrane to not only work at high membrane bias but also to be self-cleaning via in situ electrochemical oxidation. Therefore, we believe that the diamond membrane presented in this paper will provide a solution to future selective filtration applications especially in extreme conditions. PMID- 27396449 TI - Coming in postgraduate medicine. PMID- 27396446 TI - Immunity by equilibrium. AB - The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology. PMID- 27396450 TI - Problems/Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27396447 TI - A guide to immunometabolism for immunologists. AB - In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease. PMID- 27396451 TI - What's Happening in Medicine! PMID- 27396452 TI - Washington Report on Health. PMID- 27396453 TI - Medical Evaluation by Bioelectric Impedance. PMID- 27396455 TI - Audiovisuals. PMID- 27396454 TI - Introduction. PMID- 27396456 TI - Meetings & courses. PMID- 27396458 TI - Personal business. PMID- 27396460 TI - Neck or groin access for varicocele embolisation: Is it important? AB - INTRODUCTION: Varicocele embolisation is an excellent treatment option for symptomatic scrotal varicosities. The purpose of this study was to assess the current practice of the endovascular treatment of left-sided varicoceles at our institution, to compare the findings to international standards and to identify which access site reduces screening time and radiation dose. METHODS: All left sided varicocele embolisations over a 4-year period were identified and analysed with regards to technical success, complications and recurrence rates. The results were analysed with regard to the encountered anatomy on a case-to-case basis to identify anatomical factors influencing the outcome of the procedure. RESULTS: During the study period 95 primary left-sided varicocele embolisations were performed by two experienced consultants. Five cases had a normal initial venogram (Type 0) and further five had unsuitable anatomy for embolisation. Eighty-three of the remaining 85 attempted embolisations were technically successful (98% technical success rate). The clinical success rate was determined by recurrence, which was documented in five cases (mean follow-up 34.3 month, 6% recurrence rate). Recurrence was associated with more complex local anatomy (Type 3 and Type 4). The overall findings were consistent with international published standards for technical success rate (95-100%) and recurrence rates (1.6-10%). Complication rates were low with extravasation being reported in 4.7% (all self limiting) and temporary pain in 3.5% of the cases. There was no significant difference in radiation dose/screening time, success or complications when comparing a groin versus neck approach to the embolisation procedure (P > 0.05). CONCLUSIONS: Varicocele embolisation is successful with a low complications rate. Neck and groin access are equally successful with no significant difference in screening time. PMID- 27396461 TI - Treating tobacco companies fairly but with no leap of faith. PMID- 27396462 TI - Commentary on Singh et al. (2016): Still searching for the answer. PMID- 27396463 TI - Commentary on Ilgen et al. (2016): Integrating chronic pain programs into addiction treatment-full steam ahead. PMID- 27396464 TI - Commentary on Brunborg et al. (2016): Personality research allows for a better understanding of the etiology and treatment of addictive behaviors. PMID- 27396465 TI - Correcting the record on NCRG-funded research. PMID- 27396466 TI - The NCRG Firewall Works. PMID- 27396467 TI - Reply to Cottler et al.'s Letter to the Editor. PMID- 27396468 TI - Reply to Cottler et al. (2016): The NCRG firewall works more for the gambling industry than for the scientific community. PMID- 27396471 TI - "From Tears to Transparency: A Conversation Can Change an Outcome. A Conversation Can Change a LifeTM ": Reflections From Patient Advocates. AB - The Society for Academic Emergency Medicine (SAEM) consensus conference provided many platforms for patient advocates to share their experiences and demonstrate the powerful contribution they have to offer to the decision-making process. One such platform was the presentation of a film "The Faces of Medical Error: From Tears to Transparency," shared by Patricia (Patty) and David Skolnik. In this article the Skolniks build on their story shared at the SAEM consensus conference and panel discussion. They provide further insight drawn from 9 years of experience as advocates for patient safety, including their reflections on working with, training, and educating medical professionals, lawmakers, and consumers in shared decision making and informed consent. PMID- 27396472 TI - 16-Channel Organic Electrochemical Transistor Array for In Vitro Conduction Mapping of Cardiac Action Potential. AB - 16-Channel organic electrochemical transistor arrays (OECTs) are developed for mapping the propagation and studying the characteristics of action potentials of primary cardiomyocytes. The physiological activities of a rat cardiomyocyte monolayer during a long-term culturing is revealed by this biocompatible, low cost, and high transconductance organic electronic device. OECT has great potential to be used in cardiac and neuronal drug screening. PMID- 27396473 TI - Inconsistencies and time delays in site-specific research approvals hinder collaborative clinical research in Australia. AB - BACKGROUND/AIM: The aim of this study was to describe the time and documentation needed to gain ethics and governance approvals in Australian states with and without a centralised ethical review system. METHODS: This is a prospective descriptive study undertaken between February 2012 and March 2015. Paediatric and adult hospitals (n = 67) in Australian states were approached to allow the review of their medical records. Participants included 15- to 24-year-olds diagnosed with cancer between 2008 and 2012. The main outcomes measures were time (weeks) to approval for ethics and governance and the number and type of documents submitted. RESULTS: Centralised ethics approval processes were used in five states, with approval taking between 2 and 18 weeks. One state did not use a centralised process, with ethics approval taking a median of 4.5 weeks (range: 0 15) per site. In four states using a centralised ethics process, 33 governance applications were submitted, with 20 requiring a site clinician listed as an investigator. Governance applications required the submission of 11 documents on average, including a Site-Specific Assessment form. Thirty-two governance applications required original signatures from a median of 3.5 (range: 1-10) non research persons, which took a median of 5 weeks (range: 0-15) to obtain. Governance approval took a median of 6 weeks (range: 1-45). Twelve research study agreements were needed, each taking a median of 7.5 weeks (range: 1-20) to finalise. CONCLUSION: The benefits of centralised ethics review systems have not been realised due to duplicative, inflexible governance processes. A system that allowed the recognition of prior ethical approval and low-risk applications was more efficient than a central ethics and site-specific governance process. PMID- 27396474 TI - A prospective randomised trial comparing insertion success rate and incidence of catheterisation-related complications for subclavian venous catheterisation using a thin-walled introducer needle or a catheter-over-needle technique. AB - In clinical practice, both a thin-walled introducer needle and catheter-over needle technique can be used to allow insertion of a guidewire during central venous catheterisation using the Seldinger technique. We compared the incidence of catheterisation-related complications (arterial puncture, haemothorax, pneumothorax, haematoma and catheter tip malposition) and insertion success rate for these two techniques in patients requiring right-sided subclavian central venous catheterisation. A total of 414 patients requiring infraclavicular subclavian venous catheterisation were randomly allocated to either a thin-walled introducer needle (needle group, n = 208) or catheter-over-needle technique (catheter group, n = 206). The catheterisation-related complication rate was lower in the needle group compared with the catheter group (5.8% vs. 15.5%; p = 0.001). Overall insertion success rates were similar (97.1% and 92.7% in the needle and catheter groups respectively; p = 0.046), although the first-pass success rate was higher in the needle group (62.0% vs. 35.4%; p < 0.001). We recommend the use of a thin-walled introducer needle technique for right-sided infraclavicular subclavian venous catheterisation. PMID- 27396475 TI - Quantum chemical modeling of magnetically bistable metal coordination compounds. Synchronization of spin crossover, valence tautomerism and charge transfer induced spin transition mechanisms. AB - It has been shown that the computationally designed bimetallic complexes formed as the adducts of Co(II) diketonates and salicylaldiminates with Fe(II) chelates of 1,10-phenanthroline-5,6-dione are susceptible to the synchronized thermally induced intramolecular rearrangements between their electromeric forms LSCo(III) SQ-LSFe(II), LSCo(III)-SQ-HSFe(II), HSCo(II)-BQ-LSFe(II), HSCo(II)-BQ-HSFe(II) and also HSCo(II)-SQ-LSFe(III), which are governed by the spin-crossover (SCO), valence tautomerism (VT) and charge-transfer-induced spin transition (CTIST) mechanisms of spin-state switching. Stability of the adducts with respect to dissociation into components, relative energies and magnetic properties of the electromers and energy barriers against VT and unprecedented one-step (SCO + VT) rearrangements (estimated as minimum energy crossing points on the seams of the intersection of the corresponding potential energy surfaces) were calculated using the DFT (B3LYP*/6-311++G(d,p)) method. The calculations showed that all these characteristics of the system as well as the energy preferred spin-state switchable mechanisms are very sensitive to the structure of the cobalt diketonate (salicylaldiminate) fragment and can be varied and interchanged by the introduction of electron withdrawing substituents into the ligands. PMID- 27396476 TI - Uptake and retention of manganese contrast agents for PET and MRI in the rodent brain. AB - Manganese-enhanced magnetic resonance imaging (MRI) is an established neuroimaging method for signal enhancement, tract tracing, and functional studies in rodents. Along with the increasing availability of combined positron emission tomography (PET) and MRI scanners, the recent development of the positron emitting isotope 52 Mn has prompted interest in the use of Mn2+ as a dual modality contrast agent. In this work, we characterized and compared the uptake of systemically delivered Mn2+ and radioactive 52 Mn2+ in the rat brain for MRI and PET, respectively. Additionally, we examined the biodistribution of two formulations of 52 Mn2+ in the rat. In MRI, maximum uptake was observed one day following delivery of the highest MnCl2 dose tested (60 mg/kg), with some brain regions showing delayed maximum enhancement 2-4 days following delivery. In PET, we observed low brain uptake after systemic delivery, with a maximum of approximately 0.2% ID/g. We also studied the effect of final formulation vehicle (saline compared with MnCl2 ) on 52 Mn2+ organ biodistribution and brain uptake. We observed that the addition of bulk Mn2+ carrier to 52 Mn2+ in solution resulted in significantly reduced 52 Mn2+ uptake in the majority of organs, including the brain. These results lay the groundwork for further development of 52 Mn PET or dual Mn-enhanced PET-MR neuroimaging in rodents, and indicate several interesting potential applications of 52 Mn PET in other organs and systems. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27396477 TI - Parkinson's Disease, Diabetes and Cognitive Impairment. AB - BACKGROUND: Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. OBJECTIVE: To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. METHOD: A narrative review using MEDLINE database. RESULTS: Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. CONCLUSION: Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise. PMID- 27396478 TI - Affective brain-computer music interfacing. AB - OBJECTIVE: We aim to develop and evaluate an affective brain-computer music interface (aBCMI) for modulating the affective states of its users. APPROACH: An aBCMI is constructed to detect a user's current affective state and attempt to modulate it in order to achieve specific objectives (for example, making the user calmer or happier) by playing music which is generated according to a specific affective target by an algorithmic music composition system and a case-based reasoning system. The system is trained and tested in a longitudinal study on a population of eight healthy participants, with each participant returning for multiple sessions. MAIN RESULTS: The final online aBCMI is able to detect its users current affective states with classification accuracies of up to 65% (3 class, [Formula: see text]) and modulate its user's affective states significantly above chance level [Formula: see text]. SIGNIFICANCE: Our system represents one of the first demonstrations of an online aBCMI that is able to accurately detect and respond to user's affective states. Possible applications include use in music therapy and entertainment. PMID- 27396479 TI - Surfactant-Stripped Frozen Pheophytin Micelles for Multimodal Gut Imaging. AB - Edible, surfactant-stripped, frozen micelles are formed from pheophytin (demetallated chlorophyll), a pigment that is naturally consumed in human diets. Pheophytin nanoparticles pass completely and safely through the gastrointestinal tract and enable trimodal gut contrast imaging via photoacoustic, fluorescence, and positron emission tomography techniques. PMID- 27396480 TI - Assessment of "corticophobia" as an indicator of non-adherence to topical corticosteroids: A pilot study. AB - BACKGROUND: Concerns regarding topical corticosteroid (TCS) use, broadly known as "corticophobia", are highly prevalent among dermatology patients and often result in non-adherence to TCS. This non-adherence contributes to poor disease control and increased health care costs. However, it is unknown if assessment of these concerns might help to identify patients at risk of TCS-non-adherence. Clinical tools indicating non-adherence could be helpful to improve management of this patient group. OBJECTIVE: To assess whether the available tools for measuring concerns regarding corticosteroids, the TOPICOP scale and the 0-10 Visual Analogue Scale (VAS), could help to detect non-adherence to TCS. METHODS: In 75 patients with concerns regarding TCS use both the TOPICOP scale and VAS were anonymously assessed. A comparison was made between TCS-adherent and non-adherent patients regarding the intensity and characteristics of their concerns. RESULTS: The intensity and quality of the concerns varied broadly among the patients. When using the VAS, a score of >=5 detected 87% of non-adherent patients. The answers to the TOPICOP scale did not discriminate non-adherent from adherent patients. CONCLUSION: Using the VAS to assess concerns to use TCS could help identify patients at risk of TCS-non-adherence and facilitate discussion with the patient about potential non-adherence in a more substantiated, non-judgemental way. PMID- 27396481 TI - Validation of a biotherapeutic immunoaffinity-LC-MS/MS assay in monkey serum: 'plug-and-play' across seven molecules. AB - BACKGROUND: Biotherapeutics development requires validated assays in biological matrices for pharmacokinetic assessment. Historically, ligand-binding assays have been the predominant platform available. Recently, alternative hybrid methods, combining ligand-binding analyte enrichment with LC-MS detection have emerged. Methodology & results: The validation of an immunoaffinity (IA)-LC-MS/MS method to quantify a monoclonal antibody biotherapeutic in cynomolgus monkey serum is described. This method includes immunoaffinity capture of the antibody in serum, followed by enzymatic digestion and detection of a framework peptide. Using similar method conditions, six additional biotherapeutic assays were readily validated in different nonhuman mammalian species, including mouse, rat and monkey. CONCLUSION: The immunoaffinity-LC-MS/MS assay validation results across seven antibody therapeutics, using comparable conditions, illustrate the 'plug and-play' nature of the IA-LC-MS/MS mAb framework peptide assay format. PMID- 27396482 TI - NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment. AB - Shelterin component TPP1 plays critical roles in chromosome end protection and telomere length regulation. Specifically, TPP1 contains an OB-fold domain that provides an interface to recruit telomerase. However, it remains largely unknown how telomerase recruitment is regulated by cell cycle regulators. We show that TPP1 interacts with the cell cycle regulator kinase NEK6 in human cells. We found that NEK6-mediated phosphorylation of TPP1 Ser255 in G2/M phase regulates the association between telomerase activity and TPP1. Furthermore, we found evidence that POT1 negatively regulates TPP1 phosphorylation because the level of Ser255 phosphorylation was elevated when telomeres were elongated by a POT1 mutant lacking its OB-fold domains. Ser255 is located in the intervening region between the telomerase-recruiting OB-fold and the POT1 recruitment domains. Ser255 and the surrounding amino acids are conserved among vertebrates. These observations suggest that a region adjacent to the OB-fold domain of TPP1 is involved in telomere length regulation via telomerase recruitment. PMID- 27396483 TI - Electrooptical Absorption Measurements (EOAM) Testify Existence of two Conformers of Prodan and Laurdan with Different Dipole Moments in Equilibrium Ground and Franck-Condon Excited State. AB - The results from the electrooptical absorption measurements (EOAM) on the equilibrium ground and excited Franck-Condon state dipole moments of Prodan and Laurdan in 1,4-dioxane are presented. As follows from experiments Prodan and Laurdan in the equilibrium ground and excited Franck-Condon state have two conformers with considerably different dipole moments. The electrical dipole moments and the transition dipole moment, obtained from the short-wavelength region of the absorption spectrum are parallel. The electrical dipole moments measured at the long-wavelength spectral region are parallel to each other but not parallel to the transition dipole moment m a. The angle theta between the transition dipole moment m a and the dipole moment in the equilibrium ground state MU g of the long-wavelength conformer is about 30(0) for both probes. Obtained results evidence that donor-acceptor pairs of the short-wavelength and long-wavelength conformers are not located on the same axis. Two low-energy conformers of Prodan have been found by density functional theory (DFT) calculations, differing in the orientation of the carbonyl group towards the naphthalene system. PMID- 27396484 TI - Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program. AB - BACKGROUND: The outpatient therapeutic care program (OTP) of children with severe acute malnutrition (SAM) has been decentralized to health post level in Ethiopia since 2008-2009. However, there is a lack of evidence regarding treatment outcomes and factors related to the duration of stay on treatment after its decentralization to health post level. OBJECTIVE: This study was aimed to assess treatment outcome and factors affecting time to recovery in children with SAM treated at OTP. DESIGN: Health facility-based retrospective cohort study was conducted using data from 348 patient cards. The outcome variable was time to recovery. Descriptive analysis was done using percentages for categorical data and mean/median for continuous variables. A robust method of analyzing time to event data, the Cox proportional-hazard regression, was used. All statistical tests in this study are declared significant at p<0.05. RESULT: 89.1% of children with kwashiorkor and 69.4% of children with marasmus were recovered. Of the total children studied, 22% were readmitted cases. The median time of recovery was 35 days for children with kwashiorkor and 49 days for children with marasmus. Children older than 3 years were 33% less likely to achieve nutritional recovery [adjusted hazard ratio, AHR=0.67, 95% confidence interval, CI (0.46, 0.97)]. Similarly, marasmic children stayed longer on treatment [AHR=0.42, 95% CI (0.32, 0.56)]. However, children who gained Mid-Upper Arm Circumference (MUAC) >= 0.24 mm/day were 59% more likely to recover faster [AHR=1.59, 95% CI (1.23, 2.06)]. CONCLUSIONS: Close monitoring of weight and MUAC gain to assess nutritional improvement with due emphasis given to children with lower admission weight, children of age 3 years and above and marasmic children will have a positive effect on treatment duration and outcome. PMID- 27396485 TI - Informing road traffic intervention choices in South Africa: the role of economic evaluations. AB - INTRODUCTION: Given the burden of road traffic injuries (RTIs) in South Africa, economic evaluations of prevention interventions are necessary for informing and prioritising public health planning and policy with regard to road safety. METHODS: In view of the dearth of RTI cost analysis, and in order to understand the extent to which RTI-related costs in South Africa compare with those in other low- and middle-income countries (LMICs), we reviewed published economic evaluations of RTI-related prevention in LMICs. RESULTS: Thirteen articles were identified, including cost-of-illness and cost-effectiveness studies. Although RTI-related risk factors in South Africa are well described, costing studies are limited. There is minimal information, most of which is not recent, with nothing at all on societal costs. Cost-effective interventions for RTIs in LMICs include bicycle and motorcycle helmet enforcement, traffic enforcement, and the construction of speed bumps. DISCUSSION: Policy recommendations from studies conducted in LMICs suggest a number of cost-effective interventions for consideration in South Africa. They include speed bumps for pedestrian safety, strategically positioned speed cameras, traffic enforcement such as the monitoring of seatbelt use, and breathalyzer interventions. However, interventions introduced in South Africa will need to be based either on South African cost-effectiveness data or on findings adapted from similar middle-income country settings. PMID- 27396486 TI - In-plane graphene/boron-nitride heterostructures as an efficient metal-free electrocatalyst for the oxygen reduction reaction. AB - Exploiting metal-free catalysts for the oxygen reduction reaction (ORR) and understanding their catalytic mechanisms are vital for the development of fuel cells (FCs). Our study has demonstrated that in-plane heterostructures of graphene and boron nitride (G/BN) can serve as an efficient metal-free catalyst for the ORR, in which the C-N interfaces of G/BN heterostructures act as reactive sites. The formation of water at the heterointerface is both energetically and kinetically favorable via a four-electron pathway. Moreover, the water formed can be easily released from the heterointerface, and the catalytically active sites can be regenerated for the next cycle. Since G/BN heterostructures with controlled domain sizes have been successfully synthesized in recent reports (e.g. Nat. Nanotechnol., 2013, 8, 119), our results highlight the great potential of such heterostructures as a promising metal-free catalyst for the ORR in FCs. PMID- 27396487 TI - Evaluation of an amide-based stationary phase for supercritical fluid chromatography. AB - A relatively new stationary phase containing a polar group embedded in a hydrophobic backbone (i.e., ACE(r)C18-amide) was evaluated for use in supercritical fluid chromatography. The amide-based column was compared with columns packed with bare silica, C18 silica, and a terminal-amide silica phase. The system was held at supercritical pressure and temperature with a mobile phase composition of CO2 and methanol as cosolvent. The linear solvation energy relationship model was used to evaluate the behavior of these stationary phases, relating the retention factor of selected probes to specific chromatographic interactions. A five-component test mixture, consisting of a group of drug-like molecules was separated isocratically. The results show that the C18 -amide stationary phase provided a combination of interactions contributing to the retention of the probe compounds. The hydrophobic interactions are favorable; however, the electron donating ability of the embedded amide group shows a large positive interaction. Under the chromatographic conditions used, the C18 -amide column was able to provide baseline resolution of all the drug-like probe compounds in a text mixture, while the other columns tested did not. PMID- 27396488 TI - Effects of cereal soluble dietary fibres on hydrolysis of p-nitrophenyl laurate by pancreatin. AB - The aim of this study was to investigate the effects of cereal soluble dietary fibres (SDFs), beta-glucans (BG) from oat and barley as well as arabinoxylans (AX) from wheat and rye, on the lipolysis of p-nitrophenyl laurate (p-NP laurate). p-NP laurate emulsions were prepared in the presence of increasing concentrations of SDFs (0.1%, 1.0% and 1.5% w/v), and lipolysis of emulsions by pancreatic lipase, particle size distribution of the p-NP laurate droplets, and viscosity of emulsions with soluble dietary fibres were measured. It was found that with increasing viscosity of SDFs, the rate of lipolysis decreased while the initial droplet size of the emulsion increased. Rate coefficients were more consistently correlated with average droplet size than with viscosity, suggesting that SDFs inhibited lipolysis primarily by increasing the size of droplets through flocculation, thereby decreasing the available surface area for lipase action. PMID- 27396489 TI - Advancing Drug Formulation Additives toward Precision Additives with Release Mediating Peptide Interlayer. AB - Amphiphilic drug formulation additives based on palmitic acid-modified poly(ethylene glycol) (Pal-PEG) are combined with a tailored drug binding peptide that is positioned at the hydrophobic-hydrophilic interface. The peptide originates from combinatorial selection and enables precise modulation of the drug release profiles. While Pal provides a cost-effective reservoir for drug storage, the PEG realizes solubility and shielding. The precision additives reach high payloads close to 1:1, rendering a photosensitizer water-soluble and providing adjustable drug activation kinetics by fine-tuning the peptide interface layer. PMID- 27396491 TI - Foreword: Developmental Exposure to Environmental Chemicals and Metabolic Changes in Children. PMID- 27396490 TI - Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP 4) Inhibitors for the Treatment of Type 2 Diabetes. AB - Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2 phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 ~ 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented. PMID- 27396492 TI - Contribution of polio eradication initiative to strengthening routine immunization: Lessons learnt in the WHO African region. AB - BACKGROUND: Important investments were made in countries for the polio eradication initiative. On 25 September 2015, a major milestone was achieved when Nigeria was removed from the list of polio-endemic countries. Routine Immunization, being a key pillar of polio eradication initiative needs to be strengthened to sustain the gains made in countries. For this, there is a huge potential on building on the use of polio infrastructure to contribute to RI strengthening. METHODS: We reviewed estimates of immunization coverage as reported by the countries to WHO and UNICEF for three vaccines: BCG, DTP3 (third dose of diphtheria-tetanus toxoid- pertussis), and the first dose of measles containing vaccine (MCV1).We conducted a systematic review of best practices documents from eight countries which had significant polio eradication activities. RESULTS: Immunization programmes have improved significantly in the African Region. Regional coverage for DTP3 vaccine increased from 51% in 1996 to 77% in 2014. DTP3 coverage increased >3 folds in DRC (18-80%) and Nigeria from 21% to 66%; and >2 folds in Angola (41-87%), Chad (24-46%), and Togo (42-87%). Coverage for BCG and MCV1 increased in all countries. Of the 47 countries in the region, 18 (38%) achieved a national coverage for DTP3 ?90% for 2years meeting the Global Vaccine Action (GVAP) target. A decrease was noted in the Ebola affected countries i.e., Guinea, Liberia and Sierra Leone. CONCLUSIONS: PEI has been associated with increased spending on immunization and the related improvements, especially in the areas of micro planning, service delivery, program management and capacity building. Continued efforts are needed to mobilize international and domestic support to strengthen and sustain high quality immunization services in African countries. Strengthening RI will in turn sustain the gains made to eradicate poliovirus in the region. PMID- 27396493 TI - Risk of underlying chronic medical conditions for invasive pneumococcal disease in adults. AB - PURPOSE: In the United States, the 13-valent pneumococcal conjugate vaccine is recommended in persons ?65years of age, and persons ?65years of age with immunocompromising (IC) conditions. For invasive pneumococcal disease (IPD) prevention in those ?65 with non-IC medical conditions, the 23-valent polysaccharide vaccine is recommended. This group is at higher risk of IPD than the general population, but the level of risk is not well-quantified. We estimated IPD risk by individual underlying medical conditions, and by total number of conditions, for persons ?18years of age. We calculated the relative risks (RR) of various medical conditions, comparing the incident IPD cases to the general study population, and used Poisson regression models to estimate an IPD RR, adjusting for other conditions. We also examined IPD incidence by number of conditions diagnosed in each calendar year, using a risk-stacking model. RESULTS: Underlying medical conditions with the highest adjusted RR for IPD were chronic liver disease (RR 2.1, 95% CI 1.5-2.8) and chronic obstructive pulmonary disease (COPD; RR 2.1, 95% CI 1.8-2.5). IPD risk increased with increasing number of medical conditions: adjusted RR, 2.2 (95% CI 1.9-2.5) 1 condition, 2.9 (2.5-3.5) for 2 conditions, and 5.2 (4.4-6.1) for 3 conditions. CONCLUSIONS: For persons with a single, non-IC medical condition, IPD risk was twice that for the general KPNC population. Persons with multiple, non-IC chronic conditions exhibited increased IPD risk with each additional condition. Such information may inform discussions on recommendations for adult pneumococcal immunization and prevention. PMID- 27396494 TI - Stability of the Frank-Kasper sigma-phase in BABC linear tetrablock terpolymers. AB - The phase behavior of B1AB2C tetrablock terpolymer melts is systematically studied using the self-consistent field theory, focusing on the emergence and stability of the complex Frank-Kasper sigma-phase. Our study starts with an investigation of the stability region of the sigma phase for a generic model of B1AB2C terpolymers, in which the C-blocks form spherical domains immersed in the A/B matrix. Then, we examine the stability of the sigma phase for a model system with a specific set of parameters mimicking poly(styrene-b-isoprene-b-styrene-b ethylene oxide) (SISO) block copolymers which were examined in recent experiments. Our results reveal that the formation of the sigma phase is mainly governed by two factors. The first factor is the conformational asymmetry between the A/B-blocks and the C-block, similar to that in conformationally asymmetric AB type block copolymers. The second factor is the specific chain architecture of B1AB2C. The tetrablock architecture with a specific set of interaction parameters and compositions leads to the formation of large core-shell spherical domains, which amplifies the effect of interfacial energy and thereby stabilizes the sigma phase. PMID- 27396495 TI - Dielectric Analysis for the Spherical and Rodlike Micelle Aggregates Formed from a Gemini Surfactant: Driving Forces of Micellization and Stability of Micelles. AB - The self-aggregation behavior of Gemini surfactant 12-2-12 (ethanediyl-1,2 bis(dimethyldodecylammonium bromide)) in water was investigated by dielectric relaxation spectroscopy (DRS) over a frequency range from 40 Hz to 110 MHz. Dielectric determination shows that well-defined spherical micelles formed when the concentration of the surfactant was above a critical micelle concentration CMC1 of 3 mM and rodlike micelles formed above CMC2, 16 mM. The formation mechanism of the spherical micelles and their transition mechanism to clubbed micelles were proposed by calculating the degree of counterion binding of the micelles. The interactions between the head groups and the hydrophobic chains of the surfactant led to the formation of the micelles, whereas the transition is mainly attributed to the interaction among the hydrophobic chains. By analyzing the dielectric relaxation observed at about 10(7) Hz based on the interface polarization theory, the permittivity and conductivity of micelle aggregates (spherical and clubbed) and volume fraction of micelles were calculated theoretically as well as the electrical properties of the solution medium. Furthermore, we also calculated the electrokinetic parameters of the micelle particle surface, surface conductivity, surface charge density, and zeta potential, using the relaxation parameters and phase parameters. On the basis of these results, the balance of forces controlling morphological transitions, interfacial electrokinetic properties, and the stability of the micelle aggregates was discussed. PMID- 27396496 TI - The alteration of H4-K16ac and H3-K27met influences the differentiation of neural stem cells. AB - The neural stem cell therapy provides a promising future for patients with central nerve system damage, thus an insight into its differentiation mechanism is urgently needed. Herein, we aimed to identify various histone modifications and reveal their impact on the differentiation of neural stem cells (NSCs) toward neurons. Firstly, we labeled primary NSCs using the stable isotope labeling with amino acids in cell culture (SILAC) technique. Then we induced these NSCs to differentiate by all-trans retinoic acid (atRA) or SB216763. Next, we identified the alteration of histone modifications in early-differentiated NSCs by mass spectrometry and verified them by Western blot. Interestingly, these modification alterations and phenotype changes were found similar in NSCs induced by the two different drugs. More interestingly, during the differentiation process H3-K27met was significantly up-regulated while H4-K16ac was not altered at the global level but down-regulated in some low-abundance combinatorial codes. We inhibited the methyltransferase of H3-K27 and deacetylase of H4-K16 simultaneously and found the differentiation procedure was obviously delayed. The function of H4-K16ac and H3-K27met in NSCs differentiation would be useful to reveal the differentiation mechanism and valuable for further neural stem cell therapy. PMID- 27396497 TI - Purification of plant complex protein extracts in non-denaturing conditions by in solution isoelectric focusing. AB - An alternative approach for plant complex protein extracts pre-purification by in solution isoelectric focusing in non-denaturing conditions is presented. The separation of biologically active proteins, in narrow ranges of isoelectric point (pI) was obtained by a modified OFFGEL electrophoresis. Two different water soluble protein extracts from Phragmites leaves were fractionated into 24 fractions within a 3-10 pI range at 10 degrees C in the absence of denaturing/reducing agents. One-dimensional electrophoretic analysis revealed different protein distribution patterns and the effective fractionation of both protein extracts. Peroxidase activity of each fraction confirmed that proteins remained active and pre-purification occurred. Biological triplicates assured the needed reproducibility. PMID- 27396498 TI - Genetics and Other Risk Factors for Past Concussions in Active-Duty Soldiers. AB - Risk factors for concussion in active-duty military service members are poorly understood. The present study examined the association between self-reported concussion history and genetics (apolipoprotein E [APOE], brain-derived neurotrophic factor [BDNF], and D2 dopamine receptor genes [DRD2]), trait personality measures (impulsive-sensation seeking and trait aggression hostility), and current alcohol use. The sample included 458 soldiers who were preparing to deploy for Operation Iraqi Freedom/Operation Enduring Freedom. For those with the BDNF Met/Met genotype, 57.9% (11/19) had a history of one or more prior concussions, compared with 35.6% (154/432) of those with other BDNF genotypes (p = 0.049, odds ratio [OR] = 2.48). APOE and DRD2 genotypes were not associated with risk for past concussions. Those with the BDNF Met/Met genotype also reported greater aggression and hostility personality characteristics. When combined in a predictive model, prior military deployments, being male, and having the BDNF Met/Met genotype were independently associated with increased lifetime history of concussions in active-duty soldiers. Replication in larger independent samples is necessary to have more confidence in both the positive and negative genetic associations reported in this study. PMID- 27396499 TI - Reference ranges for short-term heart rate variability measures in individuals free of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: Normative values for heart rate variability (HRV) measures from 10-s electrocardiograms (ECG) have not been defined. METHODS: We reported borderline abnormal (<5th percentile) and abnormal (<2nd percentile) values of standard deviation of all normal-to-normal R-R intervals (SDNN) and root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) from 10-s ECGs in 1175 participants (mean age=59+/-10; 59% female; 47% white) >=45years of age from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of cardiovascular disease (CVD) and CVD risk factors. We validated the prognostic significance of these measures in a subset of the MESA cohort with complete data. RESULTS: Borderline abnormal and abnormal SDNN and rMSSD varied by sex and race. Borderline abnormal and abnormal SDNN and rMSSD were associated with an increased risk of CVD and all-cause mortality. CONCLUSIONS: The references ranges provided in this report will guide future research using these common HRV parameters. PMID- 27396500 TI - Maternal monocytes in pregnancy and preeclampsia in humans and in rats. AB - Monocytes are short-lived cells, arising from the bone marrow and maturing in the circulation. They play an important role in immune responses and are thought to be important for healthy pregnancy. In humans, 3 subpopulations of monocytes have been identified: classical, intermediate and non-classical monocytes. These subpopulations have different functions and phenotypical characteristics. Healthy pregnancy is characterized by a pro-inflammatory condition, with increased numbers of monocytes and monocyte activation as well as with increased numbers of intermediate monocytes and decreased numbers of classical monocytes. This may suggest monocyte maturation. Preeclampsia is an important pregnancy complication characterized by hypertension and proteinuria developing in the second half of pregnancy. The pathophysiology of preeclampsia is associated with further activation of the inflammatory response, further activation of monocytes and further monocyte maturation. In the present review we focus on the role of monocyte activation and maturation in healthy and preeclamptic pregnancy. PMID- 27396501 TI - Proteomic analysis and immunodetection of antigens from early developmental stages of Trichinella spiralis. AB - Trichinella spiralis is an ubiquitous parasitic nematode that lives in muscle tissue of many hosts and causes trichinellosis in humans. Numerous efforts have been directed at specific detection of this infection and strategies for its control. TSL-1 and other antigens, mainly from muscle larvae (ML), have been used to induce partial protection in rodents. An improvement in protective immunity may be achieved by using antigens from other parasite stages. Further, identification of other parasite antigens may provide insights into their role in the host-parasite interaction. In this study, T. spiralis antigens from early developmental parasite stages, namely ML and pre-adult (PA) obtained at 6h, 18h and 30h post-infection, were identified by proteomic and mass spectrometry analyses. Our findings showed a differential expression of several proteins with molecular weights in the range of 13-224kDa and pI range of 4.54-9.89. Bioinformatic analyses revealed a wide diversity of functions in the identified proteins, which include structural, antioxidant, actin binding, peptidyl prolyl cis-trans isomerase, motor, hydrolase, ATP binding, magnesium and calcium binding, isomerase and translation elongation factor. This, together with the differential recognition of antigens from these parasite stages by antibodies present in intestinal fluid, in supernatants from intestinal explants, and in serum samples from mice infected with T. spiralis or re-infected with this parasite, provides information that may lead to alternatives in the design of vaccines against this parasite or for modulation of immune responses. PMID- 27396502 TI - 5-aza-2'-deoxycytidine impairs mouse spermatogenesis at multiple stages through different usage of DNA methyltransferases. AB - Mammalian spermatogenesis is a progressive process comprising spermatogonial proliferation, spermatocytic meiosis, and later spermiogenesis, which is considered to be under the regulation of epigenetic parameters. To gain insights into the significance of DNA methylation in early spermatogenesis, 5-azadC was used as a molecular biological tool to mimic the level of DNA methylation in vivo. Since the drug is incorporated into DNA during the S-phase, spermatogonia and spermatocytes would be affected primarily in mouse spermatogenesis. Adult male ICR mice were intraperitoneally injected with 5-azadC at a dose of 0.25mg/kg/day for 10 consecutive days, allowing us to examine its maximum effect on the kinetics of spermatogonia and spermatocytes. In this short-term protocol, 5-azadC induced significant histological abnormalities, such as a marked increase in apoptosis of spermatogonia and spermatocytes, followed by severe loss of spermatids, while after termination of 5-azadC treatment, normal histology was restored in the testis within 35days. Quantification of the methylation level of CCGG sites as well as whole DNA showed spermatogonial hypomethylation, which correlated with increased apoptosis of spermatogonia. Interestingly, the hypomethylated cells were simultaneously positive for tri-methylated histone H3 at K4. On the other hand, no changes in methylation level were found in spermatocytes, but PCNA staining clearly showed disordered accumulation of S phase spermatocytes, which increased their apoptosis in stage XII. In addition, different immunohistochemical staining pattern was found for DNA methyltransferases (DNMTs); DNMT1was expressed in the majority of all germ cells, but DNMT3a and b were only expressed in spermatogonia. Our results indicate that 5-azadC caused DNA hypomethylation in spermatogonia, but induced prolongation of S-phase in spermatocytes, resulting in the induction of apoptosis in both cases. Thus, 5-azadC affects spermatogenesis at more than one differentiation stage with different mechanisms, probably due to the specific usage of DNMTs. PMID- 27396503 TI - [Second victim management in Galicia]. PMID- 27396504 TI - Corrigendum to "Synthesis of novel anticancer ruthenium-arene pyridinylmethylene scaffolds via three-component reaction" [Bioorg. Med. Chem. Lett. 26 (2016) 2695 2700]. PMID- 27396505 TI - Design and synthesis of new homo and hetero bis-piperazinyl-1-propanone derivatives as 5-HT7R selective ligands over 5-HT1AR. AB - In this work we report the discovery of new homo and hetero bis-piperazinyl-1 propanone derivatives as selective ligands for 5-HT7 over 5-HT1A receptor. These newly synthesized compounds possess a 4-arylpiperazine linked through an acyl spacer to another substituted piperazine system and were tested for their binding properties on human cloned 5-HT1A and 5-HT7 serotonin receptors. Among these, phenyl, 4- and 2-chlorophenyl, 2-methoxyphenyl, 2-pyridyl, and 2-pyrimidyl derivatives 15, 24, 25, and 27-29 displayed nanomolar affinity values for the 5 HT7 receptor (Ki 23.5-52.0nM) and no affinity for the 5-HT1A receptor. PMID- 27396506 TI - Automated circuit fabrication and direct characterization of carbon nanotube vibrations. AB - Since their discovery, carbon nanotubes have fascinated many researchers due to their unprecedented properties. However, a major drawback in utilizing carbon nanotubes for practical applications is the difficulty in positioning or growing them at specific locations. Here we present a simple, rapid, non-invasive and scalable technique that enables optical imaging of carbon nanotubes. The carbon nanotube scaffold serves as a seed for nucleation and growth of small size, optically visible nanocrystals. After imaging the molecules can be removed completely, leaving the surface intact, and thus the carbon nanotube electrical and mechanical properties are preserved. The successful and robust optical imaging allowed us to develop a dedicated image processing algorithm through which we are able to demonstrate a fully automated circuit design resulting in field effect transistors and inverters. Moreover, we demonstrate that this imaging method allows not only to locate carbon nanotubes but also, as in the case of suspended ones, to study their dynamic mechanical motion. PMID- 27396507 TI - Use of electronic health records by child primary healthcare providers in Europe. AB - BACKGROUND: There is limited data on the use and functionality level of electronic health records (EHRs) supporting primary child health care in Europe. Our objective was to determine European primary child healthcare providers' use of EHRs, and functionality level of the systems used. METHODS: European primary care paediatricians, paediatric subspecialists and family doctors were invited by European Academy of Paediatrics Research in Ambulatory Setting Network (EAPRASnet) country coordinators to complete a web-based survey on the use of EHRs and the systems' functionalities. Binomial logistic analysis has been used to evaluate the effect of specialty and type of practice on the use of EHRs. RESULTS: The survey was completed by 679 child primary healthcare providers (response rate 53%). Five hundred and fifty four responses coming from 10 predominant countries were taken for further analysis. EHR use by respondents varied widely between countries, all electronic type use ranging between 7% and 97%. There was no significant difference in EHR use between group practice and solo practitioners, or between family doctors and primary care paediatricians. History and physical examination can be properly recorded by respondents in most countries. However, growth chart plotting capacity in some countries ranges between 22% and 50%. Vaccination recording capacity varies between 50% and 100%, and data exchange capacity with immunization databases is mostly limited, ranging between 0% and 54%. CONCLUSIONS: There is marked heterogeneity in the use and functionalities of EHRs used among child primary child healthcare providers in Europe. More importantly, lack of critical paediatric supportive functionalities like growth tracking and vaccination status has been documented in some countries. There is a need to explore the reasons for these findings, and to develop a cross European paediatric EHR standards. PMID- 27396508 TI - Exposure to high-fat diet since post-weaning induces cardiometabolic damage in adult rats. AB - AIMS: This study sought to investigate the metabolic, hemodynamic and autonomic responses in adult rats exposed to high-fat diet since post-weaning. MAIN METHODS: Young male Wistar rats were assigned into groups fed with standard normal diet (3% lipids; ND, n=8) or high-fat diet (30% lipids; HD, n=8) during 8weeks. Body composition, food intake, serum triglycerides, total cholesterol, insulin, leptin and adiponectin concentrations were determined. Hemodynamic and autonomic evaluations were performed. Renin angiotensin system and nitric oxide were also studied by pharmacological blockades. KEY FINDINGS: HD group showed no difference in body weight, total cholesterol, food intake in calories and insulin concentration, but visceral fat pads weight, triglycerides and leptin were higher in HD group. Moreover, HD group decreased adiponectin level, increased 12% of mean arterial pressure (MAP) and 6% of heart rate compared with ND group. Spectral analyses showed an increase in cardiovascular sympathetic modulation in HD compared with ND group. Depressor responses after losartan were higher in HD compared with ND group: -9+/-0.7 vs.-3+/-1.6mmHg. Pressor responses after l-NAME were higher in HD compared with ND: 45+/-8 vs. 32+/-5mmHg. SIGNIFICANCE: High-fat diet consumption during early period of life can increase WAT mass and MAP. These alterations may be mediated by an augment in sympathetic activity associated with higher leptin and lower adiponectin levels. These cardiometabolic damages can lead to the development of hypertension and increase cardiovascular risk in adulthood. PMID- 27396509 TI - [Arterial dissection: Different entities for the same name]. AB - Spontaneous arterial dissection is a disease whose prevalence is difficult to know and which varies according to the affected artery territory. It can affect the aorta and all medium caliber peripheral arteries including cerebrovascular arteries, coronary arteries and renal arteries. The pathophysiology is common, it is a bleeding in the media. The causes are diverse and vary by territory. Affected patients have few cardiovascular risk factors. Fibromuscular dysplasia is the condition to look for in these few presentations. The vital and functional prognosis may be engaged. Treatment varies depending on territory, severity, and etiology. Conservative treatment is the first-line treatment. PMID- 27396510 TI - Corticosteroid Therapy for a Patient with Relapsing Polychondritis Complicated by IgG4-Related Disease. AB - Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4 RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown. PMID- 27396511 TI - Elevated Urinary Levels of 8-Hydroxy-2'-deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome. AB - Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2' deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders. PMID- 27396512 TI - Aging and Rejuvenation: Insights from Rusty Gage, Leonard Guarente, and Amy Wagers. PMID- 27396513 TI - Our Mothers' Antibodies as Guardians of our Commensals. AB - Mucosal secretory IgA protects the mammalian body from invasion of commensal bacteria colonizing the intestine. A recent murine study in Cell shows that commensal-specific antibodies of the IgG isotype are also present in the serum and that maternal commensal-specific IgA and IgG are crucial for maintaining host microbe mutualism in the offspring. PMID- 27396514 TI - Dry eye disease in an adult population in South-West Nigeria. AB - AIM: To determine the prevalence and factors associated with dry eye disease (DED) in an adult population in south-west Nigeria. METHOD: A descriptive cross sectional community-based study was conducted among respondents aged 40 years and above. Questionnaires were administered on symptoms of DED, followed by ocular examination to elicit signs of DED by determining the tear film break-up time, corneal fluorescein staining score, and Schirmer I tests. Dry eye was diagnosed by the simultaneous presence of at least one symptom experienced "often or all of the time" and at least one sign in either eye. RESULT: The respondents (n=363; females 188) were aged 59.1+/-13.1years. The prevalence of DED was 32.5% (95% CI=27.7-37.3), and the most commonly reported symptoms were grittiness (53.4%, 95% CI=44.4-62.4) and burning/stinging sensation (48.3%, 95% CI=39.3-57.3). On multivariate analysis, DED was significantly associated with age (OR 2.89, 95% C.I=1.67-4.93, p<0.001) but not use of benzalkonium containing topical medications, previous ocular surgery, household fuel use, menopausal status and presence of pterygium. CONCLUSION: The outcome of the study shows that the prevalence of DED among adults above 40 years in south-west Nigeria is 32.5% and the associated risks include older age. PMID- 27396515 TI - Human infection by acanthocephalan parasites belonging to the genus Corynosoma found from small bowel endoscopy. AB - A 73-year-old man with a suspected ileus in January 2013 and subsequently suffered melena in February 2014 was endoscopically examined. As a result of the examinations, unidentified species of Corynosoma sp. and Corynosoma villosum were recovered from the small intestine, further endoscopic diagnosis suggested relevance between abdominal pain and the present infections in the small intestine. The recovered worms were composed of gravid females with developed eggs, suggesting that these parasites can survive for a long time in the intestine after infection. In this case, the short interval between infections appears to be due to the individual's eating habits which consist of regularly consuming uncooked seafood. PMID- 27396516 TI - Differential weakness of finger extensor muscles: A clinical pattern of multifocal motor neuropathy. AB - INTRODUCTION: Several studies have suggested that differential weakness in muscles supplied by the same motor nerve supports the diagnosis of multifocal motor neuropathy (MMN). METHODS: We describe the clinical, electrophysiological, neuroimaging, and laboratory findings of patients with a lower motor syndrome whose clinical presentation included differential finger extension weakness that we have seen in our neuromuscular clinic. RESULTS: We identified 3 patients with hand weakness and 1 patient with asymmetric weakness of the upper extremity. Conduction blocks (CBs) were identified in 1 patient. Anti-GM1 immunoglobulin M antibodies were detected in 2 of the 3 patients tested. Only 1 patient responded to intravenous immunoglobulin (IVIg). Rituximab was administered in another patient, but we did not detect a response. CONCLUSIONS: We suggest that differential finger extension weakness is a feature that may be seen in MMN, even in the absence of CB or response to IVIg. Muscle Nerve 55: 433-437, 2017. PMID- 27396517 TI - Contribution of polio eradication initiative to effective new vaccine introduction in Africa, 2010-2015. AB - BACKGROUND: Significant progress has been made to increase access to vaccines in Africa since the 1974 launch of the Expanded Programme on Immunization (EPI). Successes include the introduction of several new vaccines across the continent and likely eradication of polio. We examined the contribution of polio eradication activities (PEI) on new vaccine introduction in the countries of the African Region. METHODS: We reviewed country specific PEI reports to identify best practices relevant to new vaccine introduction (NVI), and analyzed trends in vaccine coverage during 2010-2015 from immunization estimates provided by WHO/UNICEF. RESULTS: Of the 47 countries in African Region 35 (74%) have introduced PCV, 27 (57%) have introduced rotavirus, and 14 (30%) have introduced IPV. National introductions for HPV vaccine have been done in 5 countries, while 15 countries have held demonstration and pilot projects. In 2014, the regional coverage for the third dose of PCV (PCV3) and rotavirus vaccines was 50% and 30% respectively. By end of 2015, all countries within the meningitis belt will have introduced MenAfriVacTM vaccine. CONCLUSIONS: PEI activities had a positive effect in strengthening the process of new vaccine introduction in the African Region. The major contribution was in availing immunization funding and providing trained and experienced technical staff to introduce vaccines. More investment is needed to advocate and sustain funding levels to maintain the momentum gained in introducing new vaccines in the region. PMID- 27396518 TI - Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia. AB - BACKGROUND: More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia. METHODS: Infants born in Melbourne were randomly allocated to immunisation with BCG-Denmark at birth or two months of age. Ten weeks after immunisation, anti-mycobacterial immune responses were measured in a whole blood assay using intracellular cytokine assays and xMAP multiplex cytokine analysis. RESULTS: Result from 98 BCG immunised infants were included in the final analysis. BCG immunisation at birth (n=54) and at 2months of age (n=44) induced comparable proportions of mycobacteria-specific cytokine-producing CD4 and CD8 T cells, as well as comparable proportions of polyfunctional (TNF(+) IL-2(+) IFN-gamma(+)) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups. CONCLUSIONS: Cellular immunity measured 10weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2months of age. Although definitive correlates of protection against TB remain uncertain, these results suggest that delaying BCG immunisation does not confer any immunological advantage in cellular immunity. PMID- 27396519 TI - Falling in the elderly; a clarification of results. PMID- 27396520 TI - The secret of the questions: medical interview in 21st century. PMID- 27396521 TI - Current status and biotechnological advances in genetic engineering of ornamental plants. AB - Cut flower markets are developing in many countries as the international demand for cut flowers is rapidly growing. Developing new varieties with modified characteristics is an important aim in floriculture. Production of transgenic ornamental plants can shorten the time required in the conventional breeding of a cultivar. Biotechnology tools in combination with conventional breeding methods have been used by cut flower breeders to change flower color, plant architecture, post-harvest traits, and disease resistance. In this review, we describe advances in genetic engineering that have led to the development of new cut flower varieties. PMID- 27396522 TI - Biological nitrate removal from water and wastewater by solid-phase denitrification process. AB - Nitrate pollution in receiving waters has become a serious issue worldwide. Solid phase denitrification process is an emerging technology, which has received increasing attention in recent years. It uses biodegradable polymers as both the carbon source and biofilm carrier for denitrifying microorganisms. A vast array of natural and synthetic biopolymers, including woodchips, sawdust, straw, cotton, maize cobs, seaweed, bark, polyhydroxyalkanoate (PHA), polycaprolactone (PCL), polybutylene succinate (PBS) and polylactic acid (PLA), have been widely used for denitrification due to their good performance, low cost and large available quantities. This paper presents an overview on the application of solid phase denitrification in nitrate removal from drinking water, groundwater, aquaculture wastewater, the secondary effluent and wastewater with low C/N ratio. The types of solid carbon source, the influencing factors, the microbial community of biofilm attached on the biodegradable carriers, the potential adverse effect, and the cost of denitrification process are introduced and evaluated. Woodchips and polycaprolactone are the popular and competitive natural plant-like and synthetic biodegradable polymers used for denitrification, respectively. Most of the denitrifiers reported in solid-phase denitrification affiliated to the family Comamonadaceae in the class Betaproteobacteria. The members of genera Diaphorobacter, Acidovorax and Simplicispira were mostly reported. In future study, more attention should be paid to the simultaneous removal of nitrate and toxic organic contaminants such as pesticide and PPCPs by solid-phase denitrification, to the elucidation of the metabolic and regulatory relationship between decomposition of solid carbon source and denitrification, and to the post-treatment of the municipal secondary effluent. Solid-phase denitrification process is a promising technology for the removal of nitrate from water and wastewater. PMID- 27396523 TI - Low-cost and eco-friendly green synthesis of silver nanoparticles using Prunus japonica (Rosaceae) leaf extract and their antibacterial, antioxidant properties. AB - Low cost and eco-friendly green synthesis of silver nanoparticles (AgNPs) from silver nitrate (AgNO3) using Prunus japonica leaves extract as reducing agent by a simple method at room temperature. The biosynthesized nanoparticles (NPs) were characterized by UV-Vis, tunneling electron microscopy (HR-TEM), scanning electron microscopy (SEM) coupled with X-ray energy dispersive spectrophotometer (EDAX), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). In UV-Vis spectroscopy results, the lambdamax was observed at 441 nm. The AgNPs synthesized were spherical, hexagonal, and irregular in shapes. The EDAX and XRD spectrum confirmed the presence of silver ions and crystalline nature of synthesized AgNPs. FTIR showed the functional groups such as C = O, N-H and C-N groups involved in the reduction of Ag+ to Ag. 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was performed and it showed the percentage inhibition in concentration-dependent manner. The synthesized AgNPs showed antibacterial activity against Escherichia coli, Proteus vulgaris, Staphylococcus aureus and Bacillus cereus to different extents and the higher activity was observed in Proteus vulgaris. PMID- 27396524 TI - Monitoring speed before and during a speed publicity campaign. AB - Driving speeds were monitored during a period of 16 weeks encompassing different stages of an anti-speeding campaign in the Netherlands. This campaign targeted speed limit violations in built-up areas. The observation periods differed in terms of intensity and media used for the campaign. Small road-side radars, mounted in light poles, were used and registered the speeds on 20 locations in built-up areas. Speeds of over 10 million vehicles were measured. Ten locations had a posted speed limit of 50km/h; the other ten had a posted speed limit of 30km/h. Posters were placed at half of each group of locations to remind drivers of the speed limit. The average speed on the 50km/h roads was 46.2km/h, and 36.1km/h on the 30km/h roads. The average proportions of vehicles exceeding the speed limit were 33.3% and 70.1% respectively. For the 30km/h roads, the data shows differences in speed and speeding behaviour between the six distinguished observation periods, but overall these differences cannot be logically linked to the contents of the phases and, hence, cannot be explained as an effect of the campaign. The only exception was an effect of local speed limit reminders on the 30km/h roads. This effect, however, was temporary and had disappeared within a week. PMID- 27396525 TI - The critical role of epigenetics in systemic lupus erythematosus and autoimmunity. AB - One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary cirrhosis will also be summarized. Importantly we emphasize that the stochastic processes that lead to DNA modification may be the lynch pins that drive the initial break in tolerance. PMID- 27396527 TI - Erratum to "Non-resurfacing techniques in the management of the patella at total knee arthroplasty: A systematic review and meta-analysis" [The Knee 23 (2016) 191 197]. PMID- 27396526 TI - Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity. AB - GM-CSF is a cytokine produced by T helper (Th) cells that plays an essential role in orchestrating neuroinflammation in experimental autoimmune encephalomyelitis, a rodent model of multiple sclerosis. Yet where and how Th cells acquire GM-CSF expression is unknown. In this study we identify mast cells in the meninges, tripartite tissues surrounding the brain and spinal cord, as important contributors to antigen-specific Th cell accumulation and GM-CSF expression. In the absence of mast cells, Th cells do not accumulate in the meninges nor produce GM-CSF. Mast cell-T cell co-culture experiments and selective mast cell reconstitution of the meninges of mast cell-deficient mice reveal that resident meningeal mast cells are an early source of caspase-1-dependent IL-1beta that licenses Th cells to produce GM-CSF and become encephalitogenic. We also provide evidence of mast cell-T cell co-localization in the meninges and CNS of recently diagnosed acute MS patients indicating similar interactions may occur in human demyelinating disease. PMID- 27396528 TI - Clinical analysis of bronchoscopic cryotherapy in 156 pediatric patients. AB - BACKGROUND: The aim of this study was to investigate the efficacy and safety of bronchoscopic cryotherapy for pediatric poor ventilation. METHODS: A total of 156 pediatric patients with airway stenosis and obstruction as well as pulmonary atelectasis received bronchoscopic cryotherapy. Treatment efficacy was evaluated on bronchoscopy Before cryotherapy and after the last cryotherapy treatment. Pulmonary atelectasis was assessed according to range of atelectasis on chest computed tomography (CT), and tracheobronchial stenosis according to pulmonary function, tidal volume analysis and dyspnea index. RESULTS: The 154 patients with effective treatment had patent airway, smooth mucosa and resolved atelectasis. In the two patients with ineffective treatment, however, the airway was not smooth and the range of pulmonary atelectasis was reduced by <30%. Among the 156 patients, 136 had markedly effective treatment, with CT pulmonary atelectasis recovery >70%. The width of the main airway significantly increased approximately 50% and the tidal volume or capacity increased 100%. Effective treatment was identified in 18 patients (18/156), with CT pulmonary atelectasis area reduced 30 70%. Ineffective treatment was noted in two patients, with CT pulmonary atelectasis area reduced by <30%. No complications were noted in any patients during or after operation. No recurrence was noted on follow up of 2-24 months. CONCLUSION: Bronchoscopic cryotherapy is effective and safe for dyspnea caused by airway obstruction, and wide application in clinic is recommended. PMID- 27396529 TI - Notalgia Paresthetica and Multiple Endocrine Neoplasia Syndrome 2A: A Case Report. AB - Notalgia paresthetica is characterized by a hyperpigmented macular pruritic skin lesion most commonly localized unilaterally in the middle and upper back region. This condition has been reported in association with multiple endocrine neoplasia syndrome type 2A (MEN 2A) in several families; it rarely affects children and it may serve as an early marker of MEN 2A. We report a 9-year-old girl diagnosed with MEN 2A and notalgia paresthetica. PMID- 27396531 TI - Lipid mediators as regulators of human ILC2 function in allergic diseases. AB - Group 2 innate lymphoid cells (ILC2) are specialized in type 2 immunity. ILC2 are activated early in immune responses and, despite their low abundance, are able to initiate and amplify allergic inflammation by orchestrating other type 2 immune cells. Based on recent discoveries, the spectrum of ILC2 regulating factors has been extended. It is now well established that not only epithelial cell-derived innate cytokines, but also bioactive lipids can regulate ILC2 activity and accumulation. Additionally, ILC2 appear to be susceptible to changes in the cytokine milieu and can acquire an ILC1-like phenotype due to a high degree of cellular plasticity. As ILC2 are fundamentally involved in the pathogenesis of type 2 diseases, they represent a promising therapeutic target for allergic airway and skin diseases. In this review we summarize the current knowledge about ILC2 biology in the allergy context, with a particular focus on the emerging role of lipid mediators in regulating ILC2 function. PMID- 27396530 TI - Seasonal Variations of Nutritional Status in Maintenance Hemodialysis Patients. AB - Nutritional status of hemodialysis (HD) patients is influenced by a multitude of factors and it strongly correlates with morbidity and mortality. The aim of this study was to investigate the influence of seasonal changes on nutritional status in maintenance HD patients. A selected population of 84 adult (40 females and 44 males, aged 68.98 +/- 13.45 years) HD (5.94 +/- 6.44 years) patients were investigated. Clinical, biochemical and nutritional parameters (BMI, creatinine, urea, serum albumin, total cholesterol and Dialysis Malnutrition Score (DMS) were measured in cold (January and December) and mild (June and September) months, altogether in 336 HD sessions. Statistically significant differences between cold and mild months were found in BMI (P = 0.046), creatinine before HD (P = 0.011), urea before HD (P <= 0.001), urea after HD (P <= 0.001) and glucose (P = 0.001). Differences between male and female patients in DMS, serum albumin and creatinine level in cold and mild months were found; where females altogether had higher DMS score and lower serum albumin and creatinine levels. These results suggest that seasonal variations of clinical and laboratory variables that reflect nutritional status occur commonly among maintenance HD patients and might lead to biases in the interpretation of results in clinical studies in which measurement schedules vary during the year. Also, results suggested that female HD patients may constitute an especially vulnerable population for seasonal oscillations of nutritional status. The reasons for most of these variations are not apparent and require further investigation. PMID- 27396532 TI - Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells. AB - Indirubin, an active ingredient of a traditional Chinese medicine prescription named Danggui Longhui Wan, has been reported to exhibit abroad anti-cancer and anti-inflammation activities. However, the effect of indirubin on ulcerative colitis (UC) has not been addressed. Here, we investigated the therapeutic efficacy of indirubin on dextran sulfate sodium (DSS)-induced UC in mice and explored its underlying mechanisms. UC model was induced in BALB/c mice by administrating with 3% DSS in drinking water for 7days. Subsequently, indirubin treatment (10mg/kg) for 7days obviously inhibited the loss of body weight, reversed the elevation of disease activity index (DAI), alleviated crypt distortion and mucosal injury, and reduced inflammatory cell infiltration in the colon mucosa, thereby ameliorating DSS-induced UC. Mechanically, the levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-2 as well as myeloperoxidase (MPO) activity in colon tissues were decreased significantly, while the levels of IL-4 and IL-10 were increased remarkably by indirubin treatment. Moreover, indirubin administration effectively suppressed CD4(+) T cell infiltration in the colon of DSS-induced UC mice and promoted the generation of Foxp3-expressing regulatory T cells. Additionally, further studies showed that indirubin obviously inhibited DSS-induced activation of nuclear factor (NF)-kappaB signaling. These results reveal that the significant anti-UC effect of indirubin may be attributable to its inhibition of inflammatory responses and promotion of Foxp3(+) T cells. Our studies provide the first evidence for the anti-UC effect of indirubin as well as the related molecular mechanisms and suggest a promising candidate drug for UC therapy. PMID- 27396533 TI - Six health care trends that will reshape the patient-provider dynamic. AB - Six trends - movement towards value-based payment, rapid adoption of digital health technology, care delivery in non-traditional settings, development of individualized clinical guidelines, increased transparency, and growing cultural awareness about the harms of medical overuse - are driving the US health care system towards a future defined by quality- and patient-centric care. Health care organizations are responding to these changes by implementing provider and workforce changes, pursuing stronger payer-provider integration, and accelerating the use of digital technology and data. While these efforts can also improve the clinical relationship and create positive system redesign among health care organizations, they require alignment between organizational and physician incentives that can inadvertently harm the dynamic between patients and providers. Organizations can utilize several strategies to preserve the patient physician relationship and advance the positive benefits of new organizational strategies while guarding against unintended consequences. PMID- 27396534 TI - "A Bayesian sensitivity analysis to evaluate the impact of unmeasured confounding with external data: a real world comparative effectiveness study in osteoporosis". AB - PURPOSE: Observational studies are frequently used to assess the effectiveness of medical interventions in routine clinical practice. However, the use of observational data for comparative effectiveness is challenged by selection bias and the potential of unmeasured confounding. This is especially problematic for analyses using a health care administrative database, in which key clinical measures are often not available. This paper provides an approach to conducting a sensitivity analyses to investigate the impact of unmeasured confounding in observational studies. METHODS: In a real world osteoporosis comparative effectiveness study, the bone mineral density (BMD) score, an important predictor of fracture risk and a factor in the selection of osteoporosis treatments, is unavailable in the data base and lack of baseline BMD could potentially lead to significant selection bias. We implemented Bayesian twin-regression models, which simultaneously model both the observed outcome and the unobserved unmeasured confounder, using information from external sources. A sensitivity analysis was also conducted to assess the robustness of our conclusions to changes in such external data. RESULTS: The use of Bayesian modeling in this study suggests that the lack of baseline BMD did have a strong impact on the analysis, reversing the direction of the estimated effect (odds ratio of fracture incidence at 24 months: 0.40 vs. 1.36, with/without adjusting for unmeasured baseline BMD). CONCLUSIONS: The Bayesian twin-regression models provide a flexible sensitivity analysis tool to quantitatively assess the impact of unmeasured confounding in observational studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27396535 TI - Fulminant hepatic failure requiring liver transplantation due to accidental alcohol ingestion in a 7-month-old baby. PMID- 27396536 TI - Amino-terminal pro-B-type natriuretic peptide, inferior vena cava ultrasound, and biolectrical impedance analysis for the diagnosis of acute decompensated CHF. AB - BACKGROUND: Both Framingham criteria and natriuretic peptides (NPs) may worsen their diagnostic validity for acute decompensated heart failure (ADHF) in elderly patients with comorbidities, mainly renal failure. Ultrasound of inferior vena cava (IVCu) and bioelectrical impedance analysis (BIA) are useful tools for detecting ADHF, although their utility compared with NP is not fully established. METHODS AND RESULTS: We conducted a prospective study with 96 patients who presented at the emergency department with dyspnea and were classified as ADHF and non-ADHF groups. Inferior vena cava ultrasonography measured maximum and minimum inferior vena cava diameters and collapsibility index (CIx), whereas BIA calculated resistance (Rz) and reactance (Xc). The primary goal was to compare amino-terminal pro-B-type NP (NT-proBNP), IVCu, and BIA for identifying ADHF. The ADHF group showed significantly (P<.001) higher NT-proBNP values (5801 vs 599 pg/mL), higher maximum IVC diameter (2.26 vs 1.58 cm), higher minimum IVC diameter (1.67 vs 0,7 cm), and lower CIx (27% vs 59%), as well as lower Rz (458.8 vs 627.1 Ohm) and lower Xc (23.5 vs 38.4 Ohm) compared with the non-ADHF group. The estimated area under the curve for ADHF diagnosis was 0.84 for NT-proBNP, 0.90 for maximum IVC diameter, 0.93 for minimum IVC diameter, and 0.90 for CIx, as well as 0.83 and 0.80 for Rz and Xc respectively, without finding significant difference. Cutoff values for diagnosis of ADHF with IVCu and BIA are proposed. Amino-terminal pro-B-type NP values significantly varied in patients with renal impairment, independently of ADHF status, whereas neither IVCu nor BIA did. CONCLUSIONS: Inferior vena cava ultrasonography and BIA analysis are as useful as NT-proBNP to ADHF diagnosis, validated in an elderly population with kidney disease. PMID- 27396537 TI - The role of ultrasonography in the diagnosis of metacarpal fractures. AB - INTRODUCTION: The aim of this study was to evaluate the efficiency of ultrasonography (USG) in identifying metacarpal bone fractures in patients admitted to the emergency department (ED) with hand injury. MATERIALS AND METHODS: Patients who were admitted to a training and research hospital's ED during the study period with hand trauma and had suspected metacarpal fractures were included in the study. They were examined for metacarpal fracture by USG and x-ray. Hand radiographs reviewed by an emergency physician were considered to be the criterion standard diagnostic tool. Ultrasonography results were compared to x-ray results. RESULTS: Ninety-eight ultrasound examinations were performed on 96 adult patients who were enrolled in the study. The mean age of the patients was 30.1+/-11.8 years; 79.2% of the patients were male. Right hand injury was observed in 69.4% of the cases. Forty metacarpal fractures were detected in 38 patients on x-ray. We found a sensitivity of 92.5% (95% confidence interval [CI], 78.5-98), a specificity of 98.28% (95% CI, 89.5-99.9), a positive predictive value of 97.37% (95% CI, 84.5-99.8), and a negative predictive value of 95% (95% CI, 85-98) for USG to detect metacarpal fractures when compared to x-ray imaging. CONCLUSIONS: Under the light of these results, we suggest that USG may be an option for detecting metacarpal fractures and prevent unnecessary x-ray imaging examinations in patients presenting to the ED with hand trauma. PMID- 27396538 TI - Diagnostic performance of smartphone reading of the coronary CT angiography in patients with acute chest pain at ED. AB - PURPOSE: The aims of this study were to simulate mobile consultation for the coronary computed tomography angiography (CCTA) at the emergency department (ED) and to measure the diagnostic performance of the mobile reading. MATERIALS AND METHODS: A total of 107 patients with acute chest pain who underwent CCTA and coronary angiography (CAG) were included. The CCTA images were reviewed by a cardiac radiologist using a smartphone. The degree of stenosis at each coronary segment was scored with 4-point scale (score 1, <50%; score 2, 51%-70%; score 3, 71%-90%; score 4, >90%). The degree of stenosis at each coronary segments were also scored with preliminary CCTA report by on-call residents, final CCTA reports by in-house attending cardiac radiologists, and CAG. Interobserver agreement was measured using kappa statistics. The areas under the receiver operating characteristic curves (AUCs) for diagnosing segments with obstructive stenosis were compared between each reader and CAG. RESULTS: The smartphone reader's reading was more similar to the CAG results and in-house radiologists' reports than reading of on-call residents. The diagnostic performance of smartphone reading for detection of obstructive stenosis was significantly greater than that of on-call residents (AUC, 0.89 vs 0.75; P<.001) and did not significantly differ from that of the in-house radiologists (AUC, 0.89 vs 0.90; P=.05). CONCLUSION: Smartphone reading by the cardiac radiologist was superior to the on-call residents' reading. Further study with real-time mobile consultation needs to be investigated to evaluate whether improvement in diagnostic competency can make a difference in the outcome of patients. PMID- 27396539 TI - Cutaneous gangrene of the arms and legs after cardiopulmonary resuscitation: A rare presentation of catastrophic antiphospholipid syndrome. PMID- 27396540 TI - A case of spontaneous coronary artery dissection with ST elevation in aVR and posterior leads. PMID- 27396541 TI - Bacterial vaginosis: a critical analysis of current knowledge. AB - : Bacterial vaginosis (BV), the change from a Lactobacillus-dominant vaginal microbiota to an anaerobic and facultative bacterial dominance, is associated with pathological sequelae. In many BV-positive women their microbiota is in fact normal and unrelated to pathology. Whether or not the dominance of BV-associated bacteria persists depends upon interactions between host and bacterial factors. Inconsistencies in diagnosis and erroneous associations with pathology may be due to a failure to differentiate between sub-populations of women. It is only in those women with a BV diagnosis in which the identified bacteria are atypical and persist that BV may be a clinical problem requiring intervention. TWEETABLE ABSTRACT: Improved diagnosis of bacterial vaginosis is needed to accurately determine its role in pathology. PMID- 27396542 TI - Autoenhanced Raman Spectroscopy via Plasmonic Trapping for Molecular Sensing. AB - As a label-free and sensitive biosensor, surface-enhanced Raman spectroscopy (SERS) is a rapidly emerging technique. However, because SERS spectra are obtained in the area of light excitation and the enhancement effect can be varied depending on the position of a substrate, it is important to match the enhanced area with an illuminated spot. Here, in order to overcome such difficulty, we demonstrated a new technique combining SERS with plasmonic trapping. By plasmonic trapping, we can collect gold nanoparticles (GNPs) in the middle of initially fabricated nanobowtie structures where a laser is excited. As a result of trapping GNPs, hot-spots are formed at that area. Because SERS is measured in the area irradiated by a laser, hot-spot can be simultaneously coincided with a detection site for SERS. By using this, we detected Rhodamine 6G to 100 pM. To further verify and improve the reproducibility of our technique, we also calculated the electric field distribution, trapping force and trapping potential. PMID- 27396543 TI - Off-pump surgery for post-myocardial infarction ventricular septal rupture. AB - Post-myocardial infarction ventricular septal rupture (PIVSR) is a complication of acute myocardial infarction with high mortality. We report a new surgical strategy to treat PIVSR. Instead of traditional open surgery, the septal defect was repaired with periventricular closure off pump. PMID- 27396544 TI - Circadian and ultradian patterns of epileptiform discharges differ by seizure onset location during long-term ambulatory intracranial monitoring. AB - OBJECTIVE: Previous studies reporting circadian patterns of epileptiform activity and seizures are limited by (1) short-term recording in an epilepsy monitoring unit (EMU) with altered antiepileptic drugs (AEDs) and sleep, or (2) subjective seizure diary reports. We studied circadian patterns using long-term ambulatory intracranial recordings captured by the NeuroPace RNS System. METHODS: Retrospective study of RNS System trial participants with stable detection parameters over a continuous 84-day period. We analyzed all detections and long device-detected epileptiform events (long episodes) and defined a subset of subjects in whom long episodes represented electrographic seizures (LE-SZ). Spectrum resampling determined the dominant frequency periodicity and cosinor analysis identified significant circadian peaks in detected activity. Chi-square analysis was used to compare subjects grouped by region of seizure onset. RESULTS: In the 134 subjects, detections showed a strongly circadian and uniform pattern irrespective of region of onset that peaked during normal sleep hours. In contrast, long episodes and LE-SZ patterns varied by region. Neocortical regions had a monophasic, nocturnally dominant rhythm, whereas limbic regions showed a more complex pattern and diurnal peak. Rhythms in some individual limbic subjects were best fit by a dual oscillator (circadian + ultradian) model. SIGNIFICANCE: Epileptiform activity has a strong 24 h periodicity with peak nocturnal occurrence. Limbic and neocortical epilepsy show divergent circadian influences. These findings confirm that circadian patterns of epileptiform activity vary by seizure-onset zone, with implications for treatment and safety, including SUDEP. PMID- 27396545 TI - Risk of nephrolithiasis, hyperoxaluria, and calcium oxalate supersaturation increased after Roux-en-Y gastric bypass surgery: a systematic review and meta analysis. AB - BACKGROUND: Earlier publications have shown renal stone complications after bariatric surgery. Multiple reports have also linked metabolic changes that alter the urinary chemistry profiles, especially hyperoxaluria, after bariatric surgery. However, evidence on change of other urine chemistry studies and type of bariatric surgery and risk of stone has been inconclusive so far. OBJECTIVES: To explore the association between bariatric surgery and postoperative urinary chemistry change and risk of stone formation SETTING: A systematic review and meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their dates of inception to January 2016. The inclusion criteria were published studies of association between bariatric surgery and postoperative renal stone formation or urine chemistry profiles. We used random-effects model meta-analysis and calculated the pooled risk of renal stone and difference in 24-hour urine chemistry profiles. RESULTS: Twelve observational studies were included in the meta-analysis. There was significantly higher risk of stone formation after Roux en-Y gastric bypass surgery with pooled relative risk = 1.79 (95% CI: 1.54-2.10). In the analysis of urine chemistry profiles, there was significantly higher calcium oxalate supersaturation, lower citrate, and lower volume postoperatively compared with preoperatively. There was also higher urine oxalate in patients who had bariatric surgery compared with nonsurgery controls. CONCLUSIONS: Roux-en-Y gastric bypass surgery is associated with higher risk of renal stone and increased urine oxalate and calcium oxalate supersaturation. PMID- 27396547 TI - Comment on: "Conversion of sleeve gastrectomy to Roux-en-Y gastric bypass: an audit of 34 patients" and "Weight loss, weight regain, and conversions to Roux-en Y gastric bypass-10-year results of laparoscopic sleeve gastrectomy". PMID- 27396546 TI - Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse. AB - BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia, obesity, cardiopulmonary diseases, and increased mortality. Although successful weight loss improves health in PWS, few treatments cause sustained weight loss in obese patients let alone obese individuals with PWS. OBJECTIVES: The present study uses the Magel2 knockout (KO) mouse, an animal model of PWS, to conduct a preclinical study on the efficacy of sleeve gastrectomy (SG) in PWS. SETTING: Academic research laboratory, United States. METHODS: We performed sham or SG surgeries in 24- to 28-week-old male Magel2 KO and wild-type littermate control mice (WT) who had been maintained on a high-fat diet for 10 weeks. We monitored weight, food intake, and fat and lean mass pre- and postoperatively. Fasting glucose, glucose tolerance, and counter-regulation were measured postoperatively. RESULTS: Magel2 KO animals had similar recovery and mortality rates compared with WT. SG resulted in similar weight loss, specifically loss of fat but not lean mass, in both Magel2 KO and WT mice. SG also resulted in significantly lower fasting glucose levels and a reduction in fat intake in both Magel2 KO and WT mice. We also found that Magel2 KO mice failed to increase their food intake in response to the glucoprivic agent 2-deoxy-D-glucose, suggesting impaired glucose counter-regulation, but this occurred regardless of surgical status. All results were considered significant when P< .05. CONCLUSION: We find in this mouse model of PWS, SG is a well-tolerated, effective strategy for weight and fat loss. PMID- 27396548 TI - Mid-term outcomes of gastric bypass weight loss failure to duodenal switch. AB - BACKGROUND: The Roux-en-Y gastric bypass (RYGB) is a very effective treatment for obesity and its related co-morbidities. However, some patients fail to achieve>50% of their excess weight loss (EWL), and others regain much of the weight that they lost. OBJECTIVE: The purpose of this study was to analyze early outcomes after conversion of RYGB to duodenal switch (DS) in terms of weight loss, change in co-morbidities, and complications. SETTING: This is a retrospective analysis from 1 surgeon at a single private institution. METHODS: We analyzed data from 32 obese patients retrospectively who underwent revision for failed RYGB. Nine patients underwent DS with Roux-en-Y reconstruction (RYDS), and 23 patients underwent single anastomosis DS between October 2012 and December 2015. Regression analyses were performed for all follow-up weight-loss data. RESULTS: The patients experienced mean EWL of 16.2% over an average of 16 years (range: 0-38) with their primary RYGB surgery. Of 32 patients who underwent revision DS, 22 patients are beyond the 1-year postoperative mark (follow-up 81.8%), and 15 patients are beyond the 2-year postoperative mark (follow-up 73.3%). One patient was lost to follow-up. The patients experienced mean EWL of 31.2%, 45.1%, 51%, 54.2%, 56%, and 56.4% at 3, 6, 9, 12, 18, and 24 months, respectively, after their revisional surgery. Mean total weight loss achieved at 12 and 24 months was 27.7% and 29.2%, respectively. There was no statistical significant difference in mean %EWL at 12 months (P = .468) and 24 months (P = .266) between RYDS and single anastomosis DS. CONCLUSION: A laparoscopic revision from RYGB to DS is an effective weight-loss operation with midterm follow-up of 2 years. Though long-term follow-up is warranted to measure recidivism, the initial data seem favorable. PMID- 27396549 TI - Loose and frequent stools and PTH levels are positively correlated post-gastric bypass surgery due to less efficient intestinal calcium absorption. AB - BACKGROUND: After Roux-en-Y gastric bypass, calcium and vitamin D deficiencies are frequently reported. In the presence of adequate vitamin D levels, calcium deficiency is caused by a lower efficacy of the intestinal calcium transport. OBJECTIVE: To investigate whether the use of a simple clinical score quantifying bowel habits (fecal score [FS]) correlates with the degree of secondary hyperparathyroidism that arises to compensate for calcium deficiency postsurgery. SETTING: Large peripheral hospital. METHODS: Seventy-five patients supplemented with calcium and vitamin D were prospectively studied before and 6 and 12 months after Roux-en-Y gastric bypass. FS, calcium (mmol/L), phosphate (mmol/L), magnesium (mmol/L), vitamin D (nmol/L), and parathyroid hormone (PTH; pmol/L) were measured in each patient. RESULTS: Mean body mass index was 44.7+/-5.4 kg/m2 preoperatively and decreased to 34.3+/-5.0 kg/m2 at 6 months and 30.8+/-4.8 kg/m2 at 12 months, corresponding to a total weight loss of 23.2+/-5.9% and 30.9+/-8.3% respectively. There were no significant changes in serum calcium levels. Mean PTH levels rose from 3.5 pmol/L at baseline to 4.1 pmol/L at 6 months (P = .01) and to 4.9 pmol/L at 12 months (P<.001). Nine patients (12%) had increased PTH levels at 6 months, and 14 patients (19%) had increased PTH levels at 12 months. A significant positive correlation between FS and PTH at 12 months was found, which persisted after adjusting for vitamin D levels. CONCLUSION: FS is positively correlated with secondary hyperparathyroidism using vitamin D-adjusted PTH levels as a biochemical marker. The present study in humans confirms the relation reported in animal studies. These results emphasize that managing stool habits are important after bariatric surgery. PMID- 27396551 TI - Reply: Understanding vascular calcification from an evolutionary approach. PMID- 27396550 TI - Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo. AB - Liver kinase B1 (LKB1) and its downstream effector AMP-activated protein kinase (AMPK) play critical roles in polarity establishment by regulating membrane trafficking and energy metabolism. In collagen sandwich-cultured hepatocytes, loss of LKB1 or AMPK impaired apical ABCB11 (Bsep) trafficking and bile canalicular formation. In the present study, we used liver-specific (albumin-Cre) LKB1 knockout mice (LKB1(-/-) ) to investigate the role of LKB1 in the maintenance of functional tight junction (TJ) in vivo. Transmission electron microscopy examination revealed that hepatocyte apical membrane with microvilli substantially extended into the basolateral domain of LKB1(-/-) livers. Immunofluorescence studies revealed that loss of LKB1 led to longer and wider canalicular structures correlating with mislocalization of the junctional protein, cingulin. To test junctional function, we used intravital microscopy to quantify the transport kinetics of 6-carboxyfluorescein diacetate (6-CFDA), which is processed in hepatocytes into its fluorescent derivative 6-carboxyfluorescein (6-CF) and secreted into the canaliculi. In LKB1(-/-) mice, 6-CF remained largely in hepatocytes, canalicular secretion was delayed, and 6-CF appeared in the blood. To test whether 6-CF was transported through permeable TJ, we intravenously injected low molecular weight (3 kDa) dextran in combination with 6 CFDA. In wild-type mice, 3 kDa dextran remained in the vasculature, whereas it rapidly appeared in the abnormal bile canaliculi in LKB1(-/-) mice, confirming that junctional disruption resulted in paracellular exchange between the blood stream and the bile canaliculus. CONCLUSION: LKB1 plays a critical role in regulating the maintenance of TJ and paracellular permeability, which may explain how various drugs, chemicals, and metabolic states that inhibit the LKB1/AMPK pathway result in cholestasis. (Hepatology 2016;64:1317-1329). PMID- 27396552 TI - Editorial Commentary: Resistant hypertension: Pathogenesis and current and future management. PMID- 27396553 TI - Editorial Commentary: Multiple arterial grafting for coronary revascularization: We are not perplexed but choose ignorance. PMID- 27396554 TI - Editorial Commentary: The evolution of autonomy in sports. PMID- 27396555 TI - Bioinformatic Analysis of Genes and MicroRNAs Associated With Atrioventricular Septal Defect in Down Syndrome Patients. AB - Down syndrome (DS) is a common chromosome 21 abnormality disease, leading to various health problems, especially atrioventricular septal defect (AVSD). Genes and microRNAs (miRNAs) associated with AVSD in DS patients still need in-depth study.Gene expression data (GSE34457) of 22 DS patients without congenital heart disease and 7 DS patients with AVSD were downloaded from Gene Expression Omnibus. After screening differentially expressed genes (DEGs) based on limma package in R (criteria: P < 0.05 and |log2 fold change (FC)| > 0.5), pathway and functional enrichment analyses were performed using the online software DAVID (criterion: P < 0.05). The protein-protein interaction (PPI) networks of DEGs were constructed based on the online server STRING (criterion: combined score > 0.4). Next, miRNAs that targeted DEGs were predicted based on Webgestalt (criteria: P < 0.05 and target DEGs >= 2), and miRNA-DEG regulatory networks were visualized through Cytoscape.A total of 179 DEGs were identified. Next, 5 functions and 1 pathway were enriched by up-regulated DEGs, while 4 functions were enriched by down regulated DEGs. Furthermore, miRNA-DEG regulatory networks were constructed. IL1B was the hub-gene of PPI networks, and AUTS2 and KIAA2022 were predicted to be targeted by miR-518a, miR518e, miR-518f, miR-528a, and miR-96.IL1B, IL12RB2, AUTS2, and KIAA2022 might participate in AVSD in DS patients, and AUTS2 and KIAA2022 might be targeted by miR-518a, miR-518e, miR-518f, miR-528a, and miR-96. The identified genes and miRNAs might provide a theoretical basis for understanding AVSD in DS patients. PMID- 27396556 TI - Relation Between Obesity, Metabolic Syndrome, Successful Long-Term Weight Reduction, and Right Ventricular Function. AB - This study sought to examine the relationships between right ventricular (RV) function and geometry, morbid obesity with and without the metabolic syndrome, and the effect of long-term weight loss. Obese (n = 153, BMI 41.2 +/- 8.7 kg/m(2)) and healthy non-obese control subjects (n = 38, BMI 25.5 +/- 3.3 kg/m(2)) of similar age and gender distribution were prospectively studied during the course of a 1-year weight reduction program with echocardiography at baseline and after one year of follow up. Function and geometry of the right heart were evaluated by tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TDI S'), RV myocardial performance index (TEI), RV end diastolic (RVEDD) and end-systolic diameter (RVESD), area of the right atrium (RAA), and systolic pulmonary artery pressure (PAP). Whereas parameters of systolic and diastolic LV function were significantly worse in the obese subjects than those in the non-obese subjects (EF 66 +/- 6 versus 69 +/- 6%, P = 0.004; E/E' 7.4 +/- 2.5 versus 6.3 +/- 2.6, P = 0.010), parameters of RV function (TAPSE 25.6 +/- 4.5 versus 25.1 +/- 3.5 mm, P = 0.528; TDI S' 13.5 +/- 2.9 versus 13.8 +/- 2.9 mm/second, P = 0.553; TEI 0.25 +/- 0.13 versus 0.28 +/- 0.09, P = 0.283) as well as geometry measurements were comparable between the obese and non-obese participants and also in obese subjects with full blown metabolic syndrome. Additionally, successful weight reduction did not alter the RV parameters. Nevertheless, in the few obese subjects with RV dysfunction (n = 7), metabolic syndrome parameters were more pronounced than in obese with normal RV function.Morbid obesity with and without the metabolic syndrome is accompanied by an impaired LV systolic and diastolic function. In contrast, RV function appears to be less affected by obesity independent of the presence of the metabolic syndrome. PMID- 27396557 TI - A Safety and Efficacy Study of Tolvaptan Following Open Heart Surgery in 109 Cases. AB - This study was conducted to evaluate the safety and efficacy of tolvaptan following open heart surgery.We retrospectively reviewed 109 patients who were administered tolvaptan following open heart surgery between August 2011 and July 2014. We divided the patients according to their urine output index (amount of urine output/body surface area) into tertiles as follows: T1 (low responders; n = 36), T2 (intermediate responders; n = 36), and T3 (high responders; n = 37). No fatal adverse events were observed following tolvaptan administration. The factors that showed a significant difference among the 3 groups were body surface area (BSA) and preoperative body weight. Body weight rapidly decreased and a greater increase in the serum sodium level was observed on day 1 in the T3 group than in the other 2 groups. No decrease in blood pressure and no significant differences in the occurrence of atrial fibrillation were observed among the 3 groups during tolvaptan administration.Tolvaptan can be safely and effectively administered to increase the urine output without adversely affecting the cardiovascular system or renal function following open heart surgery. However, careful attention is required regarding the possibility of a rapid increase in the serum sodium level so it is important to monitor changes in serum Na levels. PMID- 27396558 TI - Summary of Clinical Experience of Modified Double Root Translocation in the Management of Complete Transposition of Great Arteries With Left Ventricular Outflow Tract Obstruction. AB - To summarize the therapeutic effects of modified double root translocation (MDRT) in the management of congenital heart disease-transposition of great arteries (TGA) with ventricular septum defect (VSD) and left ventricular outflow tract obstruction (LVOTO). From May 2013 to March 2015, we treated 6 patients (4 males, 2 females, aged from 1 year and 8 months old to 5 years old) with complete transposition of great arteries with left ventricular outflow tract obstruction, SaO2 54 +/- 7.3%; the outflow velocity of the left ventricular or pulmonary valve measured by Doppler was 4.46 +/- 0.15 m/s, and the Nakata index was 217 +/- 32 cm(2)/m(2). We carried out a double root translocation operation on these 6 patients.One patient developed low cardiac output syndrome 4 hours after the operation. Extracorporeal membrane oxygenation (ECMO) was performed, but the patient died of multiple organ failure. The other 5 patients all recovered and were discharged from the hospital. During the 3-month to 2-year follow-up period, these 5 patients all demonstrated NYHA Class I or NYHA Class II LVEF (65 +/- 2.7) %; 4 had mild pulmonary regurgitation, 1 moderate pulmonary regurgitation; 3 no aortic regurgitation, and 2 micro aortic regurgitation, SaO2 99 +/- 0.4%.Modified double root translocation is an effective treatment method in the management of complete transposition of great arteries with left ventricular outflow tract obstruction. PMID- 27396559 TI - Therapeutic Decision-Making for Elderly Patients With Symptomatic Severe Valvular Heart Diseases. AB - The aim of this study was to determine how older age and co-morbidities affect the treatment decision-making and long-term survival in elderly patients with symptomatic severe valvular heart diseases.A total of 181 elderly patients (mean age, 78.4 +/- 3.4 years) hospitalized between January 2003 and June 2012 with symptomatic severe valvular heart diseases were enrolled. Cardiac and geriatric factors associated with treatment decision-making were analyzed. Survival outcomes were investigated.Surgical treatment was performed in 116 (64%) patients (surgical group) and 65 patients (36%) were treated conservatively (conservative group). The most common [62% (40/65)] reason for refusing surgical treatment was high operative risk as assessed by the physicians who initially cared for the patients. Multivariate logistic regression analysis identified female gender, chronic renal insufficiency, older age, pneumonia, and emergent status as independent predictors of the conservative treatment. Patients with isolated aortic valve disease tended to undergo an operation. Overall 5-year survival in the surgical group was 76.8% versus 42.9% in the conservative group (P < 0.0001). After matching using the propensity score, the surgical group still had a better long-term survival than the conservative group (P = 0.001). Cox regression analysis revealed conservative treatment as the single risk factor associated with poor long-term survival in all series.Approximately 40% of the elderly patients with symptomatic severe heart valve disease were treated conservatively despite a definite indication for surgical intervention. Cardiac and geriatric co morbidities profoundly affect the treatment decision-making. Interdisciplinary discussion should be encouraged to optimize therapeutic options for elderly patients with valvular heart disease. PMID- 27396560 TI - Native Myocardial T1 Mapping, Are We There Yet? AB - T1 or longitudinal relaxation time is one of the very fundamental magnetic resonance imaging (MRI) time constants and a tissue characterizing parameter. Only during the last decade did it become possible to quantify T1 values of the myocardium through T1 mapping. Evolving from only region of interest analysis and long acquisition times to the pixel-based parametric mapping and short breath hold sequences, T1 mapping is reaching maturity among cardiac magnetic resonance (CMR) techniques. Both inversion recovery methods such as MOdified Look-Locker Inversion (MOL-LI) and Shortened MOLLI (ShMOLLI) and saturation recovery methods such as Saturation recovery Single-Shot Acquisition (SASHA) are available for T1 quantification with variable degrees of accuracy, precision, and reproducibility. Native (non-contrast) T1 values increase with edema, amyloid deposition, and fibrosis, while they decrease in fat or iron deposition in the myocardium. These features enabled significant expansion of the clinical applications of native T1 mapping where it provides high sensitivity and specificity and even acts as a disease biomarker or a predictor of prognosis. It is of particular usefulness in diffuse myocardial diseases where conventional CMR techniques might be deceiving. A brighter future for the technique is expected if certain challenges are to be faced, examples of which are the need for standardization of normal values, acquisition techniques, and improving analysis tools. PMID- 27396561 TI - Hyperuricemia and Atrial Fibrillation. AB - The importance of atrial fibrillation (AF) as a cause of mortality and morbidity has prompted research on its pathogenesis and treatment. Recognition of AF risk factors is essential to prevent it and reduce the risk of death. Hyperuricemia has been widely accepted to be associated with the incidence of paroxysmal or persistent AF, as well as to the risk of AF in post cardiovascular surgery patients. The possible explanations for this association have been based on their relation with either oxidative stress or inflammation. To investigate the link between hyperuricemia and AF, it is necessary to refer to hyperuricemia-induced atrial remodeling. So far, both ionic channel and structural remodeling caused by hyperuricemia might be plausible explanations for the occurrence of AF. Inhibition of xanthine oxidase and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, or the use of antioxidants, along with serum uric acid (SUA) level reduction to prevent inflammation, might be useful. Uric acid transporters (UATs) play a key role in the regulation of intracellular uric acid concentration. Intracellular rather than serum uric acid level is considered more important for the pathogenesis of AF. Identification of UATs expressed in cells is thus important, and targeting UATs might become a potential strategy to reduce the risk of hyperuricemia-induced atrial fibrillation. PMID- 27396562 TI - Hydrogen Sulfide, a Potential Cardioprotective Gas Activating a Life Span Regulator. PMID- 27396563 TI - Predictors for Tolvaptan Treatment and Future Perspectives. PMID- 27396564 TI - Bacterial pathogenesis: Mycobacteria that are long in the tooth. PMID- 27396565 TI - Unravelling the Laverania. AB - How did an ape-infecting Plasmodium species jump to a human host? PMID- 27396569 TI - Pgm report. PMID- 27396570 TI - Coming in postgraduate medicine. PMID- 27396566 TI - Influenza virus RNA polymerase: insights into the mechanisms of viral RNA synthesis. AB - The genomes of influenza viruses consist of multiple segments of single-stranded negative-sense RNA. Each of these segments is bound by the heterotrimeric viral RNA-dependent RNA polymerase and multiple copies of nucleoprotein, which form viral ribonucleoprotein (vRNP) complexes. It is in the context of these vRNPs that the viral RNA polymerase carries out transcription of viral genes and replication of the viral RNA genome. In this Review, we discuss our current knowledge of the structure of the influenza virus RNA polymerase, and insights that have been gained into the molecular mechanisms of viral transcription and replication, and their regulation by viral and host factors. Furthermore, we discuss how advances in our understanding of the structure and function of polymerases could help in identifying new antiviral targets. PMID- 27396567 TI - Metagenome-wide association studies: fine-mining the microbiome. AB - Metagenome-wide association studies (MWAS) have enabled the high-resolution investigation of associations between the human microbiome and several complex diseases, including type 2 diabetes, obesity, liver cirrhosis, colorectal cancer and rheumatoid arthritis. The associations that can be identified by MWAS are not limited to the identification of taxa that are more or less abundant, as is the case with taxonomic approaches, but additionally include the identification of microbial functions that are enriched or depleted. In this Review, we summarize recent findings from MWAS and discuss how these findings might inform the prevention, diagnosis and treatment of human disease in the future. Furthermore, we highlight the need to better characterize the biology of many of the bacteria that are found in the human microbiota as an essential step in understanding how bacterial strains that have been identified by MWAS are associated with disease. PMID- 27396571 TI - Problems/Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27396568 TI - Store-operated calcium entry is required for sustained contraction and Ca2+ oscillations of airway smooth muscle. AB - KEY POINTS: Airway hyper-responsiveness in asthma is driven by excessive contraction of airway smooth muscle cells (ASMCs). Agonist-induced Ca2+ oscillations underlie this contraction of ASMCs and the magnitude of this contraction is proportional to the Ca2+ oscillation frequency. Sustained contraction and Ca2+ oscillations require an influx of extracellular Ca2+ , although the mechanisms and pathways mediating this Ca2+ influx during agonist induced ASMC contraction are not well defined. By inhibiting store-operated calcium entry (SOCE) or voltage-gated Ca2+ channels (VGCCs), we show that SOCE, rather than Ca2+ influx via VGCCs, provides the major Ca2+ entry pathway into ASMCs to sustain ASMCs contraction and Ca2+ oscillations. SOCE may therefore serve as a potential target for new bronchodilators to reduce airway hyper responsiveness in asthma. ABSTRACT: Asthma is characterized by airway hyper responsiveness: the excessive contraction of airway smooth muscle. The extent of this airway contraction is proportional to the frequency of Ca2+ oscillations within airway smooth muscle cells (ASMCs). Sustained Ca2+ oscillations require a Ca2+ influx to replenish Ca2+ losses across the plasma membrane. Our previous studies implied store-operated calcium entry (SOCE) as the major pathway for this Ca2+ influx. In the present study, we explore this hypothesis, by examining the effects of SOCE inhibitors (GSK7975A and GSK5498A) as well as L-type voltage gated Ca2+ channel inhibitors (nifedipine and nimodipine) on airway contraction and Ca2+ oscillations and SOCE-mediated Ca2+ influx in ASMCs within mouse precision-cut lung slices. We found that both GSK7975A and GSK5498A were able to fully relax methacholine-induced airway contraction by abolishing the Ca2+ oscillations, in a manner similar to that observed in zero extracellular Ca2+ ([Ca2+ ]e ). In addition, GSK7975A and GSK5498A inhibited increases in intracellular Ca2+ ([Ca2+ ]i ) in ASMCs with depleted Ca2+ -stores in response to increased [Ca2+ ]e , demonstrating a response consistent with the inhibition of SOCE. However, GSK7975A and GSK5498A did not reduce Ca2+ release via IP3 receptors stimulated with IP3 released from caged-IP3 . By contrast, nifedipine and nimodipine only partially reduced airway contraction, Ca2+ oscillation frequency and SOCE-mediated Ca2+ influx. These data suggest that SOCE is the major Ca2+ influx pathway for ASMCs with respect to sustaining agonist-induced airway contraction and the underlying Ca2+ oscillations. The mechanisms of SOCE may therefore form novel targets for new bronchodilators. PMID- 27396573 TI - Washington Report on Health. PMID- 27396572 TI - What's Happening in Medicine! PMID- 27396574 TI - Editorials. PMID- 27396577 TI - Formation of defect-fluorite structured NdNiOxHy epitaxial thin films via a soft chemical route from NdNiO3 precursors. AB - A new phase of oxyhydride NdNiOxHy with a defect-fluorite structure was obtained by a soft chemical reaction of NdNiO3 epitaxial thin films on a substrate of SrTiO3 (100) with CaH2. The epitaxial relationship of this phase relative to SrTiO3 could be controlled by changing the reaction temperature. At 240 degrees C, NdNiOxHy grew with a [001] orientation, forming a thin layer of infinite-layer NdNiO2 at the interface between the NdNiOxHy and the substrate. Meanwhile, a high temperature reaction at 400 degrees C formed [110]-oriented NdNiOxHy without NdNiO2. PMID- 27396579 TI - Consanguinity and associated perinatal outcomes, including stillbirth. AB - BACKGROUND: Consanguinity defined as the sexual union between two related individuals has been previously an infrequent practice in Australia, but recently there has been migration from countries with widespread practice of consanguinity. There is limited and conflicting evidence in the literature that suggests consanguinity to be associated with adverse obstetric outcomes. AIM: To assess the effect of consanguinity on perinatal outcomes. MATERIALS AND METHODS: A retrospective analysis of singleton births over a ten-year period at an Australian tertiary hospital. The data were extracted from the hospital obstetric database and analysed for an association between consanguinity and perinatal outcomes, including stillbirth. Main outcome measures were stillbirth, threatened premature labour, fetal congenital abnormality, perinatal mortality and neonatal outcomes. RESULTS: There were 46 399 singleton births recorded over the ten-year study period, and 44 004 had consanguinity data available. The overall consanguinity rate was 5.5% (n = 2565), which remained consistent over the study period at our institution. Consanguinity was associated with higher rate of threatened premature labour (5.6% vs 4.7%, P = 0.003), fetal congenital abnormality (4.2% vs 3.1%, P = 0.004), perinatal mortality (2.4% vs 1.0%, P < 0.001) and reduced risk of hypertension in pregnancy (5.3% vs 3.4%, P < 0.001). Consanguinity was an independent risk factor for stillbirth with a relative risk of 2.88 (P < 0.001, 95% CI 1.98, 4.18). CONCLUSION: Women from consanguineous relationships are at higher risk of adverse perinatal outcomes, including stillbirth. Given the 5% prevalence of consanguinity in our obstetric population, these findings have significant implications for preconception counselling, obstetric care and health resource allocation. PMID- 27396580 TI - Effect of elastic band-based high-speed power training on cognitive function, physical performance and muscle strength in older women with mild cognitive impairment. AB - AIM: The effectiveness of resistance training in improving cognitive function in older adults is well demonstrated. In particular, unconventional high-speed resistance training can improve muscle power development. In the present study, the effectiveness of 12 weeks of elastic band-based high-speed power training (HSPT) was examined. METHODS: Participants were randomly assigned into a HSPT group (n = 14, age 75.0 +/- 0.9 years), a low-speed strength training (LSST) group (n = 9, age 76.0 +/- 1.3 years) and a control group (CON; n = 7, age 78.0 +/- 1.0 years). A 1-h exercise program was provided twice a week for 12 weeks for the HSPT and LSST groups, and balance and tone exercises were carried out by the CON group. RESULTS: Significant increases in levels of cognitive function, physical function, and muscle strength were observed in both the HSPT and LSST groups. In cognitive function, significant improvements in the Mini-Mental State Examination and Montreal Cognitive Assessment were seen in both the HSPT and LSST groups compared with the CON group. In physical functions, Short Physical Performance Battery scores were increased significantly in the HSPT and LSST groups compared with the CON group. In the 12 weeks of elastic band-based training, the HSPT group showed greater improvements in older women with mild cognitive impairment than the LSST group, although both regimens were effective in improving cognitive function, physical function and muscle strength. CONCLUSIONS: We conclude that elastic band-based HSPT, as compared with LSST, is more efficient in helping older women with mild cognitive impairment to improve cognitive function, physical performance and muscle strength. Geriatr Gerontol Int 2017; 17: 765-772. PMID- 27396578 TI - Transcending the prediction paradigm: novel applications of SHAPE to RNA function and evolution. AB - Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) provides information on RNA structure at single-nucleotide resolution. It is most often used in conjunction with RNA secondary structure prediction algorithms as a probabilistic or thermodynamic restraint. With the recent advent of ultra-high throughput approaches for collecting SHAPE data, the applications of this technology are extending beyond structure prediction. In this review, we discuss recent applications of SHAPE data in the transcriptomic context and how this new experimental paradigm is changing our understanding of these experiments and RNA folding in general. SHAPE experiments probe both the secondary and tertiary structure of an RNA, suggesting that model-free approaches for within and comparative RNA structure analysis can provide significant structural insight without the need for a full structural model. New methods incorporating SHAPE at different nucleotide resolutions are required to parse these transcriptomic data sets to transcend secondary structure modeling with global structural metrics. These 'multiscale' approaches provide deeper insights into RNA global structure, evolution, and function in the cell. WIREs RNA 2017, 8:e1374. doi: 10.1002/wrna.1374 For further resources related to this article, please visit the WIREs website. PMID- 27396581 TI - The common neural parasite Pseudoloma neurophilia causes altered shoaling behaviour in adult laboratory zebrafish (Danio rerio) and its implications for neurobehavioural research. PMID- 27396582 TI - A qualitative study of patient and professional perspectives of healthcare services for multiple sclerosis: implications for service development and policy. AB - Multiple sclerosis (MS) is a chronic degenerative condition, with heterogeneous symptoms, and an unpredictable prognosis. Previous literature suggests patients' experiences of healthcare are unsatisfactory. Primary care may play a key role in the management of people with MS (PwMS); however, provision of services for PwMS has received little focus in the primary care literature. This study aimed to explore perspectives and experiences of PwMS and healthcare professionals of UK healthcare services for MS. Semi-structured interviews were conducted with 24 PwMS, 13 Practice Nurses, 12 General Practitioners and 9 MS Specialist Nurses in northern England, between October 2012 and April 2014. Participants were purposively selected. Data were analysed thematically using constant comparative analysis. The theoretical framework of candidacy was used to interrogate data, with themes mapping onto the National Institute for Health and Care Excellence (NICE) guideline for MS. How PwMS interpreted symptoms as leading to candidacy for care dictated help-seeking. PwMS required additional support in identifying symptoms due to MS. Participants reported poor experiences of care including poor access to services, poor continuity of care and poor interpersonal interactions with perceptions of limited person-centredness. PwMS and professionals identified that MS-related disability and progression of symptoms required responsive care. Relational continuity enabled PwMS to feel understood, and professionals to holistically appraise symptoms and progression. In conclusion, continuity and patient-centredness of care are central to positive healthcare experiences for PwMS and professionals. Services need to be more accessible to ensure responsive and effective MS management. This study provides unique findings on the role of primary care for PwMS, and the relationship between findings and MS NICE guideline recommendations with implications for service delivery in the community. PMID- 27396583 TI - The 2016 Academic Emergency Medicine Consensus Conference, Shared Decision Making in the Emergency Department: Development of a Policy-relevant Patient-centered Research Agenda May 10, 2016, New Orleans, LA. AB - Shared decision making in emergency medicine has the potential to improve the quality, safety, and outcomes of emergency department (ED) patients. Given that the ED is the gateway to care for patients with a variety of illnesses and injuries and the safety net for patients otherwise unable to access care, shared decision making in the ED is relevant to numerous disciplines and the interests of the United States (U.S.) public. On May 10, 2016 the 16th annual Academic Emergency Medicine (AEM) consensus conference, "Shared Decision Making: Development of a Policy-Relevant Patient-Centered Research Agenda" was held in New Orleans, Louisiana. During this one-day conference clinicians, researchers, policy-makers, patient and caregiver representatives, funding agency representatives, trainees, and content experts across many areas of medicine interacted to define high priority areas for research in 1 of 6 domains: 1) diagnostic testing; 2) policy, 3) dissemination/implementation and education, 4) development and testing of shared decision making approaches and tools in practice, 5) palliative care and geriatrics, and 6) vulnerable populations and limited health literacy. This manuscript describes the current state of shared decision making in the ED context, provides an overview of the conference planning process, the aims of the conference, the focus of each respective breakout session, the roles of patient and caregiver representatives and an overview of the conference agenda. The results of this conference published in this issue of AEM provide an essential summary of the future research priorities for shared decision making to increase quality of care and patient-centered outcomes. PMID- 27396584 TI - MR imaging, targeting and characterization of pulmonary fibrosis using intra tracheal administration of gadolinium-based nanoparticles. AB - Idiopathic pulmonary fibrosis is a devastating disease. Animal models are critical to develop new diagnostic approaches. We investigate here whether the application of an ultra-short echo time MRI sequence combined with the intra tracheal administration of Gd-based nanoparticles can help to visualize and characterize pulmonary fibrosis in mice. 21 mice were imaged. Treated mice were administered bleomycin. MRI was used for longitudinal detection of bleomycin induced lung injury from Day 1 up to Day 60. On Day 30, all mice received nanoparticles and MR images were acquired. A signal enhancement of 120% and 50% in fibrotic lesions and healthy tissues respectively was obtained. A twofold increase of contrast-to-noise ratio between fibrotic and healthy tissue was also observed, leading to a more accurate delineation of the extent of fibrosis. The elimination time constant of the nanoparticles was 54% higher in fibrotic lesions. Bleomycin-induced lung injury can be monitored using MRI. Intra-tracheal administration of Gd-based nanoparticles enabled us to enhance fibrotic tissue in lungs but also to extract imaging biomarkers that quantify elimination and diffusion of contrast agents and can characterize fibrotic tissue. The added value of MRI associated with pulmonary administration of contrast agents is key to better understand the lung fibrotic process and monitor drug response in pre clinical studies, which will be valuable for translational applications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27396585 TI - Encapsulating Subsite Analogues of the [FeFe]-Hydrogenases in Micelles Enables Direct Water Interactions. AB - Encapsulation of subsite analogues of the [FeFe]-hydrogenase enzymes in supramolecular structures has been shown to dramatically increase their catalytic ability, but the molecular basis for this enhancement remains unclear. We report the results of experiments employing infrared absorption, ultrafast infrared pump probe, and 2D-IR spectroscopy to investigate the molecular environment of Fe2(pdt)(CO)6 (pdt: propanedithiolate) [1] encapsulated in the dispersed alkane phase of a heptane-dodecyltrimethylammonium bromide-water microemulsion. It is demonstrated that 1 is partitioned between two molecular environments, one that closely resembles bulk heptane solution and a second that features direct hydrogen-bonding interactions with water molecules that penetrate the surfactant shell. Our results demonstrate that the extent of water access to the normally water-insoluble subsite analogue 1 can be tuned with micelle size, while IR spectroscopy provides a straightforward tool that can be used to measure and fine tune the chemical environment of catalyst species in self-assembled structures. PMID- 27396586 TI - Extinct or still out there? Disentangling influences on extinction and rediscovery helps to clarify the fate of species on the edge. AB - Each year, two or three species that had been considered to be extinct are rediscovered. Uncertainty about whether or not a species is extinct is common, because rare and highly threatened species are difficult to detect. Biological traits such as body size and range size are expected to be associated with extinction. However, these traits, together with the intensity of search effort, might influence the probability of detection and extinction differently. This makes statistical analysis of extinction and rediscovery challenging. Here, we use a variant of survival analysis known as cure rate modelling to differentiate factors that influence rediscovery from those that influence extinction. We analyse a global data set of 99 mammals that have been categorized as extinct or possibly extinct. We estimate the probability that each of these mammals is still extant and thus estimate the proportion of missing (presumed extinct) mammals that are incorrectly assigned extinction. We find that body mass and population density are predictors of extinction, and body mass and search effort predict rediscovery. In mammals, extinction rate increases with body mass and population density, and these traits act synergistically to greatly elevate extinction rate in large species that also occurred in formerly dense populations. However, when they remain extant, larger-bodied missing species are rediscovered sooner than smaller species. Greater search effort increases the probability of rediscovery in larger species of missing mammals, but has a minimal effect on small species, which take longer to be rediscovered, if extant. By separating the effects of species characteristics on extinction and detection, and using models with the assumption that a proportion of missing species will never be rediscovered, our new approach provides estimates of extinction probability in species with few observation records and scant ecological information. PMID- 27396588 TI - Immunoaffinity-coupled MS: best of both technologies. PMID- 27396589 TI - Cognitive Function and the Ageing Process: The Peculiar Role of Mild Thyroid Failure. AB - BACKGROUND: Over the last decades an increasing body of evidence suggested a possible relationship between thyroid hormone (TH) and the ageing process, and several efforts have been made to determine the actual role of TH dynamic during human life. It is still unclear whether the serum level shift of Thyroid Stimulating Hormone toward higher value, observed during ageing, is a normal adaptive response associated with senescence or an actual mild thyroid dysfunction. A growing body of evidence supports the hypothesis of a reset of the hypothalamus-pituitary-thyroid axis in order to contrast the catabolic status of the ageing process. On the other hand, several meta-analyses showed a direct link between subclinical hypothyroidism (sHT) and cardiovascular events (both ischemic heart disease and stroke), although mainly in individuals younger than 65 years. Similarly, a recent meta-analysis documented consistent data on a positive relationship between sHT and cognitive impairment, but only in individuals younger than 75 years. CONCLUSION: The available data suggest a complex relationship between mild thyroid failure and the ageing process as well as the development and progression of several cardiovascular and neurological diseases. In this paper, we reviewed the scientific English literature on sHT and the ageing process focusing on experimental evidences related to cognitive impairment and dementia. Moreover, we focused on new patents of treatments potentially able to improve the care of sHT patients, especially in the elderly, where treatment drawbacks may have negative impact on the long term outcome. PMID- 27396590 TI - Evaluation of the New Centers for Disease Control and Prevention Ventilator Associated Event Module and Criteria in Critically Ill Children in Greece. AB - OBJECTIVE To evaluate the new adult Centers for Disease Control and Prevention (CDC) ventilator-associated event (VAE) module in critically ill children and compare with the traditionally used CDC definition for ventilator-associated pneumonia (VAP). DESIGN Retrospective observational study of mechanically ventilated children in a pediatric intensive care unit in Greece January 1 December 31, 2011. METHODS Assessment of new adult CDC VAE module including 3 definition tiers: ventilator-associated condition (VAC), infection-related VAC, and possible/probable ventilator-associated pneumonia (VAE-VAP); comparison with traditional CDC criteria for clinically defined pneumonia in mechanically ventilated children (PNEU-VAP). We recorded Pediatric Risk of Mortality score at admission (PRISM III), number of ventilator-days, and outcome. RESULTS Among 119 patients with mechanical ventilation (median [range] number of ventilator-days, 7 [1-183]), 19 patients experienced VAC. Criteria for VAE-VAP were fulfilled in 12 of 19 patients with VAC (63%). Children with either VAC or VAE-VAP were on ventilation more days than patients without these conditions (16.5 vs 5 d, P=.0006 and 18 vs 5 d, P<.001, respectively), whereas PRISM-III score was similar between them. Mortality was significant higher in patients with new VAE-VAP definition (50%), but not in patients with VAC (31.6%), than the patients without new VAE-VAP (14%, P=.007) or VAC (15%, P=.1), respectively. No significant association was found between PNEU-VAP and death. Incidences of PNEU-VAP and VAE VAP were similar, but the agreement was poor. CONCLUSIONS VAE-VAP and PNEU-VAP found similar prevalence in critically ill children but with poor agreement. However, excess of death was significantly associated only with VAE-VAP. Infect Control Hosp Epidemiol 2016:1-5. PMID- 27396591 TI - Cinchona Urea-Catalyzed Asymmetric Sulfa-Michael Reactions: The Bronsted Acid Hydrogen Bonding Model. AB - The cinchona alkaloid-derived urea-catalyzed asymmetric conjugate addition of aromatic thiols to cycloalkenones was studied using density functional theory (DFT). Deprotonation of the thiol gives a protonated amine that activates the electrophile by Bronsted acid catalysis, while the urea group binds the nucleophilic thiolate by hydrogen bonding. These results demonstrate the generality of the Bronsted acid-hydrogen bonding transition state (TS) model for cinchona alkaloid catalysis that we recently showed to be favored over Wynberg's widely accepted ion pair-hydrogen bonding model and represent the first detailed mechanistic study of a cinchona urea-catalyzed reaction. The conformation of the catalyst methoxy group has a strong effect on the TS, an effect overlooked in previous mechanistic studies of reactions catalyzed by cinchona alkaloids. PMID- 27396592 TI - Dramatically Enhanced Mechanosensitivity and Signal-to-Noise Ratio of Nanoscale Crack-Based Sensors: Effect of Crack Depth. AB - The sensitivity of a nanoscale crack-based sensor is enhanced markedly by modulating the crack depth. The crack-depth-propagated sensor exhibits ~16 000 gauge factor at 2% strain and a superior signal-to-noise ratio of ~35, which facilitates detection of target signals for voice-pattern recognition. PMID- 27396593 TI - Emerging Role for RBM20 and its Splicing Substrates in Cardiac Function and Heart Failure. AB - Heart failure is one of the devastating public health problems with high mortality. Among various contributing factors for heart failure, severe dilated cardiomyopathy is the most common indication for cardiac transplantation. Recent evidence revealed that RBM20 mutation represents one main cause for familial dilated cardiomyopathy with a 3% prevalence in all forms of dilated cardiomyopathy. Further scrutiny of molecular mechanisms suggests a role for RBM20 as a functional splicing factor for protein isoform transition, indicating the clinical value of RBM20 mutations in the diagnosis and treatment of heart diseases. RBM20 alternatively splices a set of genes including titin, CaMKIID, and GIT2 at the post transcriptional level to yield diverse isoforms. These target proteins are necessary for cardiac homeostasis including structure and signal transduction. Mutations in RBM20 cause dilated cardiomyopathy along with dysregulated isoform switch. This review aims to summarize the current knowledge of RBM20-related dilated cardiomyopathy and heart failure as well as the underlying mechanism. We will emphasize and thoroughly discuss two splicing targets including titin and CaMKII which are known to play a vital role in dilated cardiomyopathy and heart failure. PMID- 27396594 TI - The Influence of Tetracycline Inducible Targeting Rat PPARgamma Gene Silencing on the Osteogenic and Adipogenic Differentiation of Bone Marrow Stromal Cells. AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) has been considered as the master regulator for adipogenesis of bone marrow stromal cells (BMSCs). However, there are few reports regarding the effect of PPARgamma gene silencing on osteogenic and adipogenic differentiation in rat BMSCs, and no reports about tissue targeting and conditional knockdown of PPARgamma gene. In this study, we construct rat PPARgamma gene shRNA Tet-on lentiviral vector, the lentiviral vector facilitated tetracycline (which has the characteristics of bone targeting) inducible knockdown specific to PPARgamma gene, and transfect it into BMSCs, the silencing effects induced by tetracycline is significant. The expression of the adipogenic factors adipocyte determination and differentiation-dependent factor 1 (ADD1) and recombinant CCAAT/enhancer binding protein alpha (C/EBPalpha) were decreased as measured by RT-PCR and Western blot assay following PPARgamma silencing. In contrast, expression of the osteogenic genes encoding collagen I and Cbfa1/Runx2 were increased. In adipogenic medium, PPARgamma-shRNA transfection reduced the lipid droplet count as measured by Oil red O staining when compared to the control groups. In osteogenic medium, PPARgamma-shRNA increased the activity of alkaline phosphatase and the amount of calcium deposition as measured by Alizarin red S staining. These results suggest that the rat PPARgamma gene shRNA Teton lentiviral vector decreases adipogenic differentiation and promotes osteogenic differentiation in BMSCs induced by tetracycline. PMID- 27396595 TI - Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis. AB - AIMS: The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. METHODS: For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). RESULTS: The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. CONCLUSION: Natalizumab normalizes altered melatonin and norepinephrine levels in MS. PMID- 27396596 TI - The Gradually Expanding Scope for Biowaivers of Oral Products: An Overview. AB - The regulatory paradigm is relaxing gradually without compromising the safety, efficacy and the quality of the drug product and, most importantly, a perceptible scientific consensus is maturing towards the need of affordable medicines. The establishment of bioequivalence (BE) is no longer being considered to be accomplished only by in vivo studies in oral drug products. The potential use of in vitro dissolution testing in lieu of BE studies has now been regulatory adopted and is commonly referred to as "biowaiver". Further, the advent of biopharmaceutics classification system (BCS) and in vitro-in vivo correlation (IVIVC) proves to be sound milestones and signifies that we are incessantly forwarding towards a scenario that would reduce regulatory burden, save time and make the drug products more affordable while ensuring their quality. This review outlines, the current and pertinent regulatory environment for biowaiver based on in vitro drug dissolution, primarily as per the FDA perspective. The rationale used for qualification of biowaiver for different strengths, post-approval changes and multi-source products are discussed along with the role of BCS and IVIVC. PMID- 27396597 TI - The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders. AB - Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs. PMID- 27396598 TI - Lipid-Based Nanocarriers for Cutaneous Leishmaniais and Buruli Ulcer Management. AB - Infectious diseases in the skin represent a major group of pathologies that contribute annually for significant health economic expenses. According to WHO, Buruli Ulcer (BU) and Cutaneous Leishmaniasis (CL) are two neglected tropical diseases for which therapy remains inadequate. Topical delivery of therapeutics constitutes an advantageous alternative to treat infected skin lesions as it allows a direct treatment of affected areas avoiding unwanted systemic effects and reducing the drug dosage. However, effective topical delivery of antimicrobial agents is still a challenge. The emergence of difficult-to-treat skin mycobacteriosis such as BU or the increasing incidence of CL highlights the need for new antimicrobial agents and new delivery systems. In the present review problems related to mycobacterial and parasitic infected skin lesions will be particularly focused as well as new alternative strategies for their treatment. Currently, progresses and challenges in constructing nanocarrier platforms for delivering various antimicrobial drugs for infected skin lesions have been attempted. This article reviews the potential of these nanocarriers in the treatment of cutaneous infections, especially regarding mycobacteria and Leishmania caused skin lesions. Nanostructured biomaterials, such as lipid-based nanocarriers, have unique physicochemical properties enabling the topical application of antimicrobial drugs, thereby overcoming some of the limitations of conventional therapies. These nanosystems have been investigated for the topical delivery of well-known drugs or new therapeutic candidates. This approach is just the beginning of a stimulating nanotechnological area. PMID- 27396599 TI - Energy Remodeling, Mitochondrial Disorder and Heart Failure. AB - Heart failure (HF) is a major global problem in public health with no curative treatment currently available. Energy remodeling is one of the features in HF, preceding cardiac structure remodeling. As an important energy organelle, mitochondrion plays critical roles in the progress of HF. This review focuses on the potential mechanisms linking mitochondrial functions and energy remodeling in HF including the energy starvation theory and energy substrate metabolism. It also highlights the potentials of novel drugs targeting HF energy metabolism. PMID- 27396600 TI - Targeting Mitochondrial Dysfunction in Chronic Heart Failure: Current Evidence and Potential Approaches. AB - BACKGROUND: Mitochondria are cellular organelles responsible for energy production, calcium handling, controlled synthesis of reactive oxygen species (ROS), and regulation of apoptosis. All these functions are crucial for cardiac homeostasis, and may be impaired in chronic heart failure (CHF). Therefore, mitochondrial dysfunction might represent a crucial element in the onset and progression of CHF and, as such, a promising therapeutic target. METHODS: Original articles and review on the treatment of mitochondrial dysfunction in CHF were searched on Medline and Scopus. RESULTS: The present review summarizes the current knowledge about mitochondrial modulation as a therapeutic strategy for CHF, and proposes some perspectives for future studies. Mitochondrial dysfunction can be ascribed to neuro-humoral activation and cardiac remodeling associated with CHF. Conceptually, the correction of mitochondrial dysfunction could provide an additive benefit to optimal CHF treatment. Increasing glucose metabolism and reducing oxidative stress within mitochondria are the two most promising approaches, even though further studies are required before implementing new treatments in the setting of CHF. On the other hand, inhibition of apoptosis, and normalization of calcium and mitochondrial dynamics have been assessed almost exclusively in ex vivo models, and mostly in settings other than CHF. CONCLUSION: Mitochondrial modulation in CHF is an intriguing example of translational research and a potentially rewarding field. PMID- 27396601 TI - Lipids, Statins and Heart Failure: An Update. AB - BACKGROUND: Heart failure (HF) is characterized by cardiac functional and structural alterations, progressively leading to clinical symptoms and signs. Certain neurohormonal systems (i.e. the sympathetic nervous system, the reninangiotensin-aldosterone system and the natriuretic peptide system) as well as interactions between endothelial, monocytes/macrophages and myocardial cells are involved in the process. METHODS: The present narrative review discusses the relationships between lipids, statins and HF. RESULTS: Lipid metabolism is involved in cardiac function. Inflammation, oxidative stress, endothelial and platelet dysfunction, activation of neurohormonal systems, adverse cardiac remodeling, haemodynamic disorders and arrhythmogenesis predispose to HF development and progression. Statins have been shown to reduce HF incidence possibly via their pleiotropic actions on the above mentioned mechanisms. Other cardiovascular (CV) risk factors affecting HF prevalence and outcomes include metabolic syndrome, non-alcoholic fatty liver disease, chronic kidney disease, hyperuricaemia, epicardial fat and increased arterial stiffness that are improved following statin therapy. CONCLUSION: Lipid disorders are involved in HF development and progression. Statins may beneficially affect these disorders as well as other CV risk factors linked to HF. However, the impact of statins in patients with established HF has yet to be determined. Further studies are needed to unveil potential benefits of statin therapy (or some statins) in specific groups of HF patients. PMID- 27396602 TI - Design and Synthesis of 2-(Arylmethylideneamino) Isoindolines as New Potential Analgesic and Anti-Inflammatory Agents: A Molecular Hybridization Approach. AB - Phthalimide and hydrazine pharmacophores have been demonstrated to be inhibitors of cyclooxygenases (COX) and lipoxygenases (LOX) and to possess a marked analgesic and anti-inflammatory activity. A new group of hybrid analogs of phthalimide and hydrazine (2-(arylmethylideneamino) isoindolines), possessing a variety of substituents (OMe, OH, NO2, Cl, and F) at different positions of the aryl ring, were synthesized and their analgesic and anti-inflammatory effects were evaluated. In vivo screening showed that all the analogs possessed analgesic and anti-inflammatory activity and compounds 10g, 10h and 10e were the most potent as analgesic and compounds 10b, 10c and 10i were the most potent as anti inflammatory agents. PMID- 27396603 TI - Photoinduced 2-way electron transfer in composites of metal nanoclusters and semiconductor quantum dots. AB - In order to explore the potential of nanocomposites comprising semiconductor quantum dots (QDs) and metal nanoclusters (NCs) in photovoltaic and catalytic applications, the interaction between CdTe QDs and gold NCs, Au10 and Au25, stabilized by histidine, bovine serum albumin (BSA) and glutathione, is studied by an ultrafast transient absorption (TA) technique. Temporal and spectral studies of the transients reveal photoinduced 2-way electron transfer between the two constituents of the nanocomposites, where Au NCs, which generally act as electron donors when used as photosensitizers, perform the role of the efficient electron acceptor. Interestingly, it is found that the electron transfer dynamics in these composites is governed not by the distance of separation of the constituents but by the nature of the surface capping ligands. Despite a large separation between the QDs and NCs in a giant BSA-capped system, a higher electron transfer rate in this composite suggests that unlike other smaller capping agents, which act more like insulators, BSA allows much better electron conduction, as indicated previously. PMID- 27396604 TI - Inhibition of Aurora A Kinase by Alisertib Induces Autophagy and Cell Cycle Arrest and Increases Chemosensitivity in Human Hepatocellular Carcinoma HepG2 Cells. AB - BACKGROUND: Aurora A kinase represent a feasible target in cancer therapy. OBJECTIVE: To evaluate the proteomic response of human liver carcinoma cells to alisertib (ALS) and identify the molecular targets of ALS, we examined the effects of ALS on the proliferation, cell cycle, autophagy, apoptosis, and chemosensitivity in HepG2 cells. METHOD: The stable-isotope labeling by amino acids in cell culture (SILAC) based quantitative proteomic study was performed to evaluate the proteomic response to ALS. Cell cycle distribution and apoptosis were assessed using flow cytometry and autophagy was determined using flow cytometry and confocal microscopy. RESULTS: Our SILAC proteomic study showed that ALS regulated the expression of 914 proteins, with 407 molecules being up regulated and 507 molecules being down-regulated in HepG2 cells. Ingenuity pathway analysis (IPA) and KEGG pathway analysis identified 146 and 32 signaling pathways were regulated by ALS, respectively, which were associated with cell survival, programmed cell death, and nutrition-energy metabolism. Subsequently, the verification experiments showed that ALS remarkably arrested HepG2 cells in G2/M phase and led to an accumulation of aneuploidy via regulating the expression of key cell cycle regulators. ALS induced a marked autophagy in a concentration- and time-dependent manner via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Autophagy inhibition promoted the pro-apoptotic effect of ALS, indicating a cyto-protective role of ALS-induced autophagy. ALS increased the chemosensitivity of HepG2 cells to cisplatin and doxorubicin. CONCLUSION: Taken together, ALS induces autophagy and cell cycle arrest in HepG2 cells via PI3K/Akt/mTOR-mediated pathway. Autophagy inhibition may promote the anticancer effect of ALS and sensitize the chemotherapy in HepG2 cells. PMID- 27396605 TI - Malondialdehyde and 4-hydroxy-2-hexenal are formed during dynamic gastrointestinal in vitro digestion of cod liver oils. AB - Marine long-chain polyunsaturated fatty acids (LC n-3 PUFA) are associated with reduced risk for inflammatory diseases, such as cardiovascular diseases and rheumatoid arthritis. These fatty acids, however, are rapidly oxidized, generating highly reactive malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4 hydroxy-2-nonenal (HNE). These oxidation products may interact with DNA and proteins, thus possibly leading to impaired cell functions. Little is known about the formation of MDA, HHE and HNE in fish oil in the gastrointestinal (GI) tract. In this study, the effect of dynamic in vitro digestion of cod liver oil on the generation of MDA, HHE and HNE was evaluated using the TNO Gastro-Intestinal Model (tiny-TIM). Effects of pre-formed oxidation products, pre-emulsification of the oil, and addition of oxidants (EDTA and hemoglobin, Hb) on GI oxidation were evaluated. Formation of aldehydes occurred during GI digestion. However, only emulsified oil fortified with 11.5 MUM Hb oxidized to a degree that overcame the dilution induced by gastric secretion, which caused increased aldehyde concentrations in gastric lumen up to 90 min. The maximum levels of aldehydes generated in this study were 24.5 MUM MDA, 1.6 MUM HHE and 0.07 MUM HNE. Oils containing different amounts of pre-formed lipid oxidation products maintained the same oxidation ranking order during digestion, even though the relative changes were not directly proportional. Emulsification of the oil had an unclear effect in the gastric phase, but a pro-oxidative effect in the intestinal phase. In general, higher aldehyde levels were reached in the intestinal lumen than in the initial meal, demonstrating that GI digestion promotes oxidation. Hence, epithelial cells may be exposed to elevated amounts of reactive aldehydes for several hours after a meal containing fish oil. PMID- 27396606 TI - When we should say no to TAVR-Defining the line between utility and futility. AB - History of prior coronary artery bypass surgery (CABG) is a frequent scenario encountered in patients with severe symptomatic aortic stenosis deemed inoperable and referred for transcatheter aortic valve replacement (TAVR). Aside from indices of frailty and other comorbidities, these patients remain at higher risk for peri-operative mortality and morbidity compared to their counterparts without prior CABG. Presence of concomitant peripheral arterial disease and patent left internal mammary artery (LIMA) graft pose further access related challenges. We present a case of an 84-year-old female with prior CABG and severe PAD who underwent transapical TAVR for severe symptomatic AS sustaining an acute myocardial injury from damage to her apical epicardial collateral circulation. The case entails the importance of recognition of epicardial coronary collateralization where a transapical approach is best avoided or further aided by utilization of peri-procedural angiographic/fluoroscopy guidance to avoid epicardial vascular injury. PMID- 27396607 TI - Incidence, feasibility and outcome of percutaneous coronary intervention after transcatheter aortic valve implantation with a self-expanding prosthesis. Results from a single center experience. AB - OBJECTIVES: Percutaneous coronary intervention (PCI) after transcatheter aortic valve implantation (TAVI) can become technically challenging after implantation of the self-expanding Medtronic CoreValve (MCV) device, which completely covers the aortic root. The aim of this study was to report on the incidence, feasibility and outcome of PCI after TAVI with the MCV device. METHODS: Between 2007 and 2014, all patients subjected to PCI after MCV implantation in a single center institutional TAVI database were retrospectively identified. Clinical, angiographic and procedural characteristics were reviewed and analyzed. RESULTS: We identified a total of 17 patients (5.7%) treated with 24 PCI procedures for 29 lesions at a median of 17.7months (range 1-72) after MCV implantation. The mean age was 79.7+/-6.8years and the mean logistic EuroSCORE was 30.3%+/-18.9%. Nine procedures were performed for patients with acute coronary syndrome. 89.6% of the treated lesions were of type B2/C and 79.3% were de novo ones. A median of one guiding catheter was necessary to intubate the target coronary ostium (range 1 10) and 95% of the lesions on the left coronary artery were treated through a Judkins catheter. In one primary PCI for STEMI the intubation of the right coronary ostium was not successful. Final procedural success was obtained in 95.8%, and peri-procedural death occurred in one patient. CONCLUSIONS: The need for PCI after MCV is not uncommon and is mostly related to coronary artery disease progression. PCI after MCV is usually feasible and safe, but coronary intubation in an emergency setting can be challenging. PMID- 27396609 TI - Comparison of whole genome sequencing typing results and epidemiological contact information from outbreaks of Salmonella Dublin in Swedish cattle herds. AB - BACKGROUND: Whole genome sequencing (WGS) is becoming a routine tool for infectious disease outbreak investigations. The Swedish situation provides an excellent opportunity to test the usefulness of WGS for investigation of outbreaks with Salmonella Dublin (S. Dublin) as epidemiological investigations are always performed when Salmonella is detected in livestock production, and index isolates from all detected herds are stored and therefore available for analysis. This study was performed to evaluate WGS as a tool in forward and backward tracings from herds infected with S. Dublin. MATERIAL AND METHODS: In this study, 28 isolates from 26 cattle herds were analysed and the WGS results were compared with results from the epidemiological investigations, for example, information on contacts between herds. The isolates originated from herds in three different outbreaks separated geographically and to some extent also in time, and from the only region in Sweden where S. Dublin is endemic (Oland). RESULTS: The WGS results of isolates from the three non-endemic regions were reliably separated from each other and from the endemic isolates. Within the outbreaks, herds with known epidemiological contacts generally showed smaller differences between isolates as compared to when there were no known epidemiological contacts. CONCLUSION: The results indicate that WGS can provide valuable supplemental information in S. Dublin outbreak investigations. The resolution of the WGS was sufficient to distinguish isolates from the different outbreaks and provided additional information to the investigations within an outbreak. PMID- 27396610 TI - Discovery and Structural Optimization of N5-Substituted 6,7-Dioxo-6,7 dihydropteridines as Potent and Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors against L858R/T790M Resistance Mutation. AB - EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR inhibitor (compound 9), we present a structure-based design approach, which is rationalized via analyzing its binding model and comparing the differences of gatekeeper pocket between the T790M mutant and wild-type (WT) EGFR kinases. Guided by these results, a novel 6,7-dioxo-6,7-dihydropteridine scaffold was discovered and hydrophobic modifications at N5-position were conducted to strengthen nonpolar contacts and improve mutant selectivity over EGFR(WT). Finally, the most representative compound 17d was identified. This work demonstrates the power of structure-based strategy in discovering lead compounds and provides molecular insights into the selectivity of EGFR(L858R/T790M) over EGFR(WT), which may play an important role in designing new classes of mutant selective EGFR inhibitors. PMID- 27396611 TI - Quantifying the dynamic transition of hydrogenated castor oil gels measured via multiple particle tracking microrheology. AB - Rheological modifiers are essential ingredients in commercial materials that exploit facile and repeatable phase transitions. Although rheological modifiers are used to change flow behavior or quiescent stability, the complex properties of particulate gels during dilution is not well studied. We characterize a dynamically evolving colloidal gel, hydrogenated castor oil (HCO), a naturally sourced material, used in consumer products. This HCO scaffold consists of fibrous colloids, a surfactant (linear alkylbenzene sulfonate) and water. The gel undergoes critical transitions, degradation and formation, in response to an osmotic pressure gradient. Multiple particle tracking microrheology (MPT) measures the evolving material properties. In MPT, fluorescent probe particles are embedded into the sample and Brownian motion is measured. MPT data are analyzed using time-cure superposition, identifying critical transition times and critical relaxation exponents for degradation and formation where tc,deg = 102.5 min, ndeg = 0.77 +/- 0.09, tc,for = 31.9 min, and nfor = 0.94 +/- 0.11, respectively. During degradation and formation HCO gels evolve heterogeneously, this heterogeneity is characterized spatially and temporally. Heterogeneity of the gel is quantified by comparing variances of single particle van Hove correlation functions using an F-test with a 95% confidence interval. HCO transitions have rheological heterogeneous microenvironments that are homogeneously distributed throughout the field of view. Although HCO gels do evolve heterogeneously, this work determines that these heterogeneities do not significantly change traditional MPT measurements but the analysis techniques developed provide additional information on the unique heterogeneous scaffold microenvironments. This creates a toolbox that can be widely applied to other scaffolds during dynamic transitions. PMID- 27396612 TI - Prevalence and risk factors of erosive tooth wear in 3-6 year old German kindergarten children-A comparison between 2004/05 and 2014/15. AB - OBJECTIVES: The aims of this study were (1) to investigate prevalence, severity and distribution of erosive tooth wear in German kindergarten children aged 3-6 years in 2014/15 in comparison to an earlier survey from 2004/05 and (2) to identify and compare possible risk factors. METHODS: 775 children aged 3-6 years from 27 kindergartens were examined in 2014/15 and compared to the data from 2004/05 (432 children/21 kindergartens). Erosive tooth wear was examined using the O'Sullivan-Index. Additionally, data were converted into the Basic Erosive Wear Examination (BEWE)-index. Information about dietary habits, chronic illness and oral hygiene practices were obtained by questionnaires. Statistical analyses were done by Chi(2)-, Mann-Whitney U Tests and regression analyses (p<0.05). RESULTS: Compared to 2004/05 (31.3%) prevalence of erosive tooth wear was significantly increased in 2014/15 (45.4%). In 2004/05 and 2014/15, prevalence increased significantly with increasing age of the children: 3-year-olds: 22.5%/14.2%; 4-year-olds: 27.4%/32.9%; 5-year-olds: 30.5%/58.8%; 6-year-olds: 38.1%/71.7%. Children with erosive tooth wear presented more affected teeth and a higher severity of erosive tooth wear, respectively, in 2014/15 compared to 2004/05. The BEWE score sum was significantly higher in 2014/15 (3-year-olds: 3.4+/-2.1, 4-year-olds: 4.2+/-3.1, 5-year-olds: 4.6+/-2.9, 6-year-olds: 5.9+/ 3.3) than in 2004/05 (3-year-olds: 2.0+/-1.2, 4-year-olds: 2.7+/-1.8, 5-year olds: 2.7+/-2.4, 6-year-olds: 4.2+/-4.2). In 2014/15, age and male gender were significant with respect to the presence of erosive tooth wear. Severity of erosive tooth wear was dependent on the regular consumption of fruit juices and lemonade/coke. CONCLUSION: The prevalence of erosive tooth wear in German kindergarten children has increased in the last ten years. PMID- 27396613 TI - Ebola hemorrhagic fever under scope, view of knowledge, attitude and practice from rural Sudan in 2015. AB - Ebola hemorrhagic fever (EHF) is an emerging threat to public health. The last epidemic in West Africa had a great effect on the affected communities. Timely and effective interventions were necessary in addition to community participation to control the epidemic. The knowledge, attitude and practices of vulnerable communities remain unknown, particularly in Sudan. The aim of this study was to explore the knowledge, attitude and practices of rural residents in Sudan regarding Ebola hemorrhagic fever. We conducted a cross sectional, community based large-scale study in Al Gaziera state in rural Sudan in eight localities. In total, 1500 random adult participants were selected. The participants were assessed by a predesigned pretested questionnaire regarding their knowledge, attitude and practices regarding Ebola. Their sources of information were determined, and we assessed demographic factors as predictors of knowledge. We found poor knowledge, a fair attitude and suboptimal practices among the participants. The main sources of information were the press and media. Education was the only predictor of knowledge regarding Ebola. A lack of knowledge and suboptimal preventive practices mandates orientation and education programs to raise public awareness. Health care providers are advised to engage more in educating the community. PMID- 27396614 TI - Detecting long-term temporal trends in sediment-bound trace metals from urbanised catchments. AB - The shift from rural lifestyles to urban living has dramatically altered the way humans interact and live across the globe. With over 50% of the world's populations living within cities, and significant increases expected over the next 50 years, it is critical that changes to social, economic and environmental sustainability of cities globally be implicit. Protecting and enhancing aquatic ecosystems, which provide important ecosystem services, is challenging. A number of factors influence pollutants in urban waterways including changes in land-use, impervious area and stormwater discharges, with sediment-bound pollution a major issue worldwide. This work aimed to investigate the spatial and temporal distribution of trace metals in freshwater sediments from six urbanised catchment over a 30-year period. It provides an estimate of pollution using a geoaccumulation index and examines possible toxicity using a probable effect concentration quotient (mPECq). Results showed significant temporal changes in metal concentrations over time, with lead generally decreasing in all but one of the sites, attributed to significant changes in environmental policies and the active elimination of lead products. Temporal changes in other metals were variable and likely dependent on site-specific factors. While it is likely that diffuse pollution is driving changes in zinc, for metals such as lead, chromium and copper, it is likely that watershed landuse and/or point sources are more important. The results clearly indicated that changes to watershed landuse, environmental policy and pollution abatement programs are all driving changes in sediment quality, highlighting the utility of long-term sediment monitoring for assessment of urban watershed condition. While this study has demonstrated the utility of detecting long-term changes in metal concentrations, this approach could easily be adapted to detect and assess future trends in other hydrophobic contaminants and emerging chemicals of concern, such as synthetic pyrethroids, providing essential information for the protection of catchment. PMID- 27396615 TI - Bioaccumulation of organochlorine pesticides and polychlorinated biphenyls by loaches living in rice paddy fields of Northeast China. AB - The concentrations of 21 organochlorine pesticide (OCP) residues and 18 polychlorinated biphenyl (PCB) congeners were measured in two loach species (Misgurnus mohoity and Paramisgurnus dabryanus) and the soils of their inhabiting rice paddies from three typical rice production bases of Northeast China to explore the main factors influencing the bioaccumulation. The concentrations of ?18PCBs and ?21OCPs in loaches were determined to be in the ranges of 0.14-0.76 ng g(-1) wet weight (ww) and 1.19-78.53 ng g(-1) ww, respectively. Most of loaches showed the considerably high contamination levels of dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), which accounted for over 97% of the total OCPs. The much lower maximum allowable loach consumption rates (<15 g d(-1)) indicated a high carcinogenic risk that results from the consumption of rice-field loaches. The field biota-soil accumulation factor (BSAF) was calculated as a main measure of bioaccumulation potential. The comparisons of BSAF values and the results of multivariate analysis indicated that habitat-specific environmental conditions, mainly the paddy soil contamination levels and average temperature, decisively affected the bioaccumulation of organochlorine contaminants. When the influence of lipid contents was offset, M. mohoity loaches were found to have a higher potential to accumulation PCBs and OCPs than P. dabryanus loaches, while the bioaccumulation potentials did not exhibit significant differences between juvenile and adult loaches and between male and female loaches. The octanol-water partition coefficient (KOW) was the main chemical factor influencing bioaccumulation potentials. The BSAF values presented an increasing tendency with increasing log KOW values from 6.0 to approximately 7.0, followed by a decreasing tendency with a continuous increase in log KOW values. Moreover, loaches exhibited an isomeric-selective bioaccumulation for p,p'-chlorinated DDTs, alpha HCH, beta-HCH, delta-HCH and cis-chlordane. PMID- 27396616 TI - An investigation into the effects of silver nanoparticles on natural microbial communities in two freshwater sediments. AB - The expanding production and usage of commercial silver nanoparticles (AgNPs) will inevitably increase their environmental release, with sediments as a substantial sink. However, little knowledge is available about the potential impacts of AgNPs on freshwater sediment microbial communities, as well as the interactions between microbial communities and biogeochemical factors in AgNPs polluted sediment. To address these issues, two different sediments: a eutrophic freshwater sediment and an oligotrophic freshwater sediment, were exposed to 1 mg/g of either AgNO3, uncoated AgNPs (35-nm and 75-nm), or polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) (30-50 nm) for 45 days. High-throughput sequencing of 16S ribosomal ribonucleic acid (16S rRNA) genes using the Illumina MiSeq platform was conducted to evaluate the effects of Ag addition on bacterial community composition. Moreover, sediment microbial biomass and activity were assessed by counting cultivable bacterial number and determining enzyme activities. During the 45-day exposure, compared with no amendment control, some treatments had resulted in significant changes and alterations of sediment biomass or bacterial enzyme activities shortly. While the microbial components at phylum level were rarely affected by AgNPs addition, and as confirmed by the statistical analysis with two-factor analysis of similarities (ANOSIM), there were no significant differences on bacterial community structure across the amended treatments. Redundancy analysis further demonstrated that chemical parameters acid-volatile sulfide (AVS) and simultaneously extracted silver (SE-Ag) in sediment significantly structured the overall bacterial community in sediments spiked with various silver species. In summary, these findings suggested that the ecotoxicity of AgNPs may be attenuated by the transformation under complex environmental conditions and the self-adaption of sediment microbial communities. PMID- 27396617 TI - Soft-Mechanochemistry: Mechanochemistry Inspired by Nature. AB - Cells and bacteria use mechanotransduction processes to transform a mechanical force into a chemical/biochemical response. The area of chemistry where chemical reactions are induced by mechanical forces is called mechanochemistry. Over the last few years, chemists developed force-induced reactions affecting covalent bonds in molecules under tension which requires high energy input and/or high intensity forces. In contrast, in nature, mechanotransduction processes take place with forces of much weaker intensity and much less demanding energy. They are mainly based on protein conformational changes or changes in supramacromolecular architectures. Mechanochemistry based on such low-energy demanding processes and which does not affect chemical bonds can be called soft mechanochemistry. In this feature article, we first discuss some examples of soft mechanochemistry processes encountered in nature, in particular, cryptic sites, allowing us to define more precisely the concepts underlying soft mechanochemistry. A series of examples, developed over the past few years, of chemomechanoresponsive systems based on soft-mechanochemistry principles are given. We describe, in particular, cryptic site surfaces, enzymatically active films whose activity can be modulated by stretching and films where stretching induces changes in their fluorescence properties. Finally, we give our view of the future of soft-mechanochemistry. PMID- 27396618 TI - Mechanism of c-Met and EGFR tyrosine kinase inhibitor resistance through epithelial mesenchymal transition in non-small cell lung cancer. AB - According to currently available estimates from Cancer Research UK, 14.1 million new lung cancer cases were diagnosed and a staggering 8.2 million people worldwide died from lung cancer in 2012. EGFR and c-Met are two tyrosine kinase receptors most commonly overexpressed or mutated in Non-small Cell Lung Cancer (NSCLC) resulting in increased proliferation and survival of lung cancer cells. Tyrosine kinase inhibitors (TKIs), such as erlotinib, approved by the FDA as first/second line therapy for NSCLC patients have limited clinical efficacy due to acquired resistance. In this manuscript, we investigate and discuss the role of epithelial mesenchymal transition (EMT) in the development of resistance against EGFR and c-Met TKIs in NSCLC. Our findings show that Zeb-1, a transcriptional repressor of E-Cadherin, is upregulated in TKI-resistant cells causing EMT. We observed that TKI-resistant cells have increased gene and protein expression of EMT related proteins such as Vimentin, N-Cadherin, beta-Catenin and Zeb-1, while expression of E-Cadherin, an important cell adhesion molecule, was suppressed. We also confirmed that TKI-resistant cells display mesenchymal cell type morphology, and have upregulation of beta-Catenin which may regulate expression of Zeb-1, a transcriptional repressor of E-Cadherin in TKI-resistant NSCLC cells. Finally, we show that down-regulating Zeb-1 by inducing miR-200a or beta-Catenin siRNA can increase drug sensitivity of TKI-resistant cells. PMID- 27396619 TI - Rabies virus inactivates cofilin to facilitate viral budding and release. AB - Cytoplasmic actin and actin-associated proteins have been identified in RABV particles. Although actin is involved in RABV entry into cells, the specific role of actin in RABV budding and release remains unknown. Our study found that RABV M protein-mediated virion budding depends on intact actin filaments. Confocal microscopy demonstrated a block to virions budding, with a number of M protein mediated budding vesicles detained in the cell cytoplasm. Furthermore, RABV infection resulted in inactivation of cofilin and upregulation of phosphorylated cofilin. Knockdown of cofilin reduced RABV release. These results for the first time indicate that RABV infection resulted in upregulation of phosphorylated cofilin to facililtate actin polymerization for virus budding. PMID- 27396620 TI - The splicing factor SRSF1 modulates pattern formation by inhibiting transcription of tissue specific genes during embryogenesis. AB - Alternative splicing is a major mechanism regulating pattern of gene expression through the production of multiple mRNAs from a single gene transcript. Any misregulation can cause various human diseases and also have severe effects on embryogenesis. SRSF1 is one of the critical factors regulating alternative splicing at many stages of vertebrate development and any disturbance in SRSF1 leads to serious consequences. In current study, we investigated the effects of loss of the SRSF1 gene using antisense morpholino oligonucleotides (MO) in Xenopus embryogenesis. It is evident from the results of RT-PCR and whole-mount in situ hybridization that SRSF1 is a maternal gene having strong expression in head, eyes and central nervous system. Moreover, SRSF1 morphants exhibited malformed phenotypes, including miscoiled guts, heart and cartilage formation, edema in the head and heart, and small eyes. Especially, in SRSF1 morphants, bone cartilage formation was reduced in the brain and Nkx-2.5 expression was dramatically reduced in the heart of SRSF1 morphants. In addition, a dramatic reduction in functional chordin RNA in SRSF1 morphants was observed suggesting that chordin is one of the targets of SRSF1. Thus, we concluded that SRSF1 is an essential factor for pattern formation including heart, cartilage and germ layers through the regulation of specific genes. PMID- 27396621 TI - Drug repurposing of minocycline against dengue virus infection. AB - Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon alpha (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection. PMID- 27396622 TI - Down-regulation of Homer1 attenuates t-BHP-induced oxidative stress through regulating calcium homeostasis and ER stress in brain endothelial cells. AB - Endothelial dysfunction in brain endothelial cells contributes to vasogenic cerebral edema and increased mortality after various neurological diseases. The postsynaptic density protein Homer1 plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The present study investigated the role of Homer1 in modulating cell survival using an in vitro endothelial dysfunction model in murine brain endothelial cells (mBECs). Treatment with tert-butyl hydroperoxide (t-BHP) induced a dose-dependent toxicity in mBECs, with no effects on Homer1 expression and distribution. Knockdown of Homer1 using specific siRNA significantly alleviated lactate dehydrogenase (LDH) release, increased cell viability, and ultimately decreased apoptosis after t-BHP treatment. Moreover, Homer1 knockdown attenuated t-BHP-induced ROS generation, lipid peroxidation and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential (MMP), ATP synthesis collapse and mitochondrial swelling. The results of Ca(2+) imaging showed that Homer1 was involved in inositol trisphosphate receptors (IP3R)- and ryanodine receptor (RyR)-mediated intracellular Ca(2+) release, and also mediated t-BHP-induced Ca(2+) release from the endoplasmic reticulum (ER). In addition, knockdown of Homer1 significantly prevented activation of ER stress markers induced by t-BHP exposure. All these results showed that Homer1 is involved in t-BHP-induced endothelial dysfunction in mBECs, and may be an ideal candidate for searching gene intervention strategy for preventing endothelial oxidative stress in vitro. PMID- 27396623 TI - Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue. AB - Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue related diseases. PMID- 27396624 TI - A solid self-nanoemulsifying system of the BCS class IIb drug dabigatran etexilate to improve oral bioavailability. AB - AIM: To develop dabigatran etexilate (DE)-loaded self-nanoemulsifying drug delivery systems (SNEDDS) for the prevention of stroke and thromboembolism. MATERIALS & METHODS: SNEDDS were optimized by ternary phase diagrams and then further solidified into dispersible tablets. In vitro dissolution was analyzed by a phase distribution study. In situ absorption and in vivo pharmacokinetic studies were tested in male Sprague-Dawley rats. RESULTS: The phase distribution study showed that more than 60% of DE was retained in the oil phase. Dissolution rate was dramatically enhanced without significant precipitation (<30%) in simulated intestinal fluid. Optimized SNEDDS had 531.80% relative bioavailability compared with Pradaxa((r)) capsules (a commercial DE product). CONCLUSION: The developed SNEDDS are promising materials for improving the dissolution and oral bioavailability of BCS class IIb drugs. PMID- 27396626 TI - Portuguese National Registry on Cardiac Electrophysiology (2013/2014): An analysis. PMID- 27396625 TI - Homologous recombination-dependent repair of telomeric DSBs in proliferating human cells. AB - Telomeres prevent chromosome ends from being recognized as double-stranded breaks (DSBs). Meanwhile, G/C-rich repetitive telomeric DNA is susceptible to attack by DNA-damaging agents. How cells balance the need to protect DNA ends and the need to repair DNA lesions in telomeres is unknown. Here we show that telomeric DSBs are efficiently repaired in proliferating cells, but are irreparable in stress induced and replicatively senescent cells. Using the CRISPR-Cas9 technique, we specifically induce DSBs at telomeric or subtelomeric regions. We find that DSB repair (DSBR) at subtelomeres occurs in an error-prone manner resulting in small deletions, suggestive of NHEJ. However, DSBR in telomeres involves 'telomere clustering', 3'-protruding C-rich telomeric ssDNA, and HR between sister chromatid or interchromosomal telomeres. DSBR in telomeres is suppressed by deletion or inhibition of Rad51. These findings reveal proliferation-dependent DSBR in telomeres and suggest that telomeric HR, which is normally constitutively suppressed, is activated in the context of DSBR. PMID- 27396627 TI - Portuguese National Registry on Cardiac Electrophysiology, 2013 and 2014. AB - The authors present the results of the national registry of electrophysiology of the Portuguese Association for Arrhythmology, Pacing and Electrophysiology (APAPE) for 2013 and 2014. The registry is annual and voluntary, and data are collected retrospectively. Data for electrophysiological studies, ablations and cardioverter-defibrillator implantations for 2013 and 2014 are presented. Developments over the years and their implications are analyzed and discussed. PMID- 27396629 TI - REDLetr: Workflow and tools to support the migration of legacy clinical data capture systems to REDCap. AB - OBJECTIVE: A memory clinic at an academic medical center has relied on several ad hoc data capture systems including Microsoft Access and Excel for cognitive assessments over the last several years. However these solutions are challenging to maintain and limit the potential of hypothesis-driven or longitudinal research. REDCap, a secure web application based on PHP and MySQL, is a practical solution for improving data capture and organization. Here, we present a workflow and toolset to facilitate legacy data migration and real-time clinical research data collection into REDCap as well as challenges encountered. MATERIALS AND METHODS: Legacy data consisted of neuropsychological tests stored in over 4000 Excel workbooks. Functions for data extraction, norm scoring, converting to REDCap-compatible formats, accessing the REDCap API, and clinical report generation were developed and executed in Python. RESULTS: Over 400 unique data points for each workbook were migrated and integrated into our REDCap database. Moving forward, our REDCap-based system replaces the Excel-based data collection method as well as eases the integration into the standard clinical research workflow and Electronic Health Record. CONCLUSION: In the age of growing data, efficient organization and storage of clinical and research data is critical for advancing research and providing efficient patient care. We believe that the workflow and tools described in this work to promote legacy data integration as well as real time data collection into REDCap ultimately facilitate these goals. PMID- 27396630 TI - Percutaneous Closure of Paravalvular Regurgitation After Transcatheter Aortic Valve Implantation: A Systematic Review. AB - Paravalvular regurgitation (PVR) remains one of the drawbacks of transcatheter aortic valve implantation (TAVI). Details of percutaneous closure (PCC) of PVR after TAVI remain obscure. We aimed to explore the patient characteristics, procedural details, closure devices used, and outcomes of PCC after TAVI. A systematic search of the MEDLINE/PubMed and Embase databases from January 2002 to September 2015 was conducted. Reports considered to include same patient were excluded and only the studies with largest cohorts were included. A total of 14 studies including 58 patients (61 cases) were included in the study. A balloon expandable (BE) valve was used more frequently compared with a self-expandable (SE) valve (72.6% vs 27.4%, respectively). The mean success rate was 86.9% (100% and 77.8%, respectively; P = 0.097). The median number of closure devices used was 1 (range, 1-4) and did not differ between SE and BE valves (P = 0.71). Mean time from index procedure to PCC did not differ between SE and BE valves (295 +/- 380 days vs 379 +/- 353 days; P = 0.71). Seven patients had history of valve-in valve and 6 patients had procedural success. Among the patients with available follow-up data (94.8%), there were 15 deaths (27.3%). Percutaneous closure of PVR after TAVI had a high success rate in selected patients in both BE and SE valves. The success rate, timing, and number of closure devices were similar between BE and SE valves. However, prognosis remains fairly poor. PMID- 27396628 TI - Trends in primary angioplasty in Portugal from 2002 to 2013 according to the Portuguese National Registry of Interventional Cardiology. AB - INTRODUCTION AND OBJECTIVES: The aim of the present paper was to report trends in coronary angioplasty for the treatment of ST-elevation myocardial infarction (STEMI) in Portugal. METHODS: Prospective multicenter data from the Portuguese National Registry of Interventional Cardiology (RNCI) and official data from the Directorate-General for Health (DGS) were studied to analyze percutaneous coronary intervention (PCI) procedures for STEMI from 2002 to 2013. RESULTS: In 2013, 3524 primary percutaneous coronary intervention (p-PCI) procedures were performed (25% of all procedures), an increase of 315% in comparison to 2002 (16% of all interventions). Between 2002 and 2013 the rate increased from 106 to 338 p PCIs per million population per year. Rescue angioplasty decreased from 70.7% in 2002 to 2% in 2013. During this period, the use of drug-eluting stents grew from 9.9% to 69.5%. After 2008, the use of aspiration thrombectomy increased, reaching 46.7% in 2013. Glycoprotein IIb-IIIa inhibitor use decreased from 73.2% in 2002 to 23.6% in the last year of the study. Use of a radial approach increased steadily from 8.3% in 2008 to 54.6% in 2013. CONCLUSION: During the reporting period there was a three-fold increase in primary angioplasty rates per million population. Rescue angioplasty has been overtaken by p-PCI as the predominant procedure since 2006. New trends in the treatment of STEMI were observed, notably the use of drug-eluting stents and radial access as the predominant approach. PMID- 27396631 TI - Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation. AB - OBJECTIVE: The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. APPROACH: Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. MAIN RESULTS: PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. SIGNIFICANCE: Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation. PMID- 27396632 TI - Pancreatic cancer: cause for optimism? PMID- 27396633 TI - Refugee children with cancer in Turkey. PMID- 27396634 TI - Outcomes for girls without HPV vaccination in Japan. PMID- 27396635 TI - Phosphenes in patients receiving radiotherapy. PMID- 27396636 TI - Garlic: a stake through the heart of cancer? PMID- 27396637 TI - Playing Where's Wally with cancer. PMID- 27396638 TI - Adverse event development in clinical oncology trials. PMID- 27396639 TI - Adverse event development in clinical oncology trials. PMID- 27396640 TI - Adverse event development in clinical oncology trials - Authors' reply. PMID- 27396641 TI - The direct-to-consumer genetics debate. PMID- 27396642 TI - LUX-Lung 7: is there enough data for a final conclusion? PMID- 27396643 TI - LUX-Lung 7: is there enough data for a final conclusion? PMID- 27396644 TI - LUX-Lung 7: is there enough data for a final conclusion? PMID- 27396645 TI - LUX-Lung 7: is there enough data for a final conclusion? - Author's reply. PMID- 27396646 TI - Prophylactic cranial irradiation for patients with lung cancer. AB - The incidence of brain metastases in patients with lung cancer has increased as a result of improved local and systemic control and better diagnosis from advances in brain imaging. Because brain metastases are responsible for life-threatening symptoms and serious impairment of quality of life, resulting in shortened survival, prophylactic cranial irradiation has been proposed in both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) to try to improve incidence of brain metastasis, survival, and eventually quality of life. Findings from randomised controlled trials and a meta-analysis have shown that prophylactic cranial irradiation not only reduces the incidence of brain metastases in patients with SCLC and with non-metastatic NSCLC, but also improves overall survival in patients with SCLC who respond to first-line treatment. Although prophylactic cranial irradiation is potentially associated with neurocognitive decline, this risk needs to be balanced against the potential benefit in terms of brain metastases incidence and survival. Several strategies to reduce neurotoxicity are being investigated. PMID- 27396647 TI - Health-related quality of life in locally advanced and metastatic breast cancer: methodological and clinical issues in randomised controlled trials. AB - Breast cancer is the leading cause of cancer death among women worldwide, and increasingly, randomised controlled trials of this disease are measuring the health-related quality of life of these patients. In this systematic Review, we assess the adequacy of methods used to report health-related quality of life (HRQOL) from 49 eligible randomised controlled trials of advanced breast cancer. We compare our findings with those from the literature to investigate whether the standard of HRQOL reporting in this field has changed. We conclude that the overall reporting of HRQOL has improved, but some crucial aspects remain problematic, such as the absence of HRQOL research hypotheses and the overemphasis on statistical rather than clinical significance. Additionally, new challenges are arising with the emergence of novel treatments and the advent of personalised medicine, and improved HRQOL tools are required to cover the range of side-effects of newer therapies. PMID- 27396649 TI - Observation of the Sagnac Effect in the Magnetization of Magnetic Nanoparticles in Water. AB - A square optical loop used to observe the Sagnac effect was constructed by using a 632.8-nm He-Ne laser, a polarizing beam splitter and three mirrors, combined with a detection system. When a magnetic field was applied from the transversal direction to the beam of the loop, which passed through the sample cell containing magnetic nanoparticles (MNPs) in water, Sagnac interference was observed depending on the concentration of MNPs, indicating evolution of the magnetic birefringence. A possible analytical use of the magnetic Sagnac effect has been suggested. PMID- 27396648 TI - Challenges in breast and cervical cancer control in Japan. AB - Since the mid-1990s, there has been an increasing incidence of, and mortality from, cervical and breast cancers in Japan. Such an increase has raised concerns over the efficiency of Japan's screening programmes for these cancers. Although citizens benefit from universal health coverage, the Japanese health insurance system mostly focuses on tertiary prevention and disease treatment, while secondary prevention (screening) is low priority. Citizens have multiple opportunities to be screened for cancer-either through programmes organised by municipalities, or individual or collective, opportunistic and comprehensive health check-ups on a voluntary basis. Despite this, however, participation is as low as 35% of the target population for both cancers. In this Policy Review, we discuss the challenges in the prevention of breast and cervical cancers in Japan, particularly focusing on the structure of the National Health Insurance system and the National Cancer Control Plan, reasons for low participation as a result of social and political attitudes, as well as providing recommendations to overcome these challenges. Japanese women would benefit from new measures to increase participation, a national data surveillance programme to monitor screening activities, and the implementation of a quality assurance system among all providers. PMID- 27396650 TI - Detection of Organophosphorus Pesticides with Colorimetry and Computer Image Analysis. AB - Organophosphorus pesticides (OPs) represent a very important class of pesticides that are widely used in agriculture because of their relatively high-performance and moderate environmental persistence, hence the sensitive and specific detection of OPs is highly significant. Based on the inhibitory effect of acetylcholinesterase (AChE) induced by inhibitors, including OPs and carbamates, a colorimetric analysis was used for detection of OPs with computer image analysis of color density in CMYK (cyan, magenta, yellow and black) color space and non-linear modeling. The results showed that there was a gradually weakened trend of yellow intensity with the increase of the concentration of dichlorvos. The quantitative analysis of dichlorvos was achieved by Artificial Neural Network (ANN) modeling, and the results showed that the established model had a good predictive ability between training sets and predictive sets. Real cabbage samples containing dichlorvos were detected by colorimetry and gas chromatography (GC), respectively. The results showed that there was no significant difference between colorimetry and GC (P > 0.05). The experiments of accuracy, precision and repeatability revealed good performance for detection of OPs. AChE can also be inhibited by carbamates, and therefore this method has potential applications in real samples for OPs and carbamates because of high selectivity and sensitivity. PMID- 27396651 TI - SERS-active Ag Nanostars Substrates for Sensitive Detection of Ethyl Carbamate in Wine. AB - A simple and sensitive surface-enhanced Raman scattering (SERS) method for the detection of ethyl carbamate (EC) is reported in this work. Star-shaped silver nanostars (Ag NSs) were used as a novel SERS substrate. In comparison to other plasmonic nanoparticles (NPs), including Au NPs, Au NSs and Ag NPs, Ag NSs exhibit best SERS activity. Raman signal of EC at a trace level can be enhanced by several orders of magnitude with the help of Ag NSs. The Raman intensity of EC increased linearly with an increase of the EC concentration in the range from 5 * 10(-9) mol L(-1) to 1.0 * 10(-4) mol L(-1) with detection limit (LOD) of 1.37 * 10(-9) mol L(-1) (S/N = 3). The developed SERS approach also has the advantages of being simple, fast and requiring less amount of the sample. It could serve as a useful technology for the rapid determination of EC in both alcoholic beverages and fermented food. PMID- 27396652 TI - Absolute Quantification of Lipophilic Shellfish Toxins by Quantitative Nuclear Magnetic Resonance Using Removable Internal Reference Substance with SI Traceability. AB - Okadaic acid (OA), a lipophilic shellfish toxin, was accurately quantified using quantitative nuclear magnetic resonance with internal standards for the development of an authentic reference standard. Pyridine and the residual proton in methanol-d4 were used as removable internal standards to limit any contamination. They were calibrated based on a maleic acid certified reference material. Thus, the concentration of OA was traceable to the SI units through accurate quantitative NMR with an internal reference substance. Signals from the protons on the oxygenated and unsaturated carbons of OA were used for quantification. A reasonable accuracy was obtained by integrating between the lower and upper (13)C satellite signal range when more than 4 mg of OA was used. The best-determined purity was 97.4% (0.16% RSD) when 20 mg of OA was used. Dinophysistoxin-1, a methylated analog of OA having an almost identical spectrum, was also quantified by using the same methodology. PMID- 27396653 TI - Identification of Proteinaceous Binders in Ancient Tripitaka by the Use of an Enzyme-linked Immunosorbent Assay. AB - Proteinaceous materials, such as ovabumin and collagen, were commonly used as binding media, and as adhesives and protective coatings. However, the identification of ancient proteinaceous binders is a great challenge for archaeologists, due to their limited sample size, complex combinations of various ingredients and reduced availability of the binder during the process of protein degradation. In this paper, an enzyme-linked immunosorbent assay (ELISA) provides to be a particularly promising method for the detection of proteinaceous binding materials in ancient relics. The present work focused on the specific identification of proteins in archaeological binders, which was brushed on the Tripitaka. Two samples, the adhesion area (S1) and the ink area (S2), were tested by ELISA. The results showed that both S1 and S2 reacted positively when treated with an anti-collagen-I antibody. It proved the existence of proteinaceous binders in Ancient Tripitaka, and the percentage of collagen in S1 and S2 was 61.44 and 15.4%, respectively. Compared with other conventional techniques, ELISA has advantages of high specificity, sensitivity, rapidity and low cost, making it especially suitable for the protein detection in the archaeological field. PMID- 27396654 TI - Thermodynamics of Complexation between Thiourea-based Receptor and Acetate in Water/Acetonitrile Mixture. AB - A thiourea-based receptor has been extensively studied for selective anion recognition for reasons of its strong hydrogen bond donor ability. In the present study, the thermodynamics of complexation between a thiourea-based receptor and acetate was examined in a water/acetonitrile mixture. The receptor used in this study was N,N'-bis(p-nitrophenyl)thiourea (BNPTU). UV/vis spectroscopic titration and isothermal titration calorimetry (ITC) experiments clearly revealed endothermic and entropy-driven complexation of BNPTU with acetate in water/acetonitrile mixtures. Since the endothermic peaks found in water/acetonitrile mixtures were about three times greater than those in acetonitrile, it appears that preferential hydration of both receptor and acetate was responsible for the endothermic and entropy-driven complexation reaction. The thermodynamic properties found in this study have the potential to contribute to the design of a thiourea-based anion receptor. PMID- 27396655 TI - A Novel Copper(II) Sensor Based on a Unique Water-soluble Porphyrin. AB - A unique water-soluble porphyrin [5,10,15,20-tetra(3-ethoxy-4-hydroxy-5 sulfonate)phenyl porphyrin, H2TEHPPS] was designed and synthesized, which could be used as a potential sensor for the determination of Cu(2+). Studies were performed in the solution. The concentration of H2TEHPPS was 5 MUmol L(-1). The optical properties of H2TEHPPS were investigated based on the absorption spectra. The results show that the absorbance of H2TEHPPS at 417 nm is directly proportional to the concentration of Cu(2+) in the range of 0 - 2.5 MUmol L(-1). H2TEHPPS can thus be used as a novel class of Cu(2+) sensors. PMID- 27396656 TI - Sensitive Colorimetric Detection of MicroRNA Based on Target Catalyzed Double-arm Hairpin DNA Assembling. AB - The common drawbacks of the current colorimetric sensing platform using gold nanoparticles (AuNP) as an indictor is its relatively low sensitivity, which restrict their analytical application for low-level analytes, such as the detection of the microRNA (miRNA). In the present work, we developed a novel strategy to construct a colorimetric sensing platform for miRNA based on target catalyzed hairpin DNA assembling. Unlike a single-stranded DNA probe or a single arm hairpin structure DNA probe, in our strategy the double-arm hairpin structure DNA probe was first designed, and was further demonstrated to work well in catalysis the of hairpin DNA assembly reaction, which significantly enhanced the sensitivity of the AuNP based colorimetric sensing platform. In addition, compared to other miRNA detection schemes reported previously, the proposed strategy is not only enzyme-free, label-free, immobilization-free, but also eliminates the need for any sophisticated instrumentation. The proposed strategy may open a new way to allow miRNAs expression to be profiled in a decentralized setting, such as at point-of-care. PMID- 27396657 TI - Aptamer-based Resonance Light Scattering for Sensitive Detection of Acetamiprid. AB - In this work, an aptasensor-based resonance light-scattering (RLS) method was developed for the sensitive and selective detection of acetamiprid. The ABA (acetamiprid binding aptamer)-stabilized gold nanoparticles (ABA-AuNPs) were used as a probe. Highly specific single-strand DNA (ssDNA, i.e, aptamers) that bind to acetamiprid with high affinity were employed to discriminate other pesticides, such as edifenphos, kanamycin, metribuzin et. al. The sensing approach is based on a specific interaction between acetamiprid and ABA. Aggregation of AuNPs was specifically induced by the desorption of the ABA from the surface of AuNPs, which caused the RLS signal intensity to be enhanced at 700 nm. The alteration of AuNPs' aggregation has been successfully optimized by controlling several conditions. Under the optimal conditions, the RLS intensity changes (I/I0) of AuNPs were linearly correlated with the acetamiprid concentration in the range of 0 - 100 nM. The detection limit is 1.2 nM (3sigma). This method had also been used for acetamiprid detection in lake water samples. PMID- 27396658 TI - Highly Sensitive Fluorescence Methods for the Determination of Alfuzosin, Doxazosin, Terazosin and Prazosin in Pharmaceutical Formulations, Plasma and Urine. AB - Polymeric ionic liquid-coated magnetic nanoparticles have been successfully prepared as adsorbents for the magnetic solid-phase extraction of four drugs, namely alfuzosin, doxazosin, terazosin and prazosin, from pharmaceutical preparations, urine samples and plasma samples. The four drugs were detected by fluorescence spectrophotometer. Several extraction parameters, including the pH of the solution; the type, ratio and volume of the desorbing reagent; the amount of adsorbent; the time of the extraction and desorption processes; and the addition of NaCl, were investigated and optimized. Linear responses were determined for the four drugs in the concentration range of 0.5 - 45 ng mL(-1). The limit of detection values for alfuzosin, doxazosin, terazosin and prazosin, which were defined as three times the standard deviation of a blank sample, were determined to be 0.035, 0.034, 0.027 and 0.028 ng mL(-1) (n = 11), respectively. Furthermore, this new method gave preconcentration factors of 114.5, 111.3, 111.1 and 108.5 for these four drugs. PMID- 27396659 TI - A Simple and Rapid Method Based on Anti-aggregation of Silver Nanoparticles for Detection of Poly(diallyldimethylammonium chloride) in Tap Water. AB - A simple and rapid method was developed for the detection of poly(diallyldimethylammonium chloride) (PDADMAC) using citrate-capped silver nanoparticles (AgNPs). Detection was based on anti-aggregation of AgNPs in phosphate buffer caused by PDADMAC. Due to its positive charges, PDADMAC was adsorbed onto AgNPs via electrostatic interaction with citrate, which resulted in the charges at the particle surfaces to become positive and caused repulsion among particles. Furthermore, long-chain PDADMAC provided steric hindrance. These two effects promoted the dispersion of AgNPs in the phosphate buffer. A change in the state of dispersion influenced the surface plasmon resonance (SPR) of AgNPs. Therefore, in this work, the concentration of PDADMAC was determined by monitoring changes in absorbance (at 396 nm) caused by SPR of AgNPs. Under optimal conditions, the calibration was linear over the range of 1 to 100 mg L( 1) with a detection limit of 0.7 mg L(-1). Satisfactory precision was obtained (RSD = 2.8%). This method was successfully applied to the determination of PDADMAC in tap water samples. The recoveries ranged from 86.0 - 107.5%. PMID- 27396660 TI - Synchronous Multi-sits Determination of H2O2 in Vertical Water Based on Phosphor TiO2/SiO2 Nanocomposite. AB - A promising strategy for trace analysis of hydrogen peroxide (H2O2) in natural water was established based on solid substrate room temperature phosphorimetry. The use of TiO2/SiO2 composite material as a phosphor for H2O2 detection was investigated. TiO2/SiO2 nanoparticle material was manufactured into a test kit for synchronous multilevel sampling test in the water sample reservoir. The proposed TiO2/SiO2 test kit displayed a wide linear response to H2O2 concentrations ranging from 1.0 * 10(-6) to 1.0 * 10(-1) M with a detection limit of 4.6 * 10(-7) M. When the concentration of other species was 100 times of 1.0 * 10(-4) M H2O2, the proposed test kit exhibited good selectivity toward the coexistence of 20 foreign ions. Satisfactory agreement between the proposed kit and spectrophotometric method was obtained, which demonstrated the possibility of its further development into a promising commercial phosphorescence sensor. PMID- 27396661 TI - Tracing the Geographical Origin of Onions by Strontium Isotope Ratio and Strontium Content. AB - The strontium (Sr) isotope ratio ((87)Sr/(86)Sr) and Sr content were used to trace the geographical origin of onions from Japan and other countries, including China, the United States of America, New Zealand, Australia, and Thailand. The mean (87)Sr/(86)Sr ratio and Sr content (dry weight basis) for onions from Japan were 0.70751 and 4.6 mg kg(-1), respectively, and the values for onions from the other countries were 0.71199 and 12.4 mg kg(-1), respectively. Linear discriminant analysis was performed to classify onions produced in Japan from those produced in the other countries based on the Sr data. The discriminant equation derived from linear discriminant analysis was evaluated by 10-fold cross validation. As a result, the origins of 92% of onions were correctly classified between Japan and the other countries. PMID- 27396662 TI - Evaluating the Aging of Multiple Emulsions Using Resonance-Enhanced Multiphoton Ionization Time-of-Flight Mass Spectrometry. AB - Resonance-enhanced multiphoton ionization time-of-flight mass spectrometry was applied to measurements of multiple emulsions with no pretreatment; a method for the quantitative evaluation of aging was proposed. We prepared water-in-oil-in water (W/O/W) multiple emulsions containing toluene and m-phenylenediamine. The samples were measured immediately following both preparation and after having been stirred for 24 h. Time profiles of the peak areas for each analyte species were obtained, and several intense spikes for toluene could be detected from each sample after stirring, which suggests that the concentration of toluene in the middle phase had increased during stirring. On the other hand, in the case of a W/O/W multiple emulsion containing phenol and m-phenylenediamine, spikes for m phenylenediamine, rather than phenol, were detected after stirring. In the present study, the time-profile data were converted into a scatter plot in order to quantitatively evaluate the aging. As a result, the ratio of the plots where strong signal intensities of toluene were detected increased from 8.4% before stirring to 33.2% after stirring for 24 h. The present method could be a powerful tool for evaluating multiple emulsions, such as studies on the kinetics of the encapsulation and release of active ingredients. PMID- 27396663 TI - Simultaneous Electrochemical Determination of Nicotinamide Adenine Dinucleotide and Ascorbic Acid at Carbon Nanotube Electrode. AB - Simultaneous electrochemical determination of nicotinamide adenine dinucleotide (NADH) and ascorbic acid (AA) at a carbon nanotube electrode is presented. The discrimination of NADH and AA is conducted with the difference of peak potential by differential pulse voltammetry. Two well-distinguished anodic peaks, +0.56 and +0.26 V, due to NADH and AA are observed. The characteristics of those peaks were independent from each other. The attained characteristics for simultaneous determination of NADH and AA are (i) NADH measurement at the concentration range of 0.030 - 2.0 mM in the presence of 1.2 mM AA, and (ii) AA measurement at the concentration range of 0.030 - 2.0 mM in the presence of 2.0 mM NADH. PMID- 27396664 TI - Determination of the Molar Extinction Coefficients of the B800 and B850 Absorption Bands in Light-harvesting Complexes 2 Derived from Three Purple Photosynthetic Bacteria Rhodoblastus acidophilus, Rhodobacter sphaeroides, and Phaeospirillum molischianum by Extraction of Bacteriochlorophyll a. AB - The molar extinction coefficients of light-harvesting complex 2 (LH2) have been ambiguous in spite of its fame and wide utilization. Herein we determine the molar extinction coefficients of the LH2 proteins derived from the three purple photosynthetic bacteria Rhodoblastus acidophilus, Rhodobacter sphaeroides and Phaeospirillum molischianum at 298 K by direct extraction of bacteriochlorophyll (BChl) a from the lyophilized proteins, followed by estimation of BChl a amounts from their electronic absorption spectra. PMID- 27396665 TI - Shear-Driven Flow Ice Chromatography as a Possible Tool Probing Ice/Water Interface. AB - Although ice chromatography is a useful probe of ice interfaces, its low separation efficiency has often made difficult to access the ice/water interface. Coupling of this method with shear-driven flow chromatography, which has high separation potential, solves the problems involved in ice chromatography. This paper reports on shear-driven flow ice chromatographic instrumentation, and discusses the separation performance. Electrostatic separation of positively and negatively charged dyes is demonstrated with an OH(-)-doped ice plate as a stationary phase. PMID- 27396667 TI - A Herald Patch Almost Encircling the Trunk-Extreme Pityriasis Rosea Gigantea in a Young Child. AB - An 18-month-old girl presented with pityriasis rosea gigantea. The herald patch encircled almost the entire trunk. The distribution of lesions on the trunk and proximal aspects of the limbs, the collarette scaling, the orientation of some lesions along the skin crease lines, and biopsy findings substantiated the diagnosis. PMID- 27396668 TI - The Road Ahead in Education: Milestones for Geriatric Psychiatry Subspecialty Training. AB - OBJECTIVE: The Accreditation Council of Graduate Medical Education (ACGME) Milestone Project is the next step in a series of changes revamping the system of graduate medical education. In 2013 the ACGME completed the general psychiatry milestones. The ACGME then pursued creation of milestones for accredited psychiatric subspecialty fellowships. This article documents the work of the geriatric psychiatry subspecialty milestones work group. It reports the history and rationale supporting the milestones, the milestone development process, and the implications for geriatric psychiatry fellowship training. METHODS: In consultation with the American Association for Geriatric Psychiatry, the American Board of Psychiatry and Neurology, and the ACGME Psychiatry Residency Review Committee, the ACGME appointed a working group to create the geriatric psychiatry milestones using the general psychiatry milestones as a guide. CONCLUSION: The geriatric psychiatry milestones are the result of an iterative process resulting in the definition of the characteristics vital to a fellowship-trained geriatric psychiatrist. It is premature to assess their effect on psychiatric training. The true impact of the milestones will be determined as each training director uses the milestones to re-evaluate their program curriculum and the educational and clinical learning environment. The ACGME is currently collecting the information about the milestone performance of residents and fellows to further refine and determine how the milestones can best be used to assist programs in improving training. PMID- 27396669 TI - Lead uptake increases drought tolerance of wild type and transgenic poplar (Populus tremula x P. alba) overexpressing gsh 1. AB - Growth and development of plants largely depends on their adaptation ability in a changing climate. This is particularly true on heavy metal contaminated soils, but the interaction of heavy metal stress and climate on plant performance has not been intensively investigated. The aim of the present study was to elucidate if transgenic poplars (Populus tremula x P. alba) with enhanced glutathione content possess an enhanced tolerance to drought and lead (Pb) exposure (single and in combination) and if they are good candidates for phytoremediation of Pb contaminated soil. Lead exposure reduced growth and biomass accumulation only in above-ground tissue of wild type poplar, although most of lead accumulated in the roots. Drought caused a decline of the water content rather than reduced biomass production, while Pb counteracted this decline in the combined exposure. Apparently, metals such as Pb possess a protective function against drought, because they interact with abscisic acid dependent stomatal closure. Lead exposure decreased while drought increased glutathione content in leaves of both plant types. Lead accumulation was higher in the roots of transgenic plants, presumably as a result of chelation by glutathione. Water deprivation enhanced Pb accumulation in the roots, but Pb was subject to leakage out of the roots after re-watering. Transgenic plants showed better adaptation under mild drought plus Pb exposure partially due to improved glutathione synthesis. However, the transgenic plants cannot be considered as a good candidate for phytoremediation of Pb, due to its small translocation to the shoots and its leakage out of the roots upon re-watering. PMID- 27396670 TI - The Fourier analysis applied to the relationship between (7)Be activity in the Serbian atmosphere and meteorological parameters. AB - Air sample monitoring in Serbia, Belgrade started in the 1960s, while (7)Be activity in air and total (dry and wet) deposition has been monitored for the last 22 years by the Environment and Radiation Protection Department of the Institute for Nuclear Sciences, Vinca. Using this data collection, the changes of the (7)Be activity in the air and the total (wet and dry) deposition samples, as well as their correlation with meteorological parameters (temperature, pressure, cloudiness, sunshine duration, precipitation and humidity) that affect (7)Be concentration in the atmosphere, were mathematically described using the Fourier analysis. Fourier analysis confirmed the expected; the frequency with the largest intensity in the harmonic spectra of the (7)Be activity corresponds to a period of 1 year, the same as the largest intensity frequency in Fourier series of meteorological parameters. To analyze the quality of the results produced by the Fourier analysis, we compared the measured values of the parameters with the values calculated according to the Fourier series. Absolute deviations between measured and predicted mean monthly values are in range from 0.02 mBq/m(3) to 0.7 mBq/m(3) for (7)Be activity in air, and 0.01 Bq/m(2) and 0.6 Bq/m(2) for (7)Be activity in deposition samples. Relatively good agreement of measured and predicted results offers the possibility of prediction of the (7)Be activity. PMID- 27396671 TI - Increase in ozone due to the use of biodiesel fuel rather than diesel fuel. AB - The consumption of fuel by vehicles emits nitrogen oxides (NOx) and non-methane hydrocarbons (NMHCs) into the atmosphere, which are important ozone precursors. Ozone is formed as a secondary pollutant via photochemical processes and is not emitted directly into the atmosphere. In this paper, the ozone increase resulting from the use of biodiesel and diesel fuels was investigated, and the different ozone formation trends were experimentally evaluated. Known amounts of exhaust gas from a power generator operated using biodiesel and diesel fuels were added to ambient air. The quality of the ambient air, such as the initial NMHC and NOx concentrations, and the irradiation intensity have an effect on the ozone levels. When 30 cm(3) of biodiesel fuel exhaust gas (BFEG) or diesel fuel exhausted gas (DFEG) was added to 18 dm(3) of ambient air, the highest ratios of ozone increase from BFEG compared with DFEG in Japan and Vietnam were 31.2 and 42.8%, respectively, and the maximum ozone increases resulting from DFEG and BFEG compared with the ambient air in Japan were 17.4 and 26.4 ppb, respectively. The ozone increase resulting from the use of BFEG was large and significant compared to that from DFEG under all experimental conditions. The ozone concentration increased as the amount of added exhaust gas increased. The ozone increase from the Jatropha-BFEG was slightly higher than that from waste cooking oil-BFEG. PMID- 27396672 TI - Intra-operative micro-electrode recording in functional neurosurgery: Past, present, future. AB - The field of functional neurosurgery has experienced a rise, fall and lastly a renaissance over the past 75years. Micro-electrode recording (MER) played a key role during this eventful journey. However, as the intra-operative MRI continues to evolve, a pertinent question about the utility of MER has been raised in recent years. In this article, we critically review these current controversies. The English literature is reviewed and the complex technique of MER is discussed in a simplified manner. The improvement of neuroimaging and its application in functional neurosurgery, especially in deep brain stimulation, is discussed. Finally, the current controversies and technical advances which can direct the future are reviewed. The results of existing meta-analyses addressing the controversies are summarized. Wide variations of pre-operative and intra operative targeting methods have been described in the literature. Though functional neurosurgery is generally safe, complications do occur and multiple passes during MER can certainly add to the risk of inadvertent hemorrhage and infection. Additionally, the recent introduction of newer MRI modalities has ensured better delineation of the target. However, MER is still useful to address brain shift, for mapping of newer targets, for ablative surgeries and in centers without an intra-operative imaging facility. In the current scenario, it is nearly impossible to conduct a prospective study to decide the utility of MER. The importance of MER may further diminish in the future as a routine procedure, but its role as a gold standard procedure may still persist. PMID- 27396673 TI - Investigation of sperm telomere length as a potential marker of paternal genome integrity and semen quality. AB - Recent studies have reported shorter sperm telomere length (STL) in men with idiopathic infertility. The aim of this study was to measure STL in semen samples from men to evaluate whether STL variation is associated with chromosomal abnormality, DNA fragmentation, traditional semen parameters, IVF outcome, or all four factors. A significant correlation between telomere length and diploidy was observed (P = 0.037). Additionally, STL was found to be positively associated with sperm count (P = 0.006); oligospermic samples had particularly short telomeres (0.9 +/- 0.1 versus 1.4 +/- 0.1; P = 0.0019). The results confirmed a link between sperm DNA fragmentation and aneuploidy, previously proposed (P = 0.009). A negative relationship was demonstrated between sperm concentration and aneuploidy and Sperm DNA framentation (P = 0.03, P < 0.0001, respectively). For a subset of 51 of the 73 sperm samples used for fertilization, IVF outcomes were known. A total of 17.6% of these samples had atypical STLs. None of these samples produced an ongoing pregnancy. In contrast, the pregnancy rate for samples that had STLs in the normal range was 35.7% (P = 0.044). In conclusion, STL has potential as a fast and inexpensive form of sperm quality assessment. PMID- 27396674 TI - Early differential sensitivity of evoked-potentials to local and global shape during the perception of three-dimensional objects. AB - Here we investigated the time course underlying differential processing of local and global shape information during the perception of complex three-dimensional (3D) objects. Observers made shape matching judgments about pairs of sequentially presented multi-part novel objects. Event-related potentials (ERPs) were used to measure perceptual sensitivity to 3D shape differences in terms of local part structure and global shape configuration - based on predictions derived from hierarchical structural description models of object recognition. There were three types of different object trials in which stimulus pairs (1) shared local parts but differed in global shape configuration; (2) contained different local parts but shared global configuration or (3) shared neither local parts nor global configuration. Analyses of the ERP data showed differential amplitude modulation as a function of shape similarity as early as the N1 component between 146-215ms post-stimulus onset. These negative amplitude deflections were more similar between objects sharing global shape configuration than local part structure. Differentiation among all stimulus types was reflected in N2 amplitude modulations between 276-330ms. sLORETA inverse solutions showed stronger involvement of left occipitotemporal areas during the N1 for object discrimination weighted towards local part structure. The results suggest that the perception of 3D object shape involves parallel processing of information at local and global scales. This processing is characterised by relatively slow derivation of 'fine-grained' local shape structure, and fast derivation of 'coarse-grained' global shape configuration. We propose that the rapid early derivation of global shape attributes underlies the observed patterns of N1 amplitude modulations. PMID- 27396676 TI - WFH 2016 World Congress Abstracts, Orlando, Florida, USA, July 24-28, 2016. PMID- 27396675 TI - Tracking the intrusion of unwanted memories into awareness with event-related potentials. AB - Involuntary retrieval of unwanted memories is a common symptom in several clinical disorders, including post-traumatic stress disorder. With an aim to track the temporal dynamics of such memory intrusions, we recorded electrophysiological measures of brain activity while participants engaged in a Think/No-Think task. We presented the left hand word (the cue) of previously encoded word pairs in green or red font. We asked participants to think of the associated right hand word (the associate) when the cue appeared in green (Think condition) and to avoid thinking of the associate when the cue appeared in red (No-Think condition). To isolate cases when participants experienced an intrusive memory, at the end of each trial, participants judged whether the response had come to mind; we classified memories that came to mind during No-Think trials, despite efforts to stop retrieval, as intrusions. In an event-related potential (ERP) analysis, we observed a negative going slow wave (NSW) effect that indexed the duration of a trace in mnemonic awareness; whereas voluntary retrieval and maintenance of the associate was related to a sustained NSW that lasted throughout the 3-s recording epoch, memory intrusions generated short-lived NSWs that were rapidly truncated. Based on these findings, we hypothesize that the intrusion-NSW reflects the associate briefly penetrating working memory. More broadly, these findings exploit the high temporal resolution of ERPs to track the online dynamics of memory intrusions. PMID- 27396677 TI - Antibacterial chitosan/silk sericin 3D porous scaffolds as a wound dressing material. AB - Antimicrobial mixed dressings have traditionally been used to minimize bacterial infection of burns and other wounds. This study presents the advancement of biocompatible chitosan/silk sericin (CHT/SS) scaffolds combined with lauric acid (LA) and zinc oxide nanoparticles (nZnO) for the successful wound dressing applications. Antibacterial assay results showed that the diameters of the inhibition zone increased from 2 +/- 0.4 to 7 +/- 0.1 mm for Escherichia coli, as well as from 2.5 +/- 0.2 to 6 +/- 0.4 mm for Staphylococcus aureus while CHTS/SS/100nZnO compared to CHT/SS/0.01LA. The results not only showed excellent inhibition against Gram-positive and Gram-negative bacterial growth but also revealed improved proliferation and extended viability for HaCaT cells. PMID- 27396678 TI - Development of a duplex real-time RT-PCR for the simultaneous detection and differentiation of Theiler's murine encephalomyelitis virus and rat theilovirus. AB - Theiler's murine encephalomyelitis virus (TMEV) and rat theilovirus (RTV), the member of the genus Cardiovirus, are widespread in laboratory mice and rats, and are potential contaminants of biological materials. Cardioviruses infection may cause serious complications in biomedical research. To improve the efficiency of routine screening for Cardioviruses infection, a duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed for simultaneous detection and differentiation of TMEV and RTV. The duplex assay was specific for reference strains of TMEV and RTV, and no cross-reaction was found with seven other rodent viruses. The limits of detection of both TMEV and RTV were 4*10(1) copies RNA/reaction. Reproducibility was estimated using standard dilutions, with coefficients of variation <3.1%. 439 clinical samples were evaluated by both duplex real-time RT-PCR and conventional RT-PCR. For 439 clinical samples,95 samples were positive for TMEV and 72 samples were positive for RTV using duplex real-time RT-PCR approach, whereas only 77 samples were positive for TMEV and 66 samples were positive for RTV when conventional RT-PCR was applied. Mixed infections were found in 20 samples when analyzed by conventional RT-PCR whereas 30 samples were found to be mixed infection when duplex real-time RT-PCR was applied. This duplex assay provides a useful tool for routine health monitoring and screening of contaminated biological materials of these two viruses. PMID- 27396679 TI - Preface to: "microRNAs in lipid/energy metabolism and cardiometabolic disease". PMID- 27396681 TI - Energy and time modelling of kerbside waste collection: Changes incurred when adding source separated food waste. AB - The collection of source separated kerbside municipal FW (SSFW) is being incentivised in Australia, however such a collection is likely to increase the fuel and time a collection truck fleet requires. Therefore, waste managers need to determine whether the incentives outweigh the cost. With literature scarcely describing the magnitude of increase, and local parameters playing a crucial role in accurately modelling kerbside collection; this paper develops a new general mathematical model that predicts the energy and time requirements of a collection regime whilst incorporating the unique variables of different jurisdictions. The model, Municipal solid waste collect (MSW-Collect), is validated and shown to be more accurate at predicting fuel consumption and trucks required than other common collection models. When predicting changes incurred for five different SSFW collection scenarios, results show that SSFW scenarios require an increase in fuel ranging from 1.38% to 57.59%. There is also a need for additional trucks across most SSFW scenarios tested. All SSFW scenarios are ranked and analysed in regards to fuel consumption; sensitivity analysis is conducted to test key assumptions. PMID- 27396680 TI - Eosinophilia-Associated Coronary Artery Vasospasm in Patients with Aspirin Exacerbated Respiratory Disease. AB - BACKGROUND: Some patients with aspirin-exacerbated respiratory disease (AERD) and eosinophilia report angina-type chest pain that occurs at rest and responds to corticosteroid therapy. The frequency of eosinophilia-associated coronary artery vasospasm in patients with AERD, a disease characterized by blood and respiratory tissue eosinophilia, however, is unknown. OBJECTIVE: The objective of this study was to understand the cause of the chest pain described above and determine the most appropriate treatment for it. METHODS: A chart review of 153 patients with AERD who are followed at Brigham and Women's Hospital was performed. Patients who reported any type of chest pain were assessed for the presence of cardiac risk factors, eosinophilia, and response of chest pain to a variety of treatments. Two patients with AERD and eosinophilia who had recurrent chest pain due to suspected vasospasm are described in detail, and 8 other cases are also summarized. RESULTS: Of the 153 patients reviewed, 10 had a history of chest pain concerning for ischemia. Of the 10 patients with chest pain, 8 had undergone aspirin desensitization and initiated high-dose aspirin therapy; of these, 6 reported an increase in the frequency or severity of chest pain while on high-dose aspirin with improvement after aspirin discontinuation or dose reduction. Many patients had traditional cardiac risk factors, but none had any evidence of coronary atherosclerosis; almost all had significant eosinophilia. Their chest pain did not improve with typical antianginal treatments but did respond to corticosteroid therapy. CONCLUSIONS: Although uncommon, patients with AERD can develop eosinophilia-associated coronary artery vasospasm, which is occasionally worsened by high-dose aspirin. Patients with AERD who present with symptoms of ischemic chest pain should be screened for eosinophilia, as early treatment with corticosteroids can be life-saving. PMID- 27396682 TI - Horse manure as feedstock for anaerobic digestion. AB - Horse keeping is of great economic, social and environmental benefit for society, but causes environmental impacts throughout the whole chain from feed production to manure treatment. According to national statistics, the number of horses in Sweden is continually increasing and is currently approximately 360,000. This in turn leads to increasing amounts of horse manure that have to be managed and treated. Current practices could cause local and global environmental impacts due to poor performance or lack of proper management. Horse manure with its content of nutrients and organic material can however contribute to fertilisation of arable land and recovery of renewable energy following anaerobic digestion. At present anaerobic digestion of horse manure is not a common treatment. In this paper the potential for producing biogas and biofertiliser from horse manure is analysed based on a thorough literature review in combination with mathematical modelling and simulations. Anaerobic digestion was chosen as it has a high degree of resource conservation, both in terms of energy (biogas) and nutrients (digestate). Important factors regarding manure characteristics and operating factors in the biogas plant are identified. Two crucial factors are the type and amount of bedding material used, which has strong implications for feedstock characteristics, and the type of digestion method applied (dry or wet process). Straw and waste paper are identified as the best materials in an energy point of view. While the specific methane yield decreases with a high amount of bedding, the bedding material still makes a positive contribution to the energy balance. Thermophilic digestion increases the methane generation rate and yield, compared with mesophilic digestion, but the total effect is negligible. PMID- 27396683 TI - Comparison of 3 Handling Techniques for Endoscopically Obtained Gastric and Duodenal Biopsy Specimens: A Prospective Study in Dogs and Cats. AB - BACKGROUND: Limited evidence exists in the literature regarding whether a specific mount is preferable to use for processing endoscopically obtained gastrointestinal biopsy specimens. HYPOTHESIS/OBJECTIVES: To compare 3 methods of handling endoscopically obtained gastrointestinal biopsy specimens from collection to laboratory processing and to determine if any technique produced superior results. ANIMALS: Twenty-three dogs and cats presented for gastrointestinal signs. METHODS: Prospective study of dogs and cats presented with gastrointestinal signs to a veterinary teaching referral hospital which underwent upper gastrointestinal endoscopy. Biopsy specimens were taken from the stomach and duodenum and submitted to the laboratory using 3 techniques: mounted on a cucumber slice, mounted on a moisturized synthetic foam sponge, and floating free in formalin. The techniques were compared with regard to the specimens' width, orientation, presence of artifacts, and pathologist's confidence in diagnosis. RESULTS: Twenty-three patients were included, with a total of 528 biopsies collected. Specimens on cucumber slice and on sponge were significantly wider (P < .001 and P = .001, respectively) compared to those floating free in formalin (mean width of 3.81 versus 3.31 and 2.52 mm, respectively). However, specimens on synthetic sponge had significantly fewer artifacts compared to those on cucumber slice (P = .05) and those floating free in formalin (P = .02). Confidence in the diagnosis also was superior with the sponge technique over floating free specimens (P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE: The use of mounted gastrointestinal biopsy specimens was superior over the use of specimens floating free in formalin. This technique improved the quality of the specimens and the pathologist's confidence in their histopathologic interpretation. PMID- 27396684 TI - Oxa-Pictet-Spengler reaction as key step in the synthesis of novel sigma receptor ligands with 2-benzopyran structure. AB - The Oxa-Pictet-Spengler reaction of methyl 3-hydroxy-4-phenylbutanoate (8) was explored to obtain novel sigma receptor ligands. 1-Acyl protected piperidone ketals 10 and 11 reacted with phenylethanol 8 to yield spirocyclic compounds. Aliphatic aldehyde acetals 19 provided 1,3-disubstituted 2-benzopyrans 20 with high cis-diastereoselectivity. The intramolecular Oxa-Pictet-Spengler reaction of 24 led to the tricyclic compound 25. The spirocyclic compounds 18 show high sigma1 affinity (Ki 20-26nM) and sigma1/sigma2 selectivity (>9-fold), when a large substituent (n-octyl, benzyl, phenylpropyl) is attached to the piperidine N atom. Opening of the piperidine ring to yield aminoethyl (22, 23) or aminomethyl derivatives (21) resulted in reduced sigma1 affinity and sigma1/sigma2 selectivity. PMID- 27396685 TI - Design, synthesis and biological evaluation of N-methyl-N-[(1,2,3-triazol-4 yl)alkyl]propargylamines as novel monoamine oxidase B inhibitors. AB - Different azides and alkynes have been coupled via Cu-catalyzed 1,3-dipolar Huisgen cycloaddition to afford a novel family of N1- and C5-substituted 1,2,3 triazole derivatives that feature the propargylamine group typical of irreversible MAO-B inhibitors at the C4-side chain of the triazole ring. All the synthesized compounds were evaluated against human MAO-A and MAO-B. Structure activity relationships and molecular modeling were utilized to gain insight into the structural and chemical features that enhance the binding affinity and selectivity between the two enzyme isoforms. Several lead compounds, in terms of potency (submicromolar to low micromolar range), MAO-B selective recognition, and brain permeability, were identified. One of these leads (MAO-B IC50 of 3.54MUM, selectivity MAO-A/MAO-B index of 27.7) was further subjected to reversibility and time-dependence inhibition studies, which disclosed a slow and irreversible inhibition of human MAO-B. Overall, the results support the suitability of the 4 triazolylalkyl propargylamine scaffold for exploring the design of multipotent anti-Alzheimer compounds endowed with irreversible MAO-B inhibitory activity. PMID- 27396687 TI - Mechanisms involved in the in vitro contractile dysfunction induced by different concentrations of ferrous iron in the rat myocardium. AB - Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2+)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2+) 100-1000MUM. The contractile response to Ca(2+) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2+) whereas O2(-) was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2+) influx were impaired only by Fe(2+) 1000MUM, and antioxidants had no effect. In skinned fibers, Fe(2+) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2+) sensitivity. These effects are mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000MUM, Fe(2+) appears to depress force also by reducing Ca(2+) influx, probably due to a competition at Ca(2+) channels. PMID- 27396686 TI - Intracellular and extracellular microRNA: An update on localization and biological role. AB - MicroRNA (miRNA) is a class of small non-coding RNAs which mediate post transcriptional gene silencing (PTGS) by sequence-specific inhibition of target mRNAs translation and/or lowering their half-lives in the cytoplasm. Together with their binding partners, Argonaute (AGO) proteins, miRNAs form cores of RNA induced silencing complexes (RISC). Despite a substantial progress in understanding RISC structure, until recently little was known about its localization in the cell. This review is aimed to provide an overview of the emerging picture of miRNA and RISC localization and function both in the intracellular space and outside of the cell. In contrast to the common assumption that PTGS occurs in the cytoplasm, it was found to operate mainly on the membranes of the endoplasmic reticulum (ER). Besides ER membranes miRNAs were found in all main cellular compartments including nucleus, nucleolus and mitochondria where they regulate various processes including transcription, translation, alternative splicing and DNA repair. Moreover, a certain pool of miRNAs may not be associated with RISC and carry completely different functions. Finally, the discovery of cell-free miRNAs in all biological fluids suggests that miRNAs might also act as signaling molecules outside the cell, and may be utilized as biomarkers for a variety of diseases. In this review we discuss miRNA secretion mechanisms and possible pathways of cell-cell communication via miRNA containing exosomes in vivo. PMID- 27396688 TI - A decrease in cellular microRNA-27a content is involved in azacytidine-induced P glycoprotein expression in SKM-1 cells. AB - We established an azacytidine (AzaC)-resistant human acute myeloid leukemia (AML) cell line (SKM-1/AzaC) by culturing SKM-1 cells in the presence of increasing amounts of AzaC for six months. Because AzaC is not a substrate of P-glycoprotein (a product of the ABCB1 gene; ABCB1), ABCB1 was not responsible for AzaC resistance; nevertheless, it was notably upregulated in SKM-1/AzaC cells. In addition, the transcription of the Nfkb1 gene, which encodes a member of the canonical NF-kappaB regulatory pathway, was downregulated, and the transcription of the Nfkb2 gene, which encodes a member of the non-canonical NF-kappaB regulatory pathway, was upregulated in SKM-1/AzaC cells. Here, we investigate whether miRNA-27a and miRNA-138 (both of which are known to be regulators of ABCB1 expression) are involved in the regulation of ABCB1 expression in SKM 1/AzaC cells. We observed decreased levels of miRNA-27a but of not miRNA-138 in SKM-1/AzaC cells compared with SKM-1 cells. The transfection of SKM-1/AzaC cells with a miRNA-27a mimic induced the downregulation of the ABCB1 mRNA. This was associated with an increase in Nfkb1 and a decrease in Nfkb2 transcript levels in SKM-1/AzaC cells. Taken together, these data indicate that the downregulation of miRNA-27a is involved in the upregulation of ABCB1 expression in SKM-1/AzaC cells, and this effect is associated with a switch between the canonical and non canonical NF-kappaB pathways. PMID- 27396689 TI - Surface-enhanced Raman scattering activities of carbon nanotubes decorated with silver nanoparticles. AB - We synthesized a carbon nanotube (CNT) loaded with silver nanoparticles (AgNPs) composite as an effective surface enhanced Raman scattering (SERS) substrate via a low-cost, simple citrate reduction method. The hybrid materials were confirmed by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), ultraviolet-visible (UV-vis) spectrophotometer and Raman spectroscopy. Rhodamine 6G (R6G) was used as the probe analyte. The experimental results indicated that the detection concentration level was down to 10(-14) M. Additionally, we discussed the uniformity by conducting SERS position mapping within an area of 5 MUm * 5 MUm; meanwhile, we performed time-course SERS mapping experiments to study the evaporation process of probe molecules of the prepared samples. Finally, we simulated the electromagnetic field distribution based on SEM images (obtained the ratio of surface area to the area of silver particles) by the finite difference time domain (FDTD) method. PMID- 27396690 TI - Bulk heterojunction organic photovoltaics from water-processable nanomaterials and their facile fabrication approaches. AB - Organic thin film photovoltaics based on bulk-heterojunction donor-acceptor combinations have received significant interest due to their potential for low cost, large-scale solution processing. However, current state-of-the-art cells utilise materials soluble mainly in halogenated solvents which pose processing challenges due to their toxicity and thus environmental hazards. In this contribution, we look at various nanomaterials, and alternative processing of these solar cells using environmentally friendly solvents, and review recently reported different strategies and approaches that are making inroads in this field. Specifically, we focus on the use of water-dispersible donors and acceptors, use of aqueous solvents for fabrication and discuss the merits of the two main approaches of water-processable solar cells; namely, through the use of water-soluble materials and the use of aqueous dispersion rather than a solution, as well as review some of the recent advances in alternative fabrication techniques. PMID- 27396691 TI - Use of Historical Surgical Times to Predict Duration of Primary Total Knee Arthroplasty. AB - BACKGROUND: Primary total knee arthroplasty (TKA) is one of the most commonly performed procedures at US hospitals. Surgeons are typically asked to estimate surgical control time (SCT) needed for the procedure. Here, we compare the performance of a surgeon's prediction against a potentially more accurate method of using historical averages over the last 3, 5, 10, and 20 cases. METHODS: Data were collected on all scheduled primary TKAs done at one institution from October 2008 to September 2014. For each case, actual SCT (aSCT) and predicted SCT were obtained. Historical SCTs were calculated based on the mean of the last 3, 5, 10, and 20 aSCTs of the same surgeon. Estimation biases were calculated based on the difference between aSCT and predicted SCT or between aSCT and historical estimates. Values were compared using Kruskal-Wallis analysis of variance and Steel-Dwass pairwise comparisons. RESULTS: A total of 2539 primary TKAs were evaluated across 9 surgeons. Surgeons overestimated SCT by an average of 18.1 minutes. Using 3-20 cases in the historical average reduced mean estimation bias to a range of -0.1 to -0.3 minutes (P < .001). None of the historical estimations were significantly different from each other, demonstrating a lack of improvement with additional cases (P < .001). CONCLUSION: Historical averages of procedure times appear to be a promising method of estimating surgical time for primary TKAs. Here, we show that even a small number of cases (eg, 3) can reduce estimation biases compared to solely using surgeons' estimates alone. PMID- 27396692 TI - Melatonin antagonizes cadmium-induced neurotoxicity by activating the transcription factor EB-dependent autophagy-lysosome machinery in mouse neuroblastoma cells. AB - Cadmium (Cd), a highly ubiquitous heavy metal, induces neurotoxicity. Melatonin, a major secretory product of the pineal gland, protects against Cd-induced neurotoxicity. However, the mechanism that accounts for this protection remains to be elucidated. Herein, we exposed mouse neuroblastoma cells (Neuro-2a cells) to different concentrations of cadmium chloride (CdCl2 ) (12.5, 25, and 50 MU mol L(-1) ) for 24 hours. We showed that Cd inhibits autophagosome-lysosome fusion and impairs lysosomal function, subsequently leading to nerve cell death. In addition, Cd decreases the level of transcription factor EB (TFEB) but induces the nuclear translocation of TFEB, associated with compromised lysosomal function or a compensatory effect after the impairment of the autophagic flux. Moreover, compared to the 50-MU mol L(-1) Cd group, administration of 1 MU mol L(-1) melatonin increased "TFEB-responsive genes" (P<.05) and the levels of lysosomal associated membrane protein (0.57+/-0.06 vs 1.00+/-0.11, P<.05), preserved lysosomal protease activity (0.52+/-0.01 vs 0.90+/-0.02, P<.05), maintained the lysosomal pH level (0.50+/-0.01 vs 0.87+/-0.05, P<.01), and enhanced autophagosome-lysosome fusion (0.05+/-0.00 vs 0.21+/-0.01, P<.01). Notably, melatonin enhanced TFEB expression (0.37+/-0.04 vs 0.72+/-0.07, P<.05) and nuclear translocation (2.81+/-0.08 vs 3.82+/-0.05, P<.05). Tfeb siRNA blocked the melatonin-mediated elevation in autophagy-lysosome machinery in Cd-induced neurotoxicity (P<.01). Taken together, these results uncover a potent role for TFEB-mediated autophagy in the pathogenesis of Cd-induced neurotoxicity, suggesting that control of the autophagic pathway by melatonin might provide an important clue for exploring potential targets for novel therapeutics of Cd induced neurotoxicity. PMID- 27396694 TI - PET Imaging of Extracellular pH in Tumors with (64)Cu- and (18)F-Labeled pHLIP Peptides: A Structure-Activity Optimization Study. AB - pH (low) insertion peptides (pHLIP peptides) target acidic extracellular environments in vivo due to pH-dependent cellular membrane insertion. Two variants (Var3 and Var7) and wild-type (WT) pHLIP peptides have shown promise for in vivo imaging of breast cancer. Two positron emitting radionuclides ((64)Cu and (18)F) were used to label the NOTA- and NO2A-derivatized Var3, Var7, and WT peptides for in vivo biodistribution studies in 4T1 orthotopic tumor-bearing BALB/c mice. All of the constructs were radiolabeled with (64)Cu or [(18)F]-AlF in good yield. The in vivo biodistribution of the 12 constructs in 4T1 orthotopic allografted female BALB/c mice indicated that NO2A-cysVar3, radiolabeled with either (18)F (4T1 uptake; 8.9 +/- 1.7%ID/g at 4 h p.i.) or (64)Cu (4T1 uptake; 8.2 +/- 0.9%ID/g at 4 h p.i. and 19.2 +/- 1.8% ID/g at 24 h p.i.), shows the most promise for clinical translation. Additional studies to investigate other tumor models (melanoma, prostate, and brain tumor models) indicated the universality of tumor targeting of these tracers. From this study, future clinical translation will focus on (18)F- or (64)Cu-labeled NO2A-cysVar3. PMID- 27396693 TI - Role of the abdominal vagus and hindbrain in inhalational anesthesia-induced vomiting. AB - The incidence of postoperative nausea and vomiting (PONV) can be as high as 80% in patients with risk factors (e.g., females, history of motion sickness). PONV delays postoperative recovery and costs several hundred million dollars annually. Cell-based assays show that halogenated ethers (e.g., isoflurane) activate 5-HT3 receptors, which are found on gastrointestinal vagal afferents and in the hindbrain - key pathways for producing nausea and vomiting. This project evaluated the role of the vagus and activation of the hindbrain in isoflurane induced emesis in musk shrews, a small animal model with a vomiting reflex, which is lacking in rats and mice. Sham-operated and abdominal vagotomized shrews were exposed to 1 to 3% isoflurane to determine effects on emesis; vagotomy was confirmed by lack of vagal transport of the neuronal tracer Fluoro-Gold. In an additional study, shrews were exposed to isoflurane and hindbrain c-Fos was measured at 90min after exposure using immunohistochemistry. There were no statistically significant effects of vagotomy on isoflurane-induced emesis compared to sham-operated controls. Isoflurane exposure produced a significant increase in c-Fos-positive cells in the nucleus of the solitary tract and vestibular nuclei but not in the area postrema or dorsal motor nucleus. These results indicate that the abdominal vagus plays no role in isoflurane-induced emesis and suggest that isoflurane activates emesis by action on the hindbrain, as shown by c-Fos labeling. Ultimately, knowledge of the mechanisms of inhalational anesthesia-induced PONV could lead to more targeted therapies to control PONV. PMID- 27396696 TI - Biogenic manganese oxides as reservoirs of organic carbon and proteins in terrestrial and marine environments. AB - Manganese (Mn) oxides participate in a range of interactions with organic carbon (OC) that can lead to either carbon degradation or preservation. Here, we examine the abundance and composition of OC associated with biogenic and environmental Mn oxides to elucidate the role of Mn oxides as a reservoir for carbon and their potential for selective partitioning of particular carbon species. Mn oxides precipitated in natural brackish waters and by Mn(II)-oxidizing marine bacteria and terrestrial fungi harbor considerable levels of organic carbon (4.1-17.0 mol OC per kg mineral) compared to ferromanganese cave deposits which contain 1-2 orders of magnitude lower OC. Spectroscopic analyses indicate that the chemical composition of Mn oxide-associated OC from microbial cultures is homogeneous with bacterial Mn oxides hosting primarily proteinaceous carbon and fungal Mn oxides containing both protein- and lipopolysaccharide-like carbon. The bacterial Mn oxide-hosted proteins are involved in both Mn(II) oxidation and metal binding by these bacterial species and could be involved in the mineral nucleation process as well. By comparison, the composition of OC associated with Mn oxides formed in natural settings (brackish waters and particularly in cave ferromanganese rock coatings) is more spatially and chemically heterogeneous. Cave Mn oxide associated organic material is enriched in aliphatic C, which together with the lower carbon concentrations, points to more extensive microbial or mineral processing of carbon in this system relative to the other systems examined in this study, and as would be expected in oligotrophic cave environments. This study highlights Mn oxides as a reservoir for carbon in varied environments. The presence and in some cases dominance of proteinaceous carbon within the biogenic and natural Mn oxides may contribute to preferential preservation of proteins in sediments and dominance of protein-dependent metabolisms in the subsurface biosphere. PMID- 27396695 TI - The impact of adherence to inhaled drugs on 5-year survival in COPD patients: a time dependent approach. AB - PURPOSE: Whether inhaled medications improve long-term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5-year survival in COPD. METHODS: A population-based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006-2009 were enrolled. Inhaled drug daily use during 5-year follow-up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time-dependent exposure were identified: (i) long-acting beta2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio-demographic, comorbidities, drug use) and time-dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed. RESULTS: A total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow-up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43-1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79 0.99). CONCLUSIONS: These findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate-severe COPD patients. (c) 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. PMID- 27396697 TI - Young Ischemic Stroke in Association with Ovarian Hyperstimulation Syndrome. AB - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially fatal complication of medical ovarian stimulation. Uncommonly, it is associated with thromboembolic complications with venous thrombosis being more common than arterial thromboembolic events. We present a case of cerebral infarction in the setting of severe OHSS secondary to in vitro fertilization treatment with no residual neurological deficits. MATERIALS AND METHODS: We also performed a review of previously published ischemic cerebral infarction and cerebral venous sinus thrombosis (CVST) cases associated with OHSS to evaluate common patterns in presentations, commonly affected central nervous system sites, trends for therapeutic options in these cases, and outcomes. CONCLUSION: We have included 27 cases of ischemic cerebral infarction and 7 cases of CVST previously published in English literature. We have included cases of central retinal artery occlusion in the ischemic cerebral infarction group, and central retinal vein occlusion in the CVST group. Mean ages of presentation were 31 +/- 4.84 and 34 +/- 4.90 years for ischemic cerebral infarction and CVST, respectively. Ischemic strokes commonly affect large cortical areas with unilateral weakness, aphasia, unilateral sensory changes, and visual field deficits being the common presentations. Middle cerebral artery (n = 7) is the common site of vascular occlusion where vascular imaging has been reported, followed by internal carotid artery occlusion (n = 5). OHSS cannot be considered a direct risk for pathogenesis, but OHSS is frequently associated with hyperviscosity, which may add to the risk factors. PMID- 27396698 TI - Age does not affect complications and overall survival rate after pancreaticoduodenectomy: Single-center experience and systematic review of literature. AB - We aimed to evaluate the feasibility of pancreaticoduodenectomy (PD) in elderly patients. We retrospectively analyzed data from 206 patients who underwent PD between 2008 and 2015. The patients were divided into two groups: patients aged < 70 years (n = 117) and those aged >= 70 years (n = 89). To update the outcome of PD in elderly patients, we performed a systematic review of published work. The preoperative patient characteristics were similar between the two groups except for hypertension, which was significantly more frequent in the older group (25% vs. 52%; p < 0.001). There was no difference in the mortality (0% vs. 1%; p = 0.43) or morbidity (26% vs. 20%; p = 0.41) rates between the two groups. The overall survival rate in patients with pancreatic cancer between the two groups did not differ (p = 0.40). Twenty-one studies, including our own, were identified in the published work. The overall median morbidity and mortality rates of the elderly patients were 41.5% (range, 20-78%) and 5.8% (range, 0-10.5%), respectively. PD is feasible in elderly patients with acceptable morbidity and mortality rates. PMID- 27396699 TI - Dialysis: A wearable dialysis device: the first step to continuous therapy. PMID- 27396700 TI - Hypertension: Salt: flawed research should not divert actions to reduce intake. PMID- 27396701 TI - Coming in postgraduate medicine. PMID- 27396702 TI - From the Editor-in-Chief. PMID- 27396703 TI - Editor's mail. PMID- 27396704 TI - Problems/Solutions. PMID- 27396705 TI - What's Happening in Medicine! PMID- 27396706 TI - Washington Report on Health. PMID- 27396707 TI - Nuclear Medicine. PMID- 27396709 TI - 58th Interstate postgraduate medical assembly program. PMID- 27396711 TI - Standardized terminology and nomenclature for respiratory cytology: The Papanicolaou Society of Cytopathology guidelines. PMID- 27396712 TI - Double-decker bis(tetradiazepinoporphyrazinato) rare earth complexes: crucial role of intramolecular hydrogen bonding. AB - A series of homoleptic bis{tetrakis(5,7-bis(4-tert-butylphenyl)-6H-1,4 diazepino)[2,3-b,g,l,q]porphyrazinato}lanthanide sandwich complexes [(tBuPh)DzPz]2Ln (Ln = Lu, Er, Dy, Eu, Nd, Ce, La) were prepared and their physicochemical properties were studied to gain insight into the nature of specific interactions in diazepinoporphyrazines. The effect of annulated diazepine moieties and the Ln ionic radius on the properties of the complexes was investigated in comparison with double-decker phthalocyanines. A combination of experimental and theoretical studies revealed the presence of two types of hydrogen bonding interactions in the metal-free porphyrazine and the corresponding sandwich complexes, namely, interligand C-H(ax)N(meso) hydrogen bonding and O-HN(Dz) ligand-water interaction. The interligand hydrogen bonding imparts high stability of the ligand dimer and the double-decker compounds in a reduced state. This work is the first comprehensive investigation into the fundamental understanding of the unusual properties of diazepine-containing macroheterocycles. PMID- 27396713 TI - One-Pot Conversion of Carbohydrates into Furan Derivatives via Furfural and 5 Hydroxylmethylfurfural as Intermediates. AB - Recently, there has been growing interest in the transformation of renewable biomass into value-added fuels and chemicals. The catalytic conversion of naturally abundant carbohydrates can generate two-important furan chemicals: 5 hydroxymethylfurfural (HMF) from C6 carbohydrates and furfural from C5 carbohydrates. Both HMF and furfural have received great interest as precursors in the synthesis of commodity chemicals and liquid fuels. In recent years, a trend has emerged to integrate sequential catalytic processes involving multistep reactions for the direct one-pot transformation of carbohydrates into the aimed fuels and chemicals. One-pot reactions have remarkably unique and environmentally friendly benefits, including the fact that isolation and purification of intermediate compounds can be avoided. Herein, the present article aims to review recent advances in the one-pot conversion of carbohydrates into furan derivatives via furfural and HMF as intermediates. Special attention will be paid to the catalytic systems, mechanistic insight, reaction pathways, and catalyst stability. It is expected that this review will guide researchers to develop effective catalytic systems for the one-pot transformation of carbohydrates into furan derivatives. PMID- 27396714 TI - Climate change and habitat conversion favour the same species. AB - Land-use change and climate change are driving a global biodiversity crisis. Yet, how species' responses to climate change are correlated with their responses to land-use change is poorly understood. Here, we assess the linkages between climate and land-use change on birds in Neotropical forest and agriculture. Across > 300 species, we show that affiliation with drier climates is associated with an ability to persist in and colonise agriculture. Further, species shift their habitat use along a precipitation gradient: species prefer forest in drier regions, but use agriculture more in wetter zones. Finally, forest-dependent species that avoid agriculture are most likely to experience decreases in habitable range size if current drying trends in the Neotropics continue as predicted. This linkage suggests a synergy between the primary drivers of biodiversity loss. Because they favour the same species, climate and land-use change will likely homogenise biodiversity more severely than otherwise anticipated. PMID- 27396715 TI - Ovulatory disorders are an independent risk factor for pregnancy complications in women receiving assisted reproduction treatments. AB - BACKGROUND: Conception using assisted reproduction treatments (ART) has been associated with an increased risk of pregnancy complications. It is uncertain if this is caused by ART directly, or is an association of the underlying factors causing infertility. AIMS: We assessed the relationship between assisted conception (AC) and maternal or fetal complications in a large retrospective cohort study. In a nested cohort of women receiving infertility treatment, we determined if such risk rests predominantly with certain causes of infertility. MATERIALS AND METHODS: Retrospective database analysis of 50 381 women delivering a singleton pregnancy in four public hospital obstetric units in western Sydney, and a nested cohort of 508 women receiving ART at a single fertility centre, in whom the cause of infertility was known. RESULTS: A total of 1727 pregnancies followed AC; 48 654 were spontaneous conceptions. Adjusted for age, body mass index and smoking, AC was associated with increased risk of preterm delivery (OR 1.73, 95% CI 1.50-2.02), hypertension (OR 1.55, 95% CI 1.34-1.82) and diabetes (OR 1.51, 95% CI 1.30-1.75). In the nested cohort, ovulatory dysfunction was present in 145 women and 336 had infertility despite normal ovulatory function. Ovulatory dysfunction was associated with increased risk of diabetes (OR 2.94, 95% CI 1.72-5.02) and hypertension (OR 2.40, 95% CI 1.15-5.00) compared to women with normal ovulatory function. CONCLUSIONS: Assisted conception is associated with increased risk of pregnancy complications. This risk appears greatest for women whose underlying infertility involves ovulatory dysfunction. Such disorders probably predispose towards diabetes and hypertension, which is then exacerbated by pregnancy. PMID- 27396716 TI - Transparency and reproducibility in evolutionary research. PMID- 27396718 TI - Band-Tail Transport of CuSCN: Origin of Hole Extraction Enhancement in Organic Photovoltaics. AB - Copper thiocyanate (CuSCN) is known as a promising hole transport layer in organic photovoltaics (OPVs) due to its good hole conduction and exciton blocking abilities with high transparency. Despite its successful device applications, the origin of its hole extraction enhancement in OPVs has not yet been understood. Here, we investigated the electronic structure of CuSCN and the energy level alignment at the poly(3-hexylthiophene-2,5-diyl) (P3HT)/CuSCN/ITO interfaces using ultraviolet photoelectron spectroscopy. The band-tail states of CuSCN close to the Fermi level (EF) were observed at 0.25 eV below the EF, leading to good hole transport. The CuSCN interlayer significantly reduces the hole transport barrier between ITO and P3HT due to its high work function and band-tail states. The barrier reduction leads to enhanced current density-voltage characteristics of hole-dominated devices. These results provide the origin of hole-extraction enhancement by CuSCN and insights for further application. PMID- 27396717 TI - Epigenetic silencing of TIMP4 in heart failure. AB - Tissue inhibitor of matrix metalloprotease 4 (TIMP4) is endogenously one of the key modulators of matrix metalloprotease 9 (MMP9) and we have reported earlier that cardiac specific TIMP4 instigates contractility and helps in differentiation of cardiac progenitor cells. Although studies show that the expression of TIMP4 goes down in heart failure but the mechanism is unknown. This study aims to determine the mechanism of silencing of TIMP4 in heart failure progression created by aorta-vena cava (AV) fistula. We hypothesize that there is epigenetic silencing of TIMP4 in heart failure. To validate this hypothesis, we created heart failure model by creating AV fistula in C57BL/6 mice and looked into the promoter methylation (methylation specific PCR, high resolution melting, methylation sensitive restriction enzyme and Na bisulphite treatment followed by sequencing), histone modification (ChIP assay) and microRNAs that regulate TIMP4 (mir122a) and MMP9 (mir29b and mir455-5p). The physiological parameters in terms of cardiac function after AV fistula were assessed by echocardiography. We observed that there are 7 CpG islands in the TIMP4 promoter which get methylated during the progression of heart failure which leads to its epigenetic silencing. In addition, the up-regulated levels of mir122a in part, contribute to regulation of TIMP4. Consequently, MMP9 gets up-regulated and leads to cardiac remodeling. This is a novel report to explain the epigenetic silencing of TIMP4 in heart failure. PMID- 27396719 TI - Solutions for ecosystem-level protection of ocean systems under climate change. AB - The Paris Conference of Parties (COP21) agreement renewed momentum for action against climate change, creating the space for solutions for conservation of the ocean addressing two of its largest threats: climate change and ocean acidification (CCOA). Recent arguments that ocean policies disregard a mature conservation research field and that protected areas cannot address climate change may be oversimplistic at this time when dynamic solutions for the management of changing oceans are needed. We propose a novel approach, based on spatial meta-analysis of climate impact models, to improve the positioning of marine protected areas to limit CCOA impacts. We do this by estimating the vulnerability of ocean ecosystems to CCOA in a spatially explicit manner and then co-mapping human activities such as the placement of renewable energy developments and the distribution of marine protected areas. We test this approach in the NE Atlantic considering also how CCOA impacts the base of the food web which supports protected species, an aspect often neglected in conservation studies. We found that, in this case, current regional conservation plans protect areas with low ecosystem-level vulnerability to CCOA, but disregard how species may redistribute to new, suitable and productive habitats. Under current plans, these areas remain open to commercial extraction and other uses. Here, and worldwide, ocean conservation strategies under CCOA must recognize the long-term importance of these habitat refuges, and studies such as this one are needed to identify them. Protecting these areas creates adaptive, climate-ready and ecosystem-level policy options for conservation, suitable for changing oceans. PMID- 27396720 TI - Quantification of protein biomarkers in tissues: new capabilities with pellet digestion peptide immunoaffinity LC-MS/MS. PMID- 27396722 TI - Response to comments regarding article, "Wnt5a inhibited human trophoblast cell line HTR8/SVneo invasion: implications for early placentation and preeclampsia". PMID- 27396723 TI - Surveillance for Ventilator-Associated Pneumonia: Can We Apply Centers for Disease Control and Prevention-National Healthcare Safety Network 2013 Definitions for All Settings? PMID- 27396724 TI - International Wound Journal impact factor increases year on year. PMID- 27396727 TI - Subchronic Immunotoxicity Assessment of Genetically Modified Virus-Resistant Papaya in Rats. AB - Papaya is an important fruit that provides a variety of vitamins with nutritional value and also holds some pharmacological properties, including immunomodulation. Genetically modified (GM) papaya plants resistant to Papaya ringspot virus (PRSV) infection have been generated by cloning the coat protein gene of the PRSV which can be used as a valuable strategy to fight PRSV infection and to increase papaya production. In order to assess the safety of GM papaya as a food, this subchronic study was conducted to assess the immunomodulatory responses of the GM papaya line 823-2210, when compared with its parent plant of non-GM papaya, Tainung-2 (TN-2), in Sprague-Dawley (SD) rats. Both non-GM and GM 823-2210 papaya fruits at low (1 g/kg bw) and high (2 g/kg bw) dosages were administered via daily oral gavage to male and female rats consecutively for 90 days. Immunophenotyping, mitogen-induced splenic cell proliferation, antigen-specific antibody response, and histopathology of the spleen and thymus were evaluated at the end of the experiment. Results of immunotoxicity assays revealed no consistent difference between rats fed for 90 days with GM 823-2210 papaya fruits, as opposed to those fed non-GM TN-2 papaya fruits, suggesting that with regard to immunomodulatory responses, GM 823-2210 papaya fruits maintain substantial equivalence to fruits of their non-GM TN-2 parent. PMID- 27396728 TI - Electrochemical redox-based tuning of near infrared localized plasmons of CuS nanoplates. AB - Fast and reversible control of the plasmonic properties of compound nanoparticles (i.e. CuS nanoplates) was achieved through electrochemical redox reactions. Their electrochemical tunability can be applied to fast-switching near infrared electrochromic devices, whose visible appearance is not changed by switching. PMID- 27396729 TI - Antibody-independent identification of bovine milk-derived peptides in breast milk. AB - Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow's milk allergy. However, the definite characterization of dietary cow's milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. Herein, we aimed at assessing possible CMP-derived peptides in breast milk. Using high performance liquid chromatography (HPLC)-high resolution mass spectrometry (MS), we compared the peptide fraction of breast milk from 12 donors, among which 6 drank a cup of milk daily and 6 were on a strict dairy-free diet. We identified two bovine beta lactoglobulin (beta-Lg, 2 out 6 samples) and one alphas1-casein (1 out 6 samples) fragments in breast milk from mothers receiving a cup of bovine milk daily. These CMP-derived fragments, namely beta-Lg (f42-54), (f42-57) and alphas1-casein (f180 197), were absent in milk from mothers on dairy-free diet. In contrast, neither intact nor hydrolyzed beta-Lg was detected by western blot and competitive ELISA in any breast milk sample. Eight additional bovine milk-derived peptides identified by software-assisted MS were most likely false positive. The results of this study demonstrate that CMP-derived peptides rather than intact CMP may sensitize or elicit allergic responses in the neonate through mother's milk. Immunologically active peptides from the maternal diet could be involved in priming the newborn's immune system, driving a tolerogenic response. PMID- 27396730 TI - Treatment of Multifocal Renal Cell Carcinoma in a Solitary Kidney With Nivolumab. PMID- 27396731 TI - Synthesis, Biological Evaluation and Molecular Docking of New Benzenesulfonylhydrazone as Potential anti-Trypanosoma cruzi Agents. AB - BACKGROUND: Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. METHODS: Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. RESULTS: Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 uM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 uM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. CONCLUSION: Benzenesulfonyl and N propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound. PMID- 27396733 TI - Mountain Child: Systematic Literature Review. AB - Objectives This systematic review identifies and reviews both peer-reviewed and 'grey' literature, across a range of disciplines and from diverse sources, relating to the condition of children living in mountain communities in low- and middle-income countries. Findings The literature on poverty in these communities does not generally focus on the particular vulnerabilities of children or the impact of intersecting vulnerabilities on the most marginalised members of communities. However, this literature does contribute analyses of the broader context and variety of factors impacting on human development in mountainous areas. The literature on other areas of children's lives-health, nutrition, child mortality, education, and child labour-focuses more specifically on children's particular vulnerabilities or experiences. However, it sometimes lacks the broader analysis of the many interrelated characteristics of a mountainous environment which impact on children's situations. Themes Nevertheless, certain themes recur across many disciplines and types of literature, and point to some general conclusions: mountain poverty is influenced by the very local specificities of the physical environment; mountain communities are often politically and economically marginalised, particularly for the most vulnerable within these communities, including children; and mountain communities themselves are an important locus for challenging and interrupting cycles of increasing inequality and disadvantage. While this broad-scale review represents a modest first step, its findings provide the basis for further investigation. PMID- 27396734 TI - Involvements of Trp23 in the Chitin-binding and of Trp131 in the Chitinase Activity of Rye Seed Chitinase-a. AB - The oxidation of the tryptophan residues of rye seed chitinase-a (RSC-a) and its isolated catalytic (Cat) domain by N-bromosuccinimide (NBS) was investigated in the absence and presence of oligomers of N-acetylglucosamine (GlcNAc)n. Based on the reactivity toward NBS at pH 5.9, the seven tryptophan residues present in RSC a are grouped into highly reactive (HR-), low reactive (LR-), and unreactive residues. Analyses of the peptides from 1 tryptophan- and 3 tryptophan-oxidized RSC-a showed that the HR-residue is Trp23 and the LR-residues are Trp131 and Trp141. The chitin-binding ability of RSC-a was lost upon the NBS oxidation of Trp23 at pH 5.9 or pH 7.0. This oxidation was prevented by (GlcNAc)3, which induced a high UV-difference spectrum with maxima at 284 and 293 nm. On the other hand, the chitinase activity of the Cat domain was greatly reduced by the NBS oxidation of Trp131 and Trp141 at pH 5.9, while in the NBS oxidation at pH 6.4, approximately one tryptophan residue was oxidized and about half of the activity was retained. The NBS oxidation of the isolated Cat domain at pH 5.9 was protected by (GlcNAc)4, which induced a UV-difference spectrum with maxima at 284 nm and 293 nm as well as a small trough around 300 nm, similar to that observed in RSC-c. From these results and the previous result that Trp72 in RSC-c is involved in the substrate-binding, it was suggested that Trp23 is highly exposed on the surface of the RSC-a molecule and involved in the chitin-binding, while Trp131 is involved in substrate-binding in its enzyme action. PMID- 27396732 TI - Discovery of New Anti-Schistosomal Hits by Integration of QSAR-Based Virtual Screening and High Content Screening. AB - Schistosomiasis is a debilitating neglected tropical disease, caused by flatworms of Schistosoma genus. The treatment relies on a single drug, praziquantel (PZQ), making the discovery of new compounds extremely urgent. In this work, we integrated QSAR-based virtual screening (VS) of Schistosoma mansoni thioredoxin glutathione reductase (SmTGR) inhibitors and high content screening (HCS) aiming to discover new antischistosomal agents. Initially, binary QSAR models for inhibition of SmTGR were developed and validated using the Organization for Economic Co-operation and Development (OECD) guidance. Using these models, we prioritized 29 compounds for further testing in two HCS platforms based on image analysis of assay plates. Among them, 2-[2-(3-methyl-4-nitro-5 isoxazolyl)vinyl]pyridine and 2-(benzylsulfonyl)-1,3-benzothiazole, two compounds representing new chemical scaffolds have activity against schistosomula and adult worms at low micromolar concentrations and therefore represent promising antischistosomal hits for further hit-to-lead optimization. PMID- 27396735 TI - Dielectric Relaxation of Aqueous Solution with Low-molecular-weight Nonelectrolytes and Its Relationship with Solution Structure. AB - Dielectric relaxation of water molecules was measured in the frequency range from 0.2 to 20 GHz for aqueous solutions of urea, formamide, alcohols, and saccharides. The relaxation behavior was described well by the Debye equation with a single relaxation process in most cases. The static permittivity of solution and relaxation time of water in solution changed linearly with solute concentration. The relaxation time shift of water molecules through the existence of solute was correlated well to the first virial coefficient of the activity coefficient of water suggesting the close relationship between dielectric relaxation time and aqueous solution structure. PMID- 27396736 TI - Isolation of Taka-amylase A Peptides Required for Substrate Binding. AB - An alpha-amylase from Aspergillus oryzae, Taka-amylase A (TAA), was cleaved into peptide fragments by an acid protease. Inactivation of TAA was greatly retarded by the addition of alpha-cyclodextrin or Ca(2+). TAA peptide fragments were separated into two groups having no and high affinity to the substrate, soluble starch. This separation was done by the forced affinity chromatography method by a column of epichlorohydrin cross-linked soluble starch gel. Three peptides were isolated from the high-affinity fragments, purified by the ODS-120T column, and their amino acids were sequenced. Peptides I, II, and III originated from alpha2 helix, alpha3-helix, and beta2-sheet, respectively, and all of these were located in the (beta/alpha)8 barrel of the main domain of TAA molecule. A stereo graphic view showed that Peptides I-III were at the cleft near the catalytic site. Occurrence of a Trp residue in all three peptides strongly suggested that Trp was very important in the binding of TAA to the substrate, soluble starch. PMID- 27396737 TI - Nigrosporins A and B, New Phytotoxic and Antibacterial Metabolites Produced by a Fungus Nigrospora oryzae. AB - Nigrosporin A and B, two new phytotoxic and antibacterial metabolites were isolated from a culture filtrate of Nigrospora oryzae. The active principles were absorbed on XAD-2 resin and purified by successive ODS-HPLC. The structures were identified by spectroscopic and derivatization analysis as naphthoquinone derivatives. The substances showed phytotoxic activities, such as root elongation inhibition, necrotic effects, oxygen evolution inhibition, starch synthesis inhibition, and CO2 fixation inhibition at concentrations of 10-100 ppm. They also showed growth inhibition activity against Bacillus subtilis in a disc diffusion assay as well as when compared with streptomycin. PMID- 27396738 TI - Degree of Polymerization of Cellulose from Acetobacter xylinum BPR2001 Decreased by Cellulase Produced by the Strain. AB - Acetobacter xylinum produces both cellulase and bacterial cellulose, but some report believed that this cellulase activity does not decrease the degree of polymerization (DP) of bacterial cellulose during cultivation. A. xylinum subsp. sucrofermentans BPR2001 produces two enzymes that hydrolyze CM-cellulose and cellotriose, respectively. We examined the effect of the two cellulase activities on the DP of bacterial cellulose when bacterial cells were cultured with agitation at pH 4, where little cellulase is produced, and at pH 5, where much cellulase is produced. The weight-average degree of polymerization (DPw) of bacterial cellulose remained in the range of 14,000 of 16,000 during cultivation at pH 4, but at pH 5, the DPw decreased from 16,800 to 11,000. The mechanical strength of a sheet prepared from the bacterial cellulose produced at pH 4 was higher than those of BC produced at pH 5. These results suggest that the two cellulase activities cause the decrease in DP and deterioration of physical properties of bacterial cellulose seen during cultivation. PMID- 27396739 TI - Synthesis, Biological Activity, and Metabolism of 8',8',8'-Trideuteroabscisic Acid. AB - An 8',8',8'-trideuterated analog of abscisic acid (ABA) was diastereoselectively synthesized as a new analog of ABA that is resistant to 8'-hydroxyIation, the first metabolic reaction of ABA, owing to the primary kinetic isotope effect. (+) 8',8',8'-Trideutero-ABA showed long-term activity in the rice elongation assay. The rate of metabolism of this analog in rice cell suspension culture was about two fold slower than that of (+)-ABA. The concentration of 8',8'-dideuterophaseic acid produced was about 1/3 that of phaseic acid converted from (+)-ABA. This result indicated that the long-lasting activity of the (+)-trideutero-ABA in the rice assay was the result of the delayed 8'-hydroxylation as expected. PMID- 27396740 TI - Purification and Characterization of Cystine Lyase a from Broccoli Inflorescence. AB - One of the three isoforms of an enzyme degrading L-cystine was purified to homogeneity from broccoli (Brassica oleracea var. italica) inflorescences, with use of a sensitive assay based on derivatization of a reaction product with monobromobimane. The reaction product with a thiol group was found to be thiocysteine from results of liquid chromatography-mass spectrometry and high resolution mass spectrometry. Pyruvate was also a reaction product, formed in equimolar amounts. The purified enzyme catalyzed beta-elimination of L-cystine to yield thiocysteine, pyruvate and possibly ammonia, so it was cystine lyase a. L Cystine but not D-cystine was a substrate of the enzyme. S-Methyl L-cysteine sulfoxide and S-ethyl L-cysteine sulfoxide were substrates but were less suitable than L-cystine. L- and D-cysteine and also cystathionine were not substrates. The purified enzyme (Mr 186,000) was composed of four identical subunits (Mr 45,000) and was pyridoxal 5'-phosphate-dependent. PMID- 27396741 TI - Effects of Plant Growth Regulators on Shoot Growth and Flowering of a Perennia Paddy Weed, Sagittaria pygmaea Miq. AB - Plant growth regulators (PGRs) including gibberellins (GAs) were examined for their effects on shoot growth and flowering of a perennial paddy weed, Sagittaria pygmaea Miq. Among PGRs tested, only GAs (A1 A3, A4, and A5), AC-94377 [1-(4 chloro-1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)cyclohexanecarbox-amide] and 2,6 diisopropylphenoxyacetic acid (DIPA) promoted both shoot growth and flowering. Structural requirements of GAs for promotion of flowering seemed to be different from those for shoot growth of the weed. In addition, since the course of flowering induced by DIPA was clearly different from that observed in plots treated with GA3 or AC-94377, different mechanisms may be involved in promotion of flowering. PMID- 27396742 TI - (E)-2-(4'-Methyl-3'-pentenylidene)-4-butanolide, Named beta-Acariolide: A New Monoterpene Lactone from the Mold Mite, Tyrophagus putrescentiae (Acarina: Acaridae). AB - Reinwestigation of the opisthonotal gland secretion of the mold mite, Tyrophagus putrescentiae, resulted in the isolation of a new monoterpene lactone, whose chemical structure was elucidated as (E)-2-(4'-methyl-3'-pentenylidene)-4 butanolide (3), to which we gave the trivial name beta-acariolide in relation to beta-acaridial {1, (E)-2-(4-methyl-3-pentenylidene)-butanedial}. The compound was synthesized by LiAlH3 (OEt) reduction of 1 and subsequent oxidation involving simultaneous cyclization by using Ag2CO3 on Celite. Both the E- and Z-isomers of beta-acariolide (3 and 4) were also prepared by the reaction of alpha-ethoxaly gamma-butyrolactone (6) and 4-methyl-3-pentenal under basic conditions. Their NMR spectra were compared with each other, and the geometry of the pentenylidene double bond of the isolated compound was concluded as being E. PMID- 27396743 TI - New Acylated Anthocyanins from Brassica campestris var. chinensis. AB - Two new acylated anthocyanins were isolated from beninabana, Brassica campestris var. chinensis, in addition to two known anthocyanins. The structures were established by spectral analyses. PMID- 27396744 TI - Manufacturing High Purity Maltose and Maltotetraose from Starch by a Novel and Efficient Procedure Named "Reducing End Modification Method". AB - A novel and efficient procedure named "reducing end modification method" was developed for manufacturing high purity maltooligosaccharides. By the method, high purity maltose and maltotetraose were prepared from starch. Starch was liquefied, debranched, and oxidized with sodium hypochlorite at the reducing end. The reaction mixture was treated with beta-amylase or maltotetraose-forming amylase from Pseudomonas stutzeri IFO-3773, resulting in the production of high purity maltose or maltotetraose, oxidized maltooligosaccharides, and oxidized undigested dextrin. High purity maltose (maltose content, 99.9%) or maltotetraose (maltotetraose content, 95%) was obtained very effectively from the reaction mixture by chromatography on a strong acid cation exchange resin (Na (+)). PMID- 27396745 TI - Two-mode Analysis by High-performance Liquid Chromatography of rho-Aminobenzoic Ethyl Ester-derivatized Monosaccharides. AB - rho-Aminobenzoic ethyl ester (ABEE)-derivatized monosaccharides were separated by HPLC with a trifluoroacetic acid (TFA) solution or borate buffer as the eluent. In the case of the TFA solution, ABEE-derivatized monosaccharides of the neutral and amino sugars found in animal glycoproteins were separated in a simultaneous analysis. In the case of the borate buffer, ABEE-derivatized monosaccharides of identical molecular weights such as ABEE-Gal, -Glc, and -Man were separated as stereoisomers. Glucuronic acid and galacturonic acid were detected and separated within 8 min. The relationship between the peak areas and the amounts of ABEE derivatized monosaccharides was linear in the range of 1 to 1000 pmol. PMID- 27396746 TI - 111 years of Brownian motion. AB - We consider the Brownian motion of a particle and present a tutorial review over the last 111 years since Einstein's paper in 1905. We describe Einstein's model, Langevin's model and the hydrodynamic models, with increasing sophistication on the hydrodynamic interactions between the particle and the fluid. In recent years, the effects of interfaces on the nearby Brownian motion have been the focus of several investigations. We summarize various results and discuss some of the controversies associated with new findings about the changes in Brownian motion induced by the interface. PMID- 27396747 TI - Ethical and methodological issues in research with Sami experiencing disability. AB - BACKGROUND: A study of disability among the indigenous Sami people in Norway presented a number of ethical and methodological challenges rarely addressed in the literature. OBJECTIVES: The main study was designed to examine and understand the everyday life, transitions between life stages and democratic participation of Norwegian Sami people experiencing disability. Hence, the purpose of this article is to increase the understanding of possible ethical and methodological issues in research within this field. The article describes and discusses ethical and methodological issues that arose when conducting our study and identifies some strategies for addressing issues like these. METHODS: The ethical and methodological issues addressed in the article are based on a qualitative study among indigenous Norwegian Sami people experiencing disability. The data in this study were collected through 31 semi-structured in-depth interviews with altogether 24 Sami people experiencing disability and 13 next of kin of Sami people experiencing disability (8 mothers, 2 fathers, 2 sister and 1 guardian). FINDINGS AND DISCUSSION: The researchers identified 4 main areas of ethical and methodological issues. We present these issues chronologically as they emerged in the research process: 1) concept of knowledge when designing the study, 2) gaining access, 3) data collection and 4) analysis and accountability. CONCLUSION: The knowledge generated from this study has the potential to benefit future health research, specifically of Norwegian Sami people experiencing disability, as well as health research concerning indigenous people in general, providing scientific-based insight into important ethical and methodological issues in research with indigenous people experiencing disability. PMID- 27396748 TI - Expectancy influences on attention to threat are only weak and transient: Behavioral and physiological evidence. AB - Can prior expectancies shape attention to threat? To answer this question, we manipulated the expectancies of spider phobics and nonfearful controls regarding the appearance of spider and bird targets in a visual search task. We observed robust evidence for expectancy influences on attention to birds, reflected in error rates, reaction times, pupil diameter, and heart rate (HR). We found no solid effect, however, of the same expectancies on attention to spiders; only HR revealed a weak and transient impact of prior expectancies on the orientation of attention to threat. Moreover, these asymmetric effects for spiders versus birds were observed in both phobics and controls. Our results are thus consistent with the notion of a threat detection mechanism that is only partially permeable to current expectancies, thereby increasing chances of survival in situations that are mistakenly perceived as safe. PMID- 27396749 TI - Temperament differentially influences early information processing in men and women: Preliminary electrophysiological evidence of attentional biases in healthy individuals. AB - Preferential processing of threat-related information is a robust finding in anxiety disorders. The observation that attentional biases are also present in healthy individuals suggests factors other than clinical symptoms to play a role. Using a dot-probe paradigm while event-related potentials were recorded in 59 healthy adults, we investigated whether temperament and gender, both related to individual variation in anxiety levels, influence attentional processing. All participants showed protective attentional biases in terms of enhanced attention engagement with positive information, indexed by larger N1 amplitudes in positive compared to negative conditions. Taking gender differences into account, we observed that women showed enhanced attention engagement with negative compared to neutral information, indicated by larger P2 amplitudes in congruent than in incongruent negative conditions. Attentional processing was influenced by the temperament traits negative affect and effortful control. Our results emphasize that gender and temperament modulate attentional biases in healthy adults. PMID- 27396750 TI - Individual differences in the time course of reward processing: Stage-specific links with depression and impulsivity. AB - Reward dysfunction has been implicated in a wide range of psychological disorders, including internalizing and externalizing psychopathology. Basic neuroscience research has shown that reward is a multistage process, yet it is unclear how specific stages relate to individual differences in reward sensitivity. The current study utilized event-related potentials elicited during a monetary incentive task to parse sub-stages within anticipatory and consummatory reward processing. Effects of depressive symptoms and trait impulsivity were examined at each sub-stage (N=92). Reward anticipation modulated neural activity across three sub-stages: cue detection (cue-P3), approach behavior (contingent negative variation, CNV), and outcome anticipation (stimulus preceding negativity). Reward delivery modulated activity across two sub-stages: initial evaluation (reward positivity, RewP), and allocation of attention (feedback-P3). Sensation seeking predicted faster reaction times, as well as cue P3 and RewP amplitudes. Depression and lack of premeditation interacted to predict CNV and RewP amplitudes. Results demonstrate that individual differences in reward functioning are stage-specific. PMID- 27396751 TI - Study of Protein Amyloid-Like Aggregates by Solid-State Circular Dichroism Spectroscopy. AB - Protein aggregation and amyloidogenesis are closely associated with the pathogenesis of neurodegenerative diseases. Elucidating the morphology and structure of the amyloid aggregates or fibrils is important for understanding the molecular mechanisms of these proteinopathies. This review article describes the general principle and establishment of solid-state circular dichroism (ssCD) spectroscopy, and discusses its application for the analysis of secondary structures of proteins or peptides in amyloids and structural transformation of these proteins or peptides during their amyloidogenic aggregation. PMID- 27396752 TI - Association of circulating total bilirubin with the metabolic syndrome and type 2 diabetes: A systematic review and meta-analysis of observational evidence. AB - OBJECTIVE: Emerging evidence suggests that bilirubin levels might be associated with the metabolic syndrome (MetS) and type 2 diabetes (T2D), although the nature of the association remains unclear. DESIGN: This systematic review and meta analysis investigated the relationship between total plasma bilirubin and the risk of MetS and T2D. DATA SOURCES: Relevant studies were identified using five databases (Embase, Medline [Ovid], Web of Science, PubMed, Cochrane Central and Google Scholar), with the last search done on 21 October 2015. Study references were checked and authors contacted to identify additional studies. STUDY SELECTION: Randomized controlled trials, and cohort, case-control and cross sectional studies of adults examining the association between blood bilirubin levels and MetS and T2D were included, irrespective of language and date of publication. Abstract and full-text selection was done by two independent reviewers, with a third reviewer available in case of disagreement. DATA EXTRACTION: Data were extracted by two independent reviewers using a predesigned data collection form. MAIN OUTCOMES AND MEASURES: MetS and T2D. METHODS: Summary estimates were obtained by random-effects meta-analysis. RESULTS: Of the 2313 searched references, 16 observational studies (11 cross-sectional, two prospective, one that was both cross-sectional and prospective, two retrospective and one national survey) met our inclusion criteria. Overall, data were available for 175,911 non-overlapping participants, including 7414 MetS cases and 9406 T2D cases. In the meta-analysis of seven cross-sectional studies, the pooled odds ratio (95% confidence interval) for MetS in a comparison of extreme tertiles of serum bilirubin levels was 0.70 (95% CI: 0.62, 0.78), whereas no significant association was found for the pooled estimated relative risk between two prospective studies (0.57, 95% CI: 0.11, 2.94). The corresponding estimate was 0.77 (95% CI: 0.67, 0.87) for T2D from four cross-sectional studies. CONCLUSION: The available evidence, mainly from cross-sectional studies, supports an inverse association of bilirubin levels with adverse metabolic outcomes. Large-scale prospective studies are now needed to establish whether bilirubin levels may be useful in the prevention of MetS and T2D. PMID- 27396754 TI - Shaping Tumor Microenvironment for Improving Nanoparticle Delivery. AB - BACKGROUND: Tumor microenvironment is so complex that involves in many factors of tumor. Although enhanced permeability and retention effect is a main driving force of tumor targeted nanoparticles, the tumor microenvironment greatly affects the delivery efficiency of nanoparticles. METHODS: A careful search of the scientific database was performed to find the tumor microenvironment related papers. Then the papers were concluded and reviewed. RESULTS: In tumor, elevated interstitial fluid pressure, abnormal tumor vasculature, dense tumor extracellular matrix and elevated solid stress considerably hinder the extravasation and intratumor penetration of nanoparticles. Therefore, shaping the tumor microenvironment could improve nanoparticle delivery, including vascular normalization, vasculature promotion therapy, lymph normalization, reducing tumor stroma components, elevating blood pressure, elevating receptor expression, cell cycle arrest and priming by cytotoxic therapy. CONCLUSION: Shaping the tumor microenvironment could considerably enhance the nanoparticles delivery. PMID- 27396755 TI - A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions. AB - Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 +/- 0.08 MUM and a Vmax of 233.1 +/- 17.2 pmol. cm(-2). min(-1). Racemic [(3)H]-ibuprofen uptake could be inhibited by (R)-(-)- and (S)-(+) ibuprofen with IC50 values of 19 MUM (Log IC50 1.39 +/- 0.34) and 0.47 MUM (Log IC50 -0.36 +/- 0.41), respectively. Furthermore, the [(3)H]-ibuprofen uptake rate was increased by decreased extracellular pH but not dependent on Na(+) or Cl(-) ions. The mRNA of Mct1, -2, -4, and -6 as well as Oat1 and -3 were not upregulated by hyperosmolarity. Our findings present strong evidence for the presence of a yet unknown ibuprofen transporter in MDCK I cells. The transporter was upregulated under hyperosmotic culture conditions, and the present study is therefore a starting point for identification of the molecular correlate and potential impact on ibuprofen disposition. PMID- 27396757 TI - alpha-MSH modulates cell adhesion and inflammatory responses of synovial fibroblasts from osteoarthritis patients. AB - INTRODUCTION: The synovium is a target for neuropeptides. Melanocortins have attained particular attention as they elicit antiinflammatory effects. Although synovial fluid from patients with rheumatic diseases contains alpha-melanocyte stimulating hormone (alpha-MSH) it is unknown whether synovial fibroblasts generate alpha-MSH and respond to melanocortins. METHODS: Synovial tissue was obtained from osteoarthritis (OA) patients. Cells were isolated and prepared either as primary mixed synoviocytes or propagated as synovial fibroblasts (OASFs). Melanocortin receptor (MC) and proopiomelanocortin (POMC) expression were investigated by endpoint RT-PCR, immunofluorescence and Western immunoblotting. Functional coupling of MC1 was assessed by cAMP and Ca(2+) assays. Cell adhesion was monitored by the xCELLigence system. Secretion of alpha MSH, tumour necrosis factor (TNF), interleukin (IL)-6 and IL-8 was determined by ELISA. RESULTS: OASFs in vitro expressed MC1. MC1 transcripts were present in synovial tissue and appropriate immunoreactivity was detected in synovial fibroblasts in situ. OASFs contained truncated POMC transcripts but neither full length POMC mRNA, POMC protein nor alpha-MSH were detectable. In accordance with this only truncated POMC transcripts were present in synovial tissue. alpha-MSH increased cAMP dose-dependently but did not alter calcium in OASFs. alpha-MSH also enhanced adhesion of OASFs to fibronectin and reduced TNF, IL-6 and IL-8 secretion in primary mixed synoviocyte cultures. In OASFs, alpha-MSH modulated basal and TNF/IL-1beta-mediated secretion of IL-6 and IL-8. CONCLUSION: Synovial fibroblasts express MC1in vitro and in situ. alpha-MSH elicits biological effects in these cells suggesting an endogenous immunomodulatory role of melanocortins within the synovium. Our results encourage in vivo studies with melanocortins in OA models. PMID- 27396756 TI - Ciclopirox olamine inhibits mTORC1 signaling by activation of AMPK. AB - Ciclopirox olamine (CPX), an off-patent antifungal agent, has recently been identified as a potential anticancer agent. The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation and survival. Little is known about whether and how CPX executes its anticancer action by inhibiting mTOR. Here we show that CPX inhibited the phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), two downstream effector molecules of mTOR complex 1 (mTORC1), in a spectrum of human tumor cells, indicating that CPX inhibits mTORC1 signaling. Using rhabdomyosarcoma cells as an experimental model, we found that expression of constitutively active mTOR (E2419K) conferred resistance to CPX inhibition of cell proliferation, suggesting that CPX inhibition of mTORC1 contributed to its anticancer effect. In line with this, treatment with CPX inhibited tumor growth and concurrently suppressed mTORC1 signaling in RD xenografts. Mechanistically, CPX inhibition of mTORC1 was neither via inhibition of IGF-I receptor or phosphoinositide 3-kinase (PI3K), nor by activation of phosphatase and tensin homolog (PTEN). Instead, CPX inhibition of mTORC1 was attributed to activation of AMP-activated protein kinase (AMPK)-tuberous sclerosis complexes (TSC)/raptor pathways. This is supported by the findings that CPX activated AMPK; inhibition of AMPK with Compound C or ectopic expression of dominant negative AMPKalpha partially prevented CPX from inhibiting mTORC1; silencing TSC2 attenuated CPX inhibition of mTORC1; and CPX also increased AMPK-mediated phosphorylation of raptor (S792). Therefore, the results indicate that CPX exerts the anticancer effect by activating AMPK, resulting in inhibition of mTORC1 signaling. PMID- 27396758 TI - Accessibility and characteristics of memories of the future. AB - Recent research suggests that some imagined future events are encoded in memory, leading to the formation of "memories of the future". However, questions remain regarding the exact components of future event simulations that are encoded and the factors that determine their accessibility. To address these questions, the present study investigated memory for previously imagined future events using both free and cued recall tasks. The results showed that most future event simulations were successfully encoded and remained available in memory after a one week delay, but only some of them were readily accessible, whereas others could only be accessed when relevant cues were provided. Persons and locations were particularly well remembered, suggesting that these components are central to the simulation and memorisation of future events. We also found that memory for future event simulations was related to the clarity and familiarity of represented persons, the subjective feelings of pre-experience and mental time travel, the importance of imagined events to personal goals, and their emotional intensity during the initial simulation phase. Taken together, these findings expand our understanding of the formation, accessibility, and characteristics of memories of the future. PMID- 27396760 TI - A WEB-BASED SURVEY OF MOTHER-INFANT BOND, ATTACHMENT EXPERIENCES, AND METACOGNITION IN POSTTRAUMATIC STRESS FOLLOWING CHILDBIRTH. PMID- 27396759 TI - RUBIC identifies driver genes by detecting recurrent DNA copy number breaks. AB - The frequent recurrence of copy number aberrations across tumour samples is a reliable hallmark of certain cancer driver genes. However, state-of-the-art algorithms for detecting recurrent aberrations fail to detect several known drivers. In this study, we propose RUBIC, an approach that detects recurrent copy number breaks, rather than recurrently amplified or deleted regions. This change of perspective allows for a simplified approach as recursive peak splitting procedures and repeated re-estimation of the background model are avoided. Furthermore, we control the false discovery rate on the level of called regions, rather than at the probe level, as in competing algorithms. We benchmark RUBIC against GISTIC2 (a state-of-the-art approach) and RAIG (a recently proposed approach) on simulated copy number data and on three SNP6 and NGS copy number data sets from TCGA. We show that RUBIC calls more focal recurrent regions and identifies a much larger fraction of known cancer genes. PMID- 27396761 TI - Lung disease left out in the cold. PMID- 27396762 TI - Ukraine struggles to implement flu vaccination. PMID- 27396763 TI - Emotional support animals on commercial flights: a risk to allergic patients. PMID- 27396764 TI - Hope persists for mesothelioma advances despite setbacks. PMID- 27396765 TI - Substantial benefits from finding the most effective BCG strain. PMID- 27396766 TI - Social and household factors affecting child health checkup attendance based on a household survey in Japan. AB - Child health checkups are an important public service to support children's development; however, many children do not attend all the child health checkups that are required by maternal and child health law (i.e., at 1 month, 4 months, 1 and a half years, and 3 years of age). This study aimed to identify social and household factors influencing child health checkup attendance. We used data from a longitudinal household panel study in Japan. The total number of subjects was 2,612 children. We extracted numerous social variables reflecting childcare and conducted logistic regression analyses. In every health checkup, the attendance rate was significantly lower for children whose birth order was 3rd or later. Children whose father graduated from a 4-year college or whose mother had 5 or more communicating neighbors were significantly more likely to attend the 1-and-a half-year checkup. Children whose maternal annual income was in the middle range (1.5 to 5.0 million yen) tended not to attend checkups after 1 and a half years of age. We concluded that the later birth order was the factor of non-attendance. On the other hand, high paternal educational attainment and many communicating neighbors were identified as the factors of attendance. PMID- 27396767 TI - Congenital Malalignment of the Great Toenails With Acute Paronychia. AB - Congenital malalignment of the great toenails (CMGT) has been well documented. In the present case, it was complicated by acute paronychia. It is important for physicians to recognize and treat CMGT to prevent sequelae such as onychocryptosis, onychogryphosis, and recurrent paronychia. PMID- 27396768 TI - Burnout Syndrome in ICU Caregivers: Time to Extinguish! PMID- 27396769 TI - Expanded Drug Delivery Modalities in the Treatment of Pulmonary Arterial Hypertension. PMID- 27396770 TI - Reduced Cardiovascular Morbidity in Obesity-Hypoventilation Syndrome: An Ischemic Preconditioning Protective Effect? PMID- 27396771 TI - Giants in Chest Medicine: Neil R. MacIntyre, MD, FCCP. PMID- 27396772 TI - POINT: Should Pulmonary/ICU Physicians Support Single-payer Health-care Reform? Yes. PMID- 27396773 TI - COUNTERPOINT: Should Pulmonary/ICU Physicians Support Single-payer Health-care Reform? No. PMID- 27396774 TI - Rebuttal From Drs Gaffney, Verhoef, and Hall. PMID- 27396775 TI - Rebuttal From Dr Berdine. PMID- 27396776 TI - An Official Critical Care Societies Collaborative Statement-Burnout Syndrome in Critical Care Health-care Professionals: A Call for Action. AB - Burnout syndrome (BOS) occurs in all types of health-care professionals and is especially common in individuals who care for critically ill patients. The development of BOS is related to an imbalance of personal characteristics of the employee and work-related issues or other organizational factors. BOS is associated with many deleterious consequences, including increased rates of job turnover, reduced patient satisfaction, and decreased quality of care. BOS also directly affects the mental health and physical well-being of the many critical care physicians, nurses, and other health-care professionals who practice worldwide. Until recently, BOS and other psychological disorders in critical care health-care professionals remained relatively unrecognized. To raise awareness of BOS, the Critical Care Societies Collaborative (CCSC) developed this call to action. The present article reviews the diagnostic criteria, prevalence, causative factors, and consequences of BOS. It also discusses potential interventions that may be used to prevent and treat BOS. Finally, we urge multiple stakeholders to help mitigate the development of BOS in critical care health-care professionals and diminish the harmful consequences of BOS, both for critical care health-care professionals and for patients. PMID- 27396781 TI - Analysis of National Trends in Admissions for Pulmonary Embolism. PMID- 27396777 TI - Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial. AB - BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature. RESULTS: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 +/- 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 +/- 1.7 hours per week preimplantation, and this time decreased to 0.6 +/- 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions. CONCLUSIONS: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov. PMID- 27396782 TI - Response. PMID- 27396784 TI - Prediction of Mortality in Pulmonary Embolism Based on Left Atrial Volume Measurements: Do Indexed Values Matter? PMID- 27396785 TI - Response. PMID- 27396783 TI - A Global Survey on Whole Lung Lavage in Pulmonary Alveolar Proteinosis. PMID- 27396786 TI - Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. PMID- 27396787 TI - Response. PMID- 27396788 TI - Direct-Acting Antiviral Medications for Hepatitis C Virus Infection and Pulmonary Arterial Hypertension. PMID- 27396789 TI - Response. PMID- 27396791 TI - Correction to Title, Results, and Conclusion in: Down-Regulated IncRNA F630028O10Rik Contributes to Suppress Lung Cancer in Mice Through Inhibiting miR 223-3p and VEGF Signaling Pathway. PMID- 27396790 TI - Diagnosis of Pneumonia by Lung Ultrasound in Children and Limited Resources Subsets: A Valuable Medical Breakthrough. PMID- 27396792 TI - Correction to Author's Name in: Antisense Long Noncoding RNA LOC285194 is Downregulated in NSCLC and Associated With Poor Prognosis. PMID- 27396793 TI - Withdrawn: Impact of Initial Antibiotic Selection on Adverse Outcomes Among Patients With Severe Sepsis and Septic Shock. PMID- 27396794 TI - The Direct Factor Xa Inhibitor Rivaroxaban Passes Into Human Breast Milk. AB - Thromboembolic disorders frequently require antithrombotic treatment during pregnancy and lactation. Vitamin K antagonists and heparins are the treatment options of choice in breastfeeding women. Factors including the route of administration, discomfort during treatment, and fetal and neonatal safety affect women's choices about anticoagulant therapy. Direct-acting oral anticoagulants (DOACs) have emerged as alternatives to these agents and may offer advantages compared with vitamin K antagonists. As breastfeeding women were excluded from clinical trials evaluating DOACs, no safety and efficacy data are available for these special patients and, crucially, estimates for infant exposure are lacking. Therefore, the manufacturer recommends against using DOACs during the lactation period. We present the case of a patient who stopped breastfeeding owing to a diagnosis of postpartum cardiomyopathy. Anticoagulation with enoxaparin that commenced after the diagnosis of postpartum pulmonary embolism was switched to rivaroxaban. At that time, breast milk samples were collected and rivaroxaban concentrations were determined by liquid chromatography tandem-mass spectrometry. Rivaroxaban appears in human breast milk in comparatively small amounts; its safety has not been determined. PMID- 27396795 TI - A Woman in Her 70s With Profound Hypoxemia. PMID- 27396796 TI - An 80-Year-Old Woman With Progressive Shortness of Breath and a Mediastinal Mass. AB - An 80-year-old woman from Iran presented to our institution for evaluation of insidious onset of dyspnea and progressive hypoxemia. She had a history of hypertension, COPD attributed to secondhand smoke, and an unprovoked pulmonary embolus that was treated with lifelong anticoagulation. In addition, she had a history of latent TB status posttreatment with isoniazid 10 years prior. One year ago, home oxygen therapy was started at 4 L/min via nasal cannula, and because of her decline, her son had brought her to the United States 3 months earlier for medical help. After a contrast-enhanced thoracic CT scan followed by a nondiagnostic thoracentesis, another hospital informed her that she likely had inoperable lung cancer. She presented to our institution for a second opinion. PMID- 27396797 TI - A 56-Year-Old, Otherwise Healthy Woman Presenting With Light-headedness and Progressive Shortness of Breath. AB - A 56-year-old white woman was referred to the pulmonary clinic for evaluation of unexplained shortness of breath. She enjoyed good health until 3 months prior to this visit when she reported experiencing recurrent episodes of shortness of breath and oppressive retrosternal chest discomfort with radiation to the neck. Episodes lasting 5 to 10 min often occurred at rest and were inconsistently related to physical activity. These symptoms became progressively worse and were often associated with light-headedness and presyncope. Her past medical history was uneventful apart from a prior diagnosis of breast cysts and suspected prolactinoma. Her symptoms escalated to such a level that she was forced to seek urgent medical attention at our institutional ED on two separate occasions in the preceding weeks. These visits precipitated a number of investigations and, eventually, a referral to the pulmonary clinic. PMID- 27396799 TI - An 82-Year-Old Woman With Ongoing Dyspnea. PMID- 27396798 TI - Incidence of Pneumothorax in Patients With Lymphangioleiomyomatosis Undergoing Pulmonary Function and Exercise Testing. AB - Because pneumothorax is frequent in lymphangioleiomyomatosis, patients have expressed concerns regarding the risk of pneumothorax associated with pulmonary function or exercise testing. Indeed, pneumothorax has been reported in patients with lung disease after both of these tests. The aim of this study was to determine the incidence of pneumothorax in patients with lymphangioleiomyomatosis during admissions to the National Institutes of Health Clinical Research Center between 1995 and 2015. Medical records were reviewed to identify patients who had a pneumothorax during their stay at the National Institutes of Health. A total of 691 patients underwent 4,523 pulmonary function tests and 1,900 exercise tests. Three patients developed pneumothorax after pulmonary function tests and/or exercise tests. The incidence of pneumothorax associated with lung function testing was 0.14 to 0.29 of 100 patients or 0.02 to 0.04 of 100 tests. The incidence of pneumothorax in patients undergoing exercise testing was 0.14 to 0.28 of 100 patients or 0.05 to 0.10 of 100 tests. The risk of pneumothorax associated with pulmonary function or exercise testing in patients with lymphangioleiomyomatosis is low. PMID- 27396800 TI - Diagnostic Accuracy of Ultrasound, Contrast-enhanced CT, and Conventional MRI for Differentiating Leiomyoma From Leiomyosarcoma. AB - RATIONALE AND OBJECTIVES: This study aimed to determine whether uterine leiomyoma can be distinguished from uterine leiomyosarcoma on ultrasound (US), computed tomography (CT), and/or magnetic resonance imaging (MRI) without diffusion weighted imaging. MATERIALS AND METHODS: Institutional review board approval was obtained and informed consent was waived for this Health Insurance Portability and Accountability Act-compliant retrospective case-control diagnostic accuracy study. All subjects with resected uterine leiomyosarcoma diagnosed over a 17-year period (1998-2014) at a single institution for whom pre-resection US (n = 10), CT (n = 11), or MRI (n = 7) was available were matched by tumor size and imaging modality with 28 subjects with resected uterine leiomyoma. Six blinded radiologists (three attendings, three residents) assigned 5-point Likert scores for the following features: (1) margins, (2) necrosis, (3) hemorrhage, (4) vascularity, (5) calcifications, (6) heterogeneity, and (7) likelihood of malignancy (primary end point). Mean suspicion scores were calculated and receiver operating characteristic curves were generated. The ability of individual morphologic features to predict malignancy was assessed with logistic regression. RESULTS: Mean suspicion scores were 2.5 +/- 1.2 (attendings) and 2.4 +/- 1.3 (residents) for leiomyoma, and 2.7 +/- 1.3 (attendings) and 2.7 +/- 1.4 (residents) for leiomyosarcoma. The areas under the receiver operating characteristic curves (range: 0.330-0.685) were not significantly different from chance, either overall (P = .36-.88) or by any modality (P = .28-.96), for any reader. Reader experience had no effect on diagnostic accuracy. No morphologic parameter was significantly predictive of malignancy (P = .10-.97). CONCLUSIONS: Uterine leiomyoma cannot be differentiated accurately from leiomyosarcoma on US, CT, or MRI without diffusion-weighted imaging. PMID- 27396801 TI - Advances in perioperative management of high-risk patients: The A-team in charge. PMID- 27396802 TI - Preoperative patient assessment: Identifying patients at high risk. AB - Postoperative mortality remains alarmingly high with a mortality rate ranging between 0.4% and 4%. A small subgroup of multimorbid and/or elderly patients undergoing different surgical procedures naturally confers the highest risk of complications and perioperative death. Therefore, preoperative assessment should identify these high-risk patients and stratify them to individualized monitoring and treatment throughout all phases of perioperative care. A "tailored" perioperative approach might help further reduce perioperative morbidity and mortality. This article aims to elucidate individual morbidity-specific risks. It further suggests approaches to detect patients at the risk of perioperative complications. PMID- 27396803 TI - Preparing the patient for surgery to improve outcomes. AB - The time between contemplation of surgery and the procedure offers a window of opportunity to optimize patients' nutritional, functional and psychological state prior to surgery. Traditionally, preoperative pathways have focused on the underlying disease process and 'fitness for surgery' with physical pre-assessment and risk counselling late in the pathway when little time is available to intervene. With an increasingly elderly and co-morbid surgical population, early physiological assessment and multidisciplinary collaborative decision-making is increasingly important. Multimodal prehabilitation programmes may improve surgical outcome, facilitating rapid recovery from surgery and limiting post operative functional dependence. Patient education and engagement is important if compliance with behavioural change is to be achieved and maintained. To date, there has been evidence supporting preoperative exercise training, smoking cessation, reduction in alcohol intake, anaemia management and psychosocial support. Further research is needed to identify the most effective elements of these complex preoperative interventions, as well as their optimum timing and duration. PMID- 27396804 TI - Patient blood management equals patient safety. AB - Patient blood management (PBM) can be defined in many ways and may consist of hundreds of single measures to improve patient safety. Traditionally, PBM is based on three pillars and defined as (i) optimization of the endogenous red blood cell (RBC) mass through the targeted stimulation of erythropoiesis and the treatment of modifiable underlying disorders; (ii) minimization of diagnostic, interventional, and surgical blood loss to preserve the patient's RBC mass; and (iii) optimization of the patient-specific tolerance to anemia through strict adherence to physiological transfusion thresholds [1-4]. However, for this review, we have chosen the following three peri-interventional parts: (1) diagnosis and therapy of anemia, (2) optimal hemotherapy, and (3) minimization of hospital-acquired anemia. PBM is an evidence-based, multidisciplinary preventive, and therapeutic approach focusing each patient. The PBM concept involves the use of safe and effective medical and surgical methods and techniques designed to prevent peri-interventional anemia, rationalize use of blood products, and set good blood management measures in an effort to improve patient safety and outcome. PMID- 27396805 TI - Pharmacological modification of the perioperative stress response in noncardiac surgery. AB - The perioperative period is associated with alterations in the neuroendocrine, metabolic, and immune systems, referred to as "stress response." The resultant increased sympathetic activity and elevated serum concentrations of catecholamines may adversely affect the cardiovascular system, resulting in cardiovascular instability (hypertension, tachycardia, and arrhythmia), morbidity (myocardial ischemia, myocardial infarction, and stroke), and mortality (cardiac death and fatal stroke), particularly in patients at an elevated cardiovascular risk and with reduced cardiovascular reserve. Various strategies have been used to ameliorate the adverse perioperative cardiovascular sequelae of the perioperative stress response. Effective pharmacologic blunting of the stress response plays a crucial role in perioperative cardiac risk reduction strategies. In this context, the role of beta-adrenoceptor blockers, alpha2-adrenoceptor agonists, and statins has been extensively examined. This chapter evaluates the available evidence with respect to treatment efficacy of these commonly prescribed drugs in patients undergoing noncardiac surgery. PMID- 27396806 TI - Do ultrasound-guided regional blocks signify a new paradigm in high-risk patients? AB - It has been suggested for many years that regional anaesthesia is advantageous in high-risk patients, either as the sole anaesthetic or in combination with general anaesthesia. Regional techniques are safe and even more so when guided by ultrasound. In the high-risk patient population, ultrasound-guided regional anaesthesia (UGRA) can help decrease risk of perioperative morbidity and improve short-term as well as long-term outcomes, particularly in the orthopaedic, vascular, oncologic and chronic pain patient populations. Nevertheless, complications do still occur and benefits of a specific regional nerve blockade need to be weighed against potential risks on an individual basis. The emergence of reasonably priced, easy-to-use ultrasound machines facilitates regional anaesthesia, and this kind of anaesthesia may become the standard of care in high risk patients. PMID- 27396807 TI - Monitoring high-risk patients: minimally invasive and non-invasive possibilities. AB - Over the past decades, there has been considerable progress in the field of less invasive haemodynamic monitoring technologies. Substantial evidence has accumulated, which supports the continuous measurement and optimization of flow based variables such as stroke volume, that is, cardiac output, in order to prevent occult hypoperfusion and consequently to improve patients' outcome in the perioperative setting. However, there is a striking gap between the developments in haemodynamic monitoring and the increasing evidence to implement defined treatment protocols based on the measured variables, and daily clinical routine. Recent trials have shown that perioperative morbidity and mortality is higher than anticipated. This emphasizes the need for the anaesthesia community to address this issue and promotes the implementation of proven concepts into clinical practice in order to improve patients' outcome, especially in high-risk patients. The advances in minimally invasive and non-invasive monitoring techniques can be seen as a driving force in this respect, as the degree of invasiveness of any monitoring tool determines the frequency of its application, especially in the operating room (OR). From this point of view, we are very confident that some of these minimally invasive and non-invasive haemodynamic monitoring technologies will become an inherent part of our monitoring armamentarium in the OR and in the intensive care unit (ICU). PMID- 27396808 TI - Goal-directed therapy to maintain haemostasis. AB - Perioperative goal-directed therapy typically involves the use of haemodynamic targets to optimise oxygen delivery. Common goals include stroke volume, cardiac output and arterial blood pressure, although future protocols may also incorporate an assessment of vascular tone and the microcirculation. This article reviews the current evidence for goal-directed therapy and discusses future directions. PMID- 27396809 TI - How to treat post-operative complications: An evidence-based approach. AB - Post-operative complication can be defined as any deviation from the normal post operative course. The majority of post-operative complications affects the subgroup of high-risk patients, and they are clearly associated with increased hospital length of stay and mortality. This review deals with the principal complications occurring during the post-operative period. In particular, we describe the preventive and management strategies to face pulmonary, cardiac, renal and neurological complications. PMID- 27396810 TI - How to avoid catastrophic events on the ward. AB - The number and disease severity of hospitalized patients have risen steadily. At the same time, the length of stay in the hospital has decreased and there is an increasing shortage of nursing staff and physicians. In order to enable a timely treatment of serious in-house emergencies (i.e., cardiac arrest and cardiopulmonary resuscitation) and to decrease the risk of unexpected deaths, early detection and treatment of critically ill patients are of paramount importance. Therefore, patients should be monitored according to their disease severity in order to detect a critical change in vital signs. Early critical incident warning systems may play a role in this context. Currently, different rapid warning systems have been established, but data that allow a choice for a certain system are still lacking. Alarm criteria based on a single variable (single-parameter system) are a simple, but less sensitive alternative to indicate a serious adverse event. Scoring systems enable early detection of critically ill patients and may trigger early treatment by staff specially trained to handle emergency situations. PMID- 27396811 TI - Dose-volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: Results from the prospective multicenter EMBRACE study. AB - PURPOSE: To establish dose volume-effect relationships predicting late rectal morbidity in cervix cancer patients treated with concomitant chemoradiation and MRI-guided adaptive brachytherapy (IBABT) within the prospective EMBRACE study. MATERIAL AND METHOD: All patients were treated with curative intent according to institutional protocols with chemoradiation and IGABT. Reporting followed the GEC ESTRO recommendations ( [Formula: see text] , [Formula: see text] ), applying bioeffect modeling (linear quadratic model) with equieffective doses (EQD23). Morbidity was scored according to the CTC-AE 3.0. Dose-effect relationships were assessed using comparisons of mean doses, the probit model and log rank tests on event-free periods. RESULTS: 960 patients were included. The median follow-up was 25.4months. Twenty point one percent of the patients had grade 1 events, 6.0% grade 2, 1.6% grade 3 and 0.1%, grade 4. The mean DICRU, [Formula: see text] , and [Formula: see text] were respectively: 66.2+/-9.1Gy, 72.9+/-11.9Gy, and 62.8+/-7.6Gy. Increase of dose was associated with increase in severity of single endpoints and overall rectal morbidity (grade 1-4) (p<0.001-0.026), except for stenosis (p=0.24-0.31). The probit model showed significant relationships between the [Formula: see text] , [Formula: see text] , and DICRU and the probability of grade 1-4, 2-4, and 3-4 rectal events. The equieffective [Formula: see text] for a 10% probability for overall rectal grade?2 morbidity was 69.5Gy (p<0.0001). After sorting patients according to 6 [Formula: see text] levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A [Formula: see text] ?75Gy was associated with a 12.5% risk of fistula at 3years versus 0-2.7% for lower doses (p>0.001). A [Formula: see text] <65Gy was associated with a two times lower risk of proctitis than [Formula: see text] ?65Gy. CONCLUSIONS: Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose volume ( [Formula: see text] , [Formula: see text] ) and dose-point (DICRU) parameters. A [Formula: see text] ?65Gy is associated with more minor and less frequent rectal morbidity, whereas a [Formula: see text] ?75Gy is associated with more major and more frequent rectal morbidity. PMID- 27396812 TI - Anatomical MCL reconstruction following TKA. AB - Adequate ligament balancing has a tremendous impact on successful total knee arthroplasty. In case of instability, severely disabling symptoms require revision surgery. Here we present a case of early total knee arthroplasty failure due to secondary valgus laxity, which was successfully treated with medial collateral ligament (MCL) reconstruction. For anatomical MCL reconstruction, a flattened semitendinosus autograft was used to reconstruct the superficial medial collateral and the posterior oblique ligament. PMID- 27396813 TI - Role of histone deacetylases(HDACs) in progression and reversal of liver fibrosis. AB - Liver fibrosis refers to a reversible wound healing process response to chronic liver injuries. Activation of hepatic stellate cells (HSCs) is closely correlated with the development of liver fibrosis. Histone deacetylases(HDACs) determine the acetylation levels of core histones to modulate expression of genes. To demonstrate the link between HDACs and liver fibrosis, CCl4-induced mouse liver fibrosis model and its spontaneous reversal model were established. Results of the current study demonstrated that deregulation of liver HDACs may involved in the development of liver fibrosis. Among 11 HDACs tested in our study (Class I, II, and IV HDACs), expression of HDAC2 was maximally increased in CCl4-induced fibrotic livers but decreased after spontaneous recovery. Moreover, expression of HDAC2 was elevated in human liver fibrotic tissues. In this regard, the potential role of HDAC2 in liver fibrosis was further evaluated. Our results showed that administration of HSC-T6 cells with transforming growth factor-beta1 (TGF-beta1) resulted in an increase of HDAC2 protein expression in dose- and time-dependent manners. Moreover, HDAC2 deficiency inhibited HSC-T6 cell proliferation and activation induced by TGF-beta1. More importantly, the present study showed HDAC2 may regulate HSCs activation by suppressing expression of Smad7, which is a negative modulator in HSCs activation and liver fibrosis. Collectively, these observations revealed that HDAC2 may play a pivotal role in HSCs activation and liver fibrosis while deregulation of HDACs may serve as a novel mechanism underlying liver fibrosis. PMID- 27396814 TI - Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling. AB - To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (<0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. PMID- 27396815 TI - RCT of a 6-month programmed sports therapy (PST) in patients with haemophilia - Improvement of physical fitness. AB - Physical fitness is of major importance for patients with haemophilia (PwH) but is highly influenced by bleeding episodes. Although some cohort studies describe an improvement of physical fitness after training intervention, randomized controlled studies (RCT) in PwH are still rare. AIM: The aim of this study was to prove the enhancement of physical work capacity in PwH by programmed sports therapy (PST). METHODS: This RCT includes a training period over six months. Sixty-four PwH with moderate (n = 5) to severe (n = 59) haemophilia A (n = 57) and B (n = 7) were randomized into two groups - training intervention group (IG) and control group (CG) by block randomization. Complex strength measurements, joint score, coordination check and a 12-min walking test were carried out before and after training intervention. RESULTS: Significant differences were tested in M. triceps brachii (Delta+0.62 N kg(-1) ), biceps brachii (Delta+1.25 N kg(-1) ), latissimus dorsi (Delta+0.59 N kg(-1) ), rectus abdominis (Delta+0.51 N kg(-1) ), biceps femoris (right: Delta+0.68 N kg(-1) ; left: Delta+0.59 N kg(-1) ) and the quadriceps femoris (right: Delta+0.71 N kg(-1) ; left: Delta+0.55 N kg(-1) ) after intervention between the two groups (all p <= 0.003). Furthermore, an increase in distance (Delta+171.5 m) covered in the 12-min walking test (P = 0.011) was observed. Regarding one-leg stand, a significant improvement (P = 0.037) in the IG (Delta+2.2 s right leg) after intervention could be determined. CONCLUSION: For the first time, a study with a corresponding number of adult PwH in a RCT-design showed that programmed sport therapy with specific instructions over 6 months has a positive effect on physical performance of PwH, independent of constitution and disease process. PMID- 27396817 TI - B cells and antibodies in progressive multiple sclerosis: Contribution to neurodegeneration and progression. AB - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination, axonal degeneration and gliosis. The progressive form of MS is an important research topic as not much is known about its underlying mechanisms and no therapy is available. Although progressive MS is traditionally considered to be driven by neurodegeneration, compartmentalized CNS inflammation is currently accepted as one of the driving processes behind neurodegeneration and progression. In this review, the involvement of B cells and antibodies in progressive MS is discussed. The identification of meningeal ectopic B cell follicles in secondary progressive MS (SPMS) patients and the successful use of B cell-depleting therapy in primary progressive MS (PPMS) patients have underlined the importance of B cells in progressive MS. Proof is also available for the role of antibodies in neurodegeneration and progression in MS. Here, oligoclonal immunoglobulin M (IgM) production and autoreactive antibodies are described, with a focus on antibodies directed against sperm associated antigen 16 (SPAG16). Further research into the role of B cells and autoantibodies in MS progression can lead to novel prognostic and theranostic opportunities. PMID- 27396818 TI - Gene- gene interaction between CYP2J2 and PPAR -gamma gene on late-onset Alzheimer's disease in the eastern Chinese Han population. AB - AIMS: To investigate the impact of PPAR -gamma and CYP2J2 gene single nucleotide polymorphisms (SNPs) and gene- gene interactions on late-onset Alzheimer's disease (LOAD) risk in Chinese Han population. METHODS: A total of 880 participants (514 males, 366 females), with a mean age of 81.7+/-15.9years old are selected, including 430 LOAD patients and 450 normal participants. Generalized multifactor dimensionality reduction (GMDR) is used to examine interaction among six SNPs, odds ratio (OR) and 95% confident interval (95%CI) are calculated by Logistic regression model. RESULTS: Logistic regression analysis showed that increased LOAD risks are associated with T allele of the rs1155002 polymorphism, adjusted OR (95%CI)=1.46 (1.12-1.90), and T allele of the rs890293 polymorphism, adjusted OR (95%CI)=1.65 (1.30-2.06), and G allele of the rs1805192 polymorphism, adjusted OR (95%CI)=1.70 (1.25-2.27). We also found a potential gene-gene interaction between rs890293 and rs1805192. Participants with GT or TT of rs890293 and CG or GG of rs1805192 genotype have the highest LOAD risk, compared to participants with GG of rs890293 and CC of rs1805192 genotype, OR (95%CI)=2.22 (1.63 -2.85), after covariates adjustment. CONCLUSIONS: rs1155002, rs890293 and rs1805192 polymorphism are associated with increased LOAD risk. Participants with GT or TT of rs890293 and CG or GG of rs1805192 genotype have the highest LOAD risk. PMID- 27396819 TI - Olympics shine a light on slums and pollution in Rio. PMID- 27396816 TI - Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease. AB - Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naive B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease. PMID- 27396820 TI - Synthesis of graphene and related two-dimensional materials for bioelectronics devices. AB - In recent years, graphene and related two-dimensional (2D) materials have emerged as exotic materials in nearly every fields of fundamental science and applied engineering. The latest progress has shown that these 2D materials could have a profound impact on bioelectronics devices. For the construction of these bioelectronics devices, these 2D materials were generally synthesized by the processes of exfoliation and chemical vapor deposition. In particular, the macrostructures of these 2D materials have also been realized by these two processes, which have shown great potentials in the self-supported and special purpose biosensors. Due to the high specific surface area, subtle electron properties, abundant surface atoms of these 2D materials, the as-constructed bioelectronics devices have exhibited enhanced performance in the sensing of small biomolecules, heavy metals, pH, protein and DNA. The aim of this review article is to provide a comprehensive scientific progress in the synthesis of 2D materials for the construction of five typical bioelectronics devices (electrochemical biosensors, FET-based biosensors, piezoelectric devices, electrochemiluminescence devices and supercapacitors) and to overview the present status and future perspective of the applications of these bioelectronics devices based on 2D materials. PMID- 27396821 TI - Pin-based electrochemical glucose sensor with multiplexing possibilities. AB - This work describes the use of mass-produced stainless-steel pins as low-cost electrodes to develop simple and portable amperometric glucose biosensors. A potentiostatic three-electrode configuration device is designed using two bare pins as reference and counter electrodes, and a carbon-ink coated pin as working electrode. Conventional transparency film without any pretreatment is used to punch the pins and contain the measurement solution. The interface to the potentiostat is very simple since it is based on a commercial female connection. This electrochemical system is applied to glucose determination using a bienzymatic sensor phase (glucose oxidase/horseradish peroxidase) with ferrocyanide as electron-transfer mediator, achieving a linear range from 0.05 to 1mM. It shows analytical characteristics comparable to glucose sensors previously reported using conventional electrodes, and its application for real food samples provides good results. The easy modification of the position of the pins allows designing different configurations with possibility of performing simultaneous measurements. This is demonstrated through a specific design that includes four pin working-electrodes. Different concentrations of antibody labeled with alkaline phosphatase are immobilized on the pin-heads and after enzymatic conversion of 3-indoxylphosphate and silver nitrate, metallic silver is determined by anodic stripping voltammetry. PMID- 27396822 TI - Carboxyl-functionalized graphene oxide composites as SPR biosensors with enhanced sensitivity for immunoaffinity detection. AB - This work demonstrates the excellent potential of carboxyl-functionalized graphene oxide (GO-COOH) composites to form biocompatible surfaces on sensing films for use in surface plasmon resonance (SPR)-based immunoaffinity biosensors. Carboxyl-functionalization of graphene carbon can modulate its visible spectrum, and can therefore be used to improve and control the plasmonic coupling mechanism. The binding properties of the molecules between a sensing film and a protein were elucidated at various flow rates of those molecules. The bio specific binding interaction among the molecules was investigated by performing an antigen and antibody affinity immunoassay. The results thus obtained revealed that the overall affinity binding value, KA, of the Au/GO-COOH chip can be significantly enhanced by up to ~5.15 times that of the Au/GO chip. With respect to the shifts of the SPR angles of the chips, the affinity immunoassay interaction at a BSA concentration of 1MUg/ml for an Au/GO-COOH chip, an Au/GO chip and a traditional SPR chip are 35.5m degrees , 9.128m degrees and 8.816m degrees , respectively. The enhancement of the antigen-antibody interaction of the Au/GO-COOH chip cause this chip to become four times as sensitive to the SPR angle shift and to have the lowest antibody detection limit of 0.01pg/ml. These results indicate the potential of the chip in detecting specific proteins, and the development of real-time in vivo blood analysis and diagnosis based on cancer tumor markers. PMID- 27396823 TI - Framingham score, renal dysfunction, and cardiovascular risk in liver transplant patients. AB - Cardiovascular (CV) events represent major impediments to the long-term survival of liver transplantation (LT) patients. The aim of this study was to assess whether the Framingham risk score (FRS) at transplantation can predict the development of post-LT cardiovascular events (CVEs). Patients transplanted between 2006 and 2008 were included. Baseline features, CV risk factors, and CVEs occurring after LT (ischemic heart disease, stroke, heart failure, de novo arrhythmias, and peripheral arterial disease) were recorded. In total, 250 patients (69.6% men) with a median age of 56 years (range, 18-68 years) were included. At transplantation, 34.4%, 34.4%, and 33.2% of patients, respectively, had a low, moderate, and high FRS with a median FRS of 14.9 (range, 0.09-30); 14.4% of LT recipients developed at least 1 CVE at a median of 2.619 years (range, 0.006-6.945 years). In the univariate analysis, factors associated with the development of CVEs were the continuous FRS at LT (P = 0.003), age (P = 0.007), creatinine clearance [estimated glomerular filtration rate (eGFR); P = 0.020], and mycophenolate mofetil use at discharge (P = 0.011). In the multivariate analysis, only the eGFR [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.97-1.00; P = 0.009] and FRS (HR, 1.06; 95% CI, 1.02-1.10; P = 0.002) remained in the model. Moreover, an association was also found between the FRS and overall survival (P = 0.004) with 5-year survival rates of 82.5%, 77.8%, and 61.4% for the low-, moderate-, and high-risk groups, respectively. Continuous FRS, eGFR, and hepatitis C virus infection were independent risk factors for overall mortality. In our series, the FRS and eGFR at LT were able to predict the development of post-LT CVEs and poor outcomes. Liver Transpl 21:812-822, 2015. (c) 2015 AASLD. PMID- 27396825 TI - Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling. AB - The GM-CSF, IL-3, and IL-5 receptors constitute the betac family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:alpha subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures of both binary and ternary receptor complexes for the same cytokine. We have now solved the structure of the binary GM CSF:GMRalpha complex at 2.8-A resolution and compared it with the structure of the ternary complex, revealing distinct conformational changes. Guided by these differences we performed mutational and functional studies that, importantly, show GMRalpha interactions playing a major role in receptor signaling while betac interactions control high-affinity binding. These results support the notion that conformational changes underlie the mechanism of GM-CSF receptor activation and also suggest how related type I cytokine receptors signal. PMID- 27396826 TI - Role of the PFXFATG[G/Y] Motif in the Activation of SdrG, a Response Regulator Involved in the Alphaproteobacterial General Stress Response. AB - Two-component systems are major signal transduction pathways, which consist of histidine kinases and response regulators that communicate through phosphorylation. Here, we highlight a distinct class of single-domain response regulators containing the PFXFATG[G/Y] motif that are activated by a mechanism distinct from the Y-T coupling described for prototypical receiver domains. We first solved the structures of inactive and active SdrG, a representative of the FAT GUY family, and then biochemically and genetically characterized variants in which residues in this motif were mutated. Our results support a model of activation mainly driven by a conserved lysine and reveal that the rotation of the threonine induces the reorganization of several aromatic residues in and around the PFXFATG[G/Y] motif to generate intermediates resembling those occurring during classical Y-T coupling. Overall, this helps define a new subfamily of response regulators that emerge as important players in physiological adaptation. PMID- 27396824 TI - Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 Reveal Distinct Binding Mechanisms between Substrate Receptors and Shuttle Factors of the Proteasome. AB - Three receptors (Rpn1/S2/PSMD2, Rpn10/S5a, Rpn13/Adrm1) in the proteasome bind substrates by interacting with conjugated ubiquitin chains and/or shuttle factors (Rad23/HR23, Dsk2/PLIC/ubiquilin, Ddi1) that carry ubiquitinated substrates to proteasomes. We solved the structure of two such receptors with their preferred shuttle factor, namely hRpn13(Pru):hPLIC2(UBL) and scRpn1 T1:scRad23(UBL). We find that ubiquitin folds in Rad23 and Dsk2 are fine-tuned by residue substitutions to achieve high affinity for Rpn1 and Rpn13, respectively. A single substitution in hPLIC2 yields enhanced interactions with the Rpn13 ubiquitin contact surface and sterically blocks hRpn13 binding to its preferred ubiquitin chain type, K48-linked chains. Rpn1 T1 binds two ubiquitins in tandem and we find that Rad23 binds exclusively to the higher-affinity Helix28/Helix30 site. Rad23 contacts at Helix28/Helix30 are optimized compared to ubiquitin by multiple conservative amino acid substitutions. Thus, shuttle factors deliver substrates to proteasomes through fine-tuned ubiquitin-like surfaces. PMID- 27396827 TI - Hybrid Structure of a Dynamic Single-Chain Carboxylase from Deinococcus radiodurans. AB - Biotin-dependent acyl-coenzyme A (CoA) carboxylases (aCCs) are involved in key steps of anabolic pathways and comprise three distinct functional units: biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyl transferase (CT). YCC multienzymes are a poorly characterized family of prokaryotic aCCs of unidentified substrate specificity, which integrate all functional units into a single polypeptide chain. We employed a hybrid approach to study the dynamic structure of Deinococcus radiodurans (Dra) YCC: crystal structures of isolated domains reveal a hexameric CT core with extended substrate binding pocket and a dimeric BC domain. Negative-stain electron microscopy provides an approximation of the variable positioning of the BC dimers relative to the CT core. Small-angle X-ray scattering yields quantitative information on the ensemble of Dra YCC structures in solution. Comparison with other carrier protein-dependent multienzymes highlights a characteristic range of large-scale interdomain flexibility in this important class of biosynthetic enzymes. PMID- 27396828 TI - Pushing the Envelope: Dengue Viral Membrane Coaxed into Shape by Molecular Simulations. AB - Dengue virus is a flavivirus responsible for millions of infections per year. Its surface contains a phospholipid bilayer, within which are embedded the envelope (E) and membrane (M) proteins, arranged with icosahedral geometry. Exposure to low pH triggers the E proteins to undergo conformational changes, which precede fusion with the host cell membrane and release of the viral genome. The flavivirus membrane exhibits significant local curvature and deformation, as revealed by cryoelectron microscopy (cryo-EM), but its precise structure and interactions with envelope components remain unclear. We now report simulations of the dengue viral particle that refine its envelope structure in unprecedented detail. Our final models are morphologically consistent with cryo-EM data, and reveal the structural basis for membrane curvature. Electrostatic interactions increased envelope complex stability; this coupling has potential functional significance in the context of the viral fusion mechanism and infective states. PMID- 27396831 TI - Editorial Comment. PMID- 27396829 TI - Dynamic Local Polymorphisms in the Gbx1 Homeodomain Induced by DNA Binding. AB - The Gastrulation Brain Homeobox 1 (Gbx1) gene encodes the Gbx1 homeodomain that targets TAATTA motifs in double-stranded DNA (dsDNA). Residues Glu17 and Arg52 in Gbx1 form a salt bridge, which is preserved in crystal structures and molecular dynamics simulations of homologous homeodomain-DNA complexes. In contrast, our nuclear magnetic resonance (NMR) studies show that DNA binding to Gbx1 induces dynamic local polymorphisms, which include breaking of the Glu17-Arg52 salt bridge. To study this interaction, we produced a variant with Glu17Arg and Arg52Glu mutations, which exhibited the same fold as the wild-type protein, but a 2-fold reduction in affinity for dsDNA. Analysis of the NMR structures of the Gbx1 homeodomain in the free form, the Gbx1[E17R,R52E] variant, and a Gbx1 homeodomain-DNA complex showed that stabilizing interactions of the Arg52 side chain with the DNA backbone are facilitated by transient breakage of the Glu17 Arg52 salt bridge in the DNA-bound Gbx1. PMID- 27396830 TI - Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer. AB - Cullin-RING E3 ligases (CRLs) are elongated and bowed protein complexes that transfer ubiquitin over 60 A to proteins targeted for proteasome degradation. One such CRL contains the ankyrin repeat and SOCS box protein 9 (ASB9), which binds to and partially inhibits creatine kinase (CK). While current models for the ASB9 CK complex contain some known interface residues, the overall structure and precise interface of the ASB9-CK complex remains unknown. Through an integrative modeling approach, we report a third-generation model that reveals precisely the interface interactions and also fits the shape of the ASB9-CK complex as determined by small-angle X-ray scattering. We constructed an atomic model for the entire CK-targeting CRL to uncover dominant modes of motion that could permit ubiquitin transfer. Remarkably, only the correctly docked CK-containing E3 ligase and not incorrectly docked structures permitted close approach of ubiquitin to the CK substrate. PMID- 27396832 TI - Author Reply. PMID- 27396833 TI - Neuroanatomical evidence for the involvement of beta-endorphin during reproductive stress response in the fish Oreochromis mossambicus. AB - Although neuroendocrine regulation of stress response involving hypothalamo pituitary-adrenal axis is well established in mammals, the mechanism of functioning of endocrine-stress axis is not completely elucidated in fish. Our previous studies suggested a possible role for the opioidergic mediation of reproductive stress response in fish. In the present investigation, by immunocytochemical approach, we studied the distribution of beta-endorphin (beta EP) secreting neurons in the brain of the tilapia Oreochromis mossambicus exposed to aquacultural stressors. Intensely stained beta-EP immunoreactive neurons were encountered in the nucleus lateralis tuberis (NLT) region during previtellogenic and vitellogenic phases in both controls and in fish exposed to aquacultural stressors. Furthermore, at the end of the prespawning phase in controls, weak staining in beta-EP neurons was accompanied by intensely stained luteinizing hormone (LH) immunoreactive cells in the proximal pars distalis (PPD) of the pituitary gland and a significantly higher gonadosomatic and hepatosomatic indices, suggesting the attenuation of inhibitory effect of beta-EP on reproductive axis prior to spawning. However, in fish exposed to stressors, several darkly stained beta-EP immunoreactive cells with dense fibre projections towards the hypothalamo-hypophysial tract were concomitant with weakly immunoreactive LH content in the PPD of the pituitary gland and a significantly lower gonadosomatic and hepatosomatic indices compared to those of controls. These results suggest that stress-induced activation of beta-EP secreting neurons in the NLT region might lead to the inhibition of LH secreting cells-ovary axis in fish. PMID- 27396834 TI - A hand-portable digital linear ion trap mass spectrometer. AB - A hand-portable digital linear ion trap mass spectrometer (DLIT-MS) has been developed for VOC analysis. It has a weight of 18 kg with dimensions of 49 cm * 39 cm * 16 cm, and consumes an average power of ca. 60 W. As a result of the introduction of a digital waveform, the DLIT-MS can be driven at a lower voltage (+/-100 V) to cover a mass range of 30-300 Th with a unit resolution. Compact electronics has been designed to control the DLIT-MS and record mass spectra. The mass drift was reduced after the improvement in electronics to stabilize the digital waveform voltage during the mass scan. Tandem mass spectrometry (MS) has been achieved by using digital asymmetric waveform isolation (DAWI), forward and reverse scan, and collision induced dissociation (CID). The isolation and CID efficiency for methyl salicylate were 83.9% and 81.3%, respectively. A novel buffer gas inlet system was designed to enhance the sensitivity and allow easy and safe use of the instrument. Limits of detection below 1 ppbv were obtained for several mixed gaseous samples. PMID- 27396835 TI - Application of a computer-assisted structure elucidation program for the structural determination of a new terpenoid aldehyde with an unusual skeleton. AB - The structure of a novel compound from Adansonia digitata has been elucidated, and its 1 H and 13 C NMR spectra have been assigned employing a variety of one dimensional and two-dimensional NMR techniques without degradative chemistry. The Advanced Chemistry Development ACD/Structure Elucidator software was important for determining part of this structure that contained a fused bicyclic system with very few hydrogen atoms, which in turn, exhibited essentially no discriminating HMBC connectivities throughout that portion of the molecule. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27396836 TI - Importance of Hydrogen Bonding in Fine Tuning the [2Fe-2S] Cluster Redox Potential of HydC from Thermotoga maritima. AB - Iron-sulfur clusters form one of the largest and most diverse classes of enzyme cofactors in nature. They may serve as structural factors, form electron transfer chains between active sites and external redox partners, or form components of enzyme active sites. Their specific role is a consequence of the cluster type and the surrounding protein environment. The relative effects of these factors are not completely understood, and it is not yet possible to predict the properties of iron-sulfur clusters based on amino acid sequences or rationally tune their properties to generate proteins with new desirable functions. Here, we generate mutations in a [2Fe-2S] cluster protein, the TmHydC subunit of the trimeric [FeFe]-hydrogenase from Thermotoga maritima, to study the factors that affect its redox potential. Saturation mutagenesis of Val131 was used to tune the redox potential over a 135 mV range and revealed that cluster redox potential and electronic properties correlate with amino acid hydrophobicity and the ability to form hydrogen bonds to the cluster. Proline scanning mutagenesis between pairs of ligating cysteines was used to remove backbone amide hydrogen bonds to the cluster and decrease the redox potential by up to 132 mV, without large structural changes in most cases. However, substitution of Gly83 with proline caused a change of HydC to a [4Fe-4S] cluster protein with a redox potential of 526 mV. Together, these results confirm the importance of hydrogen bonding in tuning cluster redox potentials and demonstrate the versatility of iron-sulfur cluster protein folds at binding different types of clusters. PMID- 27396838 TI - COMPARISON OF ULTRASOUND-GUIDED VS. STANDARD LANDMARK TECHNIQUES FOR TRAINING NOVICE OPERATORS IN PLACING NEEDLES INTO THE LUMBAR SUBARACHNOID SPACE OF CANINE CADAVERS. PMID- 27396839 TI - QUANTITATIVE PLANAR AND VOLUMETRIC CARDIAC MEASUREMENTS USING 64 MDCT AND 3T MRI VS. STANDARD 2D AND M-MODE ECHOCARDIOGRAPHY: DOES ANESTHETIC PROTOCOL MATTER? PMID- 27396837 TI - The role of the ITIH3 rs2535629 variant in antipsychotic response. AB - INTRODUCTION: There is mounting evidence that schizophrenia risk variants influence response to antipsychotic medication. Common single nucleotide polymorphisms (SNPs) in or near the inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) gene have been repeatedly associated with schizophrenia and related psychiatric disorders in genome-wide association studies. Here, we provide the first study to assess the relevance of the ITIH3 rs2535629 SNP in response to antipsychotic medication. METHODS: The rs2535629 SNP was genotyped in N=256 patients receiving various antipsychotics for up to 26weeks. Treatment response was assessed using the Brief Psychiatric Rating Scale (BPRS) including its positive and negative subscales. Follow-up analyses were performed after stratifying for ethnicity and medication. RESULTS: We found significant association of rs2535629 with improvement of negative symptoms in patients of European ancestry after six months of clozapine treatment (F1,87=8.8, pcorr=0.032). Patients homozygous for the minor A-allele showed the best improvement of negative BPRS scores. However, we observed no association between rs2535629 and changes in total BPRS score in the entire sample or the clozapine treated subgroup. DISCUSSION: Although there was no association of genotype with overall changes in BPRS scores, the greater improvement of negative symptoms in minor allele carriers indicates that rs2535629 may help to identify a subset of schizophrenia patients with better treatment response to clozapine. Therefore, our findings provide the first suggestive evidence that rs2535629 is relevant in antipsychotic response. PMID- 27396840 TI - Sequence effects of combined resistance exercises with step choreography in the same session in women's oxygen uptake during and postexercise. AB - The combination of step choreography (SC) with resistance training exercises (RE) in the same session is common in class fitness rooms populated mainly by women to increase energy expenditure. The aim of this study was to evaluate the differences in the exercise oxygen uptake and postexercise between two different combinations of resistance training exercises and step choreography, regarding the order of execution. Thirteen active women (30.31 +/- 4.42 years, 62.02 +/- 5.37 kg, 162.65 +/- 4.40 cm, 19.14 +/- 3.29% body fat) performed two combinations: step choreography before resistance training, where resistance training was divided into two blocks of analysis (10 min each); and step choreography divided into three equal blocks (10 min for each block), before, in the middle and after resistance exercise. There were significant differences (P<0.05) between the two sessions in oxygen uptake postexercise in the period of 0-5 min. A significant increase (P<0.0001) in the oxygen uptake absolute and relative in the heart rate between blocks 1 and 2 of resistance exercise in the two sessions was observed. In the step choreography in blocks, a significant (P = 0.001) decrease between blocks 2 and 3 in the step choreography before resistance exercise and a significant (P<0.05) increase in the heart rate in both sessions between blocks were observed. The combination of step choreography and resistance exercises during the same exercise session is a good strategy to promote an elevation of women's oxygen uptake during and after an exercise session, independent of the sequence used. PMID- 27396841 TI - Transdiagnostic versus disorder-specific internet-delivered cognitive behaviour therapy for anxiety and depression in primary care. AB - BACKGROUND: Disorder-specific and transdiagnostic internet cognitive behaviour therapy (iCBT) programs are effective for anxiety and depression, but no studies have compared their effectiveness in primary care. METHODS: Patient characteristics, adherence and effectiveness of Transdiagnostic iCBT (n=1005) were compared to disorder-specific programs for generalized anxiety disorder (GAD) (n=738) and depression (n=366) in a naturalistic non-randomised comparison study. Patients completed their iCBT program in primary care. The PHQ-9 (depression), GAD-7 (generalized anxiety), K-10 (distress), and the WHODAS-II (disability) were measured at pre- and post-treatment. RESULTS: Patients in the Transdiagnostic program had higher comorbidity rates and baseline distress. All programs were associated with medium to large within-group effect sizes for improving anxiety, depression and distress between pre- and post-treatment (d's=0.64-1.39). Controlling for baseline group differences in severity, we found small effect sizes favoring the Transdiagnostic program over the GAD program in reducing PHQ-9 (d=0.44, 95%CI: 0.34-0.53), K-10 (d=0.21, 95%CI: 0.16-0.35) and WHODAS scores (d=0.20, 95%CI: 0.10-0.29), and small effect sizes favoring the Transdiagnostic program over the Depression program in reducing GAD-7 scores (d=0.48, 95%CI: 0.36-0.60). A smaller proportion of patients completed the Transdiagnostic program (44.9%) compared to the depression (51.6%) and GAD (49.2%) programs, which was attributable to baseline differences in age and symptom severity. CONCLUSIONS: Both Transdiagnostic iCBT and disorder-specific iCBT programs are effective in primary care, but there appears to be small effects favoring Transdiagnostic iCBT. Methods to increase adherence are needed to optimize the benefits to patients, and these findings await replication in a RCT. PMID- 27396842 TI - A plea for developmental motor screening in Canadian infants. AB - Motor delays during infancy may be the first observable sign of a specific neurodevelopmental disability or of more global developmental delays. The earlier such disorders are identified, the sooner these infants can be referred for early intervention services. Although developmental motor screening is strongly recommended in other Western countries, Canada has yet to provide a developmental surveillance and screening program. Ideally, screening for motor disabilities should occur as part of the 12-month well-baby visit. In advance of that visit, parents can be provided with a parent-screening questionnaire that they can complete and bring with them to their 12-month office visit. Interpretation of the parent-completed questionnaire takes only 2 min to 3 min of the health care professional's time and, based on the results, can either reassure parents that their infant is developing typically, or lead to a referral for standardized motor screening or assessment by a paediatric physical or occupational therapist. PMID- 27396844 TI - Coming in postgraduate medicine. PMID- 27396843 TI - Hepatitis B virus dampens autophagy maturation via negative regulation of Rab7 expression. AB - Hepatitis B virus (HBV) infection brings a huge challenge for medical health practitioners. It has been reported that invaded HBV escapes autophagic degradation through inhibiting lysosome maturation following enhanced autophagy formation, which putatively contributes to HBV replication and infection. However, the underlying mechanism by which HBV escapes from autophagic degradation remains elusive. In this study, we monitored the autophagic process using HepG2 cells and mice without or with transient HBV DNA plasmid transfection (pHepG2) or stable HBV infection (HepG2.2.15 cells) in vitro and in vivo. The results of Western blot, transmission electron microscopy and confocal microscopy, confirmed that HBV induced autophagy, while the fusion of autophagosomes with lysosomes was arrested. Furthermore, Rab7, a small GTPase that functions as a molecular switch responsible for the autophagosome-lysosome fusion, was inhibited, suggesting a potential mechanism for HBV-induced inhibition of autophagic degradation. In conclusion, our study proposes a potential mechanism for how HBV escapes autophagic degradation, which might be a novel therapeutic target for controlling HBV infection. PMID- 27396845 TI - From the Editor in Chief. PMID- 27396846 TI - Problems/Solutions. PMID- 27396847 TI - Audiovisuals. PMID- 27396848 TI - What's Happening in Medicine! PMID- 27396849 TI - Washington Report on Health. PMID- 27396850 TI - Meetings & courses. PMID- 27396854 TI - Unveiling the adsorption mechanism of zeolitic imidazolate framework-8 with high efficiency for removal of copper ions from aqueous solutions. AB - Among the heavy metal ions, copper(ii) can cause eye and liver damage at high uptake. The existence of copper ions (Cu(2+)) even with an ultralow concentration of less than 0.1 MUg g(-1) can be toxic to living organisms. Thus, it is highly desirable to develop efficient adsorbents to remove Cu(2+) from aqueous solutions. In this work, without any surface functionalization or pretreatment, a water-stable zeolitic imidazolate framework (ZIF-8) synthesized at room temperature is directly used as a highly efficient adsorbent for removal of copper ions from aqueous solutions. To experimentally unveil the adsorption mechanism of Cu(2+) by using ZIF-8, we explore various effects from a series of important factors, such as pH value, contact time, temperature and initial Cu(2+) concentration. As a result, ZIF-8 nanocrystals demonstrate an unexpected high adsorption capacity of Cu(2+) and high removal efficiency for both high and low concentrations of Cu(2+) from water. Moreover, ZIF-8 nanocrystals possess fast kinetics for removing Cu(2+) with the adsorption time of less than 30 min. In addition, the pH of the solution ranging from 3 to 6 shows little effect on the adsorption of Cu(2+) by ZIF-8. The adsorption mechanism is proposed for the first time and systematically verified by various characterization techniques, such as TEM, FTIR, XPS, XRD and SEM. PMID- 27396853 TI - Human amnion favours tissue repair by inducing the M1-to-M2 switch and enhancing M2 macrophage features. AB - Human amniotic mesenchymal cells (hAMTCs) possess interesting immunomodulatory properties, making them attractive candidates for regenerative medicine applications. Recent in vivo reports argue in favour of an important role for macrophages as targets of hAMTC-mediated suppression of inflammation and the enhancement of tissue repair. However, a comprehensive study of the effects of hAMTCs and their conditioned medium (CM) on human macrophage differentiation and function is unavailable. In the present study we found that hAMTCs and CM induce the differentiation of myeloid cells (U937 and monocytes) towards macrophages. We then investigated their effects on monocytes differentiated toward pro inflammatory M1 and anti-inflammatory M2 macrophages. Monocytes treated under M1 conditions in the presence of hAMTCs or CMs shifted towards M2-like macrophages, which expressed CD14, CD209, CD23, CD163 and PM-2 K, possessed higher phagocytic activity and produced higher IL-10 and lower pro-inflammatory cytokines. They were also poor T cell stimulators and Th1 inducers, while they were able to increase activated and naive suppressive Treg subsets. We show that prostaglandins, and not IL-6, play a role in determining the M2 activation status. Instead, monocytes treated under M2 conditions in the presence of hAMTCs or CM retained M2-like features, but with an enhanced anti-inflammatory profile, having a reduced expression of the co-stimulatory molecule CD80, reduced phagocytosis activity and decreased the secretion of inflammatory chemokines. Importantly, we provide evidence that macrophages re-educated by CM improve tissue regeneration/repair in wound-healing models. In conclusion, we identified new cell targets of hAMTCs and their bioactive factors and here provide insight into the beneficial effects observed when these cells are used in therapeutic approaches in vivo. (c) 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. PMID- 27396855 TI - Knowledge, advice and attitudes toward women driving a car after caesarean section or hysterectomy: A survey of obstetrician/gynaecologists and midwives. AB - BACKGROUND: Women are given variable information about when to recommence driving after surgery. AIMS: To assess obstetrician/gynaecologists' and midwives' knowledge, attitudes and advice about car driving after abdominal surgery including hysterectomy or caesarean section (CS). MATERIALS AND METHODS: An anonymous SurveyMonkeyTM survey was distributed to accredited trainees and Fellows of the Royal Australian New Zealand College of Obstetricians and Gynaecologists and midwives registered with the Australian College of Midwives by email in November 2013. Demographic information, recommendations about driving, and reasoning behind these recommendations were collected. RESULTS: Nine hundred and seventy-seven clinician responses (15.8%) were analysed: 555 midwives, 92 trainees and 330 Fellows. Ninety-six percent gave advice about driving after surgery. Respondents considered pain (85.6%), medication (73.2%) and mobility (70.5%) the most important factors when advising on resumption of driving. After uncomplicated CS, 19% said they would advise a well woman that she could drive <4 weeks, 18% advised four weeks, 33% advised five to six weeks and 27% did not give a specific timeframe. Similar timeframes were given following hysterectomy. Of each professional group, trainees (49%) and midwives (48%) were more likely to advise waiting five to six weeks to resume driving compared with Fellows (9%) (P < 0.001). Although 71.5% of respondents thought that most women drove before four weeks, only 33.9% of respondents thought driving earlier than advice given was unsafe. CONCLUSIONS: Clinicians frequently give advice about driving after surgery. This advice is inconsistent and many advise women not to drive for significant time periods. This study highlights the need for education and research about driving after surgery. PMID- 27396857 TI - Revisiting the cost of carnivory in mammals. AB - Predator-prey relationships play a key role in the evolution and ecology of carnivores. An understanding of predator-prey relationships and how this differs across species and environments provides information on how carnivorous strategies have evolved and how they may change in response to environmental change. We aim to determine how mammals overcame the challenges of living within the marine environment; specifically, how this altered predator-prey body mass relationships relative to terrestrial mammals. Using predator and prey mass data collected from the literature, we applied phylogenetic piecewise regressions to investigate the relationship between predator and prey size across carnivorous mammals (51 terrestrial and 56 marine mammals). We demonstrate that carnivorous mammals have four broad dietary groups: small marine carnivores (< 11 000 kg) and small terrestrial carnivores (< 11 kg) feed on prey less than 5 kg and 2 kg, respectively. On average, large marine carnivores (> 11 000 kg) feed on prey equal to 0.01% of the carnivore's body size, compared to 45% or greater in large terrestrial carnivores (> 11 kg). We propose that differences in prey availability, and the relative ease of processing large prey in the terrestrial environment and small prey in marine environment, have led to the evolution of these novel foraging behaviours. Our results provide important insights into the selection pressures that may have been faced by early marine mammals and ultimately led to the evolution of a range of feeding strategies and predatory behaviours. PMID- 27396856 TI - Hypoxanthine induces cholesterol accumulation and incites atherosclerosis in apolipoprotein E-deficient mice and cells. AB - Reactive oxygen species (ROS) generation during purine metabolism is associated with xanthine oxidase and uric acid. However, the direct effect of hypoxanthine on ROS generation and atherosclerosis has not been evaluated. Smoking and heavy drinking are associated with elevated levels of hypoxanthine. In this study, we investigated the role of hypoxanthine on cholesterol synthesis and atherosclerosis development, particularly in apolipoprotein E (APOE)-deficient mice. The effect of hypoxanthine on the regulation of cholesterol synthesis and atherosclerosis were evaluated in Apoe knockout (KO) mice and cultured HepG2 cells. Hypoxanthine markedly increased serum cholesterol levels and the atherosclerotic plaque area in Apoe KO mice. In HepG2 cells, hypoxanthine increased intracellular ROS production. Hypoxanthine increased cholesterol accumulation and decreased APOE and ATP-binding cassette transporter A1 (ABCA1) mRNA and protein expression in HepG2 cells. Furthermore, H2 O2 also increased cholesterol accumulation and decreased APOE and ABCA1 expression. This effect was partially reversible by treatment with the antioxidant N-acetyl cysteine and allopurinol. Hypoxanthine and APOE knockdown using APOE-siRNA synergistically induced cholesterol accumulation and reduced APOE and ABCA1 expression. Hypoxanthine induces cholesterol accumulation in hepatic cells through alterations in enzymes that control lipid transport and induces atherosclerosis in APOE-deficient cells and mice. These effects are partially mediated through ROS produced in response to hypoxanthine. PMID- 27396858 TI - Electron-Rotor Interaction in Organic-Inorganic Lead Iodide Perovskites Discovered by Isotope Effects. AB - We report on the carrier-rotor coupling effect in perovskite organic-inorganic hybrid lead iodide (CH3NH3PbI3) compounds discovered by isotope effects. Deuterated organic-inorganic perovskite compounds including CH3ND3PbI3, CD3NH3PbI3, and CD3ND3PbI3 were synthesized. Devices made from regular CH3NH3PbI3 and deuterated CH3ND3PbI3 exhibit comparable performance in band gap, current voltage, carrier mobility, and power conversion efficiency. However, a time resolved photoluminescence (TRPL) study reveals that CH3NH3PbI3 exhibits notably longer carrier lifetime than that of CH3ND3PbI3, in both thin-film and single crystal formats. Furthermore, the comparison in carrier lifetime between CD3NH3PbI3 and CH3ND3PbI3 single crystals suggests that vibrational modes in methylammonium (MA(+)) have little impact on carrier lifetime. In contrast, the fully deuterated compound CD3ND3PbI3 reconfirmed the trend of decreasing carrier lifetime upon the increasing moment of inertia of cationic MA(+). Polaron model elucidates the electron-rotor interaction. PMID- 27396859 TI - Treating and preventing dysphagia in the community. PMID- 27396860 TI - Identifying and managing malnutrition in the community. AB - Malnutrition affects more than 3 million people in the UK, most of whom live in the community. Malnutrition is both a cause and consequence of disease and can lead to increased mortality and morbidity, delayed recovery from illness and impaired body function which can make carrying out activities of daily living difficult. Managing malnutrition in the community involves identifying malnutrition using a universally validated screening tool and implementing appropriate care plans according to the degree of malnutrition. Regional and local guidance can be used to assist healthcare professionals to prescribe appropriate oral nutritional supplements and monitor nutritional aims and goals. PMID- 27396861 TI - Innovations to support hydration care across health and social care. AB - It is known that the primary cause of dehydration in elderly care is caused by a person not regularly drinking enough. Dehydration is a much-publicised national concern, associated with poor outcomes of care and acute hospital admissions. However, in November last year, NHS England stated that the scale of dehydration is not known; in comparison, it confirmed at least three million people are at risk of malnutrition. The stark comparison in information occurs because there is no nationally recognised screening tool to identify who is at risk of dehydration. An innovative nursing role, focused on finding solutions to reduce the risk of dehydration in the care of older and vulnerable persons, has led to the development of a simple dehydration screening tool called 'ROC to drink' (ROC stands for 'reliance on a carer'), which focuses on the level of support needed to drink. An innovative tea cup has been designed to help raise standards for monitoring drinks and raise awareness about intake. PMID- 27396862 TI - Nasogastric tube feeding: a safe option for patients? AB - This article will show that fine-bore nasogastric tube feeding can be facilitated for patients when long term percutaneous endoscopic gastrostomy (PEG) or radiologically inserted gastrostomy (RIG) options are not suitable. How the safe replacement of these tubes is facilitated, and what instructions the patient and the nursing home are given to support patient care and safety are also discussed. The decision to support this type of feeding must be completely individualised, considering home and external support agencies available to each patient. The risk assessment completed to facilitate this has been based on the patients' individual circumstances, and a nasogastric tube home passport developed to help in the assessment and decision-making process. For fine-bore nasogastric tube feeding to be safe, it does have to be supported once the patient is discharged from the hospital. A good knowledge of the home support and carer support agencies, and what is available, should be discussed. Multidisciplinary team support is essential in ensuring a safe discharge can be planned and managed. Good patient risk assessment and nursing considerations are discussed to show how the challenges that may prevent a patient discharge with this type of feed are managed. This article will show how two very different patients discharges were facilitated by safe fine-bore nasogastric tube feeding in the community. Patient assessment and nursing considerations are discussed, as well as the importance of a multidisciplinary approach to show how this was successfully achieved in a local district hospital. PMID- 27396863 TI - Interview with Grace Burfield. PMID- 27396864 TI - Celebrating 30 years of improving patient care. PMID- 27396865 TI - ENFit: a major patient safety breakthrough. PMID- 27396867 TI - A1. Volume load and pressure load both relate to relative wall thickness in former PE. AB - AIMS: To study the relationship between volume and pressure load on the one hand and relative wall thickness (RWT) on the other hand in former preeclamptic women. METHODS: In 654 former PE women, blood pressure (BP) and PV (iodine 125 albumin indicator dilution technique) where measured. PV was indexed for body surface area (BSA). Echocardiography was performed to calculate RWT. The study population was divided in 4 subgroups consisting of women with either normal- or high systolic BP (sysBP) (<140 versus >=140mmHg, respectively) and normal- or low-PV index (>1373 versus <=1373 ml/m2 respectively). Differences between the four subgroups where analyzed with ANOVA. Pearson's rho is calculated for the correlation between PV and sysBP on the one hand and RWT on the other hand. RESULTS: RWT was the lowest in the group with normal sysBP and normal PV and the highest in the subgroup with high sysBP and low PV subgroup (Table 1). Moreover, PVindex correlated negatively with RWT in the setting of both normal sysBP and high sysBP (Figure 1a and b) while systolic BP correlated positively with RWT in the setting of normal sysBP but not in the setting of high sysBP (Figure 1c and d). DISCUSSION: Raised RWT, as a measure for concentric remodelling, relates to both decreased volume load and increased pressure load. PMID- 27396868 TI - Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. AB - OBJECTIVE: l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. METHODS: Subjects were 20 patients with MDD (four males; mean age: 41.0+/-14.1 years, 16 females; 42.9+/ 12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). RESULTS: HAMD-21 score was reduced after l theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. CONCLUSION: Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects. PMID- 27396869 TI - Home literacy environment profiles of children with language impairment: associations with caregiver- and child-specific factors. AB - BACKGROUND: Numerous studies suggest a positive relationship between the home literacy environment (HLE) and children's language and literacy skills, yet very little research has focused on the HLE of children with language impairment (LI). Children with LI are at risk for reading difficulties; thus, understanding the nature and frequency of their home literacy interactions is warranted. AIMS: To identify unique HLE profiles within a large sample of children with LI, and to determine relevant caregiver- and child-specific factors that predict children's profile membership. METHODS & PROCEDURES: Participants were 195 kindergarten and first-grade children with LI who were receiving school-based language therapy. Caregivers completed a comprehensive questionnaire regarding their child's HLE, and the extent to which their child engaged in shared book reading, were taught about letters, initiated or asked to be read to, and chose to read independently. Caregivers also answered questions regarding the highest level of maternal education, caregiver history of reading difficulties, and caregiver reading habits. Children completed a language and literacy battery in the fall of their academic year. OUTCOMES & RESULTS: Latent profile analyses indicated a three profile solution, representing high, average and low frequency of the selected HLE indicators. Multinomial regression further revealed that caregivers' own reading habits influenced children's profile membership, as did child age and language abilities. CONCLUSIONS & IMPLICATIONS: These results highlight the considerable variability in the frequency of home literacy interactions of children with LI. Future work examining relations between familial reading practices and literacy outcomes for children with LI is warranted. PMID- 27396871 TI - A label-free and enzyme-free system for operating various logic devices using poly(thymine)-templated CuNPs and SYBR Green I as signal transducers. AB - For the first time by integrating fluorescent polyT-templated CuNPs and SYBR Green I, a basic INHIBIT gate and four advanced logic circuits (2-to-1 encoder, 4 to-2 encoder, 1-to-2 decoder and 1-to-2 demultiplexer) have been conceptually realized under label-free and enzyme-free conditions. Taking advantage of the selective formation of CuNPs on ss-DNA, the implementation of these advanced logic devices were achieved without any usage of dye quenching groups or other nanomaterials like graphene oxide or AuNPs since polyA strands not only worked as an input but also acted as effective inhibitors towards polyT templates, meeting the aim of developing bio-computing with cost-effective and operationally simple methods. In short, polyT-templated CuNPs, as promising fluorescent signal reporters, are successfully applied to fabricate advanced logic devices, which may present a potential path for future development of molecular computations. PMID- 27396870 TI - Three Novel Alkaloids from Portulaca oleracea L. and Their Anti-inflammatory Effects. AB - Three novel carbon skeleton alkaloids, named oleracimine (1), oleracimine A (2), and oleracone A (3), with one novel azulene carbon skeleton compound, oleracone B (4), and one known compound, beta-carboline (5), were first isolated from Portulaca oleracea L. The structures were determined using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance and high-resolution electrospray ionization time-of-flight mass spectrometry techniques. In addition, oleracimine (1) was used to investigate the anti-inflammatory effects on lipopolysaccharide-stimulated macrophages. The results of enzyme-linked immunosorbent assay, western blot, and real-time polymerase chain reaction showed that oleracimine (1) remarkably inhibited nitric oxide production and could dose dependently decrease the secretions of interleukin 6, tumor necrosis factor alpha, nitric oxide, and prostaglandin E2 in cell culture supernatants as well as the mRNA of cyclooxygenase-2 and inducible nitric oxide synthase. PMID- 27396872 TI - Correction: The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct. AB - Correction for 'The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct' by In-Hu Choe, et al., Food Funct., 2016, 7, 2557-2565. PMID- 27396873 TI - Angiotensin II acting on PVN induces sympathoexcitation and pressor responses via the PI3K-dependent pathway. AB - In vitro studies have shown that angiotensin II (ANG II), via activation of ANG II type 1 (AT1) receptor plays an important role on the neural control of the blood pressure (BP), through an intracellular signalling pathway involving PI3K in the paraventricular nucleus of the hypothalamus (PVN). However, to the best of our knowledge, no in vivo study has been performed yet to unravel the functional role of ANG II and its interaction with PI3K pathways in the neural control of circulation of non-anesthetized animals. Here, we demonstrate that exogenous ANG II microinjected into the PVN in anaesthetic-free animals evokes an increase in sympathetic nerve activity and BP in a PI3K-dependent manner. PMID- 27396875 TI - Effects of Metal Ions and pH on the Stability of Linoleic Acid Hydroperoxide in the Water Phase. AB - We examined linoleic acid hydroperoxide (hydroperoxyoctadecadienoic acid; HPOD) decomposition kinetically with or without various metal ions and at various pHs as effective factors on the stability of hydroperoxides. HPOD decomposition in the reaction system of this experiment was a first-order reaction. Manganese, copper, and especially iron accelerated the decomposition of HPOD, while lithium, sodium, potassium, magnesium, calcium, and aluminium stabilized HPOD. Besides, HPOD was comparatively stable at pH 3, 7, and 8, and unstable at pH 2, 4-6, and 9. According to activation energy, however, it was estimated that only in the reaction system with iron or at pH 2 and 9 the HPOD decomposition mechanism was different from that in water. PMID- 27396876 TI - Synthesis of Didocosahexaenoylphosphatidylserine. AB - 1,2-Di-O-isopropylideneglycerophosphorochloridate prepared from isopropylindene glycerol and phosphorus oxychloride, was allowed to react with Z-l-serine-N phthalimidomethyl ester to obtain a derivative of phosphatidylserine. Then, after the isopropylidene group was removed by Amberlite IR-120 (H(+)), and the phosphate group was also blocked as a Ba-salt, this derivative was coupled with docosahexaenoic acid, applying the method of activated ester. Removal of both protective groups of serine was finally done by dry hydrogen chloride in chloroform. PMID- 27396874 TI - Cardiac vagal preganglionic neurones: An update. AB - The autonomic nervous system controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic and sympathetic activities. These activities are generated by groups of sympathoexcitatory and vagal preganglionic neurones residing in a close proximity to each other within well-defined structures of the brainstem. This short essay provides a general overview and an update on the latest developments in our understanding of the central nervous origins and functional significance of cardiac vagal tone. Significant experimental evidence suggests that distinct groups of cardiac vagal preganglionic neurones with different patterns of activity control nodal tissue (controlling the heart rate and atrioventricular conductance) and the ventricular myocardium (modulating its contractility and excitability). PMID- 27396877 TI - Transxylosylation of beta-Xylosidase from Aspergillus awamori K4. AB - beta-Xylosidase from Aspergillus awamori K4 was purified. The optimum pH and temperature were around pH 4 and 70 degrees C, and the molecular weight was estimated to be 117,000 on SDS-PAGE analysis. The enzyme has broad acceptor specificity in transxylosylation. Especially, its acceptor accessibility for sorbitol and mannitol of sugar alcohols were higher than that for monosaccharides. Trehalose was a much more effective acceptor than maltose and lactose of other disaccharides. In the reaction with 13-14% xylooligosaccharides (consisting of 3.4% xylose, 67.9% xylobiose, and 28.7% xylotriose) and 9-13% acceptors (sorbitol, mannitol, and trehalose), the amount of transfer products for each acceptor was 7-11% in 24 h. On (1)H- and (13)C-NMR analysis, main transfer products with sorbitol and mannitol were 6-O-beta-xylosyl sorbitol (77.3%) and l(6)-O-beta-xylosyl mannitol (73.7%), respectively. Two products with trehalose were 6 (6')-O-beta-xylosyl trehalose (52.1%) and 6,6'-O-beta-di-xylosyl trehalose (47.9%). PMID- 27396878 TI - New Physiological Effects of 5-Aminolevulinic Acid in Plants: The Increase of Photosynthesis, Chlorophyll Content, and Plant Growth. AB - 5-Aminolevulinic acid (ALA) promoted the growth and yield of several crops and vegetables at concentrations lower than those eliciting herbicidal responses, i.e., less than 1.8 mm by foliar spray and 60 MUm by root soaking. To evaluate the physiological action of ALA, the effects of ALA on plants were examined by several bioassay systems at 0.0006-600 MUm. ALA at 0.06-6 MUm by root soaking increased the growth of rice seedlings in light, but did not affect this in darkness. In horseradish shoot primordia, promotion by ALA was not proportional among total chlorophyll content, chlorophyll concentration, and fresh weight. In the test using pothos, ALA at 0.06 MUm elicited the accumulation of chlorophyll, but the photosynthesis of the plants was promoted by treatment together with ALA and nutrients. These results suggest that ALA have a variety of plant physiological effects on chlorophyll synthesis, photosynthesis, and plant growth, and ALA acts as a growth regulator in plants at low concentrations. These effects of ALA were also assumed to be linked to light irradiation and an uptake of fertilizer by plants. However, excess ALA suppressed these effects. PMID- 27396879 TI - Continuous Production of l-Alanine with NADH Regeneration by a Nanofiltration Membrane Reactor. AB - A conjugated enzyme system, alanine dehydrogenase (AIDH) for stereospecific reduction of pyruvate to l-alanine and glucose dehydrogenase (GDH) for regeneration of NADH, were coimmobilized in a nanofiltration membrane bioreactor (NFMBR) for the continuous production of l-alanine from pyruvate with NADH regeneration. Since pyruvate was proved to be unstable at neutral pH, it was kept under acidic conditions and supplied to NFMBR separately from the other substrates. As 0.2 m pyruvate in HCl solution (pH 4), 10 mm NAD, 0.2 m glucose, and 0.2 m NH4Cl in 0.5 m Tris buffer (pH 8) were continuously supplied to NFMBR with immobilized AIDH (100 U/ml) and GDH (140 U/ml) at the retention time of 80 min, the maximum conversion, reactor productivity, and NAD regeneration number were 100%, 320 g/liter/d, and 20,000, respectively. To avoid the effect of pyruvate instability, a consecutive reaction system, lactate dehydrogenase (l LDH) and AIDH, was also used. In this system, the l-LDH provides pyruvate, the substrate for the AIDH reaction, from l-lactate regenerating NADH simultaneously, so the pyruvate could be consumed as soon as it was produced. As 0.2 m l-lactate, 10 mm NAD, 0.2 m NH4Cl in 0.5 m Tris buffer (pH 8) were continuously supplied to NFMBR with immobilized l-LDH (100 U/ml) and AIDH (100 U/ml) at the retention time of 160 min, the maximum conversion, reactor productivity, and the NAD regeneration number were 100%, 160 g/Iiter/d, and 20,000, respectively. PMID- 27396880 TI - Superoxide Dismutase Inhibition of Oxidation of Ubiquinol and Concomitant Formation of Hydrogen Peroxide. AB - We measured ubiquinone (CoQ0) and hydrogen peroxide (H2O2) formed in the process of oxidation of ubiquinol (CoQ0H2). We found that copper-zinc superoxide dismutase and manganese superoxide dismutase inhibited both the CoQ0 formation and the H2O2 formation only in the presence of chelators such as DTPA (diethylenetriaminepentaacetic acid). The amount of H2O2 was almost equal to that of CoQ0, indicating that the H2O2 formation was coupled with the CoQ0 formation. The lack of inhibitory effects of the corresponding heat-inactivated superoxide dismutase (SOD) confirmed that the inhibition by the original SOD was due to its enzymatic activity. We propose that CoQ0H2 oxidation occurs as a chain reaction with superoxide as the chain carrier and that SOD inhibits this reaction by lowering the superoxide concentration. PMID- 27396881 TI - Synthesis and Biological Activities of 8'-Methylene- and 8'-Methylidyneabscisic Acids. AB - 8'-Methylene- and 8'-methylidyneabscisic acids which might act as suicide inhibitors of the 8'-hydroxylase of abscisic acid, were designed, synthesized, and optically resolved. The (+)-isomers showed stronger inhibitory activity in rice elongation and in lettuce seed germination than (+)-abscisic acid. The activity of (+)-8'-methylidyneabscisic acid was the strongest of the analogues synthesized to date, 40-fold stronger than abscisic acid. PMID- 27396882 TI - Characterization of Styrene Oxide Isomerase, a Key Enzyme of Styrene and Styrene Oxide Metabolism in Corynehacterium sp. AB - Styrene oxide isomerase (SOI) [EC 5.3.99.7], most probably located in the cell wall, was partially purified from Coiynebacterium sp. AC-5 cells grown in a styrene gas atmospheres. The enzyme catalyzed the isomerization reaction to give phenylacetaldehyde, but did not catalyze its reverse reaction. The optimum pH of the reaction was around 7.0, and the enzyme was unstable below pH 6.0. The Km toward styrene oxide was very low (7.7 * 10(-5) m), indicating its high affinity for styrene oxide. The enzyme showed strict substrate specificity, and epoxide compounds other than styrene oxide did not serve as substrates. (S)-Styrene oxide was preferentially converted by the enzyme, compared with the (R)-isomer. The possible application of SOI as a biocatalyst is also discussed. PMID- 27396883 TI - Glycogen-Surfactant Complexes: Phase Behavior in a Water/Phytoglycogen/Sodium Dodecyl Sulfate (SDS) System. AB - The phase behavior was investigated in water/phytoglycogen/SDS and C12EO20 systems. It was found that phytoglycogen was precipitated in the presence of these surfactants. Phytoglycogen in the SDS system was dispersed more homogeneously than in the C12EO20 system, and a liquid-liquid phase separation region appeared in the SDS system. In the C12EO20 system, the transmittance of a stirred solution in the single-phase region was slightly lower than that of the phytoglycogen controls, whereas the transmittance of the stirred solution was higher than that of the controls in the SDS system. It thus seems that phytoglycogen formed a complex with SDS and that this complex affected the transmittance in the single-phase region. Viscosity measurements of the aqueous solution supported the existence of such a phytoglycogen-SDS complex. These results enabled us to propose a schematic representation of the complex structure. It was clarified that phytoglycogen forms a complex with SDS, and that the structure of the complex modifies the dispersion stability of phytoglycogen. PMID- 27396884 TI - Autoxidation Reaction Mechanism for l-Ascorbic Acid in Methanol without Metal Ion Catalysis. AB - The autoxidation reaction of l-ascorbic acid (ASA) in methanol without metal ion catalysis was studied. Besides l-threonolactone (THL) and oxalic acid (OXA), methyl l-threonate, and threonic acid were identified as initial autoxidation products of ASA, which were the C(2)-C(3) fission product via the C(2) oxygen adduct of ASA. This pathway is different from the one via dehydro-l-ASA (DASA), which has long been believed to be the only oxidation pathway of ASA. It was confirmed that this reaction also occurred in both water and other polar solvents, including methanol. It was clarified that mono-dissociated ASA was more reactive than the non-dissociated ASA in this pathway, and that the main reaction products formed from these two forms of ASA were also somewhat different. Determination of the amount of remaining ASA and the yields of THL and OXA, C(2) C(3) fission products, and of DASA were carried out doing the autoxidation of ASA under various reaction conditions. PMID- 27396885 TI - Effect of Polyphenol Oxidase on Deodorization. AB - A mixture of purified polyphenol oxidases (PPO), or acetone powders prepared from fruits and vegetables, and polyphenolic compounds (PPs) totally eliminated a methylmercaptan odor. 2-Methyl-thiochlorogenic acid was isolated from the reaction mixture of methylmercaptan and chlorogenic acid with burdock acetone powder. Further, the formation of 5-methylthiochlorogenic acid and 2,5 bis(methylthio)-chlorogenic acid was suggested. These facts demonstrate that the o-quinone compounds formed from o-diphenols by PPO rapidly reacted with methylmercaptan. The oxidation reaction of PPs by using acetone powder containing PPO or peroxidase is considered to be more effective for removing bad smells from our mouths and from the environment. PMID- 27396886 TI - Purification and Some Properties of a Protease from the Sarcocarp of Musk Melon Fruit. AB - A protease has been purified from sarcocarp of musk melon, Cucumis melo ssp. melo var. reticulatus Naud. Earl's Favourite. The protease was mostly present in the placenta part of the fruit and next in the inside mesocarp. The molecular mass of the enzyme was estimated to be about 62kDa on SDS-PAGE. The enzyme had a carbohydrate moiety. The optimum pH of the enzyme was 11 at 35 degrees C using casein as a substrate. The enzyme was stable between pH 6 and 11. The enzyme was strongly inhibited by diisopropyl fluorophosphate, but was not inhibited by EDTA or cysteine protease inhibitors. From the digestion of Ala-Ala-Pro-X-pNA (X = Phe, Leu, Val, Ala, Gly, Lys, Glu, Pro, and diaminopropionic acid (Dap) substrates the specificity of the protease was found to be approximately broad, but the preferential cleavage sites were C-terminal sites of hydrophobic or acidic amino acid residues at P, position. It was proved that the enzymatic properties of musk melon protease are similar to those of cucumisin [EC 3.4.21.25]. The enzyme was not inhibited by typical proteinous inhibitors such as STI or ovomucoid. Therefore, this enzyme seems to be a useful protease for the food industries. PMID- 27396887 TI - Synthesis and Fungicidal Activity of 6-Alkyl Six-membered Cyclic Thiophosphates. AB - Synthesis and fungicidal activities of new 6-aIkyl six-membered cyclic phosphates were examined. Ten kinds of 6-alkyl six-membered cyclic thiophosphates were synthesized by reaction with 5-alkyl-2-hydroxybenzyl alcohols and phosphoric agents. Among the prepared compounds, 2-ethoxy-6-elhyl-4H-1,3,2 benzodioxaphosphorin 2-sulfide (1) had activity as potent as the commercial fungicide iprobenfos against Pythium sp. and Corticium rolfsii at 10ppm. PMID- 27396888 TI - Superoxide-scavenging and Tyrosinase-inhibitory Activities of the Extracts of Some Chinese Medicines. AB - The superoxide-scavenging and the tyrosinase-inhibitory activities of 28 kinds of plants used as Chinese medicines were evaluated. Methanol/water extracts were used for the screening tests, and for those which represented high activities, other kinds of extracts were also studied. The extracts of Mallotus japonicus Muell. Arg. scavenged superoxide strongly; the half-inhibiting concentration (IC50) of its 50% methanol/water extract was 10.57 MUg of dried material in 1 ml of reaction mixture. The extracts of Fntillaria thunbergii Miq., Carthamus tinctorius L., and Prunus persica (L.) Batsch had strong tyrosinase-inhibitory activities, and the extracts of Scutellariu baicalensis Georgi represented both kinds of activities. These facts suggested that Chinese medicines may be a treasure house of chemical compounds that have the superoxide-scavenging and the tyrosinase-inhibitory activities. PMID- 27396889 TI - Formation of Thioxopyrrolidines and Dithiocarbamates from 4-Methylthio-3-butenyl Isothiocyanates, the Pungent Principle of Radish, in Aqueous Media. AB - Reaction products of 4-methylthio-3-butenyl isothiocyanate (MTBI), the radish pungent principle, in aqueous media were identified and their antimicrobial activities were examined. A rapid degradation of MTBI in aqueous media afforded a mixture of 3-(hydroxy)methylene-2-thioxopyrrolidine (1), (Z)-3-(methylthio) methylene-2-thioxopyrrolidine (2), its (E)-isomer (3), methyl 4 methylthiobutyldithiocarbamate (4), methyl (Z)-4-methylthio-3 butenyldithiocarbarnaie (5), and its (E)-isomer (6). The products 1, 2, and 3 were detected at all pHs examined, while 4, 5, and 6 were formed at pH over 6.0. The formation of 4 from 6 was accompanied by an oxidation of methanethiol released from MTBI in aqueous media. Antimicrobial activities of 2 and 3 against all microbes examined were much lower than that of 1, which had MICs ranging from 50 to 400 MUg/ml. As for 4, 5, and 6, antifungal activities were comparable to that of 1, but little antibacterial activities were observed. The antimicrobial activities of the six products were considered to be far lower than that of MTBI. PMID- 27396890 TI - Eicosanyl p-Coumarates from a Kenyan Plant, Psiadia punctulata: Plant Growth Inhibitors. AB - From methanol extracts of fresh leaves of Psiadia punctulata (DC.) Vatke, lettuce seed radicle growth inhibitors were isolated and identified as E- and Z-eicosanyl p-coumarates by spectroscopic analyses. PMID- 27396891 TI - Production of New Restriction Endonuclease VpaK111BI Recognizing Sequence 5' GGWCC-3' in a Haemolysin-less Mutant of Vibrio parahaemolyticus. AB - High restriction endonuclease activity was found in a haemolysin-less mutant of the Vibrio parahaemolyticus 1743-1 strain. The endonuclease, named VpaK11BI, recognized the palindromic pentanucleotide sequence of 5'-GGWCC-3' and cleaved double-stranded DNA after the first G, which is exactly the same as the specificity of AvaII. The haemolysin-less mutant of V. parahaemolyticus is now available for producing the valuable restriction endonuclease on a commercial scale. PMID- 27396892 TI - Conversion from Tryptophan Precursor into Violacein Pigments by a Cell-free System from Chromobacterium violaceum. AB - A cell-free system for converting tryptophan precursor into violacein pigments is reported. Crucial factors were the requirements of the reduced nicotinamides as a cofactor and Zn(2+) as a metal ion. Optimal pHs were in the range of 8.5-9.5. The effectiveness of NADH was thirty times lower than that of NADPH at a low concentration of 2mm. The oxygenation mechanism(s) is discussed by using oxygenase inhibitors such as amethopterin, metyrapone, ancymidol, and prohexadione. Metal-chelating agents strongly inhibited the biosynthesis, suggesting that metallo-enzymes are involved in the biosynthesis. PMID- 27396893 TI - Effects of Carnosine and Anserine on the Destruction of Vitamin B12 with Vitamin C in the Presence of Copper. AB - Vitamin B12 is destroyed by the addition of substantial amounts of vitamin C in the presence of copper. Effects of carnosine and anserine, natural water-soluble antioxidants, on the destruction of vitamin B12, were studied. Addition of carnosine (l0mM) effectively repressed the destruction of vitamin B12, but anserine had only weak inhibitory effects. PMID- 27396894 TI - Flutolanil Resistance as a Genetic Marker of Coprinus cinereus Strains. AB - All 4 Schizophyllum commune strains among several basidiomycete species were exclusively resistant to flutolanil, which inhibits succinate dehydrogenase complex (SDC) function. Flutolanil resistant strains could be screened from monokaryotic protoplasts of sensitive Coprinus cinereus, by treating them with a cloned genomic SDC iron-sulfur protein (IP) gene from the resistant S. commune. The obtained resistance was stably transferred to the progeny. PMID- 27396895 TI - Substantially Complete Removal of Three Major Allergenic Soybean Proteins (Gly m Bd 30K, Gly m Bd 28K, and the alpha-Subunit of Conglycinin) from Soy Protein by Using a Mutant Soybean, Tohoku 124. AB - A wild-type soybean contains three major allergenic proteins, Gly m Bd 30K, the alpha-subunit of conglycinin, and Gly m Bd 28K. A genetically mutated soybean (Tohoku 124), which was originally developed as a cultivar lacking the alpha- and alpha'-subunits of conglycinin, was also found to lack Gly m Bd 28K from immunoblot analysis using monoclonal antibodies specific to Gly m Bd 28K. This finding indicates the possibility to prepare soy milk and soy proteins containing none of the three major allergenic soybean proteins from this cultivar. By applying the previous removal procedure [Samoto et al., Biosci. Biotech. Biochem., 60, 1911-1913 (1996)] to Tohoku 124, the substantially complete removal of the three major allergenic proteins from the soy milk was attained. The removal rates of Gly m Bd 30K, alpha-subunit of conglycinin, and Gly m Bd 28K were 99.8, 100, and 100%, respectively. PMID- 27396896 TI - A Novel Modification of the Lysine Residue at Position 12 of Histone H4 in Starfish Sperm. AB - Post-translational modification of core histones is essential in processes requiring chromatin remodeling. We report here a novel modification in histones of the sperm of the starfish, Asterina pectinifera, which involves an epsilon (gamma-glutamyl)lysine cross-link between the glutamine residue at position 9 of histone H2B and the lysine residue at position 12 of histone H4. PMID- 27396897 TI - Simplicissin, a New Pollen Growth Inhibitor Produced by the Fungus, Penicillium cf. simplidssimum (Oudemans) Thorn No. 410. AB - A new pollen growth inhibitor, named simplicissin, was isolated from Penicillium cf. simplicissimum (Oudemans) Thorn No. 410, and its structure was established by spectroscopic methods including 2D NMR. The biological activities of the compound were examined by the bioassay methods involving tea pollen together with lettuce seedlings. The compound inhibited the growth of the tea pollen tube by 45% at a concentration of 3 mg/liter and showed complete inhibition at 10mg/liter. PMID- 27396898 TI - Cholesteric liquid crystals in rectangular microchannels: skyrmions and stripes. AB - In this paper, we present experimental and numerical studies on the microstructures of a cholesteric liquid crystal (CLC) confined in rectangular micron-channels. By using a sequence of microfabrication techniques we fabricated the micro-sized channels with accurately controlled size, aspect ratio and homeotropic surface anchoring. Through optical microscopic studies we established a phase diagram for the liquid crystal defect textures as a function of the channel depth and width. For the channel width larger than ~2 times the cholesteric pitch p, the LC molecules are oriented primarily vertical to the channel when the channel depth is below 0.75p, form bubble domain defects when the channel depth is around 0.75p, and form stripe textures when the cell depth is above the cholesteric pitch p. In addition, the bubble domain size and the stripe texture periodicity are found to grow with the increase of the channel width. For the channel width smaller than ~2p and the channel depth between 0.6p to 1.1p, no textures can be observed in the channels. Numerical simulations based on a director tensor relaxation approach yield detailed molecular director fields, and show that the bubble domain defects are baby-skyrmions and that the stripes are the first type of cholesteric fingerprints. A comparison with previous experiments and numerical simulations indicates that the size of the microchannels also influences what type of soliton-like topological textures form in the CLCs confined in the channels. PMID- 27396899 TI - Heat shock protein 22 (HSPB8) limits TGF-beta-stimulated migration of osteoblasts. AB - Heat shock proteins (HSPs) are induced in response to various physiological and environmental conditions such as chemical and heat stress, and recognized to function as molecular chaperones. HSP22 (HSPB8), a low-molecular weight HSP, is ubiquitously expressed in many cell types. However, the precise role of HSP22 in bone metabolism remains to be clarified. In the present study, we investigated whether HSP22 is implicated in the transforming growth factor-beta (TGF-beta) stimulated migration of osteoblast-like MC3T3-E1 cells. Although protein levels of HSP22 were clearly detected in unstimulated MC3T3-E1 cells, TGF-beta failed to induce the protein levels. The TGF-beta-stimulated migration was significantly up regulated by knockdown of HSP22 expression. The cell migration stimulated by platelet-derived growth factor-BB was also enhanced by HSP22 knockdown. SB203580, an inhibitor of p38 mitogen-activated protein kinase, PD98059, an inhibitor of MEK1/2, or SP600125, an inhibitor of stress-activated protein kinase/c-Jun N terminal kinase had no effects on the TGF-beta-induced migration. SIS3, a specific inhibitor of TGF-beta-dependent Smad3 phosphorylation, significantly reduced the migration with or without TGF-beta stimulation. Smad2, Smad3, Smad4 or Smad7 was not coimmunoprecipitated with HSP22. On the other hand, the TGF-beta induced Smad2 phosphorylation was enhanced by HSP22 down-regulation. The protein levels of TGF-beta type II receptor (TGF-beta RII) but not TGF-beta type I receptor (TGF-beta RI) was significantly up-regulated in HSP22 knockdown cells compared with those in the control cells. However, the levels of TGF-beta RII mRNA in HSP22 knockdown cells were little different from those of the control cells. Neither TGF-beta RI nor TGF-beta RII was coimmunoprecipitated with HSP22. SIS3 reduced the amplification by HSP22 knockdown of the TGF-beta-stimulated cell migration almost to the basal level. Our results strongly suggest that HSP22 functions as a negative regulator in the TGF-beta-stimulated migration of osteoblasts via suppression of the Smad-dependent pathway, resulting from modulating the protein levels of TGF-beta RII. PMID- 27396900 TI - From PBL tutoring to PBL coaching in undergraduate medical education: an interpretative phenomenological analysis study. AB - BACKGROUND: Coaching psychology is of increasing interest to medical educators for its potential benefits as a facilitative method in problem-based learning (PBL). However, the field lacks empirical studies that explore the lived experiences of students and tutors in the PBL coaching process. This study aimed to elicit knowledge regarding medical students' and tutors' experiences and perceptions of PBL coaching in the context of Chinese undergraduate medical education. METHODS: The qualitative methodology of interpretative phenomenological analysis (IPA) was employed. Participants comprised third year medical students (n=20) and PBL tutors (n=5) who have adopted a coaching approach in PBL for a semester. Semi-structured interviews were utilized to obtain a comprehensive understanding of their experiences of PBL coaching. Data analysis followed an iterative four-stage scheme of Biggerstaff and Thompson. RESULTS: Six main themes emerged from diverse experiences and interpretations: 1) mindsets of coaching and learning, 2) the development of learning dispositions and capacities, 3) student group collaboration, 4) tutor-student relationships, 5) personal and professional development, and 6) challenges and difficulties in implementation. CONCLUSIONS: It could be concluded that PBL coaching is a dynamic, facilitative process that makes a particular contribution to the learning process from psychological, emotional, and social perspectives, whilst it demonstrates significant overlaps with PBL tutoring in terms of supporting students' cognitive activities in PBL. Further research is needed to identify the barriers and challenges for medical educators to implement coaching in the PBL process. PMID- 27396901 TI - Differential Effects of Neighborhood Type on Adolescent Alcohol Use in New Zealand. AB - Identifying neighborhood typologies associated with adolescent alcohol use can inform the development of harm reduction strategies. Utilizing data from a nationally representative youth survey (n = 4267) in New Zealand, latent class analysis was used to categorize neighborhood types (defined by 10 demographic, social and environmental indicators) to investigate their association with alcohol consumption and related harm. Three neighborhood types were distinguished: (1) "high outlet density and economic deprivation" (30 % of all neighborhoods); (2) "high deprivation, social disorganization, and unsafe" (38 %); and (3) "higher income, safe, and socially organized" (32 %). Significant ethnic variation was evident between neighborhood types. There was an age-group interaction in the main effects with significant associations between neighborhood type and drinking measures and harm most apparent among younger adolescents (<16 years), as described next. Compared to students residing in "higher income, safe, and socially organized" neighborhoods, the frequency of binge drinking and high typical consumption was significantly higher in students residing in "high outlet density and economic deprivation" and "high deprivation, social disorganization, and unsafe", with students residing in "high outlet density and economic deprivation" also experiencing higher levels of alcohol related harm. The findings that neighborhoods characterized by high deprivation and alcohol outlet density and low social organization and perceptions of safety were associated with risky drinking patterns and harm, specifically among young adolescents, underscores the importance of adopting a developmental approach to the study of contextual effects on adolescents. PMID- 27396902 TI - [Postoperative external beam radiotherapy for medullary thyroid carcinoma with high risk of locoregional relapse]. AB - PURPOSE: To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. PATIENTS AND METHODS: Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. RESULTS: Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. CONCLUSION: Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse. PMID- 27396903 TI - Feasibility evaluation of prone breast irradiation with the Sagittilt(c) system including residual-intrafractional error assessment. AB - PURPOSE: Feasibility evaluation of the Sagittilt(c) prone breast board system (Orfit Industries, Wijnegem, Belgium) for radiotherapy focusing on patient and staff satisfaction, treatment time, treatment reproducibility with the assessment of residual-intrafractional errors. MATERIAL AND METHODS: Thirty-six patients underwent whole-breast irradiation in prone position. Seventeen received a sequential boost (breast: 42.56Gy in 16 fractions, boost: 10Gy in five fractions), while 19 patients received a concomitant boost protocol (breast/boost: 45.57/55.86Gy in 21 fractions). Treatment verification included a daily online cone-beam CT (CBCT). In order to assess the residual and residual intrafractional errors post-treatment CBCTs were performed systematically at the first five treatment sessions. Treatment time, patient comfort, staff satisfaction were also evaluated. RESULTS: The pretreatment CBCT resulted in a population systematic error of 4.5/3.9/3.3mm in lateral/longitudinal/vertical directions, while the random error was 5.4/3.8/2.8mm. Without correction these would correspond to a clinical to planning target volume margin of 15.0/12.3/10.3mm. The population systematic and random residual-intrafractional errors were 1.5/0.9/1.7mm and 1.7/1.9/1.6mm. Patient and staffs' satisfaction were considered good and average. The mean treatment session time was 21minutes (range: 13-40min). CONCLUSION: The Sagittilt(c) system seems to be feasible for breast irradiation and well-tolerated by patients, acceptable to radiographers and reasonable in terms of treatment times. Set-up accuracy was comparable with other prone systems; residual errors need further investigations. PMID- 27396904 TI - Effect of O6-Substituted Guanine Analogs on O6-methylguanine DNA methyltransferase Expression and Glioblastoma Cells Viability. AB - BACKGROUND: Glioblastoma multiforme (GBM) is often associated with a poor survival prognostic for patients. The main reason seems to be the acquired or inherent resistance to the chemotherapeutic agent used to treat the tumor, temozolomide (TMZ). To this day, the most recognized pathway of resistance is the DNA Direct Repair pathway by the means of the protein O6- methylguanine DNA methyltransferase (MGMT). OBJECTIVES: To design and synthesize a series of MGMT inhibitors that can sensitize GBM cells to TMZ. METHODS: Twenty-five O6-alkyl, O6 aryl and O6-substituted-aryl guanine analogs including nine novel compounds were synthesized, characterized, analyzed by molecular docking and tested on the T98G GBM cells viability. RESULTS: Following molecular modeling with MGMT, the newly designed compounds 19, 22, and 24 emerged as the most promising MGMT ligands and displayed modest cytotoxicity. Guanine analog (19), bearing a p-nitrobenzyl moiety, reduced considerably the O6-methylguanine DNAmethyltransferase expression level. When combined with TMZ (1), which is used as first line treatment for brain tumors, compounds 19, 22, and 24 decreased T98G cells proliferation by 32%, 68% and 50%, respectively. TMZ (1) displayed negligible effect on the proliferation of these cells further supporting the notion that this cell model is resistant to this alkylating agent. CONCLUSION: Overall, these results notably highlight a group of MGMT inhibitors that warrants further exploration in the development of therapeutic options to circumvent TMZ resistance in brain tumors. PMID- 27396905 TI - A fatal case of paramethoxyamphetamine poisoning and its detection in hair. AB - Paramethoxyamphetamine (PMA) is a phenethylamine derivative that is structurally related to 3,4-methylenedioxymethamphetamine (MDMA), but has higher toxicity than MDMA. Here, we report a fatal intoxication case involving PMA. A 36-year-old man was found dead in a hotel room. Toxicological analysis revealed that PMA concentrations were 0.57 and 0.59mg/L in peripheral and heart blood, respectively. Ketamine and diazepam were also detected in his blood. Based on toxicological results and autopsy findings, the cause of death was determined to be acute fatal intoxication with PMA. Hair analysis using gas chromatography/mass spectrometry was performed and PMA was detected at a concentration of 20.1ng/mg after methanol extraction for 20h. This is the first report of the determination of PMA concentration in the hair from a drug abuser. PMID- 27396906 TI - Acid-Mediated N-H/alpha,beta-C(sp(3))-H Trifunctionalization of Pyrrolidine: Intermolecular [3 + 2] Cycloaddition for the Construction of 2,3-Dihydro-1H Pyrrolizine Derivatives. AB - A one-pot acid-mediated reaction has been developed for the N-H/alpha,beta C(sp(3))-H trifunctionalization of pyrrolidine without any metallic reagents or external oxidants. This reaction involves the intermolecular [3 + 2] cycloaddition of in situ-generated azomethine ylides with acrylic esters to provide facile access to 2,3-dihydro-1H-pyrrolizine derivatives in high yields under mild conditions. PMID- 27396907 TI - Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease. AB - We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial. PMID- 27396908 TI - Peripheral injection of bombesin induces c-Fos in NUCB2/nesfatin-1 neurons. AB - As anorexigenic hormones bombesin and nucleobindin2 (NUCB2)/nesfatin-1 decrease food intake in rodents. Both hormones have been described in brain nuclei that play a role in the modulation of hunger and satiety, like the paraventricular nucleus of the hypothalamus (PVN) and the nucleus of the solitary tract (NTS). However, the direct interaction of the two hormones is unknown so far. The aim of study was to elucidate whether bombesin directly interacts with NUCB2/nesfatin-1 neurons in the PVN and NTS. Therefore, we injected bombesin intraperitoneally (ip) at two doses (26 and 32nmol/kg body weight) and assessed c-Fos activation in the PVN, arcuate nucleus (ARC) and NTS compared to vehicle treated rats (0.15M NaCl). We also performed co-localization studies with oxytocin or tyrosine hydroxylase. Bombesin at both doses increased the number of c-Fos positive neurons in the PVN (p<0.05) and NTS (p<0.05) compared to vehicle, while in the ARC no modulation was observed (p>0.05). In the PVN and NTS the number of c-Fos positive neurons colocalized with NUCB2/nesfatin-1 increased after bombesin injection compared to vehicle treatment (p<0.05). Moreover, an increase of activated NUCB2/nesfatin-1 immunoreactive neurons that co-expressed oxytocin in the PVN (p<0.05) or tyrosine hydroxylase in the NTS (p<0.05) was observed compared to vehicle. Our results show that peripherally injected bombesin activates NUCB2/nesfatin-1 neurons in the PVN and NTS giving rise to a possible interaction between bombesin and NUCB2/nesfatin-1 in the modulation of food intake. PMID- 27396909 TI - Electroacupuncture inhibits pruritogen-induced spinal microglial activation in mice. AB - In this study, we examined whether electroacupuncture (EA) represses pruritogen induced microglial activation. Immunohistochemical studies revealed that a subcutaneous (s.c.) injection of the pruritogen 5'-guanidinonaltrindole (GNTI; 0.3mg/kg) to the back of the neck in mice induced acute expression of the ionized calcium-binding adaptor molecule 1 (Iba1) in both gray and white matter of the spinal cord, with the highest expression in the dorsal horn area. EA application (2Hz) to LI4 and LI11 attenuated GNTI-induced scratching behavior and repressed GNTI-induced Iba1 expression and Iba1 (+) microglia in the dorsal horn. In contrast, EA at the ST36 acupoint had no such effects. Confocal image analysis revealed co-expression of phosphorylated p38 and Iba1 in microglia with EA at the ST36 acupoint, but not at the LI4 or LI11 acupoints. In Western blot analysis, s.c. injection of GNTI to the back of the neck increased Iba1 and phospho-p38 expression in the spinal cord as compared with injection of saline, while EA at LI4 and LI11 reduced GNTI-induced expression of Iba1 and phospho-p38. These findings indicate that EA at LI4 and LI11, but not at ST36, reduces GNTI-induced microglial activation in the mouse spinal cord. PMID- 27396910 TI - The Faulty Perinatal Hormonal Imprinting as Functional Teratogen. AB - Perinatally, the developmental window for the adjustment of hormone receptors to their target hormones is open. The hormonal imprinting which determines the relationship of hormones and receptors for life takes place in this period. The recognition ability of developing receptors is not yet entirely specific, so they could be 'cheated' by false imprinters such as related hormones, drugs, environmental pollutants or certain food components and faulty imprinting may result. This causes a functional developmental abnormality, which is then manifested, at any later time in life, as the alteration of the binding capacity of hormone receptors. With or without the presence of other factors this could cause problems in hormone regulated functions or may result in diseases. So it may be stated that faulty hormonal imprinting, caused by a broad spectrum of receptor level molecules, is acting as a functional teratogen. This means that functional maldevelopment is not restricted to intrauterine life, but can also occur after birth, in the perinatal period. The inclusion of faulty imprinting as maldevelopment widens both the list of functional teratogens and the period of teratogenicity. The importance and danger of faulty imprinting is high, especially considering its heritable (transgenerational) character. Considering the facts, the attitudes in the present-day perinatal treatments and medical training must be changed. PMID- 27396911 TI - Hierarchical nanostructure and synergy of multimolecular signalling complexes. AB - Signalling complexes are dynamic, multimolecular structures and sites for intracellular signal transduction. Although they play a crucial role in cellular activation, current research techniques fail to resolve their structure in intact cells. Here we present a multicolour, photoactivated localization microscopy approach for imaging multiple types of single molecules in fixed and live cells and statistical tools to determine the nanoscale organization, topology and synergy of molecular interactions in signalling complexes downstream of the T cell antigen receptor. We observe that signalling complexes nucleated at the key adapter LAT show a hierarchical topology. The critical enzymes PLCgamma1 and VAV1 localize to the centre of LAT-based complexes, and the adapter SLP-76 and actin molecules localize to the periphery. Conditional second-order statistics reveal a hierarchical network of synergic interactions between these molecules. Our results extend our understanding of the nanostructure of signalling complexes and are relevant to studying a wide range of multimolecular complexes. PMID- 27396912 TI - Methylation of LOXL1 Promoter by DNMT3A in Aged Human Skin Fibroblasts. AB - Lysyl oxidase-like 1 (LOXL1) is an amino-oxidase involved in maturation of elastic fibers. Its downregulation has been associated with elastic fibers repair loss in aging aorta, lung, ligament, and skin. Several evidences of LOXL1 epigenetic silencing by promoter methylation were reported in cancer and cutis laxa syndrome. We hypothesized that this mechanism could be implicated in skin aging process, as far as elastic fibers are also concerned. Anti-DNMT3A chromatin immunoprecipitation was conducted with nuclear extracts from skin fibroblasts isolated from young and elderly individuals, and showed a higher level of DNMT3A protein binding to the LOXL1 promoter in older cells concomitantly to the decrease of LOXL1 mRNA expression and the increase of LOXL1 promoter methylation. Using luciferase reporter assay driven by LOXL1 promoter in HEK293 cells, we demonstrated that LOXL1 transcriptional activity was dramatically reduced when a recombinant DNMT3A was concomitantly overexpressed. LOXL1 promoter transcriptional activity was restored in the presence of a broad-spectrum inhibitor of DNMT activity, 5-aza-2'-deoxycytidine. Finally, to assess whether the interplay between DNMT3A and LOXL1 promoter could be targeted to increase LOXL1 mRNA expression level, an Origanum majorana extract was selected among 43 plant extracts as a new inhibitor of human DNMT3A activity to restore LOXL1 secretion without cytotoxicity in aged skin fibroblasts. PMID- 27396913 TI - Brief Intervention to Make Teachers More Empathic Leads to Fewer Student Suspensions. PMID- 27396914 TI - The Impact of Media Use on Sleep in Adolescents. PMID- 27396915 TI - Structure-Activity Relationship Studies on Holy Basil (Ocimum sanctum L.) Based Flavonoid Orientin and its Analogue for Cytotoxic Activity in Liver Cancer Cell Line HepG2. AB - O. sanctum L. (O. tenuiflorum) is an important sacred medicinal plant of India known as Holy Basil or Tulsi. The chemical composition of volatile oil is highly complex and comprises high ratio of phenylpropanoids and terpenes, and some phenolic compound or flavonoids such as orientin and vicenin. These minor flavonoids are known to be antioxidant and anticancer in nature. Orientin reported as potential anticancer agent due to anti-proliferative activity on human liver cancer cell line HepG2, but its mechanism of action is not fully explored. In the present work an in-silico structure-activity relationship study on orientin was performed and built a pharmacophore mapping and QSAR model to screen out the potential structurally similar analogues from chemical database of Discovery Studio (DSv3.5, Accelrys, USA) as potential anticancer agent. Analogue fenofibryl glucuronide was selected for in vitro cytotoxic/anticancer activity evaluation through MTT assay. Binding affinity and mode of action of orientin and its analogue were explored through molecular docking studies on quinone oxidoreductase, a potential target of flavonoids. Contrary to the assumption, in vitro results showed only 41% cell death at 202.389 MUM concentration (at 96 hrs). Therefore, we concluded that the selected orientin analogue fenofibryl glucuronide was non-cytotoxic/non-anti-carcinogenic up to 100 MUg/ml (202.389 MUM) concentrations for a long term exposure i.e., till 96 hrs in human cancer cells of HepG2. We concluded that orientin and its analogue fenofibryl glucuronide as pure compound showed no activity or less cytotoxicity activity on liver cancer cell line HepG2. PMID- 27396916 TI - Regioselctive Thiocyanation of Aromatic and Heteroaromatic Compounds Using a Novel Bronsted Acidic Ionic Liquid. AB - A convenient procedure for the preparation of 1-(1-Propylsulfonic)-3- methylimidazolium thiocyanate as a novel Bronsted acidic ionic liquid thiocyanation agent and highly efficient heterogeneous catalytic is described. This catalyst is used in regioselective thiocyanation of indoles, anilines, pyrroles and their derivatives (aromatic and heteroaromatic organic compounds) in the presence of H2O2 as a mild and oxidant in EtOH:H2O (1:1 v/v). These reactions are performed under mild and simple conditions and give regioselective products in high yields and short reaction time. PMID- 27396917 TI - Triple-drug therapy to prevent pancreatic fistula after pancreatectomy in a rat model. AB - BACKGROUND: Pancreatic fistula (PF) is one of post-operative complications in pancreatic surgery, but there is no consensus about the optimal treatment for PF. Our group has established a rat model of PF, and we conducted the present investigation to determine the efficacy of the triple-drug therapy (somatostatin analogue, gabexate mesilate, and imipenem/cilastatin) against PF using our rat model. METHODS: In the PF rat model, the triple-drug therapy was administered to the treated (T) group (n = 4), and we compared the results with those of a control (C) group (n = 4). The rats were sacrificed on postoperative day 3 (POD 3) and the levels of amylase and lipase in serum and ascites were measured. The intra-abdominal adhesion was scored. Each pancreas was evaluated pathologically, and inflammation was scored. RESULTS: The ascitic amylase levels on POD 3 were 1982 (1738-2249) IU/L in the C group and significantly lower at 136 (101-198) IU/L in the T group (p = 0.02). The ascitic lipase levels on POD 3 were 406 (265 478) U/L in the C group and significantly lower at 13 (7-17) U/L in the T group (p = 0.02). The intra-abdominal adhesion score on POD 3 was 2 (1-2) in the C group and significantly lower at 0 (0-1) in the T group (p = 0.02). The histological evaluation showed that the average of pancreatic inflammatory score was 8.5 (8-9) in the C group and significantly milder at 5 (5-7) in the T group (p = 0.01). CONCLUSION: Our findings suggest that the triple-drug therapy could be useful as a treatment for PF in clinical settings. PMID- 27396918 TI - Capillary electrophoresis method to determine siRNA complexation with cationic liposomes. AB - Small interfering RNA (siRNA) inducing gene silencing has great potential to treat many human diseases. To ensure effective siRNA delivery, it must be complexed with an appropriate vector, generally nanoparticles. The nanoparticulate complex requires an optimal physiochemical characterization and the complexation efficiency has to be precisely determined. The methods usually used to measure complexation in gel electrophoresis and RiboGreen(r) fluorescence based assay. However, those approaches are not automated and present some drawbacks such as the low throughput and the use of carcinogenic reagents. The aim of this study is to develop a new simple and fast method to accurately quantify the complexation efficiency. In this study, capillary electrophoresis (CE) was used to determine the siRNA complexation with cationic liposomes. The short-end injection mode applied enabled siRNA detection in less than 5 min. Moreover, the CE technique offers many advantages compared with the other classical methods. It is automated, does not require sample preparation and expensive reagents. Moreover, no mutagenic risk is associated with the CE approach since no carcinogenic product is used. Finally, this methodology can also be extended for the characterization of other types of nanoparticles encapsulating siRNA, such as cationic polymeric nanoparticles. PMID- 27396919 TI - Natural Products Combating Neurodegeneration: Parkinson's Disease. AB - Parkinson's disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents. PMID- 27396920 TI - Metallic and semiconducting carbon nanotubes separation using an aqueous two phase separation technique: a review. AB - It is known that carbon nanotubes show desirable physical and chemical properties with a wide array of potential applications. Nonetheless, their potential has been hampered by the difficulties in acquiring high purity, chiral-specific tubes. Considerable advancement has been made in terms of the purification of carbon nanotubes, for instance chemical oxidation, physical separation, and myriad combinations of physical and chemical methods. The aqueous two-phase separation technique has recently been demonstrated to be able to sort carbon nanotubes based on their chirality. The technique requires low cost polymers and salt, and is able to sort the tubes based on their diameter as well as metallicity. In this review, we aim to provide a review that could stimulate innovative thought on the progress of a carbon nanotubes sorting method using the aqueous two-phase separation method, and present possible future work and an outlook that could enhance the methodology. PMID- 27396921 TI - Incontinentia Pigmenti Coxsackium. AB - Late recurrences of first-stage inflammatory vesiculobullous lesions of incontinentia pigmenti (IP) are uncommon but have been reported to occur in the setting of infections, fevers, and vaccinations. This phenomenon has not been described in the setting of atypical hand, foot, and mouth disease (HFMD). In addition, atypical HFMD often has a predilection for areas of previous inflammation or trauma, such as areas of atopic dermatitis (eczema coxsackium). We present a case of incontinentia pigmenti coxsackium in which a coxsackievirus infection triggered reactivation of IP and cutaneous viral lesions were concentrated in areas of IP. PMID- 27396923 TI - Electrocardiographic Responses to Deer Hunting in Men and Women. AB - OBJECTIVE: Deer hunting includes various stimuli resulting in augmented sympathetic activity, increased heart rate (HR) response, and rhythm changes. Collectively, these superimposed stresses may increase an individual's risk for cardiovascular events. We undertook this study to evaluate HR and rhythm responses in multiple phases of deer hunting in men and women with and without cardiovascular disease (CVD). METHODS: Nineteen participants age 38.3 +/- 13.8 years (mean +/- SD) with body mass index 29.2 +/- 6.9 kg/m(2) followed their normal hunting routine. HR and rhythm were recorded continuously during the hunt using a small leadless electrocardiogram (ECG) patch monitor. RESULTS: Data were collected on 13 of 19 hunters while hiking. Three hunters recorded HR >=85% of their age-predicted heart rate maximum (HRmax) for 1 to 2 minutes. Arrhythmias were detected in both participants with CVD and in 8 without CVD. Recorded rhythms included premature atrial, junctional, and ventricular complexes. Six hunters climbed a tree stand; 3 of them recorded HR >=85% HRmax with sustained elevated HR response for 2 to 3 minutes with premature junctional contractions. Four of 19 participants dragged deer carcasses. During the drag, 1 male hunter recorded an HR of 91% HRmax, and another male hunter without CVD recorded an exercise-induced ischemic ECG. Fifteen of 19 hunters experienced "buck fever" (acute extreme excitation), with 7 reaching >=85% HRmax for up to 1 minute. Ventricular bigeminy and trigeminy and ventricular couplets were observed in 1 subject during buck fever. CONCLUSIONS: Men and women with and without CVD recorded substantial increases in HR and clinically relevant arrhythmias while deer hunting. PMID- 27396922 TI - Electrochemical Characterization of a Novel Exoelectrogenic Bacterium Strain SCS5, Isolated from a Mediator-Less Microbial Fuel Cell and Phylogenetically Related to Aeromonas jandaei. AB - A facultative anaerobic bacterium, designated as strain SCS5, was isolated from the anodic biofilm of a mediator-less microbial fuel cell using acetate as the electron donor and alpha-FeOOH as the electron acceptor. The isolate was Gram negative, motile, and shaped as short rods (0.9-1.3 MUm in length and 0.4-0.5 MUm in width). A phylogenetic analysis of the 16S rRNA, gyrB, and rpoD genes suggested that strain SCS5 belonged to the Aeromonas genus in the Aeromonadaceae family and exhibited the highest 16S rRNA gene sequence similarity (99.45%) with Aeromonas jandaei ATCC 49568. However, phenotypic, cellular fatty acid profile, and DNA G+C content analyses revealed that there were some distinctions between strain SCS5 and the type strain A. jandaei ATCC 49568. The optimum growth temperature, pH, and NaCl (%) for strain SCS5 were 35 degrees C, 7.0, and 0.5% respectively. The DNA G+C content of strain SCS5 was 59.18%. The isolate SCS5 was capable of reducing insoluble iron oxide (alpha-FeOOH) and transferring electrons to extracellular material (the carbon electrode). The electrochemical activity of strain SCS5 was corroborated by cyclic voltammetry and a Raman spectroscopic analysis. The cyclic voltammogram of strain SCS5 revealed two pairs of oxidation reduction peaks under anaerobic and aerobic conditions. In contrast, no redox pair was observed for A. jandaei ATCC 49568. Thus, isolated strain SCS5 is a novel exoelectrogenic bacterium phylogenetically related to A. jandaei, but shows distinct electrochemical activity from its close relative A. jandaei ATCC 49568. PMID- 27396924 TI - Pathophysiologic Determination of Frostbite Under High Altitude Environment Simulation in Sprague-Dawley Rats. AB - OBJECTIVES: Pathophysiologic changes of frostbite have been postulated but rarely understood, especially the changes caused by chilly high altitude environment. Therefore, we investigated the pathophysiologic changes of high altitude frostbite (HAF) caused by cold and hypoxia. METHODS: Forty Sprague-Dawley rats were randomly divided into 5 equal groups, namely, control, superficial HAF (S HAF), partial-thickness HAF (PT-HAF), full-thickness HAF (FT-HAF), and partial thickness normal frostbite (PT-NF) groups. The S-HAF, PT-HAF, and FT-HAF groups were fed under hypobaric hypoxic conditions simulating an altitude of 5000 m. Then, the PT-NF, S-HAF, PT-HAF, and FT-HAF models were constructed by controlling the duration of the direct freezing by liquid nitrogen. Animal vital signs were measured after the operation, and histopathologic changes were observed after routine hematoxylin and eosin staining. In addition, the microcirculation of frostbite tissues was monitored and compared by contrast ultrasonography during wound healing. RESULTS: The S-HAF, PT-HAF, and FT-HAF groups showed significant differences in the microcirculatory and histopathologic changes in the various tissue layers (P < .05). In addition, combined cold and hypoxia caused more damage to frostbite tissue than pure cold. The circulation recovery of HAF models was significantly slower relative to NF models (P < .05). CONCLUSIONS: A safe and reproducible HAF model was proposed. More important, pathophysiologic determination of HAF provided the foundation and potential for developing novel and effective frostbite therapies. PMID- 27396925 TI - Epidemiology of Feature-Specific Injuries Sustained by Skiers in a Snow Park. AB - OBJECTIVE: The objective of the present case series study was to analyze injury types and injured anatomic locations resulting from skiing in snow park (SP) features and to determine potential risk factors for ski injuries in an SP. METHODS: The study was conducted during the 2013-2014 winter season in the SP of a major winter resort located in the Spanish Pyrenees. Cases involved skiers who experienced feature-related injuries in the SP. A total of 113 cases met the inclusion criteria. Logistic regression was used to calculate the odds of injury types and injury to anatomic locations on aerial versus nonaerial features. RESULTS: The overall injury rate was 0.9 per 1000 skier runs. The proportion of injuries was higher for aerials (1.18% of uses) than for nonaerials (0.66% of uses). Results revealed that the upper extremities were the most commonly injured body region, and sprains/strains/dislocations and fractures were the most common injury type. CONCLUSIONS: The most commonly injured anatomic location on nonaerial features was the face, while on aerial features it was the head. A higher proportion of fractures was observed on aerial features, while a higher proportion of sprains/strains/dislocations was observed on nonaerial features. Prevention strategies to reduce injury risk include SP redesign, safety and communication policies, instruction on technical skills, and promotion of the use of protective equipment. PMID- 27396926 TI - Dendriform Pulmonary Ossification in a Subclinical Case of Familial Pulmonary Fibrosis. PMID- 27396928 TI - Detection of l-alanylaminopeptidase activity in microorganisms using fluorogenic self-immolative enzyme substrates. AB - A series of fluorogenic enzymatic substrates that incorporate a self-immolative spacer were synthesised for the purpose of identifying l-alanylaminopeptidase activity in microorganisms in agar media. These substrates resulted in the generation of fluorescent microorganism colonies with Gram-negative microorganisms. PMID- 27396927 TI - Chemoenzymatic synthesis and antileukemic activity of novel C9- and C14 functionalized parthenolide analogs. AB - Parthenolide is a naturally occurring terpene with promising anticancer properties, particularly in the context of acute myeloid leukemia (AML). Optimization of this natural product has been challenged by limited opportunities for the late-stage functionalization of this molecule without affecting the pharmacologically important alpha-methylene-gamma-lactone moiety. Here, we report the further development and application of a chemoenzymatic strategy to afford a series of new analogs of parthenolide functionalized at the aliphatic positions C9 and C14. Several of these compounds were determined to be able to kill leukemia cells and patient-derived primary AML specimens with improved activity compared to parthenolide, exhibiting LC50 values in the low micromolar range. These studies demonstrate that different O-H functionalization chemistries can be applied to elaborate the parthenolide scaffold and that modifications at the C9 or C14 position can effectively enhance the antileukemic properties of this natural product. The C9-functionalized analogs 22a and 25b were identified as the most interesting compounds in terms of antileukemic potency and selectivity toward AML versus healthy blood cells. PMID- 27396929 TI - Synthesis and biological evaluation of Oblongifolin C derivatives as c-Met inhibitors. AB - Oblongifolin C, one of the polyprenylated benzoylphloroglucinol natural products (PPAPs) isolated from the fruits of Garcinia yunnanensis Hu, was recently discovered to be a potent anti-tumor agent. A collection of 12 derivatives with modifications on the benzophenone moieties were synthesized and tested for c-Met kinase inhibition and cytotoxicity against the HepG2, Miapaca-2, HCC827, Hela, A549, AGS, and HT-29 cell lines in vitro. An oxidized derivative, 10, was found to possess strong inhibition and anti-migration properties in the HCC827 cell line and serves as a potential lead compound for the development of new anticancer drugs. In addition, structure-activity relationships (SAR) were also evaluated to provide key information for future anticancer drug development. PMID- 27396931 TI - Corrigendum. PMID- 27396930 TI - Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties. AB - Condensation of substituted anthranilic acids with 4-isothiocyanatoethyl benzenesulfonamide led to series of heterocyclic benzenesulfonamides incorporating 2-mercapto-quinazolin-4-one tails. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA XII (a transmembrane, tumor-associated enzyme also involved in glaucoma-genesis). The new sulfonamides acted as medium potency inhibitors of hCA I (KIs of 28.5-2954nM), being highly effective as hCA II (KIs in the range of 0.62-12.4nM) and XII (KIs of 0.54 7.11nM) inhibitors. All substitution patterns present in these compounds (e.g., halogens, methyl and methoxy moieties, in positions 6, 7 and/or 8 of the 2 mercapto-quinazolin-4-one ring) led to highly effective hCA II/XII inhibitors. These compounds should thus be of interest as preclinical candidates in pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and XII as targets) or some tumors in which the activity of isoforms CA II and XII is dysregulated. PMID- 27396932 TI - Predictive models in cancer management: A guide for clinicians. AB - BACKGROUND: Predictive tools in cancer management are used to predict different outcomes including survival probability or risk of recurrence. The uptake of these tools by clinicians involved in cancer management has not been as common as other clinical tools, which may be due to the complexity of some of these tools or a lack of understanding of how they can aid decision-making in particular clinical situations. AIMS: The aim of this article is to improve clinicians' knowledge and understanding of predictive tools used in cancer management, including how they are built, how they can be applied to medical practice, and what their limitations may be. METHODS: Literature review was conducted to investigate the role of predictive tools in cancer management. RESULTS: All predictive models share similar characteristics, but depending on the type of the tool its ability to predict an outcome will differ. Each type has its own pros and cons, and its generalisability will depend on the cohort used to build the tool. These factors will affect the clinician's decision whether to apply the model to their cohort or not. CONCLUSIONS: Before a model is used in clinical practice, it is important to appreciate how the model is constructed, what its use may add over and above traditional decision-making tools, and what problems or limitations may be associated with it. Understanding all the above is an important step for any clinician who wants to decide whether or not use predictive tools in their practice. PMID- 27396933 TI - Proliferative index facilitates distinction between benign biliary lesions and intrahepatic cholangiocarcinoma. AB - Differentiation between benign and malignant lesions of the hepatic biliary tree may pose a diagnostic problem because well-differentiated intrahepatic cholangiocarcinoma may mimic biliary hamartoma, bile duct adenoma, or parenchymal extinction. We evaluated Ki-67 proliferative index and p53 status by immunohistochemical staining to aid in exclusion of cholangiocarcinoma. Fourteen biliary hamartomas, 21 bile duct adenomas, and 11 livers with parenchymal extinction were compared with 26 intrahepatic cholangiocarcinomas (16 well differentiated and 10 moderately or poorly differentiated tumors). We found an increased proliferative index in intrahepatic cholangiocarcinomas compared with benign biliary lesions (average 23.0% in cholangiocarcinoma versus 1.4% in all benign biliary lesions, n = 26 versus n = 46, P < .001). No difference in average proliferative index was observed between well-differentiated and moderately/poorly differentiated cholangiocarcinomas (average 22.7% versus 23.3%, n = 16 versus n = 10, P = .92). Average proliferation indices of benign biliary lesions were uniformly low (biliary hamartoma, 1.2%; bile duct adenoma, 2%; parenchymal extinction, 0.5%). Most cholangiocarcinomas (23/26; 88.5%), but none of the benign lesions (0/46; 0%), had proliferative indices greater than 10%. Strong nuclear p53 immunohistochemical staining was only seen in cholangiocarcinomas (9/26; 34.6%) and not in benign biliary lesions (0/46; 0%), although many of the benign lesions showed weak to moderate staining. Immunohistochemical staining for Ki-67 facilitates distinction between benign and malignant lesions of the intrahepatic biliary tree, whereas p53 immunohistochemical staining is less helpful. PMID- 27396934 TI - Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma. AB - Kidney transplant recipients are at increased risk for malignancy, with about 5% incidence of cancer in native end-stage kidneys. Carcinoma in the renal allograft is far less common. Prior studies have demonstrated a propensity for renal cell carcinomas (RCCs) of papillary subtypes in end-stage kidneys, and perhaps in allograft kidneys, but most allograft studies lack detailed pathologic review and predate the current classification system. We reviewed our experience with renal carcinoma in kidney allografts at 2 academic centers applying the International Society of Urological Pathology classification, informed by immunohistochemistry. The incidence of renal allograft carcinoma was about 0.26% in our population. Of 12 allograft carcinomas, 6 were papillary (50%), 4 were clear cell (33%), 1 was clear cell (tubulo)papillary, and 1 chromophobe. Two of the papillary carcinomas had distinctive biphasic glomeruloid architecture matching the newly named "biphasic squamoid alveolar" pattern and were difficult to classify on core biopsies. The 2 cell types had different immunophenotypes in our hands (eosinophilic cells: RCC-/CK34betaE12+ weight keratin +/cyclin D1+; clear cells: RCC+/cytokeratin high molecular weight negative to weak/cyclin D1-). None of the patients experienced cancer recurrences or metastasis. Our study confirms the predilection for papillary RCCs in kidney allografts and highlights the occurrence of rare morphologic variants. Larger studies are needed with careful pathologic review, which has been lacking in the literature. PMID- 27396935 TI - Long-term effects of joint bleeding before starting prophylaxis in severe haemophilia. AB - INTRODUCTION: Early initiation of prophylaxis in severe haemophilia is critical for effective prevention of arthropathy. However, the optimum time for starting prophylaxis has not been established yet. AIM: This study assessed long-term effects of age at starting prophylaxis and joint bleeding before prophylaxis on haemophilic arthropathy. METHODS: In patients with severe haemophilia (FVIII/IX <0.01 IU mL-1 ), born between 1965 and 2000, haemophilic arthropathy was evaluated on X-rays. Patient groups were compared by multivariable regression analysis, adjusted for bleeding phenotype and lifetime intensity of prophylaxis. RESULTS: One hundred and twenty-four patients were evaluated at a median age of 22 years. When comparing patients according to age at starting prophylaxis, starting before age 6 years was significantly better than starting later (P < 0.01), but no additional benefit of starting before age 3 years was demonstrated. The number of joint bleeds before prophylaxis had a stronger association with arthropathy than age at starting prophylaxis. Starting prophylaxis before the onset of joint bleeding resulted in the best long-term outcome (P <= 0.02); starting after one joint bleed appeared to have acceptable long-term outcome. The difference between starting after 0-1 and 2-5 joint bleeds was notable, but statistical significance was not reached (P = 0.15). CONCLUSION: Future research with more patients on early prophylaxis will have to clarify whether starting prophylaxis before joint bleeding is superior. PMID- 27396936 TI - Intratracheal therapy with autologous bone marrow-derived mononuclear cells reduces airway inflammation in horses with recurrent airway obstruction. AB - This research evaluated the effects of bone marrow-derived mononuclear cells (BMMCs) on the inflammatory process in the equine recurrent airway obstruction (RAO). Eight horses in RAO clinical score were divided into cell therapy group (Gcel) treated with a single intratracheal dose of BMMCs, and dexamethasone group (Gdex) treated with 21days of oral dexamethasone. The horses were clinically revaluated on days 7 and 21, together with cytological evaluation of the BALF, and detection of inflammatory markers (interleukins [IL]-10, -4, and -17, and interferon gamma and alpha). There were decreases in respiratory effort and clinical score on days 7 and 21(p<0.05) for both groups. The percentage of neutrophils decreased and macrophages increased on days 7 and 21 (p<0.005) in both groups. IL-10 levels increased in the Gcel group on day 21 compared to days 0 and 7 (p<0.05), but this was not observed in the Gdex group. The quantification of IL-4, IL-17, IFN-gamma, and IFN-alpha did not change between evaluations in both groups. These preliminary results suggest that BMMCs may ameliorate the inflammatory response of RAO. PMID- 27396938 TI - Bioethanol production by reusable Saccharomyces cerevisiae immobilized in a macroporous monolithic hydrogel matrices. AB - Performance of yeasts on industrial processes can be dramatically improved by immobilization of the biocatalyst. The immobilization of Saccharomyces cerevisiae inside monolithic macroporous hydrogels were produced by in-situ polymerization of acrylamide around a live yeast suspension under cryogelation conditions. Preculture of the yeasts was not necessary and this innovative and simple procedure is amenable to scaling-up to industrial production. The yeasts were efficiently retained in monolithic hydrogels, presenting excellent mechanical properties and high cell viability. Macroporous hydrogels showed a fast mass transport allowing the hydrogel-yeast complexes achieved similar ethanol yield and productivity than free yeasts, which is larger than those reached with yeasts immobilized in compact hydrogels. Moreover, the same yeasts were able to maintain its activity by up to five reaction cycles with a cell single batch during fermentation reactions. PMID- 27396937 TI - Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects. AB - Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2A-eGFP transgene using zinc finger nucleases (ZFNs) to generate corrected WAS-iPSC (cWAS-iPSC). WASp and GFP were first expressed in the earliest CD34(+)CD43(+)CD45(-) hematopoietic precursor cells and later in all hematopoietic lineages examined. Whereas differentiation to non-lymphoid lineages was readily obtained from WAS iPSCs, in vitro T lymphopoiesis from WAS-iPSC was deficient with few CD4(+)CD8(+) double-positive and mature CD3(+) T cells obtained. T cell differentiation was restored for cWAS-iPSCs. Similarly, defects in natural killer cell differentiation and function were restored on targeted correction of the WAS locus. These results demonstrate that the defects exhibited by WAS-iPSC-derived lymphoid cells were fully corrected and suggests the potential therapeutic use of gene-corrected WAS-iPSCs. PMID- 27396939 TI - Process development for oxidations of hydrophobic compounds applying cytochrome P450 monooxygenases in-vitro. AB - Cytochrome P450 monooxygenases are a unique family of enzymes that are able to catalyze regio- and stereospecific oxidations for a broad substrate range. However, due to limited enzyme activities and stabilities, hydrophobicity of substrates, as well as the necessity of a continuous electron and oxygen supply the implementation of P450s for industrial processes remains challenging. Aim of this study was to point out key aspects for the development of an efficient synthesis concept for cytochrome P450 catalyzed oxidations. In order to regenerate the natural cofactor NADPH, a glucose dehydrogenase was applied. The low water soluble terpene alpha-ionone was used as substrate for the model reaction system. The studies reveal that an addition of surfactants in combination with low volumetric amounts of co-solvent can significantly increase substrate availability and reaction rates. Furthermore, these additives facilitated a reliable sampling procedure during the process. Another key factor for the process design was the oxygen supply. Based on various investigations, a bubble-aerated stirred tank reactor in batch mode represents a promising reactor concept for P450 oxidations. Main restriction of the investigated reaction system was the low process stability of the P450 monooxygenase, characterized by maximum total turnover numbers of ~4100molalpha-ionone/molP450. PMID- 27396940 TI - Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem. AB - Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC) based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of >= 0.5 and < 1cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2cm(3) to 21.9cm(3). Regarding the dose homogeneity index (HIICRU) and conformity index (CIICRU) were without significant difference between techniques statistically. However, the average CIICRU = 1.09 +/- 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 +/- 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V4Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V2Gy of normal brain, VMAT plans had attained 6.4 +/- 5%; this was significantly better (p < 0.05) than either DCA or IMRS plans, at 9.2 +/- 7% and 8.2 +/- 6%, respectively. Owing to the multiple arc or beam planning designs of IMRS and VMAT, both of these techniques required higher MU delivery than DCA, with the averages being twice as high (p < 0.05). If linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem. PMID- 27396941 TI - Urethral dose sparing in squamous cell carcinoma of anal canal using proton therapy matching electrons with prior brachytherapy for prostate cancer: A case study. AB - The purpose of this case study is to communicate a technique on treating the re irradiation of squamous cell carcinoma (SCC) of anal canal with proton fields matched with electron fields to spare prostatic urethra. A 76-year old male presented with a secondary radiation-induced malignancy as a result of prostate brachytherapy seeds irradiation 10 years prior. A rectal examination revealed a bulky tumor at the top of the anal canal involving the left superior-most aspect of the anal canal extending superiorly into the rectum. The inferior extent was palpable approximately 3cm from the anal verge and the superior extent of the mass measured greater than 5cm in the superior-inferior dimension. Chemoradiation was suggested since the patient was opposed to abdominoperineal resection (APR) and colostomy. The use of proton therapy matching with electron fields in the re irradiation setting could help reduce the complications. A 2 lateral proton beams were designed to treat the bulky tumor volume with 2 electron beams treating the nodal volumes. This complication of treatment fields helped spare the prostatic urethra and reduced the risk of urinary obstruction in the future. PMID- 27396942 TI - Adjacent Lichen Sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma. AB - OBJECTIVE: In this study, we investigated if the presence of histologically abnormal epithelium adjacent to the primary tumour influenced the frequency, timing, and topography of local vulvar recurrences (LVR) following treatment for squamous cell carcinoma of the vulva (VSCC). METHODS: The study population comprised a cohort of 201 consecutive cases with incident VSCC. LVR were categorised as local relapses (LR) if they occurred <2cm from the tumour margins, and as second field tumours (SFT) when >=2cm from these margins. Univariable and multivariable competing risk modelling was performed to identify the prognostic factors associated with local disease recurrence. RESULTS: The characterization of the epithelium adjacent to the invasive component was possible for 199 (99.0%) patients. Of these, 171 (85.9%) were found to have intraepithelial abnormalities found adjacent to the surgical specimen. Multivariable analyses revealed that, following adjustment, Lichen Sclerosis (LS) was associated with an increase in the incidence of LVR, LR and SFT (SHRs: 3.4, 2.7 and 4.4, respectively). Although the incidence of LR and SFT in women with LS associated VSCC was similar, the peak incidence of SFT occurred more than two years before that of LR. CONCLUSIONS: Women with VSCC arising in a field of LS may continue to have an increased risk of developing LR and SFT for many years after resection of their primary tumour. Our study suggests that these women should be followed up more regularly so that LVR can be detected earlier; unless a more robust surveillance programme or chemopreventative treatments become available. PMID- 27396943 TI - Results of less radical fertility-sparing procedures with omitted parametrectomy for cervical cancer: 5years of experience. AB - OBJECTIVE: The aim of our study was to describe oncological and obstetrical outcomes in patients who underwent less radical fertility-sparing surgical (FSS) procedures with omitted parametrectomy for cervical cancer. METHODS: Included were women with cervical cancer stages IA2-IB2 who were under the age of 40 and desired future pregnancy. Patients underwent pelvic lymphadenectomy and sentinel lymph node biopsy. Node-negative cases underwent subsequent cervical surgery and were further analyzed. Neoadjuvant chemotherapy (NAC) was administered in patients with tumors >2cm and/or involving >2/3 of cervical stroma. Simple vaginal trachelectomy or needle conization were performed according to tumor extent and topography. The follow-up period started once free surgical margins were reached. RESULTS: Out of 44 women enrolled, 32 women (IA2=7, IB1=23, IB2=2) successfully completed FSS. NAC was administered in 9 (28.1%) cases. A simple trachelectomy was performed in 11 patients and needle conization in 21 patients. During the follow-up, 6 out of 32 women became pregnant. Of these, 1 miscarried and 5 successfully delivered. Disease recurred in 6 patients; 5 recurrences were central and 1 recurrence presented as an ovarian mass. Invasive cervical carcinoma, high-grade squamous intraepithelial (HSIL), and low-grade squamous intraepithelial (LSIL) lesions were detected in 4, 1 and 1 patients, respectively. Three of them received NAC. All events were detected within 16months after surgery. CONCLUSIONS: Nearly 27% of patients cannot complete FSS due to node positivity, progression during NAC, or involved margins. The total recurrence rate reached 18.8%, with the majority of invasive recurrences detected in patients after NAC followed by FSS. These patients represent cases at a higher risk of recurrence even if adequate free margins are reached by surgery. Nearly half of the cohort did not consider pregnancy in the near future because of personal reasons. PMID- 27396944 TI - CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors. AB - Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. PMID- 27396945 TI - Isocapnic hyperventilation shortens washout time for sevoflurane - an experimental in vivo study. AB - BACKGROUND: Isocapnic hyperventilation (IHV) is a method that fastens weaning from inhalation anaesthesia by increasing airway concentration of carbon dioxide (CO2 ) during hyperventilation (HV). In an animal model, we evaluated a technique of adding CO2 directly to the breathing circuit of a standard anaesthesia apparatus. METHODS: Eight anaesthetised pigs weighing 28 +/- 2 kg were intubated and mechanically ventilated. From a baseline ventilation of 5 l/min, HV was achieved by doubling minute volume and fresh gas flow. Respiratory rate was increased from 15 to 22/min. The CO2 absorber was disconnected and CO2 was delivered (DCO2 ) to the inspiratory limb of a standard breathing circuit via a mixing box. Time required to decrease end-tidal sevoflurane concentration from 2.7% to 0.2% was defined as washout time. Respiration and haemodynamics were monitored by blood gas analysis, spirometry, electric impedance tomography and pulse contour analysis. RESULTS: A DCO2 of 261 +/- 19 ml/min was necessary to achieve isocapnia during HV. The corresponding FICO2 -level remained stable at 3.1 +/- 0.3%. During IHV, washout of sevoflurane was three times faster, 433 +/- 135 s vs. 1387 +/- 204 s (P < 0.001). Arterial CO2 tension and end-tidal CO2 , was 5.2 +/- 0.4 kPa and 5.6 +/- 0.4%, respectively, before IHV and 5.1 +/- 0.3 kPa and 5.7 +/- 0.3%, respectively, during IHV. CONCLUSIONS: In this experimental in vivo model of isocapnic hyperventilation, the washout time of sevoflurane anaesthesia was one-third compared to normal ventilation. The method for isocapnic hyperventilation described can potentially be transferred to a clinical setting with the intention to decrease emergence time from inhalation anaesthesia. PMID- 27396946 TI - Peroxynitrite-mediated oxidation of plasma fibronectin. AB - Fibronectin is a large dimeric glycoprotein present in both human plasma and in basement membranes. The latter are specialized extracellular matrices underlying endothelial cells in the artery wall. Peroxynitrous acid (ONOOH) a potent oxidizing and nitrating agent, is formed in vivo from superoxide and nitric oxide radicals by stimulated macrophages and other cells. Considerable evidence supports ONOOH involvement in human atherosclerotic lesion development and rupture, possibly via extracellular matrix damage. Here we demonstrate that Tyr and Trp residues on human plasma fibronectin are highly sensitive to ONOOH with this resulting in the formation of 3-nitrotyrosine, 6-nitrotryptophan and dityrosine as well as protein aggregation and fragmentation. This occurs with equimolar or greater levels of oxidant, and in a dose-dependent manner. Modification of Tyr was quantitatively more significant than Trp (9.1% versus 1.5% conversion with 500MUM ONOOH) after accounting for parent amino acid abundance, but only accounts for a small percentage of the total oxidant added. LC-MS studies identified 28 nitration sites (24 Tyr, 4 Trp) with many of these present within domains critical to protein function, including the cell-binding and anastellin domains. Human coronary artery endothelial cells showed decreased adherence and cell-spreading on ONOOH-modified fibronectin compared to control, consistent with cellular dysfunction induced by the modified matrix. Studies on human atherosclerotic lesions have provided evidence for co-localization of 3 nitrotyrosine and fibronectin. ONOOH-mediated fibronectin modification and compromised cell-matrix interactions, may contribute to endothelial cell dysfunction, a weakening of the fibrous cap of atherosclerotic lesions, and an increased propensity to rupture. PMID- 27396947 TI - Additional pitfalls of using 1,1-ADEQUATE for structure elucidation. AB - 1,1-ADEQUATE is a powerful and robust NMR experiment to establish carbon-carbon connectivities using modest sample quantities when cryogenic probe technology is available. Yet potential pitfalls of applying this method are not widely appreciated, such as weak or missing 1 JCC correlations in strongly coupled 13 C 13 C AB spin systems and unusually large multi-bond (n JCC ) correlations associated with particular functional groups. These large n JCC correlations observed in 1,1-ADEQUATE spectra could be mistaken for 1 JCC correlations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27396948 TI - Combination treatment with extended-infusion ceftazidime/avibactam for a KPC-3 producing Klebsiella pneumoniae bacteraemia in a kidney and pancreas transplant patient. PMID- 27396949 TI - Cell wall glycopolymers of Firmicutes and their role as nonprotein adhesins. AB - Cell wall glycopolymers (CWGs) of gram-positive bacteria have gained increasing interest with respect to their role in colonization and infection. In most gram positive pathogens they constitute a large fraction of the cell wall biomass and represent major cell envelope determinants. Depending on their chemical structure they modulate interaction with complement factors and play roles in immune evasion or serve as nonprotein adhesins that mediate, especially under dynamic conditions, attachment to different host cell types. In particular, covalently peptidoglycan-attached CWGs that extend well above the cell wall seem to interact with glyco-receptors on host cell surfaces. For example, in the case of Staphylococcus aureus, the cell wall-attached teichoic acid (WTA) has been identified as a major CWG adhesin. A recent report indicates that a type-F scavenger receptor, termed SR-F1 (SREC-I), is the predominant WTA receptor in the nasal cavity and that WTA-SREC-I interaction plays an important role in S. aureus nasal colonization. Therefore, understanding the role of CWGs in complex processes that mediate colonization and infection will allow novel insights into the mechanisms of host-microbiota interaction. PMID- 27396950 TI - In solution SERS sensing using mesoporous silica-coated gold nanorods. AB - Mesoporous silica-coated gold nanorods (AuNR@MS) act as a colloidally stable Raman sensing platform with a built-in analyte size cutoff. Herein, these core shell plasmonic nanostructures were presented with a range of thiolated Raman active molecules to probe the limits of this platform for SERS sensing. The experimental results show generally, that the transport of molecules through the mesopores is highly dependent on the size of the molecule and specifically, that AuNR@MS with pores of ~4 nm diameter are able to sense analytes with molecular dimensions smaller than 1.5 nm. This sensing platform will likely find broad use, performing well even in complex media based on the high colloidal stability imbued by the mesoporous silica shell. PMID- 27396951 TI - A validated microRNA profile with predictive potential in glioblastoma patients treated with bevacizumab. AB - PURPOSE: We investigated whether microRNA expression data from glioblastoma could be used to produce a profile that defines a bevacizumab responsive group of patients. PATIENTS AND METHODS: TCGA microRNA expression data from tumors resected at first diagnosis of glioblastoma in patients treated with bevacizumab at any time during the course of their disease were randomly separated into training (n = 50) and test (n = 37) groups for model generation. MicroRNA-seq data for 51 patients whose treatment included bevacizumab in the BELOB trial were used as an independent validation cohort. RESULTS: Using penalized regression we identified 8 microRNAs as potential predictors of overall survival in the training set. We dichotomized the response score based on the most prognostic minimum of a density plot of the response scores (log-rank HR = 0.16, p = 1.2e( 5)) and validated the profile in the test cohort (one-sided log-rank HR = 0.34, p = 0.026). Analysis of the profile using all samples in the TCGA glioblastoma dataset, regardless of treatment received, (n = 473) showed that the prediction of patient benefit was not significant (HR = 0.84, p = 0.083) suggesting the profile is specific to bevacizumab. Further independent validation of our microRNA profile in RNA-seq data from patients treated with bevacizumab (alone or in combination with CCNU) at glioblastoma recurrence in the BELOB trial confirmed that our microRNA profile predicted patient benefit from bevacizumab (HR = 0.59, p = 0.043). CONCLUSION: We have identified and validated an 8-microRNA profile that predicts overall survival in patients with glioblastoma treated with bevacizumab. This may be useful for identifying patients who are likely to benefit from this agent. PMID- 27396953 TI - Closing the gap in Genetic Data Analysis pipelines with ASPIREdb. PMID- 27396954 TI - Skewed X-inactivation and Females with Intellectual Disability. PMID- 27396952 TI - SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism. AB - It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA-sequencing demonstrated that the snoRNA host gene 16 (SNHG16) is significantly up-regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt-regulated transcription factors, including ASCL2, ETS2, and c-Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16 indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved in lipid metabolism was also observed in clinical tumors. Argonaute CrossLinking and ImmunoPrecipitation (AGO CLIP) demonstrated that SNHG16 heavily binds AGO and has 27 AGO/miRNA target sites along its length, indicating that SNHG16 may act as a competing endogenous RNA (ceRNA) "sponging" miRNAs off their cognate targets. Most interestingly, half of the miRNA families with high confidence targets on SNHG16 also target the 3'UTR of Stearoyl-CoA Desaturase (SCD). SCD is involved in lipid metabolism and is down-regulated upon SNHG16 silencing. In conclusion, up-regulation of SNHG16 is a frequent event in CRC, likely caused by deregulated Wnt signaling. In vitro analyses demonstrate that SNHG16 may play an oncogenic role in CRC and that it affects genes involved in lipid metabolism, possible through ceRNA related mechanisms. PMID- 27396955 TI - Identification of 83 Novel Alpha-Mannosidosis-Associated Sequence Variants: Functional Analysis of MAN2B1 Missense Mutations. PMID- 27396956 TI - Levetiracetam for Pediatric Posttraumatic Seizure Prophylaxis. AB - Investigators from Nationwide Children's Hospital performed an observational cohort study of early post-traumatic seizures (EPTS) among 34 children with moderate to severe traumatic brain injury (TBI) who received levetiracetam (LEV) prophylaxis following admission to their pediatric intensive care unit. PMID- 27396957 TI - Under-reported data analysis with INAR-hidden Markov chains. AB - In this work, we deal with correlated under-reported data through INAR(1)-hidden Markov chain models. These models are very flexible and can be identified through its autocorrelation function, which has a very simple form. A naive method of parameter estimation is proposed, jointly with the maximum likelihood method based on a revised version of the forward algorithm. The most-probable unobserved time series is reconstructed by means of the Viterbi algorithm. Several examples of application in the field of public health are discussed illustrating the utility of the models. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27396961 TI - Coming in postgraduate medicine. PMID- 27396958 TI - Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells. AB - Durable antibody production after vaccination or infection is mediated by long lived plasma cells (LLPCs). Pathways that specifically allow LLPCs to persist remain unknown. Through bioenergetic profiling, we found that human and mouse LLPCs could robustly engage pyruvate-dependent respiration, whereas their short lived counterparts could not. LLPCs took up more glucose than did short-lived plasma cells (SLPCs) in vivo, and this glucose was essential for the generation of pyruvate. Glucose was primarily used to glycosylate antibodies, but glycolysis could be promoted by stimuli such as low ATP levels and the resultant pyruvate used for respiration by LLPCs. Deletion of Mpc2, which encodes an essential component of the mitochondrial pyruvate carrier, led to a progressive loss of LLPCs and of vaccine-specific antibodies in vivo. Thus, glucose uptake and mitochondrial pyruvate import prevent bioenergetic crises and allow LLPCs to persist. Immunizations that maximize these plasma cell metabolic properties might thus provide enduring antibody-mediated immunity. PMID- 27396960 TI - Concurrent Myelomatous Pleural Effusion and Extramedullary Mediastinal Involvement as an Initial Manifestation of Multiple Myeloma. AB - BACKGROUND Myelomatous pleural effusion (MPE) is a rare occurrence in patients with multiple myeloma (MM). Fewer than 20 cases of MPE have been reported as an initial manifestation of MM. Extramedullary plasmacytoma (EMP) occurs in fewer than 5% patients with MM, and mediastinal EMP is even rarer, with only about 80 cases reported in the literature. We present a case study involving a patient with concurrent MPE and mediastinal EMP as an initial manifestation of MM. CASE REPORT The patient was a 74-year-old nonsmoking female with a 3-month history of exertional dyspnea and back pain. On exam, the patient was afebrile (temperature 37.2 degrees C), blood pressure was 160/74 mm Hg, heart rate was 92 bpm, respiratory rate was 22/min, and oxygen saturation was 87% on room air. Patient was in mild distress and had decreased breath sounds over right lung fields about halfway up with dullness to percussion. Computed tomography of the chest showed a moderate-sized right pleural effusion and an anterior mediastinal mass. Thoracentesis showed a lymphocyte-predominant exudate. Cytology showed numerous plasma cells including immature forms. Stains for CD138 were positive, confirming plasma cell origin of cells. The anterior mediastinal mass was also biopsied and showed diffuse infiltrate of lymphocytes with plasma cell features that were also positive for CD138. Systemic protein electrophoresis showed a monoclonal immunoglobulin G kappa spike, and bone marrow biopsy was consistent with MM. CONCLUSIONS MPE and EMP are extremely rare manifestations in MM. In addition, it is extremely rare for these to be the presenting features of MM. We report concurrently occurring MPE and EMP in a patient as her initial manifestation of MM. PMID- 27396962 TI - Problem solutions. PMID- 27396959 TI - RIPK1 and RIPK3 Kinases Promote Cell-Death-Independent Inflammation by Toll-like Receptor 4. AB - Macrophages are a crucial component of the innate immune system in sensing pathogens and promoting local and systemic inflammation. RIPK1 and RIPK3 are homologous kinases, previously linked to activation of necroptotic death. In this study, we have described roles for these kinases as master regulators of pro inflammatory gene expression induced by lipopolysaccharide, independent of their well-documented cell death functions. In primary macrophages, this regulation was elicited in the absence of caspase-8 activity, required the adaptor molecule TRIF, and proceeded in a cell autonomous manner. RIPK1 and RIPK3 kinases promoted sustained activation of Erk, cFos, and NF-kappaB, which were required for inflammatory changes. Utilizing genetic and pharmacologic tools, we showed that RIPK1 and RIPK3 account for acute inflammatory responses induced by lipopolysaccharide in vivo; notably, this regulation did not require exogenous manipulation of caspases. These findings identified a new pharmacologically accessible pathway that may be relevant to inflammatory pathologies. PMID- 27396963 TI - Editor's mail. PMID- 27396964 TI - Prospectus A rated guide to CME courses. PMID- 27396965 TI - Problems solutions. PMID- 27396966 TI - Research reports. PMID- 27396967 TI - Washington background. PMID- 27396968 TI - John p. connors 1928-1975. PMID- 27396969 TI - Introducing a core curriculum offering cme credit. PMID- 27396970 TI - Readysource MANAGING DIABETES. PMID- 27396971 TI - Cme credit quiz. PMID- 27396973 TI - Boosting catalyst activity in cis-selective semi-reduction of internal alkynes by tailoring the assembly of all-metal aromatic tri-palladium complexes. AB - Highly symmetric [Pd3]+ clusters that present delocalized metal-metal bonds can catalyse the selective semi-reduction of internal alkynes to cis-alkenes. Studies on factors governing the formation of all-metal aromatics enabled the design of an optimised catalytic system that delivers cis-alkenes with almost complete selectivity on a gram scale with very low catalyst loadings (0.03 mol%). PMID- 27396974 TI - Effect of nurse staffing variation and hospital resource utilization. AB - In this study, we examined the effect of variations in nurse staffing levels on the length of stay and medical expenses of patients who underwent hip or knee surgeries. A cross-sectional study was conducted using the National Health Insurance database and hospital surveys from 2010. Patient length of stay and medical expenses by nurse staffing level and skill mix were compared after adjusting for hospital and patient characteristics. Nurse staffing was measured based on staffing grade, the bed-to-registered nurse/nurse aid ratio, the bed-to nursing personnel ratio, and the RN proportion. Generalized estimation models were used to analyze the associations. Decreased nurse staffing was consistently associated with increased length of stay, regardless of nurse staffing measures. The medical expenses associated with the lowest staffing level were approximately $US 1142.2 more than those associated with the highest staffing level. The study results suggest that maintaining a high nurse staffing level could be a cost effective strategy for government and insurers, as well as for patients. We propose that policy makers implement more efficient nurse staffing strategies. PMID- 27396975 TI - Management of pregnancies complicated by hypertensive disorders of pregnancy: Could we do better? AB - BACKGROUND: Hypertensive disorders are among the most common medical problems in pregnancy. Compliance with clinical practice guidelines has potential to translate to significant maternal and perinatal health benefits. AIMS: To evaluate compliance with Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) clinical guidelines for management of hypertension during pregnancy. METHODS: Inclusion criteria: women with hypertension in pregnancy who gave birth at a tertiary obstetric centre in 2010. Compliance with SOMANZ guidelines was assessed, as well as uptake of findings from the 'Induction of labour versus expectant monitoring for mild gestational hypertension/pre eclampsia after 36 weeks' gestation' (HYPITAT) trial. RESULTS: Of 5624 women, 516 (9.2%) were identified with hypertension (49 chronic hypertension (CH); 457 gestational hypertension (GH) or pre-eclampsia (PE)). Thresholds to diagnose hypertension and initiate anti-hypertensive treatment were consistent with SOMANZ recommendations. Among women with CH, only 12.2% were prescribed aspirin prior to 16 weeks as PE prophylaxis. Of women with PE, 37 (18.6%) had known risk factors for development of PE at the initial visit yet only nine (24.3%) received aspirin. Of the 244 women who met HYPITAT inclusion criteria at 36 weeks, 174 (77.7%) were managed expectantly; nine (5.2%) developed severe adverse outcomes. CONCLUSION: Current management guidelines for hypertension treatment were generally followed, although aspirin prophylaxis was frequently overlooked, resulting in up to 19 excess PE cases. Uptake of recommendations from the HYPITAT trial was low; however, severe complications were fewer than expected. Overall, this suggests that clinicians appropriately weigh up the likely maternal risk compared to infant benefits of deferred delivery in each case, a key recommendation of HYPITAT-II. PMID- 27396976 TI - Errors in meta-analyses of selection. PMID- 27396977 TI - P-glycoprotein overexpression in bone marrow-derived multipotent stromal cells decreases the risk of steroid-induced osteonecrosis in the femoral head. AB - P-glycoprotein (P-gp) plays a role in steroid-induced osteonecrosis of the femoral head (ONFH), but the underlying mechanism remains unknown. We hypothesized that P-gp overexpression can prevent ONFH by regulating bone marrow derived multipotent stromal cell (BMSC) adipogenesis and osteogenesis. BMSCs from Sprague-Dawley rats were transfected with green fluorescent protein (GFP) or the multidrug resistance gene 1 (MDR1) encoding GFP and P-gp. Dexamethasone was used to induce BMSC differentiation. Adipogenesis was determined by measuring peroxisome proliferator-activated receptor (PPAR-gamma) expression and the triglyceride level. Osteogenesis was determined by measuring runt-related transcription factor 2 (Runx2) expression and alkaline phosphatase activity. For in vivo experiments, rats were injected with saline, BMSCs expressing GFP (GFP BMSCs) or BMSCs expressing GFP-P-gp (MDR1-GFP-BMSCs). After dexamethasone induction, adipogenesis was determined by measuring PPAR-gamma expression and fatty marrow, whereas osteogenesis was detected by measuring Runx2 expression, trabecular parameters and the mineral apposition rate, followed by evaluation of the incidence of ONFH. Overexpression of P-gp in BMSCs resulted in markedly decreased expression of adipogenic markers and increased expression of osteogenic markers. Compared with rats injected with saline, rats injected with GFP-BMSCs showed reduced ONFH, and the injected GFP-positive BMSCs attached to trabecular surfaces and exhibited an osteoblast-like morphology. Compared with the rats injected with BMSCs expressing GFP alone, rats injected with BMSCs overexpressing GFP and P-gp showed lower adipocytic variables, higher osteogenic variables and lower incidence of ONFH. Overexpression of P-gp inhibited BMSC adipogenesis and promoted osteogenesis, which reduced the incidence of steroid-induced ONFH. PMID- 27396978 TI - An Alignment-Free "Metapeptide" Strategy for Metaproteomic Characterization of Microbiome Samples Using Shotgun Metagenomic Sequencing. AB - In principle, tandem mass spectrometry can be used to detect and quantify the peptides present in a microbiome sample, enabling functional and taxonomic insight into microbiome metabolic activity. However, the phylogenetic diversity constituting a particular microbiome is often unknown, and many of the organisms present may not have assembled genomes. In ocean microbiome samples, with particularly diverse and uncultured bacterial communities, it is difficult to construct protein databases that contain the bulk of the peptides in the sample without losing detection sensitivity due to the overwhelming number of candidate peptides for each tandem mass spectrum. We describe a method for deriving "metapeptides" (short amino acid sequences that may be represented in multiple organisms) from shotgun metagenomic sequencing of microbiome samples. In two ocean microbiome samples, we constructed site-specific metapeptide databases to detect more than one and a half times as many peptides as by searching against predicted genes from an assembled metagenome and roughly three times as many peptides as by searching against the NCBI environmental proteome database. The increased peptide yield has the potential to enrich the taxonomic and functional characterization of sample metaproteomes. PMID- 27396979 TI - Respiratory depression detected by capnography among children in the postanesthesia care unit: a cross-sectional study. AB - BACKGROUND: Children are at risk for respiratory depression while recovering from anesthesia. Currently, monitoring children in the postanesthesia care unit (PACU) with pulse oximetry is recommended. However, pulse oximetry does not reliably recognize hypoventilation or apnea, particularly in the presence of supplemental oxygen. Capnography is a sensitive monitor of ventilation that is not often used in the PACU. AIM: To determine the frequency of hypoventilation and apnea as detected by capnography among children in the PACU. METHODS: In a cross-sectional study, capnography monitoring was applied to healthy children of age 1-17 years in the PACU of a tertiary care hospital. Staff was blinded to the capnography monitor; alarms were disabled. Staff provided routine care and monitoring with pulse oximetry to all patients. Vital signs, patient interventions, and medication administration were recorded by a research assistant every 30 s until all monitoring was discontinued by staff. Outcome measures included frequency of hypoventilation and apnea as measured by capnography and oxygen desaturations as measured by pulse oximetry, as well as staff interventions for these events. RESULTS: Data from 194 children were analyzed. Capnography detected hypoventilation or apnea in 45.5% (95% CI 38.5%, 52.5%) of patients. Oxygen desaturations occurred in 19% (95% CI 13%, 24%) of patients. Interventions occurred in 9% (95% CI 5%, 13%) of patients. Patients who received narcotic medications were more likely to experience hypoventilation (OR 2.3, 95% CI 1.02, 5.3) and apnea (OR 2.7, 95% CI 1.1, 7). Hypoventilation was seen more often among children who received supplemental oxygen (OR 3.1, 95% CI 1.1, 12). CONCLUSIONS: Hypoventilation and apnea are common among children in the PACU; however, few interventions occur to address these events. Routine monitoring with capnography may improve recognition of respiratory depression and enhance patient safety in the PACU. PMID- 27396981 TI - Raiders of the lost mark - endothelial cells and their role in transplantation for hematologic malignancies. AB - Endothelial cells (EC) are crucial for normal angiogenesis and important for patients with leukemia, myeloma, and lymphoma during and after hematopoietic stem cell transplantation (HSCT). Knowledge of endothelial dysfunction in hematologic malignancies is provided by translational studies analyzing soluble endothelial markers, morphologic and functional changes of EC cultured in patients' sera or enumeration of circulating EC or endothelial progenitor cells (EPC). EC are important for stem cell homing and maintenance. Endothelial activation or damage is a central component in the pathogenesis of several complications after HSCT, like acute and chronic graft-versus-host disease, sinusoidal obstruction syndrome, capillary leak syndrome, engraftment syndrome, diffuse alveolar syndrome, idiopathic pneumonia syndrome, and transplant-associated microangiopathy. Finally, EC or EPC may facilitate tumor cell survival thus representing potential factors for both disease progression and relapse in hematologic malignancies. PMID- 27396983 TI - Frontal cortex reactivity differentiates between schizophrenic subtypes: auditory ERP-evidence. AB - OBJECTIVES: To extend the hypothesis that late auditory EP shifts represent pathophysiologcial markers in schizophrenia. METHODS: Early negative (+/-100 MUs) and late positive (>300 ms) auditory oddball and CNV responses are topographically compared in 3 medicated schizophrenic subtypes. RESULTS: Only late cortical responses differentiate between paranoid, residual and disorganised schizophrenia. Core features of the deficit residual state encompass low-voltage N2P3 responses and missing central initial CNV components. Both paranoid and disorganised schizophrenics show a distinctive reactivity of the frontal cortex. Paranoid schizophrenia is characterized by an extensive frontal spread of the task-related P3 response. Disorganised schizophrenia shows a specifically increased frontal CNV component indicating a nonspecific arousal reaction. CONCLUSION: Combinations of late auditory EP-patterns fairly fit with the cognitive/behavioral status observed in schizophrenia spectrum disorders. PMID- 27396980 TI - Changes in cognitive function in women with HIV infection and early life stress. AB - INTRODUCTION: HIV is frequently associated with deficits in brain function, including memory, psychomotor speed, executive function and attention. Early life stress (ELS) has also been shown to have a direct influence on neurocognitive performance. However, little is known about the combined impact of ELS and HIV on neurocognitive function over time. The aim of the present study was to follow a cohort of affected women, allowing us to assess the effects of HIV and childhood trauma on cognition and the change in cognition over time. METHOD: A battery of neurocognitive tests was administered to 117 women at baseline and then a year later. The sample included a total of 67 HIV+ and 50 HIV- women, 71 with ELS and 46 without ELS. Controlling for age, education and antiretroviral therapy (ART) at baseline and 12-month follow-up, raw scores were compared across groups using a repeated-measures analysis of covariance. RESULTS: More women were on ART at follow-up compared to baseline. Results revealed a significant combined HIV and childhood trauma effect over time on the Wisconsin Card Sorting Test (p = .003) and Category Fluency Test (p = .006). A significant individual HIV effect over time was evident on the WAIS-III Digit Symbol Test (p = .03) and the Controlled Oral Word Association Test (p = .003). CONCLUSION: Findings suggest better performance in abstract reasoning, speed of information processing and verbal fluency over time. While all groups showed improvements that may correspond to practice effects, effects of HIV and childhood trauma remained evident at 12 month follow-up despite greater ART uptake and improved HIV disease status. This is the first study to assess the combined impact of HIV and trauma on neurocognitive function over time in an all-female cohort with more advanced disease. PMID- 27396984 TI - Psychobiological research on Dissociative Identity Disorder (DID): A methodological note. AB - BACKGROUND: To a large extent, discussions about dissociative identity disorder (DID) revolve around the way in which identity states (alters) that are thought to be typical for this condition should be interpreted: are they metaphors or are they genuine actors? Recent literature offers some fine examples of studies demonstrating that alters differ in their physiological profile. On the basis of this type of evidence, some authors have concluded that alters are more than just metaphors. OBJECTIVE: Drawing upon an experimental example, we argue that such a line of reasoning is highly problematic. METHOD & RESULTS: Our example demonstrates that normal subjects are perfectly able to simulate alters such that these alters are accompanied by different physiological profiles. This is especially true for subjects scoring high on fantasy proneness. CONCLUSIONS: Psychobiological research on DID should include normal controls, preferably controls who are fantasy prone. Unless such a strategy is adopted, psychobiological research on alter activity will not be very informative. PMID- 27396985 TI - Verminderde vergrijzing en M. Korsakov; toeval of een voorbeeld van serendiptisme? AB - The clinical observation that patients with an alcohol amnestic disorder get grey hair at a higher age was investigated by comparing a group of Korsakov patients and patients with alcohol abuse with a reference sample from the literature. Korsakoff patients appeared to be significantly less grey than age-matched alcoholics and controls. Some putative etiological factors including the mechanism of apoptosis are discussed. PMID- 27396986 TI - Een zeldzame oorzaak van dementie: de bestralingsencephalopathie. AB - We describe the clinical history of a 49-year old woman, who demonstrated progressive personality changes more than twenty years after radiation of a pituitary adenoma (prolactinoma), with apathy, loss of initiative, memory deficits, postural instability, dysarthria and faecal incontinence. Neuropsychological assessment showed impulsivity, loss of overview, desinhibition, fluctuating deficits of attention, and memory disturbances. MRI scanning of the brain revealed a cystic lesion along the right ventricle. The clinical picture and the findings of the other investigations are typical for dementia due to radiation encephalopathy. Such a long period between radiation and cognitive deterioration is rare, although it has been described before. PMID- 27396987 TI - Viability of Lucilia sericata maggots after exposure to wound antiseptics. AB - After debridement and before dressing a wound with maggots of calliphorid flies, one frequently performed step is the application of antiseptics to the prepared wound bed. However, the concomitant application of antiseptic agents during maggot therapy is regarded controversial as antiseptics may interfere with maggots' viability. In this experimental in vitro study, the viability of fly maggots was investigated after exposure to various antiseptics frequently used in wound care. Here, we show that Lucilia sericata fly maggots can survive up to an hour's exposure to wound antiseptics such as octenidine, povidone-iodine or polihexanide. Concomitant short-term application of wound antiseptics together with maggots on wound beds is tolerated by larvae and does not impair their viability. PMID- 27396988 TI - Farewell to life on land - thoracic strength as a new indicator to determine paleoecology in secondary aquatic mammals. AB - Habitat shifts from land to water have occurred independently in several mammal lineages. However, because we do not know completely about the relationship between skeletal morphology and function, both reliable life reconstructions of each extinct taxon and the timing of those shifts in locomotor strategies are yet to be fully understood. We estimated the strengths of rib cages against vertical compression in 26 extant and four extinct mammal specimens including cetartiodactyls, paenungulates, and carnivorans, representing 11 terrestrial, six semi-aquatic, and nine obligate aquatic taxa. Our analyses of extant taxa showed that strengths were high among terrestrial/semi-aquatic mammals, whose rib cages are subjected to vertical compression during the support on land, whereas strengths were low among obligate aquatic mammals, whose rib cages are not subjected to antigravity force in the water. We therefore propose rib strength as a new index to estimate the ability of an animal to be supported on land while being supported by either the forelimbs or thoracic region. According to our analyses of extinct taxa, this ability to be supported on land was rejected for a basal cetacean (Cetartiodactyla: Ambulocetus) and two desmostylians (Paenungulata: Paleoparadoxia and Neoparadoxia). However, this ability was not rejected for one desmostylian species (Desmostylus). Further study of the ribs of extant/extinct semi-aquatic taxa may help in understanding the ecological shifts in these groups. PMID- 27396989 TI - Prevalence and burden of dyspnoea among COPD patients in Japan. AB - BACKGROUND AND AIMS: Dyspnoea is the most common symptom of chronic obstructive pulmonary disease (COPD) significantly affecting activity, impairing patients' well-being and contributing to the economic burden of COPD. The objective of this study was to estimate the prevalence of dyspnoea and its impact on COPD management costs in Japan. METHODS: A cross-sectional survey was conducted among 82 internal medicine physicians and 85 respiratory specialists representing 420 patients with COPD in Japan. Information was collected on demographic and clinical characteristics, dyspnoea (mMRC scale), and healthcare resource use. Dyspnoea prevalence was estimated among all patients and those on specific COPD treatments. The economic burden was derived from two cohorts based on their level of dyspnoea that were matched by propensity scores balancing their demographic and disease burden characteristics. RESULTS: Moderate-severe dyspnoea (mMRC score >= 2) was reported by 37.5% of COPD patients and ranging from 21.5% among patients treated with a mono bronchodilator to 59.8% among patients treated with triple therapy. Descriptive analysis showed that dyspnoeic patients have higher annual costs attributable to consultations (?2999 vs. ?1906), medications (?1139 vs. ?716), exacerbations (?674 vs. ?36), other resources (?1789 vs. ?140) and in total (?6348 vs. ?2797) (p < 0.0001 for all comparisons) compared to patients with mild or no dyspnoea (mMRC score < 2). The total costs remained significantly higher in a propensity-matched cohort adjusted for severity and cardiovascular comorbidity [?6776.1 vs. ?4461.3, p = 0.0236]. CONCLUSION: Moderate-severe dyspnoea is common among consulting COPD patients in Japan and is a significant cost driver for the healthcare system. PMID- 27396990 TI - Mitigation of 3-Monochloro-1,2-propanediol Ester Formation by Radical Scavengers. AB - The present study investigated the possible mechanism of free radical scavengers on mitigation of 3-monochloro-1,2-propanediol (3-MCPD) fatty acid ester formation in vegetable oils. The electron spin resonance investigation showed that the concentration of free radicals could be clearly decreased in 1,2-distearoyl-sn glycerol (DSG) samples by all four antioxidants (l-ascorbyl palmitate, alpha tocopherol, lipophilic tea polyphenols, and rosemary extract) at 120 degrees C for 20 min under a N2 atmosphere. Moreover, the rosemary extract exhibited the highest inhibition efficiency. The Fourier transform infrared spectroscopy examination of DSG with alpha-tocopherol at 25 and 120 degrees C revealed that alpha-tocopherol could prevent the involvement of an ester carbonyl group of DSG in forming the cyclic acyloxonium free radical intermediate. Furthermore, the ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry analysis showed that alpha-tocopherol could suppress the formation of 3-MCPD di- and monoesters. Finally, the four antioxidants could decrease 3 MCPD esters in the palm oil during deodorization. Particularly, the rosemary extract also showed the highest efficiency in 3-MCPD ester mitigation. PMID- 27396991 TI - Recent advances in the synthesis of indolizines and their pi-expanded analogues. AB - Indolizine (pyrrolo[1,2-a]pyridine) is one of the five isomers of indole and it serves as a precursor for widespread indolizidine alkaloids. The straightforward synthesis of indolizines based on classical methodologies such as Scholtz or Chichibabin reactions has overshadowed numerous new strategies that have been revealed especially within the last ten years. The desire to achieve substitution patterns which were hard to build sparked the discovery of completely new pathways, e.g. transition metal-catalyzed reactions and approaches based on oxidative coupling. In this review, selected strategies toward indolizines published since 2005 are briefly summarized, commented upon, compared, and illustrated. The literature discussed here involves reactions based on either pyridine or pyrrole scaffolds, as well as selected methodologies leading to pi expanded indolizines. PMID- 27396993 TI - Rapid and Frequent Somatic Embryogenesis from Single Cells of Regenerated Carrot Plantlets. AB - Embryogenesis was induced from regenerated carrot plantlets in a shorter time and at a higher frequency than that observed previously from hypocotyl explants of carrot seedlings (Masuda et al. J. Plant Physiol. 145, 531 (1995)). Serial observations of embryogenesis from single cells to globular embryos via cell clusters were possible in the conditioned medium. The ability to produce embryos seemed to be acquired during the transition from torpedo-shaped embryos to regenerated plantlets, when differentiation of the epidermal cells of regenerated plantlets occurred. PMID- 27396992 TI - Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers. AB - Here we developed an integrated volumetric bar-chart chip (IV-Chip) technology by integration of our previous V-Chip with a fluid handling design to generate an instrument-free POC device and greatly reduce the detection time and effort. The IV-Chip test requires only 1 MUL of serum separated from finger-prick blood. The serum sample and ELISA reagents are directly loaded into the device using a pipette, and a shift of the two layers of the device generates homogeneous liquid segments in the microfluidic channel. Under vacuum pressure generated by a regular syringe, the segments flow into the ELISA wells in sequence and a sandwich ELISA reaction takes place. As a result of the automated washing and reacting strategy, the IV-Chip allows rapid tests for myocardial infarction biomarkers, and turnaround time is greatly reduced to 15 min. The specificity and accuracy of quantitative multiplex detection of MI biomarkers CK-MB, troponin I and myoglobin, are 87.5% and 95.8%, respectively. PMID- 27396994 TI - gamma-Glutamyl Transfer Reactions by Glutaminase from Pseudomonas nitroreducens IFO 12694 and Their Application for the Syntheses of Theanine and gamma Glutamylmethylamide. AB - In a mixture containing gamma-glutamyl donor (donor) and gamma-glutamyl acceptor (acceptor), the glutaminase of Pseudomonas nitroreducens IFO 12694 simultaneously catalyzed a gamma-glutamyl transfer reaction and hydrolysis of the donor. The variation of the activities responding to the concentration of glutathione and glycylglycine indicated that the enzyme might be classified in a group of glutaminases that shows hydrolysis prior to transfer reaction. On the other hand, the results with glutamine and ethylamine or methylamine indicated that the enzyme was active in the transfer reaction with suppressed hydrolysis of glutamine, and suggested the possibility of using the reaction for producing gamma-glutamylethylamide (theanine) or gamma-glutamylmethylamide (gamma-GMA). In fact, in a mixture containing high concentrations of substrates (0.7 M glutamine, 1.5 M ethylamine or methylamine) and 0.5 unit/ml glutaminase (borate buffer pH 11), 270 mM (47 g/L) theanine or 250 mM (38 g/L) gamma-GMA was formed in 7 h of incubation at 30 degrees C. PMID- 27396995 TI - Acetobacter xylinum Mutant with High Cellulose Productivity and an Ordered Structure. AB - Acetobacter xylinum subsp. sucrofermentans BPR2001, a cellulose-producing bacterium, that was newly isolated from a natural source, produced large amounts of the water-soluble polysaccharide, acetan. UDP-glucose is known to be the direct precursor in the synthetic pathways of both cellulose and acetan. We attempted to breed mutant strains and succeeded in obtaining one, BPR3001A, which produced 65% more bacterial cellulose and accumulated 83% less acetan than the parent strain, BPR2001. The cellulose formed was found to be structurally ordered, with higher degrees of polymerization and crystallinity and larger crystallite size than those produced by BPR2001 and other conventional strains. Furthermore, a processed dry sheet of this cellulose exhibited a higher Young's modulus than that of the wild strain. The ordered structure of the cellulose obtained was probably due to the decreased amount of acetan which may reflect the ribbon assembly of cellulose fibrils without prevention of hydrogen bonding between microfibrils. PMID- 27396996 TI - Oxidation Products of beta-Carotene during the Peroxidation of Methyl Linoleate in the Bulk Phase. AB - Methyl linoleate containing beta-carotene was autoxidized or photooxidized at 37 degrees C in the bulk phase, and the oxidation products of beta-carotene were analyzed by high-performance liquid chromatography. Formyl beta-carotenes, beta carotene 5,6-epoxide, and cyclic ethers of beta-carotene were detected as the oxidation products during the peroxidation of methyl linoleate initiated by a free radical initiator. These products, which were also detected in the methyl linoleate autoxidized without an initiator, were detectable only in much smaller amounts than the consumed beta-carotene. In the chlorophyll-sensitized photooxidation process, the products were beta-carotene 5,8-endoperoxide and beta carotene 5,6-epoxide. alpha-Tocopherol partially inhibited the formation of the 5,6-epoxide, but had no effect on the main product, the 5,8-endoperoxide. These results indicate that beta-carotene reacted with singlet oxygen to form the 5,8 endoperoxide as the primary product during the photooxidation of methyl linoleate, and that beta-carotene trapped lipid-peroxyl radicals to form oxygenated products which decomposed immediately during the autoxidation process. PMID- 27396997 TI - Characterization of the Immobilized beta-Galactosidase C from Bacillus circulans and the Production of beta(1->3)-linked Disaccharides. AB - A recombinant beta-galactosidase, which was obtained from the beta-galactosidase C gene of Bacillus circulans and cleaves the non-reducing end galactosyl residue of beta(1->3)-linkages selectively, was immobilized using CNBr-Sepharose. Although the effect of pH was not changed by the immobilization, the thermostability and stability in the presence of DMF were increased. Optimization of the transglycosylation using para-nitrophenyl beta-D-galactopyranoside as a donor and benzyl-alpha-D-N-acetylgalactosaminide as an acceptor afforded a beta(1 >3)-linked disaccharide derivative with 62% molar yield in a gram scale synthesis. Using the methyl-analogue as an acceptor, 53% of the acceptor was converted to the respective beta(1->3)-disaccharide. PMID- 27396998 TI - Three Different Types of alpha-Amylases from Aspergillus awamori KT-11: Their Purifications, Properties, and Specificities. AB - Three forms of alpha-amylases, designated Amyl I, Amyl II, and Amyl III were purified to a homogenous state by several column chromatographies from a koji culture in wheat bran of a strain of black mold, which was isolated in Indonesia and identified as Aspergillus awamori. They have molecular weights of 49,000, 63,000, and 97,000 by SDS-PAGE, respectively, and the optimum pHs were 4.0 for Amyl I and 5.5 for both Amyl II and Amyl III on soluble starch. Amyl I hydrolyzed malto-tetraose, -pentaose, -hexaose, -heptaose, and beta- and gamma-cyclodextrin to produce maltose and maltotriose as major products but not or hardly hydrolyzed maltose, isomaltose, maltotriose, isomaltotriose, alpha-cyclodextrin, or raw corn starch. On the other hand, both Amyl II and Amyl III hydrolyzed maltotriose as well as all the maltooligosaccharides described above and alpha-, beta-, and gamma-cyclodextrin, and even raw corn starch as well as heat-gelatinized corn starch to produce maltose as a major product and glucose and maltotriose as minor products, but they did not hydrolyze maltose, isomaltose, or isomaltotriose. The limit hydrolyses of soluble starch with three kinds of enzymes were 33% for Amyl I, 35% for Amyl II, and 38% for Amyl III, the reaction products had alpha anomeric forms by NMR analysis, and the blue color reaction with I2 disappeared completely at about 18% of hydrolysis of the starch for all enzymes. PMID- 27396999 TI - New Monoterpentriols from the Fruiting Body of Flammulina velutipes. AB - Two monoterpentriols were isolated from the stipe segment without either the pileus or apical growth zone of the harvested fruiting body of F. velutipes. The structures of these monoterpentriols were elucidated as (1R, 2R, 4R, 8S)-(-)-p menthane-2,8,9-triol (1) and its 8-epimer (2) based on a spectroscopic analysis and stereoselective chemical transformation from an authentic monoterpene alcohol. These monoterpentriols showed growth-promoting activities on the excised stipe with the pileus segment, which had been excised from a fruiting body just under the growth zone before the middle stage of the rapid growth period, at concentrations below 10 ppm, while the growth of the segment was inhibited at concentrations of 100 ppm and above. PMID- 27397000 TI - Breeding of a 5-Fluorouridine-resistant Mutant with Increased Cellulose Production from Acetobacter xylinum subsp. nonacetoxidans. AB - UDP-glucose (UDP-G), the direct precursor of cellulose, is known to be produced from UTP and glucose-1-phosphate. In an attempt to increase UTP biosynthesis, 5 fluorouridine (5-FUR: a pyrimidine analog)-resistant mutants were obtained using Acetobacter xylinum subsp. nonacetoxidans 757 as the parent strain. One of the 5 FUR-resistant mutants, FUR-35, showed about 40% higher cellulose productivion compared to the parent strain. Intracellular levels of UTP and UDP-G in FUR-35 was found to be higher than those in the parent strain. The carbamyl phosphate synthetase II (CPS) activity of FUR-35 was higher than that of the parent strain and the feedback inhibition of CPS by UTP in FUR-35 had been released compared with that in the parent strain. These results suggest that the increased cellulose production of FUR-35 was attributable to its higher of intracellular UDP-G level resulting from increased UTP biosynthesis. PMID- 27397001 TI - Possible Formation of Dehydro-L-ascorbic Acid from 2,3-Diketo-L-gulonic Acid in an Aqueous Solution. AB - The reaction of 2,3-diketo-L-gulonic acid (DKG), which is one of the important intermediate products in the degradation of L-ascorbic acid (ASA) in both food and biological systems, in an aqueous solution was studied. The formation of a small amount of the gamma-lactone, dehydro-L-ascorbic acid (DASA), from DKG was observed. This strongly suggests the chemical possibility of a reverse reaction in DASA hydrolysis which has been long believed to be irreversible. PMID- 27397002 TI - Occurrence of Bound Salt in Freeze-concentrated Soy Sauce. AB - Part of the salt in soy sauce formed no eutectic H2O*2NaCl crystals at sub-zero temperatures and remained in a freeze-concentrated product. NMR line width of (23)Na was broader in the concentrated soy sauce than in the material. A broad line width of (23)Na was also observed in an aqueous solution of NaCl and a non diffusible soy sauce fraction. The data indicate that part of the salt in soy sauce interacted with its non-diffusible fraction and that such bound salt formed no eutectic crystals. PMID- 27397003 TI - Suppression of the SOS-Inducing Activity of Trp-P-1 and Aflatoxin B1 by Meso dihydroguaiaretic Acid from Machilus thunbergii in the Salmonella typhimurium TA1535/pSK1002 umu Test. AB - The methanol extract from Machilus thunbergii showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes. The methanol extract from M. thunbergii was successively re-extracted with chloroform, butanol and water. A suppressive compound in the chloroform extract fraction was isolated by SiO2 column chromatography and identified as meso-dihydroguaiaretic acid by GC-MS, and (1)H- and (13)C-NMR spectroscopy. Meso-dihydroguaiaretic acid inhibited of the SOS inducing activity of Trp-P-1 in the umu test. Gene expression was suppressed by 62% at less than 0.18 MUmol/ml, the ID50 value being 0.08 MUmol/ml. Compound 1 was also assayed with aflatoxin B1 (AfB1) and showed a suppressive effect. PMID- 27397004 TI - Ornatipolide, a Novel Phenolic Metabolite from the Basidiomycete, Boletus ornatipes. AB - A novel phenolic metabolite, ornatipolide, was isolated from the Boletus ornatipes fungus. Its structure was established by a combination of spectroscopic and chemical methods, and by an X-ray crystallographic analysis. PMID- 27397005 TI - Lipase-catalyzed Kinetic Resolution of (+/-)-cis,cis-Spiro[4.4]nonane-1,6-diol. AB - (+/-)-cis,cis-Spiro[4.4]nonane-1,6-diol (1), which has axial chirality, was efficiently resolved by lipase-catalyzed enantioselective esterification in diisopropyl ether. PMID- 27397006 TI - Comparison of Volatile Compounds from Chungkuk-Jang and Itohiki-Natto. AB - Volatile compounds from two South-East Asian fermented soybean foods, Chungkuk jang (CKJ) and Itohiki-natto (natto), were analysed by gas chromatography-mass spectrometry (GC-MS), gas chromatography (GC), and GC-sniffing. A total of 112 compounds were identified. A large amount of ethanol was detected from CKJ, while acetone and methyl isobutyrate were major components of natto. The characteristic odor compounds of CKJ were some ethyl esters of short chain fatty acids, diallyl disulfide, and several natto-like odor compounds were identified as ammonia, 2,5 dimethylpyrazine, and 2-methylbutanoic acid. PMID- 27397007 TI - Effect of Jasmonates and Related Compounds on Seed Germination of Orobanche minor Smith and Striga hermonthica (Del.) Benth. AB - Jasmonates and related compounds were found to elicit the seed germination of the important root parasites, clover broomrape (Orobanche minor Smith) and witchweed [Striga hermonthica (Del.) Benth]. The stimulation of seed germination by the esters was more effective than by the corresponding free acids, and methyl jasmonate (MJA) was the most active stimulant among the compounds tested. PMID- 27397008 TI - Acetylation of Bacterial Cellulose: Preparation of Cellulose Acetate Having a High Degree of Polymerization. AB - Cellulose triacetate prepared from bacterial cellulose of Acetobacter xylinum subsp. sucrofermentans BPR3001A showed a higher degree of polymerization and higher mechanical strength than that from the cotton linter. The fine fibrils of bacterial cellulose required only a short time for acetylation which preserved the high degree of polymerization. PMID- 27397009 TI - Stereochemical Difference in Secoisolariciresinol Formation between Cell-free Extracts from Petioles and from Ripening Seeds of Arctium lappa L. AB - Cell-free extracts from ripening seeds of Arctium lappa L. catalyzed the enantioselective formation of (-)-pinoresinol, (-)-lariciresinol and (-) secoisolariciresinol from achiral coniferyl alcohol in the presence of NADPH and H2O2. The enantioselectivity of the lignan formation was opposite to that of the (+)-secoisolariciresinol formation catalyzed by cell-free extracts from petioles of the same plant species. PMID- 27397010 TI - ATP cost of muscle contraction is associated with motor unit discharge rate in humans. AB - Although a neural component has been suggested to contribute to the energetic cost of muscle contraction in vivo, the association between neural and energetic factors has not been determined during voluntary contractions in humans. Twenty young (24+/-1years, 10 women) healthy individuals performed isometric ankle dorsiflexion contractions at 20%, 50% and 100% of maximal voluntary contraction torque on two occasions during which measures of either motor unit discharge rates (MUDR, by indwelling electromyography) or ATP cost of contraction (by (31)P magnetic resonance spectroscopy) were obtained. Both MUDR and ATP cost increased with increasing contraction intensity (p<=0.02). A strong, positive relationship (r(2)=0.70; p<0.001) was observed between MUDR and ATP cost. These results suggest that a substantial portion of the variability in ATP cost can be explained by MUDR, and thus demonstrate that motor unit rate coding is likely an important neural factor contributing to energetic cost in vivo. PMID- 27397011 TI - Mutations in glucocerebrosidase are a major genetic risk factor for Parkinson's disease and increase susceptibility to dementia in a Flanders-Belgian cohort. AB - OBJECTIVE: To investigate the frequency of glucocerebrosidase (GBA) mutations in a Flanders-Belgian Parkinson's disease (PD) patient cohort and to assess genotype phenotype correlations. METHODS: We performed an in-depth sequencing of all coding exons of GBA in 266 clinically well-characterized PD patients and 536 healthy control individuals. RESULTS: We identified rare, heterozygous GBA mutations in 12 PD patients (4.5%) and in 2 healthy control individuals (0.37%), confirming the genetic association of GBA mutations with PD in the Flanders Belgian population (p<0.001). The patient carriers had a more severe Unified Parkinson's Disease Rating Scale (UPDRS) motor score than non-carriers. Also, GBA mutation status was a significant, independent predictor for the presence of dementia (OR=12.43, 95% CI: 2.27-68.14. p=0.004). Genetic association of PD with the common p.E326K and p.T369M variants in GBA was absent. CONCLUSION: In our Flanders-Belgian cohort, carrier status of a heterozygous GBA mutation was a strong genetic risk factor for PD. The GBA mutation frequency of 4.5% is comparable to previously reported data in other European PD patient cohorts. Furthermore, our clinical data suggest a more severe motor phenotype and a strong predisposition to dementia in GBA mutation carriers. PMID- 27397012 TI - Posturographic destabilization in eating disorders in female patients exposed to body image related phobic stimuli. AB - Human postural control is dependent on the central integration of vestibular, visual and proprioceptive inputs. Psychological states can affect balance control: anxiety, in particular, has been shown to influence balance mediated by visual stimuli. We hypothesized that patients with eating disorders would show postural destabilization when exposed to their image in a mirror and to the image of a fashion model representing their body ideal in comparison to body neutral stimuli. Seventeen females patients attending a day centre for the treatment of eating disorders were administered psychometric measures of body dissatisfaction, anxiety, depression and underwent posturographic measures with their eyes closed, open, watching a neutral stimulus, while exposed to a full length mirror and to an image of a fashion model corresponding to their body image. Results were compared to those obtained by eighteen healthy subjects. Eating disordered patients showed higher levels of body dissatisfaction and higher postural destabilization than controls, but this was limited to the conditions in which they were exposed to their mirror image or a fashion model image. Postural destabilization under these conditions correlated with measures of body dissatisfaction. In eating disordered patients, body related stimuli seem to act as phobic stimuli in the posturographic paradigm used. If confirmed, this has the potential to be developed for diagnostic and therapeutic purposes. PMID- 27397014 TI - Conflicting Study Results. PMID- 27397013 TI - Improving Treatment Adherence in Heart Failure. AB - BACKGROUND: Despite improved treatment options, heart failure remains the third most common cause of death in Germany and the most common reason for hospitalization. The treatment recommendations contained in the relevant guidelines have been incompletely applied in practice. The goal of this systematic review is to study the efficacy of adherence-promoting interventions for patients with heart failure with respect to the taking of medications, the implementation of recommended lifestyle changes, and the improvement in clinical endpoints. METHODS: We performed a meta-analysis of pertinent publications retrieved by a systematic literature search. RESULTS: 55 randomized controlled trials were identified, in which a wide variety of interventions were carried out on heterogeneous patient groups with varying definitions of adherence. These trials included a total of 15 016 patients with heart failure who were cared for as either inpatients or outpatients. The efficacy of interventions to promote adherence to drug treatment was studied in 24 trials; these trials documented improved adherence in 10% of the patients overall (95% confidence interval [CI]: [5; 15]). The efficacy of interventions to promote adherence to lifestyle recommendations was studied in 42 trials; improved adherence was found in 31 trials. Improved adherence to at least one recommendation yielded a long-term absolute reduction in mortality of 2% (95% CI: [0; 4]) and a 10% reduction in the likelihood of hospitalization within 12 months of the start of the intervention (95% CI: [3; 17]). CONCLUSION: Many effective interventions are available that can lead to sustained improvement in patient adherence and in clinical endpoints. Longterm success depends on patients' assuming responsibility for their own health and can be achieved with the aid of coordinated measures such as patient education and regular follow-up contacts. PMID- 27397015 TI - A Comparison of Responders and Nonresponders Is Lacking. PMID- 27397016 TI - In Reply. PMID- 27397017 TI - Incorporation of Delirium Prevention in Palliative Medicine. PMID- 27397018 TI - Recommendations Require Critical Appraisal in Individual Cases. PMID- 27397019 TI - In Reply. PMID- 27397020 TI - Breastfeeding and Complementary Feeding. AB - BACKGROUND: Proper infant nutrition promotes healthy growth and development and lowers the risk of disease in later life. METHODS: This review is based on pertinent articles retrieved by a selective search, including guidelines, meta analyses, and systematic reviews. RESULTS: Infants should be exclusively breast fed until at least the age of 4 months. Infants who are no longer being breast fed, or no longer exclusively so, should be given commercially available low protein infant formula containing long-chain polyunsaturated fatty acids. Infants with a family history of allergy should be fed with infant formula based on hydrolyzed protein until complementary feeding begins. Complementary feeding should be initiated no earlier than the beginning of the 5th month and no later than the beginning of the 7th; it should include iron derived from meat, as well as fish once or twice a week. Later initiation of complementary feeding is associated with an increased risk of allergies and is not recommended. Ordinary cow's milk should not be drunk in the first year of life. All infants should be given 2 mg of vitamin K at birth, at 7-10 days, and at 4-6 weeks of age, as well as daily oral supplementation of vitamin D (400-500 IE) and fluoride (0.25 mg). CONCLUSION: Physicians should advise families about healthful infant nutrition in order to lay the foundation for lifelong good health through a proper diet. PMID- 27397021 TI - Effect of reaction temperature on the size and morphology of scorodite synthesized using ultrasound irradiation. AB - Synthesis of scorodite (FeAsO4.2H2O) using dynamic action agglomeration and the oxidation effect from ultrasound irradiation was investigated. The effect of different reaction temperatures (90, 70, 50, and 30 degrees C) on the size and morphology of scorodite particles synthesized under O2 gas flow and ultrasound irradiation was explored because the generation of fine bubbles depends on the solution temperature. At 90 degrees C, the size of scorodite particles was non homogeneous (from fine particles (<1MUm) to large particles (>10MUm)). The oxidation-reduction potential (ORP) and yield at 90 degrees C showed lower values than those at 70 degrees C. The scorodite particles, including fine and non homogeneous particles, were generated by a decrease in the oxidation of Fe(II) to Fe(III) and promotion of dissolution caused by the generation of radicals and jet flow from ultrasound irradiation. Using ultrasound irradiation in the synthesis of scorodite at low temperature (30 degrees C) resulted in the appearance of scorodite peaks in the X-ray diffraction (XRD) pattern after a reaction time of 3h. The peaks became more intense with a reaction temperature of 50 degrees C and crystalline scorodite was obtained. Therefore, ultrasound irradiation can enable the synthesis of scorodite at 30 degrees C as well as the synthesis of large particles (>10MUm) at higher temperature. Oxide radicals and jet flow generated by ultrasound irradiation contributed significantly to the synthesis and crystal growth of scorodite. PMID- 27397022 TI - Assessment of Added Value of Noncontrast to Contrast-Enhanced Abdominal Computed Tomography Scan for Characterization of Hypervascular Liver Metastases. AB - Assess the added value of nonenhanced computed tomography (NECT) to contrast enhanced CT (CECT) of the abdomen for characterization of hypervascular liver metastases and incidental findings. Institutional review board approved, Health Insurance Probability and Accountability Act compliant, retrospective study of patients with melanoma, neuroendocrine tumor, or thyroid cancer. First available triphasic abdomen CT after initial diagnosis was reviewed by 3 radiologists. The 3 most suspicious lesions were characterized on the CECT as benign or malignant and then recharacterized after reviewing the NECT with CECT. Incidental renal and adrenal lesions were characterized similarly. Diagnostic performance of CECT vs its combination with NECT was assessed. Statistical significance level was set at P < 0.05. A total of 81 patients were included (mean age = 55 years; 52% male; 64% with liver lesions; 27% and 11% with incidental renal and adrenal lesions, respectively). Percentage area under the curve and 95% CI of CECT vs combination with NECT for characterization of liver metastases was 98(94-100) vs 99(96-100) for reviewer 1 (P = 0.35), 93(86-100) vs 94(87-100) for reviewer 2 (P = 0.23), and 96(90-100) vs 99(97-100) for reviewer 3 (P = 0.32). Mean difference in area under the curve and 95% CI between 2 protocols for characterization of liver, renal, and adrenal lesions were -0.007(-0.05 to 0.04) (P = 0.63), -0.09(-0.25 to 0.07) (P = 0.22), and -0.01(-0.05 to 0.02) (P = 0.27), respectively. After addition of NECT, confidence level for lesion characterization increased 4%-15% for liver metastases, 18%-59% and 33%-67% for renal and adrenal lesions, respectively. In conclusion, while addition of NECT to CECT improved radiologist' confidence, there was no statistically significant change in characterization of hypervascular liver metastases or incidental renal and adrenal lesions. PMID- 27397023 TI - Risk of death following admission to a UK hospital with diabetic ketoacidosis. AB - AIMS/HYPOTHESIS: The aim of this study was to assess the risk of death during hospital admission for diabetic ketoacidosis (DKA) and, subsequently, following discharge. In addition, we aimed to characterise the risk factors for multiple presentations with DKA. METHODS: We conducted a retrospective cohort study of all DKA admissions between 2007 and 2012 at a university teaching hospital. All patients with type 1 diabetes who were admitted with DKA (628 admissions of 298 individuals) were identified by discharge coding. Clinical, biochemical and mortality data were obtained from electronic patient records and national databases. Follow-up continued until the end of 2014. RESULTS: Compared with patients with a single DKA admission, those with recurrent DKA (more than five episodes) were diagnosed with diabetes at an earlier age (median 14 [interquartile range 9-23] vs 24 [16-34] years, p < 0.001), had higher levels of social deprivation (p = 0.005) and higher HbA1c values (103 [89-108] vs 79 [66 96] mmol/mol; 11.6% [10.3-12.0%] vs 9.4% [8.2-10.9%], p < 0.001), and tended to be younger (25 [22-36] vs 31 [23-42] years, p = 0.079). Antidepressant use was greater in those with recurrent DKA compared with those with a single episode (47.5% vs 12.6%, p = 0.001). The inpatient DKA mortality rate was no greater than 0.16%. A single episode of DKA was associated with a 5.2% risk of death (4.1 [2.8 6.0] years of follow-up) compared with 23.4% in those with recurrent DKA admissions (2.4 [2.0-3.8] years of follow-up) (HR 6.18, p = 0.001). CONCLUSIONS/INTERPRETATION: Recurrent DKA is associated with substantial mortality, particularly among young, socially disadvantaged adults with very high HbA1c levels. PMID- 27397024 TI - Organ preservation with chemoradiation in advanced laryngeal cancer: The problem of generalizing results from randomized controlled trials. AB - BACKGROUND: The primary goal of treatment in advanced laryngeal cancer is to achieve optimal oncologic outcomes while preserving function and quality of life. Combination of chemotherapy and radiation has been popularized as an alternative to surgery for patients facing total laryngectomy. However, survival analyses from large, population-based databases have not duplicated results reported from randomized trials. METHODS: A comprehensive literature review was undertaken to try to better understand the reasons why results differ among randomized trials and population cohort studies. RESULTS: A variety of reasons are discussed, including differences in patient staging, selection bias, complexity bias, inconsistent terminology, patient compliance and treatment expertise. CONCLUSIONS: Personalized treatment considering all factors is critical for optimal outcomes. In general, evidence supports total laryngectomy for patients with T4 cancers. Definitive chemoradiotherapy strategies are acceptable alternatives for T3 cancers, provided that all resources for the administration of the treatment, follow-up and surgical salvage are available. PMID- 27397026 TI - Carbon dioxide capture strategies from flue gas using microalgae: a review. AB - Global warming and pollution are the twin crises experienced globally. Biological offset of these crises are gaining importance because of its zero waste production and the ability of the organisms to thrive under extreme or polluted condition. In this context, this review highlights the recent developments in carbon dioxide (CO2) capture from flue gas using microalgae and finding the best microalgal remediation strategy through contrast and comparison of different strategies. Different flue gas microalgal remediation strategies discussed are as follows: (i) Flue gas to CO2 gas segregation using adsorbents for microalgal mitigation, (ii) CO2 separation from flue gas using absorbents and later regeneration for microalgal mitigation, (iii) Flue gas to liquid conversion for direct microalgal mitigation, and (iv) direct flue gas mitigation using microalgae. This work also studies the economic feasibility of microalgal production. The study discloses that the direct convening of flue gas with high carbon dioxide content, into microalgal system is cost-effective. PMID- 27397025 TI - Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells. AB - The precise identity of a tumour's cell of origin can influence disease prognosis and outcome. Methods to reliably define tumour cell of origin from primary, bulk tumour cell samples has been a challenge. Here we use a well-defined model of MLL rearranged acute myeloid leukaemia (AML) to demonstrate that transforming haematopoietic stem cells (HSCs) and multipotent progenitors results in more aggressive AML than transforming committed progenitor cells. Transcriptome profiling reveals a gene expression signature broadly distinguishing stem cell derived versus progenitor cell-derived AML, including genes involved in immune escape, extravasation and small GTPase signal transduction. However, whole-genome profiling of open chromatin reveals precise and robust biomarkers reflecting each cell of origin tested, from bulk AML tumour cell sampling. We find that bulk AML tumour cells exhibit distinct open chromatin loci that reflect the transformed cell of origin and suggest that open chromatin patterns may be leveraged as prognostic signatures in human AML. PMID- 27397027 TI - Characterising the hydrological regime of an ungauged temporary river system: a case study. AB - Temporary streams are characterised by specific hydrological regimes, which influence ecosystem processes, groundwater and surface water interactions, sediment regime, nutrient delivery, water quality and ecological status. This paper presents a methodology to characterise and classify the regime of a temporary river in Southern Italy based on hydrological indicators (HIs) computed with long-term daily flow records. By using a principal component analysis (PCA), a set of non-redundant indices were identified describing the main characteristics of the hydrological regime in the study area. The indicators identified were the annual maximum 30- and 90-day mean (DH4 and DH5), the number of zero flow days (DL6), flow permanence (MF) and the 6-month seasonal predictability of dry periods (SD6). A methodology was also tested to estimate selected HIs in ungauged river reaches. Watershed characteristics such as catchment area, gauging station elevation, mean watershed slope, mean annual rainfall, land use, soil hydraulic conductivity and available water content were derived for each site. Selected indicators were then linked to the catchment characteristics using a regression analysis. Finally, MF and SD6 were used to classify the river reaches on the basis of their degree of intermittency. The methodology presented in this paper constitutes a useful tool for ecologists and water resource managers in the Water Framework Directive implementation process, which requires a characterisation of the hydrological regime and a 'river type' classification for all water bodies. PMID- 27397029 TI - Analysis of energy-related CO2 emissions and driving factors in five major energy consumption sectors in China. AB - Continual growth of energy-related CO2 emissions in China has received great attention, both domestically and internationally. In this paper, we evaluated the CO2 emissions in five major energy consumption sectors which were evaluated from 1991 to 2012. In order to analyze the driving factors of CO2 emission change in different sectors, the Kaya identity was extended by adding several variables based on specific industrial characteristics and a decomposition analysis model was established according to the LMDI method. The results demonstrated that economic factor was the leading force explaining emission increase in each sector while energy intensity and sector contribution were major contributors to emission mitigation. Meanwhile, CO2 emission intensity had no significant influence on CO2 emission in the short term, and energy consumption structure had a small but growing negative impact on the increase of CO2 emissions. In addition, the future CO2 emissions of industry from 2013 to 2020 under three scenarios were estimated, and the reduction potential of CO2 emissions in industry are 335 Mt in 2020 under lower-emission scenario while the CO2 emission difference between higher-emission scenario and lower-emission scenario is nearly 725 Mt. This paper can offer complementary perspectives on determinants of energy related CO2 emission change in different sectors and help to formulate mitigation strategies for CO2 emissions. PMID- 27397030 TI - If you suffer from type-2 diabetes mellitus, your ERCP is likely to have a better outcome. AB - Editorial dealing with the protective action on biliary sphincterotomy complications given by type 2 diabetes mellitus. PMID- 27397028 TI - (Anti-)estrogenic and (anti-)androgenic effects in wastewater during advanced treatment: comparison of three in vitro bioassays. AB - Endocrine-disrupting chemicals are mainly discharged into the environment by wastewater treatment plants (WWTPs) and are known to induce adverse effects in aquatic life. Advanced treatment with ozone successfully removes such organic micropollutants, but an increase of estrogenic effects after the ozonation of hospital wastewater was observed in previous studies. In order to investigate this effect, estrogenic and androgenic as well as anti-estrogenic and anti androgenic activities were observed during treatment of hospital wastewater using three different effect-based reporter gene bioassays. Despite different matrix influences, sensitivities, and test-specific properties, all assays used obtained comparable results. Estrogenic and androgenic activities were mainly reduced during the biological treatment and further removed during ozonation and sand filtration, resulting in non-detectable agonistic activities in the final effluent. An increased estrogenic activity after ozonation could not be observed in this study. Antagonistic effects were removed in the biological treatment by up to 50 % without further reduction in the advanced treatment. Due to the presence of antagonistic substances within the wastewater, masking effects were probable. Therefore, this study showed the relevance of antagonistic activities at hospital WWTPs and illustrates the need for a better understanding about antagonistic effects. PMID- 27397031 TI - Identification of a key role for permeability glycoprotein in enhancing the cellular defense mechanisms of fertilized oocytes. AB - Double strand breaks (DSBs) are highly damaging DNA lesions that can destabilize the genome and generate a suite of adverse physiological outcomes in the oocyte and early embryo. While it is therefore likely that these cells possess a sophisticated suite of protective mechanisms to ameliorate such damage, the precise nature of these defense systems are yet to be fully elucidated. This study characterizes the sensitivity of the oocyte to etoposide, a chemotherapeutic agent with the ability to elicit DSBs. We demonstrate significant developmental changes in etoposide vulnerability, with fertilization of the oocyte leading to an enhancement of its cellular defense machinery. Using a parthenogenic model we show that this response is mediated, at least in part, by permeability glycoprotein (PGP), an endogenous multidrug efflux transporter that is up-regulated, translocated to the oolemma and phosphorylated upon oocyte activation. Moreover, evidence from dye exclusion assays in the presence of a specific PGP pharmacological inhibitor (PSC833), illustrates that these events effectively increase oocyte efflux activity, thereby enhancing the ability of these cells to exclude genotoxicants capable of eliciting DSB formation. PMID- 27397032 TI - The Effect of Different microRNA Backbones on Artificial miRNA Expression and Knockdown Activity Against HIV-1 Replication. AB - BACKGROUND: Artificial microRNAs (miRNAs) are designed to develop an RNAi-based gene therapy. Recently, it has been suggested that the flanking sequences and terminal loop structure play a critical role in RNAi biogenesis and target recognition, but no extensive study regarding the different miRNA backbone for artificial miRNAs optimization has been conducted. OBJECTIVE: We tested three artificial miRNAs with human hsa-miR30a (common miRNA), hsa-miR150 (T cell specific miRNA), and hsa-miR122 (liver specific miRNA) backbones in HEK-293T and Jurkat cell lines. METHODS: Artificial miRNA processing and knockdown efficiency were analyzed by stem-loop RT-PCR, qRT-PCR, luciferase assay and target challenging. RESULTS: We identified strikingly different RNAi activities among these different artificial miRNAs. Our results demonstrated that expression and function of art-miR150 was more than art-miR30 and artmiR122 in both HEK-293T and Jurkat cell lines. Since the main difference in these artificial miRNAs was flanking sequences and terminal loop structure, the change between the expression and function of artificial miRNAs can be attributed to these structures. CONCLUSION: This study showed that expression of cell-specific artificial miRNA in target and nontarget cells is not different, but variation in flanking sequences and terminal loop can be involved in expression and function of artificial miRNAs. These results can be important for improving artificial miRNA design in RNAi-based gene therapy. PMID- 27397033 TI - MicroRNAs: Modulators of Tooth Development. AB - MicroRNAs (miRNAs) are non-coding RNAs that are involved in various biological pathways by regulating gene expression. Teeth develop via reciprocal and sequential interactions between the epithelium and the ectomesenchyme. The speci.c functions of several genes during tooth development are known, and the involvement of their mutations in the pathogenesis of congenital dental defects has been widely studied. The miRNA pathway is considered to have a significant role in embryogenesis including tooth development. It has been shown that miRNAs regulate morphogenesis of tooth by fine-tuning the signalling networks, however, their precise role in tooth differentiation and morphogenesis is still elusive. The present review focuses on the studies that have used animal models to explore the function of miRNAs in tooth development. Major findings with special emphasis on the miRNA involvement in .ne-tuning and network regulation are presented and discussed. Disturbances in tooth development in the global miRNA processing knockouts mirror the essential fine-tuning guiding appropriate formation of dental hard tissues. However, further investigation of single miRNA function and mutation, including deletion and overexpression, may lead to improved knowledge on development of particular dental defects in humans. In the light of similarities between tooth development and other organs originating from the epithelium, further understanding of miRNAs' function during tooth development may have wide biological relevance. PMID- 27397034 TI - Laparoscopy-assisted transjejunal ERCP in a patient with roux-en-Y gastric bypass. AB - In the case of Roux-en-Y gastric bypass with a long afferent limb, the need to carry out an ERCP still represents a technical challenge. In this article we describe the case of a 50-year-old male admitted to the ER for abdominal pain in the right upper quadrant, in the context of prior Roux-en-Y gastric bypass (4 years ago), with uncomplicated gallbladder stones discovered 3 months ago. The patient presented recurrent abdominal pain for 3 months but in the last few days the pain became continuous. The blood test revealed elevation of hepatic enzymes and bilirubin levels. The US findings were uncomplicated gallbladder lithiasis with no signs of lithiasic migration in the common bile duct, despite strong clinical suspicion and positive MRI 3 weeks before. We decided therefore to perform a laparoscopic cholecystectomy with perioperative cholangiography and a laparoscopy-assisted transjejunal ERCP through a jejunostomy 80 cm distal to the ligament of Treitz, allowed us to successfully carry out sphincterotomy and extraction of a 10mm lithiasis from the common bile duct. PMID- 27397035 TI - Appendiceal inflammatory myofibroblastic tumor: a rare postoperative finding. AB - Inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue neoplasm of unknown etiology. It mimics, clinically and radiologically, malignant tumors. Histologically, this tumor is composed of differentiated myofibroblastic spindle cells accompanied by an inflammatory infiltrate, with numerous plasma cells and/or lymphocytes. Initially described in the lung, numerous extrapulmonary sites of this tumor have been found but appendiceal IMT is rare, especially in adult women. In this study, we aimed to examine the literature as well as to describe a case of a 42-year-old woman that we operated on that presented as an appendiceal mass that obstructed the lumen of the appendix and caused acute appendicitis. Upon histopathological examination, the lesion was identified as an IMT. Awareness of this type of tumor in the differential diagnosis of appendiceal masses, avoids overtreatment, and highlights the need of long-term follow-up regarding the tendency for local recurrence and small risk of distant metastasis. PMID- 27397036 TI - Traumatic herniation of the lung. AB - We present a relatively rare clinical presentation of herniation of lung parenchyma. In our case, the patient suffered multiple rib fractures, with an intercostal herniation of lung tissue after a trauma. We opted for a conservative treatment, given the clinical presentation, and the absence of incarceration or strangulation of the pulmonary tissue. In the absence of clear guidelines for this rare presentation, current treatment can be conservative or surgical, depending on the clinical presentation. PMID- 27397037 TI - Gastrocnemius fascia release under local anaesthesia as a treatment for neuropathic foot ulcers in diabetic patients: a short series. AB - BACKGROUND: Diabetic foot ulceration is the leading cause of major amputation in the developed world. Plantar neuropathic ulcers at the forefoot can be managed conservatively with off-loading, but treatment is not invariably successful. Achilles tendon lengthening procedures aim at increasing dorsiflexion and decreasing forefoot pressure but can be associated with complications and require prolonged postoperative immobilization to prevent tendon rupture. We assessed the feasibility and clinical outcome of a comparative minimal invasive procedure: the gastrocnemius fascia release. This technique targets the same goals but is performed under local anaesthesia and allows immediate postoperative weight bearing and ambulation. METHODS: Diabetic patients with plantar neuropathic ulcers Wagner grade 2 or 3 were recruited from our diabetic foot clinic. Patients with infected wounds or untreatable peripheral arterial disease were excluded from the study. Conservative treatment with off-loading and local wound care was attempted for six weeks and surgical procedure only contemplated upon failure. Primary end-points were improved range of dorsiflexion and time to healing. Secondary end-points were local ulcer recurrences, new plantar ulcers, and minor or major amputation. Post-operative follow-up was 12 months. RESULTS: Seven patients were included in the study. An improvement in dorsiflexion of 10.4 degrees (mean) was recorded post-operatively (p < 0.01). After 30 days, complete healing was accomplished in six of the seven patients. Long-term results were excellent as no ulcer recurrence or amputation was noted. CONCLUSIONS: Gastrocnemius fascia release under local anaesthesia can be performed safely in diabetic patients with plantar neuropathic ulcers under the metatarsal heads. Clinical outcome is excellent and long-term results promising. PMID- 27397038 TI - Linitis plastica of the bypassed stomach 7 years after Roux-en-Y gastric bypass: a case report. AB - Laparoscopic Roux-en-Y gastric bypass (RYGB) is currently the preferred surgical procedure to treat morbid obesity. It has proven its effects on excess weight loss and its positive effect on comorbidities. One of the main issues, however, is the post-operative evaluation of the bypassed gastric remnant. In literature, cancer of the excluded stomach after RYGB is rare. We describe the case of a 52 year-old woman with gastric linitis plastica in the bypassed stomach after Roux en-Y gastric bypass, diagnosed by means of laparoscopy and Single-Balloon enteroscopy, and it is clinical importance. Linitis plastica of the excluded stomach after RYGB is a very rare entity. This case report shows the importance of long-term post-operative follow-up, and the importance of single-balloon enteroscopy for visualization of the bypassed stomach remnant, when other investigations remain without results. This case report is only the second report of a linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass. PMID- 27397039 TI - Corrigendum to "Evaluation of the effect on patient parameters of not monitoring gastric residual volume in intensive care patients on a mechanical ventilator receiving enteral feeding: a randomized clinical trial." J Crit Care 2016(33):137 144. PMID- 27397041 TI - BRCA mutations and risk of uterine cancer. PMID- 27397042 TI - ESMO World Congress on Gastrointestinal Cancer 2016. PMID- 27397040 TI - Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. AB - BACKGROUND: About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48.6 Gy) in 1.8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. FINDINGS: Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for health-related quality of life. Median follow-up was 42.3 months (IQR 25.8-55.1). At completion of radiotherapy and at 6 months, EORTC QLQ-C30 functioning scales were significantly lower (worse functioning) and health related quality of life symptom scores higher (worse symptoms) for the chemoradiotherapy group compared with radiotherapy alone, improving with time. At 12 and 24 months, global health or quality of life was similar between groups, whereas physical functioning scores remained slightly lower in patients who received chemoradiotherapy compared with patients who received radiotherapy alone. At 24 months, 48 (25%) of 194 patients in the chemoradiotherapy group reported severe tingling or numbness compared with 11 (6%) of 170 patients in the radiotherapy alone group (p<0.0001). Grade 2 or worse adverse events were found during treatment in 309 (94%) of 327 patients in the chemoradiotherapy group versus 145 (44%) of 326 patients in the radiotherapy alone group, and grade 3 or worse events were found in 198 (61%) of 327 patients in the chemoradiotherapy group versus 42 (13%) of 326 patients in the radiotherapy alone group (p<0.0001), with most of the grade 3 adverse events being haematological (45%). At 12 and 24 months, no significant differences in grade 3 or worse adverse events were found between groups; only grade 2 or higher sensory neuropathy adverse events persisted at 24 months (25 [10%] of 240 patients in the chemoradiotherapy group vs one [<1%] of 247 patients in the radiotherapy alone group; p<0.0001). INTERPRETATION: Despite the increased physician and patient-reported toxicities, this schedule of adjuvant chemotherapy given during and after radiotherapy in patients with high-risk endometrial cancer is feasible, with rapid recovery after treatment, but with persistence of patient-reported sensory neurological symptoms in 25% of patients. We await the analysis of primary endpoints before final conclusions are made. FUNDING: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and Canadian Cancer Society Research Institute. PMID- 27397043 TI - Pembrolizumab for classical Hodgkin's lymphoma. PMID- 27397044 TI - Combined modality adjuvant therapy for high-risk endometrial cancer. PMID- 27397046 TI - Editor's Introduction. PMID- 27397045 TI - Complications in using the vertical expandable prosthetic titanium rib (VEPTR) in children. AB - PURPOSE: This report describes complications using the vertical expandable prosthetic titanium rib (VEPTR) for thoracic insufficiency syndrome (TIS) at a single center. METHODS: This is a prospective cohort evaluating 65 patients with rib-rib and rib-spine VEPTR devices for TIS placed between 10/2001 and 11/2014, for children with spinal or chest wall deformity. Patients were classified using the early onset scoliosis classification system (C-EOS). RESULTS: 65 patients are available for follow up. 23 congenital scoliosis, 12 neuromuscular, 14 syndromic, 2 idiopathic and 14 not classifiable by the C-EOS system including 11 chest wall reconstructions. Average age at implantation was 6.9years (range 1.3-24.8) with average follow up 6.9years (range 0.4-14.8). 22 patients had 37 complications. Those classifiable by C-EOS had complications in the normo- and hyperkyphotic groups. Implant erosion and infection were most common. The majority of complications required one additional unplanned surgery for resolution. Two complications required abandonment of a growth-friendly strategy. CONCLUSIONS: Use of VEPTR for TIS is associated with significant and frequent complications. C EOS suggests that complications are more likely in those with normal or hyperkyphotic curves. Most complications are managed with one unplanned surgery. VEPTR is usually salvaged and abandonment of a growth-friendly strategy is unusual. PMID- 27397047 TI - Adding Another Voice to the Living Donor Kidney Transplant Discussions at the CIBA Symposium of 1966. AB - In March 1966, the CIBA Foundation sponsored an international interdisciplinary conference on transplantation. Attendees included surgeons, physicians from many medical disciplines, legal professionals, a minister, and a science reporter. Although the main topic of discussion was the living donor, none was present. This article gives voice to the living donor through two qualitative interviews with men who donated at different centers in the United States in the early 1960s and subsequently developed end-stage renal disease (ESRD). These narratives contribute to five topics discussed at the CIBA meeting that are still relevant today: (1) pressure to donate; (2) special donor categories; (3) donor health; (4) socioeconomic consequences of donation; and (5) lack of regret. PMID- 27397048 TI - Escaping the Conceptual Analysis Straitjacket: Pathological Mechanisms and Canguilhem's Biological Philosophy. AB - This essay discusses four key criticisms recently leveled against the main attempts to use conceptual analysis to understand health and disease. First, it examines the weaknesses of these attempts and suggests a better way to proceed. Next, it briefly discusses another disease debate concerning pathological mechanisms and suggests that this approach could be more fruitful than that of conceptual analysis. The final section demonstrates how Georges Canguilhem's (1904-1995) biological philosophy of disease avoids some of the problems associated with conceptual analysis, and how he can contribute to both debates. Canguilhem's appeal to biological normativity is understood as contributing to a theoretical explanation, and a possible naturalization, of what is specific to healthy and pathological phenomena. PMID- 27397049 TI - "What an Affliction": Mary Todd Lincoln's Fatal Pernicious Anemia. AB - To date, no single diagnosis has unified the psychiatric illness and the numerous poorly defined physical complaints that Mary Lincoln (nee Todd, 1818-1882) suffered in adulthood. Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment. Long thought hypochondriacal, these findings, plus their time course and her psychopathology (irritability, delusions, hallucinations, with preserved clarity), are all consistent with vitamin B12 deficiency. Pernicious anemia most probably caused this deficiency: she lacked risk factors for other causes, and her consanguineous parents both derived from a region of Scotland having a high incidence of pernicious anemia. A diagnosis of chronic multisystem pernicious anemia would clarify the conduct of Mary Lincoln as First Lady and widow, and illuminate challenges faced by her husband, President Abraham Lincoln. Her case highlights many forgotten features of the natural history of untreated pernicious anemia and is unique in the medical literature in demonstrating such a course extending over a lifetime. PMID- 27397050 TI - Determination of Death: A Discussion on Responsible Scholarship, Clinical Practices, and Public Engagement. AB - The concept and determination of death by neurological or cardio-circulatory criteria play a crucial role for medical practice, society, and the law. Academic debates on death determination have regained momentum, and recent cases involving the neurological determination of death ("brain death") in the United States have sparked sustained public debate. The determination of death by neurological criterion (irreversible cessation of the whole brain or of the brain stem) is medically practiced in at least 80 countries. However, academic debates persist about the conceptual and scientific validity of death determined by neurological criterion. The cardio-circulatory criterion, which permits organ donation following cardio-circulatory arrest, has also recently been challenged. Given the presence of academic debates, several questions ensue about the responsible conduct of clinicians and scholars involved in clinical practices and academic research. This article identifies tension points for responsible practices in the domains of scholarship, clinical practice, and public discourse and formulates suggestions to stimulate further dialogue on responsible practices and to identify questions in need of further research. PMID- 27397051 TI - Vulnerability as the Human Condition. AB - An asymmetry at the heart of relationships between patients and health-care professionals places a particular moral weight on the side of the professionals-a responsibility to undermine conditions of vulnerability where possible in order to empower patients. This responsibility is best met by treating patients (and their families) as members of one and the same community that health-care professionals inhabit. A "pragmatic" approach to conditions of vulnerability in health care emphasizes the need to attend to the individuality of each patient and his or her vulnerabilities in order to help empower patients. PMID- 27397052 TI - Learn to Look and Be a Better Doctor. AB - Osler advised physicians to "learn to see." Visual intelligence, an ability to look carefully, to be attentive to the visible information in one's environment, and to articulate that information to others, is a skill that can be learned. Being a skilled observer, seeing the world the way an artist might see it, can make one into a more skilled physician. PMID- 27397053 TI - Electronic Medical Records and the Technological Imperative: The Retrieval of Dialogue in Community-Based Primary Care. AB - Electronic medical records are regarded as an important tool in primary health care settings. Because these records are thought to standardize medical information, facilitate provider communication, and improve office efficiency, many practices are transitioning to these systems. However, much of the concern with improving the practice of record keeping has related to technological innovations and human-computer interaction. Drawing on the philosophical reflection raised in Jacques Ellul's work, this article questions the technological imperative that may be supporting medical record keeping. Furthermore, given the growing emphasis on community-based care, this article discusses important non-technological aspects of electronic medical records that might bring the use of these records in line with participatory primary-care medicine. PMID- 27397054 TI - Montaigne on Medicine: Insights of a 16th-Century Skeptic. AB - Michel de Montaigne (1533-1592) viewed the medicine of his time with a well merited skepticism and had remarkable insight into its best resource, the placebo effect. Because less separates biomedicine from its Early Modern counterpart than commonly supposed, Montaigne still has much to tell us about the workings of this potent variable. When people improve as a result of surgery that did not take place, or for that matter sicken as a result of fumes that elude detection, they behave much like their counterparts in Montaigne's world. But doctors as well as patients are subject to errors of perception and inference. It was the goal of correcting misleading impressions by more reliable knowledge that led mid-20th century investigators of the placebo effect to propose the sort of methodologically demanding trials through which drugs are now run before being brought to market. Montaigne's awareness of the weak foundations of claimed knowledge, prominently including medical knowledge, was central to his philosophy of the human. PMID- 27397055 TI - On Changing One's Mind in Bioethics. AB - The legitimate scope of a legal option of physician-assisted death is a controversial issue. In this essay the author explains how he changed his mind over the course of 25 years of engaging with this issue and discusses some implications for thinking about the activity of bioethics scholarship. PMID- 27397056 TI - From Science to Writing: A Personal Perspective. AB - During my journey from scientist to writer, I confronted similar challenges. Scientists gather factual information to investigate Nature, but they also rely on narration and speculation to link discrete data points into a seamless story that fits current perspectives for acceptance; writers link specific events as steppingstones to write internally consistent stories that relate, however tenuously, to common experiences. The historical development of the gene concept exemplifies the narrative quality of science. Both science and writing, including fiction, always remain as works in progress. In addition to similarities, science and writing have complementary differences. Science involves performing experiments to resolve external mysteries of Nature; writing explores experiences to confront internal feelings. Scientists strive for meaningful conclusions, which are continually subject to change; writers, especially novelists, dwell in ambiguity and conflicts, which are never fully resolved. Taken together, I consider my efforts in science and writing as blended forms of creative self expression. PMID- 27397057 TI - Second Time. PMID- 27397058 TI - Anthophyllite asbestos: state of the science review. AB - Anthophyllite is an amphibole form of asbestos historically used in only a limited number of products. No published resource currently exists that offers a complete overview of anthophyllite toxicity or of its effects on exposed human populations. We performed a review focusing on how anthophyllite toxicity was understood over time by conducting a comprehensive search of publicly available documents that discussed the use, mining, properties, toxicity, exposure and potential health effects of anthophyllite. Over 200 documents were identified; 114 contained relevant and useful information which we present chronologically in this assessment. Our analysis confirms that anthophyllite toxicity has not been well studied compared to other asbestos types. We found that toxicology studies in animals from the 1970s onward have indicated that, at sufficient doses, anthophyllite can cause asbestosis, lung cancer and mesothelioma. Studies of Finnish anthophyllite miners, conducted in the 1970s, found an increased incidence of asbestosis and lung cancer, but not mesothelioma. Not until the mid 1990s was an epidemiological link with mesothelioma in humans observed. Its presence in talc has been of recent significance in relation to potential asbestos exposure through the use of talc-containing products. Characterizing the health risks of anthophyllite is difficult, and distinguishing between its asbestiform and non-asbestiform mineral form is essential from both a toxicological and regulatory perspective. Anthophyllite toxicity has generally been assumed to be similar to other amphiboles from a regulatory standpoint, but some notable exceptions exist. In order to reach a more clear understanding of anthophyllite toxicity, significant additional study is needed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27397059 TI - Seizures and Methemoglobinemia After Topical Application of Eutectic Mixture of Lidocaine and Prilocaine on a 3.5-Year-Old Child with Molluscum Contagiosum and Atopic Dermatitis. AB - A eutectic mixture of lidocaine and prilocaine (EMLA) is used topically to provide local anesthesia for a variety of painful superficial procedures. Although the side effects of EMLA are usually mild and transient local reactions, potentially life-threatening complications can occur. We report a case of generalized seizures and methemoglobinemia after topical application of EMLA for curettage of molluscum contagiosum lesions in a 3.5-year-old girl with atopic dermatitis. PMID- 27397060 TI - Effect of Glycemic Control on Chylomicron Metabolism and Correlation between Postprandial Metabolism of Plasma Glucose and Chylomicron in Patients with Type 2 Diabetes Treated with Basal-bolus Insulin Therapy with or without Vildagliptin. AB - AIM: Glucagon-like peptide-1 can reduce both postprandial plasma glucose (PG) and chylomicron (CM) levels in patients with type 2 diabetes. However, there have been no reports regarding the relationship between the postprandial metabolism of PG and CM. METHODS: Patients with type 2 diabetes who were admitted for glycemic control were randomized to insulin alone (Ins; n=16) or insulin plus vildagliptin 100 mg (InsV; n=16) groups. The insulin dose was adjusted to maintain normal blood glucose levels. The daily profiles of serum TG, remnant lipoprotein cholesterol (RemL-C), and apolipoprotein B48 (ApoB48) were estimated by frequent blood collection on admission and before discharge, and the daily glucose fluctuation profile was also estimated using continuous glucose monitoring (CGM) before discharge. RESULTS: The daily profiles of serum TG and RemL-C indicated a significant decrease before discharge compared with on admission; however, no significant changes in serum ApoB48 levels were observed in either group. At discharge, daily glucose fluctuation profile and the change in the serum ApoB48 level from fasting to the peak of the daily profile was significantly smaller in the InsV group than in the Ins group. The increment of serum ApoB48 level was significantly correlated with the mean amplitude of glycemic excursions calculated using CGM data only in the Ins group (R2= 0.5242,P<0.001). CONCLUSIONS: Short-term glycemic control decreased serum TG and RemL-C levels, but not ApoB48 levels, and the postprandial metabolism of PG and CM might be regulated by the same mechanism except GLP-1 effect. PMID- 27397061 TI - Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study. AB - AIM: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. METHODS: The study was a three arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. RESULTS: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean+/-SD changes in LDL cholesterol were -24.2%+/-14.7% with combination therapy, -16.0%+/-16.0% with fenofibrate alone, and -17.4%+/- 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p<0.01 for each). The corresponding values for triglycerides were -40.0%+/-29.5%, 40.1%+/-28.7%, and -3.4%+/-32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. CONCLUSION: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long term treatment in Japanese patients with combined hyperlipidemia. PMID- 27397062 TI - The Role of Gender-specific Cytokine Pathways as Drug Targets and Gender- specific Biomarkers in Personalized Cancer Therapy. AB - The definition of personalized treatments in tumor disease could lead to an improvement of the therapeutic success rate. Therefore, biomarkers are urgently required in order to select the patients that could benefit from adjuvant therapies in the initial phase of the disease and to better define and treat the clinical/therapeutic subgroups in the advanced pathological phases. Disregulation of cytokine physiological network is directly involved in the genesis and progression of tumors. Cytokines are of central importance in the regulation of immune system, but they are rarely released singly: each cytokine is able to induce the production of many other factors leading to a network in which they cooperate with other cell regulators such as hormones and neuropeptides. For these reasons the research must be directed to the evaluation of the interrelationships between the different cytokines and their respective pathways, as well as their contribution to the disease aetiology and progression in order to identify real and effective drug targets and biomarkers. The T CD4+ helper cells (Th) have various subpopulations, among which Th1, Th2, Th3, Th9 and Th17, respectively produce cytokines. It has become clear that disorders within the interactions of the network of these cytokines can produce neoplastic diseases. Furthermore, studies focusing on gender have shown that the homeostasis of the immune system is controlled by pathways of cytokines that are different between sexes and defined for this reason "genderspecifics". Therefore, this perspective article aims to highlight the significance of these cytokine pathways in order to identify new clinical strategies and personalized therapy in neoplastic diseases. PMID- 27397063 TI - Cardiac Tumors: Clinical Perspective and Therapeutic Considerations. AB - BACKGROUND: Cardiac tumors rare cardiac disorders with an overall incidence rate < 0.33%. Cardiac tumors can be classified as primary or secondary depending on the origins of tumors. Primary cardiac tumors (5% incidence) are rare compared with the secondary (95%, metastases of the heart) cardiac tumors. OBJECTIVE: Given that cardiac tumors exhibit some nonspecific symptoms compared with other heart diseases, clinical diagnosis of cardiac tumors is rather challenging. Thus we will try to review the classification and pathogenesis of cardiac tumors. CONCLUSION: Current evidence revealed that 75% of cardiac tumors are considered benign (myxoma, fibromas, lipomas, rhabdomyomas, hemangiomas, teratomas, papillary fibroelastomas, pericardial cysts or cystic tumor of atrioventricular node). Clinical differential diagnosis of cardiac tumors is mainly based on imaging techniques including transthoracic and transesophageal echocardiograms, computed tomography (CT) scans and magnetic resonance imaging (MRIs). This mini review tries to summarize recent understanding of the pathogenesis and therapeutics of cardiac tumors. PMID- 27397064 TI - GRANULOCYTE TRANSFUSION IN NEUTROPENIC PATIENTS-EBMT Educational Meeting from the Severe Aplastic Anaemia and Infectious Diseases Working Parties, Naples, Italy, 2014. AB - Neutropenic patients with malignancies and hematopoietic stem cell transplant recipients are prone to severe infections. Reversal of neutropenia with granulocyte transfusion (GTX) from donors stimulated with GCSF with/without steroids aims to improve outcome of infection. Cochrane analysis of randomized controlled studies, however, failed to show reduced mortality following GTX in conjunction with antibiotics. Non-randomized studies published during the last 20 years produced a very broad spectrum of results. The most important factors predicting favorable response to GTX are high number of granulocytes transfused and recovery from neutropenia. The response in patients with bad performance status, septic shock, multiple co-morbidities, multi-organ dysfunction and those in intensive care was poor. The response in fungal infections is generally worse than in bacterial infections. Cochrane analysis of prospective GTX clinical trials in preventing infection also failed to show reduced overall mortality. Adverse reactions in recipients are usually mild, although severe reactions, including respiratory deterioration, have been observed. Based on current evidence, GTX, at the amount at least 1x1010 per dose, can be considered in certain patients with severe neutropenia or congenital disorder of neutrophil function with proven or highly probable fungal or bacterial infection unresponsive to appropriate antimicrobial therapy with expected duration of neutropenia for at least 5 days; in cases where neutrophil recovery is anticipated. PMID- 27397065 TI - Targeted Temperature Management in Spontaneous Intracerebral Hemorrhage: A Systematic Review. AB - BACKGROUND: Fever is common in neurocritical care patients and is associated with poor outcome. Targeted temperature management (TTM), i.e. therapeutic hypothermia or controlled normothermia, after acute brain injury has been studied as a neuroprotectant for several decades. In contrast to pharmacological agents with specific targets TTM affects multiple pathophysiological mechanisms and is primarily thought to attenuate secondary brain injury. Most promising results have been obtained from experimental studies on cerebral ischemia or traumatic brain injury showing beneficial effects of hypothermia on structural and functional outcome. OBJECTIVE: The aim of this systematic review of the literature is to provide an overview on preclinical and clinical data on the use of TTM for intracerebral hemorrhage (ICH). The impact of TTM on structural changes and functional outcome after induced and spontaneous ICH will be summarized. RESULTS AND DISCUSSION: A positive influence of hypothermia has been observed in animal models of spontaneous ICH improving, among others, perihematomal edema, blood-brain barrier integrity, inflammation and thrombin induced injury. However, results regarding functional outcome are conflicting. Little data is available on the effect of TTM after spontaneous ICH in humans. Single-center observational studies have shown reduced perihematomal edema under mild hypothermia and an association with favorable outcome. However, these beneficial effects on mortality and functional outcome have not been confirmed in randomized studies so far. Thus, results from ongoing, prospective randomized controlled trials are highly anticipated. PMID- 27397066 TI - Therapeutic Drugs in Bone Loss-Associated Disorders: Clinical Outcomes and Challenges. AB - Current therapeutic drugs for the treatment of bone loss-associated disorders such as osteoporosis and metastatic bone disease have limited clinical outcomes, namely in terms of efficiency and sustainability. Given the ageing of population in developed countries and the cumulative costs with treatment, bone loss associated disorders represent a major socioeconomic burden worldwide. In this review, the therapeutic agents targeting bone loss tested in clinical and pre clinical trials are summarized, as well as the challenges encountered by clinicians and patients. In an effort to attain costeffective clinical outcomes, potential cellular and signalling targets are disclosed. PMID- 27397067 TI - Graphene: A Comprehensive Review. AB - Graphene, a one-atom thick, two-dimensional sheets of sp2hybridized carbon atoms packed in a hexagonal lattice with a Caron-Carbon distance of about 0.142 nm. Its extended honeycomb network forms the basic building block of other important allotropes; it can be stacked to form 3-Dgraphite, rolled to form 1-D-nanotubes and wrapped to form 0-D-fullerenes. Long-range pi conjugation in graphene results in its extraordinary thermal, mechanical and electrical properties, which have been the interest of many theoretical studies and recently became an exciting area for scientists. Graphene is impermeable to gas and liquids, has excellent thermal conductivity and higher current density in comparison to other most effective materials. All of its exceptional properties have opened up new avenues for the use of graphene in nano-devices and nano-systems, which initiated its prominent use as a material for drug targeting. In addition, several fabrication techniques are outlined, starting from the mechanical exfoliation of high-quality graphene to the direct growth on silicon carbide or metal substrates and from the chemical routes utilizing graphene oxide to the newly developed approach at the molecular level. By this article reviewers intend to emphasize on unique properties, fabrication techniques and updated applications of graphene. In addition, we discuss about the potential of graphene in drug targeting in fields of nanotechnology, biomedical engineering and technology and its use for innovations in various fields such as electronics and photonics. PMID- 27397068 TI - Inflammasome as a Key Pathogenic Mechanism in Endometriosis. AB - BACKGROUND: Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved. OBJECTIVES: Revise new inflammatory pathogenic mechanisms involved in endometriosis, namely inflammasome. METHOD: Literature review for the updating of data to give new clues for different options of treatments. RESULTS: Inflammasome has been described as a multiprotein complex and is considered a key regulator of the innate and adaptive host response that surveys the cytosol and other compartments into the cell. It is involved in the immediate detection and responds to the presence of danger- and pathogen-associated molecular patterns named DAMPs and PAMPs respectively, and has been described in several cells, mainly on immune cells of the myeloid lineage and epithelial cells in tissues with mucosal surfaces. Four inflammasome are formed in a stimulus-dependent manner of distinct composition. They are the Noll Like Receptors (NLR) proteins Nlrp1b, Nlrp3, Nlrc4, and Nlrp6, as well as the absent in melanoma 2 (AIM2). They activate the production of IL-1beta and IL-18 that induce a host response such as pyroptosis, a proinflammatory cell death and the secretion of leaderless cytokines and growth factors. Inflammasome is linked to atherosclerosis, periodic fever syndromes, vitiligo, Crohn's disease, gout, asbestosis, silicosis, Alzheimer's disease and periodontitis. Endometriosis has been related with IL 1beta and Another NLR, Nlrp7, was correlated with myometrial invasion in human endometrial cancer tissue. CONCLUSIONS: These new clues regarding the pathogenic mechanisms involving the inflammasome may be crucial in the future development for endometriosis therapy. PMID- 27397069 TI - Hereditary angioedema presenting as compartment syndrome in a white girl. PMID- 27397071 TI - Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain - In vivo and in vitro evidence. AB - The repeated administration of microglial inhibitor (minocycline) and CCR2 antagonist (RS504393) attenuated the neuropathic pain symptoms in rats following chronic constriction injury of the sciatic nerve, which was associated with decreased spinal microglia activation and the protein level of CCL2 and CCR2. Furthermore, in microglia primary cell cultures minocycline downregulated both CCL2 and CCR2 protein levels after lipopolysaccharide-stimulation. Additionally, in astroglia primary cell cultures minocycline decreased the expression of CCL2, but not CCR2. Our results provide new evidence that modulation of CCL2/CCR2 pathway by microglial inhibitor as well as CCR2 antagonist is effective for neuropathic pain development in rats. PMID- 27397072 TI - Alpha-mangostin attenuates brain inflammation induced by peripheral lipopolysaccharide administration in C57BL/6J mice. AB - Neuroinflammation is an important feature in the pathogenesis and progression of neurodegenerative diseases. Molecules with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated that alpha-mangostin (alpha-MG), a natural xanthone purified from mangosteen pericarp, reduced brain levels of pro-inflammatory cytokine interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and 18 kDa translocator protein (TSPO) in an animal model of peripheral LPS-induced neuroinflammation. We think that evaluation of alpha-MG as an adjuvant treatment in preclinical models of AD, PD, multiple sclerosis and other diseases with known shared pathology merits further consideration. PMID- 27397070 TI - T cell cytokine signatures: Biomarkers in pediatric multiple sclerosis. AB - Although multiple sclerosis is predominantly regarded as a disease of young adulthood, up to 5% of MS patients are diagnosed prior to age eighteen. The predominant form of MS is relapsing-remitting characterized by exacerbations of symptoms followed by periods of remission. The majority of disease modifying drugs target T cell proliferation or block migration into the central nervous system. Although these treatments reduce relapses, disease progression still occurs, warranting therapeutic strategies that protect the CNS. Biomarkers to indicate relapses would facilitate a personalized approach for add-on therapies that protect the CNS. A multiplex cytokine bead array was performed to detect T cell associated cytokines in sera from patients 6-20years of age with pediatric onset MS clinically diagnosed in relapse or remission compared to healthy control patients. Of the 25 cytokines evaluated, 17 were increased in patients clinically diagnosed in relapse compared to sera from control patients in contrast to only 9 cytokines in the clinically diagnosed remission group. Furthermore, a linear regression analysis of cytokine levels in the remission population showed 12 cytokines to be statistically elevated as a function of disease duration, with no effect observed in the relapse population. To further explore this concept, we used a multivariable stepwise discriminate analysis and found that the following four cytokines (IL-10, IL-21, IL-23, and IL-27) are not only a significant predictor for MS, but have important predictive value in determining a relapse. Since IL-10 and IL-27 are considered anti-inflammatory and IL-21 and IL-23 are pro-inflammatory, ratios of these cytokines were evaluated using a Duncan's multiple range test. Of the six possible combinations, increased ratios of IL 10:IL-21, IL-10:IL-23, and IL-10:IL-27 were significant suggesting levels of IL 10 to be a driving force in predicting a relapse. PMID- 27397073 TI - RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats. AB - Major histocompatibility complex class l (MHC I) molecules play a role in determining whether transplanted cells will be accepted or rejected, and masking of MHC I on donor cells has been found useful for immunoprotection of neural xenografts. In the present study, primary human embryonic lung fibroblasts (HELF), HELF treated with lentivirus-mediated small interfering RNAs (siRNAs) targeting human leukocyte antigen A2 (HLA A2, MHC I in humans) (siHELF), and rat embryonic lung fibroblasts (RELF) were stereotaxically grafted into the striatum of 6-hydroxydopamine lesioned rats to explore whether knockdown of HLA A2 could reduce host immune responses against xenografts. Before lentiviral infection, the cells were transduced with retroviruses harboring tyrosine hydroxylase cDNA. Knockdown of HLA A2 protein was examined by Western blotting. The immune responses (the number of CD4 and CD8 T-cells in the brain and peripheral blood), glial reaction, and survival of human fibroblasts were quantitatively evaluated by flow cytometry and immunohistochemistry at 4d, 2w, and 6w post-graft. Animal behaviors were assessed by counting apomorphine-induced rotations pre- and post grafts. It was shown that a lower level of HLA A2 was observed in siHELF grafts than in HELF grafts, and knockdown of HLA A2 decreased rat immune responses, as indicated by less remarkable increases in the number of CD8 and CD4 T-cells in the brain and the ratio of CD4:CD8 T-cells in the peripheral blood in rats grafted with siHELF. Rats grafted with siHELF exhibited a significant improvement in motor asymmetry post-transplantation and a better survival of human fibroblasts at 2w. The increasing number of activated microglia and the decreasing number of astrocytes were found in three groups of rats post implantation. These data suggested that RNAi-mediated knockdown of HLA A2 could suppress acute rejection against xenogeneic human cell transplants in the rat brain. PMID- 27397074 TI - Impaired regulatory B cells in myasthenia gravis. AB - Regulatory B cells (Bregs) attenuate the severity of experimental autoimmune myasthenia gravis (EAMG) in an interleukin-10 (IL-10)-dependent manner. The goal of this study was to investigate the role of human Bregs in MG focusing on CD19(+)CD1d(hi) CD5(+) and CD19(+)CD24(hi)CD38(hi) subsets. We found that MG patients exhibited a decrease in the frequency of both Breg subsets and IL-10 producing B cells within each subset, which correlated with disease severity. In addition, there was impaired suppression of Th1 polarization in MG. These findings, taken together with EAMG data, indicate that Bregs play an important role in regulating the severity of MG. PMID- 27397075 TI - Effect of Chlorovirus ATCV-1 infection on behavior of C57Bl/6 mice. AB - Neuroinflammation induced during immune responses to viral infections in the brain affect behavior. Unexpected evidence that oral gavage of an algal virus in its host algal cells could alter cognition was further examined by directly injecting purified algal virus ATCV-1 intracranially into C57BL/6 mice. After 4weeks, the ATCV-1 infection impaired delayed location recognition memory, and also reduced and anxiety. Corresponding to these effects, heightened ATCV-1, IL 6, iNOS, IFN-gamma, and CD11b expression in brains was observed 3-days and/or 8 weeks post infection compared with control mice. These results imply that ATCV-1 infection damages the hippocampus via induction of inflammatory factors. PMID- 27397077 TI - BAFF is decreased in the cerebrospinal fluid of multiple sclerosis at clinical onset. AB - B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset. Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, QBAFF) and Index (QBAFF/QAlb, BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (p<0.05). BAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (p<0.01). A significant inverse correlation between QIgG and QBAFF (r: -0.4, p<0.05) and between BAFF index and IgGIF (r: -0.4, p<0.05) or IgG Index (r: -0.4, p=0.05) was found in IgGOB+. The decreased CSF levels of BAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. PMID- 27397076 TI - Fine specificity of the antibody response to Epstein-Barr nuclear antigen-2 and other Epstein-Barr virus proteins in patients with clinically isolated syndrome: A peptide microarray-based case-control study. AB - We analyzed the fine specificity of antibodies to Epstein-Barr nuclear antigen-2 (EBNA-2) and other Epstein-Barr virus (EBV) proteins in 29 patients with clinically isolated syndrome (CIS, the first clinical manifestation of multiple sclerosis [MS]) and 29 controls with a peptide microarray containing 117 overlapping peptides representing the full-length EBNA-2 protein and 71 peptides from 8 further EBV proteins. While EBV peptide antibodies were elevated in CIS, suggesting that EBV contributes to MS early during disease development, they discriminated groups only slightly better than EBNA-1 antibodies. Thus, the additional value of EBV peptide antibodies as diagnostic biomarkers for CIS appears moderate. PMID- 27397079 TI - Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome. AB - BACKGROUND: Activation of Toll-like receptor 4 (TLR4) contributes to brain injury and poor outcome after cerebral ischemia. The expression of this receptor on monocytes is increased in patients with acute ischemic stroke. Endotoxin is an endogenous ligand for TLR4. The aim of our study was to determine if plasma endotoxin activity is increased in stroke patients and correlates with functional outcome. METHODS: We included 88 patients with ischemic stroke (median age: 71, 56.8% men) and 59 age-matched controls. Plasma endotoxin activity and level of proteins regulating endotoxin interaction with TLR4 (LPS binding protein - LBP and sCD14) were measured in blood samples taken at day 1 (within 24h after stroke symptoms onset), 3 and 6. Short-term functional outcome was assessed at day 14 using modified Rankin Scale. Unfavourable outcome was defined as modified Rankin Scale score>2. RESULTS: Compared to controls, stroke patients had higher plasma endotoxin activity on day 1 (median: 0.39 vs 0.32EU/mL, P=0.03) as well as higher LBP (median: 18.7 vs 11.5MUg/mL, P<0.01) and sCD14 level (median: 1330 vs 1070ng/mL, P<0.01). Plasma LPS activity and levels of LBP and sCD14 significantly rose during stroke. Higher LPS activity measured on day 6 was associated with unfavourable outcome (OR: 3.94, 95%CI: 1.03-15.02, P=0.04, adjusted for age and stroke severity). CONCLUSIONS: Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome. PMID- 27397080 TI - Transcriptional expression of inflammatory mediators in various somatosensory relay centers in the brain of rat models of peripheral mononeuropathy and local inflammation. AB - Contradictory results have been reported regarding the role of inflammatory mediators in the central nervous system in mediating neuropathic pain and inflammatory hyperalgesia following peripheral nerve injury or localized inflammation. The present study aims to correlate between the mRNA expression and protein secretion of proinflammatory cytokines and nerve growth factor (NGF), in the dorsal root ganglia (DRGs), spinal cord, brainstem and thalamus, and pain related behavior in animal models of peripheral mononeuropathy and localized inflammation. Different groups of rats (n=8, each) were subjected to either lesion of the nerves of their hindpaws to induce mononeuropathy or intraplantar injection of endotoxin (ET) and were sacrificed at various time intervals. TNF alpha, IL-1beta and NGF mRNA expression and protein levels in the various centers involved in processing nociceptive information were determined, by RT-PCR and ELISA. Control groups were either subjected to sham surgery or to saline injection. Mononeuropathy and ET injection produced significant and sustained increases in the mRNA expression and protein levels of TNF-alpha, IL-1beta and NGF in the ipsilateral and contralateral DRGs, spinal cord, and brainstem. No significant and consistent changes in the mRNA expression of cytokines were noticed in the thalamus, while a downregulation of the NGF-mRNA level was observed. The temporal and spatial patterns of the observed changes in mRNA expression of cytokines and NGF are not closely in phase with the observed allodynia and hyperalgesia in the different models, suggesting that the role of these mediators may not be reduced exclusively to the production and maintenance of pain. PMID- 27397081 TI - Family-based association study of interleukin 10 (IL10) and interleukin 10 receptor alpha (IL10RA) functional polymorphisms in schizophrenia in Polish population. AB - Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. Interleukin-10 (IL10) and it's receptor IL10RA may play an important role for immunological aspects in etiologies of major psychiatric disorders including schizophrenia. The aim of this study was to perform a transmission disequilibrium test (TDT) on a group of 146 schizophrenia trios from the Polish population. Functional polymorphisms from IL10 (rs1800872, rs1800871, rs1800896, rs1800890, and rs6676671) and IL10RA (rs3135932 and rs2229113) genes were analyzed. A lack of association with schizophrenia was detected for IL10 and IL10RA single polymorphisms and haplotypes. PMID- 27397078 TI - Calcitonin gene-related peptide contributes to peripheral nerve injury-induced mechanical hypersensitivity through CCL5 and p38 pathways. AB - The role of calcitonin gene related peptide (CGRP) in neuropathic pain was investigated in a mouse model of neuropathic pain, spinal nerve L5 transection (L5Tx). Intrathecal injection (i.t.) of CGRP8-37, a CGRP antagonist, significantly reduced L5Tx-induced mechanical hypersensitivity and lumbar spinal cord CCL5 expression. i.t. injection of a CCL5 neutralizing antibody significantly inhibited L5Tx-induced mechanical hypersensitivity. Further, pre treatment with a p38-inhibitor, SB203580, was able to reduce CGRP-induced mechanical hypersensitivity, but not CGRP-induced CCL5 production. Our data indicate that CGRP can play its pro-nociceptive role through both a spinal cord CCL5-dependent, p38-independent pathway, and a p38-depenented, CCL5-independent pathway. PMID- 27397082 TI - Immunoproteomic studies on paediatric opsoclonus-myoclonus associated with neuroblastoma. AB - We aimed to identify new cell-membrane antigens implicated in opsoclonus myoclonus with neuroblastoma. The sera of 3 out of 14 patients showed IgG electron-microscopy immunogold reactivity on SH-SY5Y neuroblastoma cells. Immunoprecipitation experiments using rat brain synaptosomes and SH-SY5Y cells led to the identification of: (1) thirty-one nuclear/cytoplasmic proteins (including antigens HuB, HuC); (2) seven neuronal membrane proteins, including the Shaw-potassium channel Kv3.3 (KCNC3), whose genetic disruption in mice causes ataxia and generalized muscle twitching. Although cell-based assays did not demonstrate direct antigenicity, our findings point to Shaw-related subfamily of the potassium voltage-gated channels complexed proteins as hypothetical antigenic targets. PMID- 27397083 TI - Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats. AB - The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and beta2- and alpha1-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average beta2- and alpha1-AR thymocyte surface density changed in the opposite direction with age; the density of beta2-AR decreased, whereas that of alpha1-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of beta2-ARs, but it increased that of alpha1-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age- and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic regulatory network in adult rats. PMID- 27397084 TI - General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation. AB - Relapsing-remitting multiple sclerosis (MS)(2) is characterized by phases of acute neuroinflammation followed by spontaneous remission. Termination of inflammation is accompanied by an influx of regulatory T cells (Tregs).(3) The molecular mechanisms responsible for directing Tregs into the inflamed CNS tissue, however, are incompletely understood. In an MS mouse model we show that the stress kinase general control non-derepressible 2 (GCN2),(4) expressed in T cells, contributes to the resolution of autoimmune neuroinflammation. Failure to recover from acute inflammation was associated with reduced frequencies of CNS infiltrating Tregs. GCN2 deficient Tregs displayed impaired migration to a CCL2 gradient. These data suggest an important contribution of the T cell stress response to the resolution of autoimmune neuroinflammation. PMID- 27397085 TI - The association of serum 25-hydroxyvitamin D levels with multiple sclerosis severity and progression in a case-control study from China. AB - OBJECTIVE: Low vitamin D levels had been shown to play a role in the pathogenesis of multiple sclerosis (MS). Currently, there is little information regarding the correlation between levels of vitamin D and MS in Chinese. This study aimed at detection of association between serum 25-hydroxyvitamin D [25(OH) D] concentrations and MS and its relation to the disease severity in Chinese. METHODS: The present study was a case-control type, it included 141 patients with definitive MS on the basis of 'McDonald' criteria and 282 age-sex matched controls. All patients were clinically evaluated including disease severity using expanded disability status scale (EDSS) score and progression index (PI). Serum 25(OH) D measurements were performed at baseline. RESULTS: The median serum level of 25(OH) D in patients with MS was 15.9 (IQR, 11.4-24.4) ng/mL, which was significantly lower (P<0.0001) than those in healthy controls (20.6 [IQR, 15.3 27.7] ng/mL). There was a negative correlation between levels of 25(OH) D and the EDSS score (r=-0.549, P<0.0001). In multivariate conditional logistic analyses using dichotomous 25(OH) D levels, values less than or equal to 20ng/mL indicted higher risk of MS (OR 1.691, 95 CI: 1.058-2.394; P=0.024). Similarly, in binary logistic multivariate analyses using dichotomous 25(OH) D levels, values less than or equal to 20ng/mL indicted the MS high progression (OR 6.278, 95 CI: 2.662 15.659; P<0.001). CONCLUSION: Low serum 25(OH) D levels were associated with increased activity and progression in Chinese patients with MS. Further analytical work is required to establish a causal association between vitamin D status and MS risk and progression. PMID- 27397086 TI - Exploring the role of inflammation in the malignant transformation of low-grade gliomas. AB - Studies of inflammatory mediators have established the tumor micro-environment as a driver of oncogenesis. This inflammatory milieu often precedes cancer, however recent data also point to the ability of oncogenic changes to induce inflammatory responses that are later harnessed by the tumor to survive and proliferate. In this review, we propose that the IDH1 mutation, present in the majority of low grade gliomas (LGGs), initiates an inflammatory cascade that is ultimately hijacked by the tumor. Glioma infiltrating macrophages and microglia (GIMs) are polarized to the M2 phenotype, subverting the host's adaptive immune response, and fostering a tumor milieu ripe for angiogenesis, migration, and metastasis. As data continue to expand the role of inflammation in low-grade gliomas, new molecular pathways may emerge as therapeutic targets that offer a window of opportunity to intervene before the malignant transformation (MT) of LGGs occurs. PMID- 27397087 TI - Distinct intrathecal interleukin-17/interleukin-6 activation in anti-N-methyl-d aspartate receptor encephalitis. AB - The aim of this study was to compare serum and cerebrospinal fluid (CSF) cytokine/chemokine levels between anti-NMDAR and anti-LGI1 encephalitis patients. Samples from fourteen anti-NMDAR encephalitis patients, ten anti-LGI1 encephalitis patients, and ten controls were analyzed for the following cytokines/chemokines: IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17A, IL-23, GM-CSF, IFN-gamma, TNF-alpha, and CXCL13. Compared with controls, CSF IL 17A, IL-6 and CXCL13 were elevated in anti-NMDAR encephalitis patients (post-hoc p-values 0.002, 0.011, and 0.011, respectively) but not in anti-LGI1 encephalitis patients. In the serum, only IL-2 was increased in anti-NMDAR encephalitis. Intrathecal IL-17/IL-6 activation is a characteristic of anti-NMDAR encephalitis. PMID- 27397089 TI - FDG-PET hyperactivity pattern in anti-NMDAr encephalitis. AB - FDG-PET can show anteroposterior glucose metabolism gradient in anti-NMDAr encephalitis, but there are also suggestions that basal ganglia are involved. We examined FDG-PET scans in 5 consecutive episodes of serologically proven anti NMDAr encephalitis, compared with healthy controls. We confirmed the anteroposterior metabolic gradient and found a significant FDG uptake increase in the caudate nuclei in episodes of varying intensity and delay from the onset of the symptoms. FDG-PET can be useful in the work-up of suspected anti-NMDAr encephalitis disclosing a characteristic cortical and sub-cortical metabolism pattern. PMID- 27397088 TI - Synergetic and antagonistic effects of combined calcitriol and interferon-beta treatment on cytokine production by stimulated PBMCs. AB - BACKGROUND: We evaluated the effects of calcitriol and interferon-beta on in vitro PBMC cytokine production from a cohort of 22 healthy adults not on medication. METHODS: PBMCs were incubated with calcitriol and/or 100 or 400IU interferon-beta or nothing, followed by stimulation with concanavalin A. RESULTS: When combined, calcitriol and interferon-beta appeared to potentiate the effects of one another on reducing IL-6. Calcitriol significantly reduced the production of IL-2, IL-4, IL-6, and IFN-gamma, while interferon-beta significantly reduced production of IL-6 and TNF-alpha, and increased IL-10. DISCUSSION: This is the first study to evaluate the effects of combined calcitriol and interferon-beta on cytokine production in PBMCs in vitro, demonstrating novel synergetic effects. PMID- 27397091 TI - Polymorphism in Endothelin-1 Gene: An Overview. AB - Endothelin-1, (ET-1, EDN1) is an endogenous polypeptide which demonstrates dominant vasoconstriction activity and mitogenic effect. It has positive inotropic and chronotropic effects on the heart, stimulates the sympathetic and the renin-angiotensin-aldosterone systems and modifies homeostasis. The human ET 1 gene which consists of 6836 nucleotides located on chromosome 6p23-p24 produces Pre-pro-ET-1, which is consequently cleaved to big-ET-1. The mature 21-amino acid ET-1 is generated by subsequent enzymatic cleavage of the big-ET-1. A comprehensive review of the literature on the consequences of different ET-1 gene variants on ET-1 linked diseases has not been accomplished. Many variants of ET-1 gene, including transversion, transition, insertion, and repeated nucleotide polymorphisms, which influence the hereditary risk of cardiovascular and other related diseases have already been located, genotyped, and examined. Among them ten polymorphisms including transversion; -1370 (T-1370G) (rs1800541), +5665 (Lys198Asn) (rs5370), G2288T polymorphisms (rs2070699), and -974 C=5 mm or other; anterior movement or other; and impaction asymmetry or other). There were no significant differences in the nasal septum angle and the airway of all patients. Among the patient groups, there were no significant differences in the nasal septum angle and airway. We concluded that conventional LI osteotomy did not influence the nasal septum deviation or the left and right airway asymmetry. Differences in the method of moving the maxilla have not been shown to affect changes in the nasal septum. PMID- 27397094 TI - Haemophilia registries to complement clinical trial data: a pious hope or an urgent necessity?: Reflections on a possible way forward. PMID- 27397095 TI - Association of Comorbidity, Age, and Radical Surgical Therapy for Prostate Cancer, Bladder Cancer, and Renal Cell Carcinoma. AB - OBJECTIVE: To assess trends and factors driving aggressive surgery for patients >75 years diagnosed with prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC). METHODS: We identified all patients >75 years diagnosed with PCa, BCa, and RCC from the Surveillance, Epidemiology and End Results Medicare registry during 1992-2009. We analyzed the comorbidity and trends in radical cystectomy (RC), nephrectomy, and radical prostatectomy (RP) for these cohorts. Predictive factors for receiving aggressive surgery were assessed using logistic regression analysis. RESULTS: We identified cohorts of 85,073 PCa, 44,801 BCa, and 10,737 RCC patients. Among the BCa patients, 5.75% underwent RC and 78.2% had a Charlson comorbidity score (CCS) of <=1. The trend of RC did not change significantly. There was a significant change in receipt of RP (P = .01). There were 85.8% of PCa patients who had a CCS <=1 and 2.67% underwent RP. Approximately 65.2% of RCC patients had nephrectomy whereas 76.2% had CCS of <=1. There was a decline in receipt of nephrectomies (P < .0001). Younger age, high stage or grade disease, and lower comorbidity were associated with higher odds of receiving RC, RP, and nephrectomy. CONCLUSION: In addition to stage and grade, age remains an important factor influencing the decision to undergo curative surgical therapy for PCa, BCa, and RCC patients >75 years. Comorbidity is also predictive, but to a lesser extent. PMID- 27397096 TI - Comparison of Nephroscope-assisted "Pulling Thread" Technique and Conventional Open Placement of Peritoneal Dialysis Catheters in Patients With End-stage Renal Disease. AB - OBJECTIVE: To compare the clinical outcomes between nephroscope-assisted "pulling thread" technique (NPT) and conventional open placement (OP) of catheters in peritoneal dialysis patients. MATERIALS AND METHODS: We retrospectively reviewed 97 consecutive patients undergoing either NPT (n = 57) or OP (n = 40) for peritoneal dialysis catheter placement from March 2007 to May 2015. The operation related data, early catheter-related complications, and long-term catheter survival were analyzed. RESULTS: The overall early catheter-related complication rate was lower in NPT compared with OP (P = .0035). Furthermore, OP had a significantly higher rate of catheter migration than NPT (15.0% vs 3.5%, respectively, P = .042). Patients undergoing NPT had better catheter survival than those undergoing OP, with 1-year survival rates of 93.5% and 81.1%, and 2 year survival rates of 83.0% and 63.3%, respectively (P = .007). CONCLUSION: NPT exhibited superiority to OP in terms of the postoperative early complication rate and catheter survival. This novel technique would thus be ideal for peritoneal dialysis catheter placement. PMID- 27397097 TI - Outcomes and Complications of Robotic-assisted Laparoscopic Prostatectomy in a Community Hospital Setting. AB - OBJECTIVE: To evaluate outcomes for 144 robotic-assisted laparoscopic prostatectomies (RALPs) conducted upon introduction of a robotic surgery program in a community hospital. METHODS: Patient data were reviewed for 144 patients who underwent RALP from January 2013 to February 2015. Complications and oncologic and functional outcomes were assessed. Student t test and analysis of variance were used to compare differences among study groups. RESULTS: Median age was 64 (IQR 60-68) and median prostate-specific antigen was 5.61 (interquartile range [IQR] 4.3-7.7). Stage pT2, pT3a, and 3b pathology was present at rates of 77%, 21%, and 8%, respectively. Median operative blood loss was 200 mL (IQR 150-300), median operative time was 1.75 hours (IQR 1.5-2.3), and median length of stay was 2 days (IQR 1-2). Overall, there were 9 complications (6.8%); 2 were classified as major and 7 as minor events. The overall positive surgical margin rate was 19%, with positive surgical margin rates of 11% and 46.8% in patients with pT2 and pT3 disease, respectively (P < .001). The overall biochemical recurrence rate at 12 months was 12.5% occurring in 10% and 20% of patients with pT2 and pT3 disease, respectively (P = .32). Continence success at 1, 6, and 12 months was 67%, 90%, and 93%, respectively. Potency success in men with normal to mild erectile dysfunction at baseline was 76% and 83% at 6 and 12 months, respectively. CONCLUSION: RALP in this community hospital practice was both safe and effective. Complication rates and oncologic and functional outcomes in this study were commensurate with those reported by high volume centers. PMID- 27397098 TI - Surveillance of Small Renal Masses. AB - The widespread utilization of imaging has led to an increasing incidence of small renal masses (SRMs). However, at least 20% are benign. Nevertheless, nephron sparing surgery is the standard treatment for SRMs without pretreatment characterization with biopsy. Elderly patients and patients with multiple comorbidities and limited life expectancy may safely be managed with active surveillance with low risk of disease progression and mortality. An initial period of observation to determine tumor growth kinetics is safe and appropriate in select candidates. Renal tumor biopsy is accurate, safe and should be considered for SRMs prior to finalizing treatment plans. PMID- 27397099 TI - Proximally Directed Double-looped Epididymis and Vas Deferens Simulating Vas Duplication: The Importance of Precise Definition of Abnormal Ductal Anatomy in Cryptorchidism. AB - OBJECTIVE: Epididymal and vasal abnormalities are frequently recognized with undescended testes. The most common defect identified is the extended or elongated epididymis, an anomaly in which the epididymal tail extends distally beyond the testis before looping back upon itself, then following its normal course. Although the impact on fertility has not been established, the necessity of recognizing these vaso-epididymal abnormalities surgically is obvious as these frequently simulate a blind-ending spermatic cord leading to inadvertent excision or leaving the unseen testis more proximally in the abdomen. With this in mind, we describe a more complex vaso-epididymal structural abnormality with proximal extension of the epididymis and vas simulating duplication of these structures. METHODS: The varied surgical findings of a proximally directed double-looped abnormal epididymis and vas deferens associated with cryptorchid testes were identified in 15 children. In all instances, the epididymis extended proximally up the spermatic cord for at least 4 cm, simulating reduplication of the vas deferens and leading to bizarre ductal anatomy and confusing anatomical findings. RESULTS: In our practice, a number of abnormalities of the vaso-epididymal structures have been defined, but we isolated a number of situations in which identification of a proximally directed double-looped epididymis was noted during surgical exploration for cryptorchidism. Our review demonstrated several situations such as this where misidentification could have resulted in inadvertent transection of the vas deferens. CONCLUSION: The need for recognition of these unusual ductal abnormalities associated with cryptorchid testes is re emphasized by these extreme examples to prevent surgical mishaps at orchidopexy. PMID- 27397101 TI - Development of infectious clones of a wild-type Korean rabies virus and evaluation of their pathogenic potential. AB - Most reverse genetic (RG) systems for rabies viruses (RVs) have been constructed on the genome background of laboratory-adapted strains. In this study, we developed an RG system using a Korean wild type (KGH) strain to investigate the pathogenic potential of different strains. We developed a RG system with the KGH strain for the first time. Following the complete genome sequencing of the KGH strain, pKGH infectious clones were constructed using the CMV/T7 promoter, and HamRz and HdvRz were introduced to allow self-cleavage of the synthesized RNA. We successfully recovered the rescued virus by constructing chimeric RVs in which we replaced a part of the construct with the partial gene from the fixed RC-HL strain. The rescued viruses formed clearer and countable plaques in an immunostaining plaque assay, with a distinct plaque morphology. Furthermore, compared with the chimeric RVs, the pKGH/RCinsDelta4 strain containing the KGH strain G protein exhibited a decreased efficiency of cell-to-cell spreading in BHK-21 cells and significantly reduced (100-1000 fold) replication kinetics. However, pKGH/RCinsDelta4 strain-infected mice revealed 100% morbidity at 11days post-infection, whereas other chimeric RV strains showed no mortality. Our RG system is a useful tool for studying differences in the cell-to-cell spreading efficiency and replication with respect to the different internalization patterns of street and fixed laboratory-adapted viruses. PMID- 27397100 TI - Virulence factors in porcine coronaviruses and vaccine design. AB - Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis. PMID- 27397103 TI - CDH11 inhibits proliferation and invasion in head and neck cancer. AB - BACKGROUND: In this study, we use a bioinformatics-based strategy to nominate a tumor suppressor gene cadherin-11 (CDH11) and investigate its role in growth and invasion in head and neck squamous cell carcinoma (HNSCC). METHODS: Using the OncomineTM database to compare HNSCC and normal specimens, CDH11 was nominated as having a role in HNSCC. CDH11 expression in HNSCC was evaluated by immunohistochemistry on a tissue microarray (TMA) and immunoblotting and immunofluorescence of cell lines. The functional impact of CDH11 on proliferation and invasion was evaluated after siRNA-mediated knockdown. RESULTS: In silico analysis suggested that CDH11 is overexpressed in HNSCC compared to normal specimens. HNSCC TMA exhibited a small but significant increase in intensity and proportion of CDH11. By immunoblot analysis, CDH11 was higher in 4/7 HNSCC cell lines compared to normal keratinocytes; CDH11 was highly upregulated in UM-SCC-47 and UM-SCC-74A and detectable in UM-SCC-14A and UM-SCC-29 cell lines. Downregulation of CDH11 in both UM-SCC-29 and UM-SCC-47 using two different siRNAs enhanced proliferation and invasion. CONCLUSION: CDH11 inhibits cell proliferation and invasion of HNSCC. This suggests that CDH11 functions as a tumor suppressor gene in head and neck cancer. Our findings emphasize the importance of verifying in silico findings with functional studies. PMID- 27397102 TI - Long Non-coding RNAs and Their Roles in Non-small-cell Lung Cancer. AB - As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Lung cancer is characterized by genomic and epigenomic alterations; however, mechanisms underlying lung tumorigenesis remain to be elucidated. Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs that consist of ?200 nucleotides but possess low or no protein-coding potential. Accumulating evidence indicates that abnormal expression of lncRNAs is associated with tumorigenesis of various cancers, including lung cancer, through multiple biological mechanisms involving epigenetic, transcriptional, and post-transcriptional alterations. In this review, we highlight the expression and roles of lncRNAs in NSCLC and discuss their potential clinical applications as diagnostic or prognostic biomarkers, as well as therapeutic targets. PMID- 27397104 TI - A glucuronoyl esterase from Acremonium alcalophilum cleaves native lignin carbohydrate ester bonds. AB - The Glucuronoyl esterases (GE) have been proposed to target lignin-carbohydrate (LC) ester bonds between lignin moieties and glucuronic acid side groups of xylan, but to date, no direct observations of enzymatic cleavage on native LC ester bonds have been demonstrated. In the present investigation, LCC fractions from spruce and birch were treated with a recombinantly produced GE originating from Acremonium alcalophilum (AaGE1). A combination of size exclusion chromatography and (31) P NMR analyses of phosphitylated LCC samples, before and after AaGE1 treatment provided the first evidence for cleavage of the LC ester linkages existing in wood. PMID- 27397105 TI - MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer. AB - Nucleotide variants in microRNA regions have been associated with disease; nevertheless, few studies still have addressed the allele-dependent effect of these changes. We studied microRNA genetic variation in human populations and found that while low-frequency variants accumulate indistinctly in microRNA regions, the mature and seed regions tend to be depleted of high-frequency variants, probably as a result of purifying selection. Comparison of pairwise population fixation indexes among regions showed that the seed had higher population fixation indexes than the other regions, suggesting the existence of local adaptation in the seed region. We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B). We found differences in the expression between alleles and in the regulation of several genes involved in cancer, such as TP53, KIT, CDH1, CLH, and TERT, which may result in changes in regulatory networks related to tumorigenesis. Furthermore, luciferase-based assays showed that MIR499A could be regulating the cadherin CDH1 and the cell adhesion molecule CLH1 in an allele-dependent fashion. A better understanding of the effect of microRNA variants associated with disease could be key in our way to a more personalized medicine. PMID- 27397107 TI - Early thymectomy leads to premature immunologic ageing: An 18-year follow-up. PMID- 27397106 TI - A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding. AB - Persistent neurotoxic side effects of oxaliplatin (OX) chemotherapy, including sensory ataxia, limit the efficacy of treatment and significantly diminish patient quality of life. The common explanation for neurotoxicity is neuropathy, however the degree of neuropathy varies greatly among patients and appears insufficient in some cases to fully account for disability. We recently identified an additional mechanism that might contribute to sensory ataxia following OX treatment. In the present study, we tested whether that mechanism, selective modification of sensory signaling by muscle proprioceptors might result in behavioral deficits in rats. OX was administered once per week for seven weeks (cumulative dose i.p. 70mg/kg) to adult female Wistar rats. Throughout and for three weeks following treatment, behavioral analysis was performed daily on OX and sham control rats. Compared to controls, OX rats demonstrated errors in placing their hind feet securely and/or correctly during a horizontal ladder rung task. These behavioral deficits occurred together with modification of proprioceptor signaling that eliminated sensory encoding of static muscle position while having little effect on encoding of dynamic changes in muscle length. Selective inability to sustain repetitive firing in response to static muscle stretch led us to hypothesize that OX treatment impairs specific ionic currents, possibly the persistent inward Na currents (NaPIC) that are known to support repetitive firing during static stimulation in several neuron types, including the class of large diameter dorsal root ganglion cells that includes muscle proprioceptors. We tested this hypothesis by determining whether the chronic effects of OX on the firing behavior of muscle proprioceptors in vivo were mimicked by acute injection of NaPIC antagonists. Both riluzole and phenytoin, each having multiple drug actions but having only antagonist action on NaPIC in common, reproduced selective modification of proprioceptor signaling observed in OX rats. Taken together, these findings lead us to propose that OX chemotherapy contributes to movement disability by modifying sensory encoding, possibly via a chronic neurotoxic effect on NaPIC in the sensory terminals of muscle proprioceptors. PMID- 27397108 TI - Addition of sodium criterion to SOAR stroke score. AB - OBJECTIVES: To examine the usefulness of including sodium (Na) levels as a criterion to the SOAR stroke score in predicting inpatient and 7-day mortality in stroke. MATERIALS AND METHODS: Data from the Norfolk and Norwich University Hospital Stroke & TIA register (2003-2015) were analysed. Univariate and then multivariate models controlling for SOAR variables were used to assess the association between admission sodium levels and inpatient and 7-day mortality. The prognostic ability of the SOAR and SOAR Na scores for mortality outcomes at both time points were then compared using the Area Under the Curve (AUC) values from the Receiver Operating Characteristic curves. RESULTS: A total of 8493 cases were included (male=47.4%, mean (SD) 77.7 (11.6) years). Compared with normonatremia (135-145 mmol/L), hypernatraemia (>145 mmol/L) was associated with inpatient mortality and moderate (125-129 mmol/L) and severe hypontraemia (<125 mmol/L) with 7-day mortality after adjustment for stroke type, Oxfordshire Community Stroke Project classification, age, prestroke modified Rankin score and sex. The SOAR and SOAR-Na scores both performed well in predicting inpatient mortality with AUC values of .794 (.78-.81) and .796 (.78-.81), respectively. 7 day mortality showed similar results. Both scores were less predictive in those with chronic kidney disease (CKD) and more so in those with hypoglycaemia. CONCLUSION: The SOAR-Na did not perform considerably better than the SOAR stroke score. However, the performance of SOAR-Na in those with CKD and dysglycaemias requires further investigation. PMID- 27397109 TI - Correction: Insights into the unexpected chemoselectivity in Bronsted acid catalyzed cyclization of isatins with enaminones: convenient synthesis of pyrrolo[3,4-c]quinolin-1-ones and spirooxindoles. AB - Correction for 'Insights into the unexpected chemoselectivity in Bronsted acid catalyzed cyclization of isatins with enaminones: convenient synthesis of pyrrolo[3,4-c]quinolin-1-ones and spirooxindoles' by Hui Xu et al., Chem. Commun., 2016, 52, 8002-8005. PMID- 27397111 TI - Fundamental Frequency Variation in Crying of Mandarin and German Neonates. AB - OBJECTIVES: This study examined whether prenatal exposure to either a tonal or a nontonal maternal language affects fundamental frequency (fo) properties in neonatal crying. STUDY DESIGN: This is a population prospective study. PARTICIPANTS: A total of 102 neonates within the first week of life served as the participants. METHODS: Spontaneously uttered cries (N = 6480) by Chinese (tonal language group) and German neonates (nontonal group) were quantitatively analyzed. For each cry utterance, mean fo and four characteristic variation measures (fo range, fo fluctuation, pitch sigma, and pitch sigma fluctuation) were calculated, averaged for individual neonates, and compared between groups. RESULTS: A multiple analysis of variance highlighted a significant multivariate effect for language group: Wilks lambda = .76, F(6, 95) = 4.96, P < .0001, etap2 = .24. Subsequent univariate analyses revealed significant group differences for fo variation measures, with values higher in the tonal language group. The mean fo did not differ between groups. CONCLUSIONS: Data regarding fo variation in infant cries have been suggested as providing critical insight into the maturity of neurophysiological vocal control. Our findings, alongside with auditive perception studies, further underscore the assumption of an early shaping effect of maternal speech, particularly fo-based features, on cry features of newborns. Further studies are needed to reexamine this observation and to assess its potential diagnostic relevance. PMID- 27397110 TI - Preventative treatment in an animal model of ADHD: Behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats. AB - Clinical and preclinical studies on attention deficit hyperactivity disorder (ADHD) show that juvenile males that are exposed to methylphenidate (MPH) show reduced risk for substance use later in life. In contrast, little is known about whether females have the same enduring treatment response to stimulants and how gonadal hormones influence their behavior later in life. Females received either a sham or 6-hydroxydopamine (6-OHDA) microinjection in the prefrontal cortex (PFC) at postnatal day (P)10. Subjects were then treated with Vehicle or MPH (2mg/kg, p.o.) between P20-35 and tested during late adolescence/young adulthood (P60); half of these subjects underwent ovariectomy at P55 to determine hormonal influences. Females with 6-OHDA were depleted of PFC dopamine by 61% and demonstrated increased impulsive choice (delayed discounting) and preferences for cocaine-associated environments relative to control females. Both MPH and ovariectomy reduced impulsive choice and cocaine preferences in 6-OHDA females, but had no enduring effect in Sham females. Ovariectomy itself did not significantly affect impulsivity. Juvenile MPH interacted strongly with 6-OHDA to increase D4, D5, Alpha-1A, Alpha-2A, and 5-HT-1A mRNA receptor expression in the PFC. MPH alone effected D1 mRNA, while 6-OHDA increased BDNF; all markers were decreased by ovariectomy. Together, these data suggest that 6-OHDA changes in dopamine are not only relevant for ADHD-like behaviors, but their long-term modulation by treatment and the influence of cyclical differences in menstrual cycle. PMID- 27397112 TI - The Psychometric Properties of the Voice Handicap Index in People With Parkinson's Disease. AB - BACKGROUND: Psychosocial impact of dysphonia in people with Parkinson disease (PD) has been described with the Voice Handicap Index (VHI); however, its psychometric properties when applied in this population are not described. OBJECTIVE: The objective of this study was to examine the psychometric properties of the VHI in people with PD. METHODS: A cross-sectional study of 151 subjects without cognitive impairment (90 people with PD and 61 controls) was carried out. The VHI was applied along with clinician-based (Mini Mental State Examination, Hoehn and Yahr staging, and Movement Disorder Society-Unified Parkinson's Disease Rating Scale) and patient-based (self-rated voice severity) outcome measures. The psychometric properties of the VHI analyzed were the feasibility, reliability, and construct validity. RESULTS: The average age of the PD population studied was 67 years; 51% had a primary level of education and 81% were retired. On average, they had disease onset duration of 11 years, a mild disease stage, mild to moderate global motor disability and impairment, and a normal to mild self-rated voice severity. The psychometric attributes of the VHI demonstrated that the questionnaire is feasible (missing data less than 1%), reliable (Cronbach alpha > 0.9), and valid (71.5% of the total variance is explained by five factors, correlates with voice severity, PD disability, and impairment, and differentiates subjects with PD from subjects without PD). CONCLUSION: The VHI is a reliable and valid tool that can be recommended for the population under study although further work is required to investigate its utility in advanced stages of disease. PMID- 27397113 TI - Human Speech: A Restricted Use of the Mammalian Larynx. AB - PURPOSE: Speech has been hailed as unique to human evolution. Although the inventory of distinct sounds producible with vocal tract articulators is a great advantage in human oral communication, it is argued here that the larynx as a sound source in speech is limited in its range and capability because a low fundamental frequency is ideal for phonemic intelligibility and source-filter independence. METHOD: Four existing data sets were combined to make an argument regarding exclusive use of the larynx for speech: (1) range of fundamental frequency, (2) laryngeal muscle activation, (3) vocal fold length in relation to sarcomere length of the major laryngeal muscles, and (4) vocal fold morphological development. RESULTS: Limited data support the notion that speech tends to produce a contracture of the larynx. The morphological design of the human vocal folds, like that of primates and other mammals, appears to be optimized for vocal communication over distances for which higher fundamental frequency, higher intensity, and fewer unvoiced segments are used. CONCLUSION: The positive message is that raising one's voice to call, shout, or sing, or executing pitch glides to stretch the vocal folds, can counteract this trend toward a contracted state. PMID- 27397114 TI - Predicting Post-Concussion Symptom Risk in the ED. AB - Investigators from The Pediatric Emergency Research Canada (PERC) Concussion Team developed a clinical risk score for predicting persistent post-concussion symptoms (PPCS) at 28 days post injury in a large cohort of children initially evaluated at the emergency department (ED) within 48 hours of injury. PMID- 27397115 TI - Chemistry and Structure of Graphene Oxide via Direct Imaging. AB - Graphene oxide (GO) and reduced GO (rGO) are the only variants of graphene that can be manufactured at the kilogram scale, and yet the widely accepted model for their structure has largely relied on indirect evidence. Notably, existing high resolution transmission electron microscopy (HRTEM) studies of graphene oxide report long-range order of sp(2) lattice with isolated defect clusters. Here, we present HRTEM evidence of a different structural form of GO, where nanocrystalline regions of sp(2) lattice are surrounded by regions of disorder. The presence of contaminants that adsorb to the surface of the material at room temperature normally prevents direct observation of the intrinsic atomic structure of this defective GO. To overcome this, we use an in situ heating holder within an aberration-corrected TEM (AC-TEM) to study the atomic structure of this nanocrystalline graphene oxide from room temperature to 700 degrees C. As the temperature increases to above 500 degrees C, the adsorbates detach from the GO and the underlying atomic structure is imaged to be small 2-4 nm crystalline domains within a polycrystalline GO film. By combining spectroscopic evidence with the AC-TEM data, we support the dynamic interpretation of the structural evolution of graphene oxide. PMID- 27397117 TI - True Brachial Artery Aneurysm. PMID- 27397116 TI - Transcranial Doppler Ultrasound Detection of Microemboli as a Predictor of Cerebral Events in Patients with Symptomatic and Asymptomatic Carotid Disease: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Identification of patients who will benefit from carotid endarterectomy is not entirely effective, primarily utilising degree of carotid stenosis. This study aimed at determining if microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) can provide clinically useful information regarding stroke risk in patients with carotid atherosclerosis. METHODS: A meta-analysis of prospective studies was performed. Three analyses were proposed investigating MES detection as a predictor of: stroke or TIA, stroke alone, and stroke or TIA but with an increased positivity threshold. Subgroup analysis was used to compare pre-operative (symptomatic or asymptomatic) patients and peri- or post-operative patients. RESULTS: Twenty-eight studies reported data regarding both MES status and neurological outcome. Of these, 22 papers reported data on stroke and TIA as an outcome, 19 on stroke alone, and eight on stroke and TIA with increased positivity threshold. At the median pre test probability of 3.0%, the post-test probabilities of a stroke after a positive and negative TCD were 7.1% (95% CI 5-10.1) and 1.2% (95% CI 0.6-2.5), respectively. In addition, the sensitivities and specificities of each outcome showed that increasing the threshold for positivity to 10 MES per hour would make TCD a more clinically useful tool in peri- and post-operative patients. CONCLUSION: TCD provides clinically useful information about stroke risk for patients with carotid disease and is technically feasible in most patients. However, the generally weak level of evidence constituting this review means definitive recommendations cannot be made. PMID- 27397118 TI - Ultrasonic Technology Improves Radial Artery Puncture and Cannulation in Intensive Care Unit (ICU) Shock Patients. AB - BACKGROUND This study observed the efficacy of ultrasonic technique with out-of plane orientation and in-plane guidance in radial artery puncture and cannulation in intensive care unit (ICU) shock patients to elucidate the effect of this technique on the security of cannulation. MATERIAL AND METHODS A total of 88 ICU shock patients, randomized into a palpation (control) group and an ultrasound (experimental) group, received continuous intravenous sedation and analgesia. The palpation group patients underwent radial artery cannulation using the traditional palpation pulsation approach, and the ultrasound group patients underwent radial artery cannulation under out-of-plane orientation and in-plane guidance using an ultrasonic apparatus. Data were recorded and compared between the 2 groups. RESULTS (1) The success rate of the first puncture in the ultrasound group and the palpation group was 80% and 42%, respectively (P<0.05). (2) The cannulation duration in the ultrasound group and the palpation group was 8.77+/-6.33 s and 28.7+/-26.33 s, respectively (P<0.01). (3) Incidence of hematoma and staxis around stoma in the ultrasound group was 2.5% and 5%, respectively, which was significantly lower than that in the palpation group, which was 20% and 32.5%, respectively (P<0.05). (4) Time to achieve the early goal-directed therapy in the ultrasound group and the palpation group was 306.73+/-39.98 min and 356.75+/-40.97 min, respectively (P<0.01). CONCLUSIONS Compared with the traditional method, radial artery cannulation with out-of-plane orientation and in-plane guidance is a quick and secure cannulation method and is appropriate for use in clinics. PMID- 27397120 TI - Editor's mail. PMID- 27397119 TI - Time-dependent summary receiver operating characteristics for meta-analysis of prognostic studies. AB - Prognostic studies are widely conducted to examine whether biomarkers are associated with patient's prognoses and play important roles in medical decisions. Because findings from one prognostic study may be very limited, meta analyses may be useful to obtain sound evidence. However, prognostic studies are often analyzed by relying on a study-specific cut-off value, which can lead to difficulty in applying the standard meta-analysis techniques. In this paper, we propose two methods to estimate a time-dependent version of the summary receiver operating characteristics curve for meta-analyses of prognostic studies with a right-censored time-to-event outcome. We introduce a bivariate normal model for the pair of time-dependent sensitivity and specificity and propose a method to form inferences based on summary statistics reported in published papers. This method provides a valid inference asymptotically. In addition, we consider a bivariate binomial model. To draw inferences from this bivariate binomial model, we introduce a multiple imputation method. The multiple imputation is found to be approximately proper multiple imputation, and thus the standard Rubin's variance formula is justified from a Bayesian view point. Our simulation study and application to a real dataset revealed that both methods work well with a moderate or large number of studies and the bivariate binomial model coupled with the multiple imputation outperforms the bivariate normal model with a small number of studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27397121 TI - Prospectus a rated guide to CME courses. AB - POSTGRADUATE MEDICINE offers as a regular reader service this objectively rated, expanded listing of meetings and courses that are designed for primary care physicians. We hope that the detailing of pertinent information will aid physicians in selecting activities to further their continuing medical education. Meetings are awarded one to four stars on the basis of the following criteria: relevance of program content to our readership, accreditation, cost per credit hour (registration fee only), sponsorship, and meeting site. Institutions and associations wishing to have a CME event listed in this calendar should provide the necessary information well in advance of the event (preferably four months before). Correspondence should be addressed to: Prospectus Editor, Editorial Department, POSTGRADUATE MEDICINE. 4530 W 77th St, Minneapolis, MN 55435. PMID- 27397122 TI - Problems Solutions. PMID- 27397123 TI - Research reports. PMID- 27397124 TI - Washington background. PMID- 27397125 TI - Physician-at-large. PMID- 27397126 TI - Coming in postgraduate medicine. PMID- 27397127 TI - Readysource hip and Leg Problems in Children. AB - ReadySource is intended for the reader who wishes more information on or education in the particular subject area. it is drawn from several sources: the Educational Resource Index, a computerized listing developed by the Department of Continuing Education, University of Wisconsin-Extension; announcements by individual medical schools and teaching hospitals; information provided by the author; and our own files. Listing does not necessarily imply endorsement by the university, POSTGRADUATE MEDICINE, or the author of the article. Readers interested in a meeting or audiovisual aid should write directly to the contact listed. PMID- 27397128 TI - Cme credit quiz. PMID- 27397129 TI - Traumatic injuries. AB - Eye injury caused by foreign materials may be inconsequential or severe. The primary physician must rapidly assess the nature and extent of injury in relation to the causative agent to determine whether general office treatment will suffice or if the patient must be referred to an ophthalmologist. PMID- 27397131 TI - Answers cme credit quiz september 1976. PMID- 27397133 TI - Reported prevalence of gestational diabetes in Scotland: The relationship with obesity, age, socioeconomic status, smoking and macrosomia, and how many are we missing? AB - AIMS/INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as 'carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy,' and is associated with increased fetal and maternal risks. The aims of the present study were to investigate the prevalence of GDM in Scotland over 32 years (1981-2012), and using the data from 2012, to assess how GDM related to maternal body mass index, maternal age, parity, smoking, Scottish Index of Multiple Deprivation, infant gender and macrosomia status. MATERIALS AND METHODS: GDM prevalence along with anthropometric, obstetric and demographic data were collected on a total of 1,891,097 women with a delivery episode between 1 January 1981 and 31 December 2012 using data extracted from the Scottish Morbidity Record 02. Univariate and multivariate logistic regression analysis was undertaken to investigate their association with GDM. RESULTS: A ninefold increase in GDM prevalence was observed from 1981 to 2012 (P < 0.001). GDM prevalence in 2012 was 1.9%. Maternal body mass index, age, parity status, Scottish index of multiple deprivation and fetal macrosomia were positively associated with GDM. Reported smoking status at booking was inversely associated with GDM. Multivariable analysis showed that fetal macrosomia was not associated with GDM status. CONCLUSIONS: The present study confirmed that the reporting of GDM is low in Scotland, and that GDM is associated with maternal body mass index, maternal age, multiparity and social deprivation. GDM was negatively associated with smoking and requires further investigation. The lack of association between GDM and macrosomia (following multivariate analysis) might reflect the screening processes undertaken in Scotland. PMID- 27397134 TI - Hydroxyapatite nanocrystals as a smart, pH sensitive, delivery system for kiteplatin. AB - Hydroxyapatite (HA) nanocrystals are important inorganic constituents of biological hard tissues in vertebrates and have been proposed as a bone substitute or a coating material for prostheses in biomedicine. Hydroxyapatite is also amenable for its capacity to bind to a great variety of biomolecules and therapeutic agents. As drug carriers, apatite nanoparticles also have the advantage of pH dependent solubility and low toxicity. Thus HA nanoparticles are negligibly soluble at physiological pH but their dissolution is accelerated at lower pH such as that typically found in the vicinity of tumors. In the present study we have investigated the adsorption on and the release from biomimetic HA nanoparticles of two platinum derivatives of cis-1,4-diaminocyclohexane ([PtX2(cis-1,4-DACH)], X2 = Cl2 (1) and 1,1-cyclobutanedicarboxylate (CBDCA, 2)). The first of the two compounds proved to be active against colon cancer cells also resistant to oxaliplatin. The release has been investigated as a function of pH to mimic the different physiological environments of healthy tissues and tumors, and the in vitro cytotoxicity of the releasates from the HA matrices has been assessed against various human cancer cell lines. The results fully confirmed the potential of 1-loaded HA nanoparticles as bone-specific drug delivery devices. PMID- 27397136 TI - On the utility of meta-analyses in the study of natural selection. PMID- 27397135 TI - Human dignity and professional reputation under threat: Iranian Nurses' experiences of workplace violence. AB - Workplace violence against nurses is a challenging problem in both developed and developing countries. Because the concept of violence bears some cultural load, nurses' understanding is region-specific. This study explores Iranian nurses' perceptions of workplace violence. Using qualitative content analysis, 22 registered nurses underwent unstructured, in-depth interviews. The main themes of threats to human dignity and professional reputation emerged, plus four categories: physical violence, psychological violence, honor insults, and ethnic religious insults. The term "honor insults," as a unique finding, was used instead of "sexual harassment." These findings may help to redefine workplace violence based on cultural background, design strategies for supporting nurses, and prevent and manage such violence. PMID- 27397137 TI - Electronic cigarette explosion associated with extensive intraoral injuries. AB - With the rise in popularity of usage of various electronic smoking devices, there have been increasing reports of explosions, often resulting in complex injuries to the head and neck. To promote the awareness of this new phenomenon, a case report is provided regarding an 18-year-old male who had an electronic cigarette explode in his mouth. He presented with severe damage to the anterior dentition (fractured teeth, avulsions, luxation), had fractured the premaxilla and anterior nasal spine, and sustained lacerations to the upper lip, labial mucosa, gingivae, tongue, hard palate, and facial skin. PMID- 27397138 TI - Dynamic Bayesian Network for Accurate Detection of Peptides from Tandem Mass Spectra. AB - A central problem in mass spectrometry analysis involves identifying, for each observed tandem mass spectrum, the corresponding generating peptide. We present a dynamic Bayesian network (DBN) toolkit that addresses this problem by using a machine learning approach. At the heart of this toolkit is a DBN for Rapid Identification (DRIP), which can be trained from collections of high-confidence peptide-spectrum matches (PSMs). DRIP's score function considers fragment ion matches using Gaussians rather than fixed fragment-ion tolerances and also finds the optimal alignment between the theoretical and observed spectrum by considering all possible alignments, up to a threshold that is controlled using a beam-pruning algorithm. This function not only yields state-of-the art database search accuracy but also can be used to generate features that significantly boost the performance of the Percolator postprocessor. The DRIP software is built upon a general purpose DBN toolkit (GMTK), thereby allowing a wide variety of options for user-specific inference tasks as well as facilitating easy modifications to the DRIP model in future work. DRIP is implemented in Python and C++ and is available under Apache license at http://melodi lab.github.io/dripToolkit . PMID- 27397139 TI - Challenges to HIV management among youth engaged in HIV care. AB - Regardless of medical advancements, new HIV infections persist. Young adults are most often newly infected, thus research is needed to assess medication adherence barriers specific to young adults with HIV. The data were abstracted from medical charts to include both self-reported behavioral and psychological distress data and HIV parameters in 2013 among patients aged 18-30 years. Descriptive and logistic regression analyses were conducted to identify factors related to viral suppression and sexually transmitted infection (STI) status. A total of 335 individuals presented for care during a 12-month period at a single clinic. The majority were African American and had a mean age of 25.6 years. Nearly all had current prescriptions of antiretroviral therapy (ART). Among those receiving ART, almost three-quarters were virally suppressed, as measured by 200 copies/mL. STI tests are conducted annually and by assessed need; 30% of this sample had at least 1 bacterial STI diagnosis within the last year. Psychological distress symptoms were more common among individuals who were not virally suppressed, compared to those who were virally suppressed. Women and individuals with moderate to severe symptoms of depression had higher odds of having unsuppressed viral loads. The independent factors associated with having any STIs were being African American or other minorities and having two or more sex partners. Our findings related to how young adults are managing their HIV care suggest that increased efforts aimed to prevent additional STIs and manage psychological distress will likely reduce transmission risks. PMID- 27397140 TI - Perioperative morbidity in children with elastin arteriopathy. AB - BACKGROUND: Children with elastin arteriopathy (EA), the majority of whom have Williams-Beuren syndrome, are at high risk for sudden death. Case reports suggest that the risk of perioperative cardiac arrest and death is high, but none have reported the frequency or risk factors for morbidity and mortality in an entire cohort of children with EA undergoing anesthesia. AIM: The aim of this study was to present one institution's rate of morbidity and mortality in all children with EA undergoing anesthesia and to examine patient characteristics that pose the greatest risk. METHODS: We reviewed medical records of children with EA who underwent anesthesia or sedation for any procedure at our institution from 1990 to 2013. Cardiovascular hemodynamic indices from recent cardiac catheterization or echocardiography were tabulated for each child. The incidence, type, and associated factors of complications occurring intraoperatively through 48 h postoperatively were examined. RESULTS: Forty-eight patients with confirmed EA underwent a total of 141 anesthetics. There were seven cardiac arrests (15% of patients, 5% of anesthetics) and nine additional intraoperative cardiovascular complications (15% of patients, 6% of anesthetics). Extracorporeal life support was initiated in five cases. There were no perioperative deaths. All children having a cardiac arrest or complication were <3 years old and had biventricular outflow tract obstruction (BVOTO). Subgroup analysis demonstrated high rates of cardiac arrest in two groups: children with BVOTO (44%) and age <3 years old (21%). CONCLUSIONS: We have confirmed that the rate of cardiac arrest and complications is significantly elevated in children with EA undergoing anesthesia. Children <3 years old and with BVOTO were at the greatest risk in our population. PMID- 27397141 TI - Late relapse of primary central nervous system lymphoma. PMID- 27397143 TI - Relationship between maceration and wound healing on diabetic foot ulcers in Indonesia: a prospective study. AB - The aim of this study was to clarify the relationship between maceration and wound healing. A prospective longitudinal design was used in this study. The wound condition determined the type of dressings used and the dressing change frequency. A total of 62 participants with diabetic foot ulcers (70 wounds) were divided into two groups: non-macerated (n = 52) and macerated wounds (n = 18). Each group was evaluated weekly using the Bates-Jensen Wound Assessment Tool, with follow-ups until week 4. The Mann-Whitney U test showed that the changes in the wound area in week 1 were faster in the non-macerated group than the macerated group (P = 0.02). The Pearson correlation analysis showed a moderate correlation between maceration and wound healing from enrolment until week 4 (P = 0.002). After week 4, the Kaplan-Meier analysis showed that the non-macerated wounds healed significantly faster than the macerated wounds (log-rank test = 19.378, P = 0.000). The Cox regression analysis confirmed that maceration was a significant and independent predictor of wound healing in this study (adjusted hazard ratio, 0.324; 95% CI, 0.131-0.799; P = 0.014). The results of this study demonstrated that there is a relationship between maceration and wound healing. Changes in the wound area can help predict the healing of wounds with maceration in clinical settings. PMID- 27397144 TI - Astragaloside I Stimulates Osteoblast Differentiation Through the Wnt/beta catenin Signaling Pathway. AB - Astragaloside I (As-I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As-I-induced osteogenic effects and its underlying mechanism were studied in MC3T3-E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose-dependent manner by As-I. To clarify the mechanisms involved in this process, the effect of As-I on the key osteogenic-related genes was investigated. We found that As-I stimulated the expression of beta-catenin and Runx2 in MC3T3-E1 cells, which play central roles in the Wnt/beta-catenin signaling pathway, suggesting that As-I could promote osteoblastic differentiation by regulating the Wnt/beta-catenin signaling pathway. Moreover, the osteogenic effect of As-I could be inhibited by DKK-1, which is the classical inhibitor of Wnt/beta-catenin-signaling pathway. Furthermore, As-I also increased BMP-2, BGP and OPG/RANKL expression, which are also activated by Wnt/beta-catenin signaling pathway. Taken together, our findings show that As-I stimulates osteoblast differentiation through the Wnt/beta-catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As-I for pharmaceutical and medicinal applications such as treating bone disease. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27397145 TI - A Rapid and Simple LC-MS Method Using Collagen Marker Peptides for Identification of the Animal Source of Leather. AB - Identification of the animal source of leather is difficult using traditional methods, including microscopic observation and PCR. In the present study, a LC-MS method was developed for detecting interspecies differences in the amino acid sequence of type I collagen, which is a major component of leather, among six animals (cattle, horse, pig, sheep, goat, and deer). After a dechroming procedure and trypsin digestion, six tryptic peptides of type I collagen were monitored by LC-MS in multiple reaction monitoring mode for the animal source identification using the patterns of the presence or absence of the marker peptides. We analyzed commercial leathers from various production areas using this method, and found some leathers in which the commercial label disagreed with the identified animal source. Our method enabled rapid and simple leather certification and could be applied to other animals whether or not their collagen sequences are available in public databases. PMID- 27397146 TI - Oscillatory multiphase flow strategy for chemistry and biology. AB - Continuous multiphase flow strategies are commonly employed for high-throughput parameter screening of physical, chemical, and biological processes as well as continuous preparation of a wide range of fine chemicals and micro/nano particles with processing times up to 10 min. The inter-dependency of mixing and residence times, and their direct correlation with reactor length have limited the adaptation of multiphase flow strategies for studies of processes with relatively long processing times (0.5-24 h). In this frontier article, we describe an oscillatory multiphase flow strategy to decouple mixing and residence times and enable investigation of longer timescale experiments than typically feasible with conventional continuous multiphase flow approaches. We review current oscillatory multiphase flow technologies, provide an overview of the advancements of this relatively new strategy in chemistry and biology, and close with a perspective on future opportunities. PMID- 27397147 TI - The final act-a? PMID- 27397148 TI - Brainwaves. PMID- 27397149 TI - The neuroscience of consciousness. PMID- 27397150 TI - The NSW Tissue Resource Centre (brain bank) and donor programs: their development and importance for neuropsychiatric research. PMID- 27397151 TI - The long and winding road of schizophrenia research. PMID- 27397152 TI - Mental health literacy: the inside story of a research program. PMID- 27397153 TI - What do we know about the genetics of depression? PMID- 27397154 TI - New insights from cross-linked data on the relationship between psychotic illness and intellectual disability. PMID- 27397155 TI - Dynamin's role in synaptic transmission: a potential target for new antiepileptic drugs. PMID- 27397156 TI - First-episode psychosis and direction of wave propagation at 1 Hz in the EEG. PMID- 27397157 TI - Psychotic-like experiences in a community sample of adolescents: associations with distress, depression and functioning. PMID- 27397158 TI - Stability of psychotic-like experiences over 6 months in a clinical sample of non psychotic young people. PMID- 27397159 TI - Investigating the 'trill of suspirality': thought disorder as an emergent property of conversational interaction. PMID- 27397160 TI - Association of cytokines and cognitive functioning in the elderly general population. PMID- 27397161 TI - The COMT val158met genetic variant predicts antidepressant treatment response in major depression. PMID- 27397162 TI - Childhood trauma and psychosis: a critical review. PMID- 27397163 TI - The impact of age at onset of bipolar 1 disorder on functioning and clinical presentation. PMID- 27397165 TI - The multiscale hypothesis of bipolar disorder. PMID- 27397164 TI - Neuropsychological function in social phobia. PMID- 27397166 TI - Referential delusions of communication and self-monitoring deficits in psychosis. PMID- 27397167 TI - Reduced psychoacoustic sensitivity to auditory temporal stimulation in schizophrenia reflects cytoarchitecturally specific changes in auditory cortex. PMID- 27397168 TI - Mental health problems within couples and marital disruption. PMID- 27397169 TI - A comparison of the neuropsychological and neurological correlates of childhood, adolescent and adult bipolar disorders. PMID- 27397170 TI - Screening and treatment for depression during pregnancy: a cautionary note. PMID- 27397171 TI - Patient predictors of response to interpersonal psychotherapy and cognitive behaviour therapy. PMID- 27397173 TI - Models of health care delivery for depression. PMID- 27397172 TI - White matter hyperintensities: lateralization effects. PMID- 27397174 TI - The Illness Management and Recovery Program: an international effectiveness study. PMID- 27397175 TI - Constructing longitudinal measures of maternal morbidity using a population health database: is use of the index birth record sufficient to identify obstetric risk factors for schizophrenia? PMID- 27397176 TI - Altered tripartite synapse function: is this the problem in schizophrenia and bipolar disorder? PMID- 27397177 TI - Time course of illness prior to a diagnosis of bipolar disorder or schizoaffective disorder. PMID- 27397178 TI - A central dilemma in the mental health sector: structural imbalance. PMID- 27397179 TI - Anxiety, depression and the HPA axis in human pregnancy: links to postpartum mood. PMID- 27397180 TI - Phenotypic correlates of the serotonin transporter gene. PMID- 27397181 TI - Clozapine and cardiotoxicity: echocardiography findings from Barwon Health. PMID- 27397182 TI - Gamma synchrony in first-episode psychosis. PMID- 27397183 TI - Duration of untreated psychosis: the relative contribution of individual vs. community factors. PMID- 27397184 TI - Multimodal imaging of the mismatch negativity deficit in schizophrenia. PMID- 27397185 TI - Investigation of circadian disruption in bipolar disorder. PMID- 27397186 TI - Silence is golden? Improving cognitive performance in schizophrenia. PMID- 27397187 TI - Can consent be uninformed? Suggested reform of sexual offences against persons with mental impairment. PMID- 27397188 TI - Cognition and volition: a melancholic condition. PMID- 27397189 TI - Childhood risk for obsessive compulsive disorder. PMID- 27397190 TI - A closer look at melancholia: saccadic eye movements in melancholic and nonmelancholic depression. PMID- 27397191 TI - Cognitive remediation in first-episode and chronic schizophrenia. PMID- 27397192 TI - Atypical antipsychotic use in Australian patients: cross-sectional study of uptake and perceived benefit. PMID- 27397193 TI - A comparison of the implementation of assertive community treatment in Melbourne and London. PMID- 27397194 TI - The impact of the introduction of an acute sedation practice guideline. PMID- 27397195 TI - Wagging the black dog: predicting depression severity using neuropsychological measures. PMID- 27397196 TI - The mental health and well-being of rural people: a pilot study measuring community factors. PMID- 27397197 TI - Adolescent alcohol use and mobile phone experience sampling in a clinical setting: an innovative, youth friendly approach to research. PMID- 27397198 TI - The SHADE Project: self-help for alcohol/other drug use and depression. PMID- 27397199 TI - Mental health first aid standards for self-harm. PMID- 27397200 TI - Vocational rehabilitation in first-episode psychosis: results of the first Australian randomized controlled trial of individual placement and support. PMID- 27397201 TI - Diagnosing mild cognitive impairment - a data-driven approach. PMID- 27397202 TI - The effects of adjunctive estradiol on cognitive performance in women with schizophrenia. PMID- 27397203 TI - Tamoxifen - a potential treatment for women in the manic phase of bipolar affective disorder? PMID- 27397204 TI - The use of selective estrogen receptor modulators in the treatment of menopausal women with schizophrenia. PMID- 27397205 TI - The estrogen 100. PMID- 27397206 TI - Using theories of delusion formation to explain abnormal thinking in patients with body dysmorphic disorder. PMID- 27397207 TI - One-year estimate of depot antipsychotic adherence and readmission in Victorian community mental health settings. PMID- 27397208 TI - The metabolic syndrome in patients with a prolonged psychotic illness within a community setting: age and gender issues. PMID- 27397209 TI - Stability of antipsychotic prescribing: description and relationship to readmission. PMID- 27397210 TI - Psychostimulant withdrawal: natural history and options for intervention. PMID- 27397211 TI - Identification of a bipolar disorder susceptibility locus on chromosome 15Q. PMID- 27397212 TI - A blinded, placebo-controlled randomized trial of low-dose risperidone, intensive psychological treatment and befriending in young people at risk of psychotic disorder: baseline characteristics of the sample. PMID- 27397213 TI - The defensive function of persecutory delusions: an investigation using the Implicit Association Test. PMID- 27397214 TI - Impaired psychosocial functioning in bipolar disorder: the relative contributions of inter-episodic symptoms and illness episodes. PMID- 27397215 TI - A factor analytic study in bipolar depression, and response to lamotrigine. PMID- 27397216 TI - Evaluation of MoodGYM with an adolescent population. PMID- 27397217 TI - Visual field semantic priming and relationship with thought disorder. PMID- 27397218 TI - When things are not as they seem: detecting first-episode psychosis upon referral to ultrahigh-risk ('prodromal') clinics. PMID- 27397219 TI - Obsessive compulsive disorder: time to decide on a new model? PMID- 27397220 TI - They never forget: recall of traumatic memories of Vietnam. PMID- 27397221 TI - The prevalence of PTSD in Australian Vietnam Veterans 35 years after war's end: preliminary results of a cohort study. PMID- 27397222 TI - Identifying affective markers of ADHD and comorbid Conduct Disorder. PMID- 27397223 TI - Do religious beliefs help us cope with traumatic experiences? PMID- 27397224 TI - Modelling pre-trauma resilience and vulnerability factors for PTSD. PMID- 27397225 TI - Clozapine invokes the EGF system to activate ERK: a novel target in treatment resistant schizophrenia? PMID- 27397226 TI - The prevalence of depression in the North West Adelaide Health Study. PMID- 27397227 TI - Use of the web in the self-management of bipolar disorder. PMID- 27397228 TI - Keeping Care Complete: results from the first international schizophrenia and bipolar disorder family caregivers survey. PMID- 27397229 TI - A randomized controlled trial to assess the efficacy of omega-3 fatty acids as a treatment for depression during the perinatal period. PMID- 27397230 TI - Understanding how young people cope with distress: the development of a mobile phone momentary sampling program (Mobile_TYPE). PMID- 27397231 TI - Using ketamine to model thought disorder in schizophrenia. PMID- 27397232 TI - Behavioural and fMRI evidence of semantic category deficits in schizophrenia. PMID- 27397233 TI - Jumping to conclusions in delusions: fact or fallacy? PMID- 27397234 TI - Building and evaluating effective mental health networks in rural communities. PMID- 27397235 TI - A taxometric exploration of alcohol and cannabis problems in a community sample. PMID- 27397236 TI - Diagnosing mild cognitive impairment: the problem with subjective complaints. PMID- 27397237 TI - Collective trauma: the case for a multilevel social-ecological perspective. PMID- 27397238 TI - Multilevel modeling of rural mental health. PMID- 27397239 TI - Prevalence of mental disorders in the elderly: the Australian National Mental Health and Well-being Survey. PMID- 27397240 TI - Innovative ways of treating comorbid diabetes type II and depression: piloting the 'MADE-IT' program. PMID- 27397241 TI - Complex mental activity and risk for dementia. PMID- 27397242 TI - Degeneration vs. degeneracy: a neural systems approach to functional reorganization. PMID- 27397243 TI - Modeling risk from conception to disease: issues in the design of a population health database for psychiatric research. PMID- 27397244 TI - Integrating vocational services into Australian community mental health services. PMID- 27397245 TI - Risk factors for physical inactivity across the adult life span: the impact of depression. PMID- 27397246 TI - Factors influencing the decision to learn 5-HTT genotype results and subsequent impact on the individual. PMID- 27397247 TI - Understanding altered neural synchrony in first-episode schizophrenia. PMID- 27397248 TI - Happy trails to you - a review of subjective well-being in successful aging. PMID- 27397249 TI - Behavioural problems following stroke - is there a relationship with cognitive impairment? PMID- 27397250 TI - A T2-relaxometric investigation of the brain in early psychosis: preliminary findings. PMID- 27397251 TI - Anxiety and personality structure among Malay students. PMID- 27397252 TI - Investigation of the Repeatable Battery for the Assessment of Neuropsychological Status scores in an Australian community sample of brain donors with schizophrenia. PMID- 27397253 TI - Elucidating semantic disorganization from word comprehension: do patients with schizophrenia and bipolar disorder show differential processing of nouns, verbs and adjectives? PMID- 27397254 TI - The response to sulpiride in major depression before and after cognitive behavioural therapy: D2 receptor function. PMID- 27397255 TI - The Clinical Global Impressions Scale Modified for Substance Use (CGI-SU) in patients with bipolar disorder. PMID- 27397256 TI - The impact of accommodation status on the hospitalization of mentally ill patients. PMID- 27397257 TI - Keep the heart in mind: the interplay of heart and brain activity over the life span. PMID- 27397258 TI - Reduced fMRI activity in response to salient stimuli in first-episode schizophrenia. PMID- 27397259 TI - Functional brain imaging of auditory prepulse inhibition. PMID- 27397260 TI - Values of cross-cultural research: insights gained from the validation of the 'Depression Screening Measure DMI-10 Chinese version'. PMID- 27397261 TI - Problem gambling - prevalence and mental health aspects in a psychiatric setting. PMID- 27397263 TI - Judged effectiveness of treatments for depression: a web-based survey. PMID- 27397262 TI - Obesity and metabolic syndrome in a psychiatric rehabilitation service. PMID- 27397264 TI - The neuropsychological consequences of cannabis use in schizophrenia: a preliminary analysis. PMID- 27397265 TI - Impaired connectivity in amygdala pathways may explain disorganization symptoms of patients with first-episode schizophrenia. PMID- 27397266 TI - Patterns and predictors of aggressive incidents in children and adolescents admitted to a mental health in-patient unit. PMID- 27397267 TI - Antidepressants in children and adolescents - changes in utilization after safety warnings. PMID- 27397268 TI - Orbitoprefrontal dysfunction and aggression in war veterans with post-traumatic stress disorder. PMID- 27397269 TI - Converging evidence from taxometric analyses confirms a cognitive subtype of schizophrenia with distinct genetic basis. PMID- 27397270 TI - Coregulation of genes in the mouse brain following antipsychotic drug treatment. PMID- 27397271 TI - The Australian Biomarkers Lifestyle and Imaging flagship study of ageing. PMID- 27397272 TI - Clozapine - fatal constipation more common than fatal agranulocytosis. PMID- 27397273 TI - Age differences in mental health literacy. PMID- 27397274 TI - A randomized double-blind trial of right prefrontal cortex low-frequency transcranial magnetic stimulation in major depression. PMID- 27397275 TI - A meta-analytic study of changes in brain activation in depression. PMID- 27397276 TI - An fMRI study of the effects of low- and high-frequency transcranial magnetic stimulation treatment in depression. PMID- 27397277 TI - Outcome in a specialist referral clinic for mood disorders: a qualitative and quantitative review. PMID- 27397278 TI - First-episode psychosis in the community in NSW: detection and service utilization. PMID- 27397280 TI - Reduced interhemispheric connectivity in the central auditory system of patients with auditory hallucinations. PMID- 27397279 TI - A dissociation of structure and function in the auditory cortex of patients with schizophrenia. PMID- 27397281 TI - Responding to deliberate self-harm among school students: the development and evaluation of evidence-based training. PMID- 27397282 TI - Increasing clinical monitoring of metabolic health in patients treated with antipsychotic medication. PMID- 27397283 TI - Perceived burden in carers of patients with mild Alzheimer's disease: the effect of patient insight. PMID- 27397284 TI - e-couch: the mother of all emental health web sites. PMID- 27397285 TI - Predictors of suicide in major depressive disorder: a follow-up of patients seen at a specialist mood disorders unit. PMID- 27397286 TI - Bipolar disorder and the TCI. PMID- 27397287 TI - Orosomucoid influences both antidepressant tolerance and response. PMID- 27397288 TI - Development of an antenatal intervention package for women with serious mental illness. PMID- 27397289 TI - Participatory action research: researching with disenfranchised populations. PMID- 27397290 TI - Validation of a pencil-and-paper measure for depression in the cardiac population: the DMI-10 and DMI-18. PMID- 27397291 TI - Neurological soft signs in schizophrenia: using transcranial magnetic stimulation to investigate motor overflow. PMID- 27397292 TI - Central auditory processing deficits in patients with auditory hallucinations as shown by event-related potentials: preliminary results. PMID- 27397294 TI - Facial emotion processing in psychosis. PMID- 27397293 TI - Self-reported depression and reduced bone mineral density in a community sample of men: Geelong Osteoporosis Study. PMID- 27397296 TI - Duloxetine in the treatment of melancholic depression. PMID- 27397295 TI - The SHADE project: self-help for alcohol/other drug use and depression. PMID- 27397297 TI - Censoring of prescribable doses: the case of risperidone long-acting injection. PMID- 27397298 TI - Evolving trends in antipsychotic use in two major centers: 1998-2006. PMID- 27397299 TI - Antipsychotic prescribing trends in community treatment of schizophrenia: 1998 2003. PMID- 27397300 TI - Gender bias in the measurement of anxiety and depression. PMID- 27397301 TI - PsyCheck: responding to mental health issues within alcohol and drug treatment. PMID- 27397302 TI - Screening for distress including anxiety and depression in patients with cancer during in-patient admissions. PMID- 27397303 TI - NISAD's 'Gift of Hope' Brain Donor Program: a postmortem brain donor program for people with schizophrenia and allied disorders and those without mental illness. PMID- 27397304 TI - Visual attention to facial features following emotion remediation in schizophrenia. PMID- 27397305 TI - ADHD and first-episode schizophrenia show distinct scanpaths to emotional faces. PMID- 27397306 TI - Twelve women from the National Register of Antipsychotic Medication in Pregnancy. PMID- 27397307 TI - Prevalence and course of depression in cognitively intact and cognitively impaired nursing home residents. PMID- 27397308 TI - Mental health literacy in a community sample of women with eating disorders. PMID- 27397309 TI - The role of mu-opioid receptors in the pathology of schizophrenia. PMID- 27397310 TI - The 21-item Depression Anxiety Stress Scales as a valid routine clinical outcome measure in the private in-patient setting. PMID- 27397311 TI - Pilot study of physical activity in bipolar disorder. PMID- 27397312 TI - The utility of the Clinical Global Impression Scale in the clinical setting. PMID- 27397313 TI - Alzheimer's disease, delusions and cognitive decline. PMID- 27397314 TI - Are affective prosodic deficits evident in bipolar disorder? PMID- 27397315 TI - Omega-3 fatty acids and mood disorders. PMID- 27397317 TI - ECT and neuroprotection: a review and proposed study. PMID- 27397316 TI - Meanings of religion and spirituality for adolescent out-patients. PMID- 27397318 TI - Spatial working memory task validation in a group of patients with schizophrenia and healthy volunteers. PMID- 27397319 TI - Assessment of serotonin function, memory and spatial working memory using buspirone and placebo. PMID- 27397320 TI - Altered neurophysiological parameters in an animal model of hyperactivity. PMID- 27397321 TI - Depression and health risk factors in the North West Adelaide Health Study. PMID- 27397322 TI - Stress Sampler I: psychosocial adjustment and psychiatric and physical comorbidity in diabetes mellitus. PMID- 27397323 TI - Exploring depressive symptoms in mid-adolescence: the integrated effects of life events and personality. PMID- 27397324 TI - Insensitivity to temporal context in schizophrenia. PMID- 27397325 TI - Research priorities in suicide prevention. PMID- 27397326 TI - Adaptation of a resilience program in NSW: the rural RAP. PMID- 27397328 TI - Using the semantic priming task in schizophrenia research: methodological and theoretical considerations. PMID- 27397327 TI - Autumn birth and the cognitive deficit schizophrenia subtype. PMID- 27397329 TI - Reduced dysbindin (DTNBP1) mRNA in hippocampus of patients with schizophrenia. PMID- 27397330 TI - The Stress Sampler Study II: psychological functioning and coping within a diabetes sample. PMID- 27397331 TI - [3H]Pirenzepine binding in the pathology of schizophrenia: studies in Brodmann's area 6. PMID- 27397332 TI - Clinical characterization of brain tissue for neuroscience research: a comparison of antemortem and postmortem diagnoses. PMID- 27397333 TI - Delirium outcomes: is this a time-limited disorder? PMID- 27397335 TI - Depression and anxiety in cardiac rehabilitation patients: characteristics, treatment and outcome. PMID- 27397334 TI - Mismatch negativity in schizophrenia: effect of probability, deviant type and duration of illness. PMID- 27397336 TI - Differential effects of antipsychotic drugs on serotonin-1A receptor-mediated disruption of prepulse inhibition. PMID- 27397337 TI - Longitudinal increases in gamma-phase synchrony contrasts with progressive gray matter atrophy in first-episode schizophrenia. PMID- 27397338 TI - Late-onset bipolar disorder: preliminary results from Sydney. PMID- 27397339 TI - SSRI use and bone mineral density in women with a history of depression: Geelong Osteoporosis Study. PMID- 27397341 TI - Cannabis and Psychosis: From Neuroscience to Clinical Intervention (NISAD Symposium). PMID- 27397340 TI - 'Gift of Hope' - motivation for brain donation into schizophrenia research. PMID- 27397343 TI - 01-02 Cannabis and cognitive function: relevant to psychosis. PMID- 27397342 TI - 01-01 Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of D9-tetrahydrocannabinol. PMID- 27397345 TI - 01-04 Visual scanpath comparisons between those people with and without comorbid cannabis abuse: the implications for eye movement research in schizophrenia. PMID- 27397344 TI - 01-03 fMRI in schizophrenia and cannabis users. PMID- 27397346 TI - 01-05 Cannabis use history and onset to psychosis in an ultrahigh-risk group. PMID- 27397347 TI - 01-06 Cognitive behaviour therapy for substance use disorders in people with psychotic disorders. PMID- 27397348 TI - 01-07 Cannabis use as a complication in psychological treatments for people at ultrahigh risk of psychosis: early findings from the DEPTh trial. PMID- 27397349 TI - Personality Disorders (International Society for the Study of Personality Disorders Symposium). PMID- 27397350 TI - 02-01 Emotion processing and regulation in first-presentation borderline personality disorder. PMID- 27397351 TI - 02-02 Pituitary volume in adolescents with first-presentation borderline personality disorder. PMID- 27397352 TI - 02-03 An MRI study of pituitary volume and suicidal behaviour in adolescents with first-presentation borderline personality disorder. PMID- 27397353 TI - 02-04 Interpersonal functioning in borderline personality disorder: the role of attachment, self-schema and social cognition. PMID- 27397354 TI - 02-05 The relationship of self-structure, attachment style and rejection sensitivity to borderline personality features. PMID- 27397355 TI - 02-06 Personality disorder in the elderly and the effect on outcome of comorbid axis I disorder. PMID- 27397356 TI - 02-07 The effect of personality disorder on treatment for depression: psychotherapy vs. medication. PMID- 27397357 TI - 02-08 A randomized controlled trial of psychotherapeutic early intervention for borderline personality disorder. PMID- 27397359 TI - 03-01 Bipolar disorder - diagnostic and clinical perspectives. PMID- 27397358 TI - From Molecules to Man (CINP/ASPR Bipolar Disorder Symposium). PMID- 27397360 TI - 03-02 Imaging studies of bipolar disorder: Are we there yet? PMID- 27397361 TI - 03-03 The neurobiology of bipolar disorder. PMID- 27397363 TI - 03-05 Treatments and outcomes in bipolar disorder. PMID- 27397362 TI - 03-04 Genetic and genomic approaches to better understanding bipolar disorder. PMID- 27397364 TI - PTSD and Neuroimaging: Neural Correlates of Affective, Cognitive and Clinical Response. PMID- 27397365 TI - 04-01 Abnormal recruitment of brain networks during trauma-neutral verbal working memory processing in PTSD. PMID- 27397366 TI - 04-02 Topography of event-related potentials to visuoverbal working memory updating and target detection in PTSD. PMID- 27397367 TI - 04-03 The neural networks of inhibitory control in post-traumatic stress disorder. PMID- 27397368 TI - 04-04 Treatment response and post-traumatic stress disorder: neuroimaging findings. PMID- 27397369 TI - 04-05 Neural activity in dissociative and nondissociative PTSD: an fMRI analysis of conscious and nonconscious fear processing. PMID- 27397370 TI - Schizophrenia and Bipolar Disorder in the Real World - 'Best Buys and Best Bets'. PMID- 27397371 TI - 05-01 The Australian SCAP Study: real-world schizophrenia - outcomes and economics. PMID- 27397372 TI - 05-02 The Australian SCAP Study: real-world schizophrenia - economics. PMID- 27397373 TI - 05-03 Disease burden of bipolar and schizoaffective disorder in an Australian cohort. PMID- 27397374 TI - 05-04 Are the short-term cost savings and benefits of an early psychosis program maintained at 8-year follow-up? PMID- 27397375 TI - 05-05 Cost-effectiveness of a preventive intervention for young people at ultrahigh risk of developing psychosis. PMID- 27397376 TI - Psychopathologies of Social Cognition: Linking Neural, Cognitive and Clinical Perspectives. PMID- 27397377 TI - 06-01 Emotion regulation in affective and nonaffective psychoses. PMID- 27397378 TI - 06-02 Processing and responding to social stimuli in borderline personality disorder: a selective review. PMID- 27397379 TI - 06-03 What is the evidence that social cognition deficits in schizophrenia represent a vulnerability marker? PMID- 27397381 TI - 06-05 Theory of mind in Williams syndrome assessed using a nonverbal task. PMID- 27397380 TI - 06-04 Social cognition in nonforensic psychopathy: further evidence for a dissociation between intact 'theory of mind' and impaired emotion processing. PMID- 27397382 TI - Brain Stimulation Approaches in the Treatment of Depression. PMID- 27397383 TI - 07-01 ECT - future directions: a trial of the effectiveness and safety of four forms of ECT, bitemporal, bifrontal, right unilateral and right unilateral (ultrabrief pulsewidth). PMID- 27397385 TI - 07-03 Vagus nerve stimulation for treatment-resistant depression: utility and possible mechanisms of action. PMID- 27397384 TI - 07-02 TMS treatment for depression: overview of efficacy and report on a sham controlled trial of twice daily left prefrontal rTMS. PMID- 27397386 TI - 07-04 Direct current and deep brain stimulation with lessons from neurosurgery. PMID- 27397387 TI - Different Approaches to Endophenotypes in Schizophrenia. PMID- 27397388 TI - 08-01 Neurochemical endophenotypes of schizophrenia. PMID- 27397389 TI - 08-02 Identifying Disease-specific Protein Expression Patterns Within the Syndrome of Schizophrenia. PMID- 27397391 TI - 08-04 Endophenotypic biobehavioural markers for schizophrenia: how close are we to finding the Holy Grail? PMID- 27397390 TI - 08-03 From biological marker to endophenotype: the role of animal models. PMID- 27397393 TI - The Role of Apolipoprotein E in Neuropsychiatric Disorders. PMID- 27397392 TI - 08-05 'Kraepelinian' and 'Bleulerian' schizophrenia: a genetic dissection of a cognitive endophenotype. PMID- 27397394 TI - 09-01 Role of apolipoprotein E in Alzheimer's disease. PMID- 27397395 TI - 09-02 Interaction of apolipoprotein-E with ATP-binding cassette transporters: Impact on neuronal cholesterol homeostasis and amyloid-beta peptide generation. PMID- 27397396 TI - 09-03 The role of apolipoprotein E in the pathology of schizophrenia and bipolar disorder. PMID- 27397397 TI - 09-04 Plasma apolipoprotein E: roles and targets in schizophrenia and bipolar disorder. PMID- 27397398 TI - Identifying Gene-brain Markers of Cognition and Emotion: Implications for Psychiatric Disorders. PMID- 27397399 TI - 10-01 Understanding genotype-phenotype relationships using the Brain Resource International Database: Implications for psychiatric conditions. PMID- 27397400 TI - 10-02 The neurodevelopmental effects of apolipoprotein E alleles on brain function. PMID- 27397401 TI - 10-03 Identifying pathways to depressed mood and cognitive dysfunction: the BDNF Val66Met polymorphism and early life stress. PMID- 27397402 TI - 10-04 Identifying markers of negative mood: the gender-specific influence of COMT and MAO-A polymorphisms on emotion processing. PMID- 27397403 TI - 10-05 Genotypes and neural binding in negative affect: the contribution of genetic polymorphisms to 40 Hz gamma phase synchrony. PMID- 27397404 TI - 'Integrative Neuroscience' and Psychiatry: Identifying Cognitive, Affective and Brainwave Markers of Psychiatric Disorder. PMID- 27397405 TI - 11-01 Identifying cognitive, affective and neural synchrony markers which predict real-world functional outcome in first-episode schizophrenia: an integrative neuroscience approach. PMID- 27397406 TI - 11-02 Identifying affective markers within an integrative neuroscience model of depression. PMID- 27397407 TI - 11-03 Identifying cognitive and affective markers within an integrative neuroscience model of ADHD. PMID- 27397408 TI - 11-04 Identifying cognitive and affective markers within an integrative neuroscience model of Alzheimer's dementia. PMID- 27397409 TI - Differences between obese and non-obese drivers in preferred vehicle interior components setting and driving posture. AB - This study compared obese and non-obese drivers in the preferred seat and steering wheel setting and preferred driving posture. Twenty-one extremely obese and 23 non-obese drivers participated. Each participant determined the most preferred setting of the interior components using an adjustable vehicle mock-up; the preferred components setting and corresponding preferred driving posture were recorded. The participant groups exhibited significant differences in the preferred interior components setting. The obese group created larger steering wheel-seat space than the non-obese, with greater rearward seat displacement, more upright steering wheel angle and smaller steering wheel column displacement. It also exhibited more upright seatback angle deemed necessary for facilitating steering wheel reach with the increased steering wheel-seat distance. The between group differences in the preferred driving posture were less pronounced: no significant group mean angle differences were found except for the elbow joint angles. Also, the mean hip joint centre positions did not significantly differ. Practitioner Summary: To contribute to larger driver packaging, this study compared obese and non-obese drivers in the preferred vehicle interior components setting and driving posture. The obese group created significantly larger space between the steering wheel and seat than the non-obese, through interior components adjustments. The between-group postural differences were less pronounced. PMID- 27397410 TI - Iodine-catalysed regioselective thiolation of flavonoids using sulfonyl hydrazides as sulfenylation reagents. AB - Iodine-catalysed regioselective sulfenylation of flavonoid derivatives with sulfonyl hydrazides was developed. Various flavonoid thioethers were obtained in moderate to good yield. The thiolation could be conveniently directed to C-8 for flavone, flavonol, dihydroflavone, and isoflavone derivatives or to C-7 for aurone derivatives by employing the isopropyl ethers of flavonoids bearing free OH groups at the C-5 or C-4 positions. PMID- 27397411 TI - Importance of Unimolecular HO2 Elimination in the Heterogeneous OH Reaction of Highly Oxygenated Tartaric Acid Aerosol. AB - Oxygenated organic molecules are abundant in atmospheric aerosols and are transformed by oxidation reactions near the aerosol surface by gas-phase oxidants such as hydroxyl (OH) radicals. To gain better insights into how the structure of an organic molecule, particularly in the presence of hydroxyl groups, controls the heterogeneous reaction mechanisms of oxygenated organic compounds, this study investigates the OH-radical initiated oxidation of aqueous tartaric acid (C4H6O6) droplets using an aerosol flow tube reactor. The molecular composition of the aerosols before and after reaction is characterized by a soft atmospheric pressure ionization source (Direct Analysis in Real Time) coupled with a high resolution mass spectrometer. The aerosol mass spectra reveal that four major reaction products are formed: a single C4 functionalization product (C4H4O6) and three C3 fragmentation products (C3H4O4, C3H2O4, and C3H2O5). The C4 functionalization product does not appear to originate from peroxy radical self reactions but instead forms via an alpha-hydroxylperoxy radical produced by a hydrogen atom abstraction by OH at the tertiary carbon site. The proximity of a hydroxyl group to peroxy group enhances the unimolecular HO2 elimination from the alpha-hydroxylperoxy intermediate. This alcohol-to-ketone conversion yields 2 hydroxy-3-oxosuccinic acid (C4H4O6), the major reaction product. While in general, C-C bond scission reactions are expected to dominate the chemistry of organic compounds with high average carbon oxidation states (OSC), our results show that molecular structure can play a larger role in the heterogeneous transformation of tartaric acid (OSC = 1.5). These results are also compared with two structurally related dicarboxylic acids (succinic acid and 2,3 dimethylsuccinic acid) to elucidate how the identity and location of functional groups (methyl and hydroxyl groups) alter heterogeneous reaction mechanisms. PMID- 27397412 TI - Haemophagocytic lymphohistiocytosis presenting as neonatal liver failure: A case series. AB - BACKGROUND AND STUDY AIM: Haemophagocytic lymphohistiocytosis (HLH) is a life threatening clinical syndrome with liver involvement varying from mild dysfunction to severe fulminant failure. The aim of this study was to present a case series of four HLH patients presenting with acute liver failure (ALF) in the neonatal period. PATIENTS AND METHODS: All four patients were neonates at the onset of symptoms. They presented to Cairo University Pediatric Hospital with ALF; they underwent prompt investigations including determination of ferritin, fibrinogen, and triglyceride levels as part of our ALF workup. Further investigations were tailored according to the associated clinical features and the results of preliminary investigations. RESULTS: HLH was diagnosed according to HLH-2004 criteria. Three patients fulfilled at least five out of eight criteria. Fever, splenomegaly, elevated ferritin levels, and low fibrinogen levels were present in all patients. The fourth patient had a serum ferritin level >10,000ng/ml, favouring the diagnosis of HLH, despite fulfilling only four out of eight criteria. For three patients, positive consanguinity and previous sibling death were reported, suggesting a genetic aetiology of HLH. CONCLUSION: ALF can be the presenting feature of HLH; thus, a high index of suspicion is necessary. Fever is a hallmark, especially in neonates. Diagnosis is important for this potentially treatable condition. PMID- 27397413 TI - Non-invasive monitoring of spreading depression. AB - Spreading depression (SD), a slow propagating depolarization wave, plays an important role in pathophysiology of different neurological disorders. Yet, research into SD-related disorders has been hampered by the lack of non-invasive recording techniques of SD. Here we compared the manifestations of SD in continuous non-invasive electroencephalogram (EEG) recordings to invasive electrocorticographic (ECoG) recordings in order to obtain further insights into generator structures and electrogenic mechanisms of surface recording of SD. SD was induced by KCl application and simultaneous SD recordings were performed by scalp EEG as well as ECoG electrodes of somatosensory neocortex of rats using a novel homemade EEG amplifier, AgCl recording electrodes, and high chloride conductive gel. Different methods were used to analyze the data; including the spectrogram, bi-spectrogram, pattern distribution, relative spectrum power, and multivariable Gaussian fit analysis. The negative direct current (DC) shifts recorded by scalp electrodes exhibited a high homogeneity to those recorded by ECoG electrodes. Furthermore, this novel method of recording and analysis was able to separate SD recorded by scalp electrodes from non-neuronal DC shifts induced by other potential generators, such as the skin, muscles, arteries, dura, etc. These data suggest a novel application for continuous non-invasive monitoring of DC potential changes, such as SD. Non-invasive monitoring of SD would allow early intervention and improve outcome in SD-related neurological disorders. PMID- 27397414 TI - Sharps and Needlestick Injuries Among Medical Students, Surgical Residents, Faculty, and Operating Room Staff at a Single Academic Institution. AB - BACKGROUND: The hospital is a place of high risk for sharps and needlestick injuries (SNI) and such injuries are historically underreported. METHODS: This institutional review board approved study compares the incidence of SNI among all surgical personnel at a single academic institution via an anonymous electronic survey distributed to medical students, surgical residents, general surgery attendings, surgical technicians, and operating room nurses. RESULTS: The overall survey response rate was 37% (195/528). Among all respondents, 55% (107/195) had a history of a SNI in the workplace. The overall report rate following an initial SNI was 64%. Surgical staff reported SNIs more frequently, with an incidence rate ratio (IRR) of 1.33 (p = 0.085) when compared with attendings. When compared with surgical attendings, medical students (IRR of 2.86, p = 0.008) and residents (IRR of 2.21, p = 0.04) were more likely to cite fear as a reason for not reporting SNIs. Approximately 65% of respondents did not report their exposure either because of the time consuming process or the patient involved was perceived to be low-risk or both. CONCLUSIONS: The 2 most common reasons for not reporting SNIs at our institution are because of the inability to complete the time consuming reporting process and fear of embarrassment or punitive response because of admitting an injury. Further research is necessary to mitigate these factors. PMID- 27397415 TI - Noticeable Variations in the Educational Exposure During Residency in Danish Orthopedic Departments. AB - OBJECTIVE: The objective of the study was to examine the educational exposure during residency in Danish orthopedic departments. DESIGN: Questionnaire-based cross-sectional study. SETTING: Data were gathered from January 1, 2014 to April 30, 2014 through a nationwide web-based questionnaire containing 15 questions within the areas of workload, surgical procedures, outpatient clinic, and research activities. The residents targeted worked at small-to-large hospitals and in tertiary care centers. PARTICIPANTS: Every resident in Denmark (n = 163) with at least 3 active months at a department was included. Questionnaires with less than 80% completion were excluded. In total, 152 entries were registered. Among those, 27 did not meet the inclusion criteria and 29 were excluded, leaving 96 participants, representing 22 of 26 departments, for further analysis. RESULTS: The average number of operative procedures as primary surgeon was 16 (range: 8-35) per month. In all, 18 of 22 (81%) departments offered the possibility to participate in research facilitated by the department and 38 of 96 (40%) worked for free (an average of 10h a month [range: 3-60]) to increase the amount of surgical procedures. CONCLUSIONS: A large variation in the educational exposure was found among the Danish orthopedic departments. Numbers indicate that Danish residents, compared with their US counterparts, operate considerably less during residency. Most residents work overtime and many of them work for free to participate in more surgical procedures. PMID- 27397416 TI - Addressing Simulation Training. PMID- 27397417 TI - A patient-controlled functional electrical stimulation system for arm weight relief. AB - A patient-driven control strategy for Functional Electrical Stimulation (FES), which amplifies volitionally-initiated shoulder abductions, is proposed to improve stroke patients' rehabilitation. Based on the measured abduction angle, a FES-induced muscle recruitment is generated that yields a pre-specified percentage of this angle - yielding arm weight relief. To guarantee the correct recruitment also under fatigue and uncertain muscle activation we employ feedback control of the recruitment level determined by filtering the FES-evoked electromyogram. Filter parameters are user-optimized to obtain a linear relation between filter output and angle with a good signal-to-noise ratio. The auto-tuned recruitment controller (RC) was tested on five healthy subjects and compared to direct stimulation (DS) while muscle fatigue progressively occurred. Results showed a more linear relation between recruitment level and angle than between non-controlled stimulation intensity and angle (R2=0.93 vs. R2=0.79, angular range of 54 degrees ). After 6 min of stimulation, abduction decreased by 42% +/- 14 for DS and by 0% +/- 12 for RC, showing an effective compensation of fatigue. RC yielded significant smaller errors than DS in generating desired angles (0.23% +/- 5.9 vs. 14.6% +/- 9.7). When FES-induced arm weight support was provided, a mean reduction of the volitional effort (determined by Electromyography) of 78% was achieved compared to angular tracking without FES. First experiments with one acute stroke patient are also reported. PMID- 27397419 TI - Response to characterization of orbital masses by multiparametric MRI. PMID- 27397418 TI - Chronic tubulointerstitial nephropathy induced by glucosamine: a case report and literature review. AB - Glucosamine is a glycosylated amine and a slow-acting symptomatic treatment for osteoarthritis. Some experimental animal studies have shown that glucosamine can cause apoptosis in kidney tubular and mesangial cells as well as overexpression of transforming growth factor beta1 (TGF-beta1) and connective-tissue growth factor (CTGF), which are potent inducers of mesangial and interstitial tubulointerstitial fibrosis. We report the case of a 67-year-old patient who presented with non-proteinuric renal insufficiency and a reduction of the glomerularfiltration rate (GFR) from 86 to 46 mL/min within 3 months. A kidney biopsy showed noninflammatory 40 - 50% fibrosis of the renal cortex associated with acute tubular necrosis. The etiological investigation was negative apart from taking 1,200 mg of glucosamine daily for 3 years to treat osteoarthritic knee pain. Three weeks after stopping glucosamine, GFR increased from 47.5 to 60 mL/min. Reintroduction of glucosamine resulted in loss of kidney function after 3 weeks, with GFR reduced from 60 to 53 mL/ min. Thus, glucosamine was shown to cause renal toxicity. Referring to other reported cases, we conclude that toxicity is rare but may also be underreported. PMID- 27397420 TI - Chunking as the result of an efficiency computation trade-off. AB - How to move efficiently is an optimal control problem, whose computational complexity grows exponentially with the horizon of the planned trajectory. Breaking a compound movement into a series of chunks, each planned over a shorter horizon can thus reduce the overall computational complexity and associated costs while limiting the achievable efficiency. This trade-off suggests a cost effective learning strategy: to learn new movements we should start with many short chunks (to limit the cost of computation). As practice reduces the impediments to more complex computation, the chunking structure should evolve to allow progressively more efficient movements (to maximize efficiency). Here we show that monkeys learning a reaching sequence over an extended period of time adopt this strategy by performing movements that can be described as locally optimal trajectories. Chunking can thus be understood as a cost-effective strategy for producing and learning efficient movements. PMID- 27397421 TI - [The future of hospitals and the hospitals in the future]. AB - By the end of the 20th century the vertically organized hospitals formed into a closed hierarchical system, in which the healthcare supply significantly fragmented. The existing hospitals in the current organization are not prepared for the increase in longevity, nor for the high growth in the number of chronic and long-term illnesses and the multi-morbidity since they were not designed for extended carry treatments. The fast incorporation of high-tech and very expensive technologies into healthcare generates an economic crisis. Solving the supply and economic crisis at the same time cannot be achieved without changing the structure of hospitals. Future hospitals will be organized in a network, conducting special treatments according to disease profiles. According to present knowledge, this is the only structure that allows for economies in scale, the proper spending of the ever-shrinking resources, and to ensure the effective patient care required after the changing of disorder structures and patient corporate identities. Orv. Hetil., 2016, 157(28), 1099-1104. PMID- 27397422 TI - [Violent acts against health care providers]. AB - Violence against health care providers is getting more awareness nowadays. These are usually deliberate actions committed by patients or family members of them resulting in short and long term physical or psychological debilitating harm in the staff members. The causes of the violent acts are usually rooted in patient related factors, although some characteristics of the professionals and of the workplace may also play some role. The present article presents different definitions of violence and possible reasons for violence against health care providers based on relevant international and national literature. The paper discusses the different forms and frequency of violence, furthermore, details about the effects, consequences and some options for prevention in health care settings are also included. Orv. Hetil., 2016, 157(28), 1105-1109. PMID- 27397423 TI - [Oncologic aspects of Clostridium difficile]. AB - Clostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 degrees C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Orv. Hetil., 2016, 157(28), 1110-1116. PMID- 27397424 TI - [Latest international guidelines for screening, prevention and treatment of familial breast cancer - implications for the relevant practice in Hungary]. AB - INTRODUCTION: Screening, prevention and treatment of familial breast cancer require a multidisciplinary approach. New guidelines were published in the United Kingdom for the management of familial breast cancer. AIM: The authors summarise these new guidelines and analyse the relevant practice in Hungary. METHOD: Relevant guidelines of the National Institute for Health and Care Excellence and Familial Breast Cancer Report (NHS Scotland) are described. RESULTS: New guidelines will increase the number of genetic tests as well as genetic counselling. An increase in the number of breast magnetic resonance imaging is expected, too. Chemoprevention can be offered for individuals with medium risk and above. Promising trials are underway with platinum based chemotherapy and polyADP-ribose polimerase inhibitors for the systemic treatment of familial breast cancer. The increase in the number of genetic tests, counselling, and breast magnetic resonance imaging may have a significant impact on health care budget. CONCLUSIONS: These guidelines will change some aspects of the current management of familial breast cancer. Orv. Hetil., 2016, 157(28), 1117-1125. PMID- 27397426 TI - [Miscellaneous]. PMID- 27397425 TI - [Interdisciplinary rehabilitation in patients with ankylosing spondylitis]. AB - INTRODUCTION: Complex pulmonary assessment related to respiratory manifestation in patients with ankylosing spondylitis may contribute to adaptation of an appropriate rehabilitation program. AIM: To examine the relationship between lung function, exercise physiological variables and change in quality of life after rehabilitation in patients with ankylosing spondylitis. METHOD: 5 patients in Seyfried's Stage 2 and 11 patients in Stage 3 underwent spinal physiotherapy, ultrasound, massage and paraffin Pack, 15 times each, followed by a high intensity cycling 3 times a week for 8 weeks. The Bath Ankylosing Spondylitis Disease Activity and Bath Ankylosing Spondylitis Functional Indexes were recorded before and after rehabilitation. Lung function with exercise physiological variables were examined after rehabilitation. RESULTS: Both indexes showed a post treatment significant improvement compared to the initial scores (p<0.05). These functional indices correlated with lung function at rest and physiological variables during exercise (p<0.05). CONCLUSIONS: Based on this study, it is possible that an initial pulmonary assessment may serve to develop a more effective program for ankylosing spondylitis. Orv. Hetil., 2016, 157(28), 1126 1132. PMID- 27397427 TI - Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver. AB - We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats. Male Sprague-Dawley rats were fed with either regular or HF diet for 8 weeks. Rats fed with regular diet were treated with vehicle for further 4 weeks. HF fed rats were divided into 6 groups, namely, vehicle, celecoxib (30mg/kg/day), metformin (300mg/kg/day), metformin (150mg/kg/day), metformin (300mg/kg/day) with celecoxib (30mg/kg/day), and metformin (150mg/kg/day) with celecoxib (15mg/kg/day) for additional 4 weeks. Increased body weight in HF fed rats was significantly reduced by metformin alone and metformin combined with celecoxib. The increases in the HOMA-IR value and the area under the curve of glucose following an oral glucose tolerance test, systolic blood pressure, and adipocyte size were significantly diminished in treated rats, especially rats undergoing combined treatment. Treatments with either celecoxib or in combination with metformin resulted in a reduction in AT macrophage infiltration and decreases in levels of adipose tissue TNF-alpha, MCP 1, and leptin levels in high-fat (HF) fed rats. Furthermore, the elevated hepatic triglycerides content was significantly decreased in the combined treatment group compared to that of groups of celecoxib or metformin alone. Celecoxib exerts a synergistic beneficial effect with metformin on and obesity-associated metabolic and cardiovascular disorders in high-fat fed rats. PMID- 27397428 TI - PASS assisted prediction and pharmacological evaluation of hesperidin against scopolamine induced amnesia in mice. AB - Alzheimer's disease (AD) is a neurodegenerative disorder that leads to memory impairment. However, the exact etiology of AD is not clear but cholinergic dysfunction and oxidative stress are considered to play an important role in its pathogenesis. Because of this reason, antioxidant compounds are expected to play potential beneficial role in this disease. Among number of antioxidant compounds, hesperidin (HSD) was selected for this study on the basis of its reported antioxidant and neuroprotective effects. Moreover, it has shown higher probable activity value for scavenging free radical along with anti-dementia effects, predicted by PASS online computer program. Current study was designed to evaluate the nootropic and antioxidant effects of HSD. The different groups of animals received scopolamine (2mg/kg) along with co-treamtment of HSD (100, 200mg/kg) and donepezil HCl (3mg/kg) i.p. for consecutive 10 days. Behavioral tests were carried out, 30min after respective treatment on 2nd, 5th and 9th day for memory evaluation. On 10th day of treatment, the animals were sacrificed and the homogenates of brain hippocampus and cortex were used for biochemical estimation. Co-treatment with HSD at both doses significantly reversed the changes in memory and biochemical alterations, induced by scopolamine administration. It can be concluded that HSD has strong memory enhancing and anti-oxidant effects, therefore, it can be considered as a potential candidate for its further pharmacological evaluation for AD-induced dementia. PMID- 27397429 TI - Centhaquin attenuates hyperalgesia and non-evoked guarding in a rat model of postoperative pain primarily through alpha2B-adrenoceptors. AB - Centhaquin has been shown to produce antinociception in the mouse hot plate and tail flick assays through the opioid, the alpha2A and alpha2B adrenoceptors. Present study was conducted to determine the effects of centhaquin in a rat model of postoperative pain. Involvement of opioid, and adrenergic receptors was assessed by pretreating rats with antagonists at the opioid (naloxone), alpha2 (atipamezole) or alpha2B-(imiloxan) adrenergic receptors. Postoperative pain was induced by hind paw plantar incision in male Sprague Dawley rats. Antihyperalgesic effects were determined by measurement of paw withdrawal latencies and withdrawal force, using dynamic von Frey filaments; attenuation of non-evoked guarding was measured by assigning pain scores to spontaneous behaviors. Rotarod test was used to determine motor impairment. Animals received saline, centhaquin or antagonist plus centhaquin. Centhaquin produced dose dependent antihyperalgesic effect and attenuation of non-evoked guarding behavior, versus saline treated rats (P<0.05). Naloxone partially blocked while atipamezole and imiloxan significantly reversed centhaquin's antihyperalgesic effects (P<0.05). Attenuation of non-evoked guarding behavior was also blocked, but was not statistically significant. Imiloxan produced a greater block compared to atipamezole while naloxone had no significant effect. Rotarod testing indicated that centhaquin did not cause motor impairment. This is the first report demonstrating centhaquin antinociception in the rat postoperative pain model. Opioid, alpha2 adrenergic, and particularly alpha2B adrenergic receptors are involved in mediating antihyperalgesia while attenuation of nonevoked guarding is mediated by alpha2B/alpha2 adrenergic receptors. Centhaquin could be an effective non-sedating alternative in treating postoperative pain in ambulatory surgeries. PMID- 27397430 TI - Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes. AB - In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 MUMU with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300MUM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30MUM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30MUM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. PMID- 27397431 TI - Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3 dependent mechanisms. AB - Renal fibrosis, a common feature and leading cause for End Stage Renal Disease, still lacks effective therapy. In the current study, we detected and compared the anti-fibrotic effects of wogonin and wogonoside, two major components of Scutellaria baicalensis Georgi, in TGF-beta1-treated tubular epithelial cells of human and murine origins. Results consistently showed that compared with wogonoside, wogonin inhibits TGF-beta1-induced upregulated mRNA and protein levels of collagen I and alpha-SMA with more efficiency, which was further confirmed by the immunofluorescence results that wogonin decreased the percentage of collagen I and alpha-SMA positive cells in TGF-beta1-treated tubular epithelial cells. Mechanistically, wogonin mainly decreased Smad3 phosphorylation, but had marginal effect on non-canonical TGF-beta signaling pathways, such as p38 and ERK MAP Kinase. Furthermore, in the cells deficient for TGF-beta signaling or downstream Smad3, results demonstrated that even high concentration of wogonin failed to further decrease the level of collagen I and alpha-SMA, indicating the essential role of TGF-beta/Smad3 signaling inhibition in the therapeutic action of wogonin in TGF-beta1-stimulated tubular epithelial cells. Collectively, our results indicated that wogonin may be utilized as a potential anti-fibrotic Traditional Chinese Medicine monomer in the treatment of renal fibrosis. PMID- 27397432 TI - Two new quinones from the roots of Juglans mandshurica. AB - Two new quinones, 1-hydroxy-5-pentyl-anthraquinone (1) and 4-(5-hydroxy-1,4-dioxo 1,4-dihydro-naphthalen-2-ylamino)-butyric acid methyl ester (2), together with two known quinones, 5-hydroxy-2-(2-hydroxy-ethylamino)-(1,4) naphthoquinone (3) and juglone (4) were isolated from the roots of Juglans mandshurica (Juglandaceae). Their structures were elucidated on the basis of spectral data. Compound 3 was isolated from the Juglans genus for the first time. Compounds 1-4 exhibited significant cytotoxicity towards cultured MDA-MB231, HepG2 and SNU638 cells with IC50 values ranging from 4.46 to 88.47 MUM. PMID- 27397433 TI - Antibiotic Resistance: The Need For a Global Strategy. AB - The development of antibiotic resistance is a major problem for mankind and results in fatal consequences on a daily basis across the globe. There are a number of reasons for this situation including increasing globalization with worldwide travel, health tourism, over use and ineffective use (both in man and animals), and counterfeiting of the antimicrobial drug products we have available currently. Although there are huge economical, demographic, legal and logistic differences among the global communities, there are also differences regarding the best approach to dealing with antibiotic resistance. However, as resistant bacteria do not respect international borders, there is clearly a need for a global strategy to minimize the spread of antibiotic resistance, to optimize the use of antibiotics, and to facilitate the development of new and effective medications. This commentary provides an insight into the issues and some of the ongoing programs to ensure an effective treatment for the future. PMID- 27397434 TI - Dissolution Methods to Increasing Discriminatory Power of In Vitro Dissolution Testing for Ibuprofen Free Acid and Its Salts. AB - The predictive capacity of in vitro dissolution tests using the Biopharmaceutics Classification System (BCS)-based experimental setup to anticipate in vivo bioequivalence outcomes for BCS class 2 weak acids has been questioned. In this work, the effect of buffer concentration media was investigated as a possible approach to ensuring the discriminative capacity of the in vitro dissolution methods. The case example used to test this approach was ibuprofen, formulated as either the free acid or in various salt forms. By matching the concentration of buffers commonly used to prepare media which aim to simulate the intestinal conditions with that of bicarbonate buffer, which is the predominant buffer species in vivo, to arrive at the same surface pH (pH0), the discriminative power of the in vitro dissolution tests was improved. To simulate the in vivo results even better, a pretreatment at acidic pH was added to the dissolution test simulating the gastric conditions to create a 2-stage test. With the 2-stage test, it was possible to account for differences in disintegration in a more physiologically relevant way and thus to better reflect the in vivo performance of the various formulations. PMID- 27397435 TI - On the Thermal Stability of the Diethylcarbamazine-Fortified Table Salt Used in the Control of Lymphatic Filariasis. AB - Diethylcarbamazine, administered as a water-soluble citrate salt, has been used for more than 50 years as the first-line drug in the treatment of lymphatic filariasis. Mass drug administration programs have been successful in reducing microfilaremia and providing important collateral deworming benefits. One of these initiatives is based on the addition of diethylcarbamazine citrate to table salt. The fortified salt retaining the efficacy of the drug in reducing microfilaremia, but there is little information about its behavior above room temperature. In this study, the thermal stability of diethylcarbamazine, as a free base and a citrate salt, was investigated by differential scanning calorimetry and thermogravimetry under different conditions. Diethylcarbamazine does not release hazardous degradation substances above its melting point. It was also confirmed that this drug is stable at normal cooking temperatures, even when dry heat cooking methods, such as baking or grilling, are considered. However, if the drug is formulated as a salt, as in the case of the citrate, special attention needs to be given to the degradation substances of the counter ion. PMID- 27397436 TI - Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage. AB - MicroRNAs (miRNA) are short single-stranded RNA sequences that have a role in the post-transcriptional regulation of genes. The identification of tissue specific or enriched miRNAs has great potential as novel safety biomarkers. One longstanding goal is to associate the increase of miRNA in biofluids (e.g., plasma and urine) with tissue-specific damage. Next-generation sequencing (miR seq) was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (acetaminophen [APAP] or carbon tetrachloride [CCL4 ]). Analyses with traditional serum chemistry and histopathology confirmed that toxicant induced organ damage was specific. In animals treated with cisplatin, levels of five miRNAs were significantly altered in the kidney, 14 in plasma and six in urine. In APAP-treated animals, five miRNAs were altered in the liver, 74 in plasma and six in urine; for CCL4 the changes were five, 20 and 6, respectively. Cisplatin treatment caused an elevation of miR-378a in the urine, confirming the findings of other similar studies. There were 17 in common miRNAs elevated in the plasma after treatment with either APAP or CCL4 . Four of these (miR-122, -802, 31a and -365) are known to be enriched in the livers of rats. Interestingly, the increase of serum miR-802 in both hepatotoxicant treatments was comparable to that of the well-known liver damage marker miR-122. Taken together, comparative analysis of urine and plasma miRNAs demonstrated their utility as biomarkers of organ injury. Copyright (c) 2016 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID- 27397438 TI - Simulation in cardiac critical care: New times and new solutions. PMID- 27397439 TI - Dilemma with the route of venous access for hemodialysis catheter insertion in a patient with dilated ischemic cardiomyopathy treated by cardiac resynchronization therapy. AB - A 68 year old patient requiring urgent dialysis due to raising potassium was referred to our center. He had 3 indwelling catheters in his heart via right subclavian vein. His left subclavian and interngal jugular veins were thrombosed possibly due to earlier indwelling catheters. The dilemma was if right internal jugular venous route could be used for insertion of dialysis catheter. Under fluoroscopic guidance, right internal jugular vein was cannulated with the dialysis catheter without problems. This case is being presented to highlight the need for imaging both by ultrasound and radiography during the procedure. PMID- 27397440 TI - Should cerebral oximetry be used as routine monitoring for cardiovascular surgical cases? PMID- 27397441 TI - Effect of dexmedetomidine on diseased coronary vessel diameter and myocardial protection in percutaneous coronary interventional patients. AB - INTRODUCTION: Dexmedetomidine is an alpha-2 agonist used for conscious sedation. It has also been shown to have a myocardial protective effect in off-pump coronary artery bypass patients. The aim of the study was to assess the effect of dexmedetomidine for myocardial protection in percutaneous coronary interventional patients. METHODOLOGY: A total of 60 patients (group dexmedetomidine, n = 30 and group normal saline, n = 30) were enrolled in the study. Dexmedetomidine infusion (1 mcg/kg) over 15 min was given as a loading dose after coronary angiography in group dexmedetomidine (D) while normal saline was given in the control group (C) and later maintenance infusion was started at 0.5 mcg/kg/h in both the groups. Coronary vessel diameter was noted before (T0) and after (T1) loading dose of dexmedetomidine/saline in each group. Troponin T (Trop T) values were noted at baseline (T0), 6 h (T2), 12 h (T3) and 24 h (T4) after starting the loading dose. Hemodynamic variables (heart rate [HR] and blood pressure) were monitored at T0, T1, and at regular intervals till 2 h postprocedure. RESULTS: Coronary vessel diameter and HR significantly decreased in group D as compared to control group (P < 0.05) whereas the decrease in Trop T at 6 h, 12 h, and 24 h were not statistically significant between the two groups. CONCLUSION: Dexmedetomidine decreases the coronary vessel diameter, but maintains the myocardial oxygen demand-supply ratio by decreasing the HR. The decrease in Trop T is statistically insignificant at the doses used. PMID- 27397442 TI - Feasibility of measuring superior mesenteric artery blood flow during cardiac surgery under hypothermic cardiopulmonary bypass using transesophageal echocardiography: An observational study. AB - BACKGROUND: Abdominal complications being rare but results in high mortality, commonly due to splanchnic organ hypoperfusion during the perioperative period of cardiac surgery. There are no feasible methods to monitor intraoperative superior mesenteric artery blood flow (SMABF). Hence, the aim of this study was to evaluate the feasibility and to measure SMABF using transesophageal echocardiography (TEE) during cardiac surgery under hypothermic cardiopulmonary bypass (CPB). METHODOLOGY: Thirty-five patients undergoing elective cardiac surgery under CPB were enrolled. Heart rate, mean arterial pressure (MAP), cardiac output (CO), SMABF, superior mesenteric artery (SMA) diameter, superior mesentric artery blood flow over cardiac output (SMA/CO) ratio and arterial blood lactates were recorded at three time intervals. T0: before sternotomy, T1: 30 min after initiation of CPB and T2: after sternal closure. RESULTS: SMA was demonstrated in 32 patients. SMABF, SMA diameter, SMA/CO, MAP and CO-decreased significantly (P < 0.0001) between T0 and T1, increased significantly ( P <= 0.001) between T1 and T2 and no significant change (P > 0.05) between T0 and T2. Lactates increased progressively from T0 to T2. CONCLUSION: Study shows that there is decrease in SMABF during CPB and returns to baseline after CPB. Hence, it is feasible to measure SMABF using TEE in patients undergoing cardiac surgery under hypothermic CPB. TEE can be a promising tool in detecting and preventing splanchnic hypoperfusion during perioperative period. PMID- 27397443 TI - Comparison between noninvasive measurement of central venous pressure using near infrared spectroscopy with an invasive central venous pressure monitoring in cardiac surgical Intensive Care Unit. AB - INTRODUCTION: Central venous pressure (CVP) measurement is essential in the management of certain clinical situations, including cardiac failure, volume overload and sepsis. CVP measurement requires catheterization of the central vein which is invasive and may lead to complications. The aim of this study was to evaluate the accuracy of measurement of CVP using a new noninvasive method based on near infrared spectroscopy (NIRS) in a group of cardiac surgical Intensive Care Unit (ICU) patients. METHODOLOGY: Thirty patients in cardiac surgical ICU were enrolled in the study who had an in situ central venous catheter (CVC). Sixty measurements were recorded in 1 h for each patient. A total of 1800 values were compared between noninvasive CVP (CVPn) obtained from Mespere VENUS 2000 CVP system and invasive CVP (CVPi) obtained from CVC. RESULTS: Strong positive correlation was found between CVPi and CVPn (R = 0.9272, P < 0.0001). Linear regression equation - CVPi = 0.5404 + 0.8875 * CVPn (r2 = 0.86, P < 0.001), Bland Altman bias plots showed mean difference +/- standard deviation and limits of agreement: -0.31 +/- 1.36 and - 2.99 to + 2.37 (CVPi-CVPn). CONCLUSION: Noninvasive assessment of the CVP based on NIRS yields readings consistently close to those measured invasively. CVPn may be a clinically useful substitute for CVPi measurements with an advantage of being simple and continuous. It is a promising tool for early management of acute state wherein knowledge of CVP is helpful. PMID- 27397444 TI - Effect of Vitamin C on adrenal suppression by etomidate induction in patients undergoing cardiac surgery: A randomized controlled trial. AB - INTRODUCTION: Etomidate is usually preferred in the induction of cardiac compromised patients due to its relative cardiovascular stability. However, the use of this drug has been limited as etomidate induces suppression of cortisol biosynthesis as a result of blockade of 11-beta-hydroxylation in the adrenal gland, mediated by the imidazole radical of etomidate. This study was carried out to observe the effect of Vitamin C on adrenal suppression after etomidate induction in patients undergoing cardiac surgery. MATERIALS AND METHODS: A total of 78 patients were randomly distributed into two groups. Group-I received oral Vitamin C (500 mg) twice daily and Group-II received antacid tablet as placebo twice daily instead of Vitamin C for 7 consecutive days prior to surgery till morning of surgery. Patients of both the groups induced with etomidate (0.1-0.3 mg/kg). Blood cortisol was estimated at different points of time till 24 th postinduction hour/blood lactate, glucose, hemodynamic parameters, and perioperative outcomes were assessed. RESULTS: Data of seventy patients (n = 35 in each group) were finally analyzed. Cortisol level is statistically significantly higher in Group-I (69.51 +/- 7.65) as compared to Group-II (27.74 +/- 4.72) (P < 0.05) in the 1 st postinduction hour. In Group-II, cortisol was consistently lower for 1 st 24 postinduction hour. Total adrenaline requirement was statistically significantly high in Group-II. Time of extubation, length of Intensive Care Unit stay arrhythmia was similar in both the groups. CONCLUSION: Vitamin C effectively inhibits etomidate-induced adrenal suppression in cardiac patients, thereby etomidate can be used as a safe alternative for induction in cardiac surgery under cardiopulmonary bypass when pretreated with Vitamin C. PMID- 27397445 TI - Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation. AB - BACKGROUND: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. METHODS: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. RESULTS: Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. CONCLUSIONS: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost. PMID- 27397446 TI - Hemodynamic challenge to early mobilization after cardiac surgery: A pilot study. AB - BACKGROUND: Active mobilization is a key component in fast-track surgical strategies. Following major surgery, clinicians are often reluctant to mobilize patients arguing that circulatory homeostasis would be impaired as a result of myocardial stunning, fluid shift, and autonomic dysfunction. AIMS: We examined the feasibility and safety of a mobilization protocol 12-24 h after elective cardiac surgery. SETTING AND DESIGN: This observational study was performed in a tertiary nonacademic cardiovascular Intensive Care Unit. MATERIALS AND METHODS: Over a 6-month period, we prospectively evaluated the hemodynamic response to a two-staged mobilization procedure in 53 consecutive patients. Before, during, and after the mobilization, hemodynamics parameters were recorded, including the central venous oxygen saturation (ScvO 2 ), lactate concentrations, mean arterial pressure (MAP), heart rate (HR), right atrial pressure (RAP), and arterial oxygen saturation (SpO 2 ). Any adverse events were documented. RESULTS: All patients successfully completed the mobilization procedure. Compared with the supine position, mobilization induced significant increases in arterial lactate (34.6% [31.6%, 47.6%], P = 0.0022) along with reduction in RAP (-33% [-21%, -45%], P < 0.0001) and ScvO 2 (-7.4% [-5.9%, -9.9%], P = 0.0002), whereas HR and SpO 2 were unchanged. Eighteen patients (34%) presented a decrease in MAP > 10% and nine of them (17%) required treatment. Hypotensive patients experienced a greater decrease in ScvO 2 (-18 +/- 5% vs. -9 +/- 4%, P = 0.004) with similar changes in RAP and HR. All hemodynamic parameters, but arterial lactate, recovered baseline values after resuming the horizontal position. CONCLUSIONS: Early mobilization after cardiac surgery appears to be a safe procedure as far as it is performed under close hemodynamic and clinical monitoring in an intensive care setting. PMID- 27397447 TI - Anesthetic implications of subxiphoid coronary artery bypass surgery. AB - BACKGROUND: Minimal invasive surgeries are carried out to benefit the patient with less pain, blood loss, mechanical ventilation and hospital stay; a smaller scar is not the aim. Minimal invasive cardiac surgeries are carried out via small sternotomy, small thoracotomy and via robotic arms. Subxiphoid route is a novel method and avoids sternotomy. AIM: This case series is an attempt to understand the anesthetic modifications required. Secondly, whether it is feasible to carry out subxiphoid coronary artery bypass surgery. METHODS: Elective patients scheduled to undergo subxiphoid coronary artery bypass surgery were chosen. The surgeries were conducted under general anesthesia with left lung isolation via either endobronchial tube or bronchial blocker. RESULTS: We conducted ten (seven males and 3 females) coronary artery bypass graft surgeries via subxiphoid technique. The mean EuroSCORE was 1.7 and the mean ejection fraction was 53.6. Eight patients underwent surgery via endobronchial tube, while, in the remaining two lung isolation was obtained using bronchial blocker. Mean blood loss intraoperatively was 300 +/- 42 ml and postoperatively 2000 +/- 95 ml. The pain score on the postoperative day '0' was 4.3 +/- 0.6 and 2.3 +/- 0.7 on the day of discharge. Length of stay in the hospital was 4.8 +/- 0.9 days. There were no complications, blood transfusions, conversion to cardiopulmonary bypass. The modifications in the anesthetic and surgical techniques are, use of left lung isolation using either endobronchial tube or bronchial blocker, increased duration for conduit harvesting, grafting, requirement of transesophageal echocardiography monitoring in addition to hemodynamic monitoring. Other minor requirements are transcutaneous pacing and defibrillator pads, a wedge under the chest to 'lift' up the chest, sparing right femoral artery and vein (to serve as vascular access) for an unlikely event of conversion to cardiopulmonary bypass. Any anesthesiologist wishing to start this technique must be aware of these modifications. CONCLUSIONS: Subxiphoid route is safe to carry out coronary artery bypass graft surgery using the minimal invasive cardiac surgery. It is reproducible and has undeniable benefits. We plan to conduct such surgeries in awake patients under thoracic epidural anesthesia thus making it even less invasive and amenable for fast tracking. PMID- 27397448 TI - Short-term prognostic value of perioperative coronary sinus-derived-serum cardiac troponin-I, creatine kinase-MB, lactate, pyruvate, and lactate-pyruvate ratio in adult patients undergoing open heart surgery. AB - OBJECTIVES: To investigate the release pattern of different cardiac metabolites and biomarkers directly from the coronary sinus (CS) and to establish the diagnostic discrimination limits of each marker protein and metabolites to evaluate perioperative myocardial injury in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). PATIENTS AND METHODS: Sixty-eight patients undergoing first mitral and/or aortic valve replacements with/without coronary artery bypass grafting and Bentall procedure under CPB and blood cardioplegic arrest were studied. All cardiac metabolites and biomarkers were measured in serial CS-derived blood samples at pre-CPB, immediate post aortic declamping, 10 minutes post-CPB and 12 hrs post-CPB. RESULTS: Receiver operating characteristic curve analysis of cardiac biomarkers indicated lactate-pyruvate ratio as the superior diagnostic discriminator of myocardial injury with an optimal "cut-off" value >10.8 immediately after aortic declamping (AUC, 0.92; 95% CI: 0.85-0.98). Lactate was the second best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >2mmol/l at immediately after aortic declamping (AUC, 0.89; 95% CI: 0.80-0.96). Cardiac troponin-I was the third best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >2.1ng/ml at immediately after aortic declamping (AUC, 0.88; 95% CI: 0.80-0.95). Creatine kinase-MB was the fourth best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >58 log units/ml prior to decanulation (AUC, 0.85; 95% CI: 0.78-0.94). CONCLUSIONS: Measurable cardiac damage exists in all patients undergoing cardiac surgery under cardioplegic arrest. The degree of myocardial injury is more in patients with poor ventricular function and those requiring longer aortic clamp time. CS-derived lactate-pyruvate ratio, lactate, cTn-I served as superior diagnostic discriminators of peri-operative myocardial damage. PMID- 27397449 TI - Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest. AB - OBJECTIVE: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO 3 ). The purpose of this study was to determine the relationships between total NaHCO 3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS). METHODS: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO 3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes. RESULTS: Seventy five patients (86%) received NaHCO 3 . Total NaHCO 3 dose averaged 136 +/- 112 mEq (range: 0.0-535 mEq) per patient. Total NaHCO 3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = -0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium >= 150 mEq/L. Total NaHCO 3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. CONCLUSION: Routine administration of NaHCO 3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO 3 was a function of the severity and duration of metabolic acidosis. NaHCO 3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO 3 dose administered was unrelated to short-term clinical outcomes. PMID- 27397450 TI - Conscious sedation using dexmedetomidine for percutaneous transcatheter closure of atrial septal defects: A single center experience. AB - OBJECTIVE: The aim of this study is to determine safety and feasibility of conscious sedation using dexmedetomidine for transcatheter atrial septal defect (ASD) device closure. MATERIAL AND METHODS: A retrospective institutional review of transcatheter ASD device closure without endotracheal intubation over 18 months. The protocol included topical oropharyngeal anesthesia using lignocaine followed by dexmedetomidine bolus 1 MUg/kg intravenously over 10 min and maintenance dose 0.2-0.7 MUg/kg/h. Ramsay sedation score 2-3 was maintained. Patients were analyzed regarding demographic profile, device size, procedure time, anesthesia time, recovery time, hospital stay, and any hemodynamic or procedural complications. RESULTS: A total of 43 patients with mean age 31.56 +/- 13.74 years (range: 12-56 years) were analyzed. Mean anesthesia duration was 71.75 + 21.08 min. Mean recovery time was 7.6 +/- 3.01 min. 16 females and one male patient required additional propofol with a mean dose of 30.8 +/- 10.49 mg. No hemodynamic instability was noted. No patient required general anesthesia with endotracheal intubation. The procedure was successful in 93.02% of patients. Four patients developed atrial fibrillation. All patients were satisfied. CONCLUSION: Conscious sedation using dexmedetomidine is a safe and effective anesthetic technique for percutaneous ASD closure. PMID- 27397451 TI - Comparison of speed of inhalational induction in children with and without congenital heart disease. AB - BACKGROUND: Conduct of stable inhalational anesthetic induction in children with congenital heart disease (CHD) presents special challenges. It requires in-depth understanding of the effect of congenital shunt lesions on the uptake, delivery, and equilibration of anesthetic drugs. Intracardiac shunts can alter the induction time and if delivery of anesthetic agent is not carefully titrated, can lead to overdosing and undesirable myocardial depression. AIMS: To study the effect of congenital shunt lesions on the speed of inhalational induction and also the impact of inhalational induction on hemodynamics in the presence of congenital shunt lesions. SETTING: Tertiary care hospital. DESIGN: A prospective, single-center clinical study. MATERIALS AND METHODS: Ninety-three pediatric patients undergoing elective surgery were segregated into three equal groups, namely, Group 1: no CHD, Group 2: acyanotic CHD, and Group 3: cyanotic CHD. General anesthesia was induced with 8% sevoflurane in 6 L/min air-oxygen. The time to induction was noted at loss of eyelash reflex and decrease in bispectral index (BIS) value below 60. End-tidal sevoflurane concentration, minimum alveolar concentration, and BIS were recorded at 15 s intervals for the 1 st min followed by 30 s interval for another 1 min during induction. Hemodynamic data were recorded before and after induction. RESULTS: Patients in Group 3 had significantly prolonged induction time (99 +/- 12.3 s; P < 0.001), almost twice that of the patients in other two groups (51 +/- 11.3 s in Group 1 and 53 +/- 12.0 s in Group 2). Hypotension occurred after induction in Group 1. No other adverse hemodynamic perturbations were observed. CONCLUSION: The time to inhalational induction of anesthesia is significantly prolonged in patients with right-to-left shunt, compared to patients without CHD or those with left-to-right shunt, in whom it is similar. Sevoflurane is safe and maintains stable hemodynamics in the presence of CHD. PMID- 27397452 TI - Intraoperative conversion to on-pump coronary artery bypass grafting is independently associated with higher mortality in patients undergoing off-pump coronary artery bypass grafting: A propensity-matched analysis. AB - CONTEXT: One of the main limitations of off-pump coronary artery bypass grafting (OPCAB) is the occasional need for intraoperative conversion (IOC) to on-pump coronary artery bypass grafting. IOC is associated with a significantly increased risk of mortality and postoperative morbidity. The impact of IOC on outcome cannot be assessed by a randomized control design. AIMS: The objective of this study was to analyze the incidence, risk factors, and impact of IOC on the outcome in patients undergoing OPCAB. SETTINGS AND DESIGN: Three tertiary care level hospitals; retrospective observational study. SUBJECTS AND METHODS: This retrospective observational study included 1971 consecutive patients undergoing OPCAB from January 2012 to October 2015 at three tertiary care level hospitals by four surgeons. The incidence, patient characteristics, cause of IOC, and its impact on outcome were studied. STATISTICAL ANALYSIS USED: The cohort was divided into two groups according to IOC. Univariate logistic regression was performed to describe the predictors of IOC. Variables that were found to be significant in univariate analysis were introduced into multivariate model, and adjusted odds ratio (OR) was calculated. To further assess the independent effect of IOC on mortality, propensity score matching with a 5:1 ratio of non-IOC to IOC was performed. RESULTS: The overall all-cause in-hospital mortality was 2.6%. IOC was needed in 128 (6.49%) patients. The mortality in the IOC group was significantly higher than non-IOC group (21 of 128 [16.4%] vs. 31 of 1843 [1.7%], P = 0.0001). The most common cause for IOC was hemodynamic disturbances during grafting to the obtuse marginal artery (51/128; 40%). On multivariate logistic regression analysis, left main disease, pulmonary hypertension, and mitral regurgitation independently predicted IOC. We obtained a propensity-matched sample of 692 patients (No IOC 570; IOC 122), and IOC had OR of 16.26 (confidence interval 6.3 41; P < 0.0001) for mortality in matched population. CONCLUSIONS: Emergency IOC increases odds for mortality by 16-fold. Hence, identification of patients at higher risk of IOC may improve the outcome. PMID- 27397453 TI - Novel no touch technique of saphenous vein harvesting: Is great graft patency rate provided? AB - Coronary artery bypass grafting surgery effectively relieves signs and symptoms of myocardial ischemia. The left internal thoracic artery (LITA) graft is the gold standard having 90-95% patency rate at 10 years, whereas only 50% of saphenous vein (SV) grafts are patent at 10 years. However, there is a novel "no touch" technique in order to harvest an SV complete with its cushion of surrounding tissue, thus maintaining its endothelium-intact. Significantly superior short- and long-term graft patency rates comparable to LITA grafts can be achieved. Consequently, the SV may be revived as an important conduit in coronary artery bypass surgery. PMID- 27397454 TI - Anesthetic challenges in minimally invasive cardiac surgery: Are we moving in a right direction? AB - Continuously growing patient's demand, technological innovation, and surgical expertise have led to the widespread popularity of minimally invasive cardiac surgery (MICS). Patient's demand is being driven by less surgical trauma, reduced scarring, lesser pain, substantially lesser duration of hospital stay, and early return to normal activity. In addition, MICS decreases the incidence of postoperative respiratory dysfunction, chronic pain, chest instability, deep sternal wound infection, bleeding, and atrial fibrillation. Widespread media coverage, competition among surgeons and hospitals, and their associated brand values have further contributed in raising awareness among patients. In this process, surgeons and anesthesiologist have moved from the comfort of traditional wide incision surgeries to more challenging and intensively skilled MICS. A wide variety of cardiac lesions, techniques, and approaches coupled with a significant learning curve have made the anesthesiologist's job a challenging one. Anesthesiologists facilitate in providing optimal surgical settings beginning with lung isolation, confirmation of diagnosis, cannula placement, and cardioplegia delivery. However, the concern remains and it mainly relates to patient safety, prolonged intraoperative duration, and reduced surgical exposure leading to suboptimal treatment. The risk of neurological complications, aortic injury, phrenic nerve palsy, and peripheral vascular thromboembolism can be reduced by proper preoperative evaluation and patient selection. Nevertheless, advancement in surgical instruments, perfusion practices, increasing use of transesophageal echocardiography, and accumulating experience of surgeons and anesthesiologist have somewhat helped in amelioration of these valid concerns. A patient-centric approach and clear communication between the surgeon, anesthesiologist, and perfusionist are vital for the success of MICS. PMID- 27397455 TI - Simulation for transthoracic echocardiography of aortic valve. AB - Simulation allows interactive transthoracic echocardiography (TTE) learning using a virtual three-dimensional model of the heart and may aid in the acquisition of the cognitive and technical skills needed to perform TTE. The ability to link probe manipulation, cardiac anatomy, and echocardiographic images using a simulator has been shown to be an effective model for training anesthesiology residents in transesophageal echocardiography. A proposed alternative to real time reality patient-based learning is simulation-based training that allows anesthesiologists to learn complex concepts and procedures, especially for specific structures such as aortic valve. PMID- 27397456 TI - Simulation in pediatrics: Is it about time? AB - Pediatrics is a challenging field where "Time is Essence" and the interplay of time-bound dynamics has a huge influence on the outcomes, particularly in an acutely ill child. In this context, simulation based training appears to play a major role in training young Paediatricians to develop critical decision making skills and learning in a risk-free environment. In present times and in future, it is expected that simulation is used by practically every healthcare provider at some or multiple points in the training and certification process. PMID- 27397457 TI - Simulation-based transthoracic echocardiography: "An anesthesiologist's perspective". AB - With the growing requirement of echocardiography in the perioperative management, the anesthesiologists need to be well trained in transthoracic echocardiography (TTE). Lack of formal, structured teaching program precludes the same. The present article reviews the expanding domain of TTE, simulation-based TTE training, the advancements, current limitations, and the importance of simulation based training for the anesthesiologists. PMID- 27397458 TI - Simulation in coagulation testing using rotational thromboelastometry: A fast emerging, reliable point of care technique. AB - Computer simulations can come in handy to train medical personnel with necessary skills to face the clinical scenarios involving various coagulopathies. Now a days, point of care (POC) devices such as thromboelastography, Sonoclot analyzer and newly approved rotational thromboelastometry (ROTEM) with faster results to assess coagulopathies are available on bedside of patients. ROTEM is emerging as a quick, portable, and well-validated device to evaluate coagulopathy in critical care and perioperative setup. A novel platelet-aggregometry integrated module enables simultaneous analysis of platelets as well as coagulation tests on the same screen. The entire gamut of POC signature curves obtained with different coagulation defects can be learned with graphical simulations. These simulations can be a valuable strategy to elucidate latent conditions, for which simulation interventions can then be designed to mimic different clinical scenarios. PMID- 27397459 TI - Simulation in cardiac catheterization laboratory: Need of the hour to improve the clinical skills. AB - Simulation is an effective teaching tool to decrease the learning curve for novices without compromising patient safety. Simulation helps interventionalist in mentally translating a two dimentional, black and white image into a usable three dimentional model. It also bridges the gap in training diverse team members on new procedures and products. All simulators have collision detection, i.e., virtual contact forces generated from collision which updates haptic output with new calculations. PMID- 27397460 TI - Transesophageal echocardiography for minimally invasive cardiac surgery-atrial septal defect closure. PMID- 27397461 TI - Simulation in thromboelastography: Platelet mapping assay (Part - I). PMID- 27397462 TI - Redo cardiac valve surgery and severe kyphoscoliosis: Anesthetic challenges. PMID- 27397463 TI - High cardiac output by Swan-Ganz catheter after repair of ventricular septal rupture-patch dehiscence or false overestimation? PMID- 27397464 TI - Simulation in critical care. PMID- 27397465 TI - Role of simulation in hemodynamic monitoring in cardiac surgery. PMID- 27397466 TI - Selective lobar blockade in minimally invasive coronary artery bypass grafting: A technical advantage in patients with low respiratory reserve that precludes one lung ventilation. AB - Minimally invasive cardiac surgery/coronary artery bypass grafting (MICS CABG) is performed through a small 2 inch left thoracotomy incision. Lung isolation is must during MICS CABG. Oxygenation with one-lung ventilation can be difficult, especially during supine position. We report a case of a 53-year-old male patient who underwent MICS CABG with the selective lobar blockade. PMID- 27397467 TI - Intercostal drainage tube or intracardiac drainage tube? AB - Although insertion of chest drain tubes is a common medical practice, there are risks associated with this procedure, especially when inexperienced physicians perform it. Wrong insertion of the tube has been known to cause morbidity and occasional mortality. We report a case where the left ventricle was accidentally punctured leading to near-exsanguination. This report is to highlight the need for experienced physicians to supervise the procedure and train the younger physician in the safe performance of the procedure. PMID- 27397468 TI - Undiagnosed aortic dissection in patient with intra-aortic balloon pump. AB - 60 years old lady presented with chest pain and was admitted in local hospital. Electrocardiogram was suggestive of anterior myocardial ischemia. Patient underwent coronary angiography which revealed severe triple vessles coronary artery disease. As patient was hemodynamically unstable and in cardiogenic shock, intraaortic balloon pump was inserted .IABP augmented diastolic blood pressure was less than unassisted systolic blood pressure despite setting maximum augmentation on IABP machine. PMID- 27397469 TI - Infective endocarditis of main pulmonary artery in tetralogy of Fallot: "Transesophageal echocardiography adds lease of life". AB - Infective endocarditis is a rare occurrence in the main pulmonary artery trunk and even rarer in tetralogy of Fallot. PMID- 27397470 TI - Iatrogenic dissection of the descending aorta: Conservative or endovascular treatment? AB - Transcatheter aortic valve implantation (TAVI) is without any doubt a standard technique and the treatment of choice of severe aortic valve stenosis (AVS) in very high-operative risk patients. However, a number of complications may occur and has been described. Improper valve position, valve migration, paravalvular regurgitation, conduction disturbances, stroke and aortic dissection have been succeeded despite the perfection of the technique. For anyone of the complications above described, a solution may be invented. We present an interesting case of an 81-year-old woman with severe AVS treated through TAVI due to very high operative risk. This female, 12 days later presented with thoracic pain and shortness of breath and through the computed tomography of the chest performed was diagnosed a dissection of the descending aorta. She successfully underwent on thoracic endovascular aortic repair. In this report, we refer the bibliographic data and we discuss the treatment options in these cases. PMID- 27397471 TI - Cetrimide-chlorhexidine-induced multiorgan failure in surgery of pulmonary hydatid cyst. AB - Savlon (0.5% cetrimide/0.05% chlorhexidine) is used as a scolicidal during surgery of hydatid cysts. It is considered a safe and effective agent. However, there are no recommendations for the appropriate concentration or dosage of these agents. Previously reported to cause severe metabolic acidosis, its effects on the pulmonary system have not been explored. We present a case of acute lung injury and respiratory distress along with acute cardiopulmonary distress, severe metabolic acidosis, and renal failure following its use during surgical removal of pulmonary hydatid cyst. The agent may act as a chemical sclerosant causing pulmonary parenchymal damage through bronchial openings present in the pericyst. Till safe dose limits are known, use of this agent should be limited, especially in large or multiple cyst surgery. PMID- 27397472 TI - Bidirectional Glenn with interruption of antegrade pulmonary blood flow: Which is the preferred option: Ligation or division of the pulmonary artery? AB - We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting. PMID- 27397473 TI - Perioperative challenges in management of a deaf and dumb patient posted for high risk cardiac surgery. AB - Perioperative management of deaf and dumb patients can be a challenging task. For smooth postoperative recovery, proper care should begin in the preoperative period. Understanding the patients' needs and training him to follow the instructions requires to involve a communication specialist. Judicious use of sedatives and analgesics is essential to keep the patient pain-free and comfortable. Postoperatively, the patient should be kept awake, enough to understand the internal need of the body and to make a meaningful response to external stimuli. Adequate preoperative planning and coordinated team efforts with involvement of specialists can help in delivering better postoperative care. PMID- 27397474 TI - Vascular airway compression management in a case of aortic arch and descending thoracic aortic aneurysm. AB - Airway compression due to distal aortic arch and descending aortic aneurysm repair has been documented. This case of tracheal and left main stem bronchus compression due to aortic aneurysm occurred in a 42-year-old man. The airway compression poses a challenge for the anesthesiologist in airway management during aortic aneurysm repair surgery. The fiber-optic bronchoscope is very helpful in decision-making both preoperatively and postoperatively in such cases. We report a case of airway compression in a 42-year-old patient who underwent elective distal aortic arch and descending aortic aneurysm repair. PMID- 27397475 TI - Infantile Hemangiomas of the Lip: Patterns, Outcomes, and Implications. AB - BACKGROUND: Infantile hemangiomas of the lip are potentially problematic because of high visibility and risk of disfigurement and ulceration. This study examined sizes, patterns, and locations of lip hemangiomas, their prognostic value, and their implications in hemangioma pathogenesis. METHODS: Records of 106 patients seen for lip hemangiomas from 2006 to 2013 at Nationwide Children's Hospital were reviewed. Localized hemangiomas were mapped to a location on the lip based on their focus. Size, location, and morphology were assessed with regard to outcome. Poor outcomes were considered to be marked anatomic deformity, scarring, functional complications, and ulceration. RESULTS: Of 72 untreated hemangiomas with discernible outcomes, 92% of segmental lip hemangiomas were associated with poor outcomes, as opposed to 32% of localized hemangiomas (p < 0.001). Localized lip hemangiomas originated from six distinct locations. Localized untreated hemangiomas with poor outcomes were, on average, approximately 2.36 cm(2) larger (95% confidence interval 1.47, 3.25) than those that resolved favorably (p < 0.001); 52% of upper lip untreated hemangiomas and 6% of lower lip hemangiomas had poor outcomes (p = 0.001), and 61% of untreated localized hemangiomas involving the vermilion border and 25% of those that did not had poor outcomes (p = 0.01). Hemangiomas that received early medical or surgical intervention were less likely to have poor outcomes than untreated hemangiomas (p = 0.03). CONCLUSIONS: Localized lip hemangiomas occur in distinct locations on the lip that are not random and appear to reflect known models of facial development. Segmental morphology is associated with poor outcomes. In localized hemangiomas, the upper lip is associated with more problematic outcomes than the lower lip. Large size and involvement of the vermilion border are also valuable prognostic indicators associated with poor outcomes. Early intervention in lip hemangiomas is associated with better outcomes. PMID- 27397476 TI - Scorpion Toxin Polyptides as Therapeutic Agents: An Overview. AB - Scorpions are distributed throughout the world and numerous biological molecules are found in their venom most importantly peptide toxins. These toxins modulate the ion channels either by blocking the pore of the channel or by altering the voltage gating. Molecules which block the pores have been useful in deciphering the structure of the ion channels. Many scorpion toxins have already been used for probing the voltage gated sodium channels and studying their activation and inactivation processes. The specialty of scorpion toxins is to discriminate between vertebrate and invertebrate channels which have led them to applications as pharmacological tools. Most of the scorpion toxin polypeptides were isolated, characterized and were shown to possess vital properties useful in the field of medicine. For instance, they show therapeutic properties such as antimicrobial activity, anticancer activity, used to treat autoimmune diseases and cardiovascular effects. Although the scorpion toxins exhibited good therapeutic effects in vitro and in vivo, no one has reached the market with success up to date. In this mini-review, the scorpion polypeptides, their interactions with ion channels and their uses as therapeutic agents are discussed. PMID- 27397477 TI - Identifying Small Coronary Calcification in Non-Contrast 0.5-mm Slice Reconstruction to Diagnose Coronary Artery Disease in Patients with a Conventional Zero Coronary Artery Calcium Score. AB - AIMS: In a new-generation computed tomography (CT) scanner, coronary artery calcium (CAC) scores were measured using 3.0-mm slice reconstruction images originally acquired with 0.5 mm thickness scans in a single beat. This study investigated the usefulness of thin-slice (0.5 mm) reconstruction for identifying small calcifications in coronary arteries and evaluated the association with coronary plaques and stenosis compared to conventional 3.0-mm reconstruction images. METHODS: We evaluated 132 patients with zero CAC scores in conventional 3.0-mm Agatston method using a 320-slice CT. Then, 0.5-mm slice reconstruction was performed to identify small calcifications. The presence of stenosis and coronary plaques was assessed using coronary CT angiography. RESULTS: In total, 22 small calcifications were identified in 18 patients. There were 28 (21%) patients with any (>= 25%) stenosis (34 lesions). Forty-seven coronary plaques were found in 33 patients (25%), including 7 calcified plaques in 7 patients (5%), 34 noncalcified plaques in 27 patients (20%), and 6 partially calcified plaques in 5 patients (4%). Patients with small calcifications had a significantly higher prevalence of noncalcified or partially calcified plaques (83% vs 14%; p<0.001) and obstructive stenosis (33% vs 5.2%; p<0.001) compared to those without small calcifications. The addition of small calcifications to the coronary risk factors when diagnosing stenosis significantly improved the diagnostic value. CONCLUSION: Small calcifications detected by thin-slice 0.5-mm reconstruction are useful for distinguishing coronary atherosclerotic lesions in patients with zero CAC scores from conventional CT reconstruction. PMID- 27397478 TI - Are Patients with Low Non-HDL Cholesterol "Non-responders" to Statin Therapy on Coronary Plaque Regression? PMID- 27397481 TI - SCLC-State of the Art and What Does the Future Have in Store? AB - Worldwide, the total number of diagnosed lung cancer cases amounts to 1.8 million every year. Small-cell lung cancer (SCLC) accounts for about 15% to 17% of all diagnosed lung cancers. Despite all progress made in the field of non-small-cell lung cancer, the prognosis and therapeutic options in SCLC are still limited. The resistance of SCLC to conventional therapy as well as its high recurrence rate can be attributed to the heterogeneous genetic structure of SCLC; however, a targeted therapy approach to SCLC may build on this very heterogeneous genetic structure. SCLC is by now a well-characterized cancer with various genetic alterations; for example, mutations in tumor suppressor genes TP53 and RB1, alterations in chromosome 3p, JAK2, FGFR1, and MYC genes were discovered. Based on these findings, various treatment options (eg, aurora kinase inhibitors, PARP inhibition, immune checkpoint inhibition and vaccine therapy) are currently evaluated with the goal of determining their clinical effectiveness. In this article, we review the existing knowledge of SCLC genetics and the current treatment standards and highlight new approaches of immunotherapy and other targeted therapies, which may yield new treatment options and improve the outcome of patients with SCLC. PMID- 27397480 TI - A systematic review of factors affecting intended and actual adherence with antiviral medication as treatment or prophylaxis in seasonal and pandemic flu. AB - The aim of this review was to identify factors predicting actual or intended adherence to antivirals as treatment or prophylaxis for influenza. Literature from inception to March 2015 was systematically reviewed to find studies reporting predictors of adherence to antivirals and self-reported reasons for non adherence to antivirals. Twenty-six studies were included in the review; twenty identified through the literature search and six through other means. Of these studies, 18 assessed predictors of actual adherence to antivirals, whereas eight assessed predictors of intended adherence. The most commonly found predictor of, and self-reported reason for, non-adherence was the occurrence of side effects. Other predictors include perceptions surrounding self-efficacy, response efficacy and perceived personal consequences as well as social influences of others' experiences of taking antivirals. Predictors identified in this review can be used to help inform communications to increase adherence to antivirals in both seasonal and pandemic influenza. PMID- 27397479 TI - Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities. AB - Given the importance of microRNAs (miRNAs) in modulating brain functions and their implications in neurocognitive disorders there are currently significant efforts devoted in the field of miRNA-based therapeutics to correct and/or to treat these brain diseases. The observation that miRNA 29a/b-1 cluster, miRNA 10b and miRNA 7, for instance, are frequently deregulated in the brains of patients with neurocognitive diseases and in animal models of Alzheimer, Huntington's and Parkinson's diseases, suggest that correction of miRNA expression using agonist or antagonist miRNA oligonucleotides might be a promising approach to correct or even to cure such diseases. The encouraging results from recent clinical trials allow envisioning that pharmacological approaches based on miRNAs might, in a near future, reach the requirements for successful therapeutic outcomes and will improve the healthcare of patients with brain injuries or disorders. This review will focus on the current strategies used to modulate pharmacological function of miRNA using chemically modified oligonucleotides. We will then review the recent literature on strategies to improve nucleic acid delivery across the blood-brain barrier which remains a severe obstacle to the widespread application of miRNA therapeutics to treat brain diseases. Finally, we provide a state-of-art of current preclinical research performed in animal models for the treatment of neurocognitive disorders using miRNA as therapeutic agents and discuss future developments of miRNA therapeutics. PMID- 27397483 TI - Foreword and Committee. PMID- 27397484 TI - Proceedings of the 31st Conference of the European Association of Veterinary Anatomists, Vienna, Austria, July 27-30 2016. PMID- 27397482 TI - Monitoring and Characterization of Circulating Tumor Cells (CTCs) in a Patient With EML4-ALK-Positive Non-Small Cell Lung Cancer (NSCLC). PMID- 27397485 TI - Primary focal prostate radiotherapy: Do all patients really need whole-prostate irradiation? AB - OBJECTIVES: To review the available data about focal primary partial prostate irradiation (focal radiotherapy, FRT) for early prostate cancer. METHODS: INCLUSION CRITERIA: Medline search for English language full paper on primary FRT for early prostate cancer including review articles, planning studies or patient series (clinical outcome available) published before May 31, 2015. RESULTS: 22 papers have been found: 11 review articles, 4 planning studies and 7 patient series. Eleven review articles were dedicated to all types of focal therapy including FRT and 2 to FRT only. All planning studies included brachytherapy and showed excellent organ-at-risk sparing. Patient series included together 715 patients (99% treated with brachytherapy) and showed promising tumour control in low-risk cancer. In intermediate-risk tumours, FRT might be suboptimal. CONCLUSIONS: Primary FRT is feasible in early prostate cancer. As any other focal therapy, FRT remains investigational until numerous questions are answered. PMID- 27397486 TI - Safety of anticoagulation in the treatment of venous thromboembolism in patients with haematological malignancies and thrombocytopenia: Report of 5 cases and literature review. AB - Venous thromboembolism (VTE) is relatively common among patients with haematological malignancies. Management is challenging because many of these patients are also thrombocytopenic and at increased risk of bleeding. Current recommendations regarding the treatment of VTE in thrombocytopenic patients with haematological malignancies are limited as there only few studies evaluating the safety and efficacy of anticoagulation in this population of patient. A literature review on the safety of antithrombotic therapy for treatment or prophylaxis of VTE in patients with haematological malignancies was undertaken. This includes a report on 5 patients with haematological malignancies at our institute who received enoxaparin for treatment of VTE while thrombocytopenic. Unlike previous case series which showed that the use of LMWH (low molecular weight heparin) is safe in this group of patients, major bleeding occurred in 2 patients, and was fatal in one case. More studies are required to evaluate the risk factors and safety of anticoagulation in these patients. PMID- 27397487 TI - The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice. AB - Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (+/-) 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds. PMID- 27397488 TI - Pain sensitivity in patients with haemophilia following moderate aerobic exercise intervention. AB - BACKGROUND: Physical activity is influenced by pain and vice versa. Although studies recommend exercise therapy for patients with haemophilia (PwH), the influence of physical activity on the pain condition in PwH has not been investigated so far. AIM: Aim of this study was to examine the effect of a treadmill intervention with self-chosen velocity on the acute pain sensitivity in PwH. PATIENTS AND METHODS: Twenty PwH [aged 24-58 years, moderate (n = 3) to severe (n = 17) haemophilia A (n = 17) or B (n = 3)] and 20 control subjects (aged 26-61 years) were included in this study. Eighteen PwH and all controls completed a treadmill intervention for 30 min. Pressure pain thresholds (PPT) in Newton (N) were measured at both the knees, ankles and elbows, sternum and forehead before (pre) and immediately after walking (post). RESULTS: PwH and controls walked with comparable speed (mean speed in km h-1 ; PwH: 3.5, controls: 3.8), resulting in significantly different values of performance-related parameters such as heart rate (mean heart rate per minute; PwH: 102, controls: 86; P <= 0.01). Compared to baseline values, PPT remained unaltered at all landmarks in both groups after walking (e.g. pre/post in Newton; knee right: PwH: 63.1/63.0, controls: 93.8/93.8; left knee: PwH: 62.1/62.7, controls: 90.0/93.4), indicating a non-increasing pain condition. CONCLUSION: Findings of unaltered PPT following moderate aerobic exercise showed initial evidence that PwH are able to perform an endurance exercise with self-chosen velocity for 30 min as recommended, without increasing the acute pain condition. By doing so, PwH can benefit from the positive effects of endurance exercise. PMID- 27397489 TI - In relation to the following article "DLS and zeta potential - What they are and what they are not?" Journal of Controlled Release, 2016, 235, 337-351. AB - This Letter to the Editor is written to provide with a corrigendum along with some short technical notes as additional supplementary materials to the recently published review article in JCR, "DLS and zeta potential - What they are and what they are not?". PMID- 27397490 TI - A review of intranasal formulations for the treatment of seizure emergencies. AB - Epileptic seizure emergencies are life-threatening conditions, which in their most severe form, status epilepticus, have a high mortality rate if not quickly terminated. Treatment requires rapid delivery of anti-epileptics such as benzodiazepines to the brain. The nasal route is attractive due to its non invasiveness, potential for direct nose to brain delivery, high vascularity, relatively large absorptive surface area, and avoidance of intestinal/liver metabolism. However, the limited volume of the nasal cavity and poor water solubility of anti-epileptics restrict absorption, leading to insufficient therapeutic brain levels. This review covers various formulation approaches adopted to improve nasal delivery of drugs, especially benzodiazepines, used to treat seizure emergencies. Other general topics such as nasal anatomy, challenges to nasal delivery, and drug/formulation considerations for nose to brain delivery are also discussed. PMID- 27397491 TI - Enhancing tumor penetration and targeting using size-minimized and zwitterionic nanomedicines. PMID- 27397493 TI - Electrosprayed Montelukast/poly (lactic-co-glycolic acid) particle based coating: A new therapeutic approach towards the prevention of in-stent restenosis. AB - Drug-eluting stents (DESs), have shown promising results in prevention of in stent restenosis after percutaneous coronary intervention (PCI). The elevated level of leukotrienes (LTs) detected in injured arteries after PCI, together with the potential role of LTs in inflammatory cascades and structural alterations in arterial wall provides the rationale for development of therapeutic strategies for prevention of in-stent restenosis using LTs receptor antagonists. Montelukast (MK) is a selective cysLT1 receptor antagonist, with anti-inflammatory and anti proliferative properties, which has been used for treatment of various diseases. Here, we report on the fabrication of MK/PLGA particles by electrospraying, aiming towards the development of particle based coating of DESs. The electrosprayed particles incorporated with 3% and 6% w/w MK exhibited fairly spherical shape with smooth surfaces and narrow size distribution. Sustained release of MK for up to 40days was obtained for both formulations, with higher initial burst release and drug release rate for the particles with higher drug loading. The LTD4 induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) by 35% and 85%, respectively, which was substantially antagonized using MK incorporated particles. Nevertheless, MK antagonism preserved the normal proliferation and migration of human coronary artery endothelial cells (HCAECs). Moreover, MK antagonism inhibited the LTD4 induced phenotypic transition of HCASMCs from contractile to synthetic type. The electrosprayed MK-PLGA particles can be employed as a coating for DESs to inhibit the formation of neointimal hyperplasia responsible for in-stent restenosis, yet preserve the healing rate of the stented vessel. STATEMENT OF SIGNIFICANT: Montelukast (MK) is a selective cysLT1 receptor antagonist, with anti inflammatory and anti-proliferative properties. The LTD4 induced proliferation and migration of human coronary artery smooth muscle cells by 35% and 85%, respectively, which was substantially antagonized using MK incorporated particles. MK antagonism preserved the normal proliferation and migration of human coronary artery endothelial cells. The MK antagonism inhibited the phenotypic transition of human coronary artery smooth muscle cells from contractile to synthetic one induced by LTD4. The electrosprayed MK-PLGA particles can be employed as coating for DESs to inhibit formation of neointimal hyperplasia, responsible for in-stent restenosis. PMID- 27397494 TI - Corrosion-wear of beta-Ti alloy TMZF (Ti-12Mo-6Zr-2Fe) in simulated body fluid. AB - Titanium alloys are popular metallic implant materials for use in total hip replacements. Although, alpha+beta titanium alloys such as Ti-6Al-4V have been the most commonly used alloys, the high Young's modulus (~110GPa) leads to an undesirable stress shielding effect. An alternative is to use beta titanium alloys that exhibit a significantly lower Young's modulus (~70GPa). Femoral stems made of a beta titanium alloy known as TMZF (Ti-12Mo-6Zr-2Fe (wt.%)) have been used as part of modular hip replacements since the early 2000's but these were recalled in 2011 by the US Food & Drug Administration (FDA) due to unacceptable levels of 'wear debris'. The wear was caused by small relative movement of the stem and neck at the junction where they fit together in the modular hip replacement design. In this study, the corrosion and wear properties of the TMZF alloy were investigated in simulated body fluid to identify the reason for the wear debris generation. Ti64 was used as a control for comparison. It is shown that the interaction between the surfaces of Ti64 and TMZF with simulated body fluid is very similar, both from the point of view of the products formed and the kinetics of the reaction. The dry wear behaviour of TMZF is also close to that of Ti64 and consistent with expectations based on Archard's law for abrasive wear. However, wear of Ti64 and TMZF in simulated body fluid show contrasting behaviours. A type of time-dependent wear test is used to examine the synergy between corrosion and wear of TMZF and Ti64. It is shown that the wear of TMZF accelerated rapidly in SBF whereas that of Ti64 is reduced. The critical role of the strain hardening capacity of the two materials and its role in helping the surface resist abrasion by hydroxyapatite particles formed as a result of the reaction with the SBF is discussed and recommendations are made for modifications that could be made to the TMZF alloy to improve the corrosion-wear response. STATEMENT OF SIGNIFICANCE: TMZF is a low modulus beta-Ti alloy that has been used as the femoral stem in the Stryker modular design total hip replacement. It went into service in the early 2000's but was recalled by the FDA in 2011 due to unacceptable levels of wear debris released in the body which led to adverse physiological reactions. A large number of these implants remain in patients today. In this contribution, we investigate the corrosion (interaction of the alloy with simulated body fluid (SBF)), dry wear and then corrosion-wear in SBF to identify the origin of the unacceptable levels of wear that led to the FDA recall of this material. We use Ti-6Al-4V as a control and demonstrate that the reaction between Ti64 and TMZF with SBF is very similar in terms of both products formed and kinetics. We also show that the dry wear behaviour of TMZF is very similar to that of Ti64 and exactly as should be expected for the hardness of this material. However, the wear behaviours of TMZF and Ti64 are completed different in SBF and wear of TMZF is significantly accelerated in SBF. A type of time-dependent wear test is used to demonstrate the synergy between corrosion and wear and the key role of the strain hardening capacity (or lack thereof in the case of beta-Ti) is discussed. PMID- 27397495 TI - Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents. AB - A series of N(9)-substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N(9)-substituted harmine derivatives had anticancer effects. In particular, N(9)-haloalkyl derivatives 9a-9c and N(9)-acyl harmine derivatives 11c and 11d, with IC50 values less than 1MUM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure-activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N(9)-position of harmine could significantly increase the anticancer activity. The most active compound (11d) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner. PMID- 27397492 TI - Self Managing Heart Failure in Remote Australia - Translating Concepts into Clinical Practice. AB - Congestive heart failure (CHF) is an ambulatory health care condition characterized by episodes of decompensation and is usually without cure. It is a leading cause for morbidity and mortality and the lead cause for hospital admissions in older patients in the developed world. The long-term requirement for medical care and pharmaceuticals contributes to significant health care costs. CHF management follows a hierarchy from physician prescription to allied health, predominately nurse-led, delivery of care. Health services are easier to access in urban compared to rural settings. The differentials for more specialized services could be even greater. Remote Australia is thus faced with unique challenges in delivering CHF best practice. Chronic disease self management programs (CDSMP) were designed to increase patient participation in their health and alleviate stress on health systems. There have been CDSMP successes with some diseases, although challenges still exist for CHF. These challenges are amplified in remote Australia due to geographic and demographic factors, increased burden of disease, and higher incidence of comorbidities. In this review we explore CDSMP for CHF and the challenges for our region. PMID- 27397496 TI - Antidiabetic effect, antioxidant activity, and toxicity of 3',4'-Di-O-acetyl-cis khellactone in Streptozotocin-induced diabetic rats. AB - Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3',4'-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15mg/kg (p<0.05) compared with the diabetic control group, and demonstrated a statistically significant increase in weight gain (45.7+/-9.7 in the group treated with DOAcK vs. -23.0+/-33.1 in the group with diabetes). In a biochemical profile, DOAcK did not modify lipid metabolism and did not cause damage at the renal level. DOAcK administration increased the activities of Catalase (CAT), Glutathione Peroxidase (GPx), and Super Oxide Dismutase (SOD) to levels near those of the healthy group. Histopathological analysis exhibited morphology similar to that of the healthy group and the group treated with DOAcK. DOAcK is not mutagenic by Ames test for Salmonella typhimurium strains TA98, TA100, or TA102, and is not genotoxic by Micronucleus assay; median lethal dose (LD50) >2000mg/kg and, at this dose, no signs of toxicity or death were reported after 14days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested. PMID- 27397497 TI - Preparation, biological evaluation and molecular docking study of imidazolyl dihydropyrimidines as potential Mycobacterium tuberculosis dihydrofolate reductase inhibitors. AB - A series of novel dihydropyrimidine derivatives bearing an imidazole nucleus at C 4 position were synthesized in excellent yields via Biginelli multi-component reaction. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR and Mass spectroscopy. In vitro antitubercular evaluation of all the newly synthesized compounds 4a-p against Mycobacterium tuberculosis (Mtb) H37Rv showed, 4j (MIC: 0.39MUg/mL; SI: >25.64), 4m (MIC: 0.78MUg/mL; SI: >12.82) and 4p (MIC: 0.39MUg/mL; SI: 24.10) as the most promising lead analogues. Compounds 4j, 4m and 4p displayed effective reduction in residual Mtb growth within the tuberculosis-infected macrophage model. Further, molecular docking study of active molecules 4j, 4m and 4p against Mycobacterium tuberculosis dihydrofolate reductase (Mtb DHFR) proved their potency as Mtb DHFR inhibitors acting as potential leads for further development. Pharmacokinetic properties leading to drug-likeness were also predicted for most active molecules 4j, 4m and 4p. PMID- 27397498 TI - Design and synthesis of 4'-O-alkylamino-tethered-benzylideneindolin-2-ones as potent cytotoxic and apoptosis inducing agents. AB - A series of new 4'-O-alkylamino-tethered-benzylideneindolin-2-one derivatives has been synthesized and evaluated for their anti-proliferative activity against selected human cancer cell lines of lung (A549), prostate (DU-145), breast (BT549 and MDA-MB-231) and normal breast epithelial cells (MCF-10A). Gratifyingly, the compounds 5j, 5o and 5r exhibited potent cytotoxicity against breast cancer cell lines (BT549 and MDA-MB-231) with IC50 values in the range of 1.26-2.77MUM, and are found to be safer with lesser cytotoxicity on normal breast epithelial cells (MCF-10A). Further, experiments were conducted with these compounds 5j, 5o and 5r on MDA-MB-231 cancer cells to study the mechanism of growth inhibition and apoptosis inducing effect. Treatment of MDA-MB-231 cells with test compounds resulted in inhibition of cell migration through disorganization and disruption of F-actin capping protein. The flow-cytometry analysis results showed that the compound 5o arrested MDA-MB-231 cells in G0/G1 phase of cell cycle in a dose dependent manner. Hoechst staining study revealed that the test compounds inhibited tumor cell proliferation through induction of apoptosis. In addition, the mitochondrial membrane potential (DPsim) was affected and the increased level of reactive oxygen species (ROS) was noted in MDA-MB-231 cells. PMID- 27397499 TI - Discovery of novel dihydrobenzofuran cyclopropane carboxylic acid based calcium sensing receptor antagonists for the treatment of osteoporosis. AB - In a search for novel small molecule calcium-sensing receptor (CaSR) antagonists as oral bone anabolic agents, we discovered dihydrobenzofuran cyclopropane carboxylic acid derivatives, such as 12f (IC50=27.6nM), are highly potent calcium sensing receptor antagonists. Studies in rats established that compound 12f stimulates parathyroid hormone (PTH) release in a fast-acting, pulsatile manner. PMID- 27397500 TI - Development of a cell viability assay to assess drug metabolite structure toxicity relationships. AB - Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites. In order to reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, we developed a simple cell viability assay by combining a bioactivation system (human CYP3A4, CYP2D6 and CYP2C9) with Hep3B cells. We screened a series of drugs to explore structural motifs that may be responsible for CYP450-dependent activation caused by reactive metabolite formation, which highlighted specific liabilities regarding certain phenols and anilines. PMID- 27397501 TI - Comparison of reliability and repeatability of corneal curvature assessment with six keratometers. AB - BACKGROUND: Keratometric methodology varies between instruments and the differences may have a clinical impact. We investigated the agreement and reproducibility of six keratometers. METHODS: Keratometry was performed on 100 subjects at two separate sessions with IOLMaster 500, Pentacam, OPD scanner, Medmont E300, Javal-Schiotz and TMS-5. A second observer assessed 30 subjects to determine inter-observer variability. A single individual was assessed on 10 separate sessions to determine intra-observer variability. Data were analysed using coefficient of variation (CV) and intra-class correlation coefficient (ICCC) for intra-observer variation. Inter-observer concordance was evaluated by the ICCC. Bland-Altman plots, Pearson's correlation coefficient and repeated measures analysis of variance were used to assess agreement of data produced by the instruments. RESULTS: OPD scanner and Javal-Schiotz mean spherical equivalent (MSE) results were systematically different (p < 0.001) from other instruments (flatter and steeper, respectively). J0 /J45 were similar for all instruments (p < 0.05). Bland-Altman comparison plots indicated that Pentacam and IOLMaster demonstrated greatest level of agreement (ICC results MSE = 0.992, J0 = 0.934 and J45 = 0.890). Agreement (ICC) between observers for MSE ranged from 0.955 to 0.995 for all instruments; lower levels of agreement were found for J0 /J45 (0.289 to 0.901). IOLMaster showed greatest correlation and Medmont the lowest. All instruments showed high intra-observer repeatability of MSE (CV 0.1 to 0.3 per cent). The J0 /J45 readings showed greater variability (CV range 8.8 to 57.6 per cent). CONCLUSION: When considering MSE alone IOLMaster, Pentacam, OPD scan and Medmont may be considered interchangeable; however, assessment of astigmatism shows greater variability between instruments, sessions and observers. PMID- 27397502 TI - Structural analysis of Pseudomonas aeruginosa H3-T6SS immunity proteins. AB - The Pseudomonas aeruginosa PldB protein is a transkingdom effector secreted by the Type VI Secretion System (T6SS). PA5088, PA5087, and PA5086 are three immunity proteins that can suppress the virulence of PldB. We report the crystal structures of PA5088 and PA5087 at 2.0 and 2.1 A resolution, respectively. PA5088 and PA5087 both consist of several Sel1-like Repeats (SLRs) and form super-ring folds. Our structural analysis of these proteins revealed key differences among PA5088, PA5087, and their homologs. Our docking experiments have shed light on the putative interaction mechanism of their function as phospholipase D inhibitors. PMID- 27397503 TI - Silent Tyrosinemia Type I Without Elevated Tyrosine or Succinylacetone Associated with Liver Cirrhosis and Hepatocellular Carcinoma. AB - Tyrosinemia type I (TYRSN1, TYR I) is caused by fumarylacetoacetate hydrolase (FAH) deficiency and affects approximately one in 100,000 individuals worldwide. Pathogenic variants in FAH cause TYRSN1, which induces cirrhosis and can progress to hepatocellular carcinoma (HCC). TYRSN1 is characterized by the production of a pathognomonic metabolite, succinylacetone (SUAC) and is included in the Recommended Uniform Screening Panel for newborns. Treatment intervention is effective if initiated within the first month of life. Here, we describe a family with three affected children who developed HCC secondary to idiopathic hepatosplenomegaly and cirrhosis during infancy. Whole exome sequencing revealed a novel homozygous missense variant in FAH (Chr15(GRCh38):g.80162305A>G; NM_000137.2:c.424A > G; NP_000128.1:p.R142G). This novel variant involves the catalytic pocket of the enzyme, but does not result in increased SUAC or tyrosine, making the diagnosis of TYRSN1 problematic. Testing this novel variant using a rapid, in vivo somatic mouse model showed that this variant could not rescue FAH deficiency. In this case of atypical TYRSN1, we show how reliance on SUAC as a primary diagnostic test can be misleading in some patients with this disease. Augmentation of current screening for TYRSN1 with targeted sequencing of FAH is warranted in cases suggestive of the disorder. PMID- 27397505 TI - A Landscape of Pharmacogenomic Interactions in Cancer. AB - Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of alterations that sensitize to drugs, while machine learning demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations. PMID- 27397504 TI - Food-based natural products for cancer management: Is the whole greater than the sum of the parts? AB - The rise in cancer incidence and mortality in developing countries together with the human and financial cost of current cancer therapy mandates a closer look at alternative ways to overcome this burgeoning global healthcare problem. Epidemiological evidence for the association between cancer and diet and the long latency of most cancer progression have led to active exploration of whole and isolated natural chemicals from different naturally occurring substances in various preclinical and clinical settings. In general the lack of systemic toxicities of most 'whole' and 'isolated' natural compounds, their potential to reduce toxic doses and potential to delay the development of drug-resistance makes them promising candidates for cancer management. This review article examines the suggested molecular mechanisms affected by these substances focusing to a large extent on prostate cancer and deliberates on the disparate results obtained from cell culture, preclinical and clinical studies in an effort to highlight the use of whole extracts and isolated constituents for intervention. As such these studies underscore the importance of factors such as treatment duration, bioavailability, route of administration, selection criteria, standardized formulation and clinical end points in clinical trial design with both entities. Overall lack of parallel comparison studies between the whole natural products and their isolated compounds limits decisive conclusions regarding the superior utility of one over the other. We suggest the critical need for rigorous comparative research to identify which one of the two or both entities from nature would be best qualified to take on the mantle of cancer management. PMID- 27397506 TI - Ultra-High Resolution 3D Imaging of Whole Cells. AB - Fluorescence nanoscopy, or super-resolution microscopy, has become an important tool in cell biological research. However, because of its usually inferior resolution in the depth direction (50-80 nm) and rapidly deteriorating resolution in thick samples, its practical biological application has been effectively limited to two dimensions and thin samples. Here, we present the development of whole-cell 4Pi single-molecule switching nanoscopy (W-4PiSMSN), an optical nanoscope that allows imaging of three-dimensional (3D) structures at 10- to 20 nm resolution throughout entire mammalian cells. We demonstrate the wide applicability of W-4PiSMSN across diverse research fields by imaging complex molecular architectures ranging from bacteriophages to nuclear pores, cilia, and synaptonemal complexes in large 3D cellular volumes. PMID- 27397508 TI - Childhood psychopathology in children of women with eating disorders. AB - OBJECTIVE: We aimed to investigate the effect of maternal eating disorders (ED) on childhood psychopathology, early delays in cognitive, motor and language development, mother and child relationship, and child temperament in a community based cohort: the Danish National Birth Cohort (DNBC). METHOD: Data were obtained prospectively on 48 403 children at 18 months and 46 156 children at 7 years. Data on cognitive, motor and language development, temperament and attachment were obtained at 18 months; data on child psychopathology were obtained at 7 years of age, using the Strengths and Difficulties Questionnaire (SDQ). Children of mothers with lifetime diagnosis of anorexia nervosa (AN, n = 931), lifetime diagnosis of bulimia nervosa (BN, n = 906) and both (AN & BN = 360) were compared to children of mothers without an ED (n = 46 206). RESULTS: Girls of women with lifetime AN had higher odds of having emotional problems, and girls of women with lifetime BN of having conduct problems compared with children of healthy women. Boys of women with lifetime AN had higher odds of total, emotional and conduct problems; boys of women with lifetime BN had higher odds of total, conduct, hyperactivity and peer difficulties compared to children of women without an ED. Boys of women with lifetime AN and BN had higher odds of total, emotional and peer problems compared to children of healthy women. CONCLUSION: Maternal ED is associated with childhood psychopathology in both boys and girls. Boys seemed at higher risk for psychopathology in this sample. Associations between emotional disorders across genders in children of mothers with lifetime AN, and hyperactivity and peer difficulties in boys of mothers with lifetime BN confirm and extend previous findings and point to possible shared risk between ED and other psychopathology. PMID- 27397507 TI - Pre-assembled Nuclear Pores Insert into the Nuclear Envelope during Early Development. AB - Nuclear pore complexes (NPCs) span the nuclear envelope (NE) and mediate nucleocytoplasmic transport. In metazoan oocytes and early embryos, NPCs reside not only within the NE, but also at some endoplasmic reticulum (ER) membrane sheets, termed annulate lamellae (AL). Although a role for AL as NPC storage pools has been discussed, it remains controversial whether and how they contribute to the NPC density at the NE. Here, we show that AL insert into the NE as the ER feeds rapid nuclear expansion in Drosophila blastoderm embryos. We demonstrate that NPCs within AL resemble pore scaffolds that mature only upon insertion into the NE. We delineate a topological model in which NE openings are critical for AL uptake that nevertheless occurs without compromising the permeability barrier of the NE. We finally show that this unanticipated mode of pore insertion is developmentally regulated and operates prior to gastrulation. PMID- 27397509 TI - Diffusion and precipitation processes in iron-based silica gardens. AB - Silica gardens are tubular structures that form along the interface of multivalent metal salts and alkaline solutions of sodium silicate, driven by a complex interplay of osmotic and buoyant forces together with chemical reaction. They display peculiar plant-like morphologies and thus can be considered as one of the few examples for the spontaneous biomimetic self-ordering of purely inorganic materials. Recently, we could show that silica gardens moreover are highly dynamic systems that remain far from equilibrium for considerable periods of time long after macroscopic growth is completed. Due to initial compartmentalisation, drastic concentration gradients were found to exist across the tube walls, which give rise to noticeable electrochemical potential differences and decay only slowly in a series of coupled diffusion and precipitation processes. In the present work, we extend these studies and investigate the effect of the nature of the used metal cations on the dynamic behaviour of the system. To that end, we have grown single macroscopic silica garden tubes by controlled addition of sodium silicate sol to pellets of iron(ii) and iron(iii) chloride. In the following, the concentrations of ionic species were measured as a function of time on both sides of the formed membranes, while electrochemical potentials and pH were monitored online by immersing the corresponding sensors into the two separated solution reservoirs. At the end of the experiments, the solid tube material was furthermore characterised with respect to composition and microstructure by a combination of ex situ techniques. The collected data are compared to the previously reported case of cobalt-based silica gardens and used to shed light on ion diffusion through the inorganic membranes as well as progressive mineralisation at both surfaces of the tube walls. Our results reveal important differences in the dynamics of the three studied systems, which can be explained based on the acidity of the metal cations and the porosity of the membranes, leading to substantially dissimilar time dependent solution chemistry as well as distinct final mineral structures. The insight gained in this work may help to better understand the diffusion properties and precipitation patterns in tubular iron (hydr)oxide/silicate structures observed in geological environments and during steel corrosion. PMID- 27397510 TI - Educational status and differences in left ventricular mass and ejection fraction - The role of BMI and parameters related to the metabolic syndrome: A longitudinal analysis from the population-based CARLA cohort. AB - BACKGROUND AND AIMS: Higher ventricular mass has been reported in non-white US Americans with low educational status and in socially isolated people. To assess the impact of education on cardiac mass and function in the general population and to identify mediators. METHODS AND RESULTS: Data from a German population based sample were used (CARLA cohort, n = 1779 at baseline, n = 1436 at the four year follow-up). Ventricular mass indexed on height (LVMI) and ejection fraction, using Teichholz's formula (EFTZ), were measured. Education was assessed using the ISCED classification. Mediator analyses were performed using the R-macro 'mediation' to compute the average direct effect and the average causal mediated effect after confounder adjustment. Sensitivity analyses for unobserved confounders were performed. Considered mediators were BMI, waist-to-hip ratio, HbA1c, and systolic and diastolic blood pressures. We found differences in LVMI and EFTZ, both at baseline and follow-up, between educational levels in women (lowest vs highest educational level: 15.6 g, 95% CI: -25.7, -5.6), but not in men. Similarly, women (lowest vs highest educational level at baseline: 3.3%, 95% CI: 0.8-5.7), but not men, of higher educational levels had a higher EFTZ of comparable magnitude at baseline and follow-up. Of the considered mediators, BMI explained 55.9% at baseline and 54.1% at follow-up of the educational effect, while other potential mediators had no significant effect. Relations remained constant between baseline and follow-up. CONCLUSIONS: Women with low educational levels tend to have a higher ventricular mass and lower EF, which can be explained by a higher BMI in this group. PMID- 27397511 TI - Dietary quality indices in relation to cardiometabolic risk among Finnish children aged 6-8 years - The PANIC study. AB - BACKGROUND AND AIMS: There are no studies on the relationships of dietary quality indices to the clustering of cardiometabolic risk factors in children. We therefore investigated the associations of four dietary quality indices with cardiometabolic risk score and cardiometabolic risk factors in Finnish children. METHODS AND RESULTS: Subjects were a population sample of 204 boys and 198 girls aged 6-8 years. We assessed diet by 4-day food records and calculated Dietary Approaches to Stop Hypertension (DASH) Score, Baltic Sea Diet Score (BSDS), Mediterranean Diet Score (MDS), and Finnish Children Healthy Eating Index (FCHEI). We calculated the age- and sex-adjusted cardiometabolic risk score summing up Z-scores for waist circumference, mean of systolic and diastolic blood pressure and concentrations of fasting serum insulin and fasting plasma glucose, triglycerides and HDL cholesterol, the last multiplying by -1. Higher FCHEI was associated with lower cardiometabolic risk score among boys (standardised regression coefficient beta = -0.14, P = 0.044) adjusted for age, physical activity, electronic media time and household income. Higher DASH Score was related to a lower serum insulin in boys (beta = -0.15, P = 0.028). Higher DASH Score (beta = -0.16, P = 0.023) and FCHEI (beta = -0.17, P = 0.014) were related to lower triglyceride concentration in boys. Higher FCHEI was associated with lower triglyceride concentration in girls (beta = -0.16, P = 0.033). Higher DASH Score (beta = -0.19, P = 0.011) and BSDS (beta = -0.23, P = 0.001) were associated with lower plasma HDL cholesterol concentration in girls. CONCLUSION: Higher FCHEI was associated with lower cardiometabolic risk among boys, whereas DASH Score, BSDS or MDS were not associated with cardiometabolic risk in children. PMID- 27397512 TI - Realizing the Potential for Recipient Immune Cells in Adoptive Immune Therapy. PMID- 27397513 TI - Neurons Derived From Patient-Specific Induced Pluripotent Stem Cells: a Promising Strategy Towards Developing Novel Pharmacotherapies for Autism Spectrum Disorders. PMID- 27397515 TI - Spinodally Decomposed PbSe-PbTe Nanoparticles for High-Performance Thermoelectrics: Enhanced Phonon Scattering and Unusual Transport Behavior. AB - Dramatic enhancements in the figure of merit have been obtained in bulk thermoelectric materials by doping, band engineering, and nanostructuring. Especially, in p-type thermoelectrics, high figure of merits near 2.0 have been reported in a few papers through the reduction in lattice thermal conductivity and the advancement in power factors. However, there exists no report on the n type systems showing high figure of merits because of their intrinsically low Seebeck coefficients. Here, we demonstrate that a nanostructured bulk n-type thermoelectric material that was assembled by sintering spinodally decomposed lead chalcogenide nanoparticles having a composition of PbSe0.5Te0.5 reaches a high figure of merit of 1.85. The spinodally decomposed nanoparticles permit our thermoelectric material to have extremely low lattice thermal conductivity and a high power factor as a result of nanostructuring, electronic optimization, insertion of an impurity phase and phase change in local areas. We propose that this interesting concept would be one of the promising approaches that overcome limitation arising from the fact that most parameters in the figure of merit are closely correlated. PMID- 27397514 TI - The Dynamic Role of the IL-33/ST2 Axis in Chronic Viral-infections: Alarming and Adjuvanting the Immune Response. AB - Interleukin 33 (IL-33), a member of the IL-1 family, is constitutively expressed in epithelial and in endothelial cells at barrier sites, acting as a danger signal and adjuvanting the immune response following tissue damage and infection. Originally implicated in allergy, IL-33 is also known to be involved in innate and adaptive immune responses by enhancing natural killer, Th1, and CD4 and CD8 T cell functions. The nature of the antiviral immune response orchestrated by IL-33 depends on the site of infection, the duration of the disease and the cytokine milieu. In this review, we focus on the distinctive contribution of IL-33 as an anti-infective and proinflammatory cytokine in response to cell death and viral infections. The dynamic role of IL-33 in the acute and chronic phases of infection with HIV, hepatitis B and C viruses, and with CMV is highlighted. This review will also discuss the potential immunotherapeutic and adjuvant roles of IL 33. SEARCH STRATEGY AND SELECTION CRITERIA: English language, indexed publications in PubMed were searched using combinations of following key words: "interleukin-33", "IL-33", "suppression of tumorigenicity 2", ST2", "sST2", "HIV", "HBV", "HCV", "CMV", "HPV", "immunotherapy" and "vaccine". Except for seminal studies, only articles published between 2010 and 2016 were included. PMID- 27397516 TI - Structural Basis for Plexin Activation and Regulation. AB - Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development and plasticity, ranging from axon guidance and neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization, but extracellular regulation and activation mechanisms remain unclear. Here we present crystal structures of PlxnA (PlxnA1, PlxnA2, and PlxnA4) full ectodomains. Domains 1-9 form a ring-like conformation from which the C-terminal domain 10 points away. All our PlxnA ectodomain structures show autoinhibitory, intermolecular "head-to-stalk" (domain 1 to domain 4-5) interactions, which are confirmed by biophysical assays, live cell fluorescence microscopy, and cell-based and neuronal growth cone collapse assays. This work reveals a 2-fold role of the PlxnA ectodomains: imposing a pre-signaling autoinhibitory separation for the cytoplasmic domains via intermolecular head-to stalk interactions and supporting dimerization-based PlxnA activation upon ligand binding. More generally, our data identify a novel molecular mechanism for preventing premature activation of axon guidance receptors. PMID- 27397517 TI - Sublayer-Specific Coding Dynamics during Spatial Navigation and Learning in Hippocampal Area CA1. AB - The mammalian hippocampus is critical for spatial information processing and episodic memory. Its primary output cells, CA1 pyramidal cells (CA1 PCs), vary in genetics, morphology, connectivity, and electrophysiological properties. It is therefore possible that distinct CA1 PC subpopulations encode different features of the environment and differentially contribute to learning. To test this hypothesis, we optically monitored activity in deep and superficial CA1 PCs segregated along the radial axis of the mouse hippocampus and assessed the relationship between sublayer dynamics and learning. Superficial place maps were more stable than deep during head-fixed exploration. Deep maps, however, were preferentially stabilized during goal-oriented learning, and representation of the reward zone by deep cells predicted task performance. These findings demonstrate that superficial CA1 PCs provide a more stable map of an environment, while their counterparts in the deep sublayer provide a more flexible representation that is shaped by learning about salient features in the environment. VIDEO ABSTRACT. PMID- 27397518 TI - A Distributed Recurrent Network Contributes to Temporally Precise Vocalizations. AB - How do forebrain and brainstem circuits interact to produce temporally precise and reproducible behaviors? Birdsong is an elaborate, temporally precise, and stereotyped vocal behavior controlled by a network of forebrain and brainstem nuclei. An influential idea is that song premotor neurons in a forebrain nucleus (HVC) form a synaptic chain that dictates song timing in a top-down manner. Here we combine physiological, dynamical, and computational methods to show that song timing is not generated solely by a mechanism localized to HVC but instead is the product of a distributed and recurrent synaptic network spanning the forebrain and brainstem, of which HVC is a component. PMID- 27397521 TI - Utility of Pediatric Nerve Biopsy in Tertiary Care Referral. AB - Investigators from Mayo Clinic in Rochester, MN, report the utility of nerve biopsy as a diagnostic tool in their institution. PMID- 27397519 TI - Neuromodulatory Regulation of Behavioral Individuality in Zebrafish. AB - Inter-individual behavioral variation is thought to increase fitness and aid adaptation to environmental change, but the underlying mechanisms are poorly understood. We find that variation between individuals in neuromodulatory input contributes to individuality in short-term habituation of the zebrafish (Danio Rerio) acoustic startle response (ASR). ASR habituation varies greatly between individuals, but differences are stable over days and are heritable. Acoustic stimuli that activate ASR-command Mauthner cells also activate dorsal raphe nucleus (DRN) serotonergic neurons, which project to the vicinity of the Mauthner cells and their inputs. DRN neuron activity decreases during habituation in proportion to habituation and a genetic manipulation that reduces serotonin content in DRN neurons increases habituation, whereas serotonergic agonism or DRN activation with ChR2 reduces habituation. Finally, level of rundown of DRN activity co-segregates with extent of behavioral habituation across generations. Thus, variation between individuals in neuromodulatory input contributes to individuality in a core adaptive behavior. VIDEO ABSTRACT. PMID- 27397520 TI - Real-Time Imaging Reveals Properties of Glutamate-Induced Arc/Arg 3.1 Translation in Neuronal Dendrites. AB - The immediate early gene Arc (also Arg3.1) produces rapid changes in synaptic properties that are linked to de novo translation. Here we develop a novel translation reporter that exploits the rapid maturation and "flash" kinetics of Gaussia luciferase (Gluc) to visualize Arc translation. Following glutamate stimulation, discrete Arc-Gluc bioluminescent flashes representing sites of de novo translation are detected within 15 s at distributed sites in dendrites, but not spines. Flashes are episodic, lasting ~20 s, and may be unitary or repeated at ~minute intervals at the same sites. Analysis of flash amplitudes suggests they represent the quantal product of one or more polyribosomes, while inter flash intervals appear random, suggesting they arise from a stochastic process. Surprisingly, glutamate-induced translation is dependent on Arc open reading frame. Combined observations support a model in which stalled ribosomes are reactivated to rapidly generate Arc protein. PMID- 27397522 TI - Comparison of pregabalin with doxepin in the management of uremic pruritus: a randomized single blind clinical trial. AB - INTRODUCTION: Pruritus is one of the frustrating skin manifestations of advanced renal failure. Many options have been used for the management of uremic pruritus (UP) such as pregabalin. There are some studies that reported beneficial effects of pregabalin in reducing UP; however, most of them did not have a comparator arm. Therefore, we designed this study to compare antipruritic effects of pregabalin with doxepin in the management of pruritus in hemodialysis patients. METHODS: Seventy-two patients suffering from UP were randomly assigned to receive pregabalin (50 mg every other day) or doxepin (10 mg per day) for 4 weeks. Severity of pruritus and its effect on quality of life were assessed by visual analog scale (VAS), 5-D itch scale and dermatology life quality index (DLQI) at baseline and after 1 week, 2 weeks and 4 weeks of the treatment. FINDINGS: Mean scores of the VAS decreased from 7.5+/- 1.4 and 7.1 +/- 1.3 at baseline to 2.1 +/ 2.6 and 4.2 +/- 2.6 at the end of the study (P < 0.001) in the pregabalin and doxepin groups, respectively. Similarly, pregabalin significantly reduced mean scores of the 5-D itch scale and the DLQI compared to doxepin. The most reported side effect in each group was somnolence which occurred in similar rates in the both groups. DISCUSSION: Pregabalin was more effective than doxepin in reducing the severity of uremic pruritus and improving the quality of life of patients in this study, so we suggest that clinician can consider pregabalin prior to using antihistamine drugs in the management of severe itch in hemodialysis patients. PMID- 27397523 TI - Phytoplankton phenotype plasticity induced by phosphorus starvation may play a significant role in marine microbial ecology and biogeochemistry. PMID- 27397525 TI - Corrigendum. PMID- 27397524 TI - Do stomata of evolutionary distant species differ in sensitivity to environmental signals? PMID- 27397526 TI - Response to Risk of Avalanche Involvement in Winter Backcountry Recreation: The Advantage of Small Groups by Zweifel et al. PMID- 27397527 TI - In Response to Xylocopa tranquebarica Fatal Stinging by Kularatne et al. PMID- 27397529 TI - Editor's Notes. PMID- 27397528 TI - Myopic Changes in a Climber after Taking Acetazolamide and the Use of Corrective Lenses to Temporize Symptoms: A Case Report from Mount Kilimanjaro. AB - When performing detailed tasks related to climbing or hiking, accurate vision is important for safety. Acetazolamide is a medication commonly used to prevent acute mountain sickness, but it has an uncommon side effect of transient myopia. Reports of this side effect are mainly associated with its use in obstetrics, where it is often prescribed in higher doses than used in acute mountain sickness prophylaxis. We describe the case of a climber taking low-dose acetazolamide who developed transient myopia. We further describe potential mechanisms of this rare side effect as well as a novel approach of field management utilizing possible materials at hand. PMID- 27397530 TI - The Medical Bookshelf. PMID- 27397531 TI - Problems+Solutions. PMID- 27397534 TI - Infectious disease. PMID- 27397532 TI - Washington Medical Update. PMID- 27397535 TI - Anaerobic pleuropulmonary infections. PMID- 27397537 TI - Primary Care Digest. PMID- 27397539 TI - Semi-varying coefficient multinomial logistic regression for disease progression risk prediction. AB - This paper proposes a risk prediction model using semi-varying coefficient multinomial logistic regression. We use a penalized local likelihood method to do the model selection and estimate both functional and constant coefficients in the selected model. The model can be used to improve predictive modelling when non linear interactions between predictors are present. We conduct a simulation study to assess our method's performance, and the results show that the model selection procedure works well with small average numbers of wrong-selection or missing selection. We illustrate the use of our method by applying it to classify the patients with early rheumatoid arthritis at baseline into different risk groups in future disease progression. We use a leave-one-out cross-validation method to assess its correct prediction rate and propose a recalibration framework to evaluate how reliable are the predicted risks. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27397540 TI - Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer. AB - AIM: Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2 targeted compounds have been reported. In this study, we identified a novel Pim-2 inhibitor, HJ-PI01, by in silico analysis and experimental validation. METHODS: The protein-protein interaction (PPI) network, chemical synthesis, molecular docking, and molecular dynamics (MD) simulations were used to design and discover the new Pim-2 inhibitor HJ-PI01. The anti-tumor effects of HJ-PI01 were evaluated in human breast MDA-MB-231, MDA-MB-468, MDA-MB-436, MCF-7 cells in vitro and in MDA-MB-231 xenograft mice, which were treated with HJ-PI01 (40 mg.kg(-1).d(-1), ig) with or without lienal polypeptide (50 mg.kg(-1).d(-1), ip) for 10 d. The apoptosis/autophage-inducing mechanisms of HJ-PI01 were elucidated using Western blots, immunoblots, flow cytometry, transmission electron microscopy and fluorescence microscopy. RESULTS: Based on the PrePPI network, the potential partners interacting with Pim-2 in regulating apoptosis (160 protein pairs) and autophagy (47 protein pairs) were identified. Based on the structural characteristics of Pim-2, a total of 15 compounds (HJ-PI01 to HJ-P015) were synthesized, which showed moderate or remarkable anti-proliferative potency in the human breast cancer cell lines tested. The most effective compound HJ-PI01 exerted a robust inhibition on MDA-MB-231 cells compared with chlorpromazine and the pan-Pim inhibitor PI003. Molecular dynamics (MD) simulation revealed that HJ PI01 had a good binding score with Pim-2. Moreover, HJ-PI01 (300 nmol/L) induced death receptor-dependent and mitochondrial apoptosis as well as autophagic death in MDA-MB-231 cells. In MDA-MB-231 xenograft mice, administration of HJ-PI01 remarkably inhibited the tumor growth and induced tumor cell apoptosis in vivo. Co-administration of HJ-PI01 with lienal polypeptide could improve the anti-tumor activity of HJ-PI01 and reduce its toxicity. CONCLUSION: The newly synthesized compound, HJ-PI01, can induce death receptor/mitochondrial apoptosis and autophagic cell death by targeting Pim-2 in human breast cancer cells in vitro and in vivo. PMID- 27397541 TI - Histone lysine methyltransferases as anti-cancer targets for drug discovery. AB - Post-translational epigenetic modification of histones is controlled by a number of histone-modifying enzymes. Such modification regulates the accessibility of DNA and the subsequent expression or silencing of a gene. Human histone methyltransferases (HMTs)constitute a large family that includes histone lysine methyltransferases (HKMTs) and histone/protein arginine methyltransferases (PRMTs). There is increasing evidence showing a correlation between HKMTs and cancer pathogenesis. Here, we present an overview of representative HKMTs, including their biological and biochemical properties as well as the profiles of small molecule inhibitors for a comprehensive understanding of HKMTs in drug discovery. PMID- 27397542 TI - Translocation of PKG1alpha acts on TRPV4-C1 heteromeric channels to inhibit endothelial Ca(2+) entry. AB - AIM: TRPV4-C1 heteromeric channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. However, the negative regulation of these channels is not fully understood. This study was conducted to investigate the inhibitory effect of PKG1alpha on TRPV4-C1 heteromeric channels. METHODS: Immuno fluorescence resonance energy transfer (FRET) was used to explore the spatial proximity of PKG1alpha and TRPC1. Phosphorylation of endogenous TRPC1 was tested by phosphorylation assay. [Ca(2+)]i transients and cation current in MAECs were assessed with Fura-2 fluorescence and whole-cell recording, respectively. In addition, rat mesenteric arteries segments were prepared, and vascular relaxation was examined with wire myography. RESULTS: In immuno-FRET experiments, after exposure of these cells to 8-Br-cGMP, more PKG1alpha was observed in the plasma membrane, and PKG1alpha and TRPC1 were observed to be in closer proximity. TAT TRPC1(S172) and TAT-TRPC1(T313) peptide fragments, which contain the PKG targeted residues Ser172 and Thr313, respectively, were introduced into isolated endothelial cells to abrogate the translocation of PKG1alpha. Furthermore, a phosphorylation assay demonstrated that PKG directly phosphorylates TRPC1 at Ser172 and Thr313 in endothelial cells. In addition, PKG activator 8-Br-cGMP markedly reduced the magnitude of the 4alphaPDD-induced and 11,12-EET-induced [Ca(2+)]i transients, the cation current and vascular relaxation. CONCLUSION: This study uncovers a novel mechanism by which PKG negatively regulates endothelial heteromeric TRPV4-C1 channels through increasing the spatial proximity of TRPV4-C1 to PKG1alpha via translocation and through phosphorylating Ser172 and Thr313 of TRPC1. PMID- 27397543 TI - Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest. AB - AIM: Recent studies have shown that the two-pore-domain potassium channel TREK-1 is involved in the proliferation of neural stem cells, astrocytes and human osteoblasts. In this study, we investigated how TREK-1 affected the proliferation of Chinese hamster ovary (CHO) cells in vitro. METHODS: A CHO cell line stably expressing hTREK-1 (CHO/hTREK-1 cells) was generated. TREK-1 channel currents in the cells were recorded using whole-cell voltage-clamp recording. The cell cycle distribution was assessed using flow cytometry analysis. The expression of major signaling proteins involved was detected with Western blotting. RESULTS: CHO/hTREK-1 cells had a high level of TREK-1 expression, reached up to 320%+/-16% compared to the control cells. Application of arachidonic acid (10 MUmol/L), chloroform (1 mmol/L) or etomidate (10 MUmol/L) substantially increased TREK-1 channel currents in CHO/hTREK-1 cells. Overexpression of TREK-1 caused CHO cells arresting at the G1 phase, and significantly decreased the expression of cyclin D1. The TREK-1 inhibitor l-butylphthalide (1-100 MUmol/L) dose-dependently attenuated TREK-1-induced G1 phase cell arrest. Moreover, overexpression of TREK 1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element-binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180/Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3). CONCLUSION: TREK-1 overexpression suppresses CHO cell proliferation by inhibiting the activity of PKA and p38/MAPK signaling pathways and subsequently inducing G1 phase cell arrest. PMID- 27397545 TI - Superstructure formation in SrBa8[BN2]6 and EuBa8[BN2]6. AB - X-ray pure samples of SrBa8[BN2]6 and EuBa8[BN2]6 were synthesized from appropriate amounts of binary nitrides (Sr3N2, Ba3N2 and BN in sealed niobium ampoules and EuN, Ba3N2 and BN in BN crucibles, respectively) at temperatures up to 1370 K. The structure of SrBa8[BN2]6 was refined from single crystal X-ray diffractometer data: Fd3[combining macron]m, a = 1595.1(1) pm, wR(F(2)) = 0.0515, 387 F(2) values and 21 variables. EuBa8[BN2]6 has a lattice parameter of 1595.00(9) pm. Both nitridoborates adopt a new 2 * 2 * 2 superstructure variant of the LiCa4[BN2]3 type, realized through ordering of vacancies and Sr(2+) and Eu(2+) cations, respectively. The structures of SrBa8[BN2]6 and LiCa4[BN2]3 are related by a group-subgroup scheme. The Sr(2+)/vacancy ordering leads to an asymmetric coordination (1 * Sr(2+) and 8 * Ba(2+) in a distorted, mono-capped square prism) for the [BN2](3-) units with B-N distances of 132 and 136 pm. Vibrational spectra of SrBa8[BN2]6 and EuBa8[BN2]6 confirm the discrete linear [BN2](3-) units and (11)B solid state MAS NMR spectra are compatible with single crystallographic sites for the boron atoms. In EuBa8[BN2]6 the spectra are profoundly influenced by interactions of the (11)B nuclei with the unpaired electrons of the paramagnetic Eu(2+) ions. PMID- 27397544 TI - Renal-targeting triptolide-glucosamine conjugate exhibits lower toxicity and superior efficacy in attenuation of ischemia/reperfusion renal injury in rats. AB - AIM: We previously reported a novel triptolide (TP)-glucosamine conjugate (TPG) that specifically accumulated in kidneys and protected renal function from acute ischemia/reperfusion (I/R) injury in rats. In this study we further examined the molecular mechanisms underlying the renoprotective action of TPG. METHODS: The renal-targeting of TPG was investigated in a human proximal renal tubular epithelial cell line (HK-2) by measuring cell uptake of TP or TPG. The effects of TP or TPG on cell cycle distribution and apoptosis rate of HK-2 cells were assessed, and the activities of caspase-3 and caspase-9 were also measured. SD rats were subjected to bilateral renal ischemia by temporarily clamping both renal pedicles. The rats were administered TP (4.17 MUmol.kg-1.d-1, iv) or TPG (4.17 MUmol.kg-1.d-1, iv) for 3 d before the renal surgery. The kidneys were harvested after 24 h of recovery from the surgery. The levels of oxidative stress, proinflammatory cytokines, chemotactic cytokines and intracellular adhesion molecules in kidneys were examined. RESULTS: The uptake of TPG in HK-2 cells was 2-3 times higher than that of TP at the concentrations tested. Furthermore, TPG targeting the proximal tubules was mediated through interactions with megalin receptors. TP (40-160 nmol/L) concentration-dependently increased G2/M arrest, apoptosis and caspase-3/caspase-9 activity in HK-2 cells, whereas the same concentrations of TPG did not show those features when compared with the control group. In I/R-treated rats, TPG administration caused more robust down regulation of proinflammatory cytokines (TNF-alpha, IL-6, IL-1, TGF-beta) and chemotactic cytokines (MCP-1) in the kidneys compared with TP administration, suggesting the inhibition of the proliferation and accumulation of lymphocytes. And TPG administration also caused more prominent inhibition on the levels of oxidative stress and intracellular adhesion molecules in the kidneys, compared with TP administration. CONCLUSION: The renal-targeting TPG is more effective and less toxic than TP, in amelioration of I/R-induced rat renal injury, which may provide a new avenue for the treatment of acute kidney injury. PMID- 27397546 TI - Standardisation or resilience? The paradox of stability and change in patient safety. AB - This article explores an apparent paradox of stability and change in patient safety thinking and practice. The dominant approach to patient safety has largely been focused on closing 'safety gaps' through standardisation in seemingly stable healthcare systems. However, the presupposition of system stability and predictability is presently being challenged by critics who insist that healthcare systems are complex and changing entities, thereby shifting focus towards the healthcare organisation's resilient and adaptive capacities. Based on a close reading of predominant patient safety literature, the article analyses how a separation between stability and change is articulated in ontological, historical, and situated terms, and it suggests the way in which predetermining healthcare settings as either stable or unstable paves the way for a system engineering approach to patient safety that pre-empts certain types of safety solutions. Drawing on John Dewey's influential ideas about the interconnectedness of stability and change, this prescriptive perspective is discussed and challenged. It is suggested that only by rethinking the relationship between change and stability can patient safety efforts begin to address the uncertainty of medical practice as well as the necessary competences of healthcare professionals to act with 'safety dispositions' as a precondition for delivering safe care. PMID- 27397547 TI - Evolutionary divergence of reaction norms in ecological context: a commentary. PMID- 27397548 TI - Blood concentration of prilocaine and lidocaine after the use of topical anesthesia (Oraqix(r) ) in lacerated wounds. AB - BACKGROUND/AIM: Soft tissue injuries have been reported as being sutured using only topical anesthesia applied in the laceration wound. The objective of this study was to assess the pharmacokinetic profile of components of Oraqix(r) (2.5% prilocaine and 2.5% lidocaine) when applied in a laceration as compared to intact skin application in the mouse. MATERIALS AND METHODS: A total of 200 BALB/c male mice were used in this study. The mice were divided into three groups: group A: shaved and laceration group (80 mice); B: shaved and intact skin group (80 mice); and C: control group (shaved, no treatment; 40 mice) which underwent the same procedures but without application of Oraqix(r) . Blood samples were collected over 90 min. Plasma sample analysis employing liquid chromatography coupled with the tandem mass spectrometric (LC-MS/MS) method was used to determine plasma concentrations of lidocaine and prilocaine. Pharmacokinetic analysis of mouse plasma concentrations was carried out by standard non-compartmental methods. RESULTS: Absorption of both lidocaine and prilocaine was rapid. Cmax and AUC values of lidocaine were significantly increased by fourfold and twofold, respectively, in lacerated mouse skin compared to intact skin. Similarly, prilocaine's Cmax and AUC values were also increased by 2.5-fold and fourfold, respectively, in lacerated skin compared to intact skin. CONCLUSION: When Oraqix(r) was applied directly into the skin laceration, the plasma concentration of lidocaine and prilocaine was significantly increased as compared to when applied on intact skin. The present study, albeit in mice, indicates that the plasma levels of lidocaine and prilocaine can reach very high levels when the thermosetting gel Oraqix(r) is placed directly in wounds. PMID- 27397549 TI - Transactional sex and the challenges to safer sexual behaviors: a study among male sex workers in Chennai, India. AB - Male sex workers (MSW) are a significant but invisible population in India who are at risk for HIV/sexually transmitted infections (STIs). Few studies from India have documented HIV risk factors and motivations for sex work in this population. Between 2013 and 2014, a community-based convenience sample of 100 MSW in Chennai (south India) completed a baseline risk assessment as part of a behavioral intervention. Participants were >=18 years, and reported current sex work. We report medians and proportions, and Wilcoxon-Mann-Whitney and chi-square tests are used to examine differences between sex work and sexual behavior measures by income source. Participants were engaged in sex work for 5.0 years (IQR = 2.3-10.0), and earned 3000 (IQR = 2000-8000) Rupees (<50 USD) per month from sex work. Sixty-four percent reported ever testing for HIV and 20.2% for any STI. The most common reasons for starting sex work were money (83.0%) and pleasure (56.0%). Compared to participants with an additional source of income, those whose only source of income was sex work reported more male clients in the past month (10.0 vs. 6.0, p = .017), as well as more condomless anal sex acts with male clients (8.0 vs. 5.0, p = .008). Nearly 70.0% were offered more money not to use a condom during sex with a client, and 74.2% reported accepting more money not to use a condom. Three-quarters reported having experienced difficulty using condoms with clients. MSW in India engage in high levels of sexual risk for HIV/STIs. Money appears to be a driving factor for engaging in sex work and condomless sex with clients. HIV prevention interventions with MSW should focus on facilitating skills that will support their ability to negotiate sexual safety in the context of monetary disincentives. PMID- 27397550 TI - Early childhood exposure to short periods of sevoflurane is not associated with later, lasting cognitive deficits. AB - BACKGROUND: A detrimental effect of commonly used anesthetics on the neurodevelopmental and behavioral parameters has long been shown in young animals subjected to early childhood anesthesia. Epidemiologic studies suggest the possibility of a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood. However, these results are still preliminary and inconclusive. AIM: To further elucidate the probability of occurrence of such adverse outcomes, we evaluated cognitive performance of children who underwent general anesthesia early in their childhood. METHOD: One hundred and fifteen children aged 5-16 years with established glaucoma were included in the study. Of these, 68 children had a history of at least one general anesthesia with sevoflurane before age 3. Phonemic and semantic verbal fluency, and forward and backward digit span tests were performed to evaluate cognitive function in the study subjects. RESULTS: The two-way anova revealed that all these variables showed significant changes in various age groups, but they were comparable among subjects with no, single, or multiple childhood anesthesia. CONCLUSION: It can be concluded that brief periods of anesthesia with single anesthetic sevoflurane may be safe for children under age 3. PMID- 27397551 TI - Epidemiology of invasive fungal infections during induction therapy in adults with acute lymphoblastic leukemia: a GRAALL-2005 study. AB - Little data have been published concerning invasive fungal infections during treatment of acute lymphoblastic leukemia (ALL). Patients included between May 2006 and October 2012 in the multicenter phase III trial for newly diagnosed ALL (GRAALL-2005) were retrospectively reviewed for the occurrence of IFI using the EORTC modified criteria. These patients did not routinely receive antifungal prophylaxis. Among 969 patients included (median age 47 years), 65 (6.7%) developed IFI during induction chemotherapy: 26 (3.3%) invasive aspergillosis (IA), 33 (3.4%) invasive candidiasis (IC) and six other IFI. For IA, the median time between induction therapy and IA diagnosis was 20 days. Diagnosis was probable in 22 cases and proven in four. Aspergillus antigen in serum was tested in all cases and positive in 24. Overall 12-week mortality after diagnosis of IA was 5/26 and attributable mortality related to the infection was 4/26 (15.4%). For IC, the median time between induction therapy and diagnosis was 19 days. Diagnosis was proven in 29 episodes. Candida albicans was the major pathogen in yeast infections (16/27). Overall 12-week mortality after diagnosis of IC was 8/33 (24.2%) and attributable mortality related to the infection was 7/33. The median delay between induction chemotherapy initiation and attributable death related to IC was 15 days. These findings may help to optimize the future management of ALL patients, and as in AML advocate systematic monitoring and the development of prophylactic or preemptive antifungal treatments. PMID- 27397552 TI - Chiral amino-phosphine and amido-phosphine complexes of Ir and Mg. Catalytic applications in olefin hydroamination. AB - The reactions of rac- and (S,S)-trans-9,10-dihydro-9,10-ethanoanthracene-11,12 diamine (ANDEN) with PClPh2 in the presence of NEt3 yield the chiral amino phosphine ligands rac-6 and (S,S)-6, respectively, on multi-gram scales. Both forms of 6 react quantitatively with MgPh2 to afford the C2-symmetric, N-bound Mg amidophosphine complexes rac-7 and (S,S)-7. The former crystallizes as a racemic conglomerate, which is a rare occurrence. Mixing (S,S)- or rac-6 with [IrCl(COE)2]2 leads in both cases to the homochiral dinuclear chloro-bridged P ligated aminophosphine iridium complexes (S,S,S,S)-9 and rac-9 in excellent yields. X-ray quality single crystals only grow as the racemic compound (or 'true racemate') rac-9 thanks to its lowered solubility. In the coordinating solvent CH3CN, rac-9 transforms in high yield into mononuclear Ir-complex rac-10. The crystal structures of compounds rac-6, (S,S)-7, rac-9, and rac-10 reveal the ambidentate nature of the P-N function: amide-coordination in the Mg-complex (S,S)-7 and P-chelation of the softer Ir(i) centres in complexes rac-9 and rac 10. Furthermore, the crystal structures show flexible, symmetry lowering seven membered P-chelate rings in the Ir complexes and a surprising amount of deformation within the ANDEN backbone. The simulation of this deformation by DFT and SCF calculations indicates low energy barriers. (S,S)-7 and (S,S,S,S)-9 catalyze the intra- and intermolecular hydroamination of alkenes, respectively: 5 mol% of (S,S)-7 affords 2-methyl-4,4'-diphenylcyclopentyl amine quantitatively (7% ee), and 2.5 mol% of (S,S,S,S)-9 in the presence of 5.0 mol% co-catalyst (LDA, PhLi, or MgPh2) gives exo-(2-arylamino)bornanes in up to 68% yield and up to 16% ee. PMID- 27397553 TI - Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: a meta-analysis. AB - To identify risk factors for periprosthetic joint infection following primary total joint arthroplasty, a systematic search was performed in Pubmed, Embase and Cochrane library databases. Pooled odds ratios (ORs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Patient characteristics, surgical-related factors and comorbidities, as potential risk factors, were investigated. The main factors associated with infection after total joint arthroplasty (TJA) were male gender (OR, 1.48; 95% CI, 1.19-1.85), age (SMD, -0.10; 95% CI, -0.17--0.03), obesity (OR, 1.54; 95% CI, 1.25-1.90), alcohol abuse (OR, 1.88; 95% CI, 1.32-2.68), American Society of Anesthesiologists (ASA) scale > 2 (OR, 2.06; 95% CI, 1.77-2.39), operative time (SMD, 0.49; 95% CI, 0.19-0.78), drain usage (OR, 0.36; 95% CI, 0.18-0.74), diabetes mellitus (OR, 1.58; 95% CI, 1.37-1.81), urinary tract infection (OR, 1.53; 95% CI, 1.09-2.16) and rheumatoid arthritis (OR, 1.57; 95% CI, 1.30-1.88). Among these risk factors, ASA score > 2 was a high risk factor, and drain usage was a protective factor. There was positive evidence for some factors that could be used to prevent the onset of infection after TJA. PMID- 27397554 TI - Herbal Medicines in Idiopathic Heavy Menstrual Bleeding: A Systematic Review. AB - Idiopathic heavy menstrual bleeding (HMB; IHMB) is a common gynecological problem with no pelvic pathology or general bleeding disorder. Herbal remedies are commonly used to treat HMB. This systematic review aimed to assess the effectiveness and safety of herbal preparations for the treatment of IHMB. MEDLINE, Ovid, and the Cochrane Central Register of Controlled Trials were searched from inception to 23 August 2015. Only randomized controlled trials were considered. Three randomized controlled trials were included in this systematic review. Different herbal preparations were used in the included trials. In two studies, Ginger capsules and myrtle fruit syrup significantly reduced the menstrual duration and blood loss compared with placebo based on the pictorial blood loss assessment chart score (p < 0.001, p = 0.01). In another trial, Punica granatum flower capsules were as effective as tranexamic acid capsules in reducing the mean (SD) pictorial blood loss assessment chart score, with no significant difference between the two treatments (p = 0.3). The results show that the methods used in these trials may reduce menstrual bleeding in women with IHMB. Additional well-designed trials are needed to investigate the safety and efficacy of herbs for the treatment of women with IHMB or other forms of HMB. PMID- 27397555 TI - Membrane activity of a supramolecular peptide-based chemotherapeutic enhancer. AB - Self-assembly of de novo designed multidomain peptides (MDPs) resulted in functional membrane-active supramolecular nanofibers. The membrane activity was analyzed through fluorescence membrane localization and patch-clamp electrophysiology yielding important information that can be used for the development of a new type of supramolecular peptide-based chemotherapeutic enhancer. PMID- 27397556 TI - High contaminant loads in Lake Apopka's riparian wetland disrupt gene networks involved in reproduction and immune function in largemouth bass. AB - Lake Apopka (FL, USA) has elevated levels of some organochlorine pesticides in its sediments and a portion of its watershed has been designated a US Environmental Protection Agency Superfund site. This study assessed reproductive endpoints in Florida largemouth bass (LMB) (Micropterus salmoides floridanus) after placement into experimental ponds adjacent to Lake Apopka. LMB collected from a clean reference site (DeLeon Springs) were stocked at two periods of time into ponds constructed in former farm fields on the north shore of the lake. LMB were stocked during early and late oogenesis to determine if there were different effects of contamination on LMB that may be attributed to their reproductive stage. LMB inhabiting the ponds for ~4months had anywhere from 2 to 800 times higher contaminant load for a number of organochlorine pesticides (e.g. p, p' DDE, methoxychlor) compared to control animals. Gonadosomatic index and plasma vitellogenin were not different between reproductively-stage matched LMB collected at reference sites compared to those inhabiting the ponds. However, plasma 17beta-estradiol was lower in LMB inhabiting the Apopka ponds compared to ovary stage-matched LMB from the St. Johns River, a site used as a reference site. Sub-network enrichment analysis revealed that genes related to reproduction (granulosa function, oocyte development), endocrine function (steroid metabolism, hormone biosynthesis), and immune function (T cell suppression, leukocyte accumulation) were differentially expressed in the ovaries of LMB placed into the ponds. These data suggest that (1) LMB inhabiting the Apopka ponds showed disrupted reproduction and immune responses and that (2) gene expression profiles provided site-specific information by discriminating LMB from different macro habitats. PMID- 27397557 TI - Hogfish Lachnolaimus maximus (Labridae) confirmed in the south-western Atlantic Ocean. AB - Based on material deposited in collections, photographic records and other reports from fishermen and divers, the occurrence of the hogfish Lachnolaimus maximus (Labridae) is confirmed in the south-western Atlantic Ocean, near the Brazilian coast as far south as southern Brazil. The recognized range of this species should therefore be extended c. 3000 km further south. PMID- 27397558 TI - Plant protection product residues in white grapes and wines of "Malvasia Istriana" produced in Istria. AB - Monitorting of plant protection product residues was performed in 12 grape and 66 wine samples of "Malvasia Istriana" variety, produced in Istria winegrowing region of Croatia and Slovenia. The samples were analysed for the presence of 169 different active compounds using two multiresidual analytical methods: gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry. Residues were found in 58.3% of all the inspected grape samples and in 28.8% of all the inspected wine samples. Beside that contents of residues in grapes were below 10% of maximum residue level values and they should not represent any risk for "Malvasia Istriana" grape or wine consumers. PMID- 27397559 TI - Catalytic cascade aldol-cyclization of tertiary ketone enolates for enantioselective synthesis of keto-esters with a C-F quaternary stereogenic center. AB - The first asymmetric catalytic aldol-cyclization reaction of detrifluoroacetylatively in situ generated enolates with methyl 2-formylbenzoate is reported. This reaction tolerates a wide range of substrates, affording fluorinated quaternary stereogenic alpha,alpha-dialkyl/cyclo-alkyl-beta ketoesters with good yields, high diastereo- (94% de) and enantioselectivity (96% ee) at room temperature. PMID- 27397560 TI - Onset of Impaired Sleep and Cardiovascular Disease Risk Factors: A Longitudinal Study. AB - STUDY OBJECTIVES: Impaired sleep has been linked to increased risk of cardiovascular disease (CVD), but the underlying mechanisms are still unsettled. We sought to determine how onset of impaired sleep affects the risk of established physiological CVD risk factors (i.e., hypertension, diabetes, and dyslipidemia). METHODS: In a longitudinal cohort study with 3 survey waves (2000, 2004, 2008) from the Finnish Public Sector study we used repeated information on sleep duration and disturbances to determine onset of impaired sleep. Information on development of CVD risk factors, as indicated by initiation of medication for hypertension, diabetes, and dyslipidemia was derived from electronic medical records within 8 years of follow-up. Data on 45,647 participants was structured as two data-cycles to examine the effect of change in sleep (between two waves) on incident CVD events. We applied strict inclusion and exclusion criteria to determine temporality between changes in sleep and the outcomes. RESULTS: While we did not find consistent effects of onset of short or long sleep, we found onset of disturbed sleep to predict subsequent risk of hypertension (hazard ratio = 1.22, 95% CI: 1.04-1.44) and dyslipidemia (HR = 1.17, 95% CI: 1.07-1.29) in fully adjusted analyses. CONCLUSIONS: Results suggest that onset of sleep disturbances rather than short or long sleep mark an increase in physiological risk factors, which may partly explain the higher risk of CVD observed among impaired sleepers. COMMENTARY: A commentary on this paper appears in this issue on page 1629. PMID- 27397561 TI - Sleep Duration and White Matter Quality in Middle-Aged Adults. AB - STUDY OBJECTIVES: Sleep duration has been associated with risk of dementia and stroke, but few studies have investigated the relationship between sleep duration and brain MRI measures, particularly in middle age. METHODS: In a prospective cohort of 613 black and white adults (mean age = 45.4 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, participants reported typical sleep duration, dichotomized into moderate sleep duration (> 6 to <= 8 h) and short sleep duration (<= 6 h) at baseline (2005-2006). Five years later, we obtained brain MRI markers of white matter including fractional anisotropy, mean diffusivity, and white matter hyperintensities. RESULTS: Compared to moderate sleepers, short sleepers had an elevated ratio of white matter hyperintensities to normal tissue in the parietal region (OR = 2.31, 95% CI: 1.47, 3.61) adjusted for age, race/sex, education, hypertension, stroke/TIA, depression, smoking status, and physical activity. White matter diffusivity was also higher, approximately a 0.2 standard deviation difference, in frontal, parietal, and temporal white matter regions, among those reporting shorter sleep duration in (P < 0.05 for all). CONCLUSIONS: Short sleep duration was associated with worse markers of white matter integrity in midlife. These mid-life differences in white matter may underlie the link between poor sleep and risk of dementia and stroke. PMID- 27397562 TI - A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine. AB - STUDY OBJECTIVES: Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. METHODS: We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). RESULTS: The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. CONCLUSIONS: The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. PMID- 27397563 TI - Normoxic Recovery Mimicking Treatment of Sleep Apnea Does Not Reverse Intermittent Hypoxia-Induced Bacterial Dysbiosis and Low-Grade Endotoxemia in Mice. AB - STUDY OBJECTIVES: Intermittent hypoxia (IH) mimicking obstructive sleep apnea (OSA) significantly modifies gut microbiota in mice. However, whether these IH induced gut microbiome changes are reversible after restoring normal oxygenation (the equivalent of effective OSA therapy) is unknown. The aim of this study was to investigate gut microbiota composition and circulating endotoxemia after a post-IH normoxic period in a mouse model of OSA. METHODS: Ten mice were subjected to IH (40 sec 21% O2-20 sec 5% O2) for 6 h/day for 6 w and 10 mice breathing normoxic air (NM) were used as controls. After exposures, both groups were subjected to 6 w in normoxia. Microbiome composition of fecal samples was determined by 16S ribosomal RNA (rRNA) pyrosequencing. Bioinformatic analysis was performed by Quantitative Insights into Microbial Ecology. Plasma lipopolysaccharide (LPS) levels were measured by endotoxin assay. RESULTS: After normoxic recovery, the Chao and Shannon indices of each group suggested similar bacterial richness and diversity. 16S rRNA pyrosequencing analysis showed that IH exposed mice had a significant decrease in the abundance of Bacteroidetes and a significant increase of Firmicutes and Deferribacteres compared to the NM group. After normoxic recovery, circulating LPS concentrations were higher in the IH group (P < 0.009). Moreover, the IH group showed a negative and significant correlation between the abundance of Lactobacillus and Ruminococcus and significant positive correlations between the abundance of Mucispirillum and Desulfovibrio and plasma LPS levels, respectively. CONCLUSIONS: Even after prolonged normoxic recovery after IH exposures, gut microbiota and circulating endotoxemia remain negatively altered, suggesting that potential benefits of OSA treatment for reversing OSA-induced changes in gut microbiota may either require a longer period or alternative interventions. PMID- 27397564 TI - The Boom in Wearable Technology: Cause for Alarm or Just What is Needed to Better Understand Sleep? PMID- 27397565 TI - WEIRD Considerations When Studying Adolescent Sleep Need. PMID- 27397566 TI - The Role of Obstructive Sleep Apnea in Cognitive Dysfunction in Multiple Sclerosis. PMID- 27397567 TI - Management and Risk Reduction of Rheumatoid Arthritis in Individuals with Obstructive Sleep Apnea: A Nationwide Population-Based Study in Taiwan. AB - STUDY OBJECTIVES: To explore associations between obstructive sleep apnea (OSA) and autoimmune diseases and evaluate whether OSA management reduces the incidence of autoimmune diseases. METHODS: This was a retrospective cohort study using nationwide database research. The data was from 105,846 adult patients in whom OSA was diagnosed and recorded in the Taiwan National Health Insurance Research Database between 2002 and 2011 were the patients were analyzed retrospectively. Patients with antecedent autoimmune diseases were excluded. A comparison cohort of 423,384 participants without OSA served as age- and sex-matched controls. Multivariable Cox regression analysis was performed on both cohorts to compute risk of autoimmune diseases during follow-up. Time-dependent OSA treatment effect was analyzed among patients with OSA. There were no interventions. RESULTS: Among patients with OSA, overall risk for incident autoimmune diseases was significantly higher than that in controls (adjusted hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.66-2.27). Risk for individual autoimmune diseases, including rheumatoid arthritis (RA), Sjogren syndrome (SS), and Behcet disease, was significantly higher in patients with OSA than in controls (HRs [95% CI]: RA 1.33 [1.03-1.72, SS 3.45 [2.67-4.45] and Behcet disease 5.33 [2.45 12.66]). Increased risk for systemic lupus erythematosus (HR 1.00 [0.54-1.84]) and systemic sclerosis (HR 1.43 [0.51-3.96]) did not reach statistical significance. Patients with OSA receiving treatment had an overall reduced risk of RA and other autoimmune diseases (time-dependent HRs [95% CI]: 0.22 [0.05 0.94] and 0.51 [0.28-0.92], respectively). CONCLUSIONS: Patients with OSA are associated with higher risk for developing RA, SS, and Behcet disease. OSA management is associated with reduced risk of RA. PMID- 27397568 TI - Spatiotemporal Organization and Cross-Frequency Coupling of Sleep Spindles in Primate Cerebral Cortex. AB - STUDY OBJECTIVES: The sleep spindle has been implicated in thalamic sensory gating, cortical development, and memory consolidation. These multiple functions may depend on specific spatiotemporal emergence and interactions with other spindles and other forms of brain activity. Therefore, we measured sleep spindle cortical distribution, regional heterogeneity, synchronization, and phase relationships with other electroencephalographic components in freely moving primates. METHODS: Transcortical field potentials were recorded from Japanese monkeys via telemetry and were analyzed using the Hilbert-Huang transform. RESULTS: Spindle (12-20 Hz) current sources were identified over a wide region of the frontoparietal cortex. Most spindles occurred independently in their own frequency, but some appeared concordant between cortical areas with frequency interdependence, particularly in nearby regions and bilaterally symmetrical regions. Spindles in the dorsolateral prefrontal cortex appeared around the surface-positive and depth-negative phase of transcortically recorded slow oscillations (< 1 Hz), whereas centroparietal spindles emerged around the opposite phase. The slow-oscillation phase reversed between the prefrontal and central regions. Gamma activities increased before spindle onset. Several regional heterogeneities in properties of human spindles were replicated in the monkeys, including frequency, density, and inter-cortical time lags, although their topographic patterns were different from those of humans. The phase amplitude coupling between spindle and gamma activity was also replicated. CONCLUSIONS: Spindles in widespread cortical regions are possibly driven by independent rhythm generators, but are temporally associated to spindles in other regions and to slow and gamma oscillations by corticocortical and thalamocortical pathways. PMID- 27397569 TI - Restricting Time in Bed in Early Adolescence Reduces Both NREM and REM Sleep but Does Not Increase Slow Wave EEG. AB - STUDY OBJECTIVES: School night total sleep time decreases across adolescence (9 18 years) by 10 min/year. This decline is comprised entirely of a selective decrease in NREM sleep; REM sleep actually increases slightly. Decreasing sleep duration across adolescence is often attributed to insufficient time in bed. Here we tested whether sleep restriction in early adolescence produces the same sleep stage changes observed on school nights across adolescence. METHODS: All-night sleep EEG was recorded in 76 children ranging in age from 9.9 to 14.0 years. Each participant kept 3 different sleep schedules that consisted of 3 nights of 8.5 h in bed followed by 4 nights of either 7, 8.5, or 10 h in bed. Sleep stage durations and NREM delta EEG activity were compared across the 3 time in bed conditions. RESULTS: Shortening time in bed from 10 to 7 hours reduced sleep duration by approximately 2 hours, roughly equal to the decrease in sleep duration we recorded longitudinally across adolescence. However, sleep restriction significantly reduced both NREM (by 83 min) and REM (by 47 min) sleep. Sleep restriction did not affect NREM delta EEG activity. CONCLUSIONS: Our findings suggest that the selective NREM reduction and the small increase in REM we observed longitudinally across 9-18 years are not produced by sleep restriction. We hypothesize that the selective NREM decline reflects adolescent brain maturation (synaptic elimination) that reduces the need for the restorative processes of NREM sleep. PMID- 27397570 TI - Genetic Correlation Analysis Suggests Association between Increased Self-Reported Sleep Duration in Adults and Schizophrenia and Type 2 Diabetes. AB - STUDY OBJECTIVES: We sought to examine how much of the heritability of self report sleep duration is tagged by common genetic variation in populations of European ancestry and to test if the common variants contributing to sleep duration are also associated with other diseases and traits. METHODS: We utilized linkage disequilibrium (LD)-score regression to estimate the heritability tagged by common single nucleotide polymorphisms (SNPs) in the CHARGE consortium genome wide association study (GWAS) of self-report sleep duration. We also used bivariate LD-score regression to investigate the genetic correlation of sleep duration with other publicly available GWAS datasets. RESULTS: We show that 6% (SE = 1%) of the variance in self-report sleep duration in the CHARGE study is tagged by common SNPs in European populations. Furthermore, we find evidence of a positive genetic correlation (rG) between sleep duration and type 2 diabetes (rG = 0.26, P = 0.02), and between sleep duration and schizophrenia (rG = 0.19, P = 0.01). CONCLUSIONS: Our results show that increased sample sizes will identify more common variants for self-report sleep duration; however, the heritability tagged is small when compared to other traits and diseases. These results also suggest that those who carry variants that increase risk to type 2 diabetes and schizophrenia are more likely to report longer sleep duration. PMID- 27397571 TI - Interaction between Obstructive Sleep Apnea and Shortened Telomere Length on Brain White Matter Abnormality. AB - STUDY OBJECTIVES: Age-related brain white matter changes (WMC) have been associated separately with obstructive sleep apnea (OSA) and short telomere length (TL). No studies have examined their interaction effect on WMC. METHODS: This is a cross-sectional study with a community-based sample of 420 participants (mean age, 61.3 +/- 7.2) from the Korean Genome and Epidemiology Study during 2011-2012. An overnight fasted blood sample was taken to determine glucose and blood lipid levels at the sleep laboratory of Korea University Ansan Hospital. The status of brain WMC was determined using structural magnetic resonance imaging at 1.5 Tesla. Overnight polysomnography was performed, and leukocyte TL was measured. OSA was determined based on apnea-hypopnea index, and short TL was defined as the lowest quartile of the study participants. RESULTS: Adjusting for age, sex, BMI, smoking, drinking, snoring, and hypertension, odds ratio (OR) of brain WMC was estimated using multivariate logistic regression. The odds ratio was significant for cardiovascular disease (OR, 4.5; 95% CI, 1.2-16.3) and OSA (OR, 4.0; 95% CI, 1.0-15.2) among those with short TL; and for diabetes (OR, 3.0; 95% CI, 1.3-13.0) and age (OR, 1.1; 95% CI, 1.0-1.1) among those with longer TL. Interaction effect of OSA and short TL (OR, 4.3; 95% CI, 1.4-13.8) was significant, compared to those with neither OSA nor short TL. CONCLUSIONS: This study provides a first evidence of mediated interaction of short TL with OSA on brain WMC in a community-based sample. The results generate new hypotheses regarding mechanisms of impaired brain health in sleep apnea. PMID- 27397572 TI - Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy. AB - STUDY OBJECTIVES: Narcolepsy with cataplexy (NC) is a chronic neurological disorder thought to result from an altered immune response based on a genetic predisposition coupled with environmental factors. Pandemrix vaccination has been reported to increase the risk of narcolepsy. We aimed at identifying other vaccines associated with the onset of narcolepsy. METHODS: Case series and retrospective database study. RESULTS: We identified four cases of NC following a tick-borne encephalitis (TBE) vaccination with FSME Immun. Additional four cases could be detected in the database of the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines in Germany. CONCLUSIONS: Our findings implicate TBE vaccination as a potential additional environmental factor for the development of NC and add additional evidence for an immunological mechanism in the pathogenesis of the disease. PMID- 27397573 TI - Assignment of the Fundamental Modes of Hydroxyacetone Using Gas-Phase Infrared, Far-Infrared, Raman, and ab Initio Methods: Band Strengths for Atmospheric Measurements. AB - Hydroxyacetone (acetol) is a simple organic molecule of interest in both the astrophysical and atmospheric communities. It has recently been observed in biomass burning events and is a known degradation product of isoprene oxidation. However, its vibrational assignment has never been fully completed, and few quantitative data are available for its detection via infrared spectroscopy. Our recent acquisition of both the pressure-broadened gas-phase data and the far-IR spectra now allow for unambiguous assignment of several (new) bands. In particular, the observed C-type bands of several fundamentals (particularly in the far-infrared) and a few combination bands demonstrate that the monomer is in a planar (Cs) conformation, at least a majority of the time. As suggested by other researchers, the monomer is a cis-cis conformer stabilized by an intramolecular O-H...O?C hydrogen bond forming a five-membered planar ring structure. Band assignments in the Cs point group are justified (at least for a good fraction of the molecules in the ensemble) by the presence of the C-type bands. The results and band assignments are well confirmed by both ab initio MP2 ccpvtz calculations and GAMESS (B3LYP) theoretical calculations. In addition, using vetted methods for quantitative measurements, we report the first IR absorption band strengths of acetol (also in electronic format) that can be used for atmospheric monitoring and other applications. PMID- 27397574 TI - Correlations among stimuli affect stimulus matching and stimulus liking. AB - Human subjects were exposed to AB, AC stimulus pairs and then to matching-to sample tests of stimulus equivalence (B-A, C-A, B-C, C-B) or to a task in which stimulus compounds (BA, CA, BC, CB) were rated for attractiveness. Matching-to sample tests revealed emergent B-A, C-A, B-C, and C-B choices, replicating previous results in the literature. The mean proportion of correct, emergent choices increased as a function of exposure to the AB, AC pairs. On the rating task, the liking scores of all stimulus compounds also increased as a function of exposure to the AB, AC pairs. After limited exposure to these pairs, however, the liking scores of the BC and CB compounds were negative. These findings are discussed in relation to perceptual and associative perspectives on the behavioral effects of stimulus correlations. PMID- 27397575 TI - Differential participation in cognitive tests is driven by personality, sex, body condition and experience. AB - Failure to participate in a cognitive test may result in sampling biases when measuring inter-individual variation in cognitive performances in both captive and wild populations. This would be problematic if particular classes of individuals consistently fail to participate, skewing data and making generalisations or comparisons difficult. We presented 144 pheasant chicks, raised under standardised conditions, with a battery of cognitive tests to investigate whether sex, body condition or personality traits, measured by differences in latencies to explore a novel object, novel environment or unknown conspecific, predicted individual variation in voluntary participation across 37 test sessions. In general, participation increased across testing sessions, yet patterns of participation differed with sex and body condition. Males with a high body condition were more likely to participate in early test sessions compared to males with a low body condition or females. While participation among males in high body condition was consistent across sessions, males with a low body condition and females, regardless of body condition, were more likely to participate in later, rather than earlier sessions. Individuals also showed repeatable behaviours across time and different contexts, revealing not only that the exploration of novelty, but also that the order that subjects entered the testing arena and their latencies to acquire a freely available meal-worm reward may be considered valid proxies for different personality traits. During each test session, those individuals that were among the first to voluntarily enter the testing arena were more likely to participate in subsequent trials. Moreover, when isolated in the testing arena, individuals that rapidly acquired a freely available meal-worm, positioned on the testing apparatus, were also more likely to participate in a cognitive test. Our findings therefore reveal that sex, body condition and personality traits, along with habituation to the testing paradigms, all play important roles in determining whether or not particular individuals participate in cognitive tests. Sampling biases may therefore misrepresent our understanding of variation in cognitive performance in wild and captive populations, making individual differences in cognition difficult to interpret. PMID- 27397576 TI - Incidence of Second Malignancies of Chronic Myeloid Leukemia During Treatment With Tyrosine Kinase Inhibitors. AB - BACKGROUND: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) by providing patients with long-term survival. Although most patients who receive TKI treatment have shown satisfactory tolerance, second malignancies (SMs) should not be ignored because of lifetime treatment. We designed a retrospective study to evaluate the incidence and possible risk factors of SMs in CML patients treated with TKIs. PATIENTS AND METHODS: Records of 223 patients with Philadelphia chromosome-positive CML treated with imatinib were reviewed to investigate frequencies and characteristics of SMs. The data of SMs were compared with the number expected from the National Central Cancer Registry. The possible risk factors of SM in CML patients treated with TKIs were also evaluated using Poisson regression in this study. RESULTS: After a median follow-up of 64 months (range, 4-253 months) from CML diagnosis, 7 patients (3.14%) developed 6 different SMs including colon, stomach, breast, kidney, cervical, and lymphonodus tissue. The risk of second cancer was higher than expected (observed-to-expected ratio, 2.45; 95% confidence interval, 1.17-5.14; P = .018). No associated elements were found in terms of influencing the incidence of SM in CML patients treated with TKIs. CONCLUSION: We found patients with CML treated with TKIs had a higher relative incidence of SM compared with the expected incidence among the general Chinese population. However, the correlations between second cancer and the potential risk factors including the length of exposure and cumulative dose of TKIs were not found in this study. PMID- 27397577 TI - Progression of small vessel disease correlates with cortical thinning in Parkinson's disease. AB - OBJECTIVE: Cerebral small-vessel disease (SVD) is a risk factor for dementia in Parkinson's disease (PD), however the pathophysiological role of SVD in PD dementia is unclear. We investigated the impact of baseline and progression of SVD on cortical thickness and the correlation to cognition. METHODS: Seventy three mild PD patients with baseline and follow-up structural MRI scans, serial clinical and neuropsychological assessments were studied. SVD included the load of white matter hyperintensities (WMH), lacunes and perivascular spaces (PVS). WMH progression was assessed using the modified Rotterdam Progression scale, while for lacunes and PVS, development of new lesions was considered as lesion progression. Patients were classified as having SVD-progression and SVD-no progression based on the longitudinal changes in their SVD measures. Freesurfer was used to measure baseline and follow-up regional cortical thickness and subcortical volumes and correlated to cognitive performance. RESULTS: Fourteen patients were classified as SVD-progression and 59 as SVD-no-progression. Over 18 months, PD SVD-progression demonstrated significant cortical thinning in the left frontal and bilateral parietal regions with associated decline in memory, executive function, and motor functions. PD SVD-progression also had reduced volumes in the nucleus accumbens and amygdala at baseline and greater atrophy in the caudate nucleus over 18 months. DISCUSSION: The extent and progression of SVD is associated with focal cerebral atrophy and domain-specific cognitive dysfunction. Measures to retard SVD may be potentially useful in preventing dementia in PD. PMID- 27397578 TI - Bordetella trematum sepsis with shock in a diabetic patient with rapidly developing soft tissue infection. AB - Bordetella is a gram-negative, glucose non-fermenting bacillus, consisting of many host-associated species. B. trematum has previously been identified in wound infections, but rarely known to be a source of bacteremia. Currently, 16S rRNA sequencing represents the reference standard method by which identification is made. Herein, we present a case of fatal B. trematum bacteremia with septic shock. The presumed primary site of the infection was a rapidly developing left leg deep soft tissue infection without necrotizing fasciitis. B. trematum should now be considered as a significant pathogen in sepsis. PMID- 27397579 TI - Macrophage NOS2 in Tumor Leukocytes. AB - SIGNIFICANCE: Leukocytes and especially macrophages are a major cellular constituent of the tumor mass. The tumor microenvironment not only determines their activity but in turn these cells also contribute to tumor initiation and progression. Recent Advances: Proinflammatory stimulated macrophages upregulate inducible nitric oxide synthase (NOS2) and produce high steady-state NO concentrations. NO provokes tumor cell death by initiating apoptosis and/or necrosis. Mechanisms may comprise p53 accumulation, immunestimulatory activities, and an increased efficacy of chemo- and/or radiotherapy. However, the potential cytotoxic activity of macrophages often is compromised in the tumor microenvironment and instead a protumor activity of macrophages dominates. Contributing factors are signals generated by viable and dying tumor cells, attraction and activation of myeloid-derived suppressor cells, and hypoxia. Limited oxygen availability not only attenuates NOS2 activity but also causes accumulation of hypoxia-inducible factors 1 and 2 (HIF-1/HIF-2). Activation of the HIF system is tightly linked to NO formation and affects the expression of macrophage phenotype markers that in turn add to tumor progression. CRITICAL ISSUES: To make use of the cytotoxic arsenal of activated macrophages directed against tumor cells, it will be critical to understand how, when, and where these innate immune responses are blocked and whether it will be possible to reinstall their full capacity to kill tumor cells. FUTURE DIRECTIONS: Low-dose irradiation or proinflammatory activation of macrophages in the tumor microenvironment may open options to boost NOS2 expression and activity and to initiate immunestimulatory features of NO that may help to restrict tumor growth. Antioxid. Redox Signal. 26, 1023-1043. PMID- 27397580 TI - Bone morphogenetic protein-induced cell differentiation involves Atg7 and Wnt16 sequentially in human stem cell-derived osteoblastic cells. AB - We established a differentiation method for homogeneous alpha7 integrin-positive human skeletal muscle stem cell (alpha7(+)hSMSC)-derived osteoblast-like cells with bone morphogenetic protein (BMP)-2. To explore the early signaling cascade for osteoblastic differentiation, we examined the upregulation of autophagy related gene (Atg) and wingless/int1 (Wnt) signaling during BMP-2-mediated human osteoblastic differentiation. In a screening experiment, BMP-2 increased the mRNA and protein levels of Atg7, Wnt16, and Lrp5/Fzd2 (a Wnt receptor), but not microtubule-associated protein 1 light chain (LC3; a mammalian homolog of yeast Atg8), TFE3, Beclin1, Atg5, Atg12, Wnt3a, or Wnt5, together with the amounts of autophagosomes and autophagy fluxes. Treatment with siRNAs against Atg7 and Wnt16 individually suppressed the BMP-2-induced increase in osteoblastic differentiation. The osteoblastic phenotype, involving osteocalcin (BGLAP), osteopontin (SPP1), and osterix (SP7) expression, decreased when autophagy was inhibited by chloroquine (an autophagy inhibitor), but increased after treatment with rapamycin (an autophagy enhancer). Taken together with our previous findings, we have revealed a unique sequential cascade of BMP-2->Atg7->Wnt16 >Lrp5/Fzd2->matrix metalloproteinase-13->osteoblastic differentiation. This cascade results in a potent increase in osteoblastic cell differentiation, indicating the unique involvement of Atg7, autophagy, and Wnt16 signaling in BMP 2-induced differentiation of alpha7(+)hSMSCs into osteoblast-like cells at a relatively early stage. PMID- 27397582 TI - Prevalence and correlates of prescription opioid residue injection. AB - BACKGROUND: There is growing evidence of intravenous administration of prescription opioids (POs) in several countries. Preparation of POs for injection may leave residues in containers and filters used by people who inject drugs and may lead to adverse health outcomes if they are injected. METHODS: This exploratory study used cross-sectional data from the COSMO study, a prospective cohort of out-of-treatment cocaine users carried out in Montreal (Canada) between October 2010 and August 2015. For this analysis, only one visit per participant was selected, that is, the first time the participant reported PO injection during the study. The outcome of interest, "injection of PO residues", was defined as having injected PO residues from a filter and/or a container in the last month. Correlates of this outcome were identified using logistic regression analyses. RESULTS: Of the 122 participants who reported PO injection during the study period, 41.8% had injected PO residues. Reporting an unstable source of income (AOR=4.26; 95% CI: 1.03-17.69), a recent overdose (AOR=5.45; 95% CI: 1.50 19.88) and a preponderant use of opiates (mostly opiate use versus other drugs excluding alcohol and cannabis) (AOR=2.46; 95% CI: 1.08-5.63) increased the risk of PO residue injection. The odds of reporting PO residue injection rose by 7% per unit increase in the score of psychological distress (AOR=1.07 per unit increase; 95% CI: 1.01-1.12). CONCLUSIONS: The findings of this study suggest that PO residue injection is associated with markers of vulnerability. Further investigation is needed in order to better understand this understudied drug injection practice. PMID- 27397581 TI - Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma. AB - YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. PMID- 27397583 TI - Evaluation of outer retinal tubulations in eyes switched from intravitreal ranibizumab to aflibercept for treatment of exudative age-related macular degeneration. AB - PURPOSE: To evaluate the changes of outer retinal tubulations (ORTs) as seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) where treatment was switched from intravitreal ranibizumab to intravitreal aflibercept. METHODS: This was a prospective study of eyes diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept, conducted at a single centre (Department of Ophthalmology at Pitie Salpetriere Hospital, Paris VI University) from January to July 2015. Before and after treatment was switched from ranibizumab to aflibercept, SD-OCT was used to evaluate the presence of ORTs. Additional assessments in this patient group included best-corrected visual acuity (BCVA), fluorescein angiography (FA), indocyanine green angiography (ICGA). Changes in pigment epithelium detachments (PED), presence of intraretinal cysts, and presence of subretinal fluid (SRF) were also noted. RESULTS: Twenty-four eyes of 24 consecutive patients (15 female/nine male, mean age 70 years) diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept were included in the analysis. After receiving aflibercept, patients were followed for a mean of 6.1 months. Prior to treatment switch, 97 % of eyes showed ORTs, while after treatment switch to aflibercept, at the end of the study period, 75 % had ORTs (p = 0.219). Changes in BCVA (LogMAR) were not statistically significant (1.16 +/- 0.44 to 1.18 +/- 1.06, p = 0.12), however, a significant reduction in central macular thickness (CMT) (from 406 MUm +/- 112 to 263 MUm +/- 68, p = 0.001), PED (from 70.8 % to 41.7 % , p = 0.016), presence of intraretinal cysts (from 83.3 % to 33.3 %, p = 0.002) and SRF (from 91.7 % to 25 %, p = 0.001 ) were noted. CONCLUSION: After switching from ranibizumab treatment to aflibercept, ORTs remained present in 75 % of eyes, and significant reductions in CMT, PED, and SRF, and presence of intraretinal cysts were observed. PMID- 27397584 TI - False Safety Behavior Elimination Therapy: A randomized study of a brief individual transdiagnostic treatment for anxiety disorders. AB - In response to the ever-growing number of CBT based therapy protocols, transdiagnostic approaches to anxiety treatment, based on models of anxiety emphasizing common elements across anxiety disorders, have been increasingly explored. The aim of the current study was to test the efficacy of an individually administered, brief (5-session) transdiagnostic treatment for anxiety disorders. The current treatment (called F-SET) focuses chiefly on the elimination of anxiety maintaining behaviors and cognitive strategies (so-called "safety" aids) among individuals suffering from a range of anxiety disorders including generalized anxiety disorder (GAD), social anxiety disorder (SAD) and panic disorder (PD). Patients (N=28; mean age=28.5years; 75% female; 71% White) were randomly assigned to F-SET or waitlist control conditions. Participants were assessed prior to, immediately after, and 1-month following treatment. In addition to independent assessments of diagnostic status, standardized self report measures and assessor ratings of severity and distress associated with anxiety symptoms were used. Participants in the F-SET condition experienced significantly less anxiety (Cohen's d=2.01) and depression (Cohen's d=2.16) than those in the WL condition. Mediational analysis showed that change in avoidance strategies mediated the group changes in anxiety symptoms. The results from the current study are an important first step in identifying a simpler, focused form of CBT that can be delivered with minimal therapist training, at a low cost and with minimal client contact time. PMID- 27397585 TI - Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution. AB - Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARgamma, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions. PMID- 27397586 TI - Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome. AB - BACKGROUND: A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is effective in treating irritable bowel syndrome (IBS). AIM: To compare the effects of gut-directed hypnotherapy to the low FODMAP diet on gastrointestinal symptoms and psychological indices, and assess additive effects. METHODS: Irritable bowel syndrome patients were randomised (computer generated list), to receive hypnotherapy, diet or a combination. Primary end point: change in overall gastrointestinal symptoms across the three groups from baseline to week 6. Secondary end-points: changes in psychological indices, and the durability of effects over 6 months. RESULTS: Of 74 participants, 25 received hypnotherapy, 24 diet and 25 combination. There were no demographic differences at baseline across groups. Improvements in overall symptoms were observed from baseline to week 6 for hypnotherapy [mean difference (95% CI): -33 (-41 to -25)], diet [-30 (-42 to -19)] and combination [-36 (-45 to -27)] with no difference across groups (P = 0.67). This represented >=20 mm improvement on visual analogue scale in 72%, 71% and 72%, respectively. This improvement relative to baseline symptoms was maintained 6 months post-treatment in 74%, 82% and 54%. Individual gastrointestinal symptoms similarly improved. Hypnotherapy resulted in superior improvements on psychological indices with mean change from baseline to 6 months in State Trait Personality Inventory trait anxiety of -4(95% CI -6 to -2) P < 0.0001; -1(-3 to 0.3) P = ns; and 0.3(-2 to 2) P = ns, and in trait depression of -3(-5 to -0.7) P = 0.011; -0.8(-2 to 0.2) P = ns; and 0.6(-2 to 3) P = ns, respectively. Groups improved similarly for QOL (all p <= 0.001). CONCLUSIONS: Durable effects of gut-directed hypnotherapy are similar to those of the low FODMAP diet for relief of gastrointestinal symptoms. Hypnotherapy has superior efficacy to the diet on psychological indices. No additive effects were observed. PMID- 27397588 TI - A Cost-Effectiveness Analysis of Clopidogrel for Patients with Non-ST-Segment Elevation Acute Coronary Syndrome in China. AB - INTRODUCTION: There are a number of economic evaluation studies of clopidogrel for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) published from the perspective of multiple countries in recent years. However, relevant research is quite limited in China. We aimed to estimate the long-term cost effectiveness for up to 1-year treatment with clopidogrel plus acetylsalicylic acid (ASA) versus ASA alone for NSTEACS from the public payer perspective in China. METHODS: This analysis used a Markov model to simulate a cohort of patients for quality-adjusted life years (QALYs) gained and incremental cost for lifetime horizon. Based on the primary event rates, adherence rate, and mortality derived from the CURE trial, hazard functions obtained from published literature were used to extrapolate the overall survival to lifetime horizon. Resource utilization, hospitalization, medication costs, and utility values were estimated from official reports, published literature, and analysis of the patient-level insurance data in China. To assess the impact of parameters' uncertainty on cost-effectiveness results, one-way sensitivity analyses were undertaken for key parameters, and probabilistic sensitivity analysis (PSA) was conducted using the Monte Carlo simulation. RESULTS: The therapy of clopidogrel plus ASA is a cost-effective option in comparison with ASA alone for the treatment of NSTEACS in China, leading to 0.0548 life years (LYs) and 0.0518 QALYs gained per patient. From the public payer perspective in China, clopidogrel plus ASA is associated with an incremental cost of 43,340 China Yuan (CNY) per QALY gained and 41,030 CNY per LY gained (discounting at 3.5% per year). PSA results demonstrated that 88% of simulations were lower than the cost effectiveness threshold of 150,721 CYN per QALY gained. Based on the one-way sensitivity analysis, results are most sensitive to price of clopidogrel, but remain well below this threshold. CONCLUSION: This analysis suggests that treatment with clopidogrel plus ASA for up to 1 year for patients with NSTEACS is cost effective in the local context of China from a public payers' perspective. FUNDING: Sanofi China. PMID- 27397587 TI - Sulodexide in Patients with Chronic Venous Disease of the Lower Limbs: Clinical Efficacy and Impact on Quality of Life. AB - INTRODUCTION: Chronic venous disease (CVD) of the lower limbs is a common problem. It is more prevalent in women than in men and has a significant impact on patients' quality of life (QoL) and on the healthcare system. The aim of this study was to evaluate the efficacy of sulodexide in adult patients with CVD of the lower limbs and its effect on patients' QoL. METHODS: Patients with CVD were treated with sulodexide [250 LSU (lipasemic units) twice daily] for 3 months in a setting of real-life clinical practice. The endpoints of this observational non comparative, open-label prospective study were the clinical efficacy of sulodexide (evaluated by scoring objective and subjective symptoms with a Likert type scale) and the impact of sulodexide therapy on patients' QoL [assessed using the chronic venous insufficiency quality of life questionnaire (CIVIQ)]. RESULTS: The study included 450 patients (mean age 46.9 +/- 10.5 years, range 17-78 years). A greater percentage of patients were female (65.4%). Three months of treatment with sulodexide significantly improved all objective and subjective symptoms (p < 0.0001). Overall, patients reported a significant improvement in all QoL scores (p < 0.0001). Adverse events were spontaneously reported by two patients (one case of epigastric pain and one of gastric pain with vomiting). CONCLUSION: Oral sulodexide significantly improves both objective and subjective symptoms, as well as functional and psychological aspects of QoL in patients with CVD. FUNDING: No funding or sponsorship was received for this study. Sponsorship for article processing charges and open access fees was provided by Alfa Wassermann. PMID- 27397589 TI - Assessment of Factors Related to the Understanding of Education and Knowledge of Self-Care among Patients with Diabetes Mellitus: A Cross-Sectional Prospective Study. AB - INTRODUCTION: The prevalence of diabetes mellitus is rapidly increasing particularly in developing countries. The aim of this study was to assess the knowledge and self-care practices of diabetes patients and to assess the contribution of the education to this knowledge level and glycemic control. METHODS: We formed patient groups consisting of 15-30 diabetic patients. First, patients were surveyed using a diabetes self-care knowledge questionnaire (DSCKQ 30). Sunsequently, a standard PowerPoint presentation about diabetes self management was made to the patients who were then surveyed again using DSCKQ-30. All patients were invited to hospital to measure their control glycated hemoglobin (HbA1c) level 3 months later. RESULTS: Of the total 364 participants, 62.9% were females. Significant increases in the percentage of correct responses were determined in all components between, before and after education. There was a significant decline of 1.1 in HbA1c levels after 3 months of education. Married or active working patients had a better understanding of the education about diabetes and had a greater knowledge of self-care management regardless of their level of education or income. CONCLUSION: Education about diabetes can significantly improve knowledge of self-care management and can help in achieving glycemic control. Continuing education about self-care management and complications is crucial and this should be accompanied by a regular assessment of pateients' diabetic knowledge. PMID- 27397591 TI - Better data, more tailored tuberculosis therapies. PMID- 27397592 TI - Nutrient distribution and structure affect the acidification of eutrophic ocean margins: A case study in southwestern coast of the Laizhou Bay, China. PMID- 27397590 TI - Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project. AB - BACKGROUND: Pyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available. METHODS: In a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system. FINDINGS: Pyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3.0-42.1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1.0-16.6% for ofloxacin, to 0.5-12.4% for levofloxacin, and 0.9-14.6% for moxifloxacin when tested at 0.5 MUg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 MUg/mL was low in all countries. INTERPRETATION: Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19-63% of patients with rifampicin-resistant tuberculosis. Even though the high level of resistance to ofloxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fluoroquinolones documented in all survey sites is an encouraging finding. Rational use of this class of antibiotics should therefore be ensured to preserve its effectiveness. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. PMID- 27397593 TI - Chemometric techniques in oil classification from oil spill fingerprinting. AB - Extended use of GC-FID and GC-MS in oil spill fingerprinting and matching is significantly important for oil classification from the oil spill sources collected from various areas of Peninsular Malaysia and Sabah (East Malaysia). Oil spill fingerprinting from GC-FID and GC-MS coupled with chemometric techniques (discriminant analysis and principal component analysis) is used as a diagnostic tool to classify the types of oil polluting the water. Clustering and discrimination of oil spill compounds in the water from the actual site of oil spill events are divided into four groups viz. diesel, Heavy Fuel Oil (HFO), Mixture Oil containing Light Fuel Oil (MOLFO) and Waste Oil (WO) according to the similarity of their intrinsic chemical properties. Principal component analysis (PCA) demonstrates that diesel, HFO, MOLFO and WO are types of oil or oil products from complex oil mixtures with a total variance of 85.34% and are identified with various anthropogenic activities related to either intentional releasing of oil or accidental discharge of oil into the environment. Our results show that the use of chemometric techniques is significant in providing independent validation for classifying the types of spilled oil in the investigation of oil spill pollution in Malaysia. This, in consequence would result in cost and time saving in identification of the oil spill sources. PMID- 27397594 TI - Pathological characteristics of low-risk papillary thyroid microcarcinoma with progression during active surveillance. AB - Papillary thyroid microcarcinoma (PTMC) is generally an indolent disease and active surveillance is conducted for low-risk cases. This study was carried out to clarify the pathological characteristics of PTMC cases that exhibited enlarged nodules or nodal metastasis during the surveillance period. A total of 188 PTMC cases that underwent surgery after active surveillance for >= 1 year were examined. Ki-67 labeling indices of > 5% and > 10% were detected in 50.0% and 22.2% of enlarged cases, respectively, values that were significantly higher than those in non-enlarged cases. Intraglandular dissemination and psammoma bodies in normal thyroid tissue were associated with new occurrence of nodal metastasis. Ultrasonographic macrocalcification and follicular variants were observed in 13.8% and 10.6% of non-enlarged cases, respectively, but not in enlarged or nodal metastatic cases. Intraglandular dissemination and psammoma bodies were ultrasonographically detected in 50.0% and 40.0% of cases, which was confirmed by microscopy. Thus, high Ki-67 labeling index, intraglandular metastasis, and psammoma bodies in normal thyroid tissue are indicators of progressive PTMC, and may be identified cytologically or ultrasonographically. In PTMC cases with ultrasonographic macrocalcification, active surveillance can be proactively implemented. PMID- 27397595 TI - RE: vital M, et al. Using the Female Sexual Function Index (FSFI) to evaluate sexual function in women with genital mutilation undergoing surgical reconstruction: a pilot prospective study. A rebuttal. PMID- 27397596 TI - Sezary Syndrome in a 17-Year-Old Boy: Clinicopathologic Features and Genomic Profile. AB - We describe the case of a 17-year-old Hispanic boy who had had erythroderma and diffuse lymphadenopathy for approximately 6 months. A diagnosis of Sezary syndrome was made on the basis of the histologic features of the skin; the presence of the same T-cell clone on the skin, blood, and bone marrow; and the high CD4(+) lymphocyte count with an aberrant phenotype in peripheral blood; bone marrow involvement was also present. The patient was treated with systemic gemcitabine and achieved partial remission. PMID- 27397597 TI - The M405V allele of the glutaryl-CoA dehydrogenase gene is an important marker for glutaric aciduria type I (GA-I) low excretors. AB - Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria resulting from a functional deficiency of glutaryl-CoA dehydrogenase, encoded by GCDH. Two clinically indistinguishable diagnostic subgroups of GA-I are known; low and high excretors (LEs and HEs, respectively). Early medical and dietary interventions can result in significantly better outcomes and improved quality of life for patients with GA-I. We report on nine cases of GA-I LE patients all sharing the M405V allele with two cases missed by newborn screening (NBS) using tandem mass spectrometry (MS/MS). We describe a novel case with the known pathogenic M405V variant and a novel V133L variant, and present updated and previously unreported clinical, biochemical, functional and molecular data on eight other patients all sharing the M405V allele. Three of the nine patients are of African American ancestry, with two as siblings. GCDH activity was assayed in six of the nine patients and varied from 4 to 25% of the control mean. We support the use of urine glutarylcarnitine as a biochemical marker of GA-I by demonstrating that glutarylcarnitine is efficiently cleared by the kidney (50 90%) and that plasma and urine glutarylcarnitine follow a linear relationship. We report the allele frequencies for three known GA-I LE GCDH variants (M405V, V400M and R227P) and note that both the M405V and V400M variants are significantly more common in the population of African ancestry compared to the general population. This report highlights the M405V allele as another important molecular marker in patients with the GA-I LE phenotype. Therefore, the incorporation into newborn screening of molecular screening for the M405V and V400M variants in conjunction with MS/MS could help identify asymptomatic at-risk GA-I LE patients that could potentially be missed by current NBS programs. PMID- 27397598 TI - 10-Year Trends in Serum Lipid Levels and Dyslipidemia Among Children and Adolescents From Several Schools in Beijing, China. AB - BACKGROUND: Serum lipid trends in children and adolescents are predictors of the future prevalence of cardiovascular disease in adults. METHODS: Data were obtained from cross-sectional studies conducted in 2004 and 2014. A total of 3249 children aged 6-18 years were included in the present study; serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured. RESULTS: Overall, upward trends in mean TC, non-HDL-C, and LDL-C levels, and in geometric mean TG levels, were observed (all P < 0.001). Mean HDL-C levels significantly decreased between 2004 and 2014 (from 1.54 mmol/L to 1.47 mmol/L; P < 0.001). The prevalence of abnormal levels of serum lipids, with the exception of the prevalence of low HDL-C (P = 0.503), significantly increased over the study period (all P < 0.05). The prevalence of hyperlipidemia (from 13.3%; 95% confidence interval [CI], 11.6%-15.0% to 24.5%; 95% CI, 22.4%-26.6%; P < 0.001) and dyslipidemia (from 18.8%; 95% CI, 16.9%-20.7% to 28.9%; 95% CI, 26.7%-31.3%; P < 0.001) also increased from 2004 to 2014. The prevalence of abnormal serum lipids increased, and mean serum lipid levels, with the exception of TC levels, worsened in subjects with obesity compared with non-overweight subjects, as well as in subjects with mixed obesity compared with non-obese subjects (P < 0.05 for all). CONCLUSIONS: Adverse trends in serum lipid concentrations over the past 10 years were observed among children aged 6-9 years, with the exception of specific lipids, and among adolescents aged 10-18 years, from several schools in Beijing, China. PMID- 27397599 TI - Influence of Adrenalectomy on Protective Effects of Urocortin I, a Corticotropin Releasing Factor, Against Indomethacin-Induced Enteropathy in Rats. AB - We examined the influence of adrenalectomy on NSAID-induced small intestinal damage in rats and investigated the possible involvement of adrenal glucocorticoids in the protective effects of urocortin I, a corticotropin releasing factor (CRF) agonist. Male SD rats without fasting were administered indomethacin s.c. and killed 24 h later in order to examine the hemorrhagic lesions that developed in the small intestine. Urocortin I (20 MUg/kg) was given i.v. 10 min before the administration of indomethacin. Bilateral adrenalectomy was performed a week before the experiment. Indomethacin (10 mg/kg) caused multiple hemorrhagic lesions in the small intestine, which were accompanied by a decrease in mucus secretion and increases in intestinal motility, enterobacterial invasion, and iNOS expression. Adrenalectomy markedly increased the ulcerogenic and motility responses caused by indomethacin, with further enhancements in bacterial invasion and iNOS expression; severe lesions occurred at 3 mg/kg, a dose that did not induce any damage in sham-operated rats. This worsening effect was also observed by the pretreatment with mifepristone (a glucocorticoid receptor antagonist). Urocortin I prevented indomethacin-induced enteropathy, and this effect was completely abrogated by the pretreatment with astressin 2B, a CRF2 receptor antagonist, but was not significantly affected by either adrenalectomy or the mifepristone pretreatment. These results suggested that adrenalectomy aggravated the intestinal ulcerogenic response to indomethacin, the intestinal hypermotility response may be a key element in the mechanism for this aggravation, and endogenous glucocorticoids played a role in intestinal mucosal defense against indomethacin-induced enteropathy, but did not account for the protective effects of urocortin I, which were mediated by the activation of peripheral CRF2 receptors. PMID- 27397601 TI - Hyperhaploid uterine mesenchymal tumors-a novel genetic subgroup? AB - Hyperhaploid karyotypes have been described to occur in subsets of various solid tumors and leukemias. In these cases, monosomy is noted for most of the chromosomes while a few chromosomes still remain disomic. Evidence has emerged that at least in some tumor entities these remaining chromosomes are non-randomly selected. In addition, structural alterations can accompany the reduced chromosome number and secondary duplication of the chromosome complement is also a frequent finding. In this report, we describe hyperhaploidy in a case of an endometrial stromal nodule of a 50 year old woman who underwent hysterectomy because of symptomatic uterine fibroids. In addition, we review two other recently described cases of uterine mesenchymal tumors with that type of genetic alteration. Despite some histologic differences, striking similarities between these three cases exist with respect to the chromosomes were retained as disomic. Thus, the question arises if hyperhaploidy defines a novel genetic subgroup of uterine mesenchymal tumors. PMID- 27397602 TI - Sleep Duration and Excessive Daytime Sleepiness Are Associated With Incidence of Disability in Community-Dwelling Older Adults. AB - OBJECTIVE: Although sleep disturbances are associated with disability among older adults, no longitudinal study has examined the impact of sleep assessed based on both sleep quality and quantity on incident disability. This study examined whether sleep duration and excessive daytime sleepiness were associated with incidence of disability in community-dwelling older adults. METHODS: A total of 4756 older adults (53.3% women, mean age 71.9 years) met the entry criteria for this study. We measured monthly incident disability, defined as the onset of being certified for personal support or care as required by Japanese public long term care insurance during the preceding 24 months. Sleep duration, excessive daytime sleepiness (EDS), and demographic factors were assessed at baseline. Cox's proportional hazard regression analysis estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of incidence of disability according to the 3 categories of sleep duration (short: <=6.0 hours, mid: 6.1 to 8.9 hours, long: >=9.0 hours), and we used mid duration sleepers as the reference group. RESULTS: Long sleep duration (HR 1.43, 95% CI 1.04-1.97) and presence of EDS (HR 1.41, 95% CI 1.01-1.98) were associated with higher rates of incident disability. Furthermore, a combination of sleep duration and EDS was associated with a higher rate of incident disability than the mid and no EDS group (HR 2.25, 95% CI 1.36 3.70). CONCLUSION: Long sleep duration and EDS affected the incident of disability; thus, older adults with both sleep patterns may require an intervention to alter their sleep habit. PMID- 27397600 TI - Rapid detection and subtyping of European swine influenza viruses in porcine clinical samples by haemagglutinin- and neuraminidase-specific tetra- and triplex real-time RT-PCRs. AB - BACKGROUND: A diversifying pool of mammalian-adapted influenza A viruses (IAV) with largely unknown zoonotic potential is maintained in domestic swine populations worldwide. The most recent human influenza pandemic in 2009 was caused by a virus with genes originating from IAV isolated from swine. Swine influenza viruses (SIV) are widespread in European domestic pig populations and evolve dynamically. Knowledge regarding occurrence, spread and evolution of potentially zoonotic SIV in Europe is poorly understood. OBJECTIVES: Efficient SIV surveillance programmes depend on sensitive and specific diagnostic methods which allow for cost-effective large-scale analysis. METHODS: New SIV haemagglutinin (HA) and neuraminidase (NA) subtype- and lineage-specific multiplex real-time RT-PCRs (RT-qPCR) have been developed and validated with reference virus isolates and clinical samples. RESULTS: A diagnostic algorithm is proposed for the combined detection in clinical samples and subtyping of SIV strains currently circulating in Europe that is based on a generic, M-gene specific influenza A virus RT-qPCR. In a second step, positive samples are examined by tetraplex HA- and triplex NA-specific RT-qPCRs to differentiate the porcine subtypes H1, H3, N1 and N2. Within the HA subtype H1, lineages "av" (European avian-derived), "hu" (European human-derived) and "pdm" (human pandemic A/H1N1, 2009) are distinguished by RT-qPCRs, and within the NA subtype N1, lineage "pdm" is differentiated. An RT-PCR amplicon Sanger sequencing method of small fragments of the HA and NA genes is also proposed to safeguard against failure of multiplex RT-qPCR subtyping. CONCLUSIONS: These new multiplex RT-qPCR assays provide adequate tools for sustained SIV monitoring programmes in Europe. PMID- 27397603 TI - Efficient Filtration of Effluent Organic Matter by Polycation-Clay Composite Sorbents: Effect of Polycation Configuration on Pharmaceutical Removal. AB - Hybrid polycation-clay composites, based on methylated poly vinylpyridinium, were optimized as sorbents for secondary effluent organic matter (EfOM) including emerging micropollutants. Composite structure was tuned by solution ionic strength and characterized by zeta potential, FTIR, X-ray diffraction, and thermal gravimetric analyses. An increase in ionic strength induced a transition from a train to a loops and tails configuration, accompanied by greater polycation adsorption. Composite charge reversal (zeta potential -18 to 45 mV) increased the adsorption of EfOM and humic acid (HA), moderately and sharply, respectively, suggesting electrostatic and also nonspecific interactions with EfOM. Filtration of EfOM by columns of positively charged composites was superior to that of granular activated carbon (GAC). The overall removal of EfOM was most efficient by the composite with a train configuration. Whereas a composite with a loops and tails configuration was beneficial for the removal of the anionic micropollutants diclofenac, gemfibrozil and ibuprofen from EfOM. These new findings suggest that the loops and tails may offer unique binding sites for small micropollutants which are overseen by the bulk EfOM. Furthermore, they may explain our previous observations that in the presence of dissolved organic matter, micropollutant filtration by GAC columns was reduced, while their filtration by composite columns remained high. PMID- 27397604 TI - Sustained efficacy of paclitaxel nanocrystals in hydrogel depot. PMID- 27397605 TI - Molecular Remodeling of the Insulin Receptor Pathway by Thiazolidinediones in Type 2 Diabetes Mellitus: A Brief Review. AB - Type 2 diabetes mellitus (T2DM) is characterized by abnormalities in carbohydrate, lipoprotein and lipid metabolism, leading to hyperglycemia and several other complications. Insulin is the major hormone regulating these facets by eliciting various biological responses through its receptor. Insulin exerts diverse effects on cells by targeting distinct functions such as gene expression, fatty acid synthesis, glucose transport and receptor translocation. Insulin mediates these effects through signaling pathways utilizing adapter molecules like small Gproteins, lipid and tyrosine kinases. The anomalous cell response in diabetic condition is due to altered expression/function of these molecules. Thiazolidinediones (TZD's), a class of oral hypoglycemic drugs, have shown to modify these responses, leading to insulin sensitizing effect(s). The TZD's are not only PPARgamma agonists, but substantial insulin sensitizing activity is observed through its direct and indirect targets of the insulin receptor pathway, which contributes to its overall performance. TZD's alter(s) cell response via downstream players, primarily IRS, Akt/PKB, PKC, GLUT4, MEK, ERK and transcription factor PGC1alpha. Thus, this review will focus on the alteration(s) of these molecules in various cell types in diabetic condition and their regulation by TZD's. The physiological changes that occur at the molecular level in T2DM and their modulation by TZD's will provide insights into the key players involved and the potential drug targets for future drug development. The review further highlights the key markers to be evaluated in screening of any potential anti-diabetic agent, and to standardize therapy for T2DM based upon its modulation of the various signaling pathways. PMID- 27397606 TI - Improving prognostic tools in systemic mastocytosis: Insights from mutations. PMID- 27397607 TI - White Adipose Tissue Browning: A Double-edged Sword. AB - The study of white adipose tissue (WAT) 'browning' has become a 'hot topic' in various acute and chronic metabolic conditions, based on the idea that WAT browning might be able to facilitate weight loss and improve metabolic health. However, this view cannot be translated into all areas of medicine. Recent studies identified effects of browning associated with adverse outcomes, and as more studies are being conducted, a very different picture has emerged about WAT browning and its detrimental effect in acute and chronic hypermetabolic conditions. Therefore, the notion that browning is supposedly beneficial may be inadequate. In this review we analyze how and why browning in chronic hypermetabolic associated diseases can be detrimental and lead to adverse outcomes. PMID- 27397609 TI - Associations between osteoporosis and coronary artery disease in postmenopausal women. AB - OBJECTIVE: Coronary artery disease (CAD) and osteoporosis are major causes of mortality and morbidity in postmenopausal women. We aimed to investigate the association between osteoporosis and CAD in asymptomatic postmenopausal women at a single center. METHODS: This study included 863 postmenopausal women without histories of cardiovascular diseases who visited the Health Promotion Center from June 1, 2004 to May 31, 2015. All subjects were screened for bone mineral density (BMD) by dual-energy X-ray absorptiometry and for the degree of CAD by multidetector computed tomography. RESULTS: Low BMD including osteopenia and osteoporosis was found to be significantly associated with old age, low body mass index, and a higher prevalence of diabetes mellitus. The incidences of CAD including a high coronary artery calcium score (>=100), obstructive coronary artery disease, and multivessel disease were significantly higher in subjects with low BMD. After adjusting for age and cardiovascular risk factors, osteoporosis was associated with a high coronary artery calcium score (p = 0.015) and with obstructive coronary artery disease (p = 0.002). There was a trend toward significance with multivessel disease (p = 0.052). CONCLUSIONS: High coronary artery calcium score and obstructive coronary artery disease, as revealed by multidetector computed tomography, were associated with osteoporosis in asymptomatic postmenopausal women, independent of cardiovascular risk factors and age. PMID- 27397610 TI - Clinical characteristics and long-term outcome of acute kidney injury in patients with HBV-related acute-on-chronic liver failure. AB - Acute kidney injury (AKI) is a common complication in patients with decompensated cirrhosis and is also an important cause for poor outcome. This study aimed at investigating the clinical characteristics and long-term prognosis of AKI in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). A total of 1167 patients with HBV-related ACLF from January 2010 to January 2015 were enrolled and divided into two groups, AKI group (n=308) and non AKI group (n=859). All patients were followed up to investigate clinical characteristics, long-term overall survival (OS) and risk factors. AKI occurrence was found to be 26.4% in patients with HBV-related ACLF. The patients in the AKI group and the non-AKI group had a 30-day OS of 44.8% and 70.3%, 90-day OS of 17.9% and 55.4%, and 1-year OS of 15.6% and 51.2%, respectively. Significant differences were observed in the 30-day, 90-day and 1-year OS among subgroups with different AKI stages. It was found that high WBC, neutrophil, ALT and MELD score were risk factors for 30-day mortality, whereas hepatic encephalopathy, high MELD score, mean arterial pressure and PLT were risk factors for 90-day mortality. Two criteria, the KDIGO and AKIN, showed parallel results in staging AKI in patients with HBV-related ACLF (kappa=0.807, P<.001). AKI is closely associated with increased short-term mortality in Chinese HBV-related ACLF patients, particularly in those with infection and high MELD score. Both KDIGO and AKIN criteria can be used for staging AKI in patients with HBV-related ACLF. PMID- 27397608 TI - Physical activity outcomes in afterschool programs: A group randomized controlled trial. AB - INTRODUCTION: Afterschool programs (ASPs) across the US are working towards achieving the standard of all children accumulating 30min of moderate-to-vigorous physical activity (MVPA) during program time. This study describes the two-year impact of an intervention designed to assist ASPs meeting the 30min/day MVPA standard. METHODS: Using a two-year delayed treatment, group randomized controlled trial, 20 ASPs serving ~1700 children/year (6-12yrs) were randomized to either an immediate (n=10, baseline-2013 and 2yrs intervention fall-2013-to spring-2015) or delayed group (n=10, baseline 2013-2014 and 1yr intervention fall 2014-to-spring-2015). The intervention, Strategies-To-Enhance-Practice (STEPs), focused on programming MVPA in the daily schedule, training of staff and leaders, and ongoing technical support/assistance. Accelerometry-derived proportion of children meeting the 30min/day MVPA standard was measured in the spring of each year. Mixed model logistic regressions were used to examine the change in the odds of achieving the MVPA standard. Analyses were conducted in 2015. Data were collected in one southeastern US state. RESULTS: Immediate boys (n=677) and delayed girls (n=658) increased the percent achieving 30min MVPA/day from 35.9% to 47.0% (odds ratio [OR]=1.88, 95% CI 1.18-3.00) and 13.1% to 19.1% (OR=1.42, 95% CI 1.03-1.96). Immediate girls (n=613) and delayed boys (n=687) exhibited a nonsignificant increase from 19.1% to 21.6% (OR=1.20, 95% CI 0.84-1.72) and 29.0% to 31.3% (OR=1.13, 95%CI 0.80-1.58). CONCLUSIONS: STEPs can have an impact on children's MVPA and time spent sedentary, yet was unable to fully achieve the goal of all children accumulating 30minMVPA/day. Additional efforts are need to identify strategies ASPs can use to meet this important public health standard. PMID- 27397611 TI - Changes in lipid raft proteome upon TNF-alpha stimulation of cystic fibrosis cells. AB - We have previously shown (i) that the cystic fibrosis transmembrane regulator (CFTR) locates to lipid raft-like microdomains of epithelial cells upon TNF-alpha proinflammatory stimulation; and (ii) that TNF-alpha increases the membrane localization and the channel function of F508del-mutated CFTR. In the present work, we hypothesized that CFTR mutations modify the proteome of lipid rafts in the same proinflammatory conditions. We prepared lipid rafts from HeLa cells transfected with either wild-type or F508del-CFTR and incubated for 10min with 100U/mL of TNF-alpha. Proteins were extracted, trypsin digested, and peptides analyzed by high resolution MS. Proteins were quantified by a stable isotope labeling with amino acids in cell culture approach. Out of the 22 proteins differentially recruited in lipid rafts after proinflammatory exposure, 17 were increased in F508del cells with respect to wild-type, including two G-protein coupled receptors, three anion transporters, and one cell surface mucin. In both HeLa and bronchial epithelial cells we confirmed that G-protein coupled receptor 5A relocates to lipid rafts along with F508del-CFTR after TNF-alpha treatment. These results could enlighten the cross-talk between CFTR and TNF-alpha and its impact on the cell response to proinflammatory challenge. BIOLOGICAL SIGNIFICANCE: CFTR mutations are at the origin of cystic fibrosis. The latter disease is characterized, among other symptoms, by a defective management of infection and inflammation in the airways. Short exposure to the proinflammatory cytokine TNF-alpha targets mutated CFTR to the plasma membrane and increases its chloride channel activity. The results hereby presented show a substantial modification of the lipid raft proteome in the same conditions, and may enlighten the effect of this cytokine and the role of CFTR in the cell response to inflammation. PMID- 27397613 TI - Fungal lytic polysaccharide monooxygenases bind starch and beta-cyclodextrin similarly to amylolytic hydrolases. AB - Starch-binding modules of family 20 (CBM20) are present in 60% of lytic polysaccharide monooxygenases (LPMOs) catalyzing the oxidative breakdown of starch, which highlights functional importance in LPMO activity. The substrate binding properties of starch-active LMPOs, however, are currently unexplored. Affinities and binding-thermodynamics of two recombinant fungal LPMOs toward starch and beta-cyclodextrin were shown to be similar to fungal CBM20s. Amplex Red assays showed ascorbate and Cu-dependent activity, which was inhibited in the presence of beta-cylodextrin and amylose. Phylogenetically, the clustering of CBM20s from starch-targeting LPMOs and hydrolases was in accord with taxonomy and did not correlate to appended catalytic activity. Altogether, these results demonstrate that the CBM20-binding scaffold is retained in the evolution of hydrolytic and oxidative starch-degrading activities. PMID- 27397612 TI - Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient. AB - BACKGROUND & AIMS: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing. METHODS: Tumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands. RESULTS: Although several tumor-specific neo-epitopes were predicted in silico, none could be validated by mass spectrometry. Instead, a personalized multi-peptide vaccine containing non-mutated tumor-associated epitopes was designed and applied. Immunomonitoring showed vaccine-induced T cell responses to three out of seven peptides administered. The pulmonary metastasis resected after start of vaccination showed strong immune cell infiltration and perforin positivity, in contrast to the previous lesions. The patient remains clinically healthy, without any radiologically detectable tumors since March 2013 and the vaccination is continued. CONCLUSIONS: This remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma. LAY SUMMARY: Metastatic cholangiocarcinomas, cancers that originate from the liver bile ducts, have very limited treatment options and a fatal prognosis. We describe a novel therapeutic approach in such a patient using a personalized multi-peptide vaccine. This vaccine, developed based on the characterization of the patient's tumor, evoked detectable anti-tumor immune responses, associating with long-term tumor-free survival. PMID- 27397614 TI - Response to: Mitochondrial neuropathy affects peripheral and cranial nerves and is primary or secondary or both. PMID- 27397615 TI - The Complementarity Between Protein-Specific and General Pathogenicity Predictors for Amino Acid Substitutions. AB - The usage of next-generation sequencing with biomedical/clinical purposes has fuelled the demand for tools that assess the functional impact of sequence variants. For single amino acid variants, general methods (GM), based on biophysics/evolutionary principles and trained by pooling variants from many proteins, are already available. Until now, their accuracy range (~80%) has limited their usage in clinical applications. In parallel, a series of studies indicate that protein-specific predictors (PSP), using only information from the protein of interest, could frequently surpass the performance of GM. However, two reasons suggest that this may not always be the case: the existence of a performance threshold affecting both GM and PSP, and the effect of training data scarcity. Here, we characterize the relationship between the two approaches deriving 82 PSP and comparing them with several GM (PolyPhen-2, SIFT, PON-P2, MutationTaster2, CADD). We find a complementary relationship between PSP and GM, with no approach always outperforming the other. However, the relationship varies between two limiting situations, for example, PSP are frequently outperformed by PON-P2, the best GM; however, the opposite happens when we compare PSP and SIFT. Finally, we explore how the observed complementarity could lead to increased success rates in pathogenicity prediction. PMID- 27397616 TI - Population-based study of presbyopia in Nicaragua. AB - BACKGROUND: Uncorrected presbyopia can greatly impact a person's quality of life and employment prospects. Nicaragua is the poorest country in Latin America and there are no population-based reports of prevalence of presbyopia in Nicaragua. METHODS: A cross-sectional population-based household survey was conducted. The sample was selected through random cluster sampling. Adults 35 years and older were enlisted through a door-to-door method using aged-based sampling. All enumerated household members 35 years and older were asked to attend a free visual acuity screening. Autorefraction was done and then uncorrected distance vision and near visual acuity were measured for all subjects. All those who had distance or near vision that was 6/12 or worse underwent a clinical examination, which included refraction at distance and near. Free spectacles were provided. RESULTS: Of the 3,390 subjects surveyed, 37.1 per cent reported that they wore spectacles on a regular basis. A total of 1,871 (55.2 per cent) of those enumerated were examined. The prevalence of near visual impairment (6/12 [N 6] or worse) was 79.6 per cent for the 35 to 49-year-old group, 97.3 per cent for the 50 to 64-year-old group and 96.7 per cent for the 65 and over group. Of those reporting for the examination, 82.2 per cent did not have glasses. Of those examined, 10 per cent did not need spectacles, four per cent were given spectacles for distance only, 38 per cent spectacles for distance and near, 42 per cent spectacles for near only and seven per cent were referred for medical evaluation due to ocular pathology. During the refractions, 91.5 per cent were corrected to 6/12 or better at distance and 89.4 per cent were corrected to 6/12 or better at near. CONCLUSION: The majority of the participants who were examined did not have the spectacles that they needed. Over one-third of those participants who presented without spectacles had distance vision better than 6/12 and could be improved to good near vision with ready-made near-only spectacles. PMID- 27397617 TI - Safety and Efficacy of Doxorubicin Drug-Eluting Embolic Chemoembolization of Hepatocellular Carcinoma Supplied by Extrahepatic Collateral Arteries. AB - PURPOSE: To assess safety and efficacy of doxorubicin drug-eluting embolic (DEE) transarterial chemoembolization of hepatocellular carcinoma (HCC) by extrahepatic collateral arteries. MATERIALS AND METHODS: Records of 177 patients with HCC who underwent 338 consecutive DEE chemoembolization procedures from 2011 to 2014 were retrospectively reviewed. A subgroup of 16 patients (13 men, 3 women, median age 66 y) underwent 24 procedures for 17 HCCs via extrahepatic arteries and was included in the study. Median tumor size was 3.1 cm (range, 1.0-10.3 cm). Extrahepatic collaterals included right inferior phrenic (19 procedures; 12 patients), adrenal (4 procedures; 3 patients), and cystic arteries (2 procedures; 2 patients). Radiographic response was assessed by Modified Response Evaluation Criteria in Solid Tumors criteria. Complications were defined by National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS: DEE chemoembolization achieved stable disease in 6 (35.3%), partial response in 6 (35.3%), and complete response in 4 (23.5%) HCCs. Disease progression was ultimately observed in 8 tumors (47.1%), with mean time to progression of 8.3 months after chemoembolization (range, 2-13 mo). Three minor and 5 major complications occurred in 8 patients; 2 minor complications were rash in vascular distribution after right inferior phrenic artery DEE chemoembolization. The 5 major complications were transient hepatotoxicity that resolved within 4-80 days; 1 was accompanied by pleural effusion requiring hospitalization. A mean 13.4 months after DEE chemoembolization, 67% of transplant candidates proceeded to liver transplant. CONCLUSIONS: DEE transarterial chemoembolization via extrahepatic collaterals was effective and facilitated bridging to transplant. It was generally well tolerated; transient hepatotoxicity was the most common major complication. PMID- 27397618 TI - Endovascular Management of Budd-Chiari Syndrome with Inferior Vena Cava Thrombosis: A 14-Year Single-Center Retrospective Report of 55 Patients. AB - PURPOSE: To evaluate safety and efficacy of balloon dilation and stent placement combined with thrombus aspiration and thrombolysis to treat patients with Budd Chiari syndrome (BCS) with inferior vena cava (IVC) thrombosis. MATERIALS AND METHODS: Charts from 55 consecutive patients with primary BCS and IVC thrombosis treated between April 2000 and August 2014 were retrospectively analyzed. Transcatheter aspiration and percutaneous recanalization were attempted in all patients, and stents were placed if balloon dilation was successful. Catheter directed thrombolysis was performed when evident clot burden was present after recanalization. RESULTS: Technically successful IVC recanalization was achieved in 53 of 55 patients (96.4%). Technical failures in 2 patients were due to long segment of IVC obstruction. A stent was placed in 47 of 53 patients (88.7%). Thrombus was successfully aspirated in 23 patients, and thrombolytic treatment was administered to 13 patients. Median follow-up was 58 months (range, 8-180 mo). No symptomatic pulmonary embolism occurred. Reocclusion occurred in 8 patients, and 6 of these patients (75%) underwent repeat recanalization by balloon dilation with or without stents. Cumulative 1-, 5-, and 10-year primary patency rates were 94%, 89%, and 66%. Alanine transaminase and alkaline phosphatase levels were independent risk factors for reocclusion. Cumulative 1-, 5-, and 10-year survival rates were 90%, 86%, and 86%. Child-Pugh score and reocclusion were independent predictors of survival. CONCLUSIONS: Percutaneous vena caval balloon dilation and stent placement with thrombus aspiration and thrombolytic therapy is safe and effective for treatment of patients with BCS and IVC thrombosis. PMID- 27397619 TI - Effectiveness of Embolization or Sclerotherapy of Pelvic Veins for Reducing Chronic Pelvic Pain: A Systematic Review. AB - PURPOSE: Chronic pelvic pain (CPP) in the presence of dilated and refluxing pelvic veins is often described as pelvic congestion syndrome (PCS), although the causal relationship between pelvic vein incompetence and CPP has not been established. Percutaneous embolization is the principal treatment for PCS, with high success rates cited. This study was undertaken to systematically and critically review the effectiveness of embolization of incompetent pelvic veins. MATERIALS AND METHODS: A comprehensive search strategy encompassing various terms for pelvic congestion, pelvic pain, and embolization was deployed in 17 bibliographic databases, with no restriction on study design. Methodologic quality was assessed. The quality and heterogeneity generally precluded meta analysis. Results were tabulated and described narratively. RESULTS: Twenty-one prospective case series and one poor-quality randomized trial of embolization (involving a total of 1,308 women) were identified. Early substantial relief from pain was observed in approximately 75% of women undergoing embolization, and generally increased over time and was sustained. Significant pain reductions following treatment were observed in all studies that measured pain on a visual analog scale. Repeat intervention rates were generally low. There were few data on the impact on menstruation, ovarian reserve, or fertility, but no concerns were noted. Transient pain was common following foam embolization, and there was a < 2% risk of coil migration. CONCLUSIONS: Embolization appears to provide symptomatic relief of CPP in the majority of women and is safe, although the quality of the evidence is low. PMID- 27397620 TI - Percutaneous Vertebroplasty for Palliative Treatment of Painful Osteoblastic Spinal Metastases: A Single-Center Experience. AB - PURPOSE: To evaluate safety and efficacy of fluoroscopy-guided percutaneous vertebroplasty (PVP) for painful osteoblastic spinal metastases. MATERIALS AND METHODS: PVP was performed in 39 consecutive patients (median age, 60.1 y +/- 9.5) with 51 osteoblastic metastatic spinal lesions; 14 patients had pathologic fractures. The patients were followed for 3-30 months (average, 14.5 mo +/- 7.4). Visual analog scale (VAS), Oswestry Disability Index (ODI), and Karnofsky performance scale (KPS) were used to evaluate pain, quality of life, and performance status before the procedure and at 3 days and 1, 3, 6, 12, and 18 months after the procedure. RESULTS: Technical success was achieved in all patients. Minimal follow-up time was 3 months. Mean VAS scores declined significantly from 7.4 +/- 1.1 before the procedure to 2.5 +/- 0.9 by day 3 after the procedure and were 2.1 +/- 1.1 at 1 month, 2.0 +/- 1.1 at 3 months, 1.9 +/- 1.1 at 6 months, 1.8 +/- 0.9 at 12 months, and 1.7 +/- 0.7 at 18 months after the procedure (P < .001). ODI and KPS scores also changed after the procedure, with significant differences between baseline scores and at each follow-up examination (P < .001). Extraosseous cement leakage occurred in 15 cases without causing any clinical complications. CONCLUSIONS: PVP is a safe and effective treatment for painful osteoblastic spinal metastases. It can relieve pain, reduce disability, and improve function. PMID- 27397622 TI - The rich phase behavior of the thermopolarization of water: from a reversal in the polarization, to enhancement near criticality conditions. AB - We investigate using non-equilibrium molecular dynamics simulations the polarization of water induced by thermal gradients using the accurate TIP4P/2005 water model. The full dependence of the polarization covering a wide range of thermodynamic states, from near supercritical to ambient conditions, is reported. Our results show a strong dependence of the thermo-polarization field with the thermodynamic state. The field features a strong enhancement near the critical point, which can be rationalized in terms of the large increase and ultimately the divergence of the thermal expansion of the fluid at the critical temperature. We also show that the TIP4P/2005 model features a reversal in the sign of the thermal polarization at densities ~1 g cm(-3). The latter result is consistent with the recent observation of this reversal phenomenon in SPC/E water and points the existence of this general physical phenomenon in water. PMID- 27397621 TI - The role of Ca2+ and Ca2+ channels in the gametophytic self-incompatibility of Pyrus pyrifolia. AB - In S-RNase-based self-incompatibility, S-RNase was previously thought to function as a selective RNase that inhibits pollen whose S-haplotype matches that in the pistil. In this study, we showed that S-RNase has a distinct effect on the regulation of Ca2+-permeable channel activity in the apical pollen tube in Pyrus pyrifolia. While non-self S-RNase has no effect, self S-RNase decreases the activity of Ca2+ channels and disrupts the Ca2+ gradient at the tip of the growing pollen tube during the gametophytic self-incompatibility (GSI) response. Extracellular Ca2+ influx was suppressed 5min after self S-RNase treatment, and self-pollen tube growth was reduced at 50min after self S-RNase treatment. In the self-incompatible response, the expression of Ca2+-related genes was inhibited before RNA degradation. Therefore, self S-RNase suppresses Ca2+ influx prior to arresting pollen tube growth via RNA degradation. PMID- 27397623 TI - Enhanced brainstem and cortical encoding of sound during synchronized movement. AB - Movement to a steady beat has been widely studied as a model of alignment of motor outputs on sensory inputs. However, how the encoding of sensory inputs is shaped during synchronized movements along the sensory pathway remains unknown. To investigate this, we simultaneously recorded brainstem and cortical electro encephalographic activity while participants listened to periodic amplitude modulated tones. Participants listened either without moving or while tapping in sync on every second beat. Cortical responses were identified at the envelope modulation rate (beat frequency), whereas brainstem responses were identified at the partials frequencies of the chord and at their modulation by the beat frequency (sidebands). During sensorimotor synchronization, cortical responses at beat frequency were larger than during passive listening. Importantly, brainstem responses were also enhanced, with a selective amplification of the sidebands, in particular at the lower-pitched tone of the chord, and no significant correlation with electromyographic measures at tapping frequency. These findings provide first evidence for an online gain in the cortical and subcortical encoding of sounds during synchronized movement, selective to behavior-relevant sound features. Moreover, the frequency-tagging method to isolate concurrent brainstem and cortical activities even during actual movements appears promising to reveal coordinated processes along the human auditory pathway. PMID- 27397625 TI - Reward anticipation modulates primary motor cortex excitability during task preparation. AB - Task preparation has been associated with a transient suppression of corticospinal excitability (CSE) before target onset, but it is an open question to what extent CSE suppression during task preparation is susceptible to motivational factors. Here, we examined whether CSE suppression is modulated by reward anticipation, and, if so, how this modulation develops over time. We administered a cue-target delay paradigm in which 1000ms before target onset a cue was presented indicating whether or not reward could be obtained for fast and accurate responses in a Simon task. Single-pulse transcranial magnetic stimulation was applied over left primary motor cortex (M1) during the delay period (400, 600, or 800ms after cue onset) or 200ms after target onset, and electromyography was obtained from the right first dorsal interosseous muscle. Behaviorally, the anticipation of reward improved performance (i.e. faster reaction times). Most importantly, during reward anticipation we observed a linear decrease of motor evoked potential amplitudes that was absent when no reward was anticipated. This suggests that reward anticipation modulates CSE during task preparation. PMID- 27397624 TI - A method for the dynamic correction of B0-related distortions in single-echo EPI at 7T. AB - We propose a method to calculate field maps from the phase of each EPI in an fMRI time series. These field maps can be used to correct the corresponding magnitude images for distortion caused by inhomogeneity in the static magnetic field. In contrast to conventional static distortion correction, in which one 'snapshot' field map is applied to all subsequent fMRI time points, our method also captures dynamic changes to B0 which arise due to motion and respiration. The approach is based on the assumption that the non-B0-related contribution to the phase measured by each radio-frequency coil, which is dominated by the coil sensitivity, is stable over time and can therefore be removed to yield a field map from EPI. Our solution addresses imaging with multi-channel coils at ultra high field (7T), where phase offsets vary rapidly in space, phase processing is non-trivial and distortions are comparatively large. We propose using dual-echo gradient echo reference scan for the phase offset calculation, which yields estimates with high signal-to-noise ratio. An extrapolation method is proposed which yields reliable estimates for phase offsets even where motion is large and a tailored phase unwrapping procedure for EPI is suggested which gives robust results in regions with disconnected tissue or strong signal decay. Phase offsets are shown to be stable during long measurements (40min) and for large head motions. The dynamic distortion correction proposed here is found to work accurately in the presence of large motion (up to 8.1 degrees ), whereas a conventional method based on single field map fails to correct or even introduces distortions (up to 11.2mm). Finally, we show that dynamic unwarping increases the temporal stability of EPI in the presence of motion. Our approach can be applied to any EPI measurements without the need for sequence modification. PMID- 27397626 TI - Comparison of birth weights in patients randomly assigned to fresh or frozen thawed embryo transfer. AB - OBJECTIVE: To estimate birth weight differences between patients randomized to fresh or thawed ET. DESIGN: Post hoc analysis of results from two similar randomized trials. SETTING: Private fertility center. PATIENT(S): One hundred thirty-four first-time IVF patients, ages 18-40 years at oocyte retrieval, who had live birth. INTERVENTION(S): Patients were randomly assigned to have either fresh blastocyst transfer or all bipronuclear oocytes frozen followed by thaw, extended culture, and blastocyst transfer in a subsequent cycle. Preimplantation genetic screening was not allowed. MAIN OUTCOME MEASURE(S): Mean birth weight. RESULT(S): After allowing for the contributions of multiple significant variables (gestational age at birth, the presence of a vanished twin, number of infants delivered) in multiple linear regression, the adjusted mean birth weight was 166 g (95% confidence interval, 43-290 g) lower after fresh blastocyst transfer when compared with transfer of blastocysts derived from thawed bipronuclear oocytes. CONCLUSION(S): Birth weights are lower in cycles with fresh blastocyst transfer after controlled ovarian stimulation than in transfers of frozen-thawed embryos in the absence of ovarian stimulation. This finding confirms similar results reported in many retrospective studies. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00963625 and NCT00963079. PMID- 27397627 TI - Reducing health care disparities: a call to action. PMID- 27397628 TI - Guidelines for Corticosteroid use in Treatment of DMD. AB - The guideline development subcommittee of the American Academy of Neurology has provided an update to the 2005 treatment guidelines for use of corticosteroids (CS) in Duchenne muscular dystrophy (DMD). PMID- 27397629 TI - The "RACE" national database for recurrent acute rhinosinusitis may need a relook. PMID- 27397630 TI - Impact of donor ABH-secretor status in ABO-mismatched living donor kidney transplantation. AB - BACKGROUND: The ABO blood group is a major determinant in living donor kidney transplantation since AB antigens are expressed on renal tissue. Little attention has been directed to the ABH-secretor status of the donor kidney. As renal tissue is capable of secreting soluble ABH antigens in secretors, we examined the influence of the ABH-secretor status of kidney donors on outcome in ABO mismatched living donor kidney transplantation. STUDY DESIGN AND METHODS: We retrospectively analyzed all patients who underwent ABO-mismatched kidney transplantation at the University Hospital Basel from September 2005 to October 2013. The ABH-secretor status was determined in all donors by molecular genetic analysis. RESULTS: Of all 55 patients who received transplants, we excluded all patients with donor-specific antibodies (n = 4). Forty-one donors were secretors (78%) and 11 were nonsecretors (22%). Recipients of ABH-secretor donor organs showed a significantly higher glomerular filtration rate throughout the first 6 months posttransplant, whereas no significant influence on posttransplant anti A/B titers was found. Regression analysis revealed a significant impact on humoral rejection, whereas not on vascular or interstitial rejection in protocol kidney biopsies. CONCLUSION: The donor ABH-secretor status may have an influence on early posttransplant renal function in patients undergoing ABO-mismatched living donor kidney transplantation. Further prospective studies with long-term follow-up are needed to elucidate involved pathomechanisms. PMID- 27397631 TI - An improved method for predicting interactions between virus and human proteins. AB - The interaction of virus proteins with host proteins plays a key role in viral infection and consequent pathogenesis. Many computational methods have been proposed to predict protein-protein interactions (PPIs), but most of the computational methods are intended for PPIs within a species rather than PPIs across different species such as virus-host PPIs. We developed a method that represents key features of virus and human proteins of variable length into a feature vector of fixed length. The key features include the relative frequency of amino acid triplets (RFAT), the frequency difference of amino acid triplets (FDAT) between virus and host proteins, and amino acid composition (AC). We constructed several support vector machine (SVM) models to evaluate our method and to compare our method with others on PPIs between human and two types of viruses: human papillomaviruses (HPV) and hepatitis C virus (HCV). Comparison of our method to others with same datasets of HPV-human PPIs and HCV-human PPIs showed that the performance of our method is significantly higher than others in all performance measures. Using the SVM model with gene ontology (GO) annotations of proteins, we predicted new HPV-human PPIs. We believe our approach will be useful in predicting heterogeneous PPIs. PMID- 27397632 TI - Edgewise and subgraph-level tests for brain networks. AB - Resting-state functional magnetic resonance image is a useful technique for investigating brain functional connectivity at rest. In this work, we develop flexible regression models and methods for determining differences in resting state functional connectivity as a function of age, gender, drug intervention, or neuropsychiatric disorders. We propose two complementary methods for identifying changes of edges and subgraphs. (i) For detecting changes of edges, we select the optimal model at each edge and then conduct contrast tests to identify the effects of the important variables while controlling the familywise error rate. (ii) We adopt the network-based statistics method to improve power by incorporating the graph topological structure. Both methods have wide applications for low signal-to-noise ratio data. We propose stability criteria for the choice of threshold in the network-based statistics procedure and utilize efficient massive parallel procedure to speed up the estimation and inference procedure. Results from our simulation studies show that the thresholds chosen by the proposed stability criteria outperform the Bonferroni threshold. To demonstrate applicability, we use both methods in the context of the Oxytocin and Aging Study to determine effects of age, gender, and drug treatment on resting state functional connectivity, as well as in the context of the Autism Brain Imaging Data Exchange Study to determine effects of autism spectrum disorder on functional connectivity at rest. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27397634 TI - Inorganic materials acting as heterogeneous photocatalysts and catalysts in the same reactions. AB - General considerations on the differences and similarities between heterogeneous photocatalysis and thermal catalysis are presented. Some research papers are reviewed where a reaction has been carried out in the presence of an inorganic material used both as catalyst and photocatalyst. The existing literature often compares catalytic reactions undertaken with the contemporaneous presence of radiation, showing only that photocatalytic reactions can occur under milder experimental conditions and at much lower temperatures. Nevertheless, differences in mechanistic aspects, conversions and selectivities between catalytic and photocatalytic reactions should also be highlighted. These are due to various reasons, relating to the effects of the interaction of light with the solid surface, adsorption-desorption of species involved in the (photo)reactions, and activation energy. PMID- 27397633 TI - Mesenchymal Stromal Cells Mitigate Experimental Colitis via Insulin-like Growth Factor Binding Protein 7-mediated Immunosuppression. AB - Mesenchymal stromal cells (MSCs) have shown great potential for treating inflammatory bowel disease, which is ameliorated through paracrine cross talk between MSCs and T-cells. Members of the insulin-like growth factor binding protein (IGFBP) family have important immunomodulatory functions in MSCs, but the underlying mechanisms behind these functions have not yet been clearly elucidated. In this study, we investigate whether MSC-produced IGFBP7 is involved in immune modulation using a mouse experimental colitis model. Gene expression profiling revealed that IGFBP7 was highly expressed in MSCs. Consistent with this findings, IGFBP7 knockdown in MSCs significantly decreased their immunomodulatory properties, decreasing the antiproliferative functions of MSCs against T-cells, while also having an effect on the proinflammatory cytokine production of the T cells. Furthermore, in the mouse experimental colitis model, MSC-derived IGFBP7 ameliorated the clinical and histopathological severity of induced colonic inflammation and also restored the injured gastrointestinal mucosal tissues. In conclusion, IGFBP7 contributes significantly to MSC-mediated immune modulation, as is shown by the ability of IGFBP7 knockdown in MSCs to restore proliferation and cytokine production in T-cells. These results suggest that IGFBP7 may act as a novel MSC-secreted immunomodulatory factor. PMID- 27397635 TI - Paraparetic Guillain-Barre syndrome: Nondemyelinating reversible conduction failure restricted to the lower limbs. AB - INTRODUCTION: Paraparetic Guillain-Barre syndrome (GBS) is a rare subtype of GBS characterized by leg weakness and areflexia in the absence of neurological involvement of the arms, cranial nerves, or respiratory muscles. Onset is characterized by lower back, buttock, or leg pain, followed by development of symmetric flaccid limb weakness in the absence of sensory disturbance. METHODS: We describe an elderly woman who developed postinfectious symmetric flaccid leg weakness in the absence of sensory disturbance. Serial nerve conduction studies were carried out over 5 months. RESULTS: Antecedent infection, a monophasic disease course, and the presence of cerebrospinal fluid albuminocytological dissociation suggested a diagnosis of paraparetic GBS. Serial nerve conduction studies demonstrated nondemyelinating reversible conduction failure, which was restricted to the legs. Axonal neuropathy was supported by the presence of anti GM1 IgG antibodies. CONCLUSIONS: These findings suggest that patients with paraparetic GBS have axonal neuropathy, which is restricted to the lower limbs. Muscle Nerve 55: 281-285, 2017. PMID- 27397637 TI - Corrigendum. PMID- 27397636 TI - Advancing meta-analysis beyond simple parameter estimation. PMID- 27397638 TI - Corrigendum. PMID- 27397639 TI - Cvek pulpotomy - revisited. AB - BACKGROUND/AIM: While some studies support the notion that the time elapsed from coronal fracture and treatment with Cvek pulpotomy in permanent teeth plays an important role in minimizing the possibility of pain and discomfort, microbial pulp invasion, and ensuring pulp and periodontal healing, others consider that neither time between the accident and treatment nor size of exposure is critical if the inflamed superficial pulp tissue is amputated to the level of a healthy pulp. This study compares published data in an attempt to assess whether the outcome of Cvek pulpotomies is affected by these factors. RESULTS AND CONCLUSIONS: Evidence in the literature suggests to treat a permanent tooth with a complicated crown fracture as soon as possible to diminish the possibility of pain and prevent necrosis and infection of the pulp. Delay of treatment by 9 days or less may have minimal effect on the outcome of Cvek pulpotomies. While the literature indicates that pulp exposures of 4 mm or less may have a good prognosis after a Cvek pulpotomy, the prognosis in teeth with pulp exposures of more than 4 mm has not yet been clarified. Although the literature is not conclusive regarding a difference in the outcomes of Cvek pulpotomies in teeth with open or closed apices, it appears that teeth with open apices have a better prognosis. The outcome of a Cvek pulpotomy may be compromised by a luxation injury that diminishes the tooth's blood supply and innervation. A good restoration that prevents bacterial penetration into the tooth is essential for the success of a Cvek pulpotomy. PMID- 27397640 TI - The paradox of painless periodontal disease. AB - Periodontal diseases, primarily gingivitis and periodontitis, are characterised by progressive inflammation and tissue destruction. However, they are unusual in that they are not also accompanied by the pain commonly seen in other inflammatory conditions. This suggests that interactions between periodontal bacteria and host cells create a unique environment in which the pro-algesic effects of inflammatory mediators and factors released during tissue damage are directly or indirectly inhibited. In this review, we summarise the evidence that periodontal disease is characterised by an accumulation of classically pro algesic factors from bacteria and host cells. We then discuss several mechanisms by which inflammatory sensitisation of nociceptive fibres could be prevented through inactivation or inhibition of these factors. Further studies are necessary to fully understand the molecular processes underlying the endogenous localised hypoalgesia in human periodontal disease. This knowledge might provide a rational basis to develop future therapeutic interventions, such as host modulation therapies, against a wide variety of other human pain conditions. PMID- 27397641 TI - Growth of juvenile steelhead Oncorhynchus mykiss under size-selective pressure limited by seasonal bioenergetic and environmental constraints. AB - Increased freshwater growth of juvenile steelhead Oncorhynchus mykiss improved survival to smolt and adult stages, thus prompting an examination of factors affecting growth during critical periods that influenced survival through subsequent life stages. For three tributaries with contrasting thermal regimes, a bioenergetics model was used to evaluate how feeding rate and energy density of prey influenced seasonal growth and stage-specific survival of juvenile O. mykiss. Sensitivity analysis examined target levels for feeding rate and energy density of prey during the growing season that improved survival to the smolt and adult stages in each tributary. Simulated daily growth was greatest during warmer months (1 July to 30 September), whereas substantial body mass was lost during cooler months (1 December to 31 March). Incremental increases in annual feeding rate or energy density of prey during summer broadened the temperature range at which faster growth occurred and increased the growth of the average juvenile to match those that survived to smolt and adult stages. Survival to later life stages could be improved by increasing feeding rate or energy density of the diet during summer months, when warmer water temperatures accommodated increased growth potential. Higher growth during the summer period in each tributary could improve resiliency during subsequent colder periods that lead to metabolic stress and weight loss. As growth and corresponding survival rates in fresh water are altered by shifting abiotic regimes, it will be increasingly important for fisheries managers to better understand the mechanisms affecting growth limitations in rearing habitats and what measures might maintain or improve growth conditions and survival. PMID- 27397642 TI - Metallo-pathways to Alzheimer's disease: lessons from genetic disorders of copper trafficking. AB - Copper is an essential metal ion that provides catalytic function to numerous enzymes and also regulates neurotransmission and intracellular signaling. Conversely, a deficiency or excess of copper can cause chronic disease in humans. Menkes and Wilson disease are two rare heritable disorders of copper transport that are characterized by copper deficiency and copper overload, respectively. Changes to copper status are also a common feature of several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). In the case of AD, which is characterized by brain copper depletion, changes in the distribution of copper has been linked with various aspects of the disease process; protein aggregation, defective protein degradation, oxidative stress, inflammation and mitochondrial dysfunction. Although AD is a multifactorial disease that is likely caused by a breakdown in multiple cellular pathways, copper and other metal ions such as iron and zinc play a central role in many of these cellular processes. Pioneering work by researchers who have studied relatively rare copper transport diseases has shed light on potential metal ion related disease mechanisms in other forms of neurodegeneration such as AD. PMID- 27397643 TI - Accuracy of working diagnosis by paramedics for patients presenting with dyspnoea. AB - OBJECTIVE: The present study aims to determine the agreement between paramedic and ED or hospital working diagnosis in dyspnoeic patients. METHODS: Non consecutive written patient report forms were retrospectively audited for patients suffering from dyspnoea, who were transported to a tertiary hospital ED by ambulance paramedics. Accuracy of the paramedic working diagnosis was assessed by comparing agreement with either the primary or secondary ED diagnoses or hospital discharge diagnosis. RESULTS: The study cohort was 293 patients. Exact agreement between paramedic versus ED or hospital diagnosis was 64%, 95% CI 58 69, k = 0.58, 95% CI 0.52-0.64. Only 226 (77%) had a 'clearly documented' paramedic diagnosis. Among these, agreement with either ED or hospital diagnosis was 79%, and there was a trend towards more agreement as paramedic level of practice increased (74%, 78% and 87% for Basic, Intermediate and ALS paramedics, respectively, P = 0.07). Conversely, ALS paramedics were less likely to document a working diagnosis (30/98, 31%) compared with Intermediate (22/102, 23%) and BLS paramedics (15/93, 16%), P = 0.008. Diagnostic agreement varied according to medical condition, from anaphylaxis (100%) and asthma (86%) to acute pulmonary oedema (46%). CONCLUSIONS: There was moderate agreement between paramedic and ED or hospital diagnosis. The number of cases with no clearly documented working diagnosis suggested that a singular working diagnosis may not always serve the complexity of presentation of some dyspnoea patients: more open descriptors such as 'mixed disease' or 'atypical features' should be encouraged. PMID- 27397644 TI - Ab Initio Investigation of Cation Proton Affinity and Proton Transfer Energy for Energetic Ionic Liquids. AB - Protonation of the anion in an ionic liquid plays a key role in the hypergolic reaction between ionic liquids and oxidizers such as white fuming nitric acid. To investigate the influence of the cation on the protonation reaction, the deprotonation energy of a set of cations has been calculated at the MP2 level of theory. Specifically, guanidinium, dimethyltriazanium, triethylamine, N-ethyl-N methyl-pyrrolidinium, N-ethyl-pyridinium, 1,4-dimethyl-1,2,4-triazolium, 1-ethyl 4-methyl-1,2,4-triazolium, and 1-butyl-4-methyl-1,2,4-triazolium were studied. In addition, the net proton transfer energies from the cations to a set of previously studied anions was calculated, demonstrating an inverse correlation between the net proton transfer energy and the likelihood that the cation/anion combination will react hypergolically with white fuming nitric acid. It is suggested that this correlation occurs due to a balance between the energy released by the proton transfer and the rate of proton transfer as determined by the ionicity of the ionic liquid. PMID- 27397645 TI - Feasibility and pharmacokinetics of caudal blockade in children and adolescents with 30-50 kg of body weight. AB - BACKGROUND: Caudal blockade, although an important technique of pediatric regional anesthesia, is rarely used in children heavier than 30 kg. This reservation is due to anatomical concerns and lack of pharmacokinetic data. We therefore set out to evaluate, in pediatric patients weighing 30-50 kg, the feasibility of ultrasound-guided caudal blockade and the pharmacokinetics of caudally administered ropivacaine. METHODS: Twenty consecutive children were included. General anesthesia was used to ensure a secured airway. For the caudal punctures, we applied the same clinical standards as in smaller children, administering ropivacaine 3.1 mg.ml-1 for a volume of 1 ml.kg-1 via ultrasound guidance. Pharmacokinetic analysis was based on total plasma ropivacaine levels and included maximum concentration (Cmax ), time to Cmax (tmax ), terminal elimination half-life, area under the concentration-time curve for the 4-h sampling period, apparent total body clearance, and apparent volume of distribution. RESULTS: In all 19 cases of successful puncture, we identified the relevant anatomical structures (sacral cornua, sacral hiatus, dura mater) and verified correct administration of the local anesthetic by visualizing its cranial spread. Surgical blockade was successful in 18 of 20 cases (90%; one puncture was technically not possible and one child received intraoperatively 50 MUg fentanyl). The pharmacokinetic profile of the administered ropivacaine 3.1 mg.ml-1 indicated plasma levels within safe ranges in pediatric patients weighing 30-50 kg. CONCLUSIONS: Based on our pharmacodynamic and pharmacokinetic results, we suggest that the body weight of 50 kg it is feasible to perform effective and safe caudal blockade in children up to 50 kg body weight. PMID- 27397647 TI - Copper-catalyzed retro-aldol reaction of beta-hydroxy ketones or nitriles with aldehydes: chemo- and stereoselective access to (E)-enones and (E) acrylonitriles. AB - A copper-catalyzed transfer aldol type reaction of beta-hydroxy ketones or nitriles with aldehydes is reported, which enables chemo- and stereoselective access to (E)-alpha,beta-unsaturated ketones and (E)-acrylonitriles. A key step of the in situ copper(i)-promoted retro-aldol reaction of beta-hydroxy ketones or nitriles is proposed to generate a reactive Cu(i) enolate or cyanomethyl intermediate, which undergoes ensuing aldol condensation with aldehydes to deliver the products. This reaction uses 1.2 mol% Cu(IPr)Cl (IPr denotes 1,3 bis(2,6-diisopropylphenyl)imidazol-2-ylidene) as the catalyst in the presence of 6.0 mol% NaOtBu cocatalyst at room temperature or 70 degrees C. A range of aryl and heteroaryl aldehydes as well as acrylaldehydes are compatible with many useful functional groups being tolerated. Under the mild and weakly basic conditions, competitive Cannizzaro-type reaction of benzaldehydes and side reactions of base-sensitive functional groups can be effectively suppressed, which show synthetic advantages of this reaction compared to classic aldol reactions. The synthetic potential of this reaction is further demonstrated by the one-step synthesis of biologically active quinolines and 1,8-naphthyridine in excellent yields (up to 91%). Finally, a full catalytic cycle for this reaction has been constructed using DFT computational studies in the context of a retro aldol/aldol two-stage mechanism. A rather flat reaction energy profile is found indicating that both stages are kinetically facile, which is consistent with the mild reaction conditions. PMID- 27397646 TI - Mycotoxins, pesticides and toxic metals in commercial spices and herbs. AB - A total of 300 samples representing six condiments (black pepper, basil, oregano, nutmeg, paprika, and thyme) were analysed for 11 mycotoxins, 134 pesticides and 4 heavy metals by ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry and inductively coupled plasma mass spectrometry. Mycotoxins were detected in 4%, 10% and 30% of all nutmeg, basil and thyme samples, respectively. The residues of 24 pesticides were detected in 59% of the analysed condiments. The maximum residue levels of pesticides were exceeded in 10% of oregano and 46% of thyme samples. A risk assessment of heavy metals was performed, indicating daily intake levels far below the tolerable intake levels. PMID- 27397648 TI - Allele-specific PCR for detecting the deafness-associated mitochondrial 12S rRNA mutations. AB - Mutations in mitochondrial 12S rRNA (MT-RNR1) are the important causes of sensorineural hearing loss. Of these mutations, the homoplasmic m.1555A>G or m.1494C>T mutation in the highly conserved A-site of MT-RNR1 gene has been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. Since the m.1555A>G and m.1494C>T mutations are sensitive to ototoxic drugs, therefore, screening for the presence of these mutations is important for early diagnosis and prevention of deafness. For this purpose, we recently developed a novel allele-specific PCR (AS-PCR) which is able to simultaneously detect these mutations. To assess its accuracy, in this study, we employed this method to screen the frequency of m.1555A>G and m.1494C>T mutations in 200 deafness patients and 120 healthy subjects. Consequently, four m.1555A>G and four m.1494C>T mutations were identified; among these, only one patient with the m.1494C>T mutation had an obvious family history of hearing loss. Strikingly, clinical evaluation showed that this family exhibited a high penetrance of hearing loss. In particular, the penetrances of hearing loss were 80% with the aminoglycoside included and 20% when excluded. PCR-Sanger sequencing of the mitochondrial genomes confirmed the presence of the m.1494C>T mutation and identified a set of polymorphisms belonging to mitochondrial haplogroup A. However, the lack of functional variants in mitochondrial and nuclear modified genes (GJB2 and TRMU) in this family indicated that mitochondrial haplogroup and nuclear genes may not play important roles in the phenotypic expression of the m.1494C>T mutation. Thus, other modification factors, such as environmental factor, aminoglycosides or epigenetic modification may have contributed to the high penetrance of hearing loss in this family. Taken together, our data showed that this assay is an effective approach that could be used for detection the deafness-associated MT-RNR1 mutations. PMID- 27397649 TI - Target genes of Dpp/BMP signaling pathway revealed by transcriptome profiling in the early D.melanogaster embryo. AB - In the early Drosophila melanogaster embryo, the gene regulatory network controlled by Dpp signaling is involved in the subdivision of dorsal ectoderm into the presumptive dorsal epidermis and amnioserosa. In this work, we aimed to identify new Dpp downstream targets involved in dorsal ectoderm patterning. We used oligonucleotide D. melanogaster microarrays to identify the set of genes that are differential expressed between wild type embryos and embryos that overexpress Dpp (nos-Gal4>UAS-dpp) during early stages of embryo development. By using this approach, we identified 358 genes whose relative abundance significantly increased in response to Dpp overexpression. Among them, we found the entire set of known Dpp target genes that function in dorsal ectoderm patterning (zen, doc, hnt, pnr, ush, tup, and others) in addition to several up regulated genes of unknown functions. Spatial expression pattern of up-regulated genes in response to Dpp overexpression as well as their opposing transcriptional responses to Dpp loss- and gain-of-function indicated that they are new candidate target genes of Dpp signaling pathway. We further analyse one of the candidate genes, CG13653, which is expressed at the dorsal-most cells of the embryo during a restricted period of time. CG13653 orthologs were not detected in basal lineages of Dipterans, which unlike D. melanogaster develop two extra-embryonic membranes, amnion and serosa. We characterized the enhancer region of CG13653 and revealed that CG13653 is directly regulated by Dpp signaling pathway. PMID- 27397650 TI - Downregulation of Peptidylprolyl isomerase A promotes cell death and enhances doxorubicin-induced apoptosis in hepatocellular carcinoma. AB - Peptidylprolyl isomerase A (PPIA) is a peptidyl-prolyl cis-trans isomerase that is known to play a critical role in the development of many human cancers. However, the precise biological function of PPIA in hepatocellular carcinoma (HCC) remains largely unclear. In this study, lentiviral overexpression vectors and small interfering RNA knockdown methods were employed to investigate the biological effects of PPIA in HCC. PPIA levels in HCC tissues and peritumoral tissues were detected by real-time Polymerase Chain Reaction (RT-PCR), Western blotting, and immunohistochemistry. Our results indicate that PPIA levels were significantly higher in the HCC tissues compared to the matched peritumoral tissues. Moreover, PPIA expression was significantly associated with tumor size in these tissues. Interestingly, serum PPIA (sPPIA) levels were significantly higher in healthy controls compared to the HCC patients. Knockdown or overexpression of PPIA was shown to downregulate and upregulate cell growth, respectively. Moreover, PPIA siRNA knockdown appears to promote doxorubicin induced apoptosis in HCC cells, altering the expression of downstream apoptotic factors. In summary, our results indicate that PPIA may play a pivotal role in HCC by regulating cell growth and could serve as a novel marker and therapeutic molecular target for HCC patients. PMID- 27397651 TI - Attitudes towards lung cancer screening in socioeconomically deprived and heavy smoking communities: informing screening communication. AB - BACKGROUND: While discussion continues over the future implementation of lung cancer screening, low participation from higher risk groups could limit the effectiveness of any national screening programme. OBJECTIVES: To compare smokers' beliefs about lung cancer screening with those of former and never smokers within a low socioeconomic status (SES) sample, to explore the views of lower SES smokers and ex-smokers in-depth, and to provide insights into effective engagement strategies. DESIGN, SETTING AND PARTICIPANTS: Using proactive, community-based recruitment methods, we surveyed 175 individuals from socioeconomically deprived communities with high smoking prevalence and subsequently interviewed 21 smokers and ex-smokers. Participants were approached in community settings or responded to a mail-out from their housing association. RESULTS: Interviewees were supportive of screening in principle, but many were doubtful about its ability to deliver long-term survival benefit for their generation of "heavy smokers." Lung cancer was perceived as an uncontrollable disease, and the survey data showed that fatalism, worry and perceived risk of lung cancer were particularly high among smokers compared with non-smokers. Perceived blame and stigma around lung cancer as a self-inflicted smokers' disease were implicated by interviewees as important social deterrents of screening participation. The belief that lungs are not a treatable organ appeared to be a common lay explanation for poor survival and undermined the potential value of screening. CONCLUSIONS: Attitudes towards screening among this high-risk group are complex. Invitation strategies need to be carefully devised to achieve equitable participation in screening. PMID- 27397652 TI - Ensemble Perception, Summary Statistics, and Perceptual Awareness: A Response. PMID- 27397653 TI - Aged complement factor H knockout mice kept in a clean barriered environment have reduced retinal pathology. AB - Age-related macular degeneration (AMD) is the largest cause of visual loss in those over 60 years in the West and is a condition increasing in prevalence. Many diseases result from genetic/environmental interactions and 50% of AMD cases have an association with polymorphisms of the complement system including complement factor H. Here we explore interactions between genetic predisposition and environmental conditions in triggering retinal pathology in two groups of aged complement factor H knock out (Cfh(-/-)) mice. Mice were maintained over 9 months in either a conventional open environment or a barriered pathogen free environment. Open environment Cfh(-/-) mice had significant increases in subretinal macrophage numbers, inflammatory and stress responses and reduced photoreceptor numbers over mice kept in a pathogen free environment. Hence, environmental factors can drive retinal disease in these mice when linked to complement deficits impairing immune function. Both groups of mice had similar levels of retinal amyloid beta accumulation. Consequently there is no direct link between this and inflammation in Cfh(-/-) mice. PMID- 27397654 TI - A selective fluorescent probe for the detection of Cd(2+) in different buffer solutions and water. AB - A simple fluorescent probe NHQ based on quinoline was successfully prepared via one-step synthesis. The probe NHQ exhibited "turn-on" fluorescence and excellent selectivity toward Cd(2+) in different buffer solutions such as Tris-HCl buffer solution, HEPES buffer solution, and PBS buffer solution, and even in water. Moreover, the binding model of NHQ with Cd(2+) was definitely confirmed by the single crystal X-ray diffraction studies of the complex. PMID- 27397655 TI - Criminal Law and Parasomnias: Some Legal Clarifications. PMID- 27397656 TI - Quality Assessment of Systematic Reviews on the Efficacy of Oral Appliance Therapy for Adult and Pediatric Sleep-Disordered Breathing. AB - STUDY OBJECTIVES: To assess the methodological quality of published systematic reviews (SRs) and meta-analyses (MAs) about the efficacy of oral appliances (OA) in the management of adult and pediatric sleep-disordered breathing (SDB). METHODS: SRs/MAs that evaluated the efficacy of OA therapy on the treatment of SDB in human subjects of all age groups were sought. Multiple electronic databases were searched for articles published in any language from the database's inception until January 2016. Two reviewers independently selected and then assessed the methodological quality of the studies using the Assessment of Multiple Systematic Reviews (AMSTAR) measurement tool. RESULTS: Thirteen reviews on adult SDB were included (2 SRs and 11 SRs with MAs). Of those, seven were medium quality and six were high quality. Only four reviews were included on pediatric SDB (3 SRs and 1 SR with MA). Three of these were of high quality and one was medium quality. The identified limitations in the included reviews were failing to reference the excluded studies or describe reasons for exclusion, lack of applying valid criteria to assess the quality of included studies, lack of publication bias assessment, and absence of conflicts of interest reporting. CONCLUSIONS: Overall, SRs/MAs on OA therapy for adult and pediatric SDB were conducted with acceptable methodological quality. High AMSTAR scores should not be extrapolated as a proxy of the methodological quality of the included evidence. There is a need for more primary studies and then that information can be used to be synthesized through SRs on pediatric SDB. PMID- 27397657 TI - Apical Lung Herniation Associated with Continuous Positive Airway Pressure in a 4 Year-Old Girl. AB - ABSTRACT: We report a case of apical lung herniation through the superior thoracic aperture of an obese child using nocturnal CPAP. Lung herniation has been described in association with congenital thoracic abnormalities and elevated intra-thoracic pressure, such as trauma. This patient was hospitalized with community acquired pneumonia and required nocturnal CPAP for treatment of concurrent obstructive sleep apnea. Her lung hernia was discovered incidentally on routine follow-up chest radiography and resolved with cessation of CPAP treatment. Lung herniation in association with the use of continuous positive airway pressure (CPAP) has not been previously described. PMID- 27397658 TI - Alternatives to Clonazepam in REM Behavior Disorder Treatment. PMID- 27397659 TI - Quality Measure for Screening for Adult Obstructive Sleep Apnea by Primary Care Physicians. AB - ABSTRACT: Obstructive sleep apnea (OSA) is a highly prevalent condition which remains under-diagnosed and under-treated. Untreated OSA is associated with several chronic medical conditions, a reduction in quality of life and increases in health care costs. Therefore, early identification of undiagnosed cases is important. Implementation of a screening measure in a primary care environment for populations at high-risk for OSA could improve patient outcomes and reduce the health care burden of untreated OSA. PMID- 27397660 TI - And the Doctor Continues: "...But I Have to Choose My Gear Wisely". PMID- 27397661 TI - Effectiveness of Oral Appliances in Obstructive Sleep Apnea with Respiratory Arousals. AB - STUDY OBJECTIVES: To compare adherence and treatment effects with an oral appliance (OA) in patients with different types of obstructive sleep apnea (OSA): those with mainly respiratory arousals ("arousers"), and those with oxygen desaturations ("desaturaters") at polysomnography (PSG). METHODS: A prospective intervention study on 72 "tired snorers" with "normal" home sleep study (HSS), but later diagnosed as OSA with PSG, who accepted OA treatment. They were offered evaluation with a follow-up PSG and questionnaires, including the Epworth Sleepiness Scale (ESS), general health (GH), satisfaction, and side effects. RESULTS: Sixty-six patients, 33 arousers and 33 desaturaters, were adapted to OA. The 1-year adherence rate was significantly higher among arousers (85%) than desaturaters (55%) (p = 0.034). Thirty-six of 66 patients underwent follow-up PSG; the apnea-hypopnea index was significantly reduced in 22 arousers from a median of 14 to 3 (p < 0.001), and in 14 desaturaters from 18 to 7 (p = 0.002; no significant group difference). ESS and GH showed no significant improvements in either group, although sleepy "arousers" (ESS >= 10) significantly improved their ESS. In total, 77% reported side effects, while 63% were still satisfied with the OA treatment. Gender analysis showed a significant dominance of females classified as "arousers" (p = 0.025). CONCLUSIONS: OSA patients with mainly arousals at PSG showed higher adherence to OA treatment, compared to patients with desaturations. Both groups responded similarly to treatment: improved nocturnal respiration, but only a small reduction of symptoms. We suggest that "tired snorers" with "normal HSS" should be offered PSG, and if OSA, also OA treatment. PMID- 27397662 TI - Relationship of Fluid Accumulation in the Neck to Sleep Structure in Men during Daytime Sleep. AB - STUDY OBJECTIVES: Induction of fluid overload during sleep in older men causes fluid accumulation in the neck, worsens obstructive sleep apnea (OSA), and reduces sleep efficiency and slow wave sleep. However, it is not clear whether disrupted sleep structure was related to age, fluid accumulation, or to OSA severity as assessed by the apnea-hypopnea index (AHI). We hypothesize that fluid accumulation in the neck is a significant contributor to the sleep structure. METHODS: Twenty non-obese men, 46 +/- 11 years, underwent a daytime sleep study following a night of sleep deprivation. Before and after sleep, neck circumference (NC), upper airway cross-sectional area, and neck fluid volume (NFV) were assessed. Stepwise regression analyses were used to determine factors that contributed to sleep structure, AHI, and arousal frequency. Independent factors were age, NC, DeltaNC, DeltaNFV, and AHI (excluded for AHI and arousal). RESULTS: Subjects slept for 145 +/- 44 minutes with a mean AHI of 26 +/- 25. After sleep, NC and NFV increased and the upper airway narrowed (all: p < 0.001). DeltaNC and DeltaNFV correlated directly with %N2 and inversely with %N3 sleep. Regression analyses revealed that only DeltaNC correlated directly with %N2 sleep (r2 = 0.44, p = 0.001). DeltaNC, DeltaNFV, and pre-sleep NC correlated inversely with %N3 sleep (r2 = 0.76, p < 0.001). Pre-sleep NC and DeltaNC correlated directly with AHI and arousal frequency. CONCLUSIONS: Fluid accumulation in the neck and larger neck circumference are related to impaired sleep structure with reduced %N3 sleep. Fluid accumulation in the neck had stronger contribution to sleep structure than AHI or age. PMID- 27397663 TI - Effect of Antihypertensive Medications on the Severity of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension (HTN). Increasing evidence from animal and human studies suggests that HTN exacerbates OSA. We performed a systematic review and meta-analysis of studies evaluating the effect of anti-hypertensive medications on the severity of OSA. METHODS: A literature search of PubMed and Embase was done using search concepts of OSA, HTN, and drug classes used to treat HTN. Studies that reported changes in the severity of OSA objectively by using apnea-hypopnea index (AHI) or respiratory disturbance index (RDI) were included. Pooled mean difference estimates were calculated. Tests for heterogeneity, publication bias, and subgroup sensitivity analysis were conducted. RESULTS: Of 27,376 studies screened, only 11 met inclusion criteria, including 5 randomized controlled trials and 6 single-arm prospective trials. The pooled mean difference estimate (95% confidence interval [CI]), based on a random-effects model, was -5.69 (95% CI -10.74 to -0.65), consistent with an overall decrease in AHI or RDI attributable to antihypertensive medications. The effect size was even more pronounced, -14.52 (95% CI -25.65 to -3.39), when only studies using diuretics were analyzed. There was no significant heterogeneity or publication bias among the studies. Meta-regression indicated neither age, baseline AHI, nor change in systolic/diastolic blood pressure influenced the results. CONCLUSIONS: Collectively, findings from these relatively small, short-term studies tend to support the contention that treatment with antihypertensive agents confers a statistically significant, albeit small, reduction in the severity of OSA, which may be more pronounced with the use of diuretics. PMID- 27397664 TI - Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials. AB - STUDY OBJECTIVES: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials. METHODS: Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18-64 years) and elderly (>= 65 years) patients with insomnia. Patients were randomized to suvorexant 20/15 mg (non-elderly/elderly), suvorexant 40/30 mg (non elderly/elderly), or placebo; by design, fewer patients were randomized to 20/15 mg. Efficacy was assessed by self-reported and polysomnography (PSG; subset of patients) sleep maintenance and onset endpoints. RESULTS: Suvorexant 20/15 mg (N = 493 treated) was effective compared to placebo (N = 767 treated) on patient reported and PSG sleep maintenance and onset endpoints at Night-1 (PSG endpoints) / Week-1 (subjective endpoints), Month-1 and Month-3, except for effects on PSG sleep onset at Month-3. Suvorexant 20/15 mg was generally well tolerated, with 3% of patients discontinuing due to adverse events over 3 months vs. 5.2% on placebo. Somnolence was the most common adverse event (6.7% vs. 3.3% for placebo). There was no systematic evidence of rebound or withdrawal signs or symptoms when suvorexant was discontinued after 3 months of nightly use. CONCLUSIONS: Suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629. PMID- 27397665 TI - Sleep Apnea in Hurler Syndrome: Looking Beyond the Upper Airway. AB - ABSTRACT: This case involves a 13-month-old male with Hurler syndrome. Due to oxygen desaturations during sleep, this patient was referred for polysomnography, which revealed severe mixed sleep apnea (apnea-hypopnea index [AHI] 72 events/h). Because sleep apnea in patients with Hurler syndrome is frequently attributed to upper airway obstruction, he was referred to otolaryngology. Prior to his evaluation by otolaryngology, he underwent ventriculoperitoneal (VP) shunt placement, which had been scheduled due to hydrocephalus on brain magnetic resonance imaging (MRI). After VP shunt placement, his oxygen desaturations during sleep resolved. Repeat polysomnogram revealed mild sleep apnea (AHI 1.9). The etiology of his sleep apnea was likely his hydrocephalus. This is the first report of a patient with Hurler syndrome with sleep apnea which markedly improved with ventriculostomy and VP shunt placement. This highlights the importance of considering neurological etiologies for sleep apnea in Hurler's patients, despite their predisposition for airway obstruction. PMID- 27397666 TI - Management of Snoring and Sleep Apnea in Australian Primary Care: The BEACH Study (2000-2014). AB - STUDY OBJECTIVES: To characterize the changes in management of snoring and obstructive sleep apnea (OSA) in general practice in Australia. METHODS: The Bettering the Evaluation And Care of Health (BEACH) study is a nationally representative rolling cross-sectional survey of general practice activity in Australia. We analyzed all adult (age 18+ y) encounters for OSA or snoring, annually from 2000 to 2014 (approximately 1,000 general practitioners (GPs) per year recording approximately 100,000 patient encounters per year). RESULTS: The management rate of OSA rose from 94 to 296 per 100,000 encounters, whereas management rate of snoring remained steady at approximately 15 to 25 per 100,000 encounters. The majority of patients managed for OSA were: middle-aged (25-64 y; 71.3% of all patients); overweight (90%); male (62%), although there was a trend for an increase in the proportion being female over the study period (21 to 37 per 100 encounters). Referral rates were high for both OSA (59 per 100 problems managed) and snoring (69 per 100), although medical referrals (to a sleep clinic or respiratory physician) were significantly higher for patients managed for OSA than for snoring (90% vs. 60% of all referrals). Surgical referrals were higher for snoring than for OSA (37% vs. 3% of all referrals). CONCLUSIONS: The management rate for OSA tripled from 2000 to 2014, while the rate for snoring remained steady. GPs significantly relied on the advice of other health professionals to manage OSA; however, their referral patterns aligned with what most specialists would recommend. COMMENTARY: A commentary on this article appears in this issue on page 1081. PMID- 27397667 TI - A rare cause of elevated alpha fetoprotein in patient with cirrhosis. PMID- 27397668 TI - Does the infusion rate of fluid affect rapidity of mean arterial pressure restoration during controlled hemorrhage. AB - OBJECTIVE: This study aimed to compare 2 fluid infusion rates of lactated Ringer (LR) and hydroxyethyl starch (HES) 130/0.4 on hemodynamic restoration at the early phase of controlled hemorrhagic shock. METHODS: Fifty-six anesthetized and ventilated piglets were bled until mean arterial pressure (MAP) reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes. After this period, 4 resuscitation groups were studied (n=14 for each group): HES infused at 1 or 4mL/kg per minute or LR1 infused at 1 or 4mL/kg per minute until baseline MAP was restored. Hemodynamic assessment using PiCCO monitoring and biological data were collected. RESULTS: Time to restore baseline MAP +/-10% was significantly lower in LR4 group (11+/-11 minutes) compared to LR1 group (41+/-25 minutes) (P=.0004). Time to restore baseline MAP +/-10% was significantly lower in HES4 group (4+/-3 minutes) compared to HES1 (11+/-4 minutes) (P=.0003). Time to restore baseline MAP +/-10% was significantly lower with HES vs LR whatever the infusion rate. No statistically significant difference was observed in cardiac output, central venous saturation, extravascular lung water, and arterial lactate between 4 and 1 mL/kg per minute groups. CONCLUSIONS: In this controlled hemorrhagic shock model, a faster infusion rate (4 vs 1mL/kg per minute) significantly decreased the time for restoring baseline MAP, regardless of the type of infused fluid. The time for MAP restoration was significantly shorter for HES as compared to LR whatever the fluid infusion rate. PMID- 27397669 TI - A comparison of direct laryngoscopic views in different head and neck positions in edentulous patients. AB - OBJECTIVE: Proper head and neck positioning is an important factor for successful direct laryngoscopy, and the optimum position in edentulous patients is unclear. We compared direct laryngoscopic views in simple head extension, sniffing, and elevated sniffing positions in edentulous patients. METHODS: Eighteen adult edentulous patients scheduled for elective surgery were included in the study. After induction of anesthesia, the laryngeal view was assessed under direct laryngoscopy using the percentage of glottic opening (POGO) score in 3 different head and neck positions in a randomized order: simple head extension without a pillow, sniffing position with a pillow of 7 cm, and elevated sniffing position with a pillow of 10 cm. After assessment of the laryngeal views, tracheal intubation was performed. RESULTS: A significant difference was observed in the laryngeal views assessed at the 3 head positions (P= .001). The POGO scores (mean [SD]) in the sniffing position (78.9% [19.7%]) and elevated sniffing position (72.6% [20.8%]) were significantly improved compared to that with simple head extension (53.8% [25.9%]) (P= .001, respectively). The sniffing position provided the best laryngeal view. The mean POGO scores were higher in the sniffing position than the elevated sniffing position, but no significant difference was observed between these 2 positions (P= .268). CONCLUSIONS: The sniffing and elevated sniffing positions provide better laryngeal views during direct laryngoscopy compared to simple head extension in edentulous patients. PMID- 27397670 TI - Quantification of in vivo site-specific Asp isomerization and Asn deamidation of mAbs in animal serum using IP-LC-MS. AB - BACKGROUND: Isomerization of aspartic acid and deamidation of asparagine are two common amino acid modifications that are of particular concern if located within the complementarity-determining region of therapeutic antibodies. Questions arise as to the extent of modification occurring in circulation due to potential exposure of the therapeutic antibody to different pH regimes. RESULTS: To enable evaluation of site-specific isomerization and deamidation of human mAbs in vivo, immunoprecipitation (IP) has been combined with LC-MS providing selective enrichment, separation and detection of naive and modified forms of tryptic peptides comprising complementarity-determining region sequences. CONCLUSION: IP LC-MS can be applied to simultaneously quantify in vivo drug concentrations and measure the extent of isomerization or deamidation in PK studies conducted during the drug discovery stage. PMID- 27397671 TI - Pseudocirrhosis and liver failure in patients with metastatic breast cancer after treatment with palbociclib. PMID- 27397674 TI - In Memoriam Marie-Louise Druart. PMID- 27397672 TI - Monitoring G protein-coupled receptor and beta-arrestin trafficking in live cells using enhanced bystander BRET. AB - Endocytosis and intracellular trafficking of receptors are pivotal to maintain physiological functions and drug action; however, robust quantitative approaches are lacking to study such processes in live cells. Here we present new bioluminescence resonance energy transfer (BRET) sensors to quantitatively monitor G protein-coupled receptors (GPCRs) and beta-arrestin trafficking. These sensors are based on bystander BRET and use the naturally interacting chromophores luciferase (RLuc) and green fluorescent protein (rGFP) from Renilla. The versatility and robustness of this approach are exemplified by anchoring rGFP at the plasma membrane or in endosomes to generate high dynamic spectrometric BRET signals on ligand-promoted recruitment or sequestration of RLuc-tagged proteins to, or from, specific cell compartments, as well as sensitive subcellular BRET imaging for protein translocation visualization. These sensors are scalable to high-throughput formats and allow quantitative pharmacological studies of GPCR trafficking in real time, in live cells, revealing ligand dependent biased trafficking of receptor/beta-arrestin complexes. PMID- 27397673 TI - Hemolytic Disease of the Fetus and Newborn: Modern Practice and Future Investigations. AB - Red blood cell (RBC) sensitization occurs in some women in response to exposure to paternally derived RBC antigens during pregnancy or to nonself antigens on transfused RBCs during their lifetime. Once sensitized, future pregnancies may be at risk for hemolytic disease of the fetus and newborn. Although great strides have been made over the past few decades in terms of identifying blood group antigens and in predicting fetal anemia through the use of noninvasive monitoring, many questions remain in terms of understanding RBC alloimmunization risk factors, preventative therapies, and treatment strategies. At the present time, there is room for improvement in these areas in both developed and developing countries. Evidence-based, universal guidelines describing recommended RBC antigen matching transfusion strategies for girls or women, before pregnancy or during intrauterine transfusions, would be welcomed. A better understanding of the mechanism(s) of action of Rh immunoglobulin, first introduced more than half of a century ago and one of the most successful immunoprophylaxis therapies in existence today, would also be a large step forward. For example, answers to questions of the role(s) that fetal RBC clearance, antigen masking, antigen modulation, and immune suppression play in the effectiveness of Rh immunoglobulin may help to guide the development of novel preventative therapies during pregnancy for immunization to RhD and non-RhD antigens. Furthermore, a better understanding of the importance of anti-RhD or other alloantibody glycosylation patterns may be beneficial not only in developing such novel immunoprophylaxis therapies but also in predicting the clinical significance of existing maternal alloantibodies. One other area of need includes the development of therapies beyond intrauterine transfusions to mitigate the dangers of maternal alloantibodies to developing fetuses. We challenge physicians, scientists, and funding agencies to prioritize studies of RBC alloimmunization and hemolytic disease of the fetus and newborn and to invest in the children of our future. PMID- 27397675 TI - In Memoriam Professor Dr. Hendrik Lacroix. PMID- 27397676 TI - Formation Chirurgicale: Passe, Present et Avenir. PMID- 27397677 TI - Opleiding Heelkunde in Belgie Verleden, Heden en Toekomst. PMID- 27397678 TI - Glucose Fluctuations are Not Modulated by the Proportion of Calories from Macronutrients or Spontaneous Total Energy Expenditure in Adults with Cystic Fibrosis. AB - OBJECTIVES: To determine the modifiable factors affecting glucose variability in people with cystic fibrosis (CF). CF-related diabetes (CFRD) is the most common complication of CF, and its presence increases morbidity and mortality in patients. Patients with CF (with and without CFRD) have potentially harmful glucose fluctuations and glucose excursions when compared to healthy adults. Carbohydrate intake and exercise have been shown to affect glycemia. Therefore, our hypothesis was that the proportion of energy from carbohydrates and total energy expenditure (TEE) would influence glucose fluctuations in adults with CF. METHODS: A cross-sectional study involved 36 patients with CF, in whom continuous glucose monitoring systems were installed. Glucose fluctuations were then quantified using 3 indexes: mean amplitude of glucose excursions, standard deviation and coefficient of variation. Patients filled out a 3-day food diary to quantify energy intake and the proportions of calories from carbohydrates, fats and proteins, and they wore Sensewear Armbands to estimate spontaneous TEE and footsteps walked. Glucose tolerance status was determined using oral glucose tolerance tests. RESULTS: Patients with CF with normal and impaired glucose tolerance had fewer glucose fluctuations than patients with CFRD (p<0.05). However, linear regression models used to determine whether nutrition or energy expenditure affects glucose fluctuations demonstrated that energy, the proportion of carbohydrates, of fat and of protein, TEE or the number of footsteps walked did not affect glucose fluctuation indexes (p>0.05). CONCLUSIONS: TEE and the proportion of energy from carbohydrates did not affect glucose fluctuations in adults with CF. PMID- 27397679 TI - The relationship between hepatic steatosis and skeletal muscle mass index in men with type 2 diabetes. AB - Recent cross-sectional studies revealed that sarcopenia is associated with non alcoholic fatty liver disease (NAFLD) in general population. However, it remains to be elucidated that the association between skeletal muscle mass index (SMI) and hepatic steatosis in patients with type 2 diabetes. In this cross-sectional study of 145 Japanese patients (79 men and 66 women) with type 2 diabetes, we examined the correlation of SMI with hepatic steatosis. Skeletal muscle mass was estimated from bioimpedance analysis measurements and SMI (%) was defined as skeletal muscle mass (kg)/total body weight (kg) * 100. Controlled attenuation parameter (CAP) evaluated with transient elastography, was used for assessment of hepatic steatosis. In addition, we also investigated the association between SMI and prevalence of NAFLD, which was defined as CAP over 237.8 dm-1, using logistic regression analysis. Fifty-eight (74%) men and thirty-nine (60%) women had NAFLD. Multiple regression analysis demonstrated that SMI was independently correlated with CAP (beta = -0.35, P = 0.007) in men after adjusting for age, body mass index, hemoglobin A1c, triglycerides/ HDL-C ratio, C-reactive protein and gamma glutamyl transferase. On the other hand, SMI was not associated with CAP in women. Odds ratio per incremental 1% of SMI for prevalence of NAFLD was 0.80 (95% CI 0.64-0.97, P = 0.021) after adjusting for age, BMI, smoking statues, triglycerides/ HDL-C ratio, HbA1c, and gamma-glutamyl transferase in men. In conclusion, SMI was negatively associated with hepatic steatosis in men with type 2 diabetes. PMID- 27397680 TI - Augmented expression of gamma-glutamyl transferase 5 (GGT5) impairs testicular steroidogenesis by deregulating local oxidative stress. AB - An increasingly pro-oxidant environment has been widely implicated in causing dysfunction of testicular steroidogenesis, but little progress has been made in understanding the underlying molecular mechanism. Here, we report that gamma glutamyl transferase 5 (GGT5), a key metabolism component responsible for the catalysis of important anti-oxidant glutathione (GSH), is predominantly expressed in mammalian Leydig cells (LCs). Deregulated GGT5 expression negatively correlates with testosterone deficiency in the testes of type 2 diabetic mice. Consistently, overexpression of GGT5 potentiates the susceptibility of TM3 LCs to spontaneous oxidative stress during luteinizing hormone (LH)-stimulated steroidogenesis. From a mechanistic standpoint, the deleterious effect of GGT5 overexpression on testicular steroidogenesis may stem from an alteration of the local redox state because of GSH deficiency. The above-mentioned response might involve the impairment of extracellular signal-related kinase activation mediated directly by oxidative injury or indirectly by abnormal P38 activation, which in turn inhibits steroidogenic acute regulatory protein abundance in mitochondria and thus significantly sabotages the rate-limiting step during LH-induced steroidogenesis. Alternatively, GGT5 overexpression induces heme oxygenase 1 (HO 1) expression, which, as a key catalyst responsible for the oxidative degradation of heme, may inhibit the activities of the cytochrome P450 monooxygenases, thus substantially impairing testicular steroidogenesis. These results, coupled with the differential roles of mitogen-activated protein kinases and HO-1 signaling in spermatogenesis, lead us to propose a model in which a delicate balance between these two pathways modulated by the GGT5/oxidative stress cascade plays a central role during LH-stimulated steroidogenesis. PMID- 27397681 TI - The ability of prehabilitation to influence postoperative outcome after intra abdominal operation: A systematic review and meta-analysis. AB - BACKGROUND: Preoperative physical fitness is predictive of postoperative outcome. Patients with lesser aerobic capacity are at greater risk of postoperative complications, longer hospital stays, and mortality. Prehabilitation may improve physical fitness, but it is unknown whether enhanced fitness translates to an improvement in postoperative outcome. METHODS: This systematic review and meta analysis aimed to assess the ability of prehabilitation to influence postoperative outcome after intra-abdominal operations. Randomized controlled trials with at least 1 group undergoing a preoperative exercise intervention/prehabilitation were included. The following databases were searched: AMED, CINAHL, EMBASE, PubMed/Medline, and The Cochrane Library. Data extracted from 9 full-articles included author(s), population demographics, type of operation, postoperative measures of outcome, and type of treatment of the prehabilitation and control groups. Methodologic quality was assessed using GRADEpro, and the Cochrane risk of bias tool was used to measure study bias. RESULTS: Prehabilitation consisting of inspiratory muscle training, aerobic exercise, and/or resistance training can decrease all types of postoperative complications after intra-abdominal operations (odds ratio: 0.59, 95% confidence interval: 0.38-0.91, P = .03). It is unclear from our meta-analysis whether prehabilitation can decrease postoperative length of stay, because the number of studies that examined length of stay was small (n = 4). No postoperative mortality was reported in any study, and conclusions could not be drawn on the ability of exercise to influence operative mortality. The methodologic quality of studies was, however, "very low." CONCLUSION: Prehabilitation appears to be beneficial in decreasing the incidence of postoperative complications; however, more high-quality studies are needed to validate its use in the preoperative setting. PMID- 27397682 TI - Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra. AB - We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. PMID- 27397683 TI - Release of SR Proteins from CLK1 by SRPK1: A Symbiotic Kinase System for Phosphorylation Control of Pre-mRNA Splicing. AB - Phosphorylation has been generally thought to activate the SR family of splicing factors for efficient splice-site recognition, but this idea is incompatible with an early observation that overexpression of an SR protein kinase, such as the CDC2-like kinase 1 (CLK1), weakens splice-site selection. Here, we report that CLK1 binds SR proteins but lacks the mechanism to release phosphorylated SR proteins, thus functionally inactivating the splicing factors. Interestingly, CLK1 overcomes this dilemma through a symbiotic relationship with the serine arginine protein kinase 1 (SRPK1). We show that SRPK1 interacts with an RS-like domain in the N terminus of CLK1 to facilitate the release of phosphorylated SR proteins, which then promotes efficient splice-site recognition and subsequent spliceosome assembly. These findings reveal an unprecedented signaling mechanism by which two protein kinases fulfill separate catalytic features that are normally encoded in single kinases to institute phosphorylation control of pre mRNA splicing in the nucleus. PMID- 27397684 TI - Temporal and Spatial Uncoupling of DNA Double Strand Break Repair Pathways within Mammalian Heterochromatin. AB - Repetitive DNA is packaged into heterochromatin to maintain its integrity. We use CRISPR/Cas9 to induce DSBs in different mammalian heterochromatin structures. We demonstrate that in pericentric heterochromatin, DSBs are positionally stable in G1 and recruit NHEJ factors. In S/G2, DSBs are resected and relocate to the periphery of heterochromatin, where they are retained by RAD51. This is independent of chromatin relaxation but requires end resection and RAD51 exclusion from the core. DSBs that fail to relocate are engaged by NHEJ or SSA proteins. We propose that the spatial disconnection between end resection and RAD51 binding prevents the activation of mutagenic pathways and illegitimate recombination. Interestingly, in centromeric heterochromatin, DSBs recruit both NHEJ and HR proteins throughout the cell cycle. Our results highlight striking differences in the recruitment of DNA repair factors between pericentric and centromeric heterochromatin and suggest a model in which the commitment to specific DNA repair pathways regulates DSB position. PMID- 27397685 TI - Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase. AB - Replisome assembly at eukaryotic replication forks connects the DNA helicase to DNA polymerases and many other factors. The helicase binds the leading-strand polymerase directly, but is connected to the Pol alpha lagging-strand polymerase by the trimeric adaptor Ctf4. Here, we identify new Ctf4 partners in addition to Pol alpha and helicase, all of which contain a "Ctf4-interacting-peptide" or CIP box. Crystallographic analysis classifies CIP-boxes into two related groups that target different sites on Ctf4. Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats. Our data reveal unexpected complexity of Ctf4 function, as a hub that connects multiple accessory factors to the replisome. Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation. PMID- 27397686 TI - Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome. AB - DNA replication during S phase is accompanied by establishment of sister chromatid cohesion to ensure faithful chromosome segregation. The Eco1 acetyltransferase, helped by factors including Ctf4 and Chl1, concomitantly acetylates the chromosomal cohesin complex to stabilize its cohesive links. Here we show that Ctf4 recruits the Chl1 helicase to the replisome via a conserved interaction motif that Chl1 shares with GINS and polymerase alpha. We visualize recruitment by EM analysis of a reconstituted Chl1-Ctf4-GINS assembly. The Chl1 helicase facilitates replication fork progression under conditions of nucleotide depletion, partly independently of Ctf4 interaction. Conversely, Ctf4 interaction, but not helicase activity, is required for Chl1's role in sister chromatid cohesion. A physical interaction between Chl1 and the cohesin complex during S phase suggests that Chl1 contacts cohesin to facilitate its acetylation. Our results reveal how Ctf4 forms a replisomal interaction hub that coordinates replication fork progression and sister chromatid cohesion establishment. PMID- 27397687 TI - Distinct Functions of Argonaute Slicer in siRNA Maturation and Heterochromatin Formation. AB - Small-RNA (sRNA)-guided transcriptional gene silencing by Argonaute (Ago) containing complexes is fundamental to genome integrity and epigenetic inheritance. The RNA cleavage ("Slicer") activity of Argonaute has been implicated in both sRNA maturation and target RNA cleavage. Typically, Argonaute slices and releases the passenger strand of duplex sRNA to generate active silencing complexes, but it remains unclear whether slicing of target nascent RNAs, or other RNAi components, also contributes to downstream transcriptional silencing. Here, we develop a strategy for loading the fission yeast Ago1 with a single-stranded sRNA guide, which bypasses the requirement for slicer activity in generation of active silencing complexes. We show that slicer-defective Ago1 can mediate secondary sRNA generation, H3K9 methylation, and silencing similar to or better than wild-type and associates with chromatin more efficiently. The results define an ancient and minimal sRNA-mediated chromatin silencing mechanism, which resembles the germline-specific sRNA-dependent transcriptional silencing pathways in Drosophila and mammals. PMID- 27397689 TI - Acne Knowledge of Hispanic Parents of Teenagers with Mild to Moderate Acne. AB - We performed a cross-sectional study of Hispanic and non-Hispanic parents of children with acne using a survey designed to determine their level of awareness of acne and its treatment; 82% of Hispanic parents and 40% of non-Hispanic parents agreed that a health care provider should treat mild acne (p < 0.001). Hispanic parents of adolescents with acne agreed more frequently than non Hispanic parents that children with mild and moderate acne should be taken to a health care provider for treatment, but they tended not to visit health care providers. Future studies should aim to determine the reasons for this discrepancy, after which culturally sensitive educational programs can be developed to address this disparity. PMID- 27397688 TI - Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER Mitochondrial Interface. AB - The ER-mitochondrial interface is central to calcium signaling, organellar dynamics, and lipid biosynthesis. The ER and mitochondrial membranes also host sources and targets of reactive oxygen species (ROS), but their local dynamics and relevance remained elusive since measurement and perturbation of ROS at the organellar interface has proven difficult. Employing drug-inducible synthetic ER mitochondrial linkers, we overcame this problem and demonstrate that the ER mitochondrial interface hosts a nanodomain of H2O2, which is induced by cytoplasmic [Ca(2+)] spikes and exerts a positive feedback on calcium oscillations. H2O2 nanodomains originate from the mitochondrial cristae, which are compressed upon calcium signal propagation to the mitochondria, likely due to Ca(2+)-induced K(+) and concomitant water influx to the matrix. Thus, ER mitochondrial H2O2 nanodomains represent a component of inter-organelle communication, regulating calcium signaling and mitochondrial activities. PMID- 27397690 TI - The ability of orthodontists and oral/maxillofacial surgeons to predict eruption of lower third molar. AB - BACKGROUND: The aim of this study was to evaluate the ability of oral/maxillofacial surgeons (OMFSs) and orthodontists to predict third molar eruption by examining a simple panoramic radiograph in cases where full spontaneous eruption occurred. METHODS: Panoramic radiographs of 17 patients, 13 16 years of age, were obtained just after orthodontic treatment (T1), when the third molars were intraosseous. The radiographs at T1 were presented to 28 OMFSs and 28 orthodontists-who were asked to give a prognosis for the lower third molars on both sides (n = 34). The full spontaneous eruption of all third molars was clinically observed when patients were older than 18 years (T2). These teeth were clinically asymptomatic at T1 and T2. RESULTS: OMFSs decided by extractions in 49.6 % of cases while orthodontists in 37.8 % (p < 0.001), when the radiographs were examined at T1. Agreement between OMFSs and orthodontists was excellent (Kappa = 0.76, p < 0.0001), as well as intragroup agreement for both OMFSs (Kappa = 0.83) and orthodontists (Kappa = 0.96). CONCLUSIONS: Despite a remarkable agreement for third molar prognosis, orthodontists and OMFSs were unable to predict lower third molar eruption by examining a simple panoramic radiograph. Both indicated extractions of a considerable number of spontaneously erupted asymptomatic teeth. PMID- 27397691 TI - Development of a local relative value unit to measure radiologists' computed tomography reporting workload. AB - INTRODUCTION: Demand for CT examinations is continually increasing, with radiologists' reporting times (RRTs) being the major constraint in CT productivity. As CT complexity varies according to the anatomical region, there is a need for methods that normalize radiologist work to address reporting workload. METHODS: All CT orders, from July 2013 to February 2015, from a 850-bed tertiary-care, university-based general hospital in southern Brazil, were studied. Type of examination and RRTs were retrieved from our Radiology Information System/IMPAX. Based on RRTs, after exclusion of spurious results, we calculated local relative value units (L-RVUs) for different examinations. We also compared these results with the US-Medicare/Medicaid RVU (US-RVU). RESULTS: The query resulted in 42,382 occurrences for 24 tests. Among the tests, 15 had sample size n >= 100. The 9 tests with n < 100 were grouped into 4 sets of tests, resulting in the analysis of 17 categories of tests. RRTs for total abdomen CT, thorax CT and central nervous system CT were 17.1 +/- 14.6, 14.2 +/- 11.1 and 7.0 +/- 6.5 minutes, respectively. L-RVUs for the 17 categories of tests were calculated, resulting in values from 1.00 to 4.18. L-RVU and US-RVU displayed no correlation (r = 0.05; P-value = 0.86). CONCLUSION: Computed tomography radiologists' reporting workload varies considerably across different tests. Moreover, the lack of significant correlation between US-RVU and L-RVU highlights the need for contextualized methods to locally address radiologists' reporting workload. Thus, the use of L-RVU could aid in planning and managing a CT Unit. PMID- 27397693 TI - Basement membrane fragments in the context of the epithelial-to-mesenchymal transition. AB - The epithelial-to-mesenchymal transition (EMT) enables cells of epithelial phenotype to become motile and change to a migratory mesenchymal phenotype. EMT is known to be a fundamental requisite for tissue morphogenesis, and EMT-related pathways have been described in cancer metastasis and tissue fibrosis. Epithelial structures are marked by the presence of a sheet-like extracellular matrix, the basement membrane, which is assembled from two major proteins, laminin and collagen type IV. This specialized matrix is essential for tissue function and integrity, and provides an important barrier to the potential pathogenic migration of cells. The profound phenotypic transition in EMT involves the epithelial cells disrupting the basement membrane. Matrix metalloproteinases (MMPs) are known to cleave components of basement membranes, but MMP-basement membrane crosstalk during EMT in vivo is poorly understood. However, MMPs have been reported to play a role in EMT-related processes and a variety of basement membrane fragments have been shown to be released by specific MMPs in vitro and in vivo exhibiting distinct biological activities. This review discusses general considerations regarding the basement membrane in the context of EMT, a possible role for specific MMPs in EMT and highlights biologically active basement membrane fragments liberated by MMPs. PMID- 27397694 TI - Quality of Posttreatment Care Among Breast Cancer Survivors in the University of California Athena Breast Health Network (Athena). AB - INTRODUCTION: Multiple oncology providers are involved in the initial breast cancer treatment. To better understand the patterns and quality of posttreatment breast cancer care, we surveyed patients who had been treated at each of the 5 University of California (UC) cancer centers. PATIENTS AND METHODS: We identified breast cancer patients diagnosed in 2008-2009 from hospital tumor registries; invitations for the mailed survey on posttreatment care were sent between September 2011 and November 2012. The survey requested information on the number and type of provider visits, discussion of key topics, use of treatment summaries, and survivorship care plans (SCP). RESULTS: A total of 329 patients completed the survey. The mean age of respondents was 60.5 years, and they were 3.2 years since diagnosis (range, 1.6-4.8 years). A total of 82% had continued posttreatment care at a UC facility, and they reported high numbers of clinical follow-up visits, with an average of > 2 providers (range, 1-5). Surgery-only patients reported an average of 4 to 5 office visits a year; patients who received surgery, radiation, and chemotherapy reported 5 to 6 office visits a year. Overall, 45% of women reported receiving a treatment summary; receipt of a SCP was reported by 59%, occurring significantly more often among those in follow up at a UC (P = .004). CONCLUSION: Patients reported visits to multiple providers during their follow-up care, in excess of what is recommended by current guidelines. This was in spite of many women reporting that they had received a SCP. PMID- 27397695 TI - In vitro oral drug permeation models: the importance of taking physiological and physico-chemical factors into consideration. AB - INTRODUCTION: The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico chemical factors that may have an influence on these techniques are critically reviewed. The shortcomings identified for some of the in vitro techniques are discussed in conjunction with novel ways to improve and thereby overcome some challenges. Expert opinion: Although conventional in vitro methods and theories are used as basic guidelines to predict drug absorption, critical evaluations have identified some shortcomings. Advancements in technology have made it possible to investigate and understand the role of physiological and physico chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment. PMID- 27397692 TI - Causes and consequences of nuclear envelope alterations in tumour progression. AB - Morphological changes in the size and shape of the nucleus are highly prevalent in cancer, but the underlying molecular mechanisms and the functional relevance remain poorly understood. Nuclear envelope proteins, which can modulate nuclear shape and organization, have emerged as key components in a variety of signalling pathways long implicated in tumourigenesis and metastasis. The expression of nuclear envelope proteins is altered in many cancers, and changes in levels of nuclear envelope proteins lamins A and C are associated with poor prognosis in multiple human cancers. In this review we highlight the role of the nuclear envelope in different processes important for tumour initiation and cancer progression, with a focus on lamins A and C. Lamin A/C controls many cellular processes with key roles in cancer, including cell invasion, stemness, genomic stability, signal transduction, transcriptional regulation, and resistance to mechanical stress. In addition, we discuss potential mechanisms mediating the changes in lamin levels observed in many cancers. A better understanding of cause and-effect relationships between lamin expression and tumour progression could reveal important mechanisms for coordinated regulation of oncogenic processes, and indicate therapeutic vulnerabilities that could be exploited for improved patient outcome. PMID- 27397696 TI - From tRNA to miRNA: RNA-folding contributes to correct entry into noncoding RNA pathways. AB - Although RNA are synthesized as single-stranded molecules, most of them are characterized by extensive secondary structures. Two RNA that require distinct folding for biogenesis and function are miRNA and tRNA. While miRNA are processed from hairpin-containing precursors, tRNA are folded into characteristic L-shaped structures. In addition, tRNA and their precursors are a rich source of RNA fragments. Recent findings suggest that their production might be determined by structural characteristics of the tRNA substrates. Importantly, correct folding of pre-tRNA is assisted by the Lupus autoantigen La, an RNA chaperone. In this context, La interacts with pre-tRNA to prevent alternative foldings leading to mis-channeling into the miRNA pathway. Thus, RNA chaperones also function as gatekeepers for correct RNA pathway selection. PMID- 27397697 TI - Biological evaluation of new [(18) F]F-labeled synthetic amino acid derivatives as oncologic radiotracers. AB - The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)-2-amino-3-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4 ([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2 amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1 yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor-bearing model mice were acquired over 2 h after AMC administration. [(18) F]FDOPA PET studies were performed with and without S carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine-serine-cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 +/- 0.05, 1.89 +/- 0.27, and 1.74 +/- 0.13 for AMC-101, AMC-102, and AMC-103, respectively. Although the tumor uptake values of AMCs were lower than that of [(18) F]FDOPA with S-carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [(18) F]FDOPA with S-carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers. PMID- 27397698 TI - Evidence for Resident Memory T cells in Rasmussen Encephalitis. AB - Investigators from University of California Los Angeles studied the presence of different T cell subset population in the brain tissue of 7 patients with Rasmussen encephalitis, a rare neuroinflammatory disorder characterized by intractable seizures and usually associated with progressive hemi cerebral atrophy, who underwent brain surgery and compared them to patients with focal cortical dysplasia. PMID- 27397700 TI - Osteocyte lacunar properties and cortical microstructure in human iliac crest as a function of age and sex. AB - Osteocytes are suggested to play a central role in bone remodeling. Evaluation of iliac crest biopsies is a standard procedure for evaluating bone conditions in the clinical setting. Despite the widespread use of such biopsies, little is known about the population of osteocytes in the iliac crest from normal individuals. Contradicting results have been reported on osteocyte lacunar properties in human bone. Hence, a solid understanding of the osteocyte population in healthy bone and the effect of age and sex is needed as good reference data are lacking. Furthermore, the role of cortical bone in bone quality has recently been suggested to be more important than previously realized. Therefore, the present study assesses osteocyte lacunar properties and cortical microstructure of the iliac crest as a function of age and sex. A total of 88 iliac crest bone samples from healthy individuals (46 women, aged 18.5 96.4years and 42 men, aged 22.6-94.6years) with an even age-distribution were examined using synchrotron radiation MUCT and in house MUCT, with >5*10(6) osteocyte lacunae measured and analyzed. The study revealed that osteocyte lacunar volumes were unaffected by both age and sex. Osteocyte lacunar density did not differ between women and men, and only showed a significant decrease with age when pooling data from both sexes. Cortical porosity and Haversian canal density increased while cortical thickness decreased with age, with cortical thinning dominating the age-related cortical bone loss. None of the cortical microstructural parameters showed any sex dependency. Only weak links between osteocyte lacunar properties and cortical microstructural properties in iliac crest bone were found. Interestingly, the Haversian canal diameters were significantly but weakly negatively correlated with osteocyte lacunar volumes. PMID- 27397699 TI - Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density. AB - Aiming to identify genomic variants associated with osteoporosis, we performed a genome-wide association meta-analysis of bone mineral density (BMD) at Ward's triangle of the hip in 7175 subjects from 6 samples. We performed in silico replications with femoral neck, trochanter, and inter-trochanter BMDs in 6912 subjects from the Framingham heart study (FHS), and with forearm, femoral neck and lumbar spine BMDs in 32965 subjects from the GEFOS summary results. Combining the evidence from all samples, we identified 2 novel loci for areal BMD: 1q43 (rs1414660, discovery p=1.20*10(-8), FHS p=0.05 for trochanter BMD; rs9287237, discovery p=3.55*10(-7), FHS p=9.20*10(-3) for trochanter BMD, GEFOS p=0.02 for forearm BMD, nearest gene FMN2) and 2q32.2 (rs56346965, discovery p=7.48*10(-7), FHS p=0.10 for inter-trochanter BMD, GEFOS p=0.02 for spine BMD, nearest gene NAB1). The two lead SNPs rs1414660 and rs56346965 are eQTL sites for the genes GREM2 and NAB1 respectively. Functional annotation of GREM2 and NAB1 illustrated their involvement in BMP signaling pathway and in bone development. We also replicated three previously reported loci: 5q14.3 (rs10037512, discovery p=3.09*10(-6), FHS p=8.50*10(-3), GEFOS p=1.23*10(-24) for femoral neck BMD, nearest gene MEF2C), 6q25.1 (rs3020340, discovery p=1.64*10(-6), GEFOS p=1.69*10( 3) for SPN-BMD, nearest gene ESR1) and 7q21.3 (rs13310130, discovery p=8.79*10( 7), GEFOS p=2.61*10(-7) for spine BMD, nearest gene SHFM1). Our findings provide additional insights that further enhance our understanding of bone development, osteoporosis, and fracture pathogenesis. PMID- 27397701 TI - Visualizing unbiased and biased unweighted meta-analyses. PMID- 27397702 TI - Complications in gastrointestinal endoscopy. PMID- 27397703 TI - Endoscopic classification for colorectal tumors using narrow-band imaging. PMID- 27397704 TI - WEO Newsletter. PMID- 27397705 TI - Erratum. PMID- 27397706 TI - Coming in Postgraduate Medicine. PMID- 27397710 TI - What's Happening in Medicine! PMID- 27397708 TI - Problems/Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27397711 TI - Washington Report on Health. PMID- 27397712 TI - Meetings and Courses. PMID- 27397714 TI - Your Investments. PMID- 27397715 TI - The Medical Muse. PMID- 27397717 TI - Cannabis consumption patterns among frequent consumers in Uruguay. AB - BACKGROUND: In 2013, Uruguay became the first country to fully regulate the cannabis market, which now operates under state control. Cannabis can be legally acquired in three ways: growing it for personal use (self-cultivation), cannabis club membership, and from pharmacies (not yet implemented). Users must be entered into a confidential official registry to gain access. METHODS: This article presents findings of a Respondent Driven Sample survey of 294 high-frequency cannabis consumers in the Montevideo metropolitan area. RESULTS: Frequent consumers resort to more than one method for acquiring cannabis, with illegal means still predominating after 1 year of the new regulation law. Cannabis users overwhelmingly support the current regulation, but many of them are reluctant to register. CONCLUSIONS: Some of the attitudes and behaviors of the high-frequency consumers pose a challenge to the success of the cannabis law. Individuals relying on more than one method of access defy the single access clause, a prerequisite for legal use, while the maximum amount of cannabis individuals can access monthly seems too high even for most frequent consumers, which might promote the emergence of a grey market. Reluctance to register among a significant proportion of high-frequency consumers raises doubts about the law's ability to achieve its stated objectives. PMID- 27397718 TI - Amino Acid-Based Zwitterionic Polymer Surfaces Highly Resist Long-Term Bacterial Adhesion. AB - The surfaces or coatings that can effectively suppress bacterial adhesion in the long term are of critical importance for biomedical applications. Herein, a group of amino acid-based zwitterionic polymers (pAAZ) were investigated for their long term resistance to bacterial adhesion. The polymers were derived from natural amino acids including serine, ornithine, lysine, aspartic acid, and glutamic acid. The pAAZ brushes were grafted on gold via the surface-initiated photoiniferter-mediated polymerization (SI-PIMP). Results show that the pAAZ coatings highly suppressed adsorption from the undiluted human serum and plasma. Long-term bacterial adhesion on these surfaces was investigated, using two kinds of representative bacteria [Gram-positive Staphylococcus epidermidis and Gram negative Pseudomonas aeruginosa] as the model species. Results demonstrate that the pAAZ surfaces were highly resistant to bacterial adhesion after culturing for 1, 5, 9, or even 14 days, representing at least 95% reduction at all time points compared to the control unmodified surfaces. The bacterial accumulation on the pAAZ surfaces after 9 or 14 days was even lower than on the surfaces grafted with poly[poly(ethyl glycol) methyl ether methacrylate] (pPEGMA), one of the most common antifouling materials known to date. The pAAZ brushes also exhibited excellent structural stability in phosphate-buffered saline after incubation for 4 weeks. The bacterial resistance and stability of pAAZ polymers suggest they have good potential to be used for those applications where long-term suppression to bacterial attachment is desired. PMID- 27397719 TI - Chitosan-based nano-in-microparticle carriers for enhanced oral delivery and anticancer activity of propolis. AB - This study reports a promising approach to enhance the oral delivery of propolis, improve its aqueous solubility and bioavailability, and allow its controlled release as well as enhancing its anticancer activity. Propolis was standardized then its solubility was improved via formulation into optimized solid dispersion (SD) matrices, and its release was controlled through incorporation into nanoparticles (NPs) of optimized composition followed by further inclusion into chitosan (Cs) microparticles. The anticancer activity of the newly developed propolis-loaded nano-in-microparticles (NIMs) was evaluated against human liver cancer (HepG2) and human colorectal cancer (HCT 116) cells. The prepared SDs, NPs and NIMs were characterized using SEM, TEM, DLS, FTIR, DSC and UV-vis spectrophotometry. The therapeutic efficiency of formulated propolis was bio assessed via cytotoxicity measurements, mitochondrial dysfunction, apoptosis induced cell death and cell cycle arrest. The results demonstrated a considerable enhancement in propolis solubility with a controlled release profile in different GIT environments. In-vitro cytotoxicity studies showed that the propolis-loaded NIMs induce more cytotoxic effect on HepG2 cells than HCT-116 cells and mediated three-fold higher therapeutic efficiency than free propolis. The apoptosis assay indicated that the propolis-loaded NIMs induce apoptosis of HepG2 cells and significantly decrease their number in the proliferative G0/G1, S and G2/M phases. PMID- 27397720 TI - Characterization and antioxidant activities of polysaccharides from the leaves of Lilium lancifolium Thunb. AB - In this study, LLP-1, LLP-2, and LLP-3 three novel polysaccharide fractions were purified from the leaves of Lilium lancifolium, and their physicochemical characterizations and antioxidant properties were investigated by chemical methods, high performance gel permeation chromatography (HPGPC), high performance liquid chromatography (HPLC), fourier transform infrared spectrometry (FT-IR), scanning electron microscopy (SEM), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay and ferrous ion chelating assay, respectively. Results showed that LLP-1, LLP-2, and LLP-3 had low protein and uronic acid contents, meanwhile, their weight-average molecular weight were estimated to be 2.25*106, 2.02*106, and 2.08*106Da, respectively. Mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose glucose and galactose were the major monosaccaherides components presenting in the polysaccharide fractions. Three polysaccharide fractions were not observed triple-helical conformation, while possessed variant surface structure. In addition, three polysaccharide fractions all exhibited significantly scavenging activities against free radical and chelate Fe2+in vitro. PMID- 27397721 TI - Severity of hypertension predicts the generalized neurocognitive deficit in schizophrenia. AB - Individuals with schizophrenia have been found to display neurocognitive deficits on the order of 1 standard deviation below the mean of healthy controls on a range of cognitive domains, with no clear pattern of deficits that characterizes the majority of individuals with schizophrenia. Such findings have led some to suggest that schizophrenia is characterized by a "generalized" neurocognitive deficit, implying that a common underlying etiology impacts all cognitive domains. Central nervous system accounts of the generalized deficit have been proposed (e.g., NMDA and GABA interneuron receptor dysfunction); however, there may also be more diffuse "general systems" abnormalities that affect brain function. The current study evaluated the role of one type of general systems abnormality, metabolic dysfunction, on global cognitive functioning in a sample of outpatients with schizophrenia (n=27) and demographically matched healthy controls (n=33). Participants completed a battery of neuropsychological tests, as well as metabolic measurements to assess blood glucose, blood pressure, and abdominal obesity. Results indicated that higher pulse pressure predicted the generalized neurocognitive deficit in schizophrenia, but not healthy controls; however, blood glucose and abdominal obesity did not predict cognitive performance in either group. These findings provide support for the role of metabolic abnormalities in the generalized neurocognitive deficit in schizophrenia, and suggest that treatment of hypertension may be a novel adjunctive treatment target for remediating cognitive deficits in schizophrenia. PMID- 27397722 TI - Evaluation of vestibular evoked myogenic potentials (VEMP) and electrocochleography for the diagnosis of Meniere's disease. AB - INTRODUCTION: Meniere's disease (MD) is an inner ear disorder characterized by episodic vertigo, tinnitus, ear fullness, and fluctuating hearing. Its diagnosis can be especially difficult in cases where vestibular symptoms are present in isolation (vestibular MD). The definitive diagnosis is made histologically and can only be performed post-mortem, after analysis of the temporal bone. Endolymphatic hydrops is a histopathological finding of the disease and occurs more often in the cochlea and saccule, followed by the utricle and semicircular canals. Vestibular evoked myogenic potentials (VEMP) emerged as the method of assessment of vestibular function in 1994. Until then, there was no unique way of assessing saccular function and the inferior vestibular nerve. Given that the saccule is responsible for most cases of severe hydrops, VEMP appears as a new tool to assist in the diagnosis of MD. OBJECTIVE: To evaluate the sensitivity and specificity of VEMP and electrocochleography (EcochG) in the diagnosis of definite MD compared with clinical diagnosis. METHODS: The study includes 12 patients (24 ears) diagnosed with definite MD defined according to the clinical criteria proposed by the American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) in 1995, as well as 12 healthy volunteers allocated to the control group (24 ears). A clinical diagnosis by the AAO-HNS criteria was considered as the gold standard. All patients underwent an otoneurological examination, including pure tone and speech audiometry, VEMP, and extratympanic EcochG. The sensitivity and specificity to detect the presence or absence of disease were calculated, as well as their 95% confidence intervals. The reliability of VEMP and EcochG in both ears was assessed using the kappa index. RESULTS: In both tests and in both ears, the ability to diagnose healthy cases was high, with specificity ranging from 84.6% to 100%. Moreover, the ability of the tests to diagnose the disease varied from low to moderate sensitivity, with values ranging from 37.5% to 63.6%. The agreement of both tests in the right ear, measured by the kappa coefficient, was equal to 0.54 (95% CI: 0.20-0.89), indicating a moderate agreement. In the left ear, that agreement was equal to 0.07 (95% CI: -0.33 to 0.46), indicating a weak correlation between the tests. The sensitivity of the VEMP for the right ear was 63.6% and for the left ear, 62.5%. The sensitivity of EcochG for the right ear was 63.6% and 37.5% for the left ear. CONCLUSION: The specificity of both tests was high, and the sensitivity of VEMP was higher than that of EcochG. PMID- 27397723 TI - Somatic gene mutation analysis of triple negative breast cancers. AB - OBJECTIVES: The aims of this study were to analyze triple negative breast cancer (TNBC) using an expanded next generation sequencing (NGS) assay, assess the clinical relevance using a recently described database, and correlate tumor morphology with detected genetic alterations. METHODS: DNA was isolated from twenty primary TNBCs and genes of interest were enriched and sequenced with hybrid capture, followed by variant detection and functional and clinical annotation. The JAX-CTPTM assay detects actionable variants in the form of single nucleotide variations, small insertions and deletions (<=50 bp), and copy number variants in 358 genes in specimens containing a neoplastic cell content of >=50%. The JAX-CKB is a comprehensive database that curates tumor phenotype, genetic variant and protein effect, therapeutic relevance, and available treatment options. RESULTS: 18/20 (90%) of TNBCs contained at least one somatic mutation detected by the JAX-CTPTM. MYC amplification was the most common alteration, present in 75% of tumors. TP53, AURKA, and KDR mutations were each present in 30% (6/20) of cases. Related recruiting clinical trials, extracted from JAX-CKB, included 166 for breast cancer, of which 17 were specific to only the TNBC subtype. All 17 trials were testing at least one therapy that targets a mutation identified in this sample set. The majority (89%) of tumors with basal-like histologic features had MYC amplification. CONCLUSIONS: The expanded gene panel identified a variety of clinically actionable gene alterations in TNBCs. The identification of such variants increases the possibility for new therapeutic interventions and clinical trial eligibility for TNBC patients. PMID- 27397725 TI - Retrospective analysis of cutaneous lesions in 23 canine and 17 feline cases of coccidiodomycosis seen in Arizona, USA (2009-2015). AB - BACKGROUND: Coccidioidomycosis is a fungal disease caused by the dimorphic saprophytic fungus Coccidioides immitis or C. posadasii. Primary pulmonary infection can disseminate to cutaneous and subcutaneous tissues, or less commonly direct cutaneous inoculation may occur. HYPOTHESIS/OBJECTIVES: To characterize the historical, clinical, diagnostic and treatment findings in dogs and cats with cutaneous manifestation of coccidioidomycosis. ANIMALS: Twenty three dogs and seventeen cats diagnosed between 2009 and 2015 in Arizona, USA. METHODS: Retrospective review of medical records from dogs and cats from an endemic area with a confirmed diagnosis via histopathology, cytology and/or culture, and skin lesions. RESULTS: Age of affected dogs ranged from 14 weeks to 13 years (median = 7 years), whereas cats ranged from 3 to 17 years (median = 9 years). Subcutaneous nodules were the most common lesions in both species. Lesions were distributed widely and not often found over sites of bone infection. In 75% of dogs and 54.5% of cats with cutaneous lesions there were clinical signs of systemic illness, supporting the diagnosis of cutaneous disseminated disease. Four dogs and four cats had localized lesions with no systemic illness, consistent with possible primary cutaneous infection. The most common mode of diagnosis was cytology identification in both species. Fluconazole was the most commonly prescribed antifungal drug. CONCLUSIONS AND CLINICAL IMPORTANCE: Coccidioidomycosis is the most common mycosis of dogs and cats in endemic regions and cutaneous signs of the disease may be an initial presenting complaint. This study identified a variety of cutaneous manifestations of the disease in dogs and cats and should be recognized by clinicians. PMID- 27397724 TI - Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease: Final Results From the International Compassionate-Use Program. AB - Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy resultswere consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose. PMID- 27397726 TI - Observed self-regulation is associated with weight in low-income toddlers. AB - Obesity emerges in early childhood and tracks across development. Self-regulation develops rapidly during the toddler years, yet few studies have examined toddlers' self-regulation in relation to concurrent child weight. Further, few studies compare child responses in food and non-food-related tasks. Our goal was to examine toddlers' observed behavioral and emotional self-regulation in food and non-food tasks in relation to their body mass index z-score (BMIz) and weight status (overweight/obese vs. not). Observational measures were used to assess self-regulation (SR) in four standardized tasks in 133 low-income children (M age = 33.1 months; SD = 0.6). Behavioral SR was measured by assessing how well the child could delay gratification for a snack (food-related task) and a gift (non food-related task). Emotional SR was measured by assessing child intensity of negative affect in two tasks designed to elicit frustration: being shown, then denied a cookie (food-related) or a toy (non-food-related). Task order was counterbalanced. BMIz was measured. Bivariate correlations and regression analyses adjusting for child sex, child race/ethnicity, and maternal education were conducted to examine associations of SR with weight. Results were that better behavioral SR in the snack delay task associated with lower BMIz (beta = 0.27, p < 0.05) and lower odds of overweight/obesity (OR = 0.66, 95% CI 0.45, 0.96), but behavioral SR in the gift task did not associate with BMIz or weight status. Better emotional SR in the non-food task associated with lower BMIz (beta = -0.27, p < 0.05), and better emotional SR in food and non-food tasks associated with lower odds of overweight/obesity (OR = 0.65, 95% CI 0.45, 0.96 and OR = 0.56, 95% CI 0.37, 0.87, respectively). Results are discussed regarding how behavioral SR for food and overall emotional SR relate to weight during toddlerhood, and regarding early childhood obesity prevention implications. PMID- 27397727 TI - Organivore or organorexic? Examining the relationship between alternative food network engagement, disordered eating, and special diets. AB - The alternative food network (AFN) refers to connections between consumers, producers, and sellers of organic, local/regional, "sustainably grown," and other artisanal and niche food not produced by the conventional system (Goodman & Goodman, 2007). Alternative foods are often viewed as the "right" consumption choice while conventional counterparts are positioned as ethically "wrong." A moral positioning of food, avoidance of certain food groups, and anxiety elicited by food consumption choices bears similarities to disordered eating behaviors (Hesse-Biber, Leavy, Quinn, & Zoino, 2006), including a newly proposed eating syndrome, orthorexia nervosa (ON; Vandereycken, 2011; Zamora, Bonaechea, Sanchez, & Rial, 2005). This study examines the relationship among engagement in the AFN, disordered eating behaviors, and special diets. We hypothesized that individuals with higher AFN engagement would be more likely report disordered eating behaviors as well as to follow a special diet. Adult men and women (N = 284) completed a series of measures assessing engagement in the AFN and eating behaviors. We found that individuals with higher AFN engagement were more likely to report ON tendencies but not significantly likely to engage in other disordered eating behaviors. Individuals following a special diet were significantly more engaged in the AFN, more likely to report ON tendencies, and more likely to self-report an eating disorder. Our findings suggest that the most engaged consumers participate in the AFN for the purported benefits reaped by society and the environment and not to moderate their consumption or mask disordered eating behaviors. Future research should prospectively explore associations between AFN engagement, ON and disordered eating behaviors, and special diets as well as consider the utility of incorporating AFN engagement into existing disordered eating prevention programs. PMID- 27397729 TI - The Role of Platelet-Derived Growth Factor Receptor in Early Brain Injury Following Subarachnoid Hemorrhage. AB - OBJECTIVE: This study aims to observe encephaledema and cell apoptosis in rats following subarachnoid hemorrhage (SAH) and to explore the mechanism of platelet derived growth factor receptor (PDGFR) in the development of early brain injury (EBI). METHODS: Adult and male Sprague-Dawley rats were randomly divided into 4 groups: sham operation, SAH, SAH + imatinib, and SAH + platelet-derived growth factor-BB (PDGF-BB). SAH model was established using intravascular silk puncture of the internal carotid artery crotch. The SAH + imatinib group was treated with intraperitoneal injection of imatinib 1 hour before establishing the model. The SAH + PDGF-BB group was administered with intracerebroventricular injection of PDGF-BB 1 hour before establishing the model. The mortality, encephaledema, and nerve functional scoring were observed after 24 hours in all groups. The expression of caspase-3 in hippocampus was tested by reverse transcription polymerase chain reaction and Western blotting. RESULTS: Mortality and encephaledema were the highest in the SAH + PDGF-BB group, which were alleviated when the rats were injected with imatinib (P < .01). CONCLUSION: PDGFR may participate in the pathogenesis of EBI following SAH. The antagonist of PDGFR, imatinib, can reduce brain damage to some degree. PMID- 27397730 TI - Gastrointestinal and nutritional problems in neurologically impaired children. AB - The current increasing survival of children with severe central nervous system damage has created a major challenge for medical care. Gastrointestinal and nutritional problems in neurologically impaired children have been recently recognized as an integral part of their disease, often leading to growth failure and worsened quality of life for both children and caregivers. Nutritional support is essential for the optimal care of these children. Undernourished handicapped children might not respond properly to intercurrent diseases and suffer unnecessarily. On the other hand, restoring a normal nutritional status results in a better quality of life in many. The easiest and least invasive method to increase energy intake is to improve oral intake. However, oral intake can be maintained as long as there is no risk of aspiration, the child is growing well and the time required to feed the child remains within acceptable limits. When oral intake is unsafe, insufficient or too time consuming, enteral nutrition should be initiated. Damage to the developing central nervous system may result in significant dysfunction in the gastrointestinal tract and is reflected in impairment in oral-motor function, rumination, gastro-oesophageal reflux (GER), with or without aspiration, delayed gastric emptying and constipation. These problems can all potentially contribute to feeding difficulty in disabled children, carrying further challenging long-term management issues. PMID- 27397732 TI - PET/CT surveillance versus neck dissection in advanced head and neck cancer. PMID- 27397731 TI - Causes of neuropathy in patients referred as "idiopathic neuropathy". PMID- 27397728 TI - Recent developments in detection and enumeration of waterborne bacteria: a retrospective minireview. AB - Waterborne diseases have emerged as global health problems and their rapid and sensitive detection in environmental water samples is of great importance. Bacterial identification and enumeration in water samples is significant as it helps to maintain safe drinking water for public consumption. Culture-based methods are laborious, time-consuming, and yield false-positive results, whereas viable but nonculturable (VBNCs) microorganisms cannot be recovered. Hence, numerous methods have been developed for rapid detection and quantification of waterborne pathogenic bacteria in water. These rapid methods can be classified into nucleic acid-based, immunology-based, and biosensor-based detection methods. This review summarizes the principle and current state of rapid methods for the monitoring and detection of waterborne bacterial pathogens. Rapid methods outlined are polymerase chain reaction (PCR), digital droplet PCR, real-time PCR, multiplex PCR, DNA microarray, Next-generation sequencing (pyrosequencing, Illumina technology and genomics), and fluorescence in situ hybridization that are categorized as nucleic acid-based methods. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are classified into immunology-based methods. Optical, electrochemical, and mass-based biosensors are grouped into biosensor based methods. Overall, these methods are sensitive, specific, time-effective, and important in prevention and diagnosis of waterborne bacterial diseases. PMID- 27397733 TI - Variants in the UBR1 gene are not associated with chronic pancreatitis in Japan. AB - BACKGROUND/OBJECTIVES: The UBR1 gene encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1. Loss-of-function mutations in the UBR1 gene cause Johanson-Blizzard syndrome, which involves pancreatic exocrine insufficiency. No previous studies have examined an association of UBR1 variants with pancreatitis, in part due to the large size of the gene. This study aimed to clarify whether UBR1 variants are associated with chronic pancreatitis (CP) by the application of targeted next generation sequencing. METHODS: Exon sequences of the UBR1 gene from 389 Japanese patients with CP (188 idiopathic, 172 alcoholic, 20 hereditary, 9 familial) were captured by the HaloPlex target enrichment technology and subjected to next generation sequencing. RESULTS: Ninety nine point two % of the coding regions of the UBR1 gene could be sequenced by >= 20 reads with a mean read depth of 595 and a median depth of 399. Fifteen non-synonymous variants including three novel ones [c.4514T > C (p.I1505T), c.4828C > G (p.H1610D) and c.4856A > T (p.D1619V)] and two synonymous variants were identified in the exonic regions. The frequency of any non-synonymous or synonymous variants was not different between the patients with CP and controls. CONCLUSIONS: Variants in the UBR1 gene were not associated with CP in Japan. PMID- 27397734 TI - Omega-3 fatty acids and mortality in patients referred for coronary angiography. The Ludwigshafen Risk and Cardiovascular Health Study. AB - BACKGROUND AND AIMS: There is an ongoing debate whether omega-3-fatty acids protect from cardiovascular disease mortality. We examined the associations of erythrocyte omega-3 fatty acids with mortality in patients referred for coronary angiography. METHODS: Erythrocyte omega-3 fatty acid proportions were measured at baseline in 3259 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) using the HS-Omega-3 Index method. Associations of omega-3 fatty acid proportions with mortality were investigated using Cox proportional hazards regression. RESULTS: During a median follow-up of 9.9 years, 975 patients (29.9%) died, 614 patients (18.8%) from cardiovascular causes. Proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were inversely associated with all-cause and cardiovascular mortality in models adjusted for conventional cardiovascular risk factors. The strongest association was observed for EPA with a hazard ratio (HR) of 0.89 (0.83-0.96) per increase of one standard deviation. Furthermore, we obtained evidence for a non-linear relation between EPA and mortality. CONCLUSIONS: EPA and DHA were associated with reduced mortality in LURIC, independent of other risk factors, with the association of EPA with mortality being non-linear. PMID- 27397735 TI - Refocusing the AIM on HDL in the metabolic syndrome. PMID- 27397736 TI - The origin of atherosclerotic plaque cells: Plasticity or not? PMID- 27397738 TI - Evaluation of Pressure Stable Chip-to-Tube Fittings Enabling High-Speed Chip-HPLC with Mass Spectrometric Detection. AB - Appropriate chip-to-tube interfacing is an enabling technology for high-pressure and high-speed liquid chromatography on chip. For this purpose, various approaches, to connect pressure resistant glass chips with HPLC pumps working at pressures of up to 500 bar, were examined. Three side-port and one top-port connection approach were evaluated with regard to pressure stability and extra column band broadening. A clamp-based top-port approach enabled chip-HPLC-MS analysis of herbicides at the highest pressure and speed. PMID- 27397739 TI - Subspecialisation in emergency medicine: An international perspective. PMID- 27397737 TI - Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlbeta (RELMbeta) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility. AB - Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMbeta, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMbeta has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMbeta plays a complex role in immune system regulation, and the impact of loss of function of RELMbeta on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlbeta (mouse ortholog of human RETNLbeta) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMbeta leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlbeta null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. PMID- 27397740 TI - Transition metal mediated formation of dicationic diselenides stabilised by N heterocyclic carbenes: designed synthesis. AB - Reactions of the N-heterocyclic carbene derivatives of selenium(ii) dihalides, LSeX2 (X = Cl, Br; L = 1,3-dibutylbenzimidazol-2-ylidene, C15H22N2) (4b, 4b'), L'SeX2 (X = Cl, Br; L' = 1,3-di(n)propylbenzimidazol-2-ylidene, C13H18N2) (4c, 4c') and L''SeX2 (X = Cl, Br; L'' = 1,3-di(i)propylbenzimidazol-2-ylidene, C13H18N2) (4d, 4d') with iron led to the formation of dicationic diselenides, [L2Se2(2+)]2[{FeCl4}(-)]3Cl(-) (7), [L2Se2(2+)][FeBr4](-)Br(-) (8), [L'2Se2(2+)][FeCl4](-)Cl(-) (9), [L'2Se2(2+)][FeBr4](-)Br(-) (10), [L''2Se2(2+)][FeCl4](-)Cl(-) (11) and [L''2Se2(2+)][FeBr4](-)Br(-) (12). The reactions of LSeX2 with copper gave selone (LSe) complexes of cuprous halides, [(LSe)2CuBr] (13) and [(LSe)2(CuI)2] (14) respectively. However, LSeX2 (X = Cl, Br, I) (4b-4b'') on treatment with zinc gave both the dicationic diselenides, [L2Se2(2+)]Y [Y = {ZnCl3(H2O)2}(2-) (15), {ZnBr4}(2-) (17)] and complexes, [(LSe)2ZnX2] (16, 18, 20). The plausible mechanism for the formation of dicationic diselenides, [L2Se2(2+)], has been proposed and is supported by performing various test reactions. To validate these mechanisms, DFT calculations have been carried out. Interestingly, the reactions of the mixture of LSeX2/L'SeX2/L''SeX2 and L'Se(0)/L'Se(0)/L''Se(0) with metal halides (FeCl3, ZnX2; X = Cl, Br, I; CdI2, HgI2, PdCl2, and PtCl2) produced dicationic diselenides, 7-12, 15, 17 and [L2Se2(2+)]Y [Y = {ZnI4}(2-) (19), {CdI4}(2-) (22), {HgI4}(2-) (25), {PdCl4}(2-) (26), {PtCl4}(2-) (27)]. The methodology is more general than the previous method and gives better yields of [L2Se2(2+)]Y. The controlled oxidation of complexes, [(LSe)2MX2] (M = Zn, Cd, Hg; X = Cl, Br, I) (16, 18, 20, 28-32) with halogenating agents (SOCl2/Br2/I2) also gave dicationic diselenides, 15, 17, 19, 22, 25 and [L2Se2(2+)]Y [Y = {CdCl4}(2-) (21), {Hg2Cl6}(2-) (23), {HgBr4}(2-) (24)], proving to be the most general method for the synthesis of [L2Se2(2+)]. Attempted syntheses of unsymmetrical dicationic diselenides, [LSe-SeL'](2+)[FeCl4](-)Cl(-) and dicationic ditelluride, [L2Te2(2+)]2[{FeCl4}(-)]3Cl(-) by the reaction of LSeX2/LTeX2 (X = Cl, Br, I) with Fe metal were unsuccessful. This observation has been corroborated with DFT calculations. PMID- 27397742 TI - Kinetics of the Reaction of CH3O2 Radicals with OH Studied over the 292-526 K Temperature Range. AB - Reaction of methyl peroxy radicals with hydroxyl radicals, CH3O2 + OH -> CH3O + HO2 (1a) and CH3O2 + OH -> CH2OO + H2O (1b) was studied using pulsed laser photolysis coupled to transient UV-vis absorption spectroscopy over the 292-526 K temperature range and pressure 1 bar (bath gas He). Hydroxyl radicals were generated in the reaction of electronically excited oxygen atoms O((1)D), produced in the photolysis of N2O at 193.3 nm, with H2O. Methyl peroxy radicals were generated in the reaction of methyl radicals, CH3, produced in the photolysis of acetone at 193.3 nm, and subsequent reaction of CH3 with O2. Temporal profiles of OH were monitored via transient absorption of light from a DC discharge H2O/Ar low-pressure resonance lamp at ca. 308 nm. The absolute intensity of the photolysis light was determined by accurate in situ actinometry based on the ozone formation in the presence of molecular oxygen. The overall rate constant of the reaction is k1a+1b = (8.4 +/- 1.7) * 10(-11)(T/298 K)(-0.81) cm(3) molecule(-1) s(-1) (292-526 K). The branching ratio of channel 1b at 298 K is less than 5%. PMID- 27397741 TI - Six cases during 2012-2015 and literature review of Chryseobacterium indologenes infections in pediatric patients. AB - Chryseobacterium indologenes is a widespread bacteria in the environment, especially hospitals, and a rarely reported human pathogen. The lowest frequency has been reported in children under 5 years of age. Clinical manifestations of C. indologenes include nosocomial pneumoniae, biliary tract infection, peritonitis, surgical wound infection, intravascular catheter-related bacteremia, cellulitis, and primary bacteremia. There is a knowledge gap in the management of C. indologenes infections, especially pertaining children, because of multiple antibiotic resistance and limited data in the literature concerning effective empirical treatment. In the published literature, a total of 16 cases of C. indologenes infections were reported in the pediatric age group. Herein, we present our experience in 6 children with C. indologenes infections. Early and prompt management of C. indologenes infections, particularly in children with mechanic ventilation, with polymicrobial infections, and under the age of 2 years, is of major importance because these factors seem to have a negative effect on the prognosis of infections caused by C. indologenes. Ciprofloxacin and TPM-SMX may be the best therapeutic choices for a combined initial empirical treatment of the patients. PMID- 27397743 TI - The effect of an interfragmentary gap on the clinical outcome after mandibular angle fracture surgery. AB - BACKGROUND/AIM: The mandibular angle fracture occasionally widens at the lower border after surgery using a single miniplate. However, the effects of an interfragmentary gap have not been fully investigated. The aim of this study was to determine the effects of gaps caused by mandibular angle fracture surgery using a single superior border miniplate technique. MATERIAL AND METHODS: In this prospective study, the interfragmentary gap was measured by panoramic radiography and cone-beam computed tomography (CBCT) postoperatively. The width of the gap measured by panoramic radiography and CBCT scans was compared. The patients were divided into two groups based on the gap width (more or less than 1.5 mm). In CBCT scans, bucco-lingual displacement of the proximal segment was evaluated. Clinical results and complication rates were investigated according to the gap and displacement. The findings were statistically analyzed. RESULTS: Thirty-two patients were included in the study. The mean interfragmentary gap widths were 1.56 +/- 0.83 mm by panoramic radiography and 2.12 +/- 0.87 mm by CBCT scans. CBCT measured a gap width of approximately 0.5 mm wider than panoramic radiography (P = 0.001). Twenty-two patients (68.8%) had an interfragmentary gap width of >1.5 mm, and ten patients (31.2%) had a gap width of <1.5 mm. All patients had favorable occlusion at the last clinical examination. There were no statistically significant differences in intermaxillary fixation periods and complication rates (P > 0.05). One patient in the wider gap group experienced pain in the temporomandibular joint when opening the mouth. Six patients (18.8%) had lingual displacement of the proximal fragment. Displacement did not significantly influence the complication rate (P > 0.05). CONCLUSION: The presence of an interfragmentary gap after mandibular angle fracture surgery did not affect the clinical outcome. PMID- 27397744 TI - Editorial. PMID- 27397745 TI - Collaborating internationally on physician leadership education: first steps. AB - Purpose Physicians are often ill-equipped for the leadership activities their work demands. In part, this is due to a gap in traditional medical education. An emergent international network is developing a globally relevant leadership curriculum for postgraduate medical education. The purpose of this article is to share key learnings from this process to date. Design/methodology/approach The Toronto International Summit on Leadership Education for Physicians (TISLEP) was hosted by the Royal College of Physicians and Surgeons of Canada, and the University of Toronto's Faculty of Medicine and Institute of Health Policy, Management and Evaluation. Of 64 attendees from eight countries, 34 joined working groups to develop leadership competencies. The CanMEDS Competency Framework, stage of learner development and venue of learning formed the scaffold for the work. Emotional intelligence was selected as the topic to test the feasibility of fruitful international collaboration; results were presented at TISLEP 2015. Findings Dedicated international stakeholders engaged actively and constructively through defined working groups to develop a globally relevant, competency-based curriculum for physician leadership education. Eleven principles are recommended for consideration in physician leadership curriculum development. Defining common language and taxonomy is essential for a harmonized product. The importance of establishing an international network to support implementation, evaluation, sustainability and dissemination of the work was underscored. Originality/value International stakeholders are collaborating successfully on a graduated, competency-based leadership curriculum for postgraduate medical learners. The final product will be available for adaptation to local needs. An international physician leadership education network is being developed to support and expand the work underway. PMID- 27397746 TI - Collaborating internationally on physician leadership development: why now? AB - Purpose This paper aims to highlight the importance of leadership development for all physicians within a competency-based medical education (CBME) framework. It describes the importance of timely international collaboration as a key strategy in promoting physician leadership development. Design/methodology/approach The paper explores published and Grey literature around physician leadership development and proposes that international collaboration will meet the expanding call for development of leadership competencies in postgraduate medical learners. Two grounding frameworks were used: complexity science supports adding physician leadership training to the current momentum of CBME adoption, and relational cultural theory supports the engagement of diverse stakeholders in multiple jurisdictions around the world to ensure inclusivity in leadership education development. Findings An international collaborative identified key insights regarding the need to frame physician leadership education within a competency based model. Practical implications International collaboration can be a vehicle for developing a globally relevant, generalizable physician leadership curriculum. This model can be expanded to encourage innovation, scholarship and program evaluation. Originality/value A competency-based leadership development curriculum is being designed by an international collaborative. The curriculum is based on established leadership and education frameworks. The international collaboration model provides opportunities for ongoing sharing, networking and diversification. PMID- 27397747 TI - Exploring valid and reliable assessment methods for care management education. AB - Purpose It is assumed that the use of valid and reliable assessment methods can facilitate the development of medical residents' management and leadership competencies. To justify this assertion, the perceptions of an expert panel of health care leaders were explored on assessment methods used for evaluating care management (CM) development in Dutch residency programs. This paper aims to investigate how assessors and trainees value these methods and examine for any inherent benefits or shortcomings when they are applied in practice. Design/methodology/approach A Delphi survey was conducted among members of the platform for medical leadership in The Netherlands. This panel of experts was made up of clinical educators, practitioners and residents interested in CM education. Findings Of the respondents, 40 (55.6 per cent) and 31 (43 per cent) participated in the first and second rounds of the Delphi survey, respectively. The respondents agreed that assessment methods currently being used to measure residents' CM competencies were weak, though feasible for use in many residency programs. Multi-source feedback (MSF, 92.1 per cent), portfolio/e-portfolio (86.8 per cent) and knowledge testing (76.3 per cent) were identified as the most commonly known assessment methods with familiarity rates exceeding 75 per cent. Practical implications The findings suggested that an "assessment framework" comprising MSF, portfolios, individual process improvement projects or self reflections and observations in clinical practice should be used to measure CM competencies in residents. Originality/value This study reaffirms the need for objective methods to assess CM skills in post-graduate medical education, as there was not a single assessment method that stood out as the best instrument. PMID- 27397748 TI - Can complexity science inform physician leadership development? AB - Purpose The purpose of this paper is to describe research that examined physician leadership development using complexity science principles. Design/methodology/approach Intensive interviewing of 21 participants and document review provided data regarding physician leadership development in health-care organizations using five principles of complexity science (connectivity, interdependence, feedback, exploration-of-the-space-of possibilities and co-evolution), which were grouped in three areas of inquiry (relationships between agents, patterns of behaviour and enabling functions). Findings Physician leaders are viewed as critical in the transformation of healthcare and in improving patient outcomes, and yet significant challenges exist that limit their development. Leadership in health care continues to be associated with traditional, linear models, which are incongruent with the behaviour of a complex system, such as health care. Physician leadership development remains a low priority for most health-care organizations, although physicians admit to being limited in their capacity to lead. This research was based on five principles of complexity science and used grounded theory methodology to understand how the behaviours of a complex system can provide data regarding leadership development for physicians. The study demonstrated that there is a strong association between physician leadership and patient outcomes and that organizations play a primary role in supporting the development of physician leaders. Findings indicate that a physician's relationship with their patient and their capacity for innovation can be extended as catalytic behaviours in a complex system. The findings also identified limiting factors that impact physicians who choose to lead, such as reimbursement models that do not place value on leadership and medical education that provides minimal opportunity for leadership skill development. Practical Implications This research provides practical applications for physician leadership development and emphasizes that it is incumbent upon physicians and organizations to focus attention on this to achieve improved patient and organizational outcomes. Originality/value This study pairing complexity science and physician leadership represents a unique way to view the development of physician leaders within the context of the complex system that is health care. PMID- 27397749 TI - In their own words: describing Canadian physician leadership. AB - Purpose This is the first study to compile statistical data to describe the functions and responsibilities of physicians in formal and informal leadership roles in the Canadian health system. This mixed-methods research study offers baseline data relative to this purpose, and also describes physician leaders' views on fundamental aspects of their leadership responsibility. Design/methodology/approach A survey with both quantitative and qualitative fields yielded 689 valid responses from physician leaders. Data from the survey were utilized in the development of a semi-structured interview guide; 15 physician leaders were interviewed. Findings A profile of Canadian physician leadership has been compiled, including demographics; an outline of roles, responsibilities, time commitments and related compensation; and personal factors that support, engage and deter physicians when considering taking on leadership roles. The role of health-care organizations in encouraging and supporting physician leadership is explicated. Practical implications The baseline data on Canadian physician leaders create the opportunity to determine potential steps for improving the state of physician leadership in Canada; and health-care organizations are provided with a wealth of information on how to encourage and support physician leaders. Using the data as a benchmark, comparisons can also be made with physician leadership as practiced in other nations. Originality/value There are no other research studies available that provide the depth and breadth of detail on Canadian physician leadership, and the embedded recommendations to health-care organizations are informed by this in-depth knowledge. PMID- 27397750 TI - Developing Canadian physician: the quest for leadership effectiveness. AB - Purpose The purpose of this study is to discern the physicians' perception of leadership effectiveness in their clinical and non-clinical roles (leadership) by identifying their political skill levels. Design/methodology/approach A sample of 209 Canadian physicians was surveyed using the Political Skills Inventory (PSI) during the period 2012-2014. The PSI was chosen because it assesses leadership effectiveness on four dimensions: social astuteness, interpersonal influence, networking ability and apparent authenticity. Findings Physicians in clinical roles' PSI scores were significantly lower in all four PSI dimensions when compared to all other physicians in non-clinical roles, with the principal difference being in their networking abilities. Practical implications More emphasis is needed on educating and training physicians, specifically in the areas of political skills, in current clinical roles if they are to assume leadership roles and be effective. Originality/value Although this study is located in Canada, the study design and associated findings may have implications to other areas and countries wanting to increase physician leadership effectiveness. Further, replication of this study in other settings may provide insight into the future design of physician leadership training curriculum. PMID- 27397751 TI - The role of the physician in transforming the culture of healthcare. AB - Purpose The healthcare system in the USA is undergoing unprecedented change and its share of unintended consequences. This paper explores the leadership role of the physician in transforming the present culture of healthcare to restore, refine and preserve its traditional care components. Design/methodology/approach The literature on change, organizational culture and leadership is leveraged to describe the structural interdependencies and dynamic complexity of the present healthcare system and to suggest how physicians can strengthen the care components of the healthcare culture. Findings When an organization's culture does not support internal integration and external adaptation, it is the responsibility of leadership to transform it. Leaders can influence culture to strengthen the care components of the healthcare system. The centrality of professionalism in the delivery of patient services places a moral, societal and ethical responsibility on physicians to lead a revitalization of the care culture. Practical implications This paper focuses on cultural issues in healthcare and provides options and guidance for physicians as they attempt to lead and manage the context in which services are delivered. Originality/value The Competing Values Framework, the major interdependent domains and five principal mechanisms for leaders to embed and fine tune culture serve as the main tenets for describing the ongoing changes in healthcare and defining the role of the physician as leaders and advocates for the Patient Care Culture. PMID- 27397752 TI - Shining the light on the dark side of medical leadership - a qualitative study in Australia. AB - Purpose The paper aims to explore the beliefs of doctors in leadership roles of the concept of "the dark side", using data collected from interviews carried out with 45 doctors in medical leadership roles across Australia. The paper looks at the beliefs from the perspectives of doctors who are already in leadership roles themselves; to identify potential barriers they might have encountered and to arrive at better-informed strategies to engage more doctors in the leadership of the Australian health system. The research question is: "What are the beliefs of medical leaders that form the key themes or dimensions of the negative perception of the 'dark side'?". Design/methodology/approach The paper analysed data from two similar qualitative studies examining medical leadership and engagement in Australia by the same author, in collaboration with other researchers, which used in-depth semi-structured interviews with 45 purposively sampled senior medical leaders in leadership roles across Australia in health services, private and public hospitals, professional associations and health departments. The data were analysed using deductive and inductive approaches through a coding framework based on the interview data and literature review, with all sections of coded data grouped into themes. Findings Medical leaders had four key beliefs about the "dark side" as perceived through the eyes of their own past clinical experience and/or their clinical colleagues. These four beliefs or dimensions of the negative perception colloquially known as "the dark side" are the belief that they lack both managerial and clinical credibility, they have confused identities, they may be in conflict with clinicians, their clinical colleagues lack insight into the complexities of medical leadership and, as a result, doctors are actively discouraged from making the transition from clinical practice to medical leadership roles in the first place. Research limitations/implications This research was conducted within the Western developed nation setting of Australia and only involved interviews with doctors in medical leadership roles. The findings are therefore limited to the doctors' own perceptions of themselves based on their past experiences and beliefs. Future research involving doctors who have not chosen to transition to leadership roles, or other health practitioners in other settings, may provide a broader perspective. Also, this research was exploratory and descriptive in nature using qualitative methods, and quantitative research can be carried out in the future to extend this research for statistical generalisation. Practical implications The paper includes implications for health organisations, training providers, medical employers and health departments and describes a multi-prong strategy to address this important issue. Originality/value This paper fulfils an identified need to study the concept of "moving to the dark side" as a negative perception of medical leadership and contributes to the evidence in this under-researched area. This paper has used data from two similar studies, combined together for the first time, with new analysis and coding, looking at the concept of the "dark side" to discover new emergent findings. PMID- 27397753 TI - Physician leadership in e-health? A systematic literature review. AB - Purpose This paper aims to systematically review the literature on roles of physicians in virtual teams (VTs) delivering healthcare for effective "physician e-leadership" (PeL) and implementation of e-health. Design/methodology/approach The analyzed studies were retrieved with explicit keywords and criteria, including snowball sampling. They were synthesized with existing theoretical models on VT research, healthcare team competencies and medical leadership. Findings Six domains for further PeL inquiry are delineated: resources, task processes, socio-emotional processes, leadership in VTs, virtual physician patient relationship and change management. We show that, to date, PeL studies on socio-technical dynamics and their consequences on e-health are found underrepresented in the health literature; i.e. no single empirical, theoretic or conceptual study with a focus on PeL in virtual healthcare work was identified. Research limitations/implications E-health practices could benefit from organization-behavioral type of research for discerning effective physicians' roles and inter-professional relations and their (so far) seemingly modest but potent impact on e-health developments. Practical implications Although best practices in e-health care have already been identified, this paper shows that physicians' roles in e-health initiatives have not yet received any in-depth study. This raises questions such as are physicians not yet sufficiently involved in e-health? If so, what (dis)advantages may this have for current e-health investments and how can they best become involved in (leading) e-health applications' design and implementation in the field? Originality/value If effective medical leadership is being deployed, e-health effectiveness may be enhanced; this new proposition needs urgent empirical scrutiny. PMID- 27397754 TI - Leadership training for undergraduate medical students. AB - Purpose Physicians play an important leadership role in the management and governance of the healthcare system. Yet, many physicians lack formal management and leadership training to prepare them for this challenging role. This Viewpoint article argues that leadership concepts need to be introduced to undergraduate medical students early and throughout their medical education. Design/methodology/approach Leadership is an integral part of medical practice. The recent inclusion of "Leader" competency in the CanMEDS 2015 represents a subtle but important shift from the previous "manager" competency. Providing medical students with the basics of leadership concepts early in their medical education allows them to integrate leadership principles into their professional practice. Findings The Faculty of Medicine at the Memorial University of Newfoundland (MUN) has developed an eight-module, fully online Physician Leadership Certificate for their undergraduate medical education program. This program is cited as an example of an undergraduate medical curriculum that offers leadership training throughout the 4 years of the MD program. Originality/value There are a number of continuing professional development opportunities for physicians in the area of management and leadership. This Viewpoint article challenges undergraduate medical education programs to develop and integrate leadership training in their curricula. PMID- 27397755 TI - Wound repair in Pocillopora. AB - Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals. PMID- 27397756 TI - Karyotype analysis in large sample cases from Shenyang Women's and Children's hospital: a study of 16,294 male infertility patients. AB - To explore that it is necessary to routinely detect chromosomes in infertile patients, we investigated peripheral blood lymphocyte karyotype in 16,294 male infertile patients in the north-east of China and analysed the incidence and type of chromosomal anomaly and polymorphism. G-banding karyotype analysis of peripheral blood lymphocytes was performed in 16,294 cases. Semen analysis was performed three times in all the men. PCR and FISH confirmed the presence of the SRY gene. The rate of chromosomal anomaly in the 16,294 male infertile patients was 4.15% (677/16,294). The rates of chromosomal anomaly were 0.24% in normal semen group, 12.6% in light oligoasthenospermia group, 4.7% in moderate-to-severe oligoasthenospermia group and 9.59% in azoospermia group. There are two male infertile patients with 45,X chromosome karyotype. One X male patient had confirmed the presence of the SRY gene and FISH analysis demonstrated its location on the p arm of chromosome 13. The other X male patient had not found SRY gene in its whole-genome DNA. Meanwhile, sperm motility is slightly oligo asthenozoospermic at the age of 35-39 and nearly azoospermic at the age of 40-45. As the rates of chromosomal anomaly are 0.24% and 12.6% even in normal semen group and light oligoasthenospermia group, the rates of chromosomal polymorphism are 5.36% and 25.51% in normal semen group and light oligoasthenospermia group, respectively; it is necessary to explore peripheral blood lymphocyte karyotype in all infertile couples. We mentioned that Y, 1, 2, 9 and 12 chromosomes were quite important about male infertility. These findings demonstrate that autosomal retention of SRY can be submicroscopic and emphasise the importance of PCR and FISH in the genetic workup of the monosomic X male. At the same time, it suggested that male infertility might be related to meiotic disturbances with spermatogenetic arrest in Y-autosome translocations, which could result in infertility by reduction of sperm production. Last but not least, ageing is one of the factors that could reduce sperm motility and quality. PMID- 27397757 TI - Pain after discharge following head and neck surgery in children. AB - BACKGROUND: It is well established that children experience significant pain for a considerable period following adenotonsillectomy. Less is known, however, about pain following other common head and neck operations. AIM: The aim of this study was to describe the severity and duration of postoperative pain experienced by children undergoing elective head and neck procedures (primary outcomes). Behavioral disturbance, nausea and vomiting, parental satisfaction, and medical reattendance rates were also measured (secondary outcomes). METHOD: Parents of children (0-18 years) undergoing common head and neck operations were invited to participate. Pain scores on the day of surgery and each day post discharge were collected via multiple telephone interviews. Data collected included pain levels, analgesia prescribed and given, behavioral disturbance rates, and nausea and vomiting scores. Follow-up was continued until pain resolved. RESULTS: Two hundred and fifty-one patients were analyzed (50 adenoidectomy, 51 adenotonsillectomy, 19 myringoplasty, 52 myringotomy, 43 strabismus, and 36 tongue tie divisions). On the day of surgery myringoplasty, strabismus surgery, and adenotonsillectomy patients on average had moderate pain, whereas adenoidectomy, tongue tie, and myringotomy patients had mild pain. Adenotonsillectomy patients continued to have moderate pain for several days with pain lasting on average 9 days. From day 1 postoperatively mild pain was experienced in the other surgical groups with the average duration of pain varying from 1 to 3 days depending on the surgery performed. Frequency of behavioral issues closely followed pain scores for each group. Analgesic prescribing and regimes at home varied widely, both within and between the different surgical groups. Rates of nausea and vomiting following discharge were low in all groups. The overall unplanned medical reattendance rate was 16%. CONCLUSION: Adenotonsillectomy patients represent the biggest challenge in postoperative pain management of the head and neck surgeries evaluated. The low rates of pain, nausea, and vomiting reported in the days following surgery for the other procedures suggests that children can be cared for at home with simple analgesia. Discharge information and analgesia prescribing on discharge should be tailored to the operation performed. PMID- 27397759 TI - Protecting public and environmental health by understanding and communicating toxicology-The 52nd EUROTOX Congress. PMID- 27397758 TI - Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection. AB - The recent attacks with the nerve agent sarin in Syria reveal the necessity of effective countermeasures against highly toxic organophosphorus compounds. Multiple studies provide evidence that a rapid onset of antidotal therapy might be life-saving but current standard antidotal protocols comprising reactivators and competitive muscarinic antagonists show a limited efficacy for several nerve agents. We here set out to test the newly developed phosphotriesterase (PTE) mutant C23AL by intravenous (i.v.), intramuscular (i.m.; model for autoinjector) and intraosseous (i.o.; model for intraosseous insertion device) application in an in vivo guinea pig model after VX challenge (~2LD50). C23AL showed a Cmax of 0.63MUmolL(-1) after i.o. and i.v. administration of 2mgkg(-1) providing a stable plasma profile up to 180min experimental duration with 0.41 and 0.37MUmolL(-1) respectively. The i.m. application of C23AL did not result in detectable plasma levels. All animals challenged with VX and subsequent i.o. or i.v. C23AL therapy survived although an in part substantial inhibition of erythrocyte, brain and diaphragm AChE was detected. Theoretical calculation of the time required to hydrolyze in vivo 96.75% of the toxic VX enantiomer is consistent with previous studies wherein similar activity of plasma containing catalytic scavengers of OPs resulted in non-lethal protection although accompanied with a variable severity of cholinergic symptoms. The relatively low C23AL plasma level observed immediately after its i.v. or i.o load, point at a possible volume of distribution greater than the guinea pig plasma content, and thus underlines the necessity of in vivo experiments in antidote research. In conclusion the i.o. application of PTE is efficient and resulted in comparable plasma levels to the i.v. application at a given time. Thus, i.o. vascular access systems could improve the post-exposure PTE therapy of nerve agent poisoning. PMID- 27397760 TI - Effects of ceftaroline on the innate immune and on the inflammatory responses of bronchial epithelial cells exposed to cigarette smoke. AB - The tobacco smoking habit interferes with the innate host defence system against infections. Recurrent infections accelerated the functional respiratory decline. The present study assessed the effects of ceftaroline on TLR2 and TLR4 and on pro inflammatory responses in airway epithelial cells (16HBE cell line and primary bronchial epithelial cells) with or without cigarette smoke extracts (CSE 10%). TLR2, TLR4, LPS binding and human beta defensin 2 (HBD2) were assessed by flow cytometry, NFkB nuclear translocation by western blot analysis, IL-8 and HBD2 mRNA by Real Time PCR; the localization of NFkB on the HBD2 and IL-8 promoters by ChiP Assay. CSE increased TLR4, TLR2 expression, LPS binding and IL-8 mRNA; CSE decreased HBD2 (protein and mRNA), activated NFkB and promoted the localization of NFkB on IL-8 promoter and not on HBD2 promoter. Ceftaroline counteracted the CSE effect on TLR2 expression, on LPS binding, on IL-8 mRNA, HBD2 and NFkB in 16HBE. The effects of ceftaroline on HBD2 protein and on IL-8 mRNA were confirmed in primary bronchial epithelial cells. In conclusion, ceftaroline is able to counteract the effects of CSE on the innate immunity and pro-inflammatory responses modulating TLR2, LPS binding, NFkB activation and activity, HBD2 and IL 8 expression in bronchial epithelial cells. PMID- 27397761 TI - Engaging South Australian local governments in the development of healthy eating policies. AB - Issue addressed Local governments are uniquely placed to influence the food environment of their communities through healthy eating policies (HEPs) but very few have done so. Methods Using a community-based participatory approach, Healthy Eating Local Policies and Programs built the capacity of South Australian local governments to develop and implement a HEP by leading the development of a HEP framework then mentoring local governments to develop their own local policy tailored to their community. Results Over a 2-year period, 31 of the 68 local governments worked towards developing a HEP, with 14 receiving endorsement by December 2013. Conclusions Local governments are ready to model healthy eating practices and adopt healthy eating policy that supports the health of their communities. A HEP developed using a participatory approach and with the flexibility to be tailored to local preferences and demographics appears feasible, although the process may be lengthy. This process and outcome appears applicable and transferable to other local governments. So what? As local governments take up their responsibilities in promoting health and wellbeing, HEPs provide important structural mechanisms to enable councils to facilitate healthy eating in their local communities. PMID- 27397762 TI - General Force-Field Parametrization Scheme for Molecular Dynamics Simulations of Conjugated Materials in Solution. AB - We describe a general scheme to obtain force-field parameters for classical molecular dynamics simulations of conjugated polymers. We identify a computationally inexpensive methodology for calculation of accurate intermonomer dihedral potentials and partial charges. Our findings indicate that the use of a two-step methodology of geometry optimization and single-point energy calculations using DFT methods produces potentials which compare favorably to high level theory calculation. We also report the effects of varying the conjugated backbone length and alkyl side-chain lengths on the dihedral profiles and partial charge distributions and determine the existence of converged lengths above which convergence is achieved in the force-field parameter sets. We thus determine which calculations are required for accurate parametrization and the scope of a given parameter set for variations to a given molecule. We perform simulations of long oligomers of dioctylfluorene and hexylthiophene in explicit solvent and find peristence lengths and end-length distributions consistent with experimental values. PMID- 27397763 TI - Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist. AB - 5-hydroxytryptamine (5-HT) is a key regulator of muscle contraction in parasitic flatworms. In Schistosoma mansoni, the myoexcitatory action of 5-HT is effected through activation of a serotonergic GPCR (Sm.5HTRL), prioritizing pharmacological characterization of this target for anthelmintic drug discovery. Here, we have examined the effects of several aporphine alkaloids on the signaling activity of a heterologously expressed Sm.5HTRL construct using a cAMP biosensor assay. Four structurally related natural products - nuciferine, D glaucine, boldine and bulbocapnine - were demonstrated to block Sm.5HTRL evoked cAMP generation with the potency of GPCR blockade correlating well with the ability of each drug to inhibit contractility of schistosomule larvae. Nuciferine was also effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. These data advance our understanding of structure-affinity relationships at Sm.5HTRL, and demonstrate the effectiveness of Sm.5HTRL antagonists as hypomotility-evoking drugs across different parasite life cycle stages. PMID- 27397765 TI - Carbon Monoxide Poisoning Caused by Water Pipe Smoking: A Case Series. AB - BACKGROUND: Carbon monoxide-related symptoms caused by water pipe smoking may be a frequent occurrence. This might often be overlooked, because patients will not always identify the smoke exposure as the cause of their presenting complaints and may well withhold this information. CASE REPORT: A series of three patients who were 15 to 28 years of age presented to the emergency department with nonspecific symptoms and were found to have carbon monoxide poisoning from water pipe smoking. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case series might improve recognition of this phenomenon. Carbon monoxide poisoning can cause serious problems, yet it could be easily diagnosed and treated. Identifying this condition can expedite treatment and prevent unnecessary diagnostic tests in an attempt to explain its symptoms. PMID- 27397764 TI - Kinetic profiling an abundantly expressed planarian serotonergic GPCR identifies bromocriptine as a perdurant antagonist. AB - The diversity and uniqueness of flatworm G protein coupled receptors (GPCRs) provides impetus for identifying ligands useful as tools for studying flatworm biology, or as therapeutics for treating diseases caused by parasitic flatworm infections. To catalyse this discovery process, technologies optimized for mammalian GPCR high throughput screening need be transposed for screening flatworm GPCRs. Here, we demonstrate the utility of a genetically encoded cAMP biosensor for resolving the properties of an abundantly expressed planarian serotonergic GPCR (S7.1R). Application of this methodology resolved the real time kinetics of GPCR modulation by ligands and demonstrated a marked difference in the kinetic action of antagonists at S7.1R. Notably, bromocriptine caused a protracted inhibition of S7.1R activity in vitro and a protracted paralysis of planarian movement, replicating the effect of S7.1R in vivo RNAi. The lengthy inhibition of function caused by bromocriptine at this abundantly expressed GPCR provides a useful tool to ablate serotonergic signaling in vivo, and is a noteworthy feature for exploitation as an anthelmintic vulnerability. PMID- 27397766 TI - The Midline Catheter: A Clinical Review. AB - BACKGROUND: Venous access in the emergency department (ED) is an often under appreciated procedural skill given the frequency of its use. The patient's clinical status, ongoing need for laboratory investigation, and intravenous therapeutics guide the size, type, and placement of the catheter. The availability of trained personnel and dedicated teams using ultrasound-guided insertion techniques in technically difficult situations may also impact the selection. Appropriate device selection is warranted on initial patient contact to minimize risk and cost. OBJECTIVE: To compare venous access device indications and complications, highlighting the use of midline catheters as a potentially cost-effective and safe approach for venous access in the ED. DISCUSSION: Midline catheters (MC) offer a comparable rate of device-related bloodstream infection to standard peripheral intravenous catheters (PIV), but with a significantly lower rate than peripherally inserted central catheters (PICC) and central venous catheters (CVC) (PIV 0.2/1000, MC 0.5/1000, PICC 2.1-2.3/1000, CVC 2.4-2.7/1000 catheter days). The average dwell time of a MC is reported as 7.69-16.4 days, which far exceeds PIVs (2.9-4.1 days) and is comparable to PICCs (7.3-16.6 days). Cost of insertion of a MC has been cited as comparable to three PIVs, and their use has been associated with significant cost savings when placed to avoid prolonged central venous access with CVCs or in patients with difficult-to-access peripheral veins. Placement of a MC includes modified Seldinger and accelerated, or all-in-one, Seldinger techniques with or without ultrasound guidance, with a high rate of first-attempt success. CONCLUSION: The MC is a versatile venous access device with a low complication rate, long dwell time, and high rate of first-attempt placement. Its utilization in the ED in patients deemed to require prolonged hospitalization or to have difficult-to-access peripheral vasculature could reduce cost and risk to patients. PMID- 27397767 TI - Heart transplantation after Fontan: Results from a surgical Fontan cohort. AB - We performed a retrospective review of outcomes after heart transplantation during long-term follow-up of a surgical cohort of 1138 Fontan patients who were followed at the Mayo Clinic. Follow-up information was obtained from medical records and a clinical questionnaire that was mailed to patients not known to be deceased at the initiation of the study. Forty-four of 1138 Fontan patients with initial or subsequent evaluation at Mayo had cardiac transplantation between 1988 and 2014 (mean age at transplantation was 23.2 +/- 12 yr, median was 19.8 yr; mean interval between Fontan and transplantation was 13.0 +/- 7.7 yr, median was 13.1 yr). Two patients had combined organ transplantation (one heart-lung, one heart-liver). Twelve of the 44 (27%) patients had PLE prior to transplantation. There was no difference in post-bypass Fontan pressures or incidence of late reoperations for AVV repair/replacement between transplanted and non-transplanted patients. There were 16 (36%) deaths in the transplantation cohort; seven occurred within 30 days of transplantation. Overall one, five, 10, and 15 yr post transplantation survival was 80%, 72%, 69%, and 55%, respectively. Although this is a challenging group of patients, intermediate-term results suggest that cardiac transplantation remains a reasonable option for patients with a failed Fontan circulation. PMID- 27397769 TI - ISPW 2016 Aberdeen - Foreword. PMID- 27397768 TI - Spiritual care as a response to an exaptation: how evolutionary psychology informs the debate. AB - This article has its origins in a 2013 proposal by the author that the concept of 'spiritual care' in clinical settings might fruitfully be grounded in the findings of the Cognitive Science of Religion (CSR). In a recent paper, John Paley rejects the central arguments and asserts his conviction that a model for 'spiritual care' cannot be derived from the insights of evolutionary psychology. In this article, the author employs a modified form of Fichtean dialectic to examine the contrasting positions and, via a process of analysis and synthesis, identify the key areas for further exploration and research. He concludes, first, that CSR in itself does not provide a sufficient theoretical justification for the notion and practice of 'spiritual care'; secondly, that any attempt to develop a general theory of spiritual care would need to pay closer attention to the role of historically situated religious communities; and finally, that these objections nevertheless do not amount to an argument against the attempt to provide spiritual care as part of person-centred care. Instead, a revised model is proposed which has the potential to provide testable predictions in this field. PMID- 27397770 TI - Abstracts of the 19(th) International Social Pharmacy Workshop, 19-22 July 2016, Aberdeen, UK. PMID- 27397771 TI - Anion directed structural diversity in zinc complexes with conformationally flexible quinazoline ligand: structural, spectral and theoretical studies. AB - In this paper, we report the synthesis, structure and photophysical studies of four new complexes of conformationally flexible 6-chloro-4-phenyl-2-(pyridin-2 yl)quinazoline ligand (L) with Zn(ii). The coordinating ability of the ligand and geometrical preferences of the resultant complexes are tuned by varying the anion of the metal salt as confirmed by structural and DFT studies. The choice of the metal salt (especially anion) directs the stabilisation of different conformations of the ligand arising out of twisting of the pyridyl ring with respect to the quinazoline ring, resulting in complexes with different nuclearity (monomer/dimer) as well as different coordination geometries (tetrahedral/trigonal bipyramidal/octahedral). Photophysical properties are also found to be tuned due to conformational changes on complexation. DFT studies on the ligand establish the conformationally stable forms as observed in the reported structures. PMID- 27397772 TI - When the doctor is sick too. PMID- 27397773 TI - Syria: a health crisis too great to ignore. PMID- 27397774 TI - Substance use in young people. PMID- 27397775 TI - The French experience of the threat posed by Zika virus. PMID- 27397777 TI - The Wakley Prize, 2016: take us on a journey. PMID- 27397779 TI - US law agencies target "high prescribers" of pain relief. PMID- 27397780 TI - Drug development partnerships look set to grow. PMID- 27397781 TI - Perspectives on mortality. PMID- 27397782 TI - Julie Makani: at the cutting edge of sickle-cell disease. PMID- 27397783 TI - The Hajj health requirements: changing a mindset. PMID- 27397784 TI - Happiness, health, and mortality. PMID- 27397785 TI - Happiness, health, and mortality. PMID- 27397786 TI - Happiness, health, and mortality - Authors' reply. PMID- 27397787 TI - Happiness, health, and mortality. PMID- 27397788 TI - Post-sanctions era in Iran: opportunity for science and publication. PMID- 27397789 TI - Caesarean section in Iran. PMID- 27397790 TI - Post-sanctions era in Iran: opportunity for science and publication. PMID- 27397791 TI - Bilateral lower limb weakness in acute severe ulcerative colitis. PMID- 27397792 TI - The inherent dangers of high-dose steroids for acute inflammatory conditions. PMID- 27397793 TI - Human chorionic gonadotrophin in early gestation induces growth of estrogenic ovarian follicles and improves primiparous sow fertility during summer. AB - Reduced summer farrowing rates may be due to inadequate corpora luteal (CL) support. Porcine CL become dependent on LH from 12 d of pregnancy and the embryonic estrogen signal for maternal recognition of pregnancy (MRP) is initiated at about 11-12 d after insemination. We hypothesised that injection of the LH analogue human chorionic gonadotropin (hCG) would induce growth of estrogenic follicles and, by mimicking the signal for MRP and stimulating progesterone secretion, increase primiparous sow fertility. In Experiment 1, during a 28 d lactation 53 mixed parity sows were full-fed either throughout lactation (n=16) or until 18 d and then feed restricted during the last 10 d of lactation (n=36). At 12 d after mating restrict-fed sows were injected with 1000IU hCG (n=17) or were not injected (n=19); the full-fed sows acted as non treated positive controls. Transrectal ovarian ultrasound exams were performed on days 12, 16, 20, 24, and 28; blood samples were obtained on days 12, 14, and 15 for estradiol and progesterone assay. For Experiment 2, during the summer months primiparous sows received 1000IU hCG 12 d after mating (n=28) or were non injected controls (n=27). Pregnancy status was determined at 28 d and sows allowed to go to term to determine farrowing rates and litter sizes. In Experiment 1, injection of hCG increased (P<0.001) follicle diameter and serum concentrations of estradiol (P<0.01) and progesterone (P<0.05). There were no effects of lactation feeding level on wean-estrus interval, farrowing rate or subsequent litter size. In Experiment 2, hCG injection was associated with a higher pregnancy rate (P<0.05) and farrowing rate (P<0.08). There was no effect on litter size. These data confirm that hCG stimulates growth of estrogenic follicles and CL function, and improves primiparous sow fertility during the summer months. PMID- 27397795 TI - Complete genome sequence of bacteriophage P2559Y, a marine phage that infects Croceibacter atlanticus HTCC2559. AB - The genus Croceibacter of the family Flavobacteriaceae represents a ubiquitous component of marine bacterioplankton, and is known to be involved in the interaction with phytoplankton. Here, we report the isolation and genome sequencing of a lytic siphovirus P2559Y that infects Croceibacter atlanticus HTCC2559, the type strain of the genus Croceibacter. The complete genome of P2559Y was 43,153bp in length, with a GC content of 38.9%. Functional annotation of 51 genes predicted in the genome showed that the P2559Y genome had a modular architecture. Comparison to the genome of P2559S, another phage that infects the same host strain, revealed an interesting feature in the genetic diversity of phages infecting the genus Croceibacter. The two phage genomes had a synteny in the structure module and shared many structural genes, while little similarity was found in the DNA replication/metabolism module. PMID- 27397794 TI - Associations between hypo-HDL cholesterolemia and cardiometabolic risk factors in middle-aged men and women: Independence of habitual alcohol drinking, smoking and regular exercise. AB - OBJECTIVE: Hypo-HDL cholesterolemia is a potent cardiovascular risk factor, and HDL cholesterol level is influenced by lifestyles including alcohol drinking, smoking and regular exercise. The aim of this study was to clarify the relationships between hypo-HDL cholesterolemia and cardiovascular risk factors and to determine whether or not these relationships depend on the above-mentioned lifestyles. METHODS: The subjects were 3456 men and 2510 women (35-60 years of age) showing low HDL cholesterol levels (<40mg/dl for men and <50mg/dl for women) and their age-matched control subjects showing normal HDL cholesterol levels. Each cardiometabolic risk factor was compared between the groups with and without hypo-HDL cholesterolemia. Data for hypo-HDL cholesterolemic subjects not having habits of alcohol drinking, smoking and regular exercise (men, n=333; women, n=1410) and their age-matched control subjects were also analysed. RESULTS: Both in men and in women of overall subjects and subjects without histories of alcohol drinking, smoking and regular exercise, odds ratios of subjects with hypo-HDL cholesterolemia vs. subjects with normo-HDL cholesterolemia for high body mass index, high waist-to-height ratio, high triglycerides, high lipid accumulation product and multiple risk factors (three or more out of obesity, hypertension, dyslipidaemia and diabetes) were significantly higher than the reference level of 1.00. These associations in overall subjects were found when the above habits were adjusted. CONCLUSIONS: Hypo-HDL cholesterolemic men and women have adverse cardiovascular profiles, such as obesity, hypertriglyceridemia and multiple risk factors, independently of age, alcohol drinking, smoking and regular exercise. PMID- 27397797 TI - A parametric ribcage geometry model accounting for variations among the adult population. AB - The objective of this study is to develop a parametric ribcage model that can account for morphological variations among the adult population. Ribcage geometries, including 12 pair of ribs, sternum, and thoracic spine, were collected from CT scans of 101 adult subjects through image segmentation, landmark identification (1016 for each subject), symmetry adjustment, and template mesh mapping (26,180 elements for each subject). Generalized procrustes analysis (GPA), principal component analysis (PCA), and regression analysis were used to develop a parametric ribcage model, which can predict nodal locations of the template mesh according to age, sex, height, and body mass index (BMI). Two regression models, a quadratic model for estimating the ribcage size and a linear model for estimating the ribcage shape, were developed. The results showed that the ribcage size was dominated by the height (p=0.000) and age-sex-interaction (p=0.007) and the ribcage shape was significantly affected by the age (p=0.0005), sex (p=0.0002), height (p=0.0064) and BMI (p=0.0000). Along with proper assignment of cortical bone thickness, material properties and failure properties, this parametric ribcage model can directly serve as the mesh of finite element ribcage models for quantifying effects of human characteristics on thoracic injury risks. PMID- 27397796 TI - Psychosocial distress and its effects on the health-related quality of life of primary brain tumor patients. AB - All cancer patients experience distress from the diagnosis, the effects of the disease or the treatment. Clinically significant distress decreases overall quality of life and the recognition of distress with prompt intervention is essential. The National Comprehensive Cancer Network distress thermometer (NCCN DT) is a validated measuring tool that has been utilized in the primary brain tumor population to detect psychologic distress thereby provoking a referral process to the appropriate support system. Brain tumor patients commonly reported emotional and physical distress encompassing: fatigue, fears, memory and concentration and worry. More research is needed to identify the stressors of all primary brain tumor patients and their caretakers and integrate appropriate interventions to improve health-related quality of life in both groups. PMID- 27397798 TI - An evaluation of an aptamer for use as an affinity reagent with MS: PCSK9 as an example protein. AB - BACKGROUND: For quantitative immunoaffinity IA-LC-MS, the utility of antibodies has been demonstrated many times but the utility of aptamers as affinity reagents is unproven. METHODS: Immunoaffinity reagents including a monoclonal antibody and an aptamer were coupled to magnetic beads and used as part of an enrichment strategy for PCSK9 quantitation in plasma. RESULTS: With limited method development, we have established a comparison of an anti-PCSK9 aptamer with an anti-PCSK9 monoclonal antibody. The background that results from a tryptic digest of affinity enrichment in plasma was demonstrated for each reagent using high resolution full scan MS. The assay recovery was demonstrated for multiple concentrations of aptamer in plasma with different concentrations of PCSK9 protein. CONCLUSION: The aptamer achieved comparable enrichment to the antibody, but with lower peptide background, thus demonstrating the potential use of aptamers for IA-LC-MS. PMID- 27397799 TI - On bias and precision in meta-analysis: the error in the error. PMID- 27397800 TI - Evaluating leachate recirculation with cellulase addition to enhance waste biostabilisation and landfill gas production. AB - The effect of leachate recirculation with cellulase augmentation on municipal solid waste (MSW) biostabilisation and landfill gas production was investigated using batch bioreactors to determine the optimal conditions of moisture content, temperature and nutrients. Experimentation was thereafter scaled-up in 7L bioreactors. Three conditions were tested including (1) leachate recirculation only, (2) leachate recirculation with enzyme augmentation and (3) no leachate recirculation (control). Cumulative biogas production of the batch tests indicated that there was little difference between the leachate and control test conditions, producing on average 0.043m(3)biogaskg(-1) waste. However the addition of cellulase at 15*10(6)Utonne(-1) waste doubled the biogas production (0.074m(3)biogaskg(-1) waste). Similar trend was observed with the bioreactors. Cellulase addition also resulted in the highest COD reduction in both the waste and the leachate samples (47% and 42% COD reduction, respectively). In both cases, the quantity of biogas produced was closer to the lower value of theoretical and data-based biogas prediction indicators (0.05-0.4m(3)biogaskg(-1) waste). This was likely due to a high concentration of heavy metals present in the leachate, in particular Cr and Mn, which are known to be toxic to methanogens. The cost-benefit analysis (CBA) based on the settings of the study (cellulase concentration of 15*10(6)Utonne(-1) waste) showed that leachate bioaugmentation using cellulase is economically viable, with a net benefit of approximately ?12.1million on a 5Mt mixed waste landfill. PMID- 27397801 TI - [Do that again please?]. PMID- 27397802 TI - [Quality of life and symptoms in patients with chronic depression and anxiety after a self-management training: a randomised controlled trial]. AB - BACKGROUND: Evidence-based interventions aimed at patient rehabilitation are not readily available in outpatient mental health care for patients with chronic anxiety and/or depression. AIM: To evaluate the effects that the program 'Rehabilitation through self-management' had on the life and symptoms of patients who had received this programme for six months in an outpatient mental health care setting. METHOD: As part of a randomised controlled trial, patients were assigned to receive the programme (intervention group) or care as usual (control group). After six months we evaluated the change in the quality of life (World Health Organisation Quality of Life assessment, Brief version (WHOQOL-BREF)) and the change in anxiety symptoms (Beck Anxiety Inventory (BAI)) and depressive symptoms (Patient Health Questionnaire (PHQ-9)) using linear mixed models analysis. RESULTS: We included 141 patients from 12 participating mental health care institutions. We found no significant difference between the quality of life or symptoms of patients in the intervention group and those in the control groups. Differences in change scores on the WHOQOL-BREF, BAI and PHQ-9 were 0.74 (p=0.63), 0.39 (p=0.81) and -0.07 (p=0.95) respectively. Higher scores on the BAI and PHQ-9 had a negative influence on the effect of the intervention. CONCLUSION: After six months the programme had no significant effect on patients' quality of life or symptoms. These results reflect the chronicity of symptoms and the relation between symptoms and the quality of life in this patient population. PMID- 27397803 TI - [Schizophrenia exists: yes / no / don't know]. AB - BACKGROUND: The suggestion that schizophrenia does not exist has let to a discussion in Dutch national newspapers. According to several contributors, the diagnosis schizophrenia can wrongly lead to stigmatisation and defeatism with regard to treatment and should therefore be replaced by the broader concept, psychosis. This view strengthens the argument that 'schizophrenia does not exist'. In reaction to this view it has been suggested that in some articles that schizophrenia is now believed to have a definite biological basis. AIM: To clarify the various arguments and concepts that are used. METHOD: The arguments for and against are reviewed from an ontological perspective. Ethical/political arguments and scientific arguments are handled separately and are set against each other. RESULTS: The ontological status of psychiatric disorders, including schizophrenia, are problematic, as has been shown in a recent study by Kendler. From the perspective of the medical scientific programme - namely, try to go from syndromes to anatomically defined diseases - it would appear that one party wants to abandon this programme, whereas the other party wants to continue it. CONCLUSION: Research over the last few decades has been unable to clarify the ontological status of schizophrenia. PMID- 27397804 TI - [Red tape in psychiatry: on bureaucracy, bureaucratism, and our secret fondness for procedures]. AB - BACKGROUND: A frequent complaint in psychiatry is that the psychiatrist-patient relationship and the quality of care are hampered by bureaucratic processes. AIM: To provide an analysis of various types of bureaucracy in psychiatry that can serve as a starting-point for the improvement of care and the performance of qualitative studies. METHOD: We conducted an exploratory study using PubMed, Google, and various Dutch medical journals. RESULTS: Contemporary psychiatry is characterised by a bureaucratic organization structure. Mental, somatic, and social problems are translated in a standardised manner into medical jargon which gives rise to a DSM diagnosis, a cost-price, and outcome measures. This medical bureaucratic system has important virtues, provided it is applied efficiently and the patient-psychiatrist relationship remains intact. In the Netherlands, however, this balance has been disturbed. Future research can be facilitated if distinctions are made between various types of bureaucracy (referred to here as Hippocratic, Weberian, and Kafkaesque bureaucracy). In addition, we discuss various national initiatives which aim to counter bureaucracy, including initiatives of the Dutch government. CONCLUSION: If the patient-psychiatrist relationship is to regain its central role, bureaucracy needs to be countered constantly. The government can facilitate this process, but healthcare providers can also play a key role and meanwhile help to bring about a substantial reduction in the costs of care. PMID- 27397805 TI - [Recommendations regarding diagnosis and treatment of obsessive-compulsive symptoms in schizophrenia]. AB - BACKGROUND: Obsessive-compulsive symptoms (OCS) are common in patients with schizophrenia. Although these symptoms are associated with an unfavourable course of the illness, in many cases they are not recognised or treated. The situation for patients with schizophrenia and obsessive-compulsive disorder (OCD) could improve considerably now that more advanced diagnostic techniques and better treatment options have been available. AIM: To provide an overview of current knowledge regarding diagnosis and treatment options. METHOD: We searched the literature for relevant articles. RESULTS: With careful diagnosis OCS could be better noticed. Based on the time of onset of the OCS and the relationship between these symptoms and the use of antipsychotics, we propose a treatment strategy. CONCLUSION: Cognitive behavioural therapy, as well as various pharmacotherapeutic strategies, are promising treatment options that could deployed more frequently to treat persistent OCD in schizophrenia. Although the research findings are homogeneous, the methodological quality of the studies is still low. PMID- 27397806 TI - [Data streams and limits to the use of patient data originating in (forensic) mental health care institutions]. AB - BACKGROUND: Patient data are not being used soley in the mental health care institutions in which the patients are being treated. Discussion about the legitimacy of using patient data for various purposes is hindered by a lack of clarity about the nature and content of the data streams. AIM: To provide insight into the discrepancy between the purposes of collecting patient data and the purposes for which patient data are being used. METHOD: We reviewed literature on the subject and consulted professionals by means of (open) interviews. RESULTS: Patient data can be divided into four categories, each of which corresponds to the particular purpose for which patient data were acquired or used: clinical, quality and policy, research and 'other purposes'. CONCLUSION: The way in which patient data are handled should depend on the nature and content of the data involved and, above all, on the purposes for which the data have been collected. PMID- 27397807 TI - [An 87-year-old-man with late-onset frontotemporal dementia: a case-study]. AB - An 87-year-old man showed behavioral disinhibition and nocturnal restlessness as well as short-term memory problems. We diagnosed late-onset frontotemporal dementia (LO-FTD), a relatively rare disease. Based on the course of the disease progress, we ruled out medication-induced mania and bipolar disorder. Given the results of the CT-scan, we also dismissed the possibility that the patient was suffering from dementia based on Alzheimer's disease and vascular factors that followed an atypical course. Our article illustrates the complexity of the diagnostic process investigating LO-FTD. PMID- 27397808 TI - [Reaction on 'Guideline psychiatric diagnostics 2015: strong positioning and some loose ends' (2)]. PMID- 27397809 TI - Bacterium-Expressed dsRNA Downregulates Microsporidia Nosema bombycis Gene Expression. AB - The microsporidia Nosema bombycis is the insect pathogen of pebrine disease severely destructive to sericulture production. Here, we describe the use of Escherichia coli HT115 strain (DE3) to express double-strand RNAs targeting the gene encoding ADP/ATP protein in N. bombycis. The results showed that dsRNAs deferentially suppressed the gene expression during N. bombycis infection in the silkworm, and the effect waned gradually. Our results, for the first time, provide a tool to utilize the dsRNA expressed by recombinant E. coli to control the pebrine disease of the domestic silkworm. PMID- 27397810 TI - Guidance for using mixed methods design in nursing practice research. AB - The mixed methods approach purposefully combines both quantitative and qualitative techniques, enabling a multi-faceted understanding of nursing phenomena. The purpose of this article is to introduce three mixed methods designs (parallel; sequential; conversion) and highlight interpretive processes that occur with the synthesis of qualitative and quantitative findings. Real world examples of research studies conducted by the authors will demonstrate the processes leading to the merger of data. The examples include: research questions; data collection procedures and analysis with a focus on synthesizing findings. Based on experience with mixed methods studied, the authors introduce two synthesis patterns (complementary; contrasting), considering application for practice and implications for research. PMID- 27397811 TI - Influence of work-family-school role conflicts and social support on psychological wellbeing among registered nurses pursuing advanced degree. AB - PURPOSE: The purpose of the study was to determine how work-family-school role conflict and social support influence psychological well-being among registered nurses pursuing an advanced degree. METHODS: A cross-sectional, correlational study design was used. Convenience sampling was used to recruit 320 registered nurses pursuing an advanced nursing degree at 13 hospitals in Korea, from June to October 2011. Data were analyzed using structural equation modeling with the AMOS program. Confirmatory factor analyses were conducted to evaluate the measurement model prior to the testing of study hypotheses before and after controlling for extraneous variables. RESULTS: The fit parameters of the modified model (chi(2)/df=2.01, GFI=0.91, AGFI=0.89, CFI=0.92, SRMR=0.068, and RMSEA=0.065) indicated its suitability as the research model. This model explained 45% of the variance in work-related psychological well-being and 52% of the variance in general psychological well-being. Both social support and work-family-school role conflict exerted significant effects on work-related psychological well-being and general psychological well-being. CONCLUSION: The findings of the present study imply that work-family-school role conflict influences the psychological well being of registered nurses pursuing an advanced degree. It is necessary for nursing administrators to develop strategies to help registered nurses to manage their multiple roles and improve both their work-related psychological well-being and their general psychological well-being. PMID- 27397813 TI - Exploring the relationship between work environment, job satisfaction, and intent to stay of Jordanian nurses in underserved areas. AB - AIMS: The aims of this study are to (1) examine the relationships between work environment, job satisfaction and intention to stay at work; and (2) explore the predicting factors of intention to stay at work among nurses in underserved areas. BACKGROUND: Developing and fostering creative work environment are paramount especially in underserved areas, where the work conditions present many challenges. METHODS: A descriptive correlational design was utilized to collect data from 330 hospital nurses who worked in two underserved governorates in Jordan. A set of instruments were used to measure the variables of the study. RESULTS: The results showed a strong positive association between job satisfaction and work environment. The results of logistic regression indicated receiving housing, job satisfaction, and work environment were the predicting variables of the level of intention to stay at work. CONCLUSION: It is critical to improve work conditions and create a culture of supportive work environment in underserved area. PMID- 27397812 TI - Long-term effects of an intensive-practical diabetes education program on HbA1c and self-care. AB - OBJECTIVE: The purpose of this study was to implement an intensive and practical diabetes education program (DEP) and evaluate its long-term effects and its impact on psychosocial variables. It was hypothesized that the DEP would improve patients' metabolic control (A1c hemoglobin - HbA1c), technical knowledge, self efficacy and frequency of self-care and decrease barriers and other parameters such as the body mass index (BMI) and LDL cholesterol. These results should be maintained at one-year follow-up. DESIGN AND SETTING: The sample was composed of 40 patients with diabetes type I who attended a diabetes outpatient clinic. A repeated measures design, considering medical and psychosocial variables at six months and one year, was used. RESULTS: Results have statistical and clinical implications. They revealed significant changes that were maintained at one-year follow-up in HbA1c, barriers to self-care, frequency of self-care, knowledge about the disease and perceived self-efficacy. The areas of self-care where the fewest changes took place were diet and exercise, which are highly related to cardiovascular risk factors and are very present in patients with diabetes. Specifically, no changes were observed in BMI or LDL cholesterol. CONCLUSION: The intensive DEP proved to be effective, although specific efforts should be made in certain areas to ensure longer-lasting benefits. Besides, including not only educational but also psychological strategies in patients' education to motivate them to make real lifestyle changes should be a priority in the design of any DEP. PMID- 27397814 TI - Ineffective airway clearance in adult patients after thoracic and upper abdominal surgery. AB - AIM: The aim of this study is to analyze the accuracy of the defining characteristics of ineffective airway clearance (IAC) in patients after thoracic and upper abdominal surgery. BACKGROUND: Although numerous studies have described the most prevalent respiratory NANDA-I diagnoses, only few investigates the precision of nursing assessments. METHODS: A cross-sectional study was conducted with 192 patients in a surgical clinic. Accuracy measures were obtained by the latent class analysis method. RESULTS: IAC was present in 46.73% of the sample. The defining characteristics with better predictive capacity were changes in respiratory rate and changes in respiratory rhythm. However, other defining characteristics also had high specificity, such as restlessness, cyanosis, excessive sputum, wide-eyed, orthopnea, adventitious breathing sounds, ineffective cough, and difficulty vocalizing. CONCLUSION: Results can contribute to the improvement of nursing assessments by providing information about the key clinical indicators of IAC. PMID- 27397815 TI - Early malnutrition screening and low cost protein supplementation in elderly patients admitted to a skilled nursing facility. AB - BACKGROUND: Malnutrition among skilled nursing facility (SNF) patients can lead to hospital readmissions and multiple complications. PURPOSE: To evaluate the effect of an existing malnutrition screening and management program on prealbumin levels of patients in skilled nursing facilities. METHODS: A retrospective design was used to evaluate baseline admission data including a prealbumin level. Patients with malnutrition received an oral protein supplement according to protocol. A comparison prealbumin level was obtained at 30days. RESULTS: Nearly half of the patients were severely malnourished on admission. Patients receiving the prescribed protocol had significantly increased prealbumin levels at 30days than those patients that did not receive the protocol as prescribed. CONCLUSION: A prealbumin level upon admission at a SNF could represent a reliable tool to evaluate malnutrition. Initiation of an early malnutrition screening and protein supplement program in this setting is essential to identifying and treating at risk patients before complications occur. PMID- 27397817 TI - Structural empowerment, job stress and burnout of nurses in China. AB - PURPOSE: To investigate the status of structural empowerment, job stress and burnout in China, and to explore the relationships among them. METHODS: The questionnaires of CWEQ-II, job stressors and MBI were used to investigate 1002 nurses working at tertiary-level hospitals. RESULTS: The average score of CWEQ-II was 2.23+/-0.59. The score of EE of MBI was 29.75+/-13.94, PA was 27.40+/-11.21, both of them showed a high level of exhaustion, DP was 8.07+/-5.82 and showed a middle level of exhaustion. The findings showed that workload and time pressure were the most frequently encountered job stress among staff nurses, the score was 3.23+/-0.95; There was a significantly correlation among structural empowerment, job stressors and the level of burnout(p<0.05). Hierarchical regression analysis showed that structural empowerment had significant influence on the every factors of job stressors (p<0.05) and burnout, job stressors had significant influence on the every factors of burnout (p<0.05). Structural equation modeling analyses revealed a good fit to the data based on various fit indices (chi(2)/df=2.29, GFI=0.945, CFI=0.965, IFI=0.966, RMSEA=0.061). Staff nurses felt that structural empowerment in their workplace resulted in lower levels of job stress which in turn strongly influenced Burnout. CONCLUSIONS: These results provide initial support for an expanded model of structural empowerment, and offer a broader understanding of the empowerment process. PMID- 27397816 TI - Fall risk assessment: retrospective analysis of Morse Fall Scale scores in Portuguese hospitalized adult patients. AB - PURPOSE: The Morse Fall Scale is used in several care settings for fall risk assessment and supports the implementation of preventive nursing interventions. Our work aims to analyze the Morse Fall Scale scores of Portuguese hospitalized adult patients in association with their characteristics, diagnoses and length of stay. METHODS: Retrospective cohort analysis of Morse Fall Scale scores of 8356 patients hospitalized during 2012. Data were associated to age, gender, type of admission, specialty units, length of stay, patient discharge, and ICD-9 diagnosis. RESULTS: Elderly patients, female, with emergency service admission, at medical units and/or with longer length of stays were more frequently included in the risk group for falls. ICD-9 diagnosis may also be an important risk factor. CONCLUSIONS: More than a half of hospitalized patients had "medium" to "high" risk of falling during the length of stay, which determines the implementation and maintenance of protocoled preventive nursing interventions throughout hospitalization. There are several fall risk factors not assessed by Morse Fall Scale. There were no statistical differences in Morse Fall Scale score between the first and the last assessment. PMID- 27397818 TI - Evidence-based nursing practice and its correlates among Korean nurses. AB - AIM: The aim of the study was to explore evidence-based nursing practice (EBNP) in Korean and identify factors influencing its implementation. BACKGROUND: EBNP is relatively new in Korea, and there is a lack of consistency about the factors that affect EBNP implementation. METHODS: A descriptive correlational and cross sectional design was employed and a convenience sample of 392 nurses were recruited from two general hospitals. Data were analyzed by using descriptive and inferential statistics. RESULTS: The overall model significantly explained 17.1% of variance in EBNP implementation. Among the predictors of EBNP implementation, regularly reading research articles, level of searching skills for literature, degree of understanding EBNP, professional autonomy, and EBNP beliefs had statistically significant influences on EBNP implementation. CONCLUSION: Findings suggest the necessity for Korean nurses to regularly read research articles, develop greater skills in developing searching research documents, gain clearer understanding of EBNP, EBNP beliefs, and particularly, high level of professional autonomy. PMID- 27397819 TI - The effect of a translating research into practice intervention to promote use of evidence-based fall prevention interventions in hospitalized adults: A prospective pre-post implementation study in the U.S. AB - BACKGROUND: Falls are a major public health problem internationally. Many hospitals have implemented fall risk assessment tools, but few have implemented interventions to mitigate patient-specific fall risks. Little research has been done to examine the effect of implementing evidence-based fall prevention interventions to mitigate patient-specific fall risk factors in hospitalized adults. OBJECTIVES: To evaluate the impact of implementing, in 3 U.S. hospitals, evidence-based fall prevention interventions targeted to patient-specific fall risk factors (Targeted Risk Factor Fall Prevention Bundle). Fall rates, fall injury rates, types of fall injuries and adoption of the Targeted Risk Factor Fall Prevention Bundle were compared prior to and following implementation. DESIGN: A prospective pre-post implementation cohort design. SETTING: Thirteen adult medical-surgical units from three community hospitals in the Midwest region of the U.S. PARTICIPANTS: Nurses who were employed at least 20hours/week, provided direct patient care, and licensed as an RN (n=157 pre; 140 post); and medical records of patients 21years of age or older, who received care on the study unit for more than 24hours during the designated data collection period (n=390 pre and post). METHODS: A multi-faceted Translating Research Into Practice Intervention was used to implement the Targeted Risk Factor Fall Prevention Bundle composed of evidence-based fall prevention interventions designed to mitigate patient-specific fall risks. Dependent variables (fall rates, fall injury rates, fall injury type, use of Targeted Risk Factor Fall Prevention Bundle) were collected at baseline, and following completion of the 15month implementation phase. Nurse questionnaires included the Stage of Adoption Scale, and the Use of Research Findings in Practice Scale to measure adoption of evidence-based fall prevention practices. A Medical Record Abstract Form was used to abstract data about use of targeted risk-specific fall prevention interventions. Number of falls, and number and types of fall injuries were collected for each study unit for 3months pre- and post-implementation. Data were analyzed using multivariate analysis. RESULTS: Fall rates declined 22% (p=0.09). Types of fall injuries changed from major and moderate to minor injuries. Fall injury rates did not decline. Use of fall prevention interventions improved significantly (p<0.001) for mobility, toileting, cognition, and risk reduction for injury, but did not change for those targeting medications. CONCLUSIONS: Using the Translating Research Into Practice intervention promoted use of many evidence-based fall prevention interventions to mitigate patient-specific fall risk factors in hospitalized adults. PMID- 27397820 TI - Acceptance of home support and integrated care among advanced COPD patients who live outside large medical centers. AB - BACKGROUND: Poor self-management constitutes a risk factor for COPD deterioration. Patients from rural areas located at a considerable distance from large medical centers frequently need home-support in advanced stages of the disease. Integrated care has been proposed as a comprehensive model for appropriate treatment, coordination and holistic support. The aim of the study was to assess whether home visits provided by trained assistants are needed and accepted by advanced COPD patients living in rural areas a to evaluate whether an individual short educational program can actually improve such patients' knowledge of COPD and inhaler use. METHODS: Thirty patients with severe or very severe but stable COPD participated in one-month home-assistance interventions twice a week. RESULTS: The total value >=70 of SGRQ (St George's Respiratory Questionnaire) was recorded in 18 (60%) patients. At the beginning of the study, the patients' knowledge of COPD and inhalation techniques was highly unsatisfactory. Significant improvement in all items (p=0.00) was obtained after the intervention. The risk for poor self-management was high. All patients had at least one 'factor' that indicated the need for home-support. A total of 240 visits (100%) were completed. Patients expressed high acceptance for home-based support delivered by medical assistants twice a week for one month. No patients opposed this kind of care and most of them expressed interest in receiving it in the future. CONCLUSIONS: The results suggest a compelling need for home care and demonstrate full acceptance of this kind of support on the part of advanced COPD patients. PMID- 27397821 TI - Characteristics of the middle-age adult inpatient fall. AB - PURPOSE: The purpose of this study is to describe characteristics of middle-age inpatients' (ages 45-64) fallers and their fall and fall injury risk factors. BACKGROUND: Middle-age falls were 42-46% of inpatient falls. Studies related to inpatient falls have not targeted this population. METHODS: A 439 retrospective chart review was performed. Middle-age fall and injury rates were compared with ages 21-44 and 65-90. RESULTS: The mean age was 55.75years (SD 5.26). 28.7% (n=126) of falls resulted in injury. Individual fallers (n=386) had a mean of four comorbidities (SD 1.843), including hypertension (46.5%), anxiety/depression (40.2%), and alcohol and drug abuse (32.9%). There was no significant difference (p=.637) in fall rates per 1,000 patient days between ages 45-64 and 65-90. CONCLUSION: Middle-age inpatients' acute illness makes them as vulnerable for fall and injury as the older population. They should not be overlooked for fall prevention measures. PMID- 27397822 TI - Education for medications and side effects: a two part mechanism for improving the patient experience. AB - AIM: A nursing study aimed to increase patient understanding of new medications and their side effects, and positively impact Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey scores for medications communication. BACKGROUND: Hospital patients' understanding of new medications and side effects is a major satisfaction indicator when formal surveys serve as quality measures. Medical/surgical unit survey scores at a 328-bed Texas hospital were below average. METHODS: Nurses implemented medication information labels for patient drinking mugs. Briefing and teach back paired use of the labels with standard medication information sheets. RESULTS: When both mechanisms were used in earnest, HCAHPS unit quarterly scores for medications communication improved from 55% (n=55) to 79% (n=207). Mann-Whitney U confirmed the change was significant (U=4370.0, p=0.001). The change has persisted over three calendar quarters. CONCLUSIONS: Intuitive medications reminders and medication information sheets used in tandem are significantly more effective than when used independently. PMID- 27397823 TI - Patient perceptions and experiences with falls during hospitalization and after discharge. AB - AIMS: The aim of this study was to describe hospitalized older adults' (> 60years) perceptions about (1) their fall risks while hospitalized; (2) fall prevention interventions received while hospitalized; and (3) fall prevention discharge instructions. BACKGROUND: Little is known about hospitalized older adults' perceptions regarding fall prevention interventions received during hospitalization and fall prevention discharge instructions. METHODS: This is a prospective, exploratory study using qualitative methods. RESULTS: This paper reports qualitative findings of patients' perspectives on fall prevention interventions during hospitalization and at discharge. Eight major themes supported by multiple minor themes emerged: overall perceptions of falling; overall perceptions of fall prevention interventions while hospitalized; "telling" fall prevention; "doing" fall prevention; effectiveness of fall prevention strategies; personal fall prevention strategies; fall-related discharge instructions; and most effective fall-related discharge instructions. CONCLUSIONS: Findings suggest healthcare providers need to more fully engage patients and families in understanding fall prevention interventions and factors contributing to falls during hospitalization and at discharge. PMID- 27397824 TI - The Effectiveness of a Nurse-Led Cognitive-Behavioral Therapy on the Quality of Life, Self-Esteem and Mood Among Filipino Patients Living With Heart Failure: a Randomized Controlled Trial. AB - AIMS/OBJECTIVES: The diagnosis and complications associated with heart failure (HF) have been very well established to adversely impact an individual's physical and psychosocial well-being, and interventions such as cognitive-behavioral techniques have demonstrated potential positive benefits among patients with HF. However, the effects of such interventions among Filipino HF patients have not been studied. This study aimed to determine the effectiveness of a nurse-led cognitive-behavioral intervention program on the quality of life, self-esteem and mood among Filipino patients with HF. METHODS: A randomized control two-group design with repeated measures and collected data before and after the intervention was used in this study. Participants were assigned to either the control (n=48) or the intervention group (n=52). Control group participants received traditional care. Intervention participants underwent a 12-week nurse led cognitive-behavioral intervention program focusing on patient education, self monitoring, skills training, cognitive restructuring and spiritual development. Measures of quality of life, self-esteem and mood were obtained at baseline and after the intervention. RESULTS: At baseline, participants in both groups have poor quality of life, low self-esteem, and moderate depressive symptom scores. After the 12-week intervention period, participants in the intervention group had significant improvement in their quality of life, self-esteem and mood scores compared with those who received only standard care. CONCLUSION: Nurse-led cognitive-behavioral intervention is an effective strategy in improving the quality of life, self-esteem and mood among Filipino patients living with HF. It is recommended that this intervention be incorporated in the optimal care of patients with this cardiac condition. PMID- 27397825 TI - A cross-sectional survey of medication adherence and associated factors for rural patients with hypertension. AB - AIM: The objectives of this study were to describe the medication adherence of Chinese rural patients with hypertension and to investigate the factors associated with medication adherence. BACKGROUND: Medication adherence and associated factors for patients with hypertension have been widely explored in previous studies; however, these studies mainly focused on hypertensive patients in urban areas. More information regarding prevalence and the correlated factors for medication adherence for rural patients with hypertension is needed to better control blood pressure and prevent hypertension-related complications. METHODS: The study was carried out in three township hospitals in Shanxi Province (Northern China). A cross-sectional design was adopted to facilitate the survey of rural patients with hypertension. The sample consisted of 1159 participants from three township hospitals. Demographic and clinical characteristic variables, medication adherence and social support were investigated. Multivariate logistic regression was used to test the determinants of adherence. RESULTS: The results demonstrated that 21.3% of patients were adherents to medication and that 78.7% of patients were non-adherents. Most of the participants (71.4%) took medication more than three times daily; only 18.2% of patients took one antihypertensive tablet at a time. Multivariate logistic regression showed that the following variables were associated with medication adherence: age, household income, duration of diagnosis, number of antihypertensive tablets taken in each dose, daily frequency of taking medication, and social support. CONCLUSION: The medication adherence of Chinese rural patients with hypertension is suboptimal. Close attention and effective strategies targeting these patients are necessary; healthcare programs should be designed according to the factors affecting medication adherence. PMID- 27397826 TI - A Meta-Analysis of the Effects of Coping Strategies on Reducing Nurse Burnout. AB - OBJECTIVE: Nurse burnout is a global issue; however, it remains unclear how coping strategies over a maintained period of time may influence nursing burnout. This meta-analysis aimed to evaluate the literature on the effects of coping strategies in reducing nurse burnout. METHODS: Systematic reviews of English and Chinese articles were conducted for relevant articles published between 1979 and 2014 in six electronic databases (PubMed, CINAHL, The Cochrane, PsycARTICLES, Airiti Library, and the Index of the Taiwan Periodical Literature System). The search terms included 'nurse,' 'burnout' and 'coping.' Studies were included in the review if they were randomized controlled trials or controlled clinical trials, and they used the measurement tool, Maslach Burnout Inventory-Human Service Survey. Three hundred fifty-one studies were identified, and seven studies were ultimately included in the meta-analysis. RESULTS: A total of 1,521 participants were included in the meta-analysis for each burnout subgroup. Participants were measured immediately after the intervention and 6months, 1year, 2years, 2.5years, and 4years thereafter. Coping strategies were hypothesized to decrease burnout. The maintained period for coping strategies was 1year for emotional exhaustion and depersonalization and 6months for personal accomplishment. CONCLUSIONS: Coping strategies can reduce nurse burnout and maintain effectiveness between 6months and 1year. PMID- 27397827 TI - Teachers' Influence on Weight Perceptions in Preschool Children. AB - AIM: This study examined the influence of teachers, mothers, and children themselves on weight misperceptions of preschool children. BACKGROUND: Preschool children should have correct perceptions of their weight and develop a positive body image and healthy weight-control behaviors throughout childhood. METHODS: This study used a descriptive cross-sectional design based on the biopsychosocial model. We analyzed 388 triads of Korean children aged 3-6 years, their mothers, and teachers. RESULTS: Children's body mass index (BMI) and weight satisfaction, mothers' BMI; teachers' education level, BMI, perception of and satisfaction with children's weight, body image, and attitude toward obesity were predictors of children underestimating their weight. Mothers' education level and BMI; teachers' BMI, satisfaction with children's weight, and body image were predictors of children overestimating their weight. CONCLUSIONS: Teachers influence weight misperceptions of preschool children. Intervention programs for teachers should incorporate more accurate perceptions of children's weight and promote healthy body image. PMID- 27397829 TI - The Impact of Person-Organization Fit on Nurse Job Satisfaction and Patient Care Quality. AB - PURPOSE: In the current healthcare context, large health care organizations may increasingly emphasize profit, biomedicine, efficiency, and customer service in the delivery of care. This orientation toward nursing work by large organizations may be perceived by nurses as incompatible with professional caring. METHODS: Ordinary Least Squares regression was used to explore the impact of person organization fit (i.e., value congruence between self and employing organization) on nurses' general job satisfaction and quality of patient care (n=753). RESULTS: Nurses' perceived person-organization fit is a significant predictor of general job satisfaction and quality of patient care. CONCLUSION: The implications of our findings are discussed and recommendations for nursing leaders and future research are made. PMID- 27397828 TI - Child and Maternal Factors That Influence Child Blood Pressure in Preschool Children: An Exploratory Study. AB - PURPOSE: Hypertension is a risk factor for cardiovascular disease (CVD) in adults and children and has its origins in childhood. While the prevalence of hypertension in children is estimated to be 2 to 5%, instance elevations in blood pressure readings (BPRs) in school-age children and adolescents are more common, track to adulthood, and are an independent risk factor for CVD. Less information is available about BPR in the preschool period and what child factors could influence those BPR. The primary aims of this exploratory study were to determine child blood pressure (BP) levels and determine effect sizes of the relationships between child and maternal factors that can influence child BP. METHODS: A convenience sample of 15 rural and 15 urban children enrolled in Head Start programs (13 males; 14 females; all black) with ability to understand and speak English and with mothers who gave consent and could understand, read and speak English were enrolled. Mothers completed demographic information about their child including, gender, birth history and age. Height, weight, waist circumference and BP were measured in the mothers and the children. Children gave saliva specimens for cortisol and C-reactive protein. RESULTS: Over 37% of the children had elevated BPR with over 20% at or above the 95th percentile. Effect sizes of relationships ranged from very small to large. CONCLUSION: Elevations in BPR may be seen as early as preschool. It is important to examine factors, both child and maternal that influence BP. PMID- 27397830 TI - A descriptive quantitative study on multi-ethnic patient satisfaction with nursing care measured by the Revised Humane Caring Scale. AB - AIM: To determine patients' satisfaction with nursing care during hospitalization. BACKGROUND: Limited studies reporting patients' satisfaction with quality of nursing care in Singapore. METHOD: A descriptive study was conducted in a tertiary hospital in Singapore. RESULTS: Data were collected from 270 adult patients using the Revised Humane Caring Scale. Patients were moderately satisfied with the nursing care. There were significant differences of patients' level of satisfaction between/among socio-demographic subgroups including ethnicity, gender, reasons for admission and disciplines. Chinese patients were least satisfied with nursing care. The patients were most satisfied with 'Respecting patient's feeling' (mean=82.29, SD=14.50) and least satisfied with 'Communication and participation' (mean=62.00, SD=16.46). CONCLUSION: Our results reinforced the need to pay more attention to patient information provision and effective communication, which could improve patient satisfaction. The multi-ethnic patients valued respect as an influential attribute in quality nursing care. PMID- 27397831 TI - Integrative Review of Nurse-delivered Community-Based Physical Activity Promotion. AB - PURPOSE: The purpose of this integrative review is to 1) describe intervention attributes, 2) describe the role of nurses in community PA promotion, and 3) describe the efficacy of the interventions in terms of PA behavior change. METHODS: Computerized database and ancestry search strategies located distinct intervention trials between 1990 and 2015. RESULTS: Thirteen national and international studies with 2,353 participants were reviewed. Multi-dose, face-to face, group-based interventions with or without individual-based contacts for 6months or less were the most common intervention delivery modes. Only 40% (n=5) of the studies integrated health behavior theory into intervention design. Less than half of the studies demonstrated efficacy in increasing PA. CONCLUSIONS: Results suggest that group-based community interventions, such as exercise classes, group walking and group education/counseling, may be more effective in increasing PA compared to individual-based education. Additional rigorously designed studies are warranted to explore the indicators for successful community based PA promotion. PMID- 27397833 TI - Non-pharmacological and non-surgical treatments for female urinary incontinence: an integrative review. AB - REVIEW AIM: To explore the outcomes of non-pharmacological and non-surgical resources used to treat female urinary incontinence (UI). DESIGN: It is an integrative review (IR) of literature. METHODS: The databases CINAHL, PubMed, PsycINFO, Sociological Abstracts, The Cochrane Library, Scopus, Lilacs, Scielo, IBECS, BDENF, and Medcarib were explored. The grey literature, hand searching, and backtracking of references of primary studies were also explored. The fifteen studies that fulfilled the inclusion criteria were submitted to appraisal of methodological quality and one was excluded, resulting in 14 empirical studies included in this IR. RESULTS: All the treatments, the corresponding instrumental resources, and the support provided by health care providers resulted in the improvement or cure of UI. The pelvic floor muscle training (PFMT) exercise was the main way to treat UI. The multiprofessional involvement, close relationship with patients, continuous monitoring and support associated with PFM training were the factors associated with better adherence to UI treatment and its outcomes. PMID- 27397832 TI - Implementing and Sustaining Evidence Based Practice Through a Nursing Journal Club. AB - BACKGROUND: The outcomes based emphasis in nursing and health care delivery requires identification of best available evidence in order to produce quality, safe, and effective patient care. Finding, critiquing, and ultimately implementing the best available evidence for practice is a formidable task for many clinical nurses. Development and implementation of a nursing journal club (NJC) became one organization's successful attempt to help clinical nurses better understand and use best available evidence in actual practice. METHODS: The process and structure for the NJC evolved from an additional activity scheduled outside of work to a fully established endeavor of Nursing Research and Evidence Based Practice Council (NR&EBP). The Nursing Professional Practice Model was foundational to establishing the NJC as a formal component within the NR&EBP Council shared governance structure. Efforts to embed the NJC included taking advantage of resources available at an academic medical center and incorporating them into the council structure. RESULTS: Successful outcomes of the NJC include a quarterly schedule, with topics selected in advance that are based on nursing department as well as organizational driven goals and initiatives. The structure and process in place has eliminated frequently mentioned deterrents to evidence based practice such as not enough time, lack of knowledge, or no immediate application to practice. CONCLUSIONS: Incorporating the NJC as a component of NR&EBP Council has provided clinical nurses time away from clinical care that supports scholarship for nursing practice. Committed leadership and garnering of available resources have been key factors for success. PMID- 27397834 TI - Intervention for the maintenance and improvement of physical function and quality of life among elderly disaster victims of the Great East Japan Earthquake and Tsunami. AB - PURPOSE: The purpose of this study was to examine the effectiveness of an exercise class implemented in an area affected by the Great East Japan Earthquake and Tsunami for maintaining and improving physical function and quality of life (QOL) among elderly victims. METHODS: Participants were 45 elderly disaster victims. To measure the effectiveness of the exercise classes, results on the Functional Reach Test (FRT), Timed Up and Go Test (TUG), One-leg Standing Balance (OSB), and Chair Stand Test (CST) were measured at the beginning of the exercise classes, and after 3 and 6months. In order to assess health-related QOL, the 8 item Short-Form Health Survey (SF-8) was carried out at the beginning of the exercise classes, and after 1, 3, and 6months. RESULTS: Of the 45 people who consented to participate, 27 continued the program for 6months and were used for analysis. Analysis of the results for FRT, OSB, and CST showed significant improvements (respectively, p=.000, .007, and .000). SF-8 showed significant increases for the subscales of bodily pain (p=.004), general health perception (p=.001), and mental health (p=.035). CONCLUSIONS: By continuing an exercise program for 6months, improvements were seen in lower limb muscle strength and balance functions. Effectiveness for HRQOL was also observed. PMID- 27397836 TI - The effect of family training and support on the quality of life and cost of hospital readmissions in congestive heart failure patients in Iran. AB - BACKGROUND: This study was conducted to investigate the effects of family training and support on quality of life and cost of hospital readmissions in congestive heart failure patients. METHODS: In this single-blinded, randomized, controlled trial, the participants were heart failure patients hospitalized in an Iranian hospital. Data were collected from available hospitalized patients. The participants were enrolled through randomized sampling and were divided randomly into two groups, an intervention group and a control group. The intervention group received extra training package for the disease. Training was provided at discharge and three months after. A standard questionnaire to assess the QoL was filled out by both groups at discharge and six months after. RESULTS: Mean scores of QoL domains at the beginning of the study decreased in control group and increased in intervention in comparison with six months after (p<0.01). CONCLUSION: Nursing care follow-up according to heart failure patients' needs promoted their QoL. PMID- 27397835 TI - Effects of an obesity management mentoring program for Korean children. AB - AIM: This research aimed to develop and test a mentored obesity management program guiding physical exercise, improving eating habits, and promoting self esteem among elementary school learners. METHODS: A nonequivalent control group pretest-posttest design was used. Thirty learners were recruited through convenience sampling from two elementary schools, then evenly assigned to the experimental and control groups. Six nursing students were mentored, receiving 16h of mentorship training. A 10-week mentored obesity management program promoting physical exercise and proper nutrition was developed and provided. RESULTS: The two groups' pretest and posttest body mass index and self-esteem differences were statistically significant. Most participants were satisfied with the program, endorsing its provision in the regular school curriculum. CONCLUSIONS: A mentored obesity management program for elementary school learners would effectively manage weight and improve self-esteem. Programs purportedly curtailing childhood obesity should be expanded, and school policies regulated to enable implementation. PMID- 27397837 TI - Meanings attributed by nurses to ensure the care of critical patients in the light of simulations' premises. AB - AIM: The aim of this study was to identify the feelings experienced by nurses in caring the first visit to a critical patient. BACKGROUND: Understand the ethical aspects from the first experiences in the nursing profession lead us to reflect on the teaching-learning methodologies and also their improvements. METHODS: A study with a mixed and exploratory approach was realized with the nurses. RESULTS: From 72 (100.0%) nurses who participated in the study, 56 (77.8%) did their first visit to critical patients in the clinical practice and did not feel prepared. The feelings mentioned were as follows: insecurity due to lack of skill, risk both to the patient and also the professional, feelings of fear, anxiety, discomfort and related aspects to ethical competence. CONCLUSION: The feelings experienced by professionals led us to reflect about the function of institutions, which must have the commitment and the responsibility of providing to the society able professionals who are acting safely and with technical and scientific expertise in valuing human integrity. PMID- 27397839 TI - Community-based participatory research: Challenges and opportunities. PMID- 27397838 TI - Effectiveness of an education intervention to strengthen nurses' readiness for evidence-based practice: A single-blind randomized controlled study. AB - BACKGROUND: Nurses' lack of readiness for evidence-based practice slows down the uptake, adoption, and implementation of evidence-based practice which is of international concern as it impedes attainment of the highest quality of care and best patient outcomes. There is limited evidence about the most effective approaches to strengthen nurses' readiness for evidence-based practice. OBJECTIVES: To evaluate the effectiveness of an Advanced Practice Nurse-delivered education program to strengthen nurses' readiness for evidence-based practice at a university hospital. DESIGN: A single-blind randomized controlled trial with repeated measures design, with measures completed during spring and fall 2015, before the education program (T0), within 1week after (T1), 8weeks after (T2), and 4months after completion of education interventions (T3). SETTING: One large university hospital system in Finland, consisting of 15 acute care hospitals. PARTICIPANTS: The required sample size, calculated by a priori power analysis and including a 20% estimated attrition rate, called for 85 nurse participants to be recruited. Nurses working in different professional nursing roles and care settings were randomly allocated into two groups: intervention (evidence-based practice education, N=43) and control (research utilization education, N=34). METHODS: The nurse participants received live 4-h education sessions on the basic principles of evidence-based practice (intervention group) and on the principles of research utilization (control group). The intervention group also received a web-based interactive evidence-based practice education module with a booster mentoring intervention. Readiness for evidence-based practice data, previous experience with evidence-based practice, and participant demographics were collected using the Stevens' EBP Readiness Inventory. RESULTS: Nurses' confidence in employing evidence-based practice and actual evidence-based practice knowledge were lower at T0, compared with the post-education scores, specifically at T1. The improvement in the confidence or actual evidence-based practice knowledge levels did not differ between the intervention and control groups. Confidence in employing evidence-based practice was directly correlated with level of education and inversely correlated with age. Actual evidence-based practice knowledge was lowest among nurses who had no previous knowledge or experience of evidence-based practice. CONCLUSIONS: Both the evidence-based practice and research utilization education interventions improved nurses' confidence in employing evidence-based practice and actual evidence-based practice knowledge, strengthening their evidence-based practice readiness at least in the short-term. Most of the variation in the confidence in employing evidence-based practice and actual evidence-based practice knowledge levels was due to background factors, such as primary role and education level, which emphasize differences in educational needs between nurses with diverse backgrounds. PMID- 27397840 TI - Influence of ozonation and biodegradation on toxicity of industrial textile wastewater. AB - The textile industry demands huge volumes of high quality water which converts into wastewater contaminated by wide spectrum of chemicals. Estimation of textile wastewater influence on the aquatic systems is a very important issue. Therefore, closing of the water cycle within the factories is a promising method of decreasing its environmental impact as well as operational costs. Taking both reasons into account, the aim of this work was to establish the acute toxicity of the textile wastewater before and after separate chemical, biological as well as combined chemical-biological treatment. For the first time the effects of three different combinations of chemical and biological methods were investigated. The acute toxicity analysis were evaluated using the Microtox(r) toxicity test. Ozonation in two reactors of working volume 1 dm3 (stirred cell) and 20 dm3 (bubble column) were tested as chemical process, while biodegradation was conducted in two, different systems - Sequence Batch Reactors (SBR; working volume 1.5 dm3) and Horizontal Continuous Flow Bioreactor (HCFB; working volume 12 dm3). The untreated wastewater had the highest toxicity (EC50 value in range: 3-6%). Ozonation caused lower reduction of the toxicity than biodegradation. In the system with SBR the best results were obtained for the biodegradation followed by the ozonation and additional biodegradation - 96% of the toxicity removal. In the second system (with HCFB) two-stage treatment (biodegradation followed by the ozonation) led to the highest toxicity reduction (98%). PMID- 27397841 TI - Assessing the effectiveness of a three-stage on-farm biobed in treating pesticide contaminated wastewater. AB - Agricultural point source pesticide pollution arising from contaminated machinery washings and accidental spillages pose a significant threat to river water and groundwater quality. In this study, we assess the effectiveness of a three-stage on-farm biobed for treating pesticide contaminated wastewater from a large (20 km(2)) commercial arable estate. The facility consisted of an enclosed machinery wash-down unit (stage 1), a 49 m(2) lined compost-straw-topsoil biobed (stage 2), and a 200 m(2) drainage field with a trickle irrigation system (stage 3). Pesticide concentrations were analysed in water samples collected fortnightly between November 2013 and November 2015 from the biobed input and output sumps and from 20 porous pots buried at 45 cm and 90 cm depth within the drainage field. The results revealed that the biobed removed 68-98% of individual pesticides within the contaminated washings, with mean total pesticide concentrations reducing by 91.6% between the biobed input and output sumps. Drainage field irrigation removed a further 68-99% of individual pesticides, with total mean pesticide concentrations reducing by 98.4% and 97.2% in the 45 cm and 90 cm depth porous pots, respectively. The average total pesticide concentration at 45 cm depth in the drainage field (57 MUg L(-1)) was 760 times lower than the mean concentration recorded in the input sump (43,334 MUg L(-1)). There was no evidence of seasonality in the efficiency of biobed pesticide removal, nor was there evidence of a decline in removal efficiency over the two-year monitoring period. However, higher mean total pesticide concentrations at 90 cm (102 MUg L( 1)) relative to 45 cm (57 MUg L(-1)) depth indicated an accumulation of pesticide residues deeper within the soil profile. Overall, the results presented here demonstrate that a three-stage biobed can successfully reduce pesticide pollution risk from contaminated machinery washings on a commercial farm. PMID- 27397842 TI - Synthesis, characterization and performance of high energy ball milled meso-scale zero valent iron in Fenton reaction. AB - Understanding contaminant degradation by different sized zero valent iron (ZVI) particles is one important aspect in addressing the long-term stability of these particles in field studies. In this study, meso zero valent iron (mZVI) particles were synthesised in a milling time of 10 h using ball milling technique. The efficacy of mZVI particles for removal of phenol was quantitatively evaluated in comparison with coarse zero valent iron (cZVI) and nano zero valent iron (nZVI) particles. Phenol degradation experiments were carried out in sacrificial batch mode at room temperature independently with cZVI, nZVI and mZVI under varied pH conditions of 3, 4, 6, 7, 8 and 10. Batch experiments substantiating the reactivity of mZVI under unbuffered pH system were also carried out and compared with buffered and poorly buffered pH systems. mZVI particles showed consistent phenol degradation at circum-neutral pH with efficiency of 44%, 67%, and 89% in a span of 5, 10 and 20 min respectively. The dissolved iron species and residual iron formation were also measured as a function of pH. Unbuffered systems at circum-neutral pH produced less residual iron when compared to buffered and poorly buffered systems. At this pH, oxidation of Fe(2+) produced a different oxidant Ferryl ion, which was found to effectively participate in phenol degradation. PMID- 27397843 TI - Concretes and mortars with waste paper industry: Biomass ash and dregs. AB - This article describes a study on the viability of using waste from the paper industry: biomass boiler ash and green liquor dregs to fabricate mortars and concretes. Both types of ash were characterized by obtaining their chemical and mineralogical composition, their organic matter content, granulometry, adsorption and other common tests for construction materials. Seven different mortars were fabricated, one for reference made up of cement, sand, and water, three in which 10, 20, or 30% of the cement was replaced by biomass ash, and three others in which 10, 20, or 30% of the cement was replaced with dregs. Test specimens were fabricated with these mortars to conduct flexural and compression tests. Flexural strength is reduced for all the mortars studied. Compressive strength increases for the mortars fabricated with biomass ash and decreases for the mortar with dregs. Finally, 5 concretes were made, one of them as a reference (neither biomass ash nor dregs added), two of them with replacements of 10 and 20% of biomass ash instead of cement and another two with replacements of 10 and 20% of dregs instead of cement. The compressive and tensile splitting strength increase when a 10% of ash is replaced and decrease in all the other cases. The modulus of elasticity always decreases. PMID- 27397844 TI - Potential use of algae for heavy metal bioremediation, a critical review. AB - Algae have several industrial applications that can lower the cost of biofuel co production. Among these co-production applications, environmental and wastewater bioremediation are increasingly important. Heavy metal pollution and its implications for public health and the environment have led to increased interest in developing environmental biotechnology approaches. We review the potential for algal biosorption and/or neutralization of the toxic effects of heavy metal ions, primarily focusing on their cellular structure, pretreatment, modification, as well as potential application of genetic engineering in biosorption performance. We evaluate pretreatment, immobilization, and factors affecting biosorption capacity, such as initial metal ion concentration, biomass concentration, initial pH, time, temperature, and interference of multi metal ions and introduce molecular tools to develop engineered algal strains with higher biosorption capacity and selectivity. We conclude that consideration of these parameters can lead to the development of low-cost micro and macroalgae cultivation with high bioremediation potential. PMID- 27397845 TI - The removal of sulphate from mine water by precipitation as ettringite and the utilisation of the precipitate as a sorbent for arsenate removal. AB - The aim of this research was to investigate sulphate removal from mine water by precipitation as ettringite (Ca6Al2(SO4)3(OH)12.26H2O) and the utilisation of the precipitate as a sorbent for arsenate removal. The mine water sulphate concentration was reduced by 85-90% from the initial 1400 mg/L during ettringite precipitation depending on the treatment method. The precipitation conditions were also simulated with MINEQL + software, and the computational results were compared with the experimental results. The precipitated solids were characterised with X-ray diffraction and a scanning electron microscope. The precipitated solids were tested as sorbents for arsenate removal from the model solution. The arsenic(V) model solution concentration reduced 86-96% from the initial 1.5 mg/L with a 1 g/L sorbent dosage. The effect of initial arsenate concentration on the sorption of arsenate on the precipitate was studied and Langmuir, Freundlich, and Langmuir-Freundlich sorption isotherm models were fitted to the experimental data. The maximum arsenate sorption capacity (qm = 11.2 +/- 4.7 mg/g) of the precipitate was obtained from the Langmuir-Freundlich isotherm. The results indicate that the precipitate produced during sulphate removal from mine water by precipitation as ettringite could be further used as a sorbent for arsenate removal. PMID- 27397846 TI - Combined systemic elimination of MET and epidermal growth factor receptor signaling completely abolishes liver regeneration and leads to liver decompensation. AB - : Receptor tyrosine kinases MET and epidermal growth factor receptor (EGFR) are critically involved in initiation of liver regeneration. Other cytokines and signaling molecules also participate in the early part of the process. Regeneration employs effective redundancy schemes to compensate for the missing signals. Elimination of any single extracellular signaling pathway only delays but does not abolish the process. Our present study, however, shows that combined systemic elimination of MET and EGFR signaling (MET knockout + EGFR-inhibited mice) abolishes liver regeneration, prevents restoration of liver mass, and leads to liver decompensation. MET knockout or simply EGFR-inhibited mice had distinct and signaling-specific alterations in Ser/Thr phosphorylation of mammalian target of rapamycin, AKT, extracellular signal-regulated kinases 1/2, phosphatase and tensin homolog, adenosine monophosphate-activated protein kinase alpha, etc. In the combined MET and EGFR signaling elimination of MET knockout + EGFR-inhibited mice, however, alterations dependent on either MET or EGFR combined to create shutdown of many programs vital to hepatocytes. These included decrease in expression of enzymes related to fatty acid metabolism, urea cycle, cell replication, and mitochondrial functions and increase in expression of glycolysis enzymes. There was, however, increased expression of genes of plasma proteins. Hepatocyte average volume decreased to 35% of control, with a proportional decrease in the dimensions of the hepatic lobules. Mice died at 15-18 days after hepatectomy with ascites, increased plasma ammonia, and very small livers. CONCLUSION: MET and EGFR separately control many nonoverlapping signaling endpoints, allowing for compensation when only one of the signals is blocked, though the combined elimination of the signals is not tolerated; the results provide critical new information on interactive MET and EGFR signaling and the contribution of their combined absence to regeneration arrest and liver decompensation. (Hepatology 2016;64:1711-1724). PMID- 27397848 TI - Rapsyn congenital myasthenic syndrome worsened by fluoxetine. AB - INTRODUCTION: Fluoxetine is a selective serotonin reuptake inhibitor and long lived open channel blocker of the acetylcholine receptor, often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). METHODS: We report a 42-year-old woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed before and 1 month after discontinuation of fluoxetine. RESULTS: The 2 Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. CONCLUSIONS: This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. Muscle Nerve 55: 131-135, 2017. PMID- 27397847 TI - Neural correlates of impaired self-awareness of apathy, disinhibition and dysexecutive deficits in cocaine-dependent individuals. AB - Cocaine addiction is characterized by impaired self-awareness about cognitive and motivational deficits, leading to poor treatment outcomes. However, there is still limited understanding of the neurophysiological underpinnings of this impairment. We aimed to establish if impaired self-awareness is underpinned by brain structural phenotypes among cocaine-dependent individuals (CDI). Sixty-five CDI and 65 designated informants completed the Frontal Systems Behavior Scale, and a subsample of 40 CDI were scanned via magnetic resonance imaging. We applied multiple regression models to establish the association between levels of self awareness indexed by Frontal Systems Behavior Scale's discrepancy scores (i.e. informant ratings minus self-reports of apathy, disinhibition and dysexecutive deficits) and gray matter volumes indexed by magnetic resonance imaging voxel based measures within five brain regions of interest: anterior cingulate cortex, orbitofrontal cortex (OFC), striatum, insula and dorsolateral prefrontal cortex (DLPFC). We also examined the neural underpinnings of underestimation versus overestimation of deficits, by splitting the CDI group according to the positive or negative value of their discrepancy scores. We found that poorer self awareness of apathy deficits was associated with greater gray matter volume in the dorsal striatum, and poorer self-awareness of disinhibition deficits was associated with greater gray matter volume in the OFC in the whole sample. More underestimation and more overestimation of executive deficits were linked to lower DLPFC volume. We show that impaired self-awareness of cognitive and motivational deficits in cocaine addiction has a neural underpinning, implicating striatum, OFC and DLPFC structural phenotypes. PMID- 27397849 TI - Biweekly Carboplatin Plus Gemcitabine as First-Line Treatment of Elderly Patients With Advanced Squamous Non-Small-cell Lung Cancer: A Multicenter Phase I-II Trial by the Hellenic Oncology Research Group. AB - BACKGROUND: The present study was a phase I/II study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities of the biweekly carboplatin/gemcitabine combination and evaluate its safety and efficacy in patients aged >= 70 years with advanced squamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged >= 70 years with advanced or metastatic squamous NSCLC received escalated doses of carboplatin (area under the curve [AUC] 2-2.5 intravenously) and gemcitabine (800-1100 mg/m2 intravenously) every 2 weeks (phase I). In the phase II, the drugs were administered at their previously defined MTDs (carboplatin, AUC 2.5; gemcitabine, 1100 mg/m2). The primary endpoint was the overall response rate. RESULTS: A total of 69 patients were enrolled (phase I, n = 15). The median age was 76 years (range, 70-84 years); 52 patients had stage IV disease, and 61 and 8 patients had Eastern Cooperative Oncology Group performance status of 0 to 1 and 2, respectively. The MTDs could not be reached at the predefined last dose levels. The dose-limiting toxicities were grade 5 renal toxicity and grade 3 thrombocytopenia. In the phase II study, the overall response rate was 35.8% (95% confidence interval [CI], 23.0%-48.8%). In the intention-to-treat analysis, the median progression-free survival was 6.7 months (95% CI, 4.2-8.8 months), and the median overall survival was 13.3 months (95% CI, 7.1-19.6 months). Grade 3 or 4 neutropenia was observed in 7 patients (12.3%), grade 3 or 4 thrombocytopenia in 4 patients (7.1%), and grade 2 or 3 fatigue in 10 patients (17.5%). One toxic death occurred in the phase I of the study. CONCLUSION: The biweekly regimen of gemcitabine and carboplatin showed satisfactory efficacy and a favorable toxicity profile in elderly patients with advanced or metastatic squamous cell NSCLC. PMID- 27397850 TI - Cost-effectiveness of regular versus irregular supportive periodontal therapy or tooth removal. AB - AIM: For periodontitis patients, regular supportive periodontal therapy (SPT) decreases risks of tooth loss, with savings for tooth replacement possibly compensating SPT-costs. We aimed to assess the cost-effectiveness of regular versus irregular SPT, and to compare both strategies with immediate tooth removal. METHODS: A private payer perspective within German healthcare was adopted. A tooth-level Markov model was constructed. Replacement of 50% of removed teeth via implant-supported crowns was modelled in the base case. Cost effectiveness was estimated as Euro/tooth retention year using Monte Carlo microsimulations. Scenario analyses were performed. RESULTS: Regular SPT was more effective (tooth retention 28.7 versus 26.1 years), but more costly (806 versus 731 Euro per tooth), with an incremental cost-effectiveness ratio (additional costs per tooth retention year) of 29 Euro/year. Regular SPT was less costly if costs for SPT per tooth and visit were <5.03 Euro, patients had high risk of tooth loss, or teeth were regularly replaced. Immediately removing and replacing teeth was usually most costly. CONCLUSIONS: Within the chosen healthcare setting and on the basis of current evidence, regular SPT retains teeth longer than irregular SPT, but does not necessarily reduce expenses. Decision-making should consider the subjective value placed on retaining teeth, the technical feasibility of replacement, and the impact of periodontal on general health. PMID- 27397851 TI - Chlamydia-host cell interaction not only from a bird's eye view: some lessons from Chlamydia psittaci. AB - Chlamydia psittaci causes psittacosis/ornithosis in birds and is an economically important pathogen for poultry farming. It also infects nonavian domestic animals as well as rodents, and is a zoonotic human pathogen responsible for atypical pneumonia. The bacterium efficiently disseminates in host organisms causing pulmonary and systemic disease. Its rapid entry, fast replication cycle, and tight control of intracellular transport routes contribute to the host-to-host transmission and efficient growth observed with C. psittaci. Recent studies have revealed that the pathogen copes better than other chlamydial strains with proinflammatory effectors produced during the early immune reaction of infected hosts. These features likely contribute to successful infections and might explain the potent adaptation and evasion characteristics of the agent. Current findings on cell-autonomous, innate, and adaptive defenses against C. psittaci provide novel insights into the concerted immune mechanisms involved in the clearance of the pathogen. Further in-depth studies on C. psittaci and other related agents in cellular as well as animal models are needed to develop more efficient antichlamydial therapies and vaccination strategies. PMID- 27397852 TI - Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression. AB - Distant organ metastasis of prostate cancer is a puzzle, and various theories have successively arisen to explain the mechanism of lethal cancer progression. While perhaps agreeable to many cancer biologists, the very statement of "seed and soil" proposed by Stephan Paget in 1881 is arguably still the major statement for organ-specific cancer metastasis. Since recent studies showed important correlations of regulation of cancer cells and the microenvironment, exosomes from cancer and stromal cells seem to create another important niche for metastasis. Stromal cells pretreated with exosomes from metastatic cancer cells increase the potential of change stromal cells. The poorly metastatic cancer cells could also enhance malignancy through transfer of proteins, microribonucleic acid and messenger ribonucleic acid to recipient cancer cells. Herein, we reviewed extracellular exosomes as a factor involved in cross-talk between stromal and prostate cancer epithelial cells. PMID- 27397854 TI - Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases. AB - Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population. PMID- 27397853 TI - The 5-amino acid N-terminal extension of non-sulfated drosulfakinin II is a unique target to generate novel agonists. AB - The ability to design agonists that target peptide signaling is a strategy to delineate underlying mechanisms and influence biology. A sequence that uniquely characterizes a peptide provides a distinct site to generate novel agonists. Drosophila melanogaster sulfakinin encodes non-sulfated drosulfakinin I (nsDSK I; FDDYGHMRF-NH2) and nsDSK II (GGDDQFDDYGHMRF-NH2). Drosulfakinin is typical of sulfakinin precursors, which are conserved throughout invertebrates. Non-sulfated DSK II is structurally related to DSK I, however, it contains a unique 5-residue N-terminal extension; drosulfakinins signal through G-protein coupled receptors, DSK-R1 and DSK-R2. Drosulfakinin II distinctly influences adult and larval gut motility and larval locomotion; yet, its structure-activity relationship was unreported. We hypothesized substitution of an N-terminal extension residue may alter nsDSK II activity. By targeting the extension we identified, not unexpectedly, analogs mimicking nsDSK II, yet, surprisingly, we also discovered novel agonists with increased (super) and opposite (protean) effects. We determined [A3] nsDSK II increased larval gut contractility rather than, like nsDSK II, decrease it. [N4] nsDSK II impacted larval locomotion, although nsDSK II was inactive. In adult gut, [A1] nsDSK II, [A2] nsDSKII, and [A3] nsDSK II mimicked nsDSK II, and [A4] nsDSK II and [A5] nsDSK II were more potent; [N3] nsDSK II and [N4] nsDSK II mimicked nsDSK II. This study reports nsDSK II signals through DSK-R2 to influence gut motility and locomotion, identifying a novel role for the N-terminal extension in sulfakinin biology and receptor activation; it also led to the discovery of nsDSK II structural analogs that act as super and protean agonists. PMID- 27397855 TI - MRI rectal cancer in Australia and New Zealand: An audit from the PETACC-6 trial. AB - INTRODUCTION: An MRI audit substudy was conducted in patients who underwent an MRI prior to treatment in Australia and New Zealand as part of the PETACC-6 trial in locally advanced rectal cancer. METHODS: A total of 82 patients from 15 centres had rectal MRI scans reviewed for technique, data included in reports and comparison of reports with blinded central reporting by two experienced radiologists. RESULTS: In total, 82% performed minimum T2 sagittal and T2 axial oblique sequences. The high-resolution T2 sequence parameters varied significantly with only 33% obtaining a voxel size of <1.3 mm3 . The rate of inclusion of relevant findings in the reports was T3 distance in mm 21%, N stage 84%, circumferential resection margin (CRM) status 72%, extramural venous invasion (EMVI) status 29% and distance from the puborectalis sling 17%. In total, 31% reports included all of T stage with T3 substage, N stage and CRM involvement. In total, 17% reports included these 3 findings and EMVI. Eleven reports used a template with 82% of these including the first 3 findings. The agreement with central reporters was T stage 76%, N stage 70%, CRM status 57% and EMVI 16%. CONCLUSION: There is significant variation in scan quality and low rates of including all relevant findings in rectal MRI reports in the audit. The authors recommend adoption of routine sequences and template reports in both trial settings and routine practice to improve scan technique and adequacy of reports in rectal cancer MRI staging scans across Australia and New Zealand. PMID- 27397856 TI - ATR-IR Investigation of Solvent Interactions with Surface-Bound Polymers. AB - Solvent interactions with bulk and surface-bound polymer brushes are crucial for functionalities such as controlled friction and thermoresponsive adhesion. To study such interactions, the temperature-induced solvent-quality changes and the effect of surface tethering on the mechanical and tribological properties of poly(dodecyl methacrylate) (P12MA) brushes have been investigated by means of attenuated total reflection infrared spectroscopy (ATR-IR), as well as atomic force microscopy (AFM) and lateral force microscopy (LFM). These results have been compared with temperature-dependent UV-visible spectrophotometry (UV-vis) data for the corresponding bulk polymer solutions. The ATR-IR results clearly show that increasing temperature enhances ethanol uptake in P12MA, which results in film swelling. This is accompanied by a marked increase in both adhesion and friction. We have also shown that a combination of solvents, such as toluene and ethanol, can lead to a temperature-dependent solvent partitioning within the polymer brush. To our knowledge this is the first time preferential solvent uptake in a grafted-from brush has been monitored via in situ ATR-IR. Moreover, we have observed remarkably different behavior for polymer chains in solution compared to the behavior of similar chains bound to a surface. The presented findings on the temperature-dependent solvent interactions of surface-grafted P12MA reveal previously unknown solvation phenomena and open up a range of possible applications in the area of stimuli-responsive materials. PMID- 27397857 TI - A Conceptual Model for Episodes of Acute, Unscheduled Care. AB - We engaged in a 1-year process to develop a conceptual model representing an episode of acute, unscheduled care. Acute, unscheduled care includes acute illnesses (eg, nausea and vomiting), injuries, or exacerbations of chronic conditions (eg, worsening dyspnea in congestive heart failure) and is delivered in emergency departments, urgent care centers, and physicians' offices, as well as through telemedicine. We began with a literature search to define an acute episode of care and to identify existing conceptual models used in health care. In accordance with this information, we then drafted a preliminary conceptual model and collected stakeholder feedback, using online focus groups and concept mapping. Two technical expert panels reviewed the draft model, examined the stakeholder feedback, and discussed ways the model could be improved. After integrating the experts' comments, we solicited public comment on the model and made final revisions. The final conceptual model includes social and individual determinants of health that influence the incidence of acute illness and injury, factors that affect care-seeking decisions, specific delivery settings where acute care is provided, and outcomes and costs associated with the acute care system. We end with recommendations for how researchers, policymakers, payers, patients, and providers can use the model to identify and prioritize ways to improve acute care delivery. PMID- 27397858 TI - Derivatization Strategy for the Comprehensive Characterization of Endogenous Fatty Aldehydes Using HPLC-Multiple Reaction Monitoring. AB - Fatty aldehydes are crucial substances that mediate a wide range of vital physiological functions, particularly lipid peroxidation. Fatty aldehydes such as acrolein and 4-hydroxynonenal (4-HNE) are considered potential biomarkers of myocardial ischemia and dementia, but analytical techniques for fatty aldehydes are lacking. In the present study, a comprehensive characterization strategy with high sensitivity and facility for fatty aldehydes based on derivatization and high-performance liquid chromatography-multiple reaction monitoring (HPLC-MRM) was developed. The fatty aldehydes of a biosample were derivatized using 2,4 bis(diethylamino)-6-hydrazino-1,3,5-triazine under mild and efficient reaction conditions at 37 degrees C for 15 min. The limit of detection (LOD) of the fatty aldehydes varied from 0.1 to 1 pg/mL, depending on the structures of these molecules. General MRM parameters were forged for the analysis of endogenous fatty aldehydes. "Heavy" derivatization reagents with 20 deuterium atoms were synthesized for both the discovery and comprehensive characterization of fatty aldehydes. More than 80 fatty aldehydes were detected in the biosamples. The new strategy was successfully implemented in global fatty aldehyde profiling of plasma and brain tissue of the bilateral common carotid artery (2VO) dementia rat model. Dozens of fatty aldehydes were significantly changed between the control and model groups. These findings further highlight the importance of endogenous fatty aldehydes. PMID- 27397859 TI - CASE 13-2016 Minimally Invasive Left Ventricular Assist Device Insertion Without Cardiopulmonary Bypass. PMID- 27397860 TI - The Valve Behind the Curtain. PMID- 27397861 TI - Left Ventricular Outflow Tract Area Measurements by Planimetry Using Two Dimensional Simultaneous Orthogonal Plane Imaging During Transesophageal Echocardiography. AB - OBJECTIVE: Calculations of the left ventricular outflow tract (LVOT) area are typically based on the assumption that the LVOT is circular. This study was conducted to determine whether simultaneous orthogonal plane imaging with tilt during two-dimensional (2D) transesophageal echocardiography provided more accurate measurements of the LVOT area than the standard method. DESIGN: The authors prospectively measured the LVOT area in 2D by (1) the standard calculation based on the diameter as viewed on the long axis, and (2) a direct measurement using planimetry of the short axis, in consecutive patients presenting for elective surgery. The authors validated the planimetric technique by obtaining three-dimensional (3D) measurements in a subset of the subjects. SETTING: An academic medical center. PARTICIPANTS: Adult surgical patients with no evidence of aortic stenosis. INTERVENTIONS: Transesophageal images were acquired by anesthesiologists certified by the National Board of Echocardiography. MEASUREMENTS AND MAIN RESULTS: Image acquisition and assessment were performed in the operating room and found to be adequate for analysis in 52 of 55 subjects. Simultaneous orthogonal plane imaging with tilt enabled long- and short-axis visualization of the LVOT. The authors found that the standard method underestimated the area by 0.78 cm(2) compared to the direct method (2D planimetry) when measured at the same beat at a similar point in the cardiac cycle. Moreover, 2D planimetry measurements were comparable to 3D planimetry measurements in the last 20 study subjects (R(2) = 0.88, p<0.0001). CONCLUSIONS: This study suggested that 2D planimetry may be more accurate than 2D diameter based calculations. PMID- 27397862 TI - Knockdown of corticotropin-releasing factor 1 receptors in the ventral tegmental area enhances conditioned fear. AB - The neuropeptide corticotropin-releasing factor (CRF) coordinates the physiological and behavioural responses to stress. CRF receptors are highly expressed in the ventral tegmental area (VTA), an important region for motivated behaviour. Therefore, we examined the role of CRF receptor type 1 (CRFR1) in the VTA in conditioned fear, using a viral-mediated RNA interference approach. Following stereotaxic injection of a lentivirus that contained either shCRF-R1 or a control sequence, mice received tone-footshock pairings. Intra-VTA shCRF-R1 did not affect tone-elicited freezing during conditioning. Once conditioned fear was acquired, however, shCRF-R1 mice consistently showed stronger freezing to the tone even after extinction and reinstatement. These results implicate a novel role of VTA CRF-R1 in conditioned fear, and suggest how stress may modulate aversive learning and memory. PMID- 27397863 TI - Largely overlapping neuronal substrates of reactivity to drug, gambling, food and sexual cues: A comprehensive meta-analysis. AB - Cue reactivity to natural and social rewards is essential for motivational behavior. However, cue reactivity to drug rewards can also elicit craving in addicted subjects. The degree to which drug and natural rewards share neural substrates is not known. The objective of this study is to conduct a comprehensive meta-analysis of neuroimaging studies on drug, gambling and natural stimuli (food and sex) to identify the common and distinct neural substrates of cue reactivity to drug and natural rewards. Neural cue reactivity studies were selected for the meta-analysis by means of activation likelihood estimations, followed by sensitivity and clustering analyses of averaged neuronal response patterns. Data from 176 studies (5573 individuals) suggests largely overlapping neural response patterns towards all tested reward modalities. Common cue reactivity to natural and drug rewards was expressed by bilateral neural responses within anterior cingulate gyrus, insula, caudate head, inferior frontal gyrus, middle frontal gyrus and cerebellum. However, drug cues also generated distinct activation patterns in medial frontal gyrus, middle temporal gyrus, posterior cingulate gyrus, caudate body and putamen. Natural (sexual) reward cues induced unique activation of the pulvinar in thalamus. Neural substrates of cue reactivity to alcohol, drugs of abuse, food, sex and gambling are largely overlapping and comprise a network that processes reward, emotional responses and habit formation. This suggests that cue-mediated craving involves mechanisms that are not exclusive for addictive disorders but rather resemble the intersection of information pathways for processing reward, emotional responses, non-declarative memory and obsessive-compulsive behavior. PMID- 27397864 TI - Glucocorticoid receptor gene modulates severity of depression in women with crack cocaine addiction. AB - Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit higher rates of depressive symptoms. There is strong evidence that the identification of genetic variants in depression is potentialized when reducing phenotypic heterogeneity by studying selected groups. Since depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis, this study evaluated the effects of SNPs in stress-related genes on depressive symptoms of crack cocaine addicts at early abstinence and over the detoxification treatment (4th, 11th and 18th day post admission). Also, the role of these SNPs on the re-hospitalization rates after 2.5 years of follow-up was studied. One hundred eight-two women were enrolled and eight SNPs in four genes (NR3C2, NR3C1, FKBP5 and CRHR1) were genotyped. A significant main effect of NR3C1-rs41423247 was found, where the C minor allele increased depressive symptoms at early abstinence. This effect remained significant after 10,000 permutations to account for multiple SNPs tested (P=0.0077). There was no effect of rs41423247 on the course of detoxification treatment, but a slight effect of rs41423247 at late abstinence was detected (P=0.0463). This analysis suggests that the presence of at least one C allele is worse at early abstinence, while only CC genotype appears to increase depressive symptoms at late abstinence. Also, a slight effect of rs41423247 C minor allele increasing the number of re-hospitalizations after 2.5 years was found (P=0.0413). These findings are in agreement with previous studies reporting an influence of rs41423247 on sensitivity to glucocorticoids and further elucidate its resulting effects on depressive-related traits. PMID- 27397865 TI - GATA4 variant interaction with brain limbic structure and relapse risk: A voxel based morphometry study. AB - Atrial natriuretic peptide (ANP) receptors are highly expressed in the amygdala, caudate and hypothalamus. GATA4 gene encodes a transcription factor of ANP associated with the pathophysiology of alcohol dependence. We have previously demonstrated that the GATA4 single nucleotide polymorphism (SNP) rs13273672 revealed stronger alcohol-specific amygdala activation associated with lowered relapse risk to heavy drinking at 90 days in the AA-homozygotes. Our understanding however with respect to GATA4 variation on gray matter (GM) regional amygdala, caudate and hypothalamus volume is limited. We investigated GM differences specific to GATA4 and hypothesized that GM alterations will be predictive of heavy relapse. Eighty-three recently detoxified alcohol dependent patients were included. Neuroimaging data was analyzed using Voxel Based Morphometry (VBM). The main effects of GM volume and genotype as well as their interaction effect on time to heavy relapse (60 and 90 days) were analyzed using cox regression. Significant higher GM volume was found for the AA-genotype group compared with AG/GG-genotype in the hypothalamus and caudate. A significant interaction was revealed between caudate and amygdala GM volume and GATA4 genotype on time to heavy relapse. The interaction was expressed by means of higher GM in the AA genotype group to be associated with reduced risk to relapse whereas in the AG/GG group higher GM was associated with increased risk to relapse. This is the first report on GM regional volume alterations specific to GATA4 genotype [(SNP) rs13273672] and its association with relapse in alcohol dependence. Current findings further support the role of GATA4 in alcoholism. PMID- 27397866 TI - Radiographic localisation of the entheses of the equine stifle. AB - REASON FOR PERFORMING STUDY: Injury to the tendons and ligaments of the equine stifle is a common cause of lameness in horses. Individual radiographic localisation of each tendon and ligament of the stifle has not been previously reported or demonstrated in multiple radiographic projections. OBJECTIVE: To create a series of radiographs identifying the origins and/or insertions of the tendons and ligaments of the equine stifle. STUDY DESIGN: Descriptive study of radiographic anatomy. METHODS: The location of all entheses were determined by gross dissection. The proximal tibia and fibula, distal femur, patella and menisci were isolated from one horse and used as a template. A series of 4 radiographs was obtained with each enthesis identified with barium paste. The radiographic landmarks for each enthesis were described and the best projection(s) for evaluation of each structure of interest identified. RESULTS: Forty-eight radiographic images were produced that demonstrated the best radiographic projections to define each enthesis. CONCLUSIONS: Radiography is the imaging modality most frequently used to evaluate the equine stifle. The images presented here will serve as a guide for evaluating radiographs of the equine stifle, particularly identifying avulsions and enthesopathies of ligamentous and tendinous origins and insertions. PMID- 27397867 TI - Referral of young children to dental personnel by primary care nurses. AB - : Oral health promotion to young children is delivered by primary care nurses as part of general health promotion given to all children in Norway. OBJECTIVE: The objective was to evaluate established routines for referral of children by primary care nurses to the dental services and to study whether referred children younger than 3 years required contact with dental personnel. METHODS: All children referred by primary care nurses to the dental services in one county during one year were included. Primary care nurses referred children using criteria developed by dental personnel. At the dental clinic, anamnestic information, dental health and oral health behaviour of the referred children were registered. RESULTS: Altogether, 181 children were referred; 53% were younger than 3 years. The most frequent reasons for referral of children younger than 3 years were caries or dental plaque, and 34% had visible plaque accumulation and/or visible signs of caries. All referred children had at least one risk factor for caries. The referral reasons given by primary care nurses corresponded partly with findings at dental examination. The results indicated that 2% of the children younger than 3 years were referred to the dental services. CONCLUSION: The results indicated that by using established referral routines, all children referred from well-baby clinics to the dental services were caries risk children who required early contact with dental personnel. However, the low proportion of children in the studied population referred by primary care personnel may indicate under-referral of children to the dental services. PMID- 27397868 TI - Comparison of solvent-wetted and kneaded l-sulpiride-loaded solid dispersions: Powder characterization and in vivo evaluation. AB - The purpose of this study was to compare the powder properties, solubility, dissolution and oral absorption of solvent-wetted (SWSD) and kneaded (KNSD) l sulpiride-loaded solid dispersions. The SWSD and KNSD were prepared with silicon dioxide, sodium laurylsulfate and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) using a spray dryer and high shear mixer, respectively. Their powder properties, solubility, dissolution and oral absorption were assessed compared to l-sulpiride powder. The drug in SWSD was in the amorphous state; however, in KNSD, it existed in the crystalline state. The SWSD with a drug/sodium laurylsulphate/TPGS/silicon dioxide ratio of 5/1/2/12 gave the higher drug solubility and dissolution compared to the KNSD with the same composition. The oral absorption of drug in the SWSD was 1.4 fold higher than the KNSD and 3.0 fold higher than the l-sulpiride powder (p<0.05) owing to better solubility and reduced crystallinity. Furthermore, the SWSD at the half dose was bioequivalent of commercial l-sulpiride-loaded product in rats. Thus, the SWSD with more improved oral absorption would be recommended as an alternative for the l sulpiride-loaded oral administration. PMID- 27397869 TI - Considerations on the quantitative analysis of apparent amorphicity of milled lactose by Raman spectroscopy. AB - The main purpose of the study was to evaluate various pre-processing and quantification approaches of Raman spectrum to quantify low level of amorphous content in milled lactose powder. To improve the quantification analysis, several spectral pre-processing methods were used to adjust background effects. The effects of spectral noise on the variation of determined amorphous content were also investigated theoretically by propagation of error analysis and were compared to the experimentally obtained values. Additionally, the applicability of calibration method with crystalline or amorphous domains in the estimation of amorphous content in milled lactose powder was discussed. Two straight baseline pre-processing methods gave the best and almost equal performance. By the succeeding quantification methods, PCA performed best, although the classical least square analysis (CLS) gave comparable results, while peak parameter analysis displayed to be inferior. The standard deviations of experimental determined percentage amorphous content were 0.94% and 0.25% for pure crystalline and pure amorphous samples respectively, which was very close to the standard deviation values from propagated spectral noise. The reasonable conformity between the milled samples spectra and synthesized spectra indicated representativeness of physical mixtures with crystalline or amorphous domains in the estimation of apparent amorphous content in milled lactose. PMID- 27397870 TI - Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial-like anion transport. AB - The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well-documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally-regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate. More recently, however, we have shown that for the first 3-4 h after pupariation SGs undergo tremendous endocytosis and vacuolation followed by vacuole neutralization and membrane consolidation. Furthermore, from 8 to 10 h after puparium formation (APF) SGs display massive apocrine secretion of a diverse set of cellular proteins. Here, we show that during the period from 11 to 12 h APF, the prepupal glands are very active in calcium oxalate (CaOx) extrusion that resembles renal or nephridial excretory activity. We provide genetic evidence that Prestin, a Drosophila homologue of the mammalian electrogenic anion exchange carrier SLC26A5, is responsible for the instantaneous production of CaOx by the late prepupal SGs. Its positive regulation by the protein kinases encoded by fray and wnk lead to increased production of CaOx. The formation of CaOx appears to be dependent on the cooperation between Prestin and the vATPase complex as treatment with bafilomycin A1 or concanamycin A abolishes the production of detectable CaOx. These data demonstrate that prepupal SGs remain fully viable, physiologically active and engaged in various cellular activities at least until early pupal period, that is, until moments prior to the execution of PCD. PMID- 27397871 TI - In vitro culture of ovarian follicles from Peromyscus. AB - The ovarian follicle is the fundamental functional tissue unit of mammalian ovary. Each ovarian follicle contains one single oocyte. Isolation and in vitro culture of ovarian follicles to obtain fertilizable oocytes have been regarded as a promising strategy for women to combat infertility. The follicles from Peromyscus are considered as a better model than that from inbred mice for studying follicle culture. This is because Peromyscus mice are outbred (as with humans) with an increased life span. In this article, we reviewed studies on this subject conducted using Peromyscus follicles. These studies show that the conventional 2D micro-drop and 3D hanging-drop approaches established for in vitro culture of early preantral follicles from inbred mice are not directly applicable for cultivating the follicles from Peromyscus. However, the efficiency could be significantly improved by culturing multiple early preantral follicles in one hanging drop of Peromyscus ovarian cell-conditioned medium. It is further revealed that the mechanical heterogeneity in the extracellular matrix of ovary is crucial for developing early preantral follicles to the antral stage and for the subsequent ovulation to release cumulus-oocyte complex. These findings may provide valuable guidance for furthering the technology of in vitro follicle culture to restore fertility in the clinic. PMID- 27397873 TI - Probable Griseofulvin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms in a Child. AB - A 9-year-old boy presented with fever, rash, anterior cervical lymphadenopathy, high liver enzymes, atypical lymphocytosis, and eosinophilia (drug reaction with eosinophilia and systemic symptoms [DRESS]). His history was notable for having taken griseofulvin for 3 weeks prior to onset of these findings. He improved after treatment with oral prednisone. We present a rare case of probable DRESS secondary to griseofulvin. PMID- 27397872 TI - A novel HLA-B allele, HLA-B*13:91, was identified by sequencing-based typing in the CMDP. AB - The new allele HLA-B*13:91 was initially identified in a Chinese individual by sequence-based typing. PMID- 27397874 TI - Association between polychlorinated biphenyls and diabetes mellitus in the German HELPcB cohort. AB - AIMS: The aim of the present study was to examine whether there is an association between the prevalence of diabetes mellitus, the levels of HbA1c and the internal PCB burden of the initial 263 participants of HELPcB (Health Effects in High Level Exposure to PCB). Four waves of follow ups were examined with a cross sectional and a longitudinal approach between 2010 and 2013. HELPcB is a surveillance program for formerly PCB-exposed workers of a capacitor recycling company and other potentially affected people. METHODS: During 4 waves of follow up, medical history and blood samples were taken. Biomonitoring for PCB was conducted by gas chromatography coupled with mass spectrometry. Serum analysis of blood glucose, HbA1c, GAD, IAA, IA-2 and ICA were conducted at the centre of laboratory diagnostics of the local university hospital. RESULTS: The mean levels of PCB were comparable to other investigations of occupational cohorts like Persky et al. (2012). A logistic regression model showed higher prevalence rates in comparison to the German general population for diagnosed or undiagnosed diabetes mellitus for several PCB congeners in the second, third or fourth quartile of PCB burden. The adjusted odds ratio was significantly increased for PCB 52 at the third quartile (7.6; 95% CI: 1.4-41.0). A multiple linear regression model showed a significant influence of several PCB congeners on the HbA1c level at year 3 and 4. The development of HbA1c over time was examined with the same regression model applied to a longitudinal data set of 119 participants who met all 4 follow ups. An analysis of the autoantibodies GAD, IAA, IA-2 and ICA showed no association to PCB burden. CONCLUSIONS: In summary there is a detectable association between internal PCB burden and glucose metabolism in the cohort of HELPcB, however it is difficult to find a possible mechanism or a congener with outstanding influence. Further research and more follow ups for the HELPcB cohort are scheduled. PMID- 27397875 TI - Early citalopram treatment increases mortality due to left ventricular rupture in mice after myocardial infarction. AB - AIMS: Both anxiety and depression are common and independent outcome predictors in patients after myocardial infarction (MI). However, it is unclear whether and how anti-depressants influence remodeling after MI. Thus, we studied cardiac remodeling in mice after experimental MI under treatment with citalopram, a selective serotonin reuptake inhibitor widely used as antidepressant. METHODS AND RESULTS: Treatment with citalopram versus saline was applied via osmotic pump after coronary artery ligation. Two different groups were studied: early treatment during the healing phase (starting immediately after surgery), or late treatment in the remodeling phase (starting 7days after surgery). Late treatment did not change mortality or left ventricular remodeling after MI over the period of 6weeks. However, in the early treatment group mortality was increased in citalopram-treated mice predominantly due to left ventricle rupture without differences in infarct size. Remodeling 4weeks after MI was not altered by the treatment. Neither infiltration of inflammatory cells, as determined by FACS analysis of myocardial tissue, nor mRNA-expression of inflammatory cytokines changed 3days after MI in the early treatment group. However, extracellular matrix functioning was altered: There was a significant increase of MMP13 in citalopram treated animals after MI. Pretreatment with the MMP inhibitor PD 166793 prevented left ventricular ruptures and demonstrated a tendency to improved survival after citalopram treatment. CONCLUSIONS: Treatment with antidepressant citalopram in the acute but not in the late phase after MI significantly increased mortality in mice by disturbing early healing. Pharmacological MMP inhibition partially reversed the deleterious effects of citalopram. PMID- 27397877 TI - Preface. PMID- 27397878 TI - From Leg Transplantation by St Cosmas and St Damian to the Modern Era. PMID- 27397876 TI - Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction. AB - BACKGROUND: Increased reactive oxygen species (ROS) production is involved in the process of adverse cardiac remodeling and development of heart failure after myocardial infarction (MI). NADPH oxidase-2 (Nox2) is a major ROS source within the heart and its activity increases after MI. Furthermore, genetic deletion of Nox2 is protective against post-MI cardiac remodeling. Nox2 levels may increase both in cardiomyocytes and endothelial cells and recent studies indicate cell specific effects of Nox2, but it is not known which of these cell types is important in post-MI remodeling. METHODS AND RESULTS: We have generated transgenic mouse models in which Nox2 expression is targeted either to cardiomyocytes (cardio-Nox2TG) or endothelial cells (endo-Nox2TG). We here studied the response of cardio-Nox2TG mice, endo-Nox2TG mice and matched wild type littermates (WT) to MI induced by permanent left coronary artery ligation up to 4weeks. Initial infarct size assessed by magnetic resonance imaging (MRI) and cardiac dysfunction were similar among groups. Cardiomyocyte hypertrophy and interstitial fibrosis were augmented in cardio-Nox2TG compared to WT after MI and post-MI survival tended to be worse whereas endo-Nox2TG mice showed no significant difference compared to WT. CONCLUSIONS: These results indicate that cardiomyocyte rather than endothelial cell Nox2 may have the more important role in post-MI remodeling. PMID- 27397880 TI - Renal Transplantation at K.U. Leuven. PMID- 27397879 TI - The History of Transplantation at the Catholic University of Louvain-Belgium 1963 2003. PMID- 27397881 TI - Organ Transplantation Pioneers at the "Universite Libre de Bruxelles". PMID- 27397882 TI - History of transplantation at the University Hospital of Ghent Belgium 1965-2002. PMID- 27397883 TI - History of Solid Organ Transplantation at the University of Liege. PMID- 27397884 TI - History of Transplantation at the University Hospital of Antwerp. PMID- 27397885 TI - William Welch and his Personal History of Organ Transplantation at the Vrij Universiteit Van Brussel. PMID- 27397886 TI - Imaging of tumors and tumor-like lesions of the knee. AB - Tumors and tumor-like lesions of the knee are common conditions. Because the synovial membrane covers a large part of the knee, tumors and tumor-like lesions of the knee are mostly synovial. Magnetic resonance imaging (MRI) plays a major role in the assessment and characterization of these lesions. However, the diagnostic approach of these lesions must be performed systematically. First, the lesion must be precisely located, and then the anatomical structure involved must be determined. Finally, clinical background that includes the age of the patient, frequency of the disease and, if any, associated signs as well as MRI characteristics must be analyzed. In this review, we describe the anatomy of the knee and its compartments and provide a description of the main tumors and tumor like lesions of the knee. We present a diagnostic approach based on the location within the knee of the lesions and the anatomical structures involved. PMID- 27397887 TI - Giant vascular eccrine spiradenoma of the leg: MR imaging findings. PMID- 27397888 TI - Cellular Basis of Head Direction and Contextual Cues in the Insect Brain. AB - Animals rely upon integrated sensory information for spatial navigation. A question of wide importance in navigation is how sensory cues get transformed into neural codes that represent the animal's orientation within its proximal environment. Here, we investigated the possibility of head-direction coding in the central complex of the cockroach, Blaberus discoidalis. We used extracellular recordings in restrained animals that were rotated on a platform relative to a fixed landmark. The passive rotations allowed us to test for head-direction coding in the absence of self-generated motion cues. Our results indicate that individual cells in the central complex encode the animal's heading relative to a landmark's position in several ways. In some cells, directional tuning was established even in the absence of visual cues, suggesting that the directional code can be maintained solely based on the internal motion cues derived from the passive rotations. Additionally, some cells in the central complex encoded rotation-direction history, a navigational context cue, by increasing or decreasing the firing rate during the stationary periods following clockwise or counterclockwise rotations. Together, these results unveil head-direction cell like activity in the insect central complex, which highly resemble similarly functioning cells in the mammalian brain that encode head direction. We predict that the observed head-orientation coding and directionally sensitive cells are essential components of the brain circuitry mediating insect navigation. PMID- 27397891 TI - Patterned Contractile Forces Promote Epidermal Spreading and Regulate Segment Positioning during Drosophila Head Involution. AB - Epithelial spreading is a fundamental mode of tissue rearrangement occurring during animal development and wound closure. It has been associated either with the collective migration of cells [1, 2] or with actomyosin-generated forces acting at the leading edge (LE) and pulling the epithelial tissue [3, 4]. During the process of Drosophila head involution (HI), the epidermis spreads anteriorly to envelope the head tissues and fully cover the embryo [5]. This results in epidermal segments of equal width that will give rise to the different organs of the fly [6]. Here we perform a quantitative analysis of tissue spreading during HI. Combining high-resolution live microscopy with laser microsurgery and genetic perturbations, we show that epidermal movement is in part, but not solely, driven by a contractile actomyosin cable at the LE. Additional driving forces are generated within each segment by a gradient of actomyosin-based circumferential tension. Interfering with Hedgehog (Hh) signaling can modulate this gradient, thus suggesting the involvement of polarity genes in the regulation of HI. In particular, we show that disruption of these contractile forces alters segment widths and leads to a mispositioning of segments. Within the framework of a physical description, we confirm that given the geometry of the embryo, a patterned profile of active circumferential tensions can indeed generate propelling forces and control final segment position. Our study thus unravels a mechanism by which patterned tensile forces can regulate spreading and positioning of epithelial tissues. PMID- 27397889 TI - Inhibition of Lithium-Sensitive Phosphatase BPNT-1 Causes Selective Neuronal Dysfunction in C. elegans. AB - Lithium has been a mainstay for the treatment of bipolar disorder, yet the molecular mechanisms underlying its action remain enigmatic. Bisphosphate 3' nucleotidase (BPNT-1) is a lithium-sensitive phosphatase that catalyzes the breakdown of cytosolic 3'-phosphoadenosine 5'-phosphate (PAP), a byproduct of sulfation reactions utilizing the universal sulfate group donor 3' phosphoadenosine 5'-phosphosulfate (PAPS) [1-3]. Loss of BPNT-1 leads to the toxic accumulation of PAP in yeast and non-neuronal cell types in mice [4, 5]. Intriguingly, BPNT-1 is expressed throughout the mammalian brain [4], and it has been hypothesized that inhibition of BPNT-1 could contribute to the effects of lithium on behavior [5]. Here, we show that loss of BPNT-1 in Caenorhabditis elegans results in the selective dysfunction of two neurons, the bilaterally symmetric pair of ASJ chemosensory neurons. As a result, BPNT-1 mutants are defective in behaviors dependent on the ASJ neurons, such as dauer exit and pathogen avoidance. Acute treatment with lithium also causes dysfunction of the ASJ neurons, and we show that this effect is reversible and mediated specifically through inhibition of BPNT-1. Finally, we show that the selective effect of lithium on the nervous system is due in part to the limited expression of the cytosolic sulfotransferase SSU-1 in the ASJ neuron pair. Our data suggest that lithium, through inhibition of BPNT-1 in the nervous system, can cause selective toxicity to specific neurons, resulting in corresponding effects on behavior of C. elegans. PMID- 27397890 TI - Drosophila SLC5A11 Mediates Hunger by Regulating K(+) Channel Activity. AB - Hunger is a powerful drive that stimulates food intake. Yet, the mechanism that determines how the energy deficits that result in hunger are represented in the brain and promote feeding is not well understood. We previously described SLC5A11 a sodium/solute co-transporter-like-(or cupcake) in Drosophila melanogaster, which is required for the fly to select a nutritive sugar over a sweeter nonnutritive sugar after periods of food deprivation. SLC5A11 acts on approximately 12 pairs of ellipsoid body (EB) R4 neurons to trigger the selection of nutritive sugars, but the underlying mechanism is not understood. Here, we report that the excitability of SLC5A11-expressing EB R4 neurons increases dramatically during starvation and that this increase is abolished in the SLC5A11 mutation. Artificial activation of SLC5A11-expresssing neurons is sufficient to promote feeding and hunger-driven behaviors; silencing these neurons has the opposite effect. Notably, SLC5A11 transcript levels in the brain increase significantly when flies are starved and decrease shortly after starved flies are refed. Furthermore, expression of SLC5A11 is sufficient for promoting hunger driven behaviors and enhancing the excitability of SLC5A11-expressing neurons. SLC5A11 inhibits the function of the Drosophila KCNQ potassium channel in a heterologous expression system. Accordingly, a knockdown of dKCNQ expression in SLC5A11-expressing neurons produces hunger-driven behaviors even in fed flies, mimicking the overexpression of SLC5A11. We propose that starvation increases SLC5A11 expression, which enhances the excitability of SLC5A11-expressing neurons by suppressing dKCNQ channels, thereby conferring the hunger state. PMID- 27397892 TI - Dpp/BMP2-4 Mediates Signaling from the D-Quadrant Organizer in a Spiralian Embryo. AB - In some animal groups, the secondary embryonic axis is patterned by a small group of cells, often called an organizer, that signals to other cells to establish the correct pattern of cell fates. The Dpp/BMP2-4 pathway plays a central role in secondary axis patterning in many animals [1-11], but it has not been examined during early axial patterning in spiralian embryogenesis. This is a deeply conserved mode of development found in mollusks, annelids, nemerteans, entoprocts, and some marine platyhelminth groups (reviewed in [12, 13]). In the spiralian embryo of the mollusk Ilyanassa, we find that the Dpp ortholog (IoDpp) is expressed most strongly on the dorsal side, in cells of the embryonic organizer and its neighbors. Phospho-smad staining indicates that the pathway is active in all lineages during organizer signaling, but activation is strongest on the dorsal side. Knockdown of IoDpp by morpholino oligos prevents the development of all structures that require organizer signaling and ventralizes the embryo. Ectopic activation of the pathway can induce eyes and external shell, which require organizer signaling. These results indicate that Dpp/BMP2-4 signaling is a key part of the spiralian organizer and suggest similarity with other metazoan organizers. However, the fact that IoDpp/BMP2-4 is inducing, rather than repressing, the neuroectoderm is a surprising difference that may be conserved among spiralians. These results connect the spiralian organizer to this general aspect of secondary axis patterning but highlight the significant variation across animals in effects of the pathway on particular cell types and tissues. PMID- 27397894 TI - Identification of a Retinal Circuit for Recurrent Suppression Using Indirect Electrical Imaging. AB - Understanding the function of modulatory interneuron networks is a major challenge, because such networks typically operate over long spatial scales and involve many neurons of different types. Here, we use an indirect electrical imaging method to reveal the function of a spatially extended, recurrent retinal circuit composed of two cell types. This recurrent circuit produces peripheral response suppression of early visual signals in the primate magnocellular visual pathway. We identify a type of polyaxonal amacrine cell physiologically via its distinctive electrical signature, revealed by electrical coupling with ON parasol retinal ganglion cells recorded using a large-scale multi-electrode array. Coupling causes the amacrine cells to fire spikes that propagate radially over long distances, producing GABA-ergic inhibition of other ON parasol cells recorded near the amacrine cell axonal projections. We propose and test a model for the function of this amacrine cell type, in which the extra-classical receptive field of ON parasol cells is formed by reciprocal inhibition from other ON parasol cells in the periphery, via the electrically coupled amacrine cell network. PMID- 27397893 TI - Phagocytosis Enhances Lysosomal and Bactericidal Properties by Activating the Transcription Factor TFEB. AB - Macrophages internalize pathogens through phagocytosis, entrapping them into organelles called phagosomes. Phagosomes then fuse with lysosomes to mature into phagolysosomes, acquiring an acidic and hydrolytic lumen that kills the pathogens. During an ongoing infection, macrophages can internalize dozens of bacteria. Thus, we hypothesized that an initial round of phagocytosis might boost lysosome function and bactericidal ability to cope with subsequent rounds of phagocytosis. To test this hypothesis, we employed Fcgamma-receptor-mediated phagocytosis and endocytosis, which internalize immunoglobulin G (IgG)-opsonized particles and polyvalent IgG immune complexes, respectively. We report that Fcgamma receptor activation in macrophages enhances lysosome-based proteolysis and killing of subsequently phagocytosed E. coli compared to naive macrophages. Importantly, we show that Fcgamma receptor activation causes nuclear translocation of TFEB, a transcription factor that boosts expression of lysosome genes. Indeed, Fc receptor activation is accompanied by increased expression of specific lysosomal proteins. Remarkably, TFEB silencing represses the Fcgamma receptor-mediated enhancements in degradation and bacterial killing. In addition, nuclear translocation of TFEB requires phagosome completion and fails to occur in cells silenced for MCOLN1, a lysosomal Ca(2+) channel, suggesting that lysosomal Ca(2+) released during phagosome maturation activates TFEB. Finally, we demonstrate that non-opsonic phagocytosis of E. coli also enhances lysosomal degradation in a TFEB-dependent manner, suggesting that this phenomenon is not limited to Fcgamma receptors. Overall, we show that macrophages become better killers after one round of phagocytosis and suggest that phagosomes and lysosomes are capable of bi-directional signaling. PMID- 27397895 TI - Silent S-Type Anion Channel Subunit SLAH1 Gates SLAH3 Open for Chloride Root-to Shoot Translocation. AB - Higher plants take up nutrients via the roots and load them into xylem vessels for translocation to the shoot. After uptake, anions have to be channeled toward the root xylem vessels. Thereby, xylem parenchyma and pericycle cells control the anion composition of the root-shoot xylem sap [1-6]. The fact that salt-tolerant genotypes possess lower xylem-sap Cl(-) contents compared to salt-sensitive genotypes [7-10] indicates that membrane transport proteins at the sites of xylem loading contribute to plant salinity tolerance via selective chloride exclusion. However, the molecular mechanism of xylem loading that lies behind the balance between NO3(-) and Cl(-) loading remains largely unknown. Here we identify two root anion channels in Arabidopsis, SLAH1 and SLAH3, that control the shoot NO3( )/Cl(-) ratio. The AtSLAH1 gene is expressed in the root xylem-pole pericycle, where it co-localizes with AtSLAH3. Under high soil salinity, AtSLAH1 expression markedly declined and the chloride content of the xylem sap in AtSLAH1 loss-of function mutants was half of the wild-type level only. SLAH3 anion channels are not active per se but require extracellular nitrate and phosphorylation by calcium-dependent kinases (CPKs) [11-13]. When co-expressed in Xenopus oocytes, however, the electrically silent SLAH1 subunit gates SLAH3 open even in the absence of nitrate- and calcium-dependent kinases. Apparently, SLAH1/SLAH3 heteromerization facilitates SLAH3-mediated chloride efflux from pericycle cells into the root xylem vessels. Our results indicate that under salt stress, plants adjust the distribution of NO3(-) and Cl(-) between root and shoot via differential expression and assembly of SLAH1/SLAH3 anion channel subunits. PMID- 27397896 TI - Effect of high glucose, Porphyromonas gingivalis lipopolysaccharide and advanced glycation end-products on production of interleukin-6/-8 by gingival fibroblasts. AB - BACKGROUND AND OBJECTIVE: It is known that chronic periodontal infection can magnify the cytokine responses in patients with diabetes. Hyperglycemia increases the proinflammatory status, including the levels of advanced glycation end products (AGEs), in patients with periodontitis. However, whether AGEs have additional effects on the production of those proinflammatory cytokines in diabetic patients with periodontitis is still unknown. To examine in vitro the effect of hyperglycemia and AGEs on the amounts of interleukin (IL)-6 and IL-8 produced in periodontally infected gingiva, human gingival fibroblasts (HGFs) were stimulated with glucose, AGE-modified bovine serum albumin (AGE-BSA) and Porphyromonas gingivalis LPS in the present study. MATERIAL AND METHODS: Primary culture of HGFs was incubated with various concentrations of AGE-BSA (0, 50, 100 and 200 MUg/mL) and LPS (0, 10, 100 or 1000 ng/mL) at two different glucose concentrations - normal glucose (5 mm) and high glucose (25 mm). The amounts of IL-6 and IL-8 produced by HGFs were evaluated using ELISA. Expression of the AGE receptor on HGFs was determined by flow cytometry. RESULTS: High glucose stimulated a significant increase in the production of IL-6 and IL-8 by HGFs compared with normal glucose. This enhanced production of IL-6 and IL-8 could also be observed in the presence of LPS and/or AGE-BSA. When both LPS and AGE-BSA were present, especially at high concentrations (>= 500 MUg/mL of LPS and >= 25 MUg/mL of AGE-BSA), a synergistic effect on IL-8 production was found in the high glucose condition. CONCLUSIONS: A synergistic effect of the production of IL-8 could be induced in HGFs with the combination of high glucose, LPS and AGEs. PMID- 27397897 TI - Aortic arch involvement worsens the prognosis of type B aortic dissections. AB - OBJECTIVE: Medical management of acute aortic dissections limited to the descending thoracic aorta (AD-desc) is associated with acceptable outcomes. Uncertainty remains about whether acute type B aortic dissections involving the aortic arch (AD-arch) have an increased risk of retrograde extension into the ascending aorta or other dissection-related complications. This study compared outcomes of AD-arch with AD-desc managed medically. METHODS: Consecutive patients admitted from 2005 to 2014 with acute aortic dissections not involving the ascending aorta were retrospectively analyzed. Primary end points included dissection-related death and operative intervention. RESULTS: The study included 99 patients (63% men; mean age, 60 +/- 14 years) with acute aortic dissections. Dissections were limited to the aorta distal to the left subclavian artery (AD desc) in 79 patients (80%), and 20 (20%) had involvement of the left subclavian (n = 16), left common carotid (n = 1), or innominate (n = 3) arteries (AD-arch). Dissections ended proximal to the celiac artery in 30 patients (30%), between the celiac artery and aortic bifurcation in 36 (36%), and distal to the aortic bifurcation in 33 (33%). During medical management, further proximal extension into the arch occurred in two AD-arch patients and one AD-desc patient (P < .05), but proximal dissection into the ascending aorta occurred in only one AD-arch patient with Marfan disease. Compared with patients with AD-desc, those with AD arch were younger (53 +/- 12.5 vs 62 +/- 16 years; P < .01) and had more frequent early interventions (40% vs 19%; P = .047), cardiac complications (35% vs 11%; P < .01), and neurologic events (25% vs 6%; P < .01). Seven AD-arch patients (35%) and nine AD-desc patients (11%) died of dissection-related causes (P < .01). Among survivors, late interventions were performed in four of eight AD-arch patients (50%) and in six of 58 AD-desc patients (10%; P = .02). Medical treatment without intervention was successful in four AD-arch patients (20%) and in 52 AD-desc patients (66%; P < .001). Multivariate logistic regression retained arch involvement as the sole predictor of dissection-related death (odds ratio, 4.2; 95% confidence interval, 1.3-13.4) and failure of medical treatment (odds ratio, 7.7; 95% confidence interval, 2.5-29). The distal extent of dissection had no bearing on outcome. CONCLUSIONS: AD-arch dissections are associated with a higher risk of cardiac and neurologic events, need for early intervention, and dissection-related death than AD-desc dissections. Because further proximal dissections into the ascending aorta were rare in this study, medical management appears to be safe as the initial treatment of AD-arch dissections. However, surgeons should be aware of the increased risk of complications and the potential need for urgent interventions in these patients. PMID- 27397898 TI - A tug-of-war between tolerance and rejection - New evidence for 3'UTR HLA-G haplotypes influence in recurrent pregnancy loss. AB - HLA-G is a molecule essential to the maintenance of the maternal-fetal interface tolerance, thus contributing to a healthy pregnancy. Here we investigate the role of HLA-G single nucleotide polymorphisms (SNPs) and whether a specific HLA-G haplotype influence or not recurrent pregnancy loss (RPL) risk. A total of 296 DNA samples from RPL (N=140) and controls (N=156) were evaluated. The HLA-G 3'UTR region was sequenced and eight major SNPs were evaluated (14pb insertion/deletion, +3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, +3187A/G, +3196C/G). A high linkage disequilibrium (LD) among all pairs and a perfect LD between +3010C/G and +3142G/A (D'=1.0, r(2)=1.0) were observed. Our data showed an increased risk to +3010CC genotype carriers in comparison with control [odds ratio (OR) 2.05 95% confidence interval (CI) 1.05-4.00, p=0.035] and to a decreased risk of RPL in +3142CC genotype carriers (OR=0.49 95%CI 0.25-0.95, p=0.035) and +3187AG genotype carriers (OR=0.58 95%CI 0.35-0.94, p=0.029). A total of eight haplotypes were observed in the sample, being UTR-1 and UTR-2 the most represented. An association between UTR-1 haplotype carriers with a reduced risk of both RPL and secondary RPL was observed. Our results indicate that the HLA-G 3'UTR plays important roles in RPL and might be an important marker of susceptibility to this, and possible to other, pregnancy disorders. PMID- 27397899 TI - Current and future perspectives in imaging of venous thromboembolism. AB - Several thrombus imaging techniques for the diagnosis of venous thromboembolism (VTE) are available. The most prevalent forms of VTE are deep vein thrombosis of the lower extremities and pulmonary embolism. However, VTE may also occur at unusual sites such as deep veins of the upper extremity and the splanchnic and cerebral veins. Currently, the imaging techniques most widely used in clinical practice are compression ultrasonography and computed tomography (CT) pulmonary angiography. Moreover, single-photon emission CT, CT venography, positron emission tomography, and different magnetic resonance imaging (MRI) techniques, including magnetic resonance direct thrombus imaging, have been evaluated in clinical studies. This review provides an overview of the technique, diagnostic accuracy and potential pitfalls of these established and emerging imaging modalities for the different sites of venous thromboembolism. PMID- 27397900 TI - Ret mouse very large tumors (VLTs) display altered ratios of infiltrating memory to naive T cells: Roles in tumor expansion. AB - Melanoma is an aggressive skin cancer, however it is immunogenic. The size of the primary tumor is associated with the nodal metastases. Our goals were to characterize melanoma-associated antigens (MAAs) and tumor-infiltrating T lymphocytes (TILs) subsets in the few very large tumors (VLTs) developing in ret transgenic mice of melanoma. Tumors >700mg (VLTs) were investigated for MAAs and subsets of TILs. Immunohistochemistry and flow cytometry-based studies were performed to determine the infiltration patterns of T-lymphocytes in VLTs. It was observed that zinc fixative restores the antigenicity of the cell-surface markers of lymphocyte subpopulations without the need of antigen retrieval, whereas formalin-based fixative fails to restore the antigenicity in the presence of antigen retrieval in the immunohistochemistry. VLTs from ret mice express MAAs, such as Tyrosinase, TRP-1, TRP-2 and gp-100. The mean+/-standard deviation (S.D.) T-cell infiltration per 400 times-high power field in VLTs; CD4(+) (2.33+/-1.3), CD8(+) (2.00+/-1.0), and CD4(+) Foxp3(+) (2.5+/-0.5) regulatory T cells infiltration was exclusively restricted to the tumor stroma. Moreover, our flow cytometry-based data reveal that % mean+/-S.D. naive CD3(+) CD4(+) T cell infiltration (32.8+/-4.0%) was significantly larger than effector (25.8+/-2.8%, p<0.01) and central memory cells (16.1+/-3.7%, p<0.001) in VLTs. Similarly, between CD3(+) CD8(+) T cells, naive cells infiltrate (57.7+/-2.3%) in a significantly larger frequency than effector (5.0+/-0.4%, p<0.0001) and central memory cell (4.8+/-1.7%, p<0.0001) subsets. These results suggest that the VLTs from ret mice display lowered infiltration ratios between memory and naive T cells, which could be associated with the relatively large growth of VLTs. PMID- 27397901 TI - The non-linear association between low-level lead exposure and maternal stress among pregnant women. AB - BACKGROUND: Neuro-developmental impairments in the developing fetus due to exposure to low-level lead have been well documented. However, few studies have investigated the relation between maternal stress levels and low-level lead exposure among pregnant women. OBJECTIVES: To investigate the relation between maternal blood lead and stress levels during index pregnancy. METHODS: 1931 pregnant women (gestational week 28-36) were investigated using stratified cluster-sampling in Shanghai in 2010. Maternal life event stress and emotional stress were assessed using "Life-Event-Stress-Scale-for-Pregnant-Women" (LESPW) and "Symptom-Checklist-90-Revised" (SCL-90-R), respectively. Maternal whole blood lead levels were determined, and other data on covariates were obtained from maternal interviews and medical records. Two piecewise linear regression models were applied to assess the relations between blood lead and stress levels using a data-driven approach according to spline smoothing fitting of the data. RESULTS: Maternal blood lead levels ranged from 0.80 to 14.84MUg/dL, and the geometric mean was 3.97MUg/dL. The P-values for the two piecewise linear models against the single linear regression models were 0.010, 0.003 and 0.017 for models predicting GSI, depression and anxiety symptom scores, respectively. When blood lead levels were below 2.57MUg/dL, each unit increase in log10 transformed blood lead levels (MUg/dL) was associated with about 18% increase in maternal GSI, depression and anxiety symptom scores (PGSI=0.013, Pdepression=0.002, Panxiety=0.019, respectively). However, no significant relation was found when blood lead levels were above 2.57MUg/dL (all P-values>0.05). CONCLUSION: Our findings suggested a nonlinear relationship between blood lead and emotional stress levels among pregnant women. Emotional stress increased along with blood lead levels, and appeared to be plateaued when blood lead levels reached 2.57MUg/dL. PMID- 27397902 TI - MiR-214-3p attenuates cognition defects via the inhibition of autophagy in SAMP8 mouse model of sporadic Alzheimer's disease. AB - The autophagy process is the major cellular degradation pathway for long-lived proteins and organelles. Dysfunction of autophagy may lead to several neurodegenerative disorders. However, the regulation and function of autophagy in sporadic Alzheimer's disease (SAD) remain unclear. In this study, we established SAMP8 mouse as a suitable SAD model and performed microarray profiling to identify miR-214-3p as a SAD associated microRNA that was downregulated in hippocampal neurons of SAMP8 mice upon the induction of autophagy. Furthermore, decreased miR-214-3p level was detected in cerebrospinal fluid from SAD patients. Overexpression of miR-214-3p in primary neurons from SAMP8 mice inhibited autophagy, demonstrated by decreased levels of LC3betaII and Beclin1, and reduced number of GFP-LC3-positive autophagosome vesicles, and led to increased viability and decreased caspase-mediated apoptosis. Conversely, antagomiR-214-3p promoted autophagy and apoptosis in neurons from SAMP8 mice. Mechanistically, miR-214-3p negatively regulated Atg12 expression by targeting the 3'-untranslated region of Atg12. Treatment of SAMP8 mice with miR-214-3p attenuated neuronal apoptosis and improved behavioral performance. Taken together, these results suggest that miR 214-3p suppresses autophagy and alleviates hippocampal neuron apoptosis, which indicates that miR-214-3p represents a new potential neuroprotective factor for SAD. PMID- 27397903 TI - Influence of immobilization and forced swim stress on the neurotoxicity of lambda cyhalothrin in rats: Effect on brain biogenic amines and BBB permeability. AB - Experimental studies have been carried out on rats to understand the influence of immobilization stress (IMS), a psychological stressor and forced swim stress (FSS), a physical stressor in the neurotoxicity of lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid with extensive applications. No significant change in plasma corticosterone levels and blood brain barrier (BBB) permeability was observed in rats subjected to IMS (one session of 15min/day), FSS (one session of 3min/day) for 28days or LCT treatment (3.0mg/kg body weight, p.o. suspended in groundnut oil) for 3days (26th, 27th and 28th day) as compared to controls. Marginal changes in the levels of biogenic amines and their metabolites (NE, EPN, DA, HVA, DOPAC, 5-HT) in hypothalamus, frontal cortex, hippocampus, and corpus striatum were observed in rats subjected to IMS or FSS or LCT alone as compared to controls. It was interesting to note that pre-exposure to IMS or FSS followed by LCT treatment for 3days caused a marked increase in plasma corticosterone levels associated with disruption in the BBB permeability as compared to rats exposed to IMS or FSS or LCT alone. Pre-exposure to IMS or FSS followed by LCT treatment for 3days resulted to alter the levels of biogenic amines and their metabolites in hypothalamus, frontal cortex, hippocampus, and corpus striatum as compared to rats exposed to IMS or FSS or LCT alone. Although neurochemical changes were more intense in rats pre-exposed to IMS as compared to those subjected to FSS on LCT treatment, the results indicate that both psychological and physical stress could be important influencing factors in the neurotoxicity of LCT. PMID- 27397904 TI - Silicone medical adhesive removers for hyperkeratosis in epidermolysis bullosa. PMID- 27397905 TI - Relationship between frequency of eating and cardiovascular disease mortality in U.S. adults: the NHANES III follow-up study. AB - PURPOSE: This study examined longitudinal relationship between baseline daily eating frequency and all-cause and cardiovascular disease (CVD) mortality among U.S. adults. METHODS: The Third National Health and Nutrition Examination Survey (1988-1992) participants were followed through 2006. Nonpregnant adults >17 years old (n = 6884) whose dietary recall was of good quality and had fasted at least 8 hours before physical examinations were eligible for this analysis. Frequency of eating was derived from 24-hour dietary recalls. Main outcomes included all-cause and CVD mortality during follow-up, based on National Death Index data. RESULTS: During follow-up (median time: 176 months), 1280 subjects died, 503 of them from CVD. Adults reporting eating >=6 times/day had a lower hazard ratio for CVD mortality than those reporting eating 4 times/day (hazard ratio = 0.68; 95% confidence interval, 0.43-1.08; test for trend, P = .011). The gradient of CVD mortality risk by eating frequency was significant for the groups with >=2500 kcal of total energy intake (test for trend, P = .037). CONCLUSIONS: Eating frequency was inversely associated with CVD mortality, which was especially marked for people reporting high total energy intake. Nevertheless, public health recommendations should be cautious, as eating frequency was positively associated with total energy intake, which could promote weight gain. PMID- 27397906 TI - Nanoparticle-aided external beam radiotherapy leveraging the Cerenkov effect. AB - This study investigates the feasibility of exploiting the Cerenkov radiation (CR) present during external beam radiotherapy (EBRT) for significant therapeutic gain, using titanium dioxide (titania) nanoparticles (NPs) delivered via newly designed radiotherapy biomaterials. Using Monte Carlo radiation transport simulations, we calculated the total CR yield inside a tumor volume during EBRT compared to that of the radionuclides. We also considered a novel approach for intratumoral titania delivery using radiotherapy biomaterials (e.g. fiducials) loaded with NPs. The intratumoral distribution/diffusion of titania released from the fiducials was calculated. To confirm the CR induced enhancement in EBRT experimentally, we used 6MV radiation to irradiate human lung cancer cells with or without titania NPs and performed clonogenic assays. For a radiotherapy biomaterial loaded with 20MUg/g of 2-nm titania NPs, at least 1MUg/g could be delivered throughout a tumor sub-volume of 2-cm diameter after 14days. This concentration level could inflict substantial damage to cancer cells during EBRT. The Monte Carlo results showed the CR yield by 6MV radiation was higher than by the radionuclides of interest and hence greater damage might be obtained during EBRT. In vitro study showed significant enhancement with 6MV radiation and titania NPs. These preliminary findings demonstrate a potential new approach that can be used to take advantage of the CR present during megavoltage EBRT to boost damage to cancer cells. The results provide significant impetus for further experimental studies towards the development of nanoparticle-aided EBRT powered by the Cerenkov effect. PMID- 27397907 TI - Cleaning the grey zones of hospitals: A prospective, crossover, interventional study. AB - BACKGROUND: Environmental cleaning is a fundamental principle of infection prevention in hospitals, but its role in reducing transmission of health care acquired pathogens has been difficult to prove experimentally. In this study we analyze the influence of cleaning previously uncleaned patient care items, grey zones (GZ), on health care-acquired transmission rates. METHODS: The intervention consisted of specific GZ cleaning by an extra cleaner (in addition to routine cleaning) on 2 structurally different acute care medical wards for a period of 6 months each, in a crossover design. Data on health care-acquired transmissions of vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus, and Clostridium difficile were collected during both periods. Adjusted incidence rate ratios (IRRs) using Poisson regression were calculated to compare transmission of pathogens between both periods on both wards. RESULTS: During the intervention VRE transmission was significantly decreased (2-fold) on the ward where patients had fewer roommates; cleaning of GZ did not have any effect on the ward with multiple-occupancy rooms. There was no impact on methicillin-resistant S aureus transmission and only a nonsignificant decrease in transmission of C difficile. CONCLUSIONS: Our data provide evidence that targeted cleaning interventions can reduce VRE transmission when rooming conditions are optimized; such interventions can be cost-effective when the burden of VRE is significant. Enhanced cleaning interventions are less beneficial in the context of room sharing where many other factors contribute to transmission of pathogens. PMID- 27397909 TI - Journal Club: Antibiotic information application offers nurses quick support. PMID- 27397908 TI - Open and closed models of intensive care unit have different influences on infectious complications in a tertiary care center: A retrospective data analysis. AB - Infectious complications in the intensive care unit (ICU) are associated with higher morbidity, mortality, and increased health care use. Here, we report the results of implementing 2 different models (open vs closed) on infectious complications in the ICU. The closed ICU model was associated with 52% reduction in ventilator-associated pneumonia rate (P = .038) and 25% reduction in central line-associated bloodstream infection rate (P = .631). We speculate that a closed ICU model allows clinical leadership centralization that further facilitates standardized care delivery that translates into fewer infectious complications. PMID- 27397911 TI - Editor's Note. PMID- 27397910 TI - Survey finds improvement in cognitive biases that drive overtreatment of asymptomatic bacteriuria after a successful antimicrobial stewardship intervention. AB - BACKGROUND: Lack of guideline knowledge and cognitive biases are barriers that drive overtreatment of catheter-associated asymptomatic bacteriuria (ASB). We explored whether providers' knowledge and attitudes toward management of ASB differed before and after a multifaceted guidelines implementation intervention, reported elsewhere. METHODS: We surveyed providers' knowledge of guidelines, cognitive-behavioral constructs, and self-reported familiarity with the relevant Infectious Diseases Society of America guidelines. The survey was administered to providers in the preintervention (n = 169) and postintervention (n = 157) periods at the intervention site and postintervention (n = 65) at the comparison site. RESULTS: At the intervention site, the mean knowledge score increased significantly during the postintervention period (from 57.5%-69.9%; P < .0001) and fewer providers reported following incorrect cognitive cues (pyuria and organism type) for treatment of ASB. The knowledge of guidelines was higher in the postintervention sample after adjusting for provider type in the multiple linear regression analysis. Cognitive behavioral constructs (ie, self-efficacy, behavior, social norms, and risk perceptions) and self-reported familiarity with the guidelines also significantly improved during the postintervention period. CONCLUSIONS: We identified and targeted specific barriers that drive overtreatment of ASB. Guideline implementation interventions targeting cognitive biases are essential for encouraging the application of ASB guidelines into practice. PMID- 27397913 TI - Editor's Note. PMID- 27397912 TI - Healthy Weight in Lesbian and Bisexual Women Aged 40 and Older: An Effective Intervention in 10 Cities Using Tailored Approaches. AB - BACKGROUND: Lesbian and bisexual women are more likely to be overweight or obese than heterosexual women, leading to increased weight-related health risks. METHODS: Overweight women aged 40 or older who self-identified as lesbian, bisexual, or "something else" participated in five pilot interventions of 12 or 16 weeks' duration. These tailored interventions took place at lesbian and bisexual community partner locations and incorporated weekly group meetings, nutrition education, and physical activity. Three sites had non-intervention comparison groups. Standardized questionnaires assessed consumption of fruits and vegetables, sugar-sweetened beverages, alcohol, physical activity, and quality of life. Weight and waist-to-height ratio were obtained through direct measurement or self-report. ANALYTICAL PLAN: Within-person changes from pre-intervention to post-intervention were measured using paired comparisons. Participant characteristics that influenced the achievement of nine health objectives were analyzed. Achievement of health objectives across three program components (mindfulness approach, gym membership, and pedometer use) was compared with the comparison group using generalized linear models. RESULTS: Of the 266 intervention participants, 95% achieved at least one of the health objectives, with 58% achieving three or more. Participants in the pedometer (n = 43) and mindfulness (n = 160) programs were more likely to increase total physical activity minutes (relative risk [RR], 1.67; 95% confidence interval [CI], 1.18 2.36; p = .004; RR, 1.38; 95% CI, 1.01-1.89; p = .042, respectively) and those in the gym program (n = 63) were more likely to decrease their waist-to-height ratio (RR, 1.89; 95% CI, 0.97-3.68, p = .06) compared with the comparison group (n = 67). CONCLUSION: This effective multisite intervention improved several healthy behaviors in lesbian and bisexual women and showed that tailored approaches can work for this population. PMID- 27397914 TI - Two Tailored Provider Curricula Promoting Healthy Weight in Lesbian and Bisexual Women. AB - PURPOSE: Provider curricula to reduce potential weight bias or stigma in treating lesbian and bisexual (LB) women who are overweight or obese were pilot-tested in two unique settings. Trainings used LB cultural competency and motivational interviewing techniques to improve provider-patient interactions. METHODS: Two training formats were used: Clinic Format and Academic Format. Clinic Format training was pilot tested at Lyon-Martin Health Services, a Program of HealthRight360, a community health center serving women, lesbians, and transgender people in San Francisco and in two community settings. Academic Format training was pilot tested by the Mautner Project of Whitman-Walker Health with physicians, medical residents, and students at Georgetown, George Washington, Howard, and Vanderbilt Universities. Both programs measured provider knowledge and attitude change. RESULTS: Both programs saw significant percentage point gains in knowledge about LB women's avoidance of health care based on body size. Participants in the Academic Format program saw the greatest gain in knowledge about understanding health care avoidance (30 percentage point increase), whereas Clinic Format program participants gained most in understanding how to appropriately discuss weight loss with patients (23 percentage point increase). CONCLUSIONS: Both programs increased provider knowledge about the barriers to health care facing LB women who are overweight and obese, reducing the potential for future negative interactions. However, the two programs differed in how they conceptualized the relationship between weight and health, likely contributing to differences in knowledge gain among participants at each site. Future studies should test differences between the two formats across site type or staff baseline knowledge differences. PMID- 27397915 TI - Healthy Weight: A New Tailored Approach for Lesbian and Bisexual Women. PMID- 27397916 TI - Recruitment and Participation of Older Lesbian and Bisexual Women in Intervention Research. AB - BACKGROUND: Very little research has addressed issues of recruitment and participation of lesbian and bisexual (LB) women, aged 40 and older, into research studies. This study is based on a larger cross-site intervention study that recruited women from five geographic regions in the United States for culturally specific LB healthy weight programs, lasting 12 or 16 weeks. METHODS: Principal investigators (PIs) of the five intervention programs completed a questionnaire on recruitment and participation strategies and barriers. Participant data on completion and sociodemographic variables were compiled and analyzed. RESULTS: The recruitment strategies the programs' PIs identified as most useful included word-of-mouth participant referrals, emails to LB participants' social networks, and use of electronic health records (at the two clinic-based programs) to identify eligible participants. Flyers and web postings were considered the least useful. Once in the program, participation and completion rates were fairly high (approximately 90%), although with varying levels of engagement in the different programs. Women who were younger or single were more likely to drop out. Women with disabilities had a lower participation/completion rate (82%) than women without any disability (93%). Dropouts were associated with challenges in scheduling (time of day, location) and changes in health status. CONCLUSIONS: Implementation of key strategies can improve both recruitment and participation, but there is a great need for further study of best practices to recruit and promote participation of LB women for health intervention research. PMID- 27397917 TI - Effects of Mindfulness Interventions on Health Outcomes in Older Lesbian/Bisexual Women. AB - PURPOSE: Lesbian and bisexual (LB) women are at higher risk for obesity, but no reported interventions focus on older LB women who are overweight or obese. The Healthy Weight in Lesbian and Bisexual Women study funded five programs (n = 266 LB women age >=40); two examined effects of mindfulness interventions on health outcomes. METHODS: Analysis of variance and regression measured the impact of mindfulness-based programs on health behaviors and quality of life (MCS). Outcomes were also compared between intervention sites (mindfulness vs. standard weight loss approaches). RESULTS: Mindful Eating Questionnaire (MEQ) subscale scores improved significantly from preassessment to postassessment in mindfulness interventions. LB women who reported an increase (top tertile) in mindful eating had the most significant increase in MCS scores (35.3%) compared with those with low gains (low and medium tertile) in mindfulness (3.8%). MEQ score increase predicted 40.8% of the variance (adjusted) in MCS score, R(2) = .431, F(6,145) = 18.337, p < .001. Top tertile increases in mindfulness were significantly related to increases in physical activity and some nutrition outcomes. Mindfulness intervention sites showed within-person improvements in MCS and fruit and vegetable intake, whereas standard intervention sites showed within-person decreases in alcohol intake and increases in physical activity level. CONCLUSIONS: Although weight loss was not a primary outcome at the mindfulness sites, small but significant weight loss and weight-to-height ratio decreases were reported at all five sites. Increases in mindfulness were associated with a number of significant self-reported health improvements, including a great increase in perceived mental health quality of life. Mindfulness may be a promising practice to address health issues in aging LB women. PMID- 27397918 TI - "I Have to Age in This Body": Lesbian and Bisexual Older Women's Perspectives on a Health Behavior Intervention. AB - BACKGROUND: Despite the body of literature that suggests lesbian and bisexual (LB) women are more likely to be overweight or obese than heterosexual women and the overwhelming evidence that tailored interventions are most effective at changing behavior, a vacuum of culturally appropriate programs designed specifically for LB women still exists. The purpose of this study was to qualitatively examine LB women's perceptions of Project LOLA (Living Out, Living Actively), a 16-week intentional health promotion program tailored specifically for LB women aged 40 and older. METHODS: Researchers conducting this qualitative descriptive study employed a template approach to text analysis to capture insights into participants' perceptions of Project LOLA. Data were derived from two primary sources: weekly support group facilitator notes of participants' comments and participant focus group interviews conducted at the conclusion of the study. PEN-3, an ecologically oriented model that identifies individual, family, community, and systemic influences on behavior change, guided the analysis. FINDINGS: Study participants emphasized the importance of incorporating culture into health interventions for LB women. They valued having a safe space to talk about their health issues and health-related changes. Interacting with people who understood the culturally specific norms of the LB community was cited as particularly beneficial. CONCLUSIONS: Interventions tailored to LB women may generate stronger results and/or be better received if they are designed in a culturally relevant and supportive manner. Such interventions hold promise as a tool to help address health disparities faced by this population. PMID- 27397919 TI - Program Design for Healthy Weight in Lesbian and Bisexual Women: A Ten-City Prevention Initiative. AB - PURPOSE: Adult lesbian and bisexual (LB) women are more likely to be obese than adult heterosexual women. To address weight- and fitness-related health disparities among older LB women using culturally appropriate interventions, the Office on Women's Health (OWH) provided funding for the program, Healthy Weight in Lesbian and Bisexual Women (HWLB): Striving for a Healthy Community. This paper provides a description of the interventions that were implemented. METHODS: Five research organizations partnered with lesbian, gay, bisexual, and transgender community organizations to implement healthy weight interventions addressing the needs of LB women 40 years and older. The interventions incorporated evidence-based recommendations related to physical activity and nutrition. Each group intervention developed site-specific primary objectives related to the overall goal of improving the health of LB women and included weight and waist circumference reduction as secondary objectives. A 57-item core health survey was administered across the five sites. At a minimum, each program obtained pre- and post-program assessments. RESULTS: Each program included the OWH-required common elements of exercise, social support, and education on nutrition and physical activity, but adopted a unique approach to deliver intervention content. CONCLUSION: This is the first time a multisite intervention has been conducted to promote healthy weight in older LB women. Core measurements across the HWLB programs will allow for pooled analyses, and differences in study design will permit analysis of site-specific elements. The documentation and analysis of the effectiveness of these five projects will provide guidance for model programs and future research on LB populations. PMID- 27397920 TI - The "Something Else" of Sexual Orientation: Measuring Sexual Identities of Older Lesbian and Bisexual Women Using National Health Interview Survey Questions. AB - BACKGROUND: Terminology related to sexuality and gender is constantly evolving, and multiple factors are at play when individuals answer questions on surveys. METHODS: We examined patterns of responding to the National Health Interview Survey (NHIS) sexual identity questions in a multisite health intervention study for lesbian and bisexual women aged 40 to 84 years. RESULTS: Of 376 participants, 80% (n = 301) chose "lesbian or gay," 13% (n = 49) selected "bisexual," 7% (n = 25) indicated "something else," and 1 participant chose "don't know the answer." In response to the follow-up question for women who said "something else" or "don't know," most (n = 17) indicated that they were "not straight, but identify with another label." One participant chose "transgender, transsexual, or gender variant," five chose "You do not use labels to identify yourself," and three chose "you mean something else." Lesbian, bisexual, and "something else" groups were compared across demographic and health-related measures. Women who reported their sexual identity as "something else" were younger, more likely to have a disability, more likely to be in a relationship with a male partner, and had lower mental health quality of life than women who reported their sexual identity as lesbian or bisexual. CONCLUSIONS: Respondents who answer "something else" pose challenges to analysis and interpretation of data, but should not be discarded from samples. Instead, they may represent a subset of the community that views sexuality and gender as fluid and dynamic concepts, not to be defined by a single label. Further study of the various subsets of "something else" is warranted, along with reconsideration of the NHIS question options. PMID- 27397921 TI - Obese But Fit: The Relationship of Fitness to Metabolically Healthy But Obese Status among Sexual Minority Women. AB - PURPOSE: The purpose of this study was to describe fitness characteristics of metabolically healthy sexual minority women who are obese. METHODS: As part of the Healthy Weight in Lesbian and Bisexual Women Initiative funded by the U.S. Office on Women's Health, one site enrolled self-identified lesbian or bisexual women age 40 and older in a randomized controlled trial that evaluated interventions to improve health. Women with waist-to-height ratio of 0.5 or greater were classified as obese. Women without diabetes or cardiovascular disease and with normal range fasting blood level measurements of glucose, triglycerides, high-density cholesterol, and blood pressure were classified as metabolically healthy but obese (MHO). Otherwise, women were classified as metabolically unhealthy obese (MUHO). Fitness measurements included predicted VO2 maximum, 1-minute heart rate recovery, and strength (single maximal leg lift and chest press). Self-reported demographic and physical activity level data were obtained by standardized questionnaires. RESULTS: Of the 53 participants who completed the eligibility screener in Columbia, Missouri, 47 were enrolled in the study (89% participation proportion) with 45 categorized as obese. Approximately one-third (38%) were MHO. The majority of MHO and MUHO participants ranked poor or very poor on a composite fitness score that included measures of strength, flexibility, and aerobic fitness (75.0% and 77.8%, respectively). In the logistic regression models, better 1-minute heart rate recovery after peak exercise performance was significantly associated with MHO individuals (odds ratio, 2.92; 95% CI, 1.13-9.10) compared with MUHO. No other fitness measure was significantly different between the two groups. CONCLUSION: Consistent with other studies, we identified more than one-third of our obese sexual minority women as MHO. Fitness measures may be potential predictors of MHO status because one measure, heart rate recovery, was significantly associated with MHO status. With the population prevalence of obesity high and even higher among lesbian or bisexual women, sexual minority women are an ideal population for a longitudinal study to better understand MHO characteristics. PMID- 27397922 TI - Attention and cognitive penetrability: The epistemic consequences of attention as a form of metacognitive regulation. AB - A recent approach to the cognitive penetrability of perception, i.e. the possibility that perception is shaped top-down by high-level cognitive states such as beliefs and desires, proposes to understand the phenomenon on the basis of its consequences, among which there is a challenge for the epistemic role of perceptual experience in justifying beliefs (Stokes, 2015). In this paper, I argue that some attentional phenomena qualify as cases of cognitive penetrability under this consequentialist approach. I present a popular theory of attention, the biased-competition theory, on which basis I establish that attention is a form of metacognitive regulation. I argue that attention (as metacognitive regulation) involves the right kind of cognitive-perceptual relation and leads to the same epistemic consequences as other more traditional versions of cognitive penetrability. PMID- 27397923 TI - Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts. AB - BACKGROUND: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts. METHODS: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or high-dose (5 mg/day) sublingual HDM extracts for 2 weeks, followed by an additional week of intranasal exposure. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, cytokine levels in the BALF and lymph node cell culture supernatants, and allergen-specific antibodies were measured. Lung histology was also investigated. RESULTS: In mice sensitized for 5 weeks, high-dose SLIT ameliorated AHR, airway eosinophilia and goblet cell metaplasia. In mice sensitized for 3 weeks, even low dose SLIT ameliorated AHR and airway eosinophilia. Th2 cytokine levels in culture supernatants of submandibular lymph node cells in high-dose SLIT mice decreased, whereas IL-10 levels increased. Total IgA in BALF increased in mice sensitized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks. CONCLUSIONS: These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation. PMID- 27397924 TI - Enantioselective gas chromatography with functionalized cyclodextrins as chiral selectors. Fundamentals of the measurement of absolute association constants using capillary columns. AB - Chiral capillary GC columns containing different amounts of octakis(6-O-tert butyldimethylsilyl-2,3-di-O-acetil)-gamma-cyclodextrin as chiral selector dissolved in a polymeric matrix were constructed with the aim of determining enantiomeric association constants between a group of well resolved chiral N trifluoroacetyl amino acid methyl esters and this specific selector at different temperatures. The most relevant sources of uncertainties in the experimental data (hold-up and retention times, and column phase ratios at each temperature) were assessed. These cyclodextrin-based columns are known to enantioseparate a wide variety of chemical compounds, thus, the measurement of the absolute enantioselective constants of a group of solutes with this selector can be useful for systematic studies aimed to a general understanding about how these selectors work. These absolute association constants were estimated from data collected from very simplified experimental systems, and by using the fundamental gas liquid chromatography equations. PMID- 27397925 TI - Laser desorption-ion mobility spectrometry as a useful tool for imaging of thin layer chromatography surface. AB - We present a novel method for coupling thin layer chromatography (TLC) with ion mobility spectrometry (IMS) using laser desorption technique (LD). After separation of the compounds by TLC, the TLC surface was sampled by the LD-IMS without any further manipulation or preparation. The position of the laser was fixed and the TLC plate was moved in desired directions by the motorized micro positioning stage. The method was successfully applied to analyze the TLC plates containing explosives (tri nitro toluene, 1,3,5-trinitro- 1,3,5 triazacyclohexane, pentaerythritol tetranitrate, 2,4-dinitro toluene and 3,4 dinitro toluene), amino acids (alanine, proline and isoleucine), nicotine and diphenylamine mixtures and detection limits for these compounds were determined. Combination of TLC with LD-IMS technique offers additional separation dimension, allowing separation of overlapping TLC analytes. The time for TLC sampling by LD IMS was less than 80s. The scan rate for LD is adjustable so that fast and effective analysis of the mixtures is possible with the proposed method. PMID- 27397926 TI - Model-based high-throughput design of ion exchange protein chromatography. AB - This work describes the development of a model-based high-throughput design (MHD) tool for the operating space determination of a chromatographic cation-exchange protein purification process. Based on a previously developed thermodynamic mechanistic model, the MHD tool generates a large amount of system knowledge and thereby permits minimizing the required experimental workload. In particular, each new experiment is designed to generate information needed to help refine and improve the model. Unnecessary experiments that do not increase system knowledge are avoided. Instead of aspiring to a perfectly parameterized model, the goal of this design tool is to use early model parameter estimates to find interesting experimental spaces, and to refine the model parameter estimates with each new experiment until a satisfactory set of process parameters is found. The MHD tool is split into four sections: (1) prediction, high throughput experimentation using experiments in (2) diluted conditions and (3) robotic automated liquid handling workstations (robotic workstation), and (4) operating space determination and validation. (1) Protein and resin information, in conjunction with the thermodynamic model, is used to predict protein resin capacity. (2) The predicted model parameters are refined based on gradient experiments in diluted conditions. (3) Experiments on the robotic workstation are used to further refine the model parameters. (4) The refined model is used to determine operating parameter space that allows for satisfactory purification of the protein of interest on the HPLC scale. Each section of the MHD tool is used to define the adequate experimental procedures for the next section, thus avoiding any unnecessary experimental work. We used the MHD tool to design a polishing step for two proteins, a monoclonal antibody and a fusion protein, on two chromatographic resins, in order to demonstrate it has the ability to strongly accelerate the early phases of process development. PMID- 27397927 TI - DNA hypomethylation and its mediation in the effects of fine particulate air pollution on cardiovascular biomarkers: A randomized crossover trial. AB - BACKGROUND: Short-term exposure to fine particulate matter (PM2.5) air pollution has been associated with altered DNA methylation in observational studies, but it remains unclear whether this change mediates the effects on cardiovascular biomarkers. OBJECTIVE: To examine the impact of ambient PM2.5 on gene-specific DNA methylation and its potential mediation in the acute effects of PM2.5 on cardiovascular biomarkers. METHODS: We designed a randomized, double-blind crossover trial using true or sham air purifiers for 48h among 35 healthy college students in Shanghai, China, in 2014. We measured blood global methylation estimated in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements, methylation in ten specific genes, and ten cardiovascular biomarkers. We used linear mixed-effect models to examine the associations between PM2.5 and methylation. We also performed causal mediation analyses to evaluate the potential mediation of methylation in the associations between PM2.5 and biomarkers. RESULTS: Air purification increased DNA methylation in repetitive elements and all candidate genes. An IQR increase (64MUg/m(3)) in PM2.5 was significantly associated with reduction of methylation in LINE-1 (1.44%), one pro inflammatory gene (CD40LG, 9.13%), two pro-coagulant genes (F3, 15.20%; SERPINE1, 3.69%), and two pro-vasoconstriction genes (ACE, 4.64%; EDN1, 9.74%). There was a significant mediated effect (17.82%, P=0.03) of PM2.5 on sCD40L protein through CD40LG hypomethylation. Hypomethylation in other candidate genes generally showed positive but non-significant mediation. CONCLUSIONS: This intervention study provided robust human evidence that ambient PM2.5 could induce rapid decreases in DNA methylation and consequently partly mediate its effects on cardiovascular biomarkers. PMID- 27397928 TI - Regional comparison of organophosphate flame retardant (PFR) urinary metabolites and tetrabromobenzoic acid (TBBA) in mother-toddler pairs from California and New Jersey. AB - The use of alternative chemical flame retardants in consumer products is increasing as the result of the phase-out of polybrominated diphenyl ethers. Today, the most commonly detected alternatives in residential furniture include the organophosphate flame retardants (PFRs) and the Firemaster (R) 550 mixture (FM550). Urinary levels of dialkyl and diaryl phosphate esters, and 2-ethylhexyl tetrabromobenzoate (EH-TBB) have been used as biomarkers of human exposure to PFRs and FM550, respectively. In a previous study, we demonstrated that toddlers had significantly higher levels of PFRs relative to their mothers in a cohort from New Jersey; however, it is unclear if there are regional differences in exposure. It is possible that exposure to PFRs may be higher in California relative to other US States due to the California flammability standard, as was seen previously observed for PBDEs. In the current study, we examined urinary levels of PFR metabolites and TBBA in 28 mother-child pairs from California, USA, collected in 2015, and compared them with levels measured in our previous study from New Jersey. Urine samples were extracted using solid-phase extraction and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1,3-dichloro 2propyl) phosphate (BDCIPP) and BCIPHIPP conjugates were detected in 100% of mother and child urine samples, while bis(1-chloro-2-propyl) phosphate (BCIPP), tert-butyl-phenyl phenyl phosphate (tb-PPP) and TBBA were detected in < 50% of samples. Interestingly, BCIPHIPP conjugates were detected in 100% of the urine samples, suggesting ubiquitous exposure to the parent compound, tris(1-chloro-2 propyl) phosphate (TCIPP). The current study found significantly higher BDCIPP levels in California toddlers and higher and ip-PPP levels in mothers as compared to the New Jersey cohort, which may be reflective of California's furniture flammability standard. For example, BDCIPP levels in California children were 2.4 times higher than those in New Jersey children. Consistent with our previous work, the current study showed higher PFR and EH-TBB exposure in children, likely due to increased hand-mouth behavior. Children's DPHP and BDCIPP levels, on average, were 5.9 times and 15 times those of their mothers. Positive correlations between paired mothers and their children were shown for DPHP and BCIPHIPP conjugates but not BDCIPP or ip-PPP. In the children, several predictors of hand-mouth behavior were associated with BDCIPP, DPHP and ip-PPP urine levels, but no associations were observed with BCIPHIPP conjugates. PMID- 27397929 TI - Personal exposure to fine particulate matter and blood pressure: A role of angiotensin converting enzyme and its DNA methylation. AB - BACKGROUND: The underlying intermediate mechanisms about the association between fine particulate matter (PM2.5) air pollution and blood pressure (BP) were unclear. Few epidemiological studies have explored the potential mediation effects of angiotensin-converting enzyme (ACE) and its DNA methylation. METHODS: We designed a longitudinal panel study with 4 follow-ups among 36 healthy college students in Shanghai, China from December 17, 2014 to July 11, 2015. We measured personal real-time exposure to PM2.5, serum ACE level, and blood methylation of ACE gene and the repetitive elements. We applied linear mixed-effects models to examine the effects of PM2.5 on ACE protein, DNA methylation and BP markers. Furthermore, we conducted mediation analyses to evaluate the potential pathways. RESULTS: An interquartile range increase (26.78MUg/m(3)) in 24-h average exposure to PM2.5 was significantly associated with 1.12 decreases in ACE average methylation (%5mC), 13.27% increase in ACE protein, and increments of 1.13mmHg in systolic BP, 0.66mmHg in diastolic BP and 0.82mmHg in mean arterial pressure. ACE hypomethylation mediated 11.78% (P=0.03) of the elevated ACE protein by PM2.5. Increased ACE protein accounted for 3.90~13.44% (P=0.35~0.68) of the elevated BP by PM2.5. Repetitive-element methylation was also decreased but did not significantly mediate the association between PM2.5 and BP. CONCLUSIONS: This investigation provided strong evidence that short-term exposure to PM2.5 was significantly associated with BP, ACE protein and ACE methylation. Our findings highlighted a possible involvement of ACE and ACE methylation in the effects of PM2.5 on elevating BP. PMID- 27397930 TI - Buildings, Beneficial Microbes, and Health. AB - Bacteria and fungi in buildings exert an influence on the human microbiome through aerosol deposition, surface contact, and human and animal interactions. As the identities and functions of beneficial human microbes emerge, the consequences of building design, operation, and function must be understood to maintain the health of occupants in buildings. PMID- 27397931 TI - Unh1, an Ustilago maydis Ndt80-like protein, controls completion of tumor maturation, teliospore development, and meiosis. AB - In this study, Ustilago maydis Ndt80 homolog one, unh1, of the obligate sexual pathogen U. maydis,is described. Unh1 is the sole Ndt80-like DNA-binding protein inU. maydis. In this model basidiomycete, Unh1 plays a role in sexual development, influencing tumor maturation, teliospore development and subsequent meiotic completion. Teliospore formation was reduced in deletion mutants, and those that did form had unpigmented, hyaline cell walls, and germinated without completing meiosis. Constitutively expressing unh1 in haploid cells resulted in abnormal pigmentation, when grown in both potato dextrose broth and minimal medium, suggesting that pigmentation may be triggered by unh1 in U. maydis. The function of Unh1 in sexual development and pigment production depends on the presence of the Ndt80-like DNA-binding domain, identified within Unh1. In the absence of this domain, or when the binding domain was altered with targeted amino acid changes, ectopic expression of Unh1 failed to complement the unh1 deletion with regards to pigment production and sexual development. An investigation of U. maydis genes with upstream motifs similar to Ndt80 recognition sequences revealed that some have altered transcript levels in Deltaunh1 strains. We propose that the first characterized Ndt80-like DNA-binding protein in a basidiomycete, Unh1, acts as a transcription factor that is required for teliospore maturation and the completion of meiosis in U. maydis. PMID- 27397932 TI - Performance and grain yield stability of maize populations developed using marker assisted recurrent selection and pedigree selection procedures. AB - A marker-assisted recurrent selection (MARS) program was undertaken in sub Saharan Africa to improve grain yield under drought-stress in 10 biparental tropical maize populations. The objectives of the present study were to evaluate the performance of C1S2-derived hybrids obtained after three MARS cycles (one cycle of recombination (C1), followed by two generations of selfing (S2), and to study yield stability under both drought-stress (DS) and well-watered (WW) conditions. For each of the 10 populations, we evaluated hybrids developed by crossing 47-74 C1S2 lines advanced through MARS, the best five S5 lines developed through pedigree selection, and the founder parents with a single-cross tester from a complementary heterotic group. The hybrids and five commercial checks were evaluated in Kenya under 1-3 DS and 3-5 WW conditions with two replications. Combined across DS locations, the top 10 C1S2-derived hybrids from each of the 10 biparental populations produced 0.5-46.3 and 11.1-55.1 % higher mean grain yields than hybrids developed using pedigree selection and the commercial checks, respectively. Across WW locations, the best 10 hybrids derived from C1S2 of each population produced 3.4-13.3 and 7.9-36.5 % higher grain yields than hybrids derived using conventional pedigree breeding and the commercial checks, respectively. Mean days to anthesis of the best 10 C1S2 hybrids were comparable to those of hybrids developed using the pedigree method, the founder parents and the commercial checks, with a maximum difference of 3.5 days among the different groups. However, plant height was significantly (P < 0.01) different in most pairwise comparisons. Our results showed the superiority of MARS over pedigree selection for improving diverse tropical maize populations as sources of improved lines for stress-prone environments and thus MARS can be effectively integrated into mainstream maize breeding programs. PMID- 27397933 TI - Rapid Erosion Modeling in a Western Kenya Watershed using Visible Near Infrared Reflectance, Classification Tree Analysis and 137Cesium. AB - Human induced soil erosion has severe economic and environmental impacts throughout the world. It is more severe in the tropics than elsewhere and results in diminished food production and security. Kenya has limited arable land and 30 percent of the country experiences severe to very severe human induced soil degradation. The purpose of this research was to test visible near infrared diffuse reflectance spectroscopy (VNIR) as a tool for rapid assessment and benchmarking of soil condition and erosion severity class. The study was conducted in the Saiwa River watershed in the northern Rift Valley Province of western Kenya, a tropical highland area. Soil 137Cs concentration was measured to validate spectrally derived erosion classes and establish the background levels for difference land use types. Results indicate VNIR could be used to accurately evaluate a large and diverse soil data set and predict soil erosion characteristics. Soil condition was spectrally assessed and modeled. Analysis of mean raw spectra indicated significant reflectance differences between soil erosion classes. The largest differences occurred between 1,350 and 1,950 nm with the largest separation occurring at 1,920 nm. Classification and Regression Tree (CART) analysis indicated that the spectral model had practical predictive success (72%) with Receiver Operating Characteristic (ROC) of 0.74. The change in 137Cs concentrations supported the premise that VNIR is an effective tool for rapid screening of soil erosion condition. PMID- 27397934 TI - A Comprehensive Examination of Changes in Psychological Flexibility Following Acceptance and Commitment Therapy for Chronic Pain. AB - Acceptance and commitment therapy (ACT) for chronic pain aims to improve patient functioning by fostering greater psychological flexibility. While promising, ACT treatment process research in the context of chronic pain so far has only focused on a few of the processes of psychological flexibility. Therefore, this study aimed to more comprehensively examine changes in processes of psychological flexibility following an ACT-based treatment for chronic pain, and to examine change in these processes in relation to improvements in patient functioning. Individuals with chronic pain attending an interdisciplinary ACT-based rehabilitation program completed measures of pain, functioning, depression, pain acceptance, cognitive fusion, decentering, and committed action at pre- and post treatment and during a nine-month follow-up. Significant improvements were observed from pre- to post-treatment and pre-treatment to follow-up on each of the treatment outcome and process variables. Regression analyses indicated that change in psychological flexibility processes cumulatively explained 6-27 % of the variance in changes in functioning and depression over both assessment periods, even after controlling for changes in pain intensity. Further research is needed to maximize the effectiveness of ACT for chronic pain, and to determine whether larger improvements in the processes of psychological flexibility under study will produce better patient outcomes, as predicted by the psychological flexibility model. PMID- 27397935 TI - New Parents' Psychological Adjustment and Trajectories of Early Parental Involvement. AB - Trajectories of parental involvement time (engagement and child care) across 3, 6, and 9 months postpartum and associations with parents' own and their partners' psychological adjustment (dysphoria, anxiety, and empathic personal distress) were examined using a sample of dual-earner couples experiencing first-time parenthood (N = 182 couples). Using time diary measures that captured intensive parenting moments, hierarchical linear modeling analyses revealed that patterns of associations between psychological adjustment and parental involvement time depended on the parenting domain, aspect of psychological adjustment, and parent gender. Psychological adjustment difficulties tended to bias the 2-parent system toward a gendered pattern of "mother step in" and "father step out," as father involvement tended to decrease, and mother involvement either remained unchanged or increased, in response to their own and their partners' psychological adjustment difficulties. In contrast, few significant effects were found in models using parental involvement to predict psychological adjustment. PMID- 27397936 TI - Changes in behaviour drive inter-annual variability in the at-sea distribution of northern gannets. AB - The at-sea distribution of seabirds primarily depends on the distance from their breeding colony, and the abundance, distribution and predictability of their prey, which are subject to strong spatial and temporal variation. Many seabirds have developed flexible foraging strategies to deal with this variation, such as increasing their foraging effort or switching to more predictable, less energy dense, prey, in poor conditions. These responses may vary both within and between individuals, and understanding this variability is vital to predict the population-level impacts of spatially explicit environmental disturbances, such as offshore windfarms. We conducted a multi-year tracking study in order to investigate the inter-annual variation in the foraging behaviour and location of a population of northern gannets breeding on Alderney in the English Channel. To do so, we investigated the link between individual-level behaviour and population level behaviour. We found that a sample of gannets tracked in 2015 had longer trip durations, travelled further from the colony and had larger core foraging areas and home range areas than gannets tracked in previous years. This inter annual variation may be associated with oceanographic conditions indexed by the North Atlantic Oscillation (NAO). Our findings suggest that this inter-annual variation was driven by individuals visiting larger areas in all of their trips rather than individuals diversifying to visit more, distinct areas. These findings suggest that, for gannets at least, if prey becomes less abundant or more widely distributed, more individuals may be required to forage further from the colony, thus increasing their likelihood of encountering pressures from spatially explicit anthropogenic disturbances. PMID- 27397937 TI - Conversion and the Real: The (Im)Possibility of Testimonial Representation. AB - Although the spiritual vibration of conversion can be felt (by the curious outsider) through what conversion performers say in their testimonial discourse, what transforms the convert 'on stage' into a 'new being' and what is 'the real' (le reel) in conversion performance remain unclear. An important question in this connection is, What is 'real' in a conversion representation, both with respect to the convert's interaction with the audience and to the construction of social reality? Following Lacan's tripartite register of the imaginary, the symbolic, and the real, in this essay I argue that through testimonial discourse converts construct social reality as an answer to the impossibility of 'the real' in their performative discursive practice. In the first part, I question the constructed nature of testimonial representations-as well as some academic knowledge production that has governed conversion research in the last few decades-and how these representations encourage 'outsiders' to read the narrative repertoire as a negation or mirroring 'the real' of the conversion experience. In the second part, I apply Roland Barthes' analytic reflections on photography to conversion research, especially the notions of the studium (the common ground of cultural meanings) and the punctum (a personal experience that inspires private meaning). This brings me to a number of theorists (mostly never used in the field of religious conversion)-Jacques Lacan, Roland Barthes, and Slavoj Zizek-who are important to the perspective that is developed in this essay. PMID- 27397939 TI - Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics. AB - The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation. PMID- 27397938 TI - Heterocycle Formation via Palladium-Catalyzed C-H Functionalization. AB - Heterocyclic compounds are ubiquitous in natural products, pharmaceuticals, and agrochemicals. Therefore, the design of novel protocols to construct heterocycles more efficiently is a major area of focus in the organic chemistry. In the past several years, cyclization reactions based upon palladium-catalyzed C-H activation have received substantial attention due to their capacity for expediting heterocycle synthesis. This review discusses strategies for heterocycle synthesis via palladium-catalyzed C-H bond activation and highlights recent examples from the literature. PMID- 27397940 TI - A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile. AB - In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities. PMID- 27397941 TI - Grolar Bears, Social Class, and Policy Relevance: Extraordinary Agendas for the Emerging 21st Century. AB - This Agenda article first considers whether social psychology is in the best or worst of times and suggests that we are instead in extraordinary times, given exciting agendas and potential policy relevance, if we are careful. The article illustrates with two current research agendas-the hybrid vigor of multiple categories and the psychology of social class-that could inform policy. The essay then reflects on how we know when our work is indeed ready for the public arena. Regarding hybrids: World immigration, social media, and global businesses are increasing. How will this complicate people's stereotypes of each other? One agenda could build on the existing social and behavioral science of people as social hybrids, emerging with a framework to synthesize existing work and guide future research that better reflects our changing world. Policy implications already emerge from our current knowledge of hybrids. Regarding the social psychology of social class: We do not know enough yet to give advice, except to suggest questioning some common stereotypes, e.g., about the economic behavior of lower-income people. Before the budding social psychology of class can be ready for policy export, the research results need replication, validation, and generality. Overall, principles of exportable policy insights include peer reviewed standards, honest brokering, nonpartisan advice, and respectful, trustworthy communication. Social psychology can take advantage of its extraordinary times to be innovative and useful. PMID- 27397942 TI - A Review of Flood-Related Storage and Remobilization of Heavy Metal Pollutants in River Systems. AB - Recently observed rapid climate changes have focused the attention of researchers and river managers on the possible effects of increased flooding frequency on the mobilization and redistribution of historical pollutants within some river systems. This text summarizes regularities in the flood-related transport, channel-to-floodplain transfer, and storage and remobilization of heavy metals, which are the most persistent environmental pollutants in river systems. Metal dispersal processes are essentially much more variable in alluvia than in soils of non-inundated areas due to the effects of flood-sediment sorting and the mixing of pollutants with grains of different origins in a catchment, resulting in changes of one to two orders of magnitude in metal content over distances of centimetres. Furthermore, metal remobilization can be more intensive in alluvia than in soils as a result of bank erosion, prolonged floodplain inundation associated with reducing conditions alternating with oxygen-driven processes of dry periods and frequent water-table fluctuations, which affect the distribution of metals at low-lying strata. Moreover, metal storage and remobilization are controlled by river channelization, but their influence depends on the period and extent of the engineering works. Generally, artificial structures such as groynes, dams or cut-off channels performed before pollution periods favour the entrapment of polluted sediments, whereas the floodplains of lined river channels that adjust to new, post-channelization hydraulic conditions become a permanent sink for fine polluted sediments, which accumulate solely during overbank flows. Metal mobilization in such floodplains takes place only by slow leaching, and their sediments, which accrete at a moderate rate, are the best archives of the catchment pollution with heavy metals. PMID- 27397944 TI - Epistemic modesty, ostentatiousness and the uncertainties of epigenetics: on the knowledge machinery of (social) science. AB - Epigenetic processes are garnering attention in the social sciences, where some scholars assert their importance for theorizing social life. I engage with such ideas here by drawing on interviews with leading bioscientists. To begin with, I underscore the (productive) uncertainties of those working in and around epigenetics; I describe these as a manifestation of 'epistemic modesty', and suggest that dissensus helps to propel biomedical innovation. Then, drawing on the concept of 'alien science', I detail some researchers' ambivalences regarding the notion of 'transgenerational inheritance'; their dissatisfaction with the (public) communication practices of other scientists (situated in what I term a regime of 'epistemic ostentatiousness'); and the challenges faced when moderating societal discussion of epigenetics in ways that expand excitement whilst deflating (what researchers regard as) unrealistic expectations. The paper concludes with reflections on the knowledge machinery of the (social) sciences, and employs the study data to interrogate sociological engagements with epigenetics. PMID- 27397945 TI - Living well in the Neuropolis. AB - This paper is about the relationship between cities and brains: it charts the back-and-forth between the hectic, stressful lives of urban citizens, and a psychological and neurobiological literature that claims to make such stress both visible and knowable. But beyond such genealogical labour, the paper also asks: what can a sociology concerned with the effects of 'biosocial' agencies take from a scientific literature on the urban brain? What might sociology even contribute to that literature, in its turn? To investigate these possibilities, the paper centres on the emergence and description of what it calls 'the Neuropolis' - a term it deploys to hold together both an intellectual and scientific figure and a real, physical enclosure. The Neuropolis is an image of the city embedded in neuropsychological concepts and histories, but it also describes an embodied set of (sometimes pathological) relations and effects that take places between cities and the people who live in them. At the heart of the paper is an argument that finding a way to thread these phenomena together might open up new paths for thinking about 'good' life in the contemporary city. Pushing at this claim, the paper argues that mapping the relations, histories, spaces, and people held together by this term is a vital task for the future of urban sociology. PMID- 27397943 TI - Ligand-Accelerated ortho-C-H Olefination of Phenylacetic Acids. PMID- 27397946 TI - Sustaining Adoption of Science-based Prevention Through Communities That Care. PMID- 27397947 TI - Innovations in science and scenarios for assessment. AB - Scenarios for the Third National Climate Assessment (NCA3) were produced for physical climate and sea level rise with substantial input from disciplinary and regional experts. These scenarios underwent extensive review and were published as NOAA Technical Reports. For land use/cover and socioeconomic conditions, scenarios already developed by other agencies were specified for use in the NCA3. Efforts to enhance participatory scenario planning as an assessment activity were pursued, but with limited success. Issues and challenges included the timing of availability of scenarios, the need for guidance in use of scenarios, the need for approaches to nest information within multiple scales and sectors, engagement and collaboration of end users in scenario development, and development of integrated scenarios. Future assessments would benefit from an earlier start to scenarios development, the provision of training in addition to guidance documents, new and flexible approaches for nesting information, ongoing engagement and advice from both scientific and end user communities, and the development of consistent and integrated scenarios. PMID- 27397948 TI - Predicting large wildfires across western North America by modeling seasonal variation in soil water balance. AB - A lengthening of the fire season, coupled with higher temperatures, increases the probability of fires throughout much of western North America. Although regional variation in the frequency of fires is well established, attempts to predict the occurrence of fire at a spatial resolution <10 km2 have generally been unsuccessful. We hypothesized that predictions of fires might be improved if depletion of soil water reserves were coupled more directly to maximum leaf area index (LAImax) and stomatal behavior. In an earlier publication, we used LAImax and a process-based forest growth model to derive and map the maximum available soil water storage capacity (ASWmax) of forested lands in western North America at l km resolution. To map large fires, we used data products acquired from NASA's Moderate Resolution Imaging Spectroradiometers (MODIS) over the period 2000-2009. To establish general relationships that incorporate the major biophysical processes that control evaporation and transpiration as well as the flammability of live and dead trees, we constructed a decision tree model (DT). We analyzed seasonal variation in the relative availability of soil water (fASW) for the years 2001, 2004, and 2007, representing respectively, low, moderate, and high rankings of areas burned. For these selected years, the DT predicted where forest fires >1 km occurred and did not occur at ~100,000 randomly located pixels with an average accuracy of 69 %. Extended over the decade, the area predicted burnt varied by as much as 50 %. The DT identified four seasonal combinations, most of which included exhaustion of ASW during the summer as critical; two combinations involving antecedent conditions the previous spring or fall accounted for 86 % of the predicted fires. The approach introduced in this paper can help identify forested areas where management efforts to reduce fire hazards might prove most beneficial. PMID- 27397949 TI - Silicon epitaxy on H-terminated Si (100) surfaces at 250 degrees C. AB - Low temperature Si epitaxy has become increasingly important due to its critical role in the encapsulation and performance of buried nanoscale dopant devices. We demonstrate epitaxial growth up to nominally 25 nm, at 250 degrees C, with analysis at successive growth steps using STM and cross section TEM to reveal the nature and quality of the epitaxial growth. STM images indicate that growth morphology of both Si on Si and Si on H-terminated Si (H: Si) is epitaxial in nature at temperatures as low as 250 degrees C. For Si on Si growth at 250 degrees C, we show that the Si epitaxial growth front maintains a constant morphology after reaching a specific thickness threshold. Although the in-plane mobility of silicon is affected on the H: Si surface due to the presence of H atoms during initial sub-monolayer growth, STM images reveal long range order and demonstrate that growth proceeds by epitaxial island growth albeit with noticeable surface roughening. PMID- 27397950 TI - Conduit margin heating and deformation during the AD 1886 basaltic Plinian eruption at Tarawera volcano, New Zealand. AB - During explosive eruptions, a suspension of gas and pyroclasts rises rapidly within a conduit. Here, we have analysed textures preserved in the walls of a pyroclastic feeder dyke of the AD 1886 Tarawera basaltic Plinian fissure eruption. The samples examined consist of basaltic ash and scoria plastered onto a conduit wall of a coherent rhyolite dome and a welded rhyolitic dome breccia. We examine the textural evidence for the response of the wall material, built of ~75 vol.% glass and ~25 vol.% crystals (pore-free equivalent), to mass movement in the adjacent conduit. In the rhyolitic wall material, we quantify the orientation and aspect ratio of biotite crystals as strain markers of simple shear deformation, and interpret juxtaposed regions of vesiculation and vesicle collapse as evidence of conduit wall heating. Systematic changes occur close to the margin: (1) porosity is highly variable, with areas locally vesiculated or densified, (2) biotite crystals are oriented with their long axis parallel to the margin, (3) the biotites have greater aspect ratios close to the margin and (4) the biotite crystals are fractured. We interpret the biotite phenocryst deformation to result from crystal fracture, rotation and cleavage-parallel bookcase translation. These textural observations are inferred to indicate mechanical coupling between the hot gas-ash jet and the conduit wall and reheating of wall rock rhyolite. We couple these observations with a simple 1D conductive heating model to show what minimum temperature the conduit wall needs to reach in order to achieve a temperature above the glass transition throughout the texturally-defined deformed zone. We propose that conduit wall heating and resulting deformation influences conduit margin outgassing and may enhance the intensity of such large basaltic eruptions. PMID- 27397951 TI - Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: characterizing spectral interferences using inorganic mass spectrometry. AB - Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e.g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n=619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens. PMID- 27397952 TI - Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis. AB - BACKGROUND: Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. MATERIALS AND METHODS: Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. RESULTS: Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. CONCLUSION: A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test. PMID- 27397953 TI - An assessment of hand hygiene practices of healthcare workers of a semi-urban teaching hospital using the five moments of hand hygiene. AB - BACKGROUND: Hand hygiene has been described as the cornerstone and starting point in all infection control programs, with the hands of healthcare staff being the drivers and promoters of infection in critically ill patients. The objectives of this study were to access healthcare workers compliance with the World Health Organization (WHO) prescribed five moments of hand hygiene as it relates to patient care and to determine the various strata of healthcare workers who are in default of such prescribed practices. METHODS: The study was an observational, cross-sectional one. Hand hygiene compliance was monitored using the hand hygiene observation tool developed by the WHO. A nonidentified observer was used for monitoring compliance with hand hygiene. The observational period was over a 60 day period from August 2015 to October 2015. RESULTS: One hundred and seventy-six observations were recorded from healthcare personnel. The highest number of observations were seen in surgery, n = 40. The following were found to be in noncompliance before patient contact - anesthetist P = 0.00 and the Intensive Care Unit P = 0.00 while compliance was seen with senior nurses (certified registered nurse anesthetist [CRNA]) P = 0.04. Concerning hand hygiene after the removal of gloves, the following were areas of noncompliance - the emergency room P = 0.00, CRNA P = 0.00, dental P = 0.04, and compliance was seen with surgery P = 0.01. With regards to compliance after touching the patient, areas of noncompliance were the anesthetists P = 0.00, as opposed to CRNA P = 0.00, dental P = 0.00, and Medicine Department P = 0.02 that were compliant. Overall, the rates of compliance to hand hygiene were low. DISCUSSION: The findings however from our study show that the rates of compliance in our local center are still low. The reasons for this could include lack of an educational program on hand hygiene; unfortunately, healthcare workers in developing settings such as ours regard such programs as being mundane. CONCLUSION: The observance of hand hygiene is still low in our local environment. Handwashing practices in our study show that healthcare workers pay attention to hand hygiene when it appears there is a direct observable threat to their wellbeing. Educational programs need to be developed to address the issue of poor hand hygiene. PMID- 27397954 TI - Postoperative complications from primary repair of cleft lip and palate in a semi urban Nigerian teaching hospital. AB - BACKGROUND: This paper seeks to investigate the incidence of short-term postoperative complications in children and adult patients undergoing primary surgery of cleft lip and palate. PATIENTS AND METHODS: One hundred and fifteen patients consisting of children (below 12 years) and adult (12 years and above) who were operated for both cleft lip and palate within a 2-year period at the University of Maiduguri Teaching Hospital were reviewed postoperatively at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year intervals, respectively. The complications encountered within the periods of the review were recorded. RESULTS: One hundred and twenty surgeries were performed on 115 patients (85 children 30 Adults). A total of 43 complications (31 in children and 12 in adults) were recorded over the study period. Eighteen (41.9%) of these complications were noticed in unilateral cleft lip repair, while 12 (27.9%) and 13 (30.2%) complications were observed in bilateral cleft lip and cleft palate surgeries, respectively. A higher complication rate (72.0%) was recorded in children compared with adults. Major complications (13.9%) were, however, observed more in adults than children. CONCLUSION: Although every surgeon attempts to prevent complications during surgery, they may still occur. The high complication rate observed in our study may be due to a small sample size. General complications observed among children are due to cross infection during a hospital stay, contributing immensely to the higher rate of complications in children. Moreover, this may be reduced by short hospital stay following surgery. We also advocate early contact with children with cleft, and early surgical intervention in other to prevent some of the major complications encountered in adult patients. PMID- 27397955 TI - Effect of olive oil massage on weight gain in preterm infants: A randomized controlled clinical trial. AB - BACKGROUND: Despite the fact that effect of massage with or without oil on the baby's weight gain is not clear, but recent studies have shown that massage with essential oils make lipid absorption through the skin. The aim of this study was to evaluate the effect of olive oil massage on weight gain in preterm infants. MATERIALS AND METHODS: This study was a single-blind, randomized controlled clinical trial. In this study, infants who met inclusion criteria for the study were divided into two groups by using random numbers table. Newborns in intervention group were under massage for 10 days and 3 times for 15 min daily; the mother of these newborns had been trained already using olive oil. Moreover, the infants of the control group were under massaging without oil same as the above-mentioned method. Researchers weighed babies daily during 10 days and recorded it at the checklist. Data from the study were reviewed and analyzed by descriptive statistics and repeated measure test using the statistical software SPSS/13. RESULTS: This study showed that the neonatal weight gain in the infants with the oil massage was 21 g daily in average, whereas the increase in infant massage without oil was 7 g. This difference was statistically significant (P < 0.001). CONCLUSION: Considering the positive effect of infant massage on weight gain in premature infants with olive oil, it is recommended that nurses use oil in infant massage in the neonatal units. PMID- 27397956 TI - Childhood ovarian neoplasms in Ibadan, South-western Nigeria. AB - BACKGROUND: Childhood ovarian neoplasms are very rare. Little information is available on the relative pattern and frequency of these tumors in Nigerian children. Earlier study done in Ibadan involved ovarian neoplasms in children and adolescents. The aim of this study is to review cases of ovarian neoplasms in children <15 years over a 221/2 years period. MATERIALS AND METHODS: This was a retrospective study. Twenty-four cases of childhood ovarian neoplasms were seen in patients <15 years of age. These cases were classified using the current World Health Organization histological classification of ovarian tumors. RESULTS: Childhood ovarian neoplasms accounted for 2.8% of all cases of ovarian tumors seen in this period. Fourteen (58.3%) cases of childhood ovarian neoplasms were benign, and 10 (41.7%) were malignant. Mature cystic teratoma occurring in 13 (54.2%) was the most common childhood ovarian neoplasm and was most prevalent between 10 and 14 years of age. Burkitt lymphoma was the most common 4 (40%) malignant childhood ovarian tumor and prevalent between 5 and 14 years of age. CONCLUSION: Mature cystic teratoma remains the single most common childhood ovarian neoplasms, and Burkitt's lymphoma is the most malignant childhood ovarian tumor in Ibadan, South-western Nigeria. PMID- 27397957 TI - Environmental factors related to the occurrence of oral clefts in a Brazilian subpopulation. AB - BACKGROUND: A cross-sectional study was conducted at the Craniofacial Rehabilitation Center in the General Hospital of the University of Cuiaba, Cuiaba city, Mato Grosso, Brazil. MATERIALS AND METHODS: Poisson regression model was used to analyze the relationship between antenatal factors and the occurrence of oral clefts in 116 patients. RESULTS: Oral clefts were more common in males (64.66%) and White race (46.02%). The mean age of the children was 21.91 months. The most common type of cleft was cleft lip and palate (CLP, 55.17%). Maternal and paternal smoking in the first trimester of pregnancy and parity were significantly associated with the occurrence of CLP. Parent's age, educational level, and occupation did not interfere in the occurrence of oral clefts. There was also no significant association between maternal illness, medication use, alcohol consumption, and maternal exposure to chemicals in the first trimester of pregnancy and the occurrence of clefts in this population. CONCLUSION: The analysis of the environmental factors present during the pregnancy of children with oral clefts revealed a significant association between parity (second onward), maternal smoking, and paternal smoking and the occurrence of CL and/or palate in this population. PMID- 27397958 TI - Cycloplegic effect of atropine compared with cyclopentolate-tropicamide combination in children with hypermetropia. AB - BACKGROUND: Cycloplegic refraction is important in assessing children with hypermetropia. Atropine, though the gold standard cycloplegic agent for refraction in children, has a long duration of action and more severe side effects compared to short-acting cycloplegic agents. The aim of the study was to compare the cycloplegic effect of atropine with cyclopentolate and tropicamide combination in children with hypermetropia. SUBJECTS AND METHODS: This was a crossover interventional study in children with hypermetropia. Cycloplegic refraction using two separate regimens of cycloplegic drugs was done on all subjects. Data were analyzed using the statistical software SPSS version 22.0. The mean spherical equivalent values of regimen 1 (atropine 1%) and regimen 2 (cyclopentolate 1% and tropicamide 1%) were presented as mean and standard deviation. A P <= 0.05 was considered statistically significant. RESULTS: One hundred and twenty-six eyes of 63 subjects aged 5-12 years were examined. The mean spherical equivalent values for regimen 1 and regimen 2 for the right eyes were 4.73 +/- 2.1 DS and 4.54 +/- 1.9 DS, respectively (P = 0.59). The mean spherical equivalent values for regimens 1 and 2 for the left eyes were 4.74 +/- 2.0 DS and 4.54 +/- 1.8 DS, respectively (P = 0.56). CONCLUSION: The combination of 1% cyclopentolate and 1% tropicamide could be a useful alternative to atropine 1% for cycloplegic refraction in children with hypermetropia. PMID- 27397959 TI - An assessment of serum prolactin levels among infertile women with galactorrhea attending a gynecological clinic North-West Nigeria. AB - BACKGROUND: Galactorrhea is a common manifestation of hyperprolactinemia but may not always be present in women with hyperprolactinemia. This study was, therefore, undertaken to assess the serum prolactin levels of infertile women presenting with galactorrhea and to determine the prevalence of hyperprolactinemia among them. MATERIALS AND METHODS: This was a retrospective study of serum prolactin levels of 63 female partners of infertile couples attending the gynecological clinic of Federal Medical Centre, Birnin Kudu, Jigawa State, Nigeria, who were found to have galactorrhea from January 1, 2012, to December 31, 2013. Ethical clearance was obtained. Solid phase enzyme-linked immunosorbent assay was used to measure serum prolactin. Sociodemographic characteristics were determined. The data obtained were analyzed using SPSS version 17.0 statistical software. Absolute numbers and simple percentages were used to describe categorical variables. Similarly, quantitative variables were described using measures of central tendency (mean, median) and measures of dispersion (range, standard deviation) as appropriate. RESULTS: The average age of the women was 27.9 +/- 5.6 years. In half of the cases (50%), galactorrhea was associated with menstrual disturbances, mainly amenorrhea (23.3%). Although most (63.3%) of the clients had normal serum prolactin level despite being galactorrheic, averagely there was a marked elevation in serum prolactin of as high as 40.3 +/- 52.3 ng/mL. CONCLUSION: We conclude, therefore, that the prevalence of hyperprolactinemia in this study was low when compared with other studies and that galactorrhea does not always indicate raised serum prolactin levels. PMID- 27397960 TI - Serum copper and zinc levels in preeclamptic Nigerian women. AB - BACKGROUND: The exact etiology of preeclampsia remains unknown even though several studies have been done. Some studies have shown that supplementation of zinc (Zn) and copper could ameliorate the effects of preeclampsia while other studies did not establish the beneficial role of these elements in preeclampsia. The objective of this study was to compare the Zn and copper levels in the serum of Nigerian women with or without preeclampsia. MATERIALS AND METHODS: In this study, serum Zn and copper levels were determined using atomic absorption spectrometry in 54 patients and 48 healthy normotensive pregnant women. The mean, standard deviation, Student's t-test, and Pearson correlation were employed. RESULTS: Serum Zn was significantly lower in patients than controls (8.27 +/- 0.60 vs. 12.16 +/- 1.83 MUmol/l. P <0.001) (t-test). Serum copper was also significantly lower in patients than controls (8.14 +/- 1.80 vs. 16.62 +/- 3.17 MUmol/l, P < 0.001). CONCLUSION: There was a significant reduction in the levels of Zn and copper in patients with preeclampsia. Dietary supplementation of these trace elements may help to prevent preeclampsia. PMID- 27397961 TI - Chronic kidney disease in Nigeria: Late presentation is still the norm. AB - BACKGROUND: Chronic kidney disease (CKD) has become a public health problem in Nigeria. Efforts are being geared toward early diagnosis and prevention of CKD. This study involved the evaluation of the referral pattern and mode of presentation of CKD patients at first contact in a tertiary health institution. PATIENTS AND METHODS: Patients' records over an 18 month period were retrieved and the following information extracted: Sociodemographic data, referral hospital, mode of presentation, etiology of CKD, packed cell volume, blood pressure, and estimated glomerular filtration rate (GFR) at first presentation. RESULTS: There were 202 CKD patients with a male: female ratio of 1.7:1 and a mean age of 48.15 +/- 16.69 years. The median estimated GFR of the patients at presentation was 3.17 ml/min/1.73 m(2). The common etiologies of CKD were chronic glomerulonephritis, hypertension, diabetes mellitus, obstructive nephropathy in 69 (34.2%), 47 (23.3%), 38 (18.8%), and 21 (10.4%) respectively. Among these patients, 111 (55%) and 98 (48.6%) had moderate to severe hypertension and anemia, respectively, 173 (85.6%) presented in CKD Stage 5, 101 (50%) required urgent hemodialysis whereas 123 (60.9%) required in-hospital admission. Only (18) 9% of these CKD patients presented by self-referral while (103) 51% were referred from secondary and private health facilities. CONCLUSION: Most Nigerian CKD patients still present very late to nephrologists implying that the present preventive strategies have not yielded desired results. Early diagnosis and referral of CKD patients could be better achieved through regular education of the public and retraining of health workers especially those in primary and secondary health institutions. PMID- 27397962 TI - Effect of automated red cell exchanges on oxygen saturation on-air, blood parameters and length of hospitalization in sickle cell disease patients with acute chest syndrome. AB - BACKGROUND: Red cell exchanges (RCEs) lead to improvement in tissue oxygenation and reduction in inflammatory markers in sickle cell disease (SCD) patients who present with acute chest syndrome (ACS). The aim of this study is to evaluate the effects of automated-RCE (auto-RCE) on oxygen saturation (SpO2) on-air, blood counts, the time to correct the parameters and length of hospitalization after the exchange in SCD patients presenting with ACS. SUBJECTS AND METHODS: This was 2 years study involving five SCD patients; the time for SpO2 on air to increase to >=95% and chest symptoms to resolve, postprocedure, as well as the length of in-patient hospitalization was recorded. All data were entered into Statistical Package for Social Sciences Version 20.0 (SPSS Inc., Chicago, IL, USA) computer software for analyses. RESULTS: The study involved 4 (80%) hemoglobin (Hb) SS and 1 (20%) HbSC patients. The median time of SpO2 recovery was 24 h, ranging from 6 to 96 h. About 60% (3/5) of patients achieved optimal SpO2 within 24 h post-RCE, while discharge from intensive care unit was 24 h after auto-RCE in one patient. The Hb concentration was significantly higher, while the total white cell and absolute neutrophil counts were significantly lower at the time of resolution of symptoms, compared to before auto-RCE (P < 0.05). The average post auto-red cell transfusion symptoms duration was 105.6 (24-240) h while mean inpatient stay was 244.8 (144-456) h. CONCLUSION: Auto-RCE could reverse hypoxia in ACS within 24 h. PMID- 27397963 TI - Management of a blinding orbital apex cyst in a 14-year-old girl. AB - This study was conducted to highlight the diagnostic and management challenges of orbital apex lesions. It is a retrospective report of a 14-year-old female who presented with no perception of light vision in her left eye following a 1-year history of left unilateral axial proptosis. Her computed tomography scan revealed a mass surrounding the optic nerve which was reported to be an optic nerve glioma. She had lateral orbitotomy and a cystic mass was dissected and excised. Systemic steroids and antibiotics were administered. Visual recovery was achieved in the immediate postoperative period. At discharge, her visual acuity was counting finger in the left eye. Visual recovery in the orbital apex lesions is possible if the patient is diagnosed early and managed promptly but delayed presentation and diagnostic challenges could lead to irreversible blindness. PMID- 27397964 TI - Photo-Triggered Click Chemistry for Biological Applications. AB - In the last decade and a half, numerous bioorthogonal reactions have been developed with a goal to study biological processes in their native environment, i.e., in living cells and animals. Among them, the photo-triggered reactions offer several unique advantages including operational simplicity with the use of light rather than toxic metal catalysts and ligands, and exceptional spatiotemporal control through the application of an appropriate light source with pre-selected wavelength, light intensity and exposure time. While the photoinduced reactions have been studied extensively in materials research, e.g., on macromolecular surface, the adaptation of these reactions for chemical biology applications is still in its infancy. In this chapter, we review the recent efforts in the discovery and optimization the photo-triggered bioorthogonal reactions, with a focus on those that have shown broad utility in biological systems. We discuss in each cases the chemical and mechanistic background, the kinetics of the reactions and the biological applicability together with the limiting factors. PMID- 27397966 TI - From division of labor to the collective behavior of social insects. AB - 'Division of labor' is a misleading way to describe the organization of tasks in social insect colonies, because there is little evidence for persistent individual specialization in task. Instead, task allocation in social insects occurs through distributed processes whose advantages, such as resilience, differ from those of division of labor, which are mostly based on learning. The use of the phrase 'division of labor' persists for historical reasons, and tends to focus attention on differences among individuals in internal attributes. This focus distracts from the main questions of interest in current research, which require an understanding of how individuals interact with each other and their environments. These questions include how colony behavior is regulated, how the regulation of colony behavior develops over the lifetime of a colony, what are the sources of variation among colonies in the regulation of behavior, and how the collective regulation of colony behavior evolves. PMID- 27397965 TI - Parasites modulate within-colony activity and accelerate the temporal polyethism schedule of a social insect, the honey bee. AB - Task allocation in social insect colonies is generally organised into an age related division of labour, termed the temporal polyethism schedule, which may in part have evolved to reduce infection of the colony's brood by pests and pathogens. The temporal polyethism schedule is sensitive to colony perturbations that may lead to adaptive changes in task allocation, maintaining colony homeostasis. Though social insects can be infected by a range of parasites, little is known of how these parasites impact within-colony behaviour and the temporal polyethism schedule. We use honey bees (Apis mellifera) experimentally infected by two of their emerging pathogens, Deformed wing virus (DWV), which is relatively understudied concerning its behavioural impact on its host, and the exotic microsporidian Nosema ceranae. We examined parasite effects on host temporal polyethism and patterns of activity within the colony. We found that pathogens accelerated the temporal polyethism schedule, but without reducing host behavioural repertoire. Infected hosts exhibited increased hyperactivity, allocating more time to self-grooming and foraging-related tasks. The strength of behavioural alterations we observed was found to be pathogen specific; behavioural modifications were more pronounced in virus-treated hosts versus N. ceranae-treated hosts, with potential benefits for the colony in terms of reducing within-colony transmission. Investigating the effects of multiple pathogens on behavioural patterns of social insects could play a crucial role in understanding pathogen spread within a colony and their effects on colony social organisation. PMID- 27397967 TI - THE ETHICS OF OCCUPATIONAL HEALTH AND SAFETY IN TURKEY: RESPONSIBILITY AND CONSENT TO RISK. AB - Work-related diseases, injuries, risks and deaths are the issues that have been recently gaining importance especially in developing countries. The ethical dimensions of occupational health and safety have remained as relatively understudied areas. Concepts such as responsibility, consent, autonomy, paternalism, choice, and certain values or justifications that are used in medical ethics and bioethics are also applicable to occupational health and safety. This article examines the ethical issues of responsibility and consent to occupational risk. It will first define the concepts of consent and risk, and then different views on responsibility and consent to risk will be discussed. The article will also examine the responsibility of the society and government regarding these concepts. PMID- 27397968 TI - Uncovering effective strategies for hearing loss prevention. AB - Occupational health agencies, researchers and policy makers have recognized the need for evidence on the effectiveness of interventions designed to reduce or prevent workplace injuries and illnesses. While many workplaces comply with legal or obligatory requirements and implement recommended interventions, few publications exist documenting the effectiveness of these actions. Additionally, some workplaces have discovered through their own processes, novel ways to reduce the risk of injury. Peer-reviewed information on the effectiveness of the many strategies and approaches currently in use could help correct weaknesses, or further encourage their adoption and expansion. The evaluation of intervention effectiveness would certainly contribute to improved worker health and safety. This need is particularly relevant regarding noise exposure in the workplace and hearing loss prevention interventions. In a 2006 review of the U.S. National Institute for Occupational Safety and Health (NIOSH) Hearing Loss Research Program, the independent National Academies of Sciences recommended that NIOSH place greater emphasis on identifying the effectiveness of hearing loss prevention measures on the basis of outcomes that are as closely related as possible to reducing noise exposure and work related hearing loss (http://www.nap.edu/openbook.php?record_id=11721). NIOSH used two different approaches to address that recommendation: the first one was to conduct research, including broad systematic reviews on the effectiveness of interventions to prevent occupational noise-induced hearing loss. The second was to create an award program, the Safe-In-Sound Excellence in Hearing Loss Prevention AwardTM, to identify and honor excellent real-world examples of noise control and other hearing loss prevention practices and innovations. PMID- 27397969 TI - Morphosyntax in Poor Comprehenders. AB - Children described as poor comprehenders (PCs) have reading comprehension difficulties in spite of adequate word reading abilities. PCs are known to display weakness with semantics and higher-level aspects of oral language, but less is known about their grammatical skills, especially with regard to morphosyntax. The purpose of this study was to examine morphosyntax in fourth grade PCs and typically developing readers (TDs), using three experimental tasks involving finiteness marking. Participants also completed standardized, norm referenced assessments of phonological memory, vocabulary, and broader language skills. PCs displayed weakness relative to TDs on all three morphosyntax tasks and on every other assessment of oral language except phonological memory, as indexed by nonword repetition. These findings help to clarify the linguistic profile of PCs, suggesting that their language weaknesses include grammatical weaknesses that cannot be fully explained by semantic factors. Because finiteness markers are usually mastered prior to formal schooling in typical development, we call for future studies to examine whether assessments of morphosyntax could be used for the early identification of children at risk for future reading comprehension difficulty. PMID- 27397970 TI - Synthesis of Amino-ADT Provides Access to Hydrolytically Stable Amide-Coupled Hydrogen Sulfide Releasing Drug Targets. AB - As additional physiological functions of hydrogen sulfide (H2S) are discovered, developing practical methods for exogenous H2S delivery is important. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) functionalized with H2S releasing anethole dithiolethione (ADT-OH) through ester bonds are being investigated for their combined anti-inflammatory and antioxidant potential. The chemical robustness of the connection between drug and H2S-delivery components, however, is a key and controllable linkage in these compounds. Because esters are susceptible to hydrolysis, particularly under acidic conditions such as stomach acid in oral drug delivery applications, we report here a simple synthesis of amino-ADT (ADT-NH2 ) and provide conditions for successful ADT-NH2 derivatization with the drugs naproxen and valproic acid. Using UV-vis spectroscopy and HPLC analysis, we demonstrate that amide-functionalized ADT derivatives are significantly more resistant to hydrolysis than ester-functionalized ADT derivatives. PMID- 27397971 TI - A putative species complex in the Sea of Japan revealed by DNA sequence data: a study on Lottia cf. kogamogai (Gastropoda: Patellogastropoda). AB - A putative new limpet species (Patellogastropoda) from the Sea of Japan is revealed by molecular genetic analyses using the mitochondrial markers 16S rRNA and cytochrome c oxidase subunit I (CO1), as well as the DNA marker 18S rRNA. Our data indicate that the limpet, collected in the Peter the Great Bay (Russian Federation), is not, as its morphology suggests, the Japanese species Lottia kogamogai Sasaki and Okutani, 1994, and might also hint towards another putative species complex in the Sea of Japan. The different currents between the Far East Asian mainland (cold, subpolar jet running southwards) and the Japanese archipelago (warm, subtropical jet running northwards) are likely to act as a barrier that has a substantial influence on species distribution in these waters. Accordingly, our results indicate that it is about time for a revision of patellogastropod species with a reported distribution in Japanese and Far Eastern Russian waters by an integrative approach using molecular genetic and morphological characters. The species investigated herein is referred to as Lottia cf. kogamogai until it is morphologically re-examined and compared with primary type specimens of known species. PMID- 27397972 TI - Experimental approaches to studying cumulative cultural evolution. AB - In humans, cultural traditions often change in ways which increase efficiency and functionality. This process, widely referred to as cumulative cultural evolution, sees beneficial traits preferentially retained, and it is so pervasive that we may be inclined to take it for granted. However, directional change of this kind appears to distinguish human cultural traditions from behavioural traditions that have been documented in other animals. Cumulative culture is therefore attracting an increasing amount of attention within psychology, and researchers have begun to develop methods of studying this phenomenon under controlled conditions. These studies have now addressed a number of different questions, including which learning mechanisms may be implicated, and how the resulting behaviours may be influenced by factors such as population structure. The current article provides a synopsis of some of these studies, and highlights some of the unresolved issues in this field. PMID- 27397973 TI - Prevalence of parasitic infection in captive wild animals in Bir Moti Bagh mini zoo (Deer Park), Patiala, Punjab. AB - AIM: The study was conducted to know the prevalence of gastrointestinal parasites of captive wild animals at Bir Moti Bagh Mini Zoo (Deer Park), Patiala, Punjab. MATERIALS AND METHODS: A total of 31 fecal samples from eight species of captive animals including Civet cat (Viverra zibetha), Porcupine (Hystrix indica), Nilgai (Boselaphus tragocamelus), Spotted deer (Axis axis), Black buck (Antelope cervicapra), Sambar deer (Cervus unicolor), Hog deer (Axis porcinus), and Barking deer (Muntiacus muntjak) were screened using classical parasitological techniques including sedimentation and floatation technique. RESULTS: Out of 31 fecal samples examined, 20 were positive for parasitic ova/oocysts of different species indicating an overall prevalence of 68.0%. The six different types of parasites observed in the study included strongyle (67%), Strongyloides spp. (14%), coccidia (38%), Trichuris spp. (19%), ascarid (10%), and Capillaria spp. (10%). Strongyles were the most common parasites observed (67%) followed by coccidia (38%). Mixed helminth and protozoan infection were observed in 48% of animals. No cestode or trematodes were detected during the study. CONCLUSION: The high prevalence of gastrointestinal parasites without overt clinical signs of disease or mortality as observed in this study is suggestive of subclinical infection. The findings will help in formulating the appropriate deworming protocol for parasitic control in these captive animals. PMID- 27397974 TI - Economic effects of foot and mouth disease outbreaks along the cattle marketing chain in Uganda. AB - AIM: Disease outbreaks increase the cost of animal production; reduce milk and beef yield, cattle sales, farmers' incomes, and enterprise profitability. The study assessed the economic effects of foot and mouth disease (FMD) outbreaks along the cattle marketing chain in selected study districts in Uganda. MATERIALS AND METHODS: The study combined qualitative and quantitative study designs. Respondents were selected proportionally using simple random sampling from the sampling frame comprising of 224, 173, 291, and 185 farmers for Nakasongola, Nakaseke, Isingiro, and Rakai, respectively. Key informants were selected purposively. Data analysis combined descriptive, modeling, and regression analysis. Data on the socio-economic characteristics and how they influenced FMD outbreaks, cattle markets revenue losses, and the economic cost of the outbreaks were analyzed using descriptive measures including percentages, means, and frequencies. RESULTS: Farmers with small and medium herds incurred higher control costs, whereas large herds experienced the highest milk losses. Total income earned by the actors per month at the processing level reduced by 23%. In Isingiro, bulls and cows were salvage sold at 83% and 88% less market value, i.e., a loss of $196.1 and $1,552.9 in small and medium herds, respectively. CONCLUSION: All actors along the cattle marketing chain incur losses during FMD outbreaks, but smallholder farmers are most affected. Control and prevention of FMD should remain the responsibility of the government if Uganda is to achieve a disease-free status that is a prerequisite for free movement and operation of cattle markets throughout the year which will boost cattle marketing. PMID- 27397975 TI - Effect of dietary iodine on production of iodine enriched eggs. AB - AIM: Objective of this study was to investigate the effect of different levels of iodine supplementation on iodine content of eggs in laying hens. MATERIALS AND METHODS: In the experiment, 135 laying hens (White Leghorn) of 55 weeks age were randomly distributed to 5 dietary treatments; each group contained 27 laying hens distributed in three replicates of 9 birds each. Diet T1 was control basal layer diet without iodine enrichment in which iodine content (I2) was as per NRC recommendation. Basal diets were supplemented with calcium iodate (Ca (IO3)2) at 5, 10, 15 and 20 mg/kg in T2, T3, T4 and T5 groups, respectively. The iodine content in the calcium iodate is 65.21%, therefore, the diets T2, T3, T4 and T5 contained 3.25, 6.50, 9.75 and 13.0 ppm iodine, respectively. The laying hens were fed the respective experimental diets ad libitum during the experimental period of 10-week. The iodine content of egg yolk and albumen was analyzed at the end of 5(th) and 10(th) week of the experiment. Economics of feeding for the production of iodine enriched egg was calculated at the end of the experiment. RESULTS: Increasing iodine levels in diet of hens from 0.45 to 13.0 ppm significantly increased egg iodine concentration, the highest concentration of egg iodine was observed in the group fed diet supplemented with 13.0 ppm iodine followed by those fed 9.75, 6.50, 3.25 and 0.45 ppm iodine in diet. There was no significant difference in the iodine levels of unboiled versus boiled eggs. Therefore, the consumers are ensured to receive the optimal levels of iodine from boiled iodine-enriched eggs. Among different diets, minimum and significantly lower feeding cost (Rs. per dozen or per kg eggs) was noticed in hens allotted T3 diet (6.50 ppm I2). However, feeding cost of hens receiving 3.25 and 9.25 ppm I2 was statistically (p<0.05) similar to control group (T1). Further, it was noticed that feeding cost (Rs. per dozen or per kg eggs) was significantly increased due to the inclusion of higher level of iodine (13.0 ppm). CONCLUSION: It was concluded that supplementing iodine at 6.50 ppm in layers diet was economically better for the production of iodine enriched eggs followed by feed iodine supplementation at 3.25 ppm as compared to control and other treatment groups. PMID- 27397976 TI - Plasma progesterone profile and conception rate following exogenous supplementation of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone releasing intra-vaginal device in repeat-breeder crossbred cows. AB - AIM: This study was designed to evaluate the effect of gonadotropin-releasing hormone (GnRH), human chorionic gonadotropin (hCG), and progesterone impregnated intra-vaginal device on progesterone profile and conception rate in repeat breeding crossbred cows. MATERIALS AND METHODS: Repeat-breeding crossbred cows aged 3-8 years (n=32), lactating and negative to white side test were randomly divided into four groups: Group 1 (Control, n=8), Group 2 (GnRH at 10 ug i.m, n=8), Group 3 (hCG at 1500 IU i.m., n=8), and Group 4 (progesterone impregnated intra-vaginal device at 958 mg, n=8). All the treatme nts were given on 5(th) daypostbreeding and in Group 4 intra-vaginally implanted device was withdrawn on 9(th) day (i.e., implant inserted for total 4 days) of the estrous cycle. Blood samples were collected on day 0, 5, 10, 15, and day 20 of estrous cycle, and plasma was separated for progesterone estimation. RESULTS: Accessory corpus luteum was not formed in crossbred cows of Group4 and control group. However, total 6 and 8 accessory corpora lutea were found in Group 2 and Group 3, respectively. In pregnant cows, the plasma progesterone concentration increased continuously from day 0 to day 20. In non-pregnant cows, it increased from day 0 to day 15 and then declined. The conception rate on day 60 in Group 1, Group 2, Group 3, and Group 4 was 37.5%, 50%, 75%, and 37.5%, respectively. CONCLUSIONS: Treating repeat-breeder cows with hCG is effective in increasing conception rate by developing accessory corpora lutea and higher progesterone level. PMID- 27397977 TI - The types of endocrine cells in the pancreas of Sunda porcupine (Hystrix javanica). AB - AIM: To identify the types of endocrine cells in the pancreas of the Sunda porcupine (Hystrix javanica) and its immunolocalization. MATERIALS AND METHODS: Five adult H. javanica were used without sexual distinction. The presences of endocrine cells (glucagon, insulin, somatostatin, and pancreatic polypeptide [PP]) in pancreatic tissues were detected using the avidin-biotin-peroxidase complex method. RESULTS: The fusiform, round, and oval form endocrine cells were detected in the islets of Langerhans and exocrine parts. Most of the insulin cells were found in the central area, glucagon cells were identified in the central and peripheral areas, and somatostatin and PP cells were detected in the mantle area of the islets of Langerhans. Glucagon and somatostatin cells were also detected in smaller numbers of peripheral parts of the islet. In all of the islet parts, glucagon endocrine cells were most prevalent cell type and then, somatostatin, insulin, and PP. In the exocrine parts, PP, somatostatin, glucagon, and insulin endocrine cells were found in the inter-acinus part with moderate, moderate, a few and rare numbers, in that order. In the pancreatic duct, glucagon and somatostatin cells were found between epithelial cells in rare numbers. CONCLUSION: The pancreas of Sunda porcupine (H. javanica) contains four types of major pancreatic endocrine cells with approximately similar distribution patterns to the other rodents, except for abundant glucagon cells in the peripheral area of the islets of Langerhans. PMID- 27397978 TI - Assessment of immune response to a lyophilized peste-des-petits-ruminants virus vaccine in three different breeds of goats. AB - AIM: Immune response to a lyophilized peste-des-petits-ruminants virus (PPRV) vaccine was evaluated in three different breeds of goats. MATERIALS AND METHODS: Three breeds of goats consisting six number of animals in three groups, i.e., Group A (local Assam hill goat), Group B (cross-bred), and Group C (Beetal goats) were randomly selected for evaluating the immune response to a lyophilized PPRV vaccine. RESULTS: A higher rise in the overall mean serum antibody titer was observed in Group A (40.50+/-3.74) than in Group B (37.58+/-37.58) and Group C (35.90+/-3.29) during the study period. CONCLUSION: Initially, a negative PPRV specific serum antibody titer was recorded in all the groups at 0(th) day of vaccination. Serum antibody titer in the vaccinated goats started rising gradually from the 14(th) day post vaccination. Later higher rise in the overall mean serum antibody titer in Group A (local Assam hill goat) lead to the conclusion that higher serum antibody titer in local non-descript breed might be due to their better adaptation to the environmental condition. PMID- 27397979 TI - Diversity of Meq gene from clinical Marek's disease virus infection in Saudi Arabia. AB - AIM: The aim of this study was to demonstrate the genomic features of Meq gene of Marek's disease virus (MDV) recently circulating in Saudi Arabia (SA). MATERIALS AND METHODS: Two poultry flocks suffering from mortalities and visceral tumors were presented to the Veterinary Teaching Hospital, King Faisal University, SA. Subjected to different diagnostic procedures: Case history, clinical signs, and necropsy as well as polymerase chain reaction followed by Meq gene sequence analysis. RESULTS: Case history, clinical signs, and necropsy were suggestive of MDV infection. The Meq gene was successfully detected in liver and spleen of infected chickens. A 1062 bp band including the native Meq ORF in addition to a 939 bp of S-Meq (short isoform of Meq) were amplified from Saudi 01-13 and Saudi 02-13, respectively. The nucleotide and deduced amino acids sequences of the amplified Meq genes of both Saudi isolates showed distinct polymorphism when compared with the standard USA virulent isolates Md5 and GA. The sequence analysis of the S-Meq gene showed a 123 bp deletion representing 41 amino acids between two proline-rich areas without any frameshift. The Meq gene encoded four repeats of proline-rich repeats (PRRs sequences), whereas the S-Meq contains only two PRRs. Interestingly, the phylogenetic analysis revealed that both of SA MDV isolates are closely related to the MDV strains from Poland. CONCLUSION: The two MDV isolates contain several nucleotide polymorphisms resulting in distinct amino acid substitutions. It is suggested that migratory and wild birds, as well as world trading of poultry and its by-products, have a great contribution in the transmission of MDVs overseas. PMID- 27397980 TI - New insights on ill-thriftiness in early-weaned buffalo calves. AB - AIM: The present study was designed to: (1) Investigate the effect of weaning time on various metabolic indices and growth pattern in buffalo calves compared to cow calves under field condition and (2) Shed light on the potential relationship between early weaning, growth metabolites, and suboptimal growth (ill-thrift) in buffalo calves. MATERIALS AND METHODS: A total number of 18 neonatal calves of both sexes and species (cattle and buffalo) were included in the study. Animals were divided into three groups according to their age at weaning as following: Cow calves (n=8) weaned at 4.5 months, buffalo calves (n=6) weaned at 3.5 months (early-weaned), and buffalo calves (n=4) weaned at 5.5 months (late-weaned). Morphological traits, growth metabolites, and hormonal profile were measured at monthly interval over the period of the study and around the time of weaning (2 weeks pre- and post-weaning). RESULTS: The obtained results showed that the trend of growth pattern was significantly increased in a linear pattern in cow calves and late-weaned buffalo calves, whereas early-weaned buffalo calves showed sharp decline in their body weight (BW) post-weaning. By the end of the study, early-weaned buffalo calves showed the lowest BW gain (ill thrift). There is a positive association between the morphological traits and various growth metabolites and hormonal indices. A significant decrease (p<0.05) in the concentrations of growth hormones (insulin-like growth factor-1 [IGF-1] and insulin) and other metabolites were reported in early-weaned buffalo calves compared to other animals. There is no association between stress indices (cortisol level and neutrophil to lymphocyte ratio) and growth rate. CONCLUSION: Suboptimal growth rate (ill-thriftiness) is common in early-weaned buffalo calves and is attributed to low blood levels of growth metabolites, in particularly, IGF 1. In addition, the strong positive associations between concentrations of IGF-1 and morphological characters of growth suggest that IGF-1 is a reliable indicator for assessing metabolic status of individual calves. PMID- 27397981 TI - Effect of curing ingredients and vacuum packaging on the physico-chemical and storage quality of ready-to-eat Vawksa rep (smoked pork product) during refrigerated storage. AB - AIM: The present study was conducted for the development of ready-to-eat Vawksa rep (smoked pork product) and to study the synergistic effect of curing ingredients and vacuum packaging on the physico-chemical and storage quality during refrigerated storage at (4 degrees C+/-1 degrees C) for 15 days. MATERIALS AND METHODS: Four different batches of Vawksa rep samples were prepared, i.e., T 1 (uncured, first cooked at 121 degrees C for 15 min, and then smoked at 120 degrees C for 30 min), T-2 (uncured, cooked, and smoked simultaneously at 120 degrees C for 45 min), T-3 (cured, first cooked at 121 degrees C for 15 min, and then smoked at 120 degrees C for 30 min), and T-4 (cured, cooked, and smoked simultaneously at 120 degrees C for 45 min). RESULTS: Cooking yield was significantly higher (p<0.05) for the T-4. The pH of T-3 and T-4 samples was significantly higher (p<0.05) on day 15. The tyrosine value of all the samples increased significantly (p<0.05) among the different days of analysis. Thiobarbituric acid value was significantly (p<0.05) lower in T-3 sample both at the beginning and at the end of storage period. In microbiological profile, total plate count was lower in T-3 and T-4 than T-1 and T-2. However, Escherichia coli count was negative for T-3 and T-4 samples throughout the storage period. Among sensory attributes, T-3 and T-4 samples registered superior scores for color, flavor, texture, juiciness, and overall acceptability. CONCLUSION: Furthermore, Vawksa rep (smoked pork product) could be prepared easily with little technology up-gradation and with a negligible escalation of production cost. PMID- 27397982 TI - Test day variability in yield and composition of Surti and Mehsani buffaloes milk at day 15 and 60 postpartum. AB - AIM: To estimate individual test day variability in yield and composition of Surti and Mehsani buffaloes milk at day 15 and 60 postpartum (pp). MATERIALS AND METHODS: A total of 13 normally calved Surti and Mehsani buffaloes each maintained at Livestock Research Stations of Navsari and Sardarkrushinagar Dantiwada Agricultural Universities, respectively, were selected for the study. Milk sample was collected from each selected buffalo at day 15 and 60 pp to study milk yield and composition variability between these two breeds. Buffaloes were categorized for the ease of data analysis and comparisons into four groups, viz., S15 (Surti buffaloes 15(th) day pp), S60 (Surti buffaloes 60(th) day pp), M15 (Mehsani buffaloes 15(th) day pp), and M60 (Mehsani buffaloes 60(th) day pp). RESULTS: There were 37.20% and 25.03% significant (p<=0.05) increase in mean test day milk yield (TDMY) of S60 and M60 as compared to S15 and M15 groups, respectively. The mean TDMY of Mehsani buffalo was 99.19% and 81.53% significantly (p<=0.05) higher than Surti buffaloes at day 15 and 60 pp, respectively. The mean fat and protein corrected test day milk yield (FPCTDMY) of all the groups was found to be significantly different (p<=0.05) from each other. There was significant (p<=0.05) increase of 1.94 and 3.45 kg in mean FPCTDMY with the progression of lactation between day 15 and 60 pp in Surti and Mehsani buffaloes, respectively. Similarly, the mean FPCTDMY of Mehsani buffaloes were approximately double with 103.27% and 96.36% higher yield as compared to Surti buffaloes at day 15 and 60 pp, respectively. Among milk composition, significant differences were observed for solid not fat (SNF) and protein%, whereas fat and lactose% were steady among four groups. The only significant (p<=0.05) difference was observed for SNF in M60 group, which was 8.29%, 6.85%, and 10.70% higher as compared to S15, S60, and M15 groups, respectively. The mean protein% in milk of Mehsani buffaloes was 21.01% and 33.05% significantly (p<=0.05) higher than Surti buffaloes milk at day 15 and 60 pp, respectively. However, there was a significant difference in protein% observed with the advancement of lactation in Mehsani buffaloes, but it was not so in the case of Surti buffaloes. CONCLUSION: Major consistent finding of the present study reveals that milk yield and protein% of Mehsani buffalo was significantly higher than Surti buffalo at day 15 and 60 pp. PMID- 27397983 TI - Effect of egg yolk powder on freezability of Murrah buffalo (Bubalus bubalis) semen. AB - AIM: The aim of this study was to investigate the effect of commercial egg yolk powder as an alternative to fresh egg yolk on freezability of Murrah buffalo semen. MATERIALS AND METHODS: Semen samples (12) from 3 Murrah buffaloes (4 from each bull) with mass motility (>=3+) and total motility (70% and above) were utilized in this study. Immediately after collection, each sample was divided into four groups. Groups I was diluted up to 60*10(6) sperm/ml with tris extender containing 10% fresh egg yolk and Groups II, III, and IV were diluted up to 60*10(6) sperm/ml with tris extender containing 2%, 4%, and 6% egg yolk powder, respectively. Semen samples were processed and cryopreserved followed by examination of frozen semen samples after 24 h. Semen samples from each group were evaluated for total motility, viability, acrosomal integrity, abnormality, and hypo-osmotic swelling test (HOST) response after dilution, pre-freeze, and post-thaw stage. RESULTS: Pre-freeze total motility was significantly (p<0.05) higher in Groups III and IV as compared to Groups I and II, and post-thaw total motility was significantly (p<0.01) higher in Group III as compared to other three groups. Viability was significantly (p<0.05) higher in Groups II, III, and IV than Group I at the pre-freeze stage. Significantly (p<0.01) higher viability and acrosomal integrity were recorded in Group III as compared to other three groups at the post-thaw stage. Abnormality was significantly (p<0.05) higher in Group IV than other three groups. HOST response was significantly (p<0.05) higher in Groups II and III than Groups I and IV at the pre-freeze and post-thaw stages. CONCLUSION: Addition of egg yolk powder at 4% level yielded significantly better results in terms of post-thaw semen quality as compared to the fresh egg yolk and other concentrations of egg yolk powder (2% and 6%). PMID- 27397984 TI - Human umbilical mesenchymal stem cells conditioned medium promote primary wound healing regeneration. AB - AIM: This research was conducted to clarify the capability of human umbilical mesenchymal stem cells conditioned medium (HU-MSCM) to promote regenerations of primary wound healing on the incision skin injury. MATERIALS AND METHODS: In this study, two approaches in vitro and in vivo already done. On in vitro analysis, tube formation was performed using HU vein endothelial cells in the presence of HU-MSCM, in some experiments cells line was incubated prior the presence of lipopolysaccharide and HU-MSCM then apoptosis assay was performed. Furthermore, in vivo experiments 12 female rats (Rattus norvegicus) were used after rats anesthetized, 7 mm wound was made by incision on the left side of the body. The wound was treated with HU-MSCM containing cream, povidone iodine was run as a control. Wound healing regenerations on the skin samples were visualized by hematoxylin-eosin staining. RESULTS: In vitro models elucidate HU-MSCM may decreasing inflammation at the beginning of wound healing, promote cell migration and angiogenesis. In addition in vivo models show that the incision length on the skin is decreasing and more smaller, HE staining describe decreasing of inflammation phase, increasing of angiogenesis, accelerate fibroplasia, and maturation phase. CONCLUSIONS: Taken together our observation indicates that HU MSCM could promote the acceleration of skin tissue regenerations in primary wound healing process. PMID- 27397985 TI - Evaluation of optimum roughage to concentrate ratio in maize stover based complete rations for efficient microbial biomass production using in vitro gas production technique. AB - AIM: A study was undertaken to evaluate the optimum roughage to concentrate ratio in maize stover (MS) based complete diets for efficient microbial biomass production (EMBP) using in vitro gas production technique. MATERIALS AND METHODS: MS based complete diets with roughage to concentrate ratio of 100:0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, and 30:70 were formulated, and 200 mg of oven dried sample was incubated in water bath at 39 degrees C along with media (rumen liquor [RL] - buffer) in in vitro gas syringes to evaluate the gas production. The gas produced was recorded at 8 and 24 h of incubation. In vitro organic matter digestibility (IVOMD), metabolizable energy (ME), truly digestible organic matter (TDOM), partitioning factor (PF), and EMBP were calculated using appropriate formulae. Ammonia nitrogen and total volatile fatty acids (TVFAs) production were analyzed in RL fluid-media mixture after 24 h of incubation. RESULTS: In vitro gas production (ml) at 24 h incubation, IVOMD, ME, TDOM, TVFA concentration, and ammonia nitrogen production were increased (p<0.01) in proportion to the increase in the level of concentrate in the diet. Significantly (p<0.01) higher PF and EMBP was noticed in total mixed ration with roughage to concentrate ratio of 60:40 and 50:50 followed by 70:30 and 40:60. CONCLUSION: Based on the results, it was concluded that the MS can be included in complete rations for ruminants at the level of 50-60% for better microbial biomass synthesis which in turn influences the performance of growing sheep. PMID- 27397986 TI - Effect of acute exposure to nonylphenol on biochemical, hormonal, and hematological parameters and muscle tissues residues of Nile tilapia; Oreochromis niloticus. AB - AIM: This study was aimed to evaluate some biochemical, hormonal, hematological, and histopathological changes in Nile tilapia, Oreochromis niloticus, after acute exposure to nonylphenol (NP). In addition to detection of NP residues in the fish, muscle tissues for human health concern. MATERIALS AND METHODS: A total of 90 apparently healthy Nile tilapia, O. niloticus, were randomly divided into three equal groups; each containing 30 fish (three replicates). Groups 1 and 2 kept as a control and solvent control (acetone), respectively, and Group 3 exposed to NP at a dose level of 500 ug/L water for 7 successive days. Blood and tissue samples were collected 2 times randomly from each group after 7 days from fish exposure to NP and 10 days from exposure stopping. RESULTS: Fish exposed to NP Group 3 showed anorexia, sluggish movement, erythema of the skin, areas of scales loss, and hemorrhagic ulcers in some areas of body region leading to exposing the viscera. Biochemical results revealed a significant increase in serum total proteins and globulins levels, a highly significant increase in serum alanine aminotransferase and aspartate aminotransferase activities, triglycerides, cholesterol, and creatinine levels, insignificant increase in serum uric acid level, and a highly significant decrease in serum testosterone and estradiol-beta17 levels in Group 3 in compare with the control group. Histopathological finding confirms these results. While hematological results of the same group revealed a significant increase in red blood cells count and packed cell volume value, insignificant increase in hemoglobin concentration, leukopenia, lymphopenia, and monocytopenia in compared with the control group. All of these changes appeared after 7 days from fish exposure to NP. Most of these alterations returned toward the normal level after 10 days from stopping exposure to NP. NP residues detected in fish muscle tissues of Group 3 during exposure and after stopping exposure to it. CONCLUSION: It is concluded that NP is a toxic pollutant and has an adverse effect on fish health and reproduction as well as accumulates in fish muscle tissues which may cause human health hazard. PMID- 27397987 TI - Characterization of promoter sequence of toll-like receptor genes in Vechur cattle. AB - AIM: To analyze the promoter sequence of toll-like receptor (TLR) genes in Vechur cattle, an indigenous breed of Kerala with the sequence of Bos taurus and access the differences that could be attributed to innate immune responses against bovine mastitis. MATERIALS AND METHODS: Blood samples were collected from Jugular vein of Vechur cattle, maintained at Vechur cattle conservation center of Kerala Veterinary and Animal Sciences University, using an acid-citrate-dextrose anticoagulant. The genomic DNA was extracted, and polymerase chain reaction was carried out to amplify the promoter region of TLRs. The amplified product of TLR2, 4, and 9 promoter regions was sequenced by Sanger enzymatic DNA sequencing technique. RESULTS: The sequence of promoter region of TLR2 of Vechur cattle with the B. taurus sequence present in GenBank showed 98% similarity and revealed variants for four sequence motifs. The sequence of the promoter region of TLR4 of Vechur cattle revealed 99% similarity with that of B. taurus sequence but not reveals significant variant in motifregions. However, two heterozygous loci were observed from the chromatogram. Promoter sequence of TLR9 gene also showed 99% similarity to B. taurus sequence and revealed variants for four sequence motifs. CONCLUSION: The results of this study indicate that significant variation in the promoter of TLR2 and 9 genes in Vechur cattle breed and may potentially link the influence the innate immunity response against mastitis diseases. PMID- 27397988 TI - Prevalence, type, and prognosis of ocular lesions in shelter and owned-client dogs naturally infected by Leishmania infantum. AB - AIM: The point prevalence of ocular lesions due to leishmaniasis was evaluated in 127 dogs living in a municipal shelter placed in a highly endemic area (Sicily, Italy). Moreover, the period prevalence, the type, and prognosis of lesions due to leishmaniasis were evaluated in 132 dogs with ocular pathologies referred to a Veterinary Teaching Hospital (VTH) in the same endemic area over a 3-year period. MATERIALS AND METHODS: All the dogs were submitted to ophthalmological examination. The diagnosis of leishmaniasis was made by cytological, serological (immune-fluorescent antibody test), and molecular (quantitative polymerase chain reaction) tests. RESULTS: The point prevalence of ocular lesions in 45 shelter dogs with leishmaniasis was 71.11% (45/127 dogs). The most frequent ocular lesion was blepharitis (50%) while anterior uveitis was observed in only 9.37% of cases. The period prevalence of ocular lesions due to leishmaniasis in the VTH group was 36.36% (48/132 dogs). In both groups, most of the lesions were bilateral and involved the anterior segment. Anterior uveitis was the most frequent ophthalmic finding in client-owned dogs (37.50%), but it occurred in only 9.37% of the shelter dogs. Keratouveitis often occurred during or after antiprotozoal treatment (14.58%; 7/48). In this study, the healing of eye injury following systemic antiprotozoal treatment was recorded in about half of cases (48%; 12/25 dogs), in which follow-up was possible. In more than 1/3 of cases (36%; 9/25), there was an improvement, but it was necessary to associate a long-term topical treatment; most of them, as well as those who had not responded to systemic therapy (16%; 4/25), had anterior uveitis or keratoconjunctivitis sicca. CONCLUSIONS: Ocular manifestations involve up to 2/3 of animals affected by canine leishmaniasis and lesions account for over 1/3 of ophthalmic pathologies observed at a referral clinic in an endemic area. The occurrence of anterior uveitis is more frequent in client-owned dogs than in shelter dogs. The onset of keratouveitis during or after antiprotozoal treatment could be attributed to the treatment or to a recurrence of the systemic form. The post-treatment uveal immune reaction, already observed in humans, could explain the difference in the frequency of keratouveitis between client-owned and shelter dogs, which have never been treated. PMID- 27397989 TI - Immunotoxicological, biochemical, and histopathological studies on Roundup and Stomp herbicides in Nile catfish (Clarias gariepinus). AB - AIM: The current study was directed to investigate the immunotoxic and oxidative stress effects of Roundup and Stomp herbicides and their combination on Nile catfish (Clarias gariepinus). MATERIALS AND METHODS: The experiment was carried out on 120 fish that randomly divided into four equal groups with three replicates: The first group kept as control, the second group exposed to 1/2 96 h lethal concentration 50 (LC50) of Roundup, the third group exposed to 1/2 96 h LC50 of Stomp, and the fourth one exposed to a combination of Roundup and Stomp at previously-mentioned doses. The experiment was terminated after 15 days; blood samples were obtained at 1(st), 8(th), and 15(th) days of treatment where the sera were separated for estimation of antioxidant enzymes. Meanwhile, at 15(th) day of exposure part of blood was collected from all groups with an anticoagulant for evaluation of phagocytic activity, then the fish were sacrificed, and specimens from the liver of all groups were obtained for histopathological examination. RESULTS: Our results indicated that both herbicides either individually or in combination elucidated significant decrease in phagocytic activity that was highly marked in group exposed to both herbicides. Furthermore, our data elicited an obvious elevation in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Meanwhile, the data depicted reduction in levels of reduced glutathione (GSH) and glutathione-S transferase (GST). Histopathological investigation of liver proved the aforementioned results. CONCLUSION: It could be concluded that either Roundup or Stomp alone cause significant deleterious effects on aquatic vertebrates. However, the use of their combination enhanced their toxic effects. Toxicity can end up in humans through the food chain. PMID- 27397990 TI - Optimization of dry period in Karan Fries cow. AB - AIM: The objective of this study was to optimize dry period (DP) length that can maximize the production across adjacent lactations and overall lifetime yield. MATERIALS AND METHODS: Performance records with respect to DP spread over a period of 15-year in Karan Fries (KF) cattle maintained at Livestock Research Centre (National Dairy Research Institute), were collected for the study. Data of 681 KF cows were analyzed by least square technique to examine the effect of non genetic factors on DP. Season of calving was classified into four seasons: Winter season (December-March), summer season (April-June), rainy season (July September), and autumn season (October-November); period of calving into five periods: 1998-2000 (1-period), 2001-2003 (II-period), 2004-2006 (III-period), 2007-2009 (IV-period), and 2010-2012 (V-period), and parity into six parities, i.e., 1(st), 2(nd), 3(rd), 4(th), 5(th), and >6(th) parities to see the effect of non-genetic factors on DP. RESULTS: Period of calving, season of calving, and parity did not affect the DP significantly (p<0.05). The overall least square mean of DP was 67.93+/-2.12 days. For the optimization of DP with regard to milk productivity, analysis was carried out by class interval method. DP was classified into eight classes (<22, 23-45, 46-67, 68-89, 90-111, 112-133, 134 155, and >156 days), and optimum level was obtained at 46-67 days (3(rd) class) with the following respective milk yield (MY) of 305 daily MY (4016.44+/-43.68 kg), total MY (4704.21+/-61.51 kg), MY per day of lactation length (13.03+/-0.13 kg), and MY per day of calving interval (11.68+/-0.41 kg). CONCLUSION: From the study, it was concluded that this optimal DP length (46-67 days) is suitable for maximizing the production. Hence, one should aim to dry off pregnant cows to achieve a DP of appropriate length to enhance productivity in the next lactation, as very short and very long DP reduces the economic profitability in dairy animals. PMID- 27397991 TI - Prevalence of coccidiosis among village and exotic breed of chickens in Maiduguri, Nigeria. AB - AIM: Coccidiosis is an important enteric parasitic disease of poultry associated with significant economic losses to poultry farmers worldwide. This survey was conducted from June 2014 through July 2015 with the main goal of investigating the prevalence and associated risk factors of coccidiosis among village and exotic breeds of chickens in Maiduguri, Northeastern Nigeria. MATERIALS AND METHODS: A total of 600 fecal samples from live and slaughtered birds comprising 284 young, 141, growers and 175 adult birds; 379 male and 221 female birds; 450 exotic and 150 local breeds of birds were randomly collected either as bird's fresh droppings or cutting open an eviscerated intestine of slaughtered birds, while noting their age, sex, and breeds. Samples were analyzed using standard parasitological methods and techniques. RESULTS: An overall prevalence rate of 31.8% (95% confidence interval: 28.07-35.52) was obtained. Higher prevalence rates were recorded in growing birds 58.9% (50.78-67.02), female birds 35.3% (29.00-41.60), exotic birds 42.4% (37.83-46.97), and broiler birds 68.7% (61.28 76.12). Similarly, higher infection rates were also observed among birds sampled from Mairi ward 66.7% (56.03-77.37), intensive management system 46.5% (41.61 51.39), and constructed local cages 54.0% (46.02-61.98). The difference in prevalence of coccidiosis among age groups, breeds, among exotic breeds, sampling sites, husbandry management systems, and litter management systems was statistically significant (<0.0001). However, no significant difference (p>0.05) of infection rates was observed in sex. CONCLUSION: Coccidiosis is endemic in both commercial and backyard poultry farms in Maiduguri due to poor management practices encouraging Eimeria oocysts build-up. It is therefore, recommended that poultry farmers should practice strict biosecurity measures on their farms, creating awareness on the prevalence of coccidiosis, routine vaccination against coccidiosis and educating poultry farmers on the need for maintaining good hygienic standards and good flock health management. PMID- 27397992 TI - The detrimental effects of lead on human and animal health. AB - Lead, a chemical element in the carbon group with symbol Pb (from Latin: Plumbum, meaning "the liquid silver") and has an atomic number 82 in the periodic table. It was the first element that was characterized by its kind of toxicity. In animal systems, lead (Pb) has been incriminated in a wide spectrum of toxic effects and it is considered one of the persistent ubiquitous heavy metals. Being exposed to this metal could lead to the change of testicular functions in human beings as well as in the wildlife. The lead poising is a real threat to the public health, especially in the developing countries. Accordingly, great efforts on the part of the occupational and public health have been taken to curb the dangers of this metal. Hematopoietic, renal, reproductive, and central nervous system are among the parts of the human body and systems that are vulnerable toward the dangers following exposure to high level of Pb. In this review, we discussed the massive harmful impact that leads acetate toxicity has on the animals and the worrying fact that this harmful toxicant can be found quite easily in the environment and abundance. Highlighting its (Pb) effects on various organs in the biological systems, its economic, as well as scientific importance, with the view to educate the public/professionals who work in this area. In this study, we focus on the current studies and research related to lead toxicity in animals and also to a certain extent toward human as well. PMID- 27397993 TI - Genetic analysis of first lactation production traits in Kankrej cattle. AB - AIM: The aim was to estimate genetic factors affecting the first lactation milk production traits in Kankrej cattle of North Gujarat. MATERIALS AND METHODS: The 475 first lactation records of Kankrej cows that were maintained at the Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Gujarat, over a period of 35 years from 1980 to 2014 were studied. The least squares maximum likelihood program was used to estimate genetic parameters of first lactation traits. Heritability was estimated through paternal half-sib analysis in adjusted data. RESULTS: The heritability estimate for production traits was 0.40+/-0.17, 0.45+/-0.17, 0.35+/-0.18, and 0.20+/-0.14 for standard 300 days milk yield (F300Y), total lactation milk yield (FLY), wet average (FWA), and lactation length (FLL), respectively, in the first parity. All the genetic and phenotypic correlations among different production efficiency traits were high and positive. Genetic correlations between F300Y and FLY, FLL, and FWA were 0.80+/-0.20, 0.59+/-0.16, and 0.81+/-0.32, where as the phenotypic correlations were 0.969, 0.688, and 0.868, respectively. Genetic correlations of FLY with FLL and FWA were 0.60+/-0.13 and 0.79+/-0.20, whereas the phenotypic correlations were 0.777 and 0.817, respectively. Genetic and phenotypic correlation between FLL and FWA was 0.63+/-0.28 and 0.31, respectively. CONCLUSION: The heritability estimate of all first parity lactation traits waslow to medium (0.20-0.45) indicated the scope for further improvement in this trait through selection as well as managemental practice. Higher genetic and phenotypic correlation between thefirst lactation milk production traits gives theidea that genetic gain due to selection for one trait also givesmorecorrelated response of selection for other traits which is economically advantageous. PMID- 27397995 TI - Cues for Cure; From within. PMID- 27397994 TI - Molecular characterization of exon 3 of caprine myostatin gene in Marwari goat. AB - AIM: To estimate genetic variability in exon 3 of caprine myostatin gene in Marwari goats. MATERIALS AND METHODS: A total of 120 blood samples from unrelated Marwari goats were randomly collected from different villages of Bikaner (Rajasthan), India. Genomic DNA was extracted from whole blood using blood DNA isolation kit (Himedia Ltd.) as per manufacturer's protocol. The quality of extracted genomic DNA was checked on 0.8% agarose gel. Specifically designed a primer set for caprine myostatin (MSTN) gene (Genebank accession no. DQ167575) was used to amplify the exon 3 region of MSTN gene in Marwari goat. The genetic variability in exon 3 of MSTN gene in Marwari goat was assessed on 8% polyacrylamide gel electrophoresis to detect single strand conformation polymorphism (SSCP) pattern. RESULTS: The exon 3 of MSTN gene in Marwari goat showed two types of conformation patterns on 8% polyacrylamide gel. One of the patterns showed only two bands and was considered as genotype AA, whereas another pattern having an extra band was designated as genotype AB. The frequencies of AA and AB genotype for exon 3 region of MSTN gene were calculated as 0.90 and 0.10, respectively. CONCLUSION: Low level of polymorphism was observed at exon 3 region of MSTN gene in Marwari goat through SSCP analysis. This information could be utilized in future breeding plan to exploit the unique characteristics of Marwari goat of Rajasthan. PMID- 27397996 TI - In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release. AB - INTRODUCTION: The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. METHODS: Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. RESULTS: A similar concentration of thrombin was observed in serum, L PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. CONCLUSIONS: The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension. PMID- 27397997 TI - Oct4B, CD90, and CD73 are upregulated in bladder tissue following electro resection of the bladder. AB - AIM: We tested the hypothesis that stimulation by electro-resection of bladder tissue induces stem cells in the tissue repair process. MATERIALS & METHODS: After primary transurethral resection of a bladder tumor and surrounding tissue (TUR-Bt), second TUR-Bt was performed. Tissues excised by second TUR-Bt were immunohistochemically stained for Oct4, a marker of pluripotency, and for CD90 and CD73, markers of mesenchymal stromal cells, when no bladder tumor cells remained. RESULTS AND CONCLUSIONS: Oct4B protein was sporadically stained in the cytoplasm of interstitial cells in four out of eight cases. CD90 and CD73 are upregulated in interstitial and vascular endothelial cells without CD45 expression. Mesenchymal stromal cells, but not pluripotent stem cells, may be mainly involved in bladder tissue repair. PMID- 27397998 TI - Epigallocatechin Gallate Inhibits Mouse Mesenchymal Stem Cell Differentiation to Adipogenic Lineage. AB - Epigallocatechin gallate (EGCG) is a major component of green tea polyphenols having a potent anti-oxidant potential. Besides inhibiting the growth of many cancer cell types and inducing proliferation and differentiation in keratinocytes, it has been shown to promote reduction of body fat. The fact that mesenchymal stem cells (MSCs) have ability to self-renew and differentiate into the cells of mesodermal lineages, such as fat and bone, it is, thus, possible that EGCG may directly be involved in affecting fat metabolism through its effect on mesenchymal stem cells. Hence, with this aim, the present study was designed to determine the effect of EGCG on mouse mesenchymal stem cells, C3H10T1/2 cells differentiation into adipocytes. To understand this process, the cells were incubated with varying concentrations of EGCG (1 MUM, 5 MUM, 10 MUM, 50 MUM) in the presence and /or absence of adipogenic medium for 9 days. The results demonstrated that, EGCG inhibited the cells proliferation, migration and also prevented their differentiation to adipogenic lineage. These effects were analyzed through the inhibition of wound healing activity, reduction in Oil red O stained cells, together with decrease in the expression of Adipisin gene following EGCG treatment. These observations thus demonstrated anti-adipogenic effect of EGCG with a possibility of its role in the therapeutic intervention of obesity. PMID- 27397999 TI - The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury. AB - Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration. PMID- 27398000 TI - Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats. AB - BACKGROUND/AIMS: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system of both acute and chronic renal changes. METHODS: This study used eighty Sprague-Dawley (SD) rats weighing 250-300g. They were assigned into four equal groups (each group n=20): (I) Negative control group, rats injected with single dose of 1 ml normal saline. (II) Positive control cisplatin, rats injected with a single dose of 5 mg/kg I.P in 1 ml saline. (III) Cisplatin and culture media group, rats injected with 0.5 ml of culture media single dose into the tail vein and (IV) Cisplatin and ADMSCs group, rats injected with a single dose of 0.5 ml of culture media containing 5 x10(6)ADMSCs into the tail vein one day after cisplatin administration. Each main group was further divided according to the timing of sacrifice into four subgroups (each subgroup n=5). Rats in the subgroup A were sacrificed after 4 days; subgroup B were sacrificed after 7 days; subgroup C were sacrificed after 11 days; and subgroup D were sacrificed after 30 days. Before sacrifice, 24 hrs.-urine was collected using a metabolic cage. Renal function was evaluated through blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Kidney tissue homogenate oxidative stress parameters, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione (GSH) were determined. In addition, histopathological analysis for active injury, regenerative and chronic changes was performed. RESULTS: ADMSCs were characterized and their capability of differentiation was proved. Cisplatin induced a significant increase in plasma creatinine and tissue MDA and induced a decrease in SOD, GSH and creatinine clearance. ADMSCs attenuated these changes. Cisplatin resulted in prominent histopathological changes in the term of tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. ADMSCs significantly lowered the injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4 and limited fibrotic score at day 30. CONCLUSION: ADMSCs have both protective and regenerative abilities with consequent limitation of the development of renal fibrosis after the cisplatin induced acute tubular necrosis, largely through an anti-oxidative activity. PMID- 27398001 TI - Stem Cells Therapy in Multiple Sclerosis - A New Hope for Progressive Forms. AB - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and represents a major cause of disability in young adults. Nowadays, the dichotomy between demyelination and neurodegeneration has been challenged, and both processes are believed to occur independently early in the disease process. 'Relapsing-remitting' MS is the most common subtype which generally shifts to a 'secondary progressive' form; MS progression is usually accompanied by a worsening of the motor, cognitive and emotional symptoms, as well as an increase in the disability level. Primary progressive MS represents a third subtype with severe disability scores, poor prognosis, and usually symptomatic management. In this perspective, an ideal therapy should have immunomodulatory, neuroprotective, regenerative and remyelinating potentials. Here, we discuss the promising abilities of stem cells therapies in patients with MS. The available data are tackled aiming to overcome the previously faced limitations and pave the way for larger scale randomized and controlled studies. PMID- 27398002 TI - Shifting Trends in Cutaneous and Aesthetic Surgery: A Need for Caution and Regulation. PMID- 27398003 TI - Periocular Aesthetics: An Emerging Era. PMID- 27398004 TI - Hills and Valleys: Understanding the Under-Eye. AB - Soft tissue deflation and descent have long been implicated in the pathogenesis of facial aging. In the periorbital area, the upper orbital region is thought to change by descent of the eyebrow, as well as deflation of brow fat. While the understanding of the aging changes in the upper eyelid region are relatively simple, the lower eyelid poses a myriad of aging changes, each demanding a specific management plan. These can be best described in terms of elevations, or 'Hills' and hollows, or 'Valleys'. This article simplifies the understanding of the lower eyelid in the light of anatomical knowledge, and available literature. It forms a basis of easy diagnosis and treatment of the soft tissue changes in the lower eyelid and malar region. PMID- 27398005 TI - Infraorbital Dark Circles: A Review of the Pathogenesis, Evaluation and Treatment. AB - Infraorbital dark circles represent a common and multifactorial challenge in the world of aesthetic medicine and are the result of a variety of factors including deep facial anatomy, soft tissue changes, as well as contributions from the skin. A variety of treatment options exist, and a customised management strategy can be developed for the particular anatomic changes present. A literature search using MEDLINE and non-MEDLINE sources was performed utilising keywords including: 'Dark circles' 'infraorbital dark circles', 'infraorbital pigment', 'under-eye circles' and 'lower eyelid bags'. A comprehensive review of the literature was performed and the data were assimilated with evidence from our practice. This review provides a detailed discussion of the aetiology, pathogenesis, evaluation and management of infraorbital dark circles. An understanding of the deep and superficial anatomy is crucial to the management of this complex entity. The armamentarium for treatment includes minimally invasive interventions such as makeup and cosmeceuticals, a variety of laser and chemical treatments, fillers and fat transfer, as well as more invasive surgical manoeuvres. PMID- 27398006 TI - Periorbital Injectables: Understanding and Avoiding Complications. AB - Periorbital rejuvenation with neurotoxins and dermal fillers address several aging changes. Safe and effective results require a thorough understanding of periorbital anatomy, proper injection techniques, and complications of these products. Prompt recognition and treatment of complications can minimize their adverse impacts. Complications can be divided into ischaemic and non-ischaemic effects. Hylauronidase, an enzyme that degrades hyaluronic acid, may improve outcomes after intravascular hyaluronic acid fillers. PMID- 27398007 TI - Blepharoplasty Basics for the Dermatologist. AB - Blepharoplasty is amongst the more frequently performed aesthetic procedures with surgery performed by physicians and surgeons across a variety of sub specialities. This paper, aimed at a dermatology audience, describes patient selection, eyelid anatomy, clinical examination and surgical steps to achieve successful upper and lower lid blepharoplasty outcomes. Recommendations for minimising complications are made and photographs used to illustrate important clinical and surgical features. PMID- 27398010 TI - Eyelash Transplantation for the Treatment of Vitiligo Associated Eyelash Leucotrichia. AB - BACKGROUND: Eyelash leucotrichia is cosmetically disfiguring condition and remains a therapeutic challenge in successful management of vitiligo. AIMS: To study the efficacy of eyelash transplantation in management of eyelash leucotrichia associated with vitiligo. MATERIALS AND METHODS: Fifteen patients with eyelash leucotrichia were treated with follicular unit transplantation. Improvement in leucotrichia was evaluated using objective assessment. RESULTS: Out of fifteen patients, good to excellent response was seen in 13 patients (86.67%), fair in one patient (6.66%) and poor in one patient (6.66%). CONCLUSION: Eyelash transplantation is safe and effective method for eyelash leucotrichia. PMID- 27398008 TI - Meeting the Challenges of Acne Treatment in Asian Patients: A Review of the Role of Dermocosmetics as Adjunctive Therapy. AB - Conventional acne treatment presents several challenges such as intolerable side effects and antibiotic resistance. Dermocosmetic products may be used to reduce these unwanted effects. Dermocosmetics include skin cleansers, topical sebum controllers, skin antimicrobial/anti-inflammatory agents, moisturizers, sunscreens, and camouflage products. Appropriate use of these products may help augment the benefit of acne treatment, minimize side effects, and reduce the need for topical antibiotics. In Asia, there is currently limited scientific data on the application and recommendations for dermocosmetic use in acne vulgaris (AV). This article reviews the evidence on dermocosmetics for AV and provides practice recommendations as discussed during the 4(th) Asia-Pacific Acne Leaders' Summit held in Bangkok, Thailand, on 7 and 8 February 2015. Through a premeeting survey, a series of plenary lectures, a stepwise program of discussion sessions, and Medline article review, the Expert Panel set forth relevant recommendations on the role of dermocosmetics as adjunct for treating AV in Asian patients. PMID- 27398009 TI - Objective Brow Height Measurements Following Pretrichial Brow Lift and Upper Lid Blepharoplasty. AB - BACKGROUND: As the ptotic brow drops below the supraorbital rim, it can exacerbate dermatochalasis by pushing the adjacent skin of the upper lid further down. AIM: The purpose of this study was to evaluate the outcomes associated with a combined pretrichial brow lift and upper lid blepharoplasty in patients with dermatochalasis and mild to moderate brow ptosis. MATERIALS AND METHODS: A retrospective case series of 46 patients with dermatochalasis and mild to moderate brow ptosis treated with a combined, bilateral pretrichial brow lift and upper lid blepharoplasty from January 2008 to December 2011. Main outcome measures included measurements of brow lift at 3 months post-operatively, complications encountered, patient satisfaction and surgeon satisfaction. RESULTS: Outcomes from 46 patients were evaluated. The mean brow lift was 1.85 mm at the lateral canthus, 1.54 mm at the lateral limbus, 1.31 mm at the mid-pupil, and 1.07 mm at the medial limbus. Brow lift at the lateral canthus was significantly more elevated than at the medial limbus (P < 0.001). Minor complications were encountered in seven of 46 patients (15.2%). Mean patient satisfaction score was 3.20 and surgeon satisfaction 3.24 (max = 4, very satisfied). CONCLUSIONS: The modified pretrichial brow lift offered effective lateral lift that complements an upper lid blepharoplasty. This technique was met with a high degree of patient and surgeon satisfaction, and had a minimal complication profile. PMID- 27398011 TI - Evaluation of Various Therapeutic Measures in Striae Rubra. AB - BACKGROUND: Striae are linear atrophic depressions that form in areas of dermal damage in the skin. As on date, no consensus or protocol exists for the treatment of stria rubra. Topical retinoids, chemical peels, microdermabrasion, radiofrequency, photothermolysis, intense pulsed light and lasers are some of the modalities used. AIMS AND OBJECTIVE: To compare the efficacy of various therapeutic modalities in striae rubra. METHODS: This prospective cohort study comprised of a total of fifty patients from August-2012 to October-2013 in a tertiary care center in Western India, Gujarat having striae rubra. They were randomly divided into five groups of ten patients each. Patients were evaluated on the basis of visual assessment, both by doctor as well as the patient. Group I was given topical tretinoin (0.1% w/w) gel applied once at night, Group II microdermabrasion (MDA) combined with trichloroacetic acid (TCA) (30%) peel, Group III-mesotherapy, Group IV-Q-switched Nd: YAG laser, and Group V-combination treatment of microdermabrasion, salicylic acid peel and retinol (yellow) peel. Patients were treated at an interval of 15 days for 2 months and then at monthly intervals. Objective assessment was done at 2(nd) month, 6(th) month, and at the end of 1(st) year. RESULTS: Patients in Group I treated with topical tretinoin showed the least response with 80% (8) of them showing minimal clinical improvement (0-25%) as compared to patients in Group V in which 60% (6) patients showed moderate clinical improvement (50-75%). While majority of the patients in Group II, III, and IV showed mild clinical improvement (25-50%). CONCLUSIONS: Striae rubra is a common cause of concern for adolescent population. Combination treatment with microdermabrasion, salicylic acid and retinol yellow peel gave superior results as compared to other therapeutic options. Mild to moderate improvement was seen with Nd: YAG laser, mesotherapy and MDA + TCA whereas minimal improvement were seen with topical tretinoin. PMID- 27398012 TI - Surgical Outcome in Patients Taking Concomitant or Recent Intake of Oral Isotretinoin: A Multicentric Study-ISO-AIMS Study. AB - BACKGROUND: The current standard recommendation is to avoid surgical interventions in patients taking oral isotretinoin. However, this recommendation has been questioned in several recent publications. AIM: To document the safety of cosmetic and surgical interventions, among patients receiving or recently received oral isotretinoin. MATERIALS AND METHODS: Association of Cutaneous Surgeons, India, in May 2012, initiated this study, at 11 centers in different parts of India. The data of 183 cases were collected monthly, from June 2012 to May 2013. Of these 61 patients had stopped oral isotretinoin before surgery and 122 were concomitantly taking oral isotretinoin during the study period. In these 183 patients, a total of 504 interventions were performed. These included[1] 246 sessions of chemical peels such as glycolic acid, salicylic acid, trichloroacetic acid, and combination peels;[2] 158 sessions of lasers such as ablative fractional laser resurfacing with erbium-doped yttrium aluminum garnet and CO2, conventional full face CO2 laser resurfacing, laser-assisted hair reduction with long-pulsed neodymium-doped yttrium aluminum garnet, diode laser, and LASIK surgery;[3] 27 sessions of cold steel surgeries such as microneedling, skin biopsy, subcision, punch elevation of scars, excision of skin lesion, and wisdom tooth extraction;[4] 1 session of electrosurgery. RESULTS: No significant side effects were noted in most patients. 2 cases of keloid were documented which amounted to 0.4% of side effects in 504 interventions, with a significant P value of 0.000. Reversible transient side effects were erythema in 10 interventions and hyperpigmentation in 15. CONCLUSION: The study showed that performing dermatosurgical and laser procedures in patients receiving or recently received isotretinoin is safe, and the current guidelines of avoiding dermatosurgical and laser interventions in such patients taking isotretinoin need to be revised. PMID- 27398013 TI - Clinical Photography for Periorbital and Facial Aesthetic Practice. AB - External cutaneous photography involves photographic documentation, which helps in treatment planning, documentation of facial features, teaching, publishing and pre- and post-procedural comparisons. The key is not simply documenting, but documenting it the right way and ensuring that photography is standardised and reproducible. In this review, basic photography techniques, standardised and reproducible angles such as frontal, oblique and lateral views and specific photographic angles for conditions such as facial rejuvenation are discussed. Use of photography accessories and a few tips on how to click good photographs in the examination room and how to achieve consistency in standardised photography are also presented. External photography in ophthalmic and facial plastic surgery like any other speciality too has standardised guidelines. Even small variations cause a drastic change in the photos and it's clinical and research value. Unless stringent criteria are met, the photographs lose their relevance and impact. PMID- 27398014 TI - Facial Basal Cell Carcinoma Treated with Topical 5% Imiquimod Cream with Dermoscopic Evaluation. AB - Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Surgical excision is considered to be the primary therapeutic modality wherever possible. For inoperable cases, 5% imiquimod seems to be a good alternative. We present two cases of nodular pigmented BCCs on the face in elderly women successfully treated with 5% imiquimod cream application resulting in complete clinical clearance of lesion as well as on histology and dermatoscopy. There was no recurrence of the lesion on 2 years follow-up for the first and 1.5 years for the second patient. PMID- 27398015 TI - An Unusual Eyelid Mass of Cysticercosis: A Twist in the Tale. AB - Cysticercosis is a parasitic infestation caused by the larval form of the tapeworm, Taenia solium (T. solium). The common sites for cysticerosis include the brain, eyes, and skeletal muscle. Ocular or adnexal involvement is commonly seen with the commonest ophthalmic site being subretinal space and the vitreous cavity. However, only a handful of cases of eyelid cysticercosis have been reported in the past. We report a rare and unusual case of isolated eyelid cysticercosis in a middle-aged woman masquerading as an asymptomatic slowly growing subcutaneous painless mass in the left eyelid which was presumed to be a benign skin mass, a cyst of appendageal origin such as an epidermoid cyst. This case highlights the ubiquitous nature of cysticercosis in tropical countries and the need for a high degree of suspicion while surgically treating subcutaneous masses. We would additionally emphasize the need to rule out neurocysticercosis in such cases. PMID- 27398016 TI - A Solitary Firm Nodule on the Palm. PMID- 27398017 TI - Use of Plastic Syringe as a Splint for Contracted Fingers. PMID- 27398018 TI - Observations on CO2 Laser Preparation of Recipient Site for Noncultured Cell Suspension Transplantation in Vitiligo. PMID- 27398019 TI - Regularized Structural Equation Modeling. AB - A new method is proposed that extends the use of regularization in both lasso and ridge regression to structural equation models. The method is termed regularized structural equation modeling (RegSEM). RegSEM penalizes specific parameters in structural equation models, with the goal of creating easier to understand and simpler models. Although regularization has gained wide adoption in regression, very little has transferred to models with latent variables. By adding penalties to specific parameters in a structural equation model, researchers have a high level of flexibility in reducing model complexity, overcoming poor fitting models, and the creation of models that are more likely to generalize to new samples. The proposed method was evaluated through a simulation study, two illustrative examples involving a measurement model, and one empirical example involving the structural part of the model to demonstrate RegSEM's utility. PMID- 27398020 TI - Investigating Evolutionary Dynamics of RHA1 Operons. AB - Grouping genes as operons is an important genomic feature of prokaryotic organisms. The comprehensive understanding of the operon organizations would be helpful to decipher transcriptional mechanisms, cellular pathways, and the evolutionary landscape of prokaryotic genomes. Although thousands of prokaryotes have been sequenced, genome-wide investigation of the evolutionary dynamics (division and recombination) of operons among these genomes remains unexplored. Here, we systematically analyzed the operon dynamics of Rhodococcus jostii RHA1 (RHA1), an oleaginous bacterium with high potential applications in biofuel, by comparing 340 prokaryotic genomes that were carefully selected from different genera. Interestingly, 99% of RHA1 operons were observed to exhibit evolutionary events of division and recombination among the 340 compared genomes. An operon that encodes all enzymes related to histidine biosynthesis in RHA1 (His-operon) was found to be segmented into smaller gene groups (sub-operons) in diverse genomes. These sub-operons were further reorganized with different functional genes as novel operons that are related to different biochemical processes. Comparatively, the operons involved in the functional categories of lipid transport and metabolism are relatively conserved among the 340 compared genomes. At the pathway level, RHA1 operons found to be significantly conserved were involved in ribosome synthesis, oxidative phosphorylation, and fatty acid synthesis. These analyses provide evolutionary insights of operon organization and the dynamic associations of various biochemical pathways in different prokaryotes. PMID- 27398021 TI - TMAinspiration: Decode Interdependencies in Multifactorial Tissue Microarray Data. AB - There are no satisfying tools in tissue microarray (TMA) data analysis up to now to analyze the cooperative behavior of all measured markers in a multifactorial TMA approach. The developed tool TMAinspiration is not only offering an analysis option to close this gap but also offering an ecosystem consisting of quality control concepts and supporting scripts to make this approach a platform for informed practice and further research. The TMAinspiration method is specifically focusing on the demands of the TMA analysis by controlling errors and noise by a generalized regression scheme while at the same time avoiding to introduce a priori too many constraints into the analysis of the data. So, we are testing partitions of a proximity table to find an optimal support for a ranking scheme of molecular dependencies. The idea of combining several partitions to one ensemble, which is balancing the optimization process, is based on the main assumption that all these perspectives on the cellular network need to be self consistent. Several application examples in breast cancer and one in squamous cell carcinoma demonstrate that this procedure is nicely confirming a priori knowledge on the expression characteristics of protein markers, while also integrating many new results discovered in the treasury of a bigger TMA experiment. The code and software are now freely available at: http://complex systems.uni-muenster.de/tma_inspiration.html. PMID- 27398022 TI - Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents. AB - OBJECTIVE: The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. METHODS: We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. RESULTS: Baseline serum creatinine was 57.8 +/- 34.5 umol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase associated lipocalin levels and for serum cystatin C levels. CONCLUSIONS: Urinary IL-18 and NAG levels increased transiently after administration of gadolinium based contrast agents in patients with normal renal function. PMID- 27398023 TI - Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. AB - Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients. PMID- 27398025 TI - Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer. AB - PURPOSE AND METHODS: Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged >=18 years with advanced/metastatic breast cancer and <=3 prior chemotherapies (<=2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m(2) on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m(2) on days 1-14 (21-day cycles). RESULTS: In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS: Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION PRIMARY STUDY: This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID- 27398024 TI - The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation. AB - The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (-)-Delta(9) tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure-CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure-activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID- 27398026 TI - Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population. AB - Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (-460T>C), rs699947 (-2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an Iranian population in southeast of Iran. This case control study was done on 250 BC patients and 215 healthy women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or PCR was used to genotype the polymorphisms. Our findings showed that VEGF rs699947 variant increased the risk of BC (OR = 1.71, 95% CI = 1.15-2.54, P = 0.009, CA vs CC; OR = 2.12, 95% CI = 1.14-3.93, P = 0.021, AA vs CC; OR = 1.78, 95% CI = 1.22-2.60, P = 0.004, CA+AA vs CC; OR = 1.47, 95% CI = 1.12-1.92, P = 0.005, A vs C). The VEGF rs3025039, rs2010963, rs833061, and rs35569394 variants were not associated with risk/protection of BC. In conclusion, our results proposed that VEGF rs699947 polymorphism may increase the risk of BC development. Furthers studies with larger sample sizes and different ethnicities are necessary to confirm our findings. PMID- 27398027 TI - DNA Damage among Wood Workers Assessed with the Comet Assay. AB - Exposure to wood dust, a human carcinogen, is common in wood-related industries, and millions of workers are occupationally exposed to wood dust worldwide. The comet assay is a rapid, simple, and sensitive method for determining DNA damage. The objective of this study was to investigate the DNA damage associated with occupational exposure to wood dust using the comet assay (peripheral blood samples) among nonsmoking wood workers (n = 31, furniture and construction workers) and controls (n = 19). DNA damage was greater in the group exposed to composite wood products compared to the group exposed to natural woods and controls (P < 0.001). No difference in DNA damage was observed between workers exposed to natural woods and controls (P = 0.13). Duration of exposure and current dust concentrations had no effect on DNA damage. In future studies, workers' exposures should include cumulative dust concentrations and exposures originating from the binders used in composite wood products. PMID- 27398028 TI - A Systematic Review of Effects of Waterpipe Smoking on Cardiovascular and Respiratory Health Outcomes. AB - BACKGROUND: Waterpipe smoking (WPS) is a social custom common in many Middle Eastern, North African, and Asian countries and has become increasingly popular in the US, especially among youth; however, WPS smoking may be increasing in the US adult population as well. There is a common belief among waterpipe (WP) smokers that WPS is less harmful than smoking cigarettes. Thus, this review aims to systematically explore the literature on the effects of WP tobacco smoking with a particular focus on cardiovascular and respiratory health outcomes as well as on oxidative stress, immunity, and cell cycle interference health outcomes. METHODOLOGY: We conducted a systematic review, guided by the criteria of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses, using the following online databases MEDLINE, CINAHL, ScienceDirect, PMC, and Cochrane Library. Results were summarized qualitatively. RESULTS: Forty studies met the inclusion criteria established for this review. Based on the existing evidence, several cardiovascular and respiratory physiologic health indicators and conditions have been shown to be negatively affected by WPS. In addition to the effects of nicotine and chemical toxicant exposures, WPS was significantly associated with an increase in heart rate, blood pressure, and lower pulmonary function test results, as well as a number of health conditions such as lung cancer, alterations in oxidative stress, immunity, and cell cycle interference. CONCLUSION: The current literature provides evidence that WPS is associated with a number of negative health indicators and outcomes. There is need for more research related to WPS and its effects on health so that appropriate campaigns and prevention interventions can be implemented to control the epidemic increase of WPS in the US. PMID- 27398031 TI - Differential Induction of Flavonoids in Groundnut in Response to Helicoverpa armigera and Aphis craccivora Infestation. AB - Flavonoids are important plant secondary metabolites, which protect plants from various stresses, including herbivory. Plants differentially respond to insects with different modes of action. High performance liquid chromatography (HPLC) fingerprinting of phenols of groundnut (Arachis hypogaea) plants with differential levels of resistance was carried out in response to Helicoverpa armigera (chewing insect) and Aphis craccivora (sucking pest) infestation. The genotypes used were ICGV 86699, ICGV 86031, ICG 2271 (NCAc 343), ICG 1697 (NCAc 17090), and JL 24. Most of the identified compounds were present in H. armigera- and A. craccivora-infested plants of ICGV 86699. Syringic acid was observed in all the genotypes across the treatments, except in the uninfested control plants of ICG 2271 and aphid-infested plants of ICG 1697. Caffeic acid and umbelliferone were observed only in the H. armigera-infested plants of ICGV 86699. Similarly, dihydroxybenzoic acid and vanillic acid were observed in H. armigera- and aphid infested plants of ICG 2271 and JL 24, respectively. The peak areas were transformed into the amounts of compounds by using internal standard peak areas and were expressed in nanograms. Quantities of the identified compounds varied across genotypes and treatments. The common compounds observed were chlorogenic, syringic, quercetin, and ferulic acids. These results suggest that depending on the mode of feeding, flavonoids are induced differentially in groundnut plants. PMID- 27398032 TI - Effects of Nasal Calcitonin vs. Oral Gabapentin on Pain and Symptoms of Lumbar Spinal Stenosis: A Clinical Trial Study. AB - Lumbar spinal stenosis (LSS) is a chronic and prevalent disease that occurs in 10.8% of the general population, mostly in old age. We designed the first clinical trial study to compare the effects of administering the nasal salmon calcitonin spray and gabapentin in patients with LSS. In this clinical trial, 90 patients with symptoms of neurogenic claudication and magnetic resonance imaging proven LSS were randomly assigned to nasal salmon calcitonin, gabapentin, or placebo treatments for eight weeks (30 participants in each group). This was followed by a washout period of four weeks. After three months of study and after four weeks off the prescription, mean values of Oswestry Disability Index in the calcitonin, gabapentin, and control groups were 23 +/- 12.05, 32 +/- 16.08, and 38 +/- 22.09, respectively (P <= 0.05, calcitonin group vs. gabapentin group, and P <= 0. 001, calcitonin group vs. control group with respect to pretreatment scores). Thus, three months after the treatment, although most of the patients in the control group had a satisfactory period of improvement, the improvement in the calcitonin group was more than the other two groups with a significant difference (P <= 0.05 when compared to gabapentin group and P <= 0.01 when compared to placebo group). We revealed that the 200 International Unit (IU) and nasal calcitonin spray daily are more effective compared to 300 mg gabapentin three times per day and the placebo effect for eight weeks of treatment of symptoms of patients with LSS. PMID- 27398030 TI - Quantitative Perfusion and Permeability Biomarkers in Brain Cancer from Tomographic CT and MR Images. AB - Dynamic contrast-enhanced perfusion and permeability imaging, using computed tomography and magnetic resonance systems, are important techniques for assessing the vascular supply and hemodynamics of healthy brain parenchyma and tumors. These techniques can measure blood flow, blood volume, and blood-brain barrier permeability surface area product and, thus, may provide information complementary to clinical and pathological assessments. These have been used as biomarkers to enhance the treatment planning process, to optimize treatment decision-making, and to enable monitoring of the treatment noninvasively. In this review, the principles of magnetic resonance and computed tomography dynamic contrast-enhanced perfusion and permeability imaging are described (with an emphasis on their commonalities), and the potential values of these techniques for differentiating high-grade gliomas from other brain lesions, distinguishing true progression from posttreatment effects, and predicting survival after radiotherapy, chemotherapy, and antiangiogenic treatments are presented. PMID- 27398034 TI - Renal Artery Stenosis in a Young Female without Fibromuscular Dysplasia with Literature Review. AB - Renal artery stenosis (RAS) is rare in young patients without fibromuscular dysplasia (FMD). RAS is primarily classified as having two major etiologies, namely, atherosclerosis and FMD, with 90% and 10%, respectively. We report a case of a female in her mid 20s who developed hypertension due to RAS with no evidence of FMD or underlying renal dysfunction and underwent successful angioplasty and stenting. PMID- 27398033 TI - Volume Measurements in Aortic Root Assessment Using Two-Dimensional Echocardiography. AB - BACKGROUND: Aortic dilatation is associated with the presence of aortic diseases. Current guidelines for assessing the aortic root (AoR) depend on linear measurements acquired by two-dimensional (2D) echocardiography. We considered that real-time three-dimensional echocardiography, which correlates better with AoR volume obtained by computed tomography, is widely unavailable, and therefore, there is a need to determine the AoR volume using 2D echocardiography. METHODS: Fifty-one consecutive apparently healthy volunteers were recruited and subsequently divided into three age groups. Specified planes of acquisition and previously defined landmarks were identified, and phases of the cardiac cycle that allowed for measurement standardization were used. Volume was determined by the modified Simpson's method. RESULTS: Although the average diastolic and systolic volume measurements of the AoR dimensions were not significantly different across the three age groups in the study population, a highly significant difference was observed in the volume measurements between male and female normotensive persons, P < 0.01 in each case. AoR volume measurements were five times in the diseased compared with the normotensive individuals; however, linear measurements were only 1.5 times in size of the normal individuals. Both point and interval estimates of the volume measurements of AoR in adult normotensives in three age groups were presented as baseline information. CONCLUSIONS: We hereby present a novel way to determine the AoR volume using 2D echocardiography and the normal reference range with respect to age and gender. We also established the relevance of our measurement by comparing the normal population with two isolated diseased aortas. PMID- 27398035 TI - Outcomes of DES in Diabetic and Nondiabetic Patients with Complex Coronary Artery Disease after Risk Stratification by the SYNTAX Score. AB - Diabetes mellitus (DM) increases the risk of adverse outcomes after coronary revascularization. Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). AIM: The aim of this study was to assess the outcomes of drug-eluting stent (DES) insertion in DM and non-DM patients with complex coronary artery disease (CAD) after risk stratification by the percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score. METHODS AND RESULTS: We performed multivessel percutaneous coronary intervention (PCI) for 601 lesions in 243 DM patients and 1,029 lesions in 401 non-DM patients. All included patients had MVD and one or more lesions of type B2/C. The two-year outcomes and event rates were estimated in the DM and non-DM patients using Kaplan-Meier analyses. The baseline SYNTAX score was <=22 in 84.8% vs. 84%, P = 0.804, and 23-32 in 15.2% vs. 16%, P = 0.804, of the DM and non-DM patients, respectively. The number of diseased segments treated (2.57 +/- 0.75 vs. 2.47 +/- 0.72; P = 0.066) and stents implanted per patient (2.41 +/- 0.63 vs. 2.32 +/- 0.54; P = 0.134) were similar in both groups. After a mean follow-up of 642 +/- 175 days, there were no differences in the major adverse cardiac and cerebrovascular events (MACCE; 26.7% vs. 20.9%; P = 0.091), composite end point of all-cause death/myocardial infarction (MI)/stroke (12.3% vs. 9%; P = 0.172), individual MACCE components of death (3.7% vs. 3.2%; P = 0.754), MI (6.6% vs. 4%; P = 0.142), and absence of stroke in the DM and non-DM patients. An increased need for repeat revascularization was observed in DM patients (18.5% vs. 10.2%; P = 0.003). In the multivariate analysis, DM was an independent predictor of repeat revascularization (hazard ratio: 1.818; 95% confidence interval: 1.162-2.843; P = 0.009). CONCLUSIONS: DES implantation provides favorable early and mid-term results in both DM and non-DM patients undergoing PCI for complex lesions. After a mean follow-up of two years, DM and non-DM patients with complex CAD treated by PCI using new-generation DES showed no differences with regard to MACCE and other secondary end points. However, higher rates of ischemia-driven repeat revascularization were observed in DM patients. PMID- 27398029 TI - Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID- 27398037 TI - Heart Failure: An Exploration of Recent Advances in Research and Treatment. PMID- 27398036 TI - Hypertension among Outpatients at a General Hospital in South Angola: Prevalence, Awareness, Treatment, and Control. AB - OBJECTIVE: This study aimed to assess the prevalence, awareness, treatment, and control of hypertension in patients attending an outpatient clinic at a general hospital in Huambo, South Angola. METHODS: A total of 265 subjects aged 18 years and older were included. Evaluation included complete interview and blood pressure measurement using a validated automatic device. RESULTS: The prevalence rates of hypertension and prehypertension were 38.5% (95% confidence interval [CI]: 32.83%-44.90%) and 30.20% (95% CI: 24.52%-36.22%), respectively. Hypertension was associated with age (>35 years; odds ratio [OR] = 10.09, 95% CI: 5.46-18.66, P < 0.01) and female gender (OR = 1.81, 95% CI: 1.08-3.05, P = 0.02). Among total hypertensive patients, 54.9% were aware of their diagnosis, 28.43% were in treatment, and 7.84% had controlled blood pressure. Lack of awareness was significantly higher in younger (age <= 37 years; OR = 3.28, 95% CI: 1.13-9.49, P = 0.02). CONCLUSION: This study revealed a high prevalence of hypertension, with low awareness, treatment, and control rates. Greater efforts are necessary to overcome these challenges. PMID- 27398038 TI - Aggressive Lymphoma "Sarcoma Mimicker" Originating in the Gluteus and Adductor Muscles: A Case Report and Literature Review. AB - Extranodal lymphoma (ENL) occurs in approximately 30%-40% of all patients with non-Hodgkin lymphoma and has been described in almost all organs and tissues. However, diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin lymphoma, primarily arising in the retroperitoneal region. In this article, we report a rare case of an adult male diagnosed with primary diffuse large B-cell lymphoma of the gluteal and adductor muscles with aggressive bone involvement. All appropriate radiological and histopathological studies were done for diagnosis and staging. After discussion with the lymphoma multidisciplinary team, it was agreed to start on R-CHOP protocol (rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin(r)), and prednisone) as the standard of care, which was later changed to R-CODOX-M/R-IVAC protocol (rituximab, cyclophosphamide, vincristine (Oncovin(r)), doxorubicin, and high dose methotrexate alternating with rituximab, ifosfamide, etoposide, and high dose cytarabine) due to inadequate response. Due to the refractory aggressive nature of the disease, subsequent decision of the multidisciplinary team was salvage chemotherapy and autologous stem cell transplant. The aim of this case report was to describe and evaluate the clinical presentation and important radiological features of extranodal lymphoma affecting the musculoskeletal system. PMID- 27398039 TI - Ultrasound for the Pulmonary Consultant. AB - Bedside ultrasonographic assessment of the lung and pleura provides rapid, noninvasive, and essential information in diagnosis and management of various pulmonary conditions. Ultrasonography helps in diagnosing common conditions, including consolidation, interstitial syndrome, pleural effusions and masses, pneumothorax, and diaphragmatic dysfunction. It provides procedural guidance for various pulmonary procedures, including thoracentesis, chest tube insertion, transthoracic aspiration, and biopsies. This article describes major applications of ultrasonography for the pulmonary consultant along with illustrative figures and videos. PMID- 27398040 TI - Changes in Characteristics and Treatment Patterns of Patients with Newly Diagnosed Type 2 Diabetes in a Large United States Integrated Health System between 2008 and 2013. AB - To assess changes in the clinical characteristics and treatment patterns of patients with newly diagnosed type 2 diabetes (T2D), the electronic health record system at Cleveland Clinic was used to create cross-sectional summaries of all patients with new-onset T2D in 2008 and 2013. Differences between the 2008 and 2013 data sets were assessed after adjusting for age, gender, race, and income. Approximately one-third of patients with newly diagnosed T2D in 2008 and 2013 had an A1C >=8%, suggesting the continued presence of a delayed recognition of the disease. Patients with newly diagnosed T2D in 2008 were older than those in 2013. Hypertension, cardiovascular disease, and neuropathy were highly prevalent among patients diagnosed with T2D. The prevalence of neuropathy, cerebrovascular disease, and peripheral vascular disease increased from 2008 to 2013. Metformin was the most commonly prescribed antidiabetic medication. Sulfonylurea usage remained unchanged, while use of thiazolidinediones decreased considerably. PMID- 27398042 TI - Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice. AB - BACKGROUND: Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice. MATERIAL AND METHODS: We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comte cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice. RESULTS: From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0-1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13-11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 +/- 8191?, and median cost was 7917? (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months). CONCLUSIONS: The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment. PMID- 27398043 TI - Should Sentinel Lymph Node Biopsy for Patients with Early Breast Cancer Be Abandoned? Not So Fast. AB - As major advances are made in the management of early breast cancer, the role of sentinel lymph node biopsy (SLNBx) has been called into question. However, before abandoning SLNBx, a critical appraisal of its role should be done because we believe that it remains a critical component of care, especially when tailoring patient's adjuvant therapy. This commentary provides cogent arguments in favor of SLNBx in the management of patients with early breast cancer. PMID- 27398041 TI - Fertility Risk Assessment and Preservation in Male and Female Prepubertal and Adolescent Cancer Patients. AB - Cancer represents the second cause of death in prepubertal children and adolescents, although it is currently associated with an overall survival rate of 80%-85%. The annual incidence rate is 186.6 per 1 million children and adolescents aged up to 19 years. Both disease and treatment options are associated with life-altering, long-term effects that require monitoring. Infertility is a common issue, and as such, fertility preservation represents an essential part in the management of young patients with cancer who are at risk of premature gonadal failure. This review deals with the up-to-date available data on fertility risk assessment and preservation strategies that should be addressed prior to antineoplastic therapy in this vulnerable subgroup of cancer patients. PMID- 27398044 TI - The Diabetic Health of African American Grandmothers Raising their Grandchildren. AB - PURPOSE: The purpose of this study is to compare the health of primary caregiving African American grandmothers with diabetes with African American women with diabetes who were not primary caregivers. DESIGN: Using a comparative, descriptive, cross-sectional design, 34 African American primary caregiving grandmothers were compared with 34 non-caregiving women with diabetes mellitus; women aged 55-75 years were recruited for this study throughout the central Arkansas. METHODS: To measure the overall health, data on blood pressure, body mass index measurements, HbA1c levels, total cholesterol, and urine protein and creatinine levels were collected from all the participants. RESULTS: Statistically significant differences between the caregivers and non-caregivers groups in systolic pressure (t = -3.42, P = 0.001) and diastolic pressure (t = 3.790, P = 0.000) and urine protein (W = 294.00, P = 0.000) were noted. Additionally, a clinically significant difference in HbA1c was noted between groups. CONCLUSION: Differences in systolic and diastolic pressures, urine protein, and clinically significant differences in HbA1c suggest that African American primary caregiving grandmothers with diabetes mellitus may have more difficulty in maintaining their diabetic health than non-caregiving African American women. PMID- 27398047 TI - The training paths and practice patterns of Canadian paediatric residency graduates, 2004-2010. AB - BACKGROUND: The Paediatric Chairs of Canada have been proactive in workforce planning, anticipating paediatric job opportunities in academic centres. To complement this, it is important to characterize the practice profiles of paediatricians exiting training, including those working outside of tertiary care centres. OBJECTIVE: To describe the training paths and the practice patterns of Canadian paediatric residency graduates. METHODS: A survey was completed in 2010 to 2011 by Canadian program directors regarding residents completing core paediatrics training between 2004 and 2010. Data collection included training path after completing core paediatrics training and practice type after graduation. RESULTS: Of 699 residents completing their core training in paediatrics, training path data were available for 685 (98%). Overall, 430 (63%) residents completed subspecialty training while 255 (37%) completed general paediatrics training only. There was a significant increase in subspecialty training, from 59% in earlier graduates (2004 to 2007) to 67% in later graduates (2008 to 2010) (P=0.037). Practice pattern data after completion of training were available for 245 general paediatricians and 205 subspecialists. Sixty-nine percent of general paediatricians were community based while 85% of subspecialists were hospital based in tertiary or quaternary centres. Of all residents currently in practice, only 36 (8%) were working in rural, remote or underserviced areas. CONCLUSIONS: Almost two-thirds of recent Canadian paediatric graduates pursued subspecialty training. There was a significant increase in the frequency of subspecialty training among later-year graduates. Few graduates are practicing in rural or underserviced areas. Further studies are needed to determine whether these trends continue and their impact on the future paediatric workforce in Canada. PMID- 27398046 TI - Creating a student-led health magazine with an urban, multicultural, resource restricted elementary school: Approach, process and impact. AB - BACKGROUND: Health magazines effectively deliver health information. No data regarding student-led magazines to promote health exist. OBJECTIVE: To evaluate whether children's health knowledge, interests and lifestyle choices improve following distribution of a student-led health magazine. METHODS: Elementary students worked with teachers and paediatric residents to publish a health magazine. A healthy lifestyle challenge page promoted reduction in soda pop consumption. Pre- and poststudent questionnaires explored knowledge, interests and behaviours related to health. RESULTS: Sex and grade distributions were similar in pre- and post-questionnaires. Ninety-seven percent of children reported the magazine helped them learn about health. Pre- and postknowledge scores did not differ (P=0.36). Following distribution, the percentage of students who reported drinking no soda increased from 43% to 67% (P=0.004), and those who reported drinking <2 glasses of soda per day increased from 66% to 85% (P=0.01). CONCLUSIONS: A student-led health magazine was effective in motivating short-term student-reported behavioural change. PMID- 27398048 TI - Discontinuation of paediatric injectable digoxin: A loss for optimal drug therapy in children. AB - In early 2015, the paediatric formulation of injectable digoxin (50 MUg/mL) was discontinued in Canada. The only remaining injectable formulation is five times more concentrated. This recent event has major implications for paediatric hospitals all over the country. The use of a more concentrated formulation is of particular concern in low-weight infants because the required volumes of digoxin are almost impossible to draw precisely. Such a situation is problematic because of the narrow therapeutic index of digoxin. There are different ways to deal with this inconvenient situation; however, none is as efficient or safe for infants as the discontinued formulation. The authors believe it remains imperative that patients requiring intravenous digoxin be treated with the safest and most efficient formulation possible, regardless of their age or size. PMID- 27398045 TI - Psychosocial Variables Related to Why Women are Less Active than Men and Related Health Implications. AB - This article reviews psychosocial influences on women's participation in physical activity as they differ from men and how associated activity differences impact women's risk for a number of chronic diseases. This topic directly aligns with the mission of this special edition related to disparities in women's health as the typically lower level of physical activity in females directly impacts their health. On average, females participate in physical activity at lower rates than their male counterparts. These lower rates of physical activity are directly related to both incidence of and outcomes from cardiovascular disease, type 2 diabetes, and breast and gynecological cancers. The relationship between psychosocial factors that are understood to affect physical activity differs between men and women. Specifically, self-efficacy, social support, and motivation are empirically substantiated factors that found to impact physical activity participation among women differently than men. Understanding these relationships is integral to designing effective interventions to target physical activity participation in women so that the related health risks are adequately addressed. PMID- 27398049 TI - The Canadian Biliary Atresia Registry: Improving the care of Canadian infants with biliary atresia. AB - Biliary atresia is the most common cause of end-stage liver disease and liver cirrhosis in children, and the leading indication for liver transplantation in the paediatric population. There is no cure for biliary atresia; however, timely diagnosis and early infant age at surgical intervention using the Kasai portoenterostomy optimize the prognosis. Late referral is a significant problem in Canada and elsewhere. There is also a lack of standardized care practices among treating centres in this country. Biliary atresia registries currently exist across Europe, Asia and the United States. They have provided important evidence-based information to initiate changes to biliary atresia care in their countries with improvements in outcome. The Canadian Biliary Atresia Registry was initiated in 2013 for the purpose of identifying best standards of care, enhancing public education, facilitating knowledge translation and advocating for novel national public health policy programs to improve the outcomes of Canadian infants with biliary atresia. PMID- 27398050 TI - Case 1: A 12-year-old boy with acute liver failure. PMID- 27398051 TI - Case 2: A persistent hyperpigmented plaque on the neck. PMID- 27398052 TI - Case 3: A 28-month-old with esotropia and acute lymphoblastic leukemia. PMID- 27398053 TI - Case 4: 'Spontaneous' emphysema in a toddler. PMID- 27398054 TI - Decongestants, antihistamines and nasal irrigation for acute sinusitis in children. PMID- 27398056 TI - Assessment of cardiorespiratory stability using the infant car seat challenge before discharge in preterm infants (<37 weeks' gestational age). AB - Preterm infants younger than 37 weeks corrected gestational age are at increased risk for abnormal control of respiration. The infant car seat challenge has been used as a screening tool to ensure cardiorespiratory stability before discharging preterm infants from many hospitals in Canada. While it is clear that infants placed in a car seat are more likely to experience oxygen desaturation and/or bradycardia than when they are supine, neither positioning predicts an adverse neurodevelopmental outcome or mortality post-discharge. A review of the literature yielded insufficient evidence to recommend routine use of the infant car seat challenge as part of discharge planning for preterm infants. This finding has prompted a change in recommendation from a previous Canadian Paediatric Society position statement published in 2000. PMID- 27398055 TI - Folate and neural tube defects: The role of supplements and food fortification. AB - Periconceptional folic acid significantly reduces the risk of neural tube defects. It is difficult to achieve optimal levels of folate by diet alone, even with fortification of flour, especially because flour consumption in Canada is slightly decreasing. Intermittent concerns have been raised concerning possible deleterious effects of folate supplementation, including the masking of symptoms of vitamin B12 deficiency and an association with cancer, especially colorectal cancer. Both concerns have been disproved. The Canadian Paediatric Society endorses the following steps to enhance folate intake in women of child-bearing age: encouraging the consumption of folate-rich foods such as leafy vegetables, increasing the level of folate food fortification, taking a supplement containing folate and B12, and providing free folate supplementation to disadvantaged women of child-bearing age. These recommendations are consistent with those of the Society of Obstetricians and Gynaecologists of Canada. PMID- 27398057 TI - Sexual assault of adolescent girls: Examining acute care service use. PMID- 27398058 TI - Barriers to and facilitators of implementing shared decision making and decision support in a paediatric hospital: A descriptive study. AB - OBJECTIVE: To explore multiple stakeholders' perceived barriers to and facilitators of implementing shared decision making and decision support in a tertiary paediatric hospital. METHODS: An interpretive descriptive qualitative study was conducted using focus groups and interviews to examine senior hospital administrators', clinicians', parents' and youths' perceived barriers to and facilitators of shared decision making and decision support implementation. Data were analyzed using inductive thematic analysis. RESULTS: Fifty-seven stakeholders participated. Six barrier and facilitator themes emerged. The main barrier was gaps in stakeholders' knowledge of shared decision making and decision support. Facilitators included compatibility between shared decision making and the hospital's culture and ideal practices, perceptions of positive patient and family outcomes associated with shared decision making, and positive attitudes regarding shared decision making and decision support. However, youth attitudes regarding the necessity and usefulness of a decision support program were a barrier. Two themes were both a barrier and a facilitator. First, stakeholder groups were uncertain which clinical situations are suitable for shared decision making (eg, new diagnoses, chronic illnesses, complex decisions or urgent decisions). Second, the clinical process may be hindered if shared decision making and decision support decrease efficiency and workflow; however, shared decision making may reduce repeat visits and save time over the long term. CONCLUSIONS: Specific knowledge translation strategies that improve shared decision making knowledge and match specific barriers identified by each stakeholder group may be required to promote successful shared decision making and decision support implementation in the authors' paediatric hospital. PMID- 27398059 TI - Concussion and its management: What do parents know? AB - OBJECTIVES: To determine the sensitivity of parental suspicion of concussion relative to paediatric emergency physicians in children who presented to an emergency department (ED) with a head injury. A secondary objective was to examine the variables associated with parental suspicion of concussion concordant with that of a physician. METHODS: Parents of children five to 18 years of age presenting to an urban paediatric ED with a nonstructural head injury completed a 24-item questionnaire. RESULTS: Of the 577 eligible parents, 495 (85.8%) consented to participate. The sensitivity of parental suspicion for concussion was 40.0% (95% CI 33.2% to 47.2%), while the specificity was 58.3% (95% CI 52.4% to 64.0%). The variable of child age >=10 years was associated with an increased odds (OR 3.0) of a parental suspicion of concussion concordant with that of a physician; parent age, parent sex, mechanism of head injury and history of concussion in the child were not. Although 453 (91.5%) parents would stop activity if they believed their child sustained a concussion, only 159 (32.1%) were familiar with return-to-play guidelines. CONCLUSIONS: Parents often did not suspect a concussion when it was ultimately diagnosed by a paediatric emergency physician, although they were more likely to do so in older children. Only approximately one-third were aware of return-to-play guidelines. To enhance the potential for parent-driven advocacy in the recognition and management of concussion, these data support the need for increased parental education on this injury. PMID- 27398060 TI - Human antibody response to dengue virus: implications for dengue vaccine design. AB - Dengue, a global health threat, is a leading cause of morbidity and mortality in most tropical and subtropical countries. Dengue can range from asymptomatic, relatively mild dengue fever to severe and life-threatening dengue hemorrhagic fever. Disease severity and outcome is largely associated with the host immune response. Several candidate vaccines in clinical trials appear promising as effective measures for dengue disease control. Vaccine development has been hampered by safety and efficacy issues, driven by a lack of understanding of the host immune response. This review focuses on recent research findings on the dengue host immune response, particularly in humans, and the relevance of these findings to challenges in vaccine development. PMID- 27398061 TI - Diffuse and disseminated cutaneous leishmaniasis: clinical cases experienced in Ecuador and a brief review. AB - BACKGROUND: In Ecuador, cutaneous leishmaniasis (CL) is prevalent countrywide, but only one case of diffuse-CL and two cases of disseminated-CL were experienced during our research activities more than 30 years from 1982 to date. These three patients suffered from multiple lesions distributed at a wide range of the body surface, revealing difficulty to clinically differentiate each other. METHODS: There is a considerable confusion of the use and/or differentiation of the terminologies (terms) between the two disease forms, diffuse-CL and disseminated CL. One of the aims of the present study is to clarify the difference between the two disease forms, mainly based on the cases experienced in Ecuador. RESULTS: The disseminated-CL case newly reported here was clinically very similar to the diffuse-CL case, but the former showed the following marked differences from the latter: (1) the organisms isolated were identified as the parasites of Leishmania (Viannia) guyanensis/panamensis, which are also known as the causative agents of disseminated-CL in different endemic countries of the New World; (2) the patient was sensitive against antimonials; and (3) mucosal involvement was observed, which is never observed in diffuse-CL. CONCLUSIONS: In the text, three clinical cases, one diffuse-CL and two disseminated-CL, were presented. Furthermore, a bibliographic comparison of the features between the two disease forms was made, and a brief comment was also given. PMID- 27398062 TI - Molecular and phenotypic characterization of methicillin-resistant Staphylococcus aureus isolates from a tertiary hospital in the Philippines. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) poses a major threat to public health worldwide. There are relatively few studies addressing the molecular epidemiology of MRSA in the Philippines. METHODS: This study characterized MRSA isolates in terms of their antimicrobial susceptibility profile, the SCCmec type, and the presence of lukF-lukS genes for Panton Valentine leukocidin (PVL) and determined the relatedness of the isolates by random amplified polymorphic DNA (RAPD)-polymerase chain reaction (PCR). RESULTS: A total of 236 S. aureus were isolated from clinical specimens of the Makati Medical Center in Makati City, Philippines, between January 2013 and June 2013, and 108 or 45.76 % were found to be MRSA. Results showed that the MRSA strains were resistant to trimethoprim-sulfamethoxazole (20.37 %), azithromycin (10.19 %), gentamicin (5.56 %), and linezolid (4.63 %), while all were susceptible to vancomycin, nitrofurantoin, levofloxacin, minocycline, rifampin, and tetracycline. One isolate was found positive for inducible clindamycin resistance. All of the 108 MRSA strains were confirmed to carry the mecA and SCCmec genes, while the PVL genes were detected in 41 (38 %) of the isolates. Ninety-six isolates (89 %) carried SCCmec type IV, while the remaining isolates carried SCCmec type I (11 isolates) or type III (one isolate). CONCLUSION: This study is the first to present a comprehensive MRSA surveillance data with molecular characterization in a tertiary hospital in the Philippines. PMID- 27398063 TI - New era for Tropical Medicine and Health. PMID- 27398064 TI - Third-stage Gnathostoma spinigerum larva excretory secretory antigens modulate function of Fc gamma receptor I-mediated monocytes in peripheral blood mononuclear cell culture. AB - BACKGROUND: Third (infective)-stage Gnathostoma spinigerum larvae (L3) mainly cause human gnathostomiasis. G. spinigerum L3 migrate throughout the subcutaneous tissues, vital organs, and central nervous system and can cause various pathogenesis including sudden death. Interestingly, G. spinigerum L3 can survive and evade host cellular immunity for months or years. The effects of G. spinigerum excretory-secretory (ES) products involved in larval migration and immune-evasive strategies are unknown. Monocytes are innate immune cells that act as phagocytic and antigen-presenting cells and also play roles against helminthic infections via a complex interplay between other immune cells. Fc gamma receptor I (FcgammaRI) is a high-affinity receptor that is particularly expressed on monocytes, macrophages, and dendritic cells. The cross-linking of FcgammaRI and antigen-antibody complex initiates signal transduction cascades in phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). This study investigated whether ES antigen (ESA) from G. spinigerum L3 affects monocyte functions. RESULTS: Cultures of normal peripheral blood mononuclear cells (PBMC) separated from healthy buffy coats were used as a human immune cell model. ESA was prepared from G. spinigerum L3 culture. Using Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the effect of ESA to down-regulate FcgammaRI mRNA expression in monocytes during 90 min of observation was not well delineated. Flow cytometry analysis revealed a significant phenotypic-decreased FcgammaRI expression on the monocyte surface at 12 hours (h) of cultivation with the ESA (p = 0.033). Significantly reduced monocyte-mediated phagocytosis capacity was consistently observed after 12 h of ESA pretreatment (p = 0.001). CONCLUSIONS: Our results suggest that G. spinigerum ESA modulates monocyte function via depletion of FcgammaRI expression. This study provides preliminary information for future in-depth studies to elucidate mechanisms of the immune-evasive strategy of G. spinigerum larvae. PMID- 27398065 TI - The Effects of Age and Set Size on the Fast Extraction of Egocentric Distance. AB - Angular direction is a source of information about the distance to floor-level objects that can be extracted from brief glimpses (near one's threshold for detection). Age and set size are two factors known to impact the viewing time needed to directionally localize an object, and these were posited to similarly govern the extraction of distance. The question here was whether viewing durations sufficient to support object detection (controlled for age and set size) would also be sufficient to support well-constrained judgments of distance. Regardless of viewing duration, distance judgments were more accurate (less biased towards underestimation) when multiple potential targets were presented, suggesting that the relative angular declinations between the objects are an additional source of useful information. Distance judgments were more precise with additional viewing time, but the benefit did not depend on set size and accuracy did not improve with longer viewing durations. The overall pattern suggests that distance can be efficiently derived from direction for floor-level objects. Controlling for age-related differences in the viewing time needed to support detection was sufficient to support distal localization but only when brief and longer glimpse trials were interspersed. Information extracted from longer glimpse trials presumably supported performance on subsequent trials when viewing time was more limited. This outcome suggests a particularly important role for prior visual experience in distance judgments for older observers. PMID- 27398066 TI - Synthesis of compositionally controllable Cu2(Sn1-xGex)S3 nanocrystals with tunable band gaps. AB - In this work, we show that compositionally controlled Cu2(Sn1-xGex)S3 nanocrystals can be successfully synthesized by the hot-injection method through careful tuning the Ge/(Sn+Ge) precursor ratio. The band gaps of the resultant nanocrystals are demonstrated to be linearly tuned from 1.45 to 2.33 eV by adjusting the composition parameter x of the Ge/(Sn+Ge) ratio from 0.0 to 1.0. The crystalline structures of the resultant NCs have been studied by the X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), select area electron diffraction (SAED), and Raman spectroscopy. A ligand exchange procedure is further performed to replace the native ligands on the surface of the NCs with sulfur ions. The photoresponsive behavior indicates the potential use of as-prepared Cu2(Sn1-xGex)S3 nanocrystals in solar energy conversion systems. The synthesis of compositionally controlled Cu2(Sn1-xGex)S3 nanocrystals reported herein provides a way for probing the effect of Ge inclusion in the Cu-Sn-S system thin films. PMID- 27398067 TI - Histopathological techniques for the diagnosis of combat-related invasive fungal wound infections. AB - BACKGROUND: Effective management of trauma-related invasive fungal wound infections (IFIs) depends on early diagnosis and timely initiation of treatment. We evaluated the utility of routine staining, histochemical stains and frozen section for fungal element identification. METHODS: A total of 383 histopathological specimens collected from 66 combat-injured United States military personnel with IFIs were independently reviewed by two pathologists. Both periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) stains were used on 74 specimens. The performance of the two special stains was compared against the finding of fungal elements via any histopathological method (ie, special stains or hematoxylin and eosin). In addition, the findings from frozen sections were compared against permanent sections. RESULTS: The GMS and PAS results were 84 % concordant (95 % confidence interval: 70 to 97 %). The false negative rate of fungal detection was 15 % for GMS and 44 % for PAS, suggesting that GMS was more sensitive; however, neither stain was statistically significantly superior for identifying fungal elements (p = 0.38). Moreover, 147 specimens had frozen sections performed, of which there was 87 % correlation with permanent sections (60 % sensitivity and 98 % specificity). In 27 permanent sections, corresponding cultures were available for comparison and 85 % concordance in general species identification was reported. CONCLUSIONS: The use of both stains does not have an added benefit for identifying fungal elements. Furthermore, while the high specificity of frozen section may aid in timely IFI diagnoses, it should not be used as a stand-alone method to guide therapy due to its low sensitivity. PMID- 27398068 TI - Prevalence of workplace violence in Northwest Ethiopia: a multivariate analysis. AB - BACKGROUND: Workplace violence has been acknowledged as a global problem, particularly in the health sector. However, there is scarce data on workplace violence among nurses in Ethiopia. The aim of this study was to assess the prevalence of workplace violence and associated factors among nurses in northwest Ethiopia. METHODS: Hospital based cross-sectional study design was employed in 386 nurses from April 1 - April 30, 2015. Data were collected through the use of self-administered questionnaire developed by the International Labor Office/International Council of Nurses/World Health Organization and Public Services International. To keep the quality of the data collection training was given to supervisors and data collectors. Piloting was done in Debark hospital two weeks before actual data collection to assess the tool's clarity and make amendments. The proposal was approved by the Institutional Review Board of University of Gondar prior to study commencement and a written consent was obtained from each study participant. RESULTS: The overall prevalence of workplace violence was 26.7 %. Exploratory logistic regression analyses suggested that age, number of staff in the same work shift, working in a male ward, history of workplace violence, and marital status were factors independently associated with workplace violence. CONCLUSION: The prevalence of workplace violence among nurses was high. Creating a prevention strategy involving different stakeholders is recommended. PMID- 27398069 TI - Nursing with Flare: The Operators of Light Therapy, c.1890-1940. AB - A much forgotten figure in the history of artificial and natural light therapies, the nurse played a central role in the administration of beneficial - and harmful - ultraviolet radiation in the treatment of skin diseases, tuberculosis and rickets, especially on child patients. As the primary operators of light therapy equipment, nurses specialised in this new and modern treatment, and both the therapy's successes and failures could be attributed to their skill, or lack thereof. This paper provides an introduction to the history of light therapy, especially phototherapy (artificial light therapy), during the early twentieth century in Britain, and to the 'invisible' technicians who contributed so much to its nascent reputation. PMID- 27398071 TI - Confronting Mortality: Narratives of Military Veterans Enrolled in Home Hospice Care. PMID- 27398070 TI - An extended cost-effectiveness analysis of schizophrenia treatment in India under universal public finance. AB - BACKGROUND: Schizophrenia remains a priority condition in mental health policy and service development because of its early onset, severity and consequences for affected individuals and households. AIMS AND METHODS: This paper reports on an 'extended' cost-effectiveness analysis (ECEA) for schizophrenia treatment in India, which seeks to evaluate through a modeling approach not only the costs and health effects of intervention but also the consequences of a policy of universal public finance (UPF) on health and financial outcomes across income quintiles. RESULTS: Using plausible values for input parameters, we conclude that health gains from UPF are concentrated among the poorest, whereas the non-health gains in the form of out-of-pocket private expenditures averted due to UPF are concentrated among the richest income quintiles. Value of insurance is the highest for the poorest quintile and declines with income. CONCLUSIONS: Universal public finance can play a crucial role in ameliorating the adverse economic and social consequences of schizophrenia and its treatment in resource-constrained settings where health insurance coverage is generally poor. This paper shows the potential distributional and financial risk protection effects of treating schizophrenia. PMID- 27398072 TI - An Examination of the Validity and Reliability of a Measure of Sexual Orientation Identity Exploration, Resolution, and Affirmation. AB - The processes of identity exploration and resolution are salient during adolescence and young adulthood, and awareness of sexual orientation identity, in particular, is heightened in early adolescence. Much of the research on sexual orientation identity development has focused on identity milestones (e.g., age of awareness and disclosure) or internalized homonegativity, rather than the developmental processes of exploration and resolution. Psychometric properties of the Sexual Orientation Identity Development Scale, which was adapted from a developmentally-informed measure of ethnic-racial identity, were evaluated in a sample of 382 Latina/o sexual minority adolescents and young adults. Results supported the reliability and validity of the adapted measure, as well as measurement equivalence across language (Spanish and English) and development (adolescence and young adulthood). PMID- 27398073 TI - Assessing Treatment Integrity in Alcohol Behavioral Couple Therapy. AB - OBJECTIVES: Alcohol Behavioral Couple Therapy (ABCT) is an efficacious treatment for alcohol use disorders. Coding treatment integrity can shed light on the active ingredients of ABCT, but there are no published studies of treatment integrity instruments for ABCT. The present study describes the development and initial reliability of the Treatment Integrity Rating System - Couples Version (C TIRS) for ABCT. METHODS: The C-TIRS was used to rate 284 first- and mid-treatment ABCT sessions of 188 couples in four randomized clinical trials. RESULTS: Average inter-rater reliability for distinguishing ratings between C-TIRS items was fair to-good for quantity items (intraclass correlation [ICC] = 0.64) and poor-to-fair for quality items (ICC = 0.41). Five C-TIRS subscales were defined a priori to measure treatment components involving cognitive-behavioral therapy, spouse involvement, couple therapy, common therapeutic factors, and overall adherence to the treatment protocol and had adequate internal reliability (alpha = 0.74-0.89). Inter-rater reliability was fair to good on seven of ten scales but poor on three scales (ICC range = 0.17-0.72). CONCLUSIONS: The C-TIRS was designed to provide information about quantity and quality of the delivery of ABCT components; however, further refinement of the C-TIRS is warranted before it should be used in frontline practice. Clinical implications and recommendations for future research are discussed. PMID- 27398074 TI - Mechanistic Role of Emotion Regulation in the PTSD and Alcohol Association. AB - OBJECTIVE: Posttraumatic Stress Disorder (PTSD) has been linked to problematic alcohol use. Those with PTSD have greater difficulty regulating emotions, which may help to explain the PTSD-drinking co-occurrence. However, emotion regulation as a mediator of PTSD-alcohol associations has been limited. In the present study, we examined this association. METHOD: College students (N = 466, Mage = 19.5, 53% female) were assessed for PTSD by structured clinical interview, and were categorized into three groups: those who had not experienced a significant trauma (No Trauma, n = 182), those who had experienced a significant trauma but did not have current PTSD symptoms (Trauma Only, n = 171), and those with significant trauma and with current PTSD (partial or full; PTSD, n = 113). Alcohol use over the past six months and emotion regulation were assessed via self-report (DDQ; Collins, Parks, & Marlatt, 1985; DERS; Gratz & Roemer, 2004). RESULTS: Findings revealed that those with trauma and clinically significant PTSD reported greater difficulty with emotion regulation than those who had not been exposed to trauma, which in turn significantly predicted alcohol use. This mediating effect was not found in those with trauma exposure alone, suggesting an important role for PTSD in this pathway. Findings also indicated that the ability to control emotion-based impulses is a particularly relevant mediating facet of emotion regulation. CONCLUSION: These results implicate emotion regulation as a potential explanatory link between PTSD and alcohol use, lending further support to the inclusion of emotion regulation training in PTSD treatment. PMID- 27398075 TI - The utility of polarized heliospheric imaging for space weather monitoring. AB - A polarizing heliospheric imager is a critical next generation tool for space weather monitoring and prediction. Heliospheric imagers can track coronal mass ejections (CMEs) as they cross the solar system, using sunlight scattered by electrons in the CME. This tracking has been demonstrated to improve the forecasting of impact probability and arrival time for Earth-directed CMEs. Polarized imaging allows locating CMEs in three dimensions from a single vantage point. Recent advances in heliospheric imaging have demonstrated that a polarized imager is feasible with current component technology.Developing this technology to a high technology readiness level is critical for space weather relevant imaging from either a near-Earth or deep-space mission. In this primarily technical review, we developpreliminary hardware requirements for a space weather polarizing heliospheric imager system and outline possible ways to flight qualify and ultimately deploy the technology operationally on upcoming specific missions. We consider deployment as an instrument on NOAA's Deep Space Climate Observatory follow-on near the Sun-Earth L1 Lagrange point, as a stand-alone constellation of smallsats in low Earth orbit, or as an instrument located at the Sun-Earth L5 Lagrange point. The critical first step is the demonstration of the technology, in either a science or prototype operational mission context. PMID- 27398076 TI - Spacecraft surface charging within geosynchronous orbit observed by the Van Allen Probes. AB - Using the Helium Oxygen Proton Electron (HOPE) and Electric Field and Waves (EFW) instruments from the Van Allen Probes, we explored the relationship between electron energy fluxes in the eV and keV ranges and spacecraft surface charging. We present statistical results on spacecraft charging within geosynchronous orbit by L and MLT. An algorithm to extract the H+ charging line in the HOPE instrument data was developed to better explore intense charging events. Also, this study explored how spacecraft potential relates to electron number density, electron pressure, electron temperature, thermal electron current, and low-energy ion density between 1 and 210 eV. It is demonstrated that it is imperative to use both EFW potential measurements and the HOPE instrument ion charging line for examining times of extreme spacecraft charging of the Van Allen Probes. The results of this study show that elevated electron energy fluxes and high-electron pressures are present during times of spacecraft charging but these same conditions may also occur during noncharging times. We also show noneclipse significant negative charging events on the Van Allen Probes. PMID- 27398077 TI - The Bionanoprobe: Synchrotron-based Hard X-ray Fluorescence Microscopy for 2D/3D Trace Element Mapping. PMID- 27398078 TI - Epidemiology Without Biology: False Paradigms, Unfounded Assumptions, and Specious Statistics in Radiation Science (with Commentaries by Inge Schmitz Feuerhake and Christopher Busby and a Reply by the Authors). AB - Radiation science is dominated by a paradigm based on an assumption without empirical foundation. Known as the linear no-threshold (LNT) hypothesis, it holds that all ionizing radiation is harmful no matter how low the dose or dose rate. Epidemiological studies that claim to confirm LNT either neglect experimental and/or observational discoveries at the cellular, tissue, and organismal levels, or mention them only to distort or dismiss them. The appearance of validity in these studies rests on circular reasoning, cherry picking, faulty experimental design, and/or misleading inferences from weak statistical evidence. In contrast, studies based on biological discoveries demonstrate the reality of hormesis: the stimulation of biological responses that defend the organism against damage from environmental agents. Normal metabolic processes are far more damaging than all but the most extreme exposures to radiation. However, evolution has provided all extant plants and animals with defenses that repair such damage or remove the damaged cells, conferring on the organism even greater ability to defend against subsequent damage. Editors of medical journals now admit that perhaps half of the scientific literature may be untrue. Radiation science falls into that category. Belief in LNT informs the practice of radiology, radiation regulatory policies, and popular culture through the media. The result is mass radiophobia and harmful outcomes, including forced relocations of populations near nuclear power plant accidents, reluctance to avail oneself of needed medical imaging studies, and aversion to nuclear energy-all unwarranted and all harmful to millions of people. PMID- 27398079 TI - Metabolic analysis of the response of Pseudomonas putida DOT-T1E strains to toluene using Fourier transform infrared spectroscopy and gas chromatography mass spectrometry. AB - INTRODUCTION: An exceptionally interesting stress response of Pseudomonas putida strains to toxic substances is the induction of efflux pumps that remove toxic chemical substances from the bacterial cell out to the external environment. To exploit these microorganisms to their full potential a deeper understanding of the interactions between the bacteria and organic solvents is required. Thus, this study focuses on investigation of metabolic changes in P. putida upon exposure to toluene. OBJECTIVE: Investigate observable metabolic alterations during interactions of three strains of P. putida (DOT-T1E, and its mutants DOT T1E-PS28 and DOT-T1E-18) with the aromatic hydrocarbon toluene. METHODS: The growth profiles were measured by taking optical density (OD) measurement at 660 nm (OD660) at various time points during incubation. For fingerprinting analysis, Fourier-transform infrared (FT-IR) spectroscopy was used to investigate any phenotypic changes resulting from exposure to toluene. Metabolic profiling analysis was performed using gas chromatography-mass spectrometry (GC-MS). Principal component-discriminant function analysis (PC-DFA) was applied to the FT IR data while multiblock principal component analysis (MB-PCA) and N-way analysis of variance (N-way ANOVA) were applied to the GC-MS data. RESULTS: The growth profiles demonstrated the effect of toluene on bacterial cultures and the results suggest that the mutant P. putida DOT-T1E-18 was more sensitive (significantly affected) to toluene compared to the other two strains. PC-DFA on FT-IR data demonstrated the differentiation between different conditions of toluene on bacterial cells, which indicated phenotypic changes associated with the presence of the solvent within the cell. Fifteen metabolites associated with this phenotypic change, in P. putida due to exposure to solvent, were from central metabolic pathways. Investigation of MB-PCA loading plots and N-way ANOVA for condition | strain * time blocking (dosage of toluene) suggested ornithine as the most significant compound that increased upon solvent exposure. CONCLUSION: The combination of metabolic fingerprinting and profiling with suitable multivariate analysis revealed some interesting leads for understanding the mechanism of Pseudomonas strains response to organic solvent exposure. PMID- 27398080 TI - Metabolomics meets functional assays: coupling LC-MS and microfluidic cell-based receptor-ligand analyses. AB - INTRODUCTION: Metabolomics has become a valuable tool in many research areas. However, generating metabolomics-based biochemical profiles without any related bioactivity is only of indirect value in understanding a biological process. Therefore, metabolomics research could greatly benefit from tools that directly determine the bioactivity of the detected compounds. OBJECTIVE: We aimed to combine LC-MS metabolomics with a cell based receptor assay. This combination could increase the understanding of biological processes and may provide novel opportunities for functional metabolomics. METHODS: We developed a flow through biosensor with human cells expressing both the TRPV1, a calcium ion channel which responds to capsaicin, and the fluorescent intracellular calcium ion reporter, YC3.6. We have analysed three contrasting Capsicum varieties. Two were selected with contrasting degrees of spiciness for characterization by HPLC coupled to high mass resolution MS. Subsequently, the biosensor was then used to link individual pepper compounds with TRPV1 activity. RESULTS: Among the compounds in the crude pepper fruit extracts, we confirmed capsaicin and also identified both nordihydrocapsaicin and dihydrocapsaicin as true agonists of the TRPV1 receptor. Furthermore, the biosensor was able to detect receptor activity in extracts of both Capsicum fruits as well as a commercial product. Sensitivity of the biosensor to this commercial product was similar to the sensory threshold of a human sensory panel. CONCLUSION: Our results demonstrate that the TRPV1 biosensor is suitable for detecting bioactive metabolites. Novel opportunities may lie in the development of a continuous functional assay, where the biosensor is directly coupled to the LC-MS. PMID- 27398081 TI - Scorpion incidents, misidentification cases and possible implications for the final interpretation of results. AB - The aim of this contribution is to bring general information on the classification and in particular on the specific identification of scorpion species dangerous to humans. Several generic groups are taken into consideration, but the Neotropical genus Tityus C. L. Koch, 1836 is used as a major example. The content of this paper is mostly addressed to non-specialists whose research embraces scorpions in several fields such as venom toxins and public health. Although efforts have been made in the last 20 years to create better links between 'true scorpion experts' and non-specialists who use scorpions in their research, such exchanges had never led to a consensus among those different branches of biological and medical research. Consequently, many cases of species misidentification and even more serious errors concerning scorpion classification/identification are often present in the specialized literature. In conclusion, it is suggested here that the frequent cases of misidentification observed in several reports may induce mistakes in the final interpretation of results, leading only to more inefficacity in the treatment of problems caused by infamous scorpion species. PMID- 27398082 TI - Facial reconstruction with a unique osteomyocutaneous DCIA perforator flap variant: a case report. AB - BACKGROUND: Anatomical variance of the deep circumflex iliac artery is of high clinical value in facial reconstruction using a deep circumflex iliac artery perforator (DCIAP) flap. METHODS: We present the case of a 76-year-old woman treated with an osteomyocutaneous DCIAP flap variant for facial reconstruction. We also review here the literature on DCIA perforator flaps and the different anatomical variances, which might bring clinical benefits. RESULTS: The observed anatomy in our patient offered the possibility to raise a free flap variant with high mobility of a large skin paddle and a long vascular pedicle combined with a variable osteomuscular portion. CONCLUSION: The characteristics of the flap thus raised help overcome the disadvantages of the conventional DCIAP flap and offer excellent options for facial reconstruction. PMID- 27398083 TI - Design of Nanoparticle-Based Carriers for Targeted Drug Delivery. AB - Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this article, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting and physical targeting), compare methods of action, advantages, limitations, and the current stage of research. For the most commonly used nanoparticle carriers, fabrication methods are also reviewed. This is followed by a review of computational simulations and models on nanoparticle-based drug delivery. PMID- 27398084 TI - Disentangling proactive and reactive aggression in children using self-report. AB - The distinction between proactive and reactive functions of aggression is one of the most common divisions when investigating aggression among children and adolescents. To date, self-report is the least used measurement, despite existing literature supporting the view that the best informant regarding internal processes and motives are children themselves. The main aim of this study was to examine the construct and concurrent validity of a new self-report questionnaire, which aims to disentangle acts of reactive vs. proactive aggression that are most common within the daily lives of children. We examined the self-report measure among 578 children (313 girls, 265 boys, mean age 11 years, range 9-13 years). Most children (90% boys; 85% girls) reported at least one act of aggression over the last four weeks. Furthermore, the outcomes support the two-factor structure (reactive and proactive aggression) and the questionnaire showed good concurrent and discriminant validity with measures for emotional and social functioning. This study validates the use of the self-report instrument for reactive and proactive aggression and demonstrates that children can successfully distinguish between their own motives for reactive and proactive forms of aggressive behaviours. PMID- 27398085 TI - A Missing Element in Migration Theories. AB - From the mid-1950s through the mid1980s, migration between Mexico and the United States constituted a stable system whose contours were shaped by social and economic conditions well-theorized by prevailing models of migration. It evolved as a mostly circular movement of male workers going to a handful of U.S. states in response to changing conditions of labor supply and demand north and south of the border, relative wages prevailing in each nation, market failures and structural economic changes in Mexico, and the expansion of migrant networks following processes specified by neoclassical economics, segmented labor market theory, the new economics of labor migration, social capital theory, world systems theory, and theoretical models of state behavior. After 1986, however, the migration system was radically transformed, with the net rate of migration increasing sharply as movement shifted from a circular flow of male workers going a limited set of destinations to a nationwide population of settled families. This transformation stemmed from a dynamic process that occurred in the public arena to bring about an unprecedented militarization of the Mexico-U.S. border, and not because of shifts in social, economic, or political factors specified in prevailing theories. In this paper I draw on earlier work to describe that dynamic process and demonstrate its consequences, underscoring the need for greater theoretical attention to the self-interested actions of politicians, pundits, and bureaucrats who benefit from the social construction and political manufacture of immigration crises when none really exist. PMID- 27398086 TI - Redox modulation of cellular stress response and lipoxin A4 expression by Hericium Erinaceus in rat brain: relevance to Alzheimer's disease pathogenesis. AB - BACKGROUND: There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. RESULTS: Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. CONCLUSIONS: Conceivably, activation of LXA4 signaling and modulation of stress responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage. PMID- 27398087 TI - Determinants of time to antiretroviral treatment initiation and subsequent mortality on treatment in a cohort in rural northern Malawi. AB - BACKGROUND: To optimise care HIV patients need to be promptly initiated on antiretroviral therapy (ART) and subsequently retained on treatment. In this study we report on the interval between enrolment and treatment initiation, and investigate subsequent attrition and mortality of patients on ART at a rural clinic in Malawi. METHODS: HIV-positive individuals were recruited to a cohort study between January 2008 and August 2011 at Chilumba Rural Hospital (CRH). Outcomes were ascertained, up to 7 years after enrolment, through follow-up and by linkage to ART registers and the Karonga Health and Demographic Surveillance System (KHDSS). Kaplan-Meier methods and Cox regression were used to examine ART initiation after enrolment, mortality after ART initiation, and attrition after ART initiation. RESULTS: Of the 617 individuals recruited, 523 initiated ART between January 2008 and January 2015. Median time from HIV testing to commencement of ART was 59 days (IQR: 10-330). By a year after enrolment 74.2 % (95 % CI 70.6-77.7 %) had initiated ART. Baseline clinical data at ART initiation and data on attrition was only available for the 438 individuals who initiated ART during active follow-up, between January 2008 and August 2011. Of these individuals, 6 were missing Ministry of Health numbers, leaving 432 included in analyses of attrition and mortality. At 4 years after ART initiation 71.3 % (95 % CI 65.7-76.2 %) of these patients were retained on treatment at the CRH and 17.2 % (95 % CI 13.8-21.4 %) had died. Participants who had a lower CD4 count at enrolment (<=350 cells/MUl), enrolled in 2008, or tested for HIV at the CRH rather than through serosurveys, initiated treatment faster. Once on treatment, mortality rates were higher in patients who were HIV tested at the CRH, male, older (>=35 years), missing a CD4 count, or underweight (BMI < 18.5) at ART initiation. CONCLUSIONS: Through linkage to the KHDSS and ART registers it was possible to continue follow-up beyond the end of the initial cohort study. Annual mortality after ART initiation remained considerable over a period of 4 years. Greater access to HIV and CD4 testing alongside initiation at higher CD4 counts, as planned in the test and treat strategy, could reduce this mortality. PMID- 27398088 TI - Conservation of genetic uniqueness of populations may increase extinction likelihood of endangered species: the case of Australian mammals. AB - BACKGROUND: As increasingly fragmented and isolated populations of threatened species become subjected to climate change, invasive species and other stressors, there is an urgent need to consider adaptive potential when making conservation decisions rather than focussing on past processes. In many cases, populations identified as unique and currently managed separately suffer increased risk of extinction through demographic and genetic processes. Other populations currently not at risk are likely to be on a trajectory where declines in population size and fitness soon appear inevitable. RESULTS: Using datasets from natural Australian mammal populations, we show that drift processes are likely to be driving uniqueness in populations of many threatened species as a result of small population size and fragmentation. Conserving and managing such remnant populations separately will therefore often decrease their adaptive potential and increase species extinction risk. CONCLUSIONS: These results highlight the need for a paradigm shift in conservation biology practise; strategies need to focus on the preservation of genetic diversity at the species level, rather than population, subspecies or evolutionary significant unit. The introduction of new genetic variants into populations through in situ translocation needs to be considered more broadly in conservation programs as a way of decreasing extinction risk by increasing neutral genetic diversity which may increase the adaptive potential of populations if adaptive variation is also increased. PMID- 27398089 TI - A Bayesian inference method for the analysis of transcriptional regulatory networks in metagenomic data. AB - BACKGROUND: Metagenomics enables the analysis of bacterial population composition and the study of emergent population features, such as shared metabolic pathways. Recently, we have shown that metagenomics datasets can be leveraged to characterize population-wide transcriptional regulatory networks, or meta regulons, providing insights into how bacterial populations respond collectively to specific triggers. Here we formalize a Bayesian inference framework to analyze the composition of transcriptional regulatory networks in metagenomes by determining the probability of regulation of orthologous gene sequences. We assess the performance of this approach on synthetic datasets and we validate it by analyzing the copper-homeostasis network of Firmicutes species in the human gut microbiome. RESULTS: Assessment on synthetic datasets shows that our method provides a robust and interpretable metric for assessing putative regulation by a transcription factor on sets of promoter sequences mapping to an orthologous gene cluster. The inference framework integrates the regulatory contribution of secondary sites and can discern false positives arising from multiple instances of a clonal sequence. Posterior probabilities for orthologous gene clusters decline sharply when less than 20 % of mapped promoters have binding sites, but we introduce a sensitivity adjustment procedure to speed up computation that enhances regulation assessment in heterogeneous ortholog clusters. Analysis of the copper-homeostasis regulon governed by CsoR in the human gut microbiome Firmicutes reveals that CsoR controls itself and copper-translocating P-type ATPases, but not CopZ-type copper chaperones. Our analysis also indicates that CsoR frequently targets promoters with dual CsoR-binding sites, suggesting that it exploits higher-order binding conformations to fine-tune its activity. CONCLUSIONS: We introduce and validate a method for the analysis of transcriptional regulatory networks from metagenomic data that enables inference of meta-regulons in a systematic and interpretable way. Validation of this method on the CsoR meta-regulon of gut microbiome Firmicutes illustrates the usefulness of the approach, revealing novel properties of the copper-homeostasis network in poorly characterized bacterial species and putting forward evidence of new mechanisms of DNA binding for this transcriptional regulator. Our approach will enable the comparative analysis of regulatory networks across metagenomes, yielding novel insights into the evolution of transcriptional regulatory networks. PMID- 27398090 TI - Using fragmentation to assess degradation of forest edges in Democratic Republic of Congo. AB - BACKGROUND: Recent studies have shown that fragmentation is an increasing threat to global forests, which has major impacts on biodiversity and the important ecosystem services provided by forested landscapes. Several tools have been developed to evaluate global patterns of fragmentation, which have potential applications for REDD+. We study how canopy height and above ground biomass (AGB) change across several categories of forest edges determined by fragmentation analysis. We use Democratic Republic of Congo (DRC) as an example. RESULTS: An analysis of variance of different edge widths and airborne estimated canopy height found that canopy heights were significantly different in forest edges at a distance of 100 m from the nonforest edge. Biomass was significantly different between fragmentation classes at an edge distance of 300 m. Core forest types were found to have significantly higher canopy height and greater AGB than forest edges and patches, where height and biomass decrease significantly as the level of fragmentation increases. A change analysis shows that deforestation and degradation are increasing over time and biomass loss associated with degradation account for at least one quarter of total loss. We estimate that about 80 % of primary forests are intact, which decreases 3.5 % over the 15 year study period, as primary forest is either deforested or transitioned to forest edge. While the carbon loss per hectare is lower than that of deforestation, degradation potentially affects up to three times more area than deforestation alone. CONCLUSIONS: When defining forest degradation by decreased biomass without any loss in forest area, assessing transitions of core forest to edges over time can contribute an important element to REDD+MRV systems. The estimation of changes between different forest fragmentation types and their associated biomass loss can provide an estimate of degradation carbon emission factors. Forest degradation and emissions due to fragmentation are often underestimated and should comprise an essential component of MRV systems. PMID- 27398091 TI - Comparison of calculation methods for estimating annual carbon stock change in German forests under forest management in the German greenhouse gas inventory. AB - BACKGROUND: The German greenhouse gas inventory in the land use change sector strongly depends on national forest inventory data. As these data were collected periodically 1987, 2002, 2008 and 2012, the time series on emissions show several "jumps" due to biomass stock change, especially between 2001 and 2002 and between 2007 and 2008 while within the periods the emissions seem to be constant due to the application of periodical average emission factors. This does not reflect inter-annual variability in the time series, which would be assumed as the drivers for the carbon stock changes fluctuate between the years. Therefore additional data, which is available on annual basis, should be introduced into the calculations of the emissions inventories in order to get more plausible time series. RESULTS: This article explores the possibility of introducing an annual rather than periodical approach to calculating emission factors with the given data and thus smoothing the trajectory of time series for emissions from forest biomass. Two approaches are introduced to estimate annual changes derived from periodic data: the so-called logging factor method and the growth factor method. The logging factor method incorporates annual logging data to project annual values from periodic values. This is less complex to implement than the growth factor method, which additionally adds growth data into the calculations. CONCLUSION: Calculation of the input variables is based on sound statistical methodologies and periodically collected data that cannot be altered. Thus a discontinuous trajectory of the emissions over time remains, even after the adjustments. It is intended to adopt this approach in the German greenhouse gas reporting in order to meet the request for annually adjusted values. PMID- 27398093 TI - Transmissible cancers, are they more common than thought? PMID- 27398092 TI - Role of magnesium ions in the reaction mechanism at the interface between Tm1631 protein and its DNA ligand. AB - A protein, Tm1631 from the hyperthermophilic organism Thermotoga maritima belongs to a domain of unknown function protein family. It was predicted that Tm1631 binds with the DNA and that the Tm1631-DNA complex is an endonuclease repair system with a DNA repair function (Konc et al. PLoS Comput Biol 9(11): e1003341, 2013). We observed that the severely bent, strained DNA binds to the protein for the entire 90 ns of classical molecular dynamics (MD) performed; we could observe no significant changes in the most distorted region of the DNA, where the cleavage of phosphodiester bond occurs. In this article, we modeled the reaction mechanism at the interface between Tm1631 and its proposed ligand, the DNA molecule, focusing on cleavage of the phosphodiester bond. After addition of two Mg(2+) ions to the reaction center and extension of classical MD by 50 ns (totaling 140 ns), the DNA ligand stayed bolted to the protein. Results from density functional theory quantum mechanics/molecular mechanics (QM/MM) calculations suggest that the reaction is analogous to known endonuclease mechanisms: an enzyme reaction mechanism with two Mg(2+) ions in the reaction center and a pentacovalent intermediate. The minimum energy pathway profile shows that the phosphodiester bond cleavage step of the reaction is kinetically controlled and not thermodynamically because of a lack of any energy barrier above the accuracy of the energy profile calculation. The role of ions is shown by comparing the results with the reaction mechanisms in the absence of the Mg(2+) ions where there is a significantly higher reaction barrier than in the presence of the Mg(2+) ions.Graphical abstractA protein, Tm1631 from the hyperthermophilic organism Thermotoga maritima belongs to a domain of unknown function protein family. We modeled the reaction mechanism at the interface between Tm1631 and its proposed ligand, the DNA molecule, focusing on cleavage of the phosphodiester bond. PMID- 27398094 TI - The GH51 alpha-l-arabinofuranosidase from Paenibacillus sp. THS1 is multifunctional, hydrolyzing main-chain and side-chain glycosidic bonds in heteroxylans. AB - BACKGROUND: Conceptually, multi-functional enzymes are attractive because in the case of complex polymer hydrolysis having two or more activities defined by a single enzyme offers the possibility of synergy and reduced enzyme cocktail complexity. Nevertheless, multi-functional enzymes are quite rare and are generally multi-domain assemblies with each activity being defined by a separate protein module. However, a recent report described a GH51 arabinofuranosidase from Alicyclobacillus sp. A4 that displays both alpha-l-arabinofuranosidase and beta-d-xylanase activities, which are defined by a single active site. Following on from this, we describe in detail another multi-functional GH51 arabinofuranosidase and discuss the molecular basis of multifunctionality. RESULTS: THSAbf is a GH51 alpha-l-arabinofuranosidase. Characterization revealed that THSAbf is active up to 75 degrees C, stable at 60 degrees C and active over a broad pH range (4-7). THSAbf preferentially releases para-nitrophenyl from the l-arabinofuranoside (k cat/K M = 1050 s(-1) mM(-1)) and to some extent from d galactofuranoside and d-xyloside. THSAbf is active on 4-O-methylglucuronoxylans from birch and beechwood (10.8 and 14.4 U mg(-1), respectively) and on sugar beet branched and linear arabinans (1.1 +/- 0.24 and 1.8 +/- 0.1 U mg(-1)). Further investigation revealed that like the Alicyclobacillus sp. A4 alpha-l arabinofuranosidase, THSAbf also displays endo-xylanase activity, cleaving beta 1,4 bonds in heteroxylans. The optimum pH for THASAbf activity is substrate dependent, but ablation of the catalytic nucleophile caused a general loss of activity, indicating the involvement of a single active center. Combining the alpha-l-arabinofuranosidase with a GH11 endoxylanase did not procure synergy. The molecular modeling of THSAbf revealed a wide active site cleft and clues to explain multi-functionality. CONCLUSION: The discovery of single active site, multifunctional enzymes such as THSAbf opens up exciting avenues for enzyme engineering and the development of new biomass-degrading cocktails that could considerably reduce enzyme production costs. PMID- 27398095 TI - Chromatin variation associated with liver metabolism is mediated by transposable elements. AB - BACKGROUND: Functional regulatory regions in eukaryotic genomes are characterized by the disruption of nucleosomes leading to accessible chromatin. The modulation of chromatin accessibility is one of the key mediators of transcriptional regulation, and variation in chromatin accessibility across individuals has been linked to complex traits and disease susceptibility. While mechanisms responsible for chromatin variation across individuals have been investigated, the overwhelming majority of chromatin variation remains unexplained. Furthermore, the processes through which the variation of chromatin accessibility contributes to phenotypic diversity remain poorly understood. RESULTS: We profiled chromatin accessibility in liver from seven strains of mice with phenotypic diversity in response to a high-fat/high-sucrose (HF/HS) diet and identified reproducible chromatin variation across the individuals. We found that sites of variable chromatin accessibility were more likely to coincide with particular classes of transposable elements (TEs) than sites with common chromatin signatures. Evolutionarily younger long interspersed nuclear elements (LINEs) are particularly likely to harbor variable chromatin sites. These younger LINEs are enriched for binding sites of immune-associated transcription factors, whereas older LINEs are enriched for liver-specific transcription factors. Genomic region enrichment analysis indicates that variable chromatin sites at TEs may function to regulate liver metabolic pathways. CRISPR-Cas9 deletion of a number of variable chromatin sites at TEs altered expression of nearby metabolic genes. Finally, we show that polymorphism of TEs and differential DNA methylation at TEs can both influence chromatin variation. CONCLUSIONS: Our results demonstrate that specific classes of TEs show variable chromatin accessibility across strains of mice that display phenotypic diversity in response to a HF/HS diet. These results indicate that chromatin variation at TEs is an important contributor to phenotypic variation among populations. PMID- 27398096 TI - The Glasgow-Maastricht foot model, evaluation of a 26 segment kinematic model of the foot. AB - BACKGROUND: Accurately measuring of intrinsic foot kinematics using skin mounted markers is difficult, limited in part by the physical dimensions of the foot. Existing kinematic foot models solve this problem by combining multiple bones into idealized rigid segments. This study presents a novel foot model that allows the motion of the 26 bones to be individually estimated via a combination of partial joint constraints and coupling the motion of separate joints using kinematic rhythms. METHODS: Segmented CT data from one healthy subject was used to create a template Glasgow-Maastricht foot model (GM-model). Following this, the template was scaled to produce subject-specific models for five additional healthy participants using a surface scan of the foot and ankle. Forty-three skin mounted markers, mainly positioned around the foot and ankle, were used to capture the stance phase of the right foot of the six healthy participants during walking. The GM-model was then applied to calculate the intrinsic foot kinematics. RESULTS: Distinct motion patterns where found for all joints. The variability in outcome depended on the location of the joint, with reasonable results for sagittal plane motions and poor results for transverse plane motions. CONCLUSIONS: The results of the GM-model were comparable with existing literature, including bone pin studies, with respect to the range of motion, motion pattern and timing of the motion in the studied joints. This novel model is the most complete kinematic model to date. Further evaluation of the model is warranted. PMID- 27398098 TI - Cheminformatics analysis of the AR agonist and antagonist datasets in PubChem. AB - BACKGROUND: As one of the largest publicly accessible databases for hosting chemical structures and biological activities, PubChem has been processing bioassay submissions from the community since 2004. With the increase in volume for the deposited data in PubChem, the diversity and wealth of information content also grows. Recently, the Tox21 program, has deposited a series of pairwise data in PubChem regarding to different mechanism of actions (MOA), such as androgen receptor (AR) agonist and antagonist datasets, to study cell toxicity. To the best of our knowledge, little work has been reported from cheminformatics study for these especially pairwise datasets, which may provide insight into the mechanism of actions of the compounds and relationship between chemical structures and functions, as well as guidance for lead compound selection and optimization. Thus, to fill the gap, we performed a comprehensive cheminformatics analysis, including scaffold analysis, matched molecular pair (MMP) analysis as well as activity cliff analysis to investigate the structural characteristics and discontinued structure-activity relationship of the individual dataset (i.e., AR agonist dataset or AR antagonist dataset) and the combined dataset (i.e., the common compounds between the AR agonist and antagonist datasets). RESULTS: Scaffolds associated only with potential agonists or antagonists were identified. MMP-based activity cliffs, as well as a small group of compounds with dual MOA reported were recognized and analyzed. Moreover, MOA-cliff, a novel concept, was proposed to indicate one pair of structurally similar molecules which exhibit opposite MOA. CONCLUSIONS: Cheminformatics methods were successfully applied to the pairwise AR datasets and the identified molecular scaffold characteristics, MMPs as well as activity cliffs might provide useful information when designing new lead compounds for the androgen receptor. PMID- 27398097 TI - Interpreting outcome following foot surgery in people with rheumatoid arthritis. AB - BACKGROUND: Foot surgery is common in RA but the current lack of understanding of how patients interpret outcomes inhibits evaluation of procedures in clinical and research settings. This study aimed to explore which factors are important to people with RA when they evaluate the outcome of foot and ankle surgery. METHODS AND RESULTS: Semi structured interviews with 11 RA participants who had mixed experiences of foot surgery were conducted and analysed using thematic analysis. Responses showed that while participants interpreted surgical outcome in respect to a multitude of factors, five major themes emerged: functional ability, participation, appearance of feet and footwear, surgeons' opinion, and pain. Participants interpreted levels of physical function in light of other aspects of their disease, reflecting on relative change from their preoperative state more than absolute levels of ability. Appearance was important to almost all participants: physical appearance, foot shape, and footwear were closely interlinked, yet participants saw these as distinct concepts and frequently entered into a defensive repertoire, feeling the need to justify that their perception of outcome was not about cosmesis. Surgeons' post-operative evaluation of the procedure was highly influential and made a lasting impression, irrespective of how the outcome compared to the participants' initial goals. Whilst pain was important to almost all participants, it had the greatest impact upon them when it interfered with their ability to undertake valued activities. CONCLUSIONS: People with RA interpret the outcome of foot surgery using multiple interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than anticipated. These factors can help clinicians in discussing surgical options in patients. PMID- 27398099 TI - Assessing Quality of Answers to a Global Subjective Well-being Question Through Response Times. AB - Many large-scale surveys measure subjective well-being (SWB) through a single survey item. This paper takes advantages of response time data to explore the relation between time taken to answer a single SWB item and the reliability and validity of answers to this SWB item. We found that reliability and validity of answers to the SWB item are low for fast respondents aged 70 and above and slow respondents between the age of 50 and 70. The findings indicate that longer time spent answering the single SWB item is associated with data of lower quality for respondents aged between 50 and 70, but data of higher quality for respondents aged 70 and above. This paper speaks to the importance of capitalizing response times that are readily available from computerized interviews to evaluate answers provided by respondents and calls for survey researchers' attention to differences in time taken to answer a survey question across respondent subgroups. PMID- 27398101 TI - How we do: optimizing bone marrow biopsy logistics for sign-out within 2 days. AB - Since the introduction of fast diagnostic tracks in many areas of oncology, the traditional processing of bone marrow biopsies (BMB), requiring either resin embedding or lengthy fixation and decalcification, is due to an upgrade. Thanks to a growing number of new commercially available tissue processors, microwave enhanced processing is becoming a standard tool in the pathology laboratory, allowing rapid fixation and decalcification of BMB with preserved morphology and antigens. In this short report, we describe the use of a commercially available EDTA-based decalcification fluid (USEDECALC, Medite, Orlando, USA) in combination with the LOGOS J (Milestone, Bergamo, Italy), a closed microwave-enhanced tissue processor, for overnight fixation, decalcification, and paraffin impregnation of the BMB. This allows next-day reporting without impaired morphology or immunohistochemistry, and even improved DNA quality of the BMB. PMID- 27398100 TI - Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context. AB - Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic (TCP) or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that extracellular matrix cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF like growth factor (HB-EGF). This study suggests that rBM gels can be used to induce in vitro lesion formation in order to identify soluble factors that influence proliferation and invasion. PMID- 27398102 TI - New developments in the pathology of malignant lymphoma. A review of the literature published from January-April 2016. PMID- 27398104 TI - Prevalence of Traumatic Dental Injuries in Patients Attending University of Alberta Emergency Clinic. AB - OBJECTIVES: This study evaluated the prevalence of dental trauma for patients attending the emergency dental clinic at the University of Alberta Hospital between 2006-2009. Patients' examination and treatment charts were reviewed. METHODS: Total number of patients' charts was 1893.The prevalence of different types of trauma was 6.4 % of the total cases (117 patients). Trauma cases were identified according to Ellis classification and as modified by Holland et al., 1988. RESULTS: Logistic statistical model showed that 21.7% were Ellis class I trauma, 16.7% were Ellis class II trauma, and 6.7% were Ellis class III. In addition, 11.7 % presented with avulsion, 7.5 % presented with dentoalveolar fracture and 7.5% presented with sublaxation. Also, 17.55 % presented with tooth displacement within the alveolar bone, 3.3 % presented with crown fracture with no pulp involvement, 4.16 % presented with crown fracture with pulp involvement and 3.3 % presented with root fracture. In conclusion, the general prevalence of dentoalveolar trauma in patients attending the emergency clinic at the University of Alberta is less than other reported percentages in Canada or other countries. PMID- 27398103 TI - Quality of Life and Self-Determination: Youth with Chronic Health Conditions Make the Connection. AB - While optimizing quality of life (QOL) is a key goal of rehabilitation care, no previous study has reported on what 'QOL' means to youth with chronic health conditions. In addition, no qualitative studies have explored the relationship between QOL and self-determination (SD). Objectives of this qualitative study were to examine: what the terms 'quality of life' and 'self-determination' mean to youth with chronic conditions; the factors these youth think are linked with these concepts; the relationship they see between concepts, the types of future goals youth have and how they view the connection between their SD and these goals. A descriptive methodology was used. A purposive sample of 15 youth aged 15 to 20 years was obtained. Youth had cerebral palsy, a central nervous system disorder, or autism spectrum disorder. Semi-structured interviews were conducted first, followed by a focus group. Line-by-line coding of transcripts was completed, codes were collapsed into categories, and themes identified. Participants viewed QOL as an overarching personal evaluation of their life, and used terms such as satisfaction and happiness to describe the concept. Factors related to QOL included: 'relationships', 'supportive environments', 'doing things', 'personal growth and moving forward', and 'understanding of self/acceptance of disability'. Participants described SD in such terms as confidence and motivation. Contributors to SD were: 'personal strengths', 'interdependence', and 'functional independence'. SD was considered important to QOL. Youth goals were reflective of the goals of most adolescents. They identified the importance of having key goals that were of personal interest to them. This study adds consumer-based information to the debate over the meaning of QOL. Service providers and decision makers should be aware of the factors that youth feel impact their QOL and SD, the importance of SD to youth QOL, and of SD to future goals, and consider this information when tailoring therapeutic interventions. PMID- 27398105 TI - Accuracy of Panoramic Radiograph in Assessment of the Relationship Between Mandibular Canal and Impacted Third Molars. AB - BACKGROUND: The relationship between impacted mandibular third molar and mandibular canal is important for removal of this tooth. Panoramic radiography is one of the commonly used diagnostic tools for evaluating the relationship of these two structures. OBJECTIVES: To evaluate the accuracy of panoramic radiographic findings in predicting direct contact between mandibular canal and impacted third molars on 3D digital images, and to define panoramic criterion in predicting direct contact between the two structures. METHODS: Two observers examined panoramic radiographs of 178 patients (256 impacted mandibular third molars). Panoramic findings of interruption of mandibular canal wall, isolated or with darkening of third molar root, diversion of mandibular canal and narrowing of third molar root were evaluated for 3D digital radiography. Direct contact between mandibular canal and impacted third molars on 3D digital images was then correlated with panoramic findings. Panoramic criterion was also defined in predicting direct contact between the two structures. RESULTS: Panoramic findings of interruption of mandibular canal wall, isolated or with darkening of third molar root were statistically significantly correlated with direct contact between mandibular canal and impacted third molars on 3D digital images (p < 0.005), and were defined as panoramic criteria in predicting direct contact between the two structures. CONCLUSION: Interruption of mandibular canal wall, isolated or with darkening of third molar root observed on panoramic radiographs were effective in predicting direct contact between mandibular canal and impacted third molars on 3D digital images. Panoramic radiography is one of the efficient diagnostic tools for pre-operative assessment of impacted mandibular third molars. PMID- 27398106 TI - Diagnosis and Intralesional Corticotherapy in Oral Ulcers Occurring as the Sole Manifestation of Langerhans Cell Histiocytosis. A Case Report. AB - This article reports a case of oral mucosa lesions as the sole manifestation in Langerhans cell histiocytosis (LCH). This is a very uncommon manifestation of LCH since this disease preferably affects the bones with frequent involvement of the jaws. LCH may also involve other organs, particularly the lungs, liver, lymph nodes, and skin. The highlights of this report are the differential diagnosis, immunohistochemical analysis and, mostly, the therapeutic approach. PMID- 27398107 TI - Reliability and Validity of Electro-Goniometric Range of Motion Measurements in Patients with Hand and Wrist Limitations. AB - STUDY DESIGN: Cross-sectional reliability and validity study. PURPOSE: 1. To determine intrarater, interrater and inter instrument reliabilities and validity of two digital electro goniometry to measure active wrist/finger range of motions (ROMs) in patients with limited motion. 2. To determine intrarater and interrater reliabilities of digital goniometry to measure torques of PIP passive flexion of the index finger in patients with limited motion. METHODS: The study was designed in a randomized block plan on 44 patients (24 women, 20 men) with limited wrist or hand motions. Two experienced raters measured active wrist ROMs, and active and passive index PIP flexion using two digital goniometers. All measures were repeated by one rater 2-5 days after the initial measurements. The reliability measures were analyzed using Intraclass Correlation Coefficients (ICCs) and the construct validity was determined by correlation coefficients analysis between sub measures of scores; patient rated pain and function (PRWE) and quick Disabilities of the Arm, Shoulder and Hand (quick DASH) scores. RESULTS: The intrarater, interrater and inter instrument reliabilities were high in most ROM measures (range 0.64-0.97) for both types of electro-goniometers. The 95% limit of agreements and Bland and Altman plots did not show progressive changes. There was a significant difference in force application between the raters when performing passive ROM measures for PIP index, but the same rater produced consistent force. Most of the NK and J-Tech ROM measures were moderately correlated with the patient rated pain and function scores (range 0.32-0.63). PMID- 27398108 TI - Late Anterior Dislocation Due to Posterior Pelvic Tilt in Total Hip Arthroplasty. AB - BACKGROUND: Excessive pelvic tilt may be one of the factors leading to instability in total hip arthroplasty (THA), even when the acetabular cup is placed properly. To our knowledge, only a few studies have described late anterior dislocation due to posterior pelvic tilt. We present 3 cases with late anterior dislocations possibly due to posterior pelvic tilt. CASES PRESENTATIONS: Case-1: An 84-years-old woman fell and presented with an anterior dislocation 12 years after THA. Her pelvis had tilted to approximately 30 degrees posteriorly in a supine position. After conservative treatment, she presented with 10 recurrent anterior dislocations. She had thoracolumbar kyphosis due to multiple compression fractures. Revision with anterior placement of an elevated liner and a 32-mm head corrected the dislocation, and no further dislocations occurred. Case-2: A 78-years-old woman fell and presented with an anterior dislocation 4 years after THA. Her posterior pelvic tilt had increased 23 degrees due to a lumbar compression fracture. Revision by decreasing the cup anteversion was performed, but recurrent posterior dislocations occurred. Owing to her worsened general condition, further treatment was abandoned. Case-3: A 79-years-old woman twisted her body and presented an anterior dislocation 3-years after THA. After manual reduction and conservative treatment, the dislocation recurred. Her posterior pelvic tilt had increased 16 degrees . CONCLUSION: Although minor trauma triggered the anterior instability in these patients, the underlying pathomechanism existed in the progressive pelvic posterior tilt due to thoracolumbar kyphosis. As longer life expectancy as well as implant survivorship is predicted, attention must be paid to the change of pelvic tilt in elderly patients. PMID- 27398109 TI - Preoperative Determinants of Patient-reported Pain and Physical Function Levels Following Total Knee Arthroplasty: A Systematic Review. AB - BACKGROUND: A sound knowledge of the determinants of total knee arthroplasty (TKA) outcomes could help in patient selection, preparation and education. We aimed to assess the current status of the literature evaluating preoperative determinants of early and medium term patient-reported pain and disability following TKA. METHOD: A search in Medline, Pubmed, Embase and CINAHL until October 2014 was undertaken. Selection criteria included: 1- participants undergoing primary unilateral TKA with a follow-up from 6 months to 2 years, 2- validated disease-specific patient-reported outcome measures assessing pain and/or function used as outcome measure and 3- identification of preoperative determinants obtained via multivariate analyses. Risk of bias was assessed using a modified version of the Methodology checklist for prognostic studies. RESULTS: Thirty-three prognostic explanatory studies were included. Mean total score of the methodological quality was 80.7+/-12.2 %. Sociodemographic and psychosocial determinants included greater socioeconomic deprivation (both studies), greater levels of depression and/or anxiety (7 out of 10 studies) and greater preoperative pain catastrophizing (all 3 studies). Significant clinical determinants included worse pre-operative knee related pain or disability (20 out of 22 studies), presence or greater levels of comorbidity (12 out of 23 studies), back pain (4 out of 5 studies) and lower general health (all 11 studies). CONCLUSION: Several significant determinants of short to medium-term pain and functional outcomes following TKA have been summarized by studies with moderate to-high methodological quality. No conclusions can be reached regarding the strength of the associations between significant determinants and TKA results because of heterogeneity of study methodologies and results. Further high-quality research is required. PMID- 27398110 TI - Addressing HIV/AIDS among Aboriginal People using a Health Status, Health Determinants and Health Care Framework: A Literature Review and Conceptual Analysis. AB - OBJECTIVES: (1) To describe the Human Immunodeficiency Virus (HIV) infection among Aboriginal populations using a mixed methods approach (i.e. quantitative and qualitative methods); (2) to examine the individual-level and community-level relationships between HIV/AIDS, health determinants, and health care (e.g. diagnosis, access to treatment and health services planning); and (3) to explore innovative solutions to address HIV/AIDS among Aboriginal populations based upon research and infrastructure (e.g. partnerships, data sources and management, health indicators and culture) and policy (i.e. self-determination of Aboriginal Peoples). METHODS: Literature review and conceptual analysis using a health status, health determinants and health care framework. RESULTS: In comparison to non-Aboriginal persons, HIV infection is higher among Aboriginal persons, is more directly attributable to unique risk factors and socio-demographic characteristics, and yields more adverse health outcomes. Culture, poverty and self-determination are determinants of health for Aboriginal populations. Aboriginal people have inadequate primary care and, in particular, specialist care. It is necessary to include traditional Aboriginal approaches and culture when addressing Aboriginal health while understanding competing paradigms between modern medicine and Aboriginal traditions. CONCLUSION: There is a need for self determination of Aboriginal Peoples in order to improve the health of Aboriginal communities and those living with HIV/AIDS. Research and policy affecting Aboriginal people should be of the highest quality and based upon Aboriginal community relevance and involvement. PMID- 27398111 TI - Getting the Canadian HIV epidemic to zero: Valuing indigenous cultures through holistic research. AB - This paper was orally presented at the Canadian Aboriginal AIDS Network, Wise Practices IV - Community-Based Research Gathering on September 25, 2013 in Saskatoon, Saskatchewan, Canada as the LaVerne Monette Memorial Lecture. The objectives of this paper are: (1) to describe the HIV epidemic among Aboriginal people living in Canada; and (2) to examine the value of incorporating indigenous cultures into research within the context of holistic research perspectives. The methodology used to address the objectives was an integrative review (i.e., structured review) of the literature. The major results of this review revealed that while Aboriginal people make up 3.8% of the Canadian population, they represent 12.2% of all new HIV infections in 2011. In 2011, a full 81% of newly diagnosed HIV cases in the Province of Saskatchewan were of Aboriginal ethnicity. Although there are diverse approaches to conducting research involving Aboriginal populations (e.g., critical social paradigm, indigenous research paradigm, and critical indigenous pedagogy vis-a-vis critical, indigenous qualitative research), each has its unique challenges. This paper concludes that Aboriginal people are overrepresented in the Canadian HIV epidemic and that valuing indigenous cultures through holistic research perspectives has the potential to get the Canadian HIV epidemic to zero. PMID- 27398112 TI - Bisphosphonate-induced bilateral acute renal cortical necrosis. AB - Renal cortical necrosis (RCN), a rare cause of renal failure in which there is death of the renal cortex but sparing of the medulla, is a catastrophic entity with high mortality. Its incidence and severity are higher in developing countries, mostly due to pregnancy-related complications. This paper presents the case of a 65-year-old woman who had bilateral renal cortical necrosis caused by bisphosphonate medication that was diagnosed by CT scan during the acute initial phase of the disease. PMID- 27398113 TI - Prospective diagnosis of marginal ulceration following Roux-en-Y gastric bypass with computed tomography. AB - Marginal ulcers are reported to be the most common complication following Roux-en Y gastric bypass surgery. Despite their frequency, they are rarely diagnosed prospectively with cross-sectional imaging. We present four cases in which the diagnosis of marginal ulceration was made prospectively with CT and confirmed with endoscopy. PMID- 27398114 TI - Osseous femoral avulsion of the anterior cruciate ligament origin in an adult. AB - Injuries of the anterior cruciate ligament are commonly encountered in clinical practice, and occur in a wide variety of settings, from sports-related injuries to polytrauma. Tears of the anterior cruciate ligament supersede osseous avulsion in the adult demographic; however, in the pediatric population, osseous avulsion reflects the most frequent injury. When osseous avulsion of the anterior cruciate ligament occurs in children or adults, the injury typically occurs at the level of the tibial eminence. Conversely, osseous avulsion injuries from the femur are rare, with all cases reported in the literature occurring in the skeletally immature. We report a case of a 47-year-old woman who suffered an osseous avulsion of her anterior cruciate ligament from her lateral femoral condyle. To our knowledge, this reflects the first reported case of femoral osseous avulsion of the anterior cruciate ligament origin in an adult. PMID- 27398115 TI - Megalourethra as a rare cause for erectile dysfunction. AB - MRI findings of megalourethra have not previously been reported. We present a case of an adult presenting with lifelong erectile dysfunction secondary to poor development of the corpus spongiosum and corpora cavernosa. The pathogenesis, typical presentation, and treatment of megalourethra, as well as the use of modern imaging techniques to aid in the diagnosis and treatment of this disease are discussed. PMID- 27398116 TI - Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation. AB - A 20-month-old female presented with respiratory distress and a right adrenal mass extending into the inferior vena cava and right atrium. The mass was initially thought to be neuroblastoma. Pathology later revealed adrenocortical carcinoma. Inferior vena cava extension is far more common in adrenocortical carcinoma than neuroblastoma, and its presence should prompt clinical and laboratory evaluation for an adrenocortical tumor. The genetic findings in TP53 associated with this disease are discussed. PMID- 27398117 TI - Acute exertional medial compartment syndrome of the foot in a teenager. AB - Acute compartment syndrome is an emergent condition characterized by increased pressure in a noncompliant fascial compartment, resulting in ischemia of the muscles and nerves. It is most commonly caused by a traumatic etiology but rarely can be caused by an atraumatic etiology, resulting in a confusing clinical scenario. We present a case of a 15-year-old sedentary teenager diagnosed with acute exertional medial compartment syndrome of the foot, initially diagnosed with MRI, following two days of rugby practice. PMID- 27398118 TI - Recurrent pendunculated osteochondroma of the tibia. AB - Osteochondromas have been widely reported in the literature. Surgical management can be a successful primary treatment option, but tumors can occur again in the presence of open epiphyseal growth plates. This case reports a recurrent pedunculated osteochondroma in a 15-year-old female. PMID- 27398119 TI - Tablets or scalpel: Pituitary hyperplasia due to primary hypothyroidism. AB - We describe a patient with pituitary hyperplasia due to primary hypothyroidism. Pituitary hyperplasia and pituitary masses cannot be reliably differentiated on imaging alone, despite significant improvement in imaging quality in recent years. PMID- 27398120 TI - Intermittent enhancement in chronic nodular calcified neurocysticercosis. AB - Neurocysticercosis (NCC) is the most common cause of new onset seizures and epilepsy in the developing and tropical world. There has been a marked increase in domestic cases of diseases traditionally associated with developing countries, and now NCC should be high on a radiologist's differential diagnosis list for a patient with seizures. Radiologic findings of NCC correlate with the parasite's life cycle within the host. The calcified granulomas signify the final stage (nodular calcified) as nonenhancing punctate calcifications on imaging and are traditionally known to remain without enhancement. Here we describe a unique case of intermittent enhancement of a cortical calcified nodule secondary to NCC that was followed for over 10 years. Radiologists must challenge the traditionally accepted progression of imaging findings and accept that calcified nodules of chronic NCC may intermittently enhance. PMID- 27398121 TI - Infant with nasolacrimal sinonasal myxoma: Diffusion MRI features. AB - We report the imaging features of a rare sinonasal myxoma situated over the right nasolacrimal duct in a 5-month-old male. We emphasize the importance of including sinonasal myxomas in the list of differential diagnostic possibilities when encountering a nasolacrimal gland mass in an infant, and describe the CT and MRI characteristics of this rare entity. PMID- 27398122 TI - Geniculate artery embolization for recurrent postarthroplasty hemarthrosis of the knee. AB - Hemarthrosis after total knee arthroplasty is an uncommon condition. We present a unique case of recurrent hemarthrosis in a 93-year-old woman two years after an uneventful total knee arthroplasty and describe how we successfully treated her with selective angiographic embolization of the geniculate arteries. PMID- 27398123 TI - Hemodynamic alterations measured with phase-contrast MRI in a giant cerebral aneurysm treated with a flow-diverting stent. AB - Many risk factors have been proposed in the development of the cerebral aneurysms. Hemodynamics including blood velocity, volume flow rate (VFR), and intravascular pressure are thought to be prognostic indicators of aneurysm development. We hypothesize that treatment of cerebral aneurysm using a flow diverting stent will bring these hemodynamic parameters closer to those observed on the contralateral side. In the current study, a patient with a giant cerebral aneurysm was studied pre- and postoperatively using phase contrast MRI (PC-MRI) to measure the hemodynamic changes resulting from the deployment of a flow diverting stent. PC-MRI was used to calculate intravascular pressure, which was compared to more invasive endovascular catheter-derived measurements. After stent placement, the measured VFRs in vessels of the treated hemisphere approached those measured on the contralateral side, and flow symmetry changed from a laterality index of -0.153 to 0.116 in the middle cerebral artery. Pressure estimates derived from the PC-MRI velocity data had an average difference of 6.1% as compared to invasive catheter transducer measurements. PC-MRI can measure the hemodynamic parameters with the same accuracy as invasive methods pre- and postoperatively. PMID- 27398124 TI - Gorham-Stout disease presenting with dyspnea and bone pain in a 9-year-old girl. AB - Gorham-Stout (GS) disease is a rare bone disorder of unknown etiology that is characterized by local proliferation of small vascular or lymphatic channels, resulting in progressive osteolysis and bone resorption. The diagnosis of GS disease is one of exclusion, with radiography and histopathology playing key roles. We describe a 9-year-old girl who presented to us with dyspnea and bone pain. She was found to have a cystic mass of the upper extremity, multiple cystic bone lesions, multiple fractures of different ages, and pleural effusions. We review the radiologic images that helped establish the diagnosis of GS disease. PMID- 27398125 TI - FDG-PET-positive lower-extremity sebaceous-gland carcinoma in a patient with Muir Torre syndrome. AB - Sebaceous-gland carcinoma can occur alone or as one of the defining features of the Muir-Torre syndrome. Cases occurring below the head and neck are extremely rare. Here we describe the case of a 70-year-old male with Muir-Torre syndrome who had a recurrent sebaceous-gland carcinoma in the left lower extremity that demonstrated (18)F-FDG avidity. An (18)F-FDG-avid lower-extremity sebaceous-gland carcinoma has not been previously reported. PMID- 27398126 TI - Benign granular-cell tumor of the breast: Case report and literature review. AB - Granular-cell tumor is an uncommon cause of breast mass in premenopausal women that presents as a painless chronic lump. It mimics infiltrating carcinoma clinically and radiologically. Granular-cell tumor is usually benign, and the treatment is wide local excision. Definitive pre-operative diagnosis helps to avoid unnecessary mastectomy. We present clinical, mamographic, and sonographic characteristics of a benign granular-cell tumor of the breast in a 57-year-old woman. PMID- 27398127 TI - Extraosseus Ewing sarcoma: An uncommon periclavicular location. AB - A rapidly enlarging right sternoclavicular mass in a young male was labeled as a nonspecific mass. MRI played a crucial role in characterizing the lesion, helping to define the possible mesenchymal origin and the relative involvement of the surrounding structures. We also discuss the differential diagnosis of an extraosseus Ewing sarcoma (ES), with its imaging findings. PMID- 27398128 TI - Usefulness and role of magnetic resonance imaging in a case of complete androgen insensitivity syndrome. AB - Complete androgen insensitivity syndrome (CAIS) is an X-linked, recessive disorder caused by mutations of the androgen receptor (AR), in which genetic males (46,XY) show female external genitalia. Individuals with CAIS have mostly normal external genitalia, lack of Mullerian structures (Fallopian tubes, uterus, proximal portion of the vagina) and undescended testes (intra-abdominal, inguinal, or labial). Management and diagnosis of CAIS should be undertaken by a multidisciplinary team of experts in sexual development disorders. Gonadectomy represents a standard therapeutic choice to prevent testicular malignancy in the prepubertal period, with subsequent hormonal replacement therapy, or in late adolescence, after completion of pubertal development. Imaging examinations play a pivotal role in the diagnosis, assessment, and detection of the gonads before surgical treatments. Magnetic resonance imaging (MRI) is the gold standard to diagnose and locate the gonads, and to plan laparoscopic gonadectomy and gonadic surveillance, in particular in the increasingly large number of patients who decide to delay or ultimately not to undergo gonadectomy. We present a case of a 14-year-old female with primary amenorrhea. PMID- 27398129 TI - Radiologic presentation of lipoid proteinosis with symmetrical medial temporal lobe calcifications. AB - Lipoid proteinosis is a rare, autosomal-recessive, genetic disorder characterized by multisystem involvement due to intracellular deposition of amorphous hyaline material. The disease is due to a mutation in the extracellular matrix of the protein 1 gene. The skin, mucosa, and central nervous system are commonly affected. Hallmark findings in the brain are calcifications, mostly occurring in the amygdala, hippocampus, parahippocampal gyrus, and striatum. Moniliform blepharosis, a dermatologic condition that is present in 50% of patients, is a pathognomonic finding. In the other 50% of patients, imaging assists in the diagnosis. We present a case of lipoid proteinosis with its characteristic features. PMID- 27398130 TI - Filariasis presenting as acute abdominal pain: The role of imaging and image guided intervention in diagnosis. AB - Filariasis is an endemic infection seen in tropical and subtropical regions of the world that presents with lymphatic dysfunction in the form of lymphocoele, hydrocoele, chyluria, or groin lymphadenovarix. We report a case of filariasis with the unusual presentation of acute abdominal pain in which radiographic imaging modalities played a crucial role in diagnosis. PMID- 27398131 TI - Lingular pneumonia obscured by implanted cardioverter-defibrillator: Lateral thinking. AB - A 56-year-old female with an implanted cardioverter-defibrillator was admitted with a short history suggestive of a diagnosis of pneumonia. An AP radiograph did not identify an area of consolidation. A subsequent lateral radiograph highlighted an extensive left-lingular-lobe consolidation that had been obscured by the cardiac device. This case highlights the fact that large devices can obscure significant pathology, and that lateral or cross-sectional imaging may be helpful in reaching a diagnosis. PMID- 27398132 TI - Dry Matter Losses and Greenhouse Gas Emissions From Outside Storage of Short Rotation Coppice Willow Chip. AB - This study examined the dry matter losses and the greenhouse gas (GHG) concentrations within two short rotation coppice (SRC) willow wood chip storage heaps. One heap was built on a grassland area (East Midlands) and the other (Rothamsted) on a concrete hard standing. A series of 1- and 3-m probes were embedded in the heaps in order to retrieve gas samples for analysis, and pre weighed net bags were positioned in the core of the heap to detect dry matter losses. The bagged samples showed dry matter losses of 18 and 19 % in the East Midlands and Rothamsted heaps after 210 and 97 days storage, respectively. The Rothamsted heap showed a whole-heap dry matter loss of 21 %. During this time, the wood chips dried from 54 to 39 % moisture content in the East Midlands heap and 50 to 43 % at Rothamsted. The results from analysing the whole Rothamsted heap indicated an overall loss of 1.5 GJ per tonne stored, although measurements from bagged samples in the core suggested that the chips dried sufficiently to have a minimal energy loss from storage. The process of mixing the heap, however, led to incorporation of wet outer layers and hence the average moisture content was higher in an average sample of chip. After establishment of the heaps, the temperature rose rapidly and this correlated with a peak in carbon dioxide (CO2) concentration within the heap. A peak in methane (CH4) concentration was also detected in both heaps, though more noticeably in the East Midlands heap after around 55 days. In both instances, the peak CH4 concentration occurred as CO2 concentrations dropped, suggesting that after an active period of aerobic decomposition in the first 2 months of storage, the conditions in the heap became anaerobic. The results from this study suggest that outside wood chip storage is not an efficient method of storing biomass, though this may be location-specific as there are some studies showing lower dry matter losses. It is necessary to explore other methods of harvesting SRC to minimise losses and optimise land use efficiency. Further research is required to detect whether there are fugitive emissions of CH4 from wood chip heaps, as this will compromise the net GHG savings from utilising the biomass stored in this way. PMID- 27398134 TI - Inflammatory bowel disease related innate immunity and adaptive immunity. AB - Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn's disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD. PMID- 27398135 TI - Extracellular matrix metalloproteinase inducer (CD147/BSG/EMMPRIN)-induced radioresistance in cervical cancer by regulating the percentage of the cells in the G2/m phase of the cell cycle and the repair of DNA Double-strand Breaks (DSBs). AB - Our preliminary study found that CD147 is related to radioresistance and maybe an adverse prognostic factor in cervical cancer. To date, the mechanisms underlying CD147-induced radioresistance in cervical cancer remain unclear. In the present study, we investigated the mechanisms by which CD147 affects radiosensitivity in cervical cancer both in vitro and in vivo. In this study, the clonogenic assay showed that radiosensitivity was significantly higher in the experimental group (the CD147-negative cell lines) than in the control group (the CD147-positive cell lines). After radiotherapy, the residual tumour volume was significantly lower in the experimental group. FCM analysis showed the cells percentage in the G2/M phase of the cell cycle were significantly higher in the CD147-negative group than in the control group. However, there was no significant difference in terms of apoptosis. The expression of gamma-H2A histone family, member X (gammaH2AX) was dramatically elevated in the CD147-negative cell lines after irradiation, but the expression of ataxia-telangiectasia mutated (ATM) was not different between the two groups. WB analysis did not show any other proteins relating to the expression of CD147. In conclusion, it is likely that CD147 regulates radioresistance by regulating the percentage of the cells in the G2/M phase of the cell cycle and the repair of DNA double-strand breaks (DSBs). Inhibition of CD147 expression enhances the radiosensitivity of cervical cancer cell lines and promotes post-radiotherapy xenograft tumour regression in nude mice. Therefore, CD147 may be used in individualized therapy against cervical cancer and is worth further exploration. PMID- 27398133 TI - Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials. AB - Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative muscle disorder caused by the absence of dystrophin. There is no curative therapy, although innovative therapeutic approaches have been aggressively investigated over recent years. Currently, the international clinical trial registry platform for this disease has been constructed and clinical trials for innovative therapeutic approaches are underway. Among these, exon skipping and read-through of nonsense mutations are in the most advanced stages, with exon skipping theoretically applicable to a larger number of patients. To date, exon skipping that targets exons 51, 44, 45, and 53 is being globally investigated including in USA, EU, and Japan. The latest announcement from Japan was made, demonstrating successful dystrophin production in muscles of patients with DMD after treating with exon 53 skipping antisense oligonucleotides (ASOs). However, the innovative therapeutic approaches have demonstrated limited efficacy. To address this issue in exon skipping, studies to unveil the mechanism underlying gymnotic delivery of ASO uptake in living cells have been conducted in an effort to improve in vivo delivery. Further, establishing the infrastructures to integrate multi institutional clinical trials are needed to facilitate the development of successful therapies for DMD, which ultimately is applicable to other myopathies and neurodegenerative diseases, including spinal muscular atrophy and motor neuron diseases. PMID- 27398136 TI - miR-223/FBW7 axis regulates doxorubicin sensitivity through epithelial mesenchymal transition in non-small cell lung cancer. AB - Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths in the world. F-box/WD repeat-containing protein 7 (FBW7) plays important roles in human cancers, such as gastric cancer, breast cancer, and hepatocellular carcinoma. In this study, we found that high levels of FBW7 expression were associated with increased doxorubicin sensitivity in NSCLC cells. Down-regulation of FBW7 reduced the chemosensitivity in tumor cells. Twist is a critical transcription factor in epithelial-mesenchymal transition (EMT), and NSCLC cells with silenced Twist showed increased doxorubicin sensitivity. Treatment of cells with doxorubicin or hypoxia was shown to trigger EMT as evidenced by decreased E cadherin and increased Vimentin. In contrast, ectopic expression of FBW7 prevented doxorubicin-or hypoxia-induced EMT. In addition, FBW7 was identified as a functional target of miR-223 in NSCLC cells. These findings define a critical role of miR-223/FBW7 pathway in regulating EMT and chemosensitivity in NSCLC cells. PMID- 27398137 TI - Effect of 5-HT7 receptor agonist, LP-211, on micturition following spinal cord injury in male rats. AB - BACKGROUND AND PURPOSE: Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role in regulation of micturition reflex. The aim of this study was to evaluate effect of a 5-HT7 receptor agonist, LP-211 (N-(4 cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide) on micturition reflex in acute spinal cord-injured (SCI) rats during infusion of vehicle into the bladder. METHODS: SCI was induced by compressing T10 segment using an aneurysm clip, extradurally in male rats. Following two weeks, LP-211 doses (0.003-0.3 mg/kg) were administered cumulatively (intraperitoneally, i.p.) with 20 min interval. The 5-HT7 antagonist, SB-269970 ((R)-3-[2-[2-(4-Methylpiperidin-1-yl) ethyl] pyrrolidine-1-sulfonyl] phenol hydrochloride), was administered after achievement of LP-211 dose-response. A cystometric study was performed 2 weeks after spinal crushing in all the animals. Cystometric variables consisting of micturition volume (voided volume), residual volume (volume remaining in the bladder after voiding), and bladder capacity (micturition volume plus residual volume). Voiding efficiency was calculated as the percent of micturition volume to bladder capacity. FINDINGS: Intact and sham-operated rats showed few significant changes in micturition reflex. SCI rats responded to LP-211 (0.003 0.3, mg/kg, i.v.) with dose-dependent increases in bladder capacity, and residual volume. In this treatment group, LP-211 induced significant dose-dependent increases in micturition volume, resulting in significant increases in voiding efficiency (P<0.001) compared to intact and sham-operated rats, SB-269970 (0.1 mg/kg, i.v.) completely reversed the LP-211-induced changes on micturition volume and voiding efficiency was decreased significantly. CONCLUSION: The 5-HT7 receptors activation by LP-211 facilitated the micturition reflex. Furthermore, 5 HT7 receptors do seem to play an important role in physiological regulation of micturition, and as a result, may represent a new strategy to improve voiding efficiency after SCI in patients in the future perspective. PMID- 27398138 TI - JNK/PI3K/Akt signaling pathway is involved in myocardial ischemia/reperfusion injury in diabetic rats: effects of salvianolic acid A intervention. AB - Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3 kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A). The inhibitor of JNK (SP600125) and Sal A were used in type 2 diabetic (T2D) rats, outcome measures included heart hemodynamic data, myocardial infarct size, the release of lactate dehydrogenase (LDH), SERCA2a activity, cardiomyocyte apotosis, expression levels of Bcl-2, Bax and cleaved caspase-3, and the phosphorylation status of Akt and JNK. The p-Akt levels were increased after myocardial I/R in non-diabetic rats, while there was no change in diabetic rats. Pretreatment with the SP600125 and Sal A decreased the p-JNK levels and increased the p-Akt levels in diabetic rats with I/R, and heart hemodynamic data improved, infarct size and LDH release decreased, SERCA2a activity increased, Bax and cleaved caspase-3 expression levels decreased, and the expression of Bcl-2 and the Bcl-2/Bax ratio increased. Our results suggest that the JNK/PI3K/Akt signaling pathway is involved in myocardial I/R injury in diabetic rats and Sal A exerts an anti-apoptotic effect and improves cardiac function following I/R injury through the JNK/PI3K/Akt signaling pathway in this model. PMID- 27398139 TI - Periprostatic implantation of neural differentiated mesenchymal stem cells restores cavernous nerve injury-mediated erectile dysfunction. AB - Mesenchymal stem cells (MSCs) have been utilized to restore erectile function in animal models of cavernous nerve injury (CNI). However, transplantation of primary MSCs may lead to unpredictable therapeutic outcomes. In this study, we investigated the efficiency of neural differentiated MSCs (d-MSCs) on the restoration of erectile function in CNI rats. Rat bone marrow MSCs (r-BM-MSCs) were treated with all-trans retinoic acid to induce neural differentiation. Rats were divided into five groups: a sham operation group; a bilateral CNI group that received an intracavernous injection of r-BM-MSCs (IC group); and three groups that received periprostatic implantation of either r-BM-MSCs (IP group), d-MSCs (IP-d group), or PBS (PBS group). The data revealed that IP injection of d-MSCs ameliorated erectile function in a similar manner to an IC injection of MSCs and enhanced erectile function compared to an IP injection of MSCs. An in vivo time course of d-MSCs survival revealed that PKH26-labled d-MSCs were detectable either within or surrounding the cavernous nerve tissue. In addition, the expression of caspase-3 significantly increased in the PBS group and decreased after treatment with MSCs, especially in the IC and IP-d groups. Furthermore, the expression levels of neurotrophic factors increased significantly in d-MSCs. This study demonstrated that periprostatic implantation of d-MSCs effectively restored erectile function in CNI rats. The mechanism might be ascribed to decreases in the frequency of apoptotic cells, as well as paracrine signaling by factors derived from d-MSCs. PMID- 27398141 TI - Identification a novel tumor-suppressive hsa-miR-599 regulates cells proliferation, migration and invasion by targeting oncogenic MYC in hepatocellular carcinoma. AB - Increasing evidences have demonstrated that microRNAs (miRNAs) act an essential role in regulating tumor progression and metastasis. Previous miRNAs microarray data showed that hsa-miR-599 is lower expressed in hepatocellular carcinoma (HCC); however, the function and molecular mechanism of hsa-miR-599 on HCC has not been well illustrated. Here, we first analyzed the expression level of hsa miR-599 in HCC tissues and cell lines by real-time reverse-transcription PCR (qRT PCR). Interestingly, we found that hsa-miR-599 was significantly down-regulated in the examined HCC tissues and cell lines. Then cells proliferation, migration and invasion were assessed by MTT, wound-healing and trans-well assay respectively. The results showed that over-expression of hsa-miR-599 resulted in inhibited HCC cells proliferation, migration and invasion in vitro. In addition, dual-luciferase reporter assay, qRT-PCR and Western blot analyzes were used to confirm MYC (v-myc avian myelocytomatosis viral oncogene homolog) as a target gene of hsa-miR-599. MYC expression was up-regulated in HCC tissues and cell lines, and restoration of hsa-miR-599 could remarkably decreased the mRNA and protein levels of MYC. Moreover, over-expression of MYC partly reversed hsa-miR 599-mediated inhibition of HCC cells proliferation, migration and invasion in vitro. Taken together, our data demonstrate that hsa-miR-599 acts as a tumor suppressor and inhibits HCC cells proliferation, migration and invasion by partly targeting oncogenic MYC, which hints that hsa-miR-599 can be a diagnostic and therapeutic biomarker in HCC. PMID- 27398140 TI - Growing a whole porcine liver organ ex situ for six hours without red blood cells or hemoglobin. AB - Liver transplantation is an effective approach to end-stage liver disease. Shortage of donor liver and increased waiting time for liver transplantation necessitate the development of an organ culture system by which livers can be cultured and maintained ex situ for a prolonged period of time. The aim of this work is to test whether cell culture condition in vitro could be used to culture whole livers ex situ without the use of erythrocytes. Twelve castrated male land race/farm young porcine livers were exposed to 30 min warm ischemia and 30 min cold perfusion. Livers were isolated and connected to an Ex situ liver culture system using a standard culture medium RPMI1640 supplied with 10% of fetal bovine serum and sufficient dissolved oxygen under a normothermic condition for 6 hours. Metabolic biomarkers, bile and urea production, hepatic cell viability and histology analysis of biopsies were examined and newly proliferated hepatic cells labeled by BrdU were analyzed after 6 hours ex situ culture. The results from biochemical assays and histology analysis indicate that livers after the organ culture still maintain the full function. CONCLUSIONS: Our data demonstrate that the liver culture system established in this work can be used to culture whole livers ex situ in the absence of erythrocytes. PMID- 27398142 TI - Ultrasound-induced microbubble destruction promotes targeted delivery of adipose derived stem cells to improve hind-limb ischemia of diabetic mice. AB - This study aimed to investigate whether ultrasound-induced microbubble destruction was able to promote targeted delivery of adipose-derived stem cells (ASCs) to improve hind-limb ischemia of diabetic mice. Ischemia was induced in the lower limb of db/db mice which were then randomly divided into 5 groups: PBS group, Sham group, ultrasound + microbubble group (US+MB), US+MB+ASCs group and ASCs group. Contrast-enhanced ultrasound perfusion imaging showed the ratio of blood flow in ischemic hind-limb to that in contralateral limb increased over time in five groups. A significant enhancement in US+MB+ASCs group was observed compared with US+MB group (P<0.01). Immunofluorescence microscopy of hind-limb muscle showed the microvessel density (microvessels/skeletal muscle fibers) and arteriolar density in US+MB+ASCs group were higher than in US+MB group, and significantly higher than in other control groups (P<0.01). Masson staining indicated the degree of muscle fibrosis in US+MB+ASCs group was lower than in US+MB. 3 and 7 days after therapy, ELISA and RT-PCR showed the expression of VEGF, P-selectin, ICAM-1 and SDF-1 in US+MB+ASCs group was higher than in US+MB group, and dramatically increased as compared to other groups (P<0.01). 3 and 7 days after therapy, Western blot assay showed the protein expression of P-P13K, P AKT, VEGF, P-selectin, ICAM-1 and SDF-1 in US+MB+ASCs group was higher than US+MB group (P<0.01). The bioeffects of ultrasound-induced microbubble cavitation is able to up-regulate the expression of pro-inflammatory cytokines, which may improve the targeted delivery, adhesion and paracrine of ASCs, attenuating the hind-limb ischemia in diabetic mice. PMID- 27398143 TI - Isoflurane reduces oxygen-glucose deprivation-induced oxidative, inflammatory, and apoptotic responses in H9c2 cardiomyocytes. AB - Isoflurane (ISO) protects the heart from hypoxia-reperfusion injury. However, the molecular mechanisms of ISO in oxygen-glucose deprivation (OGD)-induced H9c2 cardiomyocyte injury is yet to be understood. Using H9c2 cells cultured in vitro, we examined the cytotoxicity of different doses of ISO (0.7%, 1.4%, and 2.1%) to H9c2 cells and found that 2.1% ISO had significant toxicity to the cell. Thus, 1.4% ISO was selected for the subsequent experiments. ISO notably ameliorated cell viability loss, lactate dehydrogenase release, and creatine kinase activity of H9c2 cells that were treated with OGD. ISO suppressed OGD-induced pro inflammatory tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8 production, and nuclear factor (NF)-kappaB activation in H9c2 cells. ISO reduced the reactive oxygen species and malondialdehyde generation, but it enhanced the superoxide dismutase activity in OGD-stimulated H9c2 cells. In addition, diminished OGD-induced cell apoptosis and preserved mitochondrial membrane potential were observed in ISO-treated H9c2 cells. ISO markedly up-regulated the anti-apoptotic Bcl-2 expression but inhibited the pro-apoptotic expressions of Bax, procaspase-3, cleaved caspase-3, and caspase-3 activity. Mechanistically, the cardioprotective effects of ISO on OGD-induced H9c2 cell injury were mediated by the Akt signaling pathway. These findings suggest that ISO alleviates OGD induced H9c2 cell injury and may therefore be used to prevent and treat ischemic heart diseases. PMID- 27398144 TI - miR-449a inhibits proliferation and invasion by regulating ADAM10 in hepatocellular carcinoma. AB - MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a crucial role in tumor procession. It has been demonstrated that miR-449a expression was downregulated and served as tumor suppressor in many types of tumor. However, the biological function and molecular mechanism of miR-449a in hepatocellular carcinoma (HCC) still remains largely unknown. Therefore, the aims of this study were to investigate biological role and molecular mechanism of miR-449a in HCC by a serial of molecular experiments. Here, we demonstrated that miR-449a expression was downregulated in HCC tissues and cell lines compared with the adjacent nontumor tissues and normal hepatic cell line. Ectopic expression of miR-449a suppressed HCC cell proliferation, colony formation, migration and invasion. Moreover, A Disintegrin And Metalloproteinases 10 (ADAM10) was identified as a direct target gene of miR-449a in HCC cell. ADAM10 expression was upregulated in HCC tissues and cell lines, and was negatively correlated with the expression level of miR-449a in HCC tissues. Interesting, overexpression of ADAM10 attenuated the inhibition effect of miR-449a-mediated HCC cell proliferation, colony formation, migration and invasion. These results suggested that miR-449a might function as a tumor suppressor miRNA, at least in part, through regulating ADAM10 expression in HCC. PMID- 27398145 TI - MicroRNA-154 inhibits growth and invasion of breast cancer cells through targeting E2F5. AB - Accumulating evidence suggested that microRNA-154 (miR-154) might play important roles in the development of various cancer types. However, the role of miR-154 in breast cancer progression remains largely unknown. Here, miR-154 expression level was measured via quantitative real-time RT-PCR (qRT-PCR) in 36 pairs of human breast cancer tissues and adjacent normal breast tissues and in a panel of human breast cancer cell lines. Cell proliferation, cycle, migration, and invasion were assessed by CCK8 assay, flow cytometer assay, wound healing assay and transwell invasion assay, respectively. Luciferase reporter assay and Western blot was used to verify E2F transcription factor 5 protein (E2F5) as a novel target gene of miR 154. Our results showed that miR-154 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-154 in MCF-7 cells significantly inhibited cell proliferation, migration, and invasion, and increased cell arrest at G0/G1 stage in vitro. E2F5 was identified as a target of miR-154, and its expression was inversely correlated with miR-154 expression in clinical breast cancer tissues. In addition, downregulation of E2F5 in MCF7 cells had similar effect on cell proliferation, cycle, migration and invasion by miR 154 induced. These findings indicate that miR-154 acts as a tumor suppressor by targeting E2F5, suggesting miR-154 as a potential therapeutic target for the treatment of breast cancer. PMID- 27398146 TI - Neuroprotective effect of endogenous cannabinoids on ischemic brain injury induced by the excess microglia-mediated inflammation. AB - Increasing evidence has demonstrated the role of endogenous cannabinoids system (ECS) on protecting brain injury caused by ischemia (IMI). Papers reported that microglia-mediated inflammation has become one of the most pivotal mechanisms for IMI. This study was aimed to investigate the potential roles of ECS on neuron protection under microglia-mediated inflammation. Inflammatory cytokines level both in vitro (BV-2 cells) and in vivo (brain tissue from constructed IMI model and brain-isolated microglia) was detected. ECS levels were detected, and its effects on inflammations was also analyzed. Influence of microglia-mediated inflammation on neuron injury was analyzed. Moreover, the effects of ECS on protecting neuron injury were also analyzed. Our results showed that the levels of inflammatory cytokines including TNFalpha and IL-1beta were higher while IKBalpha was lower in IMI model brain tissue, brain-isolated microglia and BV-2 cells compared to the control. Inflammation was activated in microglia, as well as the activation of ECS characterized by the increasing level of AEA and 2-AG. Furthermore, the activated microglia-mediated self-inflammation performed harmful influence on neurons via suppressing cell viability and inducing apoptosis. Moreover, ECS functioned as a protector on neuron injury though promoting cell proliferation and suppressing cell apoptosis which were caused by the activated BV-2 cells (LPS induced for 3 h). Our data suggested that ECS may play certain neuroprotective effects on microglia-mediated inflammations-induced IMI through anti-inflammatory function. PMID- 27398147 TI - Resveratrol attenuated estrogen-deficient-induced cardiac dysfunction: role of AMPK, SIRT1, and mitochondrial function. AB - Large epidemiological studies suggest that there are important differences in the incidence and severity of a wide variety of cardiac diseases, between premenopausal and menopausal women. Recently, it has been demonstrated that resveratrol may has similar function as estrogen. However, whether resveratrol replacement could mimic estrogen to protect heart in ovariectomized mice remains completely unknown. Firstly, the present study has used OVX/CAL model to investigate the effect of RSV on ischemic heart. Echocardiography analysis revealed that RSV administration significantly improved cardiac contractile function in estrogen-deficient mice. RSV also significantly reduced CK and LDH release, and heart infarct size in OVX/CAL group. Secondly, mitochondrial functions, including MRC activities, MDA level, and mitochondrial swelling, were evaluated in OVX mice. It was found that supplementation with RSV could restore mitochondrial function dampened by OVX. Thirdly, these protective functions mediated by RSV were mainly attributed to the enhancement of SIRT1/AMPK activity. In summary, the results support a potential role of resveratrol in the protection of cardiac functions under estrogen depletion status. PMID- 27398148 TI - Circulating MiRNA biomarkers serve as a fingerprint for diabetic atherosclerosis. AB - Type 2 diabetes mellitus induced atherosclerosis (DA) is regarded as a major cause of disability and death in diabetic patients. The early prediction of atherosclerosis in patients DM is necessary. Therefore, we aimed to identify special plasma microRNAs that can serve as a novel non-invasive screening signature of DA patients with atherosclerosis and test its specificity and sensitivity in the early diagnosis of DA. In total, we obtained plasma samples from 285 diabetic atherosclerosis patients and matched diabetic retinopathy (DR) patients, diabetic nephropathy (DN) patients, diabetes mellitus without complication (DM) and healthy controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). Three miRNAs were significantly increased in patients with DA compared with other groups after the multiple stages. The areas under the receiver operating characteristic (AUC) curves of the validated three-plasma miRNAs signature in DA comparing with NC were 0.881, 0.709 and 0.842 while the merged was 0.940 while DA comparing with DM was 0.879, 0.663, 0.731 and the merged was 0.928. The three miRNA could also distinguish DA from DN with an AUC of 0.894, 0.782, 0.910 and 0.963 (merged) as well as from DR with an AUC of 0.876, 0.815, 0.850 and 0.925 (merged). In conclusion, these data provide evidence that plasma miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of DA. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of DA from DR, DN, DM patients. PMID- 27398149 TI - Effects of 1,25(OH)2D3 on proliferation and apoptosis of human glomerular mesangial cells. AB - OBJECTIVE: To investigate the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on cell proliferation and apoptosis of human glomerular mesangial cells. METHODS: Human glomerular mesangial cells were cultured for 48 h and randomly divided into four groups, normal control group (N group), proliferation group (EGF group ), vitamin D3 intervention group (VD3 group), proliferation intervention group (EGF+VD3 group ). Flow cytometry was used to detect the cell cycle and apoptosis rate, and Western blot was used to detect the PCNA and Caspases-3 expression. The effect of 1,25(OH)2D3 on human mesangial cell proliferation was detected by CCK 8. RESULTS: Compared with the control group, G1 phase cells in EGF group were significantly reduced, S, G2/M phase cells were increased, and the higher PI and PCNA expression levels were increased; G1 phase cells in VD3 group were increased, S, G2/M phase cells were decreased, and the lower PI and PCNA expression levels were reduced. Compared with EGF group, G1 phase cells in EGF+VD3 group were increased, S, G2/M phase cells were decreased, and the lower PI and PCNA expression levels were significantly reduced. Compared with normal control group, the apoptosis rate in EGF group was significantly lower, and the Caspase-3 expression level was reduced; the apoptosis rate in VD3 group was significantly higher, and Caspase-3 expression was significantly increased. Compared with EGF group, the apoptotic rate of mesangial cells in EGF+VD3 group was significantly increased, and the Caspase-3 expression level was increased, with significant difference. CONCLUSION: 1,25(OH)2D3 inhibited the proliferation of mesangial cells and induced their apoptosis by blocking the cell cycle, inhibiting expression of PCNA, and upregulating Caspase-3 expression. PMID- 27398150 TI - Defects in dermal Vgamma4 gamma delta T cells result in delayed wound healing in diabetic mice. AB - The skin serves as a physical and chemical barrier to provide an initial line of defense against environmental threats; however, this function is impaired in diabetes. Vgamma4 gamma delta T cells in the dermis are an important part of the resident cutaneous immunosurveillance program, but these cells have yet to be explored in the context of diabetes. In this study, we observed that the impaired maintenance of dermal Vgamma4 gamma delta T cells is caused by reduced production of IL-7 in the skin of diabetic mice, which was closely associated with weakened activation of the mTOR pathway in the epidermis of diabetic mice. Weakened CCL20/CCR6 chemokine signaling resulted in the impaired recruitment of dermal Vgamma4 gamma delta T cells following wounding in diabetic mice. Meanwhile, reduced levels of IL-23 and IL-1beta in the dermis around the wounds of diabetic mice resulted in the impaired production of IL-17 by dermal Vgamma4 gamma delta T cells. Therefore, diminished dermal Vgamma4 gamma delta T cells and impaired IL 17 production by these cells were important factors in the markedly reduced IL-17 levels in the skin around the wounds of diabetic mice. Because reduced IL-17 levels at the wound edge have been closely associated with delayed wound closure in diabetic mice, defects in dermal Vgamma4 gamma delta T cells may be an important mechanism underlying delayed wound healing in diabetic mice. PMID- 27398151 TI - Targeting Notch1 inhibits invasion and angiogenesis of human breast cancer cells via inhibition Nuclear Factor-kappaB signaling. AB - Notch-1, a type-1 transmembrane protein, plays critical roles in the pathogenesis and progression of human malignancies, including breast cancer; however, the precise mechanism by which Notch-1 causes tumor cell invasion and angiogenesis remain unclear. Nuclear factor-kappaB (NF-kappaB), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved in the processes of tumor cell invasion and metastasis, we investigated whether targeting Notch-1 could be mechanistically associated with the down-regulation of NF-kappaB, IL-8, VEGF, and MMP-9, resulting in the inhibition of invasion and angiogenesis of breast cancer cells. Our data showed that down-regulation of Notch-1 leads to the inactivation of NF-kappaB activity and inhibits the expression of its target genes, such as IL-8, VEGF and MMP-9. We also found that down-regulation of Notch-1 decreased cell invasion, and vice versa Consistent with these results, we also found that the down-regulation of Notch-1 not only decreased MMP-9 mRNA and its protein expression but also inhibited MMP-9 active form. Moreover, conditioned medium from Notch-1 siRNA transfected breast cancer cells showed reduced levels of IL-8 and VEGF and, in turn, inhibited the tube formation of HUVECs, suggesting that down-regulation of Notch-1 leads to the inhibition of angiogenesis. Furthermore, conditioned medium from Notch-1 cDNA-transfected breast cancer cells showed increased levels of IL-8 and VEGF and, in turn, promoted the tube formation of HUVECs, suggesting that Notch-1 overexpression leads to the promotion of angiogenesis.We therefore concluded that down-regulation of Notch-1 leads to the inactivation NF-kappaB and its target genes (IL-8, MMP-9 and VEGF), resulting in the inhibition of invasion and angiogenesis. PMID- 27398152 TI - Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors. AB - Cell and growth factor-based tissue engineering has shown great potentials for skeletal regeneration. This study tested its feasibility in reconstructing large mandibular defects and compared the efficacy of varied construction materials and sealing methods. Bilateral mandibular critical-size (5-cm(3)) defects were created on six 4-month-old domestic pigs, and grafted with beta-tricalcium phosphate (betaTCP) only (Group-A), betaTCP with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) (Group-B), and betaTCP with BM-MSCs and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres containing bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) (Group-C). The buccal sides of Groups-B/-C were either sealed by fibrin sealant or by a biodegradable PLGA barrier membrane before soft-tissue closure. Computed tomography (CT), microCT and histology analyses were performed 12 weeks postoperatively. In vitro data demonstrated that BM-MSCs, with MSC properties confirmed, remained vital after integration with betaTCP; and PLGA microspheres exhibited an initial burst followed by slow and continuous release of growth factors over a period of 28 days. In vivo data demonstrated that Group-B/-C sites had significantly greater gap obliteration, higher tissue mineral densities and more residual betaTCP granules (p<0.05, Kruskal-Wallis tests). Qualitatively, Group-B/-C defect sites had started remodeling while Group-A sites were mainly forming new bone to bridge the gaps. Furthermore, betaTCP degradation was not mediated by macrophages or osteoclasts, and was significantly slowed down by sealing the defects with barrier membrane. Combined, these data present a promising formulation composed of betaTCP granules, autologous MSCs, controlled release growth factors and biodegradable PLGA barrier membrane for the reconstruction of critical-size mandibular defects. PMID- 27398153 TI - Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells. AB - OBJECTIVE: Biguanides are anti-diabetic drugs that are thought to have anti tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. METHODS: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. RESULTS: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 MUM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. CONCLUSION: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID- 27398154 TI - MiR-143 targets CTGF and exerts tumor-suppressing functions in epithelial ovarian cancer. AB - A series of recent studies suggested that miR-143 might involve in the tumorigenesis and metastasis of various cancer types. However, the biological function and underlying mechanisms of miR-143 in human epithelial ovarian carcinoma (EOC) remain unknown. Therefore, this study aimed to investigate the miR-143 expression and its clinical diagnosis significance in patients suffering EOC and to analyze its role and underlying molecular mechanism in EOC. Our result showed that the expression levels of miR-143 were downregulated in EOC tissues and cell lines, was associated with International Federation of Gynaecology and Obstetrics (FIGO) stage, pathological grade and lymph node metastasis (all P < 0.01) . Overexpression of miR-143 significantly inhibited EOC cell proliferation, migration, and invasion. Furthermore, computational algorithm combined with luciferase reporter assays identified connective tissue growth factor (CTGF) as the direct target of miR-143 in EOC cells. The expression level of CTGF was significantly increased in EOC tissues, was inversely correlated with miR-143 expression in clinical EOC tissues. Knockdown of CTGF mimicked the suppression effect induced by miR-143 overexpression. Restoration of CTGF expression partially reversed the suppression effect induced by miR-143 overexpression. These results suggested that miR-143 inhibited EOC cell proliferation, migration, and invasion, at least in part, via suppressing CTGF expression. PMID- 27398155 TI - MiR-503 inhibits adipogenesis by targeting bone morphogenetic protein receptor 1a. AB - Adipogenesis plays a key role in the regulation of whole-body energy homeostasis and is critically related to obesity. To overcome obesity and its associated disorders, it is necessary to elucidate the molecular mechanisms involved in adipogenesis. An adipogenesis-related miRNA array analysis demonstrated that miR 503 was differentially expressed before and after adipocyte differentiation; however, the exact role of miR-503 in adipocyte differentiation is unclear. Thus, the objective of this study was to further examine miR-503 in adipocyte differentiation. We found significantly decreased expression of miR-503 during adipocyte differentiation process. Using bioinformatic analysis, miR-503 was identified as a potential regulator of Bone Morphogenetic Protein Receptor 1a (BMPR1a). We then validated BMPR1a as the target of miR-503 using a dual luciferase assay, and found decreased miR-503 and increased BMPR1a expression during adipogenesis. Overexpression of miR-503 in preadipocytes repressed expression of BMPR1a and adipogenic-related factors such as CCAAT/enhancer binding protein a (C/EBPalpha), proliferator-activated receptor-gamma (PPARgamma), and adipocyte protein 2 (AP2). In addition, miR-503 overexpression impaired the phosphoinositol-3 kinase (PI3K)/Akt pathway. Inhibition of miR-503 had the opposite effect. Additionally, BMPR1a interference by siRNA attenuated adipocyte differentiation and the accumulation of lipid droplets via downregulating the PI3K/Akt signaling pathway. Our study provides the first evidence of the role miR-503 plays in adipocyte differentiation by regulating BMPR1a via the PI3K/Akt pathway, which may become a novel target for obesity therapy. PMID- 27398157 TI - Flagellin modulates IgE expression in B cells to initiate food allergy in mice. AB - The initiation mechanism of IgE expression has not been fully understood. Flagellin (FGN) is an important microbial factor in the regulation of immune responses in the intestine. This study tests a hypothesis that FGN plays a crucial role in the isotype switching of IgE in B cells and the initiation of food allergy. In this study, the expression of IgE in B cells was analyzed by real time RT-PCR, Western blotting and chromatin immunoprecipitation. A mouse model was developed to assess the role of Toll like receptor-5 in the development of IgE-mediated allergic reaction in the intestinal mucosa. The results showed that exposure to FGN suppressed the expression of Bcl6 in B cells via increasing the levels of histone deacetylase (HDAC) 7; the latter up regulated the levels of methylated H3K9 and H3K27, down regulated RNA polymerase II and STAT3 (signal transducer and activator of transcription 3) at the Bcl6 promoter locus. Exposure to FGN and IL-4 markedly increased the expression of IgE in B cells via activating p300, H3K4, Pol II and STAT6 at the IgE promoter locus. As compared with the sensitized wild mice, the sensitized TLR5-deficient mice showed no detectable OVA-specific IgE in the serum; mast cells in the intestinal mucosa were not activated, no apparent allergic symptoms were evoked after the specific antigen challenge. In conclusion, FGN facilitates the initiation of food allergy in mice by triggering IgE transcription in B cells in a Th2 polarization environment via activating HDAC7 and suppressing Bcl6 expression. PMID- 27398156 TI - Mepenzolate bromide promotes diabetic wound healing by modulating inflammation and oxidative stress. AB - Diabetic wounds are characterized by persistent inflammation and the excessive production of reactive oxygen species, thus resulting in impaired wound healing. Mepenzolate bromide, which was originally used to treat gastrointestinal disorders in clinical settings, has recently been shown to display beneficial effects in chronic obstructive pulmonary disease and pulmonary fibrosis of a mouse model by inhibiting inflammatory responses and reducing oxidative stress. However,the role of mepenzolate bromide in diabetic wound healing is still unclear. In this study, full-thickness excisional skin wounds were created on the backs of db/db mice, and mepenzolate bromide was topically applied to the wound bed. We found that mepenzolate bromide significantly promoted diabetic wound healing by measuring wound closure rate and histomorphometric analyses. Further studies showed that inflammation was inhibited by assessing the number of macrophages and levels of pro-inflammatory cytokines and pro-healing cytokines in the wounds. Furthermore, oxidative stress was reduced by monitoring the levels of MDA and H2O2 and the activities of glutathione peroxidase and catalase in the wounds. These results demonstrated the potential application of mepenzolate bromide for treating diabetic ulcers and other chronic wounds in clinics. PMID- 27398158 TI - Maresin 1 ameliorates iron-deficient anemia in IL-10(-/-) mice with spontaneous colitis by the inhibition of hepcidin expression though the IL-6/STAT3 pathway. AB - BACKGROUND: Approximately 50% of patients with inflammatory bowel disease (IBD) suffer from anemia, which is prevalently caused by iron deficiency. Maresin 1 (MaR1) is a novel docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. The aim of the present study was to investigate the therapeutic effects of MaR1 on iron-deficient anemia in IL-10 knockout (IL 10(-/-)) mice with spontaneous chronic colitis. METHODS: IL-10(-/-) mice of 16 weeks of age with established colitis were used for the experiments with MaR1 treatment for 2 weeks. Histologic injury, CD4+ lymphocyte values in the lamina propria, blood hemoglobin, hematocrit, serum iron concentrations, transferrin saturation, splenic iron stores, levels of inflammatory cytokines, expression of liver hepcidin mRNA, and western blotting of STAT3 were analyzed in this study. RESULTS: MaR1 treatment (0.3 ng/mouse) effectively attenuated histological colitis typically associated with decreased CD4+ lymphocytes in the lamina propria as well as the concentrations of MPO, TNF-alpha, IFN-gamma, IL-6 and IL 17 (P<0.05). Furthermore, reduced expression of liver hepcidin mRNA and p-STAT3 expression, as well as increased hemoglobin concentration, hematocrit, levels of serum iron, transferrin saturation and splenic iron stores were found in IL-10(-/ ) mice after MaR1 treatment (P<0.05). CONCLUSIONS: These results indicate that MaR1 treatment ameliorates iron-deficient anemia by reducing colonic inflammation and inhibiting hepcidin expression though the IL-6/STAT3 pathway. PMID- 27398159 TI - The important application of thioridazine in the endometrial cancer. AB - BACKGROUND: Endometrial cancer (ECa) is one of the serious healthy burden for female worldwide. The treatments of ECa focus on the application of endocrine therapy and aberrant signaling proteins expression recently years. Medroxyprogesterone acrtate (MPA) plays crucial role in the endocrine therapy for ECa patients. However, the outcomes are still not ideal in the advanced stage tumor, especially in the progesterone-resistant ECa. Thioridazine (THIO) is an anti-psychotic agent, which has been reported to suppress the development of several human cancers. In this study, we aimed at to explore the clinical significant of THIO in the treatment of ECa. METHODS: Two ECa cell lines (ISK and KLE) were enrolled in this study, and were grouped into fore groups based on the treatment with different agents. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to analyze the viability of ECa cell lines. The apoptosis of ECa cells was examined by using the flow cytometer. To investigate the expression of important proteins, we applied the quantitative real-time RT-PCR (qRT-PCR) method and western blot analysis. RESULTS: The viability of ECa cells was downregulated, and the apoptosis of ECa cells was upregulated after treating with the THIO plus MPA. The expression of progesterone receptor B (PRB) and dopamine receptor D2 (DRD2) were increased, and epidermal growth factor receptor (EGFR) and p-AKT were decreased in the THIO+MPA group. All these results suggested that the THIO could promote MPA to inhibit the growth of cells in ECa, especially in the progesterone-resistant ECa. CONCLUSION: Taken together, all the data in the present study suggested that the THIO plus MPA might act as the suppressor of tumor growth in ECa by inhibiting the PI3K/AKT signal transduction pathway, which was mediated by PRB, DRD2 and EGFR. PMID- 27398160 TI - FSCB phosphorylation regulates mouse spermatozoa capacitation through suppressing SUMOylation of ROPN1/ROPN1L. AB - Fibrous sheath CABYR binding protein (FSCB) is regulated by protein kinase A (PKA)-mediated tyrosine phosphorylation in the spermatozoa capacitation. Recently, we showed that FSCB phosphorylation activated spermatozoa motility. Nevertheless, the underlying mechanisms have not been completely elucidated. Here, we showed that FSCB phosphorylation inhibited SUMOylation of two crucial proteins ROPN1/ROPN1L that are associated with PKA/A kinase activity and spermatozoa motility. Suppression of SUMOylation of ROPN1/ROPN1L mimicked the effects of FSCB phosphorylation on spermatozoa motility. Immunoprecipitation assay showed that phosphorylated FSCB had a significantly higher affinity to ROPN1/ROPN1L than non-phosphorylated FSCB. Together, our data suggest that FSCB phosphorylation may regulate mouse spermatozoa capacitation through suppressing SUMOylation of ROPN1/ROPN1L, which sheds new light on creating a therapeutic strategy targeting FSCB phosphorylation in the study of infertility. PMID- 27398161 TI - miR-526b-3p functions as a tumor suppressor in colon cancer by regulating HIF 1alpha. AB - HIF-1alpha is an important transcriptional factor, which plays roles in cancer development and progression. But its regulation by miRNAs is not clear. Here, to investigate the regulation of HIF-1alpha by miRNAs, miRNAs were predicted and miR 526b-3p was verified as a regulator of HIF-1alpha in colon cancer cells. Using TaqMan RT-PCR analysis, we analyzed the expression of miR-526b-3p in tumor tissues and cell lines and found that miR-526b-3p was consistently under expressed in cancer tissues and cell lines compared with their normal controls. When miR-526b-3p was induced into the colon cancer cells, cell proliferation, metastasis and glycolysis of colon cancer cells were suppressed. We also found that miR-526b-3p was down-regulated in metastatic colon cancer tissues and negatively with HIF-1alpha mRNA in colon cancer tissues. In a summary, miR-526b 3p plays as a tumor suppressor by down-regulation of HIF-1alpha expression in colon cancer and may be a new diagnosis or therapeutic target. PMID- 27398162 TI - Silencing MRP1-4 genes by RNA interference enhances sensitivity of human hepatoma cells to chemotherapy. AB - AIM: Besides surgical treatment, systematic chemotherapy plays a crucial role in HCC treatment, especially for patients with advanced HCC. However, none of the single-drug-treatment strategies have shown significant survival benefit due to a high incidence rate of chemoresistance. This study was designed to observe the effect of small interfering of RNA (SiRNA) targeting multidrug resistance-related protein 1-4 (MRP1, MRP2, MRP3, and MRP4) in modulating drug resistance of HepG2/ADM and SMMC7721/ADM cells. METHODS: HepG2/Adriamycin (ADM) and SMMC7721/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity and half inhibitory concentration (IC50) of drugs was calculated. Flow cytometry was employed to analyze cell cycle distribution. MRP1-4 mRNA expression levels were measured by quantitative real-time PCR (QRT-PCR). Expression of proteins was analyzed by Western blot. The growth curve was draw and the cell apoptosis was also observed. Animal experiment was used to compare the cell growth. RESULTS: MTT assay showed that the values of IC50 and RI of HepG2/ADM and SMMC7721/ADM decreased after siRNA treatment in HepG2/ADM cells and SMMC7721/ADM cells. QRT-PCR analysis demonstrated the MRP1-4 mRNA expression decreased significantly in HepG2/ADM cells and SMMC7721/ADM cells after siRNA transfection. In addition, compared with parental cells, MRP1-4 protein expressions apparently decreased in SMMC7721/ADM and HepG2/ADM cells. Flow cytometry showed significantly elevated apoptosis rate following MRP1-4 siRNA transfection. Animal experiment suggested that silencing MRP1-4 gene in vivo inhibited tumor growth. CONCLUSION: Inhibition of MRP1-4 by small interfering RNA enhanced and selectively restored sensitivity of hepatoma cells to drugs. MRP1-4 siRNA might represent a new therapeutic option for HCC. PMID- 27398164 TI - MicroRNA-322 protects hypoxia-induced apoptosis in cardiomyocytes via BDNF gene. AB - BACKGROUND: Cardiomyocytes apoptosis under hypoxia condition contributes significantly to various cardiovascular diseases. In this study, we investigated the role of microRNA-322 (miR-322) in regulating hypoxia-induced apoptosis in neonatal murine cardiomyocytes in vitro. METHOD: Cardiomyocytes of C57BL/6J mice were treated with hypoxia condition in vitro. Cardiomyocyte apoptosis was measured by TUNEL assay. Gene expression pattern of miR-322 was measured by qRT PCR. Stable downregulation of miR-322 in cardiomyocytes were achieved by lentiviral transduction, and the effect of miR-322 downregulation on hypoxia induced cardiomyocyte apoptosis was investigated. Possible regulation of miR-322 on its downstream target gene, brain derived neurotrophic factor (BDNF) was investigated in cardiomyocytes. BDNF was then genetically silenced by siRNA to evaluate its role in miR-137 mediated cardiomyocyte apoptosis protection under hypoxia condition. RESULTS: Under hypoxia condition, significant apoptosis was induced and miR-322 was significantly upregulated in cardiomyocytes in vitro. Through lentiviral transduction, miR-322 was efficiently knocked down in cardiomyocytes. Downregulation of miR-322 protected hypoxia-induced cardiomyocyte apoptosis. Luciferase assay showed BDNF was the target gene of miR-322. QRT-PCR showed BDNF expression was associated with miR-322 regulation on hypoxia-induced cardiomyocyte apoptosis. Silencing BDNF in cardiomyocyte through siRNA transfection reversed the protective effect of miR-322 downregulation on hypoxia induced apoptosis. CONCLUSION: Our study revealed that miR-322, in association with BDNF, played important role in regulating hypoxia-induced apoptosis in cardiomyocyte. PMID- 27398163 TI - Birth of MTH1 as a therapeutic target for glioblastoma: MTH1 is indispensable for gliomatumorigenesis. AB - Malignant glioma is the most common primary tumor of the central nervous system. Chemotherapy and radiotherapy are the most common therapeutic approaches in glioma therapy. Both processes mainly kill cancer cells through generating high Reactive Oxygen Species (ROS) and lead to oxidative DNA damage. However, tumor resistance to ROS is always a challenge for cancer treatment. Human Mut T homolog 1 (MTH1, also known as NUDT1) is regarded as a protector of nucleotides against oxidization. Recent reports have verified that overexpression of MTH1 could remove oxidized dNTP pools. Here, we find that MTH1 is overexpressed both at mRNA and protein levels in GBM. MTH1 silencing inhibits colony formation; tumor spheres formation and xenograft tumor growth, and more importantly, the viability of glioma cells is significantly decreased in H2O2 after MTH1 was knocked down in glioma. PI staining show that H2O2 cause more glioma cell death after MTH1 silencing. So we speculate that overexpression of MTH1 is crucial for glioma survival, suppression of its expression can inhibit cancer cell survival in vitro and in vivo, MTH1 may be a potential target for human glioma therapy in future. PMID- 27398165 TI - Anticytoproliferative effect of Vitamin C on rat hepatic stellate cell. AB - This study was conducted to investigate the potential therapeutical benefit of Vitamin (VC), a potent antioxidant, on suppressing proliferation of immortalized rat liver stellate cell line (HSC-T6) in vitro, and to discuss the underlying mechanism. HSC-T6 was co-treated with different concentrations of VC (50, 100, 200 MUmol/L) on designed time points. Then, cell viability was assessed by using MTT analysis, and the changes of cytomorphology was observed with apoptosis specific TUNEL and immunohistochemical stains, as well as the intracellular target genes was determined by using RT-PCR, respectively. As the outcomes, VC treated HSC-T6 showed significantly inhibited cell growth in a dose-dependent manner when compared to the vehicle control. Cytologically, VC increased TUNEL labeled positive cells in cultured HSC-T6, which the cell count was greater than vehicle control. Meanwhile, VC-treated HSC-T6 showed elevated immunoreactive for TGF-beta1-labeled cells. Moreover, VC contributed to down-regulated expressions of intracellular c-myc, cyclin D1, mTOR mRNAs in HSC-T6. Collectively, these preliminary findings have demonstrated that VC-mediated anti-proliferative effect on HSCs is involved in molecular mechanisms of promoting apoptosis and blocking endogenous collagenation. PMID- 27398166 TI - Extracorporeal membrane oxygenation improves survival in a novel 24-hour pig model of severe acute respiratory distress syndrome. AB - Extracorporeal membrane oxygenation (ECMO) is increasingly being used to treat severe acute respiratory distress syndrome (ARDS). However, there is limited clinical evidence about how to optimize the technique. Experimental research can provide an alternative to fill the actual knowledge gap. The purpose of the present study was to develop and validate an animal model of acute lung injury (ALI) which resembled severe ARDS, and which could be successfully supported with ECMO. Eighteen pigs were randomly allocated into three groups: sham, ALI, and ALI + ECMO. ALI was induced by a double-hit consisting in repeated saline lavage followed by a 2-hour period of injurious ventilation. All animals were followed up to 24 hours while being ventilated with conventional ventilation (tidal volume 10 ml/kg). The lung injury model resulted in severe hypoxemia, increased airway pressures, pulmonary hypertension, and altered alveolar membrane barrier function, as indicated by an increased protein concentration in bronchoalveolar fluid, and increased wet/dry lung weight ratio. Histologic examination revealed severe diffuse alveolar damage, characteristic of ARDS. Veno-venous ECMO was started at the end of lung injury induction with a flow > 60 ml/kg/min resulting in rapid reversal of hypoxemia and pulmonary hypertension. Mortality was 0, 66.6 and 16.6% in the SHAM, ALI and ALI + ECMO groups, respectively (p < 0.05). This is a novel clinically relevant animal model that can be used to optimize the approach to ECMO and foster translational research in extracorporeal lung support. PMID- 27398167 TI - Expression of COL6A1 predicts prognosis in cervical cancer patients. AB - COL6A1 has been shown to play an important role in tumor initiation and progression. The present study is to investigate the clinical significance of COL6A1 in cervical cancer. In this study, the COL6A1 expression levels in 10 paired cervical cancer tissues and the adjacent non-tumor tissues were examined by real-time PCR. The expression of COL6A1 protein was examined in 162 cervical cancer samples by immunohistochemistry, and the correlation of COL6A1 expression with clinicopathologic factors was analyzed. The overall and recurrent-free survival rates were estimated using Kaplan-Meier method and compared with the log rank test. The prognostic analysis was carried out with multivariate Cox regressions model. The result showed that COL6A1 expression was up-regulated in cervical cancer tissues in compared with that in non-tumor tissues. High expression of COL6A1 was significantly correlated with FIGO stage (P<0.001), tumor size (P=0.025) and lymph node metastasis (P=0.028) of the disease. Moreover, survival analysis showed that high expression of COL6A1 was significantly associated with poorer overall (OS) and recurrent free (RFS) survival (p=0.004 and =0.001, respectively) of cervical cancer patients. Multivariate analysis suggested that COL6A1 expression was an independent prognostic marker of cervical cancer (P=0.029). Thus, COL6A1 may serve as an oncogene in the initiation and progression of cervical cancer, and as a predictor of poor prognosis in cervical cancer patients. PMID- 27398168 TI - Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer. AB - Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed that DDR2 mRNA expression was upregulated in ovarian cancer tissues compared with normal ovary tissues. Statistical analysis revealed that DDR2 expression correlated with tumor stage (P = 0.008) and peritoneal metastasis (P = 0.009). Patients with high DDR2 expression showed poorer 5-year overall survival (P = 0.005), and DDR2 remained an independent prognostic marker for OS (P = 0.013) in multivariate analysis. Our results suggest that DDR2 might be closely associated with ovarian cancer progression and metastasis. Its high expression may serve as a potential prognostic biomarker in human ovarian cancer. PMID- 27398169 TI - Mutational analysis of ATP7B in Chinese Wilson disease patients. AB - Wilson Disease (WD) is an inborn error of copper metabolism inherited in an autosomal recessive manner caused by the mutations in the P-type ATPase gene (ATP7B). In this study, we screen and detect the mutations of the ATP7B gene in unrelated Chinese WD patients. A total of 68 individuals from ten provinces of China with WD were recruited. Of them, 43 were males and 25 were females, and their onset ages were from 1 to 48 years with a median onset age of 22.2 years. All the exons and exon/intron boundaries of ATP7B gene of the patients were sequenced and aligned to the referred ATP7B gene sequence. The results suggested that 66 of the 68 patents carried with at least one mutation and 48 different mutations were identified including 34 missense, one synonymous, two nonsense, two splicing, and nine frameshift mutations (five insertion and four deletion). Among these mutations, c.2333G>T, c.2310C>G, c.2975C>T, and c.3443T>C were the most prevalent mutants and c.2310C>G always linked with c.2333G>T. The eighth, 11(th), and 18(th) exons carried more mutations (6/48, 5/48, and 5/48, respectively) than others. After comparing with the mutations reported previously, 22 out of the 48 mutations were identified as novel mutations. A popular algorithm, Polyphen-2, was used to predict the effects of the amino-acid substitution due to the mutations on the structure and function of ATP7B function and the predicted results indicated that all the missense mutations were unfavorable except c.121A>G and c.748G>A. Phenotype/genotype correlation analysis suggested that the patients with c.2975C>T or c.3809A>G often presented WD features before 12 years old while the patients with c.3443T>C almost presented WD after 12 years old. This is the first time to identify the common mutations contributing to early onset age in Chinese WD patients. Our study will broaden our knowledge about ATP7B mutations in WD patients. PMID- 27398170 TI - Comparative evaluation of antimicrobial efficacy of three herbal irrigants in reducing intracanal E. faecalis populations: An in vitro study. AB - BACKGROUND: The present study aimed to evaluate the intracanal bacterial reduction promoted by chemomechanical preparation using three different herbal extracts named Ocimum sanctum (OS), Cinnamomum zeylanicum (CZ), Syzygium aromaticum (SA) against Enterococcus faecalis. MATERIAL AND METHODS: Root canals from extracted teeth were contaminated with Enterococcus faecalis ATCC 29212 for 7 days and then randomly distributed into 3 experimental groups of 10 teeth each: which includes conventional irrigation with OS, CZ and SA. The control groups included 5 teeth each consisting of NaOCl (positive control) and distilled water (negative control). Samples taken before and after chemomechanical procedures were cultured, and the colony-forming units (CFUs) were counted. Bacterial identification was performed using Polymerase chain reaction technique. The statistical analyses were performed with various tests. RESULTS: Reduction in the intracanal bacterial populations was highly significant for all the experimental groups. CZ and SA showed 80 to 85% intracanal bacterial reduction while O. Sanctum revealed only 70 to 75 % reduction. NaOCl showed 96 to 100 % bacterial reduction on the other hand distilled water showed very minimal bacterial reduction i.e 10 to 16%. CONCLUSIONS: Cinnamomum zeylanicum, Syzygium aromaticum and Ocimum sanctum showed intracanal bacterial reduction against Enterococcus faecalis. The 3 experimental groups were less effective in terms of intracanal bacterial reduction as compare to NaOCl but more effective than distilled water. KEY WORDS: Antimicrobial activity, Cinnamomum zeylanicum, Enterococcus faecalis, Ocimum sanctum, Syzygium aromaticum, herbal extracts. PMID- 27398171 TI - CD166 expression in dentigerous cyst, keratocystic odontogenic tumor and ameloblastoma. AB - BACKGROUND: CD166 is a glycoprotein of an immunoglobulin super family of adhesion molecules that has been associated with aggressive characteristics and high recurrence rate of tumors. Different odontogenic lesions exhibit considerable histological variation and different clinical behavior. In an attempt to clarify the mechanisms underlying this different behavior, the present study investigates the immunohistochemical expression of CD166 in these lesions. MATERIAL AND METHODS: In this study 69 formalin-fixed, paraffin embedded tissue blocks of odontogenic lesion consist of 15 unicystic ameloblastoma (UA), 17 solid ameloblastoma (SA), 18 keratocystic odontogenic tumors (KCOT), and 19 dentigerous cysts (DC) were reviewed by immunohistochemistry for CD166 staining. RESULTS: In this study, CD166 immune staining was evident in all specimen groups except dentigerous cyst. In positive cases, protein localization was cytoplasmic and/or membranous. CD166 expression was seen in76.5% (13) of SA, 73.5% (11) of UA, and 66.7% (12) of KCOTs. Statistical analysis showed that CD166 expression levels were significantly higher in ameloblastoma (SA and UA) and KCOTs than dentigerous cyst (P <0.001), but there was no statistically significant difference between CD166 expression in the other groups (P>0.05). CONCLUSIONS: This data demonstrates that overexpression of CD166 may have a role in the pathogenesis of ameloblastoma and KCOT. KEY WORDS: CD166, ameloblastoma, dentigerous cyst, odontogenic keratocyst. PMID- 27398172 TI - Evaluation of the Diode laser (810nm,980nm) on dentin tubule diameter following internal bleaching. AB - BACKGROUND: The aim of this study was to evaluate the effect of diode laser irradiation and bleaching materials on the dentinal tubule diameter after laser bleaching. MATERIAL AND METHODS: The dentin discs of 40 extracted third molar were used in this experiment. Each disc surface was divided into two halves by grooving. Half of samples were laser bleached at different wavelengths with two different concentrations of hydrogen peroxide. Other half of each disc with no laser bleaching remained as a negative control. Dentin discs were assigned randomly into four groups (n=10) with following hydrogen peroxide and diode laser wavelength specifications; Group 1 (30% - 810 nm), group 2 (30% - 980 nm), group 3 (46% - 810 nm) and group 4 (46% - 980 nm). All specimens were sent for scanning electron microscopic (SEM) analysis in order to measure tubular diameter in laser treated and control halves. Data were analyzed by ANOVA and Tukey test (p<0.05). RESULTS: A significant reduction in dentin tubule diameter was observed in groups 1, 2 and 4. There was no significant difference between groups 1 and 2 and between groups 3 and 4 after bleaching. CONCLUSIONS: The SEM results showed that diode laser was able to reduce dentin tubule diameter and its effect on dentin was dependent on chemical action of bleaching material. KEY WORDS: Laser, diode, dentin, tubule, diameter. PMID- 27398173 TI - Effect of root canal rinsing protocol on dentin bond strength of two resin cements using three different method of test. AB - BACKGROUND: Different studies have used different tests to evaluate bond strength of resin cements to root dentin. In this in vitrostudy, three different tests were used to evaluate the bond strength of two resin cements to root dentin using two root dentin irrigation protocols. MATERIAL AND METHODS: Ninety-six intact single-rooted teeth were selected for this study. Forty-eight teeth, with a root length of 15mm, were randomly divided into two groups and irrigated with normal saline or 2.5% sodium hypochlorite solutions during root canal preparation, respectively. For each 12 specimens from each group, fiber post #1 was bonded using an etch-and-rinse (Duo-Link) and a self-adhesive (BisCem) resin cement, respectively. After incubation, two specimens were prepared for the push-out test from the middle thirds of the roots. In another 24 teeth, after two 1.5-mm sections were prepared from the middle thirds of the prepared roots, sections of the post were bonded in two subgroups with each of the cements mentioned above and the samples were prepared for the pull-out test. For shear test, the crowns of 48 teeth were cut away, the dentin surfaces were prepared, the two irrigation solutions were used, and the resin cements were bonded. Data collected from the three tests were evaluated by ANOVA, post-hoc Tukey and Weibull tests (alpha=0.05). RESULTS: There were significant differences in the mean bond strength values between the three bond strength tests (P<0.001). Rinsing protocol and cement type resulted in similar variations in the mean bond strength in all tests (P>0.05). CONCLUSIONS: Under the limitations of the present study, the method of the test used had an effect on the recorded bond strength between the resin cement and root dentin. Cement type and irrigation protocol resulted in similar variations with all the tests. Push-out and shear tests exhibited more coherent results. KEY WORDS: Bond strength, endodontically treated tooth, fiber post, resin cement, sodium hypochlorite. PMID- 27398174 TI - Evaluation of primary stability of innovated orthodontic miniscrew system (STS): An ex-vivo study. AB - BACKGROUND: Stability is determined as one of the requirements in use of Temporary Anchorage Devices (TAD) in orthodontics. Miniscrew has been a widely used Bone Anchor. Compared with mini-implant that necessitates osseointegration; mechanical retention is a determining factor for primary stability of miniscrew. Studies investigated various ways to increase primary stability. The aim of this study is to introduce a new configuration of miniscrew system which is believed to obtain more primary stability. MATERIAL AND METHODS: Freshly ovine mandibles were cut in blocks. Twenty-seven miniscrews (diameter 1.6 * 8 mm; G2, Dual Top Anchor System, Jeil Medical, Seoul, Korea) were inserted in the blocks and divided in 2 experimental groups: single miniscrew and the innovated design "Seifi Twin Screw (STS)". Primary stability was evaluated by Periotest "M"(r) device. RESULTS: Independent t-test showed a significant difference between 2 experimental groups in periotest evaluation (p< 0.05). STS demonstrated higher primary stability due to its mechanical configuration and design. CONCLUSIONS: The STS provides higher primary stability and was found to be effective in increased success rate of miniscrew systems from the standpoint of primary stability. KEY WORDS: Anchorage procedures, anchorage techniques, orthodontic anchorage procedures, miniscrews, temporary anchorage device. PMID- 27398175 TI - Prevalence of root caries among elders living in residential homes of Bengaluru city, India. AB - BACKGROUND: Among the various oral ailments which have been observed in elderly, root caries is a significant one. Tooth loss is chief oral health-related negative variable to the quality of life in elderly and root caries is the major cause of tooth loss in them. It has been reported about a third of older population bears most of the root caries burden, so the present study aimed to assess the prevalence of root caries among older individuals residing in residential homes of Bengaluru city India. MATERIAL AND METHODS: Elderly individuals aged 60 and above, residing in residential homes of Bangalore city, were included in the study. The study participants filled a questionnaire regarding their demographic details and oral health habits. Root surface caries was recorded according to criteria described by Banting et al. and root caries was expressed in terms of the root caries index (RCI). The statistical analysis was performed using descriptive statistics and chi-square test. P < 0.05 was considered as statistically significant. RESULTS: The prevalence of root caries was 46.4%. The root caries index was 15%. Statistically significant differences (P < 0.05) observed across gender, marital status, diet, socio-economic status, medication, method of cleaning and frequency of cleaning and were identified as significant predictors of root caries. CONCLUSIONS: The prevalence of root caries among institutionalized older people was high. Oral health policies and preventive measures are needed focusing on the special needs of this neglected and socioeconomically deprived population to improve their quality of life. KEY WORDS: Elders, residential home, root caries. PMID- 27398176 TI - Effect of composite/amalgam thickness on fracture resistance of maxillary premolar teeth, restored with combined amalgam-composite restorations. AB - BACKGROUND: Combined amalgam-composite restorations have been used through many years to benefit from the advantages of both dental amalgam and composite resin. Two variations have been mentioned for this technique, this study investigated the fracture resistance of maxillary premolar teeth with extended mesio-occluso distal (MOD) cavities, restored with the two variations of combined amalgam composite restorations. MATERIAL AND METHODS: Sixty intact extracted premolar teeth were randomly divided into 6 groups (G1-G6) of 10 teeth. G1; consisted of intact teeth and G2; consisted of teeth with MOD preparations were assigned as the positive and negative control groups respectively. Other experimental groups after MOD preparations were as follows: G3, amalgam restoration; G4, composite restoration; G5 combined amalgam-composite restoration with amalgam placement only on 1mm of the gingival floor of the proximal boxes; G6, combined amalgam composite restoration with amalgam placement to the height of contact area of the proximal surface of the tooth. Fracture strength of the specimens was measured and the data were analyzed using one-way analysis of variance (ANOVA). The level of significance was P<0.05. Fracture mode of the specimens was also recorded. RESULTS: G1 had the highest value of fracture resistance (1736.90 N). G2 and G3 had the lowest fracture resistance (775.70 N and 874.70 N, respectively). The difference between G 4, 5 and 6 was not statistically significant. However, G4, G5 and G6 showed significantly higher resistance to fracture compared to G2 and G3. Fracture modes were favorable in all of the study groups except in G6. CONCLUSIONS: Fracture resistance of the premolars restored with the two variations of combined amalgam-composite restoration was similar to that achieved with composite restoration alone and more than that of amalgam restoration alone. It can be concluded that the thickness of amalgam in combined amalgam-composite restorations did not affect fracture resistance of the teeth. KEY WORDS: Amalgam, composite, fracture resistance, restoration. PMID- 27398177 TI - "Evaluation of shear bond strength of a composite resin to white mineral trioxide aggregate with three different bonding systems"-An in vitro analysis. AB - BACKGROUND: Mineral trioxide aggregate (MTA) is a biomaterial that has been investigated for endodontic applications. With the increased use of MTA in pulp capping, pulpotomy, perforation repair, apexification and obturation, the material that would be placed over MTA as a final restoration is an important matter. As composite resins are one of the most widely used final restorative materials, this study was conducted to evaluate the shear bond strength of a composite resin to white mineral trioxide aggregate (WMTA) using three different bonding systems namely the two-step etch and rinse adhesive, the self-etching primer and the All-in-one system. MATERIAL AND METHODS: Forty five specimens of white MTA (Angelus) were prepared and randomly divided into three groups of 15 specimens each depending on the bonding systems used respectively. In Group A, a Two-step etch and rinse adhesive or 'total-etch adhesive', Adper Single Bond 2 (3M/ESPE) and Filtek Z350 (3M ESPE, St Paul, MN) were placed over WMTA. In group B, a Two-step self-etching primer system, Clearfil SE Bond (Kuraray, Medical Inc) and Filtek Z350 were used. In Group C, an All-in-one system, G Bond (GC corporation, Tokyo, Japan) and Filtek Z350 were used. The shear bond strength was measured for all the specimens. The data obtained was subjected to One way Analysis of Variance (ANOVA) and Scheffe's post hoc test. RESULTS: The results suggested that the Two-step etch and rinse adhesive when used to bond a composite resin to white MTA gave better bond strength values and the All-in-one exhibited the least bond strength values. CONCLUSIONS: The placement of composite used with a Two-step etch and rinse adhesive over WMTA as a final restoration may be appropriate. KEY WORDS: Composite resins, dentin bonding agents, mineral trioxide aggregate, shear bond strength. PMID- 27398178 TI - Physical evaluation of a new pulp capping material developed from portland cement. AB - BACKGROUND: This study examined the effects of addition of 10% and 25% by weight calcium hydroxide on the physicochemical properties of Portland cement associated with 20% bismuth oxide in order to develop a new pulp capping material. MATERIAL AND METHODS: The solubility, pH value, setting time, compressive strength, and push out bond strength of modified Portland were evaluated and compared to those of mineral trioxide aggregate (MTA) and Portland cement containing 20% bismuth oxide. RESULTS: The statistical analysis was performed with ANOVA and Duncan's post-hoc test. The results show that the strength properties and push out bond strength of Portland cement were adversely affected by addition of calcium hydroxide especially with a ratio of 25 wt%, however, the setting time and pH were not affected. MTA showed a statistically significant lower setting time than other cements (P<=0.001). Portland cement with bismuth oxide and Port Cal I showed a statistically significant higher Push out Bond strength than MTA and Port Cal II (P=0.001). CONCLUSIONS: Taking the setting time, push out bond strength and pH value into account, addition of 10 wt% calcium hydroxide to Portland cement associated with 20% bismuth oxide produces a new pulp capping material with acceptable physical and adhesive properties. Further studies are recommended to test this cement biologically as a new pulp capping material. KEY WORDS: Calcium hydroxide, MTA, Portland cement, setting time, solubility, strength. PMID- 27398179 TI - Fluoride release and uptake abilities of different fissure sealants. AB - BACKGROUND: The long-term capability of resin sealants and glass ionomer cements to release fluoride is associated to a reduction in pit and fissure caries. The regular use of fluoride varnishes/toothpastes can result in the absorption of fluoride into the sealant. The objective of the present study was to assess the fluoride release/uptake capacities of different fissure sealants. MATERIAL AND METHODS: Three different fissure sealants (Fuji Triage/GC, Fissurit FX/Voco and Grandio Seal/Voco) were examined. Ten discs of each material were prepared. Each disc was incubated with distilled water and then the solution analyzed for diluted for fluoride concentration, using a combination of fluoride electrode (OrionGP 1 S/N 13824, Orion Research Inc, Boston, MA, USA) connected to an expandable ion analyzer (Orion 720A, Orion Research Inc, Boston, MA, USA). Standard curves between 1 and 100 ppm F- were used to calibrate the electrode. Cumulative fluoride release was measured on days 1, 2, 3, 5, 7, 21, 35 and 49, then two different fluoride varnishes/pastes (Profluorid Varnish/Voco, MI Paste Plus/GC), were applied to the sealants tested, and fluoride release (after reuptake) was measured on days 56, 70 and 84. RESULTS: Kruskal Wallis test confirmed significant differences in fluoride release between Fuji Triage/GC and Fissurit FX/Voco and Grandio Seal/Voco from day 1 (P < 0.001). The application of fluoride varnish Profluorid Varnish enhanced the fluoride release for all sealants (P < 0.05). MI Paste Plus enhanced the fluoride release for all sealants except for Fuji Triage/GC (P > 0.05). CONCLUSIONS: The GIC-based sealant (Fuji Triage/GC) released significantly more fluoride than the resin sealants tested. The exposure to the fluoridated varnish (Profluorid Varnish) significantly recharged the sealants tested more than the CPP-ACPF toothpaste (MI Paste Plus). KEY WORDS: Fissure sealants, fluoride release, fluoride uptake, glass ionomer cements. PMID- 27398180 TI - Six-month healing success rates after endodontic treatment using the novel GentleWaveTM System: The pure prospective multi-center clinical study. AB - BACKGROUND: This prospective multi-center (PURE) clinical study evaluated healing rates for molars after root canal treatment employing the GentleWave(r) System (Sonendo, Inc., Laguna Hills, CA). MATERIAL AND METHODS: Eighty-nine patients met the inclusion criteria and consented for this clinical study after referral for a root canal treatment. All enrolled patients were treated with the GentleWave System. Five endodontists performed the clinical procedures and follow-up evaluations. Pre-operative, intra-operative, and post-operative data were collected from the consented patients. Each patient was evaluated for clinical signs and symptoms. Two trained, blinded, and independent evaluators scored the subject tooth radiographs for apical periodontitis using the periapical index (PAI). The teeth classified as healing or healed were considered as a success and composed of a cumulative success rate of healing. Statistical analysis was performed by using the Fisher's exact test, Pearson correlation, and multivariate logistic regression analyses of the pre-operative prognostic factors at 0.05 significance level. RESULTS: Seventy-seven patients were evaluated at six months with a follow-up rate of 86.5%. The cumulative success rate of healing was 97.4%. Eleven prognostic factors were identified using bivariate analyses. Using logistic analyses, the two prognostic significant variables that were directly correlated to healing were the pre-operative presence of periapical index (p value=0.016), and single treatment visits (p value=0.024). CONCLUSIONS: In this six-month PURE clinical study, the cumulative success rate of healing was 97.4% when patients were treated with the GentleWave(r) System. KEY WORDS: Healing rate, root canal treatment, molar, GentleWaveTM, Sonendo(r), Multisonic UltracleaningTM . PMID- 27398181 TI - Expression of claudin-5, claudin-7 and occludin in oral squamous cell carcinoma and their clinico-pathological significance. AB - BACKGROUND: Claudin and occludin are the important tight junctions protein in human. The downregulation or upregulation of claudins and occludin might have a role in cancer development. The objective of this study was to investigate the expression of claudin-5, claudin-7 and occludin in oral squamous cell carcinoma (OSCC) and their relationships with the prognostically-related clinico-pathologic features. MATERIAL AND METHODS: Standard indirect immunohistochemical technique using anti-claudin-5, anti-claudin-7 and anti-occludin was performed in formalin fixed paraffin-embedded tissue sections of 66 OSCC samples from Faculty of Dentistry, Chulalongkorn University. The positive cases were divided into 2 groups, the low expression group (cases with less than 50% of positive cancer cells) and the high expression group for statistical analysis. Categorical analysis of the clinico-pathologic parameters together with univariate analysis using the Kaplan-Meier method and the log rank test were performed. RESULTS: There were 22 male and 23 female patients enrolled in this study, with a mean age of 65.82+12.10 years. The claudin-5 immunoreactivity was observed in 26.6% of cases. The positive immunoreactivity of claudin-7 is more noted (93.3%). Only 4 cases showed occludin immunoreactivity (8.9%) and all of them show positivity less than 25% of cancer cells. Only loss of claudin-7 expression was associated with the high pathologic grade, advanced TNM staging, large tumor size, the presence of microscopic perineural, vascular invasions and regional lymph node involvement. There is a tendency towards the association of the higher claudin-7 expression and a longer survival time (P=0.012). CONCLUSIONS: The results showed expression of claudin-5, claudin-7 and low expression of occludin in OSCC. Only claudin-7 expression showed impact on clinic-pathological parameter of OSCC. KEY WORDS: Claudin, occludin, oral squamous cell carcinoma, tight junctions, oral cancer. PMID- 27398182 TI - Biomechanical evaluation of oversized drilling technique on primary implant stability measured by insertion torque and resonance frequency analysis. AB - BACKGROUND: This study evaluated the influence of implant site preparation depth on primary stability measured by insertion torque and resonance frequency analysis (RFA). MATERIAL AND METHODS: Thirty-two implant sites were prepared in eight veal rib blocks. Sixteen sites were prepared using the conventional drilling sequence recommended by the manufacturer to a working depth of 10mm. The remaining 16 sites were prepared using an oversize drilling technique (overpreparation) to a working depth of 12mm. Bone density was determined using cone beam computerized tomography (CBCT). The implants were placed and primary stability was measured by two methods: insertion torque (Ncm), and RFA (implant stability quotient [ISQ]). RESULTS: The highest torque values were achieved by the conventional drilling technique (10mm). The ANOVA test confirmed that there was a significant correlation between torque and drilling depth (p<0.05). However, no statistically significant differences were obtained between ISQ values at 10 or 12 mm drilling depths (p>0.05) at either measurement direction (cortical and medullar). No statistical relation between torque and ISQ values was identified, or between bone density and primary stability (p >0.05). CONCLUSIONS: Vertical overpreparation of the implant bed will obtain lower insertion torque values, but does not produce statistically significant differences in ISQ values. KEY WORDS: Implant stability quotient, overdrilling, primary stability, resonance frequency analysis, torque. PMID- 27398183 TI - Repeated exposure of acidic beverages on esthetic restorative materials: An in vitro surface microhardness study. AB - BACKGROUND: A manifold increase in the consumption of aerated beverages has witnessed a twin increase in tooth wear and raised demand for esthetic restorative materials. This study aimed to evaluate the surface microhardness changes of esthetic restorative materials following treatment with aerated beverages in an in-vitro situation. MATERIAL AND METHODS: The initial surface microhardness of the restorative materials GC Fuji II LC, GC Fuji IX, Nano Glass ionomer, Resin and Nano composite was recorded. These materials were studied under 3 groups that included those exposed to the acidic beverages daily, weekly once in a month and those that had no exposures at all. The final surface microhardness of the materials was recorded following experimentation and was subjected to statistical comparisons. RESULTS: The restorative materials were compared for their surface microhardness changes following respective treatments using the T-test and One-way ANOVA analysis. Inter-comparisons between the groups showed statistical significance (p<.05), when treated with both the beverages. The five restorative materials revealed surface microhardness loss; the maximum reduction noticed with the Nano glass ionomer cement tested (p<.0005). CONCLUSIONS: The surface microhardness of restorative materials markedly reduced upon repeated exposures with acidic beverages; the product with phosphoric acid producing the maximum surface microhardness loss. KEY WORDS: Restorative materials, acidic beverages, surface microhardness, resin composites, glass ionomers. PMID- 27398184 TI - MTA apical barrier: In vitro study of the use of ultrasonic vibration. AB - BACKGROUND: The apexification is the first alternative treatment on a permanent tooth when, after a tooth trauma and in the presence of immature apex trauma, pulp necrosis occurs. Many studies have demonstrated the efficacy of mineral trioxide aggregate (MTA) as apical sealing material of choice in these cases, but has a degree of filtration as all other materials. The objective of this study was to analyze the seal ability of MTA on the duct walls in immature teeth unirradicular apexes, using indirect vibration. MATERIAL AND METHODS: The study was conducted on 45 teeth divided into 3 groups: Group A or control group in which no vibration for placing the MTA was used, Group B and C or groups where indirect vibration analysis was used. All samples were immersed in methylene blue to assess filtration. After performing longitudinal cuts millimetric measuring were made of the degree of filtration, divided into 3 degrees (2mm each grade filtration). RESULTS: Results obtained confirm our hypothesis, obtaining lesser degree of filtration those groups in which indirect vibration (Groups B and C) was performed. It was shown that the degree of filtration is closely linked to the degree of adaptation. CONCLUSIONS: MTA vibration offers better results in its adaptation to the canal walls, significantly reducing the degree of filtration. KEY WORDS: Apexification, MTA, filtration, indirect vibration. PMID- 27398185 TI - Comparative evaluation of shear bond strength of three flowable compomers on enamel of primary teeth: An in-vitro study. AB - BACKGROUND: The aim of the present study was to determine Shear bond strength (SBS) of different flowable compomers on the enamel surface of primary teeth. The null hypothesis to be tested was that none of the flowable compomer would differ significantly from the other two with respect to SBS. As a result, the tested materials that have the easiest application on child patient is preferred. MATERIAL AND METHODS: Sixty newly extracted non carious primary molars were selected. The buccal surface was cleaned and polished to obtain a flat enamel surface. The specimens were randomly divided into three groups of 20 teeth each, based on the flowable compomers applied, as follows: group I: Dyract Flow(r) (Dentsply, Konstanz, Germany); group II: Twinky Star Flow(r) (Voco, Cuxhaven, Germany); and group III: R&D Series Nova Compomer Flow(r) (Imicryl, Konya, Turkey). RESULTS: SBS in group II (6.78+/- 0.45 MPa) were significantly lower than groups I and III (8.30 +/- 0.29 and 8.43 +/- 0.66 MPa, respectively) (P<.001). No significant difference was found between groups I and III (P<.05). CONCLUSIONS: Significant differences existed between the SBS of the groups. Therefore, the null hypothesis was rejected. Flowable compomers can provide adequate SBS with self-etching system at restoration of primary teeth. Thus, successful restorations in pediatric patients can be done in a practical way. KEY WORDS: Flowable compomer, primary teeth, shear bond strength. PMID- 27398186 TI - Pathogenesis and clinicohistopathological caractheristics of melanoacanthoma: A systematic review. AB - INTRODUCTION: The melanoacanthoma is a rare benign pigmented tumor, characterized by a fast radial growth and clinical behavior similar to melanoma. Color changes in oral mucosa and dermis are consequence of increased melanocyte activity as response to an irritant factor. There is a vast phenotypic variety. It is difficult to distinguish between a benign pigmented lesion and a melanoma at its early stage. Due to its clinical relevance is crucial to diagnose possible malignancy of the lesions. OBJECTIVES: The aim of this article is to conduct a systematic review of all published articles, as well as update and evaluate etiologic factors and clinicopathological features. MATERIAL AND METHODS: We carried out a search in the Medline database (PubMed) using the key words "oral melanoacanthoma" AND "oral melanoacanthosis" AND "oral melanoepithelioma". Inclusion criteria were all published articles since its discovery. Demographic data, histological features and immunohistochemical findings were extracted from the full articles. RESULTS: A total of 56 articles were analysed. 114 injuries drawn from these articles were studied, a total of 115 injuries with our contribution case. The 74.78% of authors claim a reactive pathogenesis. The average age of lesion appearance is 34.79 years, with an age range of 5-87 years. There is a predominance of the female sex in solitary phenotype 3: 2 and a ratio of women to men 5: 3 if it is multifocal phenotype. Bilateral phenotype is slight higher in women of 2: 1. CONCLUSIONS: Histopathological analysis of the lesion is vital to diagnose malignancy. Therefore, any heterogeneous, pigmented lesion with irregular edges, raised surface, fast growth and abrupt appearance should be biopsied. More emphasis on the potential irritants should also be put to improve the quality of life of our patients and to reduce morbidity of melanoacanthoma, as well as, several similar clinical behavior disease. KEY WORDS: Melanoacanthoma, oral cancer, diagnosis. PMID- 27398187 TI - Oral health in children with physical (Cerebral Palsy) and intellectual (Down Syndrome) disabilities: Systematic review I. AB - INTRODUCTION: Traditionally, patients with physical and/or intellectual disabilities presented greater oral pathology, owing to their condition and to other external factors. Improved social and health conditions make it necessary to update knowledge on their oral and dental health. MATERIAL AND METHODS: For this purpose, a bibliographic review was done regarding the state of oral health of children with these two types of disability, in comparison with a control group. Some of the guidelines of the PRISMA statement were taken into account. The ranking of the articles found is based on the modified Newcastle-Ottawa Quality Assessment Scale. The final number of articles evaluated was 14. Parameters such as dental caries, oral hygiene, gingival health, dental traumas, malocclusion and habits were considered. RESULTS: There is no consensus among authors regarding dental caries, oral hygiene and gingival health. The different results obtained are due in part to the fact that the methodologies used were not the same. However, it has been noted that, when studying other parameters and regardless of the methodology employed, the results obtained are similar. CONCLUSIONS: Children with physical and intellectual disabilities constitute a group that needs early and regular dental care in order to prevent and limit the severity of the pathologies observed. KEY WORDS: Oral health, dental caries, malocclusion, oral habits, dental trauma, oral hygiene, disabled child, cerebral palsy and Down syndrome. PMID- 27398188 TI - Incidence of oral health in paediatric patients with disabilities: Sensory disorders and autism spectrum disorder. Systematic review II. AB - INTRODUCTION: We are currently witnessing an increase in the number of disabled patients, creating the need for knowledge of each of the pathologies and of the different oral and dental conditions they present, in order to achieve efficient management and treatment. OBJECTIVES: To analyse the existing scientific literature on the oral conditions of children with autism spectrum disorder (ASD) and children with sensory deficits (SD), in comparison with the healthy child population. MATERIAL AND METHODS: The bibliographic search was carried out in Pubmed/Medline, Scopus and Cochrane Library and included articles taking a sample of children between 0 and 18 years of age diagnosed with the abovementioned disorders and including at least one of the following oral hygiene conditions - oral hygiene, dental caries, malocclusion, oral habits, dental trauma, and gingival-periodontal status - comparing them with a healthy population. RESULTS: A total of 10 articles were obtained for autism spectrum disorder and six for sensory deficits. CONCLUSIONS: Of all the variables studied, only the state of oral, gingival and/or periodontal hygiene can be considered worse in patients with ASD and SD, although we believe a larger number of research studies is needed to corroborate these results. KEY WORDS: Oral health, dental caries, malocclusion, oral habits, dental trauma, oral hygiene, disabled child, autism, autism spectrum disorder, deaf, blind. PMID- 27398189 TI - Traumatic arteriovenous fistula as consequence of TMJ arthroscopic surgery. A case report. AB - The ocurrence of a traumatic arteriovenous fistula after arthroscopic surgery of TMJ represents an extremely rare event. Specifically, this uncommon complication has been described only in a few case reports. In this light, the most frequent symptoms showed by this disease are thrills, bruits, pulsatile tinnitus, and an expansible vascular mass. Importantly, the severity of these symptoms is also dependent on the vessels involved. With regard to the management, is important to note that the vessel ligation with surgery as well as vessel emolization with endovascular procedures have been shown to be effective in the treatment of these cases. In view of that, the present study describes a case of superficial temporal arteriovenous fistula that arose as a postoperative complication of a bilateral arthroscopic eminoplasty of TMJ. The aim of the present report is to characterize this rare syndrome with the goal of proposing suitable treatments. KEY WORDS: Arteriovenous fistula, arthroscopic surgery, eminoplasty of TMJ, temporal vessels. PMID- 27398190 TI - Covalent Tethering of Fragments For Covalent Probe Discovery. AB - Covalent probes and drugs have found widespread use as research tools and clinical agents. Covalent probes are useful because of their increased intracellular potency and because covalent labeling of cellular proteins can be tracked using click chemistry. Covalent drugs, on the other hand, can overcome drug resistance toward their reversible counterparts. The discovery of covalent probes and drugs usually follows two trajectories: covalent natural products and their analogues are used directly as covalent probes or drugs; or alternatively, a non-covalent probe is equipped with a reactive group and converted into a covalent probe. In both cases, there is a need to either have a natural product or a potent non-covalent scaffold. The alternative approach to discover covalent probes is to start with a drug-like fragment that already has an electrophile, and then grow the fragment into a potent lead compound. In this approach, the electrophilic fragment will react covalently with the target protein, and therefore the initial weak binding of the fragment can be amplified over time and detected using mass spectrometry. With this approach the surface of the protein can be interrogated with a library of covalent fragments to identify covalent drug binding sites. One challenge with this approach is the danger of non specific covalent labeling of proteins with covalent fragments. The second challenge is the risk of selecting the most reactive fragment rather than the best binder if the covalent fragments are screened in mixtures. This review will highlight how covalent tethering was developed, its current state, and its future. PMID- 27398191 TI - Leaf lifespan is positively correlated with periods of leaf production and reproduction in 49 herb and shrub species. AB - Leaf life span and plant phenology are central elements in strategies for plant carbon gain and nutrient conservation. Although few studies have found that leaf life span correlate with the patterns of leaf dynamics and reproductive output, but there have not been sufficient conclusive tests for relationships between leaf life span and plant phenological traits, the forms and strengths of such relationships are poorly understood. This study was conducted with 49 herb and shrub species collected from the eastern portion of the Tibetan Plateau and grown together in a common garden setting. We investigated leaf life span, the periods of leaf production and death, the time lag between leaf production and death, and the period of plant reproduction (i.e., flowering and fruiting). Interspecific relationships of leaf life span with leaf dynamics and reproduction period were determined. Leaf production period was far longer than leaf death period and largely reflected the interspecific variation of leaf life span. Moreover, leaf life span was positively correlated with the length of reproduction (i.e., flowering and fruiting) period. These relationships were generally consistent across different subgroups of species (herbs vs. shrubs) and indicate potentially widely applicable relationships between LLS and aboveground phenology. We concluded that leaf life span is associated not simply with the dynamics of the leaf itself but with reproduction period. The results demonstrate a plant trade off in resource allocation between production and reproduction and a coordinated arrangement of leaves, flowers, and fruits in their time investment. Our results provide insight into the relationship between leaf life span and plant phenology. PMID- 27398192 TI - Placenta accreta following hysteroscopic myomectomy. AB - Hardly any report exists on the influence of hysteroscopic myomectomy on subsequent pregnancy. Placenta accreta is most often associated with placenta previa in women with multiple prior cesarean sections. We report the first case of placenta accreta without placenta previa during the first pregnancy subsequent to hysteroscopic myomectomy. PMID- 27398193 TI - Capecitabine-related liver lesions: sinusoidal dilatation mimicking liver metastasis. AB - A 30-year-old lady treated with capecitabine for primary colon adenocarcinoma developed liver lesions suspicious for metastasis. Liver biopsies showed sinusoidal dilatation thought to be secondary to capecitabine. This case highlights the importance of differentiating between benign and malignant liver lesions during cancer surveillance preventing unnecessary liver resections for benign disease. PMID- 27398194 TI - Colon cancer metastasis to the thyroid gland: report of a case with unique molecular profile. AB - A high index of suspicion is needed when a patient presents with thyroid mass in the settings of an advanced CRC. Secondary thyroid malignancy should be considered unless proven otherwise. reatment should be determined considering extent of CRC metastasis, patient's general condition, and presence of local symptoms. PMID- 27398195 TI - Right ventricular thrombus formation in a patient with arrhythmogenic right ventricular dysplasia following radiofrequency ablation. AB - A middle-aged female suffering from ARVD presented for routine follow-up 8 weeks after right ventricular radiofrequency ablation of recurring ventricular tachycardia. Echocardiography revealed two right ventricular thrombi in the scar area of right ventricular radiofrequency ablation. Ablation-related thromboembolic events should be considered as possible complication in patients suffering from ARVD. PMID- 27398196 TI - Wellens' Syndrome with a proximal left anterior descending artery occlusion. AB - The case is a 52-year-old male admitted to cardiology department with chest tightness. Admission ECG showed nontypical T-wave changes in V2-V4 leads in pain peroids, and increasing severe narrowing of proximal LAD. Cardiac enzymes were abnormal. Emergency coronary angiography showed severe stenosis (99%) in proximal LAD. PMID- 27398197 TI - Benign pneumoperitoneum in newborns: which abdomen to open and which one to observe? AB - Benign pneumoperitoneum in newborns is not a rare condition that should be managed conservatively. Neonatologists and surgical teams should work together to avoid unnecessary and potentially risky procedures. PMID- 27398198 TI - Phacomatosis pigmentokeratotica or the Schimmelpenning-Feuerstein-Mims syndrome? AB - Cutaneous symptoms in some patients with clinical picture of Schimmelpenning Feuerstein-Mims syndrome can include a speckled lentiginous nevus, also known as nevus spilus. Recent investigations show that somatic heterozygous HRAS mutations are present in the sebaceous and speckled lentiginous nevus tissues of patients with combination of two nevi. PMID- 27398199 TI - Multiple nodules on the left cheek represented pseudolymphomatous folliculitis. AB - Pseudolymphomatous folliculitis (PLF) is a rare lesion. Sometimes, the clinical appearance is characterized by multiple large, firm violaceous nodules. In cases with multiple lesions, such biopsy should be performed on one lesion, and once PLF is determined, monitoring for the remained tumor is considered to be the best treatment. PMID- 27398200 TI - Kill two birds with one stone: curing accessory pathways and premature ventricular contractions with one ablation. AB - Radiofrequency catheter ablation has been used for treating cardiac arrhythmias, such as premature ventricular contractions and accessory pathway. We report two cases with successful ablation of left-sided accessory pathways and premature ventricular contractions from mitral annulus with one ablation. To our knowledge, no similar reports have been found so far. PMID- 27398201 TI - Post-MI free wall rupture syndrome. Case report, literature review, and new terminology. AB - Common clinical features of subacute rupture left ventricular free wall after acute ST segment elevation myocardial infarction are: (1) recurrent or persistent chest pain; (2) recurrent or persistent ST segment elevation; (3) hypotension. Integrating these signs into a syndrome can increase the clinician's awareness to the fatal complication. PMID- 27398202 TI - Scrub typhus infection in pregnancy: the dilemma of diagnosis and treatment in a resource-limited setting. AB - To save the life of both mother and fetus, the risks and benefits of the few antibiotics considered effective in the treatment of severe scrub typhus require consideration. In this case, chloramphenicol treatment averted maternal but not fetal mortality. Evidence-based guidelines appropriate for resource-limited endemic areas are required. PMID- 27398203 TI - Rapidly progressed aortic stenosis in a patient with previous diagnosis of polycythemia vera and post-polycythemia vera myelofibrosis. AB - Polycythemia vera (PV) is a chronic myeloproliferative disease that is often complicated with thromboembolism. However, aortic stenosis (AS) could be a manifestation of the cardiovascular complications of PV possibly through shear stress and atherosclerosis. We report a rare case of rapidly progressed AS in a patient with PV. PMID- 27398204 TI - DOCK8 deficiency in six Iranian patients. AB - DOCK8 deficiency is a rare autosomal recessive combined immunodeficiency with high IgE level, eosinophilia, severe eczema, extensive cutaneous viral, and respiratory bacterial infections, mostly in populations with higher prevalence of consanguinity. Molecular diagnosis of this gene is a useful approach for early diagnosis and timely HSCT due to deleterious consequences. PMID- 27398205 TI - Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review. AB - Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis. PMID- 27398206 TI - Spontaneous reduction of an incarcerated gravid uterus in the third trimester. AB - An incarcerated gravid uterus is an uncommon complication of pregnancy. On rare occasions, an incarcerated gravid uterus resolves spontaneously even in the third trimester of pregnancy. Severe abdominal pain might be caused by spontaneous reduction and should be considered as a possible cause. PMID- 27398207 TI - Tribal treatment approach to abdominal pain in the Sub-Saharan Tropical Africa. AB - There are different primitive tribal treatment ways in the Sub-Saharan Africa. WHO must try more to educate these communities to abandon such harmful treatment ways. PMID- 27398208 TI - Langer's axillary arch. AB - Langer's axillary arch is usually asymptomatic and difficult to detect preoperatively. When present, it is important for surgeons operating in the axillary region, to identify correctly the relevant anatomy. Simple surgical division is curative and necessary in order to achieve exposure of the axillary contents, lymphatic dissection, and neurovascular preservation. PMID- 27398209 TI - A severe case of hidradenitis suppurativa. AB - Hidradenitis suppurativa (HS) is a chronic disfiguring skin disease affecting apocrine sweat glands, characterized by abscesses, cysts, or infections. There is currently no cure or a consistently effective treatment. HS is a challenging condition to diagnose and treat. We present a severe case to raise awareness of this disabling condition. PMID- 27398210 TI - Colonic stenting in malignant large bowel obstruction. AB - In patients who are surgical candidates, colonic stenting is beneficial for preoperative decompression in large bowel obstruction, as it can convert a surgical procedure from an emergent two-step approach into an elective one-step resection with a primary anastomosis. PMID- 27398211 TI - Patterned charring along the contact points of a metallic locket due to lightning strike. AB - Superficial cutaneous burns following lightning strike may vary in patterns ranging from linear burns, punctate burns, feathering burns, and thermal burns. Contact with an extrinsic object in the pathway of lightning current can lead to disastrous consequences. The lucky who survive may show bizarre and interesting burn patterns to tell their story. PMID- 27398212 TI - Giant splenic artery aneurysm rupture. AB - Little exists on treatment for SAAs rupture which may require a fast bleeding control because of the hemodynamic instability and a large perisplenic/peritoneal hematoma. This case shows the use of endovascular clamping and midline laparotomy to perform the splenectomy because of the severe hypotension and the dimension of the lesion. PMID- 27398213 TI - Corrigendum. AB - [This corrects the article DOI: 10.1002/ccr3.389.]. PMID- 27398214 TI - Photo-active collagen systems with controlled triple helix architecture. AB - The design of photo-active collagen systems is presented as a basis for establishing biomimetic materials with varied network architecture and programmable macroscopic properties. Following in-house isolation of type I collagen, reaction with vinyl-bearing compounds of varied backbone rigidity, i.e. 4-vinylbenzyl chloride (4VBC) and glycidyl methacrylate (GMA), was carried out. TNBS colorimetric assay, 1H-NMR and ATR-FTIR confirmed covalent and tunable functionalization of collagen lysines. Depending on the type and extent of functionalization, controlled stability and thermal denaturation of triple helices were observed via circular dichroism (CD), whereby the hydrogen-bonding capability of introduced moieties was shown to play a major role. Full gel formation was observed following photo-activation of functionalized collagen solutions. The presence of a covalent network only slightly affected collagen triple helix conformation (as observed by WAXS and ATR-FTIR), confirming the structural organization of functionalized collagen precursors. Photo-activated hydrogels demonstrated an increased denaturation temperature (DSC) with respect to native collagen, suggesting that the formation of the covalent network successfully stabilized collagen triple helices. Moreover, biocompatibility and mechanical competence of obtained hydrogels were successfully demonstrated under physiologically-relevant conditions. These results demonstrate that this novel synthetic approach enabled the formation of biocompatible collagen systems with defined network architecture and programmable macroscopic properties, which can only partially be obtained with current synthetic methods. PMID- 27398215 TI - Near-infrared luminescent CaTiO3:Nd3+ nanofibers with tunable and trackable drug release kinetics. AB - 750-850 nm (NIR I) and 1000-1400 nm (NIR II) in the near infrared (NIR) spectra are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. Monitoring drug release from the drug carrier is still a daunting challenge in the field of nanomedicine. To overcome such a challenge, we propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR I to emit NIR II light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR II emission intensity. Towards this end, we first used electrospinning to prepare porous Nd3+ doped CaTiO3 nanofibers by adding micelle-forming surfactant Pluronic F127, followed by annealing to remove the organic component. After a model drug, ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline (PBS) solution was monitored by detecting the NIR II emission from the nanofibers. We found that the release of the drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR II emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR II emission, allowing us to monitor the drug release by simply detecting the intensity of NIR II from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming surfactant Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+ doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission. PMID- 27398216 TI - Solubilised bright blue-emitting iridium complexes for solution processed OLEDs. AB - Combining a sterically bulky, electron-deficient 2-(2,4-difluorophenyl)-4-(2,4,6 trimethylphenyl)pyridine (dFMesppy) cyclometalating C?N ligand with an electron rich, highly rigidified 1,1'-(alpha,alpha'-o-xylylene)-2,2'-biimidazole (o xylbiim) N?N ligand gives an iridium complex, [Ir(dFMesppy)2(o-xylbiim)](PF6), that achieves extraordinarily bright blue emission (PhiPL = 90%; lambdamax = 459 nm in MeCN) for a cationic iridium complex. This complex is compared with two reference complexes bearing 4,4'-di-tert-butyl-2,2'-bipyridine, and solution processed organic light emitting diodes (OLEDs) have been fabricated from these materials. PMID- 27398217 TI - Is intracouple assisted reproductive technology an option for men with large headed spermatozoa? A literature review and a decision guide proposal. AB - Although the presence of spermatozoa with an abnormally large head is rare, it is associated with low fertility or even total infertility. We reviewed the literature on assisted reproductive technology (ART) strategies and outcomes for men with large-headed spermatozoa. We also discuss additional analyses that can usefully characterize sperm defects and help with the choice between intra-couple ART and insemination with donor sperm. Lastly, we propose a classification for cases of large-headed spermatozoa. PMID- 27398219 TI - IgG4-related hypophysitis presenting as diabetes insipidus with tubulo interstital nephritis and mediastinal lymphadenopathy. AB - IgG4-related disease (IgG4-RD) is a rare but increasingly recognised condition, emerging as a clinical entity following the observation of the associations of autoimmune pancreatitis. IgG4-RD is characterised by extensive infiltration of IgG4-positive plasma cells into multiple organs and raised serum IgG4 levels. Clinical manifestations of IgG4 disease classically include autoimmune pancreatitis, lacrimal or salivary gland infiltration (formerly known as Mikulicz disease) and retroperitoneal fibrosis. More rarely, IgG4 disease can cause pituitary hypophysitis. Although most frequently described in middle-aged males, the epidemiology and pathogenesis of the disease remain largely undefined. Nevertheless, an understanding of the wide variety of clinical manifestations of this multi-system condition is undeniably important given the often excellent outcomes following treatment. We describe an unusual presentation of IgG4 disease with isolated diabetes insipidus secondary to pituitary hypophysitis. The patient in question subsequently developed chest pain secondary to mediastinal lymphadenopathy and tubulo-interstitial nephritis leading to renal dysfunction. He was successfully treated with oral steroids and had regular follow-up, and remains well at follow-up 2 years later. LEARNING POINTS: IgG4 disease, although rare, is increasing in prevalence largely due to increased recognition of its clinical manifestations, including autoimmune pancreatitis, lacrimal or salivary gland infiltration, retroperitoneal fibrosis and, more rarely, lymphocytic hypophysitis presenting as diabetes insipidus.IgG4 disease is highly treatable, and symptoms may show complete resolution with administration of steroids, highlighting the importance of correct and timely diagnosis.Causes of lymphocytic hypophysitis are varied and not distinguishable radiologically. Given the difficulty in biopsying the pituitary, careful attention must be paid to the systemic clinical presentation to provide clues as to the underlying disorder. PMID- 27398218 TI - Nanogels as imaging agents for modalities spanning the electromagnetic spectrum. AB - In the past few decades, advances in imaging equipment and protocols have expanded the role of imaging in in vivo diagnosis and disease management, especially in cancer. Traditional imaging agents have rapid clearance and low specificity for disease detection. To improve accuracy in disease identification, localization and assessment, novel nanomaterials are frequently explored as imaging agents to achieve high detection specificity and sensitivity. A promising material for this purpose are hydrogel nanoparticles, whose high hydrophilicity, biocompatibility, and tunable size in the nanometer range make them ideal for imaging. These nanogels (10 to 200 nm) can circumvent uptake by the reticuloendothelial system, allowing longer circulation times than small molecules. In addition, their size/surface properties can be further tailored to optimize their pharmacokinetics for imaging of a particular disease. Herein, we provide a comprehensive review of nanogels as imaging agents in various modalities with sources of signal spanning the electromagnetic spectrum, including MRI, NIR, UV-vis, and PET. Many materials and formulation methods will be reviewed to highlight the versatility of nanogels as imaging agents. PMID- 27398220 TI - Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone induced thyrotoxicosis. AB - Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy. LEARNING POINTS: Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery. PMID- 27398221 TI - A large deletion in RPGR causes XLPRA in Weimaraner dogs. AB - BACKGROUND: Progressive retinal atrophy (PRA) belongs to a group of inherited retinal disorders associated with gradual vision impairment due to degeneration of retinal photoreceptors in various dog breeds. PRA is highly heterogeneous, with autosomal dominant, recessive or X-linked modes of inheritance. In this study we used exome sequencing to investigate the molecular genetic basis of a new type of PRA, which occurred spontaneously in a litter of German short-hair Weimaraner dogs. RESULTS: Whole exome sequencing in two PRA-affected Weimaraner dogs identified a large deletion comprising the first four exons of the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene known to be involved in human retinitis pigmentosa and canine PRA. Screening of 16 individuals in the corresponding pedigree of short-hair Weimaraners by qPCR, verified the deletion in hemizygous or heterozygous state in one male and six female dogs, respectively. The mutation was absent in 88 additional unrelated Weimaraners. The deletion was not detectable in the parents of one older female which transmitted the mutation to her offspring, indicating that the RPGR deletion represents a de novo mutation concerning only recent generations of the Weimaraner breed in Germany. CONCLUSION: Our results demonstrate the value of an existing DNA biobank combined with exome sequencing to identify the underlying genetic cause of a spontaneously occurring inherited disease. Identification of the genetic cause has allowed the development of a diagnostic test, which should help to eradicate the PRA causing mutation from the respective canine line. Thus, planning of future pairings is facilitated and manifestation of this type of PRA can be prevented. PMID- 27398222 TI - Correlation of adiposity indices with cardiovascular disease risk factors in healthy adults of Singapore: a cross-sectional study. AB - BACKGROUND: Obesity has long been highlighted for its association with increased incidence of cardiovascular disease (CVD). Nonetheless, the best adiposity indices to evaluate the CVD risk factors remain contentious and few studies have been performed in Asian populations. In the present study, we compared the association strength of percent body fat (PBF) to indirect anthropometric measures of general adiposity (body mass index (BMI) and body adiposity index (BAI)) and central adiposity (waist circumference (WC), and waist-to-hip ratio (WHR)) for the prediction of CVD risk factors in healthy men and women living in Singapore. METHODS: A total of 125 individuals (63 men and 62 women) took part in this study. PBF was measured by using three different techniques, including bioelectrical impedance analysis (BIA), BOD POD, and dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements (WC, hip circumference (HC), height, and weight), fasting blood glucose (FBG), fasting serum insulin (FSI), and lipid profiles were determined according to standard protocols. Correlations of anthropometric measurements and PBF with CVD risk factors were compared. RESULTS: Irrespective of the measuring techniques, PBF showed strong positive correlations with FSI, HOMA-IR, TC/HDL, TG/HDL, and LDL/HDL in both genders. While PBF was highly correlated with FBG, SBP, and DBP in females, no significant relationships were observed in males. Amongst the five anthropometric measures of adiposity, BAI was the best predictor for CVD risk factors in female participants (r = 0.593 for HOMA-IR, r = 0.542 for TG/HDL, r = 0.474 for SBP, and r = 0.448 for DBP). For males, the combination of WC (r = 0.629 for HOMA-IR, and r = 0.446 for TG/HDL) and WHR (r = 0.352 for SBP, and r = 0.366 for DBP) had the best correlation with CVD risk factors. CONCLUSION: Measurement of PBF does not outperform the simple anthropometric measurements of obesity, i.e. BAI, WC, and WHR, in the prediction of CVD risk factors in healthy Asian adults. While measures of central adiposity (WC and WHR) tend to show stronger associations with CVD risk factors in males, measures of general adiposity (BAI) seems to be the best predictor in females. The gender differences in the association between adiposity indices and CVD risk factors may relate to different body fat distribution in males and females living in Singapore. These results may find further clinical utility to identify patients with CVD risk factors in a more efficient way. PMID- 27398223 TI - Vitamin D status in cats with feline immunodeficiency virus. AB - Feline immunodeficiency virus (FIV) is a lentivirus that can lead to a syndrome of acquired immune dysfunction. Infected cats often remain asymptomatic for several years before immune dysfunction leads to an increased risk for the development of systemic diseases, neoplasia and opportunistic infections. FIV is structurally related to human immunodeficiency virus (HIV) and the pathogenesis of FIV-related disease is similar to that seen in HIV-infected patients. Observational studies have documented an association between low plasma vitamin D and HIV infection. Vitamin D status has been shown to be associated with HIV related disease progression, morbidity and mortality. The objective of this study was to examine the hypothesis that vitamin D status, as assessed by serum 25 hydroxyvitamin D [25(OH)D] concentrations, are lower in cats with FIV infection compared to healthy control cats. Serum 25(OH)D concentrations were measured in 20 healthy cats, 39 hospitalized ill cats and 59 cats infected with FIV. Cats which were FIV infected had significantly lower 25(OH)D concentrations compared to healthy control cats. Serum 25(OH)D concentrations were not significantly different between FIV-infected cats and hospitalized ill cats. Further investigations are warranted to determine whether vitamin D status influences the prognosis of cats infected with FIV. PMID- 27398224 TI - Cesarean section in sub-Saharan Africa. AB - Cesarean section is an essential maternal healthcare service. Its role in labor and delivery care in low- and middle-income countries is complex; in many low resource settings it is underutilized in the most needy of populations and overused by the less needy, without clear methods to ensure that universal access is available. Additionally, even if universal access were available, it is not evident that these countries would have the capacity or the finances to appropriate meet demand for the procedure, or that patients would want to utilize the care. This review summarizes the literature and illustrates the complicated relationship that cesarean section, which is rapidly on the rise around the world, has with individuals, communities, and nations in sub-Saharan Africa. PMID- 27398225 TI - Elevated prothrombin time/international normalized ratio associated with concurrent administration of regorafenib and warfarin in a patient with advanced colorectal cancer. AB - BACKGROUND: Regorafenib and its metabolites may inhibit the activities of several CYP or UDP-glucuronosyltransferase isoforms, including that of CYP2C9. Therefore, pharmacological agents that are CYP2C9 substrates may show elevated circulating levels and enhanced drug efficacy when concurrently used with regorafenib. Previous studies showed that the area under the plasma concentration-time curve of warfarin, which is the substrate for CYP2C9, increased upon co-administration of regorafenib. However, there are no reports indicating that the anticoagulant effects of warfarin increased upon co-administration of regorafenib. CASE PRESENTATION: We report a case of a 76-year-old man with liver metastasis of colon cancer. He was treated with regorafenib at a dosage of 120 mg daily on days 1 to 21 every 4 weeks as a third-line therapy. He had a history of acute myocardial infarction and had taken 2 mg warfarin daily. Three weeks after the treatment began, PT/INR values markedly increased, although there was no hemorrhage. Administration of regorafenib and warfarin was discontinued, and then PT/INR rapidly decreased. Warfarin administration was restarted (0.5 mg daily) and the dose was increased up to 1.5 mg daily. The patient's PT/INR values exhibited a tendency to increase when concurrently used with regorafenib, the dose of which was reduced to 80 mg daily on days 1 to 14 every 3 weeks at a physician's discretion. CONCLUSIONS: The clinical course of this patient suggested that PT/INR might increase during concurrent use of warfarin and regorafenib. Therefore, PT/INR should be periodically monitored during the concurrent use of warfarin and regorafenib. PMID- 27398226 TI - Chronic hypoxia down-regulates tight junction protein ZO-2 expression in children with cyanotic congenital heart defect. AB - AIMS: Tight junction protein zonula occludens protein 2 (ZO-2) is a member of the membrane-associated guanylate kinases protein family known to be expressed at tight junctions of epithelial and endothelial cells and at adherens junctions (AJs) in cardiomyocytes. Little is known about ZO-2 expression and function in the human heart. Here, we examined the hypothesis that chronic hypoxia down regulates ZO-2 expression in human myocardium and cultured rat cardiomyocytes. METHODS AND RESULTS: Patients with a diagnosis of cyanotic (n = 10) or acyanotic (n = 10) Tetralogy of Fallot undergoing surgical repair were used to examine ZO-2 messenger RNA and protein expression by real time-PCR, immunohistochemistry, and western blotting. A model of cultured rat cardiomyocytes was used to measure ZO-2 and AJ proteins levels in response to hypoxia and to investigate ZO-2 cellular localization. We showed that ZO-2 is expressed in myocardial tissue in acyanotic and cyanotic children with congenital heart defects. ZO-2 was specifically down regulated in cyanotic myocardium at both the messenger RNA and protein levels when compared with acyanotic patients. This specific down-regulation can be mimicked in cultured rat cardiomyocytes by treating them with hypoxic conditions confirming that ZO-2 gene down-regulation is specifically due to cyanosis. Furthermore, in addition to its cytoplasmic expression, ZO-2 showed nuclear expression in cultured rat cardiomyocytes suggesting potential role in transcription regulation. CONCLUSIONS: Hypoxia down-regulates ZO-2 expression in both cyanotic patient's myocardium and cultured rat cardiomyocytes. This down regulation suggest an involvement of ZO-2 in cardiac remodelling of AJs in cyanotic children and may explain the greater susceptibility of cyanotic patients to corrective heart surgery. PMID- 27398227 TI - Lead toxicity and genetics in Flint, MI. PMID- 27398228 TI - The evolving role of bariatric surgery in patients with type 1 diabetes and obesity. AB - Bariatric surgery has emerged as a viable treatment option in morbidly obese individuals with type 2 diabetes. Concomitant with societal lifestyle changes and the increased emphasis on achieving metabolic targets, there has been a rise in the number of patients with type 1 diabetes (T1DM) who are overweight and obese. Preliminary experience based on a limited number of observational reports points to substantial weight loss and amelioration of comorbid conditions such as blood pressure and dyslipidemia in patients with T1DM who undergo weight loss surgery. However, there is little evidence to suggest significant improvement in glycemic control and lowering of glycosylated hemoglobin, and bariatric surgical procedures do not necessarily lead to enhanced diabetes management. and improved quality of life. The potential possibility of micronutrient deficiency, weight regain, and psychobehavioral issues post-bariatric surgery also exists. An individualized evaluation of the risks and benefits should be considered, using a a multidisciplinary team approach with expertise in patient selection, surgical technique, and follow-up. A crucial component is the availability of a diabetes care specialist or endocrinologist experienced in intensive, tailored, modifiable insulin regimens who maintains close and careful monitoring during all phases of management. Reliable data from a prospective, longitudinal perspective is required to provide guidelines for clinicians and informed choices for obese patients with T1DM who are contemplating bariatric surgery. PMID- 27398229 TI - Persister formation in Staphylococcus aureus is associated with ATP depletion. AB - Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic infections and antibiotic treatment failure1-3. In Escherichia coli, toxin/antitoxin (TA) modules have been linked to persister formation4-6. The mechanism of persister formation in Gram-positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrance into stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers is associated with a 100-1000 fold increase in the likelihood of survival to antibiotic challenge. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotics. PMID- 27398231 TI - A multistep continuous flow synthesis machine for the preparation of pyrazoles via a metal-free amine-redox process. AB - A versatile multistep continuous flow setup is reported for the four-step conversion of anilines into pyrazole products. The synthesis machine incorporates the use of amine-redox chemistry through diazotization and a metal-free vitamin C mediated reduction. The machine can be used for the synthesis of an array of analogues or the scale up of an individual target. PMID- 27398232 TI - Improving documentation of clinical care within a clinical information network: an essential initial step in efforts to understand and improve care in Kenyan hospitals. AB - In many low income countries health information systems are poorly equipped to provide detailed information on hospital care and outcomes. Information is thus rarely used to support practice improvement. We describe efforts to tackle this challenge and to foster learning concerning collection and use of information. This could improve hospital services in Kenya. We are developing a Clinical Information Network, a collaboration spanning 14 hospitals, policy makers and researchers with the goal of improving information available on the quality of inpatient paediatric care across common childhood illnesses in Kenya. Standardised data from hospitals' paediatric wards are collected using non commercial and open source tools. We have implemented procedures for promoting data quality which are performed prior to a process of semi-automated analysis and routine report generation for hospitals in the network. In the first phase of the Clinical Information Network, we collected data on over 65 000 admission episodes. Despite clinicians' initial unfamiliarity with routine performance reporting, we found that, as an initial focus, both engaging with each hospital and providing them information helped improve the quality of data and therefore reports. The process has involved mutual learning and building of trust in the data and should provide the basis for collaborative efforts to improve care, to understand patient outcome, and to evaluate interventions through shared learning. We have found that hospitals are willing to support the development of a clinically focused but geographically dispersed Clinical Information Network in a low-income setting. Such networks show considerable promise as platforms for collaborative efforts to improve care, to provide better information for decision making, and to enable locally relevant research. PMID- 27398235 TI - Structural Modeling and Analysis of Pregnancy-Associated Glycoprotein-1 of Buffalo (Bubalus bubalis). AB - The present study was conducted to design and analyze the structural model of buffalo pregnancy-associated glycoprotein-1 (PAG-1) using bioinformatics. Structural modeling of the deduced buffalo PAG-1 protein was done using PHYRE, CONSURF servers and its structure was subsequently constructed using MODELLER 9.9 and PyMOL softwares Buffalo PAG-1 structural conformity was analyzed using PROSA, WHATIF, and 3D-PSSM servers. Designed buffalo PAG-1 protein structure on BLAST analysis retrieved protein structures belonging to aspartic proteinase family. Moreover in silico analysis revealed buffalo PAG-1 protein retained bilobed structure with pepstatin-binding clefts near the active sites by docking studies with pepstatin A using PatchDock server. Structural studies revealed that the amino and carboxy terminal containing aspartic residues are highly conserved and buried within the protein structure. Structural conformity studies showed that more than 90% of the residues lie inside favored and allowed regions. It was also deduced that buffalo PAG-1 possesses low and high energy zones with a very low threshold for proteolysis ascertaining the stableness of the buffalo PAG-1 protein structure. This study depicts the structural conformity and stability of buffalo PAG-1 protein. PMID- 27398234 TI - Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair. AB - Faithful transmission of genetic information through generations ensures genomic stability and integrity. However, genetic alterations occur every now and then during the course of genome duplication. In order to repair these genetic defects and lesions, nature has devised several repair pathways which function promptly to prevent the cell from accumulating permanent mutations. These repair mechanisms seem to be significantly impacted by posttranslational modifications of proteins like phosphorylation and ubiquitination. Protein ubiquitination is emerging as a critical regulatory mechanism of DNA damage response. Non proteolytic, proteasome-independent functions of ubiquitin involving monoubiquitination and polyubiquitination of DNA repair proteins contribute significantly to the signaling of DNA repair pathways. In this paper, we will particularly highlight the work on ubiquitin-mediated signaling in the repair processes involving the Fanconi anemia pathway, translesional synthesis, nucleotide excision repair, and repair of double-strand breaks. We will also discuss the role of ubiquitin ligases in regulating checkpoint mechanisms, the role of deubiquitinating enzymes, and the growing possibilities of therapeutic intervention in this ubiquitin-conjugation system. PMID- 27398236 TI - Nucleotide Sequencing and SNP Detection of Toll-Like Receptor-4 Gene in Murrah Buffalo (Bubalus bubalis). AB - Toll-like receptor-4 (TLR-4) has an important pattern recognition receptor that recognizes endotoxins associated with gram negative bacterial infections. The present investigation was carried out to study nucleotide sequencing and SNP detection by PCR-RFLP analysis of the TLR-4 gene in Murrah buffalo. Genomic DNA was isolated from 102 lactating Murrah buffalo from NDRI herd. The amplified PCR fragments of TLR-4 comprised of exon 1, exon 2, exon 3.1, and exon 3.2 were examined to RFLP. PCR products were obtained with sizes of 165, 300, 478, and 409 bp. TLR-4 gene of investigated Murrah buffaloes was highly polymorphic with AA, AB, and BB genotypes as revealed by PCR-RFLP analysis using Dra I, Hae III, and Hinf I REs. Nucleotide sequencing of the amplified fragment of TLR-4 gene of Murrah buffalo was done. Twelve SNPs were identified. Six SNPs were nonsynonymous resulting in change in amino acids. Murrah is an indigenous Buffalo breed and the presence of the nonsynonymous SNP is indicative of its unique genomic architecture. Sequence alignment and homology across species using BLAST analysis revealed 97%, 97%, 99%, 98%, and 80% sequence homology with Bos taurus, Bos indicus, Ovis aries, Capra hircus, and Homo sapiens, respectively. PMID- 27398237 TI - Increased Phospho-Keratin 8 Isoforms in Colorectal Tumors Associated with EGFR Pathway Activation and Reduced Apoptosis. AB - Hyperphosphorylated keratin (K) 8 acts as a phosphate "sponge" for stress activated protein kinases thereby inhibiting pro-apoptotic molecules and thus apoptosis. MAP kinase/ERK1 has increased activity in colorectal cancer (CRC) and is known to phosphorylate K8. The aims were to identify the K8 isoforms abundantly present in colon tumors, using 2D difference gel electrophoresis (DIGE), to identify the modifications using mass spectrometry, and to validate the differential abundance of these isoforms in tumors relative to matched normal mucosae. 2D DIGE showed 3 isoforms of K8 significantly increased in tumor >=2 fold in 6/8 pairs. Metal oxide affinity chromatography mass spectrometry and bioinformatics were used to identify phosphorylated serine residues. Levels of PS24, PS432, and PS74 by western blotting were found to be significantly increased in tumor versus matched normal. Blocking of EGFR signaling in Caco2 cells showed a significant decrease (P < 0.0001) in K8 PS74 and PS432 levels by 59% and 66%, respectively, resulting in increased apoptosis. PMID- 27398238 TI - Functional Characterization of a Small-Molecule Inhibitor of the DKK1-LRP6 Interaction. AB - Background. DKK1 antagonizes canonical Wnt signalling through high-affinity binding to LRP5/6, an essential component of the Wnt receptor complex responsible for mediating downstream canonical Wnt signalling. DKK1 overexpression is known for its pathological implications in osteoporosis, cancer, and neurodegeneration, suggesting the interaction with LRP5/6 as a potential therapeutic target. Results. We show that the small-molecule NCI8642 can efficiently displace DKK1 from LRP6 and block DKK1 inhibitory activity on canonical Wnt signalling, as shown in binding and cellular assays, respectively. We further characterize NCI8642 binding activity on LRP6 by Surface Plasmon Resonance (SPR) technology. Conclusions. This study demonstrates that the DKK1-LRP6 interaction can be the target of small molecules and unlocks the possibility of new therapeutic tools for diseases associated with DKK1 dysregulation. PMID- 27398239 TI - K-Ras Mutations in Non-Small-Cell Lung Cancer: Prognostic and Predictive Value. AB - Non-small-cell lung cancer (NSCLC) is a heterogeneous disease due to the presence of different clinically relevant molecular subtypes. Until today, several biological events have been identified in lung adenocarcinoma, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, offering new hopes to patients with metastatic disease. Unfortunately, in approximately 50% of adenocarcinoma and for those harbouring K RAS mutations, the most frequent mutation in Caucasian lung adenocarcinoma, so far no specific drug demonstrated efficacy. The rat sarcoma (RAS) genes, including H-RAS, K-RAS, and N-RAS, encode a family of proteins regulating cell growth, differentiation, and apoptosis. K-RAS mutations are present in 20-30% of NSCLC and occur most commonly, but not exclusively, in adenocarcinoma histology and life-long smokers. Although in colorectal cancer patients K-RAS mutations represent a validated negative predictive biomarker for treatment with anti-EGFR monoclonal antibodies, their role in selecting specific treatment for NSCLC patients remains undefined. Aim of the present paper is to critically analyze the prognostic and predictive value of K-RAS mutations in NSCLC. PMID- 27398241 TI - Characterization of Histone H2A Derived Antimicrobial Peptides, Harriottins, from Sicklefin Chimaera Neoharriotta pinnata (Schnakenbeck, 1931) and Its Evolutionary Divergence with respect to CO1 and Histone H2A. AB - Antimicrobial peptides (AMPs) are humoral innate immune components of fishes that provide protection against pathogenic infections. Histone derived antimicrobial peptides are reported to actively participate in the immune defenses of fishes. Present study deals with identification of putative antimicrobial sequences from the histone H2A of sicklefin chimaera, Neoharriotta pinnata. A 52 amino acid residue termed Harriottin-1, a 40 amino acid Harriottin-2, and a 21 mer Harriottin-3 were identified to possess antimicrobial sequence motif. Physicochemical properties and molecular structure of Harriottins are in agreement with the characteristic features of antimicrobial peptides, indicating its potential role in innate immunity of sicklefin chimaera. The histone H2A sequence of sicklefin chimera was found to differ from previously reported histone H2A sequences. Phylogenetic analysis based on histone H2A and cytochrome oxidase subunit-1 (CO1) gene revealed N. pinnata to occupy an intermediate position with respect to invertebrates and vertebrates. PMID- 27398240 TI - Ion Transporters and Abiotic Stress Tolerance in Plants. AB - Adaptation of plants to salt stress requires cellular ion homeostasis involving net intracellular Na(+) and Cl(-) uptake and subsequent vacuolar compartmentalization without toxic ion accumulation in the cytosol. Sodium ions can enter the cell through several low- and high-affinity K(+) carriers. Some members of the HKT family function as sodium transporter and contribute to Na(+) removal from the ascending xylem sap and recirculation from the leaves to the roots via the phloem vasculature. Na(+) sequestration into the vacuole depends on expression and activity of Na(+)/H(+) antiporter that is driven by electrochemical gradient of protons generated by the vacuolar H(+)-ATPase and the H(+)-pyrophosphatase. Sodium extrusion at the root-soil interface is presumed to be of critical importance for the salt tolerance. Thus, a very rapid efflux of Na(+) from roots must occur to control net rates of influx. The Na(+)/H(+) antiporter SOS1 localized to the plasma membrane is the only Na(+) efflux protein from plants characterized so far. In this paper, we analyze available data related to ion transporters and plant abiotic stress responses in order to enhance our understanding about how salinity and other abiotic stresses affect the most fundamental processes of cellular function which have a substantial impact on plant growth development. PMID- 27398242 TI - Mirror-enhanced super-resolution microscopy. AB - Axial excitation confinement beyond the diffraction limit is crucial to the development of next-generation, super-resolution microscopy. STimulated Emission Depletion (STED) nanoscopy offers lateral super-resolution using a donut-beam depletion, but its axial resolution is still over 500 nm. Total internal reflection fluorescence microscopy is widely used for single-molecule localization, but its ability to detect molecules is limited to within the evanescent field of ~ 100 nm from the cell attachment surface. We find here that the axial thickness of the point spread function (PSF) during confocal excitation can be easily improved to 110 nm by replacing the microscopy slide with a mirror. The interference of the local electromagnetic field confined the confocal PSF to a 110-nm spot axially, which enables axial super-resolution with all laser scanning microscopes. Axial sectioning can be obtained with wavelength modulation or by controlling the spacer between the mirror and the specimen. With no additional complexity, the mirror-assisted excitation confinement enhanced the axial resolution six-fold and the lateral resolution two-fold for STED, which together achieved 19-nm resolution to resolve the inner rim of a nuclear pore complex and to discriminate the contents of 120 nm viral filaments. The ability to increase the lateral resolution and decrease the thickness of an axial section using mirror-enhanced STED without increasing the laser power is of great importance for imaging biological specimens, which cannot tolerate high laser power. PMID- 27398243 TI - What makes the Tc of monolayer FeSe on SrTiO3 so high: a sign-problem-free quantum Monte Carlo study. AB - Monolayer FeSe films grown on SrTiO3 (STO) substrate show superconducting gap opening temperatures ([Formula: see text]) which are almost an order of magnitude higher than those of the bulk FeSe and are highest among all known Fe-based superconductors. Angle-resolved photoemission spectroscopy observed "replica bands" suggesting the importance of the interaction between FeSe electrons and STO phonons. These facts rejuvenated the quest for [Formula: see text] enhancement mechanisms in iron-based, especially iron-chalcogenide, superconductors. Here, we perform the first numerically-exact sign-problem-free quantum Monte Carlo simulations to iron-based superconductors. We (1) study the electronic pairing mechanism intrinsic to heavily electron doped FeSe films, and (2) examine the effects of electron-phonon interaction between FeSe and STO as well as nematic fluctuations on [Formula: see text]. Armed with these results, we return to the question "what makes the [Formula: see text] of monolayer FeSe on SrTiO3 so high?" in the conclusion and discussions. PMID- 27398244 TI - The Wonders of Phosphodiesterase-5 Inhibitors: A Majestic History. AB - The Nobel Prize winning discovery of nitric oxide (NO) in 1986 was the starting point for a new innovation in drug discovery. NO acting as a mediator at different physiological systems is believed to be involved in many physiological and pathological conditions through the formation of the second messenger cyclic guanosine monophosphate (cGMP). cGMP-dependent vasodilation effect of NO is important in regulating pulmonary and systemic pressures, maintaining penis erection, preventing atherosclerosis, preventing platelet aggregation, and protecting and controlling cardiac functions. The main enzyme involved in the termination of cGMP effects is phosphodiesterase enzyme 5 (PDE-5), which is overexpressed in ventricular hypertrophy and heart failure. A milestone in drug discovery was the selective inhibitors of PDE-5 that developed to be a multibillion dollar blockbuster in drug market. PDE-5 inhibitors are approved for the treatment of erectile dysfunctions (EDs), pulmonary hypertension, and benign prostatic hypertrophy. They are also under clinical trials for their cardiac protection against damage induced by ischemia or heart failure. This review article is an update about the pharmacotherapeutics of PDE-5 inhibitors and the majestic history that led to their discovery. The information reported in this review was obtained from the electronic sources of different databases such as PubMed Central, Google Scholar, and Scopus. Keywords used for search included cGMP (mechanisms and functions), EDs (drugs used), nitric oxide, and PDE-5 inhibitors (clinical applications). A total of 165 articles were studied, of which 45 articles were referred to in this review. PMID- 27398245 TI - Ghrelin and its Association with Nutritional and Inflammatory Status of Patients on Maintenance Hemodialysis in a South Indian Tertiary Care Hospital. AB - BACKGROUND: Malnutrition and inflammation are associated with morbidity and mortality in patients on maintenance hemodialysis (MHD). Ghrelin, an orexigenic peptide hormone, is speculated to be associated with nutritional and inflammatory status in MHD. AIM: To assess the serum total ghrelin levels and its possible relationship with inflammation and nutritional status in patients on MHD. SUBJECTS AND METHODS: The study was conducted on 90 patients on MHD for 6 months and above (56 males, 34 females, mean age 52.6 [11.7] years; mean dialysis vintage 20.9 [12.1] months) and 70 healthy volunteers as control (5 males, 25 females, mean age 50.6 [9.7] years). Demographics were obtained for the study population, and dialysis-related data were collected for cases. Anthropometry, biochemical parameters, serum total ghrelin and inflammatory markers tumor necrosis factor-alpha (TNF-alpha), and high-sensitivityC-reactive protein (hsCRP) were assessed for cases and control. Self-reported appetite (five questions of appetite and diet assessment tool) and nutritional status (subjective global assessment-dialysis malnutrition score) were assessed for cases. RESULTS: Ghrelin (242.5 [62.3] pg/mL vs. 80.2 [19.6] pg/mL; P < 0.001), TNF-alpha (39.8 [15.2] pg/mL vs. 6.5 [1.2] pg/mL; P < 0.001), hsCRP (10.2 [2.8] mg/L vs. 2.7 [0.54] mg/L; P < 0.001) were significantly elevated in cases versus control, anthropometry, and biochemical parameters were significantly decreased in hemodialysis patient. Of 90 cases, (13/90 [14.4%]) were well-nourished, (28/90 [31%]) mild to moderately malnourished, and (49/90 [54.4%]) were moderate to severely malnourished. Appetite was very good for14.4%, good and fair for 47.8%, poor and very poor for 37.8% patients. There was a significant difference in appetite with respect to nutritional status (P < 0.001). Ghrelin had positive correlation with inflammatory markers and negative correlation with nutritional status (P < 0.001). CONCLUSION: The study identified the association of ghrelin with appetite, nutritional, and inflammatory status of the patients on MHD. PMID- 27398246 TI - Seroprevalence and Correlates of Hepatitis C Virus Infection in Secondary School Children in Enugu, Nigeria. AB - BACKGROUND: Although children comprise a small fraction of the burden of hepatitis C virus (HCV) infections, which is a major global health challenge, a significant number of them develop chronic HCV infection and are at risk of its complications. AIM: The aim of the current study was to determine the prevalence and associated factors of HCV infection in school children in Enugu urban. SUBJECTS AND METHODS: This was a cross-sectional seroepidemiological study involving children aged 10-18 years selected using multistage systematic sampling in Enugu metropolis, Southeast Nigeria. The anti-HCV was tested using a 3(rd) generation enzyme-linked immunosorbent assay. Data were analyzed using SPSS Version 16.0 with the level of significance set at P < 0.05. RESULTS: Four hundred and twenty children were selected and screened comprising 210 (50.0%) males and females. The seroprevalence of anti-HCV was 4 (1.0%). Three (75%) out of the four positive cases for the anti-HCV were females while one was a male giving a male to female ratio of 0.3-1. Traditional scarifications/tattoos were the putative risk factors observed to be significantly associated with anti-HCV seropositivity. CONCLUSION: This study has demonstrated an anti-HCV seroprevalence of 1.0% among children aged 10-18 years in Enugu with traditional scarification as the predominant associated risk factor. Proper health education including school health education and promotion of behavioral change among the public on the practice of safe scarifications/tattoos should be encouraged in our setting. PMID- 27398247 TI - Emergence of Multidrug Resistance and Metallo-beta-lactamase Producing Acinetobacter baumannii Isolated from Patients in Shiraz, Iran. AB - BACKGROUND: Metallo-beta-lactamase (MbetaL) enzymes production is one of the most important resistance mechanisms against carbapenems in some bacteria including Acinetobacter baumannii. AIMS: This study was aimed to determine the antimicrobial susceptibility and the prevalence of MbetaL among carbapenem resistant isolates of A. baumannii. MATERIALS AND METHODS: In this cross sectional study from October 2012 to April 2013, 98 isolates were identified as A. baumannii using MicrogenTM kits and confirmed by molecular method. These isolates were tested for antimicrobial susceptibilities by disk diffusion method according to the Clinical and Laboratory Standards Institute guidelines. Carbapenem-resistant isolates were further detected phenotypically by MbetaL minimal inhibitory concentration (MIC)-test strips, and subsequently positive MbetaL isolates were confirmed by polymerase chain reaction (PCR). RESULTS: Overall, 98% (96/98) of A. baumannii isolates were detected as carbapenem resistant by MIC test. Highest sensitivity to the tested antibiotic with 42.9% (42/98) was observed to colistin. Of 96 carbapenem-resistant isolates, 43 were phenotypically positive for MbetaL; out of 43 isolates, 37 were confirmed for the presence of MbetaL genes by PCR. CONCLUSION: The frequency of drug resistance among the clinical samples of A. baumannii isolated in our study against most of the antibiotics was very high. Moreover, all MbetaL producing isolates were multidrug resistance. Therefore, systematic surveillance to detect MbetaL producing bacteria and rational prescription and use of carbapenems could be helpful to prevent the spread of carbapenem resistance. PMID- 27398248 TI - Accidental Childhood Poisoning in Enugu, South-East, Nigeria. AB - BACKGROUND: Accidental childhood poisoning is one of the recognized causes of morbidity and mortality in children under the age of 5 years worldwide. The prevalence and type of substance ingested vary from place to place and over time. AIM: This study was conducted with the aim of ascertaining the frequency and pattern of accidental childhood poisoning in Enugu. SUBJECTS AND METHODS: This retrospective study was conducted at the Emergency Paediatric Unit of the University of Nigeria Teaching Hospital, Enugu, South-East, Nigeria from January 2003 to December 2012 (10 years). All the cases of childhood accidental poisoning that presented within the period were reviewed and important information extracted. RESULTS: Sixty-five cases of childhood poisoning were recorded during the 10-year period, giving an incidence rate of 442 per 100,000 children. The mean age was 22.15 +/- 11.7 months. Male:female ratio was 1.5:1. The prevalence was higher among those with low socioeconomic background. Kerosene poisoning was the most common agent. The overall mortality rate was 3.1% (2/65). CONCLUSION: Accidental childhood poisoning is common in Enugu, with appreciable mortality, with kerosene being the most common agent. We advocate regulatory policy on proper ways of storing kerosene and other harmful household chemicals and medications. PMID- 27398249 TI - The Burden of Pulmonary Hypertension in Patients with Degenerative Mitral Valve Disease in Enugu South-East Nigeria: An Echocardiographic Based Study. AB - BACKGROUND: Pulmonary hypertension is a common complication of degenerative mitral valve disease, and contributes significantly to both morbidity and mortality. The use of medications for reduction of pulmonary pressure in patients is not a common practice by most physicians in this part of the world because of the absence of data on pulmonary hypertension. AIM: The authors set out to find the prevalence of pulmonary hypertension in patients with degenerative mitral valve disease and to determine if there are gender differences in affectation. This will form a basis for future research on the management of pulmonary hypertension in sub-Saharan Africa. SUBJECTS AND METHODS: The echocardiographic records of 1390 patients carried out over a period of 4 years were retrospectively reviewed. The examinations were done with a Logic 500 MD echocardiographic machine. Tricuspid valve regurgitation velocity above 250 cm/s defined pulmonary hypertension. Data obtained included presence of degenerative mitral valve disease, pulmonary hypertension, age, and gender. RESULTS: A total of 1390 echocardiogram reports done at Conquest Medical Imaging, Enugu, from July 2009 to August 2013 were retrospectively reviewed. Degenerative mitral valve disease was noted in 18.7% of the patients, (259/1390) made up of 149 males and 110 females with a mean age of 68.3 (14.4) years. Pulmonary hypertension was present in 30% of the patients (78/259) and affected males more than females. CONCLUSION: Pulmonary hypertension is common in patients with degenerative mitral valve disease in Enugu, and affects males more than females. PMID- 27398250 TI - Applicability of Two Universally Accepted Mixed Dentition Analysis on a Sample from Southeastern Region of Andhra Pradesh, India. AB - BACKGROUND: Most of the universally accepted mixed dentition analyses are based on the data derived from northwestern European descent. However, the accuracy of these methods when applied to different ethnic population is questionable. AIM: The present study is aimed to evaluate the applicability of Tanaka and Johnston (TJ) and Moyers (50(th) and 75(th) percentile) mixed dentition analysis in a sample from south-eastern region of Andhra Pradesh, India. SUBJECTS AND METHODS: Study models were prepared from a sample of 100 patients (50 males and 50 females) in the age range of 13-15 years. The mesio-distal dimension of the teeth was measured using a Digital Vernier calipers. The actual values of permanent canine and premolars on the casts were compared with the predicted values from TJ and Moyers analysis. The values derived from this study were statistically analyzed using SPSS version 17.0 (IBM, Chicago, USA). Pearson's coefficients were used to evaluate the correlations between the groups of teeth. RESULTS: Overestimated values were noticed in males and females of both arches with TJ equation; Males showed no significant difference at Moyers 50(th) percentile (50/100), in both the arches where as females showed higher values in mandibular arch and underestimated values in maxillary arch. At Moyers 75(th) percentile, overestimated values were noticed in males for both the arches whereas in females lesser values were observed. CONCLUSION: As the values showed significant deviation from TJ and Moyers both at 50 and 75 percentile, its applicability to the present population is limited. So, new regression equations were derived. PMID- 27398251 TI - Utility of Bacillary Index in Slit Skin Smears in Correlation with Clinical and Histopathological Alterations in Hansen's Disease: An Attempt to Revive a Simple Useful Procedure. AB - Leprosy, a relatively common chronic contagious disease having diverse modes of clinical presentation, can mimic a variety of unrelated diseases. For proper and adequate treatment, the diagnosis must be made accurately with subtyping which should be done with the help of bacillary index, histopathological features, and clinical correlation. This is extremely important in patient care as paucibacillary and multibacillary types have different modes of treatment. Our aim is to categorize leprosy into various types based on bacillary index, morphological findings both in slit skin smears, and biopsy along with clinical correlation. PMID- 27398252 TI - Refining the Journal Club Presentations of Postgraduate Students in Seven Clinical Departments for Better Evidence-based Practice. AB - BACKGROUND: A gap between best practice and actual clinical care exists and this can be overcome by evidence-based practice (EBP), which is essential to improve the clinical decision making. A strategy to reduce deficits in care provision is to train the postgraduate students in the practice of EBP in the journal clubs as evidence from medical colleges in India reveals that current format of journal club presentations is unsatisfactory. AIM: The aim of the present study was to refine the journal club presentations of postgraduate students of clinical departments and to study the effectiveness of EBP training in them for better EBP. SUBJECTS AND METHODS: This study was conducted in S. Nijalingappa Medical College, Bagalkot, Karnataka, India, and it was a pre- and post-trial. This study was a pre- and post-trial done during the journal club presentations of postgraduate students from clinical departments. Postgraduate students' understanding of concepts about EBP was assessed using Fresno test questionnaire in traditional journal club presentation. A hands-on session incorporating steps of EBP was imparted to them. Soon after the session, each student was assessed. In the next journal club presentation, 1 week later, the students were assessed again with the same questionnaire by the same faculty. Scores of the postgraduate students, before and after intervention (immediate and 1 week later), were compared. Data were analyzed by paired t-test using SPSS. RESULTS: An increase in mean posttest scores was seen immediately and also 1 week later as compared to the pretest scores. The scores also increased significantly, when each step of EBP was considered. CONCLUSIONS: Incorporating teaching of EBP in journal club presentations improved the competencies of postgraduate students in clinical decision making. PMID- 27398253 TI - Bi-lobed Perirectal Epidermoid Cyst: An Unusual Cause of Hematochezia in a Middle aged Woman. AB - Perirectal epidermoid cysts are congenital cysts originating from the ectodermal germ cell layer of the hind gut. Their presenting symptoms are most often nonspecific and distinguishing them from other presacral developmental cysts often present a diagnostic and therapeutic dilemma. We present a 58-year-old woman who presented with chronic dyschezia and hematochezia of a few days duration and no prior colonoscopies. Initial blood work and tumor markers were unremarkable. Pelvic magnetic resonance imaging (MRI) showed a 7.5 cm * 5 cm * 6 cm homogenous bi-lobed cystic mass in the pelvis adherent to the left lateral wall of the rectum and posteriorly to the sacrum with a displacement of the rectum anteriorly and to the right. There was no pelvic sidewall adenopathy or free fluid in the pelvis. Preoperative colonoscopy showed rectal compression with no rectal involvement of the mass. The cyst was successfully resected posteriorly via the trans-sacrococcygeal approach. An intraoperative proctosigmoidoscopy confirmed an intact rectum. The patient remains recurrence-free 1 year postsurgical resection. PMID- 27398254 TI - Fabry's Disease: Case Series and Review of Literature. AB - Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells leading to cardiovascular, renal, gastrointestinal, neuropathic, lenticular, and dermatological manifestations. It is a rare cause of end-stage renal disease. It classically affects males whereas 10-15% of female heterozygote carriers are affected depending on localization. Both the FD and its association with ESRD is rare. With this background, this case series of five patient's along with the review of literature is presented here. PMID- 27398255 TI - An Alternative Instrument for Making Entry Point for Elastic Intramedullary Nail. PMID- 27398256 TI - How much effort is required to accurately describe the complex ecology of a rodent-borne viral disease? AB - We use data collected on 18,1-ha live trapping grids monitored from 1994 through 2005 and on five of those grids through 2013 in the mesic northwestern US to illustrate the complexity of the deer mouse (Peromyscus maniculatus)/Sin Nombre virus (SNV) host-pathogen system. Important factors necessary to understand zoonotic disease ecology include those associated with distribution and population dynamics of reservoir species as well as infection dynamics. Results are based on more than 851,000 trap nights, 16,608 individual deer mice and 10,572 collected blood samples. Deer mice were distributed throughout every habitat we sampled and were present during every sampling period in all habitats except high altitude habitats over1900 m. Abundance varied greatly among locations with peak numbers occurring mostly during fall. However, peak rodent abundance occurred during fall, winter and spring during various years on three grids trapped 12 mo/yr. Prevalence of antibodies to SNV averaged 3.9% to 22.1% but no grids had mice with antibodies during every month. The maximum period without antibody-positive mice ranged from one month to 52 months, or even more at high altitude grids where deer mice were not always present. Months without antibody-positive mice were more prevalent during fall than spring. Population fluctuations were not synchronous over broad geographic areas and antibody prevalences were not well spatially consistent, differing greatly over short distances. We observed an apparently negative, but non-statistically significant relationship between average antibody prevalence and average deer mouse population abundance and a statistically significant positive relationship between the average number of antibody positive mice and average population abundance. We present data from which potential researchers can estimate the effort required to adequately describe the ecology of a rodent-borne viral system. We address different factors affecting population dynamics and hantavirus antibody prevalence and discuss the path to understanding a complex rodent-borne disease system as well as the obstacles in that path. PMID- 27398257 TI - Adapting an Evidence-Based HIV-Prevention Intervention for Women in Domestic Violence Shelters. AB - OBJECTIVE: Despite the documented intersection of intimate partner violence and HIV, there is a paucity of evidence-based HIV prevention interventions for female survivors of intimate partner violence in the United States. This paper describes the adaptation of an effective HIV prevention intervention, Sisters Informing Sisters about Topics on AIDS (SISTA), for women in domestic violence shelters and the steps taken to improve the adapted intervention's implementation. METHOD: The adaptation process was guided by the ADAPT-ITT framework and data collected from directors, direct client service providers, and residents of two domestic violence shelters located in urban areas, as well as topical experts. RESULTS: Eleven of 12 shelter staff (92%) reported that HIV interventions had never been implemented at their shelter and 64% reported they had not provided residents with educational brochures about HIV prevention. Changes made to adapt SISTA for this population and enhance the implementation of the intervention included reducing the intervention's duration; adding education about the intersection of intimate partner violence, substance use, and HIV; and adding an HIV risk assessment and safety plan. CONCLUSIONS: Next steps will include implementing the adapted intervention and evaluating its perceived acceptability and efficacy, and assessing whether contextual factors influence the intervention's implementation. PMID- 27398258 TI - Determining Sufficient Number of Imputations Using Variance of Imputation Variances: Data from 2012 NAMCS Physician Workflow Mail Survey. AB - How many imputations are sufficient in multiple imputations? The answer given by different researchers varies from as few as 2 - 3 to as many as hundreds. Perhaps no single number of imputations would fit all situations. In this study, eta, the minimally sufficient number of imputations, was determined based on the relationship between m, the number of imputations, and omega, the standard error of imputation variances using the 2012 National Ambulatory Medical Care Survey (NAMCS) Physician Workflow mail survey. Five variables of various value ranges, variances, and missing data percentages were tested. For all variables tested, omega decreased as m increased. The m value above which the cost of further increase in m would outweigh the benefit of reducing omega was recognized as the eta. This method has a potential to be used by anyone to determine eta that fits his or her own data situation. PMID- 27398259 TI - Fraction of Missing Information (gamma) at Different Missing Data Fractions in the 2012 NAMCS Physician Workflow Mail Survey. AB - In his 1987 classic book on multiple imputation (MI), Rubin used the fraction of missing information, gamma, to define the relative efficiency (RE) of MI as RE = (1 + gamma/m)-1/2, where m is the number of imputations, leading to the conclusion that a small m (<=5) would be sufficient for MI. However, evidence has been accumulating that many more imputations are needed. Why would the apparently sufficient m deduced from the RE be actually too small? The answer may lie with gamma. In this research, gamma was determined at the fractions of missing data (delta) of 4%, 10%, 20%, and 29% using the 2012 Physician Workflow Mail Survey of the National Ambulatory Medical Care Survey (NAMCS). The gamma values were strikingly small, ranging in the order of 10-6 to 0.01. As delta increased, gamma usually increased but sometimes decreased. How the data were analysed had the dominating effects on gamma, overshadowing the effect of delta. The results suggest that it is impossible to predict gamma using delta and that it may not be appropriate to use the gamma-based RE to determine sufficient m. PMID- 27398260 TI - Network Lasso: Clustering and Optimization in Large Graphs. AB - Convex optimization is an essential tool for modern data analysis, as it provides a framework to formulate and solve many problems in machine learning and data mining. However, general convex optimization solvers do not scale well, and scalable solvers are often specialized to only work on a narrow class of problems. Therefore, there is a need for simple, scalable algorithms that can solve many common optimization problems. In this paper, we introduce the network lasso, a generalization of the group lasso to a network setting that allows for simultaneous clustering and optimization on graphs. We develop an algorithm based on the Alternating Direction Method of Multipliers (ADMM) to solve this problem in a distributed and scalable manner, which allows for guaranteed global convergence even on large graphs. We also examine a non-convex extension of this approach. We then demonstrate that many types of problems can be expressed in our framework. We focus on three in particular - binary classification, predicting housing prices, and event detection in time series data - comparing the network lasso to baseline approaches and showing that it is both a fast and accurate method of solving large optimization problems. PMID- 27398262 TI - Palladium-Catalyzed, Enantioselective Heine Reaction. AB - Aziridines are important synthetic intermediates for the generation of nitrogen containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)-diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis. PMID- 27398263 TI - Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines. AB - We reported at the Keynote Forum of Immunology Summit-2015 that recombinant human (rh) TNF-alpha or rhIL-6 stimulated production of matrix metalloproteinase-9 (MMP 9) in the T/C28a2 and C-28/I2 human immortalized chondrocyte cell lines. Furthermore, we reported that tocilizumab (TCZ), a fully humanized monoclonal antibody which neutralizes IL-6-mediated signaling, inhibited the rhIL-6-mediated increase in the production of MMP-9. IL-6 is also a known activator of the JAK/STAT signaling pathway. In that regard, we evaluated the effect of rhIL-6 on total and phosphorylated Signal Transducer and Activator of Transcription by these chondrocyte lines which showed that whereas STAT3 was constitutively phosphorylated in T/C28a2 chondrocytes, rhIL-6 activated STAT3 in C-28/I2 chondrocytes. The finding that rhIL-6 increased the production of MMP-9 by human immortalized chondrocyte cell lines may have important implications with respect to the destruction of articular cartilage in rheumatoid arthritis and osteoarthritis. Thus, the markedly elevated level of IL-6 in rheumatoid arthritis and osteoarthritis sera and synovial fluid would be expected to generate significant MMP-9 to cause the degradation of articular cartilage extracellular matrix proteins. The finding that TCZ suppressed rhIL-6-mediated MMP-9 production suggests that TCZ, currently employed in the medical therapy of rheumatoid arthritis, could be considered as a drug for osteoarthritis. PMID- 27398261 TI - Building Bridges: Biocatalytic C-C-Bond Formation toward Multifunctional Products. AB - Carbon-carbon bond formation is the key reaction for organic synthesis to construct the carbon framework of organic molecules. The review gives a selection of biocatalytic C-C-bond-forming reactions which have been investigated during the last 5 years and which have already been proven to be applicable for organic synthesis. In most cases, the reactions lead to products functionalized at the site of C-C-bond formation (e.g., alpha-hydroxy ketones, aminoalcohols, diols, 1,4-diketones, etc.) or allow to decorate aromatic and heteroaromatic molecules. Furthermore, examples for cyclization of (non)natural precursors leading to saturated carbocycles are given as well as the stereoselective cyclopropanation of olefins affording cyclopropanes. Although many tools are already available, recent research also makes it clear that nature provides an even broader set of enzymes to perform specific C-C coupling reactions. The possibilities are without limit; however, a big library of variants for different types of reactions is required to have the specific enzyme for a desired specific (stereoselective) reaction at hand. PMID- 27398264 TI - The Effects of Dietary Omega-3s on Muscle Composition and Quality in Older Adults. AB - This review will focus on findings from the few studies performed to date in humans to examine changes in muscle protein turnover, lean or muscle mass and physical function following fish oil-derived omega-3 fatty acid treatment. Although considerable gaps in our current knowledge exist, hypertrophic responses (e.g., improvements in the rate of muscle protein synthesis and mTOR signaling during increased amino acid availability and an increase in muscle volume) have been reported in older adults following prolonged (8 to 24 weeks) of omega-3 fatty acid supplementation. There is also accumulating evidence that increased omega-3 fatty acid levels in red blood cells are positively related to strength and measures of physical function. As a result, increased omega-3 fatty acid consumption may prove to be a promising low-cost dietary approach to attenuate or prevent aging associated declines in muscle mass and function. PMID- 27398265 TI - Economics of Musculoskeletal Ultrasound. AB - PURPOSE OF REVIEW: Healthcare costs have exploded in the past 30 years and they are a major concern for governments worldwide. Care management of musculoskeletal disorders and advanced imaging account for a large part of this socioeconomic burden. RECENT FINDINGS: Musculoskeletal ultrasound is now performed primarily by nonradiologists. Both musculoskeletal ultrasound and MRI total utilization rates continue to increase. Despite the existence of evidence-based diagnostic recommendations and the potential cost-savings of using musculoskeletal ultrasound instead of MRI in certain clinical situations, ensuring appropriate use of imaging among health professionals remains difficult for various reasons. SUMMARY: In the context of healthcare budgets restraints, use of imaging must be shown scientifically, to improve patient outcomes and be cost-effective. Current evidence recommends musculoskeletal ultrasound as the primary imaging modality in the investigation of rotator cuff disease. Policies aiming at ensuring the application of imaging guidelines among physicians are needed. PMID- 27398266 TI - Models of fluorescence and photosynthesis for interpreting measurements of solar induced chlorophyll fluorescence. AB - : We have extended a conventional photosynthesis model to simulate field and laboratory measurements of chlorophyll fluorescence at the leaf scale. The fluorescence paramaterization is based on a close nonlinear relationship between the relative light saturation of photosynthesis and nonradiative energy dissipation in plants of different species. This relationship diverged only among examined data sets under stressed (strongly light saturated) conditions, possibly caused by differences in xanthophyll pigment concentrations. The relationship was quantified after analyzing data sets of pulse amplitude modulated measurements of chlorophyll fluorescence and gas exchange of leaves of different species exposed to different levels of light, CO2, temperature, nitrogen fertilization treatments, and drought. We used this relationship in a photosynthesis model. The coupled model enabled us to quantify the relationships between steady state chlorophyll fluorescence yield, electron transport rate, and photosynthesis in leaves under different environmental conditions. KEY POINTS: Light saturation of photosynthesis determines quenching of leaf fluorescenceWe incorporated steady state leaf fluorescence in a photosynthesis model. PMID- 27398267 TI - Extraventricular neurocytoma of the sellar region: case report and literature review. AB - INTRODUCTION: The extraventricular neurocytoma of the sellar region (EVNSR) is a rare disease, it is difficult to make exact diagnosis of and operate on patients. Retrospectively analysed the clinical manifestations, image features, therapy methods and outcomes among patients with EVNSR, to investigate the epidemiological characteristics, image features, diagnosis, treatment and prognosis. CASE DESCRIPTION: A 25-year-old man man with 7-month worsening vision of left eye, was confirmed EVNSR after subtotally resection from the neurosurgical department of Deji hospital. DISCUSSION AND EVALUATION: Nine cases of EVNSR were reported from this article and elsewhere. Ages of these patients were ranging from 25 to 66 (with an average of 45.67). The male-female ratio was 1-2. All EVNSR patients had visual damage. Images showed the tumors were in the sellar and suprasellar regions. Preoperatively, all patients were misdiagnosed as other diseases: such as pituitary tumor, craniopharyngioma, and meningioma. For tumor removal treatment, five patients received transpterional approach, one received subfrontal approach and three received transnostril-transsphenoidal approach. EVNSR was confirmed by pathological tests. The tumor was completely removed in one patient. During the 12-24 month postoperative follow up period, the recurrence or metastasis of the tumor was found in two patients. CONCLUSIONS: EVNSR is a rare disease. It occurs mostly in middle-aged women. EVNSR is likely to be misdiagnosed as pituitary adenoma preoperatively. The histological examination would help confirm the diagnosis. Using transpterional approach to remove tumor will help the prognosis, especially among patients with normal pituitary function. Both postoperative radiotherapy and long-term follow-up are recommended. PMID- 27398268 TI - The reduced PDCD5 protein is correlated with the degree of tumor differentiation in endometrioid endometrial carcinoma. AB - Endometrial cancer is one of the most common malignancies in the female genital tract. Programmed cell death 5 (PDCD5) is a newly identified apoptosis related gene and plays an important role in the development of some human tumors. However, the expression and clinical significance of PDCD5 in endometrial cancer have not been fully elucidated. Here, we evaluated the expression of PDCD5 in endometrioid endometrial carcinoma and control endometrium by qRT-PCR, western blot and immunohistochemistry, and analyzed the associations of PDCD5 expression with clinicopathological parameters of patients. In addition, we detected the expression of PDCD5 in control endometrial glandular epithelial cells and endometrioid endometrial carcinoma-derived cell line KLE by immunocytochemistry. The results showed that PDCD5 protein mainly expressed in the cytoplasm of glandular epithelial cells and endometrial carcinoma cells, and there was a low level of PDCD5 expression in the nuclei of the above cells. Furthermore, PDCD5 protein level was significantly lower in endometrial carcinoma samples than that in control endometrium. The decreased PDCD5 expression was correlated with the tumor differentiation degree. It is clear that PDCD5 protein expression was lower in middle and low differentiated endometrial carcinoma compared with control endometrium and high differentiated endometrial carcinoma. However, there were no significant differences of PDCD5 expression between the proliferative phase and the secretory phase of control endometrium, as well as between high differentiated endometrial carcinoma and controls. The results were verified in control glandular epithelial cells and KLE cells by immunocytochemistry. Therefore, PDCD5 may play a key role in the pathogenesis of endometrial cancer and may be a novel target for diagnosis and treatment of endometrial cancer. PMID- 27398269 TI - The effect of the immune system on ovarian function and features of ovarian germline stem cells. AB - In addition to its role in maintaining organism homeostasis, the immune system also plays a crucial role in the modulation of ovarian function, as it regulates ovarian development, follicular maturation, ovulation and the formation of the corpus luteum. Ovarian germline stem cells are pluripotent stem cells derived from the ovarian cortex that can differentiate into ovarian germ cells and primary granulosa cells. Recent work has demonstrated that the proliferation and differentiation of ovarian germline stem cells is regulated in part by immune cells and their secreted factors. This paper reviews the role of the immune system in the regulation of ovarian function, the relationship between immune components and ovarian germline stem cells and current research efforts in this field. PMID- 27398270 TI - Apoptotic action of botulinum toxin on masseter muscle in rats: early and late changes in the expression of molecular markers. AB - The purpose of this study was to compare the early or late expression levels of p65, Bcl-2, and type II myosin and the frequency of TUNEL-positive nuclei in the rat masseter muscle after injection of different concentrations of botulinum toxin-A (BTX-A). We injected either 5 U or 10 U of BTX-A into both masseter muscles of the rat. As a control group, the same volume of saline was injected. After 2 or 12 weeks, the animals were sacrificed. Subsequently, a biopsy and immunohistochemical staining of the samples were performed using a p65, Bcl-2, or type II myosin antibody. Additionally, a TUNEL assay and transmission electron microscopic analysis were performed. The expression of p65, Bcl-2, and type II myosin increased significantly with increasing concentrations of BTX-A at 2 weeks after BTX-A injection (P < 0.05). The number of TUNEL-positive nuclei was also significantly increased in the BTX-A-treated groups in comparison to the saline treated control at 2 weeks after BTX-A injection (P < 0.05). Elevated expression of Bcl-2 was also observed in 10-unit BTX-A-treated group at 12 weeks after injection (P < 0.05). At 12 weeks after injection, the number of enlarged mitochondria was increased, and many mitochondria displayed aberrations in cristae morphology after BTX-A injection. In conclusion, BTX-A injection into the masseter muscle increased the expression level of p65, Bcl-2, and type II myosin at an early stage. The morphological changes of mitochondria were more evident at 12 weeks after injection. PMID- 27398271 TI - Artemisia dominant species succession relating to the soil moisture decrease in abandoned land of the Loess Plateau (China): comparative study of drought adaptive characteristics. AB - Artemisia scoparia, Artemisia sacrorum and Artemisia giraldii were three dominant Artemisia species which successive grew in the secondary succession on abandoned land of the Loess Plateau. The succession accompanied the soil moisture steady decrease with field age after their abandonment. To elucidate the relationship between the Artemisia species succession and their drought-adaptation, three dominant species and a contrastive species Artemisia annua (mesophyte), were selected to compare their drought-resistant characteristics, including morphological and anatomical traits of leaf and root. Then physiological responses were investigated in mature plants after drought treatment. The results indicated that three dominant species leaf presented drought-adaptive structures, such as bushy trichomes, transitional or isolateral leaf cells, thick cuticles and epidermal cells. However, A. annua had no leaf traits involved in drought adaptation. In addition, A. sacrorum and A. giraldii contained large root systems, while A. scoparia and A. annua utilized succulent roots. The physiological responses to drought suggested that A. giraldii had strong regulation in water using strategy, growth, as well as superoxide dismutase and catalase activity. A. sacrorum and A. giraldii could maintain high ascorbate peroxidase activity and malondialdehyde content, while A. scoparia and A. giraldii presented higher peroxidase activity, ascorbate and soluble sugar content. A. annua exhibited high proline and carotenoid contents under drought. The drought-resistant of the four Artemisia species presented the order of A. giraldii > A. sacrorum > A. scoparia > A. annua, which was consistent with their succession on abandoned land. PMID- 27398273 TI - Retroperitoneal laparoscopic partial nephrectomy for treatment of metanephric adenoma (Report of 6 cases). AB - OBJECTIVES: To investigate the clinical and pathological features of metanephric adenoma (MA) and the clinical outcome after retroperitoneal laparoscopic nephron sparing surgery. METHODS: Six out of 183 partial nephrectomies performed during January 2009 to August 2014 were confirmed to be MA confirmed by postoperative pathological study. Perioperative parameters of the six patients were then retrospectively collected, analyzed and compared with current literature, including warm ischemia time (WIT), total operation time, estimated blood loss (EBL), positive surgical margin (PSM), and complications. Surgical and oncological outcome of all six patients were evaluated based on a mean follow up of 17 months (5-48 months). RESULTS: Tumors in all six cases were all successfully removed by partial nephrectomy. Mean WIT was 24.7 min (19-35 min). Mean operation time was 103.6 min (82-147 min). Mean EBL was 53.5 ml (20-85 ml). No conversion, transfusion or other major complication were observed in all six cases. Postoperative pathology confirmed negative surgical margin in all six cases. During a mean of 17 month follow up (5-48 months), no local recurrence or metastasis were found in all six cases. CONCLUSION: MA is a rare benign primary kidney epithelial cancer, which could hardly be differentiated from renal malignancies based on preoperative imaging. Our data suggested that retroperitoneal laparoscopic partial nephrectomy can be used for surgical treatment of MA, in terms of tumor control and preservation of renal function. PMID- 27398272 TI - Potential beneficial effects of a gluten-free diet in newly diagnosed children with type 1 diabetes: a pilot study. AB - AIM: Gluten-free diet has shown promising effects in preventing type 1 diabetes (T1D) in animals as well as beneficial effects on the immune system. Gluten-free diet at diabetes onset may alter the natural course and outcome of autoimmune diseases such as T1D. METHODS: In a 12-month study, 15 children newly diagnosed with T1D were instructed to follow a gluten-free diet. Questionnaires were used to evaluate adherence to the gluten-free diet. Partial remission (PR) was defined by insulin dose-adjusted A1c (IDAA1c) <=9 or stimulated C-peptide (SCP) >300 pmol/L measured 90 min after a liquid mixed meal at the inclusion, six and 12 months after onset. The intervention group was compared with two previous cohorts. Linear mixed models were used to estimate differences between cohorts. RESULTS: After 6 months, more children on a gluten-free diet tended to have SCP values above 300 pmol/L compared to the European cohort (p = 0.08). The adherence to a gluten-free diet decreased during the 12-month study period. After 1 year there was no difference in SCP levels or percentage in remission according to SCP (p > 0.1). Three times as many children were still in PR based on IDAA1c (p < 0.05). Twelve months after onset HbA1c were 21 % lower and IDAA1c >1 unit lower in the cohort on a gluten-free diet compared to the two previous cohorts (p < 0.001). CONCLUSION: Gluten-free diet is feasible in highly motivated families and is associated with a significantly better outcome as assessed by HbA1c and IDAA1c. This finding needs confirmation in a randomized trial including screening for quality of life. (Clinicaltrials.gov number NCT02284815). PMID- 27398274 TI - Preparation of a functional fluorescent human Fas ligand extracellular domain derivative using a three-dimensional structure guided site-specific fluorochrome conjugation. AB - BACKGROUND: Human Fas ligand extracellular domain has been investigated as an important target protein in the field of medical biotechnology. In a recent study, the author developed an effective method to produce biologically active human Fas ligand extracellular domain derivatives using site-specific chemical modifications. FINDINGS: A human Fas ligand extracellular domain derivative containing a reactive cysteine residue within its N-terminal tag sequence, which locates not proximal to the binding interface between the ligand and the receptor in terms of the three-dimensional structure, was modified by Fluorescein-5 Maleimide without impairing the specific binding activity toward human Fas receptor extracellular domain. The purified protein sample free of low molecular weight contaminants showed a characteristic fluorescence spectrum derived from the attached Fluorescein moieties, and formed a stable binding complex with human Fas receptor extracellular domain-human IgG1 Fc domain fusion protein in solution. The conjugation number of the fluorochrome was estimated to be 2.5 per a single human Fas ligand extracellular domain trimer from the ratio of the absorbance value at 280 nm to that at 495 nm. CONCLUSIONS: A functional fluorescent human Fas ligand extracellular domain derivative was prepared via a site-specific conjugation of fluorochrome, which was guided by the three dimensional structure information on the ligand-receptor complex. Fluorescent derivatives created by this method may contribute to the development of an improved diagnosis system for the diseases related to Fas receptor. PMID- 27398275 TI - Liver stiffness-spleen size-to-platelet ratio risk score detects esophageal varices in chronic liver disease. AB - BACKGROUND: Noninvasive markers are needed to identify esophageal varices (EV) in patients with chronic liver disease (CLD). Recently, liver stiffness (LS)-spleen size-to-platelet ratio risk score (LSPS) has been shown to predict EV in patients with chronic hepatitis C. The aim of this study was to validate the clinical value of LSPS for EV detection and identification of high risk EV in Japanese patients with CLD. METHODS: A total of 230 patients with CLD who had undergone endoscopy, LS measurement, and ultrasonography between 2013 and 2015 were enrolled. The relationships between clinical data and LSPS were compared with those for other noninvasive markers (aspartate aminotransferase-to-platelet ratio, FIB-4 index, and platelet-to-spleen ratio), along with platelet count, spleen size, and LS. Diagnostic and prognostic abilities were assessed by the area under the receiver operating characteristic curve (AUC) and multivariate logistic regression. RESULTS: LSPS correlated significantly with EV grade (P < 0.001) and was superior to the other noninvasive indices for determination of EV and high risk EV. Furthermore, LSPS was independently associated with the presence of EV (P < 0.001) and elevated EV risk (P = 0.013) by multivariate logistic regression analysis. The optimal cutoff values of LSPS for EV and high risk EV were 1.1 and 2.2, respectively, at which AUC, negative predictive value, and accuracy were 0.821 [95 % confidence interval (CI) 0.743-0.899], 91.9, and 84.3 % and 0.859 (95 % CI 0.736-0.981), 95.5, and 76.9 %, respectively. CONCLUSIONS: LSPS represents a useful, noninvasive, accurate method to detect EV and a high EV risk in Japanese patients with CLD. PMID- 27398277 TI - The impact of relative energy prices on industrial energy consumption in China: a consideration of inflation costs. AB - Significant effort has been exerted on the study of economic variables such as absolute energy prices to understand energy consumption and economic growth. However, this approach ignores general inflation effects, whereby the prices of baskets of goods may rise or fall at different rates from those of energy prices. Thus, it may be the relative energy price, not the absolute energy price, that has most important effects on energy consumption. To test this hypothesis, we introduce a new explanatory variable, the domestic relative energy price, which we define as "the ratio of domestic energy prices to the general price level of an economy," and we test the explanatory power of this new variable. Thus, this paper explores the relationship between relative energy prices and energy consumption in China from the perspective of inflation costs over the period from 1988 to 2012. The direct, regulatory and time-varying effects are captured using methods such as ridge regression and the state-space model. The direct impacts of relative energy prices on total energy consumption and intensity are -0.337 and 0.250, respectively; the effects of comprehensive regulation on energy consumption through the economic structure and the energy structure are -0.144 and -0.148, respectively; and the depressing and upward effects of rising and falling energy prices on energy consumption are 0.3520 and 0.3564, respectively. When economic growth and the energy price level were stable, inflation persisted; thus, rising energy prices benefitted both the economy and the environment. Our analysis is important for policy makers to establish effective energy-pricing policies that ensure both energy conservation and the stability of the pricing system. PMID- 27398276 TI - Formal analysis of imprecise system requirements with Event-B. AB - Formal analysis of functional properties of system requirements needs precise descriptions. However, the stakeholders sometimes describe the system with ambiguous, vague or fuzzy terms, hence formal frameworks for modeling and verifying such requirements are desirable. The Fuzzy If-Then rules have been used for imprecise requirements representation, but verifying their functional properties still needs new methods. In this paper, we propose a refinement-based modeling approach for specification and verification of such requirements. First, we introduce a representation of imprecise requirements in the set theory. Then we make use of Event-B refinement providing a set of translation rules from Fuzzy If-Then rules to Event-B notations. After that, we show how to verify both safety and eventuality properties with RODIN/Event-B. Finally, we illustrate the proposed method on the example of Crane Controller. PMID- 27398278 TI - Fuzzy logic based on-line fault detection and classification in transmission line. AB - This study presents fuzzy logic based online fault detection and classification of transmission line using Programmable Automation and Control technology based National Instrument Compact Reconfigurable i/o (CRIO) devices. The LabVIEW software combined with CRIO can perform real time data acquisition of transmission line. When fault occurs in the system current waveforms are distorted due to transients and their pattern changes according to the type of fault in the system. The three phase alternating current, zero sequence and positive sequence current data generated by LabVIEW through CRIO-9067 are processed directly for relaying. The result shows that proposed technique is capable of right tripping action and classification of type of fault at high speed therefore can be employed in practical application. PMID- 27398279 TI - A randomized controlled study comparing a vessel sealing system with the conventional technique in axillary lymph node dissection for primary breast cancer. AB - OBJECTIVE: This study aimed to compare the efficacy and safety of the newest bipolar vessel sealing system (BVSS; LigaSureTM Small Jaw) to that of conventional technique in axillary dissection. METHODS: Sixty-one patients with breast cancer were randomized to a conventional dissection surgical technique (CONV group; n = 30) by scalpel and monopolar cautery or that using a vessel sealing system (BVSS group; n = 31). RESULTS: There was a significant difference between both groups in the mean number of days until drain removal (6.4 +/- 2.9 vs. 8.2 +/- 3.8 days; P value = 0.033), and the mean total volume of drainage fluid (365.3 +/- 242.2 vs. 625.1 +/- 446.6 mL; P value = 0.009). The incidence of seroma was similar in both groups (43.3 vs. 37.9 %; P value = 0.673). There was no statistically significant difference in axillary dissection operating time (66 vs. 70 min; P value = 0.371), or the mean volume of blood loss (18.2 +/- 31.1 vs. 20.6 +/- 26.3 mL; P value = 0.663). CONCLUSIONS: Our results suggest that BVSS is a more effective device when compared to the conventional techniques in axillary dissection. PMID- 27398280 TI - Does complementary and alternative medicine (CAM) use reduce negative life impact of headaches for chronic migraineurs? A national survey. AB - BACKGROUND: Chronic migraine is a disabling condition that impacts multiple aspects of migraineurs' lives. Although pharmacological treatments can help to treat the pain associated with migraine headache, chronic migraineurs often experience side-effects of pharmacological treatments. Those experiences may contribute to the observed growth in complementary and alternative medicine (CAM) use among migraineurs. Relatively little is known about the patterns of CAM treatment and the characteristics of chronic migraineurs. Therefore, the purpose of the present study is to investigate the characteristics of chronic migraineurs who use CAM treatment and the relationship among satisfaction with current CAM use, negative life impact, migraine outcomes, and psychiatric comorbidities among chronic migraineurs. METHODS: 2907 participants were recruited from a well-known online migraine headache resource. All participants were US adults aged 18 years or older. Migraineurs are referred to this website through various routes (e.g., referral from healthcare providers, internet search, obtaining information from research papers, personal invitation from other users, and information shared on social media etc.). Participants completed a 30-min self-report-survey in the spring of 2014. RESULTS: Almost half of the participants reported that they are currently using more than three different CAM treatments even though the majority of the participants reported neutral or dissatisfied with their current CAM treatment. Chronic migraineurs who use CAM treatments were more likely to experience prolonged or frequent migraine headaches (p = .018, eta(2) = .0021), and experience greater negative life impact from their headaches (p = .000, eta(2) = .0172) compared to non-CAM users. CAM treatment satisfaction was inversely related to the number of psychiatric comorbidities, frequency of migraines, and number of migraine symptoms (p's < .05). However, CAM treatment satisfaction was more strongly correlated with migraine outcomes than psychiatric comorbidities. CONCLUSIONS: Chronic migraineurs often pursue multiple CAM treatments in spite of low levels of satisfaction with those treatments. Patients who experience relief from traditional treatments are less likely to seek the out additional CAM treatments. Thus it is often the sicker migraine patients who use CAM. More attention is needed to consider migraine treatment resistance, and psychological factors in planning the treatment of chronic migraineurs as those factors may play an important role in treatment choices by patients. PMID- 27398281 TI - QoE collaborative evaluation method based on fuzzy clustering heuristic algorithm. AB - At present, to realize or improve the quality of experience (QoE) is a major goal for network media transmission service, and QoE evaluation is the basis for adjusting the transmission control mechanism. Therefore, a kind of QoE collaborative evaluation method based on fuzzy clustering heuristic algorithm is proposed in this paper, which is concentrated on service score calculation at the server side. The server side collects network transmission quality of service (QoS) parameter, node location data, and user expectation value from client feedback information. Then it manages the historical data in database through the "big data" process mode, and predicts user score according to heuristic rules. On this basis, it completes fuzzy clustering analysis, and generates service QoE score and management message, which will be finally fed back to clients. Besides, this paper mainly discussed service evaluation generative rules, heuristic evaluation rules and fuzzy clustering analysis methods, and presents service based QoE evaluation processes. The simulation experiments have verified the effectiveness of QoE collaborative evaluation method based on fuzzy clustering heuristic rules. PMID- 27398282 TI - Baseline characteristics in female cancer patients with unimproved work status after an outpatient rehabilitation program and health changes during the intervention. AB - PURPOSE: To improve work ability and health-related quality of life (HRQOL) cancer patients were offered a "Rapid-Return to Work" program. However, several patients did not improve their work status after completing the program. The first aim of this study was to identify the proportion of patients with unimproved work status 6 months after the program (follow-up). The second aim was to identify baseline characteristics associated with unimproved work status and the third aim to measure changes in HRQOL from baseline to follow-up in the unimproved compared to the improved group. METHODS: The program consisted of patient education, group discussions and physical activity during a full day weekly for 7 weeks. All patients completed a questionnaire at baseline and follow up, covering demographic-, cancer-related-, co-morbidity and lifestyle variables, HRQOL (EORTC QLQ-C30) and fatigue (Fatigue Questionnaire). RESULTS: 106 female cancer patients completed the program and responded to the follow-up. Thirty-six percent had unimproved work status. Patients in the unimproved group more frequently were in paired relations and had more fatigue at baseline than the improved group. Whereas patients in the improved group increased in 14 of 19 HRQOL parameters, the unimproved group increased in seven of these parameters. Both groups experienced improvement concerning fatigue. CONCLUSION: After the program more than one third of the participants did not improve their work status. Patients in paired relations and with more fatigue at baseline were more likely to have unimproved work status. Those within the unimproved group experienced less improvement in HRQOL parameters during the program than those in the improved group. PMID- 27398283 TI - Distant metastasis detected by routine staging in breast cancer patients participating in the national German screening programme: consequences for clinical practice. AB - PURPOSE: To determine frequency of routine radiological staging of breast cancer patients diagnosed in a German Breast Cancer Screening Center from 2007 to 2014, the incidence and consequences of distant metastases detected and the resulting implications for clinical routine. METHODS: Records of 896 patients with primary breast cancer diagnosed in the Screening Centre and treated in five participating hospitals were analyzed retrospectively. Evaluation included frequency and type of staging procedures and results with respect to distant metastasis and their consequences on clinical management. RESULTS: 894/896 Patients (99.8 %) received staging for distant metastases by bone scintigraphy, chest X-ray and liver sonography and/or CT/MRT diagnostics. Distant metastasis was suggested In 6/894 patients but excluded in 3 by further diagnostics or clinical course. Thus, 3 (0.3 %) were clinically verified to have metastatic disease in bone (n = 2; both pT2) or in bone and lung (n = 1; cT4, cN3). CONCLUSION: Due to the low incidence of verified metastatic disease, the high false positive rate of staging procedures and the unfavorable cost/benefit ratio routine radiological staging should be completely omitted in asymptomatic breast cancer patients diagnosed in a breast cancer screening programme. PMID- 27398284 TI - Do remittances promote financial development in Africa? AB - The paper seeks to establish whether or not remittances promoted financial developments and explore the traceable causality between remittances and financial developments in some countries in Africa. We examine the association between remittances received and how they affect the availability of credit to private sector, bank deposits intermediated by financial institutions and money supply. We also question whether the development in the financial sector causes higher levels or otherwise of remittances received. This paper uses data on remittance flows to 50 developing countries in Africa from 1990 to 2011 to explore the nexus. The study uses fixed effects and random effect estimations as well as Vector Error Correction Model method on the panel data. The study shows that remittances promote certain aspects of financial development to some extent and better financial system foster receipts of remittances. The effect of causality is seen in the short run and not in the long-run. The study alludes to literature that remittances could promote financial development in the short run and the development of the financial sector helps increase the propensity to remit via formal channels. PMID- 27398285 TI - Erratum to: Dynamic contrast-enhanced breast MRI at 7T and 3T: an intra individual comparison study. AB - [This corrects the article DOI: 10.1186/s40064-015-1654-7.]. PMID- 27398286 TI - The Brain-Gut-Microbiome Axis: What Role Does It Play in Autism Spectrum Disorder? AB - The brain-gut-microbiome axis refers to the interactions between the central nervous system, gastrointestinal system, and microorganisms that live in the gastrointestinal tract. Exploring these interactions provides a rationale for why gastrointestinal disorders commonly occur in children with Autism Spectrum Disorders (ASD). Signs of altered brain-gut interactions that are closely associated with functional GI disorders (FGIDs) commonly occur in children with ASD. Studies of microbiome in ASD suggest that changes in the gut microbiome may be associated with ASD and with GI disorders in children with ASD. Further studies into the brain-gut-microbiome axis could lead to new techniques for identifying GI disorders in children with ASD and novel therapies for treating ASD behaviors. PMID- 27398287 TI - Immunotherapy for Head and Neck Squamous Cell Carcinoma. AB - Head and neck squamous cell carcinoma has been found to be an immunosuppressive malignancy, with many defects in the host immune system contributing to the progression of disease. A greater understanding of these defects has lead to the identification and investigation of new therapeutic strategies, targeting immune system dysfunction in an effort to improve the outcomes of this disease. This article provides a brief review of the knowledge regarding the immune defects present in head and neck cancer, as well as a review of the current therapeutic strategies being investigated for use. PMID- 27398288 TI - A Review of Brain Stimulation Treatments for Late-Life Depression. AB - Opinion Statement Recurrence, relapse and resistance to first-line therapies are common and pervasive issues in the treatment of depression in older adults. As a result, brain stimulation modalities are essential treatment options in this population. The majority of data for the effectiveness of brain stimulation modalities comes from electroconvulsive therapy (ECT) studies. Current ECT trials are focused on prolonging response after a successful course and mitigating the cognitive adverse effects. Newer forms of brain stimulation have emerged; unfortunately, as with most advances in medicine older adults have not been systematically included in clinical trials. Repetitive transcranial magnetic stimulation has demonstrated efficacy in younger adults and there is emerging data to support its use in late-life depression (LLD). It will be imperative that older adults be included in future transcranial direct current stimulation and magnetic seizure therapy clinical trials. Unclear efficacy results are a concern for both vagus nerve stimulation and deep brain stimulation. PMID- 27398289 TI - Heart Failure Among Older Adults in Skilled Nursing Facilities: More of a Dilemma Than Many Now Realize. AB - Post-acute care, encompassing long-term care hospitals, home health, inpatient rehabilitation, and skilled nursing facilities, is increasingly employed as an integral part of management for more complicated patients, particularly as hospitals seek to maintain costs and decrease length of stay. Skilled nursing facilities (SNFs) in particular are progressively utilized for patients with complex medical processes, including today's growing population of older hospitalized heart failure (HF) patients who pose a prominent challenge due to their high risks of mortality, 30-day readmissions, and substantial aggregate cost burden to the healthcare system. Publications to date have largely grouped post-hospitalized HF patients together when reporting demographic or outcome data, without differentiating those at SNFs from those at traditional nursing homes or other post-acute care settings. SNF patients suffer distinctive vulnerabilities and needs, and understanding these distinctions has implications for determining goals of care. In this review we evaluate HF patients referred to SNFs, and discuss the characteristics, outcomes, and management challenges associated with this particular population. PMID- 27398290 TI - Upon Further Reflection: View from the Other Side of "Windows on the 21st Century". AB - Three points discussed in Glenn (1993) are reviewed in the context of current events: the discipline of behavior analysis as a cultural system, the importance of that discipline in the training and regulation of behavior analytic practitioners, and Association for Behavior Analysis International (ABAI) as a cultural subsystem that links to all the other parts and therefore links the other parts to one another. Noting similarities between behavior analysis and biology, I consider the growth of biological sciences as a model for behavior analysis. Of particular importance for biology has been the role of basic biological sciences in the practice of medicine and the resulting feedback loops that have developed among its basic sciences, applied sciences, and medical practice. I suggest that behavior analysis explicitly follow this model and that ABAI has a critical role to play in leading the field to developing the feedback loops that have integrated the biological sciences and medicine. PMID- 27398291 TI - A Broad Overview and Review of CRISPR-Cas Technology and Stem Cells. AB - The pinnacle of four decades of research, induced pluripotent stem cells (iPSCs), and genome editing with the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR) now promise to take drug development and regenerative medicine to new levels and to enable the interrogation of disease mechanisms with a hitherto unimaginable level of model fidelity. Autumn 2014 witnessed the first patient receiving iPSCs differentiated into retinal pigmented epithelium to treat macular degeneration. Technologies such as 3D bioprinting may now exploit these advances to manufacture organs in a dish. As enticing as these prospects are, these technologies demand a deeper understanding, which will lead to improvements in their safety and efficacy. For example, precise and more efficient reprogramming for iPSC production is a requisite for wider clinical adoption. Improving awareness of the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) and genomic epigenetic status will contribute to the achievement of these aims. Similarly, increased efficiency, avoidance of off target effects, and expansion of available target sequences are critical to the uptake of genome editing technology. In this review, we survey the historical development of genetic manipulation and stem cells. We explore the potential of genetic manipulation of iPSCs for in vitro disease modeling, generation of new animal models, and clinical applicability. We highlight the aspects that define CRISPR-Cas as a breakthrough technology, look at gene correction, and consider some important ethical and societal implications of this approach. PMID- 27398292 TI - The Risk of Specific Congenital Anomalies in Relation to Newer Antiepileptic Drugs: A Literature Review. AB - BACKGROUND: More information is needed about possible associations between the newer anti-epileptic drugs (AEDs) in the first trimester of pregnancy and specific congenital anomalies of the fetus. OBJECTIVES: We performed a literature review to find signals for potential associations between newer AEDs (lamotrigine, topiramate, levetiracetam, gabapentin, oxcarbazepine, eslicarbazepine, felbamate, lacosamide, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, vigabatrin, and zonisamide) and specific congenital anomalies. METHODS: We searched PubMed and EMBASE to find observational studies with pregnancies exposed to newer AEDs and detailed information on congenital anomalies. The congenital anomalies in the studies were classified according to the congenital anomaly subgroups of European Surveillance of Congenital Anomalies (EUROCAT). We compared the prevalence of specific congenital anomalies in fetuses exposed to individual AEDs in the combined studies with that of the general population in a reference database. A significantly higher prevalence based on three or more fetuses with anomalies was considered a signal. RESULTS: Topiramate showed a higher rate of congenital anomalies than the other newer AEDs. Four signals were found. The signals for associations between topiramate and cleft lip with/without cleft palate and hypospadias were considered strong. Associations between lamotrigine and anencephaly and transposition of great vessels were found within one study and were not supported by other studies. No signals were found for the other newer AEDs, or the information was too limited to provide such a signal. CONCLUSION: In terms of associations between monotherapy with a newer AED in the first trimester of pregnancy and a specific congenital anomaly, the signals for topiramate and cleft lip with/without cleft palate and hypospadias should be investigated further. PMID- 27398293 TI - Drug-Induced Subacute Cutaneous Lupus Erythematosus Associated with Proton Pump Inhibitors. AB - Subacute cutaneous lupus erythematosus (SCLE) is an autoimmune disease that may be induced by proton pump inhibitors (PPIs) in at-risk populations. The US FDA does not recognize SCLE as an adverse event associated with PPIs. We queried the FDA Adverse Event Reporting System database, which contains adverse event case reports submitted by the public as well as by industry, and analyzed the data to quantify passive pharmacovigilance signals for SCLE associated with PPIs. A disproportionality analysis of the signals yielded a significant association between SCLE and PPIs. Discontinuation of PPI resulted in remission, with PPI re challenge causing SCLE to reoccur. A follow-up analysis also yielded a significant association between SCLE and H2 receptor antagonists. We conducted a brief literature survey of published case reports and studies to discern the validity of PPI-induced SCLE signals. Healthcare prescribers and patients should be made aware that SCLE can be induced by PPIs. In such cases, PPIs should be discontinued and alternative clinical treatment sought. Regulatory bodies such as the FDA should incorporate the adverse reaction in PPI prescription labels. PMID- 27398294 TI - Survey of Physicians' Understanding of Specific Risks Associated with Retigabine. AB - BACKGROUND: Following reports of discoloration, including retinal pigmentation, in addition to known significant risks of urinary retention, central nervous system effects, and QTc prolongation, the retigabine indication was restricted to adjunctive treatment of partial onset seizures where other appropriate drug combinations have proved inadequate or have not been tolerated. OBJECTIVE: To ascertain the effectiveness of educational initiatives as reflected in physicians' understanding of retigabine-associated risks, management, and patient selection. METHODOLOGY: An online, cross-sectional survey, designated a post authorization safety study (24/9/2014-30/1/2015), recruited retigabine prescribers (RP) and retigabine non-prescribers (RNP) in seven countries, who had been sent a retigabine Dear Health Care Professional letter (June 2013). Questions tested understanding of the significant risks associated with retigabine. RESULTS: 414/467 participants completed all questions (RP, n = 141; RNP, n = 273) and were included in the analysis. 74.2 % of these participants (RP, 77.3 %; RNP, 72.5 %) correctly identified the label indication. 81.9 % of participants (RP, 86.5 %; RNP, 79.5 %) recognized that specific retigabine associated risks included pigment changes of ocular tissues, including the retina. 81.6 % of participants (RP, 87.2 %; RNP, 78.8 %) recognized that a comprehensive ophthalmologic examination is required. 99.8 % of participants (RP, 100.0 %; RNP, 99.6 %) acknowledged the requirement for action in case of retinal pigmentation or vision changes. RP and RNP results were similar to the overall participants' analysis, with a trend toward stronger understanding among RP. CONCLUSION: Most participants recognized the appropriate population for retigabine treatment and the requirement to monitor for adverse events including retinal pigmentation and vision changes. Understanding was satisfactory among RNP but stronger among RP. PMID- 27398295 TI - Use of Chronic Medications Among Patients with Non-Valvular Atrial Fibrillation. AB - BACKGROUND: Frequency of administration (once daily versus more than once daily) is believed to be an important consideration affecting drug choice. OBJECTIVE: The aim of this study was to describe the characteristics of patients with non valvular atrial fibrillation (NVAF) and the extent to which they take chronic medications, other than anticoagulants, more frequently than once daily. METHODS: Using data from a large, national database of health insurance claims, patients with a diagnosis of NVAF between 1 July 2008 and 30 September 2011 were identified, along with their prescription medications, to determine the proportion of patients taking chronic medications more than once a day. Prescription medications, co-morbidities, and CHADS2 and CHA2DS2-VASc scores were evaluated. CHADS2 assesses the risk of stroke in NVAF patients with the following risk factors: Congestive heart failure, Hypertension, Age >=75 years, Diabetes mellitus, and history of prior Stroke or transient ischemic attack. The CHA2DS2 VASc score adds the following risk factors to the CHADS2 score: Age 65-74 years, Vascular Disease, and Sex Category (Female). RESULTS: Overall, 324,172 patients with NVAF with mean CHADS2 and CHA2DS2-VASc scores of 1.51 and 3.08, respectively, were included in the study. Of these patients, 299,716 (92.5 %) took chronic medications, with an average of 6.9 medications per patient, and 215,527 (66.5 % of all patients or 71.9 % of those taking chronic medications) took medications more than once per day. CONCLUSION: Use of chronic medications other than anticoagulants is common among patients with NVAF, and medications are typically taken multiple times per day. The average number of medications per patient and multiple therapeutic classes prescribed underscore the clinical complexity of NVAF patients. Hence, the choice of a once daily anticoagulant versus a more than once daily anticoagulant may be less relevant in a real world NVAF population in terms of a potential convenience benefit. PMID- 27398296 TI - Persistence of Antipsychotic Treatment in Elderly Dementia Patients: A Retrospective, Population-Based Cohort Study. AB - BACKGROUND: Antipsychotics are commonly used to manage behavioral and psychological symptoms of dementia. Concerns over their safety and efficacy in this role have resulted in antipsychotics typically being recommended for short term usage only when used among dementia patients. However, there is little work examining the duration of antipsychotic treatment in the elderly dementia patient population. OBJECTIVE: To determine the persistence of use of antipsychotics in elderly dementia patients and the role of dose on therapy duration. METHODS: A retrospective, population-based cohort study using administrative data, including dispensing records from a provincial public drug program, from Ontario, Canada between 2009 and 2012. Elderly dementia patients newly initiated onto antipsychotics were followed until drug discontinuation, death, 2-year follow-up, or end of study. Competing risk analysis was performed to determine time to discontinuation, stratified by categories of initial dose. RESULTS: After 2 years 49.1 % of the cohort (N = 22,927 of 46,695) had discontinued treatment. When stratified by dose, the high-dose group (51.1 % discontinued) discontinued more frequently than the medium- (48.7 % discontinued) and low- (47.5 % discontinued) dose groups (p < 0.0001). CONCLUSION: Approximately half of elderly dementia patients treated with antipsychotics discontinue within 2 years, with those on higher doses more likely to discontinue. However, the number of patients remaining on therapy represents a serious public health concern. PMID- 27398297 TI - Changes in Body Image in Patients with Prostate Cancer over 2 Years of Treatment with a Gonadotropin-Releasing Hormone Analogue (Triptorelin): Results from a Belgian Non-Interventional Study. AB - BACKGROUND: Androgen deprivation therapy has been associated with worsened body image in prostate cancer patients. Body image and physical presentation changes were investigated in patients receiving a gonadotropin-releasing hormone analogue (triptorelin) as part of treatment for locally advanced or metastatic prostate cancer. OBJECTIVE: The aim was to evaluate the changes in self-perception of the body and to assess the relationship of these changes over a period of 2 years in men treated with triptorelin as primary therapy for advanced or locally advanced prostate cancer. METHODS: Data were collected for 2 years in accordance with routine clinical practice. Body image was assessed using the body image scale (BIS). Patient body mass index (BMI) and waist circumference were also measured. RESULTS: BIS and BMI data for both baseline and a least one post-baseline visit were available for 98 of the 145 patients enrolled. The median change in BIS score for patients assessed around 12 or 24 months after baseline and at the last observation was zero, indicating no body image deterioration in at least half of patients. Statistically significant BIS score increases were detected in assessments around 6, 12 and 18 months, but not after 2 years, indicating some patients experienced body image deterioration at some point during treatment. Changes in BMI from baseline were modest and generally not statistically significant. Waist circumference increased during the study (mean +/- standard deviation increase of 1.00 +/- 5.01 cm at the last observation). Positive correlations were determined between increases in BIS score and both BMI and waist circumference (r = 0.235 and 0.267, respectively; p = 0.020 and 0.008) at the last observation for all patients, as well as during the second year of the study. CONCLUSIONS: Most patients did not experience clinically meaningful worsening of body image perception during the study. BMI and waist circumference had a modest impact on body image during study year 2. PMID- 27398298 TI - The Clinical and Economic Impact of the V-Go(r) Disposable Insulin Delivery Device for Insulin Delivery in Patients with Poorly Controlled Diabetes at High Risk. AB - BACKGROUND: Diabetes is a chronic condition and when poorly controlled can lead to complications and death. Patients with glycated hemoglobin (A1C) measures >9 % are at significant risk for diabetes-related complications impacting the patient's quality of life and imposing higher costs on the healthcare system. A1C reductions of 1 % or greater in this population have demonstrated substantial health and economic benefits. Reducing the percent of patients at risk is an essential component of quality-care measures established for patients with diabetes. OBJECTIVE: To evaluate if switching patients prescribed subcutaneous insulin injections to V-Go for insulin delivery would impact clinical and economic parameters in patients with poorly controlled diabetes (A1C > 9 %). METHODS: The study was a retrospective analysis using data extracted from the electronic medical records database of a multicenter diabetes system. Outcome measures included mean change in A1C from baseline, the percent of patients achieving a reduction in A1C >=1 % while on V-Go therapy, and the impact to quality measures. In addition, economic analyses were conducted to assess the pharmacy budget impact and projected implication to total healthcare cost. RESULTS: Ninety-seven patients were evaluated after a mean duration of 13.6 +/- 6.9 weeks of insulin delivery with V-Go. Switching to V-Go resulted in an overall mean change (95 % CI) in A1C of -2.0 % (-1.7 to -2.3; p < 0.001) from a baseline of 10.5 %. Seventy-three percent of patients achieved an A1C reduction >=1 %. Cost analysis supported a direct pharmacy savings of $119.30 (18.80-219.60, p = 0.020) per patient per month compared with baseline. CONCLUSION: Switching to V Go for insulin delivery resulted in significant glycemic improvement and proved cost effective. This real-world assessment could be applied more broadly at the health system and plan level. PMID- 27398299 TI - Inadequate Sedation During Therapeutic Paralysis: Use of Bispectral Index in Critically Ill Patients. AB - BACKGROUND: Patients receiving therapeutic paralysis may experience inadequate sedation due to intrinsic limitations of behavioral sedation assessment. Bispectral index (BISTM) provides an objective measure of sedation; however, the role of BISTM is not well defined in intensive care unit (ICU) patients on neuromuscular blocking agents (NMBA). OBJECTIVE: The aim of this study was to delineate the relationship between BISTM and level of sedation for critically ill patients during therapeutic paralysis. METHODS: This was a retrospective observational study conducted in ICU patients receiving continuous infusion NMBA and BISTM monitoring. The primary endpoint was the correlation of BISTM <60 during therapeutic paralysis with a Richmond Agitation Sedation Score (RASS) of 4 to -5 (i.e., deep or unarousable sedation) at the time of emergence from therapeutic paralysis. RESULTS: Thirty-one patients were included in the analysis. Three of these patients (9.6 %) were inadequately sedated upon emergence from paralysis; that is, restless or agitated (RASS +1 to +2). We did not observe a correlation between BISTM and RASS upon emergence from paralysis (r = 0.27, p = 0.14). The sensitivity of BISTM <60 in predicting deep sedation (RASS -5 to -4) was 100 % (95 % confidence interval [CI] 0-100) with a positive predictive value of 35.7 %. The sensitivity and positive predictive value of BISTM <60 in predicting light sedation or deeper (RASS -5 to -2) was 92.9 % (95 %CI 83.3-100) and 92.9 %, respectively. CONCLUSION: These results suggest that 1 in 10 critically ill patients receiving therapeutic paralysis may be inadequately sedated. BISTM monitoring may serve as a useful adjunctive measure of sedation in critically ill patients receiving therapeutic paralysis. PMID- 27398301 TI - Patients' Willingness to Take Multiple-Tablet Antiretroviral Therapy Regimens for Treatment of HIV. AB - BACKGROUND: The costs of combination antiretroviral therapy (cART) for HIV, consisting of separate, particularly generic, components (multiple-tablet regimens, MTR) are generally much lower than those of single-tablet regimens (STR) comprising the same active ingredients. OBJECTIVES: To assess whether patients would be willing to take MTR, once-daily, instead of STR, with the goal of reducing general healthcare costs. In addition, we aimed to examine whether willingness was associated with particular patient characteristics. METHODS: Data from the ATHENA cohort database in The Netherlands of adult HIV-1-infected patients in care and taking cART >=6 months were used to select 1000 potential participants for an online patient survey on patient preferences and satisfaction. Participants were asked whether they would be willing to take three pills with the equivalent active ingredients simultaneously instead of STR to reduce costs. Multivariate logistic regression was used to examine associations between patient characteristics and willingness to take MTR instead of STR. RESULTS: Forty-seven percent (n = 152) of the 322 respondents answered 'yes' and 26 % (n = 83) answered 'maybe' when asked whether they would be willing to take three pills with the equivalent active ingredients simultaneously to reduce costs. Non-Dutch patients were significantly more likely to answer 'no' (OR: 2.49; 95 % CI: 1.17-5.30) or 'maybe' (OR: 2.63; 95 % CI: 1.24-5.60). Answering 'no' was less common among patients who had been taking cART >=15 years (OR: 0.23; 95 % CI: 0.09-0.58). Commonly reported concerns included the dosing frequency, efficacy and tolerability of MTR. CONCLUSIONS: HIV-infected patients do not necessarily oppose the decision to prescribe MTR instead of STR to reduce healthcare costs. However, the potential trade-off in terms of convenience should be carefully weighed against the projected savings. PMID- 27398300 TI - Systematic Adverse Drug Reaction Monitoring of Patients Under Newer Antiepileptic Drugs Using Routine Clinical Data of Inpatients. AB - BACKGROUND: Based on data of clinical trials, new agents are receiving approval to the pharmaceutical market, for which information concerning safety issues under real-life conditions is not yet available. OBJECTIVES: The aim was to evaluate the tolerability of newer antiepileptic drugs (AEDs), such as topiramate, levetiracetam, zonisamide, pregabalin, extended-release oxcarbazepine, lacosamide and eslicarbazepine, under real-life conditions by means of an assessment of routine clinical data of inpatients. METHOD: Over 2.75 years data of all inpatients receiving one of the newer AEDs were documented. Occurring adverse drug reactions (ADRs) were classified according to the WHO-UMC Causality Assessment concerning their likely relationship to the prescribed AEDs. For each AED, the total number of patients without and with ADRs, assessed as at least possibly related to the particular drug, was calculated and corresponding incidences compared with reference data provided in the Summary of Product Characteristics (SmPC). For statistical evaluation Spearman correlation (rs), estimated relative risk and logistic regression analysis were used. RESULTS: In total, the data of 562 patients were assessed, of which 90 % received up to six different AEDs. The proportion of off-label use with regard to dosage varied between 6.4 and 64.7 %. Levetiracetam and oxcarbazepine as an extended-release formulation were most commonly used, and levetiracetam showed the best tolerance. By using logistic regression, the occurrence of ADRs was significantly associated with the number of AEDs (p < 0.001) as well as the defined daily doses (p = 0.003). In total, ADRs of AEDs were documented for 318 patients (56.6 %). The most common referred to electrolyte imbalance, e.g., low sodium (n = 79, 14.1 %) and potassium (n = 25, 4.4 %) levels, the central nervous system, including dizziness (n = 61, 10.9 %), disturbed vision (n = 47, 8.4 %), fatigue (n = 40, 7.1 %), nystagmus (n = 36, 6.4 %) and ataxia (n = 29, 5.2 %), or cognitive deficits, especially disturbance of speech (n = 37, 6.6 %), memory impairment (n = 36, 6.4 %) and mental slowing (n = 32, 5.7 %). By comparing the assessed ADR incidences with specification data, for some ADRs, a probable underestimation by the SmPC of respective risk could be assumed. CONCLUSION: During inpatient treatment, valuable data are generated, which are currently rarely utilized for pharmacoepidemiologic or pharmacovigilance purposes. A systematic evaluation of these data can increase the probability of detecting ADRs and can promote real life-related drug surveillance. PMID- 27398302 TI - Accuracy of Adverse Drug Reaction Documentation upon Implementation of an Ambulatory Electronic Health Record System. AB - BACKGROUND: Detection, monitoring and treatment of adverse drug reactions (ADRs) are paramount to patient safety. The use of a comprehensive electronic health record (EHR) system has the potential to address inadequacies in ADR documentation and to facilitate ADR reporting to health agencies. However, effective methods to maintain the quality of documented ADRs within an EHR have not been well studied. OBJECTIVE: To evaluate the accuracy and effectiveness of ADR documentation transfer throughout the implementation of a comprehensive EHR system. METHODS: Retrospective analysis of ADR documentation at a tertiary care pediatric hospital between January 2013 and June 2014. ADRs documented in the newly implemented ambulatory EHR, pharmacy system and hybrid health record system were extracted. Documentation inconsistencies and processes for managing ADR documentation within the EHR were reviewed. RESULTS: A total of 115 patients with 260 unique ADRs were identified. Only 155 (60 %) of the identified ADRs were found in the ambulatory EHR system. The remaining 105 ADRs (40 %) were missing from the EHR when it was compared with the other systems. Seventy-two patients (63 %) returned for a follow-up visit, and each had their ADR documentation reviewed in the ambulatory EHR. Following the visit, 44 % of these ambulatory EHR records still included incorrect information. CONCLUSIONS: We identified discrepancies in ADR documentation within hospital systems, which need to be addressed as healthcare institutions transition to EHRs. Processes related to the transfer of ADR information into the EHR should be clearly defined. To improve the quality of ADR documentation, steps to force complete and continual ADR verification should be introduced at early stages of implementation of a new EHR, and all responsible providers should play a role. PMID- 27398303 TI - Age-dependent transcriptional and epigenomic responses to light exposure in the honey bee brain. AB - Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in-hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies (MBs), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light-induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1- and 7-day-old light-exposed honey bees with age-matched dark kept individuals. We have found a number of differentially expressed genes (DEGs), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEGs show age-related changes in the amplitude of light-induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEGs are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm, one of the DEGs affected by light exposure, and the expression of microRNA miR-932. This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation. PMID- 27398304 TI - Dual binding mode of antithyroid drug methimazole to mammalian heme peroxidases - structural determination of the lactoperoxidase-methimazole complex at 1.97 A resolution. AB - Lactoperoxidase (LPO, EC 1.11.1.7) is a member of the mammalian heme peroxidase family which also includes thyroid peroxidase (TPO). These two enzymes have a sequence homology of 76%. The structure of LPO is known but not that of TPO. In order to determine the mode of binding of antithyroid drugs to thyroid peroxidase, we have determined the crystal structure of LPO complexed with an antithyroid drug, methimazole (MMZ) at 1.97 A resolution. LPO was isolated from caprine colostrum, purified to homogeneity and crystallized with 20% poly(ethylene glycol)-3350. Crystals of LPO were soaked in a reservoir solution containing MMZ. The structure determination showed the presence of two crystallographically independent molecules in the asymmetric unit. Both molecules contained one molecule of MMZ, but with different orientations. MMZ was held tightly between the heme moiety on one side and the hydrophobic parts of the side chains of Arg255, Glu258, and Leu262 on the opposite side. The back of the cleft contained the side chains of Gln105 and His109 which also interacted with MMZ. In both orientations, MMZ had identical buried areas and formed a similar number of interactions. It appears that the molecules of MMZ can enter the substrate binding channel of LPO in two opposite orientations. But once they reach the distal heme pocket, their orientations are frozen due to equally tight packing of MMZ in both orientations. This is a novel example of an inhibitor binding to an enzyme with two orientations at the same site with nearly equal occupancies. PMID- 27398305 TI - Characterization of the autophosphorylation property of HflX, a ribosome-binding GTPase from Escherichia coli. AB - Escherichia coli HflX belongs to the widely distributed but poorly characterized HflX family of translation factor-related GTPases that is conserved from bacteria to humans. A 426-residue polypeptide that binds 50S ribosomes and has both GTPase and ATPase activities, HflX also exhibits autophosphorylation activity. We show that HflX(C), a C-terminal fragment of HflX, has an enhanced autophosphorylation activity compared to the full-length protein. Using a chemical stability assay and thin layer chromatography, we have determined that phosphorylation occurs at a serine residue. Each of the nine serine residues of HflX(C) was mutated to alanine. It was found that all but S211A retained autophosphorylation activity, suggesting that S211, located in the P-loop, was the likely site for autophosphorylation. While the S211A mutant lacked the autophosphorylation site, it possessed strong GTP binding and GTPase activities. PMID- 27398306 TI - Increased expression of kindlin-2 is correlated with hematogenous metastasis and poor prognosis in patients with clear cell renal cell carcinoma. AB - Kindlin-2 is involved in activating the integrin signaling pathway which plays an important role in regulating cancer cell invasion. However, the role of kindlin-2 may vary among cancer types. The aim of this study was to explore the possible association between kindlin-2 and clear cell renal cell carcinoma (ccRCC), and its potential role in the prognosis of ccRCC. Immunohistochemistry assays were used to examine kindlin-2 expression levels in cancer tissues obtained from 336 patients with ccRCC. The correlation between kindlin-2 expression levels and pathologic variables was then analyzed. In addition, the association between kindlin-2 expression levels and survival time was analyzed by Kaplan-Meier survival curves and log-rank tests. Of 336 ccRCC patients, 199 had high levels of kindlin-2 expression, while 137 had low kindlin-2 expression levels. Patients at a late stage of ccRCC (stage III or IV) were more likely to have high kindlin-2 expression levels than those at an early stage (stage I or II) (chi(2) = 4.72, P = 0.03). Patients with high levels of kindlin-2 expression had higher risk of hematogenous metastasis (chi(2) = 6.70, P = 0.01) than those with low levels of kindlin-2 expression. In addition, the survival time was significantly shorter for patients with high levels of kindlin-2 expression than for those with low levels of kindlin-2 expression (P = 0.001 for overall survival [OS] and P = 0.002 for disease-free survival [DFS]). Multivariate survival analysis based on the Cox proportional hazards model showed that high kindlin-2 expression levels had a hazard risk (HR) of 1.76 for OS (95% CI 1.19-2.62, P = 0.005) and an HR of 1.47 for DFS (95% CI = 1.05-2.06, P = 0.026). By comparison, lymph node metastasis had an HR of 1.48 for OS (95% CI 1.04-2.10, P = 0.029) and an HR of 1.41 for DFS (95% CI 1.04-1.93, P = 0.029). This study provided strong evidence that increased kindlin-2 expression might be involved in promoting tumor invasiveness and leading to a poor prognosis of ccRCC. PMID- 27398308 TI - Characterization of the Nqo5 subunit of bacterial complex I in the isolated state. AB - The subunits that comprise bacterial complex I (NADH:ubiquinone oxidoreductase) are also found in more complicated mitochondrial enzymes in eukaryotic organisms. Although the Nqo5 subunit is one of these conserved components and important for the formation of complex, it has been little studied. Here, we report structure analyses of isolated Nqo5 from Thermus thermophilus. Biochemical studies indicated that the C-terminal region following the 30-Kd subunit motif is disordered in the isolated state, while the remaining portion is already folded. Crystallographic studies of a trypsin-resistant fragment revealed detailed structural differences in the folded domain between the isolated and complexed states. PMID- 27398307 TI - Understanding the dynamics of monomeric, dimeric, and tetrameric alpha-synuclein structures in water. AB - Human alpha-synuclein (alphaS) is an intrinsically disordered protein associated with Parkinson's disease. Molecular mechanisms of corruptive misfolding and aggregation of alphaS resulting in the disease, as well as the structure and other properties of the corresponding oligomers are not entirely understood yet, preventing the development of efficient therapies. In this study, we investigate the folding dynamics of initially unfolded hypothetical alphaS constructs in water using all-atom molecular dynamics simulations. We also employ the novel essential collective dynamics method to analyze the results obtained from the simulations. Our comparative analysis of monomeric, dimeric, and tetrameric alphaS models reveals pronounced differences in their structure and stability, emphasizing the importance of small oligomers, particularly dimers, in the process of misfolding. PMID- 27398309 TI - Identification of protein interfaces within the multi-aminoacyl-tRNA synthetase complex: the case of lysyl-tRNA synthetase and the scaffold protein p38. AB - Human cytoplasmic lysyl-tRNA synthetase (LysRS) is associated within a multi aminoacyl-tRNA synthetase complex (MSC). Within this complex, the p38 component is the scaffold protein that binds the catalytic domain of LysRS via its N terminal region. In addition to its translational function when associated to the MSC, LysRS is also recruited in nontranslational roles after dissociation from the MSC. The balance between its MSC-associated and MSC-dissociated states is essential to regulate the functions of LysRS in cellular homeostasis. With the aim of understanding the rules that govern association of LysRS in the MSC, we analyzed the protein interfaces between LysRS and the full-length version of p38, the scaffold protein of the MSC. In a previous study, the cocrystal structure of LysRS with a N-terminal peptide of p38 was reported [Ofir-Birin Y et al. (2013) Mol Cell 49, 30-42]. In order to identify amino acid residues involved in interaction of the two proteins, the non-natural, photo-cross-linkable amino acid p-benzoyl-l-phenylalanine (Bpa) was incorporated at 27 discrete positions within the catalytic domain of LysRS. Among the 27 distinct LysRS mutants, only those with Bpa inserted in place of Lys356 or His364 were cross-linked with p38. Using mass spectrometry, we unambiguously identified the protein interface of the cross linked complex and showed that Lys356 and His364 of LysRS interact with the peptide from Pro8 to Arg26 in native p38, in agreement with the published cocrystal structure. This interface, which in LysRS is located on the opposite side of the dimer to the site of interaction with its tRNA substrate, defines the core region of the MSC. The residues identified herein in human LysRS are not conserved in yeast LysRS, an enzyme that does not associate within the MSC, and contrast with the residues proposed to be essential for LysRS:p38 association in the earlier work. PMID- 27398310 TI - Decorin-mediated inhibition of the migration of U87MG glioma cells involves activation of autophagy and suppression of TGF-beta signaling. AB - Decorin (DCN) is a major member of the small leucine-rich proteoglycan (SLRP) family that is critically involved in tumorigenesis and the development of metastasis of cancers, including glioma. Overexpression of DCN was indicated to suppress glioma cell growth. However, the role of DCN in the migration of glioma cells remain elusive. In this study, we found that treatment with exogenous DCN inhibited the adhesion and migration of U87MG glioma cells with down-regulation of TGF-beta signaling. DCN also activated autophagy, as indicated by monodansylcadaverine (MDC) staining, increase in LC3 I/LC3 II conversion, and p62/SQSTM1 degradation in U87MG cells. The increased activity of autophagy was found to be connected to the inhibition on glioma cell migration. Knockdown of DCN expression or the disruption of autophagy with 3-methyladenine (3-MA) was able to reduce the suppression on cell adhesion and migration induced by DCN. When U87MG cells were treated with temozolomide (TMZ), induction of autophagy and up-regulation of DCN were observed, accompanied by suppressed cell adhesion and migration. Transfection of siRNA targeting DCN attenuated the suppressive effect of TMZ on glioma cell migration and adhesion. Our results indicated that the migration of glioma cells was under the control of the active status of autophagy, with DCN serving as a key player, as well as an indicator of the outcome. Therefore, it is suggested that autophagy-modulating reagents could be considered for the treatment of invasive glioma. PMID- 27398311 TI - Exposure to concentrated ambient fine particulate matter disrupts vascular endothelial cell barrier function via the IL-6/HIF-1alpha signaling pathway. AB - Exposure to concentrated ambient fine particulate matter (PM2.5) has been associated with cardiovascular diseases (CVDs). The barrier function of vascular endothelial cells is critical for the development of CVDs. Here, we employed human umbilical vein endothelial cells to clarify the function of ambient PM2.5 pollution in the regulation of membrane permeability of vascular endothelial cells. The results show that a high concentration of PM2.5, which mainly includes heavy metals and polycyclic aromatic hydrocarbons, induces barrier dysfunction of vascular endothelial cells. This was mediated in part by promoting IL-6 expression, which then increases the transcriptional activity of HIF-1alpha by promoting its translocation to the nucleus. Our findings indicate that concentrated PM2.5 can destroy membrane integrity and promote permeability in vascular endothelial cells, thereby contributing to the development of CVDs. PMID- 27398312 TI - Mutations Y493G and K546D in human HSP90 disrupt binding of celastrol and reduce interaction with Cdc37. AB - Celastrol, a natural compound derived from the Chinese herb Tripterygium wilfordii Hook F, has been proven to inhibit heat shock protein 90 (HSP90) activity and has attracted much attention because of its promising effects in cancer treatment and in ameliorating degenerative neuron diseases. However, the HSP90 structure involved in celastrol interaction is not known. Here, we report a novel celastrol-binding pocket in the HSP90 dimer, predicted by molecular docking. Mutation of the two key binding pocket amino acids (Lys546 and Tyr493) disrupted the binding of celastrol to HSP90 dimers, as detected by isothermal titration calorimetry (ITC). Interestingly, such mutations also reduced binding between HSP90 and the cochaperone Cdc37, thus providing a new explanation for reported findings that celastrol shows more obvious effects in disrupting binding between HSP90 and Cdc37 than between HSP90 and other cochaperones. In short, our work discloses a novel binding pocket in HSP90 dimer for celastrol and provides an explanation as to why celastrol has a strong effect on HSP90 and Cdc37 binding. PMID- 27398313 TI - miR-132 mediates a metabolic shift in prostate cancer cells by targeting Glut1. AB - Prostate cancer is the second leading cause of cancer-related deaths among men worldwide. Early diagnosis increases survival rates in patients but the survival rate has remained relatively poor over the past years. Increasing evidence shows that altered metabolism is a critical hallmark in prostate cancer. There is a strong need to explore the molecular mechanisms underlying cancer metabolism for prostate cancer therapy. Whether the aberrant expression of microRNA (miRNA) contributes to cancer metabolism is not fully known. In this study, we found that microRNA-132 (miR-132) expression is reduced and thus leads to a metabolic switch in prostate cancer cells. miR-132 performs this role by increasing Glut1 expression, resulting in the enhanced rate of lactate production and glucose uptake. The altered metabolism induced by decreased miR-132 levels confers the rapid growth of the cancer cells. These data indicate that miR-132 is involved in regulating the Warburg effect in prostate cancer by inhibiting Glut1 expression. PMID- 27398314 TI - Platelet-to-lymphocyte ratio could be a promising prognostic biomarker for survival of colorectal cancer: a systematic review and meta-analysis. AB - Inflammation is one of the most important causes leading to colorectal carcinogenesis, and inflammatory biomarkers such as the platelet-to-lymphocyte ratio (PLR) might predict survival in colorectal cancer (CRC). However, the prognostic value of PLR in CRC patients remains controversial. The prognostic value of PLR was comprehensively analyzed in 12 articles including 3541 CRC patients (10 for overall survival (OS), seven for disease-free survival (DFS), three for recurrence-free survival (RFS), and three for cancer-specific survival (CSS)) in this study. The overall pooled hazard ratios (HRs) of PLR for OS, DFS, and CSS were significant at 1.29 (95% confidence interval, CI = 1.13-1.47, P H = 0.149), 1.43 (95% CI = 1.03-1.97, P H = 0.025), and 1.26 (95% CI = 1.04-1.52, P H = 0.223), respectively. However, there was no evidence of significance for RFS (HR = 1.29, 95% CI = 0.98-1.70, P H = 0.231) in our study. Stratified analyses indicated elevated PLR was a predictor of poor OS (metastatic patients) and DFS (Caucasian population) and was also significantly associated with OS in univariate analysis (HR = 1.35, 95% CI = 1.14-1.60, P H = 0.532) and those only treated surgically (HR = 1.37, 95% CI = 1.10-1.70, P H = 1.080). However, our findings indicated that elevated PLR is a promising prognostic biomarker for colorectal cancer, especially in metastatic Caucasian CRC patients. PMID- 27398315 TI - Characterization of group II chaperonins from an acidothermophilic archaeon Picrophilus torridus. AB - Chaperonins are a type of molecular chaperone that assist in the folding of proteins. Group II chaperonins play an important role in the proteostasis in the cytosol of archaea and eukarya. In this study, we expressed, purified, and characterized group II chaperonins from an acidothermophilic archaeon Picrophilus torridus. Two genes exist for group II chaperonins, and both of the gene products assemble to form double-ring complexes similar to other archaeal group II chaperonins. One of the Picrophilus chaperonins, PtoCPNalpha, was able to refold denatured GFP at 50 degrees C. As expected, PtoCPNalpha exhibited an ATP dependent conformational change that is observed by the change in fluorescence and diffracted X-ray tracking (DXT). In contrast, PtoCPNalpha lost its protein folding ability at moderate temperatures, becoming unable to interact with unfolded proteins. At lower temperatures, the release rate of the captured GFP from PtoCPNalpha was accelerated, and the affinity of denatured protein to PtoCPNalpha was weakened at the lower temperatures. Unexpectedly, in the DXT experiment, the fine motions were enhanced at the lower temperatures. Taken together, the results suggest that the fine tilting motions of the apical domain might correlate with the affinity of group II chaperonins for denatured proteins. PMID- 27398316 TI - Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor. AB - We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ?yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ?yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins. PMID- 27398317 TI - Identification of lung-specific genes by meta-analysis of multiple tissue RNA-seq data. AB - Lung-specific genes play critically important roles in lung development, lung physiology, and pathogenesis of lung-associated diseases. We performed a meta analysis of multiple tissue RNA-seq data to identify lung-specific genes in order to better investigate their lung-specific functions and pathological roles. We identified 83 lung-specific genes consisting of 62 protein-coding genes, five pseudogenes and 16 noncoding RNA genes. About 49.4% of lung-specific genes were implicated in the pathogenesis of lung diseases and 21.7% were involved with lung development. The identification of genes with enriched expression in the lung will facilitate the elucidation of lung-specific functions and their roles in disease pathogenesis. PMID- 27398318 TI - Aurora A kinase is required for activation of the Fanconi anemia/BRCA pathway upon DNA damage. AB - Previous studies have linked the DNA damage response to mitotic progression machinery. Mitotic kinases, such as Aurora A kinase and Polo-like kinase, are involved in the phosphorylation of cell cycle regulators in response to DNA damage. Here, we investigated the potential involvement of Aurora A kinase in the activation of the Fanconi anemia (FA)/BRCA pathway, which participates in cellular response to DNA interstrand cross-link lesions (ICL). Initially, we detected interactions between Aurora A kinase and FANCA protein, one of the components of the FA nuclear core complex. Silencing of Aurora A kinase led to inhibition of monoubiquitination of FANCD2 and formation of nuclear foci, the final consequences of FA/BRCA pathway activation upon ICL induction. An in vitro kinase assay revealed that Aurora A kinase phosphorylates S165 of FANCA. Moreover, this phosphorylation event was induced by the treatment with mitomycin C (MMC), an ICL-inducing agent. In cells overexpressing S165A mutant FANCA, monoubiquitination of FANCD2 and nuclear foci formation was impaired and cellular sensitivity to MMC was enhanced. These results suggest that S165 phosphorylation by Aurora A kinase is required for proper activation of the FA/BRCA pathway in response to DNA damage. PMID- 27398319 TI - Uptake and Usage of IntelliCare: A Publicly Available Suite of Mental Health and Well-Being Apps. AB - BACKGROUND: Treatments for depression and anxiety have several behavioral and psychological targets and rely on varied strategies. Digital mental health treatments often employ feature-rich approaches addressing several targets and strategies. These treatments, often optimized for desktop computer use, are at odds with the ways people use smartphone applications. Smartphone use tends to focus on singular functions with easy navigation to desired tools. The IntelliCare suite of apps was developed to address the discrepancy between need for diverse behavioral strategies and constraints imposed by typical app use. Each app focuses on one strategy for a limited subset of clinical aims all pertinent to depression and anxiety. This study presents the uptake and usage of apps from the IntelliCare suite following an open deployment on a large app marketplace. METHODS: Thirteen lightweight apps, including 12 interactive apps and one Hub app that coordinates use across those interactive apps, were developed and made free to download on the Google Play store. De-identified app usage data from the first year of IntelliCare suite deployment were analyzed for this study. RESULTS: In the first year of public availability, 5,210 individuals downloaded one or more of the IntelliCare apps, for a total of 10,131 downloads. Nearly a third of these individuals (31.8%) downloaded more than one of these apps. The modal number of launches for each of the apps was 1, however the mean number of app launches per app ranged from 3.10 to 16.98, reflecting considerable variability in the use of each app. CONCLUSIONS: The use rate of the IntelliCare suite of apps is higher than public deployments of other comparable digital resources. Our findings suggest that people will use multiple apps and provides support for the concept of app suites as a useful strategy for providing diverse behavioral strategies. PMID- 27398320 TI - Skin and Neourethral Necrosis in Staged Hypospadias Repair. AB - Complications in hypospadias surgery are not uncommon however penile skin or flap necrosis is rarely reported. Ischemia of the flap or graft is a major complication in two stage repair of hypospadias. A 2-year old boy with proximal penile hypospadias, operated earlier for chordee correction and urethral plate formation with a preputial flap, presented for stage 2 repair. Ten days after surgery patient developed skin and neourethral necrosis. Early debridement was done followed by coverage with scrotal flaps. PMID- 27398321 TI - Ewing's Sarcoma of the Adrenal Gland. AB - Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery. PMID- 27398322 TI - Malignant Myopericytoma of Shoulder: A Rare Lesion. AB - Myopericytoma is a soft tissue tumor with perivascular myoid differentiation. It accounts for 1% of the vascular tumors and involves mostly cutaneous or subcutaneous tissue of the limbs in adults. Malignant myopericytoma is exceedingly rare. A 15-year old girl presented with slowly progressive mass over left shoulder region. Histopathology and immunohistochemistry after complete excision revealed it as malignant myopericytoma. PMID- 27398323 TI - Sacrococcygeal Teratoma associated with Trisomy 13. AB - Sacrococcygeal teratoma (SCT) is rarely associated with syndromes. We report a female newborn with a prenatal diagnosis of small sacrococcygeal teratoma and postnatally diagnosed as having trisomy 13. The sacrococcygeal teratoma was excised. It was reported as mature teratoma. The child succumbed to sepsis postoperatively. PMID- 27398324 TI - Infantile Fibrosarcoma of Tongue: A Rare Tumor. AB - Infantile fibrosarcoma is very rare tumor and seldom occurs in oral cavity. Overall good prognosis is reported in more than 80% cases. We present a 5-month old female patient with swelling of the tongue for four months. This was excised completely. Histopathology and immunohistochemistry revealed it as infantile fibrosarcoma of grade II. PMID- 27398325 TI - Preduodenal Portal Vein with Situs Inversus Totalis causing Duodenal Obstruction. AB - Congenital duodenal obstruction sometimes may be secondary to unusual entities like preduodenal portal vein (PDPV) the identification of which is very important to avoid inadvertent injury or incorrect surgery. A 6-day old neonate presented with congenital duodenal obstruction. Investigations revealed situs inversus totalis with many congenital cardiovascular anomalies. At operation preduodenal portal vein and malrotation were found. Correction of malrotation and bypass duodeno-duodenostomy were done. PMID- 27398326 TI - Intestinal Perforation in Obstructed Umbilical Hernia due to Wedged Plum Seed. AB - The foreign body ingestion is a rare cause of gastrointestinal perforation in children and is typically seen with sharp foreign bodies or button batteries. Herein, we report an 11-month old male baby who presented with obstructed umbilical hernia. Abdominal radiograph showed dilated small bowel loops, while ultrasonography and CT scan suggested presence of a foreign body. Laparotomy revealed obstructed umbilical hernia with a plum seed being stuck in the terminal ileum causing intestinal perforation. Resection and anastomosis of intestine was performed. PMID- 27398327 TI - Sacrococcygeal Teratoma: Mistreated With Repeated Aspirations. PMID- 27398329 TI - Sex Differences in Fear of Falling among Older Adults with Low Grip Strength. AB - BACKGROUND: Fear of falling is not only a risk factor for falls, but it is also an important clinical predictor of functional decline in older adults. This study identified sex differences in fear of falling and related factors in older adults with low grip strength. METHODS: The data of 902 older adults from the 2012 Korean National Survey, conducted as a research project by the Korea Employment Information Service, were analyzed. Grip strength, activities of daily living, cognitive function, depressive symptoms, and fear of falling were assessed. Multiple regression analysis was performed by a simultaneous data entry method. RESULTS: Fear of falling was greater in older women with low grip strength than in their male equivalents (P<0.001). Regression analysis showed that age, fall experience within the previous 2 yr, activities of daily living, and depressive symptoms collectively accounted for 15.3% (P<0.001) of the variance among men. Meanwhile, age, fall experience within the previous 2 yr, grip strength, activities of daily living, and depressive symptoms collectively accounted for 13.4% (P<0.001) of the variance among women. CONCLUSION: Thus, the predictors of fear of falling differ between older men and women with low grip strength. Therefore, sex differences must be considered when developing intervention strategies for reducing fear of falling in this demographic. PMID- 27398330 TI - Berberine Induced Apoptosis of Human Osteosarcoma Cells by Inhibiting Phosphoinositide 3 Kinase/Protein Kinase B (PI3K/Akt) Signal Pathway Activation. AB - BACKGROUND: Osteosarcoma is a malignant tumor with high mortality but effective therapy has not yet been developed. Berberine, an isoquinoline alkaloid component in several Chinese herbs including Huanglian, has been shown to induce growth inhibition and the apoptosis of certain cancer cells. The aim of this study was to determine the role of berberine on human osteosarcoma cell lines U2OS and its potential mechanism. METHODS: The proliferation effect of U20S was exanimed by 3 (4,5)-dimethylthiahiazo(-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and the percentage of apoptotic cells were determined by flow cytometric analysis. The expression of PI3K, p-Akt, Bax, Bcl-2, cleavage-PARP and Caspase3 were detected by Western blott. RESULTS: Berberine treatment caused dose-dependent inhibiting proliferation and inducing apoptosis of U20S cell. Mechanistically, berberine inhibits PI3K/AKT activation that, in turn, results in up-regulating the expression of Bax, and PARP and down-regulating the expression of Bcl-2 and caspase3. In all, berberine can suppress the proliferation and induce the apoptosis of U2OS cell through inhibiting the PI3K/Akt signaling pathway activation. CONCLUSION: Berberine can suppress the proliferation and induce the apoptosis of U2OS cell through inhibiting the PI3K/Akt signaling pathway activation. PMID- 27398328 TI - Hyperbilirubinemia in Neonates: Types, Causes, Clinical Examinations, Preventive Measures and Treatments: A Narrative Review Article. AB - BACKGROUND: Hyperbilirubinemia, or jaundice, is a life threatening disorder in newborns. It is a multifactorial disorder with many symptoms. Generally, the physiological jaundice is the most prevalent type however in some regions pathological jaundice is also common. This review article focuses on a brief introduction to jaundice, its types and causes, measuring the bilirubin level, clinical approaches towards hyperbilirubinemia, different precautionary measures for the parents of babies suffering from hyperbilirubinemia and different remedial therapeutic measures for its treatment. METHODS: The main databases including Scopus, Pubmed, MEDLINE, Google scholar and Science Direct were researched to obtain the original papers related to the newborns' hyperbilirubinemia. The main terms used to literature search were "newborns' hyperbilirubinemia", "newborns' jaundice", "Physiological Jaundice" and "Patholigical Jaundice". The timeframe included the obtained articles was from 1952 to 2015. RESULTS: Neonatal jaundice due to breast milk feeding is also sometimes observed. Hemolytic jaundice occurs because of the incompatibility of blood groups with ABO and Rh factors, when the fetus and mother blood groups are not compatible and the fetus blood crosses the barrier of the umbilical cord before birth causing fetus blood hemolysis owing to severe immune response. CONCLUSION: Jaundice is easily diagnosable however require quick and on the spot treatment. If not treated properly, it leads to many complications. Currently the treatment options for jaundice include photo therapy, chemotherapy, and vaccinations. PMID- 27398331 TI - Why Women Are Averse to Facility Delivery in Northwest Nigeria: A Qualitative Inquiry. AB - BACKGROUND: In many sub-Saharan African countries the rate of antenatal care (ANC) has been increased but skilled birth attendance rate is still low. The objective of this study was to evaluate the reasons why women prefer home delivery when facility based delivery is available at minimal cost. METHODS: This study was conducted in Northwest Nigeria using a qualitative method (phenomenology) among five categories of women in April - May 2013. This study investigated different categories of women (those that never attend ANC nor deliver in the facility, those that attend ANC but delivered at home and those that delivered once in the facility but fail to return in subsequent deliveries, the in-laws and facilities staff). RESULTS: Through focus group discussions and In-depth interviews several reasons why women are averse to hospital deliveries were identified. Women reported ignorance, abuse, illiteracy, and poverty, and low esteem, poor attitude of health workers, few working hours and some integrated health services like preventing mother to child transmission of HIV testing as deterrents, while cheap and accessible services were reasons for preference to traditional birth attendants. CONCLUSIONS: The findings highlighted important entrenched barriers to facility deliveries among women, which is basically socio-cultural and economic. Therefore emphasis must be given to health education program to ensure comprehensive and target specific messages that will address individual needs of the groups. PMID- 27398333 TI - Sexual and Drug Use Risk Behaviors of Internal Long Distance Truck Drivers in Iran. AB - BACKGROUND: Long Distance Truck Drivers (LDTDs) and their sexual health risk behaviors have been associated with greater prevalence of sexually transmitted Infections (STIs), HIV and hepatitis virus transmission. However, there is no information about Iranian LDTDs' high-risk behaviors. The aim of this investigation was to estimate the prevalence of high-risk behaviors in Iranian LDTDs. METHODS: This cross-sectional study was conducted in Jun 2014 with LDTDs from Tehran Province of Iran. LDTDs were recruited via convenience sampling and given a 43-item reliable and valid questionnaire to assess sexual health risk behaviors and demographic and background characteristics of study participants. RESULTS: A total of 349 LDTDs with the mean age of 36.91 yr (range, 19-65 yr) participated in the study. The average duration of staying away from home for participants was 5 d (SD=+/-1). Majority of the LDTDs were married (82.2 %) and had more than 5 yr (inclusive) of formal education (95.7%). Younger LDTDs reported more condom use with their partners (r=-0.170, P<=0.001), more extramarital sexual contacts (r=-0.157, P<=0.001), more pay for sex (r=-0.110, P<=0.005) and condom use in their extra-marital sex contacts (including with sex workers) (r=-0.176, P<=0.001). CONCLUSION: Iranian LDTDs have specific risk factors for unhealthy sexual behaviors. Prevention efforts must emphasize on specific high-risk groups. PMID- 27398334 TI - Spatial Analysis of China Province-level Perinatal Mortality. AB - BACKGROUND: Using spatial analysis tools to determine the spatial patterns of China province-level perinatal mortality and using spatial econometric model to examine the impacts of health care resources and different socio-economic factors on perinatal mortality. METHODS: The Global Moran's I index is used to examine whether the spatial autocorrelation exists in selected regions and Moran's I scatter plot to examine the spatial clustering among regions. Spatial econometric models are used to investigate the spatial relationships between perinatal mortality and contributing factors. RESULTS: The overall Moran's I index indicates that perinatal mortality displays positive spatial autocorrelation. Moran's I scatter plot analysis implies that there is a significant clustering of mortality in both high-rate regions and low-rate regions. The spatial econometric models analyses confirm the existence of a direct link between perinatal mortality and health care resources, socio-economic factors. CONCLUSIONS: Since a positive spatial autocorrelation has been detected in China province-level perinatal mortality, the upgrading of regional economic development and medical service level will affect the mortality not only in region itself but also its adjacent regions. PMID- 27398332 TI - Lower Serum Levels of Uric Acid in Uterine Fibroids and Fibrocystic Breast Disease Patients in Dongying City, China. AB - BACKGROUND: Increasing serum levels of uric acid (SUA) after menopause in women brought up a hypothesis that estrogenic effect may protectively regulate SUA. Estrogenic effect is a major etiology of uterine fibroids and fibrocystic breast disease. The study aimed to explore SUA among patients suffering from these diseases to enhance the hypothesis. METHODS: Overall, 1349 female participants were selected into three cases: Case I having uterine fibroids (n=568), Case II having fibrocycstic breast disease (n=608) and Case III having uterine fibroids combining with fibrocycstic breast disease (n=173); 4206 participants without these diseases were selected as controls. Based on health check-up data from 2011 to 2012, in Dongying Shengli Oilfield Central Hospital, a cross-sectional study was conducted to examine the difference in SUA between the case and control. We adjusted covariates by generalized linear regression mode. RESULTS: From 19 to 44 yr, SUA of Case I to Case III were lower than controls by 8.46 umol/L (P=0.011), 5.88umol/L (P=0.014) and 9.39 umol/L (P=0.059), respectively. From 45-54 yr, no significant differences were between three cases and controls. In Case I and its control: from 54-59 yr, differences were not significant; from 60 to 72 yr, SUA in Case I was lower than the control by 32.02umol/L (P=0.003). CONCLUSION: Participants of uterine fibroids and fibrocystic breast disease had a lower SUA except the stage of menopause, which indirectly supported that estrogenic effect, may protectively decrease SUA. PMID- 27398335 TI - Psychiatric Disorders Are Associated with an Increased Risk of Injuries: Data from the Iranian Mental Health Survey (IranMHS). AB - BACKGROUND: Injuries and psychiatric disorders, notably both major public health concerns, are associated with a high burden and are believed to be bi directionally correlated. Those inflicted with injuries face increased risks of mental illnesses. Psychiatric disorders may make the individual prone to injuries. The objective of the study was to assess the correlation of mental disorders with non-fatal injuries. METHODS: A total of 7886 participants aged 15 to 64 yr were interviewed in a national household survey in 2011 in Iran. Composite International Diagnostic Interview (CIDI v2.1) was implemented to assess the prevalence of psychiatric disorders in the past twelve months. Injuries were assessed using Short Form Injury Questionnaire (SFIQ-7). RESULTS: Injury was reported in 35.9% and 22.8% of participants in the past twelve and past three months, respectively. Using multivariate logistic regression analysis, mental disorders were significantly associated with injuries in the past three months (OR=1.6, 95% CI:1.36-1.87), recurrent injuries (OR=1.7, 95% CI: 1.21-2.41) and road/traffic accidents (OR=2.4, 95% CI: 1.28-4.49). CONCLUSION: Psychiatric disorders were found to be associated with an increased risk of injuries. Early detection and treatment of mental illnesses can contribute to injury prevention. PMID- 27398336 TI - Effect of Daylight on Melatonin and Subjective General Health Factors in Elderly People. AB - BACKGROUND: This paper investigated the effect of daylight on morning and night melatonin, subjective general health using GHQ questionnaire, sleepiness and alertness on elderly who lived in nursing houses. METHODS: Nineteen nursing home residents participated voluntarily. They exposed to daylight from 9 to 10 a.m. and from 4 to 5 p.m. for 6 wk. The level of melatonin in the morning and at night was measured. General health of all participants was evaluated using General Health Questionnaire (GHQ) as well. RESULTS: Daylight exposure significantly affected morning melatonin from 25.39 pg/ml to 59.77 pg/ml (P=0.001) and night melatonin were changed from 40.30pg/ml to 34.41pg/ml (P=0.081). Mean score of general health changed 36.31 to 29.89 (P=0.003). Karolinska Sleepiness Scale (KSS) and Visual Analogue Scale (VAS) showed increase sleepiness and decrease alertness from 3:00 to 7:00 a.m. Sleepiness decreased and alertness increased during 1:00 p.m. and 20:00 p.m. CONCLUSIONS: Daylight exposure could delay sleep phase and correction of circadian rhythm in elderly. Anxiety and insomnia could be improved with daylight exposure. It suggests that elders should be exposed to scheduled daylight in morning and evening for prevention and improvement of mental disorders. Adequate light should be provided for elder's homes and nursing house. PMID- 27398337 TI - TIM-3 Rs10515746 (A/C) and Rs10053538 (C/A) Gene Polymorphisms and Risk of Multiple Sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by auto-reactive T cells against myelin antigens. T cell immunoglobulin mucin -3 (TIM-3) is a negative regulator glycoprotein expressed by a range of immune cells, including, Th1 cells, activated CD8+ T cells and in a lower level on Th17 cells. A defect in TIM-3 regulation has been shown in multiple sclerosis patients. In humans, several single nucleotide polymorphisms (SNPs) have been identified in the TIM-3 gene and are associated with inflammatory diseases. The aim of this study was to analyze the association between TIM-3 -574A>C and -1516 C>A SNPs in the promoter region, and susceptibility to MS. METHODS: DNA samples from 102 patients and 102 healthy controls were genotyped using RFLP-PCR method. RESULTS: In this case-control study, analysis of the alleles and genotypes revealed a significant higher frequency of C/C and lower frequency of A/C genotypes for -574 locus of TIM-3 gene in MS patients (P=0.0002). We also found that C/C genotype for locus of 1516 increased in MS patients, while A/C genotype decreased (P=0.012). Allele C of -574C/C and -1516 C>A SNPs were also more frequent in MS patients (P=0.036 and 0.0027 respectively). CONCLUSION: -574 A>C and -1516 C>A SNPs in the promoter region of TIM3 gene may affect the disease susceptibility. PMID- 27398338 TI - Evaluation of Bacteriological and Chemical Quality of Dialysis Water and Fluid in Isfahan, Central Iran. AB - BACKGROUND: Chemical and microbial quality of water used in hemodialysis play key roles in a number of dialysis-related complications. In order to avoid the complications and to guarantee safety and health of patients therefore, vigorous control of water quality is essential. The objective of present study was to investigate the chemical and bacteriological characteristics of water used in dialysis centers of five hospitals in Isfahan, central Iran. METHODS: A total of 30 water samples from the input of dialysis purification system and dialysis water were analyzed for chemical parameters. Heterotrophic plate count and endotoxin concentration of drinking water, dialysis water and dialysis fluid of 40 machines were also monitored over a 5-month period in 2011-2012. RESULTS: Concentration of the determined chemicals (copper, zinc, sulfate, fluoride, chloramines and free chlorine) did not exceed the recommended concentration by the Association for the Advancement of Medical Instrumentation (AAMI) exclude lead, nitrate, aluminum and calcium. Furthermore, the magnesium; cadmium and chromium concentration exceeded the maximum level in some centers. No contamination with heterotrophic bacteria was observed in all samples, while the AMMI standard for endotoxin level in dialysis fluid (<2 EU/ml) was achieved in 95% of samples. CONCLUSION: Dialysis water and fluid failed to meet the all chemical and bacteriological requirements for hemodialysis. To minimize the risk of contaminants for hemodialysis patients therefore, a water quality management program including monitoring, maintenance and development of water treatment system in hemodialysis centers is extremely important. In addition, an appropriate disinfection program is needed to guarantee better control of bacterial growth and biofilm formation. PMID- 27398339 TI - A Model for Diagnosing Breast Cancerous Tissue from Thermal Images Using Active Contour and Lyapunov Exponent. AB - BACKGROUND: The segmentation of cancerous areas in breast images is important for the early detection of disease. Thermal imaging has advantages, such as being non invasive, non-radiation, passive, quick, painless, inexpensive, and non-contact. Imaging technique is the focus of this research. METHODS: The proposed model in this paper is a combination of surf and corners that are very resistant. Obtained features are resistant to changes in rotation and revolution then with the help of active contours, this feature has been used for segmenting cancerous areas. RESULTS: Comparing the obtained results from the proposed method and mammogram show that proposed method is Accurate and appropriate. Benign and malignance of segmented areas are detected by Lyapunov exponent. Values obtained include TP=91.31%, FN=8.69%, FP=7.26%. CONCLUSION: The proposed method can classify those abnormally segmented areas of the breast, to the Benign and malignant cancer. PMID- 27398340 TI - Bioremediation of Crude Oil Using Bacterium from the Coastal Sediments of Kish Island, Iran. AB - BACKGROUND: Much of the environment is affected by petroleum contamination. It imposes serious health problems for humans as well as serious environmental impact. Bioremediation is an important consideration for removing environmental pollutants because, compared with other technologies, it incurrs lower costs and is environmentally compatible. METHODS: Crude oil degrading bacteria were isolated using serial dilutions of a bacterial consortium. The Taguchi experimental design L16 (4(5)) was used to optimize the biodegradation process of crude oil by the isolated strain. This investigation applied the parameters of temperature, salinity, pH, NH4Cl and FeSO4.7H2O. Modeling the kinetics of crude oil biodegradation included five batch cultivation experiments (2.5 ml/L to 40 ml/L) using crude oil as a single limiting substrate. RESULTS: Halomonas sp. MS1 was identified using identification tests. Maximum biodegradation efficiency was predicted to occur at pH=9, temperature=30 degrees C, salinity=2%, NH4Cl concentration=0.4 g/L and FeSO4.7H2O=0.04 g/L. After optimization, biodagradation was significantly (P<0.05) higher (i.e. 90.65%) than it results under the original conditions. Furthermore, growth kinetics modelling of bacteria in various concentrations of crude oil showed a positive correlation between increased concentration, up to 10 ml/L and bacterial growth, but this was not evident at higher concentrations (20-40 mL/L). CONCLUSION: Overall, bacteria in surface sediment samples from Kish Island have been determined as having good potential for application in oil biodegradation. Optimum amounts of the studied factors were determined successfully by applying the Taguchi experimental design and the models of Teissier and Haldane are suggested as kinetic models to describe the batch crude oil degradation behavior of MS1. PMID- 27398341 TI - Genetic Linkage Analysis of DFNB3, DFNB9 and DFNB21 Loci in GJB2 Negative Families with Autosomal Recessive Non-syndromic Hearing Loss. AB - BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common hereditary form of deafness, and exhibits a great deal of genetic heterogeneity. So far, more than seventy various DFNB loci have been mapped for ARNSHL by linkage analysis. The contribution of three common DFNB loci including DFNB3, DFNB9, DFNB21 and gap junction beta-2 (GJB2) gene mutations in ARNSHL was investigated in south of Iran for the first time. METHODS: In this descriptive study, we investigated sixteen large families with at least two affected individuals. After DNA extraction, GJB2 gene mutations were analyzed using direct sequencing method. Negative samples for GJB2 gene mutations were analyzed for the linkage to DFNB3, DFNB9 and DFNB21 loci by genotyping the corresponding short tandem repeat (STR) markers using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) methods. RESULTS: GJB2 mutations (283G>A and 29delT) were causes of hearing loss in 12.5% of families with ARNSHL and no evidence of linkage were found for any of DFNB3, DFNB9 and DFNB21 loci. CONCLUSION: GJB2 mutations are associated with ARNSHL. We failed to find linkage of the DFNB3, DFNB9 and DFNB21 loci among GJB2 negative families. Therefore, further studies on large-scale population and other loci will be needed to find conclusively linkage of DFNB loci and ARNSHL in the future. PMID- 27398342 TI - On the Ethics of Medical Tourism: An Examination of Patients' Perspectives. PMID- 27398343 TI - The Level of Stigmatization and Depression of Patients with Psoriasis. PMID- 27398344 TI - Insight into Provider Payment Mechanisms in Healthcare Industry: A Case of Iran. PMID- 27398345 TI - The Importance of Forest Fruits Consumption through View of Vitamin and Provitamin Content. PMID- 27398346 TI - The Relationship between Socio-demographic and Lifestyle Factors and Academic Performance. PMID- 27398347 TI - Do South African Children Actively Commute to School? PMID- 27398348 TI - Variations in Physical Activity of Male and Female Students from Different Countries. PMID- 27398349 TI - The Health Belief Model's Impacts on the Use of Complementary and Alternative Medicine by Parents or Guardians of Children with Cancer. PMID- 27398350 TI - Illness Perceptions and Disability Levels among Older Adults with Chronic Illness. PMID- 27398351 TI - Improving Medical Error Reporting: A Successful Experience from Iran. PMID- 27398352 TI - Concordance between self-reported body mass index with weight perception, self rated health and appearance satisfaction in people living in Tehran. AB - BACKGROUND: Obesity is investigated as a health concern due to high prevalence in the world. Nowadays, researchers are looking for an indirect method to measure weight and height. Self-reported Body Mass Index (BMI) is ever more served as an alternative method for direct weight and height measurement. Misreporting is a usual concern in self-reported BMI, thus, this study set explored the association and degree of agreement of self-reported BMI with weight perception, Self-Rated Health (SRH), and appearance satisfaction in people living in Tehran, Iran. METHODS: 722 men and women (268 men and 454 women) aged 30-64 years were selected using Cluster Multi-stage Sampling with the Probability Proportional to Size (PPS) method from each area. The questionnaire included demographic and socioeconomic variables and self-reported weight and height and questions related to weight and health perception, and appearance satisfaction. Independent samples T-test compared the mean of scales and differences in characteristics between BMI categories, analyzed using chi-square test. The Cohen's kappa coefficient examined the association between self-reported BMI and weight perception, SRH, and appearance satisfaction. RESULTS: The mean self-reported weight was 80.79 +/- 12.87 in men and 68.33 +/- 11.53 in women. The results of the agreement analysis for weight perception were Kappa = 0.38 with p < 0.0001 for women and Kappa = 0.23 with p <0.0001 for men. This measure of agreement, while statistically significant, is fair agreement. SRH and appearance satisfaction were not significantly correlated with self-reported BMI. CONCLUSION: The measurements of height and weight can cause significant imprecisions in calculation of BMI, which is used as a guide for identifying persons at risk of disease. Direct measurement of height and weight should be performed whenever possible for optimal measurements in clinical practice and clinically oriented researches. PMID- 27398353 TI - A patient-centered analysis of enrollment and retention in a randomized behavioral trial of two cognitive rehabilitation interventions for Mild Cognitive Impairment. AB - BACKGROUND: A major potential barrier for studying behavioral interventions for patients with Mild Cognitive Impairment (MCI) is the willingness and ability of people to enroll in and adhere to behavioral interventions, especially when the intervention involves dyads of patients with MCI and support partners. Details regarding recruitment strategies and processes (such as number of dyads screened) are often missing from reports of behavioral trials. In addition, reports do not detail the reasons a potentially eligible candidate opts out of participation in a research study. OBJECTIVE: To describe the challenges and successes of enrollment and retention in a behavioral trial for persons with MCI and their care partners, and to better understand barriers to participation from the patient's point of view. DESIGN: Multi-site, randomized trial. SETTING: Major medical centers. PARTICIPANTS: Our accrual target for the study was 60 participants. Potential candidates were patients presenting to memory evaluation clinics whose resulting clinical diagnosis was MCI. A total of 200 consecutive potential candidates were approached about participating in the study across the three sites. INTERVENTION: Detailed recruitment and retention data of a randomized trial comparing two behavioral interventions (memory notebook training versus computer training) provided in two separate training time frames (10 days versus 6 weeks). MEASUREMENTS: Structured interview with those declining to participate in the trial. RESULTS: Overall recruitment 37% with a range of 13% 72% across sites. Overall retention 86% with a range of 74%-94% across sites. CONCLUSION: The primary barriers to enrollment from the patient's perspective were distance to the treatment center and competing comprehensive behavioral programming. However, retention data suggest that those dyads who enroll in behavioral programs are highly committed. PMID- 27398354 TI - Variations in male-female infant ratios among births to Canadian- and Indian-born mothers, 1990-2011: a population-based register study. AB - BACKGROUND: We assessed variations in the male-female infant ratios among births to Canadian-born and Indian-born mothers according to year of birth, province and country of birth of each parent. METHODS: In this population-based register study, we analyzed birth certificates of 5 853 970 singleton live births to Canadian-born and 177 990 singleton live births to Indian-born mothers giving birth in Canada from 1990 to 2011. Male-female ratios were stratified by live birth order and plotted by year of birth. Logistic regression was used to assess whether ratios varied between Canadian provinces and according to the birthplace of each parent. The deficit in the number of girls was estimated using bootstrap methods. RESULTS: Among Canadian-born mothers, male-female ratios were about 1.05, with negligible fluctuations by birth order, year and province. Among Indian-born mothers, the overall male-female ratio at the third birth was 1.38 (95% confidence interval [CI] 1.34-1.41) and was 1.66 (95% CI 1.56-1.76) at the fourth or higher-order births. There was little variability in the ratios between provinces. Couples involving at least 1 Indian-born parent had higher than expected male-female ratios at the second and higher-order births, particularly when the father was Indian-born. The deficit in the expected number of girls among Indian immigrants to Canada in the study period was estimated to be 4472 (95% CI 3211-5921). INTERPRETATION: Fewer than expected girls at the third and higher-order births have been born to Indian immigrants across Canada since 1990. This trend was also seen among couples of mixed nativity, including those involving a Canadian-born mother and an Indian-born father. Fathers should be considered when investigating sex ratios at birth. PMID- 27398355 TI - Current use of routinely collected health data to complement randomized controlled trials: a meta-epidemiological survey. AB - BACKGROUND: Studies that use routinely collected health data (RCD studies) are advocated to complement evidence from randomized controlled trials (RCTs) for comparative effectiveness research and to inform health care decisions when RCTs would be unfeasible. We aimed to evaluate the current use of routinely collected health data to complement RCT evidence. METHODS: We searched PubMed for RCD studies published to 2010 that evaluated the comparative effectiveness of medical treatments on mortality using propensity scores. We identified RCTs of the same treatment comparisons and evaluated how frequently the RCD studies analyzed treatments that had not been compared previously in randomized trials. When RCTs did exist, we noted the claimed motivations for each RCD study. We also analyzed the citation impact of the RCD studies. RESULTS: Of 337 eligible RCD studies identified, 231 (68.5%) analyzed treatments that had already been compared in RCTs. The study investigators rarely claimed that it would be unethical (6/337) or difficult (18/337) to perform RCTs on the same question. Evidence from RCTs was mentioned or cited by authors of 213 RCD studies. The most common motivations for conducting the RCD studies were alleged limited generalizability of trial results to the "real world" (37.6%), evaluation of specific outcomes (31.9%) or specific populations (23.5%), and inconclusive or inconsistent evidence from randomized trials (25.8%). Studies evaluating "real world" effects had the lowest citation impact. INTERPRETATION: Most of the RCD studies we identified explored comparative treatment effects that had already been investigated in RCTs. The objective of such studies needs to shift more toward answering pivotal questions that are not supported by trial evidence or for which RCTs would be unfeasible. PMID- 27398356 TI - Resources and population served: a description of the Ontario Paediatric Diabetes Network. AB - BACKGROUND: The Network of Ontario Pediatric Diabetes Programs was established in 2001 to provide access to specialized pediatric diabetes care. Universal funding for pediatric insulin pump therapy has been available in Ontario since 2006. The objective of this study was to describe the distribution of patients, resources and insulin pump use across centres within the network, now called the Ontario Paediatric Diabetes Network. METHODS: We conducted a cross-sectional survey in 2012 of the 35 pediatric diabetes centres in Ontario to measure centre characteristics, patient volume and available clinical and social resources. We used health administrative data from the provincial Assistive Devices Program to describe patients aged 18 years or less using insulin pumps by centre as a measure of technology uptake. RESULTS: All 35 centres participated, reporting a total of 6676 children with type 1 diabetes and 368 with type 2 diabetes. Most (> 80%) children with type 1 diabetes were followed at tertiary (n = 5) or large community (n = 14) centres. Nursing patient load was similar between centre types, but there was a large range across centres within any type. Overall, percent insulin pump use was 38.1% and varied widely across centres (5.3%-66.7%). Funded 24-hour support for pump users was available at 5 (36%) small community centres, 3 (19%) large community centres and 2 (40%) tertiary centres. INTERPRETATION: Our study showed differences in access to specialized and after hours care for children with diabetes in Ontario. Pump use varied widely across centres. Further research is needed to assess the impact of these observed differences on quality of care and outcomes. PMID- 27398357 TI - Medical student career choice: a qualitative study of fourth-year medical students at Memorial University, Newfoundland. AB - BACKGROUND: Specialty career choice is a critical decision for medical students, and research has examined factors influencing particular specialties or assessed it from a demographic perspective. The purpose of this study was to explore and describe influential factors in students' decision-making, irrespective of their particular specialty in a Canadian medical school. METHODS: Study participants were recruited from fourth-year medical classes at the Memorial University of Newfoundland in 2003, 2006, 2007 and 2008. Sixteen focus groups (n = 70) were led by a nonfaculty facilitator to uncover factors affecting medical student career choice. The analysis was guided by principles of grounded theory methodology. The focus group transcripts were sequentially coded based on recurring topics and themes that arose in the students' discussions. A set of key themes emerged and representative quotations for each theme were tracked. RESULTS: Twenty themes were identified from the focus group discussions: 7 major, 3 intermediate and 10 minor themes. The major themes were undergraduate experience, exposure, public perception and recruitment, teacher influence, family/outside influences, residency issues and personal philosophy. Intermediate themes included lifestyle, bad-mouthing/negative perceptions and context. Minor themes included critical incidents/experiences, information gaps, uncertainty, nature of the work, extracurricular programs, timing of decision-making, financial issues, prestige, fit with colleagues and gender issues. INTERPRETATION: Exposure to specialties and the timing of this exposure appears to be crucial to career choice, as does the context (who, what, when, where) of any particular rotation. Given the influence of personal philosophy, future research examining students' level of self-assessment and self-reflection in their decision-making processes and level of certainty about their selected specialty would be useful. PMID- 27398358 TI - Mortality over 12 years of follow-up in people admitted to provincial custody in Ontario: a retrospective cohort study. AB - BACKGROUND: We aimed to define rates and causes of death in custody and after release in people admitted to provincial custody in Ontario, and to compare these data with data for the general population. METHODS: We linked data on adults admitted to provincial custody in Ontario in 2000 with data on deaths between 2000 and 2012. We examined rates and causes of death by age, sex, custodial status and period after release, and compared them with data for the general population, using indirect adjustment for age. RESULTS: Between 2000 and 2012, 8.6% (95% confidence interval [CI] 8.3%-8.8%) of those incarcerated died in provincial custody or after release. The crude death rate was 7.1 (95% CI 6.9 7.3) per 1000 person-years. The standardized mortality ratio for those incarcerated in 2000 was 4.0 (95% CI 3.9-4.1) overall and 1.9 (95% CI 1.5-2.4) while in provincial custody. The most common causes of death were injury and poisoning (38.2% of all deaths), including overdose (13.6%) and suicide (8.2%), diseases of the circulatory system (15.8%) and neoplasms (14.5%). In the 2 weeks after release, the standardized mortality ratio was 5.7 overall and 56.0 for overdose. Life expectancy was 72.3 years for women and 73.4 for men who experienced incarceration in 2000. INTERPRETATION: Mortality was high for people who experienced incarceration, and life expectancy was 4.2 years less for men and 10.6 years less for women compared with the general population. Efforts should be made to reduce the gap in mortality between people who experience incarceration and those who do not. Time in custody could serve as an opportunity to intervene to decrease risk. PMID- 27398359 TI - Hospital stays for hepatitis B or C virus infection or primary liver cancer among immigrants: a census-linked population-based cohort study. AB - BACKGROUND: The recent increase in the incidence of primary liver cancer in Canada has been attributed to a higher proportion of immigrants from countries endemic for hepatitis B virus (HBV) and hepatitis C virus (HCV). We examined hospital discharges for liver disease in Canada, focusing on those for all liver related diseases, HBV infection, HCV infection and primary liver cancer, by 3 immigration-related variables: immigration status, duration of residence in Canada and risk level of the source country. METHODS: We calculated annualized crude and age-standardized rates of a hospital stay in Canada for HBV infection, HCV infection, primary liver cancer and all liver-related diseases using data from the 2006 Canadian census (long form) linked to the Canadian Institute for Health Information Discharge Abstract Database for fiscal years 2006/07 to 2008/09. We estimated the odds of a hospital stay using logistic regression for the 3 immigration-related variables, adjusting for sociodemographic indicators. RESULTS: Immigrants were less likely than Canadian-born residents to be discharged with a diagnosis of any liver-related condition (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.78-0.89); however, they were more likely to be discharged with a diagnosis of HBV infection (OR 2.02, 95% CI 1.57-2.60) and primary liver cancer (OR 1.43, 95% CI 1.22-1.68). There was a clear association between a hospital stay for HBV infection and immigration from HBV-endemic countries (OR 5.15, 95% CI 3.87-6.84) and between a stay for HCV infection and immigration from HCV-endemic countries (OR 2.98, 95% CI 1.74-5.11). Adjustment for low income status and urban residence did not change the results. INTERPRETATION: Although the odds of a liver-related hospital stay were lower among immigrants than among those born in Canada, immigrants from countries at high risk for HBV infection, HCV infection and primary liver cancer were more likely than Canadian-born residents to have a corresponding liver-related hospital stay. These findings emphasize the importance of identifying immigrants with hepatitis and engaging them in care to prevent complications. PMID- 27398360 TI - Prevalence and predictors of facing a legal obligation to disclose HIV serostatus to sexual partners among people living with HIV who inject drugs in a Canadian setting:a cross-sectional analysis. AB - BACKGROUND: In October 2012, the Canadian Supreme Court ruled that people living with HIV must disclose their HIV status before sex that poses a "realistic possibility" of HIV transmission, clarifying that in circumstances where condom protected penile-vaginal intercourse occurred with a low viral load (< 1500 copies/mL), the realistic possibility of transmission would be negated. We estimated the proportion of people living with HIV who use injection drugs who would face a legal obligation to disclose under these circumstances. METHODS: : We used cross-sectional survey data from a cohort of people living with HIV who inject drugs. Participants interviewed since October 2012 who self-reported recent penile-vaginal intercourse were included. Participants self-reporting 100% condom use with a viral load consistently < 1500 copies/mL were assumed to have no legal obligation to disclose. Logistic regression identified factors associated with facing a legal obligation to disclose. RESULTS: We included 176 participants, 44% of whom were women: 94% had a low viral load, and 60% self reported 100% condom use. If condom use and low viral load were required to negate the realistic possibility of transmission, 44% would face a legal obligation to disclose. Factors associated with facing a legal obligation to disclose were female sex (adjusted odds ratio [OR] 2.19, 95% confidence interval [CI] 1.13-4.24), having 1 recent sexual partner (v. > 1) (adjusted OR 2.68, 95% CI 1.24-5.78) and self-reporting a stable relationship (adjusted OR 2.00, 95% CI 1.03-3.91). INTERPRETATION: Almost half the participants in our analytic sample would face a legal obligation to disclose to sexual partners under these circumstances (with an increased burden among women), adding further risk of criminalization within this marginalized and vulnerable community. PMID- 27398361 TI - Prevalence and management of dementia in primary care practices with electronic medical records: a report from the Canadian Primary Care Sentinel Surveillance Network. AB - BACKGROUND: The proportion of Canadians living with Alzheimer disease and related dementias is projected to rise, with an increased burden on the primary health care system in particular. Our objective was to describe the prevalence and management of dementia in a community-dwelling sample using electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), which consists of validated, national, point-of-care data from primary care practices. METHODS: We used CPCSSN data as of Dec. 31, 2012, for patients 65 years and older with at least 1 clinical encounter in the previous 2 years. A validated case definition for dementia was used to calculate the national and provincial prevalence rates, to examine variations in prevalence according to age, sex, body mass index, rural or urban residence, and select comorbid conditions, and to describe patterns in the pharmacologic management of dementia over time at the provincial level. RESULTS: The age-standardized prevalence of dementia among community-dwelling patients 65 years and older was 7.3%. Prevalence estimates increased with age; they also varied between provinces, and upward trends were observed. Dementia was found to be associated with comorbid diabetes, depression, epilepsy and parkinsonism. Most of the patients with dementia did not have a prescription for a dementia-related medication recorded in their EMR between 2008 and 2012 inclusive. Those who had a prescription were most often prescribed donepezil by their primary care provider. INTERPRETATION: Overall prevalence estimates for dementia based on EMR data in this sample managed in primary care were generally in line with previous estimates based on administrative data, survey results or clinical sources. PMID- 27398362 TI - Does the wait for lumbar degenerative spinal stenosis surgery have a detrimental effect on patient outcomes? A prospective observational study. AB - BACKGROUND: Waits for elective spine surgery are common in Canada. We examined whether a prolonged wait for surgery for lumbar degenerative spinal stenosis was detrimental to outcome. METHODS: In this prospective observational study, we enrolled 166 consecutive patients referred to our centre for treatment of lumbar degenerative spinal stenosis between 2006 and 2010. Outcome measures were assessed at referral, preoperatively and until 24 months postoperatively. Primary outcome measures were the physical and mental component summary scores of the 36 Item Short-Form Health Survey and the Oswestry Disability Index. Secondary outcome measures included the symptom severity scale of the Zurich Claudication Questionnaire, a numeric rating scale for back and leg pain, and patient satisfaction with treatment. Wait time was defined as the time from referral to surgery. RESULTS: The follow-up rate at 2 years was 85%. The median wait time was 349 days. All health-related quality of life measures deteriorated during the waiting period, but there was no significant correlation between wait time and magnitude of the change in outcome measure. At 6 months postoperatively, the Pearson correlation was significantly positive between wait time and change in disability (r = 0.223), Zurich Claudication Questionnaire score (r = 0.2) and leg pain score (r = 0.221). At 12 months, the correlation remained significant for change in disability (r = 0.205) and was significant for change in mental well being (r = -0.224). At 12 months, patients with a shorter wait (<= 12 months) showed greater improvement in mental well-being (mean difference in change [and 95% confidence interval (CI)] 5.7 [1.4-9.9]) and decrease in disability (-9.3 [95% CI -15.1 to -3.6]) and leg pain (-1.6 [95% CI -3.0 to -0.3]). There were no statistically significant differences in outcome or patient satisfaction with treatment between those with shorter and longer waits at 24 months. INTERPRETATION: Patients awaiting spinal surgery experienced deterioration in health-related quality of life irrespective of the length of wait time. However, longer waits were associated with a delay in recovery during the first year after surgery. PMID- 27398363 TI - Interventions for prevention of childhood obesity in primary care: a qualitative study. AB - BACKGROUND: Preventing childhood obesity is a public health priority, and primary care is an important setting for early intervention. Authors of a recent national guideline have identified a need for effective primary care interventions for obesity prevention and that parent perspectives on interventions are notably absent from the literature. Our objective was to determine the perspectives of primary care clinicians and parents of children 2-5 years of age on the implementation of an obesity prevention intervention within team-based primary care to inform intervention implementation. METHODS: We conducted focus groups with interprofessional primary care clinicians (n = 40) and interviews with parents (n = 26). Participants were asked about facilitators and barriers to, and recommendations for implementing a prevention program in primary care. Data were recorded and transcribed, and we used directed content analysis to identify major themes. RESULTS: Barriers existed to addressing obesity-related behaviours in this age group and included a gap in well-child primary care between ages 18 months and 4-5 years, lack of time and sensitivity of the topic. Trust and existing relationships with primary care clinicians were facilitators to program implementation. Offering separate programs for parents and children, and addressing both general parenting topics and obesity-related behaviours were identified as desirable. INTERPRETATION: Despite barriers to addressing obesity related behaviours within well-child primary care, both clinicians and parents expressed interest in interventions in primary care settings. Next steps should include pilot studies to identify feasible strategies for intervention implementation. PMID- 27398364 TI - Principles of fatigue in residency education: a qualitative study. AB - BACKGROUND: Proposals to implement fatigue-management strategies in residency education assume that medicine shares the view of other risk-adverse industries that fatigue is hazardous. This view is an essential underpinning of fatigue management strategies that other industries have embedded as part of their workplace occupational health and safety programs. We sought to explore how residents understand fatigue in the context of their training environment. METHODS: We interviewed 21 residents in 7 surgical and nonsurgical programs at Western University in 2014. All participants met the inclusion criteria of routinely working 24-hour call shifts while enrolled in their training program. Data collection and analysis occurred iteratively in keeping with constructivist grounded theory methodology and informed theoretical sampling to sufficiency. RESULTS: Four predominant principles of fatigue captured how the social learning environment shaped residents' perceptions of fatigue. These included the conceptualization of fatigue as (a) inescapable and therefore accepted, (b) manageable through experience, (c) necessary for future practice and (d) surmountable when required. INTERPRETATION: This study elaborates our understanding of how principles of fatigue are constructed and reinforced by the training environment. Whereas fatigue is seen as a collective hazard in other industries, our data showed that, in residency training, fatigue may be seen as a personal challenge. Consequently, fatigue-management strategies that conceptualize fatigue as an occupational threat may have a limited impact on resident behaviour and patient safety. PMID- 27398365 TI - Wait times to rheumatology care for patients with rheumatic diseases: a data linkage study of primary care electronic medical records and administrative data. AB - BACKGROUND: The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases. METHODS: We identified patients from primary care practices in the Electronic Medical Record Administrative data Linked Database who had referrals to Ontario rheumatologists over the period 2000-2013. To assess the full care pathway, we identified dates of symptom onset, presentation in primary care and referral from electronic medical records. Dates of rheumatologist consultations were obtained by linking with physician service claims. We determined the duration of each phase of the care pathway (symptom onset to primary care encounter, primary care encounter to referral, and referral to rheumatologist consultation) and compared them with established benchmarks. RESULTS: Among 2430 referrals from 168 family physicians, 2015 patients (82.9%) were seen by 146 rheumatologists within 1 year of referral. Of the 2430 referrals, 2417 (99.5%) occurred between 2005 and 2013. The main reasons for referral were osteoarthritis (32.4%) and systemic inflammatory rheumatic diseases (30.6%). Wait times varied by diagnosis and geographic region. Overall, the median wait time from referral to rheumatologist consultation was 74 (interquartile range 27-101) days; it was 66 (interquartile range 18-84) days for systemic inflammatory rheumatic diseases. Wait time benchmarks were not achieved, even for the most urgent types of referral. For systemic inflammatory rheumatic diseases, most of the delays occurred before referral. INTERPRETATION: Rheumatology wait times exceeded established benchmarks. Targeted efforts are needed to promote more timely access to both primary and rheumatology care. Routine linkage of electronic medical records with administrative data may help fill important gaps in knowledge about waits to primary and specialty care. PMID- 27398366 TI - Health services and policy research in the first decade at the Canadian Institutes of Health Research. AB - BACKGROUND: Health services and policy research is the innovation engine of a health care system. In 2000, the Canadian Institutes of Health Research (CIHR) was formed to foster the growth of all sciences that could improve health care. We evaluated trends in health services and policy research funding, in addition to determinants of funding success. METHODS: All applications submitted to CIHR strategic and open operating grant competitions between 2001 and 2011 were included in our analysis. Age, sex, size of research team, critical mass, season, year and research discipline were retrieved from application information. A cohort of 4725 applicants successfully funded between 2001 and 2005 were followed for 5 years to evaluate predictors of continuous funding. Multivariate generalized estimating equation logistic regression was used to estimate predictors of funding success and sustained funding. RESULTS: Between 2001 and 2011, 80 163 applications were submitted to open and strategic grant competitions. Over time, grant applications increased from 327 to 1137 per year, and annual funding increased from $12.6 to $48.0 million. Grant applications from young male researchers were more likely to be funded than those from female researchers (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.01-1.95), as were applications from larger research teams and institutions with a large critical mass. Only 24.0% of scientists whose first funded grant was in health services and policy research had sustained 5-year funding, compared with 52.8% of biomedical scientists (OR 0.34, 95% CI 0.24-0.49). INTERPRETATION: The CIHR has successfully increased the amount of health services and policy research in Canada. To enhance conditions for success, researchers should be encouraged to work in teams, request longer duration grants, resubmit unsuccessful applications and affiliate themselves with institutions with a greater critical mass. PMID- 27398367 TI - Medical end-of-life practices among Canadian physicians: a pilot study. AB - BACKGROUND: Medical end-of-life practices are hotly debated in Canada, and data from other countries are used to support arguments. The objective of this pilot study was twofold: to adapt and validate a questionnaire designed to measure the prevalence of these practices in Canada and the underlying decision-making process, and to assess the feasibility of a nationally representative study. METHODS: In phase 1, questionnaires from previous studies were adapted to the Canadian context through consultations with a multidisciplinary committee and based on a scoping review. The modified questionnaire was validated through cognitive interviews with 14 physicians from medical specialties associated with a higher probability of being involved with dying patients recruited by means of snowball sampling. In phase 2, we selected a stratified random sample of 300 Canadian physicians in active practice from a national medical directory and used the modified tailored method design for mail and Web surveys. There were 4 criteria for success: modified questions are clearly understood; response patterns for sensitive questions are similar to those for other questions; respondents are comparable to the overall sampling frame; and mean questionnaire completion time is less than 20 minutes. RESULTS: Phase 1: main modifications to the questionnaire were related to documentation of all other medical practices (including practices intended to prolong life) and a question on the proportionality of drugs used. The final questionnaire contained 45 questions in a booklet style. Phase 2: of the 280 physicians with valid addresses, 87 (31.1%) returned the questionnaire; 11 of the 87 declined to participate, for a response rate of 27.1% (n = 76). Most respondents (64 [84%]) completed the mail questionnaire. All the criteria for success were met. INTERPRETATION: It is feasible to study medical end-of-life practices, even for practices that are currently illegal, including the intentional use of lethal drugs. Results from this pilot study support conducting a large national study, but additional strategies would be necessary to improve the response rate. PMID- 27398368 TI - Hypertension screening and follow-up in children and adolescents in a Canadian primary care population sample: a retrospective cohort studystudy. AB - BACKGROUND: Uncertainty exists about the need to screen for hypertension in children and adolescents. Information on current screening and follow-up rates in Canadian community practices is not available. There are no Canadian guidelines on the subject. We sought to identify current rates of pediatric hypertension screening and follow-up in Canada. In addition, we examined patient and provider characteristics associated with rates of blood pressure screening. METHODS: We used electronic medical record data extracted on Apr. 1, 2013, from 79 family practices in Toronto. We identified children seen at least twice between the ages of 3 and 18 years, with at least 6 months between first and last encounter. We used Multivariate Poisson regression analysis to analyze variation in blood pressure measurement rates and associations with patient and physician factors. RESULTS: We identified 5996 children (62% of 9667 in total) who had at least 1 blood pressure measurement recorded. Of these children, 14% had at least 1 abnormal blood pressure measurement, and of those children, only 5% had a follow up measurement recorded within 6 months. After adjustment, increases in rates of blood pressure measurements were associated with greater number of encounters (rate ratio [RR] = 1.03, 95% confidence interval [CI] 1.02-1.04, p < 0.001), older age at first encounter (RR = 1.06, 95% CI 1.03-1.10, p = 0.002), and female sex (RR = 1.12, 95% CI 1.03-1.20, p = 0.006). Obesity or a recorded family history of hypertension were not associated with more blood pressure measurements. Female physicians recorded more blood pressure measurements than did male physicians (RR = 1.41, 95% CI 1.04-1.89, p = 0.02). INTERPRETATION: This screening measure was frequently done and appeared to be incompletely followed up. Clear guidance is needed; guideline developers should consider reviewing this topic. PMID- 27398369 TI - Effect of unintentional cyclophosphamide underdosing on diffuse large B-cell lymphoma response to chemotherapy: a retrospective review. AB - BACKGROUND: Between March 2012 and March 2013, a miscommunication in labelling between the drug compounder supplier and cancer centre pharmacies resulted in accidental overdilution of cyclophosphamide and gemcitabine used by several cancer centres in Canada. At our centre, 177 hematology patients were affected, among whom the largest subset of patients was those with diffuse large B-cell lymphoma. In this study, we evaluated the effect of such underdosing on disease response. METHODS: We conducted a retrospective cohort study involving all patients with diffuse large B-cell lymphoma who received at least 1 chemotherapy cycle containing diluted cyclophosphamide at our centre and compared them with a historical group of patients matched by stage and age. The primary outcome was event-free survival (a composite of disease progression or death). Secondary outcomes included complete remission and overall response rate. Groups were compared using unpaired Student t, chi2 or Fisher exact tests, as appropriate. Survival analysis was done using the Kaplan-Meier method. RESULTS: Event-free survival was no different between groups (log-rank p = 0.99). At a median follow up of 548 days, progression or death occurred in 21 of 77 patients in the case group (27.3%) and in 24 of 74 patients in the control group (32.4%) (p = 0.5). At the end of treatment, complete remission was achieved in 41 patients in the case group (53.2%) and 43 patients in the control group (57.3%) (p = 0.6), whereas overall response rate was 71.4% in the case group and 66.7% in the control group (p = 0.5). INTERPRETATION: Compared with a historical control group, we found no differences in event-free survival or response rates among patients with diffuse large B-cell lymphoma who received 1 or more doses of accidentally diluted cyclophosphamide-containing chemotherapy. PMID- 27398370 TI - Emergency department use by people with HIV in Ontario: a population-based cohort study. AB - BACKGROUND: Emergency department use may reflect poor access to primary care. Our objective was to compare rates and causes of emergency department use between adults living with and without HIV. METHODS: We conducted a population-based study involving Ontario residents living with and without HIV between Apr. 1, 2011, and Mar. 31, 2012. We frequency matched adults with HIV to 4 HIV-negative people by age, sex and census division, and used random-effects negative binomial regression to compare rates of emergency department use. We classified visits as low urgency or high urgency, and also examined visits for ambulatory care sensitive conditions. Hospital admission following an emergency department visit was a secondary outcome. RESULTS: We identified 14 534 people with HIV and 58 136 HIV-negative individuals. Rates of emergency department use were higher among people with HIV (67.3 v. 31.2 visits per 100 person-years; adjusted rate ratio 1.58, 95% confidence interval [CI] 1.51-1.65). Similar results were observed for low-urgency visits. With the exception of hypertension, visit rates for ambulatory care sensitive conditions were higher among people with HIV. People with HIV were also more likely than HIV-negative individuals to be admitted to hospital following an emergency department visit (adjusted odds ratio 1.55, 95% CI 1.43-1.69). INTERPRETATION: Compared with HIV-negative individuals, people with HIV had high rates of emergency department use, including potentially avoidable visits. These findings strongly support the need for comprehensive care for people with HIV. PMID- 27398371 TI - Traumatic brain injury in a rural indigenous population in Canada: a community based approach to surveillance. AB - BACKGROUND: Indigenous populations are disproportionately affected by traumatic brain injury. These populations rely on large jurisdiction surveillance efforts to inform their prevention strategies, which may not address their needs. We examined the incidence and determinants of traumatic brain injury in an indigenous population in the Terres-Cries-de-la-Baie-James health region of the province of Quebec and compared them with the incidence and determinants in 2 neighbouring health regions and in the province overall. METHODS: We conducted a retrospective population-based cohort study of patients in Quebec admitted to hospital with incident traumatic brain injury, stratified by health region (Terres-Cries-de-la-Baie-James, Nunavik and Nord-du-Quebec), from 2000 to 2012. We used MED-ECHO administrative data for case-finding. A subgroup analysis of adults in the Terres-Cries-de-la-Baie-James health region was completed to assess determinants of the severity of traumatic brain injury and patient outcomes. RESULTS: A total of 172 hospital admissions for incident traumatic brain injury occurred in the Terres-Cries-de-la-Baie-James region during the study period. The incidence was 92.1 per 100 000 person-years, and the adjusted incidence rate ratio was 1.84 (95% confidence interval 1.56-2.17) compared with the entire province. The incidence was higher than in the neighbouring nonindigenous population (Nord-du-Quebec) but significantly lower than in the neighbouring indigenous population (Nunavik). Determinants of traumatic brain injury in the Terres-Cries-de-la-Baie-James region differed from those in the neighbouring populations and in the entire province. INTERPRETATION: We found that the incidence rates and determinants of traumatic brain injury requiring hospital admission varied greatly between the three regions studied. Community-based surveillance efforts should be encouraged to inform the development of relevant prevention strategies. PMID- 27398372 TI - Association between registered nurse staffing and management outcomes of patients with type 2 diabetes within primary care: a cross-sectional linkage study. AB - BACKGROUND: As the organization of primary care continues to evolve toward more interdisciplinary team structures, demonstrating effectiveness of care delivery is becoming important, particularly for nonphysician providers. Nurses are the most common nonphysician provider within primary care. The purpose of this study was to examine the relation between primary care delivery models that incorporate registered nurses and clinical outcomes of patients with type 2 diabetes. METHODS: Patient data from the Canadian Primary Care Sentinel Surveillance Network were matched with survey data from 15 Family Health Team practices in southeastern Ontario. Included patients were adults with type 2 diabetes mellitus who had at least 1 primary care encounter at a Family Health Team practice that completed the organizational survey between Apr. 1, 2013, and Mar. 31, 2014. The clinical outcomes explored included hemoglobin A1c, fasting plasma glucose, blood pressure, low-density lipoprotein cholesterol and urine albumin:creatinine ratio. RESULTS: Of the 15 practices, 13 (86.7%) had at least 1 registered nurse. The presence of 1 or more registered nurses in the practice was associated with increased odds of patients' having their hemoglobin A1c, fasting plasma glucose, blood pressure and low-density lipoprotein cholesterol values meet recommended targets. Practices with the lowest ratios of patients with diabetes to registered nurse had a significantly greater proportion of patients with hemoglobin A1c and fasting plasma glucose values on target than did practices with the highest ratios of patients to registered nurse (p < 0.01 and p = 0.03, respectively). INTERPRETATION: The findings suggest that registered nurse staffing within primary care practice teams contributes to better diabetic care, as measured by diabetes management indicators. This study sets the groundwork for further exploration of nursing and organizational contributions to patient care in the primary care setting. PMID- 27398373 TI - Processes of patient-centred care in Family Health Teams: a qualitative study. AB - BACKGROUND: Patient-centred care, access to care, and continuity of and coordination of care are core processes in primary health care delivery. Our objective was to evaluate how these processes are enacted by 1 primary care model, Family Health Teams, in Ontario. METHODS: Our study used grounded theory methodology to examine these 4 processes of care from the perspective of health care providers. Twenty Family Health Team practice sites in Ontario were selected to represent maximum variation (e.g., location, year of Family Health Team approval). Semi-structured interviews were conducted with each participant. A constant comparative approach was used to analyze the data. RESULTS: Our final sample population involved 110 participants from 20 Family Health Teams. Participants described how their Family Health Team strived to provide patient centred care, to ensure access, and to pursue continuity and coordination in their delivery of care. Patient-centred care was provided through a variety of means forging the links among the other processes of care. Participants from all teams articulated a commitment to timely access, spontaneously expressing the importance of access to mental health services. Continuity of care was linked to both access and patient-centred care. Coordination of care by the team was perceived to reduce unnecessary walk-in clinic and emergency department visits, and facilitated a smoother transition from hospital to home. INTERPRETATION: These 4 processes of patient care were inextricably linked. Patient-centred care was the focal point, and these processes in turn served to enhance the delivery of patient-centred care. PMID- 27398374 TI - Northern perspectives on medical elective tourism: a qualitative study. AB - BACKGROUND: The Royal College of Physicians and Surgeons of Canada recognizes education to be necessary for doctors to provide culturally safe care. Communities in northern Canada have large populations of Aboriginal people and other marginalized groups. Our goal was to identify the elements of appropriate predeparture curricula for these medical trainees. METHODS: We conducted our study in Kenora, Ontario. With the help of a core collaborative group and the support of the local Aboriginal Health Access Centre, we interviewed a purposive sample of community members about their interactions with trainees from southern Canada. Aboriginal and non-Aboriginal researchers with roots in northern and southern Canada brought perspectives to the inductive analysis. RESULTS: We conducted 17 semistructured interviews between February and March 2014. Participants felt that southern trainees were inadequately educated in northern politics, society and history. They identified 2 more themes: determinants of health affecting the local Aboriginal population, and provider and patient factors affecting delivery of culturally competent care. Participants also shared ideas on how best to implement this content into curricula. INTERPRETATION: Providing culturally competent care to northern communities is a complex process requiring education. Using a collaborative method, we were able to delineate the experiences of members of a northern community and identify knowledge gaps of southern trainees travelling there. Our results provide a foundation for the content and structure of formal predeparture curricula to enable such trainees to provide culturally safe care. PMID- 27398375 TI - Attitude to health risk in the Canadian population: a cross-sectional survey. AB - BACKGROUND: Risk is a ubiquitous part of health care. Understanding how people respond to risks is important for predicting how populations make health decisions. Our objective was to seek preliminary descriptive insights into the attitude to health risk in the Canadian population and factors associated with heterogeneity in risk attitude. METHODS: We used a large market-research panel to survey (in English and French) a representative sample of the Canadian general population that reflected the age, sex and geography of the population. The survey included the Health-Risk Attitude Scale, which predicts how a person resolves risky health decisions related to treatment, prevention of disease and health-related behaviour. In addition, we assessed participants' numeracy and risk understanding, as well as income band and level of education. We summarized the responses, and we explored the independent associations between demographics, numeracy, risk understanding and risk attitude in multivariable models. RESULTS: Of 6780 respondents, 4949 (73.0%) were averse to health risks; however, but there was considerable heterogeneity in the magnitude of risk aversion. We found significant gradients of risk averse attitudes with increasing age and being female (p < 0.001) using the multivariable model. French-speaking participants appeared to be more risk averse than those who were English-speaking (p < 0.001), as were individuals scoring higher on the Subjective Numeracy Scale (p < 0.001). INTERPREATION: In general, Canadians were averse to health risks, but we found that a sizeable, identifiable group of risk takers exists. Heterogeneity in preferences for risk can explain variations in health care utilization in the context of patient-centred care. Understanding risk preference heterogeneity can help guide policy and assist in patient-physician decisions. PMID- 27398376 TI - Trends in the use and cost of antipsychotics among older adults from 2007 to 2013: a repeated cross-sectional study. AB - BACKGROUND: Recently, several new atypical antipsychotic agents have been introduced in Ontario, and regulatory warnings have been issued regarding use of atypical antipsychotics in older adults. We sought to establish the impact of newer atypical antipsychotics on prescribing rates and costs. METHODS: We performed a population-based cross-sectional study of Ontario adults aged 65 years or more using atypical antipsychotics from Jan. 1, 2007, to Mar. 31, 2013. These people have universal access to publicly funded drugs through the Ontario Health Insurance Plan and the Ontario Drug Benefit. We conducted time-series analysis to assess the impact of the introduction of new atypical antipsychotics on rates of use of atypical antipsychotics and associated expenditures. RESULTS: Rates of atypical antipsychotic use increased following the introduction of new agents in 2009, from 27.6 users per 1000 older adults in the third quarter of 2009 to 29.1 users per 1000 older adults at the end of the study period (p = 0.04). Although prescribing rates for the newer atypical agents (paliperidone, ziprasidone and aripiprazole) remained low relative to their older counterparts (risperidone, olanzapine and quetiapine), rates of aripiprazole use rose to 1.0 user per 1000 older adults by the end of the study period. The proportion of prescriptions that were for brand-name agents fell from 57.5% in the second quarter of 2007 to 6.1% in the second quarter of 2009, and then rose to 11.7% by the end of the study period. By the first quarter of 2013, newer atypical antipsychotic agents were used by 4.4% of atypical antipsychotic users but accounted for 14.1% ($1.2 million of $8.5 million) of atypical antipsychotic expenditures. INTERPRETATION: Although the overall prevalence of use of new atypical antipsychotic agents remains low, their introduction has led to increased prescribing of this class of drugs in older adults. Given the potential cost implications, further study of these trends would be prudent. PMID- 27398377 TI - Smoke-free homes, smoking susceptibility and familial smoking among never-smoking high school students: a cross-sectional analysis. AB - BACKGROUND: Research has shown that living in a smoke-free home has a positive effect on adolescents' perceived acceptance of smoking. However, the relationship between smoke-free homes and adolescent smoking behaviours remains unclear. The aim of this study was to examine the association between smoke-free homes and smoking susceptibility among high school students, and to determine whether these associations persist when analyses are stratified by familial smoking status. METHODS: We conducted a random cross-sectional survey (2012/2013 Youth Smoking Survey) of primary, junior and high school students in Canada (n = 47 203). Multivariable logistic regression analyses were used to examine the associations between smoke-free homes and susceptibility to smoking among never-smoking high school students, with and without stratification by familial smoking. RESULTS: Analyses showed that adolescents living in a smoke-free home had reduced odds of being susceptible to smoking (odds ratio [OR] 0.582, 95% confidence interval [CI] 0.428-0.791) compared with their peers living in households where smoking was permitted. When adolescents had other family members who were smokers, having a smoke-free home was not significantly associated with reduced smoking susceptibility (OR 0.878, 95% CI 0.721-1.071). INTERPRETATION: Our results suggest that smoke-free homes may influence future smoking initiation. Optimal success in preventing youth smoking uptake necessitates having a coherent antismoking message between the home smoking environment and familial smoking behaviour. PMID- 27398378 TI - Development of a conceptual framework for understanding financial barriers to care among patients with cardiovascular-related chronic disease: a protocol for a qualitative (grounded theory) study. AB - BACKGROUND: Patients with cardiovascular-related chronic diseases may face financial barriers to accessing health care, even in Canada, where universal health care insurance is in place. No current theory or framework is adequate for understanding the impact of financial barriers to care on these patients or how they experience financial barriers. The overall objective of this study is to develop a framework for understanding the role of financial barriers to care in the lives of patients with cardiovascular-related chronic diseases and the impact of such barriers on their health. METHODS: We will perform an inductive qualitative grounded theory study to develop a framework to understand the effect of financial barriers to care on patients with cardiovascular-related chronic diseases. We will use semistructured interviews (face-to-face and telephone) with a purposive sample of adult patients from Alberta with at least 1 of hypertension, diabetes, heart disease or stroke. We will analyze interview transcripts in triplicate using grounded theory coding techniques, including open, focused and axial coding, following the principle of constant comparison. Interviews and analysis will be done iteratively to theoretical saturation. Member checking will be used to enhance rigour. INTERPRETATION: A comprehensive framework for understanding financial barriers to accessing health care is instrumental for both researchers and clinicians who care for patients with chronic diseases. Such a framework would enable a better understanding of patient behaviour and nonadherence to recommended medical therapies and lifestyle modifications. PMID- 27398379 TI - Temporal trends in vascular trauma in Ontario, 1991-2009: a population-based study. AB - BACKGROUND: Vascular injuries add substantial complexity to trauma care, yet Canadian epidemiologic data on such injuries are not readily available. We conducted a retrospective cross-sectional study to examine temporal trends in the rate of hospital admissions for vascular injuries from 1991 to 2009 in Ontario. METHODS: Individuals of any age admitted to hospital because of vascular trauma in Ontario were included. Details of vascular injury and patient demographic characteristics were recorded, hospital admission rates estimated and analyses stratified by sex, age, mechanism of injury, economic status and geographic location. Time-series analysis was used to examine trends in hospital admission rates. RESULTS: Of the 8252 hospital admissions for vascular trauma, 4287 (52.0%) involved injuries to the upper limb and 1819 (22.0%) were due to transport related causes. Overall, the annual rate declined significantly over time, from 3.3 per 100 000 in 1991 to 2.7 per 100 000 in 2009 (p < 0.01). The subgroups with the highest rates were young men, patients with a low economic status and those living in a rural location. Declines occurred in both sexes and in all age groups except those 65 years and older. The rates of vascular injury to the neck, thorax, upper limbs and lower limbs declined over time, but not the rate of abdominal vascular injury. Although the rate of non-transport-related vascular injuries declined, the rate of transport-related vascular injuries did not change significantly over time. Decreases in annual rates occurred in both low- and high economic status groups and in urban populations but not in rural populations. INTERPRETATION: Overall, the annual rate of hospital admissions for vascular trauma declined significantly in Ontario over the study period. Our findings have important implications for public health and the development of injury-prevention strategies, particularly for population subgroups at high risk of vascular injury. PMID- 27398381 TI - Patterns of skin disease in a sample of the federal prison population: a retrospective chart review. AB - BACKGROUND: Dermatology in vulnerable populations is under-researched. Our objective was to analyze the most commonly referred skin diseases affecting the Correctional Service Canada inmates in Ontario. METHODS: An observational, cross sectional, retrospective chart review of inmate patients seen from 2008 until 2013 was performed. Two groups of patients were included in the analysis: those assessed in-person, and those evaluated by e-consult. RESULTS: In the in-person patient group, the 3 most common diagnoses were acne, psoriasis and other superficial mycoses. For the e-consult group, the 3 most frequent diagnoses were acne, psoriasis and rosacea. There was a clear bias toward more inmates being seen in-person where the service was provided (Collins Bay Institution) than from other correctional institutions in Eastern Ontario. INTERPRETATION: Most of the skin diseases that affected the incarcerated population studied were common afflictions, similar to those affecting the general population, which is in agreement with other studies. Future studies investigating skin diseases in male and female inmates across Canada would bestow more generalizable data. PMID- 27398380 TI - Mechanical thrombectomy in patients with acute ischemic stroke: a cost-utility analysis. AB - BACKGROUND: The beneficial effects of endovascular treatment with new-generation mechanical thrombectomy devices compared with intravenous thrombolysis alone to treat acute large-artery ischemic stroke have been shown in randomized controlled trials (RCTs). This study aimed to estimate the cost utility of mechanical thrombectomy compared with the established standard of care. METHODS: We developed a Markov decision process analytic model to assess the cost effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis versus treatment with intravenous thrombolysis alone from the public payer perspective in Canada. We conducted comprehensive literature searches to populate model inputs. We estimated the efficacy of mechanical thrombectomy plus intravenous thrombolysis from a meta-analysis of 5 RCTs, and we used data from the Oxford Vascular Study to model long-term clinical outcomes. We calculated incremental cost-effectiveness ratios (ICER) using a 5-year time horizon. RESULTS: The base case analysis showed the cost and effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis to be $126 939 and 1.484 quality-adjusted life-years (QALYs), respectively, and the cost and effectiveness of treatment with intravenous thrombolysis alone to be $124 419 and 1.273 QALYs, respectively. The mechanical thrombectomy plus intravenous thrombolysis strategy was associated with an ICER of $11 990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of treatment with mechanical thrombectomy plus intravenous thrombolysis being cost-effective was 57.5%, 89.7% and 99.6% at thresholds of $20 000, $50 000 and $100 000 per QALY gained, respectively. The main factors influencing the ICER were time horizon, extra cost of mechanical thrombectomy treatment and age of the patient. INTERPRETATION: Mechanical thrombectomy as an adjunct therapy to intravenous thrombolysis is cost-effective compared with treatment with intravenous thrombolysis alone for patients with acute large-artery ischemic stroke. PMID- 27398382 TI - Predictors of diagnostic neuroimaging delays among adults presenting with symptoms suggestive of acute stroke in Ontario: a prospective cohort study. AB - BACKGROUND: Many studies have examined the timeliness of thrombolysis for acute ischemic stroke, but less is known about door-to-imaging time. We conducted a prospective cohort study to assess the timing of neuroimaging among patients with suspected acute stroke in the province of Ontario, Canada, and to examine factors associated with delays in neuroimaging. METHODS: We included all patients 18 years and older with suspected acute stroke seen at hospitals with neuroimaging capacity within the Ontario Stroke Registry between Apr. 1, 2010, and Mar. 31, 2011. We used a hierarchical, multivariable Cox proportional hazards model to evaluate the association between patient and hospital factors and the likelihood of receiving timely neuroimaging (<= 25 min) after arrival in the emergency department. RESULTS: A total of 13 250 patients presented to an emergency department with stroke-like symptoms during the study period. Of the 3984 who arrived within 4 hours after symptom onset, 1087 (27.3%) had timely neuroimaging. The factors independently associated with an increased likelihood of timely neuroimaging were less time from symptom onset to presentation, more severe stroke, male sex, no history of stroke or transient ischemic attack, arrival to hospital from a setting other than home and presentation to a designated stroke centre or an urban hospital. INTERPRETATION: A minority of patients with stroke like symptoms who presented within the 4-hour thrombolytic treatment window received timely neuroimaging. Neuroimaging delays were influenced by various patient and hospital factors, some of which are modifiable. PMID- 27398383 TI - Frequency and cost of potentially inappropriate prescribing for older adults: a cross-sectional study. AB - BACKGROUND: Many medications pose greater health risks when prescribed for older adults, compared with available pharmacologic and nonpharmacologic alternatives. We sought to quantify the frequency and cost of potentially inappropriate prescribing for older women and men in Canada. METHODS: Using data for 2013 from the National Prescription Drug Utilization Information System database, which contains prescription claims from publicly financed drug plans in all provinces except for Quebec, we identified the frequency of prescribing and cost of potentially inappropriate medications dispensed to provincial drug plan enrollees aged 65 years or more. Potentially inappropriate prescriptions were defined with the use of the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. RESULTS: For the 6 provinces with relatively complete data coverage (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario and Prince Edward Island), 37% of older people filled 1 or more prescription meeting the Beers Criteria. A higher proportion of women (42%) than men (31%) filled potentially inappropriate prescriptions. The highest rates of prescribing of potentially inappropriate medications were among women aged 85 or more (47%). Benzodiazepines and other hypnotics were the leading contributors to the overall frequency of and sex differences in prescribing of potentially inappropriate drugs among older adults. We estimated that $75 per older Canadian, or $419 million in total, was spent on potentially inappropriate medications outside of hospital settings in 2013. INTERPRETATION: Prescribing of potentially inappropriate medications for older adults is common and costly in Canada, especially for women. Multipronged and well-coordinated strategies to reduce the use and cost of potentially inappropriate drugs would likely generate significant health system savings while simultaneously generating major benefits to patient health. PMID- 27398385 TI - Metabolic Bone Disease in Viral Cirrhosis: A Prospective Study. AB - Background/Aim. Metabolic Bone disorders are well-recognized extrahepatic complications of cirrhosis. The aim was to report their prevalence and the associated factors to their development in patients with viral cirrhosis. Patients and Methods. All consecutive patients with viral cirrhosis were prospectively enrolled. Parathyroid hormone, 25-hydroxyvitamin D, liver function, and phosphocalcic tests were measured in all patients. Bone mineral density was measured at the lumbar spine and total hip by dual-energy X-ray absorptiometry. Data were analyzed using SPSS software. Results. Forty-six cirrhotic patients were included with hepatitis C (87%) and hepatitis B (13%). The Child-Pugh score was grade A in 87% of cases and grade B in 13%. Thirty-seven patients had decreased bone mineral density with osteopenia in 24 patients and osteoporosis in 13 patients. Decreased 25-hydroxyvitamin D was found in 95.6% of cases. Bone disorders were significantly more frequent in old patients with low body mass index, long duration of liver disease, and low 25-hydroxyvitamin D level. None of these factors was an independent factor associated with bone disorders. Conclusion. Our study revealed a high prevalence of metabolic bone disorders among viral cirrhotic patients. Consequently, bone mineral density assessment should be performed systematically in all cirrhotic patients. PMID- 27398384 TI - Effects of Antioxidant N-acetylcysteine Against Paraquat-Induced Oxidative Stress in Vital Tissues of Mice. AB - Paraquat (PQ) is a commonly used herbicide that induces oxidative stress via reactive oxygen species (ROS) generation. This study aimed to investigate the effects of the antioxidant N-acetylcysteine (NAC) against PQ-induced oxidative stress in mice. Male Balb/C mice (24) were randomly divided into 4 groups and treated for 3 weeks: 1) control (saline), 2) NAC (0.5% in diet), 3) PQ (20 mg/kg, IP) and 4) combination (PQ + NAC). Afterwards mice were sacrificed and oxidative stress markers were analyzed. Our data showed no significant change in serum antioxidant capacity. PQ enhanced lipid peroxidation (MDA) levels in liver tissue compared to control whereas NAC decreased MDA levels (p<0.05). NAC significantly increased MDA in brain tissue (p<0.05). PQ significantly depleted glutathione (GSH) levels in liver (p=0.001) and brain tissue (p<0.05) but non-significant GSH depletion in lung tissue. NAC counteracted PQ, showing a moderate increase GSH levels in liver and brain tissues. PQ significantly increased 8-oxodeoxyguanosine (8-OH-dG) levels (p<0.05) in liver tissue compared to control without a significant change in brain tissue. NAC treatment ameliorated PQ-induced oxidative DNA damage in the liver tissue. PQ significantly decreased the relative mtDNA amplification and increased the frequency of lesions in liver and brain tissue (p<0.0001), while NAC restored the DNA polymerase activity in liver tissue but not in brain tissue. In conclusion, PQ induced lipid peroxidation, oxidative nuclear DNA and mtDNA damage in liver tissues and depleted liver and brain GSH levels. NAC supplementation ameliorated the PQ-induced oxidative stress response in liver tissue of mice. PMID- 27398386 TI - Impact of Eighteen-Year Varied Compliance to Onchocerciasis Treatment with Ivermectin in Sentinel Savannah Agrarian Communities in Kaduna State of Nigeria. AB - Baseline and impact assessment data were generated in 1994 (n = 532) and 2011 (n = 593) from 6 sentinel villages with generalized onchocerciasis. Only volunteers and a cohort (n = 445, 75%) were screened at both visits. Each village had received 11 (64.7%) annual treatments and 92.6%, range 88.7-100%, treatment compliance. Overall mean number of treatment was 2.9 +/- 1.6 with a range 2.0 +/- 1.2-3.3 +/- 0.6. Significant decreases in skin microfilaria prevalence from 201 (38%) to 0 (0%), palpable nodule from 77 (15%) to 4 (0.7%), dermal changes from 51 (9.6%) to 2 (0.04%), optic nerve disease from 24 (4.5%) to 4 (2.0%), and onchocercal inducible ocular lesions from 31 (5.8%) to 12 (2.0%) were recorded, P < 0.05, (t-test of unpaired data). Cases of glaucoma, 8 (1.4%), and blindness, 6 (1.05%), remained unchanged. Visual acuity >=6/24 in one or both eyes, 198 (33.45%); cataract, 169 (28.5%); pterygium 157 (26.5%); and acute senilis, 165 (27.9%), were significantly increased and positively correlated with increase in age (R (2) = 0.898 - 0.949). Dissected parous Simulium damnosum caught (n = 222) were without infective third stage larva. Active onchocerciasis transmission seems halted despite varied compliance to long-term ivermectin treatment. We recommend continued surveillance and targeted treatment of controlled and hypoendemic areas. PMID- 27398387 TI - Efficacy and Safety of Paromomycin in Treatment of Post-Kala-Azar Dermal Leishmaniasis. AB - Background. Post-kala-azar dermal leishmaniasis (PKDL) plays an important role in maintaining endemicity of visceral leishmaniasis and its transmission. Treatment regimens for PKDL are toxic and require 3-4 months of hospitalization. These long and arduous regimens result in extensive noncompliance. There is an urgent need to develop a safe, effective, and acceptable regimen for the treatment of PKDL. Paromomycin (PM) has been recently approved in India for treatment of visceral leishmaniasis (VL); hence we tested its efficacy in patients with PKDL. Methods. In this exploratory study, 31 patients with PKDL aged 10 years and above were administered PM 11 mg/kg daily intramuscularly for 45 days and followed up for one year. Results. Out of 31 patients, 7 patients were lost to followup at 1 year and 9 (37.5%) got cured with complete disappearance of lesion, while 15 (62.5%) showed no improvement by per protocol analysis. Conclusion. Cure rate with 45 intramuscular injections of PM was unacceptably low though there was no serious side effect of the drug. Whether paromomycin can be used in multidrug therapy to shorten the duration of treatment should be the next logical step for investigation. PMID- 27398388 TI - Alcohol, Substance Use and Psychosocial Competence of Adolescents in Selected Secondary Schools in Uganda: A Cross Sectional Survey. AB - AIMS: 1) To determine the nature and extent of alcohol and substance use and 2) To describe the relationship between alcohol use and psychosocial competence among secondary school youths in Northern and Central Uganda. STUDY DESIGN: This was a cross-sectional study. PLACE AND DURATION OF STUDY: Departments of Mental Health, Gulu University (Northern Uganda) and Department of Psychiatry, Makerere University College of Health Sciences (Central Uganda) between September 2011 and April 2012. METHODOLOGY: Four (4) and eight (8) secondary schools located in the rural and urban areas of Gulu and Kampala districts respectively were randomly selected to participate in the survey. A total of 3,200 students aged 12 to 24 years were recruited by proportionate multistage sampling. Data was collected using a socio-demographic questionnaire that included questions about nature and frequency of alcohol and substance use. A pre-tested self-administered survey questionnaire with scales to measure components of psychosocial competence (PSC) was administered. Data was entered in Epidata, and exported to SPSS version 16.0 for analysis. Psychosocial competence was classified as high or low depending on the responses in the sub-scales of decision making, self efficacy, empathy, emotional awareness, coping with stress and emotions, and accurate self assessment and self-confidence. RESULTS: A total of 2,902 questionnaires comprising of 2,502, (86.2%) from Kampala district and 400 (13.8%)) from Gulu district were analyzed. Male to female ratio was 1:1 with an age range of 12 to 24 years and a mean of 16.5. About 70.1% had ever used alcohol and substances. Only 39.1% used substances regularly. The commonest substance used was alcohol (23.3%), followed by kuber (10.8%), khat (10.5%), aviation fuel (10.1%), cannabis (9.2%) and cigarettes (5.9%). Respondents from the Gulu district were twice more likely to use all substances. Users and regular users from the North Northern Uganda had lower psychosocial competence. Factors significantly associated with non-use of alcohol were high levels of self-confidence, non-use of cannabis and kuber and age. In the alcohol user groups, a high level of coping was associated with discontinued and experimental use of drugs of abuse. CONCLUSION: More than two-thirds (70.1%) of young people in this study had ever used substances of abuse only once and slightly over a third had used it regularly. From the perspectives of service provision, mental health promotion and prevention of illicit substance use, school mental health programmes that target both non-users and users are recommended. PMID- 27398389 TI - Bayes and the Law. AB - Although the last forty years has seen considerable growth in the use of statistics in legal proceedings, it is primarily classical statistical methods rather than Bayesian methods that have been used. Yet the Bayesian approach avoids many of the problems of classical statistics and is also well suited to a broader range of problems. This paper reviews the potential and actual use of Bayes in the law and explains the main reasons for its lack of impact on legal practice. These include misconceptions by the legal community about Bayes' theorem, over-reliance on the use of the likelihood ratio and the lack of adoption of modern computational methods. We argue that Bayesian Networks (BNs), which automatically produce the necessary Bayesian calculations, provide an opportunity to address most concerns about using Bayes in the law. PMID- 27398390 TI - Impact of Income on Small Area Low Birth Weight Incidence Using Multiscale Models. AB - Low birth weight (LBW) is an important public health issue in the US as well as worldwide. The two main causes of LBW are premature birth and fetal growth restriction. Socio-economic status, as measured by family income has been correlated with LBW incidence at both the individual and population levels. In this paper, we investigate the impact of household income on LBW incidence at different geographical levels. To show this, we choose to examine LBW incidences collected from the state of Georgia, in the US, at both the county and public health (PH) district. The data at the PH district are an aggregation of the data at the county level nested within the PH district. A spatial scaling effect is induced during data aggregation from the county to the PH level. To address the scaling effect issue, we applied a shared multiscale model that jointly models the data at two levels via a shared correlated random effect. To assess the benefit of using the shared multiscale model, we compare it with an independent multiscale model which ignores the scale effect. Applying the shared multiscale model for the Georgia LBW incidence, we have found that income has a negative impact at both the county and PH levels. On the other hand, the independent multiscale model shows that income has a negative impact only at the county level. Hence, if the scale effect is not properly accommodated in the model, a different interpretation of the findings could result. PMID- 27398391 TI - Visit Patterns for Severe Mental Illness with Implementation of Integrated Care: A Pilot Retrospective Cohort Study. AB - There is increasing interest in models that integrate behavioral health services into primary care. For patients with severe mental illness, a population with disproportionate morbidity and mortality, little is known about the impact of such models on primary care clinic utilization and provider panels. We performed a retrospective cohort pilot study examining visit patterns for 1,105 patients with severe mental illness (SMI), overall and by provider, before and after the implementation of a primary care behavioral health model which had a ramp up period from 5/06-8/07. We used 2003-2012 electronic health record data from two clinics of a Federally Qualified Health Center and conducted interrupted time series and chi-square analyses. During the intervention period there was a significant increase in the proportion of visits per month to the clinic for patient with SMI relative to overall visits (0.27; 95% CI 0.22-0.32). After the intervention period, this rate declined (-0.23; -0.19-0.28) but remained above the pre-intervention period. After integration of behavioral health into our primary care clinics, there was a sharp increase in the number of patients with severe mental illness, suggesting patient willingness to explore receiving care under this model. Clinics looking to adopt the model should be mindful of potential changes in patient subpopulations and proactively manage this transition. PMID- 27398392 TI - Role of the sigmaRs for Development of Medications. PMID- 27398393 TI - Preclinical Efficacy of Novel Vesicular Monoamine Transporter 2 Inhibitors as Antagonists of d-Methamphetamine Self-Administration in Rats. PMID- 27398394 TI - Cocaine Antagonists; Studies on Cocaine Self-Administration. PMID- 27398395 TI - Self-Administration of JWH-018 A Synthetic Cannabinoid in Experimentally Naive Rats. PMID- 27398396 TI - Functions of the human frontoparietal attention network: Evidence from neuroimaging. AB - Human frontoparietal cortex has long been implicated as a source of attentional control. However, the mechanistic underpinnings of these control functions have remained elusive due to limitations of neuroimaging techniques that rely on anatomical landmarks to localize patterns of activation. The recent advent of topographic mapping via functional magnetic resonance imaging (fMRI) has allowed the reliable parcellation of the network into 18 independent subregions in individual subjects, thereby offering unprecedented opportunities to address a wide range of empirical questions as to how mechanisms of control operate. Here, we review the human neuroimaging literature that has begun to explore space based, feature-based, object-based and category-based attentional control within the context of topographically defined frontoparietal cortex. PMID- 27398397 TI - Bladder Cancer Patient Advocacy: A Global Perspective. AB - Over the past 20 years, cancer patient advocacy groups have demonstrated that patient engagement in cancer care is essential to improving patient quality of life and outcomes. Bladder cancer patient advocacy only began 10 years ago in the United States, but is now expanding around the globe with non-profit organizations established in Canada, the United Kingdom and Italy, and efforts underway in Australia. These organizations, at different levels of maturity, are raising awareness of bladder cancer and providing essential information and resources to bladder cancer patients and their families. The patient advocacy organizations are also helping to advance research efforts by funding research proposals and facilitating research collaborations. Strong partnerships between these patient advocates and the bladder cancer medical community are essential to ensuringsustainability for these advocacy organizations, increasing funding to support advances in bladder cancer treatment, and improving patient outcomes. PMID- 27398398 TI - Alvimopan in an Enhanced Recovery Program Following Radical Cystectomy. AB - Background: Radical cystectomy (RC) carries a high complication rate, including post-operative ileus. Alvimopan is an FDA approved peripherally acting MU-opioid receptor antagonist that has shown favorable results for improved recovery of gastro-intestinal function resulting in decreased hospital length of stay. Many enhanced recovery pathways (ERP) have been published demonstrating improved outcomes with decreased hospital stay and morbidity. Objective: We evaluated the addition of alvimopan to an ERP in patients undergoing RC. Methods: Patients undergoing RC at our institution during the implementation phase of alvimopan to our established ERP were retrospectively reviewed. Effect of alvimopan as it related to the use of nasogastric tubes, time to initiation of regular diet, and length of hospital stay was assessed using Chi-squared and Student's T-tests. Linear regression was performed for univariate analysis and binary logistic regression was performed as a multivariate assessment of the effect of alvimopan. Results: Between July 2011 and January 2013, 80 patients were identified who underwent RC under the ERP (34 alvimopan and 46 standard care). Age, sex, neoadjuvant chemotherapy, surgical technique (open vs. robotic), and type of urinary diversion were not different between groups. Alvimopan was associated with a reduction in mean time to regular diet (5.3 vs 4.1 days, p < 0.01) and a reduction in mean length of hospital stay (6.9 vs 5.7 days, p = 0.01). After controlling for other variables, alvimopan usage predicted for shorter time to regular diet and total hospital stay. Conclusions: Alvimopan may help to improve time to regular diet and decrease hospital stay in patients on an enhanced recovery pathway. PMID- 27398399 TI - Correlates and Predictors of Increasing Waist Circumference in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study. AB - Type 2 diabetes mellitus (type 2 DM) has become a disease of public health concern worldwide. Obesity and elevated blood pressure have been shown to be comorbidities of type 2 DM. In this cross-sectional study in Tamale, Ghana, we determined the prevalence of abdominal obesity among type 2 DM patients. Furthermore, we examined the demographic, clinical, and anthropometric predictors of increasing waist circumference in this population. Three hundred type 2 DM patients attending the outpatient diabetes clinic of the Tamale Teaching Hospital, Ghana, were recruited for the study. Waist circumference (WC) and hip circumferences were measured appropriately. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) and fasting plasma glucose (FPG) were taken from the personal health record files of patients. Demographic data were obtained. Pearson correlation and multiple linear regression models were employed to identify predictors of increasing WC. The prevalence of abdominal obesity was 77.0% and was significantly higher in women than in men. A positive correlation was observed between waist-to-hip ratio (WHR) and WC (r = 0.56, P < 0.001), female gender (r = 0.73, P < 0.001), and age (r = 0.20, P < 0.001). A high prevalence of abdominal obesity was observed. Predictors of increasing WC were gender, age, FPG, and WHR. PMID- 27398400 TI - Covariations between Shell-Growth Parameters and the Control of the Ranges of Variation of Functionally Relevant Shell-Shape Parameters in Bivalves: A Theoretical Approach. AB - Major traits of shell shape in bivalves may alternatively be described in terms of (i) functionally relevant parameters, assumed to play a significant role in the adaptation of bivalves molluscs to their environments (such as the shell outline elongation E, ventral convexity K, and dissymmetry D), or (ii) growth based parameters, directly controlled by the animal. Due to the geometrical linkage between functionally-relevant and growth-based parameters, adaptive constraints that may either widen or narrow the respective ranges of variations of the functional parameters lead to the onset of specific covariations (either positive or negative) between the growth-based parameters. This has practical interest since adaptive constraints are often difficult to identify directly, while they can be conveniently inferred indirectly via the easily recorded patterns of covariances between growth-based parameters. Hereafter, I provide the theoretical background of this tool, including (1) establishing the geometrical relationships between growth-based and functionally relevant parameters and (2) then specifying the correspondences between the different patterns of adaptive constraints, widening or narrowing the variations of the functional parameters and the corresponding patterns of covariations between the growth-based parameters. Illustrative examples of the practical use of this tool are provided, considering both interspecific and intraspecific variations within marine and fresh-water clams. PMID- 27398401 TI - Examining Provincial HPV Vaccination Schemes in Canada: Should We Standardise the Grade of Vaccination or the Number of Doses? AB - Human papillomavirus (HPV) infection is the most common sexually transmitted infection, which is linked to several cancers and genital warts. Depending on the Canadian province, the quadrivalent vaccine is given to girls in grades 4 through 10 with either a two- or three-dose schedule. We use a mathematical model to address the following research questions: (1) Does the grade at which the girls are vaccinated significantly affect the outcome of the program? (2) What coverage rate must the provinces reach in order to reduce the impact of HPV on the Canadian population? (3) What are the implications of vaccinating with two versus three doses? The model suggests the grade of vaccination and the number of doses do not make a significant difference to the outcome of the public vaccination program. The most significant factor is the coverage rate of children and adults. We recommend that provinces vaccinate as early as possible to avoid vaccine failure due to previous infection. We also recommend that the main focus of the program should be on obtaining a large enough coverage rate for children and/or adults in order to achieve the desired outcome with either two or three doses of the vaccine. PMID- 27398402 TI - Silk-Its Mysteries, How It Is Made, and How It Is Used. AB - This article reviews fundamental and applied aspects of silk-one of Nature's most intriguing materials in terms of its strength, toughness, and biological role-in its various forms, from protein molecules to webs and cocoons, in the context of mechanical and biological properties. A central question that will be explored is how the bridging of scales and the emergence of hierarchical structures are critical elements in achieving novel material properties, and how this knowledge can be explored in the design of synthetic materials. We review how the function of a material system at the macroscale can be derived from the interplay of fundamental molecular building blocks. Moreover, guidelines and approaches to current experimental and computational designs in the field of synthetic silklike materials are provided to assist the materials science community in engineering customized finetuned biomaterials for biomedical applications. PMID- 27398403 TI - Measurement of Fractional Exhaled Nitric Oxide as a Marker of Disease Activity in Inflammatory Bowel Disease. AB - BACKGROUND AND AIMS: Definitive diagnosis of IBD requires endoscopic and pathologic confirmation. These tools are also used to classify disease activity. Our aim was to determine if the fractional exhaled nitric oxide (FeNO) could be utilized to screen for IBD and assess for disease activity. METHODS: We matched weighted IBD cases and controls from the 2009-2010 NHANES dataset. All subjects underwent measurement of FeNO using standardized techniques. We assessed for potential confounders for FeNO measurement including age, height, and asthma. For IBD subjects, we used the presence of diarrhea, fatigue, and weight loss as a proxy for IBD activity. Laboratory parameters examined to estimate disease activity included anemia (<= 10 g/dl), iron deficiency (ferritin <= 20 ng/ml), hypoalbuminemia (<= 3.2 g/dl), and CRP (>= 1.1 mg/dl). RESULTS: The weighted sample represented 199,414,901 subjects. The weighted prevalence of IBD was 2,084,895 (1.0%). IBD subjects had nearly the same FeNO level as those without IBD (17.0 +/- 16.2 vs. 16.7 +/- 14.5 ppb). The odds of a FeNO > 25 ppb was half (OR=0.501; 95% CI 0.497-0.504) for subjects with IBD compared to those without IBD after controlling for confounders. The AUROC curve for FeNO was 0.47 (0.35 0.59). FeNO levels were not higher in patients with laboratory values suggestive of active disease. FeNO levels were higher in IBD patients with diarrhea, rectal urgency, and fatigue but were lower in those with unintentional weight loss. CONCLUSION: Measurement of FeNO does not appear to be useful to screen for IBD or assess disease activity. PMID- 27398405 TI - Ultra-High Resolution Optical Coherence Tomography Imaging of Unilateral Drusen in a 31 Year Old Woman. AB - We report a case of widespread unilateral drusen in a healthy 31 year old Caucasian woman using multi-modal imaging including ultra-high resolution optical coherence tomography (UHR-OCT). Dilated fundus exam showed multiple drusen-like lesions in the posterior pole without heme or fluid. Fundus auto fluorescence demonstrated hyperautofluorescent at the deposits. Fluorescein angiography revealed mild hyperfluorescence and staining of the lesions. Spectral-domain optical coherence tomography (SD-OCT) OS showed accumulations in the temporal macula at Bruch's membrane. UHR-OCT provided improved axial resolution compared to the standard 5 MUm on the commercial SD-OCT and confirmed the presence of deposits in Bruch's membrane, consistent with drusen. The retinal layers were draped over the excrescences but did not show any disruption. PMID- 27398404 TI - P-TEFb goes viral. AB - Positive transcription elongation factor b (P-TEFb), which comprises cyclin dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P TEFb is required for productive elongation of transcription of protein-coding genes by RNA polymerase II (pol II). In addition, P-TEFb-mediated phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P-TEFb could be effective anti-viral agents. PMID- 27398406 TI - Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction. AB - Recently there has been debate concerning the role of brain dopamine in reward and addiction. David Nutt and associates eloquently proposed that dopamine (DA) may be central to psycho stimulant dependence and some what important for alcohol, but not important for opiates, nicotine or even cannabis. Others have also argued that surfeit theories can explain for example cocaine seeking behavior as well as non-substance-related addictive behaviors. It seems prudent to distinguish between what constitutes "surfeit" compared to" deficit" in terms of short-term (acute) and long-term (chronic) brain reward circuitry responsivity. In an attempt to resolve controversy regarding the contributions of mesolimbic DA systems to reward, we review the three main competing explanatory categories: "liking", "learning", and "wanting". They are (a) the hedonic impact liking reward, (b) the ability to predict rewarding effects-learning and (c) the incentive salience of reward-related stimuli -wanting. In terms of acute effects, most of the evidence seems to favor the "surfeit theory". Due to preferential dopamine release at mesolimbic-VTA-caudate-accumbens loci most drugs of abuse and Reward Deficiency Syndrome (RDS) behaviors have been linked to heightened feelings of well-being and hyperdopaminergic states.The "dopamine hypotheses" originally thought to be simple, is now believed to be quite complex and involves encoding the set point of hedonic tone, encoding attention, reward expectancy, and incentive motivation. Importantly, Willuhn et al. shows that in a self administration paradigm, (chronic) excessive use of cocaine is caused by decreased phasic dopamine signaling in the striatum. In terms of chronic addictions, others have shown a blunted responsivity at brain reward sites with food, nicotine, and even gambling behavior. Finally, we are cognizant of the differences in dopaminergic function as addiction progresses and argue that relapse may be tied to dopamine deficiency. Vulnerability to addiction and relapse may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants and elevated stress levels. We therefore propose that dopamine homeostasis may be a preferred goal to combat relapse. PMID- 27398407 TI - A wearable artificial kidney for patients with end-stage renal disease. AB - BACKGROUND: Stationary hemodialysis machines hinder mobility and limit activities of daily life during dialysis treatments. New hemodialysis technologies are needed to improve patient autonomy and enhance quality of life. METHODS: We conducted a FDA-approved human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine, based on dialysate-regenerating sorbent technology. We aimed to determine the efficacy of the wearable artificial kidney in achieving solute, electrolyte, and volume homeostasis in up to 10 subjects over 24 hours. RESULTS: During the study, all subjects remained hemodynamically stable, and there were no serious adverse events. Serum electrolytes and hemoglobin remained stable over the treatment period for all subjects. Fluid removal was consistent with prescribed ultrafiltration rates. Mean blood flow was 42 +/- 24 ml/min, and mean dialysate flow was 43 +/- 20 ml/min. Mean urea, creatinine, and phosphorus clearances over 24 hours were 17 +/ 10, 16 +/- 8, and 15 +/- 9 ml/min, respectively. Mean beta2-microglobulin clearance was 5 +/- 4 ml/min. Of 7 enrolled subjects, 5 completed the planned 24 hours of study treatment. The trial was stopped after the seventh subject due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows. CONCLUSION: Treatment with the wearable artificial kidney was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis. These results serve as proof of concept that, after redesign to overcome observed technical problems, a wearable artificial kidney can be developed as a viable novel alternative dialysis technology. TRIAL REGISTRATION: ClinicalTrials.gov NCT02280005. FUNDING: The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc. PMID- 27398408 TI - Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells. AB - Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single cell gene expression signatures of human iPSC-derived ECs. We derived human iPSCs from 3 types of somatic cells of the same individuals: fibroblasts (FB-iPSCs), ECs (EC-iPSCs), and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into ECs by sequential administration of Activin, BMP4, bFGF, and VEGF. EC iPSCs at early passage (10 < P < 20) showed higher EC differentiation propensity and gene expression of EC-specific markers (PECAM1 and NOS3) than FB-iPSCs and CPC-iPSCs. In vivo transplanted EC-iPSC-ECs were recovered with a higher percentage of CD31+ population and expressed higher EC-specific gene expression markers (PECAM1, KDR, and ICAM) as revealed by microfluidic single-cell quantitative PCR (qPCR). In vitro EC-iPSC-ECs maintained a higher CD31+ population than FB-iPSC-ECs and CPC-iPSC-ECs with long-term culturing and passaging. These results indicate that cellular origin may influence lineage differentiation propensity of human iPSCs; hence, the somatic memory carried by early passage iPSCs should be carefully considered before clinical translation. PMID- 27398410 TI - Anti-inflammatory Function of Phyllostachys Edulis Extract in the Hippocampus of HIV-1 Transgenic Rats. AB - HIV induces neuroinflammation. We evaluated the anti-inflammatory effect of an extract from bamboo Phyllostachys edulis in the hippocampus of HIV-1 transgenic (TG) rats. Five (5) one-month-old TG rats and 5 Fisher 344 (F344) rats were fed a control diet, another 5 TG rats were fed the control diet supplemented with bamboo extract (BEX, 11 grams dry mass per 4057 Kcal). After 9 months of dietary treatment, the gene and protein expression of interleukin 1 beta (IL-1beta), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1), and the protein expression p65 and c-Jun were analyzed in the hippocampus. Compared to the F344 rats, the TG rats fed control diet showed significantly higher protein expression of GFAP and c-Jun, and mRNA and protein levels of IL-1beta. BEX supplement to the TG rats significantly lowered protein expressions of GFAP, p65, and c-Jun, and showed a trend to decrease the protein expression of IL-1beta. Compared to the TG rats, TG+BEX rats also downregulated the mRNA levels of IL-1beta and TNFalpha. In summary, neuroinflammation mediated by the NFkappaB and AP-1 pathways in the hippocampus of the TG rats was effectively abolished by dietary supplement of BEX. PMID- 27398409 TI - Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases. AB - Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein involved in matrix organization, may be involved in the pathogenesis of these diseases. We found that Fbln1 was increased in COPD patients and in cigarette smoke-induced (CS induced) experimental COPD in mice. Genetic or therapeutic inhibition of Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-alpha, IL-33, and CXCL1) in experimental COPD. Fbln1c-/- mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases. PMID- 27398411 TI - Individual motivation and threat indicators of collaboration readiness in scientific knowledge producing teams: a scoping review and domain analysis. AB - This paper identifies a gap in the team science literature that considers intrapersonal indicators of collaboration as motivations and threats to participating in collaborative knowledge producing teams (KPTs). Through a scoping review process, over 150 resources were consulted to organize 6 domains of motivation and threat to collaboration in KPTs: Resource Acquisition, Advancing Science, Building Relationships, Knowledge Transfer, Recognition and Reward, and Maintenance of Beliefs. Findings show how domains vary in their presentation of depth and diversity of motivation and threat indicators as well as their relationship with each other within and across domains. The findings of 51 indicators resulting from the review provide a psychosocial framework for which to establish a hierarchy of collaborative reasoning for individual engagement in KPTs thus allowing for further research into the mechanism of collaborative engagement. The indicators serve as a preliminary step in establishing a protocol for testing of the psychometric properties of intrapersonal measures of collaboration readiness. PMID- 27398412 TI - Involvement of Nucleophosmin (NPM1/B23) in Assembly of Infectious HPV16 Capsids. AB - We report that during assembly of HPV16 pseudovirus (PsV) the minor capsid protein, L2, interacts with the host nucleolar protein nucleophosmin (NPM1/B23). Exogenously-expressed L2 colocalized with NPM1, a complex containing both proteins could be immunoprecipitated, and L2 could redirect to the nucleus NPM1 that was pharmacologically or genetically restricted to the cytoplasm. Coexpression of the major capsid protein, L1, prevented both the colocalization and the biochemical association, and L1 pentamers could displace L2 from L2/NPM1 complexes attached to a nuclear matrix. HPV16 PsV that was produced in a cell line with reduced NPM1 levels had significantly lower infectivity compared to PsV produced in the parental cell line, although the PsV preparations had comparable L1 and L2 ratios and levels of encapsidated DNA. The PsV produced in NPM1 deficient cells showed increased trypsin sensitivity and exhibited decreased L2 levels during endocytosis. These results suggest a critical role for NPM1 in establishing the correct interactions between L2 and L1 during HPV capsid assembly. A decrease in cellular levels of NPM1 results in the formation of seemingly normal, but unstable, capsids that result in a premature loss of L2, thus inhibiting successful infection. No role for NPM1 in HPV infectious entry was found. PMID- 27398413 TI - The Establishment of an Antiviral State by Pyrimidine Synthesis Inhibitor is Cell Type-Specific. PMID- 27398414 TI - Assessing Body Fatness in Obese Adolescents: Alternative Methods to Dual-Energy X Ray Absorptiometry. PMID- 27398415 TI - A New Algorithm for Cortical Bone Segmentation with Its Validation and Applications to In Vivo Imaging. AB - Cortical bone supports and protects our skeletal functions and it plays an important in determining bone strength and fracture risks. Cortical bone segmentation is needed for quantitative analyses and the task is nontrivial for in vivo multi-row detector CT (MD-CT) imaging due to limited resolution and partial volume effects. An automated cortical bone segmentation algorithm for in vivo MD-CT imaging of distal tibia is presented. It utilizes larger contextual and topologic information of the bone using a modified fuzzy distance transform and connectivity analyses. An accuracy of 95.1% in terms of volume of agreement with true segmentations and a repeat MD-CT scan intra-class correlation of 98.2% were observed in a cadaveric study. An in vivo study involving 45 age-similar and height-matched pairs of male and female volunteers has shown that, on an average, male subjects have 16.3% thicker cortex and 4.7% increased porosity as compared to females. PMID- 27398416 TI - Energy harvesting from human motion: materials and techniques. AB - Energy harvesting from human motion is a research field under rapid development. In this tutorial review we address the main physical and physico-chemical processes which can lead to energy generation, including electromagnetism, piezoelectricity, and electrostatic generation. Emphasis is put on the relationships among material properties and device efficiency. Some new and relatively less known approaches, such as triboelectric nanogeneration (TENG) and reverse electrowetting (REWOD), are reported in more detail. PMID- 27398417 TI - Could plants have cognitive abilities? AB - Vegetation is traditionally regarded as passive, doing nothing but what is essential to grow and survive. Evidence is accumulating, however, in support of formerly esoteric notions that plants can communicate, remember, even count- features that one would call cognitive if they were observed in animals. Michael Gross reports. PMID- 27398418 TI - Gordon Fain. PMID- 27398419 TI - Murder, Sex, Neonates, and Other Forays into Bioethics. PMID- 27398421 TI - Prof. Luis Diaz and the Early Days of Solid State NMR in Argentina - Recollections from his First Graduate Student. PMID- 27398420 TI - A Message from the ABFM President. PMID- 27398422 TI - Preface. PMID- 27398423 TI - Preface. PMID- 27398424 TI - Preface - Special Issue "Mini-Reviews in Medicinal Chemistry" Proceedings of the Twentieth Anniversary of the Faculty of Pharmacy of the University of Calabria. PMID- 27398426 TI - Measuring the impact of a pharmacist in the intensive care unit-are all pharmacists created equal? PMID- 27398425 TI - [Not Available]. PMID- 27398427 TI - Response to the Letter to the Editor regarding "Feasibility, safety, and outcome of very early enteral nutrition in critically ill patients: Results of an observational study". PMID- 27398428 TI - Seeking NP jobs for NPs. PMID- 27398429 TI - What makes a Maori nurse unique? PMID- 27398430 TI - Synergistic Nanomedicine: Passive, Active, and Ultrasound-Triggered Drug Delivery in Cancer Treatment. AB - Nanocarriers are heavily researched as drug delivery vehicles capable of sequestering antineoplastic agents and then releasing their contents at the desired location. The feasibility of using such carriers stems from their ability to produce a multimodel delivery system whereby passive, ligand and triggered targeting can be applied in the fight against cancer. Passive targeting capitalizes on the leaky nature of tumor tissue which allows for the extravasation of particles with a size smaller than 0.5 um into the tumors. Ligand targeting utilizes the concept of receptor-mediated endocytosis and involves the conjugation of ligands onto the surface of nanoparticles, while triggered targeting involves the use of external and internal stimuli to release the carriers contents upon reaching the diseased location. In this review, micelles and liposomes have been considered due to the promising results they have shown in vivo and in vitro and their potential for advancements into clinical trials. Thus, this review focuses on the most recent advancements in the field of micellar and liposomal drug delivery and considers the synergistic effect of passive- and ligand-targeting strategies, and the use of ultrasound in triggering drug release at the tumor site. PMID- 27398431 TI - Tubular Tissues and Organs of Human Body--Challenges in Regenerative Medicine. AB - Tissue engineering of tubular organs such as the blood vessel, trachea gastrointestinal tract, urinary tract are of the great interest due to the high amount of surgeries performed annually on those organs. Development in tissue engineering in recent years and promising results, showed need to investigate more complex constructs that need to be designed in special manner. Stent technology remain the most widely used procedure to restore functions of tubular tissues after cancer treatment, or after organ removal due to traumatic accidents. Tubular structures like blood vessels, intestines, and trachea have to work in specific environment at the boundary of the liquids, solids or air and surrounding tissues and ensure suitable separation between them. This brings additional challenges in tissue engineering science in order to construct complete organs by using combinations of various cells along with the support material systems. Here we give a comprehensive review of the tubular structures of the human body, in perspective of the current methods of treatment and progress in regenerative medicine that aims to develop fully functioning organs of tubular shape. Extensive analysis of the available literature has been done focusing on materials and methods of creations of such organs. This work describes the attempts to incorporate growth factors and drugs within the scaffolds to ensure localized drug release and enhance vascularization of the organ by attracting blood vessels to the site of implantation. PMID- 27398432 TI - Nanomaterial Induced Immune Responses and Cytotoxicity. AB - Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. PMID- 27398433 TI - Technologies and Applications in Micro-Volume Liquid Handling. AB - Micro-volume liquid handling technologies have been extensively used in the field of molecular biology and have been under rapid development over the last several decades. Accompanying the trend of laboratory automation and high-throughput, the liquid dispensing is increasingly playing an important role in protein crystallization, drug screening and DNA sequencing, and it also needs to satisfy the exacting requirements, such as the higher processing speed, higher pipetting precision and lower processing costs. The purpose of this review is to provide an overview of micro-volume liquid-handling technology and summarize the latest applications of this technology. Finally, some future trends and perspectives in these research areas will be outlined. PMID- 27398434 TI - Advanced Gold Nanomaterials for Photothermal Therapy of Cancer. AB - Photothermal therapy represents a non-invasive therapeutic tool to eradicate cancer tumor with minimum toxic effects. In this ablative therapy, accurate delivery of efficient photothermal conversion agents followed by laser irradiation results in tumor ablation with lower toxicity compared to other cancer therapies. Gold nanomaterials are efficient to passively target and deliver photothermal agents to the cancer tumor. Through surface plasma resonance, gold nanomaterials including nanorods, nanostars, nanoflowers, nanocages and nanoshells exhibited strong NIR absorption and are widely utilized during photothermal ablative therapy of cancer. Currently, researchers have devoted their attention to minimize toxicity of photothermal agents using modified probe design. By developing this noninvasive cancer therapy, expectations to minimize toxicity of cancer treatment may become reality sooner. PMID- 27398435 TI - Nanoencapsulation of the Bioactive Compounds of Spirulina with a Microalgal Biopolymer Coating. AB - Microalgae have been studied in biotechnological processes due to the various biocompounds that can be obtained from their biomasses, including pigments, proteins, antioxidants, biopeptides, fatty acids and biopolymers. Microalgae biopolymers are biodegradable materials that present similar characteristics to traditional polymers, with the advantage of being rapidly degraded when discarded. In addition, nanoencapsulation is capable of increasing the availability of bioactive compounds by allowing the release of these biocompounds to occur slowly over time. The use of polymers in the nanoencapsulation of active ingredients can mask the undesired physicochemical properties of the compounds to be encapsulated, thereby enhancing consumer acceptability. This covering also acts as a barrier against several foreign substances that can react with bioactive compounds and reduce their activity. Studies of the development of poly 3-hydroxybutyrate (PHB) nanocapsules from microbial sources are little explored; this review addresses the use of nanotechnology to obtain bioactive compounds coated with biopolymer nanocapsules, both obtained from Spirulina biomasses. These microalgae are Generally Recognized as Safe (GRAS) certified, which guarantees that the biomass can be used to obtain high added value biocompounds, which can be used in human and animal supplementation. PMID- 27398436 TI - Physiological Interactions of Nanoparticles in Energy Metabolism, Immune Function and Their Biosafety: A Review. AB - Nanoparticles owing to their unique physico-chemical properties have found its application in various biological processes, including metabolic pathways taking place within the body. This review tried to focus the involvement of nanoparticles in metabolic pathways and its influence in the energy metabolism, a fundamental criteria for the survival and physiological activity of living beings. The human body utilizes energy derived from food resources through a series of biochemical reactions involving several enzymes, co-factors (metals, non-metals, vitamins etc.) through the metabolic pathways (glycolysis, tri carboxylic acid cycle, oxidative phosphorylation, electron transport chain, etc.) in cellular system. Energy metabolism is also involved in the immune networking of the body for self defence and against pathophysiology. The immune system comprises of different cells and tissues, bioactive molecules for self defence and to fight against diseases. In the recent times, it has been reported through in vivo and in vitro studies that nanoparticles have direct influence on body's immune functions, and can modulate immunity by either suppressing or enhancing it. A comprehensive overview of nanoparticles and its involvement in immune function of the body in normal and pathophysiological conditions has been discussed. Considering these perspectives on nanoparticle interaction another important area which has been highlighted is the biosafety issues which are necessary before therapeutic applications. It is expected that development of physiologically compatible nanoparticles controlling energy metabolic processes, immune functions may show new dimension in the pathophysiology linked with energy and immunity. PMID- 27398437 TI - Zirconium Phosphate Nanoplatelet Potential for Anticancer Drug Delivery Applications. AB - Zirconium phosphate (ZrP) nanoplatelets can intercalate anticancer agents via an ion exchange reaction creating an inorganic delivery system with potential for cancer treatment. ZrP delivery of anticancer agents inside tumor cells was explored in vitro. Internalization and cytotoxicity of ZrP nanoplatelets were studied in MCF-7 and MCF-10A cells. DOX-loaded ZrP nanoplatelets (DOX@ZrP) uptake was assessed by confocal (CLSM) and transmission electron microscopy (TEM). Cytotoxicity to MCF-7 and MCF-10A cells was determined by the MTT assay. Reactive Oxy- gen Species (ROS) production was analyzed by fluorometric assay, and cell cycle alterations and induction of apoptosis were analyzed by flow cytometry. ZrP nanoplatelets were localized in the endosomes of MCF-7 cells. DOX and ZrP nanoplatelets were co-internalized into MCF-7 cells as detected by CLSM. While ZrP showed limited toxicity to MCF-7 cells, DOX@ZrP was cytotoxic at an IC50 similar to that of free DOX. Meanwhile, DOX lC50 was significantly lower than the equivalent concentration of DOX@ZrP in MCF-10A cells. ZrP did not induce apoptosis in both cell lines. DOX and DOX@ZrP induced significant oxidative stress in both cell models. Results suggest that ZrP nanoplatelets are promising as carriers of anticancer agents into cancer cells. PMID- 27398438 TI - Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-Mercaptopropionic Acid and CdTe-Mercaptosuccinic Acid Quantum Dots. AB - CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining. PMID- 27398439 TI - Surface Functionalized Graphene Biosensor on Sapphire for Cancer Cell Detection. AB - Graphene has several unique physical, optical and electrical properties such as a two-dimensional (2D) planar structure, high optical transparency and high carrier mobility at room temperature. These make graphene interesting for electrical biosensing. Using a catalyst-free chemical vapor deposition (CVD) method, graphene film is grown on a sapphire substrate. There is a single or a few sheets as confirmed by Raman spectroscopy and atomic force microscopy (AFM). Electrical graphene biosensors are fabricated to detect large-sized biological analytes such as cancer cells. Human colorectal carcinoma cells are sensed by the resistance change of an active bio-functionalized graphene device as the cells are captured by the immobilized antibody surface. The functionalized sensors show an increase in resistance as large as ~20% of the baseline with a small number of adhered cells. This study suggests that the bio-functionalized electrical graphene sensors on sapphire, which is a highly transparent material, can potentially detect circulating tumor cells (CTCs) and monitor cellular electrical behavior while being compatible with fluorescence-based optical-detection bioassays. PMID- 27398440 TI - Enhanced Germicidal Efficacy by Co-Delivery of Validamycin and Hexaconazole with Methoxy Poly(ethylene glycol)-Poly(lactide-co-glycolide) Nanoparticles. AB - Co-delivery system has been proposed in pharmaceutical field aim to synergistic treatments. The combination formulation is also important in traditional pesticides formulations based on the low pest resistance risk and wide fungicidal spectrum. However, co-delivery nanoparticles (NPs) tend to be more environmentally friendly for the sustained-release behaviour and none of toxic organic solvents or dusts. Hence, we constructed co-delivery NPs which could delivery two kinds of pesticides, which function was similar with pesticides combination formulation. The co-delivery NPs of validamycin and hexaconazole were prepared with the amphiphilic copolymer methoxy poly(ethylene glycol)- poly(lactide-co-glycolide) (mPEG-PLGA) used an improved double emulsion method. The chemical structure of mPEG-PLGA copolymer was confirmed using fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR). The co-delivery NPs all exhibited good size distribution and held sustained-release property. Germicidal efficacy of the co-delivery NPs against Rhizoctonia cerealis was also studied. The germicidal efficacy of co delivery NPs against Rhizoctonia cerealis was better than that of traditional pesticides formulation. In addition, co-delivery NPs showed a lasting impact against Rhizoctonia cerealis. PMID- 27398441 TI - Paclitaxel-Loaded TPGS-b-PCL Nanoparticles: In Vitro Cytotoxicity and Cellular Uptake in MCF-7 and MDA-MB-231 Cells versus mPEG-b-PCL Nanoparticles and Abraxane(r). AB - Nanomedicines have become an attractive platform for the development of novel drug delivery systems in cancer chemotherapy. Polymeric nanoparticles (NPs) represent one of the best well-investigated nanosized carriers for delivery of antineoplastic compounds. The "Pegylation strategy" of drug delivery systems has been used in order to improve carrier biodistribution, however, some nanosized systems with PEG on their surface have exhibited poorly-cellular drug internalization. In this context, the purpose of the present study was to compare in vitro performance of two paclitaxel (PTX)-loaded NPs systems based on two biocompatible copolymers of alpha tocopheryl polyethylene glycol 1000 succinate block-poly(epsilon-caprolactone) (TPGS-b-PCL) and methoxyPEG- block-poly(epsilon caprolactone) (mPEG-b-PCL) in terms of citotoxicity and PTX cellular uptake. Fur- thermore, TPGS-b-PCL NPs were also copared with the commercially available PTX nano-sized formulation Abraxane(r). Both TPGS-b-PCL and mPEG-b-PCL derivates were synthesized by ring opening polymerization of epsilon-caprolactone employing microwaved radiation. NPs were obtained by a solvent evaporation technique where the PTX content was determined by reverse-phase HPLC. The resulting NPs had an average size between 200 and 300 nm with a narrow size distribution. Also both NPs systems showed a spherical shape. The in vitro PTX release profile from the NPs was characterized employing the dialysis membrane method where all drug loaded formulations showed a sustained and slow release of PTX. Finally, in vitro assays demonstrated that PTX-loaded TPGS- b-PCL exhibited a significant higher antitumor activity than PTX-loaded mPEG-b-PCL NPs and Abraxane(r) against an estrogen-dependent (MCF-7) and an estrogen independent (MDA-MB-231) breast cancer cells lines. Furthermore TPGS-b-PCL NPs showed a significant increase on PTX cellular uptake, for both breast cell lines, in comparison with mPEG-b-PCL NPs and Abraxane(r). Overall findings confirmed that NPs based on TPGS-b-PCL as biomaterial demonstrated a better in vitro performance than NPs with PEG, representing an attractive alternative for the development of novel nanosized carriers for anticancer therapy. PMID- 27398442 TI - Photodynamic Therapy with Hexa(sulfo-n-butyl)[60]Fullerene Against Sarcoma In Vitro and In Vivo. AB - The hydrophilic molecular micellar hexa(sulfo-n-butyl)[60]fullerene (FC4S), first synthesized in 1998 as a photosensitizer (PS) has been reported to exhibit high efficacy for singlet oxygen generation and antimicrobial photodynamic inactivation. The purpose of this study was to investigate the effects of photoactivated FC4S for free radical generation and to mediate photodynamic therapy (PDT) of cancer in vitro and in vivo. The results demonstrated that following light irradiation, FC4S produced singlet oxygen, but after addition of electron donors such as ferrocytochrome c or NADH, FC4S also produced superoxide. The combination of FC4S with light irradiation was able to induce cytotoxicity to human fibrosarcoma cells and murine sarcoma 180 cells in vitro. Cell-killing was proportional to fluence as well as FC4S concentration. Photoirradiation by argon ion laser after intraperitoneal injection of FC4S also resulted in inhibition of S180 tumor growth in vivo (up to 80% reduction of tumor volume). Hematological and blood biochemistry parameters of the cancer-bearing mice were improved by PDT. Based on these findings, we conclude that FC4S has a great potential as a nanomedicine in PDT for cancer. PMID- 27398443 TI - Immobilization and Characterization of Penicillin G Acylase (PGA) Immobilized on Magnetic Ni0.5Zn0.5Fe2O4 Nanoparticles. AB - Magnetic Ni0.5Zn0.5Fe2O4 nanoparticles were prepared via the solution combustion process and their microstructure and magnetic properties were investigated by X ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The as-prepared magnetic Ni0.5Zn0.5Fe2O4 nanoparticles are characterized with average grain size of about 20 nm and magnetization of 90.3 Am2/kg. The surface of magnetic Ni0.5Zn0.5Fe2O4 nanoparticles was modified by use of sodium silicate and N-(3 Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, and the penicillin G acylase (PGA) was successfully immobilized on the surface-modified magnetic Ni0.5Zn0.5Fe2O4 nanoparticles. The results show that the activity for the immobilized PGA is affected less by pH and temperature than that for the free PGA, and the immobilized PGA exhibits a high effective activity, good stability of enzyme catalyst. This immobilized PGA on magnetic Ni0.5Zn0.5Fe2O4 nanoparticles can be separated from the solution by the external magnetic field for cyclic utilization, and they could retain about 70% of initial enzyme activity after 11 consecutive operations. The kinetic parameters (Km and Vmax) were determined, and the value of Km for the immobilized PGA (204.53 mmol/L) is higher than that of the free enzyme (3.50 mmol/L), while Vmax (1.93 mmol/min) is also larger than that of the free enzyme (0.838 mmol/min). PMID- 27398444 TI - Folic Acid-Functionalized Polythiophene for Targeted Cellular Imaging. AB - Polythiophene containing pendant N-hydroxysuccinimide (NHS) ester groups was reacted with poly(ethylene glycol) (PEG) and oleylamine, which was subsequently modified with folic acid to prepare a targeting fluorescent cellular imaging probe. The amphiphilic character of the folic acid-functionalized polythiophene induced the formation of nanoparticles with an average diameter of 95.3 nm in water. This polymer shows good photostability and low toxicity toward KB cells at a high concentration (100 ug/mL), which meets the crucial requirement for cellular imaging and other biological applications. The folic acid-functionalized polythiophene could be internalized efficiently into KB cells and accumulated in the cytoplasm to yield bright fluorescence, indicating that it is a good candidate material for the fluorescence imaging of living cells. PMID- 27398445 TI - Molecular Imaging of CD44-Overexpressing Gastric Cancer in Mice Using T2 MR Imaging. AB - Novel diagnostic techniques have been developed in many research area using targetable contrast agents with magnetic resonance imaging (MRI) for cancer diagnosis. For cancer diagnosis, the use of MRI with biocompatible targeting moieties and manganese ferrite nanoparticles (MFNPs) is preferred. Thus, we synthesized MFNPs using a thermal decomposition method which enables sensitive T2 or T2 Turbo Spin Echo (TSE) MRI and coated them with hyaluronic acid (HA). The high targeting ability of HA-MFNPs was observed at MKN-45 cells (gastric cancer cell line) which high-expressing CD44 in contrast with MKN-28 cells which low expressing CD44. We also prepared the gastric cancer mice model using MKN-45 cells which has the stem-like property was implanted into BALB/c nude mice. And then HA-MFNPs of the T2 contrast enhancement effects and targeting ability were investigated by in vivo MR imaging. As a result of these studies, we conclude that HA coated MFNPs can be effectively used as a novel probes for visualizing gastric cancer stem cells. PMID- 27398446 TI - Cytotoxic Effect of Lipophilic Bismuth Dimercaptopropanol Nanoparticles on Epithelial Cells. AB - Bismuth nanoparticles have many interesting properties to be applied in biomedical and medicinal sectors, however their safety in humans have not been comprehensively investigated. The objective of this research was to determine the cytotoxic effect of bismuth dimercaptopropanol nanoparticles (BisBAL NPs) on epithelial cells. The nanoparticles are composed of 18.7 nm crystallites on average and have a rhombohedral structure, agglomerating into chains-like or clusters of small nanoparticles. Based on MTT viability assay and fluorescence microscopy, cytotoxicity was not observed on monkey kidney cells after growing with 5 uM of BisBAL NPs for 24 h. Employing same techniques, identical results were obtained with human epithelial cells (HeLa), showing a not strain-dependent phenomenon. The absence of toxic effects on epithelial cells growing with BisBAL NPs was corroborated with long-time experiments (24-72 hrs.), showing no difference in comparison with growing control (cells without nanoparticles). Further, genotoxicity assays, comet assay and fluorescent microscopy and electrophoresis in bromide-stained agarose gel revealed no damage to genomic DNA of MA104 cells after 24 h. of exposition to BisBAL NPs. Finally, the effect of bismuth nanoparticles on protein synthesis was studied in cells growing with BisBAL NPs for 24 h. SDS-PAGE assays showed no difference between treated and untreated cells, suggesting that BisBAL NPs did not interfere with protein synthesis. Hence BisBAL NPs do not appear to exert cytotoxic effects suggesting their biological compatibility with epithelial cells. PMID- 27398447 TI - Cytotoxic Effects of ZnO Nanoparticles on the Expression of ROS-Responsive Genes in the Human Cell Lines. AB - In the present investigation, engineered ZnO nanoparticles were tested for their induced oxidative stress in T47D tumor cell lines. The expressions of reactive oxygen species (ROS) related genes, glutathione S-transferase (GST) and catalase were quantified by real time-polymerase chain reaction (RT-PCR). In addition, qualitative analysis of GST was also performed at the cell level using molecular beacon (MB) technology. The tested nanoparticles were 20 nm in size, water dispersible and treated on human breast tumor epithelial cell lines at 20, 40, 80 ug/ml concentration with 14, 28, 48 h incubation times. Nanoparticles induced expressions of ROS responsive genes at molecular and cellular level, produces consistent results with respect to different dosage and incubation time. The experiment showed that the expression of both GST and catalase genes were maximized at 28 h with 80 ug/ml concentration. However, the toxic effect of the monodisperse ZnO nanoparticles was not significant compared with control experiments, demonstrating its high potential in the applications of nanomedicines for a diagnostic and therapeutic tool. PMID- 27398448 TI - In Vitro Uptake of Silver Nanoparticles and Their Toxicity in Human Mesenchymal Stem Cells Derived from Bone Marrow. AB - During the last decade, the usage of silver nanoparticles in biomedical fields has increased rapidly, mainly due to their excellent antibacterial effects. They are used in many medical products such as wound dressings, catheters, bone cement and artificial cardiac valves. In tissue engineering, silver nanoparticles are often loaded as a filler for fabrication of nanocomposite scaffolds which subsequently are seeded with human mesenchymal stem cells. Thus, possible adverse effects of silver nanoparticles on human stem cells should be investigated carefully to ensure a safe usage. In this study, silver nanoparticles with a mean diameter of ~30 nm were prepared and their toxicity in human mesenchymal stem cells was investigated. Transmission electron microscopic images reveal the uptake and localization of the silver nanoparticles in the cytoplasm. Upon internalization of Ag NPs inside the cells, an increase in the release of lactate dehydrogenase and the production of reactive oxygen species was quantified. Furthermore, they caused a reduction in both cell viability and mitochondrial membrane potential in a dose-dependent manner. Annexin V-FITC/PI staining implied that silver nanoparticles did not only induce apoptosis but also cause necrosis. Based on cell cycle analysis, G2/M arrest was detected in cells treated with silver nanoparticles, implicating DNA damage. The high level of reactive oxygen species induced by nanoparticles is considered to be the main cause of their toxicity. PMID- 27398449 TI - Chitosan Tethered Colloidal Gold Nanospheres for Drug Delivery Applications. AB - Gold Nanospheres (AuNS) have been widely explored as an emerging system for various biomedical applications including drug delivery, bioimaging and photomedicine. However, method of synthesizing nanoparticles and its toxicity including bioaccumulation has been a problem of concern. In the present study, we explored the appropriateness of 12.0 +/-1.99 nm chitosan reduced AuNS in vivo models with respect to its bioavailability and toxicity against various concentrations (2.5-7.5 mg/kg). Administration of AuNS did not show any signs of morbidity. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis of blood (0.156 +/- 0.154), urine (0.084 +/- 0.08) and tissues indicates gradual dissipation and obligatory clearance within 24 h time interval. Nevertheless, pres- ence of AuNS in blood after 24 h confirms the bioavailability of AuNS demonstrating the evidence for no immune clearance and efficient tissue uptake. Further, brain shows the lowest quantity of injected AuNS. From this result, we determine this chitosan monolayer protected AuNS could cross the blood brain barrier and enter to the neural tissues. Interestingly there was no evidence of toxicity in any of the organs. In conclusion, our data suggest that AuNS injected though tail vain were easily taken up by tissues and does not produce sub-acute physiological damage even at high concentrations tested, supporting chitosan reduced AuNS as biocompatible, nontoxic nanoconjugates for targeted drug delivery and other biomedical applications. PMID- 27398450 TI - Preparation and Drug-Delivery Properties of HKUST-1/GO Hybrid. AB - A hybrid HKUST-1/GO composite was synthesized and its drug loading and drug release abilities were investigated. The adsorption of IBU (ibuprofen) onto the surface of HKUST-1/GO and HKUST-1 composites was compared, and it was found that the addition of GO enhanced both IBU loading and stability. The addition of GO also enhanced the specific surface area. Drug release experiments on IBU loaded HKUST-1 and HKUST-1/GO were conducted, and it was found that drug release of HKUST-1/GO was slower, which can be explained by the hydrogen bonding between GO and IBU. It can be concluded that the addition of GO not only enhances drug loading, but can also achieve a more desirable slow-release of the drug. PMID- 27398451 TI - Synthesis and Evaluation of Thermo-Sensitive, Magnetic Fluorescent Nanocomposite as Trifunctional Drug Delivery Carrier. AB - The thermo-sensitive magnetic fluorescent trifunctional nanocomposite (Fe3O4/ZnS@PNIPAM) has been synthesized via a facile route. The obtained biocompatible nanocomposite was composed of monodisperse heterostructural Fe3O4/ZnS core and a thermo-sensitive poly(N-isopropyl acrylamide) (PNIPAM) shell. Fe3O4/ZnS acted as magnetic response and fluorescence luminous body, PNIPAM acted as drug loaded platform which can adsorb and release drug controllably. Fe3O4/ZnS@PNIPAM was characterized and all of the results showed that it had excellent magnetic response, photostability and thermo-sensitivity. Moreover, the drug release studies in vitro showed that the release rate increased with increasing temperature. MTT assays in model HepG2 cells demonstrated that Fe3O4/ZnS@PNIPAM was practically non-toxic. Thus, our results revealed that Fe3O4/ZnS@PNIPAM would be used in biomedical fields such as targeted drug delivery, as well as cancer diagnosis and treatment in the nearly future. PMID- 27398452 TI - Development of Novel Polymer-Lipid Hybrid Nanoparticles of Tamoxifen: In Vitro and In Vivo Evaluation. AB - This study was undertaken to develop and investigate the effect of tamoxifen polymer-lipid hybrid nanoparticles (Tmx-PLN) on its oral bioavailability and efficacy in the 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model. Modified solvent emulsification-evaporation method was optimized to obtain Tmx PLN, composed of chitosan and lecithin, of 169.66 +/- 4.84 nm particle size. The PLN exhibited prolonged in vitro release in phosphate-buffered saline. Further, PLN displayed enhanced oral bioavailability with considerable increase in AUC (1277.46 vs. 585.01 ng/ml . h), pro- longed t1/2 (27.87 +/- 15.62 vs. 10.18 +/- 6.5 h) and mean residence time (40.11 +/- 25.72 vs. 17.42 +/- 12.04 h) in comparison to pure Tmx. In addition, PLN exhibited significantly increased (P < 0.05) antitumor efficacy in DMBA-induced breast cancer model, when administered once in three days in comparison to Tmx daily dosing. This enhancement may be attributed to a probable reduction in Pgp efflux, decreased first-pass metabolism and lymphatic drug transport. Thus, Tmx-PLN exhibited enhanced potential to increase Tmx therapeutic efficacy in chronic treatment of breast cancer. PMID- 27398453 TI - Neuroprotective Potential of Superparamagnetic Iron Oxide Nanoparticles Along with Exposure to Electromagnetic Field in 6-OHDA Rat Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the dopaminergic neurons of the substantia nigra leading to various motor and non-motor deficits. We explored the neuroprotective potential of superparamagnetic iron oxide nanoparticles (IONPs) along with exposure to EMF in 6-OHDA rat model of PD. IONPs were implanted at the site of lesion and 24 h thereafter the rats were exposed to magnetic fields 2 h/day for one week. Bilateral lesions of the striatum were made with 6-OHDA. The rats in all the intervention groups improved progressively over the days and by post-surgery day 4 they were active and bright. We observed a significant beneficial effect of the IONPs implantation and MF exposure on feeding behavior, gait and postural stability. There was a significant enhancement of mitochondrial function and attenuation of lesion volume in all the intervention groups as compared to PD. The results demonstrate neuroprotective effect of iron oxide nanoparticle implantation and magnetic field exposure in an in vivo 6-OHDA rat model of PD. PMID- 27398454 TI - Dendritic Cells Stimulated by Cationic Liposomes. AB - Immunotherapy of cancer aims to harness the immune system to detect and destroy cancer cells. To induce an immune response against cancer, activated dendritic cells (DCs) must present tumor antigens to T lymphocytes of patients. However, cancer patients' DCs are frequently defective, therefore, they are prone to induce rather tolerance than immune responses. In this context, loading tumor antigens into DCs and, at the same time, activating these cells, is a tempting goal within the field. Thus, we investigated the effects of cationic liposomes on the DCs differentiation/maturation, evaluating their surface phenotype and ability to stimulate T lymphocytes proliferation in vitro. The cationic liposomes composed by egg phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium propane and 1,2-dioleoylphosphatidylethanolamine (50/25/25% molar) were prepared by the thin film method followed by extrusion (65 nm, polydispersity of 0.13) and by the dehydration-rehydration method (95% of the population 107 nm, polydispersity of 0.52). The phenotypic analysis of dendritic cells and the analysis of T lymphocyte proliferation were performed by flow cytometry and showed that both cationic liposomes were incorporated and activated dendritic cells. Extruded liposomes were better incorporated and induced higher CD86 expression for dendritic cells than dehydrated-rehydrated vesicles. Furthermore, dendritic cells which internalized extruded liposomes also provided stronger T lymphocyte stimulation. Thus, cationic liposomes with a smaller size and polydispersity seem to be better incorporated by dendritic cells. Hence, these cationic liposomes could be used as a potential tool in further cancer immunotherapy strategies and contribute to new strategies in immunotherapy. PMID- 27398455 TI - In Vitro Osteogenic Differentiation Enhanced by Zirconia Coated with Nano-Layered Growth and Differentiation Factor-5. AB - Zirconia (Zr) is also known as a biocompatible material with favorable mechanical properties as well as low plaque adhesion. In this study, we examined the efficacy of Zr coated with growth and differentiation factor-5 (GDF-5) bonded via click reaction as a substrate to support osteogenic differentiation of MC3T3-E1 cells. Pristine and surface-modified Zr surfaces were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), resulting that GDF-5 was successfully coated to the pristine Zr surface. GDF-5 coated to Zr surfaces was released for 28 days in a sustained manner. New bone formation onto GDF-5 coated Zr (Zr/GDF-5) surface was confirmed by in vitro test including cell proliferation, alkaline phosphatase activity and calcium deposition assays, and in vivo test including real-time polymerase chain reaction (qPCR) assay including osterix (OSX), runt-related transcription factor 2 (Runx 2), COL 1 (type I collagen) and osteocalcin (OC). Cell proliferation, alkaline phosphatase activity, and calcium deposition of MC3T3- E1 cells were significantly enhanced when the cells were cultured on Zr/GDF-5. Additionally, the results of qPCR revealed that genes related with osteogenic differentiation were up regulated when the cells were cultured on Zr/GDF-5. Our findings demonstrate that Zr/GDF-5 could be used as a material for enhancing the efficacy of osteogenic differentiation. PMID- 27398456 TI - Chemical Vapor Deposited Few-Layer Graphene as an Electron Field Emitter. AB - Chemical vapor deposition (CVD) growth of graphene on polycrystalline copper (Cu) foil in a low pressure conditions has been presented, aiming to achieve the highest quality with large-scale fabrications, which requires comprehensive understanding and effective controlling of the growth process. Herein, few-layer graphene (FLG) films with large-domain sizes were grown on Cu metal catalyst substrates using a vertical mass-flow hot-filament CVD reactor, with the intention of large scale production, by optimizing the CVD system and three of the process parameters: (i) gas flow compositions, (ii) substrate annealing time and (iii) graphene deposition time. The detailed scanning electron microscope and Raman spectroscopy analysis indicate that all the above mentioned process parameters affect growth of FLG film on Cu substrate. The presence of two intense peaks, G and 2D-band at 1583.6 and 2702.6 cm-1 for synthesized sample at optimized conditions (H2/CH4 ratio of 50:1 at graphene deposition time of 10 minutes and substrate annealed time for 20 minutes) revealed the formation of FLG films with large domain size. These graphene films on Cu have shown the room temperature field electron emission characteristics, hence appears to be prospective candidate for vacuum nanoelectronics. PMID- 27398457 TI - Kinetics of Photocatalytic Degradation of Methylene Blue by TiO2-Graphene Nanocomposites. AB - Reduced graphene oxide (RGO)/TiO2 nanocomposite was successfully prepared by UV assisted photocatalytic reduction of graphene oxide (XGO) by TiO2 nanoparticles in ethanol. The effects of XGO and RGO addition in TiO2were characterized by transmission electron microscopy (TEM), X-ray diffractometer (XRD), diffuse reflectance UV-vis spectrophotometer (UV-vis), fourier-transform infrared spectroscopy (FTIR), photoluminescence (PL), and Brunauer-Emmett-Teller (BET) and Barrett-Joiner-Halenda (BJH) porosity analysis. The photocatalytic activity of prepared nanocomposites was evaluated from the kinetics of the photocatalytic degradation of cationic methylene blue dye under UV irradiation. Bandgap, the electron-hole recombination, specific surface area, surface functional groups, and adsorption capacity of nanocomposites were found to play a significant role in the degradation. The results revealed that RGO/TiO2 and XGO/TiO2 nanocomposites exhibited efficient charge separation and enhanced photocatalytic activity, compared to pristine TiO2. Nearly 500% improvement was observed in this work. PMID- 27398458 TI - Graphene/Nickel Nanofiber Hybrids for Catalytic and Microbial Fuel Cell Applications. AB - The present work deals with the preparation of fcc-nickel (Ni) nanofibers and Graphene/Ni hybrids. The analysis of XRD, FTIR and Raman data confirms the formation of pure Ni, graphite oxide, reduced graphene and their hybrids. SEM micrographs clearly show the decoration of Ni nanofibers on the graphene flakes. The synthesized Ni-based hybrid systems can have applications in areas ranging from: magnetism, catalysis to microbial fuel cells. The vibrating sample magnetometer (VSM) investigations reveal that the hybrid structure shows hysteresis loop similar to that expected from a superparamagnetic system. When the same hybrid structure is used as catalyst for decolourization of 4 nitrophenol, the maximum rate constant of 0.1 min-1 can be obtained. The catalytic activity also shows dependence on the loading concentration of Ni. The enhanced performance can be explained on the basis of synergistic effect between graphene and nickel nanofibers. The developed hybrids have also been applied as catalyst for cathode in microbial fuel cells and the studies showed improved power density compared to conventional microbial fuel cells (MFCs). PMID- 27398459 TI - Substrate Considerations for the Formation of the Graphene-CNTs Hybrid on the Dielectric Substrate. AB - Graphene-carbon nanotube (CNT) hybrid materials are directly synthesized on an unpolished SiO2 substrate by the use of a chemical vapor deposition (CVD) system with a two-temperature reactor. The two-temperature reactor utilized here proves more efficient than that of the one-temperature reactor. Potential candidate substrates for the formation of the graphene-CNT hybrid materials are discussed in detail. SEM and Raman results demonstrate that the unpolished SiO2 base is the most fitting substrate for the graphene-CNT hybrid CVD growth. These results open the way for direct and high-efficiency production of graphene-CNT hybrid materials with high conductivity and transmittance. PMID- 27398460 TI - In Situ Hydrothermal Synthesis of Graphene-CuO Nanocomposites for Lithium Battery Applications. AB - Graphene-CuO nanocomposites were prepared by in situ hydrothermal method. The properties of the prepared nanocomposites have been studied by XRD, SEM, TEM, TGA, FT-IR, TGA and CV technqiues. The prepared nanocomposites show uniform dispersion of CuO nanoparticles in between the graphene sheets. The interlayer spacing of the graphene sheets has been increased due to the inclusion of CuO nanoparticles as revealed by TEM analysis. The modification in the interlayer spacing and the CuO functionalization in between the layers would be useful in designing high performance lithium ion battery electrodes. PMID- 27398461 TI - Study of Oxidation States with Heating on Charge Transport of the Graphene Nanoribbon. AB - In this paper, we present a study based on extended Huckel (ETH) and the Green function of the electron transport in a graphenenanoribbon with a nanopore oxidized in the middle. We con- sider several types of oxidation:hydroxyl, carboxyl and ketone groups adsorbed in edges, pore and surface of the riddon. The results indicate that nanoribbons with medium and high oxidation are more thermally stable than the low oxidation nanoribon that shows greater sensitivity at 120 degrees C. Finally, Ohmic and Negative Differential Resistance (NDR) were obtained from I(V) curves, thus was possible determine the current peaks and threshold voltages (V(Th1) < V(Th2) < V(Th3) < V(Th4)), which correspond to quantum transport of the nanoribbon not oxidized, high-oxy, med-oxy and low-oxy, respectively, so creating two nanoconstrictions as well as two regions of quantum confinement. PMID- 27398462 TI - A Facile Chemical Reduction of Graphene-Oxide Using p-Toluene Sulfonic Acid and Fabrication of Reduced Graphene-Oxide Film. AB - We report a cost effective and easy chemical reduction method for exfoliated individual graphene oxide (GO) and GO paper using p-toluene sulfonic acid (PTSA) under mild conditions. Raman spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray photon spectroscopy (XPS), thermo gravimetric analysis (TGA) and transmission electron microscopy (TEM) analysis were performed to investigate the quality of GO reduction. Data resulting from the spectral analysis suggest that the reduction method using PTSA is an efficient method to remove oxygen functionalities in the GO and also as an alternative to commonly used reducing agents. We also fabricated chemically reduced GO (RGO) film from GO film using this method. The RGO film exhibits an electrical conductivity of about 10587 Sm-1. These results suggest that this method is very useful for the reduction of GO and GO film or paper using PTSA in a solution process for flexible electronics due to its facile, efficient and cost effective features. PMID- 27398463 TI - Electrochemical Sensing of Monohydric Alcohols on Different Linkers Imbedded in Between Graphene and Platinum Nanoparticles. AB - We investigated the relationship between the linker's length and the electrooxidation of methanol and ethanol with PtNPs-decorated graphene oxide (GO). The covalently functionalized materials were prepared with three different lengths of the alkane chain as the linker molecules in between GO and platinum nanoparticles (PtNPs). Electrochemically reduced GO-S-(CH2)n-S-Pt [ERGO-S-(CH2)n- S-Pt, wherein n = 2, 3 and 4] was obtained via electrochemical reduction of GO-S (CH2)1-S-Pt in PBS at pH 5. ERGO-S-(CH2)n-S-Pt was characterized by XPS and FE SEM. The XPS result reveals that the Pt at% increased with the increasing of chain length and the surface morphology indicates the surface area increased with the increasing of linker's length. The electrochemical behavior of these modified glassy carbon electrodes (GCEs) were investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and chronoamperometry (CA). The ERGO S-(CH2)n-S-Pt was employed to detect methanol and ethanol; and the ERGO-S-(CH2)4 S-Pt showed a better performance towards alcohol oxidation reaction (AOR) among all ERGO-S-(CH2)n- S-Pt. The detection limit of methanol and ethanol was 1.8 x 10 2 mM and 1.28 x 10-2 mM, respectively, at ERGO-S-(CH2)4-S-Pt. PMID- 27398464 TI - Studies on the Synthesis and Physico-Chemical Properties of Porous LiFe0.9M0.1P2O7 (M = Fe, Co, Mn, Ni) Nanoparticles. AB - The nano-porous LiFe0.9M0.1P2O7 (M = Fe, Co, Mn, Ni) particles were successfully prepared by simple microwave assisted combustion method and studied its detailed physico-chemical properties. The phase purity, crystallinity, functional group identification was revealed through X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. The presence of nanoporous was identified through transmission electron microscopic (TEM) images. The electrical conductivity results illustrated that LiFe0.9Ni0.1P2O7 has higher conductivity (2.85 x 10-7 S cm-1) among the studied systems owing to their negligible grain boundary effect. The normal dielectric behaviour was observed for all the LiFe0.9M0.1P2O7 (M = Fe, Co, Mn, Ni) materials. The paramagnetic behaviour and the Fe3+ state of LiFe0.9M0.1P2O7 were obtained from VSM and Mossbauer spectral analysis respectively. The cyclic voltammogram suggested that the good electrochemical lithium intercalation/de intercalation behaviour of LiFe0.9M0.1P2O7 (M = Fe, Co, Mn, Ni) electrodes in aqueous electrolytes. The obtained diffusion coefficient value is comparable with carbon based materials. PMID- 27398465 TI - Aloe vera Plant Extracted Green Synthesis, Structural and Opto-Magnetic Characterizations of Spinel Co(x)Zn1-xAl2O4Nano-Catalysts. AB - Spinel Co(x)Zn1-xAl2O4 (0 <= x <= 1) nano-catalysts were synthesized by a simple Aloe vera plant extracted green synthesis route. Powder XRD patterns and Rietveld analysis confirmed the formation of single phase, cubic spinel gahnite structure without other impurities. The lattice parameter increased from 8.089 to 8.125 A with increasing CO2+ content. The average crystallite sizes were estimated using Scherrer's method, and it was found to be in the range of 15.72 nm to 26.53 nm. FT-IR spectra showed vibrational stretching frequencies corresponding to the spinel structure. HR-SEM and HR-TEM images showed the features of well particle shaped crystals with nano-sized grains. The elemental compositions of Co, Zn, Al and O were quantitatively obtained from EDX analysis. The band gap energy estimated using Kubelka-Munk method by UV-Visible DRS method, and the values are decreased with increasing the Co2+ content (4.12 eV to 3.67 eV), due to the formation of sub bands in between the energy gap. PL spectra showed emission bands in UV as well as in the visible regions for ZnAl2O4 and Co-doped ZnAl2O4, due to the defect centers acting as the trap levels. VSM measurements revealed that pure ZnAl2O4 has diamagnetic, while Co doped ZnAl2O4 samples (x = 0.2 to 0.8) have superparamagnetism, whereas the sample CoAl2O4 has ferromagnetic in nature. Catalytic oxidation of benzyl alcohol to benzaldehyde was found that the sample Co0.6Zn0.4Al2O4 showed 93.25% conversion with 99.56% selectivity, whereas for pure ZnAl2O4, the conversion was only 86.31% with 92.85% selectivity. PMID- 27398466 TI - Conducting Polymer Nanostructures and Nanocomposites with Carbon Nanotubes: Hierarchical Assembly by Molecular Electrochemistry, Growth Aspects and Property Characterization. AB - Conducting (or pi-conjugated) polymers are promising materials for preparing supramolecular nano-structures and nanocomposites. We report controlled nanostructure syntheses of polypyrrole (PPy) and poylaniline (PANi) via electropolymerization (i.e., in-situ electrochemical anodic oxidation). The density, shape, caliber and thickness of self-assembled PPy micro-containers are regulated by electrochemical potential window for H2 bubbles and number of cyclic voltammetric (potentiodynamic) scans. Likewise, we employed amperometry, chronopotentiometry and potentiodynamic modes using hydrochloric acid as oxidizing agent to prepare PANi nanoparticles and nanotubules. We present our findings from the viewpoint of molecular electrochemistry with growth kinetic aspects yielding mechanistic details (initially forming dimers and oligomers as nucleating agents followed by polymer growth). Also targeted is forming nanocomposites with functionalized single- and multi-walled carbon nanotubes (FSWCNTs and FMWCNTs) as reinforced agent to optimize structural and functional properties. All of these novel nanomaterials are characterized using a range of complementary techniques to establish microscopic structure-property-function relationship. PMID- 27398467 TI - Nanoporous TiO2/SnO2/Poly(3,4-ethylene-dioxythiophene): Polystyrenesulfonate Composites as Efficient Counter Electrode for Dye-Sensitized Solar Cells. AB - A nanoporous composite film combined of conducting inorganic template (TiO2/SnO2) and conducting polymer catalyst (poly(3,4 ethylenedioxythiophene):polystyrenesulfonate, PEDOT: PSS) was developed as an alternative counter electrode for dye-sensitized solar cell (DSSC) through low temperature process. The TiO2/SnO2 template was first fabricated by coating a homogeneous TiO2 nanoparticles blended paste containing a SnCl4 aqueous solution on the conductive substrate, followed by annealing at 150 degrees C. The counter electrode was then completed by spin-coating the PEDOT: PSS aqueous solution into the template and drying at 80 degrees C. The obtained TiO2/SnO2/ PEDOT: PSS (TSP) composite film exhibits more excellent catalytic activity for the tri iodide reduction than the pristine PEDOT: PSS film, resulting in the significant improvements in the fill factor and efficiency of the cells. The values of the fill factor and efficiency respectively increase from 0.564 and 4.79% to 0.699 and 6.54%. Noted that the photovoltaic performances of the TSP based DSSC is very similar to those of the Pt based one. The fill factor and efficiency of the later are 0.696 and 6.48%, respectively. The outstanding properties of the TSP composite film used as the counter electrode can be ascribed to its prominent synergistic effects. In the TSP composite film, the conducting TiO2 is applied as the main skeleton material with the in-situ formed SnO2 as a binder to construct a nanoporous structure for the PEDOT: PSS coating and also to provide numerous high-speed conductive paths for the electron transportation from the substrate to the PEDOT: PSS coating, and the PEDOT: PSS adhered on the TiO2/SnO2 skeleton mainly acts as the catalyst to enlarge its surface area allowing for more active sites for the tri-iodide reduction. PMID- 27398468 TI - Optical and Electrical Investigation of ZnO Nano-Wire Array to Micro-Flower from Hierarchical Nano-Rose Structures. AB - We have demonstrated a simple solvo-chemical and solvo-thermal route to design various nano-structures growth of zinc oxide (ZnO). The shapes and morphologies can be easily controlled by using different ambient conditions. We successfully fabricated ZnO nano-wires array on ITO substrate. Those nano-wire array center gradually formed micro-flower like structure evolved in this solvo-chemical route. This novel synthesis happened under cationic surfactant CTAB in the solution helps to form hierarchical structures of ZnO. The length of nano-wire is around 2.0 um, which formed micro-flower diameter 5.0 um. Micro-flowers were scratched out from ITO substrate thin film and annealed at 650 degrees C in electric oven for 1 hour, eventually this micro-flower transformed to novel nano rose structure confirmed by electron microscopic study. Synthesized nano-rose diameter was around 730 nm. Moreover, we found a drastic change of dielectric behavior and DC conductivity of ZnO nanostructures depending on geometry regulated by the duration of preparation. Interestingly enough, optical and electrical properties also changed due to different crystalline structure formation. The dielectric constant is higher at 7.5 also high threshold voltages at 4 V, corresponds to nano-wires array with micro-flower system. A detail dielectric analysis of one step behavior of broad single relaxation peak was obtained only shows the normal dispersion in this system from 1000 kHz to 10 MHz. While less dielectric constant 1.7 and low threshold voltage 1 V, investigated nano-wires with micro-flower, then nano-rose transition appeared in two step behaviors of double relaxations phenomenon appeared one at low frequency and other at higher frequency region. Besides, I~V response characteristics is new idea about different breakdown voltages and bi-stable DC switching capability. Our work demonstrates the possibility of a fast novel synthesis route using a Solvo-chemical process for this type of nanomaterials transition. This special structural character was able to tune band gap which has potential applications in semiconductor electronic devices. PMID- 27398469 TI - Structural and Magnetic Properties of Dilute Ca2+ Doped Iron Oxide Nanoparticles. AB - Undoped and calcium substituted hematite (alpha-Fe2O3) nanoparticles are synthesized by surfactant-directed co-precipitation and post annealing method. The annealed nanoparticles were found to be in single phase in nature and crystallize in the rhombohedral structure with space group R3c as confirmed by Rietveld refinement of the X-ray diffraction (XRD) data. Average crystallite sizes are calculated to be 20 to 30 nm and 50 to 60 nm for the nanoparticles annealed at 400 and 600 degrees C respectively. Mossbauer spectra for all the nanoparticles could be fitted with a sextet corresponding to the single magnetic state of the iron atoms in its Fe3+ state in the hematite matrix. The FTIR and Raman spectra of all the samples correspond to specific modes of alpha-Fe2O3. UV Vis spectra of annealed samples showed broad peaks in the range of 525-630 nm resulting from spin-forbidden ligand field transition together with the spin-flip transition among the 2t2g states. The estimated band gap energies were in the range of 1.6 to 1.9 eV which are much lower than the reported values for nano hematite. From the room temperature magnetic hysteresis loop measurements, weak ferromagnetic behavior is observed in all undoped and Ca2+ doped hematite samples. Morin temperature (T(M)) is calculated to be 257 and 237 K for 1.45% doped samples with particle size 54 and 27 nm respectively. The sample with Ca content of 1.45 wt% when annealed at 400 degrees C showed that the particles were of different shapes which included both quasi spherical and rod shaped. On annealing the same sample at 600 degrees C, the nanorods collapsed to form bigger spherical and ellipsoidal particles. PMID- 27398470 TI - Effect of Temperature, Solvent and Precursor Concentration on Anti-Aggregation of ZnO Nanoparticles Prepared by Polyol Method. AB - We have investigated the formation mechanism of ZnO microspheres in polyol medium. The synthesis conditions have been varied with respect to temperature, medium and Zn-precursor concentration. The X-ray diffraction (XRD) and Raman spectroscopy result shows that the prepared ZnO nanoparticles are hexagonal wurtzite crystal structure and quite crystalline in nature. High resolution transmission electron microscopy (HRTEM) image indicates that the microsphere consists of aggregated nanoparticles in the range of 6 nm to 15 nm. The samples prepared in ethylene glycol medium shows a characteristic ether bond vibration mode in FTIR and it is additionally confirmed by NMR analysis. Initially, the nanoparticles are self-assembled into loosely packed microsphere and then the particles are densely packed by ether bonds formed between the glycol molecules adsorbed on adjacent particles which then grow as perfect microspheres. The sample prepared in EG medium at 150 degrees C did not show much aggregation. This study proposes the possible mechanism for the formation of ZnO microsphere. PMID- 27398471 TI - Surface Grafted Hyper-Branched Polyglycerol Stabilized Ag and AuNPs Heterogeneous Catalysts for Efficient Reduction of Congo Red. AB - Six types of insoluble polymer-supported beads immobilized with Ag and AuNPs nanoparticle catalysts were synthesized using newly prepared three different types of polymer-supported poly(styrene)-co-poly(vinyl benzene chloride) matrix (PS-PVBC), surface grafted with (i) triethanolamine (TEA), (ii) glycidyl trimethyl ammonium chloride (GTMAC) and (iii) hyper-branched polyglycerol (HPG) and Ag and AuNPs as a catalytic moiety and thus yield polymer-supported nanoparticle catalysts viz., PS-PVBC-TEA-AgNPs and AuNPs, PS-PVBC-g-GTMAC-AgNPs and AuNPs and PS-PVBC-g-GTMAC-AgNPs and AuNPs catalyst respectively. These bead shaped heterogonous nanoparticle catalysts were characterized by UV-Vis, FTIR, FESEM, HRTEM and TGA techniques. The efficiency for stabilization/loading of metal nanoparticles with respect to varied intensities of hyper-branched chain grafted onto their matrix was screened by determining their comparative catalytic activity. The catalytic potential of these catalysts was inspected through reduction of Congo Red (CR) keeping pseudo first order identical reaction condition. The observed k(obs) values reveal that irrespective of metal the catalyst derived from hyper-branched polyglycerol as stabilizing agent viz., PS PVBC-g-HPG-AgNPs and PS-PVBC-g-HPG-AuNPs shows (k(obs) = 3.98 x 10-2 min-1 and k(obs) = 4.54 x 10-2 min-1) four and two times greater activity than the catalyst derived from TEA and GTMAC hyper-branched chain. Further, for the same reaction PS-PVBC-g-HPG-AuNPs showed more efficiency than the PS-PVBC-g-HPG AgNPs catalyst. The stability and reusability of the superior catalyst viz., PS-PVBC-g-HPG-AuNPs catalyst was observed to be good even at the sixth cycle. This catalyst can be continuously used to conduct the reduction of various dyes in continuous mode operation in industrial scale. PMID- 27398472 TI - Zinc Oxide-Multi Walled Carbon Nanotubes Nanocomposites for Carbon Monoxide Gas Sensor Application. AB - Zinc oxide (ZnO)/multi walled carbon nanotubes (MWCNTs) composites based sensors with different ZnO concentrations were fabricated to improve carbon monoxide (CO) gas sensing properties in comparison to the sensors based on bare MWCNTs. To study the structure, morphology and elemental composition of the resultant products, X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM) and Energy dispersive X-ray spectroscopy (EDS) were carried out. It has been observed that as the concentration of ZnO is increased more and more ZnO nanoparticles in the form of nodes get attached to MWCNTs resulting the reduction in average diameter of MWCNTs. The typical response of ZnO/MWCNTs composites based gas sensors for different CO concentrations (40, 100, 140 and 200 ppm) was studied by using very advanced sensing setup attached to I-V measurement system. Different sensing parameters such as: resistive response, sensitivity and response time were estimated at room temperature for all the fabricated sensors. The results indicated that the sensor based on nanocomposite which has 30 mg ZnO dispersed on 20 mg MWCNTs showing highest sensitivity and fastest response. All the sensors showed response times ranging from 8 to 23 seconds. The sensing mechanism behind the sensors based on ZnO/MWCNTs nanocomposites for CO gas at room temperature is also discussed in the present report. PMID- 27398473 TI - Sesamum indicum Plant Extracted Microwave Combustion Synthesis and Opto-Magnetic Properties of Spinel MnxCo1-xAl2O4Nano-Catalysts. AB - Spine Mn(x)Co1-xAl2O4 (x = 0, 0.3 and 0.5) nanoparticles were synthesized using Sesamum indicum (S. indicum) plant extracted microwave-assisted combustion method. S. indicum plant extract simplifies the process, provides an alternative process for a simple, economical and environment friendly synthesis. The absence of surfactant/catalysts has led to a simple, cheap and fast method of synthesis of spinel nanoparticles. The as-synthesized spinel nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, high resolution scanning electron microscopy (HR-SEM), high resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray analysis (EDX), Brunauer Emmett Teller (BET) surface area analysis, UV-Visible diffuse reflectance spectroscopy (DRS), Photoluminescence (PL) spectroscopy, and vibrating sample magnetometer. The formation of spinel nanoparticles was confirmed by HR-SEM and HR-TEM and their possible formation mechanisms were also proposed. Powder XRD, FT-IR, SAED and EDX results confirmed the formation of pure and single cubic phase CoAl2O4 with well-defined crystalline. The optical property was determined by DRS and PL spectra. VSM measurements revealed that pure and Mn-doped CoAl2O4 samples have weak ferromagnetic behavior and the magnetization values increases with increasing the concentration of Mn2+ ions in the CoAl2O4 lattice. The sample Mn0.5Co0.5Al2O4 possessed higher surface area and smaller crystallite size than other samples, which led to enhance the performance toward the selective oxidation of benzyl alcohol into benzaldehyde. PMID- 27398474 TI - Optical Absorption Cross Section of Individual Multi-Walled Carbon Nanotubes in the Visible Region. AB - The aim of the present work is to determine the optical absorption cross section for visible radiation of various types of multiwall carbon nanotubes (MWCNTs) having different dimensions through macroscopic optical measurements. This is achieved by dispersing MWCNTs in polydimethylsiloxane (PDMS) and preparing composite films. Different percentages (0.0% to 1.5%) of each MWCNTs type were mixed into the PDMS matrix using high speed mechanical stirring (~1000 rpm) and ultrasonication (~37 kHz) to reach optimal dispersion. By using doctor blading technique, 100 um thick uniform films were produced on glass. They were then thermally cured and detached from the glass to get flexible and self-standing films. Field-Emission Scanning Electron Microscope (FESEM) analysis of cryo fractured composite samples was used to check the dispersion of MWCNTs in PDMS, while Raman spectroscopy and FTIR were employed to rule out possible structural changes of the polymer in the composite that would have altered its optical properties. Total and specular reflection and transmission spectra were measured for all films. The absorption coefficient, which represents the fractional absorption per unit length and is proportional to the concentration of absorbing sites (i.e., MWCNTs at photon energies upon which PDMS is non-absorbing), was extracted. For each MWCNTs type, the absorption cross section of an individual MWCNT was obtained from the slope of absorption coefficient versus MWCNTs number density curve. It was found to be related with MWCNT volume. This method can be applied to all other nanoparticles as far as they can be dispersed in a host transparent matrix. PMID- 27398475 TI - The Preparation and Electrochemical Performance of Olivine Cathode Materials Based on LiMn1/3Fe1/3Co1/3PO4/C. AB - Solid solution LiMn1/3Fe3Co1/33PO4/C ternary materials were prepared by sol-gel method with glycine or citric acid as chelating agents. SEM images indicate that the particles are well distributed with regular morphologies, and the particle sizes are around 300 nm for both samples. The cyclic voltammetry (CV) and charge discharge curves show that the reversibility of Mn2+/Mn3+ couple is improved apparently. The redox potential corresponding to Fe2+/Fe3+ couple has been increased which is beneficial to the energy density, and the redox potential related to Co2+/Co3+ couple has been declined which could accelerate dynamics of intercalation/deintercalation and make the electrochemical reaction more smoothly. The obtained LiMn1/3Fe1/3Co1/33PO4/C materials with glycine as chelating agent deliver a capacity of 151.5, 142.6, 122.8, 97.9 mAh g-1 at 0.05 degrees C, 0.1 C, 0.5 C and 1 C, respectively. And the obtained material with citric acid as chelating agent delivers a capacity of 150.8, 135.0, 111.5, 85.2 mAh g-1, respectively, at the same rates. PMID- 27398476 TI - Synthesis and Visible Photodegradation Enhancement of CdS/mpg-C3N4 Photocatalyst. AB - A series of visible-light-induced CdS/mpg-C3N4 nanocomposites were fabricated vis the solvothermal method and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), diffuse reflectance spectroscopy (DRS) and photoluminescence (PL) spectroscopy analysis. The results show that CdS nanoparticles are homogenously dispersed on the sheet of mesoporous g-C3N4. The CdS/mpg-C3N4 nanocomposites show much higher visible-light-driven photocatalytic activity than individual mpg-C3N4 and CdS for methylene blue (MB) and phenol degradation. The optimal CdS content with the highest photocatalytic activity is determined to be 40%, which is almost 6.4 and 1.6 times higher than that those of individual mpg-C3N4 and CdS for the degradation of MB, and 12.2 and 2.2 folds for the degradation of phenol. The enhancement in photocatalytic activity and stability should be assigned to the effective separation and transfer of photogenerated charges coming from the well matched overlapping band-structure between mpg-C3N4 and CdS. Radical trap experiments show that both the holes and O.-2 are main oxidative species of CdS/mpg-C3N4 for MB degradation under visible light irradiation. Finally, the possible mechanism for the enhancement of the visible light performance is proposed. PMID- 27398477 TI - Facile One-Pot Polyol Method for the Synthesis of Uniform Size Silver Nanowires. AB - This study reports the development of a facile and efficient one-pot polyol method for the synthesis of silver nanowires. The seed and growth of silver nanowires under different reaction conditions were characterized and measured. The pertinent variables such as temperature, time, concentration and capping agent were investigated. Moreover, the effect of seeding at two different stages initial stage and secondary stage-was studied and discussed on the size control of silver nanowires. In particular, silver nanowires with diameter less than 40 nm and length over 25 um in a narrow distribution, was obtained through a novel method in which reaction flask was placed in a low-temperature bath after seeding for some time in the high-temperature bath. This approach may be useful for the fabrication of uniform, large aspect ratio silver nanowires for optoelectronic applications. PMID- 27398478 TI - Substrate Temperature Effects on Room Temperature Sensing Properties of Nanostructured ZnO Thin Films. AB - Zinc oxide (ZnO) thin films were deposited on glass substrates using chemical spray pyrolysis technique at different substrate temperatures such as 523, 623 and 723 K. X-ray diffraction (XRD) patterns confirmed the formation of polycrystalline films with hexagonal wurtzite crystal structure and revealed the change in preferential orientation of the crystal planes. Scanning electron micrographs showed the formation of uniformly distributed spherical shaped grains at low deposition temperature and pebbles like structure at the higher temperature. Transmittance of 85% was observed for the film deposited at 723 K. The band gap of the films was found to be increased from 3.15 to 3.23 eV with a rise in deposition temperature. The electrical conductivity of the films was found to be improved with an increase in substrate temperature. Surface of ZnO thin films deposited at 523 K, 623 K and 723 K were found to be hydrophobic with the contact angles of 92 degrees , 105 degrees and 128 degrees respectively. The room temperature gas sensing characteristics of all the films were studied and found that the film deposited at 623 K showed a better response towards ammonia vapour. PMID- 27398479 TI - Acetones Removal with Fe Doped Titanium Nano Tube Catalysts Prepared from Slag Iron in Steel Plant. AB - TiO2 has been studied most commonly because it has high stability, non-toxicity, high catalytic activity, and highly conductivity. Many studies have shown that TiO2 would generate electron-hole pairs illuminated with UV and surround more energy than that before being illuminated. However, the surface area of TiO2 is not large enough and the adsorption capacity is small. In this study, the titanium nano tube (TNT) catalysts were prepared to increase the surface area and adsorption capacity. The Fe-TNT was also prepared from slag iron since many slag iron cause waste treatment problems. In this study, the effect of Fe loading, including 0.77%, 1.13%, 2.24% and 4.50%, on acetone removal was also assessed since TNT doped with transitional or precious metals can be used to improve catalytic reaction efficiency. Furthermore, four kinds of VOCs concentration, including 250, 500, 1000 and 1500 ppm were tested. Four kinds of retention time, including 0.4, 0.8, 4.0 and 6.0 sec, and four kinds of dosage, including 0.15, 0.25, 0.30 and 0.45 g cm-3, were also assessed. In this study, the adsorption capacity of Fe-TNT was 18.8, 23.3, 28.9 and 32.6 mg g-1 for acetone of 250, 500, 1000 and 1500 ppm, respectively. Four kinds of temperature, including 150, 200, 250 and 300 degrees C were tested in catalytic reaction system. The results showed removal efficiency increased with increasing temperature. The efficiency can be reached 95% under the conditions with the dosage higher than 0.3 g cm-3, temperature higher than 270 degrees C and retention time higher than 270 degrees C. Reaction efficiency was 20, 31, 41 and 96% at the temperature of 150, 200, 250 and 300 degrees C, respectively. PMID- 27398480 TI - Microstructure, Optical and Photocatalytic Properties of TiO2 Thin Films Prepared by Chelating-Agent Assisted Sol-Gel Method. AB - Single and multilayer TiO2 thin films coated on two types of soda-lime glass substrates (microscope slides and cylinders) were prepared by a chelating agent assisted sol-gel method, using ethyl acetoacetate as a chelating agent, dip coating and calcination at 500 degrees C for 2 h in air. Phase composition, microstructural, morphological and optical properties of thin films were comprehensively investigated by using XRF, advanced XRD analysis, Raman and UV vis spectroscopy and AFM. It was found out that the thickness of thin films increases linearly with increasing number of deposited layers, indicating a good adhesion of the titania solution to a glass substrate as well as to a previously calcined layer. 1 layer film crystallized to anatase-TiO2(B) mixture with minor/negligible amount of nanosized brookite, 2-4 layers films crystallized to anatase-brookite-TiO2(B) mixture. In contrast to other multilayers films, 4 layers film was highly inhomogeneous. The different phase composition of thin films was clarified based on the crystallization via titanate/s and metastable monoclinic TiO2(B) as a consequence of several phenomena; the diffusion of Na+ ions from a soda-lime glass substrate, acidic conditions and repeated thermal treatment. The multilayer films were in average highly transparent (80-95%) in the visible light region with the sharp absorption edge in the UV light region. Additionally, the photocatalytic properties of selected multilayer films were compared in AO7 photodegradation. Photocatalytic experiments showed that thicker 4 layers film of tricrystalline anatase-brookite-TiO2(B) phase mixture was similarly active as thinner 3 layers film of similar phase composition, which may be a consequence of the inhomogeneity of the thicker film. PMID- 27398481 TI - Use of Spectroscopic Techniques to Reveal the Nature of the Interactions of Two Sialic Acid Specific Lectins with Gold Nanoparticles. AB - From UV-vis absorption, steady state and time resolved fluorescence measurements coupled with circular dichroism (CD) spectral studies, it was revealed that among the two lectins: Sambucus nigra agglutinin (SNA) and Saraca indica (saracin II), SNA forms stronger binding complex in the ground state with gold nanoparticles (GNPs). From the measurements of Stern-Volmer (SV) constants Ksv, and binding constants K(A) and number of binding sites two important inferences could be drawn. Firstly, the fluorescence quenching is primarily due to static quenching and secondly SNA forms stronger binding with GNPs relative to the other lectin saracin II. Synchronous fluorescence spectral measurements further substantiate this proposition of exhibiting the fully exposed tryptophan residue in case of SNA. It appears that the lectin SNA adopted a relatively looser conformation with the extended polypeptide structures leading to the exposure of the hydrophobic cavities which favoured stronger binding with GNPs. CD measurements demonstrate that gold nanoparticles when interact with the lectins (glycoproteins), no significant distortion in the structural pattern of the later occurs. The unaltered identity in the secondary structural pattern of both SNA and saracin II in presence of gold nanoparticles hints that GNPs may be used as useful drug or drug delivery systems. PMID- 27398482 TI - Near and Mid-Infrared Emission Characteristics of Er3+/Tm3+/Ho3+-Doped LiYF4 Single Crystals Excited by Laser Diode. AB - Yttrium lithium fluoride (LiYF4) single crystals triply doped with Er3+/Tm3+/Ho3+ are synthesized by a vertical Bridgman method. Absorption spectra, emission spectra, and decay curves are measured to investigate the luminescent properties of the crystals. Compared with Er3+ singly doped and Er3+/Tm3+ and Er3+/Ho3+ doubly doped LiYF4 crystals, an intense emission around 2.7 um can be obtained in the triply doped LiYF4 crystal under excitation of 980 nm laser diode. Meanwhile, the near infrared emission at 1.5 um from Er3+ in the triply doped crystal is effectively reduced. The possible energy transfer processes and the luminescent mechanisms for enhancing emission at 2.7 um and quenching emission at 1.5 um in the Er3+/Ho3+/Tm3+ triply doped crystals are proposed. The large energy transfer efficiency of 82.0% and excellent optical transmission indicate that this Er3+/Tm3+/Ho3+ triply doped crystal can be considered as a promising material for a mid- infrared laser at 2.7 um. PMID- 27398483 TI - Growth and Optical Spectra of Tb3+/Sm3+/Ce3+ Triply Doped LiYF4Single Crystals for White-Light LEDs. AB - The Tb3+/Sm3+/Ce3+ triply doped LiYF4 single crystals were grown by a modified Bridgman method. The absorption spectra, excitation spectra, and fluorescence spectra of Tb3+/Sm3+/Ce3+ ions in LiYF4 crystals were measured. The fluorescence spectra of several bands, mainly located at purplish blue ~413 nm (5D3 --> 7F5), yellowish green ~542 nm (5D4 --> 7F5), and red ~643 nm (4G5/2 --> 6H9/2), were observed under excitation of ultraviolet light. White light could be generated by the mixture of the multicolor lights. The luminous intensities varied slightly with the excitation wavelength from 300 nm to 400 nm and doping Tb3+/Sm3+/Ce3+ ion concentration. The chromatic- ity coordinates of the crystal could be modified by changing the excitation wavelengths and the concentrations of Tb3+/Sm3+/Ce3+ ions. A near-ideal white light emission could be obtained from 1.25 mol% Tb3+, 1.98 mol% Sm3+, 0.44 mol% Ce3+ triply doped LiYF4 single crystal with chro- maticity coordinates of x = 0.3090, y = 0.3223, color temperature Tc = 6777 K, color rendering index Ra = 77 and color quality scale Qa = 76 under the excitation of a 374 nm light. PMID- 27398484 TI - Energy Transfer and 1.8 um Emission in Tm3+/Yb3+ Co-Doped LiYF4Crystal. AB - LiYF4 single crystals co-doped with various Tm3+/Yb3+ concentrations were grown using the Bridg- man method. The luminescent properties of the crystals were investigated through emission spectra, emission cross section, and decay curves under excitation by 980 nm. Compared with the Tm3+ single-doped LiYF4 crystal, an enhanced emission band from 1600 to 2150 nm was observed upon excitation of a 980 nm laser diode. The energy transfer from Yb3+ to Tm3+ and the optimum fluo- rescence emission around 1.80 um of Tm3+ ion were investigated. The maximum emission cross section at 1.8 um was calculated to be 1.48 x 10-20 cm2 according to the measured absorption spectrum. The high energy transfer efficiency of 86.5% from Yb3+ to Tm3+ ion demonstrate that the Yb3+ ions can efficiently sensitize the Tm3+ ions. PMID- 27398486 TI - Visual Screening and Colorimetric Determination of Clenbuterol and Ractopamine Using Unmodified Gold Nanoparticles as Probe. AB - In this paper, a sensitive method for the colorimetric detection of clenbuterol and ractopamine using citrate-stabilized gold nanoparticles (AuNPs) as probe was developed. The concentration of clenbuterol and ractopamine could be determined with naked eyes or a UV-vis spectrometer. By optimizing the influence of NaHSO4 and incubation time, clenbuterol could be detected in the linear range of 0.1-4 ug/mL with the detection limit of 0.0158 ug/mL, and ractopamine could be detected in the linear range of 1-9 ug/mL with the detection limit of 0.0229 ug/mL. The proposed method could be successfully applied to detect clenbuterol and ractopamine in pig urines by a simple pre-treatment with excellent recoveries. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for the analysis of clenbuterol and ractopamine. PMID- 27398485 TI - Hydrothermal Synthesis and Luminescence Properties of Eu2+- and Eu3+-Doped SrAIF5 Nanorods. AB - Eu2+- and Eu3+-doped SrAIF5 nanorods were synthesized via a hydrothermal process. The crystal structure and morphology of the final products were characterized by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). The prepared nanorods' diameters range from 40 to 50 nm, and lengths range from 400 nm to 2 um along with the doped concentration of rare earth. The f-f transitions of Eu2+ can be observed in the SrAlF5:Eu2+ nanorods at room temperature, and the photo-luminescent (PL) properties of SrAlF5:Eu3+ nanorods are also described. PMID- 27398487 TI - Recyclable Photo-Thermal Nano-Aggregates of Magnetic Nanoparticle Conjugated Gold Nanorods for Effective Pathogenic Bacteria Lysis. AB - We describe the nucleophilic hybridization technique for fabricating magnetic nanoparticle (MNP) around gold nanorod (AuNR) for desired photo-thermal lysis on pathogenic bacteria. From the electromagnetic energy conversion into heat to the surrounding medium, a significant and quicker temperature rise was noted after light absorption on nanohybrids, at a controlled laser light output and optimum nanoparticle concentration. We observed a similar photo-thermal pattern for more than three times for the same material up on repeated magnetic separation. Regardless of the cell wall nature, superior pathogenic cell lysis has been observed for the bacteria suspensions of individual and mixed samples of Salmonella typhi (S.typhi) and Bacillus subtilis (B.subtilis) by the photo-heated nanoparticles. The synthesis of short gold nanorod, conjugation with magnetic nanoparticle and its subsequent laser exposure provides a rapid and reiterated photo-thermal effect with enhanced magnetic separation for efficient bactericidal application in water samples. Resultant novel properties of the nano-aggregates makes them a candidate to be used for a rapid, effective, and re-iterated photo thermal agent against a wide variety of pathogens to attain microbe free water. PMID- 27398488 TI - Discrete Dipole Approximation Simulation of Nearly Touching Plasmonic Au Dimers and Influence of Particle Shape Assembly on Optical Response. AB - The method Discrete Dipole Approximation (DDA) is used to calculate the extinction spectra and field distribution of three types of dimers. In the paper we provide a systematic analysis of the optical response of different nanoscopic dimer structures with relatively small gap distances. A description is given about how the energy and excitation cross sections of dimer plasmons depend on nanoparticle separation. Resonance peaks of dimers show red-shift compared with single nanoparticle. Dimers formed by different single particle display distinct optical response. Interaction junctions in dimers can serve as hot spots for field enhancement. Field distribution in gaps made of two flat planes is nearly continuous. Changing gaps between two particles in dimers can tune the resonance wavelength effectively as well as different particle ensembles. Existence of sharp corners can attract and change field distribution. It is not effective volume but the effective cross-section that dominates the extinction efficiency. PMID- 27398489 TI - Fabrication of Ag-Decorated CaTiO3 Nanoparticles and Their Enhanced Photocatalytic Activity for Dye Degradation. AB - CaTiO3nanoparticles of 30-40 nm in size were synthesized via a polyacrylamide gel route. Ag nanoparticles with size of 8-16 nm were deposited onto CaTiO3particles by a photochemical reduction method to yield CaTiO3@Ag composites. The photocatalytic activity of prepared samples was evaluated by degrading methyl orange under ultraviolet irradiation. It is demonstrated that Ag-decorated CaTiO3 particles exhibit an enhanced photocatalytic activity compared to bare CaTiO3 particles. After 60 min of photocatalysis, the degradation percentage of MO increases from 54% for bare CaTiO3particles to 72% for CaTiO3@Ag composites. This can be explained by the fact that photogenerated electrons are captured by Ag nanoparticles and photogenerated holes are therefore increasingly available to react with OH-/H2O to generate hydroxyl (.OH) radicals. .OH radicals were detected by fluorimetry using terephthalic acid as a probe molecule, revealing an enhanced yield on the irradiated CaTiO3@Ag composites. In addition, it is found that the addition of ethanol, which acts as an .OH scavenger, leads to a quenching of .OH radicals and simultaneous decrease in the photocatalytic efficiency. This suggests that .OH radicals are the dominant active species responsible for the dye degradation. PMID- 27398490 TI - Grafting Poly(ethylene glycol) Onto Single-Walled Carbon Nanotubes by Living Anionic Ring-Opening Polymerization. AB - Recent years, many methods have been developed to widen the practical application of single-walled carbon nanotubes (SWCNTs). Among them, PEGylation is a general strategy to endow functionality, biocompatibility as well as its good solubility. In this paper, poly(ethylene glycol) (PEG) is successfully grafted onto SWCNTs through living anionic ring-opening polymerization of ethylene oxide (EO). By controlling the amount of monomer and initiator, a series of PEGylated SWCNTs with different PEG molecular weight and density are prepared. Then, the as prepared SWCNTs have been verified by thermogravimetric analyses (TGA), Raman spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS). Finally, the protein resistance property of the PEGylated SWCNTs is investigated. It is found that these PEGylated SWCNTs have a good protein resistance property and the higher the content of PEG grafted on the SWCNTs, the less adsorption amount of BSA and the larger capacity to resist protein absorption. This work provides a novel method to prepare PEGylated SWCNTs. PMID- 27398491 TI - The Photovoltaic Performances of PVdF-HFP Electrospun Membranes Employed Quasi Solid-State Dye Sensitized Solar Cells. AB - The PVdF-HFP nanofiber membranes with different molecular weight were prepared by electrospinning technique and were investigated as solid state electrolyte membranes in quasi solid state dye sensitized solar cells (QS-DSSC). The homogeneously distributed and fully interconnected nanofibers were obtained for all of the prepared PVdF-HFP electrospun membranes and the average fiber diameters of fabricated membranes were dependent upon the molecular weight of polymer. The thermal stability of electrospun PVdF-HFP membrane was decreased with a decrement of molecular weight, specifying the high heat transfer area of small diameter nanofibers. The QS-DSSC fabricated with the lower molecular weight PVdF-HFP electrospun nanofiber membrane exhibited the power conversion efficiency of 1 = 5.38%, which is superior over the high molecular weight membranes and is comparable with the liquid electrolyte. Furthermore, the electrospun PVdF-HFP membrane exhibited long-term durability over the liquid electrolyte, owing to the higher adsorption and retention efficiencies of liquid electrolyte in its highly porous and interconnected nanofibers. Thus the proposed electrospun PVdF-HFP membrane effectively tackled the volatilization and leakage of liquid electrolyte and provided good photoconversion efficiency associated with an excellent stability, which constructs the prepared electrospun membranes as credible solid state candidates for the application of QS-DSSCs. PMID- 27398492 TI - Structure and Characteristic of LiFePO4 Cathode Material Synthesized in the Mixed Solvent Environment. AB - In this paper, LiFePO4 samples were synthesized in the water/ethanol mixture solvent environment with different volume ratio of water/ethanol, and the effects of different solvent environment (different water/ethanol ratio) on the morphology, the crystal structure and the cell performances were studied in detail. The prepared samples were investigated comparatively by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and various electrochemical testing techniques. The results showed that the water/ethanol ratio seriously affected the crystal structure, the micro morphologies and the electrochemical properties of the resulting LiFePO4-based electro-active material. And the growth of [010] direction of LiFePO4 crystal was limited with the increase of alcohol proportion in the mixed solvent, while the size of obtained particles became small in the same process. In addition, LiFePO4 samples obtained at high alcohol content presented the improved specific capacity and rate performances. Specially, the LFP-D electrode displayed the discharge capacity of 153.2 mAh . g-1 at the rate of 0.1 C and the improved rate performance of 150.6, 143.6, 133.8, 121.4, 99.5 and 78.2 mAh . g-1 at 0.2 C, 0.5 C, 1 C, 2 C, 5 C and 10 C, respectively. PMID- 27398493 TI - Highly Aligned Poly(vinylidene fluoride-co-hexafluoro propylene) Nanofibers via Electrospinning Technique. AB - We report on the simple way of obtaining aligned poly(vinylidiene fluoride-co hexafluoropropylene) (PVDF-HFP) nanofibers by electrospinning process. The collector drum rotation speed was adjusted to prepare well aligned PVDF-HFP nanofibers. The degree of alignment and the orientation of PVDF-HFP nanofibers can be significantly altered by varying the speed of collector drum rotation. The resultant PVDF-HFP nanofibers were systematically characterized. From the scanning electron microscopy data, it was found that the electrospun PVDF-HFP nanofibers were formed with well-aligned nature. The X-ray diffraction results revealed that the electrospun PVDF-HFP nanofibers with beta-phase can be formed by the increased collector drum rotation speed. Overall, the collector rotation speed during the electrospinning process plays an important role in obtaining well-aligned and improved characteristics of PVDF-HFP nanofibers. PMID- 27398494 TI - Immobilization of Lipase by Adsorption Onto Magnetic Nanoparticles in Organic Solvents. AB - In order to improve the performance of lipase in organic solvents, a simple immobilization method was developed by adsorption of lipase onto Fe3O4@ SiO2magnetic nanoparticles in organic solvent. Among the solvents tested, toluene was found to be the most effective solvent for the immobilization. A maximum immobilization yield of 97% and relative activity of 124% were achieved in toluene at 30 degrees C. The optimal temperature, enzyme loading and water activity were 30 degrees C, 1.25 mg/mg support and 0.48 aw, respectively. The residual activity of immobilized lipase was 67% after 10 cycles of use. The advantages of the immobilized lipase including easy recovery, high stability, and enhanced activity of immobilized lipase in organic solvents show potential industrial applications in anhydrous solvents. PMID- 27398495 TI - The Photoluminescence Properties of Dendritic Phosphors Ca2Gd8(SiO4)6O2:A (A = Eu3+ and Dy3+) for White-Light-Emitting Diodes. AB - Ca2Gd8(SiO4)6O2:A (A = Eu3+ and Dy3+) phosphors were successfully synthesized by the sol-gel process. X-ray diffraction (XRD), thermogravimetric and differential thermal analysis (TG-DTA), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and photoluminescence spectra were used to characterize the resulting phosphors. The results of XRD indicated that the diffraction peaks of the phosphor powder agreed well with the standard card. Under short ultraviolet excitation, the doped rare earth ions (A) showed their characteristic emis- sions in Ca+Gd8(SiO4)6O2 phophors, i.e., 5D0 --> 7F2 (615 nm) for Eu3+ and 4F9/22 --> 6H15/2 (483 nm) and 4F9/2 --> 6H13/2 (575 nm) for Dy3+. The optimum concentration for doped rare earth ions was determined to be 9 mol% Eu3+ and 3 mol% Dy3+ of Gd3+ in Ca2Gd8(SiO4)6O2 PMID- 27398496 TI - Fabrication of Improved Dye-Sensitized Solar Cells with Anatase/Rutile TiO2Nanofibers. AB - Using the method of electrospinning followed by annealing at different temperatures, TiO2 nanofibers with different phases were successfully prepared. Dye sensitized solar cells were fabricated using these TiO2 nanofiber mats as the photoanode. The morphologies and photovoltaic performance of the cells were investigated in detail. By optimizing the annealing temperature and the thickness of the photoanode, a power conversion efficiency of 6.12% and a fill factor of 0.65 were obtained. A treatment with TiCl4was employed to further improve the photoanodes. The resulting DSSC device employing the TiC4-treated anodes exhibited an improved efficiency of 7.06% and a fill factor of 0.73. These performance improvements were attributed to the different crystalline structures of the mesoporous composite anatase/rutile TiO2 nanofibers, which featured stair step energy levels and the high surface area of close grain packing. These positive results suggest that the electrospun nanofiber photoanode provides an effective means of efficient charge transport for application in dye-sensitized solar cells. PMID- 27398497 TI - White Light Emission and Luminescence Dynamics in Eu3+/Dy3+ Codoped ZnO Nanocrystals. AB - In order to expand the use of ZnO in advanced display and lighting device applications, such as distinguishable emissive flat panel displays and liquid crystal display backlights, Eu3+/Dy3+-codoped ZnO nanocrystals were synthesized using a low temperature wet chemical doping technique and chemical surface modification. X-ray diffraction patterns revealed that co-doping Eu3+ and Dy3+ does not change the wurtzite structure of ZnO. A high-resolution TEM image showing obvious lattice fringes confirmed the high crystallinity of the nanosized sample. The luminescence and dynam- ics of Eu3+/Dy3+-codoped ZnO nanocrystals of various doping concentrations were studied under ultraviolet excitation. Excitation into the ZnO conduction band was also studied. ZnO doped with Eu3+ and Dy3+ ions exhibited a strong blue (483 nm) emission from the 4F9/2 --> 6H15/2 transition of Dy3+ ions, a yellowish-green (575 nm) emission from the 4F9/2 --> 6H13/2 transition of Dy3+ ions and a red (612 nm) emission from the 5D0 --> 7F2 transition of Eu3+ ions, without a defect background. Undoped ZnO emitted a broadband green light, demonstrating an efficient energy transfer from the ZnO host to the Eu3+ and Dy3+ ions. Moreover, energy transfer from the Eu3+ ions to the Dy3+ ions in the ZnO host was also observed by analyzing luminescence decay curves. The luminescence dynamics of the Eu3+/Dy3+-codped ZnO sample indicate that as the Eu3+ concentration increased, both the rise and the decay time constants of the 4H9/2 level of the Dy3+ ions became longer, while the decay time constants of the 5D0 level of the Eu3+ ions became shorter, suggesting an energy transfer from the Eu3+ ions to the Dy3+ ions in the ZnO host. Furthermore, by adjusting the doping concentration ratio of Eu3+ and Dy3+ ions, the Eu3+/Dy3+ codoped ZnO phosphors emitted strong white luminescence with a high color purity and high color rendering index. The results indicate that the Eu3+/Dy3+-codoped ZnO phosphors are promising light-conversion materials, and have the potential to be used in field emission display devices and LCD backlights. PMID- 27398498 TI - Tuning Crystal Phase and Emission Properties of Upconversion Nanocrystals Through Lanthanide Doping. AB - Infrared-to-visible upconversion fluorescent nanocrystals of Yb3+/Er3+-codoped NaYF4 and Yb3+/Er3+/Gd3+-tridoped NaYF4 were synthesized using a modified coprecipitation process. X-ray diffraction and transmission electron diffraction scans of the nanocrystals confirmed that Gd3+ doping caused a phase transition to occur in the nanocrystals, changing them from a cubic to a hexagonal phase. Hexagonal phase Yb3+/Er3+/Gd3+-tridoped NaYF4 nanocrystals displayed much stronger and sharper upconversion luminescence, and larger intensity ratios of red over green emissions relative to their cubic phase counterparts. The influence of the crystal phase on the upconversion emission properties was explored by use of excitation power dependence curves, dynamic fluorescence and Raman spectra. The results suggest that the cubic-to-hexagonal phase transition decreases the crystal field symmetry, and then enhances upconversion luminescence intensity by relaxing forbidden selection rules. The conversion into the hexagonal phase also increases the number of phonon modes, and consequently improves the phonon-assisted energy transfer efficiency from Yb3+ to Er3+, thus facilitating the output of red emissions. PMID- 27398499 TI - Defects in AIN/GaN Superlattice: First Principle Calculations. AB - In this paper we investigate the atomic configurations, electronic structure and formation energies of native point defects, (such as vacancies and self interstitials), in an AIN/GaN superlattice (SL) constructed on a wurtzite structure along a [0001] growth direction. Comprehensive first-principle calculations based on the density functional theory (DFT) are used. Cation and anion vacancies in the neutral charge state are calculated. For the native defects, the results showed that the most favorable configurations are the cation vacancies at the interface of the SL, or the anion vacancies in the GaN wells. Considering the formation energies of different vacancies, the results show that the nitrogen vacancy has the lowest formation energy, indicating that they are significantly the most stable configuration, and thus should be expected to be the major defect in a AIN/GaN superlattice. PMID- 27398500 TI - Effect of Tm3+ Concentration and Temperature on Blue and NIR Upconversion Luminescence in Tm3+/Yb3+ Co-Doped NaY(WO4)2 Microstructures. AB - Tm3+/Yb3+ codoped NaY(WO4)2 microstructures with various Tm3+ concentrations and 10 mol% Yb3+ concentration were prepared by a microwave-assisted hydrothermal method, and their upconversion luminescence (UCL) was investigated. Under excitation at 980 nm, Tm3+/Yb3+ codoped NaY(WO4)2 exhibited strong blue and near infrared (NIR) emissions, respectively, corresponding to 1G4 --> 3H6 and 3H4 --> 3H6 transitions, with weak red emission due to the 1G4 --> 3H4 transition. The optimum doping concentrations of Tm3+ for the highest blue and NIR UCL were investigated, and it was found that the optimal concentrations for blue and NIR emissions were 0.5 mol% and 1.5 mol%, respectively. In addition, an analysis of temperature dependent blue and NIR UCL in both the samples with low and high Tm3+ concentrations, respectively, was undertaken. The results implied that the sample with low Tm3+ concentration displayed more obvious effect on the thermal quenching of 1G4 level. PMID- 27398501 TI - Effect of Nanohexaconazole on Nitrogen Fixing Blue Green Algae and Bacteria. AB - Nanohexaconazole is a highly efficient fungicide against Rhizoctonia solani. Nanoparticles are alleged to adversely affect the non-target organisms. In order to evaluate such concern, the present study was carried out to investigate the effect of nanohexaconazole and its commercial formulation on sensitive nitrogen fixing blue green algae (BGA) and bacteria. Various activities of algae and bacteria namely growth, N-fixation, N-assimilation, Indole acetic acid (IAA) production and phosphate solubilization were differently affected in the presence of hexaconazole. Although, there was stimulatory to slightly inhibitory effect on the growth measurable parameters of the organisms studied at the recommended dose of nanohexaconazole, but its higher dose was inhibitory to all these microorganisms. On the other hand, the recommended as well as higher dose of commercial hexaconazole showed much severe inhibition of growth and metabolic activity of these organisms as compared to the nano preparation. The uses of nanohexazconazole instead of hexaconazole as a fungicide will not only help to control various fungal pathogens but also sustain the growth and activity of these beneficial microorganisms for sustaining soil fertility and productivity. PMID- 27398502 TI - Highly Luminescent Carbon Dots Synthesized by Microwave-Assisted Pyrolysis and Evaluation of Their Toxicity to Physa acuta. AB - As a newly emerging class of nanomaterials, carbon dots have increasingly attracted researchers' attention. However, their potentially adverse environmental effects are yet largely unknown. In this work, the highly luminescent carbon dots were synthesized by microwave-assisted pyrolysis of tris(hydroxymethyl)aminomethane (Tris) and citric acid. Then acute and chronic toxicities of carbon dots to Physa acuta (P. acuta), as well as their effect on reproduction, were evaluated using the as-synthesized dots as an example. The quantum yield of the as-synthesized carbon dots was up to 53.5% excited at 360 nm with the most fluorescent fraction of 82.6% after simple purification by gel column. The results showed that no acute but chronic toxicities to P. acuta exposed to different treatment concentrations of the as-synthesized carbon dots were observed with dose- dependence. In addition, the fecundity of P. acuta was promoted significantly by the carbon dots at the concentrations of 0.5 and 1.0 mg/mL, yet inhibited at the concentration of 3.0 mg/mL after 12-day exposure. Mainly distributing in the visceral mass might be responsible for the effects of the carbon dots on the survival and fecundity of P. acuta. And there was no further evidence to confirm that the carbon dots can cause malformation in developing embryos. PMID- 27398503 TI - Degradation Characteristics of MgO Based Magnetic Tunnel Junction Caused by Surface Roughness of Ta/Ru Buffer Layers. AB - We investigated how surface roughness of a Ta/Ru buffer layer affects the degradation characteristics on MgO-based magnetic tunnel junctions (MTJs). MTJs with worse surface roughness on the buffer layer showed increased resistance drift and degraded time-dependent dielectric breakdown (TDDB) characteristics. We suggest that this resulted from reduced MgO thickness on the MTJ with worse surface roughness on the buffer layer, which was estimated by the TDDB and analytic approach. As a result, surface roughness of the buffer layer is a critical factors that impacts the reliability of MTJs, and it should be controlled to have the smallest roughness value as possible. PMID- 27398504 TI - Optical, Electrical, and Adhesive Properties of ZnO Thin Films. AB - ZnO films were sputtered onto glass substrates to thicknesses from 100 A to 500 A under the following conditions; (a) as-deposited films were maintained at room temperature (RT); (b) films were post-annealed at 150 degrees C for 1 h, and (c) films were post-annealed at 250 degrees C for 1 h. X-ray diffraction (XRD) result thus obtained demonstrate that ZnO has a wurtzite structure with a (002) texture diffraction peak with a 2theta of 34 degrees range. The intensity of the ZnO (002) peak increased with film thickness and upon post-annealing. As the ZnO thin film thickness increased and post-annealing was carried out, the grains became larger. A spectral analyzer was utilized to measure transmittance for various thicknesses. Post-annealing treatment promoted the growth of grains, yielding a large mean grain size and, therefore, low transmittance. The as deposited ZnO thin film with a thickness of 100 A had a transmittance maximum of approximately 88% and a reflectance minimum of around 12%. Additionally, the four point probe measurements revealed that p decreased as the ZnO thickness increased and with post-annealing treatment because grain boundaries and the surface of thin films scatter electrons, so thinner films have a greater resistance. ZnO with a thickness of 500 A that underwent post-annealing treatment at 250 degrees C had a minimum resistivity of 7.6 x 10-3 Omega . cm. Adhesion critically influences the surface energy of films. The surface energy of as-deposited ZnO films was higher than that following post-annealing treatments, revealing that the adhesion of the as-deposited ZnO films was stronger than that following post annealing treatment because the degree of crystallinity was lower. Accordingly, the thickness and crystallinity of ZnO importantly affects its optical, electrical, and adhesive characteristics. Finally, thinner as-deposited ZnO films exhibited better optical and adhesive properties. PMID- 27398505 TI - Investigation on the Charge Loss Mechanisms of Nanoscale Charge Trap Non-Volatile Memory by Using Stretched Exponential Function. AB - Charge loss mechanisms of nanoscale charge trap non-volatile memory devices are carefully examined and studied. Fowler-Nordheim tunnelling mechanism is used to perform rapid program/erase cycling. Based on the good fit of post cycled and baked threshold voltage data to Stretched Exponential function, the lowest point and the peak of Vt distribution were found to evolve in a similar manner that resulted to similar derived Ea. The saturation behaviour of the threshold voltage decay can be predicted and validated through cells' threshold voltage measurements that fit well to Stretched Exponential function. The power law relationship of program/erase cycle count and the saturation behaviour was found to be similar on the device under study and NROM devices that utilizes significant different charge injection mechanisms for program/erase operation. The experimental results also demonstrated that charge injection mechanism is one of the dominant factors in determining the underlying charge loss mechanism. Moreover, the determination of charge loss mechanism depends on the total charges injected through the tunnel oxide layer of ONO stack in NB-CTNVM cell. Physical interpretation of the experimental findings of the dominant charge loss mechanism is deliberated in detail. PMID- 27398506 TI - High Color-Rendering-index Hybrid White LEDs Employing CdSe/ZnS Core/Shell Quantum Dots. AB - Hybrid white LEDs were constructed by leveraging a combination of CdSe/ZnS core/shell QDs and YAG: Ce3+ phosphors. The CdSe/ZnS core/shell QDs were synthesized by a two-step process in which CdSe QDs were first prepared via a hot injection method, followed by ZnS coating through a facile single-molecular precursor approach. The resultant red-emitting CdSe/ZnS QDs showed decent fluorescent quantum yielding (36%). The resultant hybrid white LEDs--that based on CdSe/ZnS QDs and solid-state-reaction-processed YAG: Ce3+ phosphors--showed good luminescence properties, including bright warm light, a high color rendering index of 91.3, a low color temperature of 4965 K and a luminous efficiency of 44.22 lm/W. Moreover, increased luminous intensity has been observed in the presence of increased forward current without luminescence saturation, promising an ideal approach to construct warm-white LEDs with excellent color rendering properties. PMID- 27398507 TI - Nanocrystalline Gd2Ti2O7 Pyrochlore Material for NIR Reflective Pigment Application: Micro-Structural and Optical Studies. AB - In this interesting article, the synthesis of nanocrystalline Gd2Ti2O7 material by ball milling followed by annealing, characterization and its application are reported. The Rietveld structural refinement data confirm the cubic pyrochlore Gd2Ti2O7 phase with lattice parameter, a = 1.022(9) nm. The particle size observed by HRSEM image concurs with the average crystalline sizes of particles extracted from XRD data. The optical properties of pyrochlore nanocrystalline Gd2Ti207 material are explored from UV-visible, FT-IR, NIR, PL, and Raman spectroscopic measurements. From the present investigation, it is identified that the Gd2Ti2O7 nanopowder may be used as solar reflective as well as color pigment due to its high NIR reflectivity (85-95%) under the wavelength of 750-2500 nm. PMID- 27398508 TI - Structural, Optical and Magnetic Properties of Ni-Zn Ferrite Nanoparticles Prepared by a Microwave Assisted Combustion Method. AB - Ni-doped ZnFe2O4(Ni(x)Zn1-xFe2O4; x = 0.0 to 0.5) nanoparticles were synthesized by a simple microwave combustion method. The X-ray diffraction confirms the presence of cubic spinel ZnFe2O4for all compositions. The lattice parameter decreases with an increase in Ni content resulting in the reduction of lattice strain. High resolution scanning electron microscope images revealed that the as prepared samples are crystalline with particle size distribution in 40-50 nm range. Optical properties were determined by UV-Visible diffuse reflectance and photoluminescence spectroscopy respectively. The saturation magnetization (Ms) shows the super paramagnetic nature of the sample for x = 0.0-0.2, whereas for x = 0.3-0.5, it shows ferromagnetic nature. The Ms value is 1.638 emu/g for pure ZnFe2O4 sample and it increases with increase in Ni content. PMID- 27398509 TI - Facile Synthesis of Porous Mn2O3 Microspheres as Anode Materials for Lithium Ion Batteries. AB - Porous Mn2O3 microspheres with a diameter of 0.5-2 um were synthesized by a thermal decomposition of MnCO3 micospheres precursor. The effects of annealing time on the morphologies and electrochemical properties of the final products were systematically investigated. The porous Mn2O3 microspheres prepared at 600 degrees C for 4 h exhibit the best electrochemical properties with a high reversible capability (925 mAh/g at current density of 100 mA/g) and cycling stability. It still retains a high capacity of 565 mAh/g, even after 100 cycles, as anode materials for lithium-ion batteries. The good electrochemical performance for the porous Mn2O3microspheres can be attributed to its high surface area and mesoporous structure. PMID- 27398510 TI - A Tunable-Color Emission Phosphor Y2O3:Eu3+, Bi3+ with Efficient Energy Transfer for White Light Emitting Diodes. AB - The Eu3+, Bi3+ ions co-doped Y2O3 phosphor has been synthesized by the conventional solid-state reaction method, and its photoluminescence (PL) spectra are investigated for application in white light emitting diode (LED). The Eu3+, Bi3+ ions co-doped Y2O3 phosphor showed a characteristic emissions with greenish blue and red color upon the near-UV light in the range of 310-360 nm, originating from 3P1 --> 1S0 transition of Bi3+ and 5D0 --> 7F(J) transition of Eu3+, respectively. As 613-nm emission of Eu3+ ions is monitored, excitation spectrum consists of two broad peaks near 230 nm and 330 nm, ascribed to the Eu3+-O2- charge transfer band (CTB) and the transition from the ground state to the excited states of Bi3+ ions, respectively. It implies that the energy transfer from Bi3+ ions to E3+ ions occur and the phosphor's color may be controlled by adjusting the concentrations of Eu3+ ions and Bi3+ons in Y202O3The availability of this strategy is demonstrated in this work, and white light can be realized with superior chromaticity coordinates of (x = 0.337, y = 0.328) and a CCT of 5284 K for Y202O3% Eu3+3+0.1% Bi3+3+Thus, it will be a promising candidate for the ultraviolet excitation white light emitting diode (LED). PMID- 27398511 TI - InN Quantum Dot Based Infra-Red Photodetectors. AB - Self-assembled InN quantum dots (QDs) were grown on Si(111) substrate using plasma assisted molecular beam epitaxy (PA-MBE). Single-crystalline wurtzite structure of InN QDs was confirmed by X-ray diffraction. The dot densities were varied by varying the indium flux. Variation of dot density was confirmed by FESEM images. Interdigitated electrodes were fabricated using standard lithog- raphy steps to form metal-semiconductor-metal (MSM) photodetector devices. The devices show strong infrared response. It was found that the samples with higher density of InN QDs showed lower dark current and higher photo current. An explanation was provided for the observations and the experimental results were validated using Silvaco Atlas device simulator. PMID- 27398512 TI - Microwave Based Synthesis; Structural, Optical and Magnetic Measurements of Co2+ Doped MnFe2O4. AB - CO2+ doped manganese ferrite (Mn1-xCoxFe2O4, x = 0.0, 0.1, 0.2, 0.3, 0.4, 0.5) samples were synthesized by a microwave combustion method. Nitrates of the constituent elements and urea were respectively used as the oxidizer and fuel to drive the reaction. On an average a yield of 80% were obtained for all the compositions. Light-absorbing properties from UV-Vis diffuse reflection spectrum were studied and the results infer that the band gap energy (Eg) of the pure MnFe2O4 is 1.76 eV and with increase in C02+ ion concentration, it increases to 2.25 eV. The phase purity and crystal lattice symmetry were estimated from X-ray diffraction (XRD) and was identified as the spinel cubic crystal structure. The lattice parameter is found to decrease with an increase in Co content. The crystallite size was in the range of 19-25 nm. The purity and the composition of the elements were further confirmed by energy dispersive X-ray (EDX) results. Microstructural features obtained by scanning electron microscope (SEM) demonstrate that the nanocrystals were formed with a decrease in average grain size with C02+ content. Room temperature magnetic measurement for stoichiometric samples is discussed with the help of vibrating sample magnetometer (VSM). The saturation magnetization (M), remanant magnetization (Mr) and coercivity (H.) are measured from the respective hysteresis plots. PMID- 27398513 TI - Preparation and Photocatalytic of Nanoneedle Bi/ZnWO4by Two-Step Hydrothermal Method. AB - Nanoneedle Bi/ZnWO4 photocatalysts were successfully synthesized using a two-step hydrothermal method. In the first hydrothermal experiment ZnO/ZnWO4 nanoneedle crystals were synthesized from NaWO4. 2H2O and Zn(NO3)2. 6H2O, using polyacrylamide (PAM) as a template in a hydrothermal environment. Bi cations were then reduced by t-BuONa in a second hydrothermal experiment, adding nanoneedle ZnO/ZnWO4. The catalysts were then characterized by powder X-ray diffraction (XRD), scanning electron microcopy (SEM), energy dispersive spectrometer (EDS) and UV-vis diffuse reflectance spectrum (DRS). The results show that by adding Bi nanoparticles, the composition of the mixture gradually changed from that of ZnO/ZnWO4 to Bi/ZnWO4. The nanoneedle Bi/ZnWO4samples displayed better UV light photocatalysis than the nanoneedle ZnO/ZnWO4 samples. The optimum concentration of Bi was investigated using a photocatalytic experiment. A "blue shift" was observed when the molar ratio of Bi was increased. PMID- 27398514 TI - The Photoluminescence Properties of CaYAI3O7:Ce3+, Tb3+, Sm3+ Prepared by the Sol Gel Process. AB - This paper reports the synthesis and luminescence properties of rare earth doped CaYAI3O7 prepared via a sol-gel process. The phosphors have intense luminescence. In Ce3+/Tb3+ co-doped materials, there is energy transfer from Ce3+ to Tb3+ that enhances the luminescence of Tb3+. These materials may find applications in solid state lighting and radiation detection. PMID- 27398515 TI - Template-Assisting Preparation of Luminescent YAG:Nd3+ Nanoparticles and Hollow Nano-Beads. AB - Nanostructured YAG:Nd3+ is an interesting material with a wide range of applications. In this paper, we report the fabrication of luminescent YAG:Nd3+ nanoparticles via a simple template-assisting nano-casting technique. By optimizing the synthetic parameters, bead-like hollow YAG:Nd3+ nanoparticles with nano-porous walls were successfully prepared. Their porous and hollow structures, and strong photoluminescence in the "Human Optical Window" make the YAG:Nd3+ nanoparticles promising candidates for in-vivo applications. PMID- 27398516 TI - Density Functional Theory Study on the Interfacial Interaction of LiF (200) and Anatase TiO2(101). AB - Our recent experimental results have indicated that titanium dioxide (TiO2) mixed with LiF crystals show enhanced absorbance of the organic dye methylene blue. Prompted by these findings, in this study we have investigated the electronic properties of the surface of anatase TiO2(101) modified by a layer of LiF. Density functional theory (DFT) calculations have been carried out within the generalized gradient approximation (GGA) to accurately describe the electronic structure. From the calculation results we find that the addition of a layer of LiF greatly changes the electronic distribution of the surface of TiO2 (101). We believe this is because the close proximity of the layer of LiF to TiO2(101) facilitates charge polarization on the special O site of the TiO2surface. This confirms the theory that Li+ improves the absorbability of TiO2 through inducting special O sites on the TiO2surface. PMID- 27398517 TI - Nanoprecursor-Mediated Synthesis of Mg2+-Doped TiO2 Nanoparticles and Their Application for Dye-Sensitized Solar Cells. AB - Surface-doping anatase TiO2 nanoparticles with Mg2+ were prepared via a novel synthetic method, and used as photoanodes for dye-sensitized solar cells (DSSCs). X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) image results indicate that the Mg2+ doping has no effect on the crystal phase and morphology of anatase TiO2. The shift in XRD peaks to higher angles, the absorption shift in UV-vis diffuse reflection spectra, and X-ray photoelectron spectroscopy (XPS) results indicate the incorporation of Mg2+-ions into the TiO2 lattice. The as-prepared TiO2nanoparticles doped with a low concentration of ions is proven a superior photoanode material than pure anatase TiO2. The energy-conversion efficiency (1) of DSSC based on TiO2 nanoparticles doped with Mg2+ is at a maximum of 5.90%, corresponding to an efficiency improvement of 23.4% as compared to DSSC based on un-doped TiO2. This new synthetic approach using a nanoprecursor provides a simple and versatile method for the preparation of excellent photoanode materials for application in solar energy conversion devices. PMID- 27398518 TI - A Fluorescent Sensor Synthesized Using Silica Nanoparticles for Detecting Hg2+ in Aqueous Solution. AB - With the aim of detecting Hg2+ in aqueous solution, a new fluorescent nanosensor (RhB-APTES-SiNPs) for the determination of Hg2+ has been successfully developed. This senor was synthesized by immobilizing RhB-APTES on the surface of silica nanoparticles (SiNPs), which were prepared using the reverse microemulsion method. RhB-APTES-SiNPs can detect Hg2+ on-line, in real time and with the naked eye, thus providing "turn-on" fluorescence enhancement. The developed nanosensor exhibits highly sensitivity and selectivity over several cations in aqueous solution. Additionally, RhB-APTES-SiNPs exhibits an excellent ability to detect Hg2+ within a linear range from 1 to 6 uM, and its detection limit was calculated to be 0.5 ppb. PMID- 27398519 TI - Effect of Poloxamer on Zingiber Officinale Extracted Green Synthesis and Antibacterial Studies of Silver Nanoparticles. AB - The Zingiber officinale (Z. officinale) plant is one of the well-known medicinal plants. Poloxamer finds excellent clinical and therapeutic uses for curing of various ailments. The poloxamer 188 polymer and the plant extract of Z. officinale have been used to prepare the silver nanoparticles (AgNPs) by a green synthesis route. The Z. officinale plant extract has been used as a reducing agent, while the poloxamer 188 has been used as a stabilizing agent. The formation of face-centered cubic (fcc) structure AgNPs was confirmed by X-ray diffraction pattern. The effect of addition of poloxamer on the controlling the shape, size and morphologies of the AgNPs has been investigated by transmission electron microscopy (TEM) and dynamic light scattering techniques. The elemental composition of AgNPs was confirmed by energy dispersive X-ray (EDX) analysis. The anti-bacterial activity of AgNPs has been investigated using three human pathogens Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus. The poloxamer 188 protected AgNPs inhibit the bacterial growth more effectively than the pure Z. officinale extract and the Z. officinale extract AgNPs. PMID- 27398520 TI - Three-Dimensional Dielectrophoretic Microparticle Separator Fabricated by Ultraviolet-Assisted Direct-Write Assembly. AB - The design and fabrication of complex microfluidic devices is a subject of broad biomedical and technological interest. In this paper, we demonstrate the fabrication of a three-dimensional (3D) dielectrophoretic microparticle separator involving ultraviolet (UV)-assisted direct-write assembly of a UV-curable polyurethane. This approach yields a series of 3D microcoil interdigitated electrodes with defined geometry promoting particle separation through dielectrophoresis. These vertical microcoils give rise to considerable improvements in separation relative to standard planar (2D) microelectrodes. We envisage that the complex 3D electrodes will provide an enabling platform for a wide array of fluidic- and electronic-based applications. PMID- 27398521 TI - Simple, Selective and Sensitive Determination of CH3Hg+ Using Gold Nanocluster. AB - Mercury is a potent neurotoxin, which causes serious and permanent damage to biota including human beings. Nanomaterials like gold have been used to detect mercury, especially the mercuric ions in recent years, but few have been done on the determination of methylmercury (CH3Hg+). In this study, we present a simple, selective and sensitive method for the determination of CH3Hg+ co-existing with Hg2+ based on the fluorescence quenching of bovine serum albumin (BSA) stabilized gold nanoclusters (BSA-Au NCs). It was found that the fluorescence quenching of BSA-Au NCs by Hg2+ is stronger than CH3Hg+ at the same concentration. Hg2+ can be masked by EDTA while CH3Hg+ is less affected. Therefore, the determination of CH3Hg+ was achieved through EDTA masking. The detection limit for CH3Hg+ is 35 nmol/L after masking Hg2+ with EDTA. This method has been successfully applied to quantify CH3Hg+ in rice paddy water from Qingzhen, Guizhou and tap water from Beijing. PMID- 27398522 TI - Electrodeposition of Three Dimensionally Ordered Macroporous Germanium from Two Different Ionic Liquids. AB - Three dimensionally ordered macroporous (3DOM) Ge films have been made via ordered polystyrene (PS) templates by electrodeposition from ionic liquids 1 Butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) amide and 1-Ethyl-3 methylimidazolium tris (pentafluoroethyl) trifluorophosphate at room temperature. We discuss the possibility of obtaining high quality 3DOM Ge films from two different ionic liquids by the simple and inexpensive template-assisted electrochemical pathway. Scanning electron microscopy confirms the quality of the samples, and the optical measurements demonstrate that 3DOM Ge made electrochemically shows photonic crystal behavior. Such a material has the potential to make 3DOM Ge feasible for electrical, optical applications and for photonic crystal solar cells. PMID- 27398523 TI - Controlled Synthesis of Nanostructured Copper Oxides Through an Elaborate Solution Route. AB - Copper oxides (CuO) with hierarchical structures have been synthesized via a solution-based route with the assistance of sodium dodecyl sulfate (SDS). The size and morphology of obtained products could be rationally tuned through altering the molar ratio of starting materials. The composition of mixed solvent and the aging time were also found to influence the shape evolution of CuO particles. Based on the analyses of X-ray diffraction, scanning electron microscopy and transmission electron microscopy etc., a plausible mechanism was proposed for the formation of CuO hierarchical structures. UV-visible absorption study demonstrates their potential applications in optical electronic devices, and catalytic oxidation of formaldehyde shows their potential applications in catalytic degradation of volatile organic compounds. PMID- 27398524 TI - Combustion Synthesized Europium Doped LaAI11O18 Phosphors--An Electron Paramagnetic Resonance and Optical Study. AB - By adopting a facile solution combustion synthesis, crystallized europium doped blue phosphors were successfully prepared. These phosphors were characterized by X-ray diffraction (XRD), Fourier transform infrared absorption (FT-IR), energy dispersive analysis of X-ray, Electron Paramagnetic Resonance (EPR) and Photoluminescence (PL) experimental methods. The photoluminescence spectrum indicates Eu2+ and Eu3+ ions in these phosphors. The band at around 442 nm is attributed to the spin-allowed 4f65d1 (2D) --> 4f7(8S7/2) transition of Eu2+ ions. The sharp bands at 591 (5D0 --> 7F1) and 616 (5D0 --> 7F2) nm are attributed to the spin-forbidden transitions of Eu3+ ions. The EPR spectra of as prepared and post-treated LaAl11O18:Eu phosphors exhibit signals characteristic of La2+ and Eu2+ ions. The number of spins, Gibbs energy, magnetic susceptibility, Curie constant and effective magnetic moment values were calculated and compared at 296 and 110 K. PMID- 27398525 TI - TiO2/P3HT Hybrid Solar Cell with Efficient Interface Modification by Organic and Inorganic Materials: A Comparative Study. AB - TiO2/P3HT hybrid solar cells were fabricated by infiltrating P3HT into the pores of TiO2 nanowire arrays. CdS quantum dot and pyridine were employed to modify the interface of TiO2/P3HT before P3HT was coated. The results show that the interface treatment significantly enhanced the photovoltaic performance of the cell. However characterization of time-resolved photoluminescence, open-circuit voltage decay and transmission electron microscope analysis revealed that the underlying mechanism was different for the organic and inorganic interface modifications. Pyridine plays an important role in assisting the charge separation at the TiO2/P3HT interface, and suppressing electron back recombination. The reason for CdS modifying the cell in this way is mainly due to the suppression of electron back recombination, and the additional photovoltaic effect generated by CdS itself. PMID- 27398526 TI - Green Upconversion Emissions in Er3+/Yb3+ Co-Doped CaMoO4Prepared by Microwave Assisted Metathetic Method. AB - In this study Er3+ doped CaMoO4 (CaMoO4:Er3+), and Er3+/Yb3+-co-doped CaMoO4 (CaMoO4:Er3+Yb3+) nanoparticles have been synthesized by the microwave-assisted metathetic method. Er3+/Yb3+ co-doped CaMoO4 nanoparticles sintered at 600 degrees C showed the strongest photoluminescence intensity, and crystallized well. At the excitation of 980 nm, the CaMoO4 nanoparticles show the strongest green emission at the 520 nm and 550 nm emission bands. Moreover, the green light produced has a better color purity. PMID- 27398527 TI - Kinetic Research on Catalytic Degradation of Rhodamine B with Cobalt Phthalocyanine Supported Mg-Al Hydrotalcite. AB - Rhodamine B dye wastewater was degraded using cobalt phthalocyanine supported Mg Al hydrotal- cite and H2O2. The effects of H2O2, temperature and concentration of Rhodamine B on the reaction kinetics were studied. The results indicate that the degradation process conforms to the equation of first order kinetics. The fastest rate constant k observed was 66.2 x 10-4/min-1 at 62.5 degrees C, and the correlation coefficient R2 was 0.99733. PMID- 27398528 TI - Thickness Dependence Magnetization in Laser Ablated Ni-Cu-Zn Ferrite Nanostructured Thin Films. AB - Ni0.5Cu0.3Zn0.2Fe2O4 thin films with thickness ranging from 25 nm to 500 nm were grown on Si substrate using pulsed laser deposition technique and their structural and magnetic properties were investigated. From the atomic force microscopy (AFM) analysis, it is observed that the film roughness (Ra) depends strongly on the thickness of the fabricated film. The magnetizations of the thin films were found to decrease when the film thickness increases. The thinner films showed a larger magnetization than the thick films. All the films showed a blocking temperature indicating their superparamagnetic behavior. PMID- 27398529 TI - Anomalous Temperature-Dependent Upconversion Luminescence of alpha NaYF4:Yb3+/Er3+ Nanocrystals Synthesized by a Microwave-Assisted Hydrothermal Method. AB - Yb3+/Er3+co-doped cubic-(alpha-) phase NaYF4 nanocrystals were prepared through a microwave- assisted hydrothermal method. Temperature-dependent upconversion luminescence (UCL) and sensing properties were systematically studied. It is interesting that anomalous temperature- dependent UCL behavior is observed. With increasing temperature (303-573 K), the UCL intensity of Er3+ does not quench monotonously but reaches a minimum around 483 K and then increases. However, it was found that the UCL spectra change in a different way with decreasing temperature (573-303 K) from the one measured with increasing temperature. The fluorescence intensity ratio of 2H11/2 --> 4I15/2 to 4S3/2 --> 4I15/2 at any measured temperature point remains almost constant in all measurement processes, indicating the consistency of temperature in each spectrum measurement at all temperature points regardless of the heating or the cooling process in our experiments. The results demonstrate that NaYF4:Yb3+/Er3+ UC nanocrystal has good sensing stability and may have potential application in the nanoscale thermal sensor. PMID- 27398530 TI - Preparation, Energy Transfer Characteristics and Colorimetric Properties of Na2Dy4(WO4)7:Eu3+ Nanophosphors. AB - Eu3+-doped Na2Dy4(WO4)7 nanophosphors were synthesized via a co-precipitation method. The crystal structure and morphology of the nanophosphors were characterized by X-ray diffraction analysis and field emission scanning electron microscopy, respectively. For all Eu3+ doping concentrations, spherical particles with an average diameter of about 40 nm and consisting of a pure Na2Dy4(WO4)7 phase were obtained. The excitation and emission properties of the nanophosphors were examined by fluorescence spectroscopy and the energy transfer between Eu3+ and Dy3+ was studied. Furthermore, the influence of the Eu3+ concentration on the color coordinates and luminescence intensity is discussed. The nanophosphors could easily be excited by ultraviolet (UV) and near-UV light corresponding to the f-f transitions of Dy3+. The color coordinates of the nanophosphors light emission are in the white light region and the Commission Internationale de l'Eclairage (CIE) coordinates of the nanophosphors light emission varied between (0.331, 0.354) and (0.405, 0.368) depending on the Eu3+ doping concentration. PMID- 27398531 TI - Synthesis and Photoluminescent Properties of Eu2+-Doped BaSiF6 Nanoparticles. AB - By adjusting the molar ratio of oleic acid (OA), oleylamine (OM), and 1 octadecene (OD) ligands in reaction solution, Eu2+-doped BaSiF6 nanoparticles were synthesized using a thermal decomposition synthesis route. Eu2+ ions have been successfully doped into BaSiF6 host lattice and strong 4f-4f line emission of the Eu2+ in BaSiF6 matrix is observed. Meanwhile, the photoluminescent (PL) properties of BaSiF6:Eu2+ nanoparticles doping Eu2+ ions at different concentrations were also studied. PMID- 27398532 TI - A Novel and Facile Method to Prepare Integrated Electrospun Nanofibrous Membrane with Soldered Junctions. AB - Integrated electrospun nanofibrous membrane was prepared by creating soldered junctions between nanofibers via a facile strategy. Polyacrylonitrile (PAN) mixed with poly(vinylidene fluoride) (PVDF) at different ratios of PVDF were prepared in N,N'-dimethyl formamide (DMF), then electrospun to fabricate PAN/PVDF membranes. PVDF can form microgels in DMF which slows down volatile speed of DMF and affects the solidification of PAN/PVDF nanofibers. The resulting membranes were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy, dynamic water contact angle and tensile testing to confirm the morphology and mechanical properties. Soldered junctions were observed between nanofibers with the increase of PVDF content. These junctions made the membrane integrated and greatly enhanced tensile strength from 5.1 to 8.1 MPa (increased by ~60%) and tensile modulus from 49.4 to 117.9 MPa (increased by ~139%) without compromising porosity when the content of PVDF increased from 0 to 60 wt%. PMID- 27398533 TI - Colorimetric Detection of Cadmium Ions Using DL-Mercaptosuccinic Acid-Modified Gold Nanoparticles. AB - A colorimetric assay has been developed for detection of Cd2+ utilizing DL mercaptosuccinic acid-modified gold nanoparticles (MSA-AuNPs). The method showed good selectivity for Cd2+ over other metal ions. As a result, the linear relationships (r > 0.9606) between concentration 0.07 mM and 0.20 mM for cadmium ion were obtained. The detection limit was as low as 0.07 mM by the naked eye. The effect of pH on the aggregation was optimized. The MSA-AuNPs probe could be used to detect Cd2+ in an aqueous solution based on the aggregation-induced color change of MSA-AuNPs. PMID- 27398534 TI - Solvent-Assisted Preparation of High-Performance Mesoporous CH3NH3Pbl3 Perovskite Solar Cells. AB - Organometal trihalide perovskite based solar cells have attracted great attention worldwide since their power conversion efficiency (PCE) have risen to over 15% within only 3 years of development. Comparing with other types of perovskite solar cells, mesostructured perovskite solar cells based on CH3NH3Pbl3 as light harvesting material have already demonstrated remarkable advance in performance and reproducibility. Here, we reported a mesoscopic TiO2/CH3NH3Pbl3 heterojunction solar cell with uniform perovskite thin film prepared via solvent assisted solution processing method. The best performing device delivered photocurrent density of 20.11 mA cm-2, open-circuit voltage of 1.02 V, and fill factor of 0.70, leading to a PCE of 14.41%. A small anomalous hysteresis in the J V curves was observed, where the PCE at forward scan was measured to be 84% of the PCE at reverse scan. Based on a statistical analysis, the perovskite solar cells prepared by the reported method exhibited reproducible and high PCE, indicating its promising application in the fabrication of low-cost and high efficiency perovskite solar cells. PMID- 27398535 TI - Synthesis and Characterization of Zirconium Substituted Cobalt Ferrite Nanopowders. AB - Nanocrystalline ferrites; CoFe2O4 (CFO) and CoFe1.9Zr0.1O4 (CFZO) have been synthesized through chemical coprecipitation method. The role played by the zirconium ions in improving the magnetic and structural properties is analyzed. X ray diffraction revealed a single-phase cubic spinel structure for both materials, where the crystallite size increases and the lattice parameter decreases with substitution of Zr. The average sizes of the nanoparticles are estimated to be 16-19 nm. These sizes are small enough to achieve the suitable signal to noise ratio in the high density recording media. The increase in the saturation magnetization with the substitution of Zr suggests the preferential occupation of Zr4+ ions in the tetrahedral sites. A decrease in the coercivity values indicates the reduction of magneto-crystalline anisotropy. In the present study the investigated spinel ferrites can be used also in recoding media due to the large value of coercivity 1000 Oe which is comparable to those of hard magnetic materials. PMID- 27398536 TI - High Pseduo-Stoke's Shift of a Naphthalene-Bisindolylmaleimide Dye. AB - An energy transfer cassette was reported with energy donor and acceptor incorporated in one molecular. The two units (naphthalene and bisindolylmaleimide) were connected by covalent single bond. The intramolecular repulsion twisted the molecular conformation, thereby forcing the two units act as independent chromophores. Upon photoexcitation (lambda = 280 nm), bright emission peak was observed around 583 nm. The intramolecular cascade energy transfer from the naphthalene moiety to the bisindolylmaleimide framework is efficient and the efficiency is estimated to be 86%, providing large pseudo Stoke's shift (303 nm). At such a short separation, the orbital overlap interaction was completely isolated between chromophoric units. Computational study was carried out based on DFT. Further analysis of optimized structure and FMOs supports the efficient energy transfer in NBM. Favorable photophysical properties, such as efficient energy transfer, strong emission, and large Stoke's shift make it an attractive functional dye. PMID- 27398537 TI - Effect of Post Deposition Annealing Treatments on Properties of AZO Thin Films for Schottky Diode Applications. AB - High-quality aluminum (Al) doped ZnO (AZO) thin films were deposited on silicon substrates by RF sputtering at room temperature. The deposited films were annealed from the temperatures 350 degrees C to 650 degrees C in pure nitrogen (N2) ambient. The effects of annealing on the microstructural, optical and electrical properties of the AZO films were investigated. A detailed analysis by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Four Probe and Hall measurements was performed to study the properties of these AZO thin films. It was observed that all of the as-deposited and annealed AZO films have homogenous surfaces and hexagonal wurtzite structures with good crystalline quality. The study also suggested that there was an intermediate post annealing temperature (450 degrees C) at which the deposited ZnO film exhibit best surface characteristics. Pd/AZO Schottky devices were fabricated with 450 degrees C annealed AZO thin films and the parameters of Schottky devices were extracted from I-V characteristics. These results indicated that the Pd/AZO films were very much suitable for various optoelectronics applications particularly for metal semiconductor metal based UV detector application. PMID- 27398538 TI - A Rapid and Cost-Effective Laser Based Synthesis of High Purity Cadmium Selenide Quantum Dots. AB - A rapid and cost effective method is developed to synthesize high purity cadmium Selenide (CdSe) quantum dots in acetone medium using second harmonic of Nd:YAG nanosecond pulsed laser of 532 nm wavelength. The thermal agglomeration due the nanosecond pulse duration of the laser was successfully eliminated by using unfocussed laser beam and thereby providing a favorable conditions for the synthesis of quantum dots having the grain size of 3 nm. The morphological and optical characterizations like XRD, HRTEM, optical absorption of the synthesized CdSe quantum dots, reveal that the material possesses the similar characteristics of the one synthesized through cumbersome wet chemical methods. Relative to the CdSe bulk material, the synthesized CdSe quantum dots showed a blue shift in the measured band gap energy from near infrared spectral region to visible region, making this material very attractive for many solar energy harvesting applications like photo-catalysis and solar cells. PMID- 27398539 TI - Numerical Simulation on Optical Characteristics of ZnO/Cu/ZnO Thin Film. AB - This paper investigates optical characteristics of ZnO/Cu/ZnO multilayer optical thin film by numerical simulation and it is further verified by experiments. The influences of Cu and ZnO thickness on the optical characteristics of ZnO/Cu/ZnO thin films are studied. The results show that the transmittances of ZnO/Cu/ZnO thin film decrease with the increase of thickness of Cu layer but are nonlinear with the ZnO thickness. The maximal light transmission in the visible region is obtained by controlling the thickness of Cu and ZnO films. PMID- 27398540 TI - Cu-Cr-O Functionalized ETS-2 Nanoparticles for Hot Gas Desulfurization. AB - Engelhard Titanium Silicate-2 (ETS-2), a sodium nanotitanate, was surface functionalized by ion exchanging the solid with copper and chromium ions. The ability of this bi-metallic adsorbent to remove H2S at elevated temperatures was assessed using a dynamic breakthrough system and contrasted against an analogous mixed metal oxide, Cu-Cr-O. Unlike Cu-Cr-O, the H2S capacity for Cu-Cr-ETS-2 remains unchanged from 350 degrees C up to 950 degrees C. Using ETS-2 as a support for the metals increased the adsorbents surface area and improved its sulfur capacity from 35 mg H2S/g for Cu-Cr-O to 61 mg H2S/g adsorbent for CuCr ETS-2. The consistent presence of Cu9S5 on the sulfided adsorbents suggests that chromium effectively stabilizes the copper against reduction to metallic copper up to temperatures as high as 950 degrees C. PMID- 27398541 TI - Bioinspired One-Dimensional Nano-Wrinkles Guide Liquid Behaviors at the Liquid Solid Interfaces. AB - Learning from nature concerning how nanostructured surfaces interact with liquids may provide insight into better understanding of inside living biological interfaces bearing these nanostructures and further development of innovative materials contacting water. Here we investigate the dynamic behaviour of water droplet interacting with one-dimensional nano-wrinkles of different size on polydimethylsiloxane (PDMS) surface. The structure design of the variationally one-dimensional nano-wrinkles is inspired by in vivo responding topographic changes in aortic intima, which was characterized with liquid-phase atomic force microscopy. We show here that increasing the amplitude of the wrinkles promotes the spreading and energy dissipation of liquid droplets on the wrinkled interfaces. This result suggests a possible bio-protection mechanism of blood vessels via its structural changes on the aortic intima against elevated flowing blood, and provides a basis for tuning interfacial nanostructure of optimal durability against wearing by the liquid behaviors. PMID- 27398542 TI - Synthesis of Large Pore Carbon Nanoparticles for Removal of Malachite Green. AB - In this work, we have synthesized high surface area and large pore volume carbon nanoparticles (CNP) by a simple and easy sol-gel approach. The sol was prepared by mixing Pluronic F127 and phloroglucinol-terephthalaldehyde in acidic ethanol solution and the gel was formed after the vacuum removal of ethanol. In the sol gel process, hydrophobic segments of Pluronic F127 forms enhanced hydrogen bonding with trihydroxyl groups of phloroglucinol. A polymeric network of carbon precursor was also prepared by making the interconnectivity between four phloroglucinol and one terephthalaldehyde molecules. After thermal polymerization and carbonization of the gel, the CNP had a very high surface area (1441 m2 g-1) and large pore volume (1.7 cm3 g-1) with narrow micropore (1.0 nm) and mesopore (2.3 nm) diameters. The mesopore was developed due to the enhanced hydrogen bonding between Pluronic F127 and phloroglucinol, while the micropores were generated due to hydrocarbon polymeric network of phloroglucinol terephthalaldehyde. The CNP had a size about ca. 20 nm. The CNP were applied for the removal of the highly hazardous water pollutant malachite green (MG) and achieved a very high adsorption capacity (1892 mg g-1). The commercials powder activated carbon (PAC) was also applied for the removal of MG and achieved an adsorption capacity of PAC was 1390 mg g-1. It believes that shape and size of CNP and PAC played an important role in the adsorptive removal of MG. PMID- 27398543 TI - Fabrication and Magnetic Properties of Sn-Doped ZnO Microstructures via Hydrothermal Method. AB - Pure zinc oxide (ZnO) and Sn-doped ZnO hexagonal sheets were synthesized by template free hydrothermal growth mechanism with controlled morphology by using zinc acetate dihydrate (Zn(CH3COO)2. 2H2O), tin chloride pentahydrate (SnCl4 . 5H2O), Polyvinylpyrrolidone (PVP) and H2O as precursors. The structural, physical, chemical, and magnetic characteristics were investigated by X-ray diffraction, field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy and alternating gradient magnetometer (AGM), respectively. The average crystalline size of hexagonal phase of ZnO sheets was calculated to be about 34 nm from XRD patterns. Energy dispersive spectroscopy provided the compositional analysis of pure and Sn-doped ZnO. Room temperature ferromagnetism (RTFM) was observed by AGM for pure and Sn-doped ZnO hexagonal plates. RTFM increases monotonically for Sn doping and reaches maximum saturation magnetization 0.045 emu/g for 3% Sn-doped ZnO. PMID- 27398545 TI - Novel Organic Semiconductors Based on Phenyl and Phenylthienyl Derivatives for Organic Thin-Film Transistors. AB - New phenyl and phenylthienyl derivatives end-functionalized with carbazole and alpha-carboline, 9-(4- (9H-carbazol-9-yl)phenyl)-9H-carbazole, 9-(4-(9H-carbazol 9-yl)phenyl)-9H-pyrido[2,3-b]indole, 9-(3-(9H-carbazol-9-yl)phenyl)-9H-carbazole, 9-(3-(9H-carbazol-9-yl)phenyl)-9H-pyrido[2,3-b]indole, 9-(4-(5-(9H-carbazol-9 yl)thiophen-2-yl)phenyl)-9H-carbazole, and 9-(3-(5-(9H-carbazo-9-yl) thiophen-2 yl)phenyl)-9H-carbazole were synthesized and characterized as organic semiconductors for organic thin-film transistors (OTFTs). Most compounds exhibited p-channel characteristics with carrier mobility as high as 1.7 x 10-5 cm2/Vs and a current on/off ratio of 102-104 for top-contact/bottom-gate OTFT devices. PMID- 27398544 TI - Homogeneous Dispersion of Carbon Nanotubes on Surface-Modified Bulk Titanium Substrates by Thermal Chemical Vapor Deposition. AB - Catalytic syntheses of CNTs on the pristine Ti mesh, the pristine Ti plate and the etched Ti plate have been conducted using thermal chemical vapor deposition (CVD) with Fe catalysts. Surface of the pristine Ti plate was etched in a sulfuric acid (H2SO4) solution to facilitate the uniform dispersion of Fe catalysts. The surface of Ti substrates, the distribution and the composition of catalysts, and the structure and dispersion of the CNTs were examined using Scanning electron microscope (SEM), transmission electron microscope (TEM), atomic force microscope (AFM), electron probe micro-analysis (EPMA) and Micro Raman spectroscopy. Fe catalysts were dispersed uniformly on the surface of the etched Ti plate indicating that Surface modification by etching was effective. CNTs on the pristine Ti mesh and the etched Ti plate are more densely populated and have smaller diameters than CNTs on the pristine Ti plate. These results can be attributed to smaller Fe catalysts more homogeneously distributed on the pristine Ti mesh and the etched Ti plate. The calculated I(G)/I(D) ratios of 1.02 and 0.97 for CNTs on the pristine Ti mesh and the etched Ti plate, respectively, indicate a high degree of structural disorders on CNTs. PMID- 27398546 TI - Optimal Geometry Aspect Ratio of Ellipse-Shaped- Surrounding-Gate Nanowire Field Effect Transistors. AB - Theoretically ideally round shape of the surrounding gate may not always guarantee because of limitations of the fabrication process in surrounding-gate nanowire field effect transistors (FETs). These limitations may lead to the formation of an ellipse-shaped surrounding gate with major and minor axes of different lengths. In this paper, we for the first time study the electrical characteristics of ellipse-shaped-surrounding-gate silicon nanowire FETs with different ratio of the major and minor axes. By simultaneously simulating engineering acceptable magnitudes of the threshold voltage roll-off, the drain induced barrier lowering, the subthreshold swing, and the on-/off-state current ratio, an optimal geometry aspect ratio between the channel length and the major and minor axes of the ellipse-shaped-surrounding-gate nanowire FET is concluded. PMID- 27398548 TI - Ferromagnetic and Photocatalytic Properties of Layered Perovskite LaBaCo2O6 Nanostructures. AB - Cationic ordered layered tetragonal perovskite phase LaBaCo2O6 (LBCO) nanomaterials with irregular shape, and an average diameter of about 100 nm were successfully prepared. A precursor material was annealed in an argon atmosphere at 1100 degrees C for 48 hours, and then heat treated in an oxygen atmosphere pressure at 800 degrees C for 12 hours. The resulting LBCO nanomaterials show ferromagnetic transition at about 175 K without any structural changes. They show metallic behavior at below 140 K, and adopt the behavior of soft ferromagnetic materials at 80 K. Cationic ordered LBCO nanomaterials display photocatalytic activities, as they successfully degrade MB solutions under both UV irradiation and visible light. The B-site cations act as the active center, and are located in the centre of BO6 octahedron units. The various valence states of Co ions in LBCO could contribute to the enhancement of photocatalytic activies. PMID- 27398547 TI - Synthesis and Characterization of Benzothiadiazole Derivatives as Organic Semiconductors for Organic Thin-Film Transistors. AB - New benzothiadiazole derivatives end-functionalized with carbazole and a carboline, 4,7-di(9H-carbazol-9-yl)benzo[c][1,2,5]thiadiazole (1) and 4-(9H carbazol-9-yl)-7-(9H-pyrido[2,3-bindol-9-yl) benzo[c][1,2,5]thiadiazole (2) were synthesized and characterized as organic semiconductors for organic thin-film transistors (OTFTs). Thermal, optical, and electrochemical properties of the corresoponding compounds were characterized. Thin films of compound 1 exhibited p channel characteristics with carrier mobility as high as 10-4 cm2/Vs and a current on/off ratio of 105 for top-contact/bottom-gate OTFT devices. PMID- 27398549 TI - Surface-Enhanced Raman Scattering from Au-Nanorod Arrays with Sub-5-nm Gaps Stuck Out of an AAO Template. AB - Ordered arrays of Au-nanorod-tips protruding from an anodic aluminum oxide (AAO) template are reported as reproducible and active surface-enhanced Raman scattering (SERS) substrates. The Au-nanorods were grown in the nanochannels of the AAO template by use of alternative current electrodeposition, then the template was strengthened using a polymer, and finally the template bottom side was selectively etched to expose the Au-nanorod tips. By controlling the thinning of the AAO-porewalls, the inter-nanorod-gaps were tuned to ~5 nm, forming dense and uniform nano-gap induced "hot spots" among the adjacent Au-nanorod tips. As a result, the electromagnetic field of the Au-nanorod-tip arrays was uniformly enhanced, and demonstrated high SERS sensitivity with good signal reproducibility. The Au-nanorod-tips have the potential to be used in SERS-based applications in order to rapidly detect trace pollutants in the environment. PMID- 27398550 TI - Egg White Templated Synthesis of Ag and Au@Ag Alloy Microspheres for Surface Enhanced Raman Spectroscopy Research. AB - Herein, we report the green synthesis of Ag and Au@Ag microspheres by using the aqueous extracts of the egg white as well as their application as substrates for surface-enhanced Raman spectroscopy (SERS) detection. Both microspheres are prepared via the green synthesis method (room temperature, in aqueous solution and a benign reducer). The as-prepared urchin-like Ag microspheres have an average diameter of 600-800 nm, which is made up of some nanopricks with an average length of 10-40 nm. Meanwhile, the Au@Ag architectures prepared by galvanic replacement keep nearly similar size, which is also composed of some compact nanoparticles with an average diameter of about 10-40 nm. These products are characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electronic microscopy (TEM), and Fourier transform infrared spectrophotometer (FTIR). The study on SERS activities is also carried out for both microspheres. It is found that Au@Ag microspheres possess much higher SERS activity than Ag microspheres. Our work may shed light on the design and synthesis of self-assembled 3D micro/nano-architectures for the use of SERS, catalysis, biosensors, nanomedicine, etc. PMID- 27398551 TI - Production of Nanofibers Containing the Bioactive Compound C-Phycocyanin. AB - C-phycocyanin (C-PC) is a water-soluble phycobiliprotein present in light harvesting antenna system of cyanobacteria. The nanostructures have not been widely evaluated, precluding improvements in stability and application of the C PC. Electrospun nanofibers have an extremely high specific surface area due to their small diameter, they can be produced from a wide variety of polymers, and they are successfully evaluated to increase the efficacy of antitumor drugs. The incorporation of C-PC into nanofibers would allow investigations of potential uses in alternative cancer treatments and tissue engineering scaffolds. In this paper, C-phycocyanin were incorporated into the polymer polyethylene oxide (PEO) in various concentrations for nanofiber production via an electrospinning process. Nanofibers structures were analyzed using digital optical microscopy and scanning electron microscopy (SEM). Thermogravimetric analysis was performed on the pure starting compounds and the produced nanofibers. At a concentration of 2% (w/w) of PEO, nanofibers were not produced, and concentrations of 4% (w/w) of PEO failed to produce nanofibers of good quality. Solutions with 6% (w/w) PEO, 6% (w/w) PEO plus 1% (w/w) NaCI, and 8% (w/w) PEO promote the formation of bluish, homogeneous and bead-free nanofibers with average diameters varying between 542.1 and 759.9 nm, as evaluated by optical microscopy. SEM analysis showed that nanofibers produced from polymer solutions containing 6% (w/w) PEO, 1% (w/w) NaCl and 3% (w/w) C-PC have an average diameter of 295 nm. Thermogravimetric analysis detected an increase in thermal resistance with the incorporation of C phycocyanin into nanofibers. PMID- 27398552 TI - Electrodeposition of Fe3O4 Thin Film and Its Application as Anode for Lithium Ion Batteries. AB - Fe3O4 films were prepared by electrodeposition under varying preparation conditions (current density, temperature, and time). The electrodeposited Fe3O4 were characterized in terms of morphology and composition using scanning electron microscopy (SEM) and X-ray diffraction (XRD). The electrodeposited films were also tested as anode in coin cell systems. Fluoroethylene carbonate (FEC) electrolyte was found to improve the battery performance due to formation of a better solid electrolyte interface (SEI). Conducting polymer of polypyrrole (PPY) was coated on the surface of Fe3O4 films for the first time with the aim to improve the electric conductivity and to buffer volume expansion of Fe3O4 films. PMID- 27398553 TI - Electro-Spun Poly(vinylidene fluoride) Nanofiber Web as Separator for Lithium Ion Batteries: Effect of Pore Structure and Thickness. AB - Electro-spun nanofiber web is highly attractive as a separator for lithium ion batteries because of its high electrical properties. In moving toward wider battery applications of the nanofiber separators, a deeper understanding on the structure and property relationship is highly meaningful. In this regard, we prepared electro-spun poly(vinylidene fluoride) (PVdF) webs with various thicknesses (10.5~100 um) and investigated their structures and electrochemical performances. As the thickness of the web is decreased, a decrease of porosity and an increase of pore size are resulted in. For the 10.5 um-thick separator, a minor short-circuit was detected, stressing the importance of reducing pore-size on prevention of short-circuit. However, above the thickness of 21 um, well connected, submicron-sized pores are generated, and, with lowering the separator thickness, discharge capacity and rate capability are enhanced owing to the lowered area-specific resistance. PMID- 27398554 TI - CeO2-Co3O4/CuO Catalysts with Chrysanthemum-Like Morphology for Preferential CO Oxidation. AB - Inverse CeO2-Co3O4/CuO catalysts with chrysanthemum-like morphology were prepared by the co-precipitation method, and characterized via scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), temperature-programmed reduction (H2-TPR), and N2 adsorption-desorption techniques. It is found that the filament is composed of ordered-array CuO nanocrystallites, and CeO2 was dispersed on the outer surface of filament. The CeO2-Co3O4/CuO catalyst with thin filaments can form the long periphery at the CeO2-CuO contact interface and improve catalytic performance. Therefore, the CAT 350 catalyst with the thinnest filaments presents the highest catalytic activity among the as-prepared catalysts. PMID- 27398555 TI - Crystal Structure Determination of the S/TiO2 System and the Correlation with Its Photocatalytic Properties. AB - A sulfur doped anatase photocatalyst was synthesized through a microwave-assisted sol-gel method and posteriorly, it was characterized using X-ray diffraction by powders (XRD) and High Resolution Electron Microscopy (HREM). Morphology and average size of the crystallite were determined for the sample, preferential crystal orientation was also analyzed and all these structural features were related to the photocatalytic properties. Moreover, a pure TiO2 sample was also obtained by the same synthesis method and it was used as a reference, and its structure and photocatalytic properties were compared to those observed for the sulfur doped anatase. The structural analysis showed similar results for both sample types but, photocatalytic properties are rather different. A small difference in chemical composition had an impact in the catalytic properties. PMID- 27398556 TI - Study of Self-Induced Growth of AlGaAs Nanoneedles on Silicon Substrates Using Metal Organic Chemical Vapor Deposition Technique. AB - A simple catalyst free growth method was used for the growth of single crystalline AlGaAs nanoneedles on Si substrate by metal organic chemical vapor deposition (MOCVD) technique. The growth mechanism of catalyst free growth of nanoneedles was investigated. The effect of growth rate, growth temperature and V/III ratio was studied in detail. The growth of nanoneedles required a careful optimization of the growth conditions. The formation of well-faceted nanoneedles with hexagonal cross-section was found to be influenced by the growth parameters. Based on these studies, the growth mechanism has been explained using nucleation theory. The growth of nanoneedles was believed to proceed via Vapor-Solid (VS) growth mechanism after the initial AlGaAs cluster formation depending on the growth conditions. PMID- 27398557 TI - Effect of Solvent-Assisted Dispersions of Clay/Epoxy Nanocomposites on Steel Passivation. AB - Dispersion of clay in polymer matrices is important to improve their engineering performances. Here we report the effect of solvent on dispersion of montmorillonite (MMT) in an epoxy matrix by examining transmission electron micrographs and X-ray diffraction of MMT/epoxy composites prepared with solvents with different polarities. We found that N-metyl-2-pyrrolidone (NMP) used as a polar solvent exhibited the improved dispersion of MMT in the epoxy owing to positive interaction energies with components, which prevents the aggregation of MMT platelets. The solvent-assisted dispersion of MMT significantly increased the corrosion resistance of MMT/epoxy nanocomposites pre-coated onto steel plates. PMID- 27398558 TI - Synthesis and Characterization of Fe2(MoO4)3Nano-Photocatalyst by Simple Sol-Gel Method. AB - Ferric molybdate (Fe2(MoO4)3) nanorods (NRs) were successfully synthesized using metal nitrates, citric acid and ethyl cellulose by a simple sol-gel method. Structural, morphological, optical and magnetic properties of the obtained powder were characterized by powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectra, high resolution scanning electron microscope (HR-SEM), energy dispersive X-ray (EDX), UV-Visible diffuse reflectance spectra (DRS), photoluminescence (PL) spectra and vibrating sample magnetometer (VSM). XRD results indicated that the resultant powder was pure single phase crystalline with monoclinic structure. FT-IR spectra indicate the type of bonds between metals and oxygen. HR-SEM images shows that the morphology of the powder consist with well defined nanorods (NRs) structure. VSM results showed ferromagnetic behavior. The addition of TiO2 catalyst, it enhanced the photo-catalytic activity of Fe2(MoO4)3. The mixed oxide catalyst of Fe2(MoO4)3-TiO2 nano-composites (NCs) were also tested for the photocatalytic degradation (PCD) of 4-chlorophenol (4 CP). It was found that the PCD efficiency of Fe2(MoO4)3 NCs is higher than pure Fe2(MoO4)3 and TiO2 catalysts. PMID- 27398559 TI - Growth and Magnetic Characterization of 1D Permalloy Nanowires Using Self Developed Anodic Aluminium Oxide Templates. AB - 1D Permalloy refers to arrays of nanowires (NWs) made of an alloy of Ni and Fe with 80 and 20 at% composition respectively. In the present work 1 D Permalloy NWs arrays were fabricated into the pores of self engineered Anodic Aluminium Oxide (AAO) templates by a simple electrodeposition technique (EDT). By varying the anodization voltage and parameters of the electrolyte solutions we developed AAO templates with different average pore diameters (40 nm to 70 nm) and developed 1D Permalloy NWs within them. Structural characterization of AAO templates and 1D Permalloy NWs were performed by Transmission and Scanning Electron Microscopy (TEM and SEM respectively). X-ray diffraction (XRD) studies of 1D Permalloy NWs showed their fcc crystalline structure and the AAO template was found to be amorphous in nature. Magnetic studies showed the 1D Permalloy NWs arrays to have strong shape anisotropy, and the easy axis was found to be parallel to the NWs axis. We studied the angular dependence of magnetic properties of the NWs. Coercivity (Hc) and remanence (Mr/Ms) measured along the NWs axis were found to be higher than those measured in a direction perpendicular to the NWs axis. 1D Permalloy NWs developed in this work have the potential to be used in magnetic recording devices. PMID- 27398560 TI - Antimicrobial Efficacy of Synthesized Quaternary Ammonium Polyamidoamine Dendrimers and Dendritic Polymer Network. AB - Water treatment to mitigate microbial contaminants is a major challenge across globe paving the way to develop novel antimicrobial compounds. We aim at architecting antibacterial moiety eventually catering to vast water treatment industry. In this research study, quaternary ammonium functionalized polyamidoamine (PAMAM) dendrimer and PAMAM-ethyleneglycol dimethacrylate (EGDMA) dendritic polymer network were synthesized. These materials were characterized by various analytical techniques like ATR-FTIR, 1HNMR, DSC etc. Water soluble generation (G) 1.0 PAMAM dendrimer and water insoluble PAMAM G1.0 EGDMA dendritic polymer network were quaternized by reacting with dilute hydrochloric acid (HCI) and octyl iodide (01) respectively. Both quaternary ammonium dendrimer products were found to exhibit potent bactericidal activity against a group of common Gram negative and Gram-positive bacteria. 10 mg/L concentration of liquid PAMAM G1.0 QHCI was efficient to kill 100% bacteria rapidly within an incubation time of just 2 minutes. In addition, quaternary ammonium dendritic polymer network PAMAM G1.0-EGDMA Q OI demonstrated good contact killing antimicrobial property without releasing any active molecule into the surrounding medium and disinfected contaminated water within 5 minutes. Both quaternary ammonium dendrimer and dendritic polymer network showed negligible cytotoxicity in MTT assay indicating their potential as a viable antimicrobial agent. PMID- 27398561 TI - Sensitivity and Response of Polyvinyl Alcohol/Tin Oxide Nanocomposite Multilayer Thin Film Sensors. AB - Nanocrystalline Tin Oxide (SnO2) is Non-Stoichiometric in Nature with Functional Properties Suitable for gas sensing. In this study, SnO2nanoparticles were prepared by the sol-gel technique, which were then characterised using X-ray diffraction. The nanoparticles showed tetragonal structure with an average crystallite size of 18 nm. The stretching and vibration modes of SnO2were confirmed using Fourier transform infrared spectroscopy. The size of SnO2 nanoparticles was determined using particle size analyser, which was found be 60 +/- 10 nm on average. The surface morphology of the nanoparticles was investigated using scanning electron microscope, which showed irregular-sized agglomerated SnO2nanostructures. In addition, primary particle size was evaluated using high-resolution transmission electron microscopy, which was found to be 50 nm on average. The polyvinyl alcohol/SnO2 composite thin film was prepared on a glass substrate using spin-coating method. The values of band gap energy and electrical conductance of 13-layer thin film were found to be 2.96 eV and 0.0505 mho, respectively. Sulfur dioxide (SO2) was suitably tailored to verify the sensor response over a concentration range of 10-70 ppm at room temperature. The performance, response, and recovery time of sensors were increased by increasing the layers of the thin film. PMID- 27398562 TI - Influences of Co Doping Effect on the Structural Properties of a Single Graphene Film. AB - The effect of cobalt doping on the structural properties of a single graphene film were determined by use of SEM, temperature-dependent Raman technique, XRD and XPS measurements. XRD and SEM measurements revealed that Co nanoparticles formed on the surface of the single layer of graphene. The XPS results also revealed the existence of bivalent Cobalt ions. Raman spectroscopy revealed enhanced disorder effects, and a large red shift in the 2D peak after the Co deposition process. With decreasing temperature of the pristine single graphene film, the G peak stiffened and sharpened. In contrast, the G peak of the graphene film after Co deposition was not dependent on temperature. This phenomenon indicates that the inhomogeneous local disorder effect is induced by the Co atoms embedded in the graphene film. Moreover, a larger disorder effect induced by Co deposition can be found in single graphene films with higher original vacancies, suggesting the possible formation of Co atom-vacancy complexes. The magnetic Co nanoparticles and magnetic Co atom-vacancy complexes in graphene produced in this experiment could be used in graphene-based spintronic device applications. PMID- 27398563 TI - Multi-Walled Carbon Nanotube Functionalization by Radical Addition Using Hydroxymethylene Groups. AB - Synthetic methodology and characterization of multi-walled carbon nanotubes (MWCNTs) function- alized with hydroxymethylene groups are reported. The MWCNTs were synthesized by the spray pyrolysis technique using toluene as carbon source and ferrocene as catalyst. Hydroxymethylation of MWCNTs was carried out by methanol using benzoyl peroxide (BPO) at different quantities (300 to 900 mg); the optimum BPO quantity was 300 mg. The resulting materials were characterized by FT-IR, Raman Spectroscopy, Thermal Gravimetric Analysis (TGA) and Transmission Electron Microscopy (TEM). The presence of the hydroxymethylene group on the MWCNTs surface was demonstrated by FT-IR, Raman Spectroscopy, TGA, EDS, TEM and Mass Spectrometry. The func- tionalized MWCNTs were not damaged by this methodology. PMID- 27398564 TI - Dependence of Thermal Conductivity on Thickness in Single-Walled Carbon Nanotube Films. AB - Herein, we report experimentally dependence of thermal conductivity on thickness of single walled carbon nanotubes (SWNTs) thin films; the measurements are based on the micropipette thermal sensor technique. Accurate and well resolved measurements of thermal conductivity made by the micropipette sensor showed a correlated behavior of thickness and thermal conductivity of CNT films that thermal conductivity decreased as thickness increased. The thickness dependence is explained by reduction of mean free path (MFP), which is induced by more intertubular junctions in more dense-packed carbon nanotube (CNT) networks; the thicker SWCNT films were revealed to have higher density. PMID- 27398565 TI - Flexible and Conducting Carbon Nanofibers Obtained from Electrospun Polyacrylonitrile/Phosphoric Acid Nanofibers. AB - We report on the feasible synthesis of flexible and conductive carbon nanofibers by electrospinning process using polyacrylonitrile (PAN) and phosphoric acid (PA) as precursors. The carbon nanofibers were subsequently obtained by stabilization and carbonization of the electrospun PAN nanofibers. From SEM data, it was found that the electrospun PAN nanofibers showed a smooth surface and had an average diameter of approximately 200 nm. Afterwards, the electrospun PAN nanofibers were stabilized at 250 degrees C and heated at 900 degrees C for the carbonization process to obtain the carbon nanofibers. The carbonized PAN nanofibers exhibited a drastic improvement of electrical conduction. From Raman spectroscopy data, it was found that the carbonization at 900 degrees C gave a decrease of the intensity ratio of D and G peaks, indicating higher graphitic structure. PMID- 27398566 TI - Heat-Induced Agglomeration of Amorphous Silicon Nanoparticles Toward the Formation of Silicon Thin Film. AB - The thermal behavior of silicon nanoparticles (Si NPs) was investigated for the preparation of silicon thin film using a solution process. TEM analysis of Si NPs, synthesized by inductively coupled plasma, revealed that the micro-structure of the Si NPs was amorphous and that the Si NPs had melted and merged at a comparatively low temperature (~750 degrees C) considering bulk melting temperature of silicon (1414 degrees C). A silicon ink solution was prepared by dispersing amorphous Si NPs in propylene glycol (PG). It was then coated onto a silicon wafer and a quartz plate to form a thin film. These films were annealed in a vacuum or in an N2 environment to increase their film density. N2 annealing at 800 degrees C and 1000 degrees C induced the crystallization of the amorphous thin film. An elemental analysis by the SIMS depth profile showed that N2annealing at 1000 degrees C for 180 min drastically reduced the concentrations of carbon and oxygen inside the silicon thin film. These results indicate that silicon ink prepared using amorphous Si NPs in PG can serve as a proper means of preparing silicon thin film via solution process. PMID- 27398567 TI - Preparation of Ni-Doped CeFeO3 by Microwave Process and Its Visible-Light Photocatalytic Activity. AB - Using Ce(NO3)3. 6H2O, Fe(NO3)3. 9H2O and Ni(NO3)3. 6H2O as the main raw materials, nano Ni-doped CeFeO3 was prepared by the microwave method for the first time. The Ni-doped CeFeO3samples were characterized by XRD, SEM, DRS and EDS. The results show that Ni-doped CeFeO3exhibits a perovskite structure (ABO3), and contains nanosheets less than 10 nm thick. The prepared nanosheets have an optical band gap of 1.93 eV. The effect of different doping amounts on the photocatalytic properties of Ni-doped CeFeO3 was studied under visible light, using methyl-orange. When the concentration of the methyl-orange solution was 10 mg/L, and the illumination time allowed for photocatalysis was 90 min, the degradation rate rose to nearly 98%. Moreover, Ni-doped CeFeO3 has a higher photocatalytic activity than pure CeFeO3 powder, making it suitable for a broad range of applications. PMID- 27398568 TI - Scaffolds Containing Spirulina sp. LEB 18 Biomass: Development, Characterization and Evaluation of In Vitro Biodegradation. AB - Polymer nanofibers are nanomaterials that can be used as scaffolds in tissue engineering. The objective of this study was to develop, characterize and evaluate the in vitro degradation of a biomaterial consisting of nanofibers produced from biodegradable and biocompatible polymers with potential applications as a scaffold for tissue regeneration and containing Spirulina sp. LEB 18 biomass as the bioactive compound. The polymers used were poly(hydroxybutyrate-co-hydroxyvalerate) and polycaprolactone. The polymeric solutions exhibited sufficiently high viscosity to produce uniform nanofibers with diameters between 335 and 617 nm. The applied conditions were as follows: a voltage of 25 kV, a distance from the capillary to the collector of 120 mm, a capillary diameter of 0.80 mm, and 12% polycaprolactone and a blend of 5% polycaprolactone and 10% poly(hydroxybutyrate-co-hydroxyvalerate). The biomass was incorporated into the nanofibers at a concentration of 3%, and the incorporation was confirmed using confocal microscopy. The nanofibers were characterized using differential scanning calorimetry and thermogravimetric analysis, which showed that the addition of biomass did not alter the thermal properties of the biomaterial. The addition of biomass improved the tensile strength and elongation of the scaffolds compared with those produced with polymers alone. A biodegradation assay showed enzymatic action toward the biomaterial, simulating the behavior of natural tissue. Based on the analysis, it was concluded that the scaffolds that were produced have the potential to be applied in the field of tissue regeneration as biomaterials with pharmacological properties. PMID- 27398569 TI - Study on Photocatalytic Degradation of 2,4-Dichlorophenol by ZnS Microsphere. AB - The self-supported ZnS microsphere composed of interwoven nanosheets was synthesized by hydrothermal method. The as-prepared ZnS powders were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The photocatalytic activity of the fabricated ZnS powders was evaluated by the degradation of 2,4-dichlorophenol (DCP) under UV light. Effects of DCP initial concentration, ZnS dosage, solution pH, light source, and dissolved oxygen on DCP photocatalytic degradation efficiency were investigated and optimized systematically. Results demonstrated that 53% of DCP could be effectively degraded under the optimal experimental conditions. Finally, high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the degradation products. Based on the experimental results obtained, a prob- able degradation pathway was proposed. PMID- 27398570 TI - Optical Properties and Aggregation of Graphene Nanoplatelets. AB - In the present paper, the optical density of dispersions of randomly oriented multilayer graphene nanoplatelets (GNPs) was estimated. Calculated and experimental data were compared for aqueous GNP dispersions stabilized with various surfactants. It was shown that the sonication of an expanded graphite compound (EGC) in aqueous surfactant solutions leads to the transformation of EGC worm-like particles into weak GNP aggregates which are able to pass into solution upon dilution and agitation of the system. They may be filtered and washed out of surfactants. The concentrated GNP dispersions containing these weak aggregates can be used to synthesize different graphene-based nanostructures and obtain novel composite materials. PMID- 27398571 TI - Optimization of Parameters to Achieve High Yield and Purity Single-Walled Carbon Nanotube by Thermal and Chemical Oxidation and Its Effect on Conductivity. AB - Single wall carbon nanotubes due to their unique structural and electronic characteristics have revolutionized the field of nanotechnology and are widely used the field of transistors, drug delivery, and nanocomposities. For improved efficiency of these applications, the utilized tubes must of preeminent purity. Here, we report key parameters that are optimized to achieve their highest purity upto 98 wt%, and yield as high as 50 wt% by thermal and chemical oxidation. The as-produced SWCNT were heated in air at 470 degrees C, for 90 min, and later subjected to chemical oxidation. The chemical oxidation involved the treatment of thermally treated SWCNT with different concentrations of HCl (4N, 6N, 8N) and 30% H2O2, for different time periods (4 hr, 6 hr). This method does not cause damage to the walls of the tubes, observing no loss of nanotubes. The sheet resistance of as-produced and purified tubes was measured and the conductivity was calculated. PMID- 27398572 TI - Properties and Applications of Sodium (5-methyl-2-alkyl-1,3-dioxane-5-yl) Carboxylate Synthesized with Nanosolid Superacid. AB - A series of novel sodium (5-methyl-2-alkyl-1,3-dioxane-5-yl) carboxylate surfactants were synthesized using nanosolid superacid SO42-/Fe2O3as a catalyst and characterized by 1H NMR, IR and elemental analysis. The critical micelle concentration (CMC) of surfactants was determined and the results showed that the CMC values were less than 2.0 x 10-3 mol/L. Other relevant surface properties (Krafft point, emulsion stability, foam ability, degradability) were also evaluated. It was suggested that with respect to emulsion formation, foam stability and the range of application temperature, compared with traditional surfactants, the new surfactants could give better results and showed better properties when used as an emulsifier in emulsion polymerization. In addition, the surfactants were stable under neutral and alkaline conditions, and could form solid under acid condition. The solid will generate the original surfactants for reuse with alkali. Sodium (5-methyl-2-alkyl-1,3-dioxane-5-yl) carboxylate is likely to be a new type of 'environmentally friendly' surfactant. PMID- 27398573 TI - Antimicrobial Properties of Lysosomal Enzymes Immobilized on NH2Functionalized Silica-Encapsulated Magnetite Nanoparticles. AB - The immobilization efficiency, antimicrobial activity and recovery of lysosomal enzymes on NH2 functionalized magnetite nanoparticles have been studied under various conditions. The immobi- lization efficiency depends upon the ratio of the amount of enzyme and magnetite and it shows an increase with magnetite concentration which is due to the presence of amine group at the magnetite surface that leads to a strong attraction. The optimized reaction time to immobilize the lysosomal enzymes on magnetite was determined by using a rolling method. The immobilization efficiency increases with reaction time and reached a plateau after 5 minutes and then remained constant for 10 minutes. However, after 30 minutes the immobilization efficiency decreased to 85%, which is due to the weaker electrostatic interactions between magnetite and detached lysosomal enzymes. The recovery and stability of immobilized lysosomal enzymes has also been studied. The antimicrobial activity was almost 100% but it decreased upon reuse and no activity was observed after its reuse for seven times. The storage stability of lysosomal enzymes as an antimicrobial agent was about 88%, which decreased to 53% after one day and all activity of immobilized lysosomal enzymes was maintained after five days. Thus, the lysosomal enzymes immobilized on magnetite nanoparticles could potentially be used as antimicrobial agents to remove bacteria. PMID- 27398574 TI - Einstein's Photoemission from Quantum Confined Superlattices. AB - This paper is dedicated to the 83th Birthday of Late Professor B. R. Nag, D.Sc., formerly Head of the Departments of Radio Physics and Electronics and Electronic Science of the University of Calcutta, a firm believer of the concept of theoretical minimum of Landau and an internationally well known semiconductor physicist, to whom the second author remains ever grateful as a student and research worker from 1974-2004. In this paper, an attempt is made to study, the Einstein's photoemission (EP) from III-V, II-VI, IV-VI, HgTe/CdTe and strained layer quantum well heavily doped superlattices (QWHDSLs) with graded interfaces in the presence of quantizing magnetic field on the basis of newly formulated electron dispersion relations within the frame work of k . p formalism. The EP from III-V, II-VI, IV-VI, HgTe/CdTe and strained layer quantum wells of heavily doped effective mass superlattices respectively has been presented under magnetic quantization. Besides the said emissions, from the quantum dots of the aforementioned heavily doped SLs have further investigated for the purpose of comparison and complete investigation in the context of EP from quantum confined superlattices. Using appropriate SLs, it appears that the EP increases with increasing surface electron concentration and decreasing film thickness in spiky manners, which are the characteristic features of such quantized hetero structures. Under magnetic quantization, the EP oscillates with inverse quantizing magnetic field due to Shuvnikov-de Haas effect. The EP increases with increasing photo energy in a step-like manner and the numerical values of EP with all the physical variables are totally band structure dependent for all the cases. The most striking features are that the presence of poles in the dispersion relation of the materials in the absence of band tails create the complex energy spectra in the corresponding HD constituent materials of such quantum confined superlattices and effective electron mass exists within the band gap which is impossible without the concept of band tails. The well-known result of EP for bulk semiconductors having parabolic energy bands can be obtained as a special case of our generalized formulation and thus confirming the compatibility test. The content of this paper finds four important applications and we have suggested the methods of experimental determinations of important transport quantities in the field of quantum effect devices of nanoscience and nanotechnology. PMID- 27398575 TI - Sintering Behavior and Effect of Silver Nanowires on the Electrical Conductivity of Electrically Conductive Adhesives. AB - In this paper, two kinds of silver nanowires with a 160 nm average diameter ranging from 30 to 90 um length and a 450 nm average diameter up to 100 um length were successfully synthesized by a polyol process with FeCl3 and Na2S as reaction inhibitor, respectively. The experimental results indicate that the morphologies and sintering behaviors of both of silver nanowires are impacted by glutaric acid and sintering temperature. The isotropically conductive adhesives (ICAs) filled with micro-sized silver flakes and silver nanowires as hybrid fillers were fabricated and the electrical properties were investigated based on the fraction of the silver nanowires of the total of silver fillers and the curing temperature, etc. The in situ monitoring the variation in electrical resistance of the ICAs explores that silver nanowires have influence on the curing behavior of the ICAs. Silver nanowires synthesized with Na2S as reaction inhibitor and treated with glutaric acid can significantly improve the electrical conductivity of the ICAs in the case of the low loading of silver fillers in the appropriate proportion range of the weight ratio of micro-sized silver flakes and silver nanowires, primarily as a result of connecting effect. When the loading of silver fillers in the ICAs is high, the electrical conductivity is also enhanced slightly in the case of the proper fraction of silver nanowires of the total of silver fillers. The effect of the curing temperature on the electrical conductivity relates to the fraction of silver nanowires and the total loading of silver fillers. The electrical conductivity of the ICAs filled with micro-sized silver flakes and silver nanowires synthesized with FeCl3 as reaction inhibitor is greatly damaged, indicating that the size of silver nanowires also is one of main factor to impact the electrical conductivity of the ICAs doped with silver nanowires. The electrical property of the ICAs filled with micro-sized silver flakes and silver nanowires results mainly from the synergy of silver flakes and nanowires, forming the conductive pathways. PMID- 27398576 TI - Hybridization Between Natural Extract of Angelica gigas Nakai and Inorganic Nanomaterial of Layered Double Hydroxide via Reconstruction Reaction. AB - We have hybridized layered double hydroxide (LDH) with Angelica gigas Nakai root extract (AGNR) through reversible dehydration-rehydration reaction which is known as reconstruction. LDHs having well-ordered hydrotalcite-like crystal structure and average size 250 +/- 20 nm were prepared by hydrothermal method. The root of Angelica gigas Nakai, which has been utilized in the treatment of female disorders as herbal medicine, was treated with methanol to obtain extract. Pristine LDHs were calcined at 400 degrees C for 8 hours to obtain layered double oxide (LDO), which was further dispersed into extract solution with various AGNR/LDO weight ratios, 0.11, 0.21 and 0.43. The extract content in each hybrid increased in proportion to initial AGNR/LDO ratio, showing the highest content of ~12%. The zeta potential of LDH shifted from +44 mV to +20 mV upon hybridization with extract, which was attributed to the adsorption of negatively charged organic moieties in AGNR on LDH surface. The scanning electron microscopic (SEM) results exhibited that the random stacking of LDH nanolayers resulted in LDH-AGNR hybrid with house-of-cards structure, of which inter particle cavity serves nano-reservoir for natural extract. According to quantitative analyses, it was revealed that the content of active components in AGNR increased when they were hybridized with LDHs compared with those in AGNR alone. PMID- 27398577 TI - Elaboration, Structure and Luminescence of Sphere-Like CaF2:RE Sub-Microparticles by Ionic Liquids Based Hydrothermal Process. AB - A new and simple method for the synthesis of rare earth ion doped CaF2 (CaF2:RE3+) sub- microparticles is presented, using an ionic liquids based hydrothermal process. The structural properties of the CaF2 nanoparticles were investigated using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The CaF2 nanoparticles exhibited a sphere-like morphology with a diameter of about 150 nm. During the synthesis, the ionic liquid [bmim]BF4(1-butyl, 2-methylimidazolium tetrafluoroborate) acts as both a co-solvent and reactant. The crucial effect of EDTA-2Na (ethylene diamine tetra acetic acid disodium salt) on the formation of CaF2:RE sub-microparticles was explored and discussed. The strong green (513-569 nm) and strong red (636-685 nm) upconversion emissions of the CaF2:Er3+, Yb3+ nanoparticles (lambdaex = 980 nm) were also investigated. The luminescent properties of CaF2:Eu3+ and CaF2:Ce3+,Tb3+ were also evaluated. This work may represent a new step in synthesizing fluoride sub-nanocrystals using ionic liquids. PMID- 27398578 TI - Microwave Synthesis of Nanoparticulate SmFeO3 and Its Characterization. AB - Single phase perovskite SmFeO3 nanoparticles were synthesized using a simple microwave method using Fe(NO3)3. 9H2O and Sm(NO3)3 . 6H2O. The resulting samples were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area measurement, UV visible diffuse reflectance spectroscopy (DRS) and Fourier transform infrared spectroscopy (FTIR). XRD and SEM results demonstrate the successful synthesis of nanocrystalline SmFeO3 and show an average grain size of 50-60 nm. The single phase structure and optical properties of SmFeO3 were maintained after calcination at 1000 degrees C. The prepared nanocrystalline SmFeO3 displays excellent thermal stability and strong visible-light absorption, with an absorption onset of 540 nm or so. The photocatalytic experiment involving the decomposition of methyl orange under visible-light irradiation shows the high photocatalytic activity of the nanoparticles. PMID- 27398579 TI - Preparation and High Permeance of SiO2-Modified Substrate Supported ZSM-5 Membrane by Pre-Seeding and Secondary Nucleation. AB - SiO2-modified substrate supported compact ZSM-5 membranes with high permeance were prepared using the secondary nucleation method. The synthesis mixture had a molar composition of 10Na2O:84SiO2: 100NaCI:5TPABr:3500H2O. In order to obtain high permeance, a SiO2 meso- porous top layer was added to the macroporous substrate in this study. The SEM images of the seed layer indicate that about 400 500 nm round shaped seeds consisting of 60 nm zeolites fully covered the modifying substrate. The XRD patterns of the zeolite membranes show the purity of the ZSM-5 crystal phase, and reveal the formation of a random orientation on the SiO2-modified substrate. The SEM images of the zeolite membranes indicate that the membranes consist of highly intergrown crystals, with a maximum thickness of about 30 um. The results of gas permeability studies indicate that the SiO2 modified substrate supported ZSM-5 membranes show good permeance, with the maximum H2permeance achieved being 12.5 x 10-7 mol s-1 m-2 Pa-1. The maximum H2/N2 and H2/CO permselectivities were 4.01 and 4.37 respectively, which are higher than those of the corresponding Knudsen diffusion. The method used resulted in high permeance, while keeping the sustainable permselectivity, and is therefore desirable for practical applications. PMID- 27398580 TI - Gold and Hydroxyapatite Nano-Composite Scaffolds for Anterior Cruciate Ligament Reconstruction: In Vitro Characterization. AB - Current anterior cruciate ligament (ACL) graft replacement materials often fail due to the lack of biological integration. While many newly developed extracellular matrix based scaffolds show good biocompatibility they often do not entice cellular remodeling and the rebuilding of a functional ligament. We have proposed the conjugation of gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) to acellular tissue to enhance cell attachment and proliferation while maintaining an improved degradation resistance and open microstructure. We are the first to investigate the double conjugation of AuNP and nano-HAp onto decellularized tissue to improve the tissue remodeling response. Decellularized porcine diaphragm was crosslinked with two types of nano HAp and amine-functionalized AuNP with 1-ethyl-3-(3-dimethlaminopropyl) carbodiimide (EDC) crosslinker. Scaffolds were characterized using electron microscopy, differential scanning calorimetry, and fibroblast assays. Results demonstrated that scaffolds with nano-HAp have increased thermal stability at low levels of crosslinking. The open microstructure of the scaffold was not compromised allowing for cell migration while still providing increased degradation resistance. The addition of < 200 nm nano-HAp decreased cell viability compared to scaffolds without nanoparticles, but the addition of AuNP to scaffolds showed enhanced cell viability in the presence of < 200 nm nano-HAp. The addition of < 40 nm nano-HAp showed an increase in cell viability compared to scaffolds crosslinked without nanoparticles. It is concluded that attaching AuNP and < 40nm nano-HAp to extracellular matrices may improve overall properties. PMID- 27398581 TI - Hierarchical ZnO Superstructures: Nanoflake-Decorated Nanonail Arrays. AB - By using metallic Zn powders as zinc source, we synthesized unusual hierarchical ZnO superstructures, nanoflake-decorated nanonail arrays, on a large scale via a simple low-temperature thermal evaporation method. The hierarchical superstructures were characterized by using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, high resolution transmission electron microscopy as well as selected area electron diffraction. Studies found that both the ZnO nanonails and the decorated ZnO nanoflakes are single-crystals, with the preferred growth orientations along the (001) direction. The possible formation mechanism for the interesting hierarchical superstructures has been discussed. It was found that the deposition of indium films on a Si substrate and the heterogeneous nucleation of ZnO nanoflakes on the main ZnO nanonails play key roles in the fabrication of ZnO superstructures. Moreover, these special hierarchical superstructures showed much strong and complicated photoluminescent emissions in the visible region. PMID- 27398582 TI - Influence of Chemical Treatment on the Morphology and Functionalization of Carbon Nanotubes. AB - Multi-walled carbon nanotubes (MWCNTs) were functionalized by different oxidative treatments to insert polar groups on their surface. The treatments included sulfuric/nitric acid mixture, 6 M nitric acid solution, concentrated hydrochloric acid, sulfuric/potassium permanganate solution, and alkaline solution. The procedures succeeded in eliminating catalyst residues remaining from the MWCNT synthesis. Physical treatment by sonication was used to modify the intertubular distances and to reduce the average particle size. The materials obtained were characterized by X-ray diffraction and their morphology was studied by TEM. Particle size was analyzed by dynamic light scattering. FTIR spectroscopy was used to confirm the presence of functional groups and thermo-gravimetry (TGA) was employed to estimate the oxidation degree attained. The results confirmed polar group insertion on the surface of treated carbon nanotubes. Oxidation with 6 M nitric acid followed by sonication in xylene was found to be the most effective treatment. PMID- 27398583 TI - Graphene Oxide Based Fluorometric Detection of Hydrogen Peroxide in Milk. AB - We report a highly rapid, visual, precise, selective and sensitive analytical method for the determination of hydrogen peroxide (H2O2) in milk using Graphene oxide (GO) with 2',7'-dichlorfluorescein diacetate (DCFH-DA). A 1000 uL aliquots of 10-fold diluted samples (high and low-fat milk) directly onto the 100 uL of GO and 100 uL of 100 uM DCFH-DA produced green colour under Ultraviolet light at 365 nm. The analytical feature of our proposed method includes low detection limit (10 mmol mL-1) and satisfactory recovery values for samples. The presence of H202 in milk is a major concern because it constitutes a public health hazard. Many milk indursties are using H2O2 as a preservative, but if the concentration increases then it causes so many health problems such as neurodegenerative disorders, cancer and diabetes. Present methods show an easy way for detecting H2O2 generally require considerable time and laboratory facilities. The chemical tests have sufficient sensitivity to detect wide linear range of H2O2 concentration. PMID- 27398584 TI - Towards Intravenous Drug Delivery: Augmenting the Stability and Dispersity of Bis Demethoxy Curcumin Analog by Bottom-Up Strategy. AB - Intravenous route is the best strategy to accomplish fastest and highest delivery of drugs. Hydrophobic drugs like curcumin and its analog exhibit disadvantages like low bioavailability, poor absorption and rapid precipitation on intravenous delivery, all leading to its poor therapeutic value. These can be by-passed by enhancing the dispersity, stability and decreasing the size of the drug by nanotization. Thus, with an intention to deliver bis-demethoxy curcumin analog via intravenous route, we have studied the effect of DMSO, ethanol and acetone on the size, size distribution, stability and yield and identified the best solvent in terms of smallest size, narrow size distribution, more stability and high yield of nano bis-demethoxy curcumin analog (NBDMCA). NBDMCA prepared using DMSO showed the lowest mean particle size cum polydispersity index and highest zeta potential when compared to ethanol and acetone. Hence the DMSO based formulation can provide prolonged action and better efficacy at minimal doses. Thus, the DMSO based NBDMCA can emerge as an ideal therapeutic tool for human use. PMID- 27398585 TI - Enhanced Power Conversion Efficiency of Graphene/Silicon Heterojunction Solar Cells Through NiO Induced Doping. AB - We report a doping strategy, where nickel oxide (NiO) nanoparticle film coating is employed for graphene/Si heterojunction solar cells to improve the power conversion efficiency (PCE). NiO doping has been shown to improve the short circuit current (J(SC)) by 12%, open circuit voltage (V(OC)) by 25% and fill factor (FF) by 145% of the cells, in turn increasing the PCE from 1.37% to 4.91%. Furthermore, NiO doped graphene/Si solar cells don't show any significant performance degradation over 10 days revealing that NiO doping can be a promising approach for practical applications of graphene in solar cells. PMID- 27398586 TI - HCl-Retarded Gold Nanorod Growth for Aspect Ratio and Shape Tuning. AB - Traditionally, gold nanorods (GNRs) are mostly prepared via a seed-mediated growth approach, which usually produce an initial burst growth followed by slower kinetics and generate dogbone- shaped GNRs with relatively small aspect ratios (ARs). We demonstrate here that the growth of GNRs can be effectively retarded by addition of hydrochloric acid (HCl), leading to the formation of symmetric, long GNRs with high ARs. Furthermore, time-dependent kinetic analysis of GNR growth reveals two completely different growth modalities: in the absence of HCl, the GNR growth is rapid, reaching a concentration of 0.64 nM in 10 min. Its AR also rapidly reaches a maximum value of 4.1 at 2 min and then gradually decreases to 3.3 over 5 h. In sharp contrast, in the presence of HCI additive, the GNR growth happens very slowly, reaching a concentration of 0.33 nM at 7 h, and the AR also grows slowly to reach a maximum value of 5.3 at 3 h. These growth modalities endow different formation mechanisms of GNRs, which determine their aspect ratios and shape. PMID- 27398587 TI - A Facile Synthesis of Mesoporous Sulfonated Carbon and Its Structural Properties. AB - Mesoporous sulfonated carbons (SC) have been synthesized using tetraethyl orthosilicate (TEOS) as a silica source and sucrose as carbon source. The synthesized SC samples were carbonized in N2flow at various high temperatures and then passing high purity air at room temperature. In this study, we extended the idea to deposit more oxygen functional groups into the surface of SC being high micropores for the favorable adsorption applications. The resulting materials were characterized by using XRD, BET surface area, TPD, TEM, TGA and FTIR techniques. Mesoporous SC materials with controllable pore diameters are expected to be significant to future research concerning the improvement of catalysis, supercapacitors, fuel cells and adsorption. PMID- 27398588 TI - Synthesis and Characterization of Bi2Te3/Te Superlattice Nanowire Arrays. AB - Bi2Te3/Te superlattice nanowires were synthesized in anodic alumina membranes by annealing Bi-Te alloy nanowires. The morphologies and elements compositions of the superlattice and alloy nanowires were characterized using SEM and TEM, and the results confirmed the atomic ratio (Bi to Te) to be 2:3 and the formation of superlattice structure. PMID- 27398589 TI - Hybrid Gas Sensing and Transport Properties of Few-Walled CNTs Decorated with Discrete SnO2 Nanoparticles. AB - CVD grown, few walled carbon nanotubes (FWCNTs) were quasi decorated with SnO2nanoparticles (FWCNTs-SnO2) and its gas sensing properties were analyzed with ammonia and ethanol. At room temperature FWCNTs-SnO2show enhanced 'p type' gas sensing response than FWCNTs. Activation of SnO2at high temperatures led to systematic changes in the sensing behavior towards 'n type' response. Temperature dependent transport behavior was found to be a one dimensional variable range hopping mechanism (1 D-VRH) for the FWCNTs and a 3D-VRH mechanism for the FWCNTs SnO2. These temperature dependent gas transport and sensing properties elucidate the hybrid nature of the nanocomposite with novel characteristics. This also implies its importance as a potential gas sensor material. PMID- 27398590 TI - Non-Volatile Flash Memory Characteristics of Tetralayer Nickel-Germanide Nanocrystals Embedded Structure. AB - Formation of tetralayer memory structure having nickel-germanide nanocrystals using a Ge/Ni multilayers is proposed. X-ray diffraction study shows the NiGe (002) phase formation after proper annealing. Cross sectional HRTEM clearly shows the sharpness and the size (~4-6 nm) of the stacked nanocrystals embedded in the oxide matrix. A large anti-clockwise hysteresis memory win- dow of 13.4 Volt at +/- 15 Volt is observed for the optimized samples. This large memory window indicates for the MLC applications. Frequency independent C-V curve confirms about the charge storage in the nanocrystals. A good charge retention and endurance characteristics are exhibited upto 125 degrees C for the nonvolatile memory application. PMID- 27398591 TI - One-Step Hydrothermal Synthesis of Butanetetracarboxylic Acid-Coated NaYF4:Yb3+, Er3+ Upconversion Phosphors with Enhancement Upconversion Luminescence. AB - Butanetetracarboxylic acid (BTCA)/NaYF4:Yb3+, Er3+ upconversion phosphors have been successfully synthesized by a one-step hydrothermal method. The SEM and XRD results show the as-prepared phosphors exhibit main hexagonal lattice structures and uniform morphologies. FT-IR spectra confirm that the surface of as-prepared phosphors is inherently modified with the carboxyl groups. Under the excitation of 980 nm, it has been observed that BTCA/NaYF4:Yb3+, Er3+ upconversion phosphors have a higher upconversion luminescence efficiency than that coated with citrate, ethylenediamine tetraacetic acid (EDTA), or polyacrylic acid (PAA). These results indicate that the BTCA/NaYF4:Yb3+, Er3+ phosphors may have superior optical properties, and thus have great potential for biological applications. PMID- 27398592 TI - Nanoporous Carbon Monoliths with Tunable Thermal Insulation and Mechanical Properties. AB - In this work, nanoscale porous carbon monoliths, with excellent compressive strength and thermal insulation, were obtained with a simple method of carbonizing cured phenol-formaldehyde resin/poly(methyl methacrylate) blends. Apparent density, pore size and morphology of the carbon monoliths were tailored by changing the composition, curing process and carbonization temperature. The continuous nanopores played a key role in enhancing mechanical and thermal performance of the carbon materials. When PMMA concentration was 25%, apparent density and thermal conductivity of the nanoporous carbonaceous monoliths were obtained as low as 1.07 g . cm-3 and 0.42 W/(m . K), decreasing by 29.4% and 35.4% than that of carbonaceous monoliths obtained from pure PF; while compressive strength of the nanoporous carbonaceous monoliths was as high as 34 MPa, which was improved over five times than that of pure PF carbon monoliths. PMID- 27398593 TI - Einstein's 1D Photo Emission and the Von Klitzing Constant. AB - An attempt is made to present a very easy integration which generates Von Klitzing constant in one hand and Einstein's 1D photo current from quantum wires having arbitrary band structures under the practical conditions of extreme degeneracy and quantum limits on the other hand, the two radically different concepts, depending on the selection of the values of the upper and lower limits of the integral. PMID- 27398594 TI - Nanotechnology Applied to Bio-Encapsulation of Pesticides. AB - In recent years, many efforts have been made towards the application of nanotechnology in sustainable food production. In this context, the bio encapsulation process has taken prominence in particular as an ecofriendly method for pest control while reducing the pesticide load in the environment considerably. By taking into consideration, here we are presenting an overview regarding the prospects for the development of nanoencapsulated pesticides in sustainable agriculture and highlight some challenges to be addressed in order to develop efficient nano-carrier systems that may arise as an alternative for conventional pesticide application. However, much research has to be done in this area in order to develop safe and promising pesticide delivery systems for increasing global food production by enhancing the selectivity, specificity and longevity of the encapsulated pesticides while reducing the negative environmental impacts to ecosystem and human beings. PMID- 27398595 TI - Inter-Rater Agreement in the Clinical Diagnosis of Cognitive Status: Data from the Neurological Disorders in Central Spain 2 Pilot Study. AB - BACKGROUND: To assess the diagnostic agreement of cognitive status (dementia, mild cognitive impairment (MCI), normal cognition) among neurologists in the field of neurological disorders in Central Spain 2 study. METHODS: Full medical histories of 30 individuals were provided to 27 neurologists: 9 seniors, 10 juniors and 8 residents. For each case, we were asked to assign a diagnosis of dementia, MCI or normal cognition using the National Institute on Aging Alzheimer's Association workgroup (NIA-AA) core clinical criteria for all-cause dementia, Winblad et al. criteria for MCI, and analyze intensity and etiology if dementia was diagnosed. Inter-rater agreement was assessed both with percent concordance and non-weighted kappa statistics. RESULTS: Overall inter-rater agreement on cognitive status was kappa = 0.76 (95% CI 0.65-0.86), being slightly higher among junior neurologists (kappa = 0.85, 95% CI 0.73-0.95) than among seniors (kappa = 0.71, 95% CI 0.59-0.83) and residents (kappa = 0.69, 95% CI 0.54 0.81) but without statistical significance among groups. Dementia severity showed an overall kappa of 0.34, 0.44 and 0.64 for mild, moderate and severe dementia respectively. CONCLUSIONS: Substantial agreement was demonstrated for the diagnosis of cognitive status (dementia, MCI and normal cognition) among neurologists of different levels of experience in a population-based epidemiological study using NIA-AA and Winblad et al. CRITERIA: The agreement rate was lower in the diagnosis of dementia severity. PMID- 27398597 TI - Contact Radius and the Insulator-Metal Transition in Films Comprised of Touching Semiconductor Nanocrystals. AB - Nanocrystal assemblies are being explored for a number of optoelectronic applications such as transparent conductors, photovoltaic solar cells, and electrochromic windows. Majority carrier transport is important for these applications, yet it remains relatively poorly understood in films comprised of touching nanocrystals. Specifically, the underlying structural parameters expected to determine the transport mechanism have not been fully elucidated. In this report, we demonstrate experimentally that the contact radius, between touching heavily doped ZnO nanocrystals, controls the electron transport mechanism. Spherical nanocrystals are considered, which are connected by a circular area. The radius of this circular area is the contact radius. For nanocrystals that have local majority carrier concentration above the Mott transition, there is a critical contact radius. If the contact radius between nanocrystals is less than the critical value, then the transport mechanism is variable range hopping. If the contact radius is greater than the critical value, the films display behavior consistent with metallic electron transport. PMID- 27398596 TI - Transcriptome Analysis of Capsicum Chlorosis Virus-Induced Hypersensitive Resistance Response in Bell Capsicum. AB - BACKGROUND: Capsicum chlorosis virus (CaCV) is an emerging pathogen of capsicum, tomato and peanut crops in Australia and South-East Asia. Commercial capsicum cultivars with CaCV resistance are not yet available, but CaCV resistance identified in Capsicum chinense is being introgressed into commercial Bell capsicum. However, our knowledge of the molecular mechanisms leading to the resistance response to CaCV infection is limited. Therefore, transcriptome and expression profiling data provide an important resource to better understand CaCV resistance mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We assembled capsicum transcriptomes and analysed gene expression using Illumina HiSeq platform combined with a tag-based digital gene expression system. Total RNA extracted from CaCV/mock inoculated CaCV resistant (R) and susceptible (S) capsicum at the time point when R line showed a strong hypersensitive response to CaCV infection was used in transcriptome assembly. Gene expression profiles of R and S capsicum in CaCV- and buffer-inoculated conditions were compared. None of the genes were differentially expressed (DE) between R and S cultivars when mock-inoculated, while 2484 genes were DE when inoculated with CaCV. Functional classification revealed that the most highly up-regulated DE genes in R capsicum included pathogenesis-related genes, cell death-associated genes, genes associated with hormone-mediated signalling pathways and genes encoding enzymes involved in synthesis of defense-related secondary metabolites. We selected 15 genes to confirm DE expression levels by real-time quantitative PCR. CONCLUSION/SIGNIFICANCE: DE transcript profiling data provided comprehensive gene expression information to gain an understanding of the underlying CaCV resistance mechanisms. Further, we identified candidate CaCV resistance genes in the CaCV resistant C. annuum x C. chinense breeding line. This knowledge will be useful in future for fine mapping of the CaCV resistance locus and potential genetic engineering of resistance into CaCV-susceptible crops. PMID- 27398599 TI - Anti-Obesity Effects of Spiramycin In Vitro and In Vivo. AB - The effects of spiramycin on adipogenesis and high fat diet (HFD)-induced obesity were investigated. Potential mechanisms contributing to these effects were elucidated. The inhibitory effect of spiramycin on adipocyte differentiation was assessed using 3T3-L1 preadipocyte cells, in which several parameters involved in AMPK signal pathways and lipid metabolism were examined. To further investigate the pharmacological effects of spiramycin in vivo, we examined several obesity related parameters in HFD-induced obese mice. Spiramycin significantly inhibited preadipocyte differentiation by attenuating intracellular lipid accumulation. Spiramycin also reduced the expression of adipogenic master regulators (PPARgamma, C/EBPalpha, and SREBP1c) and their downstream target genes (FAS, aP2, and GLUT4) in 3T3-L1 cells. In addition, AMPK phosphorylation was increased by spiramycin treatment in 3T3-L1 cells during early differentiation. Notably, HFD induced obese mice administered spiramycin showed substantial decreases in body weight gain, serum leptin levels, adipose tissue mass, and hepatic lipid accumulation. Moreover, the decreased levels of GPT and GOT in the serum indicated that spiramycin attenuated hepatic injury caused by HFD. Taken together, these results demonstrate for the first time that spiramycin effectively attenuates HFD-induced obesity and hepatic steatosis by inhibiting adipogenesis. PMID- 27398601 TI - Recurrent Vascular Access Dysfunction as a Novel Marker of Cardiovascular Outcome and Mortality in Hemodialysis Patients. AB - BACKGROUND: Vascular access (VA) is essential for hemodialysis (HD) patients, and its dysfunction is a major complication. However, little is known about outcomes in patients with recurrent VA dysfunction. We explored the influence of recurrent VA dysfunction on cardiovascular (CV) events, death and VA abandonment. METHODS: This is a single-center, retrospective study conducted in patients who underwent VA surgery between 2009 and 2014. VA dysfunction was defined as VA stenosis or thrombosis requiring intervention after the first successful cannulation. Patients with >=2 interventions within 180 days were categorized as having recurrent VA dysfunction. Outcomes were analyzed using Cox proportional hazards model before and after propensity score matching. RESULTS: Of 766 patients (ages 59.6 +/- 14.3 years, 59.7% male), 10.1% were in the recurrent VA dysfunction group. Most baseline parameters after matching were similar between the recurrent and non-recurrent groups. A total of 213 propensity score-matched patients were followed for 28.7 +/- 15.8 months, during which 46 (21.6%), 30 (14.1%) and 14 (6.6%) patients had de novo CV outcomes, died and abandoned VA, respectively. Recurrent VA dysfunction after adjustment remained an independent risk factor for CV events (adjusted hazards ratio (aHR), 2.71; 95% CI 1.48-4.98; p = 0.001). Moreover, recurrent VA dysfunction predicted composite all-cause mortality (ACM)/CV events (aHR 1.99; 95% CI 1.21-3.28; p = 0.007). CONCLUSIONS: Recurrent VA dysfunction was a novel independent risk factor for CV and composite ACM/CV events in HD patients, but not for VA abandonment. Patients with recurrent vascular dysfunction should be carefully monitored not only for VA patency but also for CV events. PMID- 27398600 TI - Dynamic Reweighting of Auditory Modulation Filters. AB - Sound waveforms convey information largely via amplitude modulations (AM). A large body of experimental evidence has provided support for a modulation (bandpass) filterbank. Details of this model have varied over time partly reflecting different experimental conditions and diverse datasets from distinct task strategies, contributing uncertainty to the bandwidth measurements and leaving important issues unresolved. We adopt here a solely data-driven measurement approach in which we first demonstrate how different models can be subsumed within a common 'cascade' framework, and then proceed to characterize the cascade via system identification analysis using a single stimulus/task specification and hence stable task rules largely unconstrained by any model or parameters. Observers were required to detect a brief change in level superimposed onto random level changes that served as AM noise; the relationship between trial-by-trial noisy fluctuations and corresponding human responses enables targeted identification of distinct cascade elements. The resulting measurements exhibit a dynamic complex picture in which human perception of auditory modulations appears adaptive in nature, evolving from an initial lowpass to bandpass modes (with broad tuning, Q~1) following repeated stimulus exposure. PMID- 27398602 TI - Nephroprotective Effect of the Leaves of Aloe barbadensis (Aloe Vera) against Toxicity Induced by Diclofenac Sodium in Albino Rabbits. AB - Background: The present study was designed to evaluate the nephroprotective effect of the leaves of Aloe barbadensis against toxicity induced by diclofenac sodium in albino rabbits. Subjects and Method: Thirty-six healthy albino rabbits were randomly divided into six groups each with six animals. Group 1 served as the untreated control, group 2 was treated only with diclofenac sodium, group 3 with the nephroprotective drug silymarin and groups 4, 5, and 6 were treated with different doses of Aloe barbadensis,ie 200 mg/kg, 400 mg/kg and 600 mg/kg, respectively after being treated with diclofenac sodium. Blood samples were collected after every five days up to fifteen days. Haematological and histopathological parameters were determined by using diagnostic kits. Results: Results of haematological studies showed that use of the powder of Aloe barbadensis normalized the level of different factors eg, white blood cells (WBCs), red blood cells (RBCs), platelet count, packed cell volume (PCV), mean cell volume (MCV) and haemoglobin (Hb) values. Histopathological studies showed that Aloe barbadensis ameliorated pyknotic nuclei in the renal epithelial cells and reduced oxidative stress by increasing the level of catalase and decreasing malondialdehyde (MDA) level. Conclusion: These results have shown that Aloe barbadensis can normalize oxidative stress and can be used as an effective nephroprotective agent against drug-induced nephrotoxicity. PMID- 27398605 TI - MeOTf- and TBD-Mediated Carbonylation of ortho-Arylanilines with CO2 Leading to Phenanthridinones. AB - Carbonylation of o-arylanilines utilizing CO2 as a carbonyl source for the synthesis of important phenanthridinones with a free (NH)-lactam motif has been described under metal-free condition. A range of o-arylanilines were transformed to the corresponding phenanthridinones in high yields. PMID- 27398608 TI - Response to the comment on ''Relationship between the IL12B (rs3212227) gene polymorphism and susceptibility to multiple autoimmune diseases: A meta analysis''. PMID- 27398609 TI - Sliding-Ring Catenanes. AB - Template-directed protocols provide a routine approach to the synthesis of mechanically interlocked molecules (MIMs), in which the mechanical bonds are stabilized by a wide variety of weak interactions. In this Article, we describe a strategy for the preparation of neutral [2]catenanes with sliding interlocked electron-rich rings, starting from two degenerate donor-acceptor [2]catenanes, consisting of a tetracationic cyclobis(paraquat-p-phenylene) cyclophane (CBPQT(4+)) and crown ethers containing either (i) hydroquinone (HQ) or (ii) 1,5 dioxynaphthalene (DNP) recognition units and carrying out four-electron reductions of the cyclophane components to their neutral forms. The donor acceptor interactions between the CBPQT(4+) ring and both HQ and DNP units present in the crown ethers that stabilize the [2]catenanes are weakened upon reduction of the cyclophane components to their radical cationic states and are all but absent in their fully reduced states. Characterization in solution performed by UV-vis, EPR, and NMR spectroscopic probes reveals that changes in the redox properties of the [2]catenanes result in a substantial decrease of the energy barriers for the circumrotation and pirouetting motions of the interlocked rings, which glide freely through one another in the neutral states. The solid state structures of the fully reduced catenanes reveal profound changes in the relative dispositions of the interlocked rings, with the glycol chains of the crown ethers residing in the cavities of the neutral CBPQT(0) rings. Quantum mechanical investigations of the energy levels associated with the four different oxidation states of the catenanes support this interpretation. Catenanes and rotaxanes with sliding rings are expected to display unique properties. PMID- 27398610 TI - Morphology Tuning of Electrospun Liquid Crystal/Polymer Fibers. AB - This paper elucidates the means to control precisely the morphology of electrospun liquid crystal/polymer fibers formed by phase separation. The relative humidity, solution parameters (concentration, solvent), and the process parameter (feed rate) were varied systematically. We show that the morphology of the phase-separated liquid crystal can be continuously tuned from capsules to uniform fibers with systematic formation of beads-on-a-string structured fibers in the intermediate ranges. In all cases, the polymer forms a sheath around a liquid-crystal (LC) core. The width of the polymer sheath and the diameter of the LC core increase with increasing feed rates. This is similar to the results obtained by coaxial electrospinning. Because these fibers retain the responsive properties of liquid crystals and because of their large surface area, they have potential applications as thermo-, chemo-, and biosensors. Because the size and shape of the liquid-crystal domains will have a profound effect on the performance of the fibers, our ability to precisely control morphology will be crucial in developing these applications. PMID- 27398611 TI - Mechanistic Photochemistry of Methyl-4-hydroxycinnamate Chromophore and Its One Water Complexes: Insights from MS-CASPT2 Study. AB - Herein we computationally studied the excited-state properties and decay dynamics of methyl-4-hydroxycinnamate (OMpCA) in the lowest three electronic states, that is, (1)pipi*, (1)npi*, and S0 using combined MS-CASPT2 and CASSCF electronic structure methods. We found that one-water hydration can significantly stabilize and destabilize the vertical excitation energies of the spectroscopically bright (1)pipi* and dark (1)npi* excited singlet states, respectively; in contrast, it has a much smaller effect on the (1)pipi* and (1)npi* adiabatic excitation energies. Mechanistically, we located two (1)pipi* excited-state relaxation channels. One is the internal conversion to the dark (1)npi* state, and the other is the (1)pipi* photoisomerization that eventually leads the system to a (1)pipi*/S0 conical intersection region, near which the radiationless internal conversion to the S0 state occurs. These two (1)pipi* relaxation pathways play distinct roles in OMpCA and its two one-water complexes (OMpCA-W1 and OMpCA-W2). In OMpCA, the predominant (1)pipi* decay route is the state-switching to the dark (1)npi* state, while in one-water complexes, the importance of the (1)pipi* photoisomerization is significantly enhanced because the internal conversion to the (1)npi* state is heavily suppressed due to the one-water hydration. PMID- 27398612 TI - Eupatorium lindleyanum DC. flavonoids fraction attenuates lipopolysaccharide induced acute lung injury in mice. AB - Eupatorium lindleyanum DC., "Ye-Ma-Zhui" called by local residents in China, showed anti-inflammatory activity and is used to treat tracheitis. We had isolated and identified the flavonoids, diterpenoids and sesquiterpenes compounds from the herb. In the present study, we evaluated the protective effects of the flavonoids fraction of E. lindleyanum (EUP-FLA) on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and the possible underlying mechanisms of action. EUP-FLA could significantly decrease lung wet-to-dry weight (W/D) ratio, nitric oxide (NO) and protein concentration in BALF, lower myeloperoxidase (MPO) activity, increase superoxide dismutase (SOD) activity and down-regulate the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta). Additionally, EUP-FLA attenuated lung histopathological changes and significantly reduced complement deposition with decreasing the levels of Complement 3 (C3) and Complement 3c (C3c) in serum. These results demonstrated that EUP-FLA may attenuate LPS-induced ALI via reducing productions of pro-inflammatory mediators, decreasing the level of complement and affecting the NO, SOD and MPO activity. PMID- 27398613 TI - Impact of MAPK and PI3K/AKT signaling pathways on Malabaricone-A induced cytotoxicity in U937, a histiocytic lymphoma cell line. AB - Intrinsically cancer cells have higher basal levels of reactive oxygen species (ROS), which when augmented by pro-oxidants such as Malabaricone-A (MAL-A) triggers apoptotic cell death, secondary to 'turning on' of the apoptosis related cell signaling pathways. The effects of MAL-A upon key inflammation related signaling molecules were evaluated by western blotting in U937, a histiocytic lymphoma derived cell line. The impact of inhibitors of the pro-apoptotic MAPK and anti-apoptotic PI3K/AKT signaling pathways upon MAL-A induced cytotoxicity and generation of ROS was evaluated by a cell viability assay and flow cytometry respectively in two hematopoietic cell lines, U937 and MOLT3. MAL-A enhanced phosphorylation of the components of the pro-apoptotic pathway, namely ASK1, p38 and JNK. Alongside, MAL-A decreased the phosphorylation of AKT and mTOR. The cytotoxicity of MAL-A was attenuated by inhibitors of p38 and JNK, whereas its cytotoxic potential was enhanced in the presence of a PI3K/AKT inhibitor. Similarly, MAL-A mediated generation of ROS was decreased by inhibitors of p38MAPK and JNK, whereas the PI3K/AKT inhibitor potentiated its generation of ROS. Taken together, MAL-A mediated its cytotoxicity by enhanced generation of ROS via modulation of the apoptosis related cellular signaling pathways and tilting the balance towards a pro-apoptotic scenario. This was achieved via an up regulation of MAPK (p38 and JNK) along with down-regulation of the PI3K/AKT/mTOR pathway indicating that manipulation of these pathways by compounds such as MAL-A are promising therapeutic targets, worthy of future pharmacological consideration. PMID- 27398614 TI - Embryonic stem cells: a novel paradigm to study proteostasis? AB - Embryonic stem cells (ESCs) exhibit a striking ability to replicate continuously in the absence of senescence. Despite the knowledge gained into ESC biology and cell reprogramming, the mechanisms that regulate their pluripotency, self renewal, and differentiation remain largely unknown. Recently, cumulative evidence has highlighted the importance of protein homeostasis, or proteostasis, in the maintenance of ESC function. These findings indicate that ESCs exhibit intrinsic differences in the regulation and activity of key nodes of the proteostasis network such as global protein synthesis, folding, and degradation rates. Here, we review new insights into proteostasis of ESCs and the questions raised by these findings. In addition, we discuss the potential of these discoveries to be applied into aging and cancer research. PMID- 27398615 TI - Physiology: Pancreatic beta-cell heterogeneity revisited. PMID- 27398616 TI - Engineering and mapping nanocavity emission via precision placement of DNA origami. AB - Many hybrid devices integrate functional molecular or nanoparticle components with microstructures, as exemplified by the nanophotonic devices that couple emitters to optical resonators for potential use in single-molecule detection, precision magnetometry low threshold lasing and quantum information processing. These systems also illustrate a common difficulty for hybrid devices: although many proof-of-principle devices exist, practical applications face the challenge of how to incorporate large numbers of chemically diverse functional components into microfabricated resonators at precise locations. Here we show that the directed self-assembly of DNA origami onto lithographically patterned binding sites allows reliable and controllable coupling of molecular emitters to photonic crystal cavities (PCCs). The precision of this method is sufficient to enable us to visualize the local density of states within PCCs by simple wide-field microscopy and to resolve the antinodes of the cavity mode at a resolution of about one-tenth of a wavelength. By simply changing the number of binding sites, we program the delivery of up to seven DNA origami onto distinct antinodes within a single cavity and thereby digitally vary the intensity of the cavity emission. To demonstrate the scalability of our technique, we fabricate 65,536 independently programmed PCCs on a single chip. These features, in combination with the widely used modularity of DNA origami, suggest that our method is well suited for the rapid prototyping of a broad array of hybrid nanophotonic devices. PMID- 27398617 TI - Rapid signalling in distinct dopaminergic axons during locomotion and reward. AB - Dopaminergic projection axons from the midbrain to the striatum are crucial for motor control, as their degeneration in Parkinson disease results in profound movement deficits. Paradoxically, most recording methods report rapid phasic dopamine signalling (~100-ms bursts) in response to unpredicted rewards, with little evidence for movement-related signalling. The leading model posits that phasic signalling in striatum-targeting dopamine neurons drives reward-based learning, whereas slow variations in firing (tens of seconds to minutes) in these same neurons bias animals towards or away from movement. However, current methods have provided little evidence to support or refute this model. Here, using new optical recording methods, we report the discovery of rapid phasic signalling in striatum-targeting dopaminergic axons that is associated with, and capable of triggering, locomotion in mice. Axons expressing these signals were largely distinct from those that responded to unexpected rewards. These results suggest that dopaminergic neuromodulation can differentially impact motor control and reward learning with sub-second precision, and indicate that both precise signal timing and neuronal subtype are important parameters to consider in the treatment of dopamine-related disorders. PMID- 27398618 TI - Diabetes: Still a geneticist's nightmare. PMID- 27398619 TI - Evidence for climate change in the satellite cloud record. AB - Clouds substantially affect Earth's energy budget by reflecting solar radiation back to space and by restricting emission of thermal radiation to space. They are perhaps the largest uncertainty in our understanding of climate change, owing to disagreement among climate models and observational datasets over what cloud changes have occurred during recent decades and will occur in response to global warming. This is because observational systems originally designed for monitoring weather have lacked sufficient stability to detect cloud changes reliably over decades unless they have been corrected to remove artefacts. Here we show that several independent, empirically corrected satellite records exhibit large-scale patterns of cloud change between the 1980s and the 2000s that are similar to those produced by model simulations of climate with recent historical external radiative forcing. Observed and simulated cloud change patterns are consistent with poleward retreat of mid-latitude storm tracks, expansion of subtropical dry zones, and increasing height of the highest cloud tops at all latitudes. The primary drivers of these cloud changes appear to be increasing greenhouse gas concentrations and a recovery from volcanic radiative cooling. These results indicate that the cloud changes most consistently predicted by global climate models are currently occurring in nature. PMID- 27398620 TI - Identification of proliferative and mature beta-cells in the islets of Langerhans. AB - Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of beta-cells. Pancreatic beta-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential; understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature beta-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs. We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger beta-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for beta-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional beta cell heterogeneity and induce beta-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional beta-cell mass in diabetic patients. PMID- 27398622 TI - Spinal sagittal balance status affects postoperative actual falls and quality of life after decompression and fusion in-situ surgery in patients with lumbar spinal stenosis. AB - OBJECTIVES: It has been reported that good spinal sagittal alignment reduces the risk of fall and positive sagittal balance is the radiographic parameter that is most highly correlated with adverse health outcomes. However, no reports have demonstrated a change in risk of falling in patients with lumbar spinal stenosis (LSS) according to sagittal balance status. PATIENTS AND METHODS: From September 2013 to October 2014, 141 patients who underwent lumbar spine surgery, including decompression and fusion in-situ for LSS, were enrolled in this study. Based on sagittal balance status, patients were divided into sagittal balance (SB) and sagittal imbalance (SI) groups. Four functional mobility tests were used to evaluate the risk of falling, and a fall diary, Oswestry disability index (ODI), and the Euro-QoL 5D(EQ-5D) visual analogue scale (VAS) were utilized to assess clinical improvement. RESULTS: The mean patient age was 70.1 years in the SB group (N=46) and 70.9 years in the SI group (N=95) (not significant). The mean C7PL was 7.9mm in the SB group and 66.1mm in the SI group preoperatively (p<0.05). Among the four functional tests, only postoperative SMT and STS improved significantly in the SB group (p<0.05). Patients in the SI group showed significantly improved scores for all four functional tests during postoperative follow-up (p<0.05), but their performance was still worse than patients in the SB group. Average number of falls per individual during the follow-up period was 1.1+/-2.5 in the SB group and 1.9+/-3.2 in the SI group (p<0.05). There was a significant difference in the distribution of non-fallers and fallers (single and multiple fallers) between the two groups postoperatively(p<0.05). ODI and the EQ 5D VAS showed greater improvement in the SB group than the SI group. Multiple regression analysis revealed that sagittal balance during follow-up significantly affected ODI, EQ-VAS, functional mobility tests. (p<0.05). CONCLUSION: Therefore, when fusion surgery is planned in patients with LSS, careful consideration of sagittal balance status might be important to attain better surgical and functional outcomes and decrease the incidence of actual falls after surgical treatment. PMID- 27398623 TI - Focal epileptic seizures, electroencephalography and outcome of sepsis associated encephalopathy-A pilot study. AB - OBJECTIVES: Sepsis associated encephalopathy (SAE) represents a diffuse and/or multifactorial cerebral dysfunction during response to systemic infection. Study aim was to compare clinical and electroencephalogram (EEG) characteristics and intrahospital survival rate among SAE patients. PATIENTS AND METHODS: A prospective study, during 42 months' period, included 39 SAE patients assigned in two groups according the outcome (survival: 19, and death: 20 patients). All the patients' features were registered: demography, neurological status, infection type, seizure appearance, brain computerized tomography (CT), EEG, EEG reactivity, Glasgow Coma Score (GCS) and Acute Physiology and Chronic Health Evaluation II (APACHE II) Score. The analysis included EEGs obtained during patients' consciousness change (improvement or deterioration) and the level of consciousness during and at the end of hospitalization. RESULTS: SAE was detected in 29.5% of patients with encephalopathy (2.8% of all patients hospitalized). Patients with lethal outcome were more likely to be female (p=0.0011), to have focal seizures (p=0.034), lower values of GCS during hospitalization (p<0.05) and longer lasting nosocomial infections (p=0.029). At the time of clinical exacerbation, patients were more likely to have suppression on EEG and less likely theta activity. Delta waves, TW waves and suppression of EEG activity were the most common findings 24h prior to death (p=0.0004). The lack of EEG reactivity was associated with death (p=0.00043). CONCLUSION: Presence of focal seizures, EEG suppression at the time of exacerbation in SAE elderly patients, particularly women, with longer infection duration and lower values of GCS, is associated with intrahospital death. PMID- 27398624 TI - A comparison of the diagnostic value of 2D strain stress echocardiography, myocardial perfusion scintigraphy, and Duke treadmill score in patients suspected of coronary artery disease. AB - BACKGROUND: Preinvasive risk stratification is recommended in patients suspected of coronary artery disease (CAD). Stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), and exercise test are the dominant methods of choice. Vasodilator SE is fast and induces only minor increase in heart rate. The diagnostic value of the absolute stress-rest difference in endocardial global longitudinal strain (DeltaeGLS) and wall motion (DeltaWMI) from adenosine SE was compared to summed stress score (SSS) from MPS and Duke treadmill score (DTS) from exercise test, using quantitative invasive coronary angiography (ICA) as the reference. METHODS AND RESULTS: A total of 128 patients (69% male, 62.7 (8.8) years) underwent adenosine SE, MPS, exercise test, and ICA. Forty-five patients (35%) had CAD. All stress outcomes differed significantly (P<.001) between patients with and without CAD: DeltaeGLS: -1.3 (3.6)% vs -5.0 (3.3)%; WMI: 1.20 (0.34) vs 1.06 (0.13); SSS: 12.5 (8.2) vs 1.7 (3.6); and DTS: -3.4 (9.0) vs 3.9 (5.5). The cutoff values yielding the best sensitivity/specificity/accuracy were as follows: DeltaeGLS: -2.3% or DeltaWMI: 0 (69%/84%/79%), SSS: 4 (82%/94%/90%), and DTS: 1 (73%/78%/77%). The sensitivity of DeltaeGLS + DeltaWMI was similar to SSS (P=.11) and DTS (P=.59). The specificity of DeltaeGLS + DeltaWMI was inferior to SSS (P=.03) and similar to DTS (P=.28). CONCLUSION: Alterations in eGLS and wall motion during adenosine SE were closely associated with the presence of CAD and the combined sensitivity similar to that of MPS. If nuclear medical facilities are unavailable or radiation issues important, vasodilator DeltaeGLS could be an acceptable alternative for patients unable to exercise. PMID- 27398625 TI - Role of regional aortic wall properties in the pathogenesis of thoracic aortic dissection. AB - OBJECTIVES: The mechanisms of the location and extension of acute aortic dissection (AD) are only poorly understood. The aim of this study was to compare the cohesion of the non-coronary aortic sinus (NAS) and the ascending aortic wall (AA) using the Dissectometer - a new device for analyses of the mechanical properties of the aorta. DESIGN: The properties of the aortic wall were analyzed with the "Dissectometer" (parameters P7, P8 and P9) in adult patients undergoing aortic root (AR) replacement in two different segments: NAS and AA. The aortic wall thickness (AWT) was measured with a micrometer. RESULTS: Thirty-three adult patients (mean age 65 +/- 14 years, 80% male) were included in this study. The aortic wall of the NAS was significantly thinner than that of the AA (1.9 +/- 0.4 vs. 2.3 +/- 0.4, p < 0.01). In contrast, mechanical stability assessed by cohesion testing was diminished in AA samples compared to NAS samples (P7: 86.0 +/- 55.0 vs. 152.3 +/- 89.2, p < 0.01; P8: 2.5 +/- 1.3 vs. 6.0 +/- 3.1, p < 0.01; P9: 3.6 +/- 1.4 vs. 7.8 +/- 3.2, p < 0.01). CONCLUSIONS: This study shows that the wall of the AR is characterized by a thin but stable wall, whereas AA was found to be weaker despite its greater thickness. This difference might be involved in the development and spreading of aortic dissections. PMID- 27398626 TI - Vorapaxar: emerging evidence and clinical questions in a new era of PAR-1 inhibition. AB - Despite the use of therapies recommended in practice guidelines for secondary prevention in patients with atherosclerotic coronary artery disease, the residual risk for cardiovascular events remains high. Some of the residual risk is believed to result from incomplete platelet inhibition with current therapy. Vorapaxar is a first-in-class, novel antiplatelet agent that acts by antagonizing the PAR-1 receptor, inhibiting thrombin-mediated platelet activation. Vorapaxar was recently approved by the Food and Drug Administration for secondary prevention of cardiovascular events in patients with a history of myocardial infarction or peripheral artery disease who do not have a history of transient ischemic attack or stroke. We review the data from two key phase III cardiovascular outcome trials with vorapaxar: TRACER and TRA 2P-TIMI 50. We will focus on identifying the key patient populations that should be identified for treatment, highlight practical clinical issues when prescribing vorapaxar, and review unanswered questions. Vorapaxar should be considered in patients at high risk for recurrent ischemic events and low risk of bleeding. PMID- 27398628 TI - The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity. AB - The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion. PMID- 27398627 TI - Translational Advances in the Field of Pulmonary Hypertension Molecular Medicine of Pulmonary Arterial Hypertension. From Population Genetics to Precision Medicine and Gene Editing. PMID- 27398629 TI - In quest of cathode materials for Ca ion batteries: the CaMO3 perovskites (M = Mo, Cr, Mn, Fe, Co, and Ni). AB - Basic electrochemical characteristics of CaMO3 perovskites (M = Mo, Cr, Mn, Fe, Co, and Ni) as cathode materials for Ca ion batteries are investigated using first principles calculations at the Density Functional Theory level (DFT). Calculations have been performed within the Generalized Gradient Approximation (GGA) and GGA+U methodologies, and considering cubic and orthorhombic perovskite structures for CaxMO3 (x = 0, 0.25, 0.5, 0.75 and 1). The analysis of the calculated voltage-composition profile and volume variations identifies CaMoO3 as the most promising perovskite compound. It combines good electronic conductivity, moderate crystal structure modifications, and activity in the 2-3 V region with several intermediate CaxMoO3 phases. However, we found too large barriers for Ca diffusion (around 2 eV) which are inherent to the perovskite structure. The CaMoO3 perovskite was synthesized, characterized and electrochemically tested, and results confirmed the predicted trends. PMID- 27398630 TI - Modification and cytocompatibility of biocomposited porous PLLA/HA-microspheres scaffolds. AB - Poly(L-lactic acid) and hydroxyapatie (PLLA/HA) composite scaffolds have good properties and suit to use as bone tissue engineering. In this work, hollow HA microspheres (HAM) with poor crystallinity were fabricated by a flame-drying method. The HAM has the potential to be used to release drugs or proteins in addition to improve osteoconductivity. Different ratios of PLLA/HAM were used to prepare porous composite scaffolds using the thermally induced phase separation technique. The HAMs were randomly incorporated into the PLLA porous scaffolds. As the HAMs ratio was increased, the porous composite scaffolds changed from ladder like into isotropic structure. In addition, the compressive strength of PLLA/HAMs composite scaffolds improved first and declined with the increasing of HAMs ratio in the scaffolds. In vitro experiment showed that PLLA/HAMs composite scaffolds improved the attachment, migration, and differentiation of osteoblastic cells. These results demonstrated that the PLLA/HAMs composite scaffolds were superior to plain PLLA scaffold for bone tissue engineering. PMID- 27398631 TI - FTIR assay method for UV inactive drug carisoprodol and identification of degradants by RP-HPLC and ESI-MS. AB - A new method of analysis has been developed for UV inactive drug carisoprodol using FTIR spectroscopy. These methods were validated for various parameters according to ICH guidelines. The proposed method has also been successfully applied for the determination of the drug concentration in a tablet formulation. The method proved to be accurate (mean percentage recovery between 95 and 105%), precise and reproducible (relative standard deviation<2%), while being simple, economical and less time consuming than other methods and can be used for routine estimation of carisoprodol in the pharmaceutical industry. The developed method also implicates its utility for other UV inactive substances. The stability of the drug under various stress conditions was studied and the drug was found to be particularly susceptible to alkaline hydrolysis. Degradation products of the alkaline hydrolysis were detected by RP-HPLC and tentatively identified by ESI MS. PMID- 27398632 TI - Determination of phentermine, N-hydroxyphentermine and mephentermine in urine using dilute and shoot liquid chromatography-tandem mass spectrometry. AB - Nonmedical use of prescription stimulants such as phentermine (PT) has been regulated by law enforcement authorities due to its euphorigenic and relaxing effects. Due to high potential for its abuse, reliable analytical methods were required to detect and identify PT and its metabolite in biological samples. Thus a dilute and shoot liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for simultaneous determination of PT, N hydroxyphentermine (NHOPT) and mephentermine (MPT) in urine. A 5MUL aliquot of diluted urine was injected into the LC-MS/MS system. Chromatographic separation was performed by reversed-phase C18 column with gradient elution for all analytes within 5min. Identification and quantification were based on multiple reaction monitoring (MRM) detection. Linear least-squares regression with a 1/x(2) weighting factor was used to generate a calibration curve and the assay was linear from 50 to 15000ng/mL (PT and MPT) and 5 to 750ng/mL (NHOPT). The intra- and inter-day precisions were within 8.9% while the intra- and inter-day accuracies ranged from -6.2% to 11.2%. The limits of quantification were 3.5ng/mL (PT), 1.5ng/mL (NHOPT) and 1.0ng/mL (MPT). Method validation requirements for selectivity, dilution integrity, matrix effect and stability were satisfied. The applicability of the developed method was examined by analyzing urine samples from drug abusers. PMID- 27398634 TI - Design and synthesis of a new organic receptor and evaluation of colorimetric anion sensing ability in organo-aqueous medium. AB - A new organic receptor has been designed and synthesized by the combination of aromatic dialdehyde with nitro-substituted aminophenol resulting in a Schiff base compound. The receptor exhibited a colorimetric response for F(-) and AcO(-) ion with a distinct color change from pale yellow to red and pink respectively in dry DMSO solvent and yellow to pale greenish yellow in DMSO:H2O (9:1, v/v). UV-Vis titration studies displayed a significant shift in absorption maxima in comparison with the free receptor. The shift could be attributed to the hydrogen bonding interactions between the active anions and the hydroxyl functionality aided by the electron withdrawing nitro substituent on the receptor. (1)H NMR titration and density functionality studies have been performed to understand the nature of interaction of receptor and anions. The lower detection limit of 1.12ppm was obtained in organic media for F(-) ion confirming the real time application of the receptor. PMID- 27398633 TI - Serum metabonomics study of anti-depressive effect of Xiao-Chai-Hu-Tang on rat model of chronic unpredictable mild stress. AB - Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment. PMID- 27398635 TI - Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics. AB - Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics. PMID- 27398637 TI - Ocular surface toxicity from glaucoma topical medications and associated preservatives such as benzalkonium chloride (BAK). AB - INTRODUCTION: This review discusses the evidence concerning the effect of topical medications and their preservatives on the ocular surface in glaucoma patients. The role of topical anti-glaucoma medication remains critical in the management of chronic glaucoma worldwide but the beneficial effects of treatment are counterbalanced by the adverse effects of corneal and conjunctival toxicity. AREAS COVERED: This article covers the effect of topical ocular drops and preservatives, particularly benzalkonium chloride, on the cornea and conjunctiva. Both basic science and clinical evidence will be presented. The first part reviews the relationship between ocular surface disease and benzalkonium chloride and the evidence from non-benzalkonium chloride preserved drops. The second part discusses the effects of benzalkonium chloride on the histopathology of the conjunctiva and its impact on clinical care as well as quality of life. EXPERT OPINION: Topical anti-glaucoma medication will continue to be used in the management of this blinding disease for the foreseeable future. Treatment outcomes will benefit from minimized exposure to benzalkonium chloride. The development of alternative preservatives, preservative-free topical options, and non-drop therapeutics such as drug-eluting systems for the delivery of ocular medications, will be very helpful in the care of glaucoma patients. PMID- 27398636 TI - (123) I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and (123) I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study. AB - OBJECTIVE: To compare the diagnostic value of striatal (123) I-2beta-carbomethoxy 3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123) I-FP-CIT) single photon emission computed tomography (SPECT) and (123) I-metaiodobenzylguanidine ((123) I MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. METHODS: This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. RESULTS: Overall, sensitivity and specificity to DLB were respectively 93% and 100% for (123) I-MIBG myocardial scintigraphy, and 90% and 76% for (123) I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased (123) I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal (123) I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with (123) I-MIBG uptake. INTERPRETATION: (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on (123) I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368-378. PMID- 27398638 TI - PCR analysis is superior to histology for diagnosis of Whipple's disease mimicking seronegative rheumatic diseases. AB - OBJECTIVES: The diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases. METHOD: Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures. RESULTS: Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms. CONCLUSIONS: A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD. PMID- 27398639 TI - Association of Blood Donor Age and Sex With Recipient Survival After Red Blood Cell Transfusion. AB - IMPORTANCE: While red blood cells (RBCs) are administered to improve oxygen delivery and patient outcomes, they also have been associated with potential harm. Unlike solid organ transplantation, the clinical consequences of donor characteristics on recipients have not been evaluated in transfusion medicine. OBJECTIVE: To analyze the association of RBC donor age and sex with the survival of transfusion recipients. DESIGN, SETTING, AND PARTICIPANTS: We established a longitudinal cohort by linking data from a blood collection agency with clinical and administrative data at 4 academic hospitals. MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression models were fitted to evaluate the risk of donor age and sex on transfusion recipient survival. RESULTS: Between October 25, 2006, and December 31, 2013, a total of 30 503 RBC transfusion recipients received 187 960 RBC transfusions from 80 755 unique blood donors. For recipients receiving an RBC unit from younger donors, the risk of death was increased compared with recipients receiving an RBC unit from a donor 40 to 49.9 years old (adjusted hazard ratio, 1.08; 95% CI, 1.06-1.10; P < .001 for donor age range 17-19.9 years and 1.06; 95% CI, 1.04-1.09; P < .001 for donor age range 20-29.9 years). Receiving an RBC transfusion from a female donor was associated with an 8% statistically significant increased risk of death compared with receiving an RBC transfusion from a male donor (adjusted hazard ratio, 1.08; 95% CI, 1.06-1.09; P < .001). CONCLUSIONS AND RELEVANCE: Red blood cell transfusions from younger donors and from female donors were statistically significantly associated with increased mortality. These findings suggest that donor characteristics may affect RBC transfusion outcomes. PMID- 27398640 TI - The Jury Is Still Out on Working Memory Training-Reply. PMID- 27398641 TI - The nitrogen cycle in highly urbanized tropical regions and the effect of river aquifer interactions: The case of Jakarta and the Ciliwung River. AB - Groundwater is extensively used in Jakarta to compensate for the limited public water supply network. Recent observations show a rise in nitrate (NO3(-)) levels in the shallow aquifer, thus pointing at a potential risk for public health. The detected levels are still below national and international regulatory limits for drinking water but a strategy is necessary to contain the growing problem. We combine 3years of available data in the Ciliwung River, the major river flowing through Jakarta, with a distributed river-aquifer interaction model to characterise the impact of urbanisation on the N-cycle of both surface and groundwater systems. Results show that the N-cycle in the river-aquifer system is heterogeneous in space, seasonal dependent (i.e. flow regime) and strongly affected by urban pollution. Results suggest also that although the main sources of N related groundwater pollution are leaking septic tanks, the aquifer interaction with the Ciliwung River may locally have a strong effect on the concentrations. In the general context of pollution control in urban areas, this study demonstrates how advanced process-based models can be efficiently used in combination with field measurements to bring new insights into complex contamination problems. These are essential for more effective and integrated management of water quality in river-aquifer systems. PMID- 27398621 TI - The genetic architecture of type 2 diabetes. AB - The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes. PMID- 27398642 TI - The brain on silent: mind wandering, mindful awareness, and states of mental tranquility. AB - Mind wandering and mindfulness are often described as divergent mental states with opposing effects on cognitive performance and mental health. Spontaneous mind wandering is typically associated with self-reflective states that contribute to negative processing of the past, worrying/fantasizing about the future, and disruption of primary task performance. On the other hand, mindful awareness is frequently described as a focus on present sensory input without cognitive elaboration or emotional reactivity, and is associated with improved task performance and decreased stress-related symptomology. Unfortunately, such distinctions fail to acknowledge similarities and interactions between the two states. Instead of an inverse relationship between mindfulness and mind wandering, a more nuanced characterization of mindfulness may involve skillful toggling back and forth between conceptual and nonconceptual processes and networks supporting each state, to meet the contextually specified demands of the situation. In this article, we present a theoretical analysis and plausible neurocognitive framework of the restful mind, in which we attempt to clarify potentially adaptive contributions of both mind wandering and mindful awareness through the lens of the extant neurocognitive literature on intrinsic network activity, meditation, and emerging descriptions of stillness and nonduality. A neurophenomenological approach to probing modality-specific forms of concentration and nonconceptual awareness is presented that may improve our understanding of the resting state. Implications for future research are discussed. PMID- 27398644 TI - Failure of tension band plating: a case series. AB - Growth modulation with tension band plates (TBP) has been shown to be a very useful method for the treatment of angular deformities in growing children. Recently, we have observed cases of failure where the epiphyseal screw was drawn through the physis into the metaphysis. This study describes a series of children who developed this complication. Patients who developed TBP failure after operative treatment of lower limb angular deformities were identified from the databases at four institutions over a 5-year period. The medical records were reviewed to record demographics, primary diagnoses, details of the operative procedure, development of physeal arrest, and recurrence of the original deformity. Six patients (five girls) with nine implant failures were identified. The mean age of the children at the time of implant insertion was 7.2 years (range, 4-10 years). The primary diagnoses included hypophosphatemic rickets (n=7), congenital pseudoarthrosis of the tibia associated with neurofibromatosis 1 (n=1), and post-traumatic malunion after distal tibial fracture (n=1). Of the nine TBP that presented with the complication, four were inserted into the medial distal femur (one bilateral case), two into the medial proximal tibia (one bilateral case), two into the lateral distal tibia, and one into the medial distal tibia. None of these patients developed physeal growth arrest at the last follow-up as assessed on the latest radiographs. The use of TBP for guided growth in patients younger than 10 years old with rickets, neurofibromatosis, or other conditions that produce osteopenia leads to an increased risk for implant failure. In these cases, it is important to confirm that the epiphyseal screw has good purchase. Patients with these features should be monitored closely for early detection of this complication. PMID- 27398645 TI - The fate of hips that are conservatively treated in multiple epiphyseal dysplasia. AB - We reviewed the radiologic and clinical outcomes of hip joints affected by multiple epiphyseal dysplasia in 40 patients. The average patient age was 9.6 years. All patients were followed up for an average of 7.2 years. No patient underwent surgical treatment. The variances of the center-edge angle and femoral head coverage had the greatest tendency to increase with conservative treatment and follow-up (P=0.011 and 0.015, respectively). The acetabular angle and the acetabular depth index at the first visit and the latest follow-up were statistically significantly different (P=0.046 and 0.027, respectively). According to the Stulberg classification, the severity of hip deformity became less severe with age, but this was not statistically significant (P=0.090). Larger improvements in Harris hip scores were identified after conservative treatment (P=0.003). Favorable midterm outcomes were obtained for the treatment of hip deformity in multiple epiphyseal dysplasia patients by conservative treatment. PMID- 27398646 TI - Corrigendum. PMID- 27398643 TI - Mindfulness meditation-based pain relief: a mechanistic account. AB - Pain is a multidimensional experience that involves interacting sensory, cognitive, and affective factors, rendering the treatment of chronic pain challenging and financially burdensome. Further, the widespread use of opioids to treat chronic pain has led to an opioid epidemic characterized by exponential growth in opioid misuse and addiction. The staggering statistics related to opioid use highlight the importance of developing, testing, and validating fast acting nonpharmacological approaches to treat pain. Mindfulness meditation is a technique that has been found to significantly reduce pain in experimental and clinical settings. The present review delineates findings from recent studies demonstrating that mindfulness meditation significantly attenuates pain through multiple, unique mechanisms-an important consideration for the millions of chronic pain patients seeking narcotic-free, self-facilitated pain therapy. PMID- 27398647 TI - Hepatic expression of FTO and fatty acid metabolic genes changes in response to lipopolysaccharide with alterations in m6A modification of relevant mRNAs in the chicken. AB - The fat mass and obesity associated (FTO) gene, which encodes a demethylase of m6A, has been reported to respond to lipopolysaccharide (LPS) and to serve as a link between inflammation and metabolic responses. The objective of this study was to determine whether LPS-induced changes in the expression of FTO and metabolic genes are associated with alterations of m6A in relevant mRNAs. LPS challenge significantly decreased hepatic mRNA expression of carnitine palmitoyl transferase 1 (CPT1) and CPT2, which coincided with a tendency of higher triglyceride accumulation in the liver. LPS significantly down-regulated the full length cFTO1, yet up-regulated the truncated cFTO4 protein in the liver nuclear extracts. Nuclear protein content of cFTO4 in the liver was negatively correlated with the mRNA abundances of CPT1 (r = 0.629) and CPT2 (r = 0.622). Methylated RNA immunoprecipitation analysis revealed that the m6A level around the translation start site of CPT1 was markably decreased in the liver of LPS-treated chickens. These results indicate that LPS-induced changes in FTO protein expression are associated with alteration of mRNA m6A modification in chicken liver. PMID- 27398648 TI - Small-for-size syndrome in liver transplantation: New horizons to cover with a good launchpad. PMID- 27398649 TI - Kinetically Controlled Chemoselective Cyclization Simplifies the Access to Cyclic and Branched Peptides. AB - A bis(2-sulfanylethyl)amido group reacts significantly faster with cysteinyl peptides when installed on the C-terminal end of a peptide in comparison with the side-chain of Asp and Glu. This property enabled the design of a kinetically controlled chemoselective peptide cyclization reaction, giving straightforward access to cyclic and branched peptides in one pot. PMID- 27398651 TI - The effects of gastrocnemius-soleus muscle forces on ankle biomechanics during triple arthrodesis. AB - This paper presents a finite element model of the ankle, taking into account the effects of muscle forces, determined by a musculoskeletal analysis, to investigate the contact stress distribution in the tibio-talar joint in patients with triple arthrodesis and in normal subjects. Forces of major ankle muscles were simulated and corresponded well with the trend of their EMG signals. These forces were applied to the finite element model to obtain stress distributions for patients with triple arthrodesis and normal subjects in three stages of the gait cycle, i.e. heel strike, midstance, and heel rise. The results demonstrated that the stress distribution patterns of the tibio-talar joint in patients with triple arthrodesis differ from those of normal subjects in investigated gait cycle stages. The mean and standard deviations for maximum stresses in the tibo talar joint in the stance phase for patients and normal subjects were 9.398e7 +/- 1.75e7 and 7.372e7 +/- 4.43e6 Pa, respectively. The maximum von Mises stresses of the tibio-talar joint for all subjects in the stance phase found to be on the lateral side of the inferior surface of the joint. The results also indicate that, in patients with triple arthrodesis, increasing gastrocnemius-soleus muscle force reduces the stress on the medial malleolus compared with normal subjects. Most of stresses in this area are between 45 and 109 kPa, and will decrease to almost 32 kPa in patients after increasing of 40% in gastrocnemius-soleus muscle force. PMID- 27398650 TI - Pembrolizumab (Keytruda). AB - The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20 50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment. PMID- 27398652 TI - A pilot study to explore the experiences of congenitally or early profoundly deafened candidates who receive cochlear implants as adults. AB - OBJECTIVES: To explore the experiences of congenitally or early profoundly deafened candidates who receive cochlear implants as adults. METHODS: Eight congenitally or early profoundly deafened implantees who had received their implants as adults were interviewed using a semi-structured interview technique. Interviews were conducted in the participant's preferred communication mode (oral/aural, SSE, BSL). RESULTS: All participants reported benefit from implantation. Areas of benefit identified correspond with results from similar studies conducted with post-lingually deafened adult implantees. DISCUSSION: Congenitally or early profoundly deafened adults implanted as adults report benefit from cochlear implantation in the following areas: identity, hearing the world, emotional wellbeing. They also commented on their motivation for wanting an implant and the advice they would give to others considering implantation. PMID- 27398654 TI - Scanning sports. PMID- 27398655 TI - Letters. PMID- 27398653 TI - Dynamical Torque in CoxFe3-xO4 Nanocube Thin Films Characterized by Femtosecond Magneto-Optics: A pi-Shift Control of the Magnetization Precession. AB - For spintronic devices excited by a sudden magnetic or optical perturbation, the torque acting on the magnetization plays a key role in its precession and damping. However, the torque itself can be a dynamical quantity via the time dependent anisotropies of the system. A challenging problem for applications is then to disentangle the relative importance of various sources of anisotropies in the dynamical torque, such as the dipolar field, the crystal structure or the shape of the particular interacting magnetic nanostructures. Here, we take advantage of a range of colloidal cobalt ferrite nanocubes assembled in 2D thin films under controlled magnetic fields to demonstrate that the phase, phiPrec, of the precession carries a strong signature of the dynamical anisotropies. Performing femtosecond magneto-optics, we show that phiPrec displays a pi-shift for a particular angle thetaH of an external static magnetic field, H. thetaH is controlled with the cobalt concentration, the laser intensity, as well as the interparticle interactions. Importantly, it is shown that the shape anisotropy, which strongly departs from those of equivalent bulk thin films or individual noninteracting nanoparticles, reveals the essential role played by the interparticle collective effects. This work shows the reliability of a noninvasive optical approach to characterize the dynamical torque in high density magnetic recording media made of organized and interacting nanoparticles. PMID- 27398656 TI - Coming in sportsmedicine. PMID- 27398659 TI - A need to know. PMID- 27398661 TI - Drugs and Self-Confidence. PMID- 27398660 TI - Brief reports. PMID- 27398662 TI - A New Breed of Physicians. PMID- 27398663 TI - Cardiorespiratory Responses to Inversion. AB - In brief: Cardiorespiratory responses to hanging upside down (inversion) were measured in 50 healthy young subjects. Measurements were taken at rest before and after inversion and for three minutes in the head-down position. Both systolic and diastolic blood pressure increased significantly and remained significantly elevated during inversion. Heart rate decreased significantly and remained so during inversion. Respiratory response was unaffected except for a significant increase in oxygen uptake during the first two minutes of inversion. Individuals who use inversion devices should use caution, have blood pressure monitored, and avoid muscle strengthening exercises during inversion. PMID- 27398664 TI - Subdural Hematoma in a High School Football Player. AB - In brief: A high school football player sustained a blow to the head during a game but did not lose consciousness or show immediate neurological impairment. He later developed a subdural hematoma. To help those who provide medical care at sports events diagnose the severity of head injuries quickly and accurately, the authors review the types of concussion, on-field and sideline examinations, and guidelines for returning the athlete to play. They also provide instructions for fitting helmets properly. PMID- 27398665 TI - How I Manage Skier's Thumb. AB - In brief: Skiing, hockey, and boxing, as well as occupational hazards and falls in general, are potential causes of skier's thumb-a sprain of the ulnar support structures of the metacarpophalangeal joint. History, physical characteristics, and the findings on plain and special x-rays are necessary for a correct diagnosis. The mechanism of injury is usually excessive extension or radial deviation of the thumb. Minor sprains can be immobilized by taping. More severe injuries require a thumb spica cast. For acute injuries surgery is necessary to reattach the ulnar collateral ligament to the base of the proximal phalanx. PMID- 27398666 TI - Social Factors in Wrestlers' Health Problems. AB - In brief: Wrestlers are highly motivated by social pressures to win. These pressures, combined with the physical nature of the sport, may result in injury and illness. Wrestlers tend to take seriously only those health problems that prevent participation, regardless of long-term consequences. Preventive measures include good coaching, rigorous rules governing competition, and skilled enforcement of rules by referees. Physicians can improve wrestlers' health by teaching them about nutrition, communicable disease, the hazards of extreme weight loss, and the prevention and care of injuries. Physicians are needed at wrestling meets to improve the care of acute injuries. PMID- 27398667 TI - The Role of the Family Physician in Sports Medicine. AB - In brief: Sports medicine is often considered an orthopedic subspecialty, but family physicians represent the grass roots of athletic care. Millions of competitive and recreational athletes from all age-groups turn to family physicians with their sports-related problems. In this round-table discussion we asked four physicians to talk about the role of the family practitioner in providing comprehensive care, prescribing exercise, and functioning as team physician and educator. They also discuss ethics, the preparticipation screening exam, sources of sports medicine information, and a sports medicine curriculum. PMID- 27398668 TI - The Muscular Overuse Syndrome in Long-Distance Runners. AB - In brief: Indicators of muscular injury from overtraining were studied in 12 male runners during a road race held over 20 days. Dally mileage averaged 17.3 miles per day, twice their regular training distance. Most of the runners reported persistent mild-to-moderate thigh muscle soreness or stiffness. Serum creatine kinase (CK), an enzymatic marker of muscle tissue injury, was elevated on mornings after running but returned to normal values when the runners rested for two days after day 10. Thigh circumference became significantly reduced during the race, suggesting that the unaccustomed high running mileage also produced thigh muscle atrophy. PMID- 27398669 TI - Mountain Medicine: Skill and Ingenuity Within Limits. PMID- 27398670 TI - Football Safety: Are Changes Protecting the Players? PMID- 27398671 TI - History of the Olympic Marathon. AB - Chaos reigned at the early Olympic marathons, when eccentric, unprepared runners took drugs and automobile rides to get to the finish. PMID- 27398672 TI - Improving Coronary Circulation. PMID- 27398673 TI - Artificial Turf Abrasions. PMID- 27398675 TI - Beyond "turn-on" readout: from zero background to signal amplification by combination of magnetic separation and plasmon enhanced fluorescence. AB - By magnetic separation and subsequent plasmon enhanced fluorescence, an assay platform with a signal output from completely "zero" background to fluorescence amplification is achieved, using quantum dots as reporters. So, it well breaks through the conventional "turn-on" strategy in both lower and upper limits. The sensitivity for hyaluronidase sensing is enhanced 10(4)-10(6) times as compared with previous fluorescence methods. PMID- 27398677 TI - IMPACT OF RETINOPATHY SCREENINGS FOR PROSPECTIVE HEART TRANSPLANT CANDIDATES. AB - PURPOSE: To determine the prevalence of retinopathy among patients undergoing heart transplantation screening and to determine the impact of this finding on eligibility for transplantation. METHODS AND PATIENTS: A retrospective case series was collected to perform an institutional review of all inpatient consults for dilated eye examinations on potential heart transplant candidates over 5.5 years-from March 27, 2008 to October 10, 2014. Measured outcomes included the presence or absence of retinopathy and the effect of retinopathy, if present, on a patient's eligibility for cardiac transplantation. RESULTS: A total of 155 heart transplant candidates underwent bedside ophthalmologic examination as part of their heart transplant candidacy workup. Retinopathy was found in 16 (10%) of these patients: diabetic retinopathy in 13 (8.4%) and hypertensive retinopathy in 3 (1.9%). None of these patients were excluded from the transplant candidacy based on the presence of retinopathy. CONCLUSION: On bedside ophthalmologic examination, retinopathy is an uncommon finding among cardiac transplant candidates. Retinopathy did not preclude transplantation in these patients. We question the utility of the present system of bedside ophthalmic consultation of heart transplant candidates. This may not be an optimal allocation of provider resources. Further studies are warranted to determine an appropriate protocol for ocular evaluation of these patients. PMID- 27398676 TI - The Effect and Mechanisms of Proliferative Inhibition of Crocin on Human Leukaemia Jurkat Cells. AB - Targeted therapy is a potentially useful approach for the treatment of T-lineage acute lymphoblastic leukaemia. This study aimed to find a highly effective, low toxic anti-tumour drug and further investigate its mechanisms. Jurkat cells were used as the object and were stimulated by different concentrations of crocin. By cell count, growth curve, MTT method for the detection of cell proliferation, annexin V/propidium iodide (PI) method for the apoptosis rates, and reverse transcription-polymerase chain reaction (RT-PCR) for bcl-2 and bax gene expression, the effect and mechanisms of proliferative inhibition of crocin on Jurkat cells were further explored. Crocin promoted Jurkat cell apoptosis and inhibited cell growth, in a dose-time-dependent manner. The mechanism might be related to the inhibition of bcl-2 gene expression and the promotion of bax gene expression. These results suggest that crocin can be used as a suitable clinical agent for the treatment of T-lineage acute lymphoblastic leukaemia. PMID- 27398678 TI - Discrimination in Degradability of Soil Pyrogenic Organic Matter Follows a Return On-Energy-Investment Principle. AB - A fundamental understanding of biodegradability is central to elucidating the role(s) of pyrogenic organic matter (PyOM) in biogeochemical cycles. Since microbial community and ecosystem dynamics are driven by net energy flows, then a quantitative assessment of energy value versus energy requirement for oxidation of PyOM should yield important insights into their biodegradability. We used bomb calorimetry, stepwise isothermal thermogravimetric analysis (isoTGA), and 5-year in situ bidegradation data to develop energy-biodegradability relationships for a suite of plant- and manure-derived PyOM (n = 10). The net energy value (DeltaE) for PyOM was between 4.0 and 175 kJ mol(-1); with manure-derived PyOM having the highest DeltaE. Thermal-oxidation activation energy (Ea) requirements ranged from 51 to 125 kJ mol(-1), with wood-derived PyOM having the highest Ea requirements. We propose a return-on-investment (ROI) parameter (DeltaE/Ea) for differentiating short-to-medium term biodegradability of PyOM and deciphering if biodegradation will most likely proceed via cometabolism (ROI < 1) or direct metabolism (ROI >= 1). The ROI-biodegradability relationship was sigmoidal with higher biodegradability associated with PyOM of higher ROI; indicating that microbes exhibit a higher preference for "high investment value" PyOM. PMID- 27398679 TI - Mixed-Valence Molecular Unit for Quantum Cellular Automata: Beyond the Born Oppenheimer Paradigm through the Symmetry-Assisted Vibronic Approach. AB - In this article, we focus on the electron-vibrational problem of the tetrameric mixed-valence (MV) complexes proposed for implementation as four-dot molecular quantum cellular automata (mQCA).1 Although the adiabatic approximation explored in ref 2 is an appropriate tool for the qualitative analysis of the basic characteristics of mQCA, like vibronic trapping of the electrons encoding binary information and cell-cell response, it loses its accuracy providing moderate vibronic coupling and fails in the description of the discrete pattern of the vibronic levels. Therefore, a precise solution of the quantum-mechanical vibronic problem is of primary importance for the evaluation of the shapes of the electron transfer optical absorption bands and quantitative analysis of the main parameters of tetrameric quantum cells. Here, we go beyond the Born-Oppenheimer paradigm and present a solution of the quantum-mechanical pseudo Jahn-Teller (JT) vibronic problem in bielectronic MV species (exemplified by the tetra-ruthenium complexes) based on the recently developed symmetry-assisted approach.3,4 The mathematical approach to the vibronic eigenproblem takes into consideration the point symmetry basis, and therefore, the total matrix of the JT Hamiltonian is blocked to the maximum extent. The submatrices correspond to the irreducible representations (irreps) of the point group. With this tool, we also extend the theory of the mQCA cell beyond the limit of prevailing Coulomb repulsion in the electronic pair (adopted in ref 2), and therefore, the general pseudo-JT problems for spin-singlet ((1)B1g, 2(1)A1g, (1)B2g, (1)Eu) ? (b1g + eu) and spin-triplet states ((3)A2g, (3)B1g, 2(3)Eu) ? (b1g + eu) in a square-planar bielectronic system are solved. The obtained symmetry-adapted electron-vibrational functions are employed for the calculation of the profiles (shape functions) of the charge transfer absorption bands in the tetrameric MV complexes and for the discussion of the magnetic properties. PMID- 27398680 TI - Probing the binding of Cu(2+) ions to a fragment of the Abeta(1-42) polypeptide using fluorescence spectroscopy, isothermal titration calorimetry and molecular dynamics simulations. AB - Steady-state and time-resolved fluorescence quenching measurements supported by isothermal titration calorimetry (ITC) and molecular dynamics simulations (MD), with the NMR-derived restraints, were used to investigate the interactions of Cu(2+) ions with a fragment of the Abeta(1-42) polypeptide, Abeta(5-16) with the following sequence: Ac-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-NH2, denoted as HZ1. The studies presented in this paper, when compared with our previous results (Makowska et al., Spectrochim. Acta A 153: 451-456), show that the affinity of the peptide to metal ions is conformation-dependent. All the measurements were carried out in 20mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer solution, pH6.0. The Stern-Volmer equations, along with spectroscopic observations, were used to determine the quenching and binding parameters. The obtained results unequivocally suggest that Cu(2+) ions quench the fluorescence of HZ1 only through a static quenching mechanism, in contrast to the fragment from the N-terminal part of the FPB28 protein, with sequence Ac-Tyr-Lys-Thr-Ala Asp-Gly-Lys-Thr-Tyr- NH2 (D9) and its derivative with a single point mutation: Ac Tyr-Lys-Thr-Ala-Asn-Gly-Lys-Thr-Tyr- NH2 (D9_M), where dynamic quenching occurred. The thermodynamic parameters (DeltaITCH, DeltaITCS) for the interactions between Cu(2+) ions and the HZ1 peptide were determined from the calorimetric data. The conditional thermodynamic parameters suggest that, under the experimental conditions, the formation of the Cu(2+)-HZ1 complex is both an enthalpy and entropy driven process. PMID- 27398681 TI - Concise Synthesis of Astellatol Core Skeleton. AB - A ten-step, enantiospecific synthesis of the highly challenging core skeleton of sesterterpenoid astellatol has been achieved. Key transformations of this strategy include a facile, convergent construction of the tricyclic motif and a SmI2 -induced reductive radical cyclization that forms the pivotal cyclobutane ring. PMID- 27398682 TI - Video-Assisted Thoracoscopic Resection of a Noninvasive Thymoma in a Cat with Myasthenia Gravis Using Low-Pressure Carbon Dioxide Insufflation. AB - OBJECTIVE: To report the use of low-pressure carbon dioxide insufflation during video-assisted thoracoscopic surgery for resection of a noninvasive thymoma in a cat with secondary myasthenia gravis. STUDY DESIGN: Clinical case report. ANIMAL: Client-owned cat. METHODS: An 11-year-old castrated male domestic shorthair cat was examined for generalized weakness, voice change, hypersalivation, hyporexia, vomiting, coughing, and gagging. Thoracic ultrasound revealed a cranial mediastinal mass for which cytology was consistent with a thymoma (or lymphoid tissue). Acetylcholine receptor antibody concentration was elevated at 3.16 mmol/L (reference interval < 0.3 mmol/L). Thoracic computed tomography showed two round, contrast-enhancing structures in the cranioventral mediastinum identified as the sternal lymph node and a cranial mediastinal mass (11 * 17 * 24 mm). A presumptive diagnosis of thymoma with paraneoplastic myasthenia gravis was made and surgical resection of both mediastinal masses was recommended. RESULTS: Video assisted thoracoscopic resection of the cranial mediastinal mass and sternal lymph node were performed with low-pressure carbon dioxide insufflation maintained at an intrathoracic pressure of 2-3 mmHg. The cat recovered from surgery without serious complications. Nineteen months after surgery, the cat developed hind limb stiffness. Thoracic radiographs ruled out a cranial mediastinal mass or megaesophagus. Acetylcholine receptor antibody concentration remained elevated at 2.72 mmol/L. CONCLUSION: Low-pressure thoracic insufflation facilitated video-assisted thoracoscopic resection of cranial mediastinal masses in this cat. PMID- 27398684 TI - I'm Still Me: Inspiration and Instruction from Individuals with Brain Cancer. AB - Individuals with brain cancer face many challenges, including threats to cognition, personality, and sensory and motor functioning. These can alter one's sense of identity and result in despair. Chaplain-led spiritual interviews were conducted with 19 patients with brain cancer as part of a larger spiritual legacy intervention called "Hear My Voice." The majority was female (58%), married (68%) and had aggressive/advanced tumors (63%). Participants were 22-68 years of age and expressed the following religious affiliations: Protestant (42%), Catholic (21%), Muslim (5%), and none (32%). Framework analysis was applied to reduce and understand the interview data. Primary codes were relationships with: God or the spiritual, others, and self. Brain cancer was reported to deepen and enrich patients' commitment to these relationships. Struggle and grief were also revealed. Results suggest the continued vitality, growth and generativity of these participants and provide insight for chaplains and others on the medical team. PMID- 27398685 TI - Effects of different warm-up modalities on power output during the high pull. AB - This study compared the effects of six warm-up modalities on peak power output (PPO) during the high-pull exercise. Nine resistance-trained males completed six trials using different warm-ups: high-pull specific (HPS), cycle, whole body vibration (WBV), cycle+HPS, WBV+HPS and a control. Intramuscular temperature (Tm) was increased by 2 degrees C using WBV or cycling. PPO, Tm and electromyography (EMG) were recorded during each trial. Two high-pulls were performed prior to and 3 min after participants completed the warm-up. The greatest increase in PPO occurred with HPS (232.8 +/- 89.7 W, P < 0.001); however, this was not different to combined warm-ups (cycle+HPS 158.6 +/- 121.1 W; WBV+HPS 177.3 +/- 93.3 W, P = 1.00). These modalities increased PPO to a greater extent than those that did not involve HPS (all P < 0.05). HPS took the shortest time to complete, compared to the other conditions (P < 0.05). EMG did not differ from pre to post warm-up or between modalities in any of the muscles investigated. No change in Tm occurred in warm-ups that did not include cycling or WBV. These results suggest that a movement-specific warm-up improves performance more than temperature-related warm ups. Therefore, mechanisms other than increased muscle temperature and activation may be important for improving short-term PPO. PMID- 27398686 TI - Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials. AB - PURPOSE: The average delay from first seizure to diagnosis of psychogenic non epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. METHODS: Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. RESULTS: Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2-3.5 years) based on an exponential model as 10 to the mean of log10 delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t=3.6, p=0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t=-0.9, p=0.38). CONCLUSION: Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials. PMID- 27398687 TI - Do demographic and socio-economic characteristics of women with epilepsy influence contact with joint obstetric/neurology services in Northern Ireland?: Women with epilepsy and joint obstetric/neurology services. AB - PURPOSE: Care of pregnant women with epilepsy (WWE) should be shared between an epilepsy specialist and obstetrician. Joint care is provided by the regional, but not peripheral, maternity units in Northern Ireland (NI). We investigated whether demographic and socio-economic factors influenced access of joint obstetric/neurology services. METHOD: Data on WWE delivering between 1st January 2012 and 31st December 2014 were collected. Demographic (age, parity, Trust residence) and socio-economic (employment status, deprivation level) factors were compared between three groups: (1) women delivering at the regional unit from its catchment, (2) women delivering at the regional unit from outside its catchment and (3) women delivering at peripheral units. RESULTS: 447 WWE delivered in the 3 year period. 48% (214/447) and 52% (233/447) delivered at regional and peripheral units respectively. 42% delivering at the regional unit were from its catchment and 58% outside. There was no difference in parity, employment status or deprivation of WWE from outside the regional unit catchment who accessed joint services and those who did not. Trust residence was the strongest predictor of delivery location with women from adjacent Trusts over 90% less likely to deliver at peripheral units. Maternal age was also a predictor of delivery location with a woman aged 30 being 50% less likely to deliver at a peripheral unit than one aged 20. CONCLUSIONS: 52% of all WWE and 63% outside the regional unit catchment do not access the joint service. Service models which deliver improved access should focus on those in geographically distant locations and of younger age. PMID- 27398688 TI - Multivisceral resection for occlusive colorectal cancer: Is it justified? AB - BACKGROUND: The only possibility of curative surgery in primary T4, locally advanced, adherent colorectal carcinoma (LAACRC) or recurrent disease with infiltration of adjacent organs is the en bloc resection of the invaded structures to achieve clear surgical margins (R0). The role of extended resections for occlusive LAACRC remains unclear. We report on our experience on Multivisceral resections (MVR) for LAACRC patients between 2003 and 2012. METHODS: Twenty-two patients, who were treated with MVR with curative purpose for non-metastatic disease were recruited. General epidemiologic data, clinical findings, surgical treatment and/or multimodal therapy, histo-pathological examination and follow-up were collected. In addition post-operative complications were classified. Patients with occlusive LAACRC (n = 6) were compared to patients with uncomplicated presentation (n = 16) defined according to the UICC classification. RESULTS: No statistically significant differences were observed between the two groups, in terms of median age, gender and localization of tumors. R0 resection was performed in 14 (87.5%) patients with uncomplicated tumors and in all patients with occlusive LAACRC. R1 resection was performed in 2/16 (12.5%) patients with uncomplicated disease. No peri-operative mortality was reported in patients of both groups. In the group of uncomplicated tumors, 11 patients (68.7%) were classified as pathological (p)T4 and 5 patients (31.2%) were classified pT3 whereas in the group of occlusive LAACRC the majority of patients were classified as pT4 (83.3%). Lymph node involvement occurred in 9 patients (56.2%) of the fist group and in two patients (33.3%) of the second group, respectively. The 3-year survival rates in all patients with both uncomplicated and occlusive diseases were 58.4% and 33.3%, respectively. The 3 years survival of patients with locally advanced adherent rectal cancer was significantly lower than the observed survival of patients with colon cancer (p < 0.0001). CONCLUSION: MVR offers cure (R0 resections) in uncomplicated and obstructive LAACRC with three years survival in 40% of patients. Patients affected by rectal cancer with occlusive disease showed significantly decreased survival in comparison with those affected by colon cancer. PMID- 27398689 TI - Percutaneous compression plate versus dynamic hip screw for treatment of intertrochanteric hip fractures: A overview of systematic reviews and update meta analysis of randomized controlled trials. AB - PURPOSE: Intertrochanteric hip fractures lead to high morbidity and mortality rates. As a minimally invasive technique, many studies reported the efficacy of PCCP for the treatment of intertrochanteric fractures, but the controversy still existed in some outcomes. The purpose of this study was to evaluate the efficacy of PCCP and DHS by a overview of systematic reviews and well-designed, comprehensive update meta-analysis. METHODS: PUBMED, SCOPUS, CCRCT, WANFANG and CNKI database were searched in all languages published up to April 2016. Systematic reviews and randomized controlled trials reporting outcomes of PCCP and DHS for intertrochanteric fractures were included. Meta-analyses comparing the two techniques were performed according to the Cochrane Handbook. RESULTS: Five original trials and four systematic reviews met the inclusion criteria. Meta analyses showed that the blood loss [SMD = -2.35, 95%CI(-4.26--0.44)], transfusion volume [SMD = -0.26, 95%CI(-0.47--0.06)] and complications [RR = 0.33, 95%CI(0.14-0.77)] was statistically less in PCCP group than DHS group while there was no significant difference between two groups in mortality rate, transfusion rate and length of hospital day. CONCLUSIONS: PCCP is recommended to treat intertrochanteric hip fractures as an alternative minimally invasive method. More high-quality, randomized controlled trials that are adequately powered are needed to further evaluate the efficacy of PCCP and DHS. PMID- 27398690 TI - Comparison of surgical and endovascular approaches in the management of multiple intracranial aneurysms. AB - OBJECTIVE: To investigate the outcomes and safety of endovascular compared with surgical clipping for multiple intracranial aneurysms. MATERIAL AND METHODS: 98 patients with 260 multiple intracranial aneurysms were treated with endovascular, surgical clipping, combined treatment, and observation. Data were retrospectively studied following treatment and at follow-up. RESULTS: In the endovascular group, 44 aneurysms were treated with coils only and 29 aneurysms were treated with stent deployment. The complete occlusion rate was 65%, and the total complication rate was 12% with no permanent deficit. After angiographic follow-up for 1-90 (mean 62) months, the total recurrence rate was 18.3%. In the clipping group, 65 aneurysms were clipped. The complete occlusion rate was 90.8%, and the complication rate was 10.9% with 1 permanent deficit. After follow-up for 11-71 (mean 49) months, the angiographic recurrence rate was 1.5%. In the combination group, 20 aneurysms were treated endovascularly. The complete occlusion rate was 78.9%, and the complication rate was 15.8% with no permanent deficit. Twenty eight aneurysms were treated surgically with the complete occlusion rate of 89.3%, the complication rate of 20% and 3 permanent deficits. After follow-up for 1-93 (mean 58) months, the angiographic recurrence rate was 33.3% for embolization and 3.6% for clipping. Seventy-four aneurysms for observation had 2.7% regrowth rate within 1-3 years. CONCLUSION: Endovascular embolization has an accepted complication rate but no neurological deficits compared with surgical clipping and may be a better approach for multiple intracranial aneurysms than surgical clipping. PMID- 27398691 TI - C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis. AB - Gastric cancer is one of the most common cancers and the third leading cause of cancer death worldwide. A number of chemokines and cytokines play important roles in the progress of gastric cancer. The roles of C-C motif chemokine ligand 5 (CCL5) in gastric cancer remain unclear. Here, we retrospectively report an analysis of 105 patients with gastric cancer. Increased levels of CCL5 in circulation were correlated with more advanced T and N stages, poorly- or un differentiated histological types, peritoneal metastasis, higher rates of residual tumor, and shorter survivals. Patients in the CCL5 High Group had stronger CCL5 immunohistochemistry (IHC) staining in tumor beds. Circulating CCL5 concentrations before surgery are a good biomarker for occult peritoneal metastasis. Elevated levels of serum CCL5, along with strong IHC CCL5 staining and poorly- or un-differentiated cancer are predictors for poorer outcomes. In conclusion, increased serum levels of CCL5 can be used to predict peritoneal dissemination and a poorer prognosis. PMID- 27398692 TI - Synthesis and Photocatalytic Reactivity of Vinylsulfonium Ylides. AB - Although sulfur ylides are textbook reagents in organic synthesis, surprisingly little variation of substituents on sulfur is usually observed. In particular, vinylsulfonium ylides have been neglected so far. Herein, we present a study on their synthesis and reactivity, including interesting behavior under photocatalytic conditions. PMID- 27398693 TI - One-Step Catalytic Synthesis of CuO/Cu2O in a Graphitized Porous C Matrix Derived from the Cu-Based Metal-Organic Framework for Li- and Na-Ion Batteries. AB - The hybrid composite electrode comprising CuO and Cu2O micronanoparticles in a highly graphitized porous C matrix (CuO/Cu2O-GPC) has a rational design and is a favorable approach to increasing the rate capability and reversible capacity of metal oxide negative materials for Li- and Na-ion batteries. CuO/Cu2O-GPC is synthesized through a Cu-based metal-organic framework via a one-step thermal transformation process. The electrochemical performances of the CuO/Cu2O-GPC negative electrode in Li- and Na-ion batteries are systematically studied and exhibit excellent capacities of 887.3 mAh g(-1) at 60 mA g(-1) after 200 cycles in a Li-ion battery and 302.9 mAh g(-1) at 50 mA g(-1) after 200 cycles in a Na ion battery. The high electrochemical stability was obtained via the rational strategy, mainly owing to the synergy effect of the CuO and Cu2O micronanoparticles and highly graphitized porous C formed by catalytic graphitization of Cu nanoparticles. Owing to the simple one-step thermal transformation process and resulting high electrochemical performance, CuO/Cu2O GPC is one of the prospective negative active materials for rechargeable Li- and Na-ion batteries. PMID- 27398694 TI - Cybersex Addiction: A Study on Spanish College Students. AB - The aim of this study was to determine the type and frequency of online sexual practices among Spanish college students, the prevalence of risk and pathological cybersex use profiles, and the correlates/predictors of this behavior. Participants were 1,557 males and females between 18 and 25 years old. Results showed that cybersex use is not as frequent as that documented in other Western countries. However, a significant percentage of participants with a risky (8.6%) or pathological (1.7% in men and 0.1% in women) profile was identified. Finally, we found a set of variables that, in interaction with gender, explains 58% of the variance for cybersex addiction scores. PMID- 27398696 TI - Need for a National Evaluation System for Health Technology. PMID- 27398697 TI - A Randomized Clinical Trial of an Intensive Behavior Education Program in Gestational Diabetes Mellitus Women Designed to Improve Glucose Levels on the 2 Hour Oral Glucose Tolerance Test. AB - Objective To evaluate whether women with gestational diabetes mellitus (GDM) enrolled in an intensive behavior education program (IBEP) demonstrate lower mean fasting glucose levels on the 2-hour 75 g oral glucose tolerance test (2-hour OGTT) at 6 to 12 weeks postpartum compared with women who undergo routine GDM management. Study Design A prospective randomized controlled trial of women diagnosed with GDM was conducted. Exclusion criteria were GDM diagnosis >= 33 weeks or < 20 weeks. Women were randomly assigned to one of two treatment arms: (1) routine GDM management or (2) an IBEP. Women underwent a 2-hour OGTT at 6 to 12 weeks postpartum. Fisher exact test, t-test, and Wilcoxon rank sum test were used as appropriate. Results Of the 101 women randomized, 49 were assigned to IBEP and 52 received routine GDM management. There was no difference in mean fasting and 2-hour glucose levels on the postpartum 2-hour OGTT between the IBEP and routine management group (88.5 +/- 22.9 mg/dL vs. 85.2 +/- 13.3 mg/dL, p = 0.49 and 109.8 +/- 38.5 mg/dL vs. 109.4 +/- 40.8 mg/dL, p = 0.97, respectively). Conclusion GDM women enrolled in a healthy lifestyle intervention program did not demonstrate lower glucose values on the postpartum 2-hour OGTT. PMID- 27398698 TI - Utility of the Simplified Bishop Score in Spontaneous Labor. AB - Objective The objective of this study was to evaluate the relationship between the simplified Bishop score (SBS) on admission for labor and subsequent labor outcomes to identify women at higher risk for cesareans. Study Design This was a secondary analysis of a prospective cohort study of 4,733 singleton pregnancies. Adjusted odds ratios (aOR) were calculated comparing outcomes in women with an unfavorable SBS <= 5 to women with a favorable SBS > 5. A favorable SBS was compared with the individual parameters of dilation, effacement, and station. The primary outcome was vaginal delivery. Secondary outcomes were prolonged first stage, completion of first stage, oxytocin augmentation, and prolonged second stage. Results 47.8% of the patients admitted in labor had an unfavorable SBS. Nulliparous and multiparous patients with a favorable SBS were more likely to have a vaginal delivery (aOR 1.96, 95% confidence intervals [CI] 1.49-2.57; aOR 1.91, 95% CI 1.44-2.53) and less likely to require oxytocin augmentation (aOR 0.34, 95% CI 0.28-0.42; aOR 0.26, 95% CI 0.22-0.30. Compared with dilation alone, the SBS in its entirety was associated with a higher likelihood of vaginal delivery in nulliparous. Conclusion An unfavorable SBS on admission for labor is associated with a decreased likelihood of having a vaginal delivery. PMID- 27398699 TI - Placental Weight in Pregnant Women with Type 1 Diabetes Mellitus: The Association with Fetal Growth. AB - Objective To determine the association between placental weight (PW) and large for gestational age (LGA) in women with type 1 diabetes mellitus (T1DM) and whether glycemic control modifies the association. Study Design In a retrospective analysis of a cohort of women with T1DM, poor glycemic control was defined as glycohemoglobin A1(HbA1)>= 8.5% (>=2 standard deviations [SD] above mean), and LGA as birth weight > 90th percentile, according to gestation, race, and sex. Multivariable logistic regression was used for analysis. Stratified analyses (HbA1 < 8.5% vs. HbA1 >= 8.5%) assessed the role of glycemic control on association between PW and LGA. Results PW in 302 pregnancies was positively associated with LGA (first vs. fourth quartile of PW; odds ratio [OR] = 9.56; 95% confidence interval [CI]: 4.14-22.08). Association varied significantly by glycemic control in the first trimester, but not in the second and third trimesters. For women with first trimester HbA1 concentration < 8.5%, there was no statistically significant association; however, with HbA1 >= 8.5%, there was a strong association (OR = 13.40, 95% CI: 3.31, 54.27). Conclusion There was a significant positive association between PW and LGA in infants of women with T1DM, particularly evident in pregnancies with poor glycemic control during the first trimester, highlighting the importance of achieving good glycemic control early in gestation. PMID- 27398700 TI - The History and Contributions of the Diabetes in Pregnancy Study Group of North America (1997-2015). AB - The Diabetes in Pregnancy Study Group of North America (DPSG-NA) was founded in 1997 in San Antonio, Texas, out of the recognition that the field of maternal fetal medicine should support and conduct research to address the specialized needs of pregnant women with type 1, type 2, or gestational diabetes mellitus. Since its inception, the DPSG-NA meetings have become a vehicle for the dissemination of data, gathered through collaboration among basic, translational, and clinical researchers and care centers, both in the United States and abroad. Although the meetings cover a range of topics related to diabetes in pregnancy, they have often highlighted a major, timely issue. Utilizing presentations, roundtable discussions, and debates, members of the DPSG-NA discussed the latest research, treatments, and approaches to significantly improve the health and wellbeing of pregnant women with diabetes and their offspring. The following commentary highlights the major contributions of each meeting. PMID- 27398701 TI - Contrast Enema and Risk of Sepsis in Premature Babies: A 12-Year Retrospective Study. AB - Objective The objective of this study was to investigate the association between contrast enema (CE) and clinical sepsis (CS) in premature babies (PB) and the role of antibiotics (ABs) in its prevention. Study Design A retrospective electronic chart review of preterm babies, who underwent CE during their stay in the neonatal intensive care unit. Group I includes CEs of babies exposed to AB during or within 48 hours of the procedure. Group II represents CEs of babies, not exposed to AB. Variables for both groups were collected and analyzed. Results There were 161 CEs performed in 133 babies. The overall incidence of CS after CE in preterm babies was 21/160 cases (13%). The incidence was significantly lower in Group I (1/79, 1.2%), compared with Group II (20/81, 24.7%) (p < 0.001). Six (30%) of the 20 babies from Group II had positive blood culture and all 20 required AB after the CE. There were no statistical differences in the variables between the two groups. Conclusion There is a possible association between CE and CS in preterm babies. ABs given during or before the procedure prevent this complication. PMID- 27398702 TI - Does Infection During Pregnancy Outside of the Time of Delivery Increase the Risk of Cerebral Palsy? AB - Objective We sought to evaluate whether maternal antepartum infection (excluding chorioamnionitis) is associated with cerebral palsy (CP). Study Design This is a secondary analysis from a multicenter trial in women at risk of preterm delivery who received antenatal magnesium sulfate versus placebo. We compared the risk of CP in the children of women who had evidence of antepartum infection over the course of pregnancy to those women who had no evidence of antepartum infection during pregnancy. Results Within a cohort of 2,251 women who met our inclusion criteria, 1,350 women had no history of infection in pregnancy and 801 women had a history of some type of antepartum infection during pregnancy. The incidence of CP was similar between the two groups (4.9 vs 5.0%; p = 0.917). After adjustment for maternal and obstetric confounders, we observed no significantly increased risk of CP among infants born to women with evidence of antepartum infection; (adjusted relative risk [aRR], 1.09 (0.72, 1.66); p = 0.68). Conclusion Compared with women with no evidence of antepartum infection during pregnancy, those women with infections excluding chorioamnionitis may not be at an increased risk of delivering an infant with CP. PMID- 27398703 TI - Characterizing Gestational Weight Gain According to Institute of Medicine Guidelines in Women with Type 1 Diabetes Mellitus: Association with Maternal and Perinatal Outcome. AB - Objective This study aims to evaluate the association between gestational weight gain (GWG) defined by the current Institute of Medicine (IOM) guidelines and pregnancy outcomes in women with type 1 diabetes mellitus (DM). Study design This is a secondary analysis of a cohort of 293 pregnancies of women with type 1 DM between 24 and 41 weeks' gestation. Women were categorized according to GWG per week over the second and third trimester: below, within, and above the IOM guidelines. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for maternal and neonatal outcomes, controlling for covariates and confounders (referent: GWG within the IOM guidelines). Results Of the 293 women, there were 49 women (16.7%) with the GWG below the IOM guidelines, 86 women (29.4%) with the GWG within the IOM guidelines, and 158 women (53.9%) with the GWG above the IOM guidelines. Women with the GWG above the IOM guidelines had a higher risk of macrosomia and neonatal hyperbilirubinemia (aOR: 2.78; 95% CI: 1.23-6.30 and 2.31; 1.22-4.35, respectively). Conclusion GWG above the IOM guidelines is associated with an increased risk of macrosomia and neonatal hyperbilirubinemia. Maintaining GWG within the IOM guidelines may decrease the risk of excessive fetal growth and neonatal hyperbilirubinemia in infants of women with type 1 DM. PMID- 27398705 TI - Apnea after Routine Eye Examinations in Premature Infants. AB - Objective To determine the frequency of cardiorespiratory events following routine exams for retinopathy of prematurity (ROP). Study Design This is a retrospective review of 79 premature infants in the neonatal intensive care unit at the University of Rochester Medical Center. The baseline for each infant (mean cardiorespiratory events in the 72 hours before the exam) was compared with the number of cardiorespiratory events during the subsequent 24 hours using generalized estimating equation and the Mantel-Haenszel chi-square test to determine if there was an association between cardiorespiratory events and potential risk factors. Results Approximately 19 to 25% of infants experienced an increase in cardiorespiratory events in the 24 hours following their eye exams. These newborns were generally of a younger gestational age and lower birthweight. Conclusion The frequency of cardiorespiratory events following routine ROP exams is similar to that following routine immunizations in this population. Thus, in infants being continuously monitored during the 24 hours after the exam, alterations in medical care in the absence of other clinical signs suggestive of sepsis or clinical deterioration may not be required, limiting unnecessary antibiotic exposure, prolonged caffeine administration, unwarranted gastroesophageal reflux treatment, and undue family stress. PMID- 27398704 TI - Induction of Labor in Women with Oligohydramnios: Misoprostol Compared with Prostaglandin E2. AB - Objective To compare perinatal outcomes in women with oligohydramnios and an unfavorable cervix undergoing labor induction with misoprostol to prostaglandin E2. Study Design We conducted a secondary analysis of women with oligohydramnios undergoing labor induction in the Consortium on Safe Labor study (2002-2008). Oligohydramnios was recorded in the medical chart. We evaluated perinatal outcomes. We limited the analysis to women with an unfavorable cervix defined by simplified Bishop score <= 4. Misoprostol was compared with prostaglandin E2. Women could have received oxytocin, underwent mechanical dilation, or had artificial rupture of membranes, but women who underwent induction with both misoprostol and prostaglandin E2 were excluded. We calculated adjusted odds ratios with 95% confidence intervals, controlling for maternal age, maternal body mass index (kg/m2), parity, and mechanical dilation. Results Among women with oligohydramnios and an unfavorable cervix who underwent induction of labor, 141 (39.4%) received misoprostol and 217 (60.6%) received prostaglandin E2. There were no significant differences in cesarean delivery, chorioamnionitis, postpartum hemorrhage, transfusion, neonatal intensive care unit (NICU) admission, NICU stay > 72 hours, mechanical ventilation, and neonatal sepsis. Conclusion In women with oligohydramnios and an unfavorable cervix, induction of labor with misoprostol was comparable to prostaglandin E2. PMID- 27398707 TI - Advanced Maternal Age and the Risk of Major Congenital Anomalies. AB - Objective This study aims to determine if advanced maternal age (AMA) is a risk factor for major congenital anomalies, in the absence of aneuploidy. Study Design Retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over a 19-year study period. Aneuploid fetuses were excluded. Study groups were defined by maternal age <= 34 and >= 35 years. The primary outcome was the presence of one or more major anomalies diagnosed at the second trimester ultrasound. Univariable and multivariable logistic regression analyses were used to estimate the risk of major anomalies in AMA patients. Results Of 76,156 euploid fetuses, 2.4% (n = 1,804) were diagnosed with a major anomaly. There was a significant decrease in the incidence of major fetal anomalies with increasing maternal age until the threshold of age 35 (p < 0.001). Being AMA was significantly associated with an overall decreased risk for major fetal anomalies (adjusted odds ratio: 0.59, 95% confidence interval: 0.52 0.66). The subgroup analysis demonstrated similar results for women >= 40 years of age. Conclusion AMA is associated with an overall decreased risk for major anomalies. These findings may suggest that the "all or nothing" phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive. PMID- 27398706 TI - Cell-Free Total and Fetal DNA in First Trimester Maternal Serum and Subsequent Development of Preeclampsia. AB - Objective The objective of this study was to assess the relationship between first trimester cell-free total and fetal DNA in maternal plasma and the subsequent development of preeclampsia. Study Design Nested case-control study of patients enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies prediction study of 175 women who did and 175 women who did not develop preeclampsia. The predictive values of cell-free total and fetal DNA and the subsequent development of preeclampsia were measured using receiver operating characteristic curves. Results Cell-free total DNA was higher in African American (median; 25-75%; 6.15; 0.14-28.73; p = 0.02) and Hispanic (4.95; 0.20-26.82; p = 0.037) compared with white women (2.33; 0.03-13.10). Levels of cell-free total DNA were also associated with maternal body mass index (BMI) (p = 0.02). Cell free total DNA levels were similar between women who later developed preeclampsia (3.52; 0.11-25.3) and controls (3.74; 0.12-21.14, p = 0.96). Conclusion There is no significant difference in levels of cell-free total DNA in the first trimester in women who subsequently develop preeclampsia. Levels of cell-free total DNA in the first trimester are increased in African American and Hispanic compared with white women, and levels increase with increasing BMI. PMID- 27398708 TI - Manual and Cognitive Dual Tasks Contribute to Fall-Risk Differentiation in Posturography Measures. AB - Falls occur in 33% of older adults each year, some leading to moderate to severe injuries. To reduce falls and fall-related injuries, it is important to identify individuals with subtle risk factors elevating their likelihood of falling. The objective of this study was to determine how postural sway measures differed between fallers and nonfallers under standard and dual-task conditions. Quietstanding posturography measures were collected from 150 older adults during standard, cognitive, manual, and cognitive+manual tasks, and analyzed through traditional and nonlinear analyses. Of the traditional measures, M/L sway range and 95% confidence ellipse sway area showed statistically significant differences in all 4 test conditions between fallers and nonfallers. Although the manual dual task showed the most stable balance, effect sizes demonstrated larger differences between fallers and nonfallers. Nonlinear analysis revealed M/L sample entropy and M/L alpha-scaling exponent differentiating between fallers and nonfallers, with the cognitive task demonstrating larger differences. Based on the results, it is recommended to: (1) apply M/L sway range and 95% confidence ellipse area, (2) use the manual task to differentiate between fallers and nonfallers when using traditional analyses, and (3) use the cognitive task and M/L alpha and M/L sample entropy when using nonlinear analyses. PMID- 27398710 TI - Imaging of Anterior Nucleus of Thalamus Using 1.5T MRI for Deep Brain Stimulation Targeting in Refractory Epilepsy. AB - BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an evolving treatment option in refractory focal epilepsy. Due to poor visualization of ANT in traditional MRI sequences used for movement disorder surgery, targeting of ANT is mainly based on stereotactic atlas information. Sophisticated 3T MRI methods enable visualization of ANT, but 1.5T MRI is still preferred or more readily available in a large number of centers performing DBS. OBJECTIVE: In the present study, we sought to determine whether ANT could be adequately visualized at 1.5T MRI pre- and postoperatively using imaging techniques similar to the ones visualizing ANT in 3T MRI. A total of 15 MRI examinations with short tau inversion recovery (STIR) and T1-weighted magnetization prepared gradient echo (MPRAGE) images were performed to visualize ANT in nonepileptic subjects (n = 2), patients with vagus nerve stimulator (VNS) (n = 3), stereotactic MRI (n = 3), patients with ANT-DBS (n = 7). RESULTS: ANT was distinctly visualized in STIR and T1-weighted MPRAGE images in patients without implanted stimulators, with Leksell stereotactic frame and with fully implanted VNS. Postoperative 1.5T MRI was able to demonstrate some of the anatomical landmarks around ANT enabling assessment of electrode contact locations. CONCLUSIONS: The visualization of ANT is possible in preoperative 1.5T MRI enabling direct targeting of ANT all examined situations. The use of indirect targeting and its inherent potential for lead misplacement due to anatomical variation may be avoided using these MRI methods. Furthermore, postoperative MRI with STIR and T1-weighted MPRAGE images enable detailed postoperative assessment of contact locations. PMID- 27398712 TI - Advanced Evaluation of the Long-Term Stability of Oxygen Evolution Electrocatalysts. AB - Evaluation of the long-term stability of electrocatalysts is typically performed using galvanostatic polarization at a predefined current density. A stable or insignificant increase in the applied potential is usually interpreted as high long-term stability of the tested catalyst. However, effects such as (i) electrochemical degradation of a catalyst due to its oxidation, (ii) blocking of the catalyst surface by evolved gas bubbles, and (iii) detachment of the catalyst from the electrode surface may lead to a decrease of the catalyst's active surface area being exposed to the electrolyte. In order to separate these effects and to evaluate the true electrochemical degradation of electrocatalysts, an advanced evaluation protocol based on subsequently performed electrochemical impedance, double layer capacitance, cyclic voltammetry, and galvanostatic polarization measurements was developed and used to evaluate the degradation of IrO2 particles drop-coated on glassy carbon rotating disk electrode using Nafion as a binder. A flow-through electrochemical cell was developed enabling circulation of the electrolyte leading to an efficient removal of evolved oxygen bubbles even at high current densities of up to 250 mA/cm(2). The degradation rate of IrO2 was evaluated over 225 test cycles (0.733 +/- 0.022 mV/h) with a total duration of galvanostatic polarization measurements of over 55 h. PMID- 27398713 TI - Molecular Dynamics Simulation of the Crystal Nucleation and Growth Behavior of Methane Hydrate in the Presence of the Surface and Nanopores of Porous Sediment. AB - The behavior of hydrate formation in porous sediment has been widely studied because of its importance in the investigation of reservoirs and in the drilling of natural gas hydrate. However, it is difficult to understand the hydrate nucleation and growth mechanism on the surface and in the nanopores of porous media by experimental and numerical simulation methods. In this work, molecular dynamics simulations of the nucleation and growth of CH4 hydrate in the presence of the surface and nanopores of clay are carried out. The molecular configurations and microstructure properties are analyzed for systems containing one H2O hydrate layer (System A), three H2O hydrate layers (System B), and six H2O hydrate layers (System C) in both clay and the bulk solution. It is found that hydrate formation is more complex in porous media than in the pure bulk solution and that there is cooperativity between hydrate growth and molecular diffusion in clay nanopores. The hydroxylated edge sites of the clay surface could serve as a source of CH4 molecules to facilitate hydrate nucleation. The diffusion velocity of molecules is influenced by the growth of the hydrate that forms a block in the throats of the clay nanopore. Comparing hydrate growth in different clay pore sizes reveals that the pore size plays an important role in hydrate growth and molecular diffusion in clay. This simulation study provides the microscopic mechanism of hydrate nucleation and growth in porous media, which can be favorable for the investigation of the formation of natural gas hydrate in sediments. PMID- 27398714 TI - Combined Experimental and Molecular Simulation Investigation of the Individual Effects of Corexit Surfactants on the Aerosolization of Oil Spill Matter. AB - We report laboratory aerosolization experiments and classical molecular dynamics (MD) simulations, with the objective of investigating the individual effects of the two Corexit surfactants Span 80 (nonionic) and dioctyl sodium sulfosuccinate (DOSS, ionic), on the aerosolization of oil spill matter to the atmosphere. Our simulation results show that Span 80, DOSS, and the oil alkanes n-pentadecane (C15) and n-triacontane (C30) exhibit deep free energy minima at the air/seawater interface. C15 and C30 exhibit deeper free energy minima at the interface when Span 80 is present, as compared to the situation when DOSS or no surfactants are at the interface. These results suggest that Span 80 makes these oil hydrocarbons more likely to be adsorbed at the surface of seawater droplets and carried out to the atmosphere, relative to DOSS or to the situation where no surfactants are present. These simulation trends are in qualitative agreement with our experimental observations in a bubble-column setup, where larger amounts of oil hydrocarbons are ejected when Span 80 is mixed with oil and injected into the column, as compared to when DOSS is used. Our simulations also indicate that Span 80 has a larger thermodynamic incentive than DOSS to move from the seawater phase and into the air/seawater interface. This observation is also in qualitative agreement with our experimental measurements, which indicate that Span 80 is ejected in larger quantities than DOSS. Our simulations also suggest that DOSS predominantly adopts a perpendicular orientation with respect to the air/seawater interface at a dispersant to oil ratio (DOR) of 1:20, but has a slight preference to lie parallel to the interfaces at a DOR = 1:5; in both cases, DOSS molecules have their tails wide open and stretched. In contrast, Span 80 has a slight preference to align parallel to the interfaces with a coiled conformation at both DOR values. PMID- 27398715 TI - From Widely Accepted Concepts in Coordination Chemistry to Inverted Ligand Fields. AB - We begin with a brief historical review of the development of our understanding of the normal ordering of nd orbitals of a transition metal interacting with ligands, the most common cases being three below two in an octahedral environment, two below three in tetrahedral coordination, and four below one in a square-planar environment. From the molecular orbital construction of these ligand field splittings evolves a strategy for inverting the normal order: the obvious way to achieve this is to raise the ligand levels above the metal d's; that is, make the ligands better Lewis bases. However, things are not so simple, for such metal/ligand level placement may lead to redox processes. For 18 electron octahedral complexes one can create the inverted situation, but it manifests itself in the makeup of valence orbitals (are they mainly on metal or ligands?) rather than energy. One can also see the effect, in small ways, in tetrahedral Zn(II) complexes. We construct several examples of inverted ligand field systems with a hypothetical but not unrealistic AlCH3 ligand and sketch the consequences of inversion on reactivity. Special attention is paid to the square planar case, exemplified by [Cu(CF3)4](-), in which Snyder had the foresight to see a case of an inverted field, with the empty valence orbital being primarily ligand centered, the dx2-y2 orbital heavily occupied, in what would normally be called a Cu(III) complex. For [Cu(CF3)4](-) we provide theoretical evidence from electron distributions, geometry of the ligands, thermochemistry of molecule formation, and the energetics of abstraction of a CF3 ligand by a base, all consistent with oxidation of the ligands in this molecule. In [Cu(CF3)4](-), and perhaps more complexes on the right side of the transition series than one has imagined, some ligands are sigma-noninnocent. Exploration of inverted ligand fields helps us see the continuous, borderless transition from transition metal to main group bonding. We also give voice to a friendly disagreement on oxidation states in these remarkable molecules. PMID- 27398716 TI - Kinetic Resolution of Oxaziridines via Chiral Bifunctional Guanidine-Catalyzed Enantioselective alpha-Hydroxylation of beta-Keto Esters. AB - An efficient kinetic resolution of racemic oxaziridines has been realized via catalytic asymmetric alpha-hydroxylation of available beta-keto esters. In the presence of a chiral bifunctional guanidine catalyst, a variety of optically active oxaziridines and chiral alpha-hydroxy beta-keto esters were generated with excellent results (ee's of up to 99% and 97% and yields of up to 44% and 54%, respectively). PMID- 27398717 TI - Phenanthrylene-butadiynylene and Phenanthrylene-thienylene Macrocycles: Synthesis, Structure, and Properties. AB - A series of macrocycles consisting of 9,10-substituted phenanthrenes connected by butadiynylene linkers in positions 3 and 6 has been described as well as their transformation into the corresponding phenanthrylene-thienylene macrocycles. Structure and properties of the macrocycles, such as self-association in solution and optical and electrochemical properties, were studied and reported in a comparative manner with respect to the effects of the different sizes and shapes of the macrocycles and the character and length of their side chains. PMID- 27398718 TI - Super-Resolution Imaging of a Dielectric Microsphere Is Governed by the Waist of Its Photonic Nanojet. AB - Dielectric microspheres with appropriate refractive index can image objects with super-resolution, that is, with a precision well beyond the classical diffraction limit. A microsphere is also known to generate upon illumination a photonic nanojet, which is a scattered beam of light with a high-intensity main lobe and very narrow waist. Here, we report a systematic study of the imaging of water immersed nanostructures by barium titanate glass microspheres of different size. A numerical study of the light propagation through a microsphere points out the light focusing capability of microspheres of different size and the waist of their photonic nanojet. The former correlates to the magnification factor of the virtual images obtained from linear test nanostructures, the biggest magnification being obtained with microspheres of ~6-7 MUm in size. Analyzing the light intensity distribution of microscopy images allows determining analytically the point spread function of the optical system and thereby quantifies its resolution. We find that the super-resolution imaging of a microsphere is dependent on the waist of its photonic nanojet, the best resolution being obtained with a 6 MUm O microsphere, which generates the nanojet with the minimum waist. This comparison allows elucidating the super-resolution imaging mechanism. PMID- 27398719 TI - Dynamic Bcl-xL (S49) and (S62) Phosphorylation/Dephosphorylation during Mitosis Prevents Chromosome Instability and Aneuploidy in Normal Human Diploid Fibroblasts. AB - Bcl-xL proteins undergo dynamic phosphorylation/dephosphorylation on Ser49 and Ser62 residues during mitosis. The expression of Bcl-xL(S49A), (S62A) and dual (S49/62A) phosphorylation mutants in tumor cells lead to severe mitotic defects associated with multipolar spindle, chromosome lagging and bridging, and micro-, bi- and multi-nucleated cells. Because the above observations were made in tumor cells which already display genomic instability, we now address the question: will similar effects occur in normal human diploid cells? We studied normal human diploid BJ foreskin fibroblast cells expressing Bcl-xL (wild type), (S49A), (S49D), (S62A), (S62D) and the dual-site (S49/62A) and (S49/62D) mutants. Cells expressing S49 and/or S62 phosphorylation mutants showed reduced kinetics of cell population doubling. These effects on cell population doubling kinetics correlated with early outbreak of senescence with no impact on the cell death rate. Senescent cells displayed typical senescence-associated phenotypes including high-level of senescence-associated beta-galactosidase activity, interleukin-6 (IL-6) secretion, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21Waf1/Cip1 activation as well as gammaH2A.X-associated nuclear chromatin foci. Fluorescence in situ hybridization analysis and Giemsa-banded karyotypes revealed that the expression of Bcl-xL phosphorylation mutants in normal diploid BJ cells provoked chromosome instability and aneuploidy. These findings suggest that dynamic Bcl-xL(S49) and (S62) phosphorylation/dephosphorylation cycles are important in the maintenance of chromosome integrity during mitosis in normal cells. They could impact future strategies aiming to develop and identify compounds that could target not only the anti-apoptotic domain of Bcl-xL protein, but also its mitotic domain for cancer therapy. PMID- 27398720 TI - Exenatide Treatment Alone Improves beta-Cell Function in a Canine Model of Pre Diabetes. AB - BACKGROUND: Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. OBJECTIVE: We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. DESIGN AND METHODS: After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks. beta-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG), the oral glucose tolerance test (OGTT, insulinogenic index) and the graded-hyperglycemic clamp (clamp insulinogenic index). Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess beta-cell function in vitro. RESULTS: OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5%) (P = 0.011). IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9%) (P = 0.002). AIRG decreased by 54.0% (IQR, 40.7%) (P = 0.010), leading to mild fasting hyperglycemia (P = 0.039). Exenatide, compared with placebo, decreased body weight (P<0.001) without altering food intake, fasting glycemia, insulinemia, glycated hemoglobin A1c, or glucose tolerance. Exenatide, compared with placebo, increased both OGTT- (P = 0.040) and clamp-based insulinogenic indexes (P = 0.016), improved insulin secretion in vitro (P = 0.041), but had no noticeable effect on insulin sensitivity (P = 0.405). CONCLUSIONS: In pre-diabetic canines, 12-week exenatide treatment improved beta-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes. PMID- 27398722 TI - Assessing the stability of alanine-based helices by conformer-selective IR spectroscopy. AB - Polyalanine based peptides that carry a lysine at the C-terminus ([Ac-AlanLys + H](+)) are known to form alpha-helices in the gas phase. Three factors contribute to the stability of these helices: (i) the interaction between the helix macro dipole and the charge, (ii) the capping of dangling C[double bond, length as m dash]O groups by lysine and (iii) the cooperative hydrogen bond network. In previous studies, the influence of the interaction between the helix dipole and the charge as well as the impact of the capping was studied intensively. Here, we complement these findings by systematically assessing the third parameter, the H bond network. In order to selectively remove one H-bond along the backbone, we use amide-to-ester substitutions. The resulting depsi peptides were analyzed by ion-mobility and m/z-selective infrared spectroscopy as well as theoretical calculations. Our results indicate that peptides which contain only one ester bond still maintain the helical conformation. We conclude that the interaction between the charge and the helix macro-dipole is most crucial for the formation of the alpha-helical conformation and a single backbone H-bond has only little influence on the overall stability. PMID- 27398721 TI - Limited Contribution of DNA Methylation Variation to Expression Regulation in Arabidopsis thaliana. AB - The extent to which epigenetic variation affects complex traits in natural populations is not known. We addressed this question using transcriptome and DNA methylation data from a sample of 135 sequenced A. thaliana accessions. Across individuals, expression was significantly associated with cis-methylation for hundreds of genes, and many of these associations remained significant after taking SNP effects into account. The pattern of correlations differed markedly between gene body methylation and transposable element methylation. The former was usually positively correlated with expression, and the latter usually negatively correlated, although exceptions were found in both cases. Finally, we developed graphical models of causality that adapt to a sample with heavy population structure, and used them to show that while methylation appears to affect gene expression more often than expression affects methylation, there is also strong support for both being independently controlled. In conclusion, although we find clear evidence for epigenetic regulation, both the number of loci affected and the magnitude of the effects appear to be small compared to the effect of SNPs. PMID- 27398723 TI - An ultra-fast illuminating fluorescent probe for monitoring formaldehyde in living cells, shiitake mushrooms, and indoors. AB - An ultra-fast illuminating fluorescent formaldehyde (FA) probe (R6-FA) was designed and synthesized, and it exhibited a significant response to both FA in aqueous solution and as a gas. We have employed R6-FA not only to image FA in living cells, but also to detect FA in dried shiitake mushrooms and indoors for the first time, indicating its broad potential applications for monitoring FA in living systems, the food industry, and the environment. PMID- 27398726 TI - Extended Adaptive Biasing Force Algorithm. An On-the-Fly Implementation for Accurate Free-Energy Calculations. AB - Proper use of the adaptive biasing force (ABF) algorithm in free-energy calculations needs certain prerequisites to be met, namely, that the Jacobian for the metric transformation and its first derivative be available and the coarse variables be independent and fully decoupled from any holonomic constraint or geometric restraint, thereby limiting singularly the field of application of the approach. The extended ABF (eABF) algorithm circumvents these intrinsic limitations by applying the time-dependent bias onto a fictitious particle coupled to the coarse variable of interest by means of a stiff spring. However, with the current implementation of eABF in the popular molecular dynamics engine NAMD, a trajectory-based post-treatment is necessary to derive the underlying free-energy change. Usually, such a posthoc analysis leads to a decrease in the reliability of the free-energy estimates due to the inevitable loss of information, as well as to a drop in efficiency, which stems from substantial read-write accesses to file systems. We have developed a user-friendly, on-the fly code for performing eABF simulations within NAMD. In the present contribution, this code is probed in eight illustrative examples. The performance of the algorithm is compared with traditional ABF, on the one hand, and the original eABF implementation combined with a posthoc analysis, on the other hand. Our results indicate that the on-the-fly eABF algorithm (i) supplies the correct free-energy landscape in those critical cases where the coarse variables at play are coupled to either each other or to geometric restraints or holonomic constraints, (ii) greatly improves the reliability of the free-energy change, compared to the outcome of a posthoc analysis, and (iii) represents a negligible additional computational effort compared to regular ABF. Moreover, in the proposed implementation, guidelines for choosing two parameters of the eABF algorithm, namely the stiffness of the spring and the mass of the fictitious particles, are proposed. The present on-the-fly eABF implementation can be viewed as the second generation of the ABF algorithm, expected to be widely utilized in the theoretical investigation of recognition and association phenomena relevant to physics, chemistry, and biology. PMID- 27398725 TI - Bioaccumulation of Multiwall Carbon Nanotubes in Tetrahymena thermophila by Direct Feeding or Trophic Transfer. AB - Consumer goods contain multiwall carbon nanotubes (MWCNTs) that could be released during product life cycles into the environment, where their effects are uncertain. Here, we assessed MWCNT bioaccumulation in the protozoan Tetrahymena thermophila via trophic transfer from bacterial prey (Pseudomonas aeruginosa) versus direct uptake from growth media. The experiments were conducted using (14)C-labeled MWCNT ((14)C-MWCNT) doses at or below 1 mg/L, which proved subtoxic since there were no adverse effects on the growth of the test organisms. A novel contribution of this study was the demonstration of the ability to quantify MWCNT bioaccumulation at low (sub MUg/kg) concentrations accomplished by employing accelerator mass spectrometry (AMS). After the treatments with MWCNTs at nominal concentrations of 0.01 mg/L and 1 mg/L, P. aeruginosa adsorbed considerable amounts of MWCNTs: (0.18 +/- 0.04) MUg/mg and (21.9 +/- 4.2) MUg/mg bacterial dry mass, respectively. At the administered MWCNT dose of 0.3 mg/L, T. thermophila accumulated up to (0.86 +/- 0.3) MUg/mg and (3.4 +/- 1.1) MUg/mg dry mass by trophic transfer and direct uptake, respectively. Although MWCNTs did not biomagnify in the microbial food chain, MWCNTs bioaccumulated in the protozoan populations regardless of the feeding regime, which could make MWCNTs bioavailable for organisms at higher trophic levels. PMID- 27398727 TI - Modified Numerical Simulation Model of Blood Flow in Bend. AB - The numerical simulation model of blood flow in bend is studied in this paper. The curvature modification is conducted for the blood flow model in bend to obtain the modified blood flow model in bend. The modified model is verified by U tube. By comparing the simulation results with the experimental results obtained by measuring the flow data in U tube, it was found that the modified blood flow model in bend can effectively improve the prediction accuracy of blood flow data affected by the curvature effect. PMID- 27398728 TI - Intravascular large B-cell lymphoma with a high titer of proteinase-3-anti neutrophil cytoplasmic antibody mimicking granulomatosis with polyangiitis. AB - A 63-year-old man presented with fever, sinusitis, otitis, and high titers of proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA). Granulomatosis with polyangiitis (GPA) was first suspected. However, nasal mucosa and skin biopsies revealed the presence of intravascular large B-cell lymphoma (IVLBCL). We present a rare case of IVLBCL with a high titer of PR3-ANCA mimicking GPA. PMID- 27398729 TI - A systematic evaluation for the potential translation of CD166-related expression as a cancer biomarker. AB - INTRODUCTION: Many basic studies have provided some evidences for the correlations of CD166 to cancer. However, along with the growing studies on the clinical values of CD166 in cancer areas, some controversial and inconclusive results were obtained. AREAS COVERED: An appropriate query and collection of the published articles was conducted through search in PubMed and EMBASE database. A subsequent systematical and quantitative summary of CD166 related expression and cancer was conducted with meta-analysis to clarify its clinical significance for potential translation as cancer biomarkers. Expert commentary: The overall results suggested total CD166 correlated to cancer risk, membrane CD166 correlated to nodal metastasis and cytoplasmic CD166 correlated to TNM stage, and disease-free survival. The membrane CD166, cytoplasmic CD166 and soluble CD166 showed great potential to be used as a panel of markers for predicting cancer overall survival. We might conclude that CD166 functions as a risk factor for cancers, and the alterations of its different functional isoforms were observed to correlate with specific or interplayed clinical outcomes. PMID- 27398730 TI - Increased self-reported impulsivity in methamphetamine users maintaining drug abstinence. AB - BACKGROUND: Impulsivity has been proposed as an important factor in the initiation and maintenance of addiction. Indirect evidence suggests that some methamphetamine users report less impulsivity when they are using methamphetamine compared to when abstaining from drug use, but this hypothesis has not been directly tested. OBJECTIVES/METHODS: In this study, self-reports of impulsivity were obtained from 32 methamphetamine-dependent (DSM-IV) research participants and 41 healthy control subjects, using the Barratt Impulsiveness Scale-11. The methamphetamine users were assessed during an active period of methamphetamine use, as determined through urinalysis, and again after approximately 1 week of confirmed abstinence. Control subjects likewise completed two assessments. A subset of participants also completed serial assessments of the Beck Depression Inventory (Methamphetamine Group, N = 17, Control Group, N = 38) and the Methamphetamine Withdrawal Questionnaire (Methamphetamine Group, N = 12). RESULTS: There was a significant interaction of group with time on impulsivity (p = 0.044), reflecting a significant increase from the first to the second assessment in the methamphetamine users (p = 0.013), but no change among healthy control subjects. In contrast, depressive and withdrawal symptoms significantly decreased between the first and second assessments in the methamphetamine users (ps <=0.01). Change in impulsivity in methamphetamine users was not significantly correlated with change in withdrawal or depression (ps >0.05). CONCLUSIONS: These findings suggest that methamphetamine users report more impulsivity when abstaining from drug use, an effect that is not significantly related to methamphetamine withdrawal. Attenuation of impulsivity may reinforce continued methamphetamine use in these individuals. PMID- 27398732 TI - ABSTRACTS 7th World Congress of Mountain & Wilderness Medicine A combined meeting of the International Society for Mountain Medicine and the Wilderness Medical Society July 30-August 4, 2016 Telluride, Colorado. PMID- 27398731 TI - YaAn earthquake increases blood pressure among hospitalized patients. AB - BACKGROUND: YaAn, a city in Sichuan province, China, was struck by a major earthquake measuring 7.0 on the Richter scale on April 20, 2013. This study sought to investigate the impact of YaAn earthquake on the blood pressure (BP) among hospitalized patients in the department of cardiology. METHODS: We enrolled 52 hospitalized patients who were admitted to our hospital at least three days before the day of earthquake in 2013 (disaster group) as compared with 52 patients during April 20, 2014 (nondisaster group). BP was measured three times per day and the prescription of antihypertensive medicine was recorded. RESULTS: The earthquake induced a 3.3 mm Hg significant increase in the mean postdisaster systolic blood pressure (SBP) in the disaster group as compared with the nondisaster group. SBP at admission was positively associated with the elevated SBP in the logistic regression model (odds ratio (OR) = 1.09, 95% confidence interval (CI):1.016-1.168, p = 0.015), but not other potential influencing factors, including antihypertensive medicine, sex, age, and body weight, excluding beta-blockers. Patients with beta-blockers prescription at the time of earthquake showed a blunt response to earthquake-induced SBP elevation than those who were taking other antihypertensive drugs (OR = 0.128, 95% CI: 0.019-0.876, p = 0.036). CONCLUSION: The YaAn earthquake induced significant increase in SBP even at a distance from the epicenter among hospitalized patients. The findings demonstrate that pure psychological components seem to be a cause of the pressor response and beta-blockers might be better in controlling disaster-induced hypertension. PMID- 27398733 TI - Understanding the Value of Both Laparoscopic and Robotic Approaches Compared to the Open Approach in Colorectal Surgery. AB - INTRO: Although the use of laparoscopy has significantly increased in colorectal procedures, robotic surgery may enable additional cases to be performed using a minimally invasive approach. We separately evaluated the value of laparoscopic and robotic colorectal procedures compared to the open approach. METHODS: Patients undergoing nonemergent colorectal operations from 2010 to 2013 with National Surgical Quality Improvement Project data were identified. Robotic and laparoscopic procedures were separately matched (1:1) to open cases. Outcomes included 30-day composite morbidity, length of stay, operative time, and inpatient costs. Frequently used intraoperative disposable items were categorized, and significant cost contributors were identified by surgical approach. Statistical differences were determined with Chi-square and Wilcoxon signed-rank tests. RESULTS: Both laparoscopic (n = 67) and robotic (n = 45) approaches were associated with decreased composite morbidity compared to matched open cases (lap vs. open: 22.4% vs. 49.2%, P < .01; robotic vs. open: 6.7% vs. 33.3%, P < .01). Median length of stay was significantly shorter for both laparoscopic and robotic compared to open surgery (lap vs. open: 5 vs. 7 days, P < .01; robotic vs. open: 5 vs. 7 days, P < .01). Median hospital costs were similar between laparoscopic and open surgery ($13,319 vs. $14,039; P = .80) and robotic and open surgery ($13,778 vs. $13,629; P = .48). CONCLUSION: These findings illustrate the value for both laparoscopic and robotic approaches to colorectal surgery compared to the open approach in terms of short-term outcomes and inpatient costs. Advanced intraoperative disposable items such as cutting staplers and energy devices are important targets for additional cost containment. PMID- 27398735 TI - Polyetheretherketone/poly (glycolic acid) blend scaffolds with biodegradable properties. AB - Polyetheretherketone (PEEK) is widely applied in tissue engineering due to its good biocompatibility and mechanical properties. However, the slow degradation rate limits its further application. In this study, PEEK blended with plyglycolicacid (PGA) was used to fabricate porous scaffolds via selective laser sintering. The results demonstrated that the blend scaffolds could gradually degrade, and the degradation rate was able to regulate by tailoring the PGA content. Moreover, the scaffolds maintained good biocompatibility and suitable mechanical properties. These were explained as follows: PGA on the surface layer of the scaffolds might degrade first owing to its exposure to the ambient medium. The degraded PGA left much space, which could promote cell attachment and proliferation. Meanwhile, the slow degradation of PEEK was beneficial to sustaining the scaffolds' strength and stable structure. PMID- 27398734 TI - Interactions of hyperhomocysteinemia and T cell immunity in causation of hypertension. AB - Although hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVD), there is a debate on whether HHcy is a risk factor or just a biomarker. Interestingly, homocysteine lowering strategies in humans had very little effect on reducing the cardiovascular risk, as compared with animals; this may suggest heterogeneity in human population and epigenetic alterations. Moreover, there are only few studies that suggest the idea that HHcy contributes to CVD in the presence of other risk factors such as inflammation, a known risk factor for CVD. Elevated levels of homocysteine have been shown to contribute to inflammation. Here, we highlight possible relationships between homocysteine, T cell immunity, and hypertension, and summarize the evidence that suggested these factors act together in increasing the risk for CVD. In light of this new evidence, we further propose that there is a need for evaluation of the causes of HHcy, defective remethylation or defective transsulfuration, which may differentially modulate hypertension progression, not just the homocysteine levels. PMID- 27398736 TI - Reduction of quality of life in prostate cancer patients: experience among 6200 men in the Nordic countries. AB - OBJECTIVE: Although many studies have dealt with adverse effects (AEs) and quality of life (QoL) in prostate cancer (PCa) patients, the quantification of the patients' perspective on AE-related reduction in QoL has been less studied. This study describes the impact of self-reported local (erectile, bowel, urinary dysfunction) or systemic (mental distress, fatigue, virility loss) AEs on QoL reduction. MATERIALS AND METHODS: Nordic PCa patients completed a questionnaire containing 84 multiple-choice questions. The main outcome variable of the survey was patient-reported PCa-induced QoL reduction, assessed by descriptive and regression analyses. The level of significance was p < 0.05. RESULTS: Among 6200 patients, 39% described their QoL as reduced owing to the PCa trajectory: radical prostatectomy group (RPGroup): 42%, radiotherapy without hormones (RADGroup): 27%, hormones (HormGroup): 47% and no treatment (NoTrtGroup): 19%. Except for the NoTrtGroup, urinary leakage and fatigue doubled the risk of QoL reduction, while virility loss and erectile dysfunction tripled the risk. Significant intergroup differences emerged for the age-adjusted odds of QoL reduction: RPGroup (0.66), RADGroup (0.40), HormGroup (0.95) and NoTrtGroup (0.22). CONCLUSIONS: After RP, RAD or hormone treatment of PCa, systemic AEs, in particular loss of virility, significantly reduce PCa patients' QoL similarly to or more than local AEs. The probability of reduced QoL is highest during hormone treatment and lowest in patients without anticancer therapy, and seems lower in patients treated with RAD without hormones than after RP. The treatment-related risk of reduced QoL due to systemic AEs should become a part of the pretreatment counselling of patients. PMID- 27398737 TI - Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis. AB - Septic shock is a major cause of death worldwide and a considerable healthcare burden in the twenty-first century. Attention has shifted from damaging effects of the proinflammatory response to the detrimental role of antiinflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to reevaluate the current management of septic shock and to assess whether we are inadvertently compromising or altering the host immune response. In this perspective, we discuss the potential detrimental role of norepinephrine, the cornerstone treatment for septic shock, in sepsis-induced immunoparalysis. We provide a short overview of the current understanding of the immunologic pathophysiology of sepsis, followed by a detailed description of the immunomodulatory effects of norepinephrine and alternative vasopressors. We conclude that although the development of novel therapies aimed at reversing immunoparalysis is underway, the use of norepinephrine may aggravate the development, extent, and duration of sepsis-induced immunoparalysis. Current in vitro and animal data indicate that norepinephrine treatment exerts immunosuppressive and bacterial growth-promoting effects and may increase susceptibility toward infections. However, evidence in humans is circumstantial, as immunologic effects of norepinephrine have not been investigated properly in experimental or clinical studies. Alternatives such as vasopressin/selepressin, angiotensin II, and phenylephrine could have a fundamental advantage over norepinephrine with respect to their immunologic properties. However, also for these agents, in vivo immunologic data in humans are largely lacking. As such, human studies on the immunomodulatory properties of norepinephrine and viable alternatives are highly warranted. PMID- 27398738 TI - Superhydrophobic, Hybrid, Electrospun Cellulose Acetate Nanofibrous Mats for Oil/Water Separation by Tailored Surface Modification. AB - Electrospun cellulose acetate nanofibers (CA-NF) have been modified with perfluoro alkoxysilanes (FS/CA-NF) for tailoring their chemical and physical features aiming oil-water separation purposes. Strikingly, hybrid FS/CA-NF showed that perfluoro groups are rigidly positioned on the outer surface of the nanofibers providing superhydrophobic characteristic with a water contact angle of ~155 degrees . Detailed analysis showed that hydrolysis/condensation reactions led to the modification of the acetylated beta(1 -> 4) linked d-glucose chains of CA transforming it into a superhydrophobic nanofibrous mat. Analytical data have revealed that CA-NF surfaces can be selectively controlled for fabricating the durable, robust and water resistant hybrid electrospun nanofibrous mat. The -OH groups available on the CA structure allowed the basic sol-gel reactions started by the reactive FS hybrid precursor system which can be monitored by spectroscopic analysis. Since alkoxysilane groups on the perfluoro silane compound are capable of reacting for condensation together with the CA, superhydrophobic nanofibrous mat is obtained via electrospinning. This structural modification led to the facile fabrication of the novel oil/water nanofibrous separator which functions effectively demonstrated by hexane/oil and water separation experiments. Perfluoro groups consequently modified the hydrophilic CA nanofibers into superhydrophobic character and therefore FS/CA-NF could be quite practical for future applications like water/oil separators, as well as self cleaning or water resistant nanofibrous structures. PMID- 27398739 TI - Unilateral superior condylar neck fracture with dislocation in a child treated with an acrylic splint in the upper arch for functional repositioning of the mandible. AB - BACKGROUND: To present the outcomes for a case of unilateral mandibular subcondylar fracture with dislocation in an 11-year-old female treated with an acrylic splint for functional repositioning of the mandible. CLINICAL PRESENTATION: A splint was placed in the upper arch to restore the functional repositioning of the mandible. The splint's height was increased up to 5.5 mm on the side of the fracture to stimulate growth on the deficient side. To correct the mandibular asymmetry, a construction bite was made by 4 mm advancing. The total treatment time was 16 months. Long-term five-year follow up showed complete healing. A portion of the ramus appeared lateral with respect to the condylar head, whereas the mandibular deviation to the right side was fully corrected. CONCLUSION: Conservative treatment may be an appropriate method for children in select cases, as they have an increased potential for spontaneous regeneration. PMID- 27398740 TI - Efficacy of lenvatinib in treating thyroid cancer. AB - INTRODUCTION: Radioiodine [RAI]-resistant advanced and progressive differentiated thyroid cancer [DTC], although rare, constitutes a real challenge as its prognosis is poor and available therapeutic options, until now, have been limited. Discovery of a crucial role of distinct tyrosine kinases in DTC pathogenesis opened up new options in systemic treatment. Lenvatinib is an oral potent multi kinase inhibitor [MKI] of different growth factor receptors including VEGFR1/Flt-1, VEGFR2/KDR, VEGFR3, FGFR1,2,3,4, PDGFR-beta as well as RET and KIT signaling networks. Its activity against RAI-refractory DTC was demonstrated in clinical studies fulfilling evidence-based medicine [EBM] criteria. The drug showed acceptable tolerance and manageable toxicity. AREAS COVERED: published results of phase II and III studies and other reports evaluated the efficacy and safety of lenvatinib in DTC and in medullary thyroid carcinoma. EXPERT OPINION: Currently there are two different MKIs, lenvatinib and sorafenib, which have demonstrated effectiveness against RAI-refractory DTC. However, to date, the question of which drug should be chosen for first line treatment remains open. The other question: when to start the treatment seems to be no less important. Whether disease progression, even by RECIST, is enough to initiate a therapy or tumor burden also plays an important role? EBM study, to resolve these issues, is our task for the nearest future. PMID- 27398741 TI - What do we know about the cost-effectiveness of pneumococcal conjugate vaccination in older adults? AB - The cost-effectiveness of 13-type pneumococcal conjugate vaccine (PCV13) use in older adults, and the relative merits when compared to the 23-type polysaccharide pneumococcal vaccine (PPV23), has been a topic of much debate. Although a number of economics evaluations have been conducted many of these were completed before the availability of critical data on PCV13 efficacy in older adults. Recent studies using this data have found conflicting results. This may in part reflect differences in the level of herd protection from infant pneumococcal vaccination programs in different countries. The costs and benefits of pneumococcal vaccination in adults are likely to rest on several critical parameters: the magnitude pneumococcal disease in older adults and the serotypes responsible for it, the efficacy of each vaccine against invasive and non-invasive pneumonia, the duration of vaccine protection, and differences in vaccine price. The ongoing changes in pneumococcal disease patterns highlight the need for economic evaluations to use recent serotype-specific disease estimates from the setting under consideration. In countries that do recommend PCV13 use in adults, post implementation economic evaluation (using data from after a program is implemented) may be useful to help inform potential future changes to vaccine recommendations as well as the maximum price that should be paid for the vaccines in future negotiations. PMID- 27398742 TI - Replication Protein A (RPA) deficiency activates the Fanconi anemia DNA repair pathway. AB - The Fanconi anemia (FA) pathway regulates DNA inter-strand crosslink (ICL) repair. Despite our greater understanding of the role of FA in ICL repair, its function in the preventing spontaneous genome instability is not well understood. Here, we show that depletion of replication protein A (RPA) activates the FA pathway. RPA1 deficiency increases chromatin recruitment of FA core complex, leading to FANCD2 monoubiquitination (FANCD2-Ub) and foci formation in the absence of DNA damaging agents. Importantly, ATR depletion, but not ATM, abolished RPA1 depletion-induced FANCD2-Ub, suggesting that ATR activation mediated FANCD2-Ub. Interestingly, we found that depletion of hSSB1/2-INTS3, a single-stranded DNA-binding protein complex, induces FANCD2-Ub, like RPA1 depletion. More interestingly, depletion of either RPA1 or INTS3 caused increased accumulation of DNA damage in FA pathway deficient cell lines. Taken together, these results indicate that RPA deficiency induces activation of the FA pathway in an ATR-dependent manner, which may play a role in the genome maintenance. PMID- 27398743 TI - Dietary Patterns and Their Socioeconomic and Behavioral Determinants in 6- to 8 Year-Old Portuguese Children. AB - Adherence to a healthier diet is declining, with children consuming more saturated fats and simple carbohydrates. Factors influencing this choice were studied using a cross-sectional study with children (6 to 8 years old) living in Coimbra. Socioeconomic and behavioral factors were obtained from the parents. Dietary patterns of 1,063 children were identified: Mediterranean (MedDiet), saturated fats (SFatDiet), and base of Portuguese diet (BPDiet). Their relationship with socioeconomic and behavioral determinants was analyzed. SES determined strongly the dietary choices with lower SES being associated with higher consumption of SFatDiet and higher SES with BPDiet. Worse diet quality was shown to coexist with other unhealthy behaviors. PMID- 27398744 TI - Mating-Type Gene Structure and Spatial Distribution of Didymella tanaceti in Pyrethrum Fields. AB - Tan spot of pyrethrum (Tanacetum cinerariifolium) is caused by the ascomycete Didymella tanaceti. To assess the evolutionary role of ascospores in the assumed asexual species, the structure and arrangement of mating-type (MAT) genes were examined. A single MAT1-1 or MAT1-2 idiomorph was identified in all isolates examined, indicating that the species is heterothallic. The idiomorphs were flanked upstream and downstream by regions encoding pyridoxamine phosphate oxidase-like and DNA lyase-like proteins, respectively. A multiplex MAT-specific polymerase chain reaction assay was developed and used to genotype 325 isolates collected within two transects in each of four fields in Tasmania, Australia. The ratio of isolates of each mating-type in each transect was consistent with a 1:1 ratio. The spatial distribution of the isolates of the two mating-types within each transect was random for all except one transect for MAT1-1 isolates, indicating that clonal patterns of each mating-type were absent. However, evidence of a reduced selection pressure on MAT1-1 isolates was observed, with a second haplotype of the MAT1-1-1 gene identified in 4.4% of MAT1-1 isolates. In vitro crosses between isolates with opposite mating-types failed to produce ascospores. Although the sexual morph could not be induced, the occurrence of both mating-types in equal frequencies suggested that a cryptic sexual mode of reproduction may occur within field populations. PMID- 27398746 TI - Modelling the deflection of rowing oar shafts. AB - The deflection of rowing oar shafts subjected to a static load was investigated. Two sets of sculling oars of different design stiffness were tested at three different lengths from 2.66 to 2.70 m. Loads up to 201 N were applied to the blade end of the oar shafts, and deflections were measured at six positions along the length of the shafts. The experimental results were compared with theoretical predictions obtained by modelling the oar shafts as homogenous end-loaded cantilever beams. The results show that the oar shafts are not uniform, in contradiction to the assumed model, but rather are most compliant near the sleeves and up to 80% stiffer towards the blades. The effect of oar shaft stiffness and length on the deflection angle at the blade end of the oar shaft was at most 1.18 +/- 0.01 degrees . The measured variation of stiffness along the shaft has implications for boat propulsion and rowing performance. PMID- 27398748 TI - Letters. PMID- 27398747 TI - Editor's notes. PMID- 27398749 TI - Brief reports. PMID- 27398750 TI - Running wild. PMID- 27398751 TI - Sticking Your Neck Out. PMID- 27398752 TI - Benefits of Upper Extremity Exercise in Cardiac Rehabilitation. PMID- 27398753 TI - Benefits of Arm Exercise in Cardiac Rehabilitation. AB - Knowing the importance of arm exercise as well as leg exercise, and the physiological benefits of both, can aid the physician in designing a rehabilitation program for cardiac patients. PMID- 27398754 TI - Cme credit quiz no. 22. PMID- 27398755 TI - Are Athletic Trainers a Luxury or a Necessity? AB - Athletic trainers and physicians need to develop an understanding of how their complementary roles can provide comprehensive care for the injured athlete. PMID- 27398756 TI - The Effects of Officiating Football on Heart Rates. AB - Many people with sedentary jobs exercise strenuously on weekends. This report on a college football official shows what hidden dangers may lie in such sporadic activity. PMID- 27398757 TI - A System for Preventing Athletic Neck Injuries. AB - The risk of neck injury in football is high, and the consequences can be tragic. The authors present a simple, inexpensive method for preventing these injuries. PMID- 27398758 TI - Double Dislocation of the Finger: A Rare Occurrence. PMID- 27398759 TI - Olympic Training Centers: A New Concept for an Ancient Tradition. AB - The first United States Olympic Committee (USOC) Training Center opened without much fanfare at Squaw Valley, California, last summer, but it was viewed as the fulfillment of a long-held idea. At last, Olympic-bound US athletes could be trained under a coordinated program that pulled together the best training methods, augmented by scientific research and testing and a strong emphasis on sportsmedicine. Ali this was accepted with enthusiasm by the athletes and coaches who spent time at Squaw Valley, but there still are some formidable problems to be solved, and not everyone in the sportsmedicine community is happy with the planning. The Physician and Sportsmedicine talked with athletes, coaches, staff members, and observers to compile this report. PMID- 27398760 TI - Scanning sports. PMID- 27398761 TI - Fasting, Feasting, and Diabetes. PMID- 27398762 TI - Where are they now? PMID- 27398764 TI - Restoration of Dorsiflexion Following Distal Leg and Ankle Injuries. PMID- 27398766 TI - The Impact of a Woman's Dyspareunia and Its Treatment on Her Intimate Partner: A Qualitative Analysis. AB - This study explored the experiences of male partners of women with dyspareunia, secondary to provoked vestibulodynia (PVD), who participated in the Multidisciplinary Vulvodynia Program (MVP). Participants were 16 men between 22 and 45 years of age. Data were collected with semi-structured interviews and analyzed for themes. Men were interviewed about (a) the impact of the woman's PVD on themselves; and (b) the impact of the MVP on themselves. Participants experienced negative psychological effects (e.g., guilt) in addition to activating emotions (e.g., frustration). They reported diminished quantity and quality of sex. In the relationship, PVD caused strain, communication challenges, and possibilities for growth. The benefits, perceived by the partner, of the women participating in the treatment program included improvements in knowledge, communication, and psychological and sexual health. PMID- 27398767 TI - Sex Difference in Chronic Obstructive Lung Disease. Does it Matter? A Concise Review. AB - Chronic obstructive lung disease (COPD) primarily affects men; however, its epidemiology has been changing because more women have become smokers. Recently, investigators found that although women and men were exposed to the same amount of smoke fume, women tended to have more severe disease and higher mortality rate. They also complain of more dyspnoea and may experience more severe exacerbations than men. This led to the question of whether sex has an impact on COPD course and whether women have a higher susceptibility to smoke fumes than men. That may be explained by multiple complex factors highlighting the relationship between sex, epidemiology, method of diagnostics and the clinical course of the disease. In this review, sex differences in epidemiology, clinical presentation, exacerbation, co-morbidities and treatment are covered. PMID- 27398768 TI - Treatment of Acute HIV Infection and the Potential Role of Acutely HIV-Infected Persons in Cure Studies. AB - Diagnosis of acute HIV infection is important for accurate estimation of HIV incidence, identifying persons who are unaware of their HIV infection, and offering immediate treatment and risk-reduction strategies. The higher viral loads associated with acute HIV infection are associated with an increased risk of transmission. Current treatment recommendations are the same for acute and established infections. Studies of acute HIV infection indicate that initiation of antiretroviral therapy during this period may allow greater recovery of CD4+ T cell count and function and may result in a smaller latent viral reservoir and a skewing of infection away from central memory CD4+ T cells toward shorter-lived transitional memory CD4+ T cells. This article summarizes a presentation by Susan J. Little, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2015. PMID- 27398769 TI - Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy. AB - Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/uL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015. PMID- 27398770 TI - Management of Lipid Levels and Cardiovascular Disease in HIV-Infected Individuals: Just Give Them a Statin? AB - Current guidelines for managing cholesterol to reduce cardiovascular disease (CVD) risk focus on providing the appropriate intensity of statin therapy to reduce low-density lipoprotein cholesterol (LDL-C) level. There is very little evidence supporting the use of treatments aimed at raising high-density lipoprotein cholesterol level or reducing triglyceride levels. HIV-infected persons have excess risk of CVD compared with the general population. Statins are less effective at reducing LDL-C levels in HIV-infected persons who are also at greater risk for adverse effects from statin treatment. When selecting a statin to achieve desired lowering of LDL-C level, the potential for drug interactions with antiretroviral therapy must be considered. Information from ongoing research is expected to help identify optimal strategies for use of statin treatment in this population. This article summarizes a presentation by James H. Stein, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Chicago, Illinois, in May 201. PMID- 27398771 TI - Advance Care Planning and HIV Infection in the Era of Antiretroviral Therapy: A Review. AB - In the era of antiretroviral therapy, HIV infection has become a chronic illness with associated multimorbidity, and practitioners are faced with an emerging population of HIV-infected patients with evolving needs for advance care planning (ACP), defined as communication between individuals and their proxies to plan for future health care decisions. This article provides a review of original research studies on ACP in HIV-infected adults in the era of antiretroviral therapy (1996 present) from PubMed, EMBASE, and PsycINFO. Eleven studies conducted between 1996 and 2015 met the selection criteria, with study sizes ranging from 9 to 2864 participants. Most studies consisted of white men in outpatient settings and had poorly defined definitions of ACP. Prevalence of ACP was variable (36%-54% had end-of-life communication, 8%-47% had advance directives). Lack of ACP was most commonly associated with low income, followed by lower severity of illness, low education level, black or Hispanic race, female sex, younger age, injection drug use, and social isolation. Practitioners reported limited time or energy and inadequate preparation or training as barriers to ACP. Existing literature on ACP in the era of antiretroviral therapy is limited, but shows that ACP prevalence in HIV-infected individuals is variable depending on socioeconomic factors, severity of illness, and practitioner resources and training. More research is needed to increase ACP among HIV-infected individuals. PMID- 27398772 TI - Towards a Common Understanding of the Health Sciences. AB - OBJECTIVE: The aim of health sciences is to maintain and improve the health of individuals and populations and to limit disability. Health research has expanded astoundingly over the last century and a variety of scientific disciplines rooted in very different scientific and intellectual traditions has contributed to these goals. To allow health scientists to fully contextualize their work and engage in interdisciplinary research, a common understanding of the health sciences is needed. The aim of this paper is to respond to the call of the 1986 Ottawa Charter to improve health care by looking both within and beyond health and health care, and to use the opportunity offered by WHO's International Classification of Functioning, Disability and Health (ICF) for a universal operationalization of health, in order to develop a common understanding and conceptualization of the field of health sciences that account for its richness and vitality. METHODS: A critical analysis of health sciences based on WHO's ICF, on WHO's definition of health systems and on the content and methodological approaches promoted by the biological, clinical and socio-humanistic traditions engaged in health research. RESULTS: The field of health sciences is presented according to: 1) a specification of the content of the field in terms of people's health needs and the societal response to them, 2) a meta-level framework to exhaustively represent the range of mutually recognizable scientific disciplines engaged in health research and 3) a heuristic framework for the specification of a set of shared methodological approaches relevant across the range of these disciplines. CONCLUSION: This conceptualization of health sciences is offered to contextualize the work of health researchers, thereby fostering interdisciplinarity. PMID- 27398773 TI - High-Speed Microdialysis-Capillary Electrophoresis Assays for Measuring Branched Chain Amino Acid Uptake in 3T3-L1 cells. AB - We have developed a high-throughput microdialysis-capillary electrophoresis (MD CE) assay for monitoring branched chain amino acid (BCAA) uptake/release dynamics in 3T3-L1 cells. BCAAs (i.e., isoleucine, leucine, and valine) and their downstream metabolites (i.e., alanine, glutamine, and glutamate) are important indicators of adipocyte lipogenesis. To perform an analysis, amino acids were sampled using microdialysis, fluorescently labeled in an online reaction, separated using CE, and detected using laser-induced fluorescence (LIF) in a sheath flow cuvette. Separation conditions were optimized for the resolution of the BCAAs isoleucine, leucine, and valine, as well as 13 other amino acids, including ornithine, alanine, glutamine, and glutamate. CE separations were performed in <30 s, and the temporal resolution of the online MD-CE assay was <60 s. Limits of detection (LOD) were 400, 200, and 100 nM for isoleucine, leucine, and valine, respectively. MD-CE dramatically improved throughput in comparison to traditional offline CE methods, allowing 8 replicates of 15 samples (i.e., 120 analyses) to be assayed in <120 min. The MD-CE assay was used to assess the metabolism dynamics of 3T3-L1 cells over time, confirming the utility of the assay. PMID- 27398774 TI - Correlation between the Sorption-Induced Deformation of Nanoporous Glass and the Continuous Freezing of Adsorbed Argon. AB - In this article we study the dependence of the sorption-induced deformation of nanoporous glass on the liquid-solid phase transition of adsorbed argon. During cooling we observe a continuous reduction of the expansion of the porous glass matrix caused by the adsorbate. The contraction is attended by a likewise continuous change of the adsorbed argon's phase state from liquid to solid. This simultaneous behavior evidences that the liquid-solid phase transition leads to a reduction of the pressure the adsorbate exerts on the pore walls. Furthermore, the study shows that small temperature changes can temporarily cause strong deformations of the porous material that decay in long time intervals of up to 1 week. We expect that our observations for the model system of argon and porous glass can be generalized to other systems. Consequently, this study will have implications when considering porous materials for applications, e.g., as a medium for storage. PMID- 27398775 TI - Molecular Orbital Simulations of Metal 1s2p Resonant Inelastic X-ray Scattering. AB - For first-row transition metals, high-resolution 3d electronic structure information can be obtained using resonant inelastic X-ray scattering (RIXS). In the hard X-ray region, a K pre-edge (1s->3d) excitation can be followed by monitoring the dipole-allowed Kalpha (2p->1s) or Kbeta (3p->1s) emission, processes labeled 1s2p or 1s3p RIXS. Here the restricted active space (RAS) approach, which is a molecular orbital method, is used for the first time to study hard X-ray RIXS processes. This is achieved by including the two sets of core orbitals in different partitions of the active space. Transition intensities are calculated using both first- and second-order expansions of the wave vector, including, but not limited to, electric dipoles and quadrupoles. The accuracy of the approach is tested for 1s2p RIXS of iron hexacyanides [Fe(CN)6](n-) in ferrous and ferric oxidation states. RAS simulations accurately describe the multiplet structures and the role of 2p and 3d spin-orbit coupling on energies and selection rules. Compared to experiment, relative energies of the two [Fe(CN)6](3-) resonances deviate by 0.2 eV in both incident energy and energy transfer directions, and multiplet splittings in [Fe(CN)6](4-) are reproduced within 0.1 eV. These values are similar to what can be expected for valence excitations. The development opens the modeling of hard X-ray scattering processes for both solution catalysts and enzymatic systems. PMID- 27398777 TI - Isolated Surface Hydrides: Formation, Structure, and Reactivity. AB - Surface hydrides are ubiquitous in catalysis. However, their structures and properties are not as well-understood as those of their molecular counterparts, which have been extensively studied for the past 70 years. Hydrides isolated on surfaces have been characterized as stable entities on oxide surfaces or in zeolites. They have also been proposed as reaction intermediates in numerous catalytic processes (hydrogenation, hydrogenolysis, etc.). They have also been prepared via surface organometallic chemistry. In this review, we describe their key structural features and spectroscopic signatures. We discuss their reactivity and stability and also point out unexplored areas. PMID- 27398779 TI - Structure Tuning of Cationic Oligospermine-siRNA Conjugates for Carrier-Free Gene Silencing. AB - Oligospermine-siRNA conjugates are able to induce efficient luciferase gene silencing upon carrier-free transfection. These conjugates are readily accessible by a versatile automated chemistry that we developed using a DMT-spermine phosphoramidite reagent. In this article, we used this chemistry to study a wide range of structural modifications of the oligospermine-siRNA conjugates, i.e., variation of conjugate positions and introduction of chemical modifications to increase nuclease resistance. At first we examined gene silencing activity of a series of siRNA-tris(spermine) conjugates with and without chemical modifications in standard carrier assisted conditions. The three spermine units attached at one of the two ends of the sense strand or at the 3'-end of the antisense strand are compatible with gene silencing activity whereas attachment of spermine units at the 5'-end of the antisense strand abolished the activity. 2'-O-Methylated nucleotides introduced in the sense strand are compatible while not in the antisense strand. Thiophosphate links could be used without activity loss at the 3'-end of both strands and at the 5'-end of the sense strand to conjugate oligospermine. Consequently a series of oligospermine-siRNA conjugates containing 15 to 45 spermines units in various configurations were chosen, prepared, and examined in carrier-free conditions. Attachment of 30 spermine units singly at the 5'-end of the sense strand provides the most potent carrier-free siRNA. Longevity of luciferase gene silencing was studied using oligospermine-siRNA conjugates. Five day long efficiency with more than 80% gene expression knockdown was observed upon transfection without vector. Oligospermine-siRNA conjugates targeting cell-constitutive natural lamin A/C gene were prepared. Efficient gene silencing was observed upon carrier-free transfection of siRNA conjugates containing 20 or 30 spermine residues grafted at the 5'-end of the sense strand. PMID- 27398781 TI - A randomized controlled trial of brief interventions for problem gambling in substance abuse treatment patients. AB - OBJECTIVE: This study evaluated the efficacy of brief gambling treatments in patients attending substance abuse treatment clinics. METHOD: Substance abuse treatment patients with gambling problems (N = 217) were randomly assigned to a 10- to 15-min brief psychoeducation gambling intervention; a 10- to 15-min brief advice intervention addressing gambling norms, risk factors, and methods to prevent additional problems; or 4 50-min sessions of motivational enhancement therapy plus cognitive behavior therapy for reducing gambling (MET + CBT). Gambling and related problems were assessed at baseline and throughout 24 months. RESULTS: In the sample as a whole, days and dollars wagered and gambling problems decreased markedly from baseline through Month 5; thereafter, reductions in dollars wagered and gambling problems continued to decrease modestly but significantly, and days gambled remained constant. Brief advice significantly reduced days gambled between baseline and Month 5 relative to brief psychoeducation. The MET + CBT condition engendered no benefit beyond brief advice in terms of days gambled but did lead to more precipitous reductions in dollars gambled and problems experienced in the initial 5 months, and greater clinically significant improvements in gambling in both the short and long term. MET + CBT also resulted in initial decreases in self-reported alcohol use and problems but did not differentially impact self-reported illicit drug use or submission of positive samples. CONCLUSIONS: Gambling problems tend to dissipate over time regardless of the intervention applied, but offering MET + CBT was more efficacious in decreasing gambling than providing a brief single session intervention. (PsycINFO Database Record PMID- 27398782 TI - Posteromedial Versus Direct Posterior Approach for Posterior Cruciate Ligament Reinsertion. AB - Avulsion fractures of the posterior cruciate ligament (PCL) are usually found in pediatric populations. This study investigated which of 2 approaches posteromedial or direct posterior-enables easier PCL reinsertion. Ten fresh cadavers were studied using direct posterior (10 knees) and posteromedial (10 knees) approaches. In both, a guidewire was inserted into the tibial insertion of the PCL as perpendicular as possible to the coronal knee axis. Then, the angle between the guidewire and the horizontal plane of the table was measured. The mean angle of the guidewire was 8.6 degrees (SD=7.3 degrees ) with the direct posterior approach and 36.6 degrees (SD=14.3 degrees ) with the posteromedial approach (P=.005). The direct posterior approach allows a greater degree of freedom compared with the posteromedial approach to reach the PCL tibial insertion. [Orthopedics. 2016; 39(5):e1024-e1027.]. PMID- 27398783 TI - Patellar Resurfacing Versus Circumferential Denervation of the Patella in Total Knee Arthroplasty. AB - This study compared the rates of anterior knee pain and functional outcomes between resurfaced patellas and non-resurfaced patellas with a circumpatellar denervation. One hundred ten patients who underwent patellar resurfacing or a circumpatellar denervation were evaluated for knee pain and functional outcomes at a minimum of 2 years after total knee arthroplasty. There were no significant differences between the 2 groups regarding Knee Society Scores, anterior knee pain scores, or visual analog scale scores. The groups had similar incidences of anterior knee pain. Most patients reported no to mild effect of anterior knee pain on daily living. Patients in each group reported increased pain with kneeling, squatting, and departing an automobile. Similar proportions of patients were disappointed with their overall outcomes in each group. Circumpatellar denervation and patellar resurfacing during total knee arthroplasty lead to similar incidences of anterior knee pain. [Orthopedics. 2016; 39(5):e1019 e1023.]. PMID- 27398784 TI - Accuracy of Athletic Trainer and Physician Diagnoses in Sports Medicine. AB - It is standard practice in high school athletic programs for certified athletic trainers to evaluate and treat injured student athletes. In some cases, a trainer refers an athlete to a physician for definitive medical management. This study was conducted to determine the rate of agreement between athletic trainers and physicians regarding assessment of injuries in student athletes. All high school athletes who were injured between 2010 and 2012 at 5 regional high schools were included in a research database. All patients who were referred for physician evaluation and treatment were identified and included in this analysis. A total of 286 incidents met the inclusion criteria. A total of 263 (92%) of the athletic trainer assessments and physician diagnoses were in agreement. In the 23 cases of disagreement, fractures and sprains were the most common injuries. Kappa analysis showed the highest interrater agreement in injuries classified as dislocations and concussions and the lowest interrater agreement in meniscal/labral injuries and fractures. In the absence of a confirmed diagnosis, agreement among health care providers can be used to infer accuracy. According to this principle, as agreement between athletic trainers and physicians improves, there is a greater likelihood of arriving at the correct assessment and treatment plan. Athletic trainers are highly skilled professionals who are well trained in the evaluation of athletic injuries. The current study showed that additional training in identifying fractures may be beneficial to athletic trainers and the athletes they treat. [Orthopedics. 2016; 39(5):e944-e949.]. PMID- 27398785 TI - Biomechanical Study of a Subscapularis Repair Technique for Total Shoulder Arthroplasty. AB - Secure subscapularis repair is an essential element of total shoulder arthroplasty. Some surgeons prefer subscapularis peel because of ease of use, but some evidence suggests that lesser tuberosity osteotomy provides better fixation. The authors developed a novel, through-implant repair technique and performed a biomechanical study of its strength with cadaveric specimens. The authors obtained 20 matched pairs of cadaveric shoulders and inserted an uncemented short stemmed humeral prosthesis that facilitates through-implant repair in all specimens. For each cadaver, the subscapularis was repaired with lesser tuberosity osteotomy and standard suture technique on 1 side, and the contralateral subscapularis was repaired with a novel through-implant suture repair and subscapularis peel technique. Displacement of the subscapularis footprint, ultimate load to failure, and stiffness of each repair were measured and compared between fixation groups. Mean+/-SD displacement of the lesser tuberosity osteotomy group was 0.75+/-0.94 mm at 10 cycles and 2.24+/-2.76 mm at 500 cycles. Mean+/-SD load to failure was 612+/-185 N, and mean+/-SD ultimate stiffness was 119+/-32 N/mm. No significant differences were noted between the lesser tuberosity osteotomy group and the subscapularis peel group in mean+/-SD displacement at 10 cycles (1.09+/-1.30 mm, P=.31), mean+/-SD displacement at 500 cycles (2.85+/-2.43 mm, P=.26), mean+/-SD load to failure (683+/-274 N, P=.31), or mean+/-SD ultimate stiffness (117+/-37 N/mm, P=.88). In a biomechanical testing model, through-implant subscapularis repair provided secure fixation relative to currently accepted subscapularis repair techniques in total shoulder replacement. [Orthopedics. 2016; 39(5):e937-e943.]. PMID- 27398786 TI - The Prodrome of Extensor Pollicis Longus Tendonitis and Rupture: Rupture May Be Preventable. AB - Current literature suggests that tendonitis of the extensor pollicis longus (EPL) is a rare condition that has a high rate of progression to rupture. This study documents the prodrome of impending EPL rupture in patients with prior nondisplaced distal radial fracture. A retrospective study identified patients with EPL tendonitis or tendon rupture. Seven patients (6 females and 1 male) had sustained a nondisplaced distal radius fracture within the past year. Among these 7 patients, 4 eventually developed EPL tendon rupture and 3 had tendonitis without rupture. Of the 4 patients with EPL rupture, 2 presented to another provider before rupture with prodromal symptoms documented in the medical record, with pain and difficulty extending the affected thumb at the interphalangeal (IP) joint. The 3 patients with EPL tendonitis but no EPL tendon rupture all presented following a nondisplaced distal radius fracture with tenderness over the EPL tendon and pain with thumb motion. These 3 patients underwent EPL tendon decompression and subsequently did not go on to experience EPL rupture. Extensor pollicis longus tendonitis is a condition that is classically seen in the setting of nondisplaced distal radius fractures and often progresses to tendon rupture. In this study, the following prodrome of impending EPL rupture was identified: tenderness over the EPL tendon and Lister's tubercle and pain with thumb motion. This study suggests that patients with EPL tendonitis and possible impending rupture present with a prodrome of symptoms. If these patients can be identified, they may undergo EPL tendon decompression, which may prevent EPL tendon rupture. [Orthopedics. 2016; 39(5):318-322.]. PMID- 27398787 TI - Anconeus Epitrochlearis Muscle Causing Ulnar Neuropathy at the Elbow: Clinical and Neurophysiological Differential Diagnosis. AB - Ulnar neuropathy at the elbow is the second most frequent entrapment neuropathy and is considered idiopathic in most patients. However, several anatomic variations, including the anconeus epitrochlearis muscle, have been reported to cause ulnar nerve compression. The anconeus epitrochlearis muscle is a common anatomic variation, with a prevalence of up to 34%, but the clinical diagnosis of ulnar neuropathy of the elbow as a result of this variation is rare, with an unknown prevalence. It is a congenital accessory muscle between the medial humeral epicondyle and the olecranon that covers the posterior aspect of the cubital tunnel and is usually an operative finding, not a preoperative diagnosis. Ulnar neuropathy as a result of the anconeus epitrochlearis muscle usually has different characteristics than idiopathic disease, including younger age at onset, more rapid progression with a short duration of symptoms, distinct neurophysiology with velocity drop or conduction block of the ulnar nerve, and edema of the anconeus epitrochlearis muscle on magnetic resonance imaging. Neurophysiologic findings in anconeus epitrochlearis-associated ulnar neuropathy indicate subacute onset of symptoms rather than the chronic demyelinating process that is seen in idiopathic ulnar neuropathy. Medial elbow pain may be more exacerbated in these patients rather than the more common sensorial symptoms. This is probably the result of static compression of the nerve and increased cubital tunnel pressure, even when the elbow is in extension. This article describes a case of ulnar nerve entrapment of the elbow in a 28-year-old woman as a result of compression by the anconeus epitrochlearis muscle and includes magnetic resonance imaging findings, surgical correlations, and clinical and neurophysiologic findings. [Orthopedics. 2016; 39(5):e988-e991.]. PMID- 27398788 TI - Robotic Total Knee Arthroplasty: Surgical Assistant for a Customized Normal Kinematic Knee. AB - Although current total knee arthroplasty (TKA) is considered a highly successful surgical procedure, patients undergoing TKA can still experience substantial functional impairment and increased revision rates as compared with those undergoing total hip arthroplasty. Robotic-assisted surgery has been available clinically for almost 15 years and was developed, in part, to address these concerns. Robotic-assisted surgery aims to improve TKA by enhancing the surgeon's ability to optimize soft tissue balancing, reproduce alignment, and restore normal knee kinematics. Current systems include a robotic arm with a variety of different navigation systems with active, semi-active, or passive control. Semi active systems have become the dominant strategy, providing a haptic window through which the surgeon consistently prepares a TKA based on preoperative planning. A review of previous designs and clinical studies demonstrates that these robotic systems decrease variability and increase precision, primarily with the mechanical axis and restoration of the joint line. Future design objectives include precise planning and consistent intraoperative execution. Preoperative planning, intraoperative sensors, augmenting surgical instrumentation, and biomimetic surfaces will be used to re-create the 4-bar linkage system in the knee. Implants will be placed so that the knee functions with a medial pivot, lateral rollback, screw home mechanism, and patellar femoral tracking. Soft tissue balancing will become more than equalizing the flexion and extension gaps and will match the kinematics to a normal knee. Together, coupled with advanced knee designs, they may be the key to a patient stating, "My knee feels like my natural knee." [Orthopedics. 2016; 39(5):e822-e827.]. PMID- 27398789 TI - Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis. AB - Despite its status as one of the world's most prevalent and deadly bacterial pathogens, Mycobacterium tuberculosis (Mtb) infection is not routinely diagnosed by rapid and highly reliable tests. A program to discover Mtb-specific biomarkers recently identified two natural compounds, 1-tuberculosinyl adenosine (1-TbAd) and N(6)-tuberculosinyl adenosine (N(6)-TbAd). Based on their association with virulence, the lack of similar compounds in nature, the presence of multiple stereocenters, and the need for abundant products to develop diagnostic tests, synthesis of these compounds was considered to be of high value but challenging. Here, a multigram-scale stereoselective synthesis of 1-TbAd and N(6)-TbAd is described. As a key-step, a chiral auxiliary-mediated Diels-Alder cycloaddition was developed, introducing the three stereocenters with a high exo endo ratio (10:1) and excellent enantioselectivity (>98% ee). This constitutes the first entry into the stereoselective synthesis of diterpenes with the halimane skeleton. Computational studies explain the observed stereochemical outcome. PMID- 27398790 TI - Canola engineered with a microalgal polyketide synthase-like system produces oil enriched in docosahexaenoic acid. AB - Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, neither has been produced in commercially relevant amounts in a widely grown crop. We report expression of a microalgal polyketide synthase-like PUFA synthase system, comprising three multidomain polypeptides and an accessory enzyme, in canola (Brassica napus) seeds. This transgenic enzyme system is expressed in the cytoplasm, and synthesizes DHA and EPA de novo from malonyl-CoA without substantially altering plastidial fatty acid production. Furthermore, there is no significant impact of DHA and EPA production on seed yield in either the greenhouse or the field. Canola oil processed from field-grown grain contains 3.7% DHA and 0.7% EPA, and can provide more than 600 mg of omega-3 LC-PUFAs in a 14 g serving. PMID- 27398791 TI - Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames. AB - Increasing the levels of therapeutic proteins in vivo remains challenging. Antisense oligonucleotides (ASOs) are often used to downregulate gene expression or to modify RNA splicing, but antisense technology has not previously been used to directly increase the production of selected proteins. Here we used a class of modified ASOs that bind to mRNA sequences in upstream open reading frames (uORFs) to specifically increase the amounts of protein translated from a downstream primary ORF (pORF). Using ASO treatment, we increased the amount of proteins expressed from four genes by 30-150% in a dose-dependent manner in both human and mouse cells. Notably, systemic treatment of mice with ASO resulted in an ~80% protein increase of LRPPRC. The ASO-mediated increase in protein expression was sequence-specific, occurred at the level of translation and was dependent on helicase activity. We also found that the type of RNA modification and the position of modified nucleotides in ASOs affected translation of a pORF. ASOs are a useful class of therapeutic agents with broad utility. PMID- 27398793 TI - Visible-Frequency Dielectric Metasurfaces for Multiwavelength Achromatic and Highly Dispersive Holograms. AB - Dielectric metasurfaces built up with nanostructures of high refractive index represent a powerful platform for highly efficient flat optical devices due to their easy-tuning electromagnetic scattering properties and relatively high transmission efficiencies. Here we show visible-frequency silicon metasurfaces formed by three kinds of nanoblocks multiplexed in a subwavelength unit to constitute a metamolecule, which are capable of wavefront manipulation for red, green, and blue light simultaneously. Full phase control is achieved for each wavelength by independently changing the in-plane orientations of the corresponding nanoblocks to induce the required geometric phases. Achromatic and highly dispersive meta-holograms are fabricated to demonstrate the wavefront manipulation with high resolution. This technique could be viable for various practical holographic applications and flat achromatic devices. PMID- 27398795 TI - Return to Work Rates After Single-level Cervical Fusion for Degenerative Disc Disease Compared With Fusion for Radiculopathy in a Workers' Compensation Setting. AB - STUDY DESIGN: A retrospective comparative cohort study. OBJECTIVE: To compare return to work (RTW) rates for patients who underwent single-level cervical fusion for radiculopathy compared with fusion for degenerative disc disease (DDD) as an indication for surgery. SUMMARY OF BACKGROUND DATA: Studies have shown that workers' compensation subjects have less favorable surgical and functional outcomes compared with the general population. Cervical decompression and fusion have provided great results with relieving radicular symptoms. Fusion for DDD, however, remains controversial. METHODS: We retrospectively collected data of 21 169 subjects with cervical comorbidities who filed their claims for work-related injuries with Ohio Bureau of Workers' Compensation (BWC) between 1993 and 2011. The primary outcome was whether subjects met RTW criteria within 3-year follow-up after fusion. The secondary outcome measures and data on presurgical characteristics and secondary outcomes of each cohort were also collected. RESULTS: Successful RTW status was affected by a number of presurgical risk factors: DDD as an indication for surgery, age of more than 50 years, out of work for more than 6 months, psychological evaluation, opioid use, legal litigation, and permanent disability. The DDD group had lower rate of successful RTW status (50.9%) and was less likely to have a sustained RTW status (odds ratio = 0.61, 95% confidence interval: 0.48-0.79, P = 0.0001) compared with the radiculopathy group (successful RTW rate 62.9%). RTW rate within 1 year after surgery was lower in the DDD group (39.9%) compared with the radiculopathy group (53.1%; P = 0.0001). DDD patients were absent 112 days more on average after surgery compared with radiculopathy patients (P = 0.0003). CONCLUSION: Cervical fusion for DDD is associated with lower rate of successful RTW status when compared with fusion for radiculopathy in a worker's compensation setting. The decision to include surgical intervention in the management plan of cervical DDD should be approached with caution as the surgical outcome might not necessarily lead to improved postsurgical functionality and achieve sustained early RTW. LEVEL OF EVIDENCE: 4. PMID- 27398792 TI - A recellularized human colon model identifies cancer driver genes. AB - Refined cancer models are needed to bridge the gaps between cell line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. We identified 38 candidate invasion-driver genes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been previously implicated in colorectal cancer progression. Six invasion-driver genes that have not, to our knowledge, been previously described were validated in vitro using cell proliferation, migration and invasion assays and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology. PMID- 27398794 TI - Do Cancer-Related Beliefs Influence the Severity, Incidence, and Persistence of Psychological Symptoms? AB - BACKGROUND: Previous studies have suggested that negative beliefs about cancer may impair patients' psychological well-being, but only a few of these studies focused on specific psychological symptoms, and many were cross-sectional. OBJECTIVE: The aim of this study was to investigate longitudinally the relationship of cancer-related cognitions with the severity, incidence, and persistence of anxiety, fear of cancer recurrence, depression, and insomnia symptoms during an 18-month period. METHODS: Patients scheduled to undergo surgery for cancer (N = 962) completed a questionnaire assessing cancer-related cognitions at baseline (T1), the Hospital Anxiety and Depression Scale, the severity subscale of the Fear of Cancer Recurrence Inventory, and the Insomnia Severity Index at baseline (T1) and 2 (T2), 6 (T3), 10 (T4), 14 (T5), and 18 (T6) months later. RESULTS: Group * time factorial analyses using mixed models revealed that participants endorsing more negative cancer-related cognitions consistently reported more severe symptoms throughout the 18-month period. Logistic regression analyses suggested that endorsing more negative cancer related cognitions at T1 significantly increased incidence and persistence rates of clinical levels of psychological symptoms. CONCLUSIONS: These findings suggest that the endorsement of negative cancer-related beliefs at the perioperative period influences the longitudinal evolution of anxiety, fear of cancer recurrence, depression, and insomnia symptoms in the following months. IMPLICATIONS FOR PRACTICE: These results highlight the relevance of using cognitive restructuring early during the cancer care trajectory to potentially revise erroneous beliefs about cancer and prevent the incidence and persistence of psychological disturbances over time. PMID- 27398796 TI - Effect of Antifibrinolytic Therapy on Complications, Thromboembolic Events, Blood Product Utilization, and Fusion in Adult Spinal Deformity Surgery. AB - STUDY DESIGN: A multicenter, prospective, consecutive database of surgical patients with adult spinal deformity (ASD). OBJECTIVE: This study investigated the use of antifibrinolytic (AF) therapy in ASD surgery. SUMMARY OF BACKGROUND DATA: AF therapy has been shown to be effective in preventing blood loss in some settings. Its effect on major and minor perioperative complications, blood product utilization, vascular events, and postoperative fusion in patients undergoing ASD surgery remains unclear. METHODS: All patients with data on AF use were included. Parameters of blood utilization included transfusion rates and units of packed red blood cells and fresh frozen plasma transfused. Thromboembolic events included stroke, deep vein thrombosis, and pulmonary embolus. Multivariate regression was used, accounting for confounders. RESULTS: Four hundred three patients were included. One hundred thirty-seven patients received aminocaproic acid (EACA), 81 received tranexamic acid (TXA), and 185 received no AFs. The use of AF was associated with a decrease in transfusion (EACA: odds ratio [OR] = 0.38, P = 0.043; TXA: OR = 0.31, P = 0.047), a decrease in the number of units of packed red blood cells transfused (EACA: incidence risk ratio [IRR] = 0.45, P = 0.0005; TXA: IRR = 0.7, P = 0.0005), and a decrease in the number of fresh frozen plasma transfused (EACA: IRR = 0.65, P = 0.003; TXA: IRR = 0.67, P = 0.006). AF use was associated with an increase in minor intraoperative complications (EACA: IRR = 2.15, P = 0.008; TXA: IRR = 2.12, P = 0.011). TXA use (but not EACA) was associated with a decrease in the incidence of major perioperative complications compared with no AF (IRR = 0.37, P = 0.019). There was no difference in the incidence of thromboembolic events. CONCLUSION: TXA or EACA use was associated with increased minor intraoperative complications. TXA was associated with decreased major perioperative complications. AF was associated with decreased utilization of blood products without an increased rate of thromboembolic events. Given the nature of this study, transfusion threshold was not standardized. Future studies with rigid criteria for transfusion should be prospectively performed to better evaluate the impact of AF during ASD surgery. LEVEL OF EVIDENCE: 3. PMID- 27398797 TI - Effectiveness of Selective Thoracic Fusion in the Surgical Treatment of Syringomyelia-associated Scoliosis: A Case-control Study With Long-term Follow up. AB - STUDY DESIGN: A retrospective case-control studyOBJECTIVE.: The aim of the study was to investigate the effectiveness of selective thoracic fusion in the surgical treatment of patients with syringomyelia-associated scoliosis. SUMMARY OF BACKGROUND DATA: Selective thoracic fusion technique was introduced to treat idiopathic scoliosis patients with major thoracic curve. Theoretically, such therapeutic philosophy could be applied to syringomyelia patients. There is no previous study that specifically addresses the effectiveness of selective thoracic fusion in patients with syringomyelia-associated scoliosis. METHODS: Two groups of scoliosis patients were enrolled, including 52 patients with syringomyelia-associated scoliosis and 52 patients with adolescent idiopathic scoliosis. Selective thoracic fusion was performed for both groups. Radiographic parameters including Cobb angle, apical vertebral translation, trunk shift, thoracic kyphosis (TK), lumbar lordosis, and sagittal vertical axis were measured on the standing posteroanterior and lateral radiographs before surgery, 1 week postoperatively and at the final follow-up, respectively. Inter- and intragroup comparisons were performed for each variable. RESULTS: Patients of the two groups were matched in terms of age, sex, fusion levels, duration of follow-up, and all preoperative radiographic parameters except for TK. At the final follow-up, the coronal correction of the thoracic curve was comparable between the two groups (58.8 +/- 10.2% vs. 61.3 +/- 8.7%, P = 0.25). Moreover, the two groups were observed to have a similar improvement of lumbar curve (62.4 +/- 7.3% vs. 64.9 +/ 6.9%, P = 0.33). The mean correction loss of thoracic curve and lumbar curve in syringomyelia group were 3.6 +/- 3.2% and 5.3 +/- 1.8% respectively, showing no statistical difference when compared with those of adolescent idiopathic scoliosis group. The sagittal spinal alignments of the two groups, including TK and lumbar lordosis, were similarly maintained during the follow-up. CONCLUSION: Syringomyelia-associated scoliosis can be successfully corrected through selective thoracic fusion surgery with a promising long-term surgical outcome. LEVEL OF EVIDENCE: 3. PMID- 27398798 TI - Real-Time Biological Annotation of Synthetic Compounds. AB - Organic chemists are able to synthesize molecules in greater number and chemical complexity than ever before. Yet, a majority of these compounds go untested in biological systems, and those that do are often tested long after the chemist can incorporate the results into synthetic planning. We propose the use of high dimensional "multiplex" assays, which are capable of measuring thousands of cellular features in one experiment, to annotate rapidly and inexpensively the biological activities of newly synthesized compounds. This readily accessible and inexpensive "real-time" profiling method can be used in a prospective manner to facilitate, for example, the efficient construction of performance-diverse small molecule libraries that are enriched in bioactives. Here, we demonstrate this concept by synthesizing ten triads of constitutionally isomeric compounds via complexity-generating photochemical and thermal rearrangements and measuring compound-induced changes in cellular morphology via an imaging-based "cell painting" assay. Our results indicate that real-time biological annotation can inform optimization efforts and library syntheses by illuminating trends relating to biological activity that would be difficult to predict if only chemical structure were considered. We anticipate that probe and drug discovery will benefit from the use of optimization efforts and libraries that implement this approach. PMID- 27398799 TI - Insights into the Mechanisms of the Acute Kidney Injury-to-Chronic Kidney Disease Continuum. AB - Acute kidney injury (AKI) is an increasingly common clinical problem with significant impact on long-term patient outcome. Recent clinical trials demonstrate that AKI is closely related to the progression of chronic kidney disease (CKD) and end-stage renal disease, though the precise mechanisms linking AKI to CKD remain unclear. While inflammation, microvascular rarefaction and hypoxia are involved in the AKI-to-CKD continuum, proximal tubule injury seems to play an important role in the progression of CKD. In this review, we focus on the mechanisms of the AKI-to-CKD continuum, especially the mechanism by which injury to the proximal tubules triggers progression to CKD. Elucidating the mechanisms involved in the AKI-to-CKD continuum will support the development of therapeutic options to prevent progression from AKI to CKD. (c) 2016 S. Karger AG, Basel. PMID- 27398800 TI - Mechanisms of the Evolutionary Chromosome Plasticity: Integrating the 'Centromere from-Telomere' Hypothesis with Telomere Length Regulation. AB - The 'centromere-from-telomere' hypothesis proposed by Villasante et al. [2007a] aims to explain the evolutionary origin of the eukaryotic chromosome. The hypothesis is based on the notion that the process of eukaryogenesis was initiated by adaptive responses of the symbiont eubacterium and its archaeal host to their new conditions. The adaptive responses included fragmentation of the circular genome of the host into multiple linear fragments with free DNA ends. The action of mobile genetic elements stabilized the free DNA ends resulting in the formation of proto-telomeres. Sequences next to the proto-telomeres, the subtelomeric sequences, were immediately targeted as the new cargo by the tubulin based cytoskeleton, thus becoming proto-centromeres. A period of genomic instability followed. Eventually, functioning centromeres and telomeres emerged heralding the arrival of the eukaryotic chromosome in the evolution. This paper expands the 'centromere-from-telomere' hypothesis by integrating it with 2 sets of data: chromosome-specific telomere length distribution and chromomere size gradient. The integration adds a new dimension to the hypothesis but also provides an insight into the mechanisms of chromosome plasticity underlying karyotype evolution. PMID- 27398801 TI - Tuning the Schottky contacts in the phosphorene and graphene heterostructure by applying strain. AB - The structures and electronic properties of the phosphorene and graphene heterostructure are investigated by density functional calculations using the hybrid Heyd-Scuseria-Ernzerhof (HSE) functional. The results show that the intrinsic properties of phosphorene and graphene are preserved due to the weak van der Waals contact. But the electronic properties of the Schottky contacts in the phosphorene and graphene heterostructure can be tuned from p-type to n-type by the in-plane compressive strains from -2% to -4%. After analyzing the total band structure and density of states of P atom orbitals, we find that the Schottky barrier height (SBH) is determined by the P-pz orbitals. What is more, the variation of the work function of the phosphorene monolayer and the graphene electrode and the Fermi level shift are the nature of the transition of Schottky barrier from n-type Schottky contact to p-type Schottky contact in the phosphorene and graphene heterostructure under different in-plane strains. We speculate that these are general results of tuning of the electronic properties of the Schottky contacts in the phosphorene and graphene heterostructure by controlling the in-plane compressive strains to obtain a promising method to design and fabricate a phosphorene-graphene based field effect transistor. PMID- 27398802 TI - AgNO3 as nitrogen source for rhodium(iii)-catalyzed synthesis of 2-aryl-2H benzotriazoles from azobenzenes. AB - A new approach has been established for Rh(iii)-catalyzed direct aza oxidative cyclization of non-prefunctionalized azobenzenes to provide 2-aryl-2H benzotriazoles in good yields, in which AgNO3 instead of conventional azide reagents for the first time functions as the nitrogen source for the nitrogenation reaction. Preliminary mechanistic studies suggest that the Rh(iii) catalyst could account for the nitration reaction, and subsequently cationic silver species might both play a vital role in the fission of the nitrogen-oxygen bonds in nitro groups and promote aza oxidative cyclization. PMID- 27398803 TI - Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control. AB - BACKGROUND: The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. PATIENTS AND METHODS: 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. RESULTS: Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33 3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). CONCLUSIONS: Risk adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers. PMID- 27398805 TI - An Independent Psychometric Evaluation of the PROMS Measure of Music Perception Skills. AB - The Profile of Music Perception Skills (PROMS) is a recently developed measure of perceptual music skills which has been shown to have promising psychometric properties. In this paper we extend the evaluation of its brief version to three kinds of validity using an individual difference approach. The brief PROMS displays good discriminant validity with working memory, given that it does not correlate with backward digit span (r = .04). Moreover, it shows promising criterion validity (association with musical training (r = .45), musicianship status (r = .48), and self-rated musical talent (r = .51)). Finally, its convergent validity, i.e. relation to an unrelated measure of music perception skills, was assessed by correlating the brief PROMS to harmonic closure judgment accuracy. Two independent samples point to good convergent validity of the brief PROMS (r = .36; r = .40). The same association is still significant in one of the samples when including self-reported music skill in a partial correlation (rpartial = .30; rpartial = .17). Overall, the results show that the brief version of the PROMS displays a very good pattern of construct validity. Especially its tuning subtest stands out as a valuable part for music skill evaluations in Western samples. We conclude by briefly discussing the choice faced by music cognition researchers between different musical aptitude measures of which the brief PROMS is a well evaluated example. PMID- 27398804 TI - Regional Influence of Aerosol Emissions from Wildfires Driven by Combustion Efficiency: Insights from the BBOP Campaign. AB - Wildfires are important contributors to atmospheric aerosols and a large source of emissions that impact regional air quality and global climate. In this study, the regional and nearfield influences of wildfire emissions on ambient aerosol concentration and chemical properties in the Pacific Northwest region of the United States were studied using real-time measurements from a fixed ground site located in Central Oregon at the Mt. Bachelor Observatory (~2700 m a.s.l.) as well as near their sources using an aircraft. The regional characteristics of biomass burning aerosols were found to depend strongly on the modified combustion efficiency (MCE), an index of the combustion processes of a fire. Organic aerosol emissions had negative correlations with MCE, whereas the oxidation state of organic aerosol increased with MCE and plume aging. The relationships between the aerosol properties and MCE were consistent between fresh emissions (~1 h old) and emissions sampled after atmospheric transport (6-45 h), suggesting that biomass burning organic aerosol concentration and chemical properties were strongly influenced by combustion processes at the source and conserved to a significant extent during regional transport. These results suggest that MCE can be a useful metric for describing aerosol properties of wildfire emissions and their impacts on regional air quality and global climate. PMID- 27398808 TI - Equation of Motion Theory for Excited States in Variational Monte Carlo and the Jastrow Antisymmetric Geminal Power in Hilbert Space. AB - An equation of motion formalism for excited states in variational Monte Carlo is derived, and a pilot implementation for the Jastrow-modified antisymmetric geminal power is tested. In single excitations across a range of small molecules, this combination is shown to be intermediate in accuracy between configuration interaction singles and equation of motion coupled cluster with singles and doubles. For double excitations, energy errors are found to be similar to those for coupled cluster. PMID- 27398807 TI - Functional Crosstalk between the PP2A and SUMO Pathways Revealed by Analysis of STUbL Suppressor, razor 1-1. AB - Posttranslational modifications (PTMs) provide dynamic regulation of the cellular proteome, which is critical for both normal cell growth and for orchestrating rapid responses to environmental stresses, e.g. genotoxins. Key PTMs include ubiquitin, the Small Ubiquitin-like MOdifier SUMO, and phosphorylation. Recently, SUMO-targeted ubiquitin ligases (STUbLs) were found to integrate signaling through the SUMO and ubiquitin pathways. In general, STUbLs are recruited to target proteins decorated with poly-SUMO chains to ubiquitinate them and drive either their extraction from protein complexes, and/or their degradation at the proteasome. In fission yeast, reducing or preventing the formation of SUMO chains can circumvent the essential and DNA damage response functions of STUbL. This result indicates that whilst some STUbL "targets" have been identified, the crucial function of STUbL is to antagonize SUMO chain formation. Herein, by screening for additional STUbL suppressors, we reveal crosstalk between the serine/threonine phosphatase PP2A-Pab1B55 and the SUMO pathway. A hypomorphic Pab1B55 mutant not only suppresses STUbL dysfunction, but also mitigates the phenotypes associated with deletion of the SUMO protease Ulp2, or mutation of the STUbL cofactor Rad60. Together, our results reveal a novel role for PP2A-Pab1B55 in modulating SUMO pathway output, acting in parallel to known critical regulators of SUMOylation homeostasis. Given the broad evolutionary functional conservation of the PP2A and SUMO pathways, our results could be relevant to the ongoing attempts to therapeutically target these factors. PMID- 27398809 TI - Central venous catheter (CVC) removal for patients of all ages with candidaemia. AB - BACKGROUND: Candida bloodstream infections most often affect those already suffering serious, potentially life-threatening conditions and often cause significant morbidity and mortality. Most affected persons have a central venous catheter (CVC) in place. The best CVC management in these cases has been widely debated in recent years, while the incidence of candidaemia has markedly increased. OBJECTIVES: The main purpose of this review is to examine the impact of removing versus retaining a CVC on mortality in adults and children with candidaemia who have a CVC in place. SEARCH METHODS: We searched the following databases from inception to 3 December 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP), the Commonwealth Agricultural Bureau (CAB), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We searched for missed, unreported and ongoing trials in trial registries and in reference lists of excluded articles. SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) and quasi-RCTs involving adults and children with candidaemia and in which participants were randomized for removal of a CVC (the intervention under study), irrespective of publication status, date of publication, blinding status, outcomes published or language.However, two major factors make the conduct of RCTs in this population a difficult task: the large sample size required to document the impact of catheter removal in terms of overall mortality; and lack of economic interest from the industry in conducting such a trial. DATA COLLECTION AND ANALYSIS: Our primary outcome measure was mortality. Several secondary outcome measures such as required time for clearance of blood cultures for Candida species, frequency of persistent candidaemia, complications, duration of mechanical ventilation and length of stay in the intensive care unit (ICU) and in the hospital were planned, as were various subgroup and sensitivity analyses, according to our protocol. We assessed papers and abstracts for eligibility and resolved disagreements by discussion. However, we were not able to include any RCTs or quasi-RCTS in this review and, as a result, have carried out no meta-analyses. However, we have chosen to provide a brief overview of excluded observational studies. MAIN RESULTS: We found no RCT and thus no available data for evaluation of the primary outcome (mortality) nor secondary outcomes or adverse effects. Therefore, we conducted no statistical analysis.A total of 73 observational studies reported on various clinically relevant outcomes following catheter removal or catheter retention. Most of these excluded, observational studies reported a beneficial effect of catheter removal in patients with candidaemia. None of the observational studies reported results in favour of retaining a catheter. However, the observational studies were very heterogeneous with regards to population, pathogens and interventions. Furthermore, they suffered from confounding by indication and an overall high risk of bias. As a consequence, we are not able to provide recommendations or to draw firm conclusions because of the difficulties involved in interpreting the results of these observational studies (very low quality of evidence, GRADE - Grades of Recommendation, Assessment, Development and Evaluation Working Group). AUTHORS' CONCLUSIONS: Despite indications from observational studies in favour of early catheter removal, we found no eligible RCTs or quasi-RCTs to support these practices and therefore could draw no firm conclusions. At this stage, RCTs have provided no evidence to support the benefit of early or late catheter removal for survival or other important outcomes among patients with candidaemia; no evidence with regards to assessment of harm or benefit with prompt central venous catheter removal and subsequent re-insertion of new catheters to continue treatment; and no evidence on optimal timing of insertion of a new central venous catheter. PMID- 27398810 TI - Excited-State Decay in the Photoisomerisation of Azobenzene: A New Balance between Mechanisms. AB - The mechanism of the photoisomerisation of azobenzene has been studied by means of multiconfigurational ab initio calculations. Our results show that it is necessary to account for the dynamic electron correlation in the location of the critical points (CASPT2 optimizations) to obtain a correct description of the topography of the potential energy surfaces of the low energy singlet excited states. By using this methodology, we have found that the state populated by the initial excitation is the S2 (pipi*) state, which decays very efficiently to the S1 (npi*) state at a pedal-like non-rotated geometry. In the S1 state, relaxation leads to a rotated geometry where the system decays to the ground state, in which further relaxation can lead to either the trans or cis geometries. However, the S1 /S0 conical intersection seam also extends to planar geometries, so this reaction path is also accessible for rotation-constrained systems. Our results explain the experimental observations satisfactorily. PMID- 27398811 TI - Perioperative Management and Outcome of Bilateral Adrenalectomy in 9 Dogs. AB - OBJECTIVE: To report perioperative care, postoperative management, and long-term outcomes in dogs undergoing bilateral adrenalectomy. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs undergoing bilateral adrenalectomy from 2008 to 2013 (n=9). METHODS: Data retrieved from the record, when available, included signalment, preoperative clinical signs, laboratory data, diagnostic imaging, blood pressure measurement, preoperative treatment for adrenal gland disease, intraoperative procedures, treatments and complications, postoperative treatment and diagnostics during hospitalization, diagnostics and management following discharge, histopathologic diagnosis, and survival. RESULTS: Seven dogs underwent concurrent bilateral adrenalectomy and 2 dogs had staged adrenalectomy. Surgery was uncomplicated in most cases. All dogs received IV dexamethasone SP intraoperatively. Eight dogs received intramuscular desoxycorticosterone pivalate intraoperatively. Histopathology revealed adrenocortical adenoma (7 dogs), adrenocortical carcinoma (4), pheochromocytoma (6), and adrenocortical atrophy (1). One dog died perioperatively and the remainder died due to unrelated causes. Postoperative management of hypoadrenocorticism included oral prednisone and intramuscular desoxycorticosterone pivalate (6 dogs), oral prednisone and fludrocortisone (1), and oral fludrocortisone alone (1). The median survival time in dogs surviving to hospital discharge was 525 days (range 67-966 days). No dogs developed metastatic disease or died due to signs of hypoadrenocorticism. CONCLUSION: Based on the cases reported here, the perioperative mortality in dogs undergoing bilateral adrenalectomy may be lower than previously reported. Management of postoperative hypoadrenocorticism is both achievable and straightforward. PMID- 27398812 TI - Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study. AB - AIMS: This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast. METHODS AND RESULTS: Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power. CONCLUSIONS: The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. PMID- 27398813 TI - End-ischemic reconditioning of liver allografts: Controlling the rewarming. AB - Different nonhypothermic preservation modalities have shown beneficial effects in liver transplantation models. This study compares controlled oxygenated rewarming (COR) to normothermic machine perfusion (NMP) to resuscitate liver grafts following cold storage (CS). Porcine livers were preserved for 18 hours by CS. Before reperfusion, the grafts were put on a machine perfusion device (Liver Assist) for 3 hours and were randomly assigned to COR (n = 6) or NMP (n = 5) and compared to standard CS. COR was carried out with the new Custodiol-N solution, slowly increasing temperature from 8 degrees C to 20 degrees C during the first 90 minutes. NMP was carried out with diluted autologous blood at 37 degrees C for 3 hours. In both cases, the perfusate was oxygenated to partial pressure of oxygen > 500 mm Hg. Then liver viability was tested for 180 minutes during in vitro isolated sanguineous reperfusion. Activity of the mitochondrial caspase 9 was lower after COR. Measurement of tissue adenosine triphosphate and total adenine nucleotides at the end of the reconditioning period showed better energetic recovery after COR. COR also resulted in significantly lower enzyme leakage and higher bile production (P < 0.05) during reperfusion. This first comparison of COR and NMP as end-ischemic reconditioning modalities demonstrates superior results in terms of mitochondrial integrity resulting in better energetic recovery, less hepatocellular injury, and ultimately superior function in favor of COR. Liver Transplantation 22 1223-1230 2016 AASLD. PMID- 27398814 TI - Citation inflation: when the adoption of a new technique becomes an avenue for publication. PMID- 27398815 TI - Emergency department visits by pediatric patients for poisoning by prescription opioids. AB - BACKGROUND: Prescription medication abuse is an increasingly recognized problem in the United States. As more opioids are being prescribed and abused by adults, there is an increased risk of both accidental and intentional exposure to children and adolescents. The impact of pediatric exposures to prescription pain pills has not been well studied. OBJECTIVES: We sought to evaluate emergency department (ED) visits for poisoning by prescription opioids in pediatric patients. METHODS: This retrospective study looked at clinical and demographic data from the Nationwide Emergency Department Sample (NEDS) from 2006 to 2012. RESULTS: There were 21,928 pediatric ED visits for prescription opioid poisonings and more than half were unintentional. There was a bimodal age distribution of patients, with slightly more than half occurring in females. The majority of patients were discharged from the ED. More visits in the younger age group (0-5 years) were unintentional, while the majority of visits in the adolescent age group (15-17 years) were intentional. Mean charge per discharge was $1,840 and $14,235 for admissions and surmounted to over $81 million in total charges. CONCLUSION: Poisonings by prescription opioids largely impact both young children and adolescents. These findings can be used to help target this population for future preventive efforts. PMID- 27398816 TI - Rural people who inject drugs: A cross-sectional survey addressing the dimensions of access to secondary needle and syringe program outlets. AB - OBJECTIVE: To better understand issues related to access to injecting equipment for people who inject drugs (PWID) in a rural area of New South Wales (NSW), Australia. DESIGN: Cross-sectional face-to-face survey using convenience and snowball sampling. SETTING: Six regional and rural population centres in Northern NSW, within the Hunter New England Local Health District. PARTICIPANTS: The sample included 190 PWID who had accessed a needle and syringe program outlet within 4 weeks of the survey. MAIN OUTCOME MEASURES: Data include demographic information, preferred location for accessing injecting equipment, reasons for that preference, whether they obtained enough equipment, travelling distance to an NSP and self-reported hepatitis C virus status. RESULTS: Sixty percent self identified as Aboriginal people. The median age of respondents was 32 years and 60% were men. A significantly larger proportion (P < 0.05) of the Aboriginal respondents were women (27% versus 11.6%) and younger (37.6 versus 12.7%) compared to non-Aboriginal respondents. Most preferred to access injecting equipment at a community health facility (62.6%), as opposed to other secondary outlets, where they gained enough equipment (67.4%). Just over 80% said they were tested for HCV in the past year, with about 37% told they had tested positive. CONCLUSIONS: There are complex dimensions affecting how rural PWID access secondary NSP outlets. Although access is similarly limited as other rural health services because of the nature of injecting drug use and sensitivities existing in rural communities, there is potential for application of unique access models, such as, promoting secondary distribution networks. PMID- 27398817 TI - Evaluating a humane alternative to the bark collar: Automated differential reinforcement of not barking in a home-alone setting. AB - The aim of this study was to develop a humane alternative to the traditional remote devices that deliver punishers contingent on home-alone dog barking. Specifically, we evaluated the use of remote delivery of food contingent on intervals of not barking during the pet owner's absence. In Experiment 1, 5 dogs with a history of home-alone nuisance barking were recruited. Using an ABAB reversal design, we demonstrated that contingent remote delivery of food decreased home-alone barking for 3 of the dogs. In Experiment 2, we demonstrated that it is possible to thin the differential-reinforcement-of-other-behavior (DRO) schedule gradually, resulting in a potentially more acceptable treatment. Our results benefit the dog training community by providing a humane tool to combat nuisance barking. PMID- 27398819 TI - Gut microbiome analysis in neuromyelitis optica reveals overabundance of Clostridium perfringens. AB - T cells from neuromyelitis optica (NMO) patients, which recognize the immunodominant epitope of aquaporin-4, exhibit Th17 polarization and cross-react with a homologous sequence of a Clostridium perfringens adenosine triphosphate binding cassette transporter. Therefore, this commensal microbe might participate in NMO pathogenesis. We examined the gut microbiome by PhyloChip G3 from 16 NMO patients, 16 healthy controls (HC), and 16 multiple sclerosis patients. A significant difference in the abundance of several microbial communities was observed between NMO and HC (Adonis test, p = 0.001). Strikingly, C. perfringens was overrepresented in NMO (p = 5.24 * 10(-8) ). These observations support a potential role for C. perfringens in NMO pathogenesis. Ann Neurol 2016;80:443 447. PMID- 27398818 TI - In Vitro Effects of the Neolignan 2,3-Dihydrobenzofuran Against Leishmania Amazonensis. AB - Leishmaniasis is an infectious disease complex caused by protozoa from the Leishmania genus, which presents a broad spectrum of clinical manifestations: cutaneous, mucocutaneous and visceral forms. The current treatments are unsatisfactory considering that few drugs are available and present some level of toxicity. Many lignans and neolignans have been used for the development of new antileishmania drugs. The capability in vitro of the neolignan 2,3 dihydrobenzofuran (2,3-DBF), a commonly found constituent of propolis and other plants, to inhibit the growth of promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis was investigated. The cytotoxicity of this compound was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) test in BALB/c murine macrophages and human erythrocyte lysis assay. The 2,3-DBF was active against promastigote (IC50 =1.042 MUM) and amastigote (IC50 =1.43 MUM) forms, indicating a potent antileishmanial effect. There was no evidence of cytotoxicity to macrophages or erythrocytes at concentrations ranging from 13 to 0.5 MUM, after 48 hr of exposure. The antileishmanial activity is probably mediated by the activation of macrophages, because treatment with 2,3-DBF increases both phagocytic and lysosomal activities, as well as the nitrite (NO2- ) levels. These results suggest that 2,3 DBF may be a potential candidate for the development of a new promising antileishmanial drug. Further studies are needed to determine its potential in vivo effect as well as additional mechanisms underlying the antileishmanial and immunomodulatory activities. PMID- 27398820 TI - The NIH Countermeasures Against Chemical Threats Program: overview and special challenges. AB - Intentional exposures to toxic chemicals can stem from terrorist attacks, such as the release of sarin in the Tokyo subway system in 1995, as well as from toxic industrial accidents that are much more common. Developing effective medical interventions is a critical component of the overall strategy to overcome the challenges of chemical emergencies. These challenges include the rapid and lethal mode of action of many toxic chemicals that require equally fast-acting therapies, the large number of chemicals that are considered threats, and the diverse demographics and vulnerabilities of those who may be affected. In addition, there may be long-term deleterious effects in survivors of a chemical exposure. Several U.S. federal agencies are invested in efforts to improve preparedness and response capabilities during and after chemical emergencies. For example, the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) Program supports investigators who are developing therapeutics to reduce mortality and morbidity from chemical exposures. The program awards grants to individual laboratories and includes contract resource facilities and interagency agreements with Department of Defense laboratories. The range of high-quality research within the NIH CounterACT Program network is discussed. PMID- 27398822 TI - Role of tagged SNPs of the AGT gene in causing susceptibility to essential hypertension. AB - AIM: Angiotensinogen (AGT) is one of the candidate genes that has been extensively investigated for association of its variants with essential hypertension. Studies focusing on the contribution of tagged single nucleotide polymorphisms (SNPs) in the AGT gene are limited and lacking from Indian population. Hence, the present study was carried out to examine the role of five tagged SNPs viz., g.6147G>A (rs7539020), g.5978A>G (rs2493134); g.6241T>C (rs1078499), g.7781G>T (rs11122577), and g.5855G>A (rs3789678) in the development of hypertension. MATERIALS AND METHODS: 202 hypertensives and 222 normotensives were screened for five tagged SNPs using the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). RESULTS: The present study revealed significant association of g.5855G>A polymorphism with essential hypertension in different logistic regression models wherein protection was conferred by g.5855G>A against developing the condition. The polymorphism led to the creation of new exonic splicing enhancer and destruction of exonic splicing silencer site thereby enhancing the process of mRNA splicing. The haplotypes AGTG and GACG were found to have a significant protective effect. Other polymorphisms did not show any significant association with hypertension. CONCLUSION: The present study is the first one to report the protective role of g.5855G>A polymorphism in the development of essential hypertension. The results reflect possibility of ethnic variation in the contribution of g.5855G>A polymorphism of the AGT gene to essential hypertension. PMID- 27398823 TI - Surgical Treatment of Paraesophageal Hernias: A Review. AB - The management of paraesophageal hernia (PEH) can be challenging due to the lack of consensus regarding indications and principles of operative treatment. In addition, data about the pathophysiology of the hernias are scant. Therefore, the goal of this review is to shed light and describe the classification, pathophysiology, clinical presentation, and indications for treatment of PEHs, and provide an overview of the surgical management and a description of the technical principles of the repair. PMID- 27398824 TI - Effect of Electronic Messaging on Glucose Control and Hospital Admissions Among Patients with Diabetes. AB - BACKGROUND: Electronic messaging (EM) is increasingly utilized among patients with diabetes, but it is unclear whether it is associated with improved glycemic control, hospital admissions, or emergency visits. METHODS: Patients who were seen over a 1 year period at an academic endocrinology clinic with a diagnosis of diabetes were categorized according to portal activation and whether EMs were actually sent. The association between EM and HbA1c and inpatient or emergency department (ED) visits was further characterized using multivariable (MV) linear or logistic regression models. RESULTS: A total of 867 patients were using EM (active user group), 1207 patients had activated the patient portal but did not use the EM function (active nonuser group), and 1542 patients had not activated the patient portal (inactive group). There were important disparities in race, age, income, and other variables across groups. The HbA1c was 7.7% +/- 1.5%, 8.4% +/- 1.9%, and 8.2% +/- 1.8% among the active user, active nonuser, and inactive groups, respectively (P < 0.0001). After controlling for other factors, EM was associated with a 0.25% (SE 0.04%) lower HbA1c compared with the active nonuser group and a 0.19% (SE 0.04%) lower HbA1c compared with the inactive group (P < 0.0001 for both). However, EM frequency was not associated with HbA1c. EM use was not associated with inpatient or ED visits in MV analysis. CONCLUSIONS: EM use was associated with improved glycemic control, even after controlling for electronic portal access and other variables, but not with hospitalizations or emergency visits. EM frequency was not associated with glycemic control, justifying the need for prospective studies. PMID- 27398825 TI - Paroxysmal Sympathetic Hyperactivity in a Child with Tuberculous Meningitis A Case Study and Review of Related Literature. AB - A one-year old boy was admitted to hospital for lethargy and vomiting over three days. Neurological examination revealed abnormalities. Cerebrospinal fluid examination showed evidence of meningitis. A purified protein derivative (PPD) test, T-SPOT.TB and radiological examination indicated tuberculous meningitis. During treatment, the child developed hypertension, sinus tachycardia, tachypnoea, dystonia and high fever. These episodes improved after administration of propranolol, artane and clonazepam. Paroxysmal sympathetic hyperactivity is a rare manifestation of tuberculous meningitis. Early detection is very important as it can avoid diagnostic errors and overtreatment. PMID- 27398826 TI - Stress, catecholaminergic system and cancer. AB - Stress as a modern civilization factor significantly affects our lives. While acute stress might have a positive effect on the organism, chronic stress is usually detrimental and might lead to serious health complications. It is known that stress induced by the physical environment (temperature-induced cold stress) can significantly impair the efficacy of cytotoxic chemotherapies and the anti tumor immune response. On the other hand, epidemiological evidence has shown that patients taking drugs known as beta-adrenergic antagonists ("beta-blockers"), which are commonly prescribed to treat arrhythmia, hypertension, and anxiety, have significantly lower rates of several cancers. In this review, we summarize the current knowledge about catecholamines as important stress hormones in tumorigenesis and discuss the use of beta-blockers as the potential therapeutic agents. PMID- 27398827 TI - The Impact of Age and Comorbidities on the Mortality of Patients of Different Age Groups Admitted with Community-acquired Pneumonia. AB - RATIONALE: Comorbidities, age, severity of illness, and high risk pathogens are well-known outcome determinants in community-acquired pneumonia (CAP). How these factors interact has not yet been clarified. OBJECTIVES: We conducted this study to analyze the complex interaction of comorbidities, age, illness severity, and pathogens in relation to CAP. METHODS: We performed a secondary analysis of the Community-Acquired Pneumonia Organization database to evaluate the impact of age in different age groups (<65, 65-79, and >=80 yr), comorbidities (malignant disease, chronic obstructive pulmonary disease, renal and liver disease, cerebrovascular accident, congestive heart failure, and diabetes mellitus), severity of illness at admission, and etiology on the mortality of patients admitted to the hospital with CAP. MEASUREMENTS AND MAIN RESULTS: A total of 6,205 patients met the inclusion criteria, and 508 (8.2%) died within 30 days. Factors independently associated with mortality were malignant disease, congestive heart failure, cerebrovascular accident, renal disease, diabetes mellitus, altered mental status, hypoxemia, pleural effusion, hematocrit less than 30%, requirement for mechanical ventilation, and being age 80 years and older. A total of 1,699 pathogens were defined in 1,545 cases; the etiology was the same for all age groups. In the overall population, mortality increased with age, but etiology was not associated with mortality. When we analyzed the patients with one comorbidity or less, we found that mortality was not different between patients younger than 65 old and those 65-79 years old, but it was higher for those aged 80 years and older. CONCLUSIONS: The presence of comorbidities is associated with poorer outcomes in CAP. However, when one comorbidity or less was present, we found that being age 80 years or older was a factor that increased mortality. From a clinical standpoint, this study suggests that being age 80 years or older, instead of age 65 years and older, should be considered a risk factor for poor outcome in CAP. PMID- 27398829 TI - Three-Dimensional Adhesion Map Based on Surface and Interfacial Cutting Analysis System for Predicting Adhesion Properties of Composite Electrodes. AB - Using a surface and interfacial cutting analysis system (SAICAS) that can measure the adhesion strength of a composite electrode at a specific depth from the surface, we can subdivide the adhesion strength of a composite electrode into two classes: (1) the adhesion strength between the Al current collector and the cathode composite electrode (FAl-Ca) and (2) the adhesion strength measured at the mid-depth of the cathode composite electrode (Fmid). Both adhesion strengths, FAl-Ca and Fmid, increase with increasing electrode density and loading level. From the SAICAS measurement, we obtain a mathematical equation that governs the adhesion strength of the composite electrodes. This equation revealed a maximum accuracy of 97.2% and 96.1% for FAl-Ca and Fmid, respectively, for four randomly chosen composite electrodes varying in electrode density and loading level. PMID- 27398828 TI - Feasibility of clinical psychosocial screening in pediatric oncology: Implementing the PAT2.0. AB - This study examined the feasibility of implementing the Psychosocial Assessment Tool (PAT2.0) from the perspectives of families and health-care providers (HCPs). PAT2.0 data were collected from 104 families. Individual and focus group interviews were conducted with HCPs. Parents reported that the PAT2.0 was brief and easy to complete. HCPs' perspectives on the utility of the PAT2.0 were mixed and varied according to clinical roles. A major perceived benefit was the PAT2.0 as a communication tool. Barriers included timing and an increased workload for social workers. Psychosocial screening represents a significant practice change for oncology HCPs and is an important area of ongoing research. PMID- 27398831 TI - Letter from the editor. PMID- 27398832 TI - Human Vaccines & Immunotherapeutics: News. PMID- 27398833 TI - Erratum. PMID- 27398834 TI - Erratum. PMID- 27398835 TI - PTEN regulates PLK1 and controls chromosomal stability during cell division. AB - PTEN functions as a guardian of the genome through multiple mechanisms. We have previously established that PTEN maintains the structural integrity of chromosomes. In this report, we demonstrate a fundamental role of PTEN in controlling chromosome inheritance to prevent gross genomic alterations. Disruption of PTEN or depletion of PTEN protein phosphatase activity causes abnormal chromosome content, manifested by enlarged or polyploid nuclei. We further identify polo-like kinase 1 (PLK1) as a substrate of PTEN phosphatase. PTEN can physically associate with PLK1 and reduce PLK1 phosphorylation in a phosphatase-dependent manner. We show that PTEN deficiency leads to PLK1 phosphorylation and that a phospho-mimicking PLK1 mutant causes polyploidy, imitating functional deficiency of PTEN phosphatase. Inhibition of PLK1 activity or overexpression of a non-phosphorylatable PLK1 mutant reduces the polyploid cell population. These data reveal a new mechanism by which PTEN controls genomic stability during cell division. PMID- 27398836 TI - Influence of Seasonal On-Farm Diversity on Dietary Diversity: A Case Study of Smallholder Farming Households in Western Kenya. AB - This study explored the associations between dietary patterns and farm diversity as well as socioeconomic variables during two seasons in rural Western Kenya. As a mean of two surveys, the average dietary diversity scores (DDS) of households and women were low, implying low household economic access to food and low women's dietary quality. The Food Consumption Score (FCS) showed that acceptable levels of food consumption were realized over seven consecutive days in the 2014 survey by the majority of households (83%) and women (90%). While there was no strong association between the food scores and seven farm diversity indicators, both food scores were significantly associated with the household's wealth status, ethnicity of both the household head and the spouse, and the education level of the spouse. For holistic household food and nutrition security approaches, we suggest a shift from a focus on farm production factors to incorporating easily overlooked socioeconomic factors such as household decision making power and ethnicity. PMID- 27398837 TI - The development of a measure of social cognition following acquired brain injury. AB - Deficits in social cognition following acquired brain injury (ABI) have been found to be both prevalent and disabling. Despite this, relatively little attention has been given to identifying the characteristics of such deficits in a systematic way. We describe the development of self and informant versions of a new questionnaire designed to measure the changes in social cognition that may occur following ABI, the Brain Injury Rehabilitation Trust (BIRT) Social Cognition Questionnaire (BSCQ). Seventy-two participants (Mean age = 36 years, SD = 12), with different forms of ABI (76% traumatic brain injury, 8% cerebrovascular accident, 15% other) and who were on average 20 months post injury (SD = 16), took part in the study. The measure demonstrates excellent psychometric properties, including high test-retest (.94) and split-half (.92) reliability, high internal consistency (Cronbach's alpha = .92), and good concurrent validity. The questionnaire measures characteristics that are distinguishable from measures of cognitive ability. There was moderate overlap between self-report and informant versions of the questionnaire (r = .50), but the informant version had the strongest predictive value of outcome, measured with the Mayo-Portland Adaptability Inventory III, one year later. The potential uses of the measure in relation to theory and practice are discussed. The results suggest that the BSCQ is a useful screening tool for those with ABI. PMID- 27398839 TI - Editor's notes. PMID- 27398838 TI - Specific tackling situations affect the biomechanical demands experienced by rugby union players. AB - Tackling in Rugby Union is an open skill which can involve high-speed collisions and is the match event associated with the greatest proportion of injuries. This study aimed to analyse the biomechanics of rugby tackling under three conditions: from a stationary position, with dominant and non-dominant shoulder, and moving forward, with dominant shoulder. A specially devised contact simulator, a 50-kg punch bag instrumented with pressure sensors, was translated towards the tackler (n = 15) to evaluate the effect of laterality and tackling approach on the external loads absorbed by the tackler, on head and trunk motion, and on trunk muscle activities. Peak impact force was substantially higher in the stationary dominant (2.84 +/- 0.74 kN) than in the stationary non-dominant condition (2.44 +/- 0.64 kN), but lower than in the moving condition (3.40 +/- 0.86 kN). Muscle activation started on average 300 ms before impact, with higher activation for impact-side trapezius and non-impact-side erector spinae and gluteus maximus muscles. Players' technique for non-dominant-side tackles was less compliant with current coaching recommendations in terms of cervical motion (more neck flexion and lateral bending in the stationary non-dominant condition) and players could benefit from specific coaching focus on non-dominant-side tackles. PMID- 27398840 TI - Letters. PMID- 27398841 TI - Scanning sports. PMID- 27398843 TI - Brief reports. PMID- 27398842 TI - Scuba Diving With MS. PMID- 27398844 TI - Running wild. PMID- 27398845 TI - Biorhythms and Sports. PMID- 27398846 TI - Rehabilitating the Injured Athlete. PMID- 27398847 TI - Rehabilitating the Injured Athlete. AB - The modem approach to rehabilitation is early mobilization and general reconditioning. The author outlines a program that begins with first aid on the athletic field and ends when the athlete returns to competition. PMID- 27398848 TI - Cme credit quiz no. 23. PMID- 27398849 TI - Use of Medications by US Olympic Swimmers. AB - As consultants to the United States Olympic Committee for Men's and Women's Swimming, the authors found that one-third of the Olympic swimming team had medications containing substances that could have disqualified them. PMID- 27398850 TI - Conservative Treatment of Plantar Fascial Strain. AB - Athletes in almost every sport are vulnerable to this painful and often frustratingly disabling disorder. A basic understanding of the anatomy, biomechanics, and pathophysiology is critical to effective conservative treatment. PMID- 27398851 TI - Are Athletic Trainers a Luxury or a Necessity? AB - A Northwestern University medical school program is putting athletic trainers into some high schools that never had them, but achieving that nationwide depends on some hard selling jobs on school boards-and physicians. PMID- 27398852 TI - High School Athletic Care Survey Reveals Improvement-and Inertia. PMID- 27398853 TI - EMTs Help to Solve High School Athletic Care Dilemma. PMID- 27398855 TI - Hip Abductors and Adductors in Rehabilitation. PMID- 27398857 TI - [Extradigital Glomus Tumor]. PMID- 27398858 TI - CROI 2016: Basic Science Review. AB - The 2016 Conference on Retroviruses and Opportunistic Infections continued to maintain balance in the representation of different areas of research related to HIV/AIDS. The basic science category encompasses research on viral reservoirs and HIV cure, on cellular factors regulating the interplay between virus and host, and on factors that influence viral pathogenicity. Basic research on factors that influence the interaction between the virus and the host cell continues to unearth surprises with the identification of a new host antiviral factor. Further, research into the mechanisms of viral persistence reveals that there is much to learn about how HIV-1 is able to persist in the face of antiviral suppression. PMID- 27398859 TI - CROI 2016: Hot Spots in HIV Infection and Advances in HIV Prevention. AB - The 2016 Conference on Retroviruses and Opportunistic Infections (CROI) highlighted hot spots in HIV infection. Men who have sex with men (MSM), transgender populations, people who inject drugs, fisherfolk, migrants, adolescents, and older adults are heavily impacted in a number of regions. Stigma contributes to risk behaviors and HIV acquisition across populations. HIV testing is a crucial first step in the HIV care continuum, and several large community based surveys are underway in Africa to increase HIV testing, linkage to care, and uptake of antiretroviral treatment. Advances in preexposure prophylaxis (PrEP) featured prominently at CROI 2016. Two large efficacy trials of a vaginal ring containing the investigational drug dapivirine demonstrated efficacy and safety in preventing HIV infections in women in Africa. Data on the safety of long-acting injectable PrEP and several investigational PrEP drugs and formulations were also presented. Knowledge and use of PrEP among MSM in the United States appears to be increasing, and high uptake was seen among black MSM when provided as part of a culturally tailored support program. The use of broadly neutralizing antibodies for HIV prevention is a novel and promising approach to be evaluated in efficacy trials. PMID- 27398860 TI - CROI 2016: Neurologic Complications of HIV Infection. AB - The brain remains a major target for HIV infection and a site of potential complications for HIV-infected individuals. Emerging data presented at the 2016 Conference on Retroviruses and Opportunistic Infections suggest that during the early stages of infection, activated CD4+ cells may traffic the virus into the central nervous system (CNS). HIV is detectable in cells and tissues of the CNS in some individuals despite suppressive antiretroviral treatment. A potential source of cerebrospinal fluid HIV escape may be compartmentalized HIV replication within macrophage lineage cells. Virally infected cells can traffic out of the CNS and may have the potential to reseed the systemic compartment. Additional modifiers of HIV-associated neurocognitive disorder (HAND) were identified, including female sex and hepatic dysfunction. Large epidemiologic studies reported an elevated risk of stroke among HIV-infected individuals, related to traditional vascular risk factors, history of recreational drug use, and HIV measures (lower CD4+ cell nadir and higher viral load). Brain imaging may provide a noninvasive means for detecting early changes in the brain associated with HIV infection and may assist in prognosis of HAND. Some potential adjunctive therapies to standard antiretroviral therapy for HIV-infected individuals were considered. PMID- 27398861 TI - CROI 2016: Complications of HIV Infection and Antiretroviral Therapy. AB - Noncommunicable conditions such as cardiovascular disease, hypertension, renal and bone diseases, and malignancies as well as infectious complications are an ongoing concern during the course of treated HIV disease. Research in this area continues to focus on the epidemiology and risk factors for these conditions, on identifying the contributions of HIV-related immunopathology to specific and collective end-organ diseases, and on evaluating interventions to prevent or reduce the morbidity associated with these conditions. Data presented at the 2016 Conference on Retroviruses and Opportunistic Infections provided new insights into all of these areas. PMID- 27398862 TI - CROI 2016: Viral Hepatitis and Liver Fibrosis. AB - At the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts, hepatitis C virus (HCV) infection remained a major theme in the context of HIV-associated liver disease, although other causes of liver disease garnered increased attention, including fatty liver disease, hepatitis B, and the impact of HIV disease itself on the liver. Although no data from phase III studies of HCV direct-acting antiviral (DAA) drugs for the treatment of HIV/HCV coinfection were presented at CROI 2016, a broad range of HCV DAA-related topics were presented, including accumulating experience with real-world performance of DAA-based regimens outside of clinical trials, drug interactions between DAA and antiretroviral drugs, treatment of acute HCV infection, and retreatment of individuals whose DAA-based regimens failed and those in whom resistance to DAA drugs emerged. A summary of select abstracts from CROI 2016 is presented, including discussion of clinical relevance where appropriate and areas for future research. PMID- 27398863 TI - CROI 2016: Advances in Antiretroviral Therapy. AB - The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID- 27398864 TI - Tin Ion Directed Morphology Evolution of Copper Sulfide Nanoparticles and Tuning of Their Plasmonic Properties via Phase Conversion. AB - Copper-deficient copper sulfide (Cu2-xS) nanoparticles (NPs) have been investigated as important hole-based plasmonic materials because of their size, morphology, and carrier density-dependent localized surface plasmon resonance (LSPR) properties. Morphology and carrier density are two important parameters to determine their LSPR properties. Here, we demonstrate that the foreign metal ion, Sn(4+), directs the growth of djurleite Cu31S16 from nanodisk to tetradecahedron along the [100] direction. To control the LSPR properties by tuning the carrier density, the djurleite Cu31S16 nanoparticles were pseudomorphically converted into more copper-deficient (higher carrier density) roxbyite Cu7S4 NPs by heat treatment in the presence of amine. The roxbyite Cu7S4 NPs exhibited a shorter and stronger LSPR peak while retaining the morphology of the djurleite Cu31S16 NPs. PMID- 27398866 TI - Quantifying Dimer and Trimer Formation by Tri-n-butyl Phosphates in n-Dodecane: Molecular Dynamics Simulations. AB - Tri-n-butyl phosphate (TBP), a representative of neutral organophosphorous ligands, is an important extractant used in the solvent extraction process for the recovery of uranium and plutonium from spent nuclear fuel. Microscopic pictures of TBP isomerism and its behavior in n-dodecane diluent were investigated utilizing MD simulations with previously optimized force field parameters for TBP and n-dodecane. Potential mean force (PMF) calculations on a single TBP molecule show seven probable TBP isomers. Radial distribution functions (RDFs) of TBP suggest the existence of TBP trimers at high TBP concentrations in addition to dimers. 2D PMF calculations were performed to determine the angle and distance criteria for TBP trimers. The dimerization and trimerization constants of TBP in n-dodecane were obtained and match our own experimental values using the FTIR technique. The new insights into the conformational behaviors of the TBP molecule as a monomer and as part of an aggregate could greatly aid in the understanding of the complexation between TBP and metal ions in a solvent extraction system. PMID- 27398867 TI - Predicting the Presence of Uncommon Elements in Unknown Biomolecules from Isotope Patterns. AB - The determination of the molecular formula is one of the earliest and most important steps when investigating the chemical nature of an unknown compound. Common approaches use the isotopic pattern of a compound measured using mass spectrometry. Computational methods to determine the molecular formula from this isotopic pattern require a fixed set of elements. Considering all possible elements severely increases running times and more importantly the chance for false positive identifications as the number of candidate formulas for a given target mass rises significantly if the constituting elements are not prefiltered. This negative effect grows stronger for compounds of higher molecular mass as the effect of a single atom on the overall isotopic pattern grows smaller. On the other hand, hand-selected restrictions on this set of elements may prevent the identification of the correct molecular formula. Thus, it is a crucial step to determine the set of elements most likely comprising the compound prior to the assignment of an elemental formula to an exact mass. In this paper, we present a method to determine the presence of certain elements (sulfur, chlorine, bromine, boron, and selenium) in the compound from its (high mass accuracy) isotopic pattern. We limit ourselves to biomolecules, in the sense of products from nature or synthetic products with potential bioactivity. The classifiers developed here predict the presence of an element with a very high sensitivity and high specificity. We evaluate classifiers on three real-world data sets with 663 isotope patterns in total: 184 isotope patterns containing sulfur, 187 containing chlorine, 14 containing bromine, one containing boron, one containing selenium. In no case do we make a false negative prediction; for chlorine, bromine, boron, and selenium, we make ten false positive predictions in total. We also demonstrate the impact of our method on the identification of molecular formulas, in particular on the number of considered candidates and running time. The element prediction will be part of the next SIRIUS release, available from https://bio.informatik.uni-jena.de/software/sirius/ . PMID- 27398868 TI - An Integrated Approach to Standard Methods, Materials, and Databases for the Measurements Used To Develop Surface Complexation Models. PMID- 27398872 TI - Tithonus Syndrome. PMID- 27398873 TI - Photosensitization of ZnO Crystals with Iodide-Capped PbSe Quantum Dots. AB - Lead selenide (PbSe) quantum dots (QDs) are an attractive material for application in photovoltaic devices due to the ability to tune their band gap, efficient multiple exciton generation, and high extinction coefficients. However, PbSe QDs are quite unstable to oxidation in air. Recently there have been multiple studies detailing postsynthetic halide treatments to stabilize lead chalcogenide QDs. We exploit iodide-stabilized PbSe QDs in a model QD-sensitized solar cell configuration where zinc oxide (ZnO) single crystals are sensitized using cysteine as a bifunctional linker molecule. Sensitized photocurrents stable for >1 h can be measured in aqueous KI electrolyte that is usually corrosive to QDs under illumination. The spectral response of the sensitization extended out to 1700 nm, the farthest into the infrared yet observed. Hints of the existence of multiple exciton generation and collection as photocurrent, as would be expected in this system, are speculated and discussed. PMID- 27398875 TI - The obesity penalty in the labor market using longitudinal Canadian data. AB - A Canadian study of weight discrimination also known as the obesity wage-penalty. This paper adds to the limited Canadian literature while also introducing a causal model, which can be applied to future Canadian studies. A general working class sample group is utilized with personal income, which removes many biases introduced in other studies. The evidence suggests that a 1-unit increase in lagged BMI is associated with a 0.7% decrease in personal for obese Canadian females. Similar to other studies, the male results are inconsistent. The evidence brought forward in this study can provide an effective financial incentive for health promotion among Canadians for law and policy makers. Beyond health reasons, these results can also be applied as empirical evidence of gender discrimination based on body image perception. The evidence suggests that male physique is not a contributing factor in income, but larger female physique is associated with lower personal income. PMID- 27398874 TI - Effectiveness of a Multicomponent Quality Improvement Strategy to Improve Achievement of Diabetes Care Goals: A Randomized, Controlled Trial. AB - BACKGROUND: Achievement of diabetes care goals is suboptimal globally. Diabetes focused quality improvement (QI) is effective but remains untested in South Asia. OBJECTIVE: To compare the effect of a multicomponent QI strategy versus usual care on cardiometabolic profiles in patients with poorly controlled diabetes. DESIGN: Parallel, open-label, pragmatic randomized, controlled trial. (ClinicalTrials.gov: NCT01212328). SETTING: Diabetes clinics in India and Pakistan. PATIENTS: 1146 patients (575 in the intervention group and 571 in the usual care group) with type 2 diabetes and poor cardiometabolic profiles (glycated hemoglobin [HbA1c] level >=8% plus systolic blood pressure [BP] >=140 mm Hg and/or low-density lipoprotein cholesterol [LDLc] level >=130 mg/dL). INTERVENTION: Multicomponent QI strategy comprising nonphysician care coordinators and decision-support electronic health records. MEASUREMENTS: Proportions achieving HbA1c level less than 7% plus BP less than 130/80 mm Hg and/or LDLc level less than 100 mg/dL (primary outcome); mean risk factor reductions, health-related quality of life (HRQL), and treatment satisfaction (secondary outcomes). RESULTS: Baseline characteristics were similar between groups. Median diabetes duration was 7.0 years; 6.8% and 39.4% of participants had preexisting cardiovascular and microvascular disease, respectively; mean HbA1c level was 9.9%; mean BP was 143.3/81.7 mm Hg; and mean LDLc level was 122.4 mg/dL. Over a median of 28 months, a greater percentage of intervention participants achieved the primary outcome (18.2% vs. 8.1%; relative risk, 2.24 [95% CI, 1.71 to 2.92]). Compared with usual care, intervention participants achieved larger reductions in HbA1c level (-0.50% [CI, -0.69% to -0.32%]), systolic BP (-4.04 mm Hg [CI, -5.85 to -2.22 mm Hg]), diastolic BP (-2.03 mm Hg [CI, -3.00 to -1.05 mm Hg]), and LDLc level (-7.86 mg/dL [CI, -10.90 to -4.81 mg/dL]) and reported higher HRQL and treatment satisfaction. LIMITATION: Findings were confined to urban specialist diabetes clinics. CONCLUSION: Multicomponent QI improves achievement of diabetes care goals, even in resource-challenged clinics. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and UnitedHealth Group. PMID- 27398876 TI - Individual health and the visibility of village economic inequality: Longitudinal evidence from native Amazonians in Bolivia. AB - Mounting evidence suggests that income inequality is associated with worse individual health. But does the visibility of inequality matter? Using data from a horticultural-foraging society of native Amazonians in Bolivia (Tsimane'), we examined whether village inequality in resources and behaviors with greater cultural visibility is more likely to bear a negative association with health than village inequality in less conspicuous resources. We draw on a nine-year annual panel (2002-2010) from 13 Tsimane' villages for our main analysis, and an additional survey to gauge the cultural visibility of resources. We measured inequality using the Gini coefficient. We tested the robustness of our results using a shorter two-year annual panel (2008-2009) in another 40 Tsimane' villages and an additional measure of inequality (coefficient of variation, CV). Behaviors with low cultural visibility (e.g., household farm area planted with staples) were less likely to be associated with individual health, compared to more conspicuous behaviors (e.g., expenditures in durable goods, consumption of domesticated animals). We find some evidence that property rights and access to resources matter, with inequality of privately-owned resources showing a larger effect on health. More inequality was associated with improved perceived health - maybe due to improved health prospects from increasing wealth - and worse anthropometric indicators. For example, a unit increase in the Gini coefficient of expenditures in durable goods was associated with 0.24 fewer episodes of stress and a six percentage-point lower probability of reporting illness. A one point increase in the CV of village inequality in meat consumption was associated with a 4 and 3 percentage-point lower probability of reporting illness and being in bed due to illness, and a 0.05 SD decrease in age-sex standardized arm-muscle area. In small-scale, rural societies at the periphery of market economies, nominal economic inequality in resources bore an association with individual health, but did not necessarily harm perceived health. Economic inequalities in small-scale societies apparently matter, but a thick cultural tapestry of reciprocity norms and kinship ties makes their effects less predictable than in industrial societies. PMID- 27398878 TI - The Elite Athlete and Strenuous Exercise in Pregnancy. AB - Highly trained women continue to exercise during pregnancy, but there is little information available to guide them, and their health care providers, in how to maximize performance without jeopardizing the maternal-fetal unit. Available evidence focusing on average women who perform regular vigorous exercise suggests that this activity is helpful in preventing several maladies of pregnancy, with little to no evidence of harm. However, some studies have shown that there may be a limit to how intense an elite performer should exercise during pregnancy. Health care providers should monitor these women athletes carefully, to build trust and understanding. PMID- 27398879 TI - Exercise in Pregnancy. PMID- 27398880 TI - Exercise in Pregnancy: Guidelines. AB - In recent years it has been recognized that in all phases of life, including pregnancy, physical activity promotes health benefits and precludes comorbidities, the scientific evidence is indisputable. Several organizations around the world have updated in recent years the guidelines and recommendations for exercise in pregnancy. The December 2015, updated guidelines of the American College of Obstetricians and Gynecologists emphasize that physical activity in pregnancy has minimal risk. Although recommending exercise in pregnancy, the anatomic/physiological changes, absolute and relative contraindications should be considered. Women who exercised regularly before pregnancy, in the absence of contraindications, can continue and engage in moderate to strenuous activities, although information on strenuous activities in pregnancy is still limited. This review summarizes the most recent published and recommended guidelines. PMID- 27398881 TI - The effect of self-reported health on latent herpesvirus reactivation and inflammation in an ethnically diverse sample. AB - Self-rated health (SRH) is a reliable predictor of health outcomes including morbidity and mortality. Immune dysregulation is one hypothesized mechanism underlying the association between SRH and health outcomes. Indeed, poorer SRH is associated with greater inflammation. The association between SRH and reactivation of latent herpesviruses is unknown, representing an important gap in the literature given that reactivation of latent herpesviruses leads to enhanced inflammation. The present study addressed this important gap in the literature by examining associations between SRH, inflammation (i.e., peripheral cytokines in the blood), and reactivation of latent herpesviruses among a sample of 1208 individuals participating in the Texas City Stress and Health Study. Participants completed a self-report measure of SRH and a blood draw. Results indicated that higher SRH was associated with lower reactivation of latent herpesviruses and inflammation. Moreover, reactivation of latent herpesviruses partially mediated the association between SRH and inflammation. Accordingly, findings add to our growing understanding of the association between SRH and immune dysfunction. PMID- 27398882 TI - Gonads and strife: Sex hormones vary according to sexual orientation for women and stress indices for both sexes. AB - This study assessed sexual orientation and psychobiological stress indices in relation to salivary sex hormones as part of a well-validated laboratory-based stress paradigm. Participants included 87 healthy adults that were on average 25 years old who self-identified as lesbian/bisexual women (n=20), heterosexual women (n=21), gay/bisexual men (n=26), and heterosexual men (n=20). Two saliva samples were collected fifteen minutes before and fifteen minutes after exposure to a modified Trier Social Stress Test to determine testosterone, estradiol, and progesterone concentrations via enzyme-immune assaying. Mean sex hormones were further tested in association to stress indices related to cortisol systemic output (area under the curve with respect to ground) based on ten measures throughout the two-hour visit, allostatic load indexed using 21 biomarkers, and perceived stress assessed using a well-validated questionnaire. Results revealed that lesbian/bisexual women had higher overall testosterone and progesterone concentrations than heterosexual women, while no differences were found among gay/bisexual men in comparison to heterosexual men. Lesbian/bisexual women and heterosexual men showed positive associations between mean estradiol concentrations and allostatic load, while gay/bisexual men and heterosexual women showed positive associations between mean testosterone and cortisol systemic output. In summary, sex hormone variations appear to vary according to sexual orientation among women, but also as a function of cortisol systemic output, allostatic load, and perceived stress for both sexes. PMID- 27398883 TI - Imaging the DNA Alkylator Melphalan by CEST MRI: An Advanced Approach to Theranostics. AB - Brain tumors are among the most lethal types of tumors. Therapeutic response variability and failure in patients have been attributed to several factors, including inadequate drug delivery to tumors due to the blood-brain barrier (BBB). Consequently, drug delivery strategies are being developed for the local and targeted delivery of drugs to brain tumors. These drug delivery strategies could benefit from new approaches to monitor the delivery of drugs to tumors. Here, we evaluated the feasibility of imaging 4-[bis(2-chloroethyl)amino]-l phenylalanine (melphalan), a clinically used DNA alkylating agent, using chemical exchange saturation transfer magnetic resonance imaging (CEST MRI), for theranostic applications. We evaluated the physicochemical parameters that affect melphalan's CEST contrast and demonstrated the feasibility of imaging the unmodified drug by saturating its exchangeable amine protons. Melphalan generated a CEST signal despite its reactivity in an aqueous milieu. The maximum CEST signal was observed at pH 6.2. This CEST contrast trend was then used to monitor therapeutic responses to melphalan in vitro. Upon cell death, the decrease in cellular pH from ~7.4 to ~6.4 caused an amplification of the melphalan CEST signal. This is contrary to what has been reported for other CEST contrast agents used for imaging cell death, where a decrease in the cellular pH following cell death results in a decrease in the CEST signal. Ultimately, this method could be used to noninvasively monitor melphalan delivery to brain tumors and also to validate therapeutic responses to melphalan clinically. PMID- 27398885 TI - Analysis of Associating Factors With C2-7 Sagittal Vertical Axis After Two-level Anterior Cervical Fusion: Comparison Between Plate Augmentation and Stand-alone Cages. AB - STUDY DESIGN: A retrospective review. OBJECTIVE: We investigated the longitudinal change of cervical alignment parameters including C2-7 lordosis, C2-7 sagittal vertical axis (SVA), T1 slope, and segmental angle (SA) after two-level anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Cervical alignment may influence postoperative clinical outcomes. Several studies have suggested that cervical alignment may serve as a parameter for assessing cervical deformities similar to those used to assess thoracolumbar spine deformities. However, to our knowledge, no studies have investigated the effect of ACDF on cervical sagittal alignment. METHODS: We enrolled patients whom had ACDF, 23 patients with stand-alone cages and 22 with plate augmentation. Radiologic parameters including C2-7 lordosis, C2-7 SVA, T1 slope, and SA at the operated level were evaluated preoperatively and at 1 week and 6 months postoperatively. The differences between preoperative and 6-month postoperative parameter values were designated as Deltavalues. T1S-CL was calculated as the T1 slope minus C2-7 lordosis. Clinical outcome were obtained by the Visual Analog Scale (VAS) and the Neck Disability Index (NDI). RESULTS: DeltaC2-7 SVA was significantly correlated with DeltaT1S-CL and DeltaC2-7 lordosis. DeltaC2-7 lordosis was significantly correlated with DeltaSA. DeltaC2-7 lordosis had a significantly greater impact on DeltaT1S-CL than did DeltaT1 slope. The DeltaSA and DeltaC2-7 lordosis in the ACDF-plate were significantly higher than those in the in ACDF-cage. DeltaT1S-CL and DeltaC2-7 SVA in the ACDF-plate were significantly lower than those in the ACDF-cage. CONCLUSION: C2-7 SVA after two-level ACDF was affected more significantly by the SA and C2-7 angle than by the T1 slope. Two-level ACDF with plate restored more cervical lordosis by obtaining more segmental lordosis at the operated level and was more effective in terms of cervical alignment compared with ACDF using stand-alone cages. LEVEL OF EVIDENCE: 3. PMID- 27398886 TI - Comparative Study of Surgical Treatment and Nonsurgical Follow Up for Thoracic Ossification of the Posterior Longitudinal Ligament: Radiological and Clinical Evaluation. AB - STUDY DESIGN: A prospective clinical study of factors related to myelopathy deterioration caused by thoracic myelopathy because of ossification of the posterior longitudinal ligament (T-OPLL). OBJECTIVE: The objective of the study was to investigate factors related to myelopathy deterioration caused by T-OPLL. SUMMARY OF BACKGROUND DATA: Detailed analyses of factors related to myelopathy deterioration caused by T-OPLL have not been reported. METHODS: Twenty-two patients (group O) received observation therapy because of the absence of or mild myelopathy, which was defined as walking unaided or with support, and a Japanese Orthopedic Association (JOA) score above 7 points; and 24 patients (group S) were treated with posterior decompression and fusion with instrumentation. Age, sex, body mass index (BMI), presence of diabetes mellitus (DM), and JOA score were obtained for all patients. Radiologically, the T-OPLL level, number of T-OPLLs, canal diameter ratio (CDR), morphology, ossification of the ligamentum flavum (OLF), and cervical OPLL were examined on reconstructed CT, and the presence of hyperintense areas (HIAs) on T2-weighted sagittal MR images. RESULTS: In total, the patients included 22 males and 24 females and had an age range from 18 to 80 years. Sex, DM, JOA score in each domain, OPLL location, OPLL number, CDR of OPLL, morphology, OLF, and cervical OPLL did not differ significantly between groups N and S. However, cases in group N had a significantly higher age, lower weight, lower BMI, lower discontinuous rate on sagittal CT, and a lower HIA rate on MRI. Postoperatively, discontinuous segments connected and became continuous across the disc space in all patients in group S without progression of OPLL thickness. CONCLUSION: Age, weight, BMI, discontinuity between rostral and caudal OPLL lesions, and occurrence of a high intensity area on MRI are likely to be associated with development of myelopathy. LEVEL OF EVIDENCE: 3. PMID- 27398887 TI - Advantages and Disadvantages of Adult Spinal Deformity Surgery and Its Impact on Health-Related Quality of Life. AB - STUDY DESIGN: Prospective multicenter study of adult spinal deformity (ASD) surgery. OBJECTIVE: To clarify the effect of ASD surgery on each health-related quality of life (HRQOL) subclass/domain. SUMMARY OF BACKGROUND DATA: For patients with ASD, surgery offers superior radiological and HRQOL outcomes compared with nonoperative care. HRQOL may, however, be affected by surgical advantages related to corrective effects, yielding adequate spinopelvic alignment and stability or disadvantages because of long segment fusion. METHODS: The study included 170 consecutive patients with ASD from a multicenter database with more than 2-year follow-up period. We analyzed each HRQOL domain/subclass (short form-36 items, Oswestry Disability Index, Scoliosis Research Society-22 [SRS-22] questionnaire), and radiographic parameters preoperatively and at 1 and 2 years postoperatively. We divided the patients into two groups each based on lowest instrumented vertebra (LIV; above L5 or S1 to ilium) or surgeon-determined preoperative pathology (idiopathic or degenerative). Improvement rate (%) was calculated as follows: 100 * |pre.-post.|/preoperative points (%) (+, advantages; -, disadvantages). RESULTS: The scores of all short form-36 items and SRS-22 subclasses improved at 1 and 2 years after surgery, regardless of LIV location and preoperative pathology. Personal care and lifting in Oswestry Disability Index were, however, not improved after 1 year. These disadvantages were correlated to sagittal modifiers of SRS-Schwab classification similar to other HRQOL. The degree of personal care disadvantage mainly depended on LIV location and preoperative pathology. Although personal care improved after 2 years postoperatively, no noticeable improvements in lifting were recorded. CONCLUSION: HRQOL subclass analysis indicated two disadvantages of ASD surgery, which were correlated to sagittal radiographic measures. Fusion to the sacrum or ilium greatly restricted the ability to stretch or bend, leading to limited daily activities for at least 1 year postoperatively, although this effect may subside after another year. Consequently, spinal surgeons should note the effect of surgical treatment on each HRQOL domain and counsel patients about the implications of surgery. LEVEL OF EVIDENCE: 4. PMID- 27398889 TI - Prolonged Perioperative Low-Dose Ketamine Does Not Improve Short and Long-term Outcomes After Pediatric Idiopathic Scoliosis Surgery. AB - STUDY DESIGN: A randomized, double-blind, placebo-controlled study, with a six month follow-up period. OBJECTIVES: The aim of this study was to test the hypothesis that a 72-hour dose of subanesthetic ketamine in this surgical procedure reduces postoperative morphine use and to assess whether there are fewer adverse effects, if postoperative recovery is faster, if there is less peri incisional hyperalgesia, or if there is lower incidence of persistent postsurgical pain. SUMMARY OF BACKGROUND DATA: Tissue injury and high opioid requirements following posterior spinal fusion surgery produce central sensitization, which can in turn be associated with hyperalgesia and chronic pain. Clinical trials involving this type of procedure using subanesthetic ketamine doses have assessed pain and morphine requirements with contradictory results. The effects of prolonged subanesthetic ketamine doses on postoperative recovery, mechanical hyperalgesia, and the incidence of chronic pain are unknown. METHODS: A total of 48 pediatric patients between 10 and 18 years diagnosed with idiopathic scoliosis were randomized to receive perioperative low-dose ketamine or placebo for 72 hours. They received general anesthesia, intraoperative remifentanil, and morphine postoperatively (patient-controlled analgesia). We measured morphine consumption, pain at rest and during movement (coughing), undesirable effects, and sedation during morphine treatment. The onset of oral intake, ambulation, and hospital stay were recorded. The extent of the peri incisional hyperalgesia was measured at 72 hours and pain controls were conducted postsurgery. RESULTS: Primary endpoint results (total cumulative morphine consumption while admitted) were obtained in 44 patients. Results were 2.72 (SD 1.13) in the placebo group and 3.13 (SD 1.13) in the study group (P = 0.2903), with no significant differences. Moreover, differences were not found between the experimental group and the placebo group in the secondary endpoints analyzed. CONCLUSION: Our findings do not support the routine combining of prolonged subanesthetic ketamine doses with opioids in posterior fusion surgery in children with idiopathic scoliosis. LEVEL OF EVIDENCE: 2. PMID- 27398890 TI - Perioperative Neurologic Complications in Adult Spinal Deformity Surgery: Incidence and Risk Factors in 564 Patients. AB - STUDY DESIGN: Prognostic study-case controlled. OBJECTIVE: Describe the rate of neurologic complications in adult spinal deformity surgery and describe the effect of these complications on clinical outcomes. SUMMARY OF BACKGROUND DATA: The incidence of neurologic complications and the risk factors for neurologic complications have not been reported in a large series of patients with adult spinal deformity (ASD). Existing series include a mixed patient cohort undergoing different types of spine surgery. METHODS: Patients with ASD undergoing surgery between 2008 and 2014 were analyzed. Patients with neurologic complications were identified; demographics, operative details, and radiographic and clinical outcomes were compared. A subanalysis of those with surgical and nonsurgical (e.g., stroke) neurologic complications was performed. Statistical analysis included t tests or chi tests as appropriate and a multivariate analysis. A P value of less than 0.025 was considered significant. RESULTS: A total of 564 patients met the inclusion criteria. The average age was 57 years. There were a total of 116 neurologic complications in 99 patients (17.6%). There were 88 surgical procedure-related neurologic complications in 77 patients (13.7%) and 28 nonsurgical neurologic complications in 28 patients (5.0%). The most common complications were radiculopathy (30%), motor deficits (22%), mental status changes (12%), and sensory deficits (12%). Revisions (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2-2.4) and interbody fusions (OR 2.1, 95% CI 1.4-3.2) were associated with an increased risk of neurologic complications. Decompression and osteotomies (including three-column osteotomies) did not increase the risk of neurologic complications. Patients with neurologic complications were not more likely to sustain other complications; however, they were more likely to undergo another operation during the follow-up period (OR 1.9, 95% CI 1.3-2.8). CONCLUSION: The overall incidence of neurologic complications in ASD surgery was 17.6%. The incidence of surgical neurologic complications was 13.7%. There was a higher risk of neurologic complications in revision cases and in cases in which interbody fusion was required. LEVEL OF EVIDENCE: 3. PMID- 27398891 TI - Impact of Depression and Bipolar Disorders on Functional and Quality of Life Outcomes in Patients Undergoing Surgery for Degenerative Cervical Myelopathy: Analysis of a Combined Prospective Dataset. AB - STUDY DESIGN: Analysis of a combined prospective dataset. OBJECTIVE: To compare clinical outcomes in patients with and without preexisting depression or bipolar disorder undergoing surgery for degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Psychiatric comorbidities, including depression, have been associated with worse clinical outcomes after lumbar spine surgery; however, it is unclear whether these psychiatric disorders are also predictive of outcomes in patients undergoing surgery for the treatment of DCM. METHODS: Four hundred and one patients with symptomatic DCM were enrolled in the prospective AOSpine International or North America study at twelve North American sites. Patients were evaluated preoperatively and at 6, 12, and 24 months using the modified Japanese Orthopedic Association scale (mJOA), Nurick score, Neck Disability Index (NDI), and Short- Form 36v2 (SF-36v2) Health Survey. A mixed model analytic approach was used to evaluate differences in outcomes at 24 months among patients with and without psychiatric disorders, while controlling for relevant baseline characteristics and surgical factors. RESULTS: Ninety-seven patients (24.19%) were diagnosed with preexisting depression or bipolar disorder. There were more females (65.98%) with these psychiatric disorders than males (34.02%) (P < 0.0001). Patients with psychiatric comorbidities were more likely to have cardiovascular (P = 0.0177), respiratory (P < 0.0001), gastrointestinal (P < 0.0001), rheumatologic (P = 0.0109), and neurologic (P = 0.0309) disorders. At 24 months after surgery, patients in both groups demonstrated significant improvements on the mJOA, Nurick, NDI, and SF-36v2 Physical Component Score (PCS). Patients with depression or bipolar disorder, however, did not exhibit a significant or clinically important change on the SF-36v2 Mental Component Score (MCS). There were no differences in mJOA and Nurick scores at 24 months among patients in each group. Improvement in NDI, SF-36v2 PCS, and MCS, however, were smaller in patients with depression or bipolar disorder than those without. CONCLUSION: Patients with depression or bipolar disorder have smaller functional and quality of life improvements after surgery compared to patients without psychiatric comorbidities. LEVEL OF EVIDENCE: 2. PMID- 27398892 TI - Most 30-day Readmissions After Anterior Cervical Discectomy and Fusion Are Not Due to Surgical Site-Related Issues: An Analysis of 17,088 Patients. AB - STUDY DESIGN: A retrospective study of patients undergoing anterior cervical discectomy and fusion (ACDF) in the prospective National Surgical Quality Improvement Program (NSQIP) database. OBJECTIVE: To determine the most common reasons for readmission within 30 days after elective ACDF. SUMMARY OF BACKGROUND DATA: ACDF is a commonly performed surgery that is safe and effective for treating a variety of cervical spine pathologies. With new quality-based reimbursements tied to readmissions within 30 days of discharge, better understanding of the causes of readmissions is, however, needed. METHODS: Patients undergoing ACDF in the NSQIP database from 2012 to 2014 were reviewed. The overall rate of readmission and documented reasons for readmission were collected. Multivariate regression was then used to determine risk factors for readmissions. RESULTS: A total of 17,088 patients undergoing elective ACDF were identified. There were 545 (3.2%) readmissions within 30 postoperative days. Of the readmitted patients, 293 (53.8%) were readmitted for nonsurgical site-related reasons, with neuropsychiatric (n = 44), cardiovascular (n = 39), and pneumonia (n = 37) being the most common reasons. A total of 184 patients (33.8%) were readmitted for surgical site-related reasons, with surgical site infection (n = 42), hemorrhage/hematoma (n = 42), and dysphagia (n = 32) being the most common reasons. A total of 84 patients (15.6%) had undocumented reasons for readmission. In multivariate analysis, only older age and higher American Society of Anesthesiologists class were independently associated with readmissions. CONCLUSION: Most readmissions after ACDF were due to nonsurgical site-related reasons, suggesting the importance of careful patient selection, aggressive preoperative medical optimization, and adequate postoperative management. LEVEL OF EVIDENCE: 3. PMID- 27398895 TI - Does the Traversing Length of the Aorta Change After Closing Wedge Osteotomy for Ankylosing Spondylitis Patients With Thoracolumbar Kyphosis?: A Magnetic Resonance Imaging Investigation. AB - STUDY DESIGN: A prospective magnetic resonance imaging (MRI) study. OBJECTIVE: To investigate the change in aortic traversing length in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) after closing wedge osteotomy (CWO). SUMMARY OF BACKGROUND DATA: The CWO has been widely adopted for the correction of thoracolumbar kyphosis caused by AS. During this procedure, the aorta may be elongated in the instrumented area, which implies a potential risk of the aortic injury. To date, no reports have been specifically published using MRI to investigate the alteration in aortic traversing length in patients with AS undergoing CWO. METHODS: From June 2013 to July 2015, 24 patients with AS with thoracolumbar kyphosis with a mean age of 38.1 years were recruited in the present study. All patients underwent single-level CWO. MRI examinations were performed before and 2 weeks after surgery. For each subject, the aortic diameter and length were measured on the MRI. Radiographic measurements included the global kyphosis, thoracic kyphosis, lumbar lordosis, local kyhosis, angle of fusion levels, and anterior height of the osteotomized vertebra. The height of these patients was also recorded. RESULTS: The aortic traversing length significantly increased by an average of 2.0 cm after surgery. Significant changes in height, global kyphosis, lumbar lordosis, local kyphosis, and angle of fusion levels were observed (P < 0.01), whereas the anterior height of the osteotomized vertebra was comparable before and after surgery (P > 0.05). In addition, the correlation analysis revealed a significant correlation between the aortic traversing length and changes in global kyphosis, lumbar lordosis, local kyphosis, angle of fusion levels, and height (P < 0.01). CONCLUSION: The stretch of the aorta after CWO for the correction of thoracolumbar kyphosis was quantitatively verified by MRI investigation in the present study. Spine surgeons should be aware of the potential vulnerability of aortic injury in patients with AS undergoing CWO. LEVEL OF EVIDENCE: 4. PMID- 27398896 TI - Indications and Outcomes of Cell Saver in Adolescent Scoliosis Correction Surgery: A Systematic Review. AB - STUDY DESIGN: Systematic review. OBJECTIVE: The aim of this study was to determine the indications and outcomes for intraoperative cell salvage during adolescent scoliosis correction surgery by systematically reviewing all available evidence. SUMMARY OF BACKGROUND DATA: Several blood conservation strategies exist to minimize the consequences of blood loss because of scoliosis correction surgery. The utility of intraoperative cell salvage has been contested in the literature with respect to benefits and cost. High-quality randomized control trials are needed to help surgeons make an informed decision about including Cell Saver into their practice. METHODS: The databases Medline, Embase, Ovid Healthstar, and PubMed were searched for English language literature investigating Cell Saver use during adolescent scoliosis correction surgery, mean ages 10 to 19 years inclusively. Qualitative and quantitative findings from relevant studies are presented. RESULTS: There were seven eligible studies that directly compared the use of Cell Saver (349 patients) against a Control (non Cell Saver) group (244 patients). The majority of the demographic and hematologic data were consistent between both groups. The average volume of blood that was re infused into patients in the Cell Saver group was 453.8 mL. Patients in the Cell Saver group received significantly fewer allogenic blood transfusions than the Control group, with 32.6% less intraoperatively, 45.9% less postoperatively, and 47.3% less perioperatively. On average, Cell Saver patients received 1.0 fewer unit of allogenic blood compared to the Control group patients. CONCLUSION: Cell Saver reduces the demand for allogenic transfusion. This review supports the use of Cell Saver if the associated monetary costs are expected to be less than the cost of transfusing one unit of allogenic blood. LEVEL OF EVIDENCE: 4. PMID- 27398897 TI - Minimally Invasive Robotic Versus Open Fluoroscopic-guided Spinal Instrumented Fusions: A Randomized Controlled Trial. AB - STUDY DESIGN: A prospective randomized clinical trial. OBJECTIVE: To compare the impact of robotic guidance in a minimally invasive spine surgery (MIS) to a fluoroscopy-guided open approach in lumbar fusions. SUMMARY OF BACKGROUND DATA: MIS requires a protracted learning curve and excessively exposes the patient and surgical team to harmful radiation. Robotic-guidance has been shown to improve accuracy and radiation in most studies, but there is conflicting prospective data. METHODS: Patients indicated to undergo a 1 or 2 level spinal fusion were randomized between robotic-guided MIS (RO) and fluoroscopic-guided open surgery (FA). Patient demographics and outcomes were recorded. RESULTS: Thirty patients were recruited to each arm. Average age was 66.7 years, 71.5% were females, and average body mass index was 25.2. Thirty-five levels were instrumented with 130 pedicle screws in RO versus 40 levels with 140 screws in FA, or 4.3 and 4.7 screws per surgery, respectively. Use of fluoroscopy was 3.5 versus 13.3 seconds in the RO and FA respectively (P < 0.001). C-arm output in mSv was 0.13 versus 0.27 in the RO and FA respectively (P = 0.015). By thermoluminescent dosimeters, the average per-screw radiation in the RO arm was 37.5% of that in the FA arm, demonstrating a mean reduction of 62.5% in use of radiation. There was no difference in the improvement in Visual Analog Scale scores for back and leg or the Oswestry Disability Index. All screws were accurate in RO whereas two screws breached (>2 mm and >4 mm) in FA (P = 0.500). One proximal facet violation occurred in the study, it was in FA (P = 1.000). The average distance from the proximal facets was 5.8 versus 4.6 mm in the RO and FA respectively (P < 0.001). The average length of stay was 6.8 versus 9.4 days in RO compared with FA (P = 0.020). CONCLUSION: MIS using robotic-guidance significantly reduced radiation exposure and length of stay. Patient outcomes were not affected by the surgical technique. LEVEL OF EVIDENCE: 1. PMID- 27398899 TI - Feasibility of Posterior Cervical Foraminotomy in Cervical Foraminal Stenosis: Prediction of Surgical Outcomes by the Foraminal Shape on Preoperative Computed Tomography. AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was to compare the feasibility of posterior cervical laminoforaminotomy (PCF) for V- or parallel-shaped foraminal stenosis (FS). SUMMARY OF BACKGROUND DATA: During PCF, the need for extensive facet resection would depend on the extent of any pathology. When resection is extensive, the possibilities of instability and incomplete decompression should be considered. METHODS: From March 2004 to March 2015, we enrolled 36 patients following single-level PCF procedures for FS. We classified patients by foraminal shape on preoperative computed tomography (CT) scan into V-shaped and parallel-shaped groups. We then compared arm and neck pain using a numeric rating scale (NRS) and clinical outcomes using Odom criteria. Radiological evaluation included dynamic X-rays for instability and CT scans for facet resection. RESULT: We enrolled 16 and 20 patients in the V-shape and parallel-shape groups, respectively. By Odom criteria, no patient was graded fair or poor in the V group, but five patients were graded as fair and one patient as poor in the parallel group. Continued postoperative arm pain at 1 year, which was related to incomplete decompression, was significantly higher in parallel group. Only one patient complained of postoperative neck pain with an NRS >5, and another five patients sustained radiculopathy with an NRS >5. Among five patients who complained sustained radiculopathy, one patient required revision surgery for incomplete decompression. The amount of facet removal was not different significantly between groups, and no patient had postoperative instability. CONCLUSION: Although PCF seems to be a good surgical option for V-shaped FS, we experienced worse outcomes for patients with parallel-shaped FS. We recommend that ACDF or more aggressive posterior foraminotomy be performed with fusion when presented with parallel neuroforaminal compression. LEVEL OF EVIDENCE: 4. PMID- 27398900 TI - Temporary Iliac Fixation to Salvage an Acute L4 Chance Fracture: Following Pedicle Screw Fixation for Adolescent Idiopathic Scoliosis. AB - STUDY DESIGN: A case report. OBJECTIVE: The aim of this study was to describe a technique of temporary distal fixation to the ilium to salvage an acute L4 fracture following a T3-L4 kyphoscoliosis correction. SUMMARY OF BACKGROUND DATA: Pedicle fracture is a possible complication in pedicle screw fixation for scoliosis, which may lead to postoperative instability, resulting in loss of fixation and pseudoarthrosis. This report highlights the salvage treatment of a chance fracture that occurred in the lower instrumented vertebra following deformity correction for adolescent idiopathic scoliosis (AIS) without sacrificing further distal motion segments. METHODS: A retrospective chart and radiograph review of a 13-year-old female who underwent surgical treatment for correction of AIS was performed. RESULTS: Following a T3-L4 correction with apical posterior column releases, an L4 Chance fracture with loss of distal fixation occurred on post-op day 3. Following an unsuccessful salvage with an infralaminar hook, a second revision was performed replacing the hook and adding bilateral temporary fixation to the ilium connected to the distal ends of the main rods through side-to-side connectors. The temporary fixation was removed 6 months later with successful healing of the fracture maintenance of the scoliosis correction at 2-year follow-up. CONCLUSION: Temporary extension of the construct to the ilium was successfully utilized in this case to salvage an acute L4 Chance fracture that occurred following a T3 to L4 construct for kyphoscoliosis. With this technique, successful reduction and healing of the fracture occurred with maintenance of the deformity correction without the need to fuse further distal segments. LEVEL OF EVIDENCE: 4. PMID- 27398902 TI - Response to the Letter to the Editor. PMID- 27398903 TI - Effort in emotion work and well-being: The role of goal attainment. AB - It is well established that regulating one's emotion display in social settings entails psychological costs such as lower well-being. However, regulating emotion display may also help achieving goals, and goal attainment is known to enhance well-being. We therefore investigated the hypothesis that success in attaining goals during social interactions would reduce the negative impact of regulatory effort on well-being. In an experience sampling study, 115 Swiss employees reported their social encounters for 7 consecutive days. For each interaction, participants were asked to report their effort in regulating their emotions, their level of goal attainment, and their momentary well-being after the interaction. Data being nested (Level 1: interactions; Level 2: person), multilevel analyses were conducted. Continuous level 1 predictors were group mean centered, implying that their effects on well-being were strictly intraindividual. Gender, age, extraversion, and neuroticism were controlled on the person level, the context of the interaction (private vs. work) as well as positive and negative emotions felt during the social encounter were controlled on the situation level. Analysis of 1,674 social interactions containing a goal confirmed that regulatory effort predicted lower well-being after social interactions (Hypothesis 1), that degree of goal attainment predicted better well being after these interactions (Hypothesis 2), and that degree of goal attainment buffered the negative effect of effort (Hypothesis 3). Research and theory should pay more attention to the fact that emotions often are regulated in the service of goals, and that attaining these goals may, at least partially, compensate for the effort invested. (PsycINFO Database Record PMID- 27398904 TI - Felt power explains the link between position power and experienced emotions. AB - The approach/inhibition theory by Keltner, Gruenfeld, and Anderson (2003) predicts that powerful people should feel more positive and less negative emotions. To date, results of studies investigating this prediction are inconsistent. We fill this gap with four studies in which we investigated the role of different conceptualizations of power: felt power and position power. In Study 1, participants were made to feel more or less powerful and we tested how their felt power was related to different emotional states. In Studies 2, 3, and 4, participants were assigned to either a high or a low power role and engaged in an interaction with a virtual human, after which participants reported on how powerful they felt and the emotions they experienced during the interaction. We meta-analytically combined the results of the four studies and found that felt power was positively related to positive emotions (happiness and serenity) and negatively to negative emotions (fear, anger, and sadness), whereas position power did not show any significant overall relation with any of the emotional states. Importantly, felt power mediated the relationship between position power and emotion. In summary, we show that how powerful a person feels in a given social interaction is the driving force linking the person's position power to his or her emotional states. (PsycINFO Database Record PMID- 27398905 TI - Positive emotion, appraisal, and the role of appraisal overlap in positive emotion co-occurrence. AB - Appraisal research has traditionally focused on negative emotions but has not addressed issues concerning the relationships between several positive emotions and appraisals in daily life and the extent to which co-occurrence of positive emotions can be explained by overlap in appraisals. Driven by a priori hypotheses on appraisal-emotion relationships, this study investigated 12 positive emotions and 13 appraisal dimensions using Ecological Momentary Assessment. The results provide strong evidence that positive emotions and appraisals correlate significantly in daily life. Importantly, we found that the positive emotions' overlap on theoretically relevant, as compared to irrelevant, appraisals was stronger and more predictive of their co-occurrence. Furthermore, appraisal overlap on theoretically relevant appraisals predicted the co-occurrence of positive emotions even when the appraisal of pleasantness was excluded, indicating that positive emotions do not co-occur just by virtue of their shared valence. Our findings affirmed and refined the appraisal profiles of positive emotions and underscore the importance of appraisals in accounting for the commonality and differences among positive emotions. (PsycINFO Database Record PMID- 27398906 TI - Synthesis, spectroscopic and computational studies of 2-(thiophen-2-yl)-2,3 dihydro-1H-perimidine: An enzymes inhibition study. AB - The biologically relevant molecule; 2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine was synthesized and characterized by FT-IR, UV, 1H and 13C NMR, MS, CHN microanalysis, X-ray crystallography as well as by theoretical, B3LYP/6 311++G(d,p), calculations. The vibrational bands appearing in the FT-IR were assigned with great accuracy using animated modes. Molecular properties like HOMO LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural charges have been presented at the same level of theory. The theoretical results are found in good correlation with the experimental data obtained from the various spectral techniques. Moreover, the Hirshfeld analysis was performed to explore the secondary interactions and associated 2D fingerprint plots. Perimidine molecule displayed promising inhibitory activity against acetylcholinesterase (AChE) as compared to the reference drug, tacrine. Molecular docking was carried out to ascertain the synthesized molecule into the X-ray crystal structures of acetylcholinesterase at the active site to find out the probable binding mode. The results of molecular docking admitted that perimidine may reveal enzyme inhibitor activity. PMID- 27398907 TI - Soil inoculation steers restoration of terrestrial ecosystems. AB - Many natural ecosystems have been degraded because of human activities(1,2) and need to be restored so that biodiversity is protected. However, restoration can take decades and restoration activities are often unsuccessful(3) because of abiotic constraints (for example, eutrophication, acidification) and unfavourable biotic conditions (for example, competition or adverse soil community composition). A key question is what manageable factors prevent transition from degraded to restored ecosystems and what interventions are required for successful restoration(2,4). Experiments have shown that the soil community is an important driver of plant community development(5-8), suggesting that manipulation of the soil community is key to successful restoration of terrestrial ecosystems(3,9). Here we examine a large-scale, six-year-old field experiment on ex-arable land and show that application of soil inocula not only promotes ecosystem restoration, but that different origins of soil inocula can steer the plant community development towards different target communities, varying from grassland to heathland vegetation. The impact of soil inoculation on plant and soil community composition was most pronounced when the topsoil layer was removed, whereas effects were less strong, but still significant, when the soil inocula were introduced into intact topsoil. Therefore, soil inoculation is a powerful tool to both restore disturbed terrestrial ecosystems and steer plant community development. PMID- 27398908 TI - Auditing Practice Style Variation in Pediatric Inpatient Asthma Care. AB - IMPORTANCE: Asthma is the most prevalent chronic illness among children, remaining a leading cause of pediatric hospitalizations and representing a major financial burden to many health care systems. OBJECTIVE: To implement a new auditing process examining whether differences in hospital practice style may be associated with potential resource savings or inefficiencies in treating pediatric asthma admissions. DESIGN, SETTING, AND PARTICIPANTS: A retrospective matched-cohort design study, matched for asthma severity, compared practice patterns for patients admitted to Children's Hospital Association hospitals contributing data to the Pediatric Hospital Information System (PHIS) database. With 3 years of PHIS data on 48 887 children, an asthma template was constructed consisting of representative children hospitalized for asthma between April 1, 2011, and March 31, 2014. The template was matched with either a 1:1, 2:1, or 3:1 ratio at each of 37 tertiary care children's hospitals, depending on available sample size. EXPOSURE: Treatment at each PHIS hospital. MAIN OUTCOMESS AND MEASURES: Cost, length of stay, and intensive care unit (ICU) utilization. RESULTS: After matching patients (n = 9100; mean [SD] age, 7.1 [3.6] years; 3418 [37.6%] females) to the template (n = 100, mean [SD] age, 7.2 [3.7] years; 37 [37.0%] females), there was no significant difference in observable patient characteristics at the 37 hospitals meeting the matching criteria. Despite similar characteristics of the patients, we observed large and significant variation in use of the ICUs as well as in length of stay and cost. For the same template-matched populations, comparing utilization between the 12.5th percentile (lower eighth) and 87.5th percentile (upper eighth) of hospitals, median cost varied by 87% ($3157 vs $5912 per patient; P < .001); total hospital length of stay varied by 47% (1.5 vs 2.2 days; P < .001); and ICU utilization was 254% higher (6.5% vs 23.0%; P < .001). Furthermore, the patterns of resource utilization by patient risk differed significantly across hospitals. For example, as patient risk increased one hospital displayed significantly increasing costs compared with their matched controls (comparative cost difference: lowest risk, 34.21%; highest risk, 53.27%; P < .001). In contrast, another hospital displayed significantly decreasing costs relative to their matched controls as patient risk increased (comparative cost difference: lowest risk, -10.12%; highest risk, 16.85%; P = .01). CONCLUSIONS AND RELEVANCE: For children with asthma who had similar characteristics, we observed different hospital resource utilization; some values differed greatly, with important differences by initial patient risk. Through the template matching audit, hospitals and stakeholders can better understand where this excess variation occurs and can help to pinpoint practice styles that should be emulated or avoided. PMID- 27398909 TI - Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. AB - Tissue mechanics drive morphogenesis, but how forces are sensed and transmitted to control stem cell fate and self-organization remains unclear. We show that a mechanosensory complex of emerin (Emd), non-muscle myosin IIA (NMIIA) and actin controls gene silencing and chromatin compaction, thereby regulating lineage commitment. Force-driven enrichment of Emd at the outer nuclear membrane of epidermal stem cells leads to defective heterochromatin anchoring to the nuclear lamina and a switch from H3K9me2,3 to H3K27me3 occupancy at constitutive heterochromatin. Emd enrichment is accompanied by the recruitment of NMIIA to promote local actin polymerization that reduces nuclear actin levels, resulting in attenuation of transcription and subsequent accumulation of H3K27me3 at facultative heterochromatin. Perturbing this mechanosensory pathway by deleting NMIIA in mouse epidermis leads to attenuated H3K27me3-mediated silencing and precocious lineage commitment, abrogating morphogenesis. Our results reveal how mechanics integrate nuclear architecture and chromatin organization to control lineage commitment and tissue morphogenesis. PMID- 27398912 TI - A Novel-Design Poly-L-Lactic Acid Biodegradable Device for Closure of Atrial Septal Defect: Long-Term Results in Swine. AB - OBJECTIVES: The aim of this study is to evaluate the long-term effectiveness and safety of a self-expandable, double-disk biodegradable device made of poly-L lactic acid (PLLA) for closure of atrial septal defects (ASDs) in swine. METHODS: ASDs were created by transseptal needle puncture followed by balloon dilatation in 20 piglets. The experimental group comprised 18 animals, while the remaining 2 animals were used as controls. Effectiveness and safety were evaluated by rectal temperature, leukocyte count, chest radiography, electrocardiogram, transthoracic echocardiography (TTE), intracardiac echocardiography (ICE), and histologic studies. Animals were followed up at 1, 3, 6, and 12 months. RESULTS: An ASD model was successfully created in 19 animals; 1 piglet died during the procedure. The ASD diameters that were created ranged from 5 to 6.4 mm. Devices were successfully implanted in 17 animals. No animal died during the follow-up studies. Rectal temperatures and electrocardiograms were normal at follow-up, while leukocyte counts transiently increased from 1 to 6 months. Radiography, TTE, ICE, and macroscopic studies demonstrated that PLLA occluders were positioned well, with no shifting, mural thrombus formation, or atrioventricular valve insufficiency. Histologic evaluations showed that PLLA devices were partially degraded in the follow-up study. CONCLUSIONS: ASD closure with the novel PLLA biodegradable device is safe and effective. Longer-term studies are needed to evaluate long-term biodegradability. PMID- 27398913 TI - Internal and External Match Loads of University-Level Soccer Players: A Comparison Between Methods. AB - Sparks, M, Coetzee, B, and Gabbett, TJ. Internal and external match loads of university-level soccer players: a comparison between methods. J Strength Cond Res 31(4): 1072-7077, 2017-The aim of this study was to use individualized intensity zones to compare the external (velocity and player load, PL) and internal loads (heart rate, HR) of a cohort of university-level soccer players. Thirteen soccer players completed a 40-m maximum speed test and the Yo-Yo intermittent recovery test 1 (Yo-Yo IR1) to determine individualized velocity and HR thresholds. Heart rate values and global positioning system (GPS) data of each player were recorded during 5 league matches. A large (r = 0.46; p <= 0.01) correlation was found between time spent in the low-intensity (LI) velocity zone (LIVZ) and the LI HR zone. Similarly, there were moderate (r = 0.25; p <= 0.01) to large (r = 0.57; p <= 0.01) correlations between the relative and absolute time spent in the moderate-intensity (MI) velocity zone (MIVZ) and the MI HR zone. No significant correlations (p <= 0.01) existed between the high-intensity (HI) velocity zones (HIVZ) and the HI HR zone. On the other hand, PL showed significant correlations with all velocity and HR (absolute and relative) variables, with the exception of a nonsignificant correlation between the HI HR variables and PL. To conclude, PL showed good correlations with both velocity and HR zones and therefore may have the potential to serve as a good indicator of both external and internal soccer match loads. PMID- 27398911 TI - Cathepsin-B-mediated cleavage of Disabled-2 regulates TGF-beta-induced autophagy. AB - Transforming growth factor-beta (TGF-beta) induces the expression of Disabled-2 (Dab2), an endocytic adaptor and tumour suppressor, concomitant with the induction of an epithelial-mesenchymal transition (EMT) in mammary epithelial cells. Here we show that following TGF-beta-mediated EMT, sustained TGF-beta treatment leads to proteolytic degradation of Dab2 by cathepsin B (CTSB), loss of the mesenchymal phenotype and induction of autophagy. CTSB inhibition or expression of a CTSB-resistant Dab2 mutant maintains Dab2 expression and shifts long-term TGF-beta-treated cells from autophagy to apoptosis. We further show that Dab2 interacts with Beclin-1 to promote casein-kinase-2-mediated phosphorylation of Beclin-1, preventing Beclin-1-Vps34 interaction and subsequent autophagosome assembly. Thus, CTSB-mediated degradation of Dab2 allows Beclin-1 Vps34 induction of autophagy, whereas sustained Dab2 expression prevents autophagy and promotes apoptosis by stabilizing the pro-apoptotic Bim protein. In vivo studies suggest that Dab2-mediated regulation of autophagy modulates chemotherapeutic resistance and tumour metastasis. PMID- 27398914 TI - Comparison of Three Timing Systems: Reliability and Best Practice Recommendations in Timing Short-Duration Sprints. AB - Bond, CW, Willaert, EM, and Noonan, BC. Comparison of three timing systems: reliability and best practice recommendations in timing short-duration sprints. J Strength Cond Res 31(4): 1062-1071, 2017-With the importance placed on athletic speed, it is important to use a valid and reliable timing system, particularly in sprints of short duration. Unfortunately, many of the commonly used timing systems have not been rigorously evaluated. This study aimed to compare results from a single-beam infrared photocell (PC), single-beam laser with a microprocessor (LA), and a previously validated video camera (VC) sacrum-based timing system; and in doing so, determine these systems' reliabilities, and establish best practices for increasing reliability. It was hypothesized that PC and LA times would be different from VC times and show reduced reliability compared with VC. Fifteen athletes performed 5 repetitions of a 60-foot maximal effort sprint with split times recorded for the first and second half. Photocell and LA full-time and first-half split times were significantly slower than VC (p < 0.001), but almost identical for the second half split (p = 0.08). Repeated sprint analysis showed that VC tended to have smaller SD compared with PC and LA for first-half split (0.05 vs. 0.08 vs. 0.09 seconds, respectively) and total time (0.09 vs. 0.10 vs. 0.11 seconds, respectively). Time differences were more dependent on initial forward lean and varying body segments triggering the beam, than on a systematic instrument error. The increased variability of PC and LA systems dampen the ability to determine whether meaningful change has occurred. The VC system allows for very valid and reliable measurements of an athlete's sprint time, especially in distances <30 feet. PMID- 27398910 TI - Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL. AB - Phosphoinositides (PtdIns) control fundamental cell processes, and inherited defects of PtdIns kinases or phosphatases cause severe human diseases, including Lowe syndrome due to mutations in OCRL, which encodes a PtdIns(4,5)P2 5 phosphatase. Here we unveil a lysosomal response to the arrival of autophagosomal cargo in which OCRL plays a key part. We identify mitochondrial DNA and TLR9 as the cargo and the receptor that triggers and mediates, respectively, this response. This lysosome-cargo response is required to sustain the autophagic flux and involves a local increase in PtdIns(4,5)P2 that is confined in space and time by OCRL. Depleting or inhibiting OCRL leads to an accumulation of lysosomal PtdIns(4,5)P2, an inhibitor of the calcium channel mucolipin-1 that controls autophagosome-lysosome fusion. Hence, autophagosomes accumulate in OCRL-depleted cells and in the kidneys of Lowe syndrome patients. Importantly, boosting the activity of mucolipin-1 with selective agonists restores the autophagic flux in cells from Lowe syndrome patients. PMID- 27398915 TI - Effects of Cold Water Immersion and Contrast Water Therapy for Recovery From Team Sport: A Systematic Review and Meta-analysis. AB - Higgins, TR, Greene, DA, Baker, MK. Effects of cold water immersion and contrast water therapy for recovery from team sport: a systematic review and meta analysis. J Strength Cond Res 31(5): 1443-1460, 2017-To enhance recovery from sport, cold water immersion (CWI) and contrast water therapy (CWT) have become common practice within high level team sport. Initially, athletes relied solely on anecdotal support. As there has been an increase in the volume of research into recovery including a number of general reviews, an opportunity existed to narrow the focus specifically examining the use of hydrotherapy for recovery in team sport. A Boolean logic [AND] keyword search of databases was conducted: SPORTDiscus; AMED; CINAHL; MEDLINE. Data were extracted and the standardized mean differences were calculated with 95% confidence interval (CI). The analysis of pooled data was conducted using a random-effect model, with heterogeneity assessed using I. Twenty-three peer reviewed articles (n = 606) met the criteria. Meta-analyses results indicated CWI was beneficial for recovery at 24 hours (countermovement jump: p = 0.05, CI: -0.004 to 0.578; All-out sprint: p = 0.02, 0.056 to 0.801) following team sport. The CWI was beneficial for recovery at 72 hours (fatigue: p = 0.03, CI: 0.061-1.418) and CWT was beneficial for recovery at 48 hours (fatigue: p = 0.04, CI: 0.013-0.942) following team sport. The CWI was beneficial for neuromuscular recovery 24 hours following team sport, whereas CWT was not beneficial for recovery following team sport. In addition, when evaluating accumulated sprinting, CWI was not beneficial for recovery following team sports. In evaluating subjective measures, both CWI (72 hours) and CWT (24 hours) were beneficial for recovery of perceptions of fatigue, following team sport. However neither CWI nor CWT was beneficial for recovery, of perceptions of muscle soreness, following team sport. PMID- 27398916 TI - The Physical and Athletic Performance Characteristics of Division I Collegiate Female Soccer Players by Position. AB - Lockie, RG, Moreno, MR, Lazar, A, Orjalo, AJ, Giuliano, DV, Risso, FG, Davis, DL, Crelling, JB, Lockwood, JR, and Jalilvand, F. The physical and athletic performance characteristics of Division I collegiate female soccer players by position. J Strength Cond Res 32(2): 334-343, 2018-Playing positions in soccer can exhibit different movement demands during a match, contributing to variations in physical and performance characteristics. National Collegiate Athletic Association (NCAA) soccer features different substitution rules when compared to FIFA-sanctioned matches, which could influence each players' characteristics. Therefore, this study determined the athletic performance characteristics of Division I female soccer players. Twenty-six players (3 goalkeepers; 8 defenders; 10 midfielders; 5 forwards) from the same squad completed assessments of: lower body power (vertical and standing broad jump); linear (0-5, 0-10, 0-30 meter [m] sprint intervals) and change-of-direction (pro-agility shuttle; arrowhead change of-direction speed test) speed; and soccer-specific fitness (Yo-Yo Intermittent Recovery Test [YYIRT] levels 1 and 2). Players were split into position groups, and a Kruskal-Wallis H test with post hoc pairwise analyses (p <= 0.05) calculated significant between-group differences. There were no differences in age, height, or body mass between the positions. Midfielders had a faster 0-5 m time compared with the defenders (p = 0.017) and the goalkeepers (p = 0.030). The defenders (p = 0.011) and midfielders (p = 0.013) covered a greater YYIRT2 distance compared with the goalkeepers. There were no other significant between position differences. Overall, Division I collegiate female players from the same squad demonstrated similar characteristics as measured by soccer-specific performance tests, which could allow for flexibility in position assignments. However, a relatively homogenous squad could also indicate commonality in training prescription, particularly regarding acceleration and high-intensity running. Strength and conditioning coaches may have to consider the specific movement demands of individual positions when training these capacities. PMID- 27398917 TI - Full Range of Motion Induces Greater Muscle Damage Than Partial Range of Motion in Elbow Flexion Exercise With Free Weights. AB - Baroni, BM, Pompermayer, MG, Cini, A, Peruzzolo, AS, Radaelli, R, Brusco, CM, and Pinto, RS. Full range of motion induces greater muscle damage than partial range of motion in elbow flexion exercise with free weights. J Strength Cond Res 31(8): 2223-2230, 2017-Load and range of motion (ROM) applied in resistance training (RT) affect the muscle damage magnitude and the recovery time-course. Because exercises performed with partial ROM allow a higher load compared with those with full ROM, this study investigated the acute effect of a traditional RT exercise using full ROM or partial ROM on muscle damage markers. Fourteen healthy men performed 4 sets of 10 concentric-eccentric repetitions of unilateral elbow flexion on the Scott bench. Arms were randomly assigned to partial-ROM (50-100 degrees ) and full-ROM (0-130 degrees ) conditions, and load was determined as 80% of 1 repetition maximum (1RM) in the full- and partial-ROM tests. Muscle damage markers were assessed preexercise, immediately, and 24, 48, and 72 hours after exercise. Primary outcomes were peak torque, muscle soreness during palpation and elbow extension, arm circumference, and joint ROM. The load lifted in the partial-ROM condition (1RM = 19.1 +/- 3.0 kg) was 40 +/- 18% higher compared with the full-ROM condition (1RM = 13.7 +/- 2.2 kg). Seventy-two hours after exercise, the full-ROM condition led to significant higher soreness sensation during elbow extension (1.3-4.1 cm vs. 1.0-1.9 cm) and smaller ROM values (97.5-106.1 degrees vs. 103.6-115.7 degrees ). Peak torque, soreness from palpation, and arm circumference were statistically similar between conditions, although mean values in all time points of these outcomes have suggested more expressive muscle damage for the full-ROM condition. In conclusion, elbow flexion exercise with full ROM seems to induce greater muscle damage than partial-ROM exercises, even though higher absolute load was achieved with partial ROM. PMID- 27398918 TI - The Effects of the Gaelic Athletic Association 15 Training Program on Neuromuscular Outcomes in Gaelic Football and Hurling Players: A Randomized Cluster Trial. AB - O'Malley, E, Murphy, JC, McCarthy Persson, U, Gissane, C, and Blake, C. The effects of the Gaelic Athletic Association 15 training program on neuromuscular outcomes in Gaelic football and hurling players: A randomized cluster trial. J Strength Cond Res 31(8): 2119-2130, 2017-Team-based neuromuscular training programs for injury prevention have been tested primarily in female and adolescent athletes in soccer, handball, and basketball with limited research in adult male field sports. This study explored whether the GAA 15, a multifaceted 8 week neuromuscular training program developed by the Gaelic Athletic Association (GAA), could improve risk factors for lower limb injury in male Gaelic footballers and hurlers. Four Gaelic sports collegiate teams were randomized into intervention or control groups. Two teams (n = 41), one football and one hurling, were allocated to the intervention, undertaking a 15 minutes program of neuromuscular training exercises at the start of team training sessions, twice weekly for 8 weeks. Two matched teams (n = 37) acted as controls, participating in usual team training. Lower extremity stability (Y-Balance test [YBT]) and jump landing technique using the Landing Error Scoring System (LESS) were assessed preintervention and postintervention. There were moderate effect sizes in favor of the intervention for right (d = 0.59) and left (d = 0.69) composite YBT scores, with adjusted mean differences between intervention and control of 3.85 +/- 0.91% and 4.34 +/- 0.92% for right and left legs, respectively (p < 0.001). There was a greater reduction in the mean LESS score in favor of the intervention group after exercise training (Cohen's d = 0.72, adjusted mean difference 2.49 +/ 0.54, p < 0.001). Clinically and statistically significant improvements in dynamic balance and jump-landing technique occurred in collegiate level Gaelic football and hurling players who adopted the GAA 15, when compared with usual training. These findings support application and evaluation of the GAA 15 in other player groups within the Gaelic games playing population. PMID- 27398919 TI - Comparison of Anthropometry and Lower Limb Power Qualities According to Different Levels and Ranking Position of Competitive Surfers. AB - Fernandez-Gamboa, I, Yanci, J, Granados, C, and Camara, J. Comparison of anthropometry and lower limb power qualities according to different levels and ranking position of competitive surfers. J Strength Cond Res 31(8): 2231-2237, 2017-The aim of this study was to compare competitive surfers' lower limb power output depending on their competitive level, and to evaluate the association between competition rankings. Twenty competitive surfers were divided according to the competitive level as follows: international (INT) or national (NAT), and competitive ranking (RANK1-50 or RANK51-100). Vertical jump and maximal peak power of the lower limbs were measured. No differences were found between INT and NAT surfers in the anthropometric variables, in the vertical jump, or in lower extremity power; although the NAT group had higher levels on the elasticity index, squat jumps (SJs), and counter movement jumps (CMJs) compared with the INT group. The RANK1-50 group had a lower biceps skinfold (p < 0.01), lower skinfolds in the legs (Front thigh: p <= 0.05; medial calf: p < 0.01), lower sum of skinfolds (p <= 0.05), higher SJ (p < 0.01), CMJ (p < 0.01), and 15 seconds vertical CMJ (p <= 0.05); also, maximal peak power of the right leg (MPPR) and left leg (MPPL) were higher in the RANK1-50 group. Moderate to large significant correlations were obtained between the surfers' ranking position and some skinfolds, the sum of skinfolds, and vertical jump. Results demonstrate that surfers' physical performance seems to be an accurate indicator of ranking positioning, also revealing that vertical jump capacity and anthropometric variables play an important role in their competitive performance, which may be important when considering their power training. PMID- 27398920 TI - Vertical- vs. Horizontal-Oriented Drop Jump Training: Chronic Effects on Explosive Performances of Elite Handball Players. AB - Dello Iacono, A, Martone, D, Milic, M, and Padulo, J. Vertical- vs. horizontal oriented drop jump training: chronic effects on explosive performances of elite handball players. J Strength Cond Res 31(4): 921-931, 2017-This study aimed to assess the chronic effects of vertical drop jump (VDJ)- and horizontal drop jump (HDJ)-based protocols on neuromuscular explosive abilities, such as jumping, sprinting, and changes of direction (COD). Eighteen elite male handball players (age 23.4 +/- 4.6 years, height 192.5 +/- 3.7 cm, weight 87.8 +/- 7.4 kg) were assigned to either VDJ or HDJ group training twice a week for 10 weeks. Participants performed 5-8 sets * 6-10 repetitions of vertical alternate (VDJ) or horizontal alternate (HDJ) 1-leg drop jumps, landing from the top of a platform 25 cm in height. Before and after training, several performance, kinetic, and kinematic variables were assessed. The HDJ led to greater improvement of the sprint time (-8.5% vs. -4%, p <= 0.05) and COD performance in comparison with the VDJ (-7.9% vs. -1.1%, p <= 0.05), whereas the VDJ caused greater improvement in the vertical jump compared with the HDJ (+8.6% vs. +4.1%, p <= 0.05). Moreover, the VDJ regimen compared with the HDJ induced greater changes in the kinetic variables associated with vertical jumping performance, such as peak ground reaction forces (+10.3% vs. +4.3%), relative impulse (+12.4% vs. +5.7%), leg spring stiffness (+17.6% vs. +4.6%), contact time (CT) (-10.1% vs. -1.5%), and reactive strength index (+7.2% vs. +2.1%); all comparisons with p <= 0.05. Conversely, the HDJ regimen was able to improve the short-distance and COD performances by increasing the step length (+3.5% vs. +1.5% with p <= 0.05) and reducing the CT on COD (-12.1% vs. -2.1% with p <= 0.05) more than the VDJ. This investigation showed the crucial role that specific plyometric regimens play in optimizing similar biomechanical featured functional performances, such as jumping, sprinting, and COD. PMID- 27398921 TI - Is Moderate Intensity Cycling Sufficient to Induce Cardiorespiratory and Biomechanical Modifications of Subsequent Running? AB - Walsh, JA, Dawber, JP, Lepers, R, Brown, M, and Stapley, PJ. Is moderate intensity cycling sufficient to induce cardiorespiratory and biomechanical modifications of subsequent running? J Strength Cond Res 31(4): 1078-1086, 2017 This study sought to determine whether prior moderate intensity cycling is sufficient to influence the cardiorespiratory and biomechanical responses during subsequent running. Cardiorespiratory and biomechanical variables measured after moderate intensity cycling were compared with control running at the same intensity. Eight highly trained, competitive triathletes completed 2 separate exercise tests; (a) a 10-minute control run (no prior cycling) and, (b) a 30 minute transition run (TR) (preceded by 20-minute of variable cadence cycling, i.e., run versus cycle-run). Respiratory, breathing frequency (fb), heart rate (HR), cost of running (Cr), rate constant, stride length, and stride frequency variables were recorded, normalized, and quantified at the mean response time (MRT), third minute, 10th minute (steady state), and overall for the control run (CR) and TR. Cost of running increased (p <= 0.05) at all respective times during the TR. The V[Combining Dot Above]E/V[Combining Dot Above]CO2 and respiratory exchange ratio (RER) were significantly (p < 0.01) elevated at the MRT and 10th minute of the TR. Furthermore, overall mean increases were recorded for Cr, V[Combining Dot Above]E, V[Combining Dot Above]E/V[Combining Dot Above]CO2, RER, fb (p < 0.01), and HR (p <= 0.05) during the TR. Rate constant values for oxygen uptake were significantly different between CR and TR (0.48 +/- 0.04 vs. 0.89 +/- 0.15; p < 0.01). Stride length decreased across all recorded points during the TR (p <= 0.05) and stride frequency increased at the MRT and 3 minutes (p < 0.01). The findings suggest that at moderate intensity, prior cycling influences the cardiorespiratory response during subsequent running. Furthermore, prior cycling seems to have a sustained effect on the Cr during subsequent running. PMID- 27398922 TI - Aerial Rotation Effects on Vertical Jump Performance Among Highly Skilled Collegiate Soccer Players. AB - Barker, LA, Harry, JR, Dufek, JS, and Mercer, JA. Aerial rotation effects on vertical jump performance among highly skilled collegiate soccer players. J Strength Cond Res 31(4): 932-938, 2017-In soccer matches, jumps involving rotations occur when attempting to head the ball for a shot or pass from set pieces, such as corner kicks, goal kicks, and lob passes. However, the 3 dimensional ground reaction forces used to perform rotational jumping tasks are currently unknown. Therefore, the purpose of this study was to compare bilateral, 3-dimensional, and ground reaction forces of a standard countermovement jump (CMJ0) with those of a countermovement jump with a 180 degrees rotation (CMJ180) among Division-1 soccer players. Twenty-four participants from the soccer team of the University of Nevada performed 3 trials of CMJ0 and CMJ180. Dependent variables included jump height, downward and upward phase times, vertical (Fz) peak force and net impulse relative to mass, and medial-lateral and anterior posterior force couple values. Statistical significance was set a priori at alpha = 0.05. CMJ180 reduced jump height, increased the anterior-posterior force couple in the downward and upward phases, and increased upward peak Fz (p <= 0.05). All other variables were not significantly different between groups (p > 0.05). However, we did recognize that downward peak Fz trended lower in the CMJ0 condition (p = 0.059), and upward net impulse trended higher in the CMJ0 condition (p = 0.071). It was concluded that jump height was reduced during the rotational jumping task, and rotation occurred primarily via AP ground reaction forces through the entire countermovement jump. Coaches and athletes may consider additional rotational jumping in their training programs to mediate performance decrements during rotational jump tasks. PMID- 27398923 TI - Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System. AB - BACKGROUND: Melatonin has been shown to have antidepressive effects. We tested whether melatonin inhibits the acid sphingomyelinase/ceramide system and mediates its antidepressive effects via inhibition of the acid sphingomyelinase and a reduction of ceramide in the hippocampus. Antidepressants such as amitriptyline and fluoxetine were previously shown to inhibit the acid sphingomyelinase/ceramide system, which mediates neurogenesis and behavioral changes induced by these drugs. METHODS: The effect of melatonin on the activity of the acid sphingomyelinase prior to and after treatment with melatonin was determined in cultured neurons and in vivo in the hippocampus of mice by measuring the consumption of [14C] sphingomyelin. Ceramide was measured by DAG kinase assay and fluorescence microscopy of the hippocampus and of cultured neurons. Neurogenesis in the hippocampus was analyzed by in vivo labeling with bromodeoxyuridine. Behavior was assessed in standardized tests. RESULTS: Melatonin treatment inhibited acid sphingomyelinase in vitro in cultured pheochromocytoma cells and in vivo in the hippocampus, which resulted in a reduction of ceramide in vitro and in vivo. The inhibition of the acid sphingomyelinase/ceramide system translated into increased neurogenesis in glucocorticosterone-stressed mice after treatment with melatonin, an effect that is abrogated in acid sphingomyelinase-deficient mice. Likewise, melatonin improved the depressive behavior of stressed mice, a therapeutic effect that was again absent in acid sphingomyelinase-deficient animals. CONCLUSION: These data indicate that the antidepressive effects of melatonin as well as the induction of neurogenesis triggered by this drug are mediated by an inhibition of the acid sphingomyelinase/ceramide system. This is the first study to identify melatonin as an inhibitor of the acid sphingomyelinase. PMID- 27398924 TI - What is the thermal conductivity limit of silicon germanium alloys? AB - The lowest possible thermal conductivity of silicon-germanium (SiGe) bulk alloys achievable through alloy scattering, or the so-called alloy limit, is important to identify for thermoelectric applications. However, this limit remains a subject of contention as both experimentally-reported and theoretically-predicted values tend to be widely scattered and inconclusive. In this work, we present a possible explanation for these discrepancies by demonstrating that the thermal conductivity can vary significantly depending on the degree of randomness in the spatial arrangement of the constituent atoms. Our study suggests that the available experimental data, obtained from alloy samples synthesized using ball milling techniques, and previous first-principles calculations, restricted by small supercell sizes, may not have accessed the alloy limit. We find that low frequency anharmonic phonon modes can persist unless the spatial distribution of Si and Ge atoms is completely random at the atomic scale, in which case the lowest possible thermal conductivity may be achieved. Our theoretical analysis predicts that the alloy limit of SiGe could be around 1-2 W m(-1) K(-1) with an optimal composition around 25 at% Ge, which is substantially lower than previously reported values from experiments and first-principles calculations. PMID- 27398925 TI - Electrically Tunable Harmonic Generation of Light from Plasmonic Structures in Electrolytes. AB - An emerging trend in plasmonics is to exploit nanostructured metals as a self contained electrooptic platform with simultaneously supported electrical and optical functions. When it comes to nonlinear optics, this dual electrical and optical functionality offers an exciting potential to enable electrically controlled wave mixing processes in various nanometallic systems. Here we demonstrate tunable nonlinear generation of light enabled by an electrically active plasmonic crystal in aqueous electrolytic solutions. A modulation depth of ~150%/V is observed in the second-harmonic signal, thanks to the light concentrating ability of the resonant plasmonic structure as well as the voltage assisted charge accumulation on the metallic surfaces. The hybrid plasmonic electrolyte system demonstrated in this work offers the exciting new potential to use plasmonic nanostructures for voltage-controlled nonlinear signal generation and in situ biochemical sensing in an aqueous environment. PMID- 27398926 TI - Competitive Ring Expansion of Azetidines into Pyrrolidines and/or Azepanes. AB - Azetidines fitted with a 3-hydroxypropyl side chain at the 2-position undergo intramolecular N-alkylation after activation of the primary alcohol, and the produced 1-azonia-bicyclo[3.2.0]heptane is opened by different nucleophiles (cyanide, azide, or acetate anions) to produce mixtures of ring expanded pyrrolidines and azepanes, or a unique type of compound. Distribution of produced five- or seven-membered rings depends on the substitution pattern on the azetidine ring and on its side chain, together with the nature of the nucleophile used in the expansion process. Observed regioselectivities for nucleophilic opening are rationalized by quantum mechanical DFT calculations and are in good agreement with experimental results. PMID- 27398929 TI - Error in Figure Labeling. PMID- 27398931 TI - Assessing Aromatic-Hydrocarbon Toxicity to Fish Early Life Stages Using Passive Dosing Methods and Target-Lipid and Chemical-Activity Models. AB - Aromatic hydrocarbons (AH) are known to impair fish early life stages (ELS). However, poorly defined exposures often confound ELS-test interpretation. Passive dosing (PD) overcomes these challenges by delivering consistent, controlled exposures. The objectives of this study were to apply PD to obtain 5 d acute embryo lethality and developmental data and 30 d chronic embryo-larval survival and growth-effects data using zebrafish with different AHs; to analyze study and literature toxicity data using target-lipid (TLM) and chemical-activity (CA) models; and to extend PD to a mixture and test the assumption of AH additivity. PD maintained targeted exposures over a concentration range of 6 orders of magnitude. AH toxicity increased with log Kow up to pyrene (5.2). Pericardial edema was the most sensitive sublethal effect that often preceded embryo mortality, although some AHs did not produce developmental effects at concentrations causing mortality. Cumulative embryo-larval mortality was more sensitive than larval growth, with acute-to-chronic ratios of <10. More hydrophobic AHs did not exhibit toxicity at aqueous saturation. The relationship and utility of the TLM-CA models for characterizing fish ELS toxicity is discussed. Application of these models indicated that concentration addition provided a conservative basis for predicting ELS effects for the mixture investigated. PMID- 27398932 TI - Relationship between Fetuin A, Vascular Calcification and Fracture Risk in Dialysis Patients. AB - BACKGROUND: Fractures are a common morbidity that lead to worse outcomes in dialysis patients. Fetuin A inhibits vascular calcification (VC), potentially promotes bone mineralization and its level positively correlates with bone mineral density in the general population. On the other hand, the presence of VC is associated with low bone volume in dialysis patients. Whether the fetuin A level and VC can predict the occurrence of fractures in dialysis patients remains unknown. METHODS: We performed this prospective, observational cohort study including 685 dialysis patients (629 hemodialysis and 56 peritoneal dialysis) from a single center in Taiwan for a median follow-up period of 3.4 years. The baseline fetuin A level and status of presence of aortic arch calcification (VC) and incidence of major fractures (hip, pelvis, humerus, proximal forearm, lower leg or vertebrae) were assessed using adjusted Cox proportional hazards models, recursive partitioning analysis and competing risk models. RESULTS: Overall, 177 of the patients had major fractures. The incidence rate of major fractures was 3.29 per 100 person-years. In adjusted analyses, the patients with higher baseline fetuin A levels had a lower incidence of fractures (adjusted hazard ratio (HR), 0.3; 95% CI, 0.18-0.5, fetuin A tertile 3 vs. tertile 1 and HR, 0.52; 95% CI, 0.34-0.78, tertile 2 vs. tertile 1). The presence of aortic arch calcification (VC) independently predicted the occurrence of fractures (adjusted HR, 1.95; 95% CI, 1.34-2.84) as well. When accounting for death as an event in competing risk models, the patients with higher baseline fetuin A levels remained to have a lower incidence of fractures (SHR, 0.31; 95% CI, 0.17-0.56, fetuin A tertile 3 vs. tertile 1 and 0.51; 95% CI, 0.32-0.81, tertile 2 vs. tertile 1). INTERPRETATIONS: Lower baseline fetuin A levels and the presence of VC were independently linked to higher risk of incident fractures in prevalent dialysis patients. PMID- 27398934 TI - On the existence of intramolecular one-electron Be-Be bonds. AB - Although the Be-Be bond is extremely weak in Be2 dimers, we have shown that rather stable Be-Be one-electron sigma bonds are formed upon electron attachment to 1,8-diBeX-naphthalene derivatives. Wavefunction analyses corroborate the formation of Be-Be covalent linkages in which the extra electron is accommodated between the Be atoms as reflected in the dramatic shortening of the Be-Be distance with respect to the corresponding neutral molecule. PMID- 27398933 TI - The Xanthomonas campestris pv. vesicatoria Type-3 Effector XopB Inhibits Plant Defence Responses by Interfering with ROS Production. AB - The bacterial pathogen Xanthomonas campestris pv. vesicatoria 85-10 (Xcv) translocates about 30 type-3 effector proteins (T3Es) into pepper plants (Capsicum annuum) to suppress plant immune responses. Among them is XopB which interferes with PTI, ETI and sugar-mediated defence responses, but the underlying molecular mechanisms and direct targets are unknown so far. Here, we examined the XopB-mediated suppression of plant defence responses in more detail. Infection of susceptible pepper plants with Xcv lacking xopB resulted in delayed symptom development compared to Xcv wild type infection concomitant with an increased formation of salicylic acid (SA) and expression of pathogenesis-related (PR) genes. Expression of xopB in Arabidopsis thaliana promoted the growth of the virulent Pseudomonas syringae pv. tomato (Pst) DC3000 strain. This was paralleled by a decreased SA-pool and a lower induction of SA-dependent PR gene expression. The expression pattern of early flg22-responsive marker genes indicated that MAPK signalling was not altered in the presence of XopB. However, XopB inhibited the flg22-triggered burst of reactive oxygen species (ROS). Consequently, the transcript accumulation of AtOXI1, a ROS-dependent marker gene, was reduced in xopB-expressing Arabidopsis plants as well as callose deposition. The lower ROS production correlated with a low level of basal and flg22-triggered expression of apoplastic peroxidases and the NADPH oxidase RBOHD. Conversely, deletion of xopB in Xcv caused a higher production of ROS in leaves of susceptible pepper plants. Together our results demonstrate that XopB modulates ROS responses and might thereby compromise plant defence. PMID- 27398936 TI - Tumor dormancy and frailty models: A novel approach. AB - Frailty models are here proposed in the tumor dormancy framework, in order to account for possible unobservable dependence mechanisms in cancer studies where a non-negligible proportion of cancer patients relapses years or decades after surgical removal of the primary tumor. Relapses do not seem to follow a memory less process, since their timing distribution leads to multimodal hazards. From a biomedical perspective, this behavior may be explained by tumor dormancy, i.e., for some patients microscopic tumor foci may remain asymptomatic for a prolonged time interval and, when they escape from dormancy, micrometastatic growth results in a clinical disease appearance. The activation of the growth phase at different metastatic states would explain the occurrence of metastatic recurrences and mortality at different times (multimodal hazard). We propose a new frailty model which includes in the risk function a random source of heterogeneity (frailty variable) affecting the components of the hazard function. Thus, the individual hazard rate results as the product of a random frailty variable and the sum of basic hazard rates. In tumor dormancy, the basic hazard rates correspond to micrometastatic developments starting from different initial states. The frailty variable represents the heterogeneity among patients with respect to relapse, which might be related to unknown mechanisms that regulate tumor dormancy. We use our model to estimate the overall survival in a large breast cancer dataset, showing how this improves the understanding of the underlying biological process. PMID- 27398935 TI - Two-Step Regulation of a Meristematic Cell Population Acting in Shoot Branching in Arabidopsis. AB - Shoot branching requires the establishment of new meristems harboring stem cells; this phenomenon raises questions about the precise regulation of meristematic fate. In seed plants, these new meristems initiate in leaf axils to enable lateral shoot branching. Using live-cell imaging of leaf axil cells, we show that the initiation of axillary meristems requires a meristematic cell population continuously expressing the meristem marker SHOOT MERISTEMLESS (STM). The maintenance of STM expression depends on the leaf axil auxin minimum. Ectopic expression of STM is insufficient to activate axillary buds formation from plants that have lost leaf axil STM expressing cells. This suggests that some cells undergo irreversible commitment to a developmental fate. In more mature leaves, REVOLUTA (REV) directly up-regulates STM expression in leaf axil meristematic cells, but not in differentiated cells, to establish axillary meristems. Cell type-specific binding of REV to the STM region correlates with epigenetic modifications. Our data favor a threshold model for axillary meristem initiation, in which low levels of STM maintain meristematic competence and high levels of STM lead to meristem initiation. PMID- 27398937 TI - Profound clinical and radiological response to BRAF inhibition in a 2-month-old diencephalic child with hypothalamic/chiasmatic glioma. AB - Infants with low-grade glioma (LGG) have a poor survival. BRAFV600E mutation has been identified in pediatric LGG; however, the use of BRAF inhibitors in infants has never been reported. A 2-month-old with V600E mutant hypothalamic/chiasmatic glioma progressed on chemotherapy resulting in profound visual loss, massive ascites, and diencephalic syndrome. Initiation of dabrafenib resulted in rapid and sustained disappearance of clinical symptoms and a profound sustained cytoreduction. BRAF inhibition was safely tolerated with dramatic clinicoradiological response, suggesting early targeted therapy is a viable option in infants with LGG. A re-evaluation of current management paradigms in this population is warranted to leverage the potential benefit of upfront targeted therapies. PMID- 27398939 TI - Evidence of a bacterial core in the stored products pest Plodia interpunctella: the influence of different diets. AB - The potential influence of insects' feeding behaviour on their associated bacterial communities is currently a matter of debate. Using the major pest of commodities, Plodia interpunctella, as a model and adopting a culture-independent approach, the impact of different diets on the host-associated microbiota was evaluated. An analysis of similarity showed differences among the microbiotas of moths fed with five substrates and provided evidence that diet represents the only tested factor that explains this dissimilarity. Bacteria shared between food and insects provide evidence for a limited conveyance to the host of the bacteria derived from the diet; more likely, the content of carbohydrates and proteins in the diets promotes changes in the insect's microbiota. Moth microbiotas were characterized by two robust entomotypes, respectively, associated with a carbohydrate-rich diet and a protein-rich diet. These results were also confirmed by the predicted metagenome functional potential. A core microbiota, composed of six taxa, was shared between eggs and adults, regardless of the origin of the population. Finally, the identification of possible human and animal pathogens on chili and associated with the moths that feed on it highlights the possibility that these bacteria may be conveyed by moth frass. PMID- 27398940 TI - Can the Medical-nursing Combined Care Promote the Accessibility of Health Services for the Elderly in Nursing Home? A Study Protocol of Analysis of the Effectiveness Regarding Health Service Utilization, Health Status and Satisfaction with Care. AB - Background: Currently, segmentation of healthcare and daily care for the elderly living in nursing homes usually results in the elderly not getting medical treatment timely and effectively. The medical-nursing combined care, which has been put into practice in several areas in China, is developed to enhance the accessibility of healthcare for the elderly. The aim of the study is to explore the effectiveness of the new care service, based on Andersen model, regarding health service utilization, health status and service satisfaction. Methods: The effectiveness of medical-nursing combined care will be measured in a cross sectional study in nine nursing homes in Jianghan District, Wuhan, China, with 1067 old residents expected to participate. The questionnaire containing items of demographics, health service use, service satisfaction and instrument of SF-36 V2 is developed based on the conceptual framework of Andersen behaviour model of health service utilization. Descriptive analysis, variance analysis, multiple factors analysis, and correlation analysis will be performed to compare the sociological characteristics, health service use, health status and service satisfaction of the elderly living in different modes of nursing homes, to explore the influence factors of care effectiveness, as well as to study the relationship between health behaviour and health outcomes. Conclusion: The study design of analysing the effects of medical-nursing combined care and performing the horizontal comparison among the nursing homes under the framework of Andersen model is blazing new trails. Recruitment and design of questionnaire are important issues. Successful data collection and quality control are also necessary. Taking these into account, this study is estimated to provide evidence for the effectiveness of medical-nursing combined care service in China. PMID- 27398941 TI - Use of Improved Orbitals for CCSD(T) Calculations for Predicting Heats of Formation of Group IV and Group VI Metal Oxide Monomers and Dimers and UCl6. AB - The prediction of the heats of formation of group IV and group VI metal oxide monomers and dimers with the coupled cluster CCSD(T) method has been improved by using Kohn-Sham density functional theory (DFT) and Brueckner orbitals for the initial wave function. The valence and core-valence contributions to the total atomization energies for the CrO3 monomer and dimer are predicted to be significantly larger than when using the Hartree-Fock (HF) orbitals. The predicted heat of formation of CrO3 with CCSD(T)/PW91 is consistent with previous calculations including high-order corrections beyond CCSD(T) and agrees well with the experiment. The improved heats of formation with the DFT and Brueckner orbitals are due to these orbitals being closer to the actual orbitals. Pure DFT functionals perform slightly better than the hybrid B3LYP functional due to the presence of exact exchange in the hybrid functional. Comparable heats of formation for TiO2 and the second- and the third-row group IV and group VI metal oxides are predicted well using either the DFT PW91 orbitals, Brueckner orbitals, or HF orbitals. The normalized clustering energies for the dimers are consistent with our previous work except for a larger value predicted for Cr2O6. The prediction of the reaction energy for UF6 + 3Cl2 -> UCl6 + 3F2 was significantly improved with the use of DFT or Brueckner orbitals as compared to HF orbitals. PMID- 27398938 TI - Detecting and discriminating novel objects: The impact of perirhinal cortex disconnection on hippocampal activity patterns. AB - Perirhinal cortex provides object-based information and novelty/familiarity information for the hippocampus. The necessity of these inputs was tested by comparing hippocampal c-fos expression in rats with or without perirhinal lesions. These rats either discriminated novel from familiar objects (Novel Familiar) or explored pairs of novel objects (Novel-Novel). Despite impairing Novel-Familiar discriminations, the perirhinal lesions did not affect novelty detection, as measured by overall object exploration levels (Novel-Novel condition). The perirhinal lesions also largely spared a characteristic network of linked c-fos expression associated with novel stimuli (entorhinal cortex->CA3 >distal CA1->proximal subiculum). The findings show: I) that perirhinal lesions preserve behavioral sensitivity to novelty, whilst still impairing the spontaneous ability to discriminate novel from familiar objects, II) that the distinctive patterns of hippocampal c-fos activity promoted by novel stimuli do not require perirhinal inputs, III) that entorhinal Fos counts (layers II and III) increase for novelty discriminations, IV) that hippocampal c-fos networks reflect proximal-distal connectivity differences, and V) that discriminating novelty creates different pathway interactions from merely detecting novelty, pointing to top-down effects that help guide object selection. (c) 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID- 27398943 TI - Delivering compassionate care in intensive care units: nurses' perceptions of enablers and barriers. AB - BACKGROUND: Compassion is core to nursing practice. Nurses' expression of compassion is a complex interaction informed by the nurse, the patient and the practice environment. AIM: The aim of this study was to identify personal, professional and organizational factors, intensive care nurses, in a major metropolitan facility in Australia, identified as enabling or disabling them to be compassionate. DESIGN: Intensive care nurses (n = 171) reflected on their experiences during 'compassion cafes' conducted in 2015. METHOD: Qualitative, reflexive methods were used to explore ICU nurses' perceptions of enablers and barriers. Nurses documented their perceptions, which were thematically analysed. Meanings were subsequently verified with participants. RESULTS: The findings identified multiple factors both inside and outside the workplace that constrained or enabled nurses' ability to be compassionate. Two main factors inside the workplace were culture of the team, in particular, support from colleagues and congruency in work practices and decision-making, and connections with patients and families. Outside the workplace, nurses were influenced by their values about care and lifestyle factors such as family demands. CONCLUSIONS: Nurses capacity to be compassionate is a complex interplay between nursing knowledge and expectations, organizational structures and lifestyle factors. IMPLICATIONS: The responsibility for 'compassionate' care is a shared one. Nurses need to be cognizant of factors that are enabling or inhibiting their ability to be compassionate. Healthcare leaders have a responsibility to provide structural support (staffing, education and space) that assist nurses to deliver compassionate care and where appropriate cater for nurses needs so that they are better able to be compassionate. PMID- 27398945 TI - Identification of monogenic gene mutations in Japanese subjects diagnosed with type 1B diabetes between >5 and 15.1 years of age. AB - BACKGROUND: Monogenic mutations, such as those in the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) and insulin (INS) genes, are identified in young patients with type 1B diabetes (non-autoimmune-mediated). We recently reported the results of a test for monogenic forms of diabetes in Japanese children who were diagnosed with type 1B diabetes at <5 years of age. In this study, we tested for monogenic forms of diabetes in Japanese children aged >5 to <=15.1 years at the diagnosis of type 1B diabetes. METHODS: Thirty-two Japanese children (eight males, 24 females) with type 1 diabetes negative for glutamate decarboxylase (GAD) 65 and/or IA-2A autoantibodies and who were aged >5 to 15.1 years at diagnosis were recruited from 16 independent hospitals participating in the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT). We performed mutational analyses of genes with a high frequency of mutation [INS, KCNJ11, hepatocyte nuclear factor 1 alpha (HNF1alpha) and hepatocyte nuclear factor 4 alpha (HNF4alpha)]. RESULTS: We identified one missense mutation (G32S) in the INS gene and two mutations (R131Q and R203S) in the HNF1alpha gene that could be associated with diabetes. No missense change was found in the KCNJ11 gene. CONCLUSIONS: Our results suggest that although mutations in the INS gene can be detected in Japanese patients aged >5 years at diagnosis, the frequency of mutations decrease in older age groups. Conversely, the frequency of the mutation in the HNF1alpha gene increased in patients diagnosed at age 5 or older. Clinicians should consider the possibility of maturity onset diabetes of the young (MODY) in children diagnosed with type 1B diabetes. PMID- 27398946 TI - Brien Holden: a remarkable life in optometry. PMID- 27398947 TI - The lack of public health teaching for medical students reinforces false stereotypes. PMID- 27398948 TI - Serial procalcitonin levels for predicting prognosis in community-acquired pneumonia. AB - BACKGROUND AND OBJECTIVE: This study aimed to investigate the usefulness of addition of serial measurements of procalcitonin (PCT) to C-reactive protein (CRP) values and pneumonia severity scores, such as CURB-65 (confusion, urea > 7 mmol/L, respiratory rate >= 30 breaths/min, low blood pressure (systolic < 90 mm Hg or diastolic <= 60 mm Hg) and age >= 65 years) and the Pneumonia Severity Index, and attempted to create and evaluate a new scoring system for predicting mortality risk using the biomarkers and pneumonia severity scores. METHODS: A total of 365 hospitalized community-acquired pneumonia (CAP) patients in an observational cohort study in which PCT was measured serially from admission to 2 3 days after admission between December 2010 and December 2014 were reviewed retrospectively. PCT and CRP were measured on admission (PCT D1 and CRP D1) and within 48-72 h after admission (PCT D3 and CRP D3). RESULTS: Twenty-one patients died (5.8%), and 52 patients (14.2%) did not respond to initial therapy. On multivariate analysis, CRP D1 >= 100 mg/L (P = 0.002), CURB-65 >= 3 (P < 0.001) and PCT D3/D1 >= 1 (P < 0.001) were significant predictors of 30-day mortality. Peak CRP (P = 0.02) and PCT D3/D1 >= 1 (P = 0.03) were significant predictors of initial treatment failure. Using the new scoring system that defines CRP D1 >= 100 mg/L as 2 points, CURB-65 >= 3 as 1 point and PCT D3/D1 >= 1 as 1 point, in CAP patients with both CRP D1 >= 100 mg/L and CURB-65 >= 3 on admission, the 30 day mortality rate was 21.8%, and with PCT D3/D1 >= 1, it increased to 50.0%. CONCLUSION: It is useful to add serial measurements of PCT to CRP measurement and assessment of CURB-65 on admission of CAP patients to predict prognosis and initial treatment failure. PMID- 27398949 TI - Surgical Technique and Initial Clinical Experience with a Novel Extracapsular Articulating Implant for Treatment of the Canine Cruciate Ligament Deficient Stifle Joint. AB - OBJECTIVE: To describe the surgical technique, clinical efficacy, and complications using the Simitri Stable in Stride((r)) extracapsular articulating implant (EAI) to treat naturally occurring stifle instability due to cranial cruciate ligament (CrCL) insufficiency. STUDY DESIGN: Prospective case series. ANIMALS: Client-owned dogs with CrCL-deficient stifles (n=60 dogs; 66 stifles). METHODS: An EAI was applied to the medial aspect of the distal femur and proximal tibia after stifle exploration and treatment of joint pathology. Outcome measures included lameness score, time to weight bearing, and bilateral assessment of stifle stability, stifle range of motion (ROM), and thigh circumference (TC). Outcome measures were determined preoperatively and at intervals from 4.5 to 16.0 months (median 8.9 months) postoperatively. Data were excluded from bilaterally affected dogs <6 months after CrCL surgery on the contralateral limb, and from dogs with contralateral limb lameness. RESULTS: Within 24 hours of EAI surgery, dogs were weight bearing on 64 of 66 limbs at the walk. Incidence of major complications requiring surgical revision was 15.3% and minor complications was 10.2%. Postoperatively, there were significant improvements in lameness scores and ROM in 34 EAI-treated limbs meeting inclusion criteria, and the mean ROM returned to within normal limits. TC did not change in the operated limb, but decreased significantly in the control limb. CONCLUSION: The EAI effectively stabilized the CrCL-deficient stifle, and significantly improved lameness scores and stifle ROM. Decreased TC in control limbs may have been due to early return to mobility and weight bearing on the EAI-treated limb. PMID- 27398954 TI - Editor's notes. PMID- 27398952 TI - A Single Institution Review of Initial Application of a 5-mm Stapler. AB - BACKGROUND: Operating in small spaces presents physical constraints that can be even more challenging in minimally invasive operations. Recently, a 5-mm stapler was approved for use in general surgery and pediatric surgery. Here, we present our initial experience using the 5-mm stapler in pediatric general surgery. MATERIALS AND METHODS: A retrospective chart review was conducted to identify cases using the 5-mm stapler at our institution. Demographic data included age (in months) and weight (in kilograms). Operative data included indication for use, number of loads used, complications related to 5-mm stapler use, and interventions to address complications. A second review focused on patients undergoing the same operations, but using a 10-mm stapler. RESULTS: A total of 60 staple loads were deployed in 32 procedures. There were four adverse outcomes, all recognized intraoperatively. One bleed resulted from application on irradiated tissue and another bleed from application to a small noninflamed mesoappendix. A bronchial staple line leak resulted from improper stapler loading, and a bowel anastomosis leak was oversewn with a single stitch. When compared with 32 matched cases using a 10-mm stapler, there was no difference in age (5-mm = 39.11 months, 10-mm = 50.21 months, P = .49) or weight (5-mm = 16.34 kg, 10-mm = 19.93 kg, P = .51). A total of 60 staple applications were used, with one bleed noted. There was no significant difference in overall complication rate (5-mm rate = 4/60, 10-mm rate = 1/60; P = .36). CONCLUSION: Our initial experience suggests that although there were more complications with the 5-mm stapler, there is no statistically significant difference in complication rates when compared with the 10-mm stapler. Furthermore, the 5-mm stapler complications can be corrected with device training and proper patient selection. In appropriately selected pediatric surgery cases with size limitations, the 5-mm stapler can be used to minimize the invasiveness of the operation. PMID- 27398953 TI - Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease. AB - OBJECTIVE: Deposition of amyloid beta (Abeta)-containing plaques as evidenced by amyloid imaging and cerebrospinal fluid (CSF) Abeta1-42 (Abeta42) is an early indicator of preclinical Alzheimer disease (AD). To better understand their relationship during the earliest preclinical stages, we investigated baseline CSF markers in cognitively normal individuals at different stages of amyloid deposition defined by longitudinal amyloid imaging with Pittsburgh compound B (PIB): (1) PIB-negative at baseline and follow-up (PIB(-) ; normal), (2) PIB negative at baseline but PIB-positive at follow-up (PIB converters; early preclinical AD), and (3) PIB-positive at baseline and follow-up (PIB(+) ; preclinical AD). METHODS: Cognitively normal individuals (n = 164) who had undergone baseline PIB scan and CSF collection within 1 year of each other and at least 1 additional PIB follow-up were included. Amyloid status was defined dichotomously using an a priori mean cortical cutoff. RESULTS: PIB converters (n = 20) at baseline exhibited significantly lower CSF Abeta42 compared to those who remained PIB-negative (n = 123), but higher compared to the PIB(+) group (n = 21). A robust negative correlation (r = -0.879, p = 0.0001) between CSF Abeta42 and absolute (but subthreshold) PIB binding was observed during this early preclinical stage. The negative correlation was not as strong once individuals were PIB-positive (r = -0.456, p = 0.038), and there was no correlation in the stable PIB(-) group (p = 0.905) or in the group (n = 10) with early symptomatic AD (p = 0.537). INTERPRETATION: CSF Abeta42 levels are tightly coupled with cortical amyloid load in the earliest stages of preclinical AD, and begin to decrease dramatically prior to the point when an abnormal threshold of cortical accumulation is detected with amyloid imaging. Ann Neurol 2016;80:379-387. PMID- 27398956 TI - Sportspages. PMID- 27398955 TI - Letters. PMID- 27398957 TI - Coming of Age in Red Bank. PMID- 27398958 TI - O Hardy Pioneers! PMID- 27398959 TI - Prevention and Treatment of Tennis Elbow. PMID- 27398960 TI - Prevention and Treatment of Tennis Elbow. PMID- 27398961 TI - Cme credit quiz. PMID- 27398962 TI - Do Risks of Exercise Justify Costly Caution? PMID- 27398963 TI - Stress Testing Indicated in a Variety of Complaints. PMID- 27398964 TI - Student of Motion Is a Study in Motion. PMID- 27398965 TI - Have Squeeze Bottle, Will Run, Says Diabetic. PMID- 27398966 TI - A need to know. PMID- 27398968 TI - Certifying Exercise Directors. PMID- 27398967 TI - Where are they now? PMID- 27398969 TI - J. P. R. Williams: Is Pain His Middle Name? PMID- 27398970 TI - Prevention of Tennis Elbow Through Conditioning. PMID- 27398972 TI - Parental ADHD and Depression: Time-Varying Prediction of Offspring Externalizing Psychopathology. AB - Parental attention deficit/hyperactivity disorder (ADHD) and depression are risk factors for negative child outcomes, but given their frequent co-occurrence and variability over time, developmentally sensitive studies are needed. To characterize change in parental ADHD and depression as predictors of change in child ADHD and oppositional defiant disorder (ODD), 230 five- to ten-year-old children with (n = 110) and without (n = 120) ADHD were followed prospectively for 2 years with 90% retention. At baseline and again 2 years later (i.e., Wave 2), parents self-reported their ADHD and depression; parents and teachers also separately rated child ADHD and ODD, as well as broader attention and externalizing problems. Controlling for child sex, race-ethnicity, age, and parental depression, generalized estimating equations revealed that 2-year decreases in parental ADHD significantly predicted reduced child ADHD symptoms, but only among non-ADHD youth. Alternatively, increasing parental depression positively predicted change in teacher-rated ODD symptoms. These findings provide quasi-experimental evidence that parental ADHD and depression may be time-varying risk factors with respect to key dimensions of child externalizing behavior problems. We consider the potential dynamic and reciprocal interrelations among parental ADHD and depression with developmental change in offspring ADHD and ODD. We also discuss implications of parent psychopathology in the development of interventions to reduce the burden of youth ADHD and associated externalizing behavior. PMID- 27398973 TI - A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50. AB - Polyester microspheres are extensively studied for controlled release drug delivery devices, and many models have been developed to describe drug release from the bulk polymer. However, the interaction between drugs and polymers is ignored in most of the existing mathematical models. This paper presents a mechanistic model which captures the interplay between acidic drugs and bioresorbable polyesters. The model considers the autocatalytic effect on polymer degradation arising from carboxylic acid end groups of oligomers and drug molecules. Hence, the enhancing effect of acidic drug on the rate of degradation was fully considered. On the other hand the drug release from polyester microspheres is controlled by drug diffusion from polymer matrix. The drug diffusion coefficient depends strongly on the level of degradation of the polymer. This effect is also included in the model. It is shown that the model can effectively predict experimental data in the literature for both polymer degradation and drug release. Furthermore, the model is used to design different systems of microspheres which release drugs with either a zero order profile or burst followed by zero order release profile. PMID- 27398975 TI - Occupational health and safety in hospitals accreditation system: the case of Lebanon. AB - INTRODUCTION: Hospital accreditation can be an incentive to improve occupational health and safety (OHS) performance. OBJECTIVE: This study assesses the relationship between status of accreditation among private Lebanese hospitals and compliance with OHS accreditation standards. METHODS: A survey was administered to 68 private Lebanese hospitals to assess accreditation status and specific indicators related to each of the 9 OHS codes in the Lebanese accreditation manual. Chi-square, Fisher's exact test, and independent sample t-tests compared the OHS standards between accredited and non-accredited hospitals. RESULTS: Fifty six percent of participating private hospitals were accredited. Accredited hospitals reported statistically better OHS performance than non-accredited hospitals based on the standards outlined in the accreditation manual. However, there was inconsistent performance on numerous OHS indicators among participating hospitals. CONCLUSION: The gaps in OHS performance suggest the need for strengthened OHS guidelines in the national accreditation process to safeguard workers' health. Strategies to fortify OHS performance include tying service reimbursement to OHS compliance and linking OHS standards with national labor legislation. PMID- 27398974 TI - Hyaluronan Depolymerization by Megakaryocyte Hyaluronidase-2 Is Required for Thrombopoiesis. AB - Hyaluronan is the predominant glycosaminoglycan component of the extracellular matrix with an emerging role in hematopoiesis. Modulation of hyaluronan polymer size is responsible for its control over cellular functions, and the balance of hyaluronan synthesis and degradation determines its molecular size. Although two active somatic hyaluronidases are expressed in mammals, only deficiency in hyaluronidase-2 (Hyal-2) results in thrombocytopenia of unknown mechanism. Our results reveal that Hyal-2 knockout mice accumulate hyaluronan within their bone marrow and within megakaryocytes, the cells responsible for platelet generation. Proplatelet formation by Hyal-2 knockout megakaryocytes was disrupted because of abnormal formation of the demarcation membrane system, which was dilated and poorly developed. Importantly, peptide-mediated delivery of exogenous hyaluronidase rescued deficient proplatelet formation in murine and human megakaryocytes lacking Hyal-2. Together, our data uncover a previously unsuspected mechanism of how hyaluronan and Hyal-2 control platelet generation. PMID- 27398976 TI - Contrived motivating operations alter delay-discounting values of disordered gamblers. AB - The present study required 9 disordered gamblers to make hypothetical selections between smaller and larger amounts of money at varying delays. Participants were also required to respond to the task given the contrived hypothetical conditions of earning twice or half as much as they did at their current jobs. The results demonstrated how participants' delay discounting was altered via contrived motivating operations, strengthening the argument that discounting may be a state variable. PMID- 27398977 TI - Kinetics of cytochrome c oxidase from R. sphaeroides initiated by direct electron transfer followed by tr-SEIRAS. AB - Time-resolved surface-enhanced IR-absorption spectroscopy (tr-SEIRAS) has been performed on cytochrome c oxidase from Rhodobacter sphaeroides. The enzyme was converted electrochemically into the fully reduced state. Thereafter, in the presence of oxygen, the potential was switched to open circuit potential (OCP). Under these conditions, the enzyme is free to undergo enzymatic oxidation in the absence of an external electric field. Tr-SEIRAS was performed using the step scan technique, triggered by periodic potential pulses switching between - 800mV and OCP. Single bands were resolved in a broad band in the amide I region using phase sensitive detection. Amplitudes of these bands were analyzed as a function of time. Time constants in the ms time scale were considered in terms of conformational changes of the protein secondary structures associated with the enzymatic turnover of the protein. PMID- 27398978 TI - Cyclic voltammetry of apple fruits: Memristors in vivo. AB - A memristor is a resistor with memory that exhibits a pinched hysteretic relationship in cyclic voltammetry. Recently, we have found memristors in the electrical circuitry of plants and seeds. There are no publications in literature about the possible existence of memristors and electrical differentiators in fruits. Here we found that the electrostimulation of Golden Delicious or Arkansas Black apple fruits by bipolar periodic waves induces hysteresis loops with pinched points in cyclic voltammograms at low frequencies between 0.1MHz and 1MHz. At high frequencies of 1kHz, the pinched hysteresis loop transforms to a non-pinched hysteresis loop instead of a single line I=V/R for ideal memristors because the amplitude of electrical current depends on capacitance of a fruit's tissue and electrodes, frequency and direction of scanning. Electrostimulation of electrical circuits in apple fruits by periodic voltage waves also induces electrotonic potential propagation due to cell-to-cell electrical coupling with electrical differentiators. A differentiator is an electrical circuit in which the output of the circuit is approximately directly proportional to the rate of change of the input. The information gained from electrostimulation can be used to elucidate and to observe electrochemical and electrophysiological properties of electrical circuits in fruits. PMID- 27398979 TI - Proteomics approaches in cervical cancer: focus on the discovery of biomarkers for diagnosis and drug treatment monitoring. AB - INTRODUCTION: The HPV virus accounts for the majority of cervical cancer cases. Although a diagnostic tool (Pap Test) is widely available, cervical cancer incidence still remains high worldwide, and especially in developing countries, attributed to a large extent to suboptimal sensitivities of the Pap test and unavailability of the test in developing countries. AREAS COVERED: Proteomics approaches have been used in order to understand the HPV virus correlation to cervical cancer pathology, as well as to discover putative biomarkers for early cervical cancer diagnosis and drug mode of action. Expert commentary: The present review summarizes the latest in vitro and in vivo proteomic studies for the discovery of putative cervical cancer biomarkers and the evaluation of available drugs and treatments. PMID- 27398980 TI - Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease. AB - BACKGROUND: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. METHODS: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. RESULTS: Variations in systolic BP (-11.76 +/- 17.1 mm Hg), diastolic BP (-4.92 +/- 10.3 mm Hg) and pulse pressure (-6.84 +/- 12.6 mm Hg) were significant after 1 year (n = 191; x03C1; < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (x03C1; < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (x03C1; = 0.069) or diastolic BP (x03C1; = 0.079), and in basic independence only regarding risen diastolic BP (x03C1; = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. CONCLUSIONS: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD. PMID- 27398981 TI - Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function. AB - Oropharyngeal dysphagia (OD) is very prevalent among poststroke patients, causing severe complications but lacking specific neurorehabilitation treatment. This review covers advances in the pathophysiology, diagnosis, and physiologically based neurorehabilitation strategies for poststroke OD. The pathophysiology of oropharyngeal biomechanics can be assessed by videofluoroscopy, as delayed laryngeal vestibule closure is closely associated with aspiration. Stroke may affect afferent or efferent neuronal circuits participating in deglutition. The integrity of oropharyngeal-cortical afferent pathways can be assessed by electroencephalography through sensory-evoked potentials by pharyngeal electrical stimulation, while corticopharyngeal efferent pathways can be characterized by electromyography through motor-evoked potentials by transcranial magnetic stimulation. Dysfunction in both cortico-mediated evoked responses is associated with delayed swallow response and aspiration. Studies have reported hemispherical asymmetry on motor control of swallowing and the relevance of impaired oropharyngeal sensitivity on aspiration. Advances in treatment include improvements in compensatory strategies but are mainly focused on (1) peripheral stimulation strategies and (2) central, noninvasive stimulation strategies with evidence of their clinical benefits. Characterization of poststroke OD is evolving from the assessment of impaired biomechanics to the sensorimotor integration processes involved in deglutition. Treatment is also changing from compensatory strategies to promoting brain plasticity, both to recover swallow function and to improve brain-related swallowing dysfunction. PMID- 27398982 TI - Concentration-Response Relationship of Hearing Impairment Caused by Quinine and Salicylate: Pharmacological Similarities but Different Molecular Mechanisms. AB - This review has the purpose to summarize concentration-effect studies made with quinine and to compare the effects on hearing between quinine and salicylate. Quinine and salicylate have roles in experimental hearing research and may induce pronounced and reversible hearing impairment when administered in sizeable doses. The quinine-induced increase in hearing threshold and its recovery can be analysed according to 'the psychophysical power function'. The power function is a special case of the Hill equation when the stimulus (e.g. a drug concentration) is exceedingly small compared with the concentration that would elicit a half maximum response. Quinine and salicylate induce sensorineural hearing impairment and tinnitus when given in higher dose ranges in man. The drugs influence the presence, magnitude, and quality of audiological responses, such as spontaneous and evoked otoacoustic emissions. Quinine reversibly reduces frequency selectivity and hearing sensitivity, whereas the self-attained most comfortable speech level and the acoustic stapedius reflex are not affected, that is the dynamic range of hearing is reversibly reduced. This observation supports the view that quinine acts on the outer hair cell of the cochlea. Both drugs share a protective effect against the permanent hearing damages caused by gentamicin. This action is interpreted as a request for functioning mechanoelectric transducer (MET) channels to elicit the ill effect of aminoglycosides. Both drugs may interfere with the cochlear amplifier through blocking MET channels and the motor protein prestin. This review finds considerable overlap between type and extent of pharmacological actions of quinine and salicylate, supposedly caused by partly shared mechanisms of action but performed with different molecular mechanisms. PMID- 27398983 TI - Prevalence and mortality of abdominal compartment syndrome in severely injured patients: A systematic review. AB - BACKGROUND: Abdominal compartment syndrome (ACS) in severely injured patients is associated with high morbidity and mortality. Many efforts have been made to improve outcome of patients with ACS. A treatment algorithm for ACS patients was introduced on January 1, 2005 by the World Society of the Abdominal Compartment Syndrome. The aim of this study was to determine the prevalence and mortality rate of ACS among severely injured patients before and after January 1, 2005 using a systematic literature review. METHOD: Databases of Embase, Medline (OvidSP), Web of Science, CINAHL, CENTRAL, PubMed publisher, and Google Scholar were searched for terms related to severely injured patients and ACS. Original studies reporting ACS in trauma patients were considered eligible. Data on study design, population, definitions, prevalence, and mortality rates were extracted. Pooled prevalence and mortality of ACS among severely injured patients were calculated for both time periods using inversed variance weighting assuming a random effects model. Tests for heterogeneity were applied. RESULTS: A total of 80 publications were included. Prevalence of studies that finished enrolling patients before January 1, 2005 ranged from 0.5% to 36.4% and 0.0% to 28.0% in studies after that date. For severely injured patients admitted to the ICU, this range was 0.5% to 1.3% before 2005 and 0% in one publication in the second time period. For patients with visceral injuries, ACS prevalence ranged 1.0% to 20.0%; one study in the second time period reported 11.1%. The prevalence among severely injured patients who underwent trauma laparotomy ranged from 0.9% to 36.4% in the first time period. Two studies after January 1, 2005 reported ACS prevalence of 2.3% and 13.2%, respectively. The mortality rate in both time periods ranged between 0.0% and 100.0%. CONCLUSION: The overall prevalence of ACS ranged from 0.0% to 36.4%. Future studies are needed to measure the effect of improved trauma care and effectiveness of the World Society of the Abdominal Compartment Syndrome Consensus Statements. LEVEL OF EVIDENCE: Systematic review/meta-analysis, level III. PMID- 27398984 TI - The long-term burden of severe sepsis and septic shock: Sepsis recidivism and organ dysfunction. AB - BACKGROUND: Severe sepsis and septic shock mortality has improved; however, rates of persistent (28-90 days) and long-term (>90 day) organ dysfunction in sepsis survivors are unknown. METHODS: Secondary analysis of a prospective cohort of adult emergency department patients with severe sepsis. RESULTS: Of 110 sepsis admissions, we obtained follow-up on 51 of 78 survivors of whom 41% (21 of 51) had persistent organ dysfunction: pulmonary, 18% (9 of 51); renal, 22% (11 of 51); coagulopathy, 10% (5 of 51); cardiovascular, 6% (3 of 51); hepatic, 2% (1 of 51); and neurologic, 3% (3 of 51). We obtained follow-up on 40 of 73 survivors at more than 90 days of whom 38% (15 of 40) had long-term organ dysfunction: pulmonary, 13% (5 of 40); renal, 18% (7 of 40); coagulopathy, 3% (1 of 40); cardiovascular, 5% (2 of 40); hepatic, 0%; and neurologic, 5% (2 of 40). Readmission rate within 90 days was 32% (25 of 78), and recurrent sepsis was the cause of readmission in 52% (13 of 25). Baseline SOFA scores from the index sepsis admission were compared using Wilcoxon rank-sum test and were significantly different in participants with organ dysfunction versus those without organ dysfunction at less than 90 days (z, -2.51; p = 0.01). CONCLUSION: Readmission with recurrent sepsis and organ dysfunction occurs frequently in sepsis survivors. Baseline SOFA score may be predictive of sepsis recidivism and persistent or recurrent organ dysfunction. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level IV. PMID- 27398985 TI - Characterization of erythropoietin and hepcidin in the regulation of persistent injury-associated anemia. AB - BACKGROUND: The cause of persistent injury-associated anemia is multifactorial and includes acute blood loss, an altered erythropoietin (EPO) response, dysregulation of iron homeostasis, and impaired erythropoiesis in the setting of chronic inflammation/stress. Hepcidin plays a key role in iron homeostasis and is regulated by anemia and inflammation. Erythropoietin is a main regulator of erythropoiesis induced by hypoxia. A unique rodent model of combined lung injury (LC)/hemorrhagic shock (HS) (LCHS)/chronic restraint stress (CS) was used to produce persistent injury-associated anemia to further investigate the roles of EPO, hepcidin, iron, ferritin, and the expression of EPO receptors (EPOr). METHODS: Male Sprague-Dawley rats were randomly assigned into one of the four groups of rodent models: naive, CS alone, combined LCHS, or LCHS/CS. Plasma was used to evaluate levels of EPO, hepcidin, iron, and ferritin. RNA was isolated from bone marrow and lung tissue to evaluate expression of EPOr. Comparisons between models were performed by t tests followed by one-way analysis of variance. RESULTS: After 7 days, only LCHS/CS was associated with persistent anemia despite significant elevation of plasma EPO. Combined LCHS and LCHS/CS led to a persistent decrease in EPOr expression in bone marrow on Day 7. The LCHS/CS significantly decreased plasma hepcidin levels by 75% on Day 1 and 84% on Day 7 compared to LCHS alone. Hepcidin plasma levels are inversely proportional to EPO plasma levels (Pearson R = -0.362, p < 0.05). CONCLUSION: Tissue injury, hemorrhagic shock, and stress stimulate and maintain high levels of plasma EPO while hepcidin levels are decreased. In addition, bone marrow EPOr and plasma iron availability are significantly reduced following LCHS/CS. The combined deficit of reduced iron availability and reduced bone marrow EPOr expression may play a key role in the ineffective EPO response associated with persistent injury associated anemia. PMID- 27398986 TI - Spotlight on environmental omics and toxicology: a long way in a short time. AB - The applications for high throughput omics technologies in environmental science have increased dramatically in recent years. Transcriptomics, proteomics, and metabolomics have been used to study how chemicals in our environment affect both aquatic and terrestrial organisms, and the characterization of molecular initiating events is a significant goal in toxicology to better predict adverse responses to toxicants. This special journal edition demonstrates the scope of the science that leverages omics-based methods in both laboratory and wild populations within the context of environmental toxicology, ranging from fish to mammals. It is important to recognize that the environment comprises one axis of the One Health concept - the idea that human health is unequivocally intertwined to our environment and to the organisms that inhabit that environment. We have much to learn from a comparative approach, and studies that integrate the transcriptome, proteome, and the metabolome are expected to offer the most detailed mechanism-based adverse outcome pathways that are applicable for use in both environmental monitoring and risk assessment. PMID- 27398987 TI - The regenerative effects of electromagnetic field on spinal cord injury. AB - Traumatic spinal cord injury (SCI) is typically the result of direct mechanical impact to the spine, leading to fracture and/or dislocation of the vertebrae along with damage to the surrounding soft tissues. Injury to the spinal cord results in disruption of axonal transmission of signals. This primary trauma causes secondary injuries that produce immunological responses such as neuroinflammation, which perpetuates neurodegeneration and cytotoxicity within the injured spinal cord. To date there is no FDA-approved pharmacological agent to prevent the development of secondary SCI and induce regenerative processes aimed at healing the spinal cord and restoring neurological function. An alternative method to electrically activate spinal circuits is the application of a noninvasive electromagnetic field (EMF) over intact vertebrae. The EMF method of modulating molecular signaling of inflammatory cells emitted in the extra-low frequency range of <100 Hz, and field strengths of <5 mT, has been reported to decrease inflammatory markers in macrophages, and increase endogenous mesenchymal stem cell (MSC) proliferation and differentiation rates. EMF has been reported to promote osteogenesis by improving the effects of osteogenic media, and increasing the proliferation of osteoblasts, while inhibiting osteoclast formation and increasing bone matrix in vitro. EMF has also been shown to increase chondrogenic markers and collagen and induce neural differentiation, while increasing cell viability by over 50%. As advances are made in stem cell technologies, stabilizing the cell line after differentiation is crucial to SCI repair. Once cell-seeded scaffolds are implanted, EMF may be applied outside the wound for potential continued adjunct treatment during recovery. PMID- 27398988 TI - Interfacial Stabilization of Fiber-Laden Foams with Carboxymethylated Lignin toward Strong Nonwoven Networks. AB - Wet foams were produced via agitation and compressed air bubbling of aqueous solutions of carboxymethylated lignin (CML). Bubble size and distribution were assessed in situ via optical microscopy. Foamability, bubble collapse rate, and foam stability (half-life time) were analyzed as a function of CML concentration, temperature, pH, and air content. Dynamic changes of the CML liquid foam were monitored by light transmission and backscattering. Cellulosic fibers of different aspect ratios (long pine fibers and short birch fibers) were suspended under agitation by the liquid foams (0.6% CML in the aqueous phase) with an air (bubble) content as high as 75% in volume. Remarkably, the half-life time of fiber-laden CML foams was 10-fold higher than that of the corresponding fiber free liquid foam. Such lignin-based foams were demonstrated, after dewatering, as a precursor for the synthesis of nonwoven, layered structures. The resulting fiber networks (paper), obtained here for the first time with lignin-based foams, were characterized for pore size distribution, lignin retention, morphology, and physical-mechanical properties (network formation quality, density, air permeability, surface roughness, and tensile and internal bond strengths). The results were compared against structures obtained from foams stabilized with an anionic surfactant (SDS) as well as those from foam-free, water-based web-laying. Remarkably, compared to SDS, the foam-formed materials produced with CML displayed better bonding and tensile strengths. Overall, CML-based foams were found to be suitable carriers of cellulosic fibers and have opened the possibility for integrating fully biobased systems in foam-forming. This is an emerging option to increase the effective solids content in the system without compromising the quality of formed nonwoven materials while achieving reductions in water and energy consumption. PMID- 27398989 TI - Marijuana use and viral suppression in persons receiving medical care for HIV infection. AB - BACKGROUND: Marijuana use is common among persons living with HIV (PLWH), but studies on its effect on HIV clinical outcomes are limited. OBJECTIVES: We determined the association between marijuana use and HIV viral suppression among PLWH. METHODS: Data came from five repeated cross-sections (2009-2013) of the Florida Medical Monitoring Project, a population-based sample of PLWH in Florida. Data were obtained via interview and medical record abstraction (MRA). Weighted logistic regression models were used to determine the association between marijuana use (past 12 months) and durable viral suppression (HIV-1 RNA value of <= 200 copies/milliliter in all measurements within the past 12 months). RESULTS: Of the 1,902 PLWH receiving antiretroviral therapy, completed an interview, and had a linked MRA, 20% reported marijuana use (13% less than daily and 7% daily use) and 73% achieved durable viral suppression. In multivariable analysis, marijuana use was not significantly associated with durable viral suppression in daily [Adjusted Odds Ratio (AOR): 0.87, 95% confidence interval (CI): 0.58, 1.33] or in less than daily [AOR: 0.83, 95% CI: 0.51, 1.37] users as compared to non users when adjusting for sociodemographic factors, time since HIV diagnosis, depressive symptoms, alcohol, cigarette and other substance use. CONCLUSION: In this sample of PLWH receiving medical care in Florida, there was no statistically significant association between marijuana use and viral suppression. However, as the limits of the confidence intervals include effects that may be considered to be clinically important, there is a need for additional evidence from other samples and settings that include more marijuana users. PMID- 27398990 TI - Improving Communication About Serious Illness in Primary Care: A Review. AB - IMPORTANCE: The Institute of Medicine recently called for systematic improvements in clinician-led conversations about goals, values, and care preferences for patients with serious and life-threatening illnesses. Studies suggest that these conversations are associated with improved outcomes for patients and their families, enhanced clinician satisfaction, and lower health care costs; however, the role of primary care clinicians in driving conversations about goals and priorities in serious illness is not well defined. OBJECTIVE: To present a review of a structured search of the evidence base about communication in serious illness in primary care. EVIDENCE REVIEW: MEDLINE was searched, via PubMed, on January 19, 2016, finding 911 articles; 126 articles were reviewed and selected titles were added from bibliography searches. FINDINGS: Review of the literature informed 2 major topic areas: the role of primary care in communication about serious illness and clinician barriers and system failures that interfere with effective communication. Literature regarding the role that primary care plays in communication focused primarily on the ambiguity about whether primary care clinicians or specialists are responsible for initiating conversations, the benefits of primary care clinicians and specialists conducting conversations, and the quantity and quality of discussions. Timely and effective communication about serious illness in primary care is hampered by key clinician barriers, which include deficits in knowledge, skills, and attitudes; discomfort with prognostication; and lack of clarity about the appropriate timing and initiation of conversations. Finally, system failures in coordination, documentation, feedback, and quality improvement contribute to lack of conversations. CONCLUSIONS AND RELEVANCE: Clinician and system barriers will challenge primary care clinicians and institutions to meet the needs of patients with serious illness. Ensuring that conversations about goals and values occur at the appropriate time for seriously ill patients will require improved training, validation, and dissemination of patient selection tools, systems for conducting and revisiting conversations, accessible documentation, and incentives for measurement, feedback, and continuous improvement. PMID- 27398991 TI - Unloading Shoes for Self-management of Knee Osteoarthritis: A Randomized Trial. AB - BACKGROUND: Appropriate footwear is recommended for self-management of knee osteoarthritis. Shoes that reduce harmful knee loads are available, but symptomatic effects are uncertain. OBJECTIVE: To evaluate the efficacy of unloading shoes in alleviating knee osteoarthritis symptoms. DESIGN: Participant- and assessor-blinded comparative effectiveness randomized, controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12613000851763). SETTING: Community. PARTICIPANTS: 164 persons with medial knee osteoarthritis. INTERVENTION: Walking shoes with triple-density, variable-stiffness midsoles and mild lateral-wedge insoles designed to unload the medial knee and worn daily (intervention) versus conventional walking shoes (comparator). MEASUREMENTS: Primary outcomes were pain with walking (assessed on a numerical rating scale [NRS]) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) at 6 months. Secondary outcomes were knee pain and stiffness (WOMAC), average pain (NRS), intermittent and constant knee pain (Intermittent and Constant Osteoarthritis Pain questionnaire), quality of life (Assessment of Quality of Life instrument), physical activity (Physical Activity Scale for the Elderly), and global change in pain and function (Likert scales). RESULTS: A total of 160 participants (98%) completed primary outcome measures at 6 months. Changes in pain (mean difference, 0.0 units [95% CI, -0.9 to 0.8 unit]) and function (mean difference, 0.3 unit [CI, -3.2 to 3.7 units]) did not differ between groups at 6 months, with both groups showing clinically relevant improvements in function and the intervention group showing clinically relevant improvements in pain. There were no differences in secondary outcomes. Pain was globally improved in 54% of participants, and function was globally improved in 44% to 48%. Unloading shoes were not associated with increased probability of improvement (odds ratios, 0.99 [CI, 0.53 to 1.86] for pain and 0.85 [CI, 0.45 to 1.61] for function). LIMITATION: Effects on joint structure were not evaluated. CONCLUSION: Shoes with modified midsoles to unload the medial knee conferred no additional benefit over conventional walking shoes. Both improved pain and function by clinically relevant amounts. PRIMARY FUNDING SOURCE: Australian National Health and Medical Research Council. PMID- 27398992 TI - Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial. AB - RATIONALE: Studies have demonstrated that application of stress suppresses airway smooth muscle contractility. In animal models of asthma, continuous positive airway pressure (CPAP) reduced airway reactivity. Short-term studies of CPAP in patients with asthma showed reductions in airway reactivity. OBJECTIVES: To evaluate whether nocturnal CPAP decreased the provocative concentration of methacholine to reduce FEV1 by 20% (PC20). METHODS: One hundred ninety-four individuals with asthma were randomized (1:1:1) to use CPAP with warmed, filtered, humidified air at night at pressures either less than 1 cm H2O (sham) or at 5 cm H2O or 10 cm H2O. The primary outcome was change in PC20 after 12 weeks. MEASUREMENTS AND MAIN RESULTS: Adherence to CPAP was low in all groups. Regardless, all groups had a significant improvement in PC20, with 12 weeks/baseline PC20 ratios of 2.12, 1.73, and 1.78 for the sham, 5 cm H2O, and 10 cm H2O groups, respectively, and no significant differences between the active and sham groups. Changes in FEV1 and exhaled nitric oxide were minimal in all groups. The sham group had larger improvements in most patient-reported outcomes measuring asthma symptoms and quality of life, as well as sinus symptoms, than the 5 cm H2O group. The 10 cm H2O group showed similar but less consistent improvements in scores, which were not different from improvements in the sham group. CONCLUSIONS: Adherence to nocturnal CPAP was low. There was no evidence to support positive pressure as being effective for reducing airway reactivity in people with well-controlled asthma. Regardless, airway reactivity was improved in all groups, which may represent an effect of participating in a study and/or an effect of warm, humid, filtered air on airway reactivity. Clinical trial registered with www.clinicaltrials.gov (NCT01629823). PMID- 27398993 TI - Kinetic partitioning during de novo septin filament assembly creates a critical G1 "window of opportunity" for mutant septin function. AB - Septin proteins form highly conserved cytoskeletal filaments composed of hetero oligomers with strict subunit stoichiometry. Mutations within one hetero oligomerization interface (the "G" interface) bias the mutant septin toward conformations that are incompatible with filament assembly, causing disease in humans and, in budding yeast cells, temperature-sensitive defects in cytokinesis. We previously found that, when the amount of other hetero-oligomerization partners is limiting, wild-type and G interface-mutant alleles of a given yeast septin "compete" along parallel but distinct folding pathways for occupancy of a limited number of positions within septin hetero-octamers. Here, we synthesize a mathematical model that outlines the requirements for this phenomenon: if a wild type septin traverses a folding pathway that includes a single rate-limiting folding step, the acquisition by a mutant septin of additional slow folding steps creates an initially large disparity between wild-type and mutant in the cellular concentrations of oligomerization-competent monomers. When the 2 alleles are co expressed, this kinetic disparity results in mutant exclusion from hetero oligomers, even when the folded mutant monomer is oligomerization-competent. To test this model experimentally, we first visualize the kinetic delay in mutant oligomerization in living cells, and then narrow or widen the "window of opportunity" for mutant septin oligomerization by altering the length of the G1 phase of the yeast cell cycle, and observe the predicted exacerbation or suppression, respectively, of mutant cellular phenotypes. These findings reveal a fundamental kinetic principle governing in vivo assembly of multiprotein complexes, independent of the ability of the subunits to associate with each other. PMID- 27398994 TI - Pyrazolo[1,5-a]pyrimidine-based macrocycles as novel HIV-1 inhibitors: a patent evaluation of WO2015123182. AB - The emergence of drug resistance in Combination Antiretroviral Therapy (cART) confirms a continuing need to investigate novel HIV-1 inhibitors with unexplored mechanisms of action. Recently, a series of pyrazolopyrimidine-based macrocyclic compounds were reported as inhibitors of HIV-1 replication disclosed in the patent WO2015123182. Most of the disclosed compounds possessed in vitro antiviral potency in single-digit nanomolar range, which were determined by MT-2 cell assay. Then, the structural diversity, pharmacophore similarity of HIV-1 IN LEDGF/p75 inhibitors, and implications for drug design were analyzed. In the end of this article, a glimpse of some macrocycles as potent antiviral agents (drug candidates) was provided. Some strategies and technologies enabling macrocycle design were also described. We expect that further development of these macrocyclic compounds will offer new anti-HIV-1 drug candidates. PMID- 27398995 TI - Analysis of Lynch Syndrome Mismatch Repair Genes in Women with Endometrial Cancer. AB - OBJECTIVE: Endometrial cancer is the second most frequent neoplasm in women with Lynch syndrome (LS). We sought to assess whether analyzing women with endometrial cancer would identify families with LS not identified with current clinical criteria. METHODS: We included women diagnosed with endometrial cancer younger than 50 years and also older if they had a family cancer history associated with LS. In blood samples obtained, we analyzed mutations in mismatch repair (MMR) genes, as well as protein expression by immunohistochemistry and microsatellite instability (MSI) in tumour tissue. RESULTS: A total of 103 patients were enrolled. We detected 14 pathogenic mutations and 4 genetic variants of unknown clinical significance in MMR genes. We found MSI in 41.66% of the women with a pathogenic mutation. In this group, 76.92% showed loss of at least one MMR protein. Women with mutations were younger at diagnosis, but all of them had a family history compatible with LS. CONCLUSIONS: Analysis of the MMR genes, in particular MSH6, seems to be appropriate in women with endometrial cancer and a family history of tumours associated with LS. PMID- 27398996 TI - Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011. AB - OBJECTIVES: Sexual inequality starts in utero. The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. METHODS: Retrospective population-based study of 574,358 South Australian singleton live births during 1981-2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. RESULTS: The traditional approach showed male predominance for PTB [20-24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274-1.445], spontaneous PTB [25-29 weeks: RR M/F 1.118, 95%-CI 1.044-1.197%], GDM [RR M/F 1.042, 95%-CI 1.011-1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034-1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044-1.105]. The FAR approach showed that males were at increased risk for PTB [20-24 weeks: RR M/F 1.273, 95%-CI 1.087-1.490], for spontaneous PTB [25-29 weeks: RR M/F 1.269, 95%-CI 1.143-1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044-1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25-29 weeks: RR M/F 0.857, 95%-CI 0.780-0.941] and PIHD associated with PTB [25-29 weeks: RR M/F 0.686, 95% CI 0.581-0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25-29 weeks: RR M/F 0.779, 95%-CI 0.648-0.937]. CONCLUSIONS: This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene expression and function are likely to play a key role. Further research on sex differences in placental function and maternal adaptation to pregnancy is required to delineate the causal molecular mechanisms in sex-specific pregnancy outcome. Identifying these mechanisms may inform fetal sex specific tailored antenatal and neonatal care. PMID- 27398997 TI - Empirical Evidence of Study Design Biases in Randomized Trials: Systematic Review of Meta-Epidemiological Studies. AB - OBJECTIVE: To synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials. DESIGN: Systematic review of meta-epidemiological studies. METHODS: We retrieved eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR < 1 and dSMD < 0 denotes a larger intervention effect estimate in trials with an inadequate or unclear (versus adequate) characteristic. RESULTS: We included 24 studies. The available evidence suggests that intervention effect estimates may be exaggerated in trials with inadequate/unclear (versus adequate) sequence generation (ROR 0.93, 95% CI 0.86 to 0.99; 7 studies) and allocation concealment (ROR 0.90, 95% CI 0.84 to 0.97; 7 studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD -0.37, 95% CI -0.77 to 0.04; 2 studies), lack of/unclear blinding of outcome assessors (ROR 0.64, 95% CI 0.43 to 0.96; 1 study) and lack of/unclear double blinding (ROR 0.77, 95% CI 0.61 to 0.93; 1 study). The influence of other characteristics (e.g. unblinded trial personnel, attrition) is unclear. CONCLUSIONS: Certain characteristics of randomized trials may exaggerate intervention effect estimates. The average bias appears to be greatest in trials of subjective outcomes. More research on several characteristics, particularly attrition and selective reporting, is needed. PMID- 27398999 TI - Pistol ribozyme adopts a pseudoknot fold facilitating site-specific in-line cleavage. AB - The field of small self-cleaving nucleolytic ribozymes has been invigorated by the recent discovery of the twister, twister-sister, pistol and hatchet ribozymes. We report the crystal structure of a pistol ribozyme termed env25, which adopts a compact tertiary architecture stabilized by an embedded pseudoknot fold. The G-U cleavage site adopts a splayed-apart conformation with in-line alignment of the modeled 2'-O of G for attack on the adjacent to-be-cleaved P-O5' bond. Highly conserved residues G40 (N1 position) and A32 (N3 and 2'-OH positions) are aligned to act as a general base and a general acid, respectively, to accelerate cleavage chemistry, with their roles confirmed by cleavage assays on variants, and an increased pKa of 4.7 for A32. Our structure of the pistol ribozyme defined how the overall and local topologies dictate the in-line alignment at the G-U cleavage site, with cleavage assays on variants revealing key residues that participate in acid-base-catalyzed cleavage chemistry. PMID- 27398998 TI - Conformationally selective RNA aptamers allosterically modulate the beta2 adrenoceptor. AB - G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However, stabilizing distinct active GPCR conformations to enable structural characterization of mechanisms underlying GPCR activation remains difficult. These challenges have accentuated the need for receptor tools that allosterically stabilize and regulate receptor function through unique, previously unappreciated mechanisms. Here, using a highly diverse RNA library combined with advanced selection strategies involving state-of-the-art next generation sequencing and bioinformatics analyses, we identify RNA aptamers that bind a prototypical GPCR, the beta2-adrenoceptor (beta2AR). Using biochemical, pharmacological, and biophysical approaches, we demonstrate that these aptamers bind with nanomolar affinity at defined surfaces of the receptor, allosterically stabilizing active, inactive, and ligand-specific receptor conformations. The discovery of RNA aptamers as allosteric GPCR modulators significantly expands the diversity of ligands available to study the structural and functional regulation of GPCRs. PMID- 27399000 TI - A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines. AB - More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remained mysterious. Here, we use activity-based protein profiling to identify the poorly characterized serine hydrolase PLA2G4E as a mouse brain Ca-NAT and show that this enzyme generates NAPEs and NAEs in mammalian cells. PMID- 27399002 TI - Is it possible to revert doctor-patient relationship deterioration? PMID- 27399001 TI - Expression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidate. AB - Chikungunya virus (CHIKV) has emerged as a global health concern due to its recent spread in both old and new world. So far, no CHIKV specific drug or vaccine is licensed for human use. In this study, we report production of Chikungunya virus like particles (CHIK-VLPs) using novel yeast expression system (Pichia pastoris) and its evaluation as vaccine candidate. The gene encoding structural polyprotein of CHIKV from a recent epidemic strain was cloned into yeast expression system. The multicopy integrants were processed for expression of CHIK-VLPs. The VLPs were purified and confirmed through electron microscopic analysis for their morphological identity with CHIKV. The in vitro and in vivo evaluation of CHIK-VLPs as vaccine candidate was determined in Balb/c mice. Induction of both humoral and cellular immune response was observed with different doses of CHIK-VLPs. The humoral immune response was studied through different techniques like enzyme linked immunosorbent assay, IgG Isotyping and plaque reduction neutralization test. CHIK-VLPs were found to elicit high titer of antibodies that are able to recognize native CHIKV. Higher level of IgG2a and IgG1 subtypes was identified suggestive of balanced Th1/Th2 response. Both in vitro and in vivo neutralization activity of CHIK-VLPs antibodies was observed even with low concentration, which shows its high specificity and neutralizing activity against two different CHIKV strains. Neonatal mice receiving anti-CHIK VLPs antibodies were protected from CHIKV challenge. Induction of cellular immune response was confirmed through higher level of TNF-alpha, IL-10 and substantial level of IL-2, IL-4 and IFN-gamma indicating a balanced response. This is the first report, where CHIK-VLPs has been expressed by Pichia pastoris and evaluated for neutralizing activity against CHIKV. These promising results indicate the utility of CHIK-VLPs as a promising vaccine candidate against emerging CHIKV. PMID- 27399003 TI - Art as a vital human function. PMID- 27399004 TI - Nothing is certain... A comment on uncertainty, objectivity and scientism. PMID- 27399005 TI - The National Network of Congenital Anomalies: extended goals for surveillance. PMID- 27399006 TI - Opinions of members of the National Civil (Family Proceedings) and Criminal Courts in withholding or withdrawing of life support situations in pediatrics. AB - INTRODUCTION: The possibility of sustaining life functions makes it difficult to distinguish between a dying patient and a patient with chances of survival, raising a dilemma for everyone around them. On the one side, continuing with life support techniques that would only extend an irreversible process and result in physical and psychological damage and harm their dignity. On the other side, withholding or withdrawing life support without an adequate reflection and diagnostic-therapeutic effort which may lead to the death of a potentially recoverable child. In addition, making decisions in this context implies facing barriers that hinder the possibility of pursuing the patient's best interest. Among such barriers, the fear of litigation plays a major role. To what extent is this fear justified? OBJECTIVE: To explore the opinions of the members of the National Judiciary regarding the approach to withholding or withdrawing of life support from a legal stance. POPULATION AND METHODS: Professionals working in the criminal, civil and forensic medicine settings. Semistructured survey on three hypothetical case histories that implied making a decision to withhold or withdraw life support. RESULTS: One hundred and eighty-five surveys were distributed; 68 (36.76%) were partially completed and 51 (30.3%), in full. Twenty eight (55%) survey respondents did not criminalize any of the three cases presented. Thirteen (25%) respondents considered that the decisions made in the three cases constituted a crime; 6 (12%), only in one case; and 4 (8%), in two out of the three. Crimes described by survey respondents included intentional homicide, wrongful death, and failure to render assistance. CONCLUSIONS: Forty five percent of survey respondents considered that decisions made involved some form of crime. PMID- 27399007 TI - Efficacy and safety of caspofungin in children: systematic review and meta analysis. AB - INTRODUCTION: Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. OBJECTIVE: To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. MATERIALS AND METHODS: The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. RESULTS: The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. CONCLUSIONS: This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions. PMID- 27399008 TI - Fluid balance and length of mechanical ventilation in children admitted to a single Pediatric Intensive Care Unit. AB - INTRODUCTION: Associations between cumulative fluid balance and a prolonged duration of assisted mechanical ventilation have been described in adults. The aim of this study was to evaluate whether fluid balance in the first 48 hours of assisted mechanical ventilation initiation was associated with a prolonged duration of this process among children in the Pediatric Intensive Care Unit (PICU). METHODS: Retrospective cohort of patients in the PICU o, Hospital Italiano de Buenos Aires, between 1/1/2010 and 6/30/2012. Balance was calculated in percentage of body weight; prolonged mechanical ventilation was defined as >7 days, and confounders were registered. Univariate and multivariate analyses were performed. RESULTS: Two hundred and forty-nine patients were mechanically ventilated for over 48 hours; 163 were included in the study. Balance during the first 48 hours of mechanical ventilation was 5.7% +/- 5.86; 82 patients (50.3%) were on mechanical ventilation for more than 7 days. Age < 4 years old (OR 3.21, 95% CI 1.38-7.48, p 0.007), respiratory disease (OR 4.94, 95% CI 1.51-16.10, p 0.008), septic shock (OR 4.66, 95% CI 1.10-19.65, p 0.036), Pediatric Logistic Organ Dysfunction (PELOD) > 10 (OR 2.44, 95% CI 1.234.85, p 0.011), and positive balance > 13% (OR 4.02, 95% CI 1.08-15.02, p 0.038) were associated with prolonged mechanical ventilation. The multivariate model resulted in an OR 2.58, 95% CI: 1.17-5.58, p= 0.018 for PELOD > 10, and an OR 3.7, 95% CI: 0.91-14.94, p= 0.066 for positive balance > 13%. CONCLUSIONS: Regarding prolonged mechanical ventilation, the multivariate model showed an independent association with organ dysfunction (PELOD > 10) and a trend towards an association with positive balance > 13%. PMID- 27399009 TI - Assessment of self-perception of physical fitness and proposal for standards among Chilean adolescent students: the EAPAF study. AB - INTRODUCTION: Physical fitness may be assessed among children and adolescents in a quantitative and qualitative manner. At present, in Chile, there are no tools available to assess self-perception of physical fitness. Therefore, the purpose of this study was to develop a valid and reliable instrument that would allow to assess selfperception of physical fitness among adolescents and propose standards for age and sex. MATERIALS AND METHODS: A survey was administered among adolescent students from six public schools in the Maule Region, Chile, selected in a probabilistic (stratified) fashion. To measure self-perception of physical fitness, a qualitative instrument was developed: the Self-Perception of Physical Fitness Scale (EAPAF, escala de autopercepcion de la aptitud fisica), which is made up of four dimensions and 18 questions. The LMS method (L: Box-Cox coefficient, M: median curve, and S: variation coefficient) was used to establish percentiles and propose references by dimension, age and sex. RESULTS: A total of 3060 adolescents (1702 boys and 1358 girls) aged 11.0 to 18.9 years old were included. The factor analysis evidenced four factors. Saturation values were above 0.40. The percentage of instrument explanation reached 54.24%. In terms of reliability, the 18 questions reflected that Cronbach's alpha was between 0.82 and 0.85. Percentiles (p15, p50 and p85) were developed to classify self perception of physical fitness by dimension, age and sex. Boys showed higher scores in the self-perception of physical fitness scale when compared to girls (p < 0.001). CONCLUSION: The instrument developed in this study was valid and reliable. In addition, the standards proposed may become a useful tool to classify adolescents in relation to their selfperception of physical fitness. PMID- 27399010 TI - Insulin level and insulin sensitivity indices among healthy children and adolescents. AB - INTRODUCTION: Information on insulin reference values and insulin sensitivity indices in the field of pediatrics is scarce. OBJECTIVE: To describe insulin range and insulin sensitivity surrogate indices during childhood. MATERIALS AND METHODS: Fasting insulin level range and surrogate indices, such as the homeostasis model assessment of insulin resistance (HOMA-IR), among healthy children and adolescents by age, body mass index, pubertal stage (PS), insulin like growth factor-1 (IGF-1), total cholesterol, and triglycerides. RESULTS: Two hundred and twenty-six healthy children and adolescents (1-18 years old) were included. Insulin increased with age, body mass index, pubertal stage, IGF-1 and triglyceride levels (r2= 0.38, p < 0.0001). Prepubertal children > 7.5 years old had higher insulin levels [median (P3 and P97) pIU/mL: 5.0 (1.7-9.6)] than prepubertal children < 7.5 years old [2.9 pIU/ mL (1.3-10.9), p < 0.01]. During puberty (from PS II to PS V), insulin was higher in girls than in boys [7.4 (1.8 16.9) versus 5.8 (1.8-12.9), p < 0.01]. The HOMA-IR index increased in the group of prepubertal children > 7.5 years old: 1.1 (0.32.0) versus children < 7.5 years old: 0.6 (0.3-1.4, p < 0.01). The insulin level and HOMA-IR results were higher in pubertal children compared to the prepubertal group (p < 0.001). CONCLUSIONS: Known physiological changes were observed inboth insulin levels and the HOMA-IR index among children and adolescents. A fasting blood insulin level of 10 pIU/mL in prepubertal children and of 17 pIU/mL and 13 pIU/mL in pubertal girls and boys, respectively, may be considered as an acceptable cut-off value in healthy children. A HOMA-IR value > 2.0 and > 2.6 in prepubertal and pubertal children, respectively, may be considered a warning sign for pediatricians to further investigate insulin resistance. PMID- 27399011 TI - Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina. AB - INTRODUCTION: Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. POPULATION AND METHODS: Retrospective cohort made up of 140 transplant patients a, Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value < 0.05 was considered significant. RESULTS: The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01). CONCLUSIONS: The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting. KEY WORDS: comorbidity, hematopoietic stem cell transplantation, non-relapse mortality, pediatrics. PMID- 27399012 TI - Are red blood cell transfusions associated with nosocomial infections in critically ill children? AB - Although the transfusionofblood products is common practice, its effects on the immune system have not been adequately studied. A prospective cohort study was conducted in critically ill children followed up until their death, transfer or discharge to establish an association between red blood cell transfusions (RBCTs) and nosocomial infections. A nosocomial infection was considered to be post transfusional if it occurred within 14 days after RBCT. A total of 162 children were included in the study, 35 (21.6%) had a nosocomial infection, and 49 (30.2%) received a RBCT. Among those with a nosocomial infection, a RBCT was more common (48.5% versus 14.9%, OR: 5.4, 95% CI: 2.412.6, p < 0.0001) and mortality rate was higher (45.7% versus 10.2%, OR: 7.4, 95% CI: 3.1-18.2, p < 0.0001). The binary logistic regression showed that RBCT was independently associated with nosocomial infections (OR: 4.2, 95% CI: 2.1-20.2, p = 0.049). CONCLUSION: RBCT was associated with increased risk for nosocomial infections. PMID- 27399013 TI - [Publication of abstracts presented at the National Pediatric Research Meetings of the Argentine Society of Pediatrics: Related factors]. AB - OBJECTIVE: To estimate the proportion of abstracts presented at National Pediatric Research Meetings that are fully-published and describe their design and factors that influence nonpublication. METHODS: Descriptive and analytical study including all abstracts presented at National Pediatric Research Meetings (1998-2011). One author per study was identified and asked to complete a survey on its design, publication and factors associated with non-publication. RESULTS: Out of 746 abstracts that were submitted, the authors of 522 (70%) completed the survey. Among these, 84.3% were observational studies and 15.7%, experimental; 34% had received funding. Two hundred and seventeen abstracts were published subsequently (41.5%, 95% confidence interval [CI]: 37.3-45.9). Funded studies had better chances of being published (odds ratio [OR]: 2, 95% CI: 1.4-2.9, p < 0.001). Lack of time, insufficient sample size, and problems with funding were referred as the most common reasons for failure to publish. CONCLUSIONS: Among allabstracts presented at National Pediatric Research Meetings, 41.5% were fully published. Lack of time was the most common reason for unpublished studies. PMID- 27399014 TI - Rights of persons with conditions associated with disability: current legal framework. AB - The objective of this review study is to promote the dissemination of the legislation in force in Argentina for the protection of the rights of persons with conditions that might cause disability. Articles of bills and laws that protect the rights of these families are reviewed, so that health care providers assisting them have better access to them. Argentina has a wide range of laws and regulations dedicated to protecting them, but they are generally not clearly recognized by citizens. The aim is to disseminate this information in the medical setting so that health care providers can help patients recognize their rights through empowerment. PMID- 27399015 TI - Neonatal intensive care unit lighting: update and recommendations. AB - Achieving adequate lighting in neonatal intensive care units is a major challenge: in addition to the usual considerations of visual performance, cost, energy and aesthetics, there appear different biological needs of patients, health care providers and family members. Communicational aspects of light, its role as a facilitator of the visual function of doctors and nurses, and its effects on the newborn infant physiology and development were addressed in order to review the effects of light (natural and artificial) within neonatal care with a focus on development. The role of light in regulating the newborn infant circadian cycle in particular and the therapeutic use of light in general were also reviewed. For each aspect, practical recommendations were specified for a proper well-lit environment in neonatal intensive care units. PMID- 27399016 TI - [Excessive crying in infants in the first months of life: review]. AB - Cry-fuss problems are among the most common clinical presentations in the first few months of life. Cry-fuss behaviour emerges out of a complex interplay of cultural, psychosocial, environmental and biologic factors, with organic disturbance implicated in only 5% of cases. A holistic biopsychosocial approach can be most effective. This article reviews recent evidence to update clinical management, and will attempt to reconceptualize infant colic definition. PMID- 27399017 TI - [Urticaria pigmentosa: clinical and therapeutic aspects for the paediatrician]. AB - Urticaria pigmentosa, also known as maculopapular mastocytosis, is the most common type of paediatric mastocytosis. It presents with yellow to brown macules or papules, usually located on trunk and extremities. Regarding its diagnostic and therapeutic implications, the objective of this article is to serve as an update for the paediatrician on the most relevant aspects of this pathology. PMID- 27399018 TI - [Kawasaki disease: interdisciplinary and intersocieties consensus (clinical guidelines). Brief version]. AB - Kawasaki disease is an acute self-limiting systemic vasculitis. It is the most common cause of acquired heart disease, with the risk of developing coronary artery aneurysms, myocardial infarction and sudden death. Diagnosis is based on the presence of fever in addition to other clinical criteria. The quarter of the Kawasaki disease patients have "incomplete" presentation. Treatment with intravenous immunoglobulin within ten days of fever onset improves clinical outcomes and reduces the incidence of coronary artery dilation to less than 5%. Non-responders to standard therapy have shown a successful response with the use of corticosteroids and/or biological agents. The long-term management must be delineated according to the degree of coronary involvement in a multidisciplinary manner. To facilitate the pediatrician's diagnosis, treatment and monitoring of Kawasaki disease, a group of experts from the Argentine Society of Pediatrics and the Argentine Society of Cardiology carried out a consensus to develop practical clinical guidelines. PMID- 27399019 TI - Concurrent validity and interobserver reliability of the EPInfant pediatric perceived exertion rating scale among healthy Chilean children. AB - The objective of this study was to determine the validity and reliability of the EPInfant pediatric perceived exertion rating scale among Chilean children. Children aged 8-12 years old were selected; their heart rate, perceived exertion and workload were recorded during two consecutive Chester tests performed with a one week interval. Pearson's r coefficient and the intraclass correlation coefficient were estimated. Thirty-one children (17 boys) were included in the study. A strong correlation was observed between perceived exertion and reference criteria, in addition to a high intraclass correlation coefficient. The average difference between the perceived exertion in each test was 1.4 (95% CI: -1.4 to 4.1) and 0.2 (95% CI: -1.8 to 2.2) for boys and girls, respectively. The EPInfant scale showed an acceptable criterion validity and interobserver reliability among children during an incremental step test. PMID- 27399020 TI - [Severe infection by methicillin sensitive Staphylococcus aureus producing Panton Valentine leukocidin: reports of two cases]. AB - Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria. PMID- 27399021 TI - [Melkersson Rosenthal syndrome. Report of two pediatric cases]. AB - Melkersson Rosenthal syndrome is a very infrequent disease of unknown etiology, chronic and progressive course, with neurocutaneous disease that affects the orofacial innervation and mucocutaneous tissues with non-caseating granulomatous infiltration. Clinically, it is characterized by the diagnostic triad: recurrent edema of lips and/or face; recurrent and alternating acute peripheral facial paralysis and scrotal or geographic tongue. The condition generally presents as oligosymptomatic or monosymptomatic form. Two patients are presented with completed triad and oligosymptomatic form. This recent review published by G. Kayabasoglu et al. states that only 30 patients have been described in the international literature in childhood. So we consider this disease in the differential diagnosis in the presence of acute peripheral facial paralysis and/or lips or facial edema. PMID- 27399022 TI - [Langer-Giedion syndrome with 8q23.1-q24.12 deletion diagnosed by comparative genomic hybridization]. AB - The Langer-Giedion syndrome, also known as trichorhinophalangeal syndrome type II, is a hereditary multisystemic disease part of the group of contiguous gene deletion syndromes. The cause of this syndrome is a heterozygous deletion that involves the chromosomal region 8q23.3-q24.11 and mainly affects genes TRPS1, RAD21, and EXT1. This syndrome is characterized by the presence of multiple osteochondromas in limbs, hypertrichosis, and facial phenotype that includes sparse scalp hair, large laterally protruding ears, a long nose with a bulbous tip. We report the case of a Colombian patient with finding of an 8q23.1-q24.12 deletion by comparative genomic hybridization array technique and classical clinical findings, being the first case reported in Colombia. PMID- 27399023 TI - [Pulmonary actinomycosis and tuberculosis. A comorbidity pediatric case]. AB - Actinomycosis is a chronic suppurative infection, produced by anaerobic Gram positive bacteria or microaerobic Actinomyces species. It is rare in children and adolescents and it is more common in immunocompromised. Mycobacterium tuberculosis collaborates on the development of the disease. Pulmonary involvement appears as a picture of chronic condensation that does not improve with conventional antibiotic treatment. Classic complications affecting the thoracic wall with drainage in "sulfur granule" and fistulization are described less frequently nowadays. The diagnosis is a real challenge and it is set by using the isolation of species of Actinomyces. The treatment of choice for all clinical forms of the disease is the prolonged use of antibiotics. OBJECTIVE: to present a pediatric case of comorbidity between tuberculosis and actinomycosis and to highlight the importance of diagnostic suspicion of actinomycosis in the presence of all chronic suppurative processes. PMID- 27399024 TI - [Nummular dermatitis: report of two cases in children]. AB - Nummular eczema or dermatitis is an uncommon paediatric pathology. It is presented as red-purplish small papules and vesicles that join to form exudative circular patches and then to eczematous or lichenified patches with discoid shape. The lesions appear predominantly on the extensor surface of extremities, although they can appear in trunk, hands or feet. This pathology has a clinical diagnosis; only few cases require complementary test. The topical corticosteroids are the mainstay of the treatment, and the causal treatment whether an infectious trigger is found. The patients have chronic or recurrent evolution. We report two cases in children with the aim of spreading knowledge among pediatricians. PMID- 27399025 TI - Pulmonary complications of chemical pneumonia: a case report. AB - Hydrocarbon aspiration (HA) can cause significant lung disease by inducing an inflammatory response, hemorrhagic exudative alveolitis, and loss of surfactant function. The most serious side effect of HA is aspiration pneumonia. Pneumothorax, pneumatocele, acute respiratory distress syndrome (ARDS), pulmonary abscess, bronchopleural fistula, bilateral hemorrhagic pleural effusion and pyopneumothorax were previously reported. Hereby we report a patient hospitalized due to aspiration pneumonia who developed pleurisy and pneumothorax after drinking paint thinner. It is presented as it was seldom reported in children to cause distinct pulmonary complications. Patients with complaints associated withhydrocarbon poisoning must be fully evaluated. They must not be discharged from the hospital early and must be followed for at least 48 hours even if they don't have respiratory symptoms. It should be kept in mind that severe pulmonary complications can develop in patients with chemical pneumonia. PMID- 27399026 TI - [Henoch-Schonlein purpura involving the penis: a case report]. AB - Schonlein-Henoch purpura accounts for the majority of cases of systemic vasculitis in children. Classical presentation is characterized by palpable purpura, glomerulonephritis, arthralgias and abdominal pain. Although genitourinary manifestations, in form of testicular and scrotal involvement, have been widely described, penile involvement remains an extremely rare complication. We report a case of a 6-year-old boy who presented with purpuric rash on the glans, prepuce and penile shaft, with painful edema in the penile region. He also had a 3-days history of fever, palpable purpuric rash on the buttocks and lower extremities along with right wrist pain. He was admitted with the diagnosis of Schonlein-Henoch purpura with penile involvement. After 2 days on oral steroids therapy (prednisone) a marked improvement was observed. PMID- 27399027 TI - [Azathioprine-induced pancytopenia: case series]. AB - Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts. In patients with fever and severe neutropenia, early empirical antibiotic treatment should be initiated to prevent severe and disseminated infection. Two patients with this condition are reported. PMID- 27399028 TI - [Langerhans cell histiocytosis with vertebral involvement and soft tissue extension: clinical case]. AB - Langerhans cell histiocytosis is a heterogeneous disease of unknown etiology characterized by proliferation of Langerhans cells. It is a rare disease. Bone involvement is common but vertebral disease is rare. We present a 4 year old patient with abdominal pain and neurologic symptoms. Magnetic resonance showed vertebra plana in D9 with involvement of paravertebral soft tissues. The child underwent surgery for decompression and biopsy. Biopsy confirmed Langerhans cell histiocytosis. She was treated with vinblastine and prednisone during 6 months following LCH-III with complete recovery of neurologic symptoms. CONCLUSION: Langerhans cell histiocytosis is a differential diagnosis in a radiograph with vertebra plana or collapse of vertebral body. PMID- 27399029 TI - Calcaneus osteomyelitis secondary to Guthrie test: case report. AB - Calcaneus osteomyelitis is a rare infection in newborns. Invasive procedures, prematurity and low birth wight are some causative factors. The clinical signs may be mild. We report a neonate with calcaneous osteomyelitis which was secondary to a Guthrie test sample. She was admitted to hospital with swelling, redness and increased temperature on her heel. Superficial tissue ultrasound showed fluid collection with heavy content was observed on the posterior of the right foot. Puncture and drainage was performed and methicillin-susceptible Staphylococcus aureus was isolated from the drainage culture. Extremity magnetic resonance imaging showed tissue defect in right foot, edema-inflammation and contrast enhancement. Intravenous sulbactam-ampicillin and oral amoxicillin and clavulanic acid were given for 6 weeks. In follow-up, clinical symptoms recovered without curettage. In conclusion; calcaneous osteomyelitis should be considered in the differential diagnosis of swelling on heel in neonates who have been applied to invasive procedures as Guthrie test sample. PMID- 27399030 TI - [Langerhans cell histiocytosis presenting as isolated adenitis in an infant: case report]. AB - Langerhans cell histiocytosis in infants is a rare condition, and presentation as an isolated cervical adenitis is exceptional at this age. We describe the case of a 3-month-old female infant presenting with a neck mass in the right mandibular angle with poor response to antibiotic treatment. Fine needle aspiration was performed and confirmed the diagnosis of Langerhans cell histiocytosis with complementary tests showing no features of systemic involvement. Langerhans cell histiocytosis should be considered in the differential diagnosis of subacute neck masses with poor outcome in infants and physicians should consider performing a fine needle aspiration to establish the diagnosis. PMID- 27399031 TI - [Saint Louis encephalitis: case report]. AB - Saint Louis encephalitis is transmitted by Culex mosquitoes. In Argentina sporadic cases are registered. Symptomatic illness is unusual in children. We present a case of meningoencephalitis caused by an uncommon viral infection. The clinical signs and symptoms are unusual for pediatric patients and the bilateral thalamic compromise showed on magnetic resonance has not been described previously. An 8-year-old girl consulted due to fever, behavior disorders and ataxia. Clonus and neck stiffness were detected at physical exam. Cerebrospinal fluid revealed mononuclear leukocytosis; bilateral ischemic compromise was observed in thalamus by magnetic resonance. Saint Louis virus was confirmed by serology: serum and cerebrospinal fluid IgM were positive during the acute phase of the disease and serum IgG was positive four weeks later. Most of the signs and symptoms of the disease were resolved, however mild behavior disorders were observed as acute sequelae up to 45 days after hospital discharge. PMID- 27399032 TI - The defense response and alcohol intake: A coronary artery disease risk? The SABPA Study. AB - The behavioral defense coping response (DefS) as a measure of coping with emotional stress may increase alcohol intake (gamma glutamyl transferase (gammaGT)), the risk for coronary artery disease (CAD) and insulin sensitivity (homeostasis model assessment, HOMA). We assessed associations between coping and cardiometabolic risk markers in a bi-ethnic cohort (N = 390) from South Africa. Ambulatory blood pressure (BP) and ECG, fasting blood and coping scores were obtained. Africans, and mostly when utilizing DefS, showed higher 24h BP, a low grade inflammatory state, central obesity, increased HOMA [4.07 (3.66, 4.47)] and more ST events compared to their Caucasian counterparts. ROC gamma-GT analyses predicting 24-h ambulatory hypertension showed a higher gamma-GT cut-point in Africans (55.4 U/l) than in Caucasians (19.5 U/l). Odds ratios (ORs) of gamma-GT cut-points predicting 24-h ambulatory hypertension was evident in DefS African men [OR: 7.37 (95% CI: 6.71-8.05), p = 0.003] and in DefS Caucasians, albeit at a lower gamma-GT cut-point (19.5 U/l). Higher gamma-GT cut-points in DefS Africans or Caucasians were not associated with HOMA > 3. DefS accompanied by alcohol abuse in taxing emotional situations, if no social support is forthcoming, underscores a profile of reduced coronary perfusion. It may enhance vasoconstriction of the coronary arteries, with compensatory increases in BP, and induce a risk for future coronary artery disease. PMID- 27399033 TI - Design of the Hospital Integrated Information Management System Based on Cloud Platform. AB - At present, the outdated information management style cannot meet the needs of hospital management, and has become the bottleneck of hospital's management and development. In order to improve the integrated management of information, hospitals have increased their investment in integrated information management systems. On account of the lack of reasonable and scientific design, some hospital integrated information management systems have common problems, such as unfriendly interface, poor portability and maintainability, low security and efficiency, lack of interactivity and information sharing. To solve the problem, this paper carries out the research and design of a hospital information management system based on cloud platform, which can realize the optimized integration of hospital information resources and save money. PMID- 27399035 TI - Influence of Grafting Point Distribution on the Surface Structures of Y-Shaped Polymer Brushes in Solution. AB - We report a simulated annealing study of surface structures of the Y-shaped copolymers grafted onto a planar substrate in nonselective solvents. The influences of the lateral size of the grafting surface and the distribution manner of the grafting point on the order degree of the ripple structures are investigated. Under uniformly distribution conditions, it is found that the well defined ripple structures can be formed when the lateral size less than a threshold which depends on the solvent quality and grafting density. However, introducing a density fluctuation into the uniformly distribution grafting points in different ways, the defects with different degrees are observed in the ripple structures. The influence of the density fluctuations on the ripple phase are studied quantitatively. Furthermore, the possibility of the formation of surface structures with long-range order induced by directed self-assembly is investigated. The findings provide guidelines for fabricating patterned surfaces with highly ordered structures. PMID- 27399036 TI - Large-Scale Metabolite Analysis of Standards and Human Serum by Laser Desorption Ionization Mass Spectrometry from Silicon Nanopost Arrays. AB - The unique challenges presented by metabolomics have driven the development of new mass spectrometry (MS)-based techniques for small molecule analysis. We have previously demonstrated silicon nanopost arrays (NAPA) to be an effective substrate for laser desorption ionization (LDI) of small molecules for MS. However, the utility of NAPA-LDI-MS for a wide range of metabolite classes has not been investigated. Here we apply NAPA-LDI-MS to the large-scale acquisition of high-resolution mass spectra and tandem mass spectra from a collection of metabolite standards covering a range of compound classes including amino acids, nucleotides, carbohydrates, xenobiotics, lipids, and other classes. In untargeted analysis of metabolite standard mixtures, detection was achieved for 374 compounds and useful MS/MS spectra were obtained for 287 compounds, without individual optimization of ionization or fragmentation conditions. Metabolite detection was evaluated in the context of 31 metabolic pathways, and NAPA-LDI-MS was found to provide detection for 63% of investigated pathway metabolites. Individual, targeted analysis of the 20 common amino acids provided detection of 100% of the investigated compounds, demonstrating that improved coverage is possible through optimization and targeting of individual analytes or analyte classes. In direct analysis of aqueous and organic extracts from human serum samples, spectral features were assigned to a total of 108 small metabolites and lipids. Glucose and amino acids were quantitated within their physiological concentration ranges. The broad coverage demonstrated by this large-scale screening experiment opens the door for use of NAPA-LDI-MS in numerous metabolite analysis applications. PMID- 27399037 TI - Evaluation of the Relationship between Childhood Traumas and Adulthood Obesity Development. AB - This study aimed to delineate the relationship between childhood traumas and adulthood obesity. A total of 314 individuals (157 obese and 157 nonobese) were recruited in the study. After obtaining anthropometric and sociodemographic variables, the Childhood Trauma Questionnaire (CTQ) was administered to the participants. Overall scores of CTQ were determined to be 42.6 +/- 10.5 (higher trauma) in obese group and 37.2 +/- 6.6 (lower trauma) in nonobese group (P < 0.001). Frequency rates of childhood traumatic experience were found to be 68.8% for obese people and 38.8% for nonobese people. In conclusion, an increased risk for adulthood obesity development was significantly associated with childhood traumatic experience. PMID- 27399038 TI - Low-Temperature Reactivity of C2n+1N(-) Anions with Polar Molecules. AB - Following the recent discovery of molecular anions in the interstellar medium, we report on the kinetics of proton transfer reactions between cyanopolyynide anions C2n+1N(-) (n = 0, 1, 2) and formic acid HCOOH. The results, obtained from room temperature down to 36 K by means of uniform supersonic flows, show a surprisingly weak temperature dependence of the CN(-) reaction rate, in contrast with longer chain anions. The CN(-) + HCOOH reaction is further studied theoretically via a reduced dimensional quantum model that highlights a tendency of the reaction probability to decrease with temperature, in agreement with experimental data but at the opposite of conventional long-range capture theories. In return, comparing HCOOH to HC3N as target molecules suggests that dipole-dipole interactions must play an active role in overcoming this limiting effect at low temperatures. This work provides new fundamental insights on prototypical reactions between polar anions and polar molecules along with critical data for astrochemical modeling. PMID- 27399039 TI - Strengthening HIV surveillance: measurements to track the epidemic in real time. AB - Surveillance for HIV as a public health initiative requires timely, detailed and robust data to systematically understand burden of infection, transmission patterns, direct prevention efforts, guide funding, identify new infections and predict future trends in the epidemic. The methods for HIV surveillance have evolved to reliably track the epidemic and identify new infections in real time. Initially HIV surveillance relied primarily on the reporting of AIDS cases followed by measuring antibodies to HIV to determine prevalence in key populations. With the roll-out of antiretroviral therapy (ART) resulting in better survival and the corresponding increase in HIV prevalence, the landscape of surveillance shifted further to track HIV prevalence and incidence within the context of programmes. Recent developments in laboratory assays that potentially measure and differentiate recent versus established HIV infection offer a cost effective method for the rapid estimation of HIV incidence. These tests continue to be validated and are increasingly useful in informing the status of the epidemic in real time. Surveillance of heterogeneity of infections contributing to sub-epidemics requires methods to identify affected populations, density, key geographical locations and phylogenetically linked or clustered infections. Such methods could provide a nuanced understanding of the epidemic and prioritise prevention efforts to those most vulnerable. This paper brings together recent developments and challenges facing HIV surveillance, together with the application of newer assays and methods to fast-track the HIV prevention and treatment response. PMID- 27399040 TI - Choice in HIV testing: the acceptability and anticipated use of a self administered at-home oral HIV test among South Africans. AB - Combination HIV prevention is being widely promoted by funders. This strategy aims to offer HIV prevention choices that can be selected and combined to decrease HIV risk in ways that fit with each individual's situation. Treatment as prevention and pre-exposure prophylaxis are two new evidence-based strategies to decrease HIV incidence, both of which require high HIV testing rates to be effective, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a goal of 90% of HIV-positive individuals knowing their status by 2030. However, HIV testing rates in many countries remain suboptimal. Just as no single HIV prevention method is ideal for all people in all situations, no single HIV testing modality is likely to be acceptable to everyone. By offering HIV testing choices, we may be able to increase testing rates. However, many low-resourced countries have been slow to take up new HIV testing options such as the self administered at-home oral HIV test that is currently available in the United States. In this paper, we present findings from 20 in-depth interviews, conducted in 2010, documenting opinions about self-administered at-home oral HIV testing, a testing modality still largely unavailable in Africa. Participants were clients of three primary healthcare clinics in South Africa. Self-testing was seen as enabling confidentiality/privacy, saving time, and facilitating testing together with partners. However, concerns were raised about psychological distress when testing at home without a counsellor. Some suggested this concern could be minimised by having experienced clinic-based HIV testing and counselling before getting self-testing kits for home use. Thus, self-administered HIV testing could be an option added to the current testing modalities to address some important barriers to testing. PMID- 27399041 TI - Combination HIV prevention options for young women in Africa. AB - Although the number of new HIV infections has declined by over 30% in the past decade, the number of people who acquire HIV each year remains unacceptably high. In 2014 the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that there were about 2 million new HIV infections. The virus continues to spread, particularly in key populations, such as men who have sex with men (MSM), transgender individuals, sex workers and people who inject drugs. In Africa, young women have the highest HIV incidence rates. Scaling up known efficacious HIV prevention strategies for these groups at high risk is therefore a high priority. HIV prevention has generally been targeted at HIV-negative individuals or in some instances, entire communities. Prevention efforts are, however, shifting from a narrow focus on HIV-uninfected persons to a continuum of prevention that includes both HIV-negative and HIV-positive individuals. Given that a single HIV prevention intervention is unlikely to be able to alter the epidemic trajectory as HIV epidemics in communities are complex and comprise a mosaic of different risk factors and different routes of transmission, there is need to provide combination prevention. Hence, a mix of behavioural, biomedical and structural HIV prevention options is likely to be needed to alter the course of the HIV epidemic. The combination of HIV prevention interventions needed will vary depending on cultural context, the population targeted and the stage of the epidemic. This paper reviews the available HIV prevention strategies for young women and discusses new HIV prevention approaches in development. PMID- 27399043 TI - Tackling gender inequalities and intimate partner violence in the response to HIV: moving towards effective interventions in Southern and Eastern Africa. AB - Ending intimate partner violence (IPV) and reducing gender inequalities are recognised as critical to "'ending AIDS" by 2030. Amongst women, experiencing IPV has been shown to increase HIV acquisition, reduce women's ability to use HIV prevention strategies and reduce adherence to antiretroviral therapy (ART). In Southern and Eastern Africa there has recently been a significant push to strengthen programming around this through broad funding and programming streams. However, while gender inequality underpins IPV and HIV acquisition, in different contexts a variety of other factors intersect to shape this vulnerability. Using reflections focused on young women living in urban informal settlements and the Stepping Stones and Creating Futures intervention, this paper illustrates the need to understand the specific drivers of HIV and IPV in any given context and the need for interventions to prevent this. Any intervention needs to include three key components: 1) resonate with the lived realities of women they target; 2) tackle multiple factors shaping women's vulnerability to IPV and HIV simultaneously; and 3) consider how best to work with men and boys to achieve improved outcomes for women. Such an approach, it is argued, resonating with the "slow research" movement, will yield better outcomes for interventions, but will also require a fundamental rethinking of how interventions to prevent IPV and HIV amongst women are conceptualised, with a greater emphasis on understanding the ways in which gender resonates in each context and how interventions can operate. PMID- 27399042 TI - Resourcing resilience: social protection for HIV prevention amongst children and adolescents in Eastern and Southern Africa. AB - Adolescents are the only age group with growing AIDS-related morbidity and mortality in Eastern and Southern Africa, making HIV prevention research among this population an urgent priority. Structural deprivations are key drivers of adolescent HIV infection in this region. Biomedical interventions must be combined with behavioural and social interventions to alleviate the socio structural determinants of HIV infection. There is growing evidence that social protection has the potential to reduce the risk of HIV infection among children and adolescents. This research combined expert consultations with a rigorous review of academic and policy literature on the effectiveness of social protection for HIV prevention among children and adolescents, including prevention for those already HIV-positive. The study had three goals: (i) assess the evidence on the effectiveness of social protection for HIV prevention, (ii) consider key challenges to implementing social protection programmes that promote HIV prevention, and (iii) identify critical research gaps in social protection and HIV prevention, in Eastern and Southern Africa. Causal pathways of inequality, poverty, gender and HIV risk require flexible and responsive social protection mechanisms. Results confirmed that HIV-inclusive child-and adolescent sensitive social protection has the potential to interrupt risk pathways to HIV infection and foster resilience. In particular, empirical evidence (literature and expert feedback) detailed the effectiveness of combination social protection particularly cash/in-kind components combined with "care" and "capability" among children and adolescents. Social protection programmes should be dynamic and flexible, and consider age, gender, HIV-related stigma, and context, including cultural norms, which offer opportunities to improve programmatic coverage, reach and uptake. Effective HIV prevention also requires integrated social protection policies, developed through strong national government ownership and leadership. Future research should explore which combinations of social protection work for sub-groups of children and adolescents, particularly those living with HIV. PMID- 27399044 TI - Relationship dynamics and sexual risk behaviour of male partners of female sex workers in Kampala, Uganda. AB - Regular male partners of female sex workers (FSWs) represent an important population to reach with HIV-prevention interventions. This paper discusses the relationship dynamics and HIV/sexually transmitted infection risk behaviour of men involved with self-identified FSWs in Kampala. Between 2011 and 2014 we conducted repeat in-depth interviews with 42 male partners of FSWs attending a clinic for women at high risk of HIV-infection in Kampala. Men publicly struggled with the stigma of dating women who are considered to be engaged in a shamed profession, but privately saw meaning in these relationships. In coping with the stigma, some described the work of their partners in terms that distanced them from sex work, while others struggled to have the control that "being a man" demanded since they could not monitor all movements of their partners. Dealing with HIV disclosure was hard and seeking support was difficult for some of the men, leading to missed opportunities and guilt. Despite challenges, relationships with sex workers offered men some benefits such as access to much needed care and treatment. A few men also admitted to being motivated by material and financial benefits from sex workers who they perceived as being rich and this was one factor that helped them sustain the relationships. These findings offer insights into the complex relationship dynamics within high risk sexual partnerships. However, the findings suggest that effective interventions that are couple centred can be established to promote better health. PMID- 27399045 TI - Placing contraception at the centre of the HIV prevention agenda. AB - Over the past decade, the global response to the HIV epidemic has been unprecedented, and enormous progress has been made. Significant investment in the roll out of antiretroviral treatment (ART) and efforts to increase treatment coverage have greatly reduced the number of AIDS-related deaths worldwide. There are a growing number of promising innovations to expand the HIV prevention mix. However, the reach of these interventions is still very limited in adolescent girls and young women (15-24 years) and the full realisation of the intervention mandates has not yet been achieved. The HIV prevention field has been criticised for the tendency to adopt a narrow focus. The Fast-Track Strategy offers a unique opportunity for the HIV prevention field to broaden its gaze and to begin to identify synergies (and efficiencies) with prevention approaches from other global development priorities, namely sexual and reproductive health and rights (SRHR). This paper applies a SRHR lens to HIV prevention by highlighting the critical relationship between unintended pregnancy and HIV, and seeks to expand on earlier debates that prevention of HIV and prevention of unintended pregnancy are inextricably linked, complementary activities with interrelated and common goals. We call for the prioritisation of prevention of unintended pregnancy amongst two overlapping population groups - girls and young women (15-24 years old) and women living with HIV - as a key tactic to accomplish the Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track Strategy and as a way to fully realise existing HIV prevention efforts. We discuss the intersecting pathways between HIV prevention and unintended pregnancy prevention and build a case for contraception to be placed at the centre of the HIV prevention agenda. PMID- 27399046 TI - Funding of community-based interventions for HIV prevention. AB - Since the start of the HIV epidemic, community responses have been at the forefront of the response. Following the extraordinary expansion of global resources, the funding of community responses rose to reach at least US$690 million per year in the period 2005-2009. Since then, many civil society organisations (CSOs) have reported a drop in funding. Yet, the need for strong community responses is even more urgent, as shown by their role in reaching the Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track targets. In the case of antiretroviral treatment, interventions need to be adopted by most people at risk of HIV in order to have a substantial effect on the prevention of HIV at the population level. This paper reviews the published literature on community responses, funding and effectiveness. Additional funding is certainly needed to increase the coverage of community-based interventions (CBIs), but current evidence on their effectiveness is extremely mixed, which does not provide clear guidance to policy makers. This is especially an issue for adolescent girls and young women in Eastern and Southern Africa, who face extremely high infection risk, but the biomedical prevention tools that have been proven effective for the general population still remain pilot projects for this group. Research is especially needed to isolate the factors affecting the likelihood that interventions targeting this group are consistently successful. Such work could be focused on the community organisations that are currently involved in delivering gender-sensitive interventions. PMID- 27399047 TI - (Re)politicising and (re)positioning prevention: community mobilisations and AIDS prevention in the new AIDS era. AB - An increasing focus on the relationship between AIDS prevalence and socio economic inequality signals the need for a revaluation of the role of "politics" and "power" in AIDS prevention. This revaluation bears great significance when considering the future trajectories of the AIDS prevention efforts that target highly marginalised populations with high prevalence rates. An emphasis on intersecting forms of inequality has direct implications for the future of AIDS prevention practice. This study explores the experiences of participants, facilitators and local stakeholders applying the United Nations Development Programme (UNDP) Community Capacity Enhancement-Community Conversations (CCE-CC) approach to AIDS prevention in the Eastern Cape province of South Africa. It uses the political narrative analysis of life histories and semi-structured interviews as a means to interrogate the lived experiences of local actors participating in or influenced by this popularised form of community mobilisation used throughout sub-Saharan Africa. Findings suggest the need for a more explicit and intentional valuation for the intersection between the social and political determinants of health in programmes that use community mobilisation as prevention. They also signal a need to critically re-evaluate "community mobilisation" as an AIDS prevention tradition. Intersecting social and political power dynamics play a significant role in both opening up and constraining community mobilisation efforts. This paper proposes the need for a pedagogical turn to "deep organising" and "participatory forms of democracy", as a necessary frontier for programmes working with highly marginalised populations with high prevalence rates. Programmes need to more explicitly support, protect, and advocate for the ability of affected communities to engage in political processes, discourse and long-term organising. PMID- 27399048 TI - Traditional healers and the "Fast-Track" HIV response: is success possible without them? AB - The rapid scale-up of effective HIV prevention strategies is a central theme of the post-2015 health and development agenda. All major global HIV and AIDS funders have aligned their policies and plans to achieve sharp reductions in new HIV infections and reach epidemic control by 2030. In these "fast-track" plans, increased antiretroviral treatment coverage and the attainment of viral suppression are pivotal, and there is firm recognition of the need for countries to mobilise more domestic resources and build stronger community clinic systems. There is little in these bold plans, however, to suggest that the now 30-year-old call by the World Health Organization (WHO) and other organisations to establish systematic collaborations with the traditional health sector will finally be heeded. In the context of sub-Saharan Africa's HIV epidemic, a significant body of literature demonstrates the critical role that traditional healers can play in improving the success of health programmes, including those for HIV prevention. This paper provides a brief history of collaboration with traditional healers for HIV followed by a description of several successful collaborations and discussion of key elements for success. We argue that the traditional health sector is a major resource that has yet to be sufficiently mobilised against HIV. As we shift from a short-term HIV response to a longer-term and more sustainable response, there is an urgent need to accelerate efforts to leverage and partner with the hundreds of thousands of traditional health practitioners who are already providing health services in communities. Failure to better attune our work to the medical pluralism of communities affected by HIV will continue to hinder HIV programming success and help assure that ambitious post-2015 HIV prevention and control goals are not realised. PMID- 27399049 TI - Fast-tracking HIV prevention: scientific advances and implementation challenges. PMID- 27399052 TI - Intensive Psychotherapy for Persistent Dissociative Processes: The Fear of Feeling Real, by R. A. Chefetz. PMID- 27399050 TI - Synthesis of Kappa Opioid Antagonists Based On Pyrrolo[1,2-alpha]quinoxalinones Using an N-Arylation/Condensation/Oxidation Reaction Sequence. AB - The quinoxaline and quinoxalinone family of nitrogen heterocycles is present in molecules of therapeutic relevance for diverse applications ranging from infectious diseases to neuroscience targets. Here, we describe a general synthetic sequence to afford pyrrolo[1,2-alpha]quinoxalinones from commercially available starting materials and their use in preparing potential kappa opioid receptor antagonists. The biological data obtained from the latter set of compounds is briefly presented and discussed. PMID- 27399054 TI - Erratum. PMID- 27399053 TI - Effects of Autism Spectrum Disorder Insurance Mandates on the Treated Prevalence of Autism Spectrum Disorder. AB - IMPORTANCE: Most states have passed insurance mandates requiring commercial health plans to cover services for children with autism spectrum disorder (ASD). Insurers have expressed concerns that these mandates will increase the number of children diagnosed with ASD (treated prevalence) and therefore increase costs associated with their care. To our knowledge, no published studies have addressed this question. OBJECTIVE: To examine whether implementing ASD insurance mandates increases the number of commercially insured children diagnosed with ASD. DESIGN, SETTING, AND PARTICIPANTS: A difference-in-differences study was performed using inpatient and outpatient health insurance claims for children 21 years or younger covered by 3 of the largest insurers in the United States-United HealthCare, Aetna, and Humana-from January 1, 2008, through December 31, 2012, made available through the Health Care Cost Institute. Data analysis was conducted from March 15 to August 11, 2015. EXPOSURES: Implementation of an ASD insurance mandate in a child's state of residence. MAIN OUTCOMES AND MEASURES: The treated prevalence of ASD, measured as a binary indicator of whether a given child in a given calendar month had at least 1 health care service claim associated with a diagnosis of ASD. RESULTS: The adjusted treated prevalence among 1 046 850 eligible children (575 299 male [55.0%]) in states with ASD insurance mandates was 1.8 per 1000 and 1.6 per 1000 among children in states without such a mandate (P = .006). The mean increase in treated prevalence attributable to the mandates was 0.21 per 1000 children during the study period (95% CI, 0.11-0.30; P < .001). Mandates in place longer had a larger effect on treated prevalence. The mean increase in treated prevalence of ASD attributable to the mandate was 0.17 per 1000 children (95% CI, 0.09-0.24; P < .001) in the first year following implementation, 0.27 per 1000 children (95% CI, 0.13-0.42; P < .001) in the second year, and 0.29 per 1000 children (95% CI, 0.15-0.42; P < .001) 3 years or more following implementation. CONCLUSIONS AND RELEVANCE: Implementing state ASD insurance mandates resulted in increases in the number of children diagnosed with ASD; these numbers increased each year after implementation. Even 3 years or more after implementation, however, treated prevalence of ASD was much lower than community prevalence estimates. This finding may allay concerns that mandates will substantially increase insurance costs, but it suggests that many commercially insured children with ASD remain undiagnosed or are being treated only through publicly funded systems. PMID- 27399057 TI - All-Dielectric Silicon Nanogap Antennas To Enhance the Fluorescence of Single Molecules. AB - Plasmonic antennas have a profound impact on nanophotonics as they provide efficient means to manipulate light and enhance light-matter interactions at the nanoscale. However, the large absorption losses found in metals can severely limit the plasmonic applications in the visible spectral range. Here, we demonstrate the effectiveness of an alternative approach using all-dielectric nanoantennas based on silicon dimers to enhance the fluorescence detection of single molecules. The silicon antenna design is optimized to confine the near field intensity in the 20 nm nanogap and reach a 270-fold fluorescence enhancement in a nanoscale volume of lambda(3)/1800 with dielectric materials only. Our conclusions are assessed by combining polarization resolved optical spectroscopy of individual antennas, scanning electron microscopy, numerical simulations, fluorescence lifetime measurements, fluorescence burst analysis, and fluorescence correlation spectroscopy. This work demonstrates that all-silicon nanoantennas are a valid alternative to plasmonic devices for enhanced single molecule fluorescence sensing, with the additional key advantages of reduced nonradiative quenching, negligible heat generation, cost-efficiency, and complementary metal-oxide-semiconductor (CMOS) compatibility. PMID- 27399058 TI - Wernicke encephalopathy in a patient with liver failure: Clinical case report. AB - Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice.A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1.To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians' awareness of its possible onset. PMID- 27399059 TI - Economic evaluation study (CHEER-compliant): Cost-effectiveness analysis of RAS screening for treatment of metastatic colorectal cancer based on the CALGB 80405 trial. AB - Cetuximab (Cetux)/Bevacizumab (Bev) treatments have shown considerably survival benefits for patients with metastatic colorectal cancer (mCRC) in the last decade. But they are costly. Currently, no data is available on the health economic implications of testing for extended RAS wild-type (wt) prior to Cetux/Bev treatments of patients with mCRC. This paper aimed to evaluate the cost effectiveness of predictive testing for extended RAS-wt status in mCRC in the context of targeting the use of Cetux/Bev.Markov model 1 was conducted to provide evidence evaluating the cost-effectiveness of predictive testing for KRAS-wt or extended RAS-wt status based on treatments of chemotherapy plus Cetux/Bev. Markov model 2 assessed the cost-effectiveness of FOLFOX plus Cetux/Bev or FOLFIRI plus Cetux/Bev in extended RAS-wt population. Primary base case data were identified from the CALGB 80405 trial and the literatures. Costs were estimated from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated.In analysis 1, the cost per QALY was $88,394.09 for KRAS Cetux, $80,797.82 for KRAS-Bev, $82,590.72 for RAS-Cetux, and $75,358.42 for RAS Bev. The ICER for RAS-Cetux versus RAS-Bev was $420,700.50 per QALY gained. In analysis 2, the cost per QALY was $81,572.61, $80,856.50, $80,592.22, and $66,794.96 for FOLFOX-Cetux, FOLFOX-Bev, FOLFIRI-Cetux, and FOLFIRI-Bev, respectively. The analyses showed that the extended RAS-wt testing was less costly and more effective versus KRAS-wt testing before chemotherapy plus Cetux/Bev. Furthermore, FOLFIRI plus Bev was the most cost-effective strategy compared with others in extended RAS-wt population.It was economically favorable to identify patients with extended RAS-wt status. Furthermore, FOLFIRI plus Bev was the preferred strategy in extended RAS-wt patients. PMID- 27399060 TI - Oral contraception following abortion: A systematic review and meta-analysis. AB - Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs postabortion. We conducted this systematic review and meta-analysis in the present study reported immediate administration of OCs or combined OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies.A total of 8 major authorized Chinese and English databases were screened from January 1960 to November 2014. Randomized controlled trials in which patients had undergone medical or surgical abortions were included. Chinese studies that met the inclusion criteria were divided into 3 groups: administration of OC postmedical abortion (group I; n = 1712), administration of OC postsurgical abortion (group II; n = 8788), and administration of OC in combination with traditional Chinese medicine postsurgical abortion (group III; n = 19,707).In total, 119 of 6160 publications were included in this analysis. Significant difference was observed in group I for vaginal bleeding time (P = 0.0001), the amount of vaginal bleeding (P = 0.03), and menstruation recovery period (P < 0.00001) compared with the control groups. Group II demonstrated a significant difference in vaginal bleeding time (P < 0.00001), the amount of vaginal bleeding (P = 0.0002), menstruation recovery period (P < 0.00001), and endometrial thickness at 2 (P = 0.003) and 3 (P < 0.00001) weeks postabortion compared with the control group. Similarly, a significant difference was observed in group III for reducing vaginal bleeding time (P < 0.00001) and the amount of vaginal bleeding (P < 0.00001), shortening the menstruation recovery period (P < 0.00001), and increasing endometrial thickness 2 and 3 weeks after surgical abortion (P < 0.00001, all).Immediate administration of OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies. PMID- 27399061 TI - Racial/ethnic disparities in annual mammogram compliance among households in Little Haiti, Miami-Dade County, Florida: An observational study. AB - INTRODUCTION: Breast cancer is the most commonly diagnosed cancer and the 2nd leading cause of cancer-related deaths among women in the U.S. Although routine screening via mammogram has been shown to increase survival through early detection and treatment of breast cancer, only 3 out of 5 women age >=40 are compliant with annual mammogram within the U.S. and the state of Florida. A breadth of literature exists on racial/ethnic disparities in compliance with mammogram; however, few such studies include data on individual Black subgroups, such as Haitians. This study assessed the association between race/ethnicity and annual mammogram compliance among randomly selected households residing in the largely Haitian community of Little Haiti, Miami-Dade County (MDC), Florida. METHODS: This study used cross-sectional, health data from a random-sample, population-based survey conducted within households residing in Little Haiti between November 2011 and December 2012 (n = 951). Mammogram compliance was defined as completion of mammogram by all female household members within the 12 months prior to the survey. The association between mammogram compliance and race/ethnicity was assessed using binary logistic regression models. Potential confounders were identified as factors that were conservatively associated with both compliance and race/ethnicity (P <= 0.20). Analyses were restricted to households containing at least 1 female member age >=40 (n = 697). RESULTS: Overall compliance with annual mammogram was 62%. Race/ethnicity was significantly associated with mammogram compliance (P = 0.030). Compliance was highest among non-Hispanic Black (NHB) households (75%), followed by Hispanic (62%), Haitian (59%), and non-Hispanic White (NHW) households (51%). After controlling for educational level, marital status, employment status, the presence of young children within the household, health insurance status, and regular doctor visits, a borderline significant disparity in mammogram compliance was observed between Haitian and NHB households (adjusted odds ratio = 1.63, P = 0.11). No other racial/ethnic disparities were observed. DISCUSSION: Compliance with annual mammogram was low among the surveyed households in Little Haiti. Haitian households underutilized screening by means of annual mammogram compared with NHB households, although this disparity was not significant. Compliance rates could be enhanced by conducting individualized, mammogram screening-based studies to identify the reasons behind low rate of compliance among households in this underserved, minority population. PMID- 27399062 TI - A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer. AB - Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78 1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26-1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix. PMID- 27399063 TI - Public opinions on disclosure of tobacco components: Results of a nationwide cross-sectional survey in Republic of Korea. AB - This study aimed to explore public views on disclosure of tobacco components in an effort to develop a comprehensive regulatory system facilitating implementation of the Framework Convention on Tobacco Control (FCTC) Articles 9 and 10 in Korea.In all, 1200 representative Koreans 19 years old or older were enrolled and information on their general characteristics, smoking status, awareness of the effects of smoking on health, and views on the public disclosure of tobacco components was collected by telephone using a structured questionnaire. Factors associated with acceptance of the need for public disclosure of tobacco components were identified via multivariate analysis.Most participants considered it necessary to publicly disclose tobacco components (95.9%) and were aware of the risk to health posed by smoking (76.0%). The prevalent view was that tobacco companies should be legally required to publicly disclose details of the components of cigarettes, their levels per cigarette, and their effects on health. The most effective means of disclosure were considered to be the mass media, printed materials, and labels on cigarette packs. Females and never-smokers (odds ratio [OR]: 4.39, 95% confidence interval [95% CI]: 1.76 10.94) more readily accepted the need for public disclosure, whereas those of lower educational level and/or who were less aware of the harm to health posed by smoking (OR: 0.05, 95% CI: 0.01-0.18) were less likely to be accepting.The attitude of the general population ensures that FCTC Articles 9 and 10 will be successfully implemented in Korea. Further public consultation on the details of disclosure would be useful for the development of a comprehensive regulatory system. PMID- 27399064 TI - Respiratory diseases and the impact of cough in Taiwan: Results from the APBORD observational study. AB - Chronic respiratory diseases such as asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming increasingly prevalent in the Asia-Pacific region. The Asia-Pacific Burden of Respiratory Diseases (APBORD) study was a cross-sectional, observational study which examined the disease and economic burden of AR, asthma, COPD, and rhinosinusitis across Asia-Pacific using 1 standard protocol. Here we report symptoms, healthcare resource use (HCRU), work impairment, and associated cost in Taiwan.Consecutive participants aged >= 18 years presenting to a physician with symptoms meeting the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Participants and their treating physician completed surveys detailing respiratory symptoms, HCRU, work productivity, and activity impairment. Costs including direct medical costs and indirect costs associated with lost work productivity were calculated.The study enrolled 1001 patients. AR was the most frequent primary diagnosis (31.2%). A quarter of patients presented with a combination of respiratory diseases, with AR and asthma being the most frequent combination (14.1%). Cough or coughing up phlegm was the primary reason for the medical visit for patients with asthma and COPD, whereas nasal symptoms (watery runny nose, blocked nose, and congestion) were the primary reasons for AR and rhinosinusitis. Specialists were the most frequently used healthcare resource by patients with AR (26.1%), asthma (26.4%), COPD (26.6%), and rhinosinusitis (47.3%). The mean annual cost per patient with a respiratory disease was US$4511 (SD 5395). The cost was almost double for employed patients (US$8047, SD 6175), with the majority attributable to lost productivity.Respiratory diseases have a significant impact on disease burden in Taiwan. Treatment strategies that prevent lost work productivity could greatly reduce the economic burden of these diseases. PMID- 27399065 TI - Vitamin D serum level is associated with Child-Pugh score and metabolic enzyme imbalances, but not viral load in chronic hepatitis B patients. AB - Vitamin D deficiency is common in patients with chronic liver diseases. However, vitamin D status in persons with chronic hepatitis B virus (HBV) infection is not consistently reported. Specifically, the impact of liver dysfunction on vitamin D status has not been well addressed.We recruited a group of patients (n = 345) with chronic hepatitis B (n = 115), hepatitis B related cirrhosis (n = 115), and age- and gender-matched healthy controls (n = 115). Serum 25-hydroxyvitamin D3 [25(OH)D3], its related metabolic enzymes, intact parathyroid hormone were measured. Calcium, magnesium, and phosphorus were obtained from medical record.Serum 25(OH)D3 levels in chronic hepatitis B patients (7.83 +/- 3.47 ng/mL) were significantly lower than that in healthy controls (9.76 +/- 4.36 ng/mL, P < 0.001), but significantly higher than that in hepatitis B-related cirrhotic patients (5.21 +/- 3.67 ng/mL, P < 0.001). Furthermore, 25(OH)D3 decreased stepwise with higher Child-Pugh classification. However, there were no significant differences in 25(OH)D3 levels between (1) hepatitis B e antigen (HBeAg +) and HBeAg(-) persons, or (2) among persons with different HBV viral load, or (3) between treatment naive and patients on antiviral therapy. Multiple logistic regression analyses confirmed that higher Child-Pugh score was independently associated with 25(OH)D3 deficiency (<10 ng/mL) with an odds ratio of 1.20 (confidence interval 1.03-1.39, P = 0.016). Levels of cytochrome P450 (CYP) 27A1 were significantly decreased, whereas levels of CYP24A1 were significantly elevated in cirrhotic patients.These results suggest that decreasing vitamin D levels are likely to be a result, rather than a cause, of liver dysfunction and irrespective of HBV viral load. Reduction in 25(OH)D3 levels is possibly due to downregulation of the synthetic hydroxylase CYP27A1 and concurrent upregulation of degrading CYP24A1 in patients with liver cirrhosis. PMID- 27399066 TI - Risk factors for renal impairment revealed after unilateral adrenalectomy in patients with primary aldosteronism. AB - Primary aldosteronism (PA) may induce significant decline of renal function and structural damage of kidney. However, it is difficult to evaluate accurate renal function in patients with PA, because glomerular hyperfiltration and aldosterone escape can conceal renal impairment. In this retrospective cohort study, we compared changes in renal function after unilateral adrenalectomy between patients with PA and patients with other adrenal diseases. Risk factors associated with postoperative renal impairment in patients with PA were analyzed.A total of 558 patients who received unilateral adrenalectomy between January 2002 and June 2013 were included: 136 patients with PA and 422 patients with other adrenal diseases (control). Postoperative serial changes in estimated glomerular filtration rate (eGFR) were analyzed in both groups. Multivariate analyses were performed to identify risk factors of renal impairment after adrenalectomy in all patients and the PA group. Postoperative renal impairment was defined as postoperative eGFR decline of >25% from preoperative eGFR. Chronic kidney disease (CKD) was defined as an eGFR <60 mL/min/1.73 m.There were no differences in preoperative eGFR between groups. The PA group showed a significant decrease in eGFR 3 days, 2 weeks, and 6 months after surgery compared to the control group. The PA group showed significant improvement of hypertension after surgery. In the PA group, 53 (39.0%) patients showed postoperative renal impairment. Multivariate regression analysis identified long-standing hypertension, low body mass index, low serum potassium, and high preoperative eGFR as risk factors for postoperative renal impairment. Among the 89 patients with preoperative eGFR >=60 mL/min/1.73 m, 29 (32.6%) patients developed CKD postoperatively. Age, low serum potassium, low preoperative eGFR, and high serum cholesterol or uric acid were associated with the postoperative CKD development.Our study demonstrates that patients with PA with old age, low serum potassium, long-standing hypertension, and high serum uric acid or cholesterol are at risk of renal impairment after surgical treatment. High preoperative eGFR was also a risk factor for postoperative renal impairment, whereas low preoperative eGFR was a risk factor for postoperative CKD. Close monitoring of renal function and adequate management are required for patients with these risk factors. PMID- 27399067 TI - Local recurrence after curative resection for rectal carcinoma: The role of surgical resection. AB - Local recurrence of rectal cancer is difficult to treat, may cause severe and disabling symptoms, and usually has a fatal outcome. The aim of this study was to document the clinical nature of locally recurrent rectal cancer and to determine the effect of surgical resection on long-term survival.A retrospective review was conducted of the prospectively collected medical records of 2485 patients with primary rectal adenocarcinoma who underwent radical resection between September 1994 and December 2008.In total, 147 (5.9%) patients exhibited local recurrence. The most common type of local recurrence was lateral recurrence, whereas anastomotic recurrence was the most common type in patients without preoperative concurrent chemoradiotherapy (CCRT). Tumor location with respect to the anal verge significantly affected the local recurrence rate (P < 0.001), whereas preoperative CCRT did not affect the local recurrence rate (P = 0.433). Predictive factors for surgical resection of recurrent rectal cancer included less advanced tumor stage (P = 0.017, RR = 3.840, 95% CI = 1.271-11.597), axial recurrence (P < 0.001, RR = 5.772, 95% CI = 2.281-14.609), and isolated local recurrence (P = 0.006, RR = 8.679, 95% CI = 1.846-40.815). Overall survival after diagnosis of local recurrence was negatively influenced by advanced pathologic tumor stage (P = 0.040, RR = 1.867, 95% CI = 1.028-3.389), positive CRM (P = 0.001, RR = 12.939, 95% CI = 2.906-57.604), combined distant metastases (P = 0.001, RR = 2.086, 95% CI = 1.352-3.218), and nonsurgical resection of recurrent tumor (P < 0.001, RR = 4.865, 95% CI = 2.586-9.153).In conclusion, the clinical outcomes of local recurrence after curative resection of rectal cancer are diverse. Surgical resection of locally recurrent rectal cancer should be considered as an initial treatment, especially in patients with less advanced tumors and axial recurrence. PMID- 27399068 TI - Clinical effects of lateral wedge arch support insoles in knee osteoarthritis: A prospective double-blind randomized study. AB - We compared the short-term efficacy of rigid versus soft lateral wedge arch support (LWAS) insoles for patients with knee osteoarthritis (OA), as assessed using the International Classification of Functioning, Disability and Health (ICF) system, through a prospective, double-blind, randomized controlled trial.Participants who fulfilled the combined radiographic and clinical criteria for knee OA, as defined by the American College of Rheumatology, were randomly prescribed 1 pair of rigid or soft LWAS insoles. Body functions and structures were evaluated according to Kellgren-Lawrence scores, the Foot Posture Index, Hospital Anxiety and Depression Scale scores, the pain-pressure threshold, postural stability, dynamic balance, and fall risk; activities and participation were assessed according to 10-m fast speed walking, stair climbing and chair rising times, and Chronic Pain Grade questionnaire responses; and knee OA-related health status was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Hospital Anxiety and Depression Scale scores, the pain-pressure threshold, physical activity, balance, Chronic Pain Grade questionnaire responses, and the KOOS were recorded before treatment and at 1-, 2-, and 3-month follow-ups.We enrolled 90 participants, 70 women and 20 men, with mean ages of 60.6 +/- 10.8 and 63.1 +/- 10.8 years in the rigid and soft LWAS insole groups, respectively. Repeated-measures analysis of covariance revealed significant time * group effect improvements in pain (P = 0.008 for the KOOS), stair ascent time (P = 0.003), daily living function (P = 0.003 for the KOOS), sports and recreation function (P = 0.012 for the KOOS), and quality of life (P = 0.021 for the KOOS) in the soft LWAS insole group.Patients with knee OA who used soft LWAS insoles for a short term showed more significant improvement than did those who used rigid LWAS insoles in pain, physical activity, daily living function, sports and recreation function, and quality of life, which belong to the body functions and structures and the activities and participation components in the ICF scheme. PMID- 27399070 TI - Early postoperative complications have long-term impact on quality of life after restorative proctocolectomy. AB - INTRODUCTION: Early postoperative complications graded according to the Clavien Dindo classification system have not previously been correlated with long-term quality of life outcomes in patients who have had restorative proctocolectomy with ileal pouch-anal anastomosis. This study aimed to assess the severity of early postoperative complications and compared these in terms of the long-term quality of life after restorative proctocolectomy in a population-based cohort of patients (operated on from 1984 to 2013). It was hypothesized that those who experienced grade 3 or 4 Clavien-Dindo complications would have worse quality of life at follow-up. METHODS: This population-based study used a combination of a retrospective note review and a cross-sectional questionnaire. All patients with a restorative proctocolectomy performed in 1984-2013 in the Canterbury region were recruited using multiple sources. Early (<=30 days) and late (>30 days) complication rates were obtained via patient records. Early postoperative complications were graded according to the Clavien-Dindo classification. Quality of life was measured using the inflammatory bowel disease questionnaire. RESULTS: One hundred and thirty-six people were identified with a median follow-up of 12 years. Data were available for 121 patients for early complications and 112 for late complications. Eighty-one eligible participants had their quality of life assessed (86% response rate). Early complications occurred in 26% and 76% had late complications. Those who had Clavien-Dindo grade 3 or 4 early complications had lower quality of life scores (P = 0.001) as did females (P = 0.004) and those with a stricture (P = 0.031). CONCLUSION: This population-based study with long term follow-up demonstrates that Clavien-Dindo grade 3 and 4 postoperative complications are important in determining quality of life in the long term. The reduction in these complications should be a focus of patient management, as it should improve long-term quality of life. PMID- 27399069 TI - The feasibility of CT lung volume as a surrogate marker of donor-recipient size matching in lung transplantation. AB - Donor-recipient size matching in lung transplantation (LTx) by computed tomography lung volume (CTvol) may be a reasonable approach because size matching is an anatomical issue. The purpose of this study is to evaluate the feasibility of CTvol as a surrogate marker of size matching in LTx by comparing CTvol and predicted total lung capacity (pTLC) to reference total lung capacity (TLC) values.From January to December 2014, data from 400 patients who underwent plethysmography, pulmonary function testing (PFT), and chest computed tomography scans were reviewed retrospectively. Enrolled 264 patients were divided into 3 groups according to PFT results: Group I, obstructive pattern; Group II, restrictive pattern; Group III, normal range. The correlations between pTLC and TLC and between CTvol and TLC were analyzed, and the linear correlation coefficients were compared. The percentage error rates of pTLC and CTvol were calculated and absolute error rates were compared.The correlation coefficient between CTvol and TLC in Group I was larger than that of pTLC and TLC (0.701 vs 0.432, P = 0.002). The absolute percentage error rate between CTvol and pTLC was lower than that of pTLC in Group II (15.3% +/- 11.9% vs 42.2% +/- 28.1%, P < 0.001).CTvol showed similar or better correlation with TLC compared to the pTLC in normal participants and patients with obstructive or restrictive pulmonary diseases. CTvol showed a smaller error rate in patients with restrictive disease. The results suggest that CTvol may be a feasible method for size matching in LTx. PMID- 27399071 TI - Outcomes and factors associated with survival of patients with HIV/AIDS initiating antiretroviral treatment in Liangshan Prefecture, southwest of China: A retrospective cohort study from 2005 to 2013. AB - Human immunodeficiency virus (HIV)-positive cases have been reported among people who injected drugs in Liangshan Prefecture in southwest of China since 1995 and Liangshan has become one of the most seriously affected epidemic areas in China. In 2004, several patients with HIV/acquired immunodeficiency syndrome (AIDS) initiated antiretroviral treatment (ART) at the Central Hospital of Liangshan Prefecture. From 2005 to 2013, the number of patients receiving ART dramatically increased.We conducted a retrospective cohort study to analyze the long-term survival time and associated factors among patients with HIV/AIDS who received ART in Liangshan Prefecture for the first time. Data were collected from the Chinese AIDS Antiretroviral Therapy DATAFax Information System. A life table and the Kaplan-Meier and Cox proportion hazard regression were used to calculate the survival time and its associated factors, respectively.Among 8310 ART-naive patients with HIV/AIDS who initiated ART, 436 patients died of AIDS-related diseases, and their median time of receiving ART was 15.0 +/- 12.3 months, whereas 28.7% of them died within the first 6 months after treatment. The cumulative survival rates of those receiving ART in 1, 2, 3, 4, and 5 years were 97.1%, 93.4%, 90.6%, 88.8%, and 86.0%, respectively. Multivariate Cox regression analysis showed that male patients on ART were at a higher risk of death from AIDS-related diseases (adjusted hazard ratio [AHR] = 1.5, 95% confidence interval [CI]: 1.1-2.1) than female patients. Patients infected with HIV through injection drug use (IDU) were at a higher risk of death (AHR = 1.6, 95% CI: 1.2-2.2) than those infected through heterosexual transmission. Patients with a baseline CD4 cell count <50/mm (AHR = 9.8, 95% CI: 6.0-15.9), 50-199/mm (AHR = 3.3, 95% CI: 2.3-4.6), and 200-349/mm (AHR = 1.7, 95% CI: 1.2-2.3) were at a higher risk of death than those with a CD4 cell count >=350/mm.ART prolonged survival time of patients with HIV/AIDS and improved their survival probability. Patients with HIV/AIDS should be consistently followed up and the CD4 T-cell count regularly monitored, and timely and early antiretroviral therapy initiated in order to achieve a better survival rate. PMID- 27399072 TI - Effects of intraoperative inhaled iloprost on primary graft dysfunction after lung transplantation: A retrospective single center study. AB - DESIGN: Inhaled iloprost was known to alleviate ischemic-reperfusion lung injury. We investigated whether intraoperative inhaled iloprost can prevent the development of primary graft dysfunction after lung transplantation. Data for a consecutive series of patients who underwent lung transplantation with extracorporeal membrane oxygenation were retrieved. By propensity score matching, 2 comparable groups of 30 patients were obtained: patients who inhaled iloprost immediately after reperfusion of the grafted lung (ILO group); patients who did not receive iloprost (non-ILO group). RESULTS: The severity of pulmonary infiltration on postoperative days (PODs) 1 to 3 was significantly lower in the ILO group compared to the non-ILO group. The PaO2/FiO2 ratio was significantly higher in the ILO group compared to the non-ILO group (318.2 +/- 74.2 vs 275.9 +/ 65.3 mm Hg, P = 0.022 on POD 1; 351.4 +/- 58.2 vs 295.8 +/- 53.7 mm Hg, P = 0.017 on POD 2; and 378.8 +/- 51.9 vs 320.2 +/- 66.2 mm Hg, P = 0.013 on POD 3, respectively). The prevalence of the primary graft dysfunction grade 3 was lower in the ILO group compared to the non-ILO group (P = 0.042 on POD 1; P = 0.026 on POD 2; P = 0.024 on POD 3, respectively). The duration of ventilator use and intensive care unit were significantly reduced in the ILO group (P = 0.041 and 0.038). CONCLUSIONS: Intraoperative inhaled iloprost could prevent primary graft dysfunction and preserve allograft function, thus reducing the length of ventilator care and intensive care unit stay, and improving the overall early post-transplant morbidity in patients undergoing lung transplantation. PMID- 27399073 TI - Long-term clinical outcomes of laparoscopy-assisted distal gastrectomy versus open distal gastrectomy for early gastric cancer: A comprehensive systematic review and meta-analysis of randomized control trials. AB - The objective of this study was to compare long-term surgical outcomes and complications of laparoscopy-assisted distal gastrectomy (LADG) with open distal gastrectomy (ODG) for the treatment of early gastric cancer (EGC) based on a review of available randomized controlled trials (RCTs) evaluated using the Cochrane methodology.RCTs comparing LADG and ODG were identified by a systematic literature search in PubMed, Cochrane Library, MEDLINE, EMBASE, Scopus, and the China Knowledge Resource Integrated Database, for papers published from January 1, 2003 to July 30, 2015. Meta-analyses were performed to compare the long-term clinical outcomes.Our systematic literature search identified 8 eligible RCTs including 732 patients (374 LADGs and 358 ODGs), with low overall risk of bias. Long-term mortality and relapse rate were comparable for both techniques. The long-term complication rate was 8.47% in LADG groups and 13.62% in the ODG group, indicating that LADG was associated with lower risk for long-term complications (RR = 0.63; 95%CI = 0.39-1.00; P = 0.03).In the treatment of EGC, LADG lowered the rate of long- and short-term complications and promoted earlier recovery, with comparable oncological outcomes to ODG. PMID- 27399074 TI - Duodenal perforation and esophageal ischemia following transarterial chemoembolization for hepatocellular carcinoma: A case report. AB - Transarterial chemoembolization (TACE) is frequently used for treatment of unresectable hepatocellular carcinoma (HCC) and can also be used for case of liver metastases from rectal cancer. Although it is recognized as safe and effective treatment, various complications have been reported. However, post-TACE duodenal perforation with duodenal and esophageal ischemia has not been reported in the literature. A 43-year-old male had experienced duodenal perforation combined with duodenal and lower esophageal ischemia after 8 times of repeated TACE for recurrent and unresectable HCCs, that was confirmed on esophagogastroduodenoscopy and abdominal computed tomography. Interestingly, operative findings showed complete recovery of duodenal ischemia except perforation, and he recovered with just the segmental duodenectomy and gastrojejunostomy. We report a case of duodenal perforation with necrosis and esophageal ischemia after 8th TACE for unresectable HCC. Although this complication is rare and unexpected, it may result in severe sequelae requiring surgical repair.The careful procedure during TACE followed by post-TACE careful monitoring is required in patients with posthepatectomy or repeated TACE, especially in the case with unusual clinical manifestations. PMID- 27399075 TI - Presence of diabetic microvascular complications does not incrementally increase risk of ischemic stroke in diabetic patients with atrial fibrillation: A nationwide cohort study. AB - Conventional stroke risk prediction tools used in atrial fibrillation (AF) incorporate the presence of diabetes mellitus (DM) as a risk factor. However, it is unknown whether this risk is homogenous or dependent on the presence of diabetic microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy. The present study examined the risk of ischemic stroke in diabetic patients with and without microvascular complications. The present study used the National Health Insurance Research Database in Taiwan with detailed healthcare data on all-comers to the Taiwanese medical system from January 1, 1996 to December 31, 2011. AF and DM were identified when listed as discharge diagnoses or confirmed more than twice in the outpatient department. Patients on antithrombotic agents were excluded. The clinical endpoint was ischemic stroke. Among the 50,180 AF patients with DM, the majority had no microvascular complications (72.7%), while 2.6% had diabetic retinopathy, 8.4% had diabetic nephropathy, and 16.1% had diabetic neuropathy. Ischemic stroke occurred in 6003 patients, with a 4.74% annual risk of ischemic stroke. When compared with DM patients without microvascular complications, those with diabetic retinopathy, nephropathy, or neuropathy had higher incidences of ischemic stroke (4.65 vs 5.07, 4.77, or 5.20 per 100 person-years, respectively). However, after adjusting for confounding factors, the differences were no longer significant. In a large nationwide AF cohort with DM, risk of ischemic stroke was similar between patients with and without microvascular complications, suggesting that risk stratification of these patients does not require inclusion of diabetic retinopathy, nephropathy, and neuropathy. PMID- 27399076 TI - Mortality following snake bite envenomation by Bitis arietans in an HIV positive child: A case report. AB - Snake bites occur commonly in the rural areas of South Africa. Hospitals where snake bites are uncommon should always have protocols on standby in the event of such cases presenting. This is the first reported case documenting the effect of human immunodeficiency virus (HIV) on snake bite in South African children.A case report and review of relevant information about the case was undertaken.We present a case of a 1-year-old child referred from a peripheral hospital following a snake bite to the left upper limb with a compartment syndrome and features of cytotoxic envenomation. The patient presented late with a wide area of necrotic skin on the arm requiring extensive debridement. The underlying muscle was not necrotic. Polyvalent antivenom (South African Institute of Medical Research Polyvalent Snakebite Antiserum) administration was delayed by 4 days after the snake bite. The patient was also diagnosed with HIV and a persistent thrombocytopenia possibly due to both HIV infection and the snake bite venom. Lower respiratory tract infections with subsequent overwhelming sepsis ultimately resulted in the child's death.The case highlights the challenge of treating a snake bite in a young child with HIV and the detrimental outcome of delayed treatment. A protocol is essential in the management of snake bites in all hospitals.Level IV, Case report.This case highlights the interaction of snake bite envenomation and HIV infection on thrombocytopenia. PMID- 27399077 TI - Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding. AB - Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio >= 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland. PMID- 27399078 TI - Predictors of chronic kidney disease in type 2 diabetes: A longitudinal study from the AMD Annals initiative. AB - The identification of clinical predictors for the development of chronic kidney disease is a critical issue in the management of patients with type 2 diabetes mellitus.We evaluated 27,029 patients with type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) >=60 mL/min/1.73 m and normoalbuminuria from the database of the Italian Association of Clinical Diabetologists network. Primary outcomes were eGFR <60 mL/min/1.73 m and normoalbuminuria; albuminuria and eGFR >=60 mL/min/1.73 m; and eGFR <60 mL/min/1.73 m and albuminuria. Secondary outcomes were eGFR <60 mL/min/1.73 m and albuminuria. MEASUREMENTS: eGFR from serum creatinine by chronic kidney disease epidemiology collaboration equation (CKD-EPI), urinary albumin excretion, HbA1c, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), blood pressure, and body mass index.Over a 4-year period, 33.2% of patients (n = 8973) developed chronic kidney disease, 10.3% (n = 2788) showed a decline in eGFR <60 mL/min/1.73 m, 18.4% (n = 4978) developed albuminuria, and 4.5% (n = 1207) developed both features. Relative risk ratios (RRRs) for age (1.37, P < 0.001 by 5 years), sex (0.77, P < 0.001 for being male), body mass index (1.03, P < 0.001 by 1 kg/m), triglycerides (1.02, P < 0.001 by 10 mg/dL), and LDL-c (0.97, P = 0.004 by 10 mg/dL) were independently related to the onset of eGFR reduction. Age (1.08, P < 0.001 by 5 years), sex (1.36, P < 0.001 for being male), body mass index (1.02, P < 0.001 by 1 kg/m), triglycerides (1.01, P = 0.02 by 10 mg/dL), HDL-c, and LDL-c (0.97, P = 0.008 and 0.99, P = 0.003 by 5 and 10 mg/dL, respectively) were related to the onset of albuminuria. HbA1c and the intensity of antihypertensive treatment showed a weaker association with renal outcome.Reduction in eGFR and albuminuria showed distinct sets of risk factors, suggesting that different mechanisms are involved in the development of these 2 components of diabetic kidney disease. PMID- 27399080 TI - Leiomyosarcoma in the mandible: A rare case report. AB - Leiomyosarcoma (LMS) is a malignancy which very rarely occurs in maxillofacial location, and the course of the disease is not very characteristic.In this case report, we present a 58-year-old female patient with a painless tumor of the left angle of the mandible causing slight asymmetry of the face. She also reported that she observed deterioration in fitting of the lower denture in the oral cavity for several months, which she had used successfully for 5 years.On the basis of clinical tests, histopatological examination, and imaging (CT, MRI, ultrasound, pantomography), the patient was diagnosed with primary malignant leiomyosarcoma (LMS) of the mandibular corpus and ramus on the left side. The patient received combined surgical and oncological treatment. The first stage was a surgery, and then adjuvant radiotherapy was applied on the site of the resected tumor-a total dose of 60 Gy in 35 fractions. The patient's postoperative course was uneventful. She also underwent adjuvant therapy well. In the period of 3-year follow-up, no signs of recurrence were observed.The findings may extend our knowledge and experiences in the treatment of leiomvosarcoma in the craniofacial area. PMID- 27399079 TI - Factors associated with metabolically healthy status in obesity, overweight, and normal weight at baseline of ELSA-Brasil. AB - The primary aim of this study was to evaluate metabolically healthy status (MHS) among participants in obesity, overweight, and normal weight groups and characteristics associated with this phenotype using baseline data of Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The secondary aim was to investigate agreement among 4 different MHS criteria. This cross-sectional study included 14,545 participants aged 35 to 74 years with a small majority (54.1%) being women. Of all participants, 22.7% (n = 3298) were obese, 40.8% (n = 5934) were overweight, and 37.5% (n = 5313) were of normal weight.Socio-demographic, behavioral, and anthropometric factors related to MHS were ascertained. Logistic regression models estimated the odds of associations. We used 4 different criteria separately and in combination to define MHS: the National Health and Nutrition Examination Survey (NHANES), the National Cholesterol Education Program (NCEP-ATPIII), the International Diabetes Federation (IDF) and comorbidities, and the agreement between them were evaluated by Cohen-kappa coefficient.MHS was present among 12.0% (n = 396) of obese, 25.5% (n = 1514) of overweight, and 48.6% (n = 2582) of normal weight participants according to the combination of the 4 criteria. The agreement between all the 4 MHS criteria was strong (kappa 0.73 P < 0.001). In final logistic models, MHS was associated with lower age, female sex, lower body mass index (BMI), and weight change from age 20 within all BMI categories.This study showed that, despite differences in prevalence among the 4 criteria, MHS was associated with common characteristics at every BMI category. PMID- 27399081 TI - Preventative care for patients with inflammatory bowel disease in the Veterans Health Administration. AB - Patients with inflammatory bowel disease (IBD) have underlying immune dysregulation. Immunosuppressive medications put them at risk of infection. This study assessed rates of recommended vaccinations and preventative screening in patients with IBD.Nationwide data on patients diagnosed with IBD in the Veterans Health Administration (VHA) October 2004 to September 2014 were extracted. Variation in vaccination, screenings, and risk of death by demographic factors (age group, gender) were estimated in bivariate and multivariable analyses.During the 10-year study period, 62,002 patients were treated for IBD. Nonmelanoma skin cancer was found in 2.6%, and these patients more commonly accessed dermatology clinic (22.5% vs 15.2%; chi-square = 66.6; df = 1; P < 0.0001). In total, 15% received DEXA scans, especially women (34.7% vs 13.2% men; chi-square = 1415.5; df = 1; P < 0.0001). Eye manifestations were noted in 38.3% yet only 31% were referred to ophthalmology. Abnormal Pap smears were found for 15% of women <65 (compared to 5% among normal patient populations); 34% had no record of Pap smear in VHA data. Vaccination rates were modest: pneumococcal 39%; TDAP 23%; hepatitis B 3%; varicella and PPD <0.5%. In an adjusted logistic regression model, 5-year mortality was lower among those using primary care prior to IBD diagnosis (odds ratio [OR] = 0.61; 95% CI 0.55-0.68).Despite the current IBD guidelines, vaccination and preventative screening rates were unacceptably low among patients diagnosed with IBD. Interventions such as education and increased awareness may be needed to improve these rates. PMID- 27399082 TI - Trends of antidiabetic drug use in adult type 2 diabetes in Korea in 2002-2013: Nationwide population-based cohort study. AB - This study investigated trends in the prescription of antidiabetic medications for patients with type 2 diabetes, focusing on changing patterns of prescriptions and the cost of drugs during the last 10 years. Retrospective data on patients with type 2 diabetes aged 30 years or older were analyzed using information from the National Health Information Database collected by the National Health Insurance Service in Korea from January 2002 to December 2013. We identified patients with type 2 diabetes who had at least one service claim in each year during the study period. The prescribing information was collected and fixed-dose combination tablets were counted as each of their constituent classes. The total number of adults with type 2 diabetes who were treated using antidiabetic agents increased from 0.87 million in 2002 to 2.72 million in 2013 in Korea. Among antidiabetic medications in 2002, sulfonylurea (SU) was the most commonly used agent (87.2%), and metformin was the second (52.9%). However, in 2013, the use of metformin increased to 80.4% of the total antidiabetic prescriptions. The use of dipeptidyl peptidase-4 (DPP-4) inhibitor increased remarkably after release in late 2008 and composed one-third of the market share with 1 million prescriptions (38.4%) in 2013. Among the prescriptions for monotherapy, only 13.0% were metformin in 2002, but the amount increased to 53.2% by 2013. In contrast, the use of SU declined dramatically from 75.2% in 2002 to 30.6% in 2013. Dual and triple combinations steadily increased from 35.0% and 6.6% in 2002 to 44.9% and 15.5% in 2013, respectively. In 2013, SU with metformin (41.7%) and metformin with DPP-4 inhibitor (32.5%) combination were most frequently prescribed. The total antidiabetic medication cost increased explosively from U.S. $70 million (82.5 billion won) in 2002 to U.S. $4 billion (480 billion won) in 2013.The use of antidiabetic agents and their costs have been increasing steadily. Metformin is the most commonly used drug recently. The use of DPP-4 inhibitor increased significantly over the past decade, whereas the use of SU decreased. However, SUs still remain the most commonly prescribed second-line agents with metformin in 2013. PMID- 27399083 TI - Fatal subarachnoid hemorrhage following ischemia in vertebrobasilar dolichoectasia. AB - Vertebrobasilar dolichoectasia (VBD) is a chronic disorder with various cerebrovascular and compressive manifestations, involving subarachnoid hemorrhage (SAH). Occurrence of SAH shortly after worsening of clinical VBD symptoms has occasionally been reported. The goal of the study was to examine this association, in particular its pathophysiology, clinical precursor signs, time course, and outcome.To this end, in a retrospective multicenter study, we analyzed 20 patients with VBD and SAH in regard to preceding clinical symptoms, presence of vertebrobasilar thrombosis and ischemia, outcome and neuropathological correlates.Median age of the 7 female and 13 male patients was 70 years (interquartile range [IQR] 18.3 years). Fourteen patients (70%) presented with new or acutely worsening posterior fossa signs at a median of 3 days prior to SAH (IQR 2, range 0.5-14). A thrombus within the VBD was detected in 12 patients (60%). Thrombus formation was associated with clinical deterioration (chi = 4.38, P = 0.04) and ponto-cerebellar ischemia (chi = 8.09, P = 0.005). During follow-up after SAH, 13 patients (65%) died, after a median survival time of 24 hours (IQR 66.2, range 2-264 hours), with a significant association between proven ponto-cerebellar ischemia and case fatality (chi = 6.24, P = 0.01).The data establish an association between clinical deterioration in patients with VBD, vertebrobasilar ischemia, and subsequent SAH. Antithrombotic treatment after deterioration appears controversial and SAH outcome is frequently fatal. Our data also indicate a short window of 3 days that may allow for evaluating interventional treatment, preferably within randomized trials. PMID- 27399084 TI - A nomogram for predicting survival of nasopharyngeal carcinoma patients with metachronous metastasis. AB - Patients with metachronous metastatic nasopharyngeal carcinoma (NPC) differ significantly in survival outcomes. The aim of this study is to build a clinically practical nomogram incorporating known tumor prognostic factors to predict survival for metastatic NPC patients in epidemic areas.A total of 860 patients with metachronous metastatic nasopharyngeal carcinoma were analyzed retrospectively. Variables assessed were age, gender, body mass index, Karnofsky Performance Status (KPS), Union for International Cancer Control (UICC) T and N stages, World Health Organization (WHO) histology type, serum lactate dehydrogenase (sLDH) level, serum Epstein-Barr virus (EBV) level, treatment modality, specific metastatic location (lung/liver/bone), number of metastatic location(s) (isolated vs multiple), and number of metastatic lesion(s) in metastatic location(s) (single vs multiple). The independent prognostic factors for overall survival (OS) by Cox-regression model were utilized to build the nomogram.Independent prognostic factors for OS of metastatic NPC patients included age, UICC N stage, KPS, sLDH, number of metastatic locations, number of metastatic lesions, involvement of liver metastasis, and involvement of bone metastasis. Calibration of the final model suggested a c-index of 0.68 (95% confidence interval [CI], 0.65-0.69). Based on the total point (TP) by nomogram, we further subdivided the study cohort into 4 groups. Group 1 (TP < 320, 208 patients) had the lowest risk of dying. Discrimination was visualized by the differences in survival between these 4 groups (group 2/group 1: hazard ratio [HR] = 1.61, 95%CI: 1.24-2.09; group 3/group 1: HR = 2.20, 95%CI: 1.69-2.86; and group 4/group 1: HR = 3.66, 95%CI: 2.82-4.75).The developed nomogram can help guide the prognostication of patients with metachronous metastatic NPC in epidemic areas. PMID- 27399085 TI - The effect of interventions targeting screen time reduction: A systematic review and meta-analysis. AB - Previous studies have evaluated the effectiveness of interventions aimed at screen time reduction, but the results have been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to summarize the accumulating evidence of the impact of interventions targeting screen time reduction on body mass index (BMI) reduction and screen time reduction. The PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs on the effect of interventions targeting screen time reduction. The primary and secondary outcomes were the mean difference between the treatment and control groups in the changes in BMI and changes in screen viewing time. A random effects model was used to calculate the pooled mean differences. Fourteen trials including 2238 participants were assessed. The pooled analysis suggested that interventions targeting screen time reduction had a significant effect on BMI reduction (-0.15 kg/m, P < 0.001, I = 0) and on screen time reduction (-4.63 h/w, P = 0.003, I = 94.6%). Subgroup analysis showed that a significant effect of screen time reduction was observed in studies in which the duration of intervention was <7 months and that the types of interventions in those studies were health promotion curricula or counseling. Interventions for screen time reduction might be effective in reducing screen time and preventing excess weight. Further rigorous investigations with larger samples and longer follow-up periods are still needed to evaluate the efficacy of screen time reduction both in children and in adults. PMID- 27399086 TI - Association between the interleukin-6 genetic polymorphism 174 G/C and thrombosis disorder risk: Meta-analysis of 10,549 cases and 19,316 controls. AB - Studies investigating the association between interleukin-6 (IL-6) gene-174 G/C polymorphism (rs1800795) and thrombosis disorder risk reported conflicting results. The aim of our study was to assess the association between the IL-6 gene 174 G/C polymorphisms and the risk of thrombosis disorders.Thirty four case control studies in 29 articles with 29,865 individuals were incorporated in this meta-analysis by searching the public databases including Medline, Embase, and ISI Web of Science databases as of June 1st, 2015. The odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of the association.By pooling all studies, there was marginal association between and the risk of thrombotic disorders (1.09[0.97-1.22]), arterial thrombotic disorders (1.08[0.95-1.23]), and myocardial infarction (MI, 1.14[0.99-1.32]) under dominant genetic effect (C carriers vs GG). In subgroup analyses stratified by ethnicity, study scale, thrombotic category, and country, the results indicated that IL-6 gene-174 G/C polymorphism was significantly associated with increased risk of thrombotic disorders given the conditional such as Asians, large sample-sized, MI, population-based, and Indian studies (C carriers vs GG: 1.39 [1.13-1.72] and C allele vs G allele: 1.36 [1.18-1.56] for Asian; C carriers vs GG: 1.15 [1.01 1.31] and C allele vs G allele: 1.12 [1.01-1.23] for large sample-sized studies; C allele vs G allele: 1.10 [1.03-1.18] for population-based studies; and C carriers vs GG: 1.40 [1.19-1.65] for Indian studies). We did not observe significant association between IL-6-174 G/C and the risk of Caucasians, small sample-sized studies, stroke and venous studies, and other country studies.This meta-analysis suggests that IL-6 gene-174 G/C polymorphism may be marginally associated with risk of thrombotic disorders, arterial disorders, MI especially for Asian, Indian, population-based, and large sample-sized studies. More studies with larger sample size and well-designed studies might be warranted. PMID- 27399087 TI - Characterization of the Myocarditis during the worst outbreak of dengue infection in China. AB - Myocarditis is a common complication of severe dengue infection. However, data about prevalence and characterization of myocarditis in dengue are still lacking. In 2014, the worst outbreak of dengue in the last two decades in China occurred. In this study, we described the clinical and laboratory diagnostic features of dengue with myocarditis. Totally, 1782 diagnosed dengue patients were admitted from August to October, 2014, all of whom were subjected to electrocardiogram, ultrasound cardiogram, and cardiac enzyme test. About 201 cases of dengue patients were diagnosed with myocarditis and the prevalence of myocarditis in hospitalized dengue was 11.28%. The prevalence of myocarditis in nonsevere dengue with warning signs and severe dengue [NSD(WS+)/SD] and nonsevere dengue without warning signs [NSD(WS-)] was 46.66% and 9.72%, respectively. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac symptoms, supraventricular tachycardia (14.29% vs. 0%, P < 0.001), atrial fibrillation (25.71% vs. 10.24%, P = 0.019) and heart failure compared with NSD (WS-) patients with myocarditis. About 150 cases of dengue patients without myocarditis in the same period of time in department of Cardiology were recruited as control group. The proportion of NSD(WS+)/SD in dengue patients with and without myocarditis was 17.41% and 2.53%, respectively. Dengue patients with myocarditis experienced longer hospital stay than those without myocarditis (7.17 +/- 4.64 vs. 5.98 +/- 2.69, P = 0.008). There was no difference between patients with and without myocarditis in the proportion of symptoms, auxiliary methods abnormality, arrhythmia, and heart failure on the discharge day. Our study demonstrates the prevalence of myocarditis in worst outbreak of dengue in China was 11.28% and the incidence of myocarditis increased with the severity of dengue. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac complication compared with NSD (WS-) patients with myocarditis. The prognosis of dengue patients with and without myocarditis had no significant difference even if myocarditis patients experienced longer hospital stay. PMID- 27399088 TI - The characteristics and prognostic value of signet ring cell histology in gastric cancer: A retrospective cohort study of 2199 consecutive patients. AB - Although signet ring cell cancer (SRCC) has long been regarded as an adverse prognostic factor of gastric cancer, the findings of existing studies on this issue are inconsistent. We conducted a retrospective cohort study of 2199 consecutive patients with gastric cancer treated in a tertiary cancer hospital in Beijing, China, 1994 to 2013. The characteristics of SRCC and non-SRCC were compared. The prognostic effects of SRCC and other important clinicopathological factors on overall survival were evaluated by both univariate and multivariate Cox regression analyses and expressed as hazard ratio (HR) with 95% confidence interval (CI). SRCC accounted for 16.1% of gastric cancer, increasing from 6% to 20% over the last 2 decades, and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. SRCC (HR: 1.387, 95% CI: 1.177-1.634), stage (HR: 1.752, 95% CI: 1.458-2.106), surgery (palliative resection: HR: 0.712, 95% CI: 0.590-0.859; curative resection: HR: 0.490, 95% CI: 0.380-0.633), performance status (HR: 1.849, 95% CI: 1.553-2.201), and age (HR: 1.070, 95% CI: 1.001-1.143) were independent prognostic factors for gastric cancer, whereas time period of diagnosis, sex, and tumor location were not statistically significantly associated with overall survival. Subgroup analyses showed that the prognostic value of SRCC did not vary much with age, sex, performance status, stage, and surgery and chemotherapy status. As compared with non-SRCC, SRCC accounted for increasingly more of gastric cancer and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. It was an independent prognostic factor associated with worse survival in gastric cancer. PMID- 27399089 TI - Racial patterns of patients with primary mediastinal large B-cell lymphoma: SEER analysis. AB - The aim of this study is to investigate the incidence and clinical outcomes of primary mediastinal large B-cell lymphoma (PMBL).Here we did a retrospective analysis using the surveillance, epidemiology, and end results (SEER) database to analyze the incidences and survival of patients with PMBL diagnosed during 2001 2012 among major ethnic groups.During 2001-2012, a total of 426 PMBL patients were identified, including 336 whites, 46 blacks, and 44 others. The incidence rates of female to male ratios in white, black, and other were 1.4938, 1.1202, and 1.7303 respectively, suggesting that the female-prominent disease occurrence was seen only in whites and others, but not in black population. Compared to white, the other had a worse 5-year overall survival (OS); however, factors including age, race, socioeconomic status, and stage associated with OS showed no significant difference among ethnic groups; thus, biology factors should be explored to explain the racial difference in OS.In conclusion, our findings revealed diversities in demographic features and prognosis among different racial groups. PMID- 27399090 TI - Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study. AB - Health-related quality of life (HRQoL) is impaired in HIV/HCV-coinfected patients (HIV/HCV) and further decreased by interferon (IFN)-based therapies. We aimed to investigate the impact of IFN- and ribavirin (RBV)-free therapies on HRQoL and fatigue.Thirty-three HIV/HCV-coinfected patients who underwent HCV therapy with sofosbuvir in combination with daclatasvir or ledipasvir were retrospectively studied and compared to 17 patients who received boceprevir (BOC)/PEGIFN/RBV. HRQoL (mental [MCS] and physical [PCS] component score) and fatigue were assessed using the SF-36 (Short Form 36 Health Survey) and the FSS (Fatigue Severity Scale), respectively. HRQoL/fatigue was evaluated at baseline (BL), midway, and 12 weeks after the end of treatment (FU).At BL, both domains of HRQoL as well as the severity of fatigue were significantly impaired in HIV/HCV, when compared to a healthy population. Already during treatment, IFN/RBV-free therapy improved physical health (PCS: 41.4 +/- 9.7 vs. 47.0 +/- 11.2; P < 0.01) and reduced fatigue (37.8 +/- 14.0 vs. 31.9 +/- 15.2; P = 0.01), whereas we observed a substantial worsening of both factors in patients treated with BOC/PEGIFN/RBV. Since these improvements were maintained, patients treated with IFN/RBV-free therapy reported an improvement in physical health (PCS: 41.4 +/- 9.7 vs. 45.8 +/ 12.7; P < 0.01) and fatigue (37.8 +/- 14.0 vs. 30.9 +/- 14.8; P = 0.04) at FU. While AIDS-patients had a higher severity of fatigue at BL and showed a reduction of fatigue (42.5 +/- 14.0 vs. 31.6 +/- 15.7; P = 0.01), mental health only improved in patients without AIDS (MCS: 35.7 +/- 5.3 vs.40.7 +/- 6.4; P = 0.04). HIV/HCV with severe fatigue at BL (>median BL-FSS) showed most pronounced improvements in severity of fatigue (49.7 +/- 7.0 vs. 32.0 +/- 16.7; P < 0.01).In contrast to IFN-based regimens, highly effective and well-tolerated IFN-/RBV-free regimens improve HRQoL (especially physical health) and fatigue already during treatment. All patients with HIV/HCV coinfection should be considered for HCV treatment; however, patients with severe fatigue should be prioritized. PMID- 27399091 TI - Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma. AB - Serum enzymes, including lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), have recently been reported to play important roles in tumor growth. Increases in LDH and ALP have been confirmed to predict poor prognosis in patients with various cancers. However, their prognostic value in pancreatic cancer has not been well studied. Therefore, we reviewed the preoperative data on LDH and ALP in 185 pancreatic ductal adenocarcinoma (PDAC) patients who underwent surgery between July 2005 and December 2010 to explore the prognostic value of these markers. The cutoff points were determined based on the upper limit of their normal values. The Chi-square test was used to analyze the relationships between LDH/ALP and clinical characteristics. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). We found that elevation of LDH was related to carbohydrate antigen 19-9 (CA19-9), lymph node involvement, tumor size, TNM, distant metastasis, and recurrence. Additionally, ALP was correlated to perineural invasion. After multivariate analysis, LDH and ALP were identified as independent prognostic factors for DFS and OS, and elevation of LDH/ALP was correlated with poor DFS and OS. Notably, there was a positive correlation between LDH and ALP. The predictive power of LDH combined with ALP was more sensitive than that of either one alone. Therefore, we conclude that the preoperative LDH and ALP values are prognostic factors for PADC, and the prognostic accuracy of testing can be enhanced by the combination of LDH and ALP. PMID- 27399092 TI - Genetic variants of the CYP1B1 gene as predictors of biochemical recurrence after radical prostatectomy in localized prostate cancer patients. AB - Clinically localized prostate cancer is curative. Nevertheless many patients suffered from biochemical recurrence (BCR) after radical prostatectomy (RP). Mounting evidence suggest that estrogen and xenobiotic carcinogens play an essential role in progression of prostate cancervia oxidative estrogen metabolism. CYP1B1 is an enzyme involved in the hydroxylation of estrogens, a reaction of key relevance in estrogen metabolism. Given the role of CYP1B1 in the oxidative metabolism of endogenous/exogenous estrogen and compounds, CYP1B1 polymorphisms have the potential to modify its expression and subsequently lead to progression. We hypothesize that genetic variants of the CYP1B1 gene may influence clinical outcome in clinically localized prostate cancer patients. In this cohort study, we genotyped 9 tagging single nucleotide polymorphisms (SNPs) from the CYP1B1 gene in 312 patients treated with RP. For replication, these SNPs were genotyped in an independent cohort of 426 patients. The expression level of CYP1B1 in the adjacent normal prostate tissues was quantified by reverse transcription and real-time polymerase chain reaction. Kaplan-Meier analysis and Cox proportional hazard models were utilized to identify SNPs that correlated with BCR. CYP1B1 rs1056836 was significantly associated with BCR (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.40-0.89, P = 0.002) and relative CYP1B1 mRNA expression. Our findings suggest inherited genetic variation in the CYP1B1 gene may contribute to variable clinical outcomes for patients with clinically localized prostate cancer. PMID- 27399093 TI - Cause of death in Chinese Takayasu arteritis patients. AB - To analyze the causes of death and the related risk factors for in-patients with Takayasu arteritis (TAK) admitted to a referral center of China during 1983 to 2014.The medical charts of 12 deceased TAK patients (10 women, 2 men) were reviewed by two senior rheumatologists. The demographic data, clinical manifestations, angiographic presentations, and the direct causes of death were analyzed retrospectively. Medical records of 40 TAK patients (32 women, 8 men) were selected as controls by age and sex matching method from 81 patients who were sampled isometrically from 810 successively admitted TAK in-patients of the same center during the same period. In addition to the comparison of clinical manifestations between the two groups, binary logistic regression was conducted to explore the related risk factors of mortality of TAK.Twelve patients died at the median age of 33.5 (ranging from 13 to 68 years old). The median survival time was 102.5(ranging from 6 to 567) months. The direct causes of death were heart failure in 5 (5/12, 41.7%), hemorrhage in 2 (2/12, 16.7%), pulmonary infection in 2 (2/12, 16.7%), sudden death in 1 (1/12, 8.3%), postoperative complication in 1 (1/12, 8.3%), and end-stage malignancy in 1 (1/12, 8.3%). Ischemia (4/12, 33.3%) and hemorrhage (4/12, 33.3%) were the two most common presentations in deceased patients. Eight patients had received surgical procedures related to TAK changes. Among them, 2 patients died after surgical procedure, the other 6 patients died later of non-operation-related causes. Compared with the control group (n = 40), patients in the deceased group had longer disease duration (P = 0.017), higher proportion of active disease (P = 0.020), secondary hypertension (P = 0.004), and congestive heart failure (P = 0.017). A model of binary logistic regression had revealed that secondary hypertension (odds ratio [OR] = 9.333, 95% confidence interval [CI]: 1.721 - 50.614, P = 0.010), congestive heart failure (OR = 5.667, 95% CI: 1.248 - 25.734, P = 0.025), and longer disease duration (OR = 1.007, 95% CI: 1.001 - 0.735, P = 0.027) were risk factors for TAK mortality. Active disease (OR = 0.167, 95% CI: 0.038 - 50.614, P = 0.018) was negatively associated with death of TAK.Heart failure is the leading cause of death in TAK patients, followed by ischemia and pulmonary infection. Early deaths occur postoperatively but become rare later after the procedure. Well-control of hypertension, and prevention of congestive heart failure may improve the long-term prognosis. PMID- 27399094 TI - Acute fibrinous and organizing pneumonia: A report of 13 cases in a tertiary university hospital. AB - INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare diffuse pulmonary disease, but it is not yet known whether it is a distinct form of interstitial pneumonia or simply a reflection of a tissue sampling issue. METHODS: Cross-sectional evaluation of clinical and radiological findings, treatments, and outcomes for patients with histologically confirmed AFOP at a tertiary university hospital between 2002 and 2015. RESULTS: Thirteen patients (7 women, 53.8%) with a mean +/- SD age of 53.5 +/- 16.1 years were included. The main symptoms were fever (69.2%), cough (46.2%), and chest pain (30.8%). All patients presented a radiological pattern of consolidation and 5 (38.5%) had simultaneous ground-glass areas. Histology was obtained by computed tomography guided transthoracic biopsy in 61.5% of cases and by surgical lung biopsy in the remaining cases. Several potential etiologic factors were identified. Eight patients (61.5%) had hematologic disorders and 3 had undergone an autologous hematopoietic cell transplant. Two (15.4%) had microbiologic isolates, 5 (38.4%) had drug-induced lung toxicity, and 2 (15.4%) were classified as having idiopathic AFOP. In addition to antibiotics and diuretics used to treat the underlying disease, the main treatment was corticosteroids, combined in some cases with immunosuppressants. Median survival was 78 months and 6 patients (46.2%) were still alive at the time of analysis. CONCLUSION: Our findings for this series of patients confirm that AFOP is a nonspecific reaction to various agents with a heterogeneous clinical presentation and clinical course that seems to be influenced mainly by the severity of the underlying disorder. PMID- 27399095 TI - Prospective clinical observational study evaluating gender-associated differences of preoperative pain intensity. AB - Previous studies reported conflicting results concerning different pain perceptions of men and women. Recent research found higher pain levels in men after major surgery, contrasted by women after minor procedures. This trial investigates differences in self-reported preoperative pain intensity between genders before surgery.Patients were enrolled in 2011 and 2012 presenting for preoperative evaluation at the anesthesiological assessment clinic at Charite University hospital. Out of 5102 patients completing a computer-assisted self assessment, 3042 surgical patients with any preoperative pain were included into this prospective observational clinical study. Preoperative pain intensity (0-100 VAS, visual analog scale) was evaluated integrating psychological cofactors into analysis.Women reported higher preoperative pain intensity than men with median VAS scores of 30 (25th-75th percentiles: 10-52) versus 21 (10-46) (P < 0.001). Adjusted multiple regression analysis showed that female gender remained statistically significantly associated with higher pain intensity (P < 0.001). Gender differences were consistent across several subgroups especially with varying patterns in elderly. Women scheduled for minor and moderate surgical procedures showed largest differences in overall pain compared to men.This large clinical study observed significantly higher preoperative pain intensity in female surgical patients. This gender difference was larger in the elderly potentially contradicting the current hypothesis of a primary sex-hormone derived effect. The observed variability in specific patient subgroups may help to explain heterogeneous findings of previous studies. PMID- 27399096 TI - Two-dimensional assessment of submillimeter cancer-free margin area in colorectal liver metastases. AB - The aim of the study is to evaluate the prognostic impact of the extent of submillimeter or zero surgical margin (SubMM) area among the patients who underwent liver resection for colorectal liver metastases (CRLM).The influence of suboptimal margin width of <1 mm on long-term outcome is unclear.A total of 423 liver resections for CRLM were performed at Japanese Red Cross Medical Center between 2007 and 2015. Among them, we identified 235 patients who underwent curative initial liver resection and classified them into 2 groups: R0 (margin: >=1 mm) and R1 (SubMM). The R1 group was further divided into 2 groups by the extent of SubMM area: small SubMM area (<=4 cm) and broad SubMM area (>4 cm).The median tumor number was 4 (range 1-97), 23% had solitary and 37% had 8 or more number of metastases. With a median follow-up period of 30 months, the overall 1 , 3-, 5-year survival for R0 (n = 72) versus R1 (n = 163) groups were 98.4% vs 87.5%, 75.5% versus 57.1%, and 50.1% versus 36.6%, respectively (P = 0.004). After propensity score analysis allowing for matching the tumor number (<8 vs 8 or more), tumor size, and serum carcinoembryonic antigen level, the DFS and OS were significantly higher in the small SubMM area group (P = 0.024, P = 0.049), respectively.Although wide margins >1 mm should be attempted whenever possible, reducing the extent of SubMM area (<=4 cm) can contribute to better long-term outcome when wide margin is not practicable. PMID- 27399097 TI - Disrupted resting-state insular subregions functional connectivity in post traumatic stress disorder. AB - Post-traumatic stress disorder (PTSD) is suggested to be a structural and functional abnormality in the insula. The insula, which consists of distinct subregions with various patterns of connectivity, displays complex and diverse functions. However, whether these insular subregions have different patterns of connectivity in PTSD remains unclear. Investigating the abnormal functional connectivity of the insular subregions is crucial to reveal its potential effect on diseases specifically PTSD. This study uses a seed-based method to investigate the altered resting-state functional connectivity of insular subregions in PTSD. We found that patients with PTSD showed reduced functional connectivity compared with healthy controls (HCs) between the left ventral anterior insula and the anterior cingulate cortex. The patients with PTSD also exhibited decreased functional connectivity between the right posterior insula and left inferior parietal lobe, and the postcentral gyrus relative to HCs. These results suggest the involvement of altered functional connectivity of insular subregions in the abnormal regulation of emotion and processing of somatosensory information in patients with PTSD. Such impairments in functional connectivity patterns of the insular subregions may advance our understanding of the pathophysiological basis underlying PTSD. PMID- 27399098 TI - Preoperative prognostic nutritional index predicts postoperative surgical site infections in gastrointestinal fistula patients undergoing bowel resections. AB - Recent studies have implied a prognostic value of the prognostic nutritional index (PNI) in postoperative septic complications of elective colorectal surgeries. However, the evaluation of PNI in contaminated surgeries for gastrointestinal (GI) fistula patients is lack of investigation. The purpose of this study was to explore the predictive value of PNI in surgical site infections (SSIs) for GI fistula patients undergoing bowel resections.A retrospective review of 290 GI patients who underwent intestinal resections between November 2012 and October 2015 was performed. Univariate and multivariate analyses were conducted to identify risk factors for SSIs, and receiver operating characteristic cure was used to quantify the effectiveness of PNI.SSIs were diagnosed in 99 (34.1%) patients, with incisional infection identified in 54 patients (18.6%), deep incisional infection in 13 (4.5%), and organ/space infection in 32 (11.0%). receiver operating characteristic curve analysis defined a PNI cut-off level of 45 corresponding to postoperative SSIs (area under the curve [AUC] = 0.72, 76% sensitivity, 55% specificity). Furthermore, a multivariate analysis indicated that the PNI < 45 [odd ratio (OR): 2.24, 95% confidence interval (CI): 1.09-4.61, P = 0.029] and leukocytosis (OR: 3.70, 95% CI: 1.02-13.42, P = 0.046) were independently associated with postoperative SSIs.Preoperative PNI is a simple and useful marker to predict SSIs in GI fistula patients after enterectomies. Measurement of PNI is therefore recommended in the routine assessment of patients with GI fistula receiving surgical treatment. PMID- 27399099 TI - Expression profile of SIX family members correlates with clinic-pathological features and prognosis of breast cancer: A systematic review and meta-analysis. AB - Sineoculis homeobox homolog (SIX) family proteins, including SIX1, SIX2, SIX3, SIX4, SIX5, and SIX6, have been implicated in the initiation and progression of breast cancer, but the role of each member in breast tumor is not fully understood. We conducted a systematic review and meta-analysis to evaluate the association between the mRNA levels of all 6 members and clinic-pathological characteristics and clinical outcome of breast cancer patients based on the PRISMA statement criteria.ArrayExpress and Oncomine were searched for eligible databases published up to December 10, 2015. The association between the mRNA expression of SIX family members and clinic-pathological features and prognosis was measured by the odds ratio (OR), hazard ratio (HR), and the corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed using STATA software.In total, 20 published Gene Expression Omnibus (GEO) databases with 3555 patients were analyzed. Our analysis revealed that patients with SIX1 overexpression had worse overall survival (OS) (HR: 1.28, 95% CI: 1.03 1.58) and shorter relapse-free survival (RFS) (HR: 1.28, 95% CI: 1.05-1.56), and much worse prognosis for luminal breast cancer patients with SIX1 overexpression (OS: HR: 1.64, 95% CI: 1.13-2.39; RFS: HR: 1.43, 95% CI: 1.06-1.93). We found that patients with higher SIX2 level had shorter time to both relapse and metastasis. However, high SIX3 mRNA level was a protective factor for OS and RFS of basal-like breast cancer patients.Our study suggested that members of SIX family played distinct roles in breast cancer. Detailed analysis of the expression of the SIX family members might provide useful information to predict breast cancer progression and prognosis. PMID- 27399100 TI - Analysis of factors influencing the degree of detectability on diffusion-weighted MRI and diffusion background signals in patients with invasive breast cancer. AB - To determine the factors influencing the degree of detectability of lesions and diffusion background signals on magnetic resonance diffusion-weighted imaging (DWI) in invasive breast cancer.Institutional review board approval was obtained and patient consent was waived. Patients with newly diagnosed invasive ductal carcinoma, who underwent preoperative breast magnetic resonance imaging with DWI were included in this study (n = 167). Lesion detectability on DWI and contrast enhanced subtracted T1-weighted images, the degree of background parenchymal enhancement (BPE), and diffusion background signal were qualitatively rated. Detectability of lesions on DWI was compared with clinicopathological findings including menopausal status, mammographic density, and molecular subtype of breast cancer. Multivariate linear regression analysis was performed to determine variables independently associated with detectability of lesions on DWI and diffusion background signals.Univariate analysis showed that the detectability of lesions on DWI was significantly associated with lesion size (P = 0.001), diffuse background signal (P < 0.0001), and higher detectability scores for contrast enhanced T1-weighted subtraction images (P = 0.000). The degree of diffusion background signal was significantly affected by age (P < 0.0001), BPE (P < 0.0001), mammographic density (P = 0.002), and menopausal status (P < 0.0001). On multivariate analysis, the diffusion background signal (P < 0.0001) and histologic grade (P < 0.0001) were correlated with the detectability on DWI of invasive breast cancer. Only BPE was correlated with the amount of diffusion background signal on DWI (P < 0.0001).For invasive breast cancers, detectability on DWI was significantly affected by the diffusion background signal. BPE, menopausal status, menstrual cycle, or mammographic density did not show statistically significant correlation with the diffusion detectability of lesions on DWI. PMID- 27399101 TI - Preoperative gamma-glutamyl transpeptidase to platelet ratio (GPR) is an independent prognostic factor for HBV-related hepatocellular carcinoma after curative hepatic resection. AB - Liver fibrosis and cirrhosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after treatment. The gamma-glutamyl transpeptidase to platelet ratio (GPR) is reported to predict significant liver fibrosis and cirrhosis. The aim of this study was to investigate the predictive value of preoperative GPR on the recurrence and survival of patients with HCC who underwent curative hepatectomy.A retrospective review of demographics, medical records, and prognosis of patients with hepatitis B virus (HBV)-related HCC was performed. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier method, and the log-rank test was used to analyze differences in recurrence and survival. Univariate and multivariate analyses were used for significance of prognostic factor.A total of 357 patients with HBV-related HCC were included in this analysis. The preoperative GPR was associated with recurrence and survival rates, independent of HCC progression or tumor marker levels, in a multivariate analysis. OS was higher in patients with a GPR <0.84 versus >=084 (5-year survival rates 58.6% vs. 38.5%; P < 0.001). DFS was also worse in patients with a GPR >=0.84 than in those with GPR <0.84 (5-year recurrence rates 42.8% vs. 22.8%; P < 0.001).GPR score of >=0.84 represents a major risk factor for the poor prognosis for HBV-related HCC after hepatic resection, and GPR served as an independent predictive factor for HBV-related HCC OS. PMID- 27399102 TI - Association between gastroesophageal reflux disease and coronary heart disease: A nationwide population-based analysis. AB - In this study, we aimed to determine the association between gastroesophageal reflux disease (GERD) and subsequent coronary heart disease (CHD) development, if any, and to evaluate whether longer use of proton pump inhibitors (PPIs) increases the risk of CHD.Patients diagnosed with GERD between 2000 and 2011 were identified as the study cohort (n = 12,960). Patients without GERD were randomly selected from the general population, frequency-matched with the study group according to age, sex, and index year, and evaluated as the comparison cohort (n = 51,840). Both cohorts were followed up until the end of 2011 to determine the incidence of CHD. The risk of CHD was evaluated in both groups by using Cox proportional hazards regression models.The GERD patients had a greater probability of CHD than the cohort without GERD did (log-rank test, P < 0.001 and 11.8 vs 6.5 per 1000 person-years). The GERD cohort had a higher risk of CHD than the comparison cohort did after adjustment for age, sex, hypertension, diabetes, hyperlipidemia, alcohol-related illness, stroke, chronic obstructive pulmonary disease, asthma, biliary stone, anxiety, depression, chronic kidney disease, and cirrhosis (adjusted hazard ratio [aHR]: 1.49, 95% confidence interval [CI]: 1.34 1.66). The risk of CHD was greater for the patients treated with PPIs for more than 1 year (aHR = 1.67, 95% CI = 1.34-2.08) than for those treated with PPIs for <1 year (aHR = 1.56, 95% CI = 1.39-1.74).Our population-based cohort study results indicate that GERD was associated with an increased risk of developing CHD, and that PPI use for more than 1 year might increase the risk of CHD. PMID- 27399103 TI - Outcomes of off- and on-hours admission in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: A retrospective observational cohort study. AB - Studies evaluating the outcomes of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) are scarce, particularly in China. The purpose of present study was therefore to compare the impact of off-hours and on-hours admission on clinical outcomes in STEMI patients from China.We retrospectively analyzed 1594 patients from 4 hospitals. Of these, 903 patients (56.65%) were admitted during off-hours (weekdays from 18:00 to 08:00, weekends and holidays) and 691 (43.35%) were during on-hours (weekdays from 08:00 to 18:00).Patients admitted during off-hours had higher thrombolysis in myocardial infarction risk score (4.67 +/- 2.27 vs 4.39 +/- 2.10, P = 0.012) and longer door-to-balloon time (72 [50-96] vs 64 [42 92] minutes, P < 0.001) than those admitted during on-hours. Off-hours admission had no association with in-hospital (unadjusted odds ratio 2.069, 95% confidence interval [CI] 0.956-4.480, P = 0.060) and long-term mortality (unadjusted hazards ratio [HR] 1.469, 95%CI 0.993-2.173, P = 0.054), even after adjustment for confounders. However, long-term outcomes, the composite of deaths and other adverse events, differed between groups with an unadjusted HR of 1.327 (95%CI, 1.102-1.599, P = 0.003), which remained significant in regression models. In a subgroup analysis, off-hours admission was associated with higher long-term mortality in the high-risk subgroup (unadjusted HR 1.965, 95%CI 1.103-3.512, P = 0.042), but not in low- and moderate-risk subgroups.This study showed no association between off-hours admission and in-hospital and long-term mortality. Stratified analysis indicated that off-hours admission was significantly associated with long-term mortality in the high-risk subgroup. PMID- 27399104 TI - Feasibility of Free-breathing CCTA using 256-MDCT. AB - Usually, coronary computed tomography angiography (CCTA) is performed during breath-holding to reduce artifact caused by respiration. The objective of this study was to evaluate the feasibility of free-breathing CCTA compared to breath holding using CT scanner with wide detector. To evaluate the feasibility of CCTA during free-breathing using a 256-MDCT. In 80 patients who underwent CCTA, 40 were performed during breath-holding (group A), and the remaining 40 during free breathing (group B). The quality scores for coronary arteries were analyzed and defined as: 3 (excellent), 2 (good), and 1 (poor). The image noise, signal-to noise ratio and effective radiation dose as well as the heart rate variation were compared. The noise, signal-to-noise ratio, and effective radiation dose were not significantly different between the 2 groups. The mean heart rate variation between planning and scanning for group A was 7 +/- 7.6 bpm, and larger than 3 +/ 2.6 bpm for group B (P = 0.012). Quality scores of the free-breathing group were better than those of the breath-holding group (group A: 2.55 +/- 0.64, group B: 2.85 +/- 0.36, P = 0.018). Free-breathing CCTA is feasible on wide detector CT scanner to provide acceptable image quality with reduced heart rate variation and better images for certain patients. PMID- 27399105 TI - Impact of demographic, genetic, and bioimpedance factors on gestational weight gain and birth weight in a Romanian population: A cross-sectional study in mothers and their newborns: the Monebo study (STROBE-compliant article). AB - The present study had 2 objectives, first, to investigate possible relationships between increased gestational weight gain and demographic, clinical, paraclinical, genetic, and bioimpedance (BIA) characteristics of Romanian mothers, and second, to identify the influence of predictors (maternal and newborns characteristics) on our outcome birth weight (BW).We performed a cross sectional study on 309 mothers and 309 newborns from Romania, divided into 2 groups: Group I-141 mothers with high gestational weight gain (GWG) and Group II 168 mothers with normal GWG, that is, control group.The groups were evaluated regarding demographic, anthropometric (body mass index [BMI], middle upper arm circumference, tricipital skinfold thickness, weight, height [H]), clinical, paraclinical, genetic (interleukin 6 [IL-6]: IL-6 -174G>C and IL-6 -572C>G gene polymorphisms), and BIA parameters.We noticed that fat mass (FM), muscle mass (MM), bone mass (BM), total body water (TBW), basal metabolism rate (BMR) and metabolic age (P < 0.001), anthropometric parameters (middle upper arm circumference, tricipital skinfold thickness; P < 0.001/P = 0.001) and hypertension (odds ratio = 4.65, 95% confidence interval: 1.27-17.03) were higher in mothers with high GWG. BW was positively correlated with mothers' FM (P < 0.001), TBW (P = 0.001), BMR (P = 0.02), while smoking was negatively correlated with BW (P = 0.04). Variant genotype (GG+GC) of the IL-6 -572C>G polymorphism was higher in the control group (P = 0.042).We observed that high GWG may be an important predictor factor for the afterward BW, being positively correlated with FM, TBW, BMR, metabolic age of the mothers, and negatively with the mother's smoking status. Variant genotype (GG+GC) of the IL-6 -572C>G gene polymorphism is a protector factor against obesity in mothers. All the variables considered explained 14.50% of the outcome variance. PMID- 27399106 TI - High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs: A multi-centre point prevalence survey. AB - There is scarce information regarding hospital-acquired infections (HAIs) among children in resource-constrained settings. This study aims to measure prevalence of HAIs in Vietnamese pediatric hospitals.Monthly point prevalence surveys (PPSs) in 6 pediatric intensive care units (ICUs) in 3 referral hospitals during 1 year.A total of 1363 cases (1143 children) were surveyed, 59.9% male, average age 11 months. Admission sources were: other hospital 49.3%, current hospital 36.5%, and community 15.3%. Reasons for admission were: infectious disease (66%), noninfectious (20.8%), and surgery/trauma (11.3%). Intubation rate was 47.8%, central venous catheter 29.4%, peripheral venous catheter 86.2%, urinary catheter 14.6%, and hemodialysis/filtration 1.7%. HAI was diagnosed in 33.1% of the cases: pneumonia (52.2%), septicemia (26.4%), surgical site infection (2%), and necrotizing enterocolitis (2%). Significant risk factors for HAI included age under 7 months, intubation and infection at admission. Microbiological findings were reported in 212 cases (43%) with 276 isolates: 50 Klebsiella pneumoniae, 46 Pseudomonas aeruginosa, and 39 Acinetobacter baumannii, with carbapenem resistance detected in 55%, 71%, and 65%, respectively. Staphylococcus aureus was cultured in 18 cases, with 81% methicillin-resistant Staphylococcus aureus. Most children (87.6%) received antibiotics, with an average of 1.6 antibiotics per case. Colistin was administered to 96 patients, 93% with HAI and 49% with culture confirmed carbapenem resistance.The high prevalence of HAI with carbapenem resistant gram-negative strains and common treatment with broad-spectrum antibiotics and colistin suggests that interventions are needed to prevent HAI and to optimize antibiotic use. PMID- 27399107 TI - Case report of medical thoracoscopy and endobronchial ultrasound bronchoscopy in the workup of giant solitary fibrous tumor of the pleura. AB - Solitary fibrous tumor of the pleura (SFTP) is a rare tumor of fibroblastic origin. It can be quite vascular, and its surgical management carries the risk of a major intra-operative bleed. The pre-operative use of endobronchial ultrasound (EBUS) to visualize the vascular supply of the tumor has not been reported.We report a case of a patient presenting with progressive shortness of breath and cough who was found to have a very large pleural-based tumor. We describe the use of medical thoracoscopy and EBUS to establish the diagnosis of SFTP and to characterize the blood supply of the tumor.In the future, EBUS may provide an alternative to conventional angiography for both mapping and embolizing tumor blood supply. PMID- 27399108 TI - Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI. AB - To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity. PMID- 27399109 TI - Obturator hernia as a frequent finding during laparoscopic pelvic exploration: A retrospective observational study. AB - Hernia through the obturator canal is usually unsuspected and hence undiagnosed. Patients with obturator hernias present as acute cases of intestinal obstruction secondary to strangulation or incarceration, with high rate of morbidity and mortality due to delayed diagnosis and treatment. The know incidence of obturator hernia is low, representing 0.073% (11 of 15,098) of all hernias repaired at the Mayo Clinic in a retrospective study of 15 years. In this study, we conducted a retrospective analysis of laparoscopic extraperitoneal hernia repairs that were performed between the years 2003 and 2007. All procedures were undertaken by 2 experienced surgeons who performed more than 150 previous surgeries. In 293 patients who underwent repair of bilateral or recurrent inguinal hernia, exploration of the obturator foramen was conducted looking for obturator hernia, which was found in 20 cases (6.82% of patients). The true incidence of obturator hernia is greater than that reported in the literature, and the chances of detecting hernia are greater if an equal number of men and women are scanned could be higher if pelvic scanning was performed. PMID- 27399110 TI - Complete remission of thrombotic microangiopathy after treatment with eculizumab in a patient with non-Shiga toxin-associated bacterial enteritis: A case report. AB - To describe a case of complete remission of thrombotic microangiopathy after treatment with eculizumab in a patient with non-Shiga toxin-associated bacterial enteritis. CASE REPORT: Medical/surgical intensive care unit (ICU) of a university teaching hospital.A 62-year-old man presented to a local hospital with mucous and bloody stool persisting for 1 month and worsening abdominal pain for 2 weeks. He had thrombocytopenia and renal dysfunction and was admitted with a diagnosis of sepsis due to intraabdominal infection. However, he did not respond to antimicrobial therapy, and after 7 days he was transferred to the Chiba University Hospital ICU.Antimicrobial therapy was continued, and continuous hemodiafiltration was initiated on ICU day 3, but the patient's condition deteriorated and he became anuric. Plasma exchange (PE) was initiated on ICU day 11, but anuria and thrombocytopenia persisted. Intravenous eculizumab therapy was initiated on day 26 and resulted in quick recovery of urine output and platelet count and successful discontinuation of renal support.The diagnosis of thrombotic microangiopathy was established by the presence of schistocytes on the peripheral blood smear on ICU day 9. A plasma sample collected prior to initiation of PE showed a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs member 13 (ADAMTS13) activity level of >10% (25.1%). The absence of both Shiga toxin producing E coli in feces and anti-Shiga-toxin antibody in blood led to suspicion of atypical hemolytic uremic syndrome (aHUS). Genetic test identified a nonsynonymous mutation (p.Ala311Val) in the membrane cofactor protein gene (MCP).Although the pathological significance is currently unknown, this mutation may have been the cause of adult-onset aHUS in our patient. In this case, eculizumab was successfully introduced and discontinued, and the patient remained relapse-free after 1 year of follow-up. The duration of eculizumab therapy for patients with aHUS should be determined on a case-by-case basis and possibly according to the causative genetic mutation, even though discontinuation of eculizumab therapy once initiated is not generally recommended. PMID- 27399111 TI - Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure. AB - Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines. Interleukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure. Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it.A total of 1713 adult patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter single nucleotide polymorphisms (SNPs), rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.63-0.90, adjusted P = 0.002) after adjustment for multiple cardiovascular risk factors including age, sex, smoking status, diabetes, hypertension, and dyslipidemia. This association was evident in both ischemic and nonischemic heart failure (P = 0.005 and P = 0.05, respectively). Furthermore, prospective follow-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17RA was significantly associated with cardiovascular mortality (hazard ratio [HR] = 1.28; 95% CI = 1.02-1.59, adjusted P = 0.03) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of congestive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure. These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure pathogenesis and progression. PMID- 27399112 TI - A case report: Clinical application of celiac plexus block in bile duct interventional procedures. AB - Although percutaneous transhepatic biliary drainage (PTBD) and tract dilatation (TD) are very painful procedures, almost all of those procedures have been conducted under local anesthesia and opioid injection due to the lack of manpower and time. Celiac plexus block (CPB) is an interventional technique used for diagnostic and therapeutic purposes in the treatment of abdominovisceral pain. CPB decreases the side effects of opioid medications and enhances analgesia from medications. We present the case of a patient who underwent PTBD and TD under CPB in order to reduce procedure-related abdominal pain.CPB can be a useful alternative technique for pain management during and after biliary interventional procedures, although CPB-induced complications must always be kept in mind. PMID- 27399113 TI - Integrative radiogenomic analysis for genomic signatures in glioblastomas presenting leptomeningeal dissemination. AB - Despite therapeutic advances, the prognosis for glioblastoma (GBM) remains poor. In particular, leptomeningeal dissemination (LMD) has a dismal prognosis. The aim of this study was to identify tumor molecular phenotype, which has a great propensity to develop LMD. Between May 2004 and December 2012, a total of 145 GBM tumor samples were obtained from data registry. A total of 20 of the 145 patients with GBM were found to develop LMD. A specialized radiologist confirmed the diagnosis of LMD on magnetic resonance imaging. To clarify the genomic signatures in GBM with LMD, we performed integrative analysis of whole transcriptome sequencing and copy number alteration in the radiological features indicating LMD phenotypes in GBM. Eleven newly diagnosed patients with GBM with LMD had worse prognosis than those without LMD (median 5.55 vs. 12.94 months, P < 0.0001). Integrating analysis using gene expression based on the change of copy number revealed that SPOCK1, EHD2, SLC2A3, and ANXA11 were highly expressed with the gain of copy number, compared with the gene expression in the non-LMD group. In addition, it was demonstrated that NME2, TMEM100, and SIVA1 were downregulated with the loss of copy number. We also found that mesenchymal subtype accounted for 50% in LMD group, whereas mesenchymal subtype consisted of 29% in non-LMD group, even though there was no statistical significance (P = 0.06). Through this radiogenomic analysis, we suggested the possibility of finding candidate genes associated with LMD and highlighted the significance of integrating approach to clarify the molecular characteristics in LMD. PMID- 27399114 TI - A case report: The efficacy of pirfenidone in a Chinese patient with progressive systemic sclerosis-associated interstitial lung disease: A CARE-compliant article. AB - Systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) has become the leading SSc-related cause of death. Although various types of immunosuppressive therapy have been attempted for patients with SSc-ILD, no curative or effective treatment strategies for SSc-ILD have been developed. Therefore, management of patients with SSc-ILD remains a challenge. Here, we report a Chinese, female, SSc-ILD patient who was negative for Scl-70 and showed an excellent response to pirfenidone without obvious adverse effects. She had been suffered from dry cough and exertional dyspnea for 2 months. The chest computed tomography manifestation was consistent with a pattern of fibrotic nonspecific interstitial pneumonia. The pulmonary function test showed isolated impaired diffusion. After 11 weeks of administration of pirfenidone, the dry cough and dyspnea had disappeared. Both of the lung shadows and the pulmonary diffusion function were improved. Pirfenidone might be an effective option for early SSc-ILD treatment. A well-controlled clinical trial is expected in the future. PMID- 27399115 TI - Urinary N-acetyl-beta-D-glucosaminidase, an early marker of diabetic kidney disease, might reflect glucose excursion in patients with type 2 diabetes. AB - Recently, several renal tubular damage markers have gained considerable attention because of their clinical implications as sensitive and specific biomarkers for early stage diabetic kidney disease. However, little is known about the demographic and glucometabolic factors affecting levels of urinary N-acetyl-beta D-glucosaminidase (NAG), a marker of proximal tubular damage, in type 2 diabetes mellitus (T2DM).The aim of this study was to investigate the clinical relevance of urinary NAG with regard to demographic and glucometabolic parameters, as well as nephropathic parameters, by comparing the glomerulopathic marker of albuminuria.In this retrospective cross-sectional study, we enrolled a total of 592 patients with either prediabetes (N = 29) or T2DM (N = 563). Glucometabolic parameters (glucose, hemoglobin A1c, glycated albumin [GA], insulin, C-peptide, homeostasis model assessment [HOMA] of insulin resistance, HOMA-beta, postprandial C-peptide-to-glucose ratio [PCGR], and urinary glucose-to-creatinine ratio) and nephropathic parameters (urinary NAG, albumin-to-creatinine ratio [ACR], and estimated glomerular filtration rate) were measured.The levels of urinary NAG showed moderate positive correlation with the levels of urinary ACR in T2DM (r = 0.46). In correlation analysis, urinary NAG was more strongly correlated with body mass index (BMI) (r = -0.22; P < 0.001 vs. r = -0.02; P = 0.74), plasma stimulated glucose (r = 0.25; P < 0.001 vs. r = 0.08; P = 0.10), GA (r = 0.20; P < 0.001 vs. r = 0.13; P = 0.01), PCGR (r = -0.17; P = 0.001 vs. r = 0.09; P = 0.11), and HOMA-beta (r = -0.10; P = 0.05 vs. r = -0.02; P = 0.79) than urinary ACR. In multiple regression analysis, age, lower BMI, stimulated glucose, GA, and urinary ACR predicted increased urinary NAG.In conclusion, increase in urinary NAG may be related to glycemic parameters reflecting glucose fluctuation and decreased insulin secretory capacity in patients with T2DM. Further longitudinal, prospective studies are needed to investigate a causal relationship between glucose fluctuations, renal tubular damage, and other vascular complications of diabetes. PMID- 27399116 TI - The trends of utilization in traditional Chinese medicine in Taiwan from 2000 to 2010: A population-based study. AB - INTRODUCTION: There is no study exploring the trend of utilization in traditional Chinese medicine (TCM) from 2000 to 2010. The objective of this study was to investigate the trends of TCM utilization among 3 cross-sectional cohorts of 2000, 2005, and 2010. METHOD: This study was a cross-sectional analysis of TCM utilization over time. We compared the mean TCM visits among 3 cohorts of 2000, 2005, and 2010. We derived 3 randomly sampled cohorts of nearly 1 million representative beneficiaries in each of 2000, 2005, and 2010 from National Health Insurance Research Database for this research. Multivariate logistic regression was performed to evaluate the relative relationship in categorical variables correlating to TCM users. The percentage change (% change) in mean TCM visits between 2000 and 2005 (2010) was used to evaluate the trends of TCM utilization during the period. RESULTS: The ratio of TCM users increased throughout cohorts. The ratio of TCM users among women was more than that among men in all cohorts of 2000, 2005, and 2010 (adjusted odds ratio = 1.47; 1.52; 1.62). The mean TCM visits increased from 2000 to 2010. The percentage change in mean TCM visits among women was more than that among men. The group aged less than 20 years had the least percentage change in mean TCM visits (18.8%); nevertheless, the group aged 20 to 34 years had the largest change (30.2%). The high socioeconomic status group had the largest percentage change in mean visits to TCM, whereas the central region had the least percentage change. Neoplasms had the greatest increase in percentage change in mean TCM visits among all disease categories; in contrast, diseases of the respiratory system had the greatest decrease. CONCLUSION: Both the ratio of TCM users and mean TCM visits increased gradually from 2000 to 2005 and further to 2010. Women used TCM more than men, and this is expected to continue in the future. The high socioeconomic status group used TCM more and more over time. The picture of TCM need among different types of cancer patients should be explored in further research because of the substantial increase in TCM utilization for the disease category of neoplasms. PMID- 27399118 TI - Recurrent chondrosarcoma of the larynx: A case report and literature review. AB - BACKGROUND: Laryngeal chondrosarcoma (LCS) is a rare laryngeal tumor that most commonly originates from the cricoid cartilage. The current trend for treatment of low-grade LCS is function-sparing surgical option with negative margins. CASE SUMMARY: We reported here a case of a 63-year-old male patient with a 3-month history of progressive hoarseness and throat pain. The patient had undergone surgical resection of a laryngeal mass 2 years prior. A supracricoid partial laryngectomy was performed this time. Histological examination supported the diagnosis of low-grade chondrosarcoma. Three years later, the radiological and clinical findings showed no evidence of recurrence. CONCLUSION: Currently, total laryngectomy is preferred for patients with recurrent low-grade LCS. However, the literature review and our case suggest that a second function-preserving procedure may be a reasonable choice for recurrent LCS. PMID- 27399117 TI - Association between seizures after ischemic stroke and stroke outcome: A systematic review and meta-analysis. AB - A systematic review and meta-analysis were performed to investigate a potential association between post-ischemic stroke seizures (PISS) and subsequent ischemic stroke (IS) outcome.A systematic search of two electronic databases (Medline and Embase) was conducted to identify studies that explored an association between PISS and IS outcome. The primary and secondary IS outcomes of interest were mortality and disability, respectively, with the latter defined as a score of 3 to 5 on the modified Rankin Scale.A total of 15 studies that were published between 1998 and 2015 with 926,492 participants were examined. The overall mortality rates for the patients with and without PISS were 34% (95% confidence interval [CI], 27-42%) and 18% (95% CI, 12-23%), respectively. The pooled relative ratio (RR) of mortality for the patients with PISS was 1.97 (95% CI, 1.48-2.61; I = 88.6%). The overall prevalence rates of disability in the patients with and without PISS were 60% (95% CI, 32-87%) and 41% (95% CI, 25-57%), respectively. Finally, the pooled RR of disability for the patients with PISS was 1.64 (95% CI, 1.32-2.02; I = 66.1%).PISS are significantly associated with higher risks of both mortality and disability. PISS indicate poorer prognoses in patients experiencing IS. PMID- 27399119 TI - Risk factors for the effect of anticoagulant and antiplatelet agents on perioperative blood loss following proximal femoral fractures. AB - To examine the effect of oral anticoagulant and antiplatelet agents on perioperative blood loss following proximal femoral fractures and to identify the risk factors associated with perioperative blood loss.Retrospective cross sectional study.In a retrospective cross-sectional study, we treated 334 consecutive patients with proximal femoral fractures (100 who received anticoagulant or antiplatelet drugs and 234 who did not) and an overall mean age of 85.5 years (standard deviation 8.2 years). We performed retrospective multivariate analysis to determine the independent factors related to perioperative decreases in the hemoglobin (Hb) level, a proxy for blood loss.Multivariate analysis confirmed that anticoagulant or antiplatelet drugs significantly affected decreases in the Hb level (regression coefficient [RC], 0.61; 95% confidence interval [CI], 0.14-1.08; P = 0.01). In addition to anticoagulant or antiplatelet drugs, multivariate analysis confirmed that the fracture type (Orthopedic Trauma Association classification A2: RC, 1.19; 95% CI, 0.71-1.67; P < 0.01; A3: RC, 2.47; 95% CI, 1.41-3.53; P < 0.01), platelet count (RC, -0.08; 95% CI, -0.12 to -0.04; P < 0.01), and operative time (RC, 0.02; 95% CI, 0.004-0.03; P = 0.01) affected the decreases in Hb level.The use of anticoagulants and antiplatelet agents is an independent risk factor for perioperative blood loss following proximal femoral fractures. Fracture type, platelet count, and operative time also affect perioperative blood loss. The fracture type was the greatest contributing factor to perioperative blood loss.Level of evidence grade: Prognostic level III. PMID- 27399120 TI - Dietary fat intake and endometrial cancer risk: A dose response meta-analysis. AB - Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case-control studies were included. Pooled analysis of case-control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73-0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case-control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk. PMID- 27399121 TI - The effectiveness and safety of preoperative use of erythropoietin in patients scheduled for total hip or knee arthroplasty: A systematic review and meta analysis of randomized controlled trials. AB - INTRODUCTION: Because allogeneic blood transfusion carries a risk of serious complications, erythropoietin (EPO) has been used in patients scheduled for total hip or knee arthroplasty in an effort to reduce the need for allogeneic blood transfusion; however, its efficacy, cost-effectiveness, and safety are still controversial. The purpose of this review was to determine the hematopoiesis promoting effect and potential complications, as well as the cost-effectiveness, of preoperative use of EPO in patients scheduled for total hip or knee arthroplasty. METHODS: We searched MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov databases for relevant literature from 2000 to 2015. Risk of bias was assessed for all included studies and data were extracted and analyzed. RESULTS: Preoperative use of EPO was associated with lower exposure to allogeneic blood transfusion (odds ratio = 0.41) and higher hemoglobin concentration after surgery (standardized mean difference = 0.86, P < 0.001). Complications were not generally reported, but there was no significant difference between the group with and without EPO based on given data. Cost-effectiveness was also summarized but was not conclusive. CONCLUSION: Preoperative administration of EPO reduces the requirement for allogeneic blood transfusion and increases hemoglobin level after surgery. The studies of cost-effectiveness were not conclusive. Further studies and guidelines specific to blood management in the perioperative stage of total knee and hip arthroplasty are expected. PMID- 27399122 TI - Airway management in patients with deep neck infections: A retrospective analysis. AB - Securing the airway in patients undergoing surgical intervention to control a deep neck infection (DNI) is challenging for anesthesiologists due to the distorted airway anatomy, limited mouth opening, tissue edema, and immobility. It is critical to assess the risk of a potential difficult airway and prepare the most appropriate airway management method.We reviewed our anesthetic experiences managing patients with DNIs, focusing on the need for video-laryngoscope or awake fiberoptic intubation beyond a standard intubation from the anesthesiologist's perspective.When patients had infections in the masticatory space, mouth of floor, oropharyngeal mucosal space, or laryngopharynx, their airways tended to be managed using methods requiring more effort by the anesthesiologists, and more extensive equipment preparation, compared with use of a standard laryngoscope. The degree to which the main lesion influenced the airway anatomy, especially at the level of epiglottis and aryepiglottic fold was related to the airway management method selected.When managing the airways of patients undergoing surgery for DNIs under general anesthesia, anesthesiologists should use imaging with computed tomography to evaluate the preoperative airway status and a comprehensive understanding of radiological findings, comorbidities, and patients' symptoms is needed. PMID- 27399123 TI - Comparison of the diagnostic accuracy of FBP, ASiR, and MBIR reconstruction during CT angiography in the evaluation of a vessel phantom with calcified stenosis in a distal superficial femoral artery in a cadaver extremity. AB - PURPOSE: To investigate whether adaptive statistical iterative reconstruction (ASiR) or model-based iterative reconstruction (MBIR) improves the diagnostic performance of computed tomography angiography (CTA) for small-vessel calcified lesions relative to filtered back projection (FBP) using cadaver extremities and a calcified stenosis phantom. METHODS: A cadaver was used in accordance with our institutional regulations, and a calcified stenosis phantom simulating 4 grades of stenosis was prepared. The phantom was inserted within the distal superficial femoral artery of the cadaver leg. Ten CT images per reconstruction type and stenosis grade were acquired using a 64-slice multidetector-row CTA.As an objective measurement, the first and second derivatives of the CT value function profiles were calculated. As a subjective measurement, 2 blinded reviewers measured the stenosis ratio using a quantitative scale. The Wilcoxon rank-sum test was used to evaluate the data. RESULTS: Objective measurements of both 25% and 50% stenosis differed significantly (P < 0.01) between MBIR (25/50%: 25.80/50.30 +/- 3.88/3.86%) and FBP (25/50%: 35.60/83.80 +/- 3.44/26.10%), whereas significant differences were not observed between ASiR and FBP.Reviewer 2's subjective measurements of 25% stenosis differed significantly (P < 0.01) between MBIR (35.13 +/- 3.25%) and ASiR (40.89 +/- 3.14%), and the measurements of 50% stenosis differed significantly (P < 0.01) between MBIR (reviewers 1/2, 62.36/54.78 +/- 2.78/4.96%) and FBP (reviewers 1/2, 62.36/74.84 +/- 2.78/18.10%). Significant differences in the subjective measurements were not observed between ASiR and FBP. CONCLUSION: MBIR improves the diagnostic performance of CTA for small-vessel calcified lesions relative to FBP. PMID- 27399124 TI - Impact of coronary artery bypass surgery and percutaneous coronary intervention on mortality in patients with chronic kidney disease and on dialysis: A systematic review and meta-analysis. AB - Controversies have been observed among previously published and recently published studies comparing coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD) and patients on chronic dialysis. This study aimed to show the impact of CABG and PCI on mortality in these patients.Electronic databases were searched for studies comparing CABG and PCI in patients with CKD. The primary outcome was all-cause death whereas the secondary endpoints included other adverse cardiovascular outcomes reported. Causes of death were also analyzed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3.Eighteen studies involving a total number of 69,456 patients (29,239 patients in the CABG group and 40,217 patients in the PCI group) were included in this meta-analysis. Short-term mortality insignificantly favored PCI with OR: 1.24, 95% CI: 0.93-1.65; P = 0.15. Mortality at 1 year was similar in both groups with OR: 0.99, 95% CI: 0.91-1.08; P = 0.86, whereas the long-term mortality significantly favored CABG in patients with CKD and in patients on chronic dialysis with OR: 0.81, 95% CI: 0.70-0.94; P = 0.007 and OR: 0.81, 95% CI: 0.69 0.96; P = 0.01, respectively.In patients with CKD, the impact of CABG on the short-term mortality was insignificantly higher compared to PCI whereas at 1 year, a similar impact was observed. However, the impact of PCI on mortality was significantly higher during a long-term follow-up period in patients with CKD and in patients on chronic dialysis. Nevertheless, due to a high level of heterogeneity observed among several subgroups analyzed, randomized trials are required to completely solve this issue. PMID- 27399125 TI - Stent thrombosis and adverse cardiovascular outcomes observed between six months and five years with sirolimus-eluting stents and other drug-eluting stents in patients with Type 2 diabetes mellitus complicated by coronary artery disease: A systematic review and meta-analysis. AB - This study aimed to compare 6 months to 5 years stent thrombosis (ST) and adverse cardiovascular outcomes associated with sirolimus-eluting stents (SES) and other drug-eluting stents (DES) in patients with type 2 diabetes mellitus (T2DM).Electronic databases were searched for studies comparing SES with other DES in patients with T2DM. Total ST, definite ST, probable ST, and other adverse cardiovascular outcomes reported between 6 months and 5 years were considered as the clinical end points in this study. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for categorical variables and the pooled analyses were performed with RevMan 5.3 software.Twenty-nine studies involving a total number of 25,729 patients with diabetes were included in this meta-analysis. SES were not associated with significantly higher total, definite, and probable STs with OR: 0.95, 95% CI: 0.77-1.17, P = 0.62; OR: 0.94, 95% CI: 0.65-1.37, P = 0.76; and OR: 1.05, 95% CI: 0.77-1.45, P = 0.74, respectively. SES were also noninferior to the other non-sirolimus eluting drug eluting stents (non-SE DES) in terms of all-cause mortality, cardiac death, myocardial infarction, and stroke with OR: 0.92, 95% CI: 0.82-1.03, P = 0.16; OR: 1.09, 95% CI: 0.88-1.35, P = 0.44; OR: 0.92, 95% CI: 0.80-1.06, P = 0.26; and OR: 0.79, 95% CI: 0.49-1.28, P = 0.43, respectively. Target vessel revascularization, target lesion revascularization, and major adverse cardiac events were also similarly reported between SES and non-SE DES with OR: 1.04, 95% CI: 0.83-1.31, P = 0.72; OR: 1.25, 95% CI: 0.95-1.64, P = 0.11; and OR: 1.06, 95% CI: 0.90-1.25, P = 0.49, respectively.During this particular follow-up period, SES were not associated with any increase in ST among these patients with T2DM. Mortality and other adverse cardiovascular outcomes were also not significantly different between these 2 groups. Hence, SES should be considered neither superior nor inferior to other DES. They are expected to be equally effective and safe to use in patients with T2DM. PMID- 27399126 TI - mRNA expression of CDH3, IGF2BP3, and BIRC5 in biliary brush cytology specimens is a useful adjunctive tool of cytology for the diagnosis of malignant biliary stricture. AB - Although advances have been made in diagnostic tools, the distinction between malignant and benign biliary strictures still remains challenging. Intraductal brush cytology is a convenient and safe method that is used for the diagnosis of biliary stricture, but, low sensitivity limits its usefulness. This study aimed to demonstrate the usefulness of mRNA expression levels of target genes in brush cytology specimens combined with cytology for the diagnosis of malignant biliary stricture. Immunohistochemistry for cadherin 3 (CDH3), p53, insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3), homeobox B7 (HOXB7), and baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) was performed in 4 benign and 4 malignant bile duct tissues. Through endoscopic or interventional radiologic procedures, brush cytology specimens were prospectively obtained in 21 and 35 paitents with biliary strictures. In the brush cytology specimens, the mRNA expressions levels of 5 genes were determined by real-time polymerase chain reaction. Immunohistochemistry for CDH3, p53, IGF2BP3, HOXB7, and BIRC5 all showed positive staining in malignant tissues in contrast to benign tissues, which were negative. In the brush cytology specimens, the mRNA expression levels of CDH3, IGF2BP3, HOXB7, and BIRC5 were significantly higher in cases of malignant biliary stricture compared with cases of benign stricture (P = 0.006, P < 0.001, P < 0.001, and P = 0.001). The receiver-operating characteristic curves of these 4 mRNAs demonstrated that mRNA expression levels are useful for the prediction of malignant biliary stricture (P = 0.006, P < 0.001, P < 0.001, and P = 0.002). The sensitivity and specificity, respectively, for malignant biliary stricture were 57.1% and 100% for cytology, 57.1% and 64.3% for CDH3, 76.2% and 100% for IGF2BP3, 71.4% and 57.1% for HOXB7, and 76.2% and 64.3% for BIRC5. When cytology was combined with the mRNA levels of CDH3, IGF2BP3, or BIRC5, the sensitivity for malignant biliary stricture improved to 90.5%. The measurement of the mRNA expression levels of CDH3, IGF2BP3, and BIRC5 by real-time polymerase chain reaction combined with cytology was useful for the differentiation of malignant and benign biliary strictures in brush cytology specimens. PMID- 27399127 TI - Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients. AB - Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients. PMID- 27399128 TI - Low serum 25-hydroxyvitamin D level and risk of urinary tract infection in infants. AB - The aim of the study is to determine whether serum 25-hydroxyvitamin D (25(OH)D) deficiency in infants increased odds of urinary tract infection (UTI). A total of 238 infants including 132 patients experiencing a first episode of UTI and 106 controls, aged from 1 to 12 months, were enrolled. Serum 25(OH)D levels were tested through blood sampling. The serum 25(OH)D levels were significantly lower in cases with UTI than controls. The mean serum 25(OH)D levels were 29.09 +/- 9.56 ng/mL in UTIs and 38.59 +/- 12.41 ng/mL in controls (P < 0.001). Infants with acute pyelonephritis (APN) had lower serum 25(OH)D than those with lower UTI. The multivariate logistic regression analyses showed that serum 25(OH)D < 20 ng/mL (OR 5.619, 95% CI 1.469-21.484, P = 0.012) was positively related to an increased odds of UTI. Vitamin D supplementation (OR 0.298, 95% CI 0.150-0.591; P = 0.001) was associated with a decreased likelihood of UTI. Vitamin D deficiency in infants was associated with an increased odds of UTI. Interventional studies evaluating the role of vitamin D supplementation to reduce the burden of UTI are warranted. PMID- 27399129 TI - The effect of individual and neighborhood socioeconomic status on esophageal cancer survival in working-age patients in Taiwan. AB - Esophageal cancer is the sixth leading cause of cancer mortality. More than 90% of patients with esophageal cancer in Taiwan have squamous cell carcinoma. Survival of such patients is related to socioeconomic status (SES). We studied the association between SES (individual and neighborhood) and the survival of working-age patients with esophageal cancer in Taiwan. A population-based study was conducted of 4097 patients diagnosed with esophageal cancer between 2002 and 2006. Each was traced for 5 years or until death. Individual SES was defined by enrollee job category. Neighborhood SES was based on household income and dichotomized into advantaged or disadvantaged. Multilevel logistic regression was used to compare the survival rates by SES group after adjustment for possible confounding and risk factors. Hospital and neighborhood SES were used as random effects in multilevel logistic regression. In patients younger than 65 years, 5 year overall survival rates were worst for those with low individual SES living in disadvantaged neighborhoods. After adjustment for patient characteristics, esophageal cancer patients with high individual SES had a 39% lower risk of mortality than those with low individual SES (odds ratio 0.61, 95% confidence interval 0.48-0.77). Patients living in disadvantaged areas with high individual SES were more likely to receive surgery than those with low SES (odds ratio 1.45, 95% confidence interval 1.11-1.89). Esophageal cancer patients with low individual SES have the worst 5-year survival, even with a universal healthcare system. Public health, education, and social welfare programs should address the inequality of esophageal cancer survival. PMID- 27399130 TI - Can orthopedic surgeons help create a better head start for osteoporosis treatment after hip fracture? AB - BACKGROUND: Treatment for osteoporosis in the community in patients who were operated for hip fracture appears to be suboptimal at best. Evidence regarding treatment beyond the 1st year after surgery is scarce. We examined the association between discharge recommendations for treatment of osteoporosis in patients suffering from hip fractures and treatment beyond the 1st year. METHODS AND MATERIALS: We performed a retrospective observational cohort study in patients age 50 to 90 years operated for osteoporotic hip fractures between the years 2008 and 2014. We investigated the correlation between discharge recommendations and rates of osteoporosis treatment postdischarge 1 to 7 years, and the influence of osteoporosis diagnosis upon treatment. Exclusion criteria besides age included high-energy trauma, pathologic or periprosthetic fractures, and patients deceased within 1-year postsurgery. RESULTS: A total of 602 patient files were examined. Univariate analysis showed that, of 283 patients who were prescribed dietary supplementation of vitamin D and calcium, a significantly higher percentage of patients received treatment if they had a recommendation (50.3% vs 36.1%, P = 0.0005), were diagnosed (43.8% vs 14.4%, P < 0.0001), or were of female gender (84.1% vs 57.3%, P < 0.0001). Multivariate analysis showed that the odds ratio (OR) for receiving treatment compared with the control group (patients without a recommendation and a diagnosis) was higher among patients who had both a recommendation and a treatment (OR = 5.4, P < 0.0001) than the group with a diagnosis only (OR = 4.75, P < 0.0001) or a recommendation only (OR = 2.06, P = 0.0006). CONCLUSIONS: A formal recommendation for osteoporosis treatment in the discharge letters of patients who suffered hip fragility fractures increases treatment rate of osteoporosis in the community compared with patients without a recommendation. Patients who receive such a recommendation but also have a formal coded diagnosis of osteoporosis in their medical files have an even higher chance of receiving treatment in the community. Our observations may assist in amplifying the overall treatment rates, which are still undoubtedly low. PMID- 27399131 TI - The effect of a dual or a triple antithrombotic therapy with apixaban on thrombus formation in vivo and in an ex vivo perfusion chamber model: An open-label, controlled, sequential study. AB - BACKGROUND: There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber. METHODS AND RESULTS: Shed blood platelet activation (beta thromboglobulin [beta-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open label, parallel group trial in 40 healthy male volunteers (n = 20 per group). Subjects received ticagrelor and apixaban without or with acetylsalicylic acid (ASA). Outcome parameters were assessed at 3 hours after therapy dosing, and at steady-state trough and peak conditions.A triple or dual therapy induced a comparable decrease in shed blood beta-TG at 3 hours after therapy dosing but was more pronounced at steady-state conditions with the more intense treatment combination. During both antithrombotic regimens a similarly sustained inhibition in thrombin generation was observed which was accompanied by comparable increases in shed blood volume. In contrast, no treatment effect could be observed in the perfusion chamber experiment. CONCLUSION: Ticagrelor and apixaban with or without ASA inhibit platelet activation and thrombin formation in vivo in healthy subjects. Platelet inhibition was greater at steady-state conditions after triple therapy administration. PMID- 27399132 TI - Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease: A PRISMA-compliant systematic review and meta-analysis. AB - BACKGROUND/AIMS: Several neuropathological, biochemical, and pharmacological data suggested a possible role of histamine in the etiopathogenesis of Parkinson disease (PD). The single nucleotide polymorphism (SNP) rs11558538 in the histamine N-methyltransferase (HNMT) gene has been associated with the risk of developing PD by several studies but not by some others. We carried out a systematic review that included all the studies published on PD risk related to the rs11558538 SNP, and we conducted a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: We used several databases to perform the systematic review, the software Meta-DiSc 1.1.1 to perform the meta-analysis of the eligible studies, and the Q-statistic to test heterogeneity between studies. RESULTS: The meta-analysis included 4 eligible case-control association studies for the HNMT rs11558538 SNP and the risk for PD (2108 patients, 2158 controls). The frequency of the minor allele positivity showed a statistically significant association with a decreased risk for PD, both in the total series and in Caucasians. Although homozygosity for the minor allele did not reach statistical significance, the test for trend indicates the occurrence of a gene-dose effect. Global diagnostic odds ratios (95% confidence intervals) for rs11558538T were 0.61 (0.46-0.81) for the total group, and 0.63 (0.45-0.88) for Caucasian patients. CONCLUSION: The present meta analysis confirms published evidence suggesting that the HNMT rs11558538 minor allele is related to a reduced risk of developing PD. PMID- 27399133 TI - Integrative medicine for chronic pain: A cohort study using a process-outcome design in the context of a department for internal and integrative medicine. AB - INTRODUCTION: Integrative medicine inpatient treatment has been shown to improve physical and mental health in patients with internal medicine conditions. The aim of this study was to investigate the effectiveness of a 2-week integrative medicine inpatient treatment in patients with chronic pain syndromes and the association of treatment success with patient-related process variables. METHODS: Inpatients with chronic pain syndromes participating in a 2-week integrative medicine inpatient program were included. Patients' pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were measured on admission, discharge, and 6 months after discharge. Likewise process variables including ability and will to change, emotional/rational disease acceptance, mindfulness, life and health satisfaction, and easiness of life were assessed. RESULTS: A total of 310 inpatients (91% female, mean age 50.7 +/- 12.4 year, 26.5% low back pain, and 22.9% fibromyalgia) were included. Using mixed linear models, significant improvements in pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were found (all P < 0.05). Ability to change and implementation, disease acceptance, mindfulness, life and health satisfaction, and light heartedness/easiness likewise improved (all P < 0.05). Improved outcomes were associated with increases in process variables, mainly ability to change and implementation, disease acceptance, life and health satisfaction, and light heartedness/easiness (R = 0.03-0.40). CONCLUSIONS: Results of this study suggest that a 2-week integrative medicine inpatient treatment can benefit patients with chronic pain conditions. Functional improvements are associated with improved ability to change and implementation, disease acceptance, and satisfaction. PMID- 27399134 TI - Lung ultrasound and chest x-ray for detecting pneumonia in an acute geriatric ward. AB - BACKGROUND: Our aim was to compare the accuracy of lung ultrasound (LUS) and standard chest x-ray (CXR) for diagnosing pneumonia in older patients with acute respiratory symptoms (dyspnea, cough, hemoptysis, and atypical chest pain) admitted to an acute-care geriatric ward. METHODS: We enrolled 169 (80 M, 89 F) multimorbid patients aged 83.0 +/- 9.2 years from January 1 to October 31, 2015. Each participant underwent CXR and bedside LUS within 6 hours from ward admission. LUS was performed by skilled clinicians, blinded to CXR results and clinical history. The final diagnosis (pneumonia vs no-pneumonia) was established by another clinician reviewing clinical and laboratory data independent of LUS results and possibly prescribing chest contrast-enhanced CT. Diagnostic parameters of CXR and LUS were compared with McNemar test on the whole cohort and after stratification for Rockwood Clinical Frailty Scale. RESULTS: Diagnostic accuracy for pneumonia (96 patients) was significantly higher in LUS (0.90, 95% confidence interval [CI] 0.83-0.96) compared with CXR (0.67, 95%CI 0.60-0.74, P < 0.001). LUS had a better sensitivity (0.92, 95%CI 0.86-0.97 vs 0.47, 95%CI 0.37 0.57) and negative predictive value (0.95, 95% CI 0.83-0.96 vs 0.57, 95%CI 0.48 0.56). In those patients with frailty (n = 87 with Rockwood Clinical Frailty Scale >=5), LUS maintained a high diagnostic accuracy, but CXR did not (P = 0.0003). Interobserver agreement for LUS, calculated in a subsample of 29 patients, was high (k = 0.90). CONCLUSIONS: In multimorbid patients admitted to an acute geriatric ward, LUS was more accurate than CXR for the diagnosis of pneumonia, particularly in those with frailty. A wider use of LUS should be implemented in this setting. PMID- 27399135 TI - Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy. AB - Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979 1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication. PMID- 27399136 TI - Anterior approach combined with infrahepatic inferior vena cava clamping right hepatic resection for large hepatocellular carcinoma: A prospective randomized controlled trial. AB - BACKGROUND: The anterior approach (AA) technique has been reported to provide better operative and survival outcomes compared with the conventional approach for large right hepatocellular carcinoma (HCC) resection. However, this technique runs the risk of massive retrograde bleeding from the right hepatic vein or middle hepatic vein at the deeper plane of parenchymal transection. This study was designed to evaluate the efficacy of AA combined with infrahepatic inferior vena cava (IVC) clamping on the perioperative outcomes in patients undergoing right hepatic resection for large HCC in randomized clinical trial settings. METHODS: A total of 101 patients undergoing right hepatic resection for large HCC were randomized to receive AA combined with infrahepatic IVC clamping (group A, n = 50), or AA alone (group B, n = 51). RESULTS: The total blood loss (423 +/- 154 vs 757 +/- 338 mL; P = 0.001), blood loss during liver transection (272 +/- 96 vs 563 +/- 144 mL; P = 0.001), and intraoperative blood transfusion requirements (12.0% vs 29.4%; P = 0.031) were significantly less in group A patients compared with group B patients. There was no IVC clamping-associated morbidity in group A. CONCLUSION: AA combined with infrahepatic IVC clamping for large right HCC resection is a safe, feasible, and effective technique in reducing intraoperative blood loss. PMID- 27399137 TI - Relationship between indexed epicardial fat volume and coronary plaque volume assessed by cardiac multidetector CT. AB - We explored whether baseline indexed epicardial fat volume (EFVi) and serial changes in EFVi were associated with increase in coronary plaque volume as assessed by multidetector computed tomography.We retrospectively reviewed 87 patients with coronary artery plaque, identified during either baseline or follow up cardiac computed tomography (CT) examinations. Each plaque volume was measured in volumetric units using a semiautomatic software tool. EFVi was quantified by calculating the total volume of epicardial tissue of CT density -190 to -30 HU, indexed to the body surface area. Clinical cardiovascular risk factors were extracted by medical record review at the time of the cardiac CT examinations. The relationship between EFVi and coronary plaque volume was explored by regression analysis.Although the EFVi did not change significantly from baseline to the time of the follow-up CT (65.7 +/- 21.8 vs 66.0 +/- 21.8 cm/m, P = 0.620), the plaque volumes were increased significantly on the follow-up CT scans. The annual change in EFVi was not accompanied by a parallel change in coronary plaque volume (P = 0.096-0.500). On univariate analysis, smoking, hypercholesterolemia, 10-year coronary heart disease risk, obesity, and baseline EFVi predicted rapid increases in lipid-rich and fibrous plaque volumes. On multivariate analysis, baseline EFVi (odds ratio = 1.029, P = 0.016) was an independent predictor of a rapid increase in lipid-rich plaque volume.EFVi was shown to be an independent predictor of a rapid increase in lipid-rich plaque volume. However, changes in EFVi were not associated with parallel changes in coronary plaque volume. PMID- 27399138 TI - A case report of severely damaged hip joint caused by SAPHO syndrome treated with 2-stage total hip arthroplasty. AB - INTRODUCTION: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an increasingly recognized entity. The hip joint is known as a less frequently affected site in SAPHO syndrome, and there has been limited reports about hip joint diseases caused by SAPHO syndrome, and as such adequate treatment for this disease spectrum is still not fully elucidated. CASE: We describe the case of a 52-year-old man admitted for SAPHO syndrome who went on to be diagnosed with advanced secondary hip arthritis associated with disabling right hip pain. The diagnosis of SAPHO syndrome was delayed; the patient was given a clinical diagnosis of osteomyelitis and treated with prolonged courses of antibiotics and open surgical debridement at previous tertiary health facility. The patient underwent 2-stage joint replacement surgery in our hospital. At 1 year after the surgery, he is well, with minimal right hip pain and the prosthesis is functioning well. CONCLUSION: This case shows the safety and effectiveness of the 2-stage joint replacement in treating destructive hip disease caused by SAPHO syndrome mimicking infectious arthritis. PMID- 27399139 TI - Quantitative single-photon emission computed tomography/computed tomography for technetium pertechnetate thyroid uptake measurement. AB - OBJECTIVES: Technetium pertechnetate (TcO4) is a radioactive tracer used to assess thyroid function by thyroid uptake system (TUS). However, the TUS often fails to deliver accurate measurements of the percent of thyroid uptake (%thyroid uptake) of TcO4. Here, we investigated the usefulness of quantitative single photon emission computed tomography/computed tomography (SPECT/CT) after injection of TcO4 in detecting thyroid function abnormalities. MATERIALS AND METHODS: We retrospectively reviewed data from 50 patients (male:female = 15:35; age, 46.2 +/- 16.3 years; 17 Graves disease, 13 thyroiditis, and 20 euthyroid). All patients underwent TcO4 quantitative SPECT/CT (185 MBq = 5 mCi), which yielded %thyroid uptake and standardized uptake value (SUV). Twenty-one (10 Graves disease and 11 thyroiditis) of the 50 patients also underwent conventional %thyroid uptake measurements using a TUS. RESULTS: Quantitative SPECT/CT parameters (%thyroid uptake, SUVmean, and SUVmax) were the highest in Graves disease, second highest in euthyroid, and lowest in thyroiditis (P < 0.0001, Kruskal-Wallis test). TUS significantly overestimated the %thyroid uptake compared with SPECT/CT (P < 0.0001, paired t test) because other TcO4 sources in addition to thyroid, such as salivary glands and saliva, contributed to the %thyroid uptake result by TUS, whereas %thyroid uptake, SUVmean and SUVmax from the SPECT/CT were associated with the functional status of thyroid. CONCLUSIONS: Quantitative SPECT/CT is more accurate than conventional TUS for measuring TcO4 %thyroid uptake. Quantitative measurements using SPECT/CT may facilitate more accurate assessment of thyroid tracer uptake. PMID- 27399141 TI - Treatment of mites folliculitis with an ornidazole-based sequential therapy: A randomized trial. AB - OBJECTIVE: Treatment of Demodex infestations is often inadequate and associated with low effective rate. We sought to evaluate the efficacy of an ornidazole based sequential therapy for mites folliculitis treatment. METHODS: Two-hundred patients with mites folliculitis were sequentially treated with either an ornidazole- or metronidazole-based regimen. Sebum cutaneum was extruded from the sebaceous glands of each patient's nose and the presence of Demodex mites were examined by light microscopy. The clinical manifestations of relapse of mites folliculitis were recorded and the subjects were followed up at 2, 4, 8, and 12 weeks post-treatment. RESULTS: Patients treated with the ornidazole-based regimen showed an overall effective rate of 94.0%. Additionally, at the 2, 4, 8, and 12 week follow-up, these patients had significantly lower rates of Demodex mite relapse and new lesion occurrence compared with patients treated with the metronidazole-based regimen (P < 0.05). CONCLUSION: Sequential therapy using ornidazole, betamethasone, and recombinant bovine basic fibroblast growth factor (rbFGF) gel is highly effective for treating mites folliculitis. PMID- 27399142 TI - Neo-digit functional reconstruction of mutilating hand injury using transplantation of multiple composite tissue flaps. AB - PURPOSE: Functional reconstruction of mutilating hand injuries poses a challenge to the surgeon. We present our experience with use of multiple composite tissue flaps transplant for functional reconstruction of hand in patients with mutilating hand injuries. The associated merits and demerits of these surgical approaches are briefly discussed. METHODS: From August 2004 to October 2014, functional reconstruction of hand with transplantation of multiple composite tissue flaps was performed in 8 patients. These included the toe with dorsal pedis artery flap, the reverse posterior interosseous artery flap, and the anterolateral thigh flap. Mean interval from injury to functional reconstruction was 10.6 days. RESULTS: All transplanted skin flaps and reconstructed neofingers survived completely. Only 1 patient developed wound infection at the recipient site (hand), which resolved without any debridement or revision surgery. At the donor site (foot), partial skin necrosis was observed in 1 patient, which healed with local wound care. In other patients, all wounds healed without any complications. The average range of movement at the neofinger metacarpophalangeal and interphalangeal joints was 38 degrees and 73 degrees , respectively. None of the patients required revision surgery. CONCLUSION: Use of negative pressure wound therapy and multiple composite tissue flap transplantation appears to be an effective strategy for hand functional reconstruction in patients with mutilating hand injuries. Among the multiple composite tissue flaps, use of toe transplantation combined with reverse posterior interosseous artery flap appears to be the best option. PMID- 27399140 TI - Prevalence of adjacent segment disease following cervical spine surgery: A PRISMA compliant systematic review and meta-analysis. AB - Prevalence estimates of adjacent segment degeneration (ASD) following cervical spine surgery varied greatly in current studies. We conducted a systematic review and meta-analysis to summarize the point prevalence of ASD after cervical spine surgery. METHODS: Comprehensive electronic searches of PubMed, Embase, Web of Knowledge, and Cochrane Library databases were conducted to identify any study published from initial state to January 2016. Those reporting the prevalence of ASD after cervical surgery were included. A random-effects model was used to estimate the prevalence of radiographic ASD, symptomatic ASD, and reoperation ASD. Univariate meta-regression analyses were conducted to explore the potential associations between prevalence and length of follow-up. All analyses were performed using R version 3.2.3 (R Foundation for Statistical Computing). RESULTS: A total of 83 studies were included in the meta-analysis. The prevalence of radiographic ASD, symptomatic ASD, and reoperation ASD after cervical surgery was 28.28% (95% confidence interval [CI], 20.96-36.96), 13.34% (95% CI, 11.06 16.00), and 5.78% (95% CI, 4.99-6.69), respectively, in a general analysis. It was found 2.79%, 1.43%, and 0.24% additions per year of follow-up in the incidence of radiographic ASD, symptomatic ASD, and reoperation ASD, respectively. CONCLUSION: This meta-analysis provides some details about the prevalence of radiographic ASD, symptomatic ASD, and reoperation ASD after cervical spine surgery. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among the studies. PMID- 27399143 TI - Cutaneous mucormycosis postcosmetic surgery: A case report and review of the literature. AB - BACKGROUND: Mucormycosis is a rare, aggressive, and life-threatening infection that is caused by organisms belonging to the order Mucorales. It is usually acquired through direct means and virtually always affects immunocompromised patients with the port of entry reflecting the site of infection, in this case, cutaneous. Unlike other mucormycoses, patients affected by Apophysomyces elegans (A elegans) are known to be immunocompetent. This locally aggressive disease penetrates through different tissue plains invading adjacent muscles, fascia, and even bone causing extensive morbidity and may prove fatal if treated inadequately. Cutaneous mucormycosis is associated with disruption of cutaneous barriers such as trauma. However, rarely, it may be iatrogenic. No cases have been previously reported postcosmetic surgery, especially one that is so commonly performed, lipofilling. CASE REPORT: The patient is a, previously healthy, 41 year-old middle-eastern female who was admitted to the plastic surgery department 17 days after undergoing cosmetic surgery. She suffered from extensive tissue inflammation and necrosis in both gluteal regions. Following admission, she was initially started on empirical antimicrobial therapy which was changed to an antifungal agent, voriconazole, when preliminary microbiological results showed filamentous fungi. This was discontinued and liposomal amphotericin B was commenced when further mycological analysis identified A elegans. Furthermore, she underwent a total of 10 sessions of extensive debridement to the extent that portions of the sacrum and left femoral head became exposed. Her clinical status and wounds improved with the appropriate management and she remained an inpatient for 62 days. Subsequently, she had defects in both gluteal regions which required reconstructive surgery. CONCLUSION: A elegans is an uncommon cause of iatrogenic cutaneous mucormycosis. A high index of clinical suspicion is required, especially in the absence of clinical improvement despite conventional methods of treatment, so that early diagnosis can be reached and the appropriate management instigated promptly in order to mitigate morbidity and mortality. Reversal of predisposing risk factors, regular extensive surgical debridement, and antifungal therapy remain the cornerstones of therapy for this life-threatening condition. PMID- 27399144 TI - Impact of pay-for-performance on mortality in diabetes patients in Taiwan: A population-based study. AB - BACKGROUND: The impact of pay-for-performance (P4P) programs on long-term mortality for chronic illnesses, especially diabetes mellitus, has been rarely reported. Several studies described the favorable impact of P4P for diabetes mellitus on medical utilizations or intermediate outcomes. Therefore, this study aimed to investigate the impact of a P4P program on mortality in patients with type 2 diabetes. METHODS: The P4P group in this population-based cohort study was 2090 individuals with a primary diagnosis of type 2 diabetes who had been newly enrolled in the P4P program of Taiwan between January 1, 2004 and December 31, 2004. Matched by 1:1 ratio, patients in the non-P4P group were selected by propensity score matching (PSM) for sex, age, the first year of diagnosis as diabetes, and 32 other potential confounding factors. Mean (SD) age was 60.91 (12.04) years when diabetes was first diagnosed and mean (SD) duration of diabetes was 4.3 (1.9) years at baseline. The time-dependent Cox regression model was used to explore the impact of P4P on all-cause mortality. RESULTS: During a mean of 5.13 years (SD = 1.07 years) of follow-up, 206 and 263 subjects died in the P4P group and the non-P4P group, respectively. After adjusting for the potential confounding factors at baseline, survival was significantly longer in the P4P group than in the non-P4P group (hazard ratio, 0.76 [95% confidence interval, 0.64-0.92], P = 0.004, by log-rank test). This decrease in mortality is equivalent to one less death for every 37 patients who were treated in the P4P program for 5.13 years. In this study, the P4P program significantly increased the medical utilization of physician visits and diabetes-related examinations, improved the adherence of oral hypoglycemic drugs during the first 3 years and that of insulin during the second 3 years, and was negatively associated with risk of cancer and chronic kidney disease. In annual health expense, there was no significant difference between P4P and non-P4P groups, P = 0.430. CONCLUSIONS: As compared with control, pay-for-performance program significantly improved survival in patients with diabetes without increasing the medical cost. The P4P group had significantly lower risk of cancer and chronic kidney disease. PMID- 27399145 TI - Thermodynamic selectivity of functional agents on zeolite for sodium dodecyl sulfate sequestration. AB - This study proposes a thermodynamic approach to effectively select functional agents onto zeolite for sodium dodecyl sulfate (SDS) sequestration in greywater reuse. We combine isothermal titration calorimetry (ITC) and quantum chemistry simulation (QCS) to identify the interactions between SDS and agents at the molecular level. Three potential agents, cetyl trimethyl ammonium bromide (CTAB), N,N,N-trimethyltetradecan-1-aminium bromide (C14TAB), and 14-hydroxy-N,N,N trimethyltetradecan-1-aminium bromide (C14HTAB), differ in carbon chain length and hydrophilic groups. The ITC titration of SDS with CTAB released the highest heat, followed by those with C14TAB and C14HTAB, as was the same trend for the amounts of SDS adsorbed by the respective functionalized-zeolites. Results suggest that the favorable SDS sorption occurred at the bilayer CTAB-zeolite is driven by enthalpy as similar as the SDS...CTAB interaction found, regardless of the contribution from electrostatic and/or hydrophobic behaviors, while the declined sorption is entropy-driven via the predominant hydrophobic interaction onto the monolayer CTAB-zeolite. The data presented here interpret the nature of molecularly thermodynamic quantities and enable the manipulation of sorption capacity optimization. PMID- 27399146 TI - Selective extraction of heavy metals from two real calcium-rich contaminated soils by a modified NTA. AB - The objective of this work is to evaluate the selectivity and solubility of a buffer chelant. The buffer chelant is ethylenediamine-nitrilotriacetic acid (NTA.3EDA) and its performance is compared to NTA. All experiments were conducted on batches of 25g of soil in an autoclave at 25 degrees C or 75 degrees C with a constant L:S ratio of 2. The experiments were conducted under a CO2 overhead to lower the reaction pH. The buffer chelant allows a 5-fold selectivity increase for heavy metals while increasing or maintaining the same molar extraction yield compared to NTA. These selectivity and extraction results stand out from those obtained with other neutralized NTA. NTA, EDA and the acid gas CO2 are the three necessary ligands in the NTA.3EDA extraction mechanism. A reaction temperature setpoint increase causes a higher Fe dissolution. However, this does not lower the NTA and NTA.3EDA selectivity for heavy metals. Thus, Fe is a non-interfering cation in the NTA and NTA.3EDA extraction mechanisms. This non-interference is less apparent in the NTA extraction mechanism. The present work intends to share another perspective on the design of more selective and soluble chelants for heavy metal extraction. PMID- 27399147 TI - Anomalous but massive removal of two organic dye pollutants simultaneously. AB - A one-pot method to remove two organic dye contaminants and alkali simultaneously from alkaline wastewater was developed by forming Zn-Al layered double hydroxide (ZnAl-LDH). Using this process, not only alkali but also methyl orange (MO), an anionic contaminant was totally removed from wastewater. In addition, cationic contaminant, methylene blue (MB) was also removed effectively while maintaining the high removal efficiency of MO. The removal efficiency of MO was almost 100% and the pH of the treated wastewater decreased from 12 to 7.38. The charge limited removal process, molecular arrangement of the contaminants in LDHs, and the anomalous removal mechanism were analyzed experimentally and through simulation. After MO accumulated in the interlayers of LDH by electrostatic interaction, MB entered and trapped by hydrophobic interaction. PMID- 27399149 TI - Co-disposal of MSWI fly ash and Bayer red mud using an one-part geopolymeric system. AB - In this research, Bayer red mud (RM) was pretreated through alkali-thermal activation process, and prepared as an one-part geopolymer precursor, which could be used as geopolymeric solidification/stabilization (S/S) reagent for municipal solid waste incineration fly ash (MSWI FA). Compressive strength test, modified TCLP leaching test and sequential extraction test were conducted to evaluate the effectiveness of the RM-based geopolymeric S/S reagent. The results show that the S/S effects for heavy metals of RM-based geopolymer exhibit the following order: Pb>Cu>Zn>Cr. Most of the Zn, Pb and Cu in the MSWI FA transform from the leachable fractions into the inactive fractions difficult or unavailable to leach out. In the geopolymeric S/S solid, the active aluminosilicates in MSWI FA are dissolved in the alkaline environment formed by pretreated RM and then participate in the geopolymerization, which increases the SiO2/Al2O3 ratio and enhances the structural stability of geopolymeric S/S solid. MSWI FA offsets the strength deterioration of RM based one-part geopolymer and improves the immobilization efficiency for heavy metals in the geopolymer structure. PMID- 27399148 TI - Acute toxicity of quantum dots on late pregnancy mice: Effects of nanoscale size and surface coating. AB - In this study, the effects of cadmium containing QDs (such as CdSe/ZnS and CdSe QDs) and bulk CdCl2 in pregnant mice, their fetuses, and the pregnancy outcomes were investigated. It was shown that although the QDs and bulk CdCl2 were effectively blocked by the placental barrier, the damage on the placenta caused by CdSe QDs still led to fetus malformation, while the mice in CdSe/ZnS QDs treatment group exhibited slightly hampered growth but showed no significant abnormalities. Moreover, the Cd contents in the placenta and the uterus of CdSe QDs and CdSe/ZnS QDs treatment groups showed significantly higher than the CdCl2 treated group which indicated that the nanoscale size of the QDs allowed relative ease of entry into the gestation tissues. In addition, the CdSe QDs more effectively altered the expression levels of susceptive genes related to cell apoptosis, dysplasia, metal transport, cryptorrhea, and oxidative stress, etc. These findings suggested that the nanoscale size of the QDs were probably more important than the free Cd in inducing toxicity. Furthermore, the results indicated that the outer surface shell coating played a protective role in the adverse effects of QDs on late pregnancy mice. PMID- 27399150 TI - Poly(styrenesulfonic acid)-impregnated alginate capsule for the selective sorption of Pd(II) from a Pt(IV)-Pd(II) binary solution. AB - Poly(styrenesulfonic acid)-impregnated alginate capsule (PSSA-AC) was prepared using a simple fabrication process, and used for selective separation of Pd(II) and Pt(IV) from their mixture. Evaluation of the pH effect revealed that PSSA-AC had good Pd(II) selectivity especially when the pH was between 3 and 5 at which neutral species Pd(OH)2 are present. Experiments on metal penetration through the Ca(2+)-alginate film showed that anionic species hardly penetrate through the alginate film (acting as an ionic barrier). The selective sorption mechanism is proposed as the following steps: (1) selective penetration of the neutral Pd(OH)2 through the ionic barrier (Ca(2+)-alginate shell) and then (2) chelation reaction of the neutral Pd(OH)2 with the SO3(-) groups of PSSA in the core. The maximum Pd(II) uptake was 291.19+/-17.48mg/g, which was about 32 times higher than that of Pt(IV). The results of the sorption/desorption test indicated that the PSSA-AC has good reusability potential. Even through one cycle of sorption/desorption, Pd(II) and Pt(IV) were successfully separated from their mixture with significantly high purities of 98.65% Pd(II) and 98.71% Pt(IV). This study reports for the first time the feasibility and potential of ionic barrier-based sorbents as selective separation of precious metals which have different speciations. PMID- 27399151 TI - Clarifying the associations between individual differences in general attachment styles and psychopathy. AB - The association between individual differences in general attachment styles and psychopathy is currently unclear, despite the potential utility attachment theory could provide regarding the interpersonal characteristics of psychopathy and the etiology of this construct. The purpose of the current investigation was to clarify these associations. For this purpose, we analyzed responses from an Australian community sample (N = 249) and a U.S. community sample (N = 292) containing validated measures of psychopathy (Triarchic Psychopathy Measure and Expanded-Levenson Self-Report Psychopathy Scales [Australian sample only]) and general attachment styles (Experiences in Close Relationships-Revised-General Short Form and Attachment Styles Questionnaire) to replicate our findings across measures and samples. The psychopathy domain of boldness was consistently negatively associated with insecure attachment styles. Psychopathy's affective domain (meanness, callousness) was consistently associated with avoidant attachment, whereas its behavioral domain (disinhibition, antisocial) was consistently associated with insecure attachment styles, particularly anxious attachment. Our findings suggest that there are consistent associations between individual differences in general attachment styles and psychopathy in adult samples and provides preliminary support for further consideration of attachment theory in psychopathy research. (PsycINFO Database Record PMID- 27399152 TI - Emission properties and Cu(i)-Cu(i) interaction in 2-coordinate dicopper(i)-bis(N heterocyclic)carbene complexes. AB - The synthesis, characterization, and emission properties of 2-coordinate dicopper(i) complexes bearing two trimethylene-bridged bis-NHC ligands, [Cu2(L3Me)2](PF6)2 (1), [Cu2(L3Et)2](PF6)2 (2), [Cu2(L3Bu)2](PF6)2 (3), [Cu2(L3MeOPh)2](PF6)2 (4) and [Cu2(L3Mes)2](PF6)2 (5), where L3R denotes trimethylene-bridged bis(N-heterocyclic)carbene (NHC) ligand substituted by two R groups at the nitrogen atoms of NHC, have been investigated. The quantum yield, Phi, and the lifetime, tau, of the emission of 2, are 0.21 and 25 MUs, respectively in methanol, which is a well-known solvent for quenching the luminescence of many copper(i) complexes. The 8-shaped geometry of the dicopper(i) complexes brings a considerable copper(i)-copper(i) interaction which affects the luminescent properties. Additionally, we find that methoxyphenyl and mesityl groups substituted at the nitrogen atom of the NHC moiety drastically stabilize the bis(NHC) copper(i) complexes even in air-saturated acetone-d6. PMID- 27399153 TI - Rapid and Label-Free Strategy to Isolate Aptamers for Metal Ions. AB - Generating aptamers that bind to specific metal ions is challenging because existing aptamer discovery methods typically require chemical labels or modifications that can alter the structure and properties of the ions. In this work, we report an aptamer discovery method that enables us to generate high quality structure-switching aptamers (SSAs) that undergo a conformational change upon binding a metal ion target, without the requirement of labels or chemical modifications. Our method is more efficient than conventional selection methods because it enables direct measurement of target binding via fluorescence activated cell sorting (FACS), isolating only the desired aptamers with the highest affinity. Using this strategy, we obtained a highly specific DNA SSA with ~30-fold higher affinity than the best aptamer for Hg(2+) in the literature. We also discovered DNA aptamers that bind to Cu(2+) with excellent affinity and specificity. Both aptamers were obtained within four rounds of screening, demonstrating the efficiency of our aptamer discovery method. Given the growing availability of FACS, we believe our method offers a general strategy for discovering high-quality aptamers for other ions and small-molecule targets in an efficient and reproducible manner. PMID- 27399154 TI - Combined Photoemission Spectroscopy and Electrochemical Study of a Mixture of (Oxy)carbides as Potential Innovative Supports and Electrocatalysts. AB - Active and stable non-noble metal materials, able to substitute Pt as catalyst or to reduce the Pt amount, are vitally important for the extended commercialization of energy conversion technologies, such as fuel cells and electrolyzers. Here, we report a fundamental study of nonstoichiometric tungsten carbide (WxC) and its interaction with titanium oxycarbide (TiOxCy) under electrochemical working conditions. In particular, the electrochemical activity and stability of the WxC/TiOxCy system toward the ethanol electrooxidation reaction (EOR) and hydrogen evolution reaction (HER) are investigated. The chemical changes caused by the applied potential are established by combining photoemission spectroscopy and electrochemistry. WxC is not active toward the ethanol electrooxidation reaction at room temperature but it is highly stable under these conditions thanks to the formation of a passive thin film on the surface, consisting mainly of WO2 and W2O5, which prevents the full oxidation of WxC. In addition, WxC is able to adsorb ethanol, forming ethoxy groups on the surface, which constitutes the first step for the ethanol oxidation. The interaction between WxC and TiOxCy plays an important role in the electrochemical stability of WxC since specific orientations of the substrate are able to stabilize WxC and prevent its corrosion. The beneficial interaction with the substrate and the specific surface chemistry makes tungsten carbide a good electrocatalyst support or cocatalyst for direct ethanol fuel cells. However, WxC is active toward the HER and chemically stable under hydrogen reduction conditions, since no changes in the chemical composition or dissolution of the film are observed. This makes tungsten carbide a good candidate as electrocatalyst support or cocatalyst for the electrochemical production of hydrogen. PMID- 27399155 TI - Voluntary motor commands reveal awareness and control of involuntary movement. AB - The capacity to inhibit actions is central to voluntary motor control. However, the control mechanisms and subjective experience involved in voluntarily stopping an involuntary movement remain poorly understood. Here we examined, in humans, the voluntary inhibition of the Kohnstamm phenomenon, in which sustained voluntary contraction of shoulder abductors is followed by involuntary arm raising. Participants were instructed to stop the involuntary movement, hold the arm in a constant position, and 'release' the inhibition after ~2s. Participants achieved this by modulating agonist muscle activity, rather than by antagonist contraction. Specifically, agonist muscle activity plateaued during this voluntary inhibition, and resumed its previous increase thereafter. There was no discernible antagonist activation. Thus, some central signal appeared to temporarily counter the involuntary motor drive, without directly affecting the Kohnstamm generator itself. We hypothesise a form of "negative motor command" to account for this novel finding. We next tested the specificity of the negative motor command, by inducing bilateral Kohnstamm movements, and instructing voluntary inhibition for one arm only. The results suggested negative motor commands responsible for inhibition are initially broad, affecting both arms, and then become focused. Finally, a psychophysical investigation found that the perceived force of the aftercontraction was significantly overestimated, relative to voluntary contractions with similar EMG levels. This finding is consistent with the hypothesis that the Kohnstamm generator does not provide an efference copy signal. Our results shed new light on this interesting class of involuntary movement, and provide new information about voluntary inhibition of action. PMID- 27399156 TI - Developmental and acute toxicity of cetylpyridinium chloride in Bombina orientalis (Amphibia: Anura). AB - In an effort to evaluate the toxicity of cetylpyridinium chloride (CPC), a cationic surfactant in amphibians, we examined the developmental and acute toxicity of CPC in Bombina orientalis embryos and tadpoles. Embryonic exposure to 2.0MUM (0.72mg/l) CPC for 7 days significantly decreased the survival rates and increased DNA damage in the intestine of developed tadpoles. Exposure to 1.5MUM (0.54mg/l) CPC significantly decreased the growth of embryos and increased developmental abnormalities. The 168-h LC50 and EC50 values of CPC were 1.95MUM (0.697mg/l) and 1.48MUM (0.531mg/l) in embryos, respectively. In an extended acute toxicity test using tadpoles, the 168-h LC50 value of CPC was 5.07MUM (1.82mg/l). In terms of survival and growth rates, the lowest observed effective concentration of CPC was 1.5MUM. At sub-lethal concentrations (1.0 and 2.0MUM) CPC treatment to embryos increased lipid peroxidation in the intestine and gills of developed tadpoles, indicating that CPC can impose oxidative stress. At 2.0MUM CPC, pro-apoptotic Bax and Bak mRNA levels were significantly increased together with DNA fragmentation, indicative of apoptotic cell death. CPC in freshwater system may threaten the normal development of amphibian embryos. PMID- 27399157 TI - Transcriptomic alterations in Daphnia magna embryos from mothers exposed to hypoxia. AB - Hypoxia occurs when dissolved oxygen (DO) falls below 2.8mgL(-1) in aquatic environments. It can cause trans-generational effects not only in fish, but also in the water fleas Daphnia. In this study, transcriptome sequencing analysis was employed to identify transcriptomic alterations induced by hypoxia in embryos of Daphnia magna, with an aim to investigate the mechanism underlying the trans generational effects caused by hypoxia in Daphnia. The embryos (F1) were collected from adults (F0) that were previously exposed to hypoxia (or normoxia) for their whole life. De novo transcriptome assembly identified 18270 transcripts that were matched to the UniProtKB/Swiss-Prot database and resulted in 7419 genes. Comparative transcriptome analysis showed 124 differentially expressed genes, including 70 up- and 54 down-regulated genes under hypoxia. Gene ontology analysis further highlighted three clusters of genes which revealed acclimatory changes of haemoglobin, suppression in vitellogenin gene family and histone modifications. Specifically, the expressions of histone H2B, H3, H4 and histone deacetylase 4 (HDAC4) were deregulated. This study suggested that trans generational effects of hypoxia on Daphnia may be mediated through epigenetic regulations of histone modifications. PMID- 27399158 TI - Procedure-Related Fetal Loss following Chorionic Villus Sampling after First Trimester Aneuploidy Screening. AB - OBJECTIVE: The aim was to determine the institutional procedure-related fetal loss rate after chorionic villus sampling (CVS) and the factors which may identify pregnancies at increased risk of having a procedure-related loss. MATERIALS AND METHODS: Pregnancy outcomes were retrieved of all women having a singleton pregnancy and undergoing a CVS procedure between 2004 and 2013 at a university hospital in Hong Kong. The incidence of procedure-related fetal loss due to unintended miscarriages adjusted for the background loss incidence of miscarriages was determined. Multivariate regression was performed to examine the factors contributing to an unintended fetal loss and miscarriage. RESULTS: CVS was performed on 1,906 fetuses. The procedure-related fetal loss rate was 0.17% (95% CI -0.2 to 0.7). After multivariate analysis, a decreased plasma protein-A (PAPP-A) multiple of the median (OR 0.27; 95% CI 0.08-0.98, p = 0.046) was significantly associated with miscarriage in women who did not undergo a CVS. Patient-specific prediction of spontaneous abortion in women who did not undergo CVS was not statistically significant (AUC 0.56; 95% CI 0.49-0.6, p = 0.14). CONCLUSIONS: The CVS-related fetal loss rate adjusted for background loss was 0.17%. Pregnancies with reduced PAPP-A carry an increased risk of miscarriage irrespective of whether they had undergone an invasive procedure. PMID- 27399160 TI - Synthesis, Crystal Structure, Theoretical, and Resistivity Study of BaUSe3. AB - The black-colored compound BaUSe3 has been synthesized at 1173 K by a stoichiometric reaction of the elements in a CsCl flux. BaUSe3 crystallizes in the GdFeO3 structure type. There is no change in structure between 100 and 298 K. The U atoms in this structure are octahedrally connected to six Se atoms. Each octahedral unit shares all six corners with neighboring octahedra, forming a three-dimensional network. BaUSe3 can be charge balanced as Ba(2+)U(4+)(Se(2-))3. DFT electronic structure calculations found BaUSe3 to be antiferromagnetic in its ground state and to be a semiconductor with a band gap of 2.5 eV. The band gap is inconsistent with the black color of the material and with the small activation energy of 0.12(1) eV obtained from resistivity measurements. A UV-vis spectrum indicated that there was no band gap above 1 eV. It is possible that, for BaUSe3, intrinsic and extrinsic impurities from the flux create midgap states that lead to the experimentally measured narrow optical gap. More likely, BaUSe3 presents a challenge to DFT calculations as applied to 5f materials. PMID- 27399159 TI - Hippocampus at 25. AB - The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. (c) 2016 Wiley Periodicals, Inc. PMID- 27399161 TI - Chronic kidney disease of unknown etiology in Sri Lanka. AB - INTRODUCTION: In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. METHODS: A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. RESULTS: Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. DISCUSSION: Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization. PMID- 27399162 TI - Intra-family stressors among adult siblings sharing caregiving for parents. AB - AIM: The aim of this study was to describe a Neuman Systems Model-guided study of perceptions of family stressors experienced by adult siblings who share caregiving for their parents and the influence of these stressors on adult siblings' relationships. BACKGROUND: The task of providing informal care for disabled parents is often shared by adult siblings. Family stressors experienced as part of caregiving may affect the sibling relationship. DESIGN: A mixed-method study design was used. METHODS: Data were collected during 2013-2014 from 84 adult sibling caregivers. Seventy-two caregivers provided quantitative data for the Lifespan Sibling Relationship Scale and the Zarit Burden Scale and 79 provided qualitative data for the open-ended question. RESULTS: Adult siblings experienced mild-to-moderate levels of burden from family stressors when they share parental caregiving. The amount of burden from intra-family stressors was negatively related to the adult sibling relationship. Beneficial and noxious stressors were evident in the participants' responses to an open-ended question. CONCLUSION: The health of the parents affected the lives of adult siblings in both negative and positive ways. Although the majority of the adult siblings expressed a willingness to care for their parent(s) in an attempt to reciprocate the care, they had received from them, challenges emerged from dealing with family stressors. PMID- 27399163 TI - Removal of stigmasterol from Kraft mill effluent by aerobic biological treatment with steroidal metabolite detection. AB - Stigmasterol is a phytosterol contained in Kraft mill effluent that is able to increase over 100% after aerobic biological treatment. This compound can act as an endocrine disrupter as its structure is similar to that of cholesterol. The aim of this study was to evaluate the removal of stigmasterol from Kraft mill effluents treated by a moving bed biofilm reactor (MBBR) with steroidal metabolite detection. The MBBR was operated for 145 days, with a hydraulic retention time of 2 days. Stigmasterol and steroidal metabolites were detected by gas chromatography with a flame ionization detector during MBBR operation. The results show that the MBBR removed 87.4% of biological oxygen demand (BOD5), 61.5% of chemical oxygen demand (COD), 24.5% of phenol and 31.5% of lignin, expressed in average values. The MBBR system successfully removed 100% of the stigmasterol contained in the influent (33 ug L(-1)) after 5 weeks of operation. In that case, the organic load rate was 0.343 kg COD m(-3) d(-1). Furthermore, different steroidal compounds (e.g., testosterone propionate, stigmast-4-en-3 one, 5alpha-pregnan-12-one-20alpha-hydroxy, 5alpha-pregnane-3,11,20-trione and 3alpha-hydroxy-5alpha-androstane-11,17-dione were detected in the Kraft mill effluent as potential products of phytosterol biotransformation. PMID- 27399164 TI - Endogenous plasma and salivary uracil to dihydrouracil ratios and DPYD genotyping as predictors of severe fluoropyrimidine toxicity in patients with gastrointestinal malignancies. AB - OBJECTIVE: The aim of this study was to evaluate the use of plasma and saliva uracil (U) to dihydrouracil (UH2) metabolic ratio and DPYD genotyping, as a means to identify patients with dihydropyrimidine dehydrogenase (DPD) deficiency and fluoropyrimidine toxicity. METHODS: Paired plasma and saliva samples were obtained from 60 patients with gastrointestinal cancer, before fluoropyrimidine treatment. U and UH2 concentrations were measured by LC-MS/MS. DPYD was genotyped for alleles *7, *2A, *13 and Y186C. Data on toxicity included grade 1 to 4 neutropenia, mucositis, diarrhea, nausea/vomiting and cutaneous rash. RESULTS: 35% of the patients had severe toxicity. There was no variant allele carrier for DPYD. The [UH2]/[U] metabolic ratios were 0.09-26.73 in plasma and 0.08-24.0 in saliva, with higher correlation with toxicity grade in saliva compared to plasma (rs=-0.515 vs rs=-0.282). Median metabolic ratios were lower in patients with severe toxicity as compared to those with absence of toxicity (0.59 vs 2.83 saliva; 1.62 vs 6.75 plasma, P<0.01). A cut-off of 1.16 for salivary ratio was set (AUC 0.842), with 86% sensitivity and 77% specificity for the identification of patients with severe toxicity. Similarly, a plasma cut-off of 4.0 (AUC 0.746), revealed a 71% sensitivity and 76% specificity. CONCLUSIONS: DPYD genotyping for alleles 7, *2A, *13 and Y186C was not helpful in the identification of patients with severe DPD deficiency in this series of patients. The [UH2]/[U] metabolic ratios, however, proved to be a promising functional test to identify the majority of cases of severe DPD activity, with saliva performing better than plasma. PMID- 27399165 TI - Q Sepharose micro-column chromatography: A simple screening method for identifying beta thalassemia traits and hemoglobin E carriers. AB - OBJECTIVES: For beta thalassemia control program in pregnancy, mass screening of the carrier state by determination of the hemoglobin (Hb) A2 and Hb E proportions and mutation analysis is a preferred method for making prenatal diagnoses. Q Sepharose micro-column chromatography, developed for the determination of Hb A2 and Hb E for screening purposes, was compared with high performance liquid chromatography (HPLC) to ascertain its relative accuracy and reliability. DESIGN AND METHODS: Results using Q Sepharose micro-column chromatography in 350 blood specimens, including 50 samples genetically proven to be beta thalassemia heterozygotes, were compared to HPLC for validation. An additional study was conducted to test a clinical application on a large-scale survey for beta thalassemia in 1581 pregnant women and their spouses. RESULTS: The mean (+/-SD) Hb A2 proportions in the normal and genetically proven beta thalassemia heterozygotes were 2.70+/-0.40% and 6.30+/-1.23%, respectively, as determined by Q-Sepharose micro-column chromatography, and 2.65+/-0.31% and 5.37+/-0.96%, respectively, as determined by HPLC. The mean Hb E proportions in the Hb E heterozygotes were 23.25+/-4.13% and 24.72+/-3.5% as determined by Q Sepharose micro-column chromatography and HPLC, respectively. In the large-scale survey for beta thalassemia, 23 at risk couples were detected. Seven affected fetuses were identified by prenatal diagnosis. CONCLUSIONS: Q Sepharose micro-column chromatography was found to be reliable, reproducible and well-suited for large scale surveys. Additionally, by being reusable and convenient, this simple and economical chromatography method may be an alternative means to screen for beta thalassemia and Hb E carriers in the mass population. PMID- 27399166 TI - Influence of ADORA2A gene polymorphism on leukoencephalopathy risk in MTX-treated pediatric patients affected by hematological malignancies. AB - BACKGROUND: Methotrexate (MTX) can lead to neurotoxicity and asymptomatic leukoencephalopathy. However, the mechanism of MTX-related leukoencephalopathy is obscure. MTX and its metabolites inhibit 5-aminoimidazole-4-carboxamide ribonucleotide formiltransferase (ATIC) and promote adenosine release. Recently, it has been reported that adenosine and its receptor are related to certain central nervous system diseases. We investigated whether adenosine pathway gene polymorphisms and clinical factors were related to MTX-related leukoencephalopathy in pediatric patients affected by hematological malignancies. PROCEDURE: Fifty-six Japanese childhood acute lymphoblastic leukemia or lymphoma patients were investigated. Patients were evaluated by magnetic resonance imaging of the brain before maintenance therapy or stem cell transplantation. Gene polymorphisms within the adenosine pathway (ATIC, adenosine A2A receptor [ADORA2A]) and the MTX pathway (methylenetetrahydrofolate reductase [MTHFR] and ABCB1) were genotyped using TaqMan assays. Clinical data were collected by accessing the medical records. MTX-related leukoencephalopathy was evaluated by a pediatric neurologist. RESULTS: Twenty-one (37%) of 56 patients developed MTX related leukoencephalopathy. Four of 21 patients developed clinical neurotoxicity. The minor allele CC genotype of rs2298383 (ADORA2A) was associated with MTX-related leukoencephalopathy (P = 0.010, odds ratio = 5.81, 95% confidence interval 1.50-22.50). High cumulative dose of systemic MTX was associated with MTX-related leukoencephalopathy after adjusting for sex, ADORA2A polymorphism, and prolonged high MTX concentration (P = 0.042, odds ratio = 1.18, 95% confidence interval 1.01-1.37). CONCLUSIONS: ADORA2A rs2298383 and high cumulative dose of systemic MTX administration were significantly associated with MTX-related leukoencephalopathy. Our results indicate that pharmacological intervention within the adenosine pathway may be both a treatment and preventative option for MTX-related leukoencephalopathy. PMID- 27399167 TI - The emerging trend of self-circumcision and the need to define cause: Case report of a 21 year-old male. AB - INTRODUCTION: Male circumcision is traditionally carried out by ascribed practitioners, so self-circumcision is very rare. It is intriguing why the victims should not seek available modern health care. This article highlights another case of self-circumcision, the related causes, complications and their management. The gradual increase in numbers is contributing to the surgical disease burden. CASE PRESENTATION: A 21year old male circumcised himself using a razor-blade 13days prior to presentation at the hospital. He attributes this to reluctance to have him circumcised. He sustained extensive penile skin denudation of 7cm in length, severe bleeding and pain. He lives close to traditionally circumcising communities and was once chided by peers for being uncircumcised. He had no evidence of psychosis. He did not use any medications during the procedure. He was managed with analgesics, antibiotics and surgical reconstruction. He was discharged on the second post-operative day and subsequently recovered fully. DISCUSSION: Such patients face a variety of complications, both the immediate and long term. Some are fatal especially those with systemic effects including haemorrhagic shock and septicaemia associated with gangrene. Timely referral to specialist surgeons is critical, as well as thorough review and control of the causes prompting this practice. CONCLUSION: Cases of self-circumcision continue to emerge. There is need to report all cases, explore and manage the possible causes. The stigma uncircumcised males face among circumcised peers may be an important cause. Public health education and improved access to voluntary medical male circumcision services may help to prevent this practice. PMID- 27399168 TI - An unusual presentation of congenital intestinal malrotation in a nonagenarian. AB - INTRODUCTION: Appendicitis is a common surgical pathology with many clinical presentations. Diagnosis can be challenging if there is an alteration to the normal position of anatomical structures and their relationships. CASE PRESENTATION: In this case, we report an unusual presentation of congenital intestinal malrotation in a nonagenarian presenting with generalized abdominal pain and lactic acidosis found to have perforated appendicitis. The patient was admitted to the Hospitalist service for abdominal pain and misdiagnosed with bowel obstruction secondary to previous "operation". After further review of imaging malrotation with internal hernia was suggested. The patient was taken emergently to the operating room and found to have perforated and gangrenous appendix in the midabdomen. An appendectomy was performed and patient was ultimately discharged home in good condition on postoperative day four. DISCUSSION: Malrotation of the intestines is a developmental variant that occurs when normal fetal rotation of the intestines around the superior mesenteric artery and their peritoneal fixation fails to occur. Presentation typically occurs during infancy and diagnosis in an elderly patient is exceedingly rare. Operative intervention is often required as it is commonly associated with lactic acidosis or peritonitis. CONCLUSIONS: Malrotation can go undiagnosed well into elderly life and can present with unusual signs and symptoms. CT is very helpful in aiding the diagnosis but itself can be misleading. PMID- 27399169 TI - Dysfunction of small airways and prevalence, airway responsiveness and inflammation in asthma: much more than small particle size of pet animal allergens. PMID- 27399170 TI - Exploring structural features of folded peptide architectures in the construction of nanomaterials. AB - We are reporting the influence of foldamer structures on their self-assembled architectures. In a sharp contrast to the ordered alpha,gamma-hybrid 12-helix obtained from 1 : 1 alternating Aib and gamma-Phe, the alpha,gamma-hybrid peptides constituted with alpha-Phe and 4,4-dimethyl gamma-amino acid (Aic) displayed the extended sheet type of conformations in solution and spontaneously self-assembled into thermally and proteolytically stable capsules. In contrast, the conformationally ordered 12-helix self-assembled into a three-dimensional supramolecular polyhedron. PMID- 27399171 TI - Copper comes of age in Melbourne. AB - When we were asked to produce articles for this volume, it seemed appropriate to us to co-author an article on the history and impact of copper research in Melbourne. It is appropriate because over many years, decades in fact, we worked closely together and with Professor David Danks to identify the molecular defect in Menkes disease. This work was always carried out with the intention of understanding the nature of the copper homeostatic mechanisms and a "copper pathway" in the cell, that David had the prescience to predict must exist despite scepticism from granting agencies! He indeed inspired us to pursue research careers in this field. This article outlines some of this history. PMID- 27399172 TI - Double Trouble: Kinase domain duplication as a new path to drug resistance. PMID- 27399173 TI - Computer-Assisted Evaluation of Retinal Vessel Diameter in Retinitis Pigmentosa. AB - PURPOSE: The evaluation of retinal vessel attenuation is very subjective and not sufficiently reliable in patients with retinitis pigmentosa (RP). We tested semiautomatic software capable of obtaining real-time measurements of vessel diameter. METHODS: Retinal vessel diameter was calculated in 25 RP subjects and in 20 healthy controls. The Mann-Whitney test was used to compare the average values of RP patients with those of controls and subgroups of RP patients with different clinical features. RESULTS: The retinal vessel diameter was significantly smaller in RP patients than in controls (p < 0.001). In particular, vessel diameters were smaller in older subjects, in patients with worse ERG responses, and in patients with more severe visual field loss. CONCLUSIONS: Computer-assisted analysis of retinal fundus pictures may be helpful in the diagnosis of RP and in monitoring disease progression. PMID- 27399174 TI - Bidirectional Relations Between Temperament and Parenting Predicting Preschool Age Children's Adjustment. AB - Bidirectional associations between child temperament (fear, frustration, positive affect, effortful control) and parenting behaviors (warmth, negativity, limit setting, scaffolding, responsiveness) were examined as predictors of preschool age children's adjustment problems and social competence. Participants were a community sample of children (N = 306; 50% female, 64% European American) and their mothers. Observational measures of child temperament and parenting were obtained using laboratory tasks at two time points (children's ages 36 and 54 months). Teacher-reported adjustment measures were collected at the first and third time points (children's ages 36 and 63 months). Cross-lagged analyses were performed to examine whether child temperament and parenting predict changes in one another, whether they each contribute independently to children's adjustment, and whether these transactional relations account for adjustment outcomes. Maternal negativity at 36 months predicted increases in child frustration at 54 months. Maternal negativity and child effortful control predicted decreases in each other from 36 to 54 months. Maternal warmth predicted increases in child effortful control over time. Child frustration, child effortful control, maternal warmth, and maternal negativity at 54 months each independently predicted child adjustment problems at 63 months, controlling for problems at 36 months. Child executive control at 54 months predicted increases in child social competence at 63 months. The findings suggest that temperament and parenting have independent and additive effects on preschool-age child adjustment, with some support for a bidirectional relation. PMID- 27399175 TI - Diet-induced obesity regulates adipose-resident stromal cell quantity and extracellular matrix gene expression. AB - Adipose tissue expansion during periods of excess nutrient intake requires significant turnover of the extracellular matrix (ECM) to allow for maximal lipid filling. Recent data suggest that stromal cells may be a primary contributor to ECM modifications in visceral adipose. The purpose of this study was to investigate the capacity for high fat diet (HFD)-induced obesity to alter adipose derived stromal cell (ADSC) relative quantity and ECM gene expression, and determine the extent to which exercise training can mitigate such changes. Male C57BL/6J mice were placed on control or HFD for 8weeks prior to and following initiation of a 16week treadmill exercise program. ADSCs (Sca-1(+)CD45(-)) were isolated from epididymal adipose tissue and mRNA was evaluated using high throughput qPCR. Stromal cells were also obtained from skeletal muscle (MDSC). HFD decreased the quantity of ADSCs and markedly altered gene expression related to ECM remodeling (Col1alpha1, MMP2, MMP9, Timp1). Exercise did not reverse these changes. MDSCs were minimally altered by HFD or exercise. Overall, the data from this study suggest that ADSCs decrease in quantity and contribute to adipose ECM remodeling in response to obesity, and exercise training does not significantly impact these outcomes. PMID- 27399177 TI - eReaxFF: A Pseudoclassical Treatment of Explicit Electrons within Reactive Force Field Simulations. AB - We present a computational tool, eReaxFF, for simulating explicit electrons within the framework of the standard ReaxFF reactive force field method. We treat electrons explicitly in a pseudoclassical manner that enables simulation several orders of magnitude faster than quantum chemistry (QC) methods, while retaining the ReaxFF transferability. We delineate here the fundamental concepts of the eReaxFF method and the integration of the Atom-condensed Kohn-Sham DFT approximated to second order (ACKS2) charge calculation scheme into the eReaxFF. We trained our force field to capture electron affinities (EA) of various species. As a proof-of-principle, we performed a set of molecular dynamics (MD) simulations with an explicit electron model for representative hydrocarbon radicals. We establish a good qualitative agreement of EAs of various species with experimental data, and MD simulations with eReaxFF agree well with the corresponding Ehrenfest dynamics simulations. The standard ReaxFF parameters available in the literature are transferrable to the eReaxFF method. The computationally economic eReaxFF method will be a useful tool for studying large scale chemical and physical systems with explicit electrons as an alternative to computationally demanding QC methods. PMID- 27399178 TI - Letters. PMID- 27399179 TI - Sportspages. PMID- 27399176 TI - Personalized and targeted therapy of esophageal squamous cell carcinoma: an update. AB - Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research. In this review, we update recent progress in the research area of targeted therapy for ESCC. SOX2 and its associated proteins (e.g., DeltaNP63alpha), which regulate lineage survival of ESCC cells, are proposed as therapeutic targets. It is believed that targeting the lineage-survival mechanism may be more effective than targeting other mechanisms. With the advent of a new era of personalized targeted therapy, there is a need to move from the tumor centric model into an organismic model. PMID- 27399181 TI - 'Athlete, Heal Thyself,' Says Physician. PMID- 27399180 TI - A need to know. PMID- 27399182 TI - Six Beers, Six Miles; Six Beers, No Miles. PMID- 27399183 TI - Big Report Has Little on Sportsmedicine. PMID- 27399184 TI - Mountaineering Medicine. PMID- 27399186 TI - Cme credit quiz. PMID- 27399185 TI - Medical Aspects of Mountain Climbing. PMID- 27399187 TI - The Iditarod: Alaskan Challenge. PMID- 27399188 TI - Easing Athletes' Anxiety at the Winter Olympics. PMID- 27399189 TI - Blind Break Through Old Barriers to Sports. PMID- 27399190 TI - Nationwide Sports Aptitude Screening. PMID- 27399191 TI - Scanning sports. PMID- 27399192 TI - Stretching Exercises for Flexibility. PMID- 27399194 TI - World at play. AB - In the fields of sports and sportsmedicine today a prime topic of conversation is the approach to training and competition taken by the Communist nations, notably the Soviet Union and East Germany. Their achievements in the Olympics and elsewhere, plus reports of their intense medical analysis and monitoring of athletes, have built something of a mystical aura about these nations. What are they doing in sports? The Physician and Sportsmedicine has obtained accounts of activity in both countries. Alois Marder, MD, currently an assistant professor at the Sports School for Elite Athletes in Cologne, West Germany, served from 1964 to 1974 as a physician attached to the Leipzig Sports Institute for Elite Athletes in East Germany. Editor-in-Chief Allan J. Ryan, MD, recently spoke at length with him about sports and sportsmedicine in East Germany. Jess Jarver, sports development officer for the Department of Tourism, Recreation and Sport for South Australia, toured the Soviet Union. Their reports follow. PMID- 27399196 TI - Outcome After Pneumonectomy in 17 Dogs and 10 Cats: A Veterinary Society of Surgical Oncology Case Series. AB - OBJECTIVE: To report the signalment, presenting clinical signs, surgical complications, histologic diagnosis, postoperative complications, and outcome of dogs and cats undergoing pneumonectomy. STUDY DESIGN: Retrospective case series; multicenter study. ANIMALS: Client-owned dogs (n=17) and cats (n=10). METHODS: Signalment, clinical signs, side affected, surgical data, preoperative diagnostic tests (including complete blood count, serum biochemistry, cytologic diagnosis, chest radiographs, and computed tomography), histologic diagnosis, surgical complications, adjunctive therapy, and date and cause of death were collected from records of dogs and cats that underwent pneumonectomy. Survival estimates and complication were assessed. RESULTS: Seventeen animals had a left-sided pneumonectomy performed (12 dogs, 5 cats) and 10 animals had a right-sided pneumonectomy (5 dogs, 5 cats). Fourteen animals were diagnosed with neoplasia (52%). The overall incidence of complications for dogs and cats were 76 and 80%, respectively, with major complications in 41 and 50%, respectively. Respiratory complications (persistent pleural effusion, oxygen dependence, persistent increased respiratory rate, or coughing) were the most frequent complications. No animals died or were euthanatized intraoperative or within the first 24 hours postoperative. One dog (6%) and 2 cats (20%) died, or were euthanatized in the first 2 weeks postoperative. CONCLUSION: Based on this case series, right and left pneumonectomy can be performed with low perioperative mortality in dogs and cats, with some animals experiencing prolonged survival. PMID- 27399197 TI - Subgroup analysis of Asian patients in the INPULSIS(r) trials of nintedanib in idiopathic pulmonary fibrosis. AB - BACKGROUND AND OBJECTIVE: In the two-replicate randomized Phase III INPULSIS(r) trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. METHODS: Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS(r) trials. Safety data were analyzed descriptively. RESULTS: Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). CONCLUSION: In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS(r) trials, race did not influence the effect of nintedanib on disease progression. PMID- 27399198 TI - Special Shoes for the Management of Knee Osteoarthritis Symptoms. PMID- 27399199 TI - Dynamics of the Fouling Layer Microbial Community in a Membrane Bioreactor. AB - Membrane fouling presents the greatest challenge to the application of membrane bioreactor (MBR) technology. Formation of biofilms on the membrane surface is the suggested cause, yet little is known of the composition or dynamics of the microbial community responsible. To gain an insight into this important question, we applied 16S rRNA gene amplicon sequencing with a curated taxonomy and fluorescent in situ hybridization to monitor the community of a pilot-scale MBR carrying out enhanced biological nitrogen and phosphorus removal with municipal wastewater. In order to track the dynamics of the fouling process, we concurrently investigated the communities of the biofilm, MBR bulk sludge, and the conventional activated sludge system used to seed the MBR system over several weeks from start-up. As the biofilm matured the initially abundant betaproteobacterial genera Limnohabitans, Hydrogenophaga and Malikia were succeeded by filamentous Chloroflexi and Gordonia as the abundant species. This study indicates that, although putative pioneer species appear, the biofilm became increasingly similar to the bulk community with time. This suggests that the microbial population in bulk water will largely determine the community structure of the mature biofilm. PMID- 27399200 TI - Likelihood ratio tests for a dose-response effect using multiple nonlinear regression models. AB - We consider the problem of testing for a dose-related effect based on a candidate set of (typically nonlinear) dose-response models using likelihood-ratio tests. For the considered models this reduces to assessing whether the slope parameter in these nonlinear regression models is zero or not. A technical problem is that the null distribution (when the slope is zero) depends on non-identifiable parameters, so that standard asymptotic results on the distribution of the likelihood-ratio test no longer apply. Asymptotic solutions for this problem have been extensively discussed in the literature. The resulting approximations however are not of simple form and require simulation to calculate the asymptotic distribution. In addition, their appropriateness might be doubtful for the case of a small sample size. Direct simulation to approximate the null distribution is numerically unstable due to the non identifiability of some parameters. In this article, we derive a numerical algorithm to approximate the exact distribution of the likelihood-ratio test under multiple models for normally distributed data. The algorithm uses methods from differential geometry and can be used to evaluate the distribution under the null hypothesis, but also allows for power and sample size calculations. We compare the proposed testing approach to the MCP-Mod methodology and alternative methods for testing for a dose-related trend in a dose-finding example data set and simulations. PMID- 27399202 TI - Analysis of the Trypanosoma brucei EATRO 164 Bloodstream Guide RNA Transcriptome. AB - The mitochondrial genome of Trypanosoma brucei contains many cryptogenes that must be extensively edited following transcription. The RNA editing process is directed by guide RNAs (gRNAs) that encode the information for the specific insertion and deletion of uridylates required to generate translatable mRNAs. We have deep sequenced the gRNA transcriptome from the bloodstream form of the EATRO 164 cell line. Using conventionally accepted fully edited mRNA sequences, ~1 million gRNAs were identified. In contrast, over 3 million reads were identified in our insect stage gRNA transcriptome. A comparison of the two life cycle transcriptomes show an overall ratio of procyclic to bloodstream gRNA reads of 3.5:1. This ratio varies significantly by gene and by gRNA populations within genes. The variation in the abundance of the initiating gRNAs for each gene, however, displays a trend that correlates with the developmental pattern of edited gene expression. A comparison of related major classes from each transcriptome revealed a median value of ten single nucleotide variations per gRNA. Nucleotide variations were much less likely to occur in the consecutive Watson-Crick anchor region, indicating a very strong bias against G:U base pairs in this region. This work indicates that gRNAs are expressed during both life cycle stages, and that differential editing patterns observed for the different mitochondrial mRNA transcripts are not due to the presence or absence of gRNAs. However, the abundance of certain gRNAs may be important in the developmental regulation of RNA editing. PMID- 27399203 TI - Prevalence and Outcome of Mitochondrial Epilepsy. PMID- 27399204 TI - HLA Mismatch and Allograft Survival. PMID- 27399201 TI - Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture. AB - Foamy viruses (FV) belong to the genus Spumavirus, which forms a distinct lineage in the Retroviridae family. Although the infection in natural hosts and zoonotic transmission to humans is asymptomatic, FVs can replicate well in human cells making it an attractive gene therapy vector candidate. Here we present cryo electron microscopy and (cryo-)electron tomography ultrastructural data on purified prototype FV (PFV) and PFV infected cells. Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N terminal domain and the cytoplasmic part of the Env leader peptide gp18LP. The viral membrane contains trimeric Env glycoproteins partly arranged in interlocked hexagonal assemblies. In situ 3D reconstruction by subtomogram averaging of wild type Env and of a Env gp48TM- gp80SU cleavage site mutant showed a similar spike architecture as well as stabilization of the hexagonal lattice by clear connections between lower densities of neighboring trimers. Cryo-EM was employed to obtain a 9 A resolution map of the glycoprotein in its pre-fusion state, which revealed extensive trimer interactions by the receptor binding subunit gp80SU at the top of the spike and three central helices derived from the fusion protein subunit gp48TM. The lower part of Env, presumably composed of interlaced parts of gp48TM, gp80SU and gp18LP anchors the spike at the membrane. We propose that the gp48TM density continues into three central transmembrane helices, which interact with three outer transmembrane helices derived from gp18LP. Our ultrastructural data and 9 A resolution glycoprotein structure provide important new insights into the molecular architecture of PFV and its distinct evolutionary relationship with other members of the Retroviridae. PMID- 27399205 TI - Effects of severity of gross motor disability on anticipatory postural adjustments while standing in individuals with bilateral spastic cerebral palsy. AB - BACKGROUND: Although individuals with bilateral spastic cerebral palsy (BSCP) exhibit several deficits in anticipatory postural adjustments (APAs) while standing, effects of severity of motor disability on their APAs are unclear. AIMS: To determine whether individuals with BSCP exhibit severity-dependent deficits in APAs. METHODS AND PROCEDURES: Seven individuals with level II BSCP (BSCP-II group) and seven with level III BSCP (BSCP-III group) according to the Gross Motor Function Classification System and seven healthy controls lifted a load under two different load conditions. OUTCOMES AND RESULTS: Anticipatory activities of the erector spinae (ES), medial hamstring (MH), and gastrocnemius (GCM) were smaller in the two BSCP groups than in the control group. Although the anticipatory GCM activity was similar between the BSCP groups, the ES and MH activities were larger in the BSCP-II group than in the BSCP-III group. In the BSCP-II group, an increase in anticipatory activity with an increase in load was observed in the MH, but not in the GCM. In the BSCP-III group, load-related modulation was not found in the MH or GCM. CONCLUSIONS AND IMPLICATIONS: The present findings suggest that in individuals with BSCP with severe motor disability, APA deficits extend to more proximal parts of the body. PMID- 27399206 TI - Motor imagery difficulties in children with Cerebral Palsy: A specific or general deficit? AB - AIM: The aim of this study was to examine the specificity of motor imagery (MI) difficulties in children with CP. METHOD: Performance of 22 children with CP was compared to a gender and age matched control group. MI ability was measured with the Hand Laterality Judgment (HLJ) task, examining specifically the direction of rotation (DOR) effect, and the Praxis Imagery Questionnaire (PIQ). RESULTS: In the back view condition of the HLJ task both groups used MI, as evidenced by longer response times for lateral compared with medial rotational angles. In the palm view condition children with CP did not show an effect of DOR, unlike controls. Error scores did not differ between groups. Both groups performed well on the PIQ, with no significant difference between them in response pattern. CONCLUSION AND IMPLICATION: The present study suggests that children with CP show deficits on tasks that trigger implicit use of MI, whereas explicit MI ability was relatively preserved, as assessed using the PIQ. These results suggest that employing more explicit methods of MI training may well be more suitable for children with CP in rehabilitation of motor function. PMID- 27399207 TI - Electromagnetic homeostasis and the role of low-amplitude electromagnetic fields on life organization. AB - The appearance of endogenous electromagnetic fields in biological systems is a widely debated issue in modern science. The electrophysiological fields have very tiny intensities and it can be inferred that they are rapidly decreasing with the distance from the generating structure, vanishing at very short distances. This makes very hard their detection using standard experimental methods. However, the existence of fast-moving charged particles in the macromolecules inside both intracellular and extracellular fluids may envisage the generation of localized electric currents as well as the presence of closed loops, which implies the existence of magnetic fields. Moreover, the whole set of oscillatory frequencies of various substances, enzymes, cell membranes, nucleic acids, bioelectrical phenomena generated by the electrical rhythm of coherent groups of cells, cell-to cell communication among population of host bacteria, forms the increasingly complex hierarchies of electromagnetic signals of different frequencies which cover the living being and represent a fundamental information network controlling the cell metabolism. From this approach emerges the concept of electromagnetic homeostasis: that is, the capability of the human body to maintain the balance of highly complex electromagnetic interactions within, in spite of the external electromagnetic noisy environment. This concept may have an important impact on the actual definitions of heal and disease. PMID- 27399208 TI - Protective Effects of Liquiritin on the Brain of Rats with Alzheimer's Disease. AB - Background: Alzheimer's disease (AD) is a sort of nerve degenerative disease with clinical manifestation of memory damage and cognitive dysfunction. Its typical pathological change is the abnormal deposition of amyloid-beta (Abeta). Method: In this study, a rat AD model with liquiritin (LQ) interference was established to observe the effects of LQ on the AD rats' behavioural memory and primary hippocampus cells. Results: Liquiritin had the effect of improving the rats' learning and memory ability, enhancing the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in rats' brain tissues, increasing the antioxidant ability, protecting the primary cultured hippocampal neurons and inhibiting the apoptosis induced by Abeta25-35. Conclusion: The protective effects of LQ can be related to the enhancement of antioxidase activity and clearance of oxygen radicals. PMID- 27399209 TI - An extracellular Zn-only superoxide dismutase from Puccinia striiformis confers enhanced resistance to host-derived oxidative stress. AB - Accumulation of reactive oxygen species (ROS) following plant-pathogen interactions can trigger plant defence responses and directly damage pathogens. Thus, it is essential for pathogens to scavenge host-derived ROS to establish a parasitic relationship. However, the mechanisms protecting pathogens from host derived oxidative stress remain unclear. In this study, a superoxide dismutase (SOD) gene, PsSOD1, was cloned from a wheat-Puccinia striiformis f. sp. tritici (Pst) interaction cDNA library. Transcripts of PsSOD1 were up-regulated in the early infection stage. Heterologous mutant complementation and biochemical characterization revealed that PsSOD1 encoded a Zn-only SOD. The predicted signal peptide was functional in an invertase-mutated yeast strain. Furthermore, immunoblot analysis of apoplastic proteins in Pst-infected wheat leaves and bimolecular fluorescence complementation suggested that PsSOD1 is a secreted protein that potentially forms a dimer during Pst infection. Overexpression of PsSOD1 enhanced Schizosaccharomyces pombe resistance to exogenous superoxide. Transient expression of PsSOD1 in Nicotiana benthamiana suppressed Bax-induced cell death. Knockdown of PsSOD1 using a host-induced gene silencing (HIGS) system reduced the virulence of Pst, which was associated with ROS accumulation in HIGS plants. These results suggest that PsSOD1 is an important pathogenicity factor that is secreted into the host-pathogen interface to contribute to Pst infection by scavenging host-derived ROS. PMID- 27399211 TI - The Diagnostic Concordance of Whole Slide Imaging and Light Microscopy: A Systematic Review. AB - CONTEXT: -Light microscopy (LM) is considered the reference standard for diagnosis in pathology. Whole slide imaging (WSI) generates digital images of cellular and tissue samples and offers multiple advantages compared with LM. Currently, WSI is not widely used for primary diagnosis. The lack of evidence regarding concordance between diagnoses rendered by WSI and LM is a significant barrier to both regulatory approval and uptake. OBJECTIVE: -To examine the published literature on the concordance of pathologic diagnoses rendered by WSI compared with those rendered by LM. DATA SOURCES: -We conducted a systematic review of studies assessing the concordance of pathologic diagnoses rendered by WSI and LM. Studies were identified following a systematic search of Medline (Medline Industries, Mundelein, Illinois), Medline in progress (Medline Industries), EMBASE (Elsevier, Amsterdam, the Netherlands), and the Cochrane Library (Wiley, London, England), between 1999 and March 2015. CONCLUSIONS: Thirty-eight studies were included in the review. The mean diagnostic concordance of WSI and LM, weighted by the number of cases per study, was 92.4%. The weighted mean kappa coefficient between WSI and LM was 0.75, signifying substantial agreement. Of the 30 studies quoting percentage concordance, 18 (60%) showed a concordance of 90% or greater, of which 10 (33%) showed a concordance of 95% or greater. This review found evidence to support a high level of diagnostic concordance. However, there were few studies, many were small, and they varied in quality, suggesting that further validation studies are still needed. PMID- 27399212 TI - Naissance of the Archives of Pathology & Laboratory Medicine: A Critical Analysis of the January 1926, Volume 1 Issue. PMID- 27399213 TI - PD-1/PD-L1, Only a Piece of the Puzzle. PMID- 27399215 TI - Insomnia in the Hospital-Not Just a Bad Dream. PMID- 27399219 TI - The Option of Replacing the Special Supplemental Nutrition Program for Women, Infants, and Children Fruit Juice Supplements With Fresh Fruits and Vegetables. PMID- 27399214 TI - New insights into the regulation by RUNX1 and GFI1(s) proteins of the endothelial to hematopoietic transition generating primordial hematopoietic cells. AB - The first hematopoietic cells are generated very early in ontogeny to support the growth of the embryo and to provide the foundation to the adult hematopoietic system. There is a considerable therapeutic interest in understanding how these first blood cells are generated in order to try to reproduce this process in vitro. This would allow generating blood products, or hematopoietic cell populations from embryonic stem (ES) cells, induced pluripotent stem cells or through directed reprogramming. Recent studies have clearly established that the first hematopoietic cells originate from a hemogenic endothelium (HE) through an endothelial to hematopoietic transition (EHT). The molecular mechanisms underlining this transition remain largely unknown with the exception that the transcription factor RUNX1 is critical for this process. In this Extra Views report, we discuss our recent studies demonstrating that the transcriptional repressors GFI1 and GFI1B have a critical role in the EHT. We established that these RUNX1 transcriptional targets are actively implicated in the downregulation of the endothelial program and the loss of endothelial identity during the formation of the first blood cells. In addition, our results suggest that GFI1 expression provides an ideal novel marker to identify, isolate and study the HE cell population. PMID- 27399220 TI - Predictors of Paracentesis in Women with Severe Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study. AB - BACKGROUND: To identify predictors of paracentesis in women with severe ovarian hyperstimulation syndrome (OHSS). METHODS: In a retrospective cohort study, we assessed patient characteristics and outcome measures of women with severe OHSS Golan grade II/III from 1996 to 2010 using univariate and multivariate analyses with the number of paracenteses as the main outcome. RESULTS: Three hundred ninety four women with OHSS Golan grade II (n = 40) and grade III (n = 354) were included in the study. Paracentesis was performed in 108/394 (27%) of these women. One paracentesis was performed in 63 (16%), 2 paracenteses in 26 (6%), and >=3 paracenteses 19 (5%) women, respectively. No thrombotic or cerebrovascular morbidity occurred. The mortality of the cohort was 0/394 (0%). In a univariate analysis, late onset OHSS (p = 0.02), pregnancy (p < 0.001), human chorionic gonadotropin use (p = 0.02), ovarian diameter (p = 0.006), and elevated serum levels of alanine aminotransferase (p < 0.001), hematocrit (p < 0.001), leucocytes (p < 0.001), thrombocytes (p < 0.001), and uric acid (p < 0.001) were associated with paracentesis. In a multivariate logistic regression analysis, only alanine aminotransferase (OR 1.006; 95% CI 1.001-1.01) and hematocrit (OR 1.16; 95% CI 1.05-1.27) were independently associated with paracentesis. CONCLUSION: Alanine aminotransferase and hematocrit at initial presentation are independent predictors of paracentesis. PMID- 27399221 TI - The treatment of dual ADHD: a drop in the ocean. AB - Editorial of vol 28-3. PMID- 27399222 TI - Predictive Capacity of Cloninger's temperament and character inventory (TCI-R) in alcohol use disorder outcomes. AB - OBJECTIVE: to investigate the ability to predict the outcome of alcohol use disorders through Cloninger's temperament and character inventory (TCI-R). METHODS: this is a prospective study consisting of 237 outpatients with alcohol use disorders who underwent follow-up treatment for 6 months and whose personality traits were studied using TCI-R. At the end of that period, the scores of each TCI-R trait were analyzed in terms of those who remained in treatment and those who dropped out. RESULTS: The whole group scored highly in novelty seeking (NS) and harm avoidance (HA) and produced low scores in self directedness (SD), these last traits are considered prominent. The drop-out group scored significantly (p=.004) higher in novelty seeking (NS) than the follow-up group. Also, when the score was higher than the 67 percentile the likelihood of abandoning the treatment was 1.07 times higher. CONCLUSIONS: Cloninger's temperament and character inventory is a good instrument to predict the outcome of treatment of patients with alcohol use disorders and the novelty seeking (NS) dimension is strongly related to therapeutic drop-out. PMID- 27399223 TI - Psychotic-like Experiences and Substance Use in College Students. AB - Psychotic disorders, as well as psychotic-like experiences and substance use, have been found to be associated. The main goal of the present study was to analyse the relationship between psychoticlike experiences and substance use in college students. The simple comprised a total of 660 participants (M = 20.3 years, SD = 2.6). The results showed that 96% of the sample reported some delusional experience, while 20.3% reported at least one positive psychotic-like experience. Some substance use was reported by 41.1% of the sample, differing in terms of gender. Substance users reported more psychoticlike experiences than non users, especially in the positive dimension. Also, alcohol consumption predicted in most cases extreme scores on measures of delusional ideation and psychotic experiences. The association between these two variables showed a differentiated pattern, with a stronger relationship between substance use and cognitive perceptual psychotic-like experiences. To some extent, these findings support the dimensional models of the psychosis phenotype and contribute a better understanding of the links between psychoticlike experiences and substance use in young adults. Future studies should further explore the role of different risk factors for psychotic disorders and include models of the gene-environment interaction. PMID- 27399224 TI - Persistent psychotic symptoms after long-term heavy use of mephedrone: A two-case series. AB - Mephedrone (4-methylmethcathinone) is a synthetic stimulant drug of the cathinone class. Similar effects to those of cocaine and ecstasy are reported by users, with a high addictive potential. Given its increasing rate of consumption in Europe, it is getting more and more attention from the addiction field. In spite of that, little is known about the long-term consequences of prolonged heavy use. The two following cases might depict some of them. Case 1 was a middle-age man who reported three years of intravenous use of mephedrone. He used to binge for several days in a row. Psychotic symptoms appeared after a few months, especially paranoid delusions. Sent to aftercare in a therapeutic community, delusions kept reappearing after prolonged abstinence. A good response to risperidone was observed. Case 2 was a young man who used mephedrone heavily for two years, always snorted. Upon admission to the therapeutic community, the patient reported auditory hallucinations that partially remitted with olanzapine. Both cases showed a good insight and no personality deterioration. Given its similarities to other substances that are known to induce psychotic symptoms, and the increasing consumption of mephedrone around Europe, similar cases are expected in the near future. Conventional antipsychotic treatment seems a reasonable pharmacological approach. PMID- 27399225 TI - Segmental hair testing to disclose chronic exposure to psychoactive drugs. AB - This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg +/- 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 +/- 0.94 ng/mg and 1.50 +/- 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother. PMID- 27399226 TI - Alcoholism and its treatment approach from a citizen perspective. AB - INTRODUCTION: The main objective of the study is to describe alcohol consumption in the general Spanish population, to discover citizens' opinion on their alcohol consumption, on alcoholism and on treatment approaches. METHODS: In 2015 a cross-sectional study was carried out by means of a telephone survey. A representative sample was selected. Participants were asked about their alcohol consumption, their perception of risk regarding their pattern of alcohol consumption, about their opinion on alcoholism, alcohol consequences and the treatment approach. A questionnaire was designed. The Alcohol Use Disorders Identification Test-C was used to define the pattern of alcohol intake. A descriptive and an statistical inference analysis were done. RESULTS: 22.1% were classified as risky drinkers, with a higher proportion in young males. The majority of individuals think that alcoholism is an illness, and more than 75% agree that alcohol has negative consequences on health, social functioning, occupational functioning and family relationships. Furthermore, the perception of risk that citizens have regarding their own drinking pattern is high (37.6%). 67.7% considered that the general practitioner can manage alcoholism, with females and older people believing this most strongly. CONCLUSIONS: Alcohol consumption is very prevalent in the Spanish population, especially in young people (31.8%). The perception of alcohol risk is high. The majority agree with the fact that general practitioners are well prepared for treating alcohol problems. PMID- 27399227 TI - Regulating gambling to prevent addiction: more necessary now than ever. AB - The American Psychiatric Association published the 5th Edition of DSM in May 2013, in which the gambling disorder is included within the category of addictive disorders -a long-standing and recurrent demand from the clinical, social and scientific fields. Nevertheless, the harmful effects of gambling have not been considered by the Government, which is the main area of addiction prevention.The present article is a proposal for the regulation of gambling by the Government through the different levels of the State (national, regional and even local), which has the ultimate goal of preventing gambling addiction. This proposal has been presented to the Chamber of Deputies of the Congress, as part of the Congress-Senate Joint Committee for the Study of Drug Problems. The proposed regulation is based on the evidence provided by scientific studies on the prevention of addiction. PMID- 27399228 TI - Eighty-Eight Percent Directional Guiding of Spin Currents with 90 MUm Relaxation Length in Bilayer Graphene Using Carrier Drift. AB - Electrical control of spin signals and long distance spin transport are major requirements in the field of spin electronics. Here, we report the efficient guiding of spin currents at room temperature in high mobility hexagonal boron nitride encapsulated bilayer graphene using carrier drift. Our experiments, together with modeling, show that the spin relaxation length, that is 7.7 MUm at zero bias, can be tuned from 0.6 to 90 MUm when applying a DC current of ?90 MUA, respectively. Our results also show that we are able to direct spin currents to either side of a spin injection contact. Eighty-eight percent of the injected spins flows to the left when Idc = -90 MUA and eighty-two percent flows to the right when the drift current is reversed. These results show the potential of carrier drift for spin-based logic operations and devices. PMID- 27399229 TI - Human islets contain four distinct subtypes of beta cells. AB - Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin producing beta cells causes diabetes mellitus, a disease that harms millions. Until now, beta cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human beta cells, which we refer to as beta1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the beta cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined beta cell heterogeneity is functionally and likely medically relevant. PMID- 27399230 TI - Estrogen receptor agonists alleviate cardiac and renal oxidative injury in rats with renovascular hypertension. AB - Although endogenous estrogen is known to offer cardiac and vascular protection, the involvement of estrogen receptors in mediating the protective effect of estrogen on hypertension-induced cardiovascular and renal injury is not fully explained. We aimed to investigate the effects of estrogen receptor (ER) agonists on oxidative injury, cardiovascular and renal functions of rats with renovascular hypertension (RVH). Female Sprague-Dawley rats were randomly divided as control and RVH groups, and RVH groups had either ovariectomy (OVX) or sham-OVX. Sham-OVX RVH and OVX-RVH groups received either ERbeta agonist diarylpropiolnitrile (1 mg/kg/day) or ERalpha agonist propyl pyrazole triol (1 mg/kg/day) for 6 weeks starting at the third week following the surgery. At the end of the 9(th) week, systolic blood pressures were recorded, cardiac functions were determined, and the contraction/relaxation responses of aortic rings were obtained. Serum creatinine levels, tissue malondialdehyde, glutathione, superoxide dismutase, catalase levels, and myeloperoxidase activity in heart and kidney samples were analyzed, and Na(+), K(+)-ATPase activity was measured in kidney samples. In both sham-OVX and OVX rats, both agonists reduced blood pressure and reversed the impaired contractile performance of the heart, while ERbeta agonist improved renal functions in both the OVX and non-OVX rats. Both agonists reduced neutrophil infiltration, lipid peroxidation, and elevated antioxidant levels in the heart, but a more ERbeta-mediated protective effect was observed in the kidney. Our data suggest that activation of ERbeta might play a role in preserving the function of the stenotic kidney and delaying the progression of renal injury, while both receptors mediate similar cardioprotective effects. PMID- 27399231 TI - Clinical epidemiology of amyotrophic lateral sclerosis in Liguria, Italy: An update of LIGALS register. AB - Our objectives were: (1) to assess amyotrophic lateral sclerosis (ALS) incidence and its trend over time in Liguria, an Italian north-western region, performing an analysis of data prospectively collected from 1 January 2009 to 31 December 2014; (2) to determine the mean and median survival in the 2009-2014 Ligurian ALS incident cases; and (3) to evaluate the presence of disease prognostic factors. The Liguria Register for ALS (LIGALS) is an ongoing, multicentre prospective register enrolling all ALS incident cases in Liguria. Cases were identified using several concurrent sources. ALS diagnosis was based on El Escorial revised criteria (EEC-R). Two hundred and ninety-eight patients were enrolled in this study. The mean annual crude incidence rate in the 2009-2014 period was 3.11/100,000 population (95% CI 2.77-3.49); the point prevalence at 31 December 2014 was 7.85/100,000 (95% CI 6.54-9.36) population. Survival analysis demonstrated a median survival from symptom onset of 37.0 months (95% CI 32.0 42.0). In conclusion, ALS crude incidence in Liguria is higher compared to other Italian regions. Clinical and epidemiological data are comparable with those of the Italian ALS population. Survival analysis showed that higher age at onset, bulbar onset, definite EEC-R diagnostic category and a shorter diagnostic delay are related with worse outcomes. PMID- 27399232 TI - Alkaloids from the Fungus Penicillium spathulatum as alpha-Glucosidase Inhibitors. AB - Benzomalvin A (1), quinolactacins A1 (2), A2 (3) and B (4), quinolonimide (5), asperphenamate (6), and a new halogenated polyhydroxyanthraquinone, namely 2 chloro-6-[2'(S)-hydroxypropyl]-1,3,8-trihydroxy-anthraquinone (7), were isolated from an organic extract obtained from the solid culture of Penicillium spathulatum B35. Compounds 2 and 3 were isolated as an epimeric mixture, and compound 4 as a racemate. The structure of 7 was elucidated using 1D and 2D NMR, combined with computational methods (density functional theory). Compound 1, the mixture of 2 and 3, racemate 4, and compound 6 inhibited the yeast alpha glucosidase in a concentration-dependent fashion with IC50 values of 383.2, 273.3, 57.3, and 8.3 uM, respectively. The alpha-glucosidase inhibitory properties of 1 were confirmed in vivo with an oral sucrose tolerance test in normal and hyperglycemic mice (p < 0.05). Furthermore, docking studies predicted that the most stable conformers of 1 bind to yeast and mammalian alpha glucosidases with a higher affinity than acarbose. Finally, 1 also showed antihyperalgesic activity when tested in the formalin assay in hyperglycemic mice (p < 0.05). PMID- 27399233 TI - 1HNMR-Based Discriminatory Analysis of Eurycoma longifolia from Different Locations and Establishing a Profile for Primary Metabolites Identification and Quassinoids Quantification. AB - Quassinoids, the major secondary metabolites of Eurycoma longifolia roots, improve male fertility. Hence, it is crucial to investigate their quantitative level in E. longifolia extracts. A profile was established to identify the primary metabolites and major quassinoids, and quantify quassinoids using external calibration curves. Furthermore, the metabolic discrimination of E. longifolia roots from different regions was investigated. The 1H-NMR spectra of the quassinoids, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-beta-D-glycopyranoside were obtained. The 1H-NMR profiles of E. longifolia root aqueous extracts from Perak (n = 30) were obtained and used to identify primary metabolites and the quassinoids. Selangor, Kedah, Terengganu (n = 5 for each), and Perak samples were checked for metabolic discrimination. Hotelling's T2 plot was used to check for outliers. Orthogonal partial least squares discriminant analysis was run to reveal the discriminatory metabolites. Perak samples contained formic, succinic, methylsuccinic, fumaric, lactic, acetic and syringic acids as well as choline, alanine, phenylalanine, tyrosine, alpha glucose, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2 O-beta-D-glycopyranoside. The extracts from other locations contained the same metabolites. The limit of quantification values were 1.96 (eurycomanone), 15.62 (eurycomanol), 3.91 (13,21-dihydroeurycomanone), and 31.25 (eurycomanol-2-O-beta D-glycopyranoside) ppm. The Hotelling's T2 plot revealed no outlier. The orthogonal partial least-squares discriminant analysis model showed that choline, eurycomanol, eurycomanol-2-O-beta-D-glycopyranoside, and lactic and succinic acid levels were different among regions. Terengganu and Perak samples contained higher amounts of eurycomanol and eurycomanol-2-O-beta-D-glycopyranoside, respectively. The current approach efficiently detected E. longifolia root metabolites, quantified the quassinoids, and discriminated E. longifolia roots from different locations. These findings could be applicable to future research on E. longifolia where the higher content of quassinoids is required. PMID- 27399234 TI - A Review of the Medicinal Uses and Pharmacology of Ashitaba. AB - Angelica keiskei Koidzumi, or ashitaba, is a popular botanical medicine in Japan containing diverse bioactive components including prenylated chalcones, linear and angular coumarins, and flavanones. This review provides an overview of the current knowledge of ashitaba metabolites and their biological activities to prioritize future studies. Ashitaba is purported to possess cytotoxic, antidiabetic, antioxidative, anti-inflammatory, antihypertensive, and antimicrobial properties. Although many in vitro studies have been conducted on ashitaba's chemical constituents, the in vivo efficacy and clinical relevance of this plant has yet to be confirmed for most of these activities. Here we describe the chemical composition of ashitaba and present the pharmacological effects of this botanical as supported by the current literature. The experimental results demonstrate promise for the medical use of ashitaba, but considerable work needs to be done to understand the mechanisms of action of its metabolites. Additionally, in vivo and clinical trials as well as additional studies on less abundant bioactive compounds are warranted. PMID- 27399235 TI - Immunoglobulin G4 -related Sclerosing Mastitis: AIRP Best Cases in Radiologic Pathologic Correlation. AB - Editor's Note.-RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year. On the penultimate day of the course, the best case presentation is held at the American Film Institute Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty identifies the best cases, from each organ system, brought by the resident attendees. One or more of the best cases from each of the five courses are then solicited for publication in RadioGraphics. These cases emphasize the importance of radiologic-pathologic correlation in the imaging evaluation and diagnosis of diseases encountered at the institute and its predecessor, the Armed Forces Institute of Pathology (AFIP). PMID- 27399236 TI - Infectious Diseases of the Heart: Pathophysiology, Clinical and Imaging Overview. AB - Myriad infectious organisms can infect the endocardium, myocardium, and pericardium, including bacteria, fungi, parasites, and viruses. Significant cardiac infections are rare in the general population but are associated with high morbidity and mortality as well as increased risk in certain populations, such as the elderly, those undergoing cardiac instrumentation, and intravenous drug abusers. Diagnostic imaging of cardiac infections plays an important role despite its variable sensitivity and specificity, which are due in part to the nonspecific manifestations of the central inflammatory process of infection and the time of onset with respect to the time of imaging. The primary imaging modality remains echocardiography. However, cardiac computed tomography and magnetic resonance (MR) imaging have emerged as the modalities of choice wherever available, especially for diagnosis of complex infectious complications including abscesses, infected prosthetic material, central lines and instruments, and the cryptic manifestations of viral and parasitic diseases. MR imaging can provide functional, morphologic, and prognostic value in a single examination by allowing characterization of inflammatory changes from the acute to chronic stages, including edema and the patterns and extent of delayed gadolinium enhancement. We review the heterogeneous and diverse group of cardiac infections based on their site of primary cardiac involvement with emphasis on their cross-sectional imaging manifestations. Online supplemental material is available for this article. ((c))RSNA, 2016. PMID- 27399237 TI - Material Separation Using Dual-Energy CT: Current and Emerging Applications. AB - Dual-energy (DE) computed tomography (CT) offers the opportunity to generate material-specific images on the basis of the atomic number Z and the unique mass attenuation coefficient of a particular material at different x-ray energies. Material-specific images provide qualitative and quantitative information about tissue composition and contrast media distribution. The most significant contribution of DE CT-based material characterization comes from the capability to assess iodine distribution through the creation of an image that exclusively shows iodine. These iodine-specific images increase tissue contrast and amplify subtle differences in attenuation between normal and abnormal tissues, improving lesion detection and characterization in the abdomen. In addition, DE CT enables computational removal of iodine influence from a CT image, generating virtual noncontrast images. Several additional materials, including calcium, fat, and uric acid, can be separated, permitting imaging assessment of metabolic imbalances, elemental deficiencies, and abnormal deposition of materials within tissues. The ability to obtain material-specific images from a single, contrast enhanced CT acquisition can complement the anatomic knowledge with functional information, and may be used to reduce the radiation dose by decreasing the number of phases in a multiphasic CT examination. DE CT also enables generation of energy-specific and virtual monochromatic images. Clinical applications of DE CT leverage both material-specific images and virtual monochromatic images to expand the current role of CT and overcome several limitations of single-energy CT. ((c))RSNA, 2016. PMID- 27399238 TI - Traumatic Finger Injuries: What the Orthopedic Surgeon Wants to Know. AB - Traumatic finger injuries account for a substantial number of emergency visits every year. Imaging plays an important role in diagnosis and in directing management of these injuries. Although many injuries can be managed conservatively, some require more invasive interventions to prevent complications and loss of function. Accurate diagnosis of finger injuries can often be difficult, given the complicated soft-tissue anatomy of the hand and the diverse spectrum of injuries that can occur. To best serve the patient and the treating physician, radiologists must have a working knowledge of finger anatomy, the wide array of injury patterns that can occur, the characteristic imaging findings of different finger injuries, and the most appropriate treatment options for each type of injury. This article details the intricate anatomy of the hand as it relates to common finger injuries, illustrates the imaging findings of a range of injuries, presents optimal imaging modalities and imaging parameters for the diagnosis of different injury types, and addresses which findings have important management implications for the patient and the orthopedic surgeon. With this fund of knowledge, radiologists will be able to recommend the most appropriate imaging studies, make accurate diagnoses, convey clinically relevant imaging findings to the referring physician, and suggest appropriate follow-up examinations. In this way, the radiologist will help improve patient care and outcomes. Online supplemental material is available for this article. ((c))RSNA, 2016. PMID- 27399240 TI - Commentary on "Multimodality Review of Amyloid-related Diseases of the Central Nervous System". PMID- 27399239 TI - Multimodality Review of Amyloid-related Diseases of the Central Nervous System. AB - Amyloid-beta (Abeta) is ubiquitous in the central nervous system (CNS), but pathologic accumulation of Abeta results in four distinct neurologic disorders that affect middle-aged and elderly adults, with diverse clinical presentations ranging from chronic debilitating dementia to acute life-threatening intracranial hemorrhage. The characteristic imaging patterns of Abeta-related CNS diseases reflect the pathophysiology of Abeta deposition in the CNS. Abeta is recognized as a key component in the neuronal damage that characterizes the pathophysiology of Alzheimer disease, the most common form of dementia. Targeted molecular imaging shows pathologic accumulation of Abeta and tau protein, and fluorine 18 fluorodeoxyglucose positron emission tomography and anatomic imaging allow differentiation of typical patterns of neuronal dysfunction and loss in patients with Alzheimer disease from those seen in patients with other types of dementia. Cerebral amyloid angiopathy (CAA) is an important cause of cognitive impairment and spontaneous intracerebral hemorrhage in the elderly. Hemorrhage and white matter injury seen at imaging reflect vascular damage caused by the accumulation of Abeta in vessel walls. The rare forms of inflammatory angiopathy attributed to Abeta, Abeta-related angiitis and CAA-related inflammation, cause debilitating neurologic symptoms that improve with corticosteroid therapy. Imaging shows marked subcortical and cortical inflammation due to perivascular inflammation, which is incited by vascular Abeta accumulation. In the rarest of the four disorders, cerebral amyloidoma, the macroscopic accumulation of Abeta mimics the imaging appearance of tumors. Knowledge of the imaging patterns and pathophysiology is essential for accurate diagnosis of Abeta-related diseases of the CNS. ((c))RSNA, 2016. PMID- 27399241 TI - Role of PET/CT in Workup of Fever without a Source. AB - Fever without source is a febrile illness without localizing signs or initial obvious cause. Early workup will often include chest radiography and computed tomography (CT) of the abdomen and pelvis, with or without CT of the chest. To evaluate localizing signs or symptoms or to further evaluate findings from initial studies, targeted imaging according to body part can be performed by using radiography, ultrasonography, CT, or magnetic resonance (MR) imaging. Nuclear medicine studies can provide imaging of the whole body and may be helpful when the clinical and conventional imaging workup findings are negative or equivocal in identifying a source of fever. Nuclear medicine studies can be used to detect pathologic changes early in a disease course, even in the absence of an anatomic abnormality. Gallium 67 scintigraphy, indium 111- and technetium 99m labeled leukocyte scintigraphy, and fluorine 18 fluorodeoxyglucose positron emission tomography (PET)/CT studies are all useful in the evaluation of fever, but the radiopharmaceutical cost for PET/CT is much lower than that for radiolabeled leukocyte studies. The increased use of bundled payments for inpatient admissions requires updated cost evaluations for the preferred nuclear medicine study. For inpatients in whom the findings from the initial clinical workup and imaging studies are nondiagnostic, PET/CT examination may be preferable to radiolabeled leukocyte studies because of its high sensitivity and lower cost. Negative findings at PET/CT can be helpful in excluding a suspected site of infection, and positive findings at PET/CT can be helpful in confirming a suspected site of infection or in identifying an unexpected cause of fever. ((c))RSNA, 2016. PMID- 27399242 TI - Cranial Nerve Disorders in Children: MR Imaging Findings. AB - Cranial nerve disorders are uncommon disease conditions encountered in pediatric patients, and can be categorized as congenital, inflammatory, traumatic, or tumorous conditions that involve the cranial nerve itself or propagation of the disorder from adjacent organs. However, determination of the normal course, as well as abnormalities, of cranial nerves in pediatric patients is challenging because of the small caliber of the cranial nerve, as well as the small intracranial and skull base structures. With the help of recently developed magnetic resonance (MR) imaging techniques that provide higher spatial resolution and fast imaging techniques including three-dimensional MR images with or without the use of gadolinium contrast agent, radiologists can more easily diagnose disease conditions that involve the small cranial nerves, such as the oculomotor, abducens, facial, and hypoglossal nerves, as well as normal radiologic anatomy, even in very young children. If cranial nerve involvement is suspected, careful evaluation of the cranial nerves should include specific MR imaging protocols. Localization is an important consideration in cranial nerve imaging, and should cover entire pathways and target organs as much as possible. Therefore, radiologists should be familiar not only with the various diseases that cause cranial nerve dysfunction, and the entire course of each cranial nerve including the intra-axial nuclei and fibers, but also the technical considerations for optimal imaging of pediatric cranial nerves. In this article, we briefly review normal cranial nerve anatomy and imaging findings of various pediatric cranial nerve dysfunctions, as well as the technical considerations of pediatric cranial nerve imaging. Online supplemental material is available for this article. ((c))RSNA, 2016. PMID- 27399243 TI - Pediatric Fibroblastic and Myofibroblastic Tumors: A Pictorial Review. AB - Pediatric fibroblastic and myofibroblastic tumors are a relatively common group of soft-tissue proliferations that are associated with a wide spectrum of clinical behavior. These tumors have been divided into the following categories on the basis of their biologic behavior: benign (eg, myositis ossificans, myofibroma, fibromatosis colli), intermediate-locally aggressive (eg, lipofibromatosis, desmoid fibroma), intermediate-rarely metastasizing (eg, inflammatory myofibroblastic tumors, infantile fibrosarcoma, low-grade myofibroblastic sarcoma), and malignant (eg, fibromyxoid sarcoma, adult fibrosarcoma). Imaging has a key role in the evaluation of lesion origin, extent, and involvement with adjacent structures, and in the treatment management and postresection surveillance of these tumors. The imaging findings of these tumors are often nonspecific. However, certain imaging features, such as low or intermediate signal intensity on T2-weighted magnetic resonance images and extension along fascial planes, support the diagnosis of a fibroblastic or myofibroblastic tumor. In addition, certain tumors have characteristic imaging findings (eg, multiple subcutaneous or intramuscular lesions in infantile myofibromatosis, plaquelike growth pattern of Gardner fibroma, presence of adipose tissue in lipofibromatosis) or characteristic clinical manifestations (eg, great toe malformations in fibrodysplasia ossificans fibroma, neonatal torticollis in fibromatosis colli) that suggest the correct diagnosis. Knowledge of the syndrome associations of some of these tumors-for example, the association between familial adenomatous polyposis syndrome and both Gardner fibroma and desmoid fibromatosis, and that between nevoid basal cell carcinoma syndrome and cardiac fibroma-further facilitate a diagnosis. The recognition of key imaging findings can help guide treatment management and help avoid unnecessary intervention in cases of benign lesions such as myositis ossificans and fibromatosis colli. In this article, we describe the various types of fibroblastic and myofibroblastic tumors in children and the characteristic clinical manifestations, imaging features, and growth patterns of these neoplasms all of which aid in the appropriate radiologic assessment and management of these lesions. ((c))RSNA, 2016. PMID- 27399244 TI - Dual-Energy Spectral CT: Various Clinical Vascular Applications. AB - Single-source dual-energy (DE) computed tomography (CT) with fast switching of tube voltage allows projection-based image reconstruction, substantial reduction of beam-hardening effects, reconstruction of accurate monochromatic images and material decomposition images (MDIs), and detailing of material composition by using x-ray spectral information. In vascular applications, DE CT is expected to overcome limitations of standard single-energy CT angiography, including patient exposure to nephrotoxic contrast medium and carcinogenic radiation, insufficient contrast vascular enhancement, interference from metallic and beam-hardening artifacts and severe vessel calcification, and limited tissue characterization and perfusion assessment. Acquisition of low-energy monochromatic images and iodine/water MDIs can reasonably reduce contrast agent dose and improve vessel enhancement. Acquisition of virtual noncontrast images, such as water/iodine MDIs, can reduce overall radiation exposure by replacing true noncontrast CT in each examination. Acquisition of monochromatic images by using metal artifact reduction software or acquisition of iodine/water MDIs can reduce metal artifacts with preserved or increased vessel contrast, and subtraction of monochromatic images between two energy levels can subtract coils composed of dense metallic materials. Acquisition of iodine/calcium (ie, hydroxyapatite) MDIs permits subtraction of vessel calcification and improves vessel lumen delineation. Sensitive detection of lipid-rich plaque can be achieved by using fat/water MDIs, the spectral Hounsfield unit curve (energy level vs CT attenuation), and a histogram of effective atomic numbers included in an image. Various MDIs are useful for accurate differentiation among materials with high attenuation values, including contrast medium, calcification, and fresh hematoma. Iodine/water MDIs are used to assess organ perfusion, such as in the lungs and myocardium. Understanding these DE CT techniques enhances the value of CT for vascular applications. ((c))RSNA, 2016. PMID- 27399245 TI - Postoperative Imaging after Surgical Repair for Pelvic Floor Dysfunction. AB - Pelvic floor dysfunction encompasses an extremely common set of conditions, with various surgical and nonsurgical treatment options. Surgical options include injection of urethral bulking agents, native tissue repair with or without bioabsorbable or synthetic graft material, placement of synthetic midurethral slings or use of vaginal mesh kits, and mesh sacrocolpopexy procedures. Numerous different synthetic products with varied imaging appearances exist, and some of these products may be difficult to identify at imaging. Patients often present with recurrent or new symptoms after surgery; and depending on the presenting complaint and the nature of the initial intervention, imaging with ultrasonography (US), magnetic resonance (MR) imaging, voiding cystourethrography, or computed tomography (CT) may be indicated. US and MR imaging can both be used to image urethral bulking agents; US is often used to follow potential changes in bulking agent volume with time. Compared with MR imaging, US depicts midurethral slings better in the urethrovaginal space, and MR imaging is better than US for depiction of the arms in the retropubic space and obturator foramen. Mesh along the vaginal wall may be depicted with both US and MR imaging; however, the distal arms of the mesh traversing the sacrospinous ligaments or within the ischiorectal fossae (ischioanal fossae) are better depicted with MR imaging. Scarring can mimic slings and mesh at both US and MR imaging. MR imaging is superior to US for depiction of sacrocolpopexy mesh and associated complications. Voiding cystourethrography and CT are used less commonly because they rarely allow direct depiction of implanted material. Online supplemental material is available for this article. ((c))RSNA, 2016. PMID- 27399246 TI - Congenital Embryonic Arterial and Skeletal Dysgeneses. PMID- 27399247 TI - Tracheobronchial Branching Abnormalities: Lobe-based Classification Scheme Erratum. PMID- 27399248 TI - High-resolution arrays reveal burden of copy number variations on Parkinson disease genes associated with increased disease risk in random cohorts. AB - BACKGROUND: Parkinson disease (PD) is a neurological disease responsible for a considerable rate of mortality and morbidity in the society. Since the symptoms of the disease appear much later than the actual onset of neuron degeneration, a majority of cases remain undiagnosed until the manifestation of the symptoms. OBJECTIVES: In order to investigate the existence of such susceptibility in the population, we analyzed Copy Number Variation (CNV) influences on PD genes in 1715 individuals from 12 different populations. RESULTS: Overall, 16 CNV-PD genes, 3 known to be causal and 13 associated, were found to be significantly enriched. PARK2, was under heavy burden with ~1% of the population containing CNV in the exonic region. The impact of these genes on the genome and disease pathway was analyzed using several genome analysis tools. Protein interaction network of CNV-PD genes revealed a complex interaction of molecules forming a major hub by the alpha-Synuclein, whose direct interactors, LRRK2, PARK2 and ATP13A2 are under CNV influence. CONCLUSIONS: We hypothesize that CNVs may not be the initiating event in the pathogenesis of PD and remain latent until additional secondary hits are acquired and also propose novel genes that may fall under the PD pathway which contribute in pathogenesis. PMID- 27399249 TI - Enoyl acyl carrier protein reductase inhibitors: an updated patent review (2011 - 2015). AB - INTRODUCTION: Enoyl-(acyl-carrier-protein) reductase (ENR) is a limiting step enzyme in the Fatty Acid Synthase II system. In mammals, there is no homologue to ENR, which makes it an optimal candidate target for selective anti-infective drugs. Up-to-date, only two ENR inhibitors are used in clinical practice. AREA COVERED: This review is a survey on important patents on low molecular weight compounds with ENR inhibiting activity published in 2011-2015. Common patent databases (SciFinder, esp@cenet, WIPO) were used to locate patent applications on the proposed topic and in the timespan of 2011-2015. EXPERT OPINION: In 2011 2015, we have observed patents in previously known structural groups of diphenyl ethers and acrylamides as well as new structural classes, often identified by high-throughput screening campaigns. The spectrum of activity of applied derivatives covers significant bacteria, mycobacteria, and apicomplexan parasites (Plasmodia and Toxoplasma). Good news from research of ENR inhibitors: a) four selective anti-staphylococcal compounds applied in 2011-2015 or earlier were pushed to Phase I or Phase II clinical trials and some of them proved safety and tolerability after peroral and/or intravenous administration; b) big pharma companies have renewed their interest in the development of new anti-infective compounds against resistant strains of clinical relevance. PMID- 27399250 TI - Intimately connected: The importance of partner responsiveness for experiencing sexual desire. AB - Sexual desire tends to subside gradually over time, with many couples failing to maintain desire in their long-term relationships. Three studies employed complementary methodologies to examine whether partner responsiveness, an intimacy-building behavior, could instill desire for one's partner. In Study 1, participants were led to believe that they would interact online with their partner. In reality, they interacted with either a responsive or an unresponsive confederate. In Study 2, participants interacted face-to-face with their partner, and judges coded their displays of responsiveness and sexual desire. Study 3 used a daily experiences methodology to examine the mechanisms underlying the responsiveness-desire linkage. Overall, responsiveness was associated with increased desire, but more strongly in women. Feeling special and perceived partner mate value explained the responsiveness-desire link, suggesting that responsive partners were seen as making one feel valued as well as better potential mates for anyone and thus as more sexually desirable. (PsycINFO Database Record PMID- 27399251 TI - Taking the long view: Implications of individual differences in temporal distancing for affect, stress reactivity, and well-being. AB - Recent experimental work demonstrates that temporal distancing from negative experiences reduces distress. Yet two central questions remain: (a) do people differ in the habitual tendency to temporally distance from negative experiences, and if so (b) what implications does this tendency have for well-being? Seven studies explored these questions. Study 1 describes the construction and reliability of the Temporal Distancing Questionnaire, a new measure of individual differences in the tendency to place negative experiences into a broader future time perspective. Study 2 establishes a nomological network around this construct, examining the relationship of temporal distancing to other theoretically related constructs. Study 3 tests whether people high in temporal distancing (i.e., "high temporal distancers") experience greater concurrent well being, including greater positive affect and life satisfaction and lesser negative affect, worry, and depressive symptoms. Study 4 examines whether temporal distancing predicts well-being measured at the daily level, and across time. Finally, Studies 5a-5c explore a key way in which temporal distancing may support psychological well-being-by facilitating more adaptive responses to negative experiences. Our results demonstrate that the tendency to temporally distance from negative experiences predicts a more positive profile of affective experiences and stress-reactivity that may support immediate and longer-term well being. Moreover, many of these findings remained significant when controlling for general reappraisal tendencies. (PsycINFO Database Record PMID- 27399252 TI - Sexual aggression when power is new: Effects of acute high power on chronically low-power individuals. AB - Previous theorists have characterized sexually aggressive behavior as an expression of power, yet evidence that power causes sexual aggression is mixed. We hypothesize that power can indeed create opportunities for sexual aggression but that it is those who chronically experience low power who will choose to exploit such opportunities. Here, low-power men placed in a high-power role showed the most hostility in response to a denied opportunity with an attractive woman (Studies 1 and 2). Chronically low-power men and women given acute power were the most likely to say they would inappropriately pursue an unrequited workplace attraction (Studies 3 and 4). Finally, having power over an attractive woman increased harassment behavior among men with chronic low, but not high, power (Study 5). People who see themselves as chronically denied power appear to have a stronger desire to feel powerful and are more likely to use sexual aggression toward that end. (PsycINFO Database Record PMID- 27399254 TI - Femtomolar Detection of Tau Proteins in Undiluted Plasma Using Surface Plasmon Resonance. AB - The ability to directly detect Tau protein and other neurodegenerative biomarkers in human plasma at clinically relevant concentrations continues to be a significant hurdle for the establishment of diagnostic tests for Alzheimer's disease (AD). In this article, we introduce a new DNA aptamer/antibody sandwich assay pairing and apply it for the detection of human Tau 381 in undiluted plasma at concentrations as low as 10 fM. This was achieved on a multichannel surface plasmon resonance (SPR) platform with the challenge of working in plasma overcome through the development of a tailored mixed monolayer surface chemistry. In addition, a robust methodology was developed involving various same chip control measurements on reference channels to which the detection signal was normalized. Comparative measurements in plasma between SPR and enzyme-linked immunosorbent assay (ELISA) measurements were also performed to highlight both the 1000-fold performance enhancement of SPR and the ability to measure both spiked and native concentrations that are not achievable with ELISA. PMID- 27399253 TI - The multidimensional nature of resilience to spousal loss. AB - Spousal loss can be one of the most devastating events to occur across one's life, resulting in difficulties across different spheres of adjustment; yet, past research on resilience to bereavement has primarily focused on single adjustment indicators. We applied growth mixture modeling to data from 421 participants from the Household Income and Labour Dynamics of Australia Study who experienced spousal loss during the course of the study to examine (a) the extent to which individuals appear to be resilient across 3 indicators of subjective well-being life satisfaction, negative affect, and positive affect, and 2 indicators of health-perceptions of general health and physical functioning-and (b) factors that might promote resilience. Approximately 66%, 19% and 26% individuals showed resilient trajectories, respectively, for life satisfaction, negative affect, and positive affect, whereas 37% and 28% showed resilience, respectively, for perceptions of general health and physical functioning. When we considered all 5 indicators simultaneously, only 8% showed "multidimensional" resilience, whereas 20% showed a non-resilient trajectory across all 5 indicators. The strongest predictors of resilient trajectories were continued engagement in everyday life activities and in social relationships, followed by anticipation that people would comfort them in times of distress. Overall, our findings demonstrate that resilience in the face of spousal bereavement is less common than previously thought. More importantly, they underscore the critical importance of multidimensional approaches while operationalizing doing well in the context of serious life adversities. (PsycINFO Database Record PMID- 27399255 TI - Drug interaction between dabrafenib and immunosuppressive drugs: about one case. AB - Melanoma is a major public health problem. In recent years, it has been shown that melanoma can be characterized by specific oncogenes mutations such as the BRAF mutation, leading to the development of new therapeutic drugs. Dabrafenib is an inhibitor of BRAF, approved as a first-line treatment of metastatic or unresectable stage 3 or 4 melanoma with the BRAF mutation. Few studies have evaluated the drug interaction potential of dabrafenib. This molecule is an enzyme inducer that increases the synthesis of drug-metabolizing enzymes, including CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and UGT enzymes. Accordingly, the plasma concentrations of drugs metabolized by these enzymes are decreased. The decrease in plasma concentrations may cause a reduction or even loss of the clinical effect of these drugs. Many drugs metabolized by these enzymes may be affected, especially midazolam, warfarin, or rifampicin. However, interactions with immunosuppressants have not been described. Everolimus and tacrolimus are two immunosuppressive drugs metabolized by CYP3A4. We report a case of drug interaction between dabrafenib and immunosuppressive drugs (everolimus, tacrolimus), observed in a transplanted heart patient, requiring dosage adjustment of its immunosuppressive treatment to avoid graft rejection. PMID- 27399256 TI - Two Distinct Cylinder Arrangements in Monodomains of a Lyotropic Liquid Crystalline Hexagonal II Phase: Monodomains with Straight Cylinders and Ringed Cylinders in Capillaries. AB - We report a method to produce two different monodomains of an inverse hexagonal II (HII) phase in capillaries. Capillaries filled with glyceryl monooleyl ether (GME) in an inverted micellar phase were soaked in water. After a week, a monodomain of the HII phase with straight cylinders was observed in a capillary with a diameter of 1.0 mm. The axis of the straight cylinders was almost parallel to the capillary axis, and the cylinders were slightly undulated. The lattice constant of the HII phase was 5.85 nm, which indicated the monodomain was fully hydrated. Another monodomain with ringed cylinders was observed in a 0.2 mm diameter capillary. The ringed cylinders aligned to the round capillary wall, where one of the ?10? directions in the hexagonal lattice always faced the wall. The lattice constant was 4.89 nm, from which the estimated water content of the monodomain was almost the lowest reported for the HII phase. The monodomain with ringed cylinders is stabilized by the capillary wall and the low water content. This method to produce specific monodomains is expected to be of benefit for basic and applied research on the HII phase. PMID- 27399257 TI - Structure of the NS3 helicase from Zika virus. AB - Zika virus has emerged as a pathogen of major health concern. Here, we present a high-resolution (1.62-A) crystal structure of the RNA helicase from the French Polynesia strain. The structure is similar to that of the RNA helicase from Dengue virus, with variability in the conformations of loops typically involved in binding ATP and RNA. We identify druggable 'hotspots' that are well suited for in silico and/or fragment-based high-throughput drug discovery. PMID- 27399260 TI - An internal charge transfer-DNA platform for fluorescence sensing of divalent metal ions. AB - Replacement of guanine (G) nucleobases within G-quadruplex (GQ) folding oligonucleotides with push-pull fluorescent 8-arylvinyl-dG residues provides diagnostic emission signalling for divalent metal ion binding. PMID- 27399258 TI - Lipids modulate the conformational dynamics of a secondary multidrug transporter. AB - Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers. PMID- 27399259 TI - Structure of chromatin remodeler Swi2/Snf2 in the resting state. AB - SWI2/SNF2 family proteins regulate a myriad of nucleic acid transactions by sliding, removing and reconstructing nucleosomes in eukaryotic cells. They contain two RecA-like core domains, which couple ATP hydrolysis and DNA translocation to chromatin remodeling. Here we report the crystal structure of Snf2 from the yeast Myceliophthora thermophila. The data show the two RecA-like core domains of Snf2 stacking together and twisting their ATP-binding motifs away from each other, thus explaining the inactivity of the protein in the ground state. We identified several DNA-binding elements, which are fully exposed to solvent, thus suggesting that the protein is poised for its incoming substrate. The catalytic core of Snf2 showed a high chromatin-remodeling activity, which was suppressed by the N-terminal HSA domain. Our findings reveal that the catalytic core of Snf2 is a competent remodeling machine, which rests in an inactive conformation and requires a large conformational change upon activation. PMID- 27399261 TI - Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology. AB - OBJECTIVE: To compare the effect of maternal age on assisted reproductive technology (ART) and spontaneous conception (SC) pregnancies regarding maternal and neonatal complications. DESIGN: Nordic retrospective population-based cohort study. Data from national ART registries were cross-linked with national medical birth registries. SETTING: Not applicable. PATIENT(S): A total of 300,085 singleton deliveries: 39,919 after ART and 260,166 after SC. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hypertensive disorders in pregnancy (HDP), placenta previa, cesarean delivery, preterm birth (PTB; <37 weeks), low birth weight (LBW; <2,500 g), small for gestational age (SGA), and perinatal mortality (>=28 weeks). Adjusted odds ratios (AORs) were calculated. Associations between maternal age and outcomes were analyzed. RESULT(S): The risk of placenta previa (AOR 4.11-6.05), cesarean delivery (AOR 1.18-1.50), PTB (AOR 1.23-2.19), and LBW (AOR 1.44-2.35) was significantly higher in ART than in SC pregnancies for most maternal ages. In both ART and SC pregnancies, the risk of HDP, placenta previa, cesarean delivery, PTB, LBW, and SGA changed significantly with age. The AORs for adverse neonatal outcomes at advanced maternal age (>35 years) showed a greater increase in SC than in ART. The change in risk with age did not differ between ART and SC for maternal outcomes at advanced maternal age. CONCLUSION(S): Having singleton conceptions after ART results in higher maternal and neonatal outcome risks overall, but the impact of age seems to be more pronounced in couples conceiving spontaneously. PMID- 27399262 TI - Me2(CH2Cl)SiCN: Bifunctional Cyanating Reagent for the Synthesis of Tertiary Alcohols with a Chloromethyl Ketone Moiety via Ketone Cyanosilylation. AB - We report a novel bifunctional cyanating reagent, Me2(CH2Cl)SiCN, which paves the way to a one-pot sequential synthesis of tertiary alcohols featuring a chloromethyl ketone moiety via enantioselective ketone cyanosilylation. This method contributes to gram-scale enantioselective total synthesis of the aggregation pheromone of the Colorado potato beetle, (S)-CPB. PMID- 27399263 TI - Cost-Effectiveness of a Model Infection Control Program for Preventing Multi-Drug Resistant Organism Infections in Critically Ill Surgical Patients. AB - BACKGROUND: Interventions to contain two multi-drug-resistant Acinetobacter (MDRA) outbreaks reduced the incidence of multi-drug-resistant (MDR) organisms, specifically methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile in the general surgery intensive care unit (ICU) of our hospital. We therefore conducted a cost-effective analysis of a proactive model infection-control program to reduce transmission of MDR organisms based on the practices used to control the MDRA outbreak. METHODS: We created a model of a proactive infection control program based on the 2011 MDRA outbreak response. We built a decision analysis model and performed univariable and probabilistic sensitivity analyses to evaluate the cost-effectiveness of the proposed program compared with standard infection control practices to reduce transmission of these MDR organisms. RESULTS: The cost of a proactive infection control program would be $68,509 per year. The incremental cost-effectiveness ratio (ICER) was calculated to be $3,804 per aversion of transmission of MDR organisms in a one-year period compared with standard infection control. On the basis of probabilistic sensitivity analysis, a willingness-to-pay (WTP) threshold of $14,000 per transmission averted would have a 42% probability of being cost effective, rising to 100% at $22,000 per transmission averted. CONCLUSIONS: This analysis gives an estimated ICER for implementing a proactive program to prevent transmission of MDR organisms in the general surgery ICU. To better understand the causal relations between the critical steps in the program and the rate reductions, a randomized study of a package of interventions to prevent healthcare-associated infections should be considered. PMID- 27399264 TI - Investigation of the role of alpha-2 adrenergic receptors on prepulse inhibition of acoustic startle reflex in rats. AB - OBJECTIVES: Alpha-2 adrenergic receptors target several behavioral functions. These receptors may connect with the brain pathways mediating sensorimotor gating system that associate with psychoses, and the literature that investigate the relationship between alpha-2 receptors and sensorimotor gating system is very limited and some results are controversial. Thus, we aimed to investigate the role of alpha-2 receptors on prepulse inhibition (PPI) of acoustic startle reflex which is a measure of sensorimotor gating. EXPERIMENTAL DESIGN: Adult male Wistar rats were subjects. PPI was measured as the per cent inhibition of the startle reflex produced by a startling pulse stimulus. The average PPI levels were used in the further analyses. Clonidine (0.03-1 mg/kg), an agonist of alpha-2 receptors, idazoxan (10 mg/kg), an antagonist alpha-2 receptors, and saline were injected to rats intraperitoneally. PPI was evaluated at two different startle intensity levels (78 and 86 dB, respectively). PRINCIPAL OBSERVATIONS: Treatments produced some significant changes on PPI of startle reflex at all two levels of startle intensity. While clonidine (0.06, 0.25, 0.5, and 1 mg/kg) disrupted significantly PPI, idazoxan (10 mg/kg) did not produce any significant effect on PPI. However, pretreatment with idazoxan reversed significantly clonidine-induced disruption of PPI. Neither idazoxan (10 mg/kg) nor clonidine (1 mg/kg) produces any significant change on locomotor activity in naive rats. CONCLUSION: Because idazoxan and clonidine also act through imidazoline receptors, our results suggest that alpha-2 and/or imidazoline receptors are associated with PPI of acoustic startle reflex in rats. Stimulation of these receptors may cause sensorimotor gating disturbances. PMID- 27399265 TI - Premature physeal closure following 13-cis-retinoic acid and prolonged fenretinide administration in neuroblastoma. AB - Retinoid therapy has contributed to improved outcomes in neuroblastoma. Clinical trials of fenretinide report favorable toxicity and disease stabilization in patients with high risk (HR) neuroblastoma. Skeletal effects have been described with other retinoids, but not with fenretinide to date. Two patients with HR, metastatic, refractory neuroblastoma received protracted courses of oral fenretinide for more than 5 years' duration. Both developed premature long bone physeal closure, causing limb length discrepancies; their neuroblastoma remains in remission. The radiographic and clinical findings reported suggest these skeletal abnormalities may be a consequence of treatment with 13-cis-retinoic acid (13cisRA) followed by prolonged oral fenretinide exposure. PMID- 27399266 TI - Control of membrane fouling with the addition of a nanoporous zeolite membrane fouling reducer to the submerged hollow fiber membrane bioreactor. AB - The membrane fouling control via the addition of nanoporous zeolite membrane fouling reducer (Z-MFR) to the submerged membrane bioreactor (MBR) was investigated. Using scanning electron microscopy/energy-dispersive X-ray (SEM/EDX) analysis techniques, the characteristics of fouling on a hollow fiber membrane surface were also analyzed. The addition of Z-MFR to the MBR led to the adsorption of foulants and the flocculation of mixed liquor suspended solids (MLSSs), which resulted in substantially enhancing the membrane filterability. The critical flux values obtained from the sewage mixed liquors of 3400 mg L(-1) at the effective dosage rate of 0.03 mg Z-MFR mg(-1) MLSS was 85 L m(-2) h(-1) (LMH), which was enhanced by 42%. The transmembrane pressure (TMP) variation under the operating conditions of 30 LMH with 3500 mg MLSS L(-1) showed that the addition of Z-MFR extended the time required to reach the critical flux of 0.32 bar by 2.6-fold longer than the control. Thus, due to the hybrid functions of adsorbing foulants and precipitating colloidal substances with the addition of Z MFR, a decrease in the foulant amount and an improvement of sludge flocculation have been attained simultaneously. As a result, the membrane fouling control was achieved effectively with the addition of the Z-MFR. PMID- 27399267 TI - The general results of the RN4CAST survey in Italy. PMID- 27399268 TI - Body image, aging, and identity in women over 50: The Gender and Body Image (GABI) study. AB - We conducted a qualitative study of 1,849 women over age 50 to capture the thoughts, feelings, and attitudes that women at middle age have about their bodies and the experience of aging. Via an open-ended question online survey, four primary themes emerged: (a) the physical and psychological experience of aging; (b) the injustices, inequities, and challenges of aging; (c) the importance of self-care; and (d) a plea for recognition of the need to maintain a contributory role in society. Results highlight the complexities of women's psychological and physical aspects of aging and point toward important topics worthy of further study in this growing population. PMID- 27399269 TI - Local structure orientation descriptor based on intra-image similarity for multimodal registration of liver ultrasound and MR images. AB - PURPOSE: Ultrasound (US)-magnetic resonance (MR) fusion imaging is a profitable tool for image-guided abdominal diagnosis and biopsy. However, the automatic registration of liver US and MR images remains a challenging task. An effective local structure orientation descriptor (LSOD) for use in registering multimodal images is proposed in this study. METHODS: LSOD utilizes a normalized similarity distance vector of intra-image patch pairs to extract intensity change orientations from intensity value changes in a local area. The multimodal similarity measure is then derived using the LSOD vector difference. Experiments were performed on simulated US and liver 2D US-3D MR images from a phantom, two healthy volunteers, and seven patients. RESULTS: Using the LSOD-based method, the root-mean-square target registration errors (RMS-TREs) were 1.76+/-1.90mm/2.03+/ 0.84mm in phantom/clinical experiments. All of the results outperformed those obtained using modality independent neighborhood descriptor (MIND)- and linear correlation of linear combination (LC(2))-based methods (phantom/clinical: 5.23+/ 3.35mm/4.32+/-3.63mm and 9.79+/-5.03mm/6.29+/-3.85mm, respectively). The registration cover range for all subjects of the LSOD-based method was 9.16mm, which was larger than those of the MIND- and LC(2)-based methods (5.06 and 5.12mm, respectively). CONCLUSIONS: The results demonstrated that the LSOD-based registration method could robustly register 2D US and 3D MR images of different liver sections with acceptable accuracy for clinical requirements. This approach is useful for the practical clinical application of the US-MR fusion imaging technique. PMID- 27399270 TI - miR-29b-Loaded Gold Nanoparticles Targeting to the Endoplasmic Reticulum for Synergistic Promotion of Osteogenic Differentiation. AB - Precise control of stem cells, such as human bone marrow-derived mesenchymal stem cells (hMSCs), is critical for the development of effective cellular therapies for tissue engineering and regeneration medicine. Emerging evidence suggests that several miRNAs act as key regulators of diverse biological processes, including differentiation of various stem cells. In this study, we have described a delivery system for miR-29b using PEI-capped gold nanoparticles (AuNPs) to synergistically promote osteoblastic differentiation. The cell proliferation assay revealed that AuNPs and AuNPs/miR-29b exert negligible cytotoxicity to hMSCs and MC3T3-E1 cells. With the assistance of AuNPs as a delivery vector, miR 29b could efficiently enter the cytoplasm and regulate osteogenesis. AuNPs/miR 29b more effectively promoted osteoblast differentiation and mineralization through induced the expression of osteogenesis genes (RUNX2, OPN, OCN, ALP) for the long-term, compared to the widely used commercial transfection reagent, Lipofectamine. With no obvious cytotoxicity, PEI-capped AuNPs showed great potential as an adequate miRNA vector for osteogenesis differentiation. Interestingly, we observed loading of AuNPs as well as AuNPs/miR-29b into the lumen of the endoplasmic reticulum (ER). Our findings collectively suggest that AuNPs, together with miR-29b, exert a synergistic promotory effect on osteogenic differentiation of hMSCs and MC3T3-E1 cells. PMID- 27399271 TI - Comparison of the Performance of Two Different Spectral-Domain Optical Coherence Tomography Angiography Devices in Clinical Practice. AB - PURPOSE: To compare the performance of two different spectral-domain optical coherence tomography angiography (OCTA) devices in clinical practice by evaluating examination execution time and the number of motion artifacts per image. METHODS: Seventy-six patients affected by different ocular diseases and 13 healthy subjects consecutively underwent assessments by two different OCTA devices: AngioPlex (Zeiss Meditec, Inc., Dublin, Calif., USA) and AngioVue (OptoVue, Inc., Fremont, Calif., USA). Two different operators (L.A.D.V. and L.B.) measured execution times, excluded low-quality images, and counted the number of motion artifacts per image. RESULTS: The mean execution time was shorter with AngioPlex than with AngioVue for all subjects (3 min 32 s +/- 1 min 45 s vs. 4 min 35 s +/- 1 min 11 s; p < 0.0001), for the healthy subjects (2 min 31 s +/- 45 s vs. 4 min 1 s +/- 53 s; p = 0.003), and for the patients (3 min 44 s +/- 1 min 48 s vs. 4 min 42 s +/- 1 min 13 s; p < 0.0001). The percentages of available images, low-signal-strength images, and images impossible to analyze of the total acquired images obtained using AngioPlex or AngioVue were 85, 6, and 9% and 56, 29, and 15%, respectively. The mean number of motion artifacts was significantly lower in images obtained using AngioPlex than in images obtained using AngioVue for all patients (6.5 +/- 5.9 vs. 12.6 +/- 8.5; p < 0.0001), for the healthy subjects (6.5 +/- 4.6 vs. 10.9 +/- 7.9; p = 0.0009), and for the patients (6.6 +/- 6.3 vs. 13.1 +/- 8.7; p < 0.0001). There was no correlation between the number of artifacts and execution time or patients' age. CONCLUSION: AngioPlex and AngioVue are useful devices in clinical practice. AngioPlex requires a shorter execution time and provides a higher number of images available for analysis with fewer motion artifacts. PMID- 27399272 TI - Reflections of a cupromaniac. PMID- 27399273 TI - Lysine-specific proteolytic activity responsible for forsythia detaching factor modification. AB - OBJECTIVES: The objective of the present study was to clarify the lysine-specific proteolytic activity derived from periodontal pathogens responsible for Forsythia detaching factor (FDF) modification. DESIGN: The activity responsible for FDF modification in Tannerella forsythia and Porphyromonas gingivalis were evaluated by colorimetric assay using Ac-Arg-Ala-Lys-p-nitroaniline as a substrate. FDF modification in T. forsythia and P. gingivalis were evaluated by Western blotting using recombinant FDF (rFDF) as a substrate. Furthermore, the activity in GCF of 20 patients with periodontitis and 10 healthy subjects was also evaluated by colorimetric assay. Bacteria in subgingival plaque were detected using polymerase chain reaction. RESULTS: The activity of both bacteria in colorimetric assay were 21.35 unit (P. gingivalis) and 3.61 unit (T. forsythia), respectively. Western blot analysis revealed that P. gingivalis was found to efficiently degrade rFDF and T. forsythia partially cleaved rFDF. The activity in GCF from patients with periodontitis (clinically healthy sites: CH, deep bleeding sites: DB and deep non bleeding sites: DNB) was significantly higher than those from healthy subjects (healthy sites: H). Among the patients with periodontitis, the activity from CH was significantly lower than those from DB and DNB. T. forsythia was detected in 68.4% of DNB, in 78.4% of DB and in none of CH. P. gingivalis was detected in 63.2% of DNB, in 84.0% of DB and in 10.5% of CH. No bacterium was detected in healthy subjects. CONCLUSION: The lysine-specific proteolytic activity responsible for FDF modification correlates with the presence of major periodontal pathogens. PMID- 27399274 TI - Alcohol misuse in emerging adulthood: Association of dopamine and serotonin receptor genes with impulsivity-related cognition. AB - Impulsivity predicts alcohol misuse and risk for alcohol use disorder. Cognition mediates much of this association. Genes also account for a large amount of variance in alcohol misuse, with dopamine and serotonin receptor genes of particular interest, because of their role in motivated behavior. The precise psychological mechanisms through which such genes confer risk is unclear. Trait impulsivity conveys risk for alcohol misuse by influencing two distinct domains of cognition: beliefs about the reinforcing effects of alcohol consumption (positive alcohol expectancy) and the perceived ability to resist it (drinking refusal self-efficacy). This study investigated the effect of the dopamine related polymorphism in the DRD2/ANKK1 gene (rs1800497) and a serotonin-related polymorphism in the HTR2A gene (rs6313) on associations between impulsivity, cognition, and alcohol misuse in 120 emerging adults (18-21years). HTR2A predicted lower positive alcohol expectancy, higher refusal self-efficacy, and lower alcohol misuse. However, neither polymorphism moderated the linkages between impulsivity, cognition, and alcohol misuse. This is the first report of an association between HTR2A and alcohol-related cognition. Theoretically-driven biopsychosocial models have potential to elucidate the specific cognitive mechanisms through which distal risk factors like genes and temperament affect alcohol misuse in emerging adulthood. PMID- 27399275 TI - Nonoxido V(IV) Complexes: Prediction of the EPR Spectrum and Electronic Structure of Simple Coordination Compounds and Amavadin. AB - Density functional theory (DFT) calculations of the (51)V hyperfine coupling (HFC) tensor A have been completed for 20 "bare" V(IV) complexes with different donor sets, electric charges, and coordination geometries. Calculations were performed with ORCA and Gaussian software, using functionals BP86, TPSS0, B1LYP, PBE0, B3LYP, B3P, B3PW, O3LYP, BHandHLYP, BHandH, and B2PLYP. Among the basis sets, 6-311g(d,p), 6-311++g(d,p), VTZ, cc-pVTZ, def2-TZVPP, and the "core properties" CP(PPP) were tested. The experimental Aiso and Ai (where i = x or z, depending on the geometry and electronic structure of V(IV) complex) were compared with the values calculated by DFT methods. The results indicated that, based on the mean absolute percentage deviation (MAPD), the best functional to predict Aiso or Ai is the double hybrid B2PLYP. With this functional and the basis set VTZ, it is possible to predict the Aiso and Az of the EPR spectrum of amavadin with deviations of -1.1% and -2.0% from the experimental values. The results allowed us to divide the spectra of nonoxido V(IV) compounds in three types-called "type 1", "type 2", and "type 3", characterized by different composition of the singly occupied molecular orbital (SOMO) and relationship between the values of Ax, Ay, and Az. For "type 1" spectra, Az ? Ax ~ Ay and Az is in the range of (135-155) * 10(-4) cm(-1); for "type 2" spectra, Ax ~ Ay ? Az and Ax ~ Ay are in the range of (90-120) * 10(-4) cm(-1); and for the intermediate spectra of "type 3", Az > Ay > Ax or Ax > Ay > Az, with Az or Ax values in the range of (120-135) * 10(-4) cm(-1). The electronic structure of the V(IV) species was also discussed, and the results showed that the values of Ax or Az are correlated with the percent contribution of V-dxy orbital in the SOMO. Similarly to V(IV)O species, for amavadin the SOMO is based mainly on the V-dxy orbital, and this accounts for the large experimental value of Az (153 * 10(-4) cm(-1)). PMID- 27399276 TI - A hexIM1 on your melanocytes: transcription elongation - the Achilles' heel of melanoma? PMID- 27399277 TI - Perturbation Approaches for Exploring Protein Binding Site Flexibility to Predict Transient Binding Pockets. AB - Simulations of the long-time scale motions of a ligand binding pocket in a protein may open up new perspectives for the design of compounds with steric or chemical properties differing from those of known binders. However, slow motions of proteins are difficult to access using standard molecular dynamics (MD) simulations and are thus usually neglected in computational drug design. Here, we introduce two nonequilibrium MD approaches to identify conformational changes of a binding site and detect transient pockets associated with these motions. The methods proposed are based on the rotamerically induced perturbation (RIP) MD approach, which employs perturbation of side-chain torsional motion for initiating large-scale protein movement. The first approach, Langevin-RIP (L RIP), entails a series of short Langevin MD simulations, each starting with perturbation of one of the side-chains lining the binding site of interest. L-RIP provides extensive sampling of conformational changes of the binding site. In less than 1 ns of MD simulation with L-RIP, we observed distortions of the alpha helix in the ATP binding site of HSP90 and flipping of the DFG loop in Src kinase. In the second approach, RIPlig, a perturbation is applied to a pseudoligand placed in different parts of a binding pocket, which enables flexible regions of the binding site to be identified in a small number of 10 ps MD simulations. The methods were evaluated for four test proteins displaying different types and degrees of binding site flexibility. Both methods reveal all transient pocket regions in less than a total of 10 ns of simulations, even though many of these regions remained closed in 100 ns conventional MD. The proposed methods provide computationally efficient tools to explore binding site flexibility and can aid in the functional characterization of protein pockets, and the identification of transient pockets for ligand design. PMID- 27399278 TI - Behavior and neuroimaging at baseline predict individual response to combined mathematical and working memory training in children. AB - Mathematical performance is highly correlated with several general cognitive abilities, including working memory (WM) capacity. Here we investigated the effect of numerical training using a number-line (NLT), WM training (WMT), or the combination of the two on a composite score of mathematical ability. The aim was to investigate if the combination contributed to the outcome, and determine if baseline performance or neuroimaging predict the magnitude of improvement. We randomly assigned 308, 6-year-old children to WMT, NLT, WMT+NLT or a control intervention. Overall, there was a significant effect of NLT but not WMT. The WMT+NLT was the only group that improved significantly more than the controls, although the interaction NLTxWM was non-significant. Higher WM and maths performance predicted larger benefits for WMT and NLT, respectively. Neuroimaging at baseline also contributed significant information about training gain. Different individuals showed as much as a three-fold difference in their responses to the same intervention. These results show that the impact of an intervention is highly dependent on individual characteristics of the child. If differences in responses could be used to optimize the intervention for each child, future interventions could be substantially more effective. PMID- 27399279 TI - Bridging physiology and economics: Fetal growth and national wealth. PMID- 27399280 TI - Cardiopulmonary resuscitation in hospitalized infants. AB - BACKGROUND: Hospitalized infants requiring cardiopulmonary resuscitation (CPR) represent a high-risk group. Recent data on risk factors for mortality following CPR in this population are lacking. AIMS: We hypothesized that infant demographic characteristics, diagnoses, and levels of cardiopulmonary support at the time of CPR requirement would be associated with survival to hospital discharge following CPR. STUDY DESIGN: Retrospective cohort study. SUBJECTS: All infants receiving CPR on day of life 2 to 120 admitted to 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. OUTCOMES MEASURES: We collected data on demographics, interventions, center volume, and death prior to NICU discharge. We evaluated predictors of death after CPR using multivariable logistic regression with generalized estimating equations to account for clustering of the data by center. RESULTS: Our cohort consisted of 2231 infants receiving CPR. Of these, 1127 (51%) survived to hospital discharge. Lower gestational age, postnatal age, 5-min APGAR, congenital anomaly, and markers of severity of illness were associated with higher mortality. Mortality after CPR did not change significantly over time (Cochran-Armitage test for trend p=0.35). CONCLUSIONS: Mortality following CPR in infants is high, particularly for less mature, younger infants with congenital anomalies and those requiring cardiopulmonary support prior to CPR. Continued focus on at risk infants may identify targets for CPR prevention and improve outcomes. PMID- 27399281 TI - Low Prognostic Nutritional Index (PNI) Predicts Unfavorable Distant Metastasis Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis. AB - BACKGROUND: Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). METHODS: A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool "Cutoff Finder". DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. RESULTS: The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001) as well as multivariate analysis (P<0.001) before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001). The PNI consistently showed a higher AUC value at 1-year (0.780), 3-year (0.793) and 5 year (0.812) in comparison with other prognostic scores. CONCLUSION: PNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients with non-metastatic NPC. PMID- 27399282 TI - Impact of Raw and Bioaugmented Olive-Mill Wastewater and Olive-Mill Solid Waste on the Content of Photosynthetic Molecules in Tobacco Plants. AB - Disposal and reuse of olive-mill wastes are both an economic and environmental problem, especially in countries where the cultivation of olive trees is extensive. Microorganism-based bioaugmentation can be used to reduce the pollutant capacity of wastes. In this work, bioaugmentation was used to reduce the polyphenolic content of both liquid and solid wastes. After processing, bioaugmented wastes were tested on the root development of maize seeds and on photosynthesis-related molecules of tobacco plants. In maize, we found that bioaugmentation made olive-mill wastes harmless for seed germination. In tobacco, we analyzed the content of RuBisCO (ribulose-1,5-bisphosphate carboxylase oxygenase) and of the photosynthetic pigments lutein, chlorophylls, and beta carotene. Levels of RuBisCO were negatively affected by untreated wastewater but increased if plants were treated with bioaugmented wastewater. On the contrary, levels of RuBisCO increased in the case of plants treated with raw olive-mill solid waste. Pigment levels showed dissimilar behavior because their concentration increased if plants were irrigated with raw wastewater or treated with raw olive-mill solid waste. Treatment with bioaugmented wastes restored pigment content. Findings show that untreated wastes are potentially toxic at the commencement of treatment, but plants can eventually adapt after an initial stress period. Bioaugmented wastes do not induce immediate damages, and plants rapidly recover optimal levels of photosynthetic molecules. PMID- 27399283 TI - A Synthetic Route to Chiral Tetrahydropyrroloindoles via Ring Opening of Activated Aziridines with 2-Bromoindoles Followed by Copper-Catalyzed C-N Cyclization. AB - A new synthetic route to nonracemic tetrahydropyrrolo[2,3-b]indoles has been developed via SN2-type ring opening of enantiopure N-activated aziridines with 2 bromoindoles followed by copper-catalyzed C-N cyclization. A series of N activated aziridines and 2-bromoindole derivatives with different substitution patterns were studied to afford the corresponding tetrahydropyrrolo[2,3-b]indoles in good yields and excellent ee (up to 99%). Highly substituted tetrahydropyrrolo[2,3-b]indole was synthesized as a single stereoisomer (de, ee >99%) from enantiopure trans-disubstituted aziridine. PMID- 27399286 TI - Editor's notes. PMID- 27399285 TI - Prospective Associations Between Binge Eating and Psychological Risk Factors in Adolescence. AB - There is evidence that intrapersonal psychological factors might contribute to the development of binge eating. However, studies considering reciprocal effects between risk factors and disordered eating are rare. The present article investigates the nature of the temporal relationships between binge eating and low self-esteem, depressive symptoms, interoceptive deficits, perfectionism, weight/shape concerns, dietary restraint, and the internalization of the societal body ideal in adolescence while taking into account the moderating effects of age and gender. A German population-based sample of 1039 boys and girls from 12 to 19 years of age answered self-report questionnaires on risk factors and eating pathology on 2 measurement points separated by 20 months. Data were analyzed using a cross-lagged panel design. Low self-esteem, interoceptive deficits, weight/shape concerns, and the internalization of the societal body ideal predicted binge eating longitudinally in bivariate analyses. Binge eating predicted later depressive symptoms, whereas perfectionism and dietary restraint were not longitudinally linked to binge eating in either direction. Low self esteem and weight/shape concerns emerged as multivariate predictors of binge eating in girls and boys, respectively. No moderating effects of age were observed. The results suggest that depressive symptoms might rather be a consequence of binge eating than a risk factor, and this underscores that even subclinical eating pathology might be associated with negative psychological outcomes. Central risk factors that should be targeted in prevention programs might be low self-esteem for girls and weight/shape concerns for boys. PMID- 27399287 TI - Letters. PMID- 27399288 TI - Brief reports. PMID- 27399284 TI - HP1 regulates the localization of FANCJ at sites of DNA double-strand breaks. AB - The breast and ovarian cancer predisposition protein BRCA1 forms three mutually exclusive complexes with Fanconi anemia group J protein (FANCJ, also called BACH1 or BRIP1), CtIP, and Abraxas/RAP80 through its BRCA1 C terminus (BRCT) domains, while its RING domain binds to BRCA1-associated RING domain 1 (BARD1). We recently found that the interaction between heterochromatin protein 1 (HP1) and BARD1 is required for the accumulation of BRCA1 and CtIP at sites of DNA double strand breaks. Here, we investigated the importance of HP1 and BARD1-HP1 interaction in the localization of FANCJ together with the other BRCA1-BRCT binding proteins to clarify the separate role of the HP1-mediated pathway from the RNF8/RNF168-induced ubiquitin-mediated pathway for BRCA1 function. FANCJ interacts with HP1gamma in a BARD1-dependent manner, and this interaction was enhanced by ionizing radiation or irinotecan hydrochloride treatment. Simultaneous depletion of all three HP1 isoforms with shRNAs disrupts the accumulation of FANCJ and CtIP, but not RAP80, at double-strand break sites. Replacement of endogenous BARD1 with a mutant BARD1 that is incapable of binding to HP1 also disrupts the accumulation of FANCJ and CtIP, but not RAP80. In contrast, RNF168 depletion disrupts the accumulation of only RAP80, but not FANCJ or CtIP. Consequently, the accumulation of conjugated ubiquitin was only inhibited by RNF168 depletion, whereas the accumulation of RAD51 and sister chromatid exchange were only inhibited by HP1 depletion or disruption of the BARD1-HP1 interaction. Taken together, the results suggest that the BRCA1-FANCJ and BRCA1-CtIP complexes are not downstream of the RNF8/RNF168/ubiquitin pathway, but are instead regulated by the HP1 pathway that precedes homologous recombination DNA repair. PMID- 27399289 TI - Diarrhea in Distance Running. PMID- 27399290 TI - 24th annual meeting of the ACSM. PMID- 27399291 TI - A Sad (and Loud) Song From an Irish Runner. PMID- 27399293 TI - Early Sports Training. PMID- 27399292 TI - Enough for a Lifetime? PMID- 27399294 TI - Early Sports Training: Is It Worth the Price? AB - This controversial subject touches most physicians either in a professional or personal way. The questions can be disturbing-and the answers not always easy to find. In this analysis, the real pressures and risks, and the real abilities of children, are explored. PMID- 27399295 TI - Cme credit quiz. PMID- 27399296 TI - Walking the Perilous Path of the Team Psychologist. PMID- 27399297 TI - An Overlooked Problem: Athletes' Visual Needs. AB - "You didn't keep your eye on the ball," the coach shouts to the split end whom he removes from the game when he drops a pass, or to the quarterback who has just thrown the ball short and into the waiting hands of a defensive halfback. "Where were you looking?" asks the basketball coach of the player who has missed an easy pass under the basket. "Coach, I just didn't see it coming!" is the anguished reply. PMID- 27399298 TI - What to Look For in an Exercise Class Leader. AB - Patients who desire guidance on exercise programs suited to their capacities can make up a sizable segment of the physician's practice. Exercise facilities are widely available, but how does the physician choose the right one? Dr. Oldridge offers keys to judging the quality of this important vehicle for rehabilitation and health maintenance. PMID- 27399299 TI - Seeing Is Performing, Says Optometrist. PMID- 27399300 TI - 'Acupinch' for Muscle Cramps. PMID- 27399301 TI - Adults Play Big Role in Children's Sports. PMID- 27399304 TI - Establishment of a fully automated microtiter plate-based system for suspension cell culture and its application for enhanced process optimization. AB - We developed an automated microtiter plate (MTP)-based system for suspension cell culture to meet the increased demands for miniaturized high throughput applications in biopharmaceutical process development. The generic system is based on off-the-shelf commercial laboratory automation equipment and is able to utilize MTPs of different configurations (6-24 wells per plate) in orbital shaken mode. The shaking conditions were optimized by Computational Fluid Dynamics simulations. The fully automated system handles plate transport, seeding and feeding of cells, daily sampling, and preparation of analytical assays. The integration of all required analytical instrumentation into the system enables a hands-off operation which prevents bottlenecks in sample processing. The modular set-up makes the system flexible and adaptable for a continuous extension of analytical parameters and add-on components. The system proved suitable as screening tool for process development by verifying the comparability of results for the MTP-based system and bioreactors regarding profiles of viable cell density, lactate, and product concentration of CHO cell lines. These studies confirmed that 6 well MTPs as well as 24 deepwell MTPs were predictive for a scale up to a 1000 L stirred tank reactor (scale factor 1:200,000). Applying the established cell culture system for automated media blend screening in late stage development, a 22% increase in product yield was achieved in comparison to the reference process. The predicted product increase was subsequently confirmed in 2 L bioreactors. Thus, we demonstrated the feasibility of the automated MTP-based cell culture system for enhanced screening and optimization applications in process development and identified further application areas such as process robustness. The system offers a great potential to accelerate time-to-market for new biopharmaceuticals. Biotechnol. Bioeng. 2017;114: 113-121. (c) 2016 Wiley Periodicals, Inc. PMID- 27399303 TI - Ephrin-B2 prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity. AB - OBJECTIVE: To demonstrate that ephrin-B2 (the ligand of EphB2 receptor) antagonizes the pathogenic effects of patients' N-methyl-D-aspartate receptor (NMDAR) antibodies on memory and synaptic plasticity. METHODS: One hundred twenty two C57BL/6J mice infused with cerebrospinal fluid (CSF) from patients with anti NMDAR encephalitis or controls, with or without ephrin-B2, were investigated. CSF was infused through ventricular catheters connected to subcutaneous osmotic pumps over 14 days. Memory, behavioral tasks, locomotor activity, presence of human antibodies specifically bound to hippocampal NMDAR, and antibody effects on the density of cell-surface and synaptic NMDAR and EphB2 were examined at different time points using reported techniques. Short- and long-term synaptic plasticity were determined in acute brain sections; the Schaffer collateral pathway was stimulated and the field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus. RESULTS: Mice infused with patients' CSF, but not control CSF, developed progressive memory deficit and depressive-like behavior along with deposits of NMDAR antibodies in the hippocampus. These findings were associated with a decrease of the density of cell-surface and synaptic NMDAR and EphB2, and marked impairment of long-term synaptic plasticity without altering short-term plasticity. Administration of ephrin-B2 prevented the pathogenic effects of the antibodies in all the investigated paradigms assessing memory, depressive-like behavior, density of cell-surface and synaptic NMDAR and EphB2, and long-term synaptic plasticity. INTERPRETATION: Administration of ephrin-B2 prevents the pathogenic effects of anti-NMDAR encephalitis antibodies on memory and behavior, levels of cell-surface NMDAR, and synaptic plasticity. These findings reveal a strategy beyond immunotherapy to antagonize patients' antibody effects. Ann Neurol 2016;80:388-400. PMID- 27399305 TI - Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care. PMID- 27399306 TI - Adapting SHIVs In Vivo Selects for Envelope-Mediated Interferon-alpha Resistance. AB - Lentiviruses are able to establish persistent infection in their respective hosts despite a potent type-I interferon (IFN-I) response following transmission. A number of IFN-I-induced host factors that are able to inhibit lentiviral replication in vitro have been identified, and these studies suggest a role for IFN-induced factors as barriers to cross-species transmission. However, the ability of these factors to inhibit viral replication in vivo has not been well characterized, nor have the viral determinants that contribute to evasion or antagonism of the host IFN-I response. In this study, we hypothesized that the host IFN-I response serves as a strong selective pressure in the context of SIV/HIV chimeric virus (SHIV) infection of macaques and sought to identify the viral determinants that contribute to IFN-I resistance. We assessed the ability of SHIVs encoding HIV-1 sequences adapted by serial passage in macaques versus SHIVs encoding HIV sequences isolated directly from infected individuals to replicate in the presence of IFNalpha in macaque lymphocytes. We demonstrate that passage in macaques selects for IFNalpha resistant viruses that have higher replication kinetics and increased envelope content. SHIVs that encode HIV-1 sequences derived directly from infected humans were sensitive to IFNalpha induced inhibition whereas SHIVs obtained after passage in macaques were not. This evolutionary process was directly observed in viruses that were serially passaged during the first few months of infection-a time when the IFNalpha response is high. Differences in IFNalpha sensitivity mapped to HIV-1 envelope and were associated with increased envelope levels despite similar mRNA expression, suggesting a post-transcriptional mechanism. These studies highlight critical differences in IFNalpha sensitivity between HIV-1 sequences in infected people and those used in SHIV models. PMID- 27399307 TI - Sex differences in the relationship between heavy alcohol use, inhibition and performance monitoring: Disconnect between behavioural and brain functional measures. AB - Previous research has reported mixed evidence of sex differences in the relationship between heavy alcohol use and deficits in behavioural control. Here, we examine sex differences in behavioural and event-related potential (ERP) markers of deficient inhibition. Participants were 71 young adults aged 18-21, who either drank heavily regularly (i.e., four standard drinks on one occasion, at least once a month, n=33, 20 male) or drank heavily less often than this (including never, n=38, 21 male). They completed a stop-signal task while ERPs were recorded. Increases in stop-signal reaction time, the time required to stop a response, were related to heavy drinking only in female participants. P3 amplitude, ERN amplitude and ERN latency did not display a significant interaction between group and sex. Heavy drinkers, regardless of sex, displayed a marginally larger successful>failed effect for P3 amplitude, and a marginally smaller error-related negativity. An apparent disconnect exists in behavioural and psychophysiological measures of sex differences in the relationship between heavy alcohol consumption and inhibitory processing; male heavy drinkers display only psychophysiological but not behavioural deficits, while female heavy drinkers display both. Future research may determine whether sex differences are apparent for other substances besides alcohol. PMID- 27399308 TI - The relationship between self-referential processing-related brain activity and anhedonia in patients with schizophrenia. AB - Despite the possible relationship between impaired self-referential processing and anhedonia, it has not yet been investigated. This study investigated an abnormality in brain activation associated with self-referential processing and its relationship with anhedonia in schizophrenia, specifically in self-related brain regions of interest. Twenty patients with schizophrenia and 25 controls underwent functional magnetic resonance imaging while rating the degree of relevance between faces (self, familiar other, or unfamiliar other) and words (positive, negative, or neutral). Brain activation in self-related regions, including the ventral and dorsal medial prefrontal cortices, anterior cingulate cortex (ACC), posterior cingulate cortex, precuneus, and insula, were compared between groups and their correlations with anhedonia level were calculated. Compared to controls, patients were less likely to rate negative words as irrelevant for the self face. Patients showed significantly increased activation in the ACC and precuneus compared to controls, irrespective of conditions. ACC activity in the self-neutral word condition was positively correlated with anhedonia score in patients. These results suggest that patients with schizophrenia may have an abnormality in the self-related cortical midline structures and particularly, abnormal ACC activation may be involved in anhedonia. Disrupted self-referential processing may be a possible cause of anhedonia in schizophrenia. PMID- 27399309 TI - Global and local grey matter reductions in boys with ADHD combined type and ADHD inattentive type. AB - Attention-deficit/hyperactivity disorder (ADHD) has reliably been associated with global grey matter reductions but local alterations are largely inconsistent with perhaps the exception of the caudate nucleus. The aim of this study was to examine local and global brain volume differences between typically developing children (TD) and children with a diagnosis of ADHD. We also addressed whether these parameters would differ between children with the ADHD-combined type (ADHD C) and those with the ADHD-inattentive type (ADHD-I). Using an ROI approach caudate volume differences were also examined. 79 boys between the ages of 8 and 17 participated in the study. Of those 33 met diagnostic criteria for the ADHD-C and 15 for the ADHD-I subtype. 31 boys were included in the TD group. Structural magnetic resonance imaging data were analysed using voxel-based morphometry. The ADHD group had significantly lower global and local grey matter volumes within clusters in the bilateral frontal, right parietal and right temporal regions compared to TD. A significant group by age interaction was found for right caudate nucleus volume. No differences between the ADHD-C and ADHD-I groups were found. Right caudate nucleus volume and age are more strongly related in ADHD than in TD consistent with previous research. PMID- 27399311 TI - Increased survival and decreased recurrence in colorectal cancer patients diagnosed in a screening programme. AB - INTRODUCTION: Population-based screening programmes for colorectal cancer (CRC) allow an early diagnosis, even before the onset of symptoms, but there are few studies and none in Spain on the influence they have on patient survival. The aim of the present study is to show that patients receiving surgery for CRC following diagnosis via a screening programme have a higher survival and disease-free survival rate than those diagnosed in the symptomatic stage. MATERIAL AND METHODS: Prospective study of all the patients undergoing programmed surgery for CRC at the JM Morales Meseguer Hospital in Murcia (Spain) between 2004 and 2010. The patients were divided into two groups: (a) those diagnosed through screening (125 cases); and (b) those diagnosed in the symptomatic stage (565 cases). Survival and disease-free survival were analysed and compared for both groups using the Mantel method. RESULTS: The screen-detected CRC patients show a higher rate of survival (86.3% versus 72.1% at 5 years, p<0.05) and a lower rate of tumour recurrence (73.4% versus 88.3% at 5 years, p<0.05). CONCLUSIONS: Population-based screening for CRC is an effective strategic measure for reducing mortality specific to this neoplasia. PMID- 27399310 TI - Community Knowledge, Perceptions, and Practices Associated with Urogenital Schistosomiasis among School-Aged Children in Zanzibar, United Republic of Tanzania. AB - BACKGROUND: On the Zanzibar islands, United Republic of Tanzania, elimination of urogenital schistosomiasis is strived for in the coming years. This qualitative study aimed to better understand community knowledge, perceptions, and practices associated with schistosomiasis among school-aged children on Unguja and Pemba islands, in order to inform the development of behavior change interventions contributing to eliminate urogenital schistosomiasis. METHODOLOGY: In 2011, we conducted 35 children's discussion groups, 41 in-depth interviews with parents and teachers, and 5 focus group discussions with community members in Zanzibar. Using a modified-grounded theory approach, we transcribed and coded the narrative data followed by thematic analysis of the emergent themes. PRINCIPAL FINDINGS: Urogenital schistosomiasis is a common experience among children in Zanzibar and typically considered a boys' disease. Children engage in multiple high-risk behaviors for acquiring schistosomiasis because of poor knowledge on disease transmission, lack of understanding on severity of disease-associated consequences, and lack of alternative options for water related activities of daily living and recreational play. Local primary school teachers had little to no training about the disease and no teaching tools or materials for students. CONCLUSIONS/SIGNIFICANCE: Conducting activities in open natural freshwater contaminated by S. haematobium larvae compromises the health of school-aged children in Zanzibar. The perception of urogenital schistosomiasis as a minor illness rather than a serious threat to a child's well-being contributes to the spread of disease. Understanding community perceptions of disease along with the barriers and facilitators to risk reduction behaviors among children can inform health promotion activities, campaigns, and programs for the prevention, control, and elimination of urogenital schistosomiasis in Zanzibar. PMID- 27399312 TI - Data quality at the Singapore Cancer Registry: An overview of comparability, completeness, validity and timeliness. AB - AIM: To provide a comprehensive evaluation of the quality of the data at the Singapore Cancer Registry (SCR). METHODS: Quantitative and semi-quantitative methods were used to assess the comparability, completeness, accuracy and timeliness of data for the period of 1968-2013, with focus on the period 2008 2012. RESULTS: The SCR coding and classification systems follow international standards. The overall completeness was estimated at 98.1% using the flow method and 97.5% using the capture-recapture method, for the period of 2008-2012. For the same period, 91.9% of the cases were morphologically verified (site-specific range: 40.4-100%) with 1.1% DCO cases. The under-reporting in 2011 and 2012 due to timely publication was estimated at 0.03% and 0.51% respectively. CONCLUSION: This review shows that the processes in place at the SCR yields data which are internationally comparable, relatively complete, valid, and timely, allowing for greater confidence in the use of quality data in the areas of cancer prevention, treatment and control. PMID- 27399313 TI - Endoscopic Instruments and Electrosurgical Unit for Colonoscopic Polypectomy. AB - Colorectal polypectomy is an effective method for prevention of colorectal cancer. Many endoscopic instruments have been used for colorectal polypectomy, such as snares, forceps, endoscopic clips, a Coagrasper, retrieval net, injector, and electrosurgery generator unit (ESU). Understanding the characteristics of endoscopic instruments and their proper use according to morphology and size of the colorectal polyp will enable endoscopists to perform effective polypectomy. I reviewed the characteristics of endoscopic instruments for colorectal polypectomy and their appropriate use, as well as the basic principles and settings of the ESU. PMID- 27399314 TI - Magnetic fields, radicals and cellular activity. AB - Some effects of low-intensity magnetic fields on the concentration of radicals and their influence on cellular functions are reviewed. These fields have been implicated as a potential modulator of radical recombination rates. Experimental evidence has revealed a tight coupling between cellular function and radical pair chemistry from signaling pathways to damaging oxidative processes. The effects of externally applied magnetic fields on biological systems have been extensively studied, and the observed effects lack sufficient mechanistic understanding. Radical pair chemistry offers a reasonable explanation for some of the molecular effects of low-intensity magnetic fields, and changes in radical concentrations have been observed to modulate specific cellular functions. Applied external magnetic fields have been shown to induce observable cellular changes such as both inhibiting and accelerating cell growth. These and other mechanisms, such as cell membrane potential modulation, are of great interest in cancer research due to the variations between healthy and deleterious cells. Radical concentrations demonstrate similar variations and are indicative of a possible causal relationship. Radicals, therefore, present a possible mechanism for the modulation of cellular functions such as growth or regression by means of applied external magnetic fields. PMID- 27399315 TI - Successful Treatment of Cerebral Aspergillosis in a Patient with Acquired Immune Deficiency Syndrome. AB - We report a case of a patient with AIDS and a brain abscess caused by aspergillus, who underwent neurosurgical excision of the lesion and received subsequent therapy with voriconazole. The patient suffered from intracranial hypertension and visual disorders. PMID- 27399320 TI - Reply to Dickson-Lowe et al. PMID- 27399321 TI - Unlocking the molecular mechanisms of antipsychotics - a new frontier for discovery. AB - Despite the use of antipsychotics to treat schizophrenia for the last several decades, little was understood about their molecular mechanisms of action. In this review, we discuss recent studies that have helped elucidate mechanisms of action of antipsychotics and their potential interplay with genetic, metabolomic, proteomic, and other cellular process-related discoveries in schizophrenia pathology. We also highlight genes that have been identified in multiple studies in both schizophrenia patients and in antipsychotic action that are related to glucose and cellular metabolism, the cytoskeleton, protein synthesis, cell adhesion and synaptic activity. Though some questions of antipsychotic mechanisms of action, such as primary versus off-target effects, remain, the recent gains in understanding how to treat schizophrenia at the molecular level are promising. We propose that these recent insights provide a new and more complete landscape for drug discovery and patient biomarker development. PMID- 27399323 TI - Statement of retraction. PMID- 27399322 TI - Chest Pain in a Patient With Left Bundle Branch Block. PMID- 27399324 TI - Time to Eliminate the Step 2 Clinical Skills Examination for US Medical Graduates. PMID- 27399325 TI - Electrical Transport Properties of Polymorphic MoS2. AB - The engineering of polymorphs in two-dimensional layered materials has recently attracted significant interest. Although the semiconducting (2H) and metallic (1T) phases are known to be stable in thin-film MoTe2, semiconducting 2H-MoS2 is locally converted into metallic 1T-MoS2 through chemical lithiation. In this paper, we describe the observation of the 2H, 1T, and 1T' phases coexisting in Li treated MoS2, which result in unusual transport phenomena. Although multiphase MoS2 shows no transistor-gating response, the channel resistance decreases in proportion to the temperature, similar to the behavior of a typical semiconductor. Transmission electron microscopy images clearly show that the 1T and 1T' phases are randomly distributed and intervened with 2H-MoS2, which is referred to as the 1T and 1T' puddling phenomenon. The resistance curve fits well with 2D-variable range-hopping transport behavior, where electrons hop over 1T domains that are bounded by semiconducting 2H phases. However, near 30 K, electrons hop over charge puddles. The large temperature coefficient of resistance (TCR) of multiphase MoS2, -2.0 * 10(-2) K(-1) at 300 K, allows for efficient IR detection at room temperature by means of the photothermal effect. PMID- 27399326 TI - Free-breathing Sparse Sampling Cine MR Imaging with Iterative Reconstruction for the Assessment of Left Ventricular Function and Mass at 3.0 T. AB - Purpose To prospectively evaluate the accuracy of left ventricle (LV) analysis with a two-dimensional real-time cine true fast imaging with steady-state precession (trueFISP) magnetic resonance (MR) imaging sequence featuring sparse data sampling with iterative reconstruction (SSIR) performed with and without breath-hold (BH) commands at 3.0 T. Materials and Methods Ten control subjects (mean age, 35 years; range, 25-56 years) and 60 patients scheduled to undergo a routine cardiac examination that included LV analysis (mean age, 58 years; range, 20-86 years) underwent a fully sampled segmented multiple BH cine sequence (standard of reference) and a prototype undersampled SSIR sequence performed during a single BH and during free breathing (non-BH imaging). Quantitative analysis of LV function and mass was performed. Linear regression, Bland-Altman analysis, and paired t testing were performed. Results Similar to the results in control subjects, analysis of the 60 patients showed excellent correlation with the standard of reference for single-BH SSIR (r = 0.93-0.99) and non-BH SSIR (r = 0.92-0.98) for LV ejection fraction (EF), volume, and mass (P < .0001 for all). Irrespective of breath holding, LV end-diastolic mass was overestimated with SSIR (standard of reference: 163.9 g +/- 58.9, single-BH SSIR: 178.5 g +/- 62.0 [P < .0001], non-BH SSIR: 175.3 g +/- 63.7 [P < .0001]); the other parameters were not significantly different (EF: 49.3% +/- 11.9 with standard of reference, 48.8% +/- 11.8 with single-BH SSIR, 48.8% +/- 11 with non-BH SSIR; P = .03 and P = .12, respectively). Bland-Altman analysis showed similar measurement errors for single BH SSIR and non-BH SSIR when compared with standard of reference measurements for EF, volume, and mass. Conclusion Assessment of LV function with SSIR at 3.0 T is noninferior to the standard of reference irrespective of BH commands. LV mass, however, is overestimated with SSIR. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27399327 TI - Percutaneous CT-guided Radiofrequency Ablation for Lymph Node Oligometastases from Hepatocellular Carcinoma: A Propensity Score-matching Analysis. AB - Purpose To assess the effectiveness and safety of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for lymph node (LN) oligometastases from hepatocellular carcinoma (HCC). Materials and Methods This retrospective study was approved by the institutional ethics committee, and all patients provided written informed consent. From January 2004 to December 2013, 119 consecutive patients with HCC and LN oligometastases (115 men [mean age, 51.3 years; age range, 16-83 years] and four women [mean age, 38.2 years; age range, 23-47 years]) were included in this study. A matched cohort composed of 46 patients from each group was selected after adjustment with propensity score matching. The median follow-up time was 14.0 months in the RFA group and 13.8 months in the non-RFA group. The overall survival (OS), local control rate, and complications were evaluated. Survival curves were constructed with the Kaplan Meier method and compared by using the log-rank test. Results Eighty-seven patients had LN metastases located in the regional site, and 32 patients had LN metastases in the distant site. No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. The RFA group showed higher 6-month and 1-year OS rates compared with the non-RFA group (87.0% and 58.3% vs 62.4% and 17.9%, respectively; P = .001). The 3-month local control rate after RFA was 84.4%, including complete response in 71.1% of patients and partial response in 13.3%. The complications of RFA were short-term abdominal pain and self-limited local hematoma, which occurred in 10 patients (21.7%) and five patients (10.9%), respectively. Conclusion Percutaneous CT-guided RFA may be a safe and effective treatment for the LN oligometastases generated by HCC. (c) RSNA, 2016. PMID- 27399328 TI - Protective Effect of Low-Intensity Pulsed Ultrasound on Memory Impairment and Brain Damage in a Rat Model of Vascular Dementia. AB - Purpose To investigate the neuroprotective effects of low-intensity pulsed (LIP) ultrasound on memory impairment and central nervous system injury in a rat model of vascular dementia. Materials and Methods All animal experiments were approved by the animal care and use committee and adhered to experimental animal care guidelines. A 1.0-MHz focused ultrasound transducer was used to stimulate the brain noninvasively with 50-msec bursts at a 5% duty cycle, repetition frequency of 1 Hz, and spatial peak temporal average intensity of 528 mW/cm2. LIP ultrasound treatment was performed daily with triple sonications in each hemisphere. The duration of each sonicaton was 5 minutes, with a 5-minute interval between each sonication. Permanent bilateral common carotid artery occlusion (BCCAO) was used as a model of vascular dementia. After 2 weeks of LIP ultrasound, neuroprotective effects of LIP ultrasound were evaluated with behavioral analysis, including the passive avoidance task and elevated plus maze. Myelin content was detected with carbon 11 (11C) Pittsburgh compound B (PIB). Brain sections were stained with hematoxylin-eosin and Luxol fast blue. Two-way analysis of variance and Student t test were used for statistical analyses, with a significance level of .05. Results Protein expressions of brain-derived neurotrophic factor (BDNF) in the BCCAO rats treated with LIP ultrasound were significantly higher than those in BCCAO rats (1.1 +/- 0.0 vs 0.8 +/- 0.1, P < .05). BCCAO rats exhibited neuronal damage and demyelination. Compared with the BCCAO group, 11C PIB accumulation in the BCCAO rats treated with LIP ultrasound was significantly (P < .05) increased by 67.4% and 203.0% in the hippocampus and corpus callosum, respectively. Hematoxylin-eosin staining showed that neuronal injury in the hippocampal cornu ammonis 1 region was alleviated with LIP ultrasound. Luxol fast blue staining of the corpus callosum was significantly greater in the BCCAO rats treated with LIP ultrasound than in the untreated BCCAO rats (mean, 94.5% +/- 2.3 [standard error] vs 86.6% +/- 1.0; P < .05). Moreover, LIP ultrasound stimulation significantly improved learning and memory abilities and morphology in rats with vascular dementia compared with rats with untreated vascular dementia (P < .05). Conclusion These results suggest LIP ultrasound stimulation protects against brain injury in the hippocampus and corpus callosum in rats with vascular dementia. The beneficial effect of LIP ultrasound may be partly induced by upregulation of protein expression of BDNF. (c) RSNA, 2016. PMID- 27399329 TI - 2016: Reviewing for Radiology-Reporting Guidelines and Why We Use Them. AB - It is our hope that increased use and awareness of guideline criteria will allow for the manuscripts, at the time of submission, to be more complete and aid our reviewers in better understanding, and thus critiquing, the methodology and results of submissions they receive. Online supplemental material is available for this article. PMID- 27399330 TI - Increased plasma lactate level is associated with subclinical cardiovascular damage in patient with non-dipping hypertension. AB - OBJECTIVE: To evaluate the difference of plasma lactate level between dipping and non-dipping hypertension, and to investigate the effects of lactate on subclinical cardiovascular damages in dipping and non-dipping hypertension. METHODS: According to 24 h ambulatory blood pressure monitoring, 236 patients with dipping and 152 with non-dipping hypertension were included. Clinical characteristics were collected and compared between dipping and non-dipping groups. Left ventricle hypertrophy (LVH) and N-terminal pro-B type natriuretic peptide (NT-proBNP) level were used to evaluate subclinical cardiovascular damage. Multivariate regression analysis was performed to evaluate the relationship between lactate and LVH and NT-proBNP elevation. RESULTS: Compared to dipping hypertension, plasma levels of lactate and NT-proBNP in non-dipping hypertension group were significantly higher. Moreover, the value of left ventricle mass index to height (LVMI/height) was also significantly higher in non dipping group, and the percentage of patient with LVH was also higher in non dipping group (36.8% vs. 28.9%, P < 0.05). Multivariate regression analysis revealed that in non-dipping group, after fully adjustment, the associations between lactate with LVH and NT-proBNP remained significant, with odds ratio (OR) of 1.18 (95% confidence interval [CI] of 1.13-1.24) in LVH and OR of 1.16 in NT proBNP (95% CI of 1.10-1.23), respectively. Nonetheless, the associations between lactate with LVH and NT-proBNP elevation in dipping group were diminished to statistical nonsignificance. CONCLUSION: Plasma lactate level in non-dipping hypertension is significantly higher than dipping hypertension, and this difference may be the potential mechanism non-dipping hypertension contributes to greater targeted organ damage. PMID- 27399331 TI - NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes. AB - The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies. PMID- 27399332 TI - Inhibition of MAPK pathway is essential for suppressing Rheb-Y35N driven tumor growth. AB - Rheb is a Ras family GTPase, which binds to and activates mammalian target of rapamycin complex 1 (mTORC1) when GTP loaded. Recently, cancer genome sequencing efforts have identified recurrent Rheb Tyr35Asn mutations in kidney and endometrial carcinoma. Here we show that Rheb-Y35N causes not only constitutive mTORC1 activation, but sustained activation of the MEK-ERK pathway in a TSC1/TSC2/TBC1D7 protein complex and mTORC1-independent manner, contributing to intrinsic resistance to rapamycin. Rheb-Y35N transforms NIH3T3 cells, resulting in aggressive tumor formation in xenograft nude mice, which could be suppressed by combined treatment with rapamycin and an extracellular signal-regulated kinase (ERK) inhibitor. Furthermore, Rheb-Y35N inhibits AMPKalpha activation in response to nutrient depletion or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), leading to attenuated phosphorylation of BRAF-S729 and retained mitogen-activated protein kinase (MAPK) activation. Finally, we demonstrate that Rheb-WT can bind AMPK to facilitate AMPK activation, whereas Rheb-Y35N competitively binds AMPK, impairing AMPK phosphorylation. In summary, our findings indicate that Rheb-Y35N is a dominantly active tumor driver that activates both mTORC1 and MAPK to promote tumor growth, suggesting a combination of mTORC1 and MAPK inhibitors may be of therapeutic value in patients whose cancers sustain this mutation. PMID- 27399333 TI - Overproduction of IGF-2 drives a subset of colorectal cancer cells, which specifically respond to an anti-IGF therapeutic antibody and combination therapies. AB - Colorectal cancer (CRC) is a heterogeneous disease with a broad spectrum of genetic and epigenetic changes. A comprehensive molecular characterization of CRC by The Cancer Genome Atlas Network detected the overexpression of the insulin like growth factor 2 (IGF2) gene, encoding a ligand for the insulin-like growth factor 1 receptor (IGF-1R), in a subset of CRC tumors. In this study, we investigated the oncogenic potential of IGF-2 in IGF2-overexpressing CRC models and the efficacy of MEDI-573, an IGF-1/2-neutralizing antibody. We found that a subset of CRC cell lines express high IGF-2 levels owing to an increased DNA copy number and hypermethylation in the H19 promoter of the IGF2 gene. MEDI-573 efficiently neutralized IGF-2 and induced apoptosis, which resulted in significant tumor growth inhibition in CRC mouse models that express high levels of IGF-2. These effects were specific to CRCs overexpressing IGF-2, as MEDI-573 did not affect the growth CRC cell lines with normal levels. Moreover, blockade of IGF-2 by MEDI-573 modulated other signaling pathways, suggesting combination therapies with inhibitors of these pathways. Indeed, in vivo efficacy was significantly enhanced when MEDI-573 was used in combination with trastuzumab, AZD2014 (dual mTORC1/2i), AZD5363 (AKTi) and selumetinib (AZD6244/ARRY-142886, MEK1/2i) or cetuximab. These results demonstrate that overexpressed IGF-2 is the major tumorigenic driver in a subset of CRCs and encourage testing of MEDI-573, alone and in combinations, in IGF2-overexpressing CRC patients. PMID- 27399334 TI - A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. AB - Epithelial-mesenchymal transition (EMT) is a critical event in metastasis of colorectal cancer (CRC). Rho/ROCKs signaling has a pivotal role in orchestrating actin cytoskeleton, leading to EMT and cancer invasion. However, the underlying mechanisms for ROCKs activation are not fully understood. Here, we identified FOXM1D, a novel isoform of Forkhead box M1 (FOXM1) that has a pivotal role in ROCKs activation by directly interacting with coiled-coil region of ROCK2. FOXM1D overexpression significantly polymerizes actin assembly and impairs E-cadherin expression, resulting in EMT and metastasis in xenograft mouse model and knockdown of FOXM1D has the opposite effect. Moreover, a high FOXM1D level correlates closely with clinical CRC metastasis. FOXM1D-induced ROCKs activation could be abrogated by the ROCKs inhibitors Y-27632 and fasudil. These observations indicate that the FOXM1D-ROCK2 interaction is crucial for Rho/ROCKs signaling and provide novel insight into actin cytoskeleton regulation and therapeutic potential for CRC metastasis. PMID- 27399335 TI - FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation. AB - Colorectal cancer (CRC), the second leading cause of cancer-related deaths in the US, has been treated with targeted therapies. However, the mechanisms of differential responses and resistance of CRCs to targeted therapies are not well understood. In this study, we found that genetic alterations of FBW7, an E3 ubiquitin ligase and a tumor suppressor frequently mutated in CRCs, contribute to resistance to targeted therapies. CRC cells containing FBW7-inactivating mutations are insensitive to clinically used multi-kinase inhibitors of RAS/RAF/MEK/ERK signaling, including regorafenib and sorafenib. In contrast, sensitivity to these agents is not affected by oncogenic mutations in KRAS, BRAF, PIK3CA or p53. These cells are defective in apoptosis owing to blocked degradation of Mcl-1, a pro-survival Bcl-2 family protein. Deleting FBW7 in FBW7 wild-type CRC cells abolishes Mcl-1 degradation and recapitulates the in vitro and in vivo drug-resistance phenotypes of FBW7-mutant cells. CRC cells selected for regorafenib resistance have progressive enrichment of pre-existing FBW7 hotspot mutations, and are cross-resistant to other targeted drugs that induce Mcl-1 degradation. Furthermore, a selective Mcl-1 inhibitor restores regorafenib sensitivity in CRC cells with intrinsic or acquired resistance. Together, our results demonstrate FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. PMID- 27399337 TI - Regulation of microRNA expression by HMGA1 proteins. PMID- 27399338 TI - Quantifying Dimer and Trimer Formation of Tri-n-butyl Phosphates in Different Alkane Diluents: FTIR Study. AB - Tri-n-butyl phosphate (TBP), a representative of neutral organophosphorous metal ion-extracting reagents, is an important ligand used in solvent extraction processes for the recovery of uranium and plutonium from spent nuclear fuel, as well as other non-nuclear applications. Ligand-ligand and organic solvent-ligand interactions play an important role in these processes. The self-association behavior of TBP in various alkane diluents of different chain lengths (8, 12, and 16 carbons) and a branched alkane (iso-octane) was investigated by Fourier transform infrared spectroscopic measurements. By careful deconvolution of the spectra into multiple peaks, our results indicate that TBP self-associates to form not only dimers, as previous studies showed, but also trimers in the practical concentration range. Using a mathematical fitting procedure, the dimerization and trimerization constants were determined. As expected, these equilibrium constants are dependent on the solvent used. As the alkane chain for linear hydrocarbon solvents becomes longer, dimerization decreases whereas trimerization increases. For the more branched hydrocarbon, we observe a significantly higher dimerization constant. These effects are most likely due to the intermolecular van der Waals interactions between the butyl tails of each TBP molecule and the diluent hydrocarbon chain as all solvents in this study are relatively nonpolar. PMID- 27399336 TI - MUC13 protects colorectal cancer cells from death by activating the NF-kappaB pathway and is a potential therapeutic target. AB - MUC13 is a transmembrane mucin glycoprotein that is over produced by many cancers, although its functions are not fully understood. Nuclear factor-kappaB (NF-kappaB) is a key transcription factor promoting cancer cell survival, but therapeutically targeting this pathway has proved difficult because NF-kappaB has pleiotropic functions. Here, we report that MUC13 prevents colorectal cancer cell death by promoting two distinct pathways of NF-kB activation, consequently upregulating BCL-XL. MUC13 promoted tumor necrosis factor (TNF)-induced NF-kappaB activation by interacting with TNFR1 and the E3 ligase, cIAP1, to increase ubiquitination of RIPK1. MUC13 also promoted genotoxin-induced NF-kappaB activation by increasing phosphorylation of ATM and SUMOylation of NF-kappaB essential modulator. Moreover, elevated expression of cytoplasmic MUC13 and NF kappaB correlated with colorectal cancer progression and metastases. Our demonstration that MUC13 enhances NF-kappaB signaling in response to both TNF and DNA-damaging agents provides a new molecular target for specific inhibition of NF kappaB activation. As proof of principle, silencing MUC13 sensitized colorectal cancer cells to killing by cytotoxic drugs and inflammatory signals and abolished chemotherapy-induced enrichment of CD133+ CD44+ cancer stem cells, slowed xenograft growth in mice, and synergized with 5-fluourouracil to induce tumor regression. Therefore, these data indicate that combining chemotherapy and MUC13 antagonism could improve the treatment of metastatic cancers. PMID- 27399339 TI - Solid Phase Synthesis of (Benzannelated) Six-Membered Heterocycles via Cyclative Cleavage of Resin-Bound Pseudo-Oxazolones. AB - A solid supported procedure for the synthesis of benzoxazinones, dihydropyrazinones, quinoxalinones, and dihydrooxazinones using immobilized oxazolones in combination with difunctional nucleophiles as cleavage agent is presented. The scope of the novel method has been demonstrated through subsequent modification of the parent oxazolone scaffold on solid supports using conversions with electrophiles or CuAAC reactions to give functionalized pyrazin-2-ones. The described method allows the synthesis of the target heterocycles in good yields via three to five steps on solid phases with only one chromatographic purification step. PMID- 27399340 TI - Anti-neuroinflammatory constituents from the fungus Penicillium purpurogenum MHZ 111. AB - A new dihydroisocoumarin (1) and a new coumarin (2), along with eight known metabolites (3-10), were isolated from the solid substrate fermentation cultures of the fungus Penicillium purpurogenum MHZ 111. Their structures were elucidated by extensive spectroscopic analysis and comparison of their spectroscopic and physicochemical data with the literature values. Compounds 2 and 8 showed inhibition of nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 26.5 and 52.7 MUM, respectively. PMID- 27399342 TI - Influence of herbal combinations on the extraction efficiencies of chemical compounds from Cinnamomum cassia, Paeonia lactiflora, and Glycyrrhiza uralensis, the herbal components of Gyeji-tang, evaluated by HPLC method. AB - During decoction process, the ingredients of herbal formula interact with each other, such that therapeutic properties and chemical extraction characteristics are altered. The crude drugs, Cinnamomum cassia (CC), Paeonia lactiflora (PL), and Glycyrrhiza uralensis (GU), are the main herbal constituents of Gyeji-tang, a traditional herbal formula. To evaluate the chemical interaction between CC, PL, and GU during the course of decoction, quantification of 16 marker compounds in the herbal decoction, performed using a Box-Behnken experimental design, was carried out by HPLC-diode array detection using validated method. Correlations between the amounts of marker compounds from CC, PL, and GU were assessed by multiple regression analysis. The results obtained showed that amounts of single herb marker compounds significantly changed (usually decreased) by decoction in the presence of other herbs and that these changes depended on the chemical natures of the markers and the herbal medicines present. Results also demonstrated that the extraction efficiencies of marker compounds increased when the proportion of the herb containing them was increased and decreased in proportion to amounts of herbs added. In conclusion, chemical interactions between compositional herbal medicines may occur when herbs are co-decocted. This study provides insight of understanding the herbal interactions in herbal formulae. PMID- 27399341 TI - Plastid-nucleus communication involves calcium-modulated MAPK signalling. AB - Chloroplast retrograde signals play important roles in coordinating the plastid and nuclear gene expression and are critical for proper chloroplast biogenesis and for maintaining optimal chloroplast functions in response to environmental changes in plants. Until now, the signals and the mechanisms for retrograde signalling remain poorly understood. Here we identify factors that allow the nucleus to perceive stress conditions in the chloroplast and to respond accordingly by inducing or repressing specific nuclear genes encoding plastid proteins. We show that ABI4, which is known to repress the LHCB genes during retrograde signalling, is activated through phosphorylation by the MAP kinases MPK3/MPK6 and the activity of these kinases is regulated through 14-3-3omega mediated Ca(2+)-dependent scaffolding depending on the chloroplast calcium sensor protein CAS. These findings uncover an additional mechanism in which chloroplast modulated Ca(2+) signalling controls the MAPK pathway for the activation of critical components of the retrograde signalling chain. PMID- 27399343 TI - Metabolic profile of 5-hydroxy-4-methoxycanthin-6-one, a typical canthinone alkaloid, in rats determined by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques. AB - Picrasma quassioides (D. Don) Benn. is a traditional Chinese medicine used clinically to treat gastrointestinal disorders and as a vermifuge. 5-Hydroxy-4 methoxycanthin-6-one (CAN), a major canthinone alkaloid found in P. quassioides, has significant pharmacological activities. In the present study, a method using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques, including extracted ion chromatogram, multiple mass defect filter, precursor/product ion scanning and neutral loss scanning was developed to screen and characterize the phase I and II metabolites of CAN in plasma, bile, urine and feces of rats after a single oral dose of 20mg/kg. A total of 17 metabolites were tentatively or conclusively identified. Pathways for the metabolism of CAN have been proposed, and include hydroxylation, N-decarbonylation, methylation, oxidation and sequential conjugation. A previously unknown metabolically active site at the C4-C6 position and a novel N decarbonylation-oxidation metabolic pathway for the prototypical canthinone alkaloid, CAN, were discovered. Our results provide valuable information about the in vivo metabolism of CAN that can also be used as a comprehensive guide for the biotransformation of other canthinone alkaloids. PMID- 27399344 TI - Serum metabonomics study of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced acute hepatotoxicity in rats by (1)H NMR analysis. AB - Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the exact hepatoprotective mechanism of CS was still looking forward to further elucidation by far. In present work, metabonomic study of biochemical changes in the serum of carbon tetrachloride (CCl4)-induced acute liver injury rats after CS treatment were performed using proton nuclear magnetic resonance ((1)H-NMR) analysis. Metabolic profiling by means of principal components analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced by CS treatment. A total of 9 metabolites including isoleucine (1), lactate (2), alanine (3), glutamine (4), acetone (5), succinate (6), phosphocholine (7), d-glucose (8) and glycerol (9) were considered as potential biomarkers involved in the development of CCl4-induced acute liver injury. According to pathway analysis by metabolites identified and correlation network construction by Pearson's correlation coefficency matrix, alanine, aspartate and glutamate metabolism and glycerolipid metabolism were recognized as the most influenced metabolic pathways associated with CCl4 injury. As a result, notably, deviations of metabolites 1, 3, 4, 7 and 9 in the process of CCl4-induced acute liver injury were improved by CS treatment, which suggested that CS mediated synergistically abnormalities of the metabolic pathways, composed of alanine, aspartate and glutamate metabolism and glycerolipid metabolism. In this study, it was the first report to investigate the hepatoprotective effect of the CS based on metabonomics strategy, which may be a potentially powerful tool to interpret the action mechanism of traditional Chinese folk medicines. PMID- 27399345 TI - Discrimination of Proteins Using an Array of Surfactant-Stabilized Gold Nanoparticles. AB - Protein analysis is a fundamental aspect of biochemical research. Gold nanoparticles are an emerging platform for various biological applications given their high surface area, biocompatibility, and unique optical properties. The colorimetric properties of gold nanoparticles make them ideal for point-of-care diagnostics. Different aspects of gold nanoparticle-protein interactions have been investigated to predict the effect of protein adsorption on colloidal stability, but the role of surfactants is often overlooked, despite their potential to alter both protein and nanoparticle properties. Herein we present a method by which gold nanoparticles can be prepared in various surfactants and used for array-based quantification and identification of proteins. The exchange of surfactant not only changed the zeta potential of those gold nanoparticles but also drastically altered their aggregation response to five different proteins (bovine serum albumin, human serum albumin, immunoglobulin G, lysozyme, and hemoglobin) in a concentration-dependent manner. Finally, we demonstrate that varying surfactant concentration can be used to control assay sensitivity. PMID- 27399346 TI - Gendered role of appraisals of safety in psychological outcome in relation to trauma. AB - OBJECTIVE: This study investigated gender differences in the role of appraisals of safety in the relationship between exposure to violence and trauma-related symptoms among South African adolescents living in low socioeconomic settings. Limited research exists in developing contexts on the role of cognitive appraisals in mitigating outcome following exposure to violence. Given the prevalence of violence in South Africa and the vulnerability of youth, this type of research is valuable in identifying adolescents at risk of negative psychological outcome following exposure, and in informing intervention efforts. METHOD: Adolescents (N = 498) completed an adapted version of the Harvard Trauma Questionnaire (Mollica et al., 1992) and the Safety Index (Ward, Flisher, Zissis, Muller, & Lombard, 2001). RESULTS: The results indicate a significant positive relationship between all violence subscales and trauma-related symptoms, whereas a significant negative relationship was found between sense of safety and trauma related symptoms. Important gender differences were identified in the role of appraisals of safety, with more effects noted for women than men. For men, the obtained results only demonstrated a health-sustaining role. For women, the results indicated a health-sustaining role, an indirect effect, and a stress reducing role. CONCLUSION: These findings stress the necessity of gender-specific interventions. Assessment of psychological trauma, particularly among female adolescents, needs to include measures of cognitive appraisals related to safety. Therapeutic techniques that may be particularly beneficial to adolescent girls are those focusing on promoting sense of safety and targeting dysfunctional threat appraisals. (PsycINFO Database Record PMID- 27399347 TI - N-Terminal Prosomatostatin as a Risk Marker for Cardiovascular Disease and Diabetes in a General Population. AB - CONTEXT: Somatostatin inhibits a range of hormones, including GH, insulin, and glucagon, but little is known about its role in the development of cardiometabolic disease. OBJECTIVE: The objective of the study was to investigate whether fasting plasma concentration of N-terminal prosomatostatin (NT-proSST) is associated with the development of diabetes, coronary artery disease (CAD), and mortality. DESIGN, SETTING, AND PARTICIPANTS: NT-proSST was measured in plasma from 5389 fasting participants of the population-based study Malmo Preventive Project, with a mean baseline age of 69.4 +/- 6.2 years. Cox proportional hazards models adjusted for traditional cardiovascular risk factors were used to investigate the relationships between baseline NT-proSST and end points, with a mean follow-up of 5.6 +/- 1.4 years. MAIN OUTCOME MEASURES: CAD, diabetes, and mortality were measured. RESULTS: Overall, NT-proSST (hazard ratio [HR] per SD increment of log transformed NT-proSST) was unrelated to the risk of incident diabetes (220 events; HR 1.05; 95% confidence interval [CI] 0.91-1.20; P = .531) but was related to the risk of incident CAD (370 events; HR 1.17; 95% CI 1.06 1.30; P = .003), all-cause mortality (756 events; HR 1.24; 95% CI 1.15-1.33; P < .001), and cardiovascular mortality (283 events; HR 1.33; 95% CI 1.19-1.43; P < .001). The relationships were not linear, with most of the excess risk observed in subjects with high values of NT-proSST. Subjects in the top vs bottom decile had a severely increased risk of incident CAD (HR 2.41; 95% CI 1.45-4.01; P < .001), all-cause mortality (HR 1.84; 95% CI 1.33-2.53; P < .001), and cardiovascular mortality (HR 2.44; 95% CI 1.39-4.27; P < .001). CONCLUSION: NT proSST was significantly and independently associated with the development of CAD, all-cause mortality, and cardiovascular mortality. PMID- 27399348 TI - Defining the Newborn Blood Spot Screening Reference Interval for TSH: Impact of Ethnicity. AB - CONTEXT: There is variability in the congenital hypothyroidism (CH) newborn screening TSH cutoff across the United Kingdom. OBJECTIVE: To determine the influences of year, gender, and ethnicity on screening variability and examine whether there is an optimal operational TSH cutoff. DESIGN AND SETTING: Single center, retrospective population study using blood spot TSH cards received by the Great Ormond Street Hospital Screening Laboratory between 2006 and 2012. PATIENTS: A total of 824 588 newborn screening blood spot TSH cards. INTERVENTION: Blood spot TSH results were recorded with demographic data including the Ethnic Category Code. MAIN OUTCOME MEASURES: The proportions of samples exceeding different TSH cutoffs, ranked by ethnicity. RESULTS: The proportion of samples exceeding the TSH cutoff increased over time, with the cutoff at 4 mU/L, but not at 6 mU/L. There was a consistent trend with ethnicity, irrespective of cutoff, with the odds ratio of exceeding the TSH cutoff lowest (~1.0) in White babies, higher in Pakistani and Bangladeshi (>2.0), and highest in Chinese (>3.5). CONCLUSIONS: The blood spot TSH screening data demonstrate a clear ranking according to ethnicity for differences in mean TSH. This suggests that there may be ethnic differences in thyroid physiology. Ethnic diversity within populations needs to be considered when establishing and interpreting screening TSH cutoffs. PMID- 27399349 TI - Impaired Follistatin Secretion in Cirrhosis. AB - CONTEXT: Follistatin is a liver-derived inhibitor of the muscle-growth inhibitor myostatin. Reduction in acute follistatin release may help explain muscle loss in liver cirrhosis. OBJECTIVE: The study aimed to investigate the capacity of acute follistatin release in patients with liver cirrhosis compared to healthy control participants. DESIGN, SETTING, AND PARTICIPANTS: To experimentally increase the glucagon-insulin ratio (mimicking the hormonal effect of exercise), we infused glucagon/somatostatin (to inhibit insulin secretion) and compared the acute follistatin increase in eight male cirrhosis patients with eight healthy control participants. Patients and controls received 1-hour glucagon/somatostatin and saline infusions on 2 separate days. MAIN OUTCOME MEASURE: Follistatin was measured during and 5 hours after termination of infusions. RESULTS: The peak follistatin change was significantly decreased in patients with liver cirrhosis compared to healthy control participants (1.9 (interquartile range, 1.4-2.5) versus 3.6 (interquartile range, 3.0-4.0), respectively; P = .003). Patients with liver cirrhosis demonstrated significantly decreased amounts of appendicular lean mass compared to healthy controls (27.6 +/- 3.8 vs 34.5 +/- 2.9%, respectively; P = .001). CONCLUSIONS: Patients with cirrhosis show impaired capacity to acutely secrete follistatin. The decrease in acute follistatin release may contribute to the loss of muscle mass in liver cirrhosis. PMID- 27399350 TI - Arginase Inhibition Improves Microvascular Endothelial Function in Patients With Type 2 Diabetes Mellitus. AB - OBJECTIVES: The development of microvascular complications in diabetes is a complex process in which endothelial dysfunction is important. Emerging evidence suggests that arginase is a key mediator of endothelial dysfunction in type 2 diabetes mellitus by reciprocally regulating nitric oxide bioavailability. The aim of this prospective intervention study was to test the hypothesis that arginase activity is increased and that arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. DESIGN: Microvascular endothelium-dependent and independent dilatation was determined in patients with type 2 diabetes (n = 12) and healthy age-matched control subjects (n = 12) with laser Doppler flowmetry during iontophoretic application of acetylcholine and sodium nitroprusside, respectively, before and after administration of the arginase inhibitor Nomega hydroxy-nor-L-arginine (120 min). Plasma ratios of amino acids involved in arginase and nitric oxide synthase activities were determined. The laser Doppler flowmetry data were the primary outcome variable. RESULTS: Microvascular endothelium-dependent dilatation was impaired in subjects with type 2 diabetes (P < .05). After administration of Nomega-hydroxy-nor-L-arginine, microvascular endothelial function improved significantly in patients with type 2 diabetes to the level observed in healthy controls. Endothelium-independent vasodilatation did not change significantly. Subjects with type 2 diabetes had higher levels of ornithine and higher ratios of ornithine/citrulline and ornithine/arginine (P < .05), suggesting increased arginase activity. CONCLUSION: Arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. Arginase inhibition may represent a novel therapeutic strategy to improve microvascular endothelial function in patients with type 2 diabetes. PMID- 27399351 TI - Endothelial Dysfunction as a Link Between Cardiovascular Risk Factors and Peripheral Neuropathy in Diabetes. AB - CONTEXT: Cardiovascular risk factors are well-known predictors of the development of diabetic peripheral neuropathy (DPN), which has traditionally been considered as a manifestation of diabetes-associated microangiopathy. Because endothelial dysfunction is strongly associated with all cardiovascular risk factors, we hypothesized that it may be a link between cardiovascular risk factors and DPN. OBJECTIVE: The primary objective of this study was to test whether endothelial dysfunction is a predictor of DPN. DESIGN AND SETTING: This is a cross-sectional analysis of a cohort composed of patients followed at the Microcirculatory Laboratory, Beth Israel Deaconess Medical Center. PATIENTS: Participants with diabetes without DPN (n = 192) and with DPN (n = 166), subjects with prediabetes (n = 75), and nondiabetic controls (n = 59) were included. INTERVENTIONS: Endothelial function was assessed with flow-mediated dilation (FMD) of the brachial artery. Inflammatory cytokines and biomarkers of endothelial function (soluble intercellular and vascular cell adhesion molecules) were quantified using a multiplex bead-based immunoassay. Neurological assessment included the neuropathy disability score (NDS). MAIN OUTCOME MEASURE: The relationship between FMD and NDS assessed using multiple linear regression. RESULTS: In addition to already known risk factors of DPN, FMD was strongly associated with NDS (beta = 0.24; P < .001). Sensitivity analysis that removed FMD from the model provided similar results for soluble intercellular cell adhesion molecule-1, another biomarker of endothelial function. Confirmatory factor analysis further showed that endothelial dysfunction is a significant mediator between glycosylated hemoglobin and diabetes duration and diabetic complications. CONCLUSIONS: This study shows that endothelial dysfunction occurs early in the pathophysiology of diabetes and is a link between cardiovascular risk factors and DPN. PMID- 27399352 TI - Vitamin D-Dependent Rickets Type 1 Caused by Mutations in CYP27B1 Affecting Protein Interactions With Adrenodoxin. AB - CONTEXT: CYP27B1 converts 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3, playing a vital role in calcium homeostasis and bone growth. Vitamin D dependent rickets type 1 (VDDR-1) is a rare autosomal recessive disorder caused by mutations in CYP27B1. OBJECTIVE: The objective of the study was an enzymatic and structural analysis of mutations in a patient with calcipenic rickets. Design, Setting, Patient, and Intervention: Two siblings presented with calcipenic rickets and normal 1,25-dihydroxyvitamin D3 levels. CYP27B1 gene analysis showed compound heterozygous mutations confirming VDDR-1. We studied wild-type CYP27B1 and mutations H441Y and R459L by computational homology modeling, molecular dynamics simulations, and functional studies using a luciferase assay. The patients were successfully treated with calcitriol. MAIN OUTCOME: The main outcomes of the study were novel mutations leading to a severe loss of CYP27B1 activities for metabolism of 25-hydroxyvitamin D3. RESULTS: Mitochondrial cytochrome P450s require adrenodoxin (FDX1) and adrenodoxin reductase. We created models of CYP27B1-FDX1 complex, which revealed negative effects of mutations H441Y and R459L. Upon structural analysis, near-identical folds, protein contact areas, and orientations of heme/iron-sulfur cluster suggested that both mutations may destabilize the CYP27B1-FDX1 complex by negating directional interactions with adrenodoxin. This system is highly sensitive to small local changes modulating the binding/dissociation of adrenodoxin, and electron-transporting efficiency might change with mutations at the surface. Functional assays confirmed this hypothesis and showed severe loss of activity of CYP27B1 by both mutations. CONCLUSIONS: This is the first report of mutations in CYP27B1 causing VDDR-1 by affecting protein-protein interactions with FDX1 that results in reduced CYP27B1 activities. Detailed characterization of mutations in CYP27B1 is required for understanding the novel molecular mechanisms causing VDDR-1. PMID- 27399354 TI - Perioperative blood transfusion in radical cystectomy: Analysis of the National Surgical Quality Improvement Program database. AB - OBJECTIVES: To determine whether perioperative blood transfusion is associated with worse 30-day postoperative outcomes in radical cystectomy patients. METHODS: Utilizing the National Surgical Quality Improvement Program database, we identified 2934 patients diagnosed with bladder cancer (International Classification of Diseases Ninth Revision codes 188-188.9) who underwent radical cystectomy (Current Procedure Terminology codes 51570, 51575, 51580, 51585, 51590, 51595, 51596) between 2005 and 2013. Patients were stratified by transfusion status and assessed based on four composite postoperative outcomes: morbidity, surgical site infection, mortality and readmission. Multivariate regression models were used to determine significant independent predictors of the composite outcomes. RESULTS: Overall, 40.1% of patients received a transfusion, and there were significant differences in baseline variables such as age, sex, body mass index, smoking history and comorbidities. Transfusion was associated with increased morbidity, surgical site infection, readmission, operative time and length of stay on unadjusted analyses. On multivariate regression, transfusion was associated with increased morbidity (OR 1.361, 95% CI 1.131-1.638) and surgical site infection (OR 1.371, 95% CI 1.070-1.757). CONCLUSIONS: Perioperative blood transfusion is associated with increased risk of postoperative infection and morbidity. Previous work in this area has focused on negative long-term oncological outcomes, but this is the first study to examine short-term postoperative outcomes. Future research should focus on the immunosuppressive mechanism of perioperative blood transfusion and on restrictive transfusion guidelines for oncology patients. PMID- 27399353 TI - Cholesterol Efflux Capacity and Subclasses of HDL Particles in Healthy Women Transitioning Through Menopause. AB - CONTEXT: Growing evidence challenges the concept that high-density lipoprotein cholesterol (HDL-C) is cardioprotective after menopause. HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) might be better predictors of cardiovascular risk. OBJECTIVE: Quantify alterations in HDL-P and CEC during menopause, correlating those changes with alterations in estradiol (E2) and FSH. DESIGN: Longitudinal study of HDL metrics before and after menopause as indexed by the final menstrual period (FMP). PARTICIPANTS: Forty-six women, mean baseline age 47.1 years, 33% black, 67% white. MAIN OUTCOMES AND MEASURES: HDL-P concentration (HDL-PIMA) by calibrated ion mobility analysis (IMA); macrophage CEC with cAMP-stimulated macrophages; ATP-binding cassette transporter A1 (ABCA1)-specific CEC with BHK cells expressing human ABCA1. RESULTS: After a median of 2.1 years since FMP, both HDL-C (P = .03) and HDL-PIMA (P = .01) increased, with a selective increase in large HDL-PIMA (P = .01), whereas sizes of medium and small HDL-PIMA were decreased (P < .05). These changes were independent of race, body mass index, and time difference. Macrophage CEC and ABCA1-specific CEC increased after FMP (both P < .001). Greater declines in E2 correlated with larger increases in small HDL-PIMA (P = .01), whereas greater increases in FSH associated with greater reductions in the size of medium HDL-PIMA (P = .04). Macrophage CEC and ABCA1-specific CEC correlated positively with E2 levels only before menopause (P = .04 and .009, respectively). CONCLUSIONS: Large HDL-PIMA and CEC increased significantly in the early phase of the menopausal transition. Whether patterns of these alterations differ in late postmenopause is unknown. Further exploration is needed to assess that and to determine whether the reported changes in HDL metrics associate with increased cardiovascular risk after menopause. PMID- 27399355 TI - Clinician-Reported Barriers to Implementing Breast Cancer Chemoprevention in the UK: A Qualitative Investigation. AB - AIMS: The use of tamoxifen and raloxifene as preventive therapy for women at increased risk of breast cancer was approved by the National Institute for Health and Care Excellence (NICE) in 2013. We undertook a qualitative investigation to investigate the factors affecting the implementation of preventive therapy within the UK. METHODS: We recruited general practitioners (GPs) (n = 10) and clinicians working in family history or clinical genetics settings (FHCG clinicians) (n = 15) to participate in semi-structured interviews. Data were coded thematically within the Consolidated Framework for Implementation Research. RESULTS: FHCG clinicians focussed on the perceived lack of benefit of preventive therapy and difficulties interpreting the NICE guidelines. FHCG clinicians felt poorly informed about preventive therapy, and this discouraged patient discussions on the topic. GPs were unfamiliar with the concept of preventive therapy, and were not aware that they may be asked to prescribe it for high-risk women. GPs were reluctant to initiate therapy because it is not licensed, but were willing to continue a prescription if it had been started in secondary or tertiary care. CONCLUSIONS: Barriers to implementing preventive therapy within routine clinical practice are common and could be addressed by engaging all stakeholders during the development of policy documents. PMID- 27399356 TI - Deep Brain Stimulation of the Fornix: Engaging Therapeutic Circuits and Networks in Alzheimer Disease. PMID- 27399357 TI - Deep Brain Stimulation Targets, Technology, and Trials: Two Decades of Progress. AB - ABBREVIATIONS: AD, Alzheimer diseaseDBS, Deep brain stimulationFDA, Food and Drug AdministrationMER, Microelectrode recording. PMID- 27399358 TI - Laser Ablation vs Open Resection for Deep-Seated Tumors: The Case for Open Resection. PMID- 27399359 TI - Laser Ablation vs Open Resection for Deep-Seated Tumors: Evidence for Laser Ablation. PMID- 27399360 TI - Mentorship: Service, Education, Progress: An Interview With the Congress of Neurological Surgeons President Dr Nathan R. Selden. PMID- 27399361 TI - Minimally Invasive Spine Surgery and Sagittal Correction. PMID- 27399363 TI - Minimally Invasive Spinal Deformity Surgery: Current State and Future Direction. PMID- 27399364 TI - Trigeminal Neuralgia: New Evidence for Origins and Surgical Treatment. PMID- 27399362 TI - Molecular, Cellular, and Genetic Determinants of Sporadic Brain Arteriovenous Malformations. PMID- 27399365 TI - History and Current Status of Neurosurgery in Turkey. PMID- 27399366 TI - Neuroendovascular Surgery for Acute Ischemic Stroke: All Patients All the Time. PMID- 27399367 TI - First Treatment in Infants With Hydrocephalus: The Case for Shunt. PMID- 27399369 TI - Japanese Congress of Neurological Surgeons Presidential Address. PMID- 27399370 TI - Advances in Immunotherapy: Abhijit Guha Award Presentation. PMID- 27399368 TI - First Treatment in Infants With Hydrocephalus: The Case for Endoscopic Third Ventriculostomy/Choroid Plexus Cauterization. PMID- 27399371 TI - Neurosurgical Education: A New Paradigm for Curriculum, Core, and Subspecialty Training. PMID- 27399372 TI - The Barrow Randomized Operating Room Traffic (BRITE) Trial: An Observational Study on the Effect of Operating Room Traffic on Infection Rates. PMID- 27399373 TI - The Profile of a Smoker and Its Impact on Outcomes After Cervical Spine Surgery. PMID- 27399374 TI - Mechanisms of Injury as a Diagnostic Predictor of Sport-Related Concussion Severity in Football, Basketball, and Soccer: Results From a Regional Concussion Registry. PMID- 27399376 TI - The Dorsal Root Ganglion in the Pathogenesis of Chronic Neuropathic Pain. PMID- 27399375 TI - Odontoid Fractures and the Silver Tsunami: Evidence and Practice in the Very Elderly. PMID- 27399377 TI - Diffusion Weighted Magnetic Resonance Imaging Radiophenotypes and Associated Molecular Pathways in Glioblastoma. PMID- 27399378 TI - Relationship of Cerebral Arteriovenous Malformation Hemodynamics to Clinical Presentation, Angioarchitectural Features, and Hemorrhage. PMID- 27399584 TI - Survival and Reduction of Shiga Toxin-Producing Escherichia coli in a Fresh Cold Pressed Juice Treated with Antimicrobial Plant Extracts. AB - This study was conducted to evaluate the survival of 7 Shiga-toxigenic Escherichia coli (STEC) in fresh cold-pressed juice and the antimicrobial efficacy of 4 essential oils (EO: achillea, rosemary, sage, and thyme). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of each EO was determined using microdilution assays evaluated at pH levels 4 and 7; as well as at 4 and 25 degrees C; daily for up to 5 d. Results indicated that 5 of 7 serotypes survived well in cold-pressed raw juice for at least 4 d at 4 degrees C and pH 3.5 with no significant (P > 0.05) reduction in viability. The EO showed varying degrees of antimicrobial activity against the 7 STEC. The MIC and MBCs were lowest for thyme (2 MUg/L) and highest for sage (15 to 25 MUg/L). The antimicrobial activity was enhanced at low pH and temperature. Data showed that although the top 7 STEC could survive low pH and temperature in vitro and in cold-pressed juices, EO, especially from thyme and rosemary, reduced STEC to an undetectable level at 4 degrees C, suggesting that they could be used as natural antimicrobials in juice. PMID- 27399586 TI - [Psychiatric Rehabilitation - From the Linear Continuum Approach Towards Supported Inclusion]. AB - Background: For many decades, psychiatric rehabilitation in the German-speaking countries is following a conventional linear continuum approach. Methods: Recent developments in important fields related to psychiatric rehabilitation (UN Convention on the Rights of People with Disabilities, theory of rehabilitation, empirical research) are reviewed. Results: Common to all developments in the reviewed fields are the principles of choice, autonomy and social inclusion. These principles contradict the conventional linear continuum approach. Conclusions: The linear continuum approach of psychiatric rehabilitation should be replaced by the "supported inclusion"-approach. PMID- 27399587 TI - [Cooperation, Job Satisfaction and Burn Out - Sustainability in Outpatient Mental Health Care among Medical Specialists in Germany]. AB - Objective Cooperation, job satisfaction, and burn out risk are indicators of sustainability in mental health services. Thus they were assessed among registered medical specialists in outpatient mental health care in Germany. Method A postal survey consisting of three questionnaires about cooperation, job satisfaction, and burnout was carried out among all registered medical specialists in outpatient mental health care in Germany (n = 4,430). Results 14.1 % (n = 626) of the specialists responded to the survey. Quality and quantity of cooperation regarding mental health care services were rated diverse, job satisfaction was assessed medium to high, and burnout risk was low to medium. Higher job satisfaction correlated with good quality of cooperation, fewer years of practice, fewer patients' chronically ill, more patients who as well seek psychotherapy, and less time spent on cooperation. Low burn out risk correlated with good quality of cooperation, higher age, single practice setting and a higher amount of patients who as well seek psychotherapy. Conclusion Quality and quantity of cooperation in outpatient mental health care - especially regarding community mental health care institutions - should be fostered. Aspects to be considered to reinforce job satisfaction and minimize burn out risk are age, years of practice, quality and quantity of cooperation, practice setting, and the mixture of patients. PMID- 27399585 TI - Clinical presentation and risk factors of serious infections in children with Down syndrome treated for acute lymphoblastic leukemia. AB - BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) in children with Down syndrome (DS) is associated with a higher incidence of life-threatening infections compared to the overall pediatric population. The objective of this study was to describe infections and identify risk factors of microbiologically documented infections at a sterile site in children with DS during chemotherapy for ALL. PROCEDURE: We conducted a single-institution retrospective review of infectious episodes encountered by patients with DS during primary treatment for ALL. Correlations between features of clinical presentation and severity of microbiologically proven infections were investigated. RESULTS: Among 237 suspected infectious episodes encountered by 35 patients with DS and ALL (DS ALL), a total of 40 episodes (16.9%) had the clinical presentation of a severe infection (SI). Seventeen patients had 33 (13.9%) microbiologically proven infections from a sterile site. Fever was not part of the clinical presentation in 27% of microbiologically documented infectious episodes. The odds ratio of a microbiologically proven infection at a sterile site was significantly increased during a 7-day interval after treatment with glucocorticoids (2.18; 95% CI: 1.02 4.66; P = 0.04). Neither administration of anthracyclines in the preceding 14 days nor neutropenia correlated with infections. CONCLUSIONS: Serious infections in DS-ALL may present without typical signs such as fever. The immediate time period following administration of glucocorticoids is particularly associated with the risk of SIs. PMID- 27399588 TI - [Influence and Change of Self-Directedness in Dialectical Behavior Therapy]. AB - Objective Investigate influence and change of self-directedness (SD) in Dialectical-Behavior Therapy (DBT) for 26 female outpatients with borderline personality disorder (BPS). Method Variance analyses are used to evaluate psychopathology and interpersonal problems in 2 subgroups (low vs. high SD) with questionnaires at 3 measuring times over the period of 1 year. Results Low SD was associated with higher psychopathology, more interpersonal problems and lower symptomreduction. Over time of intervention the SD of all patients improved significantly. Conclusion DBT strengthens the SD of patients with BPD. A screening of SD before intervention, and systematic support should be considered. PMID- 27399589 TI - [Comparison of Aggressive Behavior, Compulsory Medication and Absconding Behavior Between Open and Closed door Policy in an Acute Psychiatric Ward]. AB - Objective According to legal requirements coercive treatment must be limited to acts necessary for the protection of patients and cannot be used for institutional interests. Here, we aimed to test the hypothesis that opening psychiatric wards can reduce the number of aggressive assaults and of coercive treatment without increasing absconding rates. Methods Numbers of absconding, coercive medication, fixation and special security actions were collected retrospectively and compared between phases of closed (N total = 409; N legally committed = 64) and 90 % of daytime opened (N total = 571; N legally committed = 99) doors in an acute psychiatric ward. Results During the phase of opened doors we observed significantly reduced aggressive assaults (p < 0,001) and coercive medication (p = 0,006) compared to the closed setting, while the absconding rate did not change (p = 0,20). Limitation Given the retrospective non-experimental design, no causal interpretations can be drawn. Conclusion The results suggest that open door is associated with reduction of aggressive assaults and coercive medication without increasing absconding rates. This speaks for a stronger implementation of open door policies in acute wards in order to preserve human rights in psychiatry. To collect more robust evidence for this thesis, longer phases should be monitored and moderating variables such as atmosphere and social cohesion should be assessed. PMID- 27399590 TI - [What Determines Treatment Recommendations of Relatives: The Role of Expectations, Negative Consequences and Control Attributions for the Treatment of Patients with Psychosis]. AB - Objective Therapy recommendations of relatives of individuals with psychotic disorders. Method A total of n = 52 inpatient relatives were interviewed about their attitude towards psychotherapy and antipsychotics. Results Over 80 % of the relatives recommended psycho- and pharmacotherapy. Concerns reduced recommendations for pharmacotherapy, poor/lack of hope for improvement reduced recommendations for psychotherapy. Conclusion The relatives' therapy recommendations could be influenced by discussing their concerns and expectations of success. PMID- 27399591 TI - [12-Month Prevalence and Consequences of Current Experiences of Physical and Psychological Violence in a Sample of Patients who Entered First Time a Psychotherapeutic Outpatient Clinic]. AB - Objective To examine current experiences of violence and its relationship with psychological burden in a psychotherapeutic outpatient sample. Methods 1074 patients of a psychotherapeutic outpatient-clinic of a university hospital completed a written violence screening questionnaire. Results Current experienced physical and psychological violence was two times higher compared to general population. Patients who experienced current violence reported significantly more psychological burden. Conclusion Use of violence screening in daily routine of a psychotherapeutic outpatient-clinic seems to be a promising approach to detect violence experiences. PMID- 27399592 TI - [Disability Pension and Productivity Loss in Schizophrenia - An Empirical Analysis of the Financial Burden in Germany]. AB - Objective Quantification of the economic burden for society and the German Statutory Pension Insurance due to early retirement in schizophrenia. Methods Based on empirical data of the German Statutory Pension Insurance, productivity losses were calculated using the human capital approach. Results The total expenditures of the German Statutory Pension Insurance due to pension payments for schizophrenic insurants amounted to ? 450 million. Total indirect costs due to morbidity and mortality were estimated at ? 2,3 million. Average indirect costs per patient ranged between ? 17 000 - 28 000, depending on rates for discounting and inflation. Conclusion Regarding substantial economic consequences, preventive measures and therapeutic procedures should aim to prevent reduction in earning capacity and to promote occupational reintegration of schizophrenic patients. PMID- 27399593 TI - [Coercive Interventions in Psychiatry: Prevention and Patients' Preferences]. AB - Objective This study explores patients' preferences and measures of prevention of coercive methods in psychiatric treatment. Methods Structured interviews of 90 patients with psychotic disorders were undertaken, most of whom had previously experienced coercive methods. Results Participants saw preventive potential in a wider availability of individual non-pharmacological therapy, improvement of staff professional competence and communication skills, high staff-to-patient ratios and retreat facilities. The majority of participants preferred forced medication and manual restraint in case of self-endangerment, and forced medication and mechanical restraint in the event of endangerment of others. Conclusion Patients' suggestions relating to prevention of coercion are in line with most expert's opinions. In case coercive methods are required, manual restraint and application of forced medication is accepted as the treatment of choice according to most patients in case of self-endangerment. PMID- 27399594 TI - [Assessment of Aggressive Assaults by Patients from 2008 to 2015 in two German Psychiatric Hospitals: Results and Implications]. AB - Objective: Studies on the frequency and the overall trend in recent years of aggressive assaults by patients in German psychiatric hospitals are scarce. We investigated the frequency of physical aggression by patients between 2008 and 2015 in two hospitals for psychiatry and psychotherapy. Methods: Aggressive and violent events were routinely assessed (spontaneous reports) and were analyzed in a differentiated way. Results: The frequency of aggressive behavior of patients towards others showed a slightly, but significantly increase since 2008, although at a low level. This increase was almost entirely caused by an increase of aggressive assaults against nursing staff. Conclusions: The relative frequency of aggressive behavior by patients (4/1000 cases) was on average rather low. The increase of assaults particularly against nursing personnel gives nonetheless reason to scrutinize and continuously optimize measures for prevention and therapy of patients' aggressive behavior. PMID- 27399595 TI - [Costs of Mental Health Care in Patients with Posttraumatic Stress Disorder Related to Sexual Abuse One Year Before and After Inpatient DBT-PTSD]. AB - Objective In Germany, patients with posttraumatic stress disorder (PTSD) related to childhood sexual abuse (CSA) often receive inpatient treatment. However, data on utilization and costs of mental health care as well as on the impact of trauma focused treatment are missing. Methods Within the context of a randomized controlled trial mental health service utilization was assessed in female patients with PTSD related to CSA. Data on psychiatric-psychotherapeutic inpatient and outpatient treatment and psychotropic medication was obtained for the year before and after inpatient DBT-PTSD. Results The mean total costs of utilization of psychiatric-psychotherapeutic care and use of psychotropics were ? 18.100 per patient in the year before and ? 7.233 in the year after DBT-PTSD. The significant cost decrease was due to large reductions in inpatient treatment days (on average 57 days before and 14 days after DBT-PTSD), while outpatient treatment and psychotropic medication remained unchanged. Conclusion PTSD related to CSA is associated with high utilization and costs of mental health care. The results suggest that DBT-PTSD might contribute to reducing the mental health care costs. PMID- 27399596 TI - [Antidepressive Combination Treatment in Patients with Severe Depressive Episode: The Practice of Prescription in a Clinical Sample 2012]. AB - Objectives Polypharmacy in the treatment of severe psychiatric disorders may include promising treatment options, yet may also be subject to additional side effects and interactions. In patients with severe depression, the prevalence of antidepressive (AD) combination treatment has not been thoroughly assessed yet. Methods We assessed the prevalence of antidepressive combination treatment in a sample of hospital patients at the LVR-Clinic in Dusseldorf, Germany in 2012. Results 1.198 residential or semi-residential patients were diagnosed with severe depressive episode and were treated with at least one antidepressant. 25.1 % of those received a combination of at least two antidepressants. The most frequent combination approaches were tri- and tetracyclic AD with selective serotonin reuptake inhibitors (SSRI) yet various other combination approaches were observed. Conclusions Combination treatment is a common strategy. Future trends could be monitored via electronic prescription software, yet prospective confirmatory trials are needed to assess the rationale of different combination treatment approaches. PMID- 27399597 TI - Development of a Korean Fracture Risk Score (KFRS) for Predicting Osteoporotic Fracture Risk: Analysis of Data from the Korean National Health Insurance Service. AB - BACKGROUND: Asian-specific prediction models for estimating individual risk of osteoporotic fractures are rare. We developed a Korean fracture risk prediction model using clinical risk factors and assessed validity of the final model. METHODS: A total of 718,306 Korean men and women aged 50-90 years were followed for 7 years in a national system-based cohort study. In total, 50% of the subjects were assigned randomly to the development dataset and 50% were assigned to the validation dataset. Clinical risk factors for osteoporotic fracture were assessed at the biennial health check. Data on osteoporotic fractures during the follow-up period were identified by ICD-10 codes and the nationwide database of the National Health Insurance Service (NHIS). RESULTS: During the follow-up period, 19,840 osteoporotic fractures were reported (4,889 in men and 14,951 in women) in the development dataset. The assessment tool called the Korean Fracture Risk Score (KFRS) is comprised of a set of nine variables, including age, body mass index, recent fragility fracture, current smoking, high alcohol intake, lack of regular exercise, recent use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis. The KFRS predicted osteoporotic fractures over the 7 years. This score was validated using an independent dataset. A close relationship with overall fracture rate was observed when we compared the mean predicted scores after applying the KFRS with the observed risks after 7 years within each 10th of predicted risk. CONCLUSION: We developed a Korean specific prediction model for osteoporotic fractures. The KFRS was able to predict risk of fracture in the primary population without bone mineral density testing and is therefore suitable for use in both clinical setting and self-assessment. The website is available at http://www.nhis.or.kr. PMID- 27399598 TI - The ionic transport mechanism and coupling between the ion conduction and segmental relaxation processes of PEO20-LiCF3SO3 based ion conducting polymer clay composites. AB - A series of ion conducting polymer-clay composites has been prepared using a solution casting technique. Relaxation dynamics and the ionic transport mechanism are systematically studied employing broadband dielectric spectroscopy over a wide frequency and temperature range. Among different phenomenological and theoretical models for ion conduction in disordered ionic conductors, conductivity isotherm spectra are analysed using the modified Almond-West and random free energy barrier model. Conductivity scaling suggests that the ionic transport mechanism is independent of temperature, and a similar inference is also obtained using scaled electrical modulus spectra. DC conductivity along with conductivity and segmental relaxation time following the Vogel-Tammann-Fulcher relationship suggests coupling between the ionic transport and segmental relaxation processes. Electrical modulus and dielectric formalism are used to understand the conductivity and segmental relaxation processes, respectively. The presence of first and second universality in the ionic transport mechanism is discussed using the real part of conductivity spectra and dielectric loss spectra. The crossover between the first and second universality is explained using the Kramer-Kronig approach. The ion diffusion coefficient is investigated using Ratner's classical approach in combination with the modified Stokes Einstein relationship to correlate the coupled nature of the ion conduction mechanism and polymer segmental motion. PMID- 27399599 TI - The origin of emissive states of carbon nanoparticles derived from ensemble averaged and single-molecular studies. AB - At present, there is no consensus understanding on the origin of photoluminescence of carbon nanoparticles, particularly the so-called carbon dots. Providing comparative analysis of spectroscopic studies in solution and on a single-molecular level, we demonstrate that these particles behave collectively as fixed single dipoles and probably are the quantum emitter entities. Their spectral and lifetime heterogeneity in solutions is explained by variation of the local chemical environment within and around luminescence centers. Hence, the carbon dots possess a unique hybrid combination of fluorescence properties peculiar to dye molecules, their conjugates and semiconductor nanocrystals. It is proposed that their optical properties are due to generation of H-aggregate-type excitonic states with their coherence spreading over the whole nanoparticles. PMID- 27399600 TI - Remestemcel-L for the treatment of graft versus host disease. AB - INTRODUCTION: Remestemcel-L, a third-party, off-the-shelf preparation of bone marrow derived mesenchymal stromal cells (MSCs), has been developed for experimental use in acute graft-versus-host disease (aGvHD) and other immune mediated conditions. Several preclinical and clinical studies have indeed suggested the potential of human mesenchymal stromal cells (MSCs) as an effective treatment for steroid-refractory aGvHD. However, an unambiguous demonstration of efficacy is still lacking. Areas covered: This review critically examines the biologic rationale supporting MSCs use in aGvHD and analyzes the results of published clinical trials in this setting, with a particular focus on the potential benefits and drawbacks of Remestemcel-L. For this purpose, a systematic literature search was performed in PubMed using the following keywords: 'mesenchymal stromal cells', 'mesenchymal progenitor cells', 'multipotent stromal cells', 'mesenchymal cells', 'MSC', 'Remestemcel-L', 'Prochymal', and 'graft versus-host disease' or 'GvHD'. Expert commentary: Remestemcel-L represents a promising alternative to second-line immunosuppressive agents for the treatment of steroid-refractory aGvHD. Despite the safety and the favorable risk/benefit profile of this cell product, which has been demonstrated in several phase I-II studies, large and prospective randomized trials are required to confirm its efficacy in aGvHD and to define the optimal schedule of administration in terms of infusion timing, cell dose and pharmacological synergism. PMID- 27399601 TI - The Burden of Obesity, Elevated Blood Pressure, and Diabetes in Uninsured and Underinsured Adolescents. AB - BACKGROUND: Obesity, elevated blood pressure (BP), and diabetes mellitus are rising among the general U.S. adolescent population, but prevalence estimates are not available for uninsured or Medicaid populations. METHODS: This retrospective epidemiological study extracted 155,139 electronic medical records collected between 1998 and 2012 on patients aged 10-19 years, from a clinical population predominantly uninsured or insured by Medicaid. Age, sex, race, height, weight, BP, and insurance type were captured at first clinic visit. Classifications included obesity (>=95th body mass index percentile), elevated BP (>=90th percentile), and diabetes mellitus (ICD-9-250.xx). RESULTS: Among the 26,696 patients with complete data at first clinic visit, 24.4% were classified as obese and 39.5% had elevated BP. In logistic regression analyses, odds of obesity were significantly higher among uninsured versus commercially insured patients (odds ratio [OR]: 1.1 [95% confidence interval: 1.0-1.2]) and girls (OR: 1.3 [1.2 1.4]), but lower among older adolescents (for 15-17 years, OR: 0.7 [0.6-0.7]; for 18-19 years, OR: 0.7 [0.7-0.8]). Odds of elevated BP were significantly higher among Medicaid (OR: 1.1 [1.0-1.2]) and uninsured (OR: 1.2 [1.1-1.4]) versus commercially insured patients, but lower among African American versus White youth (OR: 0.9 [0.8-0.9]). Prevalence of type 1 diabetes was 1.46 per 1000 and prevalence of type 2 diabetes was 1.68 per 1000, with both occurring more often in girls versus boys and in Whites versus African Americans. CONCLUSION: In this low-income clinical population, prevalence of obesity and elevated BP were higher than national estimates. The provision of preventive healthcare to all Medicaid and uninsured youth should remain a priority. PMID- 27399602 TI - The Prevalence of Only-Child Status Among Children and Adolescents Referred to a Gender Identity Service Versus a Clinical Comparison Group. AB - Several studies indicate that homosexual males have a high proportion of older brothers compared to heterosexual males. Natal males with gender dysphoria who are likely to be homosexual also display this sibship pattern. Until recently, there was little evidence linking homosexuality and/or gender dysphoria in females to unique sibship characteristics. Two studies have indicated that natal female youth clinically referred for gender dysphoria are more likely to be only children (Schagen, Delemarre-van de Waal, Blanchard, & Cohen-Kettenis, 2012; VanderLaan, Blanchard, Wood, & Zucker, 2014). However, these studies did not include control groups of youth clinically referred for other reasons. Thus, it is unclear whether the increased likelihood of only-child status is specific to gender-referred natal females. This study compared only-child status among youth referred to a mental health service for gender dysphoria (778 males, 245 females) versus other reasons (783 males, 281 females). Prehomosexual gender-referred males were less likely to be only children than clinical controls. Contrary to previous findings, gender-referred females were not more likely to be only children, indicating that increased likelihood of only-child status is not specific to gender-referred females, but is characteristic of clinic-referred females more generally. PMID- 27399603 TI - Career, collections, reports and publications of Dr Francis Buchanan (later Hamilton), 1762-1829: natural history studies in Nepal, Burma (Myanmar), Bangladesh and India. Part 1. AB - During his 20-year career as a surgeon-naturalist with the British East India Company, Francis Buchanan (later Hamilton, known in botany as Buchanan-Hamilton and in ichthyology as Hamilton-Buchanan) undertook pioneering survey explorations in several diverse regions of the Indian subcontinent. A naturalist at heart, his collections of plants and animals are often the first from such regions, notably Nepal, Burma (Myanmar) and Bangladesh. Buchanan had wide-ranging interests beyond natural history, using his talent for observation and meticulous recording to amass a huge body of information on the lands and peoples he encountered. However, much of this information remains unpublished in his survey reports, journals and other manuscripts, and so his role in the building of knowledge for these areas has been under-appreciated. Although a keen and able botanist, it is ironic that his multitudinous botanical discoveries are particularly poorly known, with the vast majority of his material on this subject languishing unpublished in archival collections. These include his original records and working notes which show the methods he used when dealing with 'information overload' and arranging his syntheses ready for publication. Notable is his experimentation with Jussieu's Natural System for classifying his Nepalese plants, and his recognition of biogeographic links of the Nepalese flora with Europe and Japan - both ahead of his fellow countrymen in Britain and India. The life of Francis Buchanan awaits the attention of a biographer who can do justice to his many interests, activities and influences. This is the first of two papers covering his life, providing an empirical baseline for future research and correcting misinformation that abounds in the literature. These papers outline Buchanan's professional career, concentrating on his activities in the exploration of natural history, and placing them in the wider context of botanical research in India. PMID- 27399604 TI - Career development tips for today's nursing academic: bibliometrics, altmetrics and social media. AB - AIMS: A discussion of bibliometrics, altmetrics and social media for the contemporary nursing scholar and academic researcher. BACKGROUND: Today's nursing academic faces myriad challenges in balancing their daily life and, in recent years, academic survival has been increasingly challenged by the various research assessment exercises that evaluate the performance of knowledge institutions. As such, it is essential that today's nursing academic keep up to date with the core competencies needed for survival in a modern research career, particularly the intersecting triad of bibliometrics, altmetrics and social media. DESIGN: Discussion paper. DATA SOURCES: Published literature and relevant websites. IMPLICATIONS FOR NURSING: The rise of social media and altmetrics has important implications for contemporary nursing scholars who publish their research. Some fundamental questions when choosing a journal might be 'does it have a Twitter and/or Facebook site, or a blog (or all three)'; and 'does it have any other presence on social media, such as LinkedIn, Wikipedia, YouTube, ResearchGate and so on?' Another consequence of embracing social media is that individual academics should also develop their own strategies for promoting and disseminating their work as widely as possible. CONCLUSION: The rising importance of social media and altmetrics can no longer be ignored, and today's nursing academic now has another facet to consider in their scholarly activities. Despite the changing nature of research dissemination, however, it is still important to recognize the undoubted value of established knowledge dissemination routes (that being the peer-reviewed publication). PMID- 27399605 TI - Hierarchical Electrospun and Cooperatively Assembled Nanoporous Ni/NiO/MnOx/Carbon Nanofiber Composites for Lithium Ion Battery Anodes. AB - A facile method to fabricate hierarchically structured fiber composites is described based on the electrospinning of a dope containing nickel and manganese nitrate salts, citric acid, phenolic resin, and an amphiphilic block copolymer. Carbonization of these fiber mats at 800 degrees C generates metallic Ni encapsulated NiO/MnOx/carbon composite fibers with average BET surface area (150 m(2)/g) almost 3 times higher than those reported for nonporous metal oxide nanofibers. The average diameter (~900 nm) of these fiber composites is nearly invariant of chemical composition and can be easily tuned by the dope concentration and electrospinning conditions. The metallic Ni nanoparticle encapsulation of NiO/MnOx/C fibers leads to enhanced electrical conductivity of the fibers, while the block copolymers template an internal nanoporous morphology and the carbon in these composite fibers helps to accommodate volumetric changes during charging. These attributes can lead to lithium ion battery anodes with decent rate performance and long-term cycle stability, but performance strongly depends on the composition of the composite fibers. The composite fibers produced from a dope where the metal nitrate is 66% Ni generates the anode that exhibits the highest reversible specific capacity at high rate for any composition, even when including the mass of the nonactive carbon and Ni(0) in the calculation of the capacity. On the basis of the active oxides alone, near-theoretical capacity and excellent cycling stability are achieved for this composition. These cooperatively assembled hierarchical composites provide a platform for fundamentally assessing compositional dependencies for electrochemical performance. Moreover, this electrospinning strategy is readily scalable for the fabrication of a wide variety of nanoporous transition metal oxide fibers. PMID- 27399606 TI - Quilting as a generative activity: Studying those who make quilts for wounded service members. AB - A qualitative study of 24 quilters examined their experiences creating and delivering quilts to wounded service members who served in the Iraq and Afghanistan conflicts. Using Erikson's (1963) perspective on generativity and Baumeister and Vohs's (2002) theory of motivation as theoretical frameworks, along with McCracken's (1988) five-step analysis model, we looked at the part motivation played in this process. The results were that respondents wanted to supply quilts in response to their own family histories of military involvement, to support friends/acquaintances with family in the military, and to make a difference to those who seemed young and badly wounded. Some respondents described being affected by the reactions of quilt recipients and of healing from their own traumas and grief. PMID- 27399607 TI - Transforming MOFs for Energy Applications Using the Guest@MOF Concept. AB - As the world transitions from fossil fuels to clean energy sources in the coming decades, many technological challenges will require chemists and material scientists to develop new materials for applications related to energy conversion, storage, and efficiency. Because of their unprecedented adaptability, metal-organic frameworks (MOFs) will factor strongly in this portfolio. By utilizing the broad synthetic toolkit provided by the fields of organic and inorganic chemistry, MOF pores can be customized to suit a particular application. Of particular importance is the ability to tune the strength of the interaction between the MOF pores and guest molecules. By cleverly controlling these MOF-guest interactions, the chemist may impart new function into the Guest@MOF materials otherwise lacking in vacant MOF. Herein, we highlight the concept of the Guest@MOF as it relates to our efforts to develop these materials for energy-related applicatons. Our work in the areas of H2 and noble gas storage, hydrogenolysis of biomass, light-harvesting, and conductive materials will be discussed. Of relevance to light-harvesting applications, we report for the first time a postsynthetic modification strategy for increasing the loading of a light-sensitive electron-donor molecule in the pores of a functionalized MIL 101 structure. Through the demonstrated versatility of these approaches, we show that, by treating guest molecules as integral design elements for new MOF constructs, MOF science can have a significant impact on the advancement of clean energy technologies. PMID- 27399608 TI - The influence of multiple birth and bereavement on maternal and family outcomes 2 and 7years after very preterm birth. AB - BACKGROUND: Psychological distress has been reported by mothers of infants born very preterm (VPT) and by mothers of multiples (twins and triplets). This study examined the influence of i) multiple birth and ii) bereavement associated with a multifetal pregnancy, on mental health, parenting stress and family functioning for mothers of children born VPT across early childhood. METHODS: Participants were 162 mothers of 194 infants (129 singletons, 65 multiples) born at <30weeks' gestation or with a birth weight<1250g who completed questionnaires when their children were two and seven years corrected age. Fifteen mothers (9%) experienced bereavement associated with a multifetal pregnancy. Maternal mental health was assessed using the General Health Questionnaire at two years and Hospital Anxiety and Depression Scale at seven years. Parenting stress and family functioning were assessed using the Parenting Stress Index and Family Assessment Device. RESULTS: Maternal mental health, stress and family functioning were similar in mothers of VPT singletons and multiples. However compared with mothers who had not experienced bereavement, mothers who had were 3.6 times [95% confidence interval (95% CI) 1.05, 12.5] more likely to report elevated anxiety symptoms and 3.6 times [95% CI 1.05, 12.3] more likely to report elevated depressive symptoms when their VPT child was seven years old. CONCLUSIONS: The results of this study highlight the need for monitoring and offering ongoing support to bereaved mothers with surviving VPT children. However, within the context of VPT birth, multiple birth does not increase the risk for maternal psychological distress in early childhood. PMID- 27399609 TI - Fatality as a Feature of Medical Care. AB - Taking advantage of an interesting clinical scenario, we want to introduce a discussion about fatality in our daily practice and the need to accept that. An 80 year-old man with non-traumatic spontaneous bleeding tendency came to the clinics. Although being on warfarin as a consequence of primary thrombotic prophylaxis due to an atrial fibrillation, full assessment was performed. Not only the rare entity found on him, but also the severe complication that happened afterwards challenged clinicians and led them to risky treatment options. PMID- 27399610 TI - Anomalous Origin of a Stenosed Left Circumflex Coronary Artery in a Patient Presenting with Unstable Angina: A Case Report. AB - 73 year-old man presented to our emergency department with complaint of retrosternal chest pain since 2 day and admitted with diagnosis of unstable angina. He underwent diagnostic coronary angiography in which left circumflex artery (LCX) was not visualized during injection of the left coronary artery; indeed, it was originated, with common origin with RCA, from right coronary sinus of Valsalva. This case report is one of the uncommon cases with aberrant coronary arteries who presented with unstable angina. Moreover, coronary angiography with following coronary angioplasty was performed for him in a challenging course and angle for coronary intervention. PMID- 27399611 TI - Are migraine and non-migrainous headache risk factors for stroke in the elderly? Findings from a 12-year cohort follow-up. AB - BACKGROUND AND PURPOSE: There is evidence that migraine is a risk factor for stroke but little is known about this association in elderly people. Furthermore, non-migrainous headache (NMH) has received little attention despite being the most frequently reported type of headache. Late-life migraine and NMH were examined as candidate risk factors for stroke in a community-dwelling elderly sample over a 12-year follow-up. METHODS: One thousand nine hundred and nineteen non-institutionalized subjects aged 65+, without dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, DSM-IV criteria) and with no stroke history at baseline, were drawn from the Three-City Montpellier cohort (recruitment 1999-2001) for longitudinal analysis. Ischaemic and haemorrhagic stroke was reported at baseline and at each of the five follow-ups, with cases validated by a panel of experts, according to ICD-10 criteria (International Classification of Diseases, 10th revision). Migraine and NMH were determined at baseline during a neurological interview and examination using 1988 International Headache Society criteria. RESULTS: A total of 110 (5.4%) cases of migraine and 179 (8.9%) cases of NMH were identified at baseline. During the median 8.8-year follow-up, incident stroke was observed in 1.9% of baseline migrainers, 6.2% of NMH and 3.6% of those with no lifetime history of headache. Cox proportional hazard models indicated that migraine was not a risk factor for stroke; however, NMH sufferers were twice as likely to have a stroke (hazard ratio 2.00, 95% confidence interval 1.00-3.93, P = 0.049). CONCLUSIONS: This study is one of the first to suggest that late-life NMH rather than migraine could be an independent risk factor for stroke and a warning sign. The incidence of stroke in elderly migrainers, seldom reported, is particularly low. PMID- 27399612 TI - Ventral striatal hyperconnectivity during rewarded interference control in adolescents with ADHD. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is characterized by cognitive deficits (e.g., interference control) and altered reward processing. Cognitive control is influenced by incentive motivation and according to current theoretical models, ADHD is associated with abnormal interactions between incentive motivation and cognitive control. However, the neural mechanisms by which reward modulates cognitive control in individuals with ADHD are unknown. METHOD: We used event-related functional resonance imaging (fMRI) to study neural responses during a rewarded Stroop color-word task in adolescents (14-17 years) with ADHD (n = 25; 19 boys) and healthy controls (n = 33; 22 boys). RESULTS: Adolescents with ADHD showed increased reward signaling within the superior frontal gyrus and ventral striatum (VS) relative to controls. Importantly, functional connectivity analyses revealed a hyperconnectivity between VS and motor control regions in the ADHD group, as a function of reward-cognitive control integration. Connectivity was associated with performance improvement in controls but not in the ADHD group, suggesting inefficient connectivity. CONCLUSION: Adolescents with ADHD show increased neural sensitivity to rewards and its interactions with interference control in VS and motor regions, respectively. The findings support theoretical models of altered reward-cognitive control integration in individuals with ADHD. PMID- 27399613 TI - Performance enhancement of polyvinyl chloride ultrafiltration membrane modified with graphene oxide. AB - A novel polyvinyl chloride (PVC) membrane was modified with graphene oxide (GO) via phase inversion method to improve its hydrophilicity and mechanical properties. The GO presented a large amount of hydrophilic groups after the modification through the modified Hummers method. It was observed that with the addition of low fraction of GO powder, the GO/PVC hybrid membranes exhibited a significant enhancement in hydrophilicity, water flux, and mechanical properties. With optimal dosage (0.1wt%), the pure water flux of GO/PVC membrane increased from 232.6L/(m(2)hbar) to 430.0L/(m(2)hbar) and the tensile strength increased from 231.3cN to 305.3cN. The improved properties of the PVC/GO hybrid membranes are mainly attributed to the strong hydrophilicity of functional groups on the GO surface, indicating that GO has a promising candidate for modification of PVC ultrafiltration membranes in wastewater treatment. PMID- 27399614 TI - Photocatalytic and antibacterial activity of cadmium sulphide/zinc oxide nanocomposite with varied morphology. AB - Nanocomposites with multifunctional application prospects have already dragged accelerating interests of materials scientists. Here we present CdS/ZnO nanocomposites with different morphology engineering the precursor molar ratio in a facile wet chemical synthesis route. The materials were structurally and morphologically characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray analysis (EDX) and high resolution transmission electron microscopy (HRTEM). The growth mechanism of the composite structure with varying molar ratio is delineated with oriented attachment self assemble techniques. Photocatalytic activity of CdS/ZnO nanocomposites with varying morphology were explored for the degradation of rhodamine B (RhB) dye in presence of visible light irradiation and the results reveal that the best catalytic performance arises in CdS/ZnO composite with 1: 1 ratio. The antibacterial efficiency of all nanocomposites were investigated on Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia without light irradiation. Antibacterial activity of CdS/ZnO nanocomposites were studied using the bacteriological test-well diffusion agar method and results showed significant antibacterial activity in CdS/ZnO composite with 1:3 ratio. Overall, CdS/ZnO nanocomposites excel in different potential applications, such as visible light photocatalysis and antimicrobial activity with their tuneable structure. PMID- 27399615 TI - CO oxidation over gold supported on Cs, Li and Ti-doped cryptomelane materials. AB - Cryptomelane-type manganese oxides were synthesized by redox reaction under acid and reflux conditions. Different metals (cesium, lithium and titanium) were incorporated into the tunnel structure by the ion-exchange technique. Gold was loaded onto these materials (1wt%) by a double impregnation method. The obtained catalysts were characterized by high-resolution transmission electron microscopy, energy-dispersive X-ray spectrometry, scanning electron microscopy, X-ray diffraction and temperature-programmed reduction. The catalytic activity of these materials was evaluated in the oxidation of carbon monoxide. The incorporation of Cs, Li or Ti into cryptomelane was detrimental in terms of catalytic activity. Further addition of gold to cryptomelane doped materials significantly improved the catalytic performance, especially for Cs-K-OMS-2 and Li-K-OMS-2 (to a smaller extent). Addition of gold to the Ti containing material did not show a significant improvement. The observed trends are related to the effect of gold on samples reducibility and to the gold particle size. The lattice oxygen can also be considered accountable for the activity of the materials, since the most active cryptomelane catalysts are those with higher lattice oxygen donating ability for the oxidation of the CO molecule. PMID- 27399616 TI - A facile synthesis of gold micro/nanostructures at the interface of 1,3 dibutylimidazolium bis(trifluoromethylsulfonyl)imide and water. AB - The development of a simple, template-free, and one-step strategy to synthesize nanostructured Au architectures with fascinating morphology is highly desirable and technically important due to their valuable applications in varied fields. In this work, the "green" strategy of "tunable ionic liquids-water (ILs-H2O) interfacial synthesis" developed previously by us is utilized for feasible synthesis of gold needle mushroom-like micro/nanostructures at the 1,3 dibutylimidazolium bis(trifluoromethylsulfonyl)imide ([C4bim][Tf2N]) - water interface and ambient conditions. The as-obtained gold needle mushrooms (AuNMs) have been characterized and analyzed systemically by scanning electron microscopy, X-ray powder diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. It is shown that the as-prepared AuNMs can be used as substrates to perform surface enhanced Raman scattering (SERS) investigation with striking SERS sensitivity. By employing ILs with different alkyl chain lengths of the imidazolium cations and/or different nature of anions, Au nanomaterials with diverse morphologies can be easily prepared at different ILs-H2O interfaces. Based on the analysis of the control experiments, the growth and formation of AuNMs at the [C4bim][Tf2N]-H2O interface have been discussed. PMID- 27399617 TI - pH and redox-operated nanovalve for size-selective cargo delivery on hollow mesoporous silica spheres. AB - A pH and redox dual-responsive nanovalve with a long stalk was introduced on the surface of hollow mesoporous silica nanoparticles (HMSs-S1) to achieve cargo size selectivity delivery. The responsive nanovalve was designed by constructing of a stalk/beta-cyclodextrins (CDs) supramolecular complex, which is based on an acid labile acetal group and the host-guest interactions between beta-cyclodextrins and ferrocenyl moiety (Fc). With stimulation by different pH and H2O2, Rhodamine 6G showed well-responsive behavior. On account of the long stalks of nanovalve, doxorubicin hydrochloride and 5-fluorouracil with different sized cargos are encapsulated in HMSs-S1 to test its behavior of cargo size-selective delivery. Moreover the HMSs-S2 with a short stalk based on beta-CDs/Fc inclusion complex is synthesized to load small sized 5-FU drug as contrast experiment. Compared with HMSs-S2, HMSs-S1 is compatible with larger drug molecules such as Rhodamine 6G (R6G) and doxorubicin hydrochloride (DOX), while small sized 5-fluorouracil (5 FU) is unable to be sealed by the nanovalve. Dual responsiveness and drug size selectivity make mechanized HMSs possess potential applications in drug delivery system. PMID- 27399618 TI - CdS/CdSe quantum dots and ZnPc dye co-sensitized solar cells with Au nanoparticles/graphene oxide as efficient modified layer. AB - Co-sensitization by using two or more sensitizers with complementary absorption spectra to expand the spectral response range is an effective approach to enhance device performance of quantum dot sensitized solar cells (QDSSCs). To improve the light-harvesting in the visible/near-infrared (NIR) region, organic dye zinc phthalocyanine (ZnPc) was combined with CdS/CdSe quantum dots (QDs) for co sensitized solar cells based on ZnO inverse opals (IOs) as photoanode. The resulting co-sensitized device shows an efficient panchromatic spectral response feature to ~750nm and presents an overall conversion efficiency of 4.01%, which is superior to that of the individual ZnPc-sensitized solar cells and CdS/CdSe sensitized solar cells. Meanwhile, an Au nanoparticles/graphene oxide (Au NPs/GO) composite layer was successfully prepared to modify Cu2S counter electrode for the co-sensitized solar cells. Reducing the carrier recombination process by GO and catalytic process of Au NPs leads to increased power conversion efficiency(PCE) from 4.01 to 4.60% and sustainable stability remains ~85% of its original value after 60min light exposure. In this paper, introduction of the organic dyes as co-sensitizer and Au NPs/GO as counter electrode modified layer has been proved to be an effective route to improve the performance of QDSSCs. PMID- 27399619 TI - Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles. AB - A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C-C bond formation proceeding through a free radical mechanism. PMID- 27399621 TI - Editor's notes. PMID- 27399620 TI - Binding to Bovine Serum Albumin Protects beta-Carotene against Oxidative Degradation. AB - Binding to bovine serum albumin (BSA) was found to protect beta-carotene (beta Car) dissolved in air-saturated phosphate buffer solution/tetrahydrofuran (9:1, v/v) efficiently against photobleaching resulting from laser flash excitation at 532 nm. From dependence of the relative photobleaching yield upon the BSA concentration, an association constant of Ka = 4.67 * 10(5) L mol(-1) for beta Car binding to BSA was determined at 25 degrees C. Transient absorption spectroscopy confirmed less bleaching of beta-Car on the microsecond time scale in the presence of BSA, while kinetics of triplet-state beta-Car was unaffected by the presence of oxygen. The protection of beta-Car against this type of reaction seems accordingly to depend upon dissipation of excitation energy from an excited state into the protein matrix. Static quenching of BSA fluorescence by beta-Car had a Stern-Volmer constant of Ksv = 2.67 * 10(4) L mol(-1), with DeltaH = 17 kJ mol(-1) and DeltaS = 142 J mol(-1) K(-1) at 25 degrees C. Quenching of tryptophan (Trp) fluorescence by beta-Car suggests involvement of Trp in binding of beta-Car to BSA through hydrophobic interaction, while the lower value for the Stern-Volmer constant Ksv compared to the binding constant, Ka, may indicate involvement of beta-Car aggregates. Bound beta-Car increased the random coil fraction of BSA at the expense of alpha-helix, as shown by circular dichroism, affecting the beta-Car configuration, as shown by Raman spectroscopy. PMID- 27399623 TI - Brief reports. PMID- 27399622 TI - Letters. PMID- 27399624 TI - A need to know. PMID- 27399625 TI - Escape, Joy, Harmony-All in an Hour's Run. PMID- 27399627 TI - Women's Response to Army Training. PMID- 27399626 TI - The Capabilities of Women. PMID- 27399628 TI - Lower Extremities Are Site of Most Soccer Injuries. PMID- 27399630 TI - Osgood-Schlatter Disease. PMID- 27399629 TI - Evaluation and Treatment of Lateral Ankle Sprains. PMID- 27399631 TI - Osgood-Schlatter Disease: The Painful Puzzler. PMID- 27399632 TI - Cme credit quiz. PMID- 27399634 TI - The Top of the World-'There Were No More Steps'. PMID- 27399635 TI - Sportsmedicine News in Perspective. PMID- 27399637 TI - Science and the Future of Sports. PMID- 27399636 TI - Medical Care of a Championship Soccer Club. PMID- 27399638 TI - Guidelines for Knee Rehabilitation. PMID- 27399639 TI - Running Physicians Called Fitness Testimonials. PMID- 27399640 TI - Yearn to Sail? For Many, It's a Breeze. PMID- 27399643 TI - The brain that changed neurology: Broca's 1861 case of aphasia. PMID- 27399642 TI - Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model. AB - We present the AMBER ff15ipq force field for proteins, the second-generation force field developed using the Implicitly Polarized Q (IPolQ) scheme for deriving implicitly polarized atomic charges in the presence of explicit solvent. The ff15ipq force field is a complete rederivation including more than 300 unique atomic charges, 900 unique torsion terms, 60 new angle parameters, and new atomic radii for polar hydrogens. The atomic charges were derived in the context of the SPC/Eb water model, which yields more-accurate rotational diffusion of proteins and enables direct calculation of nuclear magnetic resonance (NMR) relaxation parameters from molecular dynamics simulations. The atomic radii improve the accuracy of modeling salt bridge interactions relative to contemporary fixed charge force fields, rectifying a limitation of ff14ipq that resulted from its use of pair-specific Lennard-Jones radii. In addition, ff15ipq reproduces penta alanine J-coupling constants exceptionally well, gives reasonable agreement with NMR relaxation rates, and maintains the expected conformational propensities of structured proteins/peptides, as well as disordered peptides-all on the microsecond (MUs) time scale, which is a critical regime for drug design applications. These encouraging results demonstrate the power and robustness of our automated methods for deriving new force fields. All parameters described here and the mdgx program used to fit them are included in the AmberTools16 distribution. PMID- 27399644 TI - A Culture-Centered Approach to Improving Healthy Trans-Patient-Practitioner Communication: Recommendations for Practitioners Communicating withTrans Individuals. AB - The following manuscript explores trans individuals' lived experiences with practitioners and the types of advice they suggested be provided to practitioners treating trans patients to improve the trans-patient-practitioner relationship. Thirteen semi-structured qualitative interviews were conducted with individuals who self-identified as trans. Interviews were analyzed using thematic analysis (Braun & Clarke, 2006; Owen, 1984). Data analysis revealed that changes in practitioner's communication behavior during office visits as well as modifications to office logistics and e-health particulars would contribute to a healthy communication environment. Interviewees explained that these variations may potentially improve trans-patient-practitioner communication. We conclude by offering practical and theoretical implications as well as areas of future research for trans health communication. PMID- 27399645 TI - Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. AB - Efficient delivery of therapeutics across the neuroprotective blood-brain barrier (BBB) remains a formidable challenge for central nervous system drug development. High-fidelity in vitro models of the BBB could facilitate effective early screening of drug candidates targeting the brain. In this study, we developed a microfluidic BBB model that is capable of mimicking in vivo BBB characteristics for a prolonged period and allows for reliable in vitro drug permeability studies under recirculating perfusion. We derived brain microvascular endothelial cells (BMECs) from human induced pluripotent stem cells (hiPSCs) and cocultured them with rat primary astrocytes on the two sides of a porous membrane on a pumpless microfluidic platform for up to 10 days. The microfluidic system was designed based on the blood residence time in human brain tissues, allowing for medium recirculation at physiologically relevant perfusion rates with no pumps or external tubing, meanwhile minimizing wall shear stress to test whether shear stress is required for in vivo-like barrier properties in a microfluidic BBB model. This BBB-on-a-chip model achieved significant barrier integrity as evident by continuous tight junction formation and in vivo-like values of trans endothelial electrical resistance (TEER). The TEER levels peaked above 4000 Omega . cm2 on day 3 on chip and were sustained above 2000 Omega . cm2 up to 10 days, which are the highest sustained TEER values reported in a microfluidic model. We evaluated the capacity of our microfluidic BBB model to be used for drug permeability studies using large molecules (FITC-dextrans) and model drugs (caffeine, cimetidine, and doxorubicin). Our analyses demonstrated that the permeability coefficients measured using our model were comparable to in vivo values. Our BBB-on-a-chip model closely mimics physiological BBB barrier functions and will be a valuable tool for screening of drug candidates. The residence time-based design of a microfluidic platform will enable integration with other organ modules to simulate multi-organ interactions on drug response. Biotechnol. Bioeng. 2017;114: 184-194. (c) 2016 Wiley Periodicals, Inc. PMID- 27399646 TI - Personal Actions to Minimize Mosquito-Borne Illnesses, Including Zika Virus. PMID- 27399648 TI - Extremely low-frequency electromagnetic fields: A possible non-invasive therapeutic tool for spinal cord injury rehabilitation. AB - Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration. The latter involves a range of events namely cellular disturbance, homeostatic imbalance, ionic and neurotransmitters derangement that ultimately result in loss of sensorimotor functions. The targets for improving function after spinal cord injury (SCI) are mainly directed toward limiting these secondary injury events. Extremely low-frequency electromagnetic field (ELF-EMF) is a possible non-invasive therapeutic intervention for SCI rehabilitation which has the potential to constrain the secondary injury-induced events. In the present review, we discuss the effects of ELF-EMF on experimental and clinical SCI as well as on biological system. PMID- 27399647 TI - Emerging developmental genetic model systems in holometabolous insects. AB - The number of insect species that are amenable to functional genetic studies is growing rapidly and provides many new research opportunities in developmental and evolutionary biology. The holometabolous insects represent a disproportionate percentage of animal diversity and are thus well positioned to provide model species for a wide variety of developmental processes. Here we discuss emerging holometabolous models, and review some recent breakthroughs. For example, flies and midges were found to use structurally unrelated long-range pattern organizers, butterflies and moths revealed extensive pattern formation during oogenesis, new imaging possibilities in the flour beetle Tribolium castaneum showed how embryos break free of their extraembryonic membranes, and the complex genetics governing interspecies difference in head shape were revealed in Nasonia wasps. PMID- 27399651 TI - Development of Droplet Microfluidics Enabling High-Throughput Single-Cell Analysis. AB - This article reviews recent developments in droplet microfluidics enabling high throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic droplets enabling single-cell proteomic analysis; (4) microfluidic droplets enabling single-cell genomic analysis; and (5) integrated microfluidic droplet systems enabling single-cell screening. We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on key performances of throughput, multifunctionality, and absolute quantification. PMID- 27399649 TI - Enhanced neointimal fibroblast, myofibroblast content and altered extracellular matrix composition: Implications in the progression of human peripheral artery restenosis. AB - BACKGROUND AND AIMS: Neointimal cellular proliferation of fibroblasts and myofibroblasts is documented in coronary artery restenosis, however, their role in peripheral arterial disease (PAD) restenosis remains unclear. Our aim was to investigate the role of fibroblasts, myofibroblasts, and collagens in restenotic PAD. METHODS: Nineteen PAD restenotic plaques were compared with 13 de novo plaques. Stellate cells (H&E), fibroblasts (FSP-1), myofibroblasts (alpha actin/vimentin/FSP-1), cellular proliferation (Ki-67), and apoptosis (caspase-3 with poly ADP-ribose polymerase) were evaluated by immunofluorescence. Collagens were evaluated by picro-sirius red stain with polarization microscopy. Smooth muscle myosin heavy chain (SMMHC), IL-6 and TGF-beta cytokines were analyzed by immunohistochemistry. RESULTS: Restenotic plaques demonstrated increased stellate cells (2.7 +/- 0.15 vs.1.3 +/- 0.15) fibroblasts (2282.2 +/- 85.9 vs. 906.4 +/- 134.5) and myofibroblasts (18.5 +/- 1.2 vs.10.6 +/- 1.0) p = 0.0001 for all comparisons. In addition, fibroblast proliferation (18.4% +/- 1.2 vs.10.4% +/- 1.1; p = 0.04) and apoptosis (14.6% +/- 1.3 vs.11.2% +/- 0.6; p = 0.03) were increased in restenotic plaques. Finally, SMMHC (2.6 +/- 0.12 vs.1.4 +/- 0.15; p = 0.0001), type III collagen density (0.33 +/- 0.06 vs. 0.17 +/- 0.07; p = 0.0001), IL-6 (2.08 +/- 1.7 vs.1.03 +/- 2.0; p = 0.01), and TGF-beta (1.80 +/- 0.27 vs. 1.11 +/- 0.18; p = 0.05) were increased in restenotic plaques. CONCLUSIONS: Our study suggests proliferation and apoptosis of fibroblast and myofibroblast with associated increase in type III collagen may play a role in restenotic plaque progression. Understanding pathways involved in proliferation and apoptosis in neointimal cells, may contribute to future therapeutic interventions for the prevention of restenosis in PAD. PMID- 27399650 TI - Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse. AB - Host genetic variations play an important role in several pathogenic diseases, and we have previously provided strong evidences that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive Group A Streptococcus (GAS) infections, including sepsis and necrotizing soft tissue infections (NSTIs). Our initial studies with conventional mouse strains revealed that host genetic variations and sex differences play an important role in orchestrating the severity, susceptibility and outcomes of NSTIs. To understand the complex genetic architecture of NSTIs, we utilized an unbiased, forward systems genetics approach in an advanced recombinant inbred (ARI) panel of mouse strains (BXD). Through this approach, we uncovered interactions between host genetics, and other non-genetic cofactors including sex, age and body weight in determining susceptibility to NSTIs. We mapped three NSTIs-associated phenotypic traits (i.e., survival, percent weight change, and lesion size) to underlying host genetic variations by using the WebQTL tool, and identified four NSTIs-associated quantitative genetic loci (QTL) for survival on mouse chromosome (Chr) 2, for weight change on Chr 7, and for lesion size on Chr 6 and 18 respectively. These QTL harbor several polymorphic genes. Identification of multiple QTL highlighted the complexity of the host-pathogen interactions involved in NSTI pathogenesis. We then analyzed and rank-ordered host candidate genes in these QTL by using the QTLminer tool and then developed a list of 375 candidate genes on the basis of annotation data and biological relevance to NSTIs. Further differential expression analyses revealed 125 genes to be significantly differentially regulated in susceptible strains compared to their uninfected controls. Several of these genes are involved in innate immunity, inflammatory response, cell growth, development and proliferation, and apoptosis. Additional network analyses using ingenuity pathway analysis (IPA) of these 125 genes revealed interleukin-1 beta network as key network involved in modulating the differential susceptibility to GAS NSTIs. PMID- 27399652 TI - New Perspectives on the Use of Phytochemicals as an Emergent Strategy to Control Bacterial Infections Including Biofilms. AB - The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs not as vulnerable as the current ones to bacterial resistance mechanisms, and also able to target bacteria in biofilms. Natural products, especially those obtained from plants, have proven to be outstanding compounds with unique properties, making them perfect candidates for these much-needed therapeutics. This review presents the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. Further, the difficulties associated with the use of the existing antibiotics in the treatment of biofilm-related infections are described. To counteract the biofilm resistance problems, innovative strategies are suggested based on literature data. Among the proposed strategies, the use of phytochemicals to inhibit or eradicate biofilms is highlighted. An overview on the use of phytochemicals to interfere with bacterial quorum sensing (QS) signaling pathways and underlying phenotypes is provided. The use of phytochemicals as chelating agents and efflux pump inhibitors is also reviewed. PMID- 27399654 TI - Radical Smiles Rearrangement: An Update. AB - Over the decades the Smiles rearrangement and its variants have become essential synthetic tools in modern synthetic organic chemistry. In this mini-review we summarized some very recent results of the radical version of these rearrangements. The selected examples illustrate the synthetic power of this approach, especially if it is incorporated into a domino process, for the preparation of polyfunctionalized complex molecules. PMID- 27399653 TI - Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes. AB - Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO 1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling. PMID- 27399655 TI - A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation. AB - The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 * 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 MUm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip. PMID- 27399656 TI - Biotransformation of Resveratrol: New Prenylated trans-Resveratrol Synthesized by Aspergillus sp. SCSIOW2. AB - Arahypin-16 (1), a new prenylated resveratrol with a unique dihydrobenzofuran ring, has been isolated as a microbial metabolite of resveratrol (2) from whole cell fermentation of Aspergillus sp. SCSIOW2. The stereochemistry of 1 was determined by ECD calculations. 1 showed about half of the extracellular radical scavenging effect (IC50 = 161.4 MUM) compared with resveratrol (IC50 = 80.5 MUM), while on biomembranes it exhibited the same range of protection effects against free radicals generated from AAPH (IC50 = 78.6 MUM and 87.9 MUM). PMID- 27399657 TI - The Pleiotropic Antibacterial Mechanisms of Ursolic Acid against Methicillin Resistant Staphylococcus aureus (MRSA). AB - (1) BACKGROUND: Several triterpenoids were found to act synergistically with classes of antibiotic, indicating that plant-derived chemicals have potential to be used as therapeutics to enhance the activity of antibiotics against multidrug resistant pathogens. However, the mode of action of triterpenoids against bacterial pathogens remains unclear. The objective of this study is to evaluate the interaction between ursolic acid against methicillin-resistant Staphylococcus aureus (MRSA); (2) METHODS: The ability of ursolic acid to damage mammalian and bacterial membranes was examined. The proteomic response of methicillin-resistant S. aureus in ursolic acid treatment was investigated using two-dimensional (2D) proteomic analysis; (3) RESULTS: Ursolic acid caused the loss of staphylococcal membrane integrity without hemolytic activity. The comparison of the protein pattern of ursolic acid-treated and normal MRSA cells revealed that ursolic acid affected a variety of proteins involved in the translation process with translational accuracy, ribonuclease and chaperon subunits, glycolysis and oxidative responses; (4) CONCLUSION: The mode of action of ursolic acid appears to be the influence on the integrity of the bacterial membrane initially, followed by inhibition of protein synthesis and the metabolic pathway. These findings reflect that the pleiotropic effects of ursolic acid against MRSA make it a promising antibacterial agent in pharmaceutical research. PMID- 27399658 TI - Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine. AB - Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S. National Institutes of Health. However, the limited availability of effective medications and the high cost are still the major barriers for many cancer patients. Thus alternative approaches such as herbal medicines could be a feasible and less costly option. Unfortunately, scientific evidence for the efficacy of a majority of herbal medicines is still lacking and their development to meet FDA approval or other regulatory agencies is a big challenge. However, herbal medicines may be able to play an important role in precision medicine or personalized medicine. This review will focus on the existing and future technologies that could speed the development of herbal products for treatment of resistant cancer in individual patients. Specifically, it will concentrate on reviewing the phenotypic (activity based) rather than genotypic (mechanism based) approach to develop herbal medicine useful for personalized cancer chemotherapy. PMID- 27399659 TI - beta-Keto-enol Tethered Pyridine and Thiophene: Synthesis, Crystal Structure Determination and Its Organic Immobilization on Silica for Efficient Solid-Liquid Extraction of Heavy Metals. AB - Molecules bearing beta-keto-enol functionality are potential candidates for coordination chemistry. Reported herein is the first synthesis and use of a novel designed ligand based on beta-keto-enol group embedded with pyridine and thiophene moieties. The product was prepared in a one-step procedure by mixed Claisen condensation and was characterized by EA, m/z, FT-IR, (1H, (13)C) NMR and single-crystal X-ray diffraction analysis. The new structure was grafted onto silica particles to afford a chelating matrix which was well-characterized by EA, FT-IR, solid-state (13)C-NMR, BET, BJH, SEM and TGA. The newly prepared organic inorganic material was used as an adsorbent for efficient solid-phase extraction (SPE) of Cu(II), Zn(II), Cd(II) and Pb(II) from aqueous solutions and showed a capture capacity of 104.12 mg.g(-1), 98.90 mg.g(-1), 72.02 mg.g(-1), and 65.54 mg.g(-1), respectively. The adsorption capacity was investigated, in a batch method, using time of contact, pH, initial concentration, kinetics (Langmuir and Freundlich models), and thermodynamic parameters (DeltaG degrees , DeltaH degrees and DeltaS degrees ) of the system effects. PMID- 27399660 TI - In Vitro Reversible and Time-Dependent CYP450 Inhibition Profiles of Medicinal Herbal Plant Extracts Newbouldia laevis and Cassia abbreviata: Implications for Herb-Drug Interactions. AB - This study evaluated the effects of Newbouldia laevis and Cassia abbreviata extracts on CYP450 enzyme activity. Recombinant CYP450 enzyme and fluorogenic substrates were used for evaluating inhibition, allowing the assessment of herb drug interactions (HDI). Phytochemical fingerprinting was performed using UPLC MS. The herbal extracts were risk ranked for HDI based on the IC50 values determined for each CYP enzyme. Newbouldia laevis inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities with Ki of 2.84 ug/mL, 1.55 ug/mL, and 1.23 ug/mL, respectively. N. laevis exhibited a TDI (4.17) effect on CYP1A2 but not CYP2C9 and CYP2C19 enzyme activities. Cassia abbreviata inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities showing a Ki of 4.86 ug/mL, 5.98 ug/mL, and 1.58 ug/mL, respectively. TDI potency assessment for Cassia abbreviata showed it as a potential TDI candidate (1.64) for CYP1A2 and CYP2C19 (1.72). UPLC-MS analysis showed that Newbouldia laevis and Cassia abbreviata possess polyphenols that likely give them their therapeutic properties; some of them are likely to be responsible for the observed inhibition. The observations made in this study suggest the potential for these herbal compounds to interact, especially when co administered with other medications metabolized by these CYP450 enzymes. PMID- 27399661 TI - Inhibitory Activities of Phenolic Compounds Isolated from Adina rubella Leaves Against 5alpha-Reductase Associated with Benign Prostatic Hypertrophy. AB - Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti oxidative and anti-inflammatory activities and 5alpha-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy (BPH). Repeated chromatographic isolation of an 80% acetone extract of AR leaves yielded seven phenolic compounds: caffeic acid (1), chlorogenic acid (2), methyl chlorogenate (3), quercetin-3-rutinoside (4), kaempferol-3-O-alpha-l-rhamnopyranosyl-(1->6)-beta-d-glucopyranoside (5), hyperoside (6), and grandifloroside (7). Compound 7 is a novel compound in AR. Caffeoyl derivatives 1-3 and 7 showed good anti-oxidative activities. In particular, caffeic acid (1) and grandifloroside (7) showed potent anti inflammatory activities, and 7 also exhibited potent inhibitory activity against TNF-alpha and 5alpha-reductase. Our results show that the extract and grandifloroside (7) from leaves of AR might be developed as a source of potent anti-oxidative and anti-inflammatory agents and therapeutic agent for BPH. PMID- 27399662 TI - Auto-Tandem Catalysis in Ionic Liquids: Synthesis of 2-Oxazolidinones by Palladium-Catalyzed Oxidative Carbonylation of Propargylic Amines in EmimEtSO4. AB - A convenient carbonylative approach to 2-oxazolidinone derivatives carried out using an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, EmimEtSO4) as the solvent is presented. It is based on the sequential concatenation of two catalytic cycles, both catalyzed by the same metal species (auto-tandem catalysis): the first cycle corresponds to the oxidative monoaminocarbonylation of the triple bond of propargylic amines to give the corresponding 2-ynamide intermediates, while the second one involves the cyclocarbonylation of the latter to yield 2-(2-oxooxazolidin-5-ylidene)-acetamides. Reactions are carried out using a simple catalytic system consisting of PdI2 in conjunction with an excess of KI, and the catalyst/solvent system could be recycled several times without appreciable loss of activity after extraction of the organic product with Et2O. PMID- 27399663 TI - A High-Throughput Automated Microfluidic Platform for Calcium Imaging of Taste Sensing. AB - The human enteroendocrine L cell line NCI-H716, expressing taste receptors and taste signaling elements, constitutes a unique model for the studies of cellular responses to glucose, appetite regulation, gastrointestinal motility, and insulin secretion. Targeting these gut taste receptors may provide novel treatments for diabetes and obesity. However, NCI-H716 cells are cultured in suspension and tend to form multicellular aggregates, preventing high-throughput calcium imaging due to interferences caused by laborious immobilization and stimulus delivery procedures. Here, we have developed an automated microfluidic platform that is capable of trapping more than 500 single cells into microwells with a loading efficiency of 77% within two minutes, delivering multiple chemical stimuli and performing calcium imaging with enhanced spatial and temporal resolutions when compared to bath perfusion systems. Results revealed the presence of heterogeneity in cellular responses to the type, concentration, and order of applied sweet and bitter stimuli. Sucralose and denatonium benzoate elicited robust increases in the intracellular Ca(2+) concentration. However, glucose evoked a rapid elevation of intracellular Ca(2+) followed by reduced responses to subsequent glucose stimulation. Using Gymnema sylvestre as a blocking agent for the sweet taste receptor confirmed that different taste receptors were utilized for sweet and bitter tastes. This automated microfluidic platform is cost effective, easy to fabricate and operate, and may be generally applicable for high-throughput and high-content single-cell analysis and drug screening. PMID- 27399664 TI - Biochemical Constituents and in Vitro Antioxidant and Anticholinesterase Potential of Seeds from Native Korean Persimmon Genotypes. AB - In the current study, the functional and biochemical potential of the seeds of four persimmon cultivars (PC1, PC2, PC3 and PC4) and their role against oxidative stress and acetylcholinesterase (AChE) inhibition were evaluated. In terms of biochemical compositions, free amino acids, fatty acids and organic acids analysis was performed. The free amino acids ranged from 2617.31 (PC2) to 3773.01 MUg?g(-1) dry weight (PC4). Oleic acid and linoleic acid were the principal fatty acids, which were significantly higher in PC4 and PC1, respectively. PC4 presented the highest amount of organic acid content (4212 mg?kg(-1)), whereas PC2 presented the lowest (2498 mg?kg(-1)). PC2 contained higher total phenolic content and flavonoid content, whereas PC3 had the lowest amount as compared to other cultivars. The in vitro DPPH, ABTS and superoxide anion radicals scavenging activity increased in a dose-dependent manner, whereas PC2 showed significantly higher scavenging activities as compared to PC1, PC2 and PC4 types. In the case of AChE inhibition, PC4 showed a moderate activity (67.34% +/- 1.8%). In conclusion, the current findings reveal that the studied persimmon seeds cultivars are a source of bioactive natural antioxidants and AChE inhibitors. Such natural products could be employed in pharmaceutical and food industries, whilst can also be considered for the treatment of neurodegenerative diseases such as Alzheimer's. PMID- 27399665 TI - Marine Natural Products as Models to Circumvent Multidrug Resistance. AB - Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds. PMID- 27399666 TI - Cytotoxic Alkaloids from the Stem of Xylopia laevigata. AB - Xylopia laevigata (Annonaceae), known locally as "meiu" or "pindaiba", is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (-)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+) xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (-)-xylopinine, (+) norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (-)-corytenchine, (+) discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+) norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G2/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids. PMID- 27399667 TI - Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions. AB - Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5 trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications. PMID- 27399668 TI - Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity. AB - Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl4-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4'-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 uM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G2/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G2/M phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 uM) was examined on isolated aortic rings. Co-incubation with 6 gingerol (30 uM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics. PMID- 27399669 TI - Using Low Temperature Photoluminescence Spectroscopy to Investigate CH3NH3PbI3 Hybrid Perovskite Degradation. AB - Investigating the stability and evaluating the quality of the CH3NH3PbI3 perovskite structures is quite critical both to the design and fabrication of high-performance perovskite devices and to fundamental studies of the photophysics of the excitons. In particular, it is known that, under ambient conditions, CH3NH3PbI3 degrades producing some PbI2. We show here that low temperature Photoluminescence (PL) spectroscopy is a powerful tool to detect PbI2 traces in hybrid perovskite layers and single crystals. Because PL spectroscopy is a signal detection method on a black background, small PbI2 traces can be detected, when other methods currently used at room temperature fail. Our study highlights the extremely high stability of the single crystals compared to the thin layers and defects and grain boundaries are thought to play an important role in the degradation mechanism. PMID- 27399670 TI - Natural Bioactive Compounds: The Way Shown by Professor Maurizio Battino and His Group in an Italian Cutting-Edge Laboratory. AB - Maurizio Battino, Ph.D., Associate Professor of Biochemistry in the Department of Clinical Sciences, Faculty of Medicine, Universita Politecnica delle Marche (Italy), is the Director of the Centre for Health and Nutrition, Universidad Europea del Atlantico (Santander, Spain) and Director of Nutrition and Health projects and Master courses at FUNIBER on-line platform (Barcelona, Spain).[...]. PMID- 27399671 TI - Diet Quality and Cancer Outcomes in Adults: A Systematic Review of Epidemiological Studies. AB - Dietary patterns influence cancer risk. However, systematic reviews have not evaluated relationships between a priori defined diet quality scores and adult cancer risk and mortality. The aims of this systematic review are to (1) describe diet quality scores used in cohort or cross-sectional research examining cancer outcomes; and (2) describe associations between diet quality scores and cancer risk and mortality. The protocol was registered in Prospero, and a systematic search using six electronic databases was conducted through to December 2014. Records were assessed for inclusion by two independent reviewers, and quality was evaluated using a validated tool. Sixty-four studies met inclusion criteria from which 55 different diet quality scores were identified. Of the 35 studies investigating diet quality and cancer risk, 60% (n = 21) found a positive relationship. Results suggest no relationship between diet quality scores and overall cancer risk. Inverse associations were found for diet quality scores and risk of postmenopausal breast, colorectal, head, and neck cancer. No consistent relationships between diet quality scores and cancer mortality were found. Diet quality appears to be related to site-specific adult cancer risk. The relationship with cancer mortality is less conclusive, suggesting additional factors impact overall cancer survival. Development of a cancer-specific diet quality score for application in prospective epidemiology and in public health is warranted. PMID- 27399672 TI - Staphylococcal Superantigen-Like Protein 1 and 5 (SSL1 & SSL5) Limit Neutrophil Chemotaxis and Migration through MMP-Inhibition. AB - Matrix metalloproteinases (MMPs) are endopeptidases that degrade components of the extracellular matrix, but also modulate inflammation. During bacterial infections, MMPs are important in the recruitment and migration of inflammatory cells. Besides facilitating cell migration by degrading extracellular matrix components, they potentiate the action of several inflammatory molecules, including cytokines, chemokines, and antimicrobial peptides. Staphylococcus aureus secretes an arsenal of immune evasion molecules that interfere with immune cell functioning and hamper proper immune responses. An earlier study identified staphylococcal superantigen-like protein 5 (SSL5) as an MMP9 inhibitor. Since multiple MMPs are involved in neutrophil recruitment, we set up an in-depth search for additional MMP inhibitors by testing a panel of over 70 secreted staphylococcal proteins on the inhibition of the two main neutrophil MMPs: MMP8 (neutrophil collagenase) and MMP9 (neutrophil gelatinase B). We identified SSL1 and SSL5 as potent inhibitors of both neutrophil MMPs and show that they are actually broad range MMP inhibitors. SSL1 and SSL5 prevent MMP-induced cleavage and potentiation of IL-8 and inhibit the migration of neutrophils through collagen. Thus, through MMP-inhibition, SSL1 and SSL5 interfere with neutrophil activation, chemotaxis, and migration, all vital neutrophil functions in bacterial clearance. Studies on MMP-SSL interactions can have therapeutic potential and SSL based derivatives might prove useful in treatment of cancer and destructive inflammatory diseases. PMID- 27399674 TI - Bone Marrow Mesenchymal Stem Cells Expressing Baculovirus-Engineered Bone Morphogenetic Protein-7 Enhance Rabbit Posterolateral Fusion. AB - Previous studies have suggested that bone marrow-derived mesenchymal stem cells (BMDMSCs) genetically modified with baculoviral bone morphogenetic protein-2 (Bac BMP-2) vectors could achieve successful fusion in a femur defect model or in a spinal fusion model. In this study, BMDMSCs expressing BMP-7 (Bac-BMP-7-BMDMSCs) were generated. We hypothesized that Bac-BMP-7-BMDMSCs could secrete more BMP-7 than untransduced BMDMSCs in vitro and achieve spinal posterolateral fusion in a rabbit model. Eighteen rabbits underwent posterolateral fusion at L4-5. Group I (n = 6) was implanted with collagen-beta-tricalcium phosphate (TCP) hydroxyapatite (HA), Group II (n = 6) was implanted with collagen-beta-TCP-HA plus BMDMSCs, and Group III (n = 6) was implanted with collagen-beta-TCP-HA plus Bac-BMP-7-BMDMSCs. In vitro production of BMP-7 was quantified with an enzyme linked immunosorbent assay (ELISA). Spinal fusion was examined using computed tomography (CT), manual palpation, and histological analysis. ELISA demonstrated that Bac-BMP-7-BMDMSCs produced four-fold to five-fold more BMP-7 than did BMDMSCs. In the CT results, 6 fused segments were observed in Group I (50%, 6/12), 8 in Group II (67%, 8/12), and 12 in Group III (100%, 12/12). The fusion rate, determined by manual palpation, was 0% (0/6) in Group I, 0% (0/6) in Group II, and 83% (5/6) in Group III. Histology showed that Group III had more new bone and matured marrow formation. In conclusion, BMDMSCs genetically transduced with the Bac-BMP-7 vector could express more BMP-7 than untransduced BMDMSCs. These Bac-BMP-7-BMDMSCs on collagen-beta-TCP-HA scaffolds were able to induce successful spinal fusion in rabbits. PMID- 27399673 TI - Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions. AB - Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC. PMID- 27399675 TI - The Effect of Resveratrol and Quercetin Treatment on PPAR Mediated Uncoupling Protein (UCP-) 1, 2, and 3 Expression in Visceral White Adipose Tissue from Metabolic Syndrome Rats. AB - Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS). We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT) from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV) and quercetin (QRC). We found that UCP2 was the predominantly expressed isoform, UCP3 was present at very low levels, and UCP1 was undetectable. The treatment with RSV + QRC did not modify UCP3 levels; however, it significantly increased UCP2 mRNA in control and MetS rats in association with an increase in oleic and linoleic fatty acids. WAT from MetS rats showed a significantly increased expression of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma when compared to the control group. Furthermore, PPAR-alpha protein levels were increased by the highest dose of RSV + QRC in the control and MetS groups. PPAR gamma expression was only increased in the control group. We conclude that the RSV + QRC treatment leads to overexpression of UCP2, which is associated with an increase in MUFA and PUFA, which might increase PPAR-alpha expression. PMID- 27399676 TI - Protonation Sites, Tandem Mass Spectrometry and Computational Calculations of o Carbonyl Carbazolequinone Derivatives. AB - A series of a new type of tetracyclic carbazolequinones incorporating a carbonyl group at the ortho position relative to the quinone moiety was synthesized and analyzed by tandem electrospray ionization mass spectrometry (ESI/MS-MS), using Collision-Induced Dissociation (CID) to dissociate the protonated species. Theoretical parameters such as molecular electrostatic potential (MEP), local Fukui functions and local Parr function for electrophilic attack as well as proton affinity (PA) and gas phase basicity (GB), were used to explain the preferred protonation sites. Transition states of some main fragmentation routes were obtained and the energies calculated at density functional theory (DFT) B3LYP level were compared with the obtained by ab initio quadratic configuration interaction with single and double excitation (QCISD). The results are in accordance with the observed distribution of ions. The nature of the substituents in the aromatic ring has a notable impact on the fragmentation routes of the molecules. PMID- 27399677 TI - Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells. AB - 1alpha,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation inducer for acute myeloid leukemia (AML) cells. However, 1,25D3 doses required for differentiation of AML cells may cause lethal hypercalcemia in vivo. There is evidence that vitamin D2 is less toxic than vitamin D3 in animals. Here, we determined the differentiation effects of novel analogs of 1alpha,25 dihydroxyvitamin D2 (1,25D2), PRI-1916 and PRI-1917, in which the extended side chains of their previously reported precursors (PRI-1906 and PRI-1907, respectively) underwent further 24Z (24-cis) modification. Using four human AML cell lines representing different stages of myeloid maturation (KG-1a, HL60, U937, and MOLM-13), we found that the potency of PRI-1916 was slightly higher or equal to that of PRI-1906 while PRI-1917 was significantly less potent than PRI 1907. We also demonstrated that 1,25D2 was a less effective differentiation agent than 1,25D3 in these cell lines. Irrespective of their differentiation potency, all the vitamin D2 derivatives tested were less potent than 1,25D3 in transactivating the DR3-type vitamin D response elements. However, similar to 1,25D3, both 1,25D2 and its analogs could strongly cooperate with the plant polyphenol carnosic acid in inducing cell differentiation and inhibition of G1-S cell cycle transition. These results indicate that the 24Z modification has contrasting effects on the differentiation ability of PRI-1906 and PRI-1907 and that the addition of a plant polyphenol could result in a similar extent of cell differentiation induced by different vitamin D compounds. The enhanced antileukemic effects of the tested combinations may constitute the basis for the development of novel approaches for differentiation therapy of AML. PMID- 27399678 TI - The Systemic Profile of Soluble Immune Mediators in Patients with Myelodysplastic Syndromes. AB - INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure due to disturbed bone marrow maturation. MDS is associated with increased risk of transformation to acute myeloid leukemia (AML) and features of immunological dysregulation. MATERIALS AND METHODS: Serum levels of 47 soluble immune mediators were examined in samples derived from 49 MDS patients (35 low risk and 14 high-risk) and 23 healthy adults. Our patients represent an unselected population-based cohort. The mediators included cytokines, soluble adhesion proteins, matrix metalloproteases, and tissue inhibitors of proteases. Levels were determined using Luminex assays. Patients were classified as low- and high-risk based on the international prognostic scoring system (IPSS) score. RESULTS: When comparing the serum levels of single mediators the MDS patients showed a relatively wide variation range for several mediators compared with healthy adults, especially interleukin 6 (IL-6), IL-8/CXCL8, CCL3, and CCL4. The high-risk patients had lower levels of epidermal growth factor (EGF), cluster of differentiation 40 ligand (CD40L), CCL5, CCL11, CXCL5, matrix metalloproteinase 1 (MMP-1), MMP-9, and tissue inhibitor of metalloproteinases 2 (TIMP-2) compared with low-risk patients. Unsupervised hierarchical cluster analysis visualized marked serum mediator profile differences between MDS patients; based on this analysis three patient subsets could be identified. The healthy adults were also included in this analysis and, as expected, they formed their own separate cluster, except for one outlier. Both low- and high-risk patients showed considerable heterogeneity with regard to serum profile, and this heterogeneity seems stable over time (one year follow-up). Finally, very few mediators differed between low- and high-risk patients, but hierarchical clustering based both on all mediators, as well as five selected mediators (EGF, CCL11, TIMP-2, MMP-1, and MMP-9) identified subsets of patients with significantly increased frequency of high-risk disease (chi-square test p = 0.0158 and p = 0.0148). PMID- 27399679 TI - Evaluation of Housekeeping Genes for Quantitative Real-Time PCR Analysis of Bradysia odoriphaga (Diptera: Sciaridae). AB - The soil insect Bradysia odoriphaga (Diptera: Sciaridae) causes substantial damage to Chinese chive. Suitable reference genes in B. odoriphaga (Bradysia odoriphaga) have yet to be identified for normalizing target gene expression among samples by quantitative real-time PCR (qRT-PCR). This study was focused on identifying the expression stability of 12 candidate housekeeping genes in B. odoriphaga under various experiment conditions. The final stability ranking of 12 housekeeping genes was obtained with RefFinder, and the most suitable number of reference genes was analyzed by GeNorm. The results revealed that the most appropriate sets of internal controls were RPS15, RPL18, and RPS18 across developmental phases; RPS15, RPL28, and GAPDH across temperatures; RPS15 and RPL18 across pesticide treatments; RSP5, RPS18, and SDHA across photoperiods; ACTb, RPS18, and RPS15 across diets; RPS13 and RPL28 across populations; and RPS15, ACTb, and RPS18 across all samples. The use of the most suitable reference genes versus an arbitrarily selected reference gene resulted in significant differences in the analysis of a target gene expression. HSP23 in B. odoriphaga was found to be up-regulated under low temperatures. These results will contribute to the standardization of qRT-PCR and will also be valuable for further research on gene function in B. odoriphaga. PMID- 27399680 TI - Control of Appetite and Food Preference by NMDA Receptor and Its Co-Agonist d Serine. AB - Obesity causes a significant negative impact on health of human beings world wide. The main reason for weight gain, which eventually leads to obesity, is excessive ingestion of energy above the body's homeostatic needs. Therefore, the elucidation of detailed mechanisms for appetite control is necessary to prevent and treat obesity. N-methyl-d-aspartate (NMDA) receptor is a post-synaptic glutamate receptor and is important for excitatory neurotransmission. It is expressed throughout the nervous system, and is important for long-term potentiation. It requires both ligand (glutamate) and co-agonist (d-serine or glycine) for efficient opening of the channel to allow calcium influx. d-serine is contained in fermented foods and marine invertebrates, and brain d-serine level is maintained by synthesis in vivo and supply from food and gut microbiota. Although the NMDA receptor has been reported to take part in the central regulation of appetite, the role of d-serine had not been addressed. We recently reported that exogenous d-serine administration can suppress appetite and alter food preference. In this review, we will discuss how NMDA receptor and its co agonist d-seine participate in the control of appetite and food preference, and elaborate on how this system could possibly be manipulated to suppress obesity. PMID- 27399681 TI - Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase. AB - Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs), suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2). Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential. PMID- 27399682 TI - Endometriosis Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan. AB - This study was conducted to determine the risk of chronic kidney disease (CKD) among women with endometriosis in Taiwan. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan. A total of 27,973 women with a diagnosis of endometriosis and 27,973 multivariable-matched controls (1:1) from 2000 to 2010 were selected. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of CKD among women with endometriosis. The incidence rates (IR, per 10,000 person-years) of CKD among women with and without endometriosis were 4.64 and 7.01, respectively, with a significantly decreased risk of CKD (crude HR 0.65, 95% CI 0.53-0.81; adjusted HR 0.69, 95% CI 0.56-0.86) among women with endometriosis. The IR of CKD progressively increased with age, but the trend of lower CKD risk among women with endometriosis was consistent. However, the lower risk of CKD in women with endometriosis was no longer statistically significant after adjusting for menopausal status (adjusted HR 0.85, 95% CI 0.65-1.10). The results suggest that endometriosis is inversely associated with CKD, but this effect was mediated by menopause. The possible mechanism of this association is worthy of further evaluation. PMID- 27399683 TI - MicroRNA-146a-5p Negatively Regulates Pro-Inflammatory Cytokine Secretion and Cell Activation in Lipopolysaccharide Stimulated Human Hepatic Stellate Cells through Inhibition of Toll-Like Receptor 4 Signaling Pathways. AB - Lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway is demonstrated to be involved in the hepatic fibrosis. MicroRNA (miR)-146a-5p is a key regulator of the innate immune response. The functional significance of miR 146a-5p during the LPS/TLR4 mediated hepatic fibrosis process remains unclear. In this study, we found that TLR4 and alpha-smooth muscle actin (alpha-SMA) were up regulated and miR-146a-5p was down-regulated in human hepatic stellate cell (HSC) line LX2 after LPS stimulation. Overexpression of miR-146a-5p inhibited LPS induced pro-inflammatory cytokines secretion through down-regulating the expression levels of TLR-4, IL-1 receptor-associated kinase 1 (IRAK1), TNF receptor associated factor-6 (TRAF6) and phosphorylation of nuclear factor-kappa B (NF-kappaB). Knockdown of IRAK1 and TRAF6 also suppressed pro-inflammatory cytokine production by inhibiting NF-kappaB phosphorylation. In addition, miR 146a-5p mimic blocked LPS induced TRAF6 dependent c-Jun N-terminal kinase (JNK) and Smad2 activation as well as alpha-SMA production. Taken together, these results suggest that miR-146a-5p suppresses pro-inflammatory cytokine secretion and cell activation of HSC through inhibition of TLR4/NF-kappaB and TLR4/TRAF6/JNK pathway. PMID- 27399684 TI - Anti-Cancer Effect of Lambertianic Acid by Inhibiting the AR in LNCaP Cells. AB - Lambertianic acid (LA) is known to have anti-allergic and antibacterial effects. However, the anticancer activities and mechanism of action of LA have not been investigated. Therefore, the anticancer effects and mechanism of LA are investigated in this study. LA decreased not only AR protein levels, but also cellular and secretory levels of PSA. Furthermore, LA inhibited nuclear translocation of the AR induced by mibolerone. LA suppressed cell proliferation by inducing G1 arrest, downregulating CDK4/6 and cyclin D1 and activating p53 and its downstream molecules, p21 and p27. LA induced apoptosis and the expression of related proteins, including cleaved caspase-9 and -3, c-PARP and BAX, and inhibited BCl-2. The role of AR in LA-induced apoptosis was assessed by using siRNA. Collectively, these findings suggest that LA exerts the anticancer effect by inhibiting AR and is a valuable therapeutic agent in prostate cancer treatment. PMID- 27399685 TI - Molecular Dynamics Simulation Study of the Selectivity of a Silica Polymer for Ibuprofen. AB - In the past few years, the sol-gel polycondensation technique has been increasingly employed with great success as an alternative approach to the preparation of molecularly imprinted materials (MIMs). The main aim of this study was to study, through a series of molecular dynamics (MD) simulations, the selectivity of an imprinted silica xerogel towards a new template-the (+/-)-2-(P Isobutylphenyl) propionic acid (Ibuprofen, IBU). We have previously demonstrated the affinity of this silica xerogel toward a similar molecule. In the present study, we simulated the imprinting process occurring in a sol-gel mixture using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field, in order to evaluate the selectivity of this xerogel for a template molecule. In addition, for the first time, we have developed and verified a new parameterisation for the Ibuprofen((r)) based on the OPLS-AA framework. To evaluate the selectivity of the polymer, we have employed both the radial distribution functions, interaction energies and cluster analyses. PMID- 27399686 TI - Comparative Analysis of the Chloroplast Genomic Information of Cunninghamia lanceolata (Lamb.) Hook with Sibling Species from the Genera Cryptomeria D. Don, Taiwania Hayata, and Calocedrus Kurz. AB - Chinese fir (Cunninghamia lanceolata (Lamb.) Hook) is an important coniferous tree species for timber production, which accounts for ~40% of log supply from plantations in southern China. Chloroplast genetic engineering is an exciting field to engineer several valuable tree traits. In this study, we revisited the published complete Chinese fir (NC_021437) and four other coniferous species chloroplast genome sequence in Taxodiaceae. Comparison of their chloroplast genomes revealed three unique inversions found in the downstream of the gene clusters and evolutionary divergence were found, although overall the chloroplast genomic structure of the Cupressaceae linage was conserved. We also investigated the phylogenetic position of Chinese fir among conifers by examining gene functions, selection forces, substitution rates, and the full chloroplast genome sequence. Consistent with previous molecular systematics analysis, the results provided a well-supported phylogeny framework for the Cupressaceae that strongly confirms the "basal" position of Cunninghamia lanceolata. The structure of the Cunninghamia lanceolata chloroplast genome showed a partial lack of one IR copy, rearrangements clearly occurred and slight evolutionary divergence appeared among the cp genome of C. lanceolata, Taiwania cryptomerioides, Taiwania flousiana, Calocedrus formosana and Cryptomeria japonica. The information from sequence divergence and length variation of genes could be further considered for bioengineering research. PMID- 27399687 TI - Dual-Labeled Near-Infrared/(99m)Tc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells. AB - We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells and achieve efficient target imaging of HER2 expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2 expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner. PMID- 27399688 TI - Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer. AB - The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% +/- 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)3(H2O)3]+ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 degrees C with a relatively low lipophilicity (logD = 2.15 +/- 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 +/- 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% +/- 0.17% and 7.87% +/- 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation. PMID- 27399689 TI - Compound K Attenuates the Development of Atherosclerosis in ApoE(-/-) Mice via LXRalpha Activation. AB - BACKGROUND: Atherosclerosis is a fundamental pathological process responded to some serious cardiovascular events. Although the cholesterol-lowering drugs are widely prescribed for atherosclerosis therapy, it is still the leading cause of death in the developed world. Here we measured the effects of compound K in atherosclerosis formation and investigated the probably mechanisms of the anti antherosclerosis roles of compound K. METHODS: We treated the atherosclerotic model animals (apoE(-/-) mice on western diet) with compound K and measured the size of atherosclerotic lesions, inflammatory cytokine levels and serum lipid profile. Peritoneal macrophages were collected in vitro for the foam cell and inflammasome experiments. RESULTS: Our results show that treatment with compound K dose-dependently attenuates the formation of atherosclerotic plaques by 55% through activation of reverse cholesterol transport pathway, reduction of systemic inflammatory cytokines and inhibition of local inflammasome activity. Compound K increases the cholesterol efflux of macrophage-derived foam cells, and reduces the inflammasome activity in cholesterol crystal stimulated macrophages. The activation of LXRalpha may contribute to the athero-protective effects of compound K. CONCLUSION: These observations provide evidence for an athero protective effect of compound K via LXRalpha activation, and support its further evaluation as a potential effective modulator for the prevention and treatment of atherosclerosis. PMID- 27399690 TI - Liver Fat Measured by MR Spectroscopy: Estimate of Imprecision and Relationship with Serum Glycerol, Caeruloplasmin and Non-Esterified Fatty Acids. AB - Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042), homeostasis model assessment (HOMA)-B% (T = 0.48, p = 0.042), and body mass index (BMI) (T = 0.59, p = 0.012); and inversely related to HOMA-S% (T = -0.48, p = 0.042), serum glycerol (T = -0.59, p = 0.014), and serum caeruloplasmin (T = 0.055, p = 0.047). Our estimate of total variability in liver fat content (14.8%) is nearly twice that of the reported procedural variability (8.5%). We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA), suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis. PMID- 27399691 TI - MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia. AB - Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC. PMID- 27399692 TI - Chemical Structure-Biological Activity Models for Pharmacophores' 3D Interactions. AB - Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2 guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners' (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions. PMID- 27399693 TI - miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells. AB - Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non coding RNAs with lengths of 18-25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1), miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated beta-galactosidase positive cells, the expression of p16(INK4a) and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1. PMID- 27399694 TI - The Prognostic and Predictive Role of Epidermal Growth Factor Receptor in Surgical Resected Pancreatic Cancer. AB - The data regarding the prognostic significance of EGFR (epidermal growth factor receptor) expression and adjuvant therapy in patients with resected pancreatic cancer are insufficient. We retrospectively investigated EGFR status in 357 resected PDAC (pancreatic duct adenocarcinoma) patients using tissue immunohistochemistry and validated the possible role of EGFR expression in predicting prognosis. The analysis was based on excluding the multiple confounding parameters. A negative association was found between overall EGFR status and postoperative survival (p = 0.986). Remarkably, adjuvant chemotherapy and radiotherapy were significantly associated with favorable postoperative survival, which prolonged median overall survival (OS) for 5.8 and 10.2 months (p = 0.009 and p = 0.006, respectively). Kaplan-Meier analysis showed that adjuvant chemotherapy correlated with an obvious survival benefit in the EGFR-positive subgroup rather than in the EGFR-negative subgroup. In the subgroup analyses, chemotherapy was highly associated with increased postoperative survival in the EGFR-negative subgroup (p = 0.002), and radiotherapy had a significant survival benefit in the EGFR-positive subgroup (p = 0.029). This study demonstrated that EGFR expression is not correlated with outcome in resected pancreatic cancer patients. Adjuvant chemotherapy and radiotherapy were significantly associated with improved survival in contrary EGFR expressing subgroup. Further studies of EGFR as a potential target for pancreatic cancer treatment are warranted. PMID- 27399695 TI - Piriformospora indica Stimulates Root Metabolism of Arabidopsis thaliana. AB - Piriformospora indica is a root-colonizing fungus, which interacts with a variety of plants including Arabidopsis thaliana. This interaction has been considered as mutualistic leading to growth promotion of the host. So far, only indolic glucosinolates and phytohormones have been identified as key players. In a comprehensive non-targeted metabolite profiling study, we analyzed Arabidopsis thaliana's roots, root exudates, and leaves of inoculated and non-inoculated plants by ultra performance liquid chromatography/electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC/(ESI)-QTOFMS) and gas chromatography/electron ionization quadrupole mass spectrometry (GC/EI-QMS), and identified further biomarkers. Among them, the concentration of nucleosides, dipeptides, oligolignols, and glucosinolate degradation products was affected in the exudates. In the root profiles, nearly all metabolite levels increased upon co-cultivation, like carbohydrates, organic acids, amino acids, glucosinolates, oligolignols, and flavonoids. In the leaf profiles, we detected by far less significant changes. We only observed an increased concentration of organic acids, carbohydrates, ascorbate, glucosinolates and hydroxycinnamic acids, and a decreased concentration of nitrogen-rich amino acids in inoculated plants. These findings contribute to the understanding of symbiotic interactions between plant roots and fungi of the order of Sebacinales and are a valid source for follow-up mechanistic studies, because these symbioses are particular and clearly different from interactions of roots with mycorrhizal fungi or dark septate endophytes. PMID- 27399696 TI - A Novel Wearable Sensor-Based Human Activity Recognition Approach Using Artificial Hydrocarbon Networks. AB - Human activity recognition has gained more interest in several research communities given that understanding user activities and behavior helps to deliver proactive and personalized services. There are many examples of health systems improved by human activity recognition. Nevertheless, the human activity recognition classification process is not an easy task. Different types of noise in wearable sensors data frequently hamper the human activity recognition classification process. In order to develop a successful activity recognition system, it is necessary to use stable and robust machine learning techniques capable of dealing with noisy data. In this paper, we presented the artificial hydrocarbon networks (AHN) technique to the human activity recognition community. Our artificial hydrocarbon networks novel approach is suitable for physical activity recognition, noise tolerance of corrupted data sensors and robust in terms of different issues on data sensors. We proved that the AHN classifier is very competitive for physical activity recognition and is very robust in comparison with other well-known machine learning methods. PMID- 27399697 TI - Correction: Alvarado, M., et al. Towards the Development of a Low Cost Airborne Sensing System to Monitor Dust Particles after Blasting at Open-Pit Mine Sites. Sensors 2015, 15, 19667-19687. AB - The author wishes to change Figure 1 and Figure 3 from his paper published in Sensors [1], doi:10.3390/s150819667, website: http://www.mdpi.com/1424 8220/15/8/19667 for Figures 1 and 2 presented in this 'Correction'.[...]. PMID- 27399698 TI - Correction: Vazquez-Arellano, M., et al. 3-D Imaging Systems for Agricultural Applications-A Review. Sensors 2016, 16, 618. AB - The authors wish to make the following corrections to Table 1 of the title paper [1]: the working environment of the PlantEye platform should be changed from "Greenhouse" to "Open field, Greenhouse" and the shadowing device of the Scanalyzer platform should be changed from "'?" to "x". [...]. PMID- 27399699 TI - A Reliable TTP-Based Infrastructure with Low Sensor Resource Consumption for the Smart Home Multi-Platform. AB - With the ICT technology making great progress in the smart home environment, the ubiquitous environment is rapidly emerging all over the world, but problems are also increasing proportionally to the rapid growth of the smart home market such as multiplatform heterogeneity and new security threats. In addition, the smart home sensors have so low computing resources that they cannot process complicated computation tasks, which is required to create a proper security environment. A service provider also faces overhead in processing data from a rapidly increasing number of sensors. This paper aimed to propose a scheme to build infrastructure in which communication entities can securely authenticate and design security channel with physically unclonable PUFs and the TTP that smart home communication entities can rely on. In addition, we analyze and evaluate the proposed scheme for security and performance and prove that it can build secure channels with low resources. Finally, we expect that the proposed scheme can be helpful for secure communication with low resources in future smart home multiplatforms. PMID- 27399700 TI - Policy 2.0 Platform for Mobile Sensing and Incentivized Targeted Shifts in Mobility Behavior. AB - Sustainable mobility and smart mobility management play important roles in achieving smart cities' goals. In this context we investigate the role of smartphones as mobility behavior sensors and evaluate the responsivity of different attitudinal profiles towards personalized route suggestion incentives delivered via mobile phones. The empirical results are based on mobile sensed data collected from more than 3400 people's real life over a period of six months. The findings show which user profiles are most likely to accept such incentives and how likely they are to result in more sustainable mode choices. In addition we provide insights into tendencies towards accepting more sustainable route options for different trip purposes and illustrate smart city platform potential (for collection of mobility behavior data and delivery of incentives) as a tool for development of personalized mobility management campaigns and policies. PMID- 27399701 TI - Autonomous Quality Control of Joint Orientation Measured with Inertial Sensors. AB - Clinical mobility assessment is traditionally performed in laboratories using complex and expensive equipment. The low accessibility to such equipment, combined with the emerging trend to assess mobility in a free-living environment, creates a need for body-worn sensors (e.g., inertial measurement units-IMUs) that are capable of measuring the complexity in motor performance using meaningful measurements, such as joint orientation. However, accuracy of joint orientation estimates using IMUs may be affected by environment, the joint tracked, type of motion performed and velocity. This study investigates a quality control (QC) process to assess the quality of orientation data based on features extracted from the raw inertial sensors' signals. Joint orientation (trunk, hip, knee, ankle) of twenty participants was acquired by an optical motion capture system and IMUs during a variety of tasks (sit, sit-to-stand transition, walking, turning) performed under varying conditions (speed, environment). An artificial neural network was used to classify good and bad sequences of joint orientation with a sensitivity and a specificity above 83%. This study confirms the possibility to perform QC on IMU joint orientation data based on raw signal features. This innovative QC approach may be of particular interest in a big data context, such as for remote-monitoring of patients' mobility. PMID- 27399702 TI - Design of Flow Systems for Improved Networking and Reduced Noise in Biomolecular Signal Processing in Biocomputing and Biosensing Applications. AB - We consider flow systems that have been utilized for small-scale biomolecular computing and digital signal processing in binary-operating biosensors. Signal measurement is optimized by designing a flow-reversal cuvette and analyzing the experimental data to theoretically extract the pulse shape, as well as reveal the level of noise it possesses. Noise reduction is then carried out numerically. We conclude that this can be accomplished physically via the addition of properly designed well-mixing flow-reversal cell(s) as an integral part of the flow system. This approach should enable improved networking capabilities and potentially not only digital but analog signal-processing in such systems. Possible applications in complex biocomputing networks and various sense-and-act systems are discussed. PMID- 27399703 TI - Developing a Penetrometer-Based Mapping System for Visualizing Silage Bulk Density from the Bunker Silo Face. AB - For silage production, high bulk density (BD) is critical to minimize aerobic deterioration facilitated by oxygen intrusion. To precisely assess packing quality for bunker silos, there is a desire to visualize the BD distribution within the silage. In this study, a penetrometer-based mapping system was developed. The data processing included filtering of the penetration friction component (PFC) out of the penetration resistance (PR), transfer of the corrected penetration resistance (PRc) to BD, incorporation of Kriged interpolation for data expansion and map generation. The experiment was conducted in a maize bunker silo (width: 8 m, middle height: 3 m). The BD distributions near the bunker silo face were represented using two map groups, one related to horizontal- and the other to vertical-density distribution patterns. We also presented a comparison between the map-based BD results and core sampling data. Agreement between the two measurement approaches (RMSE = 19.175 kg.m(-3)) demonstrates that the developed penetrometer mapping system may be beneficial for rapid assessment of aerobic deterioration potential in bunker silos. PMID- 27399704 TI - Filtering Based Adaptive Visual Odometry Sensor Framework Robust to Blurred Images. AB - Visual odometry (VO) estimation from blurred image is a challenging problem in practical robot applications, and the blurred images will severely reduce the estimation accuracy of the VO. In this paper, we address the problem of visual odometry estimation from blurred images, and present an adaptive visual odometry estimation framework robust to blurred images. Our approach employs an objective measure of images, named small image gradient distribution (SIGD), to evaluate the blurring degree of the image, then an adaptive blurred image classification algorithm is proposed to recognize the blurred images, finally we propose an anti blurred key-frame selection algorithm to enable the VO robust to blurred images. We also carried out varied comparable experiments to evaluate the performance of the VO algorithms with our anti-blur framework under varied blurred images, and the experimental results show that our approach can achieve superior performance comparing to the state-of-the-art methods under the condition with blurred images while not increasing too much computation cost to the original VO algorithms. PMID- 27399705 TI - Flexible Piezoelectric Energy Harvesting from Mouse Click Motions. AB - In this paper, we study energy harvesting from the mouse click motions of a robot finger and a human index finger using a piezoelectric material. The feasibility of energy harvesting from mouse click motions is experimentally and theoretically assessed. The fingers wear a glove with a pocket for including the piezoelectric material. We model the energy harvesting system through the inverse kinematic framework of parallel joints in a finger and the electromechanical coupling equations of the piezoelectric material. The model is validated through energy harvesting experiments in the robot and human fingers with the systematically varying load resistance. We find that energy harvesting is maximized at the matched load resistance to the impedance of the piezoelectric material, and the harvested energy level is tens of nJ. PMID- 27399706 TI - Microwave Imaging under Oblique Illumination. AB - Microwave imaging based on inverse scattering problem has been attracting many interests in the microwave society. Among some major technical challenges, the ill-posed, multi-dimensional inversion algorithm and the complicated measurement setup are critical ones that prevent it from practical applications. In this paper, we experimentally investigate the performance of the subspace-based optimization method (SOM) for two-dimensional objects when it was applied to a setup designed for oblique incidence. Analytical, simulation, and experimental results show that, for 2D objects, neglecting the cross-polarization scattering will not cause a notable loss of information. Our method can be potentially used in practical imaging applications for 2D-like objects, such as human limbs. PMID- 27399707 TI - An MEF-Based Localization Algorithm against Outliers in Wireless Sensor Networks. AB - Precise localization has attracted considerable interest in Wireless Sensor Networks (WSNs) localization systems. Due to the internal or external disturbance, the existence of the outliers, including both the distance outliers and the anchor outliers, severely decreases the localization accuracy. In order to eliminate both kinds of outliers simultaneously, an outlier detection method is proposed based on the maximum entropy principle and fuzzy set theory. Since not all the outliers can be detected in the detection process, the Maximum Entropy Function (MEF) method is utilized to tolerate the errors and calculate the optimal estimated locations of unknown nodes. Simulation results demonstrate that the proposed localization method remains stable while the outliers vary. Moreover, the localization accuracy is highly improved by wisely rejecting outliers. PMID- 27399709 TI - Rule-Based vs. Behavior-Based Self-Deployment for Mobile Wireless Sensor Networks. AB - In mobile wireless sensor networks (MWSN), nodes are allowed to move autonomously for deployment. This process is meant: (i) to achieve good coverage; and (ii) to distribute the communication load as homogeneously as possible. Rather than optimizing deployment, reactive algorithms are based on a set of rules or behaviors, so nodes can determine when to move. This paper presents an experimental evaluation of both reactive deployment approaches: rule-based and behavior-based ones. Specifically, we compare a backbone dispersion algorithm with a social potential fields algorithm. Most tests are done under simulation for a large number of nodes in environments with and without obstacles. Results are validated using a small robot network in the real world. Our results show that behavior-based deployment tends to provide better coverage and communication balance, especially for a large number of nodes in areas with obstacles. PMID- 27399708 TI - Node Detection and Internode Length Estimation of Tomato Seedlings Based on Image Analysis and Machine Learning. AB - Seedling vigor in tomatoes determines the quality and growth of fruits and total plant productivity. It is well known that the salient effects of environmental stresses appear on the internode length; the length between adjoining main stem node (henceforth called node). In this study, we develop a method for internode length estimation using image processing technology. The proposed method consists of three steps: node detection, node order estimation, and internode length estimation. This method has two main advantages: (i) as it uses machine learning approaches for node detection, it does not require adjustment of threshold values even though seedlings are imaged under varying timings and lighting conditions with complex backgrounds; and (ii) as it uses affinity propagation for node order estimation, it can be applied to seedlings with different numbers of nodes without prior provision of the node number as a parameter. Our node detection results show that the proposed method can detect 72% of the 358 nodes in time series imaging of three seedlings (recall = 0.72, precision = 0.78). In particular, the application of a general object recognition approach, Bag of Visual Words (BoVWs), enabled the elimination of many false positives on leaves occurring in the image segmentation based on pixel color, significantly improving the precision. The internode length estimation results had a relative error of below 15.4%. These results demonstrate that our method has the ability to evaluate the vigor of tomato seedlings quickly and accurately. PMID- 27399710 TI - A Cyber-Physical System for Girder Hoisting Monitoring Based on Smartphones. AB - Offshore design and construction is much more difficult than land-based design and construction, particularly due to hoisting operations. Real-time monitoring of the orientation and movement of a hoisted structure is thus required for operators' safety. In recent years, rapid development of the smart-phone commercial market has offered the possibility that everyone can carry a mini personal computer that is integrated with sensors, an operating system and communication system that can act as an effective aid for cyber-physical systems (CPS) research. In this paper, a CPS for hoisting monitoring using smartphones was proposed, including a phone collector, a controller and a server. This system uses smartphones equipped with internal sensors to obtain girder movement information, which will be uploaded to a server, then returned to controller users. An alarming system will be provided on the controller phone once the returned data exceeds a threshold. The proposed monitoring system is used to monitor the movement and orientation of a girder during hoisting on a cross-sea bridge in real time. The results show the convenience and feasibility of the proposed system. PMID- 27399711 TI - A Framework for the Development of Context-Adaptable User Interfaces for Ubiquitous Computing Systems. AB - This paper addresses the problem of developing user interfaces for Ubiquitous Computing (UC) and Ambient Intelligence (AmI) systems. These kind of systems are expected to provide a natural user experience, considering interaction modalities adapted to the user abilities and preferences and using whatever interaction devices are present in the environment. These interaction devices are not necessarily known at design time. The task is quite complicated due to the variety of devices and technologies, and the diversity of scenarios, and it usually burdens the developer with the need to create many different UIs in order to consider the foreseeable user-environment combinations. Here, we propose an UI abstraction framework for UC and AmI systems that effectively improves the portability of those systems between different environments and for different users. It allows developers to design and implement a single UI capable of being deployed with different devices and modalities regardless the physical location. PMID- 27399712 TI - Multiplexed Simultaneous High Sensitivity Sensors with High-Order Mode Based on the Integration of Photonic Crystal 1 * 3 Beam Splitter and Three Different Single-Slot PCNCs. AB - We simulated an efficient method for the sensor array of high-sensitivity single slot photonic crystal nanobeam cavities (PCNCs) on a silicon platform. With the combination of a well-designed photonic crystal waveguide (PhCW) filter and an elaborate single-slot PCNC, a specific high-order resonant mode was filtered for sensing. A 1 * 3 beam splitter carefully established was implemented to split channels and integrate three sensors to realize microarrays. By applying the three-dimensional finite-difference-time-domain (3D-FDTD) method, the sensitivities calculated were S1 = 492 nm/RIU, S2 = 244 nm/RIU, and S3 = 552 nm/RIU, respectively. To the best of our knowledge, this is the first multiplexing design in which each sensor cite features such a high sensitivity simultaneously. PMID- 27399713 TI - Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non Restrained, Non-Sedated Laboratory Mice. AB - Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown. PMID- 27399714 TI - Automatic Censoring CFAR Detector Based on Ordered Data Difference for Low-Flying Helicopter Safety. AB - Being equipped with a millimeter-wave radar allows a low-flying helicopter to sense the surroundings in real time, which significantly increases its safety. However, nonhomogeneous clutter environments, such as a multiple target situation and a clutter edge environment, can dramatically affect the radar signal detection performance. In order to improve the radar signal detection performance in nonhomogeneous clutter environments, this paper proposes a new automatic censored cell averaging CFAR detector. The proposed CFAR detector does not require any prior information about the background environment and uses the hypothesis test of the first-order difference (FOD) result of ordered data to reject the unwanted samples in the reference window. After censoring the unwanted ranked cells, the remaining samples are combined to form an estimate of the background power level, thus getting better radar signal detection performance. The simulation results show that the FOD-CFAR detector provides low loss CFAR performance in a homogeneous environment and also performs robustly in nonhomogeneous environments. Furthermore, the measured results of a low-flying helicopter validate the basic performance of the proposed method. PMID- 27399715 TI - First Eigenmode Transmission by High Efficient CSI Estimation for Multiuser Massive MIMO Using Millimeter Wave Bands. AB - Drastic improvements in transmission rate and system capacity are required towards 5th generation mobile communications (5G). One promising approach, utilizing the millimeter wave band for its rich spectrum resources, suffers area coverage shortfalls due to its large propagation loss. Fortunately, massive multiple-input multiple-output (MIMO) can offset this shortfall as well as offer high order spatial multiplexing gain. Multiuser MIMO is also effective in further enhancing system capacity by multiplexing spatially de-correlated users. However, the transmission performance of multiuser MIMO is strongly degraded by channel time variation, which causes inter-user interference since null steering must be performed at the transmitter. This paper first addresses the effectiveness of multiuser massive MIMO transmission that exploits the first eigenmode for each user. In Line-of-Sight (LoS) dominant channel environments, the first eigenmode is chiefly formed by the LoS component, which is highly correlated with user movement. Therefore, the first eigenmode provided by a large antenna array can improve the robustness against the channel time variation. In addition, we propose a simplified beamforming scheme based on high efficient channel state information (CSI) estimation that extracts the LoS component. We also show that this approximate beamforming can achieve throughput performance comparable to that of the rigorous first eigenmode transmission. Our proposed multiuser massive MIMO scheme can open the door for practical millimeter wave communication with enhanced system capacity. PMID- 27399716 TI - Design and Analysis of a New Hair Sensor for Multi-Physical Signal Measurement. AB - A new hair sensor for multi-physical signal measurements, including acceleration, angular velocity and air flow, is presented in this paper. The entire structure consists of a hair post, a torsional frame and a resonant signal transducer. The hair post is utilized to sense and deliver the physical signals of the acceleration and the air flow rate. The physical signals are converted into frequency signals by the resonant transducer. The structure is optimized through finite element analysis. The simulation results demonstrate that the hair sensor has a frequency of 240 Hz in the first mode for the acceleration or the air flow sense, 3115 Hz in the third and fourth modes for the resonant conversion, and 3467 Hz in the fifth and sixth modes for the angular velocity transformation, respectively. All the above frequencies present in a reasonable modal distribution and are separated from interference modes. The input-output analysis of the new hair sensor demonstrates that the scale factor of the acceleration is 12.35 Hz/g, the scale factor of the angular velocity is 0.404 nm/deg/s and the sensitivity of the air flow is 1.075 Hz/(m/s)2, which verifies the multifunction sensitive characteristics of the hair sensor. Besides, the structural optimization of the hair post is used to improve the sensitivity of the air flow rate and the acceleration. The analysis results illustrate that the hollow circular hair post can increase the sensitivity of the air flow and the II-shape hair post can increase the sensitivity of the acceleration. Moreover, the thermal analysis confirms the scheme of the frequency difference for the resonant transducer can prominently eliminate the temperature influences on the measurement accuracy. The air flow analysis indicates that the surface area increase of hair post is significantly beneficial for the efficiency improvement of the signal transmission. In summary, the structure of the new hair sensor is proved to be feasible by comprehensive simulation and analysis. PMID- 27399717 TI - Closed-Loop Lifecycle Management of Service and Product in the Internet of Things: Semantic Framework for Knowledge Integration. AB - This paper describes our conceptual framework of closed-loop lifecycle information sharing for product-service in the Internet of Things (IoT). The framework is based on the ontology model of product-service and a type of IoT message standard, Open Messaging Interface (O-MI) and Open Data Format (O-DF), which ensures data communication. (1) BACKGROUND: Based on an existing product lifecycle management (PLM) methodology, we enhanced the ontology model for the purpose of integrating efficiently the product-service ontology model that was newly developed; (2) METHODS: The IoT message transfer layer is vertically integrated into a semantic knowledge framework inside which a Semantic Info-Node Agent (SINA) uses the message format as a common protocol of product-service lifecycle data transfer; (3) RESULTS: The product-service ontology model facilitates information retrieval and knowledge extraction during the product lifecycle, while making more information available for the sake of service business creation. The vertical integration of IoT message transfer, encompassing all semantic layers, helps achieve a more flexible and modular approach to knowledge sharing in an IoT environment; (4) Contribution: A semantic data annotation applied to IoT can contribute to enhancing collected data types, which entails a richer knowledge extraction. The ontology-based PLM model enables as well the horizontal integration of heterogeneous PLM data while breaking traditional vertical information silos; (5) CONCLUSION: The framework was applied to a fictive case study with an electric car service for the purpose of demonstration. For the purpose of demonstrating the feasibility of the approach, the semantic model is implemented in Sesame APIs, which play the role of an Internet-connected Resource Description Framework (RDF) database. PMID- 27399718 TI - Portable System for Monitoring the Microclimate in the Footwear-Foot Interface. AB - A new, continuously-monitoring portable device that monitors the diabetic foot has shown to help in reduction of diabetic foot complications. Persons affected by diabetic foot have shown to be particularly sensitive in the plantar surface; this sensitivity coupled with certain ambient conditions may cause dry skin. This dry skin leads to the formation of fissures that may eventually result in a foot ulceration and subsequent hospitalization. This new device monitors the micro climate temperature and humidity areas between the insole and sole of the footwear. The monitoring system consists of an array of ten sensors that take readings of relative humidity within the range of 100% +/- 2% and temperature within the range of -40 degrees C to 123.8 +/- 0.3 degrees C. Continuous data is collected using embedded C software and the recorded data is processed in Matlab. This allows for the display of data; the implementation of the iterative Gauss-Newton algorithm method was used to display an exponential response curve. Therefore, the aim of our system is to obtain feedback data and provide the critical information to various footwear manufacturers. The footwear manufactures will utilize this critical information to design and manufacture diabetic footwear that reduce the risk of ulcers in diabetic feet. PMID- 27399719 TI - A Novel Strategy to Eliminate the Influence of Water Adsorption on Quartz Surfaces on Piezoelectric Dynamometers. AB - Piezoelectric dynamometers are out of use in high humidity. Experimental results showed that piezoelectric coefficients measured by the force-induced charges method initially fluctuated in a small range and then was unstable, and they could not be measured at high relative humidity (RH). The traditional shielding method-insulation paste was not quiet convenient, and it even added the weight of piezoelectric dynamometers. In this paper, a novel strategy that eliminates the influence of water adsorption with quartz surfaces on piezoelectric dynamometers was proposed. First, a water-quartz model was developed to analyze the origin of the RH effect. In the model, water vapor, which was adsorbed by the quartz sheet side surface, was considered. Second, equivalent sheet resistor of the side surface was researched, while the relationship of the three R's (Roughness, RH, and Resistor) was respectively discussed based on the adsorption mechanism. Finally, fluorination technology was skillfully adapted to each surface of quartz sheets to shield the water vapor. The experiment verified the fluorination strategy and made piezoelectric dynamometers work in high humidity up to 90%RH successfully. The results showed that the presented model above was reasonable. In addition, these observations also drew some useful insights to change the structure of piezoelectric dynamometers and improve the properties. PMID- 27399720 TI - Hyperspectral Image-Based Night-Time Vehicle Light Detection Using Spectral Normalization and Distance Mapper for Intelligent Headlight Control. AB - This paper proposes a vehicle light detection method using a hyperspectral camera instead of a Charge-Coupled Device (CCD) or Complementary metal-Oxide Semiconductor (CMOS) camera for adaptive car headlamp control. To apply Intelligent Headlight Control (IHC), the vehicle headlights need to be detected. Headlights are comprised from a variety of lighting sources, such as Light Emitting Diodes (LEDs), High-intensity discharge (HID), and halogen lamps. In addition, rear lamps are made of LED and halogen lamp. This paper refers to the recent research in IHC. Some problems exist in the detection of headlights, such as erroneous detection of street lights or sign lights and the reflection plate of ego-car from CCD or CMOS images. To solve these problems, this study uses hyperspectral images because they have hundreds of bands and provide more information than a CCD or CMOS camera. Recent methods to detect headlights used the Spectral Angle Mapper (SAM), Spectral Correlation Mapper (SCM), and Euclidean Distance Mapper (EDM). The experimental results highlight the feasibility of the proposed method in three types of lights (LED, HID, and halogen). PMID- 27399721 TI - Tightly Coupled Integration of GPS Ambiguity Fixed Precise Point Positioning and MEMS-INS through a Troposphere-Constrained Adaptive Kalman Filter. AB - Precise Point Positioning (PPP) makes use of the undifferenced pseudorange and carrier phase measurements with ionospheric-free (IF) combinations to achieve centimeter-level positioning accuracy. Conventionally, the IF ambiguities are estimated as float values. To improve the PPP positioning accuracy and shorten the convergence time, the integer phase clock model with between-satellites single-difference (BSSD) operation is used to recover the integer property. However, the continuity and availability of stand-alone PPP is largely restricted by the observation environment. The positioning performance will be significantly degraded when GPS operates under challenging environments, if less than five satellites are present. A commonly used approach is integrating a low cost inertial sensor to improve the positioning performance and robustness. In this study, a tightly coupled (TC) algorithm is implemented by integrating PPP with inertial navigation system (INS) using an Extended Kalman filter (EKF). The navigation states, inertial sensor errors and GPS error states are estimated together. The troposphere constrained approach, which utilizes external tropospheric delay as virtual observation, is applied to further improve the ambiguity-fixed height positioning accuracy, and an improved adaptive filtering strategy is implemented to improve the covariance modelling considering the realistic noise effect. A field vehicular test with a geodetic GPS receiver and a low cost inertial sensor was conducted to validate the improvement on positioning performance with the proposed approach. The results show that the positioning accuracy has been improved with inertial aiding. Centimeter-level positioning accuracy is achievable during the test, and the PPP/INS TC integration achieves a fast re-convergence after signal outages. For troposphere constrained solutions, a significant improvement for the height component has been obtained. The overall positioning accuracies of the height component are improved by 30.36%, 16.95% and 24.07% for three different convergence times, i.e., 60, 50 and 30 min, respectively. It shows that the ambiguity-fixed horizontal positioning accuracy has been significantly improved. When compared with the conventional PPP solution, it can be seen that position accuracies are improved by 19.51%, 61.11% and 23.53% for the north, east and height components, respectively, after one hour convergence through the troposphere constraint fixed PPP/INS with adaptive covariance model. PMID- 27399722 TI - T-L Plane Abstraction-Based Energy-Efficient Real-Time Scheduling for Multi-Core Wireless Sensors. AB - Energy efficiency is considered as a critical requirement for wireless sensor networks. As more wireless sensor nodes are equipped with multi-cores, there are emerging needs for energy-efficient real-time scheduling algorithms. The T-L plane-based scheme is known to be an optimal global scheduling technique for periodic real-time tasks on multi-cores. Unfortunately, there has been a scarcity of studies on extending T-L plane-based scheduling algorithms to exploit energy saving techniques. In this paper, we propose a new T-L plane-based algorithm enabling energy-efficient real-time scheduling on multi-core sensor nodes with dynamic power management (DPM). Our approach addresses the overhead of processor mode transitions and reduces fragmentations of the idle time, which are inherent in T-L plane-based algorithms. Our experimental results show the effectiveness of the proposed algorithm compared to other energy-aware scheduling methods on T-L plane abstraction. PMID- 27399723 TI - Multiple Functions of the New Cytokine-Based Antimicrobial Peptide Thymic Stromal Lymphopoietin (TSLP). AB - Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal alpha-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes. PMID- 27399724 TI - Polylactic Acid-Lemongrass Essential Oil Nanocapsules with Antimicrobial Properties. AB - Polylactic acid was combined with lemongrass essential oil (EO) to produce functional nanocapsules (NCs). The obtained polylactic acid nanoparticles showed antimicrobial activity both with and without the presence of lemongrass oil; however, the presence of EO improved the activity of the NCs. The presence of lemongrass assisted the formation of well-separated NCs and also provided enhanced antimicrobial properties, since lemongrass is known for its antimicrobial character. Fluorescence microscopy was used to optically observe the nanoparticles and NCs and revealed the attachment of lemongrass oil with the polylactic acid NCs. Dynamic light scattering was used to determine their size. UV absorption was used to determine the exact amount of lemongrass oil found in the polylactic acid-lemongrass oil NCs, which was important for understanding the minimum inhibitory concentration for the antimicrobial experiments. A series of clinically important microbial species were used in the study and the obtained NCs proved to have very good antimicrobial properties against all tested strains. Such NCs can be used for the design of ecological strategies, based on natural alternatives, which may be efficient against severe infections, including those that involve resistant pathogens and biofilms or those with difficult to reach localization. PMID- 27399725 TI - Convergent Synthesis of Two Fluorescent Ebselen-Coumarin Heterodimers. AB - The organo-seleniumdrug ebselen exhibits a wide range of pharmacological effects that are predominantly due to its interference with redox systems catalyzed by seleno enzymes, e.g., glutathione peroxidase and thioredoxin reductase. Moreover, ebselen can covalently interact with thiol groups of several enzymes. According to its pleiotropic mode of action, ebselen has been investigated in clinical trials for the prevention and treatment of different ailments. Fluorescence labeled probes containing ebselen are expected to be suitable for further biological and medicinal studies. We therefore designed and synthesized two coumarin-tagged activity-based probes bearing the ebselen warhead. The heterodimers differ by the nature of the spacer structure, for which-in the second compound-a PEG/two-amide spacer was introduced. The interaction of this probe and of ebselen with two cysteine proteases was investigated. PMID- 27399726 TI - Electrospinning of Nanodiamond-Modified Polysaccharide Nanofibers with Physico Mechanical Properties Close to Natural Skins. AB - Electrospinning of biopolymers has gained significant interest for the fabrication of fibrous mats for potential applications in tissue engineering, particularly for wound dressing and skin regeneration. In this study, for the first time, we report successful electrospinning of chitosan-based biopolymers containing bacterial cellulous (33 wt %) and medical grade nanodiamonds (MND) (3 nm; up to 3 wt %). Morphological studies by scanning electron microscopy showed that long and uniform fibers with controllable diameters from 80 to 170 nm were prepared. Introducing diamond nanoparticles facilitated the electrospinning process with a decrease in the size of fibers. Fourier transform infrared spectroscopy determined hydrogen bonding between the polymeric matrix and functional groups of MND. It was also found that beyond 1 wt % MND, percolation networks of nanoparticles were formed which affected the properties of the nanofibrous mats. Uniaxial tensile testing of the woven mats determined significant enhancement of the strength (from 13 MPa to 25 MP) by dispersion of 1 wt % MND. The hydrophilicity of the mats was also remarkably improved, which was favorable for cell attachment. The water vapor permeability was tailorable in the range of 342 to 423 ug.Pa(-1).s(-1).m(-1). The nanodiamond-modified mats are potentially suitable for wound healing applications. PMID- 27399727 TI - Anticancer Effect of Fucoidan on DU-145 Prostate Cancer Cells through Inhibition of PI3K/Akt and MAPK Pathway Expression. AB - In this study, we showed that PI3K/Akt signaling mediates fucoidan's anticancer effects on prostate cancer cells, including suppression of proliferation. Fucoidan significantly decreased viability of DU-145 cancer cells in a concentration-dependent manner as shown by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay. The drug also significantly increased chromatin condensation, which indicates apoptosis, in a concentration-dependent manner as shown by DAPI (4',6-diamidino-2-phenylindole) staining. Fucoidan increased expression of Bax, cleaved poly-ADP ribose polymerase and cleaved caspase-9, and decreased of the Bcl-2, p-Akt, p-PI3K, p-P38, and p-ERK in a concentration-dependent manner. In vivo, fucoidan (at 5 and 10 mg/kg) significantly decreased tumor volume, and increased apoptosis as assessed by the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, confirming the tumor inhibitory effect. The drug also increased expression of p Akt and p-ERK as shown by immunohistochemistry staining. Therefore, fucoidan may be a promising cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human prostate cancer cells. PMID- 27399728 TI - To Pee, or Not to Pee: A Review on Envenomation and Treatment in European Jellyfish Species. AB - There is a growing cause for concern on envenoming European species because of jellyfish blooms, climate change and globalization displacing species. Treatment of envenomation involves the prevention of further nematocyst release and relieving local and systemic symptoms. Many anecdotal treatments are available but species-specific first aid response is essential for effective treatment. However, species identification is difficult in most cases. There is evidence that oral analgesics, seawater, baking soda slurry and 42-45 degrees C hot water are effective against nematocyst inhibition and giving pain relief. The application of topical vinegar for 30 s is effective on stings of specific species. Treatments, which produce osmotic or pressure changes can exacerbate the initial sting and aggravate symptoms, common among many anecdotal treatments. Most available therapies are based on weak evidence and thus it is strongly recommended that randomized clinical trials are undertaken. We recommend a vital increase in directed research on the effect of environmental factors on envenoming mechanisms and to establish a species-specific treatment. Adequate signage on jellyfish stings and standardized first aid protocols with emphasis on protective equipment and avoidance of jellyfish to minimize cases should be implemented in areas at risk. PMID- 27399729 TI - Screening of Diatom Strains and Characterization of Cyclotella cryptica as A Potential Fucoxanthin Producer. AB - Fucoxanthin has been receiving ever-increasing interest due to its broad health beneficial effects. Currently, seaweeds are the predominant source of natural fucoxanthin. However, the disappointingly low fucoxanthin content has impeded their use, driving the exploration of alternative fucoxanthin producers. In the present study, thirteen diatom strains were evaluated with respect to growth and fucoxanthin production potential. Cyclotella cryptica (CCMP 333), which grew well for fucoxanthin production under both photoautotrophic and heterotrophic growth conditions, was selected for further investigation. The supply of nitrate and light individually or in combination were all found to promote growth and fucoxanthin accumulation. When transferring heterotrophic cultures to light, fucoxanthin responded differentially to light intensities and was impaired by higher light intensity with a concomitant increase in diadinoxanthin and diatoxanthin, indicative of the modulation of Diadinoxanthin Cycle to cope with the light stress. Taken together, we, for the first time, performed the screening of diatom strains for fucoxanthin production potential and investigated in detail the effect of nutritional and environmental factors on C. cryptica growth and fucoxanthin accumulation. These results provide valuable implications into future engineering of C. cryptica culture parameters for improved fucoxanthin production and C. cryptica may emerge as a promising microalgal source of fucoxanthin. PMID- 27399730 TI - Antiproliferative Scalarane-Based Metabolites from the Red Sea Sponge Hyrtios erectus. AB - Two new sesterterpenes analogs, namely, 12-acetoxy,16-epi-hyrtiolide (1) and 12beta-acetoxy,16beta-methoxy,20alpha-hydroxy-17-scalaren-19,20-olide (2), containing a scalarane-based framework along with seven previously reported scalarane-type sesterterpenes (3-9) have been isolated from the sponge Hyrtios erectus (order Dictyoceratida) collected from the Red Sea, Egypt. The structures of the isolated compounds were elucidated on the basis of their spectroscopic data and comparison with reported NMR data. Compounds 1-9 exhibited considerable antiproliferative activity against breast adenocarcinoma (MCF-7), colorectal carcinoma (HCT-116) and hepatocellular carcinoma cells (HepG2). Compounds 3, 5 and 9 were selected for subsequent investigations regarding their mechanism of cell death induction (differential apoptosis/necrosis assessment) and their influence on cell cycle distribution. PMID- 27399732 TI - Prescribing Patterns in Outpatient Clinics of Township Hospitals in China: A Comparative Study before and after the 2009 Health System Reform. AB - OBJECTIVE: China introduced a series of health reforms in 2009, including a national essential medicines policy and a medical insurance system for primary care institutions. This study aimed to determine the changing prescribing patterns associated with those reforms in township hospitals. METHODS: A multi stage stratified random cluster sampling method was adopted to identify 29 township hospitals from six counties in three provinces. A total of 2899 prescriptions were collected from the participating township hospitals using a systematic random sampling strategy. Seven prescribing indicators were calculated and compared between 2008 and 2013, assessing use of medicines (antibiotics and adrenal corticosteroids) and polypharmacy, administration route of medicines (injections), and affordability of medicines. RESULTS: Significant changes in prescribing patterns were found. The average number of medicines and costs per prescription dropped by about 50%. The percentage of prescriptions requiring antibiotics declined from 54% to 38%. The percentage of prescriptions requiring adrenal corticosteroid declined from 14% to 4%. The percentage of prescriptions requiring injections declined from 54% to 25%. Despite similar changing patterns, significant regional differences were observed. CONCLUSIONS: Significant changes in prescribing patterns are evident in township hospitals in China. Overprescription of antibiotics, injections and adrenal corticosteroids has been reduced. However, salient regional disparities still exist. Further studies are needed to determine potential shifts in the risk of the inappropriate use of medicines from primary care settings to metropolitan hospitals. PMID- 27399731 TI - Spotlight on Antimicrobial Metabolites from the Marine Bacteria Pseudoalteromonas: Chemodiversity and Ecological Significance. AB - This review is dedicated to the antimicrobial metabolite-producing Pseudoalteromonas strains. The genus Pseudoalteromonas hosts 41 species, among which 16 are antimicrobial metabolite producers. To date, a total of 69 antimicrobial compounds belonging to 18 different families have been documented. They are classified into alkaloids, polyketides, and peptides. Finally as Pseudoalteromonas strains are frequently associated with macroorganisms, we can discuss the ecological significance of antimicrobial Pseudoalteromonas as part of the resident microbiota. PMID- 27399733 TI - Air Pressure, Humidity and Stroke Occurrence: A Systematic Review and Meta Analysis. AB - BACKGROUND/AIMS: An influence of climate upon stroke risk is biologically plausible and supported by epidemiological evidence. We aimed to determine whether air pressure (AP) and humidity are associated with hospital stroke admission. METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and GEOBASE, from inception to 16 October 2015 to identify relevant population-based observational studies. Where possible, data were pooled for meta analysis with odds ratios (OR) and corresponding 95% confidence intervals (CI) by means of the random-effect method. RESULTS: We included 11 studies with a total of 314,385 patients. The effect of AP was varied across studies for ischemic stroke (IS) and subarachnoid haemorrhage (SAH). Pooled ORs (95%CI) associated with 1 hPa increase in AP for the risk of IS, intracerebral hemorrhage (ICH) and SAH were 1.00 (0.99-1.01), 1.01 (0.99-1.02) and 1.02 (0.97-1.07) respectively. The pooled ORs (95%CI) associated with 1 percent increase in humidity for the risk of IS and ICH were 1.00 (1.00-1.01) and 1.00 (0.99-1.01) respectively. CONCLUSION: This review shows that there is no evidence of a relationship between AP or humidity and the occurrence of hospital admission for stroke. Further research is needed to clarify the extent and nature of any relationship between AP, humidity and stroke in different geographical areas. PMID- 27399734 TI - Associations between Dietary Intake and Urinary Bisphenol A and Phthalates Levels in Korean Women of Reproductive Age. AB - Human exposure to Bisphenol A (BPA) and phthalates is a growing concern due to their association with harmful effects on human health, including a variety of disorders of the female reproductive system. The objective of this study was to investigate the association between food intake and urinary BPA and phthalates in Korean women of reproductive age. A cross-sectional study was conducted with 305 reproductive aged (30-49 years) females in Korea. Dietary intake was assessed using 24 h dietary recall, and urinary BPA and particular phthalates were measured using high performance liquid chromatography tandem mass spectrometry. After adjusting for covariates, beverage intake was positively associated with urinary BPA, and egg and egg product intake was negatively associated with urinary mono-n-butyl phthalate (MnBP) as well as mono (2-ethyl-5-oxohexyl) phthalate (MEOHP). Odds ratio for high BPA level (>=90th percentile) in women with >100 g of beverage consumption was significantly higher than for those who consumed <=100 g. These results suggest that, in Korean women of reproductive age, some foods such as beverages and egg may be associated with body burdens of BPA, MnBP, MEHHP and MEOHP. PMID- 27399736 TI - Understanding Relationships between Health, Ethnicity, Place and the Role of Urban Green Space in Deprived Urban Communities. AB - Very little is known about how differences in use and perceptions of urban green space impact on the general health of black and minority ethnic (BME) groups. BME groups in the UK suffer from poorer health and a wide range of environmental inequalities that include poorer access to urban green space and poorer quality of green space provision. This study used a household questionnaire (n = 523) to explore the relationship between general health and a range of individual, social and physical environmental predictors in deprived white British and BME groups living in ethnically diverse cities in England. Results from Chi-Squared Automatic Interaction Detection (CHAID) segmentation analyses identified three distinct general health segments in our sample ranging from "very good" health (people of Indian origin), to "good" health (white British), and "poor" health (people of African-Caribbean, Bangladeshi, Pakistani origin and other BME groups), labelled "Mixed BME" in the analyses. Correlated Component Regression analyses explored predictors of general health for each group. Common predictors of general health across all groups were age, disability, and levels of physical activity. However, social and environmental predictors of general health including use and perceptions of urban green space-varied among the three groups. For white British people, social characteristics of place (i.e., place belonging, levels of neighbourhood trust, loneliness) ranked most highly as predictors of general health, whilst the quality of, access to and the use of urban green space was a significant predictor of general health for the poorest health group only, i.e., in "Mixed BME". Results are discussed from the perspective of differences in use and perceptions of urban green space amongst ethnic groups. We conclude that health and recreation policy in the UK needs to give greater attention to the provision of local green space amongst poor BME communities since this can play an important role in helping address the health inequalities experienced by these groups. PMID- 27399735 TI - Evaluation of the Effectiveness of Tai Chi versus Brisk Walking in Reducing Cardiovascular Risk Factors: Protocol for a Ranomized Controlled Trial. AB - Physical inactivity is one of the major modifiable lifestyle risk factors for cardiovascular disease (CVD). This protocol aims to evaluate the effectiveness of Tai Chi versus brisk walking in reducing CVD risk factors. This is a randomized controlled trial with three arms, namely, Tai Chi group, walking group, and control group. The Tai Chi group will receive Tai Chi training, which consists of two 60-min sessions each week for three months, and self-practice for 30 min every day. The walking group will perform brisk walking for 30 min every day. The control group will receive their usual care. 246 subjects with CVD risk factors will be recruited from two outpatient clinics. The primary outcome is blood pressure. Secondary outcomes include fasting blood for lipid profile, sugar and glycated haemoglobin (HbA1c); body mass index, waist circumference, body fat percentage; perceived stress level and quality of life. Data collections will be conducted at baseline, 3-month, 6-month and 9-month. Generalized estimating equations model will be used to compare the changes in outcomes across time between groups. It is expected that both the Tai Chi and walking groups could maintain better health and have improved quality of life, and that Tai Chi will be more effective than brisk walking in reducing CVD risk factors. PMID- 27399738 TI - Ontario's Experience of Wind Energy Development as Seen through the Lens of Human Health and Environmental Justice. AB - The province of Ontario has shown great commitment towards the development of renewable energy and, specifically, wind power. Fuelled by the Green Energy Act (GEA) of 2009, the Province has emerged as Canada's leader in wind energy development (WED). Nonetheless, Ontario's WED trajectory is characterized by social conflicts, particularly around environmental health. Utilizing the Social Amplification of Risk Framework, this paper presents an eight-year longitudinal media content analysis conducted to understand the role Ontario's media may be playing in both reflecting and shaping public perceptions of wind turbine health risks. We find that before and after the GEA, instances of health risk amplification were far greater than attenuations in both quantity and quality. Discourses that amplified turbine health risks often simultaneously highlighted injustices in the WED process, especially after the GEA. Based on these findings, we suggest that Ontario's media may be amplifying perceptions of wind turbine health risks within the public domain. We conclude with policy recommendations around public engagement for more just WED. PMID- 27399737 TI - Prediction of Massive Transfusion in Trauma Patients with Shock Index, Modified Shock Index, and Age Shock Index. AB - OBJECTIVES: The shock index (SI) and its derivations, the modified shock index (MSI) and the age shock index (Age SI), have been used to identify trauma patients with unstable hemodynamic status. The aim of this study was to evaluate their use in predicting the requirement for massive transfusion (MT) in trauma patients upon arrival at the hospital. PARTICIPANTS: A patient receiving transfusion of 10 or more units of packed red blood cells or whole blood within 24 h of arrival at the emergency department was defined as having received MT. Detailed data of 2490 patients hospitalized for trauma between 1 January 2009, and 31 December 2014, who had received blood transfusion within 24 h of arrival at the emergency department, were retrieved from the Trauma Registry System of a level I regional trauma center. These included 99 patients who received MT and 2391 patients who did not. Patients with incomplete registration data were excluded from the study. The two-sided Fisher exact test or Pearson chi-square test were used to compare categorical data. The unpaired Student t-test was used to analyze normally distributed continuous data, and the Mann-Whitney U-test was used to compare non-normally distributed data. Parameters including systolic blood pressure (SBP), heart rate (HR), hemoglobin level (Hb), base deficit (BD), SI, MSI, and Age SI that could provide cut-off points for predicting the patients' probability of receiving MT were identified by the development of specific receiver operating characteristic (ROC) curves. High accuracy was defined as an area under the curve (AUC) of more than 0.9, moderate accuracy was defined as an AUC between 0.9 and 0.7, and low accuracy was defined as an AUC less than 0.7. RESULTS: In addition to a significantly higher Injury Severity Score (ISS) and worse outcome, the patients requiring MT presented with a significantly higher HR and lower SBP, Hb, and BD, as well as significantly increased SI, MSI, and Age SI. Among these, only four parameters (SBP, BD, SI, and MSI) had a discriminating power of moderate accuracy (AUC > 0.7) as would be expected. A SI of 0.95 and a MSI of 1.15 were identified as the cut-off points for predicting the requirement of MT, with an AUC of 0.760 (sensitivity: 0.563 and specificity: 0.876) and 0.756 (sensitivity: 0.615 and specificity: 0.823), respectively. However, in the groups of patients with comorbidities such as hypertension, diabetes mellitus, or coronary artery disease, the discriminating power of these three indices in predicting the requirement of MT was compromised. CONCLUSIONS: This study reveals that the SI is moderately accurate in predicting the need for MT. However, this predictive power may be compromised in patients with HTN, DM or CAD. Moreover, the more complex calculations of MSI and Age SI failed to provide better discriminating power than the SI. PMID- 27399739 TI - Children's Understanding of No Diving Warning Signs: Implications for Preventing Childhood Injury. AB - The current study examined children's understanding of No Diving warning signs. Normally-developing 7 to 10 year olds were asked questions to assess their understanding of text, images, and main messages on No Diving warning signs. These structured interviews were audio recorded and responses were later coded. Results revealed that children understood the behavior advised against (diving), why it is prohibited (can hit head on the bottom), and what can happen (serious injury including hospitalization). They understood that breaking your neck results in limitations in mobility and can occur from diving, but they did not anticipate that such an injury is likely to occur. There were no gender and few age differences, but diving experience was associated with children significantly downplaying their risk of injury. The findings suggest that having No Diving warning signs explicitly mention a broken neck, may serve to remind children of this potential consequence at the time of decision making. Active adult supervision is particularly important for children who have prior positive diving experiences. PMID- 27399741 TI - Caregiver Reports of Children's Activity Participation Following Serious Injury. AB - Paediatric trauma can result in significant levels of on-going disability. The aim of this study was to explore the restrictions on activity participation that children experience following serious injury from the perspective of their caregivers. We performed a thematic analysis of transcripts of semi-structured in depth interviews with the caregivers of 44 seriously injured children, conducted three-years after the injury, and purposively sampled from a population-based cohort study. Both temporary and on-going restrictions on school, sport, leisure and social activities were identified, some of which were imposed by caregivers, schools, or recommended by health providers. The perceived risk of further injury, physical restrictions, emotional state and fatigue levels were important influences on degrees of activity restriction. Children who were socially less engaged, especially those who were more severely injured, had difficulty making and retaining friends, and exhibited signs of depression or social withdrawal. The activities of pre-school children were strongly regulated by their caregivers, while school age children faced obstacles with participation in aspects such as study, sport, and peer and teacher relationships, affecting learning, school attendance and enjoyment. The findings highlight the need for primary prevention and reducing the impacts of serious injury throughout the continuum of care. PMID- 27399740 TI - Disparities in Under-Five Child Injury Mortality between Developing and Developed Countries: 1990-2013. AB - OBJECTIVE: Using estimates from the 2013 Global Burden of Disease (GBD) study, we update evidence on disparities in under-five child injury mortality between developing and developed countries from 1990 to 2013. METHODS: Mortality rates were accessed through the online visualization tool by the GBD study 2013 group. We calculated percent change in child injury mortality rates between 1990 and 2013. Data analysis was conducted separately for <1 year and 1-4 years to specify age differences in rate changes. RESULTS: Between 1990 and 2013, over 3-fold mortality gaps were observed between developing countries and developed countries for both age groups in the study time period. Similar decreases in injury rates were observed for developed and developing countries (<1 year: -50% vs. -50% respectively; 1-4 years: -56% vs. -58%). Differences in injury mortality changes during 1990-2013 between developing and developed nations varied with injury cause. There were greater reductions in mortality from transport injury, falls, poisoning, adverse effects of medical treatment, exposure to forces of nature, and collective violence and legal intervention in developed countries, whereas there were larger decreases in mortality from drowning, exposure to mechanical forces, and animal contact in developing countries. Country-specific analysis showed large variations across countries for both injury mortality and changes in injury mortality between 1990 and 2013. CONCLUSIONS: Sustained higher child injury mortality during 1990-2013 for developing countries merits the attention of the global injury prevention community. Countries that have high injury mortality can benefit from the success of other countries. PMID- 27399742 TI - Patterns of Injury in Hospitalised One-Year-Old Children: Analysis by Trimester of Age Using Coded Data and Textual Description. AB - The second year of life is a time of rapid developmental changes. This paper aims to describe the pattern of unintentional injuries to one-year old children in three-month age bands to better understand the risks associated with developmental stages and, therefore, identify opportunities for proactive prevention. Injury surveillance data were used to identify children admitted to hospital in Queensland, Australia for an unintentional injury from 2002-2012. Falls were the most common injury, followed by burns and scalds, contact injuries and poisonings. Falls and contact injuries remained roughly constant by age, burns and scalds decreased and poisonings (by medications) increased. Animal- and transport-related injuries also became more common, immersions and other threats to breathing less common. Within the falls and contact categories falls from play equipment and injuries due to contact with persons increased, while falls down stairs and catching fingers in doors decreased. The pattern of injuries varies over the second year of life and is clearly linked to the child's increasing mobility and boldness. Preventive measures for young children need to be designed and evaluated-with their developmental stage in mind, using a variety of strategies, including opportunistic, developmentally specific education of parents; and practitioners should also consider potential for lapses in supervision and possible intentional injury in all injury assessments. PMID- 27399743 TI - Pediatric Canadian Triage and Acuity Scale (PaedsCTAS) as a Measure of Injury Severity. AB - This research explored whether the pediatric version of the Canadian Triage Acuity Scale (PaedsCTAS) represented a valid alternative indicator for surveillance of injury severity. Every patient presenting in a Canadian emergency department is assigned a CTAS or PaedsCTAS score in order to prioritize access to care and to predict the nature and scope of care that is likely to be required. The five-level PaedsCTAS score ranges from I (resuscitation) to V (non-urgent). A total of 256 children, 0 to 17-years-old, who attended a pediatric hospital for an injury were followed longitudinally. Of these children, 32.4% (n = 83) were hospitalized and 67.6% (n = 173) were treated in the emergency department and released. They completed the PedsQL(TM), a validated measure of health related quality of life, at baseline (pre-injury status), one-month, four- to six-months, and 12-months post-injury. In this secondary data analysis, PaedsCTAS was found to be significantly associated with hospitalization and length of stay, sensitive to the differences between PaedsCTAS II and III, and related to physical but not psychosocial HRQoL. The findings suggest that PaedsCTAS may be a useful proxy measure of injury severity to supplement or replace hospitalization status and/or length of stay, currently proxy measures. PMID- 27399744 TI - The Extent of Consumer Product Involvement in Paediatric Injuries. AB - A challenge in utilising health sector injury data for Product Safety purposes is that clinically coded data have limited ability to inform regulators about product involvement in injury events, given data entry is bound by a predefined set of codes. Text narratives collected in emergency departments can potentially address this limitation by providing relevant product information with additional accompanying context. This study aims to identify and quantify consumer product involvement in paediatric injuries recorded in emergency department-based injury surveillance data. A total of 7743 paediatric injuries were randomly selected from Queensland Injury Surveillance Unit database and associated text narratives were manually reviewed to determine product involvement in the injury event. A Product Involvement Factor classification system was used to categorise these injury cases. Overall, 44% of all reviewed cases were associated with consumer products, with proximity factor (25%) being identified as the most common involvement of a product in an injury event. Only 6% were established as being directly due to the product. The study highlights the importance of utilising injury data to inform product safety initiatives where text narratives can be used to identify the type and involvement of products in injury cases. PMID- 27399745 TI - Barriers and Enablers to Enacting Child and Youth Related Injury Prevention Legislation in Canada. AB - Injury prevention policy is crucial for the safety of Canada's children; however legislation is not adopted uniformly across the country. This study aimed to identify key barriers and enablers to enacting injury prevention legislation. Purposive snowball sampling identified individuals involved in injury prevention throughout Canada. An online survey asked respondents to identify policies that were relevant to them, and whether legislation existed in their province. Respondents rated the importance of barriers or enablers using a 5-point Likert type scale and included open-ended comments. Fifty-seven respondents identified the most common injury topics: bicycle helmets (44, 77%), cell phone-distracted driving (36, 63%), booster seats (28, 49%), ski helmets (24, 42%), and graduated driver's licensing (21, 37%). The top enablers were research/surveillance, managerial/political support and professional group consultation, with much variability between injury topics. Open-ended comments emphasized the importance of a united opinion as an enabler and barriers included costs of protective equipment and inadequate enforcement of legislation. The results highlighted the importance of strategies that include research, management and community collaboration and that injury prevention topics should be addressed individually as information may be lost if topics are considered together. Findings can inform the process of turning injury prevention evidence into action. PMID- 27399746 TI - Predictors of FIFA 11+ Implementation Intention in Female Adolescent Soccer: An Application of the Health Action Process Approach (HAPA) Model. AB - The Federation Internationale de Football (FIFA) 11+ warm-up program is efficacious at preventing lower limb injury in youth soccer; however, there has been poor adoption of the program in the community. The purpose of this study was to determine the utility of the Health Action Process Approach (HAPA) behavior change model in predicting intention to use the FIFA 11+ in a sample of 12 youth soccer teams (coaches n = 10; 12-16 year old female players n = 200). A bespoke cross-sectional questionnaire measured pre-season risk perceptions, outcome expectancies, task self-efficacy, facilitators, barriers, and FIFA 11+ implementation intention. Most coaches (90.0%) and players (80.0%) expected the program to reduce injury risk but reported limited intention to use it. Player data demonstrated an acceptable fit to the hypothesized model (standardized root mean square residual (SRMR) = 0.08; root mean square of error of approximation (RMSEA) = 0.06 (0.047-0.080); comparative fit index (CFI) = 0.93; Tucker Lewis index (TLI) = 0.91) Task self-efficacy (beta = 0.53, p <= 0.01) and outcome expectancies (beta = 0.13 p <= 0.05) were positively associated with intention, but risk perceptions were not (beta = -0.02). The findings suggest that the HAPA model is appropriate for use in this context, and highlight the need to target task self-efficacy and outcome expectancies in FIFA 11+ implementation strategies. PMID- 27399747 TI - An Analysis of Children Left Unattended in Parked Motor Vehicles in Brazil. AB - Our study investigates the incidence of children left unattended in parked motor vehicles in Brazil. These events have been widely explored in the United States but less so abroad, and never in Brazil. Over the period from 2006 to 2015, we collected data from news reports on 31 cases, including 21 fatalities. The circumstances mostly involved a caregiver, especially a parent, forgetting the child (71%), but cases also included the child being intentionally left in the vehicle (23%) or gaining access to the vehicle (3%). Children tended to be forgotten more frequently in fatal cases (86%), particularly on the way to daycare, than non-fatal incidents where circumstances were more evenly distributed between forgetting (40%) and being intentionally left behind (50%). Incidents occurred throughout the country but mostly in the southeastern region near the city of Sao Paulo. Additionally, the danger for children is present year round as we observed cases in every season, albeit with a peak in the summer. This heat-related hazard is not well recognized across Brazil and we recommend increasing awareness through education. Further, given the high percentage of cases involving parents forgetting to leave their children at daycare, we recommend arrangements between daycare providers and parents to communicate when a child does not attend as expected. PMID- 27399748 TI - Disparities in Paediatric Injury Mortality between Aboriginal and Non-Aboriginal Populations in British Columbia, 2001-2009. AB - Injury is the leading cause of death among children and youth in Canada. Significant disparities in injury mortality rates have been observed between Aboriginal and non-Aboriginal populations, but little is known about the age-, sex-, and mechanism-specific patterns of injury causing death. This study examines paediatric mortality in British Columbia from 2001 to 2009 using comprehensive vital statistics registry data. We highlight important disparities in Aboriginal and non-Aboriginal mortality rates, and use the Preventable Years of Life Lost (PrYLL) metric to identify differences between age groups and the mechanisms of injury causing death. A significantly greater age-adjusted mortality rate was observed among Aboriginal children (OR = 2.08, 95% CI: 1.41, 3.06), and significantly higher rates of death due to assault, suffocation, and fire were detected for specific age groups. Mapped results highlight regional disparities in PrYLL across the province, which may reflect higher Aboriginal populations in rural and remote areas. Crucially, these disparities underscore the need for community-specific injury prevention policies, particularly in regions with high PrYLL. PMID- 27399749 TI - Challenges in the Accurate Surveillance of Booster Seat and Bicycle Helmet Usage by Children: Lessons from the Field. AB - Motor vehicle collisions and bicycle collisions and falls are a leading cause of death by preventable injury for children. In order to design, implement and evaluate campaigns and programs aimed at improving child safety, accurate surveillance is needed. This paper examined the challenges that confront efforts to collect surveillance data relevant to child traffic safety, including observation, interview, and focus group methods. Strategies to address key challenges in order to improve the efficiency and accuracy of surveillance methods were recommended. The potential for new technology to enhance existing surveillance methods was also explored. PMID- 27399750 TI - The Incidence and Types of Physical Contact Associated with Body Checking Regulation Experience in 13-14 Year Old Ice Hockey Players. AB - BACKGROUND: Ice hockey has one of the highest sport participation and injury rates in youth in Canada. Body checking (BC) is the predominant mechanism of injury in leagues in which it is permitted. The objectives of this study were to determine whether the incidence and types of physical contact differ for Bantam players (aged 13-14 years) who were exposed to BC at Pee Wee level (aged 11-12 years) in Calgary, Alberta versus Bantam players who were not exposed to BC at Pee Wee level in Quebec City, Quebec. All teams were exposed to BC at bantam level; METHODS: A cohort study was conducted in Quebec City and Calgary. Sixteen games for Calgary and 15 for Quebec City were randomly selected and analysed with a validated observation system to quantify five intensities of physical contact and to observe different types of physical contact such as slashing and holding; RESULTS: A total of 5610 incidences of physical contact with the trunk and 3429 other types of physical contact were observed. Very light intensity trunk contact was more frequent in Calgary (adjusted incidence RR (ARR): 1.71; 95% CI: 1.28 2.29). Holding (ARR: 1.04; 95% CI: 1.02-1.07) and slashing (ARR: 1.38; 95% CI: 1.07-1.77) were more frequent in Calgary; CONCLUSION: RESULTS suggest that players' physical contacts differ between Bantam leagues in which BC was permitted at Pee Wee level and leagues in which it was not permitted until Bantam level. PMID- 27399751 TI - Types of Obesity and Its Association with the Clustering of Cardiovascular Disease Risk Factors in Jilin Province of China. AB - Cardiovascular disease (CVD) has become a serious public health problem in recent years in China. Aggregation of CVD risk factors in one individual increases the risk of CVD and the risk increases substantially with each additional risk factor. This study aims to explore the relationship between the number of clustered CVD risk factors and different types of obesity. A multistage stratified random cluster sampling design was used in this population-based cross sectional study in 2012. Information was collected by face to face interviews. One-way analysis of variance (ANOVA), chi-square test, Kruskal-Wallis test and multiple logistic regression were used in this study. The prevalence of general obesity, central obesity and compound obesity were 0.3%, 36.1% and 14.7%, respectively. The prevalence of hypertension, hyperlipidemia and diabetes in the compound obesity group were higher than those in other groups (compound obesity > central obesity > general obesity > non-obesity), while smoking rate in the non obesity group was higher than those in other groups (non-obesity > general obesity > central obesity > compound obesity). People with obesity were more likely to have one or more CVD risk factor compared with non-obesity subjects (general obesity (OR: 2.27, 95% CI: 1.13-4.56), central obesity (OR: 2.64, 95% CI: 2.41-2.89), compound obesity (OR: 5.09, 95% CI: 4.38-5.90). The results were similar when the number of clustered CVD risk factors was >= 2 and >= 3. As a conclusion, more than half of the residents in Jilin Province have a problem of obesity, especially central obesity. Government and health department should take measures to improve people's awareness of central obesity in Jilin Province of China. The prevalence of hypertension, hyperlipidemia and diabetes are associated with obesity types. Compound obesity has a greater risk to cluster multiple CVD risk factors than central obesity and general obesity. Taking measures to control obesity will reduce the prevalence of CVD in Jilin Province. PMID- 27399752 TI - Patterns and Associated Factors of Caesarean Delivery Intention among Expectant Mothers in China: Implications from the Implementation of China's New National Two-Child Policy. AB - OBJECTIVE: This study explores the basic demographic characteristics of expectant mothers in the context of their intentions regarding mode of delivery, in particular, the preference for caesarean delivery, and analyzes the social and psychological factors that influence delivery preference. METHOD: A cross sectional survey of pregnant women was conducted during June to August in 2015. This study adopted a stratified sampling method, and 16 representative hospitals in five provinces of China were included. RESULTS: 1755 and 590 of expectant mothers in their first and second pregnancies, respectively, were enrolled in this study. 354 (15.10%) intended to deliver by caesarean section and 585 (24.95%) participants were uncertain prior to delivery. 156 (8.89%) of expectant mothers in their first pregnancy and 198 (33.56%) expectant mothers in their second pregnancy intended to deliver by caesarean section. Ordinal logistic regression analysis found that nationality, parity, trimester of pregnancy, and advanced maternal age were factors associated with intention to deliver by caesarean (ordered logistic regression/three-level caesarean delivery intention criterion; odds ratios p < 0.05). CONCLUSIONS: 8.89% of first pregnancy expectant mothers and 33.56% of second pregnancy expectant mothers intended to deliver by caesarean section. Any intervention program to reduce the rate of Caesarean delivery should focus on the Han population, older pregnant women, and expectant mothers in their second pregnancy, at an early gestation. PMID- 27399753 TI - Effects of Dissolved Organic Matter on Uptake and Translocation of Lead in Brassica chinensis and Potential Health Risk of Pb. AB - Dissolved organic matter (DOM) can affect the bioavailability of heavy metals in soil, especially in soils used for vegetable production, where intensive organic fertilization is applied. The present study examined the effects of DOM derived from commercial organic fertilizers (COF), cow manure (COM) and chicken manure (CHM), on uptake and translocation of lead (Pb) in Brassica chinensis in a pot experiment. The results indicate that DOM derived from CHM (DOMCHM) significantly increased Pb concentrations in roots of B. chinensis (p < 0.05). By contrast, there was no significant increase in shoot Pb concentration for all the DOM treatments except the high DOMCHM treatment in the soil with 800 mg.kg(-1) Pb. Consistent with the Pb concentrations in shoots, translocation factor of Pb from soil to shoot and specific lead uptake (SLU) by B. chinensis were significantly increased for the high DOMCHM treatment in the high Pb soil, but not for other DOM treatments. Based on the results of this study, the application of DOM to the soil with 800 mg.kg(-1) Pb could result in an increase in total Pb annually ingested by the inhabitants of Nanjing City in the range of 2018-9640 kg, with the highest estimates resulting from the high DOMCHM treatment. This study suggests the risk may rise under some conditions as indicated in the high DOMCHM treatment and high Pb pollution level. PMID- 27399754 TI - Characteristics of Ambient Black Carbon Mass and Size-Resolved Particle Number Concentrations during Corn Straw Open-Field Burning Episode Observations at a Rural Site in Southern Taiwan. AB - Information on the effect of open-field burning of agricultural residues on ambient black carbon (BC) mass and size-resolved particle number concentrations is scarce. In this study, to understand the effect of such open-field burning on short-term air quality, real-time variations of the BC mass and size-resolved particle number concentrations were monitored before and during a corn straw open field burning episode at a rural site. Correlations between the BC mass and size resolved particle number concentrations during the episode were investigated. Moreover, the particle number size distribution and absorption Angstrom exponent were determined for obtaining the characteristics of aerosol emissions from the corn straw open-field burning. The results can be used to address public health concerns and as a reference for managing similar episodes of open-field burning of agricultural residues. PMID- 27399755 TI - Improving Environmental Health Literacy and Justice through Environmental Exposure Results Communication. AB - Understanding the short- and long-term impacts of a biomonitoring and exposure project and reporting personal results back to study participants is critical for guiding future efforts, especially in the context of environmental justice. The purpose of this study was to evaluate learning outcomes from environmental communication efforts and whether environmental health literacy goals were met in an environmental justice community. We conducted 14 interviews with parents who had participated in the University of Arizona's Metals Exposure Study in Homes and analyzed their responses using NVivo, a qualitative data management and analysis program. Key findings were that participants used the data to cope with their challenging circumstances, the majority of participants described changing their families' household behaviors, and participants reported specific interventions to reduce family exposures. The strength of this study is that it provides insight into what people learn and gain from such results communication efforts, what participants want to know, and what type of additional information participants need to advance their environmental health literacy. This information can help improve future report back efforts and advance environmental health and justice. PMID- 27399756 TI - Surveillance of Mosquitoes and Selected Arthropod-Borne Viruses in the Context of Milan EXPO 2015. AB - From 1 May 2015 to 31 October 2015 over 20 million visitors from all over the world visited the Universal Exhibition (EXPO) hosted by Milan (Lombardy region, Italy), raising concerns about the possible introduction of mosquito-borne diseases from endemic countries. The entomological surveillance protocol performed in Lombardy over the last three years was implemented in the EXPO area and in the two major regional airports using both Center for Disease Control CO2 and Biogents Sentinel traps. This surveillance aimed to estimate the presence and densities of putative vectors, and also to support investigations, including the vector species involved and area of diffusion, on the local spread of Chikungunya, Dengue and West Nile viruses (WNV) by competent vectors. From 3544 mosquitoes belonging to five different species, 28 pools of Culex spp. and 45 pools of Aedes spp. were screened for the presence of WNV, and for both Chikungunya and flaviviruses, respectively. The entomological surveillance highlighted a low density of potential vectors in the surveyed areas and did not reveal the presence of Chikungunya or Dengue viruses in the local competent vectors inside the EXPO area or in the two airports. In addition, the surveillance reported a low density of Culex spp. mosquitoes, which all tested negative for WNV. PMID- 27399757 TI - Impaired Expression of Cytokines as a Result of Viral Infections with an Emphasis on Small Ruminant Lentivirus Infection in Goats. AB - Knowing about the genes involved in immunity, and being able to identify the factors influencing their expressions, helps in gaining awareness of the immune processes. The qPCR method is a useful gene expression analysis tool, but studies on immune system genes are still limited, especially on the caprine immune system. Caprine arthritis encephalitis, a disease caused by small ruminant lentivirus (SRLV), causes economic losses in goat breeding, and there is no therapy against SRLV. The results of studies on vaccines against other viruses are promising. Moreover, the Marker-Assisted Selection strategy against SRLV is possible, as has been shown in sheep breeding. However, there are still many gaps in our knowledge on the caprine immune response to infection. All types of cytokines play pivotal roles in immunity, and SRLV infection influences the expression of many cytokines in different types of cells. This information encouraged the authors to examine the results of studies conducted on SRLV and other viral infections, with an emphasis on the expression of cytokine genes. This review attempts to summarize the results of studies on the expression of cytokines in the context of the SRLV infection. PMID- 27399759 TI - Effectiveness of Four Disinfectants against Ebola Virus on Different Materials. AB - The West Africa Ebola virus (EBOV) outbreak has highlighted the need for effective disinfectants capable of reducing viral load in a range of sample types, equipment and settings. Although chlorine-based products are widely used, they can also be damaging to equipment or apparatus that needs continuous use such as aircraft use for transportation of infected people. Two aircraft cleaning solutions were assessed alongside two common laboratory disinfectants in a contact kill assay with EBOV on two aircraft relevant materials representative of a porous and non-porous surface. A decimal log reduction of viral titre of 4 is required for a disinfectant to be deemed effective and two of the disinfectants fulfilled this criteria under the conditions tested. One product, Ardrox 6092, was found to perform similarly to sodium hypochlorite, but as it does not have the corrosive properties of sodium hypochlorite, it could be an alternative disinfectant solution to be used for decontamination of EBOV on sensitive apparatus. PMID- 27399758 TI - Recombinant Ranaviruses for Studying Evolution of Host-Pathogen Interactions in Ectothermic Vertebrates. AB - Ranaviruses (Iridoviridae) are large DNA viruses that are causing emerging infectious diseases at an alarming rate in both wild and captive cold blood vertebrate species all over the world. Although the general biology of these viruses that presents some similarities with poxvirus is characterized, many aspects of their replication cycles, host cell interactions and evolution still remain largely unclear, especially in vivo. Over several years, strategies to generate site-specific ranavirus recombinant, either expressing fluorescent reporter genes or deficient for particular viral genes, have been developed. We review here these strategies, the main ranavirus recombinants characterized and their usefulness for in vitro and in vivo studies. PMID- 27399760 TI - A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny. AB - Nef proteins from all primate Lentiviruses, including the simian immunodeficiency virus of chimpanzees (SIVcpz), increase viral progeny infectivity. However, the function of Nef involved with the increase in viral infectivity is still not completely understood. Nonetheless, until now, studies investigating the functions of Nef from SIVcpz have been conducted in the context of the HIV-1 proviruses. In an attempt to investigate the role played by Nef during the replication cycle of an SIVcpz, a Nef-defective derivative was obtained from the SIVcpzWTGab2 clone by introducing a frame shift mutation at a unique restriction site within the nef sequence. This nef-deleted clone expresses an N-terminal 74 amino acid truncated peptide of Nef and was named SIVcpz-tNef. We found that the SIVcpz-tNef does not behave as a classic nef-deleted HIV-1 or simian immunodeficiency virus of macaques SIVmac. Markedly, SIVcpz-tNef progeny from both Hek-293T and Molt producer cells were completely non-infectious. Moreover, the loss in infectivity of SIVcpz-tNef correlated with the inhibition of Gag and GagPol processing. A marked accumulation of Gag and very low levels of reverse transcriptase were detected in viral lysates. Furthermore, these observations were reproduced once the tNef peptide was expressed in trans both in SIVcpzDeltaNef and HIV-1WT expressing cells, demonstrating that the truncated peptide is a dominant negative for viral processing and infectivity for both SIVcpz and HIV-1. We demonstrated that the truncated Nef peptide binds to GagPol outside the protease region and by doing so probably blocks processing of both GagPol and Gag precursors at a very early stage. This study demonstrates for the first time that naturally-occurring Nef peptides can potently block lentiviral processing and infectivity. PMID- 27399761 TI - A Sequence-Independent Strategy for Amplification and Characterisation of Episomal Badnavirus Sequences Reveals Three Previously Uncharacterised Yam Badnaviruses. AB - Yam (Dioscorea spp.) plants are potentially hosts to a diverse range of badnavirus species (genus Badnavirus, family Caulimoviridae), but their detection is complicated by the existence of integrated badnavirus sequences in some yam genomes. To date, only two badnavirus genomes have been characterised, namely, Dioscorea bacilliform AL virus (DBALV) and Dioscorea bacilliform SN virus (DBSNV). A further 10 tentative species in yam have been described based on their partial reverse transcriptase (RT)-ribonuclease H (RNaseH) sequences, generically referred to here as Dioscorea bacilliform viruses (DBVs). Further characterisation of DBV species is necessary to determine which represent episomal viruses and which are only present as integrated badnavirus sequences in some yam genomes. In this study, a sequence-independent multiply-primed rolling circle amplification (RCA) method was evaluated for selective amplification of episomal DBV genomes. This resulted in the identification and characterisation of nine complete genomic sequences (7.4-7.7 kbp) of existing and previously undescribed DBV phylogenetic groups from Dioscorea alata and Dioscorea rotundata accessions. These new yam badnavirus genomes expand our understanding of the diversity and genomic organisation of DBVs, and assist the development of improved diagnostic tools. Our findings also suggest that mixed badnavirus infections occur relatively often in West African yam germplasm. PMID- 27399762 TI - Properties of African Cassava Mosaic Virus Capsid Protein Expressed in Fission Yeast. AB - The capsid proteins (CPs) of geminiviruses combine multiple functions for packaging the single-stranded viral genome, insect transmission and shuttling between the nucleus and the cytoplasm. African cassava mosaic virus (ACMV) CP was expressed in fission yeast, and purified by SDS gel electrophoresis. After tryptic digestion of this protein, mass spectrometry covered 85% of the amino acid sequence and detected three N-terminal phosphorylation sites (threonine 12, serines 25 and 62). Differential centrifugation of cell extracts separated the CP into two fractions, the supernatant and pellet. Upon isopycnic centrifugation of the supernatant, most of the CP accumulated at densities typical for free proteins, whereas the CP in the pellet fraction showed a partial binding to nucleic acids. Size-exclusion chromatography of the supernatant CP indicated high order complexes. In DNA binding assays, supernatant CP accelerated the migration of ssDNA in agarose gels, which is a first hint for particle formation. Correspondingly, CP shifted ssDNA to the expected densities of virus particles upon isopycnic centrifugation. Nevertheless, electron microscopy did not reveal any twin particles, which are characteristic for geminiviruses. PMID- 27399763 TI - Investigation of the Dermal Absorption and Irritation Potential of Sertaconazole Nitrate Anhydrous Gel. AB - Effective topical therapy of cutaneous fungal diseases requires the delivery of the active agent to the target site in adequate concentrations to produce a pharmacological effect and inhibit the growth of the pathogen. In addition, it is important to determine the concentration of the drug in the skin in order to evaluate the subsequent efficacy and potential toxicity for topical formulations. For this purpose, an anhydrous gel containing sertaconazole nitrate as a model drug was formulated and the amount of the drug in the skin was determined by in vitro tape stripping. The apparent diffusivity and partition coefficients were then calculated by a mathematical model describing the dermal absorption as passive diffusion through a pseudo-homogenous membrane. The skin irritation potential of the formulation was also assessed by using the in vitro EpidermTM model. An estimation of the dermal absorption parameters allowed us to evaluate drug transport across the stratum corneum following topical application. The estimated concentration for the formulation was found to be higher than the MIC100 at the target site which suggested its potential efficacy for treating fungal infections. The skin irritation test showed the formulation to be non irritating in nature. Thus, in vitro techniques can be used for laying the groundwork in developing efficient and non-toxic topical products. PMID- 27399764 TI - Association between Motives for Dish Choices during Home Meal Preparation and Weight Status in the NutriNet-Sante Study. AB - Although home cooking has been associated with a lower body mass index in a few studies, no data exists on the motives behind food dish choices during home meal preparation and on their association with overweight. This study aimed to evaluate this association in 50,003 participants from the NutriNet-Sante cohort. Dimensions underlying the importance of 27 criteria possibly influencing dish choices were determined using an exploratory factor analysis. The association between dish choice motives and overweight (including obesity) was estimated using logistic regression models adjusted for sociodemographic and lifestyle characteristics. Five dimensions of dishes choice motives emerged: healthy diet (e.g., "nutritional balance of the dish"), constraints (e.g., "my cooking skills"), pleasure (e.g., "originality of the dish"), specific diets (e.g., "my health status"), and organization (e.g., "what I planned to eat"). A negative association was observed between the healthy diet factor and being overweight (OR = 0.65 (95% CI (confidence interval): 0.62-0.67)), whereas a positive association appeared for factors regarding pleasure (OR = 1.14 (95% CI: 1.10-1.19)) and specific diets (OR = 1.19 (95% CI: 1.17-1.22)). No significant associations were observed for constraints and organization. The significant associations between dish choice motives and overweight suggested the interest of focusing on these motives in order to promote healthier food choices during home cooking. PMID- 27399765 TI - Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model. AB - While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and alpha-glucosidase (6.2% 11.5% inhibition; p < 0.05). Separately, all GJ extracts (10-100 uM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%-38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%-15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%-38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal. PMID- 27399766 TI - Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice. AB - The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID- 27399767 TI - Do Consumers Want More Nutritional and Health Information on Wine Labels? Insights from the EU and USA. AB - The global strategy to reduce the harmful use of alcohol launched in 2010 by the World Health Organization includes, amongst several areas of recommended actions, providing consumer information about, and labelling, alcoholic beverages to indicate alcohol-related harm. Labelling requirements worldwide for alcoholic drinks are currently quite diverse and somewhat limited compared to labelling on food products and on tobacco. In this context, the current paper contributes to the academic and political debate on the inclusion of nutritional and health information on wine labelling, providing some insights into consumer interest in, and preferences for, such information in four core wine-producing and -consuming countries: Italy, France, Spain, and the United States of America. A rating-based conjoint analysis was performed in order to ascertain consumer preferences for different formats of additional information on wine labels, and a segmentation of the sample was performed to determine the existence of homogeneous groups of consumers in relation to the degrees of usefulness attached to the nutritional and health information on wine labels. Our results highlight the interest expressed by European and United States consumers for introducing nutrition and health information on wine labels. However, the results of conjoint analysis show some significant differences among stated preferences of the information delivery modes in different countries. In addition, segmentation analysis reveal the existence of significant differences between consumer groups with respect to their interest in receiving additional information on wine labels. These differences are not only linked to the geographic origin of the consumers, or to socio-demographic variables, but are also related to wine consumption habits, attitudes towards nutritional information, and the degree of involvement with wine. This heterogeneity of consumer preferences indicates a need for a careful consideration of wine labelling regulations and merits further investigation in order to identify labelling guidelines in terms of the message content and presentation method to be used. PMID- 27399768 TI - Length Normalized Indices for Fat Mass and Fat-Free Mass in Preterm and Term Infants during the First Six Months of Life. AB - OBJECTIVE: Postnatal tissue accretion in preterm infants differs from those in utero, affecting body composition (BC) and lifelong morbidity. Length normalized BC data allows infants with different body lengths to be compared and followed longitudinally. This study aims to analyze BC of preterm and term infants during the first six months of life. METHODS: The BC data, measured using dual energy X ray absorptiometry, of 389 preterm and 132 term infants from four longitudinal studies were combined. Fat-mass/length2 (FMI) and fat-free mass/length2 (FFMI) for postmenstrual age were calculated after reaching full enteral feeding, at term and two further time points up to six months corrected age. RESULTS: Median FMI (preterm) increased from 0.4 kg/m2 at 30 weeks to 2.5, 4.3, and 4.8 kg/m2 compared to 1.7, 4.7, and 6 kg/m2 in term infants at 40, 52, and 64 weeks, respectively. Median FFMI (preterm) increased from 8.5 kg/m2 (30 weeks) to 11.4 kg/m2 (45 weeks) and remained constant thereafter, whereas term FFMI remained constant at 11 kg/m2 throughout the tested time points. CONCLUSION: The study provides a large dataset of length normalized BC indices. Followed longitudinally, term and preterm infants differ considerably during early infancy in the pattern of change in FMI and FFMI for age. PMID- 27399769 TI - Total Flavonoids from Rosa laevigata Michx Fruit Ameliorates Hepatic Ischemia/Reperfusion Injury through Inhibition of Oxidative Stress and Inflammation in Rats. AB - The effects of total flavonoids (TFs) from Rosa laevigata Michx fruit against liver damage and cerebral ischemia/reperfusion (I/R) injury have been reported, but its action on hepatic I/R injury remains unknown. In this work, the effects and possible mechanisms of TFs against hepatic I/R injury were examined using a 70% partial hepatic warm ischemia rat model. The results demonstrated TFs decreased serum aspartate transaminase (AST), alanine aminotransferase (ALT), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) activities, improved liver histopathology and ultrastructure through hematoxylin-eosin (HE) staining and electron microscope observation. In addition, TFs significantly decreased malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which indicated that TFs alleviated oxidative stress caused by I/R injury. RT-PCR results proved that TFs downregulated the gene levels of inflammatory factors including interleukin-1 beta (IL-1beta), interleukin-1 (IL-6), and tumor necrosis factor alpha (TNF-alpha). Further research indicated that TF-induced hepatoprotection was completed through inhibiting TLR4/MyD88 and activating Sirt1/Nrf2 signaling pathways. Blockade of the TLR4 pathway by TFs inhibited NF-kappaB and AP-1 transcriptional activities and inflammatory reaction. Activation of Sirt1/Nrf2 pathway by TFs increased the protein levels of HO-1 and GST to improve oxidative stress. Collectively, these findingsconfirmed the potent effects of TFs against hepatic I/R injury, which should be developed as a candidate for the prevention of this disease. PMID- 27399770 TI - The Stress Response Regulator AflSkn7 Influences Morphological Development, Stress Response, and Pathogenicity in the Fungus Aspergillus flavus. AB - This study focused on AflSkn7, which is a stress response regulator in the aflatoxin-producing Aspergillus flavus. The DeltaAflSkn7 mutants exhibited partially defective conidial formation and a complete inability to generate sclerotia, indicating AflSkn7 affects A. flavus asexual and sexual development. The mutants tolerated osmotic stress but were partially susceptible to the effects of cell wall stress. Additionally, the DeltaAflSkn7 mutants were especially sensitive to oxidative stress. These observations confirmed that AflSkn7 influences oxidative stress responses rather than osmotic stress responses. Additionally, AflSkn7 was observed to increase aflatoxin biosynthesis and seed infection rates. These results indicate AflSkn7 affects A. flavus morphological development, stress response, aflatoxin production, and pathogenicity. The results of this study may facilitate the development of new methods to manage A. flavus infections. PMID- 27399771 TI - Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai. AB - An enzyme in a nematocyst extract of the Nemopilema nomurai jellyfish, caught off the coast of the Republic of Korea, catalyzed the cleavage of chymotrypsin substrate in an amidolytic kinetic assay, and this activity was inhibited by the serine protease inhibitor, phenylmethanesulfonyl fluoride. We isolated the full length cDNA sequence of this enzyme, which contains 850 nucleotides, with an open reading frame of 801 encoding 266 amino acids. A blast analysis of the deduced amino acid sequence showed 41% identity with human chymotrypsin-like (CTRL) and the CTRL-1 precursor. Therefore, we designated this enzyme N. nomurai CTRL-1. The primary structure of N. nomurai CTRL-1 includes a leader peptide and a highly conserved catalytic triad of His(69), Asp(117), and Ser(216). The disulfide bonds of chymotrypsin and the substrate-binding sites are highly conserved compared with the CTRLs of other species, including mammalian species. Nemopilema nomurai CTRL-1 is evolutionarily more closely related to Actinopterygii than to Scyphozoan (Aurelia aurita) or Hydrozoan (Hydra vulgaris). The N. nomurai CTRL1 was amplified from the genomic DNA with PCR using specific primers designed based on the full-length cDNA, and then sequenced. The N. nomurai CTRL1 gene contains 2434 nucleotides and four distinct exons. The 5' donor splice (GT) and 3' acceptor splice sequences (AG) are wholly conserved. This is the first report of the CTRL1 gene and cDNA structures in the jellyfish N. nomurai. PMID- 27399772 TI - Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells. AB - Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma. PMID- 27399773 TI - Regulation of Toxin Production in Clostridium perfringens. AB - The Gram-positive anaerobic bacterium Clostridium perfringens is widely distributed in nature, especially in soil and the gastrointestinal tracts of humans and animals. C. perfringens causes gas gangrene and food poisoning, and it produces extracellular enzymes and toxins that are thought to act synergistically and contribute to its pathogenesis. A complicated regulatory network of toxin genes has been reported that includes a two-component system for regulatory RNA and cell-cell communication. It is necessary to clarify the global regulatory system of these genes in order to understand and treat the virulence of C. perfringens. We summarize the existing knowledge about the regulatory mechanisms here. PMID- 27399774 TI - How Safe Is Safe for Marine Toxins Monitoring? AB - Current regulation for marine toxins requires a monitoring method based on mass spectrometric analysis. This method is pre-targeted, hence after searching for pre-assigned masses, it identifies those compounds that were pre-defined with available calibrants. Therefore, the scope for detecting novel toxins which are not included in the monitoring protocol are very limited. In addition to this, there is a poor comprehension of the toxicity of some marine toxin groups. Also, the validity of the current approach is questioned by the lack of sufficient calibrants, and by the insufficient coverage by current legislation of the toxins reported to be present in shellfish. As an example, tetrodotoxin, palytoxin analogs, or cyclic imines are mentioned as indicators of gaps in the system that require a solid comprehension to assure consumers are protected. PMID- 27399776 TI - Distribution and Metabolism of Bt-Cry1Ac Toxin in Tissues and Organs of the Cotton Bollworm, Helicoverpa armigera. AB - Crystal (Cry) proteins derived from Bacillus thuringiensis (Bt) have been widely used in transgenic crops due to their toxicity against insect pests. However, the distribution and metabolism of these toxins in insect tissues and organs have remained obscure because the target insects do not ingest much toxin. In this study, several Cry1Ac-resistant strains of Helicoverpa armigera, fed artificial diets containing high doses of Cry1Ac toxin, were used to investigate the distribution and metabolism of Cry1Ac in their bodies. Cry1Ac was only detected in larvae, not in pupae or adults. Also, Cry1Ac passed through the midgut into other tissues, such as the hemolymph and fat body, but did not reach the larval integument. Metabolic tests revealed that Cry1Ac degraded most rapidly in the fat body, followed by the hemolymph, peritrophic membrane and its contents. The toxin was metabolized slowly in the midgut, but was degraded in all locations within 48 h. These findings will improve understanding of the functional mechanism of Bt toxins in target insects and the biotransfer and the bioaccumulation of Bt toxins in arthropod food webs in the Bt crop ecosystem. PMID- 27399775 TI - Staphylococcus aureus Toxins and Diabetic Foot Ulcers: Role in Pathogenesis and Interest in Diagnosis. AB - Infection of foot ulcers is a common, often severe and costly complication in diabetes. Diabetic foot infections (DFI) are mainly polymicrobial, and Staphylococcus aureus is the most frequent pathogen isolated. The numerous virulence factors and toxins produced by S. aureus during an infection are well characterized. However, some particular features could be observed in DFI. The aim of this review is to describe the role of S. aureus in DFI and the implication of its toxins in the establishment of the infection. Studies on this issue have helped to distinguish two S. aureus populations in DFI: toxinogenic S. aureus strains (harboring exfoliatin-, EDIN-, PVL- or TSST-encoding genes) and non-toxinogenic strains. Toxinogenic strains are often present in infections with a more severe grade and systemic impact, whereas non-toxinogenic strains seem to remain localized in deep structures and bone involving diabetic foot osteomyelitis. Testing the virulence profile of bacteria seems to be a promising way to predict the behavior of S. aureus in the chronic wounds. PMID- 27399778 TI - Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid. AB - Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (gamma-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee. PMID- 27399777 TI - Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms. AB - Central and South American pitvipers, belonging to the genera Bothrops and Bothriechis, have independently evolved arboreal tendencies. Little is known regarding the composition and activity of their venoms. In order to close this knowledge gap, venom proteomics and toxin activity of species of Bothriechis, and Bothrops (including Bothriopsis) were investigated through established analytical methods. A combination of proteomics and bioactivity techniques was used to demonstrate a similar diversification of venom composition between large and small species within Bothriechis and Bothriopsis. Increasing our understanding of the evolution of complex venom cocktails may facilitate future biodiscoveries. PMID- 27399779 TI - Baltikinin: A New Myotropic Tryptophyllin-3 Peptide Isolated from the Skin Secretion of the Purple-Sided Leaf Frog, Phyllomedusa baltea. AB - Here we report the identification of a novel tryptophyllin-3 peptide with arterial smooth muscle relaxation activity from the skin secretion of the purple sided leaf frog, Phyllomedusa baltea. This new peptide was named baltikinin and had the following primary structure, pGluDKPFGPPPIYPV, as determined by tandem mass spectrometry (MS/MS) fragmentation sequencing and from cloned skin precursor encoding cDNA. A synthetic replicate of baltikinin was found to have a similar potency to bradykinin in relaxing arterial smooth muscle (half maximal effective concentration (EC50) is 7.2 nM). These data illustrate how amphibian skin secretions can continue to provide novel potent peptides that act through functional targets in mammalian tissues. PMID- 27399782 TI - Stationary-Phase Mutagenesis in Stressed Bacillus subtilis Cells Operates by Mfd Dependent Mutagenic Pathways. AB - In replication-limited cells of Bacillus subtilis, Mfd is mutagenic at highly transcribed regions, even in the absence of bulky DNA lesions. However, the mechanism leading to increased mutagenesis through Mfd remains currently unknown. Here, we report that Mfd may promote mutagenesis in nutritionally stressed B. subtilis cells by coordinating error-prone repair events mediated by UvrA, MutY and PolI. Using a point-mutated gene conferring leucine auxotrophy as a genetic marker, it was found that the absence of UvrA reduced the Leu+ revertants and that a second mutation in mfd reduced mutagenesis further. Moreover, the mfd and polA mutants presented low but similar reversion frequencies compared to the parental strain. These results suggest that Mfd promotes mutagenic events that required the participation of NER pathway and PolI. Remarkably, this Mfd dependent mutagenic pathway was found to be epistatic onto MutY; however, whereas the MutY-dependent Leu+ reversions required Mfd, a direct interaction between these proteins was not apparent. In summary, our results support the concept that Mfd promotes mutagenesis in starved B. subtilis cells by coordinating both known and previously unknown Mfd-associated repair pathways. These mutagenic processes bias the production of genetic diversity towards highly transcribed regions in the genome. PMID- 27399783 TI - Pickleworm (Diaphania nitidalis Cramer) Neonate Feeding Preferences and the Implications for a Push-Pull Management System. AB - Push-pull cropping approaches for pest management target the oviposition behavior of adult females. However, insect larvae may move from the natal host and undermine the effectiveness of this approach. We investigated the longevity and feeding preference of pickleworm neonates (Diaphania nitidalis Cramer (Lepidoptera: Crambidae)) in relation to a potential push-pull cropping approach incorporating squash as a trap crop (pull) and watermelon as a deterrent intercrop (push) to protect a main crop of cantaloupe. Neonates could survive between 24 to 64 h without food, indicating they have some initial energy reserves to keep alive while in search of a suitable feeding site. To assess neonate feeding preferences, naive neonates were given the choice of five foods; leaves of squash, cantaloupe, watermelon, bean, and a pinto bean-based artificial diet. To assess if previous feeding experience influences neonate food source preference, neonates were allowed to feed on one of the five foods for 24 h and then given the same choice of the five food sources. The neonates, with or without previous feeding experience, did not appear to have a significant preference for any of the cucurbits: squash, cantaloupe, or watermelon, but they did prefer a cucurbit to the bean leaf or artificial diet. Feeding experience on one of these non-host foods made neonates more accepting of these food sources in the choice arena even when host plant food sources became available. It appears that neonate feeding preferences of pickleworm would neither hinder nor enhance the potential success of the proposed cucurbits to be used in a potential push pull cropping approach for pickleworm management. PMID- 27399781 TI - Intermediate Filaments as Organizers of Cellular Space: How They Affect Mitochondrial Structure and Function. AB - Intermediate filaments together with actin filaments and microtubules form the cytoskeleton, which is a complex and highly dynamic 3D network. Intermediate filaments are the major mechanical stress protectors but also affect cell growth, differentiation, signal transduction, and migration. Using intermediate filament mitochondrial crosstalk as a prominent example, this review emphasizes the importance of intermediate filaments as crucial organizers of cytoplasmic space to support these functions. We summarize observations in different mammalian cell types which demonstrate how intermediate filaments influence mitochondrial morphology, subcellular localization, and function through direct and indirect interactions and how perturbations of these interactions may lead to human diseases. PMID- 27399780 TI - A Perspective of Immunotherapy for Prostate Cancer. AB - In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa. PMID- 27399784 TI - Methodology for Evaluating the Insect Growth Regulator (IGR) Methoprene on Packaging Films. AB - The insect growth regulator methoprene can be mixed into the matrix used to comprise bags and other packaging materials. Different methodologies were utilized to evaluate the efficacy of different types of methoprene-treated packaging towards Tribolium castaneum (Herbst), the red flour beetle, and T. confusum Jacquelin duVal, the confused flour beetle, two common insect species that infest stored products. Tests were conducted by creating arenas in which larvae were exposed on the packaging surface along with a flour food source, and assessments were made on adults emerging from the exposed progeny. Tests were also done by exposing adults, again with a flour food source, removing the adults after one week, and assessing adult emergence of progeny from those parental adults. In tests with larvae exposed on methoprene-treated birdseed bags, the outside surface had more activity compared to the inside surface, especially on T. confusum. In other studies with different types of packaging materials, there was generally 100% inhibition of adult emergence of exposed larvae or of progeny adults when parental adults were exposed on the methoprene-treated packaging. The best technique for evaluation was to expose late-stage larvae as the test life stage. Results show the potential of using methoprene-treated packaging for bagged storage of processed grains and grain products. PMID- 27399785 TI - Recruitment of Factor H to the Streptococcus suis Cell Surface is Multifactorial. AB - Streptococcus suis is an important bacterial swine pathogen and a zoonotic agent. Recently, two surface proteins of S. suis, Fhb and Fhbp, have been described for their capacity to bind factor H-a soluble complement regulatory protein that protects host cells from complement-mediated damages. Results obtained in this study showed an important role of host factor H in the adhesion of S. suis to epithelial and endothelial cells. Both Fhb and Fhbp play, to a certain extent, a role in such increased factor H-dependent adhesion. The capsular polysaccharide (CPS) of S. suis, independently of the presence of its sialic acid moiety, was also shown to be involved in the recruitment of factor H. However, a triple mutant lacking Fhb, Fhbp and CPS was still able to recruit factor H resulting in the degradation of C3b in the presence of factor I. In the presence of complement factors, the double mutant lacking Fhb and Fhbp was similarly phagocytosed by human macrophages and killed by pig blood when compared to the wild-type strain. In conclusion, this study suggests that recruitment of factor H to the S. suis cell surface is multifactorial and redundant. PMID- 27399786 TI - What's Special about Human Imitation? A Comparison with Enculturated Apes. AB - What, if anything, is special about human imitation? An evaluation of enculturated apes' imitation skills, a "best case scenario" of non-human apes' imitation performance, reveals important similarities and differences between this special population of apes and human children. Candidates for shared imitation mechanisms include the ability to imitate various familiar transitive responses and object-object actions that involve familiar tools. Candidates for uniquely derived imitation mechanisms include: imitating novel transitive actions and novel tool-using responses as well as imitating opaque or intransitive gestures, regardless of familiarity. While the evidence demonstrates that enculturated apes outperform non-enculturated apes and perform more like human children, all apes, regardless of rearing history, generally excel at imitating familiar, over-rehearsed responses and are poor, relative to human children, at imitating novel, opaque or intransitive responses. Given the similarities between the sensory and motor systems of preschool age human children and non-human apes, it is unlikely that differences in sensory input and/or motor-output alone explain the observed discontinuities in imitation performance. The special rearing history of enculturated apes-including imitation-specific training further diminishes arguments suggesting that differences are experience dependent. Here, it is argued that such differences are best explained by distinct, specialized mechanisms that have evolved for copying rules and responses in particular content domains. Uniquely derived social and imitation learning mechanisms may represent adaptations for learning novel communicative gestures and complex tool-use. Given our species' dependence on both language and tools, mechanisms that accelerated learning in these domains are likely to have faced intense selective pressures, starting with the earliest of human ancestors. PMID- 27399788 TI - Impact of PAC Fines in Fouling of Polymeric and Ceramic Low-Pressure Membranes for Drinking Water Treatment. AB - This study assessed the issue of membrane fouling in a Hybrid Membrane Process (HMP) due to the export of powdered activated carbon (PAC) fines from a pretreatment contactor. Two parallel pilot-scale ceramic and polymeric membranes were studied. Reversible and irreversible foulings were measured following three cleaning procedures: Physical backwashing (BW), chemically enhanced backwashing (CEB) and Clean-in-Place (CIP). The impacts on fouling of membrane type, operation flux increase and the presence/absence of the PAC pretreatment were investigated. Membranes without pretreatment were operated in parallel as a control. In addition, CIP washwaters samples were analyzed to measure organic and inorganic foulants removed from the membranes. It was observed that for the polymeric membranes, fouling generally increased with the presence of the PAC pretreatment because of the export of fines. On the contrary, the ceramic membranes were not significantly impacted by their presence. The analysis of CIP washwaters showed a greater total organic carbon (TOC) content on membranes with a PAC pretreatment while no similar conclusion could be made for inorganic foulants. PMID- 27399787 TI - Protection against Radiotherapy-Induced Toxicity. AB - Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents. PMID- 27399789 TI - Synchrotron-Based in Situ Characterization of the Scaffold Mass Loss from Erosion Degradation. AB - The mass loss behavior of degradable tissue scaffolds is critical to their lifespan and other degradation-related properties including mechanical strength and mass transport characteristics. This paper presents a novel method based on synchrotron imaging to characterize the scaffold mass loss from erosion degradation in situ, or without the need of extracting scaffolds once implanted. Specifically, the surface-eroding degradation of scaffolds in a degrading medium was monitored in situ by synchrotron-based imaging; and the time-dependent geometry of scaffolds captured by images was then employed to estimate their mass loss with time, based on the mathematical model that was adopted from the literature of surface erosion with the experimentally-identified model parameters. Acceptable agreement between experimental results and model predictions was observed for scaffolds in a cylindrical shape, made from poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL). This study illustrates that geometry evaluation by synchrotron-based imaging is an effective means to in situ characterize the scaffold mass loss as well as possibly other degradation-related properties. PMID- 27399790 TI - Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies. AB - Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and BiacoreTM C1 sensor chips is achieved via Copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets-a must for the development of advanced miniaturized, multi-biomarker biosensor platforms. PMID- 27399791 TI - Phenotype as Agent for Epigenetic Inheritance. AB - The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID- 27399792 TI - Metabolomics: Bridging the Gap between Pharmaceutical Development and Population Health. AB - Metabolomics has emerged as an essential tool for studying metabolic processes, stratification of patients, as well as illuminating the fundamental metabolic alterations in disease onset, progression, or response to therapeutic intervention. Metabolomics materialized within the pharmaceutical industry as a standalone assay in toxicology and disease pathology and eventually evolved towards aiding in drug discovery and pre-clinical studies via supporting pharmacokinetic and pharmacodynamic characterization of a drug or a candidate. Recent progress in the field is illustrated by coining of the new term Pharmacometabolomics. Integration of data from metabolomics with large-scale omics along with clinical, molecular, environmental and behavioral analysis has demonstrated the enhanced utility of deconstructing the complexity of health, disease, and pharmaceutical intervention(s), which further highlight it as an essential component of systems medicine. This review presents the current state and trend of metabolomics applications in pharmaceutical development, and highlights the importance and potential of clinical metabolomics as an essential part of multi-omics protocols that are directed towards shaping precision medicine and population health. PMID- 27399794 TI - Cancer Center Advertising-Where Hope Meets Hype. PMID- 27399793 TI - Estimating Dengue Transmission Intensity from Case-Notification Data from Multiple Countries. AB - BACKGROUND: Despite being the most widely distributed mosquito-borne viral infection, estimates of dengue transmission intensity and associated burden remain ambiguous. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing the burden of disease and the likely impact of interventions. METHODOLOGY/PRINCIPLE FINDINGS: We estimated the force of infection (lambda) and corresponding basic reproduction numbers (R0) by fitting catalytic models to age stratified incidence data identified from the literature. We compared estimates derived from incidence and seroprevalence data and assessed the level of under reporting of dengue disease. In addition, we estimated the relative contribution of primary to quaternary infections to the observed burden of dengue disease incidence. The majority of R0 estimates ranged from one to five and the force of infection estimates from incidence data were consistent with those previously estimated from seroprevalence data. The baseline reporting rate (or the probability of detecting a secondary infection) was generally low (<25%) and varied within and between countries. CONCLUSIONS/SIGNIFICANCE: As expected, estimates varied widely across and within countries, highlighting the spatio temporally heterogeneous nature of dengue transmission. Although seroprevalence data provide the maximum information, the incidence models presented in this paper provide a method for estimating dengue transmission intensity from age stratified incidence data, which will be an important consideration in areas where seroprevalence data are not available. PMID- 27399795 TI - Testosterone Level in Testicular Cancer Patients after Chemotherapy. AB - Background: The use of chemotherapy for the treatment of cancer began at the start of the 20th century in an attempt to narrow the universe of chemicals that affect the disease. Metastatic testicular cancer has always been sensitive to chemotherapy. Subjects and Method: A retrospective and prospective study was performed of patients who had undergone testicular cancer from 2011-2013. The overall age of the testicular cancer patients at the time of diagnosis, their marital status, stage of disease and treatment strategies, testosterone level etc were analysed using linear regression and t-test. Results: Most of the patients had seminoma tumour. A greater number of patients were diagnosed in the later stages of the disease. Before chemotherapy, testosterone level was normal and decreased during chemotherapy but after completion, it returned to normal level. Conclusion: There is an early onset of testicular cancer in the Pakistani population. There is no effect of chemotherapy on testosterone production in late survivors. PMID- 27399797 TI - High blood pressure: prevalence and adherence to guidelines in a population-based cohort. AB - QUESTIONS UNDER STUDY: High blood pressure, the single leading health risk factor worldwide, contributes greatly to morbidity and mortality. This study aimed to add to the understanding of diagnosed and undiagnosed high blood pressure in Switzerland and to evaluate adherence to hypertension guidelines. METHODS: Included were 3962 participants from the first (2001-2003) and second (2010-2011) follow-ups of the population-based Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults. High blood pressure was defined as blood pressure >=140/90 mm Hg and the prevalence of doctor-diagnosed hypertension was based on questionnaire information. RESULTS: High blood pressure was found in 34.9% of subjects, 49.1% of whom were unaware of this condition; 30.0% had doctor diagnosed hypertension and, although 82.1% of these received drug treatments, in only 40.8% was blood pressure controlled (<140/90 mm Hg). Substantial first-line beta-blocker use and nonadherence to comorbidity-specific prescription guidelines were observed and remained mostly unexplained. Age-adjusted rates of unawareness and uncontrolled hypertension were more than 20% higher than in the USA. CONCLUSIONS: There is room for improvement in managing hypertension in Switzerland. Population-based observational studies are essential for identifying and evaluating unmet needs in healthcare; however, to pinpoint the underlying causes it is imperative to facilitate linkage of cohort data to medical records. PMID- 27399799 TI - Microsurgical posterior cervical foraminotomy: a study of 181 cases. AB - BACKGROUND: An unsettled controversy over the appropriate surgical approach in cases of cervical radiculopathy caused by degenerative vertebrae and intervertebral discs is still present. The purpose of this study is to examine the efficacy of microsurgical posterior foraminotomy in the treatment of cervical radiculopathy and to find out whether the underlying pathology (soft disc herniation/spondylosis) is of value in predicting long-term outcome after this procedure. METHODS: Patients, who underwent posterior cervical foraminotomy (PCF) at our department between 2006 and 2013 for unilateral mono-segmental lateral soft disc herniation, or spondylosis, or both, were enrolled in this study. Demographic, clinical and surgical data were retrospectively reviewed. The patients were subsequently interviewed by telephone to identify their long-term outcome. The clinical outcomes were evaluated using Odom's criteria. Descriptive statistics were frequencies and percentage of occurrence for categorical variables and mean and range for continuous variables. RESULTS: One hundred eighty-one patients were included in this study, with a median follow-up of 58 months (mean 43 months, range 12-96 months). The overall re-operation rate was 7.2% (13 patients); 11 patients (6%) for recurrent root symptoms due to recurrent disc herniation (six patients, 3.3%) and re-stenosis (five patients, 2.8%), one patient (0.55%) for wound infection and one patient (0.55%) for postoperative haematoma. Among the eleven patients who underwent re-operation for recurrent root symptoms there was one patient who additionally had persistent cerebrospinal fluid leak and superficial posterior wound infection. There was no significant difference between lateral soft disc herniation and spondylosis in term of re operation rate. At discharge, excellent or good outcome was achieved in 89% of patients; the long-term success rate was 97.2% using Odom's criteria. CONCLUSION: Microsurgical PCF is an effective technique for treating lateral spinal root compression. Proper patient selection is obligatory to achieve the best results. PMID- 27399802 TI - Study on the bias-dependent effects of proton-induced damage in CdZnTe radiation detectors using ion beam induced charge microscopy. AB - The influence of damage induced by 2MeV protons on CdZnTe radiation detectors is investigated using ion beam induced charge (IBIC) microscopy. Charge collection efficiency (CCE) in irradiated region is found to be degraded above a fluence of 3.3*10(11)p/cm(2) and the energy spectrum is severely deteriorated with increasing fluence. Moreover, CCE maps obtained under the applied biases from 50V to 400V suggests that local radiation damage results in significant degradation of CCE uniformity, especially under low bias, i. e., 50V and 100V. The CCE nonuniformity induced by local radiation damage, however, can be greatly improved by increasing the detector applied bias. This bias-dependent effect of 2MeV proton-induced radiation damage in CdZnTe detectors is attributed to the interaction of electron cloud and radiation-induced displacement defects. PMID- 27399803 TI - An International Survey of Brain Banking Operation and Characterization Practices. AB - Brain banks continue to make a major contribution to the study of neurological and psychiatric disorders. The current complexity and scope of research heighten the need for well-characterized cases and the demand for larger cohorts and necessitate strategies, such as the establishment of bank networks based in regional areas. While individual brain banks have developed protocols that meet researchers' needs within the confines of resources and funding, to further promote collaboration, standardization and scientific validity and understanding of the current protocols of participating banks are required. A survey was sent to brain banks, identified by an Internet search, to investigate operational protocols, case characterization, cohort management, data collection, standardization, and degree of collaboration between banks. The majority of the 24 banks that returned the survey have been established for more than 20 years, and most are affiliated with a regional network. While prospective donor programs were the primary source of donation, the data collected on donors varied. Longitudinal information assists case characterization and enhances the analysis capabilities of research. However, acquiring this information depended on the availability of qualified staff. Respondents indicated a high level of importance for standardization, but only 8 of 24 considered this occurred between banks. Standard diagnostic criteria were not achieved in the classification of controls, and some banks relied on the researcher to indicate the criteria for classification of controls. Although the capacity to collaborate with other banks was indicated by 16 of 24 banks, this occurred infrequently. Engagement of all brain banks to participate toward a consensus of diagnostic tools, especially for controls, will strengthen collaboration. PMID- 27399804 TI - Evaluation of mRNA Localization Using Double Barrel Scanning Ion Conductance Microscopy. AB - Information regarding spatial mRNA localization in single cells is necessary for a better understanding of cellular functions in tissues. Here, we report a method for evaluating localization of mRNA in single cells using double-barrel scanning ion conductance microscopy (SICM). Two barrels in a nanopipette were filled with aqueous and organic electrolyte solutions and used for SICM and as an electrochemical syringe, respectively. We confirmed that the organic phase barrel could be used to collect cytosol from living cells, which is a minute but sufficient amount to assess cellular status using qPCR analysis. The water phase barrel could be used for SICM to image topography with subcellular resolution, which could be used to determine positions for analyzing mRNA expression. This system was able to evaluate mRNA localization in single cells. After puncturing the cellular membrane in a minimally invasive manner, using SICM imaging as a guide, we collected a small amount cytosol from different positions within a single cell and showed that mRNA expression depends on cellular position. In this study, we show that SICM imaging can be utilized for the analysis of mRNA localization in single cells. In addition, we fully automated the pipet movement in the XYZ-directions during the puncturing processes, making it applicable as a high-throughput system for collecting cytosol and analyzing mRNA localization. PMID- 27399805 TI - The Puzzle of Huntington Disease Phenocopies. PMID- 27399806 TI - AMA0428, A Potent Rock Inhibitor, Attenuates Early and Late Experimental Diabetic Retinopathy. AB - PURPOSE: Diabetic retinopathy (DR) is characterized by an early stage of inflammation and vessel leakage, and an advanced vasoproliferative stage. Also, neurodegeneration might play an important role in disease pathogenesis. The aim of this study was to investigate the effect of the Rho kinase (ROCK) inhibitor, AMA0428, on these processes. METHODS: The response to ROCK inhibition by AMA0428 (1 ug) was studied in vivo using the murine model for streptozotocin (STZ) induced diabetes, focusing on early non-proliferative DR features and the oxygen induced retinopathy (OIR) model to investigate proliferative DR. Intravitreal (IVT) administration of AMA0428 was compared with murine anti-VEGF-R2 antibody (DC101, 6.2 ug) and placebo (H2O/PEG; 1C8). Outcome was assessed by analyzing leukostasis using fluorescein isothiocyanate coupled concanavalin A (FITC-ConA) and vessel leakage (bovine serum albumin conjugated with fluorescein isothiocyanate; FITC-BSA)/neovascularization and neurodegeneration by immunohistological approaches (hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), Brn3a). ELISA and Western blotting were employed to unravel the consequences of ROCK inhibition (1 uM AMA0428) on myosin phosphatase target protein (MYPT)-1 phosphorylation, endothelial nitric oxide synthase (eNOS) phosphorylation, and vascular endothelial growth factor (VEGF) levels in retinas of diabetic mice, on NF-kappabeta activity and ICAM-1 expression in endothelial cells (ECs). RESULTS: In vivo, AMA0428 significantly reduced vessel leakage and neovascularization, respectively, in the STZ and OIR model, comparable to DC101 therapy. Additionally, the ROCK inhibitor decreased neurodegeneration in both models and inhibited leukostasis by 30% (p < 0.05) in the STZ model (p < 0.05), while DC101 had no positive effect on the outcome of these latter processes. ROCK activity was upregulated in the diabetic retina and AMA0428 administration resulted in decreased phospho-MYPT-1, enhanced phospho-eNOS, and reduced VEGF levels. In vitro, AMA0428 interfered with NF-kappabeta activity, thereby inhibiting ICAM-1 expression in ECs. CONCLUSIONS: Targeting ROCK with AMA0428 effectively attenuated outcome in an early DR model (STZ) and a late vasoproliferative retinopathy model (OIR). These findings make AMA0428 a promising candidate with an additional anti-inflammatory and neuroprotective benefit for DR patients, as compared with anti-VEGF treatment. PMID- 27399808 TI - The clinicopathologic significance of estrogen receptors in human gastric carcinoma. AB - In most populations, gastric cancer (GC) is approximately two times more prevalent in men than in women, which may suggest the protective role of sex steroid hormones in gastric carcinogenesis. Steroid hormones such as androgens and estrogens can be synthesized not only in the gonads but also in peripheral tissues. Many researchers have conducted studies examining the expression profile of enzymes involved in steroid synthesis, the occurrence of estrogen receptors (ERs) and the influence of ERs in the development, proliferation and progression of gastric cancer. Some studies have also evaluated the relationship between the presence of ERs and survival prognosis. However, the results of these studies are often controversial and divergent. In a recent study, it was indicated that sex steroid hormones and estrogen receptors are partly involved in gastric cancer but their clinicopathological significance still needs further investigation. PMID- 27399807 TI - The combination of bleomycin with suicide or interferon-beta gene transfer is able to efficiently eliminate human melanoma tumor initiating cells. AB - We explored the potential of a chemogene therapy combination to eradicate melanoma tumor initiating cells, key producers of recurrence and metastatic spread. Three new human melanoma cell lines, two obtained from lymph nodes and one from spleen metastasis were established and characterized. They were cultured as monolayers and spheroids and, in both spatial configurations they displayed sensitivity to single treatments with bleomycin (BLM) or human interferon-beta (hIFNbeta) gene or herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) lipofection. However, the combination of bleomycin with SG or hIFNbeta gene transfer displayed greater antitumor efficacy. The three cell lines exhibited a proliferative behavior consistent with melan A and gp100 melanoma antigens expression, and BRAF V600E mutation. BLM and both genetic treatments increased the fraction of more differentiated and treatment-sensitive cells. Simultaneously, they significantly decreased the sub-population of tumor initiating cells. There was a significant correlation between the cytotoxicity of treatments with BLM and gene transfer and the fraction of cells exhibiting (i) high proliferation index, and (ii) high intracellular levels of reactive oxygen species. Conversely, the fraction of cells surviving to our treatments closely paralleled their (i) colony and (ii) melanosphere forming capacity. A very significant finding was that the combination of BLM with SG or hIFNbeta gene almost abrogated the clonogenic capacity of the surviving cells. Altogether, the results presented here suggest that the combined chemo-gene treatments are able to eradicate tumor initiating cells, encouraging further studies aimed to apply this strategy in the clinic. PMID- 27399809 TI - Activity of pyrrolizidine alkaloids against biofilm formation and Trichomonas vaginalis. AB - Crotalaria genus belongs to the subfamily Papilionoideae comprising about 600 species spread throughout tropical, neotropical and subtropical regions. In this study, seeds of Crolatalaria pallida were used to the isolation of usaramine, a pyrrolizidine alkaloid. Thus, Pseudomonas aeruginosa and Staphylococcus epidermidis were utilized as strains to test some activities of this alkaloid, such as antibiofilm and antibacterial. Meanwhile, monocrotaline obtained from Crotalaria retusa seeds, was used as the starting material for synthesis of necine base derivatives with anti-Trichomonas vaginalis potential. Alkaloids were characterized by 1D and 2D NMR techniques and GC-MS analysis. Usaramine demonstrated a highlighted antibiofilm activity against S. epidermidis by reducing more than 50% of biofilm formation without killing the bacteria, thus it could be assumed as a prototype for the development of new antibiofilm molecules for pharmaceutical and industrial purposes. Monocrotaline activity against T. vaginalis was evaluated and results indicated inhibition of 80% on parasite growth at 1mg/mL, in addition, neither cytotoxicity against vaginal epithelial cells nor hemolytic activity were observed. On the other hand, retronecine showed no anti-T. vaginalis activity while azido-retronecine was more active than monocrotaline killing 85% of the parasites at 1mg/mL. In conclusion, pyrrolizidine alkaloids are suggested as promising prototypes for new drugs especially for topical use. PMID- 27399810 TI - Amlodipine and atorvastatin improve ventricular hypertrophy and diastolic function via inhibiting TNF-alpha, IL-1beta and NF-kappaB inflammatory cytokine networks in elderly spontaneously hypertensive rats. AB - This study aimed to examine the effects of amlodipine and atorvastatin alone or in combination on the regulation of inflammatory cytokines and the underlying mechanisms in elderly spontaneously hypertensive (SH) rats. The level of serum hs CRP was detected with ELISA. The serum TNF-alpha and IL-1beta levels were assessed by radioimmunity assay (RIA). Cardiac inflammatory cell infiltration was observed by HE staining. The protein levels of TNF-alpha, IL-1beta, of NF-kappaB P65 and IkappaBalpha were detected by immunoblotting. The intracellular localization of NF-kappaB p65 was observed using immunohistochemistry. Amlodipine or atorvastatin obviously ameliorated the myocardial inflammatory cell infiltration in SH rats, which was further improved by combinatorial treatment with amlodipine and atorvastatin. Either amlodipine or atorvastatin decreased plasma IL-1beta content in SH rats, but there was no significant difference when compared with untreated SH rats. However, the combination of amlodipine and atorvastatin significantly decreased plasma IL-1beta level in SH rats. Moreover, amlodipine or atorvastatin intervention significantly reduced myocardial TNF alpha and IL-1beta protein levels in SH rats, which was further suppressed by the combination of amlodipine and atorvastatin. In addition, amlodipine or atorvastatin inhibited the activity of NF-kappaB signaling in SH rats, which was further suppressed by combinatorial treatment. Furthermore, amlodipine or atorvastatin restored the activity of IkappaB-alpha in SH rats, which was enhanced by combinatorial treatment. Our results demonstrated amlodipine and atorvastatin improved ventricular hypertrophy and diastolic function possibly through the intervention of TNF-alpha, IL-1beta, NF-kappaB/IkappaB inflammatory cytokine network. Our study suggests that amlodipine combined with atorvastatin may have additive effect on inhibiting inflammatory response. PMID- 27399811 TI - Roles of monoaminergic, antioxidant defense and neuroendocrine systems in antidepressant-like effect of Cnestis ferruginea Vahl ex DC (Connaraceae) in rats. AB - We have earlier reported antidepressant-like effect of Cnestis ferruginea and its bioflavonoid constituent, amentoflavone in behavioural paradigms but its effects on neurochemical and neuroendocrine systems are yet to be elucidated. This study sought to investigate the effect of subchronic treatment of C. ferruginea (CF) on monoamines system, hypothalamo-pituitary adrenal axis and nitrosative/oxidative stresses. Male albino rats (150-200g) randomly divided into seven groups; Group I: vehicle treated (0.2%v/v Tween 80 in normal saline (10ml/kg; p.o.; unstressed), Group II: vehicle treated+restraint stress, Group III: imipramine (20mg/kg; p.o.), Group IV-VI: CF (12.5, 50, or 100mg/kg; p.o., respectively), Group VII: CF 6.25+imipramine 5mg/kg. One hour post-treatment, animals were subjected to 20min restraint stress and 6min, forced swim test (FST) for a period of 14 days. CF (12.5, 50 and 100mg/kg) produced significant reduction in immobility time and an increase in climbing behaviour. CF attenuated repeated restraint stress*FST-induced serum corticosterone [F(6,28)=5.45,P<0.01]. Exposure of rats to FST+restraint stress paradigms produced significant (P<0.05) increase in malondialdehyde and nitrite level, also reduced the glutathione level and superoxide dismutase activity which was reversed by subchronic treatment of rats with CF. Restraint stress*FST significantly decreased NA, DA and 5-HT concentrations, with increased DA and 5-HT turnover ratios in discrete brain regions which was ameliorated by CF or imipramine subchronic treatment. These results suggest that the antidepressant-like effect of C. ferruginea involved enhancement of monoamines and antioxidant as well as normalization of neuroendocrine systems. PMID- 27399812 TI - SweetNET: A Bioinformatics Workflow for Glycopeptide MS/MS Spectral Analysis. AB - Glycoproteomics has rapidly become an independent analytical platform bridging the fields of glycomics and proteomics to address site-specific protein glycosylation and its impact in biology. Current glycopeptide characterization relies on time-consuming manual interpretations and demands high levels of personal expertise. Efficient data interpretation constitutes one of the major challenges to be overcome before true high-throughput glycopeptide analysis can be achieved. The development of new glyco-related bioinformatics tools is thus of crucial importance to fulfill this goal. Here we present SweetNET: a data oriented bioinformatics workflow for efficient analysis of hundreds of thousands of glycopeptide MS/MS-spectra. We have analyzed MS data sets from two separate glycopeptide enrichment protocols targeting sialylated glycopeptides and chondroitin sulfate linkage region glycopeptides, respectively. Molecular networking was performed to organize the glycopeptide MS/MS data based on spectral similarities. The combination of spectral clustering, oxonium ion intensity profiles, and precursor ion m/z shift distributions provided typical signatures for the initial assignment of different N-, O- and CS-glycopeptide classes and their respective glycoforms. These signatures were further used to guide database searches leading to the identification and validation of a large number of glycopeptide variants including novel deoxyhexose (fucose) modifications in the linkage region of chondroitin sulfate proteoglycans. PMID- 27399813 TI - Predicting Arsenic in Drinking Water Wells of the Central Valley, California. AB - Probabilities of arsenic in groundwater at depths used for domestic and public supply in the Central Valley of California are predicted using weak-learner ensemble models (boosted regression trees, BRT) and more traditional linear models (logistic regression, LR). Both methods captured major processes that affect arsenic concentrations, such as the chemical evolution of groundwater, redox differences, and the influence of aquifer geochemistry. Inferred flow-path length was the most important variable but near-surface-aquifer geochemical data also were significant. A unique feature of this study was that previously predicted nitrate concentrations in three dimensions were themselves predictive of arsenic and indicated an important redox effect at >10 MUg/L, indicating low arsenic where nitrate was high. Additionally, a variable representing three dimensional aquifer texture from the Central Valley Hydrologic Model was an important predictor, indicating high arsenic associated with fine-grained aquifer sediment. BRT outperformed LR at the 5 MUg/L threshold in all five predictive performance measures and at 10 MUg/L in four out of five measures. BRT yielded higher prediction sensitivity (39%) than LR (18%) at the 10 MUg/L threshold-a useful outcome because a major objective of the modeling was to improve our ability to predict high arsenic areas. PMID- 27399814 TI - ACSM Clinician Profile. PMID- 27399815 TI - Venous Thromboembolism in Athletes: Lessons from the Chris Bosh Story. PMID- 27399817 TI - Exercise During Pregnancy. PMID- 27399818 TI - Spontaneous Osteonecrosis of the Knee. PMID- 27399819 TI - Minds Matter: Concussion Care for Children. PMID- 27399820 TI - Recent Developments in the Use of Sodium Bicarbonate as an Ergogenic Aid. AB - This review examines the current status of sodium bicarbonate as an ergogenic aid. It builds on previous reviews in the area. Current research would suggest that as an ergogenic aid, a 300 mg.kg dose of NaHCO3 can improve high-intensity exercise, within a range of exercise modalities, such as a single bout of supramaximal exercise, high-intensity intermittent activity, and skill-based sports. In particular, these benefits seem to be present to a greater extent within trained individuals. Despite this, there appears to exist a high intraindividual variability in response to NaHCO3, and therefore, the ergogenic benefits may not be induced during every exercise bout. Current thinking also suggests that athletes need to individualize their ingestion timings to maximize peak pH or blood bicarbonate to effectively maximize the performance effect, and this may allow individuals to attain the ergogenic benefits of NaHCO3 more consistently. PMID- 27399821 TI - High-Intensity Intermittent Exercise: Effect on Young People's Cardiometabolic Health and Cognition. AB - With only a quarter of young people currently meeting physical activity guidelines, two key areas of concern are the effects of exercise on cardiometabolic health and cognition. Despite the fact that physical activity in young people is typically high intensity and intermittent in nature, much of the literature examines traditional endurance-type exercise. This review provides an update on the effects of high-intensity intermittent exercise on young people's cardiometabolic health and cognition. High-intensity intermittent exercise has acute beneficial effects on endothelial function and postprandial lipemia and chronic positive effects on weight management. In addition, there is emerging evidence regarding chronic benefits on the blood lipid profile, blood pressure, and proinflammatory and anti-inflammatory cytokines. Furthermore, emerging evidence suggests beneficial acute and chronic effects of high-intensity intermittent exercise on cognition. However, further research is required in both cardiometabolic health and cognition, particularly regarding the impact of school based interventions in adolescents. PMID- 27399822 TI - Nutrition and Supplements for Elite Open-Weight Rowing. AB - Competitive rowing events are raced over 2,000 m requiring athletes to have highly developed aerobic and anaerobic systems. Elite rowers therefore undertake training sessions focused on lactate tolerance, strength and power as well as aerobic and anaerobic capacity development, that can amount to a 24-h training week. The training stimuli and consequent metabolic demands of each session in a rowing training program differ depending on type, length, and intensity. Nutrition guidelines for endurance- and power-based sports should be drawn upon; however, individualized and flexible nutrition plans are critical to successfully meet the daily, weekly, and cyclic nutrient requirements of a rower. This review will provide an overview of key nutritional strategies to optimize training and enhance adaptation, and briefly discuss supplement strategies that may support health and enhance performance in elite rowing. PMID- 27399823 TI - Commercial Hype Versus Reality: Our Current Scientific Understanding of Gluten and Athletic Performance. AB - Recent explosion in the prevalence of gluten-free athletes, exacerbated by unsubstantiated commercial health claims, has led to some professional athletes touting gluten-free diet as the secret to their success. Forty-one percent of athletes report adhering to a gluten-free diet (GFD), which is four-fold higher than the population-based clinical requirements. Many nonceliac athletes believe that gluten avoidance improves gastrointestinal well-being, reduces inflammation, and provides an ergogenic edge, despite the fact that limited data yet exist to support any of these benefits. There are several plausible associations between endurance-based exercise and gastrointestinal permeability whereby a GFD may be beneficial. However, the implications of confounding factors, including the risks of unnecessary dietary restriction, financial burden, food availability, psychosocial implications, alterations in short-chain carbohydrates (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), and other wheat constituents emphasize the need for further evaluation. PMID- 27399824 TI - Intradialytic Exercise is Medicine for Hemodialysis Patients. AB - When a person's kidneys fail, hemodialysis (HD) is the most common treatment modality. With a growing number of patients requiring this life-sustaining treatment, and with evidence illustrating the significant physical dysfunction of this population, encouraging exercise is essential. The use of intradialytic exercise, as a novel and efficient use of time during HD, is well established in Australia and some European nations; however, it is slower to start in North America. While a large number of small studies have demonstrated numerous benefits and safe delivery of intradialytic exercise training for patients with end-stage kidney disease, intradialytic exercise is rarely delivered as standard of care. It is of utmost importance for health care staff to overcome barriers and bring theory into practice. Included in this report are current recommendations from governing bodies, expert opinion, as well as established policies and procedures from a successful intradialytic exercise program in Canada. PMID- 27399825 TI - From a Vital Sign to Vitality: Selling Exercise So Patients Want to Buy It. AB - Exercise is Medicine (EIM) and physical activity as a vital sign are based on health-focused research and reflect ideal frames and messages for clinicians. However, they are nonoptimal for patients because they do not address what drives patients' decision-making and motivation. With the growing national emphasis on patient-centered and value-based care, it is the perfect time for EIM to evolve and advance a second-level consumer-oriented exercise prescription and communication strategy. Through research on decision-making, motivation, consumer behavior, and meaningful goal pursuit, this article features six evidence-based issues to help clinicians make physical activity more relevant and compelling for patients to sustain in ways that concurrently support patient-centered care. Physical activity prescriptions and counseling can evolve to reflect affective and behavioral science and sell exercise so patients want to buy it. PMID- 27399826 TI - The Impact of Fitness on Surgical Outcomes: The Case for Prehabilitation. AB - In recent years, a growing body of research has demonstrated that an individual's fitness level is a strong and independent marker of risk for cardiovascular and all-cause mortality. In addition, modest improvements in fitness through exercise intervention have been associated with considerable health outcome benefits. These studies have generally assessed fitness as a baseline marker in traditional epidemiological cohorts. However, there has been a recent recognition that fitness powerfully predicts outcomes associated with a wide range of surgical interventions. The concept of 'prehabilitation' is based on the principle that patients with higher functional capability will better tolerate a surgical intervention, and studies have shown that patients with higher fitness have reduced postoperative complications and demonstrate better functional, psychosocial, and surgery-related outcomes. This review focuses on the impact of fitness on surgical outcomes and provides a rationale in support of routine application of prehabilitation in the management of patients undergoing surgery. PMID- 27399828 TI - Zika and Rio Olympic Games. AB - Zika virus (ZIKV) is an arthropod-borne virus that is mainly transmitted via a bite from a female mosquito of the Aedes species. However, ZIKV can be transmitted sexually or via blood. Due to the recent ZIKV outbreak in South and Central America, many national and international organizations are concerned about the safety of athletes, coaches, staff, and spectators during the Olympic and Paralympic Games. Infected individuals are generally asymptomatic or have mild symptoms. However, ZIKV infection can potentially cause serious complications such as Guillain-Barre syndrome and congenital defects. Preferred diagnosis is based on real-time reverse-transcription polymerase chain reaction from blood and urine. Currently, there is no treatment or immunization available for ZIKV infection, and disease control is limited to preventing mosquito bites. PMID- 27399827 TI - Promoting Physical Activity among Underserved Populations. AB - Underserved populations, including racial/ethnic minorities, individuals with low socioeconomic status, and individuals with physical disabilities, are less likely to engage in sufficient moderate to vigorous physical activity (MVPA) and are thus at increased risk of morbidity and mortality. These populations face unique challenges to engaging in MVPA. Learning how to overcome these challenges is a necessary first step in achieving health equity through health promotion research. In this review of the literature, we discuss issues and strategies that have been used to promote MVPA among individuals from underserved populations, focusing on recruitment, intervention delivery, and the use of technology in interventions. Physical activity promotion research among these vulnerable populations is scarce. Nevertheless, there is preliminary evidence of efficacy in the use of certain recruitment and intervention strategies including tailoring, cultural adaptation, incorporation of new technologies, and multilevel and community-based approaches for physical activity promotion among different underserved populations. PMID- 27399829 TI - The role of training structure in perceptual learning of accented speech. AB - Foreign-accented speech contains multiple sources of variation that listeners learn to accommodate. Extending previous findings showing that exposure to high variation training facilitates perceptual learning of accented speech, the current study examines to what extent the structure of training materials affects learning. During training, native adult speakers of American English transcribed sentences spoken in English by native Spanish-speaking adults. In Experiment 1, training stimuli were blocked by speaker, sentence, or randomized with respect to speaker and sentence (Variable training). At test, listeners transcribed novel English sentences produced by unfamiliar Spanish-accented speakers. Listeners' transcription accuracy was highest in the Variable condition, suggesting that varying both speaker identity and sentence across training trials enabled listeners to generalize their learning to novel speakers and linguistic content. Experiment 2 assessed the extent to which ordering of training tokens by a single factor, speaker intelligibility, would facilitate speaker-independent accent learning, finding that listeners' test performance did not reliably differ from that in the no-training control condition. Overall, these results suggest that the structure of training exposure, specifically trial-to-trial variation on both speaker's voice and linguistic content, facilitates learning of the systematic properties of accented speech. The current findings suggest a crucial role of training structure in optimizing perceptual learning. Beyond characterizing the types of variation listeners encode in their representations of spoken utterances, theories of spoken language processing should incorporate the role of training structure in learning lawful variation in speech. (PsycINFO Database Record PMID- 27399830 TI - Optic flow speed modulates guidance level control: New insights into two-level steering. AB - Responding to changes in the road ahead is essential for successful driving. Steering control can be modeled using 2 complementary mechanisms: guidance control (to anticipate future steering requirements) and compensatory control (to stabilize position-in-lane). Drivers seem to rapidly sample the visual information needed for steering using active gaze patterns, but the way in which this perceptual information is combined remains unclear. Influential models of steering capture many steering behaviors using just 'far' and 'near' road regions to inform guidance and compensatory control respectively (Salvucci & Gray, 2004). However, optic flow can influence steering even when road-edges are visible (Kountouriotis, Mole, Merat, & Wilkie, 2016). Two experiments assessed whether flow selectively interacted with compensatory and/or guidance levels of steering control, under either unconstrained gaze or constrained gaze conditions. Optic flow speed was manipulated independent of the veridical road-edges so that use of flow would lead to predictable understeering or oversteering. Steering was found to systematically vary according to flow speed, but crucially the Flow-Induced Steering Bias (FISB) magnitude depended on which road-edge components were visible. The presence of a guidance signal increased the influence of flow, with the largest FISB in 'Far' and 'Complete' road conditions, whereas the smallest FISB was observed when only 'Near' road-edges were visible. Gaze behaviors influenced steering to some degree, but did not fully explain the interaction between flow and road-edges. Overall the experiments demonstrate that optic flow can act indirectly upon steering control by modulating the guidance signal provided by a demarcated path. (PsycINFO Database Record PMID- 27399831 TI - Broad attention to multiple individual objects may facilitate change detection with complex auditory scenes. AB - Attention and other processing constraints limit the perception of objects in complex scenes, which has been studied extensively in the visual sense. We used a change deafness paradigm to examine how attention to particular objects helps and hurts the ability to notice changes within complex auditory scenes. In a counterbalanced design, we examined how cueing attention to particular objects affected performance in an auditory change-detection task through the use of valid or invalid cues and trials without cues (Experiment 1). We further examined how successful encoding predicted change-detection performance using an object encoding task and we addressed whether performing the object-encoding task along with the change-detection task affected performance overall (Experiment 2). Participants had more error for invalid compared to valid and uncued trials, but this effect was reduced in Experiment 2 compared to Experiment 1. When the object encoding task was present, listeners who completed the uncued condition first had less overall error than those who completed the cued condition first. All participants showed less change deafness when they successfully encoded change relevant compared to irrelevant objects during valid and uncued trials. However, only participants who completed the uncued condition first also showed this effect during invalid cue trials, suggesting a broader scope of attention. These findings provide converging evidence that attention to change-relevant objects is crucial for successful detection of acoustic changes and that encouraging broad attention to multiple objects is the best way to reduce change deafness. (PsycINFO Database Record PMID- 27399832 TI - Phytoecdysteroids-containing extract from Stachys hissarica plant and its wound healing activity. AB - A number of phytoecdysteroid compounds, such as ecdysterone, polipodin V, 2-deoxy 20-hydroxyecdysone, integristeron A and 2-deoxydizon were isolated from Stachys hissarica plant and their structures were confirmed by NMR, mass and IR spectroscopy. In addition, the biological activity of the S. hissarica plant's extract was tested on rats for wound healing activity. It was shown that the extract at repeated oral (per os) administration at a dose of 10 mg/kg speeds up the healing process of linear skin wounds in rats. The wound-healing activity of S. hissarica extract is confirmed to be effective and exceeds known drug methyluracil (2,4-dioxo-6-methyl-1,2,3,4-tetrahydropyrimidine), especially in case of alloxan induced diabetic animals. PMID- 27399833 TI - Editorial Comment. PMID- 27399834 TI - Simulated Permeation and Characterization of PEGylated Gold Nanoparticles in a Lipid Bilayer System. AB - PEGylated gold nanoparticles are considered suitable nanocarriers for use in biomedical applications and targeted drug delivery systems. In our previous investigation with the alkanethiol-functionalized gold nanoparticle, we found that permeation across a protein-free phospholipid membrane resulted in damaging effects of lipid displacement and water and ion leakage. In the present study, we carry out a series of coarse-grained molecular simulations to explore permeation of lipid bilayer systems by a PEGylated gold nanoparticle, especially at the bulk liquid-lipid interface as well as the interface between the two lipid leaflets. Initially, we examine molecular-level details of a PEGylated gold nanoparticle (constructed from cycled annealing) in water and find a distribution of ligand configurations (from mushroom to brush states) present in nanoparticles with medium to high surface coverage. We also find that the characteristic properties of the PEGylated gold nanoparticle do not change when it is placed in a salt solution. In our permeation studies, we investigate events of water and ion penetration as well as lipid translocation while varying the ligand length, nanoparticle surface coverage, and ion concentration gradient of our system. Results from our studies show the following: (1) The number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with PEGn-SH surface coverage, ligand length, and permeation velocity but is not sensitive to the ion concentration gradient. (2) Lipid molecules do not leave the membrane; instead they complete trans-bilayer lipid flip-flop with longer ligands and higher surface coverages. (3) The lack of formation of stable water pores prevents ion translocation. (4) The PEGylated nanoparticle causes less damage to the membrane overall due to favorable interactions with the lipid headgroups which may explain why experimentalists observe endocytosis of PEGylated nanocarriers in vivo. PMID- 27399835 TI - Synthesis of Unnatural 2-Substituted Quinolones and 1,3-Diketones by a Member of Type III Polyketide Synthases from Huperzia serrata. AB - A curcuminoids, benzalacetone-, and quinolone-producing type III polyketide synthase (HsPKS3) from Huperzia serrata uniquely catalyzes the formation of unnatural 2-substituted quinolones and 1,3-diketones via head-to-head condensation of two completely different substrates. The broad range of substrate tolerance of HsPKS3 facilitates accessing structurally diverse 2-substituted quinolones and 1,3-diketones. PMID- 27399836 TI - Ultrasound-assisted prompted voiding for management of urinary incontinence of nursing home residents: Efficacy and feasibility. AB - OBJECTIVES: To assess the efficacy and feasibility of ultrasound-assisted prompted voiding for the management of urinary incontinence in nursing homes. METHODS: Nursing home residents who had received prompted voiding care for urinary incontinence were enrolled. The voided urinary volume and residual urinary volume were initially measured for a few days. The sum of the mean values of these volumes was considered as the optimal intravesical urinary volume for voiding. Thereafter, the participants underwent regular monitoring of intravesical urinary volume using an ultrasound device, and were prompted to void in a toilet when the monitored volume almost reached the optimal volume. The primary outcome for efficacy was the change in the absorbent cost before and after ultrasound-assisted prompted voiding care over 12 weeks. The feasibility was assessed by the change in activity of daily living of residents and quality of life measures of the care workers. RESULTS: A total of 77 residents completed the 12-week ultrasound-assisted prompted voiding intervention. The absorbent cost decreased in 40 participants (51.9%), and the overall cost decreased by 11.8% from the baseline value (P = 0.006). The activity of daily living did not significantly change. The quality of life of the care workers significantly improved for subscales of role emotional (P = 0.020) and mental health (P = 0.007). CONCLUSIONS: The management of urinary incontinence for nursing homes residents through ultrasound-assisted prompted voiding seems to reduce the absorbent cost and to partially improve care workers' quality of life. PMID- 27399838 TI - B4H4 and B4(CH3)4 as Unique Electron Donors in Hydrogen-Bonded and Halogen-Bonded Complexes. AB - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out on B4H4 and B4(CH3)4 to investigate the base properties of these molecules with Td symmetry. Each face of the tetrahedral structure of B4H4 and B4(CH3)4 is stabilized by a two-electron, three-center B-B-B bond. The face uses these two electrons to act uniquely as an electron-pair donor for the formation of stable hydrogen-bonded and halogen-bonded complexes with C3v symmetry. The hydrogen-bonded complexes are B4H4:HY and B4(CH3)4:HY, with HY = HNC, HF, HCl, HCN, and HCCH; the halogen bonded complexes are B4H4:ClY and B4(CH3)4:ClY, with ClY = ClF, ClCl, ClNC, ClCN, ClCCH, and ClH. The absolute values of the binding energies of the hydrogen bonded complexes B4(CH3)4:HY and of the halogen-bonded complexes B4(CH3)4:ClY are significantly greater than the binding energies of the corresponding complexes with B4H4. The binding energies of each series correlate with the distance from the hydrogen-bonded H atom or halogen-bonded Cl atom to the centroid of the interacting face. Charge transfer stabilizes all complexes and occurs from the B2 B3-B4 orbital of the face to the antibonding H-X orbital of HY in hydrogen-bonded complexes and to the antibonding Cl-X orbital of ClY in halogen-bonded complexes, with X being the atom of Y that is directly bonded to either H or Cl. For fixed HY, EOM-CCSD spin-spin coupling constants J(X-B1) are greater than J(X-Bn) for complexes B4H4:HY, even though the X-B1 distances are longer. B1 and Bn are the atoms at the apex and in the interacting face, respectively. Similarly, for complexes B4H4:ClY, J(Cl-B1) is greater than J(Cl-Bn). In the halogen-bonded complexes, both coupling constants correlate with the corresponding distances. PMID- 27399837 TI - Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility. AB - The extended synaptotagmins, E-Syt1, 2 and 3, are multiple C2 domain membrane proteins that are tethered to the endoplasmic reticulum and interact in a calcium dependent manner with plasma membrane phospholipids to form endoplasmic reticulum - plasma membrane junctions. These junctions have been implicated in the exchange of phospholipids between the 2 organelles. The E-Syts have further been implicated in receptor signaling and endocytosis and can interact directly with fibroblast growth factor and other cell surface receptors. Despite these multiple functions, the search for a requirement in vivo has been elusive. Most recently, we found that the genes for E-Syt2 and 3 could be inactivated without effect on mouse development, viability, fertility or morphology. We have now created insertion and deletion mutations in the last of the mouse E-Syt genes. We show that E-Syt1 is specifically expressed throughout the embryonic skeleton during the early stages of chrondrogenesis in a pattern quite distinct from that of E Syt2 or 3. Despite this, E-Syt1 is also not required for mouse development and propagation. We further show that even the combined inactivation of all 3 E-Syt genes has no effect on mouse viability or fertility in the laboratory. However, this inactivation induces an enhancement in the expression of the genes encoding Orp5/8, Orai1, STIM1 and TMEM110, endoplasmic reticulum - plasma membrane junction proteins that potentially could compensate for E-Syt loss. Given the multiple functions suggested for the E-Syts and their evolutionary conservation, our unexpected findings suggest that they may only provide a survival advantage under specific conditions that have as yet to be identified. PMID- 27399839 TI - Methadone as a Coanalgesic for Palliative Care Cancer Patients. AB - BACKGROUND: Methadone offers many advantages for treating cancer pain. However, its pharmacokinetic profile makes its use as a full-dose opioid challenging. OBJECTIVES: To evaluate the efficacy and safety of low-dose methadone as an adjunct to opioids in the treatment of cancer pain in palliative care patients. DESIGN: A cohort was followed retrospectively for up to 60 days after the initiation of methadone as a coanalgesic. SETTING/SUBJECTS: Patients were eligible if they were prescribed methadone as a coanalgesic for cancer pain management and followed by the palliative care team. MEASUREMENTS: The primary efficacy end point was reduction of pain intensity (11-point numerical rating scale). Variables associated with pain intensity reduction were explored using logistic regressions. Adverse events were collected throughout the follow-up. RESULTS: Seventy-two of the 146 subjects (49%) qualified as significant responders (>=30% reduction in pain intensity). Median time to significant response was seven days, and pain intensity on the day of methadone initiation predicted the response to treatment. The most frequently reported adverse events were drowsiness, confusion, constipation, and nausea. As expected in a palliative care population, there was a substantial amount of missing data. CONCLUSIONS: A significant reduction in pain can be seen rapidly after the addition of methadone as a coanalgesic, particularly among patients with high pain intensity. More studies are needed to corroborate the efficacy of methadone as an adjunct to opioids. PMID- 27399840 TI - Clinical and microbiologic features of dacryocystitis-related orbital cellulitis. AB - Dacryocystitis-related orbital cellulitis is a relatively rare condition, and large case series of this clinical entity have been reported. This study was undertaken to identify a larger cohort of patients with this ailment, with the intent of defining its clinical and microbiologic features. Case logs from four institutions were reviewed to identify patients that suffered from dacryocystitis related orbital cellulitis. A retrospective chart review was then performed to identify clinical features, management strategies, microbiologic features, and outcomes. A dedicated statistical software package was utilized to identify correlations between these variables. 13 patients (7 females, 6 males; mean age = 57.2 years, range = 7-89 years) were identified. One patient carried a diagnosis of immunosuppressive disease. All patients underwent emergent surgical drainage and received intravenous antibiotics. Primary acquired nasolacrimal duct obstruction was found to be the underlying etiology in nine cases (69.2%), whereas four patients suffered from specific causes of their obstructions. An average of 1.07 organisms/patient (standard deviation = 0.49 organisms/patient) were recovered from microbiologic cultures, and Gram-positive bacteria represented the majority of cultured organisms. All patients experienced either stable or improved vision upon discharge. The relationships between a specific etiology and the possibility of vision loss or the number of organisms cultured, between the number of organisms cultured and vision loss, and immunosuppression and vision loss or the number of organisms cultured were all not statistically significant (p > 0.05). Dacryocystitis-related orbital cellulitis most commonly occurs in adult patients who do not carry immunosuppressive diagnoses and suffer from primary obstructions. Multiple microbiologic species may cause this problem, although Gram-positive organisms are most common. With appropriate management, stable or improved vision can be achieved. PMID- 27399841 TI - Highly Efficient Process for Production of Biofuel from Ethanol Catalyzed by Ruthenium Pincer Complexes. AB - A highly efficient ruthenium pincer-catalyzed Guerbet-type process for the production of biofuel from ethanol has been developed. It produces the highest conversion of ethanol (73.4%, 0.02 mol% catalyst) for a Guerbet-type reaction, including significant amounts of C4 (35.8% yield), C6 (28.2% yield), and C8 (9.4% yield) alcohols. Catalyst loadings as low as 0.001 mol% can be used, leading to a record turnover number of 18 209. Mechanistic studies reveal the likely active ruthenium species and the main deactivation process. PMID- 27399842 TI - Postsynaptic, not presynaptic NMDA receptors are required for spike-timing dependent LTD induction. AB - Long-term depression (LTD) between cortical layer 4 spiny stellate cells and layer 2/3 pyramidal cells requires the activation of NMDA receptors (NMDARs). In young rodents, this form of LTD has been repeatedly reported to require presynaptic NMDARs for its induction. Here we show that at this synapse in the somatosensory cortex of 2- to 3-week-old rats and mice, postsynaptic, not presynaptic NMDARs are required for LTD induction. First, we find no evidence for functional NMDARs in L4 neuron axons using two-photon laser scanning microscopy and two-photon glutamate uncaging. Second, we find that genetic deletion of postsynaptic, but not presynaptic NMDARs prevents LTD induction. Finally, the pharmacology of the NMDAR requirement is consistent with a nonionic signaling mechanism. PMID- 27399843 TI - Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. AB - Axons in the mammalian CNS fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) is increased by visual stimulation or using chemogenetics, their axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell-growth promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate long distances and re-innervate the brain. Analysis of genetically labeled RGCs revealed that this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration, and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in adulthood. PMID- 27399845 TI - Vivid Manifestation of Nonergodicity in Glassy Propylene Carbonate at High Pressures. AB - As glasses are nonergodic systems, their properties should depend not only on external macroparameters, such as P and T, but also on the time of observation and thermobaric history. In this work, comparative ultrasonic studies of two groups of molecular propylene carbonate glasses obtained by quenching from a liquid at pressures of 0.1 and 1 GPa have been performed. Although the difference in the densities of the different groups of glasses is small (3-5%), they have significantly different elastic properties: the difference in the respective bulk moduli is 10-20%, and the difference in the respective shear moduli is 35-40% (!). This is due to the "closure of nanopores" in the glass obtained at 1 GPa. The pressure and temperature derivatives of the elastic moduli for these groups of glasses are also noticeably different. The glass-transition temperatures of glasses from different groups differ by 3-4 K. The character of absorption of ultrasound waves near the glass-transition temperature also differs for different groups of glasses. The differences in the behaviors of these groups of glasses disappear gradually above the glass-transition temperature, in the region of a liquid phase. Glasses with a wide diversity of physical properties can be obtained using various paths on the (T,P) diagram. PMID- 27399844 TI - Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior. AB - The ability to shift between repetitive and goal-directed actions is a hallmark of cognitive control. Previous studies have reported that adaptive shifts in behavior are accompanied by changes of neural activity in frontal cortex. However, neural and behavioral adaptations can occur at multiple time scales, and their relationship remains poorly defined. Here we developed an adaptive sensorimotor decision-making task for head-fixed mice, requiring them to shift flexibly between multiple auditory-motor mappings. Two-photon calcium imaging of secondary motor cortex (M2) revealed different ensemble activity states for each mapping. When adapting to a conditional mapping, transitions in ensemble activity were abrupt and occurred before the recovery of behavioral performance. By contrast, gradual and delayed transitions accompanied shifts toward repetitive responding. These results demonstrate distinct ensemble signatures associated with the start versus end of sensory-guided behavior and suggest that M2 leads in engaging goal-directed response strategies that require sensorimotor associations. PMID- 27399846 TI - Fabrication of Functional Nano-objects through RAFT Dispersion Polymerization and Influences of Morphology on Drug Delivery. AB - To study the influence of self-assembled morphologies on drug delivery, four different nano-objects, spheres, nanorods, nanowires, and vesicles having aldehdye-based polymer as core, were successfully prepared via alcoholic RAFT dispersion polymerization of p-(methacryloxyethoxy)benzaldehyde (MAEBA) using poly((N,N'-dimethylamino)ethyl methacrylate) (PDMAEMA) as a macro chain transfer agent (macro-CTA) for the first time. The morphologies and sizes of the four nano objects were characterized by TEM and DLS, and the spheres with average diameter (D) of 70 nm, the nanorods with D of 19 nm and length of 140 nm, and the vesicles with D of 137 nm were used in the subsequent cellular internalization, in vitro release, and intracellular release of the drug. The anticancer drug doxorubicin (DOX) was conjugated onto the core polymers of nano-objects through condensation reaction between aldehyde groups of the PMAEBA with primary amine groups in the DOX. Because the aromatic imine is stable under neutral conditions, but is decomposed in a weakly acidic solution, in vitro release of the DOX from the DOX loaded nano-objects was investigated in the different acidic solutions. All of the block copolymer nano-objects show very low cytotoxicity to HeLa cells up to the concentration of 1.2 mg/mL, but the DOX-loaded nano-objects reveal different cell viability and their IC50s increase as the following order: nanorods-DOX < vesicles-DOX < spheres-DOX. The IC50 of nanowires-DOX is the biggest among the four nano-objects owing to their too large size to be internalized. Endocytosis tests demonstrate that the internalization of vesicles-DOX by the HeLa cells is faster than that of the nanorods-DOX, and the spheres-DOX are the slowest to internalize among the studied nano-objects. Relatively more nanorods localized in the acidic organelles of the HeLa cells lead to faster intracellular release of the DOX, so the IC50 of nanorods is lower than that of the vesicles-DOX. PMID- 27399847 TI - Intergenerational Transmission of Internalizing Behavior: The Role of Maternal Psychopathology, Child Responsiveness and Maternal Attachment Style Insecurity. AB - BACKGROUND: Maternal depression and anxiety disorders are risk factors for the development of internalizing disorders in offspring. Maternal attachment has been discussed as one factor accounting for transmission. The aim of this study was to investigate child internalizing behavior at preschool age on a symptomatic and behavioral level and possible links to maternal mental health over time and maternal attachment style insecurity in a sample of postpartum depressed and anxious mothers. SAMPLING AND METHODS: Child internalizing behavior at preschool age was rated by the Child Behavior Checklist (CBCL), the Caregiver-Teacher Report Form (C-TRF), and during a mother-child free-play situation. We focused on child responsiveness as it has been linked to child internalizing behavior. Maternal attachment style insecurity was tested to mediate the link between maternal mental health (assessed postpartum and at preschool age with the Structured Clinical Interview for DSM-IV Axis-I Disorders, SCID-I) and child internalizing behavior/child responsiveness. Of the overall sample (n = 58), 28 women were diagnosed with postpartum depression and/or anxiety disorders according to DSM-IV, and 30 were healthy controls. Data were collected 3-9 months after delivery and at preschool age (mean = 4.6 years). RESULTS: At preschool age, children of postpartum depressed and anxious mothers were rated significantly higher on child internalizing behavior by mothers, fathers, and additional caregivers compared to the control group. Child internalizing behavior rated by mothers was influenced by current psychiatric symptoms; maternal attachment style insecurity did not mediate this link. During interaction, children in the clinical group displayed significantly less child responsiveness compared to the control group. Maternal attachment style insecurity mediated the relationship between maternal mental health over time and child responsiveness. CONCLUSIONS: The results emphasize the need for interventions focusing on mother child interaction and maternal attachment. PMID- 27399848 TI - The significance of incidental brain uptake on 68Ga-DOTATATE PET-CT in neuroendocrine tumour patients. AB - OBJECTIVE: Radiolabelled somatostatin analogues detect neuroendocrine tumours (NETs), but may reveal other tumour types. We examined the prevalence of possible meningioma in patients with known or suspected NETs imaged with Ga-DOTATATE PET computed tomography (CT) on the basis of central nervous system uptake and compared with findings on magnetic resonance and contrast-enhanced CT imaging. METHODS: Retrospective imaging reports from 313 patients who had undergone Ga DOTATATE PET imaging for primary or repeat NET staging were searched to identify suspected meningiomas on PET. Images were then compared with findings on subsequent complementary MRI or contrast-enhanced CT scanning (performed within mean+/-112 days of PET-CT) if available. RESULTS: Of 313 patients, 22 had regions of uptake suggestive of meningioma. MRI was available for 12 patients and contrast-enhanced CT was available for one patient. Of these, one patient with known von Hippel-Lindau syndrome had probable cerebellar NET metastasis. Six patient scans indicated lesions consistent with PET. Two of these reported initially did not comment on meningioma. No obvious lesion was found in the remaining six patients; however, five showed a possible correlation to venous structures. The mean maximum standardized uptake value+/-SEM for lesions in all 21 probable meningioma patients was 4.90+/-0.45. CONCLUSION: Ga-DOTATATE is a sensitive marker of probable meningioma and may identify small lesions not reported on subsequent MRI. Lesions clearly observed on PET were identified on review in half of patients where complementary MR or CT imaging was available. Haemangioblastoma and metastatic NETs may have focal peripheral uptake similar to meningioma on Ga-DOTATATE PET and should be considered in the differential. PMID- 27399849 TI - Nucleolin inhibitor GroA triggers reduction in epidermal growth factor receptor activation: Pharmacological implication for glial scarring after spinal cord injury. AB - Glial scarring, formed by reactive astrocytes, is one of the major impediments for regeneration after spinal cord injury (SCI). Reactive astrocytes become hypertrophic, proliferate and secrete chondroitin sulphate proteoglycans into the extracellular matrix (ECM). Many studies have demonstrated that epidermal growth factor receptors (EGFR) can mediate astrocyte reactivity after neurotrauma. Previously we showed that there is crosstalk between nucleolin and EGFR that leads to increased EGFR activation followed by increased cell proliferation. Treatment with the nucleolin inhibitor GroA (AS1411) prevented these effects in vitro and in vivo. In this study, we hypothesized that similar interactions may mediate astrogliosis after SCI. Our results demonstrate that nucleolin and EGFR interaction may play a pivotal role in mediating astrocyte proliferation and reactivity after SCI. Moreover, we demonstrate that treatment with GroA reduces EGFR activation, astrocyte proliferation and chondroitin sulphate proteoglycans secretion, therefore promoting axonal regeneration and sprouting into the lesion site. Our results identify, for the first time, a role for the interaction between nucleolin and EGFR in astrocytes after SCI, indicating that nucleolin inhibitor GroA may be used as a novel treatment after neurotrauma. A major barrier for axonal regeneration after spinal cord injury is glial scar created by reactive and proliferating astrocytes. EGFR mediate astrocyte reactivity. We showed that inhibition of nucleolin by GroA, reduces EGFR activation, which results in attenuation of astrocyte reactivity and proliferation in vivo and in vitro. EGFR, epidermal growth factor receptor. PMID- 27399851 TI - Triazole rizatriptan Induces Liver Toxicity through Lysosomal/Mitochondrial Dysfunction. AB - Background: Triptans are used as antimigraine agents. Some cases of hepatotoxicity by triptans have been reported. However, the exact mechanism of triptan-induced hepatotoxicity is not clear yet. Methods: In this study, the cytotoxic effects of rizatriptan were investigated in freshly isolated rat hepatocytes using accelerated cytotoxicity mechanism screening. We designed experiments to evaluate toxicity markers, such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, lysosomal membrane integrity and the amount of reduced and oxidized glutathione in the rizatriptan-treated hepatocytes. Results: Cytotoxicity caused by rizatriptan in rat hepatocytes was concentration-dependent. An increase in ROS formation accompanied by a significant rise in lipid peroxidation, mitochondrial depolarization and loss of lysosomal membrane integrity was observed. Cellular glutathione reservoirs were decreased and a significant amount of oxidized glutathione was formed. All the aforementioned rizatriptan-induced cellular events were significantly (p<0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Also, the present results demonstrated that CYP450 is involved in rizatriptan-induced oxidative stress and cytotoxicity mechanism and different CYP450 inducers had different effects on the toxicity. Conclusion: It is suggested that the adverse effect of rizatriptan towards hepatocytes is mediated by oxidative stress and the hepatocytes lysosomes and mitochondria play an important role in rizatriptan induced cell injury. PMID- 27399852 TI - A quantum chemistry study of curvature effects on boron nitride nanotubes/nanosheets for gas adsorption. AB - Quantum chemistry calculations were performed to investigate the effect of the surface curvature of a Boron Nitride (BN) nanotube/nanosheet on gas adsorption. Curved boron nitride layers with different curvatures interacting with a number of different gases including noble gases, oxygen, and water on both their convex and concave sides of the surface were studied using density functional theory (DFT) with a high level dispersion corrected functional. Potential energy surfaces of the gas molecules interacting with the selected BN surfaces were investigated. In addition, the charge distribution and electrostatic potential contour of the selected BN surfaces are discussed. The results reveal how the curvature of the BN surfaces affects gas adsorption. In particular, small curvatures lead to a slight difference in the physisorption energy, while large curvatures present distinct potential energy surfaces, especially for the short range repulsion. PMID- 27399850 TI - A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation. AB - Bioengineered tissue scaffolds in combination with cells hold great promise for tissue regeneration. The aim of this study was to determine how the chemistry and fiber orientation of engineered scaffolds affect the differentiation of mesenchymal stem cells (MSCs). Adipogenic, chondrogenic, and osteogenic differentiation on aligned and randomly orientated electrospun scaffolds of Poly (lactic-co-glycolic) acid (PLGA) and Polydioxanone (PDO) were compared. MSCs were seeded onto scaffolds and cultured for 14 days under adipogenic-, chondrogenic-, or osteogenic-inducing conditions. Cell viability was assessed by alamarBlue metabolic activity assays and gene expression was determined by qRT-PCR. Cell scaffold interactions were visualized using fluorescence and scanning electron microscopy. Cells grew in response to scaffold fiber orientation and cell viability, cell coverage, and gene expression analysis showed that PDO supports greater multilineage differentiation of MSCs. An aligned PDO scaffold supports highest adipogenic and osteogenic differentiation whereas fiber orientation did not have a consistent effect on chondrogenesis. Electrospun scaffolds, selected on the basis of fiber chemistry and alignment parameters could provide great therapeutic potential for restoration of fat, cartilage, and bone tissue. This study supports the continued investigation of an electrospun PDO scaffold for tissue repair and regeneration and highlights the potential of optimizing fiber orientation for improved utility. (c) 2016 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2843-2853, 2016. PMID- 27399853 TI - Correction: Charge-tunnelling and self-trapping: common origins for blinking, grey-state emission and photoluminescence enhancement in semiconductor quantum dots. AB - Correction for 'Charge-tunnelling and self-trapping: common origins for blinking, grey-state emission and photoluminescence enhancement in semiconductor quantum dots' by M. A. Osborne, et al., Nanoscale, 2016, 8, 9272-9283. PMID- 27399854 TI - Prospects of osteoactivin in tissue regeneration. AB - INTRODUCTION: Osteoactivin (OA) was first discovered in an osteopetrotic rat model using mRNA differential display a decade ago and has been studied recently. OA in bone tissue can directly or indirectly regulate the differentiation of osteoblasts by influencing cell behaviours, such as proliferation and adhesion, as well as inducing serial signal cascades, which would be of great importance in the field of tissue engineering. The results of recent studies have further demonstrated that OA plays a critical role in the differentiation and function of cells, especially in bone formation and fracture healing. Areas covered: The discovery, structure, and function of OA as well as its therapeutic potential in tissue regeneration of bone defects, kidney injury, liver damage, and muscle atrophy. Expert opinion: OA has great potential in promoting the regeneration of damaged tissues, particularly bone tissue, which is supported by a large body of data. Future studies should focus on exploring the underlying mechanism of OA as well as pursuing the ideal form of OA-related regenerative medicine. PMID- 27399855 TI - LGBT care: There has been progress. PMID- 27399856 TI - To the Editor: Blood pressure targets. PMID- 27399857 TI - To the Editor: Blood pressure targets. PMID- 27399858 TI - In Reply: Blood pressure targets. PMID- 27399859 TI - A serpiginous, itchy rash on the foot. PMID- 27399860 TI - Are we causing anemia by ordering unnecessary blood tests? PMID- 27399861 TI - A female liver transplant recipient asks: Can I become pregnant? PMID- 27399862 TI - Ovarian hyperstimulation syndrome as a complication of molar pregnancy. PMID- 27399863 TI - Alpha-1 antitrypsin deficiency: An underrecognized, treatable cause of COPD. AB - Alpha-1 antitrypsin deficiency is common but underrecognized. Because delayed diagnosis is thought to be associated with adverse outcomes, clinicians are encouraged to follow available guidelines and test for the disease in all symptomatic adults with fixed airflow obstruction. The weight of available evidence supports the biochemical and clinical efficacy of intravenous augmentation therapy. Promising new therapies are being investigated. PMID- 27399864 TI - Detecting cancer: Pearls for the primary care physician. AB - Five-year survival rates have improved over the past 40 years for nearly all types of cancer, partially thanks to early detection and prevention. Since patients typically present to their primary care physician with initial symptoms, it is vital for primary care physicians to accurately diagnose common cancers and to recognize unusual presentations of highly curable cancers such as Hodgkin lymphoma and testicular cancers, for which the 5-year overall survival rates are greater than 85%. This paper reviews these cancers and provides clinically relevant pearls from an oncologic perspective for physicians who are the first point of contact. PMID- 27399865 TI - Premature ventricular contractions: Reassure or refer? AB - When patients present with palpitations, the primary care physician can perform the initial evaluation and treatment for premature ventricular contractions (PVCs). Many patients need only reassurance and do not need to see a cardiologist. PMID- 27399866 TI - Best practices in LGBT care: A guide for primary care physicians. AB - Lesbian, gay, bisexual, and transgender (LGBT) people have unique healthcare needs. While all LGBT people are at an increased risk for mental health and substance abuse disorders, certain health conditions vary by group. Overweight and obesity are more common in lesbian and bisexual women, whereas sexual minority men are at increased risk for infections such as human immunodeficiency virus (HIV) and syphilis. Breast, cervical, and prostate cancer screening should be offered to all LGBT individuals according to national guidelines and with consideration of a transgender person's natal and surgical anatomy. PMID- 27399867 TI - The evolution of office notes and the electronic medical record: The CAPS note. AB - The advent of the electronic medical record (EMR) combined with an expansion of information required by medicolegal and billing departments has transformed the progress note from a succinct note into an often unwieldy data-dump unable to concisely convey the physician's medical reasoning. We describe a new note format -CAPS, which stands for concern, assessment, plan, and supporting data--to streamline the communication of the patient's problem, the practitioner's assessment and plan, and the medical reasoning to support the plan. PMID- 27399868 TI - Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer. AB - Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 +/- 0.42 vs 3.78 +/- 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 +/- 1.50 vs 8.42 +/- 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA SCH1 was observed in the liver (4.21 +/- 0.42%ID/g) and kidney (3.41 +/- 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients. PMID- 27399869 TI - Testing Cross-Cultural Generalizability of the Task and Ego Orientation in Sport Questionnaire across American and Chinese Samples. AB - This paper examines the factor structure and measurement invariance of the Task and Ego Orientation in Sport Questionnaire (TEOSQ) across American and Chinese samples. Results based on the mean and covariance structure analyses supported configural invariance, metric invariance and scalar invariance across groups. Latent means analyses revealed that American sample had significantly higher mean scores on task and ego orientations than the Chinese sample. The findings suggest that the TEOSQ is a valid and reliable instrument in assessing achievement motivation across these two diverse populations. PMID- 27399871 TI - Effects of varying the ratio of cooked to uncooked potato on the microbial fuel cell treatment of common potato waste. AB - The effect of varying the ratio of cooked to uncooked potato in the performance of microbial fuel cell (MFC) treating common potato waste was investigated. Four MFCs were fed with a ratio of cooked (boiled) to uncooked (i.e. waste) potato of 0, 48.7, 67.3 and 85.6%. Respectively, the columbic efficiency was estimated as 53.5, 70.5, 92.7 and 71.1%, indicating significantly enhanced electricity generation and waste degradation at an initial feedstock mixing ratio of 2/3 cooked to 1/3 uncooked potato. The hydrolysis rate parameter (estimated using a first-order sequential hydrolysis and degradation model) increased from 0.061 to 0.191day(-1) as cooked potato was added which increased electricity generation efficiency from 24.6 to 278.9mA/m(2)/d and shortened the startup time for maximum current density from 25 to 5days. The potato slurries' chemical oxygen demand (COD) decreased by 86.6, 83.9, 84.1 and 86.3%, respectively, indicating no relationship exists between the fraction of boiled potato and the amount of COD reduction. PMID- 27399870 TI - Terminal Duplex Stability and Nucleotide Identity Differentially Control siRNA Loading and Activity in RNA Interference. AB - Efficient short interfering RNA (siRNA)-mediated gene silencing requires selection of a sequence that is complementary to the intended target and possesses sequence and structural features that encourage favorable functional interactions with the RNA interference (RNAi) pathway proteins. In this study, we investigated how terminal sequence and structural characteristics of siRNAs contribute to siRNA strand loading and silencing activity and how these characteristics ultimately result in a functionally asymmetric duplex in cultured HeLa cells. Our results reiterate that the most important characteristic in determining siRNA activity is the 5' terminal nucleotide identity. Our findings further suggest that siRNA loading is controlled principally by the hybridization stability of the 5' terminus (Nucleotides: 1-2) of each siRNA strand, independent of the opposing terminus. Postloading, RNA-induced silencing complex (RISC) specific activity was found to be improved by lower hybridization stability in the 5' terminus (Nucleotides: 3-4) of the loaded siRNA strand and greater hybridization stability toward the 3' terminus (Nucleotides: 17-18). Concomitantly, specific recognition of the 5' terminal nucleotide sequence by human Argonaute 2 (Ago2) improves RISC half-life. These findings indicate that careful selection of siRNA sequences can maximize both the loading and the specific activity of the intended guide strand. PMID- 27399872 TI - Inter-laboratory optimization of protein extraction, separation, and fluorescent detection of endogenous rice allergens. AB - In rice, several allergens have been identified such as the non-specific lipid transfer protein-1, the alpha-amylase/trypsin-inhibitors, the alpha-globulin, the 33 kDa glyoxalase I (Gly I), the 52-63 kDa globulin, and the granule-bound starch synthetase. The goal of the present study was to define optimal rice extraction and detection methods that would allow a sensitive and reproducible measure of several classes of known rice allergens. In a three-laboratory ring-trial experiment, several protein extraction methods were first compared and analyzed by 1D multiplexed SDS-PAGE. In a second phase, an inter-laboratory validation of 2D-DIGE analysis was conducted in five independent laboratories, focusing on three rice allergens (52 kDa globulin, 33 kDa glyoxalase I, and 14-16 kDa alpha amylase/trypsin inhibitor family members). The results of the present study indicate that a combination of 1D multiplexed SDS-PAGE and 2D-DIGE methods would be recommended to quantify the various rice allergens. PMID- 27399873 TI - Letter to the Editor: Human Pluripotent Stem Cells Release Oncogenic Soluble E Cadherin. AB - Since their discovery, human pluripotent stem cells (hPSCs) including embryonic and induced pluripotent stem cells hold great promise in disease modeling and regenerative medicine. Despite intensive research and remarkable progress, it is becoming increasingly acknowledged that their yet incomplete, biological characterisation represents one of the major drawbacks to their successful translation into the clinics. The expression of the transmembrane protein E cadherin in hPSCs is well defined to be pivotal to the maintenance of the pluripotent state by mediating intercellular adhesion and intracellular signaling. Next to these canonical functions, were here report for the first time that hPSCs are subject to matrix metalloproteinase-dependent E-cadherin ectodomain shedding. This generates a ~80-kD, soluble E-cadherin fragment which is released into the extracellular space, and which is well described to exert paracrine signaling activity and classified as being oncogenic. Collectively, this finding does not only improve our knowledge on the signaling crosstalk between hPSCs and their cellular environment and the type and nature of the paracrine signals produced by these cells, but also has clear implications for the development of efficient and safe stem cell-based therapies. Stem Cells 2016;34:2443-2446. PMID- 27399874 TI - Effect of Electron-Beam Irradiation on Organic Semiconductor and Its Application for Transistor-Based Dosimeters. AB - The effects of electron-beam irradiation on the organic semiconductor rubrene and its application as a dosimeter was investigated. Through the measurements of photoluminescence and the ultraviolet photoelectron spectroscopy, we found that electron-beam irradiation induces n-doping of rubrene. Additionally, we fabricated rubrene thin-film transistors with pristine and irradiated rubrene, and discovered that the decrease in transistor properties originated from the irradiation of rubrene and that the threshold voltages are shifted to the opposite directions as the irradiated layers. Finally, a highly sensitive and air stable electron dosimeter was fabricated based on a rubrene transistor. PMID- 27399875 TI - Borderline personality disorder associates with violent criminality in women: A population based follow-up study of adolescent psychiatric inpatients in Northern Finland. AB - Various psychiatric problems in adolescence and early adulthood have been shown to associate with criminal behaviour. In this study the association of personality disorders (PDs) with criminal behaviour was examined in adolescents treated in psychiatric hospitals. The study sample consisted of 508 adolescents (age 13-17) admitted to acute psychiatric impatient care between April 2001 and March 2006. Crime data was obtained from the Finnish Legal Register Centre on September 2013. The Schedule for Affective Disorder and Schizophrenia for School Age Children Present and Lifetime (K-SADS-PL) was used to assess psychiatric diagnoses in adolescence. The information on PDs in early adulthood was based on follow-up information on psychiatric treatments in either out- or inpatient settings until the end of 2012, and was extracted from the National Care Register for Health Care provided by the Finnish National Institute for Health and Welfare. A total of 22 (39%) of the 57 subjects with PD had committed a crime. In women, the likelihood for violent criminality was significantly increased in those with Borderline PD (OR 6.09, CI 1.24-29.84, p=0.009) and was also associated with conduct disorder (OR 4.26, CI 1.38-13.19, p=0.012), child welfare placement (OR 11.82, CI 3.61-38.76, p<0.001) and parent's substance use disorder (OR 7.74, CI 2.30-26.10, p=0.001). In men, no association was observed between PD and any kind of criminal behaviour. Significant predictors for violent criminality in males were conduct disorder (OR 4.05, CI 1.75-9.38, p=0.001), substance use disorder (OR 2.51, CI 1.22-5.17, p=0.012) and special services at school (OR 2.58, CI 1.16-5.76, p=0.021). Females with Borderline PD showed an increased risk for violent offending. This suggests Borderline PD as a potential explanatory factor for violent assaults by females and highlights the importance of recognizing the risk for violence in young women with a Borderline PD. PMID- 27399876 TI - Differential Responses to Vitamin D2 and Vitamin D3 Are Associated With Variations in Free 25-Hydroxyvitamin D. AB - 25-Hydroxyvitamin D (25D) circulates bound primarily to serum vitamin D binding protein (DBP), with DBP showing higher binding affinity for 25D3 than 25D2. We therefore hypothesized that vitamin D2 (D2) promotes higher serum levels of unbound 25D (free 25D), with different functional responses, relative to vitamin D3 (D3). Week 3 C56BL/6 mice were placed on diets containing either D2 or D3 alone (both 1000 IU/kg). At week 8 and week 16, D2 mice had only 25D2 in circulation (26.6 +/- 1.9 and 33.3 +/- 4.4 ng/mL), and D3 mice had only 25D3 (28.3 +/- 2.0 and 31.7 +/- 2.1 ng/mL). At week 8 (44.5 +/- 6.4 vs 62.4 +/- 11.6 pg/mL, P < .05) and week 16 (78.4 +/- 12.6 vs 95.5 +/- 11.6), D2 mice had lower serum 1,25-dihydroxyvitamin D relative to D3 mice. By contrast, measured free 25D was significantly higher in D2 mice at week 8 (16.8 +/- 0.65 vs 8.4 +/- 0.63 pg/mL, P < .001) and week 16 (17.4 +/- 0.43 vs 8.4 +/- 0.44, P < .001). A two-way ANOVA of bone histomorphometry showed that week 8 D2 mice had significantly higher osteoclast surface/bone surface, eroded surface/bone surface, and mineral apposition rate compared with D3 mice. Osteoblast surface/bone surface was higher in week 8 D2 females but not week 8 D2 males. At week 16, D2 mice had significantly higher bone volume/total volume and trabecular number compared with D3 mice. Differences in bone phenotype were observed despite D2 mice reaching similar serum 25D levels and lower 1,25D levels compared with D3 mice. These data indicate that 25D2 binds less well to DBP than 25D3, with resulting higher levels of free 25D promoting differential effects on bone in mice exposed to D2 alone. PMID- 27399877 TI - Characterization of Neuropeptide B (NPB), Neuropeptide W (NPW), and Their Receptors in Chickens: Evidence for NPW Being a Novel Inhibitor of Pituitary GH and Prolactin Secretion. AB - The 2 structurally and functionally related peptides, neuropeptide B (NPB) and neuropeptide W (NPW), together with their receptor(s) (NPBWR1/NPBWR2) constitute the NPB/NPW system, which acts mainly on the central nervous system to regulate many physiological processes in mammals. However, little is known about this NPB/NPW system in nonmammalian vertebrates. In this study, the functionality and expression of this NPB/NPW system and its actions on the pituitary were investigated in chickens. The results showed that: 1) chicken NPB/NPW system comprises an NPB peptide of 28 amino acids (cNPB28), an NPW peptide of 23 or 30 amino acids (cNPW23/cNPW30), and their 2 receptors (cNPBWR1 and cNPBWR2), which are highly homologous to their human counterparts. 2) Using a pGL3-CRE-luciferase reporter system, we demonstrated that cNPBWR2 expressed in Chinese hamster ovary cells can be potently activated by cNPW23 (not cNPB28), and its activation inhibits the intracellular cAMP signaling pathway, whereas cNPBWR1 shows no response to peptide treatment, suggesting a crucial role of cNPBWR2 in mediating cNPW/cNPB actions. 3) Quantitative real-time PCR revealed that cNPW and cNPB are widely expressed in chicken tissues, including hypothalamus, whereas cNPBWR1 and cNPBWR2 are mainly expressed in brain or pituitary. 4) In accordance with abundant cNPBWR2 expression in pituitary, cNPW23 could dose dependently inhibit GH and prolactin secretion induced by GHRH and vasoactive intestinal polypeptide, respectively, in cultured chick pituitary cells, as monitored by Western blotting. Collectively, our data reveal a functional NPB/NPW system in birds and offer the first proof that NPW can act directly on pituitary to inhibit GH/prolactin secretion in vertebrates. PMID- 27399878 TI - The NADPH Oxidase Nox2 Mediates Vitamin D-Induced Vascular Regeneration in Male Mice. AB - 1alpha,25-dihydroxy-vitamin D3 (1,25D) exerts protective effects in the vascular system and promotes myeloid cell differentiation, which are important sources of reactive oxygen species. Given that myeloid cell reactive oxygen species derives from Nox-family NADPH oxidases, we hypothesized that this enzyme family contributes to the beneficial effects of 1,25D on vascular regeneration. The function of Nox enzymes in this context was studied in the murine carotid artery electric injury regeneration model. Male mice were treated with daily injections of 1,25D (100 ng/kg . d) for 5 days and carotid injury was induced after 3 days. After injury, 1,25D increased the expression of Nox2 in the carotid artery. As determined by Evans blue staining on day 6, 1,25D improved vascular regeneration in a Nox2-dependent manner. Healing was lost in mice knockout for Nox2, but not in Nox1 or Nox4, knockout mice. Tissue specific knockouts demonstrated that the myeloid, but not the endothelial Nox2, was required for this effect. Mechanistically, the combination of injury and 1,25D induced the mobilization of angiogenic myeloid cells (AMCs) and increased the vascular expression of the cytokine stem cell derived factor (SDF)1, which attracts AMCs to the site of injury. Vitamin D in a Nox2-dependent manner activated MAPKs, and these are known to contribute to SDF1 induction. Accordingly, SDF1 induction was lost after deletion of Nox2. By inducing SDF1 and enhancing the number of AMCs, VitD3 is a novel approach to promote vascular repair. PMID- 27399879 TI - PET imaging in extratemporal epilepsy requires consideration of electroclinical findings. AB - OBJECTIVE: The study aimed to assess the relevance of interictal temporal glucose hypometabolism in patients with extratemporal epilepsy (ETE) by analyzing its association with a seizure semiology suggestive for temporal seizure involvement and the presence of temporal interictal epileptiform discharges (IEDs). METHODS: We retrospectively reviewed the database of our epilepsy monitoring unit for patients with ETE, in whom long-term EEG-video-monitoring and [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) had been performed. The localization of IEDs and the glucose hypometabolism were compared. RESULTS: Almost half (46%) of the 63 ETE patients had IEDs localized in the temporal lobe. Most patients (87.5%; 7/8) with temporal IEDs and an ipsitemporal hypometabolism showed seizure semiology suggestive of temporal or limbic system involvement in contrast to only 31.0% (9/29, p=0.01) in patients without temporal IEDs nor temporal hypometabolism. Those patients also showed an ictal seizure pattern spread into the ipsitemporal lobe, compared with 75.9% (22/29, n.s.) in patients without temporal IEDs nor temporal hypometabolism. Both, extratemporal (ipsilateral in 82.1%; 23/28 patients) and temporal (ipsilateral in 78.6%; 11/14 patients) hypometabolism significantly (p<0.05) lateralized to the epileptogenic hemisphere. CONCLUSION: The common temporal glucose hypometabolism in ETE patients reflects a remote epileptic dysfunction arising from extratemporal epileptogenic zones. Thus, interpretation of interictal FDG-PET results requires consideration of EEG results and seizure semiology to avoid false localization particularly in non-lesional epilepsy. PMID- 27399880 TI - A Cinderella Tale: Can New Shoes Change the Life of a Person With Knee Osteoarthritis? PMID- 27399881 TI - Application of the Dimensional Reduction Formalism to Pb12[Li2(P2O7)2(P4O13)2](P4O13): a Phosphate Containing Three Types of Isolated P O Groups. AB - A new phosphate, Pb12[Li2(P2O7)2(P4O13)2](P4O13), containing three types of isolated polyphosphate anionic groups [P2O7], and two types of [P4O13] has been successfully synthesized by using Li2O as dimensional reduction agent to dismantle Pb3P4O13. The isolation of [P2O7] and two types of [P4O13] with different symmetries in the title compound mainly benefits from the large number and flexible coordination of the Pb(2+) cations. PMID- 27399882 TI - Strategies for recruiting South Asian women to cancer screening research and the lessons learnt. AB - AIMS: The aim of this study was to describe and discuss the recruitment strategies used in a research study of cervical cancer screening among South Asian women, the challenges encountered and the lessons learnt from the experience. BACKGROUND: Ethnic minority populations face different barriers to participating in research studies. Strategies have been developed to recruit this population to health-related research in Western countries, but there is little information about such research in the Asian region. DESIGN: Discussion paper. DATA SOURCES: The discussion is based on our previous experience. The source of this experience is the recruitment strategies used, their results and the challenges encountered during the process. IMPLICATIONS FOR NURSING: Culturally, relevant strategies and maintaining good relationships with stakeholders improved participant recruitment. Familiarity with South Asians' traditional calendar - when cultural and religious festivals are held every year - would aid the setting up of appropriate schedules for participant recruitment, either before or after the periods when they cannot be reached, such as Ramadan. South Asian women are often busy with childcare and housework. This is their major responsibility in the family and any failure to fulfil such duties is a source of stress and may foster feelings of guilt. A better understanding of their daily routines is therefore important. Such information enables the establishment of daily meeting schedules to increase the success rate of recruitment. CONCLUSION: Recruitment is a tedious process, but appropriate planning and taking account of cultural and religious practices and daily schedules will help to improve its rate of success. PMID- 27399883 TI - Psychological Features and Sexual Beliefs Characterizing Self-Labeled Asexual Individuals. AB - The present study was aimed at exploring and describing potential psychological and cognitive features characterizing asexual individuals. A web survey targeting a community of single and highly educated asexual individuals (68 women and 19 men) and matching controls (58 women and 19 men) was carried out in volunteers over 18 years old. Participants responded to a set of questions assessing personality traits, state psychopathological dimensions, and sexual beliefs. Findings on asexual women revealed that they reported higher levels of neuroticism, depression, phobic anxiety, personal sensitivity, as well as lower extraversion and conscientiousness than nonasexual women; also, asexual women reported more sexually conservative beliefs (including regarding sexual desire as a sin), beliefs related to the negative impact of age in sexuality, and the primacy of affection in sexual intercourse. Findings on asexual men showed that they reported more neuroticism, openness, psychoticism, and less extraversion. Findings on sexual beliefs showed that asexual men reported more sexually conservative beliefs, more beliefs related to the propensity for believing that women may use sex as a means to subjugate men, and beliefs related to the idea that erectile performance is central to female satisfaction. Findings further suggested that some of these features may have tapped into asexual individuals' religious status. PMID- 27399884 TI - Physical activity patterns in healthy middle-aged women. AB - : Exercise in healthy female adults around the menopausal transition has been routinely examined in leisure activities alone, potentially discounting the physical activity (PA) that is accumulated in household and outdoor domains. The purpose of this study was to quantify PA in healthy middle-aged women and to examine the extent to which the Center for Disease Control (CDC) PA guidelines were met through leisure, household, and outdoor activities. METHODS: 440 healthy women, 51-64 years old, BMI >=18.5 or < 40 kg/m2, participated in the study using the Lifetime Physical Activity Questionnaire (LPAQ) to quantify PA. RESULTS: 25.91% met the CDC PA guidelines if leisure time alone was examined. When multiple domains were included, 73.41% of the women met the PA guidelines. This percentage is much higher than the reported 20.6% of U.S. adults who met the guidelines in 2011. PA in women may be underrepresented in data limited to leisure time PA. PMID- 27399885 TI - Synthesis and SAR studies of potent H(+)/K(+)-ATPase inhibitors of quinazolinone Schiff's base analogues. AB - A series of quinazolinone derived Schiff base derivatives 7-36 were synthesized and characterized by analytical and spectroscopic techniques. The synthesized analogues were screened for their in vitro H(+)/K(+)-ATPase inhibition. Most of the compounds showed excellent activity, compared to that of omeprazole, a reference drug. In particular, hydroxy and methoxy derivatives 13-24 were the most active compounds possessing a significant increase for different substituents on the benzene ring thus, contributing positively to gastric H(+)/K(+)-ATPase inhibition. Preliminary structure-activity relationship revealed that the compounds 13-24 with electron donating moiety (OH, OCH3) were found to be excellent activity and compounds 9-12 and 25-36 with electron withdrawing moiety (Cl, F, NO2 and Br) were found to be least antiulcer agents. PMID- 27399886 TI - Bone repair and stem cells. AB - Bones are an important component of vertebrates; they grow explosively in early life and maintain their strength throughout life. Bones also possess amazing capabilities to repair-the bone is like new without a scar after complete repair. In recent years, a substantial progress has been made in our understanding on mammalian bone stem cells. Mouse genetic models are powerful tools to understand the cell lineage, giving us better insights into stem cells that regulate bone growth, maintenance and repair. Recent findings about these stem cells raise new questions that require further investigations. PMID- 27399887 TI - Skeletal muscle dedifferentiation during salamander limb regeneration. AB - Salamanders can regenerate entire limbs throughout their life. A critical step during limb regeneration is formation of a blastema, which gives rise to the new extremity. Salamander limb regeneration has historically been tightly linked to the term dedifferentiation, however, with refined research tools it is important to revisit the definition of dedifferentiation in the context. To what extent do differentiated cells revert their differentiated phenotypes? To what extent do progeny from differentiated cells cross lineage boundaries during regeneration? How do cell cycle plasticity and lineage plasticity relate to each other? What is the relationship between dedifferentiation of specialized cells and activation of tissue resident stem cells in terms of their contribution to the new limb? Here we highlight these problems through the case of skeletal muscle. PMID- 27399888 TI - Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. AB - A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. PMID- 27399890 TI - Correction: A Human Trypanosome Suppresses CD8+ T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4+ Foxp3+ T Cells. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005698.]. PMID- 27399889 TI - Keep wetlands wet: the myth of sustainable development of tropical peatlands - implications for policies and management. AB - Pristine tropical peat swamp forests (PSFs) represent a unique wetland ecosystem of distinctive hydrology which support unique biodiversity and globally significant stores of soil carbon. Yet in Indonesia and Malaysia, home to 56% of the world's tropical peatland, they are subject to considerable developmental pressures, including widespread drainage to support agricultural needs. In this article, we review the ecology behind the functioning and ecosystem services provided by PSFs, with a particular focus on hydrological processes as well as the role of the forest itself in maintaining those services. Drawing on this, we review the suitability of current policy frameworks and consider the efficacy of their implementation. We suggest that policies in Malaysia and Indonesia are often based around the narrative of oil palm and other major monocrops as drivers of prosperity and development. However, we also argue that this narrative is also being supported by a priori claims concerning the possibility of sustainability of peat swamp exploitation via drainage-based agriculture through the adherence to best management practices. We discuss how this limits their efficacy, uptake and the political will towards enforcement. Further, we consider how both narratives (prosperity and sustainability) clearly exclude important considerations concerning the ecosystem value of tropical PSFs which are dependent on their unimpacted hydrology. Current research clearly shows that the actual debate should be focused not on how to develop drainage-based plantations sustainably, but on whether the sustainable conversion to drainage-based systems is possible at all. PMID- 27399891 TI - Letters. PMID- 27399893 TI - Brief reports. PMID- 27399896 TI - Scanning sports. PMID- 27399894 TI - Flexibility for Tennis and Racquetball. PMID- 27399897 TI - Aging Man Feels Ageless in Autumn. PMID- 27399899 TI - Bruno Balke Welcomes-and Creates-Avalanches. PMID- 27399898 TI - Sexual Differences in Heat Stress Response. AB - In their response to heat stress, men and women exhibit differences in heart rate and sweat rate, among other things. The reason is apparently not hormonal but due to different utilization of thermoregulatory mechanisms available to each. Menstruation does not appear to make women more vulnerable to heat stress. PMID- 27399900 TI - Deafness in Running. PMID- 27399901 TI - Where are they now? PMID- 27399902 TI - News From ACSM. PMID- 27399903 TI - Characterization of a highly virulent and antimicrobial-resistant Acinetobacter baumannii strain isolated from diseased chicks in China. AB - Poultry husbandry is a very important aspect of the agricultural economy in China. However, chicks are often susceptible to infectious disease microorganisms, such as bacteria, viruses and parasites, causing large economic losses in recent years. In the present study, we isolated an Acinetobacter baumannii strain, CCGGD201101, from diseased chicks in the Jilin Province of China. Regression analyses of virulence and LD50 tests conducted using healthy chicks confirmed that A. baumannii CCGGD201101, with an LD50 of 1.81 (+/-0.11) * 10(4) CFU, was more virulent than A. baumannii ATCC17978, with an LD50 of 1.73 (+/-0.13) * 10(7) CFU. Moreover, TEM examination showed that the pili of A. baumannii CCGGD201101 were different from those of ATCC17978. Antibiotic sensitivity analyses showed that A. baumannii CCGGD201101 was sensitive to rifampicin but resistant to most other antibiotics. These results imply that A. baumannii strain CCGGD201101 had both virulence enhancement and antibiotic resistance characteristics, which are beneficial for A. baumannii survival under adverse conditions and enhance fitness and invasiveness in the host. A. baumannii CCGGD20101, with its high virulence and antimicrobial resistance, may be one of the pathogens causing death of diseased chicks. PMID- 27399904 TI - An Experience Oriented-Convergence Improved Gravitational Search Algorithm for Minimum Variance Distortionless Response Beamforming Optimum. AB - An experience oriented-convergence improved gravitational search algorithm (ECGSA) based on two new modifications, searching through the best experiments and using of a dynamic gravitational damping coefficient (alpha), is introduced in this paper. ECGSA saves its best fitness function evaluations and uses those as the agents' positions in searching process. In this way, the optimal found trajectories are retained and the search starts from these trajectories, which allow the algorithm to avoid the local optimums. Also, the agents can move faster in search space to obtain better exploration during the first stage of the searching process and they can converge rapidly to the optimal solution at the final stage of the search process by means of the proposed dynamic gravitational damping coefficient. The performance of ECGSA has been evaluated by applying it to eight standard benchmark functions along with six complicated composite test functions. It is also applied to adaptive beamforming problem as a practical issue to improve the weight vectors computed by minimum variance distortionless response (MVDR) beamforming technique. The results of implementation of the proposed algorithm are compared with some well-known heuristic methods and verified the proposed method in both reaching to optimal solutions and robustness. PMID- 27399905 TI - Recent Progress for the Utilization of Curcuma longa, Piper nigrum and Phoenix dactylifera Seeds against Type 2 Diabetes. AB - Background: Diabetes mellitus is an important human disease afflicting many from various walks of life in different countries. Even though modern medicines contribute a variety of effective treatment options, they can have several unfavourable effects. The intention of this review is to organize and discuss various studies that have been previously conducted on the effectiveness of these herbal plants in diabetes. Method: By using various electronic search databases, a comprehensive English literature search was conducted. Different search terms were used by combining all the search fields in titles, abstracts and keywords. Results: Curcuma longa,a spice, is commonly known as turmeric and belongs to the family Zingiberaceae. Piper nigrumis also a spice, commonly called black pepper, and belongs to the family Piperaceae. Phoenix dactylifera, commonly known as date fruit, belongs to the family Arecaceae. From ancient times, they have been traditionally used for the treatment of various diseases. Among various activities, regulation of hyperglycaemia is considered one of their important effects. One of the aetiological factors implicated in the development of diabetes and its complications is the damage induced by free radicals. Antioxidant properties of antidiabetic compounds would be more beneficial. Extracts of these plants have shown hypoglycaemic and hypolipidaemic effects by the involvement of several mechanisms. In the future, further studies are needed to investigate the mechanisms involved in their hypoglycaemic potential and their active constituents as synthetic analogues. Conclusions: This review focusses on some medicinal plants that have antidiabetic effect, thus contributing to the reduction of risk factors associated with diabetes, and related beneficial effects are compiled. PMID- 27399906 TI - Solvent-Free Photooxidation of Alkanes by Dioxygen with 2,3-Dichloro-5,6-dicyano p-benzoquinone via Photoinduced Electron Transfer. AB - Photooxidation of alkanes by dioxygen occurred under visible light irradiation of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) which acts as a super photooxidant. Solvent-free hydroxylation of cyclohexane and alkanes is initiated by electron transfer from alkanes to the singlet and triplet excited states of DDQ to afford the corresponding radical cations and DDQ(?-) , as revealed by femtosecond laser induced transient absorption measurements. Alkane radical cations readily deprotonate to produce alkyl radicals, which react with dioxygen to afford alkylperoxyl radicals. Alkylperoxyl radicals abstract hydrogen atoms from alkanes to yield alkyl hydroperoxides, accompanied by regeneration of alkyl radicals to constitute the radical chain reactions, so called autoxidation. The radical chain is terminated in the bimolecular reactions of alkylperoxyl radicals to yield the corresponding alcohols and ketones. DDQ(?-) , produced by the photoinduced electron transfer from alkanes to the excited state of DDQ, disproportionates with protons to yield DDQH2 . PMID- 27399907 TI - Benchmarking the Predictive Power of Ligand Efficiency Indices in QSAR. AB - Compound physicochemical properties favoring in vitro potency are not always correlated to desirable pharmacokinetic profiles. Therefore, using potency (i.e., IC50) as the main criterion to prioritize candidate drugs at early stage drug discovery campaigns has been questioned. Yet, the vast majority of the virtual screening models reported in the medicinal chemistry literature predict the biological activity of compounds by regressing in vitro potency on topological or physicochemical descriptors. Two studies published in this journal showed that higher predictive power on external molecules can be achieved by using ligand efficiency indices as the dependent variable instead of a metric of potency (IC50) or binding affinity (Ki). The present study aims at filling the shortage of a thorough assessment of the predictive power of ligand efficiency indices in QSAR. To this aim, the predictive power of 11 ligand efficiency indices has been benchmarked across four algorithms (Gradient Boosting Machines, Partial Least Squares, Random Forest, and Support Vector Machines), two descriptor types (Morgan fingerprints, and physicochemical descriptors), and 29 data sets collected from the literature and ChEMBL database. Ligand efficiency metrics led to the highest predictive power on external molecules irrespective of the descriptor type or algorithm used, with an R(2)test difference of ~0.3 units and a this difference ~0.4 units when modeling small data sets and a normalized RMSE decrease of >0.1 units in some cases. Polarity indices, such as SEI and NSEI, led to higher predictive power than metrics based on molecular size, i.e., BEI, NBEI, and LE. LELP, which comprises a polarity factor (cLogP) and a size parameter (LE) constantly led to the most predictive models, suggesting that these two properties convey a complementary predictive signal. Overall, this study suggests that using ligand efficiency indices as the dependent variable might be an efficient strategy to model compound activity. PMID- 27399913 TI - Erratum. PMID- 27399911 TI - Effect of oxygen on the per-cell extracellular electron transfer rate of Shewanella oneidensis MR-1 explored in bioelectrochemical systems. AB - Extracellular electron transfer (EET) is a mechanism that enables microbes to respire solid-phase electron acceptors. These EET reactions most often occur in the absence of oxygen, since oxygen can act as a competitive electron acceptor for many facultative microbes. However, for Shewanella oneidensis MR-1, oxygen may increase biomass development, which could result in an overall increase in EET activity. Here, we studied the effect of oxygen on S. oneidensis MR-1 EET rates using bioelectrochemical systems (BESs). We utilized optically accessible BESs to monitor real-time biomass growth, and studied the per-cell EET rate as a function of oxygen and riboflavin concentrations in BESs of different design and operational conditions. Our results show that oxygen exposure promotes biomass development on the electrode, but significantly impairs per-cell EET rates even though current production does not always decrease with oxygen exposure. Additionally, our results indicated that oxygen can affect the role of riboflavin in EET. Under anaerobic conditions, both current density and per-cell EET rate increase with the riboflavin concentration. However, as the dissolved oxygen (DO) value increased to 0.42 mg/L, riboflavin showed very limited enhancement on per cell EET rate and current generation. Since it is known that oxygen can promote flavins secretion in S. oneidensis, the role of riboflavin may change under anaerobic and aerobic conditions. Biotechnol. Bioeng. 2017;114: 96-105. (c) 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID- 27399914 TI - Computational and molecular analysis of conserved influenza A virus RNA secondary structures involved in infectious virion production. AB - As well as encoding viral proteins, genomes of RNA viruses harbor secondary and tertiary RNA structures that have been associated with functions essential for successful replication and propagation. Here, we identified stem-loop structures that are extremely conserved among 1,884 M segment sequences of influenza A virus (IAV) strains from various subtypes and host species using computational and evolutionary methods. These structures were predicted within the 3' and 5' ends of the coding regions of M1 and M2, respectively, where packaging signals have been previously proposed to exist. These signals are thought to be required for the incorporation of a single copy of 8 different negative-strand RNA segments (vRNAs) into an IAV particle. To directly test the functionality of conserved stem-loop structures, we undertook reverse genetic experiments to introduce synonymous mutations designed to disrupt secondary structures predicted at 3 locations and found them to attenuate infectivity of recombinant virus. In one mutant, predicted to disrupt stem loop structure at nucleotide positions 219-240, attenuation was more evident at increased temperature and was accompanied by an increase in the production of defective virus particles. Our results suggest that the conserved secondary structures predicted in the M segment are involved in the production of infectious viral particles during IAV replication. PMID- 27399915 TI - Extremely Stable Supramolecular Hydrogels Assembled from Nonionic Peptide Amphiphiles. AB - Peptide hydrogels with high stability in different media are of great interest in biomedical applications. In this paper, we report an easy, fast, and scalable method for preparing a family of nonionic peptide amphiphiles (PAs) obtained by direct aminolysis of alkyl-oilgo(gamma-benzyl-l-glutamate) samples, which were synthesized via the alkyl amine-initiated sequence ring-opening reaction of alpha amino acid N-carboxyanhydrides. One great advantage of this method is that vast chemical diversity and large-scale yields can be achieved easily using commercially available hydramines. These PA samples can readily form a clear hydrogel without any external aid and show exceptionally enhanced gelation properties with a critical gelation concentration as low as 0.05 wt %. The hydrogels are highly stable against extreme pH values of 1 and 14 and a high salt concentration of 200 mM NaCl. These properties combined with the shear-thinning properties make these PA hydrogels ideal candidates for the new generation of injectable scaffolds. PMID- 27399917 TI - Expression of the chemokine CXCL14 and cetuximab-dependent tumour suppression in head and neck squamous cell carcinoma. AB - Cetuximab, a monoclonal antibody against the epidermal growth factor receptor (EGFR), has been successfully used to treat some patients with colorectal cancer and those with head and neck squamous cell carcinoma (HNSCC). For the effective treatment, it is essential to first identify cetuximab-responsive patients. The level of EGFR expression and/or the presence of mutations in signalling molecules downstream of the EGFR pathway have been reported to be determining factors for cetuximab responsiveness in colorectal cancer patients; however, limited data have been reported for HNSCC patients. We previously reported that the chemokine CXCL14 exhibits tumour-suppressive effects against xenografted HNSCC cells, which may be classified into two groups, CXCL14-expressing and non-expressing cells under serum-starved culture conditions. Here we employed CXCL14-expressing HSC-3 cells and CXCL14-non-expressing YCU-H891 cells as representatives of the two groups and compared their responses to cetuximab and their CXCL14 expression under various conditions. The growth of xenografted tumours initiated by HSC-3 cells, which expressed CXCL14 in vivo and in vitro, was suppressed by the injection of cetuximab into tumour-bearing mice; however, neither the expression of the chemokine nor the cetuximab-dependent suppression of xenograft tumour growth was observed for YCU-H891 cells. Both types of cells expressed EGFR and neither type harboured mutations in signalling molecules downstream of EGFR that have been reported in cetuximab-resistant colon cancer patients. The inhibition of the extracellular signal-regulated kinase (ERK) signalling increased the levels of CXCL14 messenger RNA (mRNA) in HSC-3 cells, but not in YCU-H891 cells. We also observed that the CXCL14 promoter region in YCU-H891 cells was hypermethylated, and that demethylation of the promoter by treatment with 5-aza 2'-deoxycytidine restored CXCL14 mRNA expression and in vivo cetuximab-mediated tumour growth suppression. Finally, we observed in vivo tumour growth suppression when YCU-H891 cells were engineered to express CXCL14 ectopically in the presence of doxycycline. These results indicate that CXCL14 expression may be a good predictive biomarker for cetuximab-dependent tumour suppression. PMID- 27399918 TI - miR-1260b is a Potential Prognostic Biomarker in Colorectal Cancer. AB - BACKGROUND Colorectal cancer (CRC) mainly refers to colon and rectum cancer, which is the most common gastrointestinal malignant tumor. MicroRNAs (miRNAs) in tumors participate in multiple processes of malignancy development, including cell differentiation, proliferation, invasion, and metastasis. In this study we explored the relationship of miR-1260b abnormal expression with clinical pathological features in CRC patients. MATERIAL AND METHODS The expression of miR 1260b was detected by real-time quantitative polymerase chain reaction (real-time PCR) in 120 cases of CRC tissues. The correlation of miR-1260b expression with the clinicopathologic features of CRC was analyzed by SPSS 21.0 statistical software. The Kaplan-Meier method was used for survival analysis. Cox regression analyses were conducted to determine whether miR-1260b was an independent predictor of survival for CRC patients. RESULTS The miR-1260b expression in CRC was significantly higher than the expression levels in the corresponding para carcinoma tissues (P<0.001). According to the expression levels of miR-1260b, 120 cases of CRC patients were classified into either the miR-1260b high expression group or the miR-1260b low expression group. The high expression levels of miR 1260b in CRC patients was associated with lymph node metastasis (P<0.05) and venous invasion (P<0.001). However, the high miR-1260b expression had no significant correlation with other clinical parameters (P>0.05). The high miR 1260b expression patients survived for shorter times than those CRC patients with low miR-1260b expression (P<0.05). Multivariate analysis revealed that high miR 1260b means poor prognosis of patients with CRC. CONCLUSIONS The high expression level of miR-1260b is an independent prognostic biomarker that indicates a worse prognosis for patients with CRC. PMID- 27399916 TI - Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death. AB - Here, we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig pressure-overload model by integrated multiome analysis. Relative protein abundances from sham-operated HYP and HF hearts were assessed by iTRAQ LC-MS/MS. Metabolites were quantified by LC-MS/MS or GC-MS. Transcriptome profiles were obtained using mRNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation, and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial procsses, were downregulated in HF but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, acylcarnitines were downregulated in HYP and fatty acids accumulated in HF. The correlation of transcript and protein changes in HF was weak (R(2) = 0.23), suggesting post-transcriptional gene regulation in HF. Proteome/metabolome integration indicated metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. On the basis of these findings, we present a model of cardiac decompensation involving impaired nuclear integration of Ca(2+) and cyclic nucleotide signals that are coupled to mitochondrial metabolic and antioxidant defects through the CREB/PGC1alpha transcriptional axis. PMID- 27399920 TI - Separate capacities for storing different features in visual working memory. AB - Recent empirical and theoretical work suggests that visual features such as color and orientation can be stored or retrieved independently in visual working memory (VWM), even in cases when they belong to the same object. Yet it remains unclear whether different feature dimensions have their own capacity limits, or whether they compete for shared but limited resources in VWM. In 3 experiments, participants memorized arrays of dual-feature objects, for which the number of feature values was fixed on one feature dimension and was varied on the other feature dimension. The results show that memory performance on the fixed dimension was not affected by the number of to-be-stored feature values on the other. These findings provide converging evidence that visual features can be encoded and stored separately in VWM if the task requires it, with each having its own capacity limit and little cross-dimensional interference. (PsycINFO Database Record PMID- 27399919 TI - Intrinsic versus Extrinsic Aging: A Histopathological, Morphometric and Immunohistochemical Study of Estrogen Receptor beta and Androgen Receptor. AB - Skin is a target organ of sex steroids which play important roles in skin health and disease. The aim of this study is to investigate the expression of estrogen receptor beta (ERbeta) and androgen receptor (AR) in human skin from different age groups for a better understanding of the hormonal regulation of skin aging. Using standard immunohistochemical techniques, biopsies of sun-unprotected and sun-protected skin were taken from 60 normal subjects. Sun-protected skin showed significantly higher immunoreactivity for ERbeta and AR compared to sun unprotected skin of all age groups. Significantly higher ERbeta H score and percent of expression were associated with the 20-35 years age group compared to the groups that were 35-50 years and >50 years old (p < 0.02, p = 0.03, respectively) in sun-unprotected and sun-protected skin (p < 0.001, p = 0.01, respectively). AR H score showed a negative correlation with age (p = 0.04) with no significant difference in immunoreactivity in different age groups, either in sun-unprotected or sun-protected skin. There was also a significant correlation between ERbeta H score and epidermal thickness in sun-unprotected (p = 0.04) and sun-protected skin (p = 0.04) in studied subjects regardless of age. The same relationships did not reach significance with AR expression. However, a significant positive correlation was detected between H scores and percent of expression of ERbeta and AR in sun-unprotected (p = 0.01, p = 0.02, respectively) and sun-protected skin (p = 0.005, p = 0.02, respectively) regardless of age. In conclusion, both ERbeta and AR decline gradually with intrinsic and extrinsic aging. This decline is more obvious with extrinsic aging. Further large-scaled studies are recommended to expand, validate and translate current findings to clinically significant, diagnostic and therapeutic applications. Molecular studies to investigate the probable ligand-independent action of both receptors are warranted. In addition, their gene expression patterns and associated signaling and metabolic pathways can also be tackled to provide a basis for further interventions in pathological processes that involve their dysregulation. PMID- 27399921 TI - Factors Associated with Abortion in Women of Reproductive Age. AB - Purpose To verify sociodemographic factors associated with the occurrence of abortion in women of reproductive age, in areas covered by the Family Health Strategy (FHS), a program from the Brazilian Ministry of Health. Methods A cross sectional study using household surveys of 350 women aged 15 to 49. The report of abortion was a variable indicator, and sociodemographic aspects were covariables. Prevalence ratio (PR) and respective 95% confidence intervals were used to estimate the magnitude of the associations. Results There were associations among age, civil status, race/color, and religion; an increase in the prevalence of lower levels of education, age less than 20, and student status were protective factors. Conclusion The association between sociodemographic characteristics and the report of abortion is attributed to the fact that there is a lack at the FHS in the availability of fundamental healthcare services for young women; these findings call for action to guarantee the access to information about contraceptives and guidance to decrease the risk of unplanned pregnancies and abortions. PMID- 27399922 TI - EZH2 Protein Expression and Tumor Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer. AB - Introduction Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. However, some tumors will not respond to this treatment due to histological and molecular features. The protein EZH2 (enhancer of zest homolog 2) is a histone methyltransferase that is correlated with poorly differentiated breast carcinomas and aggressive tumor behavior. Purpose The present study evaluated the association between EZH2 expression and response to NAC, and its correlation with HER2 overexpression, estrogen and progesterone receptors (ER, PR) and Ki-67 proliferation index. Methods A total of 60 patients with locally advanced breast cancer treated with NAC were selected for this study. Twenty-three paraffin blocks had not enough material for tissue resection, and were not evaluated. A tissue microarray based in immunohistochemistry (IHC) analysis of EZH2 was performed for the remaining 37 specimens. Patients were divided into two groups based on response to NAC. Results EZH2 expression was significantly associated with markers of poor prognosis such as ER negativity (p = 0.001), PR negativity (p = 0.042) and high Ki-67 proliferation index (p = 0.002). High EZH2 expression was not correlated with the response to NAC. Conclusions Our data suggested that EZH2 protein expression may not correlate with the clinical response to NAC. Other studies with more patients are needed to confirm this observation. PMID- 27399923 TI - Betatrophin Levels were Increased in Pregnant Women with or without Gestational Diabetes Mellitus and Associated with Beta Cell Function. AB - Purpose betatrophin has been reported to boost beta cell expansion in insulin resistant states. Pregnancy is a well-recognized physiological state of insulin resistance. Betatrophin levels in pregnant women and their relationships with metabolic variables remain to be elucidated. Methods A total of 49 pregnant women and 31 age-matched unpregnant women with normal glucose regulation (UP-NGR) were included. Among these subjects, according to results from 75 g oral glucose tolerance test (OGTT), 22 women were diagnosed as having gestational diabetes mellitus (GDM). Results Our study found that pregnant women, regardless of their glucose regulation status, had remarkably higher triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA beta). However, GDM patients had much lower HOMA-beta compared with those of pregnant women with normal glucose regulation (P-NGR). Participants of the P-NGR group had almost 4 times higher levels of betatrophin than those of the UP-NGR group. Although betatrophin levels were lower in the GDM group than those of the P-NGR group, the difference did not reach statistical significance. Spearman correlation analysis showed that betatrophin levels were positively and significantly associated with total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), FINS and HOMA-beta. However, adjustments of TC, TG and HDL-c eliminated the association between HOMA-beta and betatrophin. Conclusions Pregnant women have significantly higher betatrophin levels in comparison to unpregnant women. Betatrophin levels are positively and significantly associated with beta cell function and lipid levels. Furthermore, lipids may contribute to the association between betatrophin and beta cell function. PMID- 27399924 TI - Depressive Symptoms in Pregnancy: The Influence of Social, Psychological and Obstetric Aspects. AB - Purpose To assess the prevalence of depressive symptoms and their association with social, psychological, behavioral and obstetric characteristics in pregnant women. Methods This is a cross-sectional study. The sample consisted of 375 pregnant women who attended prenatal clinics in two public maternity hospitals located in the city of Goiania, Brazil. To testify the depressive symptoms, we used the Hospital Anxiety and Depression Scale (HADS). A descriptive statistical analysis was performed using programs such as CDC EPI-INFOTM, version 7.1.5, and Statistical Package for Social Sciences (IBM SPSS), version 21.0. Results the patients had probable depressive symptoms (15.47%) and possible depressive symptoms (25.33%). The bivariate analysis showed a significant association among "depressive symptoms" and the following variables: "single or divorced" (prevalence ratio, PR = 2.08; 95% confidence interval, CI = 1.26 to 3.44); "physical activity during pregnancy" (PR = 3.96; 95%CI = 1.28 to 12.31); exposure to "psychological/emotional" violence (PR = 4.74; 95%CI = 2.94 to 7.64); "prior mental problem" (PR = 2.66; 95%CI =1.49 to 4.73) and "obstetric complications during pregnancy" (PR = 2.53; 95%CI = 1.55 to 4.13). The multivariate analysis confirmed the association of these depressive symptoms with the variables "suffered psychological/emotional violence" (odds ratio, OR = 5.821; 95%CI = 2.939 to 11.528); "physical activity during pregnancy" (OR = 3.885; 95%CI = 1.060 to 14.231); "obstetric complications during pregnancy" (OR = 2.442; 95%CI = 1.233 to 4.834) and "single or divorced" (OR = 2.943; 95%CI = 1.326 to 6.533). Conclusions the prevalence of depressive symptoms among pregnant women is of 15.47%, and emotional violence is the main factor associated with gestational depression. PMID- 27399925 TI - Selective Episiotomy: Indications, Techinique, and Association with Severe Perineal Lacerations. AB - Introduction Episiotomy is a controversial procedure, especially because the discussion that surrounds it has gone beyond the field of scientific debate, being adopted as an indicator of the "humanization of childbirth". The scientific literature indicates that episiotomy should not be performed routinely, but selectively. Objectives To review the literature in order to assess whether the implementation of selective episiotomy protects against severe perineal lacerations, the indications for the procedure, and the best technique to perform it. Methods A literature search was performed in PubMed using the terms episiotomy or perineal lacerations, and the filter clinical trial. The articles concerning the risk of severe perineal lacerations with or without episiotomy, perineal protection, or episiotomy techniques were selected. Results A total of 141 articles were identified, and 24 of them were included in the review. Out of the 13 studies that evaluated the risk of severe lacerations with and without episiotomy, 5 demonstrated a protective role of selective episiotomy, and 4 showed no significant differences between the groups. Three small studies confirmed the finding that episiotomy should be performed selectively and not routinely, and one study showed that midline episiotomy increased the risk of severe lacerations. The most cited indications were primiparity, fetal weight greater than 4 kg, prolonged second stage, operative delivery, and shoulder dystocia. As for the surgical technique, episiotomies performed with wider angles (> 40 degrees ) and earlier in the second stage (before "crowning ") appeared to be more protective. Conclusions Selective episiotomy decreases the risk of severe lacerations when compared with the non-performance or the performance of routine episiotomy. The use of a proper surgical technique is fundamental to obtain better results, especially in relation to the angle of incision, the distance from the vaginal introitus, and the correct timing for performing the procedure. Not performing the episiotomy when indicated or not applying the correct technique may increase the risk of severe perineal lacerations. PMID- 27399926 TI - Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome. AB - Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases. PMID- 27399927 TI - Zika Virus Infection in Pregnant Women: Topic for Discussion. PMID- 27399928 TI - Engineering a Dual-Layer Chitosan-Lactide Hydrogel To Create Endothelial Cell Aggregate-Induced Microvascular Networks In Vitro and Increase Blood Perfusion In Vivo. AB - Here, we report the use of chemically cross-linked and photo-cross-linked hydrogels to engineer human umbilical vein endothelial cell (HUVEC) aggregate induced microvascular networks to increase blood perfusion in vivo. First, we studied the effect of chemically cross-linked and photo-cross-linked chitosan lactide hydrogels on stiffness, degradation rates, and HUVEC behaviors. The photo cross-linked hydrogel was relatively stiff (E = ~15 kPa) and possessed more compact networks, denser surface texture, and lower enzymatic degradation rates than the relatively soft, chemically cross-linked hydrogel (E = ~2 kPa). While both hydrogels exhibited nontoxicity, the soft chemically cross-linked hydrogels expedited the formation of cell aggregates compared to the photo-cross-linked hydrogels. Cells on the less stiff, chemically cross-linked hydrogels expressed more matrix metalloproteinase (MMP) activity than the stiffer, photo-cross-linked hydrogel. This difference in MMP activity resulted in a more dramatic decrease in mechanical stiffness after 3 days of incubation for the chemically cross-linked hydrogel, as compared to the photo-cross-linked one. After determining the physical and biological properties of each hydrogel, we accordingly engineered a dual-layer hydrogel construct consisting of the relatively soft, chemically cross linked hydrogel layer for HUVEC encapsulation, and the relatively stiff, acellular, photo-cross-linked hydrogel for retention of cell-laden microvasculature above. This dual-layer hydrogel construct enabled a lasting HUVEC aggregate-induced microvascular network due to the combination of stable substrate, enriched cell adhesion molecules, and extracellular matrix proteins. We tested the dual-layer hydrogel construct in a mouse model of hind-limb ischemia, where the HUVEC aggregate-induced microvascular networks significantly enhanced blood perfusion rate to ischemic legs and decreased tissue necrosis compared with both no treatment and nonaggregated HUVEC-loaded hydrogels within 2 weeks. This study suggests an effective means for regulating hydrogel properties to facilitate a stable, HUVEC aggregate-induced microvascular network for a variety of vascularized tissue applications. PMID- 27399929 TI - Yellow Fever Virus: Cause for Concern or Alarm? PMID- 27399930 TI - Investigation of alpha-Thioglycoside Donors: Reactivity Studies toward Configuration-Controlled Orthogonal Activation in One-Pot Systems. AB - The influence of anomeric configuration upon thioglycoside donors remains relatively unexplored. Utilizing methodology developed for the stereoselective and high-yielding synthesis of alpha-glycosyl thiols, a series of alpha thioglycosides were synthesized, and their reactivity was compared to that of their beta-counterparts. The highly selective activation observed for anomeric pairs containing a 2-O-acyl moiety and additional findings are reported. Application of a pair of "superarmed" thioglycosides to a one-pot oligosaccharide system is also described, in which selectivity is a result of configuration-based orthogonal activation. PMID- 27399931 TI - Bright Electrogenerated Chemiluminescence of a Bis-Donor Quadrupolar Spirofluorene Dye and Its Nanoparticles. AB - A series of symmetric fluorescent dyes built from a spirofluorene core bearing electroactive end groups and having different conjugated linkers were prepared with a view to their use as building blocks for the preparation of electrochemiluminescent (ECL) dyes and nanoparticles. Their electrochemical, spectroelectrochemical, and ECL properties were first investigated in solution, and structure/activity relationships were derived. The electrochemical and ECL properties show drastic variation that could be tuned by means of the nature of the pi-conjugated system, the end groups, and the core. In this series, highly fluorescent dye 1 based on a spirofluorene core and triphenylamine end groups connected via thiophene moieties shows the most promising and intriguing properties. Dye 1 is reversibly oxidized in three well-separated steps and generates a very intense and large ECL signal. Its ECL efficiency is 4.5 times higher than that of the reference compound [Ru(bpy)3 ](2+) (bpy=2,2'-bipyridine). This remarkably high efficiency is due to the very good stability of the higher oxidized states and it makes 1 a very bright organic ECL luminophore. In addition, thanks to its molecular structure, this dye retains fluorescence after nanoprecipitation in water, which leads to fluorescent organic nanoparticles (FONs). The redox behavior of these FONs shows oxidation waves consistent with the initial molecular species. Finally, ECL from FONs made of 1 was recorded in water and strong ECL nanoemitters are thus obtained. PMID- 27399932 TI - A comprehensive meta-analysis of cognitive-behavioral interventions for social anxiety disorder in children and adolescents. AB - The effectiveness of different types of CBT for children and adolescents suffering from Social Anxiety Disorder (SAD) is generally supported. However, no systematic efforts have been made to quantitatively summarize and analyse the impact of specific variables on therapeutic outcome. Here, we assessed the magnitude and duration of CBT effectiveness in children and adolescents with SAD. The effectiveness of CBT was supported by the effect sizes of studies that had examined pre-post (g=0.99), between-group (g=0.71), and follow-up responses (follow-up vs. pre-test mean g=1.18, follow-up vs. post-test mean g=0.25). A significant moderating effect was found for the variable "number of treatment sessions". In addition, larger effect sizes were found in studies that included "Social Skills Training" sessions in the intervention package. Data support the effectiveness of CBT interventions and its durability for SAD in children and adolescents. Adding social skills training to the intervention package can further enhance the impact of treatment. PMID- 27399933 TI - Neonatal respiratory distress syndrome: are risk factors the same in preterm and term infants? AB - OBJECTIVE: To analyze respiratory distress syndrome (RDS) incidence and risk factors at different gestational age. METHODS: We considered data from 321 327 infants born in Lombardy, a Northern Italian Region. We computed multivariate analysis to identify risk factors for RDS by dividing infants in early- and moderate-preterm, late-preterm and term infants. RESULTS: Low-birth weight is the main risk factor for RDS, with higher odds ratio in term births. The risk was higher in infants delivered by cesarean section and in male, for all gestational age. Pathological course of pregnancy resulted in increased risk only in late preterm and term infants. Maternal age and multiple birth were not associated with increased risk in any group. Babies born at term after assisted conception were at higher risk of RDS. CONCLUSION: Our analysis suggests as some risk factors do not influence RDS incidence in the same way at different gestational age. PMID- 27399934 TI - A Nanostructured Bifunctional platform for Sensing of Glucose Biomarker in Artificial Saliva: Synergy in hybrid Pt/Au surfaces. AB - We report on a bimetallic, bifunctional electrode where a platinum (Pt) surface was patterned with nanostructured gold (Au) fingers with different film thicknesses, which was functionalized with glucose oxidase (GOx) to yield a highly sensitive glucose biosensor. This was achieved by using selective adsorption of a self-assembled monolayer (SAM) onto Au fingers, which allowed GOx immobilization only onto the Au-SAM surface. This modified electrode was termed bifunctional because it allowed to simultaneously immobilize the biomolecule (GOx) on gold to catalyze glucose, and detect hydrogen peroxide on Pt sites. Optimized electrocatalytic activity was reached for the architecture Pt/Au SAM/GOx with 50nm thickness of Au, where synergy between Pt and Au allowed for detection of hydrogen peroxide (H2O2) at a low applied potential (0V vs. Ag/AgCl). Detection was performed for H2O2 in the range between 4.7 and 102.7 nmol L(-1), with detection limit of 3.4*10(-9) mol L(-1) (3.4 nmol L(-1)) and an apparent Michaelis-Menten rate constant of 3.2*10(-6)molL(-1), which is considerably smaller than similar devices with monometallic electrodes. The methodology was validated by measuring glucose in artificial saliva, including in the presence of interferents. The synergy between Pt and Au was confirmed in electrochemical impedance spectroscopy measurements with an increased electron transfer, compared to bare Pt and Au electrodes. The approach for fabricating the reproducible bimetallic Pt/Au electrodes is entirely generic and may be explored for other types of biosensors and biodevices where advantage can be taken of the combination of the two metals. PMID- 27399935 TI - Impedimetric antimicrobial peptide-based sensor for the early detection of periodontopathogenic bacteria. AB - Peri-implantitis, an inflammation caused by biofilm formation, constitutes a major cause of implant failure in dentistry. Thus, the detection of bacteria at the early steps of biofilm growth represents a powerful strategy to prevent implant-related infections. In this regard, antimicrobial peptides (AMPs) can be used as effective biological recognition elements to selectively detect the presence of bacteria. Thus, the aim of the present study was to combine the use of miniaturized and integrated impedimetric transducers and AMPs to obtain biosensors with high sensitivity to monitor bacterial colonization. Streptococcus sanguinis, which is one of the most prevalent strains in the onset of periodontal diseases, was used as a model of oral bacteria. To this end, a potent AMP derived from human lactoferrin was synthesized and covalently immobilized on interdigitated electrode arrays (IDEA). X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS) were employed to optimize and characterize the method of immobilization. Noteworthy, the interaction of Streptococcus sanguinis with AMP-coated sensors provoked significant changes in the impedance spectra, which were univocally associated with the presence of bacteria, proving the feasibility of our method. In this regard, the developed biosensor permits to detect the presence of bacteria at concentrations starting from 10(1) colony forming units (CFU)mL(-1) in KCl and from 10(2) CFUmL(-1) in artificial saliva. Moreover, the system was devoid of cytotoxicity for human fibroblasts. These results indicate that the proposed approach can be effective in the detection of initial stages of biofilm formation, and may be useful in the early prevention and treatment of peri-implantitis. PMID- 27399936 TI - Robust Multicolor Single Photon Emission from Point Defects in Hexagonal Boron Nitride. AB - Hexagonal boron nitride (hBN) is an emerging two-dimensional material for quantum photonics owing to its large bandgap and hyperbolic properties. Here we report two approaches for engineering quantum emitters in hBN multilayers using either electron beam irradiation or annealing and characterize their photophysical properties. The defects exhibit a broad range of multicolor room-temperature single photon emissions across the visible and the near-infrared spectral ranges, narrow line widths of sub-10 nm at room temperature, and a short excited-state lifetime, and high brightness. We show that the emitters can be categorized into two general groups, but most likely possess similar crystallographic structure. Remarkably, the emitters are extremely robust and withstand aggressive annealing treatments in oxidizing and reducing environments. Our results constitute a step toward deterministic engineering of single emitters in 2D materials and hold great promise for the use of defects in boron nitride as sources for quantum information processing and nanophotonics. PMID- 27399937 TI - Two new sesquiterpenes from Chloranthus japonicus Sieb. AB - Two new sesquiterpenes, namely, 1beta,10beta-dihydroxy-eremophil-7(11), 8-dien 12,8-olide (1) and 8,12-epoxy-1beta-hydroxyeudesm-3,7,11-trien-9-one (2), together with three known sesquiterpenoids, shizukolidol (3), 4alpha-hydroxy 5alpha(H)-8beta-methoxy-eudesm-7(11)-en-12,8-olide (4), and neolitacumone B (5), and two known monoterpenes, (3R,4S,6R)-p-menth-1-en-3,6-diol (6) and (R)-p-menth 1-en-4,7-diol (7), were isolated from the whole plant of Chloranthus japonicus Sieb. Their structures were elucidated on the basis of spectroscopic data analysis and comparison with those of related known compounds. Compounds 4-7 were isolated from this plant for the first time. PMID- 27399938 TI - Polybrominated Diphenyl Ethers: Structure Determination and Trends in Antibacterial Activity. AB - Antibacterial-guided fractionation of the Dictyoceratid sponges Lamellodysidea sp. and two samples of Dysidea granulosa yielded 14 polybrominated, diphenyl ethers including one new methoxy-containing compound (8). Their structures were elucidated by interpretation of spectroscopic data of the natural product and their methoxy derivatives. Most of the compounds showed strong antimicrobial activity with low- to sub-microgram mL(-1) minimum inhibitory concentrations against drug-susceptible and drug-resistant strains of Staphylococcus aureus and Enterococcus faecium, and two compounds inhibited Escherichia coli in a structure dependent manner. PMID- 27399939 TI - Asymmetry and Maldistribution of Polyacrylamide Hydrogel Filler in the Infraorbital Area Successfully Managed With Botulinum Toxin A Treatment. PMID- 27399940 TI - The Role of Elastic Fibers in Scar Formation and Treatment. AB - BACKGROUND: Laser therapy is a continuously evolving treatment option for scars, and the underlying therapeutic mechanisms continue to be elucidated. OBJECTIVE: To comprehensively review the literature to summarize the role of elastin in the formation scars, as well as treatment via therapeutic lasers. METHODS: Review of the PubMED/MEDLINE database for available studies pertaining to the role of elastic fibers in scar formation and after laser-based therapy. RESULTS: The loss and disorganization of elastic fiber components plays a role in the development of atrophic, hypertrophic, and keloid scars. While the majority of histologic studies focus on the underlying changes in collagen, neoelastogenesis and reorganization of elastic fibers have also been demonstrated in studies using ablative, nonablative, and fractional laser devices for the treatment of scars. CONCLUSION: Production of novel elastin and normalization of elastic fiber organization occur after a variety of resurfacing procedures to treat scarring. As the treatment modalities to manage scars continue to evolve, further characterization of the role of elastin in the skin and in scar formation is merited. PMID- 27399941 TI - Use of Epidermal Grafting for Treatment of Depigmented Skin in Piebaldism. PMID- 27399942 TI - Incidental Intravascular Histiocytosis During Mohs Surgery. PMID- 27399943 TI - Plaque-Like Atypical Fibroxanthoma, A Rare Invasive Variant. PMID- 27399944 TI - Tricks and Tips for Manual Dermabrasion. PMID- 27399946 TI - Deep Venous Thrombosis and Pulmonary Embolism Following Outpatient Dermatologic Surgery. PMID- 27399947 TI - Management of Chondrodermatitis Nodularis Helicis: A Systematic Review and Treatment Algorithm. AB - BACKGROUND: Chondrodermatitis nodularis helicis (CNH) is an idiopathic benign inflammatory painful condition of the ear. Still, to date, no study has yet evaluated nor compared treatments regarding their safety and efficacy. OBJECTIVE: The objective of this study is to review all available treatment modalities of CNH that were described in the literature, compare their efficacy and propose a treatment algorithm. METHODS AND MATERIALS: A systematic review of the literature was conducted using Embase, Medline, and Cochrane databases. Articles studying the management of CNH that reported data on the cure rates were included in this review. RESULTS: A total of 29 studies were included in the review. The 3 most commonly reported treatments for CNH are surgery, pressure relief, and topical nitroglycerin. Surgery has higher cure rate (82%) compared with pressure relief treatment (37%) or nitroglycerin (51%) (p < .0001). Surgery should be considered as the first-line treatment for CNH. Second-line treatments include nonsurgical therapies, particularly nitroglycerin and pressure relief techniques, alone or in combination. Third-line treatments include newer or less studied methods. CONCLUSION: Among the treatment modalities, surgery showed the highest cure rates. Adequately designed randomized controlled trials are warranted to compare newer therapeutic methods. PMID- 27399949 TI - Through and Through Defect on the Helix and Antihelix. PMID- 27399948 TI - Permanent Injectable Polyacrylamide Hydrogel Dermal Filler for a Large Subcutaneous Defect Secondary to Lupus Panniculitis. PMID- 27399950 TI - Therapeutic Use of Hyaluronic Acid Fillers in the Treatment of Corticosteroid Induced Skin and Subcutaneous Atrophy. PMID- 27399951 TI - Repair of Full-Thickness Loss of the Upper Ear. PMID- 27399952 TI - Recovery After Matrix Shave Biopsy. PMID- 27399953 TI - The Accuracy of Ultrasonography on Location of Lipomas in Forehead. PMID- 27399954 TI - Chlorhexidine Keratitis: Safety of Chlorhexidine as a Facial Antiseptic. AB - BACKGROUND: Effective antiseptic to reduce surgical site infections is a cornerstone of modern surgery. Chlorhexidine gluconate-based antiseptics are among the most effective of these products. Unfortunately, chlorhexidine solutions are toxic to the cornea and middle ear, and they pose a splash risk to both the patient and health care personnel. OBJECTIVE: To examine the clinical evidence that led to the disavowal of chlorhexidine antiseptic solution for use on the face and head. METHODS AND MATERIALS: Reference searches were performed using PubMed, Embase, and LexisNexis databases without restriction to the date of publication, language, or study setting. RESULTS: The literature revealed 11 sentinel cases of severe chlorhexidine-related keratitis in the late 1980s. These cases are reviewed together with data on ototoxicity and alternative products to understand why chlorhexidine solution should not be used on the face and scalp. CONCLUSION: Chlorhexidine antiseptic solutions are highly effective. However, they pose a risk to the middle ear and have the potential to irreversibly damage the cornea with a minimal splash exposure. Povidone-iodine is a safe and effective alternative. PMID- 27399955 TI - Commentary on Cost of Actinic Keratoses and Skin Cancers. PMID- 27399956 TI - A Randomized, Comparative Study to Evaluate Efficacy and Safety of Two Injection Volumes of AbobotulinumtoxinA in Treatment of Glabellar Lines. AB - BACKGROUND: Different volumes of 0.9% NaCl may be used to reconstitute abobotulinumtoxinA yielding an injection volume that ranges from 0.05 to 0.1 mL per injection point for treatment of glabellar lines. OBJECTIVE: To evaluate the efficacy, safety, and subject satisfaction of 2 different injection volumes to deliver the same unit dose of abobotulinumtoxinA for treatment of glabellar lines. MATERIALS AND METHODS: This randomized comparative study was conducted using 2 different reconstitution volumes to deliver a fixed unit dose of 10 Speywood units (sU) of abobotulinumtoxinA in either 0.05 mL (labeled volume) or 0.1 mL (twofold volume) per injection point. Evaluations included wrinkle severity, neurophysiological assessment by compound muscle action potential (CMAP), and subject satisfaction. RESULTS: Use of either injection volume of abobotulinumtoxinA resulted in the early onset of effect, high effectiveness, and long duration of effect. The safety profile and injection pain levels were similar in both groups. The twofold injection volume was shown to be noninferior to the labeled injection volume based on CMAP results. CONCLUSION: A twofold increase in injection volume to 0.1 mL per injection point to deliver 10 sU of abobotulinumtoxinA is effective and safe. PMID- 27399957 TI - Heterogeneity in testing practices for infections during pregnancy: national survey across Switzerland. AB - QUESTION: Detection and treatment of infections during pregnancy are important for both maternal and child health. The objective of this study was to describe testing practices and adherence to current national guidelines in Switzerland. METHODS: We invited all registered practicing obstetricians and gynaecologists in Switzerland to complete an anonymous web-based questionnaire about strategies for testing for 14 infections during pregnancy. We conducted a descriptive analysis according to demographic characteristics. RESULTS: Of 1138 invited clinicians, 537 (47.2%) responded and 520 (45.6%) were eligible as they are currently caring for pregnant women. Nearly all eligible respondents tested all pregnant women for group B streptococcus (98.0%), hepatitis B virus (HBV) (96.5%) and human immunodeficiency virus (HIV) (94.7%), in accordance with national guidelines. Although testing for toxoplasmosis is not recommended, 24.1% of respondents tested all women and 32.9% tested at the request of the patient. Hospital doctors were more likely not to test for toxoplasmosis than doctors working in private practice (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.04-6.13, p = 0.04). Only 80.4% of respondents tested all women for syphilis. There were regional differences in testing for some infections. The proportion of clinicians testing all women for HIV, HBV and syphilis was lower in Eastern Switzerland and the Zurich region (69.4% and 61.2%, respectively) than in other regions (range 77.1-88.1%, p <0.001). Most respondents (74.5%) said they would appreciate national guidelines about testing for infections during pregnancy. CONCLUSIONS: Testing practices for infections in pregnant women vary widely in Switzerland. More extensive national guidelines could improve consistency of testing practices. PMID- 27399958 TI - Rapidly Cycling Auras and Episodic Focal Dystonia in Anti-LGI1 Autoimmune Encephalitis. PMID- 27399959 TI - Evidence for Neurotoxicity Due to Morphine or Hydromorphone Use in Renal Impairment: A Systematic Review. AB - BACKGROUND: Opioids are the mainstay of pain control for patients with chronic pain. Often, opioids with reported active metabolites, such as morphine and hydromorphone, are thought to increase the risk of neurotoxicity in renal impairment. OBJECTIVES: To identify and assess the quality of evidence for neurotoxic effects in patients with renal impairment receiving morphine or hydromorphone. METHODS: Systematic searches were conducted of the following databases from inception to December 2015: MEDLINE, CINAHL, EMBASE, in addition to hand-searching relevant review articles' citations. Studies were included if they reported neurotoxic effects of either morphine or hydromorphone for chronic or malignant pain in patients with renal impairment. Review articles and case reports were excluded. Narrative review was undertaken. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess study quality. RESULTS: Six original articles, three prospective and three retrospective studies were identified and assessed. No relevant randomized clinical trials were identified. CONCLUSIONS: Although morphine and hydromorphone use may be associated with neurotoxic effects in patients with renal impairment, current evidence consists of very low-quality studies with conflicting findings. Clinicians may consider using either morphine or hydromorphone in mild-to moderate renal impairment, while closely monitoring for neurotoxic effects, particularly when used in high doses and for extended duration. PMID- 27399960 TI - Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice. AB - In the past two decades, titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in medicine, food industry and other daily life, while their possible interactions with the their influence and human body on human health remain not well understood. Thus, the study was designed to examine whether long term exposure to TiO2 NPs cause myocardial dysfunction which is involved in cardiac lesions and alter expression of genes and proteins involving inflammatory response in the mouse heart. The findings showed that intragastric feeding for nine consecutive months with TiO2 NPs resulted in titanium accumulation, infiltration of inflammatory cells and apoptosis of heart, reductions in net increases of body weight, cardiac indices of function (LV systolic pressure, maximal rate of pressure increase over time, maximal rate of pressure decrease over time and coronary flow), and increases in heart indices, cardiac indices of function (LV end-diastolic pressure and heart rate) in mice. TiO2 NPs also decreased ATP production in the hearts. Furthermore, TiO2 NPs increased expression of nuclear factor-kappaB, interleukin-lbeta and tumour necrosis factor alpha, and reduced expression of anti-inflammatory cytokines including suppressor of cytokine signaling (SOCS) 1 and SOCS3 in the cardiac tissue. These results suggest that TiO2 NPs may modulate the cardiac function and expression of inflammatory cytokines. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2917-2927, 2016. PMID- 27399961 TI - Estrogen receptor gene polymorphism in patients with degenerative lumbar scoliosis. AB - OBJECTIVE: To examine the association between development of degenerative lumbar scoliosis (DLS) and sex hormones. METHODS: We investigated the association between DLS and estrogen receptor alpha (ERalpha) gene polymorphisms in 184 patients with a diagnosis of DLS, by determining the presences of the Pvu II and Xba I polymorphisms, measuring bone mineral densities at the lumbar spine (LSBMD) and femoral neck (FNBMD), and by investigating biochemical markers of bone turnover and comparing these results with those of 220 healthy normal controls. RESULTS: Genotype frequencies in DLS patients and controls revealed a significant difference for the Pvu II polymorphism only (p = 0.0287). No significant difference was found between the DLS and control groups with respect to the Xba I polymorphism, bone mineral density (BMD), or biochemical markers. Furthermore, no significant association was observed between the Pvu II polymorphism and BMD, lumbar scoliosis, lateral listhesis, or biochemical markers in patients with DLS. CONCLUSION: These results suggest that the ERalpha Pvu II polymorphism influences the prevalence of DLS. PMID- 27399962 TI - It Is Time for Equal Pay for Equal Work for Physicians-Paging Dr Ledbetter. PMID- 27399963 TI - The Arabidopsis thaliana lectin receptor kinase LecRK-I.9 is required for full resistance to Pseudomonas syringae and affects jasmonate signalling. AB - On microbial attack, plants can detect invaders and activate plant innate immunity. For the detection of pathogen molecules or cell wall damage, plants employ receptors that trigger the activation of defence responses. Cell surface proteins that belong to large families of lectin receptor kinases are candidates to function as immune receptors. Here, the function of LecRK-I.9 (At5g60300), a legume-type lectin receptor kinase involved in cell wall-plasma membrane contacts and in extracellular ATP (eATP) perception, was studied through biochemical, gene expression and reverse genetics approaches. In Arabidopsis thaliana, LecRK-I.9 expression is rapidly, highly and locally induced on inoculation with avirulent strains of Pseudomonas syringae pv. tomato (Pst). Two allelic lecrk-I.9 knock-out mutants showed decreased resistance to Pst. Conversely, over-expression of LecRK I.9 led to increased resistance to Pst. The analysis of defence gene expression suggests an alteration of both the salicylic acid (SA) and jasmonic acid (JA) signalling pathways. In particular, LecRK-I.9 expression during plant-pathogen interaction was dependent on COI1 (CORONATINE INSENSITIVE 1) and JAR1 (JASMONATE RESISTANT 1) components, and JA-responsive transcription factors (TFs) showed altered levels of expression in plants over-expressing LecRK-I.9. A similar misregulation of these TFs was obtained by JA treatment. This study identified LecRK-I.9 as necessary for full resistance to Pst and demonstrated its involvement in the control of defence against pathogens through a regulation of JA signalling components. The role of LecRK-I.9 is discussed with regard to the potential molecular mechanisms linking JA signalling to cell wall damage and/or eATP perception. PMID- 27399964 TI - The Partitioning of Small Aromatic Molecules to Air-Water and Phospholipid Interfaces Mediated by Non-Hydrophobic Interactions. AB - Phenylalanine has an important role both in normal biological function and in disease states such as phenylketonuria (PKU) and amyloid fibril diseases. Two crucial aspects of phenylalanine behavior in biological systems are its preferential partitioning into membranes and its propensity to cluster. In order to examine the intermolecular interactions that give rise to this behavior, the surface partitioning behavior was investigated for a series of molecules structurally related to phenylalanine (phenylglycine, phenylacetic acid, and tyrosine) both experimentally and by molecular dynamics simulations. Surface tension measurements were performed over time for aromatic solutions both in the presence and in the absence of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayer films, which functioned as simple model membranes. The observed trends in surface activity defy simple predictions based on solubility and hydrophobicity. The possibility of clustering is investigated through a combination of Langmuir trough, nuclear magnetic resonance (NMR), fluorescence self-quenching, and mass spectroscopy measurements. It is concluded that clustering does not occur in solution to a significant extent for these molecules, but interfacial clustering is likely. An explanation for observed trends in surface activity is presented on the basis of cluster stability and molecular conformational flexibility. PMID- 27399965 TI - Pharyngeal constrictor muscle fatty change may contribute to obstructive sleep apnea-hypopnea syndrome: a prospective observational study. AB - CONCLUSIONS: Pharyngeal constrictor muscle injury and fatty changes may play important roles in the pathogenesis and progression of OSAHS. OBJECTIVE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a respiratory disorder caused by upper airway obstruction during sleep. The primary objectives of this study were to determine the ultrastructural characteristics of the pharyngeal constrictor muscle in patients with OSAHS. METHODS: A pharyngeal constrictor muscle specimen was collected from all subjects. The muscle cell ultrastructure was observed under electron microscopy. RESULTS: Eighteen male patients with OSAHS (OSAHS group) and 10 male body mass index-matched patients with chronic tonsillitis (control group) were enrolled in this study. All patients were obese adults. The apnea-hypopnea index (41.22 +/- 17.29 vs 2.30 +/- 1.10 events/h) was significantly higher and the lowest arterial oxygen saturation (76.00 +/- 8.57% vs 97.00 +/- 2.00%) was significantly lower in the OSAHS group than in the control group (both p < 0.001). Myofibril disorder, mitochondrial edema, and intramyocellular lipid droplets were observed in patients with OSAHS. There was a significant correlation between the number of lipid droplets and the apnea hypopnea index. PMID- 27399966 TI - Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non Europeans (including Asians) has a genetic basis. PMID- 27399968 TI - Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity. AB - Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development. PMID- 27399967 TI - Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits. AB - Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury. PMID- 27399970 TI - Random Sampling of Squamate Reptiles in Spanish Natural Reserves Reveals the Presence of Novel Adenoviruses in Lacertids (Family Lacertidae) and Worm Lizards (Amphisbaenia). AB - Here, we report the results of a large-scale PCR survey on the prevalence and diversity of adenoviruses (AdVs) in samples collected randomly from free-living reptiles. On the territories of the Guadarrama Mountains National Park in Central Spain and of the Chafarinas Islands in North Africa, cloacal swabs were taken from 318 specimens of eight native species representing five squamate reptilian families. The healthy-looking animals had been captured temporarily for physiological and ethological examinations, after which they were released. We found 22 AdV-positive samples in representatives of three species, all from Central Spain. Sequence analysis of the PCR products revealed the existence of three hitherto unknown AdVs in 11 Carpetane rock lizards (Iberolacerta cyreni), nine Iberian worm lizards (Blanus cinereus), and two Iberian green lizards (Lacerta schreiberi), respectively. Phylogeny inference showed every novel putative virus to be a member of the genus Atadenovirus. This is the very first description of the occurrence of AdVs in amphisbaenian and lacertid hosts. Unlike all squamate atadenoviruses examined previously, two of the novel putative AdVs had A+T rich DNA, a feature generally deemed to mirror previous host switch events. Our results shed new light on the diversity and evolution of atadenoviruses. PMID- 27399972 TI - Powering senescence: The ugly side of mitochondria. PMID- 27399969 TI - Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation. AB - The snub-nosed monkey genus Rhinopithecus includes five closely related species distributed across altitudinal gradients from 800 to 4,500 m. Rhinopithecus bieti, Rhinopithecus roxellana, and Rhinopithecus strykeri inhabit high-altitude habitats, whereas Rhinopithecus brelichi and Rhinopithecus avunculus inhabit lowland regions. We report the de novo whole-genome sequence of R. bieti and genomic sequences for the four other species. Eight shared substitutions were found in six genes related to lung function, DNA repair, and angiogenesis in the high-altitude snub-nosed monkeys. Functional assays showed that the high-altitude variant of CDT1 (Ala537Val) renders cells more resistant to UV irradiation, and the high-altitude variants of RNASE4 (Asn89Lys and Thr128Ile) confer enhanced ability to induce endothelial tube formation in vitro. Genomic scans in the R. bieti and R. roxellana populations identified signatures of selection between and within populations at genes involved in functions relevant to high-altitude adaptation. These results provide valuable insights into the adaptation to high altitude in the snub-nosed monkeys. PMID- 27399971 TI - ATP-consuming processes in hepatocytes of river lamprey Lampetra fluviatilis on the course of prespawning starvation. AB - The work was performed to establish which of the major ATP-consuming processes is the most important for surviving of hepatocytes of female lampreys on the course of prespawning starvation. The requirements of protein synthesis and Na(+)-K(+) ATPase for ATP in the cells were monitored by the changes in mitochondrial membrane potential (MMP) in the presence of corresponding inhibitors from the peak of metabolic depression (January-February) to the time of recovery from it (March-April) and spawning (May). Integrity of lamprey liver cells was estimated by catalytic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood plasma. In January-February, the share of ATP necessary for protein synthesis was 20-22%, whereas before spawning it decreased to 8-11%. Functioning of Na(+)-K(+)-pump required 22% of cellular ATP at the peak of metabolic depression, but 38% and 62% of ATP in March-April and May, respectively. Progression of prespawning period was accompanied by 3.75- and 1.6 fold rise of ALT and AST activities in blood plasma, respectively, whereas de Ritis coefficient decreased from 2.51+/-0.34 to 0.81+/-0.08, what indicates severe damage of hepatocyte membranes. Thus, the adaptive strategy of lamprey hepatocytes to develop metabolic depression under conditions of energy limitation is the selective production of proteins necessary for spawning, most probably vitellogenins. As spawning approaches, the maintenance of transmembrane ion gradients, membrane potential and cell volume to prevent premature cell death becomes the priority cell function. PMID- 27399973 TI - Quantitative Analysis of Collagen Produced by Rabbit Keratocytes using Second Harmonic Generation Microscopy. AB - PURPOSE: To quantitatively analyze the collagen produced by rabbit keratocytes treated with mitomycin C (MMC) and/or transforming growth factor-beta (TGF beta1), and to investigate the collagen arrangement in situ, using second harmonic generation (SHG) microscopy. METHODS: Keratocytes were divided into four groups: The keraotocytes in group rabbit keratocytes were treated with serum free medium containing 1% methylcellulose as controls. The cells in group TGF were received with TGF-beta1 (at 2 ng/ml) and the same medium as the control. After exposure to MMC at 0.02 mg/ml for 5 minutes, the cells in group MMC were received with the same treatment as controls. In group TGF-MMC, the cells were exposed to MMC at 0.02 mg/ml for 5 minutes first, and then treated as group TGF. The signals of collagen were detected by SHG at 2 and 4 weeks post-treatment. The collagen content, as well as the keratocyte numbers, was calculated by MetaMorph Offline. RESULTS: The collagen arrangement could be detected clearly by SHG. The cell number of group TGF was higher than other groups at 2 and 4 weeks post-treatment. The collagen content in group MMC was the least among all the groups at 2 weeks, while the collagen content in group TGF was higher than in group rabbit keratocytes and MMC at 4 weeks. No significant SHG side effects were found in cell proliferation and collagen deposition. CONCLUSIONS: SHG can provide a highly sensitive method to quantitatively measure collagen content, as well as to analyze its arrangement in situ. PMID- 27399974 TI - A polymorphism in human estrogen-related receptor beta (ESRRbeta) predicts audiometric temporary threshold shift. AB - OBJECTIVE: A non-synonymous single nucleotide polymorphism (rs61742642; C to T, P386S) in the ligand-binding domain of human estrogen-related receptor beta (ESRRbeta) showed possible association to noise-induced hearing loss (NIHL) in our previous study. DESIGN: This study was conducted to examine the effect of the ESRRbeta rs61742642 T variant on temporary threshold shift (TTS). TTS was induced by 10 minutes of exposure to audiometric narrow-band noise centered at 2000 Hz. Hearing thresholds and distortion product otoacoustic emissions input output function (DP IO) at 2000, 3000, and 4000 Hz were measured before and after the noise exposure. STUDY SAMPLE: Nineteen participants with rs61742642 CT genotype and 40 participants with rs61742642 CC genotype were recruited for the study. RESULTS: Participants with the CT genotype acquired a significantly greater TTS without convincing evidence of greater DP IO temporary level shift (DPTLS) compared to participants with the CC genotype. CONCLUSION: The results indicated that the ESRRbeta polymorphism is associated with TTS. Future studies were recommended to explore molecular pathways leading to increased susceptibility to NIHL. PMID- 27399975 TI - The path to personalized medicine in asthma. AB - INTRODUCTION: Asthma is a common respiratory disorder, since about 10% of the population suffer from this disease, and up to 10% have a severe form. Recent findings have allowed a greater and deeper understanding of the pathophysiological mechanisms, distinguishing two groups of patients according to the prevalent cellular population that drives the inflammatory process, and consequentially, to intervene on different cellular targets. AREAS COVERED: Currently, several biological drugs directly interfering with these pathophysiological mechanisms (namely IgE, IL-4, IL-5, IL-13, and IL-17) are under investigation. Expert commentary: With the elucidation of mechanisms, new targeted drugs have been developed. Asthma therapy is changing from a 'one size fits all' therapy to a 'precision medicine' model, where we may prescribe the most appropriate treatment for each patient. Moreover, in the near future, the possibility to act a 'sequential bio-combination therapy' can be envisaged, using different biological drugs in the same patient to act on different pathophysiological mechanisms. PMID- 27399976 TI - Patterns of abiotic niche shifts in allopolyploids relative to their progenitors. AB - Polyploidy has extensive genetic, physiological, morphological, and ecological ramifications. While the patterns underlying the genetic and morphological consequences of polyploidy are being rapidly elucidated, the effects on ecological niche are still largely unknown. This study investigated 13 allopolyploid systems in North America (10 ferns and three angiosperms) using digitized natural history museum specimens. The abiotic niches of the allopolyploids were compared with those of their diploid progenitors using ecological niche modeling, niche analyses, and multivariate analyses. We identified four patterns of niche shifts through our analyses: niche expansion, niche contraction, niche intermediacy, and niche novelty. The classification of these shifts depended on the amount of niche overlap and breadth between the polyploid and progenitors. The most common niche shift was niche intermediacy in which the polyploid inhabited a geographic range between that of the progenitors and had a high degree of niche overlap. Each polyploid had at least partial geographic sympatry and abiotic niche overlap with one of its progenitors, suggesting that biotic and/or microclimate factors may play a larger role in polyploid establishment than previously hypothesized. This study provides a baseline for future comparisons of the diverse outcomes of genome merger and duplication on abiotic niche preference. PMID- 27399977 TI - A new model of paired clinical teaching of international and Danish medical students. AB - INTRODUCTION: Since 2006, one hospital has offered two clinical courses in obstetrics/gynaecology and paediatrics to international (I) students. However, as I-student enrolment increased, the hospital faced cut-backs. As from 2010, I-team course evaluations therefore dropped to unacceptable levels and more I- than Danish (DK) students failed exams. Therefore, in 2012 we started a three-year internationalisation project (I-project) at two hospitals. The primary intervention was to pair training for I- and DK-students at clinical contact, and to offer an exclusive daily lecturer for I-teams. METHODS: We compared the course evaluations and exam grades of I-teams and DK-teams for two years prior to (107 from I-teams - 211 participants from DK-teams) and during the I-project (245 participants from I-teams - 575 from DK-teams). RESULTS: During the I-project, the I-teams' course evaluations increased to acceptable values and to levels comparable to the evaluation scores of DK-teams. Furthermore, I-students now considered that their communication with the patients was acceptable. Before the I-project, I-students had lower exam grades (median = 10 (range: 0-12)) than DK students (10 (4-12)) (p = 0.03), but during the I-project, exam grades increased to the levels achieved by DK-students (10 (2-12) - 10 (0-12) (p = 0.22), and no more I- than DK-students failed exams (p = 0.51). CONCLUSIONS: Pairing students for clinical training and allocating an exclusive lecturer for I-teams produced improved courses for internationalisation. Allocating an exclusive lecturer was associated with a cost of about 615 EUR per student per course when the team consisted of ten students. FUNDING: The Capital Region of Denmark and the University of Copenhagen. TRIAL REGISTRATION: not relevant. PMID- 27399978 TI - Lung cancer in younger patients. AB - INTRODUCTION: Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. METHODS: To assess the age differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients <= 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast track setting from January-December 2013, 312 newly diagnosed lung cancer patients were included. RESULTS: Patients <= 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours, a significantly higher proportion of the younger patients presented with advanced stage disease (p = 0.0392). Combined modality therapy was more common in younger patients (p = 0.0009), while chemotherapy appeared less prevalent among the elderly (p = 0.0015). CONCLUSIONS: Lung cancer in younger patients comprises a distinct clinicopathological entity with more frequent advanced stage disease and a significantly greater proportion with a family history of cancer. Implementing genetic background assessments and considering lung cancer as a possible diagnosis in younger, symptomatic patients, is of paramount importance. FUNDING: none. TRIAL REGISTRATION: The study was approved by the -Danish Data Protection Agency. PMID- 27399979 TI - Latent tuberculosis infection is prevalent among socially marginalised citizens in Aarhus, Denmark. AB - INTRODUCTION: Even in low-incidence countries, tuberculosis (TB) is common among socially marginalised people. Latent tuberculosis infection (LTBI) comprises a reservoir for future disease, and screening for LTBI and TB in these groups aids in the prevention and early detection of TB. METHODS: We performed a screening for LTBI with interferon gamma release assay (IGRA) testing, and TB screening with sputum smear examination at four shelters and four additional locations in a Danish urban area. Additionally, shelter volunteers were offered examination. RESULTS: A total of 145 subjects were tested; 124 with sputum smear and 100 with IGRA. Overall, 13 (13%) had LTBI, and one (0.8%) had smear-negative, culture positive, non-cavitating TB. Among 107 socially marginalised citizens, persons of Greenlandic origin had significantly more LTBI (40.0%) than Danish subjects (9.1%) (odds ratio (OR) = 6.67 (range: 1.55-28.63)), and other ethnicities had an intermediate prevalence of LTBI (18.2%) (OR versus Danish subjects = 2.22 (range: 0.35-14.06)). A total of 38 shelter volunteers were also included; IGRA was performed in 30 of those and one (3.33%) had LTBI. CONCLUSIONS: Our results confirm that a screening approach may reveal early cases of active TB. LTBI is common among the socially marginalised people, but varies substantially with ethnic origin. FUNDING: T-spot.TB kits were provided by Oxford Immunotec. TRIAL REGISTRATION: not relevant. PMID- 27399980 TI - Danish patients are positive towards fees for non-attendance in public hospitals. A qualitative study. AB - INTRODUCTION: Patients' non-attendance is a significant problem in modern healthcare. Non-attendance delays treatment, reduces efficiency and increases healthcare costs. For several years, the introduction of financial incentives such as a non-attendance fee has been discussed in Denmark. Set in the context of a tax-financed, free-for-all healthcare system, the political hesitance to introduce fees relates to concerns that additional fees may be badly received by tax-paying citizens and may undermine the political priority of patient equity. The aim of this qualitative sub-study was to investigate patients' attitudes towards a fee for non-attendance. METHODS: Six semi-structured focus group interviews were conducted with a total of 44 patients who had been informed about being charged a fee for non-attendance. Data were transcribed verbatim and analysed using a qualitative content analysis. RESULTS: Overall, patients' attitudes towards the non-attendance fee were positive. Non-attendance was viewed as evidence of disregard for the common free-for-all healthcare, and a fee was expected to motivate non-attendees to show up. However, most patients argued that certain groups (e.g. the mentally disabled) should be exempted from the fee. Furthermore, an implementation of fees should be easy to manage administratively and should not increase bureaucracy. CONCLUSION: In general, patients' attitudes towards implementing non-attendance fees are positive. FUNDING: Danish Regions, Ministry of Health and Central Denmark Region. TRIAL REGISTRATION: not relevant. PMID- 27399981 TI - Male circumcision does not result in inferior perceived male sexual function - a systematic review. AB - INTRODUCTION: The debate on non-medical male circumcision has gaining momentum during the past few years. The objective of this systematic review was to determine if circumcision, medical indication or age at circumcision had an impact on perceived sexual function in males. METHODS: Systematic searches were performed in MEDLINE and Embase. The included studies compared long-term sexual function in circumcised and non-circumcised males, before and after circumcision, or compared different ages at circumcision. The quality of the studies was assessed according to the level of evidence (Grade A-D). RESULTS: Database and hand searches yielded 3,677 records. Inclusion criteria were fulfilled in 38 studies including two randomised trials. Overall, the only identified differences in sexual function in circumcised males were decreased premature ejaculation and increased penile sensitivity (Grade A-B). Following non-medical circumcision, no inferior sexual function was reported (A-B). Following medical circumcision, most outcomes were comparable (B); however, problems in obtaining an orgasm were increased (C) and erectile dysfunction was reported with inconsistency (D). A younger age at circumcision seemed to cause less sexual dysfunction than circumcision later in life. CONCLUSIONS: The hypothesis of inferior male sexual function following circumcision could not be supported by the findings of this systematic review. However, further studies on medical circumcision and age at circumcision are required. PMID- 27399982 TI - Immunoglobulin for necrotising soft tissue infections (INSTINCT): protocol for a randomised trial. AB - INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may have beneficial effects. However, IVIG may also have adverse effects. With this trial we will estimate the effects of IVIG on a patient-reported outcome and other patient-centred outcomes in patients with NSTI. METHODS: INSTINCT is a randomised, double-blinded, parallel-group, placebo-controlled trial with concealed allocation of patients with NSTI 1:1 to IVIG or an equal volume of 0.9% saline. Patients are recruited at Rigshospitalet, Denmark. The primary outcome is the physical component summary score of the Medical Outcomes Study 36-Item Short Form Health Survey as assessed six months after randomisation. Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. CONCLUSION: This study will be the only completed trial testing IVIG for NSTI, thereby providing important data on a severely sick patient group. FUNDING: The trial is supported by CSL Behring in the form of trial medication and a ? 92,182 grant for trial conduct, research, nurse salary and statistical analyses. TRIAL REGISTRATION: The trial is registered with clinicaltrials.gov (NCT02111161). . PMID- 27399983 TI - National results after ventral hernia repair. AB - Ventral hernia repairs are among the most frequently performed surgical procedures. The variations of repair techniques are multiple and outcome has been unacceptable. Despite the high volume, it has been difficult to obtain sufficient data to provide evidence for best practice. In order to monitor national surgical quality and provide the warranted high volume data, the first national ventral hernia register (The Danish Ventral Hernia Database) was established in 2007 in Denmark. The present study series show that data from a well-established database supported by clinical examinations, patient files, questionnaires, and administrative data makes it possible to obtain nationwide high volume data and to achieve evidence for better outcome in a complex surgical condition as ventral hernia. Due to the high volume and included variables on surgical technique, it is now possible to make analyses adjusting for a variety of surgical techniques and different hernia specifications. We documented high 30-day complications and recurrence rates for both primary and secondary ventral hernias in a nationwide cohort. Furthermore, recurrence found by clinical examination was shown to exceed the number of patients undergoing reoperation for recurrence by a factor 4-5. The nationwide adjusted analyses proved that open mesh and laparoscopic repair for umbilical and epigastric hernias does not differ in 30-day outcome or in risk of recurrence. There is a minor risk reduction in early complications after open sutured repairs. However, the risk for a later recurrence repair is significantly higher after sutured repairs compared with mesh repairs. The study series showed that large hernia defects and open re-pairs were independent predictors for 30 day complications after an incisional hernia repair. Open procedures and large hernia defects were independent risk factors for a later recurrence re-pair. However, patients with large defects (> 15 cm) seemed to benefit from an open mesh repair compared with laparoscopic repairs. Additionally, the open sublay mesh position independently decreased the risk of recurrence repair compared with other open mesh positions. Emergency repair for a ventral hernia is dangerous and our studies revealed up to 15 times higher risk for post operative complications than after elective repairs. Especially females, older patients, and patients with small to medium sized hernias were at risk for an emergency repair compared with elective repairs. However, the many patients with untreated ventral hernias not included in the analysis, makes conclusions on risk factors for emergency repairs problematic. Because of the general lower morbidity and more advanced technology the proportion of laparoscopic procedures continues to increase at the expense of open surgery. The low incisional hernia rate is one of the major benefits of laparoscopic surgery. After 12 years follow-up, we demonstrated a low risk for a trocar site hernia repair, but the percentage of emergency repairs was relatively high. Parastomal hernias are relatively common. Nevertheless, few parastomal hernia repairs are performed annually. We documented that outcome in terms of early morbidity and recurrence is unacceptable. No difference in outcome is shown between open or laparoscopic repairs, or between the laparoscopic Keyhole and Sugerbaker technique. However, the 25% risk for 30-day mortality after an emergency parastomal hernia underlines the importance of special attention on these patients by centralisation to relative few dedicated centres and by more research to provide better surgical solutions. Based predominantly on nationwide data, the present thesis has accomplished pioneering results on outcome from ventral hernia repairs. The results have inspired to increased research and the development of other ventral hernia databases, as well as pointed out a number of risk factors for poor outcome and future challenges in ventral hernia surgery. DVHD and similar registers have a huge potential and can serve as an essential and important platform for further improvement of ventral hernia surgery in the future. PMID- 27399984 TI - Adherence to medical treatment in relation to pregnancy, birth outcome & breastfeeding behavior among women with Crohn's disease. AB - BACKGROUND: Crohn's disease (CD) is common among women of fertile age, and it often requires maintenance medical treatment. Adherence to medical treatment among women with CD prior to, during, and after pregnancy has, however, never been examined. Although CD women have increased risk of adverse pregnancy outcomes, little is known about predictors for these outcomes in women with CD. In addition, the impact of breastfeeding on disease activity remains controversial. AIMS: The aims of this PhD thesis were to determine adherence to treatment and to investigate predictors for and prevalence rates of non-adherence to maintenance medical treatment among women with CD prior to, during, and after pregnancy; to assess pregnancy outcomes among women with CD, taking medical treatment, smoking status, and disease activity into account; to assess breastfeeding rates and the impact of breastfeeding on the risk of relapse. METHODS: We conducted a population-based prevalence study including 154 women with CD who had given birth within a six-year period. We combined questionnaire data, data from medical records, and medical register data. RESULTS: Among 105 (80%) respondents, more than half reported taking medication with an overall high adherence rate of 69.8%. Counselling, previous pregnancy, and planned pregnancy seemed to decrease the likelihood of non-adherence, whereas smoking seemed to predict non-adherence prior to pregnancy, although our sample size prevented any firm conclusions. During pregnancy, the vast majority (95%) of CD women were in remission. The children's birth weight did not differ in relation to maternal medical treatment, but mean birth weight in children of smokers in medical treatment was 274 g lower than that of children of non-smokers in medical treatment. In our relatively small study CD women in medical treatment were not at increased risk of adverse pregnancy outcomes compared with untreated women with CD. In total, 87.6% of CD women were breastfeeding, and rates did not vary by medical treatment. Smoking and non-adherence seemed to predict relapse in CD during the postpartum period, whereas breastfeeding seemed protective against relapse. CONCLUSIONS: Although we generally had low statistical precision this thesis suggests that counselling regarding medical treatment may be an important factor for medical adherence among CD women of fertile age. In addition CD women in medical treatment did not seem at increased risk of adverse pregnancy outcome, but smoking predicted lower birth weight. Breastfeeding did not seem to increase the risk of relapse in CD. PMID- 27399985 TI - Substrate kinetics in patients with disorders of skeletal muscle metabolism. AB - The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before exercise, exercise capacity is worsened, most likely due to the sympatho-adrenergt response, that increases heart rate and blocks gluconeogenesis. Substrate turnover studies in patients with McArdle disease and phosphorylase b kinase deficiency showed that palmitate lipolysis, utilization and plasma concentration was higher and total CHO lower in the patients during exercise vs. healthy subjects. In patients with low muscle mass glucose homeostasis is impaired, and our findings showed that these patients are prone to develop hypoglycaemia during prolonged fasting. The following studies emphasize the importance of skeletal muscle in production of energy, both when skeletal muscle lack important metabolic enzymes (metabolic myopathies), and when skeletal muscle mass is low. PMID- 27399986 TI - Robotic-assisted laparoscopic hysterectomy for women with endometrial cancer - complications, women's experiences, quality of life and a health economic evaluation. AB - This thesis contains four studies all focusing on women with endometrial cancer undergoing robotic-assisted laparoscopic hysterectomy (RALH). Women with endometrial cancer are typically elderly with co-morbidities. RALH is a relatively new treatment option which has been introduced and adopted over the last decade without randomised controlled trials (RCTs) to prove superiority over other surgical alternatives. The purpose of the thesis was to explore and describe patient and health economic outcomes of RALH for women with endometrial cancer using different research approaches. The first study was a retrospective descriptive cohort study with 235 women. The aim was to explore types and incidence of post-operative complications within 12 months after RALH reported with the Clavien-Dindo scale. We found that 6% had severe complications and that women with lymphadenectomy did not have an increased rate of complications. Urinary tract and port site infections were the most frequent complications. The second study was a qualitative interview study where we explored the experience of undergoing RALH. Using content analysis, we analysed semi-structured interviews with 12 women who had undergone RALH on average 12 weeks earlier. The women were positive towards the robotic approach and felt recovered shortly after. They expressed uncertainty with the normal course of bleeding and bowel movement post-operatively as well as with the new anatomy. The third study was an economic evaluation; an activity-based costing study including 360 women comparing total abdominal hysterectomy (TAH) to RALH. This study showed that for women with endometrial cancer, RALH was cheaper compared to TAH, mainly due to fewer complications and shorter length of stay (LOS) that counterbalanced the higher robotic expenses. When including all cost drivers the analysis showed that the RALH procedure was more than 9.000 Danish kroner (DKK) cheaper than the TAH. Increased age and Type 2 diabetes appeared to increase costs. The fourth study was a prospective cohort study of 139 women who were followed four months after surgery with the aim to assess short term changes in health-related quality of life (HRQoL), symptoms and function after RALH. Both a general and an illness specific HRQoL questionnaire were used. The preoperative baseline measurement was compared with measurements at one and five weeks and four months post operatively. The women also selfreported their level of activity once a week for the first five weeks after surgery. We found that HRQoL was back to baseline level at five weeks post-operatively for the majority of women. Fatigue, constipation, gastrointestinal symptoms, pain, appetite and change of taste were negatively affected short-term. At five weeks the mean level of physical activity resumed was 84%. Together, the studies indicate that RALH is a well-tolerated surgical treatment for women with endometrial cancer, and post-operative complications appear fewer and less severe compared to previous open surgery. This points towards RALH being clinically and economically efficient. The women experienced that RALH was easy to overcome and they felt recovered shortly after. However, they expressed uncertainty about the normal post-operative cause and reported changes in functions and symptoms short term after surgery. These changes should be addressed in the preoperative information and at the post operative follow-up. It is difficult imagining a RCT of robotic-assisted laparoscopic hysterectomy being conducted in the future due to reluctance towards randomisation to open surgery. However, it would be advisable continuously to monitor relevant surgical and patient-reported outcomes as indications for robotic surgery may alter, experiences may develop and further technical advances may change robotic surgery for women with endometrial cancer in the future. PMID- 27399987 TI - Systemic and local collagen turnover in hernia patients. AB - BACKGROUND: Hernia formation is a multifactorial disease involving important endogenous factors possibly affected by exogenous factors. Alterations in collagen composition seem to contribute to abdominal wall hernia formation, possibly related to increased collagen breakdown. The collagen composition appears altered in fascial tissue but also in skin biopsies, suggesting that the collagen alterations are systemic. More pronounced collagen alterations are found in patients with hernia recurrences. Hypothetically, primary inguinal hernias are formed due to a systemic predisposition to altered connective tissue, whereas impaired healing influences on the development of incisional hernias and hernia recurrences. The overall objective of this thesis was to investigate the collagen turnover systemically and locally in patients with primary inguinal hernia, multiple hernias and incisional hernia. METHODS AND RESULTS: In a systematic literature review, a total of 55 original articles were reviewed evaluating connective tissue alterations in patients with abdominal wall hernias. Patients with inguinal and incisional hernias exhibit a decreased type I to III collagen ratio in fascia and skin biopsies with the most pronounced alterations found in patients with direct inguinal hernia and hernia recurrence. An increased level of MMP-2 was reported in patients with inguinal hernias. In a nationwide study from the Danish Hernia Database, 92,283 patients with an inguinal hernia repair were identified from January 1998 until June 2010. A total of 843 patients were also registered with a ventral hernia repair. Direct (OR = 1.28 [95% C.I. 1.08-1.51]) and recurrent (OR = 1.76 [95% C.I. 1.39-2.23]) inguinal hernia repairs were significantly associated with ventral hernia repair compared to indirect inguinal hernia repair after adjustment for gender, age and surgical approach. In a multivariable subgroup analysis, direct and recurrent inguinal hernia repair were associated with primary ventral hernia surgery, whereas only recurrent inguinal hernia repair was associated with secondary ventral hernia surgery. In a cohort of 305 patients followed up a median of 3.7 years after emergency or elective laparotomy, a total of 79 patients were identified with an incisional hernia. Patients were subgrouped based on the identified risk factors male gender and smoking in eight groups with nine patients in each. Pooled serum samples were screened for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, TIMP-1, TIMP-2, and TIMP-4 with a multiarray and zymography. The screening indicated differences in MMP-9 and TIMP-1, which were measured in serum samples of the whole patient cohort with ELISA. There were no differences in systemic MMP 9 and TIMP-1 levels between patients with and without incisional hernia. Patients were enrolled consecutively in four groups: 1) patients undergoing elective laparoscopic cholecystectomy without hernias (N = 18), patients operated on for 2) primary unilateral inguinal hernia (N = 17), 3) multiple hernias defined as three or more primary hernias (N = 21) and 4) incisional hernia (N = 25). Venous blood was collected preoperatively. Pro-MMP-2 and pro-MMP-9 were measured in serum by gelatine zymography, and there were no significant differences between hernia patients and controls. Furthermore, serological biomarkers for type I, III, IV and V collagen turnover were measured in serum by solid-phase competitive immunoassays. In patients with inguinal hernia, type III and V collagen turnover were significantly decreased, whereas type IV collagen turnover was significantly increased. In incisional hernia patients, type V collagen turnover was significantly decreased, whereas type IV collagen turnover was significantly increased. Type IV collagen turnover seem to predict the presence of both inguinal and incisional hernia. An ePTFE tube was implanted perioperatively in all four patient groups and explanted on the tenth post-operative day. Newly synthesized granulation tissue in the ePFTE tube represents the patients' wound healing potential. Hydroxyproline levels were measured as a marker for total collagen deposition and were unaltered in hernia patients compared to controls. Pro-MMP-2 and pro-MMP-9 levels in the PTFE tubes did not differ between hernia patients and controls. A fascia transversalis biopsy was excised perioperatively in all four patient groups. There were no significant differences between hernia patients and controls in total collagen concentration or morphology of the fascia transversalis. ? CONCLUSIONS: Direct and recurrent inguinal hernia repair are associated with ventral hernia repair, suggesting a systemic predisposition to the hernia disease. MMPs are not suitable as serum biomarkers for inguinal or incisional hernia disease. Serum biomarkers for collagen turnover are altered in both inguinal and incisional hernia patients; specifically markers for type IV collagen turnover seem to predict the presence of hernias. A systemic biomarker predicting hernia disease would be useful to plan a tailored surgical strategy for the individual patient. PMID- 27399989 TI - The mediating role of spirituality on professional values and self-efficacy: a study of senior nursing students. AB - AIM: The aim of this study was to identify the significance of spirituality in enhancing self-efficacy related to professional values in senior nursing students. BACKGROUND: Self-efficacy can predict job satisfaction and performance as professional nurses in clinical settings. Senior nursing students should have the level of self-efficacy that enables them to perform professional roles based on professional values, because they will enter clinical settings immediately after graduation. Spirituality may help senior nursing students during the transition to professional life to reflect on their skills, knowledge and situations to enhance self-efficacy based on professional values. DESIGN: An exploratory, cross-sectional design was used in this study. METHODS: A total of 194 senior nursing students in South Korea were recruited in 2014. They completed self-reported questionnaires consisting of demographic questions, Spiritual Assessment Scale, Self-Efficacy Scale and Nursing Professional Values inventory. A Sobel test was done to determine the mediating effect of spirituality on the relationship between nursing professional values and self-efficacy. RESULTS: The findings showed a positive correlation between professional values, spirituality and self-efficacy in nursing students. According to the Sobel test, spirituality had a mediating effect on the relationship between professional values and self efficacy in senior nursing students. CONCLUSION: Spirituality can be a foundation that provides senior nursing students with higher self-efficacy so that they are able to perform their professional roles based on their professional values. The findings can guide nursing educators to include spiritual development of nursing students to enhance the self-efficacy of senior nursing students, the future of the nursing profession. PMID- 27399988 TI - Folding of Protein Ions in the Gas Phase after Cation-to-Anion Proton-Transfer Reactions. AB - The structure and folding of a protein in solution depends on noncovalent interactions within the protein and those with surrounding ions and molecules. Decoupling these interactions in solution is challenging, which has hindered the development of accurate physics-based models for structure prediction. Investigations of proteins in the gas phase can be used to selectively decouple factors affecting the structures of proteins. Here, we use cation-to-anion proton transfer reactions (CAPTR) to reduce the charge states of denatured ubiquitin ions in the gas phase, and ion mobility to probe their structures. In CAPTR, a precursor charge state is selected (P) and reacted with monoanions to generate charge-reduced product ions (C). Following each CAPTR event, denatured ubiquitin ions (13+ to 6+) yield products that rapidly isomerize to structures that have smaller collision cross sections (Omega). The Omega values of CAPTR product ions depend strongly on C and very weakly on P. Pre- and post-CAPTR activation was then used to probe the potential-energy surfaces of the precursor and product ions, respectively. Post-CAPTR activation showed that ions of different P fold differently and populate different regions of the potential-energy surface of that ion. Finally, pre-CAPTR activation showed that the structures of protein ions can be indirectly investigated using ion mobility of their CAPTR product ions, even for subtle structural differences that are not apparent from ion mobility characterization of the activated precursor ions. More generally, these results show that CAPTR strongly complements existing techniques for characterizing the structures and dynamics of biological molecules in the gas phase. PMID- 27399990 TI - The Affordable Care Act and the Future of US Health Care. PMID- 27399991 TI - Surgical Management of the Constricted or Obliterated Vagina. AB - Management of the constricted or obliterated vagina demands an understanding and recognition of the potential etiologies leading to this presentation. A thorough and comprehensive medical and surgical review is required to arrive at an accurate diagnosis, which then will guide medical or surgical intervention. It is paramount to recognize when underlying medical conditions are contributing to these conditions and to begin medical therapy; failure to do so will often yield suboptimal results. When these conditions arise after surgical interventions, compensatory surgical techniques that correct upper and lower vaginal strictures or obliteration include incision through the stricture, vaginal advancement, Z plasty, skin grafts, perineal flaps, and abdominal flaps and grafts. Postoperative surveillance and dilation are critical to optimize long-term success. PMID- 27399992 TI - Fertility Treatments in the United States: Improving Access and Outcomes. AB - The recently released National Public Health Action Plan for the Detection, Prevention, and Management of Infertility calls for better access to high-quality infertility services and improved safety of fertility treatments. Both assisted reproductive technology (ART) and non-ART fertility treatments have allowed millions of patients worldwide to overcome infertility-a disease of the reproductive system and important public health issue. However, there are substantial disparities in access to effective treatments in the United States, largely attributable to high out-of-pocket costs, especially for ART. Moreover, the outcomes of fertility treatments are often complicated by the large proportion of multiple births with substantial health risks for both neonates and mothers. Prevention of multiple births is difficult during non-ART fertility treatments but can be effective with single-embryo transfer during ART. Several U.S. states have enacted legislative mandates that require private insurers to cover some portion of the costs associated with fertility treatments and thus reduce the financial pressure to transfer multiple embryos during ART. Although studies have shown that insurance coverage reduces per-cycle multiple births to a certain degree, states with insurance mandates have more ART-related multiple births attributable to substantially larger number of ART-conceived neonates. Experience from other countries shows that access to ART can be improved without concomitant increases in multiple births by providing reimbursement for ART in combination with restrictions on the number of embryos transferred per cycle. Such approaches may or may not be successful in the United States with its unique and complex health care system. PMID- 27399993 TI - Long-Term Mortality After Hypertensive Disease of Pregnancy. PMID- 27399994 TI - Connect the Dots-August 2016. PMID- 27399995 TI - Sacral Neuromodulation for the Treatment of Persistent Genital Arousal Disorder. AB - BACKGROUND: Patients affected with persistent genital arousal disorder report unprovoked, excessive, and unremitting genital arousal unrelated to sexual desire. Those afflicted experience severe physical and psychological distress with significant feelings of shame, guilt, and frustration. Definitive treatment options for this disorder are limited. CASE: We present the case of a 32-year-old woman, gravida 1 para 1, with persistent genital arousal disorder after treatment of an uncomplicated urinary tract infection while in a military-deployed environment. After numerous treatment modalities failed, she responded to an implanted sacral neuromodulator. CONCLUSION: Persistent genital arousal disorder may be the result of upregulated sacral nerve pathways. We report the use of sacral neuromodulation using unique program settings, which may be an effective alternative in the treatment of this distressing disorder. PMID- 27399996 TI - Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio and Time to Delivery in Women With Suspected Preeclampsia. AB - OBJECTIVE: To assess the association of a serum soluble fms-like tyrosine kinase 1-to-placental growth factor (sFlt-1-to-PlGF) ratio of greater than 38 with time to delivery and preterm birth. METHODS: Secondary analysis of an observational cohort study that included women 18 years of age or older from 24 to 36 6/7 weeks of gestation at their first study visit with suspected (not confirmed) preeclampsia. Participants were recruited from December 2010 to January 2014 at 30 sites in 14 countries. A total of 1,041 women were included in time-to delivery analysis and 848 in preterm birth analysis. RESULTS: Women with an sFlt 1-to-PlGF ratio greater than 38 (n=250) had a 2.9-fold greater likelihood of imminent delivery (ie, delivery on the day of the test) (Cox regression hazard ratio 2.9; P<.001) and shorter remaining time to delivery (median 17 [interquartile range 10-26] compared with 51 [interquartile range 30-75] days, respectively; Weibull regression factor 0.62; P<.001) than women with an sFlt-1 to-PlGF ratio of 38 or less, whether or not they developed preeclampsia. For women who did not (n=842) and did develop preeclampsia (n=199), significant correlations were seen between an sFlt-1-to-PlGF ratio greater than 38 and preterm birth (r=0.44 and r=0.46; both P<.001). Among women who did not develop preeclampsia, those who underwent iatrogenic preterm delivery had higher median sFlt-1-to-PlGF ratios at their first visit (35.3, interquartile range 6.8-104.0) than those who did not (8.4, interquartile range 3.4-30.6) or who delivered at term (4.3, interquartile range 2.4-10.9). CONCLUSIONS: In women undergoing evaluation for suspected preeclampsia, a serum sFlt-1-to-PlGF ratio greater than 38 is associated with a shorter remaining pregnancy duration and a higher risk of preterm delivery. PMID- 27399997 TI - Histologic Chorioamnionitis and Funisitis After Laser Surgery for Twin-Twin Transfusion Syndrome. AB - OBJECTIVE: To estimate the incidence of histologic chorioamnionitis and funisitis after fetoscopic laser surgery for the management of twin-twin transfusion syndrome. METHODS: A case-control study was performed at the Leiden University Medical Center from 2013 to 2014. All patients with twin-twin transfusion syndrome managed with laser surgery during the study period were included and compared with a control group of all monochorionic twins not treated with laser surgery. We excluded patients with fetal demise or higher order pregnancies. Placentas were reviewed for the presence and degree of chorioamnionitis and presence or absence of fetal inflammatory response. The primary outcome was the incidence of histologic chorioamnionitis and funisitis after laser surgery. Odds ratios (ORs) and 95% confidence intervals (CIs) for primary outcomes were calculated. A P value of <.05 was considered as statistical significance. RESULTS: Sixty-two patients treated with laser surgery were included in the study group and compared with 64 patients in the control group. The incidence of histologic chorioamnionitis was 13% (8/62) in the laser group compared with 5% (3/64) in the control group (OR 3.0, 95% CI 0.8-11.9, P=.12). Funisitis occurred in 8% (10/124) in the laser group compared with 0% in the control group (OR 11.1, 95% CI 1.3-96.9, P=.03). Histologic chorioamnionitis with or without funisitis after laser surgery was associated with a shorter laser-to-delivery interval (median 6.6 [range 3.4-14.1] compared with 13.6 [4.4-20.1] weeks, P<.01) and lower gestational age at birth (median 28.1 [range 23.1-32.6] compared with 32.7 [24.4-37.0] weeks, P<.01). CONCLUSION: These findings suggest that laser surgery for twin-twin transfusion syndrome is associated with an increased risk of funisitis. PMID- 27399998 TI - Phenazopyridine for Evaluation of Ureteral Patency: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the usefulness of phenazopyridine for confirmation of ureteral patency during intraoperative cystoscopy. METHODS: We conducted a randomized controlled trial comparing use of phenazopyridine with no medications for evaluation of ureteral patency during intraoperative cystoscopy in women undergoing pelvic surgery. The primary study outcome was time to visualize ureteral urine efflux. To detect a 3-minute difference with alpha of 0.05 using a two-sided, two-sample t test and beta 0.80 required 98 patients equally divided into two groups. RESULTS: A total of 104 women were randomized from April to December 2015. Patients in the treatment group tended to be older (P=.02); otherwise, study groups were similar. Time to visualize ureteral urine efflux did not differ between study groups with a mean time of 2 minutes 40 seconds (+/-2 minutes 38 seconds) in the control group and 2 minutes 53 seconds (+/-4 minutes 35 seconds) in the treatment group (P=.77). Regarding the surgeon survey, surgeons felt less frustrated and impatient in visualization of ureteral urine efflux in the treatment group compared with the control group (mean response 1.5+/-0.8 in treatment compared with 2.0+/-1.0 in control, P=.007), and surgeons felt that the cystoscopy took too long more often in the control than in the treatment group (1.7+/-0.9 in treatment compared with 2.1+/-1.0 in control, P=.02). Trial of void result differed significantly between groups with fewer patients in the treatment group failing a void trial (P=.04). There were no adverse events related to phenazopyridine use. CONCLUSION: Preoperative phenazopyridine is a useful and cost-saving medication for use in planned cystoscopy for evaluation of ureteral patency. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02424149. PMID- 27399999 TI - Experience With Opportunistic Salpingectomy in a Large, Community-Based Health System in the United States. AB - OBJECTIVE: To evaluate the trend in uptake of salpingectomy at the time of hysterectomy and assess physicians' attitudes toward the practice. METHODS: This was a retrospective cohort study using the electronic medical record to identify women 18 years of age or older undergoing hysterectomy from June 2011 to May 2014 in a large integrated health care delivery system. The primary outcome was the change in rate of opportunistic salpingectomy over time and after a systemwide practice recommendation was issued in May 2013. Secondary outcomes included data on blood loss, operating time, and length of stay. RESULTS: Of the 12,143 hysterectomies performed over the 3-year study period, 7,498 were performed without oophorectomy. There was a statistically significant rise in rate of salpingectomy over time from 14.7% for June 2011 to May 2012 to 44.6% from June 2012 to May 2013 and to 72.7% from June 2013 to May 2014 (P<.001). Sixty-one percent of laparoscopic hysterectomies were performed with salpingectomy, whereas only 25% of abdominal and 17% of vaginal hysterectomies had salpingectomies. Median estimated blood loss was lower in the salpingectomy group, 100 compared with 150 mL (P<.01). There was a significantly shorter median operating time (147 compared with 154 minutes, P=.002) for laparoscopic hysterectomy with bilateral salpingectomy compared with laparoscopic hysterectomy alone. CONCLUSION: Rates of salpingectomy increased significantly over time, consistent with the high reported acceptance rate reported by health care providers and highlighting the importance of physician education to improve compliance with risk-reducing clinical strategies. PMID- 27400000 TI - Recurrence of Preterm Birth and Early Term Birth. AB - OBJECTIVE: To examine recurrent preterm birth and early term birth in women's initial and immediately subsequent pregnancies. METHODS: This retrospective cohort study included 163,889 women who delivered their first and second liveborn singleton neonates between 20 and 44 weeks of gestation in California from 2005 through 2011. Data from hospital discharge records and birth certificates were used for analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for risk factors. RESULTS: Shorter gestational duration in the first pregnancy increased the risk of subsequent preterm birth (both early, before 32 weeks of gestation, and later, from 32 to 36 weeks of gestation) as well as early term birth (37-38 weeks of gestation). Compared with women with a prior term birth, women with a prior early preterm birth (before 32 weeks of gestation) were at the highest risk for a subsequent early preterm birth (58/935 [6.2%] compared with 367/118,505 [0.3%], adjusted OR 23.3, 95% CI 17.2-31.7). Women with a prior early term birth had more than a twofold increased risk for subsequent preterm birth (before 32 weeks of gestation: 171/36,017 [0.5%], adjusted OR 2.0, 95% CI 1.6-2.3; from 32 to 36 weeks of gestation: 2,086/36,017 [6.8%], adjusted OR 3.0, 95% CI 2.9-3.2) or early term birth (13,582/36,017 [37.7%], adjusted OR 2.2, 95% CI 2.2-2.3). CONCLUSION: Both preterm birth and early term birth are associated with these outcomes in a subsequent pregnancy. Increased clinical attention and research efforts may benefit from a focus on women with a prior early term birth as well as those with prior preterm birth. PMID- 27400001 TI - Diagnostic Biomarkers in Women With Suspected Preeclampsia in a Prospective Multicenter Study. AB - OBJECTIVE: To evaluate 47 biomarkers (selected from the current medical literature), in isolation or in combination with placental growth factor (PlGF), to determine the need for delivery within 14 days, in women presenting with suspected preterm preeclampsia. METHODS: In a prospective, multicenter observational study, 47 biomarkers were measured in 423 women presenting with suspected preterm preeclampsia (in two prespecified groups: group 1 at less than 35 weeks of gestation and group 2 presenting between 35 0/7 and 36 6/7 weeks of gestation) to evaluate their ability to determine the primary endpoint: preeclampsia requiring delivery within 14 days. Using factor analysis and stepwise logistic regression, we sought one or more additional biomarkers for optimal determination of the primary endpoint. RESULTS: In women presenting at less than 35 weeks of gestation (n=286), the best performing combination of PlGF, podocalyxin, endoglin, procalcitonin (receiver operating curve [ROC] area 0.90, 95% confidence interval [CI] 0.86-0.93) was not statistically better than PlGF alone (ROC 0.87, 95% CI 0.83-0.92; P=.43) for preeclampsia requiring delivery within 14 days. Two other single markers had test performance that was not significantly different to PlGF (soluble fms-like tyrosine kinase-1 [sFlt-1] ROC 0.83, 95% CI 0.78-0.88; endoglin ROC 0.83, 95% CI 0.79-0.88). Similar findings were found in women presenting between 35 0/7 and 36 6/7 weeks of gestation (n=137): ROC for PlGF alone 0.75 (95% CI 0.67-0.83); ROC for PlGF, cystatin, pregnancy-associated plasma protein A in combination 0.81 (95% CI 0.74-0.88; P=.40). CONCLUSION: This study supports the growing body of evidence that a single angiogenesis-related biomarker (PlGF, sFlt-1, or endoglin) alone represents a useful diagnostic test for women presenting with suspected preterm preeclampsia. PMID- 27400003 TI - A Sanitary Pad for Self-Assessment of Rupture of Membranes. AB - BACKGROUND: Multistep immunoassay kits for the diagnosis of rupture of membranes are relatively complex and are not designed to be used by pregnant women themselves. These kits require procedural steps of specimen extraction and preparation. We evaluated the ability of a sanitary pad containing a qualitative immunoassay for alpha-fetoprotein (AFP) to serve as a one-step self-test to detect amniotic fluid leakage. TECHNIQUE: Four sets of pads were evaluated. The pads in the study set were worn by 288 pregnant women with confirmed rupture of membranes. Three controls were evaluated: 1) pads worn by 93 pregnant women with intact membranes, 2) additional pads instilled with urine specimens obtained from the 381 women described previously (study set plus control set 1), and 3) pads instilled with semen collected from 40 men. EXPERIENCE: All 288 pads that absorbed amniotic fluid had positive results. Approximately half of the pads absorbed with normal vaginal discharge had a sufficient amount to yield valid results, which were all negative. All 381 pads with instilled urine and all 40 pads with instilled semen had negative results. CONCLUSION: An immunoassay for AFP, embedded in a pad, appears to be a feasible and reproducible self-test for the detection of rupture of membranes. PMID- 27400002 TI - Early Compared With Delayed Physician Rounds on Patient Satisfaction of Postpartum Women: A Randomized Controlled Trial. AB - OBJECTIVE: To investigate whether delayed timing of physician rounds improves patient satisfaction for postpartum women. METHODS: Women were randomized to early (5-7 AM) or delayed (8-10 AM) physician rounding. Women with stillbirth, high-risk pregnancy, or complications precluding delayed rounding were excluded. At discharge, women completed a modified Hospital Consumer Assessment of Healthcare Providers and Systems survey. The primary outcome was rating of the hospital. Secondary outcomes included patient assessment of patient-physician communication, various hospital experiences, and timing of maternal and neonatal discharge. We estimated that 74 women were needed to detect a 20% difference in rating of the hospital (0-10 score) between groups (assumption P=.05, power 90%). Given limited information on primary outcome, an a priori plan was in place to conduct the study for 2 months. RESULTS: One hundred fifty-two women were randomized (n=76 early rounding; n=76 delayed rounding). More women had a cesarean delivery in the early compared with the delayed rounding group (47.4% compared with 22.4%). Median rating of the hospital was higher in the delayed as compared with the early rounding group (9.0 [7.0-9.0] compared with 7.0 [6.0 8.0]; P<.01). Median scores regarding physician communication and perception of hospital experiences were higher in the delayed compared with the early group (8.0 [7.0-9.0] compared with 6.0 [5.0-7.0]; P<.001). Adjustment for delivery mode did not alter results (P<.01). No differences in timing of maternal (P=.47) or neonatal hospital discharge (P=.35) were observed. CONCLUSION: Postpartum women receiving delayed physician rounding were more satisfied with their hospital experience and patient-physician communication without prolonging maternal or neonatal discharge. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02432573. PMID- 27400004 TI - Cryopreserved Human Umbilical Cord for In Utero Myeloschisis Repair. AB - BACKGROUND: There is an urgent need is for a regenerative patch for in utero repair of spina bifida in situations in which primary closure is difficult. CASES: We present two cases of large myeloschisis defects that underwent in utero spina bifida repair at midgestation with closure of the skin defect by using a cryopreserved human umbilical cord patch. The pregnancies were uncomplicated, and the births occurred at 37 weeks by planned cesarean delivery. The repair sites were intact with no evidence of cerebrospinal fluid leakage, with skin regenerated after delivery over a period of 3-4 weeks. The short-term outcomes after delivery showed reversal of hindbrain herniation, minimal spinal cord tethering, and normal function of the lower extremities. CONCLUSION: Cryopreserved human umbilical cord may be a suitable patch system for the spina bifida closure. PMID- 27400005 TI - Perinatal and Hemodynamic Evaluation of Sildenafil Citrate for Preeclampsia Treatment: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate whether therapy with sildenafil citrate prolongs gestation in women with preeclampsia. METHODS: In a randomized double-blind, placebo controlled trial, 100 singleton pregnancies with preeclampsia between 24 and 33 weeks of gestation were randomized to 50 mg oral sildenafil citrate every 8 hours or placebo. The primary outcome was prolongation of pregnancy from randomization to delivery. Secondary outcomes were changes in resistance indices of uterine, umbilical, and middle cerebral arteries by Doppler, fetal and maternal complications, and adverse neonatal outcomes. Power analysis estimated that to detect a difference of 5 days in pregnancy duration, 43 patients would have to be randomized to each group. RESULTS: From June 2013 to October 2015, 50 patients were randomized to each group. Pregnancy duration was on average 4 days longer (14.4 days, 95% confidence interval [CI] 12.5-16.6 days compared with 10.4 days, 95% CI 8.4-12.3 days, P=.008) and percent reduction in pulsatility indices of uterine and umbilical arteries higher (22.5% and 18.5%, compared with placebo 2.1% and 2.5%, P<.001) for patients treated with sildenafil compared with placebo. Maternal blood pressure before and 24 hours after randomization was lower with sildenafil (sildenafil: 100.3+/-5.6 mm Hg compared with 116.4+/-5.1 mm Hg, P<.05; placebo: 110.6+/-6.2 mm Hg compared with 114.7+/-6.5 mm Hg, P=.21). There was no difference in perinatal morbidity, mortality, or adverse effects between groups. CONCLUSION: Therapy with sildenafil citrate was associated with pregnancy prolongation of approximately 4 days compared with placebo in women with preeclampsia. CLINICAL TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, www.ensaiosclinicos.gov.br, RBR-8qj4p5. PMID- 27400006 TI - All-Cause and Cause-Specific Mortality After Hypertensive Disease of Pregnancy. AB - OBJECTIVE: To assess whether women with a history of hypertensive disease of pregnancy have increased risk for early adult mortality. METHODS: In this retrospective cohort study, women with one or more singleton pregnancies (1939 2012) with birth certificate information in the Utah Population Database were included. Diagnoses were categorized into gestational hypertension; preeclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; and eclampsia. Women with more than one pregnancy with hypertensive disease (exposed) were included only once, assigned to the most severe category. Exposed women were matched one to two to unexposed women by age, year of childbirth, and parity at the time of the index pregnancy. The causes of death were ascertained using Utah death certificates and the fact of death was supplemented with the Social Security Death Index. Hazard ratios for cause-specific mortality among exposed women compared with unexposed women were estimated using Cox regressions adjusting for neonatal sex, parental education, preterm delivery, race-ethnicity, and maternal marital status. RESULTS: A total of 60,580 exposed women were matched to 123,140 unexposed women; 4,520 (7.46%) exposed and 6,776 (5.50%) unexposed women had died by 2012. All-cause mortality was significantly higher among women with hypertensive disease of pregnancy (adjusted hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.57-1.73). Exposed women's greatest excess mortality risks were from Alzheimer disease (adjusted HR 3.44, 95% CI 1.00 11.82), diabetes (adjusted HR 2.80, 95% CI 2.20-3.55), ischemic heart disease (adjusted HR 2.23, 95% CI 1.90-2.63), and stroke (adjusted HR 1.88, 95% CI 1.53 2.32). CONCLUSION: Women with hypertensive disease of pregnancy have increased mortality risk, particularly for Alzheimer disease, diabetes, ischemic heart disease, and stroke. PMID- 27400007 TI - Salpingo-Oophorectomy by Transvaginal Natural Orifice Transluminal Endoscopic Surgery. AB - BACKGROUND: Vaginal hysterectomy is the preferred route of hysterectomy in benign gynecologic disease; however, a vaginal salpingo-oophorectomy can sometimes be technically challenging. Even the most skilled vaginal surgeon will occasionally have to convert to an abdominal approach to complete the procedure. TECHNIQUE: After a vaginal hysterectomy, if the surgeon is struggling to safely complete a salpingo-oophorectomy, a natural orifice transluminal endoscopic surgery (NOTES) approach could be considered. A single port is placed in the vagina and after achieving pneumoperitoneum, an endoscope is introduced to perform a survey of the pelvis and lower abdomen. The salpingo-oophorectomy can then be completed under direct visualization by using conventional laparoscopic instruments through the vaginal port. EXPERIENCE: Salpingo-oophorectomy was successfully completed in six unembalmed cadavers and in two live patients. CONCLUSION: At the time of difficult vaginal salpingo-oophorectomy, the use of a NOTES approach could circumvent the need to convert to an abdominal route. It provides clear visualization of the entire pelvic and abdominal area and is technically feasible. PMID- 27400008 TI - Sharing of Snorting Straws and Hepatitis C Virus Infection in Pregnant Women. AB - OBJECTIVE: To evaluate possible modes of hepatitis C virus (HCV) acquisition in pregnant women found to be HCV-infected in the prenatal period and to assess transmission risk factors. METHODS: This was a prospective cohort study conducted from March 2014 through June 2015 involving the distribution of an anonymous survey to HCV-infected pregnant women that assessed for numerous modes of potential HCV transmission involving, intravenous drug use, blood transfusion, organ transplant, sexual contact, tattoos, and snorting drugs with a straw. Participants were drawn from our institutional obstetric high-risk clinic. Statistical analysis involved simple percentages and chi comparisons where appropriate; P<.05 was considered significant. To test biologic plausibility, snorting utensils confiscated by law enforcement authorities from patients not in this study were tested for the presence of human blood. RESULTS: A total of 189 HCV-infected pregnant patients completed the survey, and no approached patients declined. Of these, 136 (72%, 95% confidence interval [CI] 65-78%) admitted to intravenous drug use, of whom 89 (65%, 95% CI 57-73%) reported sharing needles. Of the 178 (94%, 95% CI 90-97%) who admitted snorting drugs, 164 (92%, 95% CI 87 96%) reported sharing straws. The difference between the proportion reporting sharing of snorting utensils compared with the proportion sharing intravenous drug use utensils was significant (P<.001). Twenty-nine patients (15%, 95% CI 11 21%) reported snorting drugs and sharing straws but denied any other risk factor except sexual contact. Of the 54 straws confiscated by law enforcement authorities, 13 (24%, 95% CI 13-38%) tested positive for the presence of human blood. CONCLUSION: Sharing snorting utensils (straws) in noninjection drug use may be an additional risk factor for HCV and other virus transmission. PMID- 27400009 TI - Abnormal Uterine Bleeding as the Presenting Symptom of Hematologic Cancer. AB - OBJECTIVE: To estimate the percentage of women with a hematologic cancer who present with abnormal uterine bleeding (AUB). METHODS: We performed a retrospective analysis of the records of women with hematologic malignancies treated at our institution from January 2002 through January 2016. Women with AUB as the chief presenting symptom were identified. RESULTS: Of the 10,682 women with hematologic malignancies, 38 had AUB as their chief presenting symptom. These women were young (median age 34 years), premenopausal, and otherwise healthy. The top four additional presenting symptoms were fatigue, dyspnea or shortness of breath, bruising or petechiae, and fever, with means (95% confidence interval) of 58% (41-74%), 42% (26-59%), 42% (26-59%), and 24% (11-40%), respectively. The complete blood count on initial presentation with AUB revealed that 33 (87%) women had anemia (mean hemoglobin level 8.6 g/dL) and 34 (89%) had thrombocytopenia (mean platelet count 81,000/microliter). Twelve (32%) women had neutropenia, eight (21%) women had normal white blood cell counts, and 18 (47%) women had leukocytosis. Thirty-three women (87%) were diagnosed with acute leukemia, one with myelodysplastic syndrome (3%) and four (11%) with chronic leukemia. CONCLUSION: We estimate the incidence of AUB as the chief presenting symptom is 3.6 cases per 1,000 women with hematologic cancer. These young, otherwise healthy women who present with acute, new-onset heavy menstrual bleeding in conjunction with thrombocytopenia or pancytopenia should be referred to hematology for evaluation of possible hematologic malignancy. PMID- 27400010 TI - Local and Systemic Inflammation in Localized, Provoked Vestibulodynia: A Systematic Review. AB - OBJECTIVE: To synthesize and critically evaluate all available evidence investigating whether localized, provoked vestibulodynia is associated with a specific inflammatory profile at both a local and a systemic level. DATA SOURCES: Comprehensive electronic searches were performed in MEDLINE, EMBASE, Scopus, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Collaboration databases, and ClinicalTrials.gov. The search strategy was developed using MeSH terms related to localized, provoked vestibulodynia, and inflammatory markers. METHODS OF STUDY SELECTION: Two independent investigators screened titles and abstracts and performed data extraction and risk of bias assessments. Studies were included if they reported at least one baseline inflammatory marker in women with localized, provoked vestibulodynia and compared them with healthy women. Reference lists from published reviews on localized, provoked vestibulodynia were screened for additional studies. TABULATION, INTEGRATION, AND RESULTS: There were 1,619 studies identified. Eighteen studies met the inclusion criteria, including 400 women with localized, provoked vestibulodynia and 212 healthy women in a control group. Risk of bias assessment revealed that the methodologic quality was generally low. Fifteen studies investigated local inflammation and three studies investigated systemic inflammation. On a local level, the number of mast cells expressed in vestibular tissues was greater in women with localized, provoked vestibulodynia expressed than in women in the control group. Several studies reported undefined inflammatory infiltrate in vestibular tissues to a greater level in women with localized, provoked vestibulodynia than in women in the control group. Systemically, levels of natural killer cells were lower in women with localized, provoked vestibulodynia than in women in the control group. There were no systemic differences in systemic interferon-alpha and interferon-upsilon levels between groups. CONCLUSION: There is limited and contradictory evidence regarding the characteristics of local and systemic inflammation in women with localized, provoked vestibulodynia. PMID- 27400011 TI - Rethinking the Bioethics of Pregnancy: Time for a New Perspective? AB - Within the realm of bioethics, the construction of pregnancy classically has focused on principle-based ethics, essentially separating maternal and fetal interests. Respect for maternal autonomy becomes distinct from an obligation of fetal beneficence, placing practitioners in complicated ethical situations when the goals of pregnant women may be at odds with the best health interests of the fetus as defined by both professional groups and society in general. As a result, clinical care is framed by an ethical "maternal-fetal conflict," with important downstream legal and policy consequences for the well-being of pregnant women. Developments in the social sciences highlight the value of attending to the biosocial realm that a pregnant woman inhabits rather than relating to her and to her fetus as discrete entities. By understanding the needs, concerns, and context within which a woman lives, clinicians can practice an ethics of accompaniment. With a focus on an ethics of accompaniment, assumptions about the maternal moral responsibility to fetal health made by practitioners and society in general can directly affect not only clinical care, but also the way policy surrounding reproductive health is constructed and implemented. PMID- 27400012 TI - Duration of Oxytocin and Rupture of the Membranes Before Diagnosing a Failed Induction of Labor. AB - OBJECTIVE: To compare maternal and neonatal outcomes based on length of the latent phase during induction with rupture of membranes before 6 cm dilation. METHODS: This is a retrospective cohort study using data from the Consortium of Safe Labor study, including 9,763 nulliparous and 8,379 multiparous women with singleton, term pregnancies undergoing induction at 2 cm dilation or less with rupture of membranes before 6 cm dilation after which the latent phase ended. Outcomes were evaluated according to duration of oxytocin and rupture of membranes. RESULTS: At time points from 6 to 18 hours of oxytocin and rupture of membranes, the rates of nulliparous women remaining in the latent phase declined (35.9-1.4%) and the rates of vaginal delivery for those remaining in the latent phase at these time periods decreased (54.1-29.9%) Nulliparous women remaining in the latent phase for 12 hours compared with women who had exited the latent phase had significantly increased rates of chorioamnionitis (12.1% compared with 4.1%) and endometritis (3.6% compared with 1.3%) and increased rates of neonatal intensive care unit admission (8.7% compared with 6.3%). Similar patterns were present for multiparous women at 15 hours. CONCLUSION: Based on when neonatal morbidity increased, in an otherwise uncomplicated induction of labor with rupture of membranes, a latent phase after initiation of oxytocin of at least 12 hours for nulliparous women and 15 hours in multiparous women is a reasonable criterion for diagnosing a failed induction. PMID- 27400013 TI - Association of Baseline Proteinuria and Adverse Outcomes in Pregnant Women With Treated Chronic Hypertension. AB - OBJECTIVE: To assess the importance of baseline proteinuria in women treated for chronic hypertension during pregnancy. METHODS: This retrospective cohort study included women with chronic hypertension who received antihypertensive therapy in the first half of pregnancy and completed urine protein quantification before 20 weeks of gestation. Maternal and neonatal outcomes were analyzed according to the presence or absence of baseline proteinuria, defined as 300 mg or greater per 24 hours identified before 20 weeks of gestation. Frequencies of superimposed preeclampsia, preterm birth, and small-for-gestational-age neonates were further evaluated according to stratified urine protein excretion levels from less than 50 mg to greater than 1,000 mg/24 hours. RESULTS: Between January 2002 and December 2014, a total of 447 women met inclusion criteria. Of these, 56 (13%) had baseline proteinuria. Women with baseline proteinuria were statistically significantly more likely to develop superimposed preeclampsia (79% compared with 49%), deliver preterm (18% compared with 6% 30 weeks of gestation or less, 34% compared with 17% 34 weeks of gestation or less, and 48% compared with 26% less than 37 weeks of gestation), and deliver an small-for-gestational-age neonate (41% compared with 22% less than the 10th percentile, 20% compared with 9% less than the third percentile) when compared with women who did not have proteinuria (all P<.05). Furthermore, the rates of superimposed preeclampsia and small for gestational age were significantly increased as 24-hour protein excretion levels increased across stratified levels (P for trend .002 and .015, respectively). When proteinuria levels less than 300 mg/d were analyzed separately, a significant association was observed for rates of superimposed preeclampsia and preterm birth. CONCLUSION: In pregnant women with treated chronic hypertension, baseline proteinuria was significantly associated with increased rates of preeclampsia, preterm birth, and growth restriction-even at proteinuria values previously considered to be within normal range (less than 300 mg/d). PMID- 27400014 TI - Whose Choice? Developing a Unifying Ethical Framework for Conscience Laws in Health Care. AB - Since abortion became legal nationwide, federal and state "conscience clauses" have been established to define the context in which health professionals may decline to participate in contested services. Patients and health care providers may act according to conscience in making health care decisions and in deciding whether to abstain from or to participate in contested services. Historically, however, conscience clauses largely have equated conscience in health care with provider abstinence from such services. We propose a framework to analyze the ethical implications of conscience laws. There is a rich literature on the exercise of conscience in the clinical encounter. This essay addresses the need to ensure that policy, too, is grounded in an ethical framework. We argue that the ideal law meets three standards: it protects patients' exercise of conscience, it safeguards health care providers' rights of conscience, and it does not contradict standards of ethical conduct established by professional societies. We have chosen Illinois as a test of our framework because it has one of the nation's broadest conscience clauses and because an amendment to ensure that women receive consistent access to contested services has just passed in the state legislature. Without such an amendment, Illinois law fails all three standards of our framework. If signed by the governor, the amended law will provide protections for patients' positive claims of conscience. We recommend further protections for providers' positive claims as well. Enacting such changes would offer a model for how ethics-based analysis could be applied to similar policies nationwide. PMID- 27400015 TI - Self-Administered Lidocaine Gel for Pain Control With First-Trimester Surgical Abortion: A Randomized Controlled Trial. AB - OBJECTIVE: To compare pain control at various time points during first-trimester surgical abortion using a patient-administered lidocaine gel compared with a traditional lidocaine paracervical block. METHODS: We conducted a randomized controlled trial of women undergoing surgical abortion at less than 12 weeks of gestation in an outpatient setting. The primary outcome was pain at cervical dilation as measured on a 100-mm visual analog scale. A sample size of 142 participants was planned to detect a 15-mm or greater difference on the 100-mm visual analog scale with 90% power and a significance level of .025, adding 10% for participant dropout and protocol violations. Participants received either 12 mL of a 1% lidocaine paracervical block or 20 mL of a self-administered, 2% lidocaine gel 20-30 minutes before procedure initiation. Secondary outcomes included anticipated pain, baseline pain, pain with speculum and tenaculum placement, pain after suction aspiration, and pain 30-45 minutes postoperatively. RESULTS: From April to October 2015, a total of 142 women were enrolled (68 in the paracervical block group, 69 in the gel group, and five not analyzed as a result of participant withdrawal). Sociodemographic characteristics were similar between groups. The mean pain score with cervical dilation was 60 mm (95% confidence interval [CI] 54-66) in the paracervical block group and 64 mm (95% CI 59-69) in the gel group (P=.3). There was no significant difference between mean pain scores at any time points measured. CONCLUSION: Self-administration of lidocaine gel before first-trimester surgical abortion is noninferior to a traditional paracervical lidocaine block and should be considered as an alternative, noninvasive approach to pain control for first-trimester surgical abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02447029. PMID- 27400016 TI - Outcomes of Pregnancies Complicated by Preterm Premature Rupture of Membranes Between 20 and 24 Weeks of Gestation. AB - OBJECTIVE: To assess the natural history and contemporary outcomes in pregnancies complicated by previable preterm premature rupture of membranes (PROM). METHODS: Retrospective study of all women with a singleton or twin pregnancy admitted to a single tertiary referral center who experienced preterm PROM between 20 and 23 6/7 weeks of gestation during 2004-2014 and underwent expectant management. Women electing termination of pregnancy and pregnancies complicated by major fetal anomalies were excluded. Severe neonatal morbidity was defined as a composite of bronchopulmonary dysplasia, severe neurologic injury, or severe retinopathy of prematurity. Long-term follow-up to a corrected age of 18-21 months was available for the majority of surviving neonates. RESULTS: Of the 140 neonates born to women with previable preterm PROM during the study period, 104 were eligible for the study. Overall 51 (49.0%, 95% confidence interval [CI] 39.4-58.6%) newborns survived to discharge, of whom 24 (47.1%, 95% CI 33.4-60.8%) experienced severe neonatal morbidity. The overall rate of long-term morbidity among surviving neonates was 23.3% (95% CI 11.7-34.9%) and was significantly higher among neonates who previously experienced severe neonatal morbidity compared with those who did not (39.1% compared with 10.0%, P=.04). The only two factors that were significantly associated with overall survival and survival without severe neonatal morbidity were gestational age at preterm PROM of 22 weeks or greater (adjusted odds ratio [OR] 12.2, 95% CI 3.3-44.8 and adjusted OR 4.8, 95% CI 1.2 19.3, respectively) and a latency period of greater than 7 days (adjusted OR 10.1, 95% CI 3.2-31.6, and adjusted OR 6.7, 95% CI 2.2-21.0, respectively). Expectant management was associated with maternal risks including placental abruption (17.3%, 95% CI 10.0-24.6%) and sepsis (4.8%, 95% CI 0.7-8.9%). CONCLUSION: Expectant management in pregnancies complicated by previable preterm PROM between 20 and 23 6/7 weeks of gestation is associated with an overall neonatal survival rate of 49.0%, high risk of short- and long-term severe morbidity among survivors, and carries considerable maternal risks. PMID- 27400017 TI - What Is New in Estrogen Agonists and Antagonists?: Best Articles From the Past Year. AB - This month we focus on current research in estrogen agonists and antagonists. Dr. Stovall discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in Box 1 on this page, along with direct links to the abstracts. PMID- 27400018 TI - Hepatitis C Virus Screening in Pregnancy: Is It Time to Change Our Practice? PMID- 27400019 TI - Effect of Different Dialysis Methods on Cellular Immunity Function of Maintenance Haemodialysis Patients. AB - Background: The study of the effect of different dialysis methods on cellular immune function of maintenance haemodialysis (MHD) patients should provide theoretical support for deciding on the best method of blood purification that effectively improves cellular immune function of haemodialysis patients. Subjects and Method: Sixty MHD patients were randomly divided into three groups that respectively received treatment of haemodialysis (HD), high flux haemodialysis (HFHD) and haemodiafiltration (HDF). Peripheral blood T lymphocyte subsets [CD4+, CD8+, CD25+ (mIL-2R) and CD4+/CD8+ ratio] and serum interleukin (IL)-2 and soluble IL-2 receptor (sIL-2R) levels were detected before dialysis and 4, 24 and 48 hours after dialysis in all cases. Results: Compared with the HD group, CD4+ and CD25+ cells, CD4+/CD8+ ratio and IL-2 level increased but sIL-2R level decreased in the HFHD and HDF groups at four hours without statistical significance (p > 0.05) and at 24 and 48 hours after dialysis with statistical significance (p < 0.05), while CD8+ cells had no change after dialysis (p > 0.05). Compared with the HFHD group, CD4+ and CD25+ cells, CD4+/CD8+ ratio, and IL-2 level increased but sIL-2R level decreased in the HDF group at four and 24 hours without statistical significance (p > 0.05) and at 48 hours after dialysis with statistical significance (p < 0.05), while CD8+ cells had no change after dialysis (p > 0.05). Conclusion: The results indicate that HD can briefly improve the cellular immune function of MHD patients, while MHD and HFHD can improve it continuously, with HDF having the best effect. PMID- 27400020 TI - Tibial impacts and muscle activation during walking, jogging and running when performed overground, and on motorised and non-motorised treadmills. AB - PURPOSE: To examine tibial acceleration and muscle activation during overground (OG), motorised treadmill (MT) and non-motorised treadmill conditions (NMT) when walking, jogging and running at matched velocities. METHODS: An accelerometer recorded acceleration at the mid-tibia and surface EMG electrodes recorded rectus femoris (RF), semitendinosus (ST), tibialis anterior (TA) and soleus (SL) muscle activation during OG, MT and NMT locomotion whilst walking, jogging and running. RESULTS: The NMT produced large reductions in tibial acceleration when compared with OG and MT conditions across walking, jogging and running conditions. RF EMG was small-moderately higher in the NMT condition when compared with the OG and MT conditions across walking, jogging and running conditions. ST EMG showed large and very large increases in the NMT when compared to OG and MT conditions during walking whilst SL EMG found large increases on the NMT when compared to OG and MT conditions during running. The NMT condition generated very large increases in step frequency when compared to OG and MT conditions during walking, with large and very large decreases during jogging and very large decreases during running. CONCLUSIONS: The NMT generates large reductions in tibial acceleration, moderate to very large increases in muscular activation and large to very large decreases in cycle time when compared to OG and MT locomotion. Whilst this may decrease the osteogenic potential of NMT locomotion, there may be uses for NMTs during rehabilitation for lower limb injuries. PMID- 27400021 TI - Dyadic Empathy Predicts Sexual and Relationship Well-Being in Couples Transitioning to Parenthood. AB - Becoming a new parent is typically a time of great joy, yet it is also marked by significant declines in sexual and relationship functioning. Dyadic empathy, a combination of perspective taking and empathic concern for one's romantic partner, may facilitate sexual and relationship quality for new parents. The purpose of this study was to examine the associations between dyadic empathy and sexual satisfaction, relationship adjustment, and sexual desire in a sample of first-time parents. Couples (N = 255) with an infant aged three to 12 months completed an online survey assessing dyadic empathy, sexual satisfaction, relationship adjustment, and sexual desire. Data were analyzed using multilevel analyses guided by the actor-partner interdependence model. When new mothers and fathers reported greater dyadic empathy, both they and their partners reported higher sexual satisfaction and relationship adjustment. New mothers who reported higher dyadic empathy also had higher sexual desire, although when they had more empathic partners new mothers reported lower sexual desire. Results remained significant after controlling for potential challenges unique to the postpartum period (e.g., fatigue, breastfeeding), as well as relationship duration. Targeting dyadic empathy in interventions aimed at helping couples transition to parenthood may promote the maintenance of sexual and relationship well-being. PMID- 27400022 TI - Effects of insecticides on a phytotelmata-breeding amphibian. AB - Information on the impact of pesticides on amphibian species breeding in phytotelmata (water bodies within plants) is totally lacking. The aim of the present study was to assess the impact of the insecticide malathion on larvae of Phyllodytes luteolus. Individuals were exposed to ecologically relevant concentrations of malathion (commercial formulation) for 16 d under laboratory conditions. Malathion had a lethal effect that allowed the authors to hypothesize that phtytotelmata-breeding species are likely as vulnerable to pollution as pond breeders. Environ Toxicol Chem 2017;36:422-428. (c) 2016 SETAC. PMID- 27400023 TI - Prevalence of frailty and associated factors in Korean older women: The KLoSA study. AB - The purpose of this study was to identify the prevalence of frailty in older women and its associated factors using data from the Korean Longitudinal Study of Aging (KLoSA). The level of frailty was moderate/severe in 20.2% of the women. Age, socioeconomic status, and depressive symptoms were significantly associated with all levels of frailty. Sensory function and grip strength were associated with both mild and moderate/severe frailty. The only factors associated with moderate/severe frailty were marriage status and regular exercise. Understanding the risk factors of frailty may help health care providers to deliver tailored interventions to prevent this condition and its adverse outcomes. PMID- 27400024 TI - Competition between the Direct Exchange Interaction and Superexchange Interaction in Layered Compounds LiCrSe2, LiCrTe2, and NaCrTe2 with a Triangular Lattice. AB - Physical properties of new S = 3/2 triangular-lattice compounds LiCrSe2, LiCrTe2, and NaCrTe2 have been investigated by X-ray diffraction and magnetic measurements. These compounds crystallize in the ordered NiAs-type structure, where alkali metal ions and Cr atoms stack alternately. Despite their isomorphic structures, magnetic properties of these three compounds are different; NaCrTe2 has an A-type spin structure with ferromagnetic layers, LiCrTe2 is likely to exhibit a helical spin structure, and LiCrSe2 shows a first-order-like phase transition from the paramagnetic trigonal phase to the antiferromagnetic monoclinic phase. In these compounds and the other chromium chalcogenides with a triangular lattice, we found a general relationship between the Curie-Weiss temperature and magnetic structures. This relation indicates that the competition between the antiferromagnetic direct d-d exchange interaction and the ferromagnetic superexchange interaction plays an important role in determining the ground state of chromium chalcogenides. PMID- 27400025 TI - Evaluation of validity of the new diabetic foot ulcer assessment scale in Indonesia. AB - We developed a new assessment tool for diabetic foot ulcers because no such tool specifically for diabetic foot ulcer exists. The diabetic foot ulcer assessment scale (DFUAS) has 11 domain items. The minimum and maximum scores on this scale are 0 and 98, respectively; higher scores indicate more severe wounds. The aim of this study was to evaluate the concurrent validity, construct validity and predictive validity of DFUAS in Indonesia. A prospective cohort study was conducted on patients with diabetic foot ulcer at Kitamura wound clinic in Indonesia. A total of 62 patients with 70 diabetic foot ulcers were assessed with DFUAS tool, Bates-Jensen wound assessment tool (BWAT), and pressure ulcer scale for healing (PUSH). Concurrent validity was determined by correlation of the DFUAS total score with the external criterion (BWAT, PUSH, and wound surface area). A comparison between the total DFUAS score and chronic wound status was made to determine construct validity. We also analyzed 41 wounds that were followed for 4 weeks to evaluate predictive validity. The correlation coefficient total scores of the DFUAS against the BWAT, PUSH, and wound surface area were 0.92, 0.87, and 0.82, respectively. The comparison of the total DFUAS score with chronic wound status was p < 0.001. The predictive validity test indicated that a DFUAS cutoff score of 12 produced the best balance of sensitivity, specificity, positive predictive value, and negative predictive value (89%, 71%, 86%, and 77%, respectively). In conclusion, the newly developed DFUAS is a valid tool for assessing diabetic foot ulcers. PMID- 27400026 TI - Contrasting ecosystem CO2 fluxes of inland and coastal wetlands: a meta-analysis of eddy covariance data. AB - Wetlands play an important role in regulating the atmospheric carbon dioxide (CO2 ) concentrations and thus affecting the climate. However, there is still lack of quantitative evaluation of such a role across different wetland types, especially at the global scale. Here, we conducted a meta-analysis to compare ecosystem CO2 fluxes among various types of wetlands using a global database compiled from the literature. This database consists of 143 site-years of eddy covariance data from 22 inland wetland and 21 coastal wetland sites across the globe. Coastal wetlands had higher annual gross primary productivity (GPP), ecosystem respiration (Re ), and net ecosystem productivity (NEP) than inland wetlands. On a per unit area basis, coastal wetlands provided large CO2 sinks, while inland wetlands provided small CO2 sinks or were nearly CO2 neutral. The annual CO2 sink strength was 93.15 and 208.37 g C m-2 for inland and coastal wetlands, respectively. Annual CO2 fluxes were mainly regulated by mean annual temperature (MAT) and mean annual precipitation (MAP). For coastal and inland wetlands combined, MAT and MAP explained 71%, 54%, and 57% of the variations in GPP, Re , and NEP, respectively. The CO2 fluxes of wetlands were also related to leaf area index (LAI). The CO2 fluxes also varied with water table depth (WTD), although the effects of WTD were not statistically significant. NEP was jointly determined by GPP and Re for both inland and coastal wetlands. However, the NEP/Re and NEP/GPP ratios exhibited little variability for inland wetlands and decreased for coastal wetlands with increasing latitude. The contrasting of CO2 fluxes between inland and coastal wetlands globally can improve our understanding of the roles of wetlands in the global C cycle. Our results also have implications for informing wetland management and climate change policymaking, for example, the efforts being made by international organizations and enterprises to restore coastal wetlands for enhancing blue carbon sinks. PMID- 27400027 TI - Simplifungin and Valsafungins, Antifungal Antibiotics of Fungal Origin. AB - The targets of antifungal antibiotics in clinical use are more limited than those of antibacterial antibiotics. Therefore, new antifungal antibiotics with different mechanisms of action are desired. In the course of our screening for antifungal antibiotics of microbial origins, new antifungal antibiotics, simplifungin (1) and valsafungins A (2) and B (3), were isolated from cultures of the fungal strains Simplicillium minatense FKI-4981 and Valsaceae sp. FKH-53, respectively. The structures of 1 to 3 including their absolute stereochemistries were elucidated using various spectral analyses including NMR and collision induced dissociation (CID)-MS/MS as well as chemical approaches including modifications to the Mosher's method. They were structurally related to myriocin. They inhibited the growth of yeast-like and zygomycetous fungi with MICs ranging between 0.125 and 8.0 MUg/mL. An examination of their mechanisms of action by the newly established assay using LC-MS revealed that 1 and 2 inhibited serine palmitoyltransferase activity, which is involved in sphingolipid biosynthesis, with IC50 values of 224 and 24 nM, respectively. PMID- 27400028 TI - Tailored educational supportive care programme on sleep quality and psychological distress in patients with heart failure: A randomised controlled trial. AB - BACKGROUND: Up to 74% of patients with heart failure report poor sleep in Taiwan. Poor symptom management or sleep hygiene may affect patients' sleep quality. An effective educational programme was important to improve patients' sleep quality and psychological distress. However, research related to sleep disturbance in patients with heart failure is limited in Taiwan. OBJECTIVES: To examine the effects of a tailored educational supportive care programme on sleep disturbance and psychological distress in patients with heart failure. DESIGN: randomised controlled trial. PARTICIPANTS AND SETTING: Eighty-four patients with heart failure were recruited from an outpatient department of a medical centre in Taipei, Taiwan. Patients were randomly assigned to the intervention group (n=43) or the control group (n=41). METHODS: Patients in the intervention group received a 12-week tailored educational supportive care programme including individualised education on sleep hygiene, self-care, emotional support through a monthly nursing visit at home, and telephone follow-up counselling every 2 weeks. The control group received routine nursing care. Data were collected at baseline, the 4th, 8th, and 12th weeks after patients' enrollment. Outcome measures included sleep quality, daytime sleepiness, anxiety, and depression. RESULTS: The intervention group exhibited significant improvement in the level of sleep quality and daytime sleepiness after 12 weeks of the supportive nursing care programme, whereas the control group exhibited no significant differences. Anxiety and depression scores were increased significantly in the control group at the 12th week (p<.001). However, anxiety and depression scores in the intervention group remained unchanged after 12 weeks of the supportive nursing care programme (p>.05). Compared with the control group, the intervention group had significantly greater improvement in sleep quality (beta=-2.22, p<.001), daytime sleepiness (beta=-4.23, p<.001), anxiety (beta=-1.94, p<.001), and depression (beta=-3.05, p<.001) after 12 weeks of the intervention. CONCLUSION: This study confirmed that a supportive nursing care programme could effectively improve sleep quality and psychological distress in patients with heart failure. We suggested that this supportive nursing care programme should be applied to clinical practice in cardiovascular nursing. PMID- 27400029 TI - Effects of self-management support programmes on activities of daily living of older adults: A systematic review. AB - BACKGROUND: The ability of older adults to carry out activities of daily living and to adapt and to manage their own life decreases due to deterioration of their physical and cognitive condition. Nurses and other health care professionals should support the self-management ability of older adults to prevent activities of daily living dependence and increase the ability to adapt and to self-manage the consequences of living with a chronic condition. OBJECTIVE: To gain insight into the evidence of the effects of self-management support programmes on the activities of daily living of older adults living at home. DESIGN: A systematic literature review of original research publications. DATA SOURCES: Searches were performed in PubMed, CINAHL, PsychInfo, EMBASE and the Cochrane Central Register of Controlled Trials (in February 2016). No limitations were applied regarding date of publication, language or country. REVIEW METHODS: Publications were eligible for this review on condition that they described a self-management support programme directed at adults of on average 65 years or older, and living in the community; used a randomized control group design; and presented information about the effects on activities of daily living. The methodological quality of the included studies was independently assessed by the authors using the quality criteria for reviews of the Cochrane Effective Practice and Organisation of Care Review Group. A best evidence synthesis was performed using guidelines provided by the Cochrane Collaboration Back Review Group. RESULTS: A total of 6246 potentially relevant references were found. After screening the references, 12 studies with a randomized controlled trial design were included. The methodological assessment of the 12 studies indicated variations in the risk of bias from low (n=1) to unclear (n=3) and high (n=8). Although there was considerable variation in study population, intervention characteristics and measurement instruments used, most studies (n=11) showed effects of self management support programmes on the activities of daily living of older adults. CONCLUSIONS: There is a moderate level of evidence that self-management support programmes with a multi-component structure, containing disease-specific information, education of knowledge and skills and, in particular, individually tailored coaching, improve the activities of daily living of older adults. Further research is required to gain insight into the most appropriate context and approach of self-management support interventions targeting activities of daily living of older adults living in the community. PMID- 27400030 TI - Particle Deposition onto People in a Transit Venue. AB - Following the release of an aerosolized biological agent in a transit venue, material deposited on waiting passengers and subsequently shed from their clothing may significantly magnify the scope and consequences of such an attack. Published estimates of the relevant particle deposition and resuspension parameters for complex indoor environments such as a transit facility are nonexistent. In this study, measurements of particle deposition velocity onto cotton fabric samples affixed to stationary and walking people in a large multimodal transit facility were obtained for tracer particle releases carried out as part of a larger study of subway airflows and particulate transport. Deposition velocities onto cotton and wool were also obtained using a novel automated sampling mechanism deployed at locations in the transit facility and throughout the subway. The data revealed higher deposition velocities than have been previously reported for people exposed in test chambers or office environments. The relatively high rates of deposition onto people in a transit venue obtained in this study suggest it is possible that fomite transport by subway and commuter/regional rail passengers could present a significant mechanism for rapidly dispersing a biological agent throughout a metropolitan area and beyond. PMID- 27400032 TI - Effects of parenting quality on adolescents' personality resemblance to their parents. The TRAILS study. AB - This study considers the development of resemblance between 741 adolescents and their biological parents, across six NEO-PI-R personality traits known to be important in psychological problems: anger-hostility, impulsiveness, vulnerability, assertiveness, excitement-seeking, and self-discipline. We modelled the association between perceived parental warmth and rejection at age eleven and personality resemblance to parents at about age sixteen. Parenting experienced during early adolescence was related to the degree and direction in which adolescents resembled their parents five years later in life. Rejection, especially from fathers, significantly predicted a smaller resemblance to both the parents. Girls were more strongly affected by parental quality than boys, and there was some indication that adolescents responded in opposite ways to parenting from mothers and fathers. This study is a first step in uncovering the complex interplay between parenting, gender, and the current generation's ability to develop personality traits independent from the previous generation. PMID- 27400031 TI - Association between FGF23, alpha-Klotho, and Cardiac Abnormalities among Patients with Various Chronic Kidney Disease Stages. AB - BACKGROUND: Several experimental studies have demonstrated that fibroblast growth factor 23 (FGF23) may induce myocardial hypertrophy via pathways independent of alpha-Klotho, its co-factor in the induction of phosphaturia. On the other hand, few studies have clearly demonstrated the relationship between FGF23 level and left ventricular hypertrophy among subjects without chronic kidney disease (CKD; i.e., CKD stage G1 or G2). PURPOSE: To investigate the data from 903 patients admitted to the cardiology department with various degrees of renal function, including 234 patients with CKD stage G1/G2. METHODS AND RESULTS: Serum levels of full-length FGF23 and alpha-Klotho were determined by enzyme immunoassay. After adjustment for sex, age, and estimated glomerular filtration rate (eGFR), the highest FGF23 tertile was significantly associated with left ventricular hypertrophy among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 as compared with the lowest FGF23 tertile, and the association retained significance after further adjustment for serum levels of corrected calcium, inorganic phosphate, and C-reactive protein, as well as diuretic use, history of hypertension, and systolic blood pressure. FGF23 was also associated with low left ventricular ejection fraction among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 after adjusting for age, sex, eGFR, corrected calcium, and inorganic phosphate. On the other hand, compared with the highest alpha-Klotho tertile, the lowest alpha-Klotho tertile was associated with left ventricular hypertrophy and systolic dysfunction only among patients with CKD stage G3b and stage G3a, respectively. CONCLUSIONS: An association between FGF23 and cardiac hypertrophy and systolic dysfunction was observed among patients without CKD as well as those with CKD after multivariate adjustment. However, the association between alpha-Klotho and cardiac hypertrophy and systolic dysfunction was significant only among patients with CKD G3b and G3a, respectively. PMID- 27400035 TI - The temporal relationship between diabetes and cancer: A population-based study. AB - BACKGROUND: Diabetes is associated with an increased risk of several cancers; however, greater detection of cancer around the time of diabetes diagnosis may partly contribute to this relationship. The goal of the current study was to explore the temporal relationship between diabetes and cancer incidence. METHODS: The authors conducted a retrospective, population-based cohort study of >1 million adults living in Ontario, Canada to evaluate the association between diabetes diagnosis and the incidence of cancer in 3 time periods: within the 10 years before a diabetes diagnosis, within the first 3 months after a diabetes diagnosis, and from 3 months to 10 years after a diabetes diagnosis. RESULTS: Individuals with diabetes were significantly more likely to have been diagnosed with cancer within the 10 years before a diabetes diagnosis compared with individuals without diabetes (odds ratio, 1.23; 95% confidence interval [95% CI], 1.19-1.27). Cancer incidence also was found to be significantly higher in individuals with diabetes within the 3-month period after a diabetes diagnosis (hazard ratio, 1.62; 95% CI, 1.52-1.74), whereas the risk was not found to be elevated in the later period (hazard ratio, 0.97; 95% CI, 0.95-0.98). Similar trends were noted for individual cancers. CONCLUSIONS: The results demonstrated that individuals with diabetes had a significantly higher risk of most cancers, which was limited to the time periods before and immediately after a diabetes diagnosis. The highest risk period was observed within the first 3 months after a diabetes diagnosis, suggesting a partial role of detection bias in the apparent relationship between diabetes and cancer. Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2731-2738. (c) 2016 American Cancer Society. PMID- 27400033 TI - Improved Performance of Electroplated CZTS Thin-Film Solar Cells with Bifacial Configuration. AB - Annealing in S vapor greatly improves the performance of electroplated Cu2 ZnSnS4 (CZTS) solar cells based on the bifacial configuration of Al-doped ZnO (AZO, front contact)/ZnO/CdS/CZTS/indium tin oxide (ITO, back contact), as compared to H2 S annealing in our previous works. S-vapor annealing does not cause severe damage to the conductivity of the ITO back contact. The highest device efficiency of 5.8 % was reached under 1 sun illumination from the AZO side. The well preformed devices based on the ITO back contact demonstrate smaller series resistances and better fill factors, as compared to our substrate-type devices using Mo back contacts. An interfacial reaction at the ITO back contact has been revealed in experiments, which contributes to the formation of SnO2 -enriched interfacial layer and diffusion of In from ITO into CZTS through the Sn sites. Incorporation of In does not significantly change the optical and structural properties or the grain size of CZTS absorbers. PMID- 27400036 TI - Comparative density functional theory and density functional tight binding study of arginine and arginine-rich cell penetrating peptide TAT adsorption on anatase TiO2. AB - We present a comparative density functional theory (DFT) and density functional tight binding (DFTB) study of geometries and electronic structures of arginine (Arg), arginine adsorbed on the anatase (101) surface of titania in several adsorption configurations, and of an arginine-rich cell penetrating peptide TAT and its adsorption on the surface of TiO2. Two DFTB parameterizations are considered, tiorg-0-1/mio-1-1 and matsci-0-3. While there is good agreement in the structures and relative energies of Arg and peptide conformers between DFT and DFTB, both adsorption geometries and energies are noticeably different for Arg adsorbed on TiO2. The tiorg-0-1/mio-1-1 parameterization performs better than matsci-0-3. We relate this difference to the difference in electronic structures resulting from the two methods (DFT and DFTB) and specifically to the band alignment between the molecule and the oxide. We show that the band alignment of TAT and TiO2 modeled with DFTB is qualitatively correct but that with DFT using the PBE functional is not. This is specific to the modeling of large molecules where the HOMO is close to the conduction band of the oxide. We therefore report a case where the approximate DFT-based method - DFTB (with which the correct band structure can be effectively obtained) - performs better than the DFT itself with a functional approximation feasible for the modeling of large bio-inorganic interfaces, i.e. GGA (as opposed to hybrid functionals which are impractical at such a scale). Our results highlight the utility of the DFTB method for the modeling of bioinorganic interfaces not only from the CPU cost perspective but also from the accuracy point of view. PMID- 27400037 TI - Identification and characterization of d-arabinose reductase and d-arabinose transporters from Pichia stipitis. AB - d-xylose and l-arabinose are the major constituents of plant lignocelluloses, and the related fungal metabolic pathways have been extensively examined. Although Pichia stipitis CBS 6054 grows using d-arabinose as the sole carbon source, the hypothetical pathway has not yet been clarified at the molecular level. We herein purified NAD(P)H-dependent d-arabinose reductase from cells grown on d-arabinose, and found that the enzyme was identical to the known d-xylose reductase (XR). The enzyme activity of XR with d-arabinose was previously reported to be only 1% that with d-xylose. The kcat/Km value with d-arabinose (1.27 min-1 mM-1), which was determined using the recombinant enzyme, was 13.6- and 10.5-fold lower than those with l-arabinose and d-xylose, respectively. Among the 34 putative sugar transporters from P. stipitis, only seven genes exhibited uptake ability not only for d-arabinose, but also for d-glucose and other pentose sugars including d xylose and l-arabinose in Saccharomyces cerevisiae. PMID- 27400039 TI - Travel Accidents and Sports Teams. PMID- 27400040 TI - Letters. PMID- 27400041 TI - A need to know. PMID- 27400042 TI - Brief reports. PMID- 27400045 TI - Infectious Mononucleosis In Athletes Earn Continuing Medical Education Credits Through the Pages of The Physician and Sportsmedicine. PMID- 27400044 TI - The Common Roots of Saints and Athletes. PMID- 27400046 TI - Cme credit quiz. PMID- 27400047 TI - The Stress of Coaching. AB - Like many other professions, coaching precipitates psychophysiological stress. Moreover, the authors found that there may be considerable stress on the coach of any sport, not just the major ones. PMID- 27400048 TI - Physical Training During Pregnancy and Lactation. AB - Do pregnant or lactating women risk impairing their or their infants' health by strenuously exercising? This study adds some interesting insights. PMID- 27400049 TI - Lack of Fitness a Source of Chronic Ills in Women. PMID- 27400050 TI - Exercise Prescription: A Practitioner's View. AB - An exercise prescription need not be grim, says the author, and he describes a flexible program that is more enjoyable, and just as beneficial, as the strictly regimented ones. PMID- 27400052 TI - Small-Town Doctor Provides Big-Time Care. PMID- 27400051 TI - Skateboarding: The Spill-and-Skill Sport. PMID- 27400053 TI - A Crash Course in Skiing Fundamentals. PMID- 27400054 TI - Treatment of Hip Pointers. PMID- 27400057 TI - A Preliminary Research into Clinical Semi-permeability Tolerance in the Field of Dental Rehabilitation. AB - Objective: To study clinical semi-permeability tolerance level in the field of dental restoration. Method: Vita 95 enamel porcelain powder was adopted and 6.0% used as the control transmissivity. Discoid porcelain plates with different transmissivity, namely increasing transmissivity (0.25%, 0.5%, 1.0%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4% and 4.5%) and decreasing transmissivity (-0.25%, -0.5%, -1.0%, -1.5%, -2%, -2.5%, -3% and -3.5%) were made. Forty observers judged these according to six grades: same, similar, slightly different, visibly different, recognizable and significantly different, and under the observation conditions of a neutral grey background and 45 degrees /0 degrees lighting. The judgment results were analysed statistically. Results: When the transmissivity of the control porcelain plates was 6.032%, and the transmissivity of test porcelain plates decreased by 1% or increased by 3%, observers could find slight differences between the test samples and the control samples. When transmissivity of test samples decreased by 2.5% or increased by 4.5%, observers thought that the two porcelain plates belonged to different orders of magnitude. Conclusions: Under the experimental conditions, the upper and lower limits of clinical semi permeability tolerance were 3% and 1%, respectively. PMID- 27400058 TI - Understanding Disease Tolerance and Resilience. AB - Our first ever Open Highlights explores recent Open Access research into the complex relationship between host and pathogen during the course of an infection, and the factors that determine its eventual outcome. PMID- 27400059 TI - Antioxidant enzyme activities as biomarkers of fluvial biofilm to ZnO NPs ecotoxicity and the Integrated Biomarker Responses (IBR) assessment. AB - The presence of ZnO nanoparticles (ZnO NPs) in natural waters has raised concerns about their environmental impacts, but the potential influences of ZnO NPs on fluvial biofilm have not been reported. In this study, the utility of antioxidant enzyme activities (AEA) as biomarkers of fluvial biofilm to ZnO NPs toxicity and a method that combines AEA into an index of "Integrated Biomarker Responses (IBR)" were studied. Compared with the absence of ZnO NPs, scanning electron microscopy (SEM) images revealed that a large amount of ZnO NPs were adsorbed onto biofilm and these NPs exerted adverse effects on the viability of bacteria in biofilm. The production of reactive oxygen species (ROS) with high concentrations (30 and 100mg/L) of ZnO NPs exposure reached to 184% and 244% of the control, while no cell leakage and membrane damage were observed. After exposure to ZnO NPs for 0.25 and 3 days, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR), glutathione peroxidase (GSH-Px) were significantly increased, respectively. At the end of exposure period (21 days), the AEA with the presence of 1mg/L ZnO NPs exposure were comparable to the control, while most of those in high concentrations of ZnO NPs were decreased. The results of IBR showed that the biofilm can adapt to 1mg/L ZnO NPs exposure, while be seriously damaged by 30 and 100mg/L ZnO NPs after 3 and 0.25 days. IBR can be used as an appropriate evaluation system of the toxicity effects of ZnO NPs on fluvial biofim. PMID- 27400060 TI - Risk assessment of three fluoroquinolone antibiotics in the groundwater recharge system. AB - Three fluoroquinolone antibiotics agents (FQs) in groundwater and reclaimed water have been investigated in Changzhou and Beijing, China. The occurrence of ofloxacin (OFL), enrofloxacin (ENR) and norfloxacin (NOR) is in nanograms per liter and has 100% frequency. The concentration order of FQs in reclaimed water is NOR>OFL>ENR, whilst the order in groundwater is NOR>ENR>OFL. And then the single and mixture adsorption-desorption have been studied and showed that (i) silty clay loam has higher sorption capacity than loamy sand, (ii) competitive adsorption exists when the three selected FQs coexist, (iii) ENR has a significantly priority sorption to NOR, whilst OFL has a least sorption among the mixture, (iv) there is no significant difference between the desorption results of mixture and the indivdual compound in relatively low concentration, (v) the formed chemical bonds and the irreversible combination of adsorption point are the significant influential factors for explaining desorption hysteresis of the selected FQs. Based on the above study, transport model and risk quotient have been performed, and the calculated risk quotient reveals that: (i) the selected FQs risk order in reclaimed water is OFL>ENR>NOR, (ii) in groundwater, OFL and ENR pose a higher risk than NOR no matter whether considering the long time groundwater recharge. This study will help policy makers to decide which FQs need to be covered in the priority substance lists defined in legislative frameworks. PMID- 27400061 TI - Oxidative stress and antioxidant responses to increasing concentrations of trivalent chromium in the Andean crop species Chenopodium quinoa Willd. AB - Quinoa (Chenopodium quinoa Willd), an ancient Andean seed crop, exhibits exceptional nutritional properties and resistance to abiotic stress. The species' tolerance to heavy metals has, however, not yet been investigated nor its ability to take up and translocate chromium (Cr). This study aimed to investigate the metabolic adjustments occurring upon exposure of quinoa to several concentrations (0.01-5mM) of CrCl3. Young hydroponically grown plants were used to evaluate Cr uptake, growth, oxidative stress, and other biochemical parameters three and/or seven days after treatment. Leaves accumulated the lowest amounts of Cr, while roots and stems accumulated the most at low and at high metal concentrations, respectively. Fresh weight and photosynthetic pigments were reduced only by the higher Cr(III) doses. Substantially increased lipid peroxidation, hydrogen peroxide, and proline levels were observed only with 5mM Cr(III). Except for a significant decrease at day 7 with 5mM Cr(III), total polyphenols and flavonoids maintained control levels in Cr(III)-treated plants, whereas antioxidant activity increased in a dose-dependent manner. Maximum polyamine accumulation was observed in 1mM CrCl3-treated plants. Even though alpha- and gamma-tocopherols also showed enhanced levels only with the 1mM concentration, tyrosine aminotransferase (TAT, EC 2.6.1.5) activity increased under Cr(III) treatment in a dose- and time dependent manner. Taken together, results suggest that polyamines, tocopherols, and TAT activity could contribute to tolerance to 1mM Cr(III), but not to the highest concentration that, instead, generated oxidative stress. PMID- 27400062 TI - How do toxic metals affect harmful cyanobacteria? An integrative study with a toxigenic strain of Microcystis aeruginosa exposed to nickel stress. AB - Nickel (Ni) is an essential metal for some organisms, but also a common toxic pollutant released into the water. Toxicity of Ni has not been completely established for cyanobacteria; for this reason, we evaluated the effect of sub inhibitory Ni concentrations on a toxigenic strain of Microcystis aeruginosa and on microcystins production. Population growth, photosynthetic pigments concentration, biomarkers, including antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPx], and superoxide dismutase [SOD]), as well as macromolecules (proteins, carbohydrates and lipids) were quantified; SEM and TEM observations were also performed. Population growth was affected starting at 3ugL(-1), and at 24ugL(-1) growth was completely inhibited; the 96-h Ni(2+) IC50 was 3.7ugL(-1). Ni exposure increased pigments concentration, augmented all the macromolecules, and increased activities of CAT and GPx; alterations on the internal cell structure were also observed. The integrated biomarker response revealed that Ni(2+) augmented the antioxidant response and the macromolecules content. Ni stress also increased microcystins production. M. aeruginosa was affected by Ni at very low concentrations, even lower than those established as safe limit to protect aquatic biota. Aside from the toxic effects produced in this cyanobacterium, stimulation to produce toxins could potentiate the environmental risks associated with water pollution and eutrophication. PMID- 27400063 TI - Arbuscular mycorrhiza detoxifying response against arsenic and pathogenic fungus in soybean. AB - Uptake of Arsenic (As) in plant tissues can affect metabolism, causing physiological disorders, even death. As toxicity, but also pathogen infections trigger a generalised stress response called oxidative stress; however knowledge on the response of soybean (Glycine max L.) under multiple stressors is limited so far. Arbuscular mycorrhizal fungi (AMF) enhance the tolerance of host plants to abiotic and biotic stress. Thus, we investigated the effects of the AMF Rhizophagus intraradices on soybean grown in As-contaminated soils as well as in the presence of the pathogen Macrophomina phaseolina (charcoal rot of the stem). Plant parameters and degree of mycorrhizal colonization under the different assessed treatments were analyzed. Content of As in roots and leaves was quantified. Increasing As level in the soil stopped plant growth, but promoted plant As uptake. Inoculation of soybean plants with M. phaseolina accentuated As effect at all physiological levels. In the presence of mycorrhizal symbiosis biomass dramatically increased, and significantly reduced the As concentration in plant tissues. Mycorrhization decreased oxidative damage in the presence of both As and the pathogen. Furthermore, transcription analysis revealed that the high affinity phosphate transporter from R. intraradices RiPT and the gene encoding a putative arsenic efflux pump RiArsA were up-regulated under higher As doses. These results suggest that R. intraradices is most likely to get involved in the defense response against M. phaseolina, but also in the reduction of arsenate to arsenite as a possible detoxification mechanism in AMF associations in soybean. CAPSULE ABSTRACT: R. intraradices actively participates in the soybean antioxidant defense response against arsenic stress and M. phaseolina infection. PMID- 27400064 TI - Modelling Lagged Associations in Environmental Time Series Data: A Simulation Study. AB - This study assesses two alternative approaches for investigating linear and nonlinear lagged associations in environmental time series data, comparing through simulations simple methods based on moving average summaries with more flexible distributed lag linear and nonlinear models. Results indicate that the latter provide estimates with no or low bias and close-to-nominal confidence intervals, even for long-lagged associations and in the presence of strong seasonal trends. Moving average models represent a viable alternative only in the presence of relatively short lag periods, and when the lag interval is correctly specified. In contrast, the use of moving averages to roughly approximate long and complex lag patterns, or the specification of an interval different than the actual lag period, can result in substantial biases. More flexible approaches based on distributed lag linear or nonlinear models provide noteworthy advantages, in particular when complex lagged associations are assumed. PMID- 27400065 TI - Protection of chickens vaccinated with combinations of commercial live infectious bronchitis vaccines containing Massachusetts, Dutch and QX-like serotypes against challenge with virulent infectious bronchitis viruses 793B and IS/1494/06 Israel variant 2. AB - Infectious bronchitis virus (IBV) is a coronavirus which affects chickens of all ages. IBV mainly causes respiratory disease but can also result in reduced weight gain, reduced egg production, increased frequency of abnormal eggs and increased rates of mortality. Vaccination is the most important way to control the disease. Nevertheless, novel strains of infectious bronchitis (IB) continue to emerge in the field. In order to respond promptly, combinations of existing IB vaccines are frequently tested to see whether they can provide cross-protection. The efficacy of a combination of vaccines based on Massachusetts, Dutch and QX-like IB strains against emerging IB Israel variant 2 and IB 793B strains was assessed by means of four challenge studies. At least 80% of the birds vaccinated with IB H120 (Mass type) combined with IB D274 (Dutch type) followed by a QX-like IB vaccine booster or vaccinated with a combination of IB H120, IB D274 and QX-like IB were protected against a challenge with IB 793B. In addition, IB 1263 (Mass type) boosted by QX-like IB showed an 85% protection following challenge with IB 793B. A combination of IB H120 and IB D274 boosted by QX-like IB vaccine conferred 70% protection whilst H120 and IB D274 combination on its own showed 61.1% protection against Israel variant 2 challenge. IB 1263 boosted by a QX-like IB vaccine showed 50% protection against IB Israel variant 2. Therefore, it can be concluded that a combination of the IB H120, IB D274 and QX-like IB confers broad protection against different non-related virulent IB strains. PMID- 27400066 TI - Yellow Fever Remains a Potential Threat to Public Health. AB - Yellow fever (YF) remains a serious public health threat in endemic countries. The recent re-emergence in Africa, initiating in Angola and spreading to Democratic Republic of Congo and Uganda, with imported cases in China and Kenya is of concern. There is such a shortage of YF vaccine in the world that the World Health Organization has proposed the use of reduced doses (1/5) during emergencies. In this short communication, we discuss these and other problems including the risk of spread of YF to areas free of YF for decades or never before affected by this arbovirus disease. PMID- 27400067 TI - What is the P-value anyway? PMID- 27400068 TI - Chronic graft versus host disease burden and late transplant complications are lower following adult double cord blood versus matched unrelated donor peripheral blood transplantation. AB - Adult umbilical cord blood transplantation (CBT) has emerged as an important option for patients lacking matched related (MRD) and matched unrelated donors (MUD). We compared chronic GVHD (cGVHD) incidence, immunosuppression burden and late infections and hospitalizations in consecutive patients undergoing CBT (n=51) versus peripheral blood MUD transplant (n=57) at our center between June 2009 and April 2014. At 3 years post transplantation, the cumulative incidence (CI) of moderate to severe cGVHD was 44% following MUD versus 8% following CBT (P=0.0006) and CI of any cGVHD was 68% following MUD versus 32% following CBT (P=0.0017). Median time to being off immunosuppression among CB patients was 268 days versus not reached among MUD patients (P<0.0001). Late infections and late hospitalized days were reduced in CB patients (P=0.1 and <0.001, respectively). Three-year CI of transplant-related mortality (TRM) and relapse as well as 3-year overall survival (OS) were similar following CB and MUD transplantation. We demonstrate a significantly lower incidence of cGVHD, immunosuppression burden and late complication rate following UCB versus peripheral blood MUD transplant without decreased OS, increased relapse or early TRM. Combined with the rapid availability of UCB, these findings have led our center to move primarily to UCB over peripheral blood MUD when a MRD is not available. PMID- 27400069 TI - Is there really a specific graft-versus-leukaemia effect? PMID- 27400070 TI - T2 relaxometry improves detection of non-sclerotic epileptogenic hippocampus. AB - OBJECT: The use of T2 relaxometry was investigated to detect non-sclerotic epileptogenic abnormality of the hippocampus in presurgical evaluation of temporal lobe epilepsy (TLE). METHODS: This prospective study included 30 patients who underwent hippocampectomy as part of surgical treatment of refractory TLE. Ten patients had structural epileptogenic lesions in the extra hippocampal temporal lobe. Twelve patients underwent intracranial electroencephalography (iEEG) study before surgery. Visual assessment of atrophy and increased T2 signal intensity, volumetry, and T2 relaxometry of hippocampus were performed pre-operatively using 3T magnetic resonance imaging, and compared with the neuropathological findings and iEEG findings. Magnetic resonance imaging of 30 age- and sex-matched healthy controls was used to establish normal values, which were defined as z score within 2. RESULTS: Visual assessment, volumetry, and T2 relaxometry detected hippocampal abnormalities on the surgical side in 16 (53%), 16 (53%), and 26 (87%) patients, respectively. Hippocampal volume loss was always associated with prolonged T2 relaxation time, and supported by histopathological diagnosis of HS in all cases except one. Hippocampal abnormality was detected only by T2 relaxometry in nine patients (30%). Pathological diagnosis of these cases included mild HS in one, microdysgenesis in one, and granule cell pathology in three. Four patients with normal hippocampal volume and T2 relaxation time had no HS or granule cell pathology. Prolonged T2 relaxation time was associated with medial temporal seizure onset in iEEG (p<0.05). CONCLUSIONS: T2 relaxometry improves the detection of non-sclerotic epileptogenic abnormality of the hippocampus. PMID- 27400071 TI - Sleep respiratory parameters in children with idiopathic epilepsy: A cross sectional study. AB - BACKGROUND: The aim of this study is to explore and compare through polysomnography respiratory sleep parameters between children with idiopathic epilepsy and healthy children. METHODS: Our cross-sectional study included 40 children with idiopathic epilepsy and 27 healthy children, who underwent overnight polysomnography. Data about sleep respiratory parameters were obtained and statistically analyzed. The level of statistical significance was set at 0.05. RESULTS: The prevalence of Obstructive Sleep Apnea Syndrome was significantly higher in the epilepsy group (35% vs 7.4%, p<0.01). Moreover, the odds ratio of an obstructive apnea index >=1 in the epilepsy group was 10.6 (95% Confidence Intervals: 3.08-37.08) in comparison to the control group. The mean value of the obstructive apnea-hypopnea index was significantly higher in children with epilepsy compared to healthy children (2.46+/-1.22 vs 1.21+/-0.83, p=0.027). The mean values of central apnea index and desaturation index were comparable between these two groups. Longest apnea duration was significantly higher in the group of poor seizure control. All other sleep respiratory variables did not differ significantly between children with poor and good seizure control and between children with generalized and focal epilepsy. CONCLUSIONS: Children with epilepsy seem to present more prominent sleep breathing instability in comparison to healthy children, which mainly includes a predisposition to obstructive respiratory events. More studies are needed to investigate the relationship between sleep apneas and seizure control. PMID- 27400072 TI - Oxygen-Evolving Porous Glass Plates Containing the Photosynthetic Photosystem II Pigment-Protein Complex. AB - The development of artificial photosynthesis has focused on the efficient coupling of reaction at photoanode and cathode, wherein the production of hydrogen (or energy carriers) is coupled to the electrons derived from water splitting reactions. The natural photosystem II (PSII) complex splits water efficiently using light energy. The PSII complex is a large pigment-protein complex (20 nm in diameter) containing a manganese cluster. A new photoanodic device was constructed incorporating stable PSII purified from a cyanobacterium Thermosynechococcus vulcanus through immobilization within 20 or 50 nm nanopores contained in porous glass plates (PGPs). PSII in the nanopores retained its native structure and high photoinduced water splitting activity. The photocatalytic rate (turnover frequency) of PSII in PGP was enhanced 11-fold compared to that in solution, yielding a rate of 50-300 mol e(-)/(mol PSII.s) with 2,6-dichloroindophenol (DCIP) as an electron acceptor. The PGP system realized high local concentrations of PSII and DCIP to enhance the collisional reactions in nanotubes with low disturbance of light penetration. The system allows direct visualization/determination of the reaction inside the nanotubes, which contributes to optimize the local reaction condition. The PSII/PGP device will substantively contribute to the construction of artificial photosynthesis using water as the ultimate electron source. PMID- 27400073 TI - Ectasia After Corneal Refractive Surgery: Nothing to SMILE About. PMID- 27400074 TI - Comparative Analysis of the Clinical Outcomes With a Monofocal and an Extended Range of Vision Intraocular Lens. AB - PURPOSE: To evaluate and compare the clinical outcomes with an aspheric monofocal intraocular lens (IOL) and an extended range of vision (ERV) IOL based on achromatic diffractive technology. METHODS: This was a prospective comparative study including 80 eyes undergoing cataract surgery with implantation of the monofocal Tecnis ZCB00 IOL (Abbott Medical Optics Inc., Santa Ana, CA) (monofocal group: 30 eyes of 15 patients) or the ERV Tecnis Symfony IOL (Abbott Medical Optics, Inc.) (ERV group: 50 eyes of 25 patients). Visual, refractive, contrast sensitivity, defocus curve, ocular optical quality (Optical Quality Analysis System; Visiometrics SL, Terrassa, Spain), and quality of life (National Eye Institute Refractive Error Quality of Life Instrument 42 Questionnaire) outcomes were evaluated during a 3-month follow-up. RESULTS: Significantly better postoperative uncorrected monocular and binocular distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities were found in the ERV group (P >= .013). Postoperative spherical equivalent was within +/-1.00 diopters in 94% and 100% of eyes in the ERV and the monofocal groups, respectively. Binocular UIVA and UNVA of 0.20 or better (Snellen 20/30) were observed in all cases in the ERV group and in 13.3% and 6.7% of eyes of the monofocal group, respectively. No significant differences among groups were observed in contrast sensitivity (P >= .156) or ocular optical quality parameters (P >= .084). In the monocular defocus curve, all visual acuities were better in the ERV group (P <= .002), except for the +0.50-diopter defocus level (P = .367). Significantly better scores were obtained for dependence on correction (P = .003) and suboptimal correction (P = .038) subscales in the ERV group. CONCLUSIONS: The extended range of vision IOL provides better distance, intermediate, and near visual acuity than the aspheric monofocal IOL, while maintaining the same level of visual quality. [J Refract Surg. 2016;32(7):436-442.]. PMID- 27400075 TI - Visual Performance and Rotational Stability of a Multifocal Toric Intraocular Lens. AB - PURPOSE: To evaluate the visual results, refractive predictability, rotational stability, and spectacle independence of patients who had cataract surgery with implantation of a diffractive multifocal toric intraocular lens (IOL) (Tecnis Multifocal Toric ZMT 150-400; Abbott Medical Optics, Santa Ana, CA). METHODS: This prospective study included 60 eyes of 30 patients with cataract and regular corneal astigmatism who had phacoemulsification with bilateral implantation of a Tecnis Multifocal Toric IOL. Over a 6-month follow-up period, the main outcome measures were uncorrected and corrected monocular and binocular distance (UDVA and DCVA), intermediate at 80 cm (UIVA and DCIVA), and near at 40 cm (UNVA and DCNVA) visual acuities, spherical equivalent (SE) refraction, residual astigmatism, rotational stability, defocus curves, contrast sensitivity, presence of photic phenomena, and use of spectacles. RESULTS: Results at 6 months showed mean UDVA of 0.07 +/- 0.1 logMAR (range: 0.3 to 0.0 logMAR), mean UIVA of 0.18 +/ 0.09 logMAR (range: 0.3 to -0.1 log-MAR, and mean UNVA of 0.03 +/- 0.09 logMAR (range: 0.2 to -0.1 logMAR). Refractive predictability was excellent with a mean SE of 0.05 +/- 0.47 diopters (D) (range: -0.75 to +1.00 D) and a mean refractive cylinder of -0.44 +/- 0.49 D (range: -1.25 to 0.00). Mean rotation was 3.18 degrees +/- 3.28 degrees . Photic phenomena were moderate or severe in 30% of patients. All patients were spectacle independent at the 6-month follow-up visit at all distances in this case series. CONCLUSIONS: The implantation of the Tecnis multifocal toric IOL in patients with cataract and corneal astigmatism provided excellent distance and near visual acuities with good intermediate visual acuity. Predictability of refractive results, rotational stability, and optical performance were excellent, allowing all patients in this series to achieve spectacle independence. [J Refract Surg. 2016;32(7):444-450.]. PMID- 27400076 TI - Clinical Outcomes After Cataract Surgery With a New Transitional Toric Intraocular Lens. AB - PURPOSE: To evaluate the visual outcomes of patients who underwent cataract surgery with implantation of a transitional toric monofocal intraocular lens (IOL) (Precizon Toric IOL, model 565; Ophtec BV, Groningen, The Netherlands). METHODS: In this prospective case series, 51 eyes of 39 patients with cataract and regular keratometric astigmatism between 1.00 and 4.50 diopters (D) that had phacoemulsification with implantation of a Precizon Toric IOL were included. Over a 4-month follow-up period, the main outcome measures were uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively), spherical equivalent (SE) refraction, astigmatism outcomes evaluated according to the Alpins method, the IOL's rotational stability, and higher order aberrations. RESULTS: At the 4-month follow-up visit, mean UDVA was 0.06 +/- 0.1 logMAR (range: 0.4 to -0.18 logMAR) (P < .001) and mean CDVA was -0.00 +/- 0.07 logMAR (range: 0.15 to -0.18 logMAR) (P < .001). UDVA was 0.3 logMAR or better in 50 (98%) eyes and 0.1 logMAR or better in 42 (82%) eyes. Mean SE refraction was 0.19 +/- 0.38 D (range: -1.13 to +0.50 D), with 44 (86%) eyes within +/-0.50 D of the attempted correction. Mean target induced astigmatism was 1.96 +/- 0.94 D (range: 0.70 to 4.50 D) and mean surgically induced astigmatism was 1.85 +/- 1.01 D (range: 0.07 to 4.64 D). Mean correction index was 0.87 (range: 0.07 to 2.29 D). Mean toric IOL axis rotation was 1.98 degrees +/- 1.78 degrees (range: 0 degrees to 7 degrees ). Ocular aberrometry was within normal values. CONCLUSIONS: The implantation of the Precizon Toric IOL in patients with cataract and corneal astigmatism provided excellent visual outcomes, predictability of refractive results, rotational stability, and good optical performance. [J Refract Surg. 2016;32(7):452-458.]. PMID- 27400077 TI - Corneal Collagen Cross-linking in Advanced Keratoconus: A 4-Year Follow-up Study. AB - PURPOSE: To analyze the safety and efficacy of standard corneal collagen cross linking (CXL) in advanced cases of progressive keratoconus after 4 years of follow-up. METHODS: A retrospective case series of patients with advanced progressive keratoconus (stages 3 and 4 of Amsler-Krumeich classification) underwent standard CXL treatment. The parameters examined were changes in uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), keratometry values (mean, flat, steep, and apical), pachymetry, and endothelial cell count at the baseline and at 12, 24, and 48 months postoperatively. RESULTS: Forty eyes of 40 patients were enrolled in the study. The mean patient age was 22.5 years (range: 15 to 37 years). Both mean UDVA and CDVA remained stable during the time points; no statistically significant change was noted. Although a slight reduction was observed in all keratometric readings, a statistically significant reduction was only reached in the apical keratometry (P = .037) at 4 years after CXL. A significant reduction in the corneal thickness was also found (ultrasonic: 388 +/- 49 to 379 +/- 48 MUm; slit-scanning: 362 +/- 48 to 353 +/- 51 MUm); however, this change was likely not clinically meaningful. Endothelial cell count was not significantly different at the end of the study. Treatment failure or progression was noted in two patients (5%) over the follow-up period. CONCLUSIONS: Standard CXL treatment was safe and able to stabilize both visual acuity and topographic parameters at 4 years of follow-up in eyes with advanced keratoconus. [J Refract Surg. 2016;32(7):459-464.]. PMID- 27400078 TI - Evaluation of the Robustness of Current Quantitative Criteria for Keratoconus Progression and Corneal Cross-linking. AB - PURPOSE: To evaluate the robustness of numerical indications of corneal cross linking by evaluating the inter-session reliability of recently used parameters of progression in keratoconus. METHODS: In this observational study, 100 eyes of 100 patients with keratoconus underwent analysis with the Sirius Scheimpflug Topography System (CSO, Firenze, Italy) by a single user. Two sessions (three scans per session) were performed 2 to 4 weeks apart. Cases having poor quality scans, recent visual deterioration, and ocular surgery were excluded. The corneal variables measured were thinnest point and apex characteristics (pachymetry, polar coordinates), volume, central simulated keratometry (flat, steep, average, astigmatism), central corneal thickness, maximum elevation (anterior, posterior), symmetry indices (front, back), and Baiocchi-Calossi-Versaci index. Intra-session (first session, all three measurements) and inter-session (one measurement from each session, selected randomly) statistics were computed. RESULTS: There were no significant differences in the six measurements for all variables (P > .05, analysis of variance). The intra-session and inter-session intraclass correlations were high (0.937 to 0.997) and within-subject standard deviations (Sw) were satisfactory (< 5 um for thickness, < 0.50 diopters [D] for curvature, and < 0.11 mm, < 5 degrees for polar coordinates). Inter-session repeatability (2.77 * Sw) was found to be satisfactory when compared to previously used central keratometric (> 1.00 D increase) or pachymetric (> 2%/> 5% decrease) guidelines to define progression. Apex power repeatability (1.24 D) was found to be poorer than previously used recommendations (1.00 D change). CONCLUSIONS: The criteria used to define keratoconus progression were satisfactory when compared to inter session reliability of corneal parameters. Because higher variability was noted at apex, its curvature repeatability cut-off may be raised to 1.25 D for identifying progressive keratoconus. [J Refract Surg. 2016;32(7):465-472.]. PMID- 27400079 TI - Epithelial Thickness Profile Changes Following Small Incision Refractive Lenticule Extraction (SMILE) for Myopia and Myopic Astigmatism. AB - PURPOSE: To evaluate the epithelial thickness profile changes following small incision refractive lenticule extraction (SMILE) and study their correlation with the amount of myopia corrected. METHODS: Epithelial thickness was measured in nine zones with spectral-domain anterior segment optical coherence tomography (SD OCT) across a 6-mm diameter preoperatively and at 1 day, 2 weeks, and 3 months postoperatively. The observed changes were correlated with the degree of myopia corrected. RESULTS: The study included 100 eyes from 50 eligible patients (32 females, 18 males) with a mean age of 24.4 +/- 2.8 years. Thirty-eight eyes underwent SMILE for low (spherical equivalent [SE] < -4.00 diopters [D]), 44 eyes for moderate (SE -4.00 to -6.00 D), and 18 eyes for high (SE > -6.00 to -10.00 D) myopia with 6.71 +/- 1.65, 6.82 +/- 0.21, and 6.44 +/- 0.2 mm optical zones, respectively. At 3 months, a statistically significant epithelial thickness increase was observed in the central zone (6.83% for low, 9.26% for moderate, and 12.7% for high myopia, P < .05 for all groups) and superior zone (3.98% for low, 7.82% for moderate, and 9.87% for high myopia) across all three groups, which correlated positively with the degree of myopia corrected (r(2) = 0.723 for central zone, r(2) = 0.585 for superior zone, P < .001 for both zones). None of the other zones showed any statistically significant changes at 3 months. Four eyes of two patients with high myopia (SE > -8.00 D) had regression due to significant epithelial thickening. CONCLUSIONS: Preliminary results suggest that epithelial thickness profile changes after SMILE may have an impact on the refractive outcome in the long-term postoperative period, especially in higher degrees of myopia. [J Refract Surg. 2016;32(7):473-478.]. PMID- 27400080 TI - Enhanced Combined Tomography and Biomechanics Data for Distinguishing Forme Fruste Keratoconus. AB - PURPOSE: To evaluate the performance of the Ocular Response Analyzer (ORA) (Reichert Ophthalmic Instruments, Depew, NY) variables and Pentacam HR (Oculus Optikgerate GmbH, Wetzlar, Germany) tomographic parameters in differentiating forme fruste keratoconus (FFKC) from normal corneas, and to assess a combined biomechanical and tomographic parameter to improve outcomes. METHODS: Seventy-six eyes of 76 normal patients and 21 eyes of 21 patients with FFKC were included in the study. Fifteen variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior and 37 ORA waveform parameters were tested. Sixteen tomographic parameters from Pentacam HR were tested. Logistic regression was used to produce a combined biomechanical and tomography linear model. Differences between groups were assessed by the Mann Whitney U test. The area under the receiver operating characteristics curve (AUROC) was used to compare diagnostic performance. RESULTS: No statistically significant differences were found in age, thinnest point, central corneal thickness, and maximum keratometry between groups. Twenty-one parameters showed significant differences between the FFKC and control groups. Among the ORA waveform measurements, the best parameters were those related to the area under the first peak, p1area1 (AUROC, 0.717 +/- 0.065). Among the investigator ORA variables, a measure incorporating the pressure-deformation relationship of the entire response cycle was the best predictor (hysteresis loop area, AUROC, 0.688 +/- 0.068). Among tomographic parameters, Belin/Ambrosio display showed the highest predictive value (AUROC, 0.91 +/- 0.057). A combination of parameters showed the best result (AUROC, 0.953 +/- 0.024) outperforming individual parameters. CONCLUSIONS: Tomographic and biomechanical parameters demonstrated the ability to differentiate FFKC from normal eyes. A combination of both types of information further improved predictive value. [J Refract Surg. 2016;32(7):479 485.]. PMID- 27400081 TI - Role of Age and Myopia in Simultaneous Assessment of Corneal and Extraocular Tissue Stiffness by Air-Puff Applanation. AB - PURPOSE: To assess the correlation of age and myopia with corneal and extraocular tissue stiffness derived from air-puff applanation using a composite viscoelastic model. METHODS: This retrospective, cross-sectional study evaluated 155 normal eyes (age range: 5 to 50 years) measured on Corvis ST (Oculus Optikgerate GmbH, Wetzlar, Germany). Manifest refraction spherical equivalent was also analyzed. A linear viscoelastic model that segregated corneal and extraocular tissue stiffness from the applanation deformation waveform was implemented. Corvis ST measured the total deformation (deformation amplitude waveform), which was simply the sum of corneal and extraocular tissue deformation. Age- and myopia-based multivariate analyses of variance between deformation parameters were performed after adjusting for intraocular pressure and central corneal thickness. Corvis ST corneal hysteresis was also calculated from the corneal deformation waveform. RESULTS: All myopia and age groups were matched for intraocular pressure and central corneal thickness. Extraocular tissue stiffness significantly increased with age (P = .03). Some other extraocular tissue deformation parameters also correlated with age, indicating age-related stiffening (P < .05). Corneal and extraocular tissue stiffness decreased with increasing myopia, but the trend was not significant (P = .10). Corvis ST corneal hysteresis increased with increasing age (P = .01) but not with increasing myopia (P = .61). CONCLUSIONS: Extraocular deformation parameters indicated stiffening of the extraocular tissues with age. Corneal deformation parameters were unaffected by age and myopia. Further studies with larger sample sizes are needed to clearly understand the effect of myopia on corneal and extraocular tissue stiffness. [J Refract Surg. 2016;32(7):486-493.]. PMID- 27400082 TI - Optimized Visual Outcome After Asymmetrical Multifocal IOL Rotation. AB - PURPOSE: To report improved visual outcome after rotation of an asymmetrical multifocal intraocular lens (IOL). METHODS: Case report. RESULTS: A 58-year-old patient underwent bilateral phacoemulsification with asymmetrical multifocal IOL implantation. Postoperative uncorrected distance visual acuity (UDVA) was 0.0 logMAR (20/20 Snellen) and uncorrected near visual acuity was 0.0 logMAR (20/20 Snellen) in both eyes. Quality of vision questionnaire scores for day and night were 5 and 7, respectively. The center of the multifocal IOL in the dominant eye was initially found to be 0.2 mm superotemporally displaced, increasing the percentage area of 'near-add' compared to 'distance-add' within the physiological pupil. Rotation of this IOL 120 degrees clockwise greatly improved the IOL centration within the pupil center and resulted in an immediate improvement in UDVA to -0.1 logMAR (20/16 Snellen) and quality of vision questionnaire scores to 8 and 9, respectively. CONCLUSIONS: Assessment of the centration of an asymmetrical multifocal IOL is important, particularly if there are dysphotoptic or other visual complaints. [J Refract Surg. 2016;32(7):494-496.]. PMID- 27400083 TI - Bilateral Ectasia After Femtosecond Laser-Assisted Small Incision Lenticule Extraction (SMILE). AB - PURPOSE: To describe a case of bilateral ectasia after small incision lenticule extraction (SMILE) in a patient with early keratoconus. METHODS: Case report. RESULTS: Bilateral SMILE was performed on a patient even though preoperative topographies showed changes indicating early keratoconus. The right eye underwent further photorefractive keratectomy enhancement 18 months later. The patient developed a bilateral corneal ectasia. CONCLUSIONS: This case underlines the importance of thorough preoperative assessment for possible keratoconus suspect changes with corneal topography to avoid postoperative ectasia. [J Refract Surg. 2016;32(7):497-500.]. PMID- 27400084 TI - Visual Quality After SMILE and LASEK for Mild to Moderate Myopia. PMID- 27400085 TI - Keratocytes and Mitomycin C. PMID- 27400086 TI - The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation induced oxidative stress in the hippocampus and striatum of rats. AB - Electromagnetic radiation (EMR) of cellular phones may affect biological systems by increasing free radicals and changing the antioxidant defense systems of tissues, eventually leading to oxidative stress. Green tea has recently attracted significant attention due to its health benefits in a variety of disorders, ranging from cancer to weight loss. Thus, the aim of the present study was to investigate the effect of EMR (frequency 900 MHz modulated at 217 Hz, power density 0.02 mW/cm2, SAR 1.245 W/kg) on different oxidative stress parameters in the hippocampus and striatum of adult rats. This study also extends to evaluate the therapeutic effect of green tea mega EGCG on the previous parameters in animals exposed to EMR after and during EMR exposure. The experimental animals were divided into four groups: EMR-exposed animals, animals treated with green tea mega EGCG after 2 months of EMR exposure, animals treated with green tea mega EGCG during EMR exposure and control animals. EMR exposure resulted in oxidative stress in the hippocampus and striatum as evident from the disturbances in oxidant and antioxidant parameters. Co-administration of green tea mega EGCG at the beginning of EMR exposure for 2 and 3 months had more beneficial effect against EMR-induced oxidative stress than oral administration of green tea mega EGCG after 2 months of exposure. This recommends the use of green tea before any stressor to attenuate the state of oxidative stress and stimulate the antioxidant mechanism of the brain. PMID- 27400087 TI - Facile Noninvasive Retinal Gene Delivery Enabled by Penetratin. AB - Gene delivery to the posterior segment of the eye is severely hindered by the impermeability of defensive barriers; therefore, in clinical settings, genomic medicines are mainly administered by intravitreal injection. We previously found that penetratin could transport the covalently conjugated fluorophore to the fundus oculi by topical instillation. In this study, gene delivery systems enabled by penetratin were designed based on electrostatic binding to target the retina via a noninvasive administration route and prepared with red fluorescent protein plasmid (pRFP) and/or poly(amidoamine) dendrimer of low molecular weight (G3 PAMAM). Formulation optimization, structure confirmation, and characterization were subsequently conducted. Penetratin alone showed limited ability to condense the plasmid but had powerful uptake and transfection by corneal and conjunctival cells. G3 PAMAM was nontoxic to the ocular cells, and when introduced into the penetratin-incorporated complex, the plasmid was condensed more compactly. Therefore, further improved cellular uptake and transfection were observed. After being instilled in the conjunctival sac of rats, the intact complexes penetrated rapidly from the ocular surface into the fundus and resided in the retina for more than 8 h, which resulted in efficient expression of RFP in the posterior segment. Intraocular distribution of the complexes suggested that the plasmids were absorbed into the eyes through a noncorneal pathway during which penetratin played a crucial role. This study provides a facile and friendly approach for intraocular gene delivery and is an important step toward the development of noninvasive gene therapy for posterior segment diseases. PMID- 27400088 TI - Phthalide Derivatives with Anticoagulation Activities from Angelica sinensis. AB - Two new phthalide derivatives, angesinenolides A and B (1 and 2), were isolated from the roots of Angelica sinensis. Their structures were elucidated using HRMS, NMR, and X-ray crystallographic data. Compound 1 is the first example of a phthalide trimer presumably formed through two [2+2] cycloaddition reactions. Compound 2 is a unique dimeric phthalide with a peroxy bridge between C-3a and C 6. Both phthalides were evaluated for in vitro anticoagulation activities. Compound 1 reduced the level of fibrinogen (FIB). Compound 2 significantly extended thrombin time and activated partial thromboplastin time, as well as markedly reduced the content of FIB. PMID- 27400089 TI - NOS3 27-bp and IL4 70-bp VNTR Polymorphisms Do Not Contribute to the Risk of Sickle Cell Crisis. PMID- 27400091 TI - The Management of Intracranial Aneurysms During Pregnancy: A Systematic Review. AB - Hemodynamic changes during pregnancy may favor the formation and rupture of intracranial aneurysms. Despite this risk, guidelines for managing intracranial aneurysms during pregnancy have not been clearly defined. The objective of this review is to describe the treatment options for pregnant women with intracranial aneurysms, and to report the maternal and fetal outcomes associated with different treatment strategies. A search of the literature was conducted using the PubMed database for the period January 1991 through June 2015. Aneurysm characteristics and management, pregnancy management, and maternal and fetal outcomes were evaluated. The most recent search was performed in June 2015. In total, 50 aneurysms (44 patients) were evaluated. Rupture was confirmed upon imaging in 36 aneurysms (72%), and most aneurysms ruptured during the third trimester (77.8%). Coil embolization was associated with a lower complication rate than clipping in patients with ruptured aneurysms (9.5% vs 23.1%). For patients with unruptured aneurysms, surgical management was associated with 31.9% fewer complications compared to no treatment. Most patients underwent Cesarean delivery (84%), and a combined neurosurgical-obstetrical procedure was used for 8 patients with ruptured aneurysms near term. Adverse outcomes were reported in 11.9% of children. Treatment of intracranial aneurysms during pregnancy is safe and effective. Furthermore, we suggest that coil embolization be considered a first line treatment over clipping for surgical management of the pregnant population. Going forward, we encourage the establishment of formal guidelines for managing intracranial aneurysms during pregnancy. PMID- 27400090 TI - Mental Reactivation and Pleasantness Judgment of Experience Related to Vision, Hearing, Skin Sensations, Taste and Olfaction. AB - Language acquisition is based on our knowledge about the world and forms through multiple sensory-motor interactions with the environment. We link the properties of individual experience formed at different stages of ontogeny with the phased development of sensory modalities and with the acquisition of words describing the appropriate forms of sensitivity. To test whether early-formed experience related to skin sensations, olfaction and taste differs from later-formed experience related to vision and hearing, we asked Russian-speaking participants to categorize or to assess the pleasantness of experience mentally reactivated by sense-related adjectives found in common dictionaries. It was found that categorizing adjectives in relation to vision, hearing and skin sensations took longer than categorizing adjectives in relation to olfaction and taste. In addition, experience described by adjectives predominantly related to vision, hearing and skin sensations took more time for the pleasantness judgment and generated less intense emotions than that described by adjectives predominantly related to olfaction and taste. Interestingly the dynamics of skin resistance corresponded to the intensity and pleasantness of reported emotions. We also found that sense-related experience described by early-acquired adjectives took less time for the pleasantness judgment and generated more intense and more positive emotions than that described by later-acquired adjectives. Correlations were found between the time of the pleasantness judgment of experience, intensity and pleasantness of reported emotions, age of acquisition, frequency, imageability and length of sense-related adjectives. All in all these findings support the hypothesis that early-formed experience is less differentiated than later-formed experience. PMID- 27400092 TI - Keyhole Transsylvian Resection of Infiltrative Insular Gliomas: Technique and Anatomic Results. AB - AIM: Insular gliomas have traditionally been approached through variations of large frontotemporal craniotomies exposing much of the Sylvian fissure. Due to the importance of many structures exposed by such an approach, a less-invasive approach to these lesions is a viable alternative for resection. We present the technique and results of our keyhole transsylvian approach to remove infiltrating insular tumors. MATERIAL AND METHODS: A small linear incision and keyhole craniotomy is planned under image guidance to open a transsylvian window. Using a combination of the microscope and endoscope, we remove the insula circumferentially outward. We present our results of 20 patients with gliomas confined to the insula evaluated with volumetric imaging analysis. RESULTS: There were 12 right-sided and 8 left-sided tumors. The median skin-to-skin operative time was 215 minutes. 15/20 patients were discharged from the hospital on or before post-operative day 3, with 5 of those going home the day after surgery. Greater than 90% of the tumor was removed in 18 of 20 cases, with an additional case achieving 89.5% resection. In no case was the residual tumor volume greater than 3 cc. Permanent weakness occurred in 2 patients (10%). Despite a significant number of left-sided tumors, temporary dysphasia occurred in only 1 patient (12.5%), which resolved by first follow up. CONCLUSION: Localized insular gliomas can be effectively removed through a minimally invasive approach without increasing the risk of neurological morbidity. This minimizes manipulation of uninvolved, potentially eloquent cortices, and minimizes damage to the overlying soft tissue. PMID- 27400093 TI - Prognostic Value of Angiogenesis and Survivin Expression in Patients with Glioblastoma. AB - AIM: Glioblastoma (GBM) is the most common and the most aggressive primary brain tumor with poor prognosis. We aimed to evaluate the association between immunohistochemical expression of survivin and angiogenic parameters (microvessel density and vascular pattern) in patients who underwent surgery for GBM. MATERIAL AND METHODS: The pathology reports and also clinical and follow-up data of patients with GBM were retrospectively evaluated. Control tissues were obtained from the archive for each antibody (Survivin, CD 34). Then, control staining of these antibodies was performed. Vessels were evaluated according to the standardized assessment of vascular pattern. RESULTS: Mean survival for classical vascular pattern was longer than bizarre vascular pattern (p < 0.001). The survival time of patients decreased with increasing score of survivin staining. There was a significant correlation between survivin and survival time (p < 0.001). There was no significant correlation between microvessel density and survival time (p > 0.05). CONCLUSION: With these findings, it is considered that high expression of survivin, bizarre vascular pattern and development of secondary GBM correlates with the low survival rates, however microvessel density has no correlation with the survival rates. Since only malignant cells express survivin, it might be a target protein for the development of novel therapies. PMID- 27400094 TI - Fully Endoscopic Resection of Intra-Axial Brain Lesions Using Neuronavigated Pediatric Anoscope. AB - AIM: To present a new simple disposable tubular retractor which provides fully endoscopic resections of the intraaxial brain lesions. MATERIAL AND METHODS: A total of 13 patients underwent surgical resection of an intraaxial brain lesion larger than 3 cm with a fully endoscopic approach using the navigation-guided pediatric anoscope. The anoscope was adapted to serve as a tubular retractor. All lesions were resected under endoscopic visualization and navigation guidance. There were 7 men and 6 women with a mean age of 49.6 years (range, 19-76 years). Lesion location was as follows: frontal (n=4), parietal (n=1), frontoparietal (n=2), temporal (n=2), and intraventricular (n=4). RESULTS: With the use of this technique, preoperative goals of surgery were met in all patients. Gross total resection of the lesions was achieved in 7 of 13 patients (53.8%), near-total resection in 3 patients (23.1%) and subtotal resection in 3 (23.1%) patients. The histological diagnosis included 2 metastases, 5 (38.5%) glioblastomas, 3 meningiomas, 2 low grade gliomas and one oligodendroglioma. There were no complications related to the surgical procedure. Duration of surgery ranged from 60 to 110 minutes, with an average 90 minutes. The average postoperative hospital stay was 2.7 days. CONCLUSION: Endoscopic resection of deep-seated brain lesions with the neuronavigated tubular retractor is a safe and an effective technique and may be a feasible alternative to conventional microsurgical or endoscope assisted methods in selected patients. The modified transparent plastic pediatric anoscope can be used as a tubular retractor and it is easy to apply, simple, lightweight, inexpensive and effective. PMID- 27400095 TI - Monitoring Ischemic Cerebral Injury in Spontaneously Hypertensive Rats by Diffusion Tensor Imaging. AB - AIM: We have applied diffusion tensor imaging (DTI) to interrogate microstructural changes in white matter integrity in a widely used middle cerebral artery occlusion (MCAO) model of cerebral ischemia. MATERIAL AND METHODS: We performed ex vivo DTI 35 days after 60 minutes transient focal ischemia in male spontaneously hypertensive rats and generated fractional anisotropy (FA), mean, axial and radial diffusivity maps. Regions of interest corresponding to external capsule (EC), corpus callosum (CC) and internal capsule (IC) were compared among sham and stroked rats. We compared tractographic projections of white matter fiber patterns and examined white matter integrity by Luxol fast blue histological analysis. We also determined infarct lesion volumes at 24 hours post-ischemia by T2-weighted magnetic resonance imaging (MRI) or at 35 days by histological staining with cresyl violet. RESULTS: We found alterations in EC and IC, but not CC, as represented by decreased FA and increased mean, axial and radial diffusivities. The size of the ischemic lesion detected subacutely by T2-weighted MRI or at 35 days by histological staining correlated with the decline in FA in the affected structures. Tractography revealed disruption of fiber trajectories through the EC and reorientation of fibers within the caudate/putamen of rats subjected to MCAO. Similarly, loss of white matter integrity in the EC and increased white matter density in the caudate/putamen along the infarct border zone was evidenced by Luxol fast blue staining. CONCLUSION: Diffusion tensor imaging therefore allows for monitoring of white matter injury and reorganization in hypertensive rats. PMID- 27400096 TI - Clinical and Angiographic Outcomes of Endovascular Treatment for Ruptured Posterior Circulation Cerebral Aneurysms. AB - AIM: To report the angiographic and clinical results achieved in endovascular treatment of ruptured posterior circulation cerebral aneurysms over a 3-year period. MATERIAL AND METHODS: A retrospective analysis of 45 patients was performed between June 2008 and June 2011. Clinical follow-up was achieved in all patients, with a mean duration of 17 months. Angiographic follow-up was obtained in 88.9% of cases, with a mean duration of 7.2 months. RESULTS: A clinical improvement, or stable outcome was achieved in all patients. There was one case of re-bleeding as a periprocedural complication 2 days after incomplete stent assisted coiling of a vertebral artery aneurysm. There was no death in our patients. In 40 of the 45 patients (88.9%), angiographic follow-up was obtained at a mean of 7.2 months (range, 1 to 24 months). Recurrences in 5 patients (12.5%) at 2 days, 3, 6, 8, and 13 months required re-treatment. CONCLUSION: Endovascular embolization is an attractive option for ruptured posterior circulation aneurysms with stable long-term outcome. This study confirmed that endovascular treatment is associated with low mobidity and mortality. However, re canalization may be observed up to 2 years after the initial obliteration. Long term follow-up with angiography is needed. PMID- 27400097 TI - Transarterial ONYX Embolization of Intracranial Dural Arteriovenous Fistulas in Adults. AB - AIM: To present our experience on transarterial treatment of dural arteriovenous fistulas (DAVFs) with ONYX in adult patients. MATERIAL AND METHODS: Between March 2008 and November 2012, 27 adult patients with DAVFs treated by transarterial ONYX embolization were included. Clinical data, including hospital records, operative reports, and angiograms, were reviewed and analyzed. RESULTS: Complete obliteration of the fistula was achieved in 16/27 (59.3%) patients after 32 intra arterial embolizations. One complication (3.7%) was transient hemiparesis. Follow up imaging, which was available for 16 fistulas with angiographic cures, showed no evidence of recurrence. At mean 14.5 months follow-up, 26 patients (96.3%) had GOS score of 5 and 1 patient (3.7%) had GOS score of 3. CONCLUSION: Transarterial ONYX embolization has become the main treatment for adult intracranial DAVFs and is associated with high safety and efficacy. PMID- 27400098 TI - Silk Device for the Treatment of Intracranial Aneurysms. Part 1: Peri-Procedural Results, Technical Aspects and Learning Curve. AB - AIM: We evaluated the procedural outcomes of intracranial aneurysm treatment with the Silk device and its relation with operator experience. We also detailed some technical points we learned throughout our experience. MATERIAL AND METHODS: One hundred and six consecutive patients with intracranial aneurysms treated using Silk (BaltExtrusion, Montmorency, France) stent between October 2010 and November 2013 were included. Patients were evaluated in terms of age, sex, aneurysm size, location, technical success, and adverse events. RESULTS: There were 106 patients (71 female) undergoing 116 procedures with a mean age of 49.8 (range: 3-78 years). Mean aneurysm size was 10.7+/-8.0 (range, 2-40 mm). Technical success of the procedures was 96.5%. Adverse event rate was 11.2%. Among adverse events, there were 4 adverse events without complications, 2 mild complications, 7 severe complications, 4 of which resulted with death. The adverse event rate was significantly higher during the first half of the operator's experience. The rate of adverse events seemed to stabilize after around 50 patients. Adverse events, regardless of the presence or absence of a clinical complication, were more frequent in aneurysms larger than 18.5 mm. CONCLUSION: Safety of flow-diverter (FD) placement for intracranial aneurysms increases with operator experience. Training programs in endovascular management of cerebrovascular diseases and relevant fellowship curricula must be adapted to include sufficient flow diverter experience. The learning curve needs to be kept in mind when studies comparing different FD devices or those comparing other treatments to FDS are planned. PMID- 27400099 TI - Silk Device for the Treatment of Intracranial Aneurysms, Part 2: Factors Related to Clinical and Angiographic Outcome. AB - AIM: To report patient and procedure-related factors affecting the angiographic and clinical outcome in patients treated with the Silk device. MATERIAL AND METHODS: All patients with intracranial aneurysms in whom treatment was attempted with the Silk flow diverter by our neurovascular team between October 2010 and November 2013 were included consecutively. The data was analyzed by an independent stroke neurologist not involved in the treatment of the patients. RESULTS: A total of 96 patients (64 female) with ages range from 3 to 78 were included in this study. We found that 54 of the patients were asymptomatic and 42 of them symptomatic, while 21 had a prior history of subarachnoid hemorrhage (SAH). Mean aneurysm size was 10.2 mm (range 2 to 40 mm). 2 patients died due to consequences of SAH. 3 patients developed visual decline on the follow-up, 2 of these were procedure-related. Symptomatic thromboembolic events were noted in 7 cases. Patients with aneurysms smaller than 13 mm had significantly less complications and higher occlusion rates. The complication rate was significantly high in patients admitted with symptoms. Adjunctive coiling had no impact on outcome. CONCLUSION: Safety and efficacy of flow diversion in this series was closely related to aneurysm size and presenting symptoms. A size cut-off for safety and efficacy has not been reported before and will be useful not only for future studies but also for patient counseling in daily practice. The futility of adjunctive coiling in this series calls for reappraisal of the current recommendations for this specific device. PMID- 27400100 TI - Effect of Simvastatin on Proliferation of Vascular Smooth Muscle Cells During Delayed Cerebral Vasospasm After Subarachnoid Hemorrhage. AB - AIM: To explore the effect of simvastatin on proliferation of vascular smooth muscle cells (VSMCs) during delayed cerebral vasospasm (dCVS) after subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: Thirty-six male New Zealand White rabbits were randomly divided into three groups: 1) Control group (n=12): given conventional breeding and normal sodium (0.9%) was injected twice into the cisterna magna. 2) SAH group (n=12): given conventional breeding and a SAH model was established. 3) Simvastatin + SAH group (n=12): given conventional breeding and simvastatin for one week, and then a SAH model was established. The first cerebral angiography was conducted before the first injection of sodium or autologous blood into the cisterna magna. The second angiography was done three days after the second injection. The ultrastructural pathology of the basilar artery was compared in three groups. The expression of platelet-derived growth factor-beta (PDGF-beta), proliferating cell nuclear antigen (PCNA) and alpha smooth muscle actin (alpha-SMA) in VSMCs was analysed by RT-PCR. RESULTS: Angiography examinations showed that the basilar artery was obviously contracted in the SAH group and dCVS was confirmed existence after blood injection into the cisterna magna twice. The thickness of VSMCs in the SAH group increased and the expression of PDGF-beta, PCNA, and alpha-SMA in SAH group were all increased compared to the control group (p < 0.05), and decreased while prophylactic giving simvastatin (p < 0.05). CONCLUSION: Simvastatin may relieve dCVS after SAH by inhibiting the proliferation of VSMCs. PMID- 27400101 TI - Predictors of Symptomatic Vasospasm After Subarachnoid Hemorrhage: A Single Center Study of 457 Consecutive Cases. AB - AIM: We set forth to identify predictors of symptomatic vasospasm in patients with subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: We used multivariate logistic regression analysis of the prospective, hospital based, single center register of the Department of Neurosurgery, University of Debrecen, Hungary. Evaluated patients' characteristics were: sex, age, Hunt-Hess grade on admission, location of aneurysm, thickness of blood clot on initial CT scan (Fisher grade), hypertension. RESULTS: Between 1987 and 2004, 567 SAH cases were registered, 457 were included in this study. Symptomatic vasospasm developed in 22.5% of the cases. In univariate analysis, Hunt-Hess grades 2 and 3 and female sex were predictive for symptomatic vasospasm. In multivariate analysis, female sex remained a significant predictor: OR: 1.8 (1.005-3.2). CONCLUSION: Women are at more danger of developing symptomatic vasospasm after subarachnoid hemorrhage. PMID- 27400102 TI - The Neuroprotective Effects of Resveratrol Preconditioning in Transient Global Cerebral Ischemia-Reperfusion in Mice. AB - AIM: This study was designed to elucidate the neuroprotective effect of resveratrol in a mouse model of bilateral common carotid artery occlusion (BCCAO). MATERIAL AND METHODS: Sixty male C57BL/6 mice, weighing 20-24 g, were used in our experiments. The mice were randomly assigned into three groups: control group, BCCAO group and BCCAO+Resveratrol group. Neurological score was assessed 24h, 48h, 72h after BCCAO, respectively. Hematoxylin and eosin (H&E) staining, NeuN and TUNEL were performed to detect the neuronal death and survival. The expression of Bcl-2, Bax, caspase-3, and cleaved caspase-3 were also detected to assess the anti-apoptotic effect of resveratrol by Western Blot. RESULTS: Resveratrol significantly improved neurological score in BCCAO mice. Besides, it attenuates neuronal apoptosis via increasing the expression of Bcl-2 and decreasing the expression of Bax, caspase-3, and cleaved caspase-3. Resveratrol promotes neuronal survival in mice subjected to BCCAO. CONCLUSION: Resveratrol is beneficial in the model of BCCAO, which is associated with its anti-apoptotic effect. PMID- 27400103 TI - Which Biomarker is most Effective to Determine Severity of Acute Head Trauma in the Experimental Animal Head Trauma Model? AB - AIM: Because of the need for effective method to determine the severity of head trauma, the importance of biomarkers is recognized recently. This study aims to analyze the values of sera levels of some biomarkers and the relation with their tissue levels in acute head injury. MATERIAL AND METHODS: In this study, rats were divided into three groups (mild head trauma, severe head trauma and control group). All rats were anaesthetized. Weightdrop method was used as trauma method. Blood samples were obtained five minutes after trauma when the acute effects of trauma occurred. Then whole brains of rats were excised. Levels of biomarkers were investigated in the sera samples and homogenized brain tissues biochemically. RESULTS: Significant differences in the sera GFAP (p=0.015) and insulin (p=0.011) levels were observed. Very significant difference in the sera nNOS level was observed. Extremely significant difference in the tissue IL-6 (p < 0.001) level was observed between all groups. CONCLUSION: Sera nNOS and tissue IL 6 are the best biomarkers to predict trauma severity. Sera GFAP and insulin are also capable to show trauma severity in the very acute period of postinjury. Tissue levels of the biomarkers except insulin are higher than their sera levels. PMID- 27400104 TI - A Very Quickly Prepared, Colored Silicone Material for Injecting into Cerebral Vasculature for Anatomical Dissection: A Novel and Suitable Material for both Fresh and Non-Fresh Cadavers. AB - AIM: Cadaveric studies have a great impact on neuroanatomy learning. Cadaver preparation may take a lot of effort, especially at the phase of intravascular color filling. The authors describe their silicone dye technique and a novel mixture which is self-curing, quick to prepare and easy to inject. MATERIAL AND METHODS: The first one of these processes is undoubtedly embalming and decapitation of the cadaver. If possible, the most appropriate time that should be preferred is immediately after the donor's death. Preparation for cadaveric dissection of the brain requires some fundamental steps that can be summarized into: a) Embalming and decapitation, b) Exposing, cannulization and irrigation of main vascular structures, c) Preparing colored silicone, d) Injection of colored silicone and staining the vascular tree, e) Sample maintenance RESULTS: Our method of preparation of silicone dye and injection enables neurosurgeons and anatomists to fill cerebral and dural vascular structures, and even diploic veins nicely in both fresh and aged cadaveric heads. Moreover, the main vascular structures and their branches in the lateral and third ventricles are painted remarkably beautifully. CONCLUSION: We tried to provide our experience about the preparation of head cadavers for anatomical dissection using a novel mixture of colored silicone that is very easy to prepare and inject with very satisfactory results. PMID- 27400105 TI - Comparison of Neuronavigation and Frame-Based Stereotactic Systems in Implanting Epileptic Depth Electrodes. AB - AIM: To investigate the application of neuronavigation in the implantation of depth electrodes in patients with epilepsy. MATERIAL AND METHODS: Thirty-six patients with epilepsy who were implanted with depth electrodes using neuronavigation were assessed for accuracy of implantation and associated complications. RESULTS: In the imaging navigation group, patients were implanted with 2-14 depth electrodes. The average number of implantations was 4.8 electrodes/case. The average implantation error was 2.03 +/- 0.98 mm, exhibiting no significant difference compared to the frame-based stereotactic group. In the imaging group, an average of 19.4 min was required to implant each electrode, which was significantly shorter than the time required in the frame group (34.5 min). The temporal lobe was elucidated as the factor that affects electrode implantation accuracy. One patient in the imaging group exhibited a small amount of bleeding, and one suffered from cerebrospinal fluid leakage; however, the overall complication rate in the imaging group was lower than that in the frame group. CONCLUSION: Imaging navigation provides better means of depth electrode implantation; its implantation accuracy is similar to that of the frame-based stereotactic method and it is less time consuming and causes less complications, and is especially suitable for stereoelectroencephalography, which requires multiple depth electrodes. PMID- 27400106 TI - Effect of Intrathecal Anti-Fibroblast Growth Factor-2 Antibodies on the Mechanical Allodynia and Activation of Spinal Cord Astrocytes in Rats. AB - AIM: To investigate the effect of intrathecal anti-fibroblast growth factor-2 (FGF-2) antibodies on the mechanical allodynia and activation of spinal cord astrocytes in a rat model of neuropathic pain. MATERIAL AND METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups (Each group=10 rats). Group A: Spared nerve injury (SNI) model and intrathecal phosphate-buffered saline (PBS); Group B: SNI model and intrathecal FGF-2 antibodies; Group C: Sham surgery and intrathecal PBS; Group D: Sham surgery and intrathecal basic FGF-2 antibodies. The paw withdrawal mechanical threshold (PWMT) was evaluated one day before the operation and at the 1, 4, 7, 14 and 21 days after the operation. Meanwhile, the expression of FGF-2, glial fibrillary acidic protein (GFAP) of astrocytes, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the L4~6 spinal cord segments were gauged at 21 days after the operation. RESULTS: SNI significantly induced the mechanical allodynia and markedly increased the number of FGF-2 and GFAP positive cells and the levels of TNF-alpha and IL-6 (p < 0.05). Intrathecal injection of FGF-2 antibodies suppressed the increase of FGF-2 and GFAP positive cells, and the levels of TNF-alpha and IL-6. These antibodies significantly attenuated SNI-induced mechanical allodynia in rats (p < 0.05). CONCLUSION: FGF-2 antibodies have the effect of analgesia on neuropathic pain in rats. PMID- 27400107 TI - Targeting Apoptosis Through Foxp1, and N-cadherin with Glatiramer Acetate in Chick Embryos During Neural Tube Development. AB - AIM: To demonstrate the effect of glatiramer acetate (GA) in chick embryos on neural tube (NT) development, and to explore its effects of Foxp1, apoptosis, and N-cadherin. MATERIAL AND METHODS: One hundred fertile, specific pathogen free eggs were divided into 5 groups for this study. The eggshell was windowed specifically at 24 hours of incubation. The embryos in Group 1 (n=20) were treated with 10 MUl physiological saline; in Group 2 the embryos (n=20) were given 10 MUl GA (equal to daily human therapeutic dose); 20 MUl GA (equal to twice daily human therapeutic dose) was injected to embryos in Group 3 (n=20); in Group 4 and 5, 30 MUl and 40 MUl GA were administered to the embryos (n=20) (equal to x3 and x4 daily human therapeutic dose, respectively). Each egg was re incubated for 24 hours more. Then, histological and immunohistochemical evaluation of the subjects were done. RESULTS: The embryos with NT defect showed FOXP1 expression without N- cadherin or staining with N-cadherin in another location in our study. We interpreted this result as GA leading to an NT closure defect by increasing FOXP expression. Moreover, we also showed the reverse relation between FOXP1 and N-cadherin at the immunohistochemical level for the first time. CONCLUSION: GA affects the spinal cord development through FOXP in the chick embryo model at high doses. PMID- 27400108 TI - Initial Discectomy Associated with Aging Leading to Adjacent Disc Disease and Recurrence. AB - AIM: Failure of surgery for lumbar disc herniation (LDH) can be commonly caused by recurrence. There are many debates regarding the risk factors of recurrent LDH (rLDH) and it is very difficult to define them because many clinical and complicated biomechanical parameters are involved. The purpose of study was to evaluate the long term result of re-discectomy for LDH at the same level and adjacent segments. MATERIAL AND METHODS: Between 1999 and 2009, 1898 cases were operated and 142 (6.4%) patients underwent re-discectomy following initial operation. The study included 65 patients who were operated for single level discectomy, and their charts were analyzed retrospectively. RESULTS: There were 33 (50.8%) women and mean age was 45.5 years (24-73 years). rLDH was diagnosed at the initial level in 40 (61.5%) but adjacent and/or opposite level herniation (with or without the first level) was found in the remaining 25 cases (39.1%). Recurrence at the same level (SLG) and adjacent level groups (ALG) were similar according to the clinical outcomes in follow-up (mean 34.1 months). Admission period after initial operation was also parallel in SLG and ALG (54.7 and 53.1 months, respectively). However, the mean age of ALG (49.4 years) was significantly higher (p<=0.05) than SLG (42.8 years). CONCLUSION: After discectomy, collapsed discs are biomechanically more stable than those with preserved disc heights, and responses to axial compression on intervertebral disc pressure produced deformations of adjacent levels despite limitations. Altered biomechanical loading next to a fusion resulted in ongoing degeneration with aging at the affected entire lumbar spine. PMID- 27400109 TI - Surgical Management of Osteoblastoma of the Spine: Case Series and Review of the Literature. AB - AIM: To describe the demographics, clinical and radiologic presentation, surgical considerations, and clinical outcomes associated with spinal osteoblastoma. MATERIAL AND METHODS: A spinal tumor database of 522 patients treated surgically at a single institution between January 2002 and June 2012 was analyzed and five patients with spinal osteoblastoma were identified and included in this study. Basic demographic and epidemiological data were recorded. Tumor characteristics, surgical parameters, and clinical follow-up data were noted. RESULTS: The mean follow-up was 21.9 months. There were four males and one female, and the mean age at diagnosis was 28.4 years. There was a mean reported symptom length of 26.4 months prior to diagnosis. There were three cervical lesions, one lumbar lesion, and one sacrococcygeal lesion. One patient was Enneking stage III and four patients were Enneking stage II. Based on spinal instability neoplastic score criteria, two patients were stable and three patients were potentially unstable. Four patients had intralesional gross total resections and one patient had an en bloc marginal resection. All patients remained neurologically stable or improved postoperatively. A single patient had recurrence of a previously resected osteoid osteoma with progression to osteoblastoma. CONCLUSION: Aggressive surgical resection of spinal osteoblastoma is suggested to minimize the risk of tumor recurrence, although this may still occur even with en bloc resection. Patients rarely present with preoperative spinal instability, but surgical fusion is often required due to removal of structural elements of the spine during resection. Of note, osteoid osteoma may progress to osteoblastoma in the spine despite prior resection. PMID- 27400110 TI - Long-Term Benefits of Percutaneous Anatomical Restoration of Vertebral Compression Fractures Linked to Malignancy. AB - AIM: To evaluate the efficacy, feasibility and safety of a percutaneous anatomical vertebral body reduction for the treatment of VCF (vertebral compression fracture) linked to malignancy. Vertebroplasty and percutaneous kyphoplasty have played essential roles in the treatment of painful vertebral metastasis, although there are few reports with long survival that have evaluated the long-term efficacy, adjacent fractures and vertebral body (VB) re-collapse associated with these procedures. We aimed to evaluate the longterm efficacy and the complications associated with malignancy and changes in spinal biomechanics. MATERIAL AND METHODS: The retrospective study examined 32 patients with osteolytic VCF due to malignant infiltration of the vertebral body. A visual analogue scale, the EQ5 and radiological analysis (i.e., X-ray and CT scan) were used to assess back pain, quality of life and complications. RESULTS: Statistically significant reductions in anterior and central vertebral body heights (6.2 mm-19.6 +/- 4.2 mm- and 5.8 mm- 16.7 +/- 7.8 mm-, respectively) that resulted in reductions of the regional Cobb angles exceeding 30% were observed. There was also a statistically significant improvement in quality of life. The average survival was longer than those reported in most published articles, and the average follow-up period was 30.9 months. CONCLUSION: Anatomical restoration (i.e., cortical ring reduction with endplate rebalancing) is potentially beneficial for a wellselected group of patients with spine metastases and long life expectancies because this procedure avoids the complications typical of these types of treatments (e.g., leakage, adjacent fractures and re-collapse). PMID- 27400111 TI - Surgical Management of Adult Reducible Atlantoaxial Dislocation, Basilar Invagination and Chiari Malformation with Syringomyelia. AB - AIM: To analyze retrospectively the surgical management of reducible atlantoaxial dislocation (AAD), basilar invagination (BI) and Chiari malformation (CHM) with syringomyelia through a single-stage posterior approach. MATERIAL AND METHODS: Forty-three patients with reducible AAD, BI and CHM with syringomyelia underwent surgery from January 2009 to January 2013. Intraoperative restoration followed by posterior decompression and plate-rod placement with occipital cortical screws and C2/C3 lateral mass cortical screws fixation devices were used in all patients. Results were recorded both pre- and postoperatively and these outcome measures included Nurick grading (NG) and radiology findings (atlantodental interval (ADI), space available for the spinal cord (SAC), interval between odontoid and Chamberlain's line (IOC), and the cervicomedullary angle (CMA)). RESULTS: Forty (93%) of the 43 patients were followed up. Thirty-six (90%) patients' symptoms improved and four (10%) stabilized. No patients became progressively worse. The difference between preoperative and postoperative Nurick grades was statistically significant. All patients achieved restoration, including thirty (75%) patients had full restoration and ten (25%) had part restoration. The size of syringomyelia was obviously decreased in 32 (80%) patients and stable in 8 (20%) patients. All radiology findings (ADI, IOC, SAC, CMA) showed significant changes from pre- to postoperative (p < 0.01). CONCLUSION: Intraoperative distraction, extension combined posterior decompression with use of plate-rod-screws occipitocervical fusion device is an effective method to treat AAD, BI and CHM with syringomyelia. PMID- 27400112 TI - The Biochemical, Histopathological and Clinical Comparison of the Neuroprotective Effects of Subcutaneous Adalimumab and Intravenous Methylprednisolone in an Experimental Compressive Spinal Cord Trauma Model. AB - AIM: To evaluate the neuroprotective effects of adalimumab in an experimental spinal cord injury model and compare them with those of the widely-used methylprednisolone. MATERIAL AND METHODS: Forty male Wistar rats were divided into 5 as the sham, trauma, adalimumab, methylprednisolone, and adalimumab+methylprednisolone groups. Only laminectomy was performed in the sham group. Laminectomy and trauma was performed to the trauma group but no treatment was given. A single dose of 40 mg/kg subcutaneous adalimumab was administered after the laminectomy and trauma to group 3. A single dose of intravenous 30 mg/kg methylprednisolone was administered right after laminectomy and trauma to group 4. Single doses of 40 mg/kg adalimumab and 30 mg/kg methylprednisolone were administered together after laminectomy and trauma to group 5. Serum malondialdehyde (MDA), TNF-alpha, IL-1beta and IL-6 levels were measured and sections were obtained for histopathological study at the end of the 7 < sup > th < /sup > day. RESULTS: MDA, TNF-alpha, IL-1beta and IL-6 levels in serum were significantly decreased in the adalimumab group with clinical and histopathological improvement not less than the methylprednisolone group. The serum MDA levels were similar when the two drugs were given together or separately but there was a statistically quite significant decrease in TNF-alpha, IL-1beta and IL-6 levels with concurrent use. Statistically significantly better results were obtained on histopathological evaluation with the use of both drugs together. CONCLUSION: This study revealed that adalimumab is as effective as methylprednisolone in compressive spinal cord injury in rats. PMID- 27400113 TI - Stent-Assisted Coil Embolization of a Transverse-Sigmoid Sinus Diverticulum Presenting with Pulsatile Tinnitus. AB - When tinnitus is pulse-synchronous, a vascular etiology is suggested. We present a case of persistent and troublesome pulsatile tinnitus caused by a transverse sigmoid sinus diverticulum that was endovascularly treated with stent-assisted coiling. A 39-yearold woman presented with a 4-year history of progressive pulsatile tinnitus involving the right ear. Slight pulsatile bruit was heard on the right mastoid bone by auscultation. Cerebral angiography demonstrated a diverticulum of the transverse-sigmoid sinus. The procedure was performed with an 8F guiding catheter (Cordis, USA) catheterized into the right sigmoid sinus. The diverticulum was completely coiled following deployment of a 5.5 mm-50 mm Leo stent. This patient awakened without any neurological deficit and with immediate resolution of her tinnitus. This case report describes a stent-assisted coil embolization of venous sinus diverticulum, which provides immediate resolution of pulsatile tinnitus. PMID- 27400114 TI - Fahr's Syndrome Associated with Multiple Intracranial Aneurysms: A Case Report. AB - Fahr's Syndrome is characterized by the presence of intracerebral, bilateral and symmetrical calcifications located in bilateral basal ganglia, thalamus, and cerebellum. The etiology is not exactly known. The authors reported a very rare case who had Fahr's Syndrome and intracerebral aneurysms simultaneously. The patient was female and presented with headache. Her examinations revealed aneurysms on the middle cerebral artery, internal carotid artery and ophthalmic artery. That is the first case reported in the literature having multiple intracranial aneurysms and Fahr's Syndrome together. PMID- 27400115 TI - Systematic Approach for Anterior Corpectomy through a Transthoracic Exposure. AB - While several approaches have been suggested for performing a transthoracic corpectomy of the thoracolumbar spine, the steep learning curve and high risk of operative morbidity often dissuades its use clinically. As a result, posterior approaches have been more frequently used, though transthoracic approaches often allow for improved access for more complete decompression of the spinal cord. Additionally, the transthoracic approach allows for more complete removal of vertebral body lesions along with better access for reconstruction of the anterior column. Here we describe a distinct nine-step thoracolumbar corpectomy technique via a transthoracic approach. We include a description of one patient with one-year follow-up to further illustrate the surgical approach and relevant surgical anatomy. We have used this technique for maximal bi-pedicular decompression afforded by the lateral approach. We discuss key anatomical considerations, perioperative techniques and potential complications of the operation. The presented nine-step transthoracic corpectomy technique is a safe method for providing adequate neurological decompression and vertebral body tumor removal. PMID- 27400116 TI - Two novel members of the LhrC family of small RNAs in Listeria monocytogenes with overlapping regulatory functions but distinctive expression profiles. AB - Multicopy small RNAs (sRNAs) have gained recognition as an important feature of bacterial gene regulation. In the human pathogen Listeria monocytogenes, 5 homologous sRNAs, called LhrC1-5, control gene expression by base pairing to target mRNAs though 3 conserved UCCC motifs common to all 5 LhrCs. We show here that the sRNAs Rli22 and Rli33-1 are structurally and functionally related to LhrC1-5, expanding the LhrC family to 7 members, which makes it the largest multicopy sRNA family reported so far. Rli22 and Rli33-1 both contain 2 UCCC motifs important for post-transcriptional repression of 3 LhrC target genes. One such target, oppA, encodes a virulence-associated oligo-peptide binding protein. Like LhrC1-5, Rli22 and Rli33-1 employ their UCCC motifs to recognize the Shine Dalgarno region of oppA mRNA and prevent formation of the ribosomal complex, demonstrating that the 7 sRNAs act in a functionally redundant manner. However, differential expression profiles of the sRNAs under infection-relevant conditions suggest that they might also possess non-overlapping functions. Collectively, this makes the LhrC family a unique case for studying the purpose of sRNA multiplicity in the context of bacterial virulence. PMID- 27400118 TI - The suitability of Sanders' model for calculation of the propulsive force generated by the hands during sculling motion. AB - This study examined whether Sanders' model is suitable for estimating accurately the propulsive force generated by the hands' motion in swimming comparing the calculated force obtained using the model and the measured force during an actual propulsive action. The measured and calculated forces were obtained from 13 swimmers who, while tethered, performed a sculling motion in a prone position for the purpose of displacing the body by moving it forward. Kinematic analyses were conducted to obtain the calculated force, while the measured force was obtained via the use of a load cell. The calculated force was lower than the measured force and accounted for only a small part of the variation in the measured force. The forces could not be used interchangeably, and there were fixed and proportional differences between them. Consequently, this study indicates that Sanders' model is not suitable for estimating accurately the propulsive force generated by the swimmer's hands during sculling motion. However, research that integrates analyses from different approaches could result in improvements to the model that would render it applicable for estimating the propulsive forces during movements that are characterised by directional changes of the hands. PMID- 27400117 TI - ACR Appropriateness Criteria(r) Management of Recurrent Endometrial Cancer. AB - OBJECTIVES: In women with endometrial carcinoma (EC), tumor recurrences tend to occur in the 2- to 3-year period following surgical staging. Management of disease recurrence in EC poses significant challenges. These patients represent a heterogenous group where histologic subtypes, previous adjuvant management, interval since completion of adjuvant therapy, and size and site(s) of disease recurrence all have important implications on salvage therapies and prognosis. No randomized controlled trials have been published to determine optimal management in this group of patients. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients. METHODS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. RESULTS: Five clinical variants were developed to address common scenarios in the management of women with recurrent EC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings. CONCLUSIONS: In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with recurrent EC. PMID- 27400119 TI - Hunter-gatherer genomics: evolutionary insights and ethical considerations. AB - Hunting and gathering societies currently comprise only a small proportion of all human populations. However, the geographic and environmental diversity of modern hunter-gatherer groups, their inherent dependence on ecological resources, and their connection to patterns of behavior and subsistence that represent the vast majority of human history provide opportunities for scientific research to deliver major insights into the evolutionary history of our species. We review recent evolutionary genomic studies of hunter-gatherers, focusing especially on those that identify and functionally characterize phenotypic adaptations to local environments. We also call attention to specific ethical issues that scientists conducting hunter-gatherer genomics research ought to consider, including potential social and economic tensions between traditionally mobile hunter gatherers and the land ownership-based nation-states by which they are governed, and the implications of genomic-based evidence of long-term evolutionary associations with particular habitats. PMID- 27400120 TI - Manual Therapy Practices of Sobadores in North Carolina. AB - OBJECTIVES: This analysis provides a description of the manual-therapy elements of sobadores practicing in North Carolina, using videotapes of patient treatment sessions. DESIGN: Three sobadores allowed the video recording of eight patient treatment sessions (one each for two sobadores, six for the third sobador). Each of the recordings was reviewed by an experienced chiropractor who recorded the frequencies of seven defined manual-therapy elements: (1) treatment time; (2) patient position on treatment surface; (3) patient body part contacted by the sobador; (4) sobador examination methods; (5) primary treatment processes; (6) sobador body part area referencing patient; and (7) adjunctive treatment processes. RESULTS: The range of treatment time of 9-30 min was similar to the treatment spectra that combine techniques used by conventional massage and manipulative practitioners. The patient positions on the treatment surface were not extraordinary, given the wide variety of treatment processes used, and indicated the sobadores treat patients in multiple positions. The patient body part contacted by the sobadores indicated that they were treating each of the major parts of the musculoskeletal system. Basic palpation dominated the sobadores' examination methods. The sobadores' primary treatment processes included significant variety, but rubbing was the dominant practice. The hands were the sobador body area that most often made contact with the patient. They all used lubricants. CONCLUSIONS: Sobadores' methods are similar to those of other manual-therapy practitioners. Additional study of video-recorded sobador practices is needed. Video-recorded practice of other traditional and conventional manual therapies for comparative analysis will help delineate the specific similarities and differences among the manual therapies. PMID- 27400121 TI - Three new resin glycosides compounds from Argyreia acuta and their alpha glucosidase inhibitory activity. AB - Three new phenolic compounds, acutacoside C (1), acutacoside D (2) and acutacoside E (3) were isolated from the aerial part of Argyreia acuta. The oligosaccharide chain was composed of two glucoses and three rhamnoses, and the aglycone was (11S)-hydroxyhexadecanoic acid (jalapinolic acid). The core of the three compounds was operculinic acid B, which was rare in resin glycosides. Their structures were established by a combination of spectroscopic and chemical methods. Compounds 1-3 have been evaluated for inhibitory activity against alpha glucosidase, which all showed weak inhibitory activities. PMID- 27400122 TI - The Danger of Not Treating Parkinson Disease Psychosis. PMID- 27400123 TI - Suppressed Polysulfide Crossover in Li-S Batteries through a High-Flux Graphene Oxide Membrane Supported on a Sulfur Cathode. PMID- 27400124 TI - Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis. AB - Progressive tissue fibrosis is a major cause of the morbidity and mortality associated with repeated epithelial injuries and accumulation of myofibroblasts. Successful treatment options are limited by an incomplete understanding of the molecular mechanisms that regulate myofibroblast accumulation. Here, we employed in vivo lineage tracing and real-time gene expression transgenic reporting methods to analyze the early embryonic transcription factor T-box gene 4 (TBX4), and determined that TBX4-lineage mesenchymal progenitors are the predominant source of myofibroblasts in injured adult lung. In a murine model, ablation of TBX4-expressing cells or disruption of TBX4 signaling attenuated lung fibrosis after bleomycin-induced injury. Furthermore, TBX4 regulated hyaluronan synthase 2 production to enable fibroblast invasion of matrix both in murine models and in fibroblasts from patients with severe pulmonary fibrosis. These data identify TBX4 as a mesenchymal transcription factor that drives accumulation of myofibroblasts and the development of lung fibrosis. Targeting TBX4 and downstream factors that regulate fibroblast invasiveness could lead to therapeutic approaches in lung fibrosis. PMID- 27400125 TI - EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis. AB - Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate. PMID- 27400126 TI - Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume. AB - Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis to fine-map this locus to 12 candidate genes. The gene encoding the IL-21 receptor (Il21r) showed a marked difference in strain-specific transcription levels and coding variants in neonatal and adult cortical tissue. Collateral vessel connections were moderately reduced in Il21r-deficient mice, and cerebral infarct volume increased 2.3-fold, suggesting that Il21r modulates both collateral vessel anatomy and innate neuroprotection. In brain slice explants, oxygen deprivation (OD) activated apoptotic pathways and increased neuronal cell death in IL-21 receptor-deficient (IL-21R-deficient) mice compared with control animals. We determined that the neuroprotective effects of IL-21R arose from signaling through JAK/STAT pathways and upregulation of caspase 3. Thus, natural genetic variation in murine Il21r influences neuronal cell viability after ischemia by modulating receptor function and downstream signal transduction. The identification of neuroprotective genes based on naturally occurring allelic variations has the potential to inform the development of drug targets for ischemic stroke treatment. PMID- 27400127 TI - Truncated netrin-1 contributes to pathological vascular permeability in diabetic retinopathy. AB - Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness in the working-age population. Impaired blood-retinal barrier function leads to macular edema that is closely associated with the deterioration of central vision. We previously demonstrated that the neuronal guidance cue netrin-1 activates a program of reparative angiogenesis in microglia within the ischemic retina. Here, we provide evidence in both vitreous humor of diabetic patients and in retina of a murine model of diabetes that netrin-1 is metabolized into a bioactive fragment corresponding to domains VI and V of the full-length molecule. In contrast to the protective effects of full-length netrin-1 on retinal microvasculature, the VI-V fragment promoted vascular permeability through the uncoordinated 5B (UNC5B) receptor. The collagenase matrix metalloprotease 9 (MMP-9), which is increased in patients with diabetic macular edema, was capable of cleaving netrin-1 into the VI-V fragment. Thus, MMP-9 may release netrin-1 fragments from the extracellular matrix and facilitate diffusion. Nonspecific inhibition of collagenases or selective inhibition of MMP 9 decreased pathological vascular permeability in a murine model of diabetic retinal edema. This study reveals that netrin-1 degradation products are capable of modulating vascular permeability, suggesting that these fragments are of potential therapeutic interest for the treatment of DR. PMID- 27400128 TI - ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors. AB - Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1). ApoC-III ASO treatment lowered plasma TGs in mice lacking lipoprotein lipase (LPL), hepatic heparan sulfate proteoglycan (HSPG) receptors, LDLR, or LRP1 and in animals with combined deletion of the genes encoding HSPG receptors and LDLRs or LRP1. However, the ApoC-III ASO did not lower TG levels in mice lacking both LDLR and LRP1. LDLR and LRP1 were also required for ApoC-III ASO-induced reduction of plasma TGs in mice fed a high-fat diet, in postprandial clearance studies, and when ApoC-III-rich or ApoC-III-depleted lipoproteins were injected into mice. ASO reduction of ApoC-III had no effect on VLDL secretion, heparin-induced TG reduction, or uptake of lipids into heart and skeletal muscle. Our data indicate that ApoC-III inhibits turnover of TG-rich lipoproteins primarily through a hepatic clearance mechanism mediated by the LDLR/LRP1 axis. PMID- 27400130 TI - 31 years of lung cancer in the canton of Zurich, Switzerland: incidence trends by sex, histology and laterality. AB - QUESTIONS UNDER STUDY: Lung cancer belongs to the most common cancers in Switzerland. We examined trends in lung cancer incidence, with focus on sex, histology and laterality, in the Canton of Zurich since 1980. MATERIAL AND METHODS: Registry data consisting of 16 798 lung cancer cases from 1980 to 2010 were analysed. Cases were classified into adenocarcinoma (ADC), squamous cell carcinoma (SCC), small-cell carcinoma (SCLC), large cell tumour and carcinoid tumour. Age-standardised (European standard) incidence rates (IR) per 100 000 person-years, male-to-female incidence-rate ratio (M/F-IRR), and left-to-right lung incidence-rate ratio (L/R-IRR) were calculated. RESULTS: Over the study period, ADC occurred most frequently (31.9%), followed by SCC (29.1%), SCLC (15.4%), large cell carcinoma (6.3%), and carcinoid tumour (1.5%). Other/unspecified subtypes accounted for 15.7%. In men, the IR of SCC decreased from 34.2/100 000 (95% confidence interval [CI] 32.5-35.9) in 1980 to 12.8/100 000 (12.0-13.6) in 2010, but increased in women from 3.4/100 000 (2.7-4.0) to 4.0/100 000 (3.4-4.5). The IR of ADC increased in women from 5.1/100 000 (4.1 5.8) to 12.6/100 000 (11.8-13.4) and in men from 15.1/100 000 (14.0-16.3) to 19.4/100 000 (18.4-20.4). Overall M/F-IRR was 2.61; the highest ratio (5.8) was seen for SCC and the lowest (0.77) for carcinoid tumour. All histological subtypes showed a higher susceptibility of the right lung. CONCLUSION: Our data reflect the global increase of lung cancer in women. ADC increased over time in women and men, whereas SCC decreased markedly among men. These trends may have occurred owing to changes in smoking behaviour and cigarette composition. PMID- 27400131 TI - Blood Donor Demographics and Transfusion Recipient Survival-No Country for Old Men? PMID- 27400129 TI - IRF3 promotes adipose inflammation and insulin resistance and represses browning. AB - The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular and secreted factors promote the inflammatory milieu of obesity, but the transcriptional pathways that drive these processes are not well described. Although the canonical inflammatory transcription factor NF-kappaB is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family may also play a role in this process. Here, we determined that IRF3 expression is upregulated in the adipocytes of obese mice and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was associated with reductions in intra-adipose and systemic inflammation in the high fat-fed state, enhanced browning of subcutaneous fat, and increased adipose expression of GLUT4. Taken together, the data indicate that IRF3 is a major transcriptional regulator of adipose inflammation and is involved in maintaining systemic glucose and energy homeostasis. PMID- 27400132 TI - Acceptorless Dehydrogenative Cyclization of o-Aminobenzyl Alcohols with Ketones to Quinolines in Water Catalyzed by Water-Soluble Metal-Ligand Bifunctional Catalyst [Cp*(6,6'-(OH)2bpy)(H2O)][OTf]2. AB - The strategy for acceptorless dehydrogenative cyclization of o-aminobenzyl alcohols with ketones to quinolines in water has been accomplished. In the presence of [Cp*Ir(6,6'-(OH)2bpy)(H2O)][OTf]2, a series of desirable products were obtained in high yields. Notably, this research exhibits the potential for the construction of heterocycles via acceptorless dehydrogenative reactions in water catalyzed by water-soluble metal-ligand bifunctional catalysts. PMID- 27400133 TI - Scripted Nurse Visits: A Resource-Efficient Palliative Care Model for Ventricular Assist Devices. AB - BACKGROUND: The Center for Medicare Services (CMS) requires palliative care involvement for patients who receive a destination therapy ventricular assist device (VAD). Creative solutions are needed to meet this requirement in the context of limited palliative care resources. PURPOSE: To evaluate a novel program in which a nurse conducts scripted pre-VAD visits to promote advance care planning and to triage the need for a full palliative care consult. STUDY DESIGN: Prospective pilot study of patients undergoing evaluation for VAD. METHODS: A script for pre-VAD visits was developed and pilot tested with patients. A registered nurse with basic palliative care training met with patients undergoing evaluation for VAD implantation. Data were collected regarding feasibility and acceptability of the intervention, need for full palliative care consults, and patient outcomes. RESULTS: Between September 2014 and November 2015, the nurse conducted 37 visits. Thirty of the patients subsequently received a VAD. All participants completed the entire nurse visit. Six of the 37 patients required a full palliative care consult during the index hospitalization; these consults were for symptom management, psychosocial distress, or goals of care. Patients were more likely to discuss overarching values than preferences for specific medical interventions. CONCLUSION: Nurses with basic palliative care skills can conduct scripted preparedness planning conversations. These conversations are well received by patients, satisfy CMS requirements, and provide an alternative to full consults for resource-limited programs. Additional research is needed to compare outcomes between nurse visits and traditional consults. PMID- 27400134 TI - Covalent Immobilization of Polyoxotungstate on Alumina and Its Catalytic Generation of Sulfoxides. AB - The structural and chemical stabilities of immobilized polyoxometalate (POM) containing catalysts are crucial factors for their industrial application. An alumina supported POM catalyst is prepared by using a facile condensation reaction between the trilacunary POM Na12 [alpha-P2 W15 O56 ]?24 H2 O (P2 W15 ) and the hydroxy groups on the surface of gamma-Al2 O3 spheres under acidic conditions. The heterogeneous catalyst P2 W15 -Al2 O3 is characterized by a wide variety of techniques and shows excellent stability and highly efficient reactivity and selectivity for the oxygenation of thioethers to sulfoxides, which are a very useful intermediate in organic synthesis and the industrial preparation of drugs. Furthermore, P2 W15 -Al2 O3 can be recycled and reused at least ten times without any observable loss of its catalytic efficiency, mainly due to the covalent immobilization and high dispersion of P2 W15 on the gamma-Al2 O3 surface. PMID- 27400135 TI - Combined application of laryngoscopy and flexible bronchoscopy in endobronchial foreign body extraction. AB - Foreign body aspiration is a life-threatening emergency in children. An 11-year old girl presented at the emergency department with a case of accidental foreign body aspiration. The patient had symptoms of acute respiratory distress followed by cyanosis of the lips. Radiological examination demonstrated a radiopaque foreign body. Under analgesic and amnestic anesthesia, we extracted the metal bead using alligator forceps, with a direct laryngoscope and a flexible bronchoscope. This method afforded an improved visual access to the operative field and allowed for intra-operative manipulation, thus obviating the need for thoracotomy. PMID- 27400137 TI - A Global Analytical Representation of the Potential Energy Surface of the FHF(-) Anion. AB - A global analytical representation of the potential energy hypersurface of the lowest adiabatic electronic state of the FHF(-) anion is derived from ab initio calculations at the coupled cluster level of theory with full single and double and perturbative triple excitations using explicitly correlated atomic basis functions. The new compact function of interatomic distances combines covalent short-range and long-range electrostatic interaction forms and assesses accurately both the lowest reaction channels between the F(-) and HF fragments, with reaction enthalpies to within 1 kJ mol(-1), as well as vibrational terms to within 1.5 cm(-1) deviation from experimental values. PMID- 27400136 TI - Choroidal Watershed Zone and Growth of Polypoidal Choroidal Vasculopathy. AB - PURPOSE: To investigate the topographic relationship between polypoidal choroidal vasculopathy (PCV) growth and choroidal watershed zones (CWZ) by using indocyanine green angiography (ICGA). MATERIALS AND METHODS: We evaluated PCV lesions smaller than the CWZ at baseline and followed up more than 6 months. The CWZ was traced in the early phase ICGA at baseline. The vascular lesion of PCV was traced in baseline and follow-up ICGA. These traces were overlapped and topographic relationships between CWZs and PCV growth were evaluated. RESULTS: Among 31 eyes of 31 patients, enlargement of a PCV lesion was observed in 20 patients (64.5%) at mean follow-up of 30.4 months (6-68 months). A topographical relationship between the CWZ and PCV growth was demonstrated in 14 eyes (70.0%), as the shape of the PCV lesion conformed to the boundary of the CWZ, and/or the growth of the branching vascular network was aligned to the direction of the CWZ extension to the periphery. Growth beyond the boundary of the CWZ was noted in 9 eyes (45.0%), however growth area was greater inside the CWZ than outside in all eyes. Of 15 eyes of extrafoveal lesion at baseline, 8 eyes in which the vascular lesion progressed to the fovea had the CWZ involving the fovea, whereas PCV in three eyes with an extrafoveal CWZ remained as a non-subfoveal disease after mean follow-up of 17.0 months (p = 0.019). CONCLUSIONS: A subfoveal CWZ was related to PCV growth to the fovea. Topographical relationships between PCV growth and the CWZ suggest that choroidal circulation is a predisposition for PCV growth. PMID- 27400138 TI - Ventriculitis from a pituitary prolactinoma: bacterial or chemical? AB - We report the case of a 70-year-old man presenting with pituitary apoplexy from a macroprolactinoma and ventriculitis. It was not possible to distinguish a bacterial or chemical origin, on the basis of his clinical presentation, laboratory studies and imaging, highlighting the importance of prompt imaging and attainment of CSF cultures, in making the diagnosis. PMID- 27400139 TI - Targeting pathways mediating resistance to anti-EGFR therapy in squamous cell carcinoma of the head and neck. AB - INTRODUCTION: As epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of squamous cell carcinomas of the head and neck (SCCHN), several therapeutic agents that target EGFR have been evaluated for the treatment of SCCHN. Although patients with SCCHN derive clinical benefit from anti-EGFR agents, most notably the EGFR monoclonal antibody cetuximab, these patients eventually become resistant to EGFR-based therapies; preclinical studies have shown activation of secondary signaling pathways that lead to resistance to EGFR inhibition and, as such, serve as potential therapeutic targets to overcome resistance to EGFR inhibitors. AREAS COVERED: This review summarizes the results of recently completed trials of anti-EGFR agents in SCCHN, highlights the various mechanisms that drive resistance to EGFR inhibitors in SCCHN, and focuses on several novel targeted agents that could potentially help overcome resistance to EGFR-based therapies in SCCHN. Expert commentary: Due to the development of resistance to EGFR-targeted therapies, novel treatment approaches to overcome resistance are a key unmet need for SCCHN. PMID- 27400140 TI - Nonequimolar Mixture of Organic Acids and Bases: An Exception to the Rule of Thumb for Salt or Cocrystal. AB - Formation of salt and/or cocrystal from organic acid-base mixtures has significant consequences in the pharmaceutical industry and its related intellectual property rights (IPR). On the basis of calculations using periodic dispersion corrected DFT (DFT-D2) on formic acid-pyridine adduct, we have demonstrated that an equimolar stoichiometric ratio (1:1) exists as a neutral cocrystal. On the other hand, the nonequimolar stoichiometry (4:1) readily forms an ionic salt. While the former result is in agreement with the DeltapKa rule between the base and the acid, the latter is not. Calculations reveal that, within the equimolar manifold (n:n; n = 1-4), the mixture exists as a hydrogen bonded complex in a cocrystal-like environment. However, the nonequimolar mixture in a ratio of 5:1 and above readily forms salt-like structures. Because of the cooperative nature of hydrogen bonding, the strength of the O-H...N hydrogen bond increases and eventually transforms into O(-)...H-N(+) (complete proton transfer) as the ratio of formic acid increases and forms salt as experimentally observed. Clearly, an enhanced polarization of formic acid on aggregation increases its acidity and, hence, facilitates its transfer to pyridine. Motion of the proton from formic acid to pyridine is shown to follow a relay mechanism wherein the proton that is far away from pyridine is ionized and is subsequently transferred to pyridine via hopping across the neutral formic acid molecules (Grotthuss type pathway). The dynamic nature of protons in the condensed phase is also evident for cocrystals as the barrier of intramolecular proton migration in formic acid (leading to tautomerism), DeltaH(?)tautomer = 17.1 kcal/mol in the presence of pyridine is half of that in free formic acid (cf. DeltaH(?)tautomer = 34.2 kcal/mol). We show that an acid-base reaction can be altered in the solid state to selectively form a cocrystal or salt depending on the strength and nature of aggregation. PMID- 27400141 TI - Comment on "Case Reports of Two Unusual Donor Site Complications of the Pectoralis Major Myocutaneous Flap and Literature Review" by Beomjune Kim, Arshad Kaleem, and Waleed Zaid. PMID- 27400142 TI - In Reply. PMID- 27400143 TI - Worldwide 10-Year Systematic Review of Treatment Trends in Fibula Free Flap for Mandibular Reconstruction. AB - PURPOSE: The purpose of this study was to describe the trends pertaining to the use of the fibula free flap for mandibular reconstruction during the past 10 years. MATERIALS AND METHODS: A systematic review for publications on the fibula free flap in mandibular reconstruction in the PubMed and Scopus databases was performed from January 1, 2005 until December 31, 2014. Publications were classified by topic, number of patients, and country of origin. The study period was split into 2 periods. The first 5-year period was compared with the second 5 year period. RESULTS: Eighty-five publications were identified. There was an increase in publications regarding restorative decision making (11 vs 9), surgical techniques (13 vs 6), outcomes (20 vs 10), and computer-aided design and computer-aided manufacturing (CAD-CAM; 8 vs 2) in the second 5-year period. The number of patients reported also increased in publications on surgical techniques (1,085 vs 59), outcomes (777 vs 254), bisphosphonate-related osteonecrosis of the jaw and osteoradionecrosis (165 vs 28), and CAD-CAM (65 vs 15) in the second 5 year period. The United States, India, China, and Europe produced most of the publications. CONCLUSIONS: In the past 10 years, there was a surge in publications on the use of the fibula free flap for mandibular reconstruction. There was a 1.8-fold increase in the number of publications and a 3.4-fold increase in the number of patients undergoing this method of mandibular reconstruction in the second 5-year period. Publications from the United States, India, and China contributed to a large increase in the number of patients in the second 5-year period. More interest in CAD-CAM technology was seen in the second 5-year period that was not seen in the first 5-year period. PMID- 27400144 TI - Botulinum Toxin for the Management of Sjogren Syndrome-Associated Recurrent Parotitis. AB - Recurrent parotitis is a rare manifestation of Sjogren syndrome. The management of recurrent parotitis is challenging because conservative methods may be of limited efficacy and invasive approaches carry the risk of complications. Botulinum toxin has been shown to reduce salivary flow, and consequently, the results of its use in the management of recurrent parotitis have been encouraging. A 65-year-old female patient with recurrent parotitis due to Sjogren syndrome was referred to us, complaining of weekly bouts of inflammation. She required a course of antibiotics monthly to control bacterial superinfections. We treated her with onabotulinumtoxinA injections into both parotid glands at regular intervals. After her second injection cycle, she denied further inflammatory bouts, has not required antibiotics in more than 36 months, and denied any side effects. Botulinum toxin may be a safe and effective method of treating Sjogren syndrome-associated recurrent parotitis. PMID- 27400145 TI - Does Combined Spinal Epidural Anesthesia Decrease the Morbidity of Iliac Block Bone Grafting for Deficient Alveolar Ridges Compared With General Anesthesia? AB - PURPOSE: To evaluate the morbidity of iliac block bone grafting performed under general anesthesia (GA) or combined spinal epidural anesthesia (CSEA). MATERIALS AND METHODS: We implemented a retrospective study including patients who underwent anterior iliac block bone grafting for deficient maxillary alveolar ridges. The anesthetic technique (GA or CSEA) was the primary predictor variable. The outcome variables were pain, gait disturbance, neurosensory disturbance (0 to 5 weeks), vomiting tendency (0 to 7 days), and postoperative hospitalization period (0 to 2 days). RESULTS: The sample comprised 22 patients, with 10 in the GA group and 12 in the CSEA group. No surgical complications except sensory disturbance in 2 patients were observed during the study period. Pain during initial healing (P < .001), the gait disturbance rate at 3 weeks after surgery (P = .003), and the vomiting tendency on the day of surgery (P < .001) were significantly higher in the GA group than in the CSEA group; all variables showed significant improvement with time in both groups. The postoperative hospitalization period was also significantly longer for the GA group than for the CSEA group (P < .001). No significant difference was observed between groups with regard to neurosensory disturbance. CONCLUSIONS: Iliac block bone grafting for deficient maxillary ridges can be successful under both GA and CSEA, although CSEA results in less pain and vomiting and early recovery, thus increasing patient comfort. PMID- 27400147 TI - Low Concentration of Salmonella enterica and Generic Escherichia coli in Farm Ponds and Irrigation Distribution Systems Used for Mixed Produce Production in Southern Georgia. AB - Studies have shown that irrigation water can be a vector for pathogenic bacteria. Due to this, the Food Safety Modernization Act's (FSMA) produce safety rule requires that agricultural water directly applied to produce be safe and of adequate sanitary quality for use, which may pose a challenge for some farmers. The purpose of this research was to assess the presence and concentration of Salmonella and generic Escherichia coli in irrigation water from distribution systems in a mixed produce production region of southern Georgia. Water samples were collected during three growing seasons at three farms irrigating crops with surface water (Pond 1, Pond 2) or groundwater (Well) during 2012-2013. Salmonella and generic E. coli populations were monitored by culture and Most Probable Number (MPN). Confirmed isolates were characterized by pulsed-field gel electrophoresis and serotyping. In Pond 1, Salmonella was detected in 2/21 surface, 5/26 subsurface, 10/50 center pivot, and 0/16 solid set sprinkler head water samples. In Pond 2, Salmonella was detected in 2/18 surface, 1/18 subsurface, 6/36 drip line start, and 8/36 drip line end water samples. Twenty six well pumps and 64 associated drip line water samples were negative. The overall mean Salmonella concentration for positive water samples was 0.03 MPN/100 mL (range <0.0011-1.8 MPN/100 mL). Nine Salmonella serovars comprising 22 pulsotypes were identified. Identical serovars and subtypes were found three times on the same day and location: Pond 1-Pivot-Cantaloupe (serovar Rubislaw), Pond 1-Pivot-Peanut (serovar Saintpaul), and Pond 2-Drip Line Start-Drip Line End Yellow Squash (serovar III_16z10:e,n,x,z15). Generic E. coli was detected in water from both farm ponds and irrigation distribution systems, but the concentrations met FSMA microbial water quality criteria. The results from this study will allow producers in southern Georgia to better understand how potential pathogens move through irrigation distribution systems. PMID- 27400146 TI - Stochastic alternative splicing is prevalent in mungbean (Vigna radiata). AB - Alternative splicing (AS) can produce multiple mature mRNAs from the same primary transcript, thereby generating diverse proteins and phenotypes from the same gene. To assess the prevalence of AS in mungbean (Vigna radiata), we analysed whole-genome RNA sequencing data from root, leaf, flower and pod tissues and found that at least 37.9% of mungbean genes are subjected to AS. The number of AS transcripts exhibited a strong correlation with exon number and thus resembled a uniform probabilistic event rather than a specific regulatory function. The proportion of frameshift splicing was close to the expected frequency of random splicing. However, alternative donor and acceptor AS events tended to occur at multiples of three nucleotides (i.e. the codon length) from the main splice site. Genes with high exon number and expression level, which should have the most AS if splicing is purely stochastic, exhibited less AS, implying the existence of negative selection against excessive random AS. Functional AS is probably rare: a large proportion of AS isoforms exist at very low copy per cell on average or are expressed at much lower levels than default transcripts. Conserved AS was only detected in 629 genes (2.8% of all genes in the genome) when compared to Vigna angularis, and in 16 genes in more distant species like soya bean. These observations highlight the challenges of finding and cataloguing candidates for experimentally proven AS isoforms in a crop genome. PMID- 27400148 TI - Tumor-induced stromal reprogramming drives lymph node transformation. AB - Lymph node (LN) stromal cells, particularly fibroblastic reticular cells (FRCs), provide critical structural support and regulate immunity, tolerance and the transport properties of LNs. For many tumors, metastasis to the LNs is predictive of poor prognosis. However, the stromal contribution to the evolving microenvironment of tumor-draining LNs (TDLNs) remains poorly understood. Here we found that FRCs specifically of TDLNs proliferated in response to tumor-derived cues and that the network they formed was remodeled. Comparative transcriptional analysis of FRCs from non-draining LNs and TDLNs demonstrated reprogramming of key pathways, including matrix remodeling, chemokine and/or cytokine signaling, and immunological functions such as the recruitment, migration and activation of leukocytes. In particular, downregulation of the expression of FRC-derived chemokine CCL21 and cytokine IL-7 were accompanied by altered composition and aberrant localization of immune-cell populations. Our data indicate that following exposure to tumor-derived factors, the stroma of TDLNs adapts on multiple levels to exhibit features typically associated with immunosuppression. PMID- 27400150 TI - The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory. AB - Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity. PMID- 27400149 TI - WNK1 kinase balances T cell adhesion versus migration in vivo. AB - Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1 deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration. PMID- 27400151 TI - Deglutition and respiratory patterns during sleep in the aged. AB - CONCLUSION: Deglutition was extremely infrequent and displayed unique patterns during sleep in the aged. OBJECTIVES: The deglutition and respiratory phase patterns during sleep in the healthy aged were investigated in this study. METHODS: Ten aged adults (average age = 71 years) were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid muscles) related to swallowing. RESULTS: During sleep, swallowing was extremely infrequent and absent for long periods in the aged. The median number of swallows per hour during total sleep time was 0.6, and the median longest deglutition-free period was 134.8 minutes. Most deglutition occurred in association with spontaneous electroencephalographic arousal both in REM and non-REM sleep. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the mean deglutition frequency. There was no deglutition during deep sleep. Overall muscle tone is inhibited during REM sleep. However, deglutition also occurred in association with spontaneous EEG arousal. The deeper the sleep stage, the lower the mean arousal frequency, and the lower the mean ratio of arousal with deglutition to arousal. Approximately one-third of swallows occurred after inspiration and were followed by inspiration. PMID- 27400152 TI - Deciphering the biology of deltasatellites from the New World: maintenance by New World begomoviruses and whitefly transmission. AB - Deltasatellites are small noncoding DNA satellites associated with begomoviruses. The study presented here has investigated the biology of two deltasatellites found in wild malvaceous plants in the New World (NW). Infectious clones of two NW deltasatellites (from Malvastrum coromandelianum and Sidastrum micranthum) and associated begomoviruses were constructed. Infectivity in Nicotiana benthamiana and their natural malvaceous hosts was assessed. The NW deltasatellites were not able to spread autonomously in planta, whereas they were maintained by the associated bipartite begomovirus. Furthermore, NW deltasatellites were transreplicated by a monopartite NW begomovirus, tomato leaf deformation virus. However, they were not maintained by begomoviruses from the Old World (tomato yellow leaf curl virus, tomato yellow leaf curl Sardinia virus and African cassava mosaic virus) or a curtovirus (beet curly top virus). NW deltasatellites did not affect the symptoms induced by the helper viruses but in some cases reduced their accumulation. Moreover, one NW deltasatellite was shown to be transmitted by the whitefly Bemisia tabaci, the vector of its helper begomoviruses. These results confirm that these molecules are true satellites. The availability of infectious clones and the observation that NW deltasatellites reduced virus accumulation paves the way for further studies of the effect on their helper begomoviruses. PMID- 27400153 TI - Fast magic-angle sample spinning solid-state NMR at 60-100kHz for natural abundance samples. AB - In spite of tremendous progress made in pulse sequence designs and sophisticated hardware developments, methods to improve sensitivity and resolution in solid state NMR (ssNMR) are still emerging. The rate at which sample is spun at magic angle determines the extent to which sensitivity and resolution of NMR spectra are improved. To this end, the prime objective of this article is to give a comprehensive theoretical and experimental framework of fast magic angle spinning (MAS) technique. The engineering design of fast MAS rotors based on spinning rate, sample volume, and sensitivity is presented in detail. Besides, the benefits of fast MAS citing the recent progress in methodology, especially for natural abundance samples are also highlighted. The effect of the MAS rate on (1)H resolution, which is a key to the success of the (1)H inverse detection methods, is described by a simple mathematical factor named as the homogeneity factor k. A comparison between various (1)H inverse detection methods is also presented. Moreover, methods to reduce the number of spinning sidebands (SSBs) for the systems with huge anisotropies in combination with (1)H inverse detection at fast MAS are discussed. PMID- 27400154 TI - Journal editors and their h-index. PMID- 27400155 TI - Mobility and Reactivity of Oxygen Adspecies on Platinum Surface. AB - The adsorption and mobility of oxygen adspecies on platinum (Pt) surface are crucial for the oxidation of surface-absorbed carbon monoxide (CO), which causes the deactivation of Pt catalyst in fuel cells. By employing nanoelectrode and ultramicroelectrode techniques, we have observed the surface mobility of oxygen adspecies produced by the dissociative adsorption of H2O and the surface reaction between the oxygen adspecies and the preadsorbed CO on the Pt surface. The desorption charge of oxygen adspecies on a Pt nanoelectrode has been found to be in proportion to the reciprocal of the square root of scan rate. Using this information, the apparent surface diffusion coefficient of oxygen adspecies has been determined to be (5.61 +/- 0.84) * 10(-10) cm(2)/s at 25 degrees C. During the surface oxidation of CO, two current peaks are observed, which are attributed to CO oxidation at the Pt/electrolyte interface and the surface mobility of the oxygen adspecies on the adjacent Pt surface, respectively. These results demonstrate that the surface mobility of oxygen adspecies plays an important role in the antipoisoning and reactivation of Pt catalyst. PMID- 27400156 TI - US Health Care Reform: Cost Containment and Improvement in Quality. PMID- 27400157 TI - Racial Disparities in the Outcomes of Patients With Stage IV Pancreatic Adenocarcinoma Are Mediated by Chemotherapy Utilization. PMID- 27400158 TI - Reply. PMID- 27400159 TI - Pancreatic Cancer and Osteopontin: The Relationship Remains Unclear. PMID- 27400160 TI - The Final Cytopathologic Diagnosis of Initially "Indeterminate" Pancreatic Mass Lesions. PMID- 27400161 TI - Tyrosine Phosphorylation of Focal Adhesion Anchoring Proteins Enhances Human Pancreatic Cancer Cell Invasion. PMID- 27400162 TI - A Cross-sectional Study to Assess the Prevalence of Pancreatic Exocrine Insufficiency Among Diabetes Mellitus Patients in Turkey. PMID- 27400163 TI - Investigation of Coulombic bremsstrahlung spectra of metallic targets for the photon energy region of 1-100keV. AB - In the present paper, the formation of bremsstrahlung spectra by ordinary bremsstrahlung (OB) and polarization bremsstrahlung (PB) in metallic targets by (35)S beta particles has been investigated in the photon energy region of 1 100keV. From the experimental measurements and the theoretical results obtained from Elwert corrected (non-relativistic) Bethe Heitler (EBH) theory, modified Elwert factor (relativistic) (FmodBH) theories for OB and Avdonina and Pratt (FmodBH+PB) theory for total bremsstrahlung (BS) having the contribution of PB into OB, it has been found that the contribution of PB into BS in a target is limited to a low energy region only and also varies with the atomic number of target material. The FmodBH+PB theory is in agreement with the experimental results in low energy regions of the target, whereas at high energy region FmodBH is found to give better agreement. Further, the present experimental results indicate that the screening effects in the Coulombic bremsstrahlung process cannot be neglected in the high energy region, and the multiple scattering and secondary electron emissions effects in thick target are required to be taken into account in describing the bremsstrahlung process. PMID- 27400165 TI - From the Editor. PMID- 27400164 TI - Influence of Silver-hydroxyapatite Nanocomposite Coating on Biofilm Formation of Joint Prosthesis and Its Mechanism. AB - Background: The main reason for biomaterial related refractory infections is biofilm formation caused by bacterial adhesion on the surface of materials. Silver-hydroxyapatite (Ag/HA) nanocomposite coating can inhibit the formation of biofilm, but its mechanism is not clear. Material and method: In order to clarify the mechanism, the amounts of biofilm on the Ag/HA composite coating and HA coating were determined, the release rates of silver nanoparticles in simulated body fluid (SBF) were detected by atomic absorption spectrometry, and the expression values of atlE, fbe, sap, iapB genes of Staphylococcus aureus were studied when they grew on Ag/HA composite coating and HA coating. Results: The amount of the biofilm on the Ag/HA composite coating was significantly less than that on the HA coating, and the bacterial adhesion was decreased. The silver nanoparticles were released continuously in SBF and the release rate decreased gradually with time. The expression values of atlE, fbe and sap were high in the initial stage of adhesion and the expression value of iapB was high in the colonies-gathering stage in the control group, but they were all significantly inhibited in the presence of Ag. Conclusion: These results indicated that the main antibacterial effect of Ag/HA composite coating was achieved by the release of silver nanoparticles. The addition of Ag inhibited the expression of genes related to biofilm formation, which in turn inhibited the formation of biofilms. This provided theoretical support for the clinical application of Ag/HA composite coating. PMID- 27400166 TI - A Case of Genital Self-Mutilation in a Female-Symptom Choice and Meaning. AB - Self-mutilation is understood as any willful gesture or alteration of the body tissue without a suicidal intent. The most common self-mutilating gestures are, to a great extent, those that are superficial or moderate, such as cuts, burns, or bites. The most severe, as is the case of genital self-mutilation (GSM), are extremely rare and, in most cases, observed in patients suffering from psychosis. Furthermore, they are mostly reported from a surgical standpoint. Here, we report the case of a 20-year-old female patient who resorted to the emergency department after having amputated her clitoris with surgical scissors. This dramatic gesture, coupled with the patient's narrative, prompted for differential diagnosis between a psychotic syndrome and a severe personality disorder. We propose that, despite the magnitude of the self-harm, it is possible to conceptualize this GSM within a disturbed personality with significant sexuality issues and, therefore, this case report aims to broaden the limits that have been associated with the self-mutilating gestures in borderline personality disorder. PMID- 27400167 TI - Re:Urethral bulking for recurrent stress urinary incontinence after midurethral sling failure. AB - The Integral Theory consists of nine specific sites three main compartments which are supporting the female pelvis. Stress urinary incontinence (SUI) is caused due to laxity in the vaginal supporting ligaments in especially anterior pelvic compartment which consists of pubourethral ligament, external urethral ligament, and hammock. The diagnose of each failure should be distinguished for the choose of the most effective treatment. Neurourol. Urodynam. 36:1218-1218, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27400168 TI - Near-Infrared Luminescence and Inner Filter Effects of Lanthanide Coordination Polymers with 1,2-Di(4-pyridyl)ethylene. PMID- 27400169 TI - Leading with a vision for the future. PMID- 27400170 TI - The varied and expanding role of risk management practice. PMID- 27400171 TI - Scorecard implementation improves identification of postpartum patients at risk for venous thromboembolism. AB - OBJECTIVE: To evaluate if an intensive educational intervention in the use of a standardized venous thromboembolism (VTE) risk assessment tool (scorecard) improves physicians' identification and chemoprophylaxis of postpartum patients at risk for VTE. METHODS: After implementation of a VTE scorecard and prior to an intensive educational intervention, postpartum patients (n = 140) were evaluated to assess scorecard completion, risk factors, and chemoprophylaxis. A performance improvement campaign focusing on patient safety, VTE prevention, and scorecard utilization was then conducted. Evaluation of the same parameters was subsequently performed for a similar group of patients (n = 133). Differences in scorecard utilization and risk assessment were tested for statistical significance. RESULTS: Population-at-risk rates were similar in both assessment periods (31.4% vs 28.6%; p = NS). The greatest risk factors included cesarean delivery, body mass index (BMI) >30 and age >35. Scorecard completion rates for all patients increased in the postintervention period (15.7% vs 67.7%; p < .001). Postintervention scorecard completion rates for the at-risk population also improved (20% vs 79%; p < .001). In the postintervention group, those at risk with completed scorecards had higher prophylaxis rates than those at risk without scorecards (73% vs 25%; p = .03). At-risk patients with completed scorecards had 2.6 times more orders for chemoprophylaxis than at-risk patients without scorecards in both time periods (odds ratio [OR] = 8.4; 95% confidence interval [CI] 3.1-22.8). CONCLUSION: Utilization of a VTE scorecard coupled with an educational intervention for health care providers increases detection and chemoprophylaxis orders for at-risk patients. Encouraging universal scorecard assessment standardizes identification and chemoprophylaxis of at-risk patients who were otherwise not perceived to be at risk. PMID- 27400172 TI - When it comes to securing patient health information from breaches, your best medicine is a dose of prevention: A cybersecurity risk assessment checklist. AB - BACKGROUND: Health care stakeholders are concerned about the growing risk of protecting sensitive patient health information from breaches. The Federal Emergency Management Agency (FEMA) has identified cyber attacks as an emerging concern, and regulations such as the Health Insurance Portability and Accountability Act (HIPAA) and the Health Information Technology for Economic and Clinical Health Act (HITECH) have increased security requirements and are enforcing compliance through stiff financial penalties. PURPOSES: The purpose of this study is to describe health care breaches of protected information, analyze the hazards and vulnerabilities of reported breach cases, and prescribe best practices of managing risk through security controls and countermeasures. Prescriptive findings were used to construct a checklist tool to assess and monitor common risks. METHODOLOGY: This research uses a case methodology to describe specific examples of the 3 major types of cyber breach hazards: portable device, insider, and physical breaches. We utilize a risk management framework to prescribe preventative actions that organizations can take to assess, analyze, and mitigate these risks. FINDINGS: The health care sector has the largest number of reported breaches, with 3 major types: portable device, insider, and physical breaches. Analysis of actual cases indicates security gaps requiring prescriptive fixes based on "best practices." PRACTICE IMPLICATIONS: Our research culminates in a 25-item checklist that organizations can use to assess existing practices and identify security gaps requiring improvement. PMID- 27400173 TI - Vicarious liability: Is it an issue for your organization? AB - Vicarious liability is a very real concern for hospitals and other health care entities. There are two forms of vicarious liability: respondeat superior (liability for an employee's actions) and agency (liability for nonemployees who appear to be the agent of the entity). Since an entity works through its employees, there is little that can be done, in most cases, to avoid respondeat superior liability. Entities need to be aware of the ways in which nonemployees can be perceived to be the entity's agent so that the appearance of agency can be prevented. There are methods to avoid vicarious liability and to deal with it should it occur. PMID- 27400174 TI - TeamSTEPPS for health care risk managers: Improving teamwork and communication. AB - BACKGROUND: Ineffective communication among the health care team is a leading cause of errors in the patient care setting. Studies assessing training related to communication and teamwork in the clinical team are prevalent, however, teamwork training at the administrative level is lacking. This includes individuals in leadership positions such as health care risk managers. PURPOSE: The purpose was to determine the impact of an educational intervention on the knowledge and attitudes related to communication and teamwork in the health care risk management population. METHODS: The educational intervention was an adaptation of a national teamwork training program and incorporated didactic content as well as video vignettes and small group activities. Measurement of knowledge and attitudes were used to determine the impact of the education program. Knowledge and attitudes were assessed pre- and postcourse. RESULTS: Findings indicate that teamwork education tailored to the needs of the specific audience resulted in knowledge gained and improved attitudes toward the components of teamwork. The attitudes that most significantly improved were related to team structure and situation monitoring. There was no improvement in participants' attitudes toward leadership, mutual support, and communication. CONCLUSION: Team training has been shown to improve safety culture, patient satisfaction, and clinical outcomes. Including risk managers in training on teamwork, communication, and collaboration can serve to foster a common language among clinicians and management. In addition, a measurement related to implementation in the health care setting may yield insight into the impact of training. Qualitative measurement may allow the researcher to delve deeper into how these health care facilities are using team training interventions. PMID- 27400175 TI - Case law update. PMID- 27400176 TI - A B-type histone acetyltransferase Hat1 regulates secondary metabolism, conidiation, and cell wall integrity in the taxol-producing fungus Pestalotiopsis microspora. AB - In filamentous fungi, many gene clusters for the biosynthesis of secondary metabolites often stay silent under laboratory culture conditions because of the absence of communication with its natural environment. Epigenetic processes have been demonstrated to be critical in the expression of the genes or gene clusters. Here, we report the identification of a B-type histone acetyltransferase, Hat1, and demonstrate its significant roles in secondary metabolism, conidiation, and the cell wall integrity in the fungus Pestalotiopsis microspora. An hat1 deletion strain shows a dramatic decrease of SMs in this fungus, suggesting hat1 functions as a global regulator on secondary metabolism. Moreover, the mutant strain hat1Delta delays to produce conidia with significantly decreased number of conidia, while shows little effect on vegetative growth, suggesting that it plays a critical role in conidiation. The hypersensitivity of hat1Delta to Congo red demonstrates that disruption of hat1 impairs the integrity of cell wall. Overexpression of the wild-type hat1 allele enhances conidiation by boosting the number of conidia. This is the first report on the role of a B-type histone acetyltransferase in fungal secondary metabolism and cell wall integrity. PMID- 27400177 TI - Patient participation: are we far from fulfilling the vision of patient-centred care? PMID- 27400178 TI - Plant-Based Diets: A Physician's Guide. AB - Because of the ever-increasing body of evidence in support of the health advantages of plant-based nutrition, there is a need for guidance on implementing its practice. This article provides physicians and other health care practitioners an overview of the myriad benefits of a plant-based diet as well as details on how best to achieve a well-balanced, nutrient-dense meal plan. It also defines notable nutrient sources, describes how to get started, and offers suggestions on how health care practitioners can encourage their patients to achieve goals, adhere to the plan, and experience success. PMID- 27400179 TI - Image Diagnosis: Encephalopathy Resulting from Dural Arteriovenous Fistula. PMID- 27400180 TI - Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives. AB - INTRODUCTION: Little is known about the attitudes of faculty and residents toward the use of patient experience data as a tool for providing resident feedback. The purpose of this study was to explore the attitudes of teaching faculty surrounding patient experience data and how those attitudes may influence the feedback given to trainees. METHODS: From July 2013 to August 2013, we conducted in-depth, face-to-face, semistructured interviews with 9 attending physicians who precept residents in internal medicine at 2 continuity clinics (75% of eligible attendings). Interviews were coded using conventional content analysis. RESULTS: Content analysis identified six potential barriers in using patient experience survey data to provide feedback to residents: 1) perceived inability of residents to learn or to incorporate feedback, 2) punitive nature of feedback, 3) lack of training in the delivery of actionable feedback, 4) lack of timeliness in the delivery of feedback, 5) unclear benefit of patient experience survey data as a tool for providing resident feedback, and 6) lack of individualized feedback. CONCLUSION: Programs may want to conduct an internal review on how patient experience data is incorporated into the resident feedback process and how, if at all, their faculty are trained to provide such feedback. PMID- 27400181 TI - Side chain variations radically alter the diffusion of poly(2-alkyl-2-oxazoline) functionalised nanoparticles through a mucosal barrier. AB - Functionalised nanomaterials are gaining popularity for use as drug delivery vehicles and, in particular, mucus penetrating nanoparticles may improve drug bioavailability via the oral route. To date, few polymers have been investigated for their muco-penetration, and the effects of systematic structural changes to polymer architectures on the penetration and diffusion of functionalised nanomaterials through mucosal tissue have not been reported. We investigated the influence of poly(2-oxazoline) alkyl side chain length on nanoparticle diffusion; poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), and poly(2-n-propyl-2 oxazoline) were grafted onto the surface of thiolated silica nanoparticles and characterised by FT-IR, Raman and NMR spectroscopy, thermogravimetric analysis, and small angle neutron scattering. Diffusion coefficients were determined in water and in a mucin dispersion (using Nanoparticle Tracking Analysis), and penetration through a mucosal barrier was assessed using an ex vivo fluorescence technique. The addition of a single methylene group in the side chain significantly altered the penetration and diffusion of the materials in both mucin dispersions and mucosal tissue. Nanoparticles functionalised with poly(2 methyl-2-oxazoline) were significantly more diffusive than particles with poly(2 ethyl-2-oxazoline) while particles with poly(2-n-propyl-2-oxazoline) showed no significant increase compared to the unfunctionalised particles. These data show that variations in the polymer structure can radically alter their diffusive properties with clear implications for the future design of mucus penetrating systems. PMID- 27400182 TI - Synthesis of Ocotillol-Type Ginsenosides. AB - A total of 14 ocotillol-type ginsenosides were conveniently synthesized employing glycosylation of ocotillol sapogenin derivatives with glucosyl ortho alkynylbenzoate donors under the promotion of a gold(I) catalyst as the key step. Relying on a rational protecting group strategy and the unexpected regioselectivity of the glycosylation of the 3,25-diol sapogenins (2a/2b, 5a/5b) for the tertiary 25-OH, mono 3-O-glucosyl ocotillol-PPD, 6-O-glucosyl ocotillol PPT, 25-O-glucosyl ocotillol-PPD/PPT and 3,25-di-O-glucosyl ocotillol-PPD/PPT ginsenosides were prepared in which the configuration at the C-24 is either R or S. PMID- 27400183 TI - Cost-effectiveness modelling of novel oral anticoagulants incorporating real world elderly patients with atrial fibrillation. AB - BACKGROUND: Novel oral anticoagulants (NOACs) expand the treatment options for patients with atrial fibrillation (AF). Their benefits need to be weighed against the risk-benefit ratio in real-world elderly patients, prompting this cost effectiveness study of NOACs (apixaban, dabigatran, edoxaban and rivaroxaban), warfarin and aspirin for stroke prevention in AF. METHODS: Applying effectiveness estimates from a network meta-analysis involving over 800,000 patients from randomised controlled trials and observation studies, our Markov model projected cost and health outcomes for a cohort of 65-year-old AF patients over a life time. We performed subgroup analysis stratified by age (65-74 and >=75years), with further analysis limited to observational studies involving dabigatran and rivaroxaban. RESULTS: Compared to warfarin, NOACs (except dabigatran 110) were associated with incremental cost-effectiveness ratios ranging from USD 24,476 to USD 41,448 that were within cost-effectiveness threshold of USD 49,700 (one gross domestic product per capita in Singapore in 2015). Aspirin regimens were dominated. In elderly aged >=75years, cost effectiveness of NOACs (except apixaban) decreased, owing to worsened performance in safety profile. Analysis limited to observational studies revealed that dabigatran 150 and rivaroxaban were not cost-effective, reflecting increased bleeding risks in non-controlled settings. Threshold analyses revealed that apixaban was no longer cost-effective at two to three times higher bleeding risk. CONCLUSIONS: Whilst NOACs are cost effective in the younger elderly compared to warfarin, their benefits appear to be offset by worsened risk profile in older elderly, especially in non-controlled settings. Decisions on appropriate AF treatment should balance treatment-related benefits, risks, and patient preference. PMID- 27400184 TI - Heart failure hospitalization: An important prognostic factor for heart failure re-admission and mortality. AB - BACKGROUND: Few studies have evaluated incidence rates and risk factors for heart failure hospitalization (HFH) and mortality starting at initial heart failure (HF) diagnosis. METHODS: Patients with a first ever recorded diagnosis of HF between January 2000 and December 2005 (N=3516) were identified from The Health Improvement Network primary care database and followed until April 2011 to identify HFHs (through linked hospitalization data) and deaths. HF patients were stratified by hospitalization status at HF diagnosis (start date), and hazard ratios (HRs) for HFH and death were estimated using Cox regression. Predictors of HF re-admission were identified by nested case-control analysis among patients hospitalized at start date, using patients with a new HFH during follow-up as cases and a set of age and sex matched controls. RESULTS: During a mean follow-up of 4.5years, 32% of incident HF patients (n=1119) had a HFH and 58.5% died (n=2056). Compared with patients not hospitalized at initial HF diagnosis (N=2759), a two-fold increased risk of HFH during follow-up, consistent over time, was seen in patients hospitalized at initial HF diagnosis (N=757); adjusted HR 2.14 (95% CI: (1.88-2.44). Major predictors of HFH were renal impairment, diabetes and prior HFH. Mortality rates were higher in HF patients hospitalized at initial HF diagnosis, but the major determinant of mortality was HFH during follow-up: HR 3.88 (95% CI: 3.53-4.26) irrespective of HFH status at initial diagnosis. CONCLUSION: Patients hospitalized at initial HF diagnosis or with a HFH thereafter are at high risk of worse outcomes. PMID- 27400186 TI - Novel three dimensional myocardial strain parameter thresholds on resting transthoracic echocardiography for detection of left ventricular ischemic segments determined by invasive fractional flow reserve. PMID- 27400185 TI - Mean platelet volume and mortality risk in a national incident hemodialysis cohort. AB - BACKGROUND: Higher mean platelet volume (MPV) is an indicator of larger, reactive platelets, and has been associated with a higher risk of thrombosis and cardiovascular events in the general population. Hemodialysis patients have a higher risk for cardiovascular death and predisposition to platelet dysfunction (thrombosis and bleeding diathesis), but the relationship between MPV and mortality in this population is unknown. METHODS: Among a 5-year cohort (1/2007 12/2011) of 149,118 incident hemodialysis patients from a large national dialysis organization, we examined the association between MPV and all-cause mortality. In primary analyses, we granularly analyzed MPV across five categories: 7.2-7.5, >7.5-9.5, >9.5-11.5, >11.5-13.5, and >13.5-15.0fL. In secondary analyses, we examined MPV categorized as low, normal, and high based on thresholds in the general population: 7.2-7.5, >7.5-11.5, and >11.5fL, respectively. Associations between baseline and time-dependent MPV with mortality were estimated using traditional and time-dependent Cox models in order to determine long-term and short-term exposure-mortality associations, respectively, using three adjustment levels: unadjusted, case-mix, and case-mix+laboratory models. RESULTS: In primary analyses, higher baseline and time-dependent MPV levels were associated with incrementally higher death risk in case-mix+laboratory analyses (reference: >9.5 11.5fL). In secondary analyses, high baseline and time-dependent MPV levels were associated with higher mortality, whereas low MPV was associated with lower death risk across all multivariable models (reference: normal MPV). CONCLUSIONS: Hemodialysis patients with higher MPV have heightened mortality risk. Further studies are needed to determine the pathophysiologic basis for the higher risk, and if modification of MPV ameliorates mortality in this population. PMID- 27400187 TI - Circumferential ablation at the base of the left ventricular papillary muscles: A highly effective approach for ventricular arrhythmias originating from the papillary muscles. AB - BACKGROUND: Radiofrequency catheter ablation (RFCA) of ventricular arrhythmias (VAs) originating from the left ventricular (LV) papillary muscles (PMs) is challenging. METHODS: We enrolled 16 consecutive patients who received RFCA for VAs from LV PMs. Three-dimensional electroanatomical mapping was used to construct activation and/or pace maps. RFCA was performed first at the earliest activation site or at the best matched site in the pace maps. When an acceleration or reduction in the incidence of VAs was observed during the first few seconds of the application, the ablation energy was delivered continuously for 60-120s. Additional ablation was then circumferentially delivered at the base of the PMs. RESULTS: RFCA was successfully performed in all 16 patients with no cases of recurrence of VAs after a mean follow-up of 20+/-12months. VAs originated from the anterior (n=8) and posterior (n=8) PMs. Purkinje potentials were identified at the target sites in seven patients. All VAs were temporarily suppressed by one to two long-duration shots of RFCA at the initial targeted site, but recurrence was subsequently noted. In six patients, the QRS morphologies of the VAs changed after the initial RFCA. A subsequent circumferential approach with multiple ablations applied to the base of the PMs completely eliminated all VAs. In all but one patient, successful RFCA was achieved using an open-irrigated ablation catheter. CONCLUSIONS: Circumferential RFCA at the base of the PMs overcame anatomical limitations, leading to a high success rate of RFCA for VAs from LV PMs. PMID- 27400188 TI - Is BMI accurate to reflect true adiposity? PMID- 27400189 TI - Comparing different calcification scores to detect outcomes in chronic kidney disease patients with vascular calcification. AB - BACKGROUND: There is no consensus on the most appropriate technique to diagnose vascular calcification in chronic kidney disease. This is primarily because of the absence of direct comparisons of predictive values of the various calcification scores, especially outside the coronary vascular beds, to detect clinical outcomes. METHODS: We included 93 haemodialysis patients and performed 6 vascular calcification scores: two scores utilised simple X-rays of abdominal aorta and peripheral vessels. CT scans of the thoracic, upper abdominal and lower abdominal aorta were performed to calculate the aortic calcification index and CT of the pelvis for calcification of iliac vessels. Patients were followed for 63months (mean 46.8months) for first major cardiovascular events and mortality. RESULTS: Nineteen cardiovascular events and 28 deaths occurred. Calcification was detected more sensitively in central and peripheral beds using CT scans compared to X-rays (p<0.001). CT scans detected calcification more frequently in distal than proximal vascular beds (p<0.001). Calcification of the pelvic vessels and lower abdominal aorta were most predictive of events including pre-existing cardiovascular disease O.R. 6.5 (95% C.I. 2-22; p=0.001) and O.R. 3 (95% C.I. 1.1 9; p=0.035); new major cardiovascular events H.R. 4.2 (95% C.I. 1.5-11; p=0.006) and H.R. 2 (95% C.I. 0.8-5.3; p=0.1) as well as mortality H.R. 2.8 (95% C.I. 1.3 6; p=0.01) and H.R. 2.2 (95% C.I. 1.04-5; p=0.04) respectively. CONCLUSIONS: CT based techniques are more sensitive than plain X-rays at detecting peripheral and aortic vascular calcifications. Distal CT scans of the aorta and pelvic vessels have the highest predictive value for cardiovascular events and mortality. PMID- 27400190 TI - What is the association of lipid levels and incident stroke? AB - BACKGROUND: The association between lipid levels and stroke rates is less than lipid levels and coronary heart disease (CHD). OBJECTIVE: To assess if there are geographic, racial, and ethnic differences in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels with incident stroke. METHODS: From the REasons for Geographic And Racial Differences in Stroke (REGARDS) study we evaluated baseline levels of LDL-C, HCL-C, TC, Non-HDL-C (Total-HDL-C) and triglycerides in participants free of prevalent stroke at baseline. Cox Proportional-Hazard models were the main analytical tool used to examine the association between incident stroke and lipids. For each adjusted lipid measure (LDL-C, HDL-C, triglycerides, TC, and non-HDL-C) we calculated a series of incremental models. RESULTS: The analysis cohort was 23,867 participants with a mean follow-up time of 7.5+/ 2.9years, and 1031 centrally adjudicated strokes (874 ischemic and 77 hemorrhagic strokes). HDL-C baseline level was associated with an overall unadjusted 13% risk reduction (HR 0.87, 95% confidence interval [CI]: 0.81-0.93; p<0.05; 14% for ischemic and 16% for hemorrhagic strokes), and TC with an 8% (HR 0.92, 95%CI: 0.87-0.99; p<0.05) risk reduction of all strokes. When the results were fully adjusted a significant association was observed only for LDL-C and non-HDL-C and ischemic stroke. There were no significant differences in these associations when adjusted for age, race, age*race, gender, education, region, or income. CONCLUSION: In a disease free population, LDL-C and non-HDL-C baseline levels are significantly associated with the risk of ischemic stroke. PMID- 27400191 TI - Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: Meta-analysis of randomized controlled trials. AB - OBJECTIVE: After implantation of drug-eluting stents (DES), patients usually receive 6-12months of dual antiplatelet therapy (DAPT). However, the optimal duration of DAPT is controversial. Therefore, we performed a meta-analysis of randomized controlled trials to assess the risks and benefits of different DAPT durations. METHODS: We searched the literature using MEDLINE, Scopus, EMBASE, ISI Web of Science, Cochrane Library, ClinicalTrials.gov and recent conference proceedings, and included those trials randomizing patients to receive different durations of DAPT after DES implantation and reporting frequencies of cardiovascular and bleeding events. Data from eleven trials were analyzed using RevMan. RESULTS: Compared to 12-month DAPT treatment, extended DAPT significantly reduced the frequencies of myocardial infarction (OR 0.54 95% CI: 0.43-0.66; p<0.00001) and stent thrombosis (OR 0.36 95% CI: 0.24-0.55; p<0.00001), but the risks of major bleeding (OR 1.54 95% CI 1.22-1.96) and all-cause mortality (OR 1.43 95% CI 1.14-1.81) were substantially increased. There was no significant difference in stroke, cardiovascular mortality or repeat revascularization. Compared to short-term DAPT, 12-month DAPT or longer was associated with increased major bleeds (OR 1.98 95% CI: 1.26-3.11). No significant differences were found in the risk of other primary outcomes. CONCLUSION: 12-month DAPT appears to be a pragmatic compromise between preventing stent thrombosis and increasing bleeding risk. Patients at high bleeding risk should have shorter duration DAPT while those with low bleeding risk can be considered for DAPT beyond 12months. PMID- 27400192 TI - Barriers to Implementation of Optimal Laboratory Biosafety Practices in Pakistan. AB - The primary goal of biosafety education is to ensure safe practices among workers in biomedical laboratories. Despite several educational workshops by the Pakistan Biological Safety Association (PBSA), compliance with safe practices among laboratory workers remains low. To determine barriers to implementation of recommended biosafety practices among biomedical laboratory workers in Pakistan, we conducted a questionnaire-based survey of participants attending 2 workshops focusing on biosafety practices in Karachi and Lahore in February 2015. Questionnaires were developed by modifying the BARRIERS scale in which respondents are required to rate barriers on a 1-4 scale. Nineteen of the original 29 barriers were included and subcategorized into 4 groups: awareness, material quality, presentation, and workplace barriers. Workshops were attended by 64 participants. Among barriers that were rated as moderate to great barriers by at least 50% of respondents were: lack of time to read biosafety guidelines (workplace subscale), lack of staff authorization to change/improve practice (workplace subscale), no career or self-improvement advantages to the staff for implementing optimal practices (workplace subscale), and unclear practice implications (presentation subscale). A lack of recognition for employees' rights and benefits in the workplace was found to be a predominant reason for a lack of compliance. Based on perceived barriers, substantial improvement in work environment, worker facilitation, and enabling are needed for achieving improved or optimal biosafety practices in Pakistan. PMID- 27400193 TI - Factors associated with suicidal ideation disclosure: Results from a large population-based study. AB - BACKGROUND: It is crucial for clinicians and researchers to understand the factors associated with the disclosure of suicidal ideation. Describing the characteristics of those who do not disclose their suicidal ideation or who disclose their ideation only to close others, to health professionals or to both may help researchers and clinicians in their preventive efforts to treat persons at risk for suicidal behavior. METHODS: The sample was drawn from a large cross sectional survey (n=22,138) on mental health in France. The analyses were based on the 4,156 persons (17.1%) who endorsed lifetime suicidal ideation with or without a history of suicide attempt and who indicated whether and to whom they disclosed their ideation. Socio-demographics, current mental disorders, and social connectedness were assessed. RESULTS: Half of those with suicidal ideation had not shared their ideation with anyone, 6.3% did so with health professionals only, 20% with friends or family only, and 20% with both healthcare professionals and close others. Male gender, older age, lower education level and poor social connectedness were associated with greater odds of non-disclosure. Adjusting for socio-demographics and social connectedness, suicidal behavior and mental disorders were overall associated an increased likelihood of sharing suicidal ideation with health professionals. LIMITATIONS: Cross-sectional survey assessing lifetime suicidal ideation and disclosure. CONCLUSIONS: The findings provide important insight into the individual and social factors to take into account in suicidal ideation disclosure. PMID- 27400194 TI - Cytopathologic features of NUT midline carcinoma: A series of 26 specimens from 13 patients. AB - BACKGROUND: NUT midline carcinoma (NMC) is an increasingly recognized neoplasm defined by rearrangements of the nuclear protein in testis (NUT) gene (also known as NUTM1). NMC is important to diagnose for prognostic and diagnostic reasons, but to date, only a small case series and rare case reports of the cytopathologic features of NMC have been published. METHODS: All NMC specimens (confirmed by molecular testing and/or NUT immunoreactivity) with cytopathologic material available were identified at 2 academic centers. All smears were reviewed, and the cytologic characteristics were described. RESULTS: Twenty-six cytopathologic specimens of NMC were identified from 13 patients: 8 men and 5 women ranging in age from 16 to 68 years (mean, 35 years). The NMCs arose in the mediastinum (n = 4), sinonasal tract (n = 4), neck (n = 2), lung (n = 1), lung and mediastinum (n = 1), and kidney (n = 1). Cytologic specimens included serous cavity effusions (n = 13), fine-needle aspirates (n = 9), bronchial brushings (n = 2), bronchial lavage (n = 1), and bronchial washings (n = 1). Ancillary studies were performed on cell blocks for only 6 samples from 4 patients: immunohistochemistry (n = 6) and flow cytometry (n = 1). All 13 NMCs had corresponding surgical pathology material. The NUT rearrangement status was known in 10 cases, and in 3 cases, the diagnosis was established by immunoreactivity for NUT. On cytologic smears, the NMCs were mostly hypercellular with monotonous, small to midsize, primitive appearing cells largely distributed singly in a discohesive pattern. The tumor cells had round to oval nuclei that appeared mostly naked and devoid of cytoplasm. The nuclei varied in chromatin density from mostly pale, open chromatin to a hyperchromatic, neuroendocrine-type appearance, often with focal cell-to-cell molding, and most examples had a distinct, small nucleolus. CONCLUSIONS: NMC is a recently recognized tumor that should be considered in the differential diagnosis of small round cell tumors, especially but not exclusively in the mediastinum and the head and neck. The cytologic features of NMC overlap considerably with those of other neoplasms, and a definitive diagnosis depends on a demonstration of NUT translocation by either immunohistochemical or molecular means. Cancer Cytopathol 2016;124:901-908. (c) 2016 American Cancer Society. PMID- 27400196 TI - Laboratory monitoring of rivaroxaban and assessment of its bleeding risk. AB - BACKGROUND: The aims of this study were to investigate the effects of rivaroxaban on routine coagulation assays using our local, widely available, reagents and to study the relationship between sensitive coagulation assays and bleeding risk caused by rivaroxaban. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and anti-factor Xa (FXa) chromogenic assays (Biophen DiXaI) and inhibition of FXa activity were performed in normal pooled plasma (NPP) spiked with rivaroxaban and plasma samples from patients treated with rivaroxaban. RESULTS: In vitro, the linear correlation coefficient of measured concentrations of rivaroxaban, by Biophen DiXaI, and spiked concentrations of rivaroxaban was 0.99. PT and APTT showed good linear correlation with rivaroxaban concentrations, while other assays showed poor correlation. In vivo, PT showed a moderate linear correlation with rivaroxaban concentrations while APTT had a weak correlation with rivaroxaban concentrations. In vitro and in vivo, the rivaroxaban concentrations, measured by Biophen DiXaI, always showed good correlation with the inhibition of FXa activity, and PT values showed moderate correlation with the inhibition of FXa activity. CONCLUSIONS: Biophen DiXaI can be considered as a quantitative method to monitor the anticoagulation activity of rivaroxaban, and could be used to evaluate bleeding risk caused by rivaroxaban. The PT reagent (Thrombosis S) could be considered as a rough method to monitor the anticoagulation activity of rivaroxaban and evaluate bleeding risk caused by rivaroxaban. PMID- 27400195 TI - Interleukin (IL)-39 [IL-23p19/Epstein-Barr virus-induced 3 (Ebi3)] induces differentiation/expansion of neutrophils in lupus-prone mice. AB - Interleukin (IL)-12 family cytokines play critical roles in autoimmune diseases. Our previous study has shown that IL-23p19 and Epstein-Barr virus-induced 3 (Ebi3) form a new IL-12 family heterodimer, IL-23p19/Ebi3, termed IL-39, and knock-down of p19 or Ebi3 reduced diseases by transferred GL7+ B cells in lupus prone mice. In the present study, we explore further the possible effect of IL-39 on murine lupus. We found that IL-39 in vitro and in vivo induces differentiation and/or expansion of neutrophils. GL7+ B cells up-regulated neutrophils by secreting IL-39, whereas IL-39-deficient GL7+ B cells lost the capacity to up regulate neutrophils in lupus-prone mice and homozygous CD19cre (CD19-deficient) mice. Finally, we found that IL-39-induced neutrophils had a positive feedback on IL-39 expression in activated B cells by secreting B cell activation factor (BAFF). Taken together, our results suggest that IL-39 induces differentiation and/or expansion of neutrophils in lupus-prone mice. PMID- 27400198 TI - Letters. PMID- 27400199 TI - Brief reports. PMID- 27400197 TI - Evaluation of a Novel HA/ZrO2-Based Porous Bioceramic Artificial Vertebral Body Combined with a rhBMP-2/Chitosan Slow-Release Hydrogel. AB - A new HA/ZrO2-based porous bioceramic artificial vertebral body (AVB), carried a recombinant human bone morphogenetic protein-2 (rhBMP-2)/chitosan slow-release hydrogel was prepared to repair vertebral bone defect in beagles. An ionic cross linking was used to prepare the chitosan hydrogel (CS gel) as the rhBMP-2 slow release carrier. The vertebral body defects were implanted with the rhBMP-2 loaded AVB in group A, or a non-drug-loaded AVB in group B, or autologous iliac in group C. The encapsulation rate of rhBMP-2 in rhBMP-2-loaded CS gel was 91.88+/-1.53%, with a drug load of 39.84+/-2.34 ng/mg. At 6, 12, 24 weeks postoperatively, radiography showed that the bone calluses gradually increased with time in group A, where the artificial vertebral body had completely fused with host-bone at 24 weeks after surgery. In group C, an apparent bone remodeling was occurred in the early stages, and the graft-bone and host-bone had also fused completely at 24 weeks postoperatively. In group B, fusion occurred less than in groups A and C. At 24 weeks after surgery, micro-computed tomography (Micro-CT) revealed that the volume of newly-formed bone in group A was significantly more than in group B (p<0.05). At 24 weeks after surgery, ultra-compressive strengths of the operated segments were 14.03+/-1.66 MPa in group A, 8.62+/-1.24 MPa in group B, and 13.78+/-1.43 MPa in group C. Groups A and C were both significantly higher than group B (p < 0.05). At 24 weeks postoperatively, the hard tissue sections showed that the AVB of group A had tightly fused with host bone, and that pores of the AVB had been filled with abundant nearly mature bone, and that the new bone structured similarly to a trabecular framework, which was similar to that in group C. In contrast, implant fusion of the AVB in group B was not as apparent as group A. In conclusion, the novel HA/ZrO2-based porous bioceramic AVB carried the rhBMP-2-loaded CS gel can promote the repair of bony defect, and induce bone tissue to grow into the pores, which may replace iliac bone grafts as commonly applied in clinical practice. PMID- 27400202 TI - Running wild. PMID- 27400200 TI - A need to know. PMID- 27400203 TI - Editorial. PMID- 27400204 TI - ACSM Symposium: Former Athletes in Later Life. PMID- 27400205 TI - Effect of Fitness on Aging. AB - It's not the fountain of youth, but continued training in an athlete's later years may reduce the decline in fitness that has been attributed to aging. According to this study, the decline is actually the result of sedentary living. PMID- 27400206 TI - Former Professional Athletes' Adjustment to Retirement. AB - We often hear of retired professional athletes who become derelicts, alcoholics, commit suicide, or live in the past and can't hold a job. However, that's not the whole story. PMID- 27400208 TI - Cme credit quiz. PMID- 27400207 TI - The Longevity and Morbidity of College Athletes. AB - This well-designed study does not prove that athletic participation affects longevity and morbidity. Perhaps the same study of highly trained athletes would produce different results. PMID- 27400209 TI - Isokinetic Evaluation Following Leg Injuries. AB - Isokinetic strength testing, an objective method of quantifying a muscle's dynamic strength throughout its range of motion, is useful for diagnosis and for determining when an athlete can return to competition after injury. PMID- 27400210 TI - The Fitness Boom: Hucksters Ride the Bandwagon. AB - Pushed by big business and advertising agencies, fashionable fitness and aerobic chic have gathered the momentum of a huge, glittering bandwagon-with an impact on health that's both good and bad. PMID- 27400211 TI - Scanning sports. PMID- 27400212 TI - Action arena. PMID- 27400214 TI - Trainer's corner. PMID- 27400216 TI - The design and experiment of a novel ultrasonic motor based on the combination of bending modes. AB - This paper presents a new-type linear ultrasonic motor which takes advantage of the combination of two orthogonal bending vibration modes. The proposed ultrasonic motor consists of eight pieces of PZT ceramic plates and a metal beam that includes two cone-shaped horns and a cylindrical driving foot. The finite element analyses were finished to verify the working principle of the proposed motor. The mode shapes of the motor were obtained by modal analysis; the elliptical trajectories of nodes on the driving foot were obtained by time-domain analysis. Based on the analyses, a prototype of the proposed motor was fabricated and measured. The mechanical output characteristics were obtained by experiments. The maximal velocity of the proposed motor is 735mm/s and the maximal thrust is 1.1N. PMID- 27400217 TI - Survey of advanced nuclear technologies for potential applications of sonoprocessing. AB - Ultrasonics has been used in many industrial applications for both sensing at low power and processing at higher power. Generally, the high power applications fall within the categories of liquid stream degassing, impurity separation, and sonochemical enhancement of chemical processes. Examples of such industrial applications include metal production, food processing, chemical production, and pharmaceutical production. There are many nuclear process streams that have similar physical and chemical processes to those applications listed above. These nuclear processes could potentially benefit from the use of high-power ultrasonics. There are also potential benefits to applying these techniques in advanced nuclear fuel cycle processes, and these benefits have not been fully investigated. Currently the dominant use of ultrasonic technology in the nuclear industry has been using low power ultrasonics for non-destructive testing/evaluation (NDT/NDE), where it is primarily used for inspections and for characterizing material degradation. Because there has been very little consideration given to how sonoprocessing can potentially improve efficiency and add value to important process streams throughout the nuclear fuel cycle, there are numerous opportunities for improvement in current and future nuclear technologies. In this paper, the relevant fundamental theory underlying sonoprocessing is highlighted, and some potential applications to advanced nuclear technologies throughout the nuclear fuel cycle are discussed. PMID- 27400218 TI - Analyses of the role of the glucocorticoid receptor gene polymorphism (rs41423247) as a potential moderator in the association between childhood overweight, psychopathology, and clinical outcomes in Eating Disorders patients: A 6 years follow up study. AB - Childhood overweight and the SNP rs41423247 of the glucocorticoid receptor gene (GR) were reported to represent predisposing factors for Eating Disorders (EDs). The distribution of the polymorphism was evaluated in 202 EDs patients, and in 116 healthy subjects. The Structured Clinical Interview for the DSM-IV and self reported questionnaires were administered at the admission to the clinic and at 3 time points (end of a cognitive behavioral therapy, 3 and 6 years follow up). G allele was associated with childhood overweight, depressive disorder comorbidity, and diagnostic instability. G-allele carriers reporting childhood overweight showed greater frequency of subjective binge eating and emotional eating. PMID- 27400219 TI - Predictors of change in psychosocial impairment secondary to an eating disorder. AB - Eating disorders (ED) can significantly impair psychosocial health in patients. However, no published studies have so far used a standardized and specific instrument to evaluate predictive factors in ED-related psychosocial impairment. This prospective cohort study involved 177 patients receiving outpatient treatment for an ED at baseline and 115 patients at the 1-year follow-up. Patients completed three self-administered questionnaires: the Clinical Impairment Assessment (CIA), the Eating Attitudes Test-12 (EAT-12), and the Health-Related Quality of Life in ED-short form (HeRQoLED-s). Descriptive statistics, ANOVA, chi-square, and Fisher's exact test were applied to examine intervariable relationships. Multivariate linear regression was used to determine predictors of change in CIA scores. An improvement was reported by patients with restrictive anorexia nervosa (AN) compared to those with purgative AN. In the multivariate analysis, employment status, subtype of ED, and the bulimia and food preoccupation factor of the EAT-12 were significant predictors of change in the CIA scores. PMID- 27400220 TI - The incremental validity of a computerised assessment added to clinical rating scales to differentiate adult ADHD from autism spectrum disorder. AB - There is a clinical need for objective evidence-based measures that are sensitive and specific to ADHD when compared with other neurodevelopmental disorders. This study evaluated the incremental validity of adding an objective measure of activity and computerised cognitive assessment to clinical rating scales to differentiate adult ADHD from Autism spectrum disorders (ASD). Adults with ADHD (n=33) or ASD (n=25) performed the QbTest, comprising a Continuous Performance Test with motion-tracker to record physical activity. QbTest parameters measuring inattention, impulsivity and hyperactivity were combined to provide a summary score ('QbTotal'). Binary stepwise logistic regression measured the probability of assignment to the ADHD or ASD group based on scores on the Conners Adult ADHD Rating Scale-subscale E (CAARS-E) and Autism Quotient (AQ10) in the first step and then QbTotal added in the second step. The model fit was significant at step 1 (CAARS-E, AQ10) with good group classification accuracy. These predictors were retained and QbTotal was added, resulting in a significant improvement in model fit and group classification accuracy. All predictors were significant. ROC curves indicated superior specificity of QbTotal. The findings present preliminary evidence that adding QbTest to clinical rating scales may improve the differentiation of ADHD and ASD in adults. PMID- 27400223 TI - Identification of a European interserotypic reassortant strain of infectious bursal disease virus. AB - Infectious bursal disease virus (IBDV, family Birnaviridae) is a bi-segmented double-stranded RNA virus for which two serotypes are described. Serotype 1 replicates in the bursa of Fabricius and causes an immunosuppressive and potentially fatal disease in young chickens. Serotype 2 is apathogenic in poultry species. Up to now, only one natural event of interserotypic reassortment has been described after the introduction of very virulent IBDV (vvIBDV) in the USA in 2009, resulting in an IBDV strain with its segment A related to vvIBDV and its segment B related to US serotype 2 strain OH. Here, we present the first European isolate illustrative of interserotypic reassortment. The reassorting isolate, named 100056, exhibits a genomic segment A typical of current European vvIBDV but a segment B close to European serotype 2 viruses, supporting an origin distinct from US strains. When inoculated into SPF chickens, isolate 100056 induced mild clinical signs in the absence of mortality but caused a severe bursal atrophy, which strongly suggests an immunosuppressive potential. These results illustrate that interserotypic reassortment is another mechanism that can create IBDV strains with a modified acute pathogenicity. As a consequence, and for a more precise inference of the possible phenotype, care should be taken that the molecular identification of IBDV strains is targeted to both genome segments. PMID- 27400222 TI - Reinduction with Certolizumab Pegol in Patients with Crohn's Disease Experiencing Disease Exacerbation: 7-Year Data from the PRECiSE 4 Study. AB - BACKGROUND: Patients with Crohn's disease in whom tumor necrosis factor antagonist therapy fails have limited treatment options, and the benefit of reintroducing the same therapy remains unclear. Here, we report results from PRECiSE 4 (NCT00160706), an open-label extension study of certolizumab pegol in patients who withdrew from the placebo-controlled studies PRECiSE 1 or 2. METHODS: Patients eligible for PRECiSE 4 had Crohn's disease exacerbation on placebo or primary or secondary failure to certolizumab pegol in PRECiSE 1 or 2, and received 400 mg certolizumab pegol subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter up to 360 weeks. We assessed safety (adverse events) and efficacy (clinical remission) of extended certolizumab pegol therapy. RESULTS: Patients enrolled in PRECiSE 4 (N = 310; mean age, 37 yr; 58% female; 95% white) had a mean Crohn's disease duration of 8.5 years before entering the qualifying studies. At weeks 52, 104, and 156, remission rates were 28.5%, 17.5%, and 12.6% by nonremitter imputation, and 63.8%, 60.0%, and 63.5% by observed cases, with 47.4%, 31.9%, and 23.2% of patients, respectively, remaining on therapy. By study end (7.5 yr), 92.3% of patients discontinued therapy, 49% on account of adverse events. No new safety signals emerged. Incidence rate (new cases)/100 patient years was 6.11 for serious infections and 1.29 for malignancies. CONCLUSIONS: Certolizumab pegol was effective in many patients who previously discontinued certolizumab pegol for lack or loss of response. Thus, discontinuation of therapy may not always be necessary. Safety was consistent with previous findings. PMID- 27400224 TI - A Study of Abeta Oligomers in the Temporal Cortex and Cerebellum of Patients with Neuropathologically Confirmed Alzheimer's Disease Compared to Aged Controls. AB - BACKGROUND/AIMS: Investigations of Abeta oligomers in neuropathologically confirmed Alzheimer's disease (AD) are still scarce. We report neurohistopathological and biochemical analyses using antibodies against tau and amyloid beta (Abeta) pathology. METHODS: Thirty elderly AD patients and 43 age matched controls with or without deposition of amyloid plaques (AP) were analyzed by immunohistochemistry. In 21 cases with available fresh tissue, Western blots were also performed. Neuropathological analysis included quantitative assessment of neurofibrillary tangles (NFT), AP and Abeta oligomer densities in the mesial temporal cortex (TC). RESULTS: NFT, fibrillar amyloid and Abeta oligomeric deposit densities were significantly higher in AD patients than in controls. There was no relationship between oligomeric Abeta densities and Braak NFT staging scores. Furthermore, Abeta oligomer expression was closely correlated with Abeta plaques in the TC. By Western blot, Abeta oligomers were observed in AD patients, in plaque-free controls, in 1 'tangle-only AD' case, as well as in the cerebellum. A band near 55 kDa was the only Western blot signal that was significantly increased in the TC of AD patients compared to controls as well as less expressed in the cerebellum. CONCLUSION: These results suggest that a putative dodecamer, near 55 kDa, may contribute to AD vulnerability of the TC. PMID- 27400226 TI - Canine Infections and Partial S Segment Sequence Analysis of Toscana Virus in Turkey. AB - INTRODUCTION: Toscana virus (TOSV) is a sandfly-borne bunyavirus with a significant public health impact. Preliminary studies have revealed TOSV exposure in dogs and they were suggested as potential reservoirs. This study was performed to characterize canine TOSV infections in an endemic region. Sequencing of TOSV small (S) segment in several previously identified specimens was also undertaken to reveal viral genealogy. MATERIALS AND METHODS: Canine and feline plasma were collected in several districts of Mersin province, Mediterranean Anatolia, Turkey, during May-September, 2015. Phlebovirus RNA was screened through two nested polymerase chain reaction (PCR) assays, targeting S and large (L) segments of the viral genome. A kinetoplast minicircle nested PCR was employed for Leishmania DNA detection and typing. Previously collected TOSV-positive specimens from humans, dogs, cats, and sandflies from various regions in Turkey and Cyprus were further evaluated through the S segment PCR. All amplicons were characterized through sequencing. RESULTS: A total of 210 specimens that comprise canine (76.2%) and feline (23.8%) plasma were screened. In three (1.9%) and two (1.3%) canine specimens, TOSV and Leishmania nucleic acids were detected, respectively. The TOSV strains were characterized as genotype B, and Leishmania infantum was identified in positive specimens. Twenty-four partial S segment sequences were amplified, which demonstrated a maximum intramural diversity of 3.88% in the nucleotide level. Sequence comparisons revealed significant similarities to particular genotype B strains characterized in Spain and France, whereas a notable divergence was observed among several TOSV strains. Single or recurrent amino acid substitutions were noted in eight residues of the viral nucleocapsid. DISCUSSION: Canine infections of TOSV genotype B, with temporal and spatial association with L. infantum, were detected. Divergent TOSV S segment sequences with amino acid substitutions, presumably associated with host adaptation, were observed. PMID- 27400227 TI - Combining Diffusion Tensor Imaging and Susceptibility Weighted Imaging on the Substantia Nigra of 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPTP) induced Rhesus Monkey Model of Parkinson's Disease. AB - Objective: The aim of this study was to evaluate whether combining diffusion tensor magnetic resonance imaging (DTI) and susceptibility weighted imaging (SWI) techniques would provide a sensitive method for differentiating between 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rhesus monkey model of Parkinson's disease (PD) and wild-type controls. Subjects and Methods: Seventeen rhesus monkeys were divided into two groups. A series of intramuscular injections of either saline (control group, n = 8) or MPTP (0.2 mg/kg body weight; PD group, n = 9) were given to the monkeys, twice a week. Then, SWI and DTI scans were obtained from the monkeys with Siemens Magnetom Verio 3.0T superconductive MRI system. Region of interest analysis was performed on substantia nigra pars compacta (SNc) and substantia nigra pars reticulata (SNr). In addition, immunohistochemical staining of tyrosine hydroxylase was applied to assess degeneration of SN dopaminergic neurons. Results: Monkeys in the PD group displayed mild to moderate motor symptoms assessed using Kurlan's scale. With SWI scans, decreased width of SNc but increased width of SNr was found in PD group monkeys compared to controls. Calculation of the ratios of widths of SNc and SNr to the anterior and posterior mesencephalic diameter also reflected narrower SNc but wider SNr than controls. Decreased SWI signal intensity of SNc and SNr suggested iron deposition in both subregions of SN. The DTI scans showed lower fractional anisotropy (FA) values in SNc of the PD group monkeys, while no change of FA values in SNr was detected. Immunohistochemical test displayed generalized loss of dopaminergic neurons in SN of PD group monkeys. Conclusion: Combining the use of DTI and SWI can provide a sensitive method for differentiating between MPTP-induced rhesus monkey model of PD and wild-type controls. This effective imaging modality might provide additional information for characteristic identification of PD at early stages, thus enhancing the ability to make early diagnosis, and monitor progression of the natural history and treatment effects. PMID- 27400228 TI - Introducing Open Highlights: Highlighting Open Access Research from PLOS and Beyond. AB - PLOS Biology announces a new article type, Open Highlights, which uses a recent research article to nucleate a short synthesis of up to ten related research articles from other PLOS journals and from the wider Open Access corpus. PMID- 27400229 TI - Thermocapillary Migration of Liquid Droplets Induced by a Unidirectional Thermal Gradient. AB - A liquid droplet placed on a nonuniformly heated solid surface will migrate from a high-temperature region to a low-temperature region. This study reports the development of a theoretical model and experimental investigation on the migration behavior of paraffin oil droplets induced by the unidirectional thermal gradient. Thin-film lubrication theory is employed to determine the migration velocity of droplets, and temperature dependence of viscosity is taken into account. Comparisons between experimental and numerical results are presented. An effective approach for estimating the thermocapillary migration velocity of droplets on lubrication is proposed. PMID- 27400230 TI - Impacts of Surface Energy on Lithium Ion Intercalation Properties of V2O5. AB - Oxygen vacancies have demonstrated to be one of the most effective ways to alter electrochemical performance of electrodes for lithium ion batteries, though there is little information how oxygen vacancies affect the electrochemical properties. Vanadium pentoxide (V2O5) cathode has been investigated to explore the relationship among oxygen vacancies, surface energy, and electrochemical properties. The hydrogen-treated V2O5 (H-V2O5) sample synthesized via thermal treatment under H2 atmosphere possesses a high surface energy (63 mJ m(-2)) as compared to that of pristine V2O5 (40 mJ m(-2)) and delivers a high reversible capacity of 273.4 mAh g(-1) at a current density of 50 mA g(-1), retaining 189.0 mAh g(-1) when the current density increases to 2 A g(-1). It also displays a capacity retention of 92% after 100 cycles at 150 mA g(-1). The presence of surface oxygen vacancies increases surface energy and possibly serves as a nucleation center to facilitate phase transition during lithium ion intercalation and deintercalation processes. PMID- 27400231 TI - Effects of Oleanane-Type Triterpene Saponins from the Leaves of Eleutherococcus senticosus in an Axonal Outgrowth Assay. AB - An aqueous extract of Eleutherococcus senticosus leaves exerted a beneficial effect in restoring the neurite outgrowth from Abeta25-35-induced degeneration using an axonal density assay. Subsequent bioassay-guided fractionation afforded seven new oleanane-type triterpene saponins, ezoukoginosides A-G (1-7), along with nine known analogues. The structures of 1-7 were elucidated through chemical and spectroscopic approaches, and their effects on restoring the neurite outgrowth from Abeta25-35-induced degeneration were investigated. The results revealed that hydrophilic oleanane-type saponins substituted with a free carboxylic acid, hydroxy, or formyl group in the aglycone, especially when the oxidation occurred at C-29, not only restrained Abeta25-35-induced degeneration but also restored axonal outgrowth significantly. Compounds 2 (-COOH at C-29) and 3 (-CH2OH at C-29) showed the most potent bioactivity among the isolates. PMID- 27400232 TI - Biochemical and synthetic biology approaches to improve photosynthetic CO2 fixation. AB - There is an urgent need to improve agricultural productivity to secure future food and biofuel supply. Here, we summarize current approaches that aim at improving photosynthetic CO2-fixation. We critically review, compare and comment on the four major lines of research towards this aim, which focus on (i) improving RubisCO, the CO2-fixing enzyme in photosynthesis, (ii) implementing CO2 concentrating mechanisms, (iii) establishing synthetic photorespiration bypasses, and (iv) engineering synthetic CO2-fixation pathways. PMID- 27400233 TI - Protection Against Spikes in Workload With Aerobic Fitness and Playing Experience: The Role of the Acute:Chronic Workload Ratio on Injury Risk in Elite Gaelic Football. AB - PURPOSE: To examine the association between combined session rating of perceived exertion (RPE) workload measures and injury risk in elite Gaelic footballers. METHODS: Thirty-seven elite Gaelic footballers (mean +/- SD age 24.2 +/- 2.9 y) from 1 elite squad were involved in a single-season study. Weekly workload (session RPE multiplied by duration) and all time-loss injuries (including subsequent-wk injuries) were recorded during the period. Rolling weekly sums and wk-to-wk changes in workload were measured, enabling the calculation of the acute:chronic workload ratio by dividing acute workload (ie, 1-weekly workload) by chronic workload (ie, rolling-average 4-weekly workload). Workload measures were then modeled against data for all injuries sustained using a logistic regression model. Odds ratios (ORs) were reported against a reference group. RESULTS: High 1-weekly workloads (>=2770 arbitrary units [AU], OR = 1.63-6.75) were associated with significantly higher risk of injury than in a low-training load reference group (<1250 AU). When exposed to spikes in workload (acute:chronic workload ratio >1.5), players with 1 y experience had a higher risk of injury (OR = 2.22) and players with 2-3 (OR = 0.20) and 4-6 y (OR = 0.24) of experience had a lower risk of injury. Players with poorer aerobic fitness (estimated from a 1-km time trial) had a higher injury risk than those with higher aerobic fitness (OR = 1.50-2.50). An acute:chronic workload ratio of (>=2.0) demonstrated the greatest risk of injury. CONCLUSIONS: These findings highlight an increased risk of injury for elite Gaelic football players with high (>2.0) acute:chronic workload ratios and high weekly workloads. A high aerobic capacity and playing experience appears to offer injury protection against rapid changes in workload and high acute:chronic workload ratios. Moderate workloads, coupled with moderate to high changes in the acute:chronic workload ratio, appear to be protective for Gaelic football players. PMID- 27400234 TI - Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients' Outcome in Basal-Like Breast Cancer. AB - NDRG2, a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro, we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P<0.001) expression loss of NDRG2 in breast tumors. Of interest, basal-like tumors more frequently retained abundant NDRG2 expression concordant with a lower CpG-hypermethylation. Unexpectedly, basal-like breast cancer revealed an association of NDRG2 expression with unfavorable patients' outcome. In line with this observation, in vitro experiments demonstrated reduced proliferation and migration rates (~20%) in HCC1806 cells following NDRG2 silencing. In contrast, NDRG2 over-expressing luminal-type MCF7 cells demonstrated a 26% decreased proliferation rate. Until now, this is the first study investigating the putative role of NDRG2 in depth in basal-type breast cancer. Our data indicate that the described putative tumor suppressive function of NDRG2 may be confined to luminal- and basal B-type breast cancers. PMID- 27400235 TI - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Pilot Study to Evaluate the Utility of the ProCore Biopsy Needle for Lymph Node Sampling. AB - OBJECTIVE: The ProCore ultrasound biopsy needle, used primarily to obtain intra abdominal tissue core biopsies, has not been widely used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). In this pilot study we evaluated the utility of the ProCore needle for sampling mediastinal or hilar lymph nodes during EBUS-TBNA. DESIGN: Thirty-two patients were identified using both ProCore and conventional fine-needle aspiration (FNA) needles for sampling mediastinal or hilar lymph nodes (the study group). Another 33 patients underwent EBUS-TBNA using an FNA needle only (the control group). Specimen satisfactory rates were compared between the study and control groups. Aspirate smears and cell blocks were evaluated for the cellularity of lesional cells and bronchial contamination in a subset of patients in the study group. RESULTS: Overall, the ProCore needle did not show additive value to specimen adequacy when comparing the satisfactory rates of the study and control groups (94 vs. 89%). The ProCore needle also did not procure significantly more lesional cells than the FNA needle. CONCLUSION: Our experience shows that the ProCore needle does not provide additive value when performing an FNA of mediastinal or hilar lymph nodes. The evaluation of more cases with this new technique is necessary to better determine the clinical utility of using ProCore during EBUS-TBNA. PMID- 27400236 TI - Determination of Three Corticosteroids in the Biologic Matrix of Vitreous Humor by HPLC-tandem Mass Spectrometry: Method Development and Validation. AB - PURPOSE: To develop a simple, specific, and rapid method to determine corticosteroid concentrations in vitreous humor. METHODS: An analytical method based on high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS) with a simple extraction procedure was developed. New Zealand albino rabbits (n = 54) received a single (0.1 mL) intravitreal injection of dexamethasone (DXM, 0.1 mg), methylprednisolone (MP, 2 mg), or triamcinolone acetonide (TA, 10 mg). Eyes were enucleated and mean vitreous steroid levels were quantified at 12 h and 1, 2, 3, 7, and 14 days. RESULTS: Corticosteroids were extracted from the vitreous with acetonitrile, and TA was extracted with ethyl acetate, yielding high protein precipitation and clean solution samples. Vitreous samples were analyzed by isocratic HPLC-MS with mobile phase comprising acetonitrile and 2 mM ammonium formate buffer in water, pH 3.5. The linear range was 50-100,000 ng/g with a lower quantification limit of 45 ng/g for DXM and MP, and 50 ng/g for TA. Vitreous levels of DXM and MP were not detectable 14 days post-administration. Vitreous levels of TA were positive and stable throughout the study in both injected and control eyes. CONCLUSIONS: The HPLC-MS analytical method is an alternative to HPLC-MS/MS methods, sensitive enough for identifying and quantifying steroids in vitreous humor at a therapeutic dosage scale. PMID- 27400239 TI - The Danger of Not Treating Parkinson Disease Psychosis-Reply. PMID- 27400240 TI - Can subjective comfort be used as a measure of plantar pressure in football boots? AB - Comfort has been shown to be the most desired football boot feature by players. Previous studies have shown discomfort to be related to increased plantar pressures for running shoes which, in some foot regions, has been suggested to be a causative factor in overuse injuries. This study examined the correlation between subjective comfort data and objective plantar pressure for football boots during football-specific drills. Eight male university football players were tested. Plantar pressure data were collected during four football-specific movements for each of three different football boots. The global and local peak pressures based on a nine-sectioned foot map were compared to subjective comfort measures recorded using a visual analogue scale for global discomfort and a discomfort foot map for local discomfort. A weak (rs = -0.126) yet significant (P < 0.05) correlation was shown between the peak plantar pressure experienced and the visual analogue scale rated comfort. The model only significantly predicted (P > 0.001) the outcome for two (medial and lateral forefoot) of the nine foot regions. Subjective comfort data is therefore not a reliable measure of increased plantar pressures for any foot region. The use of plantar pressure measures is therefore needed to optimise injury prevention when designing studded footwear. PMID- 27400237 TI - Increased phosphate uptake but not resorption alleviates phosphorus deficiency induced by nitrogen deposition in temperate Larix principis-rupprechtii plantations. AB - The imbalance between nitrogen (N) and phosphorus (P) deposition may shift temperate ecosystems from N- to P-limitation. However, it is unclear how the imbalanced N : P input affects the strategies of plants to acquire P and, therefore, the growth of plants and the competition among species. We conducted a 4-yr N-addition experiment in young and mature larch (Larix principis rupprechtii) stands. Plant growth and P acquisition strategies were assessed for larch and understorey vegetation. N addition stimulated the aboveground productivity of understorey vegetation in the young stand and larch in the mature stand, with other species unaffected. The competitive advantages of understorey vegetation in the young stand and larch in the mature stand were associated with their high stoichiometric homoeostasis. To maintain the N : P homoeostasis of these species, an increase in phosphatase activity but not P resorption efficiency increased the supply of P. Additionally, N addition accelerated P mineralization by decreasing the fungal-to-bacterial ratios and improved uptake of soil P by increasing the arbuscular mycorrhizas-to-ectomycorrhizas ratios. Our results suggest that plants with high stoichiometric homoeostasis could better cope with N deposition-induced P-deficiency. Although P resorption efficiency showed little plasticity in response, plants activated a variety of P-acquisition pathways to alleviate the P-deficiency caused by N deposition. PMID- 27400241 TI - Effective approach towards Si-bilayer-IDA modified CoFe2O4 magnetic nanoparticles for high efficient protein separation. AB - Ultrafine cobalt ferrite (CoFe2O4) nanoparticles with narrow size distributions and regular morphologies were prepared through an improved procedure based on the high-temperature diol reduction method. By replacing the original reducing agent like expensive dihydric alcohol, oleylamine was applied as both stabilizer and reducing agent, which benefit for large scale synthesis of magnetic CoFe2O4 nanoparticles. To produce protein-separation agent with both high specific surface area and magnet content, inverse microemulsion system and substitution reaction were employed to render the produced CoFe2O4 nanoparticles with dense silica bilayer and iminodiacetic acid (IDA)-like structure modification. After the chelation with Cu(2+), the metal-immobilized CoFe2O4 nanoparticles can specifically absorb bovine hemoglobin (BHb) with maximum adsorption capacity as qm=1812.3mg/g. Compared with the reported Cu(2+)-immobilized magnetic nanoparticles, the as-prepared CoFe2O4@Si-IDA-Cu(2+) nanoparticles exhibited excellent adsorption capacity and were applied as high efficient protein separation agent in a real complex biological fluid like bovine blood. PMID- 27400242 TI - The effect of oil-water partition coefficient on the distribution and cellular uptake of liposome-encapsulated gold nanoparticles. AB - The shape, size, and surface features of nanoparticles greatly influence the structure and properties of resulting hybrid nanosystems. In this work, gold nanoparticles (GNPs) were modified via S-Au covalent bonding by glycol monomethyl ether thioctate with poly(ethylene glycol) methyl ether of different molecular weights (i.e., 350, 550, and 750Da). These modified GNPs (i.e., GNP350, GNP550, and GNP750) showed different oil-water partition coefficients (Kp), as detected using inductively coupled plasma-atomic emission spectroscopy. The different Kp values of the gold conjugates (i.e., 13.98, 2.11, and 0.036 for GNP350, GNP550, and GNP750, respectively) resulted in different conjugate localization within liposomes, as observed by transmission electron microscopy. In addition, the cellular uptake of hybrid liposomes co-encapsulating gold conjugates and Nile red was evaluated using intracellular fluorescence intensity. The results indicated that precise GNP localization in the hydrophilic or hydrophobic liposome cavity could be achieved by regulating the GNP oil-water partition coefficient via surface modification; such localization could further affect the properties and functions of hybrid liposomes, including their cellular uptake profiles. This study furthers the understanding not only of the interaction between liposomes and inorganic nanoparticles but also of adjusting liposome-gold hybrid nanostructure properties via the surface chemistry of gold materials. PMID- 27400243 TI - The application of prodrug-based nano-drug delivery strategy in cancer combination therapy. AB - Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. PMID- 27400244 TI - Total Synthesis of the Illicium-Derived Sesquineolignan Simonsol C. AB - The racemic form of the title natural product 1 has been synthesized by engaging, as a key step, the iodoarene-tethered cyclohexene 22 in an intramolecular Heck reaction to give compound 23. This angularly substituted tetrahydrodibenzo[b,d]furan was elaborated over a further five steps into target (+/-)-1. PMID- 27400245 TI - The Relationship between Sexual Cues and Sexual Desire in Women. AB - Sexual desire is one of the most studied dimensions of sexual response. There is extensive research on bio-medical, psychosocial, and relationship predictors of desire particularly in women. Despite this accumulated knowledge, there is a lack of studies investigating the ability of sexual cues to predict sexual desire. A sample of 546 heterosexual and premenopausal Portuguese women, aged between 18 and 53 years old, completed a web survey assessing socio-demographic variables, medical conditions, psychopathology, relationship dimensions, sexual cues and sexual desire. Findings from hierarchical regression analyses indicated that sexual cues significantly predict sexual desire. In particular, explicit/arousal cues (beta = .321, p < .001) were the most significant predictor of female sexual desire. Additionally, somatization (beta = .188, p < .001), relationship satisfaction (beta = .159, p < .001), anxiety (beta = -.165, p = .006), and antidepressant medication (beta = -.094, p = .014) were also significant predictors. Results emphasize the strong ability of explicit/arousal cues to predict sexual desire in women above and beyond other known factors. These findings suggest that the assessment of sexual desire problems in women as well as treatment approaches should take into consideration the role of sexual cues and particularly explicit/arousal cues. PMID- 27400246 TI - A qualitative national focus group study of the experience of living with lymphoedema and accessing local multiprofessional lymphoedema clinics. AB - AIM: The aim of this study was to explore people's experiences of living with lymphoedema and to assess the impact of access to local lymphoedema clinics on their condition and thus their lives. BACKGROUND: A chronic condition caused by reduced lymphatic function, lymphoedema leads to swelling, pain and mobility problems and can adversely affect quality-of-life. It is of international concern as its prevalence is rising. Yet lymphoedema awareness is limited, diagnostic delay common and access to specialist treatment restricted. The concept of local lymphoedema clinics is gaining support and in 2011 the All Wales Lymphoedema Service was founded. However, empirical investigation of local lymphoedema services remains limited. DESIGN: A qualitative exploratory study consisting of focus group interviews in every Welsh lymphoedema clinic (n = 8). METHODS: A convenience sample of adults living with lymphoedema in Wales was recruited. Data were collected in digitally recorded focus groups during July and August 2013. Interviews were fully transcribed and analysed using a qualitative content approach. FINDINGS: Fifty-nine people participated in eight focus groups. Analysis revealed three themes: Living with lymphoedema is a battle; delays in obtaining a correct diagnosis and the positive impact of lymphoedema clinics on participants' lives. Locally accessible clinics made meaningful differences to peoples' lymphoedema, engendered positive outcomes and improved engagement with and adherence to lymphoedema self-management. CONCLUSIONS: Local specialist lymphoedema clinics can make a positive difference. They may be cost-effective and further investigation, including economic evaluation is necessary. PMID- 27400247 TI - The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. AB - INTRODUCTION: Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndromes (MDS), but patients who relapse or are refractory have a poor prognosis with an estimated survival of 4-6 months. Rigosertib, a Ras mimetic that inhibits the phophoinositide 3-kinase and polo like kinase pathways, has been tested in patients with higher-risk MDS following treatment with HMAs, where there are no approved second-line therapies. AREAS COVERED: This review will provide an overview of rigosertib, including safety and efficacy demonstrated in clinical trials. Expert commentary: There is an urgent need for new treatment options for patients who have failed or progressed on HMAs. Rigosertib is currently undergoing testing as a single agent in certain subsets of higher-risk MDS patients as well as in combination with azacitidine, where preliminary data show efficacy in patients with de novo MDS as well as HMA failures. PMID- 27400248 TI - Synthesis of Group IV Nanowires on Graphene: The Case of Ge Nanocrawlers. AB - In recent years, there has been a growing interest in using graphene as a synthesis platform for polymers, zero-dimensional (0D) materials, one-dimensional materials (1D), and two-dimensional (2D) materials. Here, we report the investigation of the growth of germanium nanowires (GeNWs) and germanium nanocrawlers (GeNCs) on single-layer graphene surfaces. GeNWs and GeNCs are synthesized on graphene films by gold nanoparticles catalyzed vapor-liquid-solid growth mechanism. The addition of hydrogen chloride gas (HCl) at the nucleation step increased the propensity toward GeNCs growth on the surface. As the time lag before HCl introduction during the nucleation step increased, a significant change in the number of out-of-plane GeNWs versus in-plane GeNCs was observed. The nucleation temperature and time played a key role in the formation of GeNCs as well. The fraction of GeNCs (chiNCs) decreased from 0.95 +/- 0.01 to 0.66 +/- 0.07 when the temperature was kept at 305 degrees C for 15 s versus maintained at 305 degrees C throughout the process, respectively. GeNCs exhibit ?112? as the preferred growth direction whereas GeNWs exhibit both ?112? and ?111? as the preferred growth directions. Finally, our growth model suggests a possible mechanism for the preference of an in-plane GeNC growth on graphene versus GeNW on SiO2. These findings open up unique opportunities for fundamental studies of crystal growth on graphene, as well as enable exploration of new electronic interfaces between group IV materials and graphene, potentially toward designing new geometries for hybrid materials sensors. PMID- 27400249 TI - Nanoscale Structure and Elasticity of Pillared DNA Nanotubes. AB - We present an atomistic model of pillared DNA nanotubes (DNTs) and their elastic properties which will facilitate further studies of these nanotubes in several important nanotechnological and biological applications. In particular, we introduce a computational design to create an atomistic model of a 6-helix DNT (6HB) along with its two variants, 6HB flanked symmetrically with two double helical DNA pillars (6HB+2) and 6HB flanked symmetrically by three double helical DNA pillars (6HB+3). Analysis of 200 ns all-atom simulation trajectories in the presence of explicit water and ions shows that these structures are stable and well behaved in all three geometries. Hydrogen bonding is well maintained for all variants of 6HB DNTs. From the equilibrium bending angle distribution, we calculate the persistence lengths of these tubes. The measured persistence lengths of these nanotubes are ~10 MUm, which is 2 orders of magnitude larger than that of dsDNA. We also find a gradual increase of persistence length with an increasing number of pillars, in quantitative agreement with previous experimental findings. To have a quantitative understanding of the stretch modulus of these tubes, we carried out nonequilibrium steered molecular dynamics (SMD). The linear part of the force-extension plot gives a stretch modulus in the range 6500 pN for 6HB without pillars, which increases to 11 000 pN for tubes with three pillars. The values of the stretch modulus calculated using contour length distribution obtained from equilibrium MD simulations are similar to those obtained from nonequilibrium SMD simulations. The addition of pillars makes these DNTs very rigid. PMID- 27400250 TI - High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors. AB - The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38alpha kinase. PMID- 27400252 TI - Association of the microsatellite (GT)n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma. AB - CONCLUSION: Long (GT)n repeat polymorphisms in the heme oxygenase-1 (HO-1) gene promoter and decreased serum HO-1 levels are associated with a higher susceptibility to laryngeal squamous cell carcinoma (LSCC). OBJECTIVE: In this case-control study, the association of HO-1 microsatellite (GT)n repeat polymorphisms and serum levels with the risk of LSCC was investigated. METHODS: A total of 142 LSCC patients, 54 vocal leukoplakia patients and 98 healthy controls, were examined for (GT)n polymorphisms by sequencing, and the serum HO-1 levels were detected in a sub-set from participants above by ELISA. RESULTS: Compared with the controls, the LSCC group had significantly higher frequencies of L-allele (> 29 repeats) and L-allele carriers (p < 0.001, OR = 2.037 and p = 0.005, OR = 2.152, respectively). The frequencies of lymph node metastasis and of moderate or poor differentiation were significantly higher in L-allele carriers compared to non-L-allele carriers (p < 0.05). Significantly lower serum HO-1 levels were detected in LSCC patients (p < 0.001), and patients with lower serum HO-1 levels had more advanced cancer stage and a higher lymph node metastasis rate (p < 0.05). Furthermore, the L-allele carriers had lower serum HO-1 concentrations compared with the non-L-allele carriers (p = 0.019). PMID- 27400251 TI - Chemical modifications of amyloid-beta(1-42) have a significant impact on the repertoire of brain amyloid-beta(1-42) binding proteins. AB - The amyloid-beta peptide(1-42) (Abeta) is a key player in the development and progression of Alzheimer's disease (AD). Although much attention is paid to its role in formation of extracellular amyloid plaques and protein aggregates as well as to corresponding mechanisms of their toxicity, good evidence exists that intracellular Abeta can accumulate intraneuronally and interact with intracellular target proteins. However, intracellular Abeta binding proteins as well as conditions favoring their interactions with Abeta are poorly characterized. In this study we have investigated the effect of two known pathogenic Abeta modifications, isomerization of Asp7 and phosphorylation of Ser8, on the proteomic profiles of mouse brain Abeta binding proteins. Phosphorylation of Ser8 and especially isomerization of Asp7 significantly extended the repertoire of mouse brain Abeta binding proteins. However, there were 61 proteins, common for three types of the affinity ligands. They obviously represent potential targets for direct interaction with all Abeta species. Taking into consideration spontaneous mode of Asp7 isomerization and reports on initial accumulation of phosphorylated Abeta species inside neurons it is reasonable to suggest that these modifications of intracellular Abeta peptides causing the significant increase in the repertoire of Abeta binding proteins represent a primary pathogenic effect that precedes formation of extracellular pathogenic oligomerization/aggregation of Abeta peptides well described in the literature. PMID- 27400253 TI - Basilar Fracture Due to Frozen Corpse: A Case Report. AB - Basilar fractures are one of the consequences of craniocerebral injury, which is serious enough to cause death. Legal examiners often pay attention to basilar fractures at autopsy and analyze the relationship between them and death. It is noteworthy whether the fracture is premortem or postmortem. Here, we describe a rarely reported case of basilar fracture due to freezing. In this case, a 30-year old man was frozen (-18 degrees C) for 6 months after death. At autopsy, external examination showed no trauma. However, on internal examination, there was a basilar fracture which caused controversy but turned out to be a postmortem injury. We provide the case description and discussion on antemortem or postmortem basilar fractures as a differential for these cases. PMID- 27400254 TI - Stroke research at the crossroads - where are we heading? AB - Stroke causes 5.7 million deaths annually. This ranks stroke as the second most common cause of death and, additionally, it is a major cause of disability. Because of an ageing population, stroke incidence and costs will greatly increase in the future. This makes stroke an ongoing social and economic burden, in contrast to the only very limited therapeutic options. In the last decade vast sums were spent on translational research focused on neuroprotective strategies in the acute phase of ischaemic stroke. A plethora of candidate agents were tested in experimental models and preclinical studies, but none was proven effective in clinical trials. This gave rise to discussions about the possible reasons for this failure, ending up mainly with criticism of methodological aspects of the preclinical and clinical studies, or of the relevance of animal studies in drug development. Indeed, the question could rather be whether neuroprotection is the right target for successful stroke treatment. In this context, a paradigm change can currently be observed: the focus of experimental and translational stroke research is shifting from early neuroprotection to delayed mechanisms such as stroke-associated comorbidities, regeneration and plasticity. In this review we highlight a few recently emerging fields in translational stroke research. One such topic is the crosstalk between immunity and the injured brain as key pathomechanism in stroke. On one hand, innate and adaptive immune cells play an important role in the fate of injured brain tissue after stroke; on the other, peripheral immune alterations are critically involved in post-stroke comorbidities. Another emerging research area is the analysis of mechanisms involved in regeneration and neuronal plasticity after stroke. Here, we discuss the current understanding of basic mechanisms involved after brain injury, clinical imaging approaches and therapeutic strategies to promote regeneration in stroke patients. PMID- 27400255 TI - An Approach to the Estimation of Adsorption Enthalpies of Polycyclic Aromatic Hydrocarbons on Particle Surfaces. AB - Current atmospheric models incorporate the values of vaporization enthalpies, DeltaHvap, obtained for neat standards, thus disregarding the matrix effects on volatilization. To test the adequacy of this approximation, this study measured enthalpies of vaporization for five polycyclic aromatic hydrocarbons (PAHs) in the form of neat standards (DeltaHvap) as well as adsorbed on the surface of silica, graphite, and graphene particles (DeltaHvap(eff)), by using simultaneous thermogravimetry-differential scanning calorimetry (TGA-DSC). Measurement of the corresponding activation energy values, Ea(vap) and Ea vap(eff), by TGA using a derivative method was shown to be the most reliable and practical way to assess DeltaHvap and DeltaHvap(eff). Enthalpies of adsorption (DeltaHads) were then calculated from the differences between Ea(vap) and Ea vap(eff), thus paving a way to modeling the solid-gas phase partitioning in atmospheric particulate matter (PM). The PAH adsorption on silica particle surfaces (representing n-pi* interactions) resulted in negative values of DeltaHads, indicating significant interactions. For graphite particles, positive DeltaHads values were obtained; i.e., PAHs did not interact with the particle surface as strongly as observed for PM. PAHs on the surface of graphene particles evaporated in two stages, with the bulk of the mass loss occurring at temperatures lower than those with the neat standard, just as on graphite. Yet, unlike graphite, a small PAH fraction did not evaporate until higher temperatures compared to case of the neat standards and other particle surfaces (37.4-145.7 K), signifying negative, more PM-relevant values of DeltaHads, apparently reflecting pi-pi* interactions and ranging between -7.6 and +32.6 kJ mol(-1), i.e., even larger than for silica, -3.3 to +8.3 kJ mol(-1). Thus, current atmospheric models may underestimate the partitioning of organic species in the particle phase unless matrix adsorption is taken into account. PMID- 27400256 TI - This Is My Hospital's Performance on Quality of Care-No Excuses. PMID- 27400257 TI - Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification. AB - OBJECTIVES: Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. METHODS: Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. RESULTS: The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 MUg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 MUU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. CONCLUSIONS: Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP. PMID- 27400258 TI - Safety of Secretin Administration in Children. AB - OBJECTIVE: The aim of this study was to compare the hemodynamic parameters from the anesthesia records of children who underwent upper gastrointestinal endoscopy (esophagogastroduodenoscopy [EGD]) with and without secretin pancreatic function tests (sPFTs). METHODS: The hemodynamic parameters were retrieved from an electronic anesthesia database. The secretin group consisted of 186 children, and the age- and sex-matched control group included 136 patients who did not have sPFTs. RESULTS: There was no difference in the demographic parameters (age and sex) between the 2 groups. The secretin group had a lower height and body mass index. The sPFT resulted in an average 3-minute extension of the endoscopic procedure. The heart rate increased during the EGD in both groups and was higher (averaged 7 beats per minute) in the secretin group than the EGD-only group. There were mild elevations on the systolic and diastolic blood pressures. None of these changes were clinically significant. There were no complications reported during the anesthesia and procedures in the 2 groups. CONCLUSIONS: Secretin PFT is a safe procedure. It only slightly prolongs the total procedure and anesthesia time. There were no clinically significant changes in the vital parameters in the secretin group, and there were no adverse effects recorded. PMID- 27400259 TI - Portal Venous Blood Circulation Supports Immunosuppressive Environment and Pancreatic Cancer Circulating Tumor Cell Activation. AB - OBJECTIVES: Aggressive spread and liver metastases are predominant features of pancreatic ductal adenocarcinoma (PDAC). This study investigates activation of PDAC circulating tumor cells (CTC) and immunosuppression in the portal venous system. METHODS: Portal venous and peripheral blood were collected during pancreaticoduodenectomy from patients with PDAC (n = 21) or other non-PDAC pancreatic conditions (n = 20). Circulating tumor cells were isolated by fluorescence-activated cell sorting and characterized for messenger RNA (mRNA) expression and acetylated chromatin encoding K-RAS exon 12 mutation (K-RASmut). Myeloid-derived suppressor cells (MDSC) were identified using flow cytometry. RESULTS: Pancreatic ductal adenocarcinoma K-RASmut mRNA expression in portal venous blood CTC was significantly elevated compared with preoperative and postoperative peripheral blood (P = 0.0123 and P = 0.0246, respectively). There was no significant variation in total CTC numbers between portal and peripheral blood.Portal venous M-MDSC were elevated compared with peripheral blood in PDAC patients (P = 0.0065). M-MDSC increases correlated with K-RASmut mRNA-expressing CTC present in PDAC portal blood (P < 0.0001). CONCLUSIONS: Association of MDSC with active CTC in portal venous blood may support immunosuppression within the portal venous circulation to promote PDAC CTC survival. PMID- 27400260 TI - Alginate-containing systems for oral delivery of superoxide dismutase. Comparison of various configurations and their properties. AB - The regularities of release of therapeutic antioxidant enzyme superoxide dismutase (SOD) from various alginate-based delivery systems (DS) into simulated gastric and intestinal fluids were determined. The following systems were used: Ca-alginate granules (AG) prepared by various methods, porous carbonate cores with multilayer polyelectrolyte coating as well as the new two-level DS (Ca-AG containing carbonate cores loaded with proteins). The influence of the method of granule preparation, composition of gelation bath and ionic composition of the simulated fluids on release profiles of the protein from different DS was revealed. SEM images demonstrated changes in DS structures in various simulated fluids. The correlation between these changes and in vitro protein release was shown. The comparison of enzymatic activity of SOD encapsulated in DS of various configurations (including the systems containing different peptidase inhibitors) was made. The efficiency of protection of SOD activity in simulated intestinal fluid with trypsin was demonstrated. PMID- 27400261 TI - Strict Blood Pressure Control Achieved Using an ICT-Based Home Blood Pressure Monitoring System in a Catastrophically Damaged Area After a Disaster. AB - At the time of the Great East Japan earthquake and tsunami (March 2011), the authors developed a web-based information and communications technology (ICT) based blood pressure (BP) monitoring system (the Disaster CArdiovascular Prevention [DCAP] Network) and introduced it in an area that was catastrophically damaged (Minamisanriku town) to help control the survivors' BP. Using this system, home BP (HBP) was monitored and the data were automatically transmitted to a central computer database and to the survivors' attending physicians. The study participants, 341 hypertensive patients, continued to use this system for 4 years after the disaster and all of the obtained HBP readings were analyzed. This DCAP HBP-guided approach helped achieve a decrease in the participants' HBPs (initial average: 151.3+/-20.0/86.9+/-10.2 mm Hg to 120.2+/-12.1/70.8+/-10.2 mm Hg) over the 4 years. In addition, the amplitude of seasonal BP variation was suppressed and the duration from the summer lowest HBP values to the winter peak HBP values was gradually prolonged. This ICT-based approach was useful to achieve strict HBP control and minimize the seasonal BP variation even in a catastrophically damaged area during a 4-year period after the disaster, suggesting that this approach could be a routine way to monitor BP in the community. PMID- 27400262 TI - Increasing metronidazole and rifampicin resistance of Helicobacter pylori isolates obtained from children and adolescents between 2002 and 2015 in southwest Germany. AB - BACKGROUND: Increasing antibiotic resistance has been reported for Helicobacter pylori, but data on the prevalence of antibiotic resistance of H. pylori in pediatric patients and the development of resistance over time are sparse. METHODS: Data for 610 H. pylori isolates obtained between 2002 and 2015 from gastric biopsies of 582 (mainly treatment-naive) pediatric patients from southwest Germany were analyzed retrospectively regarding the antibiotic susceptibility determined by Etest and patients' characteristics. RESULTS: Overall resistance to metronidazole, clarithromycin, and rifampicin was 28.7%, 23.2%, and 13.3%, respectively, while resistance to amoxicillin was rare (0.8%). Simultaneous resistance to metronidazole and clarithromycin was observed for 7.7% of the isolates, and 2.3% were resistant to metronidazole, clarithromycin, and rifampicin. Differences between primary vs secondary resistance existed for metronidazole (24.7% vs 38.8%, P=.01) and clarithromycin (17.2% vs 54.1%, P=.0001). From 2002-2008 to 2009-2015, resistance to metronidazole increased from 20.8% to 34.4% (P=.003) and to rifampicin from 3.9% to 18.8% (P=.0001); this was not associated with increased numbers of patients previously treated for H. pylori infection in the second study period. In contrast, resistance to clarithromycin did not change significantly over time. Resistance was not associated with age, sex, or family origin in Europe. CONCLUSIONS: The considerable antibiotic resistance of H. pylori isolates argues for standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of antibiotic therapy. PMID- 27400263 TI - Emissions of Polycyclic Aromatic Hydrocarbons from Natural Gas Extraction into Air. AB - Natural gas extraction, often referred to as "fracking", has increased rapidly in the United States in recent years. To address potential health impacts, passive air samplers were deployed in a rural community heavily affected by the natural gas boom. Samplers were analyzed for 62 polycyclic aromatic hydrocarbons (PAHs). Results were grouped based on distance from each sampler to the nearest active well. Levels of benzo[a]pyrene, phenanthrene, and carcinogenic potency of PAH mixtures were highest when samplers were closest to active wells. PAH levels closest to natural gas activity were comparable to levels previously reported in rural areas in winter. Sourcing ratios indicated that PAHs were predominantly petrogenic, suggesting that PAH levels were influenced by direct releases from the earth. Quantitative human health risk assessment estimated the excess lifetime cancer risks associated with exposure to the measured PAHs. At sites closest to active wells, the risk estimated for maximum residential exposure was 0.04 in a million, which is below the U.S. Environmental Protection Agency's acceptable risk level. Overall, risk estimates decreased 30% when comparing results from samplers closest to active wells to those farthest from them. This work suggests that natural gas extraction is contributing PAHs to the air, at levels that would not be expected to increase cancer risk. PMID- 27400266 TI - beta-Alkyloxazolochlorins: Revisiting the Ozonation of Octaalkylporphyrins, and Beyond. AB - The reaction of beta-octaalkylporphyrins (octaethylporphyrin and etioporphyrin I) with ozone generated the corresponding heptaalkyloxazolochlorinhemiacetals in which a pyrrolic subunit of the porphyrins was replaced by an oxazoline moiety. Thus, a pyrrolic beta-carbon with its alkyl substituent was excised and replaced by an oxygen atom, and the neighboring beta-carbon was hydroxylated. This work clarifies the nature of the products first described by Fischer and Dezelic, in 1933, and verifies the work by Shulg'a and coworkers, from 1977. Furthermore, the chemistry of the oxazolochlorin hemiacetals was studied: They could be dehydroxylated or converted to alkyl acetals and gem-dialkyl derivatives, all possessing chlorin-type optical spectra. Their oxidative conversions generated a unique tetrahydrofuran-linked oxazolochlorin dimer and a hexaethylporpholactone. The work expands on the knowledge of converting porphyrins to porphyrinoids of potential utility containing nonpyrrolic building heterocycles. PMID- 27400265 TI - Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. AB - The biological effects of urolithins remain poorly characterized, despite wide spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We identified urolithin A (UA) as a first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption. In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan. Likewise, UA prolonged normal activity during aging in C. elegans, including mobility and pharyngeal pumping, while maintaining mitochondrial respiratory capacity. These effects translated to rodents, where UA improved exercise capacity in two different mouse models of age-related decline of muscle function, as well as in young rats. Our findings highlight the health benefits of urolithin A and its potential application in strategies to improve mitochondrial and muscle function. PMID- 27400264 TI - International AIDS Society global scientific strategy: towards an HIV cure 2016. AB - Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy. PMID- 27400268 TI - Direct Monitoring of beta-Sheet Formation in the Outer Membrane Protein TtoA Assisted by TtOmp85. AB - Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was applied to investigate the folding of an outer membrane protein, TtoA, assisted by TtOmp85, both from the thermophilic eubacterium Thermus thermophilus. To directly monitor the formation of beta-sheet structure in TtoA and to analyze the function of TtOmp85, we immobilized unfolded TtoA on an ATR crystal. Interaction with TtOmp85 initiated TtoA folding as shown by time-dependent spectra recorded during the folding process. Our ATR-FTIR experiments prove that TtOmp85 possesses specific functionality to assist beta-sheet formation of TtoA. We demonstrate the potential of this spectroscopic approach to study the interaction of outer membrane proteins in vitro and in a time-resolved manner. PMID- 27400267 TI - Integration of light and metabolic signals for stem cell activation at the shoot apical meristem. AB - A major feature of embryogenesis is the specification of stem cell systems, but in contrast to the situation in most animals, plant stem cells remain quiescent until the postembryonic phase of development. Here, we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot apical meristem. We show on the one hand that light is able to activate expression of the stem cell inducer WUSCHEL independently of photosynthesis and that this likely involves inter-regional cytokinin signaling. Metabolic signals, on the other hand, are transduced to the meristem through activation of the TARGET OF RAPAMYCIN (TOR) kinase. Surprisingly, TOR is also required for light signal dependent stem cell activation. Thus, the TOR kinase acts as a central integrator of light and metabolic signals and a key regulator of stem cell activation at the shoot apex. PMID- 27400269 TI - The Future of the Affordable Care Act: Reassessment and Revision. PMID- 27400271 TI - Chemical study of the fungus Psilocybe merdaria. AB - Chemical investigation on the cultures of the fungus Psilocybe merdaria resulted in the first isolation of 10 compounds including two new ones 11,14 dihydroxylneoechinulin E (1) and (S)-4-(4-methylpent-3-en-1-yl)-butyrolactone (2). Their structures were elucidated from the analysis of 1D and 2D NMR and MS data. Among them, compound 7 showed inhibitory activity against AChE with 20% percentage at a concentration of 50 MUg/ml. PMID- 27400270 TI - The Contribution of Gender to Apparent Sex Differences in Health Status Among Patients with Coronary Artery Disease. AB - BACKGROUND: While it has been identified that gender (socially manufactured roles, behaviors, expressions, and identities) plays a central role in men's and women's health, the distinction between gender and sex (biological attributes) has largely been ignored in health science research. The purpose of this study was to look at the unique contributions of sex, age, and the Gender Index (GI) to baseline health status in a cohort of patients with coronary artery disease (CAD). PARTICIPANTS AND METHODS: Questions that comprised the GI were included in the follow-up questionnaire sent to patients in the APPROACH registry. To examine the relationship between sex, gender, and health status, a sequential linear regression modeling approach was used. RESULTS: A total of 632 patients completed the GI between July and August 2015. The women were significantly older (68 years vs. 66 years, p = 0.02) and significantly more likely to have hypertension (50.8% vs. 38.8%, p = 0.02) compared to the men. Women reported significantly lower mean Seattle Angina Questionnaire (SAQ) scores compared to men. The inclusion of age into the models did not change the relationship between sex and the SAQ scales. However, the inclusion of the GI attenuated the relationship between sex and the SAQ scale scores. CONCLUSIONS: Our results support the concept that sex differences in health status outcomes may be better explained by patient's gender related characteristics, than biological sex characteristics. More importantly, the GI offers a pragmatic composite score to assess the effects of psychosocial factors that researchers interested in measuring gender could use in studies of subjects with CAD. PMID- 27400272 TI - High-dose atorvastatin is associated with lower IGF-1 levels in patients with type 1 diabetes. AB - INTRODUCTION: Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors, statins, in order to prevent vascular complications. Yet little is known about the effect of statins on the IGF-1/IGFBP-1 axis in these patients. OBJECTIVES: The aim of this study was to evaluate the effect of atorvastatin treatment on IGF 1 and IGFBP-1 with regards to microvascular function. DESIGN: Twenty patients with type 1 diabetes received either placebo or 80mg atorvastatin for two months in a double-blinded cross-over study. IGF-1 and IGFBP-1 levels were assessed before and after each treatment period. Skin microcirculation was studied using Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. RESULTS: Treatment with high-dose atorvastatin was associated with a significant decrease in IGF-1 levels compared to placebo (p<0.05, ANOVA repeated measures), whereas no effect was seen on IGFBP 1 or the IGF-1/IGFBP-1 ratio. These variables did not correlate with measurements of skin microvascular reactivity. CONCLUSIONS: The study found that treatment with high-dose atorvastatin was associated with reduced IGF-1 levels, which may indicate a potential negative effect on microvascular function and long-term risk of microangiopathy development. PMID- 27400273 TI - Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis. AB - OBJECTIVES: Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE. METHODS: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation. RESULTS: Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality. CONCLUSIONS: The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results. PMID- 27400274 TI - Tetrazole-Viologen-based Flexible Microporous Metal-Organic Framework with High CO2 Selective Uptake. AB - A flexible metal-organic framework (FMOF) with functionalized pores was hydrothermally synthesized to improve CO2 affinity and selectivity. The obtained FMOF exhibits a reversible shrinking and swelling framework transformation, which is triggered by the adsorption of CO2 rather than by the adsorption of N2 and CH4. At ambient temperature and an atmospheric pressure, this FMOF shows not only a high CO2 uptake (98 cm(3) g(-1), 19.3 wt %) but also a good calculated adsorption selectivity for CO2 over both CH4 and N2 (CO2/CH4 50:50 v/v: 28.6:1, CO2/N2 15:85 v/v: 210.4:1 calculated by ideal adsorbed solution theory), indicating potential applications in the purification of natural gas and industrial flue gas. PMID- 27400275 TI - Trends in Cancer-Center Spending on Advertising in the United States, 2005 to 2014. PMID- 27400276 TI - Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurones, which leads to paralysis and death in an average of 3 years following diagnosis. The cause of ALS is unknown, but there is substantial evidence that metabolic factors, including nutritional state and body weight, affect disease progression and survival. This review provides an overview of the characteristics of metabolic dysregulation in ALS focusing on mechanisms that lead to disrupted energy supply (at a whole-body and cellular level) and altered energy expenditure. We discuss how a decrease in energy supply occurs in parallel with an increase in energy demand and leads to a state of chronic energy deficit which has a negative impact on disease outcome in ALS. We conclude by presenting potential and tested strategies to compensate for, or correct this energy imbalance, and speculate on promising areas for further research. PMID- 27400277 TI - Pseudomonas sp. BUP6, a novel isolate from Malabari goat produces an efficient rhamnolipid type biosurfactant. AB - This study describes the characteristics of a biosurfactant produced by Pseudomonas sp. BUP6, a rumen bacterium, and optimization of parameters required for its production. Initial screening of five parameters (pH, temperature, agitation, incubation, and substrate concentration) was carried out employing Plackett-Burman design, which reduced the number of parameters to 3 (pH, temperature, and incubation) according to their significance on the yield of biosurfactant. A suitable statistical model for the production of biosurfactant by Pseudomonas sp. BUP6 was established according to Box-Behnken design, which resulted in 11% increase (at pH 7, 35 degrees C, incubation 75 h) in the yield (2070 mg L-1 ) of biosurfactant. The biosurfactant was found stable at a wide range of pH (3-9) with 48 mg L-1 critical micelle concentration; and maintained over 90% of its emulsification ability even after boiling and in presence of sodium chloride (0.5%). The highest cell hydrophobicity (37%) and emulsification (69%) indices were determined with groundnut oil and kerosene, respectively. The biosurfactant was found to inhibit the growth and adhesion of E. coli and S. aureus significantly. From the phytotoxicity studies, the biosurfactant did not show any adverse effect on the germinating seeds of rice and green gram. The structural characterization of biosurfactant employing orcinol method, thin layer chromatography and FT-IR indicated that it is a rhamnolipid (glycolipid). Thus, Pseudomonas sp. BUP6, a novel isolate from Malabari goat is demonstrated as a producer of an efficient rhamnolipid type biosurfactant suitable for application in various industries. PMID- 27400278 TI - Facile construction of pyrrolo[1,2-b]isoquinolin-10(5H)-ones via a redox amination-aromatization-Friedel-Crafts acylation cascade reaction and discovery of novel topoisomerase inhibitors. AB - An efficient redox-amination-aromatization-Friedel-Crafts acylation cascade process from trans-4-hydroxyproline and 2-formylbenzoic acids has been developed for the synthesis of pyrrolo[1,2-b]isoquinolin-10(5H)-ones. Compound 3h was identified as a new potent dual topoisomerase I/II inhibitor. PMID- 27400279 TI - Machine Learning Meta-analysis of Large Metagenomic Datasets: Tools and Biological Insights. AB - Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction tasks using quantitative microbiome profiles, including species-level relative abundances and presence of strain-specific markers. A comprehensive meta-analysis, with particular emphasis on generalization across cohorts, was performed in a collection of 2424 publicly available metagenomic samples from eight large-scale studies. Cross-validation revealed good disease-prediction capabilities, which were in general improved by feature selection and use of strain-specific markers instead of species-level taxonomic abundance. In cross-study analysis, models transferred between studies were in some cases less accurate than models tested by within-study cross-validation. Interestingly, the addition of healthy (control) samples from other studies to training sets improved disease prediction capabilities. Some microbial species (most notably Streptococcus anginosus) seem to characterize general dysbiotic states of the microbiome rather than connections with a specific disease. Our results in modelling features of the "healthy" microbiome can be considered a first step toward defining general microbial dysbiosis. The software framework, microbiome profiles, and metadata for thousands of samples are publicly available at http://segatalab.cibio.unitn.it/tools/metaml. PMID- 27400280 TI - White matter and reaction time: Reply to commentaries. AB - We appreciate the many comments we received on our discussion paper and believe that they reflect a recognition of the importance of this topic worldwide. We point out in this reply that there appears to be a confusion between the role of oscillations in creating white matter and other functions of oscillations in communicating between neural areas during task performance or at rest. We also discuss some mechanisms other than the enhancement of white matter that must influence reaction time. We recognize the limited understanding we have of transfer and outline some future directions designed to improve our understanding of this process. PMID- 27400281 TI - Telephone talk: effects of two access methods on phone call success. AB - The slower and unnatural timing of speech inherent to speech-generating devices (SGDs) can be a barrier to successful aided telephone calls. The timing of message delivery when using an SGD may vary depending on the type of access method used. We measured the difference in the success rate of telephone calls made with an SGD either using switch scanning or direct selection with eye gaze. The scripted calls, asking for directions, were placed to 100 randomly selected businesses. Analysis showed a statistically significant difference in the success rate between the two conditions, with eye gaze access resulting in more successful calls. Findings from this study suggest that people who use SGDs for phone calls may improve the timing of message delivery by using eye gaze access compared to switch scanning. PMID- 27400282 TI - Cystatin C-Creatinine Based Glomerular Filtration Rate Equation in Obese Chronic Kidney Disease Patients: Impact of Deindexation and Gender. AB - BACKGROUND: Cystatin C is considered an alternative to creatinine to estimate glomerular filtration rate (GFR). However, studies have reported that increased adiposity is associated with a higher level of circulating cystatin C questioning the performance of estimation of GFR using cystatin C in obese subjects. METHODS: We prospectively included 166 obese stages 1-5 chronic kidney disease (CKD) patients between 2013 and 2015. GFR was measured with a reference method without (measured GFR [mGFR]) and with adjustment to body surface area (mGFRr) and estimated (eGFR) or de-indexed eGFR using the Chronic Kidney Disease and Epidemiology (CKD-EPI) equation using creatinine (CKD-EPIcreat), cystatin (CKD EPIcyst) and the combination of cystatin and creatinine (CKD-EPIcyst-creat). RESULTS: The biases between mGFR and de-indexed CKD-EPIcyst-creat were significantly lower than de-indexed CKD-EPIcreat (p = 0.001). Accuracies were significantly better with de-indexed CKD-EPIcyst-creat compared to CKD-EPIcreat and CKD-EPIcyst, respectively (p = 0.04 and 0.03). Bland and Altman plot showed a great dispersion of all formulae when patients had a GFR >60 ml/min. Interestingly, there is a gender difference; biases, precisions and accuracies of de-indexed CKD-EPIcyst-creat were significantly lower in obese women. These results may be related to a difference in the change of body composition during obesity in men versus women and in fact only waist circumference (WC) was positively and significantly correlated with cystatin C (p < 0.0001) whereas body mass index (BMI; p = 0.3) was not; bias for CKD-EPIcyst-creat was related with WC. CONCLUSION: Cystatin C-creatinine-based GFR equations outperform creatinine based formula in obese CKD patients especially those with BMI >=35 and in obese women. PMID- 27400283 TI - Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach. AB - INTRODUCTION: In recent years, a variety of new synthetic methodologies and concepts have been proposed in the search for new pharmaceutical lead structures and optimization. Notably, the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry approach has drawn great attention and has become a powerful tool for the generation of privileged medicinal skeletons in the discovery of anti-HIV agents. This is due to the high degree of reliability, complete specificity (chemoselectivity and regioselectivity), mild conditions, and the biocompatibility of the reactants. AREAS COVERED: Herein, the authors describe the progress thus far on the discovery of novel anti-HIV agents via the CuAAC click chemistry-based approach. EXPERT OPINION: CuAAC click chemistry is a proven protocol for synthesizing triazole products which could serve as basic pharmacophores, act as replacements of traditional scaffold or substituent modification, be a linker of dual-target or dual-site inhibitors and more for the discovery of novel anti-HIV agents. What's more, it also provides convenience and feasibility for dynamic combinatorial chemistry and in situ screening. It is envisioned that click chemistry will draw more attention and make more contributions in anti-HIV drug discovery in the future. PMID- 27400285 TI - A Single Session of Autogenic Training Increases Acute Subjective and Physiological Sexual Arousal in Sexually Functional Women. AB - Heart rate variability (HRV) has recently been associated with female sexual function (Stanton, Lorenz, Pulverman, & Meston, 2015). Below-average HRV was identified as a possible risk factor for sexual arousal dysfunction and overall sexual dysfunction in women. Based on this newly established relationship between HRV and female sexual function, the present study examined the effect of autogenic training to increase HRV on acute physiological and subjective sexual arousal in women. Specifically, vaginal pulse amplitude (VPA), an index of genital sexual arousal, and subjective sexual arousal were assessed in 33 sexually functional women, aged 18 to 27, before and after a short session of autogenic training. Autogenic training, a relaxation technique that restores the balance between the activity of the sympathetic and the parasympathetic branches of the autonomic nervous system, has been shown to significantly increase HRV (Miu, Heilman, & Miclea, 2009). After autogenic training, significant increases in both VPA (p <.05) and subjective sexual arousal (p <.005) were observed. Moreover, change in HRV from pre- to postmanipulation significantly moderated changes in subjective sexual arousal (p <.05) when it was measured continuously during the presentation of the erotic stimulus. This cost-effective, easy-to administer behavioral intervention may have important implications for increasing sexual arousal in women. PMID- 27400287 TI - Correction: Socially selected ornaments and fitness: Signals of fighting ability in paper wasps are positively associated with survival, reproductive success, and rank. PMID- 27400286 TI - Transparency and reproducibility in evolutionary research. PMID- 27400288 TI - Bottom-Up Construction of a CO2-Based Cycle for the Photocarbonylation of Benzene, Promoted by a Rhodium(I) Pincer Complex. AB - The use of carbon dioxide for synthetic applications presents a major goal in modern homogeneous catalysis. Rhodium-hydride PNP pincer complex 1 is shown to add CO2 in two disparate pathways: one is the expected insertion of CO2 into the metal-hydride bond, and the other leads to reductive cleavage of CO2, involving metal-ligand cooperation. The resultant rhodium-carbonyl complex was found to be photoactive, enabling the activation of benzene and formation of a new benzoyl complex. Organometallic intermediate species were observed and characterized by NMR spectroscopy and X-ray crystallography. Based on the series of individual transformations, a sequence for the photocarbonylation of benzene using CO2 as the feedstock was constructed and demonstrated for the production of benzaldehyde from benzene. PMID- 27400289 TI - Emergence and maintenance of excitability: kinetics over structure. AB - The capacity to generate action potentials in neurons and other excitable cells requires tuning of both ionic channel expression and kinetics in a large parameter space. Alongside studies that extend traditional focus on control-based regulation of structural parameters (channel densities), there is a budding interest in self-organization of kinetic parameters. In this picture, ionic channels are continually forced by activity in-and-out of a pool of states not available for the mechanism of excitability. The process, acting on expressed structure, provides a bed for generation of a spectrum of excitability modes. Driven by microscopic fluctuations over a broad range of temporal scales, self organization of kinetic parameters enriches the concepts and tools used in the study of development of excitability. PMID- 27400290 TI - When brain rhythms aren't 'rhythmic': implication for their mechanisms and meaning. AB - Rhythms are a prominent signature of brain activity. Their expression is correlated with numerous examples of healthy information processing and their fluctuations are a marker of disease states. Yet, their causal or epiphenomenal role in brain function is still highly debated. We review recent studies showing brain rhythms are not always 'rhythmic', by which we mean representative of repeated cycles of activity. Rather, high power and continuous rhythms in averaged signals can represent brief transient events on single trials whose density accumulates in the average. We also review evidence showing time-domain signals with vastly different waveforms can exhibit identical spectral-domain frequency and power. Further, non-oscillatory waveform feature can create spurious high spectral power. Knowledge of these possibilities is essential when interpreting rhythms and is easily missed without considering pre-processed data. Lastly, we discuss how these findings suggest new directions to pursue in our quest to discover the mechanism and meaning of brain rhythms. PMID- 27400291 TI - Delayed heart rate recovery after exercise as a risk factor of incident type 2 diabetes mellitus after adjusting for glycometabolic parameters in men. AB - BACKGROUND: Some studies have reported that delayed heart rate recovery (HRR) after exercise is associated with incident type 2 diabetes mellitus (T2DM). This study aimed to investigate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the development of T2DM including glucose-associated parameters as an adjusting factor in healthy Korean men. MATERIAL AND METHODS: Analyses including fasting plasma glucose, HOMA-IR, HOMA beta, and HbA1c as confounding factors and known confounders were performed. HRR was calculated as peak heart rate minus heart rate after a 1-min rest (HRR 1). Cox proportional hazards model was used to quantify the independent association between HRR and incident T2DM. RESULTS: During 9082 person-years of follow-up between 2006 and 2012, there were 180 (10.1%) incident cases of T2DM. After adjustment for age, BMI, systolic BP, diastolic BP, smoking status, peak heart rate, peak oxygen uptake, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, HOMA beta, and HbA1c, the hazard ratios (HRs) [95% confidence interval (CI)] of incident T2DM comparing the second and third tertiles to the first tertile of HRR 1 were 0.867 (0.609-1.235) and 0.624 (0.426-0.915), respectively (p for trend=0.017). As a continuous variable, in the fully-adjusted model, the HR (95% CI) of incident T2DM associated with each 1 beat increase in HRR 1 was 0.980 (0.960-1.000) (p=0.048). CONCLUSIONS: This study demonstrated that delayed HRR after exercise predicts incident T2DM in men, even after adjusting for fasting glucose, HOMA-IR, HOMA-beta, and HbA1c. However, only HRR 1 had clinical significance. PMID- 27400292 TI - Intimal disruption affects drug-eluting cobalt-chromium stent expansion: A randomized trial comparing scoring and conventional balloon predilation. AB - BACKGROUND: Stent expansion remains one of the most important predictors of restenosis and subacute thrombosis, even with the use of drug-eluting stents. This study was designed to clarify the impact of lesion preparation on final stent expansion. METHODS: Sixty-six consecutive patients were included in this trial, and ultimately 52 enrolled non-calcified de novo lesions were randomly assigned to undergo single predilation with either a semi-compliant scoring balloon or a semi-compliant conventional balloon. Lesions were treated with a single 2.5- to 3.0-mm cobalt-chromium everolimus-eluting stent under optical coherence tomography (OCT) guidance without post-stenting dilation. Stent expansion was defined as the ratio of OCT-measured minimum stent area to the predicted stent area. RESULTS: Stent expansion was significantly higher after predilation by a scoring balloon (68.0% vs. 62.1%, p=0.017) with similar stent lumen eccentricity (0.84 vs. 0.80, p=0.18). Intimal disruption was induced significantly more frequently (68.0% vs. 38.4%, p=0.035) and was more extensive in the scoring group (122 degrees vs. 65 degrees , p=0.038). Lesions with intimal disruption after predilation achieved significantly higher stent expansion than that without it (67.7% vs. 61.6%, p=0.023). One case in the conventional group required target lesion revascularization; however, any other adverse clinical events including death, myocardial infarction, and stent thrombosis were not observed up to 9months after PCI in both groups. CONCLUSIONS: In this randomized study, pretreatment with a scoring balloon enhanced stent expansion partly through induction of intimal disruption. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014176. PMID- 27400293 TI - Optical coherence tomography guided treatment of recurrent drug-eluting stent failure using drug-eluting balloon. PMID- 27400294 TI - Remote ischemic preconditioning in patients undergoing cardiovascular surgery: Evidence from a meta-analysis of randomized controlled trials. AB - BACKGROUND: Remote ischemic preconditioning (RIPC) has been associated with reduced risk of myocardial injury in patients undergoing cardiovascular surgery, but uncertainty about clinical outcomes remains, particularly in the light of 2 recent large randomized clinical trials (RCTs) which were neutral. We performed a meta-analysis to evaluate the efficacy of RIPC on clinically relevant outcomes in patients undergoing cardiovascular surgery. METHODS: We searched PubMed, Cochrane CENTRAL, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through November 30, 2015. RCTs that compared the effects of RIPC vs. control in patients undergoing cardiac and/or vascular surgery were selected. We calculated summary random-effect odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: The analysis included 5652 patients from 27 RCTs. RIPC reduced the risk of myocardial infarction (MI) (OR 0.72, 95% CI, 0.52 to 1.00; p=0.05; number needed to treat (NNT)=42), acute renal failure (OR 0.73, 95% CI, 0.53 to 1.00; p=0.05; NNT=44) as well as the composite of all cause mortality, MI, stroke or acute renal failure (OR 0.60, 95% CI, 0.39 to 0.90; p=0.01; NNT=25). No significant difference between RIPC and the control groups was observed for the outcome of all-cause mortality (OR 1.10, 95% CI, 0.81 to 1.51). Randomization to RIPC group was also associated with significantly shorter hospital stay (weighted mean difference -0.15days; 95% CI -0.27 to -0.03days). CONCLUSIONS: RIPC did not decrease overall mortality, but was associated with less MI and acute renal failure and shorter hospitalizations in patients undergoing cardiac or vascular surgery. PMID- 27400295 TI - Clinicodemographic features and outcome of acute myocarditis in children admitted at tertiary care hospital. AB - BACKGROUND: Myocarditis is an inflammatory disorder of myocardium associated with high mortality and morbidity. It is often difficult to diagnose because it can either be asymptomatic or mimic other illnesses. This study is conducted to evaluate clinicodemographic features and outcome of acute myocarditis in children admitted at a tertiary care hospital. METHODS: Medical records of all children aged 1month to 16years who were admitted between 2005 and 2013 at Aga Khan University Hospital, Karachi and discharged with a diagnosis of myocarditis were reviewed retrospectively. Clinical and demographic features, management and outcome were recorded. RESULTS: Records of a total of 62 patients with the diagnosis of myocarditis were reviewed retrospectively between 2005 and 2013. Median age of patients was 12.5months with 28 (45%) females and 34 (55%) males. The main presenting complaint observed was irritability (73%) and least common symptom was abdominal pain (23%) while the most frequently occurring examination finding was tachycardia (90%). Length of the hospital stay was 8+/-4.7days with 21 (34%) admissions in the ward and 41 (66%) in intensive care unit. CONCLUSION: The most frequent presentation in our study was irritability, followed by difficulty in breathing while the least common symptom was abdominal pain. Tachycardia was the commonest clinical sign observed so it is important to look for heart rate and rhythm in a sick child with irritability. PMID- 27400296 TI - Impact of paravalvular aortic regurgitation after transcatheter aortic valve implantation on survival. AB - OBJECTIVES: To determine whether >=moderate paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) independently impairs overall survival and how much the impact on survival is, we performed an updated meta-analysis pooling not unadjusted but adjusted hazard ratios (HRs). METHODS: Databases including MEDLINE and EMBASE were searched through January 2016 using PubMed and OVID. Search terms included paravalvular or perivalvular; regurgitation, leak, or leakage; percutaneous, transcatheter, transluminal, transarterial, transapical, transaortic, transcarotid, transaxillary, transsubclavian, transiliac, transfemoral, or transiliofemoral; and aortic valve. Studies considered for inclusion met the following criteria: the design was an observational comparative study; the study population was patients undergoing TAVI; patients were divided into >=moderate and <=mild post-TAVI PAR; outcomes included >=1-year all-cause mortality; and the adjustment method was a multivariate Cox proportional hazards analysis. An adjusted HR with its 95% confidence interval (CI) for >=moderate post-TAVI PAR was abstracted from each individual study. RESULTS: Our search identified 17 eligible studies including a total of 15,131 patients. A pooled analysis of all the 17 studies demonstrated a statistically significant 2.12-fold increase in mortality with >=moderate PAR (HR, 2.12; 95% CI, 1.79 to 2.51; p<0.00001). Exclusion of any single study from the meta-analysis did not substantively alter the overall result disfavoring >=moderate PAR. Although the statistical tests suggested funnel plot asymmetry, the corrected effect estimate from the trim-and-fill method demonstrated still a statistically significant 1.83-fold risk of mortality with >=moderate PAR. CONCLUSIONS: >=Moderate post-TAVI PAR is associated with a 2.12-fold increase in overall (>=1-year) all-cause mortality. PMID- 27400297 TI - Addition of TGF-beta1 to existing clinical risk scores does not improve prediction for arrhythmia recurrences after catheter ablation of atrial fibrillation. PMID- 27400298 TI - Should doctors still examine patients? AB - The physical examination skills of young physicians in training need careful examination as advancing technology seems to have replaced those skills compared to prior generations of physicians. A question to ponder is how should medical education address the convincing evidence that physician trainees of today are less astute at the physical examination than those that came before them? This inquiry must address whether the decline in physical examination skills hinders accurate, cost effective, and timely diagnoses. Additionally, it must consider whether the absence of a comprehensive physical examination impairs the patient physician relationship. This type of inquiry leads to the conclusion that the physical examination and technology must be merged as the clinical situation dictates to provide accurate, cost effective and accurate diagnoses. The carefully performed physical examination in conjunction with a detailed history should dictate the use of our ever-advancing technologic advances in medicine. PMID- 27400299 TI - Ticagrelor for left ventricular assist device thrombosis: A new therapeutic option to be evaluated with caution. PMID- 27400300 TI - What is the optimal length of stay in hospital after primary PCI. PMID- 27400301 TI - Arterial stiffness is strongly and negatively associated with the total volume of red blood cells. AB - BACKGROUND: Erythropoiesis is partly regulated through classic feedback pathways that govern blood volume (BV) as sensed by veno-atrial but also arterial stretch receptors. Hence, the total volume of red blood cells (RBCV) could be associated with arterial stiffness (AS), although such hypothesis has not yet been tested. Therefore, we sought to investigate the association of AS with hematological variables including RBCV. METHODS: Fourteen healthy physically active individuals volunteered for the study (age=23+/-2). RBCV, plasma volume (PV), and BV were calculated from measures of hematocrit and total hemoglobin mass (Hbmass) determined by CO-rebreathing. Carotid compliance with ultrasonography and carotid ankle pulse wave velocity (PWV) were determined at rest and immediately after a maximal exercise test. The rationale for assessment of AS after exercise derives from the potential marked role of AS in the regulation of erythropoiesis in the setting of reduced central venous pressure. RESULTS: At rest, carotid compliance was positively associated with Hbmass, RBCV, BV, but not PV, with coefficients of determination (R(2)) ranging from 0.39 to 0.57. Following exercise, closer positive associations were observed between carotid compliance and Hbmass, RBCV, or BV. Moreover, carotid-ankle PWV was negatively associated with all hematological variables after exercise except for PV, with R(2) ranging from 0.49 to 0.75. Similar results were observed when adjusted by body weight. CONCLUSIONS: AS is strongly and inversely associated with RBCV in healthy individuals. These findings suggest that AS may adversely intercede in the regulation of erythropoiesis through the alteration of mechanisms that control BV. PMID- 27400302 TI - Do we need to monitor the percentage of biventricular pacing day by day? AB - BACKGROUND: Incidence and clinical significance of transient, daily fluctuations of biventricular pacing percentage (CRT%) remain unknown. We assessed the value of daily remote monitoring in identifying prognostically critical burden of low CRT%. METHODS AND RESULTS: Prospective, single-centre registry encompassed 304 consecutive heart failure patients with cardiac resynchronization therapy defibrillators (CRT-D). Patients with 24-h episodes of CRT% loss<95% were assigned to quartiles depending on cumulative time spent in low CRT%: quartile 1 (1-8days), 2 (9-20days), 3 (21-60days) and quartile 4 (>60days). During median follow-up of 35months 51,826 transmissions were analysed, including 15,029 in 208 (68.4%) patients with episodes of low CRT%. Overall, mean CRT%>=95% vs. <95% resulted in a 4-fold lower mortality (17.3 vs. 68.2%; p<0.001). Fifty-four percent of patients experienced episodes of CRT% loss, despite 85.6% having mean CRT%>=95%. Mortality was lowest in quartile 1 (7.7%), while longer periods of CRT% loss resulted in significantly higher death rates (25.0 vs. 34.6 vs. 57.7%; quartiles 2-4 respectively, p<0.001), despite mean CRT% still being >=95% in quartiles 1-3. Cumulative low CRT% burden was the independent risk factor for death (HR 1.013; 95% CI 1.006-1.021; p<0.001). Mortality rose by 1.3 and 49% with every additional day and quartile of CRT% loss, respectively. CONCLUSIONS: Daily remote monitoring allows one to detect 24-h episodes of CRT% loss<95% in over two thirds of CRT-D recipients during median observation of 3years. Cumulative low CRT% burden (in days) independently predicts mortality before mean CRT% drop. PMID- 27400303 TI - Different prognostic factors according to left ventricular systolic function in patients with acute myocardial infarction. AB - BACKGROUND: Initial left ventricular (LV) systolic function is a main determinant of clinical outcomes in patients with acute myocardial infarction (AMI). This study was performed to investigate whether AMI patients have different prognostic factors according to their baseline LV systolic function. METHODS: A total of 12,988 patients with AMI from a nationwide database were analyzed. Major adverse cardiovascular events (MACEs) within 12months of AMI, including death, nonfatal myocardial infarction (MI), and revascularization, were assessed. RESULTS: Patients were stratified into two groups according to LV ejection fraction (LVEF): those with LVEF<40% and those with LVEF>=40%. Patients with LVEF<40% (n=1962, 15.1%) were older and had more unfavorable cardiovascular risk factors than those with LVEF>=40% (n=11,026, 84.9%). The rate of MACE was higher in patients with LVEF<40% than in those with LVEF>=40% (26.8% vs 11.4%, p<0.001). Independent predictors of 12-month MACEs in patients with LVEF>=40% were history of MI, high Killip stage, three-vessel disease, and lower renal function, which are already known as risk factors. However, diabetes mellitus (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.17-2.40; p=0.008), and the use of rennin angiotensin system (RAS) blockers (HR, 0.63; 95% CI, 0.41-0.95; p=0.029) were independent factors for 12-month MACE in patients with LVEF <40%. CONCLUSIONS: Prognostic factors determining 12-month MACE after AMI are different according to LVEF. Management following AMI should be tailored according to their LV systolic function. PMID- 27400304 TI - Silent cerebral injury after transcatheter aortic valve implantation and the preventive role of embolic protection devices: A systematic review and meta analysis. AB - BACKGROUND: The aims of this study were: 1) to evaluate silent cerebral injury detected by cerebral diffusion weighted magnetic resonance imaging (DW-MRI) after transcatheter aortic valve implantation (TAVI); and 2) to assess the efficacy of embolic protection devices (EPDs) on DW-MRI endpoints. METHODS: We included in a pooled analysis 25 prospective studies reporting post-procedural cerebral DW-MRI data after TAVI (n=1225). Among these studies, we included in a meta-analysis 6 studies investigating TAVI performed with versus without EPDs (n=384). Primary endpoints were the number of new lesions per patient and the total lesion volume, while secondary endpoints were the number of patients with new lesions and the single lesion volume. RESULTS: The main pooled DW-MRI outcomes were: patients with new ischemic lesions, 77.5% (95% confidence interval=71.7-83.3%); total lesion volume, 437.5mm(3) (286.7-588.3mm(3)); single lesion volume, 78.1mm(3) (56.7-99.5mm(3)); and number of new lesions per patient, 4.2 (3.4-5.0). The use of EPDs was associated with a significant reduction in total lesion volume (mean difference [95% confidence interval]=-111.1mm(3) [-203.6 to -18.6mm(3)]; p=0.02) and single lesion volume (-12.1mm(3) [-18.3 to -6.0mm(3)]; p=0.0001) after TAVI. CONCLUSIONS: Silent cerebral injury occurs in the majority of patients undergoing TAVI and DW-MRI allows a precise characterization of new ischemic brain lesions. EPDs reduce the total and single volume of such lesions detected after the procedure, although the number of new lesions per patient and the number of patients with new lesions are not significantly reduced by such devices. PMID- 27400306 TI - Has Saint Anthony of Padua suffered from congestive heart failure? PMID- 27400305 TI - Surgical management of giant coronary aneurysms in Noonan syndrome. PMID- 27400307 TI - To treat the patient and not the telemetry: Electric toothbrush causing hospital admission. PMID- 27400308 TI - Sildenafil reduces pulmonary vascular resistance in single ventricular physiology. AB - BACKGROUND: High pulmonary vascular resistance (PVR) may be a risk factor for early and late mortality in both Glen shunt and Fontan operation patients. Furthermore, PVR may increase long after the Fontan operation. Whether pulmonary vasodilators such as phosphodiesterase 5 inhibitors can decrease PVR in patients with single ventricular physiology remains undetermined. METHODS AND RESULTS: This was a prospective, multicenter study. Patients with single ventricular physiology who have a PVR index higher than 2.5 Wood units.? (WU) were enrolled. Cardiac catheterization was performed before and after administration of sildenafil in all patients. After the Fontan operation, a six minute walk test (6MWT) was also performed. A total of 42 patients were enrolled. PVR was significantly decreased in each stage of single ventricular physiology after sildenafil administration: from 4.3+/-1.5WU to 2.1+/-0.6WU (p<0.01) in patients before a Glenn shunt, from 3.2+/-0.5WU to 1.6+/-0.6WU (p<0.001) in patients after a Glenn shunt, and from 3.9+/-1.7WU to 2.3+/-0.8WU (p<0.001) in patients after Fontan. In patients after Fontan, the 6MWT increased from 416+/-74m to 485+/-72m (p<0.01), and NYHA functional class improved significantly (p<0.05) after sildenafil administration. No major side effects were observed in any patients. CONCLUSIONS: Sildenafil reduced PVR in patients with single ventricle physiology. Sildenafil increased exercise capacity and improved NYHA functional class in patients after a Fontan operation. This implies that pulmonary vasodilation is a potential therapeutic target in selected patients with elevated PVR with single ventricle physiology. Long-term clinical significance warrants further study. PMID- 27400309 TI - Peripheral endothelial function may predict the effectiveness of beta-blocker therapy in patients with idiopathic dilated cardiomyopathy. AB - OBJECTIVES: Beta-blockers have improved the prognosis of patients with dilated cardiomyopathy as they improve left ventricular (LV) systolic function and structure, which are crucial for myocardial recovery. However, to date, no accurate methods can predict the effectiveness of beta-blocker therapy. Our goal was to evaluate whether peripheral endothelial function could be a useful predictor for beta-blocker responses and related LV reverse remodeling (LVRR) in patients with idiopathic dilated cardiomyopathy (IDC). METHODS: Fifty-two IDC patients were recruited and underwent brachial artery flow-mediated dilation (FMD). Beta-blockers were titrated to doses tolerable for each patient. LV function and structure were measured by echocardiography. A positive response to beta-blockers was defined as an increase of >=10% in LV ejection fraction (LVEF). LVRR was defined as an increase of >=10% in LVEF and a decrease of >=15% in LV end-systolic volume (LVESV). RESULTS: Baseline FMD was 8.4+/-3.0% in IDC patients and significantly lower than healthy controls. At three-month follow-up, 54% of patients had a positive beta-blocker response and 40% achieved LVRR. Patients with a positive response to beta-blockers or with LVRR had significantly higher baseline FMD values than those without. FMD was the most significant predictor of changes in LVEF and LVESV. The sensitivity and specificity of baseline FMD to predict beta-blocker responses was 64.3% and 83.3%, respectively, and to predict LVRR was 61.9% and 80.6%, respectively. Beta-blockers themselves did not influence FMD values. CONCLUSIONS: FMD could serve as an independent predictor for monitoring beta-blocker therapy effectiveness in IDC patients. PMID- 27400310 TI - Serum phosphorus is related to left ventricular remodeling independent of renal function in hospitalized patients with chronic kidney disease. AB - BACKGROUND: Increasing evidence indicated that phosphorus emerged as an important cardiovascular risk factor in patients with chronic kidney disease (CKD). The fact that serum phosphorus was closely linked to vascular and valvar calcification may account for one important reason. However, left ventricular remodeling may also serve as another potential mechanism of the cardiac toxicity of phosphorus. In the present study, we evaluated the association of serum phosphorus with left ventricular remodeling. METHODS: We investigated consecutive hospitalized patients with pre-dialysis CKD, who did not have symptomatic heart failure or take any phosphorus binder or calcitriol medications. Transthoracic echocardiography was applied to assess their left ventricular remodeling indices, both structural and functional. RESULTS: The 296 study subjects (mean age 56.4years) included 169 (57.1%) men, 203 (68.6%) hypertensive patients. In addition to gender, systolic blood pressure, and estimated glomerular filtration rate, serum phosphorus was an independent determinant of left ventricular mass index (LVMI, P=0.001). Similarly, serum phosphorus was also a determinant of left ventricular end diastolic dimension (P=0.0003), but not of relative wall thickness. In multivariate logistic analyses, serum phosphorus was significantly and independently associated with the prevalence of left ventricular hypertrophy (LVH, odds ratio [OR] 2.38 for each 1mmol/L increase, 95% CI 1.20-4.75, P=0.01). Moreover, the association was only confirmatory in eccentric LVH (OR 3.01, 95% CI 1.43-6.32, P=0.003) but not in concentric LVH (1.38, 95% CI, 0.54-3.49, P=0.50). CONCLUSION: Serum phosphorus was significantly and independently associated with LVMI and the prevalence of eccentric LVH in hospitalized patients with CKD. PMID- 27400311 TI - Incremental value of ePLAR - echocardiographic Pulmonary to Left Atrial Ratio - in the diagnosis of chronic thromboembolic pulmonary hypertension. PMID- 27400312 TI - Case load and valve surgery outcome in Australia. AB - BACKGROUND: In Australia it has been suggested that heart valve surgery, particularly for rheumatic heart disease (RHD), should be consolidated in higher volume centres. International studies of cardiac surgery suggest large volume centres have superior outcomes. However the effect of site and surgeon case load on longer term outcomes for valve surgery has not been investigated. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. The adjusted association between both average annual site and surgeon case load on short term complications and short and long term survival was determined. RESULTS: Outcomes associated with 20,116 valve procedures at 25 surgical sites and by 93 surgeons were analysed. Overall adjusted analysis showed increasing site and surgeon case load was associated with longer ventilation, less reoperation and more anticoagulant complications. Increasing surgeon case load was also associated with less acute kidney injury. Adjusted 30-day mortality was not associated with site or surgeon case load. There was no consistent relationship between increasing site case load and long term survival. The association between surgeon case load and outcome demonstrated poorer adjusted survival in the highest volume surgeon group. CONCLUSIONS: In this Australian study, the adjusted association between surgeon and site case load was not simple or consistent. Overall larger volume sites or surgeons did not have superior outcomes. Mandating a particular site case load level for valve surgery or a minimum number of procedures for individual surgeons, in an Australian context, cannot be supported by these findings. PMID- 27400314 TI - Noise enhanced the electrical stimulation-contractile response coupling in isolated mouse heart. AB - BACKGROUND: Stochastic resonance is a phenomenon that allows a system to improve its capability to detect stimulus when a limited amount of noise is added to the stimuli. It has experimentally been shown that noise enhances the homeostatic function of the blood pressure regulatory system. This study aimed to investigate whether the noise can enhance the contractile response in the whole heart. METHODS: Experiments were conducted in isolated mouse hearts (0.040kg, n=8), a Langendorff heart preparation is used to obtain two variables of the contractile response contraction force and heart rate. The contractile response due to an electrical stimulation perturbed with Gaussian noise was recorded. RESULTS: The results show that the intensity of noise induced in the electrical stimuli has an effect on the electrical stimulation-contractile response coupling. With 10% noise induced, the bandwidth where the synchronization effect is presented was increased from (7-11Hz) to (6-12Hz), and the irregular dynamic threshold was changed to 13Hz. CONCLUSIONS: We find that the noise increases the synchronization bandwidth in the electrical stimulation-contractile response coupling. We have experimentally demonstrated the stochastic resonance in isolated mouse heart. PMID- 27400313 TI - Demographic parameters related to 30-day readmission of patients with pulmonary embolism: Analysis of 650,819 hospitalizations. AB - BACKGROUND: Pulmonary embolism (PE) is a serious medical condition associated with major morbidity, mortality and economic burden. Preventable hospital readmissions are a major economic challenge for the healthcare organizations and identifying patient subsets at risk of readmission will help report the issue. This retrospective study was performed to determine demographic parameters and major diagnosis linked with 30day readmission after a PE. METHODS: Nationwide Inpatient Sample (NIS) data was used to extract data of patients discharged after PE during index admission for years 2009-2013. Patients were identified by Diagnosis Related Group (DRG) number 175 and 176 which represents PE with major complications and comorbidities (MCC) and PE without MCC. Demographic parameters associated with high readmission rate were identified along with causes related to readmissions. RESULTS: We identified a total of 650,819 hospitalizations with PE as the index stay DRG of which 13.44% were readmitted within 30 days after hospitalizations. Patients with age >65years (14.05%), female (13.87%), Medicaid insurances (20.49%), low median income for zip code (15.1%) and metropolitan areas (13.71%) were associated with higher 30day readmission rates. The most common identified cause of readmission in PE with MCC from 2009 to 2010 was heart failure (4.25%) and from 2011 to 2013 was severe sepsis (4.8%) while for PE without MCC from 2009 to 2013 was PE without MCC itself (10.24%). CONCLUSIONS: Interventions need to be directed against these set of patients and the identified causes of readmissions to reduce the rehospitalisations from PE. PMID- 27400315 TI - Clinical implications of low-dose aspirin on vasospastic angina patients without significant coronary artery stenosis; a propensity score-matched analysis. AB - BACKGROUND: High-dose aspirin has been reported to exacerbate coronary artery spasm in patients with vasospastic angina. We investigated clinical implications of low-dose aspirin on vasospastic angina patients without significant coronary artery stenosis. METHODS: We included patients without significant coronary artery stenosis on coronary angiography (CAG) and with positive results on intracoronary ergonovine provocation test between January 2003 and December 2014. A total of 777 patients were divided into two groups according to prescription of low-dose aspirin at discharge: aspirin group (n=321) and non-aspirin group (n=456). The major adverse cardiovascular events (MACE), defined as composite outcomes of cardiac death, acute myocardial infarction, revascularization, or rehospitalization requiring CAG or medication change due to recurrent angina were compared. RESULTS: The aspirin group had significantly higher incidence of MACE (22.8% versus 12.1%; p=0.04) and had higher tendency for rehospitalization (20.6% versus 11.2%; p=0.08). All-cause mortality and cardiac death were similar between the two groups. After propensity score matching, the aspirin group had greater risk of MACE (hazard ratio [HR] 1.54; 95% confidence interval [CI], 1.04-2.28; p=0.037) and rehospitalization requiring CAG (HR, 1.33; 95% CI, 1.13-4.20; p=0.03), and a higher tendency for rehospitalization (HR, 1.40; 95% CI, 0.94 2.09; p=0.12). CONCLUSION: In vasospastic angina without significant coronary artery stenosis, patients taking low-dose aspirin are at higher risk of MACE, driven primarily by tendency toward rehospitalization. Low-dose aspirin might be used with caution in vasospastic angina patients without significant coronary artery stenosis. PMID- 27400316 TI - Longitudinal BNP follow-up as a marker of treatment response in acute heart failure: Relationship with objective markers of decongestion. AB - INTRODUCTION: Results of studies that examined the value of B-type natriuretic peptide (BNP) reduction as a marker of decongestion have been inconsistent. We investigated whether longitudinal admission-to-discharge BNP reduction can be used to monitor decongestion during acute heart failure (HF). METHODS: We used the ESCAPE trial data to study the relationship between the magnitude of BNP reduction and various clinical and objective markers of decongestion. RESULTS: Admission-to-discharge reduction in BNP was recorded in 245 patients who were divided into tertiles (tertile 1 had BNP reduction<27pg/mL, tertile 2 had BNP reduction 27-334pg/mL and tertile 3 had BNP reduction>334pg/mL). There were significant differences across tertiles with regard to resolution of jugular venous distension (JVD, P=0.014) and orthopnea (P=0.04) on discharge, admission to-discharge weight loss (P=0.002), and admission-to-discharge reduction in inferior vena cava (IVC) diameter (P=0.0001). Compared with the first tertile, patients in the third tertile had significantly higher frequency of resolution of JVD (univariate OR 2.657, P=0.004) and orthopnea (univariate OR 2.083, P=0.032) on discharge, more weight loss (P=0.001), higher IVC diameter reduction (P<0.0001), and higher reduction in pulmonary capillary wedge pressure (PCWP) from admission to day of PAC removal compared with first tertile (P<0.0001). Using the whole cohort, we found a significant correlation between admission-to discharge BNP reduction and admission-to-discharge weight loss (n=232, r=0.211, P=0.001), admission-to-discharge reduction in IVC diameter (n=99, r=0.360, P<0.0001) and reduction in PCWP from admission to the day of pulmonary artery catheter removal (n=92, r=0.242, P=0.02). CONCLUSION: Admission-to-discharge BNP reduction is a reasonable marker of treatment response in HF that correlated with clinical and objective markers of decongestion. PMID- 27400317 TI - Over-expansion capacity and stent design model: An update with contemporary DES platforms. AB - BACKGROUND: Previously, we examined the difference in stent designs across different sizes for six widely used Drug Eluting Stents (DESs). Although stent post-dilatation to larger diameter is commonly done, typically in the setting of long tapering segment or left-main PCI, there is an increasing recognition that information with regard to the different stent model designs has a critical impact on overexpansion results. This study aims to provide an update on stent model designs for contemporary DES platforms as well as test overexpansion results under with oversized post-dilatation. METHODS AND RESULTS: We studied 6 different contemporary commercially available DES platforms: Synergy, Xience Xpedition, Ultimaster, Orsiro, Resolute Onyx and Biomatrix Alpha. We investigated for each platform the difference in stent designs across different sizes and results obtained after post-expansion with larger balloon sizes. The stents were deployed at nominal diameter and subsequently over expanded using increasingly large post dilatation balloon sizes (4.0, 5.0 and 6.0mm at 14ATM). Light microscopy was used to measure the changes in stent geometry and lumen diameter after over-expansion. For each respective DES platform, the MLD observed after overexpansion of the largest stent size available with a 6.0mm balloon was 5.7mm for Synergy, 5.6mm for Xience, 5.2mm for Orsiro, 5.8mm for Ultimaster, 5.5mm for 4mm Onyx (5.9mm for the 5mm XL size) and 5.8mm for BioMatrix Chroma. CONCLUSION: This update presents valuable novel insights that may be helpful for careful selection of stent size for contemporary DES based on model designs. Such information is especially critical in left main bifurcation stenosis treatment where overexpansion to larger oversized diameter may be required to ensure full stent apposition. PMID- 27400318 TI - Detection of transmissible viral proventriculitis and chicken proventricular necrosis virus in the UK. AB - Increasing evidence suggests that a new birnavirus, named chicken proventricular necrosis virus (CPNV), is the aetiological agent of transmissible viral proventriculitis (TVP). The present work aimed to explore the possible presence of both TVP and CPNV in the UK. Forty-four chickens showing TVP-compatible gross lesions were classified into three groups based on the histological lesions: (i) TVP-affected chickens: lymphocytic infiltration and glandular necrosis (n = 15); (ii) lymphocytic proventriculitis (LP)-affected chickens: lymphocytic infiltration without necrosis (n = 18); and (iii) without proventriculitis (WP): no lymphocytic infiltration or necrosis (n = 11). Nine proventriculi (seven out of 15 corresponding to TVP, and two out of 11 corresponding to LP) were positive for CPNV by reverse transcriptase polymerase chain reaction (RT-PCR). These results support the previously suggested idea of CPNV as causative agent of TVP. Moreover, these data show that CPNV can also be detected in a number of cases with LP, which do not fulfil the histological TVP criteria. Phylogenetic analysis of partial sequences of gene VP1 showed that British CPNV sequences were closer to other European CPNV sequences and might constitute a different lineage from the American CPNV. TVP cases with negative CPNV PCR results may be due to chronic stages of the disease or to the reduced PCR sensitivity on formalin-fixed paraffin-embedded tissues. However, involvement of other agents in some of the cases cannot totally be ruled out. As far as the authors are aware, this is the first peer-reviewed report of TVP as well as of CPNV in the UK, and the first exploratory CPNV phylogenetic study. PMID- 27400319 TI - Incidence and Risk Factors of Lower Extremity Lymphedema After Gynecologic Surgery in Ovarian Cancer. AB - OBJECTIVE: There is no standard method to establish an early diagnosis of lower extremity lymphedema (LEL). Lower extremity lymphedema can be diagnosed by physical examination and laboratory tests when patients complain of typical clinical symptoms. The objective of this study was to investigate the incidence and risk factors of LEL in patients with ovarian cancer. METHODS: The medical records were reviewed retrospectively in patients with ovarian cancer treated at Seoul St. Mary's Hospital from January 2000 to July 2014. RESULTS: A total of 413 patients with epithelial ovarian cancer were analyzed. Forty-six patients (11.1%) developed LEL, and 67.4% of these patients had LEL within 1 year after surgery. The mean number of resected lymph nodes (LNs) was larger in patients with LEL (43.1 +/- 16.7; range, 12-80) than in those without (32.3 +/- 19.8; range, 0-99) (P < 0.0001). The number of resected LNs was significantly associated with the occurrence of LEL (odds ratio, 1.025; 95% confidence interval, 1.005-1.045; P < 0.05). CONCLUSION: A significant proportion of patients with ovarian cancer could develop LEL after surgery. This study suggests that the occurrence of LEL is associated with the number of resected LNs. PMID- 27400320 TI - Laparoscopically Assisted Radical Vaginal Hysterectomy for Early-Stage Cervical Cancer: A Systemic Review and Meta-Analysis. AB - OBJECTIVE: The aim of this study was to compare intraoperative and short-term postoperative outcomes and recurrence of laparoscopically assisted radical vaginal hysterectomy (LARVH) to abdominal radical hysterectomy (ARH) in the treatment of early-stage cervical cancer. METHODS: A search of PubMed, EMBASE, and Cochrane library search trial (central) databases was conducted from database inception through December 2015. We included studies comparing surgical approaches with radical hysterectomy (LARVH vs ARH) in women with stages IA1 to IIB cervical cancer. Outcomes included blood loss, operative time, number of lymph nodes retrieved, intraoperative complications, hospital stay, and prognosis. RESULT: Seven studies were included (4 prospective cohort studies and 3 case control studies) enrolling 794 women; 349 women were treated by LARVH, and 445 were treated by ARH. Laparoscopically assisted radical vaginal hysterectomy was associated with less blood loss (weight mean difference [WMD], -237.45; 95% confidence interval [CI], -453.42 to -21.47), wound-related complications (odds ratio, 0.17; 95% CI, 0.05-0.61), shorter hospital stay (WMD, -2.01; 95% CI, -2.52 to -1.51), and longer operative time (WMD, 48.95; 95% CI, 42.08 to 55.82) versus ARH. Laparoscopically assisted radical vaginal hysterectomy was comparable with ARH in number of lymph nodes retrieved, urinary-related complications, rectal injury, lymphedema, and all prognosis indicators. CONCLUSIONS: The evidence suggests that LARVH is superior to ARH with lower blood loss, less wound-related complications, and shorter hospital stay. Laparoscopically assisted radical vaginal hysterectomy and ARH seem equivalent in number of lymph nodes retrieved, urinary-related complications, rectal injury, lymphedema, and prognosis. PMID- 27400321 TI - The Prognosis and Risk Stratification Based on Pelvic Lymph Node Characteristics in Patients With Locally Advanced Cervical Squamous Cell Carcinoma Treated With Concurrent Chemoradiotherapy. AB - BACKGROUND: The purpose of this study is to determine the prognostic significance of pelvic lymph node (PLN) characteristics and perform risk stratification in patients undergoing concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma. METHODS: We retrospectively reviewed the records of 609 patients with Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage II to IVa who underwent concurrent chemoradiotherapy, compared overall survival (OS), distant metastasis-free survival (DMFS), and pelvic recurrence free survival between patients with or without PLN involvement. We further analyzed prognostic factors for OS and DMFS including FIGO stage, tumor volume, and lymph node (LN) characteristics in 300 patients with PLN involvement. RESULTS: The 3-year OS rate was 81.7% versus 92.8% (P = 0.002) and the 3-year DMFS rate was 79.3% versus 92.7% (P = 0.006) in patients with or without PLN involvement, respectively. With univariable analysis, FIGO stage, LN-volume, LN number, LN-diameter, and matted/necrotic LN affected both OS and DMFS. Based on multivariable analysis, we created a risk stratification model. For OS, the independent risk factors were FIGO stage III or IVa, LN-volume of 3 cm or more, LN-diameter of 1.5 cm or more, and matted/necrotic LN. The low-risk group (no risk factors), mid-risk group (1 or 2 risk factors), and high-risk group (3 or 4 risk factors) had a 3-year OS of 96.6%, 84.9%, and 64.7%, respectively (P = 0.005). For DMFS, LN-diameter of 1.5 cm or more, LN-number of 3 or more, and matted/necrotic LN were the independent risk factors. The subgroups for DMFS were the low-risk group (no risk factors), the mid-risk group (1 risk factor), and the high-risk group (2 or 3 risk factors), and the 3-year DMFS was 92.4%, 76.2%, and 64.6%, respectively (P = 0.001). CONCLUSIONS: The prognosis was significantly poorer for patients with high-risk lymph node characteristics. Using this risk stratification, we should select the most appropriate and individualized treatment modality to improve outcomes in those patients with a poorer prognosis. PMID- 27400323 TI - The association between environmental and psychosocial factors towards physical activity and screen time of children: an application of the Integrative Behavioural Model. AB - Physical activity is beneficial at all stages of life, and has been linked as a protective factor from obesity, and other chronic health conditions. Despite the benefits of physical activity, less than half of US children meet the current recommendations, and activity levels decline with age. When planning physical activity interventions, behavioural theories should be utilised, given the inherent benefits theory-based approaches possess. The purpose of this study was to investigate how constructs of the Integrative Theoretical Model (IM) are associated with physical activity and screen time among children (9 years +/-1.2; n = 264). Using structural equation modeling, a final model proved to have a good fit (CFI = 0.989; TLI = 0.975; RMSEA = 0.043), and results indicated intentions and perceived behavioural control (PBC) explained 19.4% of the variance for physical activity, and attitudes, perceived norms, and PBC accounted for 62% of the variance of intentions. Furthermore, attitudes and perceived norms were negatively associated with total screen time, and accounted for 10% of the variance. Results suggest that IM is a useful framework for explaining physical activity and screen time among children. PMID- 27400324 TI - A computational study on the N-heterocyclic carbene-catalyzed Csp(2)-Csp(3) bond activation/[4+2] cycloaddition cascade reaction of cyclobutenones with imines: a new application of the conservation principle of molecular orbital symmetry. AB - A comprehensive density functional theory (DFT) investigation has been performed to interrogate the mechanisms and stereoselectivities of the Csp(2)-Csp(3) single bond activation of cyclobutenones and their [4+2] cycloaddition reaction with imines via N-heterocyclic carbene (NHC) organocatalysis. According to our calculated results, the fundamental reaction pathway contains four steps: nucleophilic addition of NHC to cyclobutenone, C-C bond cleavage for the formation of an enolate intermediate, [4+2] cycloaddition of the enolate intermediate with isatin imine, and the elimination of the NHC catalyst. In addition, the calculated results also reveal that the second reaction step is the rate-determining step, whereas the third step is the regio- and stereo selectivity determining step. For the regio- and stereo-selectivity determining step, all four possible attack modes were considered. The addition of the C[double bond, length as m-dash]N bond in isatin imine to the dienolate intermediate is more energy favorable than the addition of the C[double bond, length as m-dash]O bond to a dienolate intermediate. Moreover, the Re face addition of the C[double bond, length as m-dash]N bond in isatin imine to the Re face of the dienolate intermediate leading to the SS configuration N-containing product was demonstrated to be most energy favorable, which is mainly due to the stronger second-order perturbation energy value in the corresponding transition state. Furthermore, by tracking the frontier molecular orbital (FMO) changes in the rate-determining C-C bond cleavage step, we found that the reaction obeys the conservation principle of molecular orbital symmetry. We believe that the present work would provide valuable insights into this kind of reaction. PMID- 27400322 TI - Proportions of blood-borne Vdelta1+ and Vdelta2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab. AB - Human gammadelta T-cells possess regulatory and cytotoxic capabilities, and could potentially influence the efficacy of immunotherapies. We analysed the frequencies of peripheral gammadelta T-cells, including their most prominent subsets (Vdelta1+ and Vdelta2+ cells) and differentiation states in 109 melanoma patients and 109 healthy controls. We additionally analysed the impact of gammadelta T-cells on overall survival (OS) calculated from the first dose of ipilimumab in melanoma patients. Higher median frequencies of Vdelta1+ cells and lower median frequencies of Vdelta2+ cells were identified in patients compared to healthy subjects (Vdelta1+: 30% versus 15%, Vdelta2+: 39% versus 64%, both p < 0.001). Patients with higher frequencies of Vdelta1+ cells (>=30%) had poorer OS (p = 0.043) and a Vdelta1+ differentiation signature dominated by late differentiated phenotypes. In contrast, higher frequencies of Vdelta2+ cells (>=39%) were associated with longer survival (p = 0.031) independent of the M category or lactate dehydrogenase level. Patients with decreasing frequencies of Vdelta2+ cells under ipilimumab treatment had worse OS and a lower rate of clinical benefit than patients without such decreases. Therefore, we suggest frequencies of both Vdelta1+ and Vdelta2+ cells as candidate biomarkers for outcome in melanoma patients following ipilimumab. Further studies are needed to validate these results and to clarify whether they represent prognostic associations or whether gammadelta T-cells are specifically and/or functionally linked to the mode of action of ipilimumab. PMID- 27400326 TI - Mechanistic Study of the Asymmetric Carbonyl-Ene Reaction between Alkyl Enol Ethers and Isatin Catalyzed by the N,N'-Dioxide-Mg(OTf)2 Complex. AB - The mechanism and origin of the stereoselectivity of the asymmetric carbonyl-ene reaction between N-methyl-protected isatin and 2-methyloxypropene catalyzed by the N,N'-dioxide-Mg(OTf)2 complex were investigated by DFT and ONIOM methods. The background reaction occurred via a two-stage, one-step mechanism with a high activation barrier of 30.4 kcal mol(-1) at the B3LYP-D3(BJ)/6-311G**(SMD, CH2Cl2)//B3LYP/6-31G*(SMD, CH2Cl2) level at 303 K. Good linear correlations between the global nucleophilicity index (N) and the activation energy barrier (DeltaG(?)) were found. The chiral N,N'-Mg(II) complex catalyst could enhance the electrophilicity of the isatin substrate by forming hexacoordinate Mg(II) reactive species. The substituent at the ortho positions of aniline combined with the aliphatic ring of the backbone in the chiral N,N'-dioxide ligand played an important role in the construction of a favorable "pocket-like" chiral environment (chiral pocket) around the Mg(II) center, directing the preferential orientation of the incoming substrate. An unfavorable steric arrangement in the re-face attack pathway translated into a more destabilizing activation strain of the ene substrate, enhancing enantiodifferentiation of two competing pathways for the desired R product. This work also suggested a new phosphine ligand (N-L1) for the formation of the Mg(II) complex catalyst for the asymmetric carbonyl-ene reaction. The chiral environment and Lewis acidity of the Mg(II) complex could be fine-tuned by introduction of P-donor units into the ligand for highly efficient asymmetric catalysis. PMID- 27400327 TI - Autoverification of routine coagulation assays in a multi-center laboratory. PMID- 27400325 TI - Rodents as a Source of Salmonella Contamination in Wet Markets in Thailand. AB - BACKGROUND: Few studies have been conducted on the presence of Salmonella in the rodents that inhabit the wet markets that play an important role in daily life in Southeast Asia. The results of studies of rodents as carriers of Salmonella vary greatly, ranging from an absence of Salmonella to high prevalences. Previous studies investigated habitats such as farms and urban and wild areas where there is less rodent-human interaction than in wet markets. Consequently, the potential role of rodents as reservoirs and transmitters of Salmonella in wet markets is of great interest. METHODS: Rodents were trapped in eight traditional wet markets in Thailand and identified to species level. Subsequently, they were screened for Salmonella and isolates were serotyped. RESULTS: A total of 110 rats (Rattus norvegicus and Rattus exulans) were examined. Overall, the prevalence of Salmonella in rats was 49.10%, but varied between 0% and 73.3% among markets. Three serovars were identified: Salmonella Typhimurium (30%), S. Weltevreden (12.7%), and S. 4,[5],12:i:- (6.4%). CONCLUSIONS: Our results show that rodents in wet markets are a potential reservoir of Salmonella due to the close contact they have with humans and food. The three isolated serovars, of which serovar S. 4,[5],12:i:- is reported for the first time in rodents, are among the 10 commonest serovars isolated from humans in Thailand. Thus, more attention should be paid to rodents as potential reservoirs of Salmonella. PMID- 27400328 TI - Circularly-Polarized Luminescence (CPL) from Chiral AIE Molecules and Macrostructures. AB - Circularly-polarized luminescence (CPL) has received new attention on the rise of applications to generate devices and biologically active probes. These applications require fluorophores that are not only chiral but also provide strong fluorescence intensity in aggregated state. Thus, a new research branch has opened up a few years ago, which allows CPL-active fluorophores to be emissive in aggregated-state. As a result, reports on the combination of the CPL property with the aggregation-induced emission (AIE) phenomenon have emerged. Herein the early design principles that have been reported until now to generate CPL-active AIE-active fluorophores (AIEgens) are summarized. In this regard the alignment of monomeric emitters in a chiral fashion, either in supramolecules, polymers or liquid crystals has been proven to be a successful approach. Additionally, first reports have appeared that demonstrate how to tackle the daunting task to furnish individual CPL-active AIEgens. PMID- 27400329 TI - Therapeutic approach to pain in neurodegenerative diseases: current evidence and perspectives. AB - INTRODUCTION: Neurodegenerative diseases are increasing in parallel to the lengthening of survival. The management of Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD-related disorders, and motor neuron diseases (MND), is mainly targeted to motor and cognitive impairment, with special care for vital functions such as breathing and feeding. Areas covered: The present review focuses on chronic pain in main neurodegenerative diseases, addressing current evidence on pain therapeutic management, pain frequency and clinical features, and possible pathophysiological mechanisms. The search on PubMed had no time limits and was performed by searching for the following key issues: pain, dementia, Alzheimer disease, Parkinson's disease, extrapyramidal disorders, motoneuronal disease, Amyotrophic lateral sclerosis, FXTAS, frequency, pathophysiology, treatments, therapy, efficacy, opioids, side effects. No controlled therapeutic trials and guidelines are currently available. The effects of current therapies such as L-Dopa or riluzole on pain symptoms are not clear. Emerging evidences on the possible anti-nociceptive effects of cannabis or botulinum toxin might be available soon. Expert commentary: Pain needs to be better evaluated and fully considered in the global management of neurodegenerative disease because a more focused treatment may have a positive impact on the global burden of these devastating disorders. PMID- 27400330 TI - Special Issue: "Perspectives on pain neuroscience education". PMID- 27400331 TI - Teaching patients about pain: It works, but what should we call it? PMID- 27400332 TI - Highly Hydrophobic Coatings from Waterborne Latexes. AB - This work reports on the formation of highly hydrophobic coatings from waterborne latexes able to form films at ambient temperature. The contact angle of film forming copolymers of 2-ethylhexyl acrylate and perfluorodecyl acrylate (PFDA) was limited to 114 degrees because flat surfaces were obtained. Attempts to increase the roughness of the film using blends of film-forming latexes with the latex of PFDA homopolymer (which is not film forming) were not successful under regular casting conditions because the PFDA particles accumulated at the film substrate interface. Film formation engineering allowed modifying the morphology of the film obtaining a contact angle of 137 degrees . PMID- 27400333 TI - Dinoflagellate-Related Amphidinolides from the Brazilian Octocoral Stragulum bicolor. AB - Benthic cnidarians are colonial marine animals that host a rich population of associated and symbiotic microorganisms. In a recent paper we described for the first time the isolation of amphidinolide P (1) from the Brazilian octocoral Stragulum bicolor. Amphidinolides and similar compounds had been previously reported only from dinoflagellates of the genus Amphidinium; thus the presence of 1 in the invertebrate opens intriguing questions on the role and occurrence of these molecules in marine ecosystems. Here we report the identification of four further amphidinolides from the same soft coral, including the known amphidinolide T1 (2) and the new analogues here named amphidinolides C4 (3), B8 (4), and B9 (5). The chemical structures have been elucidated mainly by extensive study of spectroscopic data. Cytotoxic activities of 3 and 4 were evaluated against the colon adenocarcinoma cell line HCT-116. PMID- 27400334 TI - Endocrine disrupters: we need research, biomonitoring and action. PMID- 27400335 TI - Pharmacologic implications of inflammatory comorbidity in bipolar disorder. AB - Bipolar disorder (BD) is a chronic illness associated with significant morbidity and mortality. Epidemiological studies have established a strong association between BD and inflammatory comorbidities. Furthermore, illness course is more severe and treatment resistant in BD with comorbid inflammatory disease and vice versa. Immune dysfunction has therefore been proposed as a key pathophysiological nexus sub-serving the bidirectional interaction between BD and inflammatory comorbidities. The foregoing observations have provided the rational and impetus for repurposing anti-inflammatory agents for the treatment of BD. Clinical trials have shown promising results for a variety of mechanistically diverse anti inflammatory agents. N-Acetylcysteine, infliximab, pioglitazone, celecoxib, aspirin, and omega-3 polyunsaturated fatty acids have shown an antidepressant effect in BD when administered adjunctively to conventional treatments. Currently, insufficient evidence exists to support the routine use of anti inflammatory agents in the treatment of BD with inflammatory comorbidities; however, several more clinical trials are current underway which may guide clinical application in the near future. Anti-inflammatory agents will likely be most useful for the subpopulation of BD where immune dysfunction is a driving pathogenic factor, such as in patients with inflammatory comorbidities. Future studies are striving to stratify subjects based on immune function or dysfunction in order to better understand which subset of BD subjects will benefit most from anti-inflammatory therapies. PMID- 27400336 TI - Oxidative stress: a potential link between emotional wellbeing and immune response. AB - Emotional wellbeing is central to normal health and good living. Persistent psychological stress often disrupts emotional wellbeing and triggers onset of neuropsychiatric ailments. An integrated, multisystemic stress response involving neuroinflammatory, neuroendocrine and metabolic cascades seem to have some causative links. Of particular interest are the neuroinflammatory processes. Psychological stress has been suggested to negatively affect normal functioning of the immune system contributing to the pathophysiology of some neuropsychiatric conditions. Thus examination of the interaction between the immune system and the central nervous system is likely to reveal molecular targets critical for development of potential therapeutic and preventive measures. This review is a summarized discussion of evidence linking impact of psychological stress on the immune system, with a particular emphasis on oxidative stress mechanisms by which mental stress potentially impacts immune function leading to activation of multiple cascades resulting in subsequent manifestation of psychiatric symptomologies. PMID- 27400337 TI - Magnetic Circular Dichroism Spectroscopy of meso-Tetraphenylporphyrin-Derived Hydroporphyrins and Pyrrole-Modified Porphyrins. AB - A large set of free-base and transition-metal 5,10,15,20-tetraphenyl-substituted chlorins, bacteriochlorins, and isobacteriochlorins and their pyrrole-modified analogues were investigated by combined UV-visible spectroscopy, magnetic circular dichroism (MCD), density functional theory (DFT), and time-dependent DFT (TDDFT) approaches and their spectral characteristics were compared to those of the parent compounds, free-base tetraphenylporphyrin 1H2 and chlorin 2H2. It was shown that the nature of the pyrroline substituents in the chlorin derivatives dictates their specific UV-vis and MCD spectroscopic signatures. In all hydroporphyrin-like cases, MCD spectroscopy suggests that the DeltaHOMO is smaller than the DeltaLUMO for the macrocycle-centered frontier molecular orbitals. DFT and TDDFT calculations were able to explain the large broadening of the UV-vis and MCD spectra of the chlorin diones and their derivatives compared to the other hydroporphyrins and hydroporphyrin analogues. This study contributes to the further understanding of the electronic effects of replacing a pyrrole in porphyrins by pyrrolines or other five-membered heterocycles (oxazoles and imidazoles). PMID- 27400338 TI - Care Coordination Strategies in Reforming Health Care: A Concept Analysis. AB - PROBLEM: With the growing number of individuals with chronic conditions and the associated healthcare costs, there is a need to improve how health care is delivered from an individual provider standpoint as well as a systemwide perspective. Such delivery can be accomplished through improved care coordination. CONCLUSION: Care coordination is a complex term that encompasses the full array of healthcare delivery activities across all systems of care. This includes organizing the care, improving quality of health care delivered, and achieving cost savings. In working to achieve this goal, the nurse is well suited to provide oversight in this process in assuring that the components of care coordination are conducted efficiently and effectively. PRACTICE IMPLICATIONS: While the nurse is the optimal provider for this position, the nurse's defined role in this process is not always clear. This article focuses on the term care coordination, which includes the definitions of care coordination, impact on nursing, attributes, antecedents, consequences, and empirical referents for this term. Care coordination is also differentiated from case management to add clarity to the role. PMID- 27400339 TI - Long-Term Tracking of the Osteogenic Differentiation of Mouse BMSCs by Aggregation-Induced Emission Nanoparticles. AB - Bone marrow-derived mesenchymal stem cells (BMSCs) have shown great potential for bone repair due to their strong proliferation ability and osteogenic capacity. To evaluate and improve the stem cell-based therapy, long-term tracking of stem cell differentiation into bone-forming osteoblasts is required. However, conventional fluorescent trackers such as fluorescent proteins, quantum dots, and fluorophores with aggregation-caused quenching (ACQ) characteristics have intrinsic limitations of possible interference with stem cell differentiation, heavy metal cytotoxicity, and self-quenching at a high labeling intensity. Herein, we developed aggregation-induced emission nanoparticles decorated with the Tat peptide (AIE-Tat NPs) for long-term tracking of the osteogenic differentiation of mouse BMSCs without interference of cell viability and differentiation ability. Compared with the ability of the commercial Qtracker 655 for tracking of only 6 passages of mouse BMSCs, AIE-Tat NPs have shown a much superior performance in long-term tracking for over 12 passages. Moreover, long-term tracking of the osteogenic differentiation process of mouse BMSCs was successfully conducted on the biocompatible hydroxyapatite scaffold, which is widely used in bone tissue engineering. Thus, AIE-Tat NPs have promising applications in tracking stem cell fate for bone repair. PMID- 27400340 TI - IL-12p40 gene-deficient BALB/c mice exhibit lower weight loss, reduced lung pathology and decreased sensitization to allergen in response to infection with pneumonia virus of mice. AB - Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and pneumonia in infants and pneumonia virus of mice (PVM) causes similar disease. BALB/c mice are highly susceptible, while C57BL/6 mice are more resistant to PVM. IL-12 was significantly more up-regulated in response to PVM infection in BALB/c than in C57BL/6 mice. IL-12p40-deficient neonatal and adult BALB/c mice showed significantly less weight loss than wild-type mice after PVM challenge. The percentage of regulatory T cells, as well as IFN-beta and IL-18 expression, was higher in the lungs of both neonatal and adult IL-12p40-/- mice. Adult IL-12p40-/ mice also showed enhanced TGF-beta and IL-10 expression and reduced inflammatory responses. Furthermore, IL-12p40-/- mice showed decreased sensitization to inhaled cockroach antigen after PVM infection when compared to wild-type mice. In conclusion, these data suggest that a depressed regulatory capacity in BALB/c mice to PVM infection results in enhanced immunopathology and sensitization to allergen. PMID- 27400342 TI - AJPH Global News. PMID- 27400341 TI - The Battle Over Bathrooms: A Solution Without a Problem. PMID- 27400345 TI - A Public Health of Consequence: Review of the August 2016 Issue of AJPH. PMID- 27400346 TI - Could Raising the Minimum Wage Improve the Public's Health? PMID- 27400347 TI - The Elusive Promise of LGBT Equality. PMID- 27400348 TI - Delivering Fresh Water: Critical Infrastructure, Environmental Justice, and Flint, Michigan. PMID- 27400349 TI - Editors on the Campaign Trail: Why Bernie Sanders Is Wrong on Health Care (and Hillary Clinton Is Right). PMID- 27400350 TI - Brown Responds: Why Hillary Clinton Is Wrong and Bernie Sanders Is Right. PMID- 27400351 TI - The Ongoing Opioid Prescription Epidemic: Historical Context. PMID- 27400352 TI - Capitalizing on Natural Experiments to Improve Our Understanding of Population Health. PMID- 27400353 TI - Public Health Detailing-A Successful Strategy to Promote Judicious Opioid Analgesic Prescribing. AB - OBJECTIVES: To evaluate knowledge and prescribing changes following a 2-month public health detailing campaign (one-to-one educational visits) about judicious opioid analgesic prescribing conducted among health care providers in Staten Island, New York City, in 2013. METHODS: Three detailing campaign recommendations were (1) a 3-day supply of opioids is usually sufficient for acute pain, (2) avoid prescribing opioids for chronic noncancer pain, and (3) avoid high-dose opioid prescriptions. Evaluation consisted of a knowledge survey, and assessing prescribing rates and median day supply per prescription. Prescribing data from the 3-month period before the campaign were compared with 2 sequential 3-month periods after the campaign. RESULTS: Among 866 health care providers visited, knowledge increased for all 3 recommendations (P < .01). After the campaign, the overall prescribing rate decreased similarly in Staten Island and other New York City counties (boroughs), but the high-dose prescribing rate decreased more in Staten Island than in other boroughs (P < .01). Median day supply remained stable in Staten Island and increased in other boroughs. CONCLUSIONS: The public health detailing campaign improved knowledge and likely prescribing practices and could be considered by other jurisdictions to promote judicious opioid prescribing. PMID- 27400354 TI - Evolution of Well-Being and Happiness After Increases in Consumption of Fruit and Vegetables. AB - OBJECTIVES: To explore whether improvements in psychological well-being occur after increases in fruit and vegetable consumption. METHODS: We examined longitudinal food diaries of 12 385 randomly sampled Australian adults over 2007, 2009, and 2013 in the Household, Income, and Labour Dynamics in Australia Survey. We adjusted effects on incident changes in happiness and life satisfaction for people's changing incomes and personal circumstances. RESULTS: Increased fruit and vegetable consumption was predictive of increased happiness, life satisfaction, and well-being. They were up to 0.24 life-satisfaction points (for an increase of 8 portions a day), which is equal in size to the psychological gain of moving from unemployment to employment. Improvements occurred within 24 months. CONCLUSIONS: People's motivation to eat healthy food is weakened by the fact that physical health benefits accrue decades later, but well-being improvements from increased consumption of fruit and vegetables are closer to immediate. POLICY IMPLICATIONS: Citizens could be shown evidence that "happiness" gains from healthy eating can occur quickly and many years before enhanced physical health. PMID- 27400358 TI - Kim et al. Respond. PMID- 27400359 TI - The Terminology of Community Health Workers. PMID- 27400360 TI - Austin Responds. PMID- 27400361 TI - Employment Status and Poor Adult Health Outcomes Among Lesbian, Gay, and Bisexual Individuals. PMID- 27400362 TI - Teixeira and Rodrigues Respond. PMID- 27400363 TI - The Protection to Women's Fundamental Rights Violated by the Zika Virus Epidemic. PMID- 27400365 TI - Nurse characteristics, leadership, safety climate, emotional labour and intention to stay for nurses: a structural equation modelling approach. AB - AIM: The aim of this study was to propose a theoretical model and apply it to examine the structural relationships among nurse characteristics, leadership characteristics, safety climate, emotional labour and intention to stay for hospital nurses. BACKGROUND: Global nursing shortages negatively affect the quality of care. The shortages can be reduced by retaining nurses. Few studies have independently examined the relationships among leadership, safety climate, emotional labour and nurses' intention to stay; more comprehensive theoretical foundations for examining nurses' intention to stay and its related factors are lacking. DESIGN: Cross-sectional. METHODS: A purposive sample of 414 full-time nurses was recruited from two regional hospitals in Taiwan. A structured questionnaire was used to collect data from November 2013-June 2014. Structural equation modelling was employed to test the theoretical models of the relationships among the constructs. RESULTS: Our data supported the theoretical model. Intention to stay was positively correlated with age and the safety climate, whereas working hours per week and emotional labour were negatively correlated. The nursing position and transformational leadership indirectly affected intention to stay; this effect was mediated separately by emotional labour and the safety climate. CONCLUSION: Our data supported the model fit. Our findings provide practical implications for healthcare organizations and administrators to increase nurses' intent to stay. Strategies including a safer climate, appropriate working hours and lower emotional labour can directly increase nurses' intent to stay. Transformational leadership did not directly influence nurses' intention to stay; however, it reduced emotional labour, thereby increasing intention to stay. PMID- 27400364 TI - Autofluorescence multiphoton microscopy for visualization of tissue morphology and cellular dynamics in murine and human airways. AB - The basic understanding of inflammatory airway diseases greatly benefits from imaging the cellular dynamics of immune cells. Current imaging approaches focus on labeling specific cells to follow their dynamics but fail to visualize the surrounding tissue. To overcome this problem, we evaluated autofluorescence multiphoton microscopy for following the motion and interaction of cells in the airways in the context of tissue morphology. Freshly isolated murine tracheae from healthy mice and mice with experimental allergic airway inflammation were examined by autofluorescence multiphoton microscopy. In addition, fluorescently labeled ovalbumin and fluorophore-labeled antibodies were applied to visualize antigen uptake and to identify specific cell populations, respectively. The trachea in living mice was imaged to verify that the ex vivo preparation reflects the in vivo situation. Autofluorescence multiphoton microscopy was also tested to examine human tissue from patients in short-term tissue culture. Using autofluorescence, the epithelium, underlying cells, and fibers of the connective tissue, as well as blood vessels, were identified in isolated tracheae. Similar structures were visualized in living mice and in the human airway tissue. In explanted murine airways, mobile cells were localized within the tissue and we could follow their migration, interactions between individual cells, and their phagocytic activity. During allergic airway inflammation, increased number of eosinophil and neutrophil granulocytes were detected that moved within the connective tissue and immediately below the epithelium without damaging the epithelial cells or connective tissues. Contacts between granulocytes were transient lasting 3 min on average. Unexpectedly, prolonged interactions between granulocytes and antigen-uptaking cells were observed lasting for an average of 13 min. Our results indicate that autofluorescence-based imaging can detect previously unknown immune cell interactions in the airways. The method also holds the potential to be used during diagnostic procedures in humans if integrated into a bronchoscope. PMID- 27400366 TI - Evaluation of the Ser-His Dipeptide, a Putative Catalyst of Amide and Ester Hydrolysis. AB - Efficient hydrolysis of amide bonds has long been a reaction of interest for organic chemists. The rate constants of proteases are unmatched by those of any synthetic catalyst. It has been proposed that a dipeptide containing serine and histidine is an effective catalyst of amide hydrolysis, based on an apparent ability to degrade a protein. The capacity of the Ser-His dipeptide to catalyze the hydrolysis of several discrete ester and amide substrates is investigated using previously described conditions. This dipeptide does not catalyze the hydrolysis of amide or unactivated ester groups in any of the substrates under the conditions evaluated. PMID- 27400368 TI - Detection of small subendocardial infarction using speckle tracking echocardiography in a rat model. AB - BACKGROUND: It is challenging to detect small nontransmural infarcts visually or automatically. As it is important to detect myocardial infarction (MI) at early stages, we tested the hypothesis that small nontransmural MI can be detected using speckle tracking echocardiography (STE) at the acute stage. METHODS: Minimal nontransmural infarcts were induced in 18 rats by causing recurrent ischemia-reperfusion of the left anterior descending (LAD) coronary artery, followed by a 30-min ligation and by reperfusion. A week later, the scar size was measured by histological analysis. Each rat underwent three echocardiography measurements: at baseline, 1 day post-MI, and 1 week post-MI. To measure the peak circumferential strain (CS), peak systolic CS, radial strain (RS), and time-to peak (TTP) of the CS, short-axis view of the apex was analyzed by a STE program. The TTP was normalized by the duration of the heart cycle to create percent change of heart cycle. RESULTS: Histological analysis after 1 week showed scar size of 4+/-6% at the anterior wall. At 24 h post-MI, the peak CS, peak systolic CS, and RS were reduced compared to baseline at the anterior wall due to the MI, and at the adjacent segments-the anterior septum and lateral wall, due to stunning (P<.05). However, only the anterior wall, the genuine damaged segment, showed prolonged TTP vs baseline (baseline 36%, 24 h 48%, P<.05). CONCLUSION: The TTP of the CS can distinguish between regions adjacent to MI (stunned or tethered) and MI, even in small nontransmural infarcts. PMID- 27400367 TI - Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings. AB - IMPORTANCE: The late effects of traumatic brain injury (TBI) are of great interest, but studies characterizing these effects are limited. OBJECTIVE: To determine whether TBI with loss of consciousness (LOC) is associated with an increased risk for clinical and neuropathologic findings of Alzheimer disease (AD), Parkinson disease (PD), and other dementias. DESIGN, SETTING, AND PARTICIPANTS: This study analyzed data from the Religious Orders Study (ROS), Memory and Aging Project (MAP), and Adult Changes in Thought study (ACT). All ROS and MAP participants and a subset of ACT participants consent to autopsy. Studies performed annual (ROS and MAP) or biennial (ACT) cognitive and clinical testing to identify incident cases of dementia and AD. The 7130 participants included members of a Seattle-area health care delivery system (ACT), priests and nuns living in orders across the United States (ROS), and Chicago-area adults in retirement communities (MAP). Of these, 1589 underwent autopsy. Primary hypothesis was that TBI with LOC would be associated with increased risk for AD and neurofibrillary tangles. Data were accrued from 1994 to April 1, 2014. EXPOSURES: Self-reported TBI when the participant was free of dementia, categorized as no more than 1 vs more than 1 hour of LOC. MAIN OUTCOMES AND MEASURES: Clinical outcomes included incident all-cause dementia, AD, and PD in all studies and incident mild cognitive impairment and progression of parkinsonian signs in ROS and MAP. Neuropathologic outcomes included neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis in all studies. RESULTS: Of 7130 participants (2879 [40.4%] men; overall mean [SD] age, 79.9 [6.9] years), 865 reported a history of TBI with LOC. In 45 190 person-years of follow-up, 1537 incident cases of dementia and 117 of PD were identified. No association was found between TBI with LOC and incident dementia (ACT: HR for TBI with LOC <=1 hour, 1.03; 95% CI, 0.83-1.27; HR for TBI with LOC >1 hour, 1.18; 95% CI, 0.77-1.78; ROS and MAP: HR for TBI with LOC <=1 hour, 0.87; 95% CI, 0.58-1.29; HR for TBI with LOC >1 hour, 0.84; 95% CI, 0.44-1.57) or AD (findings similar to those for dementia). Associations were found for TBI with LOC and incident PD in ACT (HR for TBI with LOC >1 hour, 3.56; 95% CI, 1.52-8.28) and progression of parkinsonian signs in ROS and MAP (odds ratio [OR] for TBI with LOC <=1 hour, 1.65; 95% CI, 1.23-2.21; OR for TBI with LOC >1 hour, 2.23; 95% CI, 1.16-4.29). Traumatic brain injury with LOC was associated with Lewy bodies (any Lewy body in ACT: RR for TBI with LOC >1 hour, 2.64; 95% CI, 1.40-4.99; Lewy bodies in substantia nigra and/or locus ceruleus in ACT: RR for TBI with LOC >1 hour, 3.30; 95% CI, 1.71-6.38; Lewy bodies in frontal or temporal cortex in ACT: RR for TBI with LOC >1 hour, 5.73; 95% CI, 2.18-15.0; ROS and MAP: RR for TBI with LOC <=1 hour, 1.64; 95% CI, 1.00 2.70; pooled RR for TBI with LOC <=1 hour, 1.59; 95% CI, 1.06-2.39) and microinfarcts (any cortical microinfarct in ROS and MAP: RR for TBI with LOC >1 hour, 2.12; 95% CI, 1.12-4.01; pooled RR for TBI with LOC >1 hour, 1.58; 95% CI, 1.06-2.35). CONCLUSIONS AND RELEVANCE: Pooled clinical and neuropathologic data from 3 prospective cohort studies indicate that TBI with LOC is associated with risk for Lewy body accumulation, progression of parkinsonism, and PD, but not dementia, AD, neuritic plaques, or neurofibrillary tangles. PMID- 27400369 TI - Hierarchical LiMn2O4 Hollow Cubes with Exposed {111} Planes as High-Power Cathodes for Lithium-Ion Batteries. AB - Hierarchical LiMn2O4 hollow cubes with exposed {111} planes have been synthesized using cube-shaped MnCO3 precursors, which are fabricated through a facile co precipitation reaction. Without surface modification, the as-prepared LiMn2O4 exhibits excellent cyclability and superior rate capability. Surprisingly, even over 70% of primal discharge capacity can be maintained for up to 1000 cycles at 50 C, and with only about 72 s of discharge time the as-prepared materials can deliver initial discharge capacity of 96.5 mA h g(-1). What is more, the materials have 98.4% and 90.7% capacity retentions for up to 100 cycles at 5 C under the temperatures of 25 and 60 degrees C, respectively. The superior electrochemical performance can be attributed to the unique hierarchical and interior hollow structure, exposed {111} planes, and high-quality crystallinity. PMID- 27400370 TI - The Shaping of Modern Pharmacy. PMID- 27400371 TI - Healthcare providers' perspectives on the acceptability and uptake of HPV vaccines in Zimbabwe. AB - BACKGROUND: Human papillomavirus (HPV) vaccines are a critical strategy in the prevention of cervical cancer, especially in countries like Zimbabwe where cervical cancer screening rates are low. In Zimbabwe, cervical cancer is the leading cause of cancer-related deaths in women but the HPV vaccine is not yet widely available. This study examined healthcare providers': (1) perceptions of current hospital practices and issues in cervical cancer prevention and treatment in Zimbabwe; (2) knowledge of HPV and HPV vaccines; and (3) perspectives on introducing HPV vaccination programs in Zimbabwe, including potential facilitators and barriers to successful implementation. METHOD: In-depth semi structured interviews were conducted at a rural hospital with 15 healthcare providers in Zimbabwe. Interviews included eight main questions and a number of additional probes that reflected the study's purpose. Data were analyzed using thematic analysis. RESULTS: Participants reported that women are not consistently being screened for cervical cancer. There were generally low levels of knowledge about HPV and HPV vaccines, but participants asked many questions indicating a desire to learn more. Although they were highly supportive of implementing HPV vaccination programs in Zimbabwe, they also identified a number of likely psychosocial, cultural, and logistical barriers to successful implementation, including cost, vaccine schedule, and hospital infrastructure. However, participants also provided a number of culturally relevant solutions, including education and community engagement. CONCLUSION: This study provides insight from healthcare providers about barriers to implementation and possible solutions that can be used by policy makers, practitioners, and other stakeholders to facilitate the successful implementation of forthcoming HPV immunization programs in Zimbabwe. PMID- 27400372 TI - Force-Time-Curve Comparison Between Weight-Lifting Derivatives. AB - The force-production characteristics of 3 weight-lifting derivatives were examined by comparing the force-time curves of each exercise. Sixteen resistance trained men performed repetitions of the hang power clean (HPC), jump shrug (JS), and hang high pull (HHP) on a force platform at several relative loads. Relative peak force (PFRel), relative impulse (IMPRel), peak rate of force development (PRFD), and time-normalized force-time curves of each exercise were compared. The JS produced greater PFRel than the HPC (P < .001, d = 1.38) and HHP (P < .001, d = 1.14), while there was no difference between the HPC and HHP (P = .338, d = 0.26). Similarly, the JS produced greater IMPRel than the HPC (P < .001, d = 0.52) and HHP (P = .019, d = 0.36). The HHP also produced greater IMPRel than the HPC (P = .040, d = 0.18). Finally, the JS produced greater PRFD than the HPC (P < .001, d = 0.73) and HHP (P = .001, d = 0.47), while there was no difference between the HPC and HHP (P = .192, d = 0.22). The HPC, JS, and HHP force-time profiles were similar during the first 75-80% of the movement; however, the JS produced markedly different force-time characteristics in the final 20-25% of the movement. The JS produced superior force-production characteristics, namely PFRel, IMPRel, and PRFD, as well as a unique force-time profile, compared with the HPC and HHP across several loads. PMID- 27400373 TI - The Jury Is Still Out on Working Memory Training. PMID- 27400374 TI - The effect of celecoxib on DNA methylation of CDH13, TFPI2, and FSTL1 in squamous cell carcinoma of the esophagus in vivo. AB - This study examined the in-vivo effect of the NSAID celecoxib on DNA methylation in the promoter region of the tumor-suppressor genes cadherin 13, tissue factor pathway inhibitor 12, and follistatin-like protein 1, and on apoptosis, in esophageal squamous cell carcinoma (ESCC). Forty-five patients who underwent an esophagectomy for ESCC were allocated to either a treatment group (n=22) or a control group (n=23). Patients in the treatment group were administered 800 mg/day of celecoxib for 14 days before surgery. Patients in the control group did not take any type of NSAID. Biopsies of the tumor were collected before surgery and tissue from the resection specimens after surgery. Methylation-specific PCR was used to measure DNA methylation and apoptosis was measured by flow cytometry. There was no difference in the proportion of patients with methylation for each of the genes between the patient groups before treatment. In those patients with pretreatment methylation, there was a significant reduction in the proportion with methylation and a significant increase in the corresponding messenger RNA expression after treatment with celecoxib. In those tissues in which there was a reduction in methylation following celecoxib treatment, there was a significant increase in the percentage of apoptotic cells, but not in the tissues with no change in methylation. In ESCC, in-vivo treatment with celecoxib is associated with a reduction in DNA methylation and increase in messenger RNA expression of tumor-suppressor genes, and increases in apoptosis. PMID- 27400375 TI - Genitourinary tumours in the targeted therapies era: new advances in clinical practice and future perspectives. AB - Genitourinary cancers represent a heterogeneous group of malignancies arising from genitourinary tract, and are responsible for almost 359 000 newly diagnosed cases and 58 420 related deaths in USA. Continuous advances in cancer genetics and genomics have contributed towards changing the management paradigms of these neoplasms. Neoangiogenesis, through the activation of the tyrosine-kinase receptors signalling pathways, represents the key mediator event in promoting tumour proliferation, differentiation, invasiveness and motility. In the last decade, several treatments have been developed with the specific aim of targeting different cell pathways that have been recognized to drive tumour progression. The following review attempts to provide a comprehensive overview of the literature, focusing on new advances in targeted therapies for genitourinary tumours. Furthermore, the promising results of the latest clinical trials and future perspectives will be discussed. PMID- 27400376 TI - Unsolved mysteries of Rag GTPase signaling in yeast. AB - The target of rapamycin complex 1 (TORC1) plays a central role in controlling eukaryotic cell growth by fine-tuning anabolic and catabolic processes to the nutritional status of organisms and individual cells. Amino acids represent essential and primordial signals that modulate TORC1 activity through the conserved Rag family GTPases. These assemble, as part of larger lysosomal/vacuolar membrane-associated complexes, into heterodimeric sub complexes, which typically comprise two paralogous Rag GTPases of opposite GTP /GDP-loading status. The TORC1-stimulating/inhibiting states of these heterodimers are controlled by various guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) complexes, which are remarkably conserved in various eukaryotic model systems. Among the latter, the budding yeast Saccharomyces cerevisiae has been instrumental for the elucidation of basic aspects of Rag GTPase regulation and function. Here, we discuss the current state of the respective research, focusing on the major unsolved issues regarding the architecture, regulation, and function of the Rag GTPase containing complexes in yeast. Decoding these mysteries will undoubtedly further shape our understanding of the conserved and divergent principles of nutrient signaling in eukaryotes. PMID- 27400377 TI - When federal science is muffling harm reduction by vaping. PMID- 27400378 TI - Byproduct Metal Availability Constrained by Dynamics of Carrier Metal Cycle: The Gallium-Aluminum Example. AB - Future availability of byproduct metals is not limited by geological stocks, but by the rate of primary production of their carrier metals, which in turn depends on the development of their in-use stocks, the product lifetimes, and the recycling rates. This linkage, while recognized conceptually in past studies, has not been adequately taken into account in resource availability estimates. Here, we determine the global supply potential for gallium up to 2050 based on scenarios for the global aluminum cycle, and compare it with scenarios for gallium demand derived from a dynamic model of the gallium cycle. We found that the gallium supply potential is heavily influenced by the development of the in use stocks and recycling rates of aluminum. With current applications, a shortage of gallium is unlikely by 2050. However, the gallium industry may need to introduce ambitious recycling- and material efficiency strategies to meet its demand. If in-use stocks of aluminum saturate or decline, a shift to other gallium sources such as zinc or coal fly ash may be required. PMID- 27400379 TI - Predictive factors for mortality in elderly Japanese patients with severe microscopic polyangiitis: A retrospective single-center study. AB - PURPOSE: To determine mortality and its predictive factors in elderly Japanese patients with severe microscopic polyangiitis (MPA). METHOD: This retrospective single-center study determined the mortality of 52 patients with MPA who were admitted to our geriatric medical center from 2002 to 2014. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality. RESULT: Mean age at onset of MPA was 73.2 years, and the one-year survival rate was 65.9%. Relapse was observed in 32.7%. Among variables at diagnosis, age, cardiomyopathy, central nervous system (CNS) involvement, alveolar hemorrhage, disease severity, the 1996 Five-Factor Score (FFS), and the 2009 FFS were associated with mortality in univariate analysis. Cardiomyopathy, CNS involvement, age >65 years, disease severity, Birmingham Vasculitis Activity Score, the 1996 FFS, and the 2009 FFS were associated with relapse-free survival in univariate analysis. CONCLUSION: We investigated mortality and relapse-free survival and their predictive factors in elderly Japanese patients with severe MPA. Age, disease severity, the 1996 FFS, and the 2009 FFS at diagnosis were prognostic factors for both mortality and relapse-free survival. PMID- 27400381 TI - Postpartum depression and infant-mother attachment security at one year: The impact of co-morbid maternal personality disorders. AB - Previous studies on effects of postpartum depression (PPD) on infant-mother attachment have been divergent. This may be due to not taking into account the effects of stable difficulties not specific for depression, such as maternal personality disorder (PD). Mothers (N=80) were recruited for a longitudinal study either during pregnancy (comparison group) or eight weeks postpartum (clinical group). Infants of mothers with depressive symptoms only or in combination with a PD diagnosis were compared with infants of mothers with no psychopathology. Depression and PD were assessed using self-report and clinical interviews. Infant mother attachment was assessed when infants were 13 months using Strange Situation Procedure (SSP). Attachment (in)security was calculated as a continuous score based on the four interactive behavioral scales of the SSP, and the conventional scale for attachment disorganization was used. PPD was associated with attachment insecurity only if the mother also had a PD diagnosis. Infants of PPD mothers without co-morbid PD did not differ from infants of mothers with no psychopathology. These results suggest that co-existing PD may be crucial in understanding how PPD impacts on parenting and infant social-emotional development. Stable underlying factors may magnify or buffer effects of PPD on parenting and child outcomes. PMID- 27400380 TI - Metagenome and Metatranscriptome Analyses Using Protein Family Profiles. AB - Analyses of metagenome data (MG) and metatranscriptome data (MT) are often challenged by a paucity of complete reference genome sequences and the uneven/low sequencing depth of the constituent organisms in the microbial community, which respectively limit the power of reference-based alignment and de novo sequence assembly. These limitations make accurate protein family classification and abundance estimation challenging, which in turn hamper downstream analyses such as abundance profiling of metabolic pathways, identification of differentially encoded/expressed genes, and de novo reconstruction of complete gene and protein sequences from the protein family of interest. The profile hidden Markov model (HMM) framework enables the construction of very useful probabilistic models for protein families that allow for accurate modeling of position specific matches, insertions, and deletions. We present a novel homology detection algorithm that integrates banded Viterbi algorithm for profile HMM parsing with an iterative simultaneous alignment and assembly computational framework. The algorithm searches a given profile HMM of a protein family against a database of fragmentary MG/MT sequencing data and simultaneously assembles complete or near complete gene and protein sequences of the protein family. The resulting program, HMM-GRASPx, demonstrates superior performance in aligning and assembling homologs when benchmarked on both simulated marine MG and real human saliva MG datasets. On real supragingival plaque and stool MG datasets that were generated from healthy individuals, HMM-GRASPx accurately estimates the abundances of the antimicrobial resistance (AMR) gene families and enables accurate characterization of the resistome profiles of these microbial communities. For real human oral microbiome MT datasets, using the HMM-GRASPx estimated transcript abundances significantly improves detection of differentially expressed (DE) genes. Finally, HMM-GRASPx was used to reconstruct comprehensive sets of complete or near-complete protein and nucleotide sequences for the query protein families. HMM-GRASPx is freely available online from http://sourceforge.net/projects/hmm graspx. PMID- 27400382 TI - Diagnostic accuracy of urine Helicobacter pylori antibody test in junior and senior high school students in Japan. AB - BACKGROUND: To prevent gastric cancer, a Helicobacter pylori test-and-treat strategy has been proposed. In Japan, routine urine examinations are performed to screen for kidney diseases; it is therefore convenient to screen for H. pylori infection via urine antibody (u-Ab) testing. AIM: To evaluate the diagnostic accuracy of u-Ab testing in students using 13 C-urea breath testing (UBT) as a standard. METHODS: The study population included 806 junior or senior high school students in Japan who provided urine samples and/or underwent UBT. Students with a positive u-Ab test or discrepant results between the u-Ab test and UBT were asked to provide additional stool and/or blood samples or to repeat the UBT. Urinary protein was detected using a urine test strip. RESULTS: The positive rates for the u-Ab test and UBT were 8.9% (71/795) and 5.5% (44/801), respectively. The u-Ab test showed 88.4% sensitivity and 95.7% specificity using UBT as a standard. In the final diagnoses, the u-Ab test showed 97.6% sensitivity, 96.5% specificity, 61.2% positive predictive value (PPV), and 99.9% negative predictive value (NPV). Of the 508 samples tested using a urine test strip, negative results were obtained for 450 subjects with a sensitivity of 90%, specificity of 97.9%, PPV of 66.7%, and NPV of 99.5%. Proteinuria was detected in 58 samples, with a sensitivity of 100%, specificity of 88.9%, PPV of 40%, and NPV of 100%. CONCLUSIONS: The u-Ab test is highly accurate and suitable for detecting H. pylori infection. However, the occurrence of proteinuria may yield false positive results. PMID- 27400383 TI - Enzymatic Cross-Linking of Resilin-Based Proteins for Vascular Tissue Engineering Applications. AB - Protein-based biomaterials have received significant attention for tissue engineering applications. For example, resilin-based protein gels have been produced with different cross-linking chemistries for applications in cartilage, cardiovascular, and vocal fold engineering. In this study, we investigate an alternative cross-linking chemistry to form resilin-based protein hydrogels and demonstrate the versatility of the gels for investigating cell response to matrix stiffness. Specifically, transglutaminase was used to cross-link proteins and resulted in gel surfaces more suitable for long-term cell attachment compared to those formed by a Mannich-type condensation reaction. Since matrix stiffness is an important determinant in modulating cell response, we first tuned matrix stiffness by varying total protein concentration. Next, we observed that matrix stiffness modulated cell spreading and endothelial differentiation of human mesenchymal stem cells. In particular, our results show that cells differentiated on our matrices, which have a stiffness similar to subendothelial layers, had statistically equivalent endothelial function compared to cells differentiated on hard glass surfaces. Thus, our protein-based matrix system is a promising tool to provide substrates favorable for long-term cell attachment and better mimics the native subendothelial environment compared to conventional hard culture substrates. PMID- 27400385 TI - Reversible phase modulation and hydrogen storage in multivalent VO2 epitaxial thin films. AB - Hydrogen, the smallest and the lightest atomic element, is reversibly incorporated into interstitial sites in vanadium dioxide (VO2), a correlated oxide with a 3d(1) electronic configuration, and induces electronic phase modulation. It is widely reported that low hydrogen concentrations stabilize the metallic phase, but the understanding of hydrogen in the high doping regime is limited. Here, we demonstrate that as many as two hydrogen atoms can be incorporated into each VO2 unit cell, and that hydrogen is reversibly absorbed into, and released from, VO2 without destroying its lattice framework. This hydrogenation process allows us to elucidate electronic phase modulation of vanadium oxyhydride, demonstrating two-step insulator (VO2)-metal (HxVO2) insulator (HVO2) phase modulation during inter-integer d-band filling. Our finding suggests the possibility of reversible and dynamic control of topotactic phase modulation in VO2 and opens up the potential application in proton-based Mottronics and novel hydrogen storage. PMID- 27400386 TI - Spectroscopic evidence for a type II Weyl semimetallic state in MoTe2. AB - In a type I Dirac or Weyl semimetal, the low-energy states are squeezed to a single point in momentum space when the chemical potential MU is tuned precisely to the Dirac/Weyl point. Recently, a type II Weyl semimetal was predicted to exist, where the Weyl states connect hole and electron bands, separated by an indirect gap. This leads to unusual energy states, where hole and electron pockets touch at the Weyl point. Here we present the discovery of a type II topological Weyl semimetal state in pure MoTe2, where two sets of Weyl points (, ) exist at the touching points of electron and hole pockets and are located at different binding energies above EF. Using angle-resolved photoemission spectroscopy, modelling, density functional theory and calculations of Berry curvature, we identify the Weyl points and demonstrate that they are connected by different sets of Fermi arcs for each of the two surface terminations. We also find new surface 'track states' that form closed loops and are unique to type II Weyl semimetals. This material provides an exciting, new platform to study the properties of Weyl fermions. PMID- 27400387 TI - Cooperative photoinduced metastable phase control in strained manganite films. AB - A major challenge in condensed-matter physics is active control of quantum phases. Dynamic control with pulsed electromagnetic fields can overcome energetic barriers, enabling access to transient or metastable states that are not thermally accessible. Here we demonstrate strain-engineered tuning of La2/3Ca1/3MnO3 into an emergent charge-ordered insulating phase with extreme photo-susceptibility, where even a single optical pulse can initiate a transition to a long-lived metastable hidden metallic phase. Comprehensive single-shot pulsed excitation measurements demonstrate that the transition is cooperative and ultrafast, requiring a critical absorbed photon density to activate local charge excitations that mediate magnetic-lattice coupling that, in turn, stabilize the metallic phase. These results reveal that strain engineering can tune emergent functionality towards proximal macroscopic states to enable dynamic ultrafast optical phase switching and control. PMID- 27400388 TI - Reconfiguring active particles by electrostatic imbalance. AB - Active materials represent a new class of condensed matter in which motile elements may collectively form dynamic, global structures out of equilibrium. Here, we present a general strategy to reconfigure active particles into various collective states by introducing imbalanced interactions. We demonstrate the concept with computer simulations of self-propelled colloidal spheres, and experimentally validate it in a two-dimensional (2D) system of metal-dielectric Janus colloids subjected to perpendicular a.c. electric fields. The mismatched, frequency-dependent dielectric responses of the two hemispheres of the colloids allow simultaneous control of particle motility and colloidal interactions. We realized swarms, chains, clusters and isotropic gases from the same precursor particle by changing the electric-field frequency. Large-scale polar waves, vortices and jammed domains are also observed, with the persistent time-dependent evolution of their collective structure evoking that of classical materials. This strategy of asymmetry-driven active self-organization should generalize rationally to other active 2D and three-dimensional (3D) materials. PMID- 27400389 TI - Coupling Reaction of Enol Derivatives with Silyl Ketene Acetals Catalyzed by Gallium Trihalides. AB - A cross-coupling reaction between enol derivatives and silyl ketene acetals catalyzed by GaBr3 took place to give the corresponding alpha-alkenyl esters. GaBr3 showed the most effective catalytic ability, whereas other metal salts such as BF3 ?OEt2 , AlCl3 , PdCl2 , and lanthanide triflates were not effective. Various types of enol ethers and vinyl carboxylates as enol derivatives are amenable to this coupling. The scope of the reaction with silyl ketene acetals was also broad. We successfully observed an alkylgallium intermediate by using NMR spectroscopy, suggesting a mechanism involving anti-carbogallation among GaBr3 , an enol derivative, and a silyl ketene acetal, followed by syn-beta alkoxy elimination from the alkylgallium. Based on kinetic studies, the turnover limiting step of the reaction using a vinyl ether and a vinyl carboxylate involved syn-beta-alkoxy elimination and anti-carbogallation, respectively. Therefore, the leaving group had a significant effect on the progress of the reaction. Theoretical calculations analysis suggest that the moderate Lewis acidity of gallium would contribute to a flexible conformational change of the alkylgallium intermediate and to the cleavage of the carbon-oxygen bond in the beta-alkoxy elimination process, which is the turnover-limiting step in the reaction between a vinyl ether and a silyl ketene acetal. PMID- 27400390 TI - The Past and Future of the Affordable Care Act. PMID- 27400391 TI - Off-label Use of Quetiapine in Medical Inpatients and Postdischarge. PMID- 27400392 TI - Two new 4,6-dimethyl-3,4-dihydrochromen-2-one derivatives from Craterellus odoratus. AB - Two rare types of 4,6-dimethyl-3,4-dihydrochromen-2-one derivatives, named cralactones A and B (1 and 2), were isolated from the culture broth of Craterellus odoratus. The structures of the new ones were established on the basis of extensive spectroscopic analysis, and it was found that the new compounds did not show pancreatic lipase inhibitory activity. Compounds 1 and 2 are the first examples of 4,6-dimethyl-3,4-dihydrochromen-2-one. PMID- 27400393 TI - Supercapacitive microbial fuel cell: Characterization and analysis for improved charge storage/delivery performance. AB - Supercapacitive microbial fuel cells with various anode and cathode dimensions were investigated in order to determine the effect on cell capacitance and delivered power quality. The cathode size was shown to be the limiting component of the system in contrast to anode size. By doubling the cathode area, the peak power output was improved by roughly 120% for a 10ms pulse discharge and internal resistance of the cell was decreased by ~47%. A model was constructed in order to predict the performance of a hypothetical cylindrical MFC design with larger relative cathode size. It was found that a small device based on conventional materials with a volume of approximately 21cm(3) would be capable of delivering a peak power output of approximately 25mW at 70mA, corresponding to ~1300Wm(-3). PMID- 27400394 TI - Molecular imaging with CARS micro-spectroscopy. AB - After more than a decade of instrument and method development, broadband coherent anti-Stokes Raman scattering (CARS) micro-spectroscopy is beginning to live up to its potential as a label-free imaging modality that can rapidly generate high resolution images with full vibrational spectra at each image pixel. Presently these instruments are able to obtain quantitative, spatially resolved information on lipids from the CH stretch region of the Raman spectrum, and some instrument designs facilitate acquisition of high quality fingerprint spectra, containing information on a host of molecular species including structural proteins, nucleotides, and metabolites. While most of the existing instruments are research projects themselves, it appears that the relevant technologies are maturing so that commercially available instruments may not be too far in the future, making this remarkable imaging modality widely available. PMID- 27400395 TI - A Novel Chemoenzymatic Synthesis of Sulfated Type 2 Tumor-Associated Carbohydrate Antigens by Transglycosylation of Sulfated Lewis X Oxazoline Catalyzed by Keratanase II. AB - Sulfated type 2 carbohydrate chains are known tumor-associated carbohydrate antigens (TACAs). Many reports on cancer vaccines employing TACAs as specific antigens have been published, but structurally specified sulfated TACAs have not been used because of the low natural abundance and difficulties in chemical synthesis. We demonstrate for the first time the synthesis of the sulfated type 2 TACAs with an l-fucose branch by keratanase-II-catalyzed transglycosylation of the sulfated Lewis X (Galbeta(1->4)[Fucalpha(1->3)]GlcNAc(6-OSO3- ); su-Lex ) oxazoline derivative. Two keratanase IIs (from Bacillus sp. Ks36 and Bacillus circulans KsT202) efficiently catalyzed the transglycosylation reaction of the su Lex oxazoline derivative, thereby giving the su-Lex dimer as the main product in good yields. Structural analysis of the oligomers confirmed exclusive formation of the beta(1->3) glycosidic bond. PMID- 27400396 TI - Submicron Patterning of Polymer Brushes: An Unexpected Discovery from Inkjet Printing of Polyelectrolyte Macroinitiators. AB - Using an electrostatic-based super inkjet printer we report the high-resolution deposition of polyelectrolyte macroinitiators and subsequent polymer brush growth using SI-ARGET-ATRP. We go on to demonstrate for the first time a submicron patterning phenomenon through the addition of either a like charged polyelectrolyte homopolymer or through careful control of ionic strength. As a result patterning of polymer brushes down to ca. 300 nm is reported. We present a possible mechanistic model and consider how this may be applied to other polyelectrolyte-based systems as a general method for submicron patterning. PMID- 27400397 TI - Rare Complications of Migraine With Aura. AB - PURPOSE: To provide a review of the diagnostic criteria, pathophysiology, and potential treatments of the complications of migraine as identified by the International Classification of Headache Disorders 3beta, with the exception of status migrainosus. METHOD: Migraine with aura may be associated with the onset of rare, but significantly disabling neurological symptoms. This review provides an overview of the associated complications that may arise from migraine with aura. CONCLUSION: The complications of migraine that arise from migraine aura are infrequently encountered in clinical practice; however, they can be severely disabling for patients. As these conditions are encountered, thorough diagnostic evaluation is necessary. In some cases, it may be difficult to find a consistently reliable therapeutic option for these patients; however, as more cases enter the literature, a greater understanding of these conditions and how to treat them may arise. PMID- 27400398 TI - A modified natural cycle results in higher live birth rate in vitrified-thawed embryo transfer for women with regular menstruation. AB - There is no consensus regimen for the optimal endometrial preparation for cryopreservation and vitrified-thawed embryo transfer cycles. This is largely caused by the lack of sufficient investigation and analyses on the respective pregnancy and perinatal outcomes by different regimens. This study aimed to compare both pregnancy and perinatal outcomes between the modified natural and artificial cycles in vitrified-thawed day three embryo transfer for women with regular menstruation. A total of 1,482 vitrified-thawed day three embryo transfer cycles were reviewed including 427 modified natural cycles (NC), 132 ovulation induction cycles (OC), 794 artificial cycles (AC), and 129 GnRH agonist artificial cycles (GAC). The primary outcome that was evaluated was live birth rate. The NC regimen demonstrated a higher rate of ongoing pregnancy (43.8% vs. 30.2%, P = 0.002) and a lower rate of late abortion (2.8% vs. 14.0%, P = 0.003) than the GAC regimen as well as a higher implantation rate (31.9% vs. 27.1%, P = 0.008) and live birth rate (43.1% vs. 34.1%, P = 0.002) than the AC regimen. A significantly higher peak endometrial thickness before transfer was observed in patients using the NC and GAC regimens (10.0 +/- 1.7, 9.9 +/- 2.4) compared to the AC regimens (9.2 +/- 1.5, P = 0.000). Multivariate logistic regression showed that the NC protocol was associated with a higher live birth rate. There were no significant differences in rates of pregnancy complications, neonatal mortality, birth defects, mean birth weight, and other perinatal outcomes among the regimens. Modified natural cycle endometrial preparation regimen for vitrified thawed day three embryo transfer is associated with superior live birth pregnancy outcomes compared to artificial cycles. Future studies are warranted to investigate the underlying biologic mechanisms of these findings. Abbreviations ART: assisted reproductive technology; BMI: body mass index; FET: frozen-thawed embryo transfer; HCG: human chorionic gonadotropin; IVF: in-vitro fertilization; IVF-ET: in-vitro fertilization and embryo transfer; OHSS: ovarian hyperstimulation syndrome; RCTs: randomized controlled trials. PMID- 27400399 TI - Laccase multigene families in Agaricomycetes. AB - Here we present the results of the exploration of laccase multigene families (MGFs) in basidiomycetous fungi from different taxonomic groups using a next generation sequencing (NGS) technology. In our study, multiple laccase genes were identified in all of the investigated fungi (13 species) from Polyporaceae, Phanerochaetaceae, Meruliaceae, Pleurotaceae, Physalacriaceae, and Peniophoraceae families. It was shown that phylogenetic positioning of the newly identified sequences exhibit patterns of clusterization with respect to enzyme properties. This can be a potentially useful tool for selecting naturally existing laccases with different physicochemical characteristics relevant to different biotechnological applications. Moreover, the method developed in this study can be used in the screening of environmental samples and fast characterization of laccase MGFs in newly identified fungal species. PMID- 27400400 TI - Bifunctional Thioureas with alpha-Trifluoromethyl or Methyl Groups: Comparison of Catalytic Performance in Michael Additions. AB - Thioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis of bifunctional thioureas with a chiral moiety that include either a trifluoromethyl or methyl group. Their catalytic performance in representative Michael addition reactions was used in an effort to compare the electronic effects of the fluorination at the methyl group. The observed differences concerning yields and ee values cannot be attributed solely to the different steric environments; theoretical results indicate distinct interactions within the corresponding transition states. The calculated transition states show that the fluorinated catalysts have stronger N-H...O and C-H...F hydrogen bonds, while the nonfluorinated systems have C-H...pi contacts. These results have shown that a variety of hydrogen-bonding interactions are important in determining the yield and selectivity of thiourea organocatalysis. These details can be further exploited in catalyst design. PMID- 27400401 TI - United States Health Care Reform: Progress to Date and Next Steps. AB - IMPORTANCE: The Affordable Care Act is the most important health care legislation enacted in the United States since the creation of Medicare and Medicaid in 1965. The law implemented comprehensive reforms designed to improve the accessibility, affordability, and quality of health care. OBJECTIVES: To review the factors influencing the decision to pursue health reform, summarize evidence on the effects of the law to date, recommend actions that could improve the health care system, and identify general lessons for public policy from the Affordable Care Act. EVIDENCE: Analysis of publicly available data, data obtained from government agencies, and published research findings. The period examined extends from 1963 to early 2016. FINDINGS: The Affordable Care Act has made significant progress toward solving long-standing challenges facing the US health care system related to access, affordability, and quality of care. Since the Affordable Care Act became law, the uninsured rate has declined by 43%, from 16.0% in 2010 to 9.1% in 2015, primarily because of the law's reforms. Research has documented accompanying improvements in access to care (for example, an estimated reduction in the share of nonelderly adults unable to afford care of 5.5 percentage points), financial security (for example, an estimated reduction in debts sent to collection of $600-$1000 per person gaining Medicaid coverage), and health (for example, an estimated reduction in the share of nonelderly adults reporting fair or poor health of 3.4 percentage points). The law has also begun the process of transforming health care payment systems, with an estimated 30% of traditional Medicare payments now flowing through alternative payment models like bundled payments or accountable care organizations. These and related reforms have contributed to a sustained period of slow growth in per-enrollee health care spending and improvements in health care quality. Despite this progress, major opportunities to improve the health care system remain. CONCLUSIONS AND RELEVANCE: Policy makers should build on progress made by the Affordable Care Act by continuing to implement the Health Insurance Marketplaces and delivery system reform, increasing federal financial assistance for Marketplace enrollees, introducing a public plan option in areas lacking individual market competition, and taking actions to reduce prescription drug costs. Although partisanship and special interest opposition remain, experience with the Affordable Care Act demonstrates that positive change is achievable on some of the nation's most complex challenges. PMID- 27400402 TI - Optimization and development of a high-performance liquid chromatography method for the simultaneous determination of vitamin E and carotenoids in tomato fruits. AB - A simple and reliable high-performance liquid chromatography method was developed and validated for the simultaneous determination of lipophilic antioxidants in tomato fruits using C30 column operated at 15 degrees C and a gradient mobile phase based on acetonitrile/methanol/dichloromethane in a total run time of 30 min. Diode array and fluorescence detectors were used respectively for the detection of carotenoids (lutein, zeaxanthin, cryptoxanthin, lycopene, and beta carotene) and vitamin E analogs (alpha-, beta-, gamma-, and delta-tocopherols, and tocotrienols). The best extraction yield of analytes in tomato fruits was achieved by employing ethyl acetate/hexane (1:1, v/v) after several treatments with various solvents. In addition, low extraction yields were obtained for carotenoids compared to tocopherols by adopting solid-phase extraction as a second clean-up step. The method was validated on the basis of recovery, precision, linearity, and limit of detection and quantification using spiked tomato samples. The method was applied to cherry and medium-sized tomato fruits. Lycopene was found to be present in largest amount in tomato pulp, followed by beta-carotene and lutein. Due to its simplicity, rapidity, and efficiency, the method is suitable for routine analysis of lipophilic antioxidants in tomato fruits, and may also be applied to other vegetables of similar phytochemical profiles. PMID- 27400403 TI - Inferring HIV-1 Transmission Dynamics in Germany From Recently Transmitted Viruses. AB - BACKGROUND: Although HIV continues to spread globally, novel intervention strategies such as treatment as prevention (TasP) may bring the epidemic to a halt. However, their effective implementation requires a profound understanding of the underlying transmission dynamics. METHODS: We analyzed parameters of the German HIV epidemic based on phylogenetic clustering of viral sequences from recently infected seroconverters with known infection dates. Viral baseline and follow-up pol sequences (n = 1943) from 1159 drug-naive individuals were selected from a nationwide long-term observational study initiated in 1997. Putative transmission clusters were computed based on a maximum likelihood phylogeny. Using individual follow-up sequences, we optimized our clustering threshold to maximize the likelihood of co-clustering individuals connected by direct transmission. RESULTS: The sizes of putative transmission clusters scaled inversely with their abundance and their distribution exhibited a heavy tail. Clusters based on the optimal clustering threshold were significantly more likely to contain members of the same or bordering German federal states. Interinfection times between co-clustered individuals were significantly shorter (26 weeks; interquartile range: 13-83) than in a null model. CONCLUSIONS: Viral intraindividual evolution may be used to select criteria that maximize co clustering of transmission pairs in the absence of strong adaptive selection pressure. Interinfection times of co-clustered individuals may then be an indicator of the typical time to onward transmission. Our analysis suggests that onward transmission may have occurred early after infection, when individuals are typically unaware of their serological status. The latter argues that TasP should be combined with HIV testing campaigns to reduce the possibility of transmission before TasP initiation. PMID- 27400404 TI - Challenges in Estimating Effectiveness of Condom Distribution Campaigns to Prevent HIV Transmission. PMID- 27400405 TI - Post-mortem proteolysis and tenderisation are more rapid and extensive in female duck breast muscle. AB - The post-mortem proteolysis and tenderisation between male and female duck breast muscles were compared. The results showed that MU-calpain activity, desmin content and shear force decreased more quickly in female than in male samples stored at 5 degrees C. It is suggested that the post-mortem proteolysis and tenderisation are more rapid and extensive in female duck breast muscle. PMID- 27400406 TI - Association study involving polymorphisms in IL-6, IL-1RA, and CTLA4 genes and rheumatic heart disease in New Zealand population of Maori and Pacific ancestry. AB - INTRODUCTION: Rheumatic fever (RF) incidence among New Zealand (NZ) individuals of Polynesian (Maori and Pacific) ancestry remains among the highest in the world. Polymorphisms in the IL-6, IL1RN, and CTLA4 genes have been associated with RF, and their products are modulated by new medications. Confirmation of these previous associations could help guide clinical approaches. We aimed to test IL-6, IL-1RA (IL1RN), and CTLA4 functional SNPs in 204 rheumatic heart disease (RHD) patients and 116 controls of Maori and Pacific ancestry. MATERIAL AND METHOD: Self-reported ancestry of the eight great-grandparents defined ancestry of participants. Severity of carditis was classified according to the 2012 World Heart Federation guideline for the echocardiographic diagnosis of RHD. The IL-6 promoter rs1800797, IL1RN rs447713 and CTLA4 rs3087243 SNPs were genotyped by Taqman. Correlations were assessed by logistic regression analysis adjusting for gender and ancestry. RESULTS: The IL-6 rs1800797 variant was significantly associated with RHD with carriers of the GG genotype 6.09 (CI 1.23; 30.23) times more likely to develop RHD than the carriers of the AA genotype (P=0.027). No significant associations with RHD were found for the IL1RN rs447713 and CTLA4 rs3087243 SNPs. Patients carrying the G allele (GG plus AG genotype) for the IL1RN rs447713 SNP had 2.36 times (CI 1.00; 5.56) more severe carditis than those without this allele (the AA genotype) (P=0.049). CONCLUSION: The IL-6 promoter rs1800797 (-597G/A) SNP may influence susceptibility to RHD of people of Maori and Pacific ancestry living in NZ. The IL1RN rs447713 SNP may influence the severity of carditis in this population. PMID- 27400407 TI - Crabs grab strongly depending on mechanical advantages of pinching and disarticulation of chela. AB - A small morphological variation of an organ may cause a major change of its function in animal evolution. The function of decapod chela varies considerably among taxa, between sex, and even within an individual, but also retains a simple mechanism of motion. Therefore, the decapod chela is a suitable structure to study the evolutionary process of functional diversifications, although the relationship of form and function is inadequately understood, yet. We estimated the mechanical advantages of pinching and passive disarticulation resistance, and chela size relative to the carapace in 317 chelae of 168 decapod specimens, and compared these indices with the functions of each chela. Our study revealed that mechanical advantages of pinching efficiency and passive disarticulation resistance were greatest in shell-crushing chelae, followed by gripping and pinching chelae, whereas the chela size relative to the carapace was not related to differences among these functions. We also found that the chelae are designed to retain the ratio between depth and width of the proximal dactylus. In the evolutionary process of decapods, the diversifications of chela functions were accompanied by the diversifications of the mechanical advantages, and played an essential role in their ecological diversification. J. Morphol. 277:1259-1272, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400409 TI - Nanostructured water and carbon dioxide inside collapsing carbon nanotubes at high pressure. AB - We present simulations of the collapse under hydrostatic pressure of carbon nanotubes containing either water or carbon dioxide. We show that the molecules inside the tube alter the dynamics of the collapse process, providing either mechanical support and increasing the collapse pressure, or reducing mechanical stability. At the same time the nanotube acts as a nanoanvil, and the confinement leads to the nanostructuring of the molecules inside the collapsed tube. In this way, depending on the pressure and on the concentration of water or carbon dioxide inside the nanotube, we observe the formation of 1D molecular chains, 2D nanoribbons, and even molecular single and multi-walled nanotubes. The structure of the encapsulated molecules correlates with the mechanical response of the nanotube, opening up opportunities for the development of new devices or composite materials. Our analysis is quite general and it can be extended to other molecules in carbon nanotube nanoanvils, providing a strategy to obtain a variety of nano-objects with controlled features. PMID- 27400410 TI - Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients. AB - IMPORTANCE: Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during the last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison with the natural course of the disease. OBJECTIVE: To compare the long-term outcome of patients who underwent allogeneic HSCT with control patients who did not among a cohort with juvenile MLD. DESIGN, SETTING, AND PARTICIPANTS: Patients with juvenile MLD born between 1975 and 2009 and who received HSCT at a median age of 7 years (age range, 1.5-18.2 years) and nontransplanted patients with juvenile MLD born between 1967 and 2007 were included in this case-control study. The median follow-up after HSCT was 7.5 years (range, 3.0-19.7 years). Patients underwent HSCT at 3 German centers between 1991 and 2012. The analysis was done between July 2014 and August 2015. MAIN OUTCOMES AND MEASURES: Survival and transplantation-related mortality, loss of gross motor function (Gross Motor Function Classification in MLD), loss of any language function, and magnetic resonance imaging (MRI) severity score for cerebral changes. To explore prognostic factors at baseline, patients who underwent HSCT (hereafter, transplanted patients) were a priori divided into stable vs progressive disease, according to gross motor and cognitive function. RESULTS: Participants were 24 transplanted patients (11 boys, 13 girls) and 41 control patients (22 boys, 19 girls) who did not receive transplantation (hereafter, nontransplanted patients) with juvenile MLD. Among the transplanted patients, 4 children died of transplantation-related mortality, and 2 additional children died of rapid MLD progression 1.5 and 8.6 years after HSCT, resulting in a 5-year survival of 79% (19 of 24). Among the nontransplanted patients, 5-year survival after disease onset was 100% (41 of 41). However, 11 died of MLD progression, resulting in similar overall survival within the observation period. Nine of the long-term survivors after HSCT had disease progression, while 11 showed stable disease. Compared with the nontransplanted patients, the transplanted patients were less likely to lose their gross motor or language function and demonstrated significantly lower MRI severity scores at the latest examination. Patients after HSCT were more likely to have a stable disease course when undergoing HSCT at an early stage with no or only mild gross motor deficits (Gross Motor Function Classification in MLD level 0 or 1) and an IQ of at least 85, when age at disease onset was older than 4 years, or when MRI severity scores were low (preferably <=17). CONCLUSIONS AND RELEVANCE: Among patients with juvenile MLD, patients who underwent HSCT had a better gross motor and language outcome and lower MRI severity scores compared with nontransplanted patients. Transplantation at a presymptomatic or early symptomatic stage of juvenile MLD is associated with a reasonable chance for disease stabilization. PMID- 27400411 TI - Digital ulcers in systemic sclerosis are associated with microangiopathic abnormalities of perilesional skin as assessed by capillaroscopy. PMID- 27400412 TI - Left ventricular pseudoaneurysm after mitral valve replacement. AB - Development of left ventricular pseudoaneurysm is a rare complication of mitral valve surgery and requires urgent surgical intervention. We describe a case of pseudoaneurysm of membranous septum following repeat mitral valve replacement with the use of multimodality imaging. PMID- 27400414 TI - The effect of potential fall distance on hormonal response in rock climbing. AB - The aim of this study was to examine the effect of alterations in potential lead fall distance on the hormonal responses of rock climbers. Nine advanced female climbers completed two routes while clipping all (PRO-all) or half (PRO-1/2) of the fixed points of protection. Venous blood samples were analysed for total catecholamines, noradrenaline (norepinephrine), adrenaline (epinephrine), dopamine, lactate, cortisol and serotonin. Differences between the two conditions pre, immediately post and 15 min post climbing were assessed using a 2 * 3 repeated measures ANOVA. All hormones and blood lactate concentrations increased significantly (P < 0.05) immediately post climb, except for cortisol. Peak cortisol concentrations did not occur until 15 min post ascent. Further, significant interactions between climbing and clipping conditions were found for total catecholamines (890% of basal concentration in PRO-1/2 vs. 568% in PRO all), noradrenaline (794% vs. 532%) and dopamine (500% vs. 210%). There were no significant interactions for adrenaline (1920% vs. 1045%), serotonin (150% vs. 127%) or lactate (329% vs. 279%). The study showed a greater catecholamine response with an increase in potential lead fall distance. The most pronounced increases seen in catecholamine concentration were reported for dopamine and noradrenaline. PMID- 27400413 TI - Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma. AB - Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM. In this study, we describe a mechanism by which increased expression of peptidyl arginine deiminase 2 (PADI2) by BMMSCs in patients with MGUS and MM directly alters malignant plasma cell phenotype. We identify PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through its enzymatic deimination of histone H3 arginine 26, PADI2 activity directly induces the upregulation of interleukin-6 expression. This leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26. PMID- 27400415 TI - The potential for cross-addiction in post-bariatric surgery patients: Considerations for primary care nurse practitioners. AB - BACKGROUND AND PURPOSE: Possible mental health issues for post-bariatric surgery patients include the development of cross-addictions after the rapid weight loss period. No validated screening tool to assess for possible cross-addictions exists. The main purpose of this study was to develop recommendations for modifying an existing addiction screening tool (the Shorter PROMIS Questionnaire) for use by primary care providers. METHODS: A qualitative descriptive design was used with triangulation of input from the scholarly literature, content experts (CEs), and post-bariatric surgery patients. Three focus groups were conducted with post-bariatric surgery patients (n = 12) with the same questions asked of the CEs (n = 3). Content analysis was used to analyze the transcripts. CONCLUSIONS: The following themes regarding addictions after bariatric surgery were identified through consensus: alcohol, gambling, shopping, exercise, food starving/bingeing, and sexuality/relationships. Dissonant themes included caffeine and tobacco by the post-bariatric surgery patients and prescription/illicit medications by the CEs. IMPLICATIONS FOR PRACTICE: Targeted screening for early identification of problem behaviors by primary care providers may result in appropriate referral to and management by mental health providers, assisting ongoing success of bariatric surgery. PMID- 27400416 TI - Use and satisfaction with the Healthcare System of the chronic pain patients in Spain: results from a nationwide study. AB - OBJECTIVE: To analyze the use of healthcare resources by chronic pain (CP) patients in Spain and their satisfaction with them. RESEARCH DESIGN AND METHODS: A nationwide, cross-sectional study was carried out on a representative sample of 1957 Spanish adults. A telephone survey was conducted with the aim of analyzing the prevalence of CP, the characteristics and consequences of pain, the use of healthcare resources and patients' satisfaction with them. Descriptive, bivariate and multivariate analyses were performed. RESULTS: Of the 1957 subjects interviewed, 325 suffered CP. The mean duration of CP was 10 years (SD: 11.3) and 48.9% of the CP sufferers reported severe/unbearable pain. Moreover, about 30% felt sad/very sad or anxious/very anxious, 24.4% had been on sick leave, 12% had left/lost their jobs and 47.2% considered their pain affected their families. Likewise, 92.9% had consulted a healthcare professional due to their CP, on average 3.49 times (SD: 3.9), and 69.2% took medication. In addition, 67.3% and 63.8% were satisfied/very satisfied with the care and the healthcare information they received, respectively. Individuals who reported headache (OR = 0.34) and feeling sad (OR =0.38) were least satisfied with the care they received. In addition, CP sufferers who made greater use of consultations were those who had left/lost their jobs (beta = 1.44), those who took medication (beta = 1.67), those who considered their pain affected their families (beta = 0.97) and those with a shorter duration of pain (beta = -0.003). CONCLUSIONS: CP produces relevant demands on healthcare resources, conditioned by the consequences within the family and the effects on their employment. To achieve greater patient satisfaction, professionals need to pay particular attention to certain sites of pain and to patients' mental health. PMID- 27400417 TI - Thioflavin T: Electronic Circular Dichroism and Circularly Polarized Luminescence Induced by Amyloid Fibrils. AB - The circularly polarized luminescence (CPL) spectrum of thioflavin T (ThT) bound to insulin amyloid fibrils has been measured for the first time. It has been found that the samples exhibiting induced circular dichroism (CD) retain the optical activity in the CPL spectra, with the same sign of the rotatory strength. The fluorescence dissymmetry factor is substantial (of the order of magnitude 10( 2) ). Unlike in the corresponding CD and absorption spectra, there is no shift of the CPL band with respect to the fluorescence band. It has been verified that the measured CPL spectra are free from artifacts from circularly polarized scattering of emitted light by conducting additional measurements in a medium with a refractive index similar to insulin (methylsalicylate). The CD and CPL spectra have been interpreted by means of density functional calculations carried out for ThT in its ground and first excited states in different dielectric environments and for ThT interacting with an aromatic ring. It has been found that the presence of an aromatic ring close to the ThT molecule induces Cotton effects of the same order of magnitude as the stabilization of one enantiomeric conformer. Thus, it is expected that both mechanisms contribute to the induced CD and CPL effect to a similar degree. PMID- 27400418 TI - When vaping lobbyists get science wrong - reply to Poirson. PMID- 27400419 TI - Reversible cryo-arrest for imaging molecules in living cells at high spatial resolution. AB - The dynamics of molecules in living cells hampers precise imaging of molecular patterns by functional and super-resolution microscopy. We developed a method that circumvents lethal chemical fixation and allows on-stage cryo-arrest for consecutive imaging of molecular patterns within the same living, but arrested, cells. The reversibility of consecutive cryo-arrests was demonstrated by the high survival rate of different cell lines and by intact growth factor signaling that was not perturbed by stress response. Reversible cryo-arrest was applied to study the evolution of ligand-induced receptor tyrosine kinase activation at different scales. The nanoscale clustering of epidermal growth factor receptor (EGFR) in the plasma membrane was assessed by single-molecule localization microscopy, and endosomal microscale activity patterns of ephrin receptor A2 (EphA2) were assessed by fluorescence lifetime imaging microscopy. Reversible cryo-arrest allows the precise determination of molecular patterns while conserving the dynamic capabilities of living cells. PMID- 27400420 TI - Germ Cell Testicular Cancer Incidence, Latitude and Sunlight Associations in the United States and Australia. AB - International patterns suggest germ cell testicular cancer (GCTC) incidence may be lower in lower latitudes. To investigate this possibility, we examined GCTC incidence by latitude (population centroid in 2000) for men >=15 years within two reasonably homogeneous countries, the United States and Australia. In the United States, we examined age-adjusted incidence/latitude trends using data from states (2001-2010) and local-area registries (1980-2011). In Australia, we evaluated incidence/latitude trends in 61 Statistical Divisions (2000-2009). In U.S. White men (68 566 cases), state incidences increased by latitude, rising 5.74% (4.45 7.05%) per 5 degrees North latitude increment. Similar trends were found for seminoma and nonseminoma subtypes (P < 0.001). In U.S. Black men (2256 cases), the association was also seen (4.9%; 0.2-9.7%). In local U.S. data, similar increases in incidence with latitude were present in each of the last three decades. In Australia (6042 cases), the incidence increased by 4.43% (95% CI: 1.54-7.39%) per 5 degrees South, and trends for subtypes were similar. Thus, we found that incidence of GCTC in both White and Black men increased significantly with distance from the equator, approximately 1% per degree within the range of latitudes studied. PMID- 27400421 TI - Effects of pyrogallic acid on Microcystis aeruginosa: oxidative stress related toxicity. AB - Pyrogallic acid (PA) is used in various industrial and consumer products. The molecular mechanisms underlying PA's toxicity was not fully understood. In this study, toxicity of PA on Microcystis aeruginosa with reactive oxygen species (ROS) generation as an end point was investigated. The results showed an increase in the percentage of cells with loss of membrane integrity and enhanced intracellular ROS production. Exposure to 50mgL(-1) PA for 48h caused the highest percentage of loss of membrane integrity (56.7%), and a 2.54-fold higher intracellular ROS level compared to control. Further investigation revealed that PA caused a dose-dependent increase in DNA strand breaks (DSB) of M. aeruginosa at exposure concentration from 2 to 50mgL(-1). The incubation of cells with ROS scavengers ascorbic acid, N-acetyl-l-cysteine (NAC) and tocopherol markedly alleviated the level of PA-induced DSB. Analysis of PA autoxidized products in culture solution showed that PA was quickly converted to purpurogallin (PG), and PG was further autoxidized to other polyphenolic compounds. PA and PG might participate a futile redox cycle, which mediated ROS production in M. aeruginosa. These results suggested DNA strands and cell membrane were two targets of ROS induced by PA, and oxidative damage was an important mechanism for the toxicity of PA against M. aeruginosa. PMID- 27400422 TI - Packed-bed column biosorption of chromium(VI) and nickel(II) onto Fenton modified Hydrilla verticillata dried biomass. AB - The present study represents the first attempt to investigate the biosorption potential of Fenton modified Hydrilla verticillata dried biomass (FMB) in removing chromium(VI) and nickel(II) ions from wastewater using up-flow packed bed column reactor. Effects of different packed-bed column parameters such as bed height, flow rate, influent metal ion concentration and particle size were examined. The outcome of the column experiments illustrated that highest bed height (25cm); lowest flow rate (10mLmin(-1)), lowest influent metal concentration (5mgL(-1)) and smallest particle size range (0.25-0.50mm) are favourable for biosorption. The maximum biosorption capacity of FMB for chromium(VI) and nickel(II) removal were estimated to be 89.32 and 87.18mgg(-1) respectively. The breakthrough curves were analyzed using Bed Depth Service Time (BDST) and Thomas models. The experimental results obtained agree to both the models. Column regeneration experiments were also carried out using 0.1M HNO3. Results revealed good reusability of FMB during ten cycles of sorption and desorption. Performance of FMB-packed column in treating secondary effluent was also tested under identical experimental conditions. Results demonstrated significant reduction in chromium(VI) and nickel(II) ions concentration after the biosorption process. PMID- 27400423 TI - Duration Dependent Effects of Transcranial Pulsed Current Stimulation (tPCS) Indexed by Electroencephalography. AB - OBJECTIVE: To explore the duration of tPCS after effects given different durations of stimulation on power and interhemispheric coherence of the EEG frequency bands. Our hypothesis was that longer tPCS duration would induce a differential effect on the EEG analysis and a longer duration of after effects on the EEG frequency bands. MATERIALS AND METHODS: We conducted a double blind, sham controlled study in which forty healthy subjects were randomized to receive a single session of either 10, 20, 30 min of active (2 mA, random frequency between 6 and 10 Hz, ear clip montage) or sham tPCS. EEG was recorded before and after the intervention to assess tPCS induced after effects. RESULTS: We found that 10 and 20 min of active tPCS induced a significant increase in alpha (p = 0.004) and theta (p = 0.006) coherence in the frontal region as compared with the sham stimulation. No significant changes were found with 30 min of stimulation (p < 0.05). The Kaplan Meier analysis showed that 10 and 20 min of tPCS induced after effects that lasted 50 min. CONCLUSIONS: These results evidence the nonlinear relationship between the stimulation duration and the tPCS after effects, suggesting the presence of homeostatic mechanisms. PMID- 27400424 TI - Memory deficit, toxic effects and activity of Na(+), K(+)-ATPase and NTPDase in brain of Wistar rats submitted to orally treatment with alpha-terpinene. AB - The neurotoxic effects and activity of Na(+), K(+)-ATPase and NTPDase in Wistar rats after treatment with alpha-terpinene (daily oral administration of 0.5, 0.75 and 1.0mLkg(-1) for 10days) were examined. Results of the inhibitory avoidance task showed a memory deficit (p<0.05) in rats treated with all doses of alpha terpinene. The evaluation of DNA damage in brain tissue revealed an increase (p<0.05) on frequency of damage and damage index in all concentrations. According to the cytotoxicity assay, doses of 0.5, 0.75 and 1.0mLkg(-1) increase the lactate dehydrogenase levels, and doses of 1.0mLkg(-1) also decrease (p<0.05) cell viability in brain cells. A decrease (p<0.05) on Na(+), K(+)-ATPase activity in brain tissue and on NTPDase activity in serum were observed in all concentrations of alpha-terpinene. These results suggest that the alpha-terpinene was cytotoxic and genotoxic to the brain cells by inducing loss of cell viability and DNA damage, as well as causing alterations in Na(+), K(+)-ATPase and NTPDase activity, what may contribute to the memory deficit of treated animals. Thus, alpha-terpinene cannot be consumed by the population at the doses studied. PMID- 27400425 TI - Lipoprotein lipase and lipid profiles in plasma and placenta from normal pregnancies compared with patients with intrahepatic cholestasis of pregnancy. AB - OBJECTIVE: To analyse lipoprotein lipase (LPL) expression and lipid levels in placenta and plasma of patients with intrahepatic cholestasis of pregnancy (ICP) and normal pregnancies. METHODS: This prospective study included 30 patients with ICP and 30 gestational-age-matched pregnancies without any complications. Enzyme linked immunosorbent assays were used to investigate plasma LPL levels from 28 weeks of gestation, at 4-weekly intervals, to 38 weeks of gestation, and data were assessed longitudinally. Immunohistochemistry, Western blotting and real time polymerase chain reaction were used to detect placental LPL expression and activity. Placental triglyceride and total cholesterol levels were also analysed. The clinical data related to ICP and lipid profiles were collected retrospectively. RESULTS: Plasma LPL concentration increased with gestational age in both groups, but the increase was limited in the ICP group. Immunohistochemistry revealed LPL staining mainly in syncytiotrophoblasts, and 3,3'-diamino-benzidine tetrahydrochloride wt% was lower in ICP placenta compared with normal placenta (p<0.01). LPL protein and mRNA expression in ICP placenta were significantly lower than in normal placenta (p<0.01). LPL activity was not significantly different in both groups. Correlation analysis indicated that the plasma LPL level was negatively associated with the corresponding concentration of total bile acid (r=-0.57) in the ICP group. CONCLUSION: Reduced LPL expression in placenta, limited increase in LPL level in maternal plasma, and abnormal lipid profiles were found in patients with ICP. LPL was possibly related to ICP by participating abnormal lipid metabolism. PMID- 27400426 TI - Complexity analysis of fetal heart rate preceding intrauterine demise. AB - BACKGROUND: Visual non-stress test interpretation lacks the optimal specificity and observer-agreement of an ideal screening tool for intrauterine fetal demise (IUFD) syndrome prevention. Computational methods based on traditional heart rate variability have also been of limited value. Complexity analysis probes properties of the dynamics of physiologic signals that are otherwise not accessible and, therefore, might be useful in this context. OBJECTIVE: To explore the association between fetal heart rate (FHR) complexity analysis and subsequent IUFD. Our specific hypothesis is that the complexity of the fetal heart rate dynamics is lower in the IUFD group compared with controls. STUDY DESIGN: This case-control study utilized cases of IUFD at a single tertiary-care center among singleton pregnancies with at least 10min of continuous electronic FHR monitoring on at least 2 weekly occasions in the 3 weeks immediately prior to fetal demise. Controls delivered a live singleton beyond 35 weeks' gestation and were matched to cases by gestational age, testing indication, and maternal age in a 3:1 ratio. FHR data was analyzed using the multiscale entropy (MSE) method to derive their complexity index. In addition, pNNx, a measure of short-term heart rate variability, which in adults is ascribable primarily to cardiac vagal tone modulation, was also computed. RESULTS: 211 IUFDs occurred during the 9-year period of review, but only 6 met inclusion criteria. The median gestational age at the time of IUFD was 35.5 weeks. Three controls were matched to each case for a total of 24 subjects, and 87 FHR tracings were included for analysis. The median gestational age at the first fetal heart rate tracing was similar between groups (median [1st-3rd quartiles] weeks: IUFD cases: 34.7 (34.4-36.2); controls: 35.3 (34.4-36.1); p=.94). The median complexity of the cases' tracings was significantly less than the controls' (12.44 [8.9-16.77] vs. 17.82 [15.21-22.17]; p<.0001). Furthermore, the cases' median complexity decreased as gestation advanced whereas the controls' median complexity increased over time. However, this difference was not statistically significant [-0.83 (-2.03 to 0.47) vs. 0.14 (-1.25 to 0.94); p=.62]. The degree of short-term variability of FHR tracings, as measured by the pNN metric, was significantly lower (p<.005) for the controls (1.1 [0.8-1.3]) than the IUFD cases (1.3 [1.1-1.6]). CONCLUSIONS: FHR complexity analysis using multiscale entropy analysis may add value to other measures in detecting and monitoring pregnancies at the highest risk for IUFD. The decrease in complexity and short-term variability seen in the IUFD cases may reflect perturbations in neuroautonomic control due to multiple maternal-fetal factors. PMID- 27400428 TI - Glycomics: New Challenges and Opportunities in Regenerative Medicine. AB - Tissue engineering relies on the possibility to engineer cell microenvironments by means of bioactive materials, biochemical and physical stimuli in order to guide cell behaviour and to regenerate damaged tissue. Despite the relevance of glycan epitopes as signaling molecules, and the recent advances in glycomics, their use as biomolecular cues at the interface between materials and cells for the controlled stimulation of adhesion and differentiation processes for regenerative medicine applications is still limited. In this concept article we will briefly outline the basis and the impact on health and economics of regenerative medicine, together with the recent applications of the glycocode in tissue regeneration approaches. PMID- 27400429 TI - Reply: Stryker SMARTLock Hybrid Maxillomandibular Fixation System: Clinical Application, Complications, and Radiographic Findings. PMID- 27400430 TI - Reply: Surgical Treatment of Facial Infantile Hemangiomas: An Analysis Based on Tumor Characteristics and Outcomes. PMID- 27400431 TI - Stryker SMARTLock Hybrid Maxillomandibular Fixation System: Clinical Application, Complications, and Radiographic Findings. PMID- 27400432 TI - Lengthening Temporalis Myoplasty for Single-Stage Smile Reconstruction in Children with Facial Paralysis. PMID- 27400433 TI - Surgical Treatment of Facial Infantile Hemangiomas: An Analysis Based on Tumor Characteristics and Outcomes. PMID- 27400434 TI - Time Required to Initiate a Defensive Reaction to Direct and Feint Attacks in Fencing. AB - The two-fold purpose of this study was to analyze the time required by a fencer to initiate a defensive action in response to a direct attack, which involves identifying when the defending fencer detects the just-noticeable difference, and, secondly, to assess the effect that an attacker's rapid armed hand movement (feint attack) has on the time required to initiate a defensive move. Twenty-four elite fencers and a fencing master were included in the study. Four adapted force plates were installed on a scaffold used as a fencing piste. A 3D video analysis system recorded the location of 2 markers installed on the fencing master's shoulder and sword. The results confirm that the defending fencer has a mean movement time of 0.353 +/- 0.028 s to perform the defensive action, which provides an advantage over the attacking fencer. The velocity of movement in the peripheral visual field has no influence on the time required by elite fencers to initiate a defensive action. This confirms the crucial role that response inhibition processes play when nonrelevant actions are perceived. Kinematic analysis of markers suggests that the eye movements of elite fencers are not the only source of information used while observing an attack. PMID- 27400435 TI - Sex Differences in Physician Salary in US Public Medical Schools. AB - IMPORTANCE: Limited evidence exists on salary differences between male and female academic physicians, largely owing to difficulty obtaining data on salary and factors influencing salary. Existing studies have been limited by reliance on survey-based approaches to measuring sex differences in earnings, lack of contemporary data, small sample sizes, or limited geographic representation. OBJECTIVE: To analyze sex differences in earnings among US academic physicians. DESIGN, SETTING, AND PARTICIPANTS: Freedom of Information laws mandate release of salary information of public university employees in several states. In 12 states with salary information published online, salary data were extracted on 10 241 academic physicians at 24 public medical schools. These data were linked to a unique physician database with detailed information on sex, age, years of experience, faculty rank, specialty, scientific authorship, National Institutes of Health funding, clinical trial participation, and Medicare reimbursements (proxy for clinical revenue). Sex differences in salary were estimated after adjusting for these factors. EXPOSURES: Physician sex. MAIN OUTCOMES AND MEASURES: Annual salary. RESULTS: Among 10 241 physicians, female physicians (n = 3549) had lower mean (SD) unadjusted salaries than male physicians ($206 641 [$88 238] vs $257 957 [$137 202]; absolute difference, $51 315 [95% CI, $46 330-$56 301]). Sex differences persisted after multivariable adjustment ($227 783 [95% CI, $224 117-$231 448] vs $247 661 [95% CI, $245 065-$250 258] with an absolute difference of $19 878 [95% CI, $15 261-$24 495]). Sex differences in salary varied across specialties, institutions, and faculty ranks. For example, adjusted salaries of female full professors ($250 971 [95% CI, $242 307-$259 635]) were comparable to those of male associate professors ($247 212 [95% CI, $241 850-$252 575]). Among specialties, adjusted salaries were highest in orthopedic surgery ($358 093 [95% CI, $344 354-$371 831]), surgical subspecialties ($318 760 [95% CI, $311 030-$326 491]), and general surgery ($302 666 [95% CI, $294 060-$311 272]) and lowest in infectious disease, family medicine, and neurology (mean income, <$200 000). Years of experience, total publications, clinical trial participation, and Medicare payments were positively associated with salary. CONCLUSIONS AND RELEVANCE: Among physicians with faculty appointments at 24 US public medical schools, significant sex differences in salary exist even after accounting for age, experience, specialty, faculty rank, and measures of research productivity and clinical revenue. PMID- 27400437 TI - Topiramate Overcoming Dopamine Agonist-Induced Migraine Exacerbation and Avoiding Transsphenoidal Surgery in a Young Boy With a Macroprolactinoma. PMID- 27400438 TI - Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis. AB - OBJECTIVES: To investigate cross-sectional associations between serum levels of resistin and interleukin-17 (IL-17) and cartilage defects and bone marrow lesions (BMLs) in patients with knee symptomatic osteoarthritis (OA). METHODS: One hundred and ninety-four consecutively-selected patients with knee symptomatic OA (mean 55.4 years, range 34-74, 87% females) were included in Anhui Osteoarthritis (AHOA) Study. Knee cartilage defects and BMLs were determined at different sites using T2-weighted fat-suppressed fast spin echo MRI. Serum resistin, IL-17, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA. RESULTS: In multivariable analyses, serum resistin was positively associated with cartilage defects at lateral femoral, lateral tibial, and medial tibial (all p < 0.05) sites. The significant associations were also present with BMLs at lateral femoral and tibial sites (ORs: 1.13-1.19, both p < 0.05). In patients with the highest quartile of hs-CRP (>2.45 pg/ml), IL-17 was positively and significantly associated with cartilage defect score at nearly all sites (ORs: 1.33-1.44, all p < 0.05), and BMLs at lateral and medial femoral sites (ORs: 1.26-1.51, both p < 0.05). CONCLUSIONS: Serum levels of resistin were positively and independently associated with cartilage defects and BMLs in patients with knee OA. Serum IL-17 was significantly associated with cartilage defects and BMLs in patients with an increased inflammatory status. These suggest that metabolic and inflammatory mechanisms may have a role to play in knee OA. PMID- 27400439 TI - Using emergency department surveillance data to assess occupational injury and illness reporting by workers. AB - OBJECTIVE: Researchers from the National Institute for Occupational Safety and Health (NIOSH) share detailed methodologies from conducting two follow-back studies initiated in 2010 that were designed to assess whether workers reported their injuries and illnesses to their employers and to identify worker incentives and disincentives for reporting work-related injuries to employers. METHODOLOGY: Study respondents were sampled from the National Electronic Injury Surveillance System occupational supplement (NEISS-Work), an emergency department-based surveillance system. Telephone interviews were used to collect information directly from workers. OUTCOMES: Among persons treated in emergency departments who could be identified as working at the time of injury or illness, most reported their injury or illness to their employer. Our studies did not assess if these reported injuries and illnesses were recorded on the Occupational Safety and Health logs. DISCUSSION: Our approach suggests that emergency department based surveillance data are limited in their utility to investigate underreporting among workers. Am. J. Ind. Med. 59:600-609, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400436 TI - Higher order signaling: ARL2 as regulator of both mitochondrial fusion and microtubule dynamics allows integration of 2 essential cell functions. AB - ARL2 is among the most highly conserved proteins, predicted to be present in the last eukaryotic common ancestor, and ubiquitously expressed. Genetic screens in multiple model organisms identified ARL2, and its cytosolic binding partner cofactor D (TBCD), as important in tubulin folding and microtubule dynamics. Both ARL2 and TBCD also localize to centrosomes, making it difficult to dissect these effects. A growing body of evidence also has found roles for ARL2 inside mitochondria, as a regulator of mitochondrial fusion. Other studies have revealed roles for ARL2, in concert with its closest paralog ARL3, in the traffic of farnesylated cargos between membranes and specifically to cilia and photoreceptor cells. Details of each of these signaling processes continue to emerge. We summarize those data here and speculate about the potential for cross-talk or coordination of cell regulation, termed higher order signaling, based upon the use of a common GTPase in disparate cell functions. PMID- 27400440 TI - Characterizing emergency department patients who reported work-related injuries and illnesses. AB - BACKGROUND: Per a Congressional directive and funding, this study describes worker and workplace characteristics of emergency department (ED) patients who reported their injury/illness to their employer. The study also responds to Congress's request to enumerate injured/ill self-employed workers and workers with chronic conditions. METHODS: We conducted a follow-back study on injured/ill workers, including self-employed, identified from a national ED surveillance system from June 2012 through December 2013. RESULTS: An estimated 3,357,000 (95%CI: 2,516,000-4,199,000) workers treated in EDs reported their injury/illness to their employer or were self-employed. Of those, 202,000 (95%CI: 133,000 272,000) had a chronic condition. Of all reporters, excluding self-employed, 77% indicated they received instructions as to whom to report. CONCLUSION: The study did not identify underreporting issues and revealed that medical records data may not be appropriate for assessing underreporting. Additional research is needed to examine workplace characteristics that encourage injury and illness reporting. Am. J. Ind. Med. 59:610-620, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400441 TI - Reported work-related injuries and illnesses among Hispanic workers: Results from an emergency department surveillance system follow-back survey. AB - BACKGROUND: Research suggests Hispanic workers underreport injuries/illnesses to their employer. METHODS: The National Electronic Injury Surveillance System occupational supplement was used to conduct a follow-back study of workers treated in emergency departments (EDs) from June 2012 through December 2013. RESULTS: An estimated 448,000 (95%CI 230,000-665,000) Hispanic workers treated in EDs for a work-related injury or illness were represented by 362 completed interviews. Of these, an estimated 443,000 (95%CI 228,000-657,000) workers reported the injury or illness to their employer or were self-employed. The majority had not heard of workers' compensation. Only 10% expected workers' compensation to cover their medical payment while 62% expected payment to be covered by their employer. CONCLUSION: We characterized our respondent workforce who reported their injury or illness. We determined that NEISS-Work data are not the most appropriate source to capture underreporting of work-related injuries and illnesses to employers among Hispanic workers. Am. J. Ind. Med. 59:621-629, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400442 TI - Hired farmworkers in the US: Demographics, work organisation, and services. AB - OBJECTIVE: Farm work is labor-intensive, physically demanding, and incurs a high risk of injury. The aim of this study was to identify characteristics of farmworkers at increased risk of adverse health outcomes to focus targeted interventions. METHODS: The National Agricultural Workers Survey for 2008-2012 was used to compare characteristics associated with adverse health and safety conditions among US-born and Mexican and Central American-born Latino and Indigenous, documented and undocumented farmworkers, separately for males and females. RESULTS: US-born farmworkers had more secure work, worked less onerous tasks, and earned more per hour than other categories of farmworkers. Undocumented Indigenous workers had more precarious work, worked more onerous tasks, and were more likely to do piece work, than undocumented Latino workers. DISCUSSION: We highlight disparities in modifiable occupational health risk factors across groups of farmworkers that are associated with increased risks of work-related injury and poor health. Am. J. Ind. Med. 59:644-655, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400443 TI - Obesity indices are predictive of elevated C-reactive protein in long-haul truck drivers. AB - BACKGROUND: Obesity rates in long-haul truck drivers have been shown to be significantly higher than the general population. We hypothesized that commercial drivers with the highest levels of general obesity and abdominal adiposity would have higher concentrations of high sensitivity C-reactive protein (CRP), a marker of inflammation. METHODS: Survey and anthropometric data were collected from 262 commercial drivers. Weight, circumference measures, and blood analysis for CRP (N = 115) were conducted and compared to National Health and Nutrition Examination Survey (NHANES) data. CRP values were non-normally distributed and logarithmically transformed for statistical analyses. RESULTS: BMI, waist circumference, sagittal abdominal diameter, and CRP were significantly higher than in the general population. Anthropometric indices that included height (BMI, waist-to-height ratio, and sagittal diameter-to-height ratio), were most predictive of CRP values. CONCLUSIONS: Abdominal obesity is prevalent in commercial vehicle drivers and is an important indicator of the presence of inflammation in this population. Am. J. Ind. Med. 59:665-675, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400444 TI - Biophysical insights into the interaction of hen egg white lysozyme with therapeutic dye clofazimine: modulation of activity and SDS induced aggregation of model protein. AB - The present study details the binding process of clofazimine to hen egg white lysozyme (HEWL) using spectroscopy, dynamic light scattering, transmission electron microscopy (TEM), and molecular docking techniques. Clofazimine binds to the protein with binding constant (Kb) in the order of 1.57 * 104 at 298 K. Binding process is spontaneous and exothermic. Molecular docking results suggested the involvement of hydrogen bonding and hydrophobic interactions in the binding process. Bacterial cell lytic activity in the presence of clofazimine increased to more than 40% of the value obtained with HEWL only. Interaction of the drug with HEWL induced ordered secondary structure in the protein and molecular compaction. Clofazimine also effectively inhibited the sodium dodecyl sulfate (SDS) induced amyloid formation in HEWL and caused disaggregation of preformed fibrils, reinforcing the notion that there is involvement of hydrophobic interactions and hydrogen bonding in the binding process of clofazimine with HEWL and clofazimine destabilizes the mature fibrils. Further, TEM images confirmed that fibrillar species were absent in the samples where amyloid induction was performed in the presence of clofazimine. As clofazimine is a drug less explored for the inhibition of fibril formation of the proteins, this study reports the inhibition of SDS-induced amyloid formation of HEWL by clofazimine, which will help in the development of clofazimine-related molecules for the treatment of amyloidosis. PMID- 27400445 TI - The use of conformationally thermostabilised GPCRs in drug discovery: application to fragment, structure and biophysical techniques. AB - Recent developments in receptor stabilisation have facilitated major advances in G protein-coupled receptor (GPCR) research, notably structural biology, over the past eight years. Here we review the application of fragment, structure and biophysical techniques using stabilised GPCRs (StaR proteins), and their impact in the drug discovery process. These techniques have, most recently, been utilised in the discovery of the non-alkyne mGlu5 negative allosteric modulator HTL14242, in addition to the dual orexin receptor antagonist HTL6641, with differentiated residence time kinetics. PMID- 27400446 TI - High prevalence of vitamin D deficiency in women with breast cancer: The first Chilean study. AB - BACKGROUND: Breast cancer (BC) is the leading cause of female death from malignancy worldwide. One factor that has been associated to a higher incidence and poor prognosis is a Vitamin D deficiency (measured as 25-Hydroxi-Vitamin D (25OHD)). Our aim was to determine 25OHD levels in serum samples of Chilean BC patients before endocrine therapy and its association to clinical parameters at the time of diagnosis. METHODS: We analyzed clinical records of 105 women, evaluated at the Cancer Center of the Pontificia Universidad Catolica de Chile. Serum levels of 25OHD were determined using a chemiluminescent microparticle immunoassay. RESULTS: The prevalence of vitamin D deficiency before endocrine therapy was of 70.5%. Only 7% of our patients showed sufficient vitamin D levels at the beginning of the endocrine treatment. There was a significant correlation found between age and 25OHD levels, and also between body fat percentage and 25OHD levels (r(2) = 0.04; p = 0.021; r(2) = 0.028; p = 0.0432, respectively). Summer 25OHD levels were significantly higher than winter levels (p = 0.0322). CONCLUSION: Vitamin D deficiency is highly prevalent in Chilean BC women before endocrine therapy and 25OHD levels are inversely correlated to the age and body fat percentage of patients. Further studies are needed to determine causal relationship between vitamin D levels and BC development and outcome. PMID- 27400447 TI - Surrogate end points for overall survival in breast cancer trials: A review. AB - Our aim was to review the studies which assessed potential surrogate endpoints for overall survival (OS) in breast cancer trials. A Literature search in PubMed database of studies which assessed potential surrogate endpoints for OS in breast cancer trials was conducted. The surrogacy was assessed with the German institute of Quality and efficiency in Health Care's (IWQiG) framework and the Fleming hierarchy. Thirteen studies were identified. At the neoadjuvant setting, two individual patient data (IPD) meta-analyses and one aggregate data meta-analysis assessing surrogacy of pathological complete response (PCR) were identified. Trial-level association was calculated in one study and the squared correlation was 0.24. Therefore PCR was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the adjuvant setting, one meta-analysis on aggregate data was identified. 2-year DFS was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the metastatic setting, six meta-analyses based on aggregate data, three IPD meta-analyses and one retrospective study were identified. Within the IPD meta-analyses, at the trial-level association the squared correlation between the potential surrogates and OS ranged from 0.10 to 0.57 and no endpoint was judged to be valid surrogate for OS at the metastatic setting. The level of evidence available supporting a relationship between OS and potential surrogate endpoints in breast cancer trials is low. PMID- 27400448 TI - Current treatment of dyslipidaemia: PCSK9 inhibitors and statin intolerance. AB - Statins are the cornerstone of the management of dyslipidaemias and prevention of cardiovascular disease. Although statins are, overall, safe and well tolerated, adverse events can occur and constitute an important barrier to maintaining long term adherence to statin treatment. In patients who cannot tolerate statins, alternative treatments include switch to another statin, intermittent-dosage regimens and non-statin lipid-lowering medications. Nonetheless, a high proportion of statin-intolerant patients are unable to achieve recommended low density lipoprotein (LDL) cholesterol goals, thereby resulting in substantial residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease implicated in LDL receptor degradation and plays a central role in cholesterol metabolism. In recent studies, PCSK9 inhibition by means of monoclonal antibodies achieved LDL cholesterol reductions of 50% to 70% across various patient populations and background lipid-lowering therapies, while maintaining a favourable safety profile. The efficacy and safety of the monoclonal antibodies alirocumab and evolocumab were confirmed in statin intolerant patients, indicating that PCSK9 inhibitors represent an attractive treatment option in this challenging clinical setting. PCSK9 inhibitors recently received regulatory approval for clinical use and may be considered in properly selected patients according to current consensus documents, including patients with statin intolerance. In this review we summarise current evidence regarding diagnostic evaluation of statin-related adverse events, particularly statin associated muscle symptoms, and we discuss current recommendations on the management of statin-intolerant patients. In view of emerging evidence of the efficacy and safety of PCSK9 inhibitors, we further discuss the role of monoclonal PCSK9 antibodies in the management of statin-intolerant hypercholesterolaemic patients. PMID- 27400449 TI - Prevalence, characteristics, and acute care utilization of disabled older adults with an absence of help for activities of daily living: Findings from a nationally representative survey. AB - OBJECTIVE: The aim of this study was to investigate the prevalence, characteristics, and acute care utilization of community dwelling disabled older adults with an absence of help for activities of daily living (ADL). METHODS: We analyzed cross-sectional data from a nationally representative sample of people aged 65 years and over (n=2904) participating in the 2009 National Health Interview Survey in Taiwan. Disability was defined as self-reporting a lot of difficulty or complete inability to carry out one or more ADL tasks. Participants with disability were asked whether they received help in the form of personal assistance or assistive devices to complete ADL tasks, with a yes response indicating the presence of help and a no response indicating the absence of help. Hospitalization and emergency department visits was assessed as a dichotomous variable (any or none), respectively. RESULTS: An absence of available help for ADL disability was reported in 16.6% of disabled older adults. Disabled older adults reporting an absence of help were more likely to be female. After adjustment for other factors, compared to older adults without disability, older adults with disability not receiving help for ADL tasks were highly related to hospitalization (OR=4.57; 95%CI=[1.51-13.82]) and emergency department visits (OR=3.52; 95%CI=[1.15-10.76]) during the past year, respectively. CONCLUSIONS: We found that there is high prevalence of absence of help to perform ADL tasks in older adults with disability, and that this absence of help for ADL disability is associated with a greater burden of acute care utilization than those without disability. PMID- 27400450 TI - Quality of standing balance in community-dwelling elderly: Age-related differences in single and dual task conditions. AB - AIM: To examine the relationship between age and quality of standing balance in single and dual task conditions. METHODS: A cross-sectional study was conducted using a sample of 243 community-dwellers aged >=65 years. Quality of standing balance was assessed by measuring the center of pressure (COP) sway with a pressure platform. Measurements were performed under single task (orthostatic position) and dual task (orthostatic position while performing a verbal fluency task) conditions. RESULTS: The mean age of the participants was 79.1(+/-7.3)years and 76.1% were women. Older age was associated with an increased COP sway, mainly in the medial/lateral (ML) direction. Most COP sway parameters were higher under dual task conditions than under single task. After controlling for the effect of the number of words enunciated in dual task conditions, only the differences in COP sway parameters in the ML direction remained significant. There was no significant interaction between age group (65-79; >=80 years) and condition, which indicates that differences in COP sway caused by performing a secondary task were similar for younger and for older participants. CONCLUSION: Age did not seem to influence significantly the decline in the quality of standing balance triggered by performing a concurrent cognitive task. However, older age was consistently associated with poorer standing balance, both in single and in dual task conditions. Therefore, performing a secondary task may lead older individuals to reach their postural stability limits and, consequently, to fall. PMID- 27400451 TI - Production of staphylococcal enterotoxins in microbial broth and milk by Staphylococcus aureus strains harboring seh gene. AB - Twenty Staphylococcus aureus strains harboring seh gene, including one carrying also sec gene and 11 sea gene, were grown in BHI+YE broth and milk and were tested for SEA, SEC and SEH production. All strains decreased pH of BHI+YE broth at 24h and increased them at 48h. Seventeen S. aureus strains grown in milk changed pH for no >0.3 unit until 48h. Three other S. aureus strains significantly decreased pH during growth in milk. All S. aureus produced SEH in BHI+YE broth in amounts ranging from 95 to 1292ng/ml, and from 170 to 4158ng/ml at 24 and 48h, respectively. SEH production in milk by 17 strains did not exceed 23ng/ml at 24h and 36ng/ml at 48h. Three S. aureus strains able to decrease milk pH produced 107-3029ng/ml and 320-4246ng/ml of SEH in milk at 24 and 48h, respectively. These strains were grown in milk and BHI+YE broth with pH stabilized at values near neutral leading to a significant decrease of SEH production. Representative weak SEH producers were grown in milk at reduced pH resulting in moderate increase in SEH production. SEA was produced in milk by 10S. aureus strains at 24-151ng/ml at 24h, and 31-303ng/ml at 48h. SEA production in milk was higher or comparable as in BHI+YE broth in 3 strains and lower for remaining strains. Production of SEC by sec-positive S. aureus strains was lower in milk than in BHI+YE broth, ranging from 131 to 2319ng/ml at 24 and 48h in milk and 296-30,087ng/ml in BHI+YE at 24 and 48h. Both lacE and lacG transcripts involved in lactose metabolism were significantly up-regulated in milk in strong SEH producers. In these strains hld, rot and sarA transcripts were up-regulated in milk as compared to weak SEH producers. Stabilization of milk pH at a value of raw milk significantly down-regulated hld, rot and sarA RNA in strong SEH producers. Milk was generally found unfavorable for enterotoxin production. However, certain S. aureus strains were not restricted in SEH and SEA expression in milk, unlike SEC which remained down-regulated in this environment. Therefore, low safety risk related to S. aureus producing SEC in milk, as suggested previously, may not pertain to certain SEA and SEH-producing strains. PMID- 27400452 TI - Arginine acts as an inhibitor of the biosynthesis of several mycotoxins. AB - It is well known that the type and the availability of nitrogen have a great influence on the biosynthesis of certain mycotoxins. Here it is shown that some amino acids have no influence, some others strongly support and a third group inhibits the biosynthesis of ochratoxin (OTA) by Penicillium nordicum even in a complex medium, such as PDA. Arginine (Arg) is one of the strong OTA inhibiting amino acids. It was shown that Arg not only inhibits OTA in Penicillium but also citrinin (CIT) biosynthesis in Penicillium verrucosum, Penicillium expansum and Penicillium citrinum and alternariol (AOH), alternariol monomethylether (AME) and tenuazonic acid (TeA) biosynthesis in Alternaria alternata. The minimal inhibitory concentration of Arg differs depending on the mycotoxin and the species analysed. However, the OTA biosynthesis by P. verrucosum and P. nordicum was most sensitive. Growth, on the other hand, was much less affected by Arg. Urea, a metabolite of Arg catabolism, shows a similar inhibitory activity. In wheat medium containing 50mM Arg almost no OTA was produced by Penicillium, in contrast to plain wheat medium. PMID- 27400453 TI - Lactic acid bacteria as protective cultures in fermented pork meat to prevent Clostridium spp. growth. AB - In meat fermented foods, Clostridium spp. growth is kept under control by the addition of nitrite. The growing request of consumers for safer products has led to consider alternative bio-based approaches, the use of protective cultures being one of them. This work is aimed at checking the possibility of using two Lactobacillus spp. strains as protective cultures against Clostridium spp. in pork ground meat for fermented salami preparation. Both Lactobacillus strains displayed anti-clostridia activity in vitro using the spot agar test and after co culturing them in liquid medium with each Clostridium strain. Only one of them, however, namely L. plantarum PCS20, was capable of effectively surviving in ground meat and of performing anti-microbial activity in carnis in a challenge test where meat was inoculated with the Clostridium strain. Therefore, this work pointed out that protective cultures can be a feasible approach for nitrite reduction in fermented meat products. PMID- 27400454 TI - Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach. AB - IMPORTANCE: Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units. However, not all patients with an HD phenotype carry the pathological expansion in HTT, and the positive diagnosis rate is poor. OBJECTIVES: To examine patients with HD phenotypes to determine the frequency of HD phenocopies with typical features of HD but without pathological CAG repeat expansions in HTT in an attempt to improve the positive diagnosis rate. DESIGN, SETTING, AND PARTICIPANTS: Between January 1, 2004, and April 18, 2011, a total of 226 consecutive index patients with an HD phenotype were referred to specialized clinics of the French National Huntington Disease Reference Centre for Rare Diseases. They underwent detailed clinical examination and follow-up, as well as neuropsychological, biological, imaging, and genetic examinations. Nucleotide expansions in JPH3, ATN1, TBP, and C9ORF72 and mutations in PRNP, as well as acquired conditions commonly causing HD phenocopies, were first screened. MAIN OUTCOMES AND MEASURES: The diagnostic rate of HD phenocopies and frequency of other etiologies using deep clinical phenotyping and next generation sequencing. Our goal was to improve the genetic diagnosis of HD phenocopies and to identify new HD related genes. RESULTS: One hundred ninety-eight patients carried a pathological CAG repeat expansion in HTT, whereas 28 patients (12 women and 16 men) did not. Huntington disease phenocopies accounted for 12.4%, and their mean (SD) age at onset was similar to those of the HD-HTT group (47.3 [12.7] years vs 50.3 [16.4] years, P = .29). We first identified 3 patients with abnormal CTG expansions in JPH3, a fourth patient with an antiphospholipid syndrome, and a fifth patient with B12 avitaminosis. A custom made 63-gene panel was generated based on clinical evolution and exome sequencing. It contained genes responsible for HD phenocopies and other neurodegenerative conditions, as well as candidate genes from exome sequencing in 3 index cases with imaging features of brain iron accumulation. We identified mutations in genes associated with neurodegeneration, including CACNA1A (n = 2), VPS13A (n = 1), UBQLN2 (n = 1), and VCP (n = 1). CONCLUSIONS AND RELEVANCE: Huntington disease phenocopies without CAG repeat expansions in HTT are not rare, occurring in 12.4% (28 of 226) herein, and should be considered in genetic counseling. We used next-generation sequencing combined with clinical data and disease evolution to explore multiple etiologies simultaneously. Our combined clinical and genetic exploration of 28 HD phenocopies identified the underlying cause in 35.7% (10 of 28). In conclusion, the etiologies of HD phenocopies are heterogeneous, and clinical evolution should be taken into account when searching for a genetic cause. The panel of candidate genes to be examined is larger than expected but can be guided by specific imaging and clinical features. Other neurodegenerative diseases with late onset in which variant segregation cannot be verified could be productively explored with the combined approach illustrated herein. PMID- 27400455 TI - Ultraviolet fluorescence of coelenteramide and coelenteramide-containing fluorescent proteins. Experimental and theoretical study. AB - Coelenteramide-containing fluorescent proteins are products of bioluminescent reactions of marine coelenterates. They are called 'discharged photoproteins'. Their light-induced fluorescence spectra are variable, depending considerably on external conditions. Current work studies a dependence of light-induced fluorescence spectra of discharged photoproteins obelin, aequorin, and clytin on excitation energy. It was demonstrated that photoexcitation to the upper electron excited states (260-300nm) of the discharged photoproteins initiates a fluorescence peak in the near UV region, in addition to the blue-green emission. To characterize the UV fluorescence, the light-induced fluorescence spectra of coelenteramide (CLM), fluorophore of the discharged photoproteins, were studied in methanol solution. Similar to photoproteins, the CLM spectra depended on photoexcitation energy; the additional peak (330nm) in the near UV region was observed in CLM fluorescence at higher excitation energy (260-300nm). Quantum chemical calculations by time depending method with B3LYP/cc-pVDZ showed that the conjugated pyrazine-phenolic fragment and benzene moiety of CLM molecule are responsible for the additional UV fluorescence peak. Quantum yields of CLM fluorescence in methanol were 0.028+/-0.005 at 270-340nm photoexcitation. A conclusion was made that the UV emission of CLM might contribute to the UV fluorescence of the discharged photoproteins. The study develops knowledge on internal energy transfer in biological structures - complexes of proteins with low-weight aromatic molecules. PMID- 27400456 TI - Muscle Fatigue Assessment During Cycle Ergometer Exercise Using Principal Component Analysis of Electromyogram Power Spectra. AB - During muscle fatigue analysis some standard indexes are calculated from the surface electromyogram (EMG) as root mean square value (RMS), mean (Fmean), and median power frequency (Fmedian). However, these parameters present limitations and principal component analysis (PCA) appears to be an adequate alternative. In this context, we propose two indexes based on PCA to enhance the quantitative muscle fatigue analysis during cyclical contractions. Signals of vastus lateralis muscle were collected during a maximal exercise test. Twenty-four subjects performed the test starting at 12.5 W power output with increments of 12.5 W?min 1, maintaining cadence of 50 rpm until voluntary exhaustion. The epochs of myoelectric activation were identified and used to estimate the power spectra. PCA was then applied to the power spectra of each subject. The standard (ST) and Euclidean (ED) distances were employed to estimate the alteration occurred due to fatigue. For comparison, the standard indexes were calculated. ST, ED, and RMS value were adequate for muscle fatigue analysis. Among these parameters, ST was more sensitive with higher effect size. Moreover, the Fmean and Fmedian were not sensitive to fatigue. The proposed method based on PCA of EMG in frequency domain allowed producing fatigue indexes suitable for cyclical contractions. PMID- 27400457 TI - Information or resolution: Which is required from an SEM to study bulk inorganic materials? AB - Significant technological advances in scanning electron microscopy (SEM) have been achieved over the past years. Different SEMs can have significant differences in functionality and performance. This work presents the perspectives on selecting an SEM for research on bulk inorganic materials. Understanding materials demands quantitative composition and orientation information, and informative and interpretable images that reveal subtle differences in chemistry, orientation/structure, topography, and electronic structure. The capability to yield informative and interpretable images with high signal-to-noise ratios and spatial resolutions is an overall result of the SEM system as a whole, from the electron optical column to the detection system. The electron optical column determines probe performance. The roles of the detection system are to capture, filter or discriminate, and convert signal electrons to imaging information. The capability to control practical operating parameters including electron probe size and current, acceleration voltage or landing voltage, working distance, detector selection, and signal filtration is inherently determined by the SEM itself. As a platform for various accessories, e.g. an energy-dispersive spectrometer and an electron backscatter diffraction detector, the properties of the electron optical column, specimen chamber, and stage greatly affect the performance of accessories. Ease-of-use and ease-of-maintenance are of practical importance. It is practically important to select appropriate test specimens, design suitable imaging conditions, and analyze the specimen chamber geometry and dimensions to assess the overall functionality and performance of an SEM. For an SEM that is controlled/operated with a computer, the stable software and user friendly interface significantly improve the usability of the SEM. SCANNING 38:864-879, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400458 TI - Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period. AB - IMPORTANCE: Chronic opioid use imposes a substantial burden in terms of morbidity and economic costs. Whether opioid-naive patients undergoing surgery are at increased risk for chronic opioid use is unknown, as are the potential risk factors for chronic opioid use following surgery. OBJECTIVE: To characterize the risk of chronic opioid use among opioid-naive patients following 1 of 11 surgical procedures compared with nonsurgical patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of administrative health claims to determine the association between chronic opioid use and surgery among privately insured patients between January 1, 2001, and December 31, 2013. The data concluded 11 surgical procedures (total knee arthroplasty [TKA], total hip arthroplasty, laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, cesarean delivery, functional endoscopic sinus surgery [FESS], cataract surgery, transurethral prostate resection [TURP], and simple mastectomy). Multivariable logistic regression analysis was performed to control for possible confounders, including sex, age, preoperative history of depression, psychosis, drug or alcohol abuse, and preoperatice use of benzodiazepines, antipsychotics, and antidepressants. EXPOSURES: One of the 11 study surgical procedures. MAIN OUTCOMES AND MEASURES: Chronic opioid use, defined as having filled 10 or more prescriptions or more than 120 days' supply of an opioid in the first year after surgery, excluding the first 90 postoperative days. For nonsurgical patients, chronic opioid use was defined as having filled 10 or more prescriptions or more than 120 days' supply following a randomly assigned "surgery date." RESULTS: The study included 641 941 opioid-naive surgical patients (169 666 men; mean [SD] age, 44.0 [12.8] years), and 18 011 137 opioid naive nonsurgical patients (8 849 107 men; mean [SD] age, 42.4 [12.6] years). Among the surgical patients, the incidence of chronic opioid in the first preoperative year ranged from 0.119% for Cesarean delivery (95% CI, 0.104% 0.134%) to 1.41% for TKA (95% CI, 1.29%-1.53%) The baseline incidence of chronic opioid use among the nonsurgical patients was 0.136% (95% CI, 0.134%-0.137%). Except for cataract surgery, laparoscopic appendectomy, FESS, and TURP, all of the surgical procedures were associated with an increased risk of chronic opioid use, with odds ratios ranging from 1.28 (95% CI, 1.12-1.46) for cesarean delivery to 5.10 (95% CI, 4.67-5.58) for TKA. Male sex, age older than 50 years, and preoperative history of drug abuse, alcohol abuse, depression, benzodiazepine use, or antidepressant use were associated with chronic opioid use among surgical patients. CONCLUSIONS AND RELEVANCE: In opioid-naive patients, many surgical procedures are associated with an increased risk of chronic opioid use in the postoperative period. A certain subset of patients (eg, men, elderly patients) may be particularly vulnerable. PMID- 27400459 TI - Smart Hydrogel-Based Valves Inspired by the Stomata in Plants. AB - We report the design of hydrogels that can act as "smart" valves or membranes. Each hydrogel is engineered with a pore (about 1 cm long and <1 mm thick) that remains closed under ambient conditions but opens under specific conditions. Our design is inspired by the stomatal valves in plant leaves, which regulate the movement of water and gases in and out of the leaves. The design features two different gels, active and passive, which are attached concentrically to form a disc-shaped hybrid film. The pore is created in the central active gel, and the conditions for opening the pore can be tuned based on the chemistry of this gel. For example, if the active gel is made from N-isopropylacrylamide (NIPA), the actuation of the pore depends on the temperature of water relative to 32 degrees C, which is the lower-critical solution temperature (LCST) of NIPA. The concentric design of our hybrid provides directionality to the volumetric transition of the active gel, i.e., it ensures that the pore opens as the active gel shrinks. In turn, contact with hot water (T > 32 degrees C) opens the pore and allows the water to pass through the gel. Conversely, the pore remains closed when the water is cold (T < 32 degrees C). The gel thereby acts as a "smart" valve that is able to regulate the flow of solvent depending on its properties. We have extended the concept to other stimuli that can cause gel-swelling transitions including solvent composition, pH, and light. Additionally, when two different gel-based valves are arranged in series, the assembly acts as a logical "AND" gate, i.e., water flows through the valve-combination only if it simultaneously satisfies two distinct conditions (such as its pH being below a critical value and its temperature being above a critical value). PMID- 27400461 TI - In the Interest of Clarity. The author responds. PMID- 27400460 TI - Registry Changes Make Life Easier. PMID- 27400462 TI - Medicare Program: Expanding Uses of Medicare Data by Qualified Entities. Final rule. AB - This final rule implements requirements under Section 105 of the Medicare Access and CHIP Reauthorization Act of 2015 that expand how qualified entities may use and disclose data under the qualified entity program to the extent consistent with applicable program requirements and other applicable laws, including information, privacy, security and disclosure laws. This rule also explains how qualified entities may create non-public analyses and provide or sell such analyses to authorized users, as well as how qualified entities may provide or sell combined data, or provide Medicare claims data alone at no cost, to certain authorized users. In addition, this rule implements certain privacy and security requirements, and imposes assessments on qualified entities if the qualified entity or the authorized user violates the terms of a data use agreement required by the qualified entity program. PMID- 27400463 TI - Medication Assisted Treatment for Opioid Use Disorders. Final rule. AB - This final rule increases access to medication-assisted treatment (MAT) with buprenorphine and the combination buprenorphine/naloxone (hereinafter referred to as buprenorphine) in the office-based setting as authorized under the United States Code. Section 303(g)(2) of the Controlled Substances Act (CSA) allows individual practitioners to dispense or prescribe Schedule III, IV, or V controlled substances that have been approved by the Food and Drug Administration (FDA). Section 303(g)(2)(B)(iii) of the CSA allows qualified practitioners who file an initial notification of intent (NOI) to treat a maximum of 30 patients at a time. After 1 year, the practitioner may file a second NOI indicating his/her intent to treat up to 100 patients at a time. This final rule will expand access to MAT by allowing eligible practitioners to request approval to treat up to 275 patients under section 303(g)(2) of the CSA. The final rule also includes requirements to ensure that patients receive the full array of services that comprise evidence-based MAT and minimize the risk that the medications provided for treatment are misused or diverted. PMID- 27400464 TI - Medical Devices; Neurological Devices; Classification of the Thermal System for Insomnia. Final order. AB - The Food and Drug Administration (FDA) is classifying the thermal system for insomnia into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the thermal system for insomnia's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 27400465 TI - Americans' Experiences with ACA Marketplace Coverage: Affordability and Provider Network Satisfaction: Findings from the Commonwealth Fund Affordable Care Act Tracking Survey, February--April 2016. AB - For people with low and moderate incomes, the Affordable Care Act's tax credits have made premium costs roughly comparable to those paid by people with job-based health insurance. For those with higher incomes, the tax credits phase out, meaning that adults in marketplace plans on average have higher premium costs than those in employer plans. The law's cost-sharing reductions are reducing deductibles. Lower-income adults in marketplace plans were less likely than higher-income adults to report having deductibles of $1,000 or more. Majorities of new marketplace enrollees and those who have changed plans since they initially obtained marketplace coverage are satisfied with the doctors participating in their plans. Overall, the majority of marketplace enrollees expressed confidence in their ability to afford care if they were to become seriously ill. This issue brief explores these and other findings from the Commonwealth Fund Affordable Care Act Tracking Survey, February--April 2016. PMID- 27400466 TI - Efficacy and safety of Yinchenwuling powder for hyperlipidemia: a systematic review and Meta-analysis. AB - OBJECTIVE: To assess the clinical effectiveness and adverse effects of Yinchenwuling powder (YCWLP) in the treatment of hyperlipidemia using Meta analysis. METHODS: Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015. Two reviewers independently identified articles, extracted data, assessed quality, and cross checked the results. Revman 5.3 was used to analyze the data. RESULTS: Only five randomized controlled trials with poor methodology were included in the analysis. The five trials compared YCWLP with conventional lipid-lowering drugs. Meta analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides, while increasing the level of high-density lipoprotein cholesterol without serious adverse effects. However, it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology. CONCLUSION: YCWLP appeared to improve lipid levels. However, given the high risk of bias among the trials, we could not conclude that YCWLP was beneficial to patients with hyperlipidemia. More rigorous trials are required to provide stronger evidence for the conclusion. PMID- 27400467 TI - Danshenchuanxiongqin injection in the treatment of unstable angina pectoris: a systematic review and Meta-analysis. AB - OBJECTIVE: To evaluate systematically the efficacy and safety of Danshenchuanxiongqin Injection (DCI) in the treatment of unstable angina pectoris (UAP). METHODS: Randomized controlled trials (RCTs) regarding DCI used for treating UAP were searched in English and Chinese electronic databases from inception to January 2014. Two reviewers independently retrieved RCTs and extracted relevant information. The Cochrane risk of bias method was used to assess the quality of included studies, and a Meta-analysis was conducted with Review Manager 5.2 software. RESULTS: Eleven RCTs involving 1034 participants were included. The methodological quality was relatively passable. The Meta analysis indicated that the combined use of DCI and conventional treatment with Western Medicine (WM) was more efficacious in the outcomes of total effective rate [Relative Risk (RR) = 1.27, 95% CI (confidence interval; 1.18, 1.35), P < 0.000 01], the total effective rate of ECG [RR = 1.40, 95% CI (1.18, 1.66), P < 0.000 01], total cholesterol [Mean difference (MD) = -0.58, 95% CI (- 0.83, - 0.33), P < 0.000 01], total triglycerides [MD = - 0.36, 95% CI (- 0.54, - 0.17), P = 0.0001], and the number of ST-segment depression [MD = -0.36, 95% CI (- 0.54, - 0.17), P = 0.0001]. There were two adverse drug reactions reported in one study. CONCLUSION: Based on the systematic review, DCI combined with WM appeared to be efficacious in the treatment UAP. However, the evidence of DCI for treating UAP requires large-scale and double-blind RCTs to substantiate these findings. PMID- 27400468 TI - Curative effect of acupuncture on quality of life in patient with depression: a clinical randomized single-blind placebo-controlled study. AB - OBJECTIVE: To evaluate the effect of acupuncture on the quality of life in patients with depression by clinical randomized single-blind placebo-controlled study. METHODS: one hundred and sixty-three cases of depression according with the inclusion criteria were randomly divided into a group of acupuncture dredging liver and regulating flow of theosophy (group 1), a group of acupoint shallow stab (group 2) and a group of non-acupoint shallow stab (group 3) at 1 : 1 : 1 ratio, and treated with acupuncture, moxibustion, and intradermal embedding of needle, twice a week, for a total of 12 weeks. Scale of Quality of Life (SF-36) was used to measure the scores at four different time points and evaluate the effect of acupuncture on the quality of life of the patients with depression. RESULTS: At each time point after treatment, in scores of the 8 items, physical function, physical role, bodily pain, general physical condition, energy, social function, emotional function and mental health there were statistically significant differences among the 3 groups (P < 0.0125). CONCLUSION: Acupuncture can effectively improve the quality of life of patients with depression. PMID- 27400469 TI - Evaluation of anti-aphthous activity of decoction of Nicotiana tabacum leaves as a mouthwash: a placebo-controlled clinical study. AB - OBJECTIVE: To determine the effects of decoction derived from the leaves of Nicotiana tabacum (L.) as a mouthwash on minor recurrent aphthous. METHODS: A randomized double-blinded placebo-controlled clinical trial was conducted on 60 patients with minor recurrent aphthous. Treatment comprised of application of tobacco or placebo mouthwash (10 mL 3 times a day) for 5 days. Clinical evaluation included pain level using a visual analog scale and ulcer size on days 1, 3, and 5 were measured. Adverse effects after mouthwash application were recorded, and the oral mucosa was examined by the investigator at each visit. RESULTS: A total of 54 subjects with the mean age (38 +/- 10) years fulfilled the study. No minor and major adverse effects were observed. In the treatment group, ulcer pain score was decreased by 79.2% and 93.8% and ulcer size was reduced by 69.1% and 92.2% (days 3 and 5, respectively), which was significantly greater than the control group (P < 0.01). CONCLUSION: The decoction prepared with of Nicotiana tabacum leaves, used as mouthwash are well-tolerated and safe, and can be used for the management of recurrent aphthous. PMID- 27400470 TI - Reliability and validity of tongue color analysis in the prediction of symptom patterns in terms of East Asian Medicine. AB - OBJECTIVE: To examine whether color parameters of tongue inspection (TI) using a digital camera was reliable and valid, and to examine which color parameters serve as predictors of symptom patterns in terms of East Asian medicine (EAM). METHODS: Two hundred female subjects' tongue substances were photographed by a mega-pixel digital camera. Together with the photographs, the subjects were asked to complete Yin deficiency, Phlegm pattern, and Cold-Heat pattern questionnaires. Using three sets of digital imaging software, each digital image was exposure- and white balance-corrected, and finally L* (luminance), a* (red-green balance), and b* (yellow-blue balance) values of the tongues were calculated. To examine intra- and inter-rater reliabilities and criterion validity of the color analysis method, three raters were asked to calculate color parameters for 20 digital image samples. Finally, four hierarchical regression models were formed. RESULTS: Color parameters showed good or excellent reliability (0.627-0.887 for intra class correlation coefficients) and significant criterion validity (0.523-0.718 for Spearman's correlation). In the hierarchical regression models, age was a significant predictor of Yin deficiency (beta = 0.192), and b* value of the tip of the tongue was a determinant predictor of Yin deficiency, Phlegm, and Heat patterns (beta = - 0.212, - 0.172, and - 0.163). Luminance (L*) was predictive of Yin deficiency (beta = -0.172) and Cold (beta = 0.173) pattern. CONCLUSION: Our results suggest that color analysis of the tongue using the L*a*b* system is reliable and valid, and that color parameters partially serve as symptom pattern predictors in EAM practice. PMID- 27400471 TI - Transcriptome analysis of blood stasis syndrome in subjects with hypertension. AB - OBJECTIVE: To screen for mRNAs associated with blood stasis syndrome and to explore the genetic mechanisms of blood stasis syndrome in hypertension. METHODS: This study involved groups of patients with hypertension and blood stasis, including those with Qi deficiency, Qi stagnation, cold retention and heat retention; as well as hypertensive patients without blood stasis and healthy individuals. Human umbilical vein endothelial cells were co-cultured with the sera of these healthy individuals and patients with blood stasis syndrome. Total RNA was extracted from these cells and assessed by a high-throughput sequencing method (Solexa) and digital gene expression. Differentially expressed genes among these six groups were compared using whole genome sequences, and mRNAs associated with blood stasis syndrome identified. Differences in gene use and gene ontology function were analyzed. Genes enriched significantly and their pathways were determined, as were network interactions, and encoded proteins. Gene identities were confirmed by real-time polymerase chain reactions. RESULTS: Compared with cells cultured in sera of the blood stasis groups, those culture in sera of healthy individuals and of the non-blood stasis group showed 11 and 301 differences, respectively in stasis-related genes. Genes identified as differing between the blood stasis and healthy groups included activating transcription factor 4, activating transcription factor 3, DNA-damage inducible transcription factor 3, Tribbles homolog 3, CCAAT/enhancer binding protein-beta, and Jun proto oncogene (JUN). Pathway and protein interaction network analyses showed that these genes were associated with endoplasmic reticulum stress. Cells cultured in sera of patients with blood stasis and Qi deficiency, Qi stagnation, heat retention, and cold retention were compared with cells cultured in sera of patients with the other types blood stasis syndrome. The comparison showed differences in expression of 28, 28, 34, and 32 specific genes, respectively. CONCLUSION: The pathogenesis of blood stasis syndrome in hypertension is related to endoplasmic reticulum stress and involves the differential expression of the activating transcription factor 4, activating transcription factor 3, DNA-damage inducible transcription factor 3, Tribbles homolog 3, CCAAT/enhancer binding protein-beta, and JUN genes. PMID- 27400472 TI - Combination of ribavirin and reduning protects mice against severe pneumonia induced by H1N1 influenza a virus. AB - OBJECTIVE: To investigate the effects of ribavirin administration combined with Reduning in a mouse model of influenza A (H1N1)-induced severe pneumonia. METHODS: Influenza A/Beijing/501/2009 (H1N1)-infected C57BL/6 mice were randomly divided into four experimental groups treated with either a mock injection of phosphate-buffered saline (PBS), ribavirin (66.6 mg/kg daily) or Reduning (86.6 mg/ kg daily), or a combination of both, for 7 days. Mice were monitored for clinical signs and survival, and body weight was measured daily for 14 days. Virus titer, lung wet-to-dry ratios, pathology and cytokines including interleukin (IL)-6, IL-10, and interferon (IFN)-gamma were assayed on different days. RESULTS: In the untreated group injected with phosphate buffer saline, all the mice died of the infection. The survival rate of mice treated with Reduning was only 10%, whereas 100% of the ribavirin- and the combination-treated mice survived. Low lung viral loads indicated that ribavirin significantly inhibited virus replication, whereas Reduning did not. Lung wet-to-dry ratios demonstrated that both ribavirin and Reduning, administered together or separately, reduced acute lung edema compared with results in the untreated group. Pathology analyses also showed that treatment with a combination of both drugs relieved pathological lesions, whereas the single drug treatment did not. Levels of IL-6, IL-10 and IFN gamma in mice treated with ribavirin or the combination of both ribavirin and Reduning were all significantly lower than in the untreated group, especially in the combination-treated group. In addition, Reduning administration significantly decreased both IL-6 and IL-10 production but had no effect on IFN-gamma. CONCLUSION: Due to the synergistic effect of antiviral and antiinflammation, the combination of ribavirin and Reduning could be an effective treatment for severe H1N1 which was considered to be significant to delayed antiviral and drug resistant. PMID- 27400473 TI - Extrusion process of Acanthopanax senticosus leaves enhances the gastroprotective effect of compound 48/80 on acute gastric mucosal lesion in rats. AB - OBJECTIVE: To investigate the gastroprotective effects of Acanthopanax senticosus leaves (ASLs) extrusion on acute gastric mucosal lesion in rats induced by compound 48/80 (C48/80). METHODS: Rats were divided into six groups: normal; C48/80-induced gastric lesion control; gastric lesion positive control (famotidine 4 mg/kg); gastric lesion administered with two levels of extruded ASLs (ASLE, 40 and 200 mg/kg); and gastric lesion treated with ASLs (ASL 200 mg/kg). Mucus secretion/damage was determined by immunohistological staining. Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression. Gastric mucosal oxidative-stress-related enzymes and malondialdehvde were determined. RESULTS: C48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs. The increased serum serotonin and histamine concentrations in C48/80 treated rats were also attenuated by ASLs. Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment, and ASLs ameliorated Bax and Bcl-2 expression. The extrusion process significantly augmented the effects of ASLs in a dose-dependent manner. ASLEs at 200 mg/kg normalized mucus damage/secretion, C48/80-induced increases of mucosal myeloperoxidase activity (index of inflammation), xanthine oxidase, and malondialdehyde content (index of lipid peroxidation). The effects of ASLs on Bax and Bcl-2 expression were also enhanced by extrusion. Furthermore, these effects of ASLEs at 200 mg/kg were similar to those of famotidine, a histamine H2 receptor antagonist commonly used to treat gastric ulcers. CONCLUSION: ASLEs prevented acute gastric mucosal lesion progression induced by C48/80, possibly by inducing mucus production, and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism. PMID- 27400474 TI - Effect of Pingan Fang, a Traditional Chinese Medicine compound, on behavioral sensitization and conditioned place preference induced by ethanol in mice. AB - OBJECTIVE: To observe the effect of Pingan Fang (PG) on behavioral sensitization and conditioned place preference (CPP) induced by ethanol in mice, and to determine the intervention mechanism of PG on alcohol addiction. METHODS: A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice. The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol. Concentrations of dopamine (DA), Glutamate (Glu), and a-aminobutyric acid (GABA) in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay. RESULTS: Although PG did not alter spontaneous activity in mice, it reduced the growth of spontaneous activity stimulated by ethanol. The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased. CONCLUSION: Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system. This suggests that PG might be useful for the prevention and treatment of alcohol addiction. PMID- 27400475 TI - Uric acid lowering effect of Tibetan Medicine RuPeng15 powder in animal models of hyperuricemia. AB - OBJECTIVE: To evaluate the influence of the Tibetan medicine RuPeng15 powder (RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models. METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily (30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase (XOD) was assayed using a commercial test kit. RESULTS: RPP15 (0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats (P < 0.05). Furthermore, hyperuricemic rats treated with RPP15 (0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels (P < 0.05), accompanied by lower urine uric acid (P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly (P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15 (P < 0.05). CONCLUSION: RPP15 (0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD. PMID- 27400476 TI - Puerarin affects bone biomarkers in the serum of rats with intrauterine growth restriction. AB - OBJECTIVE: To investigate serum bone biomarkers in rats with intrauterine growth restriction (IUGR) in order to determine the effects of puerarin on bone metabolism. METHODS: A rat model of IUGR was induced using a low protein diet during pregnancy. The offspring were given puerarin or an identical volume of saline via subcutaneous abdominal injection. All rats were studied at 1, 3, and 8 weeks of age. Serum biomarkers of bone formation, including insulin-like growth factor-1 (IGF-1), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), osteoprotegerin (OPG), receptor-activator of nuclear factor-kappaB Iigand (RANKL), as well as blood levels of calcium and phosphorus were measured. RESULTS: Serum BALP, OPG, IGF-1, and OC levels, as well as the OPG/RANKL ratio, were lower in the IUGR group compared with the control group at 1 week of age (P = 0.024, 0.011, 0.014, 0.004, and 0.002, respectively). At 3 weeks of age, the serum BALP and OC levels were higher in the protein-restricted group compared with the control group (P = 0.003 and 0.001, respectively). A comparison between the IUGR plus puerarin intervention group and the IUGR group revealed differences in the levels of BALP and IGF-1 at 3 weeks of age (P = 0.008 and 0.003, respectively). In addition, serum OPG and OC levels and the OPG/RANKL ratio were higher at 8 weeks of age (P = 0.044, 0.007, and 0.016, respectively). No differences in serum calcium and phosphorus levels were observed among the three groups. CONCLUSION: Our study demonstrates that the bone microenvironment of the fetus can be altered by a low protein maternal diet and that puerarin can reverse these effects. These results indicate that the nutritional environment plays an important role in early skeletal development and that the bone turnover of IUGR rats can be altered by puerarin treatment. PMID- 27400477 TI - Panax notoginseng saponins ameliorates experimental hepatic fibrosis and hepatic stellate cell proliferation by inhibiting the Jak2/ Stat3 pathways. AB - OBJECTIVE: To investigate the inhibitory effect of Panax notoginseng saponins (PNS) on liver fibrosis and explore the underlying mechanisms. METHODS: Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. The effect of PNS on CCl4-induced liver fibrosis was studied with histochemical and biochemical analysis. Transforming growth factor (TGF)-beta1, alpha-smooth muscle actin (alpha-SMA), and collagen I mRNA expression were determined by reverse transcripwhile, the protein expression levels of alpha-SMA, collagen I, phosphorylation-Janus activated kinase signal transducer (p-Jak2)/Jak2, and phosphorylation-activator of transcription (p-Stat)3/Stat3 were determined by immunohistochemistry and/or immunoblotting. RESULTS: PNS treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase and aspartate aminotransferase. Histopathological results indicated that PNS alleviated liver damage and reduced the formation of fibrous septa. Moreover, PNS significantly decreased liver hydroxyproline and significantly attenuated expressions of collagen I, alpha-SMA, TGF-beta1, p-Jak2 / Jak2, and p-Stat3/Stat3 in the rat liver fibrosis model and HSCs. CONCLUSION: PNS can relieve liver fibrosis by modulating Jak2/Stat3 signaling transduction pathway, which may be one of its mechanisms to suppress hepatic fibrosis. PMID- 27400479 TI - Use of microbial fuel cells to monitor current production in Qi-deficient liver cells. AB - OBJECTIVE: To monitor current production in Qi-deficient liver cells, and to study how cellular proton leakage might affect electric current production. METHODS: Cells were placed in an microbial fuel cells (MFC) anode and the electric current was measured. Mitochondrial-affecting chemicals, 2,4 dinitrophenol (DNP) and resveratrol (RVT), were used to induce proton leakage in cells and their effect on current production observed. MCF-7 breast cancer cells exhibited higher proton leakage relative to normal liver cells. A mouse model for Qi-deficiency was prepared according to the Methodology of Animal Experiment in Chinese medicine. The Qi-tonics Buzhongyiqi Tang (BZYQT), which is used to treat the Qi-deficiency condition, was applied to Qi-deficient liver cells to examine how current production was altered. RESULTS: Adding either DNP or RVT to normal liver cells increased current production. MCF-7 cells that possessed high proton leakage were also found to produce higher currents than normal liver cells. Higher current production, lower cellular glucose content, and lower adenosine triphosphate (ATP) production rate were found in Qi-deficient liver cells, in which the use of DNP or RVT further increased current production. The use of BZYQT to treat Qi-deficient liver cells decreased current production, counteracted the action of DNP, and also improved cellular glucose content. CONCLUSION: High electric current production was found in liver cells with high cellular proton leakage. Positive current responses to both mitochondria affecting chemicals, DNP and RVT, appeared to indicate proper mitochondrial function. The high proton leakage detected in Qi-deficient liver cells might have caused high energy losses, which served to explain the observed lower cellular glucose content and ATP production rate than in normal cells. These results might also explain the exhibited syndromes of low energy and fatigue in Qi-deficient patients. Proton leakage, induced by DNP or the Qi-deficient condition, was possibly caused by unusual uncoupling of oxidative phosphorylation and appeared to be inhibited by treatment with BZYOT such that decreased current production was observed after BZYQT treatment. PMID- 27400478 TI - Inhibitory effect of oridonin on proliferation of RPMI8226 cells and the possible underlying mechanism. AB - OBJECTIVE: To observe the effects of oridonin on proliferation and apoptosis of myeloma RPMI8226 cells and to investigate the potential underlying mechanisms. METHODS: RPMI8226 cells were treated with various concentrations of oridonin. Cell proliferation was analyzed using the thiazolyl blue tetrazolium bromide method. Ultramicrostructure was observed by transmission electron microscopy. Annexin-V/PI staining and flow cytometry was performed to determine cell apoptosis. Expression of apoptosis-related proteins was evaluated by western blot analysis. RESULTS: Oridonin suppressed the proliferation of RPMI8226 cells and induced apoptosis in a time-and dose-dependent manner. Transmission electron microscopy confirmed apoptotic morphology upon treatment with 20 MUmol/L oridonin and western blot revealed decreased expressions of the apoptosis suppressors survivin, Bcl-2 and pro-caspase-3 proteins, and the increased expression of the apoptosis inducer Bax. CONCLUSION: Our results show that oridonin exhibits an inhibitory effect on the proliferation of RPMI8226 cells and induces apoptosis. This is associated with altering the balance between Bcl-2 and Bax protein expressions and decreased survivin and pro-caspase-3 expressions. PMID- 27400480 TI - Correlation between the transdermal characteristics of pseudoephedrine and amygdalin in majiepingchuan in vitro. AB - OBJECTIVE: To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction. METHODS: A Franz diffusion cell was used in vitro to evaluate the transdermal parameters of cumulative transdermal flux (Q(tot)), cumulative transmission (T(tot)), and mean penetration rate (Kp) of pseudoephedrine and amygdalin in majiepingchuan. Linear regression analyses of Q(tot) over time of pseudoephedrine vs amygdalin and their ratios was adopted for correlation evaluation. RESULTS: At 1, 2, 4, 6, and 8 h, the Q(tot), T(tot) and Kp of pseudoephedrine showed a good correlation with that of amygdalin. CONCLUSION: There was a small difference in the ratios of Q(tot), T(tot) and Kp between pseudoephedrine and amygdalin, and a correlation between them. PMID- 27400481 TI - Therapeutic targets of Traditional Chinese Medicine for colorectal cancer. AB - OBJECTIVE: To explore the role of Traditional Chinese Medicine (TCM) in the prevention and treatment of colorectal cancer and identify possible therapeutic targets of TCM to provide clues for the use of TCM for colorectal cancer prevention and treatment in the clinic and to find novel directions for new drug discovery for colorectal cancer. METHODS: We used PubMed and Google to search for and collect scientific publications for a full evalu- ation of current evidence in the literature indicating the potential role of Chinese herbal medicines and their respective ingredients as effective candidates for colorectal cancer prevention and treatment. RESULTS: We extracted a detailed description of potential therapeutic Chinese herbal medicines and their constituent ingredients that target different mechanisms in colorectal cancer such as gene mutation, dysregulation of signaling pathways, metabolism disorders, and the inflammatory microenvironment, including both conventional and non-conventional approaches. CONCLUSION: TCM may be a promising complementary and alternative therapy for the treatment of colorectal cancer. PMID- 27400482 TI - Potential therapeutic applications for Terminalia chebula in Iranian traditional medicine. AB - Terminalia chebula (family: Combretaceae) is widely used in the traditional medicine of India and Iran to treat diseases that include dementia, constipation, and diabetes. This tree is known in Iranian traditional medicine (ITM) as halileh or halilaj and the fruit is used to develop treatments. It is described in ITM as an astringent that has a "cold" and "dry" temperament. References to the medicinal properties of Terminalia chebula were collected from important ITM sources and from modern medical databases (PubMed, Scirus, ScienceDirect, and Scopus). The medicinal properties described for this tree in ITM were compared with those reported in studies of modern phytotherapy. The results confirm that the tree referred to as halileh in traditional books is the Terminalia chebula used in present-day studies. Treatments that have not been evaluated in modern phytotherapy but have been traditionally treated with Terminalia chebula include fever, and psychological and psychiatric issues. This article confirms the medicinal uses of Terminalia chebula. PMID- 27400484 TI - Once upon a time. PMID- 27400483 TI - Analysis of factors influencing moxibustion efficacy by affecting heat-activated transient receptor potential vanilloid channels. AB - Moxibustion is an important component part of Traditional Chinese Medicine (TCM). Among differ- ent kinds of moxibustion methods, thermal stimulation seems to be a pivotal impact factor to the theraputic efficacy. Based on its thermal characteristic and treated area-skin, we hypothesize that the thermosensitive TRPV channels may involve in the mechanism of moxibustion. This study, by referring to various experimental and clinical data, analyzes the properties and features of transient receptor potential vanilloid (TRPV) subfamily 1-4 and the impact of moxibustion on these channels. The factors impacting the efficacy of moxibustion treatment were analyzed on three levels: the independent basic factors of moxibustion (temperature, space and time); moxibustion intensity (a compound factor achieved through comprehensive control of the three individual basic factors mentioned above); and moxibustion quantity (the amount of temperature stimulation applied within a certain unit of time, including the total amount of moxibustion treatment). The results from present study show that the effect of moxibustion therapy appears to be determined by the activation of TRPV1-4, mainly TRPV1 and TRPV2. Temperature (the degree of heat stimulation), time and area (how long the treatment lasts and how many TRPV1-4 channels are activated) affect the intensity of moxibustion treatment to form effective moxibustion quantity; this should be considered in clinical moxibustion application. PMID- 27400485 TI - News Update Unique Trust and University partnership prepares nursing graduates the Northumbria way. PMID- 27400486 TI - Perioperative care. the foundations of quality practice for the child and young person. PMID- 27400487 TI - Auditing the needs of recovery room staff providing care for the child in an acute hospital. AB - This article examines the results of an audit into recovery nurse knowledge and understanding of paediatric care standards. It will critically analyse the availability of current standards for children's services in the recovery room and discuss the need for a national document specifically dedicated to standards of practise for the care of the child in the recovery room providing immediate post operative care. The article will also look at the development of such a document. PMID- 27400488 TI - Increasing operating room efficiency through electronic medical record analysis. AB - We used electronic medical record (EMR) analysis to determine errors in operating room (OR) time utilisation. Over a two year period EMR data of 44,503 surgical procedures was analysed for OR duration, on-time, first case, and add-on time performance, within 19 surgical specialties. Maximal OR time utilisation at our institution could have saved over 302,620 min or 5,044 hours of OR efficiency over a two year period. Most specialties (78.95%) had inaccurately scheduled procedure times and therefore used the OR more than their scheduled allotment time. Significant differences occurred between the mean scheduled surgical durations (101.38 +/- 87.11 min) and actual durations (108.18 +/- 102.27 min; P < 0.001). Significant differences also occurred between the mean scheduled add-on durations (111.4 +/- 75.5 min) and the actual add-on scheduled durations (118.6 +/- 90.1 minutes; P < 0.001). EMR quality improvement analysis can be used to determine scheduling error and bias, in order to improve efficiency and increase OR time utilisation. PMID- 27400489 TI - Just a routine operation: a critical discussion. AB - This article has summarised a critical discussion of the human factors that contributed to the death of a patient from a failure to respond appropriately to a 'can't intubate, can't ventilate' scenario. The contributory factors included the clinical team's inability to communicate, prioritise tasks and demonstrate effective leadership and assertive followership. The film Just a routine operation has now been in circulation for several years. When a system is designed and introduced with the intention of making a change to clinical practice, it can quickly become just another component of an organisation's architecture and complacency around its use can develop. This article has been written specifically for perioperative practitioners to renew the debate around the human factors that contribute to patient harm. By critically discussing Just a routine operation and attempting to review why the incident occurred, this article has attempted to emphasise that some of the conditions and behaviours that contributed to the death of Elaine Bromiley may be latent within our organisations and teams, and may continue to contribute to failures that affect patient safety. PMID- 27400490 TI - Regional uptake an variations in orthopaedic enhanced recovery pathways in knee and hip total arthroplasty. AB - The use of enhanced recovery (ER) pathways for hip and knee arthroplasty has increased over the last decade, and the adoption within orthopaedics is becoming more common. We have demonstrated a regional variation and institutional inconsistency of uptake and delivery of ER pathways in our region. Units that have a unified pathway were more likely to have consistency in treatment and early analgesia for patients. We would advocate that units use an agreed enhanced recovery pathway to optimise patient recovery from hip and knee arthroplasties. PMID- 27400491 TI - Ruptured ectopic pregnancy. PMID- 27400492 TI - [Radiation Environment Study of Near Space in China Area]. AB - Aerospace activity in near space (20-50 km) has become a research hotspot for aviation big countries worldwide. Solar radiation study, as the prerequisite to carry out aerospace activity, is facing the barrier of lacking of observation in near space layer. Ozone is the most important factor that affects radiation value in this layer. Based on ECMWF reanalysis data, this input key parameter and its horizontal, vertical and temporal characteristics are analyzedwith results showing obvious regional features in temporal-spatial distribution and varieties. With meteorological data and surface parameters, near space over China is divided into 5 parts. Key factors' value is confirmed over each division. With SBDART radiation transfer model, solar radiation and ultraviolet radiation simulation in near space are conducted separately. Results show that it is influenced by latitude, total ozone and its vertical distribution, radiation varies under complex rules. The average year and monthly solar radiation strengthens changes with latitude reduction, while annual range changes reversely. Air absorbing is related to latitude and land-sea contrast and shows different values and seasonal variations. The ultraviolet radiation over South China Sea reaches its maximum value and minimum annual range, as well as minimum monthly range with value strengthening in summer and weakening in winter. In other areas radiation increases in summer while weakens in winter, monthly range shows double peaks with higher value in spring and autumn, lower in summer and winter. Air absorption in ultraviolet radiation is influenced by multiple factors, vertical varieties over areas besides South China Sea enhance in summer time. The vertical changes of monthly ranges affected by air absorption show consistence in higher and lower layer in June and July, while in other months ranges are bigger in higher layer. PMID- 27400493 TI - [Correction Method of Atmospheric Scattering Effect Based on Three Spectrum Bands]. AB - As a major error of CO2 retrieval, atmospheric scattering effect hampers the application of satellite products. Effect of aerosol and combined effect of aerosol and ground surface are important source of atmospheric scattering, so it needs comprehensive consideration of scattering effect from aerosol and ground surface. Based on the continuum, strong and weak absorption part of three spectrum bands O2-A, CO2 1.6 MUm and 2.06 MUm, information of aerosol and albedo was analyzed, and improved full physics retrieval method was proposed, which can retrieve aerosol and albedo simultaneously to correct the scattering effect. Simulation study on CO2 error caused by aerosol and ground surface albedo CO2 error by correction method was carried out. CO2 error caused by aerosol optical depth and ground surface albedo can reach up to 8%, and CO2 error caused by different types of aerosol can reach up to 10%, while these two types of error can be controlled within 1% and 2% separately by this correction method, which shows that the method can correct the scattering effect effectively. Through evaluation of the results, the potential of this method for high precision satellite data retrieval is obvious, meanwhile, some problems which need to be noticed in real application were also pointed out. PMID- 27400494 TI - [The Diagnostics of Detonation Flow External Field Based on Multispectral Absorption Spectroscopy Technology]. AB - Compared with traditional sampling-based sensing method, absorption spectroscopy technology is well suitable for detonation flow diagnostics, since it can provide with us fast response, nonintrusive, sensitive solution for situ measurements of multiple flow-field parameters. The temperature and concentration test results are the average values along the laser path with traditional absorption spectroscopy technology, while the boundary of detonation flow external field is unknown and it changes all the time during the detonation engine works, traditional absorption spectroscopy technology is no longer suitable for detonation diagnostics. The trend of line strength with temperature varies with different absorption lines. By increasing the number of absorption lines in the test path, more information of the non-uniform flow field can be obtained. In this paper, based on multispectral absorption technology, the reconstructed model of detonation flow external field distribution was established according to the simulation results of space-time conservation element and solution element method, and a diagnostic method of detonation flow external field was given. The model deviation and calculation error of the least squares method adopted were studied by simulation, and the maximum concentration and temperature calculation error was 20.1% and 3.2%, respectively. Four absorption lines of H2O were chosen and detonation flow was scanned at the same time. The detonation external flow testing system was set up for the valveless gas-liquid continuous pulse detonation engine with the diameter of 80 mm. Through scanning H2O absorption lines with a high frequency of 10 kHz, the on-line detection of detonation external flow was realized by direct absorption method combined with time division multiplexing technology, and the reconstruction of dynamic temperature distribution was realized as well for the first time, both verifying the feasibility of the test method. The test results show that both of the temperature and H2O concentration rose with the arrival of detonation wave. With the increase of the vertical distance between the detonation tube nozzle and the laser path, the time of temperature and concentration coming to the peak delayed, and the temperature variation trend tended to slow down. At 20 cm from detonation tube nozzle, the maximum temperature hit 1 329 K and the maximum H2O concentration of 0.19 occurred at 4 ms after ignition. The research can provide with us the support for expanding the detonation test field with absorption spectroscopy technology, and can also help to promote the detonation mechanism research and to enhance the level of detonation engine control technology. PMID- 27400495 TI - [A Method to Measure the Velocity of Fragments of Large Equivalence Explosion Field Based on Explosion Flame Spectral Analysis]. AB - The deflagration fire lasting for a long time and covering a large area in the process of large equivalent explosion makes it difficult to obtain velocity parameters of fragments in the near-field. In order to solve the problem, it is proposed in this paper a photoelectric transceiver integrated method which utilize laser screen as the sensing area. The analysis of three different types of warhead explosion flame spectral distribution of radiation shows that 0.3 to 1.0 MUm within the band is at relatively low intensity. On the basis of this, the optical system applies the principle of determining the fixed distance by measuring the time and the reflector technology, which consists of single longitudinal mode laser, cylindrical Fresnel lens, narrow-band filters and high speed optical sensors, etc. The system has its advantage, such as transceiver, compact structure and combination of narrowband filter and single longitudinal mode laser, which can stop the spectrum of fire from suppressing the interference of background light effectively. Large amounts of experiments in different models and equivalent have been conducted to measure the velocity of difference kinds of warheads, obtaining higher signal-to-noise ratio of the waveform signal after a series of signal de-noising and recognition through NI company data acquisition and recording system. The experimental results show that this method can complete the accurately test velocity of fragments around center of the explosion. Specifically, the minimum size of fragments can be measured is 4 mm while the speed can be obtained is up to 1 200 m x s(-1) and the capture rate is better than 95% comparing with test results of target plate. At the same time, the system adopts Fresnel lenses-transparent to form a rectangular screen, which makes the distribution of rectangular light uniform in vertical direction, and the light intensity uniformity in horizontal direction is more than 80%. Consequently, the system can distinguish preliminarily the correspondence between the velocity and the sizes of prefabricated fragments. PMID- 27400496 TI - [Study on the Properties of the Pc-Si Films Prepared by Magnetron Co-Sputtering at Low Temperature]. AB - The polycrystalline silicon thin films play an important role in the field of electronics. In the paper, alpha-SiAl composite membranes on glass substrates was prepared by magnetron co-sputtering. The contents of Al radicals encapsulated-in the alpha-Si film can be adjusted by changing the Al to Si sputtering power ratios. The as-prepared alpha-Si films were converted into polycrystalline films by using a rapid thermal annealing (RTP) at low temperature of 350 degrees C for 10 minutes in N2 atmosphere. An X-ray diffractometer, and Raman scattering and UV Visible-NIR Spectrometers were used to characterize the properties of the Pc-Si films. The influences of Al content on the properties of the Pc-Si films were studied. The results showed that the polycrystalline silicon films were obtained from alpha-SiAl composite films which were prepared by magnetron co-sputtering at a low temperature following by a rapid thermal annealing. The grain size and the degree of crystallization of the Pc-Si films increased with the increase of Al content, while the optical band gap was reduced. The nc-Si films were prepared when the Al to Si sputtering power ratio was 0.1. And a higher Crystallization rate (>= 85%) of polycrystalline silicon films were obtained when the ratio was 0.3. The band gaps of the polycrystalline silicon films can be controlled by changing the aluminum content in the films. PMID- 27400497 TI - [Polarization Modeling and Analysis of Light Scattering Properties of Multilayer Films on Slightly Rough Substrate]. AB - To satisfy the demand of multilayer films on polarization detection, polarized bidirectional reflectance distribution function of multilayer films on slightly rough substrate is established on the basis of first-order vector perturbation theory and polarization transfer matrix. Due to the function, light scattering polarization properties are studied under multi-factor impacts of two typical targets-monolayer anti-reflection film and multilayer high-reflection films. The result shows that for monolayer anti-reflection film, observing positions have a great influence on the degree of polarization, for the left of the peak increased and right decreased compared with the substrate target. Film target and bare substrate can be distinguished by the degree of polarization in different observation angles. For multilayer high-reflection films, the degree of polarization is significantly associated with the number and optical thickness of layers at different wavelengths of incident light and scattering angles. With the increase of the layer number, the degree of polarization near the mirror reflection area decreases. It reveals that the calculated results coincide with the experimental data, which validates the correctness and rationality of the model. This paper provides a theoretical method for polarization detection of multilayer films target and reflection stealth technology. PMID- 27400498 TI - [Influence of MnO3 on Photoelectric Performance in Organic Light Emitting Diodes]. AB - Organic Light Emitting Diodes (OLEDs) has been a promising new research point that has received much attention recently. Emission in a conventional OLED originates from the recombination of carriers (electrons and holes) that are injected from external electrodes. In the device, Electrons, on the other hand, are injected from the Al cathode to an electron-transporting layer and travel to the same emissive zone. Holes are injected from the transparent ITO anode to a hole-transporting layer and holes reach an emitting zone through the holetransporting layer. Electrons and holes recombine at the emissive film to formsinglet excited states, followed by emissive light. It is because OLED is basically an optical device and its structure consists of organic or inorganic layers of sub-wavelength thickness with different refractive indices. When the electron and holes are injected through the electrodes, they combine in the emission zone emitting the photons. These photons will have the reflection and transmission at each interface and the interference will determine the intensity profile. The emissive light reflected at the interfaces or the metallic electrode returns to the emissive layer and affects the radiation current efficiency. Microcavity OLED can produce saturated colors and narrow the emission spetrum as a new kind of technique. In the paper, we fabricate microcavity OLED using glass substrate. Ag film acts as the anode reflector mirror; NPB serves as the hole transporting material; Alq3 is electron-transporting material and organic emissive material; Ag film acts as cathode reflector mirror. The microcavity OLED structures named as A, B, C and D are glass/Ag(15 nm)/MoO3 (x nm)/NPB(50 nm)/Alq3 (60 nm)/A1(100 nm). Here, A, x = 4 nm; B, x = 7 nm; C, x = 10 nm; D, x = 13 nm. The characteristic voltage, brightness and current of these devices are investigated in the electric field. The luminance from the Devices A, B, C and D reaches the luminance of 928, 1 369, 2 550 and 2 035 cd x m(-2), respectively at 13 V. At 60 mA x cm(-2), the current efficiency of the microcavity OLEDs using MnO3 are about 2.2, 2.6, 3.1 and 2.6 cd x A(-2) respectively. It is found that electrons are majority carriers and holes are minority carriers in this microcavity OLEDs. MnO3 film can improve hole injection ability from 4 to 10 nm. In addition, hole injection ability is increased with the increasing thickness of the MnO3 film. PMID- 27400499 TI - [Temperature-Dependent Photoluminescence Property Studies of SiN(x) Films with nc Si]. AB - Silicon nitride (SiN(x)) films containing nanocrystalline silicon (nc-Si) were deposited on crystalline silicon substrate by facing-target sputtering technique. Thermal annealing process was performed at 450 degrees C for 50 min in a conventional furnace under FG(10% H2, 90% N2) ambient. The photoluminescece (PL) properties of the SiN(x) films with nc-Si were investigated by steady/transient PL spectra measurements by Fluorescence spectrometer with different temperatures. The PL processes could be attributed to the quantum confinement effect of nc-Si and the defects in the film. The PL peak position exhibits a small blue shift with the increasing of the excitation energy, which indicates that the PL portion of the nc-Si increased with smaller size. In addition, the PL lifetime increases and the PL intensity exhibits exponential increase as a result of the decreased temperature which supressed the nonradiative recombination process and then improved the radiative recombination. The PL lifetime of the film significantly reduces with the decreasing of the detection wavelength, which indicates that the PL process related to the the quantum confinement effect strongly depends on temperature. PMID- 27400500 TI - [Study on the Preparation of Ba3Si6O9N4 : Eu(2+) Phosphor and the Characterization of Their Luminescence Properties]. AB - Ba3Si6O9N4 : Eu(2+) phosphors were synthesized by two-step synthesis processes based on high temperature solid phase using BaSiO3 as a precursor. The influence mechanism of the Eu(2+) doping concentration to the luminescence properties of Ba3Si6O9N4 : Eu(2+) phosphors were mainly investigated. This paper made a comparison between the luminescence properties of Ba3Si6ON4 : Eu(2+) phosphors prepared by two-step processes and solid- state reaction method. The results showed that the Ba3Si6O9N4 : Eu(3+) phosphors synthesized by two-step processes had higher purity and higher crystallinity. There exists concentration quenching in Ba3Si6O9N4 : Eu(2+) phosphors for both two-step processes and solid-state reaction when the doping concentration x is more than 9%. Both the concentration quenching mechanism of Ba3 Si 09 N4 : EuI+ phosphor prepared by solid-state reaction and two-step processes is electric dipole-dipole interaction. The emission peak of Ba3Si6O9N4 : Eu(2+) phosphors (peak 489 nm) prepared by two-step processes had a blue shift compared to the emission peak of Ba3Si6O9N4 : Eu2+ phosphors (peak 512nm) prepared by solid-state reaction. The emission peak of Ba3Si6O9N4 : Eu2+ phosphors prepared by two-step processes relatively close to the theoretical value (480 nm). The spectrum analysis result showed that the element component of Ba3Si6O3N4 : Eu2+ phosphors prepared by two-step processes was closer to the theoretical value, it means that the two-step processes can effectively reduce the lattice defects. The Ba3Si6O9N4 : Eu(2+) phosphors synthesized by two-step processes had better thermal stability, which demonstrates to be a highly promising phosphor for white-LED applications. PMID- 27400501 TI - [Study on Indicator Densitometry Determination Method of Hemodynamic Parameters]. AB - Measurement for hemodynamic parameters has always been a hot spot of clinical research. Methods for measuring hemodynamic parameters clinically have the problems of invasiveness, complex operation and being unfit for repeated measurement. To solve the problems, an indicator densitometry analysis method is presented based on near-infrared spectroscopy (NIRS) and indicator dilution theory, which realizes the hemodynamic parameters measured noninvasively. While the indocyanine green (ICG) was injected into human body, circulation carried the indicator mixing and diluting with the bloodstream. Then the near-nfrared probe was used to emit near-infrared light at 735, 805 and 940 nm wavelengths through the sufferer's fingertip and synchronously capture the transmission light containing the information of arterial pulse wave. By uploading the measured data, the computer would calculate the ICG concentration, establish continuous concentration curve and compute some intermediate variables such as the mean transmission time (MTT) and the initial blood ICG concentration (c(t0)). Accordingly Cardiac Output (CO) and Circulating Blood Volume (CBV) could be calculated. Compared with the clinical "gold standard" methods of thermodilution and I-131 isotope-labelling method to measure the two parameters by clinical controlled trials, ten sets of data were obtained. The maximum relative errors of this method were 8.88% and 4.28% respectively, and both of the average relative errors were below 5%. The result indicates that this method can meet the clinical accuracy requirement and can be used as a noninvasive, repeatable and applied solution for clinical hemodynamnic parameters measurement. PMID- 27400502 TI - [Study on Different Parts of Wild and Cultivated Gentiana Rigescens with Fourier Transform Infrared Spectroscopy]. AB - The application of traditional Chinese medicine (TCM) and their preparations have a long history. With the deepening of the research, the market demand is increasing. However, wild resources are so limited that it can not meet the needs of the market. The development of wild and cultivated samples and research on accumulation dynamics of chemical component are of great significance. In order to compare composition difference of different parts (root, stem, and leaf) of wild and cultivated G. rigescens, Fourier infrared spectroscopy (FTIR) and second derivative spectra were used to analyze and evaluate. The second derivative spectra of 60 samples and the rate of affinity (the match values) were measured automatically using the appropriate software (Omnic 8.0). The results showed that the various parts of wild and cultivated G. rigescens. were high similar the peaks at 1732, 1 643, 1 613, 1 510, 1 417, 1 366, 1 322, 1 070 cm(-1) were the characteristic peak of esters, terpenoids and saccharides, respectively. Moreover, the shape and peak intensity were more distinct in the second derivative spectrum of samples. In the second derivative spectrum range of 1 800 600 cm(-1), the fingerprint characteristic peak of samples and gentiopicroside standards were 1 679, 1 613, 1 466, 1 272, 1 204, 1 103, 1 074, 985, 935 cm(-1). The characteristic peak intensity of gentiopicroside of roots of wild and cultivated samples at 1 613 cm(-1) (C-C) was higher than stems and leaves which indicated the higher content of gentiopicroside in root than in stem and leaves. Stems of wild samples at 1 521, 1 462 and 1 452 cm(-1) are the skeletal vibration peak of benzene ring of lignin, and the stem of cultivated sample have stronger peak than other samples which showed that rich lignin in stems. The iInfrared spectrum of samples were similar with the average spectral of root of wild samples, and significant difference was found for the correlation between second derivative spectrum of samples and average spectral of wild samples root, and the sequence of similarity was root > stem > leaf. Therefore, FTIR combined with second derivative spectra was an express and comprehensive approach to analyze and evaluate in the imperceptible differences among different parts of wild and cultivated of G. rigescens. PMID- 27400503 TI - [Rapid FTIR-ATR Method for the Quantification of Bitumen Property]. AB - The quality of bitumen directly affects road performance and road life. Traditional analytical methods-for wax content, softening point and penetration of bitumen are tedious and time-consuming. A new fast method, with which the three properties can be determined at same time, is proposed in this paper. The spectra of 220 bitumen were collected and their wax content, softening point and penetration data were determined according to the standard JTJ052-2000. The quantitative calibration models for wax content, softening point and penetration were established using partial least squares (PLS), with SECV 0.13, 0.88, 3.18 and SEP 0.14, 1.06, 3.90, less than the reproducibility error stipulated in the standard method. Three samples were in random selected to test the repeatability, the results met the precision requirement of the standard method. With its advantages of better repeatability, fast, easy operation, the new method can be used as an alternative for the determination of wax content, softening point and penetration of bitumen. PMID- 27400504 TI - [FTIR Spectroscopic Characterization of Material Composition in Functional Leaf of Cotton under Stress of Potassium and Boron]. AB - Potassium (K) and boron (B) are essential nutrient elements for plants, and the elements play an important role for plant growth, development and physiological metabolism. Cotton has a higher demand for K and B; K deficiency or B deficiency often occurs in cotton though. To reveal the component changes in functional leaf of cotton under K and B stress and investigate effects on material composition from K and B. A pot experiment was conducted at Huazhong Agricultural University. (1) the characteristic peaks at 1 546.86, 1 438.85, 1 153.39 and 1 024.17 cm(-1) disappeared due to B deficiency, and relative absorbance of other characteristic peaks was decreased compared with normal, which suggested that the structures of protein, fiber, soluble sugar and ribosome in cotton functional leaf changed and decreased in cotent when lack of K. (2) the relative absorbance of all characteristic peaks was increased in the B-deficient cotton leaves compared with normal, suggesting B deficiency leads to the accumulation in leaves of protein, and fiber, soluble sugar and other carbohydrates because of the hindered transportation. (3) lack of both potassium and boron, induced significant changes to both the locations and relative absorbance of characteristic peaks, and the content of protein, and soluble sugar and other carbohydrates increased, while the content of nucleic acids and polysaccharides dropped. K deficiency led to the structures of protein, fiber, soluble sugar and ribosome in cotton functional leaf changed and decreased in content; B deficiency gave rise to the accumulation in leaves of protein, and fiber, soluble sugar and other carbohydrates; the content of protein and soluble sugar and other carbohydrates increased, while the content of nucleic acids and polysaccharides dropped when K and B were all in short supply. PMID- 27400505 TI - [Terahertz and Infrared Spectroscopic Investigation of Cellulose]. AB - To investigate the Terahertz's application prospect, corn, wheat husk and reed were used to detect their Terahertz Time Domain Spectroscopy, and be compared with that of cellulose powder. The experimental results show that all of their absorption peaks exist at 1.75, 1.62, 1.1, and 0.7 THz. Absorption intensity of cellulose powder, corn, wheat husk and reed were compared in some frequencies points. It finds that corn, wheat husk and reed have higher absorption intensity than cellulose powder in early frequency domain. However, absorption intensity of cellulose powder is the strongest at 1.62 THz. Cellulose content in corn, wheat husk and reed were detected by using the method of chemical analysis. The peaks of absorption coefficient are related to their cellulose content at this frequency. It shows that plant cellulose occur lattice vibration in the frequency. Deformation, bending, flexing, and other changes appear to their functional keys. Quantum chemical calculation was carried out by using density functional theory to cellulose and the structure diagram of cellulose molecular formula was obtained. It also finds some absorption peaks exist at 0.7, 1.1, and 1.75 THz. Characterization of cellulose clusters mainly includes CH2, OH, CH, and so on. Glucose hydroxyl radical on the ring is active in the cellulose chain. Where hydroxyl related chemical reaction can occur, Hydroxyl can also be integrated into the intermolecular and intramolecular hydrogen bond. Terahertz wave can promote hydrogen bond vibration. This kind of vibration is weak in the intermolecular interaction. The vibration and rotating happen in dipole transition. The crystal lattice rotates and is absorptive in low frequency, and large molecular skeleton vibrates. All of them can show different intensity and position of the absorption peak in the terahertz band. Corn and cellulose were analyzed by infrared spectrum. The reverse and vibration mode of cellulose was discussed. The absorption peak is basically in line with its theoretical calculating result. It is feasible that Terahertz Time Domain Spectroscopy can detect cellulose, and it provides a new method for the detection and judgement of cellulose in plants. PMID- 27400506 TI - [Preparation and Characterization of Manganese and Fluorine Co-Modified Hydroxyapatite Composite Coating]. AB - Titanium and titanium alloys have been widely used as orthopedic, dental implants and cardiovascular stents owing to their superior physical properties. However, titanium surface is inherently bio-inert, thus could not form efficient osseointegration with surrounding bone tissue. Therefore, to improve the surface property of titanium implant is significantly important in clinical application. Manganese and fluorine co-doped hydroxyapatite (FMnHAP) coatings were prepared on titanium substrate by electrochemical deposition technique. The as-prepared coatings were examined by scanning electron microscope (SEM), energy-dispersive X ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) tests. The results indicated that the FMnHAP coatings take the morphology of nanoscale-villous-like, the composite coating becomes more compact. The FTIR test indicated that the symmetry of bending vibration modes of hydroxyl changed, simulated body fluid immersion test proved that the FMnHAP coatings had induce carbonate-apatite formation, indicating that the composite coating possess excellent biocompatibility. In the electrochemical corrosion testing, the FMnHAP coatings showed stronger corrosion resistance than pure Ti. PMID- 27400507 TI - [Study on Estimation of Deserts Soil Total Phosphorus Content by Vis-NIR Spectra with Variable Selection]. AB - In this paper, 300 samples of desert soil collected in the Ebinur Lake Wetland Nature Reserve of Xinjiang were used as the research subject, and the visible/near-infrared spectra data about the soil obtained with the ASD Field Spec 3 HR spectrometer and the data about total phosphorus in the soil obtained through chemical analysis were used as the data sources; following Savizky-Golay smoothing, standard normal variation transformation and the first-order differential pretreatment, the combination of ant colony optimization interval partial least squares (ACO-iPLS) and genetic algorithm interval partial least squares (GA-iPLS) were employed to extract the characteristic wavelengths of the total phosphorus content in desert soil, before the partial least squares regression model for predicting the total-phosphorus content in soil was constructed; and this model was compared with the full-spectrum partial least squares model, ACO-iPLS and GA-iPLS. According to the results: through filte- ring with ACO-iPLS, the total-phosphorus characteristic wavebands in the desert soil were 500-700, 1 101-1 300, 1 501-1 700, and 1 901-2 100 nm; through further variable selection with GA-iPLS, 13 effective wavelengths with the minimum colinearity were selected, which were respectively: 1621, 546, 1259, 573, 1572, 1527, 564, 1 186, 1 988, 1541, 2024, 1 118, and 1 191 nm. According to the comparison of modeling methods, the most accurate model was the one based on the characteristic variables selected with the combination of ACO-iPLS and GA-iPLS, followed by the ones with genetic algorithm, ant colony optimization algorithm and the full spectrum method. For the total phosphorus content in soil model established with the combination of ACO-iPLS and GA-iPLS, the root mean square error of cross validation (RMSECV) and the root mean square error of prediction (RMSEP) were respectively 0.122 and 0.108 mg x g(-1), and the related coefficient for cross validation (R(c)) and the related coefficient for prediction (R(p)) were 0.535 7 and 0.555 9, respectively. Therefore, it can be seen that the model constructed through Savizky-Golay smoothing, standard normal variation transformation and the first-order differential pretreatment and by using the combination of AGO-iPLS and GA-iPLS has simple structure, high prediction accuracy and good robustness, and can be used for estimating the total phosphorus content in desert soil. PMID- 27400508 TI - [Research on Resistant Starch Content of Rice Grain Based on NIR Spectroscopy Model]. AB - A new method based on near-infrared reflectance spectroscopy (NIRS) analysis was explored to determine the content of rice-resistant starch instead of common chemical method which took long time was high-cost. First of all, we collected 62 spectral data which have big differences in terms of resistant starch content of rice, and then the spectral data and detected chemical values are imported chemometrics software. After that a near-infrared spectroscopy calibration model for rice-resistant starch content was constructed with partial least squares (PLS) method. Results are as follows: In respect of internal cross validation, the coefficient of determination (R2) of untreated, pretreatment with MSC+1thD, pretreatment with 1thD+SNV were 0.920 2, 0.967 0 and 0.976 7 respectively. Root mean square error of prediction (RMSEP) were 1.533 7, 1.011 2 and 0.837 1 respectively. In respect of external validation, the coefficient of determination (R2) of untreated, pretreatment with MSC+ 1thD, pretreatment with 1thD+SNV were 0.805, 0.976 and 0.992 respectively. The average absolute error was 1.456, 0.818, 0.515 respectively. There was no significant difference between chemical and predicted values (Turkey multiple comparison), so we think near infrared spectrum analysis is more feasible than chemical measurement. Among the different pretreatment, the first derivation and standard normal variate (1thD+SNV) have higher coefficient of determination (R2) and lower error value whether in internal validation and external validation. In other words, the calibration model has higher precision and less error by pretreatment with 1thD+SNV. PMID- 27400509 TI - [Determination of Hard Rate of Alfalfa (Medicago sativa L.) Seeds with Near Infrared Spectroscopy]. AB - Alfalfa (Medicago sativa L.) is the most commonly grown forage crop due to its better quality characteristics and high adaptability in China. However, there was 20%-80% hard seeds in alfalfa which could not be identified easily from non hard seeds which would cause the loss of seed utilization value and plant production. This experiment was designed for 121 samples of alfalfa. Seeds were collected according to different regions, harvested year and varieties. 31 samples were artificial matched as hard rates ranging from 20% to 80% to establish a model for hard seed rate by near infrared spectroscopy (NIRS) with Partial Least Square (PLS). The objective of this study was to establish a model and to estimate the efficiency of NIRS for determining hard rate of alfalfa seeds. The results showed that the correlation coefficient (R2(cal)) of calibration model was 0.981 6, root mean square error of cross validation (RMSECV) was 5.32, and the ratio of prediction to deviation (RPD) was 3.58. The forecast model in this experiment presented the satisfied precision. The proposed method using NIRS technology is feasible for identification and classification of hard seed in alfalfa. A new method, as nondestructive testing of hard seed rate, was provided to theoretical basis for fast nondestructive detection of hard seed rates in alfalfa. PMID- 27400510 TI - [Authentication of Trace Material Evidence in Forensic Science Field with Infrared Microscopic Technique]. AB - In the field of forensic science, conventional infrared spectral analysis technique is usually unable to meet the detection requirements, because only very a few trace material evidence with diverse shapes and complex compositions, can be extracted from the crime scene. Infrared microscopic technique is developed based on a combination of Fourier-transform infrared spectroscopic technique and microscopic technique. Infrared microscopic technique has a lot of advantages over conventional infrared spectroscopic technique, such as high detection sensitivity, micro-area analysisand nondestructive examination. It has effectively solved the problem of authentication of trace material evidence in the field of forensic science. Additionally, almost no external interference is introduced during measurements by infrared microscopic technique. It can satisfy the special need that the trace material evidence must be reserved for witness in court. It is illustrated in detail through real case analysis in this experimental center that, infrared microscopic technique has advantages in authentication of trace material evidence in forensic science field. In this paper, the vibration features in infrared spectra of material evidences, including paints, plastics, rubbers, fibers, drugs and toxicants, can be comparatively analyzed by means of infrared microscopic technique, in an attempt to provide powerful spectroscopic evidence for qualitative diagnosis of various criminal and traffic accident cases. The experimental results clearly suggest that infrared microscopic technique has an incomparable advantage and it has become an effective method for authentication of trace material evidence in the field of forensic science. PMID- 27400511 TI - [The Identification of Lettuce Varieties by Using Unsupervised Possibilistic Fuzzy Learning Vector Quantization and Near Infrared Spectroscopy]. AB - To solve the noisy sensitivity problem of fuzzy learning vector quantization (FLVQ), unsupervised possibilistic fuzzy learning vector quantization (UPFLVQ) was proposed based on unsupervised possibilistic fuzzy clustering (UPFC). UPFLVQ aimed to use fuzzy membership values and typicality values of UPFC to update the learning rate of learning vector quantization network and cluster centers. UPFLVQ is an unsupervised machine learning algorithm and it can be applied to classify without learning samples. UPFLVQ was used in the identification of lettuce varieties by near infrared spectroscopy (NIS). Short wave and long wave near infrared spectra of three types of lettuces were collected by FieldSpec@3 portable spectrometer in the wave-length range of 350-2 500 nm. When the near infrared spectra were compressed by principal component analysis (PCA), the first three principal components explained 97.50% of the total variance in near infrared spectra. After fuzzy c-means (FCM). clustering was performed for its cluster centers as the initial cluster centers of UPFLVQ, UPFLVQ could classify lettuce varieties with the terminal fuzzy membership values and typicality values. The experimental results showed that UPFLVQ together with NIS provided an effective method of identification of lettuce varieties with advantages such as fast testing, high accuracy rate and non-destructive characteristics. UPFLVQ is a clustering algorithm by combining UPFC and FLVQ, and it need not prepare any learning samples for the identification of lettuce varieties by NIS. UPFLVQ is suitable for linear separable data clustering and it provides a novel method for fast and nondestructive identification of lettuce varieties. PMID- 27400512 TI - [Discriminant Analysis of Lavender Essential Oil by Attenuated Total Reflectance Infrared Spectroscopy]. AB - This work aimed to use attenuated total reflectance Fourier transform infrared spectroscopy to identify the lavender essential oil by establishing a Lavender variety and quality analysis model. So, 96 samples were tested. For all samples, the raw spectra were pretreated as second derivative, and to determine the 1 750 900 cm(-1) wavelengths for pattern recognition analysis on the basis of the variance calculation. The results showed that principal component analysis (PCA) can basically discriminate lavender oil cultivar and the first three principal components mainly represent the ester, alcohol and terpenoid substances. When the orthogonal partial least-squares discriminant analysis (OPLS-DA) model was established, the 68 samples were used for the calibration set. Determination coefficients of OPLS-DA regression curve were 0.959 2, 0.976 4, and 0.958 8 respectively for three varieties of lavender essential oil. Three varieties of essential oil's the root mean square error of prediction (RMSEP) in validation set were 0.142 9, 0.127 3, and 0.124 9, respectively. The discriminant rate of calibration set and the prediction rate of validation set had reached 100%. The model has the very good recognition capability to detect the variety and quality of lavender essential oil. The result indicated that a model which provides a quick, intuitive and feasible method had been built to discriminate lavender oils. PMID- 27400513 TI - [The Identification of the Origin of Chinese Wolfberry Based on Infrared Spectral Technology and the Artificial Neural Network]. AB - The Fourier Transform Infrared Spectroscopy (FTIR) is established to find the geographic origins of Chinese wolfberry quickly. In the paper, the 45 samples of Chinese wolfberry from different places of Qinghai Province are to be surveyed by FTIR. The original data matrix of FTIR is pretreated with common preprocessing and wavelet transform. Compared with common windows shifting smoothing preprocessing, standard normal variation correction and multiplicative scatter correction, wavelet transform is an effective spectrum data preprocessing method. Before establishing model through the artificial neural networks, the spectra variables are compressed by means of the wavelet transformation so as to enhance the training speed of the artificial neural networks, and at the same time the related parameters of the artificial neural networks model are also discussed in detail. The survey shows even if the infrared spectroscopy data is compressed to 1/8 of its original data, the spectral information and analytical accuracy are not deteriorated. The compressed spectra variables are used for modeling parameters of the backpropagation artificial neural network (BP-ANN) model and the geographic origins of Chinese wolfberry are used for parameters of export. Three layers of neural network model are built to predict the 10 unknown samples by using the MATLAB neural network toolbox design error back propagation network. The number of hidden layer neurons is 5, and the number of output layer neuron is 1. The transfer function of hidden layer is tansig, while the transfer function of output layer is purelin. Network training function is trainl and the learning function of weights and thresholds is learngdm. net. trainParam. epochs=1 000, while net. trainParam. goal = 0.001. The recognition rate of 100% is to be achieved. It can be concluded that the method is quite suitable for the quick discrimination of producing areas of Chinese wolfberry. The infrared spectral analysis technology combined with the artificial neural networks is proved to be a reliable and new method for the identification of the original place of Traditional Chinese Medicine. PMID- 27400514 TI - [Baseline Correction Algorithm for Raman Spectroscopy Based on Non-Uniform B Spline]. AB - As one of the necessary steps for data processing of Raman spectroscopy, baseline correction is commonly used to eliminate the interference of fluorescence spectra. The traditional baseline correction algorithm based on polynomial fitting is simple and easy to implement, but its flexibility is poor due to the uncertain fitting order. In this paper, instead of using polynomial fitting, non uniform B-spline is proposed to overcome the shortcomings of the traditional method. Based on the advantages of the traditional algorithm, the node vector of non-uniform B-spline is fixed adaptively using the peak position of the original Raman spectrum, and then the baseline is fitted with the fixed order. In order to verify this algorithm, the Raman spectra of parathion-methyl and colza oil are detected and their baselines are corrected using this algorithm, the result is made comparison with two other baseline correction algorithms. The experimental results show that the effect of baseline correction is improved by using this algorithm with a fixed fitting order and less parameters, and there is no over or under fitting phenomenon. Therefore, non-uniform B-spline is proved to be an effective baseline correction algorithm of Raman spectroscopy. PMID- 27400515 TI - [Study on the Recognition of Liquor Age of Gujing Based on Raman Spectra and Support Vector Regression]. AB - It is an important and difficult research point to recognize the age of Chinese liquor rapidly and exactly in the field of liquor analyzing, which is also of great significance to the healthy development of the liquor industry and protection of the legitimate rights and interests of consumers. Spectroscopy together with the pattern recognition technology is a preferred method of achieving rapid identification of wine quality, in which the Raman Spectroscopy is promising because of its little affection of water and little or free of sample pretreatment. So, in this paper, Raman spectra and support vector regression (SVR) are used to recognize different ages and different storing time of the liquor of the same age. The innovation of this paper is mainly reflected in the following three aspects. First, the application of Raman in the area of liquor analysis is rarely reported till now. Second, the concentration of studying the recognition of wine age, while most studies focus on studying specific components of liquor and studies together with the pattern recognition method focus more on the identification of brands or different types of base wine. The third one is the application of regression analysis framework, which cannot be only used to identify different years of liquor, but also can be used to analyze different storing time, which has theoretical and practical significance to the research and quality control of liquor. Three kinds of experiments are conducted in this paper. Firstly, SVR is used to recognize different ages of 5, 8, 16 and 26 years of the Gujing Liquor; secondly, SVR is also used to classify the storing time of the 8-years liquor; thirdly, certain group of train data is deleted form the train set and put into the test set to simulate the actual situation of liquor age recognition. Results show that the SVR model has good train and predict performance in these experiments, and it has better performance than other non-liner regression method such as the Partial Least Squares Regression (PLS) method, and can also be applied in the practice of liquor analysis. PMID- 27400516 TI - [Study on the Rapid Detection of Triazophos Residues in Flesh of Navel Orange by Using Surface-Enhanced Raman Scattering]. AB - Surface enhanced Raman spectroscopy (SERS) and quick pre-treatment technology were used to detect triazophos residues in flesh of navel orange. Quantitative analysis model was developed by partial least squares (PLS) algorithm. SERS of different concentration (0.5 to 20 mg x L(-1)) triazophos juice solution with flesh extract as the matrix were collected by laser Raman spectrometer. Three preprocessing methods such as normalization, MSC and SNV were used to optimize Raman signals and PLS models were set up. The results showed that minimum detection concentration for triazophos in navel orange below 0.5 mg L(-1). The model built with normalization pre-processing gave the best result; the values of correlation (R(p)) and Root mean square error of prediction set (RMSEP) were 1.38 and 0.976 6, respectively. The predict recoveries were 95.97%-103.18%, and the absolute values of relative errors were below 5%. T-test (t = -0.018) showed that there was no significant difference between the true values and prediction values. This study demonstrates that this method is accurate and reliable. PMID- 27400517 TI - [NIR-SERS Spectra Detection of Cytidine on Nano-Silver Films]. AB - The polyvinyl alcohol (PVA) protected silver glass-like nanostructure (PVA-Ag GNS) with high surface-enhanced Raman scattering (SERS) activity was prepared and employed to detect the near-infrared surface enhanced Raman scattering (NIR-SERS) spectra of cytidine aqueous solution (10(-2)-10(-8) mol x L(-1)). In the work, the near-infrared laser beam (785 nm) was used as the excitation light source. The experiment results show that high-quality NIR-SERS spectra were obtained in the ranges of 300 to 2 000 cm(-1) and the detection limit of cytidine aqueous solution was down to 10(-7) mol x L(-1). Meanwhile, the PVA-Ag-GNS shows a high enhancement factor (EF) of -10(8). In order to test the optical reproducibility of PVA-Ag-GNS, ten samples of cytidine aqueous solution (10(-2)-10(-5) mol x L( 1)) had been dropped onto the surface of PVA-Ag-GNS respectively. Meanwhile, these samples were measured by the portable Raman spectrometer. As a result, the PVA-Ag-GNS demonstrated good optical reproducibility in the detection of cytidine aqueous solution. In addition, to explain the reason of enhancement effect, the ultraviolet-visible (UV-Vis) extinction spectrum and scanning electron microscope (SEM) of cytidine molecules adsorbed on the surface of PVA-Ag-GNS were measured. There is plasmon resonance band at 800 nm in the UV-Vis extinction Spectrum of the compound system. Therefore, when the near-infrared laser beam (785 nm) was used as excitation light source, the compound system may produce strongly surface plasmon resonance (SPR). According to the SEM of PVA-Ag-GNS, there are much interstitial between the silver nanoparticles. So NIR-SERS is mainly attributed to electromagnetic (EM) fields associated with strong surface plasmon resonance. At last, the geometry optimization and pre-Raman spectrum of cytidine for the ground states were performed with DFT, B3LYP functional and the 6-311G basis set, and the near-infrared laser with wavelength of 785 nm was employed in the pre Raman spectrum calculation process. The calculation results without imaginary frequency and the results match pretty well with the experimental Raman spectrum. At the same time, the assignations of Raman bands and adsorption behaviors of cytidine molecules on the surface of PVA-Ag-GNS are also discussed. According to our experiment and calculations, cytidine molecules mainly adsorbed on silver nanoparticles via the ribose moiety and amino group may get close to the local electromagnetic field. PMID- 27400518 TI - [Application of Cationic Aluminum Phthalocyanine, a Red-Emitting Fluorescent Probe, for Sensitive Quantitative Analysis of RNA at Nanogram Level]. AB - Tetrasubstituted trimethyl ammonium iodide aluminum phthalocyanine (TTMAAlPc), a positively charged phthalocyanine compound, is an emerging and potentially useful red-emitting fluorescence probe. The study showed that the fluorescence of TTMAAlPc could be quenched by RNA with high efficiency in weak alkaline media, and the degree of quenching has a linear relationship with RNA in a wide concentration range. The mechanism of quenching behavior of RNA on TTMAAlPc was discussed. It was attributed by the static interaction between RNA and TTMAAlPc, and the assembly of TTMAAlPc induced by RNA. Based on this new discovery, a novel method for quantitative determination of RNA at nanogram level has been established. The factors, including the pH of medium, buffer system, reaction time, reaction temperature, the usage of TTMAAlPc as well as the interferences, which affected the determination, were investigated and discussed. Under optimum conditions, the linear range of the calibration curve was 7.71-1 705.57 ng x mL( 1). The detection limit for RNA was 1.55 ng x mL(-1). This method has been applied to the analysis of practical samples with satisfied results. The constructed method is of high sensitivity and has a wide linear range, it also showed strong ability in the tolerance of foreign substances from anions, cations, surfactants and vitamins, all of which are common interferences encountered in the determination of RNA. Besides, it is the first report that the fluorescence quantum yield of TTMAAlPc has been measured at different pH by reference method in this work. The achieved data indicated that the fluorescence quantum yield of TTMAAlPc is larger than 20% and it keeps constant in a wide range of acidity, implying that TTMAAlPc is a high-quality red-emitting fluorescence probe, it has great potential for practical applications, thus is worthy of further study. This work expands the application of phthalocyanine compound in analytical sciences. PMID- 27400519 TI - [The Establishment of the Method of the Fiber Optic Chemical Sensor Synchronous Absorption-Fluorescence]. AB - A new method of simultaneously measuring fiber-optic chemical sensor absorption spectrum and fluorescence spectrum is established. Make synchronous absorption fluorescence cuvette, establish synchronous absorption-fluorescence spectrometry instrumentation combined by fiber optic chemical sensor technology, measure the synchronous absorption-fluorescence spectrums of solutions of rhodamine B, vitamin B2 and vitamin B6, compared by absorption spectroscopy measured by traditional UV-Visible photometric method and fluorescence spectroscopy measured by traditional fluorescence method. Synchronous absorption-fluorescence method measure absorption spectrums and fluorescence spectrums the same to traditional photometric and fluorescence spectroscopy of rhodamine B, vitamin B2 and vitamin B6. The maximum wavelength of fluorescence intensity method has high accuracy relatively compared with fluorescence, but the maximum wavelength of absorption has a slight deviation. Synchronous absorption-fluorescence method means simultaneously measure the absorption spectrums and fluorescence spectrums of the fluorescent substance, making two spectrums to one. The method measured the maximum emission wavelength with high accuracy, though in measuring maximum absorption wavelength there is a slight deviation, but it is worth further studying. PMID- 27400520 TI - [Study on the Hydrothermal Synthesis and Fluorescence of LaF3 : Tb3+, Ce3+ Nanocrystals]. AB - LaF3 : Tba3+, Ce3+ nanocrystals were prepared with hydrothermal method with the help of cetyltrimethyl ammonium bromide (CTAB). The effects of pH values of the solution, Ce3+/Tb+ ratio value and reaction time on the luminescent properties were investigated. XRD analysis shows that the as-prepared samples possess hexagonal phase and their main diffraction peaks of samples are similar to the standard card (JCPDS 32-0483). Compared with pure LaF3, the main diffraction peaks of the doped samples have a slight shift, showing existing isomorphous substitution between La3+ and the doped rare earth ions in parent lattice of LaF3. It is found from TEM results that the as-prepared samples have good crystallinity and their average grain sizes change in the range of 20-50 nm. The excitation spectra indicate that the stronger excitation spectrum peaks exist at 250 nm, which is assigned to the transition of 4f --> 5d from Ce3+. When activated at 250 nm, all LaF3 : Tb3+, Ce3+ nanocrystals possess weak blue emission at 490 nm (electric dipole transition, 5D4 --> 7F6) and good green emission at 543 nm (magnetic dipole transition, 5D4 -->7F5). As the Ce3+/Tb+ ratio increases, the fluorescence intensities increase at first and then weaken, and reach the strongest green emission at n(Ce)3+ /n(Tb)3+ = 4. The pH values have some influence on the colors and intensities of the LaF3 : Tb3+, Ce3+ nanocrystals. The sample prepared at pH 9 presents the best color, while the one at pH 7 exhibits the strongest green emission. Besides, increasing reaction time is helpful to improve color purity of sample and enhance its green emission. PMID- 27400521 TI - [Intermolecular Interactions between Cytisine and Bovine Serum Albumin A Synchronous Fluorescence Spectroscopic Analysis and Molecular Docking Research]. AB - Cytisine (Cy) is one of the alkaloids that exist naturally in the plant genera Laburnum of the family Fabaceae. With strong bioactivities, Cy is commercialized for smoking cessation for years. In this work, the study of intermolecular interactions between Cy and bovine serum albumin (BSA) was performed by applying fluorescence spectroscopic methods under simulated physiological conditions. The mechanism of fluorescence quenching of BSA by Cy was also studied. Parameters such as bathing temperature, time and solution pH were investigated to optimize the fluorescence quenching. The binding type, binding ratio and binding constant between BSA and Cy were calculated by using the Stem-Volmer equation. Experimental results indicated that Cy can quench the fluorescent emission of BSA statically by forming a 1 : 1 type non-covalent complex and the binding constant is 5.6 x 10(3) L x mol(-1). Synchronous fluorescence spectral research shows Cy may affect the fluorescence emission of Trp residues of BSA. Furthermore, molecular docking is utilized to model the complex and probe the plausible quenching mechanism. It can be noted that the hydrogen bindings and hydrophobic interactions between Cy and BSA change the micro-environment of Trp213, which leads to the fluorescence quenching of BSA. PMID- 27400522 TI - [Particle Size and Number Density Online Analysis for Particle Suspension with Polarization-Differentiation Elastic Light Scattering Spectroscopy]. AB - The basic principle of polarization-differentiation elastic light scattering spectroscopy based techniques is that under the linear polarized light incidence, the singlely scattered light from the superficial biological tissue and diffusively scattered light from the deep tissue can be separated according to the difference of polarization characteristics. The novel point of the paper is to apply this method to the detection of particle suspension and, to realize the simultaneous measurement of its particle size and number density in its natural status. We design and build a coaxial cage optical system, and measure the backscatter signal at a specified angle from a polystyrene microsphere suspension. By controlling the polarization direction of incident light with a linear polarizer and adjusting the polarization direction of collected light with another linear polarizer, we obtain the parallel polarized elastic light scattering spectrum and cross polarized elastic light scattering spectrum. The difference between the two is the differential polarized elastic light scattering spectrum which include only the single scattering information of the particles. We thus compare this spectrum to the Mie scattering calculation and extract the particle size. We then also analyze the cross polarized elastic light scattering spectrum by applying the particle size already extracted. The analysis is based on the approximate expressions taking account of light diffusing, from which we are able to obtain the number density of the particle suspension. We compare our experimental outcomes with the manufacturer-provided values and further analyze the influence of the particle diameter standard deviation on the number density extraction, by which we finally verify the experimental method. The potential applications of the method include the on-line particle quality monitoring for particle manufacture as well as the fat and protein density detection of milk products. PMID- 27400523 TI - [Fast Detection of Camellia Sinensis Growth Process and Tea Quality Informations with Spectral Technology: A Review]. AB - The research achievements and trends of spectral technology in fast detection of Camellia sinensis growth process information and tea quality information were being reviewed. Spectral technology is a kind of fast, nondestructive, efficient detection technology, which mainly contains infrared spectroscopy, fluorescence spectroscopy, Raman spectroscopy and mass spectroscopy. The rapid detection of Camellia sinensis growth process information and tea quality is helpful to realize the informatization and automation of tea production and ensure the tea quality and safety. This paper provides a review on its applications containing the detection of tea (Camellia sinensis) growing status(nitrogen, chlorophyll, diseases and insect pest), the discrimination of tea varieties, the grade discrimination of tea, the detection of tea internal quality (catechins, total polyphenols, caffeine, amino acid, pesticide residual and so on), the quality evaluation of tea beverage and tea by-product, the machinery of tea quality determination and discrimination. This paper briefly introduces the trends of the technology of the determination of tea growth process information, sensor and industrial application. In conclusion, spectral technology showed high potential to detect Camellia sinensis growth process information, to predict tea internal quality and to classify tea varieties and grades. Suitable chemometrics and preprocessing methods is helpful to improve the performance of the model and get rid of redundancy, which provides the possibility to develop the portable machinery. Future work is to develop the portable machinery and on-line detection system is recommended to improve the further application. The application and research achievement of spectral technology concerning about tea were outlined in this paper for the first time, which contained Camellia sinensis growth, tea production, the quality and safety of tea and by-produce and so on, as well as some problems to be solved and its future applicability in modern tea industrial. PMID- 27400524 TI - [Study on Ammonia Emission Rules in a Dairy Feedlot Based on Laser Spectroscopy Detection Method]. AB - It needs on-line monitoring of ammonia concentration on dairy feedlot to disclose ammonia emissions characteristics accurately for reducing ammonia emissions and improving the ecological environment. The on-line monitoring system for ammonia concentration has been designed based on Tunable Diode Laser Absorption Spectroscopy (TDLAS) technology combining with long open-path technology, then the study has been carried out with inverse dispersion technique and the system. The ammonia concentration in-situ has been detected and ammonia emission rules have been analyzed on a dairy feedlot in Baoding in autumn and winter of 2013. The monitoring indicated that the peak of ammonia concentration was 6.11 x 10(-6) in autumn, and that was 6.56 x 10(-6) in winter. The concentration results show that the variation of ammonia concentration had an obvious diurnal periodicity, and the general characteristic of diurnal variation was that the concentration was low in the daytime and was high at night. The ammonia emissions characteristic was obtained with inverse dispersion model that the peak of ammonia emissions velocity appeared at noon. The emission velocity was from 1.48 kg/head/hr to 130.6 kg/head/hr in autumn, and it was from 0.004 5 kg/head/hr to 43.32 kg/head/hr in winter which was lower than that in autumn. The results demonstrated ammonia emissions had certain seasonal differences in dairy feedlot scale. In conclusion, the ammonia concentration was detected with optical technology, and the ammonia emissions results were acquired by inverse dispersion model analysis with large range, high sensitivity, quick response without gas sampling. Thus, it's an effective method for ammonia emissions monitoring in dairy feedlot that provides technical support for scientific breeding. PMID- 27400525 TI - [Study on Kinetic of Hg2+ from Wastewater Absorbed by Lemon Residues]. AB - With low price and its superior adsorption performance after modification, currently agricultural waste is used as adsorbent of heavy metals in wastewater, which has become a hot research topic. To study on Hg2+ from wastewater absorbed by lemon residues that has been modified by 15% concentration of sulphuric acid. The pore volume, pore size and other properties of the adsorbent were test. The samples were characterized by differential thermal analysis, IR, electron microscopy and spectroscopy. The result showed that the adsorption rate was controlled by membrane diffusion kinetics that was viewed as the first order kinetics equation of the Lagergren, which was physically absorbed. The adsorption properties of modified lemon residues were improved greatly, and the pore size distribution mainly was medium. There were three losses-weight process. There was a endothermic peak around 66 degrees C and two exotherm near 316 degrees C and 494 degrees C. Basic framework of Lemon residues was not changed and structure of Lemon residues was amorphous; the surface of modified lemon residues loosen and many pores formed, and Hg2+ have been adsorbed effectively. PMID- 27400526 TI - [Study on the Visualization of the Biomass of Chlorella sp., Isochrysis galbana, and Spirulina sp. Based on Hyperspectral Imaging Technique]. AB - Effective cultivation of the microalgae is the key issue for microalgal bio energy utilization. In nutrient rich culture conditions, the microalge have a fast growth rate, but they are more susceptible to environmental pollution and influence. So to monitor the the growth process of microalgae is significant during cultivating. Hyperspectral imaging has the advantages of both spectra and image analysis. The spectra contain abundant material quality signal and the image contains abundant spatial information of the material about the chemical distribution. It can achieve the rapid information acquisition and access a large amount of data. In this paper, the authors collected the hyperspectral images of forty-five samples of Chlorella sp., Isochrysis galbana, and Spirulina sp., respectively. The average spectra of the region of interest (ROI) were extracted. After applying successive projection algorithm (SPA), the authors established the multiple linear regression (MLR) model with the spectra and corresponding biomass of 30 samples, 15 samples were used as the prediction set. For Chlorella sp., Isochrysis galbana, and Spirulina sp., the correlation coefficient of prediction (r(pre)) are 0.950, 0.969 and 0.961, the root mean square error of prediction (RMSEP) for 0.010 2, 0.010 7 and 0.007 1, respectively. Finally, the authors used the MLR model to predict biomass for each pixel in the images of prediction set; images displayed in different colors for visualization based on pseudo-color images with the help of a Matlab program. The results show that using hyperspectral imaging technique to predict the biomass of Chlorella sp. and Spirulina sp. were better, but for the Isochrysis galbana visualization needs to be further improved. This research set the basis for rapidly detecting the growth of microalgae and using the microalgae as the bio-energy. PMID- 27400527 TI - [Hyperspectral Estimation of Apple Tree Canopy LAI Based on SVM and RF Regression]. AB - Leaf area index (LAI) is the dynamic index of crop population size. Hyperspectral technology can be used to estimate apple canopy LAI rapidly and nondestructively. It can be provide a reference for monitoring the tree growing and yield estimation. The Red Fuji apple trees of full bearing fruit are the researching objects. Ninety apple trees canopies spectral reflectance and LAI values were measured by the ASD Fieldspec3 spectrometer and LAI-2200 in thirty orchards in constant two years in Qixia research area of Shandong Province. The optimal vegetation indices were selected by the method of correlation analysis of the original spectral reflectance and vegetation indices. The models of predicting the LAI were built with the multivariate regression analysis method of support vector machine (SVM) and random forest (RF). The new vegetation indices, GNDVI527, ND-VI676, RVI682, FD-NVI656 and GRVI517 and the previous two main vegetation indices, NDVI670 and NDVI705, are in accordance with LAI. In the RF regression model, the calibration set decision coefficient C-R2 of 0.920 and validation set decision coefficient V-R2 of 0.889 are higher than the SVM regression model by 0.045 and 0.033 respectively. The root mean square error of calibration set C-RMSE of 0.249, the root mean square error validation set V-RMSE of 0.236 are lower than that of the SVM regression model by 0.054 and 0.058 respectively. Relative analysis of calibrating error C-RPD and relative analysis of validation set V-RPD reached 3.363 and 2.520, 0.598 and 0.262, respectively, which were higher than the SVM regression model. The measured and predicted the scatterplot trend line slope of the calibration set and validation set C-S and V S are close to 1. The estimation result of RF regression model is better than that of the SVM. RF regression model can be used to estimate the LAI of red Fuji apple trees in full fruit period. PMID- 27400528 TI - [Study on the Rapid Evaluation of Total Volatile Basic Nitrogen (TVB-N) of Mutton by Hyperspectral Imaging Technique]. AB - Total Volatile Basic Nitrogen (TVB-N) was usually taken as the physicochemical reference value to evaluate the mutton freshness. In order to explore the feasibility of hyperspectral (HSI) imaging technique to detect mutton freshness, 71 representative mutton samples were collected and scanned using a diffuse reflectance hyperspectral imaging (HSI) system in the Visible-Near infrared (NIR) spectral region (400-1 000 nm), and the chemical values of TVB-N content were determined using the semimicro Kjeldahl method according to the modified Chinese national standard. The representative spectra of mutton samples were extracted and obtained after selection of the region of interests (ROIs). The samples of calibration set and prediction set were divided at the ratio of 3 : 1 according to the content gradient method. Optimum HSI calibration models of the mutton (TVB N) were established and evaluated by comparing different spectral preprocessing methods and modeling methods, which included Stepwise Multiple Linear Regression (SMLR), Partial Least Squares Regression (PLSR) and Principal Component Regression (PCR) methods. The results are that through the utilization of Multiplicative Scatter Correction (MSC), first derivative, Savitzky-Golay (S-G) smoothing and mean-centering together, both PLSR and PCR were able to achieve quantitative detection of mutton TVB-N. As for the PLSR model of mutton TVB-N established, the spectral pretreatment methods chosen included MSC, first derivative, S-G (15,2) smoothing and mean-centering, and the latent variables (LVs) number used was 11. As for the calibration set of PLSR model of mutton TVB N, the correlation coefficient (r) and root mean square error of calibration (RMSEC) were 0.92 and 3.00 mg x (100 g)(-1), respectively. As for the prediction set of PLSR model of mutton TVB-N, the correlation coefficient (r), Root Mean Square Error of Prediction (RMSEP), and ratio of standard deviation to standard error of prediction (RPD) were 0.92, 3.46 mg x (100 g)(-1) and 2.35, respectively. The study demonstrated that the rapid and accurate analysis of TVB N, the key freshness attribute, could be implemented by using the hyperspectral imaging (HSI) technique. The study provides the basis for further rapid and non destructive detection of other mutton freshness attributes by using the hyperspectral imaging (HSI) technique, the improvement of current modeling effect of TVB-N content and the application involved of the technique in the practical production. PMID- 27400529 TI - [On-Orbit Multispectral Sensor Characterization Based on Spectral Tarps]. AB - The multispectral remote sensing technology has been a primary means in the research of biomass monitoring, climate change, disaster prediction and etc. The spectral sensitivity is essential in the quantitative analysis of remote sensing data. When the sensor is running in the space, it will be influenced by cosmic radiation, severe change of temperature, chemical molecular contamination, cosmic dust and etc. As a result, the spectral sensitivity will degrade by time, which has great implication on the accuracy and consistency of the physical measurements. This paper presents a characterization method of the degradation based on man-made spectral targets. Firstly, a degradation model is established in the paper. Then, combined with equivalent reflectance of spectral targets measured and inverted from image, the degradation characterization can be achieved. The simulation and on orbit experiment results showed that, using the proposed method, the change of center wavelength and band width can be monotored. The method proposed in the paper has great significance for improving the accuracy of long time series remote sensing data product and comprehensive utilization level of multi sensor data products. PMID- 27400530 TI - [Research on Temporal and Spatial Evolution of Reheating Double-Pulse Laser Induced Plasma]. AB - In order to investigate the emission enhancement mechanisms of reheating Double Pulse Laser-Induced Breakdown Spectroscopy (DP-LIBS), single pulse LIBS (SP-LIBS) and reheating DP-LIBS were carried out on an alloy steel sample respectively. The plasma emission was collected by an Echelle spectrometer with high resolution, while the plasma structure was monitored via fast-photography. The temporal and spatial evolutio ns of the plasma generated by SP-LIBS and reheating DP-LIBS were being studied. It is found that the plasma temperature in reheating DP-LIBS was higher than that of SP-LIBS, and there was a turning point for the decay rate of plasma temperature in reheating DP-LIBS when the delay time was equal to the interpulse time of DP-LIBS. Moreover, the inte nsity of the plasma image was increased by reheating DP-LIBS, and the height and width of the central region of the plasma were increased about 23.5% and 15.1% respectively. The results of spatial distribution showed that the intensity of Fe II and N I lines in the plasma were obviously enhanced by reheating DP-LIBS when the distance from the sample surface was larger than 0.6 mm. While the intensity enhancement for Fe I lines were little, even in some positio ns the intensity of Fe I lines decreased. The plasma temperature of double-pulse configuration was about 2 000 K higher than that of SP-LIBS, and a larger hot region in the plasma was generated. It is evidenced that the emission enhancement mechanisms in reheating DP-LIBS is that the second laser pulse re-excited the plasma induced by the first laser pulse, and the higher plasma temperature resulted from the re-exciting process. PMID- 27400531 TI - [Study on the Emission Spectrum of Hydrogen Production with Microwave Discharge Plasma in Ethanol Solution]. AB - Hydrogen is regarded as a kind of clean energy with high caloricity and non pollution, which has been studied by many experts and scholars home and abroad. Microwave discharge plasma shows light future in the area of hydrogen production from ethanol solution, providing a new way to produce hydrogen. In order to further improve the technology and analyze the mechanism of hydrogen production with microwave discharge in liquid, emission spectrum of hydrogen production by microwave discharge plasma in ethanol solution was being studied. In this paper, plasma was generated on the top of electrode by 2.45 GHz microwave, and the spectral characteristics of hydrogen production from ethanol by microwave discharge in liquid were being studied using emission spectrometer. The results showed that a large number of H, O, OH, CH, C2 and other active particles could be produced in the process of hydrogen production from ethanol by microwave discharge in liquid. The emission spectrum intensity of OH, H, O radicals generated from ethanol is far more than that generated from pure water. Bond of O H split by more high-energy particles from water molecule was more difficult than that from ethanol molecule, so in the process of hydrogen production by microwave discharge plasma in ethanol solution; the main source of hydrogen was the dehydrogenation and restructuring of ethanol molecules instead of water decomposition. Under the definite external pressure and temperature, the emission spectrum intensity of OH, H, O radicals increased with the increase of microwave power markedly, but the emission spectrum intensity of CH, C2 active particles had the tendency to decrease with the increase of microwave power. It indicated that the number of high energy electrons and active particles high energy electron energy increased as the increase of microwave power, so more CH, C2 active particles were split more thoroughly. PMID- 27400532 TI - [Study on Soil Elements Detection with Laser-Induced Breakdown Spectroscopy: A Review]. AB - Laser-induced breakdown spectroscopy (LIBS), as a kind of atomic emission spectroscopy, has been considered to be a future new tool for chemical analysis due to its unique features, such as no need of sample preparation, stand-off or remote analysis. What's more it can achieve fast and multi-element analysis. Therefore, LIBS technology is regarded as a future "SurperStar" in the field of chemical analysis and green analytical techniques. At present, rapid and accurate detection and prevention of soil contamination (mainly in pollutants of heavy metals and organic matter) is deemed to be a concerned and serious central issue in modern agriculture and agricultural sustainable development. In this paper, the reseach achievements and trends of soil elements detection based on LIBS technology were being reviewed. The structural composition and foundmental of LIBS system is first briefly introduced. And the paper offers a review of on LIBS applications and fruits including the detection and analysis of major element, nutrient element and heavy metal element. Simultaneously, some studies on soil related metials and fields are briefly stated. The research tendency and developing prospects of LIBS in soil detection are presented at last. PMID- 27400533 TI - [Study on the Identification of Geographical Indication Wuchang Rice Based on the Content of Inorganic Elements]. AB - Wuchang rice is a geographical indication product in China. Due to its high quality and low production, the phenome- non of fake is more and more serious. An effective identification method of Wuchang rice is urgent needed, for the maintenance of its brand image and interest of consumers. Base on the content of inorganic elements which are analyzed by ICP-AES and ICP-MS in rice, the identification model of Wuchang rice is studied combining with principal component analysis (PCA), Fisher discrimination and artificial neural network (ANN) in this paper. The effect on the identification of samples is poor through PCA, while the samples from Wuchang area and other areas can be identified accurately through Fisher discrimination and ANN. The average accurate identification ratio of training and verification set through Fisher discrimination is 93.5%, while the average accurate identification ratio through ANN is 96.4%. The ability to identify of ANN is better than Fisher discrimination. Wuchang rice can be identified accurately through the result of this research which provides a technology for the protection of geographical indications of this product. PMID- 27400534 TI - [Influence of the Experiment Energy Dispersive X-Ray Fluorescence Measurement of Uranium by Different Excitation Source]. AB - Aiming at the self-excitation effect on the interference of measurements which exist in the process of Energy dispersive X-ray fluorescence method for uranium measurement. To solve the problem of radioactive isotopes only used as excitation source in determination of uranium. Utilizing the micro X-ray tube to test Self excitation effect to get a comparison of the results obtained by three different uranium ore samples--109 Cd, 241 Am and Mirco X-ray tube. The results showed that self-excitation effect produced the area measure of characteristic X-ray peak is less than 1% of active condition, also the interference of measurements can be negligible. Photoelectric effect cross-section excited by 109 Cd is higher, corresponding fluorescence yield is higher than excited by 241 Am as well due to characteristics X-ray energy of 109 Cd, 22.11 & 24.95 KeV adjacent to absorption edge energy of L(alpha), 21.75 KeV, based on the above, excitation efficiency by 109 Cd is higher than 241 Am; The fact that measurement error excited by 241 Am is significantly greater than by 109 Cd is mainly due to peak region overlap between L energy peaks of uranium and Scattering peak of 241 Am, 26.35 keV, These factors above caused the background of measured Spectrum higher; The error between the uranium content in ore samples which the X-ray tube as the excitation source and the chemical analysis results is within 10%. Conclusion: This paper come to the conclusion that the technical quality of uranium measurement used X ray tube as excitation source is superior to that in radioactive source excitation mode. PMID- 27400535 TI - [Based on Curing Age of Calcined Coal Gangue Fine Aggregate Mortar of X-Ray Diffraction and Scanning Electron Microscopy Analysis]. AB - By using X-ray diffraction (XRD) and environmental scanning electron microscope (SEM) analysis method, we stud- ied the activity of coal gangue fine aggregate under different calcination temperature. In view of the activity of the highest 700 degrees C high temperature calcined coal gangue fine aggregate mortar of hydration products, microstructure and strength were discussed in this paper, and the change laws of mortar strength with curing age (3, 7, 14, 28, 60 and 90 d) growth were analyzed. Test results showed that coal gangue fine aggregate with the increase of calcination temperature, the active gradually increases. When the calcination temperature reaches 700 degrees C, the activity of coal gangue fine aggregate is the highest. When calcining temperature continues to rise, activity falls. After 700 degrees C high temperature calcined coal gangue fine aggregate has obvious ash activity, the active components of SiO2 and Al2 O3 can be with cement hydration products in a certain degree of secondary hydration reaction. Through on the top of the activity of different curing age 700 degrees C high temperature calcined coal gangue fine aggregate mortar, XRD and SEM analysis showed that with the increase of curing age, secondary hydration reaction will be more fully, and the amount of hydration products also gradually increases. Compared with the early ages of the cement mortar, the products are more stable hydration products filling in mortar microscopic pore, which can further improve the microstructure of mortar, strengthen the interface performance of the mortar. The mortar internal structure is more uniform, calcined coal gangue fine aggregate and cement mortar are more of a strong continuous whole, which increase the later strength of hardened cement mortar, 700 degrees C high temperature calcined coal gangue fine aggregate pozzolanic effect is obvious. PMID- 27400536 TI - [Research on an Equal Wavelength Spectrum Reconstruction Method of Interference Imaging Spectrometer]. AB - Interference imaging spectrometer is one of the most important equipments of Chang'E 1 satellite, which is applied to analysis the material composition and its distribution of the surface on the moon. At present, the spectral resolution of level 2B scientific data obtained by existing methods is 325 cm(-1). If we use the description way of wavelength resolution, various spectrum is different: the first band is 7.6 nm, the last band is 29 nm, which introduces two questions: (1) the spectral resolution description way mismatch with the way of ground spectral library used for calibration and comparison; (2) The signal-to-noise ratio of the spectra in the shortwave band is low due to the signal entering narrow band is little. This paper discussed the relationship between wavelength resolution and cut-off function based on the reconstruction model of CE-1 interference imaging spectrometer. It proposed an adjustable cut-off function changing with wavelength or wavelength resolution, while selected the appropriate Sinc function as apodization to realize the reconstruction of arbitrary specified wavelength resolution in the band coverage. Then we used this method to CE-1 on orbit 0B data to get a spectral image of 29 nm wavelength resolution. Finally, by using the signal-to-noise ratio, principal component analysis and unsupervised classification method on the reconstruction results with 2 grade science data from ground application system for comparison, the results showed that: signal-to noise ratio of the shortwave band increased about 4 times, and the average increased about 2.4 times, the classification based on the spectrum was consistent, and the quality of the data was greatly improved. So, EWSR method has the advantages that: (1) in the case of keeping spectral information steadiness, it can improve the signal-to-noise ratio of shortwave band spectrum though sacrificed part of spectral resolution; (2) it can achieve the spectral data reconstruction which can set arbitrary band position or specify any wavelength resolution within the band range. PMID- 27400537 TI - [The Research on Optic Fiber FBG Corrosion Sensor Based on the Analysis of the Spectral Characteristics]. AB - Aiming at meeting the need of aluminum corrosion monitoring in aerospace field, a pre-load type fiber grating corrosion sensor based on an aluminum thin tube structure is proposed. The corrosion sensor of aluminum alloy structure in service monitoring mechanism is studied, a theoretical model about the relation of FBG reflection spectral characteristics and aluminum thickness variation is also obtained. Optical fiber grating corrosion monitoring test system based on the capillary structure of aluminum alloy is constructed by acid-base environment. The problem of cross sensitivity of temperature and strain is solved by configuring an optical fiber grating which is not affected by strain and only sensitive to temperature inside the aluminum alloy tube. The results shows that he aluminum tube packaging design not only can sense the effects of corrosion on the mechanical properties, but also can interference shielding effect of corrosion on the tube optical fiber sensing device. With the deepening of the metal tube corrosion and aluminum alloy tube thickness gradually thinning, fiber grating reflective spectrum gradually shift to the short wavelength and the wall thickness and the grating center wavelength offset has a good monotonic relation. These characteristics can provide useful help to further research corrosion online monitoring based on optic fiber sensor. PMID- 27400538 TI - [Study on the Effects and Compensation Effect of Recording Parameters Error on Imaging Performance of Holographic Grating in On-Line Spectral Diagnose]. AB - To making the high resolution grating, a numerical calculation was used to analyze the effect of recording parameters on groove density, focal curve and imaging performance of the grating and their compensation. Based on Fermat' s principle, light path function and aberration, the effect on imaging performance of the grating was analyzed. In the case of fixed using parameters, the error of the recording angle has a greater influence on imaging performance, therefore the gain of the weight of recording angle can improve the accuracy of the recording angle values in the optimization; recording distance has little influence on imaging performance; the relative errors of recording parameters cause the change of imaging performance of the grating; the results indicate that recording parameter errors can be compensated by adjusting its corresponding parameter. The study can give theoretical guidance to the fabrication for high resolution varied line-space plane holographic grating in on-line spectral diagnostic and reduce the alignment difficulty by analyze the main error effect the imaging performance and propose the compensation method. PMID- 27400539 TI - [Research on Multi-Spectral Target Recognition System Based on the Magneto Optical Modulation]. AB - The technology of target recognition based on characteristic multi-spectrum has many advantages, such as strong detection capability and discriminating capability of target species. But there are some problems, it requires that you obtain the background spectrum as a priori knowledge, and it requires that the change of background spectrum is small with time. Thereby its application of real time object recognition is limited in the new environment, or the complex environment. Based on magneto-optical modulation and characteristic multi spectrum the method is designed, and the target is identified without prior access to the background spectrum. In order to achieve the function of the target information in the one acquisition time for tested, compared to conventional methods in terms of target detection, it's adaptability is better than before on the battlefield, and it is of more practical significance. Meanwhile, the magneto optical modulator is used to suppress the interference of stray light background, thereby improving the probability of target recognition. Since the magneto optical modulation provides incremental iterative target spectral information, therefore, even if the unknown background spectrum or background spectrum change is large, it can significantly improve the recognition accuracy of information through an iterative target spectrum. Different test targets back shimmering light intensity and background intensity values were analyzed during experiments, results showed that three targets for linearly polarized reflectance modulation is significantly stronger than the background. And it was of great influence to visible imaging target identification when measured target used camouflage color, but the system of polarization modulation type can still recognize target well. On this basis, the target range within 0.5 km x 2 km multi-wavelength characteristics of the target species were identified. When using three characteristic wavelengths, the probability of target identification significantly reduced at around 2km, when using four or five characteristic wavelength position, the probability of target identification reach up to more than 95.0%. Meanwhile, in order to reduce the calculation and improve the real time detection capability of the system, finally, four characteristic wavelengths was selected. So the system has a certain application value. PMID- 27400540 TI - [Analyzer Design of Atmospheric Particulate Matter's Concentration and Elemental Composition Based on beta and X-Ray's Analysis Techniques]. AB - Monitoring atmospheric particulate matter requires real-time analysis, such as particulate matter's concentrations, their element types and contents. An analyzer which is based on beta and X rays analysis techniques is designed to meet those demands. Applying beta-ray attenuation law and energy dispersive X-ray fluorescence analysis principle, the paper introduces the analyzer's overall design scheme, structure, FPGA circuit hardware and software for the analyzer. And the analyzer can measure atmospheric particulate matters' concentration, elements and their contents by on-line analysis. Pure elemental particle standard samples were prepared by deposition, and those standard samples were used to set the calibration for the analyzer in this paper. The analyzer can monitor atmospheric particulate matters concentration, 30 kinds of elements and content, such as TSP, PM10 and PM2.5. Comparing the measurement results from the analyzer to Chengdu Environmental Protection Agency's monitoring results for monitoring particulate matters, a high consistency is obtained by the application in eastern suburbs of Chengdu. Meanwhile, the analyzer are highly sensitive in monitoring particulate matters which contained heavy metal elements (such as As, Hg, Cd, Cr, Pb and so on). The analyzer has lots of characteristics through technical performance testing, such as continuous measurement, low detection limit, quick analysis, easy to use and so on. In conclusion, the analyzer can meet the demands for analyzing atmospheric particulate matter's concentration, elements and their contents in urban environmental monitoring. PMID- 27400541 TI - [Study on Strain Detection with Si Based on Bicyclic Cascade Optical Microring Resonator]. AB - Optical micro-ring resonator prepared on Silicon-On-Insulator (SOI) has high sensitivity, small size and low mode volume. Its high sensitivity has been widely applied to the optical information transmission and inertial navigation devices field, while it is rarely applied in the testing of Mechanics. This paper presents a cantilever stress/strain gauge with an optical microring resonator. It is proposed the using of radius change of ring waveguide for the sensing element. When external stress is put on the structure, the radius of the SOI ring waveguide will be subjected to variation, which causes the optical resonant parameters to change. This ultimately leads to a red-shift of resonant spectrum, and shows the excellent characteristics of the structure's stress/strain sensitivity. Designed a bicyclic cascade embedded optical micro-cavity structure, which was prepared by employing MEMS lithography and ICP etching process. The characteristic of stress/strain sensitivity was calculated theoretically. Two values of 0.185 pm x kPa(-1) and 18.04 pm x microstrain(-1) were obtained experimentally, which also was verified by theoretical simulations. Comparing with the single-loop micro-cavity structure, its measuring range and stress sensitivity increased by nearly 50.3%, 10.6%, respectively. This paper provides a new method to develop micro-opto-electromechanical system (MOEMS) sensors. PMID- 27400542 TI - Vibrational Spectroscopic Study of N-[4-[1-Hydroxy-2-[(1-Methyl Ethyl) Amino] Ethyl] Phenyl] Methane Sulfonamide. AB - The vibrational spectral analysis was carried out by using FT-Raman and FT-IR spectroscopy in the range 4 000-400 and 4 000-400 cm(-1) respectively, for N-[4 [1-hydroxy-2-[(1-methyl ethyl) amino] ethyl] phenyl] methane sulfonamide (HPAEPMS) molecule. Theoretical calculations were performed by ab initio Density Functional Theory (DFT) method using 6-31G(d, p) basis set. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution (PED). The results of the calculations were applied to simulated spectra of the title compound, which show excellent agreement. PMID- 27400543 TI - A Relative Humidity Pulse Approach to Observe Mass Transfer Processes Controlled by Bulk and Surface for Aerosols. AB - With combination of a pulse relative humidity (RH) controlling system and rapid scan vacuum FTIR technique, dynamic hygroscopicity of aerosol can be studied during pulse RH process. The time-resolved FTIR spectra can provide both water content of aerosols and water vapor amount of the aerosol ambient in sub-second time resolution. Experiments were performed on sodium nitrate, magnesium sulfate and magnesium nitrate aerosols. By comparing their hygroscopicity in pulse RH process and quasi-equilibrium state, for sodium nitrate aerosols, under time resolution of 0.12 s, we didn't see water transfer delay between aerosols and ambient environment. For magnesium sulfate aerosols, after gel formation, the water transfer speed is limited by the aerosol bulk phase. While for aged magnesium nitrate aerosols, non-soluble species generated and formed a film on the surface of aerosol particles, which slow down the water exchange rate between aerosols and ambient environment. This method turned out to be an efficient and convenient tool to elucidate the water transfer process controlled by bulk and surface for aerosols. PMID- 27400544 TI - The Fluorescent Properties of Dissolved Organic Matter and Assessment of Total Nitrogen in Overlying Water with Different Dissolved Oxygen Conditions. AB - This paper used excitation-emission matrix spectroscopy (EEMs) to probe the fluorescence properties of dissolved organic matter (DOM) in the overlying water with different dissolved oxygen (DO) conditions, investigating the relationship between protein-like fluorescence intensity and total nitrogen concentration. The resulting fluorescence spectra revealed three protein-like components (high excitation wavelength tyrosine, low-excitation wavelength tyrosine, low excitation wavelength tryptophan) and two fulvic-like components (ultraviolet fulvic-like components, visible fulvic-like components) in the overlying water. Moreover, the protein-like components were dominant in the overlying water's DOM. The fluorescence intensity of the protein-like components decreased significantly after aeration. Two of the protein-like components--the low-excitation wavelength tyrosine and the low-excitation wavelength tryptophan--were more susceptible to degradation by microorganisms within the degradable organic matter with respect to the high-excitation wavelength tyrosine. In contrast, the ultraviolet and visible fulvic-like fluorescence intensity increased along with increasing DO concentration, indicating that the fulvic-like components were part of the refractory organics. The fluorescence indices of the DOM in the overlying water were between 1.65-1.80, suggesting that the sources of the DOM were related to terrigenous sediments and microbial metabolic processes, with the primary source being the contribution from microbial metabolism. The fluorescence indices increased along with DO growth, which showed that microbial biomass and microbial activity gradually increased with increasing DO while microbial metabolism also improved, which also increased the biogenic components in the overlying water. The fluorescence intensity of the high-excitation wavelength tyrosine peak A showed a good linear relationship with the total nitrogen concentration at higher DO concentrations of 2.5, 3.5, and 5.5 mg x L(-1), with r2 being 0.956, 0.946, and 0.953, respectively. This study demonstrated that excitation-emission matrix spectroscopy can distinguish the transformation characteristics of the DOM and identify the linear relationship between the fluorescence intensity of the high excitation wavelength tyrosine peak A and total nitrogen concentration, thus providing a quick and effective technique and theoretical support for river water monitoring and water restoration. PMID- 27400545 TI - Spectral Analysis of Interaction between Human Telomeric G-Quadruplex and Liliflorin A, the First Lignan Derivative Interacted with G-Quadruplex DNA. AB - Human telomeric G-quadruplex is a four-stranded structure folded by guanines (G) via Hoogsteen hydrogen bonding. The ligands which stabilize the G-quadruplex are often telomerase inhibitors and may become antitumor agents. Here, the interaction between a lignan derivative liliflorin A and human telomeric sequence dGGG (TTAGGG)3G-quadruplex HTG21 were examined by CD, FRET, and NMR spectroscopic methods. In addition, Molecular Docking was used to study the binding of liliflorin A to dTAGGG (TTAGGG)3 G-quadruplex HTG23. The CD data showed that liliflorin A enhanced HTG21 T(m). The T(m) value of G-quadruplex was enhanced 3.2 degrees C by 4.0 MUmol x L(-1) liliflorin A in FRET. The NMR spectra of HTG21 showed vivid alteration after reacting with liliflorin A in 3 hours. Molecular Docking suggested liliflorin A bound to the wide groove of HTG23 at G9, G10, G16 and G17. Liliflorin A was the first lignan derivative that could stabilize HTG21 selectively and provided a new candidate for antitumor drug design targeting on human telomeric G-quadruplex. PMID- 27400546 TI - Study on the Comparisons of the Establishment of Two Mathematical Modeling Methods for Soil Organic Matter Content Based on Spectral Reflectance. AB - Existing prediction models of soil organic matter content (SOC) are restricted by some factors, such as sampling scale, soil type and spectral parameters of samples. Therefore, it is necessary to make a comparative analysis on larger scales to build a quantitative model with better feasibility and greater accuracy. A total of 225 soil samples were collected in an extensive region of the upper reaches of Heihe river basin. SOC and spectral reflectance were being measured. All the samples were divided into 2 subsets--a modeling subset (180 samples) and a validation subset (45 samples). Six indices were obtained through transformation of soil spectral reflectance (R), continuum-removal (CR), reciprocal (REC), logarithm of reciprocal (LR), first-order differential (FDR) and Kubelka-Munck transformation coefficient (K-M). To build the mathematical model of SOC with 12 spectral indices, two methods, i. e., stepwise linear regression and partial least-square regression were used based on the modeling subset, respectively; the validation subset is used for model evaluation. The results indicated that, (1) Regardless of different modeling methods, model between SOC and LR index was always the best among the 6 reflectance-related indices. LR was the best index for predicting SOC; (2) For the model based on the LR index, the accuracy of model using partial least-square regression method was better than that using stepwise linear regression method; (3) 225 samples were compared to verify the former available published SOC model. Both the predicted and measured values passed the mean value t-test, and the Pearson correlation coefficient reached 0.826. It shows that local prediction model can be applied to the research of predicting SOC in the larger scale. PMID- 27400547 TI - Working Together. PMID- 27400549 TI - "Jousting" in the Dental Arena. PMID- 27400548 TI - The Future of the Health Care Reform Law. PMID- 27400550 TI - Half of the Patients of a Local Community Health Center Have Urgent Dental Needs. PMID- 27400552 TI - How Cone Beam Computed Tomography Increases Endodontic Success. PMID- 27400551 TI - Prepare for Medical Emergencies. PMID- 27400553 TI - The Changing Nature of Dental Practice and Retirement. PMID- 27400554 TI - A Clinico-Pathologic Correlation. Diagnosis. Unicystic ameloblastoma (mural variant). PMID- 27400555 TI - Oral Submucosal Hemorrhage. PMID- 27400556 TI - The Current State of Irrigation in Endodontics. PMID- 27400557 TI - A Man for All Seasons. PMID- 27400558 TI - [AORTIC ANEURYSMS. THE SILENT ENEMIES]. AB - Aortic aneurysms are caused by a localized degeneration of the middle layer, which promotes the formation and progressive expansion of the aneurysm. In ascending thoracic aorta, usually have genetic cause, and intervene when they reach 5 to 5.5 cm in diameter. The downlink and abdominal aorta are associated with cardiovascular risk factors, especially age, smoking and hypertension. They are usually asymptomatic until rupture and diagnosis or is incidental or required before rupture performing an ultrasound scan in males over 65 who have been smokers. The alternative treatment to surgery in this location is with percutaneous self-expanding stent. PMID- 27400559 TI - [NOT AVAILABLE]. PMID- 27400561 TI - [Not Available]. PMID- 27400560 TI - [OPERATION TO SUBSTITUTE THE LUMBAR URETER. LOWERING OF THE RENAL VEINS]. AB - A new operation to lower the aortic anastomosis of the renal artery is de- scribed. This procedure allows the left Kidney to be lowered enough to enable repair after resections of the upper urinary tract. Renal hemodynamics were not altered and good results were obtained with no complications. PMID- 27400562 TI - [DISEASES AND ITS TYPES]. AB - With this conference, I intend to define what is the disease and its types explaining the criteria for classification according to different points of view, as the etiologic, teleological, social impact, spatial and temporal distribution, production mechanisms, risk factors, which affects organs, etc. As there are diseases that do not exist dedicate a final chapter of this dissertation to develop them. PMID- 27400563 TI - [Not Available]. PMID- 27400564 TI - [SYNERGISTIC ACTIVITY OF DEGUELIN AND FLUDARABINE IN PRIMARY CELLS FROM CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS (CLL) AND IN A CLL MURINE MODEL]. AB - Chronic lymphocytic leukemia (CLL), a malignancy of mature B cells, remains incurable with chemotherapy. Our aim was to test if deguelin, a natural rotenoid which inhibits PI3K/AKT, could enhance the sensitivity to fludarabine of CLL cells and explore the therapeutic potential of deguelin/fludarabine combination in the inbreed New Zealand Black (NZB) mouse model of CLL. Our results indicate that deguelin induced apoptosis in cells from CLL patients in culture and showed a moderate synergy with fludarabine in cytoprotective culture conditions. Orally administered deguelin was highly effective on resident neoplasic cells in the spleens of aged NZB mice and combined administration with fludarabine prolonged the survival and reduced tumor infiltration in young NZB mice trasplanted with syngenic leukemic cells maintaining a good toxicity profile. Deguelin capacity to induce apoptosis, counteract microenvironmental survival stimuli and synergize with fludarabine suggests its potential for the treatment of CLL. PMID- 27400565 TI - [Not Available]. PMID- 27400566 TI - [Not Available]. PMID- 27400567 TI - [Not Available]. PMID- 27400568 TI - [IRRITABLE BOWEL SYNDROME. NEW HORIZONS]. AB - Irritable bowel syndrome is a chronic disorder of complex genesis. Infections, indiscriminate use of antibiotics and bowel cleansing may affect the composition of the microbiota. Knowledge of host-microbiota interaction is important to deepen their pathogenesis and allow therapeutic modulation of the microbiota. The interaction between the microbiota, the immune system and the enteric nervous system is not yet well understood, but could be important in the pathophysiology of the disorder. New therapeutic possibilities found with prebiotics, probiotics, new painkillers and antibiotics such as rifaximin. The modification of the fecal microbiota by transplantation may become a future therapeutic option. PMID- 27400569 TI - [Not Available]. PMID- 27400570 TI - [AGING, HEALTH AND SOCIETY: CHALLENGES FOR NEXT DECADE]. AB - Main challenges that may appear in our country along next decade related with the aging process are discussed. First of these challenges must take into account demography changes. Absolute number and. rates of elderly people increases permanently and it will be so in the next future. To assume the UN slogan "active aging" could be a positive attitude, and in this way both, each individual and social collectives, must be involved. In relation with health challenges, chronic disease and disability are the two most important problems. Prevention and permanent searching attitude of efficient political health answers are two essential pillars. Challenges on the social field must be focussed on ageism. The main objective must be to fight against any form of age discrimination (ageism). Beside that educational policies oriented over professionals and citizens. Last group of challenges concerns to managers and politicians and must be focussed on the look for resources and educational promotion. PMID- 27400571 TI - [Not Available]. PMID- 27400572 TI - [ETHICS OF THE LIMITATION OF LIFE-SUSTAINING TREATMENTS]. AB - The development over the last half century of the Life Support Technologies and the advent of the Intensive Care Units, have raised a wide range of new problems for ethical reflection. It is not by chance that the birth of Bioethics coincided with the birth of the Intensive Care Units. The first and most important of these problems is the withholding or withdrawing of the life support measures. In this article it is argued that the decision to limit life-sustaining treatments may be justified in four different ways, according with the four bioethical principles: by the expressed will of the patient or his/her representative, considering the procedure "extraordinary" for them (principle of autonomy); due to the lack of efficacy of the technique in question, which makes it "non-indicated" or "contraindicated" (principle of non-maleficence); due to problems of efficiency in the distribution of resources, which can make "disproportionate" the cost/benefit ratio of an specific treatment (principle of justice); and finally, due to the lack of effectiveness of some therapeutic procedures in concrete situations, which makes them "futile" (principle of beneficence). PMID- 27400573 TI - [Not Available]. PMID- 27400574 TI - [LIMITATION OF THE THERAPEUTIC EFFORT: A CLINICAL PERSPECTIVE]. AB - There is a clear trend in the past years, dies in the environment of the patient's home. The seemingly paradoxical fact that the intensive care units are produced at the same time use them more and more, in an attempt by patients and relatives run down facilities that offer the most advanced technologies. In many cases the UCI can be considered as a therapeutic trial, which occasionally fails. At this moment occurs a fundamental step, from care to restore health to palliative care, whose main objective is to ensure the comfort of the patient. The practice of the limitation of the therapeutic effort, it is a common practice in.patients who die in the ICU, and scientific societies involved, have made recommendations aimed at that this process be carried out, wherever possible, with the knowledge of the family. A restful communication, with time to listen and ask, in an atmosphere of privacy, will reduce the emotional pressure and sequelae in relatives and doctors. PMID- 27400576 TI - [Not Available]. PMID- 27400575 TI - [PRENATAL DIAGNOSIS: EVOLUTION OF CLINICAL INDICATIONS AND THE SOCIETY IN THE PAST 30 YEARS]. AB - Here we report the results of prenatal diagnosis at the Hospital Universitario Ramon y Cajal since its opening in 1979 to 2010, establishing a parallelism between the different methodologies for screening and prenatal diagnosis, clinical indications, and demographic changes. It shows how the indications have varied as to the structure of the population did. These changes have been possible thanks to the fact that the screening and prenatal diagnosis methods have allowed it. Demonstrating, once again, how procedures evolve with technology and adapt to the demography. This evolution has allowed to make a more effective prenatal diagnosis because the clinical indications have been more precise what has allowed to detect the same number of fetuses with chromosomal abnormalities by performing less invasive procedures, which has led to an optimization of prenatal diagnosis saving resources and personnel and, above all, avoiding unnecessary fetal losses. PMID- 27400578 TI - [Not Available]. PMID- 27400577 TI - [TERTIARY PERITONITIS]. AB - Tertiary peritonitis is an intraabdominal infection that arises in some patients with secondary peritonitis, despite receiving appropriate treatment. Recently described, it is a syndrome of late peritonitis and we are still lacking a precise and widely adopted definition. Diagnosis is difficult and treatment is complex. Among other therapeutic efforts, this entity requires early and repeated surgical treatment, either on demand or scheduled laparotomy, or even laparostomy. Prognosis is poor, and mortality can reach up to 60% of patients. We present the most interesting aspects of this disease. PMID- 27400580 TI - [Not Available]. PMID- 27400579 TI - [Not Available]. PMID- 27400581 TI - [JULIAN CALLEJA AND CARLOS MARIA CORTEZO. TWO KEY FIGURES IN THE CENTENNIAL BUILDING THE ROYAL ACADEMY OF MEDICINE]. AB - In this year of 2014 we celebrate the centenary of the current building RANM, and remember the life and work of two of the leading figures, not only from the Academy but also the Spanish politics of the time: the doctors Julian Calleja and Carlos Maria Cortezo, whose work was essential for the building was erected as a permanent seat. PMID- 27400582 TI - [Not Available]. PMID- 27400583 TI - [MEDICINE: THE MAIN ENGINE OF THE GENERATION OF 1914]. AB - This text shows how the so-called generation of 1914 was mostly made of people from the scientific world, in the broadest sense of the term--from Physics and other experimental sciences to Biology, Medicine, the Humanities, Law and the Social Sciences. In the first third of the 20th century, this generation radically transformed the panorama of scientific research in Spain. In this process, physicians played an essential role. Spanish Medicine did not only become a productive experimental field, it also made of medical care a subject of national concern. PMID- 27400584 TI - [Not Available]. PMID- 27400585 TI - [Not Available]. PMID- 27400586 TI - [Diagnosis and treatment of prosthetic hip and knee joint infections]. AB - Successful replacement arthroplasty enhances the patient's functional capacity, alleviates pain and improves the quality of life. Prosthetic joint infection is one of the most dangerous complications following replacement arthroplasty. In cases of suspected prosthetic joint infection it is essential to consult with the prosthetic joint unit and abstain from starting antibiotics before the appropriate microbiological samples. The diagnosis is made on the basis of history, clinical picture, levels of inflammatory markers, synovial fluid cells and microbiological findings. The most common options of surgical treatment are early debridement and replacement of loose parts, and replacement of the prosthesis. Antimicrobial drug therapy will be planned according to the surgical mode of treatment and the causative bacterium. PMID- 27400587 TI - [Changes in consumption of blood products in Finland from 2007 to 2014]. AB - The Finnish Red Cross Blood Service (FRCBS) collects and distributes all cellular blood products in Finland. The use of red cells in Finland follows neither the aging of the Finnish population nor morbidity. The use of red blood cells has diminished 34% during the last 20 years and half of this decrease has taken place during the last three years. Use of platelet preparations per inhabitant in Finland clearly exceeds European median. An enhanced IT support for the blood supply chain is needed to maximize the effectiveness of use of blood products. PMID- 27400588 TI - [Pediatric orthopedic cervical spine problems]. AB - Treatment-requiring diseases of the cervical spine in children are rare. The most common cases requiring medical assessment and treatment are acute torticollis and various accidents. A torticollis having lasted for more than a week should be recognized, because it can be treated by skull traction. Cervical spine fractures in children under school age are very rare, the most common being a fracture of the base of the dens of the second cervical vertebra. Cervical spine instability is almost always associated with an underlying disease. PMID- 27400589 TI - [Diagnosis and follow-up observation of granulosa cell tumor of the ovary are becoming more precise]. AB - Granulosa cell tumor of the ovary is a rare, hormonally active ovarian cancer, typical symptoms of which include various gynecological bleeding disorders. Adult granulosa cell tumor is most commonly detected at stage I, whereupon the prognosis is good. The disease, however, recurs in one third of stage I patients and leads to death in half of these. Conventional cytotoxic agents may be ineffective in the treatment of relapsed tumors. Inhibin B and anti-Mullerian hormone have proven to be sensitive and accurate markers. Knowledge about the disease mechanisms has improved the diagnostics and follow-up observation of the patients. PMID- 27400590 TI - [Prophylactic platelet transfusions]. AB - The consumption of platelet products in Finland is exceptionally high. For the most part, platelets are transfused pre-operatively to thrombocytopenic patients in order to prevent hemorrhage. Most of the minor procedures could, however, be conducted even if the patients'platelet levels would be lower than usual. In cardiac surgery, platelets are used because of the hemorrhagic diathesis associated with platelet inhibitors. Platelet inhibitors will, however, also bind to transfused platelets, whereby instead of prophylactic platelet transfusions it would be more sensible to leave the thorax open and not carry out ineffective platelet transfusions until the effect of the inhibitors has run out. We outline the prophylactic use of platelets based on recent international clinical practice guidelines. PMID- 27400591 TI - [Osteoporosis: a clinical perspective]. AB - Osteoporosis is defined by decreased bone density and microarchitectural deterioration that predispose to fragility fractures. The WHO diagnostic criteria of osteoporosis require bone densitometry but treatment is possible on the basis of high clinical fracture risk and can be assessed by the FRAX risk algorithm. All those subject to fracture risk should be advised about proper basic treatment of osteoporosis, including exercise, prevention of falls, smoking cessation, avoidance of alcohol intake, and dietary or supplemental abundance of calcium and vitamin D. Underlying diseases must be studied after diagnosis of osteoporosis even if treatment is initiated without densitometry. When indicated, specific osteoporosis therapy includes bisphosphonates, denosumab, teriparatide, strontium ranelate or SERMs. In hypogonadism, gonadal steroids may be indicated alone or in addition to a specific treatment. Treatment effect and continuation are assessed after 2 to 5 years. PMID- 27400592 TI - [Severe trampoline injuries and their risk factors among children and the young]. AB - BACKGROUND: Although the majority of trampoline injuries in children are minor, severe injuries occur as well. METHODS: We have analyzed the risk factors, treatment and outcome of severe trampoline injuries treated in the Oulu University Hospital in children and the young between April and November 2105. RESULTS: There was a total of eight severe injuries. Five injuries involved a danger of death. Almost all severe trampoline injuries resulted from an unsuccessful trick. A safety net was in use in half of the cases. CONCLUSIONS: All cervical spine injuries would have been avoided provided that the children would have refrained from doing a somersault on the trampoline. PMID- 27400593 TI - [Myocardial infarction in a patient free of coronary artery disease]. AB - Triptans are widely used for treating migraine attacks. Their mechanism of action is attributable to cerebrovascular vasoconstriction. Vasoconstriction can occur also in the coronary arteries. Mild chest symptoms not related to myocardial ischemia have been reported among triptan users. Severe cardiovascular events have also been reported, but they are extremely rare. There are few observational studies focusing on the cardiovascular risks of triptans. Triptans are nevertheless considered contra-indicated in patients with coronary artery disease. We report a case of zolmitriptan-induced myocardial infarction in a patient free of coronary artery disease. PMID- 27400594 TI - [Not Available]. PMID- 27400595 TI - [Not Available]. PMID- 27400596 TI - [Not Available]. PMID- 27400597 TI - [Not Available]. PMID- 27400598 TI - [Not Available]. PMID- 27400599 TI - [Not Available]. PMID- 27400600 TI - [Not Available]. PMID- 27400601 TI - [Not Available]. PMID- 27400602 TI - [Not Available]. PMID- 27400603 TI - [Not Available]. PMID- 27400604 TI - [Not Available]. PMID- 27400605 TI - [Not Available]. PMID- 27400606 TI - [Not Available]. PMID- 27400607 TI - "Will bursary plan really fix nursing shortages"? PMID- 27400608 TI - New regulator's senior nurse targets staffing. PMID- 27400609 TI - Bursary consultation launched. PMID- 27400610 TI - First national whistleblowing policy launched. PMID- 27400611 TI - Call for NICE to promote more nurse-led integrated services. PMID- 27400612 TI - Nurse assessments reduce need for pre-surgery tests. PMID- 27400613 TI - Call for expanded practice nurse role to reduce 'GP-centric' care. PMID- 27400614 TI - RCN welcomes Welsh primary care funding. PMID- 27400615 TI - HCAs receiving extra training to develop skills and support PNs. PMID- 27400617 TI - First dual master's degree for mental health and adult nursing. PMID- 27400616 TI - Trust considers paying nurses agency rates. PMID- 27400618 TI - One of Britain's longest-serving nurses reflects on 60-year career. PMID- 27400619 TI - "All young people with cancer should receive specialist care". PMID- 27400620 TI - Improving pulmonary rehabilitation services. AB - The Clinical Audit of Pulmonary Rehabilitation Services in England and Wales was the first national audit of pulmonary rehabilitation services in England and Wales. Forming part of the National Chronic Obstructive Pulmonary Disease Audit Programme, it was commissioned by Healthcare Quality Improvement Programme and conducted by the Royal College of Physicians and British Thoracic Society. The audit was undertaken to geographically map pulmonary rehabilitation services and identify how they can improve. This article summarises the key findings of the audit, and its recommendations. PMID- 27400621 TI - Viral hepatitis: the clinical nurse specialist role. PMID- 27400622 TI - Primary immune deficiency in bronchiectasis. AB - The primary purpose of the immune system is to protect the body from infection. Failure of the immune system can lead to repeated infections. The aim of this review is to discuss primary immune deficiency (PID) and its relationship with bronchiectasis in adults. It examines treatment options for patients with PID and provides practical details of how nurses can empower these patients to reduce their risk of respiratory infections. PMID- 27400623 TI - Decontaminating breast pump kits: new guidance. AB - Various methods can be used to decontaminate breast pump milk collection kits and items related to infant feeding but they have some drawbacks and risks. In 2015, the Joint Working Group of the Healthcare Infection Society and Infection Prevention Society published guidance to support the safe decontamination of this equipment at home and in hospital. This article summarises its recommendations for health professionals to use and communicate to other groups, such as parents and carers. PMID- 27400624 TI - Providing empathetic care in nursing practice. AB - The fifth in our seven-part series on patient narrative explores empathy. We focus on a patient story relevant to all fields of nursing and raise key issues about how health professionals convey empathy to patients. PMID- 27400625 TI - 60 seconds with Karen Hill. PMID- 27400626 TI - A marathon, not a sprint. PMID- 27400627 TI - Speciation dynamics and biogeography of Neotropical spiral gingers (Costaceae). AB - Species can arise via the divisive effects of allopatry as well as due to ecological and/or reproductive character displacement within sympatric populations. Two separate lineages of Costaceae are native to the Neotropics; an early-diverging clade endemic to South America (consisting of ca. 16 species in the genera Monocostus, Dimerocostus and Chamaecostus); and the Neotropical Costus clade (ca. 50 species), a diverse assemblage of understory herbs comprising nearly half of total familial species richness. We use a robust dated molecular phylogeny containing most of currently known species to inform macroevolutionary reconstructions, enabling us to examine the context of speciation in Neotropical lineages. Analyses of speciation rate revealed a significant variation among clades, with a rate shift at the most recent common ancestor of the Neotropical Costus clade. There is an overall predominance of allopatric speciation in the South American clade, as most species display little range overlap. In contrast, sympatry is much higher within the Neotropical Costus clade, independent of node age. Our results show that speciation dynamics during the history of Costaceae is strongly heterogeneous, and we suggest that the Costus radiation in the Neotropics arose at varied geographic contexts. PMID- 27400628 TI - Present diversity of Galapagos leaf-toed geckos (Phyllodactylidae: Phyllodactylus) stems from three independent colonization events. AB - We re-examined the biogeography of the leaf-toed geckos (Phyllodactylus) endemic to the Galapagos Islands by analyzing for the first time samples of P. gilberti, a species endemic to Wolf island, in a phylogenetic framework. Our aim was to test the three-colonizations scenario previously proposed for these lizards and estimate the age of each colonization event. To achieve this we estimated simultaneously a species tree and divergence times with Bayesian methods. Our results supported the three-colonizations scenario. Similar to a previous hypothesis, the species tree obtained here showed that most species of Phyllodactylus are nested in a single clade with an age between 5.49 and 13.8Ma, whereas a second independent colonization corresponding to P. darwini from San Cristobal island occurred 3.03Ma ago. The species from Wolf island, P. gilberti, stems from a more recent colonization event (0.69Ma). Thus, present diversity of Galapagos leaf-toed geckos stems from three independent, asynchronous colonization events. As with other Galapagos organisms, the Pacific coast of South America seems to be the source for the founders of P. gilberti. PMID- 27400630 TI - Phylogeny and temporal diversification of the New World pond turtles (Emydidae). AB - We present a comprehensive multigene phylogeny and time tree for the turtle family Emydidae. Our phylogenetic analysis, based on 30 nuclear and four mitochondrial genes (23,330 total base pairs) sequenced for two individuals for each of the currently recognized species of the subfamily Emydinae and two species from each of the more species-rich Deirochelyinae genera, yielded a well supported tree that provides an evolutionary framework for this well-studied clade and a basis for a stable taxonomy. We calibrated an emydid time tree using three well-vetted fossils, modeled uncertainty in fossil ages to reflect their accuracy in node dating, and extracted stem/crown ages of a number of key diversification events. We date the age of crown emydids at a relatively young 44Ma, and the crown age of both contained subfamilies at roughly 30Ma. One deirochelyine clade, which includes the genera Graptemys, Malaclemys, Pseudemys, and Trachemys and contains 11% of all turtle species, dates to 21Ma just prior to the mid-Miocene climatic optimum, suggesting a potential causal link between warm, moist conditions and rapid species accumulation of these highly aquatic turtles. Both nuclear DNA data alone and in combination with mitochondrial DNA support the monophyly of an inclusive genus Emys containing the old world species orbicularis and trinacris and the New World blandingii, marmorata and pallida. Given that all members of this group were originally aligned in the genus Emys and that the age of the clade is roughly equal to other emydine genera, we strongly support a classification that places these five species in a single genus rather than the alternative three-genus scheme (Emys (orbicularis, trinacris), Actinemys (marmorata, pallida), Emydoidea (blandingii)). The phylogeny and resulting time tree presented here provides a comprehensive foundation for future comparative analyses of the Emydidae that will shed light on the historical ecology and conservation prioritization of this diverse chelonian clade. PMID- 27400629 TI - Comprehensive phylogeny, biogeography and new classification of the diverse bee tribe Megachilini: Can we use DNA barcodes in phylogenies of large genera? AB - Classification and evolutionary studies of particularly speciose clades pose important challenges, as phylogenetic analyses typically sample a small proportion of the existing diversity. We examine here one of the largest bee genera, the genus Megachile - the dauber and leafcutting bees. Besides presenting a phylogeny based on five nuclear genes (5480 aligned nucleotide positions), we attempt to use the phylogenetic signal of mitochondrial DNA barcodes, which are rapidly accumulating and already include a substantial proportion of the known species diversity in the genus. We used barcodes in two ways: first, to identify particularly divergent lineages and thus to guide taxon sampling in our nuclear phylogeny; second, to augment taxon sampling by combining nuclear markers (as backbone for ancient divergences) with DNA barcodes. Our results indicate that DNA barcodes bear phylogenetic signal limited to very recent divergences (3-4 my before present). Sampling within clades of very closely related species may be augmented using this technique, but our results also suggest statistically supported, but incongruent placements of some taxa. However, the addition of one single nuclear gene (LW-rhodopsin) to the DNA barcode data was enough to recover meaningful placement with high clade support values for nodes up to 15 million years old. We discuss different proposals for the generic classification of the tribe Megachilini. Finding a classification that is both in agreement with our phylogenetic hypotheses and practical in terms of diagnosability is particularly challenging as our analyses recover several well-supported clades that include morphologically heterogeneous lineages. We favour a classification that recognizes seven morphologically well-delimited genera in Megachilini: Coelioxys, Gronoceras, Heriadopsis, Matangapis, Megachile, Noteriades and Radoszkowskiana. Our results also lead to the following classification changes: the groups known as Dinavis, Neglectella, Eurymella and Phaenosarus are reestablished as valid subgenera of the genus Megachile, while the subgenus Alocanthedon is placed in synonymy with M. (Callomegachile), the subgenera Parachalicodoma and Largella with M. (Pseudomegachile), Anodonteutricharaea with M. (Paracella), Platysta with M. (Eurymella), and Grosapis and Eumegachile with M. (Megachile) (new synonymies). In addition, we use maximum likelihood reconstructions of ancestral geographic ranges to infer the origin of the tribe and reconstruct the main dispersal routes explaining the current, cosmopolitan distribution of this genus. PMID- 27400631 TI - Preoperative endoscopy may reduce the need for revisional surgery for gastro oesophageal reflux disease following laparoscopic sleeve gastrectomy. AB - Laparoscopic sleeve gastrectomy is a safe and effective bariatric operation, but postoperative reflux symptoms can sometimes necessitate revisional surgery. Roux en-Y gastric bypass is the preferred operation in morbidly obese patients with gastro-oesophageal reflux disease. In 2011, we introduced preoperative endoscopy to assess for hiatus hernia or evidence of oesophagitis in conjunction with an assessment of gastro-oesophageal reflux symptoms for all patients undergoing bariatric surgery with a view to avoid sleeve gastrectomy for these patients. A prospectively maintained database was used to identify patients who underwent sleeve gastrectomy before and after we changed the unit policy. The need for revisional surgery in patients with troublesome gastro-oesophageal reflux disease was examined. Prior to 2011, 130 patients underwent sleeve gastrectomy, and 11 (8.5%) of them required conversion to Roux-en-Y gastric bypass for symptomatic reflux disease. Following the policy change, 284 patients underwent sleeve gastrectomy, and to date, only five (1.8%) have required revisional surgery (p = 0.001). Baseline demographics were comparable between the groups, and average follow-up period was 47 and 33 months, respectively, for each group. Preoperative endoscopy and a detailed clinical history regarding gastro-oesophageal reflux symptoms may improve patient selection for sleeve gastrectomy. Avoiding sleeve gastrectomy in patients with reflux disease and/or hiatus hernia may reduce the incidence of revisional surgery. PMID- 27400632 TI - Unusual glycogenic hepatopathy causing abnormal liver enzymes in a morbidly obese adolescent with well-controlled type 2 diabetes: resolved after A1c was normalized by metformin. AB - We report, for the first time, a case of an accumulation of glycogen in the liver causing elevation of liver enzymes in a 15-year-old morbidly obese adolescent male with well-controlled type 2 diabetes. Notably, the patient did not have poorly controlled type 1 diabetes and did not require insulin. After normalization of the A1c with metformin, elevated liver enzymes returned to normal. PMID- 27400633 TI - How to prevent and treat complications of the retrograde approach to chronic total occlusion percutaneous coronary intervention. AB - The retrograde approach is important for achieving high success rates in chronic total occlusion percutaneous coronary intervention. Operators must be aware of complications that can occur during retrograde CTO PCI; they must continually try to prevent them and be ready to treat them, if they occur. Systematic, prospective study of complications in CTO PCI is needed for the development of additional preventive and treatment strategies. PMID- 27400634 TI - The bare naked truth... "excuse me but your metal is showing!". AB - In 11,181 consecutive STEMI patients, the use of DES increased over time and there were significant differences in patients who received DES versus BMS Using complex statistical modeling to adjust for measured and unmeasured confounders, the study provides real world data that the use of DES in STEMI is associated with reduced TVR and improved long-term survival Overwhelming evidence supports the use of current-generation DES as first line for STEMI. PMID- 27400635 TI - End of the bare metal stent era? AB - Second-generation drug eluting stents (2g-DES) have lower rates of stent thrombosis (ST) than bare metal stents (BMS). Second-generation DES have exceedingly low rates of very late ST, significantly improving on first generation drug eluting stents (1g-DES) and similar to BMS. Emerging drug-coated stent (DCS) technology appears superior to BMS in patients unable to tolerate prolonged dual antiplatelet therapy (DAPT). PMID- 27400636 TI - In early returns scoring scores big. AB - A scoring or cutting balloon is always useful in preventing slippage during therapy of in-stent restenosis. A drug-coated scoring balloon for in-stent restenosis may be an alternative to a drug-coated balloon Definitive comparison trials are needed and likely to help define their exact role in patients with in stent restenosis. PMID- 27400637 TI - Coronary bifurcations in clinical practice: Tell me what we can do better. AB - In bifurcation lesion, a precise evaluation of lesion severity and disease extension requires the use of bifurcation (three branches) quantitative coronary angiography. The use of Intravascular imaging to guide PCI in bifurcation has shown to reduce clinical events. Selection and duration of the dual antiplatelet therapy after bifurcation lesion PCI require further investigation. PMID- 27400638 TI - Saphenous vein bypass graft intervention and embolic protection devices: Time for reassessment (and revision of percutaneous coronary intervention guidelines). AB - Professional societies recommend embolic protection devices (EPDs) during percutaneous intervention of saphenous vein bypass grafts (SVGs; class I, level of evidence B). Practice patterns indicate that 21% of SVG interventions are performed with EPDs. Despite a single randomized trial that demonstrated efficacy for EPDs, other studies suggest that the benefits of EPDs are controversial. Consideration should be given toward performing a contemporary EPD trial to incorporate new technologies and pharmacotherapies; in the meantime, guideline recommendations for use of EPDs should be downgraded. PMID- 27400639 TI - Ablation or surgery for medically refractory HCM. Updating an imperfect dataset. AB - Retrospective comparison of alcohol septal ablation with surgical myectomy suggests that although there is a greater reduction in LVOT gradient with surgical myectomy, symptom relief and survival are similar between the two treatment strategies. In patients who don't have an anatomic indication for surgical myectomy, alcohol septal ablation appears to be a safe and effective alternative. Patients with medication-refractory HOCM require a multi disciplinary assessment, which is best performed at specialized treatment centers, to assess which therapy is best suited to treat them. PMID- 27400640 TI - Size does matter but is there an obesity paradox in TAVR? AB - Patients with low body mass index (<20 kg/m(2) ) undergoing transcatheter aortic valve replacement have higher short- and long-term mortality Low BMI is an important tool to consider in patient screening and prognostication Prospective study is needed to accurately assess the effects of BMI in TAVR patients, to prove or refute the obesity paradox. PMID- 27400642 TI - Simultaneous detection of 93 synthetic cannabinoids by liquid chromatography tandem mass spectrometry and retrospective application to real forensic samples. AB - The Internet is flooded with steadily changing synthetic cannabinoids in 'Spice' products. In routine forensic work, it is difficult to keep the analytical methods for the detection of these analytes up to date. We describe a liquid chromatography-tandem mass spectrometry method after liquid-liquid extraction for the detection of 93 synthetic cannabinoids in human serum. The method was validated for selectivity and specificity, matrix effects, and analytical limits (<1 ng/mL for 81 substances) for qualitative analysis. A short quantitative validation regarding linearity and precision data was also conducted. The method was applied to 189 serum samples provided by police authorities. Sixty-four samples (33.8%) were found positive for at least one synthetic cannabinoid, whereby MDMB-CHMICA, AB-CHMINACA, and 5 F-PB-22 were the substances most frequently detected. Consumption of these substances and plasma concentrations are linked to symptoms documented by the police. Six case reports are presented. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27400643 TI - The antibiotic pipeline for multi-drug resistant gram negative bacteria: what can we expect? AB - INTRODUCTION: A real concern in the medical community is the increasing resistance of bacteria, especially that of Gram-negative types. New antibiotics are currently under clinical development, promising to tackle severe infections caused, especially, by multi-drug resistant (MDR) bacteria and broaden the armamentarium of clinicians. AREAS COVERED: We searched PUBMED and GOOGLE databases. Combinations of already approved beta-lactams or monobactams with new beta-lactamase inhibitors [imipenem-cilastatin/MK-7655 (relebactam), meropenem/RPX7009 (vaborbactam), ceftaroline/avibactam, aztreonam/avibactam], new beta-lactams (S-649266, BAL30072), aminoglycosides (plazomicin), quinolones (finafloxacin) and tetracyclines (eravacycline) were included in the review. Expert commentary: For the majority of the upcoming antibiotics the currently available data is limited to their microbiology and pharmacokinetics. Their effectiveness and safety against infections due to MDR bacteria remain to be proved. Significant issues are also the impact of these antibiotics on the human intestinal microbiota and their possible co-administration with already-known antimicrobial agents in difficult-to-treat-infections; further studies should be conducted for these objectives. PMID- 27400644 TI - Sludge reduction using aquatic worms under different aeration regimes. AB - Adding aquatic worms to a wastewater treatment system can reduce sludge production through predation. The aeration level is crucial for success. To evaluate aeration impacts on sludge reduction and determine an optimal aeration regime, this study investigated the processes of in-situ sludge reduction, using aquatic worms exposed to different aeration levels. The experiment also compared treatment results between a conventional reactor and an aquatic worm reactor (WR). Results indicated that the recommended concentration of dissolved oxygen (DO) was 2.5 mg L-1. The removal rate of chemical oxygen demand remained steady at 80% when the DO concentration was higher than 2.5 mg L-1, while the removal rate of ammonia nitrogen continued to moderately increase. Increasing the DO concentration to 5 mg L-1 did not improve sludge reduction, and consumed more power. With a DO concentration of 2.5 mg L-1 and a power of 0.19 kWh t-1 water, the absolute sludge reduction and relative sludge reduction rates in the WR were 60.0% and 45.7%, respectively, and the daily aquatic worm growth rate was 0.150 d 1 during the 17-d test. Therefore, at the recommended aeration regime, aquatic worms reduced the sludge without increasing the power consumption or deteriorating the effluent. PMID- 27400646 TI - Synthesis and Properties of [7]Helicene-like Compounds Fused with a Fluorene Unit. AB - [7]Helicene-like compounds with a fluorene unit were successfully synthesized using a platinum-catalyzed double cyclization reaction. Crystal structures and photophysical properties of these compounds were also studied. In particular, they were found to exhibit a high fluorescence quantum yield and a relatively large g value (dissymmetric factor) of circularly polarized luminescence (CPL) for small molecules. PMID- 27400647 TI - An efficient perovskite solar cell with symmetrical Zn(ii) phthalocyanine infiltrated buffering porous Al2O3 as the hybrid interfacial hole-transporting layer. AB - A new Zn(ii) phthalocyanine (Pc) based low bandgap HTM is introduced for perovskite solar cells. Steady state and time-resolved photoluminescence (PL) measurements indicated an evenly matched hole extraction efficiency between sym HTPcH and spiro-OMeTAD. On account of the low film quality and resulting high recombination, Zn(ii) Pc normally cannot work as an effective HTM. We adopted insulating Al2O3 for the infiltration of sym-HTPcH to form a hybrid interfacial buffer layer, affording perovskite solar cells (PSCs) with an average PCE value of up to 12.3%, which is a significant improvement with respect to the control cell without the meso-Al2O3 layer (4.21%) and is the highest value ever reported for Zn(ii) phthalocyanine based devices under AM1.5G standard conditions. A hysteresis test revealed that our device structure with the new HTM exhibited a balanced charge extraction behaviour. PMID- 27400648 TI - Permselective 2D-polymer-based membrane tuneable by host-guest chemistry. AB - A permselective membrane with a non-covalently tailorable surface has been fabricated by deposition of a cucurbit[6]uril-based 2D polymer film onto a simple support membrane. Tuneable permselectivity of this membrane has been achieved through non-covalent surface modification using the remarkable host-guest chemistry of the incorporated cucurbit[6]uril units. PMID- 27400645 TI - Risk stratification of prostate cancer: integrating multiparametric MRI, nomograms and biomarkers. AB - Accurate risk stratification of prostate cancer is achieved with a number of existing tools to ensure the identification of at-risk patients, characterization of disease aggressiveness, prediction of cancer burden and extrapolation of treatment outcomes for appropriate management of the disease. Statistical tables and nomograms using classic clinicopathological variables have long been the standard of care. However, the introduction of multiparametric MRI, along with fusion-guided targeted prostate biopsy and novel biomarkers, are being assimilated into clinical practice. The majority of studies to date present the outcomes of each in isolation. The current review offers a critical and objective assessment regarding the integration of multiparametric MRI and fusion-guided prostate biopsy with novel biomarkers and predictive nomograms in contemporary clinical practice. PMID- 27400649 TI - Surgical treatment: Myomectomy and hysterectomy; Endoscopy: A major advancement. AB - Uterine fibroids affect 25% of women worldwide. Symptomatic women can be treated by either medical or surgical treatment. Development of endoscopic surgery has widely changed the management of myoma. Currently, although laparoscopic or laparoscopic robot-assisted myomectomies or hysterectomies are common, there has been no consensual guideline concerning the surgical techniques, operative route, and usefulness of preoperative treatment. Hysteroscopy management is a major advancement avoiding invasive surgery. This study deals with a literature review concerning surgical management of fibroids. PMID- 27400650 TI - Natural selection in the colloid world: active chiral spirals. AB - We present a model system in which to study natural selection in the colloid world. In the assembly of active Janus particles into rotating pinwheels when mixed with trace amounts of homogeneous colloids in the presence of an AC electric field, broken symmetry in the rotation direction produces spiral, chiral shapes. Locked into a central rotation point by the centre particle, the spiral arms are found to trail rotation of the overall cluster. To achieve a steady state, the spiral arms undergo an evolutionary process to coordinate their motion. Because all the particles as segments of the pinwheel arms are self propelled, asymmetric arm lengths are tolerated. Reconfiguration of these structures can happen in various ways and various mechanisms of this directed structural change are analyzed in detail. We introduce the concept of VIP (very important particles) to express that sustainability of active structures is most sensitive to only a few particles at strategic locations in the moving self assembled structures. PMID- 27400651 TI - Efficacy of preoperative biliary drainage in malignant obstructive jaundice: a meta-analysis and systematic review. AB - BACKGROUND: In patients requiring surgical resection for malignant biliary jaundice, it is unclear if preoperative biliary drainage (PBD) would improve mortality and morbidity by restoration of biliary flow prior to operation. This is a meta-analysis to pool the evidence and assess the utility of PBD in patients with malignant obstructive jaundice. The primary outcome is comparing mortality outcomes in patients with malignant obstructive jaundice undergoing direct surgery (DS) versus PBD. The secondary outcomes include major adverse events and length of hospital stay in both the groups. METHODS: Studies using PBD in patients with malignant obstructive jaundice were included in this study. For the data collection and extraction, articles were searched in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, etc. Pooled proportions were calculated using both Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). RESULTS: Initial search identified 2230 reference articles, of which 204 were selected and reviewed. Twenty-six studies (N = 3532) for PBD in malignant obstructive jaundice which met the inclusion criteria were included in this analysis. The odds ratio for mortality in PBD group versus DS group was 0.96 (95 % CI = 0.71 to 1.29). Pooled number of major adverse effects was lower in the PBD group at 10.40 (95 % CI = 9.96 to 10.83) compared to 15.56 (95 % CI = 15.06 to 16.05) in the DS group. Subgroup analysis comparing internal PBD to DS group showed lower odds for major adverse events (odds ratio, 0.48 with 95 % CI = 0.32 to 0.74). CONCLUSIONS: In patients with malignant biliary jaundice requiring surgery, PBD group had significantly less major adverse effects than DS group. Length of hospital stay and mortality rate were comparable in both the groups. PMID- 27400653 TI - Assessment of residual doses to population after decontamination in Fukushima Prefecture. AB - Large quantities of radioactive materials were released into the environment as a result of the Fukushima Daiichi Nuclear Power Station accident. Many inhabitants residing in the affected areas are now exposed to radiation in their daily lives. In an attempt to manage this radiation dose, an additional radiation dose of 1 mSv/y was adopted as a long-term dosimetric target. An activity level reading of 0.23 MUSv/h was then determined as a guidance value to achieve the target by implementing decontamination measures. The objectives of this study are to assess the effects of decontamination based on this guidance value and to predict any possible future problems with the decontamination strategy. Using a probabilistic approach, we assessed the annual effective dose of indoor workers, outdoor workers, and pensioners in the Fukushima Prefecture. Our probabilistic model considers the variabilities in behavioral patterns and Cs-137 surface-activity levels. Five years after the initial contamination, the 95th percentiles of indoor workers and pensioners in 53 of the 59 municipalities were found to receive annual effective doses of below 1 mSv/y (0.026-0.73 mSv/y). However, for outdoor workers in 25 municipalities, the annual doses were over 1 mSv/y (1.0-35 mSv/y). Therefore, the guidance value is effective for indoor workers and pensioners; to determine whether additional countermeasures for outdoor workers should be implemented, a detailed assessment that uses more realistic assumptions is required. PMID- 27400652 TI - Deep divergence and rapid evolutionary rates in gut-associated Acetobacteraceae of ants. AB - BACKGROUND: Symbiotic associations between gut microbiota and their animal hosts shape the evolutionary trajectories of both partners. The genomic consequences of these relationships are significantly influenced by a variety of factors, including niche localization, interaction potential, and symbiont transmission mode. In eusocial insect hosts, socially transmitted gut microbiota may represent an intermediate point between free living or environmentally acquired bacteria and those with strict host association and maternal transmission. RESULTS: We characterized the bacterial communities associated with an abundant ant species, Camponotus chromaiodes. While many bacteria had sporadic distributions, some taxa were abundant and persistent within and across ant colonies. Specially, two Acetobacteraceae operational taxonomic units (OTUs; referred to as AAB1 and AAB2) were abundant and widespread across host samples. Dissection experiments confirmed that AAB1 and AAB2 occur in C. chromaiodes gut tracts. We explored the distribution and evolution of these Acetobacteraceae OTUs in more depth. We found that Camponotus hosts representing different species and geographical regions possess close relatives of the Acetobacteraceae OTUs detected in C. chromaiodes. Phylogenetic analysis revealed that AAB1 and AAB2 join other ant associates in a monophyletic clade. This clade consists of Acetobacteraceae from three ant tribes, including a third, basal lineage associated with Attine ants. This ant specific AAB clade exhibits a significant acceleration of substitution rates at the 16S rDNA gene and elevated AT content. Substitutions along 16S rRNA in AAB1 and AAB2 result in ~10 % reduction in the predicted rRNA stability. CONCLUSIONS: Combined, these patterns in Camponotus-associated Acetobacteraceae resemble those found in cospeciating gut associates that are both socially and maternally transmitted. These associates may represent an intermediate point along an evolutionary trajectory manifest most extremely in symbionts with strict maternal transmission. Collectively, these results suggest that Acetobacteraceae may be a frequent and persistent gut associate in Camponotus species and perhaps other ant groups, and that its evolution is strongly impacted by this host association. PMID- 27400654 TI - Radiological and material characterization of high volume fly ash concrete. AB - The main goal of research presented in this paper was the material and radiological characterization of high volume fly ash concrete (HVFAC) in terms of determination of natural radionuclide content and radon emanation and exhalation coefficients. All concrete samples were made with a fly ash content between 50% and 70% of the total amount of cementitious materials from one coal burning power plant in Serbia. Physical (fresh and hardened concrete density) and mechanical properties (compressive strength, splitting tensile strength and modulus of elasticity) of concrete were tested. The radionuclide content (226Ra, 232Th and 40K) and radon massic exhalation of HVFAC samples were determined using gamma spectrometry. Determination of massic exhalation rates of HVFAC and its components using radon accumulation chamber techniques combined with a radon monitor was performed. The results show a beneficial effect of pozzolanic activity since the increase in fly ash content resulted in an increase in compressive strength of HVFAC by approximately 20% for the same mass of cement used in the mixtures. On the basis of the obtained radionuclide content of concrete components the I -indices of different HVFAC samples were calculated and compared with measured values (0.27-0.32), which were significantly below the recommended 1.0 index value. The prediction was relatively close to the measured values as the ratio between the calculated and measured I-index ranged between 0.89 and 1.14. Collected results of mechanical and radiological properties and performed calculations clearly prove that all 10 designed concretes with a certain type of fly ash are suitable for structural and non-structural applications both from a material and radiological point of view. PMID- 27400655 TI - H4R activation utilizes distinct signaling pathways for the production of RANTES and IL-13 in human mast cells. AB - CONTEXT: The histamine H4 receptor functionally expressed on human mast cells and their signaling pathways for the production of IL-13 and RANTES have never been analyzed side by side in a directly comparable manner. OBJECTIVE: Therefore, the aim of the study was to investigate signaling transduction pathways of H4R via ERK1/2, Akt and NFkappaB leading to the induction of inflammatory cytokine expression. MATERIALS AND METHODS: In the present study, HMC-1 cells and CBMCs were pretreated individually with H4R antagonist JNJ7777120, H1R antagonist mepyramine and signaling molecule inhibitors PD 98059, LY294002, Bay 117082 followed by stimulation was done with or without histamine or 4-MH. Furthermore, the siRNA mediated H4R gene silencing effects are studied at the H4R protein expression level and also signal transduction level. RESULTS: We found that the pretreatment with JNJ7777120 and H4R gene silencing decreased histamine, 4-MH induced phosphorylation of ERK1/2, Akt and NFkappaB-p65. Moreover, PD 98059, LY294002 and Bay 117082, which respectively inhibited the histamine and 4 methylhistamine induced phosphorylation of ERK1/2, Akt and NFkappaB-p65 respectively. We also found that the activation of H4R caused the release of IL 13 and RANTES on human mast cells. The MEK inhibitor PD98059 blocked H4R mediated RANTES/CCL5 production by 20.33 pg/ml and inhibited IL-13 generation by 95.71 pg/ml. In contrast, PI3 kinase inhibitor LY294002 had no effect on 4-MH induced RANTES/CCL5 production but blocked IL-13 generation by 117.58 pg/ml. DISCUSSION AND CONCLUSION: These data demonstrate that the H4R activates divergent signaling pathways to induce cytokine and chemokine production in human mast cells. PMID- 27400656 TI - Arteriovenous Fistula: The Backstory of the Birth of Cardiovascular Surgery. AB - The foundation for the celebrated operation on patent ductus arteriosus (PDA) in 1938 was the work on arteriovenous fistula (AVF) during the preceding half century. Galen and Osler wrote about it, and AVF was a major interest of leading surgeons of the late 19th and early 20th centuries, such as William Halsted, Rudolph Matas, Mont Reid, and Emile Holman. Nearly all AVFs of the era developed because of penetrating injury to major vessels. Survivors suffered gradual debilitation and faced death from gangrene or rupture. Development of an operation with a reasonable chance for success came only after the development of the cornerstones of modern surgery: suture, needles, anesthesia, and antiseptic and aseptic surgery. The only durable solution was quadruple ligation, ligation of both the vein and artery above and below the site of the fistula, and a technically demanding operation that risked ischemia and gangrene. Techniques pioneered by Alexis Carrel and Bernard Bertheim allowed strategies of early vascular reconstruction that reestablished normal circulation. Seeing patients with AVF with heart failure, Halsted recognized PDA as a naturally occurring AVF. Other surgeons proposed that ligation of PDA would be lifesaving. The struggles to understand and devise operative strategies to deal with AVF were the first steps toward the spectacular advances in cardiovascular surgery that followed. PMID- 27400657 TI - Implementation of immunochemical faecal occult blood test in general practice: a study protocol using a cluster-randomised stepped-wedge design. AB - BACKGROUND: Colorectal cancer is a common malignancy and a leading cause of cancer-related death. Half of patients with colorectal cancer initially present with non-specific or vague symptoms. In the need for a safe low-cost test, the immunochemical faecal occult blood test (iFOBT) may be part of the evaluation of such patients in primary care. Currently, Danish general practitioners have limited access to this test. The aim of this article is to describe a study that will assess the uptake and clinical use of iFOBT in general practice. Furthermore, it will investigate the diagnostic value and the clinical implications of using iFOBT in general practice on patients presenting with non alarm symptoms of colorectal cancer. METHODS/DESIGN: The study uses a cluster randomised stepped-wedge design and is conducted in the Central Denmark Region among 836 GPs in 381 general practices. The municipalities of the Region and their appertaining general practitioners will be included sequentially in the study during the first 7 months of the 1-year study period. The following intervention has been developed for the study: a mandatory intervention providing all general practitioners with a starting package of 10 iFOBTs, a clinical instruction on iFOBT use in general practice and online information material from the date of inclusion, and an optional intervention consisting of a continuous medical education on colorectal cancer diagnostics and use of iFOBT. DISCUSSION: This study is among the first and largest trials to investigate the diagnostic use and the clinical value of iFOBT on patients presenting with non-alarm symptoms of colorectal cancer. The findings will be of national and international importance for the future planning of colorectal cancer diagnostics, particularly for 'low-risk-but-not-no-risk' patients with non-alarm symptoms of colorectal cancer. TRIAL REGISTRATION: A Trial of the Implementation of iFOBT in General Practice NCT02308384 . Date of registration: 26 November 2014. PMID- 27400658 TI - Health status and access to health services of female prisoners in Greece: a cross-sectional survey. AB - BACKGROUND: Self-reported health status of prisoners' population and access to health services during incarceration have not been adequately explored in Greece. The purpose of this study was to assess female prisoners' health status and access to healthcare in the Attica detention center "Korydallos". METHODS: A cross-sectional survey was carried out in 2014. A semi-structured questionnaire was developed, including questions on the prisoners' socio-demographic characteristics, self-reported health status before and after incarceration, access to and quality of the provided health services. Inmates who were in solitary confinement, suffered from serious psychiatric problems, or were unable to understand the Greek language were excluded from the study. Data were collected via personal interviews and information received was anonymized. Descriptive statistics and bivariate analyses were used. The difference between self-reported general health status prior to and during detention was analyzed by Wilcoxon test, while the relationship between health status and access to healthcare was explored with coefficient Spearman's rho. Statistical significance was set at p <= 0.05 level and statistical analysis was performed using the software SPSS 19. RESULTS: Of the 135 prisoners, 101 participated in the study. 60.4 % mentioned a moderate or poor health status, while the respective percentage before detention was 32.7 %. Health status deterioration and poor mental health were reported by more than half of the respondents. Additionally, the vast majority expressed raised feelings such as sadness, anxiety or discomfort which affected negatively their everyday life while in prison. Regarding risk factors during imprisonment; tobacco consumption has increased by 16.6 % and 7.9 % of the sample admitted having used drugs. Moreover, the access to and the quality of provided health services in prison were described as poor/ very poor by 46.5 % and 49.5 %, respectively. A significant correlation between the access to and the quality of health care services and health status was observed. CONCLUSION: Healthcare provision at the "Korydallos" prison is not satisfying since the access to as well as the quality of healthcare are not adequate. Imprisonment leads to deterioration of self-reported health status. Our findings should constitute a starting point for further research in order to introduce more effective interventions aiming at meeting prisoners' health needs. PMID- 27400659 TI - The association between social capital and loneliness in different age groups: a population-based study in Western Finland. AB - BACKGROUND: Previous studies of loneliness have largely focused on establishing risk factors in specific age groups such as in later life or in young people. Researchers have paid less attention to the link between social capital and loneliness across different age groups. The aim of this study was to examine the association between social capital and experienced loneliness in different age groups in a Finnish setting. METHODS: The data originates from a population-based cross-sectional survey conducted among 4618 people aged 15-80 in Western Finland in 2011. The response rate was 46.2 %. The association between social capital, measured by frequency of social contacts, participation in organisational activities, trust and sense of belonging to the neighbourhood and loneliness was tested by logistic regression analyses stratified by four age groups. RESULTS: Frequent loneliness (defined as experienced often or sometimes) was higher among younger people (39.5 %) compared to older people (27.3 %). Low levels of trust were linked to loneliness in all four age groups. The association between other aspects of social capital and loneliness varied across age groups. CONCLUSIONS: Frequent loneliness is common among the general adult population and could be seen as a public health issue. Our findings imply that low social capital, especially in terms of low trust, may be a risk factor for loneliness. However, further research is needed to assess the influence of poor health and reverse causality as explanations for the findings. PMID- 27400660 TI - Do Consultation Psychiatrists, Forensic Psychiatrists, Psychiatry Trainees, and Health Care Lawyers Differ in Opinion on Gray Area Decision-Making Capacity Cases? A Vignette-Based Survey. AB - BACKGROUND: Previous research in the area of medical decision-making capacity has demonstrated relatively poor agreement between experienced evaluators in "gray area" cases. We performed a survey to determine the level of agreement about gray area decision-making capacity case scenarios within and between individuals of different professional backgrounds. METHOD: Participants received a survey consisting of 3 complicated decision-making capacity vignettes with an accompanying "yes/no" question regarding capacity and a certainty scale for each vignette. Participants were identified from mailing lists of professional organizations and local hospitals. We received responses from psychiatry trainees, consultation-liaison psychiatrists, forensic psychiatrists, and lawyers with experience in health care law. Results were analyzed using SPSS. RESULTS: Across the 3 vignettes, the percentage agreeing that the individual described had capacity to refuse medical treatment ranged between 35% and 40% for trainees, 33% and 67% for consult psychiatrists, 41% and 76% for forensic psychiatrists, and 40% and 83% for health care lawyers. Only question 2 reached significance between group differences (Pearson chi(2) = 11.473, p < 0.01). Across vignettes, trainees were less likely to consider patients to have capacity for decision-making than were forensic psychiatrists and lawyers. CONCLUSIONS: As found in previous research, agreement among experienced evaluators appears generally low in gray area capacity cases. It is noteworthy that individuals of different professional backgrounds at times offer divergent between-group opinions on capacity. PMID- 27400661 TI - A test of the core process account of psychopathology in a heterogenous clinical sample of anxiety and depression: A case of the blind men and the elephant? AB - Many cognitive and behavioral processes, such as selective attention to threat, self-focused attention, safety-seeking behaviors, worry and thought suppression, have their foundations in research on anxiety disorders. Yet, they are now known to be transdiagnostic, i.e. shared across a wide range of psychological disorders. A more pertinent clinical and theoretical question is whether these processes are themselves distinct, or whether they reflect a shared 'core' process that maintains psychopathology. The current study utilized a treatment seeking clinical adult sample of 313 individuals with a range of anxiety disorders and/or depression who had completed self-report measures of widely ranging processes: affect control, rumination, worry, escape/avoidance, and safety-seeking behaviors. We found that only the first factor extracted from a principal components analysis of the items of these measures was associated with symptoms of anxiety and depression. Our findings supported the 'core process' account that had its origins in the field of anxiety disorders, and we discuss the implications for theory, clinical practice and future research across psychological disorders. PMID- 27400662 TI - Characteristics of ganglion cells in pituitary gangliocytomas. AB - The occurrence of ganglion cells in the sella turcica, in association or not with a pituitary adenoma, has been rarely reported. Various names have been employed for this rare entity, gangliocytoma being frequently used and recommended by WHO classification. Expression of cytokeratin in these ganglion cells has been previously occasionally reported, a very intriguing observation raising questions on the possible nature and derivation of these cells. We describe the pathological findings in three cases of growth hormone-producing adenomas, all sparsely granulated, showing the presence of a ganglion cell population admixed with an adenomatous component. A review of the literature is also provided. PMID- 27400663 TI - Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer. AB - To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR. PMID- 27400665 TI - Prostate cancer: Radiotherapy might improve survival, even in the oldest men. PMID- 27400664 TI - Thrombosis of pancreatic arteriovenous malformation induced by diagnostic angiography: case report. AB - BACKGROUND: We report on a case of pancreatic arteriovenous malformation (PAVM) that obliterated shortly after diagnostic angiography (DSA). PAVM is a rare anomaly that presents with upper abdominal pain, signs of acute pancreatitis and massive gastrointestinal bleeding. The management of PAVM is rather complex, with complete treatment usually accomplished only by a total extirpation of the affected organ or at least its involved portion. DSA prior to treatment decisions is helpful for characterizing symptomatic PAVM, since it can clearly depict the related vascular networks. In addition, interventional therapy can be performed immediately after diagnosis. CASE PRESENTATION: A 39-old male was admitted due to recurring upper abdominal pain that lasted several weeks. Initial examination revealed the absence of fever or jaundice, and the laboratory tests, including that for pancreatic enzymes, were unremarkable. An abdominal ultrasound (US) showed morphological and Doppler anomalies in the pancreas that were consistent with a vascular formation. A subsequent DSA depicted a medium-sized nidus, receiving blood supply from multiple origins but with no dominant artery. Coil embolization was not possible due to the small caliber of the feeding vessels. In addition, sclerotherapy was not performed so as to avoid an unnecessary wash out to the non-targeted duodenum. Consequently, the patient received no specific treatment for his symptomatic PAVM. A large increase in pancreatic enzymes was noticed shortly after the DSA procedure. Imaging follow-up by means of CT and MRI showed small amounts of peripancreatic fluid along with a limited area of intra parenchymal necrosis, indicating necrotizing pancreatitis. In the post angiography follow-up the patient was hemodynamically stable the entire time and was treated conservatively. The symptoms of pancreatitis improved over a few days, and the laboratory findings returned to normal ranges. Long-term follow-up by way of a contrast-enhanced CT revealed no recanalization of the thrombosed PAVM. CONCLUSION: The factors associated with the obliteration of PAVM during or after DSA are poorly understood. In our case it may be attributed to the low flow dynamics of PAVM, as well as to the local administration of a contrast agent. Asymptomatic PAVM, as diagnosed with non-invasive imaging techniques, should not be evaluated with DSA due to the potential risk of severe complications, such as acute pancreatitis. PMID- 27400666 TI - Kidney cancer: Quality-of-life outcomes in patients with small renal masses. PMID- 27400667 TI - Prostate cancer: Why the prostate arm of the PLCO trial failed and what it has taught us. PMID- 27400668 TI - Prostate cancer: Tumour genomes are highly plastic. PMID- 27400669 TI - Biological and molecular characterization of a rare case of cutaneous Richter syndrome. AB - Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia in a high-grade lymphoma usually presenting nodal and bone marrow involvement. Richter syndrome can be localized at extranodal sites including the gastrointestinal tract, lungs, and skin. Cutaneous RS is an extremely rare disease apparently showing a less aggressive course than common presentations. While nodal RS has been extensively investigated in literature, pathogenesis and prognosis of cutaneous RS are still partially unknown, even if a role of Epstein-Barr virus infection and p53 disruption has been suggested. Herein, we characterized the histopathological, immunohistochemical features and cytogenetics and molecular alterations of a case of cutaneous RS developed after 8 years chronic lymphocytic leukemia history. Moreover, we reviewed the literature reports concerning cutaneous RS and made a focus on biological patterns and prognostic implications. PMID- 27400670 TI - Toward quantifying the abuse liability of ultraviolet tanning: A behavioral economic approach to tanning addiction. AB - Many adults engage in ultraviolet indoor tanning despite evidence of its association with skin cancer. The constellation of behaviors associated with ultraviolet indoor tanning is analogous to that in other behavioral addictions. Despite a growing literature on ultraviolet indoor tanning as an addiction, there remains no consensus on how to identify ultraviolet indoor tanning addictive tendencies. The purpose of the present study was to translate a behavioral economic task more commonly used in substance abuse to quantify the "abuse liability" of ultraviolet indoor tanning, establish construct validity, and determine convergent validity with the most commonly used diagnostic tools for ultraviolet indoor tanning addiction (i.e., mCAGE and mDSM-IV-TR). We conducted a between-groups study using a novel hypothetical Tanning Purchase Task to quantify intensity and elasticity of ultraviolet indoor tanning demand and permit statistical comparisons with the mCAGE and mDSM-IV-TR. Results suggest that behavioral economic demand is related to ultraviolet indoor tanning addiction status and adequately discriminates between potential addicted individuals from nonaddicted individuals. Moreover, we provide evidence that the Tanning Purchase Task renders behavioral economic indicators that are relevant to public health research. The present findings are limited to two ultraviolet indoor tanning addiction tools and a relatively small sample of high-risk ultraviolet indoor tanning users; however, these pilot data demonstrate the potential for behavioral economic assessment tools as diagnostic and research aids in ultraviolet indoor tanning addiction studies. PMID- 27400671 TI - What is the evidence for metabolic surgery for type 2 diabetes? A critical perspective. AB - Bariatric surgery has emerged as a highly effective treatment not only for obesity, but also for type 2 diabetes (T2D). A meta-analysis has reported the complete resolution of T2D in 78.1% of cases of morbidly obese patients after bariatric surgery. Such extraordinary results obtained in diabetic patients with body mass index (BMI) scores>35kg/m2 have led investigators to question whether similar results might be achieved in patients with BMIs<35kg/m2. Preliminary studies suggest that metabolic surgery is safe and effective in patients with T2D and a BMI<35kg/m2, whereas other studies report that metabolic surgery is less effective for promoting T2D remission in these patients. Thus, the results are discordant. Long-term studies would be useful for determining the safety, efficacy and cost-effectiveness of metabolic surgery for this population with T2D. In 2015, it is probably premature to say that metabolic surgery is an accepted treatment option for T2D patients with BMIs<35kg/m2. PMID- 27400672 TI - Ex vivo model exhibits protective effects of sesamin against destruction of cartilage induced with a combination of tumor necrosis factor-alpha and oncostatin M. AB - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis. TNF-alpha and OSM are pro-inflammatory cytokines that play a key role in RA progression. Thus, reducing the effects of both cytokines is practical in order to relieve the progression of the disease. This current study is interested in sesamin, an active compound in sesame seeds. Sesamin has been shown to be a chondroprotective agent in osteoarthritis models. Here, we have evaluated a porcine cartilage explant as a cartilage degradation model related to RA induced by TNF-alpha and/or OSM in order to investigate the effects of sesamin on TNF-alpha and OSM in the cartilage degradation model. METHODS: A porcine cartilage explant was induced with a combination of TNF-alpha and OSM (test group) or IL-1beta and OSM (control group) followed by a co treatment of sesamin over a long-term period (35 days). After which, the tested explants were analyzed for indications of both the remaining and the degradation aspects using glycosaminoglycan and collagen as an indicator. RESULTS: The combination of TNF-alpha and OSM promoted cartilage degradation more than either TNF-alpha or OSM alone and was comparable with the combination of IL-1beta and OSM. Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model. CONCLUSIONS: Sesamin might be a promising agent as an alternative treatment for RA patients. Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA. The model could be used to test for the prevention of cartilage degradation in other biological agents induced with TNF-alpha and OSM as well. PMID- 27400673 TI - Enhanced stiffness of silk-like fibers by loop formation in the corona leads to stronger gels. AB - We study the self-assembly of protein polymers consisting of a silk-like block flanked by two hydrophilic blocks, with a cysteine residue attached to the C terminal end. The silk blocks self-assemble to form fibers while the hydrophilic blocks form a stabilizing corona. Entanglement of the fibers leads to the formation of hydrogels. Under oxidizing conditions the cysteine residues form disulfide bridges, effectively connecting two corona chains at their ends to form a loop. We find that this leads to a significant increase in the elastic modulus of the gels. Using atomic force microscopy, we show that this stiffening is due to an increase of the persistence length of the fibers. Self-consistent-field calculations indicate a slight decrease of the lateral pressure in the corona upon loop formation. We argue that this small decrease in the repulsive interactions affects the stacking of the silk-like blocks in the core, resulting in a more rigid fiber. PMID- 27400674 TI - Urbanization is associated with increased asthma morbidity and mortality in Brazil. AB - INTRODUCTION: Previous cross-sectional studies could establish an association between prevalence of self-reported wheeze and urban-rural environment, but the impact of urbanization on meaningful outcomes of asthma for public health is not established yet. OBJECTIVES: Evaluate the effect of urbanization on asthma burden. METHODS: A time series study of 5,505 Brazilian municipalities. The unit of analysis was the municipality. Two time frames were evaluated: from 1999 to 2001 and from 2009 to 2011. Trends from the first to the second time frame were evaluated. Governmental databases were the source of information. Multivariate binary logistic regression models were used. RESULTS: In the age range from 5 to 24 years old, municipalities with increase in the proportion of individuals living in urban area had lower odds to reduce hospital admission rate from asthma (OR: .93) and lower odds to reduce death rate from asthma (OR: .88). In the age range from 25 to 39 years old, municipalities with increase in the proportion of individuals living in urban area had lower odds to reduce hospital admission rate from asthma (OR: .93) and lower odds to reduce death rate from asthma (OR: .82). Municipalities that increased access to physicians and that supplied inhaled corticosteroids free of charge for asthma since year 2003 had increased odds to reduce hospital admission and death rates from asthma. CONCLUSIONS: Increase in urban population was associated with lower odds to reduce hospital admission and death rates from asthma in children and young adults living in a transition society. PMID- 27400675 TI - Subtraction of subcutaneous fat to improve the prediction of visceral adiposity: exploring a new anthropometric track in overweight and obese youth. AB - BACKGROUND: The efficiency of traditional anthropometric measurements such as body mass index (BMI) or waist circumference (Waist C) used to replace biomedical imaging for assessing visceral adipose tissue (VAT) is still highly controversial in youth. HYPOTHESIS AND OBJECTIVES: We evaluated the most accurate model predicting VAT in overweight/obese youth, using various anthropometric measurements and their correlation with different body fat compartments, especially by testing, for the first time in youth, the hypothesis that subtracting the anthropometric measurement the most highly correlated with subcutaneous abdominal adipose tissue (SAAT) and less correlated possible with VAT from an anthropometric abdominal measurement highly correlated with visceral and total abdominal adipose tissue (TAAT), predicts VAT with higher accuracy. SUBJECTS AND METHODS: VAT and SAAT data resulted from magnetic resonance imaging (MRI) analysis performed on 181 boys and girls (7-17 y) from Diabetes & Endocrinology Care Paediatrics Clinic in Luxembourg. Height, weight, abdominal diameters, waist, hip, and thigh circumferences were measured with a view to developing the anthropometric VAT predictive algorithms. RESULTS: In girls, subtracting proximal thigh circumference (Proximal Thigh C), the most closely correlated anthropometric measurement with SAAT, from Waist C, the most closely correlated anthropometric measurement with VAT was instrumental in improving VAT prediction, in comparison with the most accurate single VAT anthropometric surrogate. [Formula: see text] Residual analysis showed a negligible estimation error (5 cm2 ). In boys, Waist C was the best VAT predictor. CONCLUSIONS: Subtraction of abdominal subcutaneous fat is important to predict VAT in overweight/obese girls. PMID- 27400676 TI - Structural elucidation and NMR spectral assignments of paraconfuranones I-M from the insect-associated fungus Paraconiothyrium brasiliense. PMID- 27400677 TI - Structural changes in the inner ear over time studied in the experimentally deafened guinea pig. AB - Today a cochlear implant (CI) may significantly restore auditory function, even for people with a profound hearing loss. Because the efficacy of a CI is believed to depend mainly on the remaining population of spiral ganglion neurons (SGNs), it is important to understand the timeline of the degenerative process of the auditory neurons following deafness. Guinea pigs were transtympanically deafened with neomycin, verified by recording auditory brainstem responses (ABRs), and then sacrificed at different time points. Loss of SGNs as well as changes in cell body and nuclear volume were estimated. To study the effect of delayed treatment, a group of animals that had been deaf for 12 weeks was implanted with a stimulus electrode mimicking a CI, after which they received a 4-week treatment with glial cell-derived neurotrophic factor (GDNF). The electrical responsiveness of the SGNs was measured by recording electrically evoked ABRs. There was a rapid degeneration during the first 7 weeks, shown as a significant reduction of the SGN population. The degenerative process then slowed, and there was no difference in the amount of remaining neurons between weeks 7 and 18. (c) 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID- 27400678 TI - Innate lymphoid cells in normal and disease: An introductory overview. AB - Innate lymphoid cells (ILC) represent a novel group of lymphocytes that, different from T and B-lymphocytes lack recombinant activating genes (RAG-1 or RAG-2) and thus do not express rearranged antigen-specific receptors. Members of this family, i.e. NK cells, have been known since long time, while the other ILCs have been discovered only in recent years, possibly because of their predominant localization in tissues, primarily in mucosal tissues, skin and mucosa-associated lymphoid organs. ILC have been grouped in three major subsets on the basis of their phenotypic and functional features as well as of their dependency on given transcription factors (TF). Briefly, ILC-1 are dependent on T-bet TF and produce interferon (IFN)-gamma. Group 2 ILC (ILC2) express GATA-3 TF and produce IL-5, IL 4 and IL-13 (Type 2) cytokines while group 3 ILC (ILC3) express RORgammat TF and produce IL-17 and IL-22. ILC provide early defenses against pathogens and intervene in the repair of damaged tissues. ILC activation is mediated by cytokines (specifically acting on different ILC groups) and/or by activating receptors that are, at least in part, the same that had been previously identified in NK cells [1]. PMID- 27400679 TI - Porous Nickel-Iron Selenide Nanosheets as Highly Efficient Electrocatalysts for Oxygen Evolution Reaction. AB - Exploring non-noble and high-efficiency electrocatalysts is critical to large scale industrial applications of electrochemical water splitting. Currently, nickel-based selenide materials are promising candidates for oxygen evolution reaction due to their low cost and excellent performance. In this work, we report the porous nickel-iron bimetallic selenide nanosheets ((Ni0.75Fe0.25)Se2) on carbon fiber cloth (CFC) by selenization of the ultrathin NiFe-based nanosheet precursor. The as-prepared three-dimensional oxygen evolution electrode exhibits a small overpotential of 255 mV at 35 mA cm(-2) and a low Tafel slope of 47.2 mV dec(-1) and keeps high stability during a 28 h measurement in alkaline solution. The outstanding catalytic performance and strong durability, in comparison to the advanced non-noble metal catalysts, are derived from the porous nanostructure fabrication, Fe incorporation, and selenization, which result in fast charge transportation and large electrochemically active surface area and enhance the release of oxygen bubbles from the electrode surface. PMID- 27400680 TI - Disability and recovery in schizophrenia: a systematic review of cognitive behavioral therapy interventions. AB - BACKGROUND: Schizophrenia is a disabling disease that impacts all major life areas. There is a growing need for meeting the challenge of disability from a perspective that extends symptomatic reduction. Therefore, this study aimed to systematically review the extent to which traditional and "third wave" cognitive behavioral (CBT) interventions address the whole scope of disabilities experienced by people with lived experience of schizophrenia using the WHO's International Classification of Functioning, Disability and Health (ICF) as a frame of reference. It also explores if current CBT interventions focus on recovery and what is their impact on disability domains. METHODS: Medline and PsycINFO databases were searched for studies published in English between January 2009 and December 2015. Abstracts and full papers were screened against pre defined selection criteria by two reviewers. Methodological quality of included studies was assessed by two independent raters using the Effective Public Health Practice Project Quality assessment tool for quantitative studies (EPHPP) guidelines. RESULTS: A total of 50 studies were included, 35 studies evaluating traditional CBT interventions and 15 evaluating "third wave" approaches. Overall, traditional CBT interventions addressed more disability domains than "third wave" approaches and mostly focused on mental functions reflecting schizophrenia psychopathology. Seven studies met the inclusion criteria of recovery-oriented interventions. The majority of studies evaluating these interventions had however a high risk of bias, therefore evidence on their effectiveness is inconclusive. CONCLUSIONS: Traditional CBT interventions address more disability domains than "third wave" therapies, however both approaches focus mostly on mental functions that reflect schizophrenia psychopathology. There are also few interventions that focus on recovery. These results indicate that CBT interventions going beyond symptom reduction are still needed. Recovery-focused CBT interventions seem to be a promising treatment approach as they target disability from a broader perspective including activity and participation domains. Although their effectiveness is inconclusive, they reflect users' views of recovery and trends towards improvement of mood, negative symptoms and functioning are shown. PMID- 27400681 TI - GFRalpha2 prompts cell growth and chemoresistance through down-regulating tumor suppressor gene PTEN via Mir-17-5p in pancreatic cancer. AB - Nerve growth factors and their receptors have received an increasing attention in certain cancers since they play an important role in regulating tumorigenesis, biological process and metastasis. Here we aimed at characterizing a new function of one of the subtypes of growth factor receptors (GFR), GFRalpha2, in pancreatic cancer. In this study, we showed that GFRalpha2 was up-regulated in pancreatic adenocarcinoma and was positively correlated with tumor size and perineural invasion, which indicated that it may be associated with cell growth and apoptosis. Mechanically, we discovered that high GFRalpha2 expression level leads to PTEN inactivation via enhancing Mir-17-5p level. PMID- 27400682 TI - Quality management in clinical application of mass spectrometry measurement systems. AB - Thanks to highly specific analyte detection and potentially complete compensation for matrix variables based on the principle of stable isotope derivative internal standardisation, mass spectrometry methods allow the development of diagnostic tests of outstanding analytical quality. However, these features per se do not guarantee reliability of tests. A wide range of factors can introduce analytical errors and inaccuracy due to the extreme complexity of the methods involved. Furthermore, it can be expected that the application patterns of MS methods in diagnostic laboratories will change substantially during the coming years - with presumably less specialised laboratories implementing mass spectrometry. Introduction of highly automated test solutions by manufacturers will require some trade-off between operation convenience, sample throughput and analytical performance. Structured and careful quality and risk management is therefore crucial to translate the analytical power of mass spectrometry into actionable and reliable results for individual patients' care and to maintain the degree of reliability that is expected from MS methods in clinical pathology. This reflection review discusses whether particular quality assurance tools have to be applied for MS-based diagnostic tests and whether these tools are different from those applied for optical- and affinity-based standard tests. Both pre implementation strategies and surveillance of assays with assessment of metadata in routine testing are addressed. The release of the CLSI guideline C62-A in 2014 was a substantial achievement in this context because it addresses a wide spectrum of relevant issues in quality assurance of mass spectrometry-based clinical tests. However, the translation of this best practice document into individual laboratory settings is likely to be heterogeneous. PMID- 27400683 TI - Validation List No. 169. List of new names and new combinations previously effectively, but not validly, published. PMID- 27400684 TI - Effects of selenite on chlorophyll fluorescence, starch content and fatty acid in the duckweed Landoltia punctata. AB - Developing a Se-enriched feed for animal has become a considerable effort. In this study, Landoltia punctata 7449 was grown over a 12 day period under concentrations of selenite (Na2SeO3) from 0 to 80 MUmol L(-1). The growth rate, the chlorophyll fluorescence, the starch content and fatty acid were measured. Se at low concentrations of <=20 MUmol L(-1) had positive effects also on growth rate, fatty acid content and yield of the L. punctata. The appropriate Se treatment enhanced the activity of the photosynthetic system by increasing Fv, Fm, Fv/Fm and Fv/Fo and decreasing Fo. However, negative impact to the L. punctata was observed when the duckweed was exposed to high Se concentrations (>=40 MUmol L(-1)). Significant increases in starch content in the duckweed were observed after Se application. The present study suggests that the changes in growth rate, the photosynthetic system, the starch content and the fatty acid were closely associated with the application of Se. An increased Se concentration (0-20 MUmol L(-1)) in duckweed could positively induce photosynthesis, thereby increasing the yield of L. punctata and could be a resource for high nutritive quality Se-enrich feed. PMID- 27400685 TI - A penetrating atherosclerotic ulcer rupture in the ascending aorta with hemopericardium: a case report. AB - BACKGROUND: Acute aortic syndrome, including classic aortic dissection, intramural aortic hematoma, and penetrating atherosclerotic ulcer (PAU), is a term used to describe a group of conditions with similar clinical symptoms, but with different pathophysiological mechanisms. PAU is a lesion that penetrates the internal elastic lamina through the media. It is usually located in the descending aorta and rarely observed in the ascending aorta. CASE PRESENTATION: A 76-year-old man with a history of essential hypertension was brought to the emergency department (ED) because of a sudden-onset chest pain at rest. He had not been taking his medication as ordered. His vital signs in the ED were a blood pressure of 82/60 mmHg, heart rate of 158 beats per min, respiratory rate of 22 breaths per min, and a body temperature of 37.2 degrees C. An electrocardiogram did not show an ST segment elevation, and cardiac enzymes were within normal limits. No widening mediastinum was found on chest radiography, but a large pericardial effusion with an impending cardiac tamponade was revealed on echocardiography. The diagnosis of PAU rupture in the ascending aorta with hemopericardium was made with chest computed tomography. An emergent sternotomy and ascending aorta reconstruction were performed. A ruptured ulcerative plaque through the intima to the adventitia without flap dissection in the ascending aorta was confirmed. The patient was discharged 18 days after the operation. CONCLUSIONS: Although PAU in the ascending aorta is uncommon, it is commonly lethal when it ruptures. With the current advances in endovascular techniques and devices, endovascular repair of PAU in the ascending aorta is currently recommended only for high-risk patients unsuitable for open repair. However, we anticipate that endovascular repair may become feasible in patients with PAU in the ascending aorta in the future. PMID- 27400687 TI - Development of a protein-ligand-binding site prediction method based on interaction energy and sequence conservation. AB - We present a new method for predicting protein-ligand-binding sites based on protein three-dimensional structure and amino acid conservation. This method involves calculation of the van der Waals interaction energy between a protein and many probes placed on the protein surface and subsequent clustering of the probes with low interaction energies to identify the most energetically favorable locus. In addition, it uses amino acid conservation among homologous proteins. Ligand-binding sites were predicted by combining the interaction energy and the amino acid conservation score. The performance of our prediction method was evaluated using a non-redundant dataset of 348 ligand-bound and ligand-unbound protein structure pairs, constructed by filtering entries in a ligand-binding site structure database, LigASite. Ligand-bound structure prediction (bound prediction) indicated that 74.0 % of predicted ligand-binding sites overlapped with real ligand-binding sites by over 25 % of their volume. Ligand-unbound structure prediction (unbound prediction) indicated that 73.9 % of predicted ligand-binding residues overlapped with real ligand-binding residues. The amino acid conservation score improved the average prediction accuracy by 17.0 and 17.6 points for the bound and unbound predictions, respectively. These results demonstrate the effectiveness of the combined use of the interaction energy and amino acid conservation in the ligand-binding site prediction. PMID- 27400688 TI - Structural mapping of Kelch13 mutations associated with artemisinin resistance in malaria. AB - Mutations in Plasmodium falciparum gene kelch13 (pfkelch13) are strongly and causally associated with resistance to anti-malarial drug artemisinin, but their effects on PfKelch13 structure and function remain unclear. Utilizing the publicly available three-dimensional structure of PfKech13 (PDB ID: 4yy8), we find that most of the mutations in its propeller domain occur in two spatial clusters. Of these, one cluster is enriched in surface exposed residues which may drive PfKelch13-centered protein interactions, and the second cluster mostly contains residues which are buried and whose mutations may destabilize PfKelch13 structure. The most prevalent resistant mutations C580Y and Y493H are distal from the above two clusters. The C580Y mutation creates sterically unfavourable contacts while Y493H possibly alters the hydrophobic core of the propeller domain. These analyses will facilitate further experimental studies aimed at understanding how mutations in pfkelch13 lead to artemisinin resistance. PMID- 27400690 TI - Congenital heart disease units will close in Manchester, Leicester, and the Royal Brompton. PMID- 27400689 TI - Granisetron Transdermal System for Treatment of Symptoms of Gastroparesis: A Prescription Registry Study. AB - Background/Aims: Serotonin receptor (eg, 5-HT3) antagonists are used to treat nausea and vomiting from a variety of causes. Granisetron transdermal system (GTS) is an appealing delivery system for patients with gastroparesis. To assess if GTS improves nausea and vomiting and other gastroparesis symptoms in patients with gastroparesis. Methods: Patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTS. Symptoms of gastroparesis were assessed using a modified Gastroparesis Cardinal Symptom Index (GCSI). Following 2 weeks of treatment, patients were asked to assess their symptoms and indicate their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS) reporting if symptoms of nausea and vomiting improved on a scale: 0 = no change to +7 = completely better. Results: Fifty-one patients received GTS by prescription: average age was 40 +/- 17 years, 44 female, 11 diabetics, 23 +/- 20% retention at 4 hours on gastric emptying scintigraphy. Thirty-nine of the 51 (76%) patients stated improvement with GTS. There was significant improvement in nausea and vomiting as assessed with CPGAS at 2 weeks (2.28 +/- 2.53; P < 0.05). Symptoms of nausea and vomiting significantly improved. Other symptoms including postprandial fullness, loss of appetite, upper abdominal pain, and early satiety improved. Side effects reported included redness at the site of the patch in 7 patients, pruritus in 5, and constipation in 5. Conclusions: GTS was moderately effective in reducing nausea and/or vomiting in 76% of gastroparesis patients. In addition to nausea and vomiting, symptoms of postprandial fullness, loss of appetite, upper abdominal pain, and early satiety also improved. PMID- 27400686 TI - From animal models to human disease: a genetic approach for personalized medicine in ALS. AB - Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases. PMID- 27400691 TI - A novel approach for the analysis of longitudinal profiles reveals delayed progression to type 1 diabetes in a subgroup of multiple-islet-autoantibody positive children. AB - AIMS/HYPOTHESIS: Progression to type 1 diabetes in children and adolescents is not uniform. Based on individual genetic background and environment, islet autoimmunity may develop at variable age, exhibit different autoantibody profiles and progress to clinical diabetes at variable rates. Here, we aimed to quantify the qualitative dynamics of sequential islet autoantibody profiles in order to identify longitudinal patterns that stratify progression rates to type 1 diabetes in multiple-autoantibody-positive children. METHODS: Qualitative changes in antibody status on follow-up and progression rate to diabetes were analysed in 88 children followed from birth in the prospective BABYDIAB study who developed multiple autoantibodies against insulin (IAA), GAD (GADA), insulinoma-associated antigen-2 (IA-2A) and/or zinc transporter 8 (ZnT8A). An algorithm was developed to define similarities in sequential autoantibody profiles and hierarchical clustering was performed to group children with similar profiles. RESULTS: We defined nine clusters that distinguished children with respect to their sequential profiles of IAA, GADA, IA-2A and ZnT8A. Progression from first autoantibody appearance to clinical diabetes between clusters ranged from 6% (95% CI [0, 16.4]) to 73% (28.4, 89.6) within 5 years. Delayed progression was observed in children who were positive for only two autoantibodies, and for a cluster of 12 children who developed three or four autoantibodies but were IAA negative in their last samples, nine of whom lost IAA positivity during follow up. Among all children who first seroconverted to IAA positivity and developed at least two other autoantibodies (n = 57), the 10 year risk of diabetes was 23% (0, 42.9) in those who became IAA-negative during follow-up compared with 76% (58.7, 85.6) in those who remained IAA-positive (p = 0.004). CONCLUSIONS/INTERPRETATION: The novel clustering approach provides a tool for stratification of islet autoantibody-positive individuals that has prognostic relevance, and new opportunities in elucidating disease mechanisms. Our data suggest that losing IAA reactivity is associated with delayed progression to type 1 diabetes in multiple islet-autoantibody-positive children. PMID- 27400693 TI - Residency Patient Safety Curricula and American Board of Psychiatry and Neurology Patient Safety Courses. PMID- 27400692 TI - Short-term outcomes and one surgeon's learning curve for thoracoscopic esophagectomy performed with the patient in the prone position. AB - PURPOSE: Thoracoscopic esophagectomy with the patient in the prone position (TEP) is now being performed as minimally invasive esophagectomy for esophageal cancer. This study examines the short-term outcomes and the learning curve associated with TEP. METHODS: One surgeon ("Surgeon A") performed TEP on 100 consecutive patients assigned to three periods based on treatment order. Each group consisted of 33 or 34 patients. The outcomes of the three groups were compared to define the influence of surgeon expertise. RESULTS: Outcomes improved as Surgeon A gained experience in performing this operation, as evidenced by reduced thoracic operative times between periods 1 and 2, and then between periods 2 and 3 (p = 0.0033 and p = 0.0326, respectively); an increased number of retrieved chest nodes between periods 1 and 2 (p = 0.0070); and a decline in recurrent laryngeal nerve (RLN) palsy between periods 2 and 3 (p = 0.0450). Period 2 was the pivotal period for each learning curve. CONCLUSIONS: An individual surgeon's learning curve over the course of 100 TEP procedures had three outcomes: a shortened operative time, a higher number of retrieved chest nodes, and a decreased rate of RLN palsy. Approximately 30-60 cases were needed to reach a plateau in the TEP procedure and a reduction in the morbidity rate. PMID- 27400694 TI - Biofilm on the tracheoesophageal voice prosthesis: considerations for oral decontamination. AB - The tracheoesophageal puncture (TEP) restores verbal communication after total laryngectomy using a one-way valved voice prosthesis (VP). Microbial colonization can shorten VP device life. Our aims were to investigate patterns of prosthetic and oral colonization, and record changes in VP device life after targeted decontamination. We conducted a retrospective review of TEP clinic patients who underwent microbial analysis of the VP between 01/2003 and 07/2013. Two subgroups were analyzed: (1) patients with microbial analysis of the VP and the mouth were analyzed to identify patterns of common contamination, and (2) patients who were prescribed targeted oral decontamination on the basis of the microbial analysis of the VP were analyzed to evaluate effects on device life. Among 42 patients, 3 patients had only fungal, 5 only bacterial, and 33 had polyspecies fungal and bacterial colonization. In the TEP-oral microflora subgroup (n = 15), 7 had common microorganisms in the mouth and on the VP. Among the decontamination subgroup (n = 23), 6 patients received broad spectrum rinse, 16 antifungal agents and 13 antibiotics, or a combination thereof. After targeted decontamination, the median device life of prostheses improved from 7.89 to 10.82 weeks (p = 0.260). The majority of patients with a suboptimal VP device life in this pilot had polyspecies bacterial and fungal colonization. VPs rarely had fungal contamination alone (3 %), and non-albicans fungal species were more common than expected. For these reasons, we are exploring the use of targeted decontamination regimens that were associated with 1.4-fold improvement in VP duration. PMID- 27400695 TI - A Triple Knockout (TKO) Proteomics Standard for Diagnosing Ion Interference in Isobaric Labeling Experiments. AB - Isobaric labeling is a powerful strategy for quantitative mass spectrometry-based proteomic investigations. A complication of such analyses has been the co isolation of multiple analytes of similar mass-to-charge resulting in the distortion of relative protein abundance measurements across samples. When properly implemented, synchronous precursor selection and triple-stage mass spectrometry (SPS-MS3) can reduce the occurrence of this phenomenon, referred to as ion interference. However, no diagnostic tool is available currently to rapidly and accurately assess ion interference. To address this need, we developed a multiplexed tandem mass tag (TMT)-based standard, termed the triple knockout (TKO). This standard is comprised of three yeast proteomes in triplicate, each from a strain deficient in a highly abundant protein (Met6, Pfk2, or Ura2). The relative abundance patterns of these proteins, which can be inferred from dozens of peptide measurements can demonstrate ion interference in peptide quantification. We expect no signal in channels where the protein is knocked out, permitting maximum sensitivity for measurements of ion interference against a null background. Here, we emphasize the need to investigate further ion interference-generated ratio distortion and promote the TKO standard as a tool to investigate such issues. Graphical Abstract ?. PMID- 27400697 TI - Medical boards often shield doctors guilty of sexual misconduct, investigation finds. PMID- 27400696 TI - Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas Phase Ion Structures and Ion Mobility Characterization. AB - Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions. Graphical Abstract ?. PMID- 27400699 TI - The (re)-introduction of semiotics into medical education: on the works of Thure von Uexkull. AB - Thure von Uexkull's reputation as a pioneer in biosemiotics and also in psychosomatic medicine is well documented. It is easy to see these disciplines reflected in his notable publications, both in English and in German. However, if one spares the time to filter through all of his articles, monographs, conference papers and editorials in English and in German, a notable gap arises in his English language publications: that of clinical education. This gap in the English language literature may seem unimportant in and of itself, but it speaks volumes when we consider the total absence of medical semiotics in the curriculum of medical schools in the English speaking world. This runs in stark contrast to the strong traditions of psychosomatic medicine in Germany, which Thure von Uexkull largely helped to instil. Do the works of Thure von Uexkull offer a possible step towards a resurrection of medical semiotics in clinical education? This chapter attempts to explore the lesser known German literature on clinical education that Thure von Uexkull produced, and explore the role semiotics can play in Medical Education in the English speaking world. While also seeking to contrast this literature with other existing approaches in British and American medical schools who have attempted to reintroduce medical humanities and reflexive thinking into clinical education. PMID- 27400698 TI - Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial. AB - After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials. PMID- 27400700 TI - Single-energy metal artifact reduction for helical computed tomography of the pelvis in patients with metal hip prostheses. AB - PURPOSE: To compare the quality of helical computed tomography (CT) images of the pelvis in patients with metal hip prostheses reconstructed using adaptive iterative dose reduction (AIDR) and AIDR with single-energy metal artifact reduction (SEMAR-A). MATERIALS AND METHODS: This retrospective study included 28 patients (mean age, 64.6 +/- 11.4 years; 6 men and 22 women). CT images were reconstructed using AIDR and SEMAR-A. Two radiologists evaluated the extent of metal artifacts and the depiction of structures in the pelvic region and looked for mass lesions. A radiologist placed a region of interest within the bladder and recorded CT attenuation. RESULTS: The metal artifacts were significantly reduced in SEMAR-A as compared to AIDR (p < 0.0001). The depictions of the bladder, ureter, prostate/uterus, rectum, and pelvic sidewall were significantly better with SEMAR-A than with AIDR (p < 0.02). All lesions were diagnosed with SEMAR-A, while some were not diagnosed with AIDR. The median and interquartile range (in parentheses) of CT attenuation within the bladder for AIDR were -34.0 ( 46.6 to -15.0) Hounsfield units (HU) and were more variable than those seen for SEMAR-A [5.4 (-1.3 to 11.1)] HU (p = 0.033). CONCLUSION: In comparison with AIDR, SEMAR-A provided pelvic CT images of significantly better quality for patients with metal hip prostheses. PMID- 27400701 TI - The effect of a resilience improvement program for adolescents with complex congenital heart disease. AB - BACKGROUND: Adolescents with congenital heart disease need to increase their resilience in the face of challenges in order to preserve their health and quality of life. AIMS: This study aimed to develop a resilience improvement program for adolescents with congenital heart disease and also to evaluate any change in resilience and quality of life as a measure of the effectiveness of the resilience improvement programs. METHODS: A nonequivalent control group pretest posttest study was designed. Twenty-five adolescents who attended the first resilience improvement program were included in the experimental group, and 31 adolescents who took part in the second program were placed in the control group. Adolescents with congenital heart disease completed a self-report questionnaire on three separate occasions: the pretest, the first posttest and the second posttest. The self-report questionnaire included general characteristics and instruments to measure resilience and quality of life. For the longitudinal analysis, generalized estimating equations were used to evaluate the difference in the estimated average trajectories of resilience and quality of life changes. RESULTS: Independent predictors of resilience improvement in adolescents with congenital heart disease were the experimental group ( p=0.02) and middle and high school students ( p=0.02). Quality of life was not associated with membership in the experimental group. However, males scored higher than females on quality of life measures ( p=0.02). CONCLUSIONS: It is essential for healthcare providers to apply various programs, including those targeted at accepting illness, improving autonomy and independently managing disease, to adolescents with congenital heart disease. PMID- 27400702 TI - Bolam with the benefit of hindsight. AB - The aims of this article are to consider the effects of hindsight bias on findings of negligence in medico-legal litigation and of the potential of the original Bolam direction to eliminate bias from the decision-making process. The Bolam test may have been expanded beyond its appropriate scope in the past, but these excesses have now largely been undone. It will be shown that Bolam still has an important role to play in tort cases. By considering breach of duty cases in which the Bolitho 'gloss' has been applied, attention is drawn to the potential dangers of disregarding practices within the medical profession. PMID- 27400703 TI - Fatal corrosive ingestion: A study from South and South-East Delhi, India (2005 2014). AB - The study presents a retrospective analysis of 64 cases of death resulting from ingestion of corrosive substances. The cases represented approximately 0.4% of all autopsies conducted and 13.6% of all fatal poisonings studied during the 10 year period from January 2005 to December 2014 at the Department of Forensic Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi. The data was analyzed with regard to age, sex, nature and source of corrosive substance used, survival period, cause and manner of death. Males (64.06%) outnumbered females (35.94%), with a male-to-female ratio of 1.78:1. The most common age group involved was 21-30 years (35.94%). Sulfuric acid (68.75%) presented as the most common corrosive substance ingested. Household cleaning substances (39.06%) were identified as a common source of such type of corrosive substance, but the exact source could not be identified in 56.26% of cases. In the majority of cases (46.88%) death was due to perforation peritonitis. Most of the victims (54.69%) succumbed to their injuries within a day of ingestion. In 87.5% of cases, the corrosive substance was consumed for suicidal purposes. A strict regulatory framework is required for the production, distribution, storage and use of corrosive substances. Preventive guidelines and creating awareness among the masses will go a long way towards curbing such unfortunate incidents. PMID- 27400704 TI - Host Selection, Growth, and Survival of Melonworm (Lepidoptera: Crambidae) on Four Cucurbit Crops Under Laboratory Conditions. AB - The melonworm, Diaphania hyalinata L. (Lepidoptera: Crambidae), is one of the most serious insect problems affecting cucurbit production. We evaluated the relative preference and suitability of yellow squash, zucchini, cucumber, and watermelon to melonworm by measuring its oviposition, larval feeding preference, survivorship, and developmental responses in the laboratory. Whole plants were used for oviposition study, whereas host leaf discs were used for all the other studies. Watermelon feeding resulted in the longest larval development period (14.3 d), greatest prepupal weights and survivals rates (92%; first instar to adult) among the four crops. However, for watermelon, adult oviposition preference (199.5 eggs/?), egg survival (70%), and larval feeding (4.1% defoliation) were numerically or statistically lowest, and larval head capsule widths and whole-body lengths were smallest. When differences occurred among these variables, yellow squash, zucchini, and cucumber were each typically higher (or quicker to develop) than watermelon. So why do melonworm adults not prefer watermelon, or at least select it as frequently as squash and cucumber when ovipositing? The answer likely is that there might be some variation in the important chemical components among these cucurbits. We suggest that comparison of kairomones and allomones from watermelon and related cucurbits would be very useful for determining the combination resulting in the lowest risk of damage to the more susceptible cucurbits (assuming the levels can be modified without seriously affecting the crops). PMID- 27400705 TI - Transmission of Squash vein yellowing virus to and From Cucurbit Weeds and Effects on Sweetpotato Whitefly (Hemiptera: Aleyrodidae) Behavior. AB - Since 2003, growers of Florida watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] have periodically suffered large losses from a disease caused by Squash vein yellowing virus (SqVYV), which is transmitted by the whitefly Middle East Asia Minor 1 (MEAM1), formerly Bemisia tabaci (Gennadius) biotype B. Common cucurbit weeds like balsam apple (Momordica charantia L.) and smellmelon [Cucumis melo var. dudaim (L.) Naud.] are natural hosts of SqVYV, and creeping cucumber (Melothria pendula L.) is an experimental host. Study objectives were to compare these weeds and 'Mickylee' watermelon as sources of inoculum for SqVYV via MEAM1 transmission, to determine weed susceptibility to SqVYV, and to evaluate whitefly settling and oviposition behaviors on infected vs. mock-inoculated (inoculated with buffer only) creeping cucumber leaves. We found that the lowest percentage of watermelon recipient plants was infected when balsam apple was used as a source of inoculum. Watermelon was more susceptible to infection than balsam apple or smellmelon. However, all weed species were equally susceptible to SqVYV when inoculated by whitefly. For the first 5 h after release, whiteflies had no preference to settle on infected vs. mock-inoculated creeping cucumber leaves. After 24 h, whiteflies preferred to settle on mock-inoculated leaves, and more eggs were laid on mock-inoculated creeping cucumber leaves than on SqVYV-infected leaves. The transmission experiments (source of inoculum and susceptibility) show these weed species as potential inoculum sources of the virus. The changing settling preference of whiteflies from infected to mock-inoculated plants could lead to rapid spread of virus in the agroecosystem. PMID- 27400706 TI - Initial posting-a critical stage in the employment cycle: lessons from the experience of government doctors in Gujarat, India. AB - BACKGROUND: With the critical shortage of government doctors serving in rural health centers in India, understanding the initial posting policies, processes, and practices become important from a retention point of view. The initial posting is a very critical stage of an employment cycle and could play an important role in influencing the key human resource for health outcomes such as turnover and performance. The current study aimed at exploring a rather unknown phenomenon of the initial posting-related processes, practices, and perceptions of Medical Officers working with the Public Health Department in Gujarat, India. METHODS: This was an exploratory study carried out in the state of Gujarat, India, that used qualitative methods first to document the extant initial posting policy with the help of document review and five Key Informant interviews; next, 19 in-depth interviews were carried out with Medical Officers to assess implementation of policies as well as processes and systems related to the initial posting of Medical Officers. A thematic framework approach was used to analyze qualitative data using NVIVO. RESULTS: The results indicate that there is no formal published or written initial posting policy in the state, and in the absence of a written and formal policy, the overall posting systems were perceived to be arbitrary by the study respondents. In the absence of any policy, the state has some unwritten informal practices such as posting the Medical Officers at their native places. Although this practice reflects a concern towards the Medical Officer's needs, such practices are not consistently applied indicating some inequity and possible implications over Medical Officers' retention and motivation. CONCLUSIONS: Initial posting is a critical aspect of an employment cycle, and the perceptions and experiences of MOs regarding the processes and practices involved in their initial posting can be crucial in influencing their performance and turnover rates. If long-term solutions are to be sought in addressing the availability and distribution of Medical Officers in the state, then there is a need to have clearly laid down initial posting-related policies that reflect the equity and consideration towards Medical Officers in placement-related matters. PMID- 27400709 TI - Introduction of a team-based care model in a general medical unit. AB - BACKGROUND: Alberta Health Services is a provincial health authority responsible for healthcare for more than four million people. The organization recognized a need to change its care delivery model to make care more patient- and family centred and use its health human resources more effectively by enhancing collaborative practice. A new care model including changes to how providers deliver care and skill mix changes to support the new processes was piloted on a medical unit in a large urban acute care hospital Evidence-based care processes were introduced, including an initial patient assessment and orientation, comfort rounds, bedside shift reports, patient whiteboards, Name Occupation Duty, rapid rounds, and team huddles. Small teams of nurses cared for a portion of patients on the unit. The model was intended to enhance safety and quality of care by allowing providers to work to full scope in a collaborative practice environment. METHODS: We evaluated the new model approximately one year after implementation using interviews with staff (n = 15), surveys of staff (n = 25 at baseline and at the final evaluation) and patients (n = 26 at baseline and 37 at the final evaluation), and administrative data pulled from organizational databases. RESULTS: Staff interviews revealed that overall, the new care processes and care teams worked quite well. Unit culture and collaboration were improved, as were role clarity, scope of practice, and patient care. Responses from staff surveys were also very positive, showing significant positive changes in most areas. Patient satisfaction surveys showed a few positive changes; scores overall were very high. Administrative data showed slight decreases in overall length of stay, 30-day readmissions, staff absenteeism, staff vacancies, and the overtime rate. We found no changes in unit length of stay, 30-day returns to emergency department, or nursing sensitive adverse events. CONCLUSIONS: Conclusions from the evaluation were positive, providing initial support for the idea of the collaborative practice model vision for adult medical units across Alberta. There were also a few positive effects on patient care suggesting that models such as this one could improve the organization's ability to deliver sustainable, high quality, patient- and family-centred care without compromising quality. PMID- 27400708 TI - The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b(+) Ly6C(hi) cells to tumor tissue reduces tumor growth. AB - BACKGROUND: Previous work has demonstrated immunomodulatory, anti-tumor, anti metastatic and anti-angiogenic effects of the small molecule quinoline-3 carboxamide tasquinimod in pre-clinical cancer models. To better understand the anti-tumor effects of tasquinimod in transplantable tumor models, we have evaluated the impact of the compound both on recruitment of myeloid cells to tumor tissue and on tumor-induced myeloid cell expansion as these cells are known to promote tumor development. METHODS: Mice bearing subcutaneous 4 T1 mammary carcinoma tumors were treated with tasquinimod in the drinking water. A BrdU based flow cytometry assay was utilized to assess the impact of short-term tasquinimod treatment on myeloid cell recruitment to tumors. Additionally, long term treatment was performed to study the anti-tumor effect of tasquinimod as well as its effects on splenic myeloid cells and their progenitors. Myeloid cell populations were also immune-depleted by in vivo antibody treatment. RESULTS: Short-term tasquinimod treatment did not influence the proliferation of splenic Ly6C(hi) and Ly6G(hi) cells, but instead reduced the influx of Ly6C(hi) cells to the tumor. Treatment with tasquinimod for various periods of time after tumor inoculation revealed that the anti-tumor effect of this compound mainly operated during the first few days of tumor growth. Similar to tasquinimod treatment, antibody-mediated depletion of Ly6C(hi) cells within that same time frame, caused reduced tumor growth, thereby confirming a significant role for these cells in tumor development. Additionally, long-term tasquinimod treatment reduced the splenomegaly and expansion of splenic myeloid cells during a later phase of tumor development. In this phase, tasquinimod normalized the tumor-induced alterations in myeloerythroid progenitor cells in the spleen but had only limited impact on the same populations in the bone marrow. CONCLUSIONS: Our results indicate that tasquinimod treatment reduces tumor growth by operating early after tumor inoculation and that this effect is at least partially caused by reduced recruitment of Ly6C(hi) cells to tumor tissue. Long-term treatment also reduces the number of splenic myeloid cells and myeloerythroid progenitors, but these effects did not influence established rapidly growing tumors. PMID- 27400707 TI - The recombination dynamics of Staphylococcus aureus inferred from spA gene. AB - BACKGROUND: Given the role of spA as a pivotal virulence factor decisive for Staphylococcus aureus ability to escape from innate and adaptive immune responses, one can consider it as an object subject to adaptive evolution and that variations in spA may uncover pathogenicity variations. RESULTS: The population genetic structure was deduced from the extracellular domains of SpA gene sequence (domains A-E and the X-region) and compared to the MLST-analysis of 41 genetically diverse methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus strains. Incongruence between tree topologies was noticeable and in the inferred spA tree most MSSA isolates were clustered in a distinct group. Conversely, the distribution of strains according to their spA-type was not always congruent with the tree inferred from the complete spA gene foreseeing that spA is a mosaic gene composed of different segments exhibiting different evolutionary histories. Evidences of a network-like organization were identified through several conflicting phylogenetic signals and indeed several intragenic recombination events (within subdomains of the gene) were detected within and between CC's of MRSA strains. The alignment of SpA sequences enabled the clustering of several isoforms as a result of non-randomly distributed amino acid variations, located in two clusters of polymorphic sites in domains D to B and Xr (a). Nevertheless, evidences of cluster specific structural arrangements were detected reflecting alterations on specific residues with potential impact on S. aureus pathogenicity. CONCLUSIONS: The detection of positive selection operating on spA combined with frequent non-synonymous mutations, domain duplication and frequent intragenic recombination events represent important mechanisms acting in the evolutionary adaptive mechanism promoting spA genetic plasticity. These findings argue that crucial allelic forms correlated with pathogenicity can be identified by sequences analysis enabling the design of more robust schemes. PMID- 27400710 TI - Variations in area-level disadvantage of Australian registered fitness trainers usual training locations. AB - BACKGROUND: Leisure-time physical activity and strength training participation levels are low and socioeconomically distributed. Fitness trainers (e.g. gym/group instructors) may have a role in increasing these participation levels. However, it is not known whether the training location and characteristics of Australian fitness trainers vary between areas that differ in socioeconomic status. METHODS: In 2014, a sample of 1,189 Australian trainers completed an online survey with questions about personal and fitness industry-related characteristics (e.g. qualifications, setting, and experience) and postcode of their usual training location. The Australian Bureau of Statistics 'Index of Relative Socioeconomic Disadvantage' (IRSD) was matched to training location and used to assess where fitness professionals trained and whether their experience, qualification level and delivery methods differed by area-level disadvantage. Linear regression analysis was used to examine the relationship between IRSD score and selected characteristics adjusting for covariates (e.g. sex, age). RESULTS: Overall, 47 % of respondents worked in areas within the three least disadvantaged deciles. In contrast, only 14.8 % worked in the three most disadvantaged deciles. In adjusted regression models, fitness industry qualification was positively associated with a higher IRSD score (i.e. working in the least-disadvantaged areas) (Cert III: ref; Cert IV beta:13.44 [95 % CI 3.86 23.02]; Diploma beta:15.77 [95 % CI: 2.17-29.37]; Undergraduate beta:23.14 [95 % CI: 9.41-36.86]). CONCLUSIONS: Fewer Australian fitness trainers work in areas with high levels of socioeconomic disadvantaged areas than in areas with low levels of disadvantage. A higher level of fitness industry qualifications was associated with working in areas with lower levels of disadvantage. Future research should explore the effectiveness of providing incentives that encourage more fitness trainers and those with higher qualifications to work in more socioeconomically disadvantaged areas. PMID- 27400711 TI - Assessing the economic burden of Alzheimer's disease patients first diagnosed by specialists. AB - BACKGROUND: It is not known if there is a differential impact on Alzheimer's disease (AD) diagnosis and outcomes if/when patients are diagnosed with cognitive decline by specialists versus non-specialists. This study examined the cost trajectories of Medicare beneficiaries initially diagnosed by specialists compared to similar patients who received their diagnosis in primary care settings. METHODS: Patients with >=2 claims for AD were selected from de identified administrative claims data for US Medicare beneficiaries (5 % random sample). The earliest observed diagnosis of cognitive decline served as the index date. Patients were required to have continuous Medicare coverage for >=12 months pre-index (baseline) and >=12 months following the first AD diagnosis, allowing for up to 3 years from index to AD diagnosis. Time from index date to AD diagnosis was compared between those diagnosed by specialists (i.e., neurologist, psychiatrist, or geriatrician) versus non-specialists using Kaplan-Meier analyses with log-rank tests. Patient demographics, Charlson Comorbidity Index (CCI) during baseline, and annual all-cause medical costs (reimbursed by Medicare) in baseline and follow-up periods were compared across propensity-score matched cohorts. RESULTS: Patients first diagnosed with cognitive decline by specialists (n = 2593) were younger (78.8 versus 80.8 years old), more likely to be male (40 % versus 34 %), and had higher CCI scores and higher medical costs at baseline than those diagnosed by non-specialists (n = 13,961). However, patients diagnosed by specialists had a significantly shorter time to AD diagnosis, both before and after matching (mean [after matching]: 3.5 versus 4.6 months, p < 0.0001). In addition, patients diagnosed by specialists had significantly lower average total all-cause medical costs in the first 12 months after their index date, a finding that persisted after matching ($19,824 versus $25,863, p < 0.0001). Total per patient annual medical costs were similar for the two groups starting in the second year post-index. CONCLUSIONS: Before and after matching, patients diagnosed by a specialist had a shorter time to AD diagnosis and incurred lower costs in the year following the initial cognitive decline diagnosis. Differences in costs converged during subsequent years. This suggests that seeking care from specialists may yield more timely diagnosis, appropriate care and reduced costs among those with cognitive decline. PMID- 27400712 TI - Rubus occidentalis alleviates hyperalgesia induced by repeated intramuscular injection of acidic saline in rats. AB - BACKGROUND: The purpose of this study was to evaluate the antinociceptive effect of black raspberry (Rubus occidentalis) fruit extract (ROE) in a rat model of chronic muscle pain and examine the mechanisms involved. METHODS: Adult male Sprague-Dawley rats were used, and chronic muscle pain was induced by two injections of acidic saline into one gastrocnemius muscle. For the first experiment, 50 rats were randomly assigned to five groups. After the development of hyperalgesia, rats were injected intraperitoneally with 0.9 % saline or ROE (10, 30, 100, or 300 mg/kg). For the second experiment, 70 rats were randomly assigned to seven groups. Rats were injected intraperitoneally with saline, yohimbine, dexmedetomidine, prazosin, atropine, mecamylamine, or naloxone after the development of hyperalgesia. Ten minutes later, ROE (300 mg/kg) was administered intraperitoneally. For both experiments, the mechanical withdrawal threshold (MWT) was evaluated with von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at 15, 30, 45, 60, 80, 100, and 120 min, 24 and 48 h after the drug administration. RESULTS: Compared with the control group, the MWT significantly increased up to 45 min after injection of ROE 100 mg/kg and up to 60 min after injection of ROE 300 mg/kg, respectively. Injection of ROE together with yohimbine or mecamylamine significantly decreased the MWT compared with the effect of ROE alone, while ROE together with dexmedetomidine significantly increased the MWT. CONCLUSIONS: ROE showed antinociceptive activity against induced chronic muscle pain, which may be mediated by alpha2-adrenergic and nicotinic cholinergic receptors. PMID- 27400713 TI - Clinical and neuropsychological characteristics of general paresis misdiagnosed as primary psychiatric disease. AB - BACKGROUND: Neurosyphilis is caused by the invasion of Treponema pallidum into the central nervous system. General paresis (GP) is a type of neurosyphilis. The main manifestation of general paresis is dementia; however, this is different from the other types of dementia, which can be cured by adequate doses of penicillin in the early stage. Neurosyphilis is the "great imitator" because it can mimic many types of medical disorders. In addition, the manifestations of neurosyphilis are not typical. Psychiatric disorders as a cause of general paresis have become more common due to the use of antibiotics. Patients with a psychiatric manifestation are often misdiagnosed. The purpose of this study was to explore the differences in the clinical and neuropsychological characteristics of general paresis between patients misdiagnosed as having a primary psychiatric disease and patients diagnosed correctly upon seeing a doctor. The results may assist clinicians in the early identification of neurosyphilis with a mental disorder. METHOD: The demographic and clinical manifestations, laboratory tests, and neuroimaging and neuropsychological characteristics were analysed in 55 general paresis patients with psychiatric disorders, including 29 patients misdiagnosed as primary psychiatric disease and 26 patients diagnosed as having general paresis after being seen once by a doctor. RESULT: All of the patients had positive assay results for cerebral spinal fluid (CSF) Treponema pallidum hemagglutination (TPHA). Only 43.3 % of misdiagnosed patients and 30.8 % of general paresis patients had positive results for the CSF rapid plasma reagin (RPR) test; 96.4 % patients had abnormal neuroimaging. Mood disturbances were the most common psychiatric disorder in the general paresis patients, especially agitation, between the two groups (patients with general paresis who were misdiagnosed as having primary psychiatric disease and patients who had never been misdiagnosed) (p = 0.011). CONCLUSION: Our findings reinforce the importance of performing serologic testing for syphilis. This should be a part of the evaluation of patients with psychiatric disorders, especially patients with cognitive impairment. When the syphilis serology is positive, the patient should be examined thoroughly for neurosyphilis by lumbar puncture. Brain imaging could also aid the physician in discriminating these patients from those with a functional mental disorder. PMID- 27400714 TI - Platelet-Rich Plasma Activates Proinflammatory Signaling Pathways and Induces Oxidative Stress in Tendon Fibroblasts. AB - BACKGROUND: Tendon injuries are one of the most common musculoskeletal conditions in active patients. Platelet-rich plasma (PRP) has shown some promise in the treatment of tendon disorders, but little is known as to the mechanisms by which PRP can improve tendon regeneration. PRP contains numerous different growth factors and cytokines that activate various cellular signaling cascades, but it has been difficult to determine precisely which signaling pathways and cellular responses are activated after PRP treatment. Additionally, macrophages play an important role in modulating tendon regeneration, but the influence of PRP on determining whether macrophages assume a proinflammatory or anti-inflammatory phenotype remains unknown. PURPOSE: To use genome-wide expression profiling, bioinformatics, and protein analysis to determine the cellular pathways activated in fibroblasts treated with PRP. The effect of PRP on macrophage polarization was also evaluated. STUDY DESIGN: Controlled laboratory study. METHODS: Tendon fibroblasts or macrophages from rats were cultured and treated with either platelet-poor plasma (PPP) or PRP. RNA or protein was isolated from cells and analyzed using microarrays, quantitative polymerase chain reaction, immunoblotting, or bioinformatics techniques. RESULTS: Pathway analysis determined that the most highly induced signaling pathways in PRP-treated tendon fibroblasts were TNFalpha and NFkappaB pathways. PRP also downregulated the expression of extracellular matrix genes and induced the expression of autophagy related genes and reactive oxygen species (ROS) genes and protein markers in tendon fibroblasts. PRP failed to have a major effect on markers of macrophage polarization. CONCLUSION: PRP induces an inflammatory response in tendon fibroblasts, which leads to the formation of ROS and the activation of oxidative stress pathways. PRP does not appear to significantly modulate macrophage polarization. CLINICAL RELEVANCE: PRP might act by inducing a transient inflammatory event, which could then trigger a tissue regeneration response. PMID- 27400715 TI - Predictors of Length of Career After Hip Arthroscopy for Femoroacetabular Impingement in Professional Hockey Players. AB - BACKGROUND: Previous studies have shown that professional hockey players return to sport at a high rate after hip arthroscopy, although it is unknown how long players continue to compete at a professional level after surgery. PURPOSE: To determine the prevalence of athletes who continued playing in the National Hockey League (NHL) for a minimum of 5 years after hip arthroscopy for treatment of symptomatic femoroacetabular impingement (FAI) and to determine predictors associated with length of career. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 60 professional hockey players (69 hips) underwent hip arthroscopy for FAI by a single surgeon between 2005 and 2010. Data were retrieved from NHL.com and Hockey-reference.com regarding information on each player's professional career. Position played, age, surgical procedure, and intraoperative findings were also used in data analysis. RESULTS: There were 12 centers, 15 defensemen, 16 goalies, and 17 wings studied. Of the 60 athletes, 40 (67%) continued to play professionally a minimum of 5 years after hip arthroscopy. As of the 2015 season, the mean length of a player's NHL career was 13.7 years (range, 2-27 years), with an average of 5.9 years played after hip arthroscopy. There was no difference in length of career or years played when goalies were compared with other positions (P = .760). Length of career and years played after arthroscopy correlated with age at surgery (r = 0.799 and -0.408, respectively). Players who played >=5 years after arthroscopy were significantly younger than those who did not (25 vs 30 years; P = .001). Athletes who played <5 years after arthroscopy had a longer average duration of symptoms before surgery when compared with those who played >=5 years (20.2 vs 9.3 months; P = .049). There were no differences in length of career or years played after arthroscopy based on type of labral treatment. CONCLUSION: Professional NHL players who underwent hip arthroscopy for FAI were able to continue playing for an average of 5.9 years after surgery, with 67% playing a minimum of 5 years postoperatively. Younger age and shorter duration of symptoms at time of surgery correlated with greater length of career and years played after hip arthroscopy. Players who did not play a minimum of 5 years postoperatively had significantly longer duration of symptoms before surgery. The study data support early arthroscopic treatment of professional hockey players with symptomatic FAI. PMID- 27400716 TI - Functional Recovery in Osteoarthritic Chondrocytes Through Hyaluronic Acid and Platelet-Rich Plasma-Inhibited Infrapatellar Fat Pad Adipocytes. AB - BACKGROUND: Recent studies have shown evidence that higher adiposity in the infrapatellar fat pad (IFP) induces inflammatory phenotypes in the knee joint and thereby contributes to the development and progression of osteoarthritis (OA). In particular, IFP adipocyte-derived inflammatory cytokines participate in pathological events. Our previous research has already addressed the therapeutic efficacy of hyaluronic acid and platelet-rich plasma (HA+PRP), including the promotion of cartilage regeneration and the inhibition of inflammation. The current study aimed to explore the remedial action of coadministered HA+PRP in OA recovery via IFP adipocyte inhibition. HYPOTHESIS: HA+PRP repairs OA articular cartilage by inhibiting the release of adipokines from IFP adipocytes. STUDY DESIGN: Controlled laboratory study. METHODS: IFP adipocytes and articular chondrocytes were obtained from 10 patients with OA, and the effects of releasates containing cytokines and adipokines in IFP adipocyte-derived conditioned medium (IACM) on articular chondrocytes and IFP adipocytes themselves were evaluated. The therapeutic efficacy of exogenous HA+PRP was determined through its administration to cocultured IFP adipocytes and articular chondrocytes and further demonstrated in a 3-dimensional (3D) arthritic neocartilage model. RESULTS: The IACM and IFP adipocyte-induced microenvironment could induce dedifferentiated and inflammatory phenotypes in articular chondrocytes. HA+PRP decreased the inflammatory potential of IFP adipocytes through the profound inhibition of cytokines and adipokines. The IACM-mediated and -reduced cartilaginous extracellular matrix could also be recovered through HA+PRP in the 3D arthritic neocartilage model. CONCLUSION: IFP adipocyte-derived releasates mediated inflammatory response dedifferentiation in chondrocytes, which was recovered through HA+PRP administration. CLINICAL RELEVANCE: Our findings demonstrated that HA+PRP effectively diminished IFP adipocyte-promoted inflammation in articular chondrocytes, indicating that the IFP could be a potential therapeutic target for OA therapy. PMID- 27400717 TI - Evaluation of Repair Tension in Arthroscopic Rotator Cuff Repair: Does It Really Matter to the Integrity of the Rotator Cuff? AB - BACKGROUND: Repair tension of a torn rotator cuff can affect healing after repair. However, a measurement of the actual tension during arthroscopic rotator cuff repair is not feasible. The relationship between repair tension and healing of a rotator cuff repair remains unclear. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effect of repair tension on healing at the repair site. The hypothesis was that repair tension would be a major factor in determining the anatomic outcome of rotator cuff repair. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Arthroscopic rotator cuff repairs (132 patients) for full thickness rotator cuff tears were analyzed. An intraoperative model was designed for the estimation of repair tension using a tensiometer. Magnetic resonance imaging (MRI) was performed approximately 1 year (mean [+/-SD], 12.7 +/- 3.2 months) postoperatively for the evaluation of healing at the repair site. Multivariable analysis was performed for tear size, amount of retraction, and fatty degeneration (FD) of rotator cuff muscles. RESULTS: The mean repair tension measured during the arthroscopic procedure was 28.5 +/- 23.1 N. There was a statistically significant correlation between tension and tear size (Pearson correlation coefficient [PCC], 0.529; P < .001), amount of retraction (PCC, 0.619; P < .001), and FD of the supraspinatus (Spearman correlation coefficient [SCC], 0.308; P < .001) and infraspinatus (SCC, 0.332; P < .001). At the final follow-up (12.7 +/- 3.2 months), healing failure was observed in 18.2% (24/132), and repair tension also showed a significant inverse correlation with healing at the repair site (SCC, 0.195; P = .025). However, when sex, age, tear size, amount of retraction, tendon quality, and FD of rotator cuff muscles were included for multivariable logistic regression analysis, only FD of the infraspinatus showed an association with the anatomic outcome of repair (Exp(B) = 0.596; P = .010). CONCLUSION: Our intraoperative model for the estimation of rotator cuff repair tension showed an inverse correlation of repair tension with healing at the repair site, suggesting that complete healing is less likely with high-tension repairs. A significant association was observed on MRI between a high level of FD of the infraspinatus and repaired tendon integrity. PMID- 27400718 TI - Should We Limit Innings Pitched After Ulnar Collateral Ligament Reconstruction in Major League Baseball Pitchers? AB - BACKGROUND: Ulnar collateral ligament reconstruction (UCLR) has become a common procedure among Major League Baseball (MLB) pitchers. It is unclear if a limit on innings pitched after UCLR should be instituted to prevent revision UCLR. HYPOTHESIS: Number of innings pitched and number of pitches thrown after UCLR will not affect whether a pitcher requires a revision UCLR. STUDY DESIGN: Descriptive laboratory study. METHODS: All MLB pitchers between 1974 and 2015 who pitched at least 1 full season after UCLR were included in this study. Pitch counts and innings pitched for the first full season after UCLR as well as total pitch count and total innings pitched were recorded. Pitch counts and innings pitched were compared among players who required revision UCLR and those who did not. RESULTS: Overall, 154 pitchers were included. Of these, 135 pitchers did not require revision UCLR while 19 underwent revision UCLR. No significant difference existed between pitchers who underwent revision UCLR and those who did not when comparing number of innings pitched in the season after UCLR (79.4 +/- 46.7 vs 90.1 +/- 58.6; P = .9016), number of pitches thrown in the season after UCLR (1233.2 +/- 710.4 vs 1449.2 +/- 904.1; P = .7337), number of innings pitched in the pitcher's career after UCLR (357.4 +/- 312.0 vs 399.3 +/- 446.4; P = .6945), and number of pitches thrown in the pitcher's career after UCLR (5632.7 +/- 4583.9 vs 5674.7 +/- 5755.4; P = .4789), respectively. Furthermore, no difference existed in revision rate between pitchers who pitched more or less than 180 innings in the first full season after UCLR (P = .6678). CONCLUSION: The number of innings pitched and number of pitches thrown in the first full season as well as over a player's career after UCLR are not associated with an increased risk of a pitcher requiring revision UCLR. PMID- 27400719 TI - Structural Basis for Recombinatorial Permissiveness in the Generation of Anaplasma marginale Msp2 Antigenic Variants. AB - Sequential expression of outer membrane protein antigenic variants is an evolutionarily convergent mechanism used by bacterial pathogens to escape host immune clearance and establish persistent infection. Variants must be sufficiently structurally distinct to escape existing immune effectors yet retain the core structural elements required for localization and function within the outer membrane. We examined this balance using Anaplasma marginale, which generates antigenic variants in the outer membrane protein Msp2 using gene conversion. The overwhelming majority of Msp2 variants expressed during long-term persistent infection are mosaics, derived by recombination of oligonucleotide segments from multiple alleles to form unique hypervariable regions (HVR). As a result, the mosaics are not under long-term selective pressure to encode a functional protein; consequently, we hypothesized that the Msp2 HVR is structurally permissive for mosaic expression. Using an integrated approach of predictive modeling with determination of the native Msp2 protein structure and function, we demonstrate that structured elements, most notably, beta-sheets, are significantly concentrated in the highly conserved N- and C-terminal domains. In contrast, the HVR is overwhelmingly a random coil, with the structured alpha helices and beta-sheets being confined to the genomically defined structural tethers that separate the antigenically variable microdomains. This structure is supported by the surface exposure of the HVR microdomains and the slow diffusion type porin function in native Msp2. Importantly, the predominance of the random coil provides plasticity for the formation of functional HVR mosaics and realization of the full potential of segmental gene conversion to dramatically expand the variant repertoire. PMID- 27400720 TI - Tryptophan Codon-Dependent Transcription in Chlamydia pneumoniae during Gamma Interferon-Mediated Tryptophan Limitation. AB - In evolving to an obligate intracellular niche, Chlamydia has streamlined its genome by eliminating superfluous genes as it relies on the host cell for a variety of nutritional needs like amino acids. However, Chlamydia can experience amino acid starvation when the human host cell in which the bacteria reside is exposed to interferon gamma (IFN-gamma), which leads to a tryptophan (Trp) limiting environment via induction of the enzyme indoleamine-2,3-dioxygenase (IDO). The stringent response is used to respond to amino acid starvation in most bacteria but is missing from Chlamydia Thus, how Chlamydia, a Trp auxotroph, responds to Trp starvation in the absence of a stringent response is an intriguing question. We previously observed that C. pneumoniae responds to this stress by globally increasing transcription while globally decreasing translation, an unusual response. Here, we sought to understand this and hypothesized that the Trp codon content of a given gene would determine its transcription level. We quantified transcripts from C. pneumoniae genes that were either rich or poor in Trp codons and found that Trp codon-rich transcripts were increased, whereas those that lacked Trp codons were unchanged or even decreased. There were exceptions, and these involved operons or large genes with multiple Trp codons: downstream transcripts were less abundant after Trp codon-rich sequences. These data suggest that ribosome stalling on Trp codons causes a negative polar effect on downstream sequences. Finally, reassessing previous C. pneumoniae microarray data based on codon content, we found that upregulated transcripts were enriched in Trp codons, thus supporting our hypothesis. PMID- 27400721 TI - Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection. AB - One of the least understood aspects of the bacterium Streptococcus pneumoniae (pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized "index" pups to uncolonized "contact" pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection. PMID- 27400722 TI - Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia. AB - Vitamin D (VitD) has a role in the regulation of calcium and phosphate metabolism and in addition impacts the activity of the immune system. VitD deficiency might be linked to increased susceptibility to respiratory tract infection. The aim of the present study was to characterize the impact of VitD deficiency on the susceptibility to bacterial infection in murine models. C57BL/6N mice were fed a diet with or without VitD for 10 weeks. The VitD-deficient or -sufficient mice were infected with Pseudomonas aeruginosa or Streptococcus pneumoniae The colonization and inflammatory response in the lung were analyzed at defined time points. The serum 25-hydroxy-VitD concentration was significantly lower in mice on the VitD-deficient diet. In infection experiments with Pseudomonas aeruginosa or Streptococcus pneumoniae, no differences could be observed in the numbers of viable bacteria or in differential cell counts in the bronchoalveolar lavage fluids. Measurements of inflammatory cytokines (KC and interleukin-1beta [IL 1beta]) did not show significant differences between the groups. In conclusion, VitD-deficient animals did not show significantly increased susceptibility to infection or an altered course of infection. The immune systems of humans and mice likely respond differently to VitD. Murine models are likely not appropriate for drawing conclusions on the role of VitD in human pulmonary host defense. PMID- 27400723 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27400724 TI - Heart transplantation as salvage therapy for progressive prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE). AB - BACKGROUND: Prosthetic valve endocarditis (PVE) has the highest in-hospital mortality among all cases of infective endocarditis (IE), it is estimated at about 40 %. Orthotopic heart transplantation (OHT) as a measure of last resort, may be considered in selected cases where repeated surgical procedures and conservative efforts have failed to eradicate persistent or recurrent IE. Only few clinical data are available regarding this rare indication for OHT, since active IE has traditionally been considered as a contraindication for OHT. CASE PRESENTATION: We report on a 55 year old male patient who underwent prosthetic valve replacement with a mechanical valved conduit ten years ago and developed now persistent PVE with severe complications due to methicillin-resistant Staphylococcus epidermidis (MRSE). Repeated surgical procedures and conservative efforts have failed to eradicate the pathogen. Regarding the lack of curative options, salvage OHT was discussed as a measure of last resort. 28 months after the first diagnosis of PVE, the patient was successfully transplanted and is now doing well under close follow-up (6 months post-OHT). CONCLUSIONS: PVE remains a challenging condition regarding diagnosis and treatment. The presented case underscores the urgent need for an integrated and multidisciplinary approach to patients with suspected and definitive IE - especially in PVE. OHT might be a feasible measure of last resort in selected patients with IE. Our case report adds published clinical experience to this rarely performed procedure and consolidates previous findings. PMID- 27400727 TI - Validity criteria for Fermi's golden rule scattering rates applied to metallic nanowires. AB - Fermi's golden rule underpins the investigation of mobile carriers propagating through various solids, being a standard tool to calculate their scattering rates. As such, it provides a perturbative estimate under the implicit assumption that the effect of the interaction Hamiltonian which causes the scattering events is sufficiently small. To check the validity of this assumption, we present a general framework to derive simple validity criteria in order to assess whether the scattering rates can be trusted for the system under consideration, given its statistical properties such as average size, electron density, impurity density et cetera. We derive concrete validity criteria for metallic nanowires with conduction electrons populating a single parabolic band subjected to different elastic scattering mechanisms: impurities, grain boundaries and surface roughness. PMID- 27400725 TI - Deletion of the type-1 interferon receptor in APPSWE/PS1DeltaE9 mice preserves cognitive function and alters glial phenotype. AB - A neuro-inflammatory response is evident in Alzheimer's disease (AD), yet the precise mechanisms by which neuro-inflammation influences the progression of Alzheimer's disease (AD) remain poorly understood. Type-1 interferons (IFNs) are master regulators of innate immunity and have been implicated in multiple CNS disorders, however their role in AD progression has not yet been fully investigated. Hence, we generated APPSWE/PS1DeltaE9 mice lacking the type-1 IFN alpha receptor-1 (IFNAR1, APPSWE/PS1DeltaE9 x IFNAR1(-/-)) aged to 9 months to investigate the role of type-1 IFN signaling in a well-validated model of AD. APPSWE/PS1DeltaE9 x IFNAR1(-/-) mice displayed a modest reduction in Abeta monomer levels, despite maintenance of plaque deposition. This finding correlated with partial rescue of spatial learning and memory impairments in the Morris water maze in comparison to APPSWE/PS1DeltaE9 mice. Q-PCR identified a reduced type-1 IFN response and modulated pro-inflammatory cytokine secretion in APPSWE/PS1DeltaE9 x IFNAR1(-/-) mice compared to APPSWE/PS1DeltaE9 mice. Interestingly, immunohistochemistry displayed enhanced astrocyte reactivity but attenuated microgliosis surrounding amyloid plaque deposits in APPSWE/PS1DeltaE9 x IFNAR1(-/-) mice in comparison to APPSWE/PS1DeltaE9 mice. These APPSWE/PS1DeltaE9 x IFNAR1(-/-) microglial populations demonstrated an anti inflammatory phenotype that was confirmed in vitro by soluble Abeta1-42 treatment of IFNAR1(-/-) primary glial cultures. Our findings suggest that modulating neuro inflammatory responses by suppressing type-1 IFN signaling may provide therapeutic benefit in AD. PMID- 27400726 TI - Being an Informed Consumer of Health Information and Assessment of Electronic Health Literacy in a National Sample of Internet Users: Validity and Reliability of the e-HLS Instrument. AB - BACKGROUND: The Internet, with its capacity to provide information that transcends time and space barriers, continues to transform how people find and apply information to their own lives. With the current explosion in electronic sources of health information, including thousands of websites and hundreds of mobile phone health apps, electronic health literacy is gaining an increasing prominence in health and medical research. An important dimension of electronic health literacy is the ability to appraise the quality of information that will facilitate everyday health care decisions. Health information seekers explore their care options by gathering information from health websites, blogs, Web based forums, social networking websites, and advertisements, despite the fact that information quality on the Internet varies greatly. Nonetheless, research has lagged behind in establishing multidimensional instruments, in part due to the evolving construct of health literacy itself. OBJECTIVE: The purpose of this study was to examine psychometric properties of a new electronic health literacy (ehealth literacy) measure in a national sample of Internet users with specific attention to older users. Our paper is motivated by the fact that ehealth literacy is an underinvestigated area of inquiry. METHODS: Our sample was drawn from a panel of more than 55,000 participants maintained by Knowledge Networks, the largest national probability-based research panel for Web-based surveys. We examined the factor structure of a 19-item electronic Health Literacy Scale (e HLS) through exploratory factor analysis (EFA) and confirmatory factor analysis, internal consistency reliability, and construct validity on sample of adults (n=710) and a subsample of older adults (n=194). The AMOS graphics program 21.0 was used to construct a measurement model, linking latent factors obtained from EFA with 19 indicators to determine whether this factor structure achieved a good fit with our entire sample and the subsample (age >= 60 years). Linear regression analyses were performed in separate models to examine: (1) the construct validity of the e-HLS and (2) its association with respondents' demographic characteristics and health variables. RESULTS: The EFA produced a 3-factor solution: communication (2 items), trust (4 items), and action (13 items). The 3 factor structure of the e-HLS was found to be invariant for the subsample. Fit indices obtained were as follows: full sample: chi(2) (710)=698.547, df=131, P<.001, comparative fit index (CFI)=0.94, normed fit index (NFI)=0.92, root mean squared error of approximation (RMSEA)=0.08; and for the older subsample (age >= 60 years): chi(2) (194)=275.744, df=131, P<.001, CFI=0.95, NFI=0.90, RMSEA=0.08. CONCLUSIONS: The analyses supported the e-HLS validity and internal reliability for the full sample and subsample. The overwhelming majority of our respondents reported a great deal of confidence in their ability to appraise the quality of information obtained from the Internet, yet less than half reported performing quality checks contained on the e-HLS. PMID- 27400728 TI - Early change in faecal calprotectin predicts primary non-response to anti TNFalpha therapy in Crohn's disease. AB - OBJECTIVE: The early identification of primary non-response to anti-TNFalpha therapy facilitates the timely management of patients with Crohn's disease (CD). A recent, pilot study to detect prognostic markers of early response to anti TNFalpha therapy identified the two genes coding for the calprotectin subunits (S100A8, S100A9) to be among the most highly expressed gene transcripts in non responders. This study tests the hypothesis that measurements of faecal calprotectin (FCAL) pre- and post-anti-TNFalpha induction can predict primary non response. METHODS: Retrospective study of 32 CD patients treated over a two-year period. Outcomes were assessed at 6 months based on clinical activity scores and the use of corticosteroids: (a) remission: Harvey-Bradshaw index (HBI) < 5, off corticosteroids >2 months; (b) response: drop in HBI >3, off corticosteroids; (c) non-response: DeltaFCAL (and DeltaCRP, respectively) was calculated as (FCAL post induction - FCAL pre-induction) * 100/FCAL pre induction. RESULTS: At 6 months, 23 (72%) patients had responded (median (interquartile range) HBI: 4 (3-5), FCAL: 55 (27-146)), 17 (73%) of whom were in remission [HBI: 3 (2.5-4) and FCAL: 42 (16 115)]. There was a significant difference in the DeltaFCAL from baseline to post induction in the three groups (p < 0.0001). Comparing non-responders to combined response and remission groups, the AUC of DeltaFCAL to predict outcome at 6 months was 0.97. Using ROC analysis, a Delta70% returned a sensitivity and specificity of 99% and 96%, respectively (likelihood ratio, LR= 23). DeltaCRP did not predict 6 months outcomes. CONCLUSIONS: A drop in FCAL <70% after induction predicts primary non-response to anti-TNFalpha in CD. PMID- 27400729 TI - Persistent mechanical stretch-induced calcium overload and MAPK signal activation contributed to SCF reduction in colonic smooth muscle in vivo and in vitro. AB - Gastrointestinal (GI) distention is a common pathological characteristic in most GI motility disorders (GMDs), however, their detail mechanism remains unknown. In this study, we focused on Ca2+ overload of smooth muscle, which is an early intracellular reaction to stretch, and its downstream MAPK signaling and also reduction of SCF in vivo and in vitro. We successfully established colonic dilation mouse model by keeping incomplete colon obstruction for 8 days. The results showed that persistent colonic dilation clearly induced Ca2+ overload and activated all the three MAPK family members including JNK, ERK and p38 in smooth muscle tissues. Similar results were obtained from dilated colon of patients with Hirschsprung's disease and stretched primary mouse colonic smooth muscle cells (SMCs). Furthermore, we demonstrated that persistent stretch-induced Ca2+ overload was originated from extracellular Ca2+ influx and endoplasmic reticulum (ER) Ca2+ release identified by treating with different Ca2+ channel blockers, and was responsible for the persistent activation of MAPK signaling and SCF reduction in colonic SMCs. Our results suggested that Ca2+ overload caused by smooth muscle stretch led to persistent activation of MAPK signaling which might contribute to the decrease of SCF and development of the GMDs. PMID- 27400730 TI - Treatment of gynecological cancers diagnosed during pregnancy. AB - Because of a notable increase in age at delivery, the incidence of malignancy diagnosed during pregnancy has substantially increased. This review aims to summarize the literature and expert knowledge on gynecologic cancers diagnosed in pregnancy regarding epidemiology, examination and staging procedures, description of treatment modalities and management of gynecological malignancies with special interest in cervical and ovarian cancer. Thorough attention is paid to the surgery and chemotherapy administration for early-stage cervical cancer diagnosed during pregnancy. PMID- 27400731 TI - Spine loading during the application and removal of lifting slings: the effects of patient weight, bed height and work method. AB - The biomechanical loading on the lumbar spine was assessed as 12 female nurses applied and removed slings under two patients of differing weights (54 and 100 kg), using two work methods, and while working at three bed heights (56, 71, 93 cm). Three-dimensional spine loads at the L2/L3, L3/L4, L4/L5 and L5/S1 disc levels were measured using a validated EMG-assisted biomechanical model. Anterior/posterior (A/P) shear loading at the L5/S1 level consistently exceeded the tolerance threshold limit for disc failure. The peak compression values exceeded the 3400 N tolerance threshold for several participants when placing the sling under the 100-kg patient. In general, working from both sides of the bed generated slightly higher A/P shear loading than the one-sided method. Raising the bed significantly decreased compression and A/P shear forces. Therefore, raising the bed to at least the nurse's knuckle height is recommended when applying and removing patient slings. Practitioners Summary: We investigated the spine loading associated with placing and removing slings used for the mechanised lifting of patients. Peak compression and anterior shear forces exceeded recognised thresholds when placing slings underneath heavier patients. Raising the bed to at least knuckle level helps mitigate these spinal loads. PMID- 27400732 TI - Characterisation and comparison of adipose tissue macrophages from human subcutaneous, visceral and perivascular adipose tissue. AB - BACKGROUND AND AIMS: Macrophages play important roles in adipose tissue inflammation and its consequences. Unfortunately, a detailed description of the macrophage phenotypes in different human adipose tissues is not available. SUBJECTS AND METHODS: Subcutaneous, visceral and perivascular adipose tissues were obtained from 52 living kidney donors during live donor nephrectomy. Stromal vascular fractions were isolated, and the macrophage phenotypes were analyzed by flow cytometry using surface markers (CD14, CD16, CD36, and CD163). RESULTS: In addition to CD16 positivity, pro-inflammatory macrophages also display high scavenger receptor CD36 expression. The great majority of CD16 negative macrophages express the anti-inflammatory CD163 marker. The presence of pro inflammatory macrophages was almost twice as high in visceral (p < 0.0001) and perivascular (p < 0.0001) adipose tissues than in subcutaneous tissue. This difference was substantially more pronounced in the postmenopausal women subgroup, consequentlly, the total difference was driven by this subgroup. CONCLUSION: We obtained detailed information about M1 and M2 macrophage phenotypes in human adipose tissue. The visceral and perivascular adipose tissues had substantially higher pro-inflammatory characteristics than the subcutaneous tissue. The higher proportion of pro-inflammatory macrophages in the visceral adipose tissue of postmenopausal women might be related to an increased cardiovascular risk. PMID- 27400733 TI - High-throughput sequencing of 16S rRNA Gene Reveals Substantial Bacterial Diversity on the Municipal Dumpsite. AB - BACKGROUND: Multiple types of solid waste in developing countries is disposed of together in dumpsites where there is interaction between humans, animals and the bacteria in the waste. To study the bacteria at the dumpsite and the associated risks, previous studies have focused on culturable, leaving behind a great number of unculturable bacteria. This study focuses on a more comprehensive approach to study bacteria at the dumpsite. Since the site comprised of unsorted wastes, a qualitative survey was first performed to identify the variety of solid waste as this has influence on the microbial composition. Thus, domestic (Dom), biomedical (Biom), river sludge (Riv), and fecal material of pigs scavenging on the dumpsite (FecD) were sampled. Total DNA was extracted from 78 samples and the v4-16S rRNA amplicons was characterized using an Illumina MiSeq platform. RESULTS: A total of 8,469,294 sequences passed quality control. Catchall analysis predicted a mean of 8243 species per sample. Diversity was high with an average InvSimpson index of 44.21 +/- 1.44. A total of 35 phyla were detected and the predominant were Firmicutes (38 %), Proteobacteria (35 %), Bacteroidetes (13 %) and Actinobacteria (3 %). Overall 76,862 OTUs were detected, however, only 20 % were found more than 10 times. The predominant OTUs were Acinetobacter (12.1 %), Clostridium sensu stricto (4.8 %), Proteinclasticum and Lactobacillus both at (3.4 %), Enterococcus (2.9 %) and Escherichia/Shigella (1.7 %). Indicator analysis (P <= 0.05, indicator value >= 70) shows that Halomonas, Idiomarina, Tisierella and Proteiniclasticum were associated with Biom; Enterococcus, Bifidobacteria, and Clostridium sensu stricto with FecD and Flavobacteria, Lysobacter and Commamonas to Riv. Acinetobacter and Clostridium sensu stricto were found in 62 % and 49 % of all samples, respectively, at the relative abundance of 1 %. None of OTUs was found across all samples. CONCLUSIONS: This study provides a comprehensive report on the abundance and diversity bacteria in municipal dumpsite. The species richness reported here shows the complexity of this man-made ecosystem and calls for further research to assess for a link between human diseases and the dumpsite. This would provide insight into proper disposal of the waste, as well as, limit the risks to human health associated with the dumpsite. PMID- 27400735 TI - Development of a Simple Adjustable Zinc Acid/Base Hybrid Catalyst for C-C and C-O Bond-Forming and C-C Bond-Cleavage Reactions. AB - A newly designed zinc Lewis acid/base hybrid catalyst was developed. By adjusting the Lewis acidity of the zinc center, aldol-type additions of 2-picolylamine Schiff base to aldehydes proceeded smoothly to afford syn-aldol adduct equivalents, trans-N,O-acetal adducts, in high yields with high selectivities. NMR experiments, including microchanneled cell for synthesis monitoring (MICCS) NMR analysis, revealed that anti-aldol adducts were formed at the initial stage of the reactions under kinetic control, but the final products were the trans (syn)-N,O-acetal adducts that were produced through a retro-aldol process under thermodynamic control. In the whole reaction process, the zinc catalyst played three important roles: i) promotion of the aldol process (C-C bond formation), ii) cyclization process to the N,O-acetal product (C-O bond formation), and iii) retro-aldol process from the anti-aldol adduct to the syn-aldol adduct (C-C bond cleavage and C-C bond formation). PMID- 27400734 TI - Erlotinib plus gemcitabine versus gemcitabine for pancreatic cancer: real-world analysis of Korean national database. AB - BACKGROUND: A randomized clinical trial has found that the addition of erlotinib to gemcitabine (GEM-E) for pancreatic cancer led to a modest increase in survival. The aim of this national population-based retrospective study was to compare the effectiveness of GEM-E to GEM alone for pancreatic cancer patients in real clinical practice. METHODS: Patients with pancreatic cancer (ICD-10: C25) with prescription claims of gemcitabine or erlotinib between Jan 1, 2007 and Dec 31, 2012 were retrospectively identified from the Korean Health Insurance claims database. To be included in the study population, patients were required to have had a histological or cytological diagnosis within one year before chemotherapy. Patients treated with prior radiotherapy, surgery, or chemotherapy were excluded to reduce heterogeneity. Overall survival from the initiation of therapy and the medical costs of GEM-E and GEM were compared. RESULTS: A total of 4,267 patients were included in the analysis. Overall survival was not significantly longer in patients treated with GEM-E (median 6.77 months for GEM-E vs. 6.68 months for GEM, p = 0.0977). There was also no significant difference in the respective one year survival rates (27.0 % vs. 27.3 %; p = 0.5988). Multivariate analysis using age, gender, and comorbidities as covariates did not reveal any significant differences in survival. Based on this relative effectiveness, the incremental cost per life year gained over GEM was estimated at USD 70,843.64 for GEM-E. CONCLUSIONS: GEM-E for pancreatic cancer is not more effective than GEM in a real world setting, and it does not provide reasonable cost-effectiveness over GEM. PMID- 27400736 TI - Regulating levels of the neuromodulator d-serine in human brain: structural insight into pLG72 and d-amino acid oxidase interaction. AB - The human flavoenzyme d-amino acid oxidase (hDAAO) degrades the NMDA-receptor modulator d-serine in the brain. Although hDAAO has been extensively characterized, little is known about its main modulator pLG72, a small protein encoded by the primate-specific gene G72 that has been associated with schizophrenia susceptibility. pLG72 interacts with neosynthesized hDAAO, promoting its inactivation and degradation. In this work, we used low-resolution techniques to characterize the surface topology of the hDAAO-pLG72 complex. By using limited proteolysis coupled to mass spectrometry, we could map the exposed regions in the two proteins after complex formation and highlighted an increased sensitivity to proteolysis of hDAAO in complex with pLG72. Cross-linking experiments by using bis(sulfosuccinimidyl)suberate identified the single covalent bond between T182 in hDAAO and K62 in pLG72. In order to validate the designed mode of interaction, three pLG72 variants incrementally truncated at the C terminus, in addition to a form lacking the 71 N-terminal residues, were produced. All variants were dimeric, folded, and interacted with hDAAO. The strongest decrease in affinity for hDAAO (as well as for the hydrophobic drug chlorpromazine) was apparent for the N-terminally deleted pLG72(72-153) form, which lacked K62. On the other hand, eliminating the disordered C-terminal tail yielded a more stable pLG72 protein, improved the binding to hDAAO, although giving lower enzyme inhibition. Elucidation of the mode of hDAAO-pLG72 interaction now makes it possible to design novel molecules that, by targeting the protein complex, can be therapeutically advantageous for diseases related to impairment in d-serine metabolism. PMID- 27400737 TI - Structural features of Cas2 from Thermococcus onnurineus in CRISPR-cas system type IV. AB - CRISPR-Cas is RNA-based prokaryotic immune systems that defend against exogenous genetic elements such as plasmids and viruses. Cas1 and Cas2 are highly conserved components that play an essential part in the adaptation stage of all CRISPR-Cas systems. Characterization of CRISPR-Cas genes in Thermococcus onnurineus reveals the association of the Cas2 gene with the putative type IV system that lacks Cas1 or its homologous genes. Here, we present a crystal structure of T. onnurineus Cas2 (Ton_Cas2) that exhibits a deep and wide cleft at an interface lined with positive residues (Arg16, Lys18, Lys19, Arg22, and Arg23). The obvious DNA recognizing loops in Cas2 from E. coli (Eco_Cas2) are absent in Ton_Cas2 and have significantly different shapes and electrostatic potential distributions around the putative nucleotide binding region. Furthermore, Ton_Cas2 lacks the hairpin motif at the C-terminus that is responsible for Cas1 binding in Eco_Cas2. These structural features could be a unique signature and indicate an altered functional mechanism in the adaptation stage of Cas2 in type IV CRISPR-Cas systems. PMID- 27400738 TI - Bariatric Surgery Induces White and Grey Matter Density Recovery in the Morbidly Obese: A Voxel-Based Morphometric Study. AB - Obesity is associated with lowered brain's grey (GM) and white matter (WM) density as measured by voxel-based morphometry (VBM). Nevertheless, it remains unknown whether obesity has a causal influence on cerebral atrophy. We recruited 47 morbidly obese subjects (mean BMI = 42.2, SD = 4.0, 42 females and five males) eligible for bariatric surgery and 29 non-obese subjects (mean BMI = 23.2, SD = 2.8, 23 females and six males) served as controls. Baseline scans were acquired with T1-weighted magnetic resonance imaging (MRI) at 1.5 Tesla; obese participants were scanned again six months after the surgery. Local GM and WM densities were quantified using VBM. Full-volume analyses were used for comparing baseline between-group differences as well as the effects of surgery-induced weight loss in the morbidly obese. Metabolic variables were used in linear models to predict WM and GM densities. Obese subjects had initially lower GM densities in widespread cortical areas including frontal, parietal, and temporal regions as well as insulae. Lower WM densities were observed throughout the WM. Bariatric surgery and concomitant weight loss resulted in global increase in WM density. Grey matter increase was limited to occipital and inferior temporal regions. Metabolic variables were associated with brain densities. We conclude that weight loss results in global recovery of WM as well as local recovery of grey matter densities. These changes likely reflect improved brain tissue integrity. Hum Brain Mapp 37:3745-3756, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400739 TI - Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I-NBOMe and 25I-NBOH. AB - The dimethoxyphenyl-N-((2-methoxyphenyl)methyl)ethanamine (NBOMe) compounds are potent serotonin 5-HT2A receptor agonists and have recently been subject to recreational use due to their hallucinogenic effects. Use of NBOMe compounds has been known since 2011, and several non-fatal and fatal intoxication cases have been reported in the scientific literature. The aim of this study was to determine the importance of the different cytochrome P450 enzymes (CYP) involved in the metabolism of 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2methoxybenzyl)ethanamine (25I-NBOMe) and 2-[[2-(4-iodo-2,5dimethoxyphenyl)ethylamino]methyl]phenol (25I NBOH) and to characterize the metabolites. The following approaches were used to identify the main enzymes involved in primary metabolism: incubation with a panel of CYP and monoamine oxidase (MAO) enzymes and incubation in pooled human liver microsomes (HLM) with and without specific CYP chemical inhibitors. The study was further substantiated by an evaluation of 25I-NBOMe and 25I-NBOH metabolism in single donor HLM. The metabolism pathways of 25I-NBOMe and 25I-NBOH were NADPHdependent with intrinsic clearance values of (CLint) of 70.1 and 118.7 mL/min/kg, respectively. The biotransformations included hydroxylation, O demethylation, N-dealkylation, dehydrogenation, and combinations thereof. The most abundant metabolites were all identified by retention time and spectrum matching with synthesized reference standards. The major CYP enzymes involved in the metabolism of 25I-NBOMe and 25INBOH were identified as CYP3A4 and CYP2D6, respectively. The compound 25I-NBOH was also liable to direct glucuronidation, which may diminish the impact of CYP2D6 genetic polymorphism. Users of 25I-NBOMe may be subject to drug-drug interactions (DDI) if 25I-NBOMe is taken with a strong CYP3A4 inhibitor. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27400740 TI - Practice related factors that may impact on postpartum care for mothers and infants in Australian general practice: a cross-sectional survey. AB - BACKGROUND: While there is a significant focus on the health and well-being of women during pregnancy, labour and birth, much less emphasis is placed on the care of postpartum women and their infants in primary care following the birth. Some studies have investigated the role of GPs in postpartum care, and others examined facilitators and barriers to mothers accessing care. However there is little information available to investigate the effect of practice related factors on access to care of mothers and infants at this time. METHODS: A 20-item questionnaire for completion by the practice managers was mailed to 497 general practices in Southern Queensland, Australia between February and July 2013. Questionnaire items included practice demographics, practice procedures and personnel including appointment scheduling, billing, practice nurse function and qualifications and a free-text option for comments. Descriptive statistics are presented as numbers and percentages. Chi Squared test compared practice location with methods of identification of postpartum women, practice size with other Queensland data and ANOVA compared practice size with the number of postpartum appointments. Logistic regression was used to predict variables that were related to booked appointment times. Free text responses were grouped in common themes. RESULTS: The response rate was 27.4 %. At 67.2 % of the practices, mothers had to self-identify as needing a postpartum consultation and most consultations were allocated 15 minutes or less. Only 20 % of practices accepted the government insurance payment (bulk-billing) for all maternal and infant services, with more practices bulk-billing children only. Out-of-pocket expenses ranged from $10-$60. Nearly 80 % of practice nurses saw postpartum mothers or infants 'nearly always' or 'sometimes'. Approximately 30 % had midwifery or child health training. There were higher odds of longer booked appointment times for solo practitioner practices (unadj OR 3.30 95%CI 1.03-10.57), but no other variables predicted booked appointment times CONCLUSIONS: This study identified a number of practice related factors that, if addressed, could positively impact on postpartum care. These include ensuring ongoing practice relationships to assist with booking appropriate consultation times and guaranteeing that there are no financial impediments to women accessing care. Some factors can easily be adapted within practices. Others would require changes of policy at a local or national level. PMID- 27400741 TI - Overweight at four years of age in a Swedish birth cohort: influence of neighbourhood-level purchasing power. AB - BACKGROUND: A number of child/parental factors have been shown to be significant predictors of childhood overweight, although a better understanding of possible contextual influences of neighbourhood-level characteristics might provide new insights leading to tailored, targeted interventions. The aim of this study was to explore the impact of neighbourhood purchasing power and its relationship with other known risk factors related to childhood overweight in a prospective birth cohort. METHODS: A prospective, population-based, birth-cohort study was conducted in south-western Sweden, comprising 2,666 infants born in 2007-2008. Childhood overweight was assessed by body mass index (BMI) data from follow-up examinations at four years of age (n = 2,026) and overweight defined according to the International Obesity Task Force. Using logistic regression analysis, the influential child/parental predictors were identified from the candidate predictors, viz. child's gender, as well as birth weight adjusted for gestational age and parental factors at recruitment, including maternal smoking status, maternal BMI (before pregnancy), paternal BMI and parental educational level. The children's residential parishes at follow-up were stratified by parish-level household purchasing power (<10 %, 10-19.9 %, 20-29.9 % and >=30 % of all resident families with low purchasing power) and the "contextual" influence was analysed. In each such neighbourhood stratum, the adjusted overweight ratio (AOR), i.e. the ratio between the observed number of overweight children and the expected number, taking account of the influential child/parental predictors, was estimated. RESULTS: The prevalence of overweight at four years of age was 11.9 %. In the economically strongest neighbourhoods (i.e. <10 % of resident families with low purchasing power), the AOR was 0.60 (95 % confidence interval (CI): 0.34 0.98). The corresponding empirically Bayes-adjusted AOR was 0.73 (95 % CI: 0.46 1.02; 97 % posterior probability of AOR <1). In the other neighbourhood strata, the statistical evidence of a deviant AOR was weaker. CONCLUSION: The economically strongest neighbourhoods had a lower prevalence than expected of overweight at four years of age. This finding should prompt studies to acquire more knowledge of potentially modifiable factors that differ between neighbourhoods and are related to childhood overweight, providing a basis for tailored, targeted interventions. PMID- 27400743 TI - Influence of apical enlargement and complementary canal preparation with the Self Adjusting File on endotoxin reduction in retreatment cases. AB - AIM: To compare the effectiveness of large apical preparations and complementary canal preparation with the Self-Adjusting File (SAF) in removing endotoxins from the root canal of teeth with apical periodontitis. METHODOLOGY: Ten single-rooted and single-canaled teeth with post-treatment apical periodontitis were selected. Endotoxin samples were taken after removal of the root filling (S1), after chemomechanical preparation (CMP) using 2.5% NaOCl and an R25 file (S2), after CMP using 2.5% NaOCl and an R40 file (S3) and after complementary CMP using the SAF system (S4). Limulus amebocyte lysate (LAL) was used to measure endotoxin levels. The Friedman and Wilcoxon tests were used to compare endotoxin levels at each clinical intervention (P < 0.05). RESULTS: After root filling removal, endotoxin was detected in 100% of the root canals (S1, 4.84 EU mL-1 ). CMP with the R25 file was able to significantly reduce endotoxin levels (P < 0.05). Increased levels of endotoxin removal were achieved by apical preparation with the R40 file (P < 0.05). Complementary CMP with SAF did not significantly reduce endotoxin levels (P > 0.05) following the use of the R40 instrument. CONCLUSIONS: Apical enlargement protocols were effective in significantly reducing endotoxin levels. Complementary preparation with the SAF system failed to eliminate residual endotoxin contents beyond those obtained with the R40 instrument. PMID- 27400742 TI - Use of complementary and alternative medicines in haemodialysis patients: a cross sectional study from Palestine. AB - BACKGROUND: Complementary and alternative medicine (CAM), and herbal therapies, are accepted worldwide, and have been important from medical, sociological and economic perspectives, among haemodialysis (HD) patients. The primary aim of this study was to evaluate the use of CAM among patients with end-stage renal disease (ESRD) who are undergoing HD. METHODS: Face-to-face interviews of patients with ESRD undergoing HD from ten outpatient renal departments at a national level in Palestine were conducted from June 2014 to January 2015. A survey questionnaire, which included questions on socio-demographic and clinical characteristics, and on the CAM therapies that were used, was administered. RESULTS: Out of 267 patients interviewed, 172 patients used at least one type of CAM in the last month prior to the interview, and thus the utilisation rate was 64.4 %. Forty one (15.4 %) patients reported using one type of CAMs, while 18.7 % used two different CAMs and 30.3 % used more than two types of CAMs for their health status. Of the patients who used CAM, herbal therapies were used most often (43.5 %), followed by honey (35.6 %), diet (22.8 %), and exorcism in Islam (16.9 %). The herbal therapies mentioned most often were Nigella sativa L. (18.7 %), followed by Salvia officinalis L. (16.9 %), and Pimpinella anisum L. (10.5 %). CONCLUSIONS: In conclusion, the prevalence of CAM is relatively high in the selected population. Most patients used biological therapies such as herbal remedies, thus highlighting a greater need for patient education regarding CAM therapies and possible herb-drug interactions. Health care providers must be aware of the potential benefits and risks related to CAM use. There is a need for more clinical research pertaining to CAM to reach stronger evidence regarding potential benefits and risks related to CAM use. PMID- 27400744 TI - Differences in quality of life in home-dwelling persons and nursing home residents with dementia - a cross-sectional study. AB - BACKGROUND: Dementia often eventually leads to dependency on others and finally to residential care. However, in Norway about half of the dementia population lives at home, due to individual and political wishes. There is scarce and inconclusive knowledge of how living in a nursing home differs from living at home for persons with dementia (PWDs) with regard to their quality of life (QoL). The first aim of the study was therefore to compare QoL, cognitive and physical functions, social contacts, sleep patterns, physical activity levels, exposure to light, and medication of PWDs in nursing homes and home-dwelling PWDs, and whether living in nursing homes was associated with a lower QoL than living at home for PWDs. A second aim was to examine if possible differences between residencies in QoL were consistent over time. METHODS: The cross-sectional study was based on baseline data from two RCT studies of PWDs. A total of 15 nursing homes with adapted units for PWDs and 23 adapted day care centres for home dwelling PWDs recruited 78 and 115 participants respectively. Trained nurses scored sociodemographic data, level of dementia (on the Clinical Dementia Rating scale), amount of medication, and QoL (QUALID). Sleep patterns, physical activity levels, and light exposure were measured by actigraphy. A multiple regression analysis was used to test the association between residency and QoL. The association between residency and change in QoL over time was investigated by linear regression analysis of a subsample with follow-up data. RESULTS: Home dwelling PWDs showed significantly higher QoL than PWDs in nursing homes. This difference was maintained even after stratifying on the severity of dementia. Home-dwelling PWDs with moderate dementia showed significantly less use of walking aids, more social contact, higher levels of activity and exposure to daylight, and less use of psychotropic medications. The regression model explained 28 % of the variance in QoL in persons with moderate dementia. However, only residency contributed significantly in the model. Residency also significantly predicted negative change over time in QoL. CONCLUSION: The study indicated that living at home as long as possible is not only desirable for economic or health political reasons but also is associated with higher QoL for persons with moderate dementia. More studies are needed to investigate how QoL could be increased for PWDs in nursing homes. PMID- 27400745 TI - Suicidal ideation in adolescents and their caregivers: a cross sectional survey in Japan. AB - BACKGROUNDS: Suicide is a leading cause of death in adolescence. Effective strategies are required to prevent suicide. We aimed to assess the prevalence of suicidal ideation in early teens and the relationship between family mental health and suicidal ideation of their child. METHODS: A population-based survey in a rural town included 185 junior high school students and their caregivers. Suicidal ideation and mental states were assessed with General Health Questionnaire (GHQ) and Profile of Mood States (POMS) form. RESULTS: Nineteen (10.3 %) students experienced suicidal ideation in the preceding weeks and had more mental health problems than students without suicidal ideation. Caregivers of students with suicidal ideation demonstrated significantly higher suicidal depression scores in GHQ. Multivariate logistic regression analysis revealed that suicidal depression of caregivers was the most important factor for suicidal ideation of students. CONCLUSIONS: Suicidal ideation of children is associated with suicidal depression of their caregivers. For the prevention of suicide in adolescents, not only their own mental status but also that of caregivers should be taken into consideration. PMID- 27400747 TI - Silver ions eluted from partially protected silver nanoparticles. AB - The most prominent character of a new type of antibacterial urological catheters is the zebra-stripe pattern of a silver film, which is plated electroless on their interior wall and capped by a very thin semipermeable layer of parylene. This design effectively controls the release rate of Ag(+) ions in artificial urine, which has been measured as function of time with optical emission spectroscopy. By evaluating the minimum inhibitory concentration against certain strains of bacteria with solutions of AgNO3 of known concentration with the method of optical density and applying this analysis to the silver-eluting catheters, it was shown that this moderation prolongs the period of their application significantly. But to act as antibacterial agent in chlorine containing solutions, as in urine, the presence of urea is required to avoid precipitation of AgCl and to meet or even exceed the minimum inhibitory concentration of Ag(+). The quality of the silver depot layer was further determined by the deposition rate and its morphology, which revealed that the film consisted of grains with a mean size of 150 nm. PMID- 27400748 TI - LRP1 expression in microglia is protective during CNS autoimmunity. AB - Multiple sclerosis is a devastating neurological disorder characterized by the autoimmune destruction of the central nervous system myelin. While T cells are known orchestrators of the immune response leading to MS pathology, the precise contribution of CNS resident and peripheral infiltrating myeloid cells is less well described. Here, we explore the myeloid cell function of Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor involved in myelin clearance and the inflammatory response, in the context of Multiple sclerosis. Supporting its central role in Multiple sclerosis pathology, we find that LRP1 expression is increased in Multiple sclerosis lesions in comparison to the surrounding healthy tissue. Using two genetic mouse models, we show that deletion of LRP1 in microglia, but not in peripheral macrophages, negatively impacts the progression of experimental autoimmune encephalomyelitis, an animal model of Multiple sclerosis. We further show that the increased disease severity in experimental autoimmune encephalomyelitis is not due to haplodeficiency of the Cx3cr1 locus. At the cellular level, microglia lacking LRP1 adopt a pro inflammatory phenotype characterized by amoeboid morphology and increased production of the inflammatory mediator TNF-alpha. We also show that LRP1 functions as a robust inhibitor of NF-kB activation in myeloid cells via a MyD88 dependent pathway, potentially explaining the increase in disease severity observed in mice lacking LRP1 expression in microglia. Taken together, our data suggest that the function of LRP1 in microglia is to keep these cells in an anti inflammatory and neuroprotective status during inflammatory insult, including experimental autoimmune encephalomyelitis and potentially in Multiple sclerosis. PMID- 27400749 TI - Invariant asymmetry renews the lymphatic vasculature during homeostasis. AB - BACKGROUND: The lymphatic vasculature regulates tissue physiology and immunity throughout life. The self renewal mechanism that maintains the lymphatic vasculature during conditions of homeostasis is unknown. The purpose of this study was to investigate the cellular mechanism of lymphatic endothelial cell (LEC) self renewal and lymphatic vessel maintenance. METHODS: Inductive genetic techniques were used to label LECs with tandem dimer tomato (tdT) in adult mice. Two types of studies were performed, those with high dose inductive conditions to label nearly all the lymphatic vessels and studies with low dose inductive conditions to stochastically label individual clones or small populations of LECs. We coupled image guidance techniques and live fluorescence microscopy imaging with lineage tracing to track the fate of entire tdT(+) cutaneous lymphatic vessels or the behavior of individual or small populations of LECs over 11 months. We tracked the fate of 110 LEC clones and 80 small LEC populations (clusters of 2-7 cells) over 11 months and analyzed their behavior using quantitative techniques. RESULTS: The results of the high dose inductive studies showed that the lymphatic vessels remained tdT(+) over 11 months, suggesting passage and expression of the tdT transgene from LEC precursors to progenies, an intrinsic model of self- renewal. Interestingly, the morphology of tdT(+) lymphatic vasculature appeared relatively stable without significant remodeling during this time period. By following the behavior of labeled LEC clones or small populations of LECs individually over 11 months, we identified diverse LEC fates of proliferation, quiescence, and extinction. Quantitative analysis of this data revealed that the average lymphatic endothelial clone or small population remained stable in size despite diverse individual fates. CONCLUSION: The results of these studies support a mechanism of invariant asymmetry to self renew the lymphatic vasculature during homeostasis. These original findings raise important questions related to the plasticity and self renewal properties that maintain the lymphatic vasculature during life. PMID- 27400746 TI - Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. AB - Alzheimer's disease (AD) is an incurable and debilitating chronic progressive neurodegenerative disorder which is the leading cause of dementia worldwide. AD is a heterogeneous and multifactorial disorder, histopathologically characterized by the presence of amyloid beta (Abeta) plaques and neurofibrillary tangles composed of Abeta peptides and abnormally hyperphosphorylated tau protein, respectively. Independent of the various etiopathogenic mechanisms, neurodegeneration is a final common outcome of AD neuropathology. Synaptic loss is a better correlate of cognitive impairment in AD than Abeta or tau pathologies. Thus a highly promising therapeutic strategy for AD is to shift the balance from neurodegeneration to neuroregeneration and synaptic repair. Neurotrophic factors, by virtue of their neurogenic and neurotrophic activities, have potential for the treatment of AD. However, the clinical therapeutic usage of recombinant neurotrophic factors is limited because of the insurmountable hurdles of unfavorable pharmacokinetic properties, poor blood-brain barrier (BBB) permeability, and severe adverse effects. Neurotrophic factor small-molecule mimetics, in this context, represent a potential strategy to overcome these short comings, and have shown promise in preclinical studies. Neurotrophic factor small molecule mimetics have been the focus of intense research in recent years for AD drug development. Here, we review the relevant literature regarding the therapeutic beneficial effect of neurotrophic factors in AD, and then discuss the recent status of research regarding the neurotrophic factor small-molecule mimetics as therapeutic candidates for AD. Lastly, we summarize the preclinical studies with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021). P021 is a neurogenic and neurotrophic compound which enhances dentate gyrus neurogenesis and memory processes via inhibiting leukemia inhibitory factor (LIF) signaling pathway and increasing brain-derived neurotrophic factor (BDNF) expression. It robustly inhibits tau abnormal hyperphosphorylation via increased BDNF mediated decrease in glycogen synthase kinase-3beta (GSK-3beta, major tau kinase) activity. P021 is a small molecular weight, BBB permeable compound with suitable pharmacokinetics for oral administration, and without adverse effects associated with native CNTF or BDNF molecule. P021 has shown beneficial therapeutic effect in several preclinical studies and has emerged as a highly promising compound for AD drug development. PMID- 27400752 TI - Causality evaluation of bacterial species isolated from patients with community acquired lower leg cellulitis. AB - INTRODUCTION: Lower leg cellulitis is a diffuse inflammation of the cutaneous connective tissue following invasion of microorganisms and with potential to recur. The causative agent is not routinely identified in clinical practice, and the empirical therapy initiated primarily targets the 'conventional' disease pathogens, Streptococcus pyogenes and Staphylococcus aureus. OBJECTIVE: To evaluate at case level, the role of bacterial species isolated from lesional skin in the pathogenesis of community-acquired lower leg cellulitis. METHODS: Two sampling methods (superficial swab and biopsy) were applied to isolate bacterial species from 40 patients hospitalized for first (N = 24 cases) and recurrent (N = 16 patients) lower leg cellulitis episodes. Subsequently, a clinical-laboratory heuristic algorithm was employed to interpret causality associations of isolated species with disease episodes at case level. RESULTS: In 37/40 cases (92.5%), at least one bacterial species was identified with either sampling method. The number of different species/specimen isolated from superficial swabs compared to punch biopsies was significantly more (P < 0.001). A causative agent was identified in 16 cases (40%); it was a 'conventional' pathogen in seven patients and strains belonging to one of six 'non-conventional' pathogens in nine cases. There was no concordance in the spectrum of isolated pathogens with the two sampling methods (kappa-index = 0.028). Another four species may have participated in five patients as co-pathogens in mixed infections. There was also no difference in microbiological disease features between patients with first and recurrent cellulitis episodes. CONCLUSIONS: The application of a clinical laboratory causality algorithm coupled with pooled culture results of more than one sampling methods in patients with lower leg cellulitis is anticipated to permit the identification of responsible bacterial species at case level and offer incentive for therapeutic intervention studies. PMID- 27400750 TI - Genotypic and phenotypic relatedness of Pseudomonas aeruginosa isolates among the major cystic fibrosis patient cohort in Italy. AB - BACKGROUND: Pseudomonas aeruginosa is the predominant pathogen associated with the decline of pulmonary function in cystic fibrosis (CF) patients. Both environment-to-host acquisition and patient-to-patient transmission have been described for P. aeruginosa infection. Epidemic clones and bacterial phenotypic adaptation to the CF lung have been recognised as independent risk factors for disease progression. So far, there is no established link between genotypic prevalence and phenotypic traits. Here, we look at the major CF patient cohort in Italy to identify shared P. aeruginosa clones and associated common phenotypic traits. RESULTS: A comprehensive analysis of P. aeruginosa genotypes to determine the presence of high-risk shared clones and their association to specific phenotypic traits has been performed in a major Italian CF centre. Pulsed-field gel electrophoresis (PFGE) of P. aeruginosa isolates from 338 CF subjects identified 43 profiles shared by two or more patients and 214 profiles exclusive to individual patients. There was no evidence of a P. aeruginosa outbreak, but four most prevalent pulsotypes were detected. Common phenotypic traits were recorded intra-pulsotypes, but we detected heterogeneity inter-pulsotypes. Two of the four major pulsotypes included P. aeruginosa isolates with hallmarks of adaptation to the CF airways, including loss of motility, low production of siderophore, pyocyanin and proteases, and antibiotic resistance. One of these pulsotypes grouped a high percentage of hypermutable isolates. No clear correlation between epidemiological and clinical data was found. CONCLUSIONS: We conclude that CF patients of this cohort shared common pulsotypes, but their phenotypic heterogeneity indicates an absence of specific traits associated to P. aeruginosa genotypic prevalence. PMID- 27400751 TI - Osteopontin splice variants are differential predictors of breast cancer treatment responses. AB - BACKGROUND: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. METHODS: Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. RESULTS: We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. CONCLUSIONS: The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment. PMID- 27400754 TI - Unemployment Risk and Decreased Income Two and Four Years After Thyroid Cancer Diagnosis: A Population-Based Study. AB - BACKGROUND: Thyroid cancer (TC) often occurs in relatively young patients and has a high cure rate. However, decreased psychological and physical well-being may reduce the work capability of patients with TC. This study aimed to compare the risk for unemployment and decreased income in TC survivors with a matched non cancer group at two and four years after diagnosis. The study also aimed to predict unemployment and income changes at two and four years after diagnosis. METHODS: A historical prospective study design was used, with cohort inception and baseline measurements drawn from the Israeli Central Bureau of Statistics 1995 National Census, with follow-up until 2011. Cancer incidence was obtained from the Israel Cancer Registry, and employment status from the Tax Authority. A matched group was sampled from the census population. Binary logistic regression analyses were used to assess odds ratios (OR) for the study outcomes, controlled for age, sex, ethnicity, education years, socioeconomic position, and employment status at two years before diagnosis. RESULTS: In total, 417 cases of TC and 1277 non-cancer matched subjects were included in the study. People who died during the study period were excluded. The mean age at the time of cancer diagnosis was 43.5 years in the TC group and 43.8 years in the control group (p = 0.6). After adjusting for potential confounders, a positive association was found between TC and risk of unemployment two years after diagnosis (OR = 1.46 [confidence interval (CI) 1.09-1.95]), and decreased income two years after diagnosis (OR = 1.61 [CI 1.23-2.01]) and four years after diagnosis (OR = 1.63 [CI 1.25-2.13]). The association between TC and unemployment at four years after diagnosis weakened and lost significance (OR = 1.30 [CI 0.98-1.72]). CONCLUSIONS: TC survivorship was associated with unemployment at two years and decreased income at two and four years after diagnosis. Decreased income may be a marker for a shift to part-time work rather than a return to full-time work. The findings suggest that interventions to enhance the return to full-time work are needed in this population. PMID- 27400753 TI - Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia. AB - The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low-risk karyotype (P < .001), no high-risk karyotype (P = .006), positivity for AML-ETO (P = .004)/CBFbeta-MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3-ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 * 109 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 * 109 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported. PMID- 27400755 TI - Paediatric recreational vehicle-related head injuries presenting to the emergency department of a major paediatric trauma centre in Australia: Is there room for improvement? AB - OBJECTIVE: This study examines clinical characteristics and helmet use of children presenting to the ED with a recreational vehicle (RV)-related head injury (HI). METHODS: Observational retrospective study of children <18 years presenting with a RV-related HI to the ED of a state-wide paediatric trauma centre in Australia between April 2011 and January 2014. RESULTS: In the 647 presentations identified, corresponding to 7.5% (95% CI 7.0-8.1) of all HI presentations, RVs involved were bicycles (36.3%), push scooters (18.5%), motorcycles (18.4%), horses (11.7%), skateboards (11.6%), quadbikes (2.8%) and go karts (0.6%). Recorded helmet use was the highest in motorcycle, horse and bicycle riders (83.2%, 82.9% and 65.1%, respectively), and the lowest for push scooter (25.8%) and skateboard riders (17.3%). Overall 23% underwent a CT scan, 8.8% had intracranial injuries on CT, 30.6% were admitted, and 2.2% underwent neurosurgery. Push scooter-related HIs were the least severe. Age (in years), riding a motorised vehicle and not wearing a helmet were independently associated with intracranial injuries on CT on multiple logistic regression (OR 1.1, 95% CI 1.0-1.2; OR 2.4, 95% CI 1.3-4.6 and OR 6.0, 95% CI 3.2-11.2, respectively). CONCLUSIONS: RV-related HIs accounted for a non-negligible proportion of paediatric HIs presenting to the ED and for significant morbidity and use of hospital resources. Interventions such as introduction of mandatory helmet use for off-road motorised vehicle riding and skateboard riding in children, enhanced injury prevention campaigns, and strict adult supervision during motorised vehicle riding may reduce the morbidity and health care costs associated with paediatric RV-related HIs. PMID- 27400756 TI - Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry. AB - Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240 fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. PMID- 27400757 TI - Update in perioperative medicine: practice-changing evidence published in 2015. AB - Evidence in perioperative medicine is published in a wide variety of journals, given the multidisciplinary nature of its practice which spans medicine and its subspecialties, as well as surgery and anesthesiology. It can be difficult to identify new and important evidence, as perioperative practice continues to evolve in multiple areas such as medication management, anticoagulation and cardiac risk stratification, among others. New, high-quality evidence is published each year, and must be placed into the context of not only existing literature, but also practical real-world patient care. We sought to systematically identify, critically evaluate and concisely summarize the practice implications of 10 articles published in 2015 for the practicing perioperative clinician. PMID- 27400758 TI - Hierarchical MoO2/Mo2C/C Hybrid Nanowires as High-Rate and Long-Life Anodes for Lithium-Ion Batteries. AB - Hierarchical MoO2/Mo2C/C hybrid nanowires (MoO2/Mo2C/C HNWs) have been fabricated through facile calcination of Mo3O10(C6H5NH3)2.2H2O nanowires which serve as both precursors and self-templates. In the MoO2/Mo2C/C HNWs, nanoparticles dispersed in the nanowires are beneficial for Li(+) transportation due to the decreased diffusion paths. Moreover, hybridization with Mo2C and carbon facilitates the electron transfer and increases the structural stability without sacrifice of capacity. As anode materials for lithium-ion batteries, the MoO2/Mo2C/C HNWs exhibit a reversible capacity of 950 mA h g(-1) after 320 cycles at a current density of 200 mA g(-1). Even when cycled at 2000 mA g(-1), they maintained a reversible capacity of 602 mA h g(-1) after 500 cycles. By incorporation of Mo2C and C with MoO2, the MoO2/Mo2C/C HNWs show high-rate capability and long cycle life and can be a promising candidate for lithium-ion battery anodes. PMID- 27400759 TI - Poly(isophthalic acid)(ethylene oxide) as a Macromolecular Modulator for Metal Organic Polyhedra. AB - A new strategy was developed by using a polymer ligand, poly(isophthalic acid)(ethylene oxide), to modulate the growth of metal-organic polyhedra (MOP) crystals. This macromolecular modulator can effectively control the crystal habit of several different Cu24L24 (L = isophthalic acid derivatives) MOPs. The polymer also directed the formation of MOP structures under reaction conditions that only produce metal-organic frameworks in the absence of modulator. Moreover, the polymer also enabled the deposition of MOP crystals on glass surfaces. This macromolecular modulator strategy provides an innovative approach to control the morphology and assembly of MOP particles. PMID- 27400760 TI - Topography evolution of 500 keV Ar(4+) ion beam irradiated InP(100) surfaces - formation of self-organized In-rich nano-dots and scaling laws. AB - We report the formation of self-organized nano-dots on the surface of InP(100) upon irradiating it with a 500 keV Ar(4+) ion beam. The irradiation was carried out at an angle of 25 degrees with respect to the normal at the surface with 5 different fluences ranging from 1.0 * 10(15) to 1.0 * 10(17) ions per cm(2). The morphology of the ion-irradiated surfaces was examined by atomic force microscopy (AFM) and the formation of the nano-dots on the irradiated surfaces was confirmed. The average size of the nano-dots varied from 44 +/- 14 nm to 94 +/- 26 nm with increasing ion fluence. As a function of the ion fluence, the variation in the average size of the nano-dots has a great correlation with the surface roughness, which changes drastically up to the ion fluence of 1.0 * 10(16) ions per cm(2) and attains almost a saturation level for further irradiation. The roughness and the growth exponent values deduced from the scaling laws suggest that the kinetic sputtering and the large surface diffusion steps of the atoms are the primary reasons for the formation of the self organized nanodots on the surface. X-ray photo-electron spectroscopy (XPS) studies show that the surface stoichiometry changes with the ion fluence. With irradiation, the surface becomes more indium (In)-rich owing to the preferential sputtering of the phosphorus atoms (P) and the pure metallic In nano-dots evolve at the highest ion fluence. The cross-sectional scanning electron microscopy (SEM) analysis of the sample irradiated with the highest fluence showed the absence of the nanostructuring beneath the surface. The surface morphological changes at this medium energy ion irradiation are discussed in correlation with the low and high energy experiments to shed more light on the mechanism of the well separated nano-dot formation. PMID- 27400761 TI - Korean Version of the painDETECT Questionnaire: A Study for Cultural Adaptation and Validation. AB - OBJECTIVE: The purpose of this study was to adapt the painDETECT Questionnaire (PD-Q) into a Korean version (KPD-Q) and validate it. METHODS: A single-center prospective observational study was performed. During the first phase of the study, linguistic adaptation was carried out to develop the KPD-Q. During the second phase of the study, feasibility, internal consistency, discriminant validity, and concurrent validity were assessed for psychometric validation of the KPD-Q. RESULTS: A total of 232 patients participated. Among them, 82 patients (35%) were classified in the neuropathic pain (NeP) group, 80 (34%) in the nociceptive pain group, and 70 (30%) in the mixed pain group. Regarding the reliability of the KPD-Q, internal consistency for the whole scale was 0.804, as evaluated by Cronbach's alpha. Pearson's correlation between the Leeds Assessment of Neuropathic Symptoms and Signs scale and the KPD-Q scores was positive and statistically significant (r = 0.74, P < 0.001). Similar to the result obtained by the original developers, a value of >= 19 points suggested a clear diagnosis of the presence of an NeP component with 95.4% sensitivity, 73.8% specificity, and 0.737 Youden index. We used <= 13 (as opposed to <= 12, as suggested previously) as an alternative cutoff value, which showed a sensitivity of 95.4%, specificity of 73.8%, and the Youden index of 0.691. CONCLUSION: The KPD-Q showed good psychometric and discriminant features for assessing the neuropathic component in chronic pain patients. We hope that this newly validated KPD-Q will be recognized in Korea as a credible tool for detection of NeP and thus may be used in further international clinical research. PMID- 27400762 TI - The growth of vegetative and reproductive structures (leaves and silks) respond similarly to hydraulic cues in maize. AB - The elongation of styles and stigma (silks) of maize (Zea mays) flowers is rapid (1-3 mm h(-1) ), occurs over a short period and plays a pivotal role in reproductive success in adverse environments. Silk elongation rate was measured using displacement transducers in 350 plants of eight genotypes during eight experiments with varying evaporative demand and soil water status. Measured time courses revealed that silk elongation rate closely followed changes in soil water status and evaporative demand, with day-night alternations similar to those in leaves. Day-night alternations were steeper with high than with low plant transpiration rate, manipulated via evaporative demand or by covering part of the leaf area. Half times of changes in silk elongation rate upon changes in evaporative demand or soil water status were 10-30 min, similar to those in leaves. The sensitivity of silk elongation rate to xylem water potential was genetically linked to that of leaf elongation rate. Lines greatly differed for these sensitivities. These results are consistent with a common hydraulic control of expansive growth in vegetative and reproductive structures upon changes in environmental conditions via a close connection with the xylem water potential. They have important implications for breeding, modelling and phenotyping. PMID- 27400763 TI - Innovations in deep brain stimulation methodology. AB - Deep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near-term clinical application. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27400764 TI - Predicting Risk of Suicide Attempt Using History of Physical Illnesses From Electronic Medical Records. AB - BACKGROUND: Although physical illnesses, routinely documented in electronic medical records (EMR), have been found to be a contributing factor to suicides, no automated systems use this information to predict suicide risk. OBJECTIVE: The aim of this study is to quantify the impact of physical illnesses on suicide risk, and develop a predictive model that captures this relationship using EMR data. METHODS: We used history of physical illnesses (except chapter V: Mental and behavioral disorders) from EMR data over different time-periods to build a lookup table that contains the probability of suicide risk for each chapter of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes. The lookup table was then used to predict the probability of suicide risk for any new assessment. Based on the different lengths of history of physical illnesses, we developed six different models to predict suicide risk. We tested the performance of developed models to predict 90 day risk using historical data over differing time-periods ranging from 3 to 48 months. A total of 16,858 assessments from 7399 mental health patients with at least one risk assessment was used for the validation of the developed model. The performance was measured using area under the receiver operating characteristic curve (AUC). RESULTS: The best predictive results were derived (AUC=0.71) using combined data across all time-periods, which significantly outperformed the clinical baseline derived from routine risk assessment (AUC=0.56). The proposed approach thus shows potential to be incorporated in the broader risk assessment processes used by clinicians. CONCLUSIONS: This study provides a novel approach to exploit the history of physical illnesses extracted from EMR (ICD-10 codes without chapter V-mental and behavioral disorders) to predict suicide risk, and this model outperforms existing clinical assessments of suicide risk. PMID- 27400766 TI - Rhodium(iii)-catalyzed alkylation of primary C(sp(3))-H bonds with alpha diazocarbonyl compounds. AB - Rh(iii)-catalyzed intermolecular chelation-assisted insertion of carbenes derived from alpha-diazocarbonyl compounds into non-acidic primary sp(3) C-H bonds, for the first time, is reported under mild reaction conditions, thus affording a good complement to previous metal-carbenoid-induced primary C(sp(3))-H insertion reactions. We believe that this method will open up a new avenue for primary sp(3) C-H functionalization with alpha-diazocarbonyl compounds. PMID- 27400765 TI - Using Patient-Specific Induced Pluripotent Stem Cells and Wild-Type Mice to Develop a Gene Augmentation-Based Strategy to Treat CLN3-Associated Retinal Degeneration. AB - Juvenile neuronal ceroid lipofuscinosis (JNCL) is a childhood neurodegenerative disease with early-onset, severe central vision loss. Affected children develop seizures and CNS degeneration accompanied by severe motor and cognitive deficits. There is no cure for JNCL, and patients usually die during the second or third decade of life. In this study, independent lines of induced pluripotent stem cells (iPSCs) were generated from two patients with molecularly confirmed mutations in CLN3, the gene mutated in JNCL. Clinical-grade adeno-associated adenovirus serotype 2 (AAV2) carrying the full-length coding sequence of human CLN3 was generated in a U.S. Food and Drug Administration-registered cGMP facility. AAV2-CLN3 was efficacious in restoring full-length CLN3 transcript and protein in patient-specific fibroblasts and iPSC-derived retinal neurons. When injected into the subretinal space of wild-type mice, purified AAV2-CLN3 did not show any evidence of retinal toxicity. This study provides proof-of-principle for initiation of a clinical trial using AAV-mediated gene augmentation for the treatment of children with CLN3-associated retinal degeneration. PMID- 27400767 TI - Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays. AB - The analysis of disease-specific biomarker panels holds promise for the early detection of a range of diseases, including cancer. Blood-based biomarkers, in particular, are attractive targets for minimally-invasive disease diagnosis. Specifically, a panel of organ-specific biomarkers could find utility as a general disease surveillance tool enabling earlier detection or prognostic monitoring. Using arrays of chip-integrated silicon photonic sensors, we describe the simultaneous detection of eight cancer biomarkers in serum in a relatively rapid (1 hour) and fully automated antibody-based sandwich assay. Biomarkers were chosen for their applicability to a range of organ-specific cancers, including disease of the pancreas, liver, ovary, breast, lung, colorectum, and prostate. Importantly, we demonstrate that selected patient samples reveal biomarker "fingerprints" that may be useful for a personalized cancer diagnosis. More generally, we show that the silicon photonic technology is capable of measuring multiplexed panels of protein biomarkers that may have broad utility in clinical diagnostics. PMID- 27400768 TI - Current developments to use linear MALDI-TOF spectra for the identification and typing of bacteria and the characterization of other cells/organisms related to infectious diseases. AB - Within the past few years identification of bacteria by MALDI-TOF MS has become a standard technique in bacteriological laboratories for good reasons. MALDI-TOF MS identification is rapid, robust, automatable, and the per-sample costs are low. Yet, the spectra are very informative and the reliable identification of bacterial species is usually possible. Recently, new MS-based approaches for the identification of bacteria are emerging that are based on the detailed analysis of the bacterial proteome by high-resolution MS. These "proteotyping" approaches are highly discriminative and outperform MALDI-TOF MS-based identification in terms of specificity, but require a laborious proteomic workflow and far more expertise and sophisticated instrumentation than identification on basis of MALDI TOF MS spectra, which can be obtained with relative simple and uncostly linear MALDI-TOF mass spectrometers. Thus MALDI-TOF MS identification of bacteria remains an attractive option for routine diagnostics. Additionally, MALDI-TOF MS identification protocols have been extended and improved in many respects making linear MALDI-TOF MS a versatile tool that can be useful beyond the identification of a bacterial species, e.g. for the characterization of leucocytes and arthropod vectors of infectious diseases. This review focuses on such improvements and extensions of the typical MALDI-TOF MS workflow in the field of infectious diseases. PMID- 27400769 TI - Interaction and localization diversities of global and local hubs in human protein-protein interaction networks. AB - Hubs, the highly connected nodes in protein-protein interaction networks (PPINs), are associated with several characteristic properties and are known to perform vital roles in cells. We defined two classes of hubs, global (housekeeping) and local (tissue-specific) hubs. These two categories of hubs are distinct from each other with respect to their abundance, structure and function. However, how distinct are the spatial expression pattern and other characteristics of their interacting partners is still not known. Our investigations revealed that the partners of the local hubs compared with those of global hubs are conserved across the tissues in which they are expressed. Partners of local hubs show diverse subcellular localizations as compared with the partners of global hubs. We examined the nature of interacting domains in both categories of hubs and found that they are promiscuous in global hubs but not so in local hubs. Deletion of some of the local and global hubs has an impact on the characteristic path length of the network indicating that those hubs are inter-modular in nature. Our present study has, therefore, shed further light on the characteristic features of the local and global hubs in human PPIN. This knowledge of different topological aspects of hubs with regard to their types and subtypes is essential as it helps in better understanding of roles of hub proteins in various cellular processes under various conditions including those caused by host-pathogen interactions and therefore useful in prioritizing targets for drug design and repositioning. PMID- 27400770 TI - Crystal structure and analysis of HdaB: The enteroaggregative Escherichia coli AAF/IV pilus tip protein. AB - Enteroaggregative Escherichia coli is the primary cause of pediatric diarrhea in developing countries. They utilize aggregative adherence fimbriae (AAFs) to promote initial adherence to the host intestinal mucosa, promote the formation of biofilms, and mediate host invasion. Five AAFs have been identified to date and AAF/IV is amongst the most prevalent found in clinical isolates. Here we present the X-ray crystal structure of the AAF/IV tip protein HdaB at 2.0 A resolution. It shares high structural homology with members of the Afa/Dr superfamily of fimbriae, which are involved in host invasion. We highlight surface exposed residues that share sequence homology and propose that these may function in invasion and also non-conserved regions that could mediate HdaB specific adhesive functions. PMID- 27400772 TI - Preserved white matter microstructure in young patients with anorexia nervosa? AB - A massive but reversible reduction of cortical thickness and subcortical gray matter (GM) volumes in Anorexia Nervosa (AN) has been recently reported. However, the literature on alterations in white matter (WM) volume and microstructure changes in both acutely underweight AN (acAN) and after recovery (recAN) is sparse and results are inconclusive. Here, T1-weighted and diffusion-weighted MRI data in a sizable sample of young and medication-free acAN (n = 35), recAN (n = 32), and age-matched female healthy controls (HC, n = 62) were obtained. For analysis, a well-validated global probabilistic tractography reconstruction algorithm including rigorous motion correction implemented in FreeSurfer: TRACULA (TRActs Constrained by UnderLying Anatomy) were used. Additionally, a clustering algorithm and a multivariate pattern classification technique to WM metrics to predict group membership were applied. No group differences in either WM volume or WM microstructure were detected with standard analysis procedures either in acAN or recAN relative to HC after controlling for the number of performed statistical tests. These findings were not affected by age, IQ, or psychiatric symptoms. While cluster analysis was unsuccessful at discriminating between groups, multivariate pattern classification showed some ability to separate acAN from HC (but not recAN from HC). However, these results were not compatible with a straightforward hypothesis of impaired WM microstructure. The current findings suggest that WM integrity is largely preserved in non-chronic AN. This finding stands in contrast to findings in GM, but may help to explain the relatively intact cognitive performance of young patients with AN and provide the basis for the fast recovery of GM structures. Hum Brain Mapp 37:4069-4083, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400773 TI - Quantification of synthetic cannabinoids in herbal smoking blends using NMR. AB - Herbal smoking blends containing synthetic cannabinoids have become popular alternatives to marijuana. These products were previously sold in pre-packaged foil bags, but nowadays seizures usually contain synthetic cannabinoid powders together with unprepared plant materials. A question often raised by the Swedish police is how much smoking blend can be prepared from certain amounts of banned substance, in order to establish the severity of the crime. To address this question, information about the synthetic cannabinoid content in both the powder and the prepared herbal blends is necessary. In this work, an extraction procedure compatible with direct NMR quantification of synthetic cannabinoids in herbal smoking blends was developed. Extraction media, time and efficiency were tested for different carrier materials containing representative synthetic cannabinoids. The developed protocol utilizes a 30 min extraction step in d4 methanol in presence of internal standard allowing direct quantitation of the extract using NMR. The accuracy of the developed method was tested using in-house prepared herbal smoking blends. The results showed deviations less than 0.2% from the actual content, proving that the method is sufficiently accurate for these quantifications. Using this method, ten synthetic cannabinoids present in sixty three different herbal blends seized by the Swedish police between October 2012 and April 2015 were quantified. Obtained results showed a variation in cannabinoid contents from 1.5% (w/w) for mixtures containing MDMB-CHMICA to over 5% (w/w) for mixtures containing 5F-AKB-48. This is important information for forensic experts when making theoretical calculations of production quantities in legal cases regarding "home-made" herbal smoking blends. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27400774 TI - Resection of asymptomatic primary tumour in unresectable stage IV colorectal cancer: time to move on from propensity matched scores to randomized controlled trials. PMID- 27400776 TI - Status of and problems concerning neonatal resuscitation in Japan in 2015. AB - BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) published Consensus 2015 in October 2015. Thereafter, the Japanese version of neonatal cardiopulmonary resuscitation programs was revised. Prior to the revision, we re-conducted questionnaire surveys in three types of medical facilities in January 2015. METHODS: Targeted groups included (i) 277 training hospitals authorized by the Japanese Society of Perinatal/Neonatal Medicine for training of physicians specialized in perinatal care (neonatology) in January 2015 (training hospitals; response rate, 70.8%); (ii) 459 obstetric hospitals/clinics (response rate, 63.6%); and (iii) 453 midwife clinics (response rate, 60.9%). The survey included systems of neonatal resuscitation, medical equipment and practices, and education systems. The results were compared with that of similar surveys conducted in 2005, 2010 and 2013. RESULTS: Almost all results were generally improved compared with past surveys. In training hospitals, however, the use of oxygen blenders or manometers was not widespread. Only 35% of institutions used continuous positive airway pressure systems frequently, and expert neonatal resuscitation doctors attended all deliveries in only 6% of training centers. In addition, only 71% of training hospitals had brain therapeutic hypothermia facilities. Not all obstetric hospitals/clinics prepared pulse oximeters, and only a few used manometers frequently. Some midwife clinics did not keep warming equipment, and few midwife clinics were equipped with pulse oximeters. In addition, some midwife clinics did not prepare ventilation bags (masks). CONCLUSIONS: The equipment in Japanese delivery rooms is variable. Further efforts need to be made in the distribution of neonatal resuscitation devices and the dissemination of techniques. PMID- 27400775 TI - Effects of a novel potent melanin-concentrating hormone receptor 1 antagonist, AZD1979, on body weight homeostasis in mice and dogs. AB - BACKGROUND AND PURPOSE: Melanin-concentrating hormone (MCH) is an orexigen, and while rodents express one MCH receptor (MCH1 receptor), humans, non-human primates and dogs express two MCH receptors (MCH1 and MCH2 ). MCH1 receptor antagonists have been developed for the treatment of obesity and lower body weight in rodents. However, the mechanisms for the body weight loss and whether MCH1 receptor antagonism can lower body weight in species expressing both MCH receptors are not fully understood. EXPERIMENTAL APPROACH: A novel recently identified potent MCH1 receptor antagonist, AZD1979, was studied in wild type and Mchr1 knockout (KO) mice and by using pair-feeding and indirect calorimetry in diet-induced obese (DIO) mice. The effect of AZD1979 on body weight was also studied in beagle dogs. KEY RESULTS: AZD1979 bound to MCH1 receptors in the CNS and dose-dependently reduced body weight in DIO mice leading to improved homeostasis model assessment-index of insulin sensitivity. AZD1979 did not affect food intake or body weight in Mchr1 KO mice demonstrating specificity for the MCH1 receptor mechanism. In DIO mice, initial AZD1979-mediated body weight loss was driven by decreased food intake, but an additional component of preserved energy expenditure was apparent in pair-feeding and indirect calorimetry studies. AZD1979 also dose-dependently reduced body weight in dogs. CONCLUSION AND IMPLICATIONS: AZD1979 is a novel potent MCH1 receptor antagonist that affects both food intake and energy expenditure. That AZD1979 also lowers body weight in a species expressing both MCH receptors holds promise for the use of MCH1 receptor antagonists for the treatment of human obesity. PMID- 27400777 TI - Unveil the Size-Dependent Mechanical Behaviors of Individual CNT/SiC Composite Nanofibers by In Situ Tensile Tests in SEM. AB - In situ quantitative tensile tests of individual carbon nanotube (CNT)/SiC core shell nanofibers are carried out in both a scanning electron microscope (SEM) and a transmission electron microscope (TEM). The incorporation of CNTs into a SiC matrix led to improved elastic modulus and fracture strength of the CNT/SiC nanofibers as compared to SiC alone. PMID- 27400779 TI - Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRbeta. AB - Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor beta (PDGFRbeta) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRbeta phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRbeta phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients. PMID- 27400778 TI - Clinical service use as people with Attention Deficit Hyperactivity Disorder transition into adolescence and adulthood: a prospective longitudinal study. AB - BACKGROUND: While Attention Deficit Hyperactivity Disorder (ADHD) often persists into adulthood, little is known about the needs and service use among adolescents and young adults with ADHD. The present study followed-up a cohort diagnosed with ADHD as children and assessed their: 1) needs, 2) correlates of contact with clinical services, and 3) experiences of transition from child to adult health services. METHODS: Ninety one young people aged 14-24 were recruited from the UK subset of the International Multi-Centre ADHD Genetics (IMAGE) Project. Affected young people and parents conducted face-to-face interviews and self-completion questionnaires including a modified version of the Client Services Receipt Inventory, The Barkley's ADHD rating scale, The Clinical Interview Schedule Revised, and the Zarit Burden Interview. Changes in key need characteristics (e.g. ADHD symptoms and impairments) over a 3-year period were examined using fixed effect models. Generalised Estimating Equations (GEE) were used to explore how key characteristics (such as ADHD symptoms) were associated with contact with clinical services across the three years. RESULTS: At baseline 62 % met diagnostic criteria for ADHD and presented with a range of ADHD related impairments, psychiatric comorbidities, and significant caregiver burden. While ADHD symptoms and related impairments lessened significantly over the three years, psychiatric comorbidities and caregiver burden remained stable. The strongest correlate of contact with clinical services was age (OR 0.65 95 % CI 0.49-0.84) with the odds of reported contact with clinical services decreasing by 35 % for each year increase in age at baseline and by 25 % for each year increase in age over time. Only 9 % of the sample had experienced a transfer to adult services, with the majority reporting unmet needs in healthcare transition. CONCLUSIONS: Despite continuing needs, few were in contact with adult health services or had received sufficient help with transition between child and adult health services. The main determinant of health service use for adolescents and young adults with ADHD is age - not needs. Service models should address the needs of ADHD individuals who are no longer children. PMID- 27400780 TI - How social representations of sexually transmitted infections influence experiences of genito-urinary symptoms and care-seeking in Britain: mixed methods study protocol. AB - BACKGROUND: Social understandings of sexually transmitted infections and associated symptoms and care-seeking behaviour continue to lag behind advancements in biomedical diagnostics and treatment, perpetuating the burden of disease. There is a lack of research linking perceptions, experiences and care seeking for sexual health issues, especially research conducted outside of medical settings. We aim to explore lay perceptions of STIs and how these influence experiences of genito-urinary symptoms and associated care-seeking behaviour, in women and men in Britain. METHODS AND DESIGN: This study adopts a participant-selection variant of the explanatory sequential mixed methods design to incorporate quantitative and qualitative strands. We use data from Britain's third National Survey of Sexual Attitudes and Lifestyles (n = 15,162) to analyse national patterns of symptom experience and care-seeking, and to identify a purposive qualitative sample. Semi-structured interviews (n = 27) following up with survey participants include a novel flash card activity providing qualitative data about infection perceptions, symptom experiences and decisions about healthcare. Quantitative and qualitative data are analysed separately using complex survey analyses and principles of Interpretative Phenomenological Analysis respectively. Data are then integrated in a subsequent phase of analysis using matrices to compare, contrast and identify silences from each method. DISCUSSION: This is an ongoing mixed methods study collecting, analysing and synthesising linked data from a national survey and follow-up semi-structured interviews. It adds explanatory potential to existing national survey data and is likely to inform future surveys about sexual health. Given the current uncertainty around service provision in Britain, this study provides timely data about symptom experiences and care-seeking behaviour which may inform future commissioning of sexual healthcare. PMID- 27400781 TI - Non-malaria fevers in a high malaria endemic area of Ghana. AB - BACKGROUND: The importance of fevers not due to malaria [non-malaria fevers, NMFs] in children in sub-Saharan Africa is increasingly being recognised. We have investigated the influence of exposure-related factors and placental malaria on the risk of non-malaria fevers among children in Kintampo, an area of Ghana with high malaria transmission. METHODS: Between 2008 and 2011, a cohort of 1855 newborns was enrolled and followed for at least 12 months. Episodes of illness were detected by passive case detection. The primary analysis covered the period from birth up to 12 months of age, with an exploratory analysis of a sub-group of children followed for up to 24 months. RESULTS: The incidence of all episodes of NMF in the first year of life (first and subsequent) was 1.60 per child-year (95 % CI 1.54, 1.66). The incidence of NMF was higher among infants with low birth weight [adjusted hazard ratio (aHR) 1.22 (95 % CI 1.04-1.42) p = 0.012], infants from households of poor socio-economic status [aHR 1.22 (95 % CI 1.02-1.46) p = 0.027] and infants living furthest from a health facility [aHR 1.20 (95 % CI 1.01 1.43) p = 0.037]. The incidence of all episodes of NMF was similar among infants born to mothers with or without placental malaria [aHR 0.97 (0.87, 1.08; p = 0.584)]. CONCLUSION: The incidence of NMF in infancy is high in the study area. The incidence of NMF is associated with low birth weight and poor socioeconomic status but not with placental malaria. PMID- 27400783 TI - Evaluation of two selection tests for recruitment into radiology specialty training. AB - BACKGROUND: This study evaluated whether two selection tests previously validated for primary care General Practice (GP) trainee selection could provide a valid shortlisting selection method for entry into specialty training for the secondary care specialty of radiology. METHODS: We conducted a retrospective analysis of data from radiology applicants who also applied to UK GP specialty training or Core Medical Training. The psychometric properties of the two selection tests, a clinical problem solving (CPS) test and situational judgement test (SJT), were analysed to evaluate their reliability. Predictive validity of the tests was analysed by comparing them with the current radiology selection assessments, and the licensure examination results taken after the first stage of training (Fellowship of the Royal College of Radiologists (FRCR) Part 1). RESULTS: The internal reliability of the two selection tests in the radiology applicant sample was good (alpha >= 0.80). The average correlation with radiology shortlisting selection scores was r = 0.26 for the CPS (with p < 0.05 in 5 of 11 shortlisting centres), r = 0.15 for the SJT (with p < 0.05 in 2 of 11 shortlisting centres) and r = 0.25 (with p < 0.05 in 5 of 11 shortlisting centres) for the two tests combined. The CPS test scores significantly correlated with performance in both components of the FRCR Part 1 examinations (r = 0.5 anatomy; r = 0.4 physics; p < 0.05 for both). The SJT did not correlate with either component of the examination. CONCLUSIONS: The current CPS test may be an appropriate selection method for shortlisting in radiology but would benefit from further refinement for use in radiology to ensure that the test specification is relevant. The evidence on whether the SJT may be appropriate for shortlisting in radiology is limited. However, these results may be expected to some extent since the SJT is designed to measure non-academic attributes. Further validation work (e.g. with non-academic outcome variables) is required to evaluate whether an SJT will add value in recruitment for radiology specialty training and will further inform construct validity of SJTs as a selection methodology. PMID- 27400782 TI - Does emergency department use and post-visit physician care cluster geographically and temporally for adolescents who self-harm? A population-based 9 year retrospective cohort study from Alberta, Canada. AB - BACKGROUND: Clustering of adolescent self-harming behaviours in the context of health care utilization has not been studied. We identified geographic areas with higher numbers of adolescents who (1) presented to an emergency department (ED) for self-harm, and (2) were without a physician follow-up visit for mental health within 14 days post-ED visit. METHODS: We extracted a population-based cohort of adolescents aged 15-17 years (n = 3,927) with ED visits during 2002-2011 in Alberta, Canada. We defined the case as an individual with one or more ED presentations for self-harm in the fiscal year of the analysis. Crude case rates were calculated and clusters were identified using a spatial scan. RESULTS: The rates decreased over time for ED visits for self-harm (differences: girls 199.6/100,000; p < 0.01; boys -58.8/100,000; p < 0.01), and for adolescents without a follow-up visit within 14 days following an ED visit for self-harm (differences: girls -108.3/100,000; p < 0.01; boys -61.9/100,000; p < 0.01). Two space-time clusters were identified: (1) a North zone cluster during 2002-2006 (p < 0.01) and (2) a South zone cluster during 2003-2007 (p < 0.01). These clusters had higher numbers of adolescents who presented to the ED for self-harm (relative risks [RRs]: 1.58 for cluster 1, 3.54 for cluster 2) and were without a 14-day physician follow-up (RRs: 1.78 for cluster 1, 4.17 for cluster 2). In 2010/2011, clusters in the North, Edmonton, and Central zones were identified for adolescents with and without a follow-up visit within 14 days following an ED visit for self-harm (p < 0.01). CONCLUSIONS: The rates for ED visits for adolescents who self-harm and rates of adolescents without a 14-day physician follow-up visit following emergency care for self-harm decreased during the study period. The space-time clusters identified the areas and years where visits to the ED by adolescents for self-harm were statistically higher than expected. These clusters can be used to identify locations where adolescents are potentially not receiving follow-up and the mental health support needed after emergency-based care. The 2010/2011 geographic cluster suggests that the northern part of the province still has elevated numbers of adolescents visiting the ED for self-harm. Prospective research is needed to determine outcomes associated with adolescents who receive physician follow-up following ED-based care for self harm compared to those who do not. PMID- 27400784 TI - Assessment of Different Intervention Models of Male Circumcision and Their Preliminary Effectiveness in Reducing HIV Incidence Among Drug Users in Western China. AB - World Health Organization (WHO) and Joint United Nations Program on AIDS (UNAIDS) recommend male circumcision (MC) as an additional HIV prevention measure. This study aimed to assess three models of promoting MC and their effects on preventing HIV infection among drug users in western China. We carried out a cohort study in three provinces of western China. HIV seronegative male drug users were recruited from methadone maintenance therapy clinics and cluster randomized into three intervention models. At baseline, 6, and 9 months of follow up, changes in MC knowledge, the acceptability of MC, MC surgery uptake, and the costs of model implementation were analyzed. Of 1,304 male drug users who were screened, 1,218 were enrolled in the study. The participants' knowledge about MC was significantly increased after interventions by all three models. The one stage model led to the highest increase in MC acceptability and the greatest increase in MC uptake. Multivariable Cox regression analysis showed that the one stage model was also the most effective method to promote MC uptake, compared with the two-stage model [rate ratio (RR) = 0.602; 95% confidence interval (CI), 0.420-0.862] and three-stage model (RR = 0.555; 95% CI, 0.382-0.807). The HIV incidence rate in the MC group was lower than that in the non-MC group (RR = 0.234; 95% CI, 0.056-0.974). Moreover, the one-stage model required the lowest cost per circumcision. The one-stage model is the most effective and the most cost-effective intervention to increase MC uptake among male drug users in western China and could decrease the HIV incidence rate, based on a short follow up investigation. PMID- 27400785 TI - YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/beta-catenin signaling pathway. AB - BACKGROUND: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored. METHODS: We evaluated YPEL3 expression in NPC cell lines and tissues using real time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/beta-catenin signaling pathway downstream genes using western blotting. RESULTS: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/beta-catenin signaling pathway downstream genes and the nuclear translocation of beta-catenin. CONCLUSIONS: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/beta-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment. PMID- 27400787 TI - A Shared-Electrode-Based Hybridized Electromagnetic-Triboelectric Nanogenerator. AB - Integration of electromagnetic generators (EMGs) and triboelectric nanogenerators (TENGs) can increase the total energy conversion efficiency from one mechanical motion by connecting the two devices in parallel after using power management circuits. A critical issue is how to realize the integration of the EMG and TENG in the same current circuits. Here, a hybridized nanogenerator, including an EMG and a TENG with the same set of electrodes, has been utilized to simultaneously scavenge mechanical energy. The hybridized nanogenerator can deliver a high output current of about 3.8 mA and a high output voltage of about 245 V when the switch in the device circuit was turned on and off, respectively. A acceleration sensor can be achieved by using the hybridized nanogenerator, where the detection sensitivities are about 143.2 V/(m/s(2)) for TENG and 291.7 MUA/(m/s(2)) for EMG. The fabricated hybridized nanogenerator may have practical use for scavenging mechanical energy and self-powered acceleration sensor systems. PMID- 27400786 TI - Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. AB - BACKGROUND: In the SOD1(G93A) mutant rat model of amyotrophic lateral sclerosis (ALS), neuronal death and rapid paralysis progression are associated with the emergence of activated aberrant glial cells that proliferate in the degenerating spinal cord. Whether pharmacological downregulation of such aberrant glial cells will decrease motor neuron death and prolong survival is unknown. We hypothesized that proliferation of aberrant glial cells is dependent on kinase receptor activation, and therefore, the tyrosine kinase inhibitor masitinib (AB1010) could potentially control neuroinflammation in the rat model of ALS. METHODS: The cellular effects of pharmacological inhibition of tyrosine kinases with masitinib were analyzed in cell cultures of microglia isolated from aged symptomatic SOD1(G93A) rats. To determine whether masitinib prevented the appearance of aberrant glial cells or modified post-paralysis survival, the drug was orally administered at 30 mg/kg/day starting after paralysis onset. RESULTS: We found that masitinib selectively inhibited the tyrosine kinase receptor colony stimulating factor 1R (CSF-1R) at nanomolar concentrations. In microglia cultures from symptomatic SOD1(G93A) spinal cords, masitinib prevented CSF-induced proliferation, cell migration, and the expression of inflammatory mediators. Oral administration of masitinib to SOD1(G93A) rats starting after paralysis onset decreased the number of aberrant glial cells, microgliosis, and motor neuron pathology in the degenerating spinal cord, relative to vehicle-treated rats. Masitinib treatment initiated 7 days after paralysis onset prolonged post paralysis survival by 40 %. CONCLUSIONS: These data show that masitinib is capable of controlling microgliosis and the emergence/expansion of aberrant glial cells, thus providing a strong biological rationale for its use to control neuroinflammation in ALS. Remarkably, masitinib significantly prolonged survival when delivered after paralysis onset, an unprecedented effect in preclinical models of ALS, and therefore appears well-suited for treating ALS. PMID- 27400788 TI - Consensus computational network analysis for identifying candidate outer membrane proteins from Borrelia spirochetes. AB - BACKGROUND: Similar to Gram-negative organisms, Borrelia spirochetes are dual membrane organisms with both an inner and outer membrane. Although the outer membrane contains integral membrane proteins, few of the borrelial outer membrane proteins (OMPs) have been identified and characterized to date. Therefore, we utilized a consensus computational network analysis to identify novel borrelial OMPs. RESULTS: Using a series of computer-based algorithms, we selected all protein-encoding sequences predicted to be OM-localized and/or to form beta barrels in the borrelial OM. Using this system, we identified 41 potential OMPs from B. burgdorferi and characterized three (BB0838, BB0405, and BB0406) to confirm that our computer-based methodology did, in fact, identify borrelial OMPs. Triton X-114 phase partitioning revealed that BB0838 is found in the detergent phase, which would be expected of a membrane protein. Proteolysis assays indicate that BB0838 is partially sensitive to both proteinase K and trypsin, further indicating that BB0838 is surface-exposed. Consistent with a prior study, we also confirmed that BB0405 is surface-exposed and associates with the borrelial OM. Furthermore, we have shown that BB0406, the product of a co transcribed downstream gene, also encodes a novel, previously uncharacterized borrelial OMP. Interestingly, while BB0406 has several physicochemical properties consistent with it being an OMP, it was found to be resistant to surface proteolysis. Consistent with BB0405 and BB0406 being OMPs, both were found to be capable of incorporating into liposomes and exhibit pore-forming activity, suggesting that both proteins are porins. Lastly, we expanded our computational analysis to identify OMPs from other borrelial organisms, including both Lyme disease and relapsing fever spirochetes. CONCLUSIONS: Using a consensus computer algorithm, we generated a list of candidate OMPs for both Lyme disease and relapsing fever spirochetes and determined that three of the predicted B. burgdorferi proteins identified were indeed novel borrelial OMPs. The combined studies have identified putative spirochetal OMPs that can now be examined for their roles in virulence, physiology, and disease pathogenesis. Importantly, the studies described in this report provide a framework by which OMPs from any human pathogen with a diderm ultrastructure could be cataloged to identify novel virulence factors and vaccine candidates. PMID- 27400789 TI - Human Induced Pluripotent Stem Cells Differentiate Into Functional Mesenchymal Stem Cells and Repair Bone Defects. AB - : : Mesenchymal stem cells (MSCs) are currently the most established cells for skeletal tissue engineering and regeneration; however, their availability and capability of self-renewal are limited. Recent discoveries of somatic cell reprogramming may be used to overcome these challenges. We hypothesized that induced pluripotent stem cells (iPSCs) that were differentiated into MSCs could be used for bone regeneration. Short-term exposure of embryoid bodies to transforming growth factor-beta was used to direct iPSCs toward MSC differentiation. During this process, two types of iPSC-derived MSCs (iMSCs) were identified: early (aiMSCs) and late (tiMSCs) outgrowing cells. The transition of iPSCs toward MSCs was documented using MSC marker flow cytometry. Both types of iMSCs differentiated in vitro in response to osteogenic or adipogenic supplements. The results of quantitative assays showed that both cell types retained their multidifferentiation potential, although aiMSCs demonstrated higher osteogenic potential than tiMSCs and bone marrow-derived MSCs (BM-MSCs). Ectopic injections of BMP6-overexpressing tiMSCs produced no or limited bone formation, whereas similar injections of BMP6-overexpressing aiMSCs resulted in substantial bone formation. Upon orthotopic injection into radial defects, all three cell types regenerated bone and contributed to defect repair. In conclusion, MSCs can be derived from iPSCs and exhibit self-renewal without tumorigenic ability. Compared with BM-MSCs, aiMSCs acquire more of a stem cell phenotype, whereas tiMSCs acquire more of a differentiated osteoblast phenotype, which aids bone regeneration but does not allow the cells to induce ectopic bone formation (even when triggered by bone morphogenetic proteins), unless in an orthotopic site of bone fracture. SIGNIFICANCE: Mesenchymal stem cells (MSCs) are currently the most established cells for skeletal tissue engineering and regeneration of various skeletal conditions; however, availability of autologous MSCs is very limited. This study demonstrates a new method to differentiate human fibroblast-derived induced pluripotent stem cells (iPSCs) to cells with MSC properties, which we comprehensively characterized including differentiation potential and transcriptomic analysis. We showed that these iPS-derived MSCs are able to regenerate nonunion bone defects in mice more efficiently than bone marrow-derived human MSCs when overexpressing BMP6 using a nonviral transfection method. PMID- 27400790 TI - Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis. AB - : : Fast remyelination by endogenous oligodendrocyte precursor cells (OPCs) is essential to prevent axonal and subsequent retrograde neuronal degeneration in demyelinating lesions in multiple sclerosis (MS). In chronic lesions, however, the remyelination capacity of OPCs becomes insufficient. Cell therapy with exogenous remyelinating cells may be a strategy to replace the failing endogenous OPCs. Here, we differentiated human induced pluripotent stem cells (hiPSCs) into OPCs and validated their proper functionality in vitro as well as in vivo in mouse models for MS. Next, we intracerebrally injected hiPSC-derived OPCs in a nonhuman primate (marmoset) model for progressive MS; the grafted OPCs specifically migrated toward the MS-like lesions in the corpus callosum where they myelinated denuded axons. hiPSC-derived OPCs may become the first therapeutic tool to address demyelination and neurodegeneration in the progressive forms of MS. SIGNIFICANCE: This study demonstrates for the first time that human induced pluripotent stem cell (iPSC)-derived oligodendrocyte precursor cells (OPCs), after intracortical implantation in a nonhuman primate model for progressive multiple sclerosis (MS), migrate to the lesions and remyelinate denuded axons. These findings imply that human iPSC-OPCs can be a therapeutic tool for MS. The results of this feasibility study on the potential use of hiPSC derived OPCs are of great importance for all MS researchers focusing on the stimulation of remyelination in MS patients. Further optimization and research on practical issues related to the safe production and administration of iPSC derived cell grafts will likely lead to a first clinical trial in a small group of secondary progressive MS patients. This would be the first specific therapeutic approach aimed at restoring myelination and rescuing axons in MS patients, since there is no treatment available for this most debilitating aspect of MS. PMID- 27400791 TI - In Pursuit of Authenticity: Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Clinical Applications. AB - : : Induced pluripotent stem cells (iPSCs) can be efficiently differentiated into retinal pigment epithelium (RPE), offering the possibility of autologous cell replacement therapy for retinal degeneration stemming from RPE loss. The generation and maintenance of epithelial apical-basolateral polarity is fundamental for iPSC-derived RPE (iPSC-RPE) to recapitulate native RPE structure and function. Presently, no criteria have been established to determine clonal or donor based heterogeneity in the polarization and maturation state of iPSC-RPE. We provide an unbiased structural, molecular, and physiological evaluation of 15 iPSC-RPE that have been derived from distinct tissues from several different donors. We assessed the intact RPE monolayer in terms of an ATP-dependent signaling pathway that drives critical aspects of RPE function, including calcium and electrophysiological responses, as well as steady-state fluid transport. These responses have key in vivo counterparts that together help determine the homeostasis of the distal retina. We characterized the donor and clonal variation and found that iPSC-RPE function was more significantly affected by the genetic differences between different donors than the epigenetic differences associated with different starting tissues. This study provides a reference dataset to authenticate genetically diverse iPSC-RPE derived for clinical applications. SIGNIFICANCE: The retinal pigment epithelium (RPE) is essential for maintaining visual function. RPE derived from human induced pluripotent stem cells (iPSC-RPE) offer a promising cell-based transplantation therapy for slowing or rescuing RPE induced visual function loss. For effective treatment, iPSC-RPE must recapitulate the physiology of native human RPE. A set of physiologically relevant functional assays are provided that assess the polarized functional activity and maturation state of the intact RPE monolayer. The present data show that donor-to-donor variability exceeds the tissue-to-tissue variability for a given donor and provides, for the first time, criteria necessary to identify iPSC-RPE most suitable for clinical application. PMID- 27400792 TI - Human Mesenchymal Stem Cells Impact Th17 and Th1 Responses Through a Prostaglandin E2 and Myeloid-Dependent Mechanism. AB - : : Human mesenchymal stem cells (hMSCs) are being increasingly pursued as potential therapies for immune-mediated conditions, including multiple sclerosis. Although they can suppress human Th1 responses, they reportedly can reciprocally enhance human Th17 responses. Here, we investigated the mechanisms underlying the capacity of hMSCs to modulate human Th1 and Th17 responses. Human adult bone marrow-derived MSCs were isolated, and their purity and differentiation capacity were confirmed. Human venous peripheral blood mononuclear cells (PBMC) were activated, alone, together with hMSC, or in the presence of hMSC-derived supernatants (sups). Cytokine expression by CD4+ T-cell subsets (intracellular staining by fluorescence-activated cell sorting) and secreted cytokines (enzyme linked immunosorbent assay) were then quantified. The contribution of prostaglandin E2 (PGE2) as well as of myeloid cells to the hMSC-mediated regulation of T-cell responses was investigated by selective depletion of PGE2 from the hMSC sups (anti-PGE2 beads) and by the selective removal of CD14+ cells from the PBMC (magnetic-activated cell sorting separation). Human MSC-secreted products could reciprocally induce interleukin-17 expression while decreasing interferon-gamma expression by human CD4+ T cells, both in coculture and through soluble products. Pre-exposure of hMSCs to IL-1beta accentuated their capacity to reciprocally regulate Th1 and Th17 responses. Human MSCs secreted high levels of PGE2, which correlated with their capacity to regulate the T-cell responses. Selective removal of PGE2 from the hMSC supernatants abrogated the impact of hMSC on the T cells. Selective removal of CD14+ cells from the PBMCs also limited the capacity of hMSC-secreted PGE2 to affect T-cell responses. Our discovery of a novel PGE2-dependent and myeloid cell-mediated mechanism by which human MSCs can reciprocally induce human Th17 while suppressing Th1 responses has implications for the use of, as well as monitoring of, MSCs as a potential therapeutic for patients with multiple sclerosis and other immune-mediated diseases. SIGNIFICANCE: Although animal studies have generated a growing interest in the anti-inflammatory potential of mesenchymal stem cells (MSCs) for the treatment of autoimmune diseases, MSCs possess the capacity to both limit and promote immune responses. Yet relatively little is known about human-MSC modulation of human disease-implicated T-cell responses, or the mechanisms underlying such modulation. The current study reveals a novel prostaglandin E2-dependent and myeloid cell-mediated mechanism by which human MSCs can reciprocally regulate human Th17 and Th1 responses, with implications for the use of MSCs as a potential therapeutic for patients with multiple sclerosis and other immune mediated diseases. PMID- 27400793 TI - Autophagy Improves the Immunosuppression of CD4+ T Cells by Mesenchymal Stem Cells Through Transforming Growth Factor-beta1. AB - : : Mesenchymal stem cells (MSCs) have been extensively investigated as a promising approach to treat many autoimmune and inflammatory diseases. The stress condition would affect the therapeutic efficacy and induce autophagy of MSCs. However, whether autophagy would affect the immunosuppressive capacity of MSCs is largely unknown. The present study aimed to assess whether autophagy plays an important role in regulating the immunomodulation of MSCs and the undermechanisms. We successfully inhibited and induced autophagy of MSCs using 3 methyladenine (3-MA) and rapamycin, respectively. Our results demonstrated that rapamycin strengthened the capacity of MSCs to inhibit CD4+ T-cell proliferation, whereas 3-MA weakened the inhibitory ability of MSCs. Mechanistically, 3-MA pretreated MSCs secreted less, whereas rapamycin-pretreated MSCs secreted more transforming growth factor-beta1 (TGF-beta1) compared with the control cells. Furthermore, exogenous TGF-beta1 addition recovered the immunosuppressive capacity of 3-MA-pretreated MSCs, whereas exogenous anti-TGF-beta1 antibody addition reduced the immunosuppressive capacity of rapamycin-pretreated MSCs. These results indicated that the autophagy level regulates the immunosuppression of CD4+ T cells by MSCs through affecting TGF-beta1 secretion and provides a novel method for improving the therapeutic efficacy of MSCs by activating autophagy. SIGNIFICANCE: Mesenchymal stem cell (MSC)-based therapy is a promising tool to treat many diseases. Autophagy occurred in MSCs during their application, especially in those exposed to stress conditions. However, whether autophagy will affect the therapeutic efficacy of MSCs is largely unknown. This study makes a significant contribution to demonstrate that autophagy could improve the immunosuppression of CD4+ T cells by mesenchymal stem cells through transforming growth factor-beta1. Therefore, regulation of autophagy in MSCs would provide a promising strategy to improve the therapeutic efficacy of these cells. PMID- 27400794 TI - A Simple Method to Determine the Purity of Adipose-Derived Stem Cell-Based Cell Therapies. AB - : : It is important to standardize methods to quantify the purity of adipose tissue-derived cells for regenerative medicine. We developed a simple and robust tool to discriminate fibroblasts and adipose stem cells (ASCs) by testing release of specific growth factors. ASCs and dermal fibroblasts (DFs) were isolated from human donors (n = 8). At passage 4, cultures were prepared with progressive ASC/DF ratios of 100%/0%, 75%/25%, 50%/50%, 25%/75%, and 0%/100% for each donor and incubated in hypoxic chambers at 0.1% and 5% O2 and hyperglycemia at 1.0 and 4.5 g/l. After incubation for 24 hours, cell survival, proliferation, and growth factor release (vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], insulin-like growth factor 1 [IGF-1], stromal cell-derived factor 1alpha [SDF-1alpha], and basic fibroblast growth factor [bFGF]) were assessed for each condition. The proliferation and viability of ASCs and DFs were not impacted by the oxygen tension conditions. No significant difference in HGF, IGF-1, bFGF, and keratinocyte growth factor secretome was found across the various ASC/DF ratios. Interestingly, a negative relation for VEGF secretion was found when ASCs were contaminated by fibroblasts, especially when cells were exposed to 4.5 g/l glucose and 0.1% O2 (R = -0.521; p < .001). In contrast, secretion of SDF-1alpha was positively correlated with the fibroblast ratio, more prominently in low glucose and low oxygen tension (r = .657; p < .001). Above and beyond these previously unreported metabolic features, these results (a) allow us to discriminate fibroblasts and ASCs specifically and (b) allow new tools be developed for the rapid testing (a response within 24 hours) for the release of ASC-based therapies. SIGNIFICANCE: In order to provide direction to academia, industry, and regulatory authorities regarding purity assessment for adipose tissue-derived cells, this report describes a simple tool to facilitate development of international standards based on reproducible parameters and endpoints that may systematize cellular products across boundaries and accelerate the delivery of safe and effective adipose stem cell (ASC)-based tools to the medical community and the patients it serves. This tool (a) can discriminate specifically fibroblasts and ASCs and (b) can be rapidly implemented and performed before the release of the ASC-based therapy (a response within 24 hours). PMID- 27400795 TI - Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF beta Secretion. AB - : : The regulation of microglial cell phenotype is a potential therapeutic intervention in neurodegenerative disease. Previously, we reported that transforming growth factor-beta (TGF-beta) levels in mesenchymal stromal cells (MSCs) could be used as potential biological markers to predict the effectiveness of autologous MSC therapy in patients with amyotrophic lateral sclerosis. However, the underlying mechanism of TGF-beta in MSCs was not fully elucidated in determining the functional properties of microglia. In this study, we aimed to clarify the role of TGF-beta that is involved in MSC effectiveness, especially focusing on microglia functional properties that play a pivotal role in neuroinflammation. We found that MSC-conditioned media (MSC-CM) inhibited proinflammatory cytokine expression, restored alternative activated microglia phenotype markers (fractalkine receptor, mannose receptor, CD200 receptor), and enhanced phagocytosis in lipopolysaccharide (LPS)-stimulated microglia. In addition, TGF-beta in MSC-CM played a major role in these effects by inhibiting the nuclear factor-kappaB pathway and restoring the TGF-beta pathway in LPS stimulated microglia. Recombinant TGF-beta also induced similar effects to MSC-CM in LPS-stimulated microglia. Therefore, we propose that MSCs can modulate the functional properties of microglia via TGF-beta secretion, switching them from a classically activated phenotype to an inflammation-resolving phenotype. The latter role may be associated with the inhibition of neuroinflammatory processes in neurodegenerative disorders. SIGNIFICANCE: The results of this study showed that microglia functional properties may be modulated depending on the composition and quantity of mesenchymal stromal cell (MSC)-secreting factors. Transforming growth factor (TGF)-beta is proposed as a modulator of microglia functional properties among MSC-secreting factors, and this study aligns with a previous clinical study by these same authors. TGF-beta releasing capacity could be an important factor enhancing the therapeutic efficacy of MSCs in clinical trials. PMID- 27400796 TI - High-Efficiency Serum-Free Feeder-Free Erythroid Differentiation of Human Pluripotent Stem Cells Using Small Molecules. AB - : : This article describes a good manufacturing practice (GMP)-compatible, feeder free and serum-free method to produce large numbers of erythroid cells from human pluripotent stem cells (hPSCs), either embryonic or induced. This multistep protocol combines cytokines and small molecules to mimic and surpass the early stages of development. It produces, without any selection or sorting step, a population of cells in which 91.8% +/- 5.4% express CD34 at day 7, 98.6% +/- 1.3% express CD43 at day 10, and 99.1% +/- 0.95% of cells are CD235a positive by day 31 of the differentiation process. Moreover, this differentiation protocol supports extensive expansion, with a single hPSC producing up to 150 hematopoietic progenitor cells by day 10 and 50,000-200,000 erythroid cells by day 31. The erythroid cells produced exhibit a definitive fetal hematopoietic type, with 90%-95% fetal globin and variable proportion of embryonic and adult globin at the protein level. The presence of small molecules during the differentiation protocol has quantitative and qualitative effects; it increases the proportion of adult globin and decreases the proportion of embryonic globin. Given its level of definition, this system provides a powerful tool for investigation of the mechanisms governing early hematopoiesis and erythropoiesis, including globin switching and enucleation. The early stages of the differentiation protocol could also serve as a starting point for the production of endothelial cells and other hematopoietic cells, or to investigate the production of long-term reconstituting hematopoietic stem cells from hPSCs. SIGNIFICANCE: This differentiation protocol allows the production of a large amount of erythroid cells from pluripotent stem cells. Its efficiency is compatible with that of in vitro red blood cell production, and it can be a considerable asset for studying developmental erythropoiesis and red blood cell enucleation, thereby aiding both basic and translational research. In addition to red cells, the early stages of the protocol could also be used as a starting point for the large-scale production of other hematopoietic cell types, including the ultimate goal of generating long-term reconstituting hematopoietic stem cells. PMID- 27400797 TI - Externally Applied Static Magnetic Field Enhances Cardiac Retention and Functional Benefit of Magnetically Iron-Labeled Adipose-Derived Stem Cells in Infarcted Hearts. AB - : : Although adipose-derived stem cells (ASCs) hold the promise of effective therapy for myocardial infarction, low cardiac retention of implanted ASCs has hindered their therapeutic efficiency. We investigated whether an externally applied static magnetic field (SMF) enhances cardiac localization of "magnetic" cells and promotes heart function recovery when ASCs are preloaded with superparamagnetic iron oxide (SPIO) nanoparticles. The influence of SMF (0.1 Tesla) on the biological activities of SPIO-labeled ASCs (SPIOASCs) was investigated first. Fifty-six female rats with myocardial infarction underwent intramyocardial injection of cell culture medium (CCM) or male SPIOASCs with or without the subcutaneous implantable magnet (CCM-magnet or SPIOASC-magnet). Four weeks later, endothelial differentiation, angiogenic cytokine secretion, angiogenesis, cardiomyocyte apoptosis, cell retention, and cardiac performance were examined. The 0.1-Tsela SMF did not adversely affect the viability, proliferation, angiogenic cytokine secretion, and DNA integrity of SPIOASCs. The implanted SPIOASCs could differentiate into endothelial cell, incorporate into newly formed vessels, and secrete multiple angiogenic cytokines. Four weeks after cell transplantation, the number of cardiac SPIOASCs was significantly increased, vascular density was markedly enlarged, fewer apoptotic cardiomyocytes were present, and heart contractile function was substantially improved in the SPIOASC magnet treated rats in comparison with the SPIOASC-treated rats. The SPIOASCs could differentiate into endothelial cells, incorporate into vessels, promote angiogenesis, and inhibit ischemic cardiomyocyte apoptosis. An externally applied SMF offered a secure environment for biological properties of SPIOASCs, increased the cardiac retention of implanted magnetic SPIOASCs, and further enhanced heart function recovery after myocardial infarction. SIGNIFICANCE: This pilot proof-of concept study suggests that a 0.1-Tesla static magnetic field does not adversely affect the viability, proliferation, angiogenic cytokine secretion, or DNA integrity of the superparamagnetic iron oxide-labeled adipose-derived stem cells (SPIOASCs). Implantation of adipose-derived stem cells promotes myocardial neovascularization and inhibits ischemic cardiomyocyte apoptosis through endothelial differentiation, incorporation into vessels, and paracrine factor secretion. An externally applied static magnetic field enhanced myocardial retention of intramyocardially injected "magnetic" SPIOASCs and promoted cardiac function recovery after myocardial infarction. With further preclinical optimization, this approach may improve the outcome of current stem cell therapy for ischemic myocardial infarction. PMID- 27400798 TI - Epidermal Growth Factor Tethered to beta-Tricalcium Phosphate Bone Scaffolds via a High-Affinity Binding Peptide Enhances Survival of Human Mesenchymal Stem Cells/Multipotent Stromal Cells in an Immune-Competent Parafascial Implantation Assay in Mice. AB - : : Mesenchymal stem cells/multipotent stromal cells (MSCs) are attractive candidates for cell therapies owing to their ability to differentiate into many lineages. However, these cells often fail to survive when implanted into a harsh wound environment, limiting efficacy in vivo. To improve MSC survival, we previously found that tethered epidermal growth factor (tEGF) molecules that restrict epidermal growth factor receptor (EGFR) signaling to the cell surface provide resistance to death signals. To adapt this system to wound healing, we tethered epidermal growth factor (EGF) to tricalcium phosphate (TCP) particle scaffolds, clinically used in bone healing. Human primary MSCs seeded on TCP and mixed into a collagen-based gel were injected in the perifascial space of immunocompetent mice with or without tEGF attached to the surface. We found that tethering EGF to the TCP scaffolds yielded approximately a fourfold increase in MSC survival compared with non-EGF scaffolds at 21 days, as well as significant improvements in survival in the short term at 2 and 7 days after implantation. Overall, our approach to sustaining EGFR signaling reduced MSC death in vivo and may be useful for future cell therapies where MSCs typically die on implantation. SIGNIFICANCE: Stem cells are limited as tissue replacements owing to rapid death induced in the hostile wound environment. It has been found that restricting epidermal growth factor (EGF) receptor signaling to the membrane provides a survival advantage. This report elucidates a method to tether EGF to bone induction material to improve the survival of mesenchymal stem cells/multipotent stromal cells in vivo. PMID- 27400800 TI - Mechano-switchable, luminescent gels derived from salts of a long-chained, fatty acid gelator. AB - Stimulus-responsive molecular gel systems, based on metal salts of a luminescent gelator, 9,10-dioxooctadecanoic acid (DODA), are reported. These salts are structurally the simplest metallo-gelators of which we are aware that exhibit controllable mechano-responsive and luminescent properties. Aggregation is more favored by the metal salts than for DODA itself. However, gelation ability differs dramatically depending on the metal ion: whereas the salts with zinc(ii) and calcium(ii) are inefficient gelators, those with nickel(ii) and copper(ii) can gelate various aromatic liquids, alkanes, and long-chained alcohols. Unlike the DODA gels, no aggregation-induced shift in the positions of the emission spectra of the metal salts could be observed as the sols were transformed to their gel phases. Gels of both nickel(ii) and copper(ii) salts in benzonitrile are among the few known examples with crystalline networks and exhibiting thixotropic behavior. However, there are significant differences in their abilities to recover the initial viscoelastic properties. Structural data for the solid and gel states lead us to conclude that differences among the gelating abilities can be attributed principally to the specific nature of interactions of the salts at their head groups. They appear to control the mechanical and emissive properties of the gels as well as whether the initial aggregation of the salts in the sol phases will support the growth of 1D objects that are capable of maintaining strong contacts, leading to 3D networks and gel formation. Overall, the results provide a facile strategy for the design of luminescent materials with controllable mechano-responsiveness by modifying the metal ions within fibrillar assemblies. PMID- 27400799 TI - MicroRNA-146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury. AB - : : The role of mesenchymal stem cells (MSCs) in kidney injury repair has been studied widely. However, the underlying molecular mechanism remains unclear. We profiled the altered microRNAs in renal tissues from cisplatin-induced acute kidney injury (AKI) rats treated with or without rat bone marrow MSCs (rMSCs). We observed that microRNA-146b (miR-146b) expression was considerably upregulated in renal tissues from AKI rats compared with that in healthy rats, and the expression decreased following MSC treatment after cisplatin administration. At the early stage of AKI, serum miR-146b levels exhibited a rapid increase that was even faster than that of two conventional renal function indexes: serum creatinine and blood urea nitrogen levels. Furthermore, the serum miR-146b levels in AKI patients were higher than those in healthy people. In vitro exposure to cisplatin also increased miR-146b expression in renal tubular epithelial cells (TECs). miR-146b knockdown protected renal TECs from cisplatin-induced apoptosis and promoted their proliferation. Moreover, ErbB4 was identified as a direct target of miR-146b, and miR-146b inhibition induced ErbB4 expression, resulting in enhanced proliferation of injured renal TECs. In addition, restoration by rMSCs could be controlled through ErbB4 downregulation. In conclusion, elevated miR-146b expression contributes to cisplatin-induced AKI, partly through ErbB4 downregulation. miR-146b might be an early biomarker for AKI, and miR-146b inhibition could be a novel strategy for AKI treatment. SIGNIFICANCE: The present study found that microRNA-146b (miR-146b) might be a novel biomarker for acute kidney injury and an indicator for its recovery after treatment with mesenchymal stem cells (MSCs). The results showed that in acute kidney injury induced by cisplatin, miR-146b in serum increased more quickly than did the usual indexes of kidney injury and decreased with restoration of MSCs. In addition, inhibition of miR-146b could ameliorate the apoptosis induced by cisplatin and potentially improve the proliferation by freeing ErbB4 and its downstream proteins. PMID- 27400801 TI - Scaling theory of [Formula: see text] topological invariants. AB - For inversion-symmetric topological insulators and superconductors characterized by [Formula: see text] topological invariants, two scaling schemes are proposed to judge topological phase transitions driven by an energy parameter. The scaling schemes renormalize either the phase gradient or the second derivative of the Pfaffian of the time-reversal operator, through which the renormalization group flow of the driving energy parameter can be obtained. The Pfaffian near the time reversal invariant momentum is revealed to display a universal critical behavior for a great variety of models examined. PMID- 27400802 TI - The ethics of ambulance ramping. AB - Ramping is the practice of requiring paramedics to continue to care for patients rather than hand over clinical responsibility to the ED. It arose as an alternative to admitting patients to EDs that are deemed to be already operating at or beyond capacity. This paper analyses the ethics of ramping. Ramping has been embraced by some ED practitioners and policymakers as a solution to the problem of ED patients suffering increased risks of harm as a result of waiting times within ED. However, this perspective fails to adequately consider the implications, especially the opportunity cost of requiring paramedics to remain at the hospital rather than make themselves available for other patients. From this perspective, ramping negatively impacts the wider provision of emergency medical services, with potentially serious consequences for people's health. Advocates of ramping must consider people in the community who require a medical emergency response. PMID- 27400803 TI - Total antioxidant intake and prostate cancer in the Cancer of the Prostate in Sweden (CAPS) study. A case control study. AB - BACKGROUND: The total intake of dietary antioxidants may reduce prostate cancer risk but available data are sparse and the possible role of supplements unclear. We investigated the potential association between total and dietary antioxidant intake and prostate cancer in a Swedish population. METHODS: We used FFQ data from 1499 cases and 1112 controls in the population based case-control study Cancer of the Prostate in Sweden (CAPS). The ferric reducing antioxidant potential (FRAP) assay was used to assess the total antioxidant capacity (TAC) of diet and supplements. We calculated odds ratios (ORs) for the risk of prostate cancer across quintiles of antioxidant intake from all foods, from fruit and vegetables only, and from dietary supplements using unconditional logistic regression. RESULTS: Coffee comprised 62 % of the dietary antioxidant intake, tea 4 %, berries 4 %, chocolate 2 %, and boiled potatoes 2 %. In total 19 % and 13 % of the population took multivitamins and supplemental Vitamin C respectively, on a regular basis. Antioxidant intake from all foods and from fruits and vegetables separately measured by the FRAP assay was not associated with prostate cancer risk. For antioxidant intake from supplements we found a positive association with total, advanced, localized, high grade and low grade prostate cancer in those above median supplemental TAC intake of users compared to non-users (Adjusted ORs for total prostate cancer: 1.37, 95 % CI 1.08-1.73, advanced: 1.51, 95 % CI 1.11-2.06, localized: 1.36. 95 % CI 1.06-1.76, high grade 1.60, 95 % CI 1.06-2.40, low grade 1.36, 95 % CI 1.03-1.81). A high intake of coffee (>=6 cups/day) was associated with a possible risk reduction of fatal and significantly with reduced risk for high grade prostate cancer, adjusted OR: 0.45 (95 % CI: 0.22-0.90), whereas a high intake of chocolate was positively associated with risk of total, advanced, localized and low grade disease (adjusted OR for total: 1.43, 95 % CI 1.12-1.82, advanced: 1.40, 95 % CI 1.01 1.96, localized: 1.43, 95 % CI 1.08-1.88, low-grade: 1.41, 95 % CI 1.03-1.93). CONCLUSIONS: Total antioxidant intake from diet was not associated with prostate cancer risk. Supplement use may be associated with greater risk of disease. PMID- 27400804 TI - A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene. AB - BACKGROUND: Recessive mutations in the 3-hydroxyisobutyryl-CoA hydrolase gene (HIBCH) are associated with a rare neurodegenerative disease that affects the basal ganglia. Most patients die during infancy or early childhood. Here we describe 5 adolescent and adult patients from 2 unrelated families, who presented with a movement disorder and MRI features suggestive of Leigh syndrome. METHODS: Clinical and metabolic assessment was followed by autozygosity mapping and whole exome and Sanger sequencing. HIBCH enzyme activity and the bioenergetic profile were determined in patient fibroblasts. RESULTS: The movement disorder was dominated by ataxia in one family and by dystonia in the other. All affected family members carried the identical homozygous c.913A>G (p.T305A) HIBCH mutation. Enzyme activity was reduced, and a valine challenge reduced the oxygen consumption rate. CONCLUSIONS: We report the first adult patients with HIBCH deficiency and a disease course much milder than previously reported, thereby expanding the HIBCH-associated phenotypic spectrum. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27400805 TI - Got Rice? An Unusual Case of Iodine-Deficiency Hypothyroidism. PMID- 27400806 TI - Popular Mobile Phone Apps for Diet and Weight Loss: A Content Analysis. AB - BACKGROUND: A review of the literature has revealed that the rates of overweight and obesity have been increasing in Australia over the last two decades and that wellness mobile phone apps play a significant role in monitoring and managing individuals' weight. Although mobile phone app markets (iTunes and Google Play) list thousands of mobile phone health apps, it is not always clear whether those apps are supported by credible sources. Likewise, despite the prevailing use of mobile phone apps to aid with weight management, the usability features of these apps are not well characterized. OBJECTIVE: The research explored how usability taxonomy could inform the popularity of downloaded, socially focused wellness mobile phone apps, in particular weight loss and diet apps. The aim of the study was to investigate the Australian mobile phone app stores (iTunes and Google Play) in order to examine the usability features of the most popular (ie, most downloaded) wellness apps. METHODS: The design of this study comprises 3 main stages: stage 1, identifying apps; stage 2, development of weight loss and diet evaluation framework; and stage 3, application of the evaluation framework. Each stage includes specific data collection, analysis tools, and techniques. RESULTS: The study has resulted in the development of a justified evaluation framework for weight loss and diet mobile phone apps. Applying the evaluation framework to the identified apps has shown that the most downloaded iTunes and Google Play apps are not necessarily the most usable or effective. In addition, the research found that search algorithms for iTunes and Google Play are biased toward apps' titles and keywords that do not accurately define the real functionality of the app. Moreover, the study has also analyzed the apps' user reviews, which served as justification for the developed evaluation framework. CONCLUSIONS: The analysis has shown that ease of use, reminder, bar code scanning, motivation, usable for all, and synchronization are significant attributes that should be included in weight loss and diet mobile phone apps and ultimately in potential weight loss and diet evaluation frameworks. PMID- 27400807 TI - Can Breast Cancer Biopsy Influence Sentinel Lymph Node Status? AB - INTRODUCTION: We evaluated whether the needle size could influence metastasis occurrence in the axillary sentinel lymph node (SLN) in ultrasound-guided core needle biopsy (US-CNB) of breast cancer (BC). MATERIALS AND METHODS: The data from all patients with breast lesions who had undergone US-CNB at our institution from January 2011 to January 2015 were retrospectively reviewed. A total of 377 BC cases were included using the following criteria: (1) percutaneous biopsy proven invasive BC; and (2) SLN dissection with histopathologic examination. The patients were divided into 2 groups according to the needle size used: 14 gauge versus 16 or 18 gauge. SLN metastasis classification followed the 7th American Joint Committee on Cancer (2010) TNM pathologic staging factors: macrometastases, micrometastases, isolated tumor cells, or negative. Only macrometastases and micrometastases were considered positive, and the positive and negative rates were calculated for the overall population and for both needle size groups. RESULTS: Of the 377 BC cases, 268 US-CNB procedures were performed using a 14 gauge needle and 109 with a 16- or 18-gauge needle, respectively. The negative rate was significantly related statistically with the needle size, with a greater prevalence in the 14-gauge group on both extemporaneous analysis (P = .019) and definitive analysis (P = .002). The macrometastasis rate was 17% (63 of 377) for the 14-gauge and 3% (12 of 377) for the 16- and 18-gauge needles, respectively. CONCLUSION: Our preliminary results have suggested that use of a large needle size in CNB does not influence SLN status; thus, preoperative breast biopsy can be considered a safe procedure in the diagnosis of malignant breast lesions. PMID- 27400808 TI - Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of beta-Thujaplicin Derivatives. AB - Natural beta-thujaplicin displays a remarkable array of biological activities for the prevention or treatment of various disorders while its tropolone scaffold inspired the synthesis of new analogs. The main goal of the current study was to evaluate the influence of 4-substituted piperazine moieties at position 7 of the beta-thujaplicin scaffold, on the antimicrobial activity. In order to determine the biological activity of the beta-thujaplicin derivatives, a microdilution method was used against a wide variety of bacteria and fungi. Pseudomonas aeruginosa PAO 1 was used for testing antiquorum and antibiofilm effects. Four human tumor cell lines (MCF-7, NCI-H460, HeLa, and HepG2) and a porcine liver derived cell line (PLP2) were used for testing antitumor and cytotoxic activity. The compounds present better antibacterial and antifungal activity in comparison with approved antimicrobials used as control agents. beta-Thujaplicin showed strong antibacterial and antifungal activities against all tested species. Further studies of their antibacterial activity revealed that all compounds presented good antibiofilm and antiquorum effects. Fungi were more susceptible than bacteria to the tested compounds, with the exception of MK150, which possessed the best antibacterial effect. None of the tested compounds, at the GI50 values obtained for the tumor cell lines, have shown toxicity for non-tumor liver cells (PLP2). The prediction of physicochemical properties of the compounds was performed to further explain the structure-activity relationship. Finally, in order to explore a possible mechanism of action of the synthesized compounds, molecular docking studies were performed on CYP51 (14-a lanosterol demethylase), an important component of the fungal cell membrane. PMID- 27400809 TI - Epidemiology of post-adolescence acne and adolescence acne in Singapore: a 10 year retrospective and comparative study. AB - INTRODUCTION: Acne vulgaris commonly affects adolescents. But recent reports suggest a rising prevalence of post-adolescence acne. While there are few reports on post-adolescence acne, there are even fewer reports comparing adolescence acne and post-adolescence. METHODS: Epidemiological data of adolescence (<25 years) and post-adolescence (>=25 years) acne patients diagnosed between 2004 and 2013 in a tertiary dermatology referral centre was analysed. From the pool of patients seen in 2010, 80 adolescence and 84 post-adolescence acne patients' epidemiological characteristics and treatment responses were analysed. RESULTS: During the 10-year study period, there was an increase in the number and proportion of acne cases. In 2004, 4447 (5.77%) of all new diagnoses made were of acne vulgaris. The proportion rose to 5723 (8.13%) in 2013. There were consistently more female than male acne patients. The proportion of post adolescent cases remained constant at about 30% of all acne patients seen. Mean age of acne vulgaris patients decreased from 23.1 years in 2004 to 22.6 years in 2013. In the subgroup analysis, there were more males than females with adolescence acne (61.3% vs. 38.8%, P < 0.01) and more females with post adolescence acne (69.0% vs. 31.0%, P < 0.01). Thirty-four (40.5%) post adolescence acne patients had acne from adolescence persisting into adulthood. Comedonal acne was more prevalent in the adolescence acne patients (58.8% vs. 40.5%, P = 0.019), whereas cystic acne was more prevalent in post-adolescence patients (18.1% vs. 7.5%, P = 0.044). Systemic retinoids were more often used for treatment in the adolescence acne patients than post-adolescence acne patients (23.8% vs. 10.7%, P = 0.027). CONCLUSION: Acne predominantly affects adolescents but post-adolescence acne is not uncommon. For post-adolescence acne, females predominate over males. Inflammatory and cystic acne tends to be more predominant in post-adolescence acne patients, whereas comedonal acne is more often seen in adolescence acne patients. PMID- 27400810 TI - [CO2 laser treatment of palpebral syringoma]. PMID- 27400811 TI - [Superficial pemphigus: Histological image of neutrophilic spongiosis]. PMID- 27400812 TI - [Vulvar syringoma]. PMID- 27400813 TI - Editorial overview: Sequences and topology: Protein function - synthesizing information from sequence, structure and disorder. PMID- 27400814 TI - Aortic pulse wave velocity predicts incident cardiovascular events in patients with type 2 diabetes treated in primary care. AB - AIMS: The aim was to evaluate the predictive value of aortic pulse wave velocity (aPWV) on incident cardiovascular events in patients with type 2 diabetes without previous cardiovascular disease who were treated in primary care, after adjustment for traditional risk factors. METHODS: We measured aPWV in 627 patients who participated in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) and who did not have previously known myocardial infarction or stroke. The outcome variable was a composite endpoint consisting of cardiovascular mortality, hospitalization for myocardial infarction and hospitalization for stroke. RESULTS: During a median follow-up time of almost eight years, the unadjusted HR per each increment of aPWV by 1m/s was 1.239 (95% CI 1.114-1.379, P<0.001) for the primary endpoint. Following adjustments for age, sex, diabetes duration, office systolic blood pressure, resting heart rate, total cholesterol, HbA1c, estimated glomerular filtration rate and smoking status, the adjusted hazard ratio was 1.142 (95% CI 1.003-1.301, P=0.044). CONCLUSIONS: In primary preventive patients with type 2 diabetes treated in primary care, aPWV predicted a composite outcome of incident cardiovascular events independently of diabetes-specific and traditional risk factors. PMID- 27400815 TI - Money Matters: Recommendations for Financial Stress Research in Occupational Health Psychology. AB - Money is arguably the most important resource derived from work and the most important source of stress for contemporary employees. A substantial body of research supports the relationship between access to financial resources and health and well-being, both at individual and aggregated (e.g. national) levels of analysis. Yet, surprisingly little occupational health psychology research has paid attention to financial issues experienced specifically by those in the labour force. With these issues in mind, the overarching goal of the present paper was to address conceptual and measurement issues in the study of objective and subjective aspects of financial stress and review several assessment options available to occupational health psychology researchers for both aspects of financial stress. Where appropriate, we offer guidance to researchers about choices among various financial stress measures and identify issues that require further research attention. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27400816 TI - Sandwich consumption in relation to daily dietary intake and diet quality among US adults, 2003-2012. AB - OBJECTIVES: About one half of the US adult population consumed one or more sandwiches on any given day. Sandwich consumption may profoundly influence people's calorie intake and diet quality. However, few studies have investigated the nutritional impact of sandwich consumption at the national level. We examined sandwich consumption in relation to daily dietary intake and diet quality among US adults. STUDY DESIGN: Retrospective data analysis. METHODS: Nationally representative sample consisting of 27,075 adults 18 years of age and above came from the National Health and Nutrition Examination Survey (NHANES) 2003-2012 waves. Sandwich consumption was identified based on the What We Eat in America Food Category and the NHANES diet combination code. First-difference estimator addressed confounding bias from time-invariant unobservables (e.g. eating habits, taste preferences) by using within-individual variations in sandwich consumption between two non-consecutive 24-h dietary recalls. RESULTS: During 2003-2012, approximately 53.2% of US adults consumed sandwiches on any given day. Among sandwich consumers, nearly a quarter of daily total calorie intake and about a third of total fat, saturated fat, cholesterol, and sodium intake came from sandwich consumption. Men, non-Hispanic whites, young and middle-aged adults, people with higher income, and overweight/obese adults were more likely to consume sandwiches. Among those who consumed sandwiches on either but not both of the two dietary recall days, in comparison to no sandwich consumption, sandwich consumption on a dietary recall day was associated with an increase in daily intake of total energy by 98.7 kcal, total fat 6.8 g, and sodium 267.9 mg (P value < 0.001). Statistically significant but relatively small differences were also found for other nutrients and food groups-sandwich consumption was associated with an increase in daily intake of sugar by 3.0 g (P-value < 0.01) and saturated fat 2.5 g (P-value < 0.001), a decrease in daily intake of vegetables by 8.4 g (P-value < 0.01), fruit 4.5 g (P-value < 0.05), and fibre 0.8 g (P-value < 0.001), and a decrease in the Healthy Eating Index-2010 score by 1.6 points (P-value < 0.001). CONCLUSIONS: Consumers should prudently evaluate the calorie/nutrient content of sandwich in order to make healthier dietary choices. PMID- 27400817 TI - Compressed CO2 mediated synthesis of bifunctional periodic mesoporous organosilicas with tunable porosity. AB - A facile and green method is proposed for the fabrication of bifunctional periodic mesoporous organosilicas (PMOs) using compressed CO2. PMID- 27400818 TI - The vascular cooling effect in hepatic multipolar radiofrequency ablation leads to incomplete ablation ex vivo. AB - PURPOSE: Major limitations of conventional RFA are vascular cooling effects. However, vascular cooling effects are supposed to be less pronounced in multipolar RFA. The objective of this ex vivo study was a systematic evaluation of the vascular cooling effects in multipolar RFA. MATERIALS AND METHODS: Multipolar RFA with three bipolar RFA applicators was performed ex vivo in porcine liver (applicator distance 20 mm, energy input 40 kJ). A saline-perfused glass tube ('vessel') was placed parallel to the applicators in order to simulate a natural liver vessel. Five applicator-to-vessel geometries were tested. A liquid-filled glass tube without perfusion was used as a dry run. Ablations were orthogonally cut to the applicators at a defined height. Cooling effects were analysed qualitatively and quantitatively along these cross sectional areas. RESULTS: Thirty-six ablations were performed. A cooling effect could be seen in all ablations with perfused vessels compared to the dry run. While this cooling effect did not have any influence on the ablation areas (859-1072 mm(2) versus 958 mm(2) in the dry run, p > 0.05), it had a distinctive impact on ablation shape. A vascular cooling effect could be observed in all ablations with perfusion directly around the vessel independent of the applicator position compared to the dry run (p < 0.01). CONCLUSIONS: A vascular cooling effect occurred in all multipolar RFA with simulated liver vessels ex vivo independent of the applicator-to-vessel geometry. While the cooling effect did not influence the total ablation area, it had a distinctive impact on the ablation shape. PMID- 27400819 TI - Short message service (SMS) texting as a method of communication during on call: prevalence and experience of medical staff in a large acute NHS Trust in the UK. AB - With the widespread use of smartphones, text messaging has become an accepted form of communication for both social and professional use in medicine. To our knowledge no published studies have assessed the prevalence and use of short message service (SMS) texting by doctors on call. We have used an online questionnaire to seek information from doctors in a large NHS Trust in the UK about their use of texting while on call, what they use it for, and whether they send images relevant to patients' care. We received 302 responses (43% response rate), of whom 166 (55%) used SMS while on call. There was a significant association between SMS and age group (p=0.005), with the 20-30-year-old group using it much more than the other age groups. Doctors in the surgical specialties used it significantly less than those in other speciality groups (p<0 .001). Texting while on call was deemed to be safe and reliable (p<0.001). Eighteen clinicians (11%) admitted to routinely sending images of patients by text, despite some being identifiable. Texting was mainly used to update colleagues on patients' progress and give information about times of ward rounds and meetings. With the increasing use of texting in healthcare, much of which seems to be unregulated, further work and detailed guidance is required on what information may be given to ensure confidentiality and that SMS is a safe and acceptable method of communication to use when on call. PMID- 27400820 TI - Freezing the Nonclassical Crystal Growth of a Coordination Polymer Using Controlled Dynamic Gradients. AB - A methodology that can be efficiently used to synthesize, isolate, and study out of-equilibrium crystal structures employing controlled and diffusion-limited microfluidic environments is demonstrated. Unlike studies conducted with conventional mixing procedures in a flask, it is proven experimentally and with numerical simulations that microfluidic technologies can undoubtedly fine-tune reaction times and reagents concentration profiles; factors that enable out-of equilibrium crystal forms to be obtained. PMID- 27400821 TI - Psychogenic Nonepileptic Seizures: Diagnosis, Management, and Bioethics. AB - BACKGROUND: The diagnosis and management of psychogenic nonepileptic seizures (PNES) is often challenging and fraught with discord and disagreement between patients, parents, and physicians. Furthermore, there are ethical challenges when making the diagnosis, communicating this information, and instituting management. METHODS: We reviewed the current body of knowledge regarding the characteristic differences between epileptic seizures and PNES, and the high incidence of psychiatric comorbidities. An ethical analysis was made of diagnosis and management based on ethical principles, virtue ethics, and the social contract that health professionals have with patients. RESULTS: Key distinctions between PNES and epilepsy lie in both patient and seizure characteristics. Long duration, eye closure, asynchronous movements, frequent recurrence in the same context, intra-ictal awareness, and lack of post ictal state are useful in helping establish the diagnosis. Psychiatric comorbidities, history of abuse, cognitive impairment, and multiple non specific somatic complaints are some salient patient features that should increase suspicion for the diagnosis of PNES. However, definitive diagnosis rests on capturing the events on video EEG. CONCLUSION: Effective diagnosis and management of PNES requires the use of video EEG and an early collaborative approach between pediatricians, neurologists, psychiatrists, nursing staff, and other professional colleagues. Ethical questions that may arise should be addressed with the virtues of competence, courage, compassion, prudence, and honesty; and the principles of respect beneficence, and the avoidance of unnecessary harm. PMID- 27400822 TI - Childhood-Onset Multifocal Motor Neuropathy With Immunoglobulin M Antibodies to Gangliosides GM1 and GM2: A Case Report and Review of the Literature. AB - Multifocal motor neuropathy is a rare immune-mediated neuropathy characterized by progressive asymmetric weakness and atrophy without sensory abnormalities. Although disease onset is usually in adulthood, a few childhood-onset cases have been reported. Here, we report the case of an 8-year-old boy with multifocal motor neuropathy who presented with a slowly progressive left and distal upper limb weakness without sensory loss. The initial high-dose intravenous immunoglobulin treatment significantly improved left upper limb muscle weakness. Continued monthly intravenous immunoglobulin treatment gradually improved muscle strength for several months initially. While the muscle strength decreased slightly after 8 months of therapy, it was better than that before intravenous immunoglobulin treatment. One year and eight months after the initiation of treatment, serum testing for IgM antibodies to gangliosides, GM1 and GM2, was negative. This is the first pediatric report of the serum IgM autoantibodies positive to GM1 and GM2. The clinical course is similar to that of partial intravenous immunoglobulin responders among patients with adulthood-onset multifocal motor neuropathy. Since the symptoms plateaued after the initial intravenous immunoglobulin therapy, prognosis appears to be determined by the patient's initial response to intravenous immunoglobulin treatment. PMID- 27400823 TI - Six- and twelve-month documented removal rates among women electing postpartum inpatient compared to delayed or interval contraceptive implant insertions after Medicaid payment reform. AB - OBJECTIVE: This study aims to document 6- and 12-month removal rates for women receiving the contraceptive implant inpatient postpartum versus those receiving the same contraceptive method during an outpatient visit, in a setting where postpartum inpatient long-acting reversible contraceptive (LARC) services (devices plus provider insertion costs) are reimbursed by Medicaid. STUDY DESIGN: We conducted a retrospective cohort study among Medicaid-enrolled women using medical record review for all women receiving the etonogestrel implant between July 1, 2007 and June 30, 2014. We compared the percentage of women with the implant removed at 6 and 12 months as well as reasons for early removal, for inpatient postpartum implant insertions vs. delayed postpartum or interval outpatient implant insertions. RESULTS: A total of 4% of women (34/776 insertions) had documented implant removal within 6 months post-insertion, with no difference between postpartum inpatient and outpatient (delayed postpartum or interval). A total of 12% (62/518 insertions) of women had documented implant removal within 12 months. A lower percentage of women with postpartum inpatient insertions had the implant removed at 12 months post-insertion, compared to outpatient insertions (7% vs. 14%, p=.04). After controlling for age, parity, race and body mass index, women with postpartum inpatient insertions were less likely to have the implant removed within 12 months (OR=0.44, 95% CI 0.20-0.97). The most commonly stated reason for removal was abnormal uterine bleeding, regardless of insertion timing. CONCLUSION: In a setting with a Medicaid policy that covers postpartum inpatient LARC insertion, a low percentage of women who received an implant immediately postpartum had it removed within 1 year of insertion. IMPLICATIONS: A Medicaid payment policy that removes institutional barriers to offering postpartum inpatient contraceptive implants to women free-of charge may facilitate meeting women's desires and intentions to delay subsequent pregnancy, as evidenced by low removal rates up to 12 months post-insertion. Further research with women is needed to assess how these services meet their postpartum contraceptive needs and desires to postpone or prevent subsequent pregnancy. PMID- 27400824 TI - Unmet counselling need amongst women accessing an induced abortion service in KwaZulu-Natal, South Africa. AB - OBJECTIVES: Provision of objective, evidence-based counselling in the context of induced abortion services is considered global good practise. However, there is limited understanding over the counselling needs of women accessing abortion services, particularly in sub-Saharan Africa. This study aimed to explore the content and quality of pre-abortion counselling amongst women accessing an abortion service in South Africa as well as client experience of the counselling process. Perceptions of nurse counsellors were also sought. STUDY DESIGN: This was a mixed methods study conducted at a Choice of Termination of Pregnancy clinic based at a district level hospital in KwaZulu-Natal, South Africa. Sixty women requesting an abortion were interviewed via a semi-structured questionnaire. In-depth interviews were conducted with four nurses who provided pre-abortion counselling at the clinic. Interviews were coded for emergent themes and categories. RESULTS: Clinic nurses had widely variable counselling training and experience, ranging from less than 2 months to 8 years, but all clients reported that they had been treated with respect at their counselling session. The group-based counselling format and biomedical and health promotion content did not accommodate clients' differential counselling needs, which included requests for support from women experiencing intimate partner violence (IPV). There was limited provider awareness of client's additional counselling needs. CONCLUSION: Abortion counselling services should be tailored to clients' differential counselling needs. Group-based counselling followed by optional one on-one counselling sessions is one possible strategy to address unmet client need in South Africa. Provision of abortion provider training in IPV is recommended as well as establishment of referral pathways for women experiencing IPV. IMPLICATIONS: Paying attention to the differential counselling needs of women seeking an abortion should be a key component to the provision of abortion services. In this way, abortion services can provide a gateway to additional support for women living in violent relationships and/or other adverse social circumstances. PMID- 27400825 TI - National network television news coverage of contraception - a content analysis. AB - OBJECTIVE: The objective was to describe and analyze national network television news framing of contraception, recognizing that onscreen news can influence the public's knowledge and beliefs. STUDY DESIGN: We used the Vanderbilt Television News Archives and LexisNexis Database to obtain video and print transcripts of all relevant national network television news segments covering contraception from January 2010 to June 2014. We conducted a content analysis of 116 TV news segments covering contraception during the rollout of the Affordable Care Act. Segments were quantitatively coded for contraceptive methods covered, story sources used, and inclusion of medical and nonmedical content (intercoder reliability using Krippendorf's alpha ranged 0.6-1 for coded categories). RESULTS: Most (55%) news stories focused on contraception in general rather than specific methods. The most effective contraceptive methods were rarely discussed (implant, 1%; intrauterine device, 4%). The most frequently used sources were political figures (40%), advocates (25%), the general public (25%) and Catholic Church leaders (16%); medical professionals (11%) and health researchers (4%) appeared in a minority of stories. A minority of stories (31%) featured medical content. CONCLUSIONS: National network news coverage of contraception frequently focuses on contraception in political and social terms and uses nonmedical figures such as politicians and church leaders as sources. This focus deemphasizes the public health aspect of contraception, leading medical professionals and health content to be rarely featured. IMPLICATIONS: Media coverage of contraception may influence patients' views about contraception. Understanding the content, sources and medical accuracy of current media portrayals of contraception may enable health care professionals to dispel popular misperceptions. PMID- 27400826 TI - A review of toxic epidermal necrolysis management in Japan. AB - Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction characterized by necrosis of the epidermis. Its incidence is approximately 1 per million a year and average mortality rate is high at 25-50%. TEN has a flu-like prodrome, followed by atypical, targetoid erythematous or purpuric macules on the skin. These macules coalesce to form flaccid blisters that slough off as areas of epidermal necrosis. Drugs such as allopurinol, sulfonamides, and carbamazepine are the most common causes. The human leukocyte antigen (HLA)-B*15:02 in Asians being administered carbamazepine and the HLA-B*58:01 antigen in patients of all ethnicities being administered allopurinol are known to be high-risk factors. Rapid diagnosis, discontinuation of the causative drug, and supportive treatment are essential for better prognosis and improvement of sequelae. Till now, systemic corticosteroids and intravenous immunoglobulins have been used as the most common active interventions; however, no gold standard has been established. In Japan, physicians follow a unique diagnostic criteria and treatment guideline to improve the diagnosis rate and streamline treatments. This may be a contributing factor for the lower mortality rate (14.3%). The efficacy of systemic corticosteroids, immunoglobulins, and plasmapheresis may have been beneficial as well. In Japan, TEN is defined as an epidermal detachment of over 10% of the body surface area (BSA), while the globally accepted definition established by Bastuji-Garin describes it as an epidermal detachment of over 30% of the BSA. In Japanese individuals, HLA-A*02:06, HLA-A*02:07, HLA-A*31:01 and HLA-B*51:01 may be linked to higher risks of TEN. PMID- 27400827 TI - Detection of LacZ-Positive Cells in Living Tissue with Single-Cell Resolution. AB - The LacZ gene, which encodes Escherichia coli beta-galactosidase, is widely used as a marker for cells with targeted gene expression or disruption. However, it has been difficult to detect lacZ-positive cells in living organisms or tissues at single-cell resolution, limiting the utility of existing lacZ reporters. Herein we present a newly developed fluorogenic beta-galactosidase substrate suitable for labeling live cells in culture, as well as in living tissues. This precisely functionalized fluorescent probe exhibited dramatic activation of fluorescence upon reaction with the enzyme, remained inside cells by anchoring itself to intracellular proteins, and provided single-cell resolution. Neurons labeled with this probe preserved spontaneous firing, which was enhanced by application of ligands of receptors expressed in the cells, suggesting that this probe would be applicable to investigate functions of targeted cells in living tissues and organisms. PMID- 27400828 TI - Nurses' perceptions of mental healthcare in primary-care settings in Kenya. AB - Kenya maintains an extraordinary treatment gap for mental health services because the need for and availability of mental health services are extraordinarily misaligned. One way to narrow the treatment gap is task-sharing, where specialists rationally distribute tasks across the health system, with many responsibilities falling upon frontline health workers, including nurses. Yet, little is known about how nurses perceive task-sharing mental health services. This article investigates nurses' perceptions of mental healthcare delivery within primary-care settings in Kenya. We conducted a cross-sectional study of 60 nurses from a public urban (n = 20), private urban (n = 20), and public rural (n = 20) hospitals. Nurses participated in a one-hour interview about their perceptions of mental healthcare delivery. Nurses viewed mental health services as a priority and believed integrating it into a basic package of primary care would protect it from competing health priorities, financial barriers, stigma, and social problems. Many nurses believed that integrating mental healthcare into primary care was acceptable and feasible, but low levels of knowledge of healthcare providers, especially in rural areas, and few specialists, would be barriers. These data underscore the need for task-sharing mental health services into existing primary healthcare in Kenya. PMID- 27400829 TI - Huperzine A protects sepsis associated encephalopathy by promoting the deficient cholinergic nervous function. AB - Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action. PMID- 27400830 TI - Shifting the balance: conceptualising empowerment in individuals with spinal cord injury. AB - Empowerment is believed to be an essential element in self-management of disease and the promotion of self-efficacy, and can be defined as the ability of individuals to increase control over aspects of their lives. In contrast, powerlessness in individuals with chronic illness can occur when they perceive that they lack the capacity, authority or resources to affect an outcome. Individuals with spinal cord injuries (SCIs) are at risk for powerlessness and have the potential to become empowered, but these concepts have not been explored within their context. The purpose of this study was to explore how individuals with SCI enact the empowerment process using Lord's (1991) process of empowerment framework. This study used a secondary analysis of a data set obtained from a mixed methods study exploring access to health and social care for 23 persons with SCI in Saskatchewan, Canada. The primary study data were collected from September 2012 to January 2013. The secondary analysis of data utilised a deductive thematic analysis approach and findings were conceptualised and applied to a model that represents the shift in balance between powerlessness and empowerment in individuals with SCI. PMID- 27400831 TI - Loss-of-function of Arabidopsis receptor-like kinase BIR1 activates cell death and defense responses mediated by BAK1 and SOBIR1. AB - The Arabidopsis receptor-like kinase (RLK) BIR1 (BAK1-INTERACTING RECEPTOR-LIKE KINASE 1) functions as a negative regulator of plant immunity. Previous work showed that loss-of-function of BIR1 leads to constitutive activation of cell death and defense responses. These autoimmune phenotypes are partially dependent on another RLK, SOBIR1. In order to identify additional components involved in the BIR1-regulated plant defense signaling pathway, a suppressor screen was carried out in the bir1-1 pad4-1 mutant background. Mutations in the suppressor mutants were identified by genetic mapping and re-sequencing of the mutant genomes. A number of suppressor mutants were found to carry mutations in an additional RLK, BAK1, indicating that BAK1 is required for activation of cell death and defense responses in bir1-1. Co-immunoprecipitation analysis revealed that BAK1 and SOBIR1 associate with each other in planta when the function of BIR1 is compromised. Although BAK1 was previously characterized as a negative regulator of cell death, our study highlights a novel role of BAK1 in promoting cell death and defense responses in conjunction with SOBIR1. PMID- 27400832 TI - Metabonomic alterations from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma facilitate the identification of biomarkers in serum for early diagnosis of pancreatic cancer. AB - Pancreatic cancer is a highly malignant disease with a poor prognosis and it is essential to diagnose and treat the disease at an early stage. The aim of this study was to understand the underlying biochemical mechanisms of pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and to identify potential serum biomarkers for early detection of pancreatic cancer. 7,12-Dimethylbenz(a)anthracene (DMBA)-induced PanIN and PDAC rat models were established and the serum samples were collected. The serum samples were measured using (1)H nuclear magnetic resonance (NMR) spectroscopy and analyzed by chemometric methods including principal component analysis (PCA) and (orthogonal) partial least squares discriminant analysis ((O)PLS-DA). The related biochemical pathways were derived from KEGG analysis of the significantly different metabolites. As results, some serum metabolites demonstrated alarming metabolic changes in the precursor lesion of pancreatic cancer (PanIN-2 in this study). These changes involved elevated levels of ketone compounds including 3 hydroxybutyrate, acetoacetate, and acetone, some amino acids including asparagine, glutamate, threonine, and phenylalanine, glycoproteins and lipoproteins including N-acetylglycoprotein, LDL and VLDL, and some metabolites that have been shown to contribute to mutagenicity and cancer promotion such as deoxyguanosine and cytidine. More metabolites were shown to be significantly different between PanIN and PDAC, suggesting that a more complex set of changes occurs from noninvasive precursor lesion to invasive cancer. The serum metabonomic changes of rats with PanIN and PDAC may extend our understanding of pancreatic molecular pathogenesis, and the metabolic variations from PanIN to PDAC will be helpful to understand evolution processes of the pancreatic disease. NMR-based metabonomic analysis of animal models will be beneficial for the human study and will be helpful for the early detection of pancreatic cancer. PMID- 27400833 TI - Development of reverse transcription loop-mediated isothermal amplification assay as a simple detection method of Chrysanthemum stem necrosis virus in chrysanthemum and tomato. AB - For a simple and rapid detection of Chrysanthemum stem necrosis virus (CSNV) from chrysanthemum and tomato, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed. A primer set designed to the genome sequences of CSNV worked most efficiently at 63 degrees C and could detect CSNV RNA within 12min by fluorescence monitoring using an isothermal DNA amplification and fluorescence detection device. The result of a specificity test using seven other viruses and one viroid-infectable chrysanthemum or tomato showed that the assay could amplify CSNV specifically, and a sensitivity comparison showed that the RT-LAMP assay was as sensitive as the reverse transcriptase polymerase chain reaction. The RT-LAMP assay using crude RNA, extracted simply, could detect CSNV. Overall, the RT-LAMP assay was found to be a simple, specific, convenient, and time-saving method for CSNV detection. PMID- 27400835 TI - A standardized production pipeline for high profile targets from Mycobacterium tuberculosis. AB - PURPOSE: Tuberculosis is still a major threat to global health. New tools and strategies to produce disease-related proteins are quintessential for the development of novel vaccines and diagnostic markers. EXPERIMENTAL DESIGN: To obtain recombinant proteins from Mycobacterium tuberculosis (Mtb) for use in clinical applications, a standardized procedure was developed that includes subcloning, protein expression in Mycobacterium smegmatis and protein purification using chromatography. The potential for the different protein targets to serve as diagnostic markers for tuberculosis was established using multiplex immunoassays. RESULTS: Twelve soluble proteins from Mtb, including one protein complex, were purified to near-homogeneity following recombinant expression in M. smegmatis. Protein purity was assessed both by size exclusion chromatography and MS. Multiplex serological testing of the final protein preparations showed that all but one protein displayed a clear antibody response in serum samples from 278 tuberculosis patients. CONCLUSION AND CLINICAL RELEVANCE: The established workflow comprises a simple, cost-effective, and scalable pipeline for production of soluble proteins from Mtb and can be used to prioritize immunogenic proteins suitable for use as diagnostic markers. PMID- 27400837 TI - Management of the Nasal Valve. AB - The nasal valve is an important consideration in patients presenting with nasal obstruction. Controversy exists regarding the anatomy, terminology, evaluation, and management of the nasal valve. Innumerable techniques with variable effects have been described in the literature. The evidence qualifying these techniques has been plentiful, though often lacking in quality. This article reviews the controversial aspects of nasal valve management applying the best available evidence to help clarify potential areas of confusion. Future research using standardized definitions, consistent methodologies, and validated outcome measures are necessary to improve the quality of evidence and impact surgical decision-making. PMID- 27400836 TI - Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifests and premanifest huntington's disease. AB - Huntington's disease (HD) is a genetic neurological disorder resulting in cognitive and motor impairments. We evaluated the longitudinal changes of functional connectivity in sensorimotor, associative and limbic cortico-basal ganglia networks. We acquired structural MRI and resting-state fMRI in three visits one year apart, in 18 adult HD patients, 24 asymptomatic mutation carriers (preHD) and 18 gender- and age-matched healthy volunteers from the TRACK-HD study. We inferred topological changes in functional connectivity between 182 regions within cortico-basal ganglia networks using graph theory measures. We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks. Changes in graph theory metrics (L, k, C and bc) correlated with four clinical and cognitive measures (symbol digit modalities test, Stroop, Burden and UHDRS). There were no changes in graph theory metrics across sessions, which suggests that these measures are not reliable biomarkers of longitudinal changes in HD. preHD is characterized by progressive decreasing hub organization, and these changes aggravate in HD patients with changes in local metrics. HD is characterized by progressive changes in global network interconnectivity, whose network topology becomes more random over time. Hum Brain Mapp 37:4112-4128, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27400838 TI - Controversies in Parotid Defect Reconstruction. AB - Reconstruction of the parotid defect is a complex topic that encompasses restoration of both facial form and function. The reconstructive surgeon must consider facial contour, avoidance of Frey syndrome, skin coverage, tumor surveillance, potential adjuvant therapy, and facial reanimation when addressing parotid defects. With each defect there are several options within the reconstructive ladder, creating controversies regarding optimal management. This article describes surgical approaches to reconstruction of parotid defects, highlighting areas of controversy. PMID- 27400839 TI - Septorhinoplasty in the Pediatric Patient. AB - Pediatric septorhinoplasty has been an area of controversy because early surgical intervention can prevent normal growth. There are certain conditions where early correction of the nose is indicated, such as in cleft lip nasal deformities, severe traumatic deformities, and congenital nasal lesions. Animal and clinical studies have been helpful in elucidating certain areas of the nose that are potential growth zones that should be left undisturbed when performing nasal surgeries on pediatric patients. We discuss the timing, indications, and surgical technique in pediatric septorhinoplasty. PMID- 27400841 TI - Evidence-based Medicine in Facial Plastic Surgery: Current State and Future Directions. AB - Evidence-based medicine (EBM) encompasses the evaluation and application of best available evidence, incorporation of clinical experience, and emphasis on patient preference and values. Different scales are used to rate levels of evidence. Translating available data for interventions to clinical practice guidelines requires an assessment of both the quality of evidence and the strength of recommendation. Essential to the practice of EBM is evaluating the effectiveness of an intervention through outcome measures. This article discusses principles essential to EBM, resources commonly used in EBM practice, and the strengths and limitations of EBM in facial plastic and reconstructive surgery. PMID- 27400840 TI - Controversies in the Management of Patients with Cleft Lip and Palate. AB - Cleft lip and palate is one of the most common congenital anomalies. For many years, surgeons have been attempting to reduce the severity of the deformity before the surgical repair to achieve a better outcome. The nasoalveolar molding technique uses acrylic nasal stents attached to the vestibular shield of an oral molding plate to mold the nasal alar cartilages into a more normal form and position during the presurgical period. Proponents of nasoalveolar molding claim several benefits, including improved aesthetic outcome, reduced overall costs, and a psychosocial benefit to the family. Research on these outcomes is not conclusive. PMID- 27400842 TI - Controversies in Contemporary Facial Reanimation. AB - Facial palsy is a devastating condition with profound functional, aesthetic, and psychosocial implications. Although the complexity of facial expression and intricate synergy of facial mimetic muscles are difficult to restore, the goal of management is to reestablish facial symmetry and movement. Facial reanimation surgery requires an individualized treatment approach based on the cause, pattern, and duration of facial palsy while considering patient age, comorbidities, motivation, and goals. Contemporary reconstructive options include a spectrum of static and dynamic procedures. Controversies in the evaluation of patients with facial palsy, timing of intervention, and management decisions for dynamic smile reanimation are discussed. PMID- 27400843 TI - Controversies in the Management of the Trauma Patient. AB - Facial trauma is a significant cause of morbidity in the United States. Despite the large volume of trauma surgeries at most academic institutions, there is still controversy regarding management of many traumatic injuries. The literature lacks clear-cut best practices for most fractures. In orbital trauma, there is debate about the optimal timing of repair, preferred biomaterial to be used, and the utility of evaluation afterward with intraoperative computed tomographic scan. In repair of mandible fractures, there is debate regarding open versus closed reduction of subcondylar fractures, or alternatively, endoscopic repair. PMID- 27400845 TI - Measuring Nasal Obstruction. AB - The nose and the nasal airway is highly complex with intricate 3-dimensional anatomy, with multiple functions in respiration and filtration of the respired air. Nasal airway obstruction (NAO) is a complex problem with no clearly defined "gold-standard" in measurement. There are 3 tools for the measurement of NAO: patient-derived measurements, physician-observed measurements, and objective measurements. We continue to work towards finding a link between subjective and objective nasal obstruction. The field of evaluation and surgical treatment for NAO has grown tremendously in the past 4-5 decades and will continue to grow as we learn more about the pathophysiology and treatment of nasal obstruction. PMID- 27400846 TI - Primary Rhinoplasty. AB - Rhinoplasty is inherently a difficult procedure given the complexity of its structure and the functional and aesthetic impact of this anatomy. This report explores some of the remaining questions regarding the use of spreader grafts and autospreader flaps in the management of the middle vault in rhinoplasty, the performance of the open approach versus the endonasal rhinoplasty approach, corrective rhinoplasty in the younger patient, the use of the rib and other cartilage donor sites for grafting in rhinoplasty, and the use of filler materials in rhinoplasty. PMID- 27400844 TI - Postoperative Controversies in the Management of Free Flap Surgery in the Head and Neck. AB - Free tissue transfer is the gold standard for reconstructing head and neck defects. Free flap success approaches 95% in centers with experience, affording unparalleled ability to restore form and function in cancer, trauma, or other major composite tissue loss. It is critical to manage the perioperative variables that predict success; several areas of controversy have not yet reached consensus. This review focuses on postoperative anticoagulation, fluid management, and flap monitoring methods. These areas of controversy potentially influence flap survival. We review published practices considered within the standard of care, why controversy remains, and future directions to reach standardization. PMID- 27400847 TI - Controversies in Revision Rhinoplasty. AB - Revision rhinoplasty is a complex operation with many variables that may influence the final esthetic and functional outcome of the procedure. Cartilage forms the structural framework of the lower two-thirds of nose and is essential for long-term support and maintenance of a patent nasal airway. The use of autologous cartilage grafting is the primary source of this material, limited by donor site quantity, quality, and harvest morbidity. Alloplastic materials, solid and injectable, are often used for augmentation purposes and may have devastating consequences. This article discusses past and current treatment concepts for various nasal deformities using available autologous grafting techniques. PMID- 27400848 TI - Antibiotic Use in Facial Plastic Surgery. AB - Prophylactic antibiotic use in facial plastic surgery is a highly controversial topic primarily due to the lack of evidence in support of or against antibiotic use. In this section the authors present the available literature on the most commonly performed procedures within facial plastic surgery in an attempt to see if the data support or contradict the need for antibiotic prophylaxis in facial plastic surgery. PMID- 27400849 TI - Facelift Controversies. AB - The primary purpose of the facelift is to restore the shape, volume, and contours of the youthful face. Facelift surgery has evolved over the years into multiple techniques to accomplish the same results. This article discusses the common controversies in facelift surgery and evaluates the best available evidence to guide surgical decision-making. In regard to the salient question of whether there is a "best" technique, the literature suggests that the options are generally equal in efficacy. This highlights the need for high-quality research with standardized preoperative assessment and evaluation of postoperative results to better assess outcomes. PMID- 27400850 TI - Facial Transplantation. AB - Reconstruction of severe facial deformities poses a unique surgical challenge: restoring the aesthetic form and function of the face. Facial transplantation has emerged over the last decade as an option for reconstruction of these defects in carefully selected patients. As the world experience with facial transplantation grows, debate remains regarding whether such a highly technical, resource intensive procedure is warranted, all to improve quality of life but not necessarily prolong it. This article reviews the current state of facial transplantation with focus on the current controversies and challenges, with particular attention to issues of technique, immunology, and ethics. PMID- 27400851 TI - Injectables in the Nose: Facts and Controversies. AB - Nasal injectables and surface treatments alter the appearance of the nose both primarily and following nasal surgery. Fillers such as hyaluronic acids, calcium hydroxyapatite, and fat have a variety of advantages and disadvantages in eliminating small asymmetries postrhinoplasty. All nasal injectables have rare but severe ocular and cerebral ischemic complications. The injection of steroids following nasal reconstruction has a role in preventing supratip swelling and can improve the appearance of grafts to the nose. Resurfacing techniques reduce the appearance of autotransplanted grafts to the nose; there is little controversy about their benefit but surgeon preference for timing is varied. PMID- 27400852 TI - Facial Reconstructive Controversies. PMID- 27400853 TI - Serum alpha-fetoprotein concentration in extremely low-birthweight infants. AB - BACKGROUND: Extremely low-birthweight infants (ELBWI) are at greater risk of developing hepatoblastoma than are normal-weight infants. Serum alpha-fetoprotein (AFP) plays an important role as a tumor marker in the diagnosis of hepatoblastoma, therefore the aim of this study was to determine the changes in serum AFP concentration after birth in ELBWI. METHODS: Data were obtained for infants born between January 2005 and March 2008 with birthweight <1000 g who were followed up at Gunma Children's Medical Center with clinical examinations, including monitoring of the development of hepatoblastoma. The relationship between serum AFP concentration and age was analyzed up to 730 days after birth. RESULTS: Overall, 95 serum AFP measurements were obtained from 23 infants 30-730 days of age, with gestational age 24-32 weeks, and birthweight 498-982 g. Log10 (AFP [ng/mL]) was significantly correlated with log10 (age [days]) (r = -0.961, P = 0.000, n = 95), with the following regression formula: log10 (AFP [ng/mL]) = 11.063 - 3.752 log10 (age [days]) (adjusted R2 = 0.923, n = 95). The standard error of the estimate, mean log10 (age [days]), and the sum of squares for log10 (age [days]) were 0.363, 2.503, and 10.579, respectively. CONCLUSIONS: A correlation was found between serum AFP concentration and age in ELBWI, and the 95%CI of serum AFP concentration was determined for ELBWI up to 2 years after birth. PMID- 27400854 TI - Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. AB - Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics. PMID- 27400855 TI - HCN-channel dendritic targeting requires bipartite interaction with TRIP8b and regulates antidepressant-like behavioral effects. AB - Major depressive disorder (MDD) is a prevalent psychiatric condition with limited therapeutic options beyond monoaminergic therapies. Although effective in some individuals, many patients fail to respond adequately to existing treatments, and new pharmacologic targets are needed. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate excitability in neurons, and blocking HCN channel function has been proposed as a novel antidepressant strategy. However, systemic blockade of HCN channels produces cardiac effects that limit this approach. Knockout (KO) of the brain-specific HCN-channel auxiliary subunit tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) also produces antidepressant-like behavioral effects and suggests that inhibiting TRIP8b function could produce antidepressant-like effects without affecting the heart. We examined the structural basis of TRIP8b-mediated HCN-channel trafficking and its relationship with antidepressant-like behavior using a viral rescue approach in TRIP8b KO mice. We found that restoring TRIP8b to the hippocampus was sufficient to reverse the impaired HCN-channel trafficking and antidepressant-like behavioral effects caused by TRIP8b KO. Moreover, we found that hippocampal expression of a mutated version of TRIP8b further impaired HCN channel trafficking and increased the antidepressant-like behavioral phenotype of TRIP8b KO mice. Thus, modulating the TRIP8b-HCN interaction bidirectionally influences channel trafficking and antidepressant-like behavior. Overall, our work suggests that small-molecule inhibitors of the interaction between TRIP8b and HCN should produce antidepressant-like behaviors and could represent a new paradigm for the treatment of MDD. PMID- 27400858 TI - ERalpha dimerization: a key factor for the weak estrogenic activity of an ERalpha modulator unable to compete with estradiol in binding assays. AB - Estrothiazine (ESTZ) is a weak estrogen sharing structural similarities with coumestrol. ESTZ failed to compete with [3H]17beta-estradiol ([3H]17beta-E2) for binding to the estrogen receptor alpha (ERalpha), questioning its ability to interact with the receptor. However, detection by atomic force spectroscopy (AFS) of an ESTZ-induced ERalpha dimerization has eliminated any remaining doubts. The effect of the compound on the proliferation of ERalpha-positive and negative breast cancer cells confirmed the requirement of the receptor. The efficiency of ESTZ in MCF-7 cells was weak without any potency to modify the proliferation profile of estradiol and coumestrol. Growth enhancement was associated with a proteasomal degradation of ERalpha without substantial recruitment of LxxLL coactivators. This may be related to an unusual delay between the acquisition by the receptor of an ERE-binding capacity and the subsequent estrogen-dependent transcription. A complementary ability to enhance TPA-induced AP-1 transcription was observed, even at concentrations insufficient to activate the ERalpha, suggesting a partly independent mechanism. ESTZ also rapidly and transiently activated ERK1/2 likely through membrane estrogenic pathways provoking a reorganization of the actin network. Finally, the systematic absence of biological responses with an ESTZ derivative unable to induce ERalpha dimerization stresses the importance of this step in the action of the compound, as reported for conventional estrogens. In view of the existence of many other ERalpha modulators (endocrine disruptors such as, for example, pesticides, environmental contaminants or phytoestrogens) with extremely weak or similar apparent lack of binding ability, our work may appear as pilot investigation for assessing their mechanism of action. PMID- 27400856 TI - Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia. AB - The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 * 10-8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect. PMID- 27400859 TI - Composition and Interface Engineering of Alloyed MoS2 x Se2(1- x ) Nanotubes for Enhanced Hydrogen Evolution Reaction Activity. AB - Hierarchical MoS2 x Se2(1- x ) nanotubes assembled from several-layered nanosheets featuring tunable chalcogen compositions, expanded interlayer spacing and carbon modification, are synthesized for enhanced electrocatalytic hydrogen evolution reaction (HER). The chalcogen compositions of the MoS2 x Se2(1- x ) nanotubes are controllable by adjusting the selenization temperature and duration while the expanded (002) interlayer spacing varies from 0.98 to 0.68 nm. It is found that the MoS2 x Se2(1- x ) (x = 0.54) nanotubes with expanded interlayer spacing of 0.98 nm exhibit the highest electrocatalytic HER activity with a low onset potential of 101 mV and a Tafel slope of 55 mV dec(-1) . The improved electrocatalytic performance is attributed to the chalcogen composition tuning and the interlayer distance expansion to achieve benefitting hydrogen adsorption energy. The present work suggests a potential way to design advanced HER electrocatalysts through modulating their compositions and interlayer distances. PMID- 27400857 TI - Lithium suppression of tau induces brain iron accumulation and neurodegeneration. AB - Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients. PMID- 27400860 TI - Manganese Superoxide Dismutase Expression Regulates the Switch Between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma. AB - AIM: Epithelial-mesenchymal transition (EMT) is characterized by the acquisition of invasive fibroblast-like morphology by epithelial cells that are highly polarized. EMT is recognized as a crucial mechanism in cancer progression and metastasis. In this study, we sought to assess the involvement of manganese superoxide dismutase (MnSOD) during the switch between epithelial-like and mesenchymal-like phenotypes in breast carcinoma. RESULTS: Analysis of breast carcinomas from The Cancer Genome Atlas database revealed strong positive correlation between tumors' EMT score and the expression of MnSOD. This positive correlation between MnSOD and EMT score was significant and consistent across all breast cancer subtypes. Similarly, a positive correlation of EMT score and MnSOD expression was observed in established cell lines derived from breast cancers exhibiting phenotypes ranging from the most epithelial to the most mesenchymal. Interestingly, using phenotypically distinct breast cancer cell lines, we provide evidence that constitutively high or induced expression of MnSOD promotes the EMT like phenotype by way of a redox milieu predominantly driven by hydrogen peroxide (H2O2). Conversely, gene knockdown of MnSOD results in the reversal of EMT to a mesenchymal-epithelial transition (MET)-like program, which appears to be a function of superoxide (O2(-*))-directed signaling. INNOVATION AND CONCLUSION: These data underscore the involvement of MnSOD in regulating the switch between the EMT and MET-associated phenotype by influencing cellular redox environment via its effect on the intracellular ratio between O2(-*) and H2O2. Strategies to manipulate MnSOD expression and/or the cellular redox milieu vis-a-vis O2( *):H2O2 could have potential therapeutic implications. Antioxid. Redox Signal. 25, 283-299. PMID- 27400861 TI - Tobacco giant loses legal action over Uruguay's tobacco packaging rules. PMID- 27400862 TI - Long term survival with stereotactic ablative radiotherapy (SABR) versus thoracoscopic sublobar lung resection in elderly people: national population based study with propensity matched comparative analysis. AB - OBJECTIVES: To compare cancer specific survival after thoracoscopic sublobar lung resection and stereotactic ablative radiotherapy (SABR) for tumors <=2 cm in size and thoracoscopic resection (sublobar resection or lobectomy) and SABR for tumors <=5 cm in size. DESIGN: National population based retrospective cohort study with propensity matched comparative analysis. SETTING: Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare database in the United States. PARTICIPANTS: Patients aged >=66 with lung cancer undergoing SABR or thoracoscopic lobectomy or sublobar resection from 1 Oct 2007 to 31 June 2012 and followed up to 31 December 2013. MAIN OUTCOME MEASURES: Cancer specific survival after SABR or thoracoscopic surgery for lung cancer. RESULTS: 690 (275 (39.9%) SABR and 415 (60.1%) thoracoscopic sublobar lung resection) and 2967 (714 (24.1%) SABR and 2253 (75.9%) thoracoscopic resection) patients were included in primary and secondary analyses. The average age of the entire cohort was 76. Follow-up of the entire cohort ranged from 0 to 6.25 years, with an average of three years. In the primary analysis of patients with tumors sized <=2 cm, 37 (13.5%) undergoing SABR and 44 (10.6%) undergoing thoracoscopic sublobar resection died from lung cancer, respectively. The cancer specific survival diverged after one year, but in the matched analysis (201 matched patients in each group) there was no significant difference between the groups (SABR v sublobar lung resection mortality: hazard ratio 1.32, 95% confidence interval 0.77 to 2.26; P=0.32). Estimated cancer specific survival at three years after SABR and thoracoscopic sublobar lung resection was 82.6% and 86.4%, respectively. The secondary analysis (643 matched patients in each group) showed that thoracoscopic resection was associated with improved cancer specific survival over SABR in patients with tumors sized <=5 cm (SABR v resection mortality: hazard ratio 2.10, 1.52 to 2.89; P<0.001). Estimated cancer specific survival at three years was 80.0% and 90.3%, respectively. CONCLUSIONS: This propensity matched analysis suggests that patients undergoing thoracoscopic surgical resection, particularly for larger tumors, might have improved cancer specific survival compared with patients undergoing SABR. Despite strategies used in study design and propensity matching analysis, there are inherent limitations to this observational analysis related to confounding, similar to most studies in healthcare of non-surgical technologies compared with surgery. As the adoption of SABR for the treatment of early stage operable lung cancer would be a paradigm shift in lung cancer care, it warrants further thorough evaluation before widespread adoption in practice. PMID- 27400863 TI - Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study. AB - BACKGROUND: Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis. METHOD: We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire. RESULTS: Associations of minor socio environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all p FWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation. CONCLUSIONS: Elevated sensitivity and lack of resilience to socio environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis. PMID- 27400865 TI - The influence of long distance running on sonographic joint and tendon pathology: results from a prospective study with marathon runners. AB - BACKGROUND: The impact of physical exercise on joints and tendons is still a matter of debate. The aim of this study was to investigate with ultrasound the acute effects of extreme physical exercise on knee and ankle joints and their surrounding structures in trained athletes. METHODS: Participants of the Munich marathon were examined by arthrosonography before and after long distance running. Ultrasound assessment included grey scale and power Doppler examination of the knee and talocrural joints with surrounding tendons. Findings consistent with joint effusion, tendon and/or entheseal pathologies were documented. In addition to the ultrasound evaluation, information on training habits and past or present arthralgia or joint swelling was gathered. RESULTS: One Hundred Five runners completed both the pre- and post-excercise ultrasound assessments (baseline and follow-up), resulting in the sonographic evaluation of 420 knee and talocrural joints. At baseline, 105 knee (50) and 38 talocrural joints (18.1) showed effusions, compared to 100 knee (47.6) and 33 talocrural joints (15.7 %) at follow-up. The differences were not significant (p > 0.05 each). Effusion size did not correlate with the timepoint of ultrasound assessment and was independent of covariates such as gender, age or running distance. Hypervascularity of the patellar tendon was detected in 21 cases (10.0 %) at follow-up in contrast to one at baseline (p < 0.001). This observation was more frequent in male than in female participants (p < 0.05). CONCLUSIONS: Acute physical stress is significantly associated with hypervascularity of the patellar tendon. No significant changes of synovial effusion were detected in knee and talocrural joints. PMID- 27400866 TI - In vivo two-photon imaging of striatal neuronal circuits in mice. AB - Imaging studies of the subcortical striatum in vivo have been technically challenging despite its functional importance in movement control and procedural learning. Here, we report a method for imaging striatal neuronal circuits in mice in vivo using two-photon microscopy. Cell bodies and intermingled dendrites of GABAergic neurons labeled with fluorescent proteins were imaged in the dorsal striatum through an imaging window implanted in the overlying cortex. This technique could be highly useful for studying the structure and function of striatal networks at cellular and subcellular resolutions in normal mice, as well as in mouse models of neurological disorders. PMID- 27400864 TI - High prevalence of extended-spectrum beta-lactamase producing enterobacteriaceae among clinical isolates in Burkina Faso. AB - BACKGROUND: Nothing is known about the epidemiology and resistance mechanisms of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in Burkina Faso. The objective of this study was to determine ESBL-PE prevalence and to characterize ESBL genes in Burkina Faso. METHODS: During 2 months (June-July 2014), 1602 clinical samples were sent for bacteriologic investigations to the microbiology laboratories of the tree main hospitals of Burkina Faso. Isolates were identified by mass spectrometry using a matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) BioTyper. Antibiotic susceptibility was tested using the disk diffusion method on Muller-Hinton agar. The different ESBL genes in potential ESBL-producing isolates were detected by PCR and double stranded DNA sequencing. Escherichia coli phylogenetic groups were determined using a PCR-based method. RESULTS: ESBL-PE frequency was 58 % (179 strains among the 308 Enterobacteriaceae isolates identified in the collected samples; 45 % in outpatients and 70 % in hospitalized patients). The CTX-M-1 group was dominant (94 %, CTX-M-15 enzyme), followed by the CTX-M-9 group (4 %). ESBL producers were more often found in E. coli (67.5 %) and Klebsiella pneumoniae (26 %) isolates. E. coli isolates (n = 202; 60 % of all Enterobacteriaceae samples) were distributed in eight phylogenetic groups (A = 49, B1 = 15, B2 = 43, C = 22, Clade I = 7, D = 37, F = 13 and 16 unknown); 22 strains belonged to the sequence type ST131. No association between a specific strain and ESBL production was detected. CONCLUSIONS: This report shows the alarming spread of ESBL genes in Burkina Faso. Public health efforts should focus on education (population and healthcare professionals), surveillance and promotion of correct and restricted antibiotic use to limit their dissemination. PMID- 27400867 TI - Priming locus coeruleus noradrenergic modulation of medial perforant path-dentate gyrus synaptic plasticity. AB - Priming phenomenon, in which an earlier exposure to a stimulus or condition alters synaptic plasticity in response to a subsequent stimulus or condition, known as a challenge, is an example of metaplasticity. In this review, we make the case that the locus coeruleus noradrenergic system-medial perforant path dentate gyrus pathway is a neural ensemble amenable to studying priming-challenge effects on synaptic plasticity. Accumulating evidence points to a tyrosine hydroxylase-dependent priming effect achieved by pharmacological (nicotine and antipsychotics) or physiological (septal theta driving) manipulations of the locus coeruleus noradrenergic system that can facilitate noradrenaline-induced synaptic plasticity in the dentate gyrus of the hippocampus. The evidence suggests the hypothesis that behavioural experiences inducing tyrosine hydroxylase expression in the locus coeruleus may be sufficient to prime this form of metaplasticity. We propose exploring this phenomenon of priming and challenge physiologically, to determine whether behavioural experiences are sufficient to prime the locus coeruleus, enabling subsequent pharmacological or behavioural challenge conditions that increase locus coeruleus firing to release sufficient noradrenaline to induce long-lasting potentiation in the dentate gyrus. Such an approach may contribute to unravelling mechanisms underlying this form of metaplasticity and its importance in stress-related mnemonic processes. PMID- 27400868 TI - Unmet Needs for Clinical Ethics Support Services in Nurse: Based on focus group interviews. AB - BACKGROUND: As nurses' ethical competence in their own fields is essential, clinical ethics support services help nurses improve ethical competence. OBJECTIVES: The purpose of this study was to identify the unmet needs of ethical support for nurses in clinical settings and explore the differences by nursing units. RESEARCH DESIGN: Focus group interview design was applied. Participants and research context: Data were collected via four rounds of focus group interviews with 37 nurses at intensive care units, medical-surgical units, emergency departments and oncology units. Major questions were as follows: 'What is nurses' experience of ethical difficulties while working as a clinical nurse?' and 'What kinds of clinical ethics support services do nurses require in different clinical settings?' Inductive content analysis was performed to analyse the data. Ethical considerations: Ethical approval was obtained from the institutional review of board at the College of Nursing. FINDINGS: Five categories (with 14 subcategories) were identified: difficulty providing evidence based care, lack of support in maintaining patients' and family members' dignity, insufficient education regarding clinical ethics, loss of professional self esteem and expectations concerning organizational support. Nurses' desire for ethical support varied according to department. CONCLUSION: Nurses face both practical and existential ethical issues that require rapid solution each day. There is a need for ethical counselling to prevent compassion fatigue and identify means via which nurses reflect on their daily lives in their own fields. In-house training should be provided for each unit, to improve ethical competence and facilitate the development of pragmatic, sensible solutions. PMID- 27400869 TI - Free energy of solvation of carbon nanotubes in pyridinium-based ionic liquids. AB - Numerous prospective applications require the availability of individual carbon nanotubes (CNTs). Pristine CNTs, strongly hydrophobic in nature, are known to be either totally insoluble or poorly dispersible. While it is unlikely to be possible to prepare a real solution of CNTs in any solvent, the ability of certain solvents to maintain dispersions of CNTs for macroscopic times constitutes great research interest. In the present work, we characterize two pyridinium-based ionic liquids (ILs), N-butylpyridinium chloride [BPY][Cl] and N butylpyridinium bis(trifluoromethanesulfonyl)imide [BPY][TFSI], with respect to their potential to solvate CNTs of different diameters, from the CNT (10,10) to the CNT (25,25). Using a universal methodology, we found that both ILs exhibit essentially the same solvation performance. Solvation of CNTs is strongly prohibited entropically, whereas the energy penalty increases monotonically with the CNT diameter. Weak van der Waals interactions, which guide enthalpy alteration upon the CNT solvation, are unable to compensate for the large entropic penalty from the destruction of the IL-IL electrostatic interactions. The structure of ILs inside and outside CNTs is also discussed. The reported results are necessary for gaining a fundamental understanding of the CNT solvation problems, thereby inspiring the search for more suitable solvents. PMID- 27400870 TI - Alice in microbes' land: adaptations and counter-adaptations of vector-borne parasitic protozoa and their hosts. AB - In the present review, we aim to provide a general introduction to different facets of the arms race between pathogens and their hosts/environment, emphasizing its evolutionary aspects. We focus on vector-borne parasitic protozoa, which have to adapt to both invertebrate and vertebrate hosts. Using Leishmania, Trypanosoma and Plasmodium as main models, we review successively (i) the adaptations and counter-adaptations of parasites and their invertebrate host, (ii) the adaptations and counter-adaptations of parasites and their vertebrate host and (iii) the impact of human interventions (chemotherapy, vaccination, vector control and environmental changes) on these adaptations. We conclude by discussing the practical impact this knowledge can have on translational research and public health. PMID- 27400871 TI - Civil society advocacy in Nigeria: promoting democratic norms or donor demands? AB - BACKGROUND: Civil society organizations (CSOs) are often assumed to be institutions that facilitate communication between citizens and policymakers. However, CSO advocacy is only as effective as the space allowed by government, the resources available from funders, and their own internal capacity. This article presents findings from a study in Nigeria that explores the advocacy and service delivery roles of CSOs working in Human Immunodeficiency Virus (HIV) prevention and mitigation. We will argue that donor and government treatment of civil society as service delivery organizations, rather than as organizations that participate in democratic norms, have shaped how civil society organizations work to mitigate and prevent HIV. METHODS: From February to April 2012, a team of Health Systems 20/20 staff and one consultant conducted 48 in-depth interviews with civil society organizations, State AIDS Control Agencies (SACAs), donors, international organizations, and networks of people living with HIV to examine a wide range of advocacy efforts by CSOs. For quantitative data collection, sampling frames were assembled from lists of HIV-oriented or involved CSOs. This sampling frame consisted of 2548 CSOs from all 36 states and the Federal Capital Territory. A random sample was then taken from the sampling frame, and we contacted 665 CSOs to arrange interviews. With a response rate of 80.2 %, the project conducted 533 surveys in February 2012. RESULTS: These surveys showed that CSOs advocacy efforts focused on community mobilization related to behavior change, such as peer education (54.9 % of CSOs) and rallies (58.2 % of CSOs), and not on changing government policies. In-depth interviews highlighted the role of donors and government in shaping a purely apolitical role for most CSOs through funding constraints, regulations, and capacity development choices. CONCLUSIONS: In light of these findings, we present key points for considering the influence of donors and government on civil society advocacy for HIV services and rights. We present evidence that donors, and international organizations, conceive of civil society as apolitical, and not as independent actors that compete for political space. More democratic and rights-based views of civil society's role, such as holding government accountable for providing services or promoting policy change, are not emphasized. PMID- 27400872 TI - Effects of a case-based interactive e-learning course on knowledge and attitudes about patient safety: a quasi-experimental study with third-year medical students. AB - BACKGROUND: Patient safety (PS) is influenced by a set of factors on various levels of the healthcare system. Therefore, a systems-level approach and systems thinking is required to understand and improve PS. The use of e-learning may help to develop a systems thinking approach in medical students, as case studies featuring audiovisual media can be used to visualize systemic relationships in organizations. The goal of this quasi-experimental study was to determine if an e learning can be utilized to improve systems thinking, knowledge, and attitudes towards PS. METHODS: A quasi-experimental, longitudinal within- subjects design was employed. Participants were 321 third-year medical students who received online surveys before and after they participated in an e-learning course on PS. Primary outcome measures where levels of systems thinking and attitudes towards PS. Secondary outcome measures were the improvement of PS specific knowledge through the e-learning course. RESULTS: Levels of systems thinking showed significant improvement (58.72 vs. 61.27; p < .001) after the e-learning. Student's attitudes towards patient safety improved in several dimensions: After the course, students rated the influence of fatigue on safety higher (6.23 vs. 6.42, p < .01), considered patient empowerment more important (5.16 vs. 5.93, p < .001) and realized more often that human error is inevitable (5.75 vs. 5.97, p < .05). Knowledge on PS improved from 36.27 % correct answers before to 76.45 % after the e-learning (p < .001). CONCLUSIONS: Our results suggest that e-learning can be used to teach PS. Attitudes towards PS improved on several dimensions. Furthermore, we were able to demonstrate that a specifically designed e-learning program can foster the development of conceptual frameworks such as systems thinking, which facilitates the understanding of complex socio-technical systems within healthcare organisations. PMID- 27400873 TI - Cell therapies for pancreatic beta-cell replenishment. AB - The current treatment approach for type 1 diabetes is based on daily insulin injections, combined with blood glucose monitoring. However, administration of exogenous insulin fails to mimic the physiological activity of the islet, therefore diabetes often progresses with the development of serious complications such as kidney failure, retinopathy and vascular disease. Whole pancreas transplantation is associated with risks of major invasive surgery along with side effects of immunosuppressive therapy to avoid organ rejection. Replacement of pancreatic beta-cells would represent an ideal treatment that could overcome the above mentioned therapeutic hurdles. In this context, transplantation of islets of Langerhans is considered a less invasive procedure although long-term outcomes showed that only 10 % of the patients remained insulin independent five years after the transplant. Moreover, due to shortage of organs and the inability of islet to be expanded ex vivo, this therapy can be offered to a very limited number of patients. Over the past decade, cellular therapies have emerged as the new frontier of treatment of several diseases. Furthermore the advent of stem cells as renewable source of cell-substitutes to replenish the beta cell population, has blurred the hype on islet transplantation. Breakthrough cellular approaches aim to generate stem-cell-derived insulin producing cells, which could make diabetes cellular therapy available to millions. However, to date, stem cell therapy for diabetes is still in its early experimental stages. This review describes the most reliable sources of stem cells that have been developed to produce insulin and their most relevant experimental applications for the cure of diabetes. PMID- 27400874 TI - A qualitative study of online mental health information seeking behaviour by those with psychosis. AB - BACKGROUND: The Internet and mobile technology are changing the way people learn about and manage their illnesses. Little is known about online mental health information seeking behaviour by people with psychosis. This paper explores the nature, extent and consequences of online mental health information seeking behaviour by people with psychosis and investigates the acceptability of a mobile mental health application (app). METHODS: Semi-structured interviews were carried out with people with psychosis (n = 22). Participants were purposively recruited through secondary care settings in London. The main topics discussed were participants' current and historical use of online mental health information and technology. Interviews were audio-recorded, transcribed and analysed by a team of researchers using thematic analysis. RESULTS: Mental health related Internet use was widespread. Eighteen people described searching the Internet to help them make sense of their psychotic experiences, and to read more information about their diagnosis, their prescribed psychiatric medication and its side-effects. Whilst some participants sought 'expert' online information from mental health clinicians and research journals, others described actively seeking first person perspectives. Eight participants used this information collaboratively with clinicians and spoke of the empowerment and independence the Internet offered them. However nine participants did not discuss their use of online mental health information with their clinicians for a number of reasons, including fear of undermining their clinician's authority. For some of these people concerns over what they had read led them to discontinue their antipsychotic medication without discussion with their mental health team. CONCLUSIONS: People with psychosis use the Internet to acquire mental health related information. This can be a helpful source of supplementary information particularly for those who use it collaboratively with clinicians. When this information is not shared with their mental health team, it can affect patients' health care decisions. A partnership approach to online health-information seeking is needed, with mental health clinicians encouraging patients to discuss information they have found online as part of a shared decision-making process. Our research suggests that those with psychosis have active digital lives and that the introduction of a mental health app into services would potentially be well received. PMID- 27400876 TI - Family History and Probability of Prostate Cancer, Differentiated by Risk Category: A Nationwide Population-Based Study. AB - BACKGROUND: Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low- and high-risk prostate cancer. METHODS: Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non low- (any of Gleason score >= 7, prostate-specific antigen [PSA] >= 10 ng/mL, T3 4, N1, and/or M1) and high-risk prostate cancer (Gleason score >= 8 and/or T3-4 and/or PSA >= 20 ng/mL and/or N1 and/or M1). RESULTS: The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age 75 years, and of high-risk prostate cancer 1.4% (95% CI = 1.3% to 1.4%) at age 65 years and 5.2% (95% CI = 5.1% to 5.2%) at age 75 years. For men with one affected brother, probabilities of any prostate cancer were 14.9% (95% CI = 14.1% to 15.8%) at age 65 years and 30.3% (95% CI = 29.3% to 31.3%) at age 75 years, of non-low-risk prostate cancer 7.3% (95% CI = 6.7% to 7.9%) at age 65 years and 18.8% (95% CI = 17.9% to 19.6%) at age 75 years, and of high-risk prostate cancer 3.0% (95% CI = 2.6% to 3.4%) at age 65 years and 8.9% (95% CI = 8.2% to 9.5%) at age 75 years. Probabilities were higher for men with a stronger family history. For example, men with two affected brothers had a 13.6% (95% CI = 9.9% to 17.6 %) probability of high-risk cancer at age 75 years. CONCLUSIONS: The age-specific probabilities of non-low- and high-risk cancer presented here are more informative than relative risks of any prostate cancer and more suitable to use for counseling men with a family history of prostate cancer. PMID- 27400875 TI - Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia. AB - BACKGROUND: Microglia are resident myeloid cells in the CNS that are activated by infection, neuronal injury, and inflammation. Established BV2 microglial cell lines have been the primary in vitro models used to study neuroinflammation for more than a decade because they reduce the requirement of continuously maintaining cell preparations and animal experimentation models. However, doubt has recently been raised regarding the value of BV2 cell lines as a model system. METHODS: We used triplicate RNA sequencing (RNA-seq) to investigate the molecular signature of primary and BV2 microglial cell lines using two transcriptomic techniques: global transcriptomic biological triplicate RNA-seq and quantitative real-time PCR. We analyzed differentially expressed genes (DEGs) to identify transcription factor (TF) motifs (-950 to +50 bp of the 5' upstream promoters) and epigenetic mechanisms. RESULTS: Sequencing assessment and quality evaluation revealed that primary microglia have a distinct transcriptomic signature and express a unique cluster of transcripts in response to lipopolysaccharide. This microglial signature was not observed in BV2 microglial cell lines. Importantly, we observed that previously unidentified TFs (i.e., IRF2, IRF5, IRF8, STAT1, STAT2, and STAT5A) and the epigenetic regulators KDM1A, NSD3, and SETDB2 were significantly and selectively expressed in primary microglia (PM). Although transcriptomic alterations known to occur in BV2 microglial cell lines were identified in PM, we also observed several novel transcriptomic alterations in PM that are not frequently observed in BV2 microglial cell lines. CONCLUSIONS: Collectively, these unprecedented findings demonstrate that established BV2 microglial cell lines are probably a poor representation of PM, and we establish a resource for future studies of neuroinflammation. PMID- 27400877 TI - Global structure search and physical properties of Os2C. AB - The crystal structures of Os2C were extensively investigated using the structure search method from the first-principles calculations. In contrast to the P6 3 /mmc phase previously proposed as the ground state at ambient pressure, an energetically favorable structure with space group P-6m2 was found more stable at ambient condition. The structural stabilities of the new phase are confirmed by the phonon dispersion and elastic constants. Further calculations indicate that the newly predicted P-6m2 phase is ultra-incompressible with a high bulk modulus of 387 GPa and has a larger ideal shear strength than the P6 3 /mmc phase. PMID- 27400879 TI - ACEM trainee opportunities in subspecialist domains: Experience from ultrasound, pre-hospital and medical education terms. PMID- 27400878 TI - Antimicrobial and anti-Quorum Sensing activities of selected medicinal plants of Ethiopia: Implication for development of potent antimicrobial agents. AB - BACKGROUND: Traditional medicinal plants have been used as an alternative medicine in many parts of the world, including Ethiopia. There are many documented scientific reports on antimicrobial activities of the same. To our knowledge, however, there is no report on the anti-Quorum Sensing (Quorum Quenching, QQ) potential of traditional Ethiopian medicinal plants. As many of the opportunistic pathogenic bacteria depend on Quorum Sensing (QS) systems to coordinate their virulence expression, interference with QS could be a novel approach to control bacterial infections. Thus, the aim of this study was to evaluate selected medicinal plants from Ethiopia for their antimicrobial activities against bacterial and fungal pathogens; and to assess the interference of these plant extracts with QS of bacteria. METHODS: Antimicrobial activities of plant extracts (oil, resins and crude extracts) were evaluated following standard agar diffusion technique. The minimum inhibitory concentrations (MIC) of potent extracts were determined using 96 well micro-titer plates and optical densities were measured using an ELISA Microplate reader. Interference with Quorum Sensing activities of extracts was determined using the recently established E. coli based reporter strain AI1-QQ.1 and signaling molecule N-(beta-ketocaproyl)-L homoserine lactone (3-oxo-C6-HSL). RESULTS: Petroleum ether extract of seed of Nigella sativa exhibited the highest activity against both the laboratory isolated Bacillus cereus [inhibition zone (IZ), 44 +/- 0.31 mm] and B. cereus ATCC 10987 (IZ, 40 +/- 2.33 mm). Similarly, oil extract from mature ripe fruit husk of Aframomum corrorima and mature unripe fruit of A. corrorima revealed promising activities against Candida albicans ATCC 90028 (IZ, 35 +/- 1.52 mm) and Staphylococcus aureus DSM 346 (IZ, 25 +/- 1.32 mm), respectively. Antimicrobial activities of oil extract from husk of A. corrorima and petroleum ether extract of seed of N. sativa were significantly higher than that of the control antibiotic [Gentamycin sulfate, (IZ, 25-30 mm)]. The lowest MIC value (12.5 mg/mL) was recorded for oil from husk of A. corrorima against Pseudomonas aeruginosa. Of the total eighteen extracts evaluated, two of the extracts [Methanol extract of root of Albiza schimperiana (ASRM) and petroleum ether extract of seed of Justica schimperiana (JSSP)] interfered with cell-cell communication most likely by interacting with the signaling molecules. CONCLUSION: Traditional medicinal plants from Ethiopia are potential source of alternative medicine for the local community and scientific research in search for alternative drugs to halt challenges associated with the emerging antimicrobial resistance. Furthermore, the Quorum Quenching activities observed in two of the plant extracts calls for more comprehensive evaluation of medicinal plants for the control of many bacterial processes and phenotypic behaviors such as pathogenicity, swarming, and biofilm formation. Being the first assessment of its kind on the potential application of Ethiopian traditional medicinal plants for interference in microbial cell-cell communication (anti-Quorum Sensing activities), the detailed chemistry of the active compounds and possible mechanism(s) of actions of the bio-molecules responsible for the observed interference were not addressed in the current study. Thus, further evaluation for the nature of those active compounds (bio-molecules) and detailed mechanism(s) of their interaction with microbial processes are recommended. PMID- 27400880 TI - A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma. AB - BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant syndrome caused by activating germline mutations in the RET (REarranged during Transfection) proto-oncogene. MEN 2A has a strong (>95%) and age-dependent (5-25 years) clinical penetrance of medullary thyroid carcinoma (MTC). Several major studies have analyzed the predictive and prognostic factors for MEN 2A to find indicators that predict the optimal timing of prophylactic thyroidectomy. The aims of this study were to describe all known RET positive MEN 2A patients diagnosed in Norway and to evaluate the clinical course of MTC, as well as its predictive and prognostic factors. METHODS: This nationwide retrospective cohort study included data for 65 (14 index and 51 screening patients) out of a total of 67 MEN 2A patients with the RET gene mutation who were diagnosed in Norway since 1974. Data were collected by reviewing patient files. The variables analyzed were genotype, phenotype, preoperative basal calcitonin, age at thyroid surgery, central lymph node dissection and nodal status at primary surgery, number of surgical procedures, and biochemical cure. Of the 65 patients, 60 had undergone thyroid surgery. The median follow-up period was 9.9 years. The patients were divided into pre-RET-and RET-era, which included patients who had thyroid surgery before January 1, 1994, and after, respectively. RESULTS: In index and screening patients, MTC was found, respectively, in 100% and 45% of cases, central lymph node dissection at primary surgery was done for 64% and 52% of patients, and the median total number of surgical procedures was two (range 1-6) and one (range 1 4). At primary surgery, all patients (n = 13) with lymph node metastases had preoperative basal calcitonin levels >=68 pg/mL, and all patients (n = 17) without central lymph node dissection and preoperative basal calcitonin <40 pg/mL were biochemically cured. Multivariate analysis showed that preoperative basal calcitonin was a significant predictive factor for MTC superior to age at thyroid surgery when analyzing the entire period (p = 0.009) and the RET-era separately (p = 0.021). Prognostic factors for biochemical cure were preoperative basal calcitonin, central lymph node dissection, and nodal status at primary surgery (p = 0.037, p = 0.002, and p = 0.005) when analyzing the entire period, but only nodal status at primary surgery when the RET-era was considered separately (p = 0.006). CONCLUSIONS: Preoperative basal calcitonin alone can serve as an indicator for optimal timing and the extent of thyroid surgery for MEN 2A patients that could be considered safe. The results are consistent with previously reported data. PMID- 27400881 TI - Waist circumference is superior to weight and BMI in predicting sexual symptoms, voiding symptoms and psychosomatic symptoms in men with hypogonadism and erectile dysfunction. AB - Waist circumference is considered a useful predictor of obesity-associated cardiovascular risk, but its use as an indicator of sexual health status and quality of life (QoL) in hypogonadal men is unknown. We investigated whether three measurements of obesity, weight, body mass index and waist circumference, correlate with the International Index of Erectile Function-5 (IIEF-5), the Aging Males' Symptoms (AMS) and the International Prostate Symptom Score (IPSS) questionnaires. A total of 261 patients were enrolled in a prospective study on hypogonadism treatment with intramuscular long-acting testosterone undecanoate. Patients with total testosterone <=3.5 ng ml-1 were enrolled, and baseline demographic data were recorded. Patient's response to IIEF, IPSS and AMS standardised questionnaires was recorded to evaluate health-related QoL. The mean length of treatment and follow-up was 4.7 years (max 6 years). ANOVA regression analysis showed that waist circumference was significantly inversely proportional to IIEF-5 and directly proportional to AMS and IPSS. Weight was inversely proportional to IIEF and directly proportional to IPSS but not associated with AMS. BMI had no proportionality to measurements of sexual function and quality of life. These results suggest that among weight, BMI and waist circumference, the latter is the best predictor of health-related QoL in men with hypogonadism. PMID- 27400882 TI - Duloxetine in elderly major depression disorder: effectiveness and drug plasma level evaluation. AB - OBJECTIVE: The aim of this open-label naturalistic study was to assess clinical outcomes and the predictive value of duloxetine plasma levels in major depressive disorder in the elderly. METHODS: This naturalistic, open-label design involved 35 outpatients aged between 65 and 87 years. Duloxetine plasma levels were collected in 24 patients after the first month. Patients were evaluated using 21 item Hamilton Rating Scales for Depression, Hamilton Rating Scales for Anxiety, the Clinical Global Impression Severity, Mini Mental State Examination, Cumulative Illness Rating Scale, Barthel Index and Beck's Depression Inventory. RESULTS: Duloxetine plasma levels at T2 ranged from 4.9 to 201.9 ng/mL without a significant correlation between duloxetine dose and plasma levels. A significant improvement in mean 21-item Hamilton Rating Scales for Depression total scores at T2,T3, T4, T9 and T12 and a progressive significantly decrease of the mean Hamilton Rating Scales for Anxiety scores from T3 to T12 were observed. CONCLUSIONS: The levels of duloxetine in plasma do not correlate with a greater clinical improvement, indeed appear to adversely affect the improvement of the Beck Depression Inventory and Hamilton Rating Scales for Anxiety. This could be explained by an increase in side effects that may aggravate the discomfort felt by the patient. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27400884 TI - Case of bullous pemphigoid in a 28-year-old woman affected by tuberous sclerosis complex. PMID- 27400883 TI - The triptolide derivative MRx102 inhibits Wnt pathway activation and has potent anti-tumor effects in lung cancer. AB - BACKGROUND: The natural compound triptolide has been shown to decrease cell proliferation and induce apoptosis and cellular senescence. We previously demonstrated that triptolide decreases tumor formation and metastasis of human non-small cell lung cancer cells (NSCLC). Due to the toxicity of triptolide, derivatives of the natural compound have been developed that show more favorable toxicity profiles and pharmacokinetics in animal models. The purpose of this study was to evaluate MRx102 as a novel therapeutic for lung cancer. METHODS: Mice injected subcutaneously with H460 lung cancer cells were treated with MRx102 or carboplatin to determine the effect of MRx102 on tumor formation in comparison to standard treatment. Patient-derived xenografts (PDX) with different WIF1 expression levels were treated with MRx102 or cisplatin. We tested the effects of MRx102 treatment on migration and invasion of lung cancer cells using Transwell filters coated with fibronectin and Matrigel, respectively. Tail vein injections using H460 and A549 cells were performed. RESULTS: Here we report that the triptolide derivative MRx102 significantly decreases NSCLC proliferation and stimulates apoptosis. Further, MRx102 potently inhibits NSCLC haptotactic migration and invasion through Matrigel. In vivo, NSCLC tumor formation and metastasis were greatly decreased by MRx102 treatment. The decrease in tumor formation by MRx102 in the patient-derived xenograft model was WIF1-dependent, demonstrating that MRx102 is a potent inhibitor of the Wnt pathway in low WIF1 expressing NSCLC patient tumors. CONCLUSIONS: These results indicate that MRx102 has potent antitumor effects both in vitro and in vivo, and is a potential novel therapy for the treatment of NSCLC. PMID- 27400885 TI - Epidermal barrier function changes after ablative and non-ablative fractional laser administration. PMID- 27400886 TI - Synthesis of functionalized amino epoxides by a three-component coupling involving aziridines, arynes and aldehydes. AB - A transition-metal-free three-component coupling involving N-substituted aziridines, arynes and aldehydes resulting in the formation of trisubstituted N aryl alpha-amino epoxides has been demonstrated. The reaction likely proceeds via the highly strained cyclic nitrogen ylide intermediates generated from aziridines and arynes. PMID- 27400887 TI - Cytotoxic prenylated flavones from the stem and root bark of Daphne giraldii. AB - Three new prenylated flavones (1-3), along with three known analogues (4-6), were isolated from the stem and root bark of Daphne giraldii. Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. The absolute configurations of compounds 2 and 3 were assigned by optical rotation comparison, CD and [Rh2(OCOCF3)4]-induced CD spectral methods. The in vitro cytotoxicity experiments carried out involving five cancer cell lines (U251, A549, HepG2, MCF-7 and Bcap37) showed that 2 markedly inhibited the proliferation of all tested cells with IC50 values ranging from 4.26 to 20.82MUM. The preliminary structure-activity relationships of these flavones are discussed. In addition, compound 2 was found to effectively induce apoptosis in HepG2 cells according to a flow cytometry analysis. PMID- 27400888 TI - Antioxidant properties of thio-caffeine derivatives: Identification of the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine as antioxidant and highly potent cytoprotective agent. AB - A series of nine thio-caffeine analogues were synthesized and characterised by NMR, FT-IR and MS spectroscopic methods. Molecular structures of four of them were determined using single crystal X-ray diffraction methods. The antioxidant properties of all compounds, at concentration ranges from 0.025 to 0.1mg/mL, were evaluated by various chemical- and cell-based antioxidant assays. Human erythrocytes were used to examine in vitro haemolytic activity of all compounds and their protective effect against oxidative haemolysis induced by AAPH, one of the commonly used free radical generator. All compounds studied showed no effect on the human erythrocytes membrane structure and permeability with the exception of 8-(phenylsulfanyl)caffeine. Among the nine caffeine thio-analogues tested, the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine possessed exceptionally high antioxidant properties. Moreover, it protects human erythrocytes against AAPH-induced oxidative damage as efficiently as the standard antioxidant Trolox. Therefore, 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine may have a significant cytoprotective potential caused by its antioxidant activity. PMID- 27400889 TI - Synthesis, biological evaluation and molecular docking of 2-phenyl benzo[d]oxazole-7-carboxamide derivatives as potential Staphylococcus aureus Sortase A inhibitors. AB - A series of novel 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives were designed, synthesized and evaluated for their in vitro inhibitory activities against Staphylococcus aureus Sortase A with known Sortase A inhibitor pHMB as positive compound (IC50=130MUM). Most compounds exhibited excellent inhibitory activity (IC50=19.8-184.2MUM). Structure-activity relationship studies demonstrated that substitution at 7-position and 2-position of benzoxazole had great influence on the activities. Specifically, the substituent at 7-position is indispensable for inhibitory activity. The molecular docking studies revealed the i-butyl amide group went towards the beta6/beta7 loop-beta8 substructure of the protein and the benzoxazole core lied in a hydrophobic pocket composed of Ala118, Val166, Val168, Val169 and Ile182, shaping the whole molecule into a L-shape mode to be recognized by Sortase A. PMID- 27400890 TI - Adaptive paediatric investigation plans, a small step to improve regulatory decision making in drug development for children? AB - Different arguments have been put forward why drug developers should commit themselves early for what they are planning to do for children. By EU regulation, paediatric investigation plans should be agreed on in early phases of drug development in adults. Here, extrapolation from adults to children is widely applied to reduce the burden and avoids unnecessary clinical trials in children, but early regulatory decisions on how far extrapolation can be used may be highly uncertain. Under special circumstances, the regulatory process should allow for adaptive paediatric investigation plans explicitly foreseeing a re-evaluation of the early decision based on the information accumulated later from adults or elsewhere. A small step towards adaptivity and learning from experience may improve the quality of regulatory decisions in particular with regard to how much information can be borrowed from adults. (c) 2016 The Authors. Pharmaceutical Statistics Published by John Wiley & Sons Ltd. PMID- 27400891 TI - Effectiveness and safety of continuous ultrasound-guided femoral nerve block versus epidural analgesia after total knee arthroplasty. AB - OBJECTIVES: Total knee arthroplasty is associated with severe postoperative pain. The aim of this study was to compare continuous ultrasound-guided femoral nerve block with continuous epidural analgesia, both with low concentrations of local anaesthetic after total knee arthroplasty. MATERIAL AND METHODS: A prospective, randomised, unblinded study of 60 patients undergoing total knee replacement, randomised into two groups. A total of 30 patients received continuous epidural block, while the other 30 received continuous ultrasound-guided femoral nerve block, as well as using 0.125% levobupivacaine infusion in both groups. Differences in pain control, undesirable effects, and complications between the two techniques were assessed, as well as the need for opioid rescue and the level of satisfaction with the treatment received during the first 48hours after surgery. RESULTS: No differences were found in demographic and surgical variables. The quality of analgesia was similar in both groups, although in the first six hours after surgery, patients in the epidural group had less pain both at rest and with movement (P=.007 and P=.011). This difference was not observed at 24hours (P=.084 and P=.942). Pain control at rest in the femoral block group was better at 48hours after surgery than in the epidural group (P=.009). The mean consumption of morphine and level of satisfaction were similar. Epidural analgesia showed the highest rate of side effects (P=.003). CONCLUSIONS: Continuous ultrasound-guided femoral nerve block provides analgesia and morphine consumption similar to epidural analgesia, with the same level of satisfaction, but with a lower rate of side effects after total knee arthroplasty. PMID- 27400892 TI - Insight into the formation of the tert-butyl cation confined inside H-ZSM-5 zeolite from NMR spectroscopy and DFT calculations. AB - Solid-state NMR experiments and DFT calculations have been carried out to determine the complex structures of coadsorbed (13)C-labeled tert-butanol and NH3 in acidic H-ZSM-5 zeolite. It is found, besides the physically adsorbed tert butanol/NH4(+) complex on Bronsted acid sites, the tert-butylamine cation is formed as well, confirming the presence of the tert-butyl cation confined in zeolite channels. Furthermore, (13)C-(27)Al double-resonance solid-state NMR spectroscopy is adopted to determine the host/guest interaction between the carbocation and the zeolite framework. PMID- 27400893 TI - Is Statin Monotherapy the Perfect Polypill? PMID- 27400894 TI - Is the Mortality Benefit With Empagliflozin in Type 2 Diabetes Mellitus Too Good To Be True? PMID- 27400895 TI - The Birth, and Evolution, of Percutaneous Coronary Interventions: A Conversation With Patrick Serruys, MD, PhD. PMID- 27400897 TI - Seeking a Cure for One of the Rarest Diseases: Progeria. PMID- 27400896 TI - Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. AB - BACKGROUND: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. METHODS: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. RESULTS: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. CONCLUSIONS: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747. PMID- 27400899 TI - Bioresorbable Vascular Scaffolds for Coronary Revascularization. AB - Contemporary metallic drug-eluting stents are associated with very good 1-year outcomes but an ongoing risk of stent-related adverse events (thrombosis, myocardial infarction, restenosis) after 1 year. The pathogenesis of these very late events is likely related to the permanent presence of the metal stent frame or polymer. Bioresorbable scaffolds have been developed to provide drug delivery and mechanical support functions similar to metallic drug-eluting stents, followed by complete resorption with recovery of more normal vascular structure and function, potentially improving very late clinical outcomes. A first generation bioresorbable scaffold has been demonstrated to be noninferior to a contemporary metallic drug-eluting stents for overall 1-year patient-oriented and device-oriented outcomes. Increased rates of scaffold thrombosis and target vessel-related myocardial infarction were noted that may be mitigated by improved patient and lesion selection, procedural technique, and device iteration. Large scale, randomized, clinical trials are ongoing to determine the long-term relative efficacy and safety of bioresorbable scaffolds compared with current metallic drug-eluting stents. PMID- 27400898 TI - One-Year Clinical Outcomes With SAPIEN 3 Transcatheter Aortic Valve Replacement in High-Risk and Inoperable Patients With Severe Aortic Stenosis. AB - BACKGROUND: In the initial PARTNER trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement for high-risk (HR) and inoperable patients, mortality at 1 year was 24% in HR and 31% in inoperable patients. A recent report of the 30-day outcomes with the low-profile SAPIEN 3 transcatheter aortic valve replacement system demonstrated very low rates of adverse events, but little is known about the longer-term outcomes with this device. METHODS: Between October 2013 and September 2014, 583 HR (65%) or inoperable (35%) patients were treated via the transfemoral (84%) or transapical/transaortic (16%) access route at 29 US sites. Major clinical events at 1 year were adjudicated by an independent clinical events committee, and echocardiographic results were analyzed by a core laboratory. RESULTS: Baseline characteristics included age of 83 years, 42% female, and median Society of Thoracic Surgeons score of 8.4%. At the 1-year follow-up, survival (all-cause) was 85.6% for all patients, 87.3% in the HR subgroup, and 82.3% in the inoperable subgroup. Survival free of all-cause and cardiovascular mortality in the transfemoral patients from the HR cohort was 87.7% and 93.3%, respectively. There was no severe paravalvular leak. Moderate paravalvular leak (2.7%) was associated with an increase in mortality at 1 year, whereas mild paravalvular leak had no significant association with mortality. Symptomatic improvement as assessed by the percentage of patients in New York Heart Association class III and IV (90.1% to 7.7% at 1 year; P<0.0001) and by Kansas City Cardiomyopathy Questionnaire overall summary score (improved from 46.9 to 72.4; P<0.0001) was marked. Multivariable predictors of 1-year mortality included alternative access, Society of Thoracic Surgeons score, and disabling stroke. CONCLUSIONS: In this large, adjudicated registry of SAPIEN 3 HR and inoperable patients, the very low rates of important complications resulted in a strikingly low mortality rate at 1 year. Between 30 and 365 days, the incidence of moderate paravalvular aortic regurgitation did not increase, and no association between mild paravalvular leak and 1-year mortality was observed, although a small increase in disabling stroke occurred. These results, which likely reflect device iteration and procedural evolution, support the use of transcatheter aortic valve replacement as the preferred therapy in HR and inoperable patients with aortic stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313. PMID- 27400900 TI - Letter by Bouatou et al Regarding Article, "Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation". PMID- 27400901 TI - Letter by Imprialos et al Regarding Article, "Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation". PMID- 27400902 TI - Response by Piccini et al to Letters Regarding Article, "Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation". PMID- 27400903 TI - Erroneous inflation of diabetes prevalence: Are there global implications? AB - Comparison of the prevalence of type 2 diabetes mellitus (T2DM) in adults aged 25 64 years in selected Pacific Island countries using whole blood and plasma glucose cut-off points. Unit records of STEPwise approach to Surveillance (STEPS) surveys obtained from Fiji, Samoa, and Tonga Ministries of Health; T2DM prevalence recalculated using whole blood and plasma cut-off points. Shaded bars indicate T2DM prevalence based on correct glucose cut-off points for the glucose meter used (fasting blood glucose [FBG] >=6.1 mmol/L for early surveys1,3,5 ; fasting plasma glucose [FPG] >=7.0 mmol/L for later surveys),2,4,6 whereas open bars show T2DM prevalence based on incorrect glucose cut-off points (FPG >=6.1 mmol/L for later surveys).2,4,6 Highlights Incorrect glucose cut-off points were applied to the Fiji 2011, Samoa 2013, and Tonga 2012 STEPS surveys. This doubled the actual T2DM prevalences compared to using the correct glucose cut-off points. The errors occurred due to modern glucose meters producing measurements in plasma equivalent concentrations from whole blood samples. The incorrect whole blood glucose cut-off (>=6.1mmol/L) was applied instead of the correct plasma glucose cut-off (>=7.0mmol/L). This error likely affects other Pacific states, and may have global ramifications. PMID- 27400904 TI - Health risk assessment for exposure to nitrate in drinking water from village wells in Semarang, Indonesia. AB - The levels of nitrate in 52 drinking water wells in rural Central Java, Indonesia were evaluated in April 2014, and the results were used for a health risk assessment for the local populations by using probabilistic techniques. The concentrations of nitrate in drinking water had a range of 0.01-84 mg/L, a mean of 20 mg/L and a medium of 14 mg/L. Only two of the 52 samples exceeded the WHO guideline values of 50 mg/L for infant methaemoglobinaemia. The hazard quotient values as evaluated against the WHO guideline value at the 50 and 95 percentile points were HQ50 at 0.42 and HQ95 at 1.2, respectively. These indicated a low risk of infant methaemoglobinaemia for the whole population, but some risk for the sensitive portion of the population. The HQ50 and HQ95 values based on WHO acceptable daily intake dose for adult male and female were 0.35 and 1.0, respectively, indicating a generally a low level of risk. A risk characterisation linking birth defects to nitrate levels in water consumed during the first three months of pregnancy resulted in a HQ50/50 values of 1.5 and a HQ95/5 value of 65. These HQ values indicated an elevated risk for birth defects, in particular for the more sensitive population. A sanitation improvement program in the study area had a positive effect in reducing nitrate levels in wells and the corresponding risk for public health. For example, the birth defect HQ50/50 values for a subset of wells surveyed in both 2014 and 2015 was reduced from 1.1 to 0.71. PMID- 27400905 TI - Persistent organic pollutants in the Antarctic coastal environment and their bioaccumulation in penguins. AB - Persistent organic pollutants (POPs), including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), polybrominated biphenyls (PBBs), and polybrominated diphenyl ethers (PBDEs), have been identified in penguins, lichens, soils, and ornithogenic soils in the Antarctic coastal environment in this study. To the best of our knowledge, no previous study has reported PBDD/F and PBB data from Antarctica. The POP mass contents in penguins were in the following order: PCBs >> PBDEs >> PCDD/Fs; PCBs were the dominant pollutants (6310-144,000 pg/g-lipid), with World Health Organization toxic equivalency values being 2-14 times higher than those of PCDD/Fs. Long-range atmospheric transport is the most primary route by which POPs travel to Antarctica; however, local sources, such as research activities and penguin colonies, also influence POP distribution in the local Antarctic environment. In penguins, the biomagnification factor (BMF) of PCBs was 61.3-3760, considerably higher than that for other POPs. According to BMF data in Adelie penguins, hydrophobic PBDE congeners were more biomagnified at log Kow > 6, and levels decreased at log Kow > 7.5 because larger molecular sizes inhibited transfer across cell membranes. PMID- 27400906 TI - Exposure and size distribution of nitrated and oxygenated polycyclic aromatic hydrocarbons among the population using different household fuels. AB - Polycyclic aromatic hydrocarbons (PAHs) derivatives like nitrated and oxygenated PAHs are of growing concerns because of considerably higher toxicity and important roles during atmospheric chemical reactions. Residential solid fuel combustion is likely to be one large primary source of these pollutants in developing countries. In this study, inhalation exposure to nitrated and oxygenated PAH derivatives was evaluated among rural residents using carried samplers. The exposure levels of individual nitrated PAHs ranged from 4.04 (9 nitrated phenanthrene) to 89.8 (9-nitrated anthracene) pg/m(3), and of oxy-PAHs were 0.570 (benzo[a]anthracene-7, 12-dione) to 7.99 (Benzanthrone) ng/m(3), generally higher in wood user than that in anthracite user. A majority of derivatives in particle presented in PM2.5 (80% for nitrated naphthalene and over 90% for other targets) and even fine PM1.0. Mass fractions of PAH derivatives in fine and ultra-fine particles were significantly higher than the fractions of corresponding parent PAHs, indicating more adverse health outcomes induced by these derivatives. The inhalation exposure levels for residents adopting wood gasifier burners was significantly lower than the documented results for those burning wood in typical built-in brick stoves, and comparable to those using LPG and electricity, which provided vital information for clean stove development and intervention programs. PMID- 27400907 TI - The Inaccuracy of Patient Recall for COPD Exacerbation Rate Estimation and Its Implications: Results from Central Adjudication. AB - BACKGROUND: COPD exacerbation incidence rates are often ascertained retrospectively through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single-physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification. METHODS: Self-reported exacerbations (event-based definition) in 409 primary care patients with COPD participating in the International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) cohort were ascertained every 6 months over 3 years. Exacerbations were adjudicated by single experienced physicians and an adjudication committee who had information from patient charts. We assessed the accuracy (sensitivities and specificities) of self-reports and single-physician chart review against a central adjudication committee (AC) (reference standard). We used multinomial logistic regression and bootstrap stability analyses to explore determinants of misclassifications. RESULTS: The AC identified 648 exacerbations, corresponding to an incidence rate of 0.60 +/- 0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate, 0.75 +/- 1.01; incidence proportion, 59.7%). The sensitivity and specificity of self-reports were 84% and 76%, respectively, those of single-physician chart review were between 89% and 96% and 87% and 99%, respectively. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with underreporting and overreporting of exacerbations (underreporters: relative risk ratio [RRR], 2.16; 95% CI, 1.76 2.65 and overreporters: RRR, 1.67; 95% CI, 1.39-2.00). CONCLUSIONS: Patient 6 month recall of exacerbation events are inaccurate. This may lead to inaccurate estimates of incidence measures and underestimation of treatment effects. The use of multiple data sources combined with event adjudication could substantially reduce sample size requirements and possibly cost of studies. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT00706602. PMID- 27400908 TI - Protracted Bacterial Bronchitis in Children: Natural History and Risk Factors for Bronchiectasis. AB - BACKGROUND: Protracted bacterial bronchitis (PBB) and bronchiectasis are distinct diagnostic entities that share common clinical and laboratory features. It is postulated, but remains unproved, that PBB precedes a diagnosis of bronchiectasis in a subgroup of children. In a cohort of children with PBB, our objectives were to (1) determine the medium-term risk of bronchiectasis and (2) identify risk factors for bronchiectasis and recurrent episodes of PBB. METHODS: One hundred sixty-one children with PBB and 25 control subjects were prospectively recruited to this cohort study. A subset of 106 children was followed for 2 years. Flexible bronchoscopy, BAL, and basic immune function tests were performed. Chest CT was undertaken if clinical features were suggestive of bronchiectasis. RESULTS: Of 161 children with PBB (66% boys), 13 were diagnosed with bronchiectasis over the study period (8.1%). Almost one-half with PBB (43.5%) had recurrent episodes (> 3/y). Major risk factors for bronchiectasis included lower airway infection with Haemophilus influenzae (recovered in BAL fluid) (P = .013) and recurrent episodes of PBB (P = .003). H influenzae infection conferred a more than seven times higher risk of bronchiectasis (hazard ratio, 7.55; 95% CI, 1.66-34.28; P = .009) compared with no H influenzae infection. The majority of isolates (82%) were nontypeable H influenzae. No risk factors for recurrent PBB were identified. CONCLUSIONS: PBB is associated with a future diagnosis of bronchiectasis in a subgroup of children. Lower airway infection with H influenzae and recurrent PBB are significant predictors. Clinicians should be cognizant of the relationship between PBB and bronchiectasis, and appropriate follow-up measures should be taken in those with risk factors. PMID- 27400910 TI - Effect of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), on female breast cancer survivors in mainland China-A randomized, controlled, theoretically-derived intervention trial. AB - To reduce the risk of adjustment problems for breast cancer patients in mainland China, we examined the efficacy of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), delivered after breast surgery to (a) increase protective factors of social support, hope for the future, etc.; (b) decrease risk factors of Physical and Emotional Distress; and (c) increase outcomes of Resilience, Transcendence and Quality of Life (QOL). A multisite randomized controlled trial was conducted at 6 specialist cancer hospitals. 101 and 103 breast cancer patients were allocated to intervention group (IG) and control group (CG), respectively, and 112 general females (without breast cancer) were allocated to the norm group (NG). Participants completed measures that were related to latent variables derived from the Resilience Model for Breast Cancer (RM-BC) at baseline (T1), 2 months (T2), 6 months (T3), and 12 months (T4) after intervention. At T2, the IG reported significantly lower Depression (ES = 0.65,P = 0.0019) and Illness Uncertainty (ES = 0.57, P = 0.004), better Hope (ES = 0.81, P < 0.001) and QOL (ES = 0.60, P = 0.002) than did the CG. At T3, the IG reported significantly lower Anxiety (ES = 0.74, P < 0.001), better Social Support (ES = 0.51,P = 0.009), Transcendence (ES = 0.87, P < 0.001), and Resilience (ES = 0.83, P < 0.001) compared with the CG. At T4, the IG reported better Resilience though not significant (P = 0.085) and better Transcendence (P = 0.0243) than did the NG. The BRBC intervention improves the positive health outcomes and decreases the risk factors of illness-related distress of breast cancer patients during the high-risk cancer treatment. PMID- 27400911 TI - Mastectomy versus breast conservation treatment: is there a true survival difference? PMID- 27400909 TI - Treatment of ARDS With Prone Positioning. AB - Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS. PMID- 27400913 TI - Disparities in Access to Outpatient Rehabilitation Therapy for African Americans with Arthritis. AB - BACKGROUND: Approximately, 10 million Americans have an outpatient physical therapy or occupational therapy visit per year. This population is largely Caucasian, insured, educated and middle or high income. PURPOSE: The purpose of this study was to determine the existence of racial and/or ethnic disparities in patients with self-reported arthritis accessing office-based therapy services in the USA. METHOD: A pooled analytic file of 2008-2010 data from the Medical Expenditure Panel Survey-Household Survey was created. We first conducted a descriptive analysis of the utilization of therapy services for persons reporting arthritis. From the descriptive analysis, we formulated experimental hypotheses that we tested to determine if a racial disparity existed to access therapy services between White and Asian persons with arthritis and Black/Hispanic populations. To test our hypotheses, we determined the odd ratios using a logistic regression analysis. We conducted a similar analysis controlling for education, income, and insurance status. RESULTS: Eight percent of the US adult population with self-reported arthritis has an office-based therapy visit each year. Hispanic and Black Americans with arthritis have a reduced odds of a therapy visit (26.5 % [95 % CI 7-42 %] and 44.8 % [95 % CI 31.9-55.3 %], respectively). We did not find a similar effect on odds of a therapy visit for the Asian American population. The effect of race/ethnicity on the odds of a therapy visit was moderated by socioeconomic variables but persists for Black Americans. DISCUSSION/CONCLUSION: The results of this study confirm a reduced likelihood of an office-based therapy visit for Black Americans with arthritis when controlled for income, insurance, and education. An effect of race/ethnicity on the likelihood of a therapy visit for Hispanic Americans with arthritis disappears when controlled for income, insurance, and education. PMID- 27400912 TI - Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials. AB - A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen. PMID- 27400914 TI - Automatic Classification of Ultrasound Screening Examinations of the Abdominal Aorta. AB - Our work facilitates the identification of veterans who may be at risk for abdominal aortic aneurysms (AAA) based on the 2007 mandate to screen all veteran patients that meet the screening criteria. The main research objective is to automatically index three clinical conditions: pertinent negative AAA, pertinent positive AAA, and visually unacceptable image exams. We developed and evaluated a ConText-based algorithm with the GATE (General Architecture for Text Engineering) development system to automatically classify 1402 ultrasound radiology reports for AAA screening. Using the results from JAPE (Java Annotation Pattern Engine) transducer rules, we developed a feature vector to classify the radiology reports with a decision table classifier. We found that ConText performed optimally on precision and recall for pertinent negative (0.99 (0.98-0.99), 0.99 (0.99-1.00)) and pertinent positive AAA detection (0.98 (0.95-1.00), 0.97 (0.92-1.00)), and respectably for determination of non-diagnostic image studies (0.85 (0.77-0.91), 0.96 (0.91-0.99)). In addition, our algorithm can determine the AAA size measurements for further characterization of abnormality. We developed and evaluated a regular expression based algorithm using GATE for determining the three contextual conditions: pertinent negative, pertinent positive, and non diagnostic from radiology reports obtained for evaluating the presence or absence of abdominal aortic aneurysm. ConText performed very well at identifying the contextual features. Our study also discovered contextual trigger terms to detect sub-standard ultrasound image quality. Limitations of performance included unknown dictionary terms, complex sentences, and vague findings that were difficult to classify and properly code. PMID- 27400915 TI - Risk of Preeclampsia in Pregnancies After Assisted Reproductive Technology and Ovarian Stimulation. AB - Objective To compare the risk of preeclampsia among spontaneously conceived pregnancies to those after hyperestrogenic ovarian stimulation (hyperestrogenic OS) with and without assisted reproductive technology (ART), and stimulation with non-hyperestrogenic aromatase inhibitor stimulation (non-hyperestrogenic OS). Methods Live-born singleton deliveries among women 20-49 years were identified in the 2004-2012 Truven Health MarketScan Commercial Claims and Encounters Databases using ICD-9 and CPT codes. Maternal characteristics were compared using Chi squared and Fisher exact tests. We performed multilevel multivariable logistic regression, controlling for maternal age, parity, comorbid conditions, and region of delivery, and calculated adjusted odds ratios (aOR) and 95 % confidence intervals for mild and severe preeclampsia. Results 1,014,526 spontaneously conceived, 6881 hyperestrogenic OS with ART, 27,516 hyperestrogenic OS without ART, and 2117 non-hyperestrogenic OS pregnancies were identified. The adjusted odds of developing preeclampsia were increased for deliveries after hyperestrogenic OS with ART (mild preeclampsia aOR 1.42, 1.24-1.62; severe preeclampsia aOR 1.83, 1.59-2.11) and without ART (mild preeclampsia aOR 1.32, 1.24-1.42; severe preeclampsia aOR 1.53, 1.41-1.66). Adjusted odds of preeclampsia were similar between spontaneously conceived and non-hyperestrogenic OS pregnancies. Conclusions for Practice Risk of preeclampsia after ART may in part be related to supraphysiologic estrogen associated with hyperestrogenic OS. PMID- 27400916 TI - Screening for Post-traumatic Stress Disorder in Prenatal Care: Prevalence and Characteristics in a Low-Income Population. AB - Objectives Investigate the feasibility of using a brief, 4-item PTSD screening tool (PTSD-PC) as part of routine prenatal care in two community health care settings serving ethnically and linguistically diverse low-income populations. Report prevalence and differences by sub-threshold and clinical levels, in demographic, health, mental health, risk behaviors, and service use. Methods Women were screened as part of their prenatal intake visit over a 2-year period. Those screening positive at clinical or sub-threshold levels were recruited if they spoke English, Spanish, Portuguese, Vietnamese or Arabic. Enrolled women were interviewed about psychosocial risk factors, prior traumas, PTSD symptoms, depression, anxiety, substance use, health and services, using validated survey instruments. Results Of 1362 women seen for prenatal intakes, 1259 (92 %) were screened, 208 (17 %) screened positive for PTSD at clinical (11 %) or sub threshold levels (6 %), and 149 (72 % of all eligible women) enrolled in the study. Those screening positive were significantly younger, had more prior pregnancies, were less likely to be Asian or black, and were more likely to be non-English speakers. Enrolled women at clinical as compared to sub-threshold levels showed few differences in psychosocial risk, but had significantly more types of trauma, more trauma before age 18, more interpersonal trauma, and had greater depression, anxiety, and PTSD symptoms. Only about 25 % had received mental health treatment. Conclusions The PTSD-PC was a feasible screening tool for use in prenatal care. While those screening in at clinical levels were more symptomatic, those at subthreshold levels still showed substantial symptomology and psychosocial risk. PMID- 27400917 TI - Provider Advice and Women's Intentions to Meet Weight Gain, Physical Activity, and Nutrition Guidelines During Pregnancy. AB - OBJECTIVES: To determine the prevalence and accuracy of patient-reported provider advice on weight gain, physical activity, and nutrition during prenatal visits and to examine the associations of provider advice with women's behavioral intentions toward weight gain, physical activity, and nutrition. METHODS: A mixed methods study design was used to assess patient-report of provider advice and health intentions in women between 20 and 30 weeks gestation (n = 188). Bivariate analyses examined patient-reported provider advice on weight gain, physical activity, and nutrition with women's behavioral intentions. Linear and logistic regression models examined associations of provider weight gain recommendations with women's intended weight gain. RESULTS: Approximately 52 % of women reported provider advice on weight gain, 63 % on physical activity, and 56 % on nutrition. Of those who reported weight gain advice, 79 % cited provider recommendations within the Institute of Medicine guidelines, 9 % below, and 11 % above. Patient report of provider advice on physical activity and nutrition were consistent with guidelines, but limited in scope. Provider advice (yes/no) was significantly associated with women's intentions to meet physical activity (p = 0.01) and nutrition (p = 0.02), but not weight gain guidelines (p = 0.86). Provider recommended weight gain (pounds) was significantly associated with women's intended weight gain in linear and logistic regression models. CONCLUSIONS FOR PRACTICE: A large percentage of women report receiving no advice from providers on weight gain, physical activity or nutrition during pregnancy. Of those who receive advice, most report recommendations consistent with current guidelines. Provider advice was associated with women's weight gain, physical activity, and nutrition intentions in pregnancy. PMID- 27400918 TI - Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases. AB - Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a t(12;15)(p13;q25) resulting in an ETV6-NTRK3 fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland or breast primary; the clinico-pathologic characteristics are reviewed. Assessment for rearrangement of the ETV6 (12p13) locus was conducted by fluorescence in situ hybridization (FISH) on representative FFPE sections using an ETV6 break apart probe (Abbott Molecular, Des Plaines, IL, USA). The patients were two females (52 and 55 years-old) and 1 male (74 years-old). The tumors were poorly circumscribed solid white tan nodules involving the thyroid. Histologically, they were invasive and showed solid, microcystic, cribriform, and tubular growth patterns composed of variably bland polygonal eosinophilic cells with vesicular nuclear chromatin and conspicuous nucleoli. All three cases showed metastasis to lymph nodes; one case showed lateral neck involvement. The tumor cells were positive for S100 and mammaglobin. GATA-3 and PAX-8 were positive in 2 cases, one of which only focally so. All three cases were negative for TTF-1 and thyroglobulin. Rearrangement of the ETV6 locus was confirmed in all cases and a diagnosis of MASC rendered for each case. A site of origin distinct from the thyroid gland was not identified, with a median follow up of 24 months. MASC may rarely involve the thyroid gland. The origin of these lesions is unknown; while an origin from ectopic salivary gland type cells is entertained, a metastatic origin from an occult primary cannot be definitively excluded at this time. Given the histologic (follicular-like microcystic pattern with colloid-like secretions and papillary pattern), immunophenotypic (PAX-8), and even molecular overlap, MASC can be mistaken for papillary thyroid carcinoma and should be considered in the differential diagnosis of a thyroid mass. PMID- 27400919 TI - The application of virtual reality technology to understanding psychosis : Commentary on Valmaggia et al. (2016): using virtual reality to investigate psychological processes and mechanisms associated with the onset and maintenance of psychosis: a systematic review. PMID- 27400920 TI - Development of a sufficient and effective procedure for transformation of an oleaginous yeast, Rhodosporidium toruloides DMKU3-TK16. AB - Rhodosporidium toruloides DMKU3-TK16 (TK16), a basidiomycetous yeast isolated in Thailand, can produce a large amount of oil corresponding to approximately 70 % of its dry cell weight. However, lack of a sufficient and efficient transformation method makes further genetic manipulation of this organism difficult. We here developed a new transformation system for R. toruloides using a lithium acetate method with the Sh ble gene as a selective marker under the control of the R. toruloides ATCC 10657 GPD1 promoter. A linear DNA fragment containing the Sh ble gene expression cassette was integrated into the genome, and its integration was confirmed by colony PCR and Southern blot. Then, we further optimized the parameters affecting the transformation efficiency, such as the amount of linear DNA, the growth phase, the incubation time in the transformation mixture, the heat shock treatment temperature, the addition of DMSO and carrier DNA, and the recovery incubation time. With the developed method, the transformation efficiency of approximately 25 transformants/MUg DNA was achieved. Compared with the initial trial, transformation efficiency was enhanced 417-fold. We further demonstrated the heterologous production of EGFP in TK16 by microscopic observation and immunoblot analysis, and use the technique to disrupt the endogenous URA3 gene. The newly developed method is thus simple and time saving, making it useful for efficient introduction of an exogenous gene into R. toruloides strains. Accordingly, this new practical approach should facilitate the molecular manipulation, such as target gene introduction and deletion, of TK16 and other R. toruloides strains as a major source of biodiesel. PMID- 27400921 TI - Patient Perceptions of Electronic Medical Record Use by Faculty and Resident Physicians: A Mixed Methods Study. AB - BACKGROUND: While concerns remain regarding Electronic Medical Records (EMR) use impeding doctor-patient communication, resident and faculty patient perspectives post-widespread EMR adoption remain largely unexplored. OBJECTIVE: We aimed to describe patient perspectives of outpatient resident and faculty EMR use and identify positive and negative EMR use examples to promote optimal utilization. DESIGN: This was a prospective mixed-methods study. PARTICIPANTS: Internal medicine faculty and resident patients at the University of Chicago's primary care clinic participated in the study. APPROACH: In 2013, one year after EMR implementation, telephone interviews were conducted with patients using open ended and Likert style questions to elicit positive and negative perceptions of EMR use by physicians. Interview transcripts were analyzed qualitatively to develop a coding classification. Satisfaction with physician EMR use was examined using bivariate statistics. RESULTS: In total, 108 interviews were completed and analyzed. Two major themes were noted: (1) Clinical Functions of EMR and (2) Communication Functions of EMR; as well as six subthemes: (1a) Clinical Care (i.e., clinical efficiency), (1b) Documentation (i.e., proper record keeping and access), (1c) Information Access, (1d) Educational Resource, (2a) Patient Engagement and (2b) Physical Focus (i.e., body positioning). Overall, 85 % (979/1154) of patient perceptions of EMR use were positive, with the majority within the "Clinical Care" subtheme (n = 218). Of negative perceptions, 66 % (115/175) related to the "Communication Functions" theme, and the majority of those related to the "Physical Focus" subtheme (n = 71). The majority of patients (90 %, 95/106) were satisfied with physician EMR use: 59 % (63/107) reported the computer had a positive effect on their relationship and only 7 % (8/108) reported the EMR made it harder to talk with their doctors. CONCLUSIONS: Despite concerns regarding EMRs impeding doctor-patient communication, patients reported largely positive perceptions of the EMR with many patients reporting high levels of satisfaction. Future work should focus on improving doctors "physical focus" when using the EMR to redirect towards the patient. PMID- 27400922 TI - Case Management may Reduce Emergency Department Frequent use in a Universal Health Coverage System: a Randomized Controlled Trial. AB - BACKGROUND: Frequent emergency department (ED) users account for a disproportionately high number of ED visits. Studies on case management (CM) interventions to reduce frequent ED use have shown mixed results, and few studies have been conducted within a universal health coverage system. OBJECTIVE: To determine whether a CM intervention-compared to standard emergency care-reduces ED attendance. DESIGN: Randomized controlled trial. PARTICIPANTS: Two hundred fifty frequent ED users (5 or more visits in the prior 12 months) who visited a public urban ED at the Lausanne University Hospital between May 2012 and July 2013 were allocated to either an intervention (n = 125) or control (n = 125) group, and monitored for 12 months. INTERVENTIONS: An individualized CM intervention consisting of concrete assistance in obtaining income entitlements, referral to primary or specialty medical care, access to mental health care or substance abuse treatment, and counseling on at-risk behaviors and health care utilization (in addition to standard care) at baseline and 1, 3, and 5 months. MAIN MEASURES: We used a generalized linear model for count data (negative binomial distribution) to compare the number of ED visits during the 12-month follow-up between CM and usual care, from an intention-to-treat perspective. KEY RESULTS: At 12 months, there were 2.71 (+/-0.23) ED visits in the intervention group versus 3.35 (+/-0.32) visits among controls (ratio = 0.81, 95 % CI = 0.63; 1.02). In the multivariate model, the effect of the CM intervention on the number of ED visits approached statistical significance (b = -0.219, p = 0.075). The presence of poor social determinants of health was a significant predictor of ED use in the multivariate model (b = 0.280, p = 0.048). CONCLUSIONS: CM may reduce ED use by frequent users through an improved orientation to the health care system. Poor social determinants of health significantly increase use of the ED by frequent users. PMID- 27400923 TI - Experiences with POLST: Opportunities for Improving Advance Care Planning : Editorial & Comment on: "Use of Physician Orders for Life-Sustaining Treatment among California Nursing Home Residents". PMID- 27400924 TI - Bullosis Diabeticorum. PMID- 27400925 TI - Incidental Discovery of Retained Triple Lumen Catheter Guidewire. PMID- 27400926 TI - Capsule Commentary on Chiu et al. BMI Trajectories as a Harbinger of Pre-Diabetes or Underdiagnosed Diabetes: An 18-Year Retrospective Cohort Study in Taiwan. PMID- 27400927 TI - Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo. AB - Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment. It is unclear whether benzodiazepine induced cognitive impairment is reversible. Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add-on melatonin due to its anti-inflammatory and neuroprotective properties. We examined how melatonin and benzodiazepine withdrawal affect cognition, subjective well-being, and psychosocial functioning. Eighty patients with schizophrenia or bipolar disorder were randomized to add-on treatment once daily with either prolonged-release melatonin or placebo in a 24-week, double-blind clinical trial. All participants gradually tapered usual benzodiazepine dosage in a closely monitored treatment setting. We used the Brief Assessment of Cognition in Schizophrenia (BACS) to assess neurocognitive performance with additional assessments of subjective well being and psychosocial functioning. BACS composite and subscale scores (except motor speed) significantly improved in parallel with benzodiazepine dose reduction, but there was no additional effect of melatonin. Cognitive performance was still markedly impaired post-tapering compared with normative data. Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning. In conclusion, add-on melatonin does not seem to affect cognition, well-being, or psychosocial functioning in patients with severe mental illness. The observed improvement in cognitive performance could not be distinguished from retest effects, which may in turn have been facilitated by the benzodiazepine tapering. PMID- 27400928 TI - Sweat it out? The effects of physical exercise on cognition and behavior in children and adults with ADHD: a systematic literature review. AB - As attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed developmental disorders in childhood, effective yet safe treatment options are highly important. Recent research introduced physical exercise as a potential treatment option, particularly for children with ADHD. The aim of this review was to systematically analyze potential acute and chronic effects of cardio and non-cardio exercise on a broad range of functions in children with ADHD and to explore this in adults as well. Literature on physical exercise in patients with ADHD was systematically reviewed based on categorizations for exercise type (cardio versus non-cardio), effect type (acute versus chronic), and outcome measure (cognitive, behavioral/socio-emotional, and physical/(neuro)physiological). Furthermore, the methodological quality of the reviewed papers was addressed. Cardio exercise seems acutely beneficial regarding various executive functions (e.g., impulsivity), response time and several physical measures. Beneficial chronic effects of cardio exercise were found on various functions as well, including executive functions, attention and behavior. The acute and chronic effects of non-cardio exercise remain more questionable but seem predominantly positive too. Research provides evidence that physical exercise represents a promising alternative or additional treatment option for patients with ADHD. Acute and chronic beneficial effects of especially cardio exercise were reported with regard to several cognitive, behavioral, and socio emotional functions. Although physical exercise may therefore represent an effective treatment option that could be combined with other treatment approaches of ADHD, more well-controlled studies on this topic, in both children and adults, are needed. PMID- 27400929 TI - beta-Adrenergic receptor gene expression in HIV-associated neurocognitive impairment and encephalitis: implications for MOR-1K subcellular localization. AB - We previously reported that mRNA expression of the unique alternatively spliced OPRM1 isoform MU-opioid receptor-1K (MOR-1K), which exhibits excitatory cellular signaling, is elevated in HIV-infected individuals with combined neurocognitive impairment (NCI) and HIV encephalitis (HIVE). It has recently been shown that the beta2-adrenergic receptor (beta2-AR) chaperones MOR-1K, normally localized intracellularly, to the cell surface. Here, we found mRNA expression of the adrenoceptor beta 2 (ADRB2) gene is also elevated in NCI-HIVE individuals, as well as that beta2-AR protein expression is elevated in HIV-1-infected primary human astrocytes treated with morphine, and discuss the implications for MOR-1K subcellular localization in this condition. PMID- 27400930 TI - Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals. AB - HIV-associated neurocognitive disorders (HANDs) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNalpha) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNalpha and neurocognitive performance in ambulatory HIV-infected individuals with milder impairment. An eight-test neuropsychological battery representing six cognitive domains was administered. Individual scores were adjusted for demographic characteristics, and a composite neuropsychological score (NPT-8) was calculated. IFNalpha and CSF neurofilament light chain (NFL) levels were measured using enzyme-linked immunosorbent assay (ELISA). There were 15 chronically infected participants with a history of significant immunocompromise (median nadir CD4+ of 49 cells/MUl). Most participants were neurocognitively impaired (mean global deficit score of 0.86). CSF IFNalpha negatively correlated with three individual tests (Trailmaking A, Trailmaking B, and Stroop Color-Word) as well as the composite NPT-8 score (r = 0.67, p = 0.006). These negative correlations persisted in multivariable analyses adjusting for chronic hepatitis B and C. Additionally, CSF IFNalpha correlated strongly with CSF NFL, a marker of neuronal damage (rho = 0.748, p = 0.0013). These results extend findings from individuals with severe HIV-associated dementia in the pre-cART era and suggest that IFNalpha may continue to play a role in HAND pathogenesis during the cART era. Further investigation into the role of IFNalpha is indicated. PMID- 27400933 TI - A 10-Month-Old Male With a Cough, Fever, and Abnormal Hepatitis Serologies. PMID- 27400931 TI - Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status. AB - Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS). Our studies revealed unique associations between GDS and the presence of specific amino acid changes in peripheral blood-derived Vpr sequences [neuropsychological impairment Vpr (niVpr) variants]. Amino acids N41 and A55 in the Vpr sequence were associated with more pronounced neurocognitive deficits (higher GDS). In contrast, amino acids I37 and S41 were connected to measurably lower GDS. All niVpr variants were also detected in DNA isolated from HIV-1-infected brain tissues. The implication of these results is that niVpr variants alter the genesis and/or progression of HAND through differences in Vpr-mediated effects in the peripheral blood and/or the brain. PMID- 27400934 TI - Resident Notes in an Electronic Health Record. AB - Adoption of electronic health records (EHRs) has forced a transition in medical documentation, yet little is known about clinician documentation in the EHR. This study compares electronic inpatient progress notes written by residents pre- and post introduction of standardized note templates and investigates resident perceptions of EHR documentation. A total of 454 resident progress notes pre- and 610 notes post-template introduction were identified. Note length was 263 characters shorter ( P = .004) and mean end time was 73 minutes later ( P < .0001) with new template implementation. In subanalysis of 100 notes, the assessment and plan section was 46 words shorter with the new template ( P < .01). Among survey respondents, 89% liked the new note templates, 78% stated the new templates facilitated note completion. The resident focus group revealed ambivalence toward the EHR's contribution to note writing. Note templates resulted in shorter notes. Residents appreciate electronic note templates but are unsure if the EHR supports note writing overall. PMID- 27400932 TI - Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B. AB - A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV 1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n = 27) and C (n = 25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP 1alpha, MIP-1beta, RANTES, IP-10) and cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N = 19) using an independent group t test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p < 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27 vs. 0 %), subtypes B and C did not differ (32 and 22 %; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV. PMID- 27400935 TI - Characteristics of 1616 Consecutive Dog Bite Injuries at a Single Institution. AB - Dog bite injuries remain a common form of pediatric trauma. This single institution study of 1616 consecutive dog bite injuries over 4 years revealed a much higher prevalence of dog bites as compared with other similar centers. Though inpatient admission was rare (9.8%), 58% of all patients required laceration repair, primarily in the emergency department. Infants were more than 4 times as likely to be bitten by the family dog and more than 6 times as likely to be bitten in the head/neck region. Children <=5 years old were 62% more likely to require repair; and 5.5% of all patients required an operation. Pit bull bites were implicated in half of all surgeries performed and over 2.5 times as likely to bite in multiple anatomic locations as compared to other breeds. The relatively high regional prevalence and younger age of injured patients as compared with other centers is a topic of further study but should draw attention to interventions that can minimize child risk. PMID- 27400936 TI - Characteristics of Patients Who Survived < 3 Months or > 2 Years After Surgery for Spinal Metastases: Can We Avoid Inappropriate Patient Selection? AB - PURPOSE: Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is < 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. PATIENTS AND METHODS: A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS]), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. RESULTS: In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. CONCLUSION: Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival. PMID- 27400937 TI - Association of Chromosome 1q Gain With Inferior Survival in Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group. AB - PURPOSE: The goal of this study was to analyze the association of copy number gain of 1q in favorable-histology Wilms tumors (FHWTs) with event-free survival (EFS) and overall survival (OS) within each tumor stage and with 1p and 16q copy number loss and/or loss of heterozygosity. METHODS: Unilateral FHWTs from 1,114 patients enrolled in National Wilms Tumor Study-5 that were informative for 1p and 16q microsatellite markers (previously determined) and informative for 1q gain, 1p loss, and 16q loss using multiplex ligation-dependent probe amplification were analyzed. RESULTS: Eight-year EFS was 86% (95% CI, 84% to 88%) for the entire cohort. Of 1,114 patients, 317 tumors (28%) displayed 1q gain. Eight-year EFS was 77% for those with 1q gain and 90% for those lacking 1q gain (P < .001). Eight-year OS was 88% for those with 1q gain and 96% for those lacking 1q gain (P < .001). Within each disease stage, 1q gain was associated with inferior EFS (stage I, 85% v 95%; P = .0052; stage II, 81% v 87%; P = .0775; stage III, 79% v 89%; P = .01; stage IV, 64% v 91%; P = .001). OS was significantly inferior in patients with stage I (P < .0015) and stage IV disease (P = .011). With multivariable analysis, 1q gain was associated with an increased relative risk of relapse of 2.4 (P < .001), whereas 1p loss was not, despite significance on univariable analysis. CONCLUSION: Gain of 1q is associated with inferior survival in unilateral FHWTs and may be used to guide risk stratification in future studies. PMID- 27400938 TI - 2016 ASCO Presidential Address: "Collective Wisdom: The Future of Patient Centered Care and Research". PMID- 27400940 TI - Should We Use Adjuvant Chemotherapy for Muscle-Invasive Bladder Cancer After Radical Cystectomy? PMID- 27400941 TI - Reply to E.M. Ruggeri et al and Y.-W. Hu. PMID- 27400939 TI - Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. AB - Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis <= 10 * 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate risk APL. PMID- 27400942 TI - Outcome of Patients With Recurrent Osteosarcoma Enrolled in Seven Phase II Trials Through Children's Cancer Group, Pediatric Oncology Group, and Children's Oncology Group: Learning From the Past to Move Forward. AB - PURPOSE: The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. PATIENTS AND METHODS: We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. RESULTS: In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). CONCLUSION: The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma. PMID- 27400943 TI - Umbilical Cord Blood-Derived Mesenchymal Stromal Cells for Reducing Chronic Graft Versus-Host Disease After Haploidentical Transplantation: Just Another Labor Intensive Strategy, or Showing the Way? PMID- 27400944 TI - Barriers to Quality End-of-Life Care for Patients With Blood Cancers. AB - PURPOSE: Patients with blood cancers have been shown to receive suboptimal care at the end of life (EOL) when assessed with standard oncology quality measures (eg, no chemotherapy <= 14 days before death). As they were developed primarily for solid tumors, it is unclear if these measures are appropriate for patients with hematologic malignancies. Moreover, barriers to high-quality EOL care for this specific patient population are largely unknown. METHODS: In 2015, we asked a national cohort of hematologic oncologists about the acceptability of eight standard EOL quality measures. Building on prior qualitative work, we prespecified that measures achieving agreement among at least 55% of respondents would be considered acceptable. We also explored perspectives regarding barriers to quality EOL care. RESULTS: We received 349 surveys (response rate = 57.3%). Six of the standard measures met the threshold of acceptability, and four were acceptable to > 75% of respondents: hospice admission > 7 days before death, no chemotherapy <= 14 days before death, no intubation in the last 30 days of life, and no cardiopulmonary resuscitation in the last 30 days of life. The highest ranked barriers to quality EOL care reported were "unrealistic patient expectations" (97.3%), "clinician concern about taking away hope" (71.3%), and "unrealistic clinician expectations" (59.0%). CONCLUSION: In this large national cohort of hematologic oncologists, standard EOL quality measures were highly acceptable. The top barrier to quality EOL care reported was unrealistic patient expectations, which may be best addressed with more timely and effective advance care discussions. PMID- 27400945 TI - Oncologist's Guilt. PMID- 27400946 TI - Raising the Bar for Therapeutic Trials in Advanced Prostate Cancer. PMID- 27400947 TI - Phase III Study of Cabozantinib in Previously Treated Metastatic Castration Resistant Prostate Cancer: COMET-1. AB - PURPOSE: Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. RESULTS: A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). CONCLUSION: Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes. PMID- 27400948 TI - Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial. AB - PURPOSE: Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC. PATIENTS AND METHODS: Six hundred sixty seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m(2) on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m(2) plus carboplatin area under the curve 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression-free survival. Secondary end points were overall survival, overall response rate, and adverse events. RESULTS: Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC. CONCLUSION: No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC. PMID- 27400950 TI - Real-World Role of Adjuvant Chemotherapy in Bladder Cancer. PMID- 27400949 TI - Phase II Multicenter, Randomized, Double-Blind Controlled Study of Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cells in the Prophylaxis of Chronic Graft-Versus-Host Disease After HLA-Haploidentical Stem-Cell Transplantation. AB - PURPOSE: Although mesenchymal stromal cells (MSCs) possess immunomodulatory properties and exhibit promising efficacy against chronic graft-versus-host disease (cGVHD), little is known about the efficacy of MSCs in the prophylaxis of cGVHD after HLA-haploidentical hematopoietic stem-cell transplantation (HLA-haplo HSCT). PATIENTS AND METHODS: In this multicenter, double-blind, randomized controlled trial, we investigated the incidence and severity of cGVHD among patients, and the changes in T, B, and natural killer (NK) cells after the repeated infusion of MSCs. RESULTS: The 2-year cumulative incidence of cGVHD in the MSCs group was 27.4% (95% CI, 16.2% to 38.6%), compared with 49.0% (95% CI, 36.5% to 61.5%) in the non-MSCs control group (P = .021). Seven patients in the non-MSCs control group had severe lung cGVHD, but no patients in the MSCs group developed typical lung cGVHD (P = .047). After the MSC infusions, increasing memory B lymphocytes and regulatory T cells, as well as the ratio of type 1 T helper to type 2 T helper cells, were observed, whereas the number of NK cells decreased. CONCLUSION: Our findings suggest that the repeated infusion of MSCs might inhibit cGVHD symptoms in patients after HLA-haplo HSCT, accompanied by changes in the numbers and subtypes of T, B, and NK cells, leading to the acquisition of immune tolerance. PMID- 27400951 TI - Adrenomedullin predicts high risk and culture positivity in children with solid tumors suffering from neutropenic fever. AB - AIM OF STUDY: Neutropenic fever is a source of morbidity and mortality in children with cancer. It is not possible to detect the causative agent in cultures in most cases; the research for a marker that can show the severity of the disease is ongoing. We evaluated the role of adrenomedullin (ADM) at predicting prognosis on patients with febrile neutropenia, which has been proven to be a good prognostic marker for diseases with high morbidity and mortality, such as heart failure, ischemic ventricular dysfunction, sepsis, and systemic inflammatory response syndrome. MATERIALS AND METHODS: We recorded the 36 febrile episodes of 14 children receiving chemotherapy due to solid tumors. There were 10 events with unknown origin in the low-risk group, while in the high-risk group, there were 17 events with unknown origin, 8 events with microbiological origin and 1 event with clinically proven infection. Cultures were positive only in the high-risk group. However, the changes of ADM levels through time periods (first, second, third, and seventh days) were not significant. RESULTS: The first-day plasma ADM levels significantly predicted the presence of culture positivity (AUC 0.628, 95% CI 0.40-0.85, p = 0.303) and high-risk patients with neutropenic fever (AUC 0.76, 95% CI 0.56-0.97, p = 0.016). CONCLUSION: Our study showed that increased plasma ADM was correlated with high-risk neutropenic fever and culture positivity. The ADM levels in the high-risk group were clearly high at the diagnosis and continued to the end of the treatment. PMID- 27400952 TI - The anti-metastatic micro-environment of the bone: Importance of osteocyte Cx43 hemichannels. AB - Bone metastases of tumor cells are a common and life-threatening feature of a variety of late-stage cancers, including breast cancers. However, until now, much less has been known about the intrinsic anti-metastatic properties of the bones and how these could be exploited to prevent or treat bone metastases. Very recently, native Cx43 hemichannels present in osteocytes have been identified as important anti-metastatic signaling complexes by establishing high local extracellular ATP levels. Moreover, bisphosphonate drugs, applied as adjuvant therapies in the treatment of breast cancer patients and bone diseases, are known to display anti-metastatic properties. Now, it became clear that these compounds exert their effects through osteocyte Cx43 hemichannels, thereby triggering their opening and promoting ATP release in the extracellular micro-environment. Hence, endogenous osteocyte Cx43 hemichannels emerge as important and promising therapeutic targets for the prevention of bone metastases and/or clinical treatment of bone-metastasized breast cancers. PMID- 27400953 TI - Electrons Mediate the Gas-Phase Oxidation of Formic Acid with Ozone. AB - Gas-phase reactions of CO3 (.-) with formic acid are studied using Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Signal loss indicates the release of a free electron, with the formation of neutral reaction products. This is corroborated by adding traces of SF6 to the reaction gas, which scavenges 38 % of the electrons. Quantum chemical calculations of the reaction potential energy surface provide a reaction path for the formation of neutral carbon dioxide and water as the thermochemically favored products. From the literature, it is known that free electrons in the troposphere attach to O2 , which in turn transfer the electron to O3 . O3 (.-) reacts with CO2 to form CO3 (.-) . The reaction reported here formally closes the catalytic cycle for the oxidation of formic acid with ozone, catalyzed by free electrons. PMID- 27400954 TI - Development of a duplex lateral flow assay for simultaneous detection of antibodies against African and Classical swine fever viruses. AB - Classical swine fever (CSF) and African swine fever (ASF) are both highly contagious diseases of domestic pigs and wild boar and are clinically indistinguishable. For both diseases, antibody detection is an integral and crucial part of prevention and control measures. The purpose of our study was to develop and initially validate a duplex pen-side test for simultaneous detection and differentiation of specific antibodies against CSF virus (CSFV) and ASF virus (ASFV). The test was based on the major capsid protein VP72 of ASFV and the structural protein E2 of CSFV, both considered the most immunogenic proteins of these viruses. The performance of the pen-side test was evaluated using a panel of porcine samples consisting of experimental, reference, and field sera, with the latter collected from European farms free of both diseases. The new lateral flow assay was able to detect specific antibodies to ASFV or CSFV, showing good levels of sensitivity and specificity. These preliminary data indicate the potential of the newly developed pen-side test for rapid differential detection of antibodies found in the 2 diseases, which is of particular importance in the field and in front-line laboratories where equipment and skilled personnel are limited and control of ASF and CSF is crucial. PMID- 27400955 TI - Validation of a gauze sponge sampling methodology to detect Tritrichomonas foetus by real-time PCR. AB - Bovine trichomoniasis is a concern for the cattle industry. Advances in testing systems have increased the ability to detect the disease in bulls. However, the greatest limitation is proper collection of an adequate sample. The low repeatability observed with most sample collection techniques can cause false negative results. The aim of our study was to validate a sample collection technique that increases diagnostic sensitivity and is easier and safer to collect than preputial scraping. Commercial bulls (n = 111) of unknown infection status were sampled for detection of Tritrichomonas foetus using 2 different collection methods: 1) preputial scraping with a dry insemination pipette and 2) penile sponging with a 16-ply gauze sponge. Preputial scraping samples were collected by vigorously scraping preputial and penile mucosa using a rigid insemination pipette while applying negative pressure with a syringe. Penile sponge samples were obtained by swabbing the penile and preputial mucosa with a gauze sponge during full extension of the penis. All samples were processed using a commercial medium and submitted under similar conditions for PCR testing. Positive PCR results were detected in 37 of 111 (33%) bulls using the preputial scraping technique; however, 39 of 111 (35%) were positive using the penile sponging technique. The Newton-Raphson algorithm predicted that the sensitivity of the preputial scraping method was 0.919 (95% CI: 0.689-0.983) and the sensitivity of the penile sponging was 0.949 (95% CI: 0.818-0.987). These data indicate that the penile sponging technique is a reliable alternative to the preputial scraping method. PMID- 27400956 TI - Infectious agents identified in aborted swine fetuses in a high-density breeding area: a three-year study. AB - Reproductive failure in sows is one of the most important factors affecting pig breeding. Many reproductive disorders are linked to both environmental factors and infectious agents. The goal of our study was to determine the presence of pathogens that are known to cause abortion, considering a set of conditioning factors, such as seasonality and pregnancy period. A large number of aborted fetuses (1,625 fetuses from 140 farms) from a high-density breeding area in northern Italy was analyzed for a period of 3 years. The pigs were diagnosed based on direct (culture, PCR) or indirect (enzyme-linked immunosorbent assay) evidence. An infectious etiologic agent was found in 323 of 549 cases of abortion (58.8%). These included viral agents (Porcine circovirus-2, 138/323; Porcine reproductive and respiratory syndrome virus, 108/323; porcine parvovirus, 20/323; pseudorabies virus, 6/323; and Encephalomyocarditis virus, 3/323) and bacteria (Escherichia coli, 64/323; Streptococcus sp., 63/323; Staphylococcus sp., 5/323; Pasteurella sp., 3/323; Shigella sp., 1/323; and Yersinia sp., 1/323). This study describes the prevalence of infectious agents involved in reproductive failure in a high-density swine population. The data can be useful to swine breeders, practitioners, and medical specialists in monitoring animal health and in supervising the breeding process. PMID- 27400957 TI - Characterization of a novel Canine distemper virus causing disease in wildlife. AB - Canine distemper virus (CDV) is a common cause of a multisystemic disease in both domestic dogs and wildlife species, including raccoons and foxes. Outbreaks of CDV in domestic dogs in eastern Tennessee have occurred since 2012, and it was determined that these outbreaks resulted from a novel genotype of CDV. We hypothesized that this virus is also infecting area wildlife and may be a source of the virus for these outbreaks in dogs. From 2013 to 2014, autopsies were performed and tissues collected from raccoons (Procyon lotor; n = 50) and gray foxes (Urocyon cinereoargenteus; n = 8) for CDV testing. A real-time reverse transcription PCR was used to document the presence of CDV in tissue samples, and a portion of the virus was subsequently sequenced for phylogenetic analysis. A high percentage of wildlife, both with (86%) and without (55%) clinical signs, tested positive for CDV, with the majority (77%) testing positive for the novel genotype. Microscopic findings, including syncytia in the lungs and viral inclusion bodies in urothelium, astrocytes, neurons, and bronchiolar epithelium, were also consistent with canine distemper. Minimal inflammation in the central nervous system of affected animals was indicative of the acute neurologic form of the disease. Pneumonia and parasitism were also commonly found in CDV-infected animals. Based on these results, CDV appears to be prevalent in eastern Tennessee wildlife. Subclinical or clinically recovered shedders are a potential source of this novel genotype for domestic dogs, and this genotype is genetically distinct from vaccine strains. PMID- 27400958 TI - Resolving Bovine viral diarrhea virus subtypes from persistently infected U.S. beef calves with complete genome sequence. AB - Bovine viral diarrhea virus (BVDV) is classified into 2 genotypes, BVDV-1 and BVDV-2, each of which contains distinct subtypes with genetic and antigenic variation. To effectively control BVDV by vaccination, it is important to know which subtypes of the virus are circulating and how their prevalence is changing over time. Accordingly, the purpose of our study was to estimate the current prevalence and diversity of BVDV subtypes from persistently infected (PI) beef calves in the central United States. Phylogenetic analysis of the 5'-UTR (5' untranslated region) for 119 virus strains revealed that a majority (82%) belonged to genotype 1b, and the remaining strains were distributed between genotypes 1a (9%) and 2 (8%); however, BVDV-2 subtypes could not be confidently resolved. Therefore, to better define the variability of U.S. BVDV isolates and further investigate the division of BVDV-2 isolates into subtypes, complete genome sequences were obtained for these isolates as well as representatives of BVDV-1a and -1b. Phylogenetic analyses of the complete coding sequence provided more conclusive genetic classification and revealed that U.S. BVDV-2 isolates belong to at least 3 distinct genetic groups that are statistically supported by both complete and individual coding gene analyses. These results show that a more complex set of BVDV-2 subtypes has been circulating in this region than was previously thought. PMID- 27400959 TI - Impact of region-of-interest method on quantitative analysis of DTI data in the optic tracts. AB - BACKGROUND: To extract DTI parameters from a specific structure, a region of interest (ROI) must be defined. ROI selection in small structures is challenging; the final measurement results could be affected due to the significant impact of small geometrical errors. In this study the optic tracts were analyzed with the aim to assess differences in DTI parameters due to ROI method and to identify the most reliable method. METHODS: Images of 20 healthy subjects were acquired. Fractional anisotropy (FA) was extracted from the optic tracts by four different ROI methods. Manual tracing was performed in 1) the b0 image and 2) a T1-weighted image registered to the FA image. Semi-automatic segmentation was performed based on 3) tractography and 4) the FA-skeleton algorithm in the tract-based spatial statistics (TBSS) framework. Results were analyzed with regard to ROI method as well as to inter-scan, intra-rater and inter-rater reliability. RESULTS: The resulting FA values divided the ROI methods into two groups that differed significantly: 1) the FA-skeleton and the b0 methods showed higher FA values compared to 2) the tractography and the T1-weighted methods. The intra- and inter rater variabilities were similar for all methods, except for the tractography method where the inter-rater variability was higher. The FA-skeleton method had a better reproducibility than the other methods. CONCLUSION: Choice of ROI method was found to be highly influential on FA values when the optic tracts were analyzed. The FA-skeleton method performed the best, yielding low variability and high repeatability. PMID- 27400960 TI - PREPARE: Pre-surgery physiotherapy for patients with degenerative lumbar spine disorder: a randomized controlled trial protocol. AB - BACKGROUND: Current guidelines for the management of patients with specific low back pain pathology suggest non-surgical intervention as first-line treatment, but there is insufficient evidence to make recommendations of the content in the non-surgical intervention. Opinions regarding the dose of non-surgical intervention that should be trialled prior to decision making about surgery intervention vary. The aim of the present study is to investigate if physiotherapy administrated before surgery improves function, pain and health in patients with degenerative lumbar spine disorder scheduled for surgery. The patients are followed over two years. A secondary aim is to study what factors predict short and long term outcomes. METHODS: This study is a single blinded, 2 arm, randomized controlled trial with follow-up after the completion of pre surgery intervention as well as 3, 12 and 24 months post-surgery. The study will recruit men and women, 25 to 80 years of age, scheduled for surgery due to; disc herniation, spinal stenosis, spondylolisthesis or degenerative disc disease. A total of 202 patients will be randomly allocated to a pre-surgery physiotherapy intervention or a waiting list group for 9 weeks. The waiting-list group will receive standardized information about surgery, post-surgical rehabilitation and advice to stay active. The pre-surgery physiotherapy group will receive physiotherapy 2 times per week, consisting of a stratified classification treatment, based on assessment findings. One of the following treatments will be selected; a) Specific exercises and mobilization, b) Motor control exercises or c) Traction. The pre-surgery physiotherapy group will also be prescribed a tailor made general supervised exercise program. The physiotherapist will use a behavioral approach aimed at reducing patient fear avoidance and increasing activity levels. They will also receive standardized information about surgery, post-surgical rehabilitation and advice to stay active. Primary outcome measure is Oswestry Disability Index. Secondary outcome measures are the visual analogue scale for back and leg pain, pain drawing, health related quality of life, Hospital anxiety and depression scale, Fear avoidance beliefs questionnaire, Self efficacy scale and Work Ability Index. DISCUSSION: The study findings will help improve the treatment of patients with degenerative lumbar spine disorder scheduled for surgery. TRIAL REGISTRATION: ClinicalTrials.gov reference: NCT02454400 (Trial registration date: August 31st 2015) and has been registered on ClinicalTrials.gov, identifier: NCT02454400 . PMID- 27400962 TI - Erratum to Description of Proteiniphilum saccharofermentans sp. nov., Petrimonas mucosa sp. nov. and Fermentimonas caenicola gen. nov., sp. nov., isolated from mesophilic laboratory-scale biogas reactors, and emended description of the genus Proteiniphilum. PMID- 27400963 TI - "Making a difference" - Medical students' opportunities for transformational change in health care and learning through quality improvement projects. AB - BACKGROUND: Quality improvement is increasingly becoming an essential aspect of the medical curriculum, with the intention of improving the health care system to provide better health care. The aim of this study was to explore undergraduate medical students' experiences of their involvement in quality improvement projects during a district health rotation. METHODS: Student group reports from rotations in learning centres of the University of Pretoria in Mpumalanga Province, South Africa were analysed for the period 2012 to 2015. Interviews were conducted with health care providers at four learning centres in 2013. RESULTS: Three main themes were identified: (1) 'Situated learning', describing students' exposure to the discrepancies between ideal and reality in a real-life situation and how they learned to deal with complex situations, individually and as student group; (2) 'Facing dilemmas', describing how students were challenged about the non-ideal reality; (3) 'Making a difference', describing the impact of the students' projects, with greater understanding of themselves and others through working in teams but also making a change in the health care system. CONCLUSION: Quality improvement projects can provide an opportunity for both the transformation of health care and for transformative learning, with individual and 'collective' self-authorship. PMID- 27400964 TI - Revisiting overexpression of a heterologous beta-glucosidase in Trichoderma reesei: fusion expression of the Neosartorya fischeri Bgl3A to cbh1 enhances the overall as well as individual cellulase activities. AB - BACKGROUND: The filamentous fungus Trichoderma reesei has the capacity to secret large amounts of cellulase and is widely used in a variety of industries. However, the T. reesei cellulase is weak in beta-glucosidase activity, which results in accumulation of cellobiose inhibiting the endo- and exo-cellulases. By expressing an exogenous beta-glucosidase gene, the recombinant T. reesei cellulase is expected to degrade cellulose into glucose more efficiently. RESULTS: The thermophilic beta-glucosidase NfBgl3A from Neosartorya fischeri is chosen for overexpression in T. reesei due to its robust activity. In vitro, the Pichia pastoris-expressed NfBgl3A aided the T. reesei cellulase in releasing much more glucose with significantly lower amounts of cellobiose from crystalline cellulose. The NfBgl3A gene was hence fused to the cbh1 structural gene and assembled between the strong cbh1 promoter and cbh1 terminator to obtain pRS NfBgl3A by using the DNA assembler method. pRS-NfBgl3A was transformed into the T. reesei uridine auxotroph strain TU-6. Six positive transformants showed beta glucosidase activities of 2.3-69.7 U/mL (up to 175-fold higher than that of wild type). The largely different beta-glucosidase activities in the transformants may be ascribed to the gene copy numbers of NfBgl3A or its integration loci. The T. reesei-expressed NfBgl3A showed highly similar biochemical properties to that expressed in P. pastoris. As expected, overexpression of NfBgl3A enhanced the overall cellulase activity of T. reesei. The CBHI activity in all transformants increased, possibly due to the extra copies of cbh1 gene introduced, while the endoglucanase activity in three transformants also largely increased, which was not observed in any other studies overexpressing a beta-glucosidase. NfBgl3A had significant transglycosylation activity, generating sophorose, a potent cellulase inducer, and other oligosaccharides from glucose and cellobiose. CONCLUSIONS: We report herein the successful overexpression of a thermophilic N. fischeri beta glucosidase in T. reesei. In the same time, the fusion of NfBgl3A to the cbh1 gene introduced extra copies of the cellobiohydrolase 1 gene. As a result, we observed improved beta-glucosidase and cellobiohydrolase activity as well as the overall cellulase activity. In addition, the endoglucanase activity also increased in some of the transformants. Our results may shed light on design of more robust T. reesei cellulases. PMID- 27400961 TI - The role of peptides in bone healing and regeneration: a systematic review. AB - BACKGROUND: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. METHODS: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. RESULTS: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. CONCLUSION: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge. PMID- 27400965 TI - Long-term exposure to PGE2 causes homologous desensitization of receptor-mediated activation of protein kinase A. AB - BACKGROUND: Acute exposure to prostaglandin E2 (PGE2) activates EP receptors in sensory neurons which triggers the cAMP-dependent protein kinase A (PKA) signaling cascade resulting in enhanced excitability of the neurons. With long term exposure to PGE2, however, the activation of PKA does not appear to mediate persistent PGE2-induced sensitization. Consequently, we examined whether homologous desensitization of PGE2-mediated PKA activation occurs after long-term exposure of isolated sensory neurons to the eicosanoid. METHODS: Sensory neuronal cultures were harvested from the dorsal root ganglia of adult male Sprague-Dawley rats. The cultures were pretreated with vehicle or PGE2 and used to examine signaling mechanisms mediating acute versus persistent sensitization by exposure to the eicosanoid using enhanced capsaicin-evoked release of immunoreactive calcitonin gene-related peptide (iCGRP) as an endpoint. Neuronal cultures chronically exposed to vehicle or PGE2 also were used to study the ability of the eicosanoid and other agonists to activate PKA and whether long-term exposure to the prostanoid alters expression of EP receptor subtypes. RESULTS: Acute exposure to 1 MUM PGE2 augments the capsaicin-evoked release of iCGRP, and this effect is blocked by the PKA inhibitor H-89. After 5 days of exposure to 1 MUM PGE2, administration of the eicosanoid still augments evoked release of iCGRP, but the effect is not attenuated by inhibition of PKA or by inhibition of PI3 kinases. The sensitizing actions of PGE2 after acute and long-term exposure were attenuated by EP2, EP3, and EP4 receptor antagonists, but not by an EP1 antagonist. Exposing neuronal cultures to 1 MUM PGE2 for 12 h to 5 days blocks the ability of PGE2 to activate PKA. The offset of the desensitization occurs within 24 h of removal of PGE2 from the cultures. Long-term exposure to PGE2 also results in desensitization of the ability of a selective EP4 receptor agonist, L902688 to activate PKA, but does not alter the ability of cholera toxin, forskolin, or a stable analog of prostacyclin to activate PKA. CONCLUSIONS: Long term exposure to PGE2 results in homologous desensitization of EP4 receptor activation of PKA, but not to neuronal sensitization suggesting that activation of PKA does not mediate PGE2-induced sensitization after chronic exposure to the eicosanoid. PMID- 27400966 TI - A randomized controlled trial of directive and nondirective smoking cessation coaching through an employee quitline. AB - BACKGROUND: Telephone quitlines can help employees quit smoking. Quitlines typically use directive coaching, but nondirective, flexible coaching is an alternative. Call-2-Quit used a worksite-sponsored quitline to compare directive and nondirective coaching modes, and evaluated employee race and income as potential moderators. METHODS: An unblinded randomized controlled trial compared directive and nondirective telephone coaching by trained laypersons. Participants were smoking employees and spouses recruited through workplace smoking cessation campaigns in a hospital system and affiliated medical school. Coaches were four non-medical women trained to use both coaching modes. Participants were randomized by family to coaching mode. Participants received up to 7 calls from coaches who used computer assisted telephone interview software to track topics and time. Outcomes were reported smoking abstinence for 7 days at last contact, 6 or 12 months after coaching began. Both worksites implemented new tobacco control policies during the study. RESULTS: Most participants responded to an insurance incentive introduced at the hospital. Call-2-Quit coached 518 participants: 22 % were African-American; 45 % had incomes below $30,000. Income, race, and intervention did not affect coaching completion rates. Cessation rates were comparable with directive and nondirective coaching (26 % versus 30 % quit, NS). A full factorial logistic regression model identified above median income (odds ratio = 1.8, p = 0.02), especially among African Americans (p = 0.04), and recent quit attempts (OR = 1.6, p = 0.03) as predictors of cessation. Nondirective coaching was associated with high cessation rates among subgroups of smokers reporting income above the median, recent quit attempts, or use of alternative therapies. Waiting up to 4 weeks to start coaching did not affect cessation. Of 41 highly addicted or depressed smokers who had never quit more than 30 days, none quit. CONCLUSION: Nondirective coaching improved cessation rates for selected smoking employees, but less expensive directive coaching helped most smokers equally well, regardless of enrollment incentives and delays in receiving coaching. Some subgroups had very low cessation rates with either mode of quitline support. TRIAL REGISTRATION: ClinicalTrials.gov NCT02730260 , Registered March 31, 2016. PMID- 27400967 TI - The elusive predisposition to mycoheterotrophy in Ericaceae. PMID- 27400968 TI - Antimicrobial potential of consolidation polymers loaded with biological copper nanoparticles. AB - BACKGROUND: Biodeterioration of historic monuments and stone works by microorganisms takes place as a result of biofilm production and secretion of organic compounds that negatively affect on the stone matrix. METHODS: Copper nanoparticles (CuNPs) were prepared biologically using the headspace gases generated by the bacterial culture Escherichia coli Z1. The antimicrobial activity of CuNPs was evaluated against the bacterial strains Bacillus subtilis, Micrococcus luteus, Streptomyces parvulus, Escherichia coli, Pseudomonas aeruginosa as well as some fungal strains Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Fusarium solani and Alternaria solani. RESULTS: Biological CuNPs demonstrated antibacterial and antifungal activities higher than those of the untreated copper sulfate. At the same time, limestone and sandstone blocks treated with consolidation polymers functionalized with CuNPs recorded apparent antimicrobial activity against E. coli, S. parvulus and B. subtilis in addition to an improvement in the physical and mechanical characters of the treated stones. Furthermore, the elemental composition of CuNPs was elucidated using electron dispersive x-ray system connected with the scanning electron microscope. CONCLUSION: Consolidation polymers impregnated with CuNPs could be used to restrain microbial deterioration in addition to the refinement of physico mechanical behavior of the historic stones. PMID- 27400970 TI - Prospectives of Antihypertensive Nano-ceuticals as Alternative Therapeutics. AB - BACKGROUND: Global death rate due to cardiovascular diseases (CVDs) is highest as compared to other ailments. Principal risk factor associated with CVDs is hypertension. Major classes of current antihypertensive (AHT) therapies include angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). All these antihypertensive therapeutic drugs have low oral bioavailability and can induce upper respiratory tract abstraction, angioedema, reflex tachycardia and extreme hypotensive effect after oral administration which can cause lethal effects in patients with heart diseases. OBJECTIVE: Controlled and targeted release by using antihypertensive nano-medicines can provide better solution to overcome above-mentioned side effects. RESULTS: Scientific evolution towards the development of biopolymer based nano-carrier systems has unlocked new horizons for safe and/or edible nano drug delivery systems. In this article, we have reviewed in detail various mechanisms of AHT drugs, major draw backs associated with current therapeutic strategies, and the advantages of AHT nano-medicines over conventional drugs. Furthermore, recent reports of bio-based nano/micro -carrier systems with different AHT drugs have been analyzed with their key features. In depth review has been presented for chitosan as a potential carrier of AHT drugs due to its distinctive properties comprising muco-adhesive attribute, permeation enhancement as well as its biocompatible and biodegradable nature. CONCLUSION: Chitosan based novel AHT nano-ceuticals can improve oral bioavailability, reduce hydrophobicity and increase the plasma half-life of AHT drugs by their sustained release in lower part of the GIT. PMID- 27400969 TI - Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy. AB - BACKGROUND: Estimating distant recurrence (DR) risk among women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative early breast cancer helps decisions on using adjuvant chemotherapy. The 21-gene Oncotype DX recurrence score (RS) is widely used for this. EndoPredict (EPclin) is an alternative test combining prognostic information from an eight-gene signature (EP score) with tumor size and nodal status. We compared the prognostic information provided by RS and EPclin for 10-year DR risk. METHODS: We used likelihood ratio chi2 and Kaplan-Meier survival analyses to compare prognostic information provided by EP, EPclin, RS, and the clinical treatment score (CTS) of clinicopathologic parameters in 928 patients with ER+ disease treated with five years' anastrozole or tamoxifen. Comparisons were made for early (0-5 years) and late (5-10 years) DR according to nodal status. All statistical tests were two sided. RESULTS: In the overall population, EP and EPclin provided substantially more prognostic information than RS (LRchi(2): EP = 49.3; LRchi(2): EPclin = 139.3; LRchi(2): RS = 29.1), with greater differences in late DR and in node positive patients. EP and EPclin remained statistically significantly prognostic when adjusted for RS (DeltaLRchi(2): EP+RS vs RS = 20.2; DeltaLRchi(2): EPclin+RS vs RS = 113.8). Using predefined cut-offs, EPclin and RS identified 58.8% and 61.7% patients as low risk, with hazard ratios for non-low vs low risk of 5.99 (95% confidence interval [CI] = 3.94 to 9.11) and 2.73 (95% CI = 1.91 to 3.89), respectively. CONCLUSIONS: EP and EPclin were highly prognostic for DR in endocrine-treated patients with ER+, HER2-negative disease. EPclin provided more prognostic information than RS. This was partly but not entirely because of EPclin integrating molecular data with nodal status and tumor size. PMID- 27400971 TI - Withdrawn: Paroxysmal Nocturnal Hemoglobinuria: The Future Of Complement-Based Therapies. AB - Withdrawn by the publisher. PMID- 27400972 TI - A Central Role for ATP Signalling in Glial Interactions in the CNS. AB - The purine ATP has a prominent regulatory role in CNS function and pathology due to its actions on glial cells - microglia, astrocytes and oligodendrocytes. ATP serves as an apparently ubiquitous 'gliotransmitter' that is released by astrocytes and other cells to activate purine receptors on neighbouring cells. In pathology, the release of ATP mediates both tissue damage and repair by its direct effects on glial cell integrity and survival. The actions of ATP on glia are mediated via a wide range of receptors, broadly divided into ionotropic P2X and metabotropic (G-protein coupled receptors (GPCR)) P2Y receptors, of which there are multiple subtypes (P2X1-P2X7 and P2Y1-P2Y14). ATP-mediated interactions between astrocytes and microglia are at the centre of immune responses in the CNS, with prominent roles for the P2X4, P2X7, P2Y1, P2Y6 and P2Y12 receptor subtypes. In oligodendrocytes, P2X7 and P2Y1 receptor subtypes have a bipartite function in respectively mediating oligodendrocyte destruction and protection. Purine receptors mediate glial pathology, with prominent roles in ischemia, neuroinflammation, Multiple Scelerosis, neuropathic pain and traumatic injury. Notably, glial ATP signalling may be altered with ageing and is implicated in impaired myelination and immunity in Alzheimer's disease. Hence, glial purine receptors provide potential therapeutic targets in multiple neuropathologies, but the 'Jeckyll and Hyde' nature of purine signalling underscores the importance of further research and a comprehensive understanding of the roles of the different purine receptors in mediating tissue damage and repair. PMID- 27400973 TI - Do Adult Phenotypes Reflect Selection on Juvenile Performance? A Comparative Study on Performance and Morphology in Lizards. AB - When competing for food or other resources, or when confronted with predators, young animals may be at a disadvantage relative to adults because of their smaller size. Additionally, the ongoing differentiation and growth of tissues may constrain performance during early ontogenetic stages. However, juveniles must feed before they can become reproductively active adults and as such the adult phenotype may be the result of an ontogenetic filter imposing selection on juvenile phenotype and performance. Here we present ontogenetic data on head morphology and bite force for different lizard species. We test whether adults reflect selection on juveniles by comparing slopes of growth trajectories before and after sexual maturity in males and females and by examining the variance in head morphology and bite force in juveniles versus adults. Finally, we also present the first results of a selection study where animals were measured, marked and released, and recaptured the subsequent year to test whether head morphology and bite force impact survival. PMID- 27400974 TI - Here We Are, But Where Do We Go? A Systematic Review of Crustacean Transcriptomic Studies from 2014-2015. AB - Despite their economic, ecological, and experimental importance, genomic resources remain scarce for crustaceans. In lieu of genomes, many researchers have taken advantage of technological advancements to instead sequence and assemble crustacean transcriptomes de novo However, there is little consensus on what standard operating procedures are, or should be, for the field. Here, we systematically reviewed 53 studies published during 2014-2015 that utilized transcriptomic resources from this taxonomic group in an effort to identify commonalities as well as potential weaknesses that have applicability beyond just crustaceans. In general, these studies utilized RNA-Seq data, both novel and publicly available, to characterize transcriptomes and/or identify differentially expressed genes (DEGs) between treatments. Although the software suite Trinity was popular in assembly pipelines and other programs were also commonly employed, many studies failed to report crucial details regarding bioinformatic methodologies, including read mappers and the utilized parameters in identifying and characterizing DEGs. Annotation percentages for assembled transcriptomic contigs were low, averaging 32% overall. While other metrics, such as numbers of contigs and DEGs reported, correlated with the number of sequence reads utilized per sample, these did reach apparent saturation with increasing sequencing depth. Most disturbingly, a number of studies (55%) reported DEGs based on non replicated experimental designs and single biological replicates for each treatment. Given this, we suggest future RNA-Seq experiments targeting transcriptome characterization conduct deeper (i.e., 50-100 M reads) sequencing while those examining differential expression instead focus more on increased biological replicates at shallower (i.e., ~10-20 M reads/sample) sequencing depths. Moreover, the community must avoid submitting for review, or accepting for publication, non-replicated differential expression studies. Finally, mining the ever growing publicly available transcriptomic data from crustaceans will allow future studies to focus on hypothesis-driven research instead of continuing to simply characterize transcriptomes. As an example of this, we utilized neurotoxin sequences from the recently described remipede venom gland transcriptome in conjunction with publicly available crustacean transcriptomic data to derive preliminary results and hypotheses regarding the evolution of venom in crustaceans. PMID- 27400975 TI - Evolutionary Conflict Between Maternal and Paternal Interests: Integration with Evolutionary Endocrinology. AB - Conflict between mates, as well as conflict between parents and offspring are due to divergent evolutionary interests of the interacting individuals. Hormone systems provide genetically based proximate mechanisms for mediating phenotypic adaptation and maladaptation characteristic of evolutionary conflict between individuals. Testosterone (T) is among the most commonly studied hormones in evolutionary biology, and as such, its role in shaping sexually dimorphic behaviors and physiology is relatively well understood, but its role in evolutionary conflict is not as clear. In this review, we outline the genomic conflicts arising within the family unit, and incorporate multiple lines of evidence from the bank vole (Myodes glareolus) system to outline how T impacts traits associated with reproduction and survival, resulting in a sexually antagonistic genetic trade-off in fitness. A major prediction arising from this work is that lower T is favored in females, whereas the optimal T level in males fluctuates in relation to social and ecological factors. We additionally discuss future directions to further integrate endocrinology into the study of sexual and parent-offspring conflicts. PMID- 27400976 TI - Can a Network Approach Resolve How Adaptive vs Nonadaptive Plasticity Impacts Evolutionary Trajectories? AB - Theoretical and empirical work has described a range of scenarios in which plasticity may shape adaptation to a novel environment. For example, recent studies have implicated a role for both adaptive and non-adaptive plasticity in facilitating adaptive evolution, yet we lack a broad mechanistic framework to predict under what conditions each scenario is likely to dominate evolutionary processes. We propose that such a framework requires understanding how transcriptional, protein, and developmental networks change in response to different rearing environments across evolutionary time scales. Our central argument is that these hierarchical networks generate and maintain phenotypic variation in populations, both by buffering organisms from developmental noise and mutational inputs and by exhibiting flexible responses to environmental cues. These network properties in turn lead to predictions about how plasticity should influence adaptive evolution. Because buffering mechanisms allow the build-up of cryptic genetic variation (i.e., genetic variation without phenotypic consequences), the initial response of individuals colonizing novel environments should be a release of genetic and phenotypic variation that selection acts upon; some of which is adaptive and some of which is not. Thus, in the early stages of adaptation, strong selection against maladaptive phenotypes should result in rapid evolution acting on standing cryptic variation. However, over longer time scales, evolutionary change should largely be compensatory, to rebuild robust developmental processes and promote integrated phenotypes. We argue that considering how hierarchical networks respond over developmental and evolutionary time encompasses a more mechanistic understanding of the genotype-phenotype map, and will result in a more predictive framework for understanding the role of plasticity in adaptive evolution. PMID- 27400977 TI - Parasite Rates of Discovery, Global Species Richness and Host Specificity. AB - If every metazoan species has at least one host-specific parasite, as several local scale studies have suggested, then half of all species could be parasites. However, host specificity varies significantly depending on host phylogeny, body size, habitat, and geographic distribution. The best studied hosts tend to be vertebrates, larger animals, and/or widespread, and thus have a higher number of parasites and host-specific parasites. Thus, host specificity for these well known taxa cannot be simply extrapolated to other taxa, notably invertebrates, small sized, and more endemic species, which comprise the major portion of yet to be discovered species. At present, parasites of animals comprise about 5% of named species. This article analyzed the rate of description of several largely parasitic taxa within crustaceans (copepods, amphipods, isopods, pentastomids, cirripeds), marine helminths (nematodes, acanthocephalans, flukes), gastropod molluscs, insects (ticks, fleas, biting flies, strepispterans), and microsporidia. The period of highest discovery has been most recent for the marine helminths and microsporids. The number of people describing parasites has been increasing since the 1960s, as it has for all other taxa. However, the number of species being described per decade relative to the number of authors has been decreasing except for the helminths. The results indicate that more than half of all parasites have been described, and two-thirds of host taxa, although the proportion varies between taxa. It is highly unlikely that the number of named species of parasites will ever approach that of their hosts. This contrast between the proportion that parasites comprise of local and global faunas suggests that parasites are less host specific and more widespread than local scale studies suggest. PMID- 27400978 TI - Developmental Transcriptomics of the Hawaiian Anchialine Shrimp Halocaridina rubra Holthuis, 1963 (Crustacea: Atyidae). AB - Many crustacean species progress through a series of metamorphoses during the developmental transition from embryo to adult. The molecular genetic basis of this transition, however, is not well characterized for a large number of crustaceans. Here, we employ multiple RNA-Seq methodologies to identify differentially expressed genes (DEGs) between "early" (i.e., Z1 - Z2) as well as "late" (i.e., Z3 - Z4) larval and adult developmental stages of Halocaridina rubra Holthuis (1963), an atyid shrimp endemic to the environmentally variable anchialine ecosystem of the Hawaiian Islands. Given the differences in salinity tolerance (narrow vs. wide range), energy acquisition (maternal yolk-bearing vs. microphagous grazing), and behavior (positively phototactic vs. not) between larvae and adults, respectively, of this species, we hypothesized the recovery of numerous DEGs belonging to functional categories relating to these characteristics. Consistent with this and regardless of methodology, hundreds of DEGs were identified, including upregulation of opsins and other light/stimulus detection genes and downregulation of genes related to ion transport, digestion, and reproduction in larvae relative to adults. Furthermore, isoform-switching, which has been largely unexplored in crustacean development, appears to be pervasive between H. rubra larvae and adults, especially among structural and oxygen-transport genes. Finally, by comparing RNA-Seq methodologies, we provide recommendations for future crustacean transcriptomic studies, including a demonstration of the pitfalls associated with identifying DEGs from single replicate samples as well as the utility of leveraging "prepackaged" bioinformatics pipelines. PMID- 27400980 TI - Phosphorylation of Bni4 by MAP kinases contributes to septum assembly during yeast cytokinesis. AB - Previous work has shown that the synthetic lethality of the slt2Deltarim101Delta mutant results from a combination of factors, including improper functioning of the septum assembly machinery. Here, we identify new multicopy suppressors of this lethality including Kss1, Pcl1 and Sph1, none of which seems to be linked to the upregulation of chitin synthesis. Characterization of the suppression mediated by Kss1 showed that it is independent of the transcriptional response of the CWI signaling response, but efficiently restores the Bni4 localization defects produced by the absence of Slt2. Accordingly, Bni4 interacts physically with both kinases, and its levels of phosphorylation are reduced in the slt2Delta mutant but increased after Kss1 overexpression. Using an assay based on hypersensitive cells of the cdc10-11 mutant, we have pinpointed several MAP kinase phosphorylatable residues required for Bni4 function. Our results, together with a genetic correlation analysis, strongly support a functional model linking Slt2 MAP kinase and Pcl1, a Pho85 cyclin-dependent kinase, in septum assembly through Bni4. This model, based on the coordinated phosphorylation of Bni4 by both kinases, would be able to integrate cellular signals rapidly to maintain cell integrity during cytokinesis. PMID- 27400979 TI - The Use of Social Media for Health Promotion in Hispanic Populations: A Scoping Systematic Review. AB - BACKGROUND: The Internet is an increasingly popular platform for public health interventions due to its distinct ability to communicate with, engage, and educate communities. Given the widespread use of the Internet, these interventions could be a means of equalizing access to information to address health disparities in minority populations, such as Hispanics. Hispanics are disproportionately affected by poor health outcomes, including obesity, diabetes, and human immunodeficiency virus/acquired immune deficiency syndrome. Although underserved and underrepresented, Hispanics are among the leading users of social media in the United States. Previous reviews have examined the use of social media in public health efforts, but, to our knowledge, none have focused on the Hispanic population. OBJECTIVE: To conduct a scoping systematic review of the published literature to capture the ways social media has been used in health interventions aimed at Hispanic populations and identify gaps in existing knowledge to provide recommendations for future research. METHODS: We performed a systematic review of the literature related to social media, public health, and Hispanics using the PubMed, PsycINFO, and EMBASE databases to locate peer reviewed studies published between January 1, 2010, and December 31, 2015. Each article was reviewed for the following inclusion criteria: social media as a main component of study methodology or content; public health topic; majority Hispanic/Latino study population; English or Spanish language; and original research study. Relevant data were extracted from articles meeting inclusion criteria including publication year, location, study design, social media platform, use of social media, target population, and public health topic. RESULTS: Of the 267 articles retrieved, a total of 27 unique articles met inclusion criteria. All were published in 2012 or later. The most common study design was a cross-sectional survey, which was featured in 10 of the 27 (37%) articles. All articles used social media for at least one of the following three purposes: recruiting study participants (14 of 27, 52%), promoting health education (12 of 27, 44%), and/or describing social media users (12 of 27, 44%). All but one article used multiple social media platforms, though Facebook was by far the most popular appearing in 24 of the 27 (89%). A diverse array of Hispanic populations was targeted, and health topics featured. Of these, the most highly represented were articles on sexual health directed toward Latino men who have sex with men (12 of 27, 44%). Healthy eating and active living received the second greatest focus (4 of 27, 15%). CONCLUSIONS: Social media offers a potential accessible venue for health interventions aimed at Hispanics, a group at disproportionate risk for poor health outcomes. To date, most publications are descriptive in nature, with few indicating specific interventions and associated outcomes to improve health. PMID- 27400981 TI - alpha,beta-Dicarbonyl reduction is mediated by the Saccharomyces Old Yellow Enzyme. AB - The undesirable flavor compounds diacetyl and 2,3-pentanedione are vicinal diketones (VDKs) formed by extracellular oxidative decarboxylation of intermediate metabolites of the isoleucine, leucine and valine (ILV) biosynthetic pathway. These VDKs are taken up by Saccharomyces and enzymatically converted to acetoin and 3-hydroxy-2-pentanone, respectively. Purification of a highly enriched diacetyl reductase fraction from Saccharomyces cerevisiae in conjunction with mass spectrometry identified Old Yellow Enzyme (Oye) as an enzyme capable of catalyzing VDK reduction. Kinetic analysis of recombinant Oye1p, Oye2p and Oye3p isoforms confirmed that all three isoforms reduced diacetyl and 2,3-pentanedione in an NADPH-dependent reaction. Transcriptomic analysis of S. cerevisiae (ale) and S. pastorianus (lager) yeast during industrial fermentations showed that the transcripts for OYE1, OYE2, arabinose dehydrogenase (ARA1), alpha-acetolactate synthase (ILV2) and alpha-acetohydroxyacid reductoisomerase (ILV5) were differentially regulated in a manner that correlated with changes in extracellular levels of VDKs. These studies provide insights into the mechanism for reducing VDKs and decreasing maturation times of beer which are of commercial importance. PMID- 27400982 TI - NHS failed to commission mental health services properly at Yarl's Wood. PMID- 27400984 TI - Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. AB - Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients. PMID- 27400983 TI - Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study. AB - BACKGROUND: Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics. METHODS: The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models. RESULTS: Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53-1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1-4 years (RR = 0.59; 95 % CI = 0.45-0.77) and 5-9 years (RR = 0.73; 95 % CI = 0.56-0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies. CONCLUSION: Our findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed. PMID- 27400985 TI - Costs and economic consequences of a help-at-home scheme for older people in England. AB - Solutions to support older people to live independently and reduce the cost of an ageing population are high on the political agenda of most developed countries. Help-at-home schemes offer a mix of community support with the aim to address a range of well-being needs. However, not much is currently known about the costs, outcomes and economic consequences of such schemes. Understanding their impact on individuals' well-being and the economic consequences for local and central government can contribute to decisions about sustainable long-term care financing. This article presents results from a mixed-methods study of a voluntary sector-provided help-at-home scheme in England for people of 55 years and older. The study followed a participatory approach, which involved staff and volunteers. Data were collected during 2012 and 2013. Social care-related quality of life was measured with the Adult Social Care Outcomes Toolkit for 24 service users (59% response rate) when they started using the scheme and 4-6 months later. A customised questionnaire that captured resource use and well-being information was sent to 1064 service users (63% response rate). The same tool was used in assessment with service users who started using the scheme between November 2012 and April 2013 (100% response rate). Costs of the scheme were established from local budget and activity data. The scheme was likely to achieve a mean net benefit of L1568 per person from a local government and National Health Service (NHS) perspective and L3766 from the perspective of the individual. An expenditure of L2851 per person accrued to central government for the additional redistribution of benefit payments to older people. This article highlights the potential contribution of voluntary sector-run help-at-home schemes to an affordable welfare system for ageing societies. PMID- 27400986 TI - Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells. AB - In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP). Both the inhibition of early stage autophagy flux and lysosomal cathepsins did not improve cell viability. The antioxidant, n-acetylcysteine, and the iron chelator, deferoxamine, failed to restore the lysosomal integrity indicating that PRE-induced LMP is independent of oxidative stress. This was corroborated with the absence of enhanced ROS production in PRE-treated cells. Chelation of both intracellular calcium and zinc promotes PRE-induced LMP. Geranylgeranylacetone, an inducer of Hsp70 expression, also had no significant protective effect on PRE induced LMP. Moreover, we found that PRE induces endoplasmic reticulum (ER) stress and mitochondrial membrane depolarization in MCF-7 cells. The ER stress inhibitor, 4-PBA, did not restore the mitochondrial membrane integrity, whereas cathepsin inhibitors demonstrated significant protective effects. Collectively, our results suggest that PRE induces an autophagic block, LMP, ER stress, and mitochondrial dysfunction in MCF-7 cells. However, further studies are clearly warranted to explore the exact mechanism behind the anticancer activity of PRE in MCF-7 human breast cancer cells. PMID- 27400987 TI - Population attributable fraction of Esophageal squamous cell carcinoma due to smoking and alcohol in Uganda. AB - BACKGROUND: Despite the high rates and regional variation of esophageal squamous cell carcinoma (ESCC) in East Africa, the contributions of smoking and alcohol to the ESCC burden in the general population are unknown. METHODS: We conducted a case-control study of patients presenting for upper gastrointestinal endoscopic examination at Mbarara Regional Referral Hospital, Uganda. Sociodemographic data including smoking and alcohol intake were collected prior to endoscopy. Cases were those with histological diagnosis of ESCC and controls were participants with normal endoscopic examination and gastritis/duodentitis or normal histology. We used odds ratios associated with ESCC risk to determine the population attributable fractions for smoking, alcohol use, and a combination of smoking and alcohol use among adults aged 30 years or greater who underwent upper gastrointestinal endoscopy. RESULTS: Our study consisted of 67 cases and 142 controls. Median age was 51 years (IQR 40-64); and participants were predominantly male (59 %). Dysphagia and/or odynophagia as indications for endoscopy were significantly more in cases compared to controls (72 % vs 6 %, p < 0.0001). Male gender and increasing age were statistically associated with ESCC. In the unadjusted models, the population attributable fraction of ESCC due to male gender was 55 %, female gender - 49 %, smoking 20 %, alcohol 9 % and a combination of alcohol & smoking 15 %. After adjusting for gender and age, the population attributable fraction of ESCC due to smoking, alcohol intake and a combination of alcohol & smoking were 16, 10, and 13 % respectively. CONCLUSION: In this population, 13 % of esophageal squamous cell carcinoma cases would be avoided if smoking and alcohol use were discontinued. These results suggest that other important risk factors for ESCC in southwestern Uganda remain unknown. PMID- 27400989 TI - Nucleic acid polymers: Broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection. AB - Antiviral polymers are a well-studied class of broad spectrum viral attachment/entry inhibitors whose activity increases with polymer length and with increased amphipathic (hydrophobic) character. The newest members of this class of compounds are nucleic acid polymers whose activity is derived from the sequence independent properties of phosphorothioated oligonucleotides as amphipathic polymers. Although the antiviral mechanisms and broad spectrum antiviral activity of nucleic acid polymers mirror the functionality of other members of this class, they exert in addition a unique post entry activity in hepatitis B infection which inhibits the release of HBsAg from infected hepatocytes. This review provides a general overview of the antiviral polymer class with a focus on nucleic acid polymers and their development as therapeutic agents for the treatment of hepatitis B/hepatitis D. This article forms part of a symposium in Antiviral Research on ''An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.''. PMID- 27400988 TI - Use of Cupriavidus basilensis-aided bioabatement to enhance fermentation of acid pretreated biomass hydrolysates by Clostridium beijerinckii. AB - Lignocellulose-derived microbial inhibitors (LDMICs) prevent efficient fermentation of Miscanthus giganteus (MG) hydrolysates to fuels and chemicals. To address this problem, we explored detoxification of pretreated MG biomass by Cupriavidus basilensis ATCC((r))BAA-699 prior to enzymatic saccharification. We document three key findings from our test of this strategy to alleviate LDMIC mediated toxicity on Clostridium beijerinckii NCIMB 8052 during fermentation of MG hydrolysates. First, we demonstrate that growth of C. basilensis is possible on furfural, 5-hydroxymethyfurfural, cinnamaldehyde, 4-hydroxybenzaldehyde, syringaldehyde, vanillin, and ferulic, p-coumaric, syringic and vanillic acid, as sole carbon sources. Second, we report that C. basilensis detoxified and metabolized ~98 % LDMICs present in dilute acid-pretreated MG hydrolysates. Last, this bioabatement resulted in significant payoffs during acetone-butanol-ethanol (ABE) fermentation by C. beijerinckii: 70, 50 and 73 % improvement in ABE concentration, yield and productivity, respectively. Together, our results show that biological detoxification of acid-pretreated MG hydrolysates prior to fermentation is feasible and beneficial. PMID- 27400990 TI - Rift Valley fever virus: Unanswered questions. AB - This mosquito-borne pathogen of humans and animals respects no international or geographic boundaries. It is currently found in parts of Africa and the Arabian Peninsula where periodic outbreaks of severe and fatal disease occur, and threatens to spread into other geographic regions. In recent years, modern molecular techniques have led to many breakthroughs deepening our understanding of the mechanisms of RVFV virulence, phylogenetics, and the creation of several next-generation vaccine candidates. Despite tremendous progress in these areas, other challenges remain in RVF disease pathogenesis, the virus life-cycle, and outbreak response preparedness that deserve our attention. Here we discuss and highlight ten key knowledge gaps and challenges in RVFV research. Answers to these key questions may lead to the development of new effective therapeutics and enhanced control strategies for this serious human and veterinary health threat. PMID- 27400991 TI - Awake emergency endotracheal intubation using sheath-assisted technique for patients having malignant tracheal stenosis under fluoroscopy guidance: a retrospective study. AB - Background For patients having a severe larynx or tracheal stenosis, emergency endotracheal intubation (EEI) may be needed due to respiratory failure. Purpose To evaluate the feasibility and effectiveness of awake EEI using a fluoroscopy guided sheath-assisted technique for adult patients having a malignant tracheal stenosis. Material and Methods From October 2009 to May 2015, 219 patients having a malignant tracheal stenosis causing dyspnea or asphyxia required EEI. Of these, 32 patients who experienced intubation difficulties or failure were included in this study. Data on the technical success, procedure time, complications, and clinical outcome were collected. The pulse oxygen saturation (SpO2) and Hugh Jones classification were used to evaluate the respiratory function before and after EEI. Results Awake fluoroscopy-guided EEI was technically successful in 15 +/- 4 min and acute dyspnea was resolved in all patients. The SpO2 and Hugh-Jones classification increased after EEI ( P < 0.05). Subsequent treatments included tracheal stents (n = 15), surgical resection (n = 10), and palliative tracheotomy (n = 7), which were performed within 72 h after EEI. Conclusion Awake EEI using a sheath-assisted technique for adult patients having a malignant tracheal stenosis is a safe and effective procedure. PMID- 27400992 TI - The entry of cucumber mosaic virus into cucumber xylem is facilitated by co infection with zucchini yellow mosaic virus. AB - We investigated the synergistic effects of co-infection by zucchini yellow mosaic virus (ZYMV) and cucumber mosaic virus (CMV) on viral distribution in the vascular tissues of cucumber. Immunohistochemical observations indicated that ZYMV was present in both the phloem and xylem tissues. ZYMV-RNA was detected in both the xylem wash and guttation fluid of ZYMV-inoculated cucumber. Steam treatment at a stem internode indicated that ZYMV enters the xylem vessels and moves through them but does not cause systemic infection in the plant. CMV distribution in singly infected cucumbers was restricted to phloem tissue. By contrast, CMV was detected in the xylem tissue of cotyledons in plants co infected with CMV and ZYMV. Although both ZYMV-RNA and CMV-RNA were detected in the xylem wash and upper internodes of steam-treated, co-infected cucumbers grown at 24 degrees C, neither virus was detected in the upper leaves using an ELISA assay. Genetically modified CMV harboring the ZYMV HC-Pro gene was distributed in the xylem and phloem tissues of singly inoculated cucumber cotyledons. These results indicate that the ZYMV HC-Pro gene facilitates CMV entry into the xylem vessels of co-infected cucumbers. PMID- 27400993 TI - A naturally truncated NS1 protein of influenza A virus impairs its interferon antagonizing activity and thereby confers attenuation in vitro. AB - The non-structural protein of influenza A virus (NS1A protein) is a multifunctional protein that antagonizes host antiviral responses and contributes to efficient viral replication during infection. However, most of its functions have been elucidated by generating recombinant viruses expressing mutated NS1 proteins that do not exist in nature. Recently, the novel H3N8 A/Equine/Kyonggi/SA1/2011 (KG11) influenza virus was isolated in Korea from horses showing respiratory disease symptoms. KG11 virus contains a naturally truncated NS gene segment with the truncation in the NS1A coding region, resulting in truncation of the effector domain of the NS1A protein. Using this KG11 virus, we investigated the role of truncated NS1A protein in the virus life cycle and its effect on host immune responses were compared to the A/Equine/Miami/1/1963 H3N8 (MA63) virus, which encodes a full-length NS1A protein. The replication of KG11 virus was attenuated by 2 logs in multiple-cycle growth, and its plaque size was significantly smaller than that of the MA63 virus. To understand the attenuation of KG11 virus, we evaluated the level of activation in Akt and interferon regulatory factor 3 (IRF-3) pathways and measured the induction of downstream genes. Our results showed that the activation of Akt was reduced, whereas phosphorylation of IRF-3 was increased in cells infected with KG11 virus when compared to MA63-virus-infected cells. We also determined that the expression of antiviral and pro-inflammatory genes was significantly increased. Taken together, these results revealed that the KG11 virus expressing the naturally truncated NS1A protein impairs the inhibition of host antiviral responses, thereby resulting in the attenuation of viral replication. PMID- 27400994 TI - Clinical and molecular investigation of Buschke-Fischer-Brauer in consanguineous Tunisian families. AB - BACKGROUND: Punctate palmoplantar keratoderma type I (PPPK-BFB), also called Buschke-Fischer-Brauer disease (MIM 148600) is a rare autosomal dominant disorder of keratinization, characterized by multiple hyperkeratotic lesions on the palms and soles. Recently, PPPK-BFB has been shown to be associated with mutations in the AAGAB gene in several families of European, African, Canadian and Asian origins. OBJECTIVE: To characterize the clinical and genetic features of PPPK-BFB in a broad group of Tunisian patients. METHODS: Epidemiological and clinical data were collected from 18 PPPK-BFB patients belonging to eight Tunisian families. We carried out mutational and structural analysis for families not previously investigated. RESULTS: Sequencing of the remaining families identified a total of three different mutations in AAGAB gene: one founder mutation (c.348_349delAG, p.R116Sfs*1) specific to the inbred Tunisian population, one recurrent mutation and (c.370C>T, p.R124*) one novel variant (c.430C>G, p.E144K). This novel mutation, involving a conserved amino acid, is predicted to be probably damaging to the p34 protein function. Assessment of the phenotypic presentation of this group of Tunisian patients was marked by variable severity and varying age at onset with a possible presence of anticipation noted in five out of eight families (62.5%). There is no apparent genotype-phenotype correlation. Despite the high degree of inbreeding, no homozygous individuals for AAGAB mutations were observed. Homozygous carriers in AAGAB gene are likely non-viable. CONCLUSION: This study contributes to further characterize PPPK-BFB in consanguineous families and to extend the mutational spectrum of AAGAB gene in the Tunisian population. PMID- 27400995 TI - The reliability of criterion shifting in recognition memory is task dependent. AB - We explored 2 research questions: whether criterion shifts within different recognition tasks are reliable across testing sessions and whether such shifts correlate across the different tasks. In Experiment 1, we established consistent group-level criterion shifting based on expected strength of target items in the test. False-alarm rates were higher when expected strength was weak as opposed to strong, even when expected strength cues were unblocked at test. Test-retest reliabilities in this strength-cuing environment were good. In Experiment 2, we manipulated either the probability (high or low) or expected memory strength (strong or weak) of target items and had people perform both tasks on each of 2 days of testing. Varying the probability of target items consistently produced criterion shifts, as did manipulating target memory strength. Regarding individual differences, shifting in a given test context predicted shifting on a second day in that same test context. However, one's tendency to shift a decision criterion on 1 type of test context did not predict one's tendency to do so in the other. The extent to which people shifted their decision criterion in recognition memory testing was largely dependent on the type of test. PMID- 27400996 TI - Mitochondrial Flashes: Dump Superoxide and Dance with Protons Now. AB - Transient changes in the physiology of individual mitochondria have recently drawn much interest. The use of a circular permuted yellow fluorescent protein (cpYFP) to monitor mitochondrial flashes and their interpretation as superoxide bursts has added confusion, however. Reviewing mitochondrial flashes in this Forum, Wang et al. again deem cpYFP to be a specific and reversible superoxide indicator, dismissing evidence that purified cpYFP is insensitive to superoxide. This interpretation lacks reproducible evidence and conflicts with the parsimony principle. We offer a constructive, transparent pathway to reach definitive clarification of contradictory reports. Antioxid. Redox Signal. 25, 550-551. PMID- 27400998 TI - Evaluation of the Orbitrap Mass Spectrometer for the Molecular Fingerprinting Analysis of Natural Dissolved Organic Matter. AB - We investigated the application of the LTQ-Orbitrap mass spectrometer (LTQ-Velos Pro, Thermo Fisher) for resolving complex mixtures of natural aquatic dissolved organic matter (DOM) and compared this technique to the more established state-of the-art technique, Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS, Bruker Daltonics), in terms of the distribution of molecular masses detected and the reproducibility of the results collected. The Orbitrap was capable of excellent reproducibility: Bray-Curtis dissimilarity between duplicate measurements was 2.85 +/- 0.42% (mean +/- standard deviation). The Orbitrap was also capable of the detection of most major ionizable organic molecules in typical aquatic mixtures, with the exception of most sulfur and phosphorus containing masses. This result signifies that the Orbitrap is an appropriate technique for the investigation of very subtle biogeochemical processing of bulk DOM. The lower costs (purchase and maintenance) and wider availability of Orbitrap mass spectrometers in university departments means that the tools necessary for research into DOM processing at the molecular level should be accessible to a much wider group of scientists than before. The main disadvantage of the technique is that substantially fewer molecular formulas can be resolved from a complex mixture (roughly one third as many), meaning some loss of information. In balance, most biogeochemical studies that aim at molecularly fingerprinting the source of natural DOM could be satisfactorily carried out with Orbitrap mass spectrometry. For more targeted metabolomic studies where individual compounds are traced through natural systems, FTICR-MS remains advantageous. PMID- 27400997 TI - Effect of high-dose vitamin D supplementation on cardiometabolic risk factors in subjects with metabolic syndrome: a randomized controlled double-blind clinical trial. AB - PURPOSE: The evidence in support of the effect of vitamin D deficiency on cardiovascular diseases is inconsistent. The objective of this randomized, controlled, double-blind study was to assess the effect of high-dose vitamin D supplementation on cardiometabolic risk factors in subjects with metabolic syndrome. METHODS: Eighty subjects were randomized to receive 50,000 IU vitamin D or matching placebo weekly for 16 weeks. Fasting blood sugar, homeostasis model assessment of insulin resistance, insulin sensitivity (Quicki), serum lipid profiles (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride (TG) and total cholesterol), anthropometric factors and blood pressure were assessed before and after intervention. Dietary intake and sun exposure were also determined. The trial was registered at http://www.irct.ir (code: IRCT201409033140N14). RESULTS: Participants were 40.49 +/- 5.04 years and 49 % male. All of the intervention group and 97 % of placebo group were vitamin D deficient or insufficient (25-hydroxyvitamin D <75 nmol/L). After intervention, serum 25(OH)D concentration was increased by 61.93 nmol/L in intervention group, while it was decreased in placebo group (p < 0.001). There was a significant change in TG concentration after 4 months (p < 0.001). Other metabolic or anthropometric factors did not change significantly (p = 0.05). CONCLUSION: Supplementation with high-dose vitamin D for 4 months improved vitamin D status and decreased TG levels in subjects with metabolic syndrome. However, it did not have any beneficial effects on other cardiometabolic risk factors; this might be due to the inadequate vitamin D status attained in this study which was conducted in a severely deficient region. PMID- 27400999 TI - The impact of parkinson's disease on the cortical mechanisms that support auditory-motor integration for voice control. AB - Several studies have shown sensorimotor deficits in speech processing in individuals with idiopathic Parkinson's disease (PD). The underlying neural mechanisms, however, remain poorly understood. In the present event-related potential (ERP) study, 18 individuals with PD and 18 healthy controls were exposed to frequency-altered feedback (FAF) while producing a sustained vowel and listening to the playback of their own voice. Behavioral results revealed that individuals with PD produced significantly larger vocal compensation for pitch feedback errors than healthy controls, and exhibited a significant positive correlation between the magnitude of their vocal responses and the variability of their unaltered vocal pitch. At the cortical level, larger P2 responses were observed for individuals with PD compared with healthy controls during active vocalization due to left-lateralized enhanced activity in the superior and inferior frontal gyrus, premotor cortex, inferior parietal lobule, and superior temporal gyrus. These two groups did not differ, however, when they passively listened to the playback of their own voice. Individuals with PD also exhibited larger P2 responses during active vocalization when compared with passive listening due to enhanced activity in the inferior frontal gyrus, precental gyrus, postcentral gyrus, and middle temporal gyrus. This enhancement effect, however, was not observed for healthy controls. These findings provide neural evidence for the abnormal auditory-vocal integration for voice control in individuals with PD, which may be caused by their deficits in the detection and correction of errors in voice auditory feedback. Hum Brain Mapp 37:4248-4261, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27401001 TI - From Theory-Inspired to Theory-Based Interventions: A Protocol for Developing and Testing a Methodology for Linking Behaviour Change Techniques to Theoretical Mechanisms of Action. AB - Background: Understanding links between behaviour change techniques (BCTs) and mechanisms of action (the processes through which they affect behaviour) helps inform the systematic development of behaviour change interventions. Purpose: This research aims to develop and test a methodology for linking BCTs to their mechanisms of action. Methods: Study 1 (published explicit links): Hypothesised links between 93 BCTs (from the 93-item BCT taxonomy, BCTTv1) and mechanisms of action will be identified from published interventions and their frequency, explicitness and precision documented. Study 2 (expert-agreed explicit links): Behaviour change experts will identify links between 61 BCTs and 26 mechanisms of action in a formal consensus study. Study 3 (integrated matrix of explicit links): Agreement between studies 1 and 2 will be evaluated and a new group of experts will discuss discrepancies. An integrated matrix of BCT-mechanism of action links, annotated to indicate strength of evidence, will be generated. Study 4 (published implicit links): To determine whether groups of co-occurring BCTs can be linked to theories, we will identify groups of BCTs that are used together from the study 1 literature. A consensus exercise will be used to rate strength of links between groups of BCT and theories. Conclusions: A formal methodology for linking BCTs to their hypothesised mechanisms of action can contribute to the development and evaluation of behaviour change interventions. This research is a step towards developing a behaviour change 'ontology', specifying relations between BCTs, mechanisms of action, modes of delivery, populations, settings and types of behaviour. PMID- 27401000 TI - Blood Pressure and Fibrinogen Responses to Mental Stress as Predictors of Incident Hypertension over an 8-Year Period. AB - BACKGROUND: Heightened blood pressure (BP) responses to mental stress predict raised BP levels over subsequent years, but evidence for associations with incident hypertension is limited, and the significance of inflammatory responses is uncertain. PURPOSE: We investigated the relationship between BP and plasma fibrinogen responses to stress and incident hypertension over an average 8-year follow-up. METHOD: Participants were 636 men and women (mean age 59.1 years) from the Whitehall II epidemiological cohort with no history of cardiovascular disease and hypertension. They performed standardized behavioral tasks (color/word conflict and mirror tracing), and hypertension was defined by clinic measures and medication status. RESULTS: Of participants in the highest systolic BP reactivity tertile, 29.3 % became hypertensive over the follow-up period compared with 16.5 % of those in the lowest tertile, with an odds ratio of 2.02 (95 % CI 1.17-3.88, p = 0.012) after adjustment for age, sex, grade of employment, body mass index, smoking, alcohol consumption, physical activity, follow-up time, subjective stress response, perceived task difficulty, perceived task engagement, and baseline BP. Similar associations were observed for diastolic BP reactivity (odds ratio 2.05, 95 % CI 1.23-3.40, p = 0.006) and for impaired systolic BP post stress recovery (odds ratio 2.06, 95 % CI 1.19-3.57, p = 0.010). Fibrinogen reactions to tasks also predicted future hypertension in women (odds ratio 2.64, 95 % CI 1.11-6.30, p = 0.029) but not men. CONCLUSIONS: These data suggest that heightened cardiovascular and inflammatory reactivity to mental stress is associated with hypertension risk, and may be a mechanism through which psychosocial factors impact on the development of hypertension. PMID- 27401002 TI - Pediatric musculoskeletal ultrasound: age- and sex-related normal B-mode findings of the knee. AB - Musculoskeletal ultrasound (MSUS) is an important tool for evaluating disease activity, therapeutic progress, and remission status of rheumatic diseases in children. Knowledge of age-related normal findings is essential when interpreting pathological findings such as those seen in juvenile idiopathic arthritis. To evaluate normal findings of the knee joint, we recorded age-related stages of musculoskeletal development in the knee of 435 healthy children between 1 and 18 years of age using high-resolution B-mode MSUS. We determined approximate age- and sex-related norms for the suprapatellar recess size, ossified patella size, and distal femoral intercondylar cartilage thickness. In almost all age-groups, over 64 % of children had visible fluid accumulation in the suprapatellar recess. Significant correlations were found between chronological age and the suprapatellar recess size and ossified patella length (p < 0.05). An age dependent decrease in intercondylar cartilage thickness of the distal femoral epiphysis was found in children between 10 and 18 years of age. High-resolution B mode MSUS is an excellent tool for assessing joint and skeletal development in children. Our reference data can be used to discriminate better between normal physiological findings and pathological abnormalities. PMID- 27401003 TI - Articulated spacer provides long-term knee improvement after two-stage reimplantation. AB - PURPOSE: The purpose of this study was to determine the long-term outcome in patients who underwent two-stage reimplantation with an articulated spacer following a chronic periprosthetic knee infection. The hypothesis was that the use of an articulated spacer provides significant improvement of clinical results and knee functionality through a long follow-up period, and therefore a durable revision TKA. METHODS: Forty-six consecutive patients (46 knees) who underwent two-stage reimplantation with an articulated spacer for a chronic periprosthetic knee infection were retrospectively analysed. An articulated cement spacer, moulded in surgery room, was implanted in all cases. Patients were followed for a median period of 12 (range 6-16) years, and no patients were lost to follow-up. Patients were assessed preoperatively and postoperatively through the IKS knee and function scores and ROM. RESULTS: Two-stage reimplantation was successful in controlling the infection in 91.3 % of patients. In the 42 patients with a successful two-stage revision, the median IKS knee and function scores were 36 (range 16-56) points and 25 (range 15-35) points, respectively, before the operation, and 76 (range 52-94) points and 70 (range 55-90) points (p < 0.001) at the last follow-up. The median ROM increased from 80 (range 60-110) degrees preoperatively to 115 (range 100-128) degrees (p < 0.01) at the last follow-up. CONCLUSIONS: Two-stage septic revision with an articulated cement spacer provided a significant long-term improvement of preoperative clinical and functional knee scores and therefore a durable revision TKA. LEVEL OF EVIDENCE: Retrospective case series, Level IV. PMID- 27401004 TI - Efficacy and safety of home-based exercises versus individualized supervised outpatient physical therapy programs after total knee arthroplasty: a systematic review and meta-analysis. AB - PURPOSE: The aim of the present study was to evaluate the efficacy and safety of non-supervised home-based exercise versus individualized and supervised programs delivered in clinic-based settings for the functional recovery immediately after discharge from a primary TKA. METHODS: Medline, Embase, Cochrane, and PEDro databases were screened, from inception to April 2015, in search for randomized clinical trials (RCT) of home-based exercise interventions versus individualized and supervised outpatient physical therapy after primary TKA. Target outcomes were: knee range of motion (ROM), patient-reported pain and function, functional performance, and safety. Risk of bias was assessed with the PEDro scale. After assessing homogeneity, data were combined using random effects meta-analysis and reported as standardized mean differences or mean differences. We set a non inferiority margin of four points in mean differences. RESULTS: The search and selection process identified 11 RCT of moderate quality and small sample sizes. ROM active extension data suitable for meta-analysis was available from seven studies with 707 patients, and ROM active flexion from nine studies with 983 patients. Most studies showed no difference between groups. Pooled differences were within the non-inferiority margin. Most meta-analyses showed significant statistical heterogeneity. CONCLUSION: Short-term improvements in physical function and knee ROM do not clearly differ between outpatient physiotherapy and home-based exercise regimes in patients after primary TKA; however, this conclusion is based on a meta-analysis with high heterogeneity. LEVEL OF EVIDENCE: I. PMID- 27401005 TI - Peroneal electromechanical delay and fatigue in patients with chronic ankle instability. AB - PURPOSE: The purpose of this study was to investigate the effect of chronic ankle instability (CAI) on electromechanical delay times (EMD) before and after fatigue. Understanding the mechanisms that contribute to CAI is essential for the development of effective rehabilitation programmes. It was hypothesized that patients with CAI will demonstrate prolonged EMD times compared to healthy subjects and that fatigue will cause greater increases in EMD times in the CAI group. METHODS: Twenty-one male volunteers participated in the study providing data on 16 ankles with CAI and 26 with no history of ankle injury. EMD was measured on an isokinetic dynamometer. Measurements were taken with the ankle in neutral (0 degrees ) and at 30 degrees of inversion. All subjects followed an isokinetic fatigue protocol until eversion torque fell below 50 % of initial torque for three consecutive repetitions. A 2 * 2 * 2 ANOVA was used to calculate the effect of ankle status (CAI vs. healthy), fatigue, angle (0 degrees vs. 30 degrees ) and their interactions on EMD. RESULTS: Fatigue caused a significant increase on EMD [non-fatigued: 122(29)ms vs. fatigue 155(54)ms; p < 0.001]. EMD times were shorter at 30 degrees of inversion compared to neutral [neutral: 145(39)ms vs. 30 degrees of inversion: 132(40)ms, p = 0.015]. An interaction effect for ankle status and angle was found (p = 0.026) with CAI ankles demonstrating longer EMD [CAI: 156(45)ms vs. healthy: 133(40)ms] in neutral but not at 30 degrees of inversion [CAI: 133(46)ms vs. 132(33)ms]. CONCLUSIONS: Patients with CAI had longer EMD times in neutral, but not when the ankle was placed in inversion. This suggests that rehabilitation programmes may be more effective when retraining occurs with the ankle in neutral position. It is likely that low EMD times prevent ankle acceleration at the beginning of the mechanism of injury, but they are less important when the ankle has already inverted at 30 degrees . Both CAI and healthy subjects demonstrated longer EMD after fatigue, emphasizing the importance of proper conditioning in the prevention of delayed peroneal response and subsequent ankle injury. Improving resistance to fatigue of the peroneals may prove to be an effective prevention tool of ankle sprain recurrence in patients with CAI. LEVEL OF EVIDENCE: III. PMID- 27401006 TI - Biomechanical and viscoelastic properties of different posterior meniscal root fixation techniques. AB - PURPOSE: The purpose of the present study was to biomechanically compare three different posterior meniscal root repair techniques. Transtibial fixation of a posterior meniscus root tear (PMRT) combined with an anterior cruciate ligament (ACL) reconstruction via one tunnel only shows similar properties in terms of cyclic loading and load to failure compared with direct anchor fixation. METHODS: Twenty-eight porcine knees were randomly assigned to 4 groups (n = 7 each): (1) native posterior meniscal root, (2) suture anchor repair, (3) refixation via a tibial ACL tunnel in combination with an interference screw fixation of the ACL graft, and (4) refixation via a tibial ACL tunnel in combination with an interference screw fixation of the ACL graft with an additional extracortical button fixation. The four groups underwent cyclic loading followed by a load-to failure testing. Construct elongation during 1000 cycles, dynamic stiffness, attenuation, maximum force during load-to-failure testing, and failure mode were recorded. RESULTS: All reconstructions showed a significant lower maximum load (p < 0.0001) compared with the native meniscal root. The elongation for the transtibial fixation via the ACL tunnel without an additional extracortical backup fixation was significantly higher compared with the suture anchor technique (p < 0.0001). The additional use of a backup fixation led to similar results compared with the anchor repair technique. CONCLUSION: The transtibial refixation of the meniscal root can be combined with an ACL reconstruction using the same tibial bone tunnel. However, an additional extracortical backup fixation is necessary. This might avoid a slippage of suture material and a failure of meniscus root fixation. PMID- 27401007 TI - Preoperative and post-operative sleep quality evaluation in rotator cuff tear patients. AB - PURPOSE: The aim of this study was to examine the potential relationship between subjective sleep quality and degree of pain in patients with rotator cuff repair. METHODS: Thirty-one patients who underwent rotator cuff repair prospectively completed the Pittsburgh Sleep Quality Index, the Western Ontario Rotator Cuff Index, and the Constant and Murley shoulder scores before surgery and at 6 months after surgery. Preoperative demographic, clinical, and radiologic parameters were also evaluated. RESULTS: The study analysed 31 patients with a median age of 61 years. There was a significant difference preoperatively versus post-operatively in terms of all PSQI global scores and subdivisions (p < 0.001). A statistically significant improvement was determined by the Western Ontario Rotator Cuff Scale and the Constant and Murley shoulder scores (p ? 0.001). CONCLUSION: Sleep disorders are commonly seen in patients with rotator cuff tear, and after repair, there is an increase in the quality of sleep with a parallel improvement in shoulder functions. However, no statistically significant correlation was determined between arthroscopic procedures and the size of the tear and sleep quality. It is suggested that rotator cuff tear repair improves the quality of sleep and the quality of life. LEVEL OF EVIDENCE: IV. PMID- 27401008 TI - Inhibition of Runx2 signaling by TNF-alpha in ST2 murine bone marrow stromal cells undergoing osteogenic differentiation. AB - Tumor necrosis factor-alpha (TNF-alpha) inhibits osteogenic differentiation of murine bone marrow stromal cells, and transcription factor Runx2 serves as an essential regulation target in the process. The underlying mechanism may involve the regulation of Runx2 expression and the Runx2 activity in downstream gene transcription, which has not been fully elucidated. In this study, ST2 murine bone marrow-derived stromal cells were treated with bone morphogenetic protein-2 (BMP-2) and/or TNF-alpha in osteogenic medium, and the expression of Runx2 was estimated. Cells were transfected with Runx2, p65, inhibitor of kappaBalpha (IkappaBalpha), 9.0 kb bone sialoprotein (BSP) promoter-luciferase or osteoblast specific cis-acting element 2 (OSE2)-luciferase reporter vectors, and then real time-PCR and dual luciferase analysis were used to investigate the effect of TNF alpha on Runx2-activated osteogenic gene transcription and the molecular mechanism. We found that TNF-alpha inhibited BMP-2-induced osteogenic marker expression and both the spontaneous and BMP-2-induced Runx2 expression. TNF-alpha stimulation or overexpression of nuclear factor-kappa B (NF-kappaB) p65 subunit repressed the Runx2-activated BSP and osteocalcin (OC) transcriptions. The Runx2 induced 9.0 kb BSP promoter activity was attenuated by TNF-alpha or p65, while the OSE2 activity was not affected. Besides, blockage of NF-kappaB by IkappaBalpha overexpression eliminated these inhibitory effects of TNF-alpha on Runx2 signaling. These results suggest that in murine bone marrow stromal cells undergoing osteogenic differentiation, TNF-alpha and it activated NF-kappaB pathway inhibit the expression of Runx2 gene, and suppress the Runx2-mediated osteogenic gene transcription via the 9.0 kb BSP promoter. PMID- 27401009 TI - Development and Validation of the COMPLES Score for Differentiating Between Tuberculous Effusions with Low Pleural pH or Glucose and Complicated Parapneumonic Effusions. AB - BACKGROUND: The frequency of "complicated" pleural effusions (CPE) (i.e., pleural fluid pH <= 7.2 and/or glucose <=60 mg/dL) of tuberculous origin (CTPE) is not well reported. This study aims to quantify their prevalence, and develop a score to differentiate CTPE from complicated parapneumonic effusions (CPPE). METHODS: Retrospective analysis of databases from three Spanish hospitals which included patients with CTPE and CPPE. Forty percent of the study population served to generate a scoring system (COMPLES, COMplicated PLeural Effusion Score) that was further validated in the remaining 60 %. RESULTS: During the study period (1992 2015) 549 patients were diagnosed with tuberculous effusions and 434 parapneumonic effusions, of whom 25 and 64 %, respectively, had CPE. COMPLES was based on the combination of pleural fluid adenosine deaminase (ADA), the percentage of mononuclear cells (MNC %), pH, and age. The cutoff values and assigned scores were: ADA (<46 IU/L [0 points], 46-100 IU/L [4 points], >=100 IU/L [6 points]), MNC % (<10 % [0 points], 10-50 [3 points], >50 [8 points]), pH (<7.07 [0 points], 7.07-7.20 [3 points], >7.20 [5 points]), and age (>=30 [0 points], <30 years [3 points]). A sum of 12 or more points had 97 % sensitivity, 92 % specificity, likelihood ratio positive 12.3, likelihood ratio negative 0.03, and area under the curve of 0.947 for identifying CTPE versus CPPE in the validation set. CONCLUSIONS: CPE is not an unusual presentation of tuberculosis. A simple new scoring system provides a reliable tool for differentiating between CTPE and CPPE. PMID- 27401010 TI - Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever. AB - BACKGROUND: Dengue hemorrhagic fever (DHF) is a severe life-threatening form of dengue infection. Low platelet count is one of the characteristic clinical manifestations in patients with severe dengue. However, little is known about genetic factors in the host that cause low platelet count in patients with dengue. METHODS: A previous genome-wide association study of hematological and biochemical traits identified single nucleotide polymorphisms (SNPs) associated with low platelet count in healthy subjects. To examine the possible association of these SNPs with DHF, 918 Thai patients with dengue [509 patients with DHF and 409 with dengue fever (DF)] were genotyped for five SNPs: rs5745568 in BAK1, rs6141 in THPO, rs6065 in GP1BA, rs739496 in SH2B3, and rs385893 in RCL1. In addition, rs4804803 in CD209, that has been reported to be associated with dengue infection, was also genotyped to examine if rs4804803 affects the association detected in this study. RESULTS: The allele frequencies of each SNP were compared between the DHF and DF groups. Among the five SNPs, the G allele of rs5745568 in BAK1 was significantly associated with a risk for DHF [P = 0.006 and crude odd ratio (95 % confidence interval) = 1.32 (1.09-1.60)]. The association of this allele with DHF was also significant in a logistic regression analysis adjusted for age, sex, hospital (i.e., geographic region), immune status (i.e., primary or secondary infection), and virus serotype [P = 0.016 and adjusted odd ratio (95 % confidence interval) = 1.29 (1.05-1.58)]. The result was not influenced by rs4804803 [P = 0.0167 and adjusted OR (95 % CI) = 1.29 (1.05-1.58)]. No other SNPs including rs4804803 showed significant association. CONCLUSIONS: The low level constitutive production of platelets caused by the G allele of rs5745568 seems to increase the risk of bleeding in dengue infection. Our results suggest that BCL-2 homologous antagonist/killer (BAK) protein, encoded by BAK1, plays a crucial role in the pathogenesis of DHF. PMID- 27401011 TI - The visible and hidden blood loss of Asia proximal femoral nail anti-rotation and dynamic hip screw in the treatment of intertrochanteric fractures of elderly high risk patients: a retrospective comparative study with a minimum 3 years of follow-up. AB - BACKGROUND: The purpose of this study was to evaluate whether PFNA-II (Asia proximal femoral nail anti-rotation) and DHS (dynamic hip screw) carry substantial post-operative hidden blood loss and to compare PFNA-II with DHS in terms of post-operative hidden blood loss in elderly high-risk patients with intertrochanteric femur fractures(IFFs). METHODS: The clinical data from Jan 2005 to Apr 2015 of 186 patients with PFNA-II and 177 patients with DHS were analyzed retrospectively. Indexes including pre- and post-operative blood routine, intra- and post-operative blood loss and blood transfusion situation were analyzed. The situation of perioperative blood loss (visible and hidden) was assessed. RESULTS: The intra-operative blood loss in the PFNA-II group was 34.7 +/- 2.5 ml, the post operative visible blood loss was 54.7 +/- 2.5 ml, and the hidden blood loss was 277.2 +/- 7.6 ml. In the DHS group, the intra-operative blood loss was 102.0 +/- 7.0 ml, the post-operative visible blood loss was 78.8 +/- 4.7 ml, and the hidden blood loss was 139.3 +/- 9.6 ml. The intra-operative blood loss and the post operative visible blood loss in the PFNA-II group were significantly less than in the DHS group (p < 0.01). However, the post-operative hidden blood loss and the total blood loss in the PFNA-II group were larger than in the DHS group (p < 0.01). CONCLUSION: This study demonstrated that with PFNA-II and DHS, much post operative hidden blood loss exists in the treatment of intertrochanteric fractures in elderly high-risk patients and DHS is more favourable than PFNA-II in terms of post-operative hidden blood loss. PMID- 27401012 TI - Effect of hydrogen in controlling the structural orientation of ZnO:Ga:H as transparent conducting oxide films suitable for applications in stacked layer devices. AB - Hydrogenation of the ZnO:Ga network has been chosen as a promising avenue to further upgrade the optoelectronic and structural properties of the films. With an optimum incorporation of hydrogen at a low substrate temperature (TS = 100 degrees C) in RF magnetron sputtering plasma, the ZnO:Ga:H film, with a large crystallite size (~17 nm) and improved crystallinity along the optimally preferred c-axis orientation with respect to both the <100> (I<002>/I<100> ~ 74) and <103> (I<002>/I<103> ~ 10) directions, attains a high electrical conductivity (sigma ~ 1.5 * 10(3)) and ~90% visible range optical transmission that yields a wide optical band gap of ~3.78 eV. The dominant c-axis orientation of the ZnO crystals exhibits a distinct UV luminescence band at ~340 nm that arises as a result of the typical exciton emission or near-band-edge emission, which occurs due to the recombination of photo-generated electrons and holes in the valence band or in traps near the valence band. Vacancies created by the out diffusion of oxygen from the network induces the growth along the <103> crystallographic orientation. With the introduction of an optimum amount of hydrogen into the network, the VO peak (OII) in the O 1s XPS spectrum significantly reduces in intensity while the Zn-OH peak (OIII) increases, indicating enhanced surface absorption of O species, which causes the improvement of c-axis orientation. The increase in the conductivity has been attributed to the centers assigned to isolated hydrogen atoms in the anti-bonding sites (ABO) or bond-centered sites of O-Zn bonds (BC), and Zn vacancies passivated by one or two hydrogen atoms. Hydrogen-induced dopant-like defects in the film and the associated large amount of tensile stress developed within the network has been correlated to the high conductivity and the wide band gap of the ZnO:Ga:H film due to the decreased repulsion between the O 2p and the Zn 4s bands and the Burstein-Moss effect as a consequence of the increased carrier concentration. Highly conducting and transparent c-axis oriented ZnO:Ga:H films grown by a device compatible process at a low TS are extremely useful for various stacked layer thin film devices, including solar cells. PMID- 27401013 TI - An external validation of models to predict the onset of chronic kidney disease using population-based electronic health records from Salford, UK. AB - BACKGROUND: Chronic kidney disease (CKD) is a major and increasing constituent of disease burdens worldwide. Early identification of patients at increased risk of developing CKD can guide interventions to slow disease progression, initiate timely referral to appropriate kidney care services, and support targeting of care resources. Risk prediction models can extend laboratory-based CKD screening to earlier stages of disease; however, to date, only a few of them have been externally validated or directly compared outside development populations. Our objective was to validate published CKD prediction models applicable in primary care. METHODS: We synthesised two recent systematic reviews of CKD risk prediction models and externally validated selected models for a 5-year horizon of disease onset. We used linked, anonymised, structured (coded) primary and secondary care data from patients resident in Salford (population ~234 k), UK. All adult patients with at least one record in 2009 were followed-up until the end of 2014, death, or CKD onset (n = 178,399). CKD onset was defined as repeated impaired eGFR measures over a period of at least 3 months, or physician diagnosis of CKD Stage 3-5. For each model, we assessed discrimination, calibration, and decision curve analysis. RESULTS: Seven relevant CKD risk prediction models were identified. Five models also had an associated simplified scoring system. All models discriminated well between patients developing CKD or not, with c statistics around 0.90. Most of the models were poorly calibrated to our population, substantially over-predicting risk. The two models that did not require recalibration were also the ones that had the best performance in the decision curve analysis. CONCLUSIONS: Included CKD prediction models showed good discriminative ability but over-predicted the actual 5-year CKD risk in English primary care patients. QKidney, the only UK-developed model, outperformed the others. Clinical prediction models should be (re)calibrated for their intended uses. PMID- 27401014 TI - Body Composition and Bone Mineral Density in Patients With Heart Failure. AB - The purpose of this study was to examine associations among bone mineral density, osteopenia/osteoporosis, body mass index (BMI), and body composition in patients with heart failure (HF). A total of 119 patients (age = 61 +/- 12 years, 65% male) underwent dual-energy X-ray absorptiometry scans to determine bone mineral density and body composition. In multivariable linear regressions, BMI, relative skeletal muscle index (RSMI), and mineral-free lean mass were positively associated with total body bone mineral density. Mineral-free lean mass was most strongly associated with bone mineral density (beta = .398). In multivariable logistic regressions, higher BMI, RSMI, and mineral-free lean mass were associated with lower odds for osteopenia/osteoporosis. Fat mass was not associated with total body bone mineral density or osteopenia/osteoporosis. These results suggest that muscle mass may be the important component of body mass associated with bone mineral density in patients with HF. PMID- 27401015 TI - Compassion training in healthcare: what are patients' perspectives on training healthcare providers? AB - BACKGROUND: The purpose of this qualitative study was to investigate advanced cancer patients' perspectives on the importance, feasibility, teaching methods, and issues associated with training healthcare providers in compassionate care. METHODS: This study utilized grounded theory, a qualitative research method, to develop an empirical understanding of compassion education rooted in direct patient reports. Audio-recorded semi-structured interviews were conducted to obtain an in-depth understanding of compassion training from the perspectives of hospitalized advanced cancer patients (n = 53). Data were analyzed in accordance with grounded theory to determine the key elements of the underlying theory. RESULTS: Three overarching categories and associated themes emerged from the data: compassion aptitude, cultivating compassion, and training methods. Participants spoke of compassion as an innate quality embedded in the character of learners prior to their healthcare training, which could be nurtured through experiential learning and reflective practices. Patients felt that the innate qualities that learners possessed at baseline were further fashioned by personal and practice experiences, and vocational motivators. Participants also provided recommendations for compassion training, including developing an interpersonal relationship with patients, seeing the patient as a person, and developing a human connection. Teaching methods that patients suggested in compassion training included patient-centered communication, self-reflection exercises, and compassionate role modeling. CONCLUSIONS: This study provides insight on compassion training for both current and future healthcare providers, from the perspectives of the end recipients of healthcare provider training - patients. Developing a theoretical base for patient centred, evidence-informed, compassion training is a crucial initial step toward the further development of this core healthcare competency. PMID- 27401017 TI - Contribution of time-varying measures of health behaviours to socioeconomic inequalities in mortality: how to understand the underlying mechanisms? AB - A higher prevalence of unhealthy behaviours in lower socioeconomic groups contributes to socioeconomic inequalities in mortality. Recent cohort studies suggest that the contribution of health behaviours to socioeconomic inequalities in mortality is larger when measured repeatedly over time ('time-varying') instead of once only ('time-fixed'). Explanations for a larger contribution of health behaviours, however, are hardly discussed in the current literature, and appear to be more complex than a widening of inequalities in health behaviours over time alone. We describe the use of time-varying health behaviours to examine socioeconomic inequalities in mortality, systematically listing underlying mechanisms that may cause differences between time-varying and time-fixed models, and show that these mechanisms may be specific for each health behaviour. The use of time-varying health behaviours advances our understanding of the explanation of socioeconomic inequalities in mortality, but underlying mechanisms must be carefully examined. PMID- 27401016 TI - Genetic diversity of Plasmodium falciparum in human malaria cases in Mali. AB - BACKGROUND: In Mali, Plasmodium falciparum malaria is highly endemic and remains stable despite the implementation of various malaria control measures. Understanding P. falciparum population structure variations across the country could provide new insights to guide malaria control programmes. In this study, P. falciparum genetic diversity and population structure in regions of varying patterns of malaria transmission in Mali were analysed. METHODS: A total of 648 blood isolates adsorbed onto filter papers during population surveillance surveys (December 2012-March 2013, October 2013) in four distinct sites of Mali were screened for the presence of P. falciparum via quantitative PCR (qPCR). Multiple loci variable number of tandem repeats analysis (MLVA) using eight microsatellite markers was then performed on positive qPCR samples. Complete genotypes were then analysed for genetic diversity, genetic differentiation and linkage disequilibrium. RESULTS: Of 156 qPCR-positive samples, complete genotyping of 112 samples was achieved. The parasite populations displayed high genetic diversity (mean He = 0.77), which was consistent with a high level of malaria transmission in Mali. Genetic differentiation was low (FST < 0.02), even between sites located approximately 900 km apart, thereby illustrating marked gene flux amongst parasite populations. The lack of linkage disequilibrium further revealed an absence of local clonal expansion, which was corroborated by the genotype relationship results. In contrast to the stable genetic diversity level observed throughout the country, mean multiplicity of infection increased from north to south (from 1.4 to 2.06) and paralleled malaria transmission levels observed locally. CONCLUSIONS: In Mali, the high level of genetic diversity and the pronounced gene flux amongst P. falciparum populations may represent an obstacle to control malaria. Indeed, results suggest that parasite populations are polymorphic enough to adapt to their host and to counteract interventions, such as anti-malarial vaccination. Additionally, the panmictic parasite population structure imply that resistance traits may disseminate freely from one area to another, making control measures performed at a local level ineffective. PMID- 27401018 TI - Developmental Exposure to Environmental Chemicals and Metabolic Changes in Children. AB - The incidence of childhood obesity, type 2 diabetes, and other forms of metabolic disease have been rising over the past several decades. Although diet and physical activity play important roles in these trends, other environmental factors also may contribute to this significant public health issue. In this article, we discuss the possibility that widespread exposure to endocrine disrupting chemicals (EDCs) may contribute to the development of metabolic diseases in children. We summarize the epidemiological evidence on exposure to environmental chemicals during early development and metabolic outcomes in infants and children. Prenatal exposure to EDCs, particularly the persistent organic pollutant DDT and its metabolite DDE, may influence growth patterns during infancy and childhood. The altered growth patterns associated with EDCs vary according to exposure level, sex, exposure timing, pubertal status, and age at which growth is measured. Early exposure to air pollutants also is linked to impaired metabolism in infants and children. As a result of these and other studies, professional health provider societies have called for a reduction in environmental chemical exposures. We summarize the resources available to health care providers to counsel patients on how to reduce chemical exposures. We conclude with a discussion of environmental policies that address chemical exposures and ultimately aim to improve public health. PMID- 27401020 TI - Dihydroartemisinin induces apoptosis in human gastric cancer cell line BGC-823 through activation of JNK1/2 and p38 MAPK signaling pathways. AB - Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is associated with a broad range of biological properties including antitumor activity. However, the effect of DHA on gastric cancer has not been clearly clarified. The aim of this study was to investigate the role and mechanism of DHA in human gastric cancer cell line BGC-823. Cell viability was assessed by MTT assay. Cell apoptosis was analyzed with flow cytometry. The expressions of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK) and their phosphorylated forms as well as apoptosis related proteins were examined by western blot analysis. The results demonstrated that DHA inhibited cell viability of BGC-823 cells in a dose and time-dependent manner. DHA treatment upregulated the expression of Bax, cleaved caspase-3 and -9, and degraded form of PARP, and downregulated the Bcl-2 expression and Bcl-2/Bax ratio. Meanwhile, DHA increased the phosphorylation of ERK1/2, JNK1/2 and p38 MAPK. Synthetic inhibitors of JNK1/2 or p38 MAPK kinase activity, but not inhibitor of ERK1/2, significantly abolished the DHA-induced activation of caspase-3 and -9. In vivo tumor-suppression assay further indicated that DHA displayed significant inhibitory effect on BGC-823 xenografts in tumor growth. These results indicate that DHA induces apoptosis of BGC-823 cells through JNK1/2 and p38 MAPK signaling pathways and DHA could serve as a potential additional chemotherapeutic agent for treatment of gastric cancer. PMID- 27401019 TI - Young Adult Utilization of a Smoking Cessation Website: An Observational Study Comparing Young and Older Adult Patterns of Use. AB - BACKGROUND: There is little research on how young adults or young adult subgroups utilize and engage with Web-based cessation interventions when trying to quit smoking. Addressing this knowledge gap is important to identify opportunities to optimize the effectiveness of online cessation programs across diverse young adult users. OBJECTIVE: This study examines utilization of the BecomeAnEX.org smoking cessation website among young adults and young adult subgroups compared with older adults to identify patterns of use by age, gender, and race/ethnicity. METHODS: Study participants were 5983 new registered users on a free smoking cessation website who were aged 18 to 70 years. Website utilization was tracked for 6 months; metrics of use included website visits, pages per visit, length of visit, and interaction with specific website features. Differences in website use by age were examined via bivariate analyses and multivariate logistic regression adjusted for age, gender, and race/ethnicity. Interactions were examined to determine differences by gender and race/ethnicity within young (18- to 24-year olds and 25- to 34-year-olds) and older (35 years and older) adult segments. RESULTS: A greater percentage of young adults aged 18 to 34 years visited the site only once compared with older adults aged 35 years and older (72.05% vs 56.59%, respectively; P<.001). Young adults also spent less time on the site and viewed fewer pages than older adults. In adjusted analyses, young adults were significantly less likely than older adults to visit the site more than once (18 24 years: adjusted odds ratio [AOR] 0.58, 95% CI 0.49-0.68, P<.001; 25-34 years: AOR 0.56, 95% CI 0.50-0.64, P<.001), spend more than 3 minutes on the site (18-24 years: AOR 0.67, 95% CI 0.57-0.79, P<.001; 25-34 years: AOR 0.56, 95% CI 0.49 0.64, P<.001), view 12 or more pages (18-24 years: AOR 0.72, 95% CI 0.61-0.83; P<.001; 25-34 years: AOR 0.67, 95% CI 0.59-0.76, P<.001), utilize the BecomeAnEX.org community (18-24 years: AOR 0.61, 95% CI 0.48-0.79, P<.001; 25-34 years: AOR 0.73, 95% CI 0.60-0.88, P<.001), or utilize Separation Exercises (18 24 years: AOR 0.68, 95% CI 0.51-0.89, P<.01; 25-34 years: AOR 0.77, 95% CI 0.63 0.94, P<.01). Gender differences in utilization were more pronounced among young adults compared with older adults, with lower levels of utilization among young men than young women. For all age groups, utilization was higher among whites and African Americans than among Hispanics and other racial minorities, with one exception-BecomeAnEX.org community utilization was significantly higher among Hispanic young adults compared with white and African American young adults. CONCLUSIONS: Results point to important areas of inquiry for future research and development efforts. Research should focus on enhancing demand and increasing engagement among younger adults and men, examining strategies for capitalizing on young adult developmental needs, and increasing utilization of effective site features among diverse young adult users. PMID- 27401021 TI - Trans-aortic Alfieri stitch at the time of septal myectomy for hypertrophic obstructive cardiomyopathy. AB - BACKGROUND: Systolic anterior motion (SAM) of the mitral valve, left ventricular outflow tract (LVOT) obstruction, and mitral regurgitation (MR) are known adverse outcomes that can occur after septal myectomy for hypertrophic obstructive cardiomyopathy. The objective of this study was to describe outcomes of a surgical technique to prevent these complications. METHODS: We have adopted a technique where we place an Alfieri stitch in the mitral valve through the aortotomy while performing septal myectomy. A retrospective review was performed and outcomes associated with this technique were noted. RESULTS: Twenty-four patients underwent septal myectomy and mitral valve repair using this technique. Mean age was 57 +/- 10 years. Twenty patients were in class III/IV heart failure, and all had documented SAM. Mean LVOT gradient improved from 78 +/- 48 mmHg preoperatively to 19 +/- 20 mmHg after myectomy (p < 0.001). No patients had postoperative SAM, and no patients required a second aortic crossclamping for mitral repair. Seventeen of 19 patients with >=mild MR had improvement in MR. During follow-up, 16 patients had no/trivial MR, seven had mild MR, and one had moderate MR. The mean postoperative mitral gradient was 4.5 +/- 3.0 mmHg. Thirteen patients had postoperative complications including one death in a patient who developed a ventricular septal defect. CONCLUSIONS: Trans-aortic Alfieri stitch placement during septal myectomy is feasible in most cases as an additional tool to improve MR and minimize SAM. This technique may have a role in addressing mitral disease, such as a long anterior leaflet or fibrotic mitral valve, at the time of myectomy without the need for left atriotomy for mitral exposure. PMID- 27401022 TI - Effects of Pore Size on the Osteoconductivity and Mechanical Properties of Calcium Phosphate Cement in a Rabbit Model. AB - Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200-300 um, Group B: 300-450 um, Group C: 450-600 um, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo. PMID- 27401024 TI - Ultra high-frequency ultrasound: New capabilities for nail anatomy exploration. AB - Recent development of ultra high-resolution ultrasound systems, with frequencies as high as 70 MHz and capability resolution as fine as 30 MUm, could permit new diagnostic applications to small parts. A variety of superficial targets within the first 1 cm of the skin surface could be imaged, including dermatological applications such as assessment of skin layers, hair follicles and the nail unit. Nail disorders are frequent but they are diagnosed mainly based on clinical examination; although biopsies and scrapings can provide clinically significant information, most patients do not perceive biopsies positively. To image the skin layer and annexes is often difficult with conventional ultrasound but, because of anatomical details obtained with the newest systems, this method holds great promise for addressing important biomedical applications offering unique advantages over the existing non-invasive imaging modalities. This will enable physicians to assess and manage the conditions involving the nails of a large and growing segment of the population in a better way. PMID- 27401023 TI - A qualitative evaluation of a novel intervention using insight into tobacco industry tactics to prevent the uptake of smoking in school-aged children. AB - BACKGROUND: Evidence from the US Truth campaign suggests that interventions focusing on tobacco industry tactics can be effective in preventing smoking uptake by children. Operation Smoke Storm is the first school-based intervention based on this premise and comprises three classroom sessions in which students act as secret agents uncovering tobacco industry tactics through videos, quizzes, discussions, and presentations. We report a qualitative evaluation of its acceptability. METHODS: We conducted eight focus groups with 79 students aged 11 12 who participated in Operation Smoke Storm at two UK schools in Autumn 2013, and 20 interviews with teachers who delivered the intervention. These were digitally audio-recorded, transcribed verbatim and analysed using the framework method. RESULTS: Students enjoyed the secret agent scenario and reported acquiring new knowledge about smoking and the tobacco industry, which seemed to strengthen their aversion to smoking. Teachers felt confident delivering the 'off the shelf' resource, although they would have welcomed more background information about the topic and guidance on steering discussions. Teachers highlighted a need for the resource to be flexible and not dependent on lesson length, teacher confidence, or expertise. Students and teachers endorsed the idea of developing a booster component for older students and supported the development of printed information complementing the resource to encourage parents to support their child not to smoke. CONCLUSIONS: These findings demonstrate that Operation Smoke Storm can be delivered by teachers to raise awareness about smoking-related issues. The ideas and issues raised are now being used to improve and extend the resource for further evaluation. PMID- 27401025 TI - The trajectory of Pediatric Otolaryngology. PMID- 27401026 TI - Varicocele among infertile men in Qatar. AB - Objective of this retrospective study was to assess the presence and clinical grade of varicocele among Qatari and non-Qatari men evaluated for infertility. Diagnosis of varicocele was performed clinically and confirmed via colour Doppler ultrasonography. A total of 455 infertile male patients (mean age 36.3 +/- 7.6 years) were divided into either Qatari (n = 91, mean age 37.3 +/- 9.1 years) or non-Qatari (n = 364, mean age 36.0 +/- 7.1 years) groups. Among all patients, 43.1% (n = 196) were confirmed to have varicocele, of which 40 were Qatari and 156 non-Qatari. Among all patients, 171 (37.6%) presented with left-sided varicocele and 25 (5.5%) with bilateral varicocele. Of the 196 patients with varicocele, grade I was given to 40 (20.4%), grade II to 68 (34.7%) and grade III to 88 (44.9%). Grade II and III varicocele were seen significantly more frequently than grade I among all patients and non-Qatari patients (p < .05). Grade II varicocele was seen more frequently than grades I or III among Qatari patients, but difference was not significant. Grade III was seen significantly more frequently than grade I among patients with secondary infertility (p < .05). Varicocele is an important health issue in Qatar among both Qatari and non-Qatari men. PMID- 27401027 TI - Comparative study of Cronobacter identification according to phenotyping methods. AB - BACKGROUND: Microbiological criteria applied to powdered infant formula (PIF) require the absence of all Cronobacter spp. Consequently, misidentification of isolates from finished products can lead to significant financial losses for manufacturers and could increase the risk of neonatal infection. Biochemical identification of suspect isolates using commercially available test panels is recommended for use by PIF manufacturers by both the US FDA and ISO standard methods for Cronobacter species; however, phenotyping can be unreliable, particularly for a genus such as Cronobacter where the taxonomy has been subject to frequent changes. This study compared the predicted identification by commonly used phenotyping kits (API20E and ID32E) for over 240 strains of Cronobacter from diverse sources, which had been identified using DNA sequence analysis. In 2015, the databases associated with the API20E and ID32E biochemical test panels were updated, including the recognition of the Cronobacter genus. Thus, the identifications from multiple versions the databases were compared to each other and to identifications based on DNA sequencing methods. RESULTS: Using previous versions of the API20E database, 90.0 % of strains (216/240) resulted in a match for the species identification; however, version 5.0 produced matches for only 82.3 % of strains (237/288). Similarly, the update to version 4.0 in the ID32E database caused the percentage of matches to drop from 88.9 % (240/270) to 43.2 % (139/322). A smaller study showed that the Vitek GN system identified all 14 strains, belonging all seven Cronobacter species, as members of the 'C. sakazakii group,' but also attributed three strains of Franconibacter helveticus and F. pulveris to this group. In silco analysis of a PCR-based method targeting ompA predicted that amplification would only occur with Cronobacter species and this method may be a feasible alternative to biochemical phenotyping. CONCLUSIONS: These results indicate that commercially available biochemical test panels are not sufficiently reliable for speciation of Cronobacter isolates. Although DNA sequence based methods would be the more reliable approach; however, this is not currently feasible for many food microbiology laboratories. Instead, a previously published PCR-based method targeting ompA is suggested as an alternative for identification of Cronobacter species based on in silico analysis. PMID- 27401028 TI - A revolution in preventing fatal craniovertebral junction injuries: lessons learned from the Head and Neck Support device in professional auto racing. AB - Fatal craniovertebral junction (CVJ) injuries were the most common cause of death in high-speed motor sports prior to 2001. Following the death of a mutual friend and race car driver, Patrick Jacquemart (1946-1981), biomechanical engineer Dr. Robert Hubbard, along with race car driver and brother-in-law Jim Downing, developed the concept for the Head and Neck Support (HANS) device to prevent flexion-distraction injuries during high-velocity impact. Biomechanical testing showed that neck shear and loading forces experienced during collisions were 3 times the required amount for a catastrophic injury. Crash sled testing with and without the HANS device elucidated reductions in neck tension, neck compression, head acceleration, and chest acceleration experienced by dummies during high energy crashes. Simultaneously, motor sports accidents such as Dale Earnhardt Sr.'s fatal crash in 2001 galvanized public opinion in favor of serious safety reform. Analysis of Earnhardt's accident demonstrated that his car's velocity parallel to the barrier was more than 150 miles per hour (mph), with deceleration upon impact of roughly 43 mph in a total of 0.08 seconds. After careful review, several major racing series such as the National Association for Stock Car Auto Racing (NASCAR) and Championship Auto Racing Team (CART) made major changes to ensure the safety of drivers at the turn of the 21st century. Since the rule requiring the HANS device in professional auto racing series was put in place, there has not been a single reported case of a fatal CVJ injury. PMID- 27401029 TI - Optimizing tissue perfusion during targeted temperature management. PMID- 27401030 TI - Method to assess the accuracy of scores in mortality prediction of trauma patients: Not only receiver operating characteristic curve. PMID- 27401032 TI - The concordance between the volume hotspot and the grade hotspot: a 3-D reconstructive model using the pathology outputs from the PROMIS trial. AB - OBJECTIVES: The rationale for directing targeted biopsy towards the centre of lesions has been questioned in light of prostate cancer grade heterogeneity. In this study, we assess the assumption that the maximum cancer Gleason grade (Gleason grade hotspot) lies within the maximum dimension (volume hotspot) of a prostate cancer lesion. METHODS: 3-D histopathological models were reconstructed using the outputs of the 5-mm transperineal mapping (TPM) biopsies used as the reference test in the pilot phase of Prostate Mri Imaging Study (PROMIS), a paired validating cohort study investigating the performance of multi-parametric magnetic resonance imaging (MRI) against transrectal ultrasound (TRUS) biopsies. The prostate was fully sampled with 5 mm intervals; each core was separately labelled, inked and orientated in space to register 3-D cancer lesions location. The data from the histopathology results were used to create a 3-D interpolated reconstruction of each lesion and identify the spatial coordinates of the largest dimension (volume hot spot) and highest Gleason grade (Gleason grade hotspot) and assess their concordance. RESULTS: Ninety-four men, with median age 62 years (interquartile range, IQR= 58-68) and median PSA 6.5 ng ml(-1) (4.6-8.8), had a median of 80 (I69-89) cores each with a median of 4.5 positive cores (0-12). In the primary analysis, the prevalence of homogeneous lesions was 148 (76%; 95% confidence interval (CI) +/-6.0%). In all, 184 (94+/-3.2%) lesions showed concordant hotspots and 11/47 (23+/-12.1%) of heterogeneous lesions showed discordant hotspots. The median 3-D distance between discordant hotspots was 12.8 mm (9.9-15.5). These figures remained stable on secondary analyses using alternative reconstructive assumptions. Limitations include a certain degree of error within reconstructed models. CONCLUSIONS: Guiding one biopsy needle to the maximum cancer diameter would lead to correct Gleason grade attribution in 94% of all lesions and 79% of heterogeneous ones if a true hit was obtained. Further correlation of histological lesions, their MRI appearance and the detectability of these hotspots on MRI will be undertaken once PROMIS results are released. PMID- 27401033 TI - Impact of the extent of extraprostatic extension defined by Epstein's method in patients with negative surgical margins and negative lymph node invasion. AB - BACKGROUND: To assess the impact of the degree of extraprostatic extension (EPE) on biochemical recurrence (BCR) and utility of the original Epstein's criteria to define EPE in a cohort of pT3aN0 without positive surgical margin (PSM). METHODS: A two-center retrospective analysis was performed on data from 490 pT3aN0 patients who underwent radical prostatectomy between 2000 and 2012. Patients with neoadjuvant and/or adjuvant therapy, detectable PSA and PSM were excluded. Our pathologists used Epstein's criteria to report the degree of EPE. When pathology reports did not reflect the terms 'focal' or 'established' (non-focal), slides were analyzed by a single genitourinary pathologist for final evaluation. The end point was defined by BCR. RESULTS: Selection criteria yielded 247 patients. Mean follow-up was 56.3+/-4.6 months; mean age at surgery was 62.5 years. Sixty-one (24.7%) patients experienced BCR during follow-up. Patients with focal extension had a 5-year recurrence-free survival of 89% versus 80% for those with non-focal extension (P=0.0018). In multivariate analysis, both pathologic Gleason score (hazard ratio 2.5; 95% confidence interval 1.4-4.5; P=0.002) and the extent of EPE (hazard ratio 1.8; 95% confidence interval 1.1-3.5; P=0.029) were significant predictors of BCR. CONCLUSIONS: The extent of EPE is an independent predictor of BCR in pT3aN0 prostate cancer without PSM. This study reinforces the utility of the subjective Epstein approach already adopted by most pathologists for quantification of the extent of EPE. PMID- 27401034 TI - A Comparison of Outcomes for Cord Blood Transplantation and Unrelated Bone Marrow Transplantation in Adult Aplastic Anemia. AB - Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8-matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio [HR], .55; 95% confidence interval [CI], .32 to .94; P = .029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR, .55; 95% CI, .29 to 1.02) or 6/8-matched UBMT (HR, .67; 95% CI, .32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old,survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8 matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8 matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. PMID- 27401035 TI - Kidney-on-a-chip technology for renal proximal tubule tissue reconstruction. AB - The renal proximal tubule epithelium is responsible for active secretion of endogenous and exogenous waste products from the body and simultaneous reabsorption of vital compounds from the glomerular filtrate. The complexity of this transport machinery makes investigation of processes such as tubular drug secretion a continuous challenge for researchers. Currently available renal cell culture models often lack sufficient physiological relevance and reliability. Introducing complex biological culture systems in a 3D microfluidic design improves the physiological relevance of in vitro renal proximal tubule epithelium models. Organ-on-a-chip technology provides a promising alternative, as it allows the reconstruction of a renal tubule structure. These microfluidic systems mimic the in vivo microenvironment including multi-compartmentalization and exposure to fluid shear stress. Increasing data supports that fluid shear stress impacts the phenotype and functionality of proximal tubule cultures, for which we provide an extensive background. In this review, we discuss recent developments of kidney-on a-chip platforms with current and future applications. The improved proximal tubule functionality using 3D microfluidic systems is placed in perspective of investigating cellular signalling that can elucidate mechanistic aberrations involved in drug-induced kidney toxicity. PMID- 27401036 TI - Local-anesthetic like inhibition of the cardiac sodium channel Nav1.5 alpha subunit by 5-HT3 receptor antagonists. AB - 5-hydroxytryptamine 3 receptor (5-HT3 receptor) antagonists are administered for prevention and therapy of nausea and vomiting. Although regarded as safe therapeutics, they can also provoke arrhythmias by prolonging the QRS interval. However, the mechanisms mediating this cardiotoxicity are poorly understood. Here we investigated effects of 5-HT3 receptor antagonists on the cardiac Na(+) channel Nav1.5. We explored the interaction of dolasetron, tropisetron, granisetron and ondansetron on the human alpha-subunit Nav1.5 heterologously expressed in HEK293 cells. Sodium currents were explored by means of whole-cell patch clamp recordings. All four substances inhibited the Nav1.5 in a concentration and state-dependent manner. Dolasetron displayed the lowest blocking efficacy, and tropisetron was the most potent blocker with a half maximum blocking concentration of 18uM for tonic block of inactivated channels. Tropisetron was also the most potent use-dependent inhibitor, and it also induced a strong open -channel block. Both tonic and use-dependent block by tropisetron were abbreviated on the local-anesthetic insensitive mutant Nav1.5-F1760A. Co administration of tropisetron and the local anesthetic bupivacaine or the hypnotic propofol augmented inhibition of Nav1.5. Our data demonstrate that 5-HT3 receptor antagonists induce a local-anesthetic like inhibition of Nav1.5, and that they display different blocking efficacies. Reports on a relevant cardiotoxicity of dolasetron as opposed to other 5-HT3 receptor antagonists do not seem to correlate with a block of Nav1.5. As inhibition of Nav1.5 was enhanced by propofol and bupivacaine however, it is possible that a combined administration of Na(+) channel blockers and 5-HT3 receptor antagonists can provoke arrhythmias. PMID- 27401037 TI - Ergocalciferol versus calcitriol for controlling chronic kidney disease mineral bone disorder in stage 3 to 5 CKD: A randomized controlled trial. AB - To compare the efficacy and safety of ergocalciferol and calcitriol in stage 3 to 5 chronic kidney disease (CKD) patients, a randomized, prospective, controlled, open-labeled study was designed. 204 patients were enrolled into the present study with following-up duration of 33.2+/-3.8 months. Patients in Group VitD2 (n=104) and Group aVitD3 (n=100) were treated by ergocalciferol and calcitriol, respectively. The 25-hydroxyvitamin D levels of group VitD2 increased significantly from 15.14+/-7.46 to 37.32+/-10.49ng/ml (P<0.001, t=-19.692) and increased more (P<0.001, t=-14.982) than those of group aVitD3, which increased from 14.90+/-6.15 to 18.08+/-7.55ng/ml. Maintenance target levels of serum calcium, phosphorus, and intact parathyroid hormone as the primary outcome measure did not show significant difference in frequencies between two groups. In summary, treatment of CKD-mineral and bone disorders in CKD patients at stages 3 to 5 using ergocalciferol has a similar long-term efficacy and safety profile as calcitriol. PMID- 27401038 TI - CD123-Engager T Cells as a Novel Immunotherapeutic for Acute Myeloid Leukemia. AB - Immunotherapy with CD123-specific T-cell engager proteins or with T cells expressing CD123-specific chimeric antigen receptors is actively being pursued for acute myeloid leukemia. T cells secreting bispecific engager molecules (ENG-T cells) may present a promising alternative to these approaches. To evaluate therapeutic potential, we generated T cells to secrete CD123/CD3-bispecific engager molecules. CD123-ENG T cells recognized primary acute myeloid leukemia (AML) cells and cell lines in an antigen-dependent manner as judged by cytokine production and/or tumor killing, and redirected bystander T cells to AML cells. Infusion of CD123-ENG T cells resulted in regression of AML in xenograft models conferring a significant survival advantage of treated mice in comparison to mice that received control T cells. At high effector to target ratios, CD123-ENG T cells recognized normal hematopoietic stem and progenitor cells (HSPCs) with preferential recognition of HSPCs from cord blood compared to bone marrow. We therefore introduced the CD20 suicide gene that can be targeted in vivo with rituximab into CD123-ENG T cells. The expression of CD20 did not diminish the anti-AML activity of CD123-ENG T cells, but allowed for rituximab-mediated ENG-T cell elimination. Thus, ENG-T cells coexpressing CD20 suicide and CD123 engager molecules may present a promising immunotherapeutic approach for AML. PMID- 27401039 TI - Elimination of Latently HIV-infected Cells from Antiretroviral Therapy-suppressed Subjects by Engineered Immune-mobilizing T-cell Receptors. AB - Persistence of human immunodeficiency virus (HIV) in a latent state in long-lived CD4+ T-cells is a major barrier to eradication. Latency-reversing agents that induce direct or immune-mediated cell death upon reactivation of HIV are a possible solution. However, clearance of reactivated cells may require immunotherapeutic agents that are fine-tuned to detect viral antigens when expressed at low levels. We tested the antiviral efficacy of immune-mobilizing monoclonal T-cell receptors against viruses (ImmTAVs), bispecific molecules that redirect CD8+ T-cells to kill HIV-infected CD4+ T-cells. T-cell receptors specific for an immunodominant Gag epitope, SL9, and its escape variants were engineered to achieve supraphysiological affinity and fused to a humanised CD3 specific single chain antibody fragment. Ex vivo polyclonal CD8+ T-cells were efficiently redirected by immune-mobilising monoclonal T-cell receptors against viruses to eliminate CD4+ T-cells from human histocompatibility leukocyte antigen (HLA)-A*0201-positive antiretroviral therapy-treated patients after reactivation of inducible HIV in vitro. The efficiency of infected cell elimination correlated with HIV Gag expression. Immune-mobilising monoclonal T-cell receptors against viruses have potential as a therapy to facilitate clearance of reactivated HIV reservoir cells. PMID- 27401041 TI - MUSR investigation of a new diluted magnetic semiconductor Li(Zn,Mn,Cu)As with Mn and Cu codoping at the same Zn sites. AB - We report the successful synthesis and characterization of a new type I-II-V bulk form diluted magnetic semiconductor (DMS) Li(Zn,Mn,Cu)As, in which charge and spin doping are decoupled via (Cu,Zn) and (Mn,Zn) substitution at the same Zn sites. Ferromagnetic transition temperature up to ~33 K has been observed with a coercive field ~40 Oe for the 12.5% doping level. MUSR measurements confirmed that the magnetic volume fraction reaches nearly 100% at 2 K, and the mechanism responsible for the ferromagnetic interaction in this system is the same as other bulk form DMSs. PMID- 27401040 TI - Structural Determinants of Sleeping Beauty Transposase Activity. AB - Transposases are important tools in genome engineering, and there is considerable interest in engineering more efficient ones. Here, we seek to understand the factors determining their activity using the Sleeping Beauty transposase. Recent work suggests that protein coevolutionary information can be used to classify groups of physically connected, coevolving residues into elements called "sectors", which have proven useful for understanding the folding, allosteric interactions, and enzymatic activity of proteins. Using extensive mutagenesis data, protein modeling and analysis of folding energies, we show that (i) The Sleeping Beauty transposase contains two sectors, which span across conserved domains, and are enriched in DNA-binding residues, indicating that the DNA binding and endonuclease functions of the transposase coevolve; (ii) Sector residues are highly sensitive to mutations, and most mutations of these residues strongly reduce transposition rate; (iii) Mutations with a strong effect on free energy of folding in the DDE domain of the transposase significantly reduce transposition rate. (iv) Mutations that influence DNA and protein-protein interactions generally reduce transposition rate, although most hyperactive mutants are also located on the protein surface, including residues with protein protein interactions. This suggests that hyperactivity results from the modification of protein interactions, rather than the stabilization of protein fold. PMID- 27401042 TI - Correction: beta-Sialon nanowires, nanobelts and hierarchical nanostructures: morphology control, growth mechanism and cathodoluminescence properties. AB - Correction for 'beta-Sialon nanowires, nanobelts and hierarchical nanostructures: morphology control, growth mechanism and cathodoluminescence properties' by Juntong Huang, et al., Nanoscale, 2014, 6, 424-432. PMID- 27401043 TI - Mechanical and material properties of cortical and trabecular bone from cannabinoid receptor-1-null (Cnr1(-/-)) mice. AB - The endocannabinoid system is known for its regulatory effects on bone metabolism through the cannabinoid receptors, Cnr1 and Cnr2. In this study we analysed the mechanical and material properties of long bones from Cnr1(-/-) mice on a C57BL/6 background. Tibiae and femora from 5- and 12-week-old mice were subjected to three-point bending to measure bending stiffness and yield strength. Elastic modulus, density and mineral content were measured in the diaphysis. Second moment of area (MOA2), inner and outer perimeters of the cortical shaft and trabecular fractional bone volume (BV/TV) were measured using micro-CT. In Cnr1( /-) males and females at both ages the bending stiffness was reduced due to a smaller MOA2. Bone from Cnr1(-/-) females had a greater modulus than wild-type controls, although no differences were observed in males. BV/TV of 12-week-old Cnr1(-/-) females was greater than controls, although no difference was seen at 5 weeks. On the contrary, Cnr1(-/-) males had the same BV/TV as controls at 12 weeks while they had significantly lower values at 5-weeks. This study shows that deleting Cnr1 decreases the amount of cortical bone in both males and females at 12-weeks, but increases the amount of trabecular bone only in females. PMID- 27401044 TI - In vivo tissue interaction between the transverse carpal ligament and finger flexor tendons. AB - The transverse carpal ligament (TCL) is a component of the flexor pulley system of the wrist, keeping the flexor tendons in place by resisting their volar displacement. The purpose of this study was to investigate the in vivo biomechanical interaction between the TCL and flexor tendons in response to tendon tensioning with the wrist at various postures. In eight healthy subjects, the flexor digitorum superficialis and profundus tendons were tensioned by isometrically applying loads (5, 10, and 15N) to the index finger while the wrist posture was at 20 degrees extension, neutral, 20 degrees flexion, and 40 degrees flexion. The TCL and flexor tendons were imaged at the distal carpal tunnel cross section using ultrasound. The volar-dorsal positions of the tendons, TCL arch height, and TCL-tendon distances were calculated. With increasing wrist flexion, the flexor tendons moved volarly, the TCL arch height increased, and the TCL-tendon distances decreased, indicating that the flexor tendons contacted the TCL and pushed it volarly. The TCL-tendon interaction was amplified by the combination of finger loading and wrist flexion. This study provides in vivo evidence of the biomechanical interaction between the TCL and flexor tendons. Repetitive TCL-tendon interactions may implicate the interacting tissues and the median nerve resulting in tissue maladaptation and nerve compression. PMID- 27401046 TI - The identification of the relationship between the perceived social support, fatigue levels and maternal attachment during the postpartum period. AB - OBJECTIVE: This study aims to determinate the relationship between social support perceived by women, fatigue levels and maternal attachment in postpartum period. METHODS: The sample of this descriptive study consists of 181 women who gave birth in the study period. The data was collected by the socio-demographic characteristics forms; "Multidimensional Scale of Perceived Social Support" (MSPSS); "Multidimensional Assessment of Fatigue Scale" (MAFS) and "Maternal Attachment Scale" (MAS) on the postpartum first days and 30-40th days. RESULTS: MSPSS scores of women who had university or higher education, employed, had their first pregnancy, have 12 months or less between two pregnancies, were found to be significantly higher than others. MAS scores of women at the end of the postpartum first month were significantly increased. MAFS scores of women at the end of the postpartum first month were significantly decreased. The correlation between the fatigue levels and maternal attachment levels at the end of the postpartum first month was found to be negative and significant. CONCLUSION: In the postpartum period, the care of the mother should include social support, maternal attachment and fatigue assessment. Mothers should be encouraged to use social support resources. The continuity of social support systems should be provided. PMID- 27401045 TI - Closed-Loop Deep Brain Stimulation Effects on Parkinsonian Motor Symptoms in a Non-Human Primate - Is Beta Enough? AB - BACKGROUND: Incorporating feedback controls based on real-time measures of pathological brain activity may improve deep brain stimulation (DBS) approaches for the treatment of Parkinson's disease (PD). Excessive beta oscillations in subthalamic nucleus (STN) local field potentials (LFP) have been proposed as a potential biomarker for closed-loop DBS (CL-DBS). OBJECTIVE: In a non-human primate PD model we compared CL-DBS, which delivered stimulation only when STN LFP beta activity was elevated, to traditional continuous DBS (tDBS). METHODS: Therapeutic effects of CL-DBS and tDBS relative to the Off-DBS condition were evaluated via a clinical rating scale and objective measures of movement speed during a cued reaching task. RESULTS: CL-DBS was comparable to tDBS at reducing rigidity, while reducing the amount of time DBS was on by ~50%; however, only tDBS improved bradykinesia during the reaching behavior. This was likely due to reach-related reductions in beta amplitude that influence the timing and duration of stimulation in the CL-DBS condition. CONCLUSION: These results illustrate the potential utility of closed-loop DBS devices for PD based on STN beta LFP levels. They also point to possible consequences in behavioral tasks when restricting real-time sensing to a single LFP frequency that itself is modulated during performance of such tasks. The present study provides data that suggest alternate algorithms or more than one physiological biomarker may be required to optimize the performance of behavioral tasks and demonstrates the value of using multiple objective measures when evaluating the efficacy of closed-loop DBS systems. PMID- 27401047 TI - A study on reliability and validity of the Turkish version of the Face Anxiety Scale on mechanically-ventilated patients. AB - Mechanical ventilation treatment causes patient anxiety, such that for those people dependent on mechanical ventilation, it was suggested to self-evaluate anxiety levels using a scale. The aim of this study was to assess the reliability and validity of the Turkish version of the Face Anxiety Scale in order to evaluate general patient anxiety levels for those receiving mechanical ventilation in a cardiovascular surgery (CVS) intensive care unit (ICU). A survey was conducted between April and December 2015 with 99 patients in receipt of mechanical ventilation at the CVS-ICU of a military training hospital in Turkey. Patients' average age was 59.31+/-16.47 years (range 18-83 years), with 73.7% for males and 73.7% for those undergoing coronary artery bypass graft surgery. The average scores from the Face Anxiety Scale were 2.8+/-1.3. A statistically significant (positive) correlation was found between scores from the test and retest (r=0.87, p<0.001), which indicated that the scale was reliable. The relationship between the Face Anxiety Scale and Profile of the Mood States (POMS) of participants scored 0.89, corroborating the validity of the former (p<0.001). This study found that it was valuable for evaluating patient anxiety in those receiving mechanical ventilation. PMID- 27401048 TI - Clinical Activity Monitoring System (CATS): An automatic system to quantify bedside clinical activities in the intensive care unit. AB - Monitoring clinical activity at the bedside in the intensive care unit (ICU) can provide useful information to evaluate nursing care and patient recovery. However, it is labour intensive to quantify these activities and there is a need for an automated method to record and quantify these activities. This paper presents an automated system, Clinical Activity Tracking System (CATS), to monitor and evaluate clinical activity at the patient's bedside. The CATS uses four Microsoft Kinect infrared sensors to track bedside nursing interventions. The system was tested in a simulated environment where test candidates performed different motion paths in the detection area. Two metrics, 'Distance' and 'Dwell time', were developed to evaluate interventions or workload in the detection area. Results showed that the system can accurately track the intervention performed by individual or multiple subjects. The results of a 30-day, 24-hour preliminary study in an ICU bed space matched clinical expectations. It was found that the average 24-hour intervention is 22.0minutes/hour. The average intervention during the day time (7am-11pm) is 23.6minutes/hour, 1.4 times higher than 11pm-7am, 16.8minutes/hour. This system provides a unique approach to automatically collect and evaluate nursing interventions that can be used to evaluate patient acuity and workload demand. PMID- 27401049 TI - Efficacy of pneumodilation in achalasia after failed Heller myotomy. AB - BACKGROUND: Heller myotomy is an effective treatment for the majority of achalasia patients. However, a small proportion of patients suffer from persistent or recurrent symptoms after surgery and they are usually subsequently treated with pneumodilation (PD). Data on the efficacy of PD as secondary treatment for achalasia are scarce. Therefore, this study aimed to investigate the efficacy of PD as treatment for achalasia patients suffering from persistent or recurrent symptoms after Heller myotomy. METHODS: Patients with recurrent or persistent symptoms (Eckardt score >3) after Heller myotomy were selected. Patients were treated with PD, using a graded distension protocol with balloon sizes ranging from 30 to 40 mm. After each dilation symptoms were assessed to evaluate whether a subsequent dilation with a larger balloon size was required. Patients with recurrent or persistent symptoms (Eckardt score >3) after treatment with a 40-mm balloon were identified as failures. KEY RESULTS: Twenty-four patients were included in total; 15 patients with achalasia type I, seven with achalasia type II and two with achalasia type III. Median relapse time was 2.5 years after Heller myotomy (IQR: 9 years and 3 months). Three patients were not suitable for PD; one patient was morbidly obese and not fit for any form of sedation and two had a siphon-shaped esophagus leaving 21 patients to treat. Eight patients were successfully treated with a single 30-mm balloon dilation (median follow-up time: 6.5 years; IQR: 7.5 years). Four patients required dilations with 30- and 35-mm balloons (median follow-up time: 11 years; IQR: 3 years). Nine patients failed on the 35-mm balloon dilation and underwent a subsequent dilation with a 40-mm balloon, and all failed on this balloon as well. Thus, PD was successful in 12 of the 21 treatable patients, resulting in a success rate of 57% for treatable patients or 50% for all patients. Baseline Eckardt scores were also higher in those that failed (median: 8; IQR: 2) than those that were treated successfully (median: 5.5; IQR: 2) treated (p = 0.009). Furthermore, baseline barium column height at 5 min was higher in patients with failed (median: 6 cm; IQR: 6 cm) treatment than in patients with successful (median: 2.6 cm; IQR: 4.7 cm) treatment (p = 0.016). Baseline lower esophageal sphincter pressure was not different between patients who were treated successfully (median: 11 mmHg; IQR: 5 mmHg) and those that failed on PD (median: 17.5 mmHg; IQR: 10.8 mmHg) treatment (p > 0.05). Baseline symptom pattern was also not a predictor of successful treatment. No adverse events were recorded during or after PD. CONCLUSIONS & INFERENCES: Pneumodilation for recurrent symptoms after previous Heller myotomy is safe and has a modest success rate of 57%, using 30- and 35-mm balloons. Patients with recurrent symptoms after PD with 35-mm balloon are likely to also fail after subsequent dilation with a 40-mm balloon. PMID- 27401050 TI - Serum Levels of Albumin-beta-Amyloid Complex in Patients with Depression. AB - OBJECTIVE: Epidemiologic studies have demonstrated that suffering from depression may be a risk for Alzheimer disease (AD). As a possible biologic mechanism underlying the transition from depression to AD, it has been speculated that pathologic changes in beta-amyloid (Abeta) metabolism are involved. To further understand the peripheral kinetics of amyloid in patients with depression, we investigated serum levels of free Abeta and albumin-bound Abeta. METHODS: Seventy inpatients with DSM-IV major depressive disorder (MDD) and 81 healthy individuals (the comparison group) were recruited between June 2012 and February 2014. Serum Abeta40 and Abeta42 levels, Abeta40/Abeta42 ratio, and serum levels of albumin Abeta complexes (SLAACs) were compared between the comparison group and patients in two age groups comprising younger (<60 years) and elderly (>=60 years) people. RESULTS: SLAAC was decreased in older patients with MDD but not in younger patients. The serum-free Abeta40/Abeta42 ratio was higher in patients with depression, even in younger patients. CONCLUSION: Our findings suggest that free Abeta and the albumin-bound Abeta reflect a different serum amyloid kinetics in depression. We speculate that serum-free Abeta reflects changes in amyloid metabolism in patients suffering from depression and albumin-bound Abeta reflects AD pathology and may be a potential predictor of the prodromal stage of AD. PMID- 27401051 TI - Peer Review at the American Journal of Geriatric Psychiatry-An Appeal to the Better Angels of Our Nature. PMID- 27401052 TI - Short-Term Effects of a Gain-Focused Reappraisal Intervention for Dementia Caregivers: A Double-Blind Cluster-Randomized Controlled Trial. AB - OBJECTIVE: To examine the effects of a benefit-finding intervention, the key feature being the use of gain-focused reappraisal strategies to find positive meanings and benefits in caring for someone with dementia. METHODS: In a cluster randomized, double-blind, controlled trial conducted in social centers and clinics, 129 caregivers aged 18 + and without cognitive impairment, providing at least 14 care hours per week to a relative with mild-to-moderate Alzheimer disease, and scoring >= 3 on the Hamilton Depression Rating Scale were studied. Exclusion criterion was care recipient having parkinsonism or other forms of dementia. The benefit-finding intervention was evaluated against two treatment-as usuals, namely, simplified psychoeducation (lectures only) and standard psychoeducation. Each intervention lasted 8 weeks, with a 2-hour session per week. Randomization into these conditions was based on center/clinic membership. Primary outcome was depressive symptom. Secondary outcomes were Zarit Burden Interview, role overload, and psychological well-being. Self-efficacy beliefs and positive gains were treated as mediators. Measures were collected at baseline and post-treatment. RESULTS: Regression analyses showed benefit-finding treatment effects on all outcomes when compared with simplified psychoeducation and effects on depressive symptoms and Zarit burden when compared with standard psychoeducation. Effect sizes were medium-to-large for depressive symptoms (d = 0.77 to -0.96) and medium for secondary outcomes (d = |0.42-0.65|). Furthermore, using the bootstrapping method, we found significant mediating effects by self efficacy in controlling upsetting thoughts and positive gains, with the former being the primary mediator. CONCLUSION: Finding positive gains reduces depressive symptoms and burden and promotespsychological well-being primarily through enhancing self-efficacy in controlling upsetting thoughts. PMID- 27401053 TI - An efficient and sustainable synthesis of NHC gold complexes. AB - A simple, efficient and sustainable method for the general synthesis of NHC gold(i) complexes is described. The reaction of imidazolium salts, of different electronic and steric requirements, with [AuX(tht)] (tht = tetrahydrothiophene) derivatives, in the presence of NBu4(acac), in air and at room temperature leads to the NHC gold species in good yields and with very short reaction times. PMID- 27401054 TI - Direct Synthesis of alpha-Allenols from TMS-Protected Alkynes and Aldehydes Mediated by Tetrabutylammonium Fluoride. AB - A unique chemoselective synthesis of alpha-allenic alcohols is presented. Tetrabutylammonium fluoride (TBAF) mediated this transformation under mild reaction conditions. A range of functional groups is well-tolerated in this reaction, while affording adducts in moderate to excellent yields (48-96 %, average 76 %). Mechanistic studies, including the use of tetrabutylammonium hydroxide (TBAH), revealed that the hydroxide ion can be the responsible for the observed rearrangement. PMID- 27401055 TI - Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights. AB - Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory system. It is generally chronic and challenging to treat. The recommended pharmacotherapy for neuropathic pain includes the use of some antidepressants, such as tricyclic antidepressants (TCAs) (amitriptyline...) or serotonin and noradrenaline re-uptake inhibitors (duloxetine...), and/or anticonvulsants such as the gabapentinoids gabapentin or pregabalin. Antidepressant drugs are not acute analgesics but require a chronic treatment to relieve neuropathic pain, which suggests the recruitment of secondary downstream mechanisms as well as long-term molecular and neuronal plasticity. Noradrenaline is a major actor for the action of antidepressant drugs in a neuropathic pain context. Mechanistic hypotheses have implied the recruitment of noradrenergic descending pathways as well as the peripheral recruitment of noradrenaline from sympathetic fibers sprouting into dorsal root ganglia; and importance of both alpha2 and beta2 adrenoceptors have been reported. These monoamine re-uptake inhibitors may also indirectly act as anti-proinflammatory cytokine drugs; and their therapeutic action requires the opioid system, particularly the mu (MOP) and/or delta (DOP) opioid receptors. Gabapentinoids, which target the voltage dependent calcium channels alpha2delta-1 subunit, inhibit calcium currents, thus decreasing the excitatory transmitter release and spinal sensitization. Gabapentinoids also activate the descending noradrenergic pain inhibitory system coupled to spinal alpha2 adrenoceptors. Gabapentinoid treatment may also indirectly impact on neuroimmune actors, like proinflammatory cytokines. These drugs are effective against neuropathic pain both with acute administration at high dose and with repeated administration. This review focuses on mechanistic knowledge concerning chronic antidepressant treatment and gabapentinoid treatment in a neuropathic pain context. PMID- 27401056 TI - Metastasis suppressor 1 regulates neurite outgrowth in primary neuron cultures. AB - Metastasis suppressor 1 (MTSS1) or missing in metastasis (MIM) is an actin- and membrane-binding protein with tumor suppressor functions. MTSS1 is important for cell morphology, motility, metastasis. The role of MTSS1 in cell morphology has been widely investigated in non-neuronal tissues; however the role of MTSS1 in neurite outgrowth remains unclear. Here we investigated the effect of MTSS1 on neurite outgrowth in primary cerebellar granule and hippocampal neurons of mouse. We found that overexpression of MTSS1 in cerebellar granule neurons significantly enhanced dendrite elaboration but inhibited axon elongation. This phenotype was significantly reduced by deletion of the Wiskott-Aldrich homology 2 (WH2) motif and point mutation in the insulin receptor substrate p53 (IRSp53) and MIM/MTSS1 homology (IMD) domain. Furthermore, inhibition of Rac1 activity or blocking of phosphatidyl inositol phosphates (PIPs) signaling decreased the effect of MTSS1 markedly. In accordance with the over-expression data, knockdown of MTSS1 in cerebellar granule neurons could increase the axon length but decrease the dendrite length and the number of dendrites. In addition, MTSS1 knock down in embryonic hippocampal neurons suppressed neurite branching and reduced dendrite length. Our findings have demonstrated that MTSS1 modulates neuronal morphology, possibly through a Rac1-PIPs signaling pathway. PMID- 27401057 TI - Molecular Study of Dirofilaria immitis and Dirofilaria repens in Dogs from Tunisia. AB - Dirofilaria immitis and Dirofilaria repens are mosquito-borne nematodes which infect primarily dogs as their main definitive hosts. They cause cardiopulmonary (D. immitis) or cutaneous (D. repens) dirofilariasis in canids and other carnivores and can accidentally be transmitted to humans where they can induce a variety of clinical outcomes depending on organ localization. Dirofilaria spp. infection in dogs was assessed using molecular methods (PCR and sequencing) to identify the different Dirofilaria species occurring in 200 dogs from Northern and Central Tunisia. The overall molecular prevalence of Dirofilaria spp. was 17.5% (35/200). The prevalence of D. immitis (14.5%) was significantly higher than for D. repens (3%). Molecular prevalence of D. immitis was significantly higher in suburban compared to urban and rural regions. There was no difference in molecular prevalence of D. immitis or D. repens according to the dogs' (sex or use). Dirofilaria immitis amplicons (accession numbers KR676386) fall into the same clade with D. immitis from China, India and Taiwan. Comparison of the partial sequences of D. repensITS2 rDNA gene (KR676387) revealed 99.6% similarity with D. repens reported in dogs from USA. It had also 97.6% similarity with D. repens from mosquitoes in Czech Republic. High dog parasite burdens should motivate both medical doctors and veterinarians to consider these frequent infections. PMID- 27401060 TI - Obsessive compulsive and related disorders: comparing DSM-5 and ICD-11. AB - Obsessive-compulsive disorder (OCD) has been recognized as mainly characterized by compulsivity rather than anxiety and, therefore, was removed from the anxiety disorders chapter and given its own in both the American Psychiatric Association (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the Beta Draft Version of the 11th revision of the World Health Organization (WHO) International Classification of Diseases (ICD-11). This revised clustering is based on increasing evidence of common affected neurocircuits between disorders, differently from previous classification systems based on interrater agreement. In this article, we focus on the classification of obsessive-compulsive and related disorders (OCRDs), examining the differences in approach adopted by these 2 nosological systems, with particular attention to the proposed changes in the forthcoming ICD-11. At this stage, notable differences in the ICD classification are emerging from the previous revision, apparently converging toward a reformulation of OCRDs that is closer to the DSM-5. PMID- 27401059 TI - Development of the photosynthetic apparatus of Cunninghamia lanceolata in light and darkness. AB - Here, we compared the development of dark- and light-grown Chinese fir (Cunninghamia lanceolata) cotyledons, which synthesize chlorophyll in the dark, representing a different phenomenon from angiosperm model plants. We determined that the grana lamellar membranes were well developed in both chloroplasts and etiochloroplasts. The accumulation of thylakoid membrane protein complexes was similar between chloroplasts and etiochloroplasts. Measurement of chlorophyll fluorescence parameters indicated that photosystem II (PSII) had low photosynthetic activities, whereas the photosystem I (PSI)-driven cyclic electron flow (CEF) rate exceeded the rate of PSII-mediated photon harvesting in etiochloroplasts. Analysis of the protein contents in etiochloroplasts indicated that the light-harvesting complex II remained mostly in its monomeric conformation. The ferredoxin NADP+ oxidoreductase and NADH dehydrogenase-like complexes were relatively abundantly expressed in etiochloroplasts for Chinese fir. Our transcriptome analysis contributes a global expression database for Chinese fir cotyledons, providing background information on the regulatory mechanisms of different genes involved in the development of dark- and light grown cotyledons. In conclusion, we provide a novel description of the early developmental status of the light-dependent and light-independent photosynthetic apparatuses in gymnosperms. PMID- 27401058 TI - The mixed-lineage kinase 3 inhibitor URMC-099 facilitates microglial amyloid-beta degradation. AB - BACKGROUND: Amyloid-beta (Abeta)-stimulated microglial inflammatory responses engage mitogen-activated protein kinase (MAPK) pathways in Alzheimer's disease (AD). Mixed-lineage kinases (MLKs) regulate upstream MAPK signaling that include p38 MAPK and c-Jun amino-terminal kinase (JNK). However, whether MLK-MAPK pathways affect Abeta-mediated neuroinflammation is unknown. To this end, we investigated if URMC-099, a brain-penetrant small-molecule MLK type 3 inhibitor, can modulate Abeta trafficking and processing required for generating AD associated microglial inflammatory responses. METHODS: Abeta1-42 (Abeta42) and/or URMC-099-treated murine microglia were investigated for phosphorylated mitogen activated protein kinase kinase (MKK)3, MKK4 (p-MKK3, p-MKK4), p38 (p-p38), and JNK (p-JNK). These pathways were studied in tandem with the expression of the pro inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. Gene expression of the anti-inflammatory cytokines, IL-4 and IL-13, was evaluated by real-time quantitative polymerase chain reaction. Abeta uptake and expression of scavenger receptors were measured. Protein trafficking was assessed by measures of endolysosomal markers using confocal microscopy. RESULTS: Abeta42-mediated microglial activation pathways were shown by phosphorylation of MKK3, MKK4, p38, and JNK and by expression of IL-1beta, IL-6, and TNF-alpha. URMC 099 modulated microglial inflammatory responses with induction of IL-4 and IL-13. Phagocytosis of Abeta42 was facilitated by URMC-099 with up-regulation of scavenger receptors. Co-localization of Abeta and endolysosomal markers associated with enhanced Abeta42 degradation was observed. CONCLUSIONS: URMC-099 reduced microglial inflammatory responses and facilitated phagolysosomal trafficking with associated Abeta degradation. These data demonstrate a new immunomodulatory role for URMC-099 to inhibit MLK and to induce microglial anti inflammatory responses. Thus, URMC-099 may be developed further as a novel disease-modifying AD therapy. PMID- 27401061 TI - Associations of TNF-alpha and IL-6 polymorphisms with osteoporosis through joint effects and interactions with LEPR gene in Taiwan: Taichung Community Health Study for Elders (TCHS-E). AB - Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-alpha. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-alpha, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-alpha and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-alpha; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-alpha and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95 % CI 1.61-13.40, p = 0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p < 0.05 for interaction between physical activity and LEPR rs1751492). In men, we detected significant interactions of IL-6 rs1800796 with LEPR rs1805096 and rs1892534 for FN and TH OST (all p < 0.05). Our data indicate that LEPR gene may play joint and interactive roles with TNF-alpha and IL-6 genes and physical inactivity in development of OST. Haplotype analyses revealed that the correlations tended to be prominent in men with FN OST. PMID- 27401063 TI - Developing sustainable social programmes for rural ethnic seniors: perspectives of community stakeholders. AB - This qualitative study explores barriers to delivering sustainable rural community programmes to increase social participation among Australian ethnic seniors. In 2013, in-depth interviews were conducted with 14 stakeholders across eight rural/regional organisations that had received state government funding to provide social participation initiatives for ethnic seniors. Within interviews, participants were asked to outline factors that had enhanced or hindered their capacity to deliver the funded projects, and their plans for sustainability. Data were analysed thematically in accordance with Shediac-Rizkallah and Bone's (1998) tripartite programme sustainability framework (project design and implementation, organisational setting and broader community environment). Findings indicate that in the context of resource and staffing constraints and a lack of ethnic critical mass, programme sustainability reflected the increased capacity of rural ethnic seniors to integrate into existing community groups and maintain their own groups and activities. However, this is dependent on the ability of mainstream government, health and social care services to cater for diverse cultural needs and preferences, the ability of rural organisations to support ethnic seniors to manage their own cultural groups and activities, and the capacity of funding bodies, rural community and policy structures to maintain cultural sensitivity while compensating for the rural premium. In addition to identifying some key learnings for rural governments, health and community organisations, this research highlights the precarious nature of rural programme sustainability for ethnic seniors in the context of wider community, organisational and policy constraints. PMID- 27401062 TI - Phenotype transformation of immortalized NCM460 colon epithelial cell line by TGF beta1 is associated with chromosome instability. AB - Transforming growth factor-beta1 (TGF-beta1) within tumor microenvironment has a pivotal function in cancer initiation and tumorigenesis, and hence this study was to observe the malignant transformation induced by TGF-beta1 in an immortalized colon epithelial cell line NCM460 for better understanding the mechanisms of colon carcinogenesis. Immortalized colon epithelial cell line NCM460 was used as the model of this study, and was treated with different concentrations of TGF beta1 for different time. Then, immunofluorescence was performed to observe the change of phenotype hallmarks including adherent junction protein E-cadherin, cytoskeleton protein vimentin, and tight junction marker ZO-1, western blotting analysis was performed to detect the expression of the above three markers and two transcription factors (Snail and Slug) involved in the transformation by TGF beta1. In addition, chromosome instability (CHI) including analysis of DNA-ploid was detected by flow cytometry. Our results revealed significant loss or reduction of ZO-1 and E-cadherin, and robust emergence of vimentin in the cell line NCM460 after a 15-, 20-, and 25-day treatment with 10 ng/ml TGF-beta1. Interestingly, 20 and 25 days after stimulation with 5 ng/ml TGF-beta1, expression of E-cadherin and ZO-1 revealed a pattern roughly similar to that of 10 ng/ml TGF-beta1, especially, both expressions was vanished and vimentin expression was dramatically increased at days 25 after TGF-beta1 stimulation. After a stimulation with 10 ng/ml TGF-beta1 for 15, 20, and 25 days, the levels of Snail and Slug expression in the cells were significantly up-regulated, compared with the cells treated with TGF-beta1 inhibitor LY364947, PBS or balnk control (P < 0.01). Our results found that many abnormal mitotic patterns including lagging chromosomes and anaphase bridges in NCM460 cells were induced by TGF-beta1 after its stimulation for 15, 20, and 25 days. Very few mitotic cells with treatment of PBS for 15, 20 and 25 days were non-diploid whose DNA content was greater or less than 4 N, but these cells were significantly increased after exposure to TGF-beta1 for 15, 20, and 25 days, which was associated with the induction of hypo-diploid, hyper-diploid, and poly-diploid (P < 0.05).These data indicate that TGF-beta1 induces a phenotypic transformation of normal colon epithelium similar to its pro-tumoral behaviors in TME, involving in alteration of chromosome stability. PMID- 27401064 TI - Multitarget Therapeutic Effect of Fasudil in APP/PS1transgenic Mice. AB - INTRODUCTION: Therapeutic strategies targeting Alzheimer's disease-related molecule beta- amyloid (Abeta), Tau protein and beta-site amyloid precursor protein cleaving enzyme (BACE) have been recently explored. However, the treatment effect for single target is not ideal. Based on multiaspect roles of Rho kinase inhibitor Fasudil on neuroprotection, neurorepair and immunomodulation, we observed therapeutic potential of Fasudil and explored possible mechanisms in amyloid precursor protein/ presenilin-1 transgenic (APP/PS1 Tg) mice, an animal model of Alzheimer's disease. METHODS: APP/PS1 Tg mice were treated with Fasudil (25 mg/kg/day) for 2 months by intraperitoneal injection. Mouse behavior tests were recorded every day. The expression of Abeta deposition, Tau protein phosphorylation, BACE and postsynaptic density 95 (PSD 95) in hippocampus was assayed. The levels in the brain of Toll-like receptors (TLRs)-nuclear factor kappa B/p65(NF-kappaB/p65)- myeloid differentiation primary response gene 88 (MyD88) inflammatory cytokine axis were measured. RESULTS: Fasudil treatment ameliorated learning and memory deficits, accompanied by reduced Abeta deposition, Tau protein phosphorylation, and BACE expression, as well as increased PSD-95 expression in hippocampus. Fasudil intervention also inhibited TLR-2/4, p-NF-kappaB/p65, MyD88, interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha for TLRs-NF-kappaB-MyD88 inflammatory cytokine axis and the induction of interleukin-10. CONCLUSION: Fasudil exhibited multitarget therapeutic effect in APP/PS1 Tg mice. The study provides preclinical evidence that Fasudil treatment ameliorated memory deficits in APP/PS1 Tg mice, accompanied by the reduction of Abeta deposition and Tau protein phosphorylation, the decrease of BACE and the increase of PSD-95, as well as inhibition of TLRs-NF kappaB-MyD88 inflammatory cytokine axis. However, these results still need to be repeated and confirmed before clinical application. PMID- 27401065 TI - The Protective Effect of Jatrorrhizine Against Oxidative Stress in Primary Rat Cortical Neurons. AB - OBJECTIVES: This study investigated the neuroprotective effects of Jatrorrhizine in rat cortical neurons. METHOD: The effects of Jatrorrhizine on hydrogen peroxide (H2O2)-induced cell lesion, levels of lipid peroxidation and antioxidant enzyme activities were investigated in rat cortical neurons. Levels of mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were measured by fluorescent rhodamine staining and 2',7' dichlorfluorescein-diacetate staining, respectively. ATP content was measured by a high performance liquid chromatography. The protein levels for Bax, Bcl2 and cleaved caspase-3 were analyzed by western blot protein expression. RESULTS: There was a significant reduction in cell viability and activities of Superoxide dismutase and glutathione peroxidase for the cortical neurons after exposure to 50MUM H2O2 for 12h. The hydrogen peroxide increased the production of malondialdehyde and ROS but decreased MMP and ATP in the neurons. However, pretreatment with different concentrations of Jatrorrhizine (5-20MUM) inhibited H2O2-induced neurotoxicity markedly. Jatrorrhizine also attenuated the H2O2 induced Bcl-2/Bax ratio reduction and caspase-3 activation in these neurons. CONCLUSIONS: Our findings suggest that Jatrorrhizine plays a critical neuroprotective role in H2O2 - induced apoptosis through its anti-oxidative actions. This may allow Jatrorrhizine to be a novel therapeutic with its high bioavailability to treat Alzheimer's disease. PMID- 27401067 TI - Validation of the Rational and Experiential Multimodal Inventory in the Italian Context. AB - The unfavorable relations of the Rational and Experiential Inventory Experiential scale with objective criterion measures and its limited content validity led Norris and Epstein to propose a more content-valid measure of the experiential thinking style, the Rational and Experiential Multimodal Inventory (REIm), in order to assess the several facets of a broader experiential system consisting of interrelated components. This study aimed to provide the Italian validation of the inventory by examining its psychometric features, its factor structure (Study 1, N = 545), and its convergent and discriminant validity (Study 2, N = 257). Study 1 supported the 2- and 4-factor solutions, and multi-group analyses confirmed the invariance measurement across age and gender for both models. Study 2 provided evidence for both the convergent validity by supporting the theoretical associations among Rational and Experiential Multimodal Inventory scores and similar and related measures, and the discriminant validity by showing associations between the two thinking styles and a different but conceptually related construct, i.e., identity formation. No associations between Rational and Experiential Multimodal Inventory scores and social desirability were found. The Italian version of the Rational and Experiential Multimodal Inventory showed satisfactory psychometric properties, thus confirming its validity. PMID- 27401068 TI - Transgenerational Authenticity Measurement: A Comment on Ito et al. (2009). AB - The authors examined their previously published studies of transgenerational authenticity in a Japanese cohort (Ito, Horikoshi, & Kodama). In the previous paper, the authors addressed semantic and semiotic concerns. In this paper, design flaws and statistical flaws are examined. PMID- 27401069 TI - An English Word Database of EMOtional TErms (EMOTE). AB - Research in the socio-emotional domain may require words for experimental settings rated on emotionally and socially relevant word characteristics (e.g., valence and desirability). In addition, cognitively relevant word characteristics (e.g., imagery) are important for research in the interface of emotion and cognition (e.g., emotional memory). To provide researchers with a corresponding word pool, the database of English EMOtional TErms (EMOTE) provides subjective ratings for 1287 nouns and 985 adjectives. Nouns and adjectives were rated on valence, arousal, emotionality, concreteness, imagery, familiarity, and clarity of meaning. In addition, adjectives were rated on control, desirability, and likeableness. EMOTE norms provide an easily accessible word pool for research in the socio-emotional domain. To illustrate the usefulness of this database, norms were linked to memorability scores from a word recognition task for EMOTE nouns. The database as well as future directions are discussed. PMID- 27401066 TI - Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation. AB - BACKGROUND: The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking. METHODS: To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns. RESULTS: Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. CONCLUSIONS: Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic targets for the treatment of various cancers. PMID- 27401070 TI - The BMJ appoints two new ethics committee members. PMID- 27401071 TI - Pulmonary valve replacement in older children and adults using stented bioprostheses. AB - More than 50% of children who undergo repair of tetralogy of Fallot (TOF) using a transannular patch will require pulmonary valve replacement (PVR) in early adulthood. The premise of PVR in this setting is to ameliorate the relentless right ventricular (RV) dilatation that otherwise occurs in the presence of severe pulmonary regurgitation. Severe RV dilatation is associated with RV dysfunction, symptoms of exercise intolerance, tricuspid regurgitation and-occasionally-life threatening RV failure or dangerous ventricular tachyarrhythmia. Increasingly, patients referred for PVR are asymptomatic young adults with busy lives and dependants. Redo cardiac surgery in this setting is high-stakes surgery. Here, we outline the surgical approach taken in a centre with a history of >1000 such operations. PMID- 27401072 TI - Transaortic transcatheter aortic valve replacement through a right minithoracotomy with the balloon-expandable Sapien 3 valve. AB - Transaortic transcatheter aortic valve replacement performed through a right anterolateral minithoracotomy at the second intercostal space is a safe and standardized minimally invasive procedure carrying important clinical advantages for the patient, in particular, no damage to the ventricular apex, preservation of the diseased peripheral arteries and no cross of the aortic arch with the delivery system, meaning a lower risk of calcium dislodgement and neurological complications. Using the third-generation, balloon-expandable Edwards SapienTM 3 transcatheter heart valve and the CertitudeTM delivery system, the transaortic procedure is easily performed under fluoroscopic and echocardiographic guidance. Compared with the transapical procedure, the transaortic technique requires an inversely mounted stent valve and follows the standard guidelines for valve positioning and deployment under rapid pacing. The transaortic approach through a right anterolateral minithoracotomy at the second intercostal space combines the positive aspects of both transfemoral and transapical valve replacements without the risks of either procedure (left ventricular, coronary and peripheral vascular injuries). PMID- 27401073 TI - Spinal disease in myeloma: cohort analysis at a specialist spinal surgery centre indicates benefit of early surgical augmentation or bracing. AB - BACKGROUND: Multiple myeloma osteolytic disease affecting the spine results in vertebral compression fractures. These are painful, result in kyphosis, and impact respiratory function and quality of life. We explore the impact of time to presentation on the efficacy of spinal treatment modalities. METHODS: We retrospectively reviewed 183 patients with spinal myeloma presenting to our service over a 2 year period. RESULTS: Median time from multiple myeloma diagnosis to presentation at our centre was 195 days. Eighty-four patients (45.9 %) were treated with balloon kyphoplasty and the remainder with a thoracolumbar sacral orthosis as per our published protocol. Patients presenting earlier than 195 days from diagnosis had significant improvements in patient reported outcome measures: EuroQol 5-Dimensions (p < 0.001), Oswestry Disability Index (p < 0.001), and Visual Analogue Pain Score (p < 0.001) at follow-up, regardless of treatment. Patients presenting after 195 days, however, only experienced benefit following balloon kyphoplasty, with no significant benefit from non-operative management. CONCLUSION: Vertebral augmentation and thoracolumbar bracing improve patient reported outcome scores in patients with spinal myeloma. However, delay in treatment negatively impacts clinical outcome, particularly if managed non operatively. It is important to screen and treat patients with MM and back pain early to prevent deformity and improve quality of life. PMID- 27401074 TI - Up-regulation of MCM3 Relates to Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats. AB - Minichromosome maintenance complex component 3, one of the minichromosome maintenance proteins, functions as a part of pre-replication complex to initiate DNA replication in eukaryotes. Minichromosome maintenance complex component 3 (MCM3) was mainly implied in cell proliferation and tumorigenesis. In addition, MCM3 might play an important role in neuronal apoptosis. However, the functions of MCM3 in central nervous system are still with limited acquaintance. In this study, we performed a traumatic brain injury (TBI) model in adult rats. Western blot and immunohistochemistry staining showed up-regulation of MCM3 in the peritrauma brain cortex. The expression patterns of active caspase-3 and Bax, Bcl 2 were parallel with that of MCM3. Immunofluorescent staining and terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling suggested that MCM3 was involved in neuronal apoptosis. In conclusion, our data indicated that MCM3 might play an important role in neuronal apoptosis following TBI. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against TBI. PMID- 27401075 TI - Parameterizing developmental changes in epistemic trust. AB - Children rely on others for much of what they learn, and therefore must track who to trust for information. Researchers have debated whether to interpret children's behavior as inferences about informants' knowledgeability only or as inferences about both knowledgeability and intent. We introduce a novel framework for integrating results across heterogeneous ages and methods. The framework allows application of a recent computational model to a set of results that span ages 8 months to adulthood and a variety of methods. The results show strong fits to specific findings in the literature trust, and correctly fails to fit one representative result from an adjacent literature. In the aggregate, the results show a clear development in children's reasoning about informants' intent and no appreciable changes in reasoning about informants' knowledgeability, confirming previous results. The results extend previous findings by modeling development over a much wider age range and identifying and explaining differences across methods. PMID- 27401076 TI - Dual Roles for Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) in Cancer Progression. AB - Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) are members of the hnRNP family of RNA binding proteins that regulate alternative splicing events associated with epithelial phenotypes. These proteins play crucial roles during organogenesis, including craniofacial and epidermal development as well as branching morphogenesis in the lungs and salivary glands. Recent reports have also addressed their roles during cancer progression. Expression of ESRP proteins is low in normal epithelium but upregulated in carcinoma in situ and advanced carcinomas. Intriguingly, they are downregulated in invasive fronts. The plastic nature of ESRP expression suggests dual roles for them in cancer progression. Consistently, it has been shown that ESRPs suppress motility and anchorage independent growth of cancer cells while supporting cell survival by enhancing resistance to reactive oxygen species. Regulatory circuits that fine-tune ESRP gene expression have recently emerged. Here, we summarize recent findings on the molecular mechanisms by which ESRPs exert positive as well as negative effects on cancer progression. PMID- 27401077 TI - Improving the Bacterial Recovery by Using Dithiothreitol with Aerobic and Anaerobic Broth in Biofilm-Related Prosthetic and Joint Infections. AB - Biofilm-related infections are serious complications in the orthopaedic prosthetic field and an accurate, quick microbiological diagnosis is required to set up a specific antimicrobial therapy. It is well known that the diagnosis of these infections remains difficult due to the bacterial embedding within the biofilm matrix on the implant surfaces. Recently, the use of DL-dithiothreitol (DTT) has been proved effective in biofilm detachment from orthopaedic devices.The purpose of the study is to evaluate the efficacy of two DTT solutions enriched with specific broths for aerobic or anaerobic bacteria to dislodge pathogens from the biofilm, while supporting the bacterial recovery and viability. To do this, different experimental solutions were tested for efficacy and stability on strong biofilm producers: S. aureus and P. acnes. Mainly, we evaluate the capability of DTT dissolved in saline solution, brain heart infusion or thioglycollate broth to support the bacterial detachment from prosthetic materials and bacterial growth at different time points and storage conditions.We demonstrated that the use of DTT enriched with specific bacterial broths could be a suitable approach to optimize the bacterial detachment, recovery, growth and viability in the diagnosis of biofilm-related infections developed on orthopaedic prosthetic devices. PMID- 27401081 TI - Erratum to: Prospective Comparison between two different magnetic resonance defecography techniques for evaluating pelvic floor disorders: air-balloon versus gel for rectal filling. PMID- 27401082 TI - Flash Burns While on Home Oxygen Therapy: Tracking Trends and Identifying Areas for Improvement. AB - The objective was to analyze reported flash burns experienced by patients on home oxygen therapy (HOT) in the Veterans Health Administration (VHA) using a qualitative, retrospective review of VHA root cause analysis reports between January 2009 and November 2015. Of 123 cases of reported adverse events related to flash burns, 100 cases (81%) resulted in injury, and 23 (19%) resulted in death. Although 89% of veterans claimed to have quit smoking (n = 109), 92% (n = 113) of burns occurred as a result of smoking. The most common root cause was risk identification issues. Recommended actions were standardized risk assessment policies, patient education, and the adoption of fire stop valves. Patients with a history of smoking who are on HOT should be considered for fire stop valves and offered consistent counseling and follow-up using a combination of harm reduction and shared decision-making techniques. Standardization of risk identification and documentation is recommended. PMID- 27401083 TI - Aortic cross-clamping phase of cardiopulmonary bypass is related to decreased microvascular reactivity after short-term ischaemia of the thenar muscle both under intravenous and volatile anaesthesia: a randomized trial. AB - OBJECTIVES: The purpose of the present study was to assess, by near-infrared spectroscopy with an INVOS oximeter during the vascular occlusion test (VOT), the influence of cardiopulmonary bypass (CPB) on tissue saturation in the thenar muscle. The secondary aim was to compare the effects of propofol and sevoflurane anaesthesia on tissue saturation. METHODS: This was a prospective, randomized, open-label study. Sixty cardiac surgery patients received either propofol or sevoflurane anaesthesia. Three-minute VOT was performed at the following time points: 30 min after anaesthesia induction, directly after sternotomy, 20 and 40 min after aortic cross-clamping, 20 min after aortic cross-clamp removal and 45 min after weaning of cardiopulmonary bypass. Group and time effects on tissue saturation were analysed with RM-ANOVA and the post hoc Tukey test. RESULTS: In both groups at baseline, the lowest and the highest tissue saturation and the rate of saturation recovery during the reperfusion phase of the vascular occlusion test were lower during aortic cross-clamping in comparison to the values before CPB. Lower nadir tissue saturation during ischaemia was observed under propofol in comparison to sevoflurane anaesthesia (P = 0.018). CONCLUSIONS: This study demonstrated that the aortic cross-clamping phase of CPB cardiac surgery is associated with lower values of tissue saturation and a decreased rate of saturation recovery under both propofol and sevoflurane anaesthesia. Aortic cross-clamp release is followed by accelerated tissue desaturation during VOT. Propofol anaesthesia for CPB cardiac surgery results in greater reduction of nadir tissue saturation during the ischaemic phase of VOT in comparison to that of sevoflurane. TRIAL REGISTRATION NUMBER: NCT02593448. PMID- 27401084 TI - In patients with resectable non-small-cell lung cancer, is video-assisted thoracoscopic segmentectomy an appropriate alternative to video-assisted thoracoscopic lobectomy? AB - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients with resectable non-small-cell lung cancer, is video-assisted thoracoscopic segmentectomy an appropriate alternative to video-assisted thoracoscopic lobectomy?' Two hundred papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In one meta-analysis identified, there was no significant difference observed between groups in overall survival (HR = 0.808, 95% CI 0.556-1.174). All other studies identified also found no significant difference in overall survival. As well, local and distant recurrence rates and disease-free survival were similar in all studies. Two studies identified a significantly greater number of lymph nodes dissected with the video-assisted thoracosopic surgery (VATS) lobectomy procedure; however, all other studies noted no significant difference. There was evidence from two studies that VATS segmentectomy is associated with a shorter length of hospital stay than lobectomy. Between both groups, there was an overall low number of postoperative complications and 30-day mortality (highest n = 2), highlighting the safety of both procedures. Three studies compared patient groups with similar tumour sizes; the average tumour size was 17 +/- 1 mm. However, in the four other observational studies, the tumour size in the VATS lobectomy group was significantly larger. From the limited evidence currently available, VATS segmentectomy appears to be a valid alternative to VATS lobectomy. The included studies were mainly retrospective observational studies, with one meta-analysis; however, there are currently two large randomized trials ongoing with results expected to be reported in 2021. PMID- 27401085 TI - Monitoring creatine and phosphocreatine by (13)C MR spectroscopic imaging during and after (13)C4 creatine loading: a feasibility study. AB - Creatine (Cr) supplementation to enhance muscle performance shows variable responses among individuals and different muscles. Direct monitoring of the supplied Cr in muscles would address these differences. In this feasibility study, we introduce in vivo 3D (13)C MR spectroscopic imaging (MRSI) of the leg with oral ingestion of (13)C4-creatine to observe simultaneously Cr and phosphocreatine (PCr) for assessing Cr uptake, turnover, and the ratio PCr over total Cr (TCr) in individual muscles. (13)C MRSI was performed of five muscles in the posterior thigh in seven subjects (two males and two females of ~20 years, one 82-year-old male, and two neuromuscular patients) with a (1)H/(13)C coil in a 3T MR system before, during and after intake of 15 % (13)C4-enriched Cr. Subjects ingested 20 g Cr/day for 4 days in four 5 g doses at equal time intervals. The PCr/TCr did not vary significantly during supplementation and was similar for all subjects and investigated muscles (average 0.71 +/- 0.07), except for the adductor magnus (0.64 +/- 0.03). The average Cr turnover rate, assessed in male muscles, was 2.1 +/- 0.7 %/day. The linear uptake rates of Cr were variable between muscles, although not significantly different. This assessment was possible in all investigated muscles of young male volunteers, but less so in muscles of the other subjects due to lower signal-to-noise ratio. Improvements for future studies are discussed. In vivo (13)C MRSI after (13)C-Cr ingestion is demonstrated for longitudinal studies of Cr uptake, turnover, and PCr/TCr ratios of individual muscles in one exam. PMID- 27401086 TI - Creatine transporter deficiency leads to increased whole body and cellular metabolism. AB - Creatine (Cr) is a guanidino compound required for rapid replenishment of ATP in cells with a high-energy demand. In humans, mutations in the Cr transporter (CRT;SLC6A8) prevent Cr entry into tissue and result in a significant intellectual impairment, epilepsy, and aphasia. The lack of Cr on both the whole body and cellular metabolism was evaluated in Crt knockout (Crt (-/y) ) mice, a high-fidelity model of human CRT deficiency. Crt (-/y) mice have reduced body mass and, however, show a twofold increase in body fat. There was increased energy expenditure in a home cage environment and during treadmill running in Crt (-/y) mice. Consistent with the increases in the whole-body metabolic function, Crt (-/y) mice show increased cellular metabolism as well. Mitochondrial respiration increased in skeletal muscle fibers and hippocampal lysates from Crt (-/y) mice. In addition, Crt (-/y) mice had increased citrate synthase activity, suggesting a higher number of mitochondria instead of an increase in mitochondrial activity. To determine if the increase in respiration was due to increased mitochondrial numbers, we measured oxygen consumption in an equal number of mitochondria from Crt (+/y) and Crt (-/y) mice. There were no changes in mitochondrial respiration when normalized to mitochondrial number, suggesting that the increase in respiration observed could be to higher mitochondrial content in Crt (-/y) mice. PMID- 27401088 TI - Synthesis and Characteristics of FePt Nanoparticle Films Under In Situ-Applied Magnetic Field. AB - In situ external magnetic field was applied during the synthesis of FePt nanoparticles via a chemical solution method. FePt nanoparticle films were prepared on Si by a drop-coating method with and without a magnetic field. Annealing at 700 degrees C in reductive atmosphere was explored to obtain ferromagnetic FePt L10 phase. The effect of in situ-applied magnetic field on the structure, morphology, and magnetic properties of FePt nanoparticle films was characterized. It is found that the applied magnetic field during the chemical synthesis of FePt nanoparticles plays a key role in the crystallinity and magnetic property of FePt nanoparticle films. As-synthesized FePt nanoparticles under the magnetic field are monodispersed and can be self-assembled over a larger area by a dropping method. The applied magnetic field during the synthesis of FePt nanoparticles not only significantly improves the nanoparticles' c-axis preferred orientation but also benefits the phase transition of FePt nanoparticles from face-centered cubic to face-centered tetragonal structure during the annealing process. The FePt nanoparticle films derived under magnetic field also show some magnetic anisotropy. PMID- 27401087 TI - Bony injuries in homicide cases (1994-2014). A retrospective study. AB - Even when human skeletal remains are found in contexts indicative of body disposal after homicide, none of the bones may manifest injuries. When skeletons are incomplete, there are two possibilities, the injured bones are missing or none were injured. This leads to the question how frequently bones are injured during homicide, where the injuries tend to be placed, and whether the frequency of injury is related to the type of homicide. To answer these questions, the postmortem reports from all autopsies performed for homicide victims at the Institute of Legal Medicine at the University Hospital in Frankfurt am Main, Germany, between 1994 and 2014, were retrospectively evaluated for bony injuries discovered during autopsy. In 90 cases, a preliminary postmortem computed tomography (pmCT) examination had been performed. The cases were categorized into the following five groups by type of fatal trauma: blunt force, sharp force, gunshot injury, strangulation, or other. In total, the postmortem reports for 897 homicides (527 male, 370 female) were evaluated. The number of victims per trauma category were sharp force, 309; blunt force, 179; gunshot injury, 242; strangulation, 92; and other, 75. Bony injuries had been reported in 70.9 % of the homicides. The "gunshot" category contained the highest proportion of victims with bony injuries (92.6 %). With 80.4 %, the second-highest proportion of victims with bony injuries was in the "blunt force" category, followed by 66.3 % of victims in the "sharp force" group. In contrast, with 53.3 %, the second lowest proportion of victims with bony injuries was in the "strangulation" category, which contained a preponderance of female victims, followed by 17.3 % of victims with bony injuries in the "other" category. Bony injuries thus occurred in the majority of homicides. Forensic osteological analysis should, therefore, always be performed on badly decomposed human remains. Where necessary, the additional use of visualization techniques, in particular, pmCT, or maceration may be considered. The absence of bony injuries does not rule out homicide; e.g., in strangulations, bony injuries are manifest in only half the victims, even when the skeleton is intact. The relevant structures are also easily lost to decomposition, scavenging, or scattering. PMID- 27401089 TI - Flexible Field Emitter for X-ray Generation by Implanting CNTs into Nickel Foil. AB - This paper reports a novel implanting micromachining technology. By using this method, for the first time, we could implant nano-scale materials into milli scale metal substrates at room temperature. Ni-based flexible carbon nanotube (CNT) field emitters were fabricated by the novel micromachining method. By embedding CNT roots into Ni foil using polymer matrix as transfer media, effective direct contact between Ni and CNTs was achieved. As a result, our novel emitter shows relatively good field emission properties such as low turn-on field and good stability. Moreover, the emitter was highly flexible with preservation of the field emission properties. The excellent field emission characteristics attributed to the direct contact and the strong interactions between CNTs and the substrate. To check the practical application of the novel emitter, a simple X ray imaging system was set up by modifying a traditional tube. The gray shadow that appears on the sensitive film after being exposed to the radiation confirms the successful generation of X-ray. PMID- 27401090 TI - PFA toolbox: a MATLAB tool for Metabolic Flux Analysis. AB - BACKGROUND: Metabolic Flux Analysis (MFA) is a methodology that has been successfully applied to estimate metabolic fluxes in living cells. However, traditional frameworks based on this approach have some limitations, particularly when measurements are scarce and imprecise. This is very common in industrial environments. The PFA Toolbox can be used to face those scenarios. RESULTS: Here we present the PFA (Possibilistic Flux Analysis) Toolbox for MATLAB, which simplifies the use of Interval and Possibilistic Metabolic Flux Analysis. The main features of the PFA Toolbox are the following: (a) It provides reliable MFA estimations in scenarios where only a few fluxes can be measured or those available are imprecise. (b) It provides tools to easily plot the results as interval estimates or flux distributions. (c) It is composed of simple functions that MATLAB users can apply in flexible ways. (d) It includes a Graphical User Interface (GUI), which provides a visual representation of the measurements and their uncertainty. (e) It can use stoichiometric models in COBRA format. In addition, the PFA Toolbox includes a User's Guide with a thorough description of its functions and several examples. CONCLUSIONS: The PFA Toolbox for MATLAB is a freely available Toolbox that is able to perform Interval and Possibilistic MFA estimations. PMID- 27401091 TI - Utility of 17-(allylamino)-17-demethoxygeldanamycin treatment for skeletal muscle injury. AB - Repeated eccentric contractions can injure skeletal muscle and result in functional deficits that take several weeks to fully recover. The 70-kDa heat shock protein (Hsp70) is a stress-inducible molecular chaperone that maintains protein quality and plays an integral role in the muscle's repair processes following injury. Here, we attempted to hasten this recovery by pharmacologically inducing Hsp70 expression in mouse skeletal muscle with 17-(allylamino)-17 demethoxygeldanamycin (17-AAG) (40 mg/kg) both prior to and throughout the first 7 days after an injurious bout of 150 maximal eccentric contractions. Hsp70 content in the injured skeletal muscle was strongly induced following the eccentric contractions and remained elevated over the next 7 days as the muscle underwent repair. Treatment with 17-AAG increased Hsp70 content ~fivefold; however, this was significantly less than that induced by the injury. Moreover, 17-AAG treatment did not recover the decrements to in vivo isometric torque production following the bout of eccentric contractions. Together, these findings demonstrate that although Hsp70 content was induced in the uninjured skeletal muscle, treatment of 17-AAG (40 mg/kg) was not a preventive measure to either reduce the severity of skeletal muscle damage or enhance functional recovery following a bout of maximal eccentric contractions. PMID- 27401092 TI - Erratum and additional analyses re: Calcium plus vitamin D supplementation and the risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. PMID- 27401093 TI - Response to comments by Moran et al. on: The effect of prolonged breast-feeding on the development of postmenopausal osteoporosis in population with insufficient calcium intake and vitamin D level. PMID- 27401094 TI - Comments on: The effect of prolonged breast-feeding on the development of postmenopausal osteoporosis in population with insufficient calcium intake and vitamin D level. PMID- 27401095 TI - Improved malaria case management in formal private sector through public private partnership in Ethiopia: retrospective descriptive study. AB - BACKGROUND: Malaria is a major public health problem and still reported among the 10 top causes of morbidity and mortality in Ethiopia. More than one-third of the people sought treatment from the private health sector. Evaluating adherences of health care providers to standards are paramount importance to determine the quality and the effectiveness of service delivery. Therefore, the aim of this study was to evaluate the contribution of public private mix (PPM) approach in improving quality of malaria case management among formal private providers. METHODS: A retrospective data analysis was conducted using 2959 facility-months data collected from 110 PPM for malaria care facilities located in Amhara, Dire Dawa, Hareri, Oromia, Southern Nation Nationalities and Peoples and Tigray regions. Data abstraction formats were used to collect and collate the data on quarterly bases. The data were manually cleaned and analysed using Microsoft Office Excel 2010. To claim statistical significance non-parametric McNemar test was done and decision accepted at P < 0.05. RESULTS: From April 2012-September 2015, a total of 873,707 malaria suspected patients were identified, of which one fourth (25.6 %) were treated as malaria cases. Among malaria suspected cases the proportion of malaria investigation improved from recorded in first quarter 87.7 100.0 % in last quarter (X(2) = 66.84, P < 0.001). The majority (96.0 %) were parasitologically-confirmed cases either by using microscopy or rapid diagnostic tests. The overall slid positivity rate was 25.1 % of which half (50.7 %) were positive for Plasmodium falciparum and slightly lower than half (45.2 %) for Plasmodium vivax; the remaining 8790 (4.1 %) showed mixed infections of P. falciparum and P. vivax. Adherence to appropriate treatment using artemether lumefantrine (AL) was improved from 47.8 % in the first quarter to 95.7 % in the last quarter (X(2) = 12.89, P < 0.001). Similarly, proper patient management using chloroquine (CQ) was improved from 44.1 % in the first quarter to 98.12 % in the last quarter (X(2) = 11.62, P < 0.001). CONCLUSIONS: This study documented the chronological changes of adherence of health care providers with the national recommended standards to treat malaria. The PPM for malaria care services significantly improved the malaria case management practice of health care providers at the formal private health facilities. Therefore, regional health bureaus and partners shall closely work to scale up the initiated PPM for malaria care service. PMID- 27401097 TI - Visual detection of cortical breaks in hand joints: reliability and validity of high-resolution peripheral quantitative CT compared to microCT. AB - BACKGROUND: To study the reliability and validity of high-resolution peripheral quantitative CT (HR-pQCT) with microCT (MUCT) as gold standard in the visual detection of cortical breaks in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. METHODS: Ten cadaveric fingers (10 MCP and 9 PIP joints) were imaged by HR-pQCT and MUCT and visually analyzed by two independent readers. Intra- and interreader reliability were evaluated for the presence (yes/no, kappa statistics) and the total number (intraclass correlation coefficient, ICC) of cortical breaks. Sensitivity, specificity, positive and negative predictive value (PPV respectively NPV) of HR-pQCT in detecting cortical breaks were calculated. RESULTS: With HR-pQCT, mean 149 cortical breaks were identified and with MUCT mean 129 (p < 0.05). Intrareader reliability for the presence of a cortical break per quadrant was 0.52 (95 % CI 0.48-0.56) and 0.71 (95 % CI 0.67-0.75) for HR-pQCT and MUCT, respectively, and for the total number of cortical breaks 0.61 (95 % CI 0.49-0.70) and 0.75 (95 % CI 0.68-0.82). Interreader reliability for the presence of a cortical break per quadrant was 0.37 (95 % CI 0.33-0.41) and 0.45 (95 % CI 0.41-0.49) for HR-pQCT and MUCT, respectively, and for the number of cortical breaks 0.55 (95 % CI 0.43-0.65) and 0.54 (95 % CI 0.35-0.67). Sensitivity, specificity, PPV and NPV of HR-pQCT were 81.6, 64.0, 81.6, and 64 % respectively. CONCLUSION: Cortical breaks were commonly visualized in MCP and PIP joints with HR-pQCT and MUCT. Reliability of both HR-pQCT and MUCT was fair to moderate. HR-pQCT was highly sensitive to detect cortical breaks with MUCT as gold standard. PMID- 27401096 TI - Low-protein diets for chronic kidney disease patients: the Italian experience. AB - BACKGROUND: Nutritional treatment has always represented a major feature of CKD management. Over the decades, the use of nutritional treatment in CKD patients has been marked by several goals. The first of these include the attainment of metabolic and fluid control together with the prevention and correction of signs, symptoms and complications of advanced CKD. The aim of this first stage is the prevention of malnutrition and a delay in the commencement of dialysis. Subsequently, nutritional manipulations have also been applied in association with other therapeutic interventions in an attempt to control several cardiovascular risk factors associated with CKD and to improve the patient's overall outcome. Over time and in reference to multiple aims, the modalities of nutritional treatment have been focused not only on protein intake but also on other nutrients. DISCUSSION: This paper describes the pathophysiological basis and rationale of nutritional treatment in CKD and also provides a report on extensive experience in the field of renal diets in Italy, with special attention given to approaches in clinical practice and management. Italian nephrologists have a longstanding tradition in implementing low protein diets in the treatment of CKD patients, with the principle objective of alleviating uremic symptoms, improving nutritional status and also a possibility of slowing down the progression of CKD or delaying the start of dialysis. A renewed interest in this field is based on the aim of implementing a wider nutritional therapy other than only reducing the protein intake, paying careful attention to factors such as energy intake, the quality of proteins and phosphate and sodium intakes, making today's low-protein diet program much more ambitious than previous. The motivation was the reduction in progression of renal insufficiency through reduction of proteinuria, a better control of blood pressure values and also through correction of metabolic acidosis. One major goal of the flexible and innovative Italian approach to the low-protein diet in CKD patients is the improvement of patient adherence, a crucial factor in the successful implementation of a low-protein diet program. PMID- 27401098 TI - Fetal Alcohol Growth Restriction and Cognitive Impairment. AB - BACKGROUND: Although both fetal and long-term growth restriction are well documented in fetal alcohol spectrum disorders, effects on pattern of growth trajectory have not been characterized. Furthermore, the degree to which growth trajectories are related to fetal alcohol-related neurocognitive deficits is unknown. METHODS: Ninety-three heavy drinking pregnant women and 64 controls were recruited at initiation of prenatal care in Cape Town, South Africa. Small for gestational age (SGA) was defined as birth weight <10th percentile. Length/height, weight, and head circumference were measured at 6.5 and 12 months and 5, 9, and 13 years. Four growth trajectories were identified: SGA with long term postnatal growth restriction (length/height-for-age <10th percentile through 13 years); SGA with catch-up growth; no SGA or postnatal growth restriction; and late-onset postnatal stunting. IQ was assessed at 5 and 10 years, and learning, memory, and executive function at 10 years. RESULTS: Children born SGA with postnatal growth restriction were most heavily exposed. Exposure was intermediate for those born SGA with catch-up growth and lowest for those without prenatal or postnatal growth restriction. Effects on neurocognition were strongest in children with both prenatal and long-term growth restriction, more moderate in those with fetal growth restriction and postnatal catch-up, and weakest in those without growth restriction. CONCLUSIONS: These findings validate the use of growth restriction in the diagnosis of fetal alcohol spectrum disorders and identify growth trajectory as a biomarker of which heavily exposed children are at greatest risk for cognitive developmental deficits. PMID- 27401099 TI - Case Report of Methemoglobinemia in a Toddler Secondary to Topical Dapsone Exposure. AB - Aczone gel 5% contains dapsone and is a commonly used topical dermatologic therapy for acne in adolescents and adults. We describe the first reported pediatric case of a previously healthy girl presenting with acute onset of methemoglobinemia after exposure to her sibling's Aczone gel. The patient was successfully treated with methylene blue initially and subsequently needed an additional dose for rebound methemoglobinemia. This case demonstrates the complications of systemic absorption of dapsone in the pediatric population resulting in clinically significant methemoglobinemia from a single topical application. PMID- 27401100 TI - Potential Solutions to Electronic Cigarette Use Among Adolescents. PMID- 27401101 TI - Thumb-Sucking, Nail-Biting, and Atopic Sensitization, Asthma, and Hay Fever. AB - BACKGROUND: The hygiene hypothesis suggests that early-life exposure to microbial organisms reduces the risk of developing allergies. Thumb-sucking and nail-biting are common childhood habits that may increase microbial exposures. We tested the hypothesis that children who suck their thumbs or bite their nails have a lower risk of developing atopy, asthma, and hay fever in a population-based birth cohort followed to adulthood. METHODS: Parents reported children's thumb-sucking and nail-biting habits when their children were ages 5, 7, 9, and 11 years. Atopic sensitization was defined as a positive skin-prick test (>=2-mm weal) to >=1 common allergen at 13 and 32 years. Associations between thumb-sucking and nail-biting in childhood, and atopic sensitization, asthma, and hay fever at these ages were assessed by using logistic regression with adjustments for sex and other potential confounding factors: parental atopy, breastfeeding, pet ownership, household crowding, socioeconomic status, and parental smoking. RESULTS: Thirty-one percent of children were frequent thumb-suckers or nail biters at >=1 of the ages. These children had a lower risk of atopic sensitization at age 13 years (odds ratio 0.67, 95% confidence interval 0.48 0.92, P = .013) and age 32 years (odds ratio 0.61, 95% confidence interval 0.46 0.81, P = .001). These associations persisted when adjusted for multiple confounding factors. Children who had both habits had a lower risk of atopic sensitization than those who had only 1. No associations were found for nail biting, thumb-sucking, and asthma or hay fever at either age. CONCLUSIONS: Children who suck their thumbs or bite their nails are less likely to have atopic sensitization in childhood and adulthood. PMID- 27401102 TI - E-cigarettes, Cigarettes, and the Prevalence of Adolescent Tobacco Use. AB - BACKGROUND: Adolescent e-cigarette use has increased rapidly in recent years, but it is unclear whether e-cigarettes are merely substituting for cigarettes or whether e-cigarettes are being used by those who would not otherwise have smoked. To understand the role of e-cigarettes in overall tobacco product use, we examine prevalence rates from Southern California adolescents over 2 decades. METHODS: The Children's Health Study is a longitudinal study of cohorts reaching 12th grade in 1995, 1998, 2001, 2004, and 2014. Cohorts were enrolled from entire classrooms in schools in selected communities and followed prospectively through completion of secondary school. Analyses used data from grades 11 and 12 of each cohort (N = 5490). RESULTS: Among 12th-grade students, the combined adjusted prevalence of current cigarette or e-cigarette use in 2014 was 13.7%. This was substantially greater than the 9.0% adjusted prevalence of current cigarette use in 2004, before e-cigarettes were available (P = .003) and only slightly less than the 14.7% adjusted prevalence of smoking in 2001 (P = .54). Similar patterns were observed for prevalence rates in 11th grade, for rates of ever use, and among both male and female adolescents and both Hispanic and Non-Hispanic White adolescents. CONCLUSIONS: Smoking prevalence among Southern California adolescents has declined over 2 decades, but the high prevalence of combined e cigarette or cigarette use in 2014, compared with historical Southern California smoking prevalence, suggests that e-cigarettes are not merely substituting for cigarettes and indicates that e-cigarette use is occurring in adolescents who would not otherwise have used tobacco products. PMID- 27401103 TI - Medical ward round competence in internal medicine - an interview study towards an interprofessional development of an Entrustable Professional Activity (EPA). AB - BACKGROUND: The medical ward round is a central but complex activity that is of relevance from the first day of work. However, difficulties for young doctors have been reported. Instruction of ward round competence in medical curricula is hampered by the lack of a standardized description of the procedure. This paper aims to identify and describe physicians' tasks and relevant competences for conducting a medical ward round on the first day of professional work. METHODS: A review of recent literature revealed known important aspects of medical ward rounds. These were used for the development of a semi-structured interview schedule. Medical ward round experts working at different hospitals were interviewed. The sample consisted of 14 ward physicians (M = 8.82 years of work experience) and 12 nurses (M = 14.55 years of work experience) working in different specializations of internal medicine. All interviews were audiotaped, fully transcribed, and analyzed using an inductive-deductive coding scheme. RESULTS: Nine fields of competences with 18 related sub-competences and 62 observable tasks were identified as relevant for conducting a medical ward round. Over 70 % of the experts named communication, collaborative clinical reasoning and organization as essential competences. Deeper analysis further unveiled the importance of self-management, management of difficult situations, error management and teamwork. CONCLUSION: The study is the first to picture ward round competences and related tasks in detail and to define an EPA "Conducting an internal medicine ward round" based on systematic interprofessional expert interviews. It thus provides a basis for integration of ward round competences in the medical curricula in an evidence based manner and gives a framework for the development of instructional intervention studies and comparative studies in other medical fields. PMID- 27401104 TI - Paclitaxel causes degeneration of both central and peripheral axon branches of dorsal root ganglia in mice. AB - BACKGROUND: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies. The taxane agents, including paclitaxel (Taxol((r))), are effective chemotherapeutic drugs but cause degeneration of predominantly large myelinated afferent sensory fibers of the peripheral nervous system in humans and animal models. Dorsal root ganglia (DRG) neurons are sensory neurons that have unipolar axons each with two branches: peripheral and central. While taxane agents induce degeneration of peripheral axons, whether they also cause degeneration of central nervous system axons is not clear. Using a mouse model of paclitaxel-induced neuropathy, we investigated the effects of paclitaxel on the central branches of sensory axons. RESULTS: We observed that in the spinal cords of paclitaxel-intoxicated mice, degenerated axons were present in the dorsal columns, where the central branches of DRG axons ascend rostrally. In the peripheral nerves, degenerated myelinated fibers were present in significantly greater numbers in distal segments than in proximal segments indicating that this model exhibits the distal-to-proximal degeneration pattern generally observed in human peripheral nerve disorders. CONCLUSIONS: We conclude that paclitaxel causes degeneration of both the peripheral and central branches of DRG axons, a finding that has implications for the site and mode of action of chemotherapy agents on the nervous system. PMID- 27401106 TI - Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy. AB - Liver disease has been known for a long time to affect brain function. We now report the function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced by hepatic encephalopathy (HE) following bile duct ligation (BDL), a model of chronic liver disease. Assessment of spatial and object novelty detection memories was carried out in the non associative task. It consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Both spatial and object novelty detection memories were impaired by BDL after 4 weeks. In the BDL mice, pre-test intraperitoneal administration of naloxone (MU opioidergic receptor antagonist) at dose of 0.9mg/kg restored while sulpiride (D2 like dopamine receptor antagonist) at dose of 40mg/kg potentiated object novelty detection memory deficit. However, SCH23390 (D1-like dopamine receptor antagonist) at dose of 0.04mg/kg or sulpiride (20mg/kg) restored spatial novelty detection memory deficit. Moreover, SCH23390 or sulpiride impaired while naloxone did not alter both memories in sham-operated mice. Furthermore, subthreshold dose co-administration of dopaminergic antagonists together or each one plus naloxone did not alter both memory impairments in BDL mice, while all of three co administration groups impaired object novelty detection and co-administration of naloxone plus sulpiride impaired spatial detection memory in sham-operated mice. In conclusion, we suggest that opioidergic and dopaminergic systems through separate pathways may contribute in memory impairments induced by BDL in the non associative task. PMID- 27401105 TI - Characterization of urinary cotinine in non-smoking residents in smoke-free homes in the Korean National Environmental Health Survey (KoNEHS). AB - BACKGROUND: The objectives of this study were to determine urinary cotinine concentrations in non-smoking residents of smoke-free homes and to establish the relationship of urinary cotinine with housing type and other socio-demographic and secondhand smoke (SHS) exposure factors. METHODS: We used data from the Korean National Environmental Health Survey I (2009-2011). The study included 814 non-smoking adult residents living in apartments, attached, and detached housing. Residents who lived with smokers were excluded. Urinary cotinine concentration was used as a biomarker for SHS exposure. The factors associated with urinary cotinine levels in non-smoking residents were determined using multivariate regression analysis. RESULTS: Urinary cotinine was detected in 88 % of the 814 non-smoking residents of smoke-free homes. The urinary cotinine concentrations of residents living in attached [1.18 ng/mg creatinine (Cr)] and detached housing (1.23 ng/mg Cr) were significantly higher than those of residents who lived in apartments (0.69 ng/mg Cr). Urinary cotinine concentrations were significantly higher in residents who were men, those with a household income <=1000 USD/month, those who were former smokers with >1 year and <=1 year of not smoking, and those who experienced SHS odor every day. In the multivariate regression analysis, housing type, sex, former smoking status, and frequency of experiencing SHS odor were associated with urinary cotinine concentrations (R (2) = 0.14). CONCLUSIONS: The majority of non-smoking residents of smoke-free homes had detectable urinary cotinine. Housing type, sex, former smoking status, and frequency of experiencing SHS odor were predictors for urinary cotinine concentrations in the study participants. PMID- 27401107 TI - A tryptic hydrolysate from bovine milk alphas1-casein enhances pentobarbital induced sleep in mice via the GABAA receptor. AB - Studies have shown that enzymatic hydrolysis of casein, the primary protein component of cow's milk, produces peptides with various biological activities, and some of these peptides may have sleep-promoting effects. In the present study, we evaluated the sedative and sleep-promoting effects of bovine alphaS1 casein tryptic hydrolysate (CH), containing a decapeptide alphaS1-casein known as alpha-casozepine. CH was orally administered to ICR mice at various concentrations (75, 150, 300, or 500mg/kg). An hour after administration, assessment of its sedative (open-field and rota-rod tests) and sleep-potentiating effects (pentobarbital-induced sleeping test and EEG monitoring) were conducted. Although a trend can be observed, CH treatment did not significantly alter the spontaneous locomotor activity and motor function of mice in the open-field and rota-rod tests. On the other hand, CH (150mg/kg, respectively) enhanced the sleep induced by pentobarbital sodium in mice. It also promoted slow-wave (delta) EEG activity in rats; a pattern indicative of sleep or relaxation. These behavioral results indicate that CH has sleep-promoting effects, but no or has minimal sedative effects. To elucidate the probable mechanism behind the effects of CH, we examined its action on intracellular chloride ion influx in cultured human neuroblastoma cells. CH dose-dependently increased chloride ion influx, which was blocked by co-administration of bicuculline, a competitive GABAA receptor antagonist. Taken together, the results of the present study suggest that CH has sleep-promoting properties which are probably mediated through the GABAA receptor chloride ion channel complex. PMID- 27401108 TI - Central histaminergic transmission modulates the ethanol induced anxiolysis in mice. AB - Intrigued by the report demonstrating an increase in brain histamine levels by ethanol administration and central histamine transmission to affect the anxiety related behaviors, the present study examined the permissive role of central histaminergic transmission in the acute anxiolytic-like effect of the ethanol on elevated plus maze (EPM) in mice. Results demonstrated that prior administration of the agents that are known to enhance the brain histamine transmission, i.e. low dose of histamine (0.1MUg/mouse, i.c.v.) or histamine precursor, l-histidine (500, 1000mg/kg, i.p.) or low dose of histamine releasing agent (H3 receptor inverse agonist), thioperamide (2MUg/mouse) attenuated the acute anitanxiety-like effect of ethanol (2g/kg, i.p, 8% w/v) in mice on EPM. However, pre-treatment with the H1 receptor antagonist, cetirizine (0.1MUg/mouse, i.c.v.) or H2 receptor antagonist, ranitidine (50MUg/mouse, i.c.v.) failed to affect the attenuating effect of low dose of histamine on ethanol induced anxiolysis. On the other hand, only H1 receptor antagonist, cetirizine (0.1MUg/mouse, i.c.v.) was able to partially reverse the attenuation of ethanol induced anxiolysis by l-histidine (1000mg/kg, i.p.). Surprisingly, in mice pre-treated with the higher dose of histamine (50MUg/mouse, i.c.v.) or thioperamide (10MUg/mouse, i.c.v.), the ethanol (2g/kg, i.p.) induced antianxiety-like effect was further enhanced on EPM. Furthermore, this potentiating effect of high dose of histamine on the ethanol (2g/kg, i.p.) was exacerbated on pre-treatment with the H1 receptor antagonist, cetirizine, while H2 receptor antagonist, ranitidine completely reversed this action of high dose of histamine on ethanol. Supportive to these results, i.c.v. pre-treatment with H1 receptor agonist, FMPH (2, 6.5MUg/mouse, i.c.v.) attenuated while H2 receptor agonist, amthamine (0.1, 0.5MUg/mouse, i.c.v.) enhanced the ethanol induced anxiolysis in mice. Thus, it is reasonable to contemplate that central histaminergic transmission functions to negatively modulate the acute ethanol-induced anxiolysis probably via stimulation of postsynaptic H1 receptor and histamine might contribute to the anxiolytic action of ethanol via H2 receptor activation. PMID- 27401109 TI - A systematic review of tools for determining activity of localized scleroderma in paediatric and adult patients. AB - Localized scleroderma (LoS) is a rare inflammatory skin disorder that affects the dermis and sometimes subcutaneous tissues. LoS can have very long periods of quiescence followed by reactivation, but the progression or activity of the disease is difficult to measure. To review the measuring tools used for the evaluation of LoS activity, to choose the most appropriate technique to facilitate progress towards properly assessing the disease, a systematic review of the literature was carried out using the PubMed MEDLINE. Sixty-three studies describing groups of children, adults or both were reviewed and included in the analysis. Case reports were excluded. The analysed papers were published between June 1986 and February 2016. Data were extracted with a focus on instruments measuring the clinical signs of LoS, health-related quality of life (HRQoL), laboratory tests and imaging techniques. Perusal of the literature confirmed that clinical characteristics of the lesions were used to identify activity and scoring systems that focused on a series of signs, and were initially validated in cases of childhood-onset disease; however, there were no data concerning the adult-onset form of the disease. Adult patients with LoS scored lower on HDLQI than those with paediatric-onset LoS. No validated biological markers were available as correlative laboratory parameters of LoS activity. For infrared thermography, ultrasound and other imaging techniques, the features of active lesions were described, but were only useful with appropriate clinical correlation. Measuring tools have not been prospectively validated yet. Summarizing, scoring methods seem to provide the most adequate assessment of LoS and deserve to be further investigated. Combined imaging techniques create optimal conditions for the proper interpretation of the temperature at the skin surface, as well as the structure and vascularity of LoS lesions. Additional scores, musculoskeletal or neuroimaging techniques and laboratory parameters are needed for the specific disease subtypes to monitor extracutaneous manifestations. PMID- 27401110 TI - Relaparoscopic approach for recurrence after laparoscopic incisional hernia repair - a video vignette. PMID- 27401111 TI - Seasonal Fluctuations of Sap-Feeding Insect Species Infected by Xylella fastidiosa in Apulian Olive Groves of Southern Italy. AB - A study on seasonal abundance of Auchenorrhyncha species and their infectivity by Xylella fastidiosa in the Apulia region of Italy was conducted to identify ideal periods for monitoring and adoption of potential control measures against insect vectors. Adult populations of Auchenorrhyncha species were monitored monthly over a 2-yr period from five olive groves. A total of 15 species were captured, identified, and tested for presence of X. fastidiosa by polymerase chain reaction (PCR). For three species, Philaenus spumarius L., Neophilaenus campestris (Fallen), and Euscelis lineolatus Brulle, positive reactions to X. fastidiosa were obtained, on average, in 16.3, 15.9 and 18.4% of adult insects, respectively. Philaneous spumarius was the dominant species (39.8% of total Auchenorrhyncha captured) with the highest adult abundance in summer months. Adult P. spumarius and N. campestris were first detected between March and May in both years, and all insects tested during these periods (year 1: n = 42, year 2: n = 132) gave negative reactions to X. fastidiosa by PCR. Similarly, first adults of E. lineolatus that appeared from October to November (year 1: n = 20, year 2: n = 15) tested negative for presence of X. fastidiosa Given the lack of transstadial and transovarial transmission of X. fastidiosa and considering that P. spumarius is univoltine, control measures against nymphal stages of P. spumarius should be investigated as means of population suppression to reduce spread of X. fastidiosa in olive groves. PMID- 27401112 TI - Efficacy of Soybean's Event DAS-81419-2 Expressing Cry1F and Cry1Ac to Manage Key Tropical Lepidopteran Pests Under Field Conditions in Brazil. AB - Bacillus thuringiensis (Bt) event DAS-81419-2 (Conkesta technology) in soybean, Glycine max (L.) Merrill, expresses Cry1F and Cry1Ac proteins to provide protection from feeding by several lepidopteran pests. A total of 27 field experiments across nine locations were conducted from 2011 to 2015 in southern and central Brazil to characterize the efficacy of DAS-81419-2 soybean infested with Anticarsia gemmatalis Hubner (Lepidoptera: Erebidae), Chrysodeixis includens (Walker) (Lepidoptera: Noctuidae), Heliothis virescens (F.) (Lepidoptera: Noctuidae), and Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) during vegetative (V4) and reproductive (R2 and R4) crop developmental stages. The efficacy of DAS-81419-2 was compared to that of a non-Bt isogenic variety managed with or without applications of commercial foliar insecticides for lepidopteran control. DAS-81419-2 soybean consistently experienced defoliation levels of 0.5% or less (compared with 20.05-56.74% in the non-Bt, nonsprayed treatment) and larval survival of < 0.1% in all four species across the vegetative and reproductive plant stages evaluated. The efficacy of DAS-81419-2 was significantly higher than commercial foliar insecticides applied to the non-Bt variety. DAS-81419-2 soybeans containing two highly effective Bt proteins are expected to be a more robust IRM tool compared to single-trait Bt technologies. The consistent efficacy of DAS-81419-2 soybeans across years, locations, and crop stages suggests that it will be a valuable product for management of hard-to control key lepidopteran pests in South American soybean production. PMID- 27401114 TI - A chemical chaperone induces inhomogeneous conformational changes in flexible proteins. AB - Organic osmolytes also known as chemical chaperones are major cellular compounds that favor, by an unclear mechanism, protein's compaction and stabilization of the native state. Here, we have examined the chaperone effect of the naturally occurring trimethylamine N-oxide (TMAO) osmolyte on a loosely packed protein (LPP), known to be a highly flexible form, using an apoprotein mutant of the flavin-dependent RNA methyltransferase as a model. Thermal and chemical denaturation experiments showed that TMAO stabilizes the structural integrity of the apoprotein dramatically. The denaturation reaction is irreversible indicating that the stability of the apoprotein is under kinetic control. This result implies that the stabilization is due to a TMAO-induced reconfiguration of the flexible LPP state, which leads to conformational limitations of the apoprotein likely driven by favorable entropic contribution. Evidence for the conformational perturbation of the apoprotein had been obtained through several biophysical approaches notably analytical ultracentrifugation, circular dichroism, fluorescence spectroscopy, labelling experiments and proteolysis coupled to mass spectrometry. Unexpectedly, TMAO promotes an overall elongation or asymmetrical changes of the hydrodynamic shape of the apoprotein without alteration of the secondary structure. The modulation of the hydrodynamic properties of the protein is associated with diverse inhomogenous conformational changes: loss of the solvent accessible cavities resulting in a dried protein matrix; some side-chain residues initially buried become solvent exposed while some others become hidden. Consequently, the TMAO-induced protein state exhibits impaired capability in the flavin binding process. Our study suggests that the nature of protein conformational changes induced by the chemical chaperones may be specific to protein packing and plasticity. This could be an efficient mechanism by which the cell controls and finely tunes the conformation of the marginally stable LPPs to avoid their inappropriate protein/protein interactions and aggregation. PMID- 27401113 TI - NADPH Oxidase NOX4 Is a Critical Mediator of BRAFV600E-Induced Downregulation of the Sodium/Iodide Symporter in Papillary Thyroid Carcinomas. AB - AIMS: The BRAFV600E oncogene, reported in 40%-60% of papillary thyroid cancer (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS), and therefore with radioiodine refractoriness. Inhibition of mitogen activated protein kinase (MAPK) pathway, constitutively activated by BRAFV600E, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAFV600E adaptive resistance. Recent studies pointed to a key role of transforming growth factor beta (TGF-beta) in BRAFV600E-induced effects. The reactive oxygen species (ROS)-generating NADPH oxidase NOX4, which is increased in PTC, has been identified as a new key effector of TGF-beta in cancer, suggestive of a potential role in BRAFV600E-induced thyroid tumors. RESULTS: Here, using two human BRAFV600E-mutated thyroid cell lines and a rat thyroid cell line expressing BRAFV600E in a conditional manner, we show that NOX4 upregulation is controlled at the transcriptional level by the oncogene via the TGF-beta/Smad3 signaling pathway. Importantly, treatment of cells with NOX4 targeted siRNA downregulates BRAFV600E-induced NIS repression. Innovation and Conclusion: Our results establish a link between BRAFV600E and NOX4, which is confirmed by a comparative analysis of NOX4 expression in human (TCGA) and mouse thyroid cancers. Remarkably, analysis of human and murine BRAFV600E-mutated thyroid tumors highlights that the level of NOX4 expression is inversely correlated to thyroid differentiation suggesting that other genes involved in thyroid differentiation in addition to NIS might be silenced by a mechanism controlled by NOX4-derived ROS. This study opens a new opportunity to optimize thyroid cancer therapy. Antioxid. Redox Signal. 26, 864-877. PMID- 27401115 TI - Assessment of cell line competence for studies of pharmacological GPR30 modulation. AB - CONTEXT/OBJECTIVE: Cell lines used to study the role of the G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor (GPER) as a mediator of estrogen responses have yielded conflicting results. This work identified a simple assay to predict cell line competence for pharmacological studies of GPR30. MATERIALS AND METHODS: The phosphorylation or expression levels of ERK1/2, Akt, c-Fos and eNOS were evaluated to assess GPR30 activation in response to known agonists (17beta-estradiol and G-1) in MCF-7 and T-47D breast cancer cell lines and in bovine aortic endothelial cells. GPR30 expression was analyzed by qRT-PCR and Western blot with two distinct antibodies directed at its carboxy and amino terminals. RESULTS: None of the agonists, at any of the concentrations tested, activated any of those target proteins. Additional experiments excluded the disruption of the signaling pathway, interference of phenol red in the culture medium and constitutive proteasome degradation of GPR30 as possible causes for the lack of response of the three cell lines. Analysis of receptor expression showed the absence of clearly detectable GPR30 species of 44 and 50-55 kDa previously identified in cell lines that respond to 17beta-estradiol and G-1. DISCUSSION AND CONCLUSION: Cells that do not express the 44 and 50-55 kDa species do not respond to GPR30 agonists. Thus, the presence or absence of these GPR30 species is a simple and rapid manner to determine whether a given cell line is suitable for pharmacological or molecular studies of GPR30 modulation. PMID- 27401116 TI - Selective Synthesis of Partially Protected Nonsymmetric Biphenols by Reagent- and Metal-Free Anodic Cross-Coupling Reaction. AB - The oxidative cross-coupling of aromatic substrates without the necessity of leaving groups or catalysts is described. The selective formation of partially protected nonsymmetric 2,2'-biphenols via electroorganic synthesis was accomplished with a high yield of isolated product. Since electric current is employed as the terminal oxidant, the reaction is reagent-free; no reagent waste is generated as only electrons are involved. The reaction is conducted in an undivided cell, and is suitable for scale-up and inherently safe. The implementation of O-silyl-protected phenols in this transformation results in both significantly enhanced yields and higher selectivity for the desired nonsymmetric 2,2'-biphenols. The use of a bulky silyl group to block one hydroxyl moiety makes the final product less prone to oxidation. Furthermore, the partially silyl-protected 2,2'-biphenols are versatile building blocks that usually require tedious or low-yielding synthetic pathways. Additionally, this strategy facilitates a large variety of new substrate combinations for oxidative cross-coupling reactions. PMID- 27401117 TI - The Effects of Ambulatory Accelerations on the Stability of a Magnetically Suspended Impeller for an Implantable Blood Pump. AB - This article describes the effects of ambulatory accelerations on the stability of a magnetically suspended impeller for use in implantable blood pumps. A magnetic suspension system is developed to control the radial position of a magnetic impeller using coils in the pump casing. The magnitude and periodicity of ambulatory accelerations at the torso are measured. A test rig is then designed to apply appropriate accelerations to the suspension system. Accelerations from 0 to 1 g are applied to the suspended impeller with ambulatory periodicity while the radial position of the impeller and power consumption of the suspension system are monitored. The test is carried out with the impeller suspended in air, water, and a glycerol solution to simulate the viscosity of blood. A model is developed to investigate the effects of the radial magnetic suspension system and fluid damping during ambulatory accelerations. The suspension system reduces the average displacement of the impeller suspended in aqueous solutions within its casing to 100 um with a power consumption of below 2 W during higher magnitude ambulatory accelerations (RMS magnitude 0.3 g). The damping effect of the fluid is also examined and it is shown that buoyancy, rather than drag, is the primary cause of the damping at the low displacement oscillations that occur during the application of ambulatory accelerations to such a suspension system. PMID- 27401119 TI - Incidence of serum antibody titers against herpes simplex virus in Japanese patients. AB - Herpes simplex virus (HSV) establishes latency in the sensory neuronal ganglia after primary infection, and occasionally causes recurrent infection, mainly on the lips or genitalia. Previous reports revealed an age-related increase in HSV immunoglobulin G seropositive subjects in a hospital-based study and the general population in Japan. In this report, we retrospectively analyzed the results of serological tests against HSV, in which subjects were diagnosed with or suspected as having HSV infection. A total of 1216 subjects with at least one complement fixation (CF) result were included. Of these, 771 subjects (63.4%) were positive at first visit. When stratified by age, incidence of positive patients linearly increased with age from teenagers (44.9%) to those in their 80s (88.9%). Positivity in women was higher than in men overall; significantly higher incidence was observed in women aged in their 30s, 40s and 60s. When observing changing HSV-CF titers over time in 81 initially negative patients, 18 (22%) seroconverted during the 2121-day observation period. In this study, we clearly show that distribution of HSV-CF titers is similar to previous HSV-immunoglobulin G results. This correlation is probably caused by the continual subclinical proliferation of HSV, thus maintaining CF titers. Our observations provide current data on the incidence of HSV, reconfirming that serological examination is unreliable in diagnosing recurrent herpes, and the majority of infected subjects are asymptomatic. PMID- 27401120 TI - Mechanisms of influenza viral membrane fusion. AB - Influenza viral particles are enveloped by a lipid bilayer. A major step in infection is fusion of the viral and host cellular membranes, a process with large kinetic barriers. Influenza membrane fusion is catalyzed by hemagglutinin (HA), a class I viral fusion protein activated by low pH. The exact nature of the HA conformational changes that deliver the energy required for fusion remains poorly understood. This review summarizes our current knowledge of HA structure and dynamics, describes recent single-particle experiments and modeling studies, and discusses their role in understanding how multiple HAs mediate fusion. These approaches provide a mechanistic picture in which HAs independently and stochastically insert into the target membrane, forming a cluster of HAs that is collectively able to overcome the barrier to membrane fusion. The new experimental and modeling approaches described in this review hold promise for a more complete understanding of other viral fusion systems and the protein systems responsible for cellular fusion. PMID- 27401121 TI - The prognostic value of pretreatment platelet count in patients with head and neck squamous cell carcinoma. AB - OBJECTIVE: Thrombocytosis is commonly observed in patients with solid tumors. This study aimed to evaluate the prognostic role of circulating pretreatment platelet count in a large series of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We retrospectively studied 824 patients with HNSCC treated at a single institution from 2000 to 2012. Disease-specific survival and local, regional, and distant recurrence-free survival were analyzed according to the distribution of the platelet count. RESULTS: By defining the platelet count 250.05*109/L as a cut-off point with the best predictive capacity, we classified the patients into two groups: those with a high platelet count (n=378, 45.9%), and those with a low platelet count (n=446, 54.1%). On univariate analysis, there were significant differences in disease-specific survival depending on pretreatment platelet count (P=0.001). The 5-year specific survival rates were 74.1% (CI 95%: 69.8-78.4%) and 61.6% (CI 95%: 56.4-66.8%) for patients with a low and high platelet count, respectively. According to the results of a multivariate analysis, patients with a high count of platelets had a tendency to a lower disease-specific survival, but the hazard ratio did not reach statistically significant differences (HR 1.24, CI 95%: 0.97-1.61, P=0.085). CONCLUSION: Platelet count was significantly associated with survival in univariate analysis. However, in a multivariate analysis it lost its prognostic capacity, limiting its utility as a prognostic marker in patients with HNSCC. Considering separately each primary tumor location, patients with hypopharyngeal cancer and a high platelet count had a significant decrease of disease-specific survival. PMID- 27401122 TI - The modulatory effect of semantic familiarity on the audiovisual integration of face-name pairs. AB - To recognize individuals, the brain often integrates audiovisual information from familiar or unfamiliar faces, voices, and auditory names. To date, the effects of the semantic familiarity of stimuli on audiovisual integration remain unknown. In this functional magnetic resonance imaging (fMRI) study, we used familiar/unfamiliar facial images, auditory names, and audiovisual face-name pairs as stimuli to determine the influence of semantic familiarity on audiovisual integration. First, we performed a general linear model analysis using fMRI data and found that audiovisual integration occurred for familiar congruent and unfamiliar face-name pairs but not for familiar incongruent pairs. Second, we decoded the familiarity categories of the stimuli (familiar vs. unfamiliar) from the fMRI data and calculated the reproducibility indices of the brain patterns that corresponded to familiar and unfamiliar stimuli. The decoding accuracy rate was significantly higher for familiar congruent versus unfamiliar face-name pairs (83.2%) than for familiar versus unfamiliar faces (63.9%) and for familiar versus unfamiliar names (60.4%). This increase in decoding accuracy was not observed for familiar incongruent versus unfamiliar pairs. Furthermore, compared with the brain patterns associated with facial images or auditory names, the reproducibility index was significantly improved for the brain patterns of familiar congruent face-name pairs but not those of familiar incongruent or unfamiliar pairs. Our results indicate the modulatory effect that semantic familiarity has on audiovisual integration. Specifically, neural representations were enhanced for familiar congruent face-name pairs compared with visual-only faces and auditory-only names, whereas this enhancement effect was not observed for familiar incongruent or unfamiliar pairs. Hum Brain Mapp 37:4333-4348, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27401123 TI - On the Origin of CRISPR-Cas Technology: From Prokaryotes to Mammals. AB - Clustered regularly-interspaced short palindromic repeat (CRISPR) sequences cooperate with CRISPR-associated (Cas) proteins to form the basis of CRISPR-Cas adaptive immune systems in prokaryotes. For more than 20 years, these systems were of interest only to specialists, mainly molecular microbiologists, who tried to understand the properties of this unique defense mechanism. In 2012, the potential of CRISPR-Cas systems was uncovered and these were presented as genome editing tools with an outstanding capacity to trigger targeted genetic modifications that can be applied to virtually any organism. Shortly thereafter, in early 2013, these tools were shown to efficiently drive specific modification of mammalian genomes. This review attempts to summarize, in a comprehensive manner, the key events and milestones that brought CRISPR-Cas technology from prokaryotes to mammals. PMID- 27401124 TI - Spinal cord injury rehabilitation and mental health, SCReaM. AB - AIMS: The aim of the study was to investigate whether people with a pre-existing mental health disorder (MHD) benefit from rehabilitation following a spinal cord injury (SCI) and how their outcomes differ from those without a pre-existing MHD. METHODS: Rehabilitation outcomes of a cohort of patients with pre-existing MHD discharged from the London SCI Centre over a 6-year period were investigated. A retrospective matched case-control study design was used to compare the Spinal Cord Independence Measure III between those with an SCI and pre-existing MHD and those without and both compared with published expected outcomes. RESULTS: The study found that, overall, those with MHD do benefit from SCI rehabilitation and that their outcomes do not significantly differ from those without MHD. Furthermore, the outcomes were favourable when compared with published expected outcomes. CONCLUSION: Having a pre-existing MHD does not preclude patients with an SCI from benefiting from rehabilitation. These findings are an important basis on which to ensure equal access to rehabilitation for patients with a pre existing MHD. PMID- 27401125 TI - The reliability of measuring wound undermining in people with spinal cord injury. AB - OBJECTIVE: The objective of this study was to determine the reliability of measuring wound undermining in people with spinal cord injury (SCI). STUDY DESIGN: A psychometric study. SETTING: The study was conducted at the Indian Spinal Injuries Centre, New Delhi, India. PARTICIPANTS: Thirty people with a complete or incomplete SCI and a pressure ulcer with wound undermining were recruited. METHODS: Wound undermining was measured using the four cardinal points from a clock face (with 12 O'clock defined as towards the head). Inter-rater reliability was tested by comparing the wound undermining scores from two different assessors. Intra-rater reliability was tested by comparing the wound undermining scores from the same assessor on two different days. RESULTS: The intraclass correlation coefficients (95% confidence interval) for inter-rater and intra-rater reliability were 0.996 (0.992-0.999) and 0.998 (0.996-0.999), respectively. Repeat measurements by the same and different assessor were within 0.3 cm of each other, 80% and 83% of the time, respectively. CONCLUSION: Measurements of wound undermining have excellent reliability. PMID- 27401126 TI - Spinal cord injury and women's sexual life: case-control study. AB - : Study design :This is a case-control study. OBJECTIVE: The objective of this study was to estimate the magnitude of association between spinal cord injury (SCI) and women's quality of sexual life and sexual function. SETTING: This study was conducted in the Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. METHODS: From the referral university-based clinics, we used simple random sampling to recruit 62 women: 31 women with SCI and 31 women without SCI. Socio-demographic and reproductive traits questionnaire, Sexual Quality of life-Female (SQOL-F), Female Sexual Function Index (FSFI) and Spinal Cord Independence Measure (SCIM) were completed using telephone and face-to-face interviews in the cases and controls. After univariate analyses, multivariate linear and proportional odds regression models were conducted to investigate the relation between SCI and women's quality of sexual life, as well as sexual function. RESULTS: The mean age of cases and controls was 35.42+/-6.51 and 33.77+/-4.02 years. Most women were high school educated and housewives. Adjusting for probable confounders, the proportional odds regression model showed a significant relationship between the spinal cord injury (AOR=4.2, 95% CI: 1.8-9.2), non-college-educated (AOR=3.1, 95% CI: 1.2 5.9) and employed (AOR=1.8, 95% CI: 1.1-1.8) variables and being in one of the moderate or poor quality of life classes. Scores of SQOL-F and FSFI domains, except satisfaction, were significantly worse in cases versus controls (P<0.001). CONCLUSION: Although our participants showed low sexual dysfunction, they tended to report moderate to poor quality of sexual life. Our findings support the implication that sexual rehabilitation must be provided for women with SCI soon after injury. PMID- 27401127 TI - Physiological responses between players with and without spinal cord injury in wheelchair basketball small-sided games. AB - STUDY DESIGN: This is a comparative study between players with and without spinal cord injury (SCI) during a training task. OBJECTIVE: This study examined physiological responses in commonly used small-sided games (SSGs) in well experienced wheelchair basketball (WB) players with SCI and without SCI (Non SCI). SETTING: The study was conducted with a WB team in Vitoria-Gasteiz, Spain (2014). METHODS: The team was divided into an SCI group (n=6) and a Non-SCI group (n=6). Absolute and relative heart rate (HR) along with tympanic temperature and perceived exertion (RPE) were recorded for both groups. RESULTS: The two groups attained different absolute HR values for the same SSG. However, no significant differences were observed in relative HR between groups (%HRmean, %HRpeak and the percentage of the time spent in each HR zone: low, moderate, high and maximal) nor in tympanic temperature. Moreover, in relation to the bout evolution analysis (4 repetitions of 4 min), the Non-SCI group significantly increased (P<0.05) absolute HRmean and HRpeak during bouts, whereas the SCI group maintained them constant. Furthermore, the variations in the percentage of the time spent in each HR zone only were observed in the Non-SCI group. CONCLUSION: In spite of the Non SCI group attaining higher absolute HR values, the SCI and Non-SCI groups may have similar HR relative values during a specific WB training task. However, the SCI group reported significantly higher values in respiratory RPE in the last bout than the Non-SCI group for the same SSG. PMID- 27401128 TI - Version 2.0 of the international spinal cord injury endocrinology and metabolic function basic data set. PMID- 27401129 TI - Phenotypic and functional characterization of in vitro cultured human mast cells. AB - BACKGROUND: Mast cell progenitor cells, derived from CD34+ hematopoietic stem cells, enter the circulation and subsequently mucosal or connective tissues where they mature to mast cells. Upon activation, mast cells increase the expression of activation markers, e.g. CD63, and release histamine amongst other mediators. Traditionally, release of these mediators is quantified using assays measuring their extracellular concentration in the supernatant of stimulated cells. METHODS: Human mast cells (HuMC) were cultured from peripheral blood, phenotypically characterized, passively sensitized with allogenic IgE antibodies and finally stimulated by anti-IgE that crosslinks IgE/FcepsilonRI complexes. Alterations in the number of cells positive for CD63 and release of histamine were quantified simultaneously by flow cytometry. RESULTS: In culture, two distinct CD45+ cell populations were identified: CD117+ CD203c+hi and CD117- CD203c+low cells. Both populations showed positivity for FcepsilonRI, tryptase and chymase, and contained histamine. Activation resulted in a significant increase of cells positive for CD63+ up to 21% (range: 11-39) for CD117+ CD203c+hi cells (P = 0.005), and 27% (18-55) CD63+ for CD117- CD203c+low cells (P = 0.02). Baseline histamine content was higher for CD117+ CD203c+hi cells than for CD117- CD203c+low cells, respectively 994 (695-6815) Molecules of Equivalent Specific Fluorochrome V500 per cell (MESF-V500/cell) and 797 (629-4978) MESF V500/cell (P = 0.02). After activation, CD117+ CD203c+hi cells showed significant histamine release of 578 (366-1521) MESF-V500/cell, whilst CD117- CD203c+low cells resulted in 310 (217-366) MESF-V500/cell histamine release. CONCLUSION: This study discloses that culturing HuMC from CD34+ progenitors yields 2 phenotypically distinct cell populations that display a greatly similar response upon cross-linking of IgE/FcepsilonRI complexes. (c) 2016 International Clinical Cytometry Society. PMID- 27401130 TI - Preparation of polymer-blended quinine nanocomposite particles by spray drying and assessment of their instrumental bitterness-masking effect using a taste sensor. AB - CONTEXT: The development of taste-masking technologies for foods and drugs is essential because it would enable people to consume and receive healthy and therapeutic effect without distress. OBJECTIVE: In the current study, in order to develop a novel method to prepare nanocomposite particles (microparticles containing bitter nanoparticles) in only one step, by using spray drying, a two solution mixing nozzle-equipped spray dryer that we previously reported was used. The nanocomposite particles with or without poorly water-soluble polymers prepared using our spray-drying technique were characterized. METHODS: (1) The organic solution containing quinine, a model of bitter compound and poorly water soluble polymers and (2) sugar alcohol (mannitol) aqueous solution were separately flown in tubes and two solutions were spray dried through two-solution type spray nozzle to prepare polymer-blended quinine nanocomposite particles. Mean diameters of nanoparticles, taste-masking effect and dissolution rate of quinine were evaluated. RESULTS: The results of taste masking by taste sensor suggested that the polymer (Eudragit EPO, Eudragit S100 or Ethyl cellulose) blended quinine nanocomposite particles exhibited marked masking of instrumental quinine bitterness compared with the quinine nanocomposite particles alone. Quinine nanocomposite formulations altered the quinine dissolution rate, indicating that they can control intestinal absorption of quinine. CONCLUSION: These results suggest that polymer-blended quinine composite particles prepared using our spray-drying technique are useful for masking bitter tastes in the field of food and pharmaceutical industry. PMID- 27401131 TI - A Kinect(TM) camera based navigation system for percutaneous abdominal puncture. AB - Percutaneous abdominal puncture is a popular interventional method for the management of abdominal tumors. Image-guided puncture can help interventional radiologists improve targeting accuracy. The second generation of Kinect(TM) was released recently, we developed an optical navigation system to investigate its feasibility for guiding percutaneous abdominal puncture, and compare its performance on needle insertion guidance with that of the first-generation Kinect(TM). For physical-to-image registration in this system, two surfaces extracted from preoperative CT and intraoperative Kinect(TM) depth images were matched using an iterative closest point (ICP) algorithm. A 2D shape image-based correspondence searching algorithm was proposed for generating a close initial position before ICP matching. Evaluation experiments were conducted on an abdominal phantom and six beagles in vivo. For phantom study, a two-factor experiment was designed to evaluate the effect of the operator's skill and trajectory on target positioning error (TPE). A total of 36 needle punctures were tested on a Kinect(TM) for Windows version 2 (Kinect(TM) V2). The target registration error (TRE), user error, and TPE are 4.26 +/- 1.94 mm, 2.92 +/- 1.67 mm, and 5.23 +/- 2.29 mm, respectively. No statistically significant differences in TPE regarding operator's skill and trajectory are observed. Additionally, a Kinect(TM) for Windows version 1 (Kinect(TM) V1) was tested with 12 insertions, and the TRE evaluated with the Kinect(TM) V1 is statistically significantly larger than that with the Kinect(TM) V2. For the animal experiment, fifteen artificial liver tumors were inserted guided by the navigation system. The TPE was evaluated as 6.40 +/- 2.72 mm, and its lateral and longitudinal component were 4.30 +/- 2.51 mm and 3.80 +/- 3.11 mm, respectively. This study demonstrates that the navigation accuracy of the proposed system is acceptable, and that the second generation Kinect(TM)-based navigation is superior to the first-generation Kinect(TM), and has potential of clinical application in percutaneous abdominal puncture. PMID- 27401132 TI - vcfr: a package to manipulate and visualize variant call format data in R. AB - Software to call single-nucleotide polymorphisms or related genetic variants has converged on the variant call format (VCF) as the output format of choice. This has created a need for tools to work with VCF files. While an increasing number of software exists to read VCF data, many only extract the genotypes without including the data associated with each genotype that describes its quality. We created the r package vcfr to address this issue. We developed a VCF file exploration tool implemented in the r language because r provides an interactive experience and an environment that is commonly used for genetic data analysis. Functions to read and write VCF files into r as well as functions to extract portions of the data and to plot summary statistics of the data are implemented. vcfr further provides the ability to visualize how various parameterizations of the data affect the results. Additional tools are included to integrate sequence (fasta) and annotation data (GFF) for visualization of genomic regions such as chromosomes. Conversion functions translate data from the vcfr data structure to formats used by other r genetics packages. Computationally intensive functions are implemented in C++ to improve performance. Use of these tools is intended to facilitate VCF data exploration, including intuitive methods for data quality control and easy export to other r packages for further analysis. vcfr thus provides essential, novel tools currently not available in r. PMID- 27401133 TI - Inhibiting cortical protein kinase A in spinal cord injured rats enhances efficacy of rehabilitative training. AB - Elevated levels of the second messenger molecule cyclic adenosine monophosphate (cAMP) are often associated with neuron sprouting and neurite extension (i.e., neuroplasticity). Phosphokinase A (PKA) is a prominent downstream target of cAMP that has been associated with neurite outgrowth. We hypothesized that rehabilitative motor training following spinal cord injuries promotes neuroplasticity via PKA activation. However, in two independent experiments, inhibition of cortical PKA using Rp-cAMPS throughout rehabilitative training robustly increased functional recovery and collateral sprouting of injured corticospinal tract axons, an indicator of neuroplasticity. Consistent with these in vivo findings, using cultured STHdh neurons, we found that Rp-cAMPS had no effect on the phosphorylation of CREB (cAMP response element-binding protein), a prominent downstream target of PKA, even with the concomitant application of the adenylate cyclase agonist forskolin to increase cAMP levels. Conversely, when cAMP levels were increased using the phosphodiesterase inhibitor IBMX, Rp-cAMPS potently inhibited CREB phosphorylation. Taken together, our results suggest that an alternate cAMP dependent pathway was involved in increasing CREB phosphorylation and neuroplasticity. This idea was supported by an in vitro neurite outgrowth assay, where inhibiting PKA did enhance neurite outgrowth. However, when PKA inhibition was combined with inhibition of EPAC2 (exchange protein directly activated by cAMP), another downstream target of cAMP in neurons, neurite outgrowth was significantly reduced. In conclusion, blocking PKA in cortical neurons of spinal cord injured rats increases neurite outgrowth of the lesioned corticospinal tract fibres and the efficacy of rehabilitative training, likely via EPAC. PMID- 27401134 TI - Influence of parity and sexual history on cytomegalovirus seroprevalence among women aged 20-49 years in the USA. AB - OBJECTIVE: To assess the influence of parity, as a proxy for exposure to children, and sexual history on cytomegalovirus (CMV) seroprevalence. METHODS: Data were retrospectively analyzed from women aged 20-49 years who were tested for CMV immunoglobulin G antibodies in the 1999-2004 National Health and Nutrition Examination Survey, a nationally representative survey of the US population. Logistic regression was used to determine independent variables associated with CMV seroprevalence. RESULTS: Among 3710 women, the age-adjusted CMV seroprevalence was 61.3% (95% CI 58.9%-63.6%). In age-adjusted univariate analysis, women who had given birth at least once had higher overall CMV seroprevalence (66.0%, 95% CI 63.1%-68.9%) than did those who had not given birth (49.0%, 95% CI 44.4%-53.7%; P<0.001). In multivariate logistic analysis, higher CMV seroprevalence was independently associated with number of live births (each additional birth: adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.3), age at first sexual intercourse (<18 vs >=18years: aOR 1.3, 95% CI 1.1-1.6), lifetime sexual partners (>=10 vs <10: aOR 1.4, 95% CI 1.1-1.9), and herpes type 2 seropositivity (aOR 1.9, 95% CI 1.5-2.6) after controlling for age, race/Hispanic origin, place of birth, poverty index, and education. CONCLUSION: Among US women of reproductive age, parity and sexual exposures were independently associated with increased CMV seroprevalence. PMID- 27401135 TI - Surface-Enhanced Raman Spectroscopy on Liquid Interfacial Nanoparticle Arrays for Multiplex Detecting Drugs in Urine. AB - The design and application of liquid interfacial plasmonic platform is still in its infancy but is an exciting topic in tunable optical devices, sensors, and catalysis. Here, we developed an interfacial surface-enhanced Raman scattering (SERS) platform through the large-scale self-assembly of gold nanoparticle (GNP) arrays at the cyclohexane (CYH)/water interface for detecting trace drug molecules in the urine of humans. The molecules extracted by the CYH phase from a urine sample were directly localized into the self-organized plasmonic hotspots, yielded excellent Raman enhancement, and realized the substrate-free interfacial SERS detection. Synchrotron radiation small-angle X-ray scattering (SR-SAXS) experiments reveals a good uniformity of approximately 2-3 nm interparticle distance in the GNP arrays. SERS colocalization experiments demonstrated that amphetamine molecules of different concentration levels could be loaded into the interfacial GNP arrays and realized the coassembly together with nanoparticles at the liquid/liquid interface. Interfacial GNP arrays with dynamic nanogaps in liquid interfacial structure can make surrounding molecules easily diffuse into the nanogaps. In contrast, the fixed GNP arrays on Si wafer were more irregular, such as multilayer stack, random aggregates, and voids, during the drying process. When the drugs directly participate in the self-assembly process, it becomes easier for analytes diffusing into the nanogaps of GNP arrays, produces a concentration effect, and amplified the SERS sensitivity. This feature also enables molecules to be adsorbed evenly in the arrays and makes a more uniform distribution of both the analytes and GNPs in the liquid interface and realizes the significant increase in signal reproducibility. Interfacial SERS produced a standard deviation of 12.5% at 1001 cm(-1) peak of methamphetamine (MAMP) molecules under the concentration of 1 ppm, implying a good reproducibility. Moreover, dual-analyte detection at organic and aqueous phases was also realized and confirmed a good capability for analytes detection by liquid interfacial SERS platform, which promises nonengineering detection of analytes dissolved in often inaccessible environments. PMID- 27401136 TI - Experimental models for dynamic compartmentalization of biomolecules in liquid organelles: Reversible formation and partitioning in aqueous biphasic systems. AB - Living cells contain numerous subcellular compartments, many of which lack membranous boundaries and are thought to occur due to liquid-liquid phase coexistence. This review will introduce these biological membraneless organelles and discuss simple experimental models based on liquid-liquid phase separation in polymer solutions. When more than one phase is present, solutes such as proteins or nucleic acids can be compartmentalized by partitioning into one of the phases. This could confer benefits to the cell such as enhanced reaction rates or sequestration of toxic molecules. Liquid-like compartments inside living cells are often dynamic, for example, appearing and disappearing in response to stimuli and/or at different points in the cell cycle. We will discuss mechanisms by which phase transitions can be induced in the laboratory and inside living cells, with special emphasis on regulating phase formation by phosphorylation state. This work is motivated by a desire to understand the physical and chemical mechanisms that underlie biological processes and to enable new nonbiological applications. PMID- 27401137 TI - Next-generation sequencing for molecular diagnosis of autosomal recessive polycystic kidney disease. AB - Autosomal recessive polycystic kidney disease (ARPKD) a rare genetic disorder, described by formation of cysts in the kidney. A targeted customized sequencing of genes implicated in ARPKD phenotype was performed to identify candidate variants using the Ion torrent PGM next-generation sequencing. The results identified likely pathogenic disease causing variants during the validation process. Four potential pathogenic variants [c.4870C>T, p.(Arg1624Trp)], [c.5725C>T, p.(Arg1909Trp)], c.1736C>T, p.(Thr579Met)] and [(c.10628T>G), p.(Leu3543Trp)] were observed in PKHD1 gene among 12 out of 18 samples. The rest of the patient samples also showed few variants in ADPKD (Autosomal Dominant Polycystic Kidney Disease) disease causing genes PKD1 and PKD2 i.e. [c.12433G>A, p.(Val4145Ile)] and [c.1445T>G, p.(Phe482Cys)], respectively. All causative variants were validated by capillary sequencing, confirming the presence of a novel homozygous variants [c.10628T>G, p.(Leu3543Trp)] found in exon 61 of a male proband. All potentially deleterious variants identified in PKHD1, PKD1, and PKD2 gene, also exhibited pathologically or clinically significance based on the computational predictions involved in predicting the impact of non-synonymous SNPs (nsSNPs) on protein function such as Sorting Intolerant From Tolerant (SIFT) and Polymorphism Phenotyping (PolyPhen2). SIFT classified 50% of our nsSNPs as "deleterious", while PolyPhen2 identified 45% of our nsSNPs as "Probably damaged" and the results from both programs were largely complementary. Taken together, these results suggest that the NGS strategies provide a fast, accurate and cost effective molecular diagnostic tool for identifying mutations in targeted genes sequence analysis. PMID- 27401138 TI - A R/K-rich motif in the C-terminal of the homeodomain is required for complete translocating of NKX2.5 protein into nucleus. AB - NKX2.5 plays important roles in heart development. Being a transcription factor, NKX2.5 exerts its biological functions in nucleus. However, the sequence motif that localize NKX2.5 into nucleus is still not clear. Here, we found a R/K-rich sequence motif from Q187 to R197 (QNRRYKCKRQR) was required for exclusive nuclear localization of NKX2.5. Eight truncated plasmids (E109X, Q149X, Q170X, Q187X, Q198X, Y256X, Y259X, and C264X) which were associated with congenital heart disease (CHD) were constructed. Compared with the wild type NKX2.5, the proteins E109X, Q149X, Q170X, Q187X without intact homeodomain (HD) showed no transcriptional activity while Q198X, Y256X, Y259X and C264X with intact HD showed 50 to 66% transcriptional activity. E109X, Q149X, Q170X, Q187X without intact HD localized in the cytoplasm and nucleus simultaneously and Q198X, Y256X, Y259X and C264X with intact HD localized completely in nucleus. These results inferred the indispensability of 187QNRRYKCKRQR197 in exclusive nucleus localization. Additionally, this sequence motif was very conservative among human, mouse and rat, indicating this motif was important for NKX2.5 function. Thus, we concluded that R/K-rich sequence motif 187QNRRYKCKRQR197 played a central role for NKX2.5 nuclear localization. Our findings provided a clue to understand the mechanisms between the truncated NKX2.5 mutants and CHD. PMID- 27401139 TI - Fatigue: a distressing symptom for patients with irritable bowel syndrome. AB - BACKGROUND: Fatigue is a frequent symptom in patients with irritable bowel syndrome (IBS), and is associated with poor quality of life. However, few studies have evaluated its impact on daily life or the perceived distress it can cause. Using a multi-methods approach, this study describes the impact and manifestations of fatigue in patients with IBS and investigates the relationship between fatigue severity and illness-related and health-promoting factors. METHODS: A total of 160 patients with IBS completed self-reported questionnaires assessing fatigue, gastrointestinal symptoms, psychological distress, and sense of coherence. Fatigue was assessed with the Fatigue Impact Scale, which also includes structured and open-ended questions which were analyzed with a deductive qualitative analysis. Patients were classified as having severe, moderate, or mild fatigue based on frequency, distress and impact on daily life. KEY RESULTS: The open-ended questions revealed a multidimensional impact on life. Fatigue mainly interfered with the ability to perform physical activities, work, and domestic work, and the ability to interact socially. Decreased stamina was evident, along with strategies to limit the bodily consequences of tiredness. Severe fatigue was accompanied by more severe IBS symptoms, anxiety and depression and lower sense of coherence. CONCLUSIONS & INFERENCES: Fatigue is a distressing symptom which occurs in a sizeable proportion of patients with IBS. It affects life in a multidimensional way, with poor bodily stamina being the most prominent feature. Fatigue, along with sense of coherence, depression and anxiety, needs to be assessed, confirmed and targeted for interventions. PMID- 27401140 TI - Adenosine Selectively Depletes Alloreactive T Cells to Prevent GVHD While Conserving Immunity to Viruses and Leukemia. AB - Selective depletion (SD) of alloreactive T cells from allogeneic hematopoeitic stem cell transplants to prevent graft-versus-host disease (GVHD) without compromising immune reconstitution and antitumor responses remains a challenge. Here, we demonstrate a novel SD strategy whereby alloreacting T cells are efficiently deleted ex vivo with adenosine. SD was achieved in human leukocyte antigen (HLA) mismatched cocultures by multiple exposures to 2 mmol/l adenosine over 7 days. Adenosine depleted greater than to 90% of alloproliferating T cells in mismatched, haploidentical, and matched sibling pairs while conserving response to third-party antigens. Alloreactive CD4 and CD8 T cells were targeted for depletion while NK and B cells were preserved. Our novel approach also preserved nonalloreactive naive, central, and effector memory T-cell subsets, Tregs, and notably preserved T-cell responses against DNA viruses that contribute to transplant related mortality after allogeneic hematopoeitic stem cell transplants. Additionally, T cells recognizing leukemia-associated antigens were efficiently generated in vitro from the cell product post-SD. This study is the first to demonstrate that adenosine depletion of alloactivated T cells maintains a complete immune cell profile and recall viral responses. Expansion of tumor antigen-specific subsets postdepletion opens the possibility of generating T-cell products capable of graft-versus-tumor responses without causing GVHD. PMID- 27401143 TI - Use of post-thaw semen quality parameters to predict fertility of water buffalo (Bubalus bubalis) bull during peak breeding season. AB - This study was designed to predict the fertility of water buffalo bull using post thaw semen quality parameters during peak breeding season. Thirty ejaculates were collected from five bulls with artificial vagina and cryopreserved. At post-thaw, semen was analysed for motility parameters, velocity distribution, kinematics, DNA integrity/fragmentation, viability, mitochondrial transmembrane potential, morphology, plasma membrane and acrosome integrity. Data of 514 inseminations were collected for estimation of in vivo fertility. Pearson's correlation coefficients showed that progressive motility (PM), rapid velocity, average path velocity, straight line velocity, straightness, supravital plasma membrane integrity, viable spermatozoon with intact acrosome or with high mitochondrial activity were correlated with in vivo fertility (r = .81, p < .01; r = .85, p < .01; r = .64, p < .05; r = .73, p < .05; r = .57, p < .05; r = .88, p < .01; r = .84, p < .01 and r = .81, p < .01 respectively). Step forward multiple regression analysis showed that the best single predictor of fertility was PM. However, combinations of semen quality parameters to predict fertility were better as compared to single parameter. In conclusion, fertility of buffalo bull can be predicted through some of the post-thaw in vitro semen quality tests during peak breeding season. PMID- 27401141 TI - Feasibility and Safety of RNA-transfected CD20-specific Chimeric Antigen Receptor T Cells in Dogs with Spontaneous B Cell Lymphoma. AB - Preclinical murine models of chimeric antigen receptor (CAR) T cell therapy are widely applied, but are greatly limited by their inability to model the complex human tumor microenvironment and adequately predict safety and efficacy in patients. We therefore sought to develop a system that would enable us to evaluate CAR T cell therapies in dogs with spontaneous cancers. We developed an expansion methodology that yields large numbers of canine T cells from normal or lymphoma-diseased dogs. mRNA electroporation was utilized to express a first generation canine CD20-specific CAR in expanded T cells. The canine CD20 (cCD20) CAR expression was efficient and transient, and electroporated T cells exhibited antigen-specific interferon-gamma (IFN-gamma) secretion and lysed cCD20+ targets. In a first-in-canine study, autologous cCD20-zeta CAR T cells were administered to a dog with relapsed B cell lymphoma. Treatment was well tolerated and led to a modest, but transient, antitumor activity, suggesting that stable CAR expression will be necessary for durable clinical remissions. Our study establishes the methodologies necessary to evaluate CAR T cell therapy in dogs with spontaneous malignancies and lays the foundation for use of outbred canine cancer patients to evaluate the safety and efficacy of next-generation CAR therapies and their optimization prior to translation into humans. PMID- 27401142 TI - Optimization of Morpholino Antisense Oligonucleotides Targeting the Intronic Repressor Element1 in Spinal Muscular Atrophy. AB - Loss of Survival Motor Neuron-1 (SMN1) causes Spinal Muscular Atrophy, a devastating neurodegenerative disease. SMN2 is a nearly identical copy gene; however SMN2 cannot prevent disease development in the absence of SMN1 since the majority of SMN2-derived transcripts are alternatively spliced, encoding a truncated, unstable protein lacking exon 7. Nevertheless, SMN2 retains the ability to produce low levels of functional protein. Previously we have described a splice-switching Morpholino antisense oligonucleotide (ASO) sequence that targets a potent intronic repressor, Element1 (E1), located upstream of SMN2 exon 7. In this study, we have assessed a novel panel of Morpholino ASOs with the goal of optimizing E1 ASO activity. Screening for efficacy in the SMNDelta7 mouse model, a single ASO variant was more active in vivo compared with the original E1(MO)-ASO. Sequence variant eleven (E1(MOv11)) consistently showed greater efficacy by increasing the lifespan of severe Spinal Muscular Atrophy mice after a single intracerebroventricular injection in the central nervous system, exhibited a strong dose-response across an order of magnitude, and demonstrated excellent target engagement by partially reversing the pathogenic SMN2 splicing event. We conclude that Morpholino modified ASOs are effective in modifying SMN2 splicing and have the potential for future Spinal Muscular Atrophy clinical applications. PMID- 27401144 TI - Egg and fourth instar larvae gut of Aedes aegypti as a source of stem cells. AB - According to the World Health Organization, 2015 registered more than 1.206.172 cases of Dengue in the Americas. Recently, the Aedes aegypti has been not only related to Dengue, but also with cases of Zika virus and Chikungunya. Due to its epidemiological importance, this study characterized the morphology of the embryonated eggs of A. aegypti and provided a protocol to culture stem cells from eggs and digestive tract of fourth instar larvae in order to examine cell biology and expression of markers in these vectors. Cells were isolated and cultured in DMEM-High at 28 degrees C, and their morphology, cell cycle and immunophenotyping were examined. Morphologically, embryos were at the end of the embryonic period and showed: head, thorax, and abdomen with eight abdominal segments. The embryonic tissues expressed markers related to cell proliferation (PCNA), pluripotency (Sox2 and OCT3/4), neural cells (Nestin), mesenchymal cells (Vimentin and Stro-1), and endosomal cells (GM130 and RAB5). In culture, cells from both tissues (eggs and larvae gut) were composed by a heterogeneous population. The cells had a globoid shape and small size. Cell cycle analysis on passage 1 (P1) showed 27.5%+/-2.0% of cell debris, 68% of cells on G0-G1 phase, 30.2% on S phase, 1.9%+/-0.5% on G2-M phase. In addition, cells on passage 2 showed: 10% of cell debris, 92.4% of cells on G0-G1 phase, 6.8% on S phase, 0.6% on G2-M phase. Embryonated eggs expressed markers involved with pluripotency (Sox2 and Oct 3/4), mesenchymal cells (vimentin and Stro-1), neural cells (Nestin), and cellular death by apoptosis (Caspase 3). Specific endosomal markers for insect cells (GM130 and RAB5) were also highly expressed. In cell culture of A. aegypti larvae gut the same labeling pattern was observed, with a small decrease in the expression of mesenchymal (vimentin and Stro-1) and neural (Nestin) markers. In summary, we were able to establish a protocol to culture embryonated eggs and larvae gut of A. aegypti, describing the characteristics of undifferentiated cells, as well as the cell cycle and expression of markers, which can be used for biotechnology studies for the biological control of this vector. PMID- 27401145 TI - TMEM165 deficiencies in Congenital Disorders of Glycosylation type II (CDG-II): Clues and evidences for roles of the protein in Golgi functions and ion homeostasis. AB - Congenital Disorders of Glycosylation (CDG) are rare inherited diseases causing glycosylation defects responsible for severe growth and psychomotor retardations in patients. Whereas most genetic defects affect enzymes directly involved in the glycosylation process, like glycosyltransferases or sugar transporters, recent findings revealed the impact of gene mutations on proteins implicated in both Golgi vesicular trafficking and ion homeostasis. TMEM165 is one of these deficient Golgi proteins found in CDG patients whose function in the secretory pathway has been deduced from several recent studies using TMEM165 deficient mammalian cells or yeast cells deficient in Gtd1p, the yeast TMEM165 ortholog. These studies actually confirm previous observations based on both sequence and predicted topology of this transmembrane protein and the phenotypes of human and yeast cells, namely that TMEM165 is very probably a transporter involved in ion homeostasis. Whereas the exact function of TMEM165 remains to be fully characterized, several studies hypothesize that TMEM165 could be a Golgi localized Ca2+/H+ antiporter. However, recent data also support the role of TMEM165 in Golgi Mn2+ homeostasis then arguing for a putative role of Mn2+ transporter for TMEM165 essential to achieve the correct N-glycosylation process of proteins in the secretory pathway. This manuscript is a review of the current state of knowledge on TMEM165 deficiencies in Congenital Disorders of Glycosylation as well as new data on function of TMEM165 and some speculative models on TMEM165/Golgi functions are discussed. PMID- 27401146 TI - Examining the role of positive and negative metacognitive beliefs in depression. AB - Many psychological models have been developed to explain the development and maintenance of depression. The most widely evaluated model is the cognitive model of depression, and it is against this model that emerging models should be compared. Accordingly, this cross-sectional study examined whether metacognitive beliefs, as specified in the metacognitive model of depression, would explain additional variance in depressive symptoms over dysfunctional attitudes; the core feature of the cognitive model. Moreover, mediational relationships between metacognitive beliefs, rumination, and depressive symptoms, predicted by the metacognitive model were also explored, whilst controlling for dysfunctional attitudes. A sample of 715 students completed self-report questionnaires measuring depressive symptoms, rumination, dysfunctional attitudes, and metacognitive beliefs. Regression analyses showed that metacognitive beliefs made a significant statistical contribution to depressive symptoms, after controlling for age, gender, rumination and dysfunctional attitudes. Furthermore, as predicted by the metacognitive model, the relationship between positive metacognitive beliefs and depressive symptoms was fully mediated by rumination, whilst the relationship between negative metacognitive beliefs about uncontrollability and danger and depressive symptoms was partially mediated by rumination. The results provide further empirical support for the metacognitive model of depression and indicate that positive and negative metacognitive beliefs play an integral role in the maintenance of depressive symptoms. PMID- 27401147 TI - The European Union Joint Procurement Agreement for cross-border health threats: what is the potential for this new mechanism of health system collaboration? AB - The Joint Procurement Agreement (JPA) is an innovative instrument for multi country procurement of medical countermeasures against cross-border health threats. This paper aims to assess its potential performance. A literature review was conducted to identify key features of successful joint procurement programmes. Documentary analysis and a key informants' interview were carried out to analyse the European Union (EU) JPA. Ownership, equity, transparency, stable central financing, standardisation, flexibility and gradual development were identified as important prerequisites for successful establishment of multi country joint procurement programmes in the literature while security of supply, favourable prices, reduction of operational costs and administrative burden and creation of professional expert networks were identified as desirable outcomes. The EU JPA appears to fulfil the criteria of ownership, transparency, equity, flexibility and gradual development. Standardisation is only partly fulfilled and central EU level financing is not provided. Security of supply is an important outcome for all EU Member States (MS). Price savings, reduction in administrative burden and creation of professional networks may be particularly attractive for the smaller MS. The JPA has the potential to increase health system collaboration and efficiency at EU level provided that the incentives for sustained commitment of larger MS are sufficiently attractive. PMID- 27401149 TI - Novel fusion genes and chimeric transcripts in ependymal tumors. AB - We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. (c) 2016 Wiley Periodicals, Inc. PMID- 27401148 TI - Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice. AB - BACKGROUND: Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. METHODS: The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. RESULTS: pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-alpha and IL-1beta upregulation induced by pIONL. TNF alpha inhibitor (Etanercept) and IL-1beta inhibitor (Diacerein) attenuated pIONL induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-alpha and IL 1beta in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-alpha and IL-1beta upregulation. CONCLUSIONS: CXCL13 and CXCR5 contribute to orofacial pain via ERK mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF alpha and IL-1beta pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain. PMID- 27401150 TI - Deferring allogeneic transplantation for adult acute lymphoblastic leukemia: is there a second chance? PMID- 27401151 TI - Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge. AB - Novel systemic therapies with anti-tumor activity in the brain including small molecules targeting BRAF and MEK, and immune checkpoint inhibition, offer the possibility of improved control of intracranial disease. A number of prospective trials support the judicious use of modern systemic therapies in patients with melanoma and limited brain metastases .The intracranial clinical course of patients who progress extracranially on BRAF/MEK inhibition remains poorly described in the literature. In this report, we highlight a series of clinical cases, with rapid progression of intracranial disease following discontinuation of dabrafenib/trametinib for extracranial disease progression or toxicity, a previously unreported finding in the medical literature with significant implications for patient care. PMID- 27401152 TI - Clinical ramifications of "genomic staging" of low-grade gliomas. AB - "Low-grade gliomas" (LGGs), classification of which is derived from histopathological observations, exhibit significant heterogeneity in clinical behavior. Recently, increasing attention has been paid to genomic analyses of these tumors, to aid in treatment and prognostic decision-making. We discuss herein the recent genomic analysis of gliomas from two major recent publications, and also the results of seminal LGG trials in the context of molecular and genomic stratification, with respect to both prognosis and response to therapy. We also analyze implications of these "molecular classifications". We propose separating out the worst prognostic subsets, whose outcomes resemble those of glioblastoma patients. Lastly, a brief discussion is provided regarding translating this collective knowledge into the clinic and in treatment decisions; also addressed are some of the many questions that still need to be examined in light of these strong and emerging data. PMID- 27401153 TI - SHP-1 promoter 2 methylation in cerebrospinal fluid for diagnosis of leptomeningeal epithelial-derived malignancy (carcinomatous meningitis). AB - Current diagnostic methods for leptomeningeal metastasis (LM) from epithelial derived malignancy (EDM) have limited sensitivity. Here, we explored SHP-1 promoter 2 methylation (SHP1P2)-an epithelial-specific methylation marker previously proven as risk stratification and potential diagnostic marker in non small cell lung cancer-for EDM with LM. We prospectively recruited 136 patients who were diagnosed EDM with LM (n = 25), EDM without LM (n = 14), non-EDM with LM (n = 8), and benign meningeal diseases (n = 89). The primary cancer sites for EDM with LM were lung (n = 17), breast (n = 5), and colon (n = 3). We performed quantitative analyses of cell-free (cfSHP1P2) and whole fraction (wSHP1P2) from cerebrospinal fluid (CSF); results were correlated with the clinicopathological data, including CSF cytology. Median cfSHP1P2 and wSHP1P2 were 3.08 [range: 0 163.5] and 9.35 [0.69-91.63] ng/ml, respectively, in EDM with LM; 0 [0-0.08] and 0.23 [0-7.84] ng/ml in EDM without LM; and were undetectable in most cases of benign meningeal diseases and non-EDM with LM. The cut-off values of 0.22 ng/ml for methylated cfSHP1P2 and 0.59 ng/ml for wSHP1P2 were the best to discriminate EDM with LM from EDM without LM (sensitivity: 79-100 %; specificity: 83-100 %), as well as from other benign conditions (sensitivity: 85-100 % specificity: 78 100 %). CSF cytology yielded 76 % sensitivity for diagnosing EDM with LM. Further validation of CSF SHP1P2 methylation detection as a role of adjunctive tool for LM from EDM should be interested based on our study. PMID- 27401154 TI - Impact of gross total resection in patients with WHO grade III glioma harboring the IDH 1/2 mutation without the 1p/19q co-deletion. AB - The prognosis of patients with WHO grade III gliomas is highly dependent on their genomic status such as the isocitrate dehydrogenase (IDH) 1/2 mutation and1p/19q co-deletion. However, difficulties have been associated with determining which tumors have certain genomic profiles by preoperative radiographical modalities, and the role of surgical resection in achieving better outcomes remains unclear. This retrospective study included 124 consecutive patients with newly diagnosed grade III gliomas. The genomic status of IDH1/2 and 1p/19q was analyzed in these patients. Tumors were then divided into 3 subgroups based on their genomic status; the IDH 1/2 mutation with the 1p/19q co-deletion (1p/19q co-del), the IDH 1/2 mutation without the 1p/19q co-deletion (non-1p/19q co-del), and the IDH 1/2 wild type (IDH wt). Survival times were compared between patients who underwent gross total resection and those who did not (GTR versus non-GTR). The relationships between genomic statuses and MR imaging characteristics such as ring-like or nodular enhancements by gadolinium, and very low intensity on T1 weighted images with blurry enhancements (T1VL) were also examined. Among all patients with grade III gliomas, GTR patients had longer median survival and progression-free times than those of non-GTR patients (undefined versus 87 months, p = 0.097, and 124 versus 34 months, p = 0.059, respectively). No significant differences were observed in survival between GTR and non-GTR patients in the 1p/19q co-del group (p = 0.14), or between GTR and non-GTR patients in the IDH wt group (26 and 27 months, p = 0.29). On the other hand, in non-1p/19q co-del group, survival was significantly longer in GTR patients than in non-GTR patients (undefined versus 77 months, p = 0.005). Radiographically, T1VL was detected in most tumors in the non-1p/19q co-del group (78.2 %), but only 6 (21.4 %) and 17 (41.5 %) tumors in the 1p/19q co-del and IDH wt groups, respectively. A correlation was not found between other genomic subgroups and MR imaging findings. Strict surgical removal is important to improve the prognosis of patients with grade III gliomas, especially for tumors with the IDH 1/2 mutation without the 1p/19q co-deletion. The MR finding of T1VL can be used to select candidates for more radical resection. PMID- 27401155 TI - Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy. AB - To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were <= 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income >=$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving >=59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease. PMID- 27401156 TI - Prognostic value of the S100B protein in newly diagnosed and recurrent glioma patients: a serial analysis. AB - The S100B protein is associated with brain damage and a breached blood-brain barrier. A previous pilot study showed that high serum levels of S100B are associated with shorter survival in glioma patients. The aim of our study was to assess the prognostic value in terms of survival and longitudinal dynamics of serum S100B for patients with newly diagnosed and recurrent glioma. We obtained blood samples from patients with newly diagnosed and recurrent glioma before the start (baseline) and at fixed time-points during temozolomide chemotherapy. S100B data were dichotomized according to the upper limit of the reference value of 0.1 MUg/L. Overall survival (OS) was estimated with Kaplan-Meier curves and groups were compared with the log rank analysis. To correct for potential confounders a Cox regression analysis was used. We included 86 patients with newly-diagnosed and 27 patients with recurrent glioma. Most patients in both groups had baseline serum levels within normal limits. In the newly diagnosed patients we found no significant difference in OS between the group of patients with S100B levels >0.1 MUg/L at baseline compared to those with <0.1 MUg/L. In the patients with recurrent glioma we found a significantly shorter OS for patients with raised levels. In both groups, S100B values did not change significantly throughout the course of the disease. Serum S100B levels do not seem to have prognostic value in newly diagnosed glioma patients. In recurrent glioma patients S100B might be of value in terms of prognostication of survival. PMID- 27401157 TI - Coexistence of MLH3 germline variants in colon cancer patients belonging to families with Lynch syndrome-associated brain tumors. PMID- 27401158 TI - Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients. AB - The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income >=$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease. PMID- 27401159 TI - Corn forage biological pretreatment by Trametes versicolor in a tray bioreactor. AB - Trametes versicolor is a white-rot fungus known to be efficient in lignin removal due to its complex extracellular lignocellulolytic enzymatic system. Therefore, it can be used in the treatment of lignocellulose waste from agro, food, and wood industries. In a first experiment, corn forage treatment with T. versicolor was investigated in laboratory jars. In a second experiment, the process was scaled up to a tray bioreactor. In the tray bioreactor, the process of lignin degradation was improved, resulting in an increase in lignin conversion of up to 71% during seven days' treatment. PMID- 27401160 TI - Effect of pyrolysis conditions on the characteristics of biochar produced from a tobacco stem. AB - To investigate the potential use of tobacco stems as feedstock for biochar production, a variety of pyrolysis conditions were studied to determine their effects on the distribution of pyrolysis products, as well as the physicochemical properties, energy yield and porosity characteristics of the biochar. The results showed that a moderate temperature of 400-450 degrees C, a retention time of three hours and a slow heating rate of 5 degrees C min(-1) was better to get high energy yield from biochar. In this study, the highest calorific value of biochar was 28.128 MJ kg(-1) The highest biochar yield occurred at a moderate retention time of three hours. The heating rate had an important influence on the characteristics of biochar, and the physiochemical properties of biochar produced at a heating rate of 10 degrees C min(-1) were better than other levels. Also, the oil yield decreased and gas yield increased as retention time and heating rate increased. Biochar produced at a high temperature of 600 degrees C, a retention time up to four hours and a heating rate of 10-15 degrees C min(-1) had a larger BET surface area and cumulative pore volume than that of others. The highest change rate of pore volume of biochar almost occurred at the pore size of 2-5 nm. PMID- 27401161 TI - Estimation of methane emission flux at landfill surface using laser methane detector: Influence of gauge pressure. AB - The aim of this study was to investigate the possibility of measuring methane emission fluxes, using surface methane concentration and gauge pressure, by analyzing the influence of gauge pressure on the methane emission flux and the surface methane concentration, as well as the correlation between the methane emission flux and surface methane concentrations. The surface methane concentration was measured using a laser methane detector. Our results show a positive linear relationship between the surface methane concentration and the methane emission flux. Furthermore, the methane emission flux showed a positive linear relationship with the gauge pressure; this implies that when the surface methane concentration and the surface gauge pressure are measured simultaneously, the methane emission flux can be calculated using Darcy's law. A decrease in the vertical permeability was observed when the gauge pressure was increased, because reducing the vertical permeability may lead to a reduced landfill gas emission to the atmosphere, and landfill gas would be accumulated inside the landfill. Finally, this method is simple and can allow for a greater number of measurements during a relatively shorter period. Thus, it provides a better representation of the significant space and time variations in methane emission fluxes. PMID- 27401162 TI - Calculating the costs of waste collection: A methodological proposal. AB - Waste collection and transport can generate up to 70% of the total costs of the system. Separated collection of recyclables implies additional costs for which the sale of recycled waste often does not compensate, but there is increased pressure to reach the long-term recycling objectives set by law. The proper estimation and monitoring of waste collection costs are essential to define the most cost-effective waste collection system. The aim of this study is to propose and implement a management tool to determine waste collection costs for different waste collection schemes. Based on input data, such as waste quantity and composition, the number of waste bins, the location of collection points, the type of collection vehicle, crew, collection route, etc., the developed tool can calculate the time and costs of waste collection (per vehicle, collection point or tonne of collected waste). This tool uses Excel spreadsheets and it was tested on a district in the central area of the city of Kragujevac to calculate the costs of waste collection for two scenarios: Collecting all waste as mixed waste, and collecting separately recyclables and residual waste. The developed tool can be useful for municipal solid waste management companies, since it allows benchmarking and variance analysis. PMID- 27401163 TI - Health literacy in pregnant women facing prenatal screening may explain their intention to use a patient decision aid: a short report. AB - BACKGROUND: It has been suggested that health literacy may impact the use of decision aids (DAs) among patients facing difficult decisions. Embedded in the pilot test of a questionnaire, this study aimed to measure the association between health literacy and pregnant women's intention to use a DA to decide about prenatal screening. We recruited a convenience sample of 45 pregnant women in three clinical sites (family practice teaching unit, birthing center and obstetrical ambulatory care clinic). We asked participating women to complete a self-administered questionnaire assessing their intention to use a DA to decide about prenatal screening and assessed their health literacy levels using one subjective and two objective scales. RESULTS: Two of the three scales discriminated between levels of health literacy (three numeracy questions and three health literacy questions). We found a positive correlation between pregnant women's intention to use a DA and subjective health literacy (Spearman coefficient, Rho 0.32, P = 0.04) but not objective health literacy (Spearman coefficient, Rho 0.07, P = 0.65). Hence subjective health literacy may affect the intention to use a DA among pregnant women facing a decision about prenatal screening. CONCLUSION: Special attention should be given to pregnant women with lower health literacy levels to increase their intention to use a DA and ensure that every pregnant women can give informed and value-based consent to prenatal screening. PMID- 27401164 TI - Opportunities for Integrating Physical Health Within Assertive Community Treatment Teams: Results from Practitioner Focus Groups. AB - This qualitative study assessed the experiences of assertive community treatment (ACT) team members regarding the integration of physical and mental health self management for persons with serious mental illness. Three focus groups elicited information from participants concerning barriers, strategies, and recommendations. Findings from inductive analyses revealed six overarching themes: (1) collaboration with primary care, (2) improvements in engagement, (3) team-focused roles, (4) education and training, (5) recommendations for system level barriers, and (6) systems collaboration. Participant recommendations suggest that ACT teams are well positioned to integrate mental and physical health treatment, but further research is needed to support integrated care. PMID- 27401165 TI - Access to Secondary Mental Health Services in a Cohort of New Zealand Mothers. AB - To explore access to secondary mental health services for New Zealand women during pregnancy and for up to 1 year post-delivery. A retrospective cohort analysis of public hospital maternity data linked to mental health collections. 27 in 1000 pregnancies were associated with access to secondary mental health services (736/27,153). Independent of ethnicity, young age (<20 years) was associated with access (RR1.84; 95 %CI 1.42-2.38; P < .0001). Smoking (1.48; 1.24 1.78; P < .0001), alcohol (1.3; 0.97-1.71; P < .0001) and substance use (3.57; 2.61-4.88; P < .0001) during pregnancy were independent risk factors associated with access. Antenatal period provides an opportunity for navigating to services to ensure timely access to secondary mental health services. PMID- 27401166 TI - Alveolar Rhabdomyosarcoma of the foot metastasizing to the Iris: report of a rare case. AB - BACKGROUND: Intraocular iris rhabdomyosarcoma is extremely rare, and in the 3 cases reported to date occurred as the primary site of tumour growth. We report a case of rhabdomyosarcoma of the foot metastasizing to the iris. CASE PRESENTATION: An 18-year-old white female was referred to the London Ocular Oncology Service for management of a metastatic rhabdomyosarcomatous deposit in the iris, a metastasis from alveolar rhabdomyosarcoma of the foot. She was diagnosed nearly 2 years earlier with the primary sarcoma with extensive systemic spread and treated by resection of the foot lesion and chemotherapy, and achieved a partial remission. The left iris deposit was noted while she was receiving systemic chemotherapy, heralding a relapse. However, anterior uveitis and raised intraocular pressure developed and she was referred to our service for further management. A left iris secondary rhabdomyosarcoma deposit was noticed and in addition a lacrimal gland mass, as indicated by ultrasound B scan of the eye and orbit. The patient was treated with external beam radiotherapy to the globe and orbit, but died 2 months after treatment completion. CONCLUSION: Rhabdomyosarcoma of the iris is very rare and was previously documented only as a primary malignancy in this location. We report that secondary spread to the iris can also occur, in this case as the first sign of widely disseminated systemic relapse. PMID- 27401167 TI - Searching for the Prosocial Personality: A Big Five Approach to Linking Personality and Prosocial Behavior. AB - The search for the prosocial personality has been long and controversial. The current research explores the general patterns underlying prosocial decisions, linking personality, emotion, and overt prosocial behavior. Using a multimethod approach, we explored the links between the Big Five dimensions of personality and prosocial responding. Across three studies, we found that agreeableness was the dimension of personality most closely associated with emotional reactions to victims in need of help, and subsequent decisions to help those individuals. Results suggest that prosocial processes, including emotions, cognitions, and behaviors, may be part of a more general motivational process linked to personality. PMID- 27401168 TI - Five ways the UK clinical academic workforce is changing. PMID- 27401169 TI - Evaluation of the Tobii EyeX Eye tracking controller and Matlab toolkit for research. AB - The Tobii Eyex Controller is a new low-cost binocular eye tracker marketed for integration in gaming and consumer applications. The manufacturers claim that the system was conceived for natural eye gaze interaction, does not require continuous recalibration, and allows moderate head movements. The Controller is provided with a SDK to foster the development of new eye tracking applications. We review the characteristics of the device for its possible use in scientific research. We develop and evaluate an open source Matlab Toolkit that can be employed to interface with the EyeX device for gaze recording in behavioral experiments. The Toolkit provides calibration procedures tailored to both binocular and monocular experiments, as well as procedures to evaluate other eye tracking devices. The observed performance of the EyeX (i.e. accuracy < 0.6 degrees , precision < 0.25 degrees , latency < 50 ms and sampling frequency ~55 Hz), is sufficient for some classes of research application. The device can be successfully employed to measure fixation parameters, saccadic, smooth pursuit and vergence eye movements. However, the relatively low sampling rate and moderate precision limit the suitability of the EyeX for monitoring micro saccadic eye movements or for real-time gaze-contingent stimulus control. For these applications, research grade, high-cost eye tracking technology may still be necessary. Therefore, despite its limitations with respect to high-end devices, the EyeX has the potential to further the dissemination of eye tracking technology to a broad audience, and could be a valuable asset in consumer and gaming applications as well as a subset of basic and clinical research settings. PMID- 27401170 TI - National survey of pellucid marginal corneal degeneration in Japan. AB - PURPOSE: A national survey was conducted in Japan to analyze the clinical characteristics of pellucid marginal corneal degeneration (PMD). METHODS: A questionnaire was sent to all members of the Japan Cornea Society requesting demographic and clinical findings on PMD patients who had been examined between 2008 and 2010. The presence of band-shaped peripheral corneal thinning, detected by slit-lamp biomicroscopy or by a pachymetric map, was set as the diagnostic criterion of PMD. RESULTS: Most of the participating facilities relied on either slit-lamp biomicroscopy or corneal topography as diagnostic tools for the detection of PMD. Data on 347 patients (579 eyes) were returned from the participating facilities for analysis, among which 162 eyes in 84 men and 24 women, with a median onset age of 37 years, met the PMD criteria. Of the 108 patients (162 eyes) with classical PMD, unilateral involvement was found in 25 % of patients (27 eyes). In 17 of the 27 eyes for which topographic findings for the contralateral eye were available, seven eyes were either keratoconus or had a suspected diagnosis of keratoconus. An association with allergic disease was found in 24 eyes (22.2 % of patients). Approximately half of the patients had 1.0 or better spectacle-corrected distance visual acuity, and only 5 % showed 0.1 or worse. The mean keratometric value was 45.7 diopters. On corneal topography, 100 eyes (61.7 %) showed the topographic "crab-claw pattern," and the remaining eyes showed other patterns, including inferior steepening (22.2 %) and an irregular pattern (10.5 %). CONCLUSIONS: We conducted the largest clinical survey of PMD to date and found a male predominance, a relatively high prevalence of unilateral involvement, and associated allergic diseases. PMID- 27401171 TI - Uncovering the liver's role in immunity through RNA co-expression networks. AB - Gene co-expression analysis has proven to be a powerful tool for ascertaining the organization of gene products into networks that are important for organ function. An organ, such as the liver, engages in a multitude of functions important for the survival of humans, rats, and other animals; these liver functions include energy metabolism, metabolism of xenobiotics, immune system function, and hormonal homeostasis. With the availability of organ-specific transcriptomes, we can now examine the role of RNA transcripts (both protein coding and non-coding) in these functions. A systems genetic approach for identifying and characterizing liver gene networks within a recombinant inbred panel of rats was used to identify genetically regulated transcriptional networks (modules). For these modules, biological consensus was found between functional enrichment analysis and publicly available phenotypic quantitative trait loci (QTL). In particular, the biological function of two liver modules could be linked to immune response. The eigengene QTLs for these co-expression modules were located at genomic regions coincident with highly significant phenotypic QTLs; these phenotypes were related to rheumatoid arthritis, food preference, and basal corticosterone levels in rats. Our analysis illustrates that genetically and biologically driven RNA-based networks, such as the ones identified as part of this research, provide insight into the genetic influences on organ functions. These networks can pinpoint phenotypes that manifest through the interaction of many organs/tissues and can identify unannotated or under-annotated RNA transcripts that play a role in these phenotypes. PMID- 27401172 TI - Novel Insights into Chromosome Evolution in Birds, Archosaurs, and Reptiles. AB - Homologous synteny blocks (HSBs) and evolutionary breakpoint regions (EBRs) in mammalian chromosomes are enriched for distinct DNA features, contributing to distinct phenotypes. To reveal HSB and EBR roles in avian evolution, we performed a sequence-based comparison of 21 avian and 5 outgroup species using recently sequenced genomes across the avian family tree and a newly-developed algorithm. We identified EBRs and HSBs in ancestral bird, archosaurian (bird, crocodile, and dinosaur), and reptile chromosomes. Genes involved in the regulation of gene expression and biosynthetic processes were preferably located in HSBs, including for example, avian-specific HSBs enriched for genes involved in limb development. Within birds, some lineage-specific EBRs rearranged genes were related to distinct phenotypes, such as forebrain development in parrots. Our findings provide novel evolutionary insights into genome evolution in birds, particularly on how chromosome rearrangements likely contributed to the formation of novel phenotypes. PMID- 27401173 TI - SENCA: A Multilayered Codon Model to Study the Origins and Dynamics of Codon Usage. AB - Gene sequences are the target of evolution operating at different levels, including the nucleotide, codon, and amino acid levels. Disentangling the impact of those different levels on gene sequences requires developing a probabilistic model with three layers. Here we present SENCA (site evolution of nucleotides, codons, and amino acids), a codon substitution model that separately describes 1) nucleotide processes which apply on all sites of a sequence such as the mutational bias, 2) preferences between synonymous codons, and 3) preferences among amino acids. We argue that most synonymous substitutions are not neutral and that SENCA provides more accurate estimates of selection compared with more classical codon sequence models. We study the forces that drive the genomic content evolution, intraspecifically in the core genome of 21 prokaryotes and interspecifically for five Enterobacteria. We retrieve the existence of a universal mutational bias toward AT, and that taking into account selection on synonymous codon usage has consequences on the measurement of selection on nonsynonymous substitutions. We also confirm that codon usage bias is mostly driven by selection on preferred codons. We propose new summary statistics to measure the relative importance of the different evolutionary processes acting on sequences. PMID- 27401174 TI - Transcriptomics of Intralocus Sexual Conflict: Gene Expression Patterns in Females Change in Response to Selection on a Male Secondary Sexual Trait in the Bulb Mite. AB - Intralocus sexual conflict (IASC) prevents males and females from reaching their disparate phenotypic optima and is widespread, but little is known about its genetic underpinnings. In Rhizoglyphus robini, a mite species with alternative male morphs, elevated sexual dimorphism of the armored fighter males (compared to more feminized scramblers males) was previously reported to be associated with increased IASC. Because IASC persists if gene expression patterns are correlated between sexes, we compared gene expression patterns of males and females from the replicate lines selected for increased proportion of fighter or scrambler males (F- and S-lines, respectively). Specifically, we tested the prediction that selection for fighter morph caused correlated changes in gene expression patterns in females. We identified 532 differentially expressed genes (FDR < 0.05) between the F-line and S-line males. Consistent with the prediction, expression levels of these genes also differed between females from respective lines. Thus, significant proportion of genes differentially expressed between sexually selected male phenotypes showed correlated expression levels in females, likely contributing to elevated IASC in F-lines reported in a previous study. PMID- 27401175 TI - Genes Translocated into the Plastid Inverted Repeat Show Decelerated Substitution Rates and Elevated GC Content. AB - Plant chloroplast genomes (plastomes) are characterized by an inverted repeat (IR) region and two larger single copy (SC) regions. Patterns of molecular evolution in the IR and SC regions differ, most notably by a reduced rate of nucleotide substitution in the IR compared to the SC region. In addition, the organization and structure of plastomes is fluid, and rearrangements through time have repeatedly shuffled genes into and out of the IR, providing recurrent natural experiments on how chloroplast genome structure can impact rates and patterns of molecular evolution. Here we examine four loci (psbA, ycf2, rps7, and rps12 exon 2-3) that were translocated from the SC into the IR during fern evolution. We use a model-based method, within a phylogenetic context, to test for substitution rate shifts. All four loci show a significant, 2- to 3-fold deceleration in their substitution rate following translocation into the IR, a phenomenon not observed in any other, nontranslocated plastid genes. Also, we show that after translocation, the GC content of the third codon position and of the noncoding regions is significantly increased, implying that gene conversion within the IR is GC-biased. Taken together, our results suggest that the IR region not only reduces substitution rates, but also impacts nucleotide composition. This finding highlights a potential vulnerability of correlating substitution rate heterogeneity with organismal life history traits without knowledge of the underlying genome structure. PMID- 27401176 TI - On the Origin of De Novo Genes in Arabidopsis thaliana Populations. AB - De novo genes, which originate from ancestral nongenic sequences, are one of the most important sources of protein-coding genes. This origination process is crucial for the adaptation of organisms. However, how de novo genes arise and become fixed in a population or species remains largely unknown. Here, we identified 782 de novo genes from the model plant Arabidopsis thaliana and divided them into three types based on the availability of translational evidence, transcriptional evidence, and neither transcriptional nor translational evidence for their origin. Importantly, by integrating multiple types of omics data, including data from genomes, epigenomes, transcriptomes, and translatomes, we found that epigenetic modifications (DNA methylation and histone modification) play an important role in the origination process of de novo genes. Intriguingly, using the transcriptomes and methylomes from the same population of 84 accessions, we found that de novo genes that are transcribed in approximately half of the total accessions within the population are highly methylated, with lower levels of transcription than those transcribed at other frequencies within the population. We hypothesized that, during the origin of de novo gene alleles, those neutralized to low expression states via DNA methylation have relatively high probabilities of spreading and becoming fixed in a population. Our results highlight the process underlying the origin of de novo genes at the population level, as well as the importance of DNA methylation in this process. PMID- 27401177 TI - The Transcriptomic Evolution of Mammalian Pregnancy: Gene Expression Innovations in Endometrial Stromal Fibroblasts. AB - The endometrial stromal fibroblast (ESF) is a cell type present in the uterine lining of therian mammals. In the stem lineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation. We call the latter cell type "neo-ESF" in contrast to "paleo-ESF" which is homologous to eutherian ESF but is not able to decidualize. In this study, we compare the transcriptomes of ESF from six therian species: Opossum (Monodelphis domestica; paleo-ESF), mink, rat, rabbit, human (all neo-ESF), and cow (secondarily nondecidualizing neo-ESF). We find evidence for strong stabilizing selection on transcriptome composition suggesting that the expression of approximately 5,600 genes is maintained by natural selection. The evolution of neo-ESF from paleo-ESF involved the following gene expression changes: Loss of expression of genes related to inflammation and immune response, lower expression of genes opposing tissue invasion, increased markers for proliferation as well as the recruitment of FOXM1, a key gene transiently expressed during decidualization. Signaling pathways also evolve rapidly and continue to evolve within eutherian lineages. In the bovine lineage, where invasiveness and decidualization were secondarily lost, we see a re-expression of genes found in opossum, most prominently WISP2, and a loss of gene expression related to angiogenesis. The data from this and previous studies support a scenario, where the proinflammatory paleo-ESF was reprogrammed to express anti-inflammatory genes in response to the inflammatory stimulus coming from the implanting conceptus and thus paving the way for extended, trans-cyclic gestation. PMID- 27401178 TI - Neurogenic lower urinary tract dysfunction: evaluation and management. AB - The lower urinary tract (LUT) in health is regulated by coordinated multi-level neurological inputs which require an intact central and peripheral nervous system. Lower urinary tract dysfunction is, therefore, a common sequelae of neurological disease and the patterns of bladder storage and voiding dysfunction depend upon the level of neurological lesion. Evaluation includes history taking, bladder diary, urological examination when relevant, ultrasonography and urodynamic testing when indicated. Antimuscarinic agents are the first line treatment for patients with storage dysfunction. Alternative treatments include intradetrusor injection of onabotulinumtoxinA, which has been shown to be of benefit in patients with neurogenic detrusor overactivity (NDO), and neuromodulation. Intermittent catheterization remains the option of choice in patients with significant voiding dysfunction resulting in high post-void residual volumes. PMID- 27401180 TI - The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers. AB - Background: Healthy people with a family history of alcohol problems show a pattern of subjective responses to alcohol that resemble those of affected probands. Studies on ketamine suggest that up-regulation of N-methyl-D-aspartate receptors (NMDARs) underlies these effects, and point to a pharmacologically responsive endophenotype reflecting enhanced risk for alcohol-use disorders. Methods: Subjective stimulant and sedative effects were assessed before and during nitrous oxide (N2O; 50%) inhalation in heavy drinkers who were otherwise healthy. Results: Participants with an ostensible family history of alcohol-use disorders (n = 23) were distinguishable from those without such familial risk (n = 37) by an enhanced stimulation-to-sedation ratio during N2O inhalation. Conclusion: The pattern of subjective effects of N2O according to familial risk is remarkably similar to that previously seen with ketamine, supporting the idea of a common, NMDAR-mediated mechanism of action. N2O may prove to be a safe and accessible alternative to ketamine for probing heritable NMDAR dysregulation in neuropsychiatric disorders. PMID- 27401182 TI - Michel Gagner-Biography. PMID- 27401181 TI - Mini dental assessment: a simple screening test for non-dental staff. AB - OBJECTIVE: The objective of this study was to develop a simple tool for the assessment of possible dental treatment needs (DTN) for non-dental professionals (Mini Dental Assessment, MDA). To keep the assessment universal, we aimed to base it on the patient's history and a simple chewing efficiency test (CET) as the dental status is a known determinant for chewing efficiency. MATERIALS & METHODS: The assessment was developed using data from 169 patients from two sites (University Hospital Giessen, St. Bonifatius Hospital Lingen, both Germany). In all patients, a dental examination was performed, the denture status was evaluated (based on the California Dental Association criteria; CDA criteria), and the DTN was determined. In addition, the time since the patient's last visit to a dentist (TLVD) and denture age (DA) were assessed. Furthermore, a CET was carried out and the comminution score was determined (CETS). RESULTS: In total, 108 patients required dental treatment. The mean value (+/-SD) was 2.9 +/- 0.9 score points for the DTN, 2.5 +/- 3.8 years for the TLVD, and 10.8 +/- 8.9 years for the DA. There was a significant correlation (Spearman, P < .05) between the DTN and degree of comminution (3.4 +/- 1.8). Based on the results of the statistical analysis, the intended assessment tool was developed using the variables CETS, TLVD, and DA weighed by their respective regression coefficients (10:3:1). Subsequently, the resulting MDA score (51.32 +/- 28.14) was calculated. A sensitivity/specificity analysis was conducted and a receiver operating characteristic curve was calculated (SPSS 17.0, area under curve 0.805; 95 % CI 0.738-0.873). CONCLUSION: It can be concluded that the dental status of elderly patients is reflected in the outcome of the MDA. However, ongoing validation is needed. TRIAL REGISTRATION: DRKS00003219. PMID- 27401183 TI - Low Educational Status and Childhood Obesity Associated with Insufficient Mid Term Weight Loss After Sleeve Gastrectomy: a Retrospective Observational Cohort Study. AB - PURPOSE: Successful weight loss after bariatric surgery has been associated with a variety of factors. The aim of this study was to determine the effects of educational status on surgical weight loss for patients undergoing sleeve gastrectomy (SG). MATERIALS AND METHODS: This retrospective cohort study was carried out on patients undergoing SG between September 2013 and July 2015. Six months after surgery, the patients were classified into two groups according to their success in the percentage of excess weight loss (%EWL). Group 1: <%50EWL (insufficient WL) and group 2: >=%50EWL (successful WL) in the sixth month. The independent predictors for insufficient weight loss six months after SG were analyzed. RESULTS: In the sixth post-operative month, their mean %EWL and percentage of excess body mass index loss (%EBMIL) were 50 +/- 15.4 and 58.2 +/- 19.3, respectively. In univariate analysis, group 1 patients were found to be significantly older when compared to group 2 patients while the education level of group 2 patients was significantly higher when compared to group 1. A tertiary educational level at a university or higher was associated with a nearly fourfold increased success in weight loss (AOR 3.772, p = 0.03) 6 months after SG. Multivariate analysis showed that patients with a history of childhood obesity were more likely to have insufficient weight loss (AOR 0.390, p = 0.045). CONCLUSION: Childhood obesity and a lower level of education are associated with insufficient weight loss 6 months after SG. However, prospective external validation is warranted, with a long-term follow-up of a large bariatric surgery population. PMID- 27401179 TI - Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases. AB - The implementation of a variety of immunosuppressive therapies has made drug associated progressive multifocal leukoencephalopathy (PML) an increasingly prevalent clinical entity. The purpose of this study was to investigate its diagnostic characteristics and to determine whether differences herein exist between the multiple sclerosis (MS), neoplasm, post-transplantation, and autoimmune disease subgroups. Reports of possible, probable, and definite PML according to the current diagnostic criteria were obtained by a systematic search of PubMed and the Dutch pharmacovigilance database. Demographic, epidemiologic, clinical, radiological, cerebrospinal fluid (CSF), and histopathological features were extracted from each report and differences were compared between the disease categories. In the 326 identified reports, PML onset occurred on average 29.5 months after drug introduction, varying from 14.2 to 37.8 months in the neoplasm and MS subgroups, respectively. The most common overall symptoms were motor weakness (48.6 %), cognitive deficits (43.2 %), dysarthria (26.3 %), and ataxia (24.1 %). The former two also constituted the most prevalent manifestations in each subgroup. Lesions were more often localized supratentorially (87.7 %) than infratentorially (27.4 %), especially in the frontal (64.1 %) and parietal lobes (46.6 %), and revealed enhancement in 27.6 % of cases, particularly in the MS (42.9 %) subgroup. Positive JC virus results in the first CSF sample were obtained in 63.5 %, while conversion after one or more negative outcomes occurred in 13.7 % of cases. 52.2 % of patients died, ranging from 12.0 to 83.3 % in the MS and neoplasm subgroups, respectively. In conclusion, despite the heterogeneous nature of the underlying diseases, motor weakness and cognitive changes were the two most common manifestations of drug-associated PML in all subgroups. The frontal and parietal lobes invariably constituted the predilection sites of drug related PML lesions. PMID- 27401184 TI - Risk factors for mortality in patients admitted to intensive care units with pneumonia. AB - BACKGROUND: Despite the high mortality in patients with pneumonia admitted to an ICU, data on risk factors for death remain limited. METHODS: In this secondary analysis of PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial), we focused on the patients admitted to ICU with a primary diagnosis of pneumonia. The primary outcome for this study was 90-day hospital mortality and the secondary outcome was 90-day ICU mortality. Cox regression model was conducted to examine the relationship between baseline and time-dependent variables and hospital and ICU mortality. RESULTS: Six hundred sixty seven patients admitted with pneumonia (43.8 % females) were included in our analysis, with a mean age of 60.7 years and mean APACHE II score of 21.3. During follow-up, 111 patients (16.6 %) died in ICU and in total, 149 (22.3 %) died in hospital. Multivariable analysis demonstrated significant independent risk factors for hospital mortality including male sex (hazard ratio (HR) = 1.5, 95 % confidence interval (CI): 1.1 - 2.2, p-value = 0.021), higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p value < 0.001 for per-5 point increase), chronic heart failure (HR = 2.9, 95 % CI: 1.6 - 5.4, p-value = 0.001), and dialysis (time-dependent effect: HR = 2.7, 95 % CI: 1.3 - 5.7, p-value = 0.008). Higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p-value = 0.002 for per-5 point increase) and chronic heart failure (HR = 2.6, 95 % CI: 1.3 - 5.0, p-value = 0.004) were significantly related to risk of death in the ICU. CONCLUSION: In this study using data from a multicenter thromboprophylaxis trial, we found that male sex, higher APACHE II score on admission, chronic heart failure, and dialysis were independently associated with risk of hospital mortality in patients admitted to ICU with pneumonia. While high illness severity score, presence of a serious comorbidity (heart failure) and need for an advanced life support (dialysis) are not unexpected risk factors of mortality, male sex might necessitate further exploration. More studies are warranted to clarify the effect of these risk factors on survival in critically ill patients admitted to ICU with pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182143 . PMID- 27401185 TI - Feasibility of Singlet Analysis for Ligand Binding Assays: a Retrospective Examination of Data Generated Using the Gyrolab Platform. AB - There are many sources of analytical variability in ligand binding assays (LBA). One strategy to reduce variability has been duplicate analyses. With recent advances in LBA technologies, it is conceivable that singlet analysis is possible. We retrospectively evaluated singlet analysis using Gyrolab data. Relative precision of duplicates compared to singlets was evaluated using 60 datasets from toxicokinetic (TK) or pharmacokinetic (PK) studies which contained over 23,000 replicate pairs composed of standards, quality control (QC), and animal samples measured with 23 different bioanalytical assays. The comparison was first done with standard curve and QCs followed by PK parameters (i.e., Cmax and AUC). Statistical analyses were performed on combined duplicate versus singlets using a concordance correlation coefficient (CCC), a measurement used to assess agreement. Variance component analyses were conducted on PK estimates to assess the relative analytical and biological variability. Overall, 97.5% of replicate pairs had a %CV of <11% and 50% of the results had a %CV of <=1.38%. There was no observable bias in concentration comparing the first replicate with the second (CCC of 0.99746 and accuracy value of 1). The comparison of AUC and Cmax showed no observable difference between singlet and duplicate (CCC for AUC and Cmax >0.99999). Analysis of variance indicated an AUC inter-subject variability 35.3-fold greater than replicate variability and 8.5-fold greater for Cmax. Running replicates from the same sample will not significantly reduce variation or change PK parameters. These analyses indicated the majority of variance was inter-subject and supported the use of a singlet strategy. PMID- 27401186 TI - Synergistic estrogenic effects of Fusarium and Alternaria mycotoxins in vitro. AB - Mycotoxins are toxic secondary metabolites formed by various fungal species that are found as natural contaminants in food. This very heterogeneous group of compounds triggers multiple toxic mechanisms, including endocrine disruptive potential. Current risk assessment of mycotoxins, as for most chemical substances, is based on the effects of single compounds. However, concern on a potential enhancement of risks by interactions of single substances in naturally occurring mixtures has greatly increased recently. In this study, the combinatory effects of three mycoestrogens were investigated in detail. This includes the endocrine disruptors zearalenone (ZEN) and alpha-zearalenol (alpha-ZEL) produced by Fusarium fungi and alternariol (AOH), a cytotoxic and estrogenic mycotoxin formed by Alternaria species. For evaluation of effects, estrogen-dependent activation of alkaline phosphatase (AlP) and cell proliferation were tested in the adenocarcinoma cell line Ishikawa. The estrogenic potential varied among the single substances. Half maximum effect concentrations (EC50) for AlP activation were evaluated for alpha-ZEL, ZEN and AOH as 37 pM, 562 pM and 995 nM, respectively. All three mycotoxins were found to act as partial agonists. The majority of binary combinations, even at very low concentrations in the case of alpha-ZEL, showed strong synergism in the AlP assay. These potentiating phenomena of mycotoxin mixtures highlight the urgent need to incorporate combinatory effects into future risk assessment, especially when endocrine disruptors are involved. To the best of our knowledge, this study presents the first investigation on synergistic effects of mycoestrogens. PMID- 27401187 TI - Effect of antenatal depression on maternal dietary intake and neonatal outcome: a prospective cohort. AB - BACKGROUND: In Pakistan, incidence of antenatal depression ranges from 18 to 80 %, which goes undiagnosed, resulting in maternal and neonatal implications. The current study aimed to examine the association of antenatal depression with maternal dietary intake and neonatal outcome. METHODS: A hospital-based, prospective cohort study was conducted on 94 middle class antenatal attendees coming to a tertiary care hospital in Lahore, Pakistan at the beginning of second trimester. Participants fulfilling eligibility were enrolled consecutively after taking written informed consent. Exposure group was identified by Edinburgh Postnatal Depression Scale (EPDS) and cohort members were followed till after delivery. Maternal dietary intake was assessed by 24-h Recall and Food Frequency Checklist, while neonatal outcome was identified through patient files before discharge. Data on potential confounders was collected. Loss to follow up was 13 % (82/94). Data was collected from April-September 2013. Results for 82 participants were analyzed using SPSS version 21. RESULTS: EPDS screened 35/82 (43 %) eligible antenatal attendees as depressed, out of which 16/35 (20 %) were severely depressed and 19/35 (23 %) were moderately depressed. Incidence of poor maternal dietary intake was more in females with antenatal depression. Antenatal depression increased the risk of poor Healthy Eating Index (RR = 2.58, C.I 1.60 5.23, AR = 62 %), carbohydrate <175 gm (RR = 1.188, CI 0.836-1.688, AR = 15 %), protein <71 gm (RR = 1.343, CI 1.059-1.703, AR = 26 %) and fat <55 gm (RR = 2.954, CI 1.612-5.416, AR = 67 %) Incidence of neonatal outcomes included, Fetal Growth Retardation (RR = 2.70, C.I 0.69-3.70, AR = 60 %), preterm birth (RR = 1.60, C.I 0.72-2.45, AR = 54 %), low Apgar score (RR = 2.70, C.I 0.69-3.70, AR = 60 %) and Low Birth Weight (RR = 0.56, C.I 0.93-1.39, AR = -44 %). CONCLUSION: Antenatal women with depression developed poor dietary intake and had increased incidence of Fetal Growth Retardation, preterm birth and low Apgar score, but not of Low Birth Weight. PMID- 27401189 TI - Fluorometric cell-based assay for beta-galactosidase activity in probiotic gram positive bacterial cells - Lactobacillus helveticus. AB - Although methods for measuring beta-galactosidase activity in intact gram negative bacterial cells have been reported, the methods may not be applicable to measuring beta-galactosidase activity in gram-positive bacterial cells. This report focuses on the development of a fluorometric cell-based assay for measuring beta-galactosidase activity in gram-positive cells. PMID- 27401188 TI - Is there a relation between pre-sarcopenia, sarcopenia, cachexia and osteoporosis in patients with ankylosing spondylitis? AB - BACKGROUND: Osteoporosis is a well-known complication of ankylosing spondylitis (AS). However, data about body composition modifications and muscle performance showed conflicting results. The aim of the study was to determine the prevalence and risk factors of pre-sarcopenia, sarcopenia and cachexia in patients with AS and analyze its relationship with bone loss and symptomatic and severity parameters of the disease. METHODS: Sixty-seven consecutive male patients with AS (mean age of 40.9 +/- 11.0 years) and 67 healthy controls were studied. Body composition and bone mineral density (BMD) scans were obtained using DXA. The fat free mass index (FFMI; fat-free mass divided by height squared) and the percent of fat mass (%FM) were calculated. Pre-sarcopenia was defined by low skeletal muscle mass (SMI <7.25 kg/m(2)), sarcopenia by the combined presence of the two following criteria: SMI <7.25 kg/m(2) and a low muscle strength (handgrip strength <30 kg) or a low muscle performance (timed get-up-and-go test >10 s) and cachexia by a BMI <20 kg/m(2) plus 3 from the 5 following parameters: anorexia, fatigue, handgrip strength <30 kg, CRP >5 mg/l, SMI <7.25 kg/m(2). RESULTS: Pre sarcopenia, sarcopenia, cachexia, and osteoporosis prevalences were (50.4, 34.3, 11.9, and 16.0) respectively. Patients had a mean 3 kg significant decrease in FFM and a 1 kg/m(2) decrease in appendicular mass vs. healthy controls. Pre sarcopenia, sarcopenia and cachexia were significantly associated to higher BASDAI levels and low BMD. CONCLUSION: Our study showed that men with AS had a statistically significant reduction in total and appendicular lean mass that is related to higher disease activity and significantly associated to bone loss. PMID- 27401190 TI - A toolbox to measure changes in the cell wall glycopolymer composition during differentiation of Streptomyces coelicolor A3(2). AB - Cell wall glycopolymers (CWG) represent an important component of the Gram positive cell envelope with many biological functions. The mycelial soil bacterium Streptomyces coelicolor A3(2) incorporates two distinct CWGs, polydiglycosylphosphate (PDP) and teichulosonic acid, into the cell wall of its vegetative mycelium but only little is known about their role in the complex life cycle of this microorganism. In this study we established assays to measure the total amount of CWGs in mycelial cell walls and spore walls, to quantify the individual CWGs and to determine the length of PDP. By applying these assays, we discovered that the relative amount of CWGs, especially of PDP, is reduced in spores compared to vegetative mycelium. Furthermore we found that PDP extracted from mycelial cell walls consisted of at least 19 repeating units, whereas spore walls contained substantially longer PDP polymers. PMID- 27401191 TI - Stevens Johnson syndrome/toxic epidermal necrolysis after exogenous contact to S,S-dimethyl cyanoimidodithiocarbonate. PMID- 27401193 TI - Response to 'Morbidity after laparoscopic and open rectal cancer surgery: a comparative analysis of morbidity in octogenarians and younger patients'. PMID- 27401192 TI - Diets for patients with chronic kidney disease, should we reconsider? AB - Here we revisit how dietary factors could affect the treatment of patients with complications of chronic kidney disease (CKD), bringing to the attention of the reader the most recent developments in the field. We will briefly discuss five CKD-induced complications that are substantially improved by dietary manipulation: 1) metabolic acidosis and the progression of CKD; 2) improving the diet to take advantage of the benefits of angiotensin converting enzyme inhibitors (ACEi) on slowing the progression of CKD; 3) the diet and mineral bone disorders in CKD; 4) the safety of nutritional methods utilizing dietary protein restriction; and 5) evidence that new strategies can treat the loss of lean body mass that is commonly present in patients with CKD. PMID- 27401194 TI - End-of-life care should be the same for all. PMID- 27401195 TI - Chronic oedema in the older population living in the community. PMID- 27401196 TI - Oral health of older people living in the community. PMID- 27401197 TI - Developing a postal screening tool for frailty in primary care: a secondary data analysis. AB - The purpose of this secondary data analysis (SDA) was to review a subset of quantitative and qualitative paired data sets from a returned postal screening tool (PST) completed by patients and compare them to the clinical letters composed by elderly care community nurses (ECCN) following patient assessment to ascertain the tool's reliability and validity. The aim was to understand to what extent the problems identified by patients in PSTs aligned with actual or potential problems identified by the ECCNs. The researcher examined this connection to establish whether the PST was a valid, reliable approach to proactive care. The findings of this SDA indicated that patients did understand the PST. Many appropriate referrals were made as a result of the ECCN visit that would not have occurred if the PST had not been sent. This article focuses specifically upon the physiotherapy section as this was the area where the most red flags were identified. PMID- 27401198 TI - 'No action today means no cure tomorrow': the threat of antimicrobial resistance. AB - Antimicrobial resistance is a major concern for UK healthcare professionals, following growing evidence of multi-resistant pathogens. Poor prescribing practices, partly driven by patient demand, and poor patient adherence to prescribed regimens are two of the causes of growing antimicrobial resisitance. Improved infection prevention and control practices will not only reduce healthcare-acquired infections, but also reduce the necessity for antimicrobials. Community nurses can also support their clients to promote their own health and wellbeing, increasing resilience to infections through a healthy lifestyle which includes a well-balanced diet, good personal hygiene and the take up of offered vaccinations. PMID- 27401199 TI - District nurses' experiences of musculoskeletal wellbeing: a qualitative study. AB - BACKGROUND: Musculoskeletal disorders significantly contribute to staff sickness and absence in the NHS. District nurses are especially at risk because patient handling tasks are often carried out outside a clinical environment. STUDY AIM: To explore district nurses' lived experience of musculoskeletal wellbeing. STUDY DESIGN: An exploratory qualitative study using interpretative phenomenological analysis. METHOD: Semi-structured interviews with a purposeful sample of seven district nurses. FINDINGS: Study participants accepted musculoskeletal pain as part of nursing and reported little time for physical activity, often because of work and family commitments. Participants identified treating patients' leg ulcers as a risk factor for developing MSD, while generic workplace wellbeing initiatives delivered via email failed to engage their interest. CONCLUSION: This study provides a useful insight into district nurses' experiences of musculoskeletal wellbeing and represents an important first step in producing recommendations for future research with the aim of developing strategies for improving workplace musculoskeletal wellbeing that would be acceptable to staff. PMID- 27401200 TI - NHS market liberalisation and the TTIP agreement. AB - Governments over the past three decades have undermined the founding principles of the NHS through reforms and market liberalisation. With greater involvement of commercial interests in health care, the NHS will become less democratic and transparent. Recent reforms, which were intended to improve productivity, quality and cost efficiency, have left the NHS exposed to the unwieldy model of market liberalisation and the attrition of public health care. The role of community nurses has been particularly destabilised by commissioning, as their work is difficult to measure. The advent of the Transatlantic Trade and Investment Partnership could further undermine the NHS to the benefit of international commercial interests. PMID- 27401201 TI - Nutritional pathway for people with motor neurone disease. AB - This paper provides an overview of the nutritional management and care of people living with motor neurone disease (MND) in a specialist nutrition clinic. A specialist pathway of care has been developed to enable people living with MND to undergo a percutaneous endoscopic gastrostomy (PEG) procedure in a safe way; the pathway incorporates attendance at a dedicated nutrition clinic, a stratification tool to identify patients with a high periprocedural risk and a PEG insertion team with significant experience in the MND population. Since this pathway has been in place, gastrostomies have been successfully placed in patients with a forced vital capacity (FVC) of less than 50%; previously, this would not have been possible. PMID- 27401202 TI - Supporting unpaid carers in the community. PMID- 27401203 TI - When accepting a gift can be professional misconduct and theft. AB - Gifts are often given as tokens of gratitude by grateful patients to district nurses. However, there are circumstances where the Nursing and Midwifery Council (NMC), as the professional regulator, and the courts, have held that accepting gifts, large or small, from vulnerable adults is dishonest and amounts to professional misconduct and even theft. Richard Griffith discusses the circumstances where a district nurse who accepts a gift can face a fitness-to practise investigation and an allegation of theft. PMID- 27401204 TI - For they don't know what they don't know. PMID- 27401205 TI - Supporting self-care: the principles of PAM. PMID- 27401206 TI - Development and testing of study tools and methods to examine ethnic bias and clinical decision-making among medical students in New Zealand: The Bias and Decision-Making in Medicine (BDMM) study. AB - BACKGROUND: Health provider racial/ethnic bias and its relationship to clinical decision-making is an emerging area of research focus in understanding and addressing ethnic health inequities. Examining potential racial/ethnic bias among medical students may provide important information to inform medical education and training. This paper describes the development, pretesting and piloting of study content, tools and processes for an online study of racial/ethnic bias (comparing Maori and New Zealand European) and clinical decision-making among final year medical students in New Zealand (NZ). METHODS: The study was developed, pretested and piloted using a staged process (eight stages within five phases). Phase 1 included three stages: 1) scoping and conceptual framework development; 2) literature review and identification of potential measures and items; and, 3) development and adaptation of study content. Three main components were identified to assess different aspects of racial/ethnic bias: (1) implicit racial/ethnic bias using NZ-specific Implicit Association Tests (IATs); (2) explicit racial/ethnic bias using direct questions; and, (3) clinical decision making, using chronic disease vignettes. Phase 2 (stage 4) comprised expert review and refinement. Formal pretesting (Phase 3) included construct testing using sorting and rating tasks (stage 5) and cognitive interviewing (stage 6). Phase 4 (stage 7) involved content revision and building of the web-based study, followed by pilot testing in Phase 5 (stage 8). RESULTS: Materials identified for potential inclusion performed well in construct testing among six participants. This assisted in the prioritisation and selection of measures that worked best in the New Zealand context and aligned with constructs of interest. Findings from the cognitive interviewing (nine participants) on the clarity, meaning, and acceptability of measures led to changes in the final wording of items and ordering of questions. Piloting (18 participants) confirmed the overall functionality of the web-based questionnaire, with a few minor revisions made to the final study. CONCLUSIONS: Robust processes are required in the development of study content to assess racial/ethnic bias in order to optimise the validity of specific measures, ensure acceptability and minimise potential problems. This paper has utility for other researchers in this area by informing potential development approaches and identifying possible measurement tools. PMID- 27401207 TI - Photoinduced electron transfer from quantum dots to TiO2: elucidating the involvement of excitonic and surface states. AB - Colloidal semiconductor quantum dots (QDs) exhibit excitonic and surface states, both of which may participate in charge-transfer processes relevant to solar energy conversion. To explore this inherent complexity of the charge-transfer mechanisms of QDs, we used steady-state and time-resolved emission measurements to characterize excited-state electron transfer (ET) from core-only CdSe QDs and core/shell CdSe/ZnS QDs to TiO2 nanoparticles (NPs). Core-only QDs transferred electrons from both excitonic and surface states to TiO2 with rate constants of ET (ket) of approximately (1-3) * 10(8) s(-1) and (4-7) * 10(7) s(-1), respectively. Efficiencies of ET (etaet) from excitonic and surface states were approximately 71-82% and 64-76%, respectively. Thus, trapping of electrons lowered their potential energy but did not greatly affect the efficiency of their transfer to TiO2. Photogenerated holes were transferred from core-only CdSe QDs to adsorbed 3-mercaptopropionic acid (MPA), which linked the QDs to TiO2. We characterized core/shell CdSe/ZnS QDs as alternatives to core-only QDs. The ZnS shell eliminated the undesirable trapping of electrons and transfer of photogenerated holes to MPA. We measured ket of approximately (1-3) * 10(8) s(-1) and etaet of approximately 66-85% for ET from excitonic states of core/shell CdSe/ZnS QDs to TiO2 NPs. The insensitivity of ket to the presence of the ZnS shell may have arisen from increased cross-linking of core/shell QDs to TiO2. Our results highlight the involvement of surface states in excited-state ET processes of core-only QDs and, for the heterostructures reported here, the improved performance of core/shell CdSe/ZnS QDs relative to core-only CdSe QDs. PMID- 27401209 TI - Impact of Elevated Serum Uric Acid Levels on Systemic Inflammation in Patients With Psoriasis. AB - Patients with psoriasis have increased systemic inflammation and serum uric acid (SUA) levels compared with the general population. However, the role of SUA in modulating inflammation in these patients is not known. We evaluated the associations of SUA with inflammation and psoriasis severity; 199 patients with psoriasis and 54 healthy volunteers were included in the study. Demographic features, Psoriasis Area and Severity Index (PASI) scores, and laboratory data including SUA, C-reactive protein (CRP), and neutrophil to lymphocyte ratio (NLR) were collected. Patients with psoriasis had higher fasting blood glucose, body mass index (BMI), CRP, SUA, white blood cell (WBC) count, neutrophil count, and NLR compared with controls. The PASI score positively correlated only with CRP ( r = .185, P = .012) and NLR ( r = .313, P < .001). The BMI, WBC count, PASI score, and CRP, but not SUA, appeared as independent associates of NLR in patients with psoriasis in linear regression analysis. Neutrophil to lymphocyte ratio and SUA were significantly increased in patients with psoriasis compared with controls. Neutrophil to lymphocyte ratio and CRP were independent predictors of PASI score, whereas SUA was not. Serum uric acid seemed not to modulate the inflammation seen in patients with psoriasis in our cohort. PMID- 27401208 TI - Cholest-4-en-3-one attenuates TGF-beta responsiveness by inducing TGF-beta receptors degradation in Mv1Lu cells and colorectal adenocarcinoma cells. AB - PURPOSE: The transforming growth factor-beta (TGF-beta) pathway is an important in the initiation and progression of cancer. Due to a strong association between an elevated colorectal cancer risk and increase fecal excretion of cholest-4-en-3 one, we aim to determine the effects of cholest-4-en-3-one on TGF-beta signaling in the mink lung epithelial cells (Mv1Lu) and colorectal cancer cells (HT29) in vitro. METHODS: The inhibitory effects of cholest-4-en-3-one on TGF-beta-induced Smad signaling, cell growth inhibition, and the subcellular localization of TGF beta receptors were investigated in epithelial cells using a Western blot analysis, luciferase reporter assays, DNA synthesis assay, confocal microscopy, and subcellular fractionation. RESULTS: Cholest-4-en-3-one attenuated TGF-beta signaling in Mv1Lu cells and HT29 cells, as judged by a TGF-beta-specific reporter gene assay of plasminogen activator inhibitor-1 (PAI-1), Smad2/3 phosphorylation and nuclear translocation. We also discovered that cholest-4-en-3 one suppresses TGF-beta responsiveness by increasing lipid raft and/or caveolae accumulation of TGF-beta receptors and facilitating rapid degradation of TGF-beta and thus suppressing TGF-beta-induced signaling. CONCLUSIONS: Our results suggest that cholest-4-en-3-one inhibits TGF-beta signaling may be due, in part to the translocation of TGF-beta receptor from non-lipid raft to lipid raft microdomain in plasma membranes. Our findings also implicate that cholest-4-en-3-one may be further explored for its potential role in colorectal cancer correlate to TGF beta deficiency. PMID- 27401210 TI - From Femoral to Radial Approach in Coronary Intervention. AB - Since the first cardiac catheterization in 1929, this procedure has evolved considerably. Historically performed via the transfemoral access, in the last years, the transradial access has been spreading gradually due to its many advantages. We have conducted a review of published literature concerning efficacy, safety, and cost-effectiveness, and we analyzed our patients' data, including the results of the recently published Minimizing Adverse hemorrhagic events by TRansradial access site and systemic implementation of angioX (MATRIX) study. This review confirmed the superiority of the transradial access compared to the femoral access, especially regarding complications related to the access site, duration of hospitalization, and comfort for the patient. The transradial approach is an excellent option for coronary angiography, and the procedure's risks are reduced by increased operator experience. PMID- 27401212 TI - In silico studies on potential MCF-7 inhibitors: a combination of pharmacophore and 3D-QSAR modeling, virtual screening, molecular docking, and pharmacokinetic analysis. AB - Gallic acid and its derivatives exhibit a diverse range of biological applications, including anti-cancer activity. In this work, a data-set of forty six molecules containing the galloyl moiety, and known to show anticarcinogenic activity against the MCF-7 human cancer cell line, have been chosen for pharmacophore modeling and 3D-Quantitative Structure Activity Relationship (3D QSAR) studies. A tree-based partitioning algorithm has been used to find common pharmacophore hypotheses. The QSAR model was generated for three, four, and five featured hypotheses with increasing PLS factors and analyzed. Results for five featured hypotheses with three acceptors and two aromatic rings were the best out of all the possible combinations. On analyzing the results, the most robust (R2 = .8990) hypothesis with a good predictive power (Q2 = .7049) was found to be AAARR.35. A good external validation (R2 = .6109) was also obtained. In order to design new MCF-7 inhibitors, the QSAR model was further utilized in pharmacophore based virtual screening of a large database. The predicted IC50 values of the identified potential MCF-7 inhibitors were found to lie in the micromolar range. Molecular docking into the colchicine domain of tubulin was performed in order to examine one of the probable mechanisms. This revealed various interactions between the ligand and the active site protein residues. The present study is expected to provide an effective guide for methodical development of potent MCF-7 inhibitors. PMID- 27401211 TI - Intraventricular intracranial pressure monitoring improves the outcome of older adults with severe traumatic brain injury: an observational, prospective study. AB - BACKGROUND: Intracranial pressure (ICP) monitoring is widely used in the management of patients with severe traumatic brain injury (TBI). However, there is limited evidence about the efficacy of ICP monitoring in older subjects (aged >=65 years). This study evaluated the effect of intraventricular ICP monitoring on the outcome of older adults suffering from a severe TBI. METHODS: This prospective, observational study included 166 older TBI patients (aged >=65 years) with Glasgow Coma scale (GCS) scores lower than 9 at admission. The study cohort was divided into two groups, intraventricular ICP monitoring and non-ICP monitoring. The primary outcome was in-hospital mortality. The secondary outcomes included the Glasgow Outcome Scale (GOS) score 6 months after injury, the ICU and total hospital lengths of stay, and mechanical ventilation days. RESULTS: There were 80 patients in the intraventricular ICP monitoring group and 86 patients in non-ICP monitoring group. There was no statistical difference between groups in demographics and severity of head injury. Patients treated with intraventricular ICP monitoring had lower in-hospital mortality (33.8 % vs 51.2 %, P < 0.05), a higher 6-month GOS score (3.0 +/- 1.4 vs 2.5 +/- 1.2 P < 0.05), and a lower dosage (514 +/- 246 g vs 840 +/- 323 g, P < 0.0001) and shorter duration (7.2 +/- 3.6 days vs 8.4 +/- 4.3 days, P < 0.01) of mannitol use. However, the ICU length of stay (14.3 +/- 6.4 days vs 11.6 +/- 5.8 days, P < 0.01) and mechanical ventilation days (6.7 +/- 3.5 days vs 5.6 +/- 2.4 days, P < 0.05) were longer in the ICP monitoring group. The total length of hospital stay did not differ between the two groups (28.5 +/- 12.1 days vs 26.1 +/- 13.5 days, P = 0.23). CONCLUSIONS: Intraventricular ICP monitoring may have beneficial effects on the decreased in-hospital mortality and improved 6-month outcome of older patients with severe TBI. However, given that this was an observational study conducted in a single institution, further well-designed randomized control trials are needed to evaluate the effect of intraventricular ICP monitoring on the outcome of older severe TBI patients. PMID- 27401213 TI - Assessing health impacts of the December 2013 Ice storm in Ontario, Canada. AB - BACKGROUND: Ice, or freezing rain storms have the potential to affect human health and disrupt normal functioning of a community. The purpose of this study was to assess acute health impacts of an ice storm that occurred in December 2013 in Toronto, Ontario, Canada. METHODS: Data on emergency department visits were obtained from the National Ambulatory Care Reporting System. Rates of visits in Toronto during the storm period (December 21, 2013 - January 1, 2014) were compared to rates occurring on the same dates in the previous five years (historical comparison) and compared to those in a major unaffected city, Ottawa, Ontario (geographic comparison). Overall visits and rates for three categories of interest (cardiac conditions, environmental causes and injuries) were assessed. Rate ratios were calculated using Poisson regression with population counts as an offset. Absolute counts of carbon monoxide poisoning were compared descriptively in a sub-analysis. RESULTS: During the 2013 storm period, there were 34 549 visits to EDs in Toronto (12.46 per 1000 population) compared with 10 794 visits in Ottawa (11.55 per 1000 population). When considering year and geography separately, rates of several types of ED visits were higher in the storm year than in previous years in both Toronto and Ottawa. Considering year and geography together, rates in the storm year were higher for overall ED visits (RR: 1.10, 95 % CI: 1.09-1.11) and for visits due to environmental causes (RR: 2.52, 95 % CI: 2.21-2.87) compared to previous years regardless of city. For injuries, visit rates were higher in the storm year in both Toronto and Ottawa, but the increase in Toronto was significantly greater than the increase in Ottawa, indicating a significant interaction between geography and year (RR: 1.23, 95 % CI: 1.16 1.30). CONCLUSIONS: This suggests that the main health impact of the 2013 Ice Storm was an increase in ED visits for injuries, while other increases could have been due to severe weather across Ontario at that time. This study is one of the first to use a population-level database and regression modeling of emergency visit codes to identify acute impacts resulting from ice storms. PMID- 27401216 TI - Pretracheal tumor-shaped inflammatory plaque revealing underlying thyroid malignancy. PMID- 27401215 TI - Mechanism of Self-Regulation and In Vivo Performance of the Cleveland Clinic Continuous-Flow Total Artificial Heart. AB - Cleveland Clinic's continuous-flow total artificial heart (CFTAH) provides systemic and pulmonary circulations using one assembly (one motor, two impellers). The right pump hydraulic output to the pulmonary circulation is self regulated by the rotating assembly's passive axial movement in response to atrial differential pressure to balance itself to the left pump output. This combination of features integrates a biocompatible, pressure-balancing regulator with a double-ended pump. The CFTAH requires no flow or pressure sensors. The only control parameter is pump speed, modulated at programmable rates (60-120 beats/min) and amplitudes (0 to +/-25%) to provide flow pulses. In bench studies, passive self-regulation (range: -5 mm Hg <= [left atrial pressure - right atrial pressure] <= 10 mm Hg) was demonstrated over a systemic/vascular resistance ratio range of 2.0-20 and a flow range of 3-9 L/min. Performance of the most recent pump configuration was demonstrated in chronic studies, including three consecutive long-term experiments (30, 90, and 90 days). These experiments were performed at a constant postoperative mean speed with a +/-15% speed modulation, demonstrating a totally self-regulating mode of operation, from 3 days after implant to explant, despite a weight gain of up to 40%. The mechanism of self regulation functioned properly, continuously throughout the chronic in vivo experiments, demonstrating the performance goals. PMID- 27401217 TI - Lingual nerve injury in association with sagittal ramus osteotomy and bicortical screw fixation: a review of 523 procedures in 262 subjects. AB - The purpose of this study was to assess the frequency of irreversible lingual nerve (LN) injury in patients undergoing sagittal ramus osteotomies (SRO) with bicortical screw fixation. A retrospective cohort study of patients treated by a single surgeon was performed (follow-up 2-11 years). The sample consisted of a series of subjects with a bimaxillary dentofacial deformity (DFD). The SRO and bicortical screw fixation techniques were consistent. The primary outcome variable was the prevalence of irreversible LN injury. Two hundred sixty-two subjects undergoing 523 SROs with bicortical screw fixation met the inclusion criteria. Average age at operation was 25 years (range 13-63 years) and there were 134 females (51%). The majority of SROs were fixated with three bicortical screws (92%). Simultaneous third molar removal was done in 209 of the 523 SROs (40%). For primary mandibular deficiency subjects (n=40), the mean mandibular advancement was 11.0mm (range 5-17mm), with 42.5% undergoing counter-clockwise rotation. In the study group (n=523 SRO's) there was one irreversible LN injury (<1%). This study confirmed a lack of association of LN injury at the time of SRO with sex, age at operation, simultaneous removal of a third molar, use of bicortical screw fixation, pattern of DFD, and extent of mandibular advancement. PMID- 27401214 TI - Clinician Perspectives on Current Issues in Lung Cancer Drug Development. AB - Recent advances in molecularly targeted therapy and immunotherapy offer a glimmer of hope for potentially realizing the dream of personalized therapy for lung cancer. This article highlights current questions in clinical trial design, enrollment strategies and patient focused drug development, with particular emphasis on unique issues in trials of targeted therapy and immunotherapy. PMID- 27401219 TI - Transcriptome meta-analysis of three follicular compartments and its correlation with ovarian follicle maturity and oocyte developmental competence in cows. AB - Oocyte developmental competence in superstimulated cows is dependent in part on the duration of the FSH coasting. FSH coasting refers to superstimulation with FSH (2 days of endogenous FSH following follicle ablation and 3 days of FSH injections) followed by no FSH for a specific duration. The optimal duration varies among individuals. FSH coasting appears to modulate the transcriptome of different follicular compartments, which cooperate as a single functional unit. However, the integrative effects of FSH coasting on different follicular compartments remain ambiguous. Meta-analysis of three independent transcriptome studies, each focused on a single cell type (granulosa, cumulus, and oocyte) during FSH coasting, allowed the identification of 12 gene clusters with similar time-course expression patterns in all three compartments. Network analysis identified HNF4A (involved in metabolic functions) and ELAVL1 (an RNA-binding protein) as hub genes regulated respectively upward and downward in the clusters enriched at the optimal coasting time, and APP (involved in mitochondrial functions) and COPS5 (a member of the COP9 signalosome) as hub genes regulated respectively upwards and downwards in the clusters enriched progressively throughout the coasting period. We confirmed the effects on HNF4A downstream targets (TTR, PPL) and other hub genes (ELAVL1, APP, MYC, and PGR) in 30 cows with RT-quantitative PCR. The correlation of hub gene expression levels with FSH coasting indicated that a combination of these genes could predict oocyte competence with 83% sensitivity, suggesting that they are potential biomarkers of follicle differentiation. These findings could be used to optimize FSH coasting on an individual basis. PMID- 27401221 TI - CardioPulse Articles. PMID- 27401220 TI - Controversies in interventional cardiology: eminence, common sense, and evidence. PMID- 27401218 TI - Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue. AB - The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health. PMID- 27401224 TI - Prognostic factors for survival in patients with amyotrophic lateral sclerosis: analysis of a multi-centre clinical trial. AB - Information regarding factors influencing prognosis and quality of life (QoL) in patients with amyotrophic lateral sclerosis (ALS) is useful for clinicians and also for patients and their carers. The aims of this study are to identify prognostic factors for survival in ALS and to determine the physical factors influencing QoL. This study is a retrospective analysis of a cohort of 512 patients who participated in a phase II/III clinical trial of olesoxime. Cox multivariate regression analysis found older age, bulbar onset disease, low baseline forced vital capacity, low baseline manual muscle test (MMT) scores and a shorter diagnostic delay to be independently associated with poor survival outcome. Physical factors shown to have the strongest correlation with poor QoL were low weight and a reduced ability to climb stairs. Therapeutic interventions including gastrostomy and non-invasive ventilation had no positive impact on QoL in this cohort. The prognostic factors for survival identified here are consistent with other studies of ALS patients, with the additional identification of baseline MMT score as another predictor of prognosis. Furthermore, the correlation between both weight and poor lower limb function with QoL is novel and underlines the importance of careful nutritional management in this hypercatabolic condition. PMID- 27401222 TI - Lithium-responsive genes and gene networks in bipolar disorder patient-derived lymphoblastoid cell lines. AB - Lithium (Li) is the mainstay mood stabilizer for the treatment of bipolar disorder (BD), although its mode of action is not yet fully understood nor is it effective in every patient. We sought to elucidate the mechanism of action of Li and to identify surrogate outcome markers that can be used to better understand its therapeutic effects in BD patients classified as good (responders) and poor responders (nonresponders) to Li treatment. To accomplish these goals, RNA sequencing gene expression profiles of lymphoblastoid cell lines (LCLs) were compared between BD Li responders and nonresponders with healthy controls before and after treatment. Several Li-responsive gene coexpression networks were discovered indicating widespread effects of Li on diverse cellular signaling systems including apoptosis and defense response pathways, protein processing and response to endoplasmic reticulum stress. Individual gene markers were also identified, differing in response to Li between BD responders and nonresponders, involved in processes of cell cycle and nucleotide excision repair that may explain part of the heterogeneity in clinical response to treatment. Results further indicated a Li gene expression signature similar to that observed with clonidine treatment, an alpha2-adrenoceptor agonist. These findings provide a detailed mechanism of Li in LCLs and highlight putative surrogate outcome markers that may permit for advanced treatment decisions to be made and for facilitating recovery in BD patients. PMID- 27401225 TI - Thirty-day readmission rate and risk factors for patients undergoing single level elective anterior lumbar interbody fusion (ALIF). AB - Anterior lumbar interbody fusion (ALIF) represents a common interbody fusion technique and is advantageous given reduced risk of damage to the paraspinal muscles, posterior ligaments, and neural elements. In this study, we identified the readmission rate, common causes, and risk factors associated with single level ALIF 30-day readmission. Patients who underwent elective single level ALIF surgery from 2011 to 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Segmental fusion, emergency, and trauma cases were excluded. A total of 2,042 patients were identified from the ACS-NSQIP database from 2011 to 2013. The proportion of patients readmitted was 5.19% (106/2,042) and approximately 59.81% (64/106) had a reportable cause. The top three causes were poor post-operative pain control (11%), deep (9%) and superficial (9%) surgical site infections. Risk factors associated with 30-day readmission included age (odds ratio (OR)=1.02, 95% confidence interval (CI): 1.00-1.03, p value=0.05), history of severe chronic obstructive pulmonary disease (COPD), (OR=2.11, 95% CI: 0.95-4.70, p value=0.08), post-operative pneumonia (OR=6.58, 95% CI: 2.36-18.30, p value<0.001), and presence of superficial surgical site infection (OR=11.68, 95% CI: 4.88-27.95, p value<0.001). Bleeding disorders, anemia, and perioperative blood loss was not associated with 30-day readmission. Limitations include retrospective level 3 data, and missing data. This study represents the first nation-wide descriptive evaluation of 30-day readmission causes and risk factors for patients undergoing an ALIF procedure. PMID- 27401226 TI - Effects of chronic alcohol consumption on long-term outcomes of thalamic deep brain stimulation for essential tremor. AB - The prevalence of essential tremor (ET) is about 4% above 40years of age. Chronic alcohol consumption is present in around 20% of patients with ET. Our objective was to identify whether chronic alcohol consumption was associated with a negative effect on tremor outcome after thalamic deep brain stimulation (DBS) in ET patients. We conducted a retrospective chart review, from January 2005 to December 2012, from which 23 patients who had ventral intermediate nucleus (Vim) DBS surgery for ET were identified. Seven patients had a positive history of chronic alcohol consumption. We defined as chronic alcohol users those patients with a habit of drinking alcohol every day in order to suppress tremor. In the overall group of 23 patients, there was a reduction in the median tremor score from 8 pre-operatively, to 1 post-operatively (p<0.0001). The alcohol consumers group experienced a reduction in the median tremor score from 6 pre-operatively to 0 post-operatively (p=0.03). The non-alcohol consumers group had a reduction in the median tremor score from 8 pre-operatively to 1.7 post-operatively (p<0.0001). Both groups of patients experienced significant benefit from thalamic DBS. A larger study may reveal statistically significant differences between subgroups. PMID- 27401223 TI - Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review. AB - Mendelian diseases contain important biological information regarding developmental effects of gene mutations that can guide drug discovery and toxicity efforts. In this review, we focus on Smith-Lemli-Opitz syndrome (SLOS), a rare Mendelian disease characterized by compound heterozygous mutations in 7 dehydrocholesterol reductase (DHCR7) resulting in severe fetal deformities. We present a compilation of SLOS-inducing DHCR7 mutations and the geographic distribution of those mutations in healthy and diseased populations. We observed that several mutations thought to be disease causing occur in healthy populations, indicating an incomplete understanding of the condition and highlighting new research opportunities. We describe the functional environment around DHCR7, including pharmacological DHCR7 inhibitors and cholesterol and vitamin D synthesis. Using PubMed, we investigated the fetal outcomes following prenatal exposure to DHCR7 modulators. First-trimester exposure to DHCR7 inhibitors resulted in outcomes similar to those of known teratogens (50 vs 48% born-healthy). DHCR7 activity should be considered during drug development and prenatal toxicity assessment. PMID- 27401227 TI - Susceptibility to cephalosporins of bacteria causing intramammary infections in dairy cows with a high somatic cell count in Germany. AB - The objective of this cross-sectional study was to determine the minimal inhibitory concentrations of cephalosporins of the first (cefalonium and cefapirin) and fourth generation (cefquinome) against bacteria isolated from intramammary infections in dairy cows with elevated somatic cell counts in Germany. Additionally, possible regional differences of the minimal inhibitory concentrations within Germany should be evaluated. In total, 6936 quarter milk samples from cows with a somatic cell count >200,000cells/ml were taken in 43 herds. The concentrations of the first generation cephalosporins inhibiting at least 90% of the isolates of a pathogen (MIC90) were >=64MUg/ml against Gram negative bacteria and enterococci whereas the respective MIC90 against the other Gram-positive bacteria were <=4MUg/ml. The MIC90 of cefquinome were >=16MUg/ml against Gram-negative bacteria, bacilli and enterococci, and <=2MUg/ml against the other Gram-positive bacteria. Only the minimal inhibitory concentrations against coagulase-negative staphylococci differed significantly between regions in parametric survival models with shared frailties for the herds. However, the minimal inhibitory concentrations of cefquinome against staphylococci were higher than the minimal inhibitory concentrations of the tested cephalosporins of the first generation. Therefore, cefquinome should not be the first choice to treat staphylococcal mastitis in dairy cows. PMID- 27401229 TI - Genomic Response to Selection for Predatory Behavior in a Mammalian Model of Adaptive Radiation. AB - If genetic architectures of various quantitative traits are similar, as studies on model organisms suggest, comparable selection pressures should produce similar molecular patterns for various traits. To test this prediction, we used a laboratory model of vertebrate adaptive radiation to investigate the genetic basis of the response to selection for predatory behavior and compare it with evolution of aerobic capacity reported in an earlier work. After 13 generations of selection, the proportion of bank voles (Myodes [=Clethrionomys] glareolus) showing predatory behavior was five times higher in selected lines than in controls. We analyzed the hippocampus and liver transcriptomes and found repeatable changes in allele frequencies and gene expression. Genes with the largest differences between predatory and control lines are associated with hunger, aggression, biological rhythms, and functioning of the nervous system. Evolution of predatory behavior could be meaningfully compared with evolution of high aerobic capacity, because the experiments and analyses were performed in the same methodological framework. The number of genes that changed expression was much smaller in predatory lines, and allele frequencies changed repeatably in predatory but not in aerobic lines. This suggests that more variants of smaller effects underlie variation in aerobic performance, whereas fewer variants of larger effects underlie variation in predatory behavior. Our results thus contradict the view that comparable selection pressures for different quantitative traits produce similar molecular patterns. Therefore, to gain knowledge about molecular-level response to selection for complex traits, we need to investigate not only multiple replicate populations but also multiple quantitative traits. PMID- 27401228 TI - Viscoelasticity of subcortical gray matter structures. AB - Viscoelastic mechanical properties of the brain assessed with magnetic resonance elastography (MRE) are sensitive measures of microstructural tissue health in neurodegenerative conditions. Recent efforts have targeted measurements localized to specific neuroanatomical regions differentially affected in disease. In this work, we present a method for measuring the viscoelasticity in subcortical gray matter (SGM) structures, including the amygdala, hippocampus, caudate, putamen, pallidum, and thalamus. The method is based on incorporating high spatial resolution MRE imaging (1.6 mm isotropic voxels) with a mechanical inversion scheme designed to improve local measures in pre-defined regions (soft prior regularization [SPR]). We find that in 21 healthy, young volunteers SGM structures differ from each other in viscoelasticity, quantified as the shear stiffness and damping ratio, but also differ from the global viscoelasticity of the cerebrum. Through repeated examinations on a single volunteer, we estimate the uncertainty to be between 3 and 7% for each SGM measure. Furthermore, we demonstrate that the use of specific methodological considerations-higher spatial resolution and SPR-both decrease uncertainty and increase sensitivity of the SGM measures. The proposed method allows for reliable MRE measures of SGM viscoelasticity for future studies of neurodegenerative conditions. Hum Brain Mapp 37:4221-4233, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27401230 TI - Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome. AB - Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ~0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. PMID- 27401231 TI - lolal Is an Evolutionarily New Epigenetic Regulator of dpp Transcription during Dorsal-Ventral Axis Formation. AB - Secreted ligands in the Dpp/BMP family drive dorsal-ventral (D/V) axis formation in all Bilaterian species. However, maternal factors regulating Dpp/BMP transcription in this process are largely unknown. We identified the BTB domain protein longitudinals lacking-like (lolal) as a modifier of decapentaplegic (dpp) mutations. We show that Lolal is evolutionarily related to the Trithorax group of chromatin regulators and that lolal interacts genetically with the epigenetic factor Trithorax-like during Dpp D/V signaling. Maternally driven Lolal(HA) is found in oocytes and translocates to zygotic nuclei prior to the point at which dpp transcription begins. lolal maternal and zygotic mutant embryos display significant reductions in dpp, pMad, and zerknullt expression, but they are never absent. The data suggest that lolal is required to maintain dpp transcription during D/V patterning. Phylogenetic data revealed that lolal is an evolutionarily new gene present only in insects and crustaceans. We conclude that Lolal is the first maternal protein identified with a role in dpp D/V transcriptional maintenance, that Lolal and the epigenetic protein Trithorax-like are essential for Dpp D/V signaling and that the architecture of the Dpp D/V pathway evolved in the arthropod lineage after the separation from vertebrates via the incorporation of new genes such as lolal. PMID- 27401232 TI - No Evidence That Nitrogen Limitation Influences the Elemental Composition of Isopod Transcriptomes and Proteomes. AB - The field of stoichiogenomics aims at understanding the influence of nutrient limitations on the elemental composition of the genome, transcriptome, and proteome. The 20 amino acids and the 4 nt differ in the number of nutrients they contain, such as nitrogen (N). Thus, N limitation shall theoretically select for changes in the composition of proteins or RNAs through preferential use of N-poor amino acids or nucleotides, which will decrease the N-budget of an organism. While these N-saving mechanisms have been evidenced in microorganisms, they remain controversial in multicellular eukaryotes. In this study, we used 13 surface and subterranean isopod species pairs that face strongly contrasted N limitations, either in terms of quantity or quality. We combined in situ nutrient quantification and transcriptome sequencing to test if N limitation selected for N-savings through changes in the expression and composition of the transcriptome and proteome. No evidence of N-savings was found in the total N-budget of transcriptomes or proteomes or in the average protein N-cost. Nevertheless, subterranean species evolving in N-depleted habitats displayed lower N-usage at their third codon positions. To test if this convergent compositional change was driven by natural selection, we developed a method to detect the strand asymmetric signature that stoichiogenomic selection should leave in the substitution pattern. No such signature was evidenced, indicating that the observed stoichiogenomic-like patterns were attributable to nonadaptive processes. The absence of stoichiogenomic signal despite strong N limitation within a powerful phylogenetic framework casts doubt on the existence of stoichiogenomic mechanisms in metazoans. PMID- 27401234 TI - Design and synthesis of 4'-((5-benzylidene-2,4-dioxothiazolidin-3 yl)methyl)biphenyl-2-carbonitrile analogs as bacterial peptide deformylase inhibitors. AB - Herein, we report the synthesis and screening of 4'-((5-benzylidene-2,4 dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a-j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50 value = 139.28 MUm), 11g (IC50 value = 136.18 MUm), and 11h (IC50 value = 131.65 MUm) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36-167.26 MUg/mL), 11g (MIC range = 93.75-145.67 MUg/mL), and 11h (MIC range = 63.61-126.63 MUg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00-250.00 MUg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a-j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs. PMID- 27401233 TI - Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments. AB - Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8-9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ~5* for 75 samples and ~42* for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (<100 m), high-altitude region (>1500 m) versus low-altitude region (<1300 m), desert (<10 mm average annual precipitation) versus highly humid region (>600 mm), and arid zone (<400 mm) versus humid zone (>400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change. PMID- 27401235 TI - A method for MREIT-based source imaging: simulation studies. AB - This paper aims to provide a method for using magnetic resonance electrical impedance tomography (MREIT) to visualize local conductivity changes associated with evoked neuronal activities in the brain. MREIT is an MRI-based technique for conductivity mapping by probing the magnetic flux density induced by an externally injected current through surface electrodes. Since local conductivity changes resulting from evoked neural activities are very small (less than a few %), a major challenge is to acquire exogenous magnetic flux density data exceeding a certain noise level. Noting that the signal-to-noise ratio is proportional to the square root of the number of averages, it is important to reduce the data acquisition time to get more averages within a given total data collection time. The proposed method uses a sub-sampled k-space data set in the phase-encoding direction to significantly reduce the data acquisition time. Since the sub-sampled data violates the Nyquist criteria, we only get a nonlinearly wrapped version of the exogenous magnetic flux density data, which is insufficient for conductivity imaging. Taking advantage of the sparseness of the conductivity change, the proposed method detects local conductivity changes by estimating the time-change of the Laplacian of the nonlinearly wrapped data. PMID- 27401237 TI - Driving With ADHD: Performance Effects and Environment Demand in Traffic. AB - OBJECTIVE: This research investigated the on-road driving performance of individuals with ADHD across a range of road and traffic conditions to determine whether errors were linked to situational complexity and attentional demands. METHOD: The everyday driving performance of medicated drivers with ADHD, unmedicated drivers with ADHD, and controls was tested in urban, residential, rural, and highway environments using driver license testing procedures. RESULTS: Unmedicated drivers with ADHD displayed fewer safe driving skills and committed more inattentive and impatient driving errors, particularly in low demand highway and rural driving conditions. Medicated drivers' performance was not reliably different than controls. Participants in both ADHD groups were more likely than controls to report risky driving and involvement in crashes. CONCLUSION: The results demonstrate that situations with low attentional demand are particularly risky for unmedicated ADHD drivers and suggest that focus on these situations may be useful in improving driving outcomes for this population. PMID- 27401236 TI - Relationship of surface damage appearance and volumetric wear in retrieved TKR polyethylene liners. AB - Recently developed techniques have enabled volume loss measurements on surgically retrieved total knee replacements (TKR). However, it is not well understood how volume loss relates to polyethylene surface damage appearance. Sixty-four fixed bearing cruciate retaining components retrieved from revision and postmortem surgeries were analyzed for penetration and volume loss on the topside articular surface. An autonomous reconstruction method was used to approximate the original unworn surfaces. Surface damage patterns were also mapped using a video microscope, and each pattern's contribution to volume loss was calculated. With consideration for creep, a total wear rate of 12.9 +/- 5.97 mm3 /year was found for the population. The penetration rate was 0.035 +/- 0.017 mm/year medially and 0.034 +/- 0.011 mm/year laterally, of which the location on the plateau varied greatly. Although striated patterns contributed to most to volume loss, damage patterns generally were only moderate predictors of material volume loss. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2053 2059, 2017. PMID- 27401238 TI - Child Maltreatment and Associated Parental Factors Among Children With ADHD: A Comparative Study. AB - OBJECTIVE: This study investigated the role of child and parental factors in maltreatment of children with ADHD compared with a healthy control group. METHOD: We examined the rates and correlations of child maltreatment by parents in a sample of children with ADHD ( n = 100) and a matched comparison sample of children without ADHD ( n = 100), all aged 6 to 11 years. Parent and child ratings evaluated demographic characteristics, severity of ADHD symptoms, and childhood trauma exposure. RESULTS: According to regression analysis, maternal hyperactivity/impulsivity and male gender of the child increase the emotional abuse; whereas maternal history of emotional abuse and physical neglect and paternal attention deficit increase sexual abuse, and higher maternal hyperactivity/impulsivity increases emotional neglect of ADHD children. CONCLUSION: The study's findings provide strong evidence that the maltreatment of children with ADHD is more associated with parental factors than with the symptoms of ADHD in children. PMID- 27401239 TI - Availability of Striatal Dopamine Transporter in Healthy Individuals With and Without a Family History of ADHD. AB - OBJECTIVE: ADHD is the most prevalent neurodevelopmental disorder. It is highly heritable and multifactorial, but the definitive causes remain unknown. Abnormal dopamine transporter (DAT) availability has been reported, but the data are inconsistent. The aim of this study was to examine whether DAT availability differs between healthy parents with and without ADHD offspring. METHOD: Eleven healthy parents with ADHD offspring and 11 age- and sex-matched healthy controls without ADHD offspring were recruited. The availability of DAT was approximated using single-photon emission computed tomography, with [99mTc] TRODAT-1 as the ligand. RESULTS: DAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the parents with ADHD offspring than in the healthy controls without ADHD offspring. CONCLUSION: The results suggest that ADHD could be heritable via abnormal DAT activities. PMID- 27401240 TI - Unseen and Stressed? Gender Differences in Parent and Teacher Ratings of ADHD Symptoms and Associations With Perceived Stress in Children With ADHD. AB - OBJECTIVE: In this study, we investigate the differences between parent and teacher ADHD ratings, and how these ratings relate to perceived stress in children with ADHD. METHOD: Ratings by parents and teachers with the Swanson, Nolan and Pelham ADHD symptom rating scale (SNAP-IV) were collected from children with a clinical diagnosis of ADHD (n = 137). Also, information on medication was collected. Children (>=11 years of age; n = 64) were invited to complete the Pressure-Activation-Stress scale. RESULTS: Among girls, but not boys, teacher ratings were significantly lower than parental ratings on all symptom scales. Lower teacher ratings on hyperactivity symptoms were associated with higher levels of perceived stress. CONCLUSION: The findings suggest a potential gender bias in ratings among teachers. Underrated, and hence underidentified, ADHD problems in the school setting seem to increase the perception of stress in the sense of pressure for both girls and boys. PMID- 27401241 TI - A Randomized Effectiveness Trial of a Behavioral Teacher Program Targeting ADHD Symptoms. AB - OBJECTIVE: This study investigated the effectiveness of the Positivity & Rules Program (PR program), a behavioral teacher program targeting ADHD symptoms in the classroom involving both student-focused and classroom-focused programs. METHOD: Primary school children with ADHD symptoms (N = 114) were randomly assigned to the PR program (n = 58) or control group (n = 56). Teacher and parent ratings were used to assess behavioral, social, and emotional functioning at baseline, during and after the intervention. Intervention effects were assessed using intention-to-treat multilevel analyses. RESULTS: Teachers reported positive effects on ADHD symptoms and social skills (.01 < f2 > .36). Effects did not generalize to the home setting. CONCLUSION: The PR program holds promise for improving classroom behavior in children with ADHD symptoms and might prevent escalation of problem behavior. PMID- 27401242 TI - Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers. AB - BACKGROUND: The identification of molecular mechanisms conferring resistance to tyrosine kinase inhibitor (TKI) is a key step to improve therapeutic results for patients with oncogene addiction. Several alterations leading to EGFR and anaplastic lymphoma kinase (ALK) resistance to TKI therapy have been described in non-small cell lung cancer (NSCLC). Only two mutations in the ROS1 kinase domain responsible for crizotinib resistance have been described in patients thus far. METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR) ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib. Molecular analysis (whole-exome sequencing, CGH) and functional studies were undertaken to elucidate the mechanism of resistance. Based on this case, we took advantage of the structural homology of ROS1 and ALK to build a predictive model for drug sensitivity regarding future ROS1 mutations. RESULTS: Sequencing revealed a dual mutation, S1986Y and S1986F, in the ROS1 kinase domain. Functional in vitro studies demonstrated that ROS1 harboring either the S1986Y or the S1986F mutation, while conferring resistance to crizotinib and ceritinib, was inhibited by lorlatinib (PF-06463922). The patient's clinical response confirmed the potency of lorlatinib against S1986Y/F mutations. The ROS1 S1986Y/F and ALK C1156Y mutations are homologous and displayed similar sensitivity patterns to ALK/ROS1 TKIs. We extended this analogy to build a model predicting TKI efficacy against potential ROS1 mutations. CONCLUSIONS: Clinical evidence, in vitro validation, and homology-based prediction provide guidance for treatment decision making for patients with ROS1-rearranged NSCLC who progressed on crizotinib. Clin Cancer Res; 22(24); 5983-91. (c)2016 AACR. PMID- 27401243 TI - Integrated Analysis of Multiple Biomarkers from Circulating Tumor Cells Enabled by Exclusion-Based Analyte Isolation. AB - PURPOSE: There is a critical clinical need for new predictive and pharmacodynamic biomarkers that evaluate pathway activity in patients treated with targeted therapies. A microscale platform known as VERSA (versatile exclusion-based rare sample analysis) was developed to integrate readouts across protein, mRNA, and DNA in circulating tumor cells (CTC) for a comprehensive analysis of the androgen receptor (AR) signaling pathway. EXPERIMENTAL DESIGN: Utilizing exclusion-based sample preparation principles, a handheld chip was developed to perform CTC capture, enumeration, quantification, and subcellular localization of proteins and extraction of mRNA and DNA. This technology was validated across integrated endpoints in cell lines and a cohort of patients with castrate-resistant prostate cancer (CRPC) treated with AR-targeted therapies and chemotherapies. RESULTS: The VERSA was validated in cell lines to analyze AR protein expression, nuclear localization, and gene expression targets. When applied to a cohort of patients, radiographic progression was predicted by the presence of multiple AR splice variants and activity in the canonical AR signaling pathway. AR protein expression and nuclear localization identified phenotypic heterogeneity. Next generation sequencing with the FoundationOne panel detected copy number changes and point mutations. Longitudinal analysis of CTCs identified acquisition of multiple AR variants during targeted treatments and chemotherapy. CONCLUSIONS: Complex mechanisms of resistance to AR-targeted therapies, across RNA, DNA, and protein endpoints, exist in patients with CRPC and can be quantified in CTCs. Interrogation of the AR signaling pathway revealed distinct patterns relevant to tumor progression and can serve as pharmacodynamic biomarkers for targeted therapies. Clin Cancer Res; 1-11. (c)2016 AACR. PMID- 27401244 TI - BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer. AB - PURPOSE: Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity and a tolerable safety profile. This randomized, open label, phase II trial of tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 in patients with previously untreated metastatic colorectal cancer (mCRC) evaluated tivozanib activity versus bevacizumab. EXPERIMENTAL DESIGN: Treatment-naive patients received mFOLFOX6 every 2 weeks of each 28-day cycle plus either tivozanib orally 1.5 mg once daily for 21 days or bevacizumab intravenously 5 mg/kg every 2 weeks. Investigator-assessed progression-free survival (PFS) was the primary endpoint; some secondary endpoints included safety, overall survival, overall response rate (ORR), duration of response, time to treatment failure, and biomarker subgroup analyses. RESULTS: A prespecified interim futility analysis demonstrated that the futility boundary for superiority of tivozanib/mFOLFOX6 over bevacizumab/mFOLFOX6 for PFS in the intent-to-treat population was crossed; median PFS was 9.4 versus 10.7 months [HR = 1.091; confidence interval (CI), 0.693-1.718; P = 0.706]. Tivozanib/mFOLFOX6 resulted in PFS and ORR comparable with bevacizumab/mFOLFOX6; interim analyses biomarker results revealed no significant PFS association. Post hoc final analyses demonstrated a potential difference in tivozanib-specific PFS in patients with low neuropilin-1 (NRP-1), but not in patients with high NRP-1. Tivozanib/mFOLFOX6 was tolerable and adverse events were comparable with both bevacizumab/mFOLFOX6 and previous tivozanib studies. CONCLUSIONS: The efficacy of tivozanib/mFOLFOX6 was comparable with but not superior to bevacizumab/mFOLFOX6 in patients with previously untreated mCRC. Since data from the prespecified interim analysis did not demonstrate superiority, this resulted in discontinuation of the study. The safety and tolerability profile of tivozanib/mFOLFOX6 was consistent with other tivozanib trials. NRP-1 is a potential predictive biomarker for tivozanib activity, but these results require further validation. Clin Cancer Res; 22(20); 5058-67. (c)2016 AACR. PMID- 27401245 TI - c-Myc Alteration Determines the Therapeutic Response to FGFR Inhibitors. AB - Purpose: Lately, emerging evidence has suggested that oncogenic kinases are associated with specific downstream effectors to govern tumor growth, suggesting potential translational values in kinase-targeted cancer therapy. Tyrosine kinase FGFR, which is aberrant in various cancer types, is one of the most investigated kinases in molecularly targeted cancer therapy. Herein, we investigated whether there exists key downstream effector(s) that converges FGFR signaling and determines the therapeutic response of FGFR-targeted therapy.Experimental Design: A range of assays was used to assess the role of c-Myc in FGFR aberrant cancers and its translational relevance in FGFR-targeted therapy, including assessment of drug sensitivity using cell viability assay, signaling transduction profiling using immunoblotting, and in vivo antitumor efficacy using cancer cell line-based xenografts and patient-derived xenografts models.Results: We discovered that c Myc functioned as the key downstream effector that preceded FGFR-MEK/ERK signaling in FGFR aberrant cancer. Disruption of c-Myc overrode the cell proliferation driven by constitutively active FGFR. FGFR inhibition in FGFR addicted cancer facilitated c-Myc degradation via phosphorylating c-Myc at threonine 58. Ectopic expression of undegradable c-Myc mutant conferred resistance to FGFR inhibition both in vitro and in vivo c-Myc level alteration stringently determined the response to FGFR inhibitors, as demonstrated in FGFR responsive cancer subset, as well as cancers bearing acquired or de novo resistance to FGFR inhibition.Conclusions: This study reveals a stringent association between FGFR and the downstream effector c-Myc in FGFR-dependent cancers, and suggests the potential therapeutic value of c-Myc in FGFR-targeted cancer therapy. Clin Cancer Res; 23(4); 974-84. (c)2016 AACR. PMID- 27401246 TI - Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual. AB - Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. (c)2016 AACRSee related commentary by Mileham and Kim, p. 5397. PMID- 27401247 TI - FDA Approval: Uridine Triacetate for the Treatment of Patients Following Fluorouracil or Capecitabine Overdose or Exhibiting Early-Onset Severe Toxicities Following Administration of These Drugs. AB - On December 11, 2015, the FDA approved uridine triacetate (VISTOGARD; Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, and of those who exhibit early-onset, severe, or life threatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Uridine triacetate is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs, and the safety and efficacy of uridine triacetate initiated more than 96 hours following the end of administration of these drugs has not been established. The approval is based on data from two single-arm, open-label, expanded-access trials in 135 patients receiving uridine triacetate (10 g or 6.2 g/m(2) orally every 6 hours for 20 doses) for fluorouracil or capecitabine overdose, or who exhibited severe or life threatening toxicities within 96 hours following the end of fluorouracil or capecitabine administration. Ninety-six percent of patients met the major efficacy outcome measure, which was survival at 30 days or survival until the resumption of chemotherapy, if prior to 30 days. The most common adverse reactions were vomiting, nausea, and diarrhea. This article summarizes the FDA review of this New Drug Application, the data supporting approval of uridine triacetate, and the unique regulatory situations encountered by this approval. Clin Cancer Res; 22(18); 4545-49. (c)2016 AACR. PMID- 27401249 TI - Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor Cells. AB - PURPOSE: High VEGF expression in ovarian cancer is an unfavorable prognostic factor. However, the role of VEGF in tumor immunity remains unclear. Here, we examined the impact of VEGF on local immunity, including induction of myeloid derived suppressor cells (MDSC), in ovarian cancer. EXPERIMENTAL DESIGN: High grade serous ovarian cancer (HGSOC) cases were analyzed by gene expression microarray and IHC for VEGF, CD8, and CD33. VEGF receptor (VEGFR) 1 and VEGFR2 expression levels on MDSCs were analyzed in a mouse model, and the direct effects of VEGF-A on MDSC expansion were investigated. Gr1+ MDSCs and lymphocyte frequencies were analyzed in control tumors and tumors derived from cells harboring short hairpin RNA targeting Vegf-a. In addition, the therapeutic effects of anti-Gr-1 antibodies were examined. RESULTS: Microarray analysis revealed the upregulation of several myeloid cell chemoattractants and the downregulation of lymphocyte-related pathways in cases with high VEGF expression. In immunohistochemical analysis, VEGF expression in peritoneal dissemination correlated with MDSC infiltration. Cases with high MDSC infiltration, which was inversely correlated with intratumoral CD8+ T-cell infiltration, exhibited shorter overall survival. In a mouse model, intratumoral MDSCs expressed both VEGFR1 and VEGFR2. MDSC migration and differentiation were augmented by VEGF signaling. Vegf-a knockdown in tumor cells resulted in decreased MDSC infiltration and increased CD8+ T-cell infiltration. Moreover, treatment with anti-Gr-1 antibodies delayed the growth of control tumors, whereas Vegf-a knockdown tumors were unaffected by anti-Gr-1 antibody treatment. CONCLUSIONS: VEGF expression in ovarian cancer induced MDSCs, inhibited local immunity, and contributed to poor prognosis. Clin Cancer Res; 23(2); 587-99. (c)2016 AACR. PMID- 27401248 TI - Dysregulation of EGFR Pathway in EphA2 Cell Subpopulation Significantly Associates with Poor Prognosis in Colorectal Cancer. AB - PURPOSE: EphA2 receptor is involved in multiple cross-talks with other cellular networks, including EGFR, FAK, and VEGF pathways, with which it collaborates to stimulate cell migration, invasion, and metastasis. Colorectal cancer (CRC) EphA2 overexpression has also been correlated to stem-like properties of cells and tumor malignancy. We investigated the molecular cross-talk and miRNAs modulation of the EphA2 and EGFR pathways. We also explored the role of EphA2/EGFR pathway mediators as prognostic factors or predictors of cetuximab benefit in patients with CRC. EXPERIMENTAL DESIGN: Gene expression analysis was performed in EphA2high cells isolated from CRC of the AOM/DSS murine model by FACS-assisted procedures. Six independent cohorts of patients were stratified by EphA2 expression to determine the potential prognostic role of a EphA2/EGFR signature and its effect on cetuximab treatment response. RESULTS: We identified a gene expression pattern (EphA2, Efna1, Egfr, Ptpn12, and Atf2) reflecting the activation of EphA2 and EGFR pathways and a coherent dysregulation of mir-26b and mir-200a. Such a pattern showed prognostic significance in patients with stage I III CRC, in both univariate and multivariate analysis. In patients with stage IV and WT KRAS, EphA2/Efna1/Egfr gene expression status was significantly associated with poor response to cetuximab treatment. Furthermore, EphA2 and EGFR overexpression showed a combined effect relative to cetuximab resistance, independently from KRAS mutation status. CONCLUSIONS: These results suggest that EphA2/Efna1/Egfr genes, linked to a possible control by miR-200a and miR-26b, could be proposed as novel CRC prognostic biomarkers. Moreover, EphA2 could be linked to a mechanism of resistance to cetuximab alternative to KRAS mutations. Clin Cancer Res; 23(1); 159-70. (c)2016 AACR. PMID- 27401250 TI - Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C. AB - PURPOSE: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. EXPERIMENTAL DESIGN: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. RESULTS: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2 MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. CONCLUSIONS: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. (c)2016 AACR. PMID- 27401252 TI - 25 Years of Cell Cycle Research: What's Ahead? AB - We have reached 25 years since the first molecular approaches to plant cell cycle. Fortunately, we have witnessed an enormous advance in this field that has benefited from using complementary approaches including molecular, cellular, genetic and genomic resources. These studies have also branched and demonstrated the functional relevance of cell cycle regulators for virtually every aspect of plant life. The question is - where are we heading? I review here the latest developments in the field and briefly elaborate on how new technological advances should contribute to novel approaches that will benefit the plant cell cycle field. Understanding how the cell division cycle is integrated at the organismal level is perhaps one of the major challenges. PMID- 27401251 TI - Endothelial Nitric Oxide Synthase Traffic Inducer (NOSTRIN) is a Negative Regulator of Disease Aggressiveness in Pancreatic Cancer. AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is refractory to available treatments. Delineating critical pathways, responsible for disease aggressiveness and therapeutic resistance, may identify effective therapeutic targets. We aimed to identify key pathways contributing to disease aggressiveness by comparing gene expression profiles of tumors from early-stage PDAC cases with extremely poor survival (<=7 months) and those surviving 2 years or more following surgical resection. EXPERIMENTAL DESIGN: Gene expression profiling was performed in tumors in a test cohort of PDAC (N = 50), which included short (<=7 months, N = 11) and long surviving (>=2 years, N = 14) patients, using affymetrix GeneChip Human 1.0 ST array. Key genes associated with disease aggressiveness were identified, using Cox regression, Kaplan-Meier, and pathway analyses with validations in independent cohorts for mechanistic and functional analyses. RESULTS: Gene expression profiling identified 1,820 differentially expressed genes between short and long survival groups with inflammatory gene network ranking first. Lower expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was associated with worst survival indicating its potential inhibitory role in disease progression. NOSTRIN overexpression suppressed migration and invasion of pancreatic cancer cells and enhanced sensitivity to chemotherapeutic drug gemcitabine. NOSTRIN inhibited production of nitric oxide (NO) by suppressing the activation of endothelial nitric oxide synthase (eNOS). Furthermore, miR-221, bound to the 3'UTR of NOSTRIN and suppressed its expression, and an increased miR 221 expression associated with poor survival in PDAC. CONCLUSIONS: Our findings showed that NOSTRIN is a potential negative regulator of disease aggressiveness, which may be targeted for designing improved treatment strategy in PDAC. Clin Cancer Res; 22(24); 5992-6001. (c)2016 AACR. PMID- 27401253 TI - Bidirectional Interaction between Phyllospheric Microbiotas and Plant Volatile Emissions. AB - Due to their antimicrobial effects and their potential role as carbon sources, plant volatile organic compound (VOC) emissions play significant roles in determining the characteristics of the microbial communities that can establish on plant surfaces. Furthermore, epiphytic microorganisms, including bacteria and fungi, can affect plant VOC emissions in different ways: by producing and emitting their own VOCs, which are added to and mixed with the plant VOC blend; by affecting plant physiology and modifying the production and emission of VOCs; and by metabolizing the VOCs emitted by the plant. The study of the interactions between plant VOC emissions and phyllospheric microbiotas is thus of great interest and deserves more attention. PMID- 27401254 TI - Associations between the neuron-specific glucocorticoid receptor (NR3C1) Bcl-1 polymorphisms and suicide in cancer patients within the first year of diagnosis. AB - BACKGROUND: Cancer diagnosis is associated with an increased suicide risk, particularly within the first 1 year after diagnosis of cancer. Abnormal function of the hypothalamic-pituitary-adrenal axis has been implicated in the pathophysiology of depression and suicide. We examined genetic associations of the functional Bcl-1 polymorphism of (rs41423247) neuron-specific glucocorticoid receptor (NR3C1) gene, with death by suicide in cancer patients. Suicides occurring within a year of cancer diagnosis ('early suicide') were considered separately from those suicides during the second or subsequent year ('late suicide') after cancer diagnosis. METHODS: The subjects consisted of 343 cancer patients admitted to a general hospital in Seoul, South Korea from 1996 to 2009, of which 182 had died by suicide and 161 were alive on December 31, 2009. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sample of patients with cancer. We conducted a case-control association analysis of Bcl-1 polymorphism of NR3C1 gene. RESULTS: Subjects carrying the GG genotype of Bcl-1 polymorphism were at increased risk of early suicide when compared to those carrying the CC genotype (OR 3.80, 95 % CI 1.02-14.16, p = .047). Similarly, those individuals carrying the GG genotype (recessive mode) had an increased risk of early suicide relative to the CC or CG genotype (OR 3.71, 95 % CI 1.03-13.43, p = .045). However, there were no differences in the genotype distributions of the NR3C1 Bcl-1 polymorphism between late suicide cases and controls. CONCLUSIONS: Our findings suggest that the NR3C1 Bcl-1 polymorphisms may be involved in the susceptibility to suicide within the first year after cancer diagnosis among cancer patients in Korean population. PMID- 27401255 TI - Regulatory Mechanisms of Vitamin D3 on Production of Nitric Oxide and Pro inflammatory Cytokines in Microglial BV-2 Cells. AB - Inhibition of pro-inflammatory functions of microglia has been considered a promising strategy to prevent pathogenic events in the central nervous system under neurodegenerative conditions. Here we examined potential inhibitory effects of nuclear receptor ligands on lipopolysaccharide (LPS)-induced inflammatory responses in microglial BV-2 cells. We demonstrate that a vitamin D receptor agonist 1,25-dihydroxyvitamin D3 (VD3) and a retinoid X receptor agonist HX630 affect LPS-induced expression of pro-inflammatory factors. Specifically, both VD3 and HX630 inhibited expression of mRNAs encoding inducible nitric oxide synthase (iNOS) and IL-6, whereas expression of IL-1beta mRNA was inhibited only by VD3. The inhibitory effect of VD3 and HX630 on expression of iNOS and IL-6 mRNAs was additive. Effect of VD3 and HX630 was also observed for inhibition of iNOS protein expression and nitric oxide production. Moreover, VD3 and HX630 inhibited LPS-induced activation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor kappaB (NF-kappaB). PD98059, an inhibitor of ERK kinase, attenuated LPS-induced nuclear translocation of NF-kappaB and induction of mRNAs for iNOS, IL-1beta and IL-6. These results indicate that VD3 can inhibit production of several pro-inflammatory molecules from microglia, and that suppression of ERK activation is at least in part involved in the anti inflammatory effect of VD3. PMID- 27401256 TI - Uncoupling Protein 2 (UCP2) Function in the Brain as Revealed by the Cerebral Metabolism of (1-13C)-Glucose. AB - The mitochondrial aspartate/glutamate transporter Aralar/AGC1/Slc25a12 is critically involved in brain aspartate synthesis, and AGC1 deficiency results in a drastic fall of brain aspartate levels in humans and mice. It has recently been described that the uncoupling protein UCP2 transports four carbon metabolites including aspartate. Since UCP2 is expressed in several brain cell types and AGC1 is mainly neuronal, we set to test whether UCP2 could be a mitochondrial aspartate carrier in the brain glial compartment. The study of the cerebral metabolism of (1-13C)-glucose in vivo in wild type and UCP2-knockout mice showed no differences in C3 or C2 labeling of aspartate, suggesting that UCP2 does not function as a mitochondrial aspartate carrier in brain. However, surprisingly, a clear decrease (of about 30-35 %) in the fractional enrichment of glutamate, glutamine and GABA was observed in the brains of UCP2-KO mice which was not associated with differences in either glucose or lactate enrichments. The results suggest that the dilution in the labeling of glutamate and its downstream metabolites could originate from the uptake of an unlabeled substrate that could not leave the matrix via UCP2 becoming trapped in the matrix. Understanding the nature of the unlabeled substrate and its precursor(s) as alternative substrates to glucose is of interest in the context of neurological diseases associated with UCP2. PMID- 27401258 TI - Characterization and longitudinal monitoring of serum progestagens and estrogens during normal pregnancy in the killer whale (Orcinus orca). AB - The secretory patterns of progestagens and estrogens were characterized throughout 28 normal pregnancies until two month post-partum in eleven killer whales. HPLC analysis of serum from different reproductive stages (luteal phase, EARLY, MID, and LATE pregnancy) identified three major immunoreactive progestagen peaks; progesterone (P4), 5alpha-pregnane-3,20-dione (5alpha-DHP) and pregnanediol, with 5alpha-DHP approximately half of that for P4 in the luteal phase, and EARLY, but approximately 2/3 of P4 during MID and LATE pregnancy. At birth, 5alpha-DHP was the only significant (>10% immunoreactivity) immunoreactive progestagen detected in placental (umbilical cord) serum. Maternal recognition of pregnancy appears to occur between day 21 and 28 post-ovulation when a significant deviation in progestagen concentrations between conceptive and non conceptive cycles was detected. Progestagen concentrations during pregnancy displayed a bimodal pattern with significant peaks (P<0.05) in EARLY (indexed month post-conception [IMPC] 2, 3, 4) and MID (IMPC 9, 10) before decreasing (P<0.05) over an 11day interval to luteal phase concentrations on the day of parturition. Among estrogens, estriol was secreted in the highest concentrations but only estrone (free and conjugated) and estradiol increased (P<0.001) during pregnancy, with peaks observed during the final month of gestation, and an influence (P<0.05) of fetal sex on estradiol production was detected. Collective findings indicate that P4 derived from the corpus luteum is the major biologically active progestagen during the luteal phase and pregnancy, and that 5alpha-DHP production, possibly from both luteal and placental sources, increases during the second half of pregnancy. PMID- 27401257 TI - Maitake Pro4X has anti-cancer activity and prevents oncogenesis in BALBc mice. AB - The understanding of the molecular mechanisms of the immune tolerance induced by the tumoral microenvironment is fundamental to prevent cancer development or to treat cancer patients using immunotherapy. Actually, there are investigations about "addressed-drugs" against cancer cells without affecting normal cells. It could be ideal to find selective and specific compounds that only recognize and destroy tumor cells without damaging the host normal cells. For thousands of years, mushrooms have been used for medicinal purposes because of their curative properties. D-Fraction, an extract of Maitake (from the edible Grifola frondosa mushroom), rich in beta-glucans, exert notable effects in the immune system. Until now, some published articles suggest that Maitake D-Fraction could have anti-tumoral activity, prevent oncogenesis and metastasis in some tumor types. However, there are no clear data about Maitake D-Fraction action on breast cancer prevention and its exact molecular mechanisms are not yet elucidated. The experiments were performed employing 25 female BALBc mice that were treated with and without Maitake D-Fraction Pro4X or Maitake Standard for 15 days by daily intraperitoneal injection. After treatment period, all mice were implanted with murine tumor cells LM3 to induce mammary tumorigenesis. Animals were checked weekly and killed after 46 days of LM3 transplant; percentage of cancer prevention, rate of tumor growing, and overall survival were determined. Under dissection, the internal organs were evaluated histologically and genetically by RT-PCR. We found that 5 mg/kg per day of Maitake D-Fraction Pro4X, administered dairy during 15 days to BALBc mice was able to block more than 60% breast cancer development. However, Maitake Standard prevents oncogenesis in 26% to respect control. In this work, we found that Maitake D-Fraction Pro4X, administered to BALBc mice, prevents breast carcinogenesis, block tumor invasiveness, reduce angiogenesis, and increase overall survival. PMID- 27401259 TI - Gonadotropin-releasing hormone and adipokinetic hormone/corazonin-related peptide in the female prawn. AB - Crustacean neuropeptides (NPs) play important roles in the regulation of most physiological activities, including growth, molting and reproduction. In this study, we have performed an in silico analysis of female prawn (Macrobrachium rosenbergii) neural transcriptomes to identify NPs not previously identified. We predict that approximately 1309 proteins are destined for the secretory pathway, many of which are likely post-translationally processed to generate active peptides. Within this neural secretome, we identified a gene transcript that encoded a precursor protein with striking similarity to a gonadotropin-releasing hormone (GnRH). We additionally identified another GnRH NP superfamily member, the adipokinetic hormone/corazonin-related peptide (ACP). M. rosenbergii GnRH and ACP were widespread throughout the nervous tissues, implicating them as potential neuromodulators. Furthermore, GnRH was found in non-neural tissues, including the stomach, gut, heart, testis and ovary, in the latter most prominently within secondary oocytes. The GnRH/corazonin receptor-like gene is specific to the ovary, whereas the receptor-like gene expression is more widespread. Administration of GnRH had no effect on ovarian development and maturation, nor any effect on total hemolymph lipid levels, while ACP administration decreased oocyte proliferation (at high dose) and stimulated a significant increase in total hemolymph lipids. In conclusion, our targeted analysis of the M. rosenbergii neural secretome has revealed the decapod GnRH and ACP genes. We propose that ACP in crustaceans plays a role in the lipid metabolism and the inhibition of oocyte proliferation, while the role of the GnRH remains to be clearly defined, possibly through experiments involving gene silencing. PMID- 27401260 TI - Cryosurvival of isolated testicular cells and testicular tissue of tench Tinca tinca and goldfish Carassius auratus following slow-rate freezing. AB - Experiments were carried out to test the efficiency of cryopreservation of whole testicular tissue in tench Tinca tinca and goldfish Carassius auratus and compare it to cryopreservation of isolated testicular cells. Additionally, effects of three cryoprotectants (dimethyl sulphoxyde - Me2SO, methanol - MeOH and ethylene glycol - EG) at three concentrations (1M, 2M and 3M) on post-thaw cell viability were assessed. Tissue pieces/isolated testicular cells were diluted in cryomedia and cryopreserved by slow-rate freezing (1 degrees C/min to -80 degrees C followed by a plunge into the liquid nitrogen). In both species Me2SO and EG generally yielded higher cryosurvival of early-stage germ cells than MeOH, while spermatozoa of neither species displayed such a pattern. In most cases a 3M>2M>1M viability pattern emerged in both species for both sample types regardless of the cryoprotectant used. Sample type (dissociated testicular cells vs testicular tissue) did not seem to affect viability rates of tench early-stage germ cells and goldfish spermatozoa, while the opposite was observed for tench spermatozoa and goldfish early-stage germ cells. Additionally, through histological analysis we displayed that tissue structure mainly remained unaltered after thawing in goldfish. These results indicate that cryopreservation of whole testicular tissue is indeed a valid alternative method to cryopreservation of dissociated testicular cells. Early-stage germ cells obtained from cryopreserved testis can be further used in different purposes such as transplantation into suitable donors while viable sperm might be used for fertilization when feasible. PMID- 27401261 TI - Hypothalamus-pituitary-gonad axis of rainbow trout (Oncorhynchus mykiss) during early ovarian development and under dense rearing condition. AB - The objective of this study was to determine the hypothalamus-pituitary-gonad (HPG) axis of female rainbow trout (Oncorhynchus mykiss) during early ovarian development and under high rearing density. Trouts were sampled from 240 (ovarian stage II) to 540 (ovarian stage IV) days following hatching (DFH) as control group (Ctrl, 4.6-31.1kg/m(3)) to determine HPG axis during early ovarian development. Trouts from the same batch of fertilized eggs were reared in two higher densities during 240-540 DFH as stocking density 1 and 2 (SD1, 6.6 40.6kg/m(3); SD2, 8.6-49.3kg/m(3)) to elucidate effects of high density on reproductive parameters. Dopamine, E2 (estradiol), 17alpha,20beta-P (17alpha,20beta-dihydroxy4-pregnen-3-one) and P4 (progesterone) were evaluated by radioimmunoassay or ELISA. mRNA expression of hypothalamic gnrh-1, -2 (gonadotropin-releasing hormone-1, -2), pituitary gonadotropins (fsh/lh, follicle stimulating hormone/luteinizing hormone) and their cognate receptors (fshr/lhr) in ovaries were examined by qRT-PCR. Our findings demonstrated mRNA expression of hypothalamic sgnrh-1, pituitary fsh and ovarian fshr increased in early ovarian development (360 DFH). Serum 17alpha,20beta-P and pituitary lh mRNA expression first increased when trouts were in ovarian stage III (420 DFH). Ovaries were at different stages when reared in different densities. Long-term high density treatment (over 31.7kg/m(3)) resulted in decreased hypothalamic sgnrh-1, pituitary fsh, ovarian fshr, serum E2, and increased hypothalamus gnrh-2 and serum dopamine during vitellogenin synthesis, suggesting HPG of rainbow trout might be retarded under dense rearing condition. PMID- 27401263 TI - Paternal identity impacts embryonic development for two species of freshwater fish. AB - Paternal, compared to maternal, contributions were believed to have only a limited influence on embryonic development and larval fitness traits in fishes. Therefore, the perspective of male influence on early life history traits has come under scrutiny. This study was conducted to determine parental effects on the rate of eyed embryos of Ide Leuciscus idus and Northern pike Esox lucius. Five sires and five dams from each species were crossed using a quantitative genetic breeding design and the resulting 25 sib groups of each species were reared to the embryonic eyed stage. We then partition variation in embryonic phenotypic performance to maternal, paternal, and parental interactions using the Restricted Maximum Likelihood (REML) model. Results showed that paternal, maternal, and the paternal*maternal interaction terms were highly significant for both species; clearly demonstrating that certain family combinations were more compatible than others. Paternal effects explained 20.24% of the total variance, which was 2-fold higher than the maternal effects (10.73%) in Ide, while paternal effects explained 18.9% of the total variance, which was 15-fold higher than the maternal effects (1.3%) in Northern pike. Together, these results indicate that male effects are of major importance during embryonic development for these species. Furthermore, this study demonstrates that genetic compatibility between sires and dams plays an important role and needs to be taken into consideration for reproduction of these and likely other economically important fish species. PMID- 27401264 TI - Methyltestosterone alters sex determination in the American alligator (Alligator mississippiensis). AB - Effects of xenobiotics can be organizational, permanently affecting anatomy during embryonic development, and/or activational, influencing transitory actions during adulthood. The organizational influence of endocrine-disrupting contaminants (EDC's) produces a wide variety of reproductive abnormalities among vertebrates that exhibit temperature-dependent sex determination (TSD). Typically, such influences result in subsequent activational malfunction, some of which are beneficial in aquaculture. For example, 17-alphamethyltestosterone (MT), a synthetic androgen, is utilized in tilapia farming to bias sex ratio towards males because they are more profitable. A heavily male-biased hatchling sex ratio is reported from a crocodile population near one such tilapia operation in Guanacaste, Costa Rica. In this study we test the effects of MT on sexual differentiation in American alligators, which we used as a surrogate for all crocodilians. Experimentally, alligators were exposed to MT in ovo at standard ecotoxicological concentrations. Sexual differentiation was determined by examination of primary and secondary sex organs post hatching. We find that MT is capable of producing male embryos at temperatures known to produce females and demonstrate a dose-dependent gradient of masculinization. Embryonic exposure to MT results in hermaphroditic primary sex organs, delayed renal development and masculinization of the clitero-penis (CTP). PMID- 27401262 TI - Alterations in eicosanoid composition during embryonic development in the chorioallantoic membrane of the American alligator (Alligator mississippiensis) and domestic chicken (Gallus gallus). AB - Eicosanoids are signaling lipids known to regulate several physiological processes in the mammalian placenta, including the initiation of parturition. Though all amniotes construct similar extraembryonic membranes during development, the composition and function of eicosanoids in extraembryonic membranes of oviparous reptiles is largely unknown. The majority of effort placed in eicosanoid investigations is typically targeted toward defining the role of specific compounds in disease etiology; however, comprehensive characterization of several pathways in eicosanoid synthesis during development is also needed to better understand the complex role of these lipids in comparative species. To this end, we have examined the chorioallantoic membrane (CAM) of the American alligator (Alligator mississippiensis) and domestic chicken (Gallus gallus) during development. Previously, our lab has demonstrated that the CAM of several oviparous species shared conserved steroidogenic activity, a feature originally attributed to mammalian amniotes. To further explore this, we have developed a liquid chromatography/tandem mass spectrometry method that is used here to quantify multiple eicosanoids in the CAM of two oviparous species at different stages of development. We identified 18 eicosanoids in the alligator CAM; the cyclooxygenase (COX) pathway showed the largest increase from early development to later development in the alligator CAM. Similarly, the chicken CAM had an increase in COX products and COX activity, which supports the LC-MS/MS analyses. Jointly, our findings indicate that the CAM tissue of an oviparous species is capable of eicosanoid synthesis, which expands our knowledge of placental evolution and introduces the possibility of future comparative models of placental function. PMID- 27401265 TI - DNA damage and differential gene expression associated with physical stress in gilthead seabream (Sparus aurata). AB - Fish stress may result in inhibition of reproduction, development and growth. Thus, appropriate indices should be developed to accurately define the physiological plasticity of fish, in terms of coping with stress. Sea bream individuals were subjected to physical stress (fasting and confinement). DNA fragmentation of liver cells was assessed, in addition to gene expression of selected genes and plasma cortisol levels determination. Stress response was characterized with significant temporal alterations. Increased DNA fragmentation was observed as an aftereffect of physical stress and consequently gene expression of tp53 was stimulated. The expression pattern of glucocorticoid receptor (nr3c1) was directly correlated with plasma cortisol. Furthermore, glucokinase (gk) gene expression was considerably upregulated under acute stress, depicting putative energetic demands. Finally, igf1 downregulation during stress, reflects the suppression of the GH/IGF axis and the substantial stress effects on growth. To conclude, most of the indices described in the present study could be synergistically used, in order to robustly quantify physical stress in marine teleosts. PMID- 27401266 TI - Orthogonal photoswitching in a multifunctional molecular system. AB - The wavelength-selective, reversible photocontrol over various molecular processes in parallel remains an unsolved challenge. Overlapping ultraviolet visible spectra of frequently employed photoswitches have prevented the development of orthogonally responsive systems, analogous to those that rely on wavelength-selective cleavage of photo-removable protecting groups. Here we report the orthogonal and reversible control of two distinct types of photoswitches in one solution, that is, a donor-acceptor Stenhouse adduct (DASA) and an azobenzene. The control is achieved by using three different wavelengths of irradiation and a thermal relaxation process. The reported combination tolerates a broad variety of differently substituted photoswitches. The presented system is also extended to an intramolecular combination of photoresponsive units. A model application for an intramolecular combination of switches is presented, in which the DASA component acts as a phase-transfer tag, while the azobenzene moiety independently controls the binding to alpha-cyclodextrin. PMID- 27401268 TI - Calcifications in the carotid siphon inversely associate with cognitive performance in stroke-free community dwellers living in rural Ecuador (The Atahualpa Project). AB - We aimed to assess whether carotid siphon calcifications (as seen on computed tomography) are associated with worse performance in the Montreal Cognitive Assessment in 584 stroke-free individuals living in rural Ecuador. Using mean Montreal Cognitive Assessment score of subjects with Grade 1 calcifications (23.1 +/- 4.2) as the referent category, fully adjusted generalized linear models showed significant associations between severity of carotid siphon calcifications and cognitive performance (mean Montreal Cognitive Assessment scores: 20.2 +/- 4.8 for Grade 2 (p = 0.004), 19.7 +/- 5.3 for Grade 3 (p = 0.0001), and 18.8 +/- 4.1 for Grade 4 (p = 0.02)). Predictive Montreal Cognitive Assessment score margins were higher in individuals with Grade 1 calcifications than in other groups. This study shows an inverse relationship between calcium content in the carotid siphon and cognitive performance in Amerindians. PMID- 27401267 TI - Brain perfusion in dementia with Lewy bodies and Alzheimer's disease: an arterial spin labeling MRI study on prodromal and mild dementia stages. AB - BACKGROUND: We aimed to describe specific changes in brain perfusion in patients with dementia with Lewy bodies (DLB) at both the prodromal (also called mild cognitive impairment) and mild dementia stages, relative to patients with Alzheimer's disease (AD) and controls. METHODS: Altogether, 96 participants in five groups (prodromal DLB, prodromal AD, DLB with mild dementia, AD with mild dementia, and healthy elderly controls) took part in an arterial spin labeling MRI study. Three analyses were performed: a global perfusion value comparison, a voxel-wise analysis of both absolute and relative perfusion, and a linear discriminant analysis. These were used to assess the global decrease in perfusion, regional changes, and the sensitivity and specificity of these changes. RESULTS: Patterns of perfusion in DLB differed from AD and controls in both the prodromal stage and dementia, DLB having more deficits in frontal, insular, and temporal cortices whereas AD showed reduced perfusion in parietal and parietotemporal cortices. Decreases but also increases of perfusion in DLB relative to controls were observed in both absolute and relative measurements. All these regional changes of perfusion classified DLB patients with respect to either healthy controls or AD with sensitivity from 87 to 100 % and specificity from 90 to 96 % depending on the stage of the disease. CONCLUSIONS: Our results are consistent with previous studies. We extend the scope of those studies by integrating prodromal DLB patients and by describing both hypo- and hyperperfusion in DLB. While decreases in perfusion may relate to functional impairments, increases might suggest a functional compensation of some brain areas. PMID- 27401270 TI - Low incidence of D alloimmunization among patients with a serologic weak D phenotype after D+ transfusion. AB - BACKGROUND: By consensus definition, the red blood cells (RBCs) of patients that react weak to 2+ in the serologic D test are classified as having the serologic weak D phenotype (weak D). The risk of D alloimmunization in patients with weak D is not well studied. This study retrospectively determined the incidence of D alloimmunization in patients with weak D who received D+ blood products. STUDY DESIGN AND METHODS: Patient records at four institutions were reviewed. Eligible patients had at least 1 D typing result with agglutination strength that was weak to 2+ result in gel or tube (Institutions 1-3) or weak to 2+ result in solid phase or a positive tube weak D test using antihuman globulin reagent (Institution 4). All patients received at least 1 D+ allogeneic RBC or platelet transfusion and had a subsequent antibody detection test performed at least 30 days after the first D+ transfusion. RESULTS: The incidence of alloanti-D formation was 0.15% (6/4011, at Institutions 1-3) and 5.1% (3/59, at Institution 4; these incidences were significantly different [p = 0.0002]). There were 0.15% (6/4011) patients who had autoanti-D detected; all were at Institutions 1 to 3. CONCLUSIONS: Until RHD genotyping is widely available, these data support the fact that patients with serologic weak D may be transfused with D+ RBCs if an urgent transfusion is required. At Institution 4, inclusion of a higher proportion of black patients compared to the other institutions may have affected the incidence of alloimmunization by perhaps including partial D recipients who are at risk of forming D antibodies. PMID- 27401271 TI - Oxidized Low-Density Lipoprotein-beta2-Glycoprotein I Complex But Not Free Oxidized LDL Is Associated With the Presence and Severity of Coronary Artery Disease. AB - Oxidized low-density lipoprotein (oxLDL) and beta2-glycoprotein I (beta2GPI) have been identified in human atherosclerotic lesions and when complexed have been implicated as a pro-atherothrombotic antigen. We examined the association of free oxLDL and oxLDL-beta2GPI complex in patients with coronary artery disease who underwent elective cardiac catheterization. Serum was collected from patients with suspected coronary artery disease immediately before elective cardiac catheterization who were either treated (n = 385) or not treated (n = 150) with statins and from healthy volunteers (n = 134). OxLDL and oxLDL-beta2GPI complex levels were determined by enzyme-linked immunosorbent assay. Disease severity was defined angiographically as none-minimal (<20%), moderate (20% to 75%), and severe (>75%) luminal diameter obstruction of any major coronary vessel. Both oxLDL and oxLDL-beta2GPI complex were lower in patients on statins (p <0.001). In statin-naive patients, oxLDL-beta2GPI complex, but not free oxLDL, was associated with severe coronary artery disease (p = 0.036). However, no association was observed in patients on statins. LDL4 and triglycerides increased with oxLDL beta2GPI complex quartiles (p = 0.001). OxLDL-beta2GPI complex (>0.32 U/ml) was predictive of severe atherosclerosis by receiver-operating characteristic curve analysis in statin-naive patients (area under the curve 0.66, p = 0.002). In conclusion, oxLDL-beta2GPI appears more predictive of coronary artery disease severity than oxLDL alone in statin-naive patients. PMID- 27401272 TI - Noninvasive Assessment of Vascular Function in Postoperative Cardiovascular Disease (Coarctation of the Aorta, Tetralogy of Fallot, and Transposition of the Great Arteries). AB - Using noninvasive techniques, we sought to assess arterial stiffness, impedance, hydraulic power, and efficiency in children with postoperative tetralogy of Fallot (TOF), coarctation of the aorta (COA), and transposition of the great arteries (TGAs). Results were compared with those of healthy peers. Fifty-five children with repaired congenital heart disease (24 TOFs, 20 COAs, and 11 TGAs) were compared with 55 age-matched control subjects (CTRL). Echocardiographic Doppler imaging and carotid artery applanation tonometry were preformed to measure aortic flow, dimensions, and calculate pulse wave velocity, vascular impedance and arterial stiffness indexes, hydraulic power (mean and total), and hydraulic efficiency (HE) which were calculated using standard fluid dynamics equations. All congenital heart disease subgroups had higher pulse wave velocity than CTRL. Only the COA group had higher characteristic impedance. Mean power was higher in TGA than in CTRL and TOF, and total power was higher in TGA than in CTRL and TOF. Hydraulic efficiency was higher in TOF than in COA and TGA. In conclusion, children with TOF, COA, and TGA have stiffer aortas than CTRL. These changes may be related to intrinsic aortic abnormalities, altered integrity of the aorta due to surgical repair, and/or acquired postsurgery. These patients may be at increased long-term cardiovascular risk, and long-term follow-up is important for monitoring and assessment of efforts to reduce risk. PMID- 27401273 TI - Efficacy and Safety of Endoscopic Balloon Dilation for Upper Gastrointestinal Strictures of Crohn's Disease. AB - BACKGROUND: Few articles focused on endoscopic balloon dilation (EBD) in the management of Crohn's strictures in the upper gastrointestinal (GI) tract. AIMS: The purpose of this study was to evaluate the long-term efficacy and safety of EBD for Crohn's strictures in the upper GI tract and to determine early predictors of response and surgical intervention. METHODS: All eligible patients who underwent EBD for Crohn's strictures in the upper GI tract were retrospectively reviewed. The long-term success was defined as the recovery of normal diets without surgical intervention over the follow-up period. In order to seek early predictors, patients who achieved long-term success were compared with those who didn't. RESULTS: A total of 67 dilations of upper GI strictures were performed between June 2011 and March 2015 on 24 patients (mean age 25.6 +/- 6.7, 20 male) with Crohn's disease. Technical success was achieved in 62 of 67 dilations (92.5 %) with a complication rate of 3 %. After the median follow-up period of 23.0 months (range 6.2-51.2 months), nine patients underwent surgical intervention, nine patients were still depending on tube feeding; in the meantime, only six (25 %) patients achieved long-term success. Additionally, patients who remained 1 month intervention-free (55.6 vs. 5.9 %, P = 0.015) were more likely to achieve long-term success. CONCLUSIONS: EBD was a safe procedure, but not a potent therapy for Crohn's upper GI strictures. Meanwhile, 1-month response could serve as an early predictor of the long-term response. PMID- 27401274 TI - Ileal or Anastomotic Location of Lesions Does Not Impact Rate of Postoperative Recurrence in Crohn's Disease Patients Classified i2 on the Rutgeerts Score. AB - BACKGROUND: The Rutgeerts score with 5 grades of severity (i0-i4) is a suitable endoscopic model to predict clinical recurrence following ileocolonic resection in Crohn's disease (CD). Definition of grade i2 includes lesions confined to the ileocolonic anastomosis (i2a) or moderate lesions on the neo-terminal ileum (i2b). The aim of the present study was to evaluate the probability of clinical recurrence in i2a and i2b patients. METHODS: This multicenter retrospective study included all CD patients classified i2 at the first postoperative ileocolonoscopy. The primary outcome was to evaluate the probability of clinical recurrence in patients classified i2a and i2b. The secondary outcome was to compare the rate of global recurrence of CD. RESULTS: Fifty patients were included: 23 were classified i2a and 27 were classified i2b. The median duration of follow-up was 40 (18.0-80.4) months in the i2a group and 53.5 (25.0-69.0) months in the i2b group (p = 0.9). The probability of clinical recurrence was not significantly different between patients classified i2a and i2b (p = 0.64). Median time to clinical recurrence after the first ileocolonoscopy and probability of global CD recurrence were not different between the two groups (p >= 0.19). CONCLUSIONS: The rate of clinical postoperative recurrence is not different in i2a and i2b patients. These results suggest that the same therapeutic strategy should be used in all patients classified i2 on the Rutgeerts score whatever the location of postoperative CD recurrence. PMID- 27401275 TI - Truncating and missense PPM1D mutations in early-onset and/or familial/hereditary prostate cancer patients. AB - Truncating activating mutations in the last exon of PPM1D have been described in patients with breast, ovarian, colorectal and non-small cell lung cancer, but recent data indicate that they may be associated with previous chemotherapy. In this study we evaluated the prevalence of PPM1D mutations in white blood cells (WBC) of 462 patients with early-onset and/or familial/hereditary prostate cancer (PrCa) by sequencing the coding region of exon 6. Two truncating mutations were found in two patients (0.4%), both treated with androgen-ablation therapy but no chemotherapy prior to blood collection. Next generation sequencing analysis showed that the truncating variants were present in 21.4% and 32.4% of the reads, indicating that they were in mosaic in WBC, something that was confirmed by its absence in a different tissue from one of these patients. Additionally, nine patients (1.95%) were found to harbor non-synonymous germline mutations, with three patients sharing the same missense variant, c.1607G > A, p.Arg536Lys. This variant was predicted to be deleterious by different in silico tools and was not found in the 293 male control subjects tested. Large cohorts and/or functional evaluation are needed to clarify the nature of the truncating mosaic mutations in PrCa patients treated with and without androgen-ablation therapy and to evaluate the contribution of the recurrent missense variant to the risk of developing PrCa. (c) 2016 Wiley Periodicals, Inc. PMID- 27401276 TI - Variations in the patterns of soil organic carbon mineralization and microbial communities in response to exogenous application of rice straw and calcium carbonate. AB - The addition of exogenous inorganic carbon (CaCO3) and organic carbon has an important influence on soil organic carbon (SOC) mineralization in karst soil, but the microbial mechanisms underlying the SOC priming effect are poorly understood. We conducted a 100-day incubation experiment involving four treatments of the calcareous soil in southwestern China's karst region: control, (14)C-labeled rice straw addition, (14)C-labeled CaCO3 addition, and a combination of (14)C-labeled rice straw and CaCO3. Changes in soil microbial communities were characterized using denaturing gradient gel electrophoresis with polymerase chain reaction (PCR-DGGE) and real-time quantitative PCR (q-PCR). Both (14)C-rice straw and Ca(14)CO3 addition stimulated SOC mineralization, suggesting that organic and inorganic C affected SOC stability. Addition of straw alone had no significant effect on bacterial diversity; however, when the straw was added in combination with calcium carbonate, it had an inhibitory effect on bacterial and fungal diversity. At the beginning of the experimental period, exogenous additives increased bacterial abundance, although at the end of the 100-day incubation bacterial community abundance had gradually declined. Incubation time, exogenous input, and their interaction significantly affected SOC mineralization (in terms of priming and the cumulative amount of mineralization), microbial biomass carbon (MBC), and microbial community abundance and diversity. Moreover, the key factors influencing SOC mineralization were MBC, bacterial diversity, and soil pH. Overall, these findings support the view that inorganic C is involved in soil C turnover with the participation of soil microbial communities, promoting soil C cycling in the karst region. PMID- 27401277 TI - Ecological response to hydrological variability and catchment development: Insights from a shallow oxbow lake in Lower Mississippi Valley, Arkansas. AB - The ecological response of shallow oxbow lakes to variability in hydrology and catchment development in large river floodplain ecosystems (RFE) in Arkansas remains largely unknown. Investigating these responses will advance our understanding of ecological evolution of oxbow lakes in response to the major environmental drivers, which will establish baseline conditions required to develop effective management practices for RFE. In this pilot study, we examined the potential of using a dated surface sediment core from Adams Bayou, a floodplain lake located within the Cache-Lower White River Ramsar site in SE Arkansas. Stratigraphic records of diatoms and sediment geochemistry were used to ascertain variation in Adams Bayou's ecological condition. During 1968-2008, in response to hydrological and anthropogenic changes, Adams Bayou's diatom assemblages progressed from predominantly benthic (Gomphonema parvulum and Meridion circulare) to primarily planktonic assemblage (Aulacoseira granulata and Cyclotella meneghiniana), along with a decrease in magnetic susceptibility (k) and % silt. Statistical analyses reveled that during 1968-2000, higher hydrological connectivity and catchment alterations drove Adams Bayou's ecosystem. After 2000, lower hydrological connectivity and increase in cultivation were the major drivers. The potential impact of increasing air temperature was also noted. The shift in Adams Bayou from a connected, clear, mesotrophic state to a relatively isolated, turbid and nutrient enriched state is consistent with regime shift models and highlights its sensitivity to a combination of environmental stresses prevalent in the catchment. Although fluvial systems pose challenges in establishing clear chronologies, oxbow lake sediments can be a effective paleoecological archives. Our work provides clear evidence for the change in the ecological character of this wetland of international significance and flags the need for a wider assessment of water bodies across this site under obligations to the Ramsar Convention. PMID- 27401278 TI - Improving SWAT for simulating water and carbon fluxes of forest ecosystems. AB - As a widely used watershed model for assessing impacts of anthropogenic and natural disturbances on water quantity and quality, the Soil and Water Assessment Tool (SWAT) has not been extensively tested in simulating water and carbon fluxes of forest ecosystems. Here, we examine SWAT simulations of evapotranspiration (ET), net primary productivity (NPP), net ecosystem exchange (NEE), and plant biomass at ten AmeriFlux forest sites across the U.S. We identify unrealistic radiation use efficiency (Bio_E), large leaf to biomass fraction (Bio_LEAF), and missing phosphorus supply from parent material weathering as the primary causes for the inadequate performance of the default SWAT model in simulating forest dynamics. By further revising the relevant parameters and processes, SWAT's performance is substantially improved. Based on the comparison between the improved SWAT simulations and flux tower observations, we discuss future research directions for further enhancing model parameterization and representation of water and carbon cycling for forests. PMID- 27401279 TI - Albedo indicating land degradation around the Badain Jaran Desert for better land resources utilization. AB - Surface albedo is an easy access parameter in reflecting the status of both human disturbed soil and indirectly influenced area, whose characteristic is an important indicator in sustainable development under the background of global climate change. In this study, we employed meteorological data, MODIS 8-day BRDF/Albedo and LAI products from 2000 to 2014 to show the amelioration and mechanism around the Badain Jaran Desert. Results showed that the human-dominated afforestation activities significantly increased the leaf area index (LAI) in summer and autumn. Lower reflectance at visible band was sensed inside the desert compared with the ecozone and the lowest albedo at forested area. The contribution of soil and vegetation reflectance to surface albedo determined the linear sensitivity of albedo to LAI variation. Decreased albedo dominated the spatial-temporal pattern of the Badain Jaran Desert. This study suggested that surface albedo can be regarded as a useful index in indicating the change process and evaluating the sustainable development of biological management around the Badain Jaran Desert. PMID- 27401280 TI - Multi-year air monitoring of legacy and current-use brominated flame retardants in an urban center in northeastern China. AB - The occurrence and temporal trends of polybrominated diphenyl ethers (PBDEs) and non-PBDE brominated flame retardants (NBFRs) were investigated in an urban atmosphere of Northeast China in consecutive six years (2008-2013). Among all chemicals, BDE-209, l,2,5,6,9,10-hexabromocyclododecane (HBCD), and decabromodiphenylethane (DBDPE) were the three most dominant compounds. During the period, the levels of pentabromodiphenyl ethers in the gas-phase and octabromodiphenyl ethers in the particle-phase significantly decreased, while the levels of BDE-209 and NBFRs increased in either the gas-phase or particle-phase. Ambient temperature was the most significant variable that influenced the gas phase and particle-phase concentrations of BFRs, followed by wind speed and relative humidity. A stronger temperature dependence of the atmospheric concentrations was found for lower mass BFRs. Gas-particle partitioning studies suggested PBDEs in the urban atmosphere of Northeast China were at steady-state. Steady-state equation can also well describe the partitioning behavior for NBFRs, suggesting that the atmospheric partitioning behaviors of NBFRs were similar to those of PBDEs. PMID- 27401281 TI - Effect of water-sediment regulation of the Xiaolangdi reservoir on the concentrations, characteristics, and fluxes of suspended sediment and organic carbon in the Yellow River. AB - Water-sediment regulation (WSR) of the Xiaolangdi Reservoir in the Yellow River is different from other water conservancy projects, with sediment resuspending along the river downstream of the reservoir during water regulation while some suspended sediment depositing during sediment regulation. In this study, samples were collected before, during, and after WSR to investigate the effect of WSR on the suspended sediment and organic carbon downstream of the reservoir. The suspended sediment concentration ([SPS]) increased with the river flow velocity (V) as a power function ([SPS]=1.348V(2.519)) during the three periods. The suspended sediment grain size decreased along the river during water and sediment regulations and after WSR; they were generally below 200MUm with the fine particles (<50MUm) of 68.0%-93.7% and positively correlated with the flow velocity. The black carbon content in suspended sediment elevated along the river during both water and sediment regulations, and it increased with 2-50MUm fraction during water regulation and with <2MUm fraction during sediment regulation, suggesting that black carbon mainly exists in fine particles and is influenced by both suspended sediment source and characteristics. There was no significant difference in dissolved organic carbon (DOC) concentration during water regulation, sediment regulation, and after WSR, inferring that the effect of sediment resuspension/deposition on DOC concentration was insignificant. The contribution of DOC flux (27.3%) during WSR period to the annual flux was comparable to that (22.6%) of water, but lower than the sediment (32.5%) and particulate organic carbon (POC) (49.5%). This study suggests that WSR will exert significant influence on the concentrations, characteristics and fluxes of POC (p<0.05) and sediment (p<0.05) but have no significant influence on DOC (p>0.1) of the Yellow River. PMID- 27401282 TI - Products and mechanisms of the heterogeneous reactions of ozone with commonly used pyrethroids in the atmosphere. AB - The heterogeneous reactions of gas-phase ozone and two pyrethroid pesticides, deltamethrin and permethrin, which are the most frequently applied insecticides today, has been investigated. Tentative identifications of heterogeneous ozonolysis products of both pesticides reveal that the reaction mechanisms differ and are mainly influenced by the presence of the cyano moiety at the alpha position of deltamethrin (pyrethroid type II). The mechanism study also suggests the important role of water. Finally, several of the degradation products emerged from the ozonolysis of deltamethrin and permethrin may pose further health and environmental hazard due to their higher toxicity, such as phosgene for permethrin, and bromophosgene, 3-phenoxybenzaldehyde (3-PBA) and fulminic acid for deltamethrin. The results obtained in this study can contribute to better describe the atmospheric fate of pesticides in the particle phase. PMID- 27401283 TI - Structural properties of fracture haematoma: current status and future clinical implications. AB - Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401284 TI - Reply to the letter "Long term effects of nocturnal hypoxia and urinary uric acid excretion: How much linked to COPD and OSAS?". PMID- 27401285 TI - Panax quinquefolium saponin combined with dual antiplatelet drugs inhibits platelet adhesion to injured HUVECs via PI3K/AKT and COX pathways. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolium saponin (PQS) is the active component extracted from traditional Chinese medicine Panax quinquefolius L. and has been widely used as a supplement to dual antiplatelet drugs (DA) for treatment of coronary artery disease (CAD) for two decades; however, the efficacy of PQS combined with DA against platelet adhesion to endothelial cells (ECs), an essential step in thrombosis, remains unclear. AIM OF THE STUDY: To compare PQS combined with DA and DA alone in inhibiting platelet adhesion to injured human umbilical vein endothelial cells (HUVECs) and to explore the possible mechanisms focusing on PI3K/AKT, COX-2/6-keto-PGF1alpha, and COX-1/TXB2 pathways. METHODS: HUVECs injured by oxidized low-density lipoprotein (ox-LDL) were randomly allocated into control, model, DA, PQS+DA (P+DA), LY294002 (a PI3K inhibitor)+DA (L+DA), and LY294002+PQS+DA (LP+DA) groups. HUVEC apoptosis, platelet adhesion to injured HUVECs, and platelet CD62p expression were assayed by fluorescence activated cell sorting (FACS). The concentrations of 6-keto-PGF1alpha and TXB2 in the supernatant were measured by radioimmunoassay. Protein expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT, AKT, COX-1, and COX-2 in both platelets and HUVECs was evaluated by western blot. RESULTS: Compared to DA alone, PQS combined with DA reduced platelet adhesion to HUVECs and HUVEC apoptosis more potently, increased the concentration of supernatant 6-keto PGF1alpha and up-regulated phospho-AKT protein in HUVECs. LY294002 mitigated the effects of PQS on HUVEC apoptosis and platelet adhesion. CONCLUSIONS: These findings show that PQS as a powerful supplement to DA, attenuated HUVEC apoptosis and improved the DA-mediated reduction of platelet adhesion to injured HUVECs and the underlying mechanisms may be associated with PI3K/AKT and COX pathways in HUVECs and platelets. PQS might provide a new complementary approach to improve the prognosis of thrombotic diseases in future. PMID- 27401286 TI - The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. MATERIALS AND METHODS: T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group--vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. RESULTS: Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI3K/Akt signaling pathway of T2DM rats in liver were significantly up regulated, while the total IRS2, PI3K, and Akt protein had no obvious changes. CONCLUSIONS: The results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver. PMID- 27401287 TI - Effect of standardized extract of Bacopa monnieri (CDRI-08) on testicular functions in adult male mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (BM) has been used in India since the time of Rig-Veda for augmentation of learning, memory, brain health etc. AIM OF THE STUDY: The memory augmenting effect of BM is well documented. CDRI-08 is a standardized extract of Bacopa monnieri, but its effect on the male reproductive health has not been investigated. Therefore, the aim of the present study was to examine the effect of CDRI-08 administration on the male reproductive organs with special emphasis on testis in adult mice. MATERIALS AND METHODS: CDRI-08, containing at least 55% bacosides (the major constituent of BM), was investigated for its effect on testicular functions in adult Parkes (P) mice. A suspension of CDRI-08 was orally administered in doses of 40 and 80mgkg-1 body weight day-1 for 28 days and various male reproductive end points were evaluated. RESULTS: Compared to control, CDRI-08 treatment caused a significant increase (p<0.05) in spermatogenic cell density (germinal epithelial height: control, 55.03+/-4.22 vs 40mg, 67.15+/-2.65 and 80mg, 69.93+/-3.76; and tubular diameter: control, 206.55+/-2.62 vs 80mg, 253.23+/-12.19), PCNA index (control, 59.85+/-2.09 vs 40mg, 82.17+/-1.56 and 80mg, 84.05+/-3.51) and in steroidogenic indices in the testis, and in sperm viability (control, 0.67+/-0.010 vs 80mg, 0.80+/-0.04) in cauda epididymidis of the treated mice. On the other hand, however, the same treatment caused a significant decrease (p<0.05) in abnormal sperm morphology (control, 21.72+/-1.06 vs 40mg, 10.63+/-1.50 and 80mg, 15.86+/-0.87) in cauda epididymidis, and in lipid peroxidation level in testis of the treated mice compared to controls. CONCLUSION: The results suggest that treatment with CDRI-08 extract improves sperm quality, and spermatogenic cell density and steroidogenic indices in the testis of P mice. PMID- 27401288 TI - In vivo and in vitro anti-inflammatory effects of Zao-Jiao-Ci (the spine of Gleditsia sinensis Lam.) aqueous extract and its mechanisms of action. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Zao-Jiao-Ci (ZJC), as the spine of Chinese Honey locust (Gleditsia sinensis Lam.), is traditionally used as Chinese medicine to reduce inflammation. AIM OF THE STUDY: The present study aimed to investigate an anti-inflammatory effect of ZJC aqueous extract both in vitro and in vivo, as well as its underlying mechanisms. MATERIALS AND METHODS: Anti-inflammatory effect of ZJC aqueous extract was evaluated by using carrageenan-induced paw edema in rats. In addition, the inhibitory effects of ZJC on nitric oxide production, intracellular reactive oxygen species production, pro-inflammatory mediator expression and prostaglandin E2 (PGE2) production were determined by using LPS-activated RAW 264.7 cells. The anti-oxidant activity of ZJC was assessed using 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid assay. RESULTS: ZJC aqueous extract showed significant suppressive effect on paw edema in rats at 100mg/kg. Moreover, ZJC aqueous extract decreased the expression of cyclooxygenase (COX)-2 and significantly decreased the PGE2, tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 production in LPS-activated macrophages in dose-dependent manners. ZJC aqueous extract inhibited the mRNA expression of these inflammatory cytokines as well. Furthermore, ZJC aqueous extract was found as an anti-oxidant and could inhibit ROS production in the LPS induced cells. CONCLUSIONS: These findings show the potential of ZJC aqueous extract as a naturally occurring COX-2 inhibitor to reduce inflammation. PMID- 27401289 TI - Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH. AIM OF THE STUDY: The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated. MATERIALS AND METHODS: The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150-200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175ug/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively. RESULTS: MCT caused right ventricular hypertrophy (0.58+/-0.05 vs 0.31+/-0.05; P<0.001 vs. control) and increase in RVSP (33.5+/-1.5 vs 22.3+/ 4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49+/-0.05 vs 0.32+/-0.06; P<0.001) which was prevented by sildenafil (0.44+/-0.06; P<0.01) and TA250 (0.45+/-0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7+/-18.4 vs 18.8+/-1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4+/-14.1 vs 117.4+/-26.9U/mg protein; P<0.001) and catalase (0.30+/-0.05 vs 0.75+/-0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil. CONCLUSIONS: Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening. PMID- 27401290 TI - Wenshen Xiaozheng Tang induces apoptosis and inhibits migration of ectopic endometriotic stromal cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Wenshen Xiaozheng Tang (WXT), a traditional Chinese medicine prescription, exerted a good therapeutic effect on endometriosis. However, the underlying mechanism is unclear. In the present study, we sought to evaluate the effect of WXT on the proliferation and migration of ectopic endometriotic stromal cells and explore the potential molecular mechanism. MATERIALS AND METHODS: Primary stromal cells derived from ectopic endometriotic lesions of patients with endometriosis were isolated and cultured. The inhibition effect of WXT on cell proliferation was determined by MTT. Apoptosis of ectopic endometriotic cells treated with WXT was analyzed with Annexin V-FITC/7-AAD staining. The activation of caspases was detected by western blot analysis. The influence of WXT on migration of ectopic endometriotic cells was measured by scratch wound healing assay and Transwell assay. The DNA binding activity of NF-kappaB and the expression of nuclear p65 protein were determined by electrophoretic mobility shift assay and western blot analysis, respectively. The impact of WXT on the expression of NF-kappaB regulated gene products involved in apoptosis and migration was determined by western blot analysis. RESULTS: WXT inhibited the proliferation of ectopic endometriotic cells in a time- and dose dependent manner. In addition, WXT treatment resulted in significant induction of apoptosis through the activation of caspases and inhibition of migration in ectopic endometriotic cells. WXT notably suppressed constitutive NF-kappaB-DNA binding activity as well as TNF-alpha induced nuclear translocation of NF-kappaB p65 subunit in ectopic endometriotic cells. Moreover, WXT diminished the expression of NF-kappaB regulated gene products involved in apoptosis and migration, including c-IAP1, c-IAP2, XIAP, survivin, Mcl-1, COX-2 and MMP-9. CONCLUSIONS: Our results indicate that WXT induces apoptosis and inhibits migration of ectopic endometriotic stromal cells. PMID- 27401291 TI - Andrographis paniculata extract attenuates pathological cardiac hypertrophy and apoptosis in high-fat diet fed mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (Burm. f.) Nees (Acanthaceae) has a considerable medicinal reputation in most parts of Asia as a potent medicine in the treatment of Endocrine disorders, inflammation and hypertension. AIM OF THE STUDY: Water extract of A. paniculata and its active constituent andrographolide are known to possess anti-inflammatory and anti apoptotic effects. Our aim is to identify whether A. paniculata extract could protect myocardial damage in high-fat diet induced obese mice. MATERIALS AND METHODS: The test mice were divided into three groups fed either with normal chow or with high fat diet (obese) or with high fat diet treated with A. paniculata extract (2g/kg/day, through gavage, for a week). RESULTS: We found that the myocardial inflammation pathway related proteins were increased in the obese mouse which potentially contributes to cardiac hypertrophy and myocardial apoptosis. But feeding with A. paniculata extract showed significant inhibition on the effects of high fat diet. CONCLUSION: Our study strongly suggests that supplementation of A. paniculata extract can be used for prevention and treatment of cardiovascular disease in obese patients. PMID- 27401292 TI - Dual effect of WIN-34B on osteogenesis and osteoclastogenesis in cytokine-induced mesenchymal stem cells and bone marrow cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: As an n-butanol fractionated extracted mixture of Lonicera japonica Thunb, dried flowers and Anemarrhena asphodeloides Bunge, root, WIN-34B has been reported the analgesic, anti-inflammatory, cartilage-repairing and protective effects in previous studies. AIM OF THE STUDY: To investigate the effect of WIN-34B on osteogenesis and osteoclastogenesis in cytokine-induced mesenchymal stem cells and bone marrow cells. MATERIALS AND METHODS: To examine the effect of WIN-34B on osteogenic differentiation, human mesenchymal stem cells (hMSCs) were treated with WIN-34B (1MUg/mL and 10MUg/mL). Alkaline phosphatase (ALP) activity was evaluated and Von Kossa staining was conducted. Mice bone marrow macrophages (BMMs) were obtained and treated with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony stimulating factor (m CSF) to induce osteoclastogenesis. To investigate osteoclast differentiation, tartrate-resistant acid phosphatase (TRAP) staining was conducted after treatment with WIN-34B. Osteoclastogenic conditions were induced by stimulating the cells with interleukin (IL)-1alpha, IL-17, and tumor necrosis factor (TNF-alpha) in hMSCs and BMMs co-culture systems. The expression levels of osteoprotegerin (OPG), RANKL, runt-related transcription factor 2 (RUNX2), IL-17, c-Fos, TNF alpha, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were measured by reverse transcription polymerase chain reaction (RT-PCR). The expression levels of nuclear factor-kappaB (NF-kappaB), inhibitory kappa B-alpha (IkappaBalpha), phospho-NF-kappaB, phospho-IkappaBalpha, beta-actin, p38 MAPK, phospho-c-Jun N terminal kinase (JNK), phospho-extracellular-signal regulated kinase (ERK), phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, and phospho-ERK were measured by western blot analysis. RESULTS: WIN-34B promoted ALP activity and mineralization of hMSCs. In TRAP-stained BMMs, the number of multinucleated cells decreased after WIN-34B treatment. WIN-34B increased the OPG/RANKL ratio and the expression of RUNX2, and suppressed the expression of IL-17, c-Fos, and TNF-alpha. It also suppressed the activation of NF-kappaB, IkappaBalpha, p38 MAPK, and JNK in a dose-dependent manner. CONCLUSIONS: These results demonstrated that WIN-34B increased osteogenesis and decreased osteoclastogenesis in cytokine induced mesenchymal stem cells and bone marrow cells via inhibition of the NF kappaB, JNK, and p38 MAPK pathways. PMID- 27401294 TI - Optical coherence tomography imaging during endovascular treatment of a patient with Takayasu arteritis. PMID- 27401293 TI - Mahuang-Xixin-Fuzi decoction reduces the infection of influenza A virus in Kidney Yang deficiency syndrome mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mahuang-Xixin-Fuzi Decoction (MXF) as a famous formula for the treatment of colds, fever, nasal congestion and headache with elder people, has always been widely used in traditional Chinese medicine. The present study is aimed at investigating the treatment effect of MXF on Kidney Yang deficiency syndrome in mice simultaneously infected with H1N1 virus. MATERIALS AND METHODS: We employed the Kidney-Yang deficiency mouse model to investigate the effect of MXF against influenza A virus (A/FM/1/47, H1N1). Mice were infected with the virus after fifteen days Kidney-Yang deficiency syndrome was established (intraperitoneal injection of estradiol benzoate), while MXF was orally administrated with 1.2-4.7g/kg/d for 6 consecutive days after inoculation. Body weight, rectal temperature, morbidity, and mortality were recorded daily. Histopathologic changes, antioxidant activity of SOD and MDA were detected. Moreover, levels of inflammatory cytokines including IL-6, IL-10, MCP-1, TNF alpha were measured in the sera of mice. RESULTS: We found that the extract of MXF at dosages of 2.3-4.7g/kg could effectively diminish mortality rate, ameliorate lung edema and inflammation. Administration of MXF decoction significantly depressed the expression of IL-6, MCP-1 and TNF-alpha, and markedly increased expression of IL-10 in serum. Simultaneously, the extract was also found to reduce MDA and increase SOD in the lung tissue of mice. CONCLUSION: These data support the notion that the extract of MXF could treat Kidney-Yang deficiency syndrome in mice simultaneously infected with influenza A virus by reducing inflammation and increasing antioxidant activities. PMID- 27401295 TI - Bulge of left atrial roof imaged by three-dimensional transoesophageal echocardiography: a novel feature of periannular abscess formation in aortic prosthesis endocarditis? PMID- 27401296 TI - Identifying culprit lesions in non-ST-elevation myocardial infarction: are new diagnostic tools always better? PMID- 27401297 TI - Endocardial radiofrequency ablation for septal hypertrophy. PMID- 27401298 TI - Who could benefit most from treatment of acute pulmonary embolism with rivaroxaban? Commentary to the article: "Acute pulmonary embolism treatment with rivaroxaban results in a shorter duration of hospitalisation compared to standard therapy.... PMID- 27401299 TI - Response to the letter concerning the article "Acute pulmonary embolism treatment with rivaroxaban results in a shorter duration of hospitalisation compared to standard therapy.... PMID- 27401300 TI - Editorial. PMID- 27401301 TI - Effect of co-administration of Hypoxis hemerocallidea extract and antiretroviral therapy (HAART) on the histomorphology and seminal parameters in Sprague Dawley rats. AB - Although the successful introduction and rollout of antiretroviral therapy has impacted positively on morbidity and mortality of HIV-positive patients, its interaction with plant-based adjuvants remain sparsely investigated. We report the interaction and effects of adjuvant treatment with highly active antiretroviral therapy (HAART) and Hypoxis hemeocallidea (HH) extracts on testicular structure of rats. A total of 63 pathogen-free adult male Sprague Dawley rats were divided into nine groups and treated according to protocols. HAART cocktail predisposed to significant negative testicular parameters of sperm count, motility and seminiferous tubular epithelial height (quantitatively) (p < .03) and also altered the histomorphology of tubules with diffuse hypoplasia in seminiferous tubules. The higher dose of HH showed a better ability to mitigate the altered parameters and compares favourably with vitamin C in this protocol. While HH did not show any deleterious impact on morphometric data, its role as adjuvant did not significantly reduce the negative impact of HAART on morphometric indices especially with the lower dosage. Further investigations are warranted on the interactions between HAART and Hypoxis. PMID- 27401302 TI - Base-Excision-Repair-Induced Construction of a Single Quantum-Dot-Based Sensor for Sensitive Detection of DNA Glycosylase Activity. AB - DNA glycosylase is an initiating enzyme of cellular base excision repair pathway which is responsible for the repair of various DNA lesions and the maintenance of genomic stability, and the dysregulation of DNA glycosylase activity is associated with a variety of human pathology. Accurate detection of DNA glycosylase activity is critical to both clinical diagnosis and therapeutics, but conventional methods for the DNA glycosylase assay are usually time-consuming with poor sensitivity. Here, we demonstrate the base-excision-repair-induced construction of a single quantum dot (QD)-based sensor for highly sensitive measurement of DNA glycosylase activity. We use human 8-oxoguanine-DNA glycosylase 1 (hOGG1), which is responsible for specifically repairing the damaged 8-hydroxyguanine (8-oxoG, one of the most abundant and widely studied DNA damage products), as a model DNA glycosylase. In the presence of biotin-labeled DNA substrate, the hOGG1 may catalyze the removal of 8-oxo G from 8-oxoG.C base pairs to generate an apurinic/apyrimidinic (AP) site. With the assistance of apurinic/apyrimidinic endonuclease (APE1), the cleavage of the AP site results in the generation of a single-nucleotide gap. Subsequently, DNA polymerase beta incorporates a Cy5-labeled dGTP into the DNA substrate to fill the gap. With the addition of streptavidin-coated QDs, a QD-DNA-Cy5 nanostructure is formed via specific biotin-streptavidin binding, inducing the occurrence of fluorescence resonance energy transfer (FRET) from the QD to Cy5. The resulting Cy5 signal can be simply monitored by total internal reflection fluorescence (TIRF) imaging. The proposed method enables highly sensitive measurement of hOGG1 activity with a detection limit of 1.8 * 10(-6) U/MUL. Moreover, it can be used to measure the enzyme kinetic parameters and detect the hOGG1 activity in crude cell extracts, offering a powerful tool for biomedical research and clinical diagnosis. PMID- 27401303 TI - Prognostic impact of p15 gene aberrations in acute leukemia. AB - The p15 gene (also known as CDKN2B, INK4B, p15INK4B), located in band 9p21, encodes a protein that induces a G1-phase cell cycle arrest through inhibition of CDK4/6 (cyclin-dependent kinase 4/6). It also plays an important role in the regulation of cellular commitment of hematopoietic progenitor cells and myeloid cell differentiation. p15 can be silenced by several mechanisms, including deletion and hypermethylation of its promoter. Homozygous p15 deletion is rare in acute myeloblastic leukemia (AML) and myelodysplastic syndromes (MDS) but frequent in acute lymphoblastic leukemia (ALL). On the contrary, methylation of the p15 promoter is identified in some 50% of the patients with AML and MDS, but is less frequent in ALL. The analysis of the 28 studies available in the literature revealed conflicting results (unfavorable, favorable or no impact) that can be due, at least in part, to methodological and/or biological pitfalls. Among those, are the heterogeneity of the methylation patterns of the p15 gene and the lack of a comprehensive analysis including transcriptional and translational inactivation that have major impact on its expression. Therefore, detection of the p15 mRNA expression (quantitative or not) may represent a more appropriate method to determine the prognostic impact of the p15 gene. PMID- 27401304 TI - Gendered Authorship and Demographic Research: An Analysis of 50 Years of Demography. AB - Demography, the official journal of the Population Association of America, has been given the highest rating among demographic journals by the Social Sciences Citation Index (SSCI). Our aim here is to investigate the development of research subfields and female authorship in Demography over the last 50 years. We find that female authorship in Demography has risen considerably since the 1980s and that currently a woman is about as likely as a man to be the sole or the first author of a paper published in the journal. However, we find some differences by subfield. Women seem to be overrepresented in the "family and household" research subfield but underrepresented in the "mortality and health" and "data and methods" categories. PMID- 27401306 TI - Letters to the Editor. PMID- 27401305 TI - Fast-track surgery improves postoperative clinical recovery and cellular and humoral immunity after esophagectomy for esophageal cancer. AB - BACKGROUND: Our aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients. METHODS: Between October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study. The patients were randomized into two groups: FTS pathway group and conventional pathway group. The postoperative hospital stay, hospitalization expenditure, and postoperative complications were recorded. The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups. RESULTS: In all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group. We found implementation of FTS pathway decreases postoperative length of stay and hospital charges (P < 0.05). In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 (P < 0.05). On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P < 0.05). However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups. CONCLUSIONS: FTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer. TRIAL REGISTRATION: ChiCTR-TRC-13003562 , the date of registration: August 29, 2013. PMID- 27401307 TI - Letters to the Editor. PMID- 27401308 TI - Influence of cigarette smoking on airway inflammation and inhaled corticosteroid treatment in patients with asthma. AB - BACKGROUND: Cigarette smoking induces neutrophilic airway inflammation and relative resistance to inhaled corticosteroids (ICS). OBJECTIVE: We evaluated the influence of cigarette smoking on airway inflammation in patients with asthma and also compared the effect of ICS between smoking and nonsmoking in patients with asthma. METHODS: Smokers with asthma (n = 81) and nonsmokers with asthma (n = 52) were recruited for the study. We examined lung function, fractional exhaled nitric oxide (FeNO) concentration, induced sputum, and acetylcholine inhalation before and 6 months after inhaling budesonide at 800 MUg/day. Thirty-four healthy volunteers were included as controls. RESULTS: Smokers with asthma showed a lower forced expiratory volume in 1 second (FEV1) to forced volume capacity (FVC) ratio (p < 0.05), a lower FeNO (p < 0.01), a lower eosinophil proportion (p < 0.05), and a higher neutrophil proportion (p < 0.05) in induced sputum than nonsmokers with asthma. Bronchial hyperresponsiveness (the provocative concentration of acetylcholine [Ach] that produced a 20% fall in FEV1 [PC20-Ach]) was increased in smokers with asthma compared with nonsmokers with asthma (p < 0.05). Both smokers with asthma and nonsmokers with asthma exhibited more prominent airway obstruction, a higher FeNO, and a higher percentage of sputum eosinophils than the controls (p < 0.05 to p < 0.001, each). After 6 months of treatment with inhaled budesonide at 800 MUg/day, the improvement in lung function (FEV1 to FVC ratio, flow at 50% forced vital capacity [V50% predicted] and flow at 25% forced vital capacity [V25% predicted]), the eosinophil proportion in induced sputum and PC20-Ach were lower in smokers with asthma than nonsmokers with asthma (p < 0.05). CONCLUSION: Smokers with asthma showed neutrophilic airway inflammation in addition to eosinophilic inflammation, and cigarette smoking impaired the efficacy of ICS treatment in mild-to-moderate asthma. These findings have important implications for the management of patients with asthma and who smoke. PMID- 27401309 TI - The effect of allergen-specific immunotherapy on offspring. AB - BACKGROUND: The incidence of allergic diseases has increased worldwide. Thus, there is a need for effective primary prevention of allergies. OBJECTIVE: The aim of the present study was to examine how allergen-specific immunotherapy (ASIT) affects the development of allergies in the generation of children whose parents were subjected to this method of treatment. METHODS: A total of 194 children with at least one parent with allergy subjected to ASIT were enrolled. These patients were compared with control individuals without ASIT. Their risk of allergy, based on medical history, examination, allergy skin-prick tests, serum total immunoglobulin E and specific immunoglobulin E concentrations was assessed. RESULTS: The children of parents subjected to immunotherapy showed significantly reduced clinical symptoms of allergic disease. The odds ratios (OR) of any allergic disease and asthma were significantly lower in children with one or both parents with allergy after ASIT compared with the children with parents with allergy and without ASIT: OR 0.73 (95% confidence interval [CI], 0.59-0.86) versus OR 1.85 (95% CI, 1.73-2.2) for any allergic disease and OR 0.63 (95% CI, 0.53-0.79) versus OR 1.36 (95% CI, 1.22-1.67) for asthma. CONCLUSION: The phenomenon of reducing the risk of allergies in children whose parents were desensitized might be important in the primary prevention of allergies. PMID- 27401310 TI - The association between hypovitaminosis D and pediatric allergic diseases: A Korean nationwide population-based study. AB - BACKGROUND: There is still considerable disagreement regarding the role of vitamin D in the development or exacerbation of allergic diseases. OBJECTIVE: To investigate the association between serum vitamin D levels and recent symptoms of allergic diseases in elementary schoolchildren. METHODS: A nationwide cross sectional survey was conducted in children ages 6-7 years from 45 randomly selected elementary schools. The presence of atopic dermatitis (AD) or asthma was defined as medical treatment of children for AD or asthma within 12 months of the survey. The presence of allergic rhinitis (AR) was defined as medical treatment for AR during the past 12 months and a positive skin test response. Current AD was defined as confirmed eczema on physical examination. Serum 25-hydroxyvitamin D (25[OH]D) was measured by chemiluminescent immunoassay. RESULTS: Questionnaire data and blood samples were collected from 3720 children. The overall prevalence rates of vitamin D insufficiency (20-29 ng/mL) and deficiency (<20 ng/mL) were 64.0% and 18.4%, respectively. For a 1 ng/mL decrease in 25(OH)D, the adjusted odds ratio (aOR) for AR was 1.020 (95% confidence interval [CI], 1.002-1.040) and the aOR for current AD was 1.027 (95% CI, 1.006-1.047). For each 1 ng/mL decrease in 25(OH)D, the aOR for positive skin-prick test reactivity was 1.013 (95% CI, 1.000-1.027). No significant association between vitamin D level and the prevalence of asthma was observed. CONCLUSIONS: A high prevalence of vitamin D deficiency and insufficiency was found in Korean elementary schoolchildren, and low vitamin D levels were associated with recent symptoms of AD and AR. PMID- 27401311 TI - Clinical and health promotion asthma management: an intervention for children and adolescents. AB - BACKGROUND: Asthma is the leading chronic condition among children. Given this international burden, clinicians and public health professionals applied the Expanded Chronic Care Model to address health adversities of pediatric patients with asthma. OBJECTIVE: This study examined the influence of a clinical health promotion initiative on asthma control and appropriate medication management among pediatric patients. METHODS: Patients (n = 304) were recruited and screened for participation in this study. All the patients participated in a motivational interview, received clinical care, and were monitored longitudinally. Eligible patients (n = 53) were referred to one or more intervention pathways regarding physical activity, nutrition, smoking cessation, and psychosocial wellness. A comparison group (n = 90) was eligible for an intervention but chose not to participate. This analysis focused on patients who were identified as needing a health intervention beyond asthma clinical care. RESULTS: Among patients who were invited to participate in the health promotion pathways, significant decreases in asthma exacerbation were achieved by the patients who participated in the intervention compared with those who did not participate (p = 0.018). Significant improvements in asthma exacerbation, activity limitations, and asthma control were attributed to the time in clinical care (p < 0.001). In this group, asthma control significantly improved with medication (p = 0.002), and age was associated with a significant decrease in asthma exacerbation (p = 0.011). CONCLUSIONS: This pilot study demonstrated preliminary benefits in a child asthma population. In addition, this experience addressed the chronicity of pediatric asthma through patient-centered care. PMID- 27401312 TI - Science, lifestyle, and human health: Challenging trilogy for the allergist/immunologist. PMID- 27401313 TI - Allergen immunotherapy now and in the future. AB - BACKGROUND: Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy provide effective treatment for allergic rhinitis and allergic asthma with clinical improvement following an adequate course of therapy persisting in most patients for years after treatment is discontinued. However, both require prolonged courses of therapy and many or most patients either do not begin or stop long before they have completed the prescribed course of treatment. METHODS: Based on review of the recent medical literature, the current status of SCIT and SLIT was reviewed as well as new approaches to allergy immunotherapy (AIT) that have promise to overcome the safety and inconvenience concerns of both the current approaches. RESULTS: New approaches to AIT include application of extracts to the skin with patches, injection into inguinal lymph nodes, alterations in the allergen molecules by chemical treatment or recombinant technology to make them less reactive with specific IgE, shifting the immune response by stimulation of toll-like receptors or suppression of Th2 responses, and finally by adjuvants such as probiotics and vitamin D. CONCLUSIONS: Current forms of immunotherapy require years of treatment. New approaches, although differing markedly in their approach to AIT, all offer marked reduction in the required period of treatment. Hopefully, some of these new approaches will prove safe and effective and obtain approval for general use. If approved, they should make AIT more widely utilized to the benefit of the allergic population. PMID- 27401314 TI - Electronic health records-Applications for the allergist/immunologist: All that glitters is not gold. AB - A review of existing literature on electronic health records (EHR) demonstrates the lack of a comprehensive analysis of the current status of, and impediments for, physicians, including allergists/immunologists, to adopting a fully functioning system. For physicians to logically embrace the use of EHRs, a comprehensive but straightforward presentation of this complex subject would be helpful. In fact, although there is some evaluative information regarding data derived from EHRs about asthma epidemiology and practice guidelines as well as recording adverse allergic reactions, it is impossible to find one scholarly article that evaluated the use of fully functional EHRs from the perspective of an allergist or immunologist. This analysis presents a review of the background and goals of EHRs and describes the major problems that delayed their widespread acceptance. Necessary solutions to the problems are presented in this article. The potential benefits of better EHRs could foster widespread acceptance and use of these systems. PMID- 27401315 TI - Asthma and chronic obstructive pulmonary disease inhalers: Techniques for proper use. AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) affect millions of Americans. Inhalers are necessary to manage these diseases, but physicians and patients often struggle to use them correctly. OBJECTIVE: To simplify inhaler use for patients and physicians. METHODS: This article compares the various inhalers used to treat asthma and COPD, their techniques for use, and the steps necessary to prime the inhaler if required. The authors provide a suggested standardized technique for the use of metered-dose inhalers, dry powder inhalers, and soft-mist inhalers to provide for a more universal approach for the use of these medications and summarizes how each product is to be used per the U.S. Food and Drug Administration approved package insert. RESULTS AND CONCLUSIONS: The simplified techniques proposed in this article for the use of metered-dose inhalers, dry powder inhalers, and soft mist inhalers used to treat asthma and COPD may limit inhaler misuse and aid in proper medication delivery and treatment. PMID- 27401316 TI - Efficacy and safety evaluation of once-daily fluticasone furoate/vilanterol in Asian patients with asthma uncontrolled on a low- to mid-strength inhaled corticosteroid or low-dose inhaled corticosteroid/long-acting beta2-agonist. AB - BACKGROUND: Response to inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combinations varies across ethnic groups. OBJECTIVE: To investigate the efficacy and safety of the ICS/LABA combination fluticasone furoate/vilanterol (FF/VI) 100/25 MUg in Asian patients with asthma. METHODS: A randomized (1:1), 12 week, double-blind, placebo-controlled, parallel group, multicenter phase III study of once-daily FF/VI 100/25 MUg versus placebo in patients of Asian ancestry ages >=12 years with asthma, uncontrolled on a low- to mid-strength ICS or low dose ICS/LABA. The primary end point was the mean change from baseline in the daily evening peak expiratory flow. Secondary end points were the mean change from baseline in percentage rescue-free 24-hour periods, daily morning peak expiratory flow, percentage symptom-free 24-hour periods, Asthma Quality of Life Questionnaire score, adverse events, and severe exacerbations. RESULTS: The intent-to-treat population was 307 patients. There were significant (p < 0.001) improvements from baseline for FF/VI 100/25 MUg versus placebo in evening peak expiratory flow (51.0 L/min [95% confidence interval {CI}, 42.2-59.7 L/min]) and all secondary end points (percentage rescue-free 24-hour periods 21.8% [95% CI, 14.6-29.1%]; morning peak expiratory flow 52.9 L/min [95% CI, 44.2-61.6 L/min]; percentage symptom-free 24-hour periods 15.8% [95% CI, 9.4-22.3%]; Asthma Quality of Life Questionnaire score 0.52 [95% CI, 0.28, 0.75]). On-treatment adverse events were 35% with FF/VI (n = 2 [serious]), 31% with placebo; severe exacerbations were FF/VI (n = 1), placebo (n = 7). CONCLUSIONS: In patients of Asian ancestry, once-daily FF/VI 100/25 MUg produced statistically and clinically significant improvements in efficacy end points versus placebo, with a generally similar safety profile. Results were consistent with a global phase III study of FF/VI 100/25 MUg. Clinicaltrials.gov NCT01498679. PMID- 27401317 TI - Obesity-asthma phenotype: Effect of weight gain on asthma control in adults. AB - INTRODUCTION: The obesity-asthma phenotype has become an increasingly common situation in our clinical practice. The mechanisms behind poor asthma control in subjects who are obese remain unclear. We aimed to determine the effect of obesity on asthma control in a group of adult patients Method: Subjects who had been diagnosed as having asthma and who were admitted to our clinic were included to this study. Body mass index (BMI) and asthma control status of the patients were evaluated. BMI values at the time of diagnosis were also collected from the patient files, and the difference between basal and current BMI values were calculated. The effect of obesity and weight gain on asthma control was investigated. RESULTS: The study population was composed of 218 patients (29 men, 189 women), with a mean (standard deviation) age of 52.01 +/- 11.6 years. Fifty four percent of the patients were obese, 27.5% were overweight, and 18.3% were of normal weight. The baseline and current BMI values were higher in women than in the men. BMI increased with the increase in age or disease duration. Asthma control was poor in the patients who were obese and overweight despite optimal treatment. Moreover, asthma control was worse in patients who gained weight during the follow-up period. CONCLUSION: In our study, we found a significant relationship between obesity and asthma control. In addition, weight gain and being nonatopic also was found to worsen asthma control. In light of our finding that weight gain led to a decrease in asthma control, we suggest that weight loss may improve the course of asthma. PMID- 27401318 TI - Smoking status and smoking cessation intervention among U.S. adults hospitalized for asthma exacerbation. AB - BACKGROUND: In a previous multicenter study during 1999-2000, we found a high prevalence of smoking among patients hospitalized for asthma exacerbations (35%) and suboptimal smoking cessation efforts. There have been no recent multicenter efforts to examine the smoking status and implementation of smoking cessation efforts among patients hospitalized for asthma exacerbation. OBJECTIVE: To investigate the prevalence of cigarette smoking and the proportion and characteristics of patients who received an inpatient smoking cessation intervention. METHODS: We conducted a secondary analysis of a 25-center observational study, which included 597 U.S. adults hospitalized for asthma exacerbation during 2012-2013. RESULTS: Among the analytic cohort, 215 (36%) were current smokers. In the multivariable model, compared with patients with private health insurance, those with public health insurance (odds ratio [OR] 1.71 [95% confidence interval {CI}, 1.06-2.77]) or no health insurance (OR 1.75 [95% CI, 1.02-2.99]) were more likely to be current smokers. By contrast, patients with a previous evaluation by an asthma specialist in the past 12 months (OR 0.49 [95% CI, 0.28-0.86]) and use of inhaled corticosteroids (OR 0.63 [95% CI, 0.43-0.93]) were less likely to be current smokers. Among current smokers, only 55% received smoking cessation interventions during their hospitalization. In the multivariable model, current smokers who had public health insurance (OR 0.25 [95% CI, 0.07-0.82]) or no health insurance (OR 0.26 [95% CI, 0.07-0.94]) were less likely to receive inpatient smoking cessation interventions compared with those with private health insurance. CONCLUSION: Our findings showed a persistently high prevalence of smokers among U.S. patients hospitalized for asthma exacerbations and an underutilized opportunity to provide this at-risk population with smoking cessation interventions. PMID- 27401319 TI - Effect of Lactobacillus rhamnosus GG and vitamin D supplementation on the immunologic effectiveness of grass-specific sublingual immunotherapy in children with allergy. AB - BACKGROUND: An important issue in sublingual immunotherapy (SLIT) is how to improve efficacy. OBJECTIVE: To compare the clinical and immunologic efficacy of SLIT given alone and, to enhance clinical efficacy, given with probiotic or vitamin D supplementation. METHODS: One hundred children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis participated in a 5-month prospective, randomized, double-blind, placebo-controlled trial. Children received 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation, probiotic, or placebo. The control group included children with allergy who did not qualify for immunotherapy. Primary end points included a symptom-medication score, lung function, and exhaled nitric oxide concentration. The secondary end point was the immunologic efficacy measured by the following: CD4(+)CD25(+)Foxp3(+) (forkhead box P3) cells, Toll-like receptor (TLR) 4, interleukin (IL) 1, IL-6, tumor necrosis factor, IL-10, and transforming growth factor beta-1 levels in cell culture supernatants. RESULTS: Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group. In the SLIT-probiotic group, between-group analysis showed significantly higher CD4(+)CD25(+)Foxp3(+) induction compared with the SLIT group and higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1). An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR positive cells recruitment and an increase in transforming growth factor beta-1 production were independently associated with a better clinical effect of SLIT in children. CONCLUSIONS: We demonstrated the clinical and immunologic effect of probiotic and vitamin D supplementation on SLIT. Probiotic supplementation showed better clinical and immunologic response in children with allergic rhinitis. PMID- 27401320 TI - Serum clusterin level in children with atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a marker to assess inflammatory diseases. The clusterin levels in AD have not been evaluated thus far. OBJECTIVE: We evaluated serum clusterin levels in children with AD and assessed the relationship between serum clusterin levels and the severity of AD. METHOD: The study enrolled a total 140 children, of whom 100 had AD (n = 100) and 40 were healthy (n = 40). The severity of AD was scored by using the SCORing Atopic Dermatitis (SCORAD). Total serum immunoglobulin E and specific immunoglobulin E levels against egg whites, cow's milk, peanuts, soybeans, wheat, and Dermatophagoides farinae were measured. Clusterin levels in serum were measured by enzyme-linked immunosorbent assay. RESULTS: The mean (interquartile range) age of the children was 5.1 years (1.3-8.4 years), and 92 (69.3%) of the children were boys. The mean (standard deviation) SCORAD index was 50.4 +/- 17. The mean (standard deviation) clusterin level of children with AD was higher than that in the healthy control group children (148.13 +/- 4.3 pg/mL versus 144.85 +/- 5.1 pg/mL; p = 0.001). Serum clusterin levels were correlated with the SCORAD index (r = 0.327, p = 0.002). CONCLUSIONS: The serum clusterin level was higher in children with AD than in the healthy control group and increased with the severity of AD. Serum clusterin may be a candidate molecule that reflects AD and its severity. PMID- 27401321 TI - A 47-year-old man with tongue swelling. AB - Intermittent tongue angioedema can be the initial presentation of several disorders including angiotensin-converting-enzyme inhibitor induced angioedema and hereditary angioedema. Persistent angioedema on the other hand, can be associated with amyloidosis, tumors, thyroid disorders and acromegaly. We present a case of intermittent episodes of tongue swelling progressing to macroglossia. PMID- 27401322 TI - For the Patient. PMID- 27401324 TI - Slow response contributed to scale of west African Ebola epidemic, CDC concludes. PMID- 27401325 TI - Renal cell carcinoma. PMID- 27401323 TI - The effect of ultrasound with acoustic radiation force on rabbit lung tissue: a preliminary study. AB - PURPOSE: Acoustic radiation force (ARF) elastography has recently become available. The previous animal studies have revealed lung injuries induced by diagnostic ultrasound, but the effects on the lung resulting from exposure to ultrasound with ARF are unknown. This study aimed to assess the risk of lung injury associated with ultrasound with ARF. METHODS: A focused 2.5-MHz transducer that emits ultrasound with ARF was used. A rabbit was anesthetized, and the transducer was placed in the right subcostal region. Exposure settings of mechanical index (MI) 0.80, pulse duration 10 ms, pulse repetition time 5 s, and exposure time 150 s were applied. RESULTS: One red spot (7 * 6 mm) was observed on the surface of the right lung corresponding to the area of exposure. Alveolar hemorrhage was observed microscopically. This lesion was visible across a range of 20-170 MUm in depth from the pleural surface. CONCLUSION: The first example of lung hemorrhage induced by ultrasound with ARF was observed in this study. This observation suggests the possibility of lung injury in humans when ARF elastography is applied with the transducer directed toward the lung. Further studies are needed to determine the safety of this modality. PMID- 27401326 TI - Total minimally invasive esophagectomy for esophageal cancer: approaches and outcomes. AB - Since the introduction of minimally invasive esophagectomy 25 years ago, its use has been reported in several high volume centers. With only one published randomized control trial and five meta-analyses comparing its outcomes to open esophagectomy, available level I evidence is very limited. Available technical approaches include total minimally invasive transthoracic (Ivor Lewis or McKeown) or transhiatal esophagectomy; several hybrid options are available with one portion of the procedure completed via an open approach. A review of available level I evidence with focus on total minimally invasive esophagectomy is presented. The old debate regarding the superiority of a transthoracic versus transhiatal approach to esophagectomy may have been settled by minimally invasive esophagectomy as only few centers are reporting on the latter being utilized. The studies with the highest level of evidence available currently show that minimally invasive techniques via a transthoracic approach are associated with less overall morbidity, fewer pulmonary complications, and shorter hospital stays than open esophagectomy. There appears to be no detrimental effect on oncologic outcomes and possibly an added benefit derived by improved lymph node retrieval. Quality of life improvements may also translate into improved survival, but no conclusive evidence exists to support this claim. Robotic and hybrid techniques have also been implemented, but there currently is no evidence showing that these are superior to other minimally invasive techniques. PMID- 27401327 TI - Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications. AB - To optimally exploit the potential of (tumor-) targeted nanomedicines, platform technologies are needed in which physicochemical and pharmaceutical properties can be tailored according to specific medical needs and applications. We here systematically customized the properties of core-crosslinked polymeric micelles (CCPM). The micelles were based on mPEG-b-pHPMAmLacn (i.e. methoxy poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate]), similar to the block copolymer composition employed in CriPec(r) docetaxel, which is currently in phase I clinical trials. The CCPM platform was tailored with regard to size (30 to 100nm), nanocarrier degradation (1month to 1year) and drug release kinetics (10 to 90% in 1week). This was achieved by modulating the molecular weight of the block copolymer, the type and density of the crosslinking agent, and the hydrolytic sensitivity of the drug linkage, respectively. The high flexibility of CCPM facilitates the development of nanomedicinal products for specific therapeutic applications. PMID- 27401328 TI - Preventing violence-related injuries in England and Wales: a panel study examining the impact of on-trade and off-trade alcohol prices. AB - OBJECTIVE: To examine the influence of real on-trade and off-trade alcohol prices and socioeconomic and environmental factors on rates of violence-related emergency department (ED) attendances in England and Wales over an 8-year period. METHODS: Anonymised injury data which included attendance date, age and gender of patients aged over 18 years who reported injury in violence were collected from a structured sample of 100 EDs across England and Wales between 1 January 2005 and 31 December 2012. Alcohol prices and socioeconomic measures were obtained from the UK Office for National Statistics. Panel techniques were used to derive a statistical model. RESULTS: Real on-trade (beta=-0.661, p<0.01) and off-trade (beta=-0.277, p<0.05) alcohol prices were negatively related with rates of violence-related ED attendance among the adult population of England and Wales, after accounting for the effects of regional poverty, income inequality, youth spending power and seasonal effects. It is estimated that over 6000 fewer violence-related ED attendances per year in England and Wales would result from a 1% increase in both on-trade and off-trade alcohol prices above inflation. Of the variables studied, changes in regional poverty and income inequality had the greatest effect on violence-related ED attendances in England and Wales. CONCLUSIONS: Small increases in the price of alcohol, above inflation, in both markets, would substantially reduce the number of patients attending EDs for treatment of violence-related injuries in England and Wales. Reforming the current alcohol taxation system may be more effective at reducing violence related injury than minimum unit pricing. PMID- 27401329 TI - Non-invasive ventilation for COPD exacerbations in a non-ICU setting. PMID- 27401330 TI - Which method is best for an early accurate diagnosis of acute heart failure? Comparison between lung ultrasound, chest X-ray and NT pro-BNP performance: a prospective study. AB - Acute heart failure is a common condition among adults presenting with dyspnea in the Emergency Department (ED), still the diagnosis is challenging as objective standardized criteria are lacking. First line work-up, other then clinical findings, is nowadays made with lung ultrasound imaging study, chest X-ray study and brain natriuretic peptide (BNP) level determination; however, it is not clear which is the best diagnostic test to be used and whether there is any real benefit for clinical judgement. We set up this study to compare the performances of these three diagnostic tools; furthermore, we combined them to find the best possible approach to dyspneic patients. This is a prospective observational study based in the ED. We enrolled adults presenting with dyspnea not trauma-related, they underwent lung ultrasound, and chest X-ray studies, and NT pro-BNP level determination. Then we compared the results with the diagnosis of acute heart failure established by an independent panel of experts. 236 patients were enrolled in the study. We find sensitivity and specificity for lung ultrasound of 57.73 and 87.97 %, for chest X-ray 74.49 and 86.26 %, for NT pro-BNP 97.59 and 27.56 %, respectively. Combining together the chest X-ray and lung ultrasound, we find the best overall performance with 84.69 % sensitivity, 77.69 % specificity and 87.07 % negative predictive value. From our results, we could not identify the "best test" to diagnose acute heart failure in an emergency setting, although we could suggest that a stepwise workup combining chest X-ray and lung ultrasound at first, then for those negative, a determination of NT pro-BNP assay would be a reasonable approach to the dyspneic patient. PMID- 27401331 TI - Depressive symptoms, functional measures and long-term outcomes of high-risk ST elevated myocardial infarction patients treated by primary angioplasty. AB - The presence of major depressive symptoms is usually considered a negative long term prognostic factor after an acute myocardial infarction (AMI); however, most of the supporting research was conducted before the era of immediate reperfusion by percutaneous coronary intervention. The aims of this study are to evaluate if depression still retains long-term prognostic significance in our era of immediate coronary reperfusion, and to study possible correlations with clinical parameters of physical performance. In 184 patients with recent ST-elevated AMI (STEMI), treated by immediate reperfusion, moderate or severe depressive symptoms (evaluated by Beck Depression Inventory version I) were present in 10 % of cases. Physical performance was evaluated by two 6-min walk tests and by a symptom limited cardiopulmonary exercise test: somatic/affective (but not cognitive/affective) symptoms of depression and perceived quality of life (evaluated by the EuroQoL questionnaire) are worse in patients with lower levels of physical performance. Follow-up was performed after a median of 29 months by means of telephone interviews; 32 major adverse cardiovascular events (MACE) occurred. The presence of three vessels disease and low left ventricle ejection fraction are correlated with a greater incidence of MACE; only somatic/affective (but not cognitive/affective) symptoms of depression correlate with long-term outcomes. In patients with recent STEMI treated by immediate reperfusion, somatic/affective but not cognitive/affective symptoms of depression show prognostic value on long-term MACE. Depression symptoms are not predictors "per se" of adverse prognosis, but seem to express an underlying worse cardiac efficiency, clinically reflected by poorer physical performance. PMID- 27401332 TI - Risk factors for an acute exacerbation of idiopathic pulmonary fibrosis. AB - BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis are major causes of morbidity and mortality among patients with idiopathic pulmonary fibrosis. However, acute exacerbations remain unpredictable. The aim of this study was to investigate risk factors for acute exacerbations of idiopathic pulmonary fibrosis. METHODS: We performed a retrospective cohort study of patients with idiopathic pulmonary fibrosis who visited our institutions from January 1999 to September 2014. We investigated risk factors for acute exacerbations in patients with idiopathic pulmonary fibrosis diagnosed retrospectively based on the official 2011 idiopathic pulmonary fibrosis ATS/ERS/JRS/ALAT Update Statement. RESULTS: The idiopathic pulmonary fibrosis study cohort included 65 subjects. The median follow-up period was 2.6 years. During follow-up, 24 patients (36.9 %) experienced acute exacerbations. A Kaplan-Meier curve demonstrated that the 1 year, 2-year, and 3-year incidences of acute exacerbation were 9.6, 19.2 and 31.0 %, respectively. Acute exacerbation exerted a significant impact on overall survival among those with the disease. A log-rank test showed that baseline cardiovascular diseases, higher GAP (gender, age, physiology) stage (>=II), higher serum lactate dehydrogenase level (>=180 U/L), higher serum surfactant protein-D level (>=194.7 ng/mL), higher neutrophil (>=1.77 %) and eosinophil (>=3.21 %) percentages in bronchoalveolar lavage fluid samples, and treatment with an immunosuppressive agent after diagnosis were associated with poor acute exacerbation-free probability. In the Cox analysis adjusted for treatment with an immunosuppressive agent, baseline cardiovascular diseases, higher GAP stage (>=II), and higher eosinophil percentage (>=3.21 %) in bronchoalveolar lavage fluid samples were predictors of an acute exacerbation of idiopathic pulmonary fibrosis. CONCLUSIONS: This study demonstrated that baseline cardiovascular diseases, higher GAP stage (>=II), and higher eosinophil percentage (>=3.21 %) in bronchoalveolar lavage fluid samples were associated with the onset of an acute exacerbation of idiopathic pulmonary fibrosis. PMID- 27401333 TI - Near-Infrared Spectroscopy Assay of Key Quality-Indicative Ingredients of Tongkang Tablets. AB - The objective of this paper is to develop an easy and fast near-infrared spectroscopy (NIRS) assay for the four key quality-indicative active ingredients of Tongkang tablets by comparing the true content of the active ingredients measured by high performance liquid chromatography (HPLC) and the NIRS data. The HPLC values for the active ingredients content of Cimicifuga glycoside, calycosin glucoside, 5-O-methylvisamminol and hesperidin in Tongkang tablets were set as reference values. The NIRS raw spectra of Tongkang tablets were processed using first-order convolution method. The iterative optimization method was chosen to optimize the band for Cimicifuga glycoside and 5-O-methylvisamminol, and correlation coefficient method was used to determine the optimal band of calycosin glucoside and hesperidin. A near-infrared quantitative calibration model was established for each quality-indicative ingredient by partial least squares method on the basis of the contents detected by HPLC and the obtained NIRS spectra. The correlation coefficient R 2 values of the four models of Cimicifuga glycoside, calycosin glucoside, 5-O-methylvisamminol and hesperidin were 0.9025, 0.8582, 0.9250, and 0.9325, respectively. It was demonstrated that the accuracy of the validation values was approximately 90% by comparison of the predicted results from NIRS models and the HPLC true values, which suggested that NIRS assay was successfully established and validated. It was expected that the quantitative analysis models of the four indicative ingredients could be used to rapidly perform quality control in industrial production of Tongkang tablets. PMID- 27401334 TI - Preparation and Optimization of Immediate Release/Sustained Release Bilayered Tablets of Loxoprofen Using Box-Behnken Design. AB - The aim of our current study was to characterize and optimize loxoprofen immediate release (IR)/sustained release (SR) tablet utilizing a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors included ratio of drug in the IR layer to total drug (X 1), ratio of HPMC to drug in the SR layer (X 2), and ratio of Eudragit RL PO to drug in the SR layer (X 3). The dependent variables assessed were % drug released in distilled water at 30 min (Y 1), % drug released in pH 1.2 at 2 h (Y 2), and % drug released in pH 6.8 at 12 h (Y 3). The responses were fitted to suitable models and statistical validation was performed using analysis of variance. In addition, response surface graphs and contour plots were constructed to determine the effects of different factor level combinations on the responses. The optimized loxoprofen IR/SR tablets were successfully prepared with the determined amounts of ingredients that showed close agreement in the predicted and experimental values of tablet characterization and drug dissolution profile. Therefore, BBD can be utilized for successful optimization of loxoprofen IR/SR tablet, which can be regarded as a suitable substitute for the current marketed formulations. PMID- 27401335 TI - Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. AB - Histological regression in primary cutaneous melanoma occurs in 10-35% of cases. Although a large body of literature exists to suggest that histological regression serves very little purpose in predicting biologic behaviour with melanoma, recognizing the presence of regression at clinical and histological ground may still retain some value in grading melanoma aggressiveness. In the current review, a comprehensive overview of the main aspects of regression will be provided. Histologically, many classifications have been reported so far, but all of them only agreed on the presence of an infiltrate of lymphocytes admixed with pigment-laden macrophages underlying an atrophic epidermis with flattened rete ridges. Upon dermoscopy, regression is also named Blue White Scar-like areas and could be variably admixed with granularity or peppering. Almost fully regressed lesions represent a main diagnostic issue in dermoscopy, and thus, confocal microscopy can be of help to identify whether the tumour is melanocytic or not. The clinical utility of regression as a prognostic factor has been challenged recently. Nowadays, evidences showed that it is less likely associated to SLN metastases. PMID- 27401336 TI - Fronto-limbic engagement during moral processing in stimulant users. PMID- 27401337 TI - Abnormal fronto-limbic engagement in incarcerated stimulant users during moral processing. AB - RATIONALE: Stimulant use is a significant and prevalent problem, particularly in criminal populations. Previous studies found that cocaine and methamphetamine use is related to impairment in identifying emotions and empathy. Stimulant users also have abnormal neural structure and function of the ventromedial prefrontal cortex (vmPFC), amygdala, and anterior (ACC) and posterior cingulate (PCC), regions implicated in moral decision-making. However, no research has studied the neural correlates of stimulant use and explicit moral processing in an incarcerated population. OBJECTIVES: Here, we examine how stimulant use affects sociomoral processing that might contribute to antisocial behavior. We predicted that vmPFC, amygdala, PCC, and ACC would show abnormal neural response during a moral processing task in incarcerated methamphetamine and cocaine users. METHODS: Incarcerated adult males (N = 211) were scanned with a mobile MRI system while completing a moral decision-making task. Lifetime drug use was assessed. Neural responses during moral processing were compared between users and non-users. The relationship between duration of use and neural function was also examined. RESULTS: Incarcerated stimulant users showed less amygdala engagement than non users during moral processing. Duration of stimulant use was negatively associated with activity in ACC and positively associated with vmPFC response during moral processing. CONCLUSIONS: These results suggest a dynamic pattern of fronto-limbic moral processing related to stimulant use with deficits in both central motive and cognitive integration elements of biological moral processes theory. This increases our understanding of how drug use relates to moral processing in the brain in an ultra-high-risk population. PMID- 27401338 TI - Application of Glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia. AB - BACKGROUND: We investigated the effects of glutamine (Gln)-enriched nutritional therapy during chemotherapy on the nutritional status and immune function of children with acute lymphoblastic leukemia (ALL). METHODS: We enrolled 48 children who were newly diagnosed with ALL in our department during the period of 2013.1-2014.12. The patients (follow random number table) were randomly divided into the control group (peptamen) and the treatment group (peptamen + glutamine), 24 cases in each group. The remission induction regimens were all based on VDLP (D) chemotherapy (VCR (Vincrisstine), DNR (Daunomycin), L-ASP (L-Asparagiase), Prednisolone and Dexamethasone). The treatment group received Gln-enriched nutritional therapy every day during the full course of chemotherapy,and the control group is as same as the treatment group except without glutamine. The indicators of general nutritional status, such as weight, height, and triceps skinfold thickness, and the indicators of biochemical tests, such as serum albumin, prealbumin, creatinine-height index, retinol binding protein, and urinary hydroxyproline index, were compared between the two groups at the end of the first, second, third and the fourth week when the chemotherapy was completed. And in the fourth week, flow cytometry was applied to detect the levels of T cell subsets and the activities of natural killer (NK) cells in peripheral blood of the two groups. RESULTS: 1. after 4 weeks nutritional therapy, there is no significant difference (p > 0.05) between the two groups of children in weight, height and other indicators. 2. At the end of 2 weeks treatment, the level of prealbumin (PA) and retinol-binding protein (RBP) is higher in treatment group than that in the control group (P <0.05), at the end of 3 weeks treatment, the thickness of triceps skinfold is higher (P <0.05) than that in the control group; 3. At the end of 3 and 4 weeks, the concentrations serum ALB, PA, RBP and UHI were higher than in the control group (P <0.05); 4. There is statistically significant (p < 0.05) between the two groups in edema incidence; 5. At the end of treatment (4 weeks), the percentages of CD3 +, CD4 +, CD4 +/CD8 +, NK cell are significantly decreased in the two groups (P <0.05). CONCLUSION: Gln-enriched nutritional therapy can effectively improve the systemic nutritional status of children with leukemia, improve immune function. PMID- 27401339 TI - Hartmann's procedure vs abdominoperineal resection with intersphincteric dissection in patients with rectal cancer: a randomized multicentre trial (HAPIrect). AB - BACKGROUND: The use of Hartmann's procedure in the old and frail and/or in patients with fecal incontinence is increasing, even though some data have reported high postoperative rates of pelvic abscesses. Abdominoperineal excision with intersphincteric dissection has been proposed as a better alternative and is performed increasingly both nationally and internationally. However, no studies have been performed to support this. The aim of this study is to randomize patients between Hartmann's procedure and abdominoperineal excision with intersphincteric dissection and compare post-operative surgical morbidity and quality of life. The hypothesis is that intersphincteric abdominoperineal excision provides less pelvic and perineal morbidity. METHODS/DESIGN: In this multicentre randomized controlled study, Hartmann's procedure will be compared with intersphincteric abdominoperineal excision in patients with rectal cancer unsuitable for an anterior resection. The patients are operated in different ways around the ano-rectum, otherwise the same procedure is performed with total mesorectal excision and all will receive a colostomy. The one-month postoperative control will focus on post-operative surgical complications, especially the perineal-pelvic, reoperations and other interventions. After one year, late complications such as pain in the perineal or pelvic area or disorders such as secretion or bleeding from the anorectal stump will be recorded and a follow-up of quality of life performed. Histological and oncological data will also be recorded, the latter up to 5 years post-operatively. DISCUSSION: The HAPIrect trial is the first randomized controlled trial comparing standard low Hartmann's procedure with intersphincteric abdominoperineal excision in patients with rectal cancer with the aim of categorizing the post-operative surgical morbidity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01995396 . Date of registration November 25, 2013. PMID- 27401340 TI - Evolutionary magnetic resonance appearance of renal cell carcinoma after percutaneous cryoablation. AB - OBJECTIVE: To determine the evolutionary MRI appearance of renal cell carcinoma (RCC) following cryoablation. METHODS: For this institution review board-approved study, we recruited patients with biopsy-proven RCC and treated them with percutaneous cryoablation between November 2009 and October 2014. Two radiologists retrospectively reviewed the pre-procedural and follow-up MRI. The findings included tumour sizes, signal intensities on T1 weighted imaging (T1WI), T2 weighted imaging (T2WI), diffusion-weighted imaging, apparent diffusion coefficient (ADC) map and contrast enhancement patterns. The ADC values of the tumours before and after treatment were measured. RESULTS: A total of 26 patients were enrolled. The ablated tumours exhibited predominantly high signals on T1WI at 1-9-month follow-up (47.1% strong hyperintense at 3 months) and subsequently returned to being isointense. In T2WI, the signals of the ablated tumours were highly variable during the first 3 months and became strikingly hypointense after 6 months (58.3% strong hypointense at 6 months). Diffusion restriction was prominent during the first 3 months (lowest ADC: 0.62 +/- 0.29 * 10(-3) mm(2) s( 1) at 1 month). Contrast enhancement persisted up to 6 months after the procedure. The residual enhancement gradually increased in the dynamic scan and was most prominent in the delay phase. CONCLUSION: The MRI of the cryoablated renal tumour follows a typical evolutionary pattern. ADVANCES IN KNOWLEDGE: Familiarity of practitioners with the normal post-cryoablation change of RCC on MRI can enable the early detection and prevention of tumour recurrence. PMID- 27401341 TI - Neurobehavioral assessment following e-cigarette refill liquid exposure in adult rats. AB - The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28 MUl/kg of body weight of e-liquid with/without a dose of 0.5 mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela's inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out. PMID- 27401343 TI - Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator. AB - Medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (Aire) are critical for preventing the onset of autoimmunity. However, the differentiation program of Aire-expressing mTECs (Aire(+) mTECs) is unclear. Here, we describe novel embryonic precursors of Aire(+) mTECs. We found the candidate precursors of Aire(+) mTECs (pMECs) by monitoring the expression of receptor activator of nuclear factor-kappaB (RANK), which is required for Aire(+) mTEC differentiation. pMECs unexpectedly expressed cortical TEC molecules in addition to the mTEC markers UEA-1 ligand and RANK and differentiated into mTECs in reaggregation thymic organ culture. Introduction of pMECs in the embryonic thymus permitted long-term maintenance of Aire(+) mTECs and efficiently suppressed the onset of autoimmunity induced by Aire(+) mTEC deficiency. Mechanistically, pMECs differentiated into Aire(+) mTECs by tumor necrosis factor receptor-associated factor 6-dependent RANK signaling. Moreover, nonclassical nuclear factor-kappaB activation triggered by RANK and lymphotoxin-beta receptor signaling promoted pMEC induction from progenitors exhibiting lower RANK expression and higher CD24 expression. Thus, our findings identified two novel stages in the differentiation program of Aire(+) mTECs. PMID- 27401342 TI - Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets. AB - Naive CD4(+) T cells differentiate into specific effector subsets-Th1, Th2, Th17, and T follicular helper (Tfh)-that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4(+) T cell differentiation in vitro. IL12Rbeta1/TYK2 and IFN-gammaR/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10-secreting cells. IL12Rbeta1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4(+) T cell effector function in the settings of infection, vaccination, or immune dysregulation. PMID- 27401344 TI - Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis. AB - Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2 V617F and mutations in epigenetic regulator genes, including EZH2 In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contribute synergistically to the development of MPN. The MPN phenotype induced by JAK2 V617F was accentuated in JAK2-V617F;Ezh2(-/-) mice, resulting in very high platelet and neutrophil counts, more advanced myelofibrosis, and reduced survival. These mice also displayed expansion of the stem cell and progenitor cell compartments and a shift of differentiation toward megakaryopoiesis at the expense of erythropoiesis. Single cell limiting dilution transplantation with bone marrow from JAK2-V617F;Ezh2(+/-) mice showed increased reconstitution and MPN disease initiation potential compared with JAK2-V617F alone. RNA sequencing in Ezh2-deficient hematopoietic stem cells (HSCs) and megakaryocytic erythroid progenitors identified highly up-regulated genes, including Lin28b and Hmga2, and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) analysis of their promoters revealed decreased H3K27me3 deposition. Forced expression of Hmga2 resulted in increased chimerism and platelet counts in recipients of retrovirally transduced HSCs. JAK2-V617F-expressing mice treated with an Ezh2 inhibitor showed higher platelet counts than vehicle controls. Our data support the proposed tumor suppressor function of EZH2 in patients with MPN and call for caution when considering using Ezh2 inhibitors in MPN. PMID- 27401347 TI - Electrostatically enhanced FF interactions through hydrogen bonding, halogen bonding and metal coordination: an ab initio study. AB - In this manuscript the ability of hydrogen and halogen bonding interactions, as well as metal coordination to enhance FF interactions involving fluorine substituted aromatic rings has been studied at the RI-MP2/def2-TZVPD level of theory. We have used 4-fluoropyridine, 4-fluorobenzonitrile, 3-(4 fluorophenyl)propiolonitrile and their respective meta derivatives as aromatic compounds. In addition, we have used HF and IF as hydrogen and halogen bond donors, respectively, and Ag(i) as the coordination metal. Furthermore, we have also used HF as an electron rich fluorine donor entity, thus establishing FF interactions with the above mentioned aromatic systems. Moreover, a CSD (Cambridge Structural Database) search has been carried out and some interesting examples have been found, highlighting the impact of FF interactions involving aromatic fluorine atoms in solid state chemistry. Finally, cooperativity effects between FF interactions and both hydrogen and halogen bonding interactions have been analyzed and compared. We have also used Bader's theory of "atoms in molecules" to further describe the cooperative effects. PMID- 27401345 TI - The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor initiating cells to bromodomain inhibition. AB - EZH2 is a component of polycomb repressive complex 2 (PRC2) and functions as an H3K27 methyltransferase. Loss-of-function mutations in EZH2 are associated with poorer outcomes in patients with myeloproliferative neoplasms (MPNs), particularly those with primary myelofibrosis (MF [PMF]). To determine how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for an Ezh2 conditional deletion and activating mutation in JAK2 (JAK2V617F) present in patients with PMF. The deletion of Ezh2 in JAK2(V617F) mice markedly promoted the development of MF, indicating a tumor suppressor function for EZH2 in PMF. The loss of Ezh2 in JAK2(V617F) hematopoietic cells caused significant reductions in H3K27 trimethylation (H3K27me3) levels, resulting in an epigenetic switch to H3K27 acetylation (H3K27ac). These epigenetic switches were closely associated with the activation of PRC2 target genes including Hmga2, an oncogene implicated in the pathogenesis of PMF. The treatment of JAK2(V617F)/Ezh2-null mice with a bromodomain inhibitor significantly attenuated H3K27ac levels at the promoter regions of PRC2 targets and down-regulated their expression, leading to the abrogation of MF-initiating cells. Therefore, an EZH2 insufficiency not only cooperated with active JAK2 to induce MF, but also conferred an oncogenic addiction to the H3K27ac modification in MF-initiating cells that was capable of being restored by bromodomain inhibition. PMID- 27401348 TI - Evaluation of the quality of care of a haemodialysis public-private partnership programme for patients with end-stage renal disease. AB - BACKGROUND: Haemodialysis (HD) is one of the life-saving options for patients with end stage renal disease but demand for this treatment exceeds capacity in publicly funded hospitals. One novel approach to addressing this problem is through a shared-care model whereby government hospitals partner with qualified private HD service providers to increase the accessibility of HD for needy patients. The aim of this study is to evaluate and enhance the quality of care (QOC) provided in such a shared-care programme in Hong Kong, the Haemodialysis Public-Private Partnership Programme (HD-PPP). METHODS/DESIGN: This is a longitudinal study based on Action Learning and Audit Spiral methodologies to measure the achievement of pre-set target standards for the HD-PPP programme over three evaluation cycles. The QOC evaluation framework is comprised of structure, process and outcome criteria with target standards in each domain developed from review of the evidence and in close collaboration with the HD-PPP working group. During each evaluation cycle, coordinators of each study site complete a questionnaire to determine adherence with structural criteria of care. Process and clinical outcomes, such as adverse events and dialysis adequacy, are extracted from the patient records of consenting study participants while face-to face interviews are conducted to ascertain patient-reported outcomes such as self efficacy and health-related quality of life. DISCUSSION: The study relies on the successful implementation of partnership-based action research to develop an evidence-based and pragmatic framework for evaluation of quality of care in an iterative fashion, and to use it to identify possible areas of quality enhancements in a shared-care programme for HD patients. The approach we take in this study emphasizes partnership and engagement with the clinical and administrative programme team, a robust but flexible evaluation framework, direct observation and the potential to realize positive change. The experience will be useful to inform the process of coordinating research studies involving multiple stakeholders and results will help to guide service planning and policy decision making. TRIAL REGISTRATION: US Clinical Trial Registry NCT02307903. PMID- 27401346 TI - Developmental regulation of myeloerythroid progenitor function by the Lin28b-let 7-Hmga2 axis. AB - For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood. In this study, we find that expression of the heterochronic factor Lin28b decreases in common myeloid progenitors during hematopoietic maturation to adulthood in mice. This decrease in Lin28b coincides with accumulation of mature let-7 microRNAs, whose biogenesis is regulated by Lin28 proteins. We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. Conversely, deletion of Lin28b or ectopic activation of let-7 microRNAs in the fetal state induces a shift toward adult-like myeloid-dominant output. Furthermore, we identify Hmga2 as an effector of this genetic switch. These studies provide the first detailed analysis of the roles of endogenous Lin28b and let-7 in the timing of hematopoietic states during development. PMID- 27401351 TI - Request for organ donation without donor registration: a qualitative study of the perspectives of bereaved relatives. AB - BACKGROUND: In the Netherlands, consent from relatives is obligatory for post mortal donation. This study explored the perspectives of relatives regarding the request for consent for donation in cases without donor registration. METHODS: A content analysis of narratives of 24 bereaved relatives (14 in-depth interviews and one letter) of unregistered, eligible, brain-dead donors was performed. RESULTS: Relatives of unregistered, brain-dead patients usually refuse consent for donation, even if they harbour pro-donation attitudes themselves, or knew that the deceased favoured organ donation. Half of those who refused consent for donation mentioned afterwards that it could have been an option. The decision not to consent to donation is attributed to contextual factors, such as feeling overwhelmed by the notification of death immediately followed by the request; not being accustomed to speaking about death; inadequate support from other relatives or healthcare professionals, and lengthy procedures. CONCLUSION: Healthcare professionals could provide better support to relatives prior to donation requests, address their informational needs and adapt their message to individual circumstances. It is anticipated that the number of consenting families could be enlarged by examining the experience of decoupling and offering the possibility of consent for donation after circulatory death if families refuse consent for donation after brain-death. PMID- 27401352 TI - Effect of bevel direction on the success rate of ultrasound-guided radial arterial catheterization. AB - BACKGROUND: This study assessed the effect of bevel direction on the success rate of ultrasound guided radial artery catheterization. METHODS: A total of 204 patients requiring radial artery catheterization were randomly divided into bevel up (n = 102) and bevel-down (n = 102) groups. Success rate, cannulation time, and number of attempts were compared groups. RESULTS: In the bevel-down group, an arterial line was placed on the first attempt in 86 of 102 (84.3 %; 95 % confidence interval [CI] = 76 % to 90 %) patients versus 73 of 102 (71.6 %; 95 % CI = 62.1 % to 79.4 %) in the bevel-up group (p = 0.028). In the bevel-down group, the mean time to a successful radial arterial cannulation was 33.3 +/- 6.3 seconds (95 % CI = 32.1-34.6) versus 35.9 +/- 7.6 seconds (95 % CI = 34.4-37.2) in the bevel-up group (p = 0.011). The median score was 33.2 and interquartile range [IQR] was 10.9 (30.3-41.2) for the mean cannulation time in the bevel-up group. In the bevel-down group, the mean score was 32.3 (IQR 3.90, 30-33.9) for mean cannulation time. In the bevel-down group, 11 of 102 (7 %; 95 % CI = 0 to 16 %) patients developed a posterior wall puncture versus 22 of 102 ((21.6 %; 95 % CI = 14.7 to 17.2 %) in the bevel-up group. CONCLUSION: The bevel-down approach during ultrasound-guided radial artery catheterization exhibited a higher success with fewer complications compared to the bevel-up approach. TRIAL REGISTRATION: Clinical Research Information Service is Korean Clinical Trials Registry ( KCT0001836 ). It was registered retrospectively 30th Nov 2015. PMID- 27401353 TI - Is coffee consumption associated with a lower risk of hyperuricaemia or gout? A systematic review and meta-analysis. AB - OBJECTIVES: To examine the associations of coffee consumption with the serum uric acid (SUA) level, hyperuricaemia (HU) and gout. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: A comprehensive literature search up to April 2015, using PubMed and EMBASE databases, was conducted to identify the observational researches that examined the associations of coffee consumption with the SUA level, HU and gout. The standard mean difference (SMD), OR, relative risk (RR) and their corresponding 95% CIs for the highest and the lowest categories of coffee intake were determined. RESULTS: A total of 11 observational studies (6 cross-sectional, 3 cohort and 2 case-control studies) were included in this systematic review and meta-analysis. The combined SMD suggested that there was no significant difference between the highest and the lowest coffee intake categories in terms of the SUA level (SMD=-0.09, 95% CI 0.23 to 0.05; p=0.21). Meanwhile, the overall multivariable adjusted OR for HU showed no significant difference between the highest and the lowest coffee intake categories (OR=0.84, 95% CI 0.65 to 1.09; p=0.20). However, the overall multivariable adjusted RR for gout showed a significant inverse association between coffee consumption and the incidence of gout (RR=0.43, 95% CI 0.31 to 0.59, p<0.001). CONCLUSIONS: Current evidences are insufficient to validate the association between coffee consumption and a lower risk of HU. Owing to the limited number of studies, the available data show that coffee consumption may be associated with a lower risk of incident gout. Further well-designed prospective researches and randomised controlled trials are therefore needed to elaborate on these issues. PMID- 27401354 TI - Breast feeding and the weekend effect: an observational study. AB - OBJECTIVE: To compare the incidence of breast feeding by day of week of birth. DESIGN: Retrospective database study using 16 508 records from the 2005 and 2010 Infant Feeding Surveys. SETTING: England and Wales, UK. PARTICIPANTS: Mothers of a sample of births from among all registered births in the periods August September 2005 and August-October 2010. MAIN OUTCOME MEASURE: Incidence of breast feeding after birth. RESULTS: Among babies of mothers who left full-time education aged 16 or under, the incidence of breast feeding was 6.7 percentage points lower (95% CI 1.4 to 12.1 percentage points) for those born on Saturdays than for those born on Mondays-Thursdays. No such differences by day of week of birth were observed among babies of mothers who left school aged 17 or over. CONCLUSIONS: Breastfeeding policy should take into account differences in breast feeding by day of week of birth, which are apparent among low-educated mothers. Further research is needed to ascertain the reason for this finding. PMID- 27401355 TI - Exploration of the psychological impact and adaptation to cardiac events in South Asians in the UK: a qualitative study. AB - OBJECTIVE: There is little research on how different ethnic groups adapt after an acute cardiac event. This qualitative study explores between-ethnicity and within ethnicity variation in adaptation, and the psychological impact of an acute cardiac event among UK South Asian and white British people. SETTING: We purposively sampled people by ethnic group from general practices in London who had a new myocardial infarction, angina or acute arrhythmia in the preceding 18 months. PARTICIPANTS: We conducted 28 semistructured interviews for exploring the psychological symptoms, experiences and adaptations following a cardiac event among South Asians (Indian and Bangladeshi) in comparison to white British people. Data were analysed using a thematic 'framework' approach. RESULTS: Findings showed heterogeneity in experiences of the cardiac event and its subsequent psychological and physical impact. Adaptation to the event related predominantly to life circumstances, personal attitudes and employment status. Anxiety and low mood symptoms were common sequelae, especially in the Bangladeshi group. Indian men tended to normalise symptoms and the cardiac event, and reported less negative mood symptoms than other groups. Fear of physical exertion, particularly heavy lifting, persisted across the groups. Some people across all ethnic groups indicated the need for more psychological therapy postcardiac event. Socioeconomic circumstances, age and prior work status appeared to be more important in relation to adaptation after a cardiac event than ethnic status. CONCLUSIONS: Heterogeneity in views and experiences related to the socioeconomic background, age and work status of the participants along with some cultural influences. Rehabilitation programmes should be flexibly tailored for individuals in particular and where relevant, specific support should be provided for returning to work. PMID- 27401356 TI - Prospective audit to evaluate the potential of the coronial system to increase solid organ donation. AB - OBJECTIVES: Anecdotal evidence suggests that organ donation from deceased donors referred to the Coroner/Procurator Fiscal (PF) could be increased if all followed best practice. The aim of this prospective audit was to establish how referrals affected organ donation and to develop evidence-based guidelines to ensure that organ donation can be facilitated safely without interfering in the Coroner/PF's investigative process. DESIGN: Prospective audit. SETTING: All acute National Health Service Hospitals in the UK where deceased organ donation was considered. PARTICIPANTS: 1437 deceased patients who met the eligibility criteria for organ donation and were referred to Coroner/PF. MAIN OUTCOME MEASURES: Number of cases where permission for transplantation was given, number of organs where permission was refused and number of organs which might have been transplanted if all had followed best practice. RESULTS: Full permission for organ retrieval was given in 87% cases and partial permission in 9%. However, if full permission had been given where no autopsy was performed or restrictions seemed unjustified, up to 77 organs (22 lungs, 22 kidneys, 9 pancreases, 9 livers, 8 hearts and 7 small bowels) could have been available for transplant. CONCLUSIONS: Coroners/PFs and their officers show strong support for transplantation but improvement in practice could result in a small but significant increase in life-saving and life enhancing transplants. PMID- 27401357 TI - Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial. AB - OBJECTIVES: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD). DESIGN: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard). SETTING: Internet-based application. PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care. INTERVENTIONS: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes. MAIN OUTCOME MEASURES: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions. RESULTS: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists. CONCLUSIONS: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals. TRIAL REGISTRATION NUMBER: ISRCTN07479761; pre-results registration. PMID- 27401358 TI - Does a hospital admission in old age denote the beginning of life with a compromised health-related quality of life? A longitudinal study of men and women aged 65 years and above participating in the Stockholm Public Health Cohort. AB - OBJECTIVES: The objective of this study was to analyse how hospitalisation after the age of 60 affected individuals' health-related quality of life (HRQoL). The main hypothesis was that a hospital admission in old age can be seen as a proxy of ill health and possibly as a health divider, separating life into a healthy and an unhealthy part. The extent to which this is true depends on which disease individuals face and how functional ability and HRQoL are affected. SETTINGS: This was a longitudinal study, based on an older cohort of individuals who participated in the Stockholm Public Health Cohort (SPHC) survey in 2006; the survey took place in Stockholm, Sweden. Information regarding hospitalisations and deaths, which is available through Swedish administrative registers, was linked to the survey from the National Patient Register and Cause of Death Register. PARTICIPANTS: 2101 individuals, 65+ years old at inclusion, with no previous hospitalisations at baseline (2006), were followed for 4 years until 2010 (end of follow-up). PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL was assessed through a utility index derived from the EuroQol 5D questionnaire, at baseline and at 2010. The change in HRQoL after admission(s) to the hospital was estimated as the difference between the 2010 and 2006 levels using linear regression, also considering several covariates. RESULTS: A single hospitalisation did not reduce individuals' HRQoL, either for men or women. On the other hand, multiple any-cause hospitalisations reduced HRQoL between 3.2% and 6.5%. When looking into hospitalisations for specific causes, such as hip fractures, a decrease in HRQoL was observed as well; however, conclusions regarding this were impeded by the small sample size. CONCLUSIONS: Hospital admissions in old age may indicate a shift from a healthy life to a life of compromised health when considering their frequency and cause over a period of time. PMID- 27401359 TI - Comparative efficacy and acceptability of first-generation and second-generation antidepressants in the acute treatment of major depression: protocol for a network meta-analysis. AB - INTRODUCTION: Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression. METHODS AND ANALYSIS: We will include all randomised controlled trials reported as double-blind and comparing one active drug with another or with placebo in the acute phase treatment of major depression in adults. We are interested in comparing the following active agents: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The main outcomes will be the proportion of patients who responded to or dropped out of the allocated treatment. Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random effects network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. To rank the various treatments for each outcome, we will use the surface under the cumulative ranking curve and the mean ranks. We will employ local as well as global methods to evaluate consistency. We will fit our model in a Bayesian framework using OpenBUGS, and produce results and various checks in Stata and R. We will also assess the quality of evidence contributing to network estimates of the main outcomes with the GRADE framework. ETHICS AND DISSEMINATION: This review does not require ethical approval. PROSPERO REGISTRATION NUMBER: CRD42012002291. PMID- 27401360 TI - SmartPill(r) as an objective parameter for determination of severity and duration of postoperative ileus: study protocol of a prospective, two-arm, open-label trial (the PIDuSA study). AB - INTRODUCTION: Postoperative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill((r)), a capsule which frequently measures pH value, temperature and intraluminal pressure after swallowing, offers an elegant option for analysing gastrointestinal (GI) transit times and smooth muscle activity in vivo. As the use in patients in the first months after AS is not covered by the marketing authorisation, we aim to investigate the safety and feasibility of the SmartPill((r)) immediately after surgery. Additionally, we analyse the influence of prokinetics and laxatives as well as standardised physiotherapy on postoperative bowel contractility, as scientific evidence of its effects is still lacking. METHODS AND ANALYSIS: The PIDuSA study is a prospective, single-centre, two-arm, open-label trial. The SmartPill((r)) will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill((r)) in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggests that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of postoperative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill((r)) to evaluate its significance as an objective parameter for assessing POI severity. Additionally, effects of prokinetics, laxatives and physiotherapy on postoperative peristaltic activity recorded by the SmartPill((r)) will be analysed. ETHICS AND DISSEMINATION: The protocol was approved by the federal authority (94.1.05-5660-8976) and the local ethics committee (092/14-MPG). Findings will be disseminated through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT02329912; Pre-results. PMID- 27401361 TI - Effectiveness of the Assessment of Burden of COPD (ABC) tool on health-related quality of life in patients with COPD: a cluster randomised controlled trial in primary and hospital care. AB - OBJECTIVE: Assessing the effectiveness of the Assessment of Burden of COPD (ABC) tool on disease-specific quality of life in patients with chronic obstructive pulmonary disease (COPD) measured with the St. George's Respiratory Questionnaire (SGRQ), compared with usual care. METHODS: A pragmatic cluster randomised controlled trial, in 39 Dutch primary care practices and 17 hospitals, with 357 patients with COPD (postbronchodilator FEV1/FVC ratio <0.7) aged >=40 years, who could understand and read the Dutch language. Healthcare providers were randomly assigned to the intervention or control group. The intervention group applied the ABC tool, which consists of a short validated questionnaire assessing the experienced burden of COPD, objective COPD parameter (eg, lung function) and a treatment algorithm including a visual display and treatment advice. The control group provided usual care. Researchers were blinded to group allocation during analyses. Primary outcome was the number of patients with a clinically relevant improvement in SGRQ score between baseline and 18-month follow-up. Secondary outcomes were the COPD Assessment Test (CAT) and the Patient Assessment of Chronic Illness Care (PACIC; a measurement of perceived quality of care). RESULTS: At 18-month follow-up, 34% of the 146 patients from 27 healthcare providers in the intervention group showed a clinically relevant improvement in the SGRQ, compared with 22% of the 148 patients from 29 healthcare providers in the control group (OR 1.85, 95% CI 1.08 to 3.16). No difference was found on the CAT (-0.26 points (scores ranging from 0 to 40); 95% CI -1.52 to 0.99). The PACIC showed a higher improvement in the intervention group (0.32 points (scores ranging from 1 to 5); 95% CI 0.14 to 0.50). CONCLUSIONS: This study showed that use of the ABC tool may increase quality of life and perceived quality of care. TRIAL REGISTRATION NUMBER: NTR3788; Results. PMID- 27401362 TI - Lifestyle-related diseases following the evacuation after the Fukushima Daiichi nuclear power plant accident: a retrospective study of Kawauchi Village with long term follow-up. AB - OBJECTIVES: Kawauchi Village lies 20 km west of the Fukushima Daiichi nuclear power plant. On 16 March 2011, evacuation was ordered due to the threat of radiological exposure, and was lifted in April 2012. In this study, we aimed to evaluate the predisaster and postdisaster health status of the Kawauchi Villagers, measured by routine yearly physical examinations. METHODS: We analysed the annual health examination data of residents of Kawauchi Village from 2008 to 2013, as available from the Japanese National Health Insurance system. Data from 2011 were not available due to the disaster. Since the health data included the same participants repeatedly from year to year, the sample was non-independent and generalised estimated equation modelling was used. A predisaster time period (2008-2010) was categorised for comparison with postdisaster 2012 and 2013. The outcome examined was the prevalence of metabolic disease, and was adjusted for confounding factors. RESULTS: Data for 20.6%-25.9% of the total residents were available in this period. In 2013, the prevalence of metabolic syndrome (from 17.0% to 25.2%, p<0.001), diabetes (from 11.3% to 17.0%, p<0.001), dyslipidaemia (from 43.2% to 56.7%, p<0.0001), hyperuricaemia (from 5.2% to 8.4%, p=0.006) and chronic kidney disease (from 16.1% to 26.7%, p<0.001) was found to be elevated significantly compared to predisaster years, while that of obesity or hypertension did not change. CONCLUSIONS: The present follow-up study for Kawauchi Village revealed an increase in lifestyle-related disease following the March 2011 disaster and subsequent evacuation, and this trend still continues 2 years later. PMID- 27401363 TI - Improving advance care planning for English-speaking and Spanish-speaking older adults: study protocol for the PREPARE randomised controlled trial. AB - INTRODUCTION: Advance care planning (ACP) is a process that allows patients to identify their goals for medical care. Traditionally, ACP has focused on completing advance directives; however, we have expanded the ACP paradigm to also prepare patients to communicate their wishes and make informed decisions. To this end, we created an ACP website called PREPARE (http://www.prepareforyourcare.org) to prepare diverse English-speaking and Spanish-speaking older adults for medical decision-making. Here, we describe the study protocol for a randomised controlled efficacy trial of PREPARE in a safety-net setting. The goal is to determine the efficacy of PREPARE to engage diverse English-speaking and Spanish-speaking older adults in a full spectrum of ACP behaviours. METHODS AND ANALYSIS: We include English-speaking and Spanish-speaking adults from an urban public hospital who are >=55 years old, have >=2 chronic medical conditions and have seen a primary care physician >=2 times in the last year. Participants are randomised to the PREPARE intervention (review PREPARE and an easy-to-read advance directive) or the control arm (only the easy-to-read advance directive). The primary outcome is documentation of an advance directive and/or ACP discussion. Secondary outcomes include ACP behaviour change processes measured with validated surveys (eg, self efficacy, readiness) and a broad range of ACP actions (eg, choosing a surrogate, identifying goals for care, discussing ACP with clinicians and/or surrogates). Using blinded outcome ascertainment, outcomes will be measured at 1 week and at 3, 6 and 12 months, and compared between study arms using mixed-effects logistic regression and mixed-effects linear, Poisson or negative binomial regression. ETHICS AND DISSEMINATION: This study has been approved by the appropriate Institutional Review Boards and is guided by input from patient and clinical advisory boards and a data safety monitoring board. The results of this study will be disseminated to academic and community stakeholders. TRIAL REGISTRATION NUMBERS: NCT01990235; NCT02072941; Pre-results. PMID- 27401364 TI - A protocol for a randomised controlled trial investigating the effect of increasing Omega-3 index with krill oil supplementation on learning, cognition, behaviour and visual processing in typically developing adolescents. AB - INTRODUCTION: The influence of n-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation on brain functioning is debated. Some studies have found positive effects on cognition in children with learning difficulties, elderly people with cognitive impairment and depression scores in depressed individuals. Other studies have found null or negative effects. Observational studies in adolescents have found positive associations between fish consumption (containing n-3 LCPUFAs) and academic achievement. However, intervention studies in typically developing adolescents are missing. OBJECTIVE: The goal of this study is to determine the influence of increasing Omega-3 Index on cognitive functioning, academic achievement and mental well-being of typically developing adolescents. METHODS AND DATA ANALYSIS: Double-blind, randomised, placebo controlled intervention; 264 adolescents (age 13-15 years) attending lower general secondary education started daily supplementation of 400 mg eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) in cohort I (n=130) and 800 mg EPA+DHA in cohort II (n=134) or a placebo for 52 weeks. Recruitment took place according to a low Omega-3 Index (<5%). The Omega-3 Index was monitored via a finger prick at baseline and after 3, 6 and 12 months. The supplement dose was adjusted after 3 months (placebo analogously) to reach an Omega-3 Index of 8-11%. At baseline, 6 and 12 months, a neuropsychological test battery, a number of questionnaires and a standardised math test (baseline and 12 months) were administered. School grades were collected. In a subsample, sleep quality and quantity data (n=64) and/or eye-tracking data (n=33) were collected. ETHICS AND DISSEMINATION: Food2Learn is performed according to Good Clinical Practice. All data collected are linked to participant number only. The results will be disseminated on group level to participants and schools. The results will be presented at conferences and published in peer-reviewed journals. The study is approved by the Medical Ethical Committee of Atrium-Orbis-Zuyd Hospital and is registered at the Netherlands Trial Register (NTR4082). TRIAL REGISTRATION NUMBERS: NTR4082 and NCT02240264; Pre-results. PMID- 27401366 TI - Perceptions and experiences of the implementation, management, use and optimisation of electronic prescribing systems in hospital settings: protocol for a systematic review of qualitative studies. AB - INTRODUCTION: There is increasing evidence that electronic prescribing (ePrescribing) or computerised provider/physician order entry (CPOE) systems can improve the quality and safety of healthcare services. However, it has also become clear that their implementation is not straightforward and may create unintended or undesired consequences once in use. In this context, qualitative approaches have been particularly useful and their interpretative synthesis could make an important and timely contribution to the field. This review will aim to identify, appraise and synthesise qualitative studies on ePrescribing/CPOE in hospital settings, with or without clinical decision support. METHODS AND ANALYSIS: Data sources will include the following bibliographic databases: MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, Social Policy and Practice via Ovid, CINAHL via EBSCO, The Cochrane Library (CDSR, DARE and CENTRAL databases), Nursing and Allied Health Sources, Applied Social Sciences Index and Abstracts via ProQuest and SCOPUS. In addition, other sources will be searched for ongoing studies (ClinicalTrials.gov) and grey literature: Healthcare Management Information Consortium, Conference Proceedings Citation Index (Web of Science) and Sociological abstracts. Studies will be independently screened for eligibility by 2 reviewers. Qualitative studies, either standalone or in the context of mixed-methods designs, reporting the perspectives of any actors involved in the implementation, management and use of ePrescribing/CPOE systems in hospital-based care settings will be included. Data extraction will be conducted by 2 reviewers using a piloted form. Quality appraisal will be based on criteria from the Critical Appraisal Skills Programme checklist and Standards for Reporting Qualitative Research. Studies will not be excluded based on quality assessment. A postsynthesis sensitivity analysis will be undertaken. Data analysis will follow the thematic synthesis method. ETHICS AND DISSEMINATION: The study does not require ethical approval as primary data will not be collected. The results of the study will be published in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: CRD42016035552. PMID- 27401365 TI - Understanding the role of the immune system in adolescent idiopathic scoliosis: Immunometabolic CONnections to Scoliosis (ICONS) study protocol. AB - INTRODUCTION: Adolescent idiopathic scoliosis (AIS) affects up to 3% of children around the world. There is limited knowledge of AIS aetiopathogenesis, and this evidence is needed to develop new management strategies. Paraspinal muscle in AIS demonstrates evidence of differential fibrosis based on curve sidedness. Fibrosis is the hallmark of macrophage-driven inflammation and tissue remodelling, yet the mechanisms of fibrosis in paraspinal muscle in AIS are poorly understood. OBJECTIVES: The primary objective of this study is to determine the influence of curve sidedness on paraspinal muscle inflammation. Secondary objectives include defining the mechanisms of macrophage homing to muscle, and determining muscle macrophage crosstalk in muscle fibrosis in AIS. METHODS AND ANALYSIS: This is a cross-sectional study conducted in a tertiary paediatric centre in Hamilton, Ontario, Canada. We will recruit boys and girls, 10-17 years of age, who are having surgery to correct AIS. We will exclude children who have an active infection or are on immunosuppressive therapies within 2 weeks of surgery, smokers and pregnant girls. Paraspinal muscle biopsies will be obtained at the start of surgery. Also, blood and urine samples will be collected from participants, who will fill questionnaires about their lifestyle. Anthropometric measures will also be collected including height, weight, waist and hip circumferences. ETHICS AND DISSEMINATION: This study has received ethics authorisation by the institutional review board. This work will be published in peer-reviewed journals and will be presented in oral and poster formats at scientific meetings. DISCUSSION: This study will explore the mechanisms of paraspinal muscle inflammation, remodelling and fibrosis in AIS. This will help identify pathways and molecules as potential therapeutic targets to treat and prevent AIS. It may also yield markers that predict scoliosis progression and response to treatment in these children. PMID- 27401367 TI - Protocol to describe the analysis of text-based communication in medical records for patients discharged from intensive care to hospital ward. AB - INTRODUCTION: Effective communication during hospital transitions of patient care is fundamental to ensuring patient safety and continuity of quality care. This study will describe text-based communication included in patient medical records before, during and after patient transfer from the intensive care unit (ICU) to a hospital ward (n=10 days) by documenting (1) the structure and focus of physician progress notes within and between medical specialties, (2) the organisation of subjective and objective information, including the location and accessibility of patient data and whether/how this changes during the hospital stay and (3) missing, illegible and erroneous information. METHODS: This study is part of a larger mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. Medical records will be collected and photocopied for each consenting patient for a period of up to 10 consecutive days, including the final 2 days in the ICU, the day of transfer and the first 7 days on the ward (n=10 days). Textual analysis of medical record data will be completed by 2 independent reviewers to describe communication between stakeholders involved in ICU transfer. ETHICS AND DISSEMINATION: Research ethics board approval has been obtained at all study sites, including the coordinating study centre (which covers 4 Calgary-based sites; UofC REB 13-0021) and 6 additional study sites (UofA Pro00050646; UBC PHC Hi4-01667; Sunnybrook 336-2014; QCH 20140345-01H; Sherbrooke 14-172; Laval 2015-2171). Findings from this study will inform the development of an evidence-based tool that will be used to systematically analyse the series of notes in a patient's medical record. PMID- 27401368 TI - Glycosylated haemoglobin as a predictor of cardiovascular events and mortality: a protocol for a systematic review and meta-analysis. AB - INTRODUCTION: Glycosylated haemoglobin level (HbA1c) is an indicator of the average blood glucose concentrations over the preceding 2-3 months and is used as a convenient and well-known biomarker in clinical practice. Currently, epidemiological evidence suggests that HbA1c level is an independent risk factor for cardiovascular events such as myocardial infarction, stroke, coronary heart disease and heart failure. This protocol aim is to conduct a systematic review and meta-analysis to determine relationships of HbA1c levels with cardiovascular outcomes and cause of death, and to analyse the range of HbA1c levels that is a predictor of cardiovascular disease and/or mortality based on data from published observational studies. METHODS AND ANALYSIS: The search will be conducted using Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception. Observational studies written in Portuguese, Spanish or English will be included. The Quality In Prognosis Studies tool will be used to assess the risk of bias for the studies included in the systematic review or meta-analysis. HRs for cardiovascular outcomes and causes of death with 95% CIs will be determined as primary outcomes. Subgroup analyses will be performed based on cardiovascular outcomes, cause of death studied, and type of population included in the studies. ETHICS AND DISSEMINATION: This systematic review will synthesise evidence on the potential of using HbA1c level as a prognostic marker for cardiovascular disease outcomes and/or mortality. The results will be disseminated by publication in a peer-reviewed journal. Ethics approval will not be needed because the data used for this systematic review will be obtained from published studies and there will be no concerns about privacy. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015032552. PMID- 27401369 TI - Diagnosis and management of polycystic ovary syndrome in the UK (2004-2014): a retrospective cohort study. AB - OBJECTIVE: To estimate the incidence and prevalence of polycystic ovary syndrome (PCOS) in UK primary care and investigate prescribing patterns before and after a PCOS diagnosis. DESIGN: Retrospective cohort study. SETTING: UK primary care (2004-2014). PARTICIPANTS: Women aged 15-45 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence and prevalence of diagnosed PCOS and probable PCOS (ie, those without a confirmed diagnosis but with at least 2 PCOS features recorded within 3 years). Among women with diagnosed or probable PCOS, the prevalence of prescribing of drugs typically used to treat PCOS was calculated prior to and in the 24 months after the diagnosis of PCOS. RESULTS: We identified 7233 women with PCOS diagnoses and 7057 women with records suggestive of probable PCOS, corresponding to incidence rates of 0.93 and 0.91 per 1000 person-years at risk (PYAR) and an overall rate of 1.84 per 1000 PYAR. Women aged 20-24 years and women living in deprived areas had the highest incidence of PCOS. The prevalence of PCOS in 2014 was ~2%. The proportion of women with a prescription in the 24 months after their PCOS index date varied by drug type: 10.2% metformin, 15.2% combined oral contraceptives, 18.8% acne-related treatments, 1.93% clomiphene, 1.0% spironolactone, 0.28% cyproterone and 3.11% eflornithine. Acne-related treatments were more commonly used to treat probable (28.3%) than diagnosed (12.3%) cases, while metformin was prescribed much more commonly in diagnosed cases. CONCLUSIONS: In conclusion, compared to rates estimated in community samples, the incidence and prevalence of women presenting in primary care with PCOS diagnoses and features are low, indicating that PCOS is an under-recognised condition. Although considerable variation is observed in treatments prescribed to women with PCOS, the treatments initiated following a confirmed diagnosis generally reflect the long-term prognostic concerns raised in PCOS consensuses. PMID- 27401371 TI - Juvenile temporal arteritis with eosinophilia associated with systemic sclerosis. PMID- 27401370 TI - p53 Loses grip on PIK3CA expression leading to enhanced cell survival during platinum resistance. AB - Tumour suppressor p53, a master transcriptional regulator determines cell fate through preferential activation/repression of a myriad of genes during stress. Till date, activation and preferential binding of p53 on different promoters was reported to be influenced by the nature, strength and duration of stress which mediates its post translational modifications. Cisplatin, a widely used cytotoxic drug represses PIK3CA promoter activity and attenuates PI3K/AKT cell survival pathway through p53 activation in sensitive cells. However, very little is understood about the overall mechanism of p53-PIK3CA interaction and influence of p53 on the transcriptional status of PIK3CA during cisplatin resistance. Here we showed that cisplatin could dynamically alter p53 occupancy between the p53 binding sequences present in PIK3CA promoter in ovarian and breast cancer cells. This altered occupancy is dictated by higher acetylation and hyper phosphorylation at serine 15, serine 20 and serine 46 residues. Interestingly, cisplatin resistant cells when challenged with cisplatin demonstrated abolished PIK3CA promoter attenuation, low level of p53 binding, and loss of p53 serine 46 phosphorylation. A phosphorylation deficient S46A mutant failed to repress PIK3CA in p53 deficient cells. Elevated expression of Bcl2, P27 and cFLIP indicated a pro-survival state in these resistant cells. Non-invasive real time imaging using two different luciferase reporters showed that cisplatin could simultaneously induce PIK3CA attenuation and p53 activation with growth regression in sensitive tumours but not in the resistant tumours where only low level of p53 activation and sustained growth was observed. This is the first report on phosphorylation of p53 serine 46 as a modulator of p53-PIK3CA promoter interaction which influences altered binding of p53 at different consensus sequences in the same promoter in response to chemotherapeutic stress. Absence of such modulation in resistant cellular milieu influences cellular homoeostasis in platinum-resistant cells probably due to altered post translational modification of p53. PMID- 27401372 TI - [Inappropriate medication use among Chilean older people]. AB - BACKGROUND: Inappropriate medication use in older people is an important source of adverse events and complications. AIM: To determine the frequency of inappropriate medication use in the general population. MATERIAL AND METHODS: As part of the 2010 Chilean National Health Survey, 1,048 persons aged 65 years or more were interviewed about medication use. The information obtained was analyzed using standardized Beer?s criteria, adapted for the Chilean population, to define inappropriate medication use. A logistic regression model was performed to define risk factors for inappropriate medication use. RESULTS: Ten percent of subjects had a high risk of inappropriate medication use. The most common medications used were chlorphenamine, amitriptyline, diazepam, chlorpromazine, chlordiazepoxide and piroxicam. The risk factors detected were female gender, polypharmacy and a bad health self-perception. CONCLUSIONS: Inappropriate medication use is common among Chilean older people and should be discouraged. PMID- 27401373 TI - [Assessment of the Chilean rural practitioner program by its participating physicians]. AB - BACKGROUND: Rural areas have scarce medical resources. Initiatives to address this situation in Latin America exist, but have been poorly evaluated. The Chilean Rural Practitioner Program, a policy of recruitment and retention of physicians in rural areas, has been stable over time. AIM: To examine how physicians who participate in this program evaluate it. MATERIAL AND METHODS: Nationally representative cross sectional study. Physicians were chosen to respond online or by telephone a specially designed questionnaire about the Program. RESULTS: 202 participants answered (response rate of 60%). The overall experience was evaluated with 5.75 points (in a 1 to 7 scale). Participants gave the best scores to climatic conditions and economic income, and rated infrastructure, human resources and workload the worst. The evaluation of social relationships at the destination place was the only condition associated significantly with the overall assessment of the experience. Seventy percent of physicians would return to the destination place as a specialist. The value given to social relations and infrastructure were associated positively with this potential return. CONCLUSIONS: Overall, the experience was positively evaluated. This study provides information to improve retention policies for human resources for health care in rural areas. PMID- 27401374 TI - Reversion of methacholine induced bronchoconstriction with inhaled diazepam in patients with asthma. AB - BACKGROUND: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. AIM: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. PATIENTS AND METHODS: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. RESULTS: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. CONCLUSIONS: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma. PMID- 27401375 TI - [Intravenous thrombolysis for ischemic stroke: Experience in 54 patients]. AB - BACKGROUND: Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) reduces disability in patients with ischemic stroke. However, its implementation in Chilean public general hospitals has been slow and faces some difficulties. AIM: To analyze the results of an intravenous thrombolysis protocol implementation in a public general hospital. MATERIAL AND METHODS: During a lapse of 28 months a standardized protocol for intravenous thrombolysis implemented in the emergency room of a public hospital, was prospectively evaluated. Fifty four patients with ischemic stroke were treated and assessed three months later as outpatients. RESULTS: At three months of follow-up, 66.4% of patients subjected to thrombolysis had a favorable evolution, defined as having 0 to 1 points in the modified Rankin scale. Intracerebral hemorrhage rate was 11.1%, including 5.5% of symptomatic intracerebral hemorrhage. Four percent of patients had systemic bleeding complications after thrombolysis. The mortality rate was 14.8%. CONCLUSIONS: The success rates, mortality, and complications rate were comparable to the results obtained in international studies, despite of the absence of a stroke unit to manage stroke and its complications. PMID- 27401376 TI - [Usefulness of upper gastrointestinal series to detect leaks in the early postoperative period of bariatric surgery]. AB - BACKGROUND: Postoperative leaks are the most undesirable complication of bariatric surgery and upper gastrointestinal (GI) series are routinely ordered to rule them out. Despite the published literature recommending against its routine use, it is still being customarily used in Chile. AIM: To examine the usefulness of routine upper GI series using water-soluble iodinated contrast media for the detection of early postoperative leaks in patients undergoing bariatric surgery. MATERIAL AND METHODS: A cohort of 328 patients subjected to bariatric surgery was followed from October 2012 to October 2013. Most of them underwent sleeve gastrectomy. RESULTS: Upper GI series on the first postoperative day were ordered to 308 (94%) patients. Postoperative leaks were observed in two patients, with an incidence of 0.6%. The sensitivity for upper GI series detection of leak was 0% and the negative predictive value was 99%. CONCLUSIONS: Routine upper GI series after bariatric surgery is not useful for the diagnosis of postoperative leak, given the low incidence of this complication and the low sensitivity of the technique. PMID- 27401377 TI - [Cost effectiveness of a theoretical cardiac rehabilitation program after myocardial infarction]. AB - BACKGROUND: Secondary prevention programs are an essential part of comprehensive care of patients with cardiovascular disease (CVD), and its effectiveness in reducing morbidity or mortality has been proved. AIM: To determine the cost effectiveness of a theoretical comprehensive cardiac rehabilitation (CCR) outpatient program after Myocardial Infarction, to be implemented in a Chilean Public Health System. MATERIAL AND METHODS: We designed a theoretical protocol of a CCR program based on recommendations of international guidelines, but adapted to local needs. A cost analysis was developed. Life years due to premature death were estimated with and without participation in CCR. The gained life-years and cost-effectiveness of the program were thus calculated. RESULTS: The annual cost of cardiac rehabilitation center is $ 64,407,065 Chilean pesos (CLP). The Incremental Cost Effectiveness Ratio (ICER) considering a reduction of late mortality of 25%, is $ 475,209.7 CLP per year of life gained. Since this figure is lower than one unit of per capita gross domestic product, the intervention is considered very cost-effective. CONCLUSIONS: A comprehensive cardiac rehabilitation program after myocardial infarction is very cost-effective in the context of its implementation in a public health service. PMID- 27401378 TI - [Smoking and alcohol use among Chilean teenagers aged 10 to 14 years]. AB - BACKGROUND: Smoking and alcohol use are risky behaviors that can start early in life. AIM: To determine the lifetime prevalence of tobacco and alcohol use in adolescents aged 10 to 14 years and related factors. SUBJECTS AND METHODS: A survey about smoking and alcohol use was answered by 1,392 teenagers aged 10 to 14 years (46% women) from seven schools in a small city near Santiago. Personal, family, and school factors were evaluated through self-report scales. Smoking and alcohol use, as dichotomous dependent variables, were defined as having consumed any of these substances throughout life. Prevalence was calculated as percentages with 95% confidence intervals. Association analyses were conducted using multivariable logistic regression models. RESULTS: Six and eleven percent of participants reported having smoked and used alcohol in their life, respectively. Smoking was associated with age, having behavioral problems, mothers? smoking, perceiving that parents had drug problems, and not living with both parents. Alcohol use was mainly associated with age, having behavioral problems, perceiving that other students consumed drugs, alcohol use by both parents, and perceiving a lack of family support. CONCLUSIONS: Tobacco and alcohol use is highly prevalent in adolescents aged 10-14 years. There were common risk factors for smoking and alcohol use such as age and having behavioral problems, while other factors were more specific such as mothers? smoking, or parental alcohol use. PMID- 27401379 TI - [Obesity, a risk factor for ascending bacterial infection during pregnancy]. AB - BACKGROUND: Obesity in pregnancy is associated with significantly higher rates of infection. AIM: To compare the infectious morbidity in pregnant women with normal and altered body mass index (BMI). MATERIAL AND METHODS: Cross sectional retrospective study of 6,150 patients who had delivery or second trimester abortion during 2012. The patients were classified according to BMI as underweight, normal weight, overweight and obese. We compared the frequency of pregnancy and perinatal complications related to ascending bacterial infection (ABI). The data was obtained from the hospital?s databases. RESULTS: Obese patients had higher rates of pregnancy and perinatal complications related to ABI compared to patients with normal weight. The odds ratios (OR) and 95% confidence intervals (CI) for second trimester abortion were 3.45 (1.63-7.31) p < 0.01, for preterm delivery 2.42 (1.51-3.87) p < 0.01, for labor and puerperium infections 3.42 (2.06-5.68) p < 0.01 and for early neonatal infectious and perinatal mortality 4.46 (1.75-11.37) p < 0.01. A logistic regression analysis revealed that obesity is an independent risk factor for second trimester abortion related to ABI with an OR of 3.18 (CI 95% 1.46-6.91), premature delivery related to ABI with an OR of 2.51 (CI 95% 1.54-4.09) and for delivery and postpartum infections with an OR of 4.44 (CI 95% 2.62 to 7.51). CONCLUSIONS: Obese pregnant women had a 2.5 to 4.5 times increased risk of infectious morbidity compared to normal weight patients. Obesity is an independent risk factor for second trimester abortion and preterm delivery related to ABI and delivery and postpartum infectious. PMID- 27401380 TI - [Recent case law about the right to die]. AB - This paper reviews the sentences dictated between 1993 and 2002 by the Supreme Courts of Canada and the Unites States, the House of Lords and Supreme Court of the United Kingdom and the European Human Rights Court, about the validity of the legal prohibition of assistance for suicide. These sentences constituted a judicial consensus about the right to die. This consensus recognized the legal right of patients to reject medical treatments but did not recognize the right to be assisted by a physician to commit suicide. This exclusion is changing in the recent case law of Canada and the United Kingdom, which accepts the fundamental right of terminal patients to medically assisted suicide. PMID- 27401381 TI - [Towards an integral management of inflammatory bowel disease]. AB - Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with medical and psychological complications. Addressing psychosocial aspects of treatment, such as quality of care and disability remains a challenge. The quality of care for IBD patients is not optimal at the present time and there is a variation in the care provided by specialists. Therefore, it is necessary to develop well defined quality indicators to assure the delivery of an adequate care to these patients. The delivery of healthcare for IBD patients is often complex and requires multidisciplinary teams. The ultimate objectives in the treatment of IBD should be to prevent bowel damage, reduce long-term disability and maintain a normal quality of life. PMID- 27401382 TI - [Reality and challenges of the oral health for older adults in Chile and the role of a new discipline: geriatric dentistry]. AB - Chile is experiencing one of the fastest aging processes in Latin America. The implications derived from this phenomenon involve many aspects of the society, especially health care. In particular, insufficient oral health coverage in the country limits oral care provision for a population with a high prevalence and severity of oral diseases. These conditions include dental caries, periodontal disease, tooth loss, defective prostheses, oral mucosa lesions and xerostomia, among others, and strongly affect quality of life of the elderly population. Furthermore, dental curriculum of most dental schools lack specific training of students in geriatric dentistry or gerodontology. Hence, newly graduated professionals are not competent to satisfy the needs of this growing and increasingly demanding population of older adults. Within this demanding context, Chile may find the potential to become a model and referent to deal with the challenge, incorporating innovative changes in education and public health strategies for the older population by an interdisciplinary approach. PMID- 27401383 TI - [History of scrofula: from humoral dyscrasia to consumption]. AB - The term ?scrofula? was used for a long time to designate a chronic swelling of cervical lymph nodes. This paper outlines the prevalent ideas on the nature, pathogenesis and the treatment of this disorder, from classical Greek medicine up to the 18th century. A Hippocratic treatise regarded scrofula as produced by an accumulation of phlegm, with a consequent imbalance or dyscrasia of the body humors. It was believed that it could heal spontaneously; but it could also soften, open through the skin and have an obstinate course. The treatment consisted mainly on local applications, incision to evacuate the soft content, or extirpation of the abnormal mass. In France and England, crowds of scrofulous patients were touched by the kings who were supposed to have a hereditary miraculous power to cure the disease. A Medieval text mentioned that scrofula could also affect other parts of the body. In the 17th century, scrofula was reputed as a frequent condition and was attributed to blood acrimony which coagulated in spongy organs. It was associated to phthisis or consumption due to the lethal outcome in some patients and to a cheese-like appearance of the pulmonary and the scrofulous lesions. PMID- 27401384 TI - [Association between microRNA single nucleotide polymorphisms and the risk of hepatocellular carcinoma]. AB - BACKGROUND: Hepatocellular carcinoma (HCC) has a high morbidity and mortality. Single nucleotide polymorphisms (SNPs) of microRNA (miRNA) may be associated with the susceptibility to develop certain malignant tumors. AIM: To study the association between SNPs of miRNA and hepatocellular carcinoma in peripheral blood samples. MATERIAL AND METHODS: Three SNPs in miRNA were studied in peripheral blood samples of 498 patients with HCC and 520 controls. RESULTS: A significant association was observed between rs13299349 in miRNA3152 and HCC. AA genotype or A allele were significantly associated with increased risk of HCC. A allele was associated with the size and number of tumor foci. There was also a relationship between rs10061133 in miRNA449b and HCC. The G allele was significantly associated with increased risk of HCC compared with A allele. CONCLUSIONS: This study links rs13299349 in miRNA3152 and rs10061133 in miRNA449b with the risk of developing HCC. PMID- 27401385 TI - [Chronic kidney disease associated with Poems syndrome: Report of one case]. AB - POEMS syndrome is characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes. We report a woman with the syndrome, who had peripheral polyneuropathy, osteosclerotic myeloma, monoclonal IgA elevation, hypothyroidism, hypogonadotrophic hypogonadism, hyperprolactinemia, adrenal insufficiency, hepatosplenomegaly, lymphadenopathy, thyroid and parotid enlargement, Castleman?s disease, papilledema, stiff and hyperpigmented skin, white nails, clubbing, ascites and chronic diarrhea. She had also a nephropathy characterized by microscopic hematuria, proteinuria, renal insufficiency and a unilateral kidney retraction. She was treated with melphalan and prednisone, achieving remission of the disease and nephropathy. She survived twelve years and died due to a myocardial infarction 20 years after POEMS diagnosis. PMID- 27401386 TI - [Cerebellar hemangioblastoma and thrombocytopenia: Report of one case]. AB - The association between vascular tumors and thrombocytopenia is rare. Kasabach Merritt Syndrome is seen in childhood and is characterized by hemangiomas and thrombocytopenia. A 42 years-old man with a cerebellar hemangioblastoma and thrombocytopenia, admitted with a subarachnoid hemorrhage is reported. The patient was operated and required a splenectomy to manage the thrombocytopenia. After the splenectomy the patient developed a subdural hematoma that was operated. Despite the surgical treatment, the patient died. PMID- 27401387 TI - [Suicide attempts and self inflicted harm: a one year follow up of risk behaviors among out of treatment cocaine users]. AB - BACKGROUND: Cocaine users tend to have a higher frequency of risk behaviors. AIM: To compare risk behaviors of out -of -treatment Cocaine Base Paste (CBP) and Cocaine Hydrochloride (CH) users, by means of Privileged Access Interviewing in a one- year prospective study. MATERIAL AND METHODS: Twenty -eight interviewers were trained to recruit and administer a questionnaire on substance use patterns and related risk behaviors. Intentioned sampling was carried out in four municipalities of Santiago, Chile. Subjects who used CBP (group 1) or CH (group 2) at least once in the last month, with primary current use of CBP (group 1) or CH (group 2), and without treatment for substance abuse in the last six months were interviewed. Generalized Estimating Equations (GEE) were employed to compare risk behaviors during follow -up. RESULTS: Four hundred and two of 467 subjects (86.1%) were followed up for one year. CBP users (n = 204) reported greater frequency of self -inflicted injuries (Odds Ratio (OR): 1.97 [95% confidence intervals (CI): 1.07-3.66]) and suicide attempts (OR: 2.68 [95% CI: 1.19-6.01]) than CH users. CONCLUSIONS: CBP users had a greater frequency of self -inflicted injuries and suicide attempts, both life threatening risk behaviors, than CH users. This profile shows the high vulnerability of CBP users and should encourage further research and design of outreach interventions, particularly focused on this group. PMID- 27401388 TI - [ETESA, spheres and STS]. PMID- 27401389 TI - [Talented students from vulnerable contexts and their admission into Medical Schools]. PMID- 27401390 TI - [An unusual case of rupture of a nonaneurysmal aorta secondary to Salmonella aortitis]. PMID- 27401391 TI - [Why do pre graduate medical interns go into strike in Peru?]. PMID- 27401392 TI - [Effect of the -1639G > A polymorphism of the VKORC1 gene on the dose of oral anticoagulants acenocoumarol, and warfarin in Chilean patients: alternative models of inheritance]. PMID- 27401393 TI - [Not Available]. PMID- 27401394 TI - [Andropause and vulnerability in health: when do we start to educate men and health professionals?]. PMID- 27401395 TI - [Not Available]. PMID- 27401396 TI - Idiopathic ventricular arrhythmias: Relevance to the anatomy, diagnosis and treatment. AB - Idiopathic ventricular arrhythmias (VAs) are ventricular tachycardias (VTs) or premature ventricular contractions (PVCs) whose mechanisms are not related to myocardial scar. Idiopathic VAs occur most commonly without structural heart disease, but can occur with structural heart disease. Imaging tests, such as echocardiography, nuclear test, and cardiac magnetic resonance imaging, are helpful for excluding any association of an idiopathic VA occurrence with myocardial scar. Since catheter ablation emerged, the sites of idiopathic VA origins, commonly endocardial but sometimes epicardial, have been increasingly recognized. Idiopathic VAs usually originate from specific anatomical structures, and exhibit characteristic electrocardiograms based on their anatomical background. Idiopathic VAs are basically benign, but they require medical treatment or catheter ablation when idiopathic VAs are symptomatic, incessant, or produce left ventricular dysfunction. This review describes the up-to-date information on the prevalence of idiopathic VA origins relevant to the anatomy, and diagnosis, and treatment of idiopathic VAs. PMID- 27401397 TI - Down-regulation of renin-aldosterone and antidiuretic hormone systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome. AB - BACKGROUND: Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been postulated as the cause of chronic fatigue syndrome (CFS). A small heart or reduced left ventricular volume with reduced cardiac output has been reported to be common in patients with ME. The main circulatory blood volume regulators may be down-regulated. METHODS: Plasma levels of the neurohumoral factors that regulate circulatory blood volume were determined in 18 patients with ME and 15 healthy subjects (Controls). RESULTS: The echocardiographic examination revealed that the mean values for the left ventricular end-diastolic diameters, stroke volume index, and cardiac index as well as the mean blood pressure were all significantly smaller in the ME group than in the Controls. The mean plasma renin activity (1.6+/-1.0ng/ml/h vs. 2.5+/ 1.5ng/ml/h, p=0.06) was considerably lower in the ME group than in the Controls. Both the mean plasma aldosterone (104+/-37pg/ml vs. 157+/-67pg/ml, p=0.004) and antidiuretic hormone (ADH) (2.2+/-1.0pg/ml vs. 3.3+/-1.5pg/ml, p=0.02) concentrations were significantly lower in the ME group than in the Controls. Desmopressin (120MUg), a synthetic version of arginine vasopressin, was orally administered for five successive days to 10 patients with ME. In five patients (50%), the symptoms of orthostatic intolerance during a 10min active standing test were ameliorated in association with a significant increase in urinary osmotic pressure and decrease in heart rate. Furthermore, in five patients (50%), the performance status scores for the activities of daily living were improved. CONCLUSIONS: Both the renin-aldosterone and ADH systems were down-regulated despite the existence of reduction in cardiac preload and output in patients with ME. Desmopressin improved symptoms in half of the patients. PMID- 27401398 TI - Phosphorylated eEF2 is SUMOylated and induces cardiomyocyte apoptosis during myocardial ischemia reperfusion. AB - BACKGROUND: Cardiomyocyte apoptosis after myocardial ischemia reperfusion (MIR) blocks the recovery of cardiac function during revascularization treatment. Protein synthesis mediated by eukaryotic elongation factor 2 (eEF2) is vital for the recovery of MIR. eEF2 promotes peptide elongation without phosphorylation of itself. However, the exact function of eEF2 during MIR is unknown. METHODS: We used suture tie-down of left coronary artery (LCA) to induce MIR in vivo, which was confirmed by electrocardiography and Evan's blue/triphenyltetrazolium chloride double staining. Hypoxia/reoxygenation (H/R) treatment was utilized to stimulate H9c2 cells, which was detected by CCK8 assay to evaluate cell viability. eEF2, phosphorylated eEF2, SUMO, Bax, and Bcl-2 protein expressions and location of eEF2 and phosphorylated eEF2 were determined by western blot, immunocytochemistry and immunofluorescent staining. H9c2 cell apoptosis was assessed by flow cytometry. The effects of eEF2 full-length plasmid and its fragments on H9c2 cells were also detected. RESULTS: In vivo, phosphorylated eEF2 to eEF2 ratio decreased gently in rat MIR model. Immunocytochemistry showed that phosphorylated eEF2 translocated to the nucleus of cardiomyocytes during myocardial reperfusion. Furthermore, double immunofluorescent staining in H9c2 cells after H/R treatment also showed phosphorylated eEF2 translocated to the nucleus. Meanwhile, SUMOylation of eEF2 was detected. The overexpression of eEF2 upregulated Bcl-2 expression after H/R treatment, suggesting that eEF2 might reduce cardiomyocyte apoptosis during MIR. In addition, the N-terminal fragment of eEF2 transfection could promote apoptosis. CONCLUSIONS: eEF2 plays a bidirectional role in regulating cardiomyocyte apoptosis during MIR, in which eEF2 can be SUMOylated and translocate into nucleus of cardiomyocytes to promote cardiomyocyte apoptosis when eEF2 is phosphorylated. PMID- 27401399 TI - Mother-to-child transmission of hepatitis B: extent of knowledge of physicians and midwives in Eastern region of Ghana. AB - BACKGROUND: Mother -to -Child transmission of hepatitis B infection remains a major public health concern particularly in Africa. Adequate knowledge of physicians and midwives is crucial in averting most of the hepatitis B viral transmissions from mothers to their new-borns. However, there is a dearth of evidence on extent of knowledge of physicians and midwives in Ghana inspite of the increasing incidence of hepatitis B infection in the country. This study therefore assessed the knowledge level of physicians and midwives regarding Mother-to-Child transmission of hepatitis B in the Eastern region of Ghana. METHODS: A Cross sectional survey was conducted between August to November, 2015 using semi-structured self-administered questionnaire. Study participants were recruited from five health facilities and their level of awareness and knowledge about Mother-to-Child transmission of hepatitis B were assessed. The level of statistical significance was set at 0.05 alpha level. RESULTS: The findings showed that both physicians and midwives had good knowledge on Mother-to-Child transmission of hepatitis B infection. However, there were some knowledge gaps regarding effective hepatitis B prevention from mother to their newborns such as the use of hepatitis B vaccine and immunoglobulin. Additionally, 49.2 % (n = 62) of the participants had never attended any workshop on Mother-to-Child transmission of hepatitis B since completion of formal training. CONCLUSIONS: Developing appropriate periodic training programmes on current issues of hepatitis B for physicians and midwives in Eastern region will further enhance their knowledge. It is recommended that, further study examine if the knowledge of the respondents is translated into practice. PMID- 27401400 TI - Partial comparison of the NxTAG Respiratory Pathogen Panel Assay with the Luminex xTAG Respiratory Panel Fast Assay V2 and singleplex real-time polymerase chain reaction for detection of respiratory pathogens. AB - In this study, 185 nasopharyngeal swabs were tested to compare the sensitivity and specificity of the Luminex NxTAG (NxTAG) Respiratory Pathogen Panel (RPP) Assay with those of the Luminex Respiratory Virus Panel (RVP) Fast Assay v2 and singleplex real-time polymerase chain reaction (PCR). The NxTAG Assay identified at least one infectious agent in 164 (88.7%) of the swabs. In 91 (6.2%) tests with negative results with the RVP Fast Assay v2, a virus was identified by the NxTAG (P < 0.001). With the NxTAG Assay, the detection rates were significantly higher for respiratory syncytial virus (P = 0.003), human metapneumovirus (P < 0.001), human rhinovirus/human enterovirus (P = 0.009) and human adenovirus (P < 0.001). Finally, the NxTAG Assay identified M. pneumoniae in 32 of 44 (72.7%) PCR positive samples. However, the concordance with real-time PCR results was low for both assays. In conclusion, the results indicate that the NxTAG Assay overcomes some of the limitations of previous Luminex assays, although further studies are needed for a more complete evaluation of the new assay. PMID- 27401402 TI - Management of combined knee medial compartmental and patellofemoral osteoarthritis with lateral closing wedge osteotomy with anterior translation of the distal tibial fragment: Does the degree of anteriorization affect the functional outcome and posterior tibial slope? AB - BACKGROUND: The aim of this study was to assess the effect of degree of anterior translation of the distal tibial fragment after lateral closing wedge high tibial osteotomy in patients having combined knee medial compartmental and patellofemoral osteoarthritis. METHODS: A retrospective study was conducted on 64 patients who were operated on for combined knee medial compartmental and patellofemoral osteoarthritis, by lateral closing wedge high tibial osteotomy with anterior translation of the distal tibial fragment. They were divided into two groups; Group I comprising 32 patients (34 knees, mean age of 51.4+/-7years) whose degree of anterior translation was <1cm and Group II comprising 32 patients (33 knees, mean age of 52.2+/-8.3years) whose degree of anterior translation was >1.5cm. The final assessment was performed via: visual analog scale, postoperative Knee Society clinical rating system function score, active range of motion, time to union, degree of correction of mechanical axis, posterior tibial slope, and Insall-Salvati ratio. RESULTS: Group II patients exhibited statistically superior mean postoperative score and better return to their work than Group I (P=0.013, 0.076, respectively). Both groups showed statistically significant differences between the preoperative and postoperative evaluation parameters (P<0.001). The posterior tibial slope was decreased in both groups but with no significant difference (P=0.527). CONCLUSIONS: Lateral closing wedge high tibial osteotomy combined with anterior translation of the distal tibial fragment more than 1.5cm achieved significantly better postoperative functional knee score. Both groups exhibited comparatively decreased posterior tibial slope. PMID- 27401401 TI - Characterization of the Cytochrome P450 epoxyeicosanoid pathway in non-alcoholic steatohepatitis. AB - Non-alcoholic steatohepatitis (NASH) is an emerging public health problem without effective therapies. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into bioactive epoxyeicosatrienoic acids (EETs), which have potent anti inflammatory and protective effects. However, the functional relevance of the CYP epoxyeicosanoid metabolism pathway in the pathogenesis of NASH remains poorly understood. Our studies demonstrate that both mice with methionine-choline deficient (MCD) diet-induced NASH and humans with biopsy-confirmed NASH exhibited significantly higher free EET concentrations compared to healthy controls. Targeted disruption of Ephx2 (the gene encoding for soluble epoxide hydrolase) in mice further increased EET levels and significantly attenuated MCD diet-induced hepatic steatosis, inflammation and injury, as well as high fat diet-induced adipose tissue inflammation, systemic glucose intolerance and hepatic steatosis. Collectively, these findings suggest that dysregulation of the CYP epoxyeicosanoid pathway is a key pathological consequence of NASH in vivo, and promoting the anti-inflammatory and protective effects of EETs warrants further investigation as a novel therapeutic strategy for NASH. PMID- 27401403 TI - Metformin for chemo-radio-sensitization of NSCLC. PMID- 27401404 TI - A comparative planning study for lung SABR between tri-Co-60 magnetic resonance image guided radiation therapy system and volumetric modulated arc therapy. AB - BACKGROUND AND PURPOSE: To compare the plan quality of tri-(60)Co magnetic resonance image-guided radiation therapy (IGRT) to that of volumetric modulated arc therapy (VMAT) for lung stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: A total of 22 patients with lung tumors located in the lower lobe were selected retrospectively. For each patient, VMAT plans with linac and intensity-modulated radiation therapy (IMRT) plans with the tri-(60)Co system were generated with prescription doses of 60Gy (daily dose=15Gy). For both plan types, identical CT image sets and structures were used, with the exception of planning target volumes (PTV). The PTV for VMAT was generated from the internal target volume (ITV) while the PTV for the tri-(60)Co system was generated from the gross tumor volume (GTV). Clinically relevant dose-volumetric parameters were calculated and analyzed. RESULTS: The average PTV volumes of tri-(60)Co plans and VMAT plans were 10.5+/-12.3cc vs. 27.2+/-23.5cc, respectively (p<0.001). The maximum and mean doses to PTVs were 64.0+/-2.6Gy vs. 62.5+/-0.9Gy (p=0.005) and 61.4+/-1.7Gy vs. 60.0+/-0.5Gy (p<0.001), respectively. The conformity and homogeneity indices were 1.89+/-0.38 vs. 1.01+/-0.40 (p<0.001) and 0.06+/-0.02 vs. 0.04+/-0.00 (p<0.001), respectively. No considerable differences for organs at risk (OARs) were observed between tri-(60)Co plans and VMAT plans. In terms of target conformity, integral dose and lung mean dose, the plan quality of tri (60)Co plans was inferior to that of VMAT plans when the PTV volumes of tri (60)Co plans were less than 10cc. However, all treatment plans of tri-(60)Co system were clinically acceptable. CONCLUSION: For lung SABR, the quality of ITV based VMAT plans was better than that of GTV-based tri-(60)Co plans especially when the PTV volumes of the tri-(60)Co plans were less than 10cc. If the breathing pattern of a patient is reproducible, VMAT is considered the optimal option for lung SABR, otherwise the tri-(60)Co IGRT should be considered due to the ability to monitor tumor motion during treatment. PMID- 27401405 TI - Using implementation science to improve urologic oncology care. AB - There are many gaps between recommended urologic cancer care and real-world practice. Although we increasingly define these quality gaps because of our growing health services research capacity in urologic oncology, we often fall short in translating these findings into effective interventions and strategies to reduce gaps in care. In this article, we highlight implementation research as a logical next step for translating our health services research findings into effective individual and organizational behavior change strategies to improve quality of care. We explain how implementation research focuses on different, upstream outcomes from our clinical outcomes to get the right care to the right patient at the right time. Lastly, we share information about resources and training for those interested in learning more about this emerging, transdisciplinary field. PMID- 27401407 TI - Bioinspired Calcium Phosphate Nanoparticles Featuring as Efficient Carrier and Prompter for Macrophage Intervention in Experimental Leishmaniasis. AB - PURPOSE: To develop a biocompatible and bioresorbable calcium phosphate (CaP) nanoparticles (NPs) bearing Amphotericin B (AmB) with an aim to provide macrophage specific targeting in visceral leishmaniasis (VL). MATERIALS & METHODS: CaP-AmB-NPs were architectured through emulsion precipitation method. The developed formulation was extensively characterized for various parameters including in-vitro and in-vivo antileishmanial activity. Moreover, plasma pharmacokinetics, tissue biodistribution and toxicity profile were also assessed. RESULTS: Optimized CaP-AmB-NPs exhibited higher entrapment (71.1 +/- 6.68%) of AmB. No trend related to higher hemolysis was apparent in the developed formulation as evidenced in commercially available colloidal and liposomal formulations. Cellular uptake of the developed CaP-AmB-NPs was quantified through flow cytometry in J774A.1 cell line, and a 23.90 fold rise in uptake was observed. Fluorescent microscopy also confirmed the time dependent rise in uptake. In-vivo multiple dose toxicity study demonstrated no toxicity upto 5 mg/kg dose of AmB. Plasma kinetics and tissue distribution studies established significantly higher concentration of AmB in group treated with CaP-AmB-NPs in liver and spleen as compared to CAmB, LAmB and AmB suspension group. In-vivo animal experimental results revealed that the CaP-AmB-NPs showed higher splenic parasite inhibition compared to CAmB and LAmB in leishmania parasite infected hamsters. CONCLUSIONS: The investigated CaP-AmB-NPs are effective in provoking macrophage mediated uptake and collectively features lower toxicity and offers a suitable replacement for available AmB-formulations for the obliteration of intra macrophage VL parasite. PMID- 27401406 TI - Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor beta2 immunohistochemistry in prostate cancer. AB - BACKGROUND: Digital image analysis offers advantages over traditional pathologist visual scoring of immunohistochemistry, although few studies examining the correlation and reproducibility of these methods have been performed in prostate cancer. We evaluated the correlation between digital image analysis (continuous variable data) and pathologist visual scoring (quasi-continuous variable data), reproducibility of each method, and association of digital image analysis methods with outcomes using prostate cancer tissue microarrays (TMAs) stained for estrogen receptor-beta2 (ERbeta2). METHODS: Prostate cancer TMAs were digitized and evaluated by pathologist visual scoring versus digital image analysis for ERbeta2 staining within tumor epithelium. Two independent analysis runs were performed to evaluate reproducibility. Image analysis data were evaluated for associations with recurrence-free survival and disease specific survival following radical prostatectomy. RESULTS: We observed weak/moderate Spearman correlation between digital image analysis and pathologist visual scores of tumor nuclei (Analysis Run A: 0.42, Analysis Run B: 0.41), and moderate/strong correlation between digital image analysis and pathologist visual scores of tumor cytoplasm (Analysis Run A: 0.70, Analysis Run B: 0.69). For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99). Further, ERbeta2 staining was significantly associated with increased risk of prostate cancer-specific mortality (PCSM) when quantified by cytoplasmic digital image analysis (HR 2.16, 95 % CI 1.02-4.57, p = 0.045), nuclear image analysis (HR 2.67, 95 % CI 1.20-5.96, p = 0.016), and total malignant epithelial area analysis (HR 5.10, 95 % CI 1.70-15.34, p = 0.004). After adjusting for clinicopathologic factors, only total malignant epithelial area ERbeta2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012). CONCLUSIONS: Digital methods of immunohistochemical quantification are more reproducible than pathologist visual scoring in prostate cancer, suggesting that digital methods are preferable and especially warranted for studies involving large sample sizes. PMID- 27401408 TI - Large Size Microneedle Patch to Deliver Lidocaine through Skin. AB - PURPOSE: Current topical treatments using lidocaine (LD) for analgesia have limited applications due to their delayed analgesic actions, resulted from slow drug permeation through skin. The aim of this study is to fabricate a large size microneedle (MN) array patch containing LD, with fast onset of action, for the treatment of acute and chronic pain. METHODS: The MN patch was developed through photolithography and tested for its mechanical characteristics. In vitro and in vivo skin permeation, plasma pharmacokinetics, histology and skin irritation testing have also been performed for the MN patches. RESULTS: The MN have a mechanical strength of 10-30 N and more than 90% of the microneedles on the patch penetrated skin. It was shown that LD permeated through skin within 5 min of patch application. Subsequently, the in vivo skin permeation study using a porcine model showed that LD administrated by the MN patch was able to achieve the therapeutic level locally within 10 min and sustained for 8 h. It shows most of the drug diffuses perpendicularly against skin, with little lateral diffusion. After skin permeation LD remains within skin and unquantifiable amount of LD was found in the plasma of the pigs. Minor skin irritations were observed after 6 h of microneedle contact. However, the skin irritations resolved within 1 day following the removal of MN patch. CONCLUSION: The large size MN patches showed fast onset and sustained delivery of LD through skin, potentially useful to increase the application scope of topical LD for pain management. PMID- 27401409 TI - Development of a Novel Quantitative Structure-Activity Relationship Model to Accurately Predict Pulmonary Absorption and Replace Routine Use of the Isolated Perfused Respiring Rat Lung Model. AB - PURPOSE: We developed and tested a novel Quantitative Structure-Activity Relationship (QSAR) model to better understand the physicochemical drivers of pulmonary absorption, and to facilitate compound design through improved prediction of absorption. The model was tested using a large array of both existing and newly designed compounds. METHODS: Pulmonary absorption data was generated using the isolated perfused respiring rat lung (IPRLu) model for 82 drug discovery compounds and 17 marketed drugs. This dataset was used to build a novel QSAR model based on calculated physicochemical properties. A further 9 compounds were used to test the model's predictive capability. RESULTS: The QSAR model performed well on the 9 compounds in the "Test set" with a predicted versus observed correlation of R(2) = 0.85, and >65% of compounds correctly categorised. Calculated descriptors associated with permeability and hydrophobicity positively correlated with pulmonary absorption, whereas those associated with charge, ionisation and size negatively correlated. CONCLUSIONS: The novel QSAR model described here can replace routine generation of IPRLu model data for ranking and classifying compounds prior to synthesis. It will also provide scientists working in the field of inhaled drug discovery with a deeper understanding of the physicochemical drivers of pulmonary absorption based on a relevant respiratory compound dataset. PMID- 27401410 TI - Optimizing the Entrainment Geometry of a Dry Powder Inhaler: Methodology and Preliminary Results. AB - PURPOSE: For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of aerosol can be determined by the timing of dose emission into the tidal airstream. METHODS: An optimization algorithm was used to iteratively perform computational fluid dynamic (CFD) simulations of the drug emission of a DPI. The algorithm seeks to improve performance by changing the device geometry. Objectives were to achieve drug emission that was: A) independent of inhalation manoeuvre; B) similar to a target profile. The simulations used complete inhalation flow-rate profiles generated dependent on the device resistance. The CFD solver was OpenFOAM with drug/air flow simulated by the Eulerian-Eulerian method. RESULTS: To demonstrate the method, a 2D geometry was optimized for inhalation independence (comparing two breath profiles) and an early-bolus delivery. Entrainment was both shear-driven and gas-assisted. Optimization for a delay in the bolus delivery was not possible with the chosen geometry. CONCLUSIONS: Computational optimization of a DPI geometry for most similar drug delivery has been accomplished for an example entrainment geometry. PMID- 27401411 TI - A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma. AB - PURPOSE: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. METHODS: B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. RESULTS: B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. CONCLUSIONS: B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma. PMID- 27401412 TI - Human Immunodeficiency Virus (HIV) Separation and Enrichment via the Combination of Antiviral Lectin Recognition and a Thermoresponsive Reagent System. AB - PURPOSE: In order to improve the detection limit of existing HIV diagnostic assays, we explored the use of a temperature-responsive magnetic nanoparticle reagent system in conjunction with cyanovirin-N for HIV recognition to rapidly and efficiently concentrate viral particles from larger sample volumes, ~ 1 ml. METHODS: Cyanovirin-N (CVN) mutant, Q62C, was expressed, biotinylated, and then complexed with a thermally responsive polymer-streptavidin conjugate. Confirmation of protein expression/activity was performed using matrix assisted laser desorption/ionization (MALDI) and a TZM-bl HIV inhibition assay. Biotinylated CVN mutant recognition with gp120 was characterized using surface plasmon resonance (SPR). Virus separation and enrichment using a thermoresponsive magnetic nanoparticle reagent system were measured using RT-PCR. RESULTS: Biotinylated Q62C exhibited a KD of 0.6 nM to gp120. The temperature-responsive binary reagent system achieved a maximum viral capture of nearly 100% HIV, 1 * 10(5) virus copies in 100 MUl, using pNIPAAm-Q62C within 30 minutes. Additionally, the same reagent system achieved nearly 9-fold enrichment by processing a 10-times larger sample of 1000 MUl (Fig. 3). CONCLUSION: This work demonstrated a temperature-responsive reagent system that provides enrichment of HIV using antiviral lectin CVN for recognition, which is potentially amenable for use in point-of-care settings. PMID- 27401415 TI - Should Clinicians Recommend E-cigarettes to Their Patients Who Smoke? Yes. PMID- 27401413 TI - COMODI: an ontology to characterise differences in versions of computational models in biology. AB - BACKGROUND: Open model repositories provide ready-to-reuse computational models of biological systems. Models within those repositories evolve over time, leading to different model versions. Taken together, the underlying changes reflect a model's provenance and thus can give valuable insights into the studied biology. Currently, however, changes cannot be semantically interpreted. To improve this situation, we developed an ontology of terms describing changes in models. The ontology can be used by scientists and within software to characterise model updates at the level of single changes. When studying or reusing a model, these annotations help with determining the relevance of a change in a given context. METHODS: We manually studied changes in selected models from BioModels and the Physiome Model Repository. Using the BiVeS tool for difference detection, we then performed an automatic analysis of changes in all models published in these repositories. The resulting set of concepts led us to define candidate terms for the ontology. In a final step, we aggregated and classified these terms and built the first version of the ontology. RESULTS: We present COMODI, an ontology needed because COmputational MOdels DIffer. It empowers users and software to describe changes in a model on the semantic level. COMODI also enables software to implement user-specific filter options for the display of model changes. Finally, COMODI is a step towards predicting how a change in a model influences the simulation results. CONCLUSION: COMODI, coupled with our algorithm for difference detection, ensures the transparency of a model's evolution, and it enhances the traceability of updates and error corrections. COMODI is encoded in OWL. It is openly available at http://comodi.sems.uni-rostock.de/ . PMID- 27401416 TI - Should Clinicians Recommend E-cigarettes to Their Patients Who Smoke? No. PMID- 27401417 TI - Prevalence of Prediabetes and Abdominal Obesity Among Healthy-Weight Adults: 18 Year Trend. AB - PURPOSE: Trends in sedentary lifestyle may have influenced adult body composition and metabolic health among individuals at presumably healthy weights. This study examines the nationally representative prevalence of prediabetes and abdominal obesity among healthy-weight adults in 1988 through 2012. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES for the years 1999 to 2012, focusing on adults aged 20 years and older who have a body mass index (BMI) of 18.5 to 24.99 and do not have diabetes, either diagnosed or undiagnosed. We defined prediabetes using glycated hemoglobin (HbA1c) level ranges from 5.7% to 6.4%, as specified by the American Diabetes Association. Abdominal obesity was measured by waist circumference and waist-to height ratio. RESULTS: The prevalence of prediabetes among healthy-weight adults, aged 20 years and older and without diagnosed or undiagnosed diabetes, increased from 10.2% in 1988-1994 to 18.5% in 2012. Among individuals aged 45 years and older, the prevalence of prediabetes increased from 22.0% to 33.1%. The percentage of adults aged 20 years and older with an unhealthy waist circumference increased from 5.6% in 1988-1994 to 7.6% in 2012. The percentage of individuals with an unhealthy waist-to-height ratio increased from 27.2% in 1988 1994 to 33.7% in 2012. Adjusted models found that measures of abdominal obesity were not independent predictors of prediabetes among adults with a healthy BMI. CONCLUSIONS: Among individuals within a healthy BMI range, the prevalence of prediabetes and abdominal obesity has substantially increased. Abdominal obesity does not appear to be the primary cause of the increase. PMID- 27401418 TI - A Randomized Clinical Trial of a Tailored Lifestyle Intervention for Obese, Sedentary, Primary Care Patients. AB - PURPOSE: The aim of the study was to test a tailored lifestyle intervention for helping obese primary care patients achieve weight loss and increase physical activity. METHODS: We conducted a 24-month randomized clinical trial in Rhode Island. Primary care physicians identified obese, sedentary patients motivated to lose weight and increase their moderate to vigorous physical activity. These patients were randomized to 1 of 2 experimental groups: enhanced intervention (EI) or standard intervention (SI). Both groups received 3 face-to-face weight loss meetings. The enhanced intervention group also received telephone counseling calls, individually tailored print materials, and DVDs focused on diet and physical activity. Active intervention occurred in year 1 with a tapered maintenance phase in year 2. RESULTS: Two hundred eleven obese, sedentary patients were recruited from 24 primary care practices. Participants were 79% women and 16% minorities. They averaged 48.6 years of age, with a mean body mass index (BMI) of 37.8 kg/m(2), and 21.2 minutes/week of moderate to vigorous physical activity. Significantly more EI participants lost 5% of their baseline weight than SI participants (group by visit, P <.001). The difference was significant during active treatment at 6 months (37.2% EI vs 12.9% SI) and 12 months (47.8% vs 11.6%), but was no longer significant during the maintenance phase at 18 months (31.4% vs 26.7%,) or 24 months (33.3% vs 24.6%). The EI group reported significantly more minutes of moderate to vigorous physical activity over time than the SI group (group by visit, P = 0.04). The differences in minutes per week at 6 months was 95.7 for the EI group vs 68.3 minutes for the SI group; at 12 months, it was 126.1 vs 73.7; at 18 months, 103.7 vs 63.7, and at 24 months, 101.3 vs 75.4. Similar trends were found for absolute weight loss and the percentage reaching national guidelines for physical activity. CONCLUSION: A home based tailored lifestyle intervention in obese, sedentary primary care patients was effective in promoting weight loss and increasing moderate to vigorous physical activity, with the effects peaking at 12 months but waning at 24 months. PMID- 27401419 TI - Inadequate Hydration, BMI, and Obesity Among US Adults: NHANES 2009-2012. AB - PURPOSE: Improving hydration is a strategy commonly used by clinicians to prevent overeating with the goal of promoting a healthy weight among patients. The relationship between weight status and hydration, however, is unclear. Our objective was to assess the relationship between inadequate hydration and BMI and inadequate hydration and obesity among adults in the United States. METHODS: Our study used a nationally representative sample from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2012, and included adults aged 18 to 64 years. The primary outcome of interest was body mass index (BMI), measured in continuous values and also categorized as obese (BMI >=30) or not (BMI <30). Individuals with urine osmolality values of 800 mOsm/kg or greater were considered to be inadequately hydrated. Linear and logistic regressions were performed with continuous BMI and obesity status as the outcomes, respectively. Models were adjusted for known confounders including age, race/ethnicity, sex, and income-to-poverty ratio. RESULTS: In this nationally representative sample (n = 9,528; weighted n = 193.7 million), 50.8% were women, 64.5% were non-Hispanic white, and the mean age was 41 years. Mean urine osmolality was 631.4 mOsm/kg (SD = 236.2 mOsm/kg); 32.6% of the sample was inadequately hydrated. In adjusted models, adults who were inadequately hydrated had higher BMIs (1.32 kg/m(2); 95% CI, 0.85-1.79; P <.001) and higher odds of being obese (OR = 1.59; 95% CI, 1.35 1.88; P <.001) compared with hydrated adults. CONCLUSION: We found a significant association between inadequate hydration and elevated BMI and inadequate hydration and obesity, even after controlling for confounders. This relationship has not previously been shown on a population level and suggests that water, an essential nutrient, may deserve greater focus in weight management research and clinical strategies. PMID- 27401420 TI - Improving the Diagnosis and Treatment of Urinary Tract Infection in Young Children in Primary Care: Results from the DUTY Prospective Diagnostic Cohort Study. AB - PURPOSE: Up to 50% of urinary tract infections (UTIs) in young children are missed in primary care. Urine culture is essential for diagnosis, but urine collection is often difficult. Our aim was to derive and internally validate a 2 step clinical rule using (1) symptoms and signs to select children for urine collection; and (2) symptoms, signs, and dipstick testing to guide antibiotic treatment. METHODS: We recruited acutely unwell children aged under 5 years from 233 primary care sites across England and Wales. Index tests were parent-reported symptoms, clinician-reported signs, urine dipstick results, and clinician opinion of UTI likelihood (clinical diagnosis before dipstick and culture). The reference standard was microbiologically confirmed UTI cultured from a clean-catch urine sample. We calculated sensitivity, specificity, and area under the receiver operator characteristic (AUROC) curve of coefficient-based (graded severity) and points-based (dichotomized) symptom/sign logistic regression models, and we then internally validated the AUROC using bootstrapping. RESULTS: Three thousand thirty-six children provided urine samples, and culture results were available for 2,740 (90%). Of these results, 60 (2.2%) were positive: the clinical diagnosis was 46.6% sensitive, with an AUROC of 0.77. Previous UTI, increasing pain/crying on passing urine, increasingly smelly urine, absence of severe cough, increasing clinician impression of severe illness, abdominal tenderness on examination, and normal findings on ear examination were associated with UTI. The validated coefficient- and points-based model AUROCs were 0.87 and 0.86, respectively, increasing to 0.90 and 0.90, respectively, by adding dipstick nitrites, leukocytes, and blood. CONCLUSIONS: A clinical rule based on symptoms and signs is superior to clinician diagnosis and performs well for identifying young children for noninvasive urine sampling. Dipstick results add further diagnostic value for empiric antibiotic treatment. PMID- 27401422 TI - When Do Primary Care Physicians Retire? Implications for Workforce Projections. AB - PURPOSE: Retirement of primary care physicians is a matter of increasing concern in light of physician shortages. The joint purposes of this investigation were to identify the ages when the majority of primary care physicians retire and to compare this with the retirement ages of practitioners in other specialties. METHODS: This descriptive study was based on AMA Physician Masterfile data from the most recent 5 years (2010-2014). We also compared 2008 Masterfile data with data from the National Plan and Provider Enumeration System to calculate an adjustment for upward bias in retirement ages when using the Masterfile alone. The main analysis defined retirement as leaving clinical practice. The primary outcome was construction of a retirement curve. Secondary outcomes involved comparisons of retirement interquartile ranges (IQRs) by sex and practice location across specialties. RESULTS: The 2014 Masterfile included 77,987 clinically active primary care physicians between ages 55 and 80 years. The median age of retirement from clinical activity of all primary care physicians who retired in the period from 2010 to 2014 was 64.9 years, (IQR, 61.4-68.3); the median age of retirement from any activity was 66.1 years (IQR, 62.6-69.5). However measured, retirement ages were generally similar across primary care specialties. Females had a median retirement about 1 year earlier than males. There were no substantive differences in retirement ages between rural and urban primary care physicians. CONCLUSIONS: Primary care physicians in our data tended to retire in their mid-60s. Relatively small differences across sex, practice location, and time suggest that changes in the composition of the primary care workforce will not have a remarkable impact on overall retirement rates in the near future. PMID- 27401421 TI - A High Sense of Coherence as Protection Against Adverse Health Outcomes in Patients Aged 80 Years and Older. AB - PURPOSE: We set out to assess whether a high sense of coherence (SOC) protects from adverse health outcomes in patients aged 80 years and older who have multiple chronic diseases. METHODS: A population-based prospective cohort study in 29 primary care practices throughout Belgium included 567 individuals aged 80 years and older. We plotted the highest tertile of SOC scores in Kaplan-Meier curves representing 3-year mortality and time to first hospitalization. Using Cox proportional hazard regression analyses and multiple logistic regression analyses adjusted for sociodemographic characteristics, depression, cognition, disability, and multimorbidity we examined the relationship between SOC and mortality, hospitalization, and decline in performance of activities of daily living (ADL). RESULTS: Subjects with high SOC scores showed a higher cumulative survival than others (Log rank = 0.004) independent of other prognostic characteristics (adjusted hazard ratio 0.62 (95% CI, 0.38-1.00), P = .049). For ADL decline, a high SOC was shown to be protective, and this effect tended to be independent from the covariates under study (adjusted odds ratio 0.56 (95% CI, 0.31-1.0), P = .05). CONCLUSION: Even very elderly persons with high SOC scores were shown to have lower mortality rates and less functional decline. These effects were independent of multimorbidity, depression, cognition, disability, and sociodemographic characteristics. PMID- 27401423 TI - Interconception Care for Mothers During Well-Child Visits With Family Physicians: An IMPLICIT Network Study. AB - PURPOSE: Interconception care (ICC) is recommended to improve birth outcomes by targeting maternal risk factors, but little is known about its implementation. We evaluated the frequency and nature of ICC delivered to mothers at well-child visits and maternal receptivity to these practices. METHODS: We surveyed a convenience sample of mothers accompanying their child to well-child visits at family medicine academic practices in the IMPLICIT (Interventions to Minimize Preterm and Low Birth Weight Infants Through Continuous Improvement Techniques) Network. Health history, behaviors, and the frequency of the child's physician addressing maternal depression, tobacco use, family planning, and folic acid supplementation were assessed, along with maternal receptivity to advice. RESULTS: Three-quarters of the 658 respondents shared a medical home with their child. Overall, 17% of respondents reported a previous preterm birth, 19% reported a history of depression, 25% were smoking, 26% were not using contraception, and 58% were not taking folic acid. Regarding advice, 80% of mothers who smoked were counseled to quit, 59% reported depression screening, 71% discussed contraception, and 44% discussed folic acid. Screening for depression and family planning was more likely when the mother and child shared a medical home (P <.05). Most mothers, nearly 95%, were willing to accept health advice from their child's physician regardless of whether a medical home was shared (P >.05). CONCLUSIONS: Family physicians provide key elements of ICC at well-child visits, and mothers are highly receptive to advice from their child's physician even if they receive primary care elsewhere. Routine integration of ICC at these visits may provide an opportunity to reduce maternal risk factors for adverse subsequent birth outcomes. PMID- 27401424 TI - Seasonality of Ankle Swelling: Population Symptom Reporting Using Google Trends. AB - In our experience, complaints of ankle swelling are more common in summer, typically from patients with no obvious cardiovascular disease. Surprisingly, this observation has never been reported. To objectively establish this phenomenon, we sought evidence of seasonality in the public's Internet searches for ankle swelling. Our data, obtained from Google Trends, consisted of all related Google searches in the United States from January 4, 2004, to January 26, 2016. Consistent with our expectations and confirmed by similar data for Australia, Internet searches for information on ankle swelling are highly seasonal (highest in midsummer), with seasonality explaining 86% of search volume variability. PMID- 27401425 TI - Using Best-Worst Scaling to Understand Patient Priorities: A Case Example of Papanicolaou Tests for Homeless Women. AB - PURPOSE: Best-worst scaling (BWS) is a survey method for assessing individuals' priorities. It identifies the extremes-best and worst items, most and least important factors, biggest and smallest influences-among sets. In this article, we demonstrate an application of BWS in a primary care setting to illustrate its use in identifying patient priorities for services. METHODS: We conducted a BWS survey in 2014 in Boston, Massachusetts, to assess the relative importance of 10 previously identified attributes of Papanicolaou (Pap) testing services among women experiencing homelessness. Women were asked to evaluate 11 sets of 5 attributes of Pap services, and identify which attribute among each set would have the biggest and smallest influence on promoting uptake. We show how frequency analysis can be used to analyze results. RESULTS: In all, 165 women participated, a response rate of 72%. We identified the most and least salient influences on encouraging Pap screening based on their frequency of report among our sample, with possible standardized scores ranging from+1.0 (biggest influence) to -1.0 (smallest influence). Most important was the availability of support for issues beyond health (+0.39), while least important was the availability of accommodations for personal hygiene (-0.27). CONCLUSIONS: BWS quantifies patient priorities in a manner that is transparent and accessible. It is easily comprehendible by patients and relatively easy to administer. Our application illustrates its use in a vulnerable population, showing that factors beyond those typically provided in health care settings are highly important to women in seeking Pap screening. This approach can be applied to other health care services where prioritization is helpful to guide decisions. PMID- 27401426 TI - Comparison of the Male Osteoporosis Risk Estimation Score (MORES) With FRAX in Identifying Men at Risk for Osteoporosis. AB - PURPOSE: We wanted to compare the male osteoporosis risk estimation score (MORES) with the fracture risk assessment tool (FRAX) in screening men for osteoporosis. METHODS: This study reports analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the US population, comparing the operating characteristics of FRAX and MORES to identify men at risk for osteoporosis using a subset of 1,498 men, aged 50 years and older, with a valid dual-energy x-ray absorptiometry (DXA) scan. DXA-derived bone mineral density using a T score of -2.5 or lower at either the femoral neck or total hip defined the diagnosis of osteoporosis. Outcomes included the operating characteristics, area under the receiver-operator characteristic curve, and agreement of the FRAX and MORES. RESULTS: Sixty-seven (4.5%) of the 1,498 men had osteoporosis of the hip. The sensitivity, specificity, and area under the curve (AUC) for the MORES were 0.96 (95% CI, 0.87-0.99), 0.61 (95% CI, 0.58 0.63), and 0.87 (95% CI, 0.84-0.91), respectively. The sensitivity, specificity, and AUC for the FRAX were 0.39 (95% CI, 0.27-0.51), 0.89 (95% CI, 0.88-0.91), and 0.79 (95% CI, 0.75-0.84) respectively. Agreement was poor. CONCLUSIONS: Compared with the MORES, the FRAX underperformed as a screening strategy for osteoporosis using the threshold score suggested by the US Preventive Services Task Force (USPSTF). An integrated approach that uses the MORES to determine which men should have a DXA scan and the FRAX to guide treatment decisions, based on the risk of a future fracture, identified 82% of men who were candidates for treatments based on National Osteoporosis Foundation guidelines. PMID- 27401428 TI - The Critical Role of Clerks in the Patient-Centered Medical Home. AB - Research evaluating the effectiveness, function, and implementation of patient centered medical homes (PCMHs) has found major socioprofessional transformations and contributions of primary care physicians and, to a lesser degree, nurses. Our longitudinal ethnographic research with teams implementing PCMH in Veterans Health Administration (VHA) primary care identifies the important but largely underutilized contributions of clerks to PCMH outcomes. Although the relationship of high-performing clerical staff to patient satisfaction is widely acknowledged, PCMH can be further enhanced by enabling clerks to use administrative tasks as conduits for investing in long-term personalized relationships with patients that foster trust in the PCMH and the broader health care organization. Such relationships are engendered through the care-coordination activities clerks perform, which may be bolstered by organizational investment in clerks as skilled health care team members. PMID- 27401427 TI - Concept Mapping as a Method to Engage Patients in Clinical Quality Improvement. AB - Patient engagement has become a primary care research and practice priority. Little guidance exists, however, on how best to engage patients in primary care practice improvement, or how to measure the impact of their engagement. We present an overview of group concept mapping as a method for engaging patients in primary care practice improvement. We detail the group concept mapping process as a tool for use in primary care practice improvement, research, and evaluation, and we present resources to enable researchers and practice leaders to use this tool in practice improvement. To illustrate the method, we present a practice based quality improvement project conducted with patients and staff at a large urban academic primary care practice. PMID- 27401429 TI - A Dance With Mrs Chan. AB - As a third-year medical student on an internal medical clerkship, I learned the most important lesson about how to care for patients. I saw my attending physician give attention first to the person he was treating, and then to the patient and her clinical picture. They are not the same, and our training in medical school does not always teach us this distinction. Months later I found myself with an opportunity to truly help another individual who had been clinically and emotionally overcome by his disease. My attending physician's lesson guided me in a very meaningful way: it allowed me to remind a man that he was more than the disease he was fighting. Many times, it may be something very little that we need to do or say but to our patients, these little things end up being the biggest of them all. PMID- 27401436 TI - Erratum PMID- 27401437 TI - Meaning in Life in Earlier and Later Older-Adulthood: Confirmatory Factor Analysis and Correlates of the Meaning in Life Questionnaire. AB - OBJECTIVE: To validate the Meaning in Life Questionnaire (MLQ) in earlier and later older-adulthood, and examine its correlates. METHOD: Participants in earlier ( n = 341, M age = 68.5) and later older-adulthood ( n = 341, M age = 78.6) completed the MLQ and other measures. Confirmatory multigroup analysis, correlations, and regression models were conducted. RESULTS: A two-factor (presence and search), eight-item model of the MLQ had a good fit and was age invariant. Presence and search for meaning were largely unrelated. Meaning was associated with life satisfaction, well-being across a range of domains, and psychological resources. Searching for meaning correlated negatively with these variables, but to a lesser degree in later older-adulthood. DISCUSSION: The MLQ is valid in older-adulthood. Meaning in life is psychologically adaptive in older adulthood. Searching for meaning appears less important, especially in later older-adulthood. Findings are discussed in the context of aging and psychosocial development. PMID- 27401438 TI - Understanding Older Adult Use of Data Visualizations as a Resource for Maintaining Health and Wellness. AB - To better understand how older adults use health visualizations and the potential barriers that impact utility, we conducted semistructured interviews with 21 older adults. Within these sessions, we presented participants with two interactive visualizations for exploration. Through an affinity mapping exercise, we extracted five key themes associated with how older adults utilize health visualizations and provide corresponding recommendations as points of consideration for designers developing older adult focused health visualizations. By examining how older adults perceive the utility of health visualizations, we lay the groundwork for design choices that impact eventual use and adoption of systems that generate data for such visualizations. PMID- 27401439 TI - Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer. AB - Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996 2001. Individuals diagnosed with lung cancer (n = 920) and age- and sex-matched lung-cancer-free subjects (n = 1288) completed questionnaires documenting life time cigarette-smoking history and occupational, medical, and family history. Unweighted and weighted logistic models were fitted. Model overfitting was assessed using bootstrap-based cross-validation and 'shrinkage.' The discriminating ability was assessed by the c-statistic, and the risk-stratifying performance was assessed by examination of the variability in risk estimates over hypothetical risk-profiles. In the logistic models, the logarithm of incidence density of lung cancer was expressed as a function of age, sex, cigarette-smoking history, history of respiratory conditions and exposure to occupational carcinogens, and family history of lung cancer. The models entailed a minimal degree of overfitting ('shrinkage' factor: 0.97 for both unweighted and weighted models) and moderately high discriminating ability (c-statistic: 0.82 for the unweighted model and 0.66 for the weighted model). The method's risk-stratifying performance was quite high. The presented method allows for individualized assessment of risk of lung cancer and can be used for development of risk assessment models for other illnesses. PMID- 27401440 TI - Integrating eFAST in the initial management of stable trauma patients: the end of plain film radiography. AB - BACKGROUND: The initial management of a trauma patient is a critical and demanding period. The use of extended focused assessment sonography for trauma (eFAST) has become more prevalent in trauma rooms, raising questions about the real "added value" of chest X-rays (CXRs) and pelvic X-rays (PXR), particularly in haemodynamically stable trauma patients. The aim of this study was to evaluate the effectiveness of a management protocol integrating eFAST and excluding X-rays in stable trauma patients. METHODS: This was a prospective, interventional, single-centre study including all primary blunt trauma patients admitted to the trauma bay with a suspicion of severe trauma. All patients underwent physical examination and eFAST (assessing abdomen, pelvis, pericardium and pleura) before a whole-body CT scan (WBCT). Patients fulfilling all stability criteria at any time in transit from the scene of the accident to the hospital were managed in the trauma bay without chest and PXR. RESULTS: Amongst 430 patients, 148 fulfilled the stability criteria (stability criteria group) of which 122 (82 %) had no X-rays in the trauma bay. No diagnostic failure with an immediate clinical impact was identified in the stability criteria group (SC group). All cases of pneumothorax requiring chest drainage were identified by eFAST associated with a clinical examination before the WBCT scan in the SC group. The time spent in the trauma bay was significantly shorter for the SC group without X-rays compared to those who received any X-ray (25 [20; 35] vs. 38 [30; 60] min, respectively; p < 0.0001). An analysis of the cost and radiation exposure showed savings of 7000 ? and 100 mSv, respectively. CONCLUSIONS: No unrecognized diagnostic with a clinical impact due to the lack of CXR and PXR during the initial management of stable trauma patients was observed. The eFAST associated with physical examination provided the information necessary to safely complete the WBCT scan. It allowed a sensible cost and radiation saving. PMID- 27401441 TI - Toe-to-room temperature gradient correlates with tissue perfusion and predicts outcome in selected critically ill patients with severe infections. AB - BACKGROUND: Microcirculatory disorders leading to tissue hypoperfusion play a central role in the pathophysiology of organ failure in severe sepsis and septic shock. As microcirculatory disorders have been identified as strong predictive factors of unfavourable outcome, there is a need to develop accurate parameters at the bedside to evaluate tissue perfusion. We evaluated whether different body temperature gradients could relate to sepsis severity and could predict outcome in critically ill patients with severe sepsis and septic shock. METHOD: We conducted a prospective observational study in a tertiary teaching hospital in France. During a 10-month period, all consecutive adult patients with severe sepsis or septic shock who required ICU admission were included. Six hours after initial resuscitation (H6), we recorded the hemodynamic parameters and four temperature gradients: central-to-toe, central-to-knee, toe-to-room and knee-to room. RESULTS: We evaluated 40 patients with severe sepsis (40/103, 39 %) and 63 patients with septic shock (63/103, 61 %). In patients with septic shock, central to-toe temperature gradient was significantly higher (12.5 [9.2; 13.8] vs 6.9 [3.4; 12.0] degrees C, P < 0.001) and toe-to-room temperature gradient significantly lower (1.2 [-0.3; 5.2] vs 6.0 [0.6; 9.5] degrees C, P < 0.001) than in patients with severe sepsis. Overall ICU mortality rate due to multiple organ failure (MOF) was 21 %. After initial resuscitation, toe-to-room temperature gradient was significantly lower in patients dead from MOF than in the survivors (-0.2 [-1.1; +1.3] degrees C vs +3.9 [+0.5; +7.2] degrees C, P < 0.001) and the difference in gradients increased during the first 24 h. Furthermore, toe-to-room temperature gradient was related to tissue perfusion parameters such as arterial lactate level (r = -0.54, P < 0.0001), urine output (r = 0.37, P = 0.0002), knee capillary refill time (r = -0.42, P < 0.0001) and mottling score (P = 0.001). CONCLUSIONS: Toe-to-room temperature gradient reflects tissue perfusion at the bedside and is a strong prognosis factor in critically ill patients with severe infections. PMID- 27401442 TI - Lymph Node Ratio Analysis After Neoadjuvant Chemotherapy is Prognostic in Hormone Receptor-Positive and Triple-Negative Breast Cancer. AB - BACKGROUND: Lymph node ratios (LNR), the proportion of positive lymph nodes over the number excised, both defined as ranges and single ratio values are prognostic of outcome. Little is known of the prognostic value of LNR after neoadjuvant chemotherapy (NAC) according to molecular subtype. METHODS: From 2003 to 2014, patients who underwent definitive surgery after NAC were identified. LNR was calculated for node-positive patients who received axillary dissection or had at least 6 nodes removed. DFS was calculated using the Kaplan-Meier log rank test for yp N0-3 status, LNR categories (LNRC) <=0.20 (low), 0.21-0.65 (intermediate), >0.65 (high), and single LNR values. RESULTS: Of 428 NAC recipients, 263 were node negative and 165 (38.6 %) node positive: ypN1 = 97 (58.8 %), ypN2 = 43 (26.1 %), and ypN3 = 25 (15.2 %). Among node-positive cancers, the median number of LN removed was 14 (range, 6-51) and the median LNR was 0.22 (range, 0.03-1.0). Nodal stage was inversely associated with 5-year DFS: 91.5 % (ypN0), 74.5 % (ypN1), 49.8 % (ypN2), and 50.7 % (ypN3) (p < 0.001). LNRC was similarly inversely associated with DFS: 69.1 % (low), 71.4 % (intermediate), 49.3 % (high) (p < 0.001). Significant associations between LNRC and DFS were demonstrated in hormone receptor (HR)-positive and triple negative breast cancer (TNBC) subtypes, p = 0.02 and p = 0.003. A single-value LNR <= 0.15 in node-positive, HR-positive (94.1 vs 67.7 %; p = 0.04) and TNBC (94.1 vs 47.8 %; p = 0.001) groups was also significant. CONCLUSIONS: Residual nodal disease after NAC, analyzed by LNRC or LNR = 0.15 cutoff value, is prognostic and can discriminate between favorable and unfavorable outcomes for HR-positive and TNBC cancers. PMID- 27401443 TI - Feasibility of Laparoscopic Radical Gastrectomy for Gastric Cancer of Clinical Stage II or Higher: Early Outcomes in a Phase II Study (KUGC04). AB - PURPOSE: A phase II study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) for gastric cancer of clinical stage II or higher. METHODS: The eligibility criteria were gastric cancer of clinical stage II or higher that was amenable to potentially curative resection. Patients with prior chemotherapy, tumors requiring total gastrectomy (TG), tumors that invaded adjacent organs, and patients with bulky lymph node metastasis were included. The primary endpoint was incidence of postoperative complications of grade II or higher in the Clavien-Dindo classification. The sample size was determined to be 73, based on an expected rate of complications of 19 % and a threshold of 30 %. Gastrectomy was performed by expert surgeons who were certified by the Japan Society for Endoscopic Surgery. RESULTS: A total of 73 patients were enrolled; 54 patients (74 %) had clinical T stage T4a/T4b, and 47 patients (64 %) were administered preoperative chemotherapy. The type of surgery was distal gastrectomy in 41 patients and TG in 31 patients. Dissection of D2 or more was performed in 62 patients (85 %). Of the 25 patients who underwent D2/D2+ TG, 15 underwent splenectomy or pancreaticosplenectomy. R0 resection was performed in 64 patients (88 %). The median number of resected lymph nodes was 56, and postoperative complications occurred in 15 patients (20.5 %), which was significantly lower than the threshold value (p = 0.039). One in-hospital death occurred (1.4 %). CONCLUSION: LG for gastric cancer of clinical stage II or higher can be safely performed by experienced surgeons. PMID- 27401444 TI - Assessing, Counseling, and Treating Patients at High Risk for Breast Cancer. AB - Identifying patients at high risk of carrying pathogenic variants in genes is a crucial part of providing both accurate counseling and evidence-based treatment recommendations. Current risk assessment models have strengths and weaknesses that may limit their applicability to specific clinical circumstances. Clinicians must have knowledge regarding variations in available models, how they should be used, and what data they can expect from specific models. In addition, indications for genetic testing are expanding, and the adoption of next generation sequencing has allowed the creation of multigene testing panels. Complex consequences of panel testing have included an increase in the incidence of identifying variants of uncertain significance and the identification of pathogenic variants in genes for which treatment guidelines are not available. Women diagnosed with breast cancer who carry pathogenic variants in genes with proven associations with breast cancer (BRCA1/2) or highly likely associations (PTEN, PALB2) require additional risk assessment to facilitate treatment decisions that will limit in-breast tumor recurrence and contralateral breast cancer. PMID- 27401445 TI - Parenchyma-Sparing Hepatectomy with Vascular Reconstruction Techniques for Resection of Colorectal Liver Metastases with Major Vascular Invasion. AB - BACKGROUND: Resectability of colorectal liver metastasis (CRLM) depends on major vascular involvement and is affected by chemotherapy-induced liver injury. Parenchyma-sparing with combined resection and reconstruction of involved vessels may expand the indications and safety of hepatectomy. METHODS: Of 92 patients who underwent hepatectomy for CRLM, 15 underwent major vascular resection and reconstruction. The reconstructed vessels were the portal vein (PV) in five cases, the major hepatic vein (HV) in nine cases, and the inferior vena cava in six cases. RESULTS: All PV reconstructions were direct anastomoses. The HV was reconstructed with an autologous inferior mesenteric venous patch or an external iliac vein interposition graft. Total hepatic vascular exclusion was performed for six patients. Of nine patients with HV reconstruction, three had tumors involving all three major HVs, in whom the left HV was reconstructed as an only vein after extended right hepatectomy. In another six patients, multiple bilobar tumors or tumors in the liver that had chemotherapy-induced injury involved one or two HVs. Parenchyma-sparing by reconstruction of the HV was performed to secure the residual liver function. The patients with vascular reconstruction had an operative time of 462 +/- 111 min and a blood loss of 1278 +/- 528 mL. No complication classified as Clavien-Dindo 3 or more developed. The median hospital stay was 17 days (range 8-26 days). The cumulative 5-year survival rate for all the patients was 54.6 %, with no significant difference according to vascular reconstruction. CONCLUSION: Parenchyma-sparing hepatectomy combined with vascular reconstruction is a useful option to avoid major hepatectomy among various procedures for resection of CRLM with major vascular invasion. PMID- 27401446 TI - Dense Breasts: What Do Our Patients Need to Be Told and Why? AB - More than 50 % of states have state-mandated density notification for patients with heterogeneously or extremely dense breasts. Increased breast density carries a risk of masking a cancer and delaying diagnosis. Supplemental imaging is optional and often recommended for certain patients. There are no evidence-based consensus guidelines for screening patients with density as their only risk factor. Breast cancer risk assessment and breast cancer prevention strategies should be discussed with women with dense breasts. PMID- 27401447 TI - Melanoma in Mexico: Clinicopathologic Features in a Population with Predominance of Acral Lentiginous Subtype. AB - BACKGROUND: The aim of this study was to analyze the clinicopathologic features of melanoma in Mexico as the demographics of melanoma are not well known in Mexican and Latin American people. MATERIALS AND METHODS: A total of 1219 patients with cutaneous melanoma were analyzed through a retrospective database collected from a cancer referral institute, and the results were compared with developed countries. RESULTS: Median age was 57 years, and 713 (58.5 %) were females. The most common melanoma subtype was acral lentiginous melanoma (ALM), which was observed in 538 (44.1 %) patients. Median Breslow thickness was 5.2 mm. Among 837 patients with complete data, the 5-year disease-specific survival (DSS) was 52.3 %. Factors associated with worse DSS on univariate analysis were Breslow thickness (p < 0.001), recurrence (p < 0.001), ulceration (p < 0.001), positive margin (p < 0.001), ALM (p = 0.001), and male sex (p = 0.001). Multivariate analysis demonstrated Breslow thickness [hazard ratio (HR) 1.45, 95 % confidence interval (CI) 1.27-1.65; p < 0.001], positive margin (HR 1.25, 95 % CI 1.03-1.57; p = 0.018), recurrence (HR 9.56, 95 % CI 6.89-9.87; p = 0.002), ALM (HR 8.07, 95 % CI 6.77-8.95; p = 0.004), and male sex (HR 1.33, 95 % CI 1.06-1.68; p = 0.013) as independent risk factors for DSS. CONCLUSION: Our patients had worse prognosis compared with data from the US Surveillance, Epidemiology, and End Results database. We found male sex and ALM as independent risk factors for worse survival, in addition to known risk factors. PMID- 27401448 TI - Curative Surgical Resection as a Component of Multimodality Therapy for Peritoneal Metastases from Goblet Cell Carcinoids. AB - BACKGROUND: The impact of histopathologic features on oncologic outcomes for patients with peritoneal metastases from goblet cell carcinoid (GCC) undergoing multimodality therapy, including cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), is unknown. METHODS: This study prospectively analyzed 43 patients with GCC undergoing CRS-HIPEC between 2005 and 2013. Pathology slides were re-reviewed to classify GCC into histologic subtypes according to the Tang classification. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: The 43 patients in this study underwent 50 CRS-HIPEC procedures for peritoneal metastases from GCC, and the majority received neoadjuvant and/or adjuvant systemic chemotherapy. The GCC demonstrated an aggressive phenotype with frequent lymph node and peritoneal metastases without systemic dissemination. The majority of the patients had Tang B GCC. The estimated median overall survival times after surgery for the patients with Tang A, B, and C GCC were respectively 59, 22, and 13 months. In a multivariate Cox regression analysis, poor survival was associated with patients who had Tang B or C GCC, those undergoing incomplete macroscopic resection, and those with symptoms at the time of CRS-HIPEC. The patients with Tang A GCC demonstrated oncologic outcomes similar to those with intermediate-grade (American Joint Committee on Cancer [AJCC] grade 2) disseminated mucinous appendiceal neoplasms, whereas the patients with Tang B and C GCC demonstrated survival rates similar to or worse than those with high-grade (AJCC grade 3) disseminated mucinous appendiceal neoplasms. CONCLUSIONS: Tang classification is an independent prognostic factor for poor survival after multimodality therapy for GCC. Patients with Tang C GCC demonstrate limited survival and are not ideal candidates for a surgical approach. PMID- 27401450 TI - Comparison of 1800 Robotic and Open Partial Nephrectomies for Renal Tumors. PMID- 27401449 TI - Statistical Report of Central Nervous System Tumors Histologically Diagnosed in the Sichuan Province of China from 2008 to 2013: A West China Glioma Center Report. AB - BACKGROUND: Sichuan is a province in the west of China with a population of 81.4 million. This is the first statistical report of central nervous system (CNS) tumors surgically treated and histologically diagnosed in a large Chinese population. METHODS: All the patient data were obtained from 86 medical facilities, which covered the Sichuan province population. Data from patients who underwent surgery between 2008 and 2013 and corresponding histology samples were re-reviewed in the major pathology centers. All the CNS tumors were categorized according to International Classification of Diseases (ICD)-10 and ICD-O-3 classifications and reviewed manually. The tumor distribution was analyzed and stratified by gender, age, race, and tumor sites. Tumors in some ethnic minorities, such as the Tibetan people, also were analyzed. RESULTS: The final analytic dataset included 35,496 records. The top four histologic tumors were meningioma (28.51 %), pituitary adenoma (15.00 %), nerve sheath (13.77 %), and glioblastoma (11.82 %). There was a dramatically high incidence of malignant tumor in males. The median age at diagnosis ranged from 13 years (pineal region tumors) to 56 years (metastatic brain tumors). Most of the tumors in the insular lobe or cerebellum were low grade, whereas those in the thalamus or basal ganglia were likely to be high grade. The incidence of malignant tumors or high-grade gliomas in the Tibetans was significantly lower than in the Chinese Han population. CONCLUSION: This report is a preliminary statistical analysis of brain and spinal tumors in a large Chinese population and may serve as a useful resource for clinicians, researchers, and patients' families. PMID- 27401451 TI - Combined delivery of temozolomide and the thymidine kinase gene for treatment of glioblastoma. AB - Glioblastoma is the most malignant form of brain tumor. In this study, combination therapy with temozolomide (TMZ) and the herpes simplex virus thymidine kinase (HSVtk) gene was evaluated in glioblastoma models. The R7L10 peptide was used as a carrier of TMZ and the HSVtk gene. TMZ was loaded into R7L10 micelles using the oil-in-water emulsion/solvent evaporation method. The TMZ-loaded R7L10 (R7L10-TMZ) micelles formed a complex with the HSVtk gene, pHSVtk. The formation of the R7L10-TMZ/pHSVtk complex was confirmed by gel retardation and heparin competition assays. An in vitro transfection assay demonstrated that the transfection efficiency of R7L10-TMZ was similar to that of R7L10 in C6 glioblastoma cells. R7L10-TMZ had greater anti-tumor effects than TMZ alone in C6 cells in vitro, suggesting that R7L10 is an efficient carrier of TMZ. The in vivo efficacy of the R7L10-TMZ/pHSVtk complex was evaluated in the intracranial glioblastoma model. HSVtk expression in tumors was confirmed by immunohistochemistry. Furthermore, a greater anti-tumor effect was observed in the R7L10-TMZ/pHSVtk group compared with the TMZ or R7L10/pHSVtk single injection group. In conclusion, combined delivery of TMZ and the HSVtk gene using R7L10 peptides may be useful for the treatment of glioblastoma. PMID- 27401452 TI - A rapid magnetic resonance acoustic radiation force imaging sequence for ultrasonic refocusing. AB - Magnetic resonance guided acoustic radiation force imaging (MR-ARFI) is being used to correct for aberrations induced by tissue heterogeneities when using high intensity focusing ultrasound (HIFU). A compromise between published MR-ARFI adaptive solutions is proposed to achieve efficient refocusing of the ultrasound beam in under 10 min. In addition, an ARFI sequence based on an EPI gradient echo sequence was used to simultaneously monitor displacement and temperature with a large SNR and low distortion. This study was conducted inside an Achieva 3T clinical MRI using a Philips Sonalleve MR-HIFU system to emit a 1 ms pulsed sonication with duty cycle of 2.3% at 300 Wac inside a polymer phantom. Virtual elements defined by a Hadamard array with sonication patterns composed of 6 phase steps were used to characterize 64 groups of 4 elements to find the optimal phase of the 256 elements of the transducer. The 384 sonication patterns were acquired in 580 s to identify the set of phases that maximize the displacement at the focal point. Three aberrators (neonatal skull, 8 year old skull and a checkered pattern) were added to each sonication pattern to evaluate the performance of this refocusing algorithm (n = 4). These aberrators reduced the relative intensities to 95.3%, 69.6% and 25.5% for the neonatal skull, 8 year old skull, and checkered pattern virtual aberrators respectively. Using a 10 min refocusing algorithm, relative intensities of 101.6%, 91.3% and 93.3% were obtained. Better relative intensities of 103.9%, 94.3% and 101% were achieved using a 25 min refocusing algorithm. An average temperature increase of 4.2 degrees C per refocusing test was induced for the 10 min refocusing algorithm, resulting in a negligible thermal dose of 2 EM. A rapid refocusing of the beam can be achieved while keeping thermal effects to a minimum. PMID- 27401453 TI - Effects of Bio-Oss(r) and Cerasorb(r) dental M on the expression of bone remodeling mediators in human monocytes. AB - In contribution to diverse techniques of bone reconstruction involving biomaterials in contemporary dentistry, this study aimed to evaluate the effect of the bone-grafting materials Bio-Oss(r) and Cerasorb(r) Dental M on the expression of cytokines associated with bone remodeling by human monocytes in vitro. Bio-Oss(r) and Cerasorb(r) Dental M were incubated in separate culture media, and their supernatants were added to mononuclear cells of human peripheral blood, some of which had been stimulated with Porphyromonas gingivalis. The frequency of total monocytes and CD14+ monocytes producing cytokines interleukin 6 (IL-6), IL-8, IL-10, IL-12, and tumor necrosis factor alpha (TNF-alpha) were determined by flow cytometry. One-way analysis of variance with repeated measures, followed by Tukey's post hoc test, revealed that stimulation with P. gingivalis increased the expression of IL-6 and IL-8 and reduced the expression of TNF-alpha compared to effects demonstrated in the control group (p < 0.05). Adding biomaterial supernatants did not significantly affect the expression of any cytokine evaluated, however, either in the absence or in the presence of bacterial stimulation. Our data suggest that Bio-Oss(r) and Cerasorb(r) Dental M neither stimulate cytokine production in human monocytes nor interfere with mechanisms of cell communication mediated by cytokines evaluated during stimulation with P. gingivalis. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2066-2073, 2017. PMID- 27401454 TI - Combination of transcriptomic and proteomic approaches helps to unravel the protein composition of Chelidonium majus L. milky sap. AB - MAIN CONCLUSION: A novel annotated Chelidonium majus L. transcriptome database composed of 23,004 unique coding sequences allowed to significantly improve the sensitivity of proteomic C. majus assessments, which showed novel defense-related proteins characteristic to its latex. To date, the composition of Chelidonium majus L. milky sap and biosynthesis of its components are poorly characterized. We, therefore, performed de novo sequencing and assembly of C. majus transcriptome using Illumina technology. Approximately, 119 Mb of raw sequence data was obtained. Assembly resulted in 107,088 contigs, with N50 of 1913 bp and N90 of 450 bp. Among 34,965 unique coding sequences (CDS), 23,004 obtained CDS database served as a basis for further proteomic analyses. The database was then used for the identification of proteins from C. majus milky sap, and whole plant extracts analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) approach. Of about 334 different putative proteins were identified in C. majus milky sap and 1155 in C. majus whole plant extract. The quantitative comparative analysis confirmed that C. majus latex contains proteins connected with response to stress conditions and generation of precursor metabolites and energy. Notable proteins characteristic to latex include major latex protein (MLP, presumably belonging to Bet v1-like superfamily), polyphenol oxidase (PPO, which could be responsible for browning of the sap after exposure to air), and enzymes responsible for anthocyanidin, phenylpropanoid, and alkaloid biosynthesis. PMID- 27401455 TI - Pharmacophore development and screening for discovery of potential inhibitors of ADAMTS-4 for osteoarthritis therapy. AB - In the development of osteoarthritis, aggrecan degrades prior to cartilage destruction. Aggrecanase-1 (ADAMTS-4) is considered to be the major enzyme responsible for cleaving the Glu373-Ala374 bond in the interglobular domain of aggrecan in humans. Therefore, inhibitors of ADAMTS-4 have therapeutic potential in the treatment of osteoarthritis. In the present work, we developed a chemical feature based pharmacophore model of ADAMTS-4 inhibitors using the HipHop module within the Catalyst program package in order to elucidate the structure-activity relationship and to carry out in-silico screening. The Maybridge database was screened using Hypo1 as a 3D query, and the best-fit hits that followed Lipinski's rule of five were subsequently screened to select the compounds. The hit compounds were then docked into the active site of ADAMTS-4, and interactions were visualized to determine the potential lead molecules. After subjecting all of the hits to various screening and filtering processes, 13 compounds were finally evaluated for their in vitro inhibitory activities. This study resulted in the identification of two lead compounds with potent inhibitory effects on ADAMTS-4 activity, with IC50 values of 0.042 MUM and 0.028 MUM, respectively. These results provide insight into the pharmacophoric requirements for the development of more potent ADAMTS-4 inhibitors. Graphical Abstract The aggrecan degrading metalloprotease ADAMTS-4 has been identified as a novel therapeutic target for osteoarthritis. In this work, we used HipHop-based pharmacophore modeling and virtual screening of the Maybridge database to identify novel ADAMTS 4 inhibitors. These novel lead compounds act as potent and specific inhibitors for the ADAMTS-4 enzyme and could have therapeutic potential in the treatment of OA. PMID- 27401456 TI - The management of paediatric diaphyseal femoral fractures: a modern approach. AB - The definitive treatment of paediatric femoral diaphyseal fractures remains controversial. Modalities of treatment vary mostly according to age, with fracture pattern and site having a lesser impact. Current evidence is reflective of this variation with most evidence cited by the American Academy of Orthopedic Surgeons being level 4 or 5. The authors present a review of the most up-to-date evidence relating to the treatment of these fractures in each age group. In an attempt to clarify the current trends, we have produced an algorithm for decision making based on the experience from our own tertiary referral level 1 major trauma centre. PMID- 27401457 TI - Clinical relevance of peroxisome proliferator-activated receptor-gamma expression in myxoid liposarcoma. AB - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. PPARgamma is essential in adipocyte differentiation from precursor cells. Its antitumorigenic effects are reported in certain malignancies; however, its effects in liposarcoma are unclear. METHODS: We analyzed PPARgamma expression using immunohistochemistry (IHC) in 46 patients with myxoid liposarcoma [MLS; median age, 47 years (range, 14-90 years) and mean follow-up period, 91 months (range, 13-358 months)]. PPARgamma mRNA expression levels were measured by quantitative reverse transcription polymerase chain reaction. Further, we evaluated the correlation of PPARgamma expression with clinical outcomes. RESULTS: We found that the metastasis-free survival rate was significantly higher in lower PPARgamma expressers [34 patients with labeling index (LI) <50 %] than in higher expressers (12 patients with LI >=50 %; p = 0.01). Cox multivariate analysis revealed that a higher PPARgamma level was an independent predictor of metastasis (relative risk = 6.945, p = 0.026). Furthermore, using 28 fresh MLS specimens, we confirmed an increased PPARgamma mRNA expression level in the higher LI group (p = 0.001). CONCLUSIONS: In this study, higher PPARgamma expression in MLS was a risk factor associated with distant metastasis; therefore, it would be a novel prognostic marker for MLS. Further analyses will help to understand the correlation between PPARgamma expression and tumor malignancy in liposarcoma. PMID- 27401458 TI - Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice. AB - Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades-long half life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low-dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd-treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low-dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low-dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma. PMID- 27401459 TI - Long-term spinal cord stimulation modifies canine intrinsic cardiac neuronal properties and ganglionic transmission during high-frequency repetitive activation. AB - Long-term spinal cord stimulation (SCS) applied to cranial thoracic SC segments exerts antiarrhythmic and cardioprotective actions in the canine heart in situ. We hypothesized that remodeling of intrinsic cardiac neuronal and synaptic properties occur in canines subjected to long-term SCS, specifically that synaptic efficacy may be preferentially facilitated at high presynaptic nerve stimulation frequencies. Animals subjected to continuous SCS for 5-8 weeks (long term SCS: n = 17) or for 1 h (acute SCS: n = 4) were compared with corresponding control animals (long-term: n = 15, acute: n = 4). At termination, animals were anesthetized, the heart was excised and neurones from the right atrial ganglionated plexus were identified and studied in vitro using standard intracellular microelectrode technique. Main findings were as follows: (1) a significant reduction in whole cell membrane input resistance and acceleration of the course of AHP decay identified among phasic neurones from long-term SCS compared with controls, (2) significantly more robust synaptic transmission to rundown in long-term SCS during high-frequency (10-40 Hz) presynaptic nerve stimulation while recording from either phasic or accommodating postsynaptic neurones; this was associated with significantly greater posttrain excitatory postsynaptic potential (EPSP) numbers in long-term SCS than control, and (3) synaptic efficacy was significantly decreased by atropine in both groups. Such changes did not occur in acute SCS In conclusion, modification of intrinsic cardiac neuronal properties and facilitation of synaptic transmission at high stimulation frequency in long-term SCS could improve physiologically modulated vagal inputs to the heart. PMID- 27401460 TI - Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats. AB - Intrauterine growth restriction (IUGR) and maternal consumption of a high saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation. PMID- 27401461 TI - Lysophosphatidic acid does not cause blood/lymphatic vessel plasticity in the rat mesentery culture model. AB - Understanding the mechanisms behind endothelial cell identity is crucial for the goal of manipulating microvascular networks. Lysophosphatidic acid (LPA) and serum stimulation have been suggested to induce a lymphatic identity in blood endothelial cells in vitro. The objective of this study was to determine if LPA or serum induces blood-to-lymphatic vessel phenotypic transition in microvascular networks. The rat mesentery culture model was used to observe the effect of stimulation on blood and lymphatic microvascular networks ex vivo. Vascularized mesenteric tissues were harvested from adult Wistar rats and cultured with LPA or 10% serum for up to 5 days. Tissues were then immunolabeled with PECAM to identify blood vessels and LYVE-1 or Prox1 to identify lymphatic vessels. We show that while LPA caused capillary sprouting and increased vascular length density in adult microvascular networks, LPA did not cause a blood-to-lymphatic phenotypic transition. The results suggest that LPA is not sufficient to cause blood endothelial cells to adopt a lymphatic identity in adult microvascular networks. Similarly, serum stimulation caused robust angiogenesis and increased lymphatic/blood vessel connections, yet did not induce a blood-to-lymphatic phenotypic transition. Our study highlights an understudied area of lymphatic research and warrants future investigation into the mechanisms responsible for the maintenance of blood and lymphatic vessel identity. PMID- 27401462 TI - Posttranscriptional regulation of 14-3-3zeta by RNA-binding protein HuR modulating intestinal epithelial restitution after wounding. AB - The 14-3-3zeta is a member of the family of 14-3-3 proteins and participates in many aspects of cellular processes, but its regulation and involvement in gut mucosal homeostasis remain unknown. Here, we report that 14-3-3zeta expression is tightly regulated at the posttranscription level by RNA-binding protein HuR and plays an important role in early intestinal epithelial restitution after wounding. The 14-3-3zeta was highly expressed in the mucosa of gastrointestinal tract and in cultured intestinal epithelial cells (IECs). The 3' untranslated region (UTR) of the 14-3-3zeta mRNA was bound to HuR, and this association enhanced 14-3-3zeta translation without effect on its mRNA content. Conditional target deletion of HuR in IECs decreased the level of 14-3-3zeta protein in the intestinal mucosa. Silencing 14-3-3zeta by transfection with specific siRNA targeting the 14-3-3zeta mRNA suppressed intestinal epithelial restitution as indicated by a decrease in IEC migration after wounding, whereas ectopic overexpression of the wild-type 14-3-3zeta promoted cell migration. These results indicate that HuR induces 14-3-3zeta translation via interaction with its 3' UTR and that 14-3-3zeta is necessary for stimulation of IEC migration after wounding. PMID- 27401463 TI - Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies. AB - BACKGROUND: Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) is a rare subtype of RCC which is firstly described as a distinct entity in 2004 so that clinical characteristics of Xp11.2 RCC in different gender and age are unknown. The purpose of systematic review and meta analysis is to provide a comprehensive assessment on them. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies which evaluate the clinical characteristics of Xp11.2 RCC. The literature published between July 2004 and May 2014 was searched. RESULTS: A total of 15 studies with 147 participants were included. The meta-analysis demonstrated that number of patients of all age in female was higher than in male with pooled OR of 3.93(95 % CI = 1.66-9.34). However, incidence of distant metastases (OR = 0.34, 95 % CI = 0.12-1.57) and lymphatic metastases (OR = 0.51, 95 % CI = 0.14-1.91), tumor stage (OR = 0.85, 95 % CI = 0.34-2.15) and overall survival (OS) (OR = 0.46, 95 % CI = 0.05-4.34) between male and female were comparable. Incidence in female was higher than in male with pooled OR of 5.13(95 % CI = 1.67-15.72) in adults, while in children no gender-related predominance (OR = 1.19, 95 % CI = 0.38-3.72) was observed. In addition, incidence of distant metastases (OR = 1.00, 95 % CI = 0.13 7.84) and lymphatic metastases (OR = 1.00, 95 % CI = 0.07-13.67) and tumor stage (OR = 1.94, 95 % CI = 0.20-19.03) between children and adults were comparable. Survival curves presented comparable outcomes between male and female (P = 0.707) as well as between children and adults (P = 0.383). CONCLUSIONS: Female patients with Xp11.2 RCC in adults exhibit a high incidence compared to male, but not in children. Comparable clinical characteristics including incidence of distant and lymphatic metastases, tumor stage and prognosis is presented between male and female as well as between children and adults. PMID- 27401464 TI - Catastrophic health expenditure and impoverishment in Mongolia. AB - BACKGROUND: The social health insurance coverage is relatively high in Mongolia; however, escalation of out-of-pocket payments for health care, which reached 41 % of the total health expenditure in 2011, is a policy concern. The aim of this study is to analyse the incidence of catastrophic health expenditures and to measure the rate of impoverishment from health care payments under the social health insurance scheme in Mongolia. METHODS: We used the data from the Household Socio-Economic Survey 2012, conducted by the National Statistical Office of Mongolia. Catastrophic health expenditures are defined an excess of out-of-pocket payments for health care at the various thresholds for household total expenditure (capacity to pay). For an estimate of the impoverishment effect, the national and The Wold Bank poverty lines are used. RESULTS: About 5.5 % of total households suffered from catastrophic health expenditures, when the threshold is 10 % of the total household expenditure. At the threshold of 40 % of capacity to pay, 1.1 % of the total household incurred catastrophic health expenditures. About 20,000 people were forced into poverty due to paying for health care. CONCLUSIONS: Despite the high coverage of social health insurance, a significant proportion of the population incurred catastrophic health expenditures and was forced into poverty due to out-of-pocket payments for health care. PMID- 27401465 TI - US officials ban Theranos CEO from running laboratories for two years. PMID- 27401466 TI - [Differentiation of ocular hypertension]. AB - The term ocular hypertension has been used for more than 30 years. It is defined as an elevated intraocular pressure above the statistical norm without detectable optic nerve head or visual field damage. The number of patients with ocular hypertension in Germany is estimated to be approximately 3-5 million. Increased intraocular pressure is a risk factor for conversion to primary open-angle glaucoma. Most patients with ocular hypertension (and no risk factors) can be followed on a regular basis without any treatment. Each visit should include measurement of intraocular pressure, optic nerve head examination with a slit lamp, imaging and perimetric examinations. Currently known risk factors are high intraocular pressure, higher age, myopia, a thin cornea and darkly pigmented skin. If risk factors are present, antiglaucomatous therapy is indicated. PMID- 27401467 TI - [Cavernous sinus thrombosis as a rare cause of exophthalmos in childhood : A case report]. AB - Complications of acute bacterial sinusitis mostly occur in children and adolescents. In particular, intracranial spread of the infection can lead to severe even fatal courses of the disease. This article is a case report about a 13-year-old boy suffering from left-sided headache, meningismus and exophthalmos as presenting symptoms. Cranial magnetic resonance imaging (MRI) showed merely right-sided sphenoid sinusitis; however, the diffusion-weighted MRI sequence indicated a left-sided cavernous sinus thrombosis, which could be confirmed by computed tomography (CT) angiography. Cerebrospinal fluid diagnostics showed significant leukocytosis confirming secondary meningitis. Finally, exophthalmos was explained by parainfectious cavernous sinus thrombosis and periorbital edema. This case report highlights the importance of extended and specific diagnostic imaging in cases of clinically suspected complications in children and adolescents with sinusitis and the diagnostic significance of diffusion-weighted MRI. PMID- 27401468 TI - Editorial: Special issue on health behavior change support systems. PMID- 27401470 TI - Combination Assays and Molecular Docking can Identify Binding sites of Anti Microtubule Drugs on Plasmodium falciparum Tubulin. AB - BACKGROUND: Lead compounds that target tubulin are being developed as agents against the human malaria parasite, Plasmodium falciparum. It is important to define the binding sites of these molecules on the tubulin dimer: Taxol, Vinca domains or novel binding pockets; however, extraction of native parasite tubulin is difficult. OBJECTIVE: This report aims to develop assays that allow the rapid assessment of binding sites of compounds on the tubulin dimer. METHOD: We have developed a simple growth assay, using a combination of two anti-microtubule drugs that have overlapping binding sites, to study whether the two drugs act in synergistic, antagonistic or neutral manner. Additionally, Molecular docking was used to predict the binding sites of the drugs. RESULTS: The combination assay shows antagonistic interactions between drugs having overlapping binding sites. In contrast, drugs that do not bind to overlapping sites show no interactions or synergism in this combination assay. Molecular docking predictions show that indeed, drugs with antagonistic interactions in the growth assay do bind to overlapping sites. CONCLUSION: These two assays can be a simple preliminary screen for the binding sites of novel anti-tubulin compounds being developed for malaria therapeutics. PMID- 27401469 TI - Incidence of sudden cardiac death in adults with end-stage renal disease: a systematic review and meta-analysis. AB - BACKGROUND: Although sudden cardiac death (SCD) is recognized as a distinct cause of death in patients with end stage renal disease (ESRD), its incidence has not been well summarized. METHODS: We performed a systematic review and meta-analysis of the literature based on a protocol developed a priori. We searched MEDLINE and EMBASE (inception to March 2015) for randomized controlled trials and cohort studies reporting the incidence of SCD in adult patients with ESRD on hemodialysis or peritoneal dialysis. We collected data on number of SCD as well as the definition of SCD for each individual study. A random-effects model was used to summarize the incidence of SCD. We conducted subgroup analyses to explore sources of heterogeneity. RESULTS: Forty two studies (n = 80,382 patients) were included in the meta-analysis. The incidence of SCD among adults with ESRD ranged from 0.4 to 10.04 deaths per 100 person-years. The definitions and assessment of SCD varied across the included studies. There was evidence of significant heterogeneity (I(2) = 98; p < 0.001), which was not explained by subgroup analyses stratified by mean age, proportion of hypertensive or diabetic patients, follow-up time, study size, or type of cohort studied. CONCLUSION: Current estimates of the incidence of SCD among adults with ESRD vary widely. There is a need for further studies to more accurately estimate the incidence of SCD in patients with ESRD. PMID- 27401471 TI - Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma. AB - Sorafenib is the only drug that demonstrates a survival benefit for advanced hepatocellular carcinoma (HCC). However, the therapeutic effect of sorafenib is limited, so development of a more effective treatment method and second-line treatments is needed. Since the advent of sorafenib, clinical studies have been conducted with a variety of drugs and treatment methods, mainly with molecular targeted therapy, but almost all trials have ended in failure. The reasons for the difficulty in the development of a novel drug or treatment method include the diversity of mechanisms in the carcinogenesis and development of HCC, as well as the presence of background liver diseases such as chronic hepatitis and cirrhosis. Trials with immune-checkpoint inhibitors, which have an entirely different anti-tumor mechanism from that of molecular targeted drugs or cytotoxic drugs, have recently begun. Based on the results to date, clinical trials are now being conducted with enriched target subjects. In the future, providing more individualized treatment approaches for patients with advanced HCC will be essential. PMID- 27401472 TI - 'Time-shrinking perception' in the visual system: a psychophysical and high density ERP study. AB - 'Time-shrinking perception (TSP)' is a unique perceptual phenomenon in which the duration of two successive intervals (T1 and T2) marked by three auditory stimuli is perceived as equal even when they are physically different. This phenomenon provides a link between time and working memory; however, previous studies have mainly been performed on the auditory modality but not the visual modality. To clarify the neural mechanism of visual TSP, we performed a psychophysical experiment and recorded event-related potentials (ERPs) under different T1/T2 combinations. Three successive black/white sinusoidal gratings (30 ms duration) were presented to the participants. In the psychophysical experiment, either T1 or T2 was varied from 240 to 560 ms in 40-ms steps, while T2 or T1 was fixed at 400 ms. Participants judged whether T1 and T2 were equal or not by pressing a button. ERPs were recorded from 128 scalp electrodes, while T1 was varied from 240, 320, and 400 ms with the 400 ms T2 duration, and vice versa. Behavioral data showed asymmetrical assimilation: When -80 ms <= (T1 - T2) <= +120 ms, TSP was observed in the T1-varied condition. When -120 ms <= (T1 - T2) <= +80 ms, it was also observed in the T2-varied condition. These asymmetric time ranges in vision were different from those in the auditory modality. ERP data showed that contingent negative variation (CNV) appeared in the fronto-central region at around 300-500 ms during T2 presentation in the T1 < T2 condition. In the /240/400/ pattern, the CNV amplitude was decreased at around 350 ms. In contrast, P3 appeared at the parietal region about 450-650 ms after T2 in the T1 > T2 condition. In the /400/240/ pattern, P3 amplitude was greater than those of other temporal patterns. These neural responses corresponded to participants' perception that T1 and T2 were not equal. The neural responses in the fronto central region were involved with endogenous temporal attention for discrimination. Moreover, neural responses in the parietal region were engaged in exogenous temporal attention. Therefore, fronto-parietal neural responses underlie temporal perception in vision. PMID- 27401474 TI - Gaze shifts during dual-tasking stair descent. AB - To investigate the role of vision in stair locomotion, young adults descended a seven-step staircase during unrestricted walking (CONTROL), and while performing a concurrent visual reaction time (RT) task displayed on a monitor. The monitor was located at either 3.5 m (HIGH) or 0.5 m (LOW) above ground level at the end of the stairway, which either restricted (HIGH) or facilitated (LOW) the view of the stairs in the lower field of view as participants walked downstairs. Downward gaze shifts (recorded with an eye tracker) and gait speed were significantly reduced in HIGH and LOW compared with CONTROL. Gaze and locomotor behaviour were not different between HIGH and LOW. However, inter-individual variability increased in HIGH, in which participants combined different response characteristics including slower walking, handrail use, downward gaze, and/or increasing RTs. The fastest RTs occurred in the midsteps (non-transition steps). While gait and visual task performance were not statistically different prior to the top and bottom transition steps, gaze behaviour and RT were more variable prior to transition steps in HIGH. This study demonstrated that, in the presence of a visual task, people do not look down as often when walking downstairs and require minimum adjustments provided that the view of the stairs is available in the lower field of view. The middle of the stairs seems to require less from executive function, whereas visual attention appears a requirement to detect the last transition via gaze shifts or peripheral vision. PMID- 27401473 TI - Multisensory perceptual learning is dependent upon task difficulty. AB - There has been a growing interest in developing behavioral tasks to enhance temporal acuity as recent findings have demonstrated changes in temporal processing in a number of clinical conditions. Prior research has demonstrated that perceptual training can enhance temporal acuity both within and across different sensory modalities. Although certain forms of unisensory perceptual learning have been shown to be dependent upon task difficulty, this relationship has not been explored for multisensory learning. The present study sought to determine the effects of task difficulty on multisensory perceptual learning. Prior to and following a single training session, participants completed a simultaneity judgment (SJ) task, which required them to judge whether a visual stimulus (flash) and auditory stimulus (beep) presented in synchrony or at various stimulus onset asynchronies (SOAs) occurred synchronously or asynchronously. During the training session, participants completed the same SJ task but received feedback regarding the accuracy of their responses. Participants were randomly assigned to one of three levels of difficulty during training: easy, moderate, and hard, which were distinguished based on the SOAs used during training. We report that only the most difficult (i.e., hard) training protocol enhanced temporal acuity. We conclude that perceptual training protocols for enhancing multisensory temporal acuity may be optimized by employing audiovisual stimuli for which it is difficult to discriminate temporal synchrony from asynchrony. PMID- 27401475 TI - The effect of an interactive weekly mobile phone messaging on retention in prevention of mother to child transmission (PMTCT) of HIV program: study protocol for a randomized controlled trial (WELTEL PMTCT). AB - BACKGROUND: Improving retention in prevention of mother to child transmission (PMTCT) of HIV programs is critical to optimize maternal and infant health outcomes, especially now that lifelong treatment is immediate regardless of CD4 cell count). The WelTel strategy of using weekly short message service (SMS) to engage patients in care in Kenya, where mobile coverage even in poor areas is widespread has been shown to improve adherence to antiretroviral therapy (ART) and viral load suppression among those on ART. The aim of this study is to determine the effect of the WelTel SMS intervention compared to standard care on retention in PMTCT program in Kenya. METHODS: WelTel PMTCT is a four to seven centers, two-arm open randomized controlled trial (RCT) that will be conducted in urban and rural Kenya. Over 36 months, we plan to recruit 600 pregnant women at their first antenatal care visit and follow the mother-infant pair until they are discharged from the PMTCT program (when infant is aged 24 months). Participants will be randomly allocated to the intervention or control arm (standard care) at a 1:1 ratio. Intervention arm participants will receive an interactive weekly SMS 'How are you?' to which they are supposed to respond within 24 h. Depending on the response (ok, problem or no answer), a PMTCT nurse will follow-up and triage any problems that are identified. The primary outcome will be retention in care defined as the proportion of mother-infant pairs coming for infant HIV testing at 24 months from delivery. Secondary outcomes include a) adherence to WelTel; (b) adherence to antiretroviral medicine; (c) acceptance of WelTel and (d) cost effectiveness of the WelTel intervention. DISCUSSION: This trial will provide evidence on the effectiveness of mHealth for PMTCT retention. Trial results and the cost-effectiveness evaluation will be used to inform policy and potential scale-up of mHealth among mothers living with HIV. TRIAL REGISTRATION: ISRCTN98818734 ; registered on 9th December 2014. PMID- 27401476 TI - Phenotype, proliferation and apoptosis of B lymphocytes in hemodialysis patients treated with recombinant human erythropoietin. AB - One of the major causes of disorders of the immune response in patients undergoing hemodialysis (HD) is weaker activity of their helper T lymphocytes (Th cells), mainly reduced proliferative capacity associated with decreased expression of key surface antigens. Since cooperation between Th and B lymphocytes is essential for B cell function, changes in Th cell phenotype and ability to proliferate or produce cytokines could directly translate into an impaired humoral response. Therefore, we investigated the T cell-dependent activity of B cells in HD patients focusing mainly on their proliferative kinetics, susceptibility to apoptosis and the ability to produce antibodies. Since our previous studies have shown the beneficial effects of recombinant human erythropoietin (rhEPO) on T lymphocytes, we also investigated the in vivo and in vitro influence of rhEPO on B cells. Our results show that B lymphocytes of HD patients, especially of those who are not treated with rhEPO, have reduced proliferative capacity in vitro, reflected in low number of cell divisions, decreased percentage of proliferating cells and an increased susceptibility to apoptosis. They are also characterized by impaired ability to produce immunoglobulins. We have found no significant changes in the expression of key antigens of B lymphocytes with the exception of IL-10R. Furthermore, we demonstrated a time- and health status-dependent impact of rhEPO on patient's B cells. Our results show possible mechanisms responsible for the deficiency of humoral responses in HD patients which, at least partially, can be modulated through the supplementation with rhEPO. PMID- 27401477 TI - Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation. AB - Although recent cancer immunotherapy strategies, including immune-checkpoint blockade (i.e. blocking PD-1, PD-L1 or CTLA-4), have shown durable clinical effects in some (but not all) patients with various advanced cancers, further understanding of human immunopathology, particularly in tumor microenvironments, is essential to improve this type of therapy. The major hurdle for immunotherapy is the immunosuppression that is found in cancer patients. There are two types of immunosuppression: one is induced by gene alterations in cancer; the other is local adaptive immunosuppression, triggered by tumor-specific T cells in tumors. The former is caused by multiple mechanisms via various immunosuppressive molecules and via cells triggered by gene alterations, including activated oncogenes, in cancer cells. The various immunosuppressive mechanisms involve signaling cascades that vary among cancer types, subsets within cancer types and individual cancers. Therefore, personalized immune-interventions are necessary to appropriately target oncogene-induced signaling that modulates anti-cancer immune responses, on the basis of genetic and immunological analysis of each patient. Further understanding of human cancer immunopathology may lead to real improvement of current cancer immunotherapies. PMID- 27401479 TI - Fish and aquatic habitat conservation in South America. PMID- 27401478 TI - Identification of appropriate cone length to avoid positive cone margin in high grade cervical intraepithelial neoplasia. AB - OBJECTIVE: To identify key factors for predicting positive cone margin and appropriate cone length. METHODS: We retrospectively reviewed the margin status of patients who received conization with high grade cervical intraepithelial neoplasia, along with other factors such as patient age, parity, preoperative cytology, size of disease, type of transformation zone, and cone length from patient records. Cut-off value of cone length was analyzed in women younger than 40 years old because we design conization with minimum length especially for women who wish for future pregnancy. Cut-off value of cone length was defined as length corresponds to estimated probability of positive cone margin equal to 0.1 by logistic regression analysis with variables selected by stepwise methods. RESULTS: Among 300 patients, 75 patients had positive cone margin. Multivariable analysis revealed that squamous cell carcinoma at preoperative cytology (p=0.001), 2 or more quadrant disease (p=0.011), and shorter cone length (p<0.001) were risk factors for positive cone margin. Stepwise methods identified cone length and size of lesion as important variables. With this condition, cut off value of cone length was estimated as 15 mm in single quadrant disease and 20 mm in 2 or more quadrant disease, respectively. CONCLUSION: We identified the independent risk factors of positive cone margin and identified the cut-off value of cone length to avoid positive cone margin in women younger than 40 years old. Conization should be performed not only according to colposcopic findings including type of transformation zone but size of disease and cone length. PMID- 27401480 TI - Freshwater fish faunas, habitats and conservation challenges in the Caribbean river basins of north-western South America. AB - The remarkable fish diversity in the Caribbean rivers of north-western South America evolved under the influences of the dramatic environmental changes of neogene northern South America, including the Quechua Orogeny and Pleistocene climate oscillations. Although this region is not the richest in South America, endemism is very high. Fish assemblage structure is unique to each of the four aquatic systems identified (rivers, streams, floodplain lakes and reservoirs) and community dynamics are highly synchronized with the mono-modal or bi-modal flooding pulse of the rainy seasons. The highly seasonal multispecies fishery is based on migratory species. Freshwater fish conservation is a challenge for Colombian environmental institutions because the Caribbean trans-Andean basins are the focus of the economic development of Colombian society, so management measures must be directed to protect aquatic habitat and their connectivity. These two management strategies are the only way for helping fish species conservation and sustainable fisheries. PMID- 27401481 TI - Fish composition and species richness in eastern South American coastal lagoons: additional support for the freshwater ecoregions of the world. AB - The relationships between fish composition, connectivity and morphometry of 103 lagoons in nine freshwater ecoregions (FEOW) between 2.83 degrees S and 37.64 degrees S were evaluated in order to detect possible congruence between the gradient of species richness and similarities of assemblage composition. Most lagoons included in the study were <2 km(2) , with a maximum of 3975 km(2) in surface area. Combined surface area of all lagoons included in the study was 5411 km(2) . Number of species varied locally from one to 76. A multiple regression revealed that latitude, attributes of morphometry and connectivity, and sampling effort explained a large amount of variability in species richness. Lagoon area was a good predictor of species richness except in low latitude ecoregions, where lagoons are typically small-sized and not affected by marine immigrants, and where non-native fish species accounted for a significant portion of species richness. Relationships between species and area in small-sized lagoons (<2 km(2) ) is highly similar to the expected number in each ecoregion, with systems located between 18.27 degrees S and 30.15 degrees S attaining higher levels of species richness. Similarities in species composition within the primary, secondary and peripheral or marine divisions revealed strong continental biogeographic patterns only for species less tolerant or intolerant to salinity. Further support for the FEOW scheme in the eastern border of South America is therefore provided, and now includes ecotonal systems inhabited simultaneously by freshwater and marine species of fishes. PMID- 27401482 TI - Ovarian differentiation and development in cachara Pseudoplatystoma fasciatum. AB - One thousand five hundred cachara or tiger shovelnose catfish Pseudoplatystoma fasciatum, obtained from induced reproduction, were used to determine the onset of ovarian differentiation and development and to record the main characteristics of this process. Samples were collected from 0 to 240 days post-fertilization (dpf) and the results classified into stages I-XII. Ovarian formation was histologically detected for the first time when juveniles measured mean +/- s.d. 51.5 +/- 8.3 mm total length (LT ) at 39-45 dpf (stages I-V), with intense somatic cell proliferation originating in the ovarian cavity. Both LT and age of fish had a positive correlation (P < 0.001) with ovarian differentiation, but LT showed a greater correlation (r(2) = 0.95) than age (r(2) = 0.85), especially during the initial stages of development. From stages VI to VII, the ovarian cavity was enlarged and undifferentiated oogonia were present. At stage VIII, small projections formed in the ovarian stroma towards the ventral region of the gonad (future ovarian lamellae) and the basal membrane and differentiated oogonia nests could be seen. At stages IX and X, the germ cells entered meiosis and folliculogenesis was completed by stages XI and XII, which can be considered late in comparison to other Siluriformes. This study has demonstrated that ovarian differentiation in P. fasciatum begins with an intense proliferation of squamous epithelial cells (somatic cells) during the early stages of development and that sex inversion protocols could, thus, be applied successfully before this period. Furthermore, the results have demonstrated that both size and age can influence gonad differentiation and development in this species. PMID- 27401483 TI - Evidence for habitat-driven segregation of an estuarine fish assemblage. AB - This study examined the spatio-temporal variability in fish assemblage structure and composition following monthly sampling (August 2006 to July 2007). Three estuarine zones (upper, middle and lower) of the unvegetated intertidal and subtidal channel habitats located in the Marapanim Estuary were investigated. In each of these zones, salinity, organic matter and sediment types were measured to assess any correlation between habitat types and the fish fauna. A total of 41 496 fishes, belonging to 76 species and 29 families, was recorded. Recurring changes in both species composition and trophic structure were attributed to seasonal variations, while habitat type played a more permanent role in modifying the structure of fish assemblages. Zooplanktivores (e.g. Lycengraulis grossidens) and herbivores (e.g. Cetengraulis edentulus) used the intertidal habitat almost exclusively and were associated with salinity and substratum composition (gravel, silt and mud). In contrast, benthophages (e.g. Cathorops spixii) and benthophage ichthyophages (e.g. Cynoscion leiarchus) were primarily associated with the subtidal habitat throughout the estuary and were highly related to the presence of sandy substrata. This study highlighted the intricate roles that local factors (such as habitat connectivity) may have on the distribution of fishes at the assemblage level. As such, incorporating habitat sharing or segregation between species should be viewed as essential for any comparisons of estuaries over large geographic scales, and in particular for conservation planning and management measures. PMID- 27401484 TI - Spatial patterns of distribution and the influence of seasonal and abiotic factors on demersal ichthyofauna in an estuarine tropical bay. AB - This study focused on the influence of local-scale environmental factors on key metrics of fish community structure and function at Guanabara Bay, an estuarine system that differs from all other south-western Atlantic estuaries due to the influence of an annual low-intensity upwelling event during late spring and summer, between November and March, when a warm rainy climate prevails. The spatial patterns of the bottom temperature and salinity were more heterogeneous during the rainy season than the dry season, being linked to total precipitation and seasonal oceanographic events. The study identified 130 species and 45 families, placing Guanabara Bay as one of the most species-rich tropical estuarine ecosystems, far exceeding 22 other Brazilian estuaries. These results, in addition to characteristics such as a relatively well-preserved mangrove forest, high productivity and favourable conditions for the growth and reproduction of estuarine species, indicate that Guanabara Bay plays a central role in supporting large populations of fishes, including commercially important species. PMID- 27401485 TI - Fish species from a micro-tidal delta in the Caribbean Sea. AB - A total of 66 fish species belonging to 32 families were recorded between November 2012 and April 2014 in the southern arm of the delta to the Atrato River. Total length (LT ; range: 1.7-48 cm), total mass (MT ), LT and MT relationships (b values ranged from 1.8 to 3.7, mostly with negative allometric growth), and LT frequency (for 25 species) were estimated for freshwater, estuarine and marine species. LT and MT of Porichthys pauciradiatus and Membras argentea are given for the first time and maximum LT records for 14 species exceed those in the literature. PMID- 27401486 TI - Thiony Simon 1985-2016. PMID- 27401488 TI - Manifestations of systemic lupus erythematosus in female patients with polysomy X: Possible roles of chromosome X. AB - Clinical manifestations of systemic lupus erythematosus (SLE) in female patients with polysomy X have been less characterized as compared to those in male patients. Here, we describe a 28-year-old woman with trisomy X (47,XXX) who developed SLE. She had polyarthritis, hemolytic anemia, and was positive for anti nuclear and anti-dsDNA antibodies. We discuss the common SLE manifestations with female polysomy X and the possible link between the development of SLE and the presence of extra X-chromosomes. PMID- 27401487 TI - Characterization of layered chondrocyte sheets created in a co-culture system with synoviocytes in a hypoxic environment. AB - Endeavouring to repair and regenerate articular cartilage using cell sheets, we have previously established a co-culture system of chondrocytes and synoviocytes, and have reported the successful and rapid production of chondrocyte sheets. In the present study, to examine the effects of oxygen concentration on the chondrocyte sheets, we co-cultured human articular chondrocytes and human synoviocytes in 2%, 5% and 21% oxygen, and measured chondrocyte metabolic activity and proliferation activities under each condition for 14 days in culture. Layered chondrocyte sheets were also created under each condition and the proteoglycan (PG) level was compared with the gene expression of type I collagen (COL1), COL2, COL27, tissue metallopeptidase inhibitor 1 (TIMP1), fibronectin-1 (FN1), SRY-related HMG Box 9 (SOX9), aggrecan-1 (ACAN), integrin alpha10 (ITGalpha10), matrix metalloproteinase 3 (MMP3), MMP13 and a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS5). Compared with 5% and 21% oxygen, the 2% condition caused significantly greater cell metabolic activity and proliferation (p < 0.05). The 2% condition produced a 10% greater PG level compared with 21% oxygen (p < 0.05). All conditions increased the expression of chondrocyte-specific genes, such as COL2, and were associated with low expression levels of catabolic factors, such as MMP3 and MMP13. These observations indicated that the specificity of the chondrocyte sheets was maintained under all conditions. The culture times did not differ between the 5% and 21% conditions. Compared with 21% oxygen, layered chondrocyte sheets rich in extracellular matrix were created 2.85 days earlier in 2% oxygen, which is similar to the level found in deep cartilage. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401489 TI - Understanding the Life Histories of Pregnant-Involved Young Aboriginal Women With Substance Use Experiences in Three Canadian Cities. AB - Despite attention paid to substance use during pregnancy, understandings of young Aboriginal women's experiences based on their perspectives have been virtually absent in the published literature. This study's objective was to understand the life experiences of pregnant-involved young Aboriginal women with alcohol and drugs. Semi-structured interviews to gather life histories were conducted with 23 young Aboriginal women who had experiences with pregnancy, and alcohol and drug use. Transcribed interviews were analyzed for themes to describe the social and historical contexts of women's experiences and their self-representations. The findings detail women's strategies for survival, inner strength, and capacities for love, healing, and resilience. Themes included the following: intersectional identities, life histories of trauma (abuse, violence, and neglect; intergenerational trauma; separations and connections), the ever-presence of alcohol and drugs, and the highs and lows of pregnancy and mothering. The findings have implications for guiding policy and interventions for supporting women and their families. PMID- 27401490 TI - Provincial alcohol index and its relationship to alcohol-related harm in Thailand: implications for subnational alcohol policy development. AB - BACKGROUND: The Provincial Alcohol Index (PAI) is one of the efforts to develop a composite measurement to operationalize the situation of alcohol consumption and related risk behaviors. The index offers a means for national and subnational alcohol control committees to address alcohol-related problems in their responsible jurisdiction areas. The objective of this study is to assess the relationship between PAI scores and alcohol-related problems using Thailand as an example. METHODS: Cross-sectional analyses of PAI scores based on the 2007 National Cigarette Smoking and Alcohol Drinking Behavior Survey (CSAD) and the National Statistical Office data were conducted. CSAD data were collected from 168,285 Thai residents aged 15 years and above in 76 provinces of Thailand (population range 180,787 to 5,716,248). The PAI scores were generated using three different methods based on five indicators: 1) prevalence of adult (>=15 years) drinkers, 2) prevalence of underage drinkers, 3) proportion of regular drinkers, 4) proportion of binge drinkers and 5) proportion of drink-drivers. Alcohol-related injuries and violent events together with provincial level covariates (age, gender, income and region) were assessed. Correlational and linear regression analyses were performed to examine the relationship between PAI scores and alcohol-related problems. RESULTS: The PAI scores generated from the three methods were significantly correlated with one another (r > 0.7, p < 0.05) and significantly related to alcohol-related problems after adjusting for the provincial level covariates. Based on the normalized method, PAI scores had a significant and positive relationship with prevalence of alcohol-related injuries (beta = 562 cases per million population, p = 0.027) and violence (beta = 451 events per million population, p = 0.013). PAI scores were highest in the north and lowest in the south of the country. CONCLUSIONS: The findings of this study illustrate the relationship between the PAI and alcohol-related problems. The PAI scores can be used to benchmark the alcohol situation across jurisdiction areas. Future studies are suggested to develop a scale to measure subnational alcohol policy performances. PMID- 27401491 TI - Initial experience with percutaneous coronary sinus catheter placement in minimally invasive cardiac surgery in an academic center. AB - BACKGROUND: Placement of a percutaneous coronary sinus catheter (CSC) by an anesthesiologist for retrograde cardioplegia in minimally invasive cardiac surgery is relatively safe in experienced hands. However, the popularity of its placement remains limited to a small number of centers due to its perceived complexity and potential complications. METHODS: We retrospectively reviewed all cardiac cases performed by one surgeon between December 2009 and April 2012. The reviewed cases were divided into two groups: cardiac cases with percutaneous CSC placement (CSC group) and cardiac cases without placement (control group). Anesthesia preparation time (APT) was then compared between the CSC group and control group. In the CSC group, cases were further divided into two groups. One group contained cases with an APT of less than 90 min (success group) and the other contained cases with an APT greater than or equal to 90 min or cases with CSC placement failure (delay/failure group). Patients' characteristics, type of surgery, and transesophageal echocardiography (TEE) findings were compared between the two groups (success group vs. delay/failure group) to identify variables associated with prolongation of the APT or CSC placement failure. RESULTS: Percutaneous CSC placement was required in 83 cases (CSC group). The catheter was successfully placed in 74 of those cases. We experienced one complication, coronary sinus injury after multiple attempts at placing the catheter. The mean APT was 102 +/- 31 min in the CSC group (n = 81) and 42 +/- 15 min in the control group (n = 285). We could not identify any variables associated with prolongation of the APT or catheter placement failure. CONCLUSIONS: The success rate of the placement was 89.1 % in our academic center. On average, placing the CSC added approximately one additional hour to the APT. This time is not an accurate representation of true catheter placement time, as it included time for preparation of the CSC, TEE, and fluoroscopy. We experienced one documented complication (coronary sinus injury), which was immediately diagnosed by TEE and fluoroscopy in the operating room. No variables associated with prolongation of APT or CSC placement failure were identified. PMID- 27401492 TI - Enrolling and keeping participants in multiple sclerosis self-management interventions: a systematic review and meta-analysis. AB - OBJECTIVES: The objectives were to provide an estimate of expected enrolment and attrition rates based on published studies of existing self-management interventions for people with multiple sclerosis, and to identify contributing factors and impact on outcomes. REVIEW METHODS: A systematic literature search was conducted using Ovid MEDLINE, PsychINFO, EMBASE, AMED, CINAHL, OT Seeker, PubMed, and the Cochrane Database of Systematic Reviews databases. Controlled trials with or without randomization using either a between-group or within person design were included if they met specified criteria. A random-effect meta regression analysis was conducted to estimate the overall enrolment and attrition proportions, effect of person- and study-related factors, and impact on outcomes. RESULTS: A total of 48 studies, comprising 4446 persons were identified. The estimated enrolment rate was 50.3% (95% confidence interval (CI): 49.6 to 51.1) and the estimated attrition rates in the intervention and control groups were 16.8% (95% CI: 16.2 to 17.3) and 14.4% (95% CI: 13.8 to 14.9), respectively. The main reported reason for refusing to participate was lack of interest (70.6%), while the reported reasons for dropping out were mainly owing to medical issues (26.1%) and disliking the intervention (17.9%). Trial, programme, and patient related variables were found to influence the enrolment and/or attrition rates. Studies that had a 10% higher attrition rate had an effect size that was larger by 0.19 (95% CI: 0.17 to 0.24). CONCLUSION: Greater understanding of the factors associated with enrolment and attrition rates would help in planning and developing a more appealing self-management intervention that patients can easily accept and incorporate into their everyday lives. PMID- 27401494 TI - The Role of Intra-personal and Inter-personal Factors in Fear of Childbirth: A Preliminary Study. AB - Childbirth is a major life event, but for some women, the fear of childbirth goes beyond trepidation towards full-blown anxiety and panic, known as fear of childbirth (FOC) or tokophobia. In the present study the authors investigated and compared the intrapersonal and interpersonal factors that might be associated with FOC among women who previously gave birth (parous) and women who did not. A cross sectional survey was conducted among 529 women (parous women (n = 365) and women who had never given birth (n = 173). All participants completed self-report measures using an online survey system. The questionnaires assessed intrapersonal factors including attitudes toward pregnancy and birth, body image, self-esteem and life satisfaction as well as interpersonal factors namely relationship satisfaction. Multiple regression analyses revealed that among parous women age and attitudes toward pregnancy and birth, especially those that relate to body image and delivery were significantly associated with FOC. Among women who had never given birth, only attitudes toward pregnancy and birth, especially those that relate to body image, importance of pregnancy and delivery, and preference of caesarean section (CS), were significantly associated with FOC. In both groups, satisfaction with spousal relationship was not found to be associated with FOC. The results indicate that regarding FOC, intra-personal factors are more dominant than inter-personal factors. When assessing this medico psychological fear, cognitive aspects should also be addressed. PMID- 27401493 TI - Primary pleuropulmonary and mediastinal synovial sarcoma: a clinicopathologic and molecular study of 26 genetically confirmed cases in the largest institution of southwest China. AB - BACKGROUND: Primary pleuropulmonary and mediastinal synovial sarcomas (PPMSSs) are extremely rare. The authors present the largest series in an Asian population. METHODS: Between 2000 and 2015, 26 genetically confirmed PPMSSs were included. The clinicopathologic features of all of the cases were reviewed. Immunohistochemical staining was carried out using the following antibodies: TLE1, cytokeratin (AE1/AE3), EMA, CD99, Bcl-2, CK7, CD34, S-100 protein, and Ki 67. The chromosomal translocation t(X;18)(p11.2;q11.2) was detected by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). We compared the clinical, pathologic, immunohistochemical, and molecular features of this series with that of the previous series and soft tissue synovial sarcomas. RESULTS: This series included 17 males and nine females. The median age was 36.5 years (range, 16-72 years). The tumors involved the lung (76.9 %), pleura (15.4 %), and mediastinum (7.7 %). The median tumor size was 6 cm (range 2.3 ~ 24 cm). The majority of the tumors were well-circumscribed. The tumors were classified as monophasic (84.6 %), biphasic (3.8 %), and poorly differentiated (11.5 %) types. The tumors were graded as French Federation of Cancer Centers (FNCLCC) grade 2 (62.5 %) and FNCLCC 3 (37.5 %). Diffuse immunostaining for TLE1, BCL-2, and CD99 was identified in 91.7, 95.7, and 56.0 % of the tumors, respectively. Focal positivity was seen with EMA (84.6 %), CK7 (55.6 %), cytokeratin (AE1/AE3) (68.0 %), CD34 (5.0 %), and S-100 protein (21.7 %). A high Ki-67 index (>=10 %) was observed in 91.3 % of the tumors. The fusion transcripts included SS18-SSX1 (15/22, 68.2 %), SS18-SSX2 including variants (6/22, 27.3 %), and SS18-SSX4 (1/22, 4.5 %) fusions. The remaining four cases showed positivity for SS18 rearrangement by FISH. Surgical excision of tumors or lobectomy were performed in 20 patients, and seven of the patients underwent adjuvant therapy. Clinical follow-up was available in 73.1 % cases, with a median follow-up of 12.0 months. The median survival time was 14.5 months. Tumor resection (p = 0.024) and no residual tumor (p = 0.004) were associated with an improved overall survival time. CONCLUSIONS: PPMSS is a highly aggressive neoplasm. Extensive surgical resection of the tumor and more effective adjuvant therapy should be advocated. PPMSS must be differentiated from similar diseases. PMID- 27401495 TI - Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. AB - BACKGROUND: Intravenous immunoglobulin (IVIG) is recommended treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Recent studies have demonstrated that subcutaneous immunoglobulin (SCIG) is feasible, safe, and effective in both disorders. IVIG leads to transient hemolysis and, consequently, we hypothesized that frequent small doses of SCIG exerts less hemolytic activity than a few larger doses of IVIG. STUDY DESIGN AND METHODS: In an open-label study, 23 three patients treated with IVIG for CIDP or MMN were switched to SCIG at an equal dosage. IVIG was administered two to three times for 6 weeks. Two weeks after the last IVIG infusion at Week 8, SCIG was initiated with injections twice or thrice weekly until Week 20. Blood samples were drawn 2 weeks after IVIG at Weeks 2 and 8 and during SCIG at Weeks 14 and 20 determining hemoglobin (Hb) and hemolytic variables. RESULTS: Seventeen patients completed the study. At enrollment, the Hb level was 138 +/- 12 g/L, haptoglobin level was 1.4 +/- 0.5 g/L, reticulocyte count was 58.7 * 109 +/- 21.3 * 109 /L, and bilirubin level was 6.6 +/- 2.3 umol/L. The average of the two blood samples drawn at comparable intervals during IVIG and SCIG showed that Hb increased from 135 +/- 15 to 138 +/- 15 g/L (p = 0.03). During IVIG the hemolytic variables showed signs of mild hemolysis that improved during SCIG, haptoglobin increasing from 1.2 +/- 0.5 to 1.5 +/- 0.6 g/L (p = 0.002), reticulocytes decreasing from 71.9 * 109 +/- 35.8 * 109 to 54.5 * 109 +/- 16.3 * 109 /L (p = 0.02), and bilirubin decreasing from 7.3 +/- 2.8 to 5.8 +/- 1.8 umol/L (p = 0.001). CONCLUSION: A switch from IVIG to SCIG was associated with a slight increase of Hb levels and an improvement of laboratory variables related to hemolytic activity. PMID- 27401496 TI - Triatomine physiology in the context of trypanosome infection. AB - Triatomines are hematophagous insects that feed on the blood of vertebrates from different taxa, but can occasionally also take fluids from invertebrate hosts, including other insects. During the blood ingestion process, these insects can acquire diverse parasites that can later be transmitted to susceptible vertebrates if they complete their development inside bugs. Trypanosoma cruzi, the etiological agent of Chagas disease, and Trypanosoma rangeli are protozoan parasites transmitted by triatomines, the latter only transmitted by Rhodnius spp. The present work makes an extensive revision of studies evaluating triatomine-trypanosome interaction, with special focus on Rhodnius prolixus interacting with the two parasites. The sequences of events encompassing the development of these trypanosomes inside bugs and the consequent responses of insects to this infection, as well as many pathological effects produced by the parasites are discussed. PMID- 27401497 TI - Pediatric psychology: where it's been and where it's going. PMID- 27401498 TI - 'Nothing about us without us'. PMID- 27401500 TI - An experimental study: quantitatively evaluating the change of the content of collagen fibres in penis with two-dimensional ShearWaveTM Elastography. AB - The purpose of this study was to explore the value of two-dimensional ShearWaveTM Elastography (2D-SWE) on quantitatively evaluating the change of the content of collagen fibres in penis. Twenty male Sprague Dawley rats were divided into the pre-sexual maturity group (Group 1) and the sexual decline group (Group 2) according to age. The ultrafast ultrasound device Aixplorer(r) (SuperSonic Imagine, Aix-en-Provence, France) was used for 2D-SWE imaging of penis, and the measurement index was shear wave stiffness (SWS). The immunohistochemistry was used to analyse the content of collagen fibres in penis, and the measurement index was positive area percentage (PAP). The differences of SWS between the two groups and PAP between the two groups were analysed. SWS of Group 1 and Group 2 was 10.18 +/- 1.09 and 8.02 +/- 1.34 kPa, and SWS of Group 2 was significantly lower than Group 1 (p < .01). PAP of Group 1 and Group 2 was 4.83 +/- 3.61% and 16.41 +/- 10.02%, and PAP of Group 2 was significantly higher than Group 1 (p < .01). Our results indicate that when the content of collagen fibres changes, SWS of penis measured with 2D-SWE would change significantly as well. Two-dimensional SWE can be used to quantitatively evaluate the change of the content of collagen fibres in penis. PMID- 27401499 TI - The HCV care continuum among people who use drugs: protocol for a systematic review and meta-analysis. AB - INTRODUCTION: The diagnosis, management, and treatment for hepatitis C virus (HCV) infection (the "HCV care continuum") have improved in recent years. People who use drugs (PWUD) have a prevalence of HCV infection from 30 to 70 %, yet rates of testing, engagement in care, and treatment for HCV are disproportionately low compared to other populations. Delineating the progression of PWUD through the steps in the HCV care continuum in the USA is important in informing efforts to improve HCV outcomes among PWUD. METHODS/DESIGN: Scientific databases will be searched using a comprehensive automated search strategy; gray literature and reference lists will be manually searched. Eligible reports will provide original research data related to the HCV care continuum in the USA including proportions of PWUD engaging in the following discrete steps: screening/testing, engagement in care (including receiving an HCV clinical assessment), treatment initiation and completion, and rates of those with successful HCV treatment. A quality-rating tool will be developed to ascertain the level of bias (including selection bias) in each report, and a quality score will be assigned to each eligible report. A tool adapted from the Pragmatic Explanatory Continuum Indicator Summary-2 instrument will be developed to assess the extent to which an included report reflects an effectiveness or efficacy study design. Pooled estimates and measures of association will be calculated using random effects models, and heterogeneity will be assessed at each stage of data synthesis. DISCUSSION: Through this review, we hope to quantify the proportion of PWUD at each progressive step and to help identify key individual, social, and structural points of leakage in the HCV care continuum for PWUD. In meeting these objectives, we will identify predictors to progress along the HCV care continuum, which can be used to inform policy to directly improve HCV care for PWUD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016034113. PMID- 27401501 TI - Subchondral linear hyperintensity of the femoral head: MR imaging findings and associations with femoro-acetabular joint pathology. AB - PURPOSE: The goal of this study was to evaluate the associations between linear hyperintensity in the subchondral bone of the femoral head on T2-weighted MR imaging and structural bone lesions. MATERIAL AND METHODS: The MR imaging examinations of 63 patients (66 hips) that showed a bone marrow edema pattern (BMEP) of the hip were retrospectively evaluated (study group). The study group comprised 43 men and 20 women, with a mean age of 55.3 years+/-16.9 (SD) (range: 19-84 years). A control group of 61 patients (77 hips) without BMEP of the hip on MR imaging was created. The control group comprised 30 men and 31 women, with a mean age of 53.1 years+/-15.6 (SD) (range: 25-83 years). The presence of linear abnormalities of the subchondral bone on T2-weighted fat-saturated sequences (TR/TE=4220-4340/42-45ms) was evaluated and MR imaging findings were correlated with structural femoro-acetabular pathology (advanced chondropathy, osteonecrosis, subchondral insufficiency fractures and macroscopic fractures) and with pain duration. RESULTS: A linear hyperintensity in the subchondral bone on T2-weighted MR imaging was found in 43/66 hips with areas of BMEP (65.1%) and in 3/77 hips without BMEP (3.8%). Subchondral linear hyperintensity was seen in 15/16 (93.7%) hips with a subchondral insufficiency fracture. Among the 16 hips with an ARCO stage III osteonecrosis, 13 (76.9%) presented BMEP associated with a subchondral linear hyperintensity. BMEP was present in 6/8 hips with ARCO stage IV osteonecrosis; however, only two hips (25%) exhibited subchondral linear hyperintensities. Finally, 77.7% of patients with subchondral linear hyperintensities presented with acute or subacute hip pain (P<0.0001). CONCLUSION: Femoral head subchondral linear hyperintensity on T2-weighted MR imaging is common and is associated with acute subchondral bone damage. PMID- 27401502 TI - Herman score in prenatal screening for Down syndrome: Can a junior assess a senior? AB - PURPOSE: To compare Herman scores self-assessed prospectively during ultrasound first-trimester screening by a single senior radiologist with 15 years of experience, to those obtained retrospectively by an unexperienced junior radiologist. MATERIALS AND METHODS: Over a 18-month period, a single senior radiologist measured the nuchal translucency thickness along with calculation of Herman scores. An independent junior radiologist subsequently reviewed and scored the images. RESULTS: A total of 301 patients were included. The mean Herman score was 8.2+/-0.9 (SD) for the senior radiologist and 7.8+/-0.9 (SD) after review by the independent junior radiologist (P<0.001). The scores for caliper position and fetal head position decreased significantly after the independent review. The two criteria on which the two operators disagreed the least were visualization of the nuchal translucency and the distinction between neck and amnios. CONCLUSION: Herman score is lower after review by a junior radiologist, without any effect on patient's management and follow-up. PMID- 27401503 TI - Through-Solvent Tunneling in Donor-Bridge-Acceptor Molecules Containing a Molecular Cleft. AB - Photoinduced electron transfer is used to investigate the solvent-mediated electron tunneling between electron donor and acceptor groups in polar solvents. Bis-peptide scaffolds are used to control the spatial positioning of electron donor and acceptor groups and create a molecular cleft. The photoinduced electron transfer is studied for two different cleft sizes, and the electronic coupling is found to be controlled by the nature of the solvent and the ability of the molecular cleft to accommodate it, as well as interact directly with it. These studies demonstrate the importance of electron tunneling through nonbonded contacts and reveal a strategy for examining such tunneling pathways in polar solvents. PMID- 27401504 TI - Arsenic distribution in waters and its geochemical behavior in sediment of Mahanadi estuary in India. AB - Distribution of arsenic in the marine environment is associated with its biogeochemical behavior. Indeed, very few studies have been conducted along the seasonal cycle to show its non-conservative behavior in the tropical estuary. The Mahanadi River, one of the major tropical rivers in the peninsular India, drains densely populated and industrialized region of Paradeep port. Over this 1-year study, the variations of inorganic arsenic were examined along the salinity gradient of the Mahanadi estuary, with the aim to provide some insights into the mechanisms that control arsenic concentrations and behavior under estuarine mixing. Arsenic in the estuary was derived from both natural and anthropogenic sources, and it displayed partial removal from the water in the mixing zone. Results of geo-accumulation index indicated that sediments were uncontaminated and they acted as a sink for arsenic. The diffusive fluxes from water to sediment were estimated to be 9.05 MUg m(-2) day(-1) at Chaumohona, 9.83 MUg m(-2) day(-1) at Kaudia, and 11.85 MUg m(-2) day(-1) at Neherubunglow. The findings of the study suggest that both the removal of arsenic by biogeochemical processes and its diffusive transport from water to sediment are of major importance for both the non-conservative behavior of arsenic in the estuary and its export to the coastal water. PMID- 27401506 TI - Measuring Burnout in Palliative Care: Authors' Reply. PMID- 27401505 TI - An Intervention to Enhance Goals-of-Care Communication Between Heart Failure Patients and Heart Failure Providers. AB - CONTEXT: Heart failure patients contend with a markedly impaired quality of life, experiencing emotional distress and severe physical discomfort that increases in frequency in the last months of life. Improving communication between patients and providers about goals of care has the potential to improve patient-provider communication and patient outcomes. OBJECTIVES: To determine the effects of a goals-of-care (GoC) intervention compared to usual care on the number of GoC conversations, quality of communication between patients and providers, referrals to palliative care services and completion of advance care directives. METHODS: A two-group randomized study (n = 40/group) compared a GoC intervention to usual care, conducted in an academic heart failure (HF) clinic. The GoC intervention was a previsit patient activation-education, telephone-based intervention delivered by a nurse. The primary outcome of the study was number of GoC conversations between HF patients and HF providers. Secondary outcomes were quality of communication, number of referrals to palliative care, and completion of advance directives. RESULTS: Patients averaged 58.15 +/- 11.26 years of age, with mean left ventricular ejection fraction = 30.31 +/- 9.72% and Seattle Heart Failure Model scores = 95.1 +/- 1.60. There was a significant increase in goals of-care conversations (58% vs. 2.6%, P < 0.001) and quality of end-of-life communication (P = 0.03) in the GoC group compared to usual care after the intervention. There were no differences between groups on the other outcomes. CONCLUSION: The GoC intervention resulted in more GoC conversations and higher quality communication between HF patients and providers without increased anxiety or depression. Further studies are needed to assess impact on longer term quality of care and patient outcomes. PMID- 27401507 TI - Shifting Focus in Pediatric Advance Care Planning: From Advance Directives to Family Engagement. PMID- 27401509 TI - Palliative Care Declarations: Mapping a New Form of Intervention. PMID- 27401508 TI - Impact of Prophylactic Fentanyl Pectin Nasal Spray on Exercise-Induced Episodic Dyspnea in Cancer Patients: A Double-Blind, Randomized Controlled Trial. AB - CONTEXT: Episodic breathlessness is common and debilitating in cancer patients. OBJECTIVES: In this pilot study, we examined the effect of prophylactic fentanyl pectin nasal spray (FPNS) on exercise-induced dyspnea, physiologic function, and adverse events. METHODS: In this parallel, double-blind randomized placebo controlled trial, opioid-tolerant patients performed three six-minute walk tests (6MWTs) to induce dyspnea. They were randomized to receive either FPNS (15%-25% of total daily opioid dose each time) or placebo 20 minutes before the second and third 6MWTs. We compared dyspnea Numeric Rating Scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the first and second 6MWTs (T2-T1) and between the first and third 6MWTs (T3-T1). RESULTS: Twenty-four patients enrolled, with 96% completion. FPNS was associated with significant within-arm reduction in dyspnea NRS at rest (T2-T1: 0.9 [95% CI -1.7, -0.1]; T3-T1: -1.3 [95% CI -2.0, -0.5]) and at the end of a 6MWT (T2-T1: -2.0 [95% CI -3.5, -0.6]; T3-T1: -2.3 [95% CI -4.0, -0.7]), and longer walk distance (T2-T1 +23.8 m [95% CI +1.3, +46.2 m]; T3-T1: +23.3 m [95% CI -1.7, +48.2]). In the placebo arm, we observed no significant change in walk distance nor dyspnea NRS at rest, but significant reduction in dyspnea NRS at six minutes (T2-T1: -1.7 [95% CI -3.3, -0.1]; T3-T1: -2.5 [95% CI -4.2, -0.9]). Vital signs, neurocognitive function, and adverse effects did not differ significantly. CONCLUSION: FPNS was safe, reduced dyspnea at rest, and increased walk distance in before-after comparison. The placebo effect was substantial, which needs to be factored in future study designs. TRIAL REGISTRATION: ClinicalTrials.govNCT01832402. PMID- 27401510 TI - Embedding Objective Measurements of Quality into Routine Practice in Hospice/Palliative Care. PMID- 27401511 TI - Resource Use and Health Care Costs of COPD Patients at the End of Life: A Systematic Review. AB - CONTEXT: Patients with chronic obstructive pulmonary disease (COPD) in their final months of life potentially place a high burden on health care systems. Concrete knowledge about resources used and costs incurred by those patients at the end of life is crucial for policymakers. OBJECTIVES: The aim of this systematic review was to describe the resources used and costs incurred by patients with COPD at the end of life. METHODS: We performed a comprehensive literature search in MEDLINE, Web of Science, and EconLit. We screened 886 abstracts and subsequently reviewed 80 full-text articles. Inclusion criteria were at least one type of resource use and/or cost outcome reported in adults diagnosed with COPD during an end-of-life period. Subsequently, we performed quality appraisal consistent with the ISPOR checklist for retrospective database studies and accomplished comprehensive data extraction. RESULTS: Ten articles fulfilled the inclusion criteria. Three, five, and two studies described European, North American, and Asian health care settings, respectively. All studies had a retrospective design and were published between 2006 and 2015. We observed a very variable resource use, an increased number of hospitalizations, intensive care unit stays, primary care consultations and medication prescriptions, as well as a lack of utilization of formal palliative care services in end-of-life COPD patients. Specific cost items were not well described. CONCLUSION: The high use of health care resources in COPD patients in the final months of life suggests a focus on prolonging life and a tendency toward aggressive care. Limiting potentially inappropriate care and improving the quality of end-of-life care in advanced COPD are, therefore, important public health challenges. PMID- 27401512 TI - Should the Treatment of Hypothyroidism Be Withdrawn in Hospice Care? PMID- 27401513 TI - Reasons for End-of-Life Hospital Admissions: Results of a Survey Among Family Physicians. AB - CONTEXT: Although the acute hospital setting is not considered to be an ideal place of death, many people are admitted to hospital at the end of life. OBJECTIVES: The present study aims to examine the reasons for hospital admissions that result in an expected death and the factors that play a role in the decision to admit to hospital. METHODS: This was a survey among family physicians (FPs) about those of their patients who had died nonsuddenly in an acute university hospital setting in Belgium between January and August 2014. Questions were asked about the patient's health situation, care that the patient received before the admission, the circumstances of the hospital admission, the reasons necessitating the admission, and other factors that had played a role in the decision to admit the patient to hospital. RESULTS: We received 245 completed questionnaires (response rate 70%), and 77% of those hospital deaths were considered to be nonsudden. FPs indicated that 55% of end-of-life hospitalizations were for palliative reasons and 26% curative or life-prolonging. Factors such as the patient feeling safer in hospital (35%) or family believing care to be better in hospital (54%) frequently played a role in the end-of-life hospitalization. When patients were admitted with a limited anticipated life expectancy, FPs were more likely to indicate that an inadequate caring capacity of the care setting had played a role in the admission. CONCLUSION: To reduce the number of hospital deaths, a combination of structural support for out-of-hospital end-of-life care and a more timely referral to out-of-hospital palliative care services may be needed. PMID- 27401514 TI - Randomized Pilot Trial of a Telephone Symptom Management Intervention for Symptomatic Lung Cancer Patients and Their Family Caregivers. AB - CONTEXT: Lung cancer is one of the most common cancers affecting both men and women and is associated with high symptom burden and psychological distress. Lung cancer patients' family caregivers also show high rates of distress. However, few interventions have been tested to alleviate significant problems of this population. OBJECTIVES: This study examined the preliminary efficacy of telephone based symptom management (TSM) for symptomatic lung cancer patients and their family caregivers. METHODS: Symptomatic lung cancer patients and caregivers (n = 106 dyads) were randomly assigned to four sessions of TSM consisting of cognitive behavioral and emotion-focused therapy or an education/support condition. Patients completed measures of physical and psychological symptoms, self-efficacy for managing symptoms, and perceived social constraints from the caregiver; caregivers completed measures of psychological symptoms, self-efficacy for helping the patient manage symptoms and managing their own emotions, perceived social constraints from the patient, and caregiving burden. RESULTS: No significant group differences were found for all patient outcomes and caregiver self-efficacy for helping the patient manage symptoms and caregiving burden at two- and six-weeks post-intervention. Small effects in favor of TSM were found regarding caregiver self-efficacy for managing their own emotions and perceived social constraints from the patient. Study outcomes did not significantly change over time in either group. CONCLUSION: Findings suggest that our brief telephone based psychosocial intervention is not efficacious for symptomatic lung cancer patients and their family caregivers. Next steps include examining specific intervention components in relation to study outcomes, mechanisms of change, and differing intervention doses and modalities. PMID- 27401515 TI - Palliative Care Specialist Consultation Is Associated With Supportive Care Quality in Advanced Cancer. AB - CONTEXT: Although recent randomized controlled trials support early palliative care for patients with advanced cancer, the specific processes of care associated with these findings and whether these improvements can be replicated in the broader health care system are uncertain. OBJECTIVES: The aim of this study was to evaluate the occurrence of palliative care consultation and its association with specific processes of supportive care in a national cohort of Veterans using the Cancer Quality ASSIST (Assessing Symptoms Side Effects and Indicators of Supportive Treatment) measures. METHODS: We abstracted data from 719 patients' medical records diagnosed with advanced lung, colorectal, or pancreatic cancer in 2008 over a period of three years or until death who received care in the Veterans Affairs Health System to evaluate the association of palliative care specialty consultation with the quality of supportive care overall and by domain using a multivariate regression model. RESULTS: All but 54 of 719 patients died within three years and 293 received at least one palliative care consult. Patients evaluated by a palliative care specialist at diagnosis scored seven percentage points higher overall (P < 0.001) and 11 percentage points higher (P < 0.001) within the information and care planning domain compared with those without a consult. CONCLUSION: Early palliative care specialist consultation is associated with better quality of supportive care in three advanced cancers, predominantly driven by improvements in information and care planning. This study supports the effectiveness of early palliative care consultation in three common advanced cancers within the Veterans Affairs Health System and provides a greater understanding of what care processes palliative care teams influence. PMID- 27401516 TI - Pain and Functional Status in Patients With Ventricular Assist Devices. AB - CONTEXT: Ventricular assist devices (VADs) have been shown to improve survival and overall quality of life, but there are limited data on pain control and functional status in this patient population. OBJECTIVES: This study examined changes in pain, functional status, and quality of life over time in VAD patients. METHODS: Patients were enrolled in this prospective cohort study before or as early after VAD implant as possible and then followed for up to 48 weeks. The Brief Pain Inventory was used to assess pain. The Katz Independent Activities of Daily Living questionnaire was used to assess functional status. The Kansas City Cardiomyopathy Questionnaire, a 23-item questionnaire covering five domains (physical function, symptoms, social function, self-efficacy, and quality of life), was used to assess quality of life and health status. RESULTS: Eighty seven patients were enrolled at four medical centers. The median Brief Pain Inventory severity score was 2.8 (interquartile range 0.5-5.0) before implantation and 0.0 (interquartile range 0.0-5.3) 48 weeks after implantation (P = 0.0009). Katz Independent Activities of Daily Living summary scores also demonstrated significant improvement over time (P < 0.0001). Kansas City Cardiomyopathy Questionnaire summary scales demonstrated significant improvement with time (P < 0.0016). CONCLUSION: This study demonstrated that patients with VADs experienced improved pain, functional status, and quality of life over time. These data may be useful to help patients make decisions when they are considering undergoing VAD implantation. PMID- 27401517 TI - Emerging Collaboration Between Palliative Care Specialists and Mechanical Circulatory Support Teams: A Qualitative Study. AB - CONTEXT: Despite national requirements mandating collaboration between palliative care specialists and mechanical circulatory support (MCS) teams at institutions that place destination therapy ventricular assist devices, little is known about the nature of those collaborations or outcomes for patients and families. OBJECTIVES: To assess how Centers for Medicare & Medicaid Services' regulations have changed collaboration between palliative care and MCS teams and how this collaboration is perceived by MCS team members. METHODS: After obtaining verbal consent, members of MCS teams were interviewed using semistructured telephone interviews. Interviews were transcribed, and content was coded and analyzed using qualitative methods. RESULTS: Models for collaboration varied widely between institutions. Several expected themes emerged from interviews: 1) improvements over time in the relationship between palliative care specialists and MCS teams, 2) palliative care specialists as facilitators of advance care planning, and 3) referral to hospice and ventricular assist device deactivation as specific areas for collaboration. Several unexpected themes also emerged: 4) the emergence of dedicated heart failure palliative care teams, 5) palliative care specialists as impartial voices in decision making, 6) palliative care specialists as extra support for MCS team members, and 7) the perception of improved patient and family experiences with palliative care team exposure. CONCLUSION: Although the structure of collaboration varies between institutions, collaboration between MCS teams and palliative care specialists is increasing and often preceded the Centers for Medicare & Medicaid Services requirement. Overall impressions of palliative care specialists are highly positive, with perceptions of improved patient and family experience and decreased burden on MCS team members. PMID- 27401518 TI - Incorrect Use of the English Language Term "Episodic". PMID- 27401519 TI - The Impact of Plasma Cholinergic Enzyme Activity and Other Risk Factors for the Development of Delirium in Patients Receiving Palliative Care. AB - CONTEXT: Delirium is an important complication in palliative care patients. One of the potential risk factors for cognitive disorders is deterioration in cholinergic neurotransmission. Anticholinergic medications are known to be important owing to the association of their metabolites with significant morbidity, which is often the result of cumulative effects of medications (anticholinergic burden). Additionally, cholinergic enzymes are possible candidates reflecting the cholinergic situation in patients. However, the role of cholinesterases (CHE) for delirium in palliative care patients is unknown. OBJECTIVES: Following local Ethics Board approval and written informed consent, we recruited a cohort of patients who had been admitted to the Heidelberg University Palliative Care Unit related to CHE and other factors at risk for delirium. METHODS: Delirium was assessed using the Nursing Delirium Screening Scale once daily in all cancer patients (N = 100) during their stay on the palliative care unit. In a subgroup of 69 probes, blood samples were analyzed for acetyl- and butyrylcholinesterase activity spectrophotometrically. Furthermore, patients' medications were recorded. Logistic regression analysis was used to evaluate potential predictors of delirium. RESULTS: Delirium was identified in 29% of patients. Karnofsky Performance Status Scale score was significantly lower (P = 0.021) and mortality higher (P = 0.018) in patients with delirium. Plasma CHE activity was not associated with delirium. However, a significant effect of anticholinergic medication on plasma CHE activity was detected; so far midazolam (P = 0.01) seems to play an important role in that process. CONCLUSION: Special care might be necessary with anticholinergic medication to minimize risk for delirium in palliative cancer patients. PMID- 27401520 TI - Pittsburgh compound B imaging and cerebrospinal fluid amyloid-beta in a multicentre European memory clinic study. AB - The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-beta42; (ii) centrally measured cerebrospinal fluid amyloid-beta42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-beta42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-beta production, by using the ratio of amyloid-beta42 to amyloid-beta40 Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer's and Parkinson's Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-beta42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-beta42 and amyloid-beta40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference measurement procedure findings was further improved when using amyloid-beta42/40 Agreement between Pittsburgh compound B visual ratings and Centiloids was near complete. Despite improved agreement between Pittsburgh compound B and centrally analysed cerebrospinal fluid, a minority of subjects showed discordant findings. While future studies are needed, our results suggest that amyloid biomarker results may not be interchangeable in some individuals. PMID- 27401521 TI - Defining secondary progressive multiple sclerosis. AB - A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step >=4 and pyramidal score >=2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32 33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis. PMID- 27401522 TI - Prenatal famine exposure has sex-specific effects on brain size. AB - Early nutritional deprivation might cause irreversible damage to the brain. Prenatal exposure to undernutrition has been shown to be associated with increased central nervous system anomalies at birth and decreased cognitive function in adulthood. Little is known about the potential effect on the brain in older age. We investigated brain size and structure at age 68 years after prenatal famine exposure. T1-weighted structural magnetic resonance images of the brain were made in 118 Dutch famine birth cohort members. Of these 118 (44% male, age range 65-69 years), 41 had been exposed to famine in early gestation and 77 had been prenatally unexposed. Structural volumes were automatically assessed using FreeSurfer. Diffusion tensor imaging was performed and anisotropy and diffusivity were computed. Fluid attenuated inversion recovery was performed to assess white matter hyperintensities. Exposure to famine in early gestation was associated with smaller intracranial volume in males, but not females. Volumes of total brain, grey and white matter were also smaller in early exposed males, but these differences disappeared after adjusting for intracranial volume. Prenatally exposed males but not females, had a smaller intracranial and total brain volume compared to unexposed subjects. Our findings show that prenatal undernutrition permanently affected brain size.media 1vid110.1093/brain/aww132_video_abstractaww132_video_abstract. PMID- 27401523 TI - Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease. AB - BACKGROUND AND OBJECTIVES: An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties. RESULTS: Seventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival. CONCLUSIONS: To our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country wide studies to improve our understanding of the etiology of anti-GBM disease. PMID- 27401524 TI - New Insights into Dialysis Vascular Access: What Is the Optimal Vascular Access Type and Timing of Access Creation in CKD and Dialysis Patients? AB - Optimal vascular access planning begins when the patient is in the predialysis stages of CKD. The choice of optimal vascular access for an individual patient and determining timing of access creation are dependent on a multitude of factors that can vary widely with each patient, including demographics, comorbidities, anatomy, and personal preferences. It is important to consider every patient's ESRD life plan (hence, their overall dialysis access life plan for every vascular access creation or placement). Optimal access type and timing of access creation are also influenced by factors external to the patient, such as surgeon experience and processes of care. In this review, we will discuss the key determinants in optimal access type and timing of access creation for upper extremity arteriovenous fistulas and grafts. PMID- 27401525 TI - New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes. AB - Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it. PMID- 27401526 TI - Clustering of Anti-GBM Disease: Clues to an Environmental Trigger? PMID- 27401527 TI - New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes. AB - Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes. PMID- 27401528 TI - Cause and occurrence timing of osteoradionecrosis of the jaw: a retrospective study focusing on prophylactic tooth extraction. AB - PURPOSE: This retrospective study aimed to analyze the relationship between tooth extraction and osteoradionecrosis (ORN) occurrence. The irradiation field, dose, and time interval between radiotherapy (RT) and ORN were reviewed. We also discuss appropriate guidelines for prophylactic tooth extraction. METHODS: A total of 33 patients treated for grade >=2 (clinical) ORN in our department from 2002 to 2014 were enrolled. The following epidemiological data were retrospectively gathered: age, sex, histological diagnosis, primary tumor sites, radiation dose, chemotherapy, site of ORN, relationship between tooth extraction and ORN occurrence, and time interval between tooth extraction and the initiation or end of RT. RESULTS: Twenty-one percent of ORN cases resulted from tooth extraction. The most common site of ORN (82 %) was the mandibular molar region. About half of ORN cases (49 %) occurred within 2 years after RT. All patients who received tooth extraction after RT developed ORN (100 %) independently of time interval between tooth extraction and the end of RT (median interval, 37.5 months; range, 27-120 months). In contrast, only 50 % of patients who received tooth extraction before RT developed ORN. There may have been an association between the irradiation field and the site of ORN development CONCLUSIONS: ORN occurrence due to tooth extraction was 21 %. Occurrence timing of ORN did not depend on time interval between tooth extraction and the end of RT. The irradiation field is certainly related to the site of ORN; therefore, prophylactic tooth extraction should be performed in consideration of the proposed radiation field and dose. PMID- 27401529 TI - Negative symptoms: History of the concept and their position in diagnosis of schizophrenia. AB - Current conceptualizations of schizophrenia have been introduced over centuries and continue to progress in recent decades. Symptoms have been divided into several domains, contrasting negative and positive symptoms which are different in their nature, onset, progression and response to treatment. An account of the different historical changes of the concept - essentially nosographic - has led to models attempting to integrate findings for each dimension of the disorder. This paper reviews the history of negative symptoms in diagnosis and how different approaches have been utilised to consider negative symptoms in the concept of schizophrenia. The paper also bridges various international classifications which have evolved and modified the role of negative symptoms in their diagnostic criteria for schizophrenia, which highlights the challenge of defining this disease. PMID- 27401530 TI - Sexual dimorphism of the cerebellar vermis in schizophrenia. AB - Converging lines of evidence implicate structural and functional abnormalities in the cerebellum in schizophrenia (SCZ). The cerebellar vermis is of particular interest given its association with clinical symptoms and cognitive deficits in SCZ and its known connections with cortical regions such as the prefrontal cortex. Prior neuroimaging studies have shown structural and functional abnormalities in the vermis in SCZ. In this study, we examined the cerebellar vermis in 50 individuals with SCZ and 54 healthy controls (HC) using a quantitative volumetric approach. All participants underwent high-resolution structural magnetic resonance imaging (MRI). The vermis was manually traced for each participant, and vermis volumes were computed using semiautomated methods. Volumes for total vermis and vermis subregions (anterior and posterior vermis) were analyzed in the SCZ and HC groups. Significant diagnosis-by-sex interaction effects were found in total vermis and vermis subregion analyses. These effects appeared to be driven by significantly decreased posterior vermis volumes in males with SCZ. Exploratory analyses did not reveal significant effects of clinical variables (FEP status, illness duration, and BPRS total score and subscores) on vermis volumes. The findings herein highlight the presence of neural sex differences in SCZ and the need for considering sex-related factors in studying the disorder. PMID- 27401531 TI - Two-stage replication of previous genome-wide association studies of AS3MT-CNNM2 NT5C2 gene cluster region in a large schizophrenia case-control sample from Han Chinese population. AB - Schizophrenia is a devastating psychiatric condition with high heritability. Replicating the specific genetic variants that increase susceptibility to schizophrenia in different populations is critical to better understand schizophrenia. CNNM2 and NT5C2 are genes recently identified as susceptibility genes for schizophrenia in Europeans, but the exact mechanism by which these genes confer risk for schizophrenia remains unknown. In this study, we examined the potential for genetic susceptibility to schizophrenia of a three-gene cluster region, AS3MT-CNNM2-NT5C2. We implemented a two-stage strategy to conduct association analyses of the targeted regions with schizophrenia. A total of 8218 individuals were recruited, and 45 pre-selected single nucleotide polymorphisms (SNPs) were genotyped. Both single-marker and haplotype-based analyses were conducted in addition to imputation analysis to increase the coverage of our genetic markers. Two SNPs, rs11191419 (OR=1.24, P=7.28*10(-5)) and rs11191514 (OR=1.24, P=0.0003), with significant independent effects were identified. These results were supported by the data from both the discovery and validation stages. Further haplotype and imputation analyses also validated these results, and bioinformatics analyses indicated that CALHM1, which is located approximately 630kb away from CNNM2, might be a susceptible gene for schizophrenia. Our results provide further support that AS3MT, CNNM2 and CALHM1 are involved with the etiology and pathogenesis of schizophrenia, suggesting these genes are potential targets of interest for the improvement of disease management and the development of novel pharmacological strategies. PMID- 27401532 TI - Transgenerational effects of genocide exposure on the risk and course of schizophrenia: A population-based study. AB - BACKGROUND: Hypotheses about the sequel of parental genocide exposures on the offspring's risk and course of schizophrenia remain untested. AIMS: To test hypotheses related to the transgenerational transmission of parental genocide exposure on the risk and course of schizophrenia. METHODS: Data were extracted from the National Population Register on all offspring (N=51.233; born: 1948 1989) whose parents were born (1922 to 1945) in Nazi- dominated European nations. Both parents either immigrated before (indirect exposure: n=1627, 3.2%) or after (direct exposure: n=49.606, 96.8%) the Nazi era. Offspring subgroups were identified from the initial timing of parental exposure (e.g., likely in utero, combined in utero and postnatal, or postnatal). Schizophrenia disorders were ascertained (1950-2014) from the National Psychiatric Case Registry. Cox models were computed to compare the offspring groups with respect to the risk and the adverse course of schizophrenia, adjusting for confounders. RESULTS: The offspring rates on the risk and course of schizophrenia did not differ by parental affiliation to the direct and indirect exposure groups. Cox models showed that offspring subgroups with maternal Holocaust exposures in utero only (HR=1.74, 1.13, 2.66) and combined in utero and postnatal (HR=1.48, 1.05, 2.10); as well as paternal Holocaust exposures combined in utero and postnatal (HR=1.48, 1.08, 2.05), and early postnatal (aged 1-2; HR=1.49, 1.10, 2.00) had a significantly (P<0.05) higher psychiatric re-hospitalization rate than the indirect group. CONCLUSIONS: Transgenerational genocide exposure was unrelated to the risk of schizophrenia in the offspring, but was related to a course of deterioration during selected critical periods of early life. PMID- 27401533 TI - Evidence for a global oculomotor program in reading. AB - Recent corpus studies of eye-movements in reading revealed a substantial increase in saccade amplitudes and fixation durations as the eyes move over the first words of a sentence. This start-up effect suggests a global oculomotor program, which operates on the level of an entire line, in addition to the well established local programs operating within the visual span. The present study investigates the nature of this global program experimentally and examines whether the start-up effect is predicated on generic visual or specific linguistic characteristics and whether it is mainly reflected in saccade amplitudes, fixation durations or both measures. Eye movements were recorded while 38 participants read (a) normal sentences, (b) sequences of randomly shuffled words and (c) sequences of z-strings. The stimuli were, therefore, similar in their visual features, but varied in the amount of syntactic and lexical information. Further, the stimuli were composed of words or strings that either varied naturally in length (Nonequal condition) or were all restricted to a specific length within a sentence (Equal). The latter condition constrained the variability of saccades and served to dissociate effects of word position in line on saccade amplitudes and fixation durations. A robust start-up effect emerged in saccade amplitudes in all Nonequal stimuli, and-in an attenuated form-in Equal sentences. A start-up effect in single fixation durations was observed in Nonequal and Equal normal sentences, but not in z-strings. These findings support the notion of a global oculomotor program in reading particularly for the spatial characteristics of motor planning, which rely on visual rather than linguistic information. PMID- 27401535 TI - Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness. AB - Central blood pressure (BP) can be assessed noninvasively based on radial tonometry and may potentially be a better predictor of clinical outcome than brachial BP. However, the validity of noninvasively obtained estimates has never been examined in patients with chronic kidney disease (CKD). Here we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m(2)) and 41 controls without renal disease undergoing scheduled coronary angiography. BP in the ascending aorta was measured through the angiography catheter and simultaneously estimated using radial tonometry. The mean difference between estimated central and aortic SBP was -13.2 (95% confidence interval -14.9 to 11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml/min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected invasive SBP than estimated SBP. Thus, tonometry-based estimates of central BP progressively underestimate invasive central SBP with decreasing renal function and increasing arterial stiffness in CKD patients. PMID- 27401534 TI - Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract. AB - Diabetes mellitus is a systemic disease associated with a deficiency of insulin production or action. Diabetic patients have an increased susceptibility to infection with the urinary tract being the most common site. Recent studies suggest that Ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that plays an important role in protecting the urinary tract from bacterial insult. Because the impact of diabetes on RNase 7 expression and function are unknown, we investigated the effects of insulin on RNase 7 using human urine specimens. The urinary RNase 7 concentrations were measured in healthy control patients and insulin-deficient type 1 diabetics before and after starting insulin therapy. Compared with controls, diabetic patients had suppressed urinary RNase 7 concentrations, which increased with insulin. Using primary human urothelial cells, the mechanisms by which insulin stimulates RNase 7 synthesis were next explored. Insulin induced RNase 7 production via the phosphatidylinositide 3 kinase signaling pathway (PI3K/AKT) to shield urothelial cells from uropathogenic E. coli. In contrast, uropathogenic E. coli suppressed PI3K/AKT activity and RNase 7 production. Thus, insulin and PI3K/AKT signaling are essential for RNase 7 expression and increased infection risks in diabetic patients may be secondary to suppressed RNase 7 production. Our data may provide unique insight into novel urinary tract infection therapeutic strategies in at-risk populations. PMID- 27401536 TI - Retrospective and comparative analysis of (99m)Tc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women. AB - BACKGROUND: Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. METHODS: During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. RESULTS: A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). CONCLUSIONS: BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer. PMID- 27401537 TI - Exploring Patterns of Awareness and Use of HIV Pre-Exposure Prophylaxis Among Young Men Who Have Sex with Men. AB - Pre-exposure prophylaxis (PrEP) has shown promise as a safe and effective HIV prevention strategy, but there is limited research on awareness and use among young men who have sex with men (YMSM). Using baseline data from the "Keep It Up! 2.0" randomized control trial, we examined differences in PrEP awareness and use among racially diverse YMSM (N = 759; mean age = 24.2 years). Participants were recruited from study sites in Atlanta, Chicago, and New York City, as well as through national advertising on social media applications. While 67.5 % of participants reported awareness of PrEP, 8.7 % indicated using the medication. Awareness, but not use, varied by demographic variables. PrEP-users had twice as many condomless anal sex partners (ERR = 2.05) and more condomless anal sex acts (ERR = 1.60) than non-users. Future research should aim to improve PrEP awareness and uptake among YMSM and address condom use. PMID- 27401538 TI - What Factors Predict Who Will Have a Strong Social Network Following a Stroke? AB - PURPOSE: Measures of social networks assess the number and nature of a person's social contacts, and strongly predict health outcomes. We explored how social networks change following a stroke and analyzed concurrent and baseline predictors of social networks 6 months poststroke. METHOD: We conducted a prospective longitudinal observational study. Participants were assessed 2 weeks (baseline), 3 months, and 6 months poststroke. Measures comprised the Stroke Social Network Scale (Northcott & Hilari, 2013), Medical Outcomes Study Social Support Survey (Sherbourne & Stewart, 1991), National Institutes of Health Stroke Scale (Brott et al., 1989), Frenchay Aphasia Screening Test (Enderby, Wood, Wade, & Langton Hewer, 1987), Frenchay Activities Index (Wade, Legh-Smith, & Langton Hewer, 1985), and Barthel Index (Mahoney, Wood, & Barthel, 1958). Analyses of variance and standard multiple regression were used to analyze change and identify predictors. RESULTS: Eighty-seven participants (37% with aphasia) were recruited; 71 (16% with aphasia) were followed up at 6 months. Social network scores declined poststroke (p = .001). Whereas the Children and Relatives factors remained stable, the Friends factor significantly weakened (p < .001). Concurrent predictors of social network at 6 months were perceived social support, ethnicity, aphasia, and extended activities of daily living (adjusted R2 = .42). There were 2 baseline predictors: premorbid social network and aphasia (adjusted R2 = .60). CONCLUSIONS: Social networks declined poststroke. Aphasia was the only stroke-related factor measured at the time of the stroke that predicted social network 6 months later. PMID- 27401539 TI - Diversity and constraints in the floral morphological evolution of Leandra s.str. (Melastomataceae). AB - BACKGROUND AND AIMS: Putative processes related to floral diversification and its relation to speciation are still largely unaccounted for in the Melastomataceae. Leandra s.str. is one of the most diverse lineages of the Neotropical Miconieae and ranks among the ten most diverse groups in the Atlantic Forest. Here, we describe the floral diversity of this lineage in a continuous framework and address several questions related to floral evolution and putative developmental and environmental constraints in its morphology. METHODS: The morphological data set includes individual size measurements and shape scores (from elliptical Fourier analysis) for hypanthia, petals, stamens and styles. We evaluate whether there is evidence of correlation among these floral structures, shifts and convergent patterns, and association of these traits with elevation. KEY RESULTS: Leandra s.str. flower structures present a strong phylogenetic signal and tend to be conserved among close relatives. The extremes in flower regimes seem to be quite distinct, but non-overlapping discrete flower types are not observed. Overall, the morphology of Leandra s.str. floral structures is correlated, and anther colour and inflorescence architecture correlate with flower structures. Additionally, the rates of species diversification and morphological evolution are correlated in most clades. CONCLUSIONS: Although some flower regimes tend to occur in different elevational ranges, no significant association is observed. The general idea that hypanthium-ovary fusion is associated with fruit types in the Melastomataceae does not hold for Leandra s.str., where, instead, hypanthium ovary fusion seems to be associated with anther shape. The lowest rate of flower morphological change, when compared with species diversification rates, is observed in the clade that possesses the most specialized flowers in the group. While stuck on a single general pollination system, Leandra s.str. seems to be greatly wandering around it, given the flower diversity and convergent patterns observed in this group. PMID- 27401541 TI - Bottom-up synthesis of chiral covalent organic frameworks and their bound capillaries for chiral separation. AB - Covalent organic frameworks (COFs) are a novel class of porous materials, and offer great potential for various applications. However, the applications of COFs in chiral separation and chiral catalysis are largely underexplored due to the very limited chiral COFs available and their challenging synthesis. Here we show a bottom-up strategy to construct chiral COFs and an in situ growth approach to fabricate chiral COF-bound capillary columns for chiral gas chromatography. We incorporate the chiral centres into one of the organic ligands for the synthesis of the chiral COFs. We subsequently in situ prepare the COF-bound capillary columns. The prepared chiral COFs and their bound capillary columns give high resolution for the separation of enantiomers with excellent repeatability and reproducibility. The proposed strategy provides a promising platform for the synthesis of chiral COFs and their chiral separation application. PMID- 27401540 TI - On the persistence of reproductive barriers in Eucalyptus: the bridging of mechanical barriers to zygote formation by F1 hybrids is counteracted by intrinsic post-zygotic incompatibilities. AB - BACKGROUND AND AIMS: Many previous studies conclude that pre-zygotic barriers such as mechanical isolation account for most reproductive isolation between pairs of taxa. However, the inheritance and persistence of barriers such as these after the first generation of hybridization is rarely quantified, even though it is a vital consideration in understanding gene flow potential. There is an asymmetrical pre-zygotic mechanical barrier to hybridization between Eucalyptus nitens and Eucalyptus globulus, which completely prevents small-flowered E. nitens pollen from mating with large E. globulus flowers, while the reverse cross is possible. We aimed to determine the relative importance of pre- and post zygotic barriers in preventing gene flow following secondary contact between E. nitens and E. globulus, including the inheritance of barriers in advanced generation hybrids. METHODS: Experimental crossing was used to produce outcrossed E. nitens, E. globulus and their F1, F2, BCg and BCn hybrids. The strength and inheritance of a suite of pre- and post-zygotic barriers were assessed, including 20-year survival, growth and reproductive capacity. KEY RESULTS: The mechanical barrier to hybridization was lost or greatly reduced in the F1 hybrid. In contrast, intrinsic post-zygotic barriers were strong and persistent. Line-cross analysis indicated that the outbreeding depression in the hybrids was best explained by epistatic loss. CONCLUSIONS: The removal of strong mechanical barriers between E. nitens and E. globulus allows F1 hybrids to act as a bridge for bi-directional gene flow between these species. However, strong and persistent post-zygotic barriers exist, meaning that wherever F1 hybridization does occur, intrinsic post-zygotic barriers will be responsible for most reproductive isolation in this system. This potential transient nature of mechanical barriers to zygote formation due to additive inheritance in hybrids appears under-appreciated, and highlights the often important role that intrinsic post-mating barriers play in maintaining species boundaries at zones of secondary contact. PMID- 27401542 TI - The use of intrathecal fluorescein in cerebrospinal fluid leak repair: management from an anesthesiologist's point-of-view. PMID- 27401543 TI - Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice. AB - BACKGROUND: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation. METHODS: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice. RESULTS: TPA led to localized skin inflammation with increased epidermal thickness, infiltration of inflammatory-like cells and augmented tissue interleukin-17F levels. Systemic effects of the topical application of TPA were demonstrated by increased plasma concentration of serum amyloid A and splenic immune modulation, respectively. However, atherosclerotic plaque area and composition, and mRNA levels of several inflammatory genes in the aortic wall were not significantly affected by TPA-induced skin inflammation. CONCLUSIONS: TPA-induced psoriasis-like skin inflammation in atherosclerosis prone ApoE(-/-) mice evoked systemic immune-inflammatory effects, but did not affect atherogenesis. The results may question the role of psoriasis-induced inflammation in the pathogenesis of atherosclerosis in psoriasis patients. PMID- 27401544 TI - Efficacy of eculizumab against Eosinophilic Fasciitis associated with Paroxysmal Nocturnal Haemoglobinuria. PMID- 27401545 TI - Structural Analysis of an Avr4 Effector Ortholog Offers Insight into Chitin Binding and Recognition by the Cf-4 Receptor. AB - Chitin is a key component of fungal cell walls and a potent inducer of innate immune responses. Consequently, fungi may secrete chitin-binding lectins, such as the Cf-Avr4 effector protein from the tomato pathogen Cladosporium fulvum, to shield chitin from host-derived chitinases during infection. Homologs of Cf-Avr4 are found throughout Dothideomycetes, and despite their modest primary sequence identity, many are perceived by the cognate tomato immune receptor Cf-4. Here, we determined the x-ray crystal structure of Pf-Avr4 from the tomato pathogen Pseudocercospora fuligena, thus providing a three-dimensional model of an Avr4 effector protein. In addition, we explored structural, biochemical, and functional aspects of Pf-Avr4 and Cf-Avr4 to further define the biology of core effector proteins and outline a conceptual framework for their pleiotropic recognition by single immune receptors. We show that Cf-Avr4 and Pf-Avr4 share functional specificity in binding (GlcNAc)6 and in providing protection against plant- and microbial-derived chitinases, suggesting a broader role beyond deregulation of host immunity. Furthermore, structure-guided site-directed mutagenesis indicated that residues in Pf-Avr4 important for binding chitin do not directly influence recognition by Cf-4 and further suggested that the property of recognition is structurally separated or does not fully overlap with the virulence function of the effector. PMID- 27401548 TI - Time to decompensated cirrhosis and hepatocellular carcinoma after an HBV or HCV notification: A population-based study. AB - BACKGROUND & AIMS: Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise "late hepatitis notification" among people with an HBV/HCV notification and advanced liver disease in New South Wales, Australia. METHODS: HBV/HCV notifications 1995-2012 were linked to cancer registry and hospital admissions. Late hepatitis notification was defined by a notification after, at the time, or within two years before DC/HCC diagnosis. RESULTS: HBV and HCV cohorts comprised 50,958 and 79,727 individuals, respectively. Among people with DC (n=3869), late HBV notification declined from 64% (88/138) during 2001 2002 to 31% (46/149) in 2011-2012 (p<0.001), and late HCV notification declined from 52% (179/341) during 2001-2002 to 22% (134/605) in 2011-2012 (p<0.001). Among people with HCC (n=1656), late HBV notification declined from 68% (59/87) during 2001-2002 to 29% (37/128) in 2011-2012 (p<0.001), and late HCV notification declined from 51% (40/79) during 2001-2002 to 17% (49/288) in 2011 2012 (p<0.001). CONCLUSIONS: Despite significant declines in late hepatitis notification since early 2000s, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. LAY SUMMARY: Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase the risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise "late hepatitis notification" among people with an HBV or HCV notification in New South Wales, Australia. Late hepatitis notifications have significantly declined since early 2000s; however, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population level HBV/HCV screening. PMID- 27401546 TI - IQGAP2 is a novel interferon-alpha antiviral effector gene acting non conventionally through the NF-kappaB pathway. AB - BACKGROUND & AIMS: Type I interferons (IFN) provide the first line of defense against invading pathogens but its mechanism of action is still not well understood. Using unbiased genome-wide siRNA screens, we recently identified IQ motif containing GTPase activating protein 2 (IQGAP2), a tumor suppressor predominantly expressed in the liver, as a novel gene putatively required for IFN antiviral response against hepatitis C virus (HCV) infection. Here we sought to characterize IQGAP2 role in IFN response. METHODS: We used transient small interfering RNA knockdown strategy in hepatic cell lines highly permissive to JFH1 strain of HCV infection. RESULTS: We found that IQGAP2 acts downstream of IFN binding to its receptor, and independently of the JAK-STAT pathway, by physically interacting with RelA (also known as p65), a subunit of the NF-kappaB transcription factor. Interestingly, our data reveal a mechanism distinct from the well-characterized role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) in IFN production. Indeed, IFN alone was sufficient to stimulate NF-kappaB-dependent transcription in the absence of viral infection. Finally, both IQGAP2 and RelA were required for the induction by IFN of a subset of IFN-stimulated genes (ISG) with known antiviral properties. CONCLUSIONS: Our data identify a novel function for IQGAP2 in IFN antiviral response in hepatoma cells. We demonstrate the involvement of IQGAP2 in regulating ISG induction by IFN in an NF-kappaB-dependent manner. The IQGAP2 pathway may provide new targets for antiviral strategies in the liver, and may have a wider therapeutic implication in other disease pathogeneses driven by NF-kappaB activation. LAY SUMMARY: In this study, we identify a novel mechanism of action of interferon involving the IQGAP2 protein and the NF-kappaB pathway that is ultimately protective against hepatitis C virus infection. This newly identified pathway functions independently of the well-known STAT pathway and may therefore provide new targets for antiviral strategies in the liver. PMID- 27401549 TI - Temperature-related mortality estimates after accounting for the cumulative effects of air pollution in an urban area. AB - BACKGROUND: To propose a new method for including the cumulative mid-term effects of air pollution in the traditional Poisson regression model and compare the temperature-related mortality risk estimates, before and after including air pollution data. RESULTS: The analysis comprised a total of 56,920 residents aged 65 years or older who died from circulatory and respiratory diseases in Belgrade, Serbia, and daily mean PM10, NO2, SO2 and soot concentrations obtained for the period 2009-2014. After accounting for the cumulative effects of air pollutants, the risk associated with cold temperatures was significantly lower and the overall temperature-attributable risk decreased from 8.80 to 3.00 %. Furthermore, the optimum range of temperature, within which no excess temperature-related mortality is expected to occur, was very broad, between -5 and 21 degrees C, which differs from the previous findings that most of the attributable deaths were associated with mild temperatures. CONCLUSIONS: These results suggest that, in polluted areas of developing countries, most of the mortality risk, previously attributed to cold temperatures, can be explained by the mid-term effects of air pollution. The results also showed that the estimated relative importance of PM10 was the smallest of four examined pollutant species, and thus, including PM10 data only is clearly not the most effective way to control for the effects of air pollution. PMID- 27401550 TI - Time to move the fat. AB - In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transition to adulthood in Caenorhabditis elegans This novel connection involves cross-tissue signaling from the hypodermis (epidermis) to the intestine to promote reproductive success in the germline. PMID- 27401551 TI - Regulating telomere length from the inside out: the replication fork model. AB - Telomere length is regulated around an equilibrium set point. Telomeres shorten during replication and are lengthened by telomerase. Disruption of the length equilibrium leads to disease; thus, it is important to understand the mechanisms that regulate length at the molecular level. The prevailing protein-counting model for regulating telomerase access to elongate the telomere does not explain accumulating evidence of a role of DNA replication in telomere length regulation. Here I present an alternative model: the replication fork model that can explain how passage of a replication fork and regulation of origin firing affect telomere length. PMID- 27401553 TI - Mitosis-associated repression in development. AB - Transcriptional repression is a pervasive feature of animal development. Here, we employ live-imaging methods to visualize the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm of early Drosophila embryos. Snail target enhancers were attached to an MS2 reporter gene, permitting detection of nascent transcripts in living embryos. The transgenes exhibit initially broad patterns of transcription but are refined by repression in the mesoderm following mitosis. These observations reveal a correlation between mitotic silencing and Snail repression. We propose that mitosis and other inherent discontinuities in transcription boost the activities of sequence specific repressors, such as Snail. PMID- 27401552 TI - RB1: a prototype tumor suppressor and an enigma. AB - The retinoblastoma susceptibility gene (RB1) was the first tumor suppressor gene to be molecularly defined. RB1 mutations occur in almost all familial and sporadic forms of retinoblastoma, and this gene is mutated at variable frequencies in a variety of other human cancers. Because of its early discovery, the recessive nature of RB1 mutations, and its frequency of inactivation, RB1 is often described as a prototype for the class of tumor suppressor genes. Its gene product (pRB) regulates transcription and is a negative regulator of cell proliferation. Although these general features are well established, a precise description of pRB's mechanism of action has remained elusive. Indeed, in many regards, pRB remains an enigma. This review summarizes some recent developments in pRB research and focuses on progress toward answers for the three fundamental questions that sit at the heart of the pRB literature: What does pRB do? How does the inactivation of RB change the cell? How can our knowledge of RB function be exploited to provide better treatment for cancer patients? PMID- 27401554 TI - The C2H2-ZF transcription factor Zfp335 recognizes two consensus motifs using separate zinc finger arrays. AB - The complexities of DNA recognition by transcription factors (TFs) with multiple Cys2-His2 zinc fingers (C2H2-ZFs) remain poorly studied. We previously reported a mutation (R1092W) in the C2H2-ZF TF Zfp335 that led to selective loss of binding at a subset of targets, although the basis for this effect was unclear. We show that Zfp335 binds DNA and drives transcription via recognition of two distinct consensus motifs by separate ZF clusters and identify the specific motif interaction disrupted by R1092W. Our work presents Zfp335 as a model for understanding how C2H2-ZF TFs may use multiple recognition motifs to control gene expression. PMID- 27401555 TI - A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM 1 signaling to modulate fat transport. AB - Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood. This developmental timing pathway, which is controlled by the lin-4 and let-7 miRNAs, engages mTOR signaling in the intestine. The intestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway to modulate the activity of the serum/glucocorticoid-regulated kinase (SGK-1). Surprisingly, SGK-1 functions independently of DAF-16/FoxO; instead, SGK-1 promotes the cytoplasmic localization of the PQM-1 transcription factor, which antagonizes intestinal fat mobilization at the transcriptional level when localized to the nucleus. These results revealed that a non-cell autonomous developmental input regulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of fat reserves from the soma to the germline. PMID- 27401556 TI - The epidermis coordinates auxin-induced stem growth in response to shade. AB - Growth of a complex multicellular organism requires coordinated changes in diverse cell types. These cellular changes generate organs of the correct size, shape, and functionality. In plants, the growth hormone auxin induces stem elongation in response to shade; however, which cell types of the stem perceive the auxin signal and contribute to organ growth is poorly understood. Here, we blocked the transcriptional response to auxin within specific tissues to show that auxin signaling is required in many cell types for correct hypocotyl growth in shade, with a key role for the epidermis. Combining genetic manipulations in Arabidopsis thaliana with transcriptional profiling of the hypocotyl epidermis from Brassica rapa, we show that auxin acts in the epidermis in part by inducing activity of the locally acting, growth-promoting brassinosteroid pathway. Our findings clarify cell-specific auxin function in the hypocotyl and highlight the complexity of cell type interactions within a growing organ. PMID- 27401557 TI - HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer. AB - Ovarian cancer cells disseminate readily within the peritoneal cavity, which promotes metastasis, and are often resistant to chemotherapy. Ovarian cancer patients tend to present with advanced disease, which also limits treatment options; consequently, new therapies are required. The oncoprotein tyrosine kinase MET, which is the receptor for hepatocyte growth factor (HGF), has been implicated in ovarian tumorigenesis and has been the subject of extensive drug development efforts. Here, we report a novel ligand- and autophosphorylation independent activation of MET through the nonreceptor tyrosine kinase feline sarcoma-related (FER). We demonstrated that the levels of FER were elevated in ovarian cancer cell lines relative to those in immortalized normal surface epithelial cells and that suppression of FER attenuated the motility and invasive properties of these cancer cells. Furthermore, loss of FER impaired the metastasis of ovarian cancer cells in vivo. Mechanistically, we demonstrated that FER phosphorylated a signaling site in MET: Tyr1349. This enhanced activation of RAC1/PAK1 and promoted a kinase-independent scaffolding function that led to recruitment and phosphorylation of GAB1 and the specific activation of the SHP2 ERK signaling pathway. Overall, this analysis provides new insights into signaling events that underlie metastasis in ovarian cancer cells, consistent with a prometastatic role of FER and highlighting its potential as a novel therapeutic target for metastatic ovarian cancer. PMID- 27401558 TI - The Nrd1-like protein Seb1 coordinates cotranscriptional 3' end processing and polyadenylation site selection. AB - Termination of RNA polymerase II (RNAPII) transcription is associated with RNA 3' end formation. For coding genes, termination is initiated by the cleavage/polyadenylation machinery. In contrast, a majority of noncoding transcription events in Saccharomyces cerevisiae does not rely on RNA cleavage for termination but instead terminates via a pathway that requires the Nrd1-Nab3 Sen1 (NNS) complex. Here we show that the Schizosaccharomyces pombe ortholog of Nrd1, Seb1, does not function in NNS-like termination but promotes polyadenylation site selection of coding and noncoding genes. We found that Seb1 associates with 3' end processing factors, is enriched at the 3' end of genes, and binds RNA motifs downstream from cleavage sites. Importantly, a deficiency in Seb1 resulted in widespread changes in 3' untranslated region (UTR) length as a consequence of increased alternative polyadenylation. Given that Seb1 levels affected the recruitment of conserved 3' end processing factors, our findings indicate that the conserved RNA-binding protein Seb1 cotranscriptionally controls alternative polyadenylation. PMID- 27401559 TI - Toward the mechanism of eIF4F-mediated ribosomal attachment to mammalian capped mRNAs. AB - Ribosomal attachment to mammalian capped mRNAs is achieved through the cap eukaryotic initiation factor 4E (eIF4E)-eIF4G-eIF3-40S chain of interactions, but the mechanism by which mRNA enters the mRNA-binding channel of the 40S subunit remains unknown. To investigate this process, we recapitulated initiation on capped mRNAs in vitro using a reconstituted translation system. Formation of initiation complexes at 5'-terminal AUGs was stimulated by the eIF4E-cap interaction and followed "the first AUG" rule, indicating that it did not occur by backward scanning. Initiation complexes formed even at the very 5' end of mRNA, implying that Met-tRNAi (Met) inspects mRNA from the first nucleotide and that initiation does not have a "blind spot." In assembled initiation complexes, the cap was no longer associated with eIF4E. Omission of eIF4A or disruption of eIF4E-eIF4G-eIF3 interactions converted eIF4E into a specific inhibitor of initiation on capped mRNAs. Taken together, these results are consistent with the model in which eIF4E-eIF4G-eIF3-40S interactions place eIF4E at the leading edge of the 40S subunit, and mRNA is threaded into the mRNA-binding channel such that Met-tRNAi (Met) can inspect it from the first nucleotide. Before entering, eIF4E likely dissociates from the cap to overcome steric hindrance. We also found that the m(7)G cap specifically interacts with eIF3l. PMID- 27401560 TI - Agrochemical-induced stress in stingless bees: peculiarities, underlying basis, and challenges. AB - The toxicological stress induced by pesticides, particularly neonicotinoid insecticides, and its consequences in bees has been the focus of much recent attention, particularly for honey bees. However, the emphasis on honey bees and neonicotinoids has led to neglect of the relevance of stingless bees, the prevailing pollinators of natural and agricultural tropical ecosystems, and of other agrochemicals, including other pesticides and even leaf fertilizers. Consequently, studies focusing on agrochemical effects on stingless bees are sparse, usually limited to histopathological studies, and lack a holistic assessment of the effects of these compounds on physiology and behavior. Such effects have consequences for individual and colony fitness and are likely to affect both the stingless bee populations and the associated community, thereby producing a hierarchy of consequences thus far overlooked. Herein, we review the current literature on stingless bee-agrochemical interactions and discuss the underlying mechanisms involved in reported stress symptoms, as well as the potential consequences based on the peculiarities of these pollinators. PMID- 27401561 TI - Interaction of Avibactam with Class B Metallo-beta-Lactamases. AB - beta-Lactamases are the most important mechanisms of resistance to the beta lactam antibacterials. There are two mechanistic classes of beta-lactamases: the serine beta-lactamases (SBLs) and the zinc-dependent metallo-beta-lactamases (MBLs). Avibactam, the first clinically useful non-beta-lactam beta-lactamase inhibitor, is a broad-spectrum SBL inhibitor, which is used in combination with a cephalosporin antibiotic (ceftazidime). There are multiple reports on the interaction of avibactam with SBLs but few such studies with MBLs. We report biochemical and biophysical studies on the binding and reactivity of avibactam with representatives from all 3 MBL subfamilies (B1, B2, and B3). Avibactam has only limited or no activity versus MBL-mediated resistance in pathogens. Avibactam does not inhibit MBLs and binds only weakly to most of the MBLs tested; in some cases, avibactam undergoes slow hydrolysis of one of its urea N-CO bonds followed by loss of CO2, in a process different from that observed with the SBLs studied. The results suggest that while the evolution of MBLs that more efficiently catalyze avibactam hydrolysis should be anticipated, pursuing the development of dual-action SBL and MBL inhibitors based on the diazabicyclooctane core of avibactam may be productive. PMID- 27401562 TI - Inhibition and Dispersal of Pseudomonas aeruginosa Biofilms by Combination Treatment with Escapin Intermediate Products and Hydrogen Peroxide. AB - Escapin is an l-amino acid oxidase that acts on lysine to produce hydrogen peroxide (H2O2), ammonia, and equilibrium mixtures of several organic acids collectively called escapin intermediate products (EIP). Previous work showed that the combination of synthetic EIP and H2O2 functions synergistically as an antimicrobial toward diverse planktonic bacteria. We initiated the present study to investigate how the combination of EIP and H2O2 affected bacterial biofilms, using Pseudomonas aeruginosa as a model. Specifically, we examined concentrations of EIP and H2O2 that inhibited biofilm formation or fostered disruption of established biofilms. High-throughput assays of biofilm formation using microtiter plates and crystal violet staining showed a significant effect from pairing EIP and H2O2, resulting in inhibition of biofilm formation relative to biofilm formation in untreated controls or with EIP or H2O2 alone. Similarly, flow cell analysis and confocal laser scanning microscopy revealed that the EIP and H2O2 combination reduced the biomass of established biofilms relative to that of the controls. Area layer analysis of biofilms posttreatment indicated that disruption of biomass occurs down to the substratum. Only nanomolar to micromolar concentrations of EIP and H2O2 were required to impact biofilm formation or disruption, and these concentrations are significantly lower than those causing bactericidal effects on planktonic bacteria. Micromolar concentrations of EIP and H2O2 combined enhanced P. aeruginosa swimming motility compared to the effect of either EIP or H2O2 alone. Collectively, our results suggest that the combination of EIP and H2O2 may affect biofilms by interfering with bacterial attachment and destabilizing the biofilm matrix. PMID- 27401563 TI - Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae. AB - Solithromycin (CEM-101) is a "fourth-generation" macrolide, as it has three binding site and is acid stable. The three binding sites confer activity against bacteria resistant to the older macrolides and ketolides, including multidrug resistant Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi). The objective of this study was to evaluate solithromycin pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of experimental otitis media (EOM) due to strains of S. pneumoniae or NTHi. Plasma PK (maximum concentration of drug in serum [Cmax] and area under the concentration-time curve from 0 to 24 h [AUC0-24]) and middle ear fluid (MEF) concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy. Solithromycin administered at 150 mg/kg of body weight/day resulted in Cmax and AUC0-24 values of 2.2 MUg/ml and 27.4 MUg . h/ml in plasma and 1.7 MUg/ml and 28.2 MUg . h/ml in extracellular MEF on day 1. By day 3, Cmax and AUC0-24 values had increased to 4.5 MUg/ml and 54 MUg . h/ml in plasma and 4.8 MUg/ml and 98.6 MUg . h/ml in extracellular MEF. For NTHi EOM, three isolates with MIC/minimal bactericidal concentration (MBC) ratios of 0.5/1 MUg/ml (isolate BCH1), 2/2 MUg/ml (isolate BMC1247C), and 4/4 MUg/ml (isolate BMC1213C) were selected. The MEF of >85% of animals infected with BCH1 and BMC1247C was sterilized. For NTHi BMC1213, >85% of MEF cultures remained positive. For S. pneumoniae EOM, 3 isolates with MIC/MBC ratios of 0.06/0.125 MUg/ml (S. pneumoniae 331), 0.125/1 MUg/ml (S. pneumoniae CP-645 [MLSB phenotype]), and 0.5/2 MUg/ml (CP-712 [mefA subclass mefA resistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected with S. pneumoniae 331 and S. pneumoniae CP-645. ME infection persisted in 60% of animals infected with CP-712. In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with an MIC of <=2 MUg/ml and 100% of ME infected with S. pneumoniae with an MIC of <=0.125 MUg/ml. PMID- 27401564 TI - Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 Grams. AB - Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize the population pharmacokinetics (PK) and dosing requirements of fluconazole in infants with birth weights of <750 g. As part of a randomized clinical trial, infants born at <750 g birth weight received intravenous (i.v.) or oral fluconazole at 6 mg/kg of body weight twice weekly. Fluconazole plasma concentrations from samples obtained by either scheduled or scavenged sampling were measured using a liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using NONMEM 7.2. Population PK parameters were allometrically scaled by body weight. Covariates were evaluated by univariable screening followed by multivariable assessment. Fluconazole exposures were simulated in premature infants using the final PK model. A population PK model was developed from 141 infants using 604 plasma samples. Plasma fluconazole PK were best described by a one-compartment model with first-order elimination. Only serum creatinine was an independent predictor for clearance in the final model. The typical population parameter estimate for oral bioavailability in the final model was 99.5%. Scavenged samples did not bias the parameter estimates and were as informative as scheduled samples. Simulations indicated that the study dose maintained fluconazole troughs of >2,000 ng/ml in 80% of simulated infants at week 1 and 59% at week 4 of treatment. Developmental changes in fluconazole clearance are best predicted by serum creatinine in this population. A twice-weekly dose of 6 mg/kg achieves appropriate levels for prevention of invasive candidiasis in extremely premature infants. PMID- 27401565 TI - Impact of Time to Appropriate Therapy on Mortality in Patients with Vancomycin Intermediate Staphylococcus aureus Infection. AB - Despite the increasing incidence of vancomycin-intermediate Staphylococcus aureus (VISA) infections, few studies have examined the impact of delay in receipt of appropriate antimicrobial therapy on outcomes in VISA patients. We examined the effects of timing of appropriate antimicrobial therapy in a cohort of patients with sterile-site methicillin-resistant S. aureus (MRSA) and VISA infections. In this single-center, retrospective cohort study, we identified all patients with MRSA or VISA sterile-site infections from June 2009 to February 2015. Clinical outcomes were compared according to MRSA/VISA classification, demographics, comorbidities, and antimicrobial treatment. Thirty-day all-cause mortality was modeled with Kaplan-Meier curves. Multivariate logistic regression analysis (MVLRA) was used to determine odds ratios for mortality. We identified 354 patients with MRSA (n = 267) or VISA (n = 87) sterile-site infection. Fifty-five patients (15.5%) were nonsurvivors. Factors associated with mortality in MVLRA included pneumonia, unknown source of infection, acute physiology and chronic health evaluation (APACHE) II score, solid-organ malignancy, and admission from skilled care facilities. Time to appropriate antimicrobial therapy was not significantly associated with outcome. Presence of a VISA infection compared to that of a non-VISA S. aureus infection did not result in excess mortality. Linezolid use was a risk for mortality in patients with APACHE II scores of >=14. Our results suggest that empirical vancomycin use in patients with VISA infections does not result in excess mortality. Future studies should (i) include larger numbers of patients with VISA infections to confirm the findings presented here and (ii) determine the optimal antibiotic therapy for critically ill patients with MRSA and VISA infections. PMID- 27401566 TI - Organic Cation Transporter 2 Overexpression May Confer an Increased Risk of Gentamicin-Induced Nephrotoxicity. AB - Nephrotoxicity is a relevant limitation of gentamicin, and obese patients have an increased risk for gentamicin-induced kidney injury. This damage is thought to depend on the accumulation of the drug in the renal cortex. Obese rats showed substantially higher levels of gentamicin in the kidney than did lean animals. This study characterized the role of organic cation transporters (OCTs) in gentamicin transport and elucidated their possible contribution in the increased renal accumulation of gentamicin in obesity. The mRNA and protein expression levels of the organic cation transporters Oct2 (Slc22a2) and Oct3 (Slc22a3) were increased in kidney samples from obese mice fed a high-fat diet. Similarly, OCT2 (~2-fold) and OCT3 (~3-fold) showed increased protein expression in the kidneys of obese patients compared with those of nonobese individuals. Using HEK293 cells overexpressing the different OCTs, human OCT2 was found to transport [(3)H]gentamicin with unique sigmoidal kinetics typical of homotropic positive cooperativity (autoactivation). In mouse primary proximal tubular cells, [(3)H]gentamicin uptake was reduced by approximately 40% when the cells were coincubated with the OCT2 substrate metformin. The basolateral localization of OCT2 suggests that gentamicin can enter proximal tubular cells from the blood side, probably as part of a slow tubular secretion process that may influence intracellular drug concentrations and exposure time. Increased expression of OCT2 may explain the higher accumulation of gentamicin, thereby conferring an increased risk of renal toxicity in obese patients. PMID- 27401567 TI - In Vitro and In Vivo Synergy of the Oxadiazole Class of Antibacterials with beta Lactams. AB - The oxadiazole antibacterials target the bacterial cell wall and are bactericidal. We investigated the synergism of ND-421 with the commonly used beta lactams and non-beta-lactam antibiotics by the checkerboard method and by time kill assays. ND-421 synergizes well with beta-lactam antibiotics, and it also exhibits a long postantibiotic effect (4.7 h). We also evaluated the in vivo efficacy of ND-421 in a murine neutropenic thigh infection model alone and in combination with oxacillin. ND-421 has in vivo efficacy by itself in a clinically relevant infection model (1.49 log10 bacterial reduction for ND-321 versus 0.36 log10 for linezolid with NRS119) and acts synergistically with beta-lactam antibiotics in vitro and in vivo, and the combination of ND-421 with oxacillin is efficacious in a mouse neutropenic thigh methicillin-resistant Staphylococcus aureus (MRSA) infection model (1.60 log10 bacterial reduction). The activity of oxacillin was potentiated in the presence of ND-421, as the strain would have been resistant to oxacillin otherwise. PMID- 27401568 TI - Detection of mcr-1 among Escherichia coli Clinical Isolates Collected Worldwide as Part of the SENTRY Antimicrobial Surveillance Program in 2014 and 2015. PMID- 27401569 TI - Intermittent Preventive Treatment with Dihydroartemisinin-Piperaquine in Ugandan Schoolchildren Selects for Plasmodium falciparum Transporter Polymorphisms That Modify Drug Sensitivity. AB - Dihydroartemisinin-piperaquine (DP) offers prolonged protection against malaria, but its impact on Plasmodium falciparum drug sensitivity is uncertain. In a trial of intermittent preventive treatment in schoolchildren in Tororo, Uganda, in 2011 to 2012, monthly DP for 1 year decreased the incidence of malaria by 96% compared to placebo; DP once per school term offered protection primarily during the first month after therapy. To assess the impact of DP on selection of drug resistance, we compared the prevalence of key polymorphisms in isolates that emerged at different intervals after treatment with DP. Blood obtained monthly and at each episode of fever was assessed for P. falciparum parasitemia by microscopy. Samples from 160 symptomatic and 650 asymptomatic episodes of parasitemia were assessed at 4 loci (N86Y, Y184F, and D1246Y in pfmdr1 and K76T in pfcrt) that modulate sensitivity to aminoquinoline antimalarials, utilizing a ligase detection reaction-fluorescent microsphere assay. For pfmdr1 N86Y and pfcrt K76T, but not the other studied polymorphisms, the prevalences of mutant genotypes were significantly greater in children who had received DP within the past 30 days than in those not treated within 60 days (86Y, 18.0% versus 8.3% [P = 0.03]; 76T, 96.0% versus 86.1% [P = 0.05]), suggesting selective pressure of DP. Full sequencing of pfcrt in a subset of samples did not identify additional polymorphisms selected by DP. In summary, parasites that emerged soon after treatment with DP were more likely than parasites not under drug pressure to harbor pfmdr1 and pfcrt polymorphisms associated with decreased sensitivity to aminoquinoline antimalarials. (This study has been registered at ClinicalTrials.gov under no. NCT01231880.). PMID- 27401570 TI - Detectable Tenofovir Levels in Breast-Feeding Infants of Mothers Exposed to Topical Tenofovir. AB - Lactation studies are necessary evaluations of medications for reproductive-age women. We evaluated pharmacokinetics (PK), pharmacodynamics, safety, and adherence profiles associated with 7 days of 1% tenofovir (TFV) vaginal gel use during lactation. Tenofovir levels (maternal/infant serum, milk) and anti-HIV activity (milk), adverse events (AEs), and adherence were measured for 17 HIV-1 seronegative breast-feeding mother-infant pairs. Tenofovir use was well-tolerated and detected at low levels in maternal serum, milk, and infant serum but demonstrated no anti-HIV activity in milk. PMID- 27401572 TI - Nonprescription Antimicrobial Use in a Primary Care Population in the United States. AB - Community antimicrobial resistance rates are high in communities with frequent use of nonprescription antibiotics. Studies addressing nonprescription antibiotic use in the United States have been restricted to Latin American immigrants. We estimated the prevalence of nonprescription antibiotic use in the previous 12 months as well as intended use (intention to use antibiotics without a prescription) and storage of antibiotics and examined patient characteristics associated with nonprescription use in a random sample of adults. We selected private and public primary care clinics that serve ethnically and socioeconomically diverse patients. Within the clinics, we used race/ethnicity stratified systematic random sampling to choose a random sample of primary care patients. We used a self-administered standardized questionnaire on antibiotic use. Multivariate regression analysis was used to identify independent predictors of nonprescription use. The response rate was 94%. Of 400 respondents, 20 (5%) reported nonprescription use of systemic antibiotics in the last 12 months, 102 (25.4%) reported intended use, and 57 (14.2%) stored antibiotics at home. These rates were similar across race/ethnicity groups. Sources of antibiotics used without prescriptions or stored for future use were stores or pharmacies in the United States, "leftover" antibiotics from previous prescriptions, antibiotics obtained abroad, or antibiotics obtained from a relative or friend. Respiratory symptoms were common reasons for the use of nonprescription antibiotics. In multivariate analyses, public clinic patients, those with less education, and younger patients were more likely to endorse intended use. The problem of nonprescription use is not confined to Latino communities. Community antimicrobial stewardship must include a focus on nonprescription antibiotics. PMID- 27401571 TI - Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine. AB - Lamivudine is one of the antiretroviral drugs of choice for the prevention of mother-to-child transmission (MTCT) in HIV-positive women. In this study, we investigated the relevance of drug efflux transporters P-glycoprotein (P-gp) (MDR1 [ABCB1]), BCRP (ABCG2), MRP2 (ABCC2), and MATE1 (SLC47A1) for the transmembrane transport and transplacental transfer of lamivudine. We employed in vitro accumulation and transport experiments on MDCK cells overexpressing drug efflux transporters, in situ-perfused rat term placenta, and vesicular uptake in microvillous plasma membrane (MVM) vesicles isolated from human term placenta. MATE1 significantly accelerated lamivudine transport in MATE1-expressing MDCK cells, whereas no transporter-driven efflux of lamivudine was observed in MDCK MDR1, MDCK-MRP2, and MDCK-BCRP monolayers. MATE1-mediated efflux of lamivudine appeared to be a low-affinity process (apparent Km of 4.21 mM and Vmax of 5.18 nmol/mg protein/min in MDCK-MATE1 cells). Consistent with in vitro transport studies, the transplacental clearance of lamivudine was not affected by P-gp, BCRP, or MRP2. However, lamivudine transfer across dually perfused rat placenta and the uptake of lamivudine into human placental MVM vesicles revealed pH dependency, indicating possible involvement of MATE1 in the fetal-to-maternal efflux of the drug. To conclude, placental transport of lamivudine does not seem to be affected by P-gp, MRP2, or BCRP, but a pH-dependent mechanism mediates transport of lamivudine in the fetal-to-maternal direction. We suggest that MATE1 might be, at least partly, responsible for this transport. PMID- 27401573 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27401574 TI - Evaluation of Antibiotics Active against Methicillin-Resistant Staphylococcus aureus Based on Activity in an Established Biofilm. AB - We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS 1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when tested in vivo in a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associated S. aureus infections, including by the matrix based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections. PMID- 27401575 TI - mcr-1.2, a New mcr Variant Carried on a Transferable Plasmid from a Colistin Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512. AB - A novel mcr variant, named mcr-1.2, encoding a Gln3-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr 1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa). PMID- 27401576 TI - Critical Role of Alpha-Toxin and Protective Effects of Its Neutralization by a Human Antibody in Acute Bacterial Skin and Skin Structure Infections. AB - Methicillin-resistant Staphylococcus aureus (MRSA) causes large-scale epidemics of acute bacterial skin and skin structure infections (ABSSSI) within communities across the United States. Animal models that reproduce ABSSSI as they occur in humans are urgently needed to test new therapeutic strategies. Alpha-toxin plays a critical role in a variety of staphylococcal infection models in mice, but its role in the pathogenesis of ABSSSI remains to be elucidated in rabbits, which are similar to humans in their susceptibility to S. aureus superantigens and certain bicomponent pore-forming leukocidins. We report here a new rabbit model of ABSSSI and show that those infected with a mutant deficient in expression of alpha-toxin (Deltahla) developed a small dermonecrotic lesion, whereas those infected with isogenic USA300 MRSA wild-type or complemented Deltahla strains developed ABSSSI that mimic the severe infections that occur in humans, including the large central dermonecrotic core surrounded by erythema, induration, and marked subcutaneous hemorrhage. More importantly, immunoprophylaxis with MEDI4893*, an anti-alpha-toxin human monoclonal antibody, significantly reduced the severity of disease caused by a USA300 wild-type strain to that caused by the Deltahla mutant, indicating that this toxin could be completely neutralized during infection. Thus, this study illustrates a potential high standard for the development of new immunotherapeutic agents in which a toxin-neutralizing antibody provides protection to the same degree achieved with a toxin gene knockout. When MEDI4893* was administered as adjunctive therapy with a subtherapeutic dose of linezolid, the combination was significantly more efficacious than either agent alone in reducing the severity of ABSSSI. PMID- 27401577 TI - Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms. AB - It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new antibiotic development programs by the pharmaceutical industries, drug repurposing is an attractive alternative. In this work, we screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against Staphylococcus aureus, one of the commonly encountered causative pathogens of burn and wound infections. From the primary screen of the entire Prestwick Chemical Library at a fixed concentration of 10 MUM, 104 drugs were found to be effective against planktonic S. aureus strains, and not surprisingly, these were mostly antimicrobials and antiseptics. The activity of 18 selected repurposing candidates, that is, drugs that show antimicrobial activity that are not already considered antimicrobials, observed in the primary screen was confirmed in dose-response experiments. Finally, a subset of nine of these drug candidates was tested against preformed biofilms of S. aureus We found that three of these drugs, niclosamide, carmofur, and auranofin, possessed antimicrobial activity against preformed biofilms, making them attractive candidates for repurposing as novel antibiofilm therapies. PMID- 27401578 TI - Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin. AB - Aspergillus fumigatus can infect immunocompromised patients, leading to high mortality rates due to the lack of reliable treatment options. This pathogen requires uptake of zinc from host tissues in order to successfully grow and cause virulence. Reducing the availability of that micronutrient could help treat A. fumigatus infections. In this study, we examined the in vitro effects of seven chelators using a bioluminescent strain of A. fumigatus 1,10-Phenanthroline and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) proved to be the chelators most effective at inhibiting fungal growth. Intraperitoneal administration of either phenanthroline or TPEN resulted in a significant improvement in survival and decrease of weight loss and fungal burden for immunosuppressed mice intranasally infected with A. fumigatus In vitro both chelators had an indifferent effect when employed in combination with caspofungin. The use of TPEN in combination with caspofungin also significantly increased survival compared to that when using these drugs individually. Our results suggest that zinc chelation may be a valid strategy for dealing with A. fumigatus infections and that both phenanthroline and TPEN could potentially be used either independently or in combination with caspofungin, indicating that their use in combination with other antifungal treatments might also be applicable. PMID- 27401579 TI - Molecular Epidemiology of a Vancomycin-Intermediate Heteroresistant Staphylococcus epidermidis Outbreak in a Neonatal Intensive Care Unit. AB - Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV) Staphylococcus epidermidis central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak. Between November 2009 and April 2014, 119 S. epidermidis CLABSIs were identified in two tertiary care NICUs in Quebec, Canada. Decreased vancomycin susceptibility was identified in about 88% of all collected strains using Etest methods. However, discrepancies were found according to the Etest and population analysis profiling-area under the concentration-time curve (PAP-AUC) methods used. All strains were susceptible to linezolid, and a few isolates were nonsusceptible to daptomycin. Great genetic diversity was observed within the collection, with 31 pulsed-field gel electrophoresis (PFGE) patterns identified. The outbreak strains were all determined to be heteroresistant to vancomycin and were polyclonal. The study identified two major clones, PFGE patterns E and G, which were found in both NICUs across the 5-year study period. This suggests the persistence of highly successful clones that are well adapted to the hospital environment. hV S. epidermidis seems more common than currently realized in the NICU, and certain hV S. epidermidis clones can become endemic to the NICU. The reservoirs for these clones remain unknown at this time, and identification of the reservoirs is needed to better understand the impact of hV S. epidermidis in the NICU and to inform infection prevention strategies. In addition, there is a need to investigate and validate hV determination protocols for different species of CoNS. PMID- 27401580 TI - Impact of Infectious Diseases Consultation on Clinical Outcomes of Patients with Staphylococcus aureus Bacteremia in a Community Health System. AB - Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited settings such as community hospitals are available. This retrospective cohort study evaluated the adherence to quality-of-care indicators and the clinical outcomes for SAB in a five-hospital community health system (range of 95 to 272 available beds per hospital), for patients with versus without infectious diseases consultation (IDC). IDC was provided if requested by the attending physician. The primary outcome was the incidence of treatment failure, defined as 30-day in hospital death or 90-day SAB recurrence. Other outcomes included adherence to quality-of-care indicators. A total of 473 adult patients with SAB were included, with 369 (78%) receiving IDC. We identified substantial differences in baseline characteristics between the IDC group and the no-IDC group, including greater incidences of complicated bacteremia and intravenous drug users in the IDC group, with similar rates of severe illness (measured by Pitt bacteremia scores). Adherence to quality-of-care indicators was greater for patients with IDC (P < 0.001). After adjustment for other predicting variables, IDC was associated with a lower rate of treatment failure (adjusted odds ratio, 0.42 [95% confidence interval, 0.20 to 0.86]; P = 0.018). IDC provided better quality of care and better clinical outcomes for patients with SAB who were treated at small, resource-limited, community hospitals. PMID- 27401581 TI - Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study. AB - BACKGROUND: The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. METHODS: In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. RESULTS: Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. CONCLUSION: In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation. PMID- 27401582 TI - Early Perspective. AB - The cellular thermal shift assay (CETSA) was introduced in 2013 as a means to assess drug binding in complex environments such as cell lysates, live cells, and even tissues. The assay principle relies on the well-proven biophysical concept of ligand-induced thermal stabilization of proteins, which in CETSA applications is measured as a persistent presence of soluble protein at elevated temperatures. Given its recent development, we have just started to learn about the benefits and pitfalls of the method as it is applied to a growing number of protein target classes, the majority of which are intracellular soluble proteins. One of the early technology developments concerned the transfer of the original assay procedure from PCR tubes and Western blot detection of soluble protein to a homogeneous assay in high-density microplates. A move to high-throughput formats is essential for a more systematic application in drug discovery settings, as well as in academic efforts for validating chemical probes through studies of structure-activity relationships. This perspective aims at providing an overview of knowledge gained in microplate formatting of CETSA and makes an attempt at forecasting future applications. PMID- 27401583 TI - Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors. AB - The breast cancer resistance protein (BCRP) is an ABC transporter playing a crucial role in the pharmacokinetics of drugs. The early identification of substrates and inhibitors of this efflux transporter can help to prevent or foresee drug-drug interactions. In this work, we built a ligand-based in silico classification model to predict the inhibitory potential of drugs toward BCRP. The model was applied as a virtual screening technique to identify potential inhibitors among the small-molecules subset of DrugBank. Ten compounds were selected and tested for their capacity to inhibit mitoxantrone efflux in BCRP expressing PLB985 cells. Results identified cisapride (IC50 = 0.4 uM) and roflumilast (IC50 = 0.9 uM) as two new BCRP inhibitors. The in silico strategy proved useful to prefilter potential drug-drug interaction perpetrators among a database of small molecules and can reduce the amount of compounds to test. PMID- 27401584 TI - The additional yield of GeneXpert MTB/RIF test in the diagnosis of pulmonary tuberculosis among household contacts of smear positive TB cases. AB - OBJECTIVE: The objective of this study was to compare the diagnostic yield of GeneXpert MTB/RIF with Ziehl-Neelson (ZN) sputum smear microscopy among index TB cases and their household contacts. METHODS: A cross sectional study was conducted among sputum smear positive index TB cases and their household contacts in Northern Ethiopia. RESULTS: Of 353 contacts screened, 41 (11%) were found to have presumptive TB. GeneXpert test done among 39 presumptive TB cases diagnosed 14 (35.9%) cases of TB (one being rifampicin resistant), whereas the number of TB cases diagnosed by microscopy was only 5 (12.8%): a 64.3% increased positivity rate by GeneXpert versus ZN microscopy. The number needed to screen and number needed to test to diagnose a single case of TB was significantly lower with the use of GeneXpert than ZN microscopy. Of 119 index TB cases, GeneXpert test revealed that 106 (89.1%) and 5 (4.2%) were positive for rifampicin sensitive and rifampicin resistant TB, respectively. CONCLUSION: GeneXpert test led to increased TB case detection among household contacts in addition to its advantage in the diagnosis of Rifampicin resistance among contacts and index TB cases. There should be a consideration in using GeneXpert MTB/RIF as a point of care TB testing tool among high risk groups. PMID- 27401585 TI - High Oral Carriage of Non-albicans Candida spp. among HIV-infected individuals. AB - BACKGROUND: Non-albicans Candida (NAC) spp. in immunocompromised patients are linked to invasive infections with narrow treatment choice. This study aimed at comparing the oral colonization of NAC spp. between HIV and non-HIV infected individuals in Mwanza, Tanzania. METHOD: Oral rinse of 351 HIV-infected and 639 non-HIV infected individuals were collected between March and July 2015. Phenotypic identifications of Candida spp. was done using Candida Chromogenic agar and confirmed by MALDI-TOF MS. RESULTS: NAC spp. were detected in 36/351 (10.3%) HIV-infected individuals compared to 28/639 (4.4%) of non-HIV infected individuals; P=0.0003. In HIV infected individuals, commonly isolated NAC spp. were Candida tropicalis, 10(2.8%), C. krusei (Issatschenki orientalis) 9(2.6%) and C. glabrata 8(2.3%). While for non-HIV infected individuals C. dubliniensis 8(1.3%) and C. tropicalis 5(0.9%) were commonly detected. As CD4 count/MUl decreases by one unit the risk of being colonized by NAC spp. among HIV infected individuals increases by 1% (OR 1.01, 95% CI; 1.001-1.004, P=0.001). CONCLUSION: The prevalence of NAC spp. is high among HIV-infected individuals with low CD4 count placing them at higher risk of invasive infections. Further studies to investigate the role of NAC spp. in causing invasive infections among immunocompromised patients are recommended. PMID- 27401587 TI - Metastatic amelanotic melanomas showing spontaneous regression after skin biopsies. PMID- 27401586 TI - Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C. AB - BACKGROUND: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. MATERIALS AND METHODS: 178 antiviral-naive patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. RESULTS: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. CONCLUSION: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment. PMID- 27401588 TI - Effects of the levonorgestrel-releasing intrauterine device on the immune microenvironment of the human cervix and endometrium. AB - PROBLEM: There is little information regarding the impact of the intrauterine device on immune parameters of the upper female reproductive tract related to risk of HIV acquisition. METHOD OF STUDY: We collected cervical and endometrial samples from women using the hormonal intrauterine device to study its effects on endocervical cytokines/chemokine concentrations, phenotypic markers of T cells, responses of endometrial T cells to activation, and alterations of endometrial cellular infiltrates. RESULTS: Hormonal intrauterine device use was associated with: increased concentrations of inflammatory cytokines/chemokines (endocervix); increased coexpression of CXCR4 and CCR5 (endocervix and endometrium); increased coexpression of CD38 and HLADR (endocervix and endometrium); increased intracellular IL-10 production after T-cell stimulation (endometrium); and increased density of T cells, most notably regulatory T cells (endometrium). CONCLUSION: Hormonal intrauterine device use resulted in both inflammatory and immunosuppressive alterations. Further research is needed to determine the significance of these changes for HIV risk. PMID- 27401590 TI - Association of interleukin-10 gene promoter polymorphisms with recurrent miscarriage: a meta-analysis. AB - PROBLEM: The association between IL-10 gene promoter polymorphisms and the risk of recurrent miscarriages (RM) remains controversial. The present meta-analysis was performed to derive a precise estimate of the relationship. METHOD OF STUDY: We searched the PubMed and EMBASE for studies related to the association between the IL-10 gene polymorphism and the risk of RM. Summary odds ratio (OR) with 95% confidence interval (CI) was estimated to assess the associations. RESULTS: Thirteen studies, including 2047 RM cases and 2055 control samples, were identified. The results showed a significant association between rs1800896, rs1800871 and RM risk (for rs1800896: GA+GG vs AA: OR=1.20, 95% CI=1.04-1.39, P=.02; for rs1800871: CT+TT vs CC: OR=1.64, 95% CI=1.13-2.36, P=.009). No evidence of association was noted between rs1800872 haplotype and RM risk. CONCLUSION: IL-10 gene promoter polymorphisms, rs1800896 and rs1800871, play a potential role in increasing the risk of RM. PMID- 27401589 TI - Inherited thrombophilia in women with poor aPL-related obstetric history: prevalence and outcomes. Survey of 208 cases from the European Registry on Obstetric Antiphospholipid Syndrome cohort. AB - AIM: To analyse the prevalence and effects of inherited thrombophilic disorders (ITD) on maternal-foetal outcomes in cases of antiphospholipid antibody related to obstetric complications. METHODS: Women with obstetric complaints who tested positive for aPL and with inherited thrombophilia were prospectively and retrospectively included. RESULTS: ITD data were available in 208 of 338: 147 had obstetric antiphospholipid syndrome (OAPS) and 61 aPL-related obstetric morbidity (OMAPS). 24.1% had ITD. Laboratory categories I and IIa were more related to OAPS ITD and IIb and IIc to OMAPS-ITD. No significant differences in obstetric complaints were observed. Regarding ITD carriers, treatment rates were higher in OAPS than in OMAPS for LMWH and LDA plus LMWH (P=.002). CONCLUSION: Cases with aPL-related OAPS/OMAPS showed no differences in maternal-foetal outcomes regardless of the presence of one ITD. Maternal thrombotic risk was low, with ITD positive cases included. Registry data concur with Sydney criteria, whereby aPL ITD-positive patients are classified as having antiphospholipid syndrome. PMID- 27401592 TI - Angiotensin-converting enzyme inhibitor-induced angioedema worsened with fresh frozen plasma. PMID- 27401591 TI - Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers. AB - Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes of compounds reported by FDA to be significant contributors to smoking associated disease risks were measured in 105 clinical-confined subjects following randomization and a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use of commercial e-cigarettes and the subject's usual cigarette brand; or (iii) discontinued use of all tobacco or nicotine products. Levels of urinary biomarkers in subjects that completely substituted their usual cigarette with e cigarettes were significantly lower (29-95%) after 5 days. Percent reductions in eight of nine urinary BoEs were indistinguishable to smokers who had quit smoking, except for nicotine equivalents, which declined by 25-40%. Dual users who halved self-reported daily cigarette consumption with e-cigarettes exhibited reductions (7-38%) in eight of nine urinary biomarkers, but had increase (1-20%) in nicotine equivalents. Reductions were broadly proportional to the reduced numbers of cigarettes smoked. Dual user urinary nicotine equivalents were slightly higher, but not statistically significant. After 5 days, blood nicotine biomarker levels were lower in the cessation (75-96%) and exclusive use groups (11-83%); with dual users experiencing no significant reductions. All subjects experienced significant decreases in exhaled CO. Decreases in the cessation and exclusive groups ranged from 88-89% and 27-32% in dual users. Exhaled NO increased in the cessation and exclusive groups (46-63% respectively), whereas the dual users experienced minimal changes. Overall, smokers who completely or partially substituted conventional cigarettes with e-cigarettes over five days, experienced reductions in HPHCs. PMID- 27401593 TI - Low-dose intravenous propofol as a possible therapeutic option for acute confusional migraine. PMID- 27401594 TI - Salvage of upper extremity in an aggressive case of Pasteurella multocida infection. PMID- 27401595 TI - Strain sonoelastography of inflammatory myopathies: comparison with clinical examination, magnetic resonance imaging and pathologic findings. AB - OBJECTIVE: To evaluate strain sonoelastography (SSE) in patients with inflammatory myopathies (IM) compared with clinical examination, MRI and pathologic findings. METHODS: 18 lesions from 17 consecutive patients with IM (5 males and 12 females; mean age, 41.2 years; range, 11-67 years) were assessed with SSE after MRI. The ratio of strain in the target muscle (A) and a nearby normal muscle (B), defined as the strain index value (SR) (B/A), was calculated automatically. Elastograms were assigned an elasticity score according to the degree and distribution of strain induced by manual compression. Ultrasonography and MRI were analyzed in conjunction with clinical information, biochemical data, final clinical diagnosis and grading of pathology. Correlations between SR and qualitative analyses of MRI and ultrasonography, elasticity score, biochemical data and final clinical diagnosis were analyzed using Pearson's correlation coefficient. RESULTS: The SR of the target muscles was high in patients with IM (mean 3.14; range, 0.95-5.93 +/- 1.42). The correlations between SR and pathologic grading and elasticity score were statistically significant (p < 0.05). There was no significant agreement between SR and other clinical and radiologic parameters. CONCLUSION: Muscle hardness, as semi-quantitatively measured by SSE, was increased in cases of IM. The correlation between the SR and the pathologic grading suggests that SSE could be an important tool in not only the diagnosis of but also in measuring the degree of muscular inflammation. ADVANCES IN KNOWLEDGE: This work describes a correlation between tissue elasticity and pathology in IM. PMID- 27401598 TI - Inter-rater reliability of the Reaper Oral Mucosa Pressure Injury Scale (ROMPIS): A novel scale for the assessment of the severity of pressure injuries to the mouth and oral mucosa. AB - BACKGROUND: Patients who are intubated in the ICU are at risk of developing pressure injuries to the mouth and lips from endotracheal tubes. Clear documentation is important for pressure wound care; however, no validated instruments currently exist for the staging of pressure injuries to the oral mucosa. Instruments designed for the assessment of pressure injuries to other bodily regions are anatomically unsuited to the lips and mouth. OBJECTIVES: This study aimed to develop and then assess the reliability of a novel scale for the assessment of pressure injuries to the mouth and oral mucosa. METHODS: The Reaper Oral Mucosa Pressure Injury Scale (ROMPIS) was developed in consultation with ICU nurses, clinical nurse educators, Intensivists, and experts in pressure wound management. ICU nurses and portfolio-holders in pressure wound care from Peninsula Health (Victoria, Australia) were invited to use the ROMPIS to stage 19 de-identified clinical photographs of oral pressure injuries via secure online survey. Inter-rater reliability (IRR) was calculated using Krippendorff's alpha (alpha). RESULTS: Among ICU nurses (n=52), IRR of the ROMPIS was alpha=0.307; improving to alpha=0.463 when considering only responses where injuries were deemed to be stageable using the ROMPIS (i.e. excluding responses where respondents considered an injury to be unstageable). Among a cohort of experts in pressure wound care (n=8), IRR was alpha=0.306; or alpha=0.443 excluding responses indicating that wounds were unstageable. CONCLUSIONS: An instrument for the assessment and monitoring of pressure injuries to the mouth and lips has practical implications for patient care. This preliminary study indicates that the ROMPIS instrument has potential to be used clinically for this purpose; however, the performance of this scale may be somewhat reliant on the confidence or experience of the ICU nurse utilising it. Further validation is required. PMID- 27401597 TI - Potential Implications of Recent and Proposed Changes in the Regulatory Oversight of Solid Organ Transplantation in the United States. AB - Every 6 months, the Scientific Registry of Transplant Recipients (SRTR) publishes evaluations of every solid organ transplant program in the United States, including evaluations of 1-year patient and graft survival. The Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network (OPTN) Membership and Professional Standards Committee (MPSC) use SRTR's 1-year evaluations for regulatory review of transplant programs. Concern has been growing that the regulatory scrutiny of transplant programs with lower-than expected outcomes is harmful, causing programs to undertake fewer high-risk transplants and leading to unnecessary organ discards. As a result, CMS raised its threshold for a "Condition-Level Deficiency" designation of observed relative to expected 1-year graft or patient survival from 1.50 to 1.85. Exceeding this threshold in the current SRTR outcomes report and in one of the four previous reports leads to scrutiny that may result in loss of Medicare funding. For its part, OPTN is reviewing a proposal from the MPSC to also change its performance criteria thresholds for program review, to review programs with "substantive clinical differences." We review the details and implications of these changes in transplant program oversight. PMID- 27401599 TI - Assessment of Heavy-Metal Pollution in Sediments and Tilapia Fish Species in Kafue River of Zambia. AB - We report results from an evaluation of the levels of heavy metals, i.e., copper (Cu), cadmium (Cd), lead (Pb), nickel (Ni), manganese (Mn), chromium (Cr), and iron (Fe) in sediment and tilapia fish samples from a wide stretch of the Kafue river of Zambia. In sediment samples, the highest Pb and Fe concentrations were recorded at Hippo Dam, i.e., 36.2 +/- 0.1 mg/kg dw and 733 +/- 37 mg/kg dw at Kafue Town, respectively. Other notably high metal concentrations in sediment were Cr at Kafue Bridge (42.5 +/- 0.1 mg/kg dw [dw]), Cu at Mpongwe (233 +/- 5 mg/kg dw), and Mn at Kafue Town (133 +/- 1 mg/kg dw); it was highest at Ithezi Tezhi Dam at 166 +/- 1 mg/kg d. Three fish species, i.e., three-spot bream Tilapia andersonii, red-breasted bream T. rendalli, and nile tilapia Oreochromis niloticus were evaluated for levels of the seven metals. The concentrations of the metals in these fish species afforded estimation of the biota sediment accumulation factor, which is the ratio of the concentration of the metal in liver to that in the sediment. The coefficients of condition (K) values, which give an indication of the health of the fish, were also estimated. The K values ranged from 2.5 +/- 0.5 to 5.1 +/- 0.6 in all of the three fish species. Partial least squares analysis showed that heavy metals are generally sequestered evenly in all of the parts of all of the three fish species except for elevated levels of Mn, Cd, and Pb in the liver samples. PMID- 27401600 TI - Water sorption behaviour of two series of PHA/montmorillonite films and determination of the mean water cluster size. AB - Biodegradable polyester-based films constituted of poly(hydroxyalkanoates) (PHA) were successfully extruded with various Cloisite 30B contents. The morphology was highly dependent on the matrix, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), the polymer crystalline phase fraction, the matrix/nanoclay interfacial regions as well as the nanoclay content. Water vapour resistance was investigated through sorption kinetics, isotherms, modelling aspect, and diffusivity. A typical sigmoid-shaped isotherm was obtained in every case. It emerges that the nanoclay highly contributed to the increase of water solubility of matrices. The dependence of polymer crystallinity on the affinity of the nanocomposite films for water was highlighted. Thermodynamic and kinetic contributions of the sorption process were also correlated with the film morphology. According to the matrix used, water diffusivity in films was differently impacted by the sorbed water amount. The access of sorbed water molecules within films was examined through a mathematical modelling approach and the deduced mean cluster size of water vs. its activity was corroborated by sorption kinetics. PMID- 27401601 TI - Novel strategies for discovering inhibitors of Dengue and Zika fever. PMID- 27401602 TI - Takotsubo cardiomyopathy: serious early complications and two-year mortality - a 101 case study. AB - BACKGROUND: Takotsubo cardiomyopathy (TTC) is characterised by transient contractility disturbances of the apex of the left ventricle. METHODS: We enrolled 101 patients from the northern-eastern part of Poland in the years 2008 2012 who were hospitalised for TCC. The control group consisted of female patients diagnosed with anterior myocardial infarction with ST-segment elevation (anterior STEMI) (n = 101). RESULTS: 89 % of the study group were women. Patients with TTC had diabetes (12.6 % vs 29.7 %; p = 0.002) and hyperlipidaemia (36.8 % vs 64.4 %; p = 0.0001) significantly less frequently, and better kidney function assessed by estimated glomerular filtration rate versus patients with anterior STEMI (74.52 % vs 64.30 %; p = 0.004). In the TTC group there were more patients with chronic obstructive pulmonary disease (11.6 % vs 1.0 %; p = 0.002) and thyroid disturbances, especially hyperthyroidism (23.4 % vs 11.0 %; p = 0.021). In patients with TTC sudden cardiac arrest, pulmonary oedema and cardiogenic shock were observed less frequently than in the control group (14.7 % vs 30.7 %; p = 0.0078). Hospitalisations in TTC patients were less frequently complicated by pneumonia (20.0 % vs 35.6 %; p = 0.0148) and urinary infection (4.2 % vs 21.8 %; p = 0.0003). Cardiac rupture occurred in 3 patients with TTC and in 1 with anterior STEMI. In-hospital mortality was significantly lower in the group with TTC. Also, mortality at 30 days, 3 months, 1 year and 2.5 years was significantly lower in patients with TTC than in patients with MI (p = 0.035; p = 0.0226; p = 0.0075; p = 0.009). CONCLUSIONS: Previously considered to be a benign syndrome, TTC should be reconsidered as a clinical condition at risk for serious complications such as cardiac arrest, cardiogenic shock, pulmonary oedema and cardiac rupture leading to death and causing substantial early hazard. The prognosis in TTC is significantly better than in patients with anterior STEMI. PMID- 27401603 TI - Psychological distress and personality factors in takotsubo cardiomyopathy. AB - BACKGROUND: Takotsubo cardiomyopathy (TCC) is a transient condition characterised by severe left ventricular dysfunction combined with symptoms and signs mimicking myocardial infarction. Emotional triggers are common, but little is known about the psychological background characteristics of TCC. This study examined whether patients with TTC have higher levels of psychological distress (depressive symptoms, perceived stress, general anxiety), illness-related anxiety and distinct personality factors compared with healthy controls and patients with heart failure. METHODS AND RESULTS: Patients with TCC (N = 18; mean age 68.3 +/- 11.7 years, 77.8 % women) and two comparison groups (healthy controls: N = 19, age 60.0 +/- 7.6, 68.4 % women and patients with chronic heart failure: N = 19, age 68.8 +/- 10.1, 68.4 % women) completed standardised questionnaires to measure depression (PHQ-9), perceived stress (PSS-10), general anxiety (GAD-7), illness related anxiety (WI-7) and personality factors (NEO-FFI and DS-14). Psychological measures were obtained at 23 +/- 18 months following the acute TTC event. Results showed that patients with TCC had higher levels of depressive symptoms (5.2 +/- 5.2 vs. 2.5 +/- 2.4, p = 0.039) and illness-related anxiety (2.1 +/- 1.7 vs. 0.7 +/- 1.3, p = 0.005) compared with healthy controls. Patients with TCC did not display significantly elevated perceived stress (p = 0.072) or general anxiety (p = 0.170). Regarding personality factors, levels of openness were lower in TCC compared with healthy controls (34.2 +/- 4.3 vs. 38.2 +/- 5.6, p = 0.021). No differences between TCC and heart failure patients were found regarding the psychological measures. CONCLUSIONS: TCC is associated with higher levels of depressive symptoms, more illness-related anxiety and less openness compared with healthy controls. These data suggest that TCC is associated with adverse psychological factors that may persist well after the acute episode. PMID- 27401604 TI - Drug-loaded particles: "Trojan horses" in the therapy of atherosclerosis. PMID- 27401605 TI - Ethnicity, ABO group, endothelial dysfunction and cardiovascular disease: Multiple connections, multiple implications. PMID- 27401606 TI - Integrating data from an online diabetes prevention program into an electronic health record and clinical workflow, a design phase usability study. AB - BACKGROUND: Health information is increasingly being digitally stored and exchanged. The public is regularly collecting and storing health-related data on their own electronic devices and in the cloud. Diabetes prevention is an increasingly important preventive health measure, and diet and exercise are key components of this. Patients are turning to online programs to help them lose weight. Despite primary care physicians being important in patients' weight loss success, there is no exchange of information between the primary care provider (PCP) and these online weight loss programs. There is an emerging opportunity to integrate this data directly into the electronic health record (EHR), but little is known about what information to share or how to share it most effectively. This study aims to characterize the preferences of providers concerning the integration of externally generated lifestyle modification data into a primary care EHR workflow. METHODS: We performed a qualitative study using two rounds of semi-structured interviews with primary care providers. We used an iterative design process involving primary care providers, health information technology software developers and health services researchers to develop the interface. RESULTS: Using grounded-theory thematic analysis 4 themes emerged from the interviews: 1) barriers to establishing healthy lifestyles, 2) features of a lifestyle modification program, 3) reporting of outcomes to the primary care provider, and 4) integration with primary care. These themes guided the rapid cycle agile design process of an interface of data from an online diabetes prevention program into the primary care EHR workflow. CONCLUSIONS: The integration of external health-related data into the EHR must be embedded into the provider workflow in order to be useful to the provider and beneficial for the patient. Accomplishing this requires evaluation of that clinical workflow during software design. The development of this novel interface used rapid cycle iterative design, early involvement by providers, and usability testing methodology. This provides a framework for how to integrate external data into provider workflow in efficient and effective ways. There is now the potential to realize the importance of having this data available in the clinical setting for patient engagement and health outcomes. PMID- 27401607 TI - Celiac disease diagnosis still significantly delayed - Doctor's but not patients' delay responsive for the increased total delay in women. AB - BACKGROUND: There is insufficient data on diagnostic delay and associated factors in celiac disease (CeD) as well as on its potential impact on the course of disease. METHODS: Specifically taking its two components - patients' and doctors' delay - into account, we performed a large systematic patient survey study among unselected CeD patients in Switzerland. RESULTS: We found a mean/median total diagnostic delay of 87/24 months (IQR 5-96), with a range from 0 up to 780 months and roughly equal fractions of patients' and doctors' delay. Both mean/median total (93.1/24 vs. 60.2/12, p<0.001) and doctors' (41.8/3 vs. 23.9/2, p<0.001) diagnostic delay were significantly higher in female vs. male patients, whereas patients' delay was similar, regardless of preceding irritable bowel syndrome diagnosis. Patients with a diagnostic delay shorter than 2 years were significantly less often in need of steroids and/or immunosuppressants, substitution for any nutritional deficiency but more often free of symptoms 6 and 12 months after diagnosis. CONCLUSIONS: There is a substantial diagnostic delay in CeD, which is associated with a worse clinical outcome and significantly longer in female patients. This increased diagnostic delay in women is due to doctors' but not patients' delay and cannot be explained by antecedent IBS prior to establishing the CeD diagnosis. PMID- 27401608 TI - US urges Puerto Rico to start aerial spraying to reduce risk of birth defects. PMID- 27401610 TI - The ambiguous relationship between spikes and seizures. PMID- 27401609 TI - Elasticity mapping of murine abdominal organs in vivo using harmonic motion imaging (HMI). AB - Recently, ultrasonic imaging of soft tissue mechanics has been increasingly studied to image otherwise undetectable pathologies. However, many underlying mechanisms of tissue stiffening remain unknown, requiring small animal studies and adapted elasticity mapping techniques. Harmonic motion imaging (HMI) assesses tissue viscoelasticity by inducing localized oscillation from a periodic acoustic radiation force. The objective of this study was to evaluate the feasibility of HMI for in vivo elasticity mapping of abdominal organs in small animals. Pathological cases, i.e. chronic pancreatitis and pancreatic cancer, were also studied in vivo to assess the capability of HMI for detection of the change in mechanical properties. A 4.5 MHz focused ultrasound transducer (FUS) generated an amplitude-modulated beam resulting in 50 Hz harmonic tissue oscillations at its focus. Axial tissue displacement was estimated using 1D-cross-correlation of RF signals acquired with a 7.8 MHz diagnostic transducer confocally aligned with the FUS. In vitro results in canine liver and kidney showed the correlation between HMI displacement and Young's moduli measured by rheometry compression testing. HMI was capable of providing reproducible elasticity maps of the mouse abdominal region in vivo allowing the identification of, from stiffest to softest, the murine kidney, pancreas, liver, and spleen. Finally, pancreata affected by pancreatitis and pancreatic cancer showed HMI displacements 1.7 and 2.2 times lower than in the control case, respectively, indicating higher stiffness. The HMI displacement amplitude was correlated with the extent of fibrosis as well as detecting the very onset of stiffening even before fibrosis could be detected on H&E. This work shows that HMI can produce reliable elasticity maps of mouse abdominal region in vivo, thus providing a potentially critical tool to assess pathologies affecting organ elasticity. PMID- 27401611 TI - Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma. AB - Growth arrest-specific 1 (Gas1) plays a critical role in growth suppression. Previous study indicated that Gas1 was closely associated with survival in patients with colorectal cancer; however, the underlying molecular mechanism remains unclear. In this study, we sought to determine the role of Gas1 in tumorigenesis and metastasis, and elucidate the possible mechanism. First, Gas1 was determined as a negative regulator of oncogenesis and metastasis in colorectal cancer. Mechanistically, Gas1 negatively regulated the aerobic glycolysis, a process that contributed to tumor progression and metastasis by providing energy source and building blocks for macromolecule synthesis. To further consolidate the role of Gas1 in glycolysis, the impact of Gas1 in the transcription of key glycolytic enzymes for glucose utilization was examined. As expected, GLUT4, HK2, and LDHB exhibited a decreased expression pattern. Consistent with this observation, an in vivo subcutaneous xenograft mouse model also confirmed the hypothesis that Gas1 is a negative regulator of glycolysis as reflected by the decreased 18FDG uptake in PET/CT system. Moreover, Gas1 negatively regulated the AMPK/mTOR/p70S6K signaling axis, a well-established cascade that regulates malignant cancer cell behaviors including proliferation, metastasis, and aberrant cancer metabolism. In the end, it was determined that Gas1 is a transcriptional target of FOXM1, whose role in colorectal cancer has been widely studied. Taken together, these studies establish Gas1 as a negative regulator in colorectal cancer. IMPLICATIONS: Gas1 suppresses cell proliferation, invasion, and aerobic glycolysis of colorectal cancer both in vitro and in vivo Mechanistically, Gas1 inhibited EMT and the Warburg effect via AMPK/mTOR/p70S6K signaling, and Gas1 itself was directly regulated by the transcription factor FOXM1. Mol Cancer Res; 14(9); 830-40. (c)2016 AACR. PMID- 27401612 TI - Novel Bispecific Domain Antibody to LRP6 Inhibits Wnt and R-spondin Ligand Induced Wnt Signaling and Tumor Growth. AB - Aberrant WNT signaling is associated with the formation and growth of numerous human cancer types. The low-density lipoprotein receptor-related protein 6 (LRP6) is the least redundant component of the WNT receptor complex with two independent WNT ligand-binding sites. Using domain antibody (dAb) technology, a bispecific antibody (GSK3178022) to LRP6 was identified that is capable of blocking stimulation in the presence of a range of WNT and R-spondin (RSPO) ligands in vitro GSK3178022 was also efficacious in reducing WNT target gene expression in vivo, in both cancer cell line and patient-derived xenograft models, and delays tumor growth in a patient-derived RSPO fusion model of colorectal cancer. IMPLICATIONS: This article demonstrates the inhibition of a key oncogenic receptor, intractable to mAb inhibition due to multiple independent ligand interaction sites, using an innovative dAb approach. Mol Cancer Res; 14(9); 859 68. (c)2016 AACR. PMID- 27401613 TI - Transforming Big Data into Cancer-Relevant Insight: An Initial, Multi-Tier Approach to Assess Reproducibility and Relevance. AB - The Cancer Target Discovery and Development (CTD(2)) Network was established to accelerate the transformation of "Big Data" into novel pharmacologic targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding. This article represents a first attempt to delineate the challenges of supporting and confirming discoveries arising from the systematic analysis of large-scale data resources in a collaborative work environment and to provide a framework that would begin a community discussion to resolve these challenges. The Network implemented a multi-tier framework designed to substantiate the biological and biomedical relevance as well as the reproducibility of data and insights resulting from its collaborative activities. The same approach can be used by the broad scientific community to drive development of novel therapeutic and biomarker strategies for cancer. Mol Cancer Res; 14(8); 675-82. (c)2016 AACR. PMID- 27401614 TI - Prognostic role of liver X receptor-alpha in resected stage II and III non-small cell lung cancer. AB - INTRODUCTION: In the search of new therapeutical strategies against non-small cell lung cancer (NSCLC), the identification of new prognostic factors is crucial. OBJECTIVES: In this study, we analyzed the prognostic value of the liver X receptor-alpha (LXR-alpha), a nuclear receptor of a family of cholesterol derivatives called oxysterols, in patients with radically resected NSCLC. METHODS: We retrospectively reviewed 140 stage II and III surgically treated NSCLC patients that were grouped by percentage of LXR-alpha-positive cells value above or below its median value. Tumor-related survival was evaluated as primary end point. RESULTS: The 5-year overall and tumor-related survival rates were 40% and 46%, respectively. The median percentage of LXR-alpha-positive cells was 20%. Patients with stage II NSCLC had higher LXR-alpha values than those with stage III (P = .04). Univariate analysis demonstrated that both TNM stage and LXR-alpha were significantly related to tumor-related survival (P = .006 and P = .004, respectively). The 5-year tumor-related survival rates in stage II and III NSCLC were 56% and 34%, respectively. The 5-year tumor-related survival rates in high and low LXR-alpha value were 57% and 32%, respectively. The multivariate analysis showed that both TNM stage and LXR-alpha were independent prognostic factors (P = .01 and P = .007, respectively) with hazard ratio of 1.92 and 0.49, respectively. CONCLUSION: LXR-alpha seems to be an independent prognostic factor indicating a better survival in completely resected stage II and III NSCLC patients. PMID- 27401617 TI - Linkage and Genetic Association in Severe Asthma. AB - A significant body of work in the genetics of asthma currently exists. However, current knowledge has not been clarifying in understanding the pathophysiology of asthma and therapeutic treatment of the disease. Severe asthma in adults and children is a significant burden in relation to disproportionate disease morbidity, mortality, and health utilization. This disease phenotype is not well understood; current effective treatment regimens are limited. Genetic studies may lead to improved understanding of the pathophysiology of severe asthma and identification of relevant subsets, which allow more targeted and effective therapies and the realization of Precision Medicine in asthma. PMID- 27401615 TI - Effects of cathepsin K on Emdogain-induced hard tissue formation by human periodontal ligament stem cells. AB - Recent studies have shown that patients with pycnodysostosis caused by cathepsin K (CTSK) genetic mutations exhibit significantly abnormal periodontal hard tissue structure. This finding suggests that CTSK may play a role in regulating the development of alveolar bone and cementum. However, the source of CTSK in the periodontal environment and the role of CTSK in periodontal regeneration, particularly hard tissue regeneration and development, remain unclear. After the isolation, cultivation, identification, and multi-lineage induction of human periodontal ligament stem cells (hPDLSCs), the present study used light and scanning electron microscopy, reverse-transcription quantitative polymerase chain reaction, western blotting, micro-computed tomography, immunohistochemical assays and ectopic hard tissue formation experiments to examine CTSK expression in hPDLSCs. The results indicated that CTSK expression was significantly upregulated in hPDLSCs during Emdogain induction but underwent minimal change during osteogenic or adipogenic induction. The present study also showed that the downregulation of CTSK expression inhibited osteogenic/cementogenic differentiation and ectopic hard tissue formation of hPDLSCs. It is therefore concluded that hPDLSCs expressed CTSK and that CTSK levels were significantly upregulated during Emdogain induction. Furthermore, CTSK promoted not only the osteogenic/cementogenic differentiation of hPDLSCs but also their ability to form ectopic hard tissue. These new findings may enhance the understanding of periodontal hard tissue development and functional regeneration. However, the specific underlying mechanisms require further investigation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401616 TI - Epidemiology and Pulmonary Physiology of Severe Asthma. AB - The epidemiology and physiology of severe asthma are inherently linked because of varying phenotypes and expressions of asthma throughout the population. To understand how to better treat severe asthma, we must use both population data and physiologic principles to individualize therapies among groups with similar expressions of this disease. PMID- 27401618 TI - Psychosocial Factors in Severe Pediatric Asthma. AB - Asthma is the most common chronic illness among children in the United States and can impact nearly all aspects of functioning. Most research suggests that children with severe asthma display more emotional and behavioral problems than their healthy peers. These psychological difficulties are associated with increased risk for functional impairments and problematic disease course. Multidisciplinary teams that assess and treat these psychosocial factors using psychoeducational and behavioral interventions are important for children whose asthma is poorly controlled. Future research should examine the ways in which stress, emotions, and immune functions interact, so as to develop more preventative interventions. PMID- 27401619 TI - Role of Sleep Apnea and Gastroesophageal Reflux in Severe Asthma. AB - Gastroesophageal reflux and obstructive sleep apnea syndrome are conditions that practitioners have been encouraged to evaluate and treat as part of a comprehensive approach to achieving asthma control. In this review, the author looks at the evidence linking these two conditions as factors that may impact difficult-to-control asthma and looks critically at the evidence suggesting that evaluation and treatment of these conditions when present impacts asthma control. PMID- 27401620 TI - Role of Small Airways in Asthma. AB - Asthma is an inflammatory condition of both the small and large airways. Recently the small airways have gained attention as studies have shown significant inflammation in the small airways in all severities of asthma. This inflammation has correlated with peripheral airway resistance and as a result, noninvasive methods to reliably measure small airways have been pursued. In addition, recent changes in asthma inhalers have led to alterations in drug formulations and the development of extrafine particle inhalers that improve delivery to the distal airways. PMID- 27401621 TI - Chronic Infection and Severe Asthma. AB - Chronic bacterial infection is implicated in both the development and severity of asthma. The atypical bacteria Mycoplasma pneumoniae and Chlamydophila pneumoniae have been identified in the airways of asthmatics and correlated with clinical features such as adult onset, exacerbation risks, steroid sensitivity, and symptom control. Asthmatic patients with evidence of bacterial infection may benefit from antibiotic treatment directed towards these atypical organisms. Examination of the airway microbiome may identify microbial communities that confer risk for or protection from severe asthma. PMID- 27401622 TI - Chronic Rhinosinusitis and Aspirin-Exacerbated Respiratory Disease. AB - Patients with severe asthma and concomitant chronic rhinosinusitis often have severe, refractory upper and lower airway inflammation. This inflammation has been proposed to be similar throughout the upper and lower airways leading to the unified airways concept. This article reviews chronic rhinosinusitis with and without nasal polyps, and the subgroup with aspirin-exacerbated respiratory disease, while focusing on the relationship with asthma. Additionally, diagnosis and treatment with current and newer therapies are discussed. PMID- 27401623 TI - Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: Nothing New Under the Sun. AB - The debate about whether asthma and chronic obstructive pulmonary disease (COPD) are distinct clinical syndromes is not new; there is heightened interest in understanding the group of individuals with obstructive lung disease who seem to have elements of both conditions because recent studies have demonstrated increased risk for respiratory events and exacerbations. We describe the clinical characteristics of this subtype of disease and suggest 4 working definitions of individuals who would fall into the asthma-COPD overlap category. Understanding the mechanisms underlying these subtypes will hopefully lead into a better understanding of therapeutic strategies that can target specific pathobiologic pathways. PMID- 27401624 TI - Imaging of Asthma. AB - Asthma is one of the most common diseases of the lung. Asthma manifests with common, although often subjective and nonspecific, imaging features at radiography and high-resolution computed tomography. The primary role of imaging is not to make a diagnosis of asthma but to identify complications, such as allergic bronchopulmonary aspergillosis, or mimics of asthma, such as hypersensitivity pneumonitis. This article reviews the imaging features of asthma as well as common complications and mimics. PMID- 27401626 TI - Eosinophilic Endotype of Asthma. AB - Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. PMID- 27401627 TI - Neutrophilic and Pauci-immune Phenotypes in Severe Asthma. AB - Although 2 T-helper type 2 inflammation evokes airway hyperresponsiveness and narrowing, neutrophilic or pauci-immune asthma accounts for significant asthma morbidity. Viruses, toxicants, environmental tobacco smoke exposure, and bacterial infections induce asthma exacerbations mediated by neutrophilic inflammation or by structural cell (pauci-immune) mechanisms. Therapeutic challenges exist in the management of neutrophilic and pauci-immune phenotypes because both syndromes manifest steroid insensitivity. The recognition that neutrophil subsets exist and their functions are unique poses exciting opportunities to develop precise therapies. The conventional thought to target neutrophil activation or migration globally may explain why current drug development in neutrophilic asthma remains challenging. PMID- 27401625 TI - Biomarkers in Severe Asthma. AB - Biomarkers have been critical for studies of disease pathogenesis and the development of new therapies in severe asthma. In particular, biomarkers of type 2 inflammation have proven valuable for endotyping and targeting new biological agents. Because of these successes in understanding and marking type 2 inflammation, lack of knowledge regarding non-type 2 inflammatory mechanisms in asthma will soon be the major obstacle to the development of new treatments and management strategies in severe asthma. Biomarkers can play a role in these investigations as well by providing insight into the underlying biology in human studies of patients with severe asthma. PMID- 27401628 TI - Traditional Therapies for Severe Asthma. AB - Severe asthma is a complex and heterogeneous disease. The European Respiratory Society and American Thoracic Society guidelines define severe asthma for patients 6 years or older as "asthma which requires treatment with high-dose inhaled corticosteroids...plus a second controller or systemic corticosteroids to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy." This article reviews available traditional therapies, data behind their uses in severe asthma, and varying recommendations. As various asthma endotypes and phenotypes are better understood and characterized, targeted therapies should help improve disease outcomes, efficacy, and cost-effectiveness. PMID- 27401629 TI - Emerging Biologics in Severe Asthma. AB - Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by persistently elevated sputum and/or blood eosinophils and by a significant response to treatments that suppress eosinophilia. Eosinophil activity in the airway may be more important than their numbers and this needs to be investigated. Transcriplomic or Metabolomic signatures may also be useful to identify this endotype. PMID- 27401630 TI - Severe Asthma: Chipping Away at the Unmet Need. PMID- 27401631 TI - Severe Asthma: A Heterogeneous Disease. PMID- 27401632 TI - Population structure of a whale shark Rhincodon typus aggregation in the Red Sea. AB - The presence of whale sharks Rhincodon typus were recorded around Shib Habil, a small, coastal reef off the Red Sea coast of Saudi Arabia, from 2010 to 2015. A total of 267 suitable photographs resulting in the identification of 136 individuals, were documented from 305 encounters. Sharks were divided evenly between the sexes with no evidence of temporal or spatial segregation. All individuals were immature based on size estimates and, for males, juvenile clasper morphology. Scars were reported for 57% of R. typus with 15% showing evidence of propeller trauma. Estimates of population size and patterns of residency were calculated by modelling the lagged identification rate. Multiple models were run simultaneously and compared using the Akaike information criterion. An open population model was found to best represent the data and estimates a daily abundance between 15 and 34 R. typus during the aggregation season, with local residence times ranging from 4 to 44 days. Residence times away from Shib Habil range from 15 to 156 days with a permanent emigration-death rate between 0.07 and 0.58 individuals year(-1) . These results are broadly similar to those from other aggregations of R. typus, although the observed sexual parity and integration found at this site is unique for the species and needs further study. PMID- 27401633 TI - Robotic Radical Prostatectomy: What Do We Really Know about Its Outcomes? PMID- 27401634 TI - Intraductal Carcinoma of the Prostate Gland: Recent Advances. AB - Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up. PMID- 27401635 TI - Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer. AB - PURPOSE: To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. RESULTS: In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score >=2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score >=2 were found to be significant prognostic factors for patient survival. CONCLUSION: Dyspnea could be a significant prognostic factor in patients with NSCLC. PMID- 27401636 TI - Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. AB - PURPOSE: Docetaxel-based chemotherapy (DTX) improves overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC). Considering the potential existence of androgen receptors that remain active at this stage, we aimed to assess the impact of the combined use of androgen deprivation therapy (ADT) with DTX for mCRPC. MATERIALS AND METHODS: We performed a single institutional retrospective analysis of patients with mCRPC who received either DTX alone (DTX group, n=21) or concurrent DTX and ADT (DTX+ADT group, n=26) between August 2006 and February 2014. All patients received DTX doses of 75 mg/m2 every three weeks for at least three cycles. In the DTX+ADT group, all patients used luteinizing hormone releasing hormone agonist continuously as a concurrent ADT. RESULTS: The median follow-up period was 24.0 months (interquartile range 12.0-37.0) for the entire cohort. The median radiographic progression-free survival (rPFS) was 9.0 months and 6.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.036). On multivariable Cox regression analysis, concurrent administration of ADT was the only significant predictor of rPFS [hazard ratio (HR)=0.525, 95% confidence intervals (CI) 0.284-0.970, p=0.040]. The median OS was 42.0 and 38.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.796). On multivariable analysis, hemoglobin level at the time of DTX initiation was associated with OS (HR=0.532, 95% CI 0.381-0.744, p<0.001). CONCLUSION: In chemotherapy-naive patients with mCRPC, the combined use of ADT with DTX improved rPFS. Our result suggests that the concurrent administration of ADT and DTX is superior to DTX alone. PMID- 27401637 TI - Coronary Computed Tomographic Angiography Does Not Accurately Predict the Need of Coronary Revascularization in Patients with Stable Angina. AB - PURPOSE: To evaluate the ability of coronary computed tomographic angiography (CCTA) to predict the need of coronary revascularization in symptomatic patients with stable angina who were referred to a cardiac catheterization laboratory for coronary revascularization. MATERIALS AND METHODS: Pre-angiography CCTA findings were analyzed in 1846 consecutive symptomatic patients with stable angina, who were referred to a cardiac catheterization laboratory at six hospitals and were potential candidates for coronary revascularization between July 2011 and December 2013. The number of patients requiring revascularization was determined based on the severity of coronary stenosis as assessed by CCTA. This was compared to the actual number of revascularization procedures performed in the cardiac catheterization laboratory. RESULTS: Based on CCTA findings, coronary revascularization was indicated in 877 (48%) and not indicated in 969 (52%) patients. Of the 877 patients indicated for revascularization by CCTA, only 600 (68%) underwent the procedure, whereas 285 (29%) of the 969 patients not indicated for revascularization, as assessed by CCTA, underwent the procedure. When the coronary arteries were divided into 15 segments using the American Heart Association coronary tree model, the sensitivity, specificity, positive predictive value, and negative predictive value of CCTA for therapeutic decision making on a per-segment analysis were 42%, 96%, 40%, and 96%, respectively. CONCLUSION: CCTA-based assessment of coronary stenosis severity does not sufficiently differentiate between coronary segments requiring revascularization versus those not requiring revascularization. Conventional coronary angiography should be considered to determine the need of revascularization in symptomatic patients with stable angina. PMID- 27401638 TI - Early Effects of Intensive Lipid-Lowering Treatment on Plaque Characteristics Assessed by Virtual Histology Intravascular Ultrasound. AB - PURPOSE: The effects of short-term intensive lipid-lowering treatment on coronary plaque composition have not yet been sufficiently evaluated. We investigated the influence of short-term intensive lipid-lowering treatment on quantitative and qualitative changes in plaque components of non-culprit lesions in patients with acute coronary syndrome. MATERIALS AND METHODS: This was a prospective, randomized, open-label, single-center trial. Seventy patients who underwent both baseline and three-month follow-up virtual histology intravascular ultrasound were randomly assigned to either an intensive lipid-lowering treatment group (ezetimibe/simvastatin 10/40 mg, n=34) or a control statin treatment group (pravastatin 20 mg, n=36). Using virtual histology intravascular ultrasound, plaque was characterized as fibrous, fibro-fatty, dense calcium, or necrotic core. Changes in plaque components during the three-month lipid-lowering treatment were compared between the two groups. RESULTS: Compared with the control statin treatment group, there was a significant reduction in low-density lipoprotein cholesterol in the intensive lipid-lowering treatment group (-20.4+/ 17.1 mg/dL vs. -36.8+/-17.4 mg/dL, respectively; p<0.001). There were no statistically significant differences in baseline, three-month follow-up, or serial changes of gray-scale intravascular ultrasound parameters between the two groups. The absolute volume of fibro-fatty plaque was significantly reduced in the intensive lipid-lowering treatment group compared with the control group ( 1.5+/-3.4 mm3 vs. 0.8+/-4.7 mm3, respectively; p=0.024). A linear correlation was found between changes in low-density lipoprotein cholesterol levels and changes in the absolute volumes of fibro-fatty plaque (p<0.001, R2=0.209). CONCLUSION: Modification of coronary plaque may be attainable after only three months of intensive lipid-lowering treatment. PMID- 27401639 TI - Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model. AB - PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-alpha n=5] using a CricketTM Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-alpha groups, compared to the oil or saline group (82.1+/-5.1% and 94.6+/-2.2% compared to 49.6+/-14.0% and 46.5+/-9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-alpha group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis. PMID- 27401640 TI - Long-Term Outcome and Surveillance Colonoscopy after Successful Endoscopic Treatment of Large Sessile Colorectal Polyps. AB - PURPOSE: Although there is a consensus about the need for surveillance colonoscopy after endoscopic resection, the interval remains controversial for large sessile colorectal polyps. The aim of this study was to evaluate the long term outcome and the adequate surveillance colonoscopy interval required for sessile and flat colorectal polyps larger than 20 mm. MATERIALS AND METHODS: A total of 204 patients with large sessile and flat polyps who received endoscopic treatment from May 2005 to November 2011 in a tertiary referral center were included. RESULTS: The mean age was 65.1 years and 62.7% of the patients were male. The mean follow-up duration was 44.2 months and the median tumor size was 25 mm. One hundred and ten patients (53.9%) received a short interval surveillance colonoscopy (median interval of 6.3 months with range of 1-11 months) and 94 patients (46.1%) received a long interval surveillance colonoscopy (median interval of 13.6 months with range of 12-66 months). There were 14 patients (6.9%) who had local recurrence at the surveillance colonoscopy. Using multivariate regression analysis, a polyp size greater than 40 mm was shown to be independent risk factor for local recurrence. However, piecemeal resection and surveillance colonoscopy interval did not significantly influence local recurrence. CONCLUSION: Endoscopic treatment of large sessile colorectal polyps shows a favorable long-term outcome. Further prospective study is mandatory to define an adequate interval of surveillance colonoscopy. PMID- 27401641 TI - Blood Neutrophil-to-Lymphocyte Ratio Predicts Tumor Recurrence in Patients with Hepatocellular Carcinoma within Milan Criteria after Hepatectomy. AB - PURPOSE: The systemic inflammation biomarker, Neutrophil-to-Lymphocyte Ratio (NLR), has been reported as one of the adverse prognostic factors for hepatocellular carcinoma (HCC) patient. The purpose of this study was to evaluate whether NLR could predict the risk of recurrence and death for the HCC patient, according to Milan criteria after hepatectomy. MATERIALS AND METHODS: Retrospective analysis was performed on a database of HCC patients who underwent hepatectomy between March 2001 and December 2011. The cutoff value of NLR was decided by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate regression analyses were performed to identify predictive factors of recurrence and death. RESULTS: A total of 213 patients were included in the present study. The median follow-up period was 48 months. One hundred and seven patients were experienced tumor recurrence; forty of them recurred within 12 months (early recurrence). NLR >=1.505, albumin <=3.75 g/dL, microvascular invasion and high grade of cirrhosis were found to be independent factors for adverse recurrence-free survival in multivariate regression analysis. And NLR >=1.945 was also found as a prognosis factor for early recurrence by univariate regression analysis. CONCLUSION: Elevated preoperative NLR can be easily obtained and reliable biomarker for assessing the tumor recurrence and early recurrence of Milan criteria HCC after the initial hepatectomy. PMID- 27401642 TI - Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer. AB - PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received >=2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth. PMID- 27401643 TI - Three-Dimensional Ground Glass Opacity Ratio in CT Images Can Predict Tumor Invasiveness of Stage IA Lung Cancer. AB - PURPOSE: We investigated the relationship between various parameters, including volumetric parameters, and tumor invasiveness according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with completely resected stage IA lung adenocarcinoma. The correlation between several parameters [one-dimensional ground glass opacity (1D GGO) ratio, two-dimensional (2D) GGO ratio, three dimensional (3D) GGO ratio, 1D solid size, 2D solid size, and 3D solid size] and tumor invasiveness according to IASLC/ATS/ERS classification was investigated using receiver operating characteristic (ROC) analysis. Adenocarcinoma in situ and minimally invasive adenocarcinoma were referred to as noninvasive adenocarcinoma. RESULTS: The areas under the curve (AUC) to predict invasive adenocarcinoma for the 1D, 2D, and 3D GGO ratios were 0.962, 0.967, and 0.971, respectively. The optimal cut-off values for the 1D, 2D, and 3D GGO ratios were 38%, 62%, and 74%, respectively. The AUC values for 1D, 2D, and 3D solid sizes to predict invasive adenocarcinoma were 0.933, 0.944, and 0.903, respectively. The optimal cut-off values for 1D, 2D, and 3D solid sizes were 1.2 cm, 1.5 cm2, and 0.7 cm3, respectively. The difference in the ROC curves for 3D GGO ratio and 3D solid size was significant (p=0.01). CONCLUSION: Computed tomography image related parameters based on GGO were well correlated with and predictive of invasiveness according to IASLC/ATS/ERS classification. 3D GGO ratio was more strongly correlated with pathologic invasiveness than 3D solid size. PMID- 27401644 TI - Serum Procalcitonin as a Useful Serologic Marker for Differential Diagnosis between Acute Gouty Attack and Bacterial Infection. AB - PURPOSE: Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. MATERIALS AND METHODS: Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. RESULTS: Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096+/-0.105 ng/mL vs. 4.94+/-13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798-0.917, p<0.001], 0.808 (95% CI, 0.738-0.878, p<0.001), and 0.638 (95% CI, 0.544-0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). CONCLUSION: Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections. PMID- 27401645 TI - Urinary Continence after Robot-Assisted Laparoscopic Radical Prostatectomy: The Impact of Intravesical Prostatic Protrusion. AB - PURPOSE: To assess the impact of intravesical prostatic protrusion (IPP) on the outcomes of robot-assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS: The medical records of 1094 men who underwent RALP from January 2007 to March 2013 were analyzed using our database to identify 641 additional men without IPP (non-IPP group). We excluded 259 patients who presented insufficient data and 14 patients who did not have an MRI image. We compared the following parameters: preoperative transrectal ultrasound, prostate specific antigen (PSA), clinicopathologic characteristics, intraoperative characteristics, postoperative oncologic characteristics, minor and major postoperative complications, and continence until postoperative 1 year. IPP grade was stratified by grade into three groups: Grade 1 (IPP<=5 mm), Grade 2 (5 mm10 mm). RESULTS: Of the 821 patients who underwent RALP, 557 (67.8%) experienced continence at postoperative 3 months, 681 (82.9%) at 6 months, and 757 (92.2%) at 12 months. According to IPP grade, there were significant differences in recovering full continence at postoperative 3 months, 6 months, and 12 months (p<0.001). On multivariate analysis, IPP was the most powerful predictor of postoperative continence in patients who underwent RALP (p<0.001). Using a generalized estimating equation model, IPP also was shown to be the most powerful independent variable for postoperative continence in patients who underwent RALP (p<0.001). CONCLUSION: Patients with low-grade IPP have significantly higher chances of recovering full continence. Therefore, the known IPP grade will be helpful during consultations with patients before RALP. PMID- 27401646 TI - Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study. AB - PURPOSE: We report our initial experience with transurethral injection of autologous adipose-derived regenerative cells (ADRCs) for the treatment of urinary incontinence after radical prostatectomy. MATERIALS AND METHODS: After providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up. RESULTS: Urine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H2O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up. CONCLUSION: This study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence. PMID- 27401647 TI - Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study. AB - PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels >=10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: beta=0.263, p<0.001; age: beta=0.122, p=0.010; ESA dose: beta= 0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients. PMID- 27401649 TI - Risk Factors for the Rupture of Bifurcation Intracranial Aneurysms Using CT Angiography. AB - PURPOSE: To investigate the clinical and morphological characteristics in relation to risk of bifurcation intracranial aneurysm rupture. MATERIALS AND METHODS: Data from 202 consecutive patients with 219 bifurcation aneurysms (129 ruptured and 90 unruptured) managed at the authors' facility between August 2011 and July 2014 were retrospectively reviewed. Based on their clinical records and CT angiographic findings, the ability of risk factors to predict aneurysm rupture was assessed using statistical methods. RESULTS: Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were negatively correlated with aneurysm rupture. Aneurysms located in the middle cerebral artery, daughter artery ratio, lateral angle ratio (LA ratio), and neck width were negatively correlated with rupture. Aneurysms located in the anterior communicating artery, irregularity, with daughter sac, depth, width, maximum size, aspect ratio (AR), depth-to-width ratio, and bottleneck factor were significantly and positively correlated with rupture. Binary logistic regression model revealed that irregular shape [odds ratio (OR) 6.598] and AR (OR 3.507) strongly increased the risk of bifurcation aneurysm rupture, while age (OR 0.434), cerebral atherosclerosis (OR 0.125), neck width (OR 0.771), and LA ratio (OR 0.267) were negatively correlated with rupture (p<0.05). Receiver operating characteristic analysis revealed the threshold values of AR and LA ratio to be 1.18 and 1.50, respectively. CONCLUSION: Age (>=60 yr), cerebral atherosclerosis, and aneurysms with a larger neck width and larger LA ratio are protective factors against bifurcation aneurysm rupture. An aneurysm with an irregular shape and an increased AR reflect the greater likelihood of a rupture. PMID- 27401648 TI - Comparison of Robot-Assisted Radical Prostatectomy and Open Radical Prostatectomy Outcomes: A Systematic Review and Meta-Analysis. AB - PURPOSE: To systematically update evidence on the clinical efficacy and safety of robot-assisted radical prostatectomy (RARP) versus retropubic radical prostatectomy (RRP) in patients with prostate cancer. MATERIALS AND METHODS: Electronic databases, including ovidMEDLINE, ovidEMBASE, the Cochrane Library, KoreaMed, KMbase, and others, were searched, collecting data from January 1980 to August 2013. The quality of selected systematic reviews was assessed using the revised assessment of multiple systematic reviews and the modified Cochrane Risk of Bias tool for non-randomized studies. RESULTS: A total of 61 studies were included, including 38 from two previous systematic reviews rated as best available evidence and 23 additional studies that were more recent. There were no randomized controlled trials. Regarding safety, the risk of complications was lower for RARP than for RRP. Among functional outcomes, the risk of urinary incontinence was lower and potency rate was significantly higher for RARP than for RRP. Regarding oncologic outcomes, positive margin rates were comparable between groups, and although biochemical recurrence (BCR) rates were lower for RARP than for RRP, recurrence-free survival was similar after long-term follow up. CONCLUSION: RARP might be favorable to RRP in regards to post-operative complications, peri-operative outcomes, and functional outcomes. Positive margin and BCR rates were comparable between the two procedures. As most of studies were of low quality, the results presented should be interpreted with caution, and further high quality studies controlling for selection, confounding, and selective reporting biases with longer-term follow-up are needed to determine the clinical efficacy and safety of RARP. PMID- 27401650 TI - Therapeutic Efficacy of Oral Enteral Nutrition in Pediatric Crohn's Disease: A Single Center Non-Comparative Retrospective Study. AB - PURPOSE: Exclusive enteral nutrition (EEN) therapy effectively induces clinical remission in Crohn's disease (CD). It remains unclear, however, whether partial enteral nutrition (PEN) can maintain remission. This study was performed to determine the abilities of oral EEN and oral PEN to induce and maintain clinical remission in pediatric patients with CD, respectively. MATERIALS AND METHODS: Pediatric patients with CD who received oral EEN at a single center in 2000-2014 were identified retrospectively. Remission rates of the EEN and PEN during the 2 years study period were determined. Risk factors for EEN and PEN failure were identified. RESULTS: Of the 66 patients who started EEN, 61 (92%) completed the course. Clinical remission was achieved in 88% (58/66) of the patients. All 58 patients with remission continued with PEN: 43 (74%) were treatment adherent. The cumulative remission rates at 1 and 2 years were 67% and 52%, respectively. Differing from EEN, limited therapeutic efficacy of PEN was shown in severe CD patients. Female gender associated significantly with non-adherence. CONCLUSION: Oral EEN and PEN effectively induced and maintained remission in a pediatric population. Non-adherence was a limiting factor in the success of therapy. PMID- 27401651 TI - Comparisons of Oncologic Outcomes between Triple-Negative Breast Cancer (TNBC) and Non-TNBC among Patients Treated with Breast-Conserving Therapy. AB - PURPOSE: The optimum local surgical strategy regarding breast-conserving therapy (BCT) for triple-negative breast cancer (TNBC) is controversial. To investigate whether BCT is appropriate for patients with TNBC, we evaluated the clinical outcomes of BCT in women with TNBC compared to those of women without TNBC, using a large, single-center cohort. MATERIALS AND METHODS: We performed a retrospective analysis of 1533 women (TNBC n=321; non-TNBC n=1212) who underwent BCT for primary breast cancer between 2000 and 2010. Clinicopathological characteristics, locoregional recurrence-free survival (LRFS), and overall survival (OS) were analyzed. RESULTS: Tumors from the TNBC group had a higher T stage (T2 37.4% vs. 21.0%, p<0.001), a lower N stage (N0 86.9% vs. 75.5%, p<0.001), and a higher histologic grade (Grade III 66.8% vs. 15.4%, p<0.001) than the non-TNBC group. There were no differences in 5-year LRFS rates between the TNBC and non-TNBC groups (98.7% vs. 97.8%, p=0.63). The non-TNBC group showed a slightly better 5-year OS than the TNBC group; however, the difference was not significant (96.2% vs. 97.3%, p=0.72). In multivariate analyses, TNBC was not associated with poor clinical outcomes in terms of LRFS and OS [hazard ratio (HR) for LRFS=0.37, 95% confidence interval (CI): 0.10-1.31; HR for OS=1.03, 95% CI: 0.31-3.39]. CONCLUSION: TNBC patients who underwent BCT showed non-inferior locoregional recurrence compared to non-TNBC patients with BCT. Thus, BCT is an acceptable surgical approach in patients with TNBC. PMID- 27401652 TI - A Comparison between Clinical Results of Selective Bundle and Double Bundle Anterior Cruciate Ligament Reconstruction. AB - PURPOSE: The purpose of this study was to compare the clinical outcomes of arthroscopic anatomical double bundle (DB) anterior cruciate ligament (ACL) reconstruction with either selective anteromedial (AM) or posterolateral (PL) bundle reconstruction while preserving a relatively healthy ACL bundle. MATERIALS AND METHODS: The authors evaluated 98 patients with a mean follow-up of 30.8+/ 4.0 months who had undergone DB or selective bundle ACL reconstructions. Of these, 34 cases underwent DB ACL reconstruction (group A), 34 underwent selective AM bundle reconstruction (group B), and 30 underwent selective PL bundle reconstructions (group C). These groups were compared with respect to Lysholm and International Knee Documentation Committee (IKDC) score, side-to-side differences of anterior laxity measured by KT-2000 arthrometer at 30 lbs, and stress radiography and Lachman and pivot shift test results. Pre- and post-operative data were objectively evaluated using a statistical approach. RESULTS: The preoperative anterior instability measured by manual stress radiography at 90 degrees of knee flexion in group A was significantly greater than that in groups B and C (all p<0.001). At last follow-up, mean side-to-side instrumented laxities measured by the KT-2000 and manual stress radiography were significantly improved from preoperative data in all groups (all p<0.001). There were no significant differences between the three groups in anterior instability measured by KT-2000 arthrometer, pivot shift, or functional scores. CONCLUSION: Selective bundle reconstruction in partial ACL tears offers comparable clinical results to DB reconstruction in complete ACL tears. PMID- 27401653 TI - The Efficacy of Low Molecular Weight Heparin for the Prevention of Venous Thromboembolism after Hip Fracture Surgery in Korean Patients. AB - PURPOSE: The aim of this study was to investigate the efficacy of low-molecular weight heparin (LMWH) for the prevention of venous thromboembolism in Korean patients who underwent hip fracture surgery (HFS). MATERIALS AND METHODS: Prospectively, a total 181 cases were classified into the LMWH user group (116 cases) and LMWH non-user group (65 cases). Each group was sub-classified according to fracture types as follows: 81 cases of intertrochanteric fracture (group A: 49, group B: 32) and 100 cases of neck fracture (group C: 67, group D: 33). We compared the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) according to LMWH use. RESULTS: Of the 181 cases, four DVTs were found in the LMWH user groups (1 in group A, and 3 in group C). One case of PE was found in LMWH non-user group D. The incidences of DVT and PE showed no statistically significant differences between the LMWH user and non-user groups (p=0.298 and 0.359, respectively). In subgroup analysis, no statistically significant differences were found between groups A and B and between groups C and D. CONCLUSION: The administration of LMWH was not effective in the prevention of venous thromboembolism and PE in the Korean patients who underwent HFS. PMID- 27401654 TI - Surgical Outcome Predictor in Degenerative Lumbar Spinal Disease Based on Health Related Quality of Life Using Euro-Quality 5 Dimensions Analysis. AB - PURPOSE: We aim to introduce the predictive value of a quantitatively described formula model in a multicenter prospective analysis using the EuroQol-5 dimensions (EQ-5D) health scale to anticipate postoperative improvement in patients with degenerative lumbar spine disease (DLSD). MATERIALS AND METHODS: Quality of life was evaluated in 376 patients from 17 tertiary hospitals before and after spinal decompression and fusion surgery. The five items of the EQ-5D, mobility (M), self-care (S), usual activities (A), pain/discomfort (P), and anxiety/depression (D), were checked as level 1, 2, or 3, with 3 being the worst. A minimal significant change in the calculated EQ-5D (cEQ-5D) was set as 0.05. Logistic regression analysis was performed to predict the highest successful outcome (cEQ-5D improvement after operation >0.05) with the given sets of 5 items of the EQ-5D. RESULTS: In the cEQ-5D analysis, among patients with a formula score of S+A+2*P+D<=8, 18/68 (27%) showed significant improvement in the cEQ-5D at 1 year postoperatively (p<0.05). However, in patients with a formula score of >=9, 265/308 (86%) demonstrated significant improvements in the cEQ-5D at 1 year postoperatively (p<0.05). CONCLUSION: We suggest that S+A+2*P+D>=9 in the EQ-5D can quantitatively describe the better surgical outcome predictors for DLSD. With a definite DLSD lesion confirmed by an imaging study, patients who meet the formula scores of 9 or over and have refractory symptoms to non-operative treatment could be better surgical candidates resulting in satisfactory surgical outcomes of over 86%, than those who scored 8 or lower. PMID- 27401655 TI - Knowledge of HPV and Surgery among Women Who Underwent Cervical Conization: A Korean Multi-Center Study. AB - PURPOSE: Human papillomavirus (HPV) infection is a well-known cause of cervical cancer, which, along with its precursors, can be diagnosed and treated with cervical conization (CC). This study aimed to assess HPV- and procedure-related knowledge among women who had undergone CC. MATERIALS AND METHODS: Between February and May 2014, consecutive women who had undergone CC at five different educational hospitals were recruited. All patients had undergone a loop electrosurgical excision procedure as the method of CC. A survey was conducted with a self-developed, 29-item questionnaire, measuring knowledge related to HPV and CC. We analyzed the responses of 160 patients who completed the questionnaire. RESULTS: Mean total knowledge scores (+/-standard deviation) for HPV and CC were 5.2+/-3.0 of a possible 13.0 and 8.3+/-4.2 of a possible 16.0, respectively. While 73% of the patients knew that HPV is the main cause of cervical cancer, only 44% knew that HPV is sexually transmitted. The purpose of CC was correctly identified by 71% of the patients. However, 35% failed to indicate the anatomical area resected at the time of CC in the schematic diagram. Women who were younger (p<0.001), had higher education level (p<0.001), and higher family income (p=0.008) had higher knowledge scores. In contrast, neither interval from CC to survey nor disease severity were associated with total knowledge score. CONCLUSION: The level of knowledge related to HPV and CC was unexpectedly low in women who had undergone CC. Intuitive educational resources may improve this knowledge, and further cohort studies are warranted. PMID- 27401656 TI - The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome. AB - PURPOSE: To assess the distribution of births and spontaneous abortions, first trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". MATERIALS AND METHODS: 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). RESULTS: There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (chi2=2.7; p=0.100) and LMWH treated pregnancies (chi2=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (chi2=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. CONCLUSION: The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended. PMID- 27401657 TI - Effect of Co-Implantation of a Capsular Tension Ring on Clinical Outcomes after Cataract Surgery with Monofocal Intraocular Lens Implantation. AB - PURPOSE: The objective was to evaluate the effect of co-implantation of a preloaded capsular tension ring (CTR) and aberration-free monofocal intraocular lens (IOL) on clinical outcomes and visual quality after cataract surgery. MATERIALS AND METHODS: Patients who underwent cataract surgery were randomized into two groups that were implanted with a CTR and IOL (group 1, 26 eyes) or an IOL only (group 2, 26 eyes). At 1 and 3 months after surgery, visual acuity, refractive errors, refractive prediction errors, ocular aberrations, and modulation transfer function (MTF) were analyzed. At 3 months postoperatively, anterior chamber depth (ACD) and contrast sensitivity were evaluated. RESULTS: Group 1 showed greater hyperopic shift, which caused the refractive prediction error at 3 months after surgery to be significantly different between the two groups (p=0.049). Differences in ACD between the preoperative and postoperative periods tended to be greater in group 1 than in group 2. At 3 months postoperatively, internal MTF values at 20, 25, and 30 cycles per degree were significantly better in group 1 than in group 2 (p=0.034, 0.017, and 0.017, respectively). Contrast sensitivity showed comparable results at almost all spatial frequencies between the groups. CONCLUSION: Regarding visual acuity and quality, both groups showed comparable results. Co-implantation of a CTR and aberration-free monofocal IOL was associated with hyperopic refractive outcomes. Surgeons should consider the position of the IOL when planning co-implantation of a CTR and IOL. PMID- 27401658 TI - Predictors of False-Negative Results from Percutaneous Transthoracic Fine-Needle Aspiration Biopsy: An Observational Study from a Retrospective Cohort. AB - PURPOSE: We investigated factors predictive of false-negative pulmonary lesions with nonspecific benign cytology results on percutaneous transthoracic fine needle aspiration biopsy (FNAB). MATERIALS AND METHODS: We included 222 pulmonary lesions that had a nonspecific benign result from percutaneous transthoracic FNAB between March 2005 and December 2012, and were confirmed by subsequent pathologic results or adequate clinical follow up over at least 2 years. Clinical, imaging, and biopsy procedure-related findings were compared between lesions with a final diagnosis of malignancy (false-negative) and lesions with a benign diagnosis (true-negative). Multivariate logistic regression analysis was performed to identify significant predictors of false-negatives. RESULTS: Of 222 lesions, 115 lesions were proved to be false-negatives, and 107 were true-negatives. Compared with the true-negatives, false-negative lesions showed significantly older age (p=0.037), higher maximum standardized uptake value (SUVmax) on positron emission tomography (p=0.001), larger lesion size (p=0.007), and lesion characteristics of a subsolid nodule (p=0.007). On multivariate logistic regression analysis, SUVmax, lesion size, and lesion characteristics were significant predictors of false-negative results. CONCLUSION: Among the clinical, radiologic, and procedure related factors analyzed, high SUVmax, large lesion size, and subsolid lesions were useful for predicting malignancy in pulmonary lesions with nonspecific benign cytology results on FNAB. PMID- 27401659 TI - Oxidative Stress-Activated NHE1 Is Involved in High Glucose-Induced Apoptosis in Renal Tubular Epithelial Cells. AB - PURPOSE: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes mellitus involving disturbances in electrolytes and the acid-base balance caused by a disorder of glucose metabolism. NHE1 is a Na+/H+ exchanger responsible for keeping intracellular pH (pHi) balance and cell growth. Our study aimed to investigate roles of NHE1 in high glucose (HG)-induced apoptosis in renal tubular epithelial cells. MATERIALS AND METHODS: Renal epithelial tubular cell line HK-2 was cultured in medium containing 5 mM or 30 mM glucose. Then, cell apoptosis, oxidative stress, NHE1 expression, and pHi were evaluated. NHE1 siRNA and inhibitor were used to evaluate its role in cell apoptosis. RESULTS: HG significantly increased cell apoptosis and the production of reactive oxygen species (ROS) and 8-OHdG (p<0.05). Meanwhile, we found that HG induced the expression of NHE1 and increased the pHi from 7.0 to 7.6 after 48 h of incubation. However, inhibiting NHE1 using its specific siRNA or antagonist DMA markedly reduced cell apoptosis stimulated by HG. In addition, suppressing cellular oxidative stress using antioxidants, such as glutathione and N-acetyl cysteine, significantly reduced the production of ROS, accompanied by a decrease in NHE1. We also found that activated cyclic GMP-Dependent Protein Kinase Type I (PKG) signaling promoted the production of ROS, which contributed to the regulation of NHE1 functions. CONCLUSION: Our study indicated that HG activates PKG signaling and elevates the production of ROS, which was responsible for the induction of NHE1 expression and dysfunction, as well as subsequent cell apoptosis, in renal tubular epithelial cells. PMID- 27401660 TI - Protocol-Based Resuscitation for Septic Shock: A Meta-Analysis of Randomized Trials and Observational Studies. AB - PURPOSE: Owing to the recommendations of the Surviving Sepsis Campaign guidelines, protocol-based resuscitation or goal-directed therapy (GDT) is broadly advocated for the treatment of septic shock. However, the most recently published trials showed no survival benefit from protocol-based resuscitation in septic shock patients. Hence, we aimed to assess the effect of GDT on clinical outcomes in such patients. MATERIALS AND METHODS: We performed a systematic review that included a meta-analysis. We used electronic search engines including PubMed, Embase, and the Cochrane database to find studies comparing protocol based GDT to common or standard care in patients with septic shock and severe sepsis. RESULTS: A total of 13269 septic shock patients in 24 studies were included [12 randomized controlled trials (RCTs) and 12 observational studies]. The overall mortality odds ratio (OR) [95% confidence interval (CI)] for GDT versus conventional care was 0.746 (0.631-0.883). In RCTs only, the mortality OR (95% CI) for GDT versus conventional care in the meta-analysis was 0.93 (0.75 1.16). The beneficial effect of GDT decreased as more recent studies were added in an alternative, cumulative meta-analysis. No significant publication bias was found. CONCLUSION: The result of this meta-analysis suggests that GDT reduces mortality in patients with severe sepsis or septic shock. However, our cumulative meta-analysis revealed that the reduction of mortality risk was diminished as more recent studies were added. PMID- 27401661 TI - Prevalence and Antibiotic Susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in Pregnant Women. AB - Mycoplasma hominis (M. hominis) and Ureaplasma urealyticum (U. urealyticum) are important opportunistic pathogens that cause urogenital infections and complicate pregnancy. The aim of this study was to investigate the prevalence, effects on pregnancy outcomes, and antimicrobial susceptibilities of M. hominis and U. urealyticum. We tested vaginal swabs obtained from 1035 pregnant women for the presence of genital mycoplasmas between June 2009 and May 2014. The laboratory and clinical aspects of genital mycoplasmas infection were reviewed retrospectively, and the identification and antimicrobial susceptibility of genital mycoplasmas were determined using the Mycoplasma IST-2 kit. A total of 571 instances of M. hominis and/or U. urealyticum were detected. Of them, M. hominis was detected in two specimens, whereas U. urealyticum was detected in 472 specimens. The remaining 97 specimens were positive for both M. hominis and U. urealyticum. Preterm deliveries were frequently observed in cases of mixed infection of M. hominis and U. urealyticum, and instances of preterm premature rupture of membrane were often found in cases of U. urealyticum. The rates of non susceptible isolates to erythromycin, empirical agents for pregnant women, showed increasing trends. In conclusion, the prevalence of M. hominis and/or U. urealyticum infections in pregnant women is high, and the resistance rate of antimicrobial agents tends to increase. Therefore, to maintain a safe pregnancy, it is important to identify the isolates and use appropriate empirical antibiotics immediately. PMID- 27401663 TI - Platelet-Rich Fibrin Lysate Can Ameliorate Dysfunction of Chronically UVA Irradiated Human Dermal Fibroblasts. AB - To determine whether platelet-rich fibrin lysate (PRF-L) could restore the function of chronically ultraviolet-A (UVA)-irradiated human dermal fibroblasts (HDFs), we isolated and sub-cultured HDFs from six different human foreskins. HDFs were divided into two groups: those that received chronic UVA irradiation (total dosages of 10 J cm-2) and those that were not irradiated. We compared the proliferation rates, collagen deposition, and migration rates between the groups and between chronically UVA-irradiated HDFs in control and PRF-L-treated media. Our experiment showed that chronic UVA irradiation significantly decreased (p<0.05) the proliferation rates, migration rates, and collagen deposition of HDFs, compared to controls. Compared to control media, chronically UVA-irradiated HDFs in 50% PRF-L had significantly increased proliferation rates, migration rates, and collagen deposition (p<0.05), and the migration rates and collagen deposition of chronically UVA-irradiated HDFs in 50% PRF-L were equal to those of normal fibroblasts. Based on this experiment, we concluded that PRF-L is a good candidate material for treating UVA-induced photoaging of skin, although the best method for its clinical application remains to be determined. PMID- 27401664 TI - Bone Marrow Suppression and Hemophagocytic Histiocytes Are Common Findings in Korean Severe Fever with Thrombocytopenia Syndrome Patients. AB - The causes of cytopenia in patients with severe fever with thrombocytopenia syndrome (SFTS) are not fully understood until now. We reviewed the bone marrow (BM) findings of patients with SFTS to unravel the cause of the cytopenia. Three Korean SFTS were enrolled in this study. Thrombocytopenia, neutropenia, and anemia were detected in all three patients. Severe hypocellular marrow (overall cellularity <5%) and a decreased number of megakaryocytes were noted in one patient, and hypo-/normocellular marrow and an increased number of hemophagocytic histiocytes were observed in two patients. Megakaryocytes were relatively preserved in two patients. Although a limited number of cases are available, our observations suggest that both BM suppression and peripheral destruction or sequestration are causes of cytopenia of patients with SFTS. To the best of our knowledge, this is the first well documented pathologic evaluation of Korean SFTS. PMID- 27401662 TI - Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy. AB - Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5 FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID- 27401665 TI - Three Cases of Spondyloepiphyseal Dysplasia Tarda in One Korean Family. AB - Spondyloepiphyseal dysplasia (SED) tarda is an inherited skeletal arthropathy. Because SED tarda involves the joints and resemble the clinical findings of chronic arthropathies, this disease is frequently misdiagnosed as juvenile idiopathic arthritis (JIA). We report here on three patients (father and his two daughters) in one family with SED tarda. All patients had back pain and polyarthralgia. Their radiographs revealed typical changes for SED tarda including platyspondyly and dysplastic bone changes. This rare disease has major clinical importance in that it is similar with JIA or rheumatoid arthritis. PMID- 27401666 TI - When Eastern Surgeons Meet Western Patients: A Pilot Study of Gastrectomy with Lymphadenectomy in Caucasian Patients at a Single Korean Institute. AB - East Asian surgeons generally report lower morbidity and mortality rates for gastrectomy with D2 lymphadenectomy than do surgeons in Western countries; however, the disparity remains unexplained. The aim of this article was to determine the feasibility and safety regarding cases in which East Asian surgeons perform such procedures in Caucasian patients (CPs). Twelve CPs underwent gastrectomy with lymphadenectomy for gastric cancer at Yonsei University Severance Hospital, Seoul, Korea between June 2011 and April 2014. Procedures performed included total gastrectomy (7 of 12, 58%), distal gastrectomy (4 of 12, 33%), and completion total gastrectomy (1 of 12, 8%). Nine patients (75%) underwent D2 lymphadenectomy, and D1+ lymphadenectomy was performed in three others (25%). In four patients (33%), combined resections were carried out. The median values of surgical parameters were as follows: operative time, 266.5 min (range, 120-586 min); estimated blood loss, 90 mL (range, 37-350 mL); retrieved lymph node count, 37.5 (range, 22-63); and postoperative hospital stay, 13.7 days (range, 5-63 days). No mortality was encountered, although two patients (17%) experienced complications (both Clavien-Dindo classification grade IIIa anastomotic leakages), which were successfully managed by conservative treatment. In the hands of East Asian surgeons, mortality and short-term morbidity appears to be acceptably low in CPs subjected to gastrectomy with lymphadenectomy for gastric cancer. PMID- 27401667 TI - Using the Young Mania Rating Scale for Identifying Manic Symptoms in Patients with Schizophrenia. PMID- 27401668 TI - THE QUEST TO DESIGN BETTER EXPERIMENTS. AB - First suggested by R.A. Fisher in the 1930s, design of experiments (DOE) strategies are finding their way into modern life science research. Jeffrey Perkel looks at how DOE is impacting everything from genome editing to mass spectrometry. PMID- 27401669 TI - [Letter to the Editor] The need for improved education and training in research antibody usage and validation practices. AB - Address correspondence to Leonard P. Freedman, Global Biological Standards Institute, 1020 19th Street, NW, Suite 550, Washington, DC, 20036. E-mail: lfreedman@gbsi.org. PMID- 27401670 TI - Comparison of fluorescent intercalating dyes for quantitative loop-mediated isothermal amplification (qLAMP). AB - Real-time or quantitative loop-mediated isothermal amplification (qLAMP) is a promising technique for the accurate detection of pathogens in organisms and the environment. Here we present a comparative study of the performance of six fluorescent intercalating dyes-SYTO-9, SYTO-13, SYTO-82, SYBR Green I, SYBR Gold, EvaGreen-in three different qLAMP model systems. SYTO-9 and SYTO-82, which had the best results, were used for additional enzyme and template titration studies. SYTO-82 demonstrated the best combination of time-to-threshold (Tt) and signal-to noise ratio (SNR). PMID- 27401671 TI - Digital gene expression analysis with sample multiplexing and PCR duplicate detection: A straightforward protocol. AB - Tag-Seq is a high-throughput approach used for discovering SNPs and characterizing gene expression. In comparison to RNA-Seq, Tag-Seq eases data processing and allows detection of rare mRNA species using only one tag per transcript molecule. However, reduced library complexity raises the issue of PCR duplicates, which distort gene expression levels. Here we present a novel Tag-Seq protocol that uses the least biased methods for RNA library preparation combined with a novel approach for joint PCR template and sample labeling. In our protocol, input RNA is fragmented by hydrolysis, and poly(A)-bearing RNAs are selected and directly ligated to mixed DNA-RNA P5 adapters. The P5 adapters contain i5 barcodes composed of sample-specific (moderately) degenerate base regions (mDBRs), which later allow detection of PCR duplicates. The P7 adapter is attached via reverse transcription with individual i7 barcodes added during the amplification step. The resulting libraries can be sequenced on an Illumina sequencer. After sample demultiplexing and PCR duplicate removal with a free software tool we designed, the data are ready for downstream analysis. Our protocol was tested on RNA samples from predator-induced and control Daphnia microcrustaceans. PMID- 27401673 TI - Development of a bench-top extra-cleanroom for DNA amplification. AB - Prevention of airborne contamination has become an important factor in biotechnology; however, conventional laminar-airflow cabinets (LAF-cabinets) are no longer sufficient as a countermeasure against nano-sized airborne contaminants in the laboratory. Here we present a bench-top extra-cleanroom classified as ISO 1 that can prevent contamination from airborne nanoparticles. This bench-top extra-cleanroom consists of a novel clean-zone-creating system that is equipped with nanofibrous, nonwoven filters. In addition, the cleanroom is also equipped with an ionizer to prevent plasticware from collecting dust by electrostatic charge attraction. This combination of features allows the cleanroom to prevent DNA contamination derived from airborne nanoparticles. Our extra-cleanroom with ionizer could be useful in various areas of biotechnology that are easily affected by airborne contaminants. PMID- 27401674 TI - Relationship between transfusion volume and outcomes in children undergoing noncardiac surgery. AB - BACKGROUND: The objective of this study was to assess the relationship between the volume of red blood cells (RBCs) transfused and outcomes in children undergoing noncardiac surgery. STUDY DESIGN AND METHODS: Children undergoing noncardiac surgery recorded in the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) pediatric databases were included. Outcomes included 30-day mortality and the incidence of major postoperative complications. Children who received RBC transfusions were further classified into four subgroups based on the volume transfused. We used multivariable logistic regression analysis and propensity-matched analysis to match each child who received a transfusion with a nontransfused control and to compare the incidences of 30-day mortality and adverse postoperative outcomes. RESULTS: After propensity-matched analysis, there were 4496 children in the group that received transfusion volumes from 1 to 19 mL/kg, 1557 in the group that received volumes from 20 to 39 mL/kg, 506 in the group that received from 40 to 59 mL/kg, and 412 in the group that received >=60 mL/kg. Children who received RBC transfusion volumes from 40 to 59 mL/kg and >=60 mL/kg had an increased risk for 30-day mortality of 7.3% versus 1.4% (p < 0.001) and 11.2% versus 2.9% (p = 0.005), respectively, compared with their matched controls. No statistical difference was reported for children who were exposed to transfusion volumes from 20 to 39 mL/kg (3.3% vs 1.3%; p = 0.021), or from 1 to 19 mL/kg (1.4% vs. 1.2%; p = 0.691). Although no effect was observed on the incidence of postoperative renal failure or wound complications, RBC transfusions were associated with an increased incidence of postoperative infection when the volume transfused exceeded 20 mL/kg. CONCLUSIONS: RBC transfusion is associated with an increased incidence of 30-day mortality and postoperative infections in children undergoing noncardiac surgery, and there is a correlation between the volume of red blood cells transfused and the incidences of adverse outcomes. Potential associations related to the reason to transfuse, the cause of the bleeding, or the actual blood products themselves need to be studied in further prospective trials. PMID- 27401672 TI - A phased strategy to differentiate human CD14+monocytes into classically and alternatively activated macrophages and dendritic cells. AB - There are currently several in vitro strategies to differentiate human CD14(+) monocytes isolated from peripheral blood mononuclear cells (PBMCs) into the M1 or M2 macrophage cell types. Each cell type is then verified using flow cytometric analysis of cell-surface markers. Human CD14(+) monocytes have the potential to differentiate into M1 and M2 macrophages, both of which demonstrate varying degrees of cell-surface antigen overlap. Using multiple surface markers with current macrophage polarization protocols, our data reveal several limitations of currently used methods, such as highly ambiguous cell types that possess cell surface marker overlap and functional similarities. Utilizing interleukin-6 (IL 6) and two phases of cytokine exposure, we have developed a protocol to differentiate human monocytes into M1, M2, or dendritic cells (DCs) with greater efficiency and fidelity relative to macrophages and DCs that are produced by commonly used methods. This is achieved via alterations in cytokine composition, dosing, and incubation times, as well as improvements in verification methodology. Our method reliably reproduces human in vitro monocyte-derived DCs and macrophage models that will aid in better defining and understanding innate and adaptive immunity, as well as pathologic states. PMID- 27401675 TI - Role of epistasis on the fixation probability of a non-mutator in an adapted asexual population. AB - The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process. Using a multitype branching process, the fixation probability of a single non-mutator emerging in a large asexual mutator population is analytically calculated here. The mutator population undergoes deleterious mutations at constant, but at a much higher rate than that of the non-mutator. We find that antagonistic epistasis lowers the chances of mutation rate reduction, while synergistic epistasis enhances it. Below a critical value of epistasis, the fixation probability behaves non-monotonically with variation in the mutation rate of the background population. Moreover, the variation of this critical value of the epistasis parameter with the strength of the mutator is discussed in the appendix. For synergistic epistasis, when selection is varied, the fixation probability reduces overall, with damped oscillations. PMID- 27401676 TI - Developmental trajectories of EEG sleep slow wave activity as a marker for motor skill development during adolescence: a pilot study. AB - Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG-derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high-density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait-like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence. PMID- 27401677 TI - Parental knowledge, attitudes and beliefs regarding fever in children: an interview study. AB - BACKGROUND: Fever is one of the most common childhood symptoms. It causes significant worry and concern for parents. Every year there are numerous cases of over- and under-dosing with antipyretics. Caregivers seek reassurance from a variety of sources including healthcare practitioners. The aim of this study was to describe parental knowledge, attitudes and beliefs regarding management of childhood fever in children aged 5 years and under. METHOD: Semi-structured interviews were conducted with 23 parents at six ante-natal clinics in the south west of Ireland during March and April 2015. The Francis method was used to detect data saturation and thereby identify sample size. Thematic analysis was used to analyse the data. RESULTS: Twenty-three parents participated in the study. Five themes emerged from the data: assessing and managing the fever; parental knowledge and beliefs regarding fever; knowledge source; pharmaceutical products; initiatives. Parents illustrated a good knowledge of fever as a symptom. However, management practices varied between participants. Parents revealed a reluctance to use medication in the form of suppositories. There was a desire for more accessible, consistent information to be made available for use by parents when their child had a fever or febrile illness. CONCLUSION: Parents indicated that further initiatives are required to provide trustworthy information on the management of fever and febrile illness in children. Healthcare professionals should play a significant role in educating parents in how to manage fever and febrile illnesses in their children. The accessible nature and location of pharmacies could provide useful support for both parents and General Practitioners. PMID- 27401678 TI - "A place at the table:" a qualitative analysis of community board members' experiences with academic HIV/AIDS research. AB - BACKGROUND: Community advisory boards (CAB) are proposed as one mechanism to carry out successful community based participatory research (CBPR), but the presence of CABs may be insufficient to optimize academic-community partnerships. METHODS: We conducted semi-structured interviews with minority members of a CAB partnered with a HIV/AIDS research center and identified three themes. RESULTS: First, lack of trust in researchers included two subthemes: researchers' lacked respect for community-based organizations' (CBO's) interests and paid inadequate attention to building trust. Second, power imbalance included three subthemes: CAB members felt like inferior "token" members, felt that a lack of communication led to disempowerment, and held preconceived beliefs of researchers that led to perceived power imbalance. Third, CAB members suggested best practices, including using collaborations to build trust, actively allocating power, and sharing tangible research benefits with CBOs. CONCLUSIONS: Our findings indicate that CABs must be founded on trust and instilled with power to meet the tenets of CBPR. PMID- 27401679 TI - MMP2, MMP9 and TIMP2 polymorphisms affect sperm parameters but not fertility in Polish males. AB - Proper function of the blood-testis barrier is pivotal to spermatogenesis. Synchronised action of matrix metalloproteinases (MMP) and their inhibitors (TIMP) is mandatory to maintain dynamic balance of the barrier. Therefore, the association of functional genetic variants of MMP-2, MMP-9 and TIMP-2 and male infertility was studied. A total of 416 infertile males and 421 healthy subjects were genotyped for 7 SNPs within MMP2, MMP9 and TIMP2 genes, along with the assessment of semen parameters (concentration, motility and morphology of spermatozoa). No association was observed between the studied genotypes and male infertility. However, higher sperm concentration was associated with TIMP2 rs8080623 C and rs2277698 T variants among infertile men, and with MMP9 rs17576 A minor allele in controls (p < .05). TIMP2 rs9900972 T and rs2277698 T allele were associated with higher percentage of morphologically normal spermatozoa among controls. MMP2 rs2285053 TT homozygous infertile patients presented higher percentage of spermatozoa displaying nonprogressive motility. Haplotype analysis revealed strong linkage disequilibrium between the studied loci (5 of 8 possible TIMP2 haplotypes, and 3 of 4 possible MMP2 and MMP9 were found). None of the haplotypes showed association with infertility. This study results suggest an association between MMP9 and TIMP2 SNPs with sperm parameters, but not infertility. PMID- 27401680 TI - Type of opioid dependence among patients seeking opioid substitution treatment: are there differences in background and severity of problems? AB - BACKGROUND: The study explores differences and similarities in background and problem severity among those seeking Opioid Substitution Treatment (OST), comparing those who primarily had misused "opiates", e.g. heroin, morphine and opium, with those who primarily had misused other opioids. METHODS: Patients (n = 127) assessed for possible admittance in OST are compared based on the Addiction Severity Index. Two groups based on primary type of opioid misused are compared (opiates vs. other opioids). RESULTS: In the global severity ratings there were no significant differences between the groups other than tautological artefacts concerning heroin. There were few specific differences between the groups. The opiate group more often had Hepatitis C and more often had legal problems related to financing their misuse. Injection of drugs was the main method of administration in both groups, i.e. 90 % for mostly opiates vs. 75 % for mostly other opioids. A great majority in both groups, 96 % vs. 91 %, had misused most other types of drugs. Both groups were found to have severe problems in all areas investigated. CONCLUSIONS: The study demonstrates great similarities in problem severity among those seeking OST, both those who primarily had misused opiates and those who primarily had misused other opioids. PMID- 27401681 TI - Decision Trajectories in Dementia Care Networks: Decisions and Related Key Events. AB - This prospective multiperspective study provides insight into the decision trajectories of people with dementia by studying the decisions made and related key events. This study includes three waves of interviews, conducted between July 2010 and July 2012, with 113 purposefully selected respondents (people with beginning to advanced stages of dementia and their informal and professional caregivers) completed in 12 months (285 interviews). Our multilayered qualitative analysis consists of content analysis, timeline methods, and constant comparison. Four decision themes emerged-managing daily life, arranging support, community living, and preparing for the future. Eight key events delineate the decision trajectories of people with dementia. Decisions and key events differ between people with dementia living alone and living with a caregiver. Our study clarifies that decisions relate not only to the disease but to living with the dementia. Individual differences in decision content and sequence may effect shared decision-making and advance care planning. PMID- 27401682 TI - Evaluation of the Antioxidant and Antiproliferative Effects of Three Peptide Fractions of Germinated Soybeans on Breast and Cervical Cancer Cell Lines. AB - Soybeans are an important source of bioactive molecules, such as peptides, which generation can improve through germination. In this study, the antioxidant and antiproliferative activities of three peptide fractions (>10 kDa, 5-10 kDa and <5 kDa) that were obtained by ultrafiltration of soybean protein hydrolysate after six days of germination were evaluated. The antioxidant activities of the peptide fractions were assessed by reducing power, Cu+2 and Fe+2 chelation and OH. scavenging assays, whereas their antiproliferative effects against cervical (HeLa, SiHa, CasKi) and breast (MCF7 and MDA-MB-231) cancer cell lines were evaluated by the MTT assay. Apoptosis was determined by Hoechst-PI staining. The most active peptide fraction (MAPF) was the >10 kDa fraction, which showed the greatest antioxidant and antiproliferative activity. The most sensitive cancer cell lines were the HeLa, CasKi and MDA-MB-231 cells, which had IC50 values of 16.2, 14.3 and 15.2 mg/mL, respectively, and apoptotic indices above 50 % after 6 or 8 h of exposure. The effect of MAPF on normal cells (HaCaT) was minimal. The amino acid composition of MAPF was characterized by high proline, phenylalanine and tyrosine content, and MALDI-TOF/TOF analysis showed six signals with molecular weights of 12 to 42 kDa. PMID- 27401683 TI - Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology. AB - Despite being one of the most common oral mucosal diseases and recognized as early as 1866, oral lichen planus (OLP) is still a disease without a clear etiology or pathogenesis, and with uncertain premalignant potential. More research is urgently needed; however, the research material must be based on an accurate diagnosis. Accurate identification of OLP is often challenging, mandating inclusion of clinico-pathological correlation in the diagnostic process. This article summarizes current knowledge regarding OLP, discusses the challenges of making an accurate diagnosis, and proposes a new set of diagnostic criteria upon which to base future research studies. A checklist is also recommended for clinicians to provide specific information to pathologists when submitting biopsy material. The diagnostic process of OLP requires continued clinical follow-up after initial biopsy, because OLP mimics can manifest, necessitating an additional biopsy for direct immunofluorescence study and/or histopathological evaluation in order to reach a final diagnosis. PMID- 27401684 TI - Tools and techniques for computational reproducibility. AB - When reporting research findings, scientists document the steps they followed so that others can verify and build upon the research. When those steps have been described in sufficient detail that others can retrace the steps and obtain similar results, the research is said to be reproducible. Computers play a vital role in many research disciplines and present both opportunities and challenges for reproducibility. Computers can be programmed to execute analysis tasks, and those programs can be repeated and shared with others. The deterministic nature of most computer programs means that the same analysis tasks, applied to the same data, will often produce the same outputs. However, in practice, computational findings often cannot be reproduced because of complexities in how software is packaged, installed, and executed-and because of limitations associated with how scientists document analysis steps. Many tools and techniques are available to help overcome these challenges; here we describe seven such strategies. With a broad scientific audience in mind, we describe the strengths and limitations of each approach, as well as the circumstances under which each might be applied. No single strategy is sufficient for every scenario; thus we emphasize that it is often useful to combine approaches. PMID- 27401685 TI - Bipolar cells precede bipolar minds - But relations are complex. PMID- 27401686 TI - The Joubert Syndrome Protein Inpp5e Controls Ciliogenesis by Regulating Phosphoinositides at the Apical Membrane. AB - Phosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear. Here, we utilized an in vivo vertebrate model of renal cystogenesis to show that Inpp5e enzymatic activity at the apical membrane directs apical docking of basal bodies in renal epithelia. Knockdown or knockout of inpp5e led to ciliogenesis defects and cystic kidneys in zebrafish. Furthermore, knockdown of inpp5e in embryos led to defects in cell polarity, cortical organization of F-actin, and apical segregation of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 Knockdown of the ezrin gene, which encodes an ezrin/radixin/moesin (ERM) protein that crosslinks PtdIns(4,5)P2 and F-actin, phenocopied inpp5e knockdowns. Notably, overexpression of the ezrin gene rescued inpp5e morphants. Finally, treatment with the PI 3-kinase inhibitor LY294002, which decreases PtdIns(3,4,5)P3 levels, rescued the cellular, phenotypic, and renal functional defects in inpp5e-knockdown embryos. Together, our data indicate that Inpp5e functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns(3,4,5)P3 and subsequently stabilizing PtdIns(4,5)P2 and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies. PMID- 27401687 TI - High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKD. AB - High levels of proenkephalin-A (pro-ENK) have been associated with decreased eGFR in an acute setting. Here, we examined whether pro-ENK levels predict CKD and decline of renal function in a prospective cohort of 2568 participants without CKD (eGFR>60 ml/min per 1.73 m2) at baseline. During a mean follow-up of 16.6 years, 31.7% of participants developed CKD. Participants with baseline pro-ENK levels in the highest tertile had significantly greater yearly mean decline of eGFR (Ptrend<0.001) and rise of cystatin C (Ptrend=0.01) and creatinine (Ptrend<0.001) levels. Furthermore, compared with participants in the lowest tertile, participants in the highest tertile of baseline pro-ENK concentration had increased CKD incidence (odds ratio, 1.51; 95% confidence interval, 1.18 to 1.94) when adjusted for multiple factors. Adding pro-ENK to a model of conventional risk factors in net reclassification improvement analysis resulted in reclassification of 14.14% of participants. Genome-wide association analysis in 4150 participants of the same cohort revealed the strongest association of pro ENK levels with rs1012178 near the PENK gene, where the minor T-allele associated with a 0.057 pmol/L higher pro-ENK level per allele (P=4.67x10-21). Furthermore, the T-allele associated with a 19% increased risk of CKD per allele (P=0.03) and a significant decrease in the instrumental variable estimator for eGFR (P<0.01) in a Mendelian randomization analysis. In conclusion, circulating plasma pro-ENK level predicts incident CKD and may aid in identifying subjects in need of primary preventive regimens. Additionally, the Mendelian randomization analysis suggests a causal relationship between pro-ENK level and deterioration of kidney function over time. PMID- 27401688 TI - The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. AB - Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume*glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons. PMID- 27401690 TI - Nosocomial candidemia in patients admitted to medicine wards compared to other wards: a multicentre study. AB - PURPOSE: Risk factors for nosocomial candidemia, severity of sepsis, treatment, and outcome were compared between patients admitted to medicine wards and those to surgical and intensive care units (ICUs). METHODS: Data were retrospectively collected from patients belonging to six referral hospitals in Italy between January 2011 and December 2013. Risk factors for 30-day mortality were evaluated in the whole patient population. RESULTS: A total of 686 patients (mean age 70 +/ 15 years) with candidemia were included. 367 (53.5 %) patients were in medicine wards, and 319 in surgery and ICUs. Host-related risk factors for candidemia were more common in medicine patients whereas healthcare-related factors in surgery/ICU patients. These patients showed severe sepsis and septic shock more commonly (71.7 %) than medicine patients (59.9 %) (p 0.003). The latter underwent central venous catheter (CVC) removal and adequate antifungal therapy less frequently than surgery/ICU patients. 149 (40.6 %) patients died with candidemia in medicine wards and 69 (21.6 %) in other wards (p < 0.001). Overall, the 30-day mortality was 36.3 %. At multivariate analysis, independent risk factors for death were aging, higher Charlson score, severe sepsis and septic shock, and no antifungal therapy, while major surgery and CVC removal were associated with higher probability of survival. CONCLUSIONS: The burden of risk factors for candidemia was different between medicine patients and those in other wards. Despite the lower severity of candidemia in medicine patients, their mortality turned out to be higher than in surgery or ICU patients. Awareness of the best management of candidemia should be pursued, especially in medicine wards. PMID- 27401689 TI - Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health Initiative. AB - Pragmatic clinical trials are conducted under the real-world conditions of clinical care delivery. As a result, these trials yield findings that are highly generalizable to the nonresearch setting, identify interventions that are readily translatable into clinical practice, and cost less than trials that require extensive research infrastructures. Maintenance dialysis is a setting especially well suited for pragmatic trials because of inherently frequent and predictable patient encounters, highly granular and uniform data collection, use of electronic data systems, and delivery of care by a small number of provider organizations to approximately 90% of patients nationally. Recognizing the potential for pragmatic trials to generate much needed evidence to guide the care of patients receiving maintenance dialysis, the Kidney Health Initiative assembled a group of individuals with relevant expertise from academia, industry, and government to provide the nephrology community with information about the design and conduct of such trials, with a specific focus on the dialysis setting. Here, we review this information, and where applicable, use experience from the ongoing Time to Reduce Mortality in End Stage Renal Disease Trial, a large cluster-randomized, pragmatic trial evaluating hemodialysis session duration, to illustrate challenges and solutions to operational, ethical, and regulatory issues. PMID- 27401692 TI - Multi-gene panel testing for hereditary cancer susceptibility in a rural Familial Cancer Program. AB - This study explores our Familial Cancer Program's experience implementing multi gene panel testing in a largely rural patient population. We conducted a retrospective review of patients undergoing panel testing between May 2011 and August 2015. Our goal was to evaluate factors that might be predictors of identifying variants (pathogenic or uncertain significance) and to assess clinical management changes due to testing. We utilized a structured family history tool to determine the significance of patient's family histories with respect to identification of genetic variants. A total of 227 patients underwent panel testing at our center and 67 patients (29.5 %) had variants identified, with 8 (3.5 %) having multiple variants. Overall, 44 patients (19.4 %) had a variant of uncertain significance (VUS) and 28 patients (12.3 %) had a pathogenic variant detected, with 10 (4.4 %) having pathogenic variants in highly penetrant genes. We found no statistical difference in patient familial and personal cancer history, age, rural status, Ashkenazi Jewish ancestry, insurance coverage and prior single-gene testing among those with pathogenic, VUS and negative panel testing results. There were no predictors of pathogenic variants on regression analysis. Panel testing changed cancer screening and management guidelines from that expected based on family history alone in 13.2 % of patients. Ultimately, cancer panel testing does yield critical information not identified by traditional single gene testing but maximal utility through a broad range of personal and family histories requires improved interpretation of variants. PMID- 27401693 TI - Photoelectrochemical study of p-GaP(100)|ZnO|AuNP devices: strategies for enhanced electron transfer and aqueous catalysis. AB - We report a photocathode device consisting of GaP, a metal oxide (Al2O3 or ZnO), a phosphonate-C12-thiol monolayer, and gold nanoparticles (AuNPs). The AuNPs enhance electron transfer: in non-aqueous electrochemistry (EtV(2+) in MeCN), p GaP|Al2O3|O3PC12S|AuNP and ...ZnO|...|AuNP rescued the photocurrent (24%, 59% of Jmax-etch). Aqueous experiments (CO2 saturated KCl) using the optimized ZnO functionalized device exhibited H(+) -> H2 (FY = 66%) and CO2 -> CO (FY = 6%). PMID- 27401691 TI - Intensified colonisation screening according to the recommendations of the German Commission for Hospital Hygiene and Infectious Diseases Prevention (KRINKO): identification and containment of a Serratia marcescens outbreak in the neonatal intensive care unit, Jena, Germany, 2013-2014. AB - PURPOSE: In 2013, the German Commission for Hospital Hygiene and Infectious Disease Prevention (KRINKO) stated that extending weekly colonisation screening from very low birth weight (VLBW) infants (<1500 g) to all patients in the Neonatal Intensive Care Unit (NICU) might be useful. METHODS: After implementing this recommendation, we detected a previously unnoticed cluster of Serratia marcescens. Strains were typed by Pulsed Field Gel Electrophoresis (PFGE). RESULTS: Over 6 months, 19 out of 159 infants acquired S. marcescens. Twelve of the nineteen patients with S. marcescens were non-VLBW infants, and they were colonised significantly earlier than were VLBW infants (median 17 vs. 28 days; p < 0.01). Molecular typing revealed a polyclonal outbreak with multiple strain types leading to one or two transmissions each and a dominating outbreak strains being involved in an explosive outbreak involving eight neonates. CONCLUSION: The revised KRINKO recommendation may help identify unnoticed outbreaks. Colonised non-VLBW patients may be an underestimated source of S. marcescens. PMID- 27401694 TI - Identifying symptoms in chronic venous diseases. PMID- 27401695 TI - Ureteral kinking during cystocele correction trough UpHold((r)) subvesical mesh: case report. PMID- 27401696 TI - Lymphangioma of the ovary: etiology and management. AB - Lymphangioma of the ovary is an extremely rare lesion. It was first described in 1908 [1] and there is only 19 cases reports in a 50-year literature survey [2]. Lymphangiomas are benign congenital malformations of lymphatic system. They are thought to happen due to obstruction of local lymph flow system and they can occur anywhere in the skin and the mucous membranes. Most common sites are the head and the neck and sometimes they can be found in the intestines, the pancreas and the mesentery. Lymphangioma of the ovary is a very rare tumor. Typically, lymphangiomas are slow-growing tumors that remain asymptomatic for a long time, with the tumor being identified incidentally during histopathological examination after excision. A 36-year-old women who consulted our department for infertility for 2 years. The systematic ultrasound examination reveals a right ovarian mass. The histologic analysis confirmed the diagnosis of cystic lymphangioma of the right ovary. She was planned for total laparoscopic tumorectomy with removal of all ovarian mass. The evolution was good for one year within Clinical and ultrasound monitoring. We report through this case report a review of the literature. PMID- 27401697 TI - Evaluation of cerebral blood flow in acute ischemic stroke patients with atrial fibrillation: A sonographic study. AB - BACKGROUND/PURPOSE: Although cerebral emboli are a frequent cause of cardiogenic stroke, the possibility of a reduction in cerebral perfusion consequent to arrhythmia or impaired cardiac function should be considered in patients with atrial fibrillation (AF). METHODS: We reviewed sonographic studies and clinical features of patients with acute ischemic stroke. A total of 144 patients with AF and 144 age- and sex-matched patients with small vessel occlusion but without AF were included. RESULTS: Patients with AF had significantly lower peak systolic velocity (PSV), mean velocity, flow volume (p < 0.001), and end-diastolic velocity (p = 0.035) of the internal carotid artery (ICA); significantly lower cerebral blood flow (p < 0.001); and lower flow velocities of the middle cerebral artery (p < 0.01) than patients with small vessel occlusion but without AF. In patients with AF, there was an inverse linear correlation between ICA end diastolic velocity, mean velocity (p < 0.001), flow volume (p = 0.025), middle cerebral artery flow velocities (p < 0.05), and age. Cardiac ejection fraction had a positive linear correlation with ICA PSV (p = 0.016) but an inverse correlation with the heart rate (p = 0.009). There was a significant decline in PSV (p = 0.002), resistance index (p < 0.001), and flow volume (p = 0.0121) of the ICA as well as cerebral blood flow (p = 0.009) as the heart rate increased. CONCLUSION: Cerebral blood flow is markedly reduced in ischemic stroke patients with AF as compared with that in patients with small vessel disease but without AF. PMID- 27401698 TI - Preadmission tracheostomy is associated with better outcomes in patients with prolonged mechanical ventilation in the postintensive care respiratory care setting. AB - BACKGROUND/PURPOSE: Prolonged mechanical ventilation (PMV) is the most common situation where tracheostomy is indicated for intensive care unit (ICU) patients. However, it is unknown if this procedure confers survival benefits on PMV patients in a post-ICU setting. METHODS: Patients who were admitted to the specialized weaning unit from 2005 to 2008 and received PMV were included in this study. On admission, data pertaining to patient characteristics, physiologic status, and type of artificial airway (tracheostomy vs. no tracheostomy) were obtained. Outcomes of tracheostomized and nontracheostomized patients were evaluated using multivariate Cox proportional hazards and propensity score matching models. The primary outcome of interest was 1-year survival. RESULTS: A total of 401 patients (mean age 74.4 years, 204 male) were identified. In multivariate analyses, higher Acute Physiology and Chronic Health Evaluation II score [hazard ratio (HR) = 1.061, 95% confidence interval (CI) = 1.016-1.107] and presence of comorbidities, including congestive heart failure (HR = 1.562, 95% CI = 1.119-2.181), malignancy (HR = 1.942, 95% CI = 1.306-2.885), and liver cirrhosis (HR = 2.373, 95% CI = 1.015-5.544), were independently associated with 1-year mortality. An association between having tracheostomy and a better 1-year outcome was observed (HR = 0.625, 95% CI = 0.453-0.863). The matched cohort study also demonstrated a favorable 1-year survival for tracheostomized patients, and these patients had significantly lower in-hospital mortality (24% vs. 36%, p = 0.049) and risk of ventilator-associated pneumonia (10% vs. 20%, p = 0.030) than nontracheostomized ones. CONCLUSION: Preadmission tracheostomy may be associated with better outcomes of PMV patients in a post-ICU respiratory care setting. The findings suggest that this procedure should be recommended before PMV patients are transferred to specialized weaning units. PMID- 27401699 TI - In memoriam - Hans G. Truper (1936-2016). PMID- 27401700 TI - Initial experience in uniportal subxiphoid video-assisted thoracoscopic surgery for major lung resections. AB - OBJECTIVES: Uniportal subxiphoid video-assisted thoracoscopic (SVATS) surgery for major lung resections is a new approach, but clinical evidence is lacking. The aim of this study was to examine our experience with the use of the uniportal subxiphoid approach in video-assisted thoracoscopic (VATS) major lung resections and lymph node dissections. METHODS: From October 2014 to August 2015, 153 patients with early-stage non-small-cell lung carcinoma (NSCLC) and benign disease underwent uniportal subxiphoid VATS major lung resections. Patients were placed in a lateral position with 60-70 degrees inclination, and a 4- to 5-cm midline median or transverse incision was made below the sternocostal triangle. A 10-mm 30 degrees video camera and VATS instruments were used through the same single incision. Perioperative variables and outcomes were collected prospectively and analysed retrospectively. RESULTS: Of the 153 patients who underwent surgery with the uniportal subxiphoid VATS approach, 105 had lobectomies and 48 had segmental resections; 135 cases of lung cancer and 18 cases of benign pulmonary disease were noted. Right upper lobectomy was the most common procedure (51%), and left upper lobectomy was the most time-consuming procedure (190 +/- 21 min). The mean operating time was 166.9 +/- 12.6 min; the average volume of blood loss was 127.5 +/- 27.6 ml. In patients with lung cancer, the mean total number of lymph node stations explored was 3.4 +/- 0.8. The duration of chest drain use was 2.6 +/- 0.2 days. The length of hospital stay was 4.3 +/- 0.4 days. Perioperative arrhythmia was the most common complication (13% of cases). Prolonged air leak was the cause of prolonged hospital stay. Five cases were converted to conventional VATS due to technical difficulties, and eight cases were converted to thoracotomy due to major bleeding. Postoperative 30 day mortality was zero and there were no re-admissions. All cases had a R0 complete cancer resection on histology. CONCLUSIONS: Uniportal subxiphoid VATS lobectomy/segmentectomy is a feasible and safe procedure for early-stage lung cancer and benign disease. PMID- 27401701 TI - Left ventricular restoration in heart failure: rebirth due to interventional devices? PMID- 27401703 TI - Impact of mode of failure and end-organ dysfunction on the survival of adult Fontan patients undergoing cardiac transplantation. AB - OBJECTIVES: Adults with failing Fontan circulation (FFC) represent a heterogeneous, high-risk group for cardiac transplantation with poor reported outcomes. We studied the impact of mode of Fontan failure (preserved versus impaired systolic ventricular function) and end-organ dysfunction on early survival in adults undergoing cardiac transplantation for FFC. METHODS: A single centre, retrospective study of 26 adults (>=16 years) with FFC undergoing cardiac transplantation between 1990 and 2015. Patients were classified by the presence or absence of preserved systolic ventricular function (PVF). End-organ dysfunction was assessed by serum markers, including albumin, liver ultrasound and the presence of varices, ascites, splenomegaly and thrombocytopaenia (VAST score for portal hypertension). RESULTS: Thirty-day survival rate for the entire cohort was 69.2%, with 76.2% survival for the recent era. One-year Kaplan-Meier survival rate was 65.4%. Actuarial survival was poorer in those with PVF or heterotaxy (P = 0.01; log-rank test). Cox multivariable regression analysis confirmed PVF as an independent predictor for death (odds ratio, OR 5.38; confidence interval, CI 1.08-26.96; P = 0.04). In examining the PVF subset further, these patients had significantly higher VAST and liver ultrasound scores and lower serum albumin, compared with patients with impaired function. Patients with PVF and >=moderate liver fibrosis on ultrasound or VAST score >=2 accounted for two-thirds of the total mortality. CONCLUSIONS: Favourable cardiac transplantation outcomes can be achieved in adults with failing Fontan circulation. Patients with PVF may represent a distinct subset with more perturbed failing Fontan physiology and higher cardiac transplant mortality. We continue, however, to evolve and refine our strategies and are optimistic concerning future improvement in outcomes even in those with PVF. PMID- 27401704 TI - Factors associated with survival in patients with oesophageal cancer who achieve pathological complete response after chemoradiotherapy: a nationwide population based study. AB - OBJECTIVES: Few data are currently available on the factors associated with survival in oesophageal cancer patients who achieve pathological complete response (pCR) after chemoradiotherapy (CRT). Using a nationwide database, we investigated the predictors of survival in this patient group. METHODS: Data were retrieved from the Taiwan Cancer Registry to identify patients with oesophageal squamous cell carcinoma (OSCC) who achieved pCR after CRT followed by oesophagectomy between 2008 and 2013. The median number of dissected nodes (20) was used as the cut-off to classify the extent of lymph node dissection (LND). Tumour location was defined according to the seventh edition of the American Joint Committee on Cancer staging system. Cox proportional hazard regression analyses were used to identify factors associated with survival. RESULTS: Of the 1103 patients who underwent CRT followed by surgery, 319 (28.9%) achieved pCR. Thirty- and 90-day mortality rates were 3.5 and 4.7%, respectively. The 3-year overall survival rate was 55.9%. Multivariate Cox survival analysis identified age >=55 years [hazard ratio (HR): 1.72, 95% confidence interval (CI): 1.07 to 2.78, P = 0.025], an LND number of <20 (HR: 1.62, 95% CI: 1.01 to 2.61, P = 0.047) and lesions located in the upper third (HR: 2.35, 95% CI: 1.18 to 4.65, P = 0.015) as adverse prognostic factors for survival in pCR patients. CONCLUSIONS: Patient age >=55 years, upper third lesions and an LND number of <20 are adverse prognostic factors in OSCC patients who achieve pCR following CRT. High-risk patients should be strictly followed. PMID- 27401705 TI - Significance of R1-resection at the bronchial margin after surgery for non-small cell lung cancer. AB - OBJECTIVES: We aimed to evaluate the significance of microscopic residual disease at the bronchial resection margin (R1-BRM) after curative surgery for non-small cell lung cancer (NSCLC). METHODS: Retrospective review was performed on 1800 patients from 1994 to 2012. We compared recurrence and survival between 1740 patients with R0-resection at the BRM (R0-BRM) and 60 patients with R1-resection at the BRM (R1-BRM), comprising 18 cases of mucosal carcinoma in situ (R1-CIS) and 42 cases of extramucosal residual disease (R1-EMD). RESULTS: Stump recurrence occurred in 43 patients. The 5-year cumulative incidence of stump recurrence in group R0, R1-CIS and R1-EMD was 3.1, 5.6 and 12.2%, respectively. Significant differences of stump recurrence were observed between the groups (R0 versus R1 CIS, P = 0.008; R0 versus R1-EMD, P = 0.007). In Stage IB or II disease, the overall survival rate for R1-EMD was significantly lower than that for R0-BRM (P = 0.014), whereas the difference in overall survival rate between the R1-CIS group and the R0-BRM was not significant (P = 0.37). In Stage IIIA disease, the overall survival rates for R1-CIS (P = 0.87) and R1-EMD (P = 0.45) were not significantly different from that for R0-BRM. CONCLUSIONS: R1-BRM comprises a higher rate of stump recurrence, compared with that of R0-BRM. Herein, R1-EMD was associated with poor overall survival in Stage IB/II disease. In Stage IIIA disease, R1-BRM showed similar overall survival rate to that for R0-BRM, although the number of patients was too small to draw definitive conclusions thereon. PMID- 27401706 TI - ESTS Presidential Address: Books, songs and thoracic surgery. PMID- 27401707 TI - Non-intubated video-assisted thoracic surgery: breaking down paradigms. PMID- 27401708 TI - Reply to Armenta-Flores et al. PMID- 27401709 TI - Early, dedicated follow-up and treatment of pleural effusions enhance the recovery rate after open cardiac surgery: results from a randomized, clinical trial. AB - OBJECTIVES: Recent studies conclude that cardiac surgery patients are prone to both mortality and morbidity in the weeks after discharge. Complications such as pleural and pericardial effusions may influence physical recovery due to symptoms such as dyspnoea, chest pain and fatigue. Dedicated follow-up and timely treatment of postoperative complications are suggested. METHODS: A randomized, controlled intervention trial including 76 patients, in the ratio of 1 : 1. Patients scheduled for elective on-pump coronary artery bypass grafting and/or aortic valve replacement were eligible for inclusion. Patients were randomized to either standard postoperative care or complementary follow-up visits with clinical examinations, focused chest sonography and protocol-driven thoracentesis if applicable. Primary outcomes were the mean change in walking distance, peak expiratory flow and EuroQOL from baseline to 30 days after surgery. RESULTS: The mean difference in walking distance after 30 days was 15% (65 +/- 22 m) between groups, P = 0.017. No differences were found in the peak expiratory flow or EuroQOL. In patients with pleural effusion, walking distance improved by 22% after thoracentesis (81 +/- 42 m), P < 0.0001, and peak expiratory flow improved by 26% (1.1 +/- 1.2 l/min), P < 0.001. CONCLUSIONS: Supplemental dedicated follow up and treatment of postoperative effusions enhance recovery by 15% compared with standard care, measured by improvement in the walking distance 1 month after cardiac surgery. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02045641. UNIQUE IDENTIFIER: NCT02045641. PMID- 27401711 TI - Author Reply. PMID- 27401710 TI - A successful management of infection of the left ventricular assist device by pump exchange: conversion from DuraHeart to Jarvik 2000. AB - We successfully controlled infection of a left ventricular assist device by performing pump exchange. A 53-year-old man was implanted with DuraHeart for ischemic cardiomyopathy as a bridge to transplantation. Two years later, he was hospitalized with the diagnosis of driveline infection. The blood cultures detected Pseudomonas aeruginosa. During the admission, he developed brain hemorrhage perhaps due to septic emboli. The chest computed tomography scan revealed a small defect inside the outflow graft of the DuraHeart, which was highly suspected of vegetation. He underwent pump exchange, from DuraHeart to Jarvik 2000 with concomitant omentopexy. His postoperative course was uneventful, and he was discharged with no sequela of the brain hemorrhage. Four months after the pump exchange, he successfully underwent heart transplantation. No infectious tissue was observed in the pericardial space at the time of heart transplantation. Pump exchange is an effective way to manage refractory left ventricular assist device infection, and the timing of surgical intervention is of great importance. PMID- 27401712 TI - Editorial Comment. PMID- 27401713 TI - Author Reply. PMID- 27401714 TI - Editorial Comment. PMID- 27401715 TI - Editorial Comment. PMID- 27401716 TI - Why are estimates of the strength and direction of natural selection from wild populations not congruent with observed rates of phenotypic change? AB - Observing adaptive evolution is difficult. In the fossil record, phenotypic evolution happens much more slowly than in artificial selection experiments or in experimental evolution. Yet measures of selection on phenotypic traits, with high heritabilities, suggest that phenotypic evolution should also be rapid in the wild, and this discrepancy often remains even after accounting for correlations between different traits (i.e. making predictions using the multivariate version of the breeder's equation). Are fitness correlations with quantitative traits adequate measures of selection in the wild? We should instead view fitnesses as average properties of genotypes, while acknowledging that they can be environment dependent. Populations will tend to remain at fitness equilibria, once these are attained, and phenotypes will then be stable. Thus, studying the causes of adaptive change at a genotypic rather than phenotypic level may reveal that, typically, it is occurring too slowly to be easily observed. PMID- 27401717 TI - Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells. AB - Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins. PMID- 27401718 TI - Whole-transcriptome analysis of chordoma of the skull base. AB - Fourteen skull base chordoma specimens and three normal specimens were microdissected from paraffin-embedded tissue. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using whole-transcriptome shotgun sequencing. Using strict criteria, 294 differentially expressed transcripts were found, with 28 % upregulated and 72 % downregulated. The transcripts were annotated using NCBI Entrez Gene and computationally analyzed with the Ingenuity Pathway Analysis program. From these significantly changed expressions, the analysis identified 222 cancer-related transcripts. These 294 differentially expressed genes and non-coding RNA transcripts provide here a set to specifically define skull base chordomas and to identify novel and potentially important targets for diagnosis, prognosis, and therapy of this cancer. Significance Genomic profiling to subtype skull base chordoma reveals potential candidates for specific biomarkers, with validation by IHC for selected candidates. The highly expressed developmental genes T, LMX1A, ZIC4, LHX4, and HOXA1 may be potential drivers of this disease. PMID- 27401719 TI - Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer. AB - Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications. PMID- 27401720 TI - Age-specific risk factors for incident disability in activities of daily living among middle-aged and elderly community-dwelling Japanese women during an 8-9 year follow up: The Hizen-Oshima study. AB - AIM: The purposes of the present study were to investigate risk factors for incident disability in activities of daily living (ADL) among middle-aged and older women, and to determine whether there are differences in risk factors according to age groups. METHODS: The participants were 264 Japanese women aged 40 years and older. A self-administered questionnaire was used to survey participants about difficulty in carrying out selected basic and instrumental ADL at baseline and at follow up. ADL disability was defined as difficulty carrying out three or more ADL. Information on knee joint or back pain and comorbidities (heart disease, lung disease, stroke or diabetes mellitus) was obtained using a self-administered questionnaire at baseline. Physical performance measurements (grip strength, chair stand time, rapid walking speed and functional reach) were also carried out at baseline. RESULTS: The prevalence of incident ADL disability was 44 (27.5%) in women aged 40-64 years, and 57 (54.8%) in women aged >=65 years (P < 0.001). Multiple logistic regression analysis showed that decreased grip strength and having pain were significantly associated with a higher risk for incident ADL disability among women aged 40-64 years. For women aged >=65 years, decreased rapid walking speed, having a comorbidity and having pain were associated with incident ADL disability. CONCLUSIONS: The present study showed that a different set of risk factors was associated with incident ADL disability among women aged 40-64 years and women aged >=65 years. Age-specific screening and intervention strategies are necessary for effective prevention of incident ADL disability. Geriatr Gerontol Int 2017; 17: 1096-1101. PMID- 27401721 TI - Peripheral neuropathy in patients with myotonic dystrophy type 2. AB - OBJECTIVES: Myotonic dystrophy type 2 (dystrophia myotonica type 2-DM2) is an autosomal dominant multi-organ disorder. The involvement of the peripheral nervous system was found in 25%-45% of patients with myotonic dystrophy type 1, although limited data are available concerning polyneuropathy in patients with DM2, which was the aim of this study with a thorough presentation of the cases with peripheral neuropathy. MATERIAL AND METHODS: Patients with genetically confirmed DM2 underwent motor nerve conduction studies of the median, ulnar, tibial and fibular nerves and sensory nerve conduction studies of the median (second finger), ulnar (fifth finger), radial (forearm) and sural nerves. RESULTS: Seventeen adult patients with DM2 participated in the study. Fifty-three percent (9/17) of our patients had abnormality of one or more attributes (latency, amplitude or conduction velocity) in two or more separate nerves. Four types of neuropathies were found: (i) predominantly axonal motor and sensory polyneuropathy, (ii) motor polyneuropathy, (iii) predominantly demyelinating motor and sensory polyneuropathy and (iv) mutilating polyneuropathy with ulcers. The most common forms are axonal motor and sensory polyneuropathy (29%) and motor neuropathy (18% of all examined patients). No correlations were found between the presence of neuropathy and age, CCTG repeats, blood glucose or HbA1C. CONCLUSIONS: Peripheral neuropathy is common in patients with DM2 and presents one of the multisystemic manifestations of DM2. PMID- 27401722 TI - Dark adaptation in relation to choroidal thickness in healthy young subjects: a cross-sectional, observational study. AB - BACKGROUND: Dark adaptation is an energy-requiring process in the outer retina nourished by the profusely perfused choroid. We hypothesized that variations in choroidal thickness might affect the rate of dark adaptation. METHOD: Cross sectional, observational study of 42 healthy university students (mean age 25 +/- 2.0 years, 29 % men) who were examined using an abbreviated automated dark adaptometry protocol with a 2 degrees diameter stimulus centered 5 degrees above the point of fixation. The early, linear part of the rod-mediated dark adaptation curve was analyzed to extract the time required to reach a sensitivity of 5.0 * 10(-3) cd/m2 (time to rod intercept) and the slope (rod adaptation rate). The choroid was imaged using enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). RESULTS: The time to the rod intercept was 7.3 +/- 0.94 (range 5.1 - 10.2) min. Choroidal thickness 2.5 degrees above the fovea was 348 +/- 104 (range 153-534) MUm. There was no significant correlation between any of the two measures of rod-mediated dark adaptation and choroidal thickness (time to rod intercept versus choroidal thickness 0.072 (CI95 -0.23 to 0.38) min/100 MUm, P = 0.64, adjusted for age and sex). There was no association between the time-to-rod-intercept or the dark adaptation rate and axial length, refraction, gender or age. CONCLUSION: Choroidal thickness, refraction and ocular axial length had no detectable effect on rod-mediated dark adaptation in healthy young subjects. Our results do not support that variations in dark adaptation can be attributed to variations in choroidal thickness. PMID- 27401723 TI - Vascular Density in Retina and Choriocapillaris as Measured by Optical Coherence Tomography Angiography. PMID- 27401724 TI - Distinct Responsiveness to Intravitreal Ranibizumab Therapy in Polypoidal Choroidal Vasculopathy With Single or Multiple Polyps. PMID- 27401725 TI - Reply. PMID- 27401726 TI - Clinical Efficacy and Safety of Ranibizumab Versus Dexamethasone for Central Retinal Vein Occlusion (COMRADE C): A European Label Study. PMID- 27401728 TI - Pubertal timing and bone phenotype in early old age: findings from a British birth cohort study. AB - OBJECTIVES: To investigate the effect of pubertal timing, assessed in adolescence, on bone size, strength and density in men and women in early old age. DESIGN: A British birth cohort study with prospective indicators of pubertal timing based on age at menarche, clinical assessment of pubertal stage, and growth tempo from serial height measures, and bone measures derived from peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) at 60-64 years of age among 866 women and 792 men. METHODS: A first set of regression models investigated the relationships between pubertal timing and bone size, strength and density, adjusting for current height and weight, smoking and adult socioeconomic position. To make an equivalent comparison between men and women, the percentage difference in bone outcomes was calculated for a 5-year difference in age at menarche, and in men a comparison between those who were fully mature or pre-adolescent at 14.5 years. A second set of models investigated the percentage difference in bone outcomes for a 5-year difference in timing of peak height velocity (height tempo) derived from longitudinal growth modelling (Superimposition by Translation and Rotation model; SITAR). RESULTS: After adjustment for current height and weight, a 5-year increase in age at menarche was associated with an 8% [95% confidence interval (CI) -17%, 0.5%, P = 0.07) lower trabecular volumetric bone mineral density (vBMD); men who were pre-adolescent at 14.5 years had a 9%, (95% CI -14%, -4%; P = 0.001) lower trabecular vBMD compared with those who had been fully mature. Other confounders did not attenuate these estimates further. Patterns of association were similar but somewhat weaker for lumbar spine and total hip areal BMD. Age at peak height velocity was associated with even larger differences in BMD in men and women, and was negatively associated with bone size and strength. CONCLUSIONS: The association between later puberty and lower BMD persists into early old age. The 9-10% lower trabecular vBMD in later compared with earlier maturers could be clinically important given a rate of bone loss from midlife of 1-2% a year and the negative association between BMD and fracture. PMID- 27401730 TI - Commentary: Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms. PMID- 27401729 TI - Childhood socioeconomic disadvantage is associated with lower mortality in older Japanese men: the JAGES cohort study. AB - BACKGROUND: Childhood socioeconomic disadvantage has been previously linked to increased mortality risk in adulthood. However, most previous studies have focused on middle-aged adults in Western contexts. Here, we sought to examine the association between childhood socioeconomic status (SES) and mortality among healthy older Japanese adults. METHODS: We conducted a 3-year follow-up of participants in the Japan Gerontological Evaluation Study (JAGES), a population based cohort of 65- to 103-year-old Japanese adults. Childhood SES was assessed by survey at baseline. Mortality from 2010 to 2013 was analysed for 15 449 respondents (7143 men and 8306 women). Cox regression models were used to estimate hazard ratios (HR) for risk of death. RESULTS: A total of 754 deaths occurred during the 3-year follow-up. Lower childhood SES was significantly associated with lower mortality in men, but not in women. Compared with men growing up in more advantaged childhood socioeconomic circumstances, the age adjusted HR for men from low childhood SES backgrounds was 0.75 [95% confidence interval (CI): 0.56-1.00]. The association remained significant after adjustment for height, education, adult SES, municipalities of residence, health behaviours, disease status and current social relationships (HR = 0.64; 95% CI 0.47-0.87). This association was stronger among men aged 75 years or older, HR = 0.67 (95% CI: 0.47-0.95), compared with men aged 65-74 years, HR = 0.90 (95% CI: 0.54 1.51). CONCLUSIONS: Childhood socioeconomic disadvantage is associated with lower mortality among men aged 75 years or older, which may be due to selective survival, or alternatively to childhood physical training or postwar calorie restriction in this generation of Japanese males. PMID- 27401731 TI - Response to Letter by Prof. C.B.B. Bunker. PMID- 27401727 TI - Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study. AB - BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence. PMID- 27401732 TI - Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research. AB - BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups. PMID- 27401734 TI - The impact of contemporary multidisciplinary meetings on workload at a tertiary level hospital. AB - BACKGROUND: In recent years, multidisciplinary meetings (MDMs) have become the standard of patient care in oncologic and other speciality care pathways. The number, complexity, and diverse source of imaging studies presented continue to expand rapidly. True multidisciplinary input requires parallel support from other colleagues and diagnostic services. It is now recognised that this is the appropriate forum for key decision making and education in care algorithms, though service plans make little or no accommodation of their expanding role in addition to existing services. AIMS: We tried to objectively quantify one element of this burgeoning service. METHODS: Data were retrospectively gathered over a 6 month period, and a 5 week prospective study was then performed to examine the workload in further detail. RESULTS: Retrospectively, 199 meetings were held with 2253 clinical cases reviewed over 26 weeks. Prospectively, 52 meetings were held over 5 weeks for 13 clinical specialty areas. There were 1038 clinical case discussions. There were a total of 2122 documented individual imaging studies reviewed. Specialist registrar preparation time was 55 h (11 per week). Consultant preparation time was 67.75 h (13.55 per week). Delivery time was 57.25 h (11.45 per week). CONCLUSION: The complexity and range of cases at MDMs continue to expand, serving local and national needs, though service plans do not acknowledge their role in the working day. Our study shows just one element that clearly signals a need to take account of the new methods of delivering modern healthcare. PMID- 27401733 TI - Right ventricular dysfunction as predictor of longer hospital stay in patients with acute decompensated heart failure: a prospective study in Indonesian population. AB - BACKGROUND: Hospital length of stay (LOS) is a key determinant of heart failure hospitalization costs. Longer LOS is associated with lower quality of care measures and higher rates of readmission and mortality. Right ventricular (RV) dysfunction predicted poor outcomes in patients with stable chronic heart failure (CHF), however, its prognostic value in the acute decompensated heart failure (ADHF) patients has not been sufficiently clarified. This study investigated the prognostic value of RV dysfunction in predicting longer LOS in ADHF patients. METHODS: A prospective cohort study was conducted in National Cardiovascular Center Harapan Kita to all patients admitted with ADHF. Clinical data and baseline RV function assessed by tricuspid annular plane systolic excursion (TAPSE) were collected. Clinical comorbidities including malnutrition, pneumonia and worsening renal function (WRF) were monitored during hospitalization. The primary outcome was hospital LOS. Cox regression analysis was used to identify independent predictors for longer LOS. RESULTS: Two hundred and fifty-nine ADHF patients were included in this cohort study. On time-to-event analysis, diastolic blood pressure (HR = 1.011; 95 % CI = 1.004-1.018; p = 0.002), hemoglobin levels (HR = 1.102; 95 % CI = 1.045-1.162; p < 0.001), RV function (HR = 0.659; 95 % CI = 0.506-0.857; p = 0.002), WRF (HR = 2.015; 95 % CI = 1.520-2.670; p < 0.001) and malnutrition (HR = 5.965; 95 % CI = 4.402-8.082; p < 0.001) were associated with longer LOS. In a multivariate Cox regression model, RV function (HR = 0.466; 95 % CI = 0.238-0.915; p = 0.026), WRF (HR = 2.985; 95 % CI = 2.032-4.386; p < 0.001) and malnutrition (HR = 7.479; 95 % CI = 5.071-11.030; p < 0.001) were the independent predictors of longer hospital LOS. Based on the median TAPSE values, patients with TAPSE <= 16 mm had significantly longer LOS (HR = 2.227; 95 % CI = 1.103-4.494; p = 0.026) compared to those with TAPSE > 16 mm. CONCLUSIONS: Right ventricular dysfunction, WRF and malnutrition are important predictors of longer LOS. This is the first study to describe that in ADHF patients, lower the TAPSE resulted in longer the LOS. PMID- 27401735 TI - Postpartum dyslipidaemia in women diagnosed with gestational diabetes mellitus. AB - BACKGROUND: Diabetes mellitus is a known risk factor for cardiovascular disease which should prompt screening for other cardiovascular risk factors, including dyslipidaemia. Women diagnosed with gestational diabetes mellitus (GDM) are not routinely screened for cardiovascular risk factors. AIMS: The objective of this study was to determine the prevalence of dyslipidaemia postpartum in women with GDM. METHODS: The study was performed in a large university hospital. Women with GDM had a fasting lipid profile performed 6 weeks postnatally. Clinical details were obtained from the medical records. Lipid results in our cohort were compared with healthy women of the same age. RESULTS: The overall prevalence of postpartum dyslipidaemia was 52 % (n = 51). Total cholesterol was raised in 44 % (n = 43), low-density lipoprotein was raised in 33 % (n = 32) and triglycerides were raised in 16 % (n = 16). Of the 51 women with dyslipidaemia, 73 % (n = 37) had more than one abnormality in their lipid profile. Four of the five women with an abnormal postpartum GTT had an abnormal lipid profile. Compared with healthy women of the same age, women with GDM had higher total cholesterol (p = 0.04), higher LDL (p = 0.003), higher triglycerides (p < 0.001) and lower HDL (p < 0.04). CONCLUSIONS: Women with GDM should be screened for dyslipidaemia postpartum and protective cardiovascular interventions offered where appropriate. PMID- 27401736 TI - Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica. AB - BACKGROUND: In neuromyelitis optica (NMO), one of the underlying pathogenic mechanisms is the formation of antigen-antibody complexes which can trigger an inflammatory response by inducing the infiltration of neutrophils in lesions. Epithelial neutrophil-activating peptide 78 (ENA 78), known as Chemokine (C-X-C motif) ligand 5 (CXCL5), belongs to the ELR-CXCL family. It recruits and activates neutrophils. The aim of this study was to evaluate ENA 78, IL-1beta and TNF-alpha plasma levels in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. METHODS: ENA 78, IL-1beta and TNF-alpha plasma levels were detected in 20 healthy controls (HC), 25 MS and 25 NMO patients using MILLIPLEX(r) map Human High Sensitivity Cytokine/Chemokine Panels. RESULTS: Plasma levels of ENA 78 were significantly higher in NMO patients than in HC (P < 0.001) and MS patients (P < 0.05). The NMO patients showed higher plasma levels of IL-1beta compared with HC (P < 0.01). Further, increased plasma levels of TNF-alpha were found in the MS (P < 0.05) and NMO patients (P < 0.001). In addition, NMO patients had higher Expanded Disability Status Scale (EDSS) scores compared with MS patients (P < 0.05). EDSS scores were correlated with plasma levels of ENA 78 in NMO patients (P < 0.05). There were no significant correlations between EDSS scores and plasma levels of ENA 78 in MS patients (P > 0.05). CONCLUSIONS: The overproduction of pro-inflammatory cytokines such as IL-1beta and TNF-alpha during the remission of NMO activates ENA 78, which in turn leads to neutrophil infiltration in lesions. ENA 78 plasma levels were correlated with EDSS scores in NMO patients. Elevated secretion of ENA 78 may be a critical step in neutrophil recruitment during the remission of NMO. PMID- 27401737 TI - Predictive value of the augmentation index derived vascular age in patients with newly diagnosed atherosclerosis. AB - Early detection of atherosclerosis, i.e., in occupational health screening programs could reduce the rate of cardiovascular events in the working population. Changes of the augmentation index (AIX) correlate with changes of the arterial stiffness induced by aging, atherosclerosis, or arterial hypertension and have a prognostic value for cardiovascular events. Their diagnostic yield should be increased by normalizing the AIX to age, in terms of a calculating the vascular age (VA). In this pilot study, 30 patients (mean age 65.3 +/- 8.8 years, 21 male) with suspected coronary heart disease underwent a duplex ultrasound of the carotid arteries and a measurement of the ankle brachial index in addition to the coronary angiography. The AIX was recorded with a portable device (Vascular Explorer), and the VA was calculated. Atherosclerosis was found in 24 patients. They were older than the patients without atherosclerosis, but there was no age dependency found for the distribution pattern or severity of atherosclerosis. In patients with findings of atherosclerosis, the calculated VA was higher than the chronological age, and these differences were significant in patients below 65 years of age. Comparing patients in higher blood pressure classes with patients in lower classes, significantly higher AIX, VA, and differences to the chronological age were found. The VA, deduced from the noninvasively obtained AIX, is a promising candidate for screening programs for atherosclerosis, i.e., in occupational health screening programs. PMID- 27401738 TI - Prominent QTc prolongation in a patient with a rare variant in the cardiac ryanodine receptor gene. AB - We report the case of a 12-year-old female patient with a history of four syncopal episodes related to exercise over 2 years and who showed prominent QTc prolongation on electrocardiogram; therefore, she was clinically diagnosed with long QT syndrome type-1. However, genetic analysis did not identify any LQT related genes but showed a rare missense variant in the cardiac ryanodine receptor gene. From the results of drug-loading tests, administration of oral propranolol was initiated; thereafter, she experienced no syncopal episodes. This is a case report demonstrating the "overlapping clinical features" of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. PMID- 27401739 TI - Aliskiren suppresses atrial electrical and structural remodeling in a canine model of atrial fibrillation. AB - Aliskiren, a direct renin inhibitor is expected to achieve sufficient suppression of renin-angiotensin system. We evaluated the effect of aliskiren on the electrical and structural remodeling in a canine atrial fibrillation (AF) model. Twenty-eight dogs were divided into three groups: (1) pacing control group (n = 12), with continuous atrial rapid pacing for 3 or 6 weeks, (2) pacing + aliskiren group (n = 12), with oral aliskiren (30 mg/kg/day), and (3) sham group (n = 4), no pacing nor drug administration. Electrophysiological properties and AF inducibility were evaluated every week. After the protocol, the left atrial tissue was sampled for the further histological and mRNA analysis. The electrical remodeling, AF inducibility, the left atrial enlargement and interstitial fibrosis were observed in pacing control group and were more prominent in the 6 week protocol (vs. 3 week, p < 0.05). The mRNA expressions of matricellular proteins exhibited upregulation in 3-week pacing control, but these upregulations became insignificant in 6 weeks. In contrast, collagen type 3 exhibited significant upregulation in 6 week but not in 3-week protocol. These changes were suppressed in the pacing + aliskiren group. Aliskiren suppressed the atrial remodeling in a canine AF model. This effect was accompanied by the suppression of tissue fibrosis. PMID- 27401740 TI - Assessment of vascular autonomic function using peripheral arterial tonometry. AB - Peripheral autonomic function is impaired in diabetic polyneuropathy. However, it is difficult to evaluate it due to the lack of non-invasive quantitative assessment. We aimed to establish a novel index to evaluate vascular autonomic function using reactive hyperemia peripheral arterial tonometry (RH-PAT), a widely performed endothelial function test. Sixty-five subjects were enrolled, including healthy subjects, cases with sympathetic nerve blockers, and diabetic patients. RH-PAT was performed with 5-min blood flow occlusion in unilateral arm. We calculated the reduction ratio of the post-occlusion pulse amplitude to the baseline in the non-occluded arm (RPN), with 1-min sliding window. In healthy subjects, RPN gradually increased with time-dependent manner. However, this phenomenon was eliminated in cases with sympathetic nerve blockers. Plasma concentration of norepinephrine was measured before and after the blood flow occlusion, which showed a significant increase. We then compared RPNs with the change in heart rate variability (HRV) parameters. RPN calculated at 5 min after the reperfusion had the highest correlation with the change in sympathetic HRV parameter, and thus, we named sympathetic hypoemia index (SHI). Finally, we studied the relationship between SHI and diabetes. SHI was significantly lower in diabetic patients than matched controls. SHI, a novel index derived from RH-PAT, represented the peripheral sympathetic activity. SHI may be useful for assessing the vascular autonomic activity in diabetic patients. PMID- 27401741 TI - Estimated glucose disposal rate and long-term survival in type 2 diabetes after coronary artery bypass grafting. AB - We performed a nationwide population-based cohort study to investigate the association between estimated glucose disposal rate (eGDR) and long-term survival after coronary artery bypass grafting (CABG) in patients with type 2 diabetes. All patients who underwent primary CABG in Sweden from 2006 to 2013 were identified from the SWEDEHEART register and by record linkage to the National Diabetes Register; all patients with type 2 diabetes were included and formed the study population. Patients were followed until 2013 through national registers for major adverse cardiovascular events and death from any cause. eGDR was calculated using waist circumference, hemoglobin A1c, and presence or the absence of hypertension. The association between eGDR and death was estimated using multivariable Cox regression. A total of 3256 patients were included. During a mean follow-up of 3.1 years (10,227 person-years), in total, 14 % patients died: 17 % (n = 186) in the 1st tertile (lowest eGDR), 14 % (n = 145) in the 2nd tertile, and 13 % (n = 133) in the 3rd tertile (highest eGDR). There was a significant association between eGDR and increased risk of death: adjusted hazard ratio (95 % confidence interval): 1.46 (1.12-1.90) for the 1st eGDR tertile compared to the 3rd and highest eGDR tertile. In conclusion, patients with type 2 diabetes who underwent CABG, a low eGDR, were associated with an increased risk of long-term all-cause mortality that was independent of other cardiovascular and metabolic risk factors. Insulin resistance measured by eGDR could be a useful risk marker in patients with type 2 diabetes and ischemic heart disease. PMID- 27401742 TI - Posterior urethral valves: are neonatal imaging findings predictive of renal function during early childhood? AB - BACKGROUND: Obstructive renal dysplasia as observed on US is associated with posterior urethral valves and is regarded as predicting poor renal functional outcome. OBJECTIVE: To investigate whether any characteristic of urinary tract imaging at birth is predictive of renal function in children with prenatally diagnosed posterior urethral valves. MATERIALS AND METHODS: We reviewed clinical data including renal function (at birth and up to 3 years of age) and clinical outcome (urinary infection, dialysis, renal transplantation). Imaging data included US (dilatation of the urinary tract, renal cortical echogenicity, signs of cystic dysplasia, urinoma) and cystourethrography findings (vesicoureteral reflux, bladder anomalies, presence of valves) from imaging performed directly after birth. RESULTS: We retrospectively studied 30 children. Three of the 30 (10%) were in renal failure by the age of 3 years. Twelve of 14 (85%) children with parenchymal anomalies (cortical hyperechogenicity or cystic changes) and 8/9 (89%) children with bilateral high-grade reflux had normal renal function at age 3 years. One child without cystic dysplasia or reflux had abnormal renal function from birth. None of the six children with urinoma developed renal failure by the age of 3 years. CONCLUSION: Presence of cortical hyperechogenicity, cystic changes or bilateral reflux cannot be considered prognostic of renal failure by the age of 3 years. PMID- 27401743 TI - Biological agents for giant cell arteritis: treat to target. PMID- 27401744 TI - Infliximab and CT-P13 immunogenicity assessment in PLANETAS and PLANETRAS main and extension studies: utility of laboratory methods description. PMID- 27401745 TI - Duplication of the inferior vena cava from a division of the left external iliac vein. AB - Duplication of the inferior vena cava was detected in a 71-year-old Thai male cadaver with unknown cause of death. Two inferior vena cavae located on each side of the lumbar vertebrae were identified. The right inferior vena cava was formed by fusion of the right and left common iliac veins and had a normal course, while the left inferior vena cava arose from the left branch of the left external iliac vein and ascended parallel to the abdominal aorta. To our knowledge, no similar case has been previously reported. The left inferior vena cava joined the left renal vein to become the preaortic trunk before joining the right inferior vena cava. Tributaries of the inferior vena cava were observed and followed. Development of the duplication of the inferior vena cava was reviewed. Anatomical and developmental comprehension of the duplication of the inferior vena cava is important for clinicians in planning for retroperitoneal surgery. PMID- 27401746 TI - Acupuncture for the treatment of trigger finger in adults: a prospective case series. AB - OBJECTIVE: To determine the effect of acupuncture performed at the synovial and ligamentous tendon sheath (A1 pulley site) on pain during snapping and the severity of the snapping phenomenon in patients with trigger finger. METHODS: In this observational study, changes in the patients' condition were compared before and after acupuncture treatment. Acupuncture was performed on 19 fingers of 15 patients. Acupuncture needles were inserted into the radial and ulnar sides of the flexor tendon at the A1 pulley of the affected finger. Treatment was performed daily up to a maximum of five times. Before and after each treatment, pain during snapping and the severity of snapping were evaluated using a visual analogue scale (VAS). RESULTS: VAS scores for pain and snapping severity were significantly improved immediately after the first treatment (p<0.001). Pain during snapping, assessed before each treatment, improved over time, reaching statistical significance from the second treatment onwards (p<0.001); similarly, a significant improvement in the severity of snapping was observed, also from the second treatment (p<0.001). Patients with clinically significant improvements (>=50%) in pain and snapping severity had a significantly shorter duration of the disorder than those with <50% improvement (p<0.05). CONCLUSIONS: Acupuncture at the impaired A1 pulley site may be an effective treatment for trigger finger. We postulate that acupuncture may reduce inflammation/swelling of the synovial membrane of the tendon sheath, which predominates when the disorder is of short duration. Further research is required to confirm the efficacy/effectiveness of acupuncture for trigger finger and its mechanisms of action. PMID- 27401747 TI - Electroacupuncture improves cognitive deficits and activates PPAR-gamma in a rat model of Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) is an age-associated neurodegenerative disorder that is associated with a progressive impairment of cognition. Acupuncture has protective effects, although the molecular mechanisms are largely unknown. The activation of peroxisome proliferator activated receptor gamma (PPAR gamma) has an impact on the pathogenesis of AD. OBJECTIVE: To test the hypothesis that electroacupuncture (EA) confers therapeutic benefits through activation of PPAR-gamma in a rat model of AD. METHODS: 80 male Sprague-Dawley rats were randomly divided into four groups (n=20 each): Control (healthy control group), Sham (sham-operated group), AD (untreated AD model group), and AD+EA (AD model group treated with EA). The AD model was induced in the latter two groups by injection of amyloid-beta (Abeta)1-40 into the hippocampal CA1 area bilaterally. EA was administered at GV20 and BL23 six times per week for 4 weeks. The rats' behaviour was examined using the Morris water maze test, and protein expression of Abeta, hyperphosphorylated tau protein (p-Tau), PPAR-gamma, and hyperphosphorylated p38 mitogen activated protein kinase (p38MAPK) in the hippocampal CA1 region was examined by immunohistochemistry and Western blotting. RESULTS: EA significantly improved cognitive deficits and reduced Abeta and p-Tau Ser404 protein concentrations in the hippocampal CA1 region. AD decreased PPAR gamma and increased p-p38MAPK, while EA significantly upregulated PPAR-gamma expression and significantly downregulated p-p38MAPK expression. CONCLUSIONS: Acupuncture at GV20 and BL23 might have a beneficial effect on rats with AD via activation of PPAR-gamma and inhibition of p-p38MAPK expression. PMID- 27401748 TI - Cancer risk is higher in years before and shortly after type 2 diabetes diagnosis, study shows. PMID- 27401749 TI - Oocyte-specific deletion of N-WASP does not affect oocyte polarity, but causes failure of meiosis II completion. AB - STUDY QUESTION: There is an unexplored physiological role of N-WASP (neural Wiskott-Aldrich syndrome protein) in oocyte maturation that prevents completion of second meiosis. SUMMARY ANSWER: In mice, N-WASP deletion did not affect oocyte polarity and asymmetric meiotic division in first meiosis, but did impair midbody formation and second meiosis completion. WHAT IS KNOWN ALREADY: N-WASP regulates actin dynamics and participates in various cell activities through the RHO-GTPase Arp2/3 (actin-related protein 2/3 complex) pathway, and specifically the Cdc42 (cell division cycle 42)-N-WASP-Arp2/3 pathway. Differences in the functions of Cdc42 have been obtained from in vitro compared to in vivo studies. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: By conditional knockout of N-WASP in mouse oocytes, we analyzed its in vivo functions by employing a variety of different methods including oocyte culture, immunofluorescent staining and live oocyte imaging. Each experiment was repeated at least three times, and data were analyzed by paired-samples t-test. MAIN RESULTS AND THE ROLE OF CHANCE: Oocyte-specific deletion of N-WASP did not affect the process of oocyte maturation including spindle formation, spindle migration, polarity establishment and maintenance, and homologous chromosome or sister chromatid segregation, but caused failure of cytokinesis completion during second meiosis (P < 0.001 compared to control). Further analysis showed that a defective midbody may be responsible for the failure of cytokinesis completion. LIMITATIONS, REASONS FOR CAUTION: The present study did not include a detailed analysis of the mechanisms underlying the results, which will require more extensive further investigations. WIDER IMPLICATIONS OF THE FINDINGS: N-WASP may play an important role in mediating and co-ordinating the activity of the spindle (midbody) and actin (contractile ring constriction) when cell division occurs. The findings are important for understanding the regulation of oocyte meiosis completion and failures in this process that affect oocyte quality. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by the National Basic Research Program of China (No. 2012CB944404) and the National Natural Science Foundation of China (Nos 30930065, 31371451, 31272260 and 31530049). There are no potential conflicts of interests. PMID- 27401750 TI - Outcome after polytrauma in a certified trauma network: comparing standard vs. maximum care facilities concept of the study and study protocol (POLYQUALY). AB - BACKGROUND: The aim of this study is to evaluate the performance of the first certified regional trauma network in Germany, the Trauma Network Eastern Bavaria (TNO) addressing the following specific research questions: Do standard and maximum care facilities produce comparable (risk-adjusted) levels of patient outcome? Does TNO outperform reference data provided by the German Trauma Register 2008? Does TNO comply with selected benchmarks derived from the S3 practice guideline? Which barriers and facilitators can be identified in the health care delivery processes for polytrauma patients? METHOD/DESIGN: The design is based on a prospective multicenter cohort study comparing two cohorts of polytrauma patients: those treated in maximum care facilities and those treated in standard care facilities. Patient recruitment will take place in the 25 TNO clinics. It is estimated that n = 1.100 patients will be assessed for eligibility within a two-year period and n = 800 will be included into the study and analysed. Main outcome measures include the TraumaRegisterQM form, which has been implemented in the clinical routine since 2009 and is filled in via a web-based data management system in participating hospitals on a mandatory basis. Furthermore, patient-reported outcome is assessed using the EQ-5D at 6, 12 and 24 months after trauma. Comparisons will be drawn between the two cohorts. Further standards of comparisons are secondary data derived from German Trauma Registry as well as benchmarks from German S3 guideline on polytrauma. The qualitative part of the study will be based on semi-standardized interviews and focus group discussions with health care providers within TNO. The goal of the qualitative analysis is to elucidate which facilitating and inhibiting forces influence cooperation and performance within the network. DISCUSSION: This is the first study to evaluate a certified trauma network within the German health care system using a unique combination of a quantitative (prospective cohort study) and a qualitative (in-depth facilitator/barrier analysis) approach. The information generated by this project will be used in two ways. Firstly, within the region the results of the study will help to optimize the pre-hospital and clinical management of polytrauma patients. Secondly, on a nationwide scale, influential decision-making bodies, such as the Ministries of Health, the Hospital Associations, sickness funds, insurance companies and professional societies, will be addressed. The results will not only be applicable to the region of Eastern Bavaria, but also in most other parts of Germany with a comparable infrastructure. TRIAL REGISTRATION: VfD_Polyqualy_12_001978 , 10.Jan.2013; German Clinical Trials Register DRKS00010039 , 18.02.2016. PMID- 27401751 TI - Transmission of trisomy decreases with maternal age in mouse models of Down syndrome, mirroring a phenomenon in human Down syndrome mothers. AB - BACKGROUND: Down syndrome incidence in humans increases dramatically with maternal age. This is mainly the result of increased meiotic errors, but factors such as differences in abortion rate may play a role as well. Since the meiotic error rate increases almost exponentially after a certain age, its contribution to the overall incidence aneuploidy may mask the contribution of other processes. RESULTS: To focus on such selection mechanisms we investigated transmission in trisomic females, using data from mouse models and from Down syndrome humans. In trisomic females the a-priori probability for trisomy is independent of meiotic errors and thus approximately constant in the early embryo. Despite this, the rate of transmission of the extra chromosome decreases with age in females of the Ts65Dn and, as we show, for the Tc1 mouse models for Down syndrome. Evaluating progeny of 73 Tc1 births and 112 Ts65Dn births from females aged 130 days to 250 days old showed that both models exhibit a 3-fold reduction of the probability to transmit the trisomy with increased maternal ageing. This is concurrent with a 2 fold reduction of litter size with maternal ageing. Furthermore, analysis of previously reported 30 births in Down syndrome women shows a similar tendency with an almost three fold reduction in the probability to have a Down syndrome child between a 20 and 30 years old Down syndrome woman. CONCLUSIONS: In the two types of mice models for Down syndrome that were used for this study, and in human Down syndrome, older females have significantly lower probability to transmit the trisomy to the offspring. Our findings, taken together with previous reports of decreased supportive environment of the older uterus, add support to the notion that an older uterus negatively selects the less fit trisomic embryos. PMID- 27401752 TI - RecBCD Enzyme "Chi Recognition" Mutants Recognize Chi Recombination Hotspots in the Right DNA Context. AB - RecBCD enzyme is a complex, three-subunit protein machine essential for the major pathway of DNA double-strand break repair and homologous recombination in Escherichia coli Upon encountering a Chi recombination-hotspot during DNA unwinding, RecBCD nicks DNA to produce a single-stranded DNA end onto which it loads RecA protein. Conformational changes that regulate RecBCD's helicase and nuclease activities are induced upon its interaction with Chi, defined historically as 5' GCTGGTGG 3'. Chi is thought to be recognized as single stranded DNA passing through a tunnel in RecC. To define the Chi recognition domain in RecC and thus the mechanism of the RecBCD-Chi interaction, we altered by random mutagenesis eight RecC amino acids lining the tunnel. We screened for loss of Chi activity with Chi at one site in bacteriophage lambda. The 25 recC mutants analyzed thoroughly had undetectable or strongly reduced Chi-hotspot activity with previously reported Chi sites. Remarkably, most of these mutants had readily detectable, and some nearly wild-type, activity with Chi at newly generated Chi sites. Like wild-type RecBCD, these mutants had Chi activity that responded dramatically (up to fivefold, equivalent to Chi's hotspot activity) to nucleotide changes flanking 5' GCTGGTGG 3'. Thus, these and previously published RecC mutants thought to be Chi-recognition mutants are actually Chi context dependence mutants. Our results fundamentally alter the view that Chi is a simple 8-bp sequence recognized by the RecC tunnel. We propose that Chi hotspots have dual nucleotide sequence interactions, with both the RecC tunnel and the RecB nuclease domain. PMID- 27401753 TI - Axonopathy in the Central Nervous System Is the Hallmark of Mice with a Novel Intragenic Null Mutation of Dystonin. AB - Dystonia musculorum is a neurodegenerative disorder caused by a mutation in the dystonin gene. It has been described in mice and humans where it is called hereditary sensory autonomic neuropathy. Mutated mice show severe movement disorders and die at the age of 3-4 weeks. This study describes the discovery and molecular, clinical, as well as pathological characterization of a new spontaneously occurring mutation in the dystonin gene in C57BL/6N mice. The mutation represents a 40-kb intragenic deletion allele of the dystonin gene on chromosome 1 with exactly defined deletion borders. It was demonstrated by Western blot, mass spectrometry, and immunohistology that mice with a homozygous mutation were entirely devoid of the dystonin protein. Pathomorphological lesions were restricted to the brain stem and spinal cord and consisted of swollen, argyrophilic axons and dilated myelin sheaths in the white matter and, less frequently, total chromatolysis of neurons in the gray matter. Axonal damage was detected by amyloid precursor protein and nonphosphorylated neurofilament immunohistology. Axonopathy in the central nervous system (CNS) represents the hallmark of this disease. Mice with the dystonin mutation also showed suppurative inflammation in the respiratory tract, presumably due to brain stem lesion associated food aspiration, whereas skeletal muscles showed no pathomorphological changes. This study describes a novel mutation in the dystonin gene in mice leading to axonopathy in the CNS. In further studies, this model may provide new insights into the pathogenesis of neurodegenerative diseases and may elucidate the complex interactions of dystonin with various other cellular proteins especially in the CNS. PMID- 27401754 TI - Genomics of Natural Populations: How Differentially Expressed Genes Shape the Evolution of Chromosomal Inversions in Drosophila pseudoobscura. AB - Chromosomal rearrangements can shape the structure of genetic variation in the genome directly through alteration of genes at breakpoints or indirectly by holding combinations of genetic variants together due to reduced recombination. The third chromosome of Drosophila pseudoobscura is a model system to test hypotheses about how rearrangements are established in populations because its third chromosome is polymorphic for >30 gene arrangements that were generated by a series of overlapping inversion mutations. Circumstantial evidence has suggested that these gene arrangements are selected. Despite the expected homogenizing effects of extensive gene flow, the frequencies of arrangements form gradients or clines in nature, which have been stable since the system was first described >80 years ago. Furthermore, multiple arrangements exist at appreciable frequencies across several ecological niches providing the opportunity for heterokaryotypes to form. In this study, we tested whether genes are differentially expressed among chromosome arrangements in first instar larvae, adult females and males. In addition, we asked whether transcriptional patterns in heterokaryotypes are dominant, semidominant, overdominant, or underdominant. We find evidence for a significant abundance of differentially expressed genes across the inverted regions of the third chromosome, including an enrichment of genes involved in sensory perception for males. We find the majority of loci show additivity in heterokaryotypes. Our results suggest that multiple genes have expression differences among arrangements that were either captured by the original inversion mutation or accumulated after it reached polymorphic frequencies, providing a potential source of genetic variation for selection to act upon. These data suggest that the inversions are favored because of their indirect effect of recombination suppression that has held different combinations of differentially expressed genes together in the various gene arrangement backgrounds. PMID- 27401755 TI - High rates of glucose utilization in the gas gland of Atlantic cod (Gadus morhua) are supported by GLUT1 and HK1b. AB - The gas gland of physoclistous fish utilizes glucose to generate lactic acid that leads to the off-loading of oxygen from haemoglobin. This study addresses characteristics of the first two steps in glucose utilization in the gas gland of Atlantic cod (Gadus morhua). Glucose metabolism by isolated gas gland cells was 12- and 170-fold higher, respectively, than that in heart and red blood cells (RBCs) as determined by the production of (3)H2O from [2-(3)H]glucose. In the gas gland, essentially all of the glucose consumed was converted to lactate. Glucose uptake in the gas gland shows a very high dependence upon facilitated transport as evidenced by saturation of uptake of 2-deoxyglucose at a low extracellular concentration and a requirement for high levels of cytochalasin B for uptake inhibition despite the high efficacy of this treatment in heart and RBCs. Glucose transport is via glucose transporter 1 (GLUT1), which is localized to the glandular cells. GLUT1 western blot analysis from whole-tissue lysates displayed a band with a relative molecular mass of 52 kDa, consistent with the deduced amino acid sequence. Levels of 52 kDa GLUT1 in the gas gland were 2.3- and 33 fold higher, respectively, than those in heart and RBCs, respectively. Glucose phosphorylation is catalysed by hexokinase Ib (HKIb), a paralogue that cannot bind to the outer mitochondrial membrane. Transcript levels of HKIb in the gas gland were 52- and 57-fold more abundant, respectively, than those in heart and RBCs. It appears that high levels of GLUT1 protein and an unusual isoform of HKI are both critical for the high rates of glycolysis in gas gland cells. PMID- 27401756 TI - Multiple sensory modalities used by squid in successful predator evasion throughout ontogeny. AB - Squid rely on multiple sensory systems for predator detection. In this study we examine the role of two sensory systems, the lateral line analogue and vision, in successful predator evasion throughout ontogeny. Squid Doryteuthis pealeii and Lolliguncula brevis were recorded using high-speed videography in the presence of natural predators under light and dark conditions with their lateral line analogue intact or ablated via a pharmacological technique. Paralarval squid showed reduced escape responses when ablated; however, no differences were found between light and dark conditions in non-ablated paralarvae, as was previously shown in juveniles and adults, indicating that the lateral line analogue is integral for predator detection early in life. However, vision does play a role in survival because ablated squid in dark conditions had lower levels of survival than all other treatments. Throughout ontogeny, squid oriented themselves anteriorly towards the oncoming predator, maximizing sensory input to the lateral line analogue system and providing better positioning for tail-first escape jetting, the preferred escape mode. Ablated juveniles and adults had lower response times, escape velocities and peak acceleration than non-ablated individuals, indicating that the lateral line analogue enables squid to respond quicker and with more powerful jets to a predator and maximize escape success. Our findings reveal that the lateral line analogue plays a role in predator detection and successful escape response at the earliest life stages, and continues to contribute to successful evasion by aiding visual cues in juvenile and adult squid. PMID- 27401757 TI - Repeatability of locomotor performance and morphology-locomotor performance relationships. AB - There is good evidence that natural selection drives the evolution of locomotor performance, but the processes that generate the among-individual variation for selection to act on are relatively poorly understood. We measured prolonged swimming performance, Ucrit, and morphology in a large cohort (n=461) of wild type zebrafish (Danio rerio) at ~6 months and again at ~9 months. Using mixed model analyses to estimate repeatability as the intraclass correlation coefficient, we determined that Ucrit was significantly repeatable (r=0.55; 95% CI: 0.45-0.64). Performance differences between the sexes (males 12% faster than females) and changes with age (decreasing 0.07% per day) both contributed to variation in Ucrit and, therefore, the repeatability estimate. Accounting for mean differences between sexes within the model decreased the estimate of Ucrit repeatability to 21% below the naive estimate, while fitting age in the models increased the estimate to 14% above the naive estimate. Greater consideration of factors such as age and sex is therefore necessary for the interpretation of performance repeatability in wild populations. Body shape significantly predicted Ucrit in both sexes in both assays, with the morphology-performance relationship significantly repeatable at the population level. However, morphology was more strongly predicative of performance in older fish, suggesting a change in the contribution of morphology relative to other factors such as physiology and behaviour. The morphology-performance relationship changed with age to a greater extent in males than females. PMID- 27401758 TI - Thyroid hormone influences muscle mechanics in carp (Cyprinus carpio) independently from SERCA activity. AB - Thyroid hormone is a key regulator of metabolism, and in zebrafish, hypothyroidism decreases sustained and burst swimming performance. These effects are accompanied by decreases in both metabolic scope and the activity of sarco endoplasmic reticulum ATPase (SERCA) in zebrafish. Our aim was to determine whether thyroid hormone affects skeletal muscle contractile function directly and whether these effects are mediated by influencing SERCA activity. We show that hypothyroidism reduces sustained locomotor performance but not sprint performance in carp (Cyprinus carpio). We accept our hypothesis that hypothyroidism reduces force production in isolated skeletal muscle, when compared with the thyroid hormone T2, but we reject the hypothesis that this effect is mediated by influencing SERCA activity. Blocking SERCA activity with thapsigargin reduced muscle fatigue resistance, but hypothyroidism had no effect on fatigue. Hence, thyroid hormone plays a role in determining isolated skeletal muscle mechanics, but its effects are more likely to be mediated by mechanisms other than affecting SERCA activity. PMID- 27401759 TI - Discrimination of fast click-series produced by tagged Risso's dolphins (Grampus griseus) for echolocation or communication. AB - Early studies that categorized odontocete pulsed sounds had few means of discriminating signals used for biosonar-based foraging from those used for communication. This capability to identify the function of sounds is important for understanding and interpreting behavior; it is also essential for monitoring and mitigating potential disturbance from human activities. Archival tags were placed on free-ranging Grampus griseus to quantify and discriminate between pulsed sounds used for echolocation-based foraging and those used for communication. Two types of rapid click-series pulsed sounds, buzzes and burst pulses, were identified as produced by the tagged dolphins and classified using a Gaussian mixture model based on their duration, association with jerk (i.e. rapid change of acceleration) and temporal association with click trains. Buzzes followed regular echolocation clicks and coincided with a strong jerk signal from accelerometers on the tag. They consisted of series averaging 359+/-210 clicks (mean+/-s.d.) with an increasing repetition rate and relatively low amplitude. Burst pulses consisted of relatively short click series averaging 45+/-54 clicks with decreasing repetition rate and longer inter-click interval that were less likely to be associated with regular echolocation and the jerk signal. These results suggest that the longer, relatively lower amplitude, jerk-associated buzzes are used in this species to capture prey, mostly during the bottom phase of foraging dives, as seen in other odontocetes. In contrast, the shorter, isolated burst pulses that are generally emitted by the dolphins while at or near the surface are used outside of a direct, known foraging context. PMID- 27401760 TI - Neuromuscular effort predicts walk-run transition speed in normal and adapted human gaits. AB - Often, humans and other animals move in a manner that minimizes energy costs. It is more economical to walk at slow speeds, and to run at fast speeds. Here, we asked whether humans select a gait that minimizes neuromuscular effort under novel and unfamiliar conditions, by imposing interlimb asymmetry during split belt treadmill locomotion. The walk-run transition speed changed markedly across different gait conditions: forward, backward, hybrid (one leg forward, one leg backward) and forward with speed differences (one leg faster than the other). Most importantly, we showed that the human walk-run transition speed across conditions was predicted by changes in neuromuscular effort (i.e. summed leg muscle activations). Our results for forward gait and forward gait with speed differences suggest that human locomotor patterns are optimized under both familiar and novel gait conditions by minimizing the motor command for leg muscle activation. PMID- 27401761 TI - Differences in spectral selectivity between stages of visually guided mating approaches in a buprestid beetle. AB - Spectral mating preferences were examined in male Agrilus angustulus (Buprestidae: Coleoptera), a member of a taxon known for its high species diversity and striking metallic coloration. The spectral emission profile of a typical A. angustulus female displays low chroma, broadly overlapping that of the green oak leaves they feed and rest upon, while also including longer wavelengths. To pinpoint behaviorally significant spectral regions for A. angustulus males during mate selection, we observed their field approaches to females of five Agrilus planipennis color morphs that have greater chroma than the normal conspecific female targets. Agrilus angustulus males would initially fly equally frequently toward any of the three longest wavelength morphs (green, copper and red) whose spectral emission profiles all overlap that of typical A. angustulus females. However, they usually only completed approaches toward the two longest wavelength morphs, but not the green morphs. Thus, spectral preference influenced mate selection by A. angustulus males, and their discrimination of suitable targets became greater as these targets were approached. This increasing spectral discrimination when approaching targets may have evolved to allow female emissions to remain somewhat cryptic, while also being visible to conspecifics as distinct from the background vegetation and heterospecific competitors. PMID- 27401762 TI - Effect of temperature on chemosensitive locus coeruleus neurons of savannah monitor lizards, Varanus exanthematicus. AB - Savannah monitor lizards (Varanus exanthematicus) are unusual among ectothermic vertebrates in maintaining arterial pH nearly constant during changes in body temperature in contrast to the typical alpha-stat regulating strategy of most other ectotherms. Given the importance of pH in the control of ventilation, we examined the CO2/H+ sensitivity of neurons from the locus coeruleus (LC) region of monitor lizard brainstems. Whole-cell patch-clamp electrophysiology was used to record membrane voltage in LC neurons in brainstem slices. Artificial cerebral spinal fluid equilibrated with 80% O2, 0.0-10.0% CO2, balance N2, was superfused across brainstem slices. Changes in firing rate of LC neurons were calculated from action potential recordings to quantify the chemosensitive response to hypercapnic acidosis. Our results demonstrate that the LC brainstem region contains neurons that can be excited or inhibited by, and/or are not sensitive to CO2 in V. exanthematicus While few LC neurons were activated by hypercapnic acidosis (15%), a higher proportion of the LC neurons responded by decreasing their firing rate during exposure to high CO2 at 20 degrees C (37%); this chemosensitive response was no longer exhibited when the temperature was increased to 30 degrees C. Further, the proportion of chemosensitive LC neurons changed at 35 degrees C with a reduction in CO2-inhibited (11%) neurons and an increase in CO2-activated (35%) neurons. Expressing a high proportion of inhibited neurons at low temperature may provide insights into mechanisms underlying the temperature-dependent pH-stat regulatory strategy of savannah monitor lizards. PMID- 27401763 TI - It's all in the gills: evaluation of O2 uptake in Pacific hagfish refutes a major respiratory role for the skin. AB - Hagfish skin has been reported as an important site for ammonia excretion and as the major site of systemic oxygen acquisition. However, whether cutaneous O2 uptake is the dominant route of uptake remains under debate; all evidence supporting this hypothesis has been derived using indirect measurements. Here, we used partitioned chambers and direct measurements of oxygen consumption and ammonia excretion to quantify cutaneous and branchial exchanges in Pacific hagfish (Eptatretus stoutii) at rest and following exhaustive exercise. Hagfish primarily relied on the gills for both O2 uptake (81.0%) and ammonia excretion (70.7%). Following exercise, both O2 uptake and ammonia excretion increased, but only across the gill; cutaneous exchange was not increased. When branchial O2 availability was reduced by exposure to anteriorly localized hypoxia (~4.6 kPa O2), cutaneous O2 consumption was only slightly elevated on an absolute basis. These results refute a major role for cutaneous O2 acquisition in the Pacific hagfish. PMID- 27401764 TI - Cardiac reflexes in a warming world: thermal plasticity of barostatic control and autonomic tones in a temperate fish. AB - Thermal plasticity of cardiorespiratory function allows ectotherms like fish to cope with seasonal temperature changes and is critical for resilience to climate change. Yet, the chronic thermal effects on cardiovascular homeostatic reflexes in fish are little understood although this may have important implications for physiological performance and overall resilience to climate warming. We compared cardiac autonomic control and baroreflex regulation of heart rate in perch (Perca fluviatilis L.) from a reference area in the Baltic Sea at 18-19 degrees C with conspecifics from the Biotest enclosure, a chronically heated ecosystem receiving warmed effluent water (24-25 degrees C) from a nuclear power plant. Resting heart rate of Biotest fish displayed clear thermal compensation and was 58.3+/-2.3 beats min-1 compared with 52.4+/-2.6 beats min-1 in reference fish at their respective environmental temperatures (Q10=1.2). The thermally compensated heart rate of Biotest fish was a combined effect of elevated inhibitory cholinergic tone (105% in Biotest fish versus 70% in reference fish) and reduced intrinsic cardiac pacemaker rate. A barostatic response was evident in both groups, as pharmacologically induced increases and decreases in blood pressure resulted in atropine-sensitive bradycardia and tachycardia, respectively. Yet, the tachycardia in Biotest fish was significantly greater, presumably due to the larger scope for vagal release. Acclimation of Biotest fish to 18 degrees C for 3 weeks abolished differences in intrinsic heart rate and autonomic tone, suggesting considerable short-term thermal plasticity of cardiovascular control in this species. The heightened hypotensive tachycardia in Biotest perch may represent an important mechanism of ectothermic vertebrates that safeguards tissue perfusion pressure when tissue oxygen demand is elevated by environmental warming. PMID- 27401765 TI - Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals. AB - Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis. PMID- 27401767 TI - Numerous intertriginous xanthomas in infant: A diagnostic clue for sitosterolemia. AB - Sitosterolemia is a very rare autosomal recessive lipoprotein metabolic disorder caused by homozygous or compound heterozygous mutations in one of the two adenosine triphosphate-binding cassette transporter genes, ABCG5 and ABCG8. Sitosterolemia is clinically characterized by xanthomas and atherosclerosis, arthritis, fever, hemolysis and macrothrombocytopenia even in early childhood. We described a 16-month-old girl, who had numerous yellowish-brown intertriginous xanthomas along the skin creases on the extremities with severe hypercholesterolemia and elevated plant sterol levels. Histopathologically, xanthoma showed aggregation of foam cells in the dermis with a zone of mucin deposits in the dermal papilla. Electron microscopy showed numerous membrane bound lipid droplets and multivesicular lipid bodies in the foam cells, a round cell containing lipid droplets in the basal cell layer and abundant mucin deposits just beneath the basal lamina. Diagnosis of sitosterolemia was confirmed by DNA sequencing showing compound heterozygosity for previously reported missense mutations in exon 9 of ABCG5. Infants presenting with multiple xanthomas should be investigated for sitosterolemia, if there is no family history of dyslipidemia. PMID- 27401766 TI - Adaptive immune response in symptomatic and asymptomatic enteric protozoal infection: evidence for a determining role of parasite genetic heterogeneity in host immunity to human giardiasis. AB - The genetic basis of the ultimate clinical outcomes of human giardiasis has been the subject of numerous investigations. We previously demonstrated roles for both host and parasite factors in determining the outcome of enteric infection in a murine model of Giardia duodenalis infection. In the current study, fecal and serum specimens from healthy controls and human subjects infected with the intestinal parasite G. duodenalis were assessed. Using a semi-nested PCR method, clinical isolates were genetically characterized based on the gdh and tpi loci, and the phylogenetic trees were constructed. Using a sandwich ELISA method, the serum levels of representative TH1 and TH2 cytokines were measured in infected human subjects and healthy controls. Here we showed that symptomatic human giardiasis was characterized by significantly elevated serum levels of the TH1 cytokine IFN-gamma compared to healthy controls, whereas asymptomatic human subjects and healthy controls had comparable levels of serum IFN-gamma. Further analyses showed that human subjects infected with G. duodenalis genotype AI had significantly elevated levels of serum IFN-gamma and IL-10, but not IL-5, whereas human subjects infected with AII had similar levels of those cytokines compared to healthy controls. These data demonstrate roles for both host and parasite factors in the determination of the outcome of enteric infections and may further broaden our understanding of host-parasite interaction during enteric protozoal infections. PMID- 27401768 TI - We need new tools to assess Orthorexia Nervosa. A commentary on "Prevalence of Orthorexia Nervosa among College Students Based on Bratman's Test and Associated Tendencies". PMID- 27401770 TI - Development of a versatile method for targeted gene deletion and insertion by using the pyrF gene in the psychrotrophic bacterium, Shewanella livingstonensis Ac10. AB - Shewanella livingstonensis Ac10, a psychrotrophic bacterium isolated from Antarctic seawater, grows well at low temperatures close to 0 degrees C. The bacterium is useful as a host in a low-temperature protein expression system. It is also useful as a model microorganism to investigate the mechanisms of microbial cold-adaptation. Versatile genetic manipulation techniques would be useful to investigate the biology of this bacterium and to develop its applications. In this study, we developed a method for targeted gene deletion and insertion by using the gene coding for orotidine-5'-phosphate decarboxylase (pyrF), which is involved in pyrimidine synthesis. We found that S. livingstonensis Ac10 is sensitive to 5-fluoroorotic acid (5-FOA), which is converted to a highly toxic compound by the product of pyrF. A uracil-auxotrophic strain resistant to 5-FOA was constructed by deleting pyrF, thus allowing the use of a plasmid-borne copy of pyrF for selection of recombinants. We constructed the pyrF complementation suicide plasmid pKKP, which contains pyrF, the R6K replication origin, the mob site of RP4, an antibiotic marker gene, and a multiple cloning site. To demonstrate pyrF-based gene replacement, we deleted the internal region of orf5, the gene coding for an eicosapentaenoic acid (EPA) synthesis enzyme. We also successfully inserted a His6-tag-coding sequence into orf8, the gene coding for another EPA synthesis enzyme. This system allows the markerless deletion and insertion of desired sequences at specific sites in the genome, which remarkably facilitates genetic manipulation of this bacterium. PMID- 27401769 TI - Exploratory study of the implications of research on the use of smart connected devices for prevention: a scoping review. AB - BACKGROUND: Smart devices and mobile applications are now an integral part of all aspects of everyday life. They are particularly numerous in the field of health, contributing to the movement called ehealth. What is the potential role of these devices as prevention supports? The purpose of this article is to provide an exploratory analysis of the use, efficacy and contribution to conventional prevention strategies. METHODS: To address this issue, we conducted a scoping review on the basis of 105 publications from the fields of medicine and human sciences. RESULTS: Three dimensions of the use of smart devices in the field of health were identified: 1/a quantification tool allowing the users to measure their activities; 2/a tool of self-positioning in the community; 3/an interface between the medical world and the population, modifying the hierarchy of knowledge. However, few published studies have investigated the determinants of the efficacy of these devices and their impact on individual behaviours and professional health practices. CONCLUSION: Based on the hypothesis of possible integration of these devices in prevention policies, it would be interesting to investigate two research issues: how and under what psycho-socio-environmental conditions can smart devices contribute to the adoption of positive health behaviours? To what degree does the use of smart devices modify the health care professional-patient relationship? Finding answers to these questions could help to define the real place of these devices in prevention strategies by determining their complementarity with respect to other prevention strategies, and the conditions of their efficacy on behaviours and inequalities. PMID- 27401771 TI - How large are the consequences of covariate imbalance in cluster randomized trials: a simulation study with a continuous outcome and a binary covariate at the cluster level. AB - BACKGROUND: The number of clusters in a cluster randomized trial is often low. It is therefore likely random assignment of clusters to treatment conditions results in covariate imbalance. There are no studies that quantify the consequences of covariate imbalance in cluster randomized trials on parameter and standard error bias and on power to detect treatment effects. METHODS: The consequences of covariance imbalance in unadjusted and adjusted linear mixed models are investigated by means of a simulation study. The factors in this study are the degree of imbalance, the covariate effect size, the cluster size and the intraclass correlation coefficient. The covariate is binary and measured at the cluster level; the outcome is continuous and measured at the individual level. RESULTS: The results show covariate imbalance results in negligible parameter bias and small standard error bias in adjusted linear mixed models. Ignoring the possibility of covariate imbalance while calculating the sample size at the cluster level may result in a loss in power of at most 25 % in the adjusted linear mixed model. The results are more severe for the unadjusted linear mixed model: parameter biases up to 100 % and standard error biases up to 200 % may be observed. Power levels based on the unadjusted linear mixed model are often too low. The consequences are most severe for large clusters and/or small intraclass correlation coefficients since then the required number of clusters to achieve a desired power level is smallest. CONCLUSIONS: The possibility of covariate imbalance should be taken into account while calculating the sample size of a cluster randomized trial. Otherwise more sophisticated methods to randomize clusters to treatments should be used, such as stratification or balance algorithms. All relevant covariates should be carefully identified, be actually measured and included in the statistical model to avoid severe levels of parameter and standard error bias and insufficient power levels. PMID- 27401772 TI - Mini-Invasive floating metatarsal osteotomy for resistant or recurrent neuropathic plantar metatarsal head ulcers. AB - BACKGROUND: Patients with peripheral neuropathy and pressure under a relatively plantar deviated metatarsal head frequently develop plantar foot ulcers. When conservative management with orthotics and shoes does not cure the ulcer, surgical metatarsal osteotomy may be indicated to relieve the pressure and enable the ulcer to heal. The purpose of this study is to evaluate the use of a mini invasive floating metatarsal osteotomy in treating recalcitrant ulcers or recurrent ulcers plantar to the metatarsal heads in patients with diabetes mellitus (DM) related neuropathy. METHODS: Computerized medical files of patients with diabetic neuropathy treated with an osteotomy during 2013 and 2014 were retrospectively reviewed. There were 20 osteotomies performed on 17 patients (mean age 58 years). The patients had a diagnosis of DM for a mean of 17 years. All ulcers were University of Texas grade 1A; mean ulcer age was 19 months. RESULTS: After 17/20 operations, the ulcer completely resolved after 6 weeks and did not recur after a mean follow-up of 11.5 months. One patient developed an early post-operative infection with osteomyelitis at the osteotomy site (proximal shaft of the fifth metatarsal) that needed debridement and IV antibiotics. In the other 19 cases, the surgical wound healed within 1 week. Asymptomatic radiological non-union developed in six cases (30 %). CONCLUSIONS: Mini-invasive floating metatarsal osteotomy can cure resistant and recurrent University of Texas grade 1A ulcerations plantar to the metatarsal heads in neuropathic patients. PMID- 27401773 TI - Match between culture and social support: Acculturation moderates the relationship between social support and well-being of Chinese American breast cancer survivors. AB - PURPOSE: Social support does not always lead to health benefits; the outcomes depend on the match between the need and the provision of social support. Culture shapes individuals' preference of social support types (e.g., supportive communication, social companionship, and tangible support). The present study examined how the association between social support and well-being may vary as a function of acculturation among minority cancer survivors. METHODS: One hundred and twenty-three Chinese American breast cancer survivors were invited to complete a questionnaire package. RESULTS: Findings showed that acculturation moderated the association of social support subtypes with psychological and physical well-being. Higher emotional/information support was associated with better quality of life and less physical symptoms among highly acculturated cancer survivors but more physical symptoms among those who were less acculturated. Tangible support was associated with more physical symptoms among highly acculturated cancer survivors but less physical symptoms among those who are less acculturated. Positive social interaction was associated with better quality of life and less physical symptoms among less acculturated cancer survivors but not associated with quality of life or physical symptoms among their highly acculturated counterparts. CONCLUSION: The findings pointed to the significance of acculturation in breast cancer experience among minority women, especially its interplay with social support transactions. PMID- 27401775 TI - A potential relationship between skin hydration and stamp-type microneedle intradermal hyaluronic acid injection in middle-aged male face. AB - There is an increasing interest in skin rejuvenation using hyaluronic acid (HA) fillers beyond the improvement of deep wrinkles and volume deficiencies, which have been primary research foci in the past. We conducted a pilot study using a sample of six middle-aged male subjects. Using an automatic intradermal injector with 0.020 mL of material contained in each injection point with a total of 100 points, 2 mL of non-cross-HA filler was injected into the entire face at every treatment session. We administered injections of HA for a total of three sessions per subject at 2-week intervals and evaluated the results using a corneometer, TEWL, cutometer, measures of patient satisfaction, and the global aesthetic improvement scale (GAIS). Corneometer values increased steadily at each measurement, while the average value of TEWL increased in comparison with baseline after each application of the procedure. However, values returned to readings similar to those at 4 weeks after complete termination of the procedures. Cutometer values differed between the baseline and after procedures. All patients were assessed as "very much improved" or "much improved" according to GAIS, and all were pleased with the outcomes of treatment in terms of the enhancement of moisture, elasticity, and brightness. PMID- 27401776 TI - New aspect for systemic effects of COPD: eye findings. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) has multisystemic implications and comorbidities. Hypoxia and systemic inflammation are thought to involve oculary structures. In this study, our aim is to evaluate retinal nerve fiber and choroidal thickness and retinal vessel diameter using the spectral domain optical coherence tomography (SD-OCT) in COPD subjects. METHODS: Forty three subjects diagnosed with COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria at the Pulmonology Department of Pamukkale University were enrolled in the study. All subjects underwent respiratory function testing and a carbon monoxide diffusion test. To determine hypoxic state, arterial blood gas analysis was performed. The control group consisted of 31 subjects with comparable age and gender distribution. All participants underwent a standard ophthalmic examination including visual acuity assessment, biomicroscopy, air-puff tonometry, indirect retinoscopy, and SD-OCT measurements. RESULTS: The mean subfoveal choroidal thickness (SFCT), foveal thickness, and retinal arteriolar caliber were found to be similar in both groups, while the mean retinal venular caliber value was markedly higher in the COPD group. The mean peripapillary retinal nerve fiber layer (RNFL) thickness was 100.2+/-11.8 um in the COPD group and 105.6 +/- 8.1 um in the control group (P = .03). The inferior quadrant RNFL was significantly thinner in the COPD group. CONCLUSIONS: The results of this study showed increasing diameter of the retinal veins, thinning of the RNFL, and SFCT may be associated to chronic inflammation and hypoxia in subjects with COPD. Future guidelines may include ocular findings to the present systemic manifestations of COPD. PMID- 27401777 TI - Mycotoxin contamination in laboratory rat feeds and their implications in animal research. AB - Compound feed is particularly vulnerable to multi-mycotoxin contamination. A method for the determination of 12 mycotoxins; enniatins A, A1, B, B1; aflatoxins B1, B2, G1, G2; OTA; ZEA; T-2 and HT-2 by liquid chromatography-tandem mass spectrometry has been developed and applied for the analysis of laboratory rat commercial feeds. The method trueness was checked by recovery assays at three different spiked levels (n = 9). Recoveries ranged from 73% to 112%, and the intra-day and inter-day precision were lower than 9% and 13%, respectively. Limits of quantitation were lower than 15 MUg/kg. Twenty-seven laboratory rats feed samples showed multi-contamination by at least three up to six different mycotoxins. ENNs B and B1, followed by ZEA were the most prevalent mycotoxins. T 2, HT-2, and OTA were not detected. ZEA showed the highest concentration levels reaching 492 MUg/kg. The results underline the importance of implementing mycotoxin regular surveillance programs for laboratory animal feeds. PMID- 27401778 TI - Statement of Retraction. PMID- 27401779 TI - Treatment of Progressive Multifocal Leukoencephalopathy With Mirtazapine. AB - BACKGROUND AND OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a rare, JC-virus-mediated, demyelinating disease with a high mortality rate. As no recommended treatment exists, mirtazapine, a potential blocker of virus entry into cells, has been empirically used. METHODS: We analysed existing data on mirtazapine's efficacy to treat PML by systematically reviewing the literature since 2005, when it was first used. RESULTS: Searches in PubMed, EBSCO, SCOPUS and Google Scholar between January 2005 and December 2015, identified five cohort studies and 74 case reports. No statistically significant effect of mirtazapine on PML outcome was observed in the cohort studies. From studying the case reports, mortality rate for PML was associated with the underlying circumstances, such as an older age, the use of an immunosuppressant, or PML occurring in patients with a haematological malignancy or a transplant. CONCLUSIONS: Except for natalizumab-associated PML, we did not highlight any potential benefit of mirtazapine on disease outcomes. Further interventional studies are needed to confirm that 5-HT2AR inhibition is relevant to treat PML. PMID- 27401780 TI - Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis. AB - BACKGROUND AND OBJECTIVES: The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. METHODS: Our case series involved 27 patients [mean age 70 +/- 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age >=75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 +/- 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 +/- 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. RESULTS: The mean left ventricular ejection fraction was 48 +/- 9 %, the left atrial diameter was 46.5 +/- 7 mm, and the estimated glomerular filtration rate was 45 +/- 21 mL/min/1.73 m(2). The mean duration of treatment was 15 +/- 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. CONCLUSIONS: Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications. PMID- 27401781 TI - Molecular Assessment of Microcirculation Injury in Formalin-Fixed Human Cardiac Allograft Biopsies With Antibody-Mediated Rejection. AB - Precise diagnosis of antibody-mediated rejection (AMR) in cardiac allograft endomyocardial biopsies (EMBs) remains challenging. This study assessed molecular diagnostics in human EMBs with AMR. A set of 34 endothelial, natural killer cell and inflammatory genes was quantified in 106 formalin-fixed, paraffin-embedded EMBs classified according to 2013 International Society for Heart and Lung Transplantation (ISHLT) criteria. The gene set expression was compared between ISHLT diagnoses and correlated with donor-specific antibody (DSA), endothelial injury by electron microscopy (EM) and prognosis. Findings were validated in an independent set of 57 EMBs. In the training set (n = 106), AMR cases (n = 70) showed higher gene set expression than acute cellular rejection (ACR; n = 21, p < 0.001) and controls (n = 15, p < 0.0001). Anti-HLA DSA positivity was associated with higher gene set expression (p = 0.01). Endothelial injury by electron microscopy strongly correlated with gene set expression, specifically in AMR cases (r = 0.62, p = 0.002). Receiver operating characteristic curve analysis for diagnosing AMR showed greater accuracy with gene set expression (area under the curve [AUC] = 79.88) than with DSA (AUC = 70.47) and C4d (AUC = 70.71). In AMR patients (n = 17) with sequential biopsies, increasing gene set expression was associated with inferior prognosis (p = 0.034). These findings were confirmed in the validation set. In conclusion, biopsy-based molecular assessment of antibody mediated microcirculation injury has the potential to improve diagnosis of AMR in human cardiac transplants. PMID- 27401782 TI - Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study. AB - OBJECTIVE: Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. METHODS: Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. RESULTS: 269 patients with PD-MCI (age 67.8+/-7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2+/ 11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. CONCLUSIONS: This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia. PMID- 27401783 TI - Second line therapies in polycythemia vera: What is the optimal strategy after hydroxyurea failure? AB - Cytoreductive therapies have traditionally been the standard treatment for older patients with polycythemia vera (PV) or those with a history of prior thrombosis. Hydroxyurea (HU) is the most frequently used cytoreductive agent in PV. However, approximately 24% of patients treated with HU will eventually develop resistance or intolerance and patients who fail HU have an increased risk of death, transformation to myelofibrosis or acute myeloid leukemia. Interferon-alpha has been used in younger PV patients and is capable of inducing a complete hematologic response and significant reductions, or even eradication, of JAK2 V617F mutation allele burdens in a small but notable subset of PV patients. The potential toxicities of interferon-alpha must be weighed against the disease control benefit in a case-by-case fashion. Recently JAK2 inhibitor, ruxolitinib, demonstrated significant improvement in controlling the hematocrit and splenomegaly versus best available therapy in patients with PV who failed or are intolerant to HU and currently is FDA-approved in this setting. In this review, we will discuss novel emerging therapies for PV with a special focus on the currently available and upcoming treatment options for patients who fail HU. PMID- 27401784 TI - Characterization of proteolytic and anti-proteolytic activity involvement in sterlet spermatozoon maturation. AB - In sturgeon, the acquisition of the potential for motility activation called spermatozoon maturation takes place outside testes. This process can be accomplished in vitro by pre-incubation of immature testicular spermatozoa in seminal fluid collected from fully mature Wolffian duct sperm. Addition of trypsin inhibitor to the pre-incubation medium disrupts spermatozoon maturation. There are no available data for the role of proteolysis regulators in fish spermatozoon maturation, while their role is recognized in mammalian sperm maturation. The present study evaluated the involvement of seminal fluid proteases and anti-proteolytic activity in the sterlet spermatozoon maturation process. Casein and gelatin zymography and quantification of amidase and anti proteolytic activity were conducted in sturgeon seminal fluid from Wolffian duct sperm and seminal fluid from testicular sperm, along with spermatozoon extracts from Wolffian duct spermatozoa, testicular spermatozoa, and testicular spermatozoa after in vitro maturation. We did not find significant differences in proteolytic profiles of seminal fluids from Wolffian duct sperm and ones from testicular sperm. Zymography revealed differences in spermatozoon extracts: Wolffian duct spermatozoon extracts were characterized by the presence of a broad proteolytic band ranging from 48 to 41 kDa, while testicular spermatozoon extracts did not show such activity until after in vitro maturation. The differences in amidase activity coincided with these results. It may not be the levels of proteolytic and anti-proteolytic activity per se, but the alterations in their interactions triggering a cascade of signaling events, that is crucial to the maturation process. PMID- 27401785 TI - Expression, purification and biological activity assessment of romiplostim biosimilar peptibody. AB - BACKGROUND: Romiplostim is a peptibody analogue of thrombopoietin (TPO) which regulates platelet production. This molecule consists of two main parts: Peptide sequences which like wild type TPO, mimics stimulation of TPO receptor and IgG1Fc, (Peptide + Antibody = Peptibody). This drug is used in treatment of chronic Immune Thrombocytopenic Purpura (ITP). METHODS: In this project E. coli bacteria were transformed by a construct harboring peptibody fusion gene. This construct consisted of two repeated peptide sequences which have fused to Carboxyl group of IgG1Fc. Designed construct in E. coli host resulted in protein expression in cytoplasm as inclusion body. The inclusion bodies were separated, washed and after denaturation and solubilization, in the last stage the desired peptibodies were refolded and purified. The resulting peptibodies were characterized by SDS-PAGE and Western immunoblotting. The bioactivity were assessed in vivo using subcutaneous injection in mice. RESULTS: Results showed accurate molecules were produced and purified. Also, in vivo experiment showed significant increment (more than two fold) of platelets compared to control group. CONCLUSION: In this study laboratory scale production of recombinant romiplostim showed proper in-vivo bioactivity. This new approach in expression and purification of this recently introduced thrombopoietin receptor agonist drug may be followed by scale up of its production to response the chronic ITP patient's demand. PMID- 27401786 TI - Developing a successful treatment for co-morbid insomnia and sleep apnoea. AB - Insomnia and sleep apnoea are the two most common sleep disorders, found in 6% and 23-50% of the general population respectively. These disorders also frequently co-occur, with 39-58% of sleep apnoea patients reporting symptoms indicative of co-morbid insomnia. When these disorders co-occur, clinicians are faced with difficult treatment decisions, patients experience the additive detrimental impacts of both disorders, and the effectiveness of discrete treatments for each disorder may be impaired. A common finding is that co-morbid insomnia and sleep apnoea (COMISA) is more difficult to treat than either disorder presenting alone. Co-morbid insomnia reduces the initial acceptance of, and later adherence to, continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea. This has resulted in recent recommendations that treatment approaches should initially target COMISA patients' insomnia to remove this barrier to CPAP treatment, and improve patient outcomes. However, no randomised controlled trial outcomes investigating this treatment approach currently exist. The current article aims to review and integrate recent research examining the prevalence, characteristics, and theoretical mechanistic relationships between co-occurring insomnia and OSA, and discuss previous treatment attempts. PMID- 27401787 TI - Effect of oral administration of Tribulus terrestris extract on semen quality and body fat index of infertile men. AB - Male fertility can be evaluated through complete semen analysis. Plants belonging to the Tribulus genus are known for their role in enhancing sex hormone levels and semen quality. The aim of this study was to evaluate the effects of T. terrestris on semen quality and physiological parameters. Sixty-five men with abnormal semen evaluation were included in this study, in which they were prescribed with oral administration of Androsten(r) (250 mg of Tribulus terrestris dried extract per capsule). Body fat percentage, lean muscle mass gain, fluctuation in steroid hormone levels and all semen parameters were analysed during the period of treatment. The results demonstrated that decrease in the percentage of body fat and increase in lean mass were significant, as well as increase in dihydrotestosterone levels. Complete semen analysis evaluated at the end of treatment showed significant enhancement in sperm concentration, motility and liquefaction time. Protodioscin, the main phytochemical agent of the Tribulus genus, acts on sertoli cells, germ cell proliferation and growth of seminiferous tubules. This component is known to convert testosterone into dihydrotestosterone, which plays important roles in male attributes. Our results indicate the therapeutic use of Tribulus terrestris by men presenting altered semen parameters, and/or undergoing infertility treatment. PMID- 27401789 TI - Erratum to Hymenobacter arcticus sp. nov., isolated from glacial till. PMID- 27401788 TI - Cilostazol Enhances Mobilization of Circulating Endothelial Progenitor Cells and Improves Endothelium-Dependent Function in Patients at High Risk of Cardiovascular Disease. AB - This is the first study to investigate the vasculoangiogenic effects of cilostazol on endothelial progenitor cells (EPCs) and flow-mediated dilatation (FMD) in patients at high risk of cardiovascular disease (CVD). This double blind, placebo-controlled study included 71 patients (37 received 200 mg/d cilostazol and 34 received placebo for 12 weeks). Use of cilostazol, but not placebo, significantly increased circulating EPC (kinase insert domain receptor(+)CD34(+)) counts (percentage changes: 149.0% [67.9%-497.8%] vs 71.9% [ 31.8% to 236.5%], P = .024) and improved triglyceride and high-density lipoprotein cholesterol levels (P = .002 and P = .003, respectively). Plasma levels of vascular endothelial growth factor (VEGF)-A165 and FMD significantly increased (72.5% [32.9%-120.4%] vs -5.8% [-46.0% to 57.6%], P = .001; 232.8% +/- 83.1% vs -46.9% +/- 21.5%, P = .003, respectively) in cilostazol-treated patients. Changes in the plasma triglyceride levels significantly inversely correlated with the changes in the VEGF-A165 levels and FMD. Cilostazol significantly enhanced the mobilization of EPCs and improved endothelium dependent function by modifying some metabolic and angiogenic markers in patients at high risk of CVD. PMID- 27401790 TI - N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related DeltaFosB alterations. AB - Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is DeltaFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N acetylcysteine, a l-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for DeltaFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol induced behavioural sensitization, the increase of DeltaFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders. PMID- 27401791 TI - How to diagnose NAFLD in 2016. PMID- 27401792 TI - Implications of non-coding RNAs in viral infections. AB - The advances in RNA sequencing have unveiled various non-coding RNAs (ncRNAs), which modulate the gene expression. ncRNAs do not get translated into proteins. These include transfer RNAs, ribosomal RNAs, microRNA (miRNA), short interfering RNA, long non-coding RNA, piwi-interacting RNA and small nuclear RNA. ncRNAs regulate gene expression at various levels and control cellular machinery. miRNAs have been reported in plants, animals, several invertebrates and viruses. The miRNAs regulate the gene expression post-transcriptionally. Viral infection strongly influences the abundance and the distribution of miRNAs and other ncRNAs within the host cells. Viruses may encode their own miRNA, which help in the viral life cycle and other aspects of pathogenesis. Viruses are known to successfully modulate the expression pattern of ncRNAs. The ncRNA-based strategies adopted by viruses for their survival present a complex picture of host-virus interactions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401793 TI - A cognitive fMRI study in non-manifesting LRRK2 and GBA carriers. AB - Mutations in the GBA and LRRK2 genes account for one-third of the prevalence of Parkinson's disease (PD) in Ashkenazi Jews. Non-manifesting carriers (NMC) of these mutations represent a population at risk for future development of PD. PD patient who carry mutations in the GBA gene demonstrates more significant cognitive decline compared to idiopathic PD patients. We assessed cognitive domains using fMRI among NMC of both LRRK2 and GBA mutations to better understand pre-motor cognitive functions in these populations. Twenty-one LRRK2-NMC, 10 GBA NMC, and 22 non-manifesting non-carriers (NMNC) who participated in this study were evaluated using the standard questionnaires and scanned while performing two separate cognitive tasks; a Stroop interference task and an N-Back working memory task. Cerebral activation patterns were assessed using both whole brain and predefined region of interest (ROI) analysis. Subjects were well matched in all demographic and clinical characteristics. On the Stroop task, in spite of similar behavior, GBA-NMC demonstrated increased task-related activity in the right medial frontal gyrus and reduced task-related activity in the left lingual gyrus compared to both LRRK2-NMC and NMNC. In addition, GBA-NMC had higher activation patterns in the incongruent task compared to NMNC in the left medial frontal gyrus and bilateral precentral gyrus. No whole-brain differences were noted between groups on the N-Back task. Paired cognitive and task-related performance between GBA-NMC, LRRK2-NMC, and NMNC could indicate that the higher activation patterns in the incongruent Stroop condition among GBA-NMC compared to LRRK2-NMC and NMNC may represent a compensatory mechanism that enables adequate cognitive performance. PMID- 27401794 TI - Bowel in Chest: Type IV Hiatal Hernia. PMID- 27401797 TI - Lorlatinib Is Active in Drug-Resistant NSCLC. AB - Data from a phase I study indicate that the investigational ALK inhibitor lorlatinib is active in patients with ALK- or ROS1-positive non-small cell lung cancer, including those with brain metastases. Objective responses were seen among patients with known ALK resistance mutations who had relapsed following treatment with other tyrosine kinase inhibitors. PMID- 27401800 TI - Systematic literature review of treatments for management of complications of ischemic central retinal vein occlusion. AB - BACKGROUND: To understand the clinical and economic outcomes of treatments for managing complications of ischemic central retinal vein occlusion (iCRVO). METHODS: We conducted a systematic literature review by searching multiple databases and ophthalmology conferences from 2004 to 2015. Studies published in English language and populations of age >=45 years were included. For clinical endpoints, we defined eligibility criteria as randomized controlled trials, prospective before-and-after study designs, and non-randomized studies reporting on treatments in patients with iCRVO. For economic endpoints, all types of study design except cost-of-illness studies were included. We evaluated the definitions of ischemia, clinical and economic endpoints, and rate of development of complications. Risk of bias was assessed for clinical studies using the Cochrane risk-of-bias tool. RESULTS: A total of 20 studies (1338 patients) were included. Treatments included anti-vascular endothelial growth factors (anti-VEGFs), steroids, and procedures primarily targeting macular edema and neovascularization. Ischemia was not defined consistently in the included studies. The level of evidence was mostly low. Most treatments did not improve visual acuity significantly. Development of treatment complications ranged from 11 to 57 %. Incremental cost-effectiveness ratios reported for anti-VEGFs and steroids were below the accepted threshold of GBL30,000, but considering such treatments only ameliorate disease symptoms they seem relatively expensive. CONCLUSIONS: There is a lack of evidence for any intervention being effective in iCRVO, especially in the prevention of neovascularisation. iCRVO poses a significant clinical and economic burden. There is a need to standardize the definition of ischemia, and for innovative treatments which can significantly improve visual outcomes and prevent neovascular complications. PMID- 27401802 TI - Backscattering of linearly polarized light from turbid tissue-like scattering medium with rough surface. AB - In the framework of further development of a unified computational tool for the needs of biomedical optics, we introduce an electric field Monte Carlo (MC) model for simulation of backscattering of coherent linearly polarized light from a turbid tissue-like scattering medium with a rough surface. We consider the laser speckle patterns formation and the role of surface roughness in the depolarization of linearly polarized light backscattered from the medium. The mutual phase shifts due to the photons' pathlength difference within the medium and due to reflection/refraction on the rough surface of the medium are taken into account. The validation of the model includes the creation of the phantoms of various roughness and optical properties, measurements of co- and cross polarized components of the backscattered/reflected light, its analysis and extensive computer modeling accelerated by parallel computing on the NVIDIA graphics processing units using compute unified device architecture (CUDA). The analysis of the spatial intensity distribution is based on second-order statistics that shows a strong correlation with the surface roughness, both with the results of modeling and experiment. The results of modeling show a good agreement with the results of experimental measurements on phantoms mimicking human skin. The developed MC approach can be used for the direct simulation of light scattered by the turbid scattering medium with various roughness of the surface. PMID- 27401801 TI - The effects of respiratory sinus arrhythmia on anger reactivity and persistence in major depression. AB - The experience of anger during a depressive episode has recently been identified as a poor prognostic indicator of illness course. Given the clinical implications of anger in major depressive disorder (MDD), understanding the mechanisms involved in anger reactivity and persistence is critical for improved intervention. Biological processes involved in emotion regulation during stress, such as respiratory sinus arrhythmia (RSA), may play a role in maintaining negative moods. Clinically depressed (MDD; n = 49) and nondepressed (non-MDD; n = 50) individuals were challenged with a stressful computer task shown to increase anger, while RSA (high frequency range 0.15-0.4 Hz) was collected. RSA predicted future anger, but was unrelated to current anger. That is, across participants, low baseline RSA predicted anger reactivity during the task, and in depressed individuals, those with low RSA during the task had a greater likelihood of anger persistence during a recovery period. These results suggest that low RSA may be a psychophysiological process involved in anger regulation in depression. Low RSA may contribute to sustained illness course by diminishing the repair of angry moods. PMID- 27401803 TI - Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke. AB - Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals. PMID- 27401804 TI - Sustained diffusion reversal with in-bore reperfusion in monkey stroke models: Confirmed by prospective magnetic resonance imaging. AB - Although early diffusion lesion reversal after recanalization treatment of acute ischaemic stroke has been observed in clinical settings, the reversibility of lesions observed by diffusion-weighted imaging remains controversial. Here, we present consistent observations of sustained diffusion lesion reversal after transient middle cerebral artery occlusion in a monkey stroke model. Seven rhesus macaques were subjected to endovascular transient middle cerebral artery occlusion with in-bore reperfusion confirmed by repeated prospective diffusion weighted imaging. Early diffusion lesion reversal was defined as lesion reversal at 3 h after reperfusion. Sustained diffusion lesion reversal was defined as the difference between the ADC-derived pre-reperfusion maximal ischemic lesion volume (ADCD-P Match) and the lesion on 4-week follow-up FLAIR magnetic resonance imaging. Diffusion lesions were spatiotemporally assessed using a 3-D voxel-based quantitative technique. The ADCD-P Match was 9.7 +/- 6.0% (mean +/- SD) and the final infarct was 1.2-6.0% of the volume of the ipsilateral hemisphere. Early diffusion lesion reversal and sustained diffusion lesion reversal were observed in all seven animals, and the calculated percentages compared with their ADCD-P Match ranged from 8.3 to 51.9% (mean +/- SD, 26.9 +/- 15.3%) and 41.7-77.8% (mean +/- SD, 65.4 +/- 12.2%), respectively. Substantial sustained diffusion lesion reversal and early reversal were observed in all animals in this monkey model of transient focal cerebral ischaemia. PMID- 27401805 TI - Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner. AB - Positron emission tomography (PET) with 15O-tracers is commonly used to measure brain hemodynamic parameters such as cerebral blood flow, cerebral blood volume, and cerebral metabolic rate of oxygen. Conventionally, the absolute quantification of these parameters requires an arterial input function that is obtained invasively by sampling blood from an artery. In this work, we developed and validated an image-derived arterial input function technique that avoids the unreliable and burdensome arterial sampling procedure for full quantitative 15O PET imaging. We then compared hemodynamic PET imaging performed on a PET/MR hybrid scanner against a conventional PET only scanner. We demonstrated the proposed imaging-based technique was able to generate brain hemodynamic parameter measurements in strong agreement with the traditional arterial sampling based approach. We also demonstrated that quantitative 15O-PET imaging can be successfully implemented on a PET/MR hybrid scanner. PMID- 27401806 TI - Cerebral blood flow MRI in the nondemented elderly is not predictive of post operative delirium but is correlated with cognitive performance. AB - Three-dimensional Arterial Spin Labeling (ASL) MRI was performed before surgery in a cohort of 146 prospectively enrolled subjects >= 70 years old scheduled to undergo elective surgery. We investigated the prospective association between ASL derived measures of cerebral blood flow (CBF) before surgery with postoperative delirium incidence and severity using whole-brain and globally normalized voxel wise analysis. We also investigated the cross-sectional association of CBF with patients' baseline performance on specific neuropsychological tests, and with a composite general cognitive performance measure (GCP). Out of 146 subjects, 32 (22%) developed delirium. We found no significant association between global and voxel-wise CBF with delirium incidence or severity. We found the most significant positive associations between CBF of the posterior cingulate and precuneus and the Hopkins Verbal Learning Test - Revised total score, Visual Search and Attention Test (VSAT) score and the GCP composite. VSAT score was also strongly associated with right parietal lobe CBF. ASL can be employed in a large, well characterized older cohort to examine associations between CBF and age-related cognitive performance. Although ASL CBF measures in regions previously associated with preclinical Alzheimer's Disease were correlated with cognition, they were not found to be indicators of baseline pathology that may increase risk for delirium. PMID- 27401808 TI - Hypersexuality induced by rasagiline in monotherapy in Parkinson's disease. PMID- 27401807 TI - Vagus nerve stimulation in drug-resistant epilepsy: the efficacy and adverse effects in a 5-year follow-up study in Iran. AB - Drug-resistant epilepsy seems like a different disease compared with easy to control epilepsy, and new strategies are needed to help these patients. Vagus nerve stimulation (VNS) therapy is the most frequently used neurostimulation modality for patients with drug-resistant epilepsy who are not eligible for seizure surgery. In this study, we aimed to evaluate the efficacy and adverse effects of VNS in patients with drug-resistant epilepsy in an open-label, prospective, long-term study in Iran. We selected 48 patients with partial-onset drug-resistant epilepsy. Implantations were performed in the neurosurgery department of Loghman Hospital, Tehran, Iran. Follow-up visits were done on monthly bases for 5 years. Forty-four patients completed the study. Mean age of patients was 24.4 years. Mean years of epilepsy history was 14 years. The mean number of anti-epileptic drugs did not significantly change over five years (p = 0.15). There was no exacerbation of epilepsy; however, one patient discontinued his therapy due to unsatisfactory results. Five patient had more than 50 %, and 26 patients (59 %) had 25-49 % reduction in the frequency of monthly seizures persistently. Overall mean frequency of monthly seizures decreased by 57.8, 59.6, 65, 65.9, and 67 %, in 1st, 2nd, 3rd, 4th, and 5th years of follow-up, respectively. Most common side effects were as follows: hoarseness (25 %) and throat discomfort (10 %). We found VNS as a safe and effective therapy for drug resistant epilepsy, with an approximate long-term decrease in mean seizure frequency of 57.8-67 %. Thus, VNS is recommended for suitable patients in developing countries. PMID- 27401809 TI - The reproducibility issue and preclinical academic drug discovery: educational and institutional initiatives fostering translation success. AB - INTRODUCTION: Drug discovery depends critically upon published results from the academy. The reproducibility of preclinical research findings reported by academia in the peer-reviewed literature has been called into question, seriously jeopardizing the value of academic science for inventing therapeutics. AREAS COVERED: The corrosive effects of the reproducibility issue on drug discovery are considered. Purported correctives imposed upon academia from the outside deal mainly with expunging fraudulent literature and imposing punitive sanctions on the responsible authors. The salutary influence of such post facto actions on the reproducibility of discovery-relevant preclinical research data from academia appears limited. Rather, intentional doctoral-scientist education focused on data replicability and translationally-meaningful science and active participation of university entities charged with research innovation and asset commercialization toward ensuring data quality are advocated as key academic initiatives for addressing the reproducibility issue. EXPERT OPINION: A mindset shift on the part of both senior university faculty and the academy to take responsibility for the data reproducibility crisis and commit proactively to positive educational, incentivization, and risk- and reward-sharing practices will be fundamental for improving the value of published preclinical academic research to drug discovery. PMID- 27401810 TI - The Investigation of Cortical Auditory Evoked Potentials Responses in Young Adults Having Musical Education. PMID- 27401811 TI - Matrix solid-phase dispersion combined to liquid chromatography-tandem mass spectrometry for the determination of paraben preservatives in mollusks. AB - A method for the extraction and determination of seven parabens, esters of 4 hydroxybenzoic acid, widely used as preservatives in personal care products, pharmaceuticals, etc., and two chlorinated derivatives (mono- and di-chloro methyl paraben) from mollusk samples was developed by combining matrix solid phase dispersion (MSPD) and liquid chromatography-tandem mass spectrometry. MSPD parameters, such as solvent, solid support and clean-up sorbent, were optimized. Besides, since blank problems were observed for some parabens, these were investigated and blanks were tackled by precleaning all sorbents prior to use. Under final conditions, 0.5g of freeze-dried mollusk were dispersed with 1.2g of silica and packed into a cartridge containing 3g of C18, as on-line clean-up sorbent. This cartridge was eluted with 10mL of acetonitrile, evaporated and reconstituted in methanol for analysis. In the validation stage, successful linearity (R(2)>0.999), recoveries (between 71 and 117% for most analytes), precision (RSD lower than 21%) and limits of detection and quantification (LOD and LOQ, lower than 0.4 and 1.4ngg(-1) dry weight respectively) levels were achieved. Finally, the new methodology was applied to mussel, clam and cockle samples. Methyl paraben was above the LOQ in five of the six samples (not found in one clam sample) at concentrations up to 7ngg(-1) dry weight. Ethyl paraben was found above the LOQ in mussel and cockle samples at a concentration level around 0.3ngg(-1). n-Propyl paraben was only above the LOQ in one mussel sample. PMID- 27401812 TI - Simultaneous determination of polycyclic aromatic hydrocarbon quinones by gas chromatography-tandem mass spectrometry, following a one-pot reductive trimethylsilyl derivatization. AB - We developed a sensitive and selective method to simultaneously analyze 37 polycyclic aromatic hydrocarbon quinones (PAHQs) with GC-MS/MS and applied the method to the analysis of standard atmospheric particulate matter samples. PAHQs were reduced with zinc granules and dithiothreitol (DTT) and the reductants were immediately converted to their silylated derivatives in a test tube. Two trimethylsilyl (TMS) groups were introduced into PAHQs through the one-pot reductive TMS derivatization. The PAHQs were derivatized with a mixed silylation reagent (BSA+TMCS+TMSI; (3:2:3)), which is one of the combinations of TMS derivatization reagents with the highest reactivity. The derivatives produced different fragmentation between o-PAHQs and p-PAHQs. Therefore, isomers that have the same molecular weight are difficult to separate on a column were separated by the selected reaction monitoring (SRM) mode using the characteristic fragmentations, allowing separation and detection of all PAHQ derivatives in less than 30min. The instrumental detection limit (IDL) of each PAHQ was 1.2 29fg/injection and the method quantification limit (MQL) was 0.8-78MUg/kg sample. For quantification, six deuterated PAHQs were used as internal standards to achieve high analytical precision. We applied the developed method to four standard atmospheric particulate matter samples. Results showed that out of 37 PAHQs, 33 compounds were identified and quantified. Moreover, from the 33 PAHQs, 14 were detected for the first time. Similar values were observed for the concentrations of PAHQs that have been quantified in previous reports. This method has the highest practicality in monitoring PAHQs in atmosphere, combustion exhaust gas, and toxicity evaluation. Thus, the method has the potential to become a standard analytical method for such applications. PMID- 27401813 TI - Effect of reference conditions on flow rate, modifier fraction and retention in supercritical fluid chromatography. AB - When using compressible mobile phases such as fluidic CO2, the density, the volumetric flow rates and volumetric fractions are pressure dependent. The pressure and temperature definition of these volumetric parameters (referred to as the reference conditions) may alter between systems, manufacturers and operating conditions. A supercritical fluid chromatography system was modified to operate in two modes with different definition of the eluent delivery parameters, referred to as fixed and variable mode. For the variable mode, the volumetric parameters are defined with reference to the pump operating pressure and actual pump head temperature. These conditions may vary when, e.g. changing the column length, permeability, flow rate, etc. and are thus variable reference conditions. For the fixed mode, the reference conditions were set at 150bar and 30 degrees C, resulting in a mass flow rate and mass fraction of modifier definition which is independent of the operation conditions. For the variable mode, the mass flow rate of carbon dioxide increases with system pump operating pressure, decreasing the fraction of modifier. Comparing the void times and retention factor shows that the deviation between the two modes is almost independent of modifier percentage, but depends on the operating pressure. Recalculating the set volumetric fraction of modifier to the mass fraction results in the same retention behaviour for both modes. This shows that retention in SFC can be best modelled using the mass fraction of modifier. The fixed mode also simplifies method scaling as it only requires matching average column pressure. PMID- 27401814 TI - Single venous anastomosis versus dual venous anastomoses in free anterolateral thigh flap transfer: A cohort study. PMID- 27401815 TI - Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species. AB - BACKGROUND: Medicinal plants have traditionally been used in many parts of the world as alternative medicine. Many extracts and essential oils isolated from plants have disclosed biological activity, justifying the investigation of their potential antimicrobial activity. In this study, the in vitro antifungal activity of six Brazilian Cerrado medicinal plant species were evaluated against clinically relevant Candida species. METHODS: The crude extract plants were evaluated against American Type Culture Collection (ATCC) standard strains of Candida spp. using disk diffusion method and determining the minimum inhibitory concentration (MIC). The chemical study results were confirmed by HPLC method. RESULTS: All six plant species showed antifungal activity. Among the species studied, Eugenia dysenterica and Pouteria ramiflora showed significant inhibitory activity against C. tropicalis at lowest MIC value of 125 and 500 MUg/disc, respectively. The Eugenia dysenterica also disclosed MIC value of 125 MUg/disc against C. famata, 250 MUg/disc against C. krusei and 500 MUg/disc against C. guilliermondii and C. parapsilosis. Pouteria torta, Bauhinia rufa, Erythroxylum daphnites and Erythroxylum subrotundum showed activity against the yeast strains with MIC value of 1000 MUg/disc. The chemical study of the most bioactive extracts of Eugenia dysenterica and Pouteria ramiflora revealed catechin derivatives and flavonoids as main components. CONCLUSIONS: All six evaluated plant species showed good antifungal potential against several Candida strains. However, E .dysenterica and P. ramiflora showed the higher inhibitory effect against the non-albicans Candida species. Our results may contribute to the continuing search of new natural occurring products with antifungal activity. PMID- 27401816 TI - A liposomal formulation of the synthetic curcumin analog EF24 (Lipo-EF24) inhibits pancreatic cancer progression: towards future combination therapies. AB - BACKGROUND: Pancreatic cancer is one of the most lethal of human malignancies known to date and shows relative insensitivity towards most of the clinically available therapy regimens. 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), a novel synthetic curcumin analog, has shown promising in vitro therapeutic efficacy in various human cancer cells, but insufficient water solubility and systemic bioavailability limit its clinical application. Here, we describe nano encapsulation of EF24 into pegylated liposomes (Lipo-EF24) and evaluation of these particles in preclinical in vitro and in vivo model systems of pancreatic cancer. RESULTS: Transmission electron microscopy and size distribution studies by dynamic light scattering confirmed intact spherical morphology of the formed liposomes with an average diameter of less than 150 nm. In vitro, treatment with Lipo-EF24 induced growth inhibition and apoptosis in MIAPaCa and Pa03C pancreatic cancer cells as assessed by using cell viability and proliferation assays, replating and soft agar clonogenicity assays as well as western blot analyses. Lipo-EF24 potently suppressed NF-kappaB nuclear translocation by inhibiting phosphorylation and subsequent degradation of its inhibitor I-kappa-B-alpha. In vivo, synergistic tumor growth inhibition was observed in MIAPaCa xenografts when Lipo-EF24 was given in combination with the standard-of-care cytotoxic agent gemcitabine. In line with in vitro observations, western blot analysis revealed decreased phosphorylation of I-kappa-B-alpha in excised Lipo-EF24-treated xenograft tumor tissues. CONCLUSION: Due to its promising therapeutic efficacy and favorable toxicity profile Lipo-EF24 might be a promising starting point for development of future combinatorial therapeutic regimens against pancreatic cancer. PMID- 27401817 TI - Dynamic polarization vision in mantis shrimps. AB - Gaze stabilization is an almost ubiquitous animal behaviour, one that is required to see the world clearly and without blur. Stomatopods, however, only fix their eyes on scenes or objects of interest occasionally. Almost uniquely among animals they explore their visual environment with a series pitch, yaw and torsional (roll) rotations of their eyes, where each eye may also move largely independently of the other. In this work, we demonstrate that the torsional rotations are used to actively enhance their ability to see the polarization of light. Both Gonodactylus smithii and Odontodactylus scyllarus rotate their eyes to align particular photoreceptors relative to the angle of polarization of a linearly polarized visual stimulus, thereby maximizing the polarization contrast between an object of interest and its background. This is the first documented example of any animal displaying dynamic polarization vision, in which the polarization information is actively maximized through rotational eye movements. PMID- 27401818 TI - Relationships between the solution and solid-state properties of solution-cast low-k silica thin films. AB - This paper reports on the fabrication of low-k (amorphous) silica thin films cast from solutions without and with two different types of surfactants (TWEEN(r) 80 and TritonTM X-100) to elucidate the relationships between the structural/morphological features of the casting solutions and the physical properties of the resulting thin films. Cryogenic transmission microscopy (cryo TEM), static/dynamic light scattering (SLS/DLS), and small-angle X-ray scattering (SAXS) revealed contrasting colloidal dispersion states and phase behavior among the three casting solutions. Casting solution with the TritonTM X-100 surfactant produced stable (>90 days) nanoparticles with good dispersion in solution (mean particle size ~10 nm) as well as good mesopore volume (characterized by nitrogen physisorption) in powder and thin films of high mechanical strength (characterized by the nanoindentation test). The longer main chain and bulkier side units of the TWEEN(r) 80 surfactant led to stable micelle-nanoparticle coexisting dispersion, which resulted in the highest mesopore volume in powder and thin films with the lowest dielectric constant (~3) among the samples in this study. The casting solution without the surfactant failed to produce a stabilized solution or thin films of acceptable uniformity. These findings demonstrate the possibility of fine-tuning low-k silica film properties by controlling the colloidal state of casting solutions. PMID- 27401820 TI - When left turns to right: a congenital corrected transposition of the great arteries with an azygos continuation without another major cardiac abnormality. PMID- 27401819 TI - Implementation of repeat HIV testing during pregnancy in Kenya: a qualitative study. AB - BACKGROUND: Repeat HIV testing in late pregnancy has the potential to decrease rates of mother-to-child transmission of HIV by identifying mothers who seroconvert after having tested negative for HIV in early pregnancy. Despite being national policy in Kenya, the available data suggest that implementation rates are low. METHODS: We conducted 20 in-depth semi-structured interviews with healthcare providers and managers to explore barriers and enablers to implementation of repeat HIV testing guidelines for pregnant women. Participants were from the Nyanza region of Kenya and were purposively selected to provide variation in socio-demographics and job characteristics. Interview transcripts were coded and analyzed in Dedoose software using a thematic analysis approach. Four themes were identified a priori using Ferlie and Shortell's Framework for Change and additional themes were allowed to emerge from the data. RESULTS: Participants identified barriers and enablers at the client, provider, facility, and health system levels. Key barriers at the client level from the perspective of providers included late initial presentation to antenatal care and low proportions of women completing the recommended four antenatal visits. Barriers to offering repeat HIV testing for providers included heavy workloads, time limitations, and failing to remember to check for retest eligibility. At the facility level, inconsistent volume of clients and lack of space required for confidential HIV retesting were cited as barriers. Finally, at the health system level, there were challenges relating to the HIV test kit supply chain and the design of nationally standardized antenatal patient registers. Enablers to improving the implementation of repeat HIV testing included client dissemination of the benefits of antenatal care through word-of-mouth, provider cooperation and task shifting, and it was suggested that use of an electronic health record system could provide automatic reminders for retest eligibility. CONCLUSIONS: This study highlights some important barriers to improving HIV retesting rates among pregnant women who attend antenatal clinics in the Nyanza region of Kenya at the client, provider, facility, and health system levels. To successfully implement Kenya's national repeat HIV testing guidelines during pregnancy, it is essential that these barriers be addressed and enablers capitalized on through a multi-faceted intervention program. PMID- 27401821 TI - Shear stress with appropriate time-step and amplification enhances endothelial cell retention on vascular grafts. AB - Endothelial cells (ECs) are sensitive to changes in shear stress. The application of shear stress to ECs has been well documented to improve cell retention when placed into a haemodynamically active environment. However, the relationship between the time-step and amplification of shear stress on EC functions remains elusive. In the present study, human umbilical cord veins endothelial cells (HUVECs) were seeded on silk fibroin nanofibrous scaffolds and were preconditioned by shear stress at different time-steps and amplifications. It is shown that gradually increasing shear stress with appropriate time-steps and amplification could improve EC retention, yielding a complete endothelial-like monolayer both in vitro and in vivo. The mechanism of this improvement is mediated, at least in part, by an upregulation of integrin beta1 and focal adhesion kinase (FAK) expression, which contributed to fibronectin (FN) assembly enhancement in ECs in response to the shear stress. A modest gradual increase in shear stress was essential to allow additional time for ECs to gradually acclimatize to the changing environment, with the goal of withstanding the physiological levels of shear stress. This study recognized that the time-steps and amplifications of shear stress could regulate EC tolerance to shear stress and the anti-thrombogenicity function of engineered vascular grafts via an extracellular cell matrix-specific, mechanosensitive signalling pathway and might prevent thrombus formation in vivo. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401823 TI - Research digest. PMID- 27401822 TI - Distribution of Prokaryotic Abundance and Microbial Nutrient Cycling Across a High-Alpine Altitudinal Gradient in the Austrian Central Alps is Affected by Vegetation, Temperature, and Soil Nutrients. AB - Studies of the altitudinal distributions of soil microorganisms are rare or have led to contradictory results. Therefore, we studied archaeal and bacterial abundance and microbial-mediated activities across an altitudinal gradient (2700 to 3500 m) on the southwestern slope of Mt. Schrankogel (Central Alps, Austria). Sampling sites distributed over the alpine (2700 to 2900 m), the alpine-nival (3000 to 3100 m), and the nival altitudinal belts (3200 to 3500 m), which are populated by characteristic plant assemblages. Bacterial and archaeal abundances were measured via quantitative real-time PCR (qPCR). Moreover, microbial biomass C, microbial activity (dehydrogenase), and enzymes involved in carbon (CM cellulase), nitrogen (protease), phosphorus (alkaline phosphatase), and sulfur (arylsulfatase) cycling were determined. Abundances, microbial biomass C, and activities almost linearly decreased along the gradient. Archaeal abundance experienced a sharper decrease, thus pointing to pronounced sensitivity toward environmental harshness. Additionally, abundance and activities were significantly higher in soils of the alpine belt compared with those of the nival belt, whereas the alpine-nival ecotone represented a transitional area with intermediate values, thus highlighting the importance of vegetation. Archaeal abundance along the gradient was significantly related to soil temperature only, whereas bacterial abundance was significantly related to temperature and dissolved organic carbon (DOC). Soil carbon and nitrogen concentrations explained most of the variance in enzyme activities involved in the cycling of C, N, P, and S. Increasing temperature could therefore increase the abundances and activities of microorganisms either directly or indirectly via expansion of alpine vegetation to higher altitudes and increased plant cover. PMID- 27401824 TI - Why sex? PMID- 27401825 TI - Neurotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin. AB - Russell's vipers are snakes of major medical importance in Asia. Russell's viper (Daboia russelii) envenoming in Sri Lanka and South India leads to a unique, mild neuromuscular paralysis, not seen in other parts of the world where the snake is found. This study aimed to identify and pharmacologically characterise the major neurotoxic components of Sri Lankan Russell's viper venom. Venom was fractionated using size exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). In vitro neurotoxicities of the venoms, fractions and isolated toxins were measured using chick biventer and rat hemidiaphragm preparations. A phospholipase A2 (PLA2) toxin, U1-viperitoxin-Dr1a (13.6 kDa), which constitutes 19.2 % of the crude venom, was isolated and purified using HPLC. U1-viperitoxin-Dr1a produced concentration-dependent in vitro neurotoxicity abolishing indirect twitches in the chick biventer nerve-muscle preparation, with a t 90 of 55 +/- 7 min only at 1 MUM. The toxin did not abolish responses to acetylcholine and carbachol indicating pre-synaptic neurotoxicity. Venom, in the absence of U1-viperitoxin-Dr1a, did not induce in vitro neurotoxicity. Indian polyvalent antivenom, at the recommended concentration, only partially prevented the neurotoxic effects of U1-viperitoxin-Dr1a. Liquid chromatography mass spectrometry analysis confirmed that U1-viperitoxin-Dr1a was the basic S-type PLA2 toxin previously identified from this venom (NCBI-GI: 298351762; SwissProt: P86368). The present study demonstrates that neurotoxicity following Sri Lankan Russell's viper envenoming is primarily due to the pre-synaptic neurotoxin U1 viperitoxin-Dr1a. Mild neurotoxicity observed in severely envenomed Sri Lankan Russell's viper bites is most likely due to the low potency of U1-viperitoxin Dr1a, despite its high relative abundance in the venom. PMID- 27401826 TI - Hydroxyurea Treatment and Development of the Rat Cerebellum: Effects on the Neurogenetic Profiles and Settled Patterns of Purkinje Cells and Deep Cerebellar Nuclei Neurons. AB - The current paper analyzes the development of the male and female rat cerebellum exposed to hydroxyurea (HU) (300 or 600 mg/kg) as embryo and collected at postnatal day 90. Our study reveals that the administration of this drug compromises neither the cytoarchitecture of the cerebellar cortex nor deep nuclei (DCN). However, in comparison with the saline group, we observed that several cerebellar parameters were lower in the HU injected groups. These parameters included area of the cerebellum, cerebellar cortex length, molecular layer area, Purkinje cell number, granule cell counts, internal granular layer, white matter and cerebellar nuclei areas, and number of deep cerebellar nuclei neurons. These features were larger in the rats injected with saline, smaller in those exposed to 300 mg/kg of HU and smallest in the group receiving 600 mg/kg of this agent. No sex differences in the effect of the HU were observed. In addition, we infer the neurogenetic timetables and the neurogenetic gradients of PCs and DCN neurons in rats exposed to either saline or HU as embryos. For this purpose, 5-bromo-2' deoxyuridine was injected into pregnant rats previously administered with saline or HU. This thymidine analog was administered following a progressively delayed cumulative labeling method. The data presented here show that systematic differences exist in the pattern of neurogenesis and in the spatial location of cerebellar neurons between rats injected with saline or HU. No sex differences in the effect of the HU were observed. These findings have implications for the administration of this compound to women in gestation as the effects of HU on the development of the cerebellum might persist throughout their offsprings' life. PMID- 27401827 TI - The experiences of frequent users of crisis helplines: A qualitative interview study. AB - OBJECTIVE: To understand why some users call crisis helplines frequently. METHODS: Nineteen semi-structured telephone interviews were conducted with callers to Lifeline Australia who reported calling 20 times or more in the past month and provided informed consent. Interviews were audio-recorded and transcribed verbatim. Inductive thematic analysis was used to generate common themes. Approval was granted by The University of Melbourne Human Research Ethics Committee. RESULTS: Three overarching themes emerged from the data and included reasons for calling, service response and calling behaviours. Respondents called seeking someone to talk to, help with their mental health issues and assistance with negative life events. When they called, they found short-term benefits in the unrestricted support offered by the helpline. Over time they called about similar issues and described reactive, support-seeking and dependent calling behaviours. CONCLUSION: Frequent users of crisis helplines call about ongoing issues. They have developed distinctive calling behaviours which appear to occur through an interaction between their reasons for calling and the response they receive from the helpline. PRACTICE IMPLICATIONS: The ongoing nature of the issues prompting frequent users to call suggests that a service model that includes a continuity of care component may be more efficient in meeting their needs. PMID- 27401828 TI - Characterizing safety-net providers' HPV vaccine recommendations to undecided parents: A pilot study. AB - OBJECTIVE: Although provider recommendation is a key predictor of HPV vaccination, how providers verbalize recommendations particularly strong ones is unknown. We developed a tool to describe strength and content of provider recommendations. METHODS: We used electronic health records to identify unvaccinated adolescents with appointments at six safety-net clinics in Dallas, Texas. Clinic visit audio-recordings were qualitatively analyzed to identify provider recommendation types (presumptive vs. participatory introduction; strong vs. weak), describe content communicated, and explore patterns between recommendation type and vaccination. RESULTS: We analyzed 43 audio-recorded discussions between parents and 12 providers. Most providers used a participatory introduction (42 discussions) and made weak recommendations (24 discussions) by using passive voice or adding a qualification (e.g., not school required). Few providers (11 discussions) gave strong recommendations (clear, personally-owned endorsement). HPV vaccination was lowest for those receiving only weak recommendations and highest when providers coupled the recommendation with an adjacent rationale. CONCLUSION: Our new tool provides initial evidence of how providers undercut their recommendations through qualifications or support them with a rationale. Most providers gave weak HPV vaccine recommendations and used a participatory introduction. PRACTICE IMPLICATIONS: Providers would benefit from communication skills training on how to make explicit recommendations with an evidence-based rationale. PMID- 27401829 TI - Culture and motivational interviewing. PMID- 27401830 TI - Lysinibacillus endophyticus sp. nov., an indole-3-acetic acid producing endophytic bacterium isolated from corn root (Zea mays cv. Xinken-5). AB - A Gram-positive, aerobic, motile, rod-shaped bacterium, designated strain C9(T), was isolated from surface sterilised corn roots (Zea mays cv. Xinken-5) and found to be able to produce indole-3-acetic acid. A polyphasic taxonomic study was carried out to determine the status of strain C9(T). The major cellular fatty acids were found to contain iso-C15:0, anteiso-C15:0 and anteiso-C17:0, and the only menaquinone was identified as MK-7. The polar lipid profile was found to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and an unidentified lipid. The cell wall peptidoglycan was found to be of the A4alpha L-Lys-D-Asp type and the whole cell sugar was found to be glucose. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain C9(T) belongs to the genus Lysinibacillus and is closely related to Lysinibacillus chungkukjangi NBRC 108948(T) (98.1 % similarity) and Lysinibacillus sinduriensis DSM 27595(T) (98.0 %). However, the low levels of DNA-DNA relatedness and some differential phenotypic characteristics allowed the strain to be distinguished from its close relatives. Therefore, it is concluded that strain C9(T) represents a novel species of the genus Lysinibacillus, for which the name Lysinibacillus endophyticus sp. nov. is proposed. The type strain is C9(T) (=DSM 100506(T) = CGMCC 1.15291(T)). PMID- 27401831 TI - Screening of sensitivity to mandipropamid of Plasmopara viticola populations from Italian vineyards by molecular and biological methods. AB - The objective of this work was to study the sensitivity to mandipropamid of 33 Plasmopara viticola populations utilizing both molecular and biological techniques. The PCR-RFLP technique was developed in order to detect the single point mutation, G1105S, occurring on the PvCesA3 gene. The sensitivity was also studied using the leaf-disc bioassay. Thirty-three downy mildew-infected leaf samples, collected from 2010 to 2013 from Italian vineyards, were used in the study. PCR-RFLP revealed the presence of 7 resistant, 12 sensitive, 14 mixed (sensitive and resistant) mutation profiles. Effective concentration for 50% inhibition rate (EC50 ) calculated from the bioassays showed an EC50 < 1 mg l( 1) for samples that showed sensitive profiles, while for those samples that had a mixed profile, EC50 ranged from <1 to >300 mg l(-1) , and values for resistant profiles ranged from 200.28 to >300 mg l(-1) . The results suggest that P. viticola populations infecting Italian vineyards are under a selection pressure due to CAA-based fungicide applications. SIGNIFICANCE AND IMPACT OF THE STUDY: We characterized Plasmopara viticola populations utilizing PCR-RFLP technique to detect a point mutation known to cause resistance to carboxylic acid amides (CAA) fungicides. Sensitivity of these samples to the mandipropamid fungicide was assayed by a leaf-disc method. In this work, we provide the first evidence about the presence of mandipropamid-resistant populations of P. viticola from commercial vineyards in Italy. Improving the knowledge about development of resistant populations could enhance the current grapevine downy mildew management strategies and minimize the risk of the spread of mandipropamid and other CAA resistant populations. PMID- 27401832 TI - Activation of autonomic thermoeffectors preceding the decision to behaviourally thermoregulate in resting humans. AB - What is the central question of this study? Do increases in metabolic heat production and sweat rate precede the initiation of thermoregulatory behaviour in resting humans exposed to cool and warm environments? What is the main finding and its importance? Thermoregulatory behaviour at rest in cool and warm environments is preceded by changes in vasomotor tone in glabrous and non glabrous skin, but not by acute increases in metabolic heat production or sweat rate. These findings suggest that sweating and shivering are not obligatory for thermal behaviour to be initiated in humans. We tested the hypothesis that acute increases in metabolic heat production and sweating precede the initiation of thermoregulatory behaviour in resting humans exposed to cool and warm environments. Twelve healthy young subjects passively moved between 17 and 40 degrees C rooms when they felt 'too cool' (C->W) or 'too warm' (W->C). Skin and internal (intestinal) temperatures, metabolic heat production, local sweat rate (forearm and chest) and cutaneous vascular conductance (CVC; forearm and fingertip) were measured continually. Compared with pretest baseline (31.8 +/- 0.3 degrees C), skin temperature was higher at C->W (32.0 +/- 0.7 degrees C; P = 0.01) and W->C (34.5 +/- 0.5 degrees C; P < 0.01). Internal temperature did not differ (P = 0.12) between baseline (37.2 +/- 0.3 degrees C), C->W (37.2 +/- 0.3 degrees C) and W->C (37.0 +/- 0.3 degrees C). Metabolic heat production was not different from baseline (40 +/- 9 W m-2 ) at C->W (39 +/- 7 W m-2 ; P = 0.50). Forearm (0.06 +/- 0.01 mg cm-2 min-1 ) and chest (0.04 +/- 0.02 mg cm-2 min-1 ) sweat rate at W->C did not differ from baseline (forearm, 0.05 +/- 0.02 mg cm-2 min-1 and chest, 0.04 +/- 0.02 mg cm-2 min-1 ; P >= 0.23). Forearm CVC was not different from baseline (0.30 +/- 0.21 perfusion units (PU) mmHg-1 ) at C->W (0.24 +/- 0.11 PU mmHg-1 ; P = 0.17), but was higher at W->C (0.65 +/- 0.33 PU mmHg-1 ; P < 0.01). Fingertip CVC was different from baseline (2.6 +/- 2.0 PU mmHg-1 ) at C->W (0.70 +/- 0.42 PU mmHg-1 ; P < 0.01) and W->C (4.49 +/- 1.66 PU mmHg-1 ; P < 0.01). Thermoregulatory behaviour at rest in cool and warm environments is preceded by changes in vasomotor tone in glabrous and non glabrous skin, but not by acute increases in metabolic heat production or sweat rate. PMID- 27401833 TI - Reconstruction of an input function from a dynamic PET water image using multiple tissue curves. AB - Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with [Formula: see text] (15)O or C(15)O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic [Formula: see text] (15)O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n = 29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around <8% and the calculated CBF values showed a tight correlation (r = 0.97). The simulation showed that errors associated with the assumed parameters were <10%, and that the optimal number of tissue curves to be used was around 500. Our results demonstrate that IDIF can be reconstructed directly from tissue curves obtained through [Formula: see text] (15)O PET imaging. This suggests the possibility of using a completely non invasive technique to assess CBF in patho-physiological studies. PMID- 27401834 TI - Postoperative Stroke after Debranching with Thoracic Endovascular Aortic Repair. AB - OBJECTIVES: This study aimed to analyze the perioperative stroke rate, stroke lesions, outcome, risk factors, and stroke prevention following debranching with thoracic endovascular aortic repair (TEVAR). DESIGN: Retrospective study. METHODS: Between February 2011 and February 2015, 74 consecutive patients underwent debranching with TEVAR at our institution. Of these, the TEVAR proximal landing zone was "zone 0" in 23 patients, "zone 1" in 28, and "zone 2" in 23. Left subclavian artery (LSA) occlusion with coil embolization, balloon occlusion, or vascular plugging was performed in 27 patients. Mean follow-up time was 19.2 months (range 2-52 months). RESULTS: The in-hospital mortality rate was 4.1%. Stroke developed in 7 patients (9.5%), zone 0 in 4 patients, zone 1 in 2, and zone 2 in 1. Six of these patients had stroke lesions arising from the vertebral/basilar artery. Univariate analysis revealed a significant increase in the risk of postoperative stroke in patients with intraluminal atheroma (P = 0.001), those who underwent prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft (P = 0.002), and those with a long operative duration (P = 0.001). Additionally, LSA occlusion significantly decreased the incidence of stroke (P = 0.041). The postsurgical 1- and 2-year cumulative survival rates were 87.3% and 77.0%, respectively, in those without stroke, and 68.6% and 22.9%, respectively, in those with stroke (P = 0.012). CONCLUSIONS: Stroke after debranching with TEVAR was associated with a high mortality. To prevent stroke, careful patient selection and protection of the vertebral artery are important. Prophylactic LSA occlusion at the time of stent-graft deployment might reduce the risk of perioperative stroke. PMID- 27401835 TI - Coagulation of humic waters for diffused pollution control and the influence of coagulant type on DOC fractions removed. AB - This study examined the suitability of organic coagulants for treatment of typically humic peat extraction runoff water by comparing their performance with that of ferric sulphate (FS). The influence of coagulant type on dissolved organic carbon (DOC) fractions removed was analysed in detail using LC-OCD-OND (size exclusion liquid chromatography coupled with organic carbon and organic nitrogen detection) fractionation techniques. In general, lower coagulant dosage was needed under acidic (pH 4.5) than neutral (pH 6.5) conditions. Chitosan (Chit) and poly (diallyldimethyl) ammonium chloride (pDMAC) required significantly lower dosage (40-55%) than FS for acceptable purification, while a tannin-based coagulant (Tan2) required substantially higher dosage (55-75%) independent of water pH. FS demonstrated the best removal of DOC (<81%) and phosphorus (<93%) followed by pDMAC, while Chit and Tan2 achieved the highest removal of suspended solids (SS) (<58%), with flocs formed by Tan2 presenting the best settling properties. Higher molecular weight (MW) DOC fractions were more efficiently removed by all coagulants, with FS being the most efficient (biopolymers 69% and humic substances 91%), followed by Tan2. FS also displayed satisfactory removal of lower MW fractions (building blocks ~46% and low MW neutrals 62%). Overall, FS was the best performing coagulant. Nevertheless, the organic polymers demonstrated satisfactory overall performance, achieving purification rates mostly inside the requirements set by Finnish environmental authorities. PMID- 27401837 TI - Concise Review: Perspectives and Clinical Implications of Bone Marrow and Circulating Stem Cell Defects in Diabetes. AB - Diabetes mellitus is a complex systemic disease characterized by severe morbidity and excess mortality. The burden of its multiorgan complications relies on an imbalance between hyperglycemic cell damage and defective endogenous reparative mechanisms. Inflammation and abnormalities in several hematopoietic components are typically found in diabetes. The discovery that diabetes reduces circulating stem/progenitor cells and impairs their function has opened an entire new field of study where diabetology comes into contact with hematology and regenerative medicine. It is being progressively recognized that such rare circulating cell populations mirror finely regulated processes involved in hematopoiesis, immunosurveillance, and peripheral tissue homeostasis. From a clinical perspective, pauperization of circulating stem cells predicts adverse outcomes and death. Furthermore, studies in murine models and humans have identified the bone marrow (BM) as a previously neglected site of diabetic end-organ damage, characterized by microangiopathy, neuropathy, fat deposition, and inflammation. As a result, diabetes impairs the mobilization of BM stem/progenitor cells, a defect known as mobilopathy or myelokathexis, with negative consequences for physiologic hematopoiesis, immune regulation, and tissue regeneration. A better understanding of the molecular and cellular processes that govern the BM stem cell niche, cell mobilization, and kinetics in peripheral tissues may uncover new therapeutic strategies for patients with diabetes. This concise review summarizes the current knowledge on the interplay between the BM, circulating stem cells, and diabetes, and sets the stages for future developments in the field. Stem Cells 2017;35:106-116. PMID- 27401836 TI - Designing and delivering facilitated storytelling interventions for chronic disease self-management: a scoping review. AB - BACKGROUND: Little is known about how to develop and deliver storytelling as an intervention to support those managing chronic illnesses. This scoping review aims to describe the core elements of storytelling interventions in order to help facilitate its implementation. METHODS: A scoping review was conducted in seven databases for articles published up to May 2014 to identify interventions that describe in detail how storytelling was used to support people in disease self management interventions. RESULTS: Ten articles met all inclusion criteria. Core elements consistently observed across the storytelling interventions were: reflection and interactive meaning-making of experiences; principles of informality and spontaneity; non-directional and non-hierarchical facilitation; development of group norms and conduct to create a community among participants; and both an individual and collective role for participants. Differences were also observed across interventions, such as: the conceptual frameworks that directed the design of the intervention; the type and training of facilitators; intervention duration; and how session topics were selected and stories delivered. Furthermore, evaluation of the intervention and outcome assessment varied greatly across studies. CONCLUSION: The use of storytelling can be a novel intervention to enhance chronic disease self-management. The core elements identified in the review inform the development of the intervention to be more patient-centred by guiding participants to take ownership of and lead the intervention, which differs significantly from traditional support groups. Storytelling has the potential to provide patients with a more active role in their health care by identifying their specific needs as well as gaps in knowledge and skills, while allowing them to form strong bonds with peers who share similar disease-related experiences. However, measures of impact differed across interventions given the variation in chronic conditions. Our findings can guide future development and implementations of storytelling interventions. PMID- 27401838 TI - Predictors of readmission to non-index hospitals after colorectal surgery. AB - BACKGROUND: Although a significant proportion of patients are readmitted to non index hospitals after surgery, risk factors for non-index hospital readmission are not well defined. METHODS: Using the California Office of State Health Planning and Development database from 2008 to 2012, patients readmitted to index versus non-index hospitals after colorectal surgery were directly compared. Risk factors for non-index hospital readmission were assessed through logistic regression. RESULTS: Among the 14,401 patients requiring readmission, 10,890 (75.6%) were readmitted to index hospitals, whereas 3,511 (24.4%) were readmitted to non-index hospitals. Patients readmitted to non-index hospitals were more likely to be men and have a greater Charlson comorbidity index, non-private insurance, longer initial length of stay, longer travel distance, and non-home discharge disposition. On multivariable logistic regression analysis, living >=10 miles from the index hospital was strongly predictive of non-index hospital readmission (odds ratio, 1.8; 95% confidence interval, 1.63 to 2.00). CONCLUSIONS: Approximately 25% of readmissions after colorectal surgery will be to non-index hospitals. Risks factors include greater comorbidities, non-private health insurance, occurrence of an inpatient complication, longer length of stay, greater travel distance, and non-home discharge disposition. PMID- 27401839 TI - Diagnostic value of intestinal fatty acid-binding protein for pneumatosis intestinalis. AB - BACKGROUND: Pneumatosis intestinalis (PI) is known as a sign of a life threatening bowel ischemia. We aimed to evaluate the utility of intestinal fatty acid-binding protein (I-FABP) in the diagnosis of pathologic PI. METHODS: All consecutive patients who presented to our emergency department with PI were prospectively enrolled. The diagnostic performance of I-FABP for pathologic PI was compared with that of other traditional biomarkers and various parameters. RESULTS: Seventy patients with PI were enrolled. Pathologic PI was diagnosed in 27 patients (39%). The levels of most biomarkers were significantly higher in patients with pathologic PI than those with nonpathologic PI (P < .05). Receiver operator characteristic analysis revealed that the area under the curve (AUC) was highest for I-FABP (area under the curve = .82) in the diagnosis of pathologic PI. CONCLUSIONS: High I-FABP value, in combination with other parameters, might be clinically useful for pathologic PI. PMID- 27401840 TI - Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors. AB - BACKGROUND: The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. METHODS: This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. RESULTS: Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73% 91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. CONCLUSIONS: An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. CONFLICT OF INTEREST STATEMENT: No conflict of interest. PMID- 27401841 TI - Patterns of distant metastases in vulvar cancer. AB - OBJECTIVE: Metastatic vulvar cancer is a rare disease. Information on metastatic patterns and corresponding prognosis or therapeutic approaches is scarce. We therefore analyzed pattern and course of metastatic disease in a large single center cohort. METHODS: All patients with primary squamous-cell cancer of the vulvar [n=391, median age: 60years (range 20-94)] treated at the Gynecological Cancer Center Hamburg-Eppendorf 1996-2013 were retrospectively evaluated for occurrence of distant metastasis. Furthermore, a systematic Medline database search was performed using the terms: 'vulvar cancer' AND 'metastasis', 'chemotherapy', 'patterns of recurrence', or 'prognosis'. RESULTS: Out of 391 patients with primary squamous cell vulvar cancer, 20 patients (5.1%) eventually presented with distant metastases. In these 20 patients, median time to first diagnosis of metastasis after primary diagnosis was 13.4months (range 4-104). Often patients experienced one or more local recurrences before distant spread (12/20, 60.0%). Documented metastatic sites were lung (n=9), liver (n=7), bone (n=5), skin (n=4) and lymph-nodes (axillary/thoracic/paraaortic, n=3). The majority of patients presented with unilocal metastases (13/20, 65.0%). In univariate analysis tumor diameter, invasion depth, nodal status and number of metastatic lymph-nodes were identified predictive for occurrence of distant metastases. 2-year-overall-survival-rate after metastases of all metastatic patients was 11.3%; median survival from first diagnosis of metastases was 5.6months. CONCLUSION: The occurrence of distant metastasis from vulvar cancer is a rare event with very limited prognosis. Further efforts, especially translational research will be crucial to identify prognostic markers as well as therapeutic targets to improve survival in these patients. PMID- 27401843 TI - Editorial. PMID- 27401844 TI - Manifest hair repigmentation associated with etretinate therapy. PMID- 27401842 TI - Novel epigenetic changes in CDKN2A are associated with progression of cervical intraepithelial neoplasia. AB - OBJECTIVE: To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. METHODS: We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. RESULTS: In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. CONCLUSION: Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16(INK4A)/p14(ARF) expression prior to development of malignant disease. PMID- 27401845 TI - Journal of the American Geriatrics Society in Transition: 15 Years of Innovation and Excellence Paves the Way for a Bright Future. PMID- 27401846 TI - Marketing Geriatrics. PMID- 27401848 TI - Use of Cholinesterase Inhibitors Increases Initiation of Urinary Anticholinergics in Persons with Alzheimer's Disease. PMID- 27401847 TI - Predicting 2-Year Risk of Developing Pneumonia in Older Adults without Dementia. AB - OBJECTIVES: To develop three prognostic indices of varying degree of required detail for 2-year pneumonia risk in older adults. DESIGN: Retrospective cohort study. SETTING: Group Health (GH), an integrated healthcare delivery system. PARTICIPANTS: Community-dwelling dementia-free individuals aged 65 and older who had been GH members for at least 2 years before start of follow-up and were enrolled in the Adult Changes in Thought study (N = 3,375; development cohort, n = 2,250; validation cohort, n = 1,125. MEASUREMENTS: Potential pneumonia risk factors were identified from questionnaire data and interviewer assessments of functional status, medical history, smoking and alcohol use, cognitive function, personal care, and problem solving. Risk factors were also identified based on physical measures such as grip strength and gait speed and administrative database information on comorbid illnesses, laboratory tests, and prescriptions dispensed. Incident community-acquired pneumonia was defined presumptively from administrative data and validated using medical record review. RESULTS: Participants (59% female) contributed 12,998 visits at which risk factors were assessed; 642 pneumonia events were observed during follow-up. Age, sex, chronic obstructive pulmonary disease, congestive heart failure, body mass index, and use of inhaled or oral corticosteroids were critical predictors in all prognostic indices. A risk score based on these seven variables, information on which is commonly available in electronic medical records (EMRs), had equal or better performance (c-index = 0.69 in the validation cohort) than scores including more detailed data such as functional status. CONCLUSION: Data commonly available in EMRs can stratify older adults into groups with varying subsequent 2-year pneumonia risk. PMID- 27401849 TI - Missing in the Media: Cancer and Older People. PMID- 27401850 TI - Effect of Health Qigong Mawangdui Daoyinshu on Blood Pressure of Individuals with Essential Hypertension. PMID- 27401851 TI - Aging and Comorbidity Augment Disease Severity and Requirements for Treatment Resources in Older Adults with Lower Extremity Skin and Soft Tissue Infection. PMID- 27401852 TI - Individuals Aged 75 and Older Dying at Night: A Retrospective Cohort Study in a Japanese Acute Care Hospital. PMID- 27401853 TI - Elevated International Normalized Ratio in an Unusual Medication Error. PMID- 27401854 TI - Beers Criteria, the Minimum Data Set, and Hospice. PMID- 27401856 TI - Publication, discovery and interoperability of Clinical Decision Support Systems: A Linked Data approach. AB - BACKGROUND: The high costs involved in the development of Clinical Decision Support Systems (CDSS) make it necessary to share their functionality across different systems and organizations. Service Oriented Architectures (SOA) have been proposed to allow reusing CDSS by encapsulating them in a Web service. However, strong barriers in sharing CDS functionality are still present as a consequence of lack of expressiveness of services' interfaces. Linked Services are the evolution of the Semantic Web Services paradigm to process Linked Data. They aim to provide semantic descriptions over SOA implementations to overcome the limitations derived from the syntactic nature of Web services technologies. OBJECTIVE: To facilitate the publication, discovery and interoperability of CDS services by evolving them into Linked Services that expose their interfaces as Linked Data. MATERIALS AND METHODS: We developed methods and models to enhance CDS SOA as Linked Services that define a rich semantic layer based on machine interpretable ontologies that powers their interoperability and reuse. These ontologies provided unambiguous descriptions of CDS services properties to expose them to the Web of Data. RESULTS: We developed models compliant with Linked Data principles to create a semantic representation of the components that compose CDS services. To evaluate our approach we implemented a set of CDS Linked Services using a Web service definition ontology. The definitions of Web services were linked to the models developed in order to attach unambiguous semantics to the service components. All models were bound to SNOMED-CT and public ontologies (e.g. Dublin Core) in order to count on a lingua franca to explore them. Discovery and analysis of CDS services based on machine interpretable models was performed reasoning over the ontologies built. DISCUSSION: Linked Services can be used effectively to expose CDS services to the Web of Data by building on current CDS standards. This allows building shared Linked Knowledge Bases to provide machine interpretable semantics to the CDS service description alleviating the challenges on interoperability and reuse. Linked Services allow for building 'digital libraries' of distributed CDS services that can be hosted and maintained in different organizations. PMID- 27401857 TI - An information model to support user-centered design of medical devices. AB - The process of engineering design requires the product development team to balance the needs and limitations of many stakeholders, including those of the user, regulatory organizations, and the designing institution. This is particularly true in medical device design, where additional consideration must be given for a much more complex user-base that can only be accessed on a limited basis. Given this inherent challenge, few projects exist that consider design domain concepts, such as aspects of a detailed design, a detailed view of various stakeholders and their capabilities, along with the user-needs simultaneously. In this paper, we present a novel information model approach that combines a detailed model of design elements with a model of the design itself, customer requirements, and of the capabilities of the customer themselves. The information model is used to facilitate knowledge capture and automated reasoning across domains with a minimal set of rules by adopting a terminology that treats customer and design specific factors identically, thus enabling straightforward assessments. A uniqueness of this approach is that it systematically provides an integrated perspective on the key usability information that drive design decisions towards more universal or effective outcomes with the very design information impacted by the usability information. This can lead to cost efficient optimal designs based on a direct inclusion of the needs of customers alongside those of business, marketing, and engineering requirements. Two case studies are presented to show the method's potential as a more effective knowledge management tool with built-in automated inferences that provide design insight, as well as its overall effectiveness as a platform to develop and execute medical device design from a holistic perspective. PMID- 27401858 TI - E-cigarettes may be reversing fall in teenage smoking, study finds. PMID- 27401859 TI - Indications for Aortic Arch Intervention. AB - Surgery of the aortic arch is arguably one of the most complex areas of cardiac surgery. Despite that, studies and guidelines have not sufficiently addressed the aortic arch specifically. In general, indications for aortic arch intervention parallel those of the ascending aorta. Herein we review indications for aortic arch intervention in various aortic pathologies based on the scant evidence available combined with surgical expertise and expert opinion. PMID- 27401860 TI - A Rare Case of Anomalous Left Coronary Artery From the Pulmonary Artery (Bland White-Garland Syndrome) in a 68-Year-Old Woman. AB - Anomalous left coronary artery from the pulmonary artery (ALCAPA), or Bland-White Garland syndrome, is a rare congenital coronary anomaly that results in altered myocardial perfusion and a left to right shunt. It occurs in 1:300000 live births and represents 0.24% to 0.46% of all congenital cardiac diseases. Despite its rarity, it is one of the most common causes of ischemia and infarction in children. Ninety percent of these patients will die within the first year of life if untreated and diagnosing this abnormality in adulthood is extremely rare. Of those patients who survive to adulthood, the average age of sudden cardiac death is 35 years. The initial symptoms of the adult presentation vary widely from progressive dyspnea to sudden cardiac death; therefore, immediate surgical correction is highly recommended upon diagnosis. Understanding the pathophysiology and nature of collateral coronary flow in this congenital anomaly is paramount to the safe anesthetic management of adults with ALCAPA. Here we describe the intraoperative management and echocardiographic findings in a 68 year-old with with recently diagnosed ALCAPA undergoing surgical repair. PMID- 27401861 TI - Transcriptomic response of yeast cells to ATX1 deletion under different copper levels. AB - BACKGROUND: Iron and copper homeostatic pathways are tightly linked since copper is required as a cofactor for high affinity iron transport. Atx1p plays an important role in the intracellular copper transport as a copper chaperone transferring copper from the transporters to Ccc2p for its subsequent insertion into Fet3p, which is required for high affinity iron transport. RESULTS: In this study, genome-wide transcriptional landscape of ATX1 deletants grown in media either lacking copper or having excess copper was investigated. ATX1 deletants were allowed to recover full respiratory capacity in the presence of excess copper in growth environment. The present study revealed that iron ion homeostasis was not significantly affected by the absence of ATX1 either at the transcriptional or metabolic levels, suggesting other possible roles for Atx1p in addition to its function as a chaperone in copper-dependent iron absorption. The analysis of the transcriptomic response of atx1?/atx1? and its integration with the genetic interaction network highlighted for the first time, the possible role of ATX1 in cell cycle regulation, likewise its mammalian counterpart ATOX1, which was reported to play an important role in the copper-stimulated proliferation of non-small lung cancer cells. CONCLUSIONS: The present finding revealed the dispensability of Atx1p for the transfer of copper ions to Ccc2p and highlighted its possible role in the cell cycle regulation. The results also showed the potential of Saccharomyces cerevisiae as a model organism in studying the capacity of ATOX1 as a therapeutic target for lung cancer therapy. PMID- 27401862 TI - From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network. AB - OBJECTIVE: Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), which encompasses rare, related and highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and the results of an in vitro assay to measure Gsa protein activity. However, this classification disregards other related diseases such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), as well as recent findings of clinical and genetic/epigenetic background of the different subtypes. Therefore, the EuroPHP network decided to develop a new classification that encompasses all disorders with impairments in PTH and/or PTHrP cAMP-mediated pathway. DESIGN AND METHODS: Extensive review of the literature was performed. Several meetings were organised to discuss about a new, more effective and accurate way to describe disorders caused by abnormalities of the PTH/PTHrP signalling pathway. RESULTS AND CONCLUSIONS: After determining the major and minor criteria to be considered for the diagnosis of these disorders, we proposed to group them under the term 'inactivating PTH/PTHrP signalling disorder' (iPPSD). This terminology: (i) defines the common mechanism responsible for all diseases; (ii) does not require a confirmed genetic defect; (iii) avoids ambiguous terms like 'pseudo' and (iv) eliminates the clinical or molecular overlap between diseases. We believe that the use of this nomenclature and classification will facilitate the development of rationale and comprehensive international guidelines for the diagnosis and treatment of iPPSDs. PMID- 27401863 TI - Treatment with high doses of pegvisomant in 56 patients with acromegaly: experience from ACROSTUDY. AB - OBJECTIVE: To investigate the characteristics of patients who need more or less pegvisomant (PEGV) to normalize serum IGF-I. DESIGN: ACROSTUDY is a global noninterventional safety surveillance study of long-term treatment outcomes in patients treated with PEGV. As of June, 2014, ACROSTUDY included data on 2016 patients. All patients treated for at least 6weeks at a dose above 30mg/day and who had two consecutive normal serum IGF-I values were included in the 'high' dose group (H; n=56; mean daily dose 44+/-12.5; median dose 40, 35-60 (10-90%)). Patients with two consecutive normal IGF-I values and who never received a PEGV dose above 10mg/day were included in the 'low'-dose group (L; n=368; mean daily dose 7.5+/-2.5; median dose 8.6, 4.3-10 (10-90%)). RESULTS: Patients in the H group were significantly younger (median 47 vs 52years) and had a significantly higher BMI (median 31.8 vs 26.5kg/m(2)). They had more diabetes (55% vs 21%), sleep apnea (25% vs 14 %) and more hypertension (61% vs 43%). The incidence of (serious) adverse events was low and was not different between the groups. CONCLUSIONS: Patients who need more PEGV to normalize IGF-I have more aggressive disease, as they are younger, have higher baseline IGF-I levels, more hypertension, more sleep apnea and diabetes and are more overweight. A better understanding of this dose-efficacy relationship of PEGV might avoid inappropriate dosing and prevent serum IGF-I levels from remaining unnecessarily uncontrolled. PMID- 27401864 TI - The relation between changes in thyroid function and anthropometric indices during long-term follow-up of euthyroid subjects: the Tehran Thyroid Study (TTS). AB - OBJECTIVE: Uncertainties exist regarding the causal relationship between thyroid function tests (TFT) within the euthyroid range and anthropometric measures. This longitudinal cohort is aimed to examine the relationship between the two conditions. SUBJECTS AND METHODS: Euthyroid participants of Tehran Thyroid Study (TTS) attending phase I (1999-2001) were included in this study and were followed up to phase IV (2008-2011). TSH and free T4 (fT4) levels as well as weight (Wt), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR) were measured at both phases. RESULTS: 971 women and 784 men were included in the analysis. During 9.7years of follow-up, increases in TSH levels, Wt and WHR as well as a decrease in fT4 level were observed. Multivariable regression analysis showed a significant relationship between TSH changes and alterations in WC in women (beta=0.69, P=0.021) and men (beta=0.61, P=0.038). Moreover, a significant negative association of DeltafT4 with changes in weight was documented (beta= 0.49, P=0.001 in women and beta=-0.56, P<0.001 in men). Additionally, we found a negative relationship between DeltafT4 and DeltaHC in men (beta=-0.36, P=0.001). CONCLUSION: In both genders, there was a positive relationship between changes in TSH and waist circumference and conversely a negative association of changes of fT4 levels with weight over time. PMID- 27401867 TI - Found in translation - EJI gets a facelift. PMID- 27401865 TI - Prevalence, barriers and factors associated with parental disclosure of their HIV positive status to children: a cross-sectional study in an urban clinic in Kampala, Uganda. AB - BACKGROUND: Disclosure of parental HIV status is associated with a number of positive outcomes such as improved adherence to clinic appointments, lower levels of parental anxiety and depression, and mutual emotional support between parents and their children. Very few studies in low-resource settings have addressed the issues of parental disclosure of their HIV status to their children. METHODS: A cross-sectional study was conducted among adult parents attending HIV/AIDS prevention, care and treatment clinic at Makerere University Infectious Diseases Institute (IDI), Kampala, Uganda. Participants were interviewed using the Parent Disclosure Interview (PDI) questionnaire which is a standard tool developed specifically for HIV infected parents. Data were analyzed using STATA version 13.1. RESULTS: Of 344 participants, only 37 % had told at least one of their children that they were HIV positive. Barriers to disclosure were fear that children may tell other people about the parent's HIV status, desire not to worry or upset children and perceptions that children may not understand. Age of the parent, religion and having someone committed to care of the children were positively associated with parental disclosure of their HIV positives status. Attainment of tertiary level of education was negatively associated with parental disclosure of their HIV status. CONCLUSIONS: Parental disclosure of a positive HIVstatus to their children is still low in urban Kampala. There is therefore need to develop locally relevant interventions so as to increase rates of parental disclosure of a positive HIV status to their children and thus promote open and honest discussions about HIV/AIDS at family level. PMID- 27401871 TI - CD28 days later: Resurrecting costimulation for CD8(+) memory T cells. AB - Rapid activation and proliferative expansion of specific CD8(+) memory T (CD8(+) TM ) cells upon antigen re-encounter is a critical component of the adaptive immune response that confers enhanced immune protection. In this context, however, the requirements for costimulation in general, and CD28 signaling in particular, remain incompletely defined. In the current issue of the European Journal of Immunology, Frohlich et al. [Eur. J. Immunol. 2016. 46: 1644-1655] provide definitive evidence that optimal elaboration of CD8(+) TM -cell recall responses is indeed contingent on CD28 expressed by these cells. Here, we discuss the "CD28 costimulation paradigm" in its historical context and highlight some of the unresolved complexities pertaining to CD28-dependent interactions that shape CD8(+) T-cell phenotypes, functionalities, and recall reactivity. PMID- 27401874 TI - Successful sofosbuvir treatment with ribavirin dose reduction for chronic hepatitis C virus genotype 2 infection in a patient with ulcerative colitis: a case report. AB - BACKGROUND: Ulcerative colitis is a lifelong, immunologically mediated disease. Direct-acting antivirals (DAAs) are now available for the treatment of chronic hepatitis C virus (HCV) infection. An interferon-free regimen appears useful, safe and effective for many patients for whom interferon-based treatment is contraindicated. CASE PRESENTATION: We studied a 56-year-old treatment-naive Japanese man with chronic HCV genotype 2b infection who had ulcerative colitis. This patient was treated with sofosbuvir and ribavirin for 12 weeks. During treatment, diarrhoea and bloody faeces were frequent. After ribavirin was reduced to 400 mg daily, these symptoms decreased. Finally, the patient achieved a sustained virologic response 12 weeks after the stoppage of the treatment. CONCLUSION: Clinicians should pay careful attention to the ribavirin dose in the treatment of certain HCV patients with inflammatory bowel disease who are receiving sofosbuvir plus ribavirin. PMID- 27401875 TI - Anterior versus posterior approach in Lenke 5C adolescent idiopathic scoliosis: a meta-analysis of fusion segments and radiological outcomes. AB - BACKGROUND: Radiological outcomes between anterior and posterior approach in Lenke 5C curves were still controversial. Meta-analysis on published articles to compare fusion segments and radiological outcomes between the two surgical approaches was performed. METHODS: Electronic database was conducted for searching studies concerning the anterior versus posterior approach in Lenke 5C curves. After quality assessment, data of means, standard deviations, and sample sizes were extracted. RevMan 5.3 was adopted for data analysis. RESULTS: Seven case-control studies involving 308 Lenke 5C AIS patients were identified in the meta-analysis. No significant differences were noted in correction rate of thoracolumbar/lumbar curve (95 % CI -6.02 to 4.32, P = 0.75) and incidence of proximal junctional kyphosis (95 % CI 0.12 to 7.19, P = 0.94) of final follow-up, in change values of thoracolumbar/lumbar curve (95 % CI -3.28 to 7.19, P = 0.46) and thoracic kyphosis (95 % CI -4.10 to 0.13, P = 0.07). The anterior approach represented a significant shorter fusion segments compared to posterior approach (95 % CI -1.72 to -0.71, P < 0.00001). The posterior approach obtained a larger increasing Cobb angle of lumbar lordosis than the anterior approach (95 % CI 6.06 to -0.61, P = 0.02). CONCLUSIONS: The anterior and posterior approach can obtain comparable coronal correction, change values of thoracic kyphosis, and incidence of proximal junctional kyphosis. The anterior approach saves approximate one more fusion segment, and the posterior approach can obtain a larger increasing Cobb angle of lumbar lordosis, from preoperation to final follow-up. TRIAL REGISTRATION: The article type of this study is meta-analysis and prospective registration is not required. PMID- 27401876 TI - Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice. AB - Renin-angiotensin system (RAS) activity increases under hyperglycemic states, and is thought to be involved in diabetic complications. We previously demonstrated that angiotensin (Ang) II, a main bioactive component of the RAS, might act as a neurotransmitter and/or neuromodulator in the transmission of nociceptive information in the spinal cord. Here, we examined whether the spinal Ang II system is responsible for diabetic neuropathic pain induced by streptozotocin (STZ). Tactile allodynia was observed concurrently with an increase in blood glucose levels the day after mice received STZ (200 mg/kg, i.v.) injections. Tactile allodynia on day 14 was dose-dependently inhibited by intrathecal administration of losartan, an Ang II type 1 (AT1) receptor antagonist, but not by PD123319, an AT2 receptor antagonist. In the lumbar dorsal spinal cord, the expression of Ang II, Ang converting enzyme (ACE), and phospho-p38 mitogen activated protein kinase (MAPK) were all significantly increased on day 14 after STZ injection compared with vehicle-treated controls, whereas no differences were observed among AT1 receptors or angiotensinogen levels. Moreover, the increase in phospho-p38 MAPK was significantly inhibited by intrathecal administration of losartan. These results indicate that the expression of spinal ACE increased in STZ-induced diabetic mice, which in turn led to an increase in Ang II levels and tactile allodynia. This increase in spinal Ang II was accompanied by the phosphorylation of p38 MAPK, which was shown to be mediated by AT1 receptors. PMID- 27401879 TI - Fate of Bisphenol A in Terrestrial and Aquatic Environments. AB - Bisphenol A (2,2-bis[4-hydroxyphenyl]propane, BPA), the monomer used to produce polycarbonate plastic and epoxy resins, is weakly estrogenic and therefore of environmental and human health interest. Due to the high production volumes and disposal of products made from BPA, polycarbonate plastic and epoxy resins, BPA has entered terrestrial and aquatic environments. In the presence of oxygen, diverse taxa of bacteria, fungi, algae and even higher plants metabolize BPA, but anaerobic microbial degradation has not been documented. Recent reports demonstrated that abiotic processes mediate BPA transformation and mineralization in the absence of oxygen, indicating that BPA is susceptible to degradation under anoxic conditions. This review summarizes biological and nonbiological processes that lead to BPA transformation and degradation, and identifies research needs to advance predictive understanding of the longevity of BPA and its transformation products in environmental systems. PMID- 27401878 TI - Nutrition and skin. AB - Nutrition has long been associated with skin health, including all of its possible aspects from beauty to its integrity and even the aging process. Multiple pathways within skin biology are associated with the onset and clinical course of various common skin diseases, such as acne, atopic dermatitis, aging, or even photoprotection. These conditions have been shown to be critically affected by nutritional patterns and dietary interventions where well-documented studies have demonstrated beneficial effects of essential nutrients on impaired skin structural and functional integrity and have restored skin appearance and health. Although the subject could be vast, the intention of this review is to provide the most relevant and the most well-documented information on the role of nutrition in common skin conditions and its impact on skin biology. PMID- 27401877 TI - Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors. AB - Glycine receptors (GlyR) are inhibitory Cys-loop ion channels that contribute to the control of excitability along the central nervous system (CNS). GlyR are found in the spinal cord and brain stem, and more recently they were reported in higher regions of the CNS such as the hippocampus and nucleus accumbens. GlyR are involved in motor coordination, respiratory rhythms, pain transmission, and sensory processing, and they are targets for relevant physiologic and pharmacologic modulators. Several studies with protein crystallography and cryoelectron microscopy have shed light on the residues and mechanisms associated with the activation, blockade, and regulation of pentameric Cys-loop ion channels at the atomic level. Initial studies conducted on the extracellular domain of acetylcholine receptors, ion channels from prokaryote homologs-Erwinia chrysanthemi ligand-gated ion channel (ELIC), Gloeobacter violaceus ligand-gated ion channel (GLIC)-and crystallized eukaryotic receptors made it possible to define the overall structure and topology of the Cys-loop receptors. For example, the determination of pentameric GlyR structures bound to glycine and strychnine have contributed to visualizing the structural changes implicated in the transition between the open and closed states of the Cys-loop receptors. In this review, we summarize how the new information obtained in functional, mutagenesis, and structural studies have contributed to a better understanding of the function and regulation of GlyR. PMID- 27401880 TI - Maternal Depression and Youth Internalizing and Externalizing Symptomatology: Severity and Chronicity of Past Maternal Depression and Current Maternal Depressive Symptoms. AB - Maternal depression is a well-documented risk factor for youth depression, and taking into account its severity and chronicity may provide important insight into the degree of risk conferred. This study explored the degree to which the severity/chronicity of maternal depression history explained variance in youth internalizing and externalizing symptoms above and beyond current maternal depressive symptoms among 171 youth (58 % male) ages 8 to 12 over a span of 3 years. Severity and chronicity of past maternal depression and current maternal depressive symptoms were examined as predictors of parent-reported youth internalizing and externalizing symptomatology, as well as youth self-reported depressive symptoms. Severity and chronicity of past maternal depression did not account for additional variance in youth internalizing and externalizing symptoms at Time 1 beyond what was accounted for by maternal depressive symptoms at Time 1. Longitudinal growth curve modeling indicated that prior severity/chronicity of maternal depression predicted levels of youth internalizing and externalizing symptoms at each time point when controlling for current maternal depressive symptoms at each time point. Chronicity of maternal depression, apart from severity, also predicted rate of change in youth externalizing symptoms over time. These findings highlight the importance of screening and assessing for current maternal depressive symptoms, as well as the nature of past depressive episodes. Possible mechanisms underlying the association between severity/chronicity of maternal depression and youth outcomes, such as residual effects from depressive history on mother-child interactions, are discussed. PMID- 27401881 TI - Prospective Relations between Overeating, Loss of Control Eating, Binge Eating, and Depressive Symptoms in a School-Based Sample of Adolescents. AB - A sample of 353 community adolescents (grades 9 to 12, 57.6 % female) participated in a 2-wave longitudinal study of eating behaviors (overeating, loss of control eating [LOC], and binge eating) and depression. The study addresses 4 hypotheses. (1) The prospective relations between eating behaviors and depressive symptoms will be reciprocal, with each predicting the other over time. (2) These relations will be stronger for girls than for boys. (3) These relations will be stronger for adolescents with high (not low) body mass index (BMI). (4) LOC will show incremental predictive utility in relation to depressive symptoms over and above overeating. Evidence supported reciprocal relations between binge eating and depressive symptoms and between overeating and depressive symptoms, but not between LOC and depressive symptoms. Sex and BMI did not substantially moderate these relations. Taken separately, overeating but not LOC predicted depressive symptoms. Taken together, neither predictor was significant controlling for the other. Results raise questions about the importance of LOC alone in predicting depressive symptoms in adolescence. PMID- 27401883 TI - Naltrexone: A Pan-Addiction Treatment? AB - Addiction is a major public health problem with few efficacious and safe treatments. The goal of this review is to provide an evidence-based assessment of the therapeutic role of the opioid antagonist naltrexone across the addiction spectrum-substance-based and behavioral. The PubMed database was searched for randomized, placebo-controlled clinical trials that investigated the oral or intramuscular long-acting formulation of naltrexone in substance use disorders or behavioral addictions such as pathological gambling, kleptomania, and trichotillomania. Thirty-nine efficacy studies were retrieved, covering alcohol use disorder (n = 22), opioid use disorder (n = 6), nicotine use disorder (n = 5), stimulant use disorder (n = 2), gambling disorder (n = 2), trichotillomania (n = 1), and kleptomania (n = 1). Despite the very different presentations within and between both addiction categories, the data, as a whole, show consistency in favor of naltrexone's relative efficacy and safety. Given the potential benefit and good tolerability revealed in the studies, the high morbidity associated with addiction, and the dearth of alternate treatments, naltrexone would seem like an underutilized treatment option. Further, naltrexone's seemingly broad anti addiction efficacy supports a shared role for brain opioid pathways in the pathophysiology of addiction, broadly defined. More studies investigating the efficacy and tolerability of naltrexone and other opioid modulators are warranted. Studies should also further examine the effect of combining psychotherapy with naltrexone, as well as the potential role of naltrexone in treating comorbid addictions. PMID- 27401882 TI - Sleep and Quality of Life Under Prolonged Release Oxycodone/Naloxone for Severe Restless Legs Syndrome: An Analysis of Secondary Efficacy Variables of a Double Blind, Randomized, Placebo-Controlled Study with an Open-Label Extension. AB - OBJECTIVE: The aim was to assess the effects of prolonged release oxycodone/naloxone (OXN PR) on sleep and quality of life (QoL) in patients with severe restless legs syndrome (RLS) refractory to first-line dopaminergic RLS treatment. METHODS: Sleep and QoL data from a 12-week, randomized, double-blind, placebo-controlled study with subsequent 40-week, open-label extension were analyzed. Instruments included the Medical Outcomes Study (MOS) sleep scale, RLS 6 rating scale, and RLS-QoL questionnaire. RESULTS: The full analysis population included 132 OXN PR and 144 placebo patients. After 12 treatment weeks, improvements in the MOS domains 'sleep disturbance' [-18.6; 95 % confidence interval (CI) -24.4 to -12.9; p < 0.0001], 'sleep adequacy' (14.9; 95 % CI 7.9 21.9; p < 0.0001), and 'sleep quantity' (0.77 h; 95 % CI 0.43-1.11; p < 0.0001) were significantly greater under OXN PR than under placebo. OXN PR also reduced symptom severity (when falling asleep and during the night) and daytime tiredness, and increased sleep satisfaction to a significantly greater extent than placebo (all p < 0.001; RLS-6). QoL improved in both treatment arms, with a significant difference of -9.02 (95 % CI -12.85 to -5.19; p < 0.001) in the mean sum score in favor of OXN PR. All sleep and QoL aspects also improved under 40 weeks of open-label OXN PR treatment. CONCLUSIONS: OXN PR improved RLS symptom severity and sleep quantity and adequacy, resulting in greater sleep satisfaction, less daytime tiredness, and improved QoL. In appropriate patients, OXN PR should be considered as an alternative treatment option for severe RLS that cannot be controlled by first-line dopaminergic medications. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01112644) and EudraCT (2009-011107-23). PMID- 27401885 TI - Effects of high peanut meal with different crude protein level supplemented with amino acids on performance, carcass traits and nitrogen retention of Chinese Yellow broilers. AB - This study assessed the effects of feeding high peanut meal diets of reduced crude protein (CP) content supplemented with essential amino acids (EAA) on growth performance, carcass traits, biochemical indices in plasma, and nitrogen (N) retention of male and female Lingnan Yellow broilers from day 22 to day 42 of age. Each of four dietary treatments (19%, 18%, 17% or 16% CP, dietary CP level reduced by the reduced dietary peanut meal) contained six replicate pens with 35 birds of each sex (males and females with equal number), separately (1680 in total). The three diets with reduced CP were supplemented with 5 EAA to meet the requirements and provide the same levels as in the 19% CP diet. Average daily gain decreased and feed:gain ratio was worse in both sexes with reduced CP% (linear, p < 0.05). Dressing percentage increased as CP% decreased in males (linear, p < 0.05) and thigh muscle percentage reduced slightly in females (linear, p < 0.05). Abdominal fat percentage of males fed the 17% CP was the lowest (quadratic, p < 0.05). The plasma metabolic indices, concentrations of triglycerides and malondialdehyde, showed linear responses to reduced CP% (p < 0.05) with triglycerides increasing while malondialdehyde decreased. Plasma uric acid increased in females (linear, p < 0.05), but not in males, as CP% decreased. Efficiency of N retention increased and N excretion strikingly decreased with lower CP diets (p < 0.001), and both variables showed significant (p < 0.05) linear and quadratic effects. It is concluded that there was a limit to which dietary CP of broilers could be reduced without adverse effects. Dietary CP could be reduced to 17% for males and 18% for females (or 18% when fed together) between day 22 and day 42, if diets are supplemented with synthetic EAA. PMID- 27401884 TI - Healthy Learning Mind - a school-based mindfulness and relaxation program: a study protocol for a cluster randomized controlled trial. AB - BACKGROUND: Mindfulness has shown positive effects on mental health, mental capacity and well-being among adult population. Among children and adolescents, previous research on the effectiveness of mindfulness interventions on health and well-being has shown promising results, but studies with methodologically sound designs have been called for. Few intervention studies in this population have compared the effectiveness of mindfulness programs to alternative intervention programs with adequate sample sizes. METHODS/DESIGN: Our primary aim is to explore the effectiveness of a school-based mindfulness intervention program compared to a standard relaxation program among a non-clinical children and adolescent sample, and a non-treatment control group in school context. In this study, we systematically examine the effects of mindfulness intervention on mental well-being (primary outcomes being resilience; existence/absence of depressive symptoms; experienced psychological strengths and difficulties), cognitive functions, psychophysiological responses, academic achievements, and motivational determinants of practicing mindfulness. The design is a cluster randomized controlled trial with three arms (mindfulness intervention group, active control group, non-treatment group) and the sample includes 59 Finnish schools and approx. 3 000 students aged 12-15 years. Intervention consists of nine mindfulness based lessons, 45 mins per week, for 9 weeks, the dose being identical in active control group receiving standard relaxation program called Relax. The programs are delivered by 14 educated facilitators. Students, their teachers and parents will fill-in the research questionnaires before and after the intervention, and they will all be followed up 6 months after baseline. Additionally, students will be followed 12 months after baseline. For longer follow-up, consent to linking the data to the main health registers has been asked from students and their parents. DISCUSSION: The present study examines systematically the effectiveness of a school-based mindfulness program compared to a standard relaxation program, and a non-treatment control group. A strength of the current study lies in its methodologically rigorous, randomized controlled study design, which allows novel evidence on the effectiveness of mindfulness over and above a standard relaxation program. TRIAL REGISTRATION: ISRCTN18642659 . Retrospectively registered 13 October 2015. PMID- 27401887 TI - Cost-Effectiveness Analysis of Using Loss of Heterozygosity to Manage Premalignant Oral Dysplasia in British Columbia, Canada. AB - BACKGROUND: Management of low-grade oral dysplasias (LGDs) is complicated, as only a small percentage of lesions will progress to invasive disease. The current standard of care requires patients to undergo regular monitoring of their lesions, with intervention occurring as a response to meaningful clinical changes. Recent improvements in molecular technologies and understanding of the biology of LGDs may allow clinicians to manage lesions based on their genome guided risk. METHODS: We used a decision-analytic Markov model to estimate the cost-effectiveness of risk-stratified care using a genomic assay. In the experimental arm, patients with LGDs were managed according to their risk profile using the assay, with low- and intermediate-risk patients given longer screening intervals and high-risk patients immediately treated with surgery. Patients in the comparator arm had standard care (biannual follow-up appointments at an oral cancer clinic). Incremental costs and outcomes in life-years gained (LYG) and quality-adjusted life-years (QALY) were calculated based on the results in each arm. RESULTS: The mean cost of assay-guided management was $8,123 (95% confidence interval [CI] $2,973 to $23,062 in 2013 Canadian dollars) less than the cost of standard care. This difference was driven largely by reductions in resource use among people who did not develop cancer. Mean incremental effectiveness was 0.18 LYG (95% CI 0.08 to 0.39) or 0.64 QALY (95% CI 0.46 to 0.89). Sensitivity analysis suggests that these findings are robust to both expected and extreme variation in all parameter values. CONCLUSION: Use of the assay-guided management strategy costs less and is more effective than standard management of LGDs. IMPLICATIONS FOR PRACTICE: The findings of this study strongly suggest that the use of a risk-stratification method such as a genomic assay can result in improved quality-adjusted survival outcomes for patients with low-grade oral dysplasia (LGD). The use of such an assay in this study provides "precision medicine," allowing for a change in follow-up frequency or early intervention as compared with current standard care. As genomic technologies become more common in cancer care, it is hoped that such an assay, once validated, will become part of a new model for the standard management of LGDs in similar health systems. PMID- 27401886 TI - Biology and Management of Patients With Triple-Negative Breast Cancer. AB - : Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared with other breast cancer subtypes. Because of the lack of approved targeted therapy, at present chemotherapy remains the mainstay of treatment for early and advanced disease. TNBC is enriched for germline BRCA mutation, providing a foundation for the use of this as a biomarker to identify patients suitable for treatment with DNA damaging agents. Inherited and acquired defects in homologous recombination DNA repair, a phenotype termed "BRCAness," may be present in a large proportion of TNBC cases, making it an attractive selection and response biomarker for DNA damaging therapy. Triple-negative breast cancer is a diverse entity for which additional subclassifications are needed. Increasing understanding of biologic heterogeneity of TNBC has provided insight into identifying potentially effective systemic therapies, including cytotoxic and targeted agents. Numerous experimental approaches are under way, and several encouraging drug classes, such as immune checkpoint inhibitors, poly(ADP-ribose) polymerase inhibitors, platinum agents, phosphatidylinositol-3-kinase pathway inhibitors, and androgen receptor inhibitors, are being investigated in TNBC. Molecular biomarker-based patient selection in early-phase trials has the potential to accelerate development of effective therapies for this aggressive breast cancer subtype. TNBC is a complex disease, and it is likely that several different targeted approaches will be needed to make meaningful strides in improving the outcomes. IMPLICATIONS FOR PRACTICE: Triple-negative breast cancer (TNBC) is an aggressive subtype that is associated with poor outcomes. This article reviews clinical features and discusses the molecular diversity of this unique subtype. Current treatment paradigms, the role of germline testing, and platinum agents in TNBC are reviewed. Results and observations from pertinent clinical trials with potential implications for patient management are summarized. This article also discusses the clinical development and ongoing clinical trials of novel promising therapeutic agents in TNBC. PMID- 27401888 TI - Chromosome 17p Homodisomy Is Associated With Better Outcome in 1p19q Non Codeleted and IDH-Mutated Gliomas. AB - BACKGROUND: The 1p19q non-codeleted gliomas with IDH mutation, defined as "molecular astrocytomas," display frequent TP53 mutations and have an intermediate prognosis. We investigated the prognostic impact of copy number neutral loss of heterozygosity (CNLOH) in 17p in this population. METHODS: We analyzed 793 gliomas (206 grade II, 377 grade III, and 210 grade IV) by single nucleotide polymorphism array and for TP53 mutations. RESULTS: Homodisomy revealed by CNLOH was observed in 156 cases (19.7%). It was more frequent in astrocytomas and oligoastrocytomas (98/256, 38%) than oligodendrogliomas (28/327, 8.6%; p < .0001) or glioblastoma multiforme (30/210, 14.3%; p < .0001), tightly associated with TP53 mutation (69/71 vs. 20/79; p = 2 * 10(-16)), and mutually exclusive with 1p19q codeletion (1/156 vs. 249/556; p < .0001). In the group of IDH-mutated 1p19q non-codeleted gliomas, CNLOH 17p was associated with longer survival (86.3 vs. 46.2 months; p = .004), particularly in grade III gliomas (overall survival >100 vs. 37.9 months; p = .007). These data were confirmed in an independent dataset from the Cancer Genome Atlas. CONCLUSION: CNLOH 17p is a prognostic marker and further refines the molecular classification of gliomas. IMPLICATIONS FOR PRACTICE: Homodisomy of chromosome 17p (CNLOH 17p) is a frequent feature in IDH-mutated 1p19q non-codeleted gliomas (group 2). It is constantly associated with TP53 mutation. It was found, within this specific molecular group of gliomas (corresponding to molecular astrocytomas), that CNLOH 17p is associated with a much better outcome and may therefore represent an additional prognostic marker to refine the prognostic classification of gliomas. PMID- 27401889 TI - Cancer Control in Central and Eastern Europe. PMID- 27401890 TI - Cancer Control in Central and Eastern Europe: Current Situation and Recommendations for Improvement. AB - : : The incidence of many cancers is higher in Western European (WE) countries, but mortality is frequently higher in Central and Eastern European (CEE) countries. A panel of oncology leaders from CEE countries participating in the South Eastern European Research Oncology Group (SEEROG) was formed in 2015, aiming to analyze the current status and trends of oncology care in CEE and to propose recommendations leading to improved care and outcomes. The SEEROG panel, meeting during the 11th Central European Oncology Congress, proposed the following: (a) national cancer control plans (NCCPs) required in all CEE countries, defining priorities in cancer care, including finance allocation considering limited health care budgets; (b) national cancer registries, describing in detail epidemiological trends; (c) efforts to strengthen comprehensive cancer centers; (d) that multidisciplinary care should be mandated by the NCCPs; (e) that smaller hospitals should be connected to multidisciplinary tumor boards via the Internet, providing access to specialized expertise; (f) nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption and centrally evaluated secondary prevention programs for cervical, colorectal, and breast cancers; (g) prioritize education for all involved in cancer care, including oncology nurses, general practitioners, and palliative care providers; (h) establish outpatient care in day hospitals to reduce costs associated with the current inpatient model of care in CEE countries and to improve patients' quality of life; (i) long-term pharmacoeconomic evaluations of new therapies in CEE countries; (j) increase national oncology budgets in view of the higher mortality rates in CEE compared with WE countries; and (k) CEE countries urgently need help from the European Union to increase and monitor overall investment in cancer care. IMPLICATIONS FOR PRACTICE: Significant differences in cancer incidence and mortality have been observed between European countries. While the incidence of many cancer types is higher in Western European (WE) countries, the mortality is generally higher in Central and Eastern Europe (CEE). The primary purpose of this review was to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians, regulators, and payers, and to propose the most needed changes in order to make the oncology care in CEE closer to the WE standards. PMID- 27401891 TI - Sarcomas Associated With Genetic Cancer Predisposition Syndromes: A Review. AB - : Sarcomas are rare mesenchymal malignancies that demonstrate great clinical and biological heterogeneity. A variety of sarcomas develop in the context of well defined heritable cancer predisposition syndromes, associations that are often overlooked, given the rarity and diversity of sarcomas and the equivalent relative infrequency of cancer genetic syndromes. This review describes in detail selected heritable cancer predisposition syndromes that are known to be associated with sarcomas. Beyond the molecular and clinical features that define each syndrome, disparities in clinical presentation, natural history, and treatment of syndrome-associated compared with otherwise histologically identical sporadic sarcomas will be described. The clinical approach to selected sarcoma subsets with a view to identifying possible associations with these syndromes will then be described. Although the treatment of the majority of sarcomas will not differ significantly between sporadic cases and those associated with predisposition syndromes, knowledge of features such as unique anatomic sites of affliction or excess toxicities with particular cytotoxic therapies can facilitate alterations in therapeutic strategies to maximize efficacy and minimize toxicity. In addition, recognition of cancer genetic predisposition syndrome will allow patients and their relatives to undertake appropriate genetic counseling and testing, as well as screening, surveillance, and interventional measures, as needed. Situating sarcomas within the genetic endowment of particular patients-specifically that which confers a higher risk of malignancy will enable clinicians to better manage the patient as a whole, complementing the great efforts currently routinely undertaken to genomically characterize somatic tumor changes with a view to achieving the dream of personalized medicine. IMPLICATIONS FOR PRACTICE: Sarcomas are uncommon malignancies that often occur sporadically but can also arise in the setting of a recognized heritable cancer predisposition syndrome. Identification of such associations when present can facilitate refinement and optimization of treatment strategies for the sarcoma so as to minimize toxicity and maximize efficacy. Discerning genetic predisposition can also facilitate institution of genetic counseling, as well as screening or surveillance schema for both the patient and his or her relatives, if required. Vigilance for these syndromes has the potential to significantly enhance the quality and comprehensiveness of sarcoma clinical management. PMID- 27401892 TI - A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction. AB - BACKGROUND: The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined. PATIENTS AND METHODS: Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles, followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and 0.60 in the MET-positive population. Secondary endpoints were overall survival (OS), overall response rate (ORR), and safety. RESULTS: Overall, 123 patients were enrolled (n = 62 onartuzumab, n = 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95% confidence interval [CI], 0.71-1.63; p = .71). In the MET-positive population, median PFS was 5.95 versus 6.80 months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60-3.20; p = .45). Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64-1.75; p = .83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45-2.78; p = .80). ORR was 60.5% for the onartuzumab group and 57.1% for placebo. Grade 3-5 adverse events (AEs) were seen in 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively. CONCLUSION: The addition of onartuzumab to mFOLFOX6 in gastric cancer did not improve efficacy in an unselected population or in a MET immunohistochemistry positive population. IMPLICATIONS FOR PRACTICE: The YO28252 study demonstrated that the addition of the anti-MET agent onartuzumab to mFOLFOX6 for treatment of gastric cancer did not improve efficacy in an overall study population or those selected for positive MET status by immunohistochemistry. This highlights the importance of correctly selecting biomarkers for targeted therapies. A multivariate analysis suggested that MET positivity may still be prognostic for worse median overall survival in gastric cancer; therefore, it is important to continue investigation into the optimal approach to inhibit MET signaling in gastric cancer. PMID- 27401893 TI - Thinking Systematically About the Off-Label Use of Cancer Drugs and Combinations for Patients Who Have Exhausted Proven Therapies. PMID- 27401894 TI - Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. AB - : : Immune checkpoint inhibitors have emerged as a mainstay of melanoma therapy and are playing an increasingly important role in the treatment of other tumor types. The clinical benefit afforded by these treatments can be accompanied by a unique spectrum of adverse events, called immune-related adverse events (irAEs), which reflect the drug's immune-based mechanism of action. IrAEs typically originate in the skin, gastrointestinal tract, liver, and endocrine system, although other organ systems may also be affected. This article provides an overview of irAEs associated with anti-programmed death-1 (anti-PD-1) antibodies (nivolumab and pembrolizumab) as monotherapy or in combination with anti cytotoxic T-lymphocyte antigen-4 inhibition (ipilimumab), followed by a discussion of irAEs of special clinical interest based on the potential for morbidity, frequent steroid use, and inpatient admission. We review clinical trial data and provide recommendations on how to manage irAEs associated with anti-PD-1 agents based on clinical experience and established management guidelines. We further illustrate the practical considerations of managing irAEs by presenting three cases of immune-related toxicity in melanoma patients treated with nivolumab or pembrolizumab. A better understanding of the identification and management of irAEs will help inform health care providers about the risks associated with anti-PD-1 treatment, to ensure the safe and appropriate use of these important new treatments. IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitors have demonstrated significant clinical benefit in advanced melanoma and other tumor types. These treatments are associated with immune-related adverse events (irAEs), which most commonly affect the skin and gastrointestinal tract, and, to a lesser extent, the liver, endocrine system, and other organs. This review focuses on the management of irAEs after treatment with anti programmed death-1 (anti-PD-1) antibodies (nivolumab or pembrolizumab) as monotherapy or in combination with anti-cytotoxic T-lymphocyte antigen-4 inhibition (ipilimumab) in patients with advanced melanoma. A better understanding of the management of irAEs will help ensure the safe and appropriate use of anti-PD-1 agents in melanoma and other tumor types. PMID- 27401895 TI - Gastroenteropancreatic Well-Differentiated Grade 3 Neuroendocrine Tumors: Review and Position Statement. AB - : : In 2010, the World Health Organization (WHO) classification of neuroendocrine neoplasms was reviewed and validated the crucial role of the proliferative rate. According to the WHO classification 2010, gastroenteropancreatic neuroendocrine neoplasms are classified as well-differentiated neuroendocrine tumors (NETs) of grade 1 or 2 in up to 84%, or poorly differentiated neuroendocrine carcinomas in 6%-8%. Neuroendocrine carcinomas are of grade G. Recently, a proportion of neuroendocrine tumors presenting a number of mitoses or a Ki-67 index higher than 20% and a well-differentiated morphology have been identified, calling for a new category, well-differentiated grade 3 NET (NET G-3). Studies that have reported the characteristics of neuroendocrine neoplasms have identified more well differentiated NET G-3 than neuroendocrine carcinomas. The main localizations of NET G-3 are the pancreas, stomach, and colon. Treatment for NET G-3 is not standardized and is balanced between G-1/2 neuroendocrine tumor and neuroendocrine carcinoma treatments. In nonmetastatic neuroendocrine tumors, the European and American guidelines recommended a surgical resection for localized neuroendocrine neoplasm, irrespective of the tumor grading. In NET G-3, chemotherapy is the benchmark if the main treatment goal is reduction of the tumor mass, particularly if it would allow a secondary surgery. In the present work, we review the epidemiology and make recommendations for the management of NET G-3. IMPLICATIONS FOR PRACTICE: Neuroendocrine tumors presenting a number of mitoses or a Ki-67 index higher than 20% and a well-differentiated morphology have been identified and named well-differentiated grade 3 neuroendocrine tumors (NET G-3). The main localizations of NET G-3 are the pancreas, stomach, and colon. The prognosis is worse than that for NET G-2. In nonmetastatic NET G-3, surgery appeared to be the first option. The chemotherapy regimen in pancreatic NET G-3 should be in line with that implemented in NET G-1/2 when the Ki-67 index is below 55% and should be in line with that implemented for neuroendocrine carcinoma when Ki-67 is above 55%. PMID- 27401896 TI - Impact on Patient Management of [18F]-Fluorodeoxyglucose-Positron Emission Tomography (PET) Used for Cancer Diagnosis: Analysis of Data From the National Oncologic PET Registry. AB - INTRODUCTION: We assessed the impact of [(18)F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) on intended management of patients in the National Oncologic PET Registry (NOPR) for three different diagnostic indications: (a) determining whether a suspicious lesion is cancer (Dx), (b) detecting an unknown primary tumor site when there is confirmed or strongly suspected metastatic disease (cancer of unknown primary origin [CUP]), and (c) detecting a primary tumor site when there is a presumed paraneoplastic syndrome (PNS). METHODS: We reviewed a sample of randomly selected reports of NOPR subjects who underwent PET for Dx and CUP and all reports for PNS to find subjects for analysis. For these studies, we evaluated the impact of PET on referring physicians' intended management, based on their management plans reported before and after PET. RESULTS: Intended management was changed more frequently in the CUP group (43.1%) than in the Dx (23.9%) and PNS (25.4%) groups (CUP vs. Dx, p < .0001; PNS vs. Dx, p < .0001; CUP vs. PNS, p < .0002). Referring physicians reported that, in light of PET results, they were able to avoid further testing in approximately three fourths of patients (71.8%-74.6%). At the time when the post-PET forms were completed, biopsies of suspicious sites had been performed in 21.2%, 32.4%, and 23.2%, respectively, of Dx, CUP, and PNS cases. CONCLUSION: Our analysis of NOPR data shows that PET appears to have a substantial impact on intended management when used for three common diagnostic indications. IMPLICATIONS FOR PRACTICE: [(18)F]-fluorodeoxyglucose-positron emission tomography appears to have a substantial impact on intended management when used for three targeted diagnostic indications: (a) determining whether a suspicious lesion is cancer, (b) detecting an unknown primary tumor site in a patient with confirmed or strongly suspected metastatic disease, and (c) detecting a primary tumor site in a patient with a presumed paraneoplastic syndrome. PMID- 27401897 TI - FDG-PET/CT and MRI for Evaluation of Pathologic Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer: A Meta-Analysis of Diagnostic Accuracy Studies. AB - INTRODUCTION: This study compared the diagnostic test accuracy of magnetic resonance imaging (MRI) with that of (18)F-fluoro-2-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging in assessment of response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: A systematic search was performed in PubMed and EMBASE (last updated in June 2015). Studies investigating the performance of MRI and FDG-PET or FDG-PET/CT imaging during or after completion of NAC in patients with histologically proven breast cancer were eligible for inclusion. We considered only studies reporting a direct comparison between these imaging modalities to establish precise summary estimates in the same setting of patients. Pathologic response was considered as the reference standard. Two authors independently screened and selected studies that met the inclusion criteria and extracted the data. RESULTS: A total of 10 studies were included. The pooled estimates of sensitivity and specificity across all included studies were 0.71 and 0.77 for FDG-PET/CT (n = 535) and 0.88 and 0.55 for MRI (n = 492), respectively. Studies were subgrouped according to the time of therapy assessment. In the intra-NAC setting, FDG-PET/CT imaging outperformed MRI with fairly similar pooled sensitivity (0.91 vs. 0.89) and higher specificity (0.69 vs. 0.42). However, MRI appeared to have higher diagnostic accuracy than FDG PET/CT imaging when performed after the completion of NAC, with significantly higher sensitivity (0.88 vs. 0.57). CONCLUSION: Analysis of the available studies of patients with breast cancer indicates that the timing of imaging for NAC response assessment exerts a major influence on the estimates of diagnostic accuracy. FDG-PET/CT imaging outperformed MRI in intra-NAC assessment, whereas the overall performance of MRI was higher after completion of NAC, before surgery. IMPLICATIONS FOR PRACTICE: The timing of therapy assessment imaging exerts a major influence on overall estimates of diagnostic accuracy. (18)F fluoro-2-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) imaging outperformed magnetic resonance imaging (MRI) in intra-neoadjuvant chemotherapy assessment with fairly similar pooled sensitivity and higher specificity. However, MRI appeared to be more accurate than FDG-PET/CT in predicting pathologic response when used in the post-therapy setting. PMID- 27401898 TI - Breast Camps for Awareness and Early Diagnosis of Breast Cancer in Countries With Limited Resources: A Multidisciplinary Model From Kenya. AB - BACKGROUND: Breast cancer is the most common cancer of women in Kenya. There are no national breast cancer early diagnosis programs in Kenya. OBJECTIVE: The objective was to conduct a pilot breast cancer awareness and diagnosis program at three different types of facilities in Kenya. METHODS: This program was conducted at a not-for-profit private hospital, a faith-based public hospital, and a government public referral hospital. Women aged 15 years and older were invited. Demographic, risk factor, knowledge, attitudes, and screening practice data were collected. Breast health information was delivered, and clinical breast examinations (CBEs) were performed. When appropriate, ultrasound imaging, fine needle aspirate (FNA) diagnoses, core biopsies, and onward referrals were provided. RESULTS: A total of 1,094 women were enrolled in the three breast camps. Of those, 56% knew the symptoms and signs of breast cancer, 44% knew how breast cancer was diagnosed, 37% performed regular breast self-exams, and 7% had a mammogram or breast ultrasound in the past year. Of the 1,094 women enrolled, 246 (23%) had previously noticed a lump in their breast. A total of 157 participants (14%) had abnormal CBEs, of whom 111 had ultrasound exams, 65 had FNAs, and 18 had core biopsies. A total of 14 invasive breast cancers and 1 malignant phyllodes tumor were diagnosed CONCLUSION: Conducting a multidisciplinary breast camp awareness and early diagnosis program is feasible in different types of health facilities within a low- and middle-income country setting. This can be a model for breast cancer awareness and point-of-care diagnosis in countries with limited resources like Kenya. IMPLICATIONS FOR PRACTICE: This work describes a novel breast cancer awareness and early diagnosis demonstration program in a low- and middle-income country within a limited resource setting. The program includes breast self-awareness and breast cancer education, clinical exams, and point-of-care diagnostics for women in three different types of health facilities in Kenya. This pilot program has the potential of being replicated on a national scale to create awareness about breast cancer and downstage its presentation. PMID- 27401900 TI - Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 66, part 3, of the IJSEM. AB - This listing of names of prokaryotes published in a previous issue of the IJSEM is provided as a service to bacteriology to assist in the recognition of new names and new combinations. This procedure was proposed by the Judicial Commission [Minute 11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are listed according to the Rules of priority (i.e. page number and order of valid publication of names in the original articles). PMID- 27401899 TI - Parental separation: a risk for the psychomotor development of children aged 28 to 32 months? A cross-sectional study. AB - BACKGROUND: In Western countries, about a quarter of children are affected by parental separation and a number of authors have previously investigated how familial structure impacts children's health. The purpose of the work: to analyze the psychomotor development of children aged 28 to 32 months based on family structure (parents together or separated), independently of the influence of socio-economic environment that is well documented. To analyse the psychomotor development of children younger than 3 years based on family structure (parents together or separated) independently of the influence of socio-economic environment that is well documented. METHODS: Cross-sectional study by examination of 28 871 children as part of a free preventive medicine consultation. The data came from an assessment conducted 28 to 32 months after birth during which information was collected about the psychomotor development: to perform a standing jump, dress themselves, draw a vertical line and circle, use the "I" pronoun, build a three-word sentence, and say their first name RESULTS: Ten percent of the children had separated parents. Compared to parents who were together, when adjusting for the socioeconomic environment, as well as all potential confounders, the adjusted odds ratios (ORs) (95 % confidence interval [CI]) for children with separated parents, in terms of their ability to perform a standing jump, dress themselves, and draw a vertical line and circle were respectively 0.9 (0.7-1.1), 1.1 (0.9-1.2), 1.3 (1.1-1.4) and 1.2 (1.1-1.4). The adjusted ORs (95 % CI) for children's inability to say the "I" pronoun, build a three-word sentence, and say their first name were respectively 1.2 (1.1-1.3), 1.3 (1.2-1.5), and 1.2 (0.9-1.5). CONCLUSIONS: After adjusting for sociocultural factors and other potential confounders, we observed that the children exhibited slower progression in psychomotor development, especially in language and graphic abilities when their parents were separated. While the implications of our study are somewhat limited, they do provide us with the necessary arguments enabling us to set up a prospective cohort study. Such a study should be able to better assess the impact of parental separation on the child's development, confirming our preliminary results. PMID- 27401901 TI - Dexamphetamine and the faltering war against depression and suicide. PMID- 27401902 TI - The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness. AB - BACKGROUND: It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment. OBJECTIVES: To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness. DESIGN: Multicentre, prospective diagnostic cohort study. SETTING AND PARTICIPANTS: Children < 5 years old presenting to primary care with an acute illness and/or new urinary symptoms. METHODS: One hundred and seven clinical characteristics (index tests) were recorded from the child's past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood ('clinical diagnosis') and urine sampling and treatment intentions ('clinical judgement') were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at >= 10(5) colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the 'clinician diagnosis' AUROC. Decision-analytic models were used to identify optimal urine sampling strategy compared with 'clinical judgement'. RESULTS: A total of 7163 children were recruited, of whom 50% were female and 49% were < 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were >= 2 years old, with 2.2% meeting the UTI definition. Among these, 'clinical diagnosis' correctly identified 46.6% of positive cultures, with 94.7% specificity and an AUROC of 0.77 (95% CI 0.71 to 0.83). Four symptoms, three signs and three dipstick results were independently associated with UTI with an AUROC (95% CI; bootstrap-validated AUROC) of 0.89 (0.85 to 0.95; validated 0.88) for symptoms and signs, increasing to 0.93 (0.90 to 0.97; validated 0.90) with dipstick results. Nappy pad samples were provided from the other 2277 children, of whom 82% were < 2 years old and 1.3% met the UTI definition. 'Clinical diagnosis' correctly identified 13.3% positive cultures, with 98.5% specificity and an AUROC of 0.63 (95% CI 0.53 to 0.72). Four symptoms and two dipstick results were independently associated with UTI, with an AUROC of 0.81 (0.72 to 0.90; validated 0.78) for symptoms, increasing to 0.87 (0.80 to 0.94; validated 0.82) with the dipstick findings. A high specificity threshold for the clean catch model was more accurate and less costly than, and as effective as, clinical judgement. The additional diagnostic utility of dipstick testing was offset by its costs. The cost-effectiveness of the nappy pad model was not clear-cut. CONCLUSIONS: Clinicians should prioritise the use of clean-catch sampling as symptoms and signs can cost-effectively improve the identification of UTI in young children where clean catch is possible. Dipstick testing can improve targeting of antibiotic treatment, but at a higher cost than waiting for a laboratory result. Future research is needed to distinguish pathogens from contaminants, assess the impact of the clean-catch algorithm on patient outcomes, and the cost-effectiveness of presumptive versus dipstick versus laboratory guided antibiotic treatment. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 27401904 TI - Does a learned journal require regular re-vamping? PMID- 27401903 TI - mTOR inhibition attenuates glucose deprivation-induced death in photoreceptors via suppressing a mitochondria-dependent apoptotic pathway. AB - Acute energy depletion contributes to ischemia-induced retinal neuronal injury, causing photoreceptor death and subsequent vision loss. The mTOR pathway is a crucial cellular signaling hub modulating RNA transcription, protein synthesis, and metabolic balance. Thus, we mimicked acute energy depletion in photoreceptor cells (661W cells) with glucose deprivation and investigated neuroprotective mechanisms of mTOR inhibition. We found that treatment with rapamycin, an mTOR specific inhibitor, reduced intracellular ROS, maintained the mitochondrial membrane potential and restored mitochondrial dysfunction. In addition, inhibiting the mTOR signal suppressed DRP1 translocation to the mitochondria, pro apoptotic mitochondrial protein release, and caspase 3 activation when glucose was deprived. Inhibition of mTOR offers significant neuroprotection against glucose deprivation-induced injury in 661W cells, chiefly via suppressing mitochondrial-dependent pathways. These observations may shed light on treating ischemia-related retinal diseases. PMID- 27401905 TI - Risk factors and clinical outcomes for carbapenem-resistant Enterobacteriaceae nosocomial infections. AB - This study was aimed to determine the risk factors of Carbapenem-resistant Enterobacteriaceae (CRE) nosocomial infections and assess the clinical outcomes. A case-case-control design was used to compare two groups of case patients with control patients from March 2010 to November 2014 in China. Risk factors for the acquisition of CRE infections and clinical outcomes were analyzed by univariable and multivariable analysis. A total of 94 patients with CRE infections, 93 patients with Carbapenem-susceptible Enterobacteriaceae (CSE) infections, and 93 patients with organisms other than Enterobacteriaceae infections were enrolled in this study. Fifty-five isolates were detected as the carbapenemase gene. KPC-2 was the most common carbapenemase (65.5 %, 36/55), followed by NDM-1 (16.4 %, 9/55), IMP-4 (14.5 %, 8/55), NDM-5 (1.8 %, 1/55), and NDM-7 (1.8 %, 1/55). Multivariable analysis implicated previous use of third or fourth generation cephalosporins (odds ratio [OR], 4.557; 95 % confidence interval [CI], 1.971 10.539; P < 0.001) and carbapenems (OR, 4.058; 95 % CI, 1.753-9.397; P = 0.001) as independent risk factors associated with CRE infection. The in-hospital mortality of the CRE group was 57.4 %. In the population of CRE infection, presence of central venous catheters (OR, 4.464; 95 % CI, 1.332-14.925; P = 0.015) and receipt of immunosuppressors (OR, 7.246; 95 % CI, 1.217-43.478; P = 0.030) were independent risk factors for mortality. Appropriate definitive treatment (OR, 0.339; 95 % CI, 0.120-0.954; P = 0.040) was a protective factor for in-hospital death of CRE infection. Kaplan-Meier curves of the CRE group had the shortest survival time compared with the other two groups. Survival time of patients infected with Enterobacteriaceae with a high meropenem MIC (>=8 mg/L) was shorter than that of patients with a low meropenem MIC (2,4, and <= 1 mg/L). In conclusion, CRE nosocomial infections are associated with prior exposure to third or fourth generation cephalosporins and carbapenems. Patients infected with CRE had poor outcome and high mortality, especially high meropenem MIC (>=8 mg/L). Appropriate definitive treatment to CRE infections in the patient is essential. PMID- 27401906 TI - Distribution of common pathogens in patients with pyogenic liver abscess in China: a meta-analysis. AB - Pyogenic liver abscess (PLA) is a potentially life-threatening disease in many parts of the world, especially in Asia. The aim of this study was to quantify the proportion of common pathogens in patients with PLA in China, using a meta analysis method based on systematic review of published studies. Several electronic databases were searched to identify the studies reporting the pathogens of PLA. We performed a meta-analysis to calculate the pooled proportion of pathogens and subgroup analysis among the included studies using R 3.1.1 software. In total, 183 studies were included in our final analysis, Klebsiella spp (54 %), Escherichia spp (29 %), Enterobacter spp (9 %), Proteus spp (6 %) and Pseudomonas spp (5 %) comprised the major gram-negative bacteria. Gram-positive bacteria mainly included Staphylococcus spp (13 %), Streptococcus spp (8 %) and Enterococcus spp (7 %). The distribution of pathogens in PLA patients were different in different economic regions in China. The proportion of Klebsiella spp had an upward tendency in recent years compared to other pathogens. In addition, the proportion of common pathogens in PLA patients with diabetes mellitus (DM) were carried out indicating that the dominant pathogens were Klebsiella spp (66 %), Escherichia spp (21 %) and Enterobacter spp (11 %). This meta-analysis showed that the main pathogens of PLA were Klebsiella spp, Escherichia spp, Staphylococcus spp, and Enterobacter spp in China. To ensure a precise estimate of the epidemiology of the pathogens, further large-scale or even a population-based study is needed. PMID- 27401908 TI - Harnessing Topographical Cues for Tissue Engineering. PMID- 27401907 TI - Expression of inflammation-related genes in the lung of BALB/c mice response to H7N9 influenza A virus with different pathogenicity. AB - H7N9 influenza A virus (IAV)-infected human cases are increasing and reported over 200 mortalities since its first emergence in 2013. Host inflammatory response contributes to the clearance of influenza virus; meanwhile, the induced "cytokine storm" also leads to pathological lesions. However, what inflammation related response of the host for H7N9 influenza A virus infection to survival from injures of exuberant cytokine release is still obscure. In this research, expression pattern and histological distribution of inflammation-related genes, RIP3, NLRP3, IL-1beta, TNF-alpha, Slit2 and Robo4 in the lung of BALB/c mice infected with two H7N9 IAV strains with only a PB2 residue 627 difference were investigated, as well as the histopathological injury of the lung. Results showed that significantly higher expression level of NLRP3, RIP3, IL-1beta and TNF-alpha in H7N9-infected groups compared with the control would play a key role in driving lung pathological lesion. While the expression level of Slit2 and Robo4 in H7N9 rVK627E group had significantly increased trend than VK627 which might be the main factor to inhibit the interstitial pneumonia and infiltration. Also, H7N9 induced the histopathological changes in the lung of infected mice, and RIP3, NLRP3, IL-1beta, TNF-alpha, Slit2 and Robo4 showed cell-specific distribution in the lung. The results will provide basic data for further research on the mechanism of inflammatory response and understanding of the role of site 627 in PB2 in H7N9 IAVs infection. In addition, enhancing the resilience of the host vascular system to the inflammatory response by regulation of Slit2 Robo4 signaling pathway might provide a novel strategy for H7N9 IAVs infection. PMID- 27401909 TI - Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. AB - BACKGROUND: Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. METHODS: This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-alpha). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. RESULTS: A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. CONCLUSION: Interleukin-6 appears to be implicated in the development of chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. It may become a potential target in the prevention and early treatment of diabetes after diseases of the exocrine pancreas. PMID- 27401910 TI - Reduced crown root number improves water acquisition under water deficit stress in maize (Zea mays L.). AB - In this study we test the hypothesis that maize genotypes with reduced crown root number (CN) will have greater root depth and improved water acquisition from drying soil. Maize recombinant inbred lines with contrasting CN were evaluated under water stress in greenhouse mesocosms and field rainout shelters. CN varied from 25 to 62 among genotypes. Under water stress in the mesocosms, genotypes with low CN had 31% fewer crown roots, 30% deeper rooting, 56% greater stomatal conductance, 45% greater leaf CO2 assimilation, 61% net canopy CO2 assimilation, and 55% greater shoot biomass than genotypes with high CN at 35 days after planting. Under water stress in the field, genotypes with low CN had 21% fewer crown roots, 41% deeper rooting, 48% lighter stem water oxygen isotope enrichment (delta(18)O) signature signifying deeper water capture, 13% greater leaf relative water content, 33% greater shoot biomass at anthesis, and 57% greater yield than genotypes with high CN. These results support the hypothesis that low CN improves drought tolerance by increasing rooting depth and water acquisition from the subsoil. PMID- 27401911 TI - Older Thinopyrum intermedium (Poaceae) plants exhibit superior photosynthetic tolerance to cold stress and greater increases in two photosynthetic enzymes under freezing stress compared with young plants. AB - Effects of plant age on resource acquisition and stress tolerance processes is a largely unstudied subject in herbaceous perennials. In a field experiment, we compared rates of photosynthesis (A), ribulose-1,5-bisphosphate (RuBP) carboxylation capacity (V Cmax), maximum electron transport rate (J max), and triose phosphate utilization (TPU), as well as concentrations of Rubisco and sucrose-phosphate synthase (SPS) in 5-year-old and 2-year-old intermediate wheatgrass (Thinopyrum intermedium) under both optimal growing conditions and cold stress in early spring and autumn. This species is a relative of wheat undergoing domestication. An additional experiment compared photosynthetic rates in different cohorts at mid-season and under colder conditions. We hypothesized that photosynthetic capacity in older plants would be lower under favorable conditions but higher under cold stress. Our hypothesis was generally supported. Under cold stress, 5-year-old plants exhibited higher A, TPU, and temperature adjusted V Cmax than younger plants, as well as 50% more SPS and 37% more Rubisco. In contrast, at mid-season, photosynthetic capacities in older plants were lower than in younger plants in one experiment, and similar in the other, independent of differences in water status. Both cohorts increased A, temperature adjusted TPU and J max, [Rubisco], and [SPS] under cold stress, but changes were greater in older plants. Photosynthetic differences were largest at 1.2 oC in very early spring, where older plants had 200% higher A and maintained up to 17% of their peak photosynthetic capacity. We find evidence of increased cold tolerance in older cohorts of wheatgrass, consistent with a growing body of research in woody perennials. PMID- 27401912 TI - Hormone-controlled UV-B responses in plants. AB - Ultraviolet B (UV-B) light is a portion of solar radiation that has significant effects on the development and metabolism of plants. Effects of UV-B on plants can be classified into photomorphogenic effects and stress effects. These effects largely rely on the control of, and interactions with, hormonal pathways. The fairly recent discovery of the UV-B-specific photoreceptor UV RESISTANCE LOCUS 8 (UVR8) allowed evaluation of the role of downstream hormones, leading to the identification of connections with auxin and gibberellin. Moreover, a substantial overlap between UVR8 and phytochrome responses has been shown, suggesting that part of the responses caused by UVR8 are under PHYTOCHROME INTERACTING FACTOR control. UV-B effects can also be independent of UVR8, and affect different hormonal pathways. UV-B affects hormonal pathways in various ways: photochemically, affecting biosynthesis, transport, and/or signaling. This review concludes that the effects of UV-B on hormonal regulation can be roughly divided in two: inhibition of growth-promoting hormones; and the enhancement of environmental stress-induced defense hormones. PMID- 27401914 TI - Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites. AB - 1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl 5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. 4. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6 methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6 methylenedioxy-2-aminoindane. 5. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2 aminoindane was supported by synthesised reference standards. PMID- 27401913 TI - Immune Gamma Globulin Therapeutic Indications in Immune Deficiency and Autoimmunity. AB - Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness. PMID- 27401915 TI - Age is not associated with intracranial haemorrhage in patients with mild traumatic brain injury and oral anticoagulation. AB - BACKGROUND: Patients admitted to emergency departments with traumatic brain injury (TBI) are commonly being treated with oral anticoagulants. In contrast to patients without anticoagulant medication, no guidelines, scores or recommendations exist for the management of mild traumatic brain injury in these patients. We therefore tested whether age as one of the high risk factors of the Canadian head CT rule is applicable to a patient population on oral anticoagulants. METHODS: This cross-sectional analysis included all patients with mild TBI and concomitant oral anticoagulant therapy admitted to the Emergency Department, Inselspital Bern, Switzerland, from November 2009 to October 2014 (n = 200). Using a logistic regression model, two groups of patients with mild TBI on oral anticoagulant therapy were compared - those with and those without intracranial haemorrhage. RESULTS: There was no significant difference in age between the patient groups with (n = 86) and without (n = 114) intracranial haemorrhage (p = 0.078). In univariate logistic regression, GCS (OR = 0.419 (0.258; 0.680)) and thromboembolic event as reason for anticoagulant therapy (OR = 0.486 (0.257; 0.918)) were significantly associated with intracranial haemorrhage in patients with mild TBI and anticoagulation (all p < 0.05). However, there was no association with age (p = 0.078, OR = 1.024 (0.997; 1.051)), the type of accident or additional medication with acetylsalicylic acid or clopidogrel ((both p > 0.05; 0.552 (0.139; 2.202) and 0.256 (0.029; 2.237), respectively). CONCLUSION: Our study found no association between age and intracranial bleeding. Therefore, until further risk factors are identified, diagnostic imaging with CCT remains necessary for mild TBI patients on oral anticoagulation of all ages, especially those with therapeutic anticoagulation because of thromboembolic events. PMID- 27401917 TI - Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro. AB - BACKGROUND: Chinese licorice, (Glycyrrhiza uralensis Fisch.) is one of the commonly prescribed herbs in Traditional Chinese Medicine (TCM). Gancao, as commonly known in China, is associated with immune-modulating and anti-tumor potential though the mechanism of action is not well known. In this study, we investigated the in vitro immunomodulatory and antitumor potential of Glycyrrhiza uralensis polysaccharides fractions of high molecular weight (fraction A), low molecular weight (fraction B) and crude extract (fraction C). METHODS: Cell proliferation and cytotoxicity was investigated using Cell Counting kit 8 (CCK-8) on Intestinal epithelial cell line (IEC-6) and Colon carcinoma cell line (CT-26). IL-7 gene expression relative to GAPDH was analysed using Real time PCR. The stimulation and viability of T lymphocytes was determined by Trypan blue exclusion assay. RESULTS: G.uralensis polysaccharides did not inhibit proliferation of IEC-6 cells even at high concentration. The ED50 was found to be 100 MUg/ml. On the other hand, the polysaccharides inhibited the proliferation of cancer cells (CT-26) at a concentration of <=50 MUg/ml. Within 72 h of treatment with the polysaccharides, expression of IL-7 gene was up-regulated over 2 times. It was also noted that, IEC-6 cells secrete IL-7 cytokine into media when treated with G.uralensis polysaccharides. The secreted IL-7 stimulated proliferation of freshly isolated T lymphocytes within 6 h. The effect of the polysaccharides were found to be molecular weight depended, with low molecular weight having a profound effect compared to high molecular weight and total crude extract. CONCLUSION: Our findings indicate that G.uralensis polysaccharides especially those of low molecular weight have a potential as anticancer agents. Of great importance, is the ability of the polysaccharides to up-regulate anticancer cytokine IL-7, which is important in proliferation and maturation of immune cells and it is associated with better prognosis in cancer. Therefore, immunomodulation is a possible mode of action of the polysaccharides in cancer therapy. PMID- 27401918 TI - Arsenic exposure and risk of preeclampsia in a Mexican mestizo population. AB - BACKGROUND: Exposure to arsenic in drinking water has been associated with various complications of pregnancy including fetal loss, low birth weight, anemia, gestational diabetes and spontaneous abortion. However, to date, there are no studies evaluating its possible association with preeclampsia. METHODS: This case-control study involved 104 preeclamptic and 202 healthy pregnant women. The concentrations of arsenic in drinking water and urine were measured using a Microwave Plasma-Atomic Emission Spectrometer. RESULTS: We found relatively low levels of arsenic in household tap water (range of 2.48-76.02 MUg/L) and in the urine of the participants (7.1 MUg/L vs 6.78 MUg/L in cases and controls, respectively). CONCLUSIONS: The analysis between groups showed for the first time that at these lower levels of exposure there is no association with preeclampsia. PMID- 27401920 TI - The use of a cutting balloon in contemporary reverse controlled antegrade and retrograde subintimal tracking (reverse CART) technique. AB - The key concept of reverse controlled antegrade and retrograde tracking (CART) technique is retrograde puncture with a tapered wire to an antegrade balloon (contemporary reverse CART) or new connections between the antegrade and retrograde subintimal space (classical reverse CART). In our case, a 75-year-old man with severe chronic total occlusion of the right coronary artery, reverse CART with conventional balloons could not be accomplished. Externalization wiring was completed by contemporary reverse CART using a cutting balloon as an antegrade balloon to improve the fenestration force of the retrograde guidewire. Thus, the use of a cutting balloon for contemporary reverse CART might be promising. PMID- 27401919 TI - Mutation Drivers of Immunological Responses to Cancer. AB - In cancer immunology, somatic missense mutations have been mostly studied with regard to their role in the generation of neoantigens. However, growing evidence suggests that mutations in certain genes, such as CASP8 or TP53, influence the immune response against a tumor by other mechanisms. Identifying these genes and mechanisms is important because, just as the identification of cancer driver genes led to the development of personalized cancer therapies, a comprehensive catalog of such cancer immunity drivers will aid in the development of therapies aimed at restoring antitumor immunity. Here, we present an algorithm, domainXplorer, that can be used to identify potential cancer immunity drivers. To demonstrate its potential, we used it to analyze a dataset of 5,164 tumor samples from The Cancer Genome Atlas (TCGA) and to identify protein domains in which mutation status correlates with the presence of immune cells in cancer tissue (immune infiltrate). We identified 122 such protein regions, including several that belong to proteins with known roles in immune response, such as C2, CD163L1, or FCgammaR2A. In several cases, we show that mutations within the same protein can be associated with more or less immune cell infiltration, depending on the specific domain mutated. These results expand the catalog of potential cancer immunity drivers and highlight the importance of taking into account the structural context of somatic mutations when analyzing their potential association with immune phenotypes. Cancer Immunol Res; 4(9); 789-98. (c)2016 AACR. PMID- 27401921 TI - Comparison of intramuscular alfaxalone and ketamine combined with dexmedetomidine and butorphanol for castration in cats. AB - Objectives Cardiorespiratory parameters and anaesthesia quality in cats anaesthetised with either intramuscular (IM) alfaxalone or ketamine both combined with dexmedetomidine and butorphanol for castration were evaluated. Methods Thirty-two client-owned cats were randomly assigned to receive either alfaxalone (A; 3 mg/kg IM) or ketamine (K; 5 mg/kg IM), combined with dexmedetomidine (10 MUg/kg) and butorphanol (0.2 mg/kg). Heart rate (HR), respiratory rate (RR) and rectal temperature (T degrees ) were recorded prior to drug administration. Pulse rate (PR) and RR were recorded 10 (T10) and 15 (T15) mins after injection (T0). Cardiorespiratory values (PR, RR, SPO2, blood pressure, PE'CO2) were recorded every 5 mins for the duration of the procedure. Pain at injection, intubation and recovery were evaluated with simple descriptive scores. Feasibility of anaesthesia was evaluated by the number of top-ups of anaesthetic needed. Cat attitude, ability to walk and presence of ataxia were assessed several times after extubation (Texmin) and the time between injection and extubation recorded. Pain was assessed at Tex120 and Tex240 with the 4Avet-pain score. Results The RR was significantly lower in group K at T10 (RRK = 28 +/-13.35 breaths per minute [brpm], RRA= 43.24 +/-7.04 brpm) and T15 (RRK = 28 +/-11.53 brpm vs RRA = 43 +/ 12.18 brpm). Time to extubation was significantly longer in group A (TA = 62 +/ 14.6 mins, TK = 45.13 +/- 7.38 mins). Cats in group K needed more top-ups, were more ataxic at Tex120, had a worse recovery score at Tex60 and were less willing to walk at Tex30. Conclusions and relevance Cats receiving alfaxalone had a longer but better quality recovery. Cardiorespiratory parameters were stable and within clinically acceptable values following IM injection of either alfaxalone or ketamine in healthy cats. Intramuscular alfaxalone is a suitable alternative to ketamine for short procedures requiring anaesthesia when used in combination with dexmedetomidine and butorphanol. PMID- 27401922 TI - Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway. AB - The objective of our study was to assess the radioprotective effect of flavonoids extracted from Rosa roxburghii Tratt (FRT) and investigate the role of Bcl 2(Ca(2+))/Caspase-3/PARP-1 pathway in radiation-induced apoptosis. Cells and mice were exposed to (60)Co gamma-rays at a dose of 6 Gy. The radiation treatment induced significant effects on tissue pathological changes, apoptosis, Ca(2+), ROS, DNA damage, and expression levels of Bcl-2, Caspase-3 (C-Caspase-3), and PARP-1. The results showed that FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, promoted the formation of spleen nodules, resisted sperm aberration, and protected the thymus. FRT significantly reduced cell apoptosis compared with the irradiation group. The expression of Ca(2+) and C-Caspase-3 was decreased after FRT treatment compared with the radiation-treated group. At the same time, expression of prototype PARP-1 and Bcl-2 increased, leading to a decrease in the percentage of apoptosis cells in FRT treatment groups. We conclude that FRT acts as a radioprotector. Apoptosis signals were activated via the Bcl-2(Ca(2+))/Caspase 3/PARP-1 pathway in irradiated cells and FRT inhibited this pathway of apoptosis by down-regulation of C-Caspase-3 and Ca(2+) and up-regulation of prototype PARP 1 and Bcl-2. PMID- 27401924 TI - Engineering the growth pattern and cell morphology for enhanced PHB production by Escherichia coli. AB - E. coli JM109?envC?nlpD deleted with genes envC and nlpD responsible for degrading peptidoglycan (PG) led to long filamentous cell shapes. When cell fission ring location genes minC and minD of Escherichia coli were deleted, E. coli JM109?minCD changed the cell growth pattern from binary division to multiple fissions. Bacterial morphology can be further engineered by overexpressing sulA gene resulting in inhibition on FtsZ, thus generating very long cellular filaments. By overexpressing sulA in E. coli JM109?envC?nlpD and E. coli JM109?minCD harboring poly(3-hydroxybutyrate) (PHB) synthesis operon phbCAB encoded in plasmid pBHR68, respectively, both engineered cells became long filaments and accumulated more PHB compared with the wild-type. Under same shake flask growth conditions, E. coli JM109?minCD (pBHR68) overexpressing sulA grown in multiple fission pattern accumulated approximately 70 % PHB in 9 g/L cell dry mass (CDM), which was significantly higher than E. coli JM109?envC?nlpD and the wild type, that produced 7.6 g/L and 8 g/L CDM containing 64 % and 51 % PHB, respectively. Results demonstrated that a combination of the new division pattern with elongated shape of E. coli improved PHB production. This provided a new vision on the enhanced production of inclusion bodies. PMID- 27401923 TI - Characterization of mutants of a tyrosine ammonia-lyase from Rhodotorula glutinis. AB - In the phenylpropanoid production process, p-coumaric acid is the most important intermediate metabolite. It is generally accepted that the activity of tyrosine ammonia-lyase (TAL), which converts L-tyrosine to p-coumaric acid, represents the rate-limiting step. Therefore, an error-prone PCR-based random mutagenesis strategy was utilized for screening variants with higher catalytic activity. After rounds of screening, three variant enzymes were obtained, exhibiting improved production rates of 41.2, 37.1, and 38.0 %, respectively. Variants associated with increased expression level (S9N), improved catalytic efficiency (A11T), and enhanced affinity between TAL and L-tyrosine (E518V) were identified as beneficial amino acid substitutions by site-directed mutagenesis. Combining all of the beneficial amino acid substitutions, a variant, MT-S9N/-A11T/-E518V, exhibiting the highest catalytic activity was obtained. The K m value of MT-S9N/ A11T/-E518V decreased by 25.4 % compare to that of wild-type, while the activity, k cat/K m, and p-coumaric-acid yield were improved by 36.5, 31.2, and 65.9 %, respectively. Furthermore, the secondary structure of the 5'-end of MT-S9N mRNA and the three-dimensional protein structure of MT-E518V were modeled. Therefore, two potential mechanisms were speculated: (1) a simplified mRNA 5'-end secondary structure promotes TAL expression and (2) anchoring the flexible loop region (Glu325-Arg336) to maintain the active-site pocket opening ensures easy access by the L-tyrosine to the active site and thus improves p-coumaric acid yields. PMID- 27401925 TI - Biosensoric potential of microbial fuel cells. AB - Recent progress in microbial fuel cell (MFC) technology has highlighted the potential of these devices to be used as biosensors. The advantages of MFC-based biosensors are that they are phenotypic and can function in either assay- or flow through formats. These features make them appropriate for contiguous on-line monitoring in laboratories and for in-field applications. The selectivity of an MFC biosensor depends on the applied microorganisms in the anodic compartment where electron transfer (ET) between the artificial surface (anode) and bacterium occurs. This process strongly determines the internal resistance of the sensoric system and thus influences signal outcome and response time. Despite their beneficial characteristics, the number of MFC-based biosensoric applications has been limited until now. The aim of this mini-review is to turn attention to the biosensoric potential of MFCs by summarizing ET mechanisms on which recently established and future sensoric devices are based. PMID- 27401926 TI - Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model. AB - Mixed chimerism is a promising approach to inducing allograft and xenograft tolerance. Mixed allogeneic and xenogeneic chimerism in mouse models induced specific tolerance and global hyporesponsiveness, respectively, of host mouse natural killer (NK) cells. In this study, we investigated whether pig/human mixed chimerism could tolerize human NK cells in a humanized mouse model. Our results showed no impact of induced human NK cell reconstitution on porcine chimerism. NK cells from most pig/human mixed chimeric mice showed either specifically decreased cytotoxicity to pig cells or global hyporesponsiveness in an in vitro cytotoxicity assay. Mixed xenogeneic chimerism did not hamper the maturation of human NK cells but was associated with an alteration in NK cell subset distribution and interferon gamma (IFN-gamma) production in the bone marrow. In summary, we demonstrate that mixed xenogeneic chimerism induces human NK cell hyporesponsiveness to pig cells. Our results support the use of this approach to inducing xenogeneic tolerance in the clinical setting. However, additional approaches are required to improve the efficacy of tolerance induction while ensuring adequate NK cell functions. PMID- 27401927 TI - Low T3 levels as a predictor marker predict the prognosis of patients with acute ischemic stroke. AB - BACKGROUND: Early and accurate prediction of outcome in acute stroke is important. The aim of this prospective study was to explore the correlation between serum triiodothyronine level and prognosis in acute ischemic stroke patients. METHODS: A prospective observational study which included 359 consecutive patients with acute ischemic stroke from December 2014 to November 2015 was interrogated. Serum triiodothyronine (T3) concentrations were measured on admission to understand their value in predicting functional outcome within 90 d using multivariable models adjusted for confounding factors. Receiver operating characteristic (ROC) curves were calculated to define the best cut-off value of triiodothyronine to predict outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC). RESULTS: Triiodothyronine was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome within 90 d (p = 0.01). Binary logistic regression analyses revealed that lower triiodothyronine concentrations on admission were associated with a risk for poor outcomes (OR 0.05, 95% CI 0.01-0.25; p < 0.01). In addition, in ROC curve analysis, triiodothyronine may improve the National Institutes of Health Stroke Scale (NIHSS) score in predicting functional outcome. The combined model AUROC was 0.84 for 30 d and 0.91 for 90 d, which were both significantly higher than the AUROCs of original NIHSS (0.83 and 0.87), triiodothyronine (0.64 and 0.69) and age (0.57 and 0.68) (all p < 0.05). CONCLUSIONS: Low serum triiodothyronine levels can be a predictive marker of short-term outcome after ischemic stroke. A combined model (triiodothyronine, age and NIHSS score) can add significant additional predictive information to the clinical score of the NIHSS. PMID- 27401928 TI - Myosin-I molecular motors at a glance. AB - Myosin-I molecular motors are proposed to play various cellular roles related to membrane dynamics and trafficking. In this Cell Science at a Glance article and the accompanying poster, we review and illustrate the proposed cellular functions of metazoan myosin-I molecular motors by examining the structural, biochemical, mechanical and cell biological evidence for their proposed molecular roles. We highlight evidence for the roles of myosin-I isoforms in regulating membrane tension and actin architecture, powering plasma membrane and organelle deformation, participating in membrane trafficking, and functioning as a tension sensitive dock or tether. Collectively, myosin-I motors have been implicated in increasingly complex cellular phenomena, yet how a single isoform accomplishes multiple types of molecular functions is still an active area of investigation. To fully understand the underlying physiology, it is now essential to piece together different approaches of biological investigation. This article will appeal to investigators who study immunology, metabolic diseases, endosomal trafficking, cell motility, cancer and kidney disease, and to those who are interested in how cellular membranes are coupled to the underlying actin cytoskeleton in a variety of different applications. PMID- 27401930 TI - Smile and laughter elicited by electrical stimulation of the frontal operculum. AB - Laughter and smile are typical expressions of mirth and fundamental means of social communication. Despite their general interest, the current knowledge about the brain regions involved in the production of these expressions is still very limited, and the principal insights come from electrical stimulation (ES) studies in patients, in which, nevertheless, laughter or smile have been elicited very rarely. Previous studies showed that laughter is evoked by the stimulation of nodes of an emotional network encompassing the anterior cingulate, the superior frontal and basal temporal cortex. A common feature of these stimulation studies is that the facial expression was always accompanied by motor awareness and often by mirth, in line with the affective functions attributed to these regions. Little is known, in contrast, on the neural basis of the voluntary motor control of this expression. The objective of this study was to investigate the effect of ES of the frontal operculum (FO), which is considered a crucial node for the linkage of the voluntary motor system for emotional expression and limbic emotional network. We report the case of ES applied to the frontal operculum (FO) in four patients with drug-resistant focal epilepsy undergoing stereo electroencephalographic (SEEG) implantation of intracerebral electrodes. In all patients, ES applied to the FO produced laughter or smile. Interestingly, in one patient, the production of a smiling expression was also clearly accompanied by the lack of motor awareness. Since the lack of motor awareness has been previously observed only after the stimulation of the voluntary motor network, we speculate that FO is involved in the voluntary control of facial expressions, and is placed at the interface with the emotional network, gating limbic information to the motor system. PMID- 27401929 TI - Addition of arabinoxylan and mixed linkage glucans in porcine diets affects the large intestinal bacterial populations. AB - PURPOSE: To investigate the effects of two cereal soluble dietary fibres (SDF), wheat arabinoxylan (AX) and oat-mixed linkage glucans (MLG), on fermentative end products and bacterial community profiles of the porcine caecum (Cae) and distal colon (DC). We hypothesised that feeding pigs these SDF would stimulate Cae and DC carbohydrate fermentation, resulting in a modification of the resident bacterial communities. METHODS: Five groups of six pigs were each fed one diet based on wheat starch (WS) only, or treatment diets in which some WS was replaced by 10 % AX, or 10 % MLG, a combination of 5 % AX:5 % MLG (AXMLG), or completely replaced with ground whole wheat. Post-euthanasia, Cae and DC digesta were collected for analysis of fermentative end-products, and bacterial community profiles were determined by 16S rRNA gene amplicon 454 pyrosequencing. RESULTS: Across all the SDF-containing diets, predominantly in the proximal region of the large intestine, Prevotella, Lactobacillus, Mitsuokella and Streptococcus were most significantly influenced (P < 0.05), while notable changes were observed for the Ruminococcaceae and Lachnospiraceae families in the Cae and DC. The addition of MLG or AXMLG had the greatest effect of influencing bacterial profiles, reducing sequence proportions assigned to the genus Clostridium, considered detrimental to gut health, with associated increases in short-chain fatty acid and reduced ammonia concentrations. CONCLUSIONS: This study demonstrated how the cereal SDF AX and MLG altered the large intestinal bacterial community composition, particularly proximally, further giving insights into how diets rich in specific complex carbohydrates shift the bacterial population, by increasing abundance and promoting greater diversity of those bacteria considered beneficial to gut health. PMID- 27401931 TI - Risk factors for local complications in children with community-acquired pneumonia. AB - AIM: The aim of this study was to evaluate the factors that could predict the development of local complications (parapneumonic effusion/pleural empyema, necrotizing pneumonia, and lung abscess) in children with community-acquired pneumonia (CAP). METHODS: Demographic, clinical, and laboratory data were prospectively collected and compared in children with noncomplicated and complicated CAP. RESULTS: Two-hundred and three patients aged from 2 months to 17 years were enrolled. There were 141 and 62 children with noncomplicated and complicated CAP, respectively. Significantly longer duration of fever and a higher level of acute phase reactants were demonstrated in complicated when noncomplicated to complicated CAP. Asymmetric chest pain as well as prehospital treatment with ibuprofen and acetaminophen were significantly more common in patients with complicated CAP (P < .001, P = .02 and P = .003, respectively). Preadmission cumulative dose of ibuprofen exceeding 78.3 mg/kg (median dose for the entire group) was associated with 2.5-fold higher odds ratio (OR) for CAP complications [OR 2.54 CI (1.31-4.94); P = .008)]. In contrast, pneumococcal vaccination was associated with lower odds ratio [OR.03 CI (.23-.89); P = .03] for local complications. CONCLUSIONS: Some clinical and laboratory data including chest pain, longer duration of fever, higher acute phase reactants, and especially preadmission treatment with ibuprofen or acetaminophen were associated with local complications of CAP. The results of this study highlight the association between the dose of ibuprofen and local CAP complications. PMID- 27401932 TI - Early health economic modelling of single-stage cartilage repair. Guiding implementation of technologies in regenerative medicine. AB - Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair - such as autologous chondrocyte implantation (ACI) - plus increasing healthcare costs, and market competition, are forcing a shift in focus from two-stage to single-stage interventions that are more cost-effective. Early health economic models are expected to provide essential insight in the parameters driving the cost-effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost-effectiveness ratio (ICER) of a new investigator-driven single stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost-effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of ?30 000/QALY. One way sensitivity analysis was performed to identify those parameters that drive the cost-effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be ?11 797, ?29 741 and ?6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from ?147 513/QALY to ?28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost-effective treatment option for smaller defects, a single-stage tissue engineering procedure can replace ACI to improve the cost-effectiveness for treating larger defects, especially if clinical non-inferiority can be achieved. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401933 TI - Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time. AB - The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27401934 TI - Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy. AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other. PMID- 27401935 TI - Wavelength dependence of photon-induced photoacoustic streaming technique for root canal irrigation. AB - Laser-enhanced irrigation of complex root canals appears to be a very promising technique to improve the outcome of root canal treatment. This applies, in particular, if the technique can be effective at very low laser energies in irrigating not only the main canal but also the small lateral canals. This is important in order to avoid potential undesirable effects at higher laser energies such as temperature increase, dentin ablation, or extrusion of irrigating solution beyond the apical foramen. An improved understanding of the role of laser parameters, such as laser wavelength and pulse duration, in irrigation of lateral canals is therefore desired in order to optimize treatment efficacy. The influence of laser wavelength and pulse duration on cavitation phenomena was studied using shadow photography and a method of measuring fluid flow in lateral canals based on tracking of movements of small air bubbles naturally forming in liquid as a result of laser agitation. A simulated model of a root canal including a narrow lateral canal designed to represent typical root canal morphology was used for the water flow measurements. The following three laser wavelengths with relatively high absorption in water were studied: Er:YAG (2.94 MUm), Er,Cr:YSGG (2.73 MUm), and Nd:YAP (1.34 MUm). Among the three wavelengths studied, the Er:YAG laser wavelength was found to be the most effective in formation of cavitation bubbles and in generating fluid motions within narrow lateral canals. A comparison between the shadow photography and fluid motion data indicates that it is the bubble's radius and not the bubble's volume that predominantly influences the fluid motion within lateral canals. Based on the results of our study, it appears that effective minimally invasive laser-assisted irrigation can be performed with low Er:YAG laser pulse energies below 10 mJ. PMID- 27401936 TI - Segmentation of the foveal microvasculature using deep learning networks. AB - Accurate segmentation of the retinal microvasculature is a critical step in the quantitative analysis of the retinal circulation, which can be an important marker in evaluating the severity of retinal diseases. As manual segmentation remains the gold standard for segmentation of optical coherence tomography angiography (OCT-A) images, we present a method for automating the segmentation of OCT-A images using deep neural networks (DNNs). Eighty OCT-A images of the foveal region in 12 eyes from 6 healthy volunteers were acquired using a prototype OCT-A system and subsequently manually segmented. The automated segmentation of the blood vessels in the OCT-A images was then performed by classifying each pixel into vessel or nonvessel class using deep convolutional neural networks. When the automated results were compared against the manual segmentation results, a maximum mean accuracy of 0.83 was obtained. When the automated results were compared with inter and intrarater accuracies, the automated results were shown to be comparable to the human raters suggesting that segmentation using DNNs is comparable to a second manual rater. As manually segmenting the retinal microvasculature is a tedious task, having a reliable automated output such as automated segmentation by DNNs, is an important step in creating an automated output. PMID- 27401937 TI - Depth enhancement in spectral domain optical coherence tomography using bidirectional imaging modality with a single spectrometer. AB - A method for depth enhancement is presented using a bidirectional imaging modality for spectral domain optical coherence tomography (SD-OCT). Two precisely aligned sample arms along with two reference arms were utilized in the optical configuration to scan the samples. Using exemplary images of the optical resolution target, Scotch tape, a silicon sheet with two needles, and a leaf, we demonstrated how the developed bidirectional SD-OCT imaging method increases the ability to characterize depth-enhanced images. The results of the developed system were validated by comparing the images with the standard OCT configuration (single-sample arm setup). Given the advantages of higher resolution and the ability to visualize deep morphological structures, this method can be utilized to increase the depth dependent fall-off in samples with limited thickness. Thus, the proposed bidirectional imaging modality is apt for cross-sectional imaging of entire samples, which has the potential capability to improve the diagnostic ability. PMID- 27401938 TI - Off-label drug use and temporary recommendations for use: Rearranging the deckchairs on the Titanic? PMID- 27401939 TI - Facial nerve paralysis as initial symptom of langerhans cell histiocytosis. PMID- 27401940 TI - Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. METHODS: To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. RESULTS: Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. CONCLUSION: Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to an improvement of neuromuscular disease treatment in Japan. PMID- 27401942 TI - Improved Mood State and Absence of Sex Differences in Response to the Stress of Army Basic Combat Training. AB - BACKGROUND: It is reported that women are more susceptible to stress than men but they have not been compared in stressful, real-world, team-centered, occupational/training environments. This study investigated effects of Army Basic Combat Training (BCT), a structured military training program, on the mood of young adult men and women. METHODS: Using the Profile of Mood States (POMS) questionnaire, 169 soldiers (98 men and 71 women) were assessed prior to starting BCT and after each phase of training. RESULTS: Significant improvements were found in five of six subscales over the course of BCT. Men and women responded positively and similarly to BCT. POMS scores attributable to an interaction of time and each factor of sex, age group, education level, ethnicity, and race were not significantly different. CONCLUSIONS: When studied in the same environment and exposed to the same stressors, men and women in this study responded similarly. The positive changes in mood in both sexes during BCT appear to result from the interaction of a structured physical and cognitive training program conducted in a team-oriented environment, and indicate that BCT enhances soldier mood similarly regardless of sex. PMID- 27401943 TI - Tele-aesthetics in South Asia. AB - BACKGROUND: Telemedicine is becoming increasingly popular. The best use for it is in the field of aesthetic dermatology - where conditions are not life threatening, and treatments can be topical and very safe. AIMS: In this study, we demonstrate that a simple store-and-forward telemedicine system can be applied safely to the field of aesthetic dermatology. METHODS AND MATERIALS: This was a prospective study was carried out in Singapore. A total of 102 patients filled up a medical questionnaire and submitted photographs via our online system. Upon submission, there was an independent doctor on the back-end who would review their medical details and their photographs and make diagnoses and recommendations based on this information. There was another doctor who examined the patients face-to-face. Diagnoses made by the online doctor and by the face-to face doctor were compared for congruency. RESULTS: A total of 358 diagnoses were made by the face-to-face doctor from 102 patients; 346 diagnoses were made by the teleconsultation doctor. For the purpose of this study, the diagnoses made by the FTFD were presumed to be correct. There was total agreement between both doctors in 342 diagnoses, giving a concordance rate of 95.5%. There were 12 missed diagnoses by the teleconsultation doctor and four discordant diagnoses. DISCUSSION: Our system demonstrates that a store-and-forward system enables our doctor to make accurate skin diagnoses. Our system was also able to detect dangerous conditions such as melanomas, skin cancers, actinic keratosis, and other dangerous diagnoses. There were discordant or missed diagnoses. This was mostly attributed to poor photograph quality. CONCLUSION: Emerging telemedicine technologies should be rigorously evaluated before they become widely implemented. Any system of value must uphold certain principles. It has to be fundamentally sound, safe, and clearly beneficial to the patient. With current technological limitations, the best use of such a system would be in aesthetics. PMID- 27401944 TI - Switchable polarization in an unzipped graphene oxide monolayer. AB - Ferroelectricity in low-dimensional oxide materials is generally suppressed at the scale of a few nanometers, and has attracted considerable attention from both fundamental and technological aspects. Graphene is one of the thinnest materials (one atom thick). Therefore, engineering switchable polarization in non-polar pristine graphene could potentially lead to two-dimensional (2D) ferroelectric materials. In the present study, based on density functional theory, we show that an unzipped graphene oxide (UGO) monolayer can exhibit switchable polarization due to its foldable bonds between the oxygen atom and two carbon atoms underneath the oxygen. We find that a free standing UGO monolayer exhibits antiferroelectric switchable polarization. A UGO monolayer can be obtained as an intermediate product during the chemical exfoliation process of graphene. Interestingly, despite its dimensionality, our estimated polarization in a UGO monolayer is comparable to that in bulk ferroelectric materials (e.g., ferroelectric polymers). Our calculations could help realize antiferroelectric switchable polarization in 2D materials, which could find various potential applications in nanoscale devices such as sensors, actuators, and capacitors with high energy storage density. PMID- 27401941 TI - Nanoparticles for imaging and treatment of metastatic breast cancer. AB - INTRODUCTION: Metastatic breast cancer is one of the most devastating cancers that have no cure. Many therapeutic and diagnostic strategies have been extensively studied in the past decade. Among these strategies, cancer nanotechnology has emerged as a promising strategy in preclinical studies by enabling early identification of primary tumors and metastases, and by effective killing of cancer cells. Areas covered: This review covers the recent progress made in targeting and imaging of metastatic breast cancer with nanoparticles, and treatment using nanoparticle-enabled chemo-, gene, photothermal- and radio therapies. This review also discusses recent developments of nanoparticle-enabled stem cell therapy and immunotherapy. Expert opinion: Nanotechnology is expected to play important roles in modern therapy for cancers, including metastatic breast cancer. Nanoparticles are able to target and visualize metastasis in various organs, and deliver therapeutic agents. Through targeting cancer stem cells, nanoparticles are able to treat resistant tumors with minimal toxicity to healthy tissues/organs. Nanoparticles are also able to activate immune cells to eliminate tumors. Owing to their multifunctional, controllable and trackable features, nanotechnology-based imaging and therapy could be a highly potent approach for future cancer research and treatment. PMID- 27401945 TI - Incidental focal epidermolytic hyperkeratosis in rosacea. PMID- 27401947 TI - The clinical symptoms of Parkinson's disease. AB - In this review, the clinical features of Parkinson's disease, both motor and non motor, are described in the context of the progression of the disease. Also briefly discussed are the major treatment strategies and their complications. Parkinson's disease is a slowly progressing neurodegenerative disorder, causing impaired motor function with slow movements, tremor and gait and balance disturbances. A variety of non-motor symptoms are common in Parkinson's disease. They include disturbed autonomic function with orthostatic hypotension, constipation and urinary disturbances, a variety of sleep disorders and a spectrum of neuropsychiatric symptoms. This article describes the different clinical symptoms that may occur and the clinical course of the disease. This article is part of a special issue on Parkinson disease. PMID- 27401946 TI - Capsaicin attenuates spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities. AB - This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal hyperthermia. Capsaicin (0.33 mg kg-1 ) was administered subcutaneously to mice one hour before heat stress (HS) in a 43 degrees C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL-positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70-kDa protein 1 (Hsp72) and BCL2 associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B-cell lymphoma-extra large (Bcl-xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre-treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL-positive cells, and Bcl-xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities. PMID- 27401948 TI - Measurement of Dabigatran Drug Levels to Manage Patients Taking Interacting Drugs: A Case Report. PMID- 27401950 TI - Abdominal Tuberculosis Presenting as a Malignant Masquerader. PMID- 27401949 TI - Association of 30-Day All-Cause Readmission with Long-Term Outcomes in Hospitalized Older Medicare Beneficiaries with Heart Failure. AB - BACKGROUND: Heart failure is the leading cause for 30-day all-cause readmission. We examined the impact of 30-day all-cause readmission on long-term outcomes and cost in a propensity score-matched study of hospitalized patients with heart failure. METHODS: Of the 7578 Medicare beneficiaries discharged with a primary diagnosis of heart failure from 106 Alabama hospitals (1998-2001) and alive at 30 days after discharge, 1519 had a 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without a 30-day all-cause readmission, balanced on 34 baseline characteristics (mean age 75 years, 56% women, 24% African American). RESULTS: During 2-12 months of follow-up after discharge from index hospitalization, all-cause mortality occurred in 41% and 27% of matched patients with and without a 30-day all-cause readmission, respectively (hazard ratio 1.68; 95% confidence interval 1.48-1.90; P <.001). This harmful association of 30-day all-cause readmission with mortality persisted during an average follow-up of 3.1 (maximum, 8.7) years (hazard ratio 1.33; 95% confidence interval 1.22-1.45; P <.001). Patients with a 30-day all-cause readmission had higher cumulative all cause readmission (mean, 6.9 vs 5.1; P <.001), a longer cumulative length of stay (mean, 51 vs 43 days; P <.001), and a higher cumulative cost (mean, $38,972 vs $34,025; P = .001) during 8.7 years of follow-up. CONCLUSIONS: Among Medicare beneficiaries hospitalized for heart failure, 30-day all-cause readmission was associated with a higher risk of subsequent all-cause mortality, higher number of cumulative all-cause readmission, longer cumulative length of stay, and higher cumulative cost. PMID- 27401951 TI - Double Jeopardy: Autoimmune Myelofibrosis with Pyoderma Gangrenosum. PMID- 27401952 TI - Hepatocellular Carcinoma Masquerading as Worsening Dementia. PMID- 27401953 TI - Differentiating Radiculopathy from Lower Extremity Arthropathy. AB - Low back and lower extremity pain are among the most common complaints encountered by physicians. Distinguishing pain due to primary extremity pathology versus lumbar radiculopathy can be challenging. Careful physical examination and appropriate imaging with plain radiographs and advanced studies as needed are important in determining the cause of lower extremity complaints. Over utilization of advanced imaging may reveal otherwise asymptomatic spinal pathology and can lead to an incorrect diagnosis. In patients in whom surgical intervention is being considered by a spine or arthroplasty surgeon, intra articular or epidural steroid injections may help to reveal the underlying cause of pain via short-term symptomatic relief. Additionally, patients presenting with vague lower extremity pain after recent or distant joint arthroplasty should be considered for potential failure or infection of their implant before assuming the symptoms are coming from the lumbar spine. PMID- 27401955 TI - Is STAT3 and PTEN Expression Altered in Canine Prostate Cancer? AB - Signal transducer and activator of transcription 3 (STAT3) and phosphatase and tensin homologue (PTEN) are, respectively, an oncogene and tumour suppressor gene whose dysregulated expression in human prostate cancer is associated with increased malignancy and poor prognosis. Both markers were evaluated in 12 samples of canine benign prostatic hyperplasia (BPH) and 17 canine prostatic carcinomas (PCs) by immunohistochemistry, to understand their possible role in canine prostate carcinogenesis. STAT3 was expressed in 25% and 82.35% of BPH and PC, respectively, with a significantly higher number of STAT3-positive cells in malignant compared with hyperplastic lesions. Three PCs had occasional nuclear expression of STAT3. PTEN was expressed in BPH and PC with a similar distribution and percentage of positive cells; however, four PCs were PTEN negative. Solid PCs contained more STAT3-positive and fewer PTEN-positive cells compared with the other subtypes. A reduced number of PTEN-positive cells was observed in PCs with a high Gleason score (GS10), while no association was demonstrated between STAT3 expression and Gleason score. The data suggest that overexpression of STAT3 and downregulation of PTEN may be an important step in canine prostate carcinogenesis and both markers may be related to the histological subtypes of PC and the degree of differentiation of neoplastic cells. PMID- 27401954 TI - Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase delta. AB - Membrane fission is an essential cellular process by which continuous membranes split into separate parts. We have previously identified CtBP1-S/BARS (BARS) as a key component of a protein complex that is required for fission of several endomembranes, including basolateral post-Golgi transport carriers. Assembly of this complex occurs at the Golgi apparatus, where BARS binds to the phosphoinositide kinase PI4KIIIbeta through a 14-3-3gamma dimer, as well as to ARF and the PKD and PAK kinases. We now report that, when incorporated into this complex, BARS binds to and activates a trans-Golgi lysophosphatidic acid (LPA) acyltransferase type delta (LPAATdelta) that converts LPA into phosphatidic acid (PA); and that this reaction is essential for fission of the carriers. LPA and PA have unique biophysical properties, and their interconversion might facilitate the fission process either directly or indirectly (via recruitment of proteins that bind to PA, including BARS itself). PMID- 27401957 TI - Reply to a Letter to the Editor regarding "High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study". PMID- 27401956 TI - Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment. AB - Histotripsy is a non-invasive ultrasonic ablation method that uses cavitation to mechanically fractionate tissue into acellular debris. With a sufficient number of pulses, histotripsy can completely fractionate tissue into a liquid-appearing homogenate with no cellular structures. The location, shape and size of lesion formation closely match those of the cavitation cloud. Previous work has led to the hypothesis that the rapid expansion and collapse of histotripsy bubbles fractionate tissue by inducing large stress and strain on the tissue structures immediately adjacent to the bubbles. In the work described here, the histotripsy bulk tissue fractionation process is visualized at the cellular level for the first time using a custom-built 2-MHz transducer incorporated into a microscope stage. A layer of breast cancer cells were cultured within an optically transparent fibrin-based gel phantom to mimic cells inside a 3-D extracellular matrix. To test the hypothesis, the cellular response to single and multiple histotripsy pulses was investigated using high-speed optical imaging. Bubbles were always generated in the extracellular space, and significant cell displacement/deformation was observed for cells directly adjacent to the bubble during both bubble expansion and collapse. The largest displacements were observed during collapse for cells immediately adjacent to the bubble, with cells moving more than 150-300 MUm in less than 100 MUs. Cells often underwent multiple large deformations (>150% strain) over multiple pulses, resulting in the bisection of cells multiple times before complete removal. To provide theoretical support to the experimental observations, a numerical simulation was conducted using a single-bubble model, which indicated that histotripsy exerts the largest strains and cell displacements in the regions immediately adjacent to the bubble. The experimental and simulation results support our hypothesis, which helps to explain the formation of the sharp lesions formed in histotripsy therapy localized to the regions directly exposed to the bubbles. PMID- 27401958 TI - Plane-Wave Compounding in Automated Breast Volume Scanning: A Phantom-Based Study. AB - The goal of this study was to assess whether it is viable to implement plane-wave imaging in the Automated Breast Volume Scanner (ABVS) to speed up the acquisition process. This would allow breath-hold examinations, thus reducing breathing artifacts without loss of imaging quality. A calibration phantom was scanned in an Automated Breast Volume Scanner-mimicking setup using both dynamic receive focusing with a fixed transmit focus and unfocused plane-wave compounding. Contrast-to-noise ratio and lateral resolution were compared using two beamforming schemes, delay-and-sum and Stolt's f-k algorithm. Plane-wave compounding using only 11 compounding angles and Stolt's f-k algorithm provided image quality similar to that of focused transmission with dynamic receive focusing (contrast-to-noise ratios = 10.3 and 10.8 dB for Stolt's f-k migration with Hann apodization and focused transmission, respectively; full width at half maximum = 0.38 and 0.4 mm, respectively; all at 30-mm depth with transmit focus at 30 mm) with a higher signal-to-noise ratio at all depths. Furthermore, a full 3-D volume of a breast-mimicking phantom was scanned using this optimal set of compounding angles and different speeds (10, 20 and 50 mm/s) to assess the impact of scanning time on image quality. Only minor differences in contrast-to-noise ratio were found (cyst 1: 6.0 +/- 0.3 dB, cyst 2: 5.5 +/- 0.2 dB, cyst 3: 5.7 +/- 0.5 dB). These differences could not be correlated to the movement speeds, indicating that acquisition speed does not significantly affect image quality. Our results suggest that plane-wave imaging will enable breath-hold automated breast volume scanning examinations, eliminating breathing artifacts while otherwise preserving similar image quality. PMID- 27401959 TI - Systematic review with meta-analysis: ondansetron for vomiting in children with acute gastroenteritis. AB - BACKGROUND: Vomiting in children with acute gastroenteritis is a common symptom, and it is considered to be the main cause of failure of oral rehydration therapy. AIM: To systematically update evidence on the effects of ondansetron (5-HT3 serotonin antagonist) for vomiting in children with acute gastroenteritis. METHODS: The Cochrane Library, MEDLINE and EMBASE databases were searched up to April 2016, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. RESULTS: Ten RCTs involving 1215 participants were included. Treatment with ondansetron compared with placebo increased the chance for vomiting cessation up to 1 h after drug administration, relative risk, RR, 1.49 (95% confidence interval 1.17-1.89), but there was no difference between the groups after 4, 24 and 48 h. Treatment with ondansetron compared with placebo reduced the risk of failure of oral rehydration therapy, RR 0.5 (0.37-0.69), increased the intake of oral rehydration solution in 1 h and 4 h, mean difference: 43 mL/1 h (15.5-70.5), and 91 mL/4 h (35-147), respectively, reduced the risk of hospitalisation, RR 0.53 (0.29-0.97), and reduced the need for intravenous rehydration, RR 0.45 (0.31-0.63); however, it had no effect on the need for return visits to the emergency department, RR 1.14 (0.72-1.8). Adverse effects were similar in both groups. CONCLUSIONS: Compared with placebo, ondansetron administration for vomiting in children with acute gastroenteritis can improve the efficacy of oral rehydration therapy. PMID- 27401960 TI - Examining habituation of the startle reflex with the reinforcement sensitivity theory of personality. AB - The habituation of the acoustic startle reflex (ASR) was examined concerning individual differences in sensitivity to punishment (PUN) and sensitivity to reward (REW), within the general framework of the reinforcement sensitivity theory (RST) of personality. Two hypotheses derived from the RST were evaluated: the separable subsystems hypothesis and the joint subsystems hypothesis. In addition, we examined the direction of the relationship of PUN and REW with the habituation of the ASR. A habituation segment of electromyography recordings of the orbicularis oculi was assessed with an unconditional latent curve model. In accordance with the RST hypotheses, the relationship of PUN and REW on the habituation process was assessed with two conditional latent curve models. There was higher support for the separable subsystems hypothesis. In addition, PUN and REW related with the habituation trajectory of the ASR in the expected directions. Higher levels of PUN and lower levels of REW related with a slower habituation of the ASR, whereas lower levels of PUN and higher levels of REW related with a faster habituation of the ASR. PMID- 27401961 TI - Sarcopenia and Hip Structure Analysis Variables in a Group of Elderly Men. PMID- 27401962 TI - Potential Clinical Impact of Abdominal Aortic Calcification on Bone Density Lateral Spine Images. AB - Abdominal aortic calcification (AAC) predicts incident atherosclerotic cardiovascular disease (ASCVD) events and can be accurately identified on densitometric lateral spine images obtained at the time of bone densitometry. Our objective was to estimate the proportion of patients referred for bone densitometry who have a high level of AAC and are not already known to have ASCVD or to be at high risk for ASCVD. AAC was scored on densitometric lateral spine images of 2168 individuals blinded to clinical diagnoses or risk factors using the 24-point Framingham scale. We ascertained preexisting ASCVD diagnoses and risk factors using electronic health record data. We used the risk calculator of the American Heart Association (AHA) and the American College of Cardiology (ACC) to estimate the 10-yr risk of hard ASCVD outcomes (myocardial infarction, death caused by coronary heart disease, or nonfatal or fatal stroke). A high level of AAC (AAC score >=5) was present in 41 (6.1%, 95% confidence interval [CI]: 4.4% 8.2%) of those aged less than 65 yr, in 253 (23.1%, 95% CI: 20.7%-25.7%) of those aged 65-74 yr, and in 153 (37.8%, 95% CI: 33.0%-42.7%) of those aged 75-80 yr. Among those aged 65-74 yr, 16.9% (95% CI: 14.7%-19.3%) had a high level of AAC and no prior clinical diagnosis of ASCVD, but only 2.4% had a high level of AAC and a predicted 10-yr risk of hard ASCVD outcomes <7.5%. AAC is common among those aged 65 yr and older who were referred for bone densitometry and had no known ASCVD, although these individuals can also be recognized as being at intermediate to high risk using the AHA-ACC ASCVD risk calculator. Further studies regarding the impact of identification of AAC on provider and patient cardiovascular disease risk management choices are warranted. PMID- 27401963 TI - MnTBAP increases BMPR-II expression in endothelial cells and attenuates vascular inflammation. AB - AIMS: The endothelium plays an important role during vascular inflammation. Previous data have demonstrated a high expression level of manganese-superoxide dismutase (MnSOD) in endothelial cells and suggested an important role of MnSOD in several cardiovascular diseases. Manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD and prevented the development of diabetes and obesity. However, its effect on vascular inflammation and the underlying mechanism is still unknown. METHODS AND RESULTS: Leukocyte adhesion was evaluated in-vivo and in-vitro using dynamic flow chamber and intravital microscopy in mice. Expression of adhesion molecules induced by TNFalpha and adhesion of leukocytes to the vessel wall were inhibited by MnTBAP. The anti-inflammatory effect of MnTBAP was partly mediated by up regulation of the BMPR-II and Smad dependent pathway. Additionally, MnTBAP decelerated the turn-over of endogenous BMPR-II. CONCLUSION: Our data demonstrate that MnTBAP activates Smad signaling, preserves the turn-over of BMPR-II and elicits anti-inflammatory effects in endothelial cells, partly mediated by BMPR II. This finding suggests a potential therapeutic impact of MnTBAP in the treatment of vascular inflammation. PMID- 27401965 TI - New BAR tools for mining expression data and exploring Cis-elements in Arabidopsis thaliana. AB - Identifying sets of genes that are specifically expressed in certain tissues or in response to an environmental stimulus is useful for designing reporter constructs, generating gene expression markers, or for understanding gene regulatory networks. We have developed an easy-to-use online tool for defining a desired expression profile (a modification of our Expression Angler program), which can then be used to identify genes exhibiting patterns of expression that match this profile as closely as possible. Further, we have developed another online tool, Cistome, for predicting or exploring cis-elements in the promoters of sets of co-expressed genes identified by such a method, or by other methods. We present two use cases for these tools, which are freely available on the Bio Analytic Resource at http://BAR.utoronto.ca. PMID- 27401964 TI - Sulforaphane induces neurovascular protection against a systemic inflammatory challenge via both Nrf2-dependent and independent pathways. AB - Sepsis is often characterized by an acute brain inflammation and dysfunction, which is associated with increased morbidity and mortality worldwide. Preventing cerebral leukocyte recruitment may provide the key to halt progression of systemic inflammation to the brain. Here we investigated the influence of the anti-inflammatory and anti-oxidant compound, sulforaphane (SFN) on lipopolysaccharide (LPS)-induced cellular interactions in the brain. The inflammatory response elicited by LPS was blunted by SFN administration (5 and 50mg/kg i.p.) 24h prior to LPS treatment in WT animals, as visualized and quantified using intravital microscopy. This protective effect of SFN was lost in Nrf2-KO mice at the lower dose tested, however 50mg/kg SFN revealed a partial effect, suggesting SFN works in part independently of Nrf2 activity. In vitro, SFN reduced neutrophil recruitment to human brain endothelial cells via a down regulation of E-selectin and vascular cell adhesion molecule 1 (VCAM-1). Our data confirm a fundamental dose-dependent role of SFN in limiting cerebral inflammation. Furthermore, our data demonstrate that not only is Nrf2 in part essential in mediating these neuroprotective effects, but they occur via down regulation of E-selectin and VCAM-1. In conclusion, SFN may provide a useful therapeutic drug to reduce cerebral inflammation in sepsis. PMID- 27401966 TI - A life-history perspective on the demographic drivers of structured population dynamics in changing environments. AB - Current understanding of life-history evolution and how demographic parameters contribute to population dynamics across species is largely based on assumptions of either constant environments or stationary environmental variation. Meanwhile, species are faced with non-stationary environmental conditions (changing mean, variance, or both) created by climate and landscape change. To close the gap between contemporary reality and demographic theory, we develop a set of transient life table response experiments (LTREs) for decomposing realised population growth rates into contributions from specific vital rates and components of population structure. Using transient LTREs in a theoretical framework, we reveal that established concepts in population biology will require revision because of reliance on approaches that do not address the influence of unstable population structure on population growth and mean fitness. Going forward, transient LTREs will enhance understanding of demography and improve the explanatory power of models used to understand ecological and evolutionary dynamics. PMID- 27401968 TI - Established and Emerging Biomarkers of Radiation Exposure. PMID- 27401967 TI - Improved Survival from Ovarian Cancer in Patients Treated in Phase III Trial Active Cancer Centres in the UK. AB - AIMS: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally. MATERIALS AND METHODS: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres. RESULTS: The analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre treated patients (95% confidence interval 9-73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres. CONCLUSION: The data suggest that international survival statistics are achieved in UK regional cancer centres. PMID- 27401969 TI - Recombinant human diamine oxidase activity is not inhibited by ethanol, acetaldehyde, disulfiram, diethyldithiocarbamate or cyanamide. AB - Human diamine oxidase (hDAO, EC 1.4.3.22) is the key enzyme in the degradation of extracellular histamine. Consumption of alcohol is a known trigger of mast cell degranulation in patients with mast cell activation syndrome. Ethanol may also interfere with enzymatic histamine degradation, but reports on the effects on DAO activity are controversial. There are also conflicting reports whether disulfiram, an FDA-approved agent in the treatment of alcohol dependence, inhibits DAO. We therefore investigated the inhibitory potential of ethanol and disulfiram and their metabolites on recombinant human DAO (rhDAO) in three different assay systems. Relevant concentrations of ethanol, acetaldehyde, and acetate did not inhibit rhDAO activity in an in vitro assay system using horseradish peroxidase (HRP) -mediated luminol oxidation. The aldehyde dehydrogenase (ALDH; EC 1.2.1.3) inhibitors cyanamide and its dimer dicyanamide also had no effect on DAO activity. In one assay system, the irreversible ALDH inhibitor disulfiram and its main metabolite diethyldithiocarbamate seemed to inhibit DAO activity. However, the decreased product formation was not due to a direct block of DAO activity but resulted from inhibition of peroxidase employed in the coupled system. Our in vitro data do not support a direct blocking effect of ethanol, disulfiram, and their metabolites on DAO activity in vivo. PMID- 27401970 TI - Specific detection of common pathogens of acute bacterial meningitis using an internally controlled tetraplex-PCR assay. AB - Accurate and timely diagnosis of acute bacterial meningitis is critical for antimicrobial treatment of patients. Although PCR-based methods have been widely used for the diagnosis of acute meningitis caused by bacterial pathogens, the main disadvantage of these methods is their high cost. This disadvantage has hampered the widespread use of molecular assays in many developing countries. The application of multiplex assays and "in-house" protocols are two main approaches that can reduce the overall cost of a molecular test. In the present study, an internally controlled tetraplex-PCR was developed and validated for the specific detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in cerebrospinal fluid (CSF) samples. The analysis of a panel of other human pathogens showed no cross-reactivity in the assay. The analytical sensitivity of the in-house assay was 792.3 copies/ml, when all three bacteria were presentin the specimens. This value was calculated as 444.5, 283.7, 127.8 copies/ml when only S. pneumoniae, N. meningitidis and H. influenzae, respectively, were present. To demonstrate the diagnostic performance of the assay, a total of 150 archival CSF samples were tested and compared with a commercial multiplex real-time PCR kit. A diagnostic sensitivity of 92.8% and a specificity of 95.1% were determined for the present tetraplex-PCR assay. The results indicate that the established method is sensitive, specific and cost effective, and can be used particularly in situations where the high cost of commercial kits prevents the use of molecular methods for the diagnosis of bacterial meningitis. PMID- 27401971 TI - Tracing residential mobility during the Merovingian period: An isotopic analysis of human remains from the Upper Rhine Valley, Germany. AB - OBJECTIVES: Written sources have provided information about the rise of Merovingian power and their territorial conquests after the disintegration of the Western Roman Empire, but the extent to which altered power relations in the newly annexed territories reshaped regional and local communities is poorly understood. The early medieval cemetery of Dirmstein, located in the Upper Rhine Valley, is one of the rare sites bearing archeological evidence of simultaneous use by an indigenous community and newcomers from outside the Merovingian core area, and it offers the opportunity to investigate residential mobility at the former Roman Rhine frontier during the Merovingian period. MATERIALS AND METHODS: We conducted strontium, oxygen, and carbon isotope analyses on human tooth enamel recovered from 25 sixth century inhumations at the Dirmstein cemetery to establish the presence of newcomers to the Upper Rhine region. RESULTS: The low delta(13) C values exhibited by the Dirmstein individuals revealed ingestion of a C3 terrestrial based diet, with no detectable contribution of C4 plants, which indicates the absence of individuals from regions where a C4 -based diet was common. Human (87) Sr/(86) Sr values well outside the local range of bioavailable strontium, in combination with low delta(18) O values, suggest a notable presence of newcomers from more eastern or high altitude regions. CONCLUSIONS: The isotopic evidence indicates that residential mobility was important and new settlers, most likely from outside the Merovingian core area, contributed to the settlement of the northern Upper Rhine Valley during the sixth century AD. PMID- 27401972 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27401973 TI - Novel acsF Gene Primers Revealed a Diverse Phototrophic Bacterial Population, Including Gemmatimonadetes, in Lake Taihu (China). AB - Anoxygenic phototrophs represent an environmentally important and phylogenetically diverse group of organisms. They harvest light using bacteriochlorophyll-containing reaction centers. Recently, a novel phototrophic bacterium, Gemmatimonas phototrophica, belonging to a rarely studied phylum, Gemmatimonadetes, was isolated from a freshwater lake in the Gobi Desert. To obtain more information about the environmental distribution of phototrophic Gemmatimonadetes, we collected microbial samples from the water column, upper sediment, and deeper anoxic sediment of Lake Taihu, China. MiSeq sequencing of the 16S rRNA, pufM, and bchY genes was carried out to assess the diversity of local phototrophic communities. In addition, we designed new degenerate primers of aerobic cyclase gene acsF, which serves as a convenient marker for both phototrophic Gemmatimonadetes and phototrophic Proteobacteria Our results showed that most of the phototrophic species in Lake Taihu belong to Alpha- and Betaproteobacteria Sequences of green sulfur and green nonsulfur bacteria (phototrophic Chlorobi and Chloroflexi, respectively) were found in the sediment. Using the newly designed primers, we identified a diverse community of phototrophic Gemmatimonadetes forming 30 operational taxonomic units. These species represented 10.5 and 17.3% of the acsF reads in the upper semiaerobic sediment and anoxic sediment, whereas their abundance in the water column was <1%. IMPORTANCE: Photosynthesis is one of the most fundamental biological processes on Earth. Recently, the presence of photosynthetic reaction centers has been reported from a rarely studied bacterial phylum, Gemmatimonadetes, but almost nothing is known about the diversity and environmental distribution of these organisms. The newly designed acsF primers were used to identify phototrophic Gemmatimonadetes from planktonic and sediment samples collected in Lake Taihu, China. The Gemmatimonadetes sequences were found mostly in the upper sediments, documenting the preference of Gemmatimonadetes for semiaerobic conditions. Our results also show that the phototrophic Gemmatimonadetes present in Lake Taihu were relatively diverse, encompassing 30 operational taxonomic units. PMID- 27401974 TI - North-Seeking Magnetotactic Gammaproteobacteria in the Southern Hemisphere. AB - Magnetotactic bacteria (MTB) comprise a phylogenetically diverse group of prokaryotes capable of orienting and navigating along magnetic field lines. Under oxic conditions, MTB in natural environments in the Northern Hemisphere generally display north-seeking (NS) polarity, swimming parallel to the Earth's magnetic field lines, while those in the Southern Hemisphere generally swim antiparallel to magnetic field lines (south-seeking [SS] polarity). Here, we report a population of an uncultured, monotrichously flagellated, and vibrioid MTB collected from a brackish lagoon in Brazil in the Southern Hemisphere that consistently exhibits NS polarity. Cells of this organism were mainly located below the oxic-anoxic interface (OAI), suggesting it is capable of some type of anaerobic metabolism. Magnetosome crystalline habit and composition were consistent with elongated prismatic magnetite (Fe3O4) particles. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that this organism belongs to a distinct clade of the Gammaproteobacteria class. The presence of NS MTB in the Southern Hemisphere and the previously reported finding of SS MTB in the Northern Hemisphere reinforce the idea that magnetotaxis is more complex than we currently understand and may be modulated by factors other than O2 concentration and redox gradients in sediments and water columns. IMPORTANCE: Magnetotaxis is a navigational mechanism used by magnetotactic bacteria to move along geomagnetic field lines and find an optimal position in chemically stratified sediments. For that, magnetotactic bacteria swim parallel to the geomagnetic field lines under oxic conditions in the Northern Hemisphere, whereas those in the Southern Hemisphere swim antiparallel to magnetic field lines. A population of uncultured vibrioid magnetotactic bacteria was discovered in a brackish lagoon in the Southern Hemisphere that consistently swim northward, i.e., the opposite of the overwhelming majority of other Southern Hemisphere magnetotactic bacteria. This finding supports the idea that magnetotaxis is more complex than previously thought. PMID- 27401975 TI - High Level of Spinosad Production in the Heterologous Host Saccharopolyspora erythraea. AB - Spinosad, a highly effective insecticide, has an excellent environmental and mammalian toxicological profile. Global market demand for spinosad is huge and growing. However, after much effort, there has been almost no improvement in the spinosad yield from the original producer, Saccharopolyspora spinosa Here, we report the heterologous expression of spinosad using Saccharopolyspora erythraea as a host. The native erythromycin polyketide synthase (PKS) genes in S. erythraea were replaced by the assembled spinosad gene cluster through iterative recombination. The production of spinosad could be detected in the recombinant strains containing the whole biosynthesis gene cluster. Both metabolic engineering and UV mutagenesis were applied to further improve the yield of spinosad. The final strain, AT-ES04PS-3007, which could produce spinosad with a titer of 830 mg/liter, has significant potential in industrial applications. IMPORTANCE: This work provides an innovative and promising way to improve the industrial production of spinosad. At the same time, it also describes a successful method of heterologous expression for target metabolites of interest by replacing large gene clusters. PMID- 27401976 TI - Basic Reproduction Number and Transmission Dynamics of Common Serogroups of Enterohemorrhagic Escherichia coli. AB - Understanding the transmission dynamics of pathogens is essential to determine the epidemiology, ecology, and ways of controlling enterohemorrhagic Escherichia coli (EHEC) in animals and their environments. Our objective was to estimate the epidemiological fitness of common EHEC strains in cattle populations. For that purpose, we developed a Markov chain model to characterize the dynamics of 7 serogroups of enterohemorrhagic Escherichia coli (O26, O45, O103, O111, O121, O145, and O157) in cattle production environments based on a set of cross sectional data on infection prevalence in 2 years in two U.S. states. The basic reproduction number (R0) was estimated using a Bayesian framework for each serogroup based on two criteria (using serogroup alone [the O-group data] and using O serogroup, Shiga toxin gene[s], and intimin [eae] gene together [the EHEC data]). In addition, correlations between external covariates (e.g., location, ambient temperature, dietary, and probiotic usage) and prevalence/R0 were quantified. R0 estimates varied substantially among different EHEC serogroups, with EHEC O157 having an R0 of >1 (~1.5) and all six other EHEC serogroups having an R0 of less than 1. Using the O-group data substantially increased R0 estimates for the O26, O45, and O103 serogroups (R0 > 1) but not for the others. Different covariates had distinct influences on different serogroups: the coefficients for each covariate were different among serogroups. Our modeling and analysis of this system can be readily expanded to other pathogen systems in order to estimate the pathogen and external factors that influence spread of infectious agents. IMPORTANCE: In this paper we describe a Bayesian modeling framework to estimate basic reproduction numbers of multiple serotypes of Shiga toxin-producing Escherichia coli according to a cross-sectional study. We then coupled a compartmental model to reconstruct the infection dynamics of these serotypes and quantify their risk in the population. We incorporated different sensitivity levels of detecting different serotypes and evaluated their potential influence on the estimation of basic reproduction numbers. PMID- 27401978 TI - Anthony Carl Kaeser. PMID- 27401977 TI - Long non-coding RNAs are major contributors to transcriptome changes in sunflower meiocytes with different recombination rates. AB - BACKGROUND: Meiosis is a form of specialized cell division that marks the transition from diploid meiocyte to haploid gamete, and provides an opportunity for genetic reassortment through recombination. Experimental data indicates that, relative to their wild ancestors, cultivated sunflower varieties show a higher recombination rate during meiosis. To better understand the molecular basis for this difference, we compared gene expression in male sunflower meiocytes in prophase I isolated from a domesticated line, a wild relative, and a F1 hybrid of the two. RESULTS: Of the genes that showed differential expression between the wild and domesticated genotypes, 63.62 % could not be identified as protein coding genes, and of these genes, 70.98 % passed stringent filters to be classified as long non-coding RNAs (lncRNAs). Compared to the sunflower somatic transcriptome, meiocytes express a higher proportion of lncRNAs, and the majority of genes with exclusive expression in meiocytes were lncRNAs. Around 40 % of the lncRNAs showed sequence similarity with small RNAs (sRNA), while 1.53 % were predicted to be sunflower natural antisense transcripts (NATs), and 9.18 % contained transposable elements (TE). We identified 6895 lncRNAs that are exclusively expressed in meiocytes, these lncRNAs appear to have higher conservation, a greater degree of differential expression, a higher proportion of sRNA similarity, and higher TE content relative to lncRNAs that are also expressed in the somatic transcriptome. CONCLUSIONS: lncRNAs play important roles in plant meiosis and may participate in chromatin modification processes, although other regulatory functions cannot be excluded. lncRNAs could also be related to the different recombination rates seen for domesticated and wild sunflowers. PMID- 27401979 TI - Stereoselective Metabolism of alpha-, beta-, and gamma-Hexabromocyclododecanes (HBCDs) by Human Liver Microsomes and CYP3A4. AB - This is the first study investigating the in vitro metabolism of alpha-, beta-, and gamma-hexabromocyclododecane (HBCD) stereoisomers in humans and providing semiquantitative metabolism data. Human liver microsomes were incubated with individual racemic mixtures and with individual stereoisomers of alpha-, beta-, and gamma-HBCDs, the hydroxylated metabolites formed were analyzed by liquid chromatography-tandem mass spectrometry, and the value of the intrinsic in vitro clearance (Clint,vitro) was calculated. Several mono- and dihydroxylated metabolites of alpha-, beta-, and gamma-HBCDs were formed, with mono-OH-HBCDs being the major metabolites. No stereoisomerization of any of the six alpha-, beta-, and gamma-HBCD isomers catalyzed by cytochrome P450 (CYP) enzymes occurred. The value of Clint,vitro of alpha-HBCDs was significantly lower than that of beta-HBCDs, which, in turn, was significantly lower than that of gamma HBCDs (p < 0.05). Such differences were explained by the significantly lower values of Clint,vitro of each alpha-HBCD stereoisomer than those of the beta- and gamma-HBCD stereoisomers. In addition, significantly lower values of Clint,vitro of the (-) over the (+)alpha- and beta-HBCD stereoisomers, but not gamma-HBCDs, were obtained. Our data offer a possible explanation of the enrichment of alpha HBCDs over beta- and gamma-HBCDs on the one hand and, on the other hand, of ( )alpha-HBCDs over (+)alpha-HBCDs previously reported in human samples. It also offers information about the mechanism resulting in such enrichments, the stereoisomer-selective metabolism of alpha-, beta-, and gamma-HBCDs catalyzed by CYPs with the lack of stereoisomerization. PMID- 27401980 TI - Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes. AB - BACKGROUND: Electronic cigarettes (e-cigarettes) are popular alternatives to conventional cigarettes among adult smokers wishing to reduce their exposure to harmful smoke constituents. However, little information exists on the relative internal exposures resulting from the exclusive or dual use of e-cigarettes. METHODS: Measurements of product use; adverse events; changes in smoking urge; and blood, urine and exhaled breath biomarkers of exposure (BoE) representing toxicants believed to contribute to smoking related diseases were made at baseline and after five days of product use in 105 clinically-confined smokers randomized into groups that partially or completely substituted their usual brand combustible cigarette with commercial e-cigarettes, or discontinued all nicotine and tobacco products. RESULTS: Subjects switching to e-cigarettes had significantly lower levels (29 %-95 %) of urinary BoEs after 5 days. Nicotine equivalents declined by 25 %-40 %. Dual users who substituted half of their self reported daily cigarette consumption with e-cigarettes experienced 7 %-38 % reductions, but had increases (1 %-20 %) in nicotine equivalents. Blood nicotine biomarker levels were lower in the cessation (75 %-96 %) and e-cigarette use groups (11 %-83 %); dual users had no significant reductions. All groups experienced significant decreases in exhaled CO (27 %-89 %). Exhaled NO increases (46 %-63 %) were observed in the cessation and e-cigarette use groups; dual users had minimal changes. By Day 5, all groups had greater reductions in smoking urge compared to cessation. However, reductions were larger in the dual use group. No serious adverse events were observed. CONCLUSIONS: Exposures to harmful smoke toxicants were observed to be lower in smokers who completely or partially replaced their cigarettes with e-cigarettes over five days. PMID- 27401981 TI - Continuous suturing with two anterior layers reduces post-operative complications and hospitalization time in pancreaticoenterostomy. AB - BACKGROUND: Most complications after pancreaticoduodenectomy (PD) were relation to pancreaticoenterostomy. We improved a new method of pancreaticoenterostomy that included the continuous suturing of the jejunum and the stump of the pancreas end-to-side with one layer posteriorly and two layers anteriorly. To evaluate the safety and efficiency of this new method, we introduced this retrospectively compared trial. METHODS: We compared 45 patients who had undergone pancreaticoduodenectomy with either the regular interrupted suturing method or the new continuous mattress suturing method in our hospital from September 2011 to March 2014. RESULTS: Although the total operation times were not reduced, the suturing time for the pancreaticoenterostomies in the continuous suture group (11.3 +/- 1.8 min) was greatly reduced compared with that for the interrupted suture group (14.1 +/- 2.9 min, p = 0.045). Importantly, the continuous mattress suturing method significantly decreased short-term post operative complications, including pancreatic leakage (p = 0.042). Furthermore, shorter hospitalization times were observed in the continuous mattress suture group (12.3 +/- 5.0 d) than in the interrupted suture group (24.2 +/- 11.6 d, p = 0.000). CONCLUSIONS: Continuous mattress suturing is a safe and effective pancreaticoenterostomy method that leads to reduced complications and hospitalization times. PMID- 27401982 TI - Treatment of Paecilomyces variotii pneumonia with posaconazole: case report and literature review. AB - The fungi Paecilomyces variotii is a potential pathogen in immunocompromised and immunocompetent patients. Their rare association with clinical disease results in scarce literature regarding susceptibility and treatment. Here, we discuss a case involving successful treatment of probable P. variotii pneumonia with posaconazole after treatment failure with voriconazole. The current literature related to antifungal susceptibility profiles, microbiological identification methods and clinical management of infections caused by this organism is also reviewed. PMID- 27401983 TI - Fatal air embolism as complication of percutaneous dilatational tracheostomy on venovenous extracorporeal membrane oxygenation, two case reports. AB - BACKGROUND: Tracheostomy is recommended in case of prolonged mechanical ventilation. Therefore, most patients with an indication for venovenous extracorporeal membrane oxygenation (ECMO) will also have an indication for tracheostomy. CASE PRESENTATION: We report 2 cases of fatal air embolism into the ECMO system as complication of percutaneous dilatational tracheostomy. Both patients had an AVALON ELITE(r) bi-caval cannula implanted draining blood from the vena cava superior and inferior. CONCLUSION: Since there is limited safety data on this specific group of patients, a routine early dilatational tracheostomy might be associated with a significant risk. PMID- 27401984 TI - Urethroplasty for treatment of long anterior urethral stricture: buccal mucosa graft versus penile skin graft-does the stricture length matter? AB - PURPOSE: To investigate the surgical outcomes of dorsal onlay urethroplasty (DOU) using buccal mucosa graft (BMG) or penile skin graft (PSG) and to assess the effect of stricture length in men with anterior urethral strictures. METHODS: A prospective cohort included men with anterior urethral strictures between 2008 and 2015. Patients underwent DOU using PSG or BMG. Patients had urethrography and uroflowmetry at 0, 3, 6, 12 months, and urethroscopy when needed. Student's t test, Mann-Whitney U tests, and Pearson's Chi-square test were used for analysis. RESULTS: Sixty-nine patients (43 +/- 14 year) were included, 31 received BMG, and 38 received PSG. Mean stricture length was 8 +/- 3 cm, mean operative time was 145 +/- 31 min, and mean follow-up was 56 +/- 10 mo. Success rate was 87 % (90 % BMG vs. 84 % PSG, p = 0.4). Mean operative time was significantly shorter in PSG group (136 +/- 29 min vs. 256 +/- 58 min, p = 0.0005). Complications of grade I developed in 36 % (wound infection = 10 %, postvoiding dribbling = 18.8 %). Thirty of 69 patients (43 %) had strictures >=8 cm, and 39 (57 %) had strictures <8 cm-success rate was equal for both subgroups (87 %). Mean blood loss, mean operative time, and incidence of postvoid dribbling were significantly lower in strictures <8 cm. CONCLUSION: BMG and PSG have comparable success rates in treatment of long anterior urethral strictures. Operative time is significantly longer in BMG. Long-segment strictures are associated with longer operative time, more blood loss, and more occurrence of postvoid dribbling. However, the length of the stricture has no influence on the success rate and functional outcomes of DOU. PMID- 27401985 TI - Evaluation of glomerular filtration rate by different equations in Chinese elderly with chronic kidney disease. AB - PURPOSE: Performance of equations in elderly with chronic kidney disease (CKD) was debated. We aimed to access the performances of estimating equations for glomerular filtration rate in Chinese elderly population with chronic kidney disease. METHODS: Participants [N = 218, median age, 82 (range 75-96)] with CKD underwent renal dynamic imaging using technetium-99m diethylene-triamine-penta acetic acid (99mTc-DTPA). The performances of glomerular filtration rate equations including the Cockcroft-Gault equation, the MDRD (Modification of Diet in Renal Disease) equation for Chinese, 3 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations, and 2 BIS (Berlin Initiative Study) equations were compared. RESULTS: Median mGFR was 47.62 (3.00-135.00) ml/min/1.73 m2. Smaller biases were shown in BIS-2 equation and CKD-EPI-Cr equation (0.63 ml/min/1.73 m2 and -1.22 ml/min/1.73 m2). Interquartile range of the differences was least with BIS-2 equation and CKD-EPI-Cr-Cys equation (4.36 ml/min/1.73 m2 and 9.17 ml/min/1.73 m2). For accuracy (percentage of eGFR within 30 % of the mGFR, P30), performance of BIS-2, CKD-EPI-Cr-Cys, and BIS-1 equation was superior (94.50, 89.91, and 88.53 %, respectively). In terms of accuracy (root-mean-square error, RMSE), BIS-2 equation, CKD-EPI-Cr-Cys equation, and BIS-1 equation also performed better (7.21 ml/min/1.73 m2, 8.87 ml/min/1.73 m2 and 9.82 ml/min/1.73 m2). GFR category misclassification rates were smaller in BIS-2 equation, CKD-EPI Cr-Cys equation and BIS-1 equation (16.51, 20.64, and 25.69 %, respectively). CONCLUSION: Compared with other equations, the BIS-2 equation performed better in the estimation of glomerular filtration rate for Chinese elderly with CKD aged 75 or above. PMID- 27401986 TI - Gastric mucosal irritation following oral exposure to sodium metabisulphite: A reproducible effect? AB - Sulphiting agents, such as sodium metabisulphite (SM), are used in food as bleaching agents and to prevent browning reactions. A 1972 repeat dose study in rats found that dietary sulphites caused irritation of the stomach with inflammation, hyperplasia and bleeding. We conducted a 7-day dietary study in rats to confirm that stomach lesions were the most sensitive toxicological endpoint. Rat feed was prepared daily with 0%, 0.25%, 0.5%, 1% or 4% (w/w) SM. Parameters included clinical signs, feed and water intake, bodyweight gain, haematology, serum protein chemistry, necropsy findings and gastrointestinal histopathology. There were no treatment-related clinical signs or gastrointestinal lesions. Mean bodyweight gain was markedly decreased in the 4% (w/w) SM group although feed consumption was marginally depressed. Slightly lower mean values for RBC, Hb, Hct, total WBC and lymphocyte count were observed in the 4% SM group with no evidence of compensatory haematopoiesis. The gastric lesions in rats observed in a 1972 study of dietary SM for 10-56 days could not be replicated. These findings create uncertainty around the most relevant toxicological endpoint to establish a suitable health based guidance value, which can only be overcome if a robust long-term dietary study is undertaken. PMID- 27401987 TI - [Pulmonary infections with non-tuberculous mycobacteria]. AB - In recent decades, an increasing incidence of pulmonary infections with non tuberculous mycobacteria has been reported, primarily affecting patients with structural lung diseases and/or immunosuppression. In Denmark, approximately 100 new cases of infection with non-tuberculous mycobacteria occur yearly, most commonly with Mycobac-terium avium complex. Diagnosis is based on clinical, radiological and microbiological criteria. Treatment is difficult, and outcomes are often poor. Antibiotic treatment should be performed by specialists with reference to international guidelines. PMID- 27401988 TI - [Skin biopsy and quantitative sensory testing can contribute to small fibre neuropathy diagnostics]. AB - Nerve conduction studies are normal in small fibre neuropathy and special methods such as skin biopsies or quantitative sensory testing are required for diagnosis. In skin biopsies, nerve fibres are stained immunohistochemically and loss of distal nerve endings can be quantified directly. Assessment of thermal detection thresholds is used to evaluate the function of the sensory thermal pathways, but cannot discriminate between central and peripheral lesions. Small fibre neuropathy is often associated with potentially treatable diseases, and treatment of neuropathic pain may be required. PMID- 27401989 TI - [Low molecular weight heparin as venous thromboembolism prophylaxis in hospitalized medical patients]. AB - In this study we reviewed the literature for meta-analyses investigating the effect and risk associated with low molecular weight heparin (LMWH) as venous thromboembolism (VTE) prophylaxis in hospitalized medical patients. Furthermore, we identified reputable clinical practice guidelines for VTE prophylaxis in hospitalized medical patients. We included six meta-analyses and two guidelines. Meta-analyses showed varying results of LMWH as VTE prophylaxis. Both guidelines recommend pharmacological VTE prophylaxis for selected hospitalized medical patients. PMID- 27401990 TI - [Retransplantation af fuldhud efter seponering af diatermiplade]. PMID- 27401991 TI - Osteogenic Capacity of Human Adipose-Derived Stem Cells is Preserved Following Triggering of Shape Memory Scaffolds. AB - Recent advances in shape memory polymers have enabled the study of programmable, shape-changing, cytocompatible tissue engineering scaffolds. For treatment of bone defects, scaffolds with shape memory functionality have been studied for their potential for minimally invasive delivery, conformal fitting to defect margins, and defect stabilization. However, the extent to which the osteogenic differentiation capacity of stem cells resident in shape memory scaffolds is preserved following programmed shape change has not yet been determined. As a result, the feasibility of shape memory polymer scaffolds being employed in stem cell-based treatment strategies remains unclear. To test the hypothesis that stem cell osteogenic differentiation can be preserved during and following triggering of programmed architectural changes in shape memory polymer scaffolds, human adipose-derived stem cells were seeded in shape memory polymer foam scaffolds or in shape memory polymer fibrous scaffolds programmed to expand or contract, respectively, when warmed to body temperature. Osteogenic differentiation in shape-changing and control scaffolds was compared using mineral deposition, protein production, and gene expression assays. For both shape-changing and control scaffolds, qualitatively and quantitatively comparable amounts of mineral deposition were observed; comparable levels of alkaline phosphatase activity were measured; and no significant differences in the expression of genetic markers of osteogenesis were detected. These findings support the feasibility of employing shape memory in scaffolds for stem cell-based therapies for bone repair. PMID- 27401992 TI - Brief Report: Parent-Teacher Discrepancies on the Developmental Social Disorders Scale (BASC-2) in the Assessment of High-Functioning Children with ASD. AB - This study compared parent and teacher ratings of ASD-related symptoms of 120 high-functioning children, ages 6-12 years with ASD (HFASD) using the Developmental Social Disorders (DSD) scale of the BASC-2. DSD ratings (parent and teacher) were significantly higher than normative estimates. The cross-informant comparison was significantly higher for parents (vs. teachers), and correlations (ICC and Pearson) between the informant groups were significant (but low in magnitude). Agreement among parents and teachers accurately placed 81 % of cases above the at-risk cutpoint for symptoms of ASD, and agreement was highest in the at-risk range of perceived symptoms. Additional analyses indicated a significant difference in the trend across the parent-teacher discrepancies, and no significant moderators of the discrepancies. Implications for assessment are provided. PMID- 27401993 TI - Aspects of Sexuality in Adolescents and Adults Diagnosed with Autism Spectrum Disorders in Childhood. AB - The literature concerning sexuality in autism spectrum disorders (ASDs) is limited regarding inappropriate sexual behaviours and paraphilias and its relation to age, verbal ability, symptom severity, intellectual ability, or adaptive functioning. A cohort of 184 adolescents and young adults (ages 15-39 years) with ASD diagnosed in childhood, including both low and high functioning individuals, was examined. The large majority were found to have a sexual interest and showed interest towards the opposite sex. Inappropriate sexual behaviours and paraphilias were reported for about a fourth of the individuals. No relationships were found between inappropriate sexual behaviours and any of the background variables listed above. However, associations were found between paraphilias and ASD symptom severity, intellectual ability, and adaptive functioning. PMID- 27401994 TI - Association of Autism Spectrum Disorder with Obsessive-Compulsive and Attention Deficit/Hyperactivity Traits and Response Inhibition in a Community Sample. AB - We examined co-occurrence of autism spectrum disorder (ASD) with (traits of) attention-deficit/hyperactivity (ADHD), obsessive-compulsive (OCD) and inhibition deficits in a community sample (n = 16,676) and tested whether having a sibling with ASD manifested in increased features of ADHD, OCD or inhibition deficits. Individuals with ASD had increased ADHD and OCD traits compared with individuals without ASD. Individuals with a sibling with ASD exhibited more ADHD traits than did individuals whose sibling did not have ASD. The "sibling effect" on manifestation of ADHD traits was observed in individuals with and without ASD. Having a sibling with ASD did not affect OCD traits. Inhibition was impaired in individuals with ASD who had a sibling with ASD only. PMID- 27401995 TI - Friendship networks and psychological well-being from late adolescence to young adulthood: a gender-specific structural equation modeling approach. AB - BACKGROUND: The importance of supportive social relationships for psychological well-being has been previously recognized, but the direction of associations between both dimensions and how they evolve when adolescents enter adulthood have scarcely been addressed. The present study aims to examine the gender-specific associations between self-reported friendship network quality and psychological well-being of young people during the transition from late adolescence to young adulthood by taking into account the direction of association. METHODS: A random sample of Swedes born in 1990 were surveyed at age 19 and again at age 23 regarding their own health and their relationships with a maximum of five self nominated friends. The response rate was 55.3 % at baseline and 43.7 % at follow up, resulting in 772 cases eligible for analysis. Gender-specific structural equation modeling was conducted to explore the associations between network quality and well-being. The measurement part included a latent measure of well being, whereas the structural part accounted for autocorrelation for network quality and for well-being over time and further examined the cross-lagged associations. RESULTS: The results show that network quality increased while well being decreased from age 19 to age 23. Females reported worse well-being at both time points, whereas no gender differences were found for network quality. Network quality at age 19 predicted network quality at age 23, and well-being at age 19 predicted well-being at age 23. The results further show positive correlations between network quality and well-being for males and females alike. The strength of the correlations diminished over time but remained significant at age 23. Simultaneously testing social causation and social selection in a series of competing models indicates that while there were no cross-lagged associations among males, there was a weak reverse association between well-being at age 19 and network quality at age 23 among females. CONCLUSIONS: The study contributes to the understanding of the direction of associations between friendship networks and psychological well-being from late adolescence to young adulthood by showing that while these dimensions are closely intertwined among males and females alike, females' social relationships seem to be more vulnerable to changes in health status. PMID- 27401996 TI - Vitamin D and oxidation-induced DNA damage: is there a connection? AB - Oxidation-induced damage to DNA can cause mutations, phenotypic changes and apoptosis. Agents that oppose such damage offer potential therapies for disease prevention. Vitamin D administration reportedly lowered DNA damage in type 2 diabetic mice, and higher DNA damage was reported in mononuclear cells of severely asthmatic patients who were vitamin D deficient. We hypothesised that lower vitamin D status associates with higher oxidation-induced DNA damage. Vitamin D deficiency (plasma 25(OH)D < 50 nmol/l) is highly prevalent worldwide, and association with DNA damage has high potential importance and impact in regard to the future health of vitamin D deficient young adults. In this study, oxidation-induced DNA damage in peripheral lymphocytes of 121 young (18-26 years) adults was measured using the formamidopyrimidine DNA glycosylase (FPG)-assisted comet assay. Plasma 25(OH)D was measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Correlational analysis was performed between 25(OH)D and DNA damage. Differences in DNA damage across tertiles of 25(OH)D were explored using analysis of variance. DNA damage in those with 25(OH)D <50 nmol and >=50 nmol/l was compared using the unpaired t-test. Mean (SD) DNA damage (as %DNA in comet tail) and plasma 25(OH)D were, respectively, 18.58 (3.39)% and 44.7 (13.03) nmol/l. Most (82/121; 68%) of the subjects were deficient in vitamin D (25(OH)D <50nmol/l). No significant correlation was seen between 25(OH)D and DNA damage (r = -0.0824; P > 0.05). No significant difference was seen across 25(OH)D tertiles: mean (SD) %DNA in comet tail/25(OH)D nmol/l values in lowest, middle and highest tertiles were, respectively, 18.64 (3.30)/31.6 (4.4), 18.90 (3.98)/42.9 (3.5), 18.19 (2.84)/59.9 (8.5), nor across the binary divide: 18.73 (3.63)% in <50nmol/l group vs. 18.27 (2.84)% in the >=50 nmol/l group. No association between vitamin D and oxidation-induced DNA damage was observed, but vitamin D deficiency was highly prevalent in the young adults studied, and we cannot rule out an ameliorative effect of correction of vitamin D deficiency on DNA damage. PMID- 27401997 TI - Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. AB - A fixed-dose tablet comprising the NS5A inhibitor ombitasvir, the NS3/4A inhibitor paritaprevir and ritonavir (ombitasvir/paritaprevir/ritonavir) (Technivie((r)), Viekirax((r))) is available for use, in combination with ribavirin, for the treatment of chronic hepatitis C virus (HCV) genotype 4 infection. High sustained virological response rates at 12 weeks post-treatment (SVR12) were achieved in treatment-naive or -experienced patients with chronic HCV genotype 4 infection, including patients without cirrhosis who received ombitasvir plus paritaprevir and ritonavir in combination with ribavirin for 12 weeks (SVR12 100 %) (PEARL-I trial), patients with compensated cirrhosis who received ombitasvir/paritaprevir/ritonavir plus ribavirin for 12 or 16 weeks (SVR12 97 and 98 %) (AGATE-I trial), or Egyptian patients without cirrhosis who received ombitasvir/paritaprevir/ritonavir plus ribavirin for 12 weeks (SVR12 94 %) or with compensated cirrhosis who received ombitasvir/paritaprevir/ritonavir plus ribavirin for 12 or 24 weeks (SVR12 97 and 93 %) (AGATE-II trial). Ombitasvir/paritaprevir/ritonavir was generally well tolerated in patients with chronic HCV genotype 4 infection without cirrhosis or with compensated cirrhosis in clinical trials. There have been postmarketing reports of hepatic decompensation and hepatic failure, which mainly occurred in patients with advanced cirrhosis who received regimens containing ombitasvir/paritaprevir/ritonavir. In conclusion, ombitasvir/paritaprevir/ritonavir is a valuable option for use in patients with chronic HCV genotype 4 infection without cirrhosis or with compensated cirrhosis. PMID- 27401998 TI - Erratum to Paraclostridium benzoelyticum gen. nov. sp. nov., isolated from marine sediment and reclassification of Clostridium bifermentans as Paraclostridium bifermentans comb. nov. Proposal of a new genus Paeniclostridium gen. nov. to accommodate Clostridium sordellii and Clostridium ghonii. PMID- 27401999 TI - A novel pattern mining approach for identifying cognitive activity in EEG based functional brain networks. AB - The complex nature of neuronal interactions of the human brain has posed many challenges to the research community. To explore the underlying mechanisms of neuronal activity of cohesive brain regions during different cognitive activities, many innovative mathematical and computational models are required. This paper presents a novel Common Functional Pattern Mining approach to demonstrate the similar patterns of interactions due to common behavior of certain brain regions. The electrode sites of EEG-based functional brain network are modeled as a set of transactions and node-based complex network measures as itemsets. These itemsets are transformed into a graph data structure called Functional Pattern Graph. By mining this Functional Pattern Graph, the common functional patterns due to specific brain functioning can be identified. The empirical analyses show the efficiency of the proposed approach in identifying the extent to which the electrode sites (transactions) are similar during various cognitive load states. PMID- 27402000 TI - Age at menarche and performance intelligence quotients of adolescents in Bangkok, Thailand: a cross-sectional study. AB - BACKGROUND: The presence of an association between age at the onset of puberty and intelligence quotient (IQ) in young adolescents remains controversial. The aim of this study was to explore the association between age at menarche and performance IQ scores of young female adolescents in Bangkok, Thailand. METHODS: A cross-sectional study was conducted among 537 students aged 11-15 years attending primary and secondary schools in the Dusit district of Bangkok, Thailand. The participants were selected based on two-step stratified sampling. Age at menarche and health and socioeconomic status were determined using a self report questionnaire completed by participants. Performance IQ scores were determined using the Standard Progressive Matrices intelligence test (Thai version) administered by registered clinical psychologists. RESULTS: Of the 537 participants, 0.4 had reached menarche at 8 years of age, 1.9 at 9 years, 10.1 at 10 years, 36.1 at 11 years, 37.6 at 12 years, 10.4 at 13 years, 3.4 at 14 years, and 0.2 % at 15 years. Age at menarche was inversely correlated with performance IQ (Pearson correlation -0.087, p = 0.047). The regression equation predicting performance IQ by age at menarche was performance IQ = 128.06 - 1.16*age at menarche (R (2) = 0.008). In univariate analysis, performance IQ was inversely correlated with age at menarche, body mass index (BMI), time spent watching television, and time sleeping, but was directly correlated with maternal age at birth (all p < 0.05). In multivariate analysis, age at menarche and BMI remained significantly inversely correlated with performance IQ (p < 0.05), while maternal age at birth was directly correlated with performance IQ. The model consisting of age at menarche, BMI, and maternal age at birth best predicted performance IQ. CONCLUSION: After adjusting for confounders, multiple regression analysis showed that age at menarche and BMI of young female adolescents living in the Dusit district of Bangkok, Thailand, were inversely correlated with performance IQ, whereas maternal age at birth was directly correlated with performance IQ. PMID- 27402003 TI - Relationship between pulmonary rehabilitation and care dependency in COPD. AB - : The aims of this study were to explore care dependency before and after pulmonary rehabilitation (PR) in patients with COPD (n=331) and to compare the response to PR between care dependent and independent patients. At baseline, 85 (25.7%) patients had a Care Dependency Scale (CDS) score <=68 points and were considered as care dependent. CDS scores of these patients improved after PR (p<0.001). After PR, CDS score of 38 (44.7%) patients with a baseline CDS score <=68 points increased to >68 points. Patients with a baseline CDS score <=68 points or >68 points showed after PR a comparable improvement in COPD Assessment Test, Hospital Anxiety and Depression Scale and 6-min walk distance (all p<0.05). TRIAL REGISTRATION NUMBER: NTR3416 (The Netherlands). PMID- 27402002 TI - Evaluation of safety and efficacy of noninvasive radiofrequency technology for submental rejuvenation. AB - Recently, a number of modalities have been used for noninvasive fat reduction. Radiofrequency (RF) technology is a promising tool for noninvasive body and face contouring. The aim of this study is to evaluate the efficacy and safety of novel noninvasive RF technology for the reduction of submental fat with 6 months of follow-up. Twenty-one subjects with submental fat accumulation were treated twice at 1-month intervals with monopolar RF, which could also be used to monitor real time temperature. The submental fat thickness and the circumference were evaluated with ultrasonography and a tape measure, respectively, at baseline followed by 1 and 6 months after the last treatment (0, 2, and 7 months). Pain and adverse effects were documented through a questionnaire. The submental circumference and thickness showed a statistically significant reduction after treatments. There was no subject who was not satisfied with the treatment and a physician's assessment showed that 82.3 and 52.9 % of patients showed above mild improvement at 2 and 7 months. The mean pain score corresponded with discomfort or moderate pain. There were no significant adverse effects such as scars or hyper/hypopigmentation. A novel noninvasive RF technology is shown to be effective and safe for submental fat reduction. The effectiveness of fat reduction was maintained for 6 months after the last treatment. PMID- 27402005 TI - Integrated pharmacokinetic-pharmacodynamic modelling to evaluate antimicrobial prophylaxis in abdominal surgery. AB - OBJECTIVES: To use Monte Carlo simulation with an integrated pharmacokinetic pharmacodynamic (PK-PD) model to evaluate guideline-recommended antimicrobial prophylaxis (AP) regimens with anaerobic coverage in abdominal surgery. METHODS: AP regimens were tested in simulated subjects undergoing elective abdominal surgery using relevant PK models and pathogen distributions in surgical site infections (SSIs). Predicted cumulative target attainment was the percentage of simulated subjects with free (unbound) antimicrobial plasma concentrations above the MICs for potential SSI pathogens. RESULTS: Cefazolin plus metronidazole covered SSI aerobes in 70% and the Bacteroides fragilis group in 99% of subjects, whereas cefoxitin only covered aerobes and anaerobes in 63% and 27% of cases, respectively. The broad-spectrum ceftriaxone plus metronidazole covered aerobes in 82% and anaerobes in 99% of simulations, while ertapenem covered aerobes in 88% and anaerobes in 90% of cases. Clindamycin covered the B. fragilis group in only 11% of cases. For cefazolin, 2 g doses maintained target attainment in simulated subjects from 80 to 120 kg, whereas 1 g doses were associated with lower target attainment against potential Gram-negative pathogens even in those <80 kg. For gentamicin, 3 mg/kg doses were comparable to the suggested 5 mg/kg, but superior to the traditional 1.5 mg/kg. CONCLUSIONS: This study demonstrates the use of PK-PD to inform decisions regarding AP in abdominal surgery. In this case, the findings support avoiding cefoxitin, avoiding clindamycin for anaerobic coverage, selecting 2 g doses of cefazolin even in patients <80 kg and using 3 mg/kg doses of gentamicin. PMID- 27402004 TI - The Use of Cervical Auscultation to Predict Oropharyngeal Aspiration in Children: A Randomized Controlled Trial. AB - In this study, we aimed to determine if the use of cervical auscultation (CA) as an adjunct to the clinical feeding evaluation (CFE + CA) improves the reliability of predicting oropharyngeal aspiration (abbreviated to aspiration) in children. The design of the study is based on open label, randomized controlled trial with concealed allocation. Results from children (<18 years) randomized to either CFE or CFE + CA were compared to videofluoroscopic swallow study (VFSS), the reference standard data. Aspiration was defined using the Penetration-Aspiration Scale. All assessments were undertaken at a single tertiary pediatric hospital. 155 children referred for a feeding/swallowing assessment were randomized into the CFE n = 83 [38 males; mean age = 34.9 months (SD 34.4)] or CFE + CA n = 72 [43 males; mean age = 39.6 months (SD 39.3)] group. kappa statistic, sensitivity, and specificity values, area under receiver operating curve (aROC). No significant differences between groups were found, although CFE + CA (kappa = 0.41, 95 % CI 0.2-0.62) had higher agreement for aspiration detection by VFSS, compared to the clinical feeding exam alone (kappa = 0.31, 95 % CI 0.10-0.52). Sensitivity was 85 % (95 % CI 62.1-96.8) for CFE + CA and 63.6 % (95 % CI 45.1 79.6) for CFE. aROC was not significantly greater for CFE + CA (0.75, 95 % CI 0.65-0.86) than CFE (0.66, 95 % CI 0.55-0.76) across all age groups. Although using CA as an adjunct to the clinical feeding evaluation improves the sensitivity of predicting aspiration in children, it is not sensitive enough as a diagnostic tool in isolation. Given the serious implications of missing the diagnosis of aspiration, instrumental assessments (e.g., VFSS), remain the preferred standard. PMID- 27402007 TI - In vitro activity of surotomycin against contemporary clinical isolates of toxigenic Clostridium difficile strains obtained in Spain. PMID- 27402006 TI - Virological efficacy of PI monotherapy for HIV-1 in clinical practice. AB - BACKGROUND: Clinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied. METHODS: An observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports. Survival analysis techniques were used to examine the times to virological failure and treatment discontinuation. RESULTS: Ninety-five patients had PI monotherapy treatment for a median duration of 126 weeks. Virological failure occurred during 64% of episodes and 8% of patients developed emergent protease mutations. We estimate failure occurs in half of episodes within 2 years following initiation. Where PI monotherapy was continued following virological failure, 68% of patients achieved viral re-suppression. Despite a high incidence of virological failure, many patients continued PI monotherapy and 79% of episodes were ongoing at the end of the study. The type of PI used, the presence of baseline protease mutations and the plasma HIV RNA at initiation did not have a significant impact on treatment outcomes. CONCLUSIONS: There was a higher incidence of virological failure and emerging resistance in our UK clinical setting than described in PI monotherapy clinical trials and other European observational studies. Despite this, many patients continued PI monotherapy and regained viral suppression, indicating this strategy remains a viable option in certain individuals following careful clinical evaluation. PMID- 27402008 TI - Resistance gene naming and numbering: is it a new gene or not?-authors' response. PMID- 27402009 TI - IFN-free therapy for HIV/HCV-coinfected patients within the liver transplant setting. AB - OBJECTIVES: IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV coinfected liver transplant recipients, the results are even poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting. METHODS: Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT [fibrosing cholestatic hepatitis (n = 1), fibrosis stage >=F3 (n = 2) and decompensated cirrhosis (n = 4)]. Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks. RESULTS: Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events. CONCLUSIONS: IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population. PMID- 27402011 TI - Structural and sequence analysis of class A beta-lactamases with respect to avibactam inhibition: impact of Omega-loop variations. AB - BACKGROUND: There exists a significant diversity among class A beta-lactamases and the proliferation of these enzymes is a significant medical concern due to the ability of some members to efficiently hydrolyse both extended-spectrum cephalosporins and carbapenems. Avibactam is a novel non-beta-lactam beta lactamase inhibitor that, in combination with ceftazidime, has recently obtained regulatory approval in the USA. Although avibactam is known to efficiently inhibit key class A enzymes, the diversity of this enzyme family warranted a more complete investigation to understand the breadth of the potential spectrum of inhibition. METHODS: Using the known residues critical for avibactam binding, a thorough structural and sequence-based conservation analysis was performed across >650 class A enzymes. Several variations that had the potential to impact avibactam inhibition were observed and representative enzymes were cloned and expressed isogenically to evaluate the impact of these variations. RESULTS: The majority of the key residues involved in avibactam binding were well conserved across the different sub-families of class A beta-lactamases, although some differences were observed. The differences in the Omega-loop of PER enzymes were found to impact the ability of avibactam to effectively protect beta-lactams against hydrolysis. However, substitutions in a key hydrogen-bonding residue (N170) in some of the GES variants were found to not have a significant impact on avibactam inhibition. CONCLUSIONS: Overall, the computational and experimental analyses suggest that the vast majority of class A beta-lactamases should be well inhibited by avibactam, although a very small number of outliers exist. PMID- 27402010 TI - Positive regulation of the Candida albicans multidrug efflux pump Cdr1p function by phosphorylation of its N-terminal extension. AB - OBJECTIVES: Overexpression of ATP-binding cassette (ABC) transporters is a frequent cause of multidrug resistance in cancer cells and pathogenic microorganisms. One example is the Cdr1p transporter from the human fungal pathogen Candida albicans that belongs to the pleiotropic drug resistance (PDR) subfamily of ABC transporters found in fungi and plants. Cdr1p is overexpressed in several azole-resistant clinical isolates, causing azole efflux and treatment failure. Cdr1p appears as a doublet band in western blot analyses, suggesting that the protein is post-translationally modified. We investigated whether Cdr1p is phosphorylated and the function of this modification. METHODS: Phosphorylated residues were identified by MS. Their function was investigated by site-directed mutagenesis and expression of the mutants in a C. albicans endogenous system that exploits a hyperactive allele of the Tac1p transcription factor to drive high levels of Cdr1p expression. Fluconazole resistance was measured by microtitre plate and spot assays and transport activity by Nile red accumulation. RESULTS: We identified a cluster of seven phosphorylated amino acids in the N-terminal extension (NTE) of Cdr1p. Mutating all seven sites to alanine dramatically diminished the ability of Cdr1p to confer fluconazole resistance and transport Nile red, without affecting Cdr1p localization. Conversely, a Cdr1p mutant in which the seven amino acids were replaced by glutamate was able to confer high levels of fluconazole resistance and to export Nile red. CONCLUSIONS: Our results demonstrate that the NTE of Cdr1p is phosphorylated and that NTE phosphorylation plays a major role in regulating Cdr1p and possibly other PDR transporter function. PMID- 27402012 TI - Impact of a Vitamin D Protocol in Pregnancy at an Urban Women's Health Clinic. AB - BACKGROUND: Adequate vitamin D levels are important during pregnancy for maternal and fetal health. The prevalence of vitamin D deficiency and appropriate treatment during pregnancy are not well documented. OBJECTIVES: This study aims to identify the prevalence of vitamin D deficiency in pregnant women and analyze the impact of a vitamin D protocol on achieving sufficient vitamin D levels. METHODS: A retrospective chart review was conducted among 200 women who received prenatal care between April 1, 2011, and December 1, 2012 (preprotocol) and July 1, 2013, and June 30, 2014 (postprotocol). In each sample period, 100 women were included. Women were included if they had 2 vitamin D levels drawn during pregnancy. Maternal age, ethnicity, vitamin D levels, gestational age at each level, and the status of vitamin D supplement were controlled for. RESULTS: Women in the preprotocol group achieving sufficiency (25[OH]D >= 30 ng/mL) increased from 43% to 60%. In the postprotocol group, sufficiency increased from 19% to 69%. Adherence to the protocol dose was highest in women who were initially deficient (25[OH]D <= 20 ng/mL), and correlation between adherence to the protocol dose and achievement of sufficiency was also highest in the group of women who were initially deficient. CONCLUSIONS: Vitamin D deficiency was prevalent (25% total) in this population. Implementation of a clinic-wide protocol for vitamin D supplementation during pregnancy resulted in a nonsignificant increase in the percentage of women achieving vitamin D sufficiency. PMID- 27402014 TI - Left Ventricular Hypertrophy in Children with Hypertension: in Search of a Definition. AB - PURPOSE OF REVIEW: The purpose of this review is to provide background on the importance of left ventricular hypertrophy (LVH) in children with hypertension, to highlight various diagnostic modalities and measures for defining LVH, and to demonstrate the need for standardization and a consensus definition for LVH in the pediatric population. RECENT FINDINGS: There is no clear consensus among specialists performing echocardiograms and treating clinicians on the definition of LVH in children with hypertension. In fact, there is considerable variation in every step of the evaluation of pediatric LVH. There is variation in every step of the assessment of LVH in the pediatric population. This variation exists in imaging modality, the type of measurement used, the method of calculating left ventricular mass (LVM), the method of indexing LVM to body size, the normalization method for the index used, the reference data used, the inclusion of confounders, the implementation in clinical practice, and the format for echocardiography reporting. PMID- 27402013 TI - Device-Based Therapy for Drug-Resistant Hypertension: An Update. AB - Drug-resistant hypertension (RH) remains a significant and common cardiovascular risk despite the availability of multiple potent antihypertensive medications. Uncontrolled resistant hypertension contributes substantially to excessive cardiovascular and renal morbidity and mortality. Clinical and experimental evidence suggest that sympathetic nervous system over-activity is the main culprit for the development and maintenance of drug-resistant hypertension. Both medical and interventional strategies, targeting the sympathetic over-activation, have been designed in patients with hypertension over the past few decades. Minimally invasive, catheter-based, renal sympathetic denervation (RDN) and carotid baroreceptor activation therapy (BAT) have been extensively evaluated in patients with RH in clinical trials. Current trial outcomes, though at times impressive, have been mostly uncontrolled trials in need of validation. Device based therapy for drug-resistant hypertension has the potential to provide alternative treatment options to certain groups of patients who are refractory or intolerant to current antihypertensive medications. However, more research is needed to prove its efficacy in both animal models and in humans. In this article, we will review the evidence from recent renal denervation, carotid baroreceptor stimulation therapy, and newly emerged central arteriovenous anastomosis trials to pinpoint the weak links, and speculate on potential alternative approaches. PMID- 27402015 TI - A comparison of health state utility values associated with oral potentially malignant disorders and oral cancer in Sri Lanka assessed using the EQ-5D-3 L and the EORTC-8D. AB - BACKGROUND: It has been suggested that the EQ-5D-3 L preference-based measure of health outcome lacks sensitivity to discriminate between health states in cancer patients. An alternative approach is to use a disease (cancer) specific preference-based measure, such as the EORTC-8D. A limited number of comparisons have been made between generic and disease specific preference-based measures. The aim of this study was to compare the utility scores from the EQ-5D-3 L and the EORTC-8D in a group of patients with oral cancer or with oral potentially malignant disorders (OPMD). METHODS: Patients (n = 151) with OPMD or oral cancer were recruited consecutively from six hospitals in Sri Lanka. All participants completed both the EQ-5D-3 L and the EORTC's QLQC-30 instrument. The Sri Lankan EQ-5D-3 L and EORTC-8D scoring algorithms were employed to estimate utility scores. The utility scores from the two instruments were compared for discrimination, responsiveness and correlation. RESULTS: There were significant differences across the two utility scores. The EQ-5D-3 L showed better discrimination than EORTC-8D with higher effect sizes. There were higher ceiling effects observed in the EQ-5D-3 L. There was poor correlation between the dimensions of the two instruments except for the mobility and physical functions. CONCLUSION: The two instruments captured different aspects of quality of life. The EQ-5D-3 L demonstrated better discrimination than the EORTC-8D. In mild conditions EORTC-8D was more responsive and we recommend further validation of this instrument in diverse cancer conditions. PMID- 27402016 TI - Clinical effects of a standardized Chinese herbal remedy, Qili Qiangxin, as an adjuvant treatment in heart failure: systematic review and meta-analysis. AB - BACKGROUND: Qili Qiangxin capsule is a standardized Chinese herbal treatment that is commonly used in China for heart failure (HF) alongside conventional medical care. In 2014, Chinese guidelines for the treatment of chronic HF highlighted Qili Qiangxin capsules as a potentially effective medicine. However, there is at present no high quality review to evaluate the effects and safety of Qili Qiangxin for patients with HF. METHODS: We conducted a systematic review and meta analysis and followed methods described in our registered protocol [PROSPERO registration: CRD42013006106]. We searched 6 electronic databases to identify randomized clinical trials (RCTs) irrespective of blinding or placebo control of Qili Qiangxin used as an adjuvant treatment for HF. RESULTS: We included a total of 129 RCTs published between 2005 and 2015, involving 11,547 patients, aged 18 to 98 years. Meta-analysis showed no significant difference between Qili Qiangxin plus conventional treatment and conventional treatment alone for mortality (RR 0.53, 95 % CI 0.27 to 1.07). However, compared with conventional treatment alone, Qili Qiangxin plus conventional treatment demonstrated a significant reduction in major cardiovascular events (RR 0.46, 95 % CI 0.34 to 0.64) and a significant reduction in re-hospitalization rate due to HF (RR 0.49, 95 % CI 0.38 to 0.64). Qili Qiangxin also showed significant improvement in cardiac function measured by the New York Heart Association scale (RR 1.38, 95 % CI 1.29 to 1.48) and quality of life as measured by Minnesota Living with Heart Failure Questionnaire (MD 8.48 scores, 95 % CI -9.56 to -7.39). There were no reports of serious adverse events relating to Qili Qiangxin administration. The majority of included trials were of poor methodological quality. CONCLUSIONS: When compared with conventional treatment alone, Qili Qiangxin combined with conventional treatment demonstrated a significant effect in reducing cardiovascular events and re-hospitalization rate, though not in mortality. It appeared to significantly improve quality of life in patients with HF and data from RCTs suggested that Qili Qiangxin is likely safe. This data was drawn from low quality trials and the results of this review must therefore be interpreted with caution. Further research is warranted, ideally involving large, prospective, rigorous trials, in order to confirm these findings. PMID- 27402017 TI - Allelic and Epitopic Characterization of Intra-Kidney Allograft Anti-HLA Antibodies at Allograft Nephrectomy. AB - The reasons for the increased incidence of de novo anti-human leukocyte antibody (HLA) donor-specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti-HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid-phase assays, anti-HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti-HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti-HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti-HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti-HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level. PMID- 27402018 TI - Serum macrophage migration inhibitory factor levels are associated with infarct volumes and long-term outcomes in patients with acute ischemic stroke. AB - PURPOSE: Previous studies have shown that macrophage migration inhibition factor (MIF) plays a significant role in stroke. The aim of this study was to investigate the association of the serum MIF level with both infarct volume and long-term outcome in patients with acute ischemic stroke (AIS). METHODS: This study included 146 patients who were identified within 24 h of first experiencing AIS symptoms. Serum MIF levels were tested at the time of admission and three months later. Logistic regression was used to evaluate the risk and long-term outcome of stroke according to serum MIF level. RESULTS: Serum MIF levels were only higher in acute-stage AIS patients compared with those of the normal controls (p < 0.0001). Chronic-stage serum MIF levels were significantly lower than acute-stage serum MIF levels (p < 0.001) and were similar to serum MIF levels in the controls (p = 0.392). The serum MIF level was positively associated with infarct volume (r = 0.5515, p < 0.0001) and NIHSS score (r = 0.5190, p < 0.0001). After adjusting for other significant outcome predictors, the serum MIF level was an independent predictor of long-term outcome, with an adjusted OR of 1.113 (p = 0.005, 95% CI: 1.051-1.238). CONCLUSIONS: This study demonstrated that serum MIF levels were significantly increased after AIS. Serum MIF levels at admission were positively correlated with infarct volume and long-term outcome in patients with AIS. The serum MIF level could serve as a useful prognostic marker in patients with AIS. PMID- 27402019 TI - Improving the quality of obstetric care for women with obstructed labour in the national referral hospital in Uganda: lessons learnt from criteria based audit. AB - BACKGROUND: Obstructed labour remains a major cause of maternal morbidity and mortality whose complications can be reduced with improved quality of obstetric care. The objective was to assess whether criteria-based audit improves quality of obstetric care provided to women with obstructed labour in Mulago hospital, Uganda. METHODS: Using criteria-based audit, management of obstructed labour was analyzed prospectively in two audits. Six standards of care were compared. An initial audit of 180 patients was conducted in September/October 2013. The Audit results were shared with key stakeholders. Gaps in patient management were identified and recommendations for improving obstetric care initiated. Six standards of care (intravenous fluids, intravenous antibiotics, monitoring of maternal vital signs, bladder catheterization, delivery within two hours, and blood grouping and cross matching) were implemented. A re-audit of 180 patients with obstructed labour was conducted four months later to evaluate the impact of these recommendations. The results of the two audits were compared. In-depth interviews and focus group discussions were conducted among healthcare providers to identify factors that could have influenced the audit results. RESULTS: There was improvement in two standards of care (intravenous fluids and intravenous antibiotic administration) 58.9 % vs. 86.1 %; p < 0.001 and 21.7 % vs. 50.5 %; P < 0.001 respectively after the second audit. There was no improvement in vital sign monitoring, delivery within two hours or blood grouping and cross matching. There was a decline in bladder catheterization (94 % vs. 68.9 %; p < 0.001. The overall mean care score in the first and second audits was 55.1 and 48.2 % respectively, p = 0.19. Healthcare factors (negative attitude, low numbers, poor team work, low motivation), facility factors (poor supervision, stock-outs of essential supplies, absence of protocols) and patient factors (high patient load, poor compliance to instructions) contributed to poor quality of care. CONCLUSION: Introduction of criteria based audit in the management of obstructed labour led to measurable improvements in only two out of six standards of care. The extent to which criteria based audit may improve quality of obstetric care depends on having basic effective healthcare systems in place. PMID- 27402020 TI - Self-reported reasons for treatment non-adherence in Chinese asthma patients: A 24-week prospective telephone follow-up study. AB - BACKGROUND: Treatment non-adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. OBJECTIVES: To evaluate treatment adherence and causes of non adherence in a large asthma Chinese population. To analyze newly-diagnosed patients' adherence first time. METHODS: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow-up phone calls were carried out for recording subjects' treatment adherence based on their self-reports. Subjects who reported non-adherence were additionally asked to choose the primary non adherence cause from a list of nine potential causes. RESULTS: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly-diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly-diagnosed patients were three times more likely to become non-adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30-39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non adherence was "relief of symptoms after short-term controller medication use" (43.8%). CONCLUSIONS: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population. PMID- 27402021 TI - Effect of hypoxia on cerebrovascular and cognitive function during moderate intensity exercise. AB - Exercise in hypoxia places added demands on the brain and cerebrovasculature that can impact cognitive function. The purpose of this study was to investigate the effect of acute hypoxia on cerebrovascular hemodynamics, markers of neuro steroidal modulation and brain-blood barrier (BBB) integrity, and cognition during exercise. Thirty healthy participants (21+/-4yrs., BMI 24.0+/-2.6kg?m(-2); 15 men) were randomized to both a~2.5h normoxic (FiO2 20.0%) and hypoxic (FiO2 12.5%) condition on two separate days. After 1.25h, participants underwent 10min of exercise-alone (cycling at 55% HRmax) and 15min of exercise+cognitive testing. Prefrontal cortex (PFC) tissue oxygenation and middle cerebral artery (MCA) mean blood velocity (MnV) were measured using near-infrared spectroscopy and transcranial Doppler respectively at rest, during exercise-alone, and during exercise+cognitive testing. Salivary levels of dehydroepiandosterone [DHEA], DHEA sulfate [DHEAS]) and neuron specific enolase (NSE) were measured pre and post exercise. Cognition was assessed using standard metrics of accuracy and reaction time (RT), and advanced metrics from drift-diffusion modeling across memory recognition, N-Back and Flanker tasks. MCA MnV increased from rest to exercise (p<0.01) and was unchanged with addition of cognitive testing during exercise in both normoxia and hypoxia. PFC oxygenation increased during exercise (p<0.05) and was further increased with addition of cognitive challenge in normoxia but decreased during exercise in hypoxia (p<0.05) with further reductions occurring with addition of cognitive tasks (p<0.05). DHEA and NSE increased and decreased post-exercise, respectively, in both normoxia and hypoxia (p<0.01). Accuracy on cognitive tasks was similar in normoxia compared to hypoxia, while RT was slower in hypoxia vs normoxia across memory recognition (p<0.01) and Flanker tasks (p=0.04). Drift-diffusion modeling suggested changes in memory RT were due to increases in caution (p<0.01). Overall cognitive performance is maintained during exercise in hypoxia concomitant with slower RT in select cognitive tasks and reduced oxygenation in the PFC. These changes were accompanied by slight increases in neuro-steroidal modulation but appear independent of changes in NSE, a biomarker of BBB integrity. Maintained accuracy and select increases in RT during hypoxic exercise may be related behavioral changes in caution. PMID- 27402022 TI - Stem cells display a donor dependent response to escalating levels of growth factor release from extracellular matrix-derived scaffolds. AB - Numerous growth factor delivery systems have been developed for tissue engineering. However, little is known about how the dose of a specific protein will influence tissue regeneration, or how different patients will respond to altered levels of growth factor presentation. The objective of the present study was to assess stem cell chondrogenesis within extracellular-matrix (ECM)-derived scaffolds loaded with escalating levels of transforming growth factor (TGF) beta3. It was also sought to determine if stem cells display a donor-dependent response to different doses of TGF-beta3, from low (5 ng) to high (200 ng), released from such scaffolds. It was found that ECM-derived scaffolds possess the capacity to bind and release increasing amounts of TGF-beta3, with between 60% and 75% of this growth factor released into the media over the first 12 days of culture. After seeding these scaffolds with human infrapatellar fat pad-derived stem cells (FPSCs), it was found that cartilage-specific ECM accumulation was greatest for the higher levels of growth factor loading. Importantly, soak loading cartilage ECM-derived scaffolds with high levels of TGF-beta3 always resulted in at least comparable levels of chondrogenesis to controls where this growth factor was continuously added to the culture media. Similar results were observed for FPSCs from all donors, although the absolute level of secreted matrix did vary from donor to donor. Therefore, while no single growth factor release profile will be optimal for all patients, the results of this study suggest that the combination of a highly porous cartilage ECM-derived scaffold coupled with appropriate levels of TGF-beta3 can consistently drive chondrogenesis of adult stem cells. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27402023 TI - County-level outcomes of a rural breast cancer screening outreach strategy: a decentralized hub-and-spoke model (BSPAN2). AB - Rural mammography screening remains suboptimal despite reimbursement programs for uninsured women. Networks linking non-clinical community organizations and clinical providers may overcome limited delivery infrastructure in rural areas. Little is known about how networks expand their service area. To evaluate a hub and-spoke model to expand mammography services to 17 rural counties by assessing county-level delivery and local stakeholder conduct of outreach activities. We conducted a mixed-method evaluation using EMR data, systematic site visits (73 interviews, 51 organizations), 92 patient surveys, and 30 patient interviews. A two-sample t test compared the weighted monthly average of women served between hub- and spoke-led counties; nonparametric trend test evaluated time trend over the study period; Pearson chi-square compared sociodemographic data between hub- and spoke-led counties. From 2013 to 2014, the program screened 4603 underinsured women. Counties where local "spoke" organizations led outreach activities achieved comparable screening rates to hub-led counties (9.2 and 8.7, respectively, p = 0.984) and did not vary over time (p = 0.866). Qualitative analyses revealed influence of program champions, participant language preference, and stakeholders' concerns about uncompensated care. A program that leverages local organizations' ability to identify and reach rural underserved populations is a feasible approach for expanding preventive services delivery. PMID- 27402024 TI - Incremental value of MRI for preoperative penile cancer staging. AB - PURPOSE: To evaluate the incremental value of magnetic resonance imaging (MRI), compared to clinical examination, for penile cancer (PC) local staging. MATERIALS AND METHODS: Twenty-five consecutive patients with histologically proven PC were evaluated prospectively. MRI staging was performed on 1.5 and 3.0T scanners using high-resolution T2 -weighted and postcontrast T1 -weighted images. Two blinded observers interpreted MR images. Clinical local staging was performed by experienced urologists. The pathology report was used as the standard of reference. RESULTS: The interobserver agreement for MRI staging, using a kappa test for T-staging was moderate, 0.52 (95% confidence interval [CI] = 0.24-0.78), P = 0.001, although a high correlation for N-staging, 0.72 (95% CI = 0.42-1.00), P = 0.001, was detected. Clinical staging was correct in 52.0% (13/25) of patients. After pathological staging, five (20.0%) lesions were upstaged and seven (28.0%) lesions were downstaged compared to clinical examination. MRI accurately defined T-staging in 18/25 lesions (72.0%). After pathologic staging, five (20.0%) were upstaged and two downstaged (8.0%), compared to MRI. Fifteen patients were submitted to inguinal and pelvic lymphadenectomy and considered for comparison of accuracy of nodal staging by physical examination and MRI. Clinical staging accurately staged 7/15 patients (46.7%). After histopathologic analysis, six cases had nodal staging upgraded and two cases were downgraded. MRI correctly staged 13/15 (86.7%). Using a chi-square for comparison, differences in proportion of corrected staging between clinical examination and MRI were not significant for T-staging (P = 0.14), but were significant for nodal staging (P = 0.02). CONCLUSION: According to our results, MRI improves local staging of PC patients, particularly for those with limited physical examination. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:118-124. PMID- 27402025 TI - Meanings for Sex and Commitment Among First Semester College Men and Women: A Mixed-Methods Analysis. AB - The purpose of this study was to replicate and extend research on the meanings for sex and commitment using a sample of first semester college students (N = 268). We examined responses to a series of open-ended questions about participants' meanings for sex and how they described these meanings as connected with relationship commitment. Our qualitative analyses replicated those of Olmstead, Billen, Conrad, Pasley, and Fincham (2013). Our largest group was the Committers (sex is indicative of love and trust and occurs after commitment is developed in a relationship), followed by Flexibles (sex can hold deep personal meaning, but can also be purely for pleasure and isn't always connected with commitment), and then Recreationers (sex is a basic need or purely for pleasure and is not associated with commitment). Groups were then examined based on demographic characteristics and pre-college hookup experience. Groups were found to differ by gender, relationship status and type, religiosity, and pre-college hookup experience. For example, a greater proportion of women than men were in the Committers group, whereas a greater proportion of men than women were in the Flexibles and Recreationers groups. Those in the Committers group had fewer pre college hookup partners than Flexibles and Recreationers; however, Flexibles and Recreationers did not differ in number of pre-college hookup partners. We then followed up (at the end of the semester) with a subsample (n = 73) of participants to examine whether meanings for sex and commitment remained stable or changed over a brief period of time. The majority (82.2 %) of participants' meanings remained stable. For those whose meanings shifted, meanings became more consistent with those of the Committers group than the other two groups. Implications for research and sexual and relationship education are discussed. PMID- 27402026 TI - Translation and Testing of the Swedish Version of Iceland-Family Perceived Support Questionnaire With Parents of Children With Congenital Heart Defects. AB - There is a need for a suitable instrument for the Swedish context that could measure family members' perceptions of cognitive and emotional support received from nurses. The purpose of this study was to translate and test the psychometric properties of the Swedish version of the Iceland-Family Perceived Support Questionnaire (ICE-FPSQ) and, further, to report perceptions of support from nurses by family members of children with congenital heart defects (CHDs). A sample of 97 parents of children with CHD, living in Sweden, completed the Swedish translation of ICE-FPSQ. The Swedish version of ICE-FPSQ was found to be reliable and valid in this context. Parents scored perceived family support provided by nurses working in pediatric outpatient clinics as low, which suggests that nurses in these outpatient contexts in Sweden offered family nursing only sparingly. PMID- 27402027 TI - Localized cortical thickening of the femoral diaphysis captured on an X-ray before alendronate therapy in two cases of atypical femoral fracture. AB - We herein report two cases of atypical femoral fracture (AFF). X-ray examinations at the first visit of these two female patients showed a complete fracture of the femoral diaphysis diagnosed as an atypical femoral fracture (AFF). X-rays of these two cases also showed localized cortical thickening of the femoral diaphysis. Both patients had been taking alendronate for more than 3 years because of postmenopausal osteoporosis. We assumed that both of the fractures were associated with the long-term use of alendronate. However, we retrospectively identified localized cortical thickening of the femoral diaphysis on an X-ray taken before the alendronate therapy in both of these cases. Therefore, we suspected a pathogenesis of AFFs in which preexisting stress or an insufficient fracture unrelated to bisphosphonate (BP) therapy and subsequent suppression of bone turnover due to BP administration led to the occurrence of an AFF. The patient underwent surgery using intramedullary nails in both of these cases, followed by the administration of teriparatide, and they were able to walk without any support at the final follow-up examination. PMID- 27402028 TI - The effect of Ramadan fasting on glycaemic control in insulin dependent diabetic patients: A literature review. AB - BACKGROUND: Ramadan fasting is one of the five pillars of Islam. People with diabetes are exempted from fasting according to Islamic rules. However, many people with diabetes wish to fast. Physicians are asked frequently by their patients about their ability to fast and the possible impact of fasting on their glycaemic control. Studies about the effect of Ramadan on people with insulin treated diabetes are scarce. This review aims to provide clinicians with the best recommendations for their patients with insulin-treated diabetes who wish to fast. METHODS: Four databases (Medline, EMBASE, Scopus and PubMed) were searched using the following MeSH terms and keywords: "insulin dependent diabetes mellitus", "type 1 diabetes mellitus", 'Ramadan' "and" "fasting". In addition, a hand search of key journals and reference lists was performed. Sixteen full text articles were selected for review and critical analysis. RESULTS: All of the included studies except one found improvement or no change in glycaemic control parameters during Ramadan fasting. The incidence of major complications were negligible. Minor hypoglycaemic events were reported in some studies but did not adversely affect fasting. Postprandial hyperglycaemia was a major concern in other studies. However, the incidence of severe hyperglycaemia and diabetic ketoacidosis were trivial. CONCLUSION: Ramadan fasting is feasible for insulin dependent diabetic patient who wish to fast. Clinicians should advise their patients about the importance of adequate glycaemic control before Ramadan and frequent glucose monitoring during fasting. Certain types of Insulin seem to be more beneficial than other. PMID- 27402029 TI - Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer. AB - INTRODUCTION: Nanocarriers have emerged as a powerful alternative for cancer therapy. Indeed, they are promising candidates to tackle the acquired resistance of surviving cells against antiproliferative drugs - the so-called multidrug resistance (MDR) phenomenon - which has arisen as one of the major clinical issues of chemotherapy. Among nanocarriers, this review focuses on the recent approaches based on tailored mesoporous silica nanoparticles (MSNs) that could overcome this problem. Areas covered: Herein we summarize the current efforts developed to provide MSN-based nanosystems of enhanced dual therapeutic action against diseased cells. This can be accomplished by three main approaches: i) increasing nanosystems' killing capability towards particular cells by enhancing both recognition and specificity; ii) increasing the apoptotic effect throughout co-delivery of several drugs; or iii) combining drug delivery with apoptosis induced by physical methods. Expert opinion: The development of multifunctional nanosystems able to exert the optimal therapeutic action through the minimal administration constitutes a major challenge in nanomedicine. Recent developments in advanced MSN-based platforms for drug delivery represent promising avenues in the management of MDR associated with cancer therapy. All strategies discussed in this manuscript demonstrate improvements against difficult-to-treat tumors. PMID- 27402030 TI - Retraction: Atomic-scale simulation to study the dynamical properties and local structure of Cu-Zr and Ni-Zr metallic glass-forming alloys. AB - Retraction of 'Atomic-scale simulation to study the dynamical properties and local structure of Cu-Zr and Ni-Zr metallic glass-forming alloys' by M. H. Yang et al., Phys. Chem. Chem. Phys., 2016, 18, 7169-7183. PMID- 27402033 TI - In this Issue. PMID- 27402031 TI - Canine acute leukaemia: 50 cases (1989-2014). AB - Acute leukaemia (AL) is a bone marrow malignancy of hematopoietic progenitors that historically is poorly responsive to treatment. With the widespread adoption of dose-intense chemotherapy, more human patients attain long-term survivals, but whether comparable progress has been made in canine AL is unknown. To investigate this question, medical records from three academic veterinary hospitals were reviewed. Fifty dogs met the criteria for AL, having excess circulating or marrow blasts, a major cytopenia(s), and no substantial lymphadenopathy. Thirty-six dogs received cytotoxic chemotherapy; 23 achieved a complete or partial response for a median of 56 days (range, 9-218). With failure or relapse, 14 dogs were rescued. Median survival with treatment was poor at 55 days (range, 1-300). Untreated (n = 6) and palliatively-treated (n = 8) dogs lived a median of 7.5 days. Most dogs developed chemoresistance within weeks of initiating treatment, and consequently, survival times for AL remain disappointingly short. PMID- 27402032 TI - Paradigmatic cases of pigmented lesions: How to not miss melanoma. AB - A large number of cases of melanoma exhibit clinical and dermoscopic clues leading to the correct diagnosis; however, sometimes melanoma can mimic benign melanocytic and non-melanocytic lesions. We present a small series of melanomas in which additional clues provided by confocal microscopy increased the index of suspicion and prompted us to perform an excisional biopsy. Practical rules that are useful in difficult-to-diagnose melanomas are discussed. PMID- 27402034 TI - Reflections. PMID- 27402035 TI - Celebrating achievements. PMID- 27402036 TI - Revisiting 'Effectiveness of problem-based learning curricula: theory, practice and paper darts'. PMID- 27402037 TI - Emotion sharing: implications for trainee doctor well-being. PMID- 27402038 TI - How to build a resilient surgeon: communities, cultures and complexity. PMID- 27402039 TI - Stereotypes and the hidden curriculum of students. PMID- 27402040 TI - Novel perspectives on health professionals' attitudes to disability. PMID- 27402041 TI - Mapping the dark matter of context: a conceptual scoping review. AB - CONTEXT: Like dark matter, the contexts for medical education are largely invisible to those within them, although context can have profound influences on teaching, learning and practice. For something that is so intrinsic to the field of medical education, the concept of context remains troubling to scholars and those running medical education programmes. This paper reports on a critical and conceptual review of the concept of context within the medical education literature and beyond. METHODS: A review was undertaken drawing on two sources: concepts of context in the medical education literature, and concepts of context across multiple academic disciplines. This body of material was iteratively, discursively and inductively synthesised. RESULTS: Few of the articles from the medical education literature described or defined context directly, tending instead to focus on describing specific elements of context, such as clinical disciplines, physical settings and political pressures, that could or did influence learning outcomes. The results were framed in terms of what context 'is', how context works (in terms of context-mechanism-outcome), and how context can be represented using patterns. The authors propose a definition of context in medical education, along with the means to model, contrast and compare different contexts based on recurring patterns. CONCLUSIONS: Context matters in medical education and it can, despite many challenges, be considered systematically and objectively. The findings from this study both represent a catalyst and challenge medical education researchers to look at context afresh. PMID- 27402042 TI - Dealing with emotions: medical undergraduates' preferences in sharing their experiences. AB - CONTEXT: Patient care evokes emotional responses such as uncertainty, grief and pride in medical students. There is a need for opportunities to share and express such emotions because they influence students' professional development and well being. There is a trend towards introducing mentor programmes into medical curricula. It remains unknown whether students are willing and able to share their emotional experiences within this formal setting. We set out to explore how medical students share their emotional experiences and why. METHODS: We used thematic analysis, including purposeful sampling, parallel processes of data collection and constant comparative analysis, maintaining an audit trail for validation purposes. The study had a constructivist, interactional design and used Goffman's dramaturgical theory as an interpretive framework. Nineteen students participated in individual, semi-structured interviews. RESULTS: Participants' narratives revealed a preference for sharing emotional experiences away from people who might expect them to uphold formal behaviour. They deliberately decided with whom to share their emotional experiences. Participants had a preference to talk to fellow students working in the same department, or family and friends outside medical school. CONCLUSIONS: Participants found it difficult to uphold behaviours that they thought patients, preceptors or the organisation expected of them as future doctors. In adjusting their behaviour to meet those expectations, they became attuned to how to best present themselves based on the people present. This influenced how they chose which emotional experiences to share with whom. PMID- 27402043 TI - Simulation-based education: understanding the socio-cultural complexity of a surgical training 'boot camp'. AB - OBJECTIVE: The focus of simulation-based education (SBE) research has been limited to outcome and effectiveness studies. The effect of social and cultural influences on SBE is unclear and empirical work is lacking. Our objective in this study was to explore and understand the complexity of context and social factors at a surgical boot camp (BC). METHODS: A rapid ethnographic study, employing the theoretical lenses of complexity and activity theory and Bourdieu's concept of 'capital', to better understand the socio-cultural influences acting upon, and during, two surgical BCs, and their implications for SBE. Over two 4-day BCs held in Scotland, UK, an observer and two preceptors conducted 81 hours of observations, 14 field interviews and 11 formal interviews with faculty members (n = 10, including the lead faculty member, session leaders and junior faculty members) and participants (n = 19 core surgical trainees and early-stage residents). RESULTS: Data collection and inductive analysis for emergent themes proceeded iteratively. This paper focuses on three analytical themes. First, the complexity of the surgical training system and wider health care education context, and how this influenced the development of the BC. Second, participants' views of the BC as a vehicle not just for learning skills but for gaining 'insider information' on how best to progress in surgical training. Finally, the explicit aim of faculty members to use the Scottish Surgical Bootcamp to welcome trainees and residents into the world of surgery, and how this occurred. CONCLUSIONS: To the best of our knowledge, this is the first empirical study of a surgical BC that takes a socio-cultural approach to exploring and understanding context, complexities, uncertainties and learning associated with one example of SBE. Our findings suggest that a BC is as much about social and cultural processes as it is about individual, cognitive and acquisitive learning. Acknowledging this explicitly will help those planning similar enterprises and open up a new perspective on SBE research. PMID- 27402044 TI - Experiences of medical students who are first in family to attend university. AB - CONTEXT: Students from backgrounds of low socio-economic status (SES) or who are first in family to attend university (FiF) are under-represented in medicine. Research has focused on these students' pre-admission perceptions of medicine, rather than on their lived experience as medical students. Such research is necessary to monitor and understand the potential perpetuation of disadvantage within medical schools. OBJECTIVES: This study drew on the theory of Bourdieu to explore FiF students' experiences at one Australian medical school, aiming to identify any barriers faced and inform strategies for equity. METHODS: Twenty-two FiF students were interviewed about their backgrounds, expectations and experiences of medical school. Interviews were recorded, transcribed and analysed thematically. Findings illustrate the influence and interaction of Bourdieu's principal forms of capital (social, economic and cultural) in FiF students' experiences. RESULTS: The absence of health professionals within participants' networks (social capital) was experienced as a barrier to connecting with fellow students and accessing placements. Financial concerns were common among interviewees who juggled paid work with study and worried about expenses associated with the medical programme. Finally, participants' 'medical student' status provided access to new forms of cultural capital, a transition that was received with some ambivalence by participants themselves and their existing social networks. CONCLUSIONS: This study revealed the gaps between the forms of capital valued in medical education and those accessible to FiF students. Admitting more students from diverse backgrounds is only one part of the solution; widening participation strategies need to address challenges for FiF students during medical school and should enable students to retain, rather than subdue, their existing, diverse forms of social and cultural capital. Embracing the diversity sought in admissions is likely to benefit student learning, as well as the communities graduates will serve. Change must ideally go beyond medical programmes to address medical culture itself. PMID- 27402045 TI - Women in medical education: views and experiences from the Kingdom of Saudi Arabia. AB - CONTEXT: Although research from Western contexts suggests that considerable inequalities for female medical educators exist in the workplace, we do not yet know the views and experiences of women within non-Western contexts. By examining the influence of context, intersecting identities and language use, this study explores female medical educators' views and experiences of gender, career progression and leadership in academic medicine in the Kingdom of Saudi Arabia (KSA). METHODS: We conducted individual interviews employing narrative interviewing techniques with 25 female medical educators from five schools in the KSA (June to December 2014). Data were analysed using framework analysis and drew on intersectionality theory. RESULTS: Participants expressed their views and experiences of career progression, leadership and gendered workplace cultures. Women's experiences of career progression and leadership in the KSA were influenced by their gender and varied according to their career stage, work environment and specialty. Participants discussed the gendered organisational cultures of academic medicine in the KSA in terms of gender inequalities (e.g. females being overlooked for leadership positions), gender stereotypes (e.g. women perceived as more likely to take part in shared leadership) and gendered specialties (e.g. surgery being male dominated). We revealed women's more tacit understandings about gender, career progression and leadership by examining how they talk (e.g. metaphoric, pronominal and emotional talk). Finally, participants constructed multiple intersecting personal (e.g. female, mother and young) and professional identities (e.g. doctor, teacher and leader) for themselves through their narratives. CONCLUSION: This study provides important new insights into female medical educators' experiences of career progression and leadership in a non-Western context. Investment in the future of women's careers in the KSA through faculty development initiatives and equality and diversity policies is now essential to help close the gender gap. PMID- 27402046 TI - At sea with disability! Transformative learning in medical undergraduates voyaging with disabled sailors. AB - CONTEXT: Attitudinal objectives are difficult to formulate, teach and assess; yet good attitudes are fundamental to good practice. For instance, studies highlight negative attitudes to disability in the medical student community that contrast with the self-conceptions of disabled persons. This study was designed to better understand attitudinal learning, inadequately addressed by contemporary programmes, through the application of Mezirow's 'transformative learning theory' (TLT) to a novel educational intervention. METHODS: Participating students went to sea, for voyages of 5-7 days, in tall ships operated by the Jubilee Sailing Trust. Each student was buddied with another sailor living with disability. Disabilities included cerebral palsy, loss of sight, loss of limbs and paraplegia. Students recorded their experiences using audio diaries, written logs, formal voyage reports and art work and in post-voyage seminars. The data were analysed using interpretive phenomenological analysis, and the results are considered under five themes suggested by Mezirow. RESULTS: Sixteen students were recruited, with four students sailing on each of four separate voyages. Each student recorded audio-diary entries, which had a total duration of between 10 and 212 minutes. For seven of the 16 students, the five key elements of TLT were demonstrable, suggesting that transformative learning, as described by Mezirow, was occurring. Drawing on diverse qualitative data, insights into different aspects of this transformation are provided. CONCLUSIONS: TLT can be used to characterise, and thus design, educational interventions to meet attitudinal learning objectives. Students can be helped to discover their less helpful frames of reference. In safe environments these frames can be challenged and subjected to personal and communal reflection. Drawing on audio diaries and other evidence, and in answer to critiques of contemporary medical teaching on disability, we demonstrate such transformation in students 'at sea with disability', highlighting elements that could potentially be transferred to the mainstream curriculum. PMID- 27402047 TI - Is three a crowd in a general practice setting? A medical student's view. PMID- 27402048 TI - Methodological review: quality of randomized controlled trials in health literacy. AB - BACKGROUND: The growing move towards patient-centred care has led to substantial research into improving the health literacy skills of patients and members of the public. Hence, there is a pressing need to assess the methodology used in contemporary randomized controlled trials (RCTs) of interventions directed at health literacy, in particular the quality (risk of bias), and the types of outcomes reported. METHODS: We conducted a systematic database search for RCTs involving interventions directed at health literacy in adults, published from 2009 to 2014. The Cochrane Risk of Bias tool was used to assess quality of RCT implementation. We also checked the sample size calculation for primary outcomes. Reported evidence of efficacy (statistical significance) was extracted for intervention outcomes in any of three domains of effect: knowledge, behaviour, health status. Demographics of intervention participants were also extracted, including socioeconomic status. RESULTS: We found areas of methodological strength (good randomization and allocation concealment), but areas of weakness regarding blinding of participants, people delivering the intervention and outcomes assessors. Substantial attrition (losses by monitoring time point) was seen in a third of RCTs, potentially leading to insufficient power to obtain precise estimates of intervention effect on primary outcomes. Most RCTs showed that the health literacy interventions had some beneficial effect on knowledge outcomes, but this was typically for less than 3 months after intervention end. There were far fewer reports of significant improvements in substantive patient oriented outcomes, such as beneficial effects on behavioural change or health (clinical) status. Most RCTs featured participants from vulnerable populations. CONCLUSIONS: Our evaluation shows that health literacy trial design, conduct and reporting could be considerably improved, particularly by reducing attrition and obtaining longer follow-up. More meaningful RCTs would also result if health literacy trials were designed with public and patient involvement to focus on clinically important patient-oriented outcomes, rather than just knowledge, behaviour or skills in isolation. PMID- 27402049 TI - Association Between Sleep Characteristics and Incident Dementia Accounting for Baseline Cognitive Status: A Prospective Population-Based Study. AB - BACKGROUND: Although research has shown that sleep disorders are prevalent among people with dementia, the temporal relationship is unclear. We investigated whether atypical sleep characteristics were associated with incident dementia while accounting for baseline cognitive functioning. METHODS: Screening Across the Lifespan Twin (SALT) study participants were 11,247 individuals from the Swedish Twin Registry who were at least 65 years at baseline (1998-2002). Sleep and baseline cognitive functioning were assessed via the SALT telephone screening interview. Data on dementia diagnoses came from national health registers. Cox regression was performed to estimate hazard ratios for dementia. RESULTS: After 17 years of follow-up, 1,850 dementia cases were identified. Short (<=6 hours) and extended (>9 hours) time in bed (TIB) compared to the middle reference group (hazard ratio = 1.40, 95% confidence interval = 1.06-1.85; hazard ratio = 1.11, 95% confidence interval = 1.00-1.24, respectively) and rising at 8:00 AM or later compared to earlier rising (hazard ratio = 1.12, 95% confidence interval = 1.01 1.24) were associated with higher dementia incidence. Bedtime, sleep quality, restorative sleep, and heavy snoring were not significant predictors. Findings stratified by baseline cognitive status indicated that the association between short TIB and dementia remained in those cognitively intact at the start. CONCLUSIONS: Short and extended TIB and delayed rising among older adults predicted increased dementia incidence in the following 17 years. The pattern of findings suggests that extended TIB and late rising represent prodromal features whereas short TIB appeared to be a risk factor for dementia. PMID- 27402050 TI - Sarcopenia and Health Care Utilization in Older Women. AB - BACKGROUND: Although there are several consensus definitions of sarcopenia, their association with health care utilization has not been studied. METHODS: We included women from the prospective Study of Osteoporotic Fractures with complete assessment of sarcopenia by several definitions at the Study of Osteoporotic Fractures Year 10 (Y10) exam (1997-1998) who also had available data from Medicare Fee- For-Service Claims (N = 566) or Kaiser Encounter data (N = 194). Sarcopenia definitions evaluated were: International Working Group, European Working Group for Sarcopenia in Older Persons, Foundation for the NIH Sarcopenia Project, Baumgartner, and Newman. Hurdle models and logistic regression were used to assess the relation between sarcopenia status (the summary definition and the components of slowness, weakness and/or lean mass) and outcomes that included hospitalizations, cumulative inpatient days/year, short-term (part A paid) skilled nursing facility stay in the 3 years following the Y10 visit. RESULTS: None of the consensus definitions, nor the definition components of weakness or low lean mass, was associated with increased risk of hospitalization or greater likelihood of short-term skilled nursing facility stay. Women with slowness by any criterion definition were about 50% more likely to be hospitalized; had a greater rate of hospitalization days amongst those hospitalized; and had 1.8 to 2.1 times greater likelihood of a short-term skilled nursing facility stay than women without slowness. There was the suggestion of a protective association of low lean mass by the various criterion definitions on short-term skilled nursing facility stay. CONCLUSION: Estimated effects of sarcopenia on health care utilization were negligible. However, slowness was associated with greater health care utilization. PMID- 27402051 TI - Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with preterm prelabor rupture of membranes. AB - BACKGROUND: Preterm prelabor rupture of membranes is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm prelabor rupture of membranes is not broadly used in clinical practice, and therefore, a shift toward a noninvasive amniotic fluid sampling method is needed. OBJECTIVE: The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of-care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intraamniotic inflammation, and microbial-associated intraamniotic inflammation in patients with preterm prelabor rupture of membranes. STUDY DESIGN: A prospective cohort study was conducted in women with singleton gestation complicated by preterm prelabor rupture of membranes at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive polymerase chain reaction analysis. Intraamniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration >=745 pg/mL. RESULTS: Several results were obtained in this study. First, it was possible to perform the point of-care assessment of interleukin-6 in vaginal fluid in 92% of the women (141 of 153), and only those women were included in the analyses. Second, the rate of microbial invasion of the amniotic cavity and intraamniotic inflammation was 26% (36 of 141) and 19% (27 of 141), respectively. Microbial-associated intraamniotic inflammation was identified in 12% of the women (17 of 141). Third, a strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; P < .0001). Fourth, the presence of microbial invasion of the amniotic cavity, intraamniotic inflammation, or microbial-associated intraamniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. Fifth, a vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity (sensitivity of 53% [19 of 36], specificity of 89% [93 of 104], positive predictive value of 63% [19 of 30], negative predictive value of 85% [93 of 110], positive likelihood ratio of 5.0 [95% confidence interval, 2.5-9.5], and negative likelihood ratio of 0.5 [95% confidence interval, 0.4-0.8]); intraamniotic inflammation (sensitivity of 74% [20/27], specificity of 91% [104/114], positive predictive value of 67% [20 of 30], negative predictive value of 94% [104 of 111], positive likelihood ratio of 8.4 [95% confidence interval, 4.5-15.9], and negative likelihood ratio of 0.3 [95% confidence interval, 0.2 0.5]); and microbial-associated intraamniotic inflammation (sensitivity of 100% [17 of 17], specificity of 90% [111 of 124), positive predictive value of 57% [17 of 30], negative predictive value of 100% [111 of 111], positive likelihood ratio of 9.5 [95% confidence interval, 5.7-16.0], and negative likelihood ratio of 0). CONCLUSION: The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, noninvasive, and inexpensive method for the identification of intraamniotic inflammation and microbial-associated intraamniotic inflammation in preterm prelabor rupture of membranes pregnancies, showing good specificity and negative predictive value. PMID- 27402052 TI - A dynamic quality assessment tool for laparoscopic hysterectomy to measure surgical outcomes. AB - BACKGROUND: The current health care system has an urgent need for tools to measure quality. A wide range of quality indicators have been developed in an attempt to differentiate between high-quality and low-quality health care processes. However, one of the main issues of currently used indicators is the lack of case-mix correction and improvement possibilities. Case-mix is defined as specific (patient) characteristics that are known to potentially affect (surgical) outcome. If these characteristics are not taken into consideration, comparisons of outcome among health care providers may not be valid. OBJECTIVE: The objective of the study was to develop and test a quality assessment tool for laparoscopic hysterectomy, which can serve as a new outcome quality indicator. STUDY DESIGN: This is a prospective, international, multicenter implementation study. A web-based application was developed with 3 main goals: (1) to measure the surgeon's performance using 3 primary outcomes (blood loss, operative time, and complications); (2) to provide immediate individual feedback using cumulative observed-minus-expected graphs; and (3) to detect consistently suboptimal performance after correcting for case-mix characteristics. All gynecologists who perform laparoscopic hysterectomies were requested to register their procedures in the application. A patient safety risk factor checklist was used by the surgeon for reflection. Thereafter a prospective implementation study was performed, and the application was tested using a survey that included the System Usability Scale. RESULTS: A total of 2066 laparoscopic hysterectomies were registered by 81 gynecologists. Mean operative time was 100 +/- 39 minutes, blood loss 127 +/- 163 mL, and the complication rate 6.1%. The overall survey response rate was 75%, and the mean System Usability Scale was 76.5 +/- 13.6, which indicates that the application was good to excellent. The majority of surgeons reported that the application made them more aware of their performance, the outcomes, and patient safety, and they noted that the application provided motivation for improving future performance. CONCLUSION: We report the development and test of a real-time, dynamic, quality assessment tool for measuring individual surgical outcome for laparoscopic hysterectomy. Importantly, this tool provides opportunities for improving surgical performance. Our study provides a foundation for helping clinicians develop evidence-based quality indicators for other surgical procedures. PMID- 27402053 TI - Success of smoking cessation interventions during pregnancy. AB - BACKGROUND: Smoking during pregnancy is a modifiable risk factor associated with adverse pregnancy outcomes. Smoking during pregnancy has been shown to increase the risk of spontaneous abortion, prematurity, low birthweight, congenital malformations, and sudden infant death syndrome. Despite the fact that it is well known that smoking can lead to adverse pregnancy outcomes, 13-25% of pregnant women overall continue to smoke during this critical period. OBJECTIVE: The objective of the study was to evaluate the effect of gestational use of bupropion and nicotine patch replacement therapy on the risk of the following: (1) smoking cessation, (2) prematurity, and (3) small for gestational age. STUDY DESIGN: Women included in the Quebec Pregnancy Cohort who filled the annual autoadministered questionnaire between Jan. 1, 1998, and June 30, 2009, were studied. Smokers before gestation with a pregnancy resulting in a live birth comprised the study population. Three mutually exclusive study groups were formed among those who smoked at the beginning of pregnancy: gestational users of nicotine patch replacement therapy, bupropion, and smokers who did not use nicotine patch replacement therapy or bupropion. Rate of smoking cessation during pregnancy as well as the risk of prematurity and small for gestational age were studied. RESULTS: Of the 1288 women who met inclusion criteria, 900 were smokers, 72 were bupropion users, and 316 were nicotine patch replacement therapy users. Bupropion and nicotine patch replacement therapy use during pregnancy were associated with higher rates of smoking cessation: 81% in the bupropion group; 79% for nicotine patch replacement therapy; and 0% in those not using buproprion or nicotine patch replacement therapy. After discontinuing smoking cessation medications, 60% of bupropion users and 68% of nicotine patch replacement therapy users did not smoke again during and after pregnancy. Adjusting for potential confounders, nicotine patch replacement therapy use was associated with a lower risk of prematurity (adjusted odds ratio, 0.21, 95% confidence interval, 0.13 0.34), and small-for-gestational-age (adjusted odds ratio, 0.61, 95% confidence interval, 0.41-0.90) compared to smoking. Bupropion was associated with a lower risk of prematurity only (adjusted odds ratio, 0.12, 95% confidence interval, 0.03-0.50). CONCLUSION: Bupropion and nicotine patch replacement therapy have an impact on smoking cessation during and after pregnancy. Nicotine patch replacement therapy also decreased the risk of prematurity and small for gestational age. PMID- 27402054 TI - Prevalence and factors associated with coinfection of human papillomavirus and Chlamydia trachomatis in adolescents and young women. AB - BACKGROUND: Human papillomavirus and Chlamydia trachomatis share the same route of sexual transmission and possess similar risk factors, indicating that coinfection may act synergistically in the induction of epithelial cell abnormalities. OBJECTIVE: This study aimed to determine the prevalence of human papillomavirus and Chlamydia trachomatis in adolescents and young women and identify factors associated with coinfection. STUDY DESIGN: This cross-sectional study included 276 female participants, aged 15-24 years, who were sexually active. Interviews were conducted and cervical specimens were collected for cervical smears and molecular tests. All cervical specimens were tested for 27 human papillomavirus genotypes by polymerase chain reaction amplification and hybridization to a human papillomavirus linear array. Detection of Chlamydia trachomatis was performed by polymerase chain reaction using primers directed to the region encoding the cryptic plasmid. Bivariate and multivariate analyses were performed to evaluate the factors associated with coinfection with human papillomavirus and Chlamydia trachomatis. The odds ratio, the adjusted odds ratio, and the 95% confidence interval were calculated. RESULTS: The prevalence of infection by Chlamydia trachomatis and human papillomavirus was 9.1% (95% confidence interval, 5.61-12.4) and 47.1% (95% confidence interval, 41.0-53.2), respectively. The prevalence of coinfection with human papillomavirus and Chlamydia trachomatis was 5.8% (95% confidence interval, 3.3-9.2); coinfection with 1 human papillomavirus type was 3.3% (95% confidence interval, 1.5-6.1) and with multiple types was 2.5% (95% confidence interval, 1.0-5.2). The prevalence of cytological abnormalities was 12.3% (95% confidence interval, 8.6-16.79). Human papillomavirus infections of high oncogenic risk were more prevalent (85.4%). Factors independently associated with coinfection of human papillomavirus/Chlamydia trachomatis obtained by multivariate analysis were the initiation of sexual activity under 16 years of age with an an odds ratio of 4.9 (95% confidence interval, 1.0-23.63; P = .05) and cytological abnormalities with an odds ratio of 10.7 (95% confidence interval, 1.9-59.5; P = .01), which indicates there is risk for the detection of cytological abnormalities in adolescents and young women coinfected with human papillomavirus/Chlamydia trachomatis. CONCLUSION: The prevalence of coinfection among our study population was of a magnitude that warrants attention by public health services. Adolescents and young women should be monitored for Chlamydia trachomatis infection and vaccinated against human papillomavirus. The association between cytological abnormalities and coinfection with human papillomavirus and Chlamydia trachomatis indicates the potential synergistic role of these infections in carcinogenesis of the cervix. PMID- 27402055 TI - Immune memory in invertebrates. AB - Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming. PMID- 27402056 TI - Complement inhibition in C3 glomerulopathy. AB - C3 glomerulopathy (C3G) describes a spectrum of glomerular diseases defined by shared renal biopsy pathology: a predominance of C3 deposition on immunofluorescence with electron microscopy permitting disease sub classification. Complement dysregulation underlies the observed pathology, a causal relationship that is supported by well described studies of genetic and acquired drivers of disease. In this article, we provide an overview of the features of C3G, including a discussion of disease definition and a review of the causal role of complement. We discuss molecular markers of disease and how biomarkers are informing our evolving understanding of underlying pathology. Research advances are laying the foundation for complement inhibition as a targeted approach to treatment of C3G. PMID- 27402058 TI - Low-Intensity Extracorporeal Shock Waves Therapy (LI-ESWT) for the treatment of erectile dysfunction: Where do we stand? PMID- 27402057 TI - Host genotype and age shape the leaf and root microbiomes of a wild perennial plant. AB - Bacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant's genetic control over its microbiota is of great interest to crop breeders and evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots of Boechera stricta (Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome is evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments. PMID- 27402059 TI - Re: Alison J. Price, Ruth C. Travis, Paul N. Appleby, et al. Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls. Eur Urol 2016;70:941-51. PMID- 27402061 TI - Increase in Prostate Cancer Metastases at Radical Prostatectomy in the United States. PMID- 27402060 TI - Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302. AB - BACKGROUND: Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA 302 (chemotherapy-naive men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). OBJECTIVE: This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (>=75 yr) and younger (<75 yr) patient subgroups. DESIGN, SETTING, AND PARTICIPANTS: Data were collected at the final OS analysis (96% of expected death events). Subsequent therapy data were prospectively collected, while response and discontinuation data were collected retrospectively following discontinuation of the study drug. INTERVENTION: At the discretion of the investigator, 67% (365/546) of patients from the AA arm received subsequent treatment with one or more agents approved for mCRPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. RESULTS AND LIMITATIONS: Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed >=50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed >=50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. CONCLUSIONS: Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00887198. PATIENT SUMMARY: Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced prostate cancer whose disease progressed after treatment with abiraterone acetate. Older patients were less likely to be treated with subsequent therapy. PMID- 27402062 TI - STAT3 in Prostate Cancer: Whom Should We Treat and When? PMID- 27402063 TI - The prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel disease. AB - BACKGROUND: Faecal calprotectin, an established biomarker used to assess mucosal inflammation, has been shown to correlate with endoscopic activity in inflammatory bowel disease (IBD). Longitudinal monitoring of faecal calprotectin, however, has rarely been employed beyond assessment of therapy response and post hoc analyses of clinical trials. AIM: To study whether consecutive measurements of faecal calprotectin every third month are useful for monitoring patients with IBD in clinical remission. METHODS: Patients aged 18 years or older, with a known diagnosis of IBD in clinical remission, were prospectively studied. Patients provided faecal samples every third month and were prospectively followed until the first clinical relapse or the end of the 2-year follow-up period. Measurements (EK-CAL, Buhlmann Lab. AG, Switzerland) were done at the end of the study. A Cox model with time-dependent covariates was used for analysis. RESULTS: Among 104 patients, Crohn's disease (n = 49) and ulcerative colitis (n = 55), 37 had a relapse. A doubling of faecal calprotectin level between two consecutively collected samples was associated with a 101% increased risk of relapse (HR: 2.01; 95% CI: 1.53-2.65; P < 0.001). The relative risk of relapse attenuated with time (HR: 0.80; 95% CI: 0.75-0.86; P < 0.001), by a 20% decrease in risk of relapse per 3-month period since the sample was obtained. CONCLUSIONS: By consecutively measuring faecal calprotectin every third month, we quantified the risk of relapse related to faecal calprotectin change and observed attenuation of the risk across time. Our data suggest that longitudinal monitoring of faecal calprotectin is informative in predicting relapse in IBD. PMID- 27402065 TI - Synthesis and evaluation of a maltose-bonded silica gel stationary phase for hydrophilic interaction chromatography and its application in Ginkgo Biloba extract separation in two-dimensional systems. AB - Maltose covalently bonded to silica was prepared by using carbonyl diimidazole as a cross-linker and employed as a stationary phase for hydrophilic interaction liquid chromatography. The column efficiency and the effect of water content, buffer concentration, and pH value influenced on retention were investigated. The separation or enrichment selectivity was also studied with nucleosides, saccharides, amino acids, peptides, and glycopeptides. The results indicated that the stationary phase processed good separation efficiency and separation selectivity in hydrophilic interaction liquid chromatography mode. Moreover, a two-dimensional hydrophilic interaction liquid chromatography* reversed-phase liquid chromatography method with high orthogonality was developed to analyze the Ginkgo Biloba extract fractions. The development of this two-dimensional chromatographic system would be an effective tool for the separation of complex samples of different polarities and contents. PMID- 27402064 TI - Pharmacokinetic, Pharmacodynamic, and Safety Profile of a Novel Anti-CD28 Domain Antibody Antagonist in Healthy Subjects. AB - We report pharmacokinetics, pharmacodynamics, and safety of a novel anti-CD28 domain antibody antagonist (lulizumab pegol) in healthy subjects following single or multiple-dose administration. A minimal anticipated biological effect level approach was used to select a 0.01 mg starting dose for a single-ascending-dose (SAD), double-blind, first-in-human study. Part 1 included 9 intravenous (IV; 0.01-100 mg) and 3 subcutaneous (SC; 9-50 mg) doses or placebo. In part 2, a keyhole limpet hemocyanin (KLH) immunization was performed in 16 subjects/panel, who received 1 of 3 IV doses (9-100 mg) or placebo. In a double-blind, multiple ascending-dose (MAD) study, subjects received SC lulizumab 6.25 mg every 2 weeks, 12.5 mg weekly, 37.5 mg weekly, or placebo. Among 180 treated subjects, 169 completed the studies. Peak concentrations and areas under the curve from time 0 to infinity increased dose proportionally. Estimated SC bioavailability was 68.2%. Receptor occupancy of approximately >=80% was maintained for >=2 weeks at >=9-mg doses (SAD) and throughout the dosing interval (MAD). IV doses >=9 mg inhibited antibody production against KLH for 2 weeks. No significant cytokine or immune cell changes were observed. No immunogenicity responses persisted, and there was no correlation to adverse events. Headache occurred in 21 SAD and 4 MAD subjects receiving lulizumab; in the MAD study 5 lulizumab subjects experienced infections. Lulizumab IV or SC was safe at all doses studied, without evidence of cytokine release. PMID- 27402066 TI - Hormonal regulation of aquaporin 3: opposing actions of prolactin and cortisol in tilapia gill. AB - Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW). Accordingly, extensive Aqp3 immunoreactivity was localized to cell membranes of branchial epithelium in FW-acclimated animals. Upon transferring hypophysectomized tilapia to FW, we identified that a pituitary factor(s) is required for Aqp3 expression in FW. Replacement with ovine Prl (oPrl) was sufficient to stimulate Aqp3 expression in hypophysectomized animals held in FW, an effect blocked by coinjection with cortisol. Both oPrl and native tilapia Prls (tPrl177 and tPrl188) stimulated aqp3 in incubated gill filaments in a concentration-related manner. Consistent with in vivo responses, coincubation with cortisol blocked oPrl-stimulated aqp3 expression in vitro Our data indicate that Prl and cortisol act directly upon branchial epithelium to regulate Aqp3 in tilapia. Thus, within the context of the diverse actions of Prl on hydromineral balance in vertebrates, we define a new role for Prl as a regulator of Aqp expression. PMID- 27402068 TI - Avoiding ethics pitfalls in publishing: a perspective from COPE. AB - The mission of the Committee on Publication Ethics (COPE) is to promote integrity in research publication. COPE was started in 1997 with a small group of editors and now has a membership of more than 10 000. Throughout its history, COPE has provided a forum for discussion about ethical issues related to all aspects of scholarly publishing and developed resources to assist those who write, review, and edit scholarly work. This concise review provides examples of ethical issues related to authoring, reviewing, and editing scholarly manuscripts from the perspective of COPE. PMID- 27402069 TI - Contribution to the study of Acanthodactylus (Sauria: Lacertidae) mtDNA diversity focusing on the A. boskianus species group. AB - The Acanthodactylus boskianus species group includes three species (A. boskianus, A. nilsoni, and A. schreiberi) of unclear phylogeny and phylogeographic history. By sequencing fragments of two mtDNA genes and performing phylogenetic, demographic, and chronophylogenetic analyses, we aimed at identifying their phylogenetic relationships while unravelling their biogeographic history. The analyses indicated that A. boskianus is a species complex, while A. s. schreiberi and A. s. ataturi show, both, low intraspecific genetic diversity. From a biogeographic point of view, the ancestor of A. s. schreiberi colonized Cyprus from the Middle East through overseas dispersal during the Pleistocene, whereas A. s. ataturi is considered to be a relict of a previously wider distribution. PMID- 27402070 TI - Halifax doctor awarded $1.4 million in damages. PMID- 27402067 TI - Effect of heart failure on catecholamine granule morphology and storage in chromaffin cells. AB - One of the key mechanisms involved in sympathoexcitation in chronic heart failure (HF) is the activation of the adrenal glands. Impact of the elevated catecholamines on the hemodynamic parameters has been previously demonstrated. However, studies linking the structural effects of such overactivation with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not been previously reported. In this study, HF was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Five weeks after surgery, cardiac function was assessed by ventricular hemodynamics. HF rats showed increased adrenal weight and adrenal catecholamine levels (norepinephrine, epinephrine and dopamine) compared with sham-operated rats. Rats with HF demonstrated increased small synaptic and dense core vesicle in splanchnic adrenal synapses indicating trans-synaptic activation of catecholamine biosynthetic enzymes, increased endoplasmic reticulum and Golgi lumen width to meet the demand of increased catecholamine synthesis and release, and more mitochondria with dilated cristae and glycogen to accommodate for the increased energy demand for the increased biogenesis and exocytosis of catecholamines from the adrenal medulla. These findings suggest that increased trans-synaptic activation of the chromaffin cells within the adrenal medulla may lead to increased catecholamines in the circulation which in turn contributes to the enhanced neurohumoral drive, providing a unique mechanistic insight for enhanced catecholamine levels in plasma commonly observed in chronic HF condition. PMID- 27402071 TI - Hydroxychloroquine-induced retinopathy in a 57-year-old woman. PMID- 27402072 TI - Accessibility to physician offices a "significant problem". PMID- 27402073 TI - Gaining competence through social media. PMID- 27402074 TI - Isotope costs may rise during supply gap. PMID- 27402076 TI - Chronic spontaneous urticaria. PMID- 27402075 TI - Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies. AB - BACKGROUND: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. METHODS: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting >= 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. RESULTS: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. INTERPRETATION: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery. PMID- 27402078 TI - Tumor-Induced NETosis as a Risk Factor for Metastasis and Organ Failure. AB - A large proportion of cancer-related deaths are caused by thrombosis and general organ failure. One example is acute renal failure, a major cause of morbidity and mortality in cancer patients. Surprisingly, however, little is known about the situation in organs that are not targets for metastasis or affected by the primary tumor. Recently, neutrophil extracellular traps (NET) were implicated in tumor-induced effects on distant organs unaffected by the actual tumor cells. Formation of NETs (NETosis) was identified a decade ago as a mechanism by which the innate immune system protects us from infections, especially in situations with sepsis. NETs are formed when neutrophils externalize their nuclear DNA together with antimicrobial granule proteins and form a web-like structure that can trap and kill microbes. It is now becoming increasingly clear that NETs also form under noninfectious inflammatory conditions like cancer, thrombosis, autoimmunity, and diabetes and significantly contribute to disease development. The existence of NET-dissolving drugs like heparin and DNase I, already in clinical use, and recent development of specific inhibitors of protein-arginine deiminase 4 (PAD4), an enzyme required for NET formation, should enable clinical targeting of NETosis. Preventing NETosis in cancer could provide a strategy to counteract tumor-induced thrombosis and organ failure as well as to suppress metastasis. Cancer Res; 76(15); 4311-5. (c)2016 AACR. PMID- 27402077 TI - Workers' perceptions of climate change related extreme heat exposure in South Australia: a cross-sectional survey. AB - BACKGROUND: Occupational exposure to extreme heat without sufficient protection may not only increase the risk of heat-related illnesses and injuries but also compromise economic productivity. With predictions of more frequent and intense bouts of hot weather, workplace heat exposure is presenting a growing challenge to workers' health and safety. This study aims to investigate workers' perceptions and behavioural responses towards extreme heat exposure in a warming climate. METHODS: A cross-sectional questionnaire survey was conducted in 2012 in South Australia among selected outdoor industries. Workers' heat risk perceptions were measured in the following five aspects: concerns about heat exposure, attitudes towards more training, policy and guideline support, the adjustment of work habits, and degree of satisfaction of current preventive measures. Bivariate and multivariate logistic regression analyses were used to identify factors significantly associated with workers' heat perceptions. RESULTS: A total of 749 respondents participated in this survey, with a response rate of 50.9 %. A little more than half (51.2 %) of respondents were moderately or very much concerned about workplace heat exposure. Factors associated with workers' heat concerns included age, undertaking very physically demanding work, and the use of personal protective equipment, heat illness history, and injury experience during hot weather. Less than half (43.4 %) of the respondents had received heat-related training. Workers aged 25-54 years and those with previous heat-related illness/injury history showed more supportive attitudes towards heat-related training. The provision of cool drinking water was the most common heat prevention measure. A little more than half (51.4 %) of respondents were satisfied with the current heat prevention measures. About two-thirds (63.8 %) of respondents agreed that there should be more heat-related regulations and guidelines for working during very hot weather. More than two-thirds (68.8 %) of the respondents were willing to adjust their current work habits to adapt to the likely increasing extreme heat, especially those with previous heat illness experience. CONCLUSIONS: The findings suggest a need to strengthen workers' heat risk awareness and refine current heat prevention strategies in a warming climate. Further heat educational programmes and training should focus on those undertaking physically demanding work outdoors, in particular young workers and those over 55 years with low education levels. PMID- 27402079 TI - HTLV-1 Viral Factor HBZ Induces CCR4 to Promote T-cell Migration and Proliferation. AB - Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and other inflammatory diseases in infected individuals. However, a complete understanding of how HTLV-1 transforms T cells is lacking. Expression of the chemokine receptor CCR4 on ATL cells and HTLV-1-infected cells suggested the hypothesis that CCR4 may mediate features of ATL and inflammatory diseases caused by HTLV-1. In this study, we show that the constitutively expressed HTLV-1 bZIP factor (HBZ) encoded by HTLV-1 is responsible for inducing CCR4 and its ability to promote T-cell proliferation and migration. Ectopic expression of HBZ was sufficient to stimulate expression of CCR4 in human and mouse T cells. Conversely, HBZ silencing in ATL cell lines was sufficient to inhibit CCR4 expression. Mechanistic investigations showed that HBZ induced GATA3 expression in CD4(+) T cells, thereby activating transcription from the CCR4 promoter. In an established air pouch model of ATL, we observed that CD4(+) T cells of HBZ transgenic mice (HBZ-Tg mice) migrated preferentially to the pouch, as compared with those in nontransgenic mice. Migration of CD4(+) T cells in HBZ-Tg mice was inhibited by treatment with a CCR4 antagonist. Proliferating (Ki67(+)) CD4(+) T cells were found to express high levels of CCR4 and CD103. Further, CD4(+) T-cell proliferation in HBZ-Tg mice was enhanced by coordinate treatment with the CCR4 ligands CCL17 and 22 and with the CD103 ligand E-cadherin. Consistent with this finding, we found that ATL cells in clinical skin lesions were frequently positive for CCR4, CD103, and Ki67. Taken together, our results show how HBZ activates CCR4 expression on T cells to augment their migration and proliferation, two phenomena linked to HTLV-1 pathogenesis. Cancer Res; 76(17); 5068-79. (c)2016 AACR. PMID- 27402080 TI - miR-9 and miR-200 Regulate PDGFRbeta-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer. AB - Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRbeta has been identified as a key player of this process and is considered a promising target for breast cancer therapy. Thus, we aimed at investigating the role of miRNAs as a therapeutic approach to inhibit PDGFRbeta-mediated vasculogenic properties of TNBC, focusing on miR-9 and miR-200. In MDA-MB-231 and MDA-MB-157 TNBC cell lines, miR-9 and miR-200 promoted and inhibited, respectively, the formation of vascular-like structures in vitro Induction of endogenous miR-9 expression, upon ligand-dependent stimulation of PDGFRbeta signaling, promoted significant vascular sprouting of TNBC cells, in part, by direct repression of STARD13. Conversely, ectopic expression of miR-200 inhibited this sprouting by indirectly reducing the protein levels of PDGFRbeta through the direct suppression of ZEB1. Notably, in vivo miR-9 inhibition or miR-200c restoration, through either the generation of MDA-MB-231-stable clones or peritumoral delivery in MDA-MB-231 xenografted mice, strongly decreased the number of vascular lacunae. Finally, IHC and immunofluorescence analyses in TNBC specimens indicated that PDGFRbeta expression marked tumor cells engaged in vascular lacunae. In conclusion, our results demonstrate that miR-9 and miR-200 play opposite roles in the regulation of the vasculogenic ability of TNBC, acting as facilitator and suppressor of PDGFRbeta, respectively. Moreover, our data support the possibility to therapeutically exploit miR-9 and miR-200 to inhibit the process of vascular lacunae formation in TNBC. Cancer Res; 76(18); 5562-72. (c)2016 AACR. PMID- 27402082 TI - Government should think again about prioritising seven day NHS services, King's Fund says. PMID- 27402081 TI - RPL23 Links Oncogenic RAS Signaling to p53-Mediated Tumor Suppression. AB - The ribosomal protein (RP)-MDM2 interaction is a p53 response pathway critical for preventing oncogenic c-MYC-induced tumorigenesis. To investigate whether the RP-MDM2-p53 pathway is a broad antioncogenic mechanism, we crossed mice bearing an MDM2(C305F) mutation, which disrupts RPL11 binding to MDM2, with mice expressing an oncogenic Hras(G12V) transgene. Interestingly, the MDM2(C305F) mutant mice, which are hypersensitive to c-MYC-induced tumorigenesis, are not hypersensitive to oncogenic Hras(G12V)-induced tumorigenesis. Unlike c-MYC, which induces expression of RPL11, RAS overexpression leads to an increase in RPL23 mRNA and protein whereas RPL11 expression remains unchanged. The induction of RPL23 involves both MEK and PI3K signaling pathways and requires mTOR function. Increased expression of RPL23, which maintains binding to MDM2(C305F) mutant, correlates with increased p53 expression in MDM2(C305F) cells. Furthermore, RAS overexpression can induce p53 in the absence of p19ARF, and the induction can be abolished by downregulation of RPL23. Thus, although the RPL11-MDM2-p53 pathway coordinates with the p19ARF-MDM2-p53 pathway against oncogenic c-MYC-induced tumorigenesis, the RPL23-MDM2-p53 pathway coordinates with the p19ARF-MDM2-p53 pathway against oncogenic RAS-induced tumorigenesis. Cancer Res; 76(17); 5030-9. (c)2016 AACR. PMID- 27402084 TI - Editorial. PMID- 27402083 TI - Integrated analysis of mRNA, microRNA and protein in systemic lupus erythematosus specific induced pluripotent stem cells from urine. AB - BACKGROUND: In clinical practice, it is difficult to monitor the repeating relapse in patients who have been suffering from systemic lupus erythematosus (SLE). The underlying etiology remains largely unknown. METHODS: Aiming to understand the pathogenesis of SLE, a detailed study was conducted. Renal tubular cells-derived iPSCs were successfully obtained from the urine of SLE patients and healthy controls. With the purpose to identify simultaneous expression profiling of microRNA, mRNA and protein, Illumina HiSeqTM 2000 System and iTRAQ-coupled 2D LC-MS/MS analysis were utilized in systemic lupus erythematosus-specific induced pluripotent stem cells (SLE-iPSCs) and normal control-iPSCs (NC-iPSCs). The integration of multiple profiling datasets was realized since it could facilitate the identification of non-seed miRNA targets, as well as differentially expressed mRNAs and proteins. RESULTS: For this study, profiling datasets of 1099 differentially expressed mRNAs, 223 differentially expressed microRNAs and 94 differentially expressed proteins were integrated. In order to investigate the influence of miRNA on the processes of regulating mRNAs and proteins' levels, potential targets of differentially expressed mRNAs and proteins were predicted using miRanda, TargetScan and Pictar. Multiple profiling datasets were integrated to facilitate the identification of miRNA targets, as well as differentially expressed mRNAs and proteins. Through gene ontology (GO) analysis of differentially expressed mRNAs and proteins, biological processes that drive proliferation were identified, such as mRNA processing and translation. Western blot and Q-PCR confirmed AK4 protein and mRNA up-regulation. The findings also showed that TAGLN's protein and mRNA level were down-regulated in SLE-iPSCs, both miR-371a-5p and let-7a-5p in SLE-iPSC were down-regulated and verified using Q PCR. The up-regulation of AK4 involved in nucleotide biosynthesis suggested a general acceleration of anabolic metabolism induced by down-regulated miR-371a 5p, which might contribute to SLE. CONCLUSION: Based on high throughput analysis, integrated miRNA, mRNA, and protein expression data were generated. Differentially expressed dates were also adopted in conjunction with in-silico tools to identify potential candidates for SLE-iPSCs. Representative miRNA, mRNA and proteins were verified. It was also expected that the knowledge gained from this study can be applied to assess the usefulness of pathogenesis and novel biomarker candidates of SLE, which may develop a new way for SLE diagnosis. PMID- 27402085 TI - Small intestinal bacterial overgrowth is associated with irritable bowel syndrome and is independent of proton pump inhibitor usage. AB - BACKGROUND: Current knowledge suggests that small intestinal overgrowth participates in the pathogenesis of irritable bowel syndrome. It is questionable if this association is modulated by intake of proton pump inhibitors (PPIs). METHODS: In a prospective study, quantitative cultures of duodenal aspirates were performed for aerobic species in 897 consecutive patients undergoing upper GI tract endoscopy. SIBO was defined as equal to or more than 10(3) cfu/ml. The effect of PPI intake on the relationship between SIBO and IBS was the primary endpoint. RESULTS: Analysis among patients without any history of PPI intake (n = 713) showed that odds ratio (OR) for IBS in the event of SIBO was 5.63 (3.73 8.51, p < 0.0001); this was 4.16 (1.91-9.06) when analysis was done among patients with history of PPI intake (n = 184, p: 0.498 between patients without and with PPI intake). Multiple logistic regression analysis found that factors independently associated with SIBO were age above or equal to 60 years (OR: 2.36), body mass index more than or equal to 22 kg/m(2) (OR: 0.60), presence of IBS (OR: 6.29), type 2 diabetes mellitus (OR: 1.59) and gastritis (OR: 0.47). CONCLUSIONS: The association between IBS and SIBO was completely independent from PPI intake. Although gastritis was protective against SIBO, results show that PPI intake cannot prime SIBO. PMID- 27402086 TI - Changes in serum progesterone concentrations in Bernese mountain dogs and Cavalier King Charles Spaniels during pregnancy. AB - Progesterone (P4) concentrations during canine pregnancy follow a specific pattern. Although the general pattern is similar, it is likely that breed specific differences exist. Detailed knowledge about the physiological range of P4 concentrations may be helpful in cases of suspected hypoluteoidism. The aim of this study was to investigate P4 changes during pregnancy in a small and a large breed, to obtain reference values for specific intervals during pregnancy and to test for breed- or body weight-specific differences. We studied P4 concentrations in pregnancies from healthy Bernese mountain dogs (BMDs, n = 6) and Cavalier King Charles Spaniels (CKCSs, n = 6) with a normal reproductive history. Blood samples for P4 were taken to determine the day of ovulation and after confirmation of pregnancy in regular intervals from Days 23 to 29 to Days 60 to 64. Bernese mountain dogs delivered 6.2 +/- 2.6 puppies (range: 3-9) 63.4 +/- 1.5 (range: 61 65) days after ovulation (excluding data from one BMD with elective c-section) and CKCS delivered 3.3 +/- 1.9 puppies (range: 1-5) 63.5 +/- 1.1 (range: 62-65) days after ovulation. In general, the P4 concentrations of individual dogs continuously decreased from the first to the last sampling during pregnancy. Respective mean concentrations were Days 23 to 29: 19.2 +/- 4.3/22.2 +/- 3.9 ng/mL (BMD/CKCS), Days 30 to 34: 15.6 +/- 2.3/17.7 +/- 5.8 ng/mL, Days 35 to 39: 12.5 +/- 2.8/14.1 +/- 3.4 ng/mL, Days 40 to 44: 8.9 +/- 1.4/11.8 +/- 3.7 ng/mL, Days 45 to 49: 7.7 +/- 1.6/8.9 +/- 1.9 ng/mL, Days 50 to 54: 6.0 +/- 1.3/8.7 +/- 7.1 ng/mL, Days 55 to 59: 4.7 +/- 1.2/5.3 +/- 2.8 ng/mL, and Days 60 to 64: 3.69 +/- 1.86/2.62 +/- 0.42 ng/mL. ANOVA indicated significant differences over time within each breed when considered individually (P < 0.0001 each), but not between breeds although mean P4 was slightly lower in BMD until Days 55 to 59. The present data clearly confirm the previously described P4 pattern during canine pregnancy with highest P4 concentrations obtained in the first interval (Days 23 29) and a subsequent decrease of P4. The lack of a significant rapid prepartal P4 drop might be related to methodological issues (time of last collection in regards to parturition). Other than expected, we failed to proof significant differences in P4 between CKCS and BMD. Further studies are required to confirm the results on a larger population of both breeds, but also other large-sized breeds to test for the hypothesis if BMD might have lower P4 concentrations and smaller litter size compared to other large breeds with larger litter size. PMID- 27402087 TI - Relationship between the number of cells surrounding oocytes and energy states of oocytes. AB - Lipid content, ATP content, and histone acetylation are thought to reflect the energy state of cells. In addition, the energy state closely associates with growth and developmental ability of oocytes. Oocyte growth is accompanied by active proliferation of the surrounding granulosa cells (GCs), and GCs play a key role in the provision of energy substrates to the oocytes. In the present study, we first examined the relationship among the average number of GCs per follicle, the average number of cumulus cells (CCs) per oocyte, and the average lipid content in oocytes that developed in vivo within individual donor gilts. Second, we validated the relationship between the number of cells surrounding oocytes and the energy states of oocytes by using an IVC system of oocyte granulosa cell complexes (OGCs) derived from early antral follicles. We collected cumulus cells and oocyte complexes (COCs) from antral follicles (3-5 mm in diameter) and found that average lipid content in oocytes significantly correlated with the average number of both GCs/follicle and CCs/oocyte (P < 0.05). In the next series of experiments, we collected OGCs from early antral follicles (0.5-0.7 mm in diameter), and cultured them for 14 days, and then determined the cell number of OGCs, as well as the lipid content, ATP content, and acetylation level of H4K12 in oocytes grown in vitro. In addition, glucose consumption by OGCs was calculated from the sample media collected at Days 13 and 14. The lipid content of oocytes grown in vitro, significantly correlated with the number of cells surrounding the oocytes (P < 0.01) and with the level of glucose consumption by OGCs (P < 0.01). In addition, both ATP content and H4K12 acetylation levels of oocytes grown in vitro significantly correlated with the number of cells surrounding the oocytes (P < 0.05) and glucose consumption by OGCs (P < 0.05). In conclusion, the lipid content of oocytes depends on the number of cells surrounding the oocytes, and glucose uptake by OGCs is crucial for lipid content and ATP content, and H4K12 acetylation in oocytes. PMID- 27402088 TI - The H3 chaperone function of NASP is conserved in Arabidopsis. AB - Histones are abundant cellular proteins but, if not incorporated into chromatin, they are usually bound by histone chaperones. Here, we identify Arabidopsis NASP as a chaperone for histones H3.1 and H3.3. NASP interacts in vitro with monomeric H3.1 and H3.3 as well as with histone H3.1-H4 and H3.3-H4 dimers. However, NASP does not bind to monomeric H4. NASP shifts the equilibrium between histone dimers and tetramers towards tetramers but does not interact with tetramers in vitro. Arabidopsis NASP promotes [H3-H4]2 tetrasome formation, possibly by providing preassembled histone tetramers. However, NASP does not promote disassembly of in vitro preassembled tetrasomes. In contrast to its mammalian homolog, Arabidopsis NASP is a predominantly nuclear protein. In vivo, NASP binds mainly monomeric H3.1 and H3.3. Pulldown experiments indicated that NASP may also interact with the histone chaperone MSI1 and a HSC70 heat shock protein. PMID- 27402090 TI - Paenibacillus yunnanensis sp. nov., isolated from Pu'er tea. PMID- 27402089 TI - Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes. AB - Alexander disease is a fatal neurological illness characterized by white-matter degeneration and formation of Rosenthal fibers, which contain glial fibrillary acidic protein as astrocytic inclusion. Alexander disease is mainly caused by a gene mutation encoding glial fibrillary acidic protein, although the underlying pathomechanism remains unclear. We established induced pluripotent stem cells from Alexander disease patients, and differentiated induced pluripotent stem cells into astrocytes. Alexander disease patient astrocytes exhibited Rosenthal fiber-like structures, a key Alexander disease pathology, and increased inflammatory cytokine release compared to healthy control. These results suggested that Alexander disease astrocytes contribute to leukodystrophy and a variety of symptoms as an inflammatory source in the Alexander disease patient brain. Astrocytes, differentiated from induced pluripotent stem cells of Alexander disease, could be a cellular model for future translational medicine. PMID- 27402091 TI - GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review. AB - BACKGROUND: GM2 gangliosidosis-AB variants a rare autosomal recessive neurodegenerative disorder occurring due to deficiency of GM2 activator protein resulting from the mutation in GM2A gene. Only seven mutations in nine cases have been reported from different population except India. CASE PRESENTATION: Present case is a one year old male born to 3rd degree consanguineous Indian parents from Maharashtra. He was presented with global developmental delay, hypotonia and sensitive to hyperacusis. Horizontal nystagmus and cherry red spot was detected during ophthalmic examination. MRI of brain revealed putaminal hyperintensity and thalamic hypointensity with some unmyelinated white matter in T2/T1 weighted images. Initially he was suspected having Tay-Sachs disease and finally diagnosed as GM2 gangliosidosis, AB variant due to truncated protein caused by nonsense mutation c.472 G > T (p.E158X) in GM2Agene. CONCLUSION: Children with phenotypic presentation as GM2 gangliosidosis (Tay-Sachs or Sandhoff disease) and normal enzyme activity of beta-hexosaminidase-A and -B in leucocytes need to be investigated for GM2 activator protein deficiency. PMID- 27402093 TI - Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitor [18F]GSK2647544 in Healthy Male Subjects. AB - PURPOSE: GSK2647544 is a potent and specific inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), which was in development as a potential treatment for Alzheimer's disease (AD). In order to refine therapeutic dose predictions and confirm brain penetration, a radiolabelled form of the inhibitor, [18F]GSK2647544, was manufactured for use in a positron emission tomography (PET) biodistribution study. PROCEDURES: [18F]GSK2647544 was produced using a novel, copper iodide (Cu(I)) mediated, [18F]trifluoromethylation methodology. Healthy male subjects (n = 4, age range 34-42) received an oral dose of unlabelled GSK2647544 (100 mg) and after 2 h an intravenous (iv) injection of [18F]GSK2647544 (average injected activity and mass were 106 +/- 47 MBq and 179 +/- 55 MUg, respectively) followed by dynamic PET scans for 120 min. Defined regions of interest (ROI) throughout the brain were used to obtain regional time activity curves (TACs) and compartmental modelling analysis used to estimate the primary outcome measure, whole brain volume of distribution (VT). Secondary PK and safety endpoints were also recorded. RESULTS: PET dynamic data were successfully obtained from all four subjects and there were no clinically significant variations of the safety endpoints. Inspection of the TACs indicated a relatively homogenous uptake of [18F]GSK2647544 across all the ROIs examined. The mean whole brain VT was 0.56 (95 % CI, 0.41-0.72). Secondary PK parameters, Cmax (geometric mean) and Tmax (median), were 354 ng/ml and 1.4 h, respectively. Metabolism of GSK2647544 was relatively consistent across subjects, with 20-40 % of the parent compound [18F]GSK2647544 present after 120 min. CONCLUSIONS: The study provides evidence that GSK2647544 is able to cross the blood brain barrier in healthy male subjects leading to a measurable brain exposure. The administered doses of GSK2647544 were well tolerated. Exploratory modelling suggested that a twice-daily dose of 102 mg, at steady state, would provide ~80 % trough inhibition of brain Lp-PLA2 activity. TRIAL REGISTRATION: Clintrials.gov: NCT01924858. PMID- 27402094 TI - Management of tracheal chondrosarcoma almost completely obstructing the airway: a case report. AB - BACKGROUND: Primary malignant tracheal tumors account for only 0.2 % of all malignancies of the respiratory tract. Tracheal chondrosarcoma is a rare condition and only 17 cases have been described in the literature from 1965 to date. Herein we report the very unusual case of a patient with a tracheal chondrosarcoma, electively treated by curative surgery despite the virtually complete obstruction of the airway. CASE PRESENTATION: We present the case of a 79-year old Caucasian man with long-lasting wheezing misdiagnosed as asthma and affected by a tracheal chondrosarcoma almost completely obstructing the airway. Videobronchoscopy and imaging investigations revealed a well-circumscribed mass arising from the cartilaginous rings of the cervical trachea with a posterior residual respiratory space of about 1 mm. Because of the mobility and flaccidity of the uninvolved pars membranacea, the tiny respiratory space slightly expanded during inspiration and expiration allowing the patient to be treated without an essential emergency procedure. Standard tracheal intubation was impossible. Rigid bronchoscopy enabled placement of a small tracheal tube distally to the tumor. Successful cervical tracheal resection and reconstruction was then performed, achieving complete tumor excision. Histologically, the mass was characterized as a low-grade tracheal chondrosarcoma. Videobronchoscopy performed 9 months after surgery showed a wide, well healed tracheal anastomosis. Ten months after surgery, the patient is alive and disease free. CONCLUSION: Complete surgical resection is the treatment of choice for tracheal chondrosarcoma. Rigid bronchoscopy is an essential tool for diagnostic and therapeutic purposes. It allows the palliative maneuvers for obstruction relief but also, in resectable patients, the intraoperative safe and straightforward management of the obstructed airway. PMID- 27402092 TI - Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis. AB - PURPOSE: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [11C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated. PROCEDURES: Colitis was induced in rats by intra rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [11C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [11C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation. RESULTS: Eleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [11C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [11C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11. CONCLUSION: Inflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [11C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera. PMID- 27402095 TI - Robot-assisted laparoscopic versus open middle pancreatectomy: short-term results of a randomized controlled trial. AB - OBJECTIVE: This first prospective randomized controlled trial was performed to compare short-term outcomes of robot-assisted laparoscopic middle pancreatectomy (RA-MP) with open middle pancreatectomy (OMP). BACKGROUND: RA-MP is a novel minimally invasive surgical technique for benign or borderline tumors in the pancreatic neck or body. Its short-term effectiveness and safety remain unknown, compared to OMP. METHODS: Patients eligible for MP from August 2011 to November 2015 were randomized into the RA-MP or OMP group. The primary endpoint was length of hospital stay (LOS). Secondary endpoints were intraoperative parameters, and postoperative and recovery variables. RESULTS: A total of 100 patients were included into the study to analyze primary and secondary endpoints. Demographic characteristics and pathological parameters were similar in both groups. Furthermore, LOS was significantly shorter (15.6 vs. 21.7 days, P = 0.002), median operative time was reduced (160 vs. 193 min, P = 0.002), median blood loss was lower (50 vs. 200 mL, P < 0.001), rate of clinical postoperative pancreatic fistula (POPF) was lower (18 vs. 36.0 %, P = 0.043), nutritional status recovery was better, off-bed return to activity was expedited (3.1 vs. 4.6 days, P < 0.001), and resumption of bowel movement was faster (3.5 vs. 5.0 days, P < 0.001) in the RA-MP group, compared to the OMP group. CONCLUSION: RA-MP was associated with significantly shorter LOS, reduced operative time, blood loss and clinical POPF rate, and expedited postoperative recovery, compared to OMP. PMID- 27402097 TI - Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. AB - BACKGROUND: No online current list of potentially life-threatening, hepatotoxic herbs and dietary supplements based on PubMed case reports exists in a summarized tabular form. METHODS: Documented case reports of herbs or dietary supplements (DS; includes herbs) appearing to contribute to liver injury were used to create an online "DS Toxic Table" of potentially hepatotoxic herbs and dietary supplements (PubMed, 1966 to June, 2016, and cross-referencing). The spectrum of DS induced liver injuries (DSILI) included elevated liver enzymes, hepatitis, steatosis, cholestasis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, veno-occlusive disease, acute liver failure requiring a liver transplant, and death. RESULTS: Over the past 50 years, approximately 21 herbs (minus germander and usnic acid that are no longer sold) and 12 dietary supplements (minus the nine no longer sold and vitamin A & niacin due to excess intake) posed a possible risk for liver injures in certain individuals. The herbs with the most number of reported publications (but not cases studies) in descending order, were germander, black cohosh, kava extract, and green tea extract. CONCLUSION: These online DS Toxic Tables will contribute to continued Phase IV post marketing surveillance to detect possible liver toxicity cases and serve to forewarn consumers, clinicians, and corporations. PMID- 27402096 TI - Robot-assisted versus laparoscopic-assisted surgery for colorectal cancer: a meta analysis. AB - BACKGROUND AND OBJECTIVES: Robotic surgery is positioned at the cutting edge of minimally invasive management of colorectal cancer. We performed a meta-analysis of data from randomized controlled trials (RCTs) and non-RCTs (NRCTs) that compared the clinicopathological outcomes of robotic-assisted colorectal surgery (RACS) with those of laparoscopic-assisted colorectal surgery (LACS). Inferences on the feasibility and the relative safety and efficacy have been drawn. METHODS: A literature search for relevant studies was performed on MEDLINE, Ovid, Embase, Cochrane Library, and Web of Science databases. Inter-group differences in the standardized mean differences and relative risk were assessed. Operation times, conversion rates to open surgery, estimated blood loss (EBL), early postoperative morbidity, and length of hospital stay (LHS) were compared. Oncologic outcomes assessed were number of lymph nodes harvested and lengths of proximal and distal resection margins. RESULTS: Twenty-four studies (2 RCTs and 22 NRCTs [5 prospective plus 17 retrospective]) with a total of 3318 patients were included. Of these, 1466 (44.18 %) patients underwent RACS and 1852 (55.82 %) underwent LACS. Conversion rates, EBL and LHS were significantly lower, while the operation times and total costs were similar between RACS and LACS. Complication rates and oncological accuracy of resection showed no significant difference. CONCLUSION: Based on this meta-analysis, RACS appears to be a promising surgical approach with its safety and efficacy comparable to that of LACS in patients undergoing colorectal surgery. Further studies are required to evaluate the long-term cost efficiency as well as the functional and oncologic outcomes of RACS. PMID- 27402098 TI - Human exposure assessment of silver and copper migrating from an antimicrobial nanocoated packaging material into an acidic food simulant. AB - To examine the human exposure to a novel silver and copper nanoparticle (AgNP and CuNP)/polystyrene-polyethylene oxide block copolymer (PS-b-PEO) food packaging coating, the migration of Ag and Cu into 3% acetic acid (3% HAc) food simulant was assessed at 60 degrees C for 10 days. Significantly lower migration was observed for Ag (0.46 mg/kg food) compared to Cu (0.82 mg/kg food) measured by inductively coupled plasma - atomic emission spectrometry (ICP-AES). In addition, no distinct population of AgNPs or CuNPs were observed in 3% HAc by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The predicted human exposure to Ag and Cu was used to calculate a margin of exposure (MOE) for ionic species of Ag and Cu, which indicated the safe use of the food packaging in a hypothetical scenario (e.g. as fruit juice packaging). While migration exceeded regulatory limits, the calculated MOE suggests current migration limits may be conservative for specific nano-packaging applications. PMID- 27402099 TI - Effect of formulation variables on oral grittiness and preferences of multiparticulate formulations in adult volunteers. AB - Multiparticulate formulations are composed of multiple solid dosage units which can be administered directly to the mouth or sprinkled on food. Oral grittiness (i.e. rough mouthfeel) may arise from the presence of particles in the mouth, limiting palatability. In this work, multiparticulate formulations were prepared by dispersion of spherical granules into orange flavoured vehicles thickened with hypromellose (HPMC) at different viscosities in order to assess oral perception of grittiness by a panel of thirty adults through direct scaling on a 100mm visual analogue scale. The effect of formulation factors such as particle size (90, 127, 263MUm), amount of particles per 10ml (0.25, 0.50, 1.00g) and viscosity of the vehicle (0.08, 0.43, 2.80Pas) were investigated. Grittiness was increasingly perceived with increasing amount and size of particles. Increasing viscosity of the administration media had a masking effect on the perception of particles. Less gritty samples were generally regarded as 'more pleasant' by the participants of the study. However, samples dispersed in thickened vehicles seemed to be less preferred despite being less gritty; which could be ascribed to an unpleasant mouthfeel of the vehicle. In the design of multiparticulate formulations acceptable for a targeted patient group all these formulation factors will need to be considered and optimised. PMID- 27402101 TI - Comparing primate crania: The importance of fossils. AB - OBJECTIVES: Extant primate crania represent a small subset of primate crania that have existed. The main objective here is to examine how the inclusion of fossil crania changes our understanding of primate cranial diversity relative to analyses of extant primates. We hypothesize that fossil taxa will change the major axes of cranial shape, occupy new areas of morphospace, change the relative diversity of major primate clades, and fill in notable gaps separating major primate taxa/clades. MATERIALS AND METHODS: Eighteen 3D landmarks were collected on 157 extant and fossil crania representing 90 genera. Data were subjected to a Generalized Procrustes Analysis then principal components analysis. Relative diversity between clades was assessed using an F-statistic. RESULTS: Fossil taxa do not significantly alter major axes of cranial shape, but they do occupy unique areas of morphospace, change the relative diversity between clades, and fill in notable gaps in primate cranial evolution. Strepsirrhines remain significantly less diverse than anthropoids. Fossil hominins fill the gap in cranial morphospace between extant great apes and modern humans. DISCUSSION: The morphospace outlined by living primates largely includes that occupied by fossil taxa, suggesting that the cranial diversity of living primates generally encompasses the total diversity that has evolved in this Order. The evolution of the anthropoid cranium was a significant event allowing anthropoids to achieve significantly greater cranial diversity compared to strepsirrhines. Fossil taxa fill in notable gaps within and between clades, highlighting their transitional nature and eliminating the appearance of large morphological distances between extant taxa, particularly in the case of extant hominids. PMID- 27402100 TI - Critical material attributes (CMAs) of strip films loaded with poorly water soluble drug nanoparticles: I. Impact of plasticizer on film properties and dissolution. AB - Recent studies have demonstrated polymer films to be a promising platform for delivery of poorly water-soluble drug particles. However, the impact of critical material attributes, for example plasticizer, on the properties of and drug release from such films has yet to be investigated. In response, this study focuses on the impact of plasticizer and plasticizer concentration on properties and dissolution rate of polymer films loaded with poorly water-soluble drug nanoparticles. Glycerin, triacetin, and polyethylene glycol were selected as film plasticizers. Griseofulvin was used as a model Biopharmaceutics Classification System class II drug and hydroxypropyl methylcellulose was used as a film-forming polymer. Griseofulvin nanoparticles were prepared via wet stirred media milling in aqueous suspension. A depression in film glass transition temperature was observed with increasing plasticizer concentration, along with a decrease in film tensile strength and an increase in film elongation, as is typical of plasticizers. However, the type and amount of plasticizer necessary to produce strong yet flexible films had no significant impact on the dissolution rate of the films, suggesting that film mechanical properties can be effectively manipulated with minimal impact on drug release. Griseofulvin nanoparticles were successfully recovered upon redispersion in water regardless of plasticizer or content, even after up to 6months' storage at 40 degrees C and 75% relative humidity, which contributed to similar consistency in dissolution rate after 6months' storage for all films. Good content uniformity (<4% R.S.D. for very small film sample size) was also maintained across all film formulations. PMID- 27402102 TI - A survey on fertility management in young women of reproductive age treated with chemotherapy. AB - BACKGROUND: Treatment-related infertility is an important issue for cancer survivors of reproductive age. We aimed to determine the understanding and management of fertility issues in cancer survivors by health care providers. METHODS: We studied 112 patients aged 15-40 years who underwent chemotherapy in Tokushima University Hospital. The gynecologists and oncologists who treated these patients were surveyed regarding their concerns about infertility issues in young cancer survivors. RESULTS: Of the 112 women studied, 57 had iatrogenic amenorrhea. Five were referred to reproductive specialists before or during treatment. Three patients with breast cancer were referred after treatment; they could not undergo fertility treatment due to ovarian failure after chemotherapy. Forty-five medical doctors answered the survey: 21 gynecologists (including 9 fertility specialists), 13 oncologists, and 11 surgeons. Of the oncologists and surgeons, 37.5 % (9/24) referred their patients to fertility experts. They listed certain issues regarding the patients: (1) anxiety that the intervention will alter the prognosis by delaying cancer treatment, and (2) a lack of communication between the oncologist and the fertility specialist. Almost all physicians agreed that fertility counseling was needed before chemotherapy. CONCLUSION: This report showed the importance of oncofertility counseling and cooperation between oncologists and fertility specialists. Fertility in cancer survivors depends on type of cancer treatment applied, chemotherapy regimen, and age at treatment. Our institute is now equipped for oncofertility counseling and refers patients for fertility preservation prior to cancer treatment. PMID- 27402103 TI - Improvement of renal function by changing the bone-modifying agent from zoledronic acid to denosumab. AB - BACKGROUND: In order to help in selecting the optimum bone-modifying agent (BMA; zoledronic acid or denosumab), we investigated the impact of the BMA on the renal function of patients with bone metastases. MATERIALS AND METHODS: The present study consisted of 118 patients who were treated with denosumab for bone metastases secondary to prostate cancer, renal cell cancer, and urothelial cancer at our hospital between 2012 and 2015. The clinical course of the renal function of these patients, treated with zoledronic acid or denosumab, was retrospectively evaluated. RESULTS: Of the 118 patients who were treated with denosumab during the study period, 57 (48 %) had previously been administered zoledronic acid and 61 (52 %) had received denosumab as the first-line BMA. The reasons for changing from zoledronic acid to denosumab were increased creatinine serum level (26 patients, 46 %), patient preference (16 patients, 28 %), difficulty with venous infusion (10 patients, 17 %), and other reasons (5 patients, 9 %). The median level of creatinine clearance in the patients who changed from zoledronic acid to denosumab due to increased serum creatinine level was 59.9 ml/min before administration of zoledronic acid, 40.9 ml/min at the beginning of denosumab treatment, 47.5 ml/min at 3 months after administration of denosumab, and 52.0 ml/min at the last follow-up. There were significant differences. CONCLUSIONS: For the first time, we demonstrated that the renal function of some patients, which had deteriorated following zoledronic acid administration, successfully improved after changing to denosumab. PMID- 27402104 TI - The impact of body mass index on oncological outcomes in colorectal cancer patients with curative intent. AB - BACKGROUND: Excess body weight is associated with a risk of several malignancies, including colon cancer. However, the oncological significance of evaluating body mass index (BMI) preoperatively in colorectal cancer (CRC) patients undergoing curative surgery has not been fully evaluated. METHODS: Clinicopathological findings including BMI and laboratory data [carcinoembryonic antigen (CEA) and neutrophil/lymphocyte ratio (NLR)] from 358 curative CRC patients (open surgery group: n = 157; laparoscopic surgery group: n = 201) were assessed as indicators of survival outcome. BMI <20 was defined as underweight in both groups. RESULTS: Not all categories of pathological findings were associated with BMI in both groups. Patients with BMI <20 showed significant poorer overall survival (OS) in the open surgery group. In addition, patients with BMI <20 in the laparoscopic surgery group were also significantly worse in OS and disease-free survival (DFS). Furthermore, multivariate analysis demonstrated that BMI was validated as independent predictors for OS and DFS in both groups. BMI had a significant negative correlation with NLR, which reflects host immune response in both groups. CONCLUSIONS: Lower BMI is a promising predictor of recurrence and prognosis in curative CRC patients. PMID- 27402105 TI - Small bowel adenocarcinoma of the jejunum: a case report and literature review. AB - BACKGROUND: In practice, small bowel cancer is a rare entity. The most common histologic subtype is adenocarcinoma. Adenocarcinoma of the small bowel (SBA) is challenging to diagnose, often presents at a late stage and has a poor prognosis. The treatment of early-stage SBA is surgical resection. No standard protocol has been established for unresectable or metastatic disease. CASE PRESENTATION: We report here on a 26-year-old man with SBA in the jejunum, lacking specific symptoms and with a delay of 6 months in diagnosis. The diagnosis was finally achieved with a combination of balloon-assisted enteroscopy, computed tomography scans, positron emission computed tomography scans and the values of carcino embryonic antigen and carbohydrate antigen 19-9. The patient underwent segmental intestine with lymph node resection, followed by eight cycles of FOLFOX palliative chemotherapy with good tolerance. As of the 11-month postoperative follow-up, there has been no evidence of recurrent disease. CONCLUSIONS: This case is reported to arouse a clinical suspicion of SBA in patients with abdominal pain of unknown cause. We also provided evidence in this case of a response to palliative chemotherapy with FOLFOX. Because the incidence of SBA is very low, there is a need for further studies to evaluate the possible application of newer investigative agents and strategies to obtain a better outcome within the framework of international collaborations. PMID- 27402106 TI - Erectile Dysfunction in Systemic Sclerosis. AB - Erectile dysfunction (ED) is a major issue in systemic sclerosis (SSc) as it is observed in around 80 to 90 % of men with this connective tissue disease. ED greatly impacts the quality of life and should be actively addressed as a common complication. Whereas ED in the general population is usually associated with risk factors for atherosclerosis as well as cardiovascular disease, the main aetiology of ED in SSc is microangiopathic. In SSc, the blood flow is reduced in the small penile arteries due to corporal fibrosis and myointimal proliferation. There are no data on the prevention of ED in SSc. On-demand phosphodiesterase-5 inhibitors have little effect in improving erectile function, but daily or alternate day regimens of long-acting phosphodiesterase-5 inhibitors provide a measurable, although often limited, benefit. When intracavernous prostaglandin E1 injections are also ineffective, the implantation of a penile prosthesis should be considered as an option. PMID- 27402107 TI - Pharmacoeconomics of Biosimilars: What Is There to Gain from Them? AB - Despite representing a breakthrough in the treatment of immune-mediated rheumatic diseases, the direct costs of biotechnological therapies represent a burden to healthcare budgets worldwide. Furthermore, several studies demonstrated that socioeconomically constrained countries have poorer access to these therapies and this has consequences on the optimal management of rheumatic patients. Experience with small peptide biosimilars like filgrastim and epoetin confirmed significant cost savings but revealed variable market uptake. In this report, we summarize the available budget impact models and discuss possible determinants of the pharmacoeconomic performance of antirheumatic biosimilar drugs. PMID- 27402108 TI - Preventive Treatments for Rheumatoid Arthritis: Issues Regarding Patient Preferences. AB - The detection of biomarkers in the preclinical phase of rheumatoid arthritis (RA) and recent therapeutic advances suggest that it may be possible to identify and treat persons at high risk and to prevent the development of RA. Several trials are ongoing to test the efficacy of a therapeutic intervention in primary prevention. This paper reviews potential populations that might be considered for preventative medication. Further, we review the medications that are being explored to treat individuals considered at high risk of developing RA. Finally, in a group of asymptomatic individuals at high risk of developing RA, we assessed which factors mattered most when considering a preventive therapeutic intervention and what type of preventive treatment would be most acceptable to them. Understanding subjects' perceptions of risks and benefits and willingness to undergo preventive therapy will be important in designing and implementing screening and preventive strategies. PMID- 27402110 TI - Economic Theory and Self-Reported Measures of Presenteeism in Musculoskeletal Disease. AB - This study had two objectives: to describe the historical development of self reported presenteeism instruments that can be used to identify and measure presenteeism as a result of musculoskeletal disease (MSD) and to identify if, and how many of these, presenteeism instruments are underpinned by economic theory. Systematic search methods were applied to identify self-report instruments used to quantify presenteeism caused by MSD. A total of 24 self-reported presenteeism instruments were identified; 24 were designed for use in general health, and 1 was specifically designed for use in rheumatoid arthritis. One generic self reported presenteeism instrument was explicitly reported to be underpinned by economic theory. Overtime, self-reported presenteeism instruments have become more differentiated and complex by incorporating many different contextual factors that may impact levels of presenteeism. Researchers are encouraged to further develop presenteeism instruments that are underpinned by relevant economic theory and informed by robust empirical research. PMID- 27402109 TI - Histone Deacetylases in Cartilage Homeostasis and Osteoarthritis. AB - The involvement of the epigenome in complex diseases is becoming increasingly clear and more feasible to study due to new genomic and computational technologies. Moreover, therapies altering the activities of proteins that modify and interpret the epigenome are available to treat cancers and neurological disorders. Many additional uses have been proposed for these drugs based on promising preclinical results, including in arthritis models. Understanding the effects of epigenomic drugs on the skeleton is of interest because of its importance in maintaining overall health and fitness. In this review, we summarize ongoing advancements in how one class of epigenetic modifiers, histone deacetylases (Hdacs), controls normal cartilage development and homeostasis, as well as recent work aimed at understanding the alterations in the expression and activities of these enzymes in osteoarthritis (OA). We also review recent studies utilizing Hdac inhibitors and discuss the potential therapeutic benefits and limitations of these drugs for preventing cartilage destruction in OA. PMID- 27402111 TI - Neuromyelitis Optica (Devic's Syndrome): an Appraisal. AB - Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD), previously known as Devic's syndrome, are a group of inflammatory disorders of the central nervous system (CNS) characterized by severe, immune-mediated demyelination and axonal damage, predominantly targeting optic nerves and the spinal cord typically associated with a disease-specific serum NMO-IgG antibody that selectively binds aquaporin-4 (AQP4). The classic and best-defined features of NMOSD include acute attacks of bilateral or rapidly sequential optic neuritis (leading to visual loss) or transverse myelitis (often causing limb weakness and bladder dysfunction) or both with a typically relapsing course. The diagnosis of NMO/NMOSD requires a consistent history and examination with typical clinical presentations, findings on spinal cord neuroimaging with MRI, cerebrospinal fluid analysis along with determination of AQP4-IgG serum autoantibody status, and exclusion of other disorders. Two major advances in this field has been the development of diagnostic criteria and treatment recommendations. Consensus diagnostic criteria have been established and were recently revised and published in 2015, enhancing the ability to make a diagnosis and appropriately evaluate these disorders. Expert recommendations and uncontrolled trials form the basis of treatment guidelines. All patients with suspected NMOSD should be treated for acute attacks as soon as possible with high-dose intravenous methylprednisolone 1 gram daily for three to five consecutive days and in some cases, plasma exchange should be used. It is recommended that every patient with NMOSD be started on an immunosuppressive agent, such as, azathioprine, methotrexate, or mycophenolate and in some cases, rituximab, soon after the acute attack and usually be treated for about 5 years after the attack. These advances have helped improve the prognosis and outcome in these disorders. PMID- 27402112 TI - Juvenile Spondyloarthropathies. AB - Juvenile spondyloarthropathies represent a clinical entity separate from the adult disease. Initial clinical signs of juvenile spondyloarthropathies often include lower extremity arthritis and enthesopathy, without axial involvement at the disease onset. Asymmetrical oligoarthritis of lower extremities is typically seen in this type of arthritis. Enthesopathy, which is the hallmark of the disease, is most commonly seen in the Achilles tendon, being manifested by heel pain. Anterior uveitis and HLA-B27 positivity are seen in a proportion of cases. Sacroiliitis is generally asymptomatic in the pediatric population. Ineffective treatment of childhood disease results in disease progression to typical adult form of ankylosing spondylitis. Therefore, early diagnosis and classification remains one of the most relevant questions in pediatric rheumatology. It should be kept in mind that the disease could be misdiagnosed as FMF or Behcet's syndrome in countries with a high incidence of those conditions. This review revises available classification criteria, clinical manifestations and therapeutic options for patients with juvenile spondyloarthropathies. PMID- 27402114 TI - Total dosage of gardenia fruit used by patients with mesenteric phlebosclerosis. AB - BACKGROUND: Mesenteric phlebosclerosis (MP) is a disease characterized by fibrotic change or calcification of the mesenteric vein. Recently, there has been an increase in case reports of MP related to herbal medicine usage. Long-term intake of gardenia fruit (GF) is suspected as a possible cause. However, many GF users do not develop this disease and the association between GF and MP remains unclear. In this study, we investigated for the first time the dosage of GF used by patients with and without MP. METHODS: We used a medical chart review study design to assess the association between GF and MP. We reviewed patients with a history of intake of herbal medicines containing GF. Among these patients, we selected patients who were examined by colonoscopy and abdominal plain computed tomography (CT). We investigated the findings of colonoscopy, CT scan and histological examination. We assessed the total dosages of GF alongside the duration of ambulatory visit, the administration period of herbal medicine containing GF and pre-existing disease in order to compare MP cases and non-MP patients. RESULTS: Ten MP cases and 42 non-MP patients were analyzed. We summarized clinical findings of MP cases. All MP cases used more GF than non-MP patients and were administered more than approximately 5,000 grams of GF in cumulative dosage. CONCLUSIONS: This study indicated that excessive intake of GF contributes to and/or accelerates the development of MP suggesting that long-term usage of GF in excessive amounts increases the risk of MP. PMID- 27402113 TI - The Role of MicroRNAs and Their Targets in Osteoarthritis. AB - Micro ribonucleic acid (microRNA) regulation and expression has become an emerging field in determining the mechanisms regulating a variety of inflammation mediated diseases. Several studies have focused on specific microRNAs that are differentially expressed in cases of osteoarthritis. Furthermore, several targets of these miRNAs important in disease progression have also been identified. In this review, we focus on microRNA biogenesis, regulation, detection, and quantification with an emphasis on cellular localization and how these concepts may be linked to disease processes such as osteoarthritis. Next, we review the relationships of specific microRNAs to certain features and risk factors associated with osteoarthritis such as inflammation, obesity, autophagy, and cartilage homeostasis. We also identify certain microRNAs that are differentially expressed in osteoarthritis but have unidentified targets and functions in the disease state. Lastly, we identify the potential use of microRNAs for therapeutic purposes and also mention certain remedies that regulate microRNA expression. PMID- 27402115 TI - Prognostic significance of annexin A2 and annexin A4 expression in patients with cervical cancer. AB - BACKGROUND: The annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer. METHODS: ANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases and compared the data with clinicopathological variables, including the survival of cervical cancer patients. RESULTS: ANXA2 expression was lower in cancer tissue (p = 0.002), whereas ANXA4 staining increased significantly in cancer tissues (p < 0.001). ANXA2 expression was more prominent in squamous cell carcinoma (p < 0.001), whereas ANXA4 was more highly expressed in adeno/adenosquamous carcinoma (p < 0.001). ANXA2 overexpression was positively correlated with advanced cancer phenotypes, whereas ANXA4 expression was associated with resistance to radiation with or without chemotherapy (p = 0.029). Notably, high ANXA2 and ANXA4 expression was significantly associated with shorter disease-free survival (p = 0.004 and p = 0.033, respectively). Multivariate analysis indicated that ANXA2+ (HR = 2.72, p = 0.003) and ANXA2+/ANXA4+ (HR = 2.69, p = 0.039) are independent prognostic factors of disease-free survival in cervical cancer. Furthermore, a random survival forest model using combined ANXA2, ANXA4, and clinical variables resulted in improved predictive power (mean C-index, 0.76) compared to that of clinical-variable-only models (mean C-index, 0.70) (p = 0.006). CONCLUSIONS: These findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis. PMID- 27402116 TI - A review of the role of surgery for small cell lung cancer and the potential prognostic value of enumeration of circulating tumor cells. AB - Small cell lung cancer (SCLC) is disseminated in the majority of patients at first presentation and, thus, treated with chemoradiotherapy. Despite initial high response rates, chemoresistance appears rapidly and results in a dismal prognosis. However, patients with limited cancer may exhibit better disease control upon surgical treatment. Correct staging is highly critical in the selection of those patients which are likely to benefit from surgery. Studies of the inclusion of surgery in the multimodal treatment of SCLC vary widely in number of patients, selection, treatment and follow-up. Nevertheless surgical therapy for confined SCLCs achieves favorable long-term survival compared to chemoradiotherapy, depending on a precise assessment of the degree of tumor dissemination. Recently, extremely high counts of circulating tumor cells (CTCs) were reported in patients with SCLC compared to other malignancies. In several studies the number of CTCs was found to constitute a prognostic parameter and a marker of response to therapy. Therefore, the assessment of CTCs as so-called "Liquid Biopsy" seems to constitute a more precise method to detect tumor dissemination earlier when compared to clinical staging. In conclusion, in the era of precision oncology enumeration and identification of CTCs of SCLC patients have the potential to help in the selection of patients most suitable for tumor surgery. PMID- 27402117 TI - Assessment of the Risks of Mixtures of Major Use Veterinary Antibiotics in European Surface Waters. AB - Effects of single veterinary antibiotics on a range of aquatic organisms have been explored in many studies. In reality, surface waters will be exposed to mixtures of these substances. In this study, we present an approach for establishing risks of antibiotic mixtures to surface waters and illustrate this by assessing risks of mixtures of three major use antibiotics (trimethoprim, tylosin, and lincomycin) to algal and cyanobacterial species in European surface waters. Ecotoxicity tests were initially performed to assess the combined effects of the antibiotics to the cyanobacteria Anabaena flos-aquae. The results were used to evaluate two mixture prediction models: concentration addition (CA) and independent action (IA). The CA model performed best at predicting the toxicity of the mixture with the experimental 96 h EC50 for the antibiotic mixture being 0.248 MUmol/L compared to the CA predicted EC50 of 0.21 MUmol/L. The CA model was therefore used alongside predictions of exposure for different European scenarios and estimations of hazards obtained from species sensitivity distributions to estimate risks of mixtures of the three antibiotics. Risk quotients for the different scenarios ranged from 0.066 to 385 indicating that the combination of three substances could be causing adverse impacts on algal communities in European surface waters. This could have important implications for primary production and nutrient cycling. Tylosin contributed most to the risk followed by lincomycin and trimethoprim. While we have explored only three antibiotics, the combined experimental and modeling approach could readily be applied to the wider range of antibiotics that are in use. PMID- 27402118 TI - Chain length, temperature and solvent effects on the structural properties of alpha-aminoisobutyric acid homooligopeptides. AB - Non-coded alpha-amino acids, originally exploited by nature, have been successfully reproduced by recent synthetic strategies to confer special structural and functional properties to small peptides. The most known and well studied atypical residue is alpha-aminoisobutyric acid (Aib), which is contained in a fairly large number of peptides with known antibiotic effects. Here, we report on a molecular dynamics (MD) study of a series of homooligopeptides based on alpha-aminoisobutyric acid (Aib) with increasing length (Ac-(Aib)n-NMe, n = 5, 6, 7 and 10) and at various temperatures, employing a recent extension of the AMBER force field tailored for the Aib residue. Solvent effects have been analyzed by comparative MD simulations of a heptapeptide in water and dimethylsulfoxide at different temperatures. Our results show that the preference for the 310- and/or alpha-helix structures, which typically characterize Aib based peptides, is finely tuned by several factors including the chain length, temperature and solvent nature. While the transitions between intra-molecular i > i + 3 and i -> i + 4 hydrogen bonds characterizing 310 and alpha-helices, respectively, are rather fast in small peptides (in the picosecond timescale), our analysis shows that the above physical and chemical factors modulate the relative equilibrium populations of the two helical structures. The obtained results nicely agree with available experimental data and support the use of the new force field for modeling Aib containing peptides. PMID- 27402119 TI - Barriers to continuity in the pathway toward occupational engagement among ethnic minorities with mental illness. AB - Ethnic minorities have particular needs and difficulties in terms of support for meaningful occupations, lack of access to and use of occupation-based rehabilitation services. They are not established in the labour market and are seldom in paid employment. This study aimed to investigate how mentally ill ethnic minority clients experience, feel and think about participation in occupation-based rehabilitation, and potential barriers they might encounter. Nine participants experiencing mental illness and receiving occupation-based rehabilitation were interviewed. Grounded theory methods were used in order to collect and analyze data. One core category, "barriers for a continuous path towards enriched and meaningful occupation" described the participants' experiences of a variety of barriers related to personal, occupational and system factors that hindered participation in occupation-based rehabilitation and influenced their need for occupational development and growth. The core category was composed of; personal-related barriers, occupational-related barriers, and system-related barriers as well as six related sub-categories. These barriers interacted continually across time and space in ways that increased the participants' sense of occupational deprivation and alienation. The findings also suggested that the issues of paid employment for ethnic minorities with mental illness should feature on the agenda of local, regional and state politicians and professionals involved in occupational rehabilitation. PMID- 27402120 TI - The functional role for condensin in the regulation of chromosomal organization during the cell cycle. AB - In all organisms, the control of cell cycle progression is a fundamental process that is essential for cell growth, development, and survival. Through each cell cycle phase, the regulation of chromatin organization is essential for natural cell proliferation and maintaining cellular homeostasis. During mitosis, the chromatin morphology is dramatically changed to have a "thread-like" shape and the condensed chromosomes are segregated equally into two daughter cells. Disruption of the mitotic chromosome architecture physically impedes chromosomal behaviors, such as chromosome alignment and chromosome segregation; therefore, the proper mitotic chromosome structure is required to maintain chromosomal stability. Accumulating evidence has demonstrated that mitotic chromosome condensation is induced by condensin complexes. Moreover, recent studies have shown that condensin also modulates interphase chromatin and regulates gene expression. This review mainly focuses on the molecular mechanisms that condensin uses to exert its functions during the cell cycle progression. Moreover, we discuss the condensin-mediated chromosomal organization in cancer cells. PMID- 27402122 TI - Gray Areas in Language-Concordant Healthcare: a Graduating Medical Student's Reflection on the Experience and Research on Language and Cultural Competence. PMID- 27402123 TI - [Not Available]. PMID- 27402124 TI - [Not Available]. PMID- 27402125 TI - [Possible side effects from HPV vaccination in Denmark]. AB - HPV vaccination offers protection against ~70% of cervical cancers, however, serious concerns have been raised about the possible side effects from HPV vaccination. Studies have found no increased risk of neurologic disease, autoimmune disorder, thromboembolic disease, postural orthostatic tachycardia syndrome, or complex regional pain syndrome in HPV-vaccinated persons compared to unvaccinated persons. Affected individuals should undergo a proper clinical examination to ensure a correct diagnosis and treatment, because symptoms might arise due to a somatic, psychiatric or functional disorder. PMID- 27402126 TI - [Herpes zoster-neuritis med svaer parese af hojre skulder]. PMID- 27402121 TI - The CB2 receptor and its role as a regulator of inflammation. AB - The CB2 receptor is the peripheral receptor for cannabinoids. It is mainly expressed in immune tissues, highlighting the possibility that the endocannabinoid system has an immunomodulatory role. In this respect, the CB2 receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases. In this regard, numerous studies have reported that mice lacking the CB2 receptor have an exacerbated inflammatory phenotype. This suggests that therapeutic strategies aiming at modulating CB2 signaling could be promising for the treatment of various inflammatory conditions. Herein, we review the pharmacology of the CB2 receptor, its expression pattern, and the signaling pathways induced by its activation. We next examine the regulation of immune cell functions by the CB2 receptor and the evidence obtained from primary human cells, immortalized cell lines, and animal models of inflammation. Finally, we discuss the possible therapies targeting the CB2 receptor and the questions that remain to be addressed to determine whether this receptor could be a potential target to treat inflammatory disease. PMID- 27402127 TI - [Diagnosis and treatment of rare causes of ischaemic stroke]. AB - Rare causes of ischaemic stroke comprise a plethora of diagnoses of cardioembolic, inflammatory and genetic origin. The differential diagnosis is challenging but important because these disorders (e.g. monogenetic disorders such as COL4A1 mutations) often affect young individuals, they typically require sophisticated diagnostics (e.g. fluorescence angiography in Susac's syndrome) and they are increasingly treatable (e.g. enzyme replacement for Fabry's disease). This review discusses practical considerations and recent diagnostic and therapeutic advances in uncommon causes of ischaemic stroke. PMID- 27402128 TI - [Malignant adnexal carcinomas of the skin]. AB - Malignant adnexal carcinomas of the skin are rare but associated with high propensity for local recurrence, and for some of the distinct subgroups they are known to metastasize regionally or distant. Biopsy is necessary for correct diagnosis, as the lesions cannot be separated from other tumour types entirely on their clinical appearance. The histologic diagnosis is troublesome, and the lesions are often mistaken for their benign counterpart, basal cell carcinoma or squamous cell carcinoma. The lesions are treated with surgery. Radiotherapy and chemotherapy may play a role in treatment, although the evidence is limited. PMID- 27402129 TI - [Pharmacological therapy of asthma during pregnancy]. AB - Asthma is one of the most frequent chronic diseases which complicate pregnancy. Well-controlled asthma during pregnancy reduces the risk of for exacerbations and, consequently, the risk of adverse pregnancy outcome. Pharmacological therapy for pregnant women with asthma is a challenge, not least due to suboptimal adherence with controller therapy and pregnant women's concerns about harmful effects of medication on the fetus. This review provides an update on the safety of asthma medication during pregnancy, based on recent clinical studies and international guidelines. PMID- 27402130 TI - Epidemiology of Pulmonary Hypertension in Left Heart Disease. AB - Pulmonary hypertension (PH) in the setting of left side heart disease is associated with adverse outcomes. The exact prevalence of PH in the different pathologies that affect the left ventricle, however, is difficult to access with the current literature. The lack of a standard definition of PH in older studies, the different modalities to assess pulmonary artery pressures and the varying disease severity, all account for the great variability in the reported prevalence of PH. PH can accompany heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) as well as mitral and aortic valve disease; in any of these instances it is important to recognize whether the elevation of pulmonary pressures is driven by elevated left ventricular pressures only (isolated post-capillary PH) or if there is an accompanying remodeling component in the pulmonary arterioles (combined post-capillary and pre-capillary PH). The objective of this review is to describe the definitions, prevalence and the risk factors associated with the development of PH in the setting of HFrEF, HFpEF and valvular heart disease. PMID- 27402131 TI - Expanding the Donor Pool With Normothermic Ex Vivo Liver Perfusion: The Future Is Now. PMID- 27402132 TI - Evaluation of Oxidative Metabolism in Leukocytes during Phagocytosis of Escherichia coli Carrying Genetic Constructs soxS::lux or katG::lux. AB - We studied ROS generation by human peripheral blood monocytes and granulocytes during phagocytosis of Escherichia coli soxS::lux or katG::lux responding by luminescence (bioluminescence) to the development of oxidative stress. Initially high sensitivity of the bioluminescent reaction of E. coli katG::lux strain to the effects of model ROS (KO2 and H2O2) and pronounced induction of luminescence upon contact with granulocytes, whereas E. coli soxS::lux demonstrated less pronounced reaction to chemical oxidants and bioluminescence was observed primarily upon contact with monocytes. A correlation was found between quantitative characteristics of E. coli katG::lux bioluminescence and luminol dependent chemiluminescence of leukocytes in some patients, but no dependence of this kind was noted for E. coli soxS::lux. The results can provide experimental substantiation of a new approach for evaluation of ROS production by leukocytes during phagocytosis and choosing the optimal object for these studies. PMID- 27402133 TI - Immune response in human chromoblastomycosis and eumycetoma - focusing on human interleukin-17A, interferon-gamma, tumour necrosis factor-alpha, interleukin-1 beta and human beta-defensin-2. AB - Knowledge regarding host immune response to chromoblastomycosis and eumycetoma is limited, particularly concerning cytokines and antimicrobial peptides production. This was a retrospective study of 12 paraffin-embedded tissue samples from patients diagnosed with chromoblastomycosis or eumycetoma from histological findings and tissue culture. DNA extraction and polymerase chain reaction (PCR) from tissues were done to evaluate human interleukin-17A (IL-17A), interferon gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and human beta-defensin-2 (HBD-2) expressions. Human beta-actin primer was used for confirming DNA detection, and DNA extracted from psoriasis lesional skin samples was used as positive controls. The twelve paraffin-embedded sections used in this study consisted of five chromoblastomycosis and seven eumycetoma tissues. All PCR reactions showed beta-actin band at 51 bp in all clinical specimens, confirming adequate DNA levels in each reaction. As positive control, the psoriasis skin samples revealed bands for IL-17A at 174 bp, IFN-gamma at 273 bp, TNF-alpha at 360 bp, IL-1beta at 276 bp and HBD-2 at 255 bp. For the chromoblastomycosis and eumycetoma tissues, PCR analyses showed IL-17A band at 174 bp in two eumycetoma tissues and HBD-2 band at 255 bp in a chromoblastomycosis tissue. This study demonstrated IL-17A expression in human eumycetoma and HBD-2 expression in human chromoblastomycosis for the first time. However, their role in immune response remains to be elucidated. PMID- 27402135 TI - Can the British Heart Foundation PocketCPR application improve the performance of chest compressions during bystander resuscitation: A randomised crossover manikin study. AB - This study aims to determine whether the British Heart Foundation PocketCPR training application can improve the depth and rate of chest compression and therefore be confidently recommended for bystander use. A total of 118 candidates were recruited into a randomised crossover manikin trial. Each candidate performed cardiopulmonary resuscitation for 2 min without instruction or performed chest compressions using the PocketCPR application. Candidates then performed a further 2 min of cardiopulmonary resuscitation within the opposite arm. The number of chest compressions performed improved when PocketCPR was used compared to chest compressions when it was not (44.28% vs 40.57%, p < 0.001). The number of chest compressions performed to the required depth was higher in the PocketCPR group (90.86 vs 66.26). The British Heart Foundation PocketCPR application improved the percentage of chest compressions that were performed to the required depth. Despite this, more work is required in order to develop a feedback device that can improve bystander cardiopulmonary resuscitation without creating delay. PMID- 27402134 TI - Diagnosis of myocardial infarction and ischemia in the setting of bundle branch block and cardiac pacing. AB - The diagnosis of myocardial infarction (MI) in the presence of left bundle branch block (LBBB) or during ventricular pacing (VP) is challenging because of inherent changes in the sequence of ventricular depolarization and repolarization associated with both conditions. Although LBBB and right ventricular (RV) pacing may both produce abnormalities in the ECG, it is often possible to diagnose an acute MI (AMI) or an old MI based on selected morphologic changes. Primary ST segment changes scoring 3 points or greater according to the Sgarbossa criteria are highly predictive of an AMI in patients with LBBB or RV pacing. The modified Sgarbossa criteria are useful for the diagnosis of AMI in patients with LBBB; however, these criteria have not yet been studied in the setting of RV pacing. Although changes of the QRS complex are not particularly sensitive for the diagnosis of an old MI in the setting of LBBB or RV pacing, the qR complex and Cabrera sign are highly specific for the presence of an old infarct. Diagnosing AMI in the setting of biventricular (BiV) pacing is challenging. To date there is minimal evidence suggesting that the traditional electrocardiographic criteria for diagnosis of AMI in bundle branch block may be applicable to patients with BiV pacing and positive QRS complexes on their ECG in lead V1. This report is a careful review of the electrocardiographic criteria facilitating the diagnosis of acute and remote MI in patients with LBBB and/or VP. PMID- 27402136 TI - Preface to the Special Issue for the XXVI International Complement Workshop. PMID- 27402137 TI - Personal Journal Keeping and Linguistic Complexity Predict Late-Life Dementia Risk: The Cache County Journal Pilot Study. AB - Objectives: We determined the feasibility of accessing personal journals and correlating markers of linguistic complexity with all-cause dementia and Alzheimer's disease (AD). Method: A stratified random sample of 215 older adults reported on lifetime journal writing habits. From 66 of these participants (49% of those with journals), digital photographs of journal text were transcribed then subjected to the Linguistic Inquiry Word Count program to measure linguistic complexity markers: Words per Sentence, Percentage of 6+ Letter Words, Cognitive Mechanics, Percentage of Unique Words, and Percentage of Words that are Numerals. AD diagnosis was made via in-depth clinical protocol. Results: In the larger sample, ever being a journal writer significantly predicted a 53% reduction in all-cause dementia risk. In the subsample with transcribed writings, Percentage of 6+ Letter Words predicted AD and all-cause dementia risk, with all logistic regression models controlling for age, education, gender, and Latter-Day Saints affiliation. Discussion: These data suggest the potential viability of adulthood language use as a predictive tool for late-life AD risk, both in the linguistic features and the practice of journal writing itself. PMID- 27402138 TI - Online patient websites for electronic health record access among vulnerable populations: portals to nowhere? AB - Objective: With the rapid rise in the adoption of patient portals, many patients are gaining access to their personal health information online for the first time. The objective of this study was to examine specific usability barriers to patient portal engagement among a diverse group of patients and caregivers. Materials and Methods: We conducted interviews using performance testing and think-aloud methods with 23 patients and 2 caregivers as they first attempted to use features of a newly launched patient portal. Results: In navigating the portal, participants experienced basic computer barriers (eg, difficulty using a mouse), routine computer barriers (eg, mistyping, navigation issues), reading/writing barriers, and medical content barriers. Compared to participants with adequate health literacy, participants with limited health literacy required 2 additional minutes to complete each task and were more likely to experience each type of navigational barrier. They also experienced more inaccuracies in interpreting a test result and finding a treatment plan within an after-visit summary. Discussion: When using a patient portal for the first time, participants with limited health literacy completed fewer tasks unassisted, had a higher prevalence of encountering barriers, took longer to complete tasks, and had more problems accurately interpreting medical information. Conclusion: Our findings suggest a strong need for tailored and accessible training and support to assist all vulnerable patients and/or caregivers with portal registration and use. Measuring the health literacy of a patient population might serve as a strong proxy for identifying patients who need the most support in using health technologies. PMID- 27402139 TI - Impact of computerized provider order entry (CPOE) on length of stay and mortality. AB - Objective: To examine changes in patient outcome variables, length of stay (LOS), and mortality after implementation of computerized provider order entry (CPOE). Materials and Methods: A 5-year retrospective pre-post study evaluated 66 186 patients and 104 153 admissions (49 683 pre-CPOE, 54 470 post-CPOE) at an academic medical center. Generalized linear mixed statistical tests controlled for 17 potential confounders with 2 models per outcome. Results: After controlling for covariates, CPOE remained a significant statistical predictor of decreased LOS and mortality. LOS decreased by 0.90 days, P < .0001. Mortality decrease varied by model: 1 death per 1000 admissions (pre = 0.006, post = 0.0005, P < .001) or 3 deaths (pre = 0.008, post = 0.005, P < .01). Mortality and LOS decreased in medical and surgical units but increased in intensive care units. Discussion: This study examined CPOE at multiple levels. Given the inability to randomize CPOE assignment, these results may only be applicable to the local setting. Temporal trends found in this study suggest that hospital-wide implementations may have impacted nursing staff and new residents. Differences in the results were noted at the patient care unit and room levels. These differences may partly explain the mixed results from previous studies. Conclusion: Controlling for confounders, CPOE implementation remained a statistically significant predictor of LOS and mortality at this site. Mortality appears to be a sensitive outcome indicator with regard to hospital-wide implementations and should be further studied. PMID- 27402140 TI - Online cancer communities as informatics intervention for social support: conceptualization, characterization, and impact. AB - Objectives: The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities. Target audience: The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial. Scope: The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients. PMID- 27402141 TI - How hepatitis C patients manage the treatment process of pegylated interferon and ribavirin therapy: a qualitative study. AB - BACKGROUND: Hepatitis C virus (HCV) infection is a global public health issue. Adequate treatment for hepatitis C patients is important, but anticipated side effects make patients fearful of receiving treatment. Little is known about the experiences of hepatitis C patients who have completed treatment with pegylated interferon and ribavirin. The purpose of this study was to explore the experiences of hepatitis C patients who had undergone therapy with pegylated interferon and ribavirin and gain an understanding of what factors contributed to completion of treatment. METHOD: This was a qualitative study with 21 adult hepatitis C patients purposively sampled from outpatient liver clinics of a medical university hospital in Taichung City, Taiwan. Participants had completed 6-12 months of therapy with pegylated interferon and ribavirin. Data were collected through individual, face-to-face, in-depth interviews conducted in the participants' homes from June-October 2013. Data were analysed using conventional content analysis. RESULTS: Data analysis revealed three themes that described the strategies employed to alleviate and ease symptoms and manage the processes involved: restructuring their lifestyle, adopting a positive attitude, and seeking support. CONCLUSION: Hepatitis C patients face many challenges during treatment with pegylated interferon and ribavirin. These findings provide knowledge that can be used in designing effective programs to help other Hepatitis C patients manage the side effects of pegylated interferon and ribavirin therapy, complete treatment and improve quality of life. PMID- 27402142 TI - Tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe chronic obstructive pulmonary disease: A meta-analysis. AB - PURPOSE: This meta-analysis was performed to compare the risks and benefits of combined treatment with tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe COPD. METHODS: A comprehensive search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) that compared formoterol plus tiotropium to tiotropium alone in COPD patients with a duration of at least 4 weeks. The cut-off date for the search was July 1, 2015. The odds ratio (OR) or mean difference (MD) was used to pool the results with 95% confidence intervals (CI). RESULTS: Eight randomized controlled trials were eligible for this meta-analysis. A significant improvement was observed among patients treated with tiotropium plus formoterol compared with tiotropium alone in the following spirometric indices: mean change in trough FEV1 (P = .02), trough FVC (P = .007), peak FEV1 (P < .00001), and peak FVC (P < .00001). A similar result was noted for the transitional dyspnea index (TDI) (MD 1.46; 95% CI 1.07-1.85) and a clinically significant change in TDI between the tiotropium plus formoterol and tiotropium alone groups (P < .00001). Moreover, a trend toward fewer adverse events was seen in the combination treatment group compared with the tiotropium group (OR .88; 95% CI .70-1.11), although this difference was not statistically significant. CONCLUSIONS: Compared with tiotropium alone, tiotropium in combination with formoterol improved lung function and the symptoms of dyspnea in stable moderate-to-severe COPD patients. Moreover, the combined treatment group tended to have fewer adverse events compared with the tiotropium treatment alone group. PMID- 27402144 TI - Early treatment for high-risk smouldering myeloma: has the time come? PMID- 27402143 TI - How does an integrated primary care approach for patients in deprived neighbourhoods impact utilization patterns? An explorative study. AB - BACKGROUND: To explore changes in utilization patterns for general practice (GP) and hospital care of people living in deprived neighbourhoods when primary care providers work in a more coherent and coordinated manner by applying an integrated approach. METHODS: We compared expected (based on consumption patterns of a health insurers' total population) and actual utilization patterns in a deprived Dutch intervention district in the city of Utrecht (Overvecht) with control districts 1 (Noordwest) and 2 (Kanaleneiland) over the period 2006-2011, when an integrated care approach was increasingly provided in the intervention district. Standardized insurance claims data were used to indicate use of GP care and hospital care. RESULTS: Our findings revealed that the utilization of total GP care increased more in the intervention district than in the control districts. And that the intervention district showed a more pronounced decreasing trend in total hospital use as compared to what was expected, in particular from 2008 onwards. In addition, we observed a change in type of GP care use in the intervention district in particular: the number of regular consultations, long consultations, GP home visits and evening, night and weekend consultations were increasingly higher than expected. The intervention district also showed the largest decrease between actual and expected use of ambulatory care, clinical care and 1-day hospitalizations. CONCLUSIONS: Utilization patterns for general practice and hospital care of people living in deprived districts may change when primary care professionals work in a more coherent and coordinated manner by applying a more 'comprehensive' integrated care approach. Results support the expectation that a comprehensive integrated care approach might eventually contribute to the future sustainability of healthcare systems. PMID- 27402146 TI - A prognostically relevant miRNA signature for epithelial ovarian cancer. PMID- 27402145 TI - Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up of a randomised, controlled, phase 3 trial. AB - BACKGROUND: The standard of care for smouldering multiple myeloma is observation. We did the QuiRedex study to compare early treatment with lenalidomide plus dexamethasone with observation in patients with high-risk smouldering multiple myeloma. Here we report the long-term follow-up results of the trial. METHODS: We did this open-label, randomised, controlled phase 3 study at 19 centres in Spain and three centres in Portugal. Patients aged 18 years or older with high-risk smouldering multiple myeloma were randomly assigned (1:1), via a computerised random number generator, to receive either early treatment with lenalidomide plus dexamethasone or observation, with dynamic balancing to maintain treatment balance within the two groups. Randomisation was stratified by time from diagnosis of smouldering multiple myeloma to study enrolment (<=6 months vs >6 months). Patients in the treatment group received nine 4-week induction cycles (lenalidomide 25 mg per day on days 1-21, plus dexamethasone 20 mg per day on days-1-4 and days 12-15), followed by maintenance therapy (lenalidomide 10 mg per day on days 1-21 of each 28-day cycle) up to 2 years. Group allocation was not masked from study investigators or patients. The primary endpoint was time from randomisation to progression to symptomatic myeloma. The primary analysis was based on the per-protocol population, restricted to patients who fulfilled the protocol in terms of eligibility. Safety assessments were based on the intention to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00480363. FINDINGS: Between Nov 8, 2007, and June 9, 2010, 125 patients were enrolled and underwent randomisation. 119 patients comprised the per-protocol population and were randomly assigned to receive either lenalidomide plus dexamethasone (n=57) or observation (n=62). The cutoff date for this update was June 30, 2015. Median follow-up for surviving patients was 75 months (IQR 67-85). Lenalidomide plus dexamethasone continued to provide a benefit on time to progression compared with observation (median time to progression not reached [95% CI 47 months-not reached] vs 23 months [16-31]; hazard ratio [HR] 0.24 [95% CI 0.14-0.41]; p<0.0001). Progression to multiple myeloma occurred in 53 (86%) of 62 patients in the observation group compared with 22 (39%) of 57 patients in the treatment group. At data cutoff, ten (18%) patients had died in the treatment group and 22 (36%) patients had died in the observation group; median overall survival from the time of study entry had not been reached in either group (95% CI 65 months-not reached vs 53 months-not reached; HR 0.43 [95% CI 0.21-0.92], p=0.024). Survival in patients who had received subsequent treatments at the time of progression to active disease did not differ between groups (HR 1.34 [95% CI 0.54-3.30]; p=0.50). The most frequently reported grade 3 adverse events in patients given lenalidomide plus dexamethasone were infection (four [6%]), asthenia (four [6%]), neutropenia (three [5%]), and skin rash (two [3%]); these events all occurred during induction therapy. No grade 4 adverse events occurred, but one (2%) patient in the lenalidomide plus dexamethasone group died from a respiratory infection during induction therapy The frequency of second primary malignancies was higher in patients in the treatment group than in those in the observation group (six [10%] of 62 patients vs one [2%] of 63 patients), but the cumulative risk of development did not differ significantly between the groups (p=0.070). INTERPRETATION: This study is, to our knowledge, the first randomised trial in which early treatment has been assessed in selected patients with high risk smouldering multiple myeloma. Positive results from ongoing trials would support the use of early treatment for patients with high-risk disease in the near future. FUNDING: Pethema (Spanish Program for the Treatment of Hematologic Diseases). PMID- 27402147 TI - Development and validation of a microRNA-based signature (MiROvaR) to predict early relapse or progression of epithelial ovarian cancer: a cohort study. AB - BACKGROUND: Risk of relapse or progression remains high in the treatment of most patients with epithelial ovarian cancer, and development of a molecular predictor could be a valuable tool for stratification of patients by risk. We aimed to develop a microRNA (miRNA)-based molecular classifier that can predict risk of progression or relapse in patients with epithelial ovarian cancer. METHODS: We analysed miRNA expression profiles in three cohorts of samples collected at diagnosis. We used 179 samples from a Multicenter Italian Trial in Ovarian cancer trial (cohort OC179) to develop the model and 263 samples from two cancer centres (cohort OC263) and 452 samples from The Cancer Genome Atlas epithelial ovarian cancer series (cohort OC452) to validate the model. The primary clinical endpoint was progression-free survival, and we adapted a semi-supervised prediction method to the miRNA expression profile of OC179 to identify miRNAs that predict risk of progression. We assessed the independent prognostic role of the model using multivariable analysis with a Cox regression model. FINDINGS: We identified 35 miRNAs that predicted risk of progression or relapse and used them to create a prognostic model, the 35-miRNA-based predictor of Risk of Ovarian Cancer Relapse or progression (MiROvaR). MiROvaR was able to classify patients in OC179 into a high-risk group (89 patients; median progression-free survival 18 months [95% CI 15-22]) and a low-risk group (90 patients; median progression-free survival 38 months [24-not estimable]; hazard ratio [HR] 1.85 [1.29-2.64], p=0.00082). MiROvaR was a significant predictor of progression in the two validation sets (OC263 HR 3.16, 95% CI 2.33-4.29, p<0.0001; OC452 HR 1.39, 95% CI 1.11-1.74, p=0.0047) and maintained its independent prognostic effect when adjusted for relevant clinical covariates using multivariable analyses (OC179: adjusted HR 1.48, 95% CI 1.03-2.13, p=0.036; OC263: adjusted HR 3.09 [2.24-4.28], p<0.0001; and OC452: HR 1.41 [1.11-1.79], p=0.0047). INTERPRETATION: MiROvaR is a potential predictor of epithelial ovarian cancer progression and has prognostic value independent of relevant clinical covariates. MiROvaR warrants further investigation for the development of a clinical-grade prognostic assay. FUNDING: AIRC and CARIPLO Foundation. PMID- 27402149 TI - Rates of and Experiences with Corneal Donation at the University Hospital Tubingen From 2002 To 2015. AB - BACKGROUND This study aimed to report the rates and experiences of corneal donation at the University Hospital Tubingen. MATERIAL AND METHODS Data from all cornea donors from January 2002 to December 2015 were analyzed. The rates of corneal donation were examined. From 2002 to 2008, an ophthalmic resident handled the corneal donor procurement in addition to his ward work. From 2009 to 2015, an ophthalmic resident handled the corneal donor procurement on a full-time basis. RESULTS Among the 10 260 deaths, consent for corneal donation was obtained in 892 cases. The mean annual corneal donation rate was 8.7 donors per 100 deaths (range: 2.0-17.8). The mean corneal donation rate in the first period without a full-time ophthalmic resident in the eye bank team was 4.0 donors per 100 deaths (95 % confidence interval [CI]: 1.0-6.9) and in the second period 12.3 donors per 100 deaths (95 % CI: 3.2-21.5) (P<0.0001). Comparing the periods before and after the modification of the eye bank team, the corneal donation rate was increased by more than 3 times. CONCLUSIONS Our study showed the influence of the eye banking team on the corneal donation rate. Modification of the eye bank team, by recruiting a full-time resident at a University Hospital with 1500 beds, increased the corneal donation rate by more than 3 times. It appears necessary to strengthen this team with sufficient staff levels to improve donor rates. PMID- 27402148 TI - Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor. AB - AIMS: Recent evidence indicates that weakly positive immunohistochemical staining of oestrogen receptor (ER) is not associated reliably with a luminal subtype, with the majority reclassified as basal-like by gene expression profile. In this study we assessed the capacity of recently identified immunohistochemical markers of basal-like subtype not dependent upon ER status - positive expression of nestin or loss of inositol polyphosphate-4-phosphatase (INPP4b) - to discriminate intrinsic subtypes, focusing on clinically problematic cases with weak ER positivity. METHODS AND RESULTS: Formalin-fixed paraffin-embedded blocks, enriched for large proportions of ER-negative and ER weakly positive breast cancers, were selected from two previous studies conducted in the period 2008-13 and used for (i) RNA extraction for 50-gene subtype predictor (PAM50) intrinsic subtyping and (ii) tissue microarray construction for immunohistochemical assessment of nestin and INPP4b. Fifty-eight cases were weakly positive for ER (Allred 3-5), among which 28 (48%) were assigned as basal-like by PAM50 gene expression. In these 58 cases, the nestin/INPP4b panel identified 23 basal-like cases with a positive predictive value of 87% [95% confidence interval (CI) 78 95%] and excluded luminal subtype with a negative predictive value of 95% (95% CI 88-100%). Weakly positive ER patients assigned as basal-like by nestin/INPP4b definition demonstrated a median survival time of 45.8 months, significantly lower than 65 months among other ER weakly positive cases (P = 0.012). CONCLUSIONS: Immunohistochemical assessment of nestin and INPP4b provides an accurate, accessible and inexpensive tool to identify basal-like breast cancer subtype in the clinically problematic setting of weak ER positivity. This panel identifies poor prognosis patients who might need strong considerations for non endocrine-based therapies. PMID- 27402150 TI - High Prevalence of Vitamin D Deficiency in Chronic Non-specific Musculoskeletal Pain. PMID- 27402151 TI - Oscar Wendell Jordan. PMID- 27402153 TI - Non-invasive prediction of catheter ablation outcome in persistent atrial fibrillation by fibrillatory wave amplitude computation in multiple electrocardiogram leads. AB - BACKGROUND: Catheter ablation (CA) of persistent atrial fibrillation (AF) is challenging, and reported results are capable of improvement. A better patient selection for the procedure could enhance its success rate while avoiding the risks associated with ablation, especially for patients with low odds of favorable outcome. CA outcome can be predicted non-invasively by atrial fibrillatory wave (f-wave) amplitude, but previous works focused mostly on manual measures in single electrocardiogram (ECG) leads only. AIM: To assess the long term prediction ability of f-wave amplitude when computed in multiple ECG leads. METHODS: Sixty-two patients with persistent AF (52 men; mean age 61.5+/ 10.4years) referred for CA were enrolled. A standard 1-minute 12-lead ECG was acquired before the ablation procedure for each patient. F-wave amplitudes in different ECG leads were computed by a non-invasive signal processing algorithm, and combined into a mutivariate prediction model based on logistic regression. RESULTS: During an average follow-up of 13.9+/-8.3months, 47 patients had no AF recurrence after ablation. A lead selection approach relying on the Wald index pointed to I, V1, V2 and V5 as the most relevant ECG leads to predict jointly CA outcome using f-wave amplitudes, reaching an area under the curve of 0.854, and improving on single-lead amplitude-based predictors. CONCLUSION: Analysing the f wave amplitude in several ECG leads simultaneously can significantly improve CA long-term outcome prediction in persistent AF compared with predictors based on single-lead measures. PMID- 27402152 TI - A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association. AB - Next generation sequencing (NGS) can globally interrogate the genetic composition of biological samples in an unbiased yet sensitive manner. The objective of this study was to utilize the capabilities of NGS to investigate the reported association between glioblastoma multiforme (GBM) and human cytomegalovirus (HCMV). A large-scale comprehensive virome assessment was performed on publicly available sequencing datasets from the Cancer Genome Atlas (TCGA), including RNA seq datasets from primary GBM (n = 157), recurrent GBM (n = 13), low-grade gliomas (n = 514), recurrent low-grade gliomas (n = 17), and normal brain (n = 5), and whole genome sequencing (WGS) datasets from primary GBM (n = 51), recurrent GBM (n = 10), and normal matched blood samples (n = 20). In addition, RNA-seq datasets from MRI-guided biopsies (n = 92) and glioma stem-like cell cultures (n = 9) were analyzed. Sixty-four DNA-seq datasets from 11 meningiomas and their corresponding blood control samples were also analyzed. Finally, three primary GBM tissue samples were obtained, sequenced using RNA-seq, and analyzed. After in-depth analysis, the most robust virus findings were the detection of papillomavirus (HPV) and hepatitis B reads in the occasional LGG sample (4 samples and 1 sample, respectively). In addition, low numbers of virus reads were detected in several datasets but detailed investigation of these reads suggest that these findings likely represent artifacts or non-pathological infections. For example, all of the sporadic low level HCMV reads were found to map to the immediate early promoter intimating that they likely originated from laboratory expression vector contamination. Despite the detection of low numbers of Epstein Barr virus reads in some samples, these likely originated from infiltrating B cells. Finally, human herpesvirus 6 and 7 aligned viral reads were identified in all DNA-seq and a few RNA-seq datasets but detailed analysis demonstrated that these were likely derived from the homologous human telomeric-like repeats. Other low abundance viral reads were detected in some samples but for most viruses, the reads likely represent artifacts or incidental infections. This analysis argues against associations between most known viruses and GBM or mengiomas. Nevertheless, there may be a low percentage association between HPV and/or hepatitis B and LGGs. PMID- 27402154 TI - Extending percutaneous left atrial appendage closure indications using the AMPLATZERTM Cardiac Plug device in patients with persistent left atrial appendage thrombus: The thrombus trapping technique. AB - BACKGROUND: Percutaneous left atrial appendage (LAA) closure has emerged as an alternative therapeutic option for the prevention of embolic stroke in high-risk patients with non-valvular atrial fibrillation. The presence of thrombus in the LAA is currently a contraindication to the procedure. AIM: To describe a modified LAA closure technique that allows a safe procedure in patients with LAA thrombus. METHODS: Between May 2013 and October 2014, LAA closure was performed in three patients with LAA thrombus (mean age 73.6+/-14 years; two men), using a modified technique that avoids manipulation of catheters or angiography in the LAA. RESULTS: Two patients had persistent thrombus despite appropriate antithrombotic therapy, while the other patient had a contraindication to systemic anticoagulation. The procedure was successful using the modified implantation technique in all patients. The implanted device was the AMPLATZERTM Cardiac Plug (St. Jude Medical, Minneapolis, MN, USA) in one patient and the AmuletTM (St. Jude Medical, Minneapolis, MN, USA) in two patients. No periprocedural complications occurred. After a mean follow-up of 8+/-2 months, no deaths or late complications were observed. CONCLUSIONS: Thrombus trapping is a feasible and effective technique for performing LAA occlusion in patients with thrombus within the LAA. This modification of the implantation technique may allow LAA closure indications to be extended to include patients with LAA thrombus, who were formerly considered unsuitable. PMID- 27402155 TI - Aeromicrobium camelliae sp. nov., isolated from Pu'er tea. PMID- 27402156 TI - Crush resistance and insufflation potential of poly(ethylene oxide)-based abuse deterrent formulations. AB - OBJECTIVES: This study was conducted to evaluate suitable methods of testing crush-resistant tablets composed largely of thermoplastic polymers. The objectives were, i) to evaluate the effect of thermal processes on crush resistance, ii) to develop test method(s) to indicate whether a crush-resistant tablet is susceptible to tampering by insufflation based on generated particle sizes, and iii) to find an appropriate analytical tool for discriminatory studies. METHODS: We investigated the crush-resistance properties of poly(ethylene oxide) (PEO) tablets using three manual and four electrical devices. PEO tablets were directly compressed or further heat-treated to mimic thermal manufacturing processes (i.e. hot-melt extrusion, sintering). Differential scanning calorimetry was also utilized to evaluate effect of thermal processes on polymer properties. RESULTS: Non-heat treated tablets were easily crushed by all methods. Heat-treated tablets were only susceptible to cryogenic grinding and high-powered domestic blender. Our results confirm that manual methods are not suitable for discriminatory study. CONCLUSIONS: Testing methods for crush resistance may not be applicable to all products nor allow control over all process factors. Notwithstanding, the use of high-powered electrical devices may be an effective discriminatory tool for testing heat treated PEO-based ADFs. PMID- 27402157 TI - Physiologically Based Pharmacokinetic Modeling of Palbociclib. AB - Palbociclib is an orally available CDK4/6 inhibitor. In humans, palbociclib undergoes metabolism mediated primarily by CYP3A and SULT2A1, and it is also a weak time-dependent CYP3A inhibitor. The objectives of the current study are to (1) develop a physiologically based pharmacokinetic (PBPK) model of palbociclib based on the in silico, in vitro, and in vivo pharmacokinetic data of palbociclib, (2) verify the PBPK model with clinical drug-drug interaction (DDI) results of palbociclib with strong CYP3A inhibitor (itraconazole), inducer (rifampin), and a sensitive CYP3A substrate (midazolam), and (3) predict the DDI risk of palbociclib with moderate/weak CYP3A inhibitors. The developed PBPK model adequately described the observed pharmacokinetics of palbociclib after administration of a single oral or intravenous dose of palbociclib. The model predicted DDIs of palbociclib with itraconazole, rifampin, and midazolam were consistent with the observed DDIs, with the discrepancies of the predicted vs observed AUCR and Cmax R within 20%, except for the AUC ratio of palbociclib with coadministration of rifampin. Using this final PBPK model, it was predicted that weak CYP3A inhibitors (fluoxetine and fluvoxamine) are anticipated to have negligible DDI risk with palbociclib, whereas moderate CYP3A inhibitors (diltiazem and verapamil) may increase plasma palbociclib AUC by ~40%. A moderate CYP3A inducer (efavirenz) may decrease plasma palbociclib AUC by ~40%. The established model is considered sufficiently robust for other applications in support of the continued development for palbociclib. PMID- 27402158 TI - Phospho-site mutants of the RNA Polymerase II C-terminal domain alter subtelomeric gene expression and chromatin modification state in fission yeast. AB - Eukaryotic gene expression requires that RNA Polymerase II (RNAP II) gain access to DNA in the context of chromatin. The C-terminal domain (CTD) of RNAP II recruits chromatin modifying enzymes to promoters, allowing for transcription initiation or repression. Specific CTD phosphorylation marks facilitate recruitment of chromatin modifiers, transcriptional regulators, and RNA processing factors during the transcription cycle. However, the readable code for recruiting such factors is still not fully defined and how CTD modifications affect related families of genes or regional gene expression is not well understood. Here, we examine the effects of manipulating the Y1S2P3T4S5P6S7 heptapeptide repeat of the CTD of RNAP II in Schizosaccharomyces pombe by substituting non-phosphorylatable alanines for Ser2 and/or Ser7 and the phosphomimetic glutamic acid for Ser7. Global gene expression analyses were conducted using splicing-sensitive microarrays and validated via RT-qPCR. The CTD mutations did not affect pre-mRNA splicing or snRNA levels. Rather, the data revealed upregulation of subtelomeric genes and alteration of the repressive histone H3 lysine 9 methylation (H3K9me) landscape. The data further indicate that H3K9me and expression status are not fully correlated, suggestive of CTD dependent subtelomeric repression mechansims that act independently of H3K9me levels. PMID- 27402159 TI - A part toolbox to tune genetic expression in Bacillus subtilis. AB - Libraries of well-characterised components regulating gene expression levels are essential to many synthetic biology applications. While widely available for the Gram-negative model bacterium Escherichia coli, such libraries are lacking for the Gram-positive model Bacillus subtilis, a key organism for basic research and biotechnological applications. Here, we engineered a genetic toolbox comprising libraries of promoters, Ribosome Binding Sites (RBS), and protein degradation tags to precisely tune gene expression in B. subtilis We first designed a modular Expression Operating Unit (EOU) facilitating parts assembly and modifications and providing a standard genetic context for gene circuits implementation. We then selected native, constitutive promoters of B. subtilis and efficient RBS sequences from which we engineered three promoters and three RBS sequence libraries exhibiting ~14 000-fold dynamic range in gene expression levels. We also designed a collection of SsrA proteolysis tags of variable strength. Finally, by using fluorescence fluctuation methods coupled with two-photon microscopy, we quantified the absolute concentration of GFP in a subset of strains from the library. Our complete promoters and RBS sequences library comprising over 135 constructs enables tuning of GFP concentration over five orders of magnitude, from 0.05 to 700 MUM. This toolbox of regulatory components will support many research and engineering applications in B. subtilis. PMID- 27402160 TI - A subset of replication-dependent histone mRNAs are expressed as polyadenylated RNAs in terminally differentiated tissues. AB - Histone proteins are synthesized in large amounts during S-phase to package the newly replicated DNA, and are among the most stable proteins in the cell. The replication-dependent (RD)-histone mRNAs expressed during S-phase end in a conserved stem-loop rather than a polyA tail. In addition, there are replication independent (RI)-histone genes that encode histone variants as polyadenylated mRNAs. Most variants have specific functions in chromatin, but H3.3 also serves as a replacement histone for damaged histones in long-lived terminally differentiated cells. There are no reported replacement histone genes for histones H2A, H2B or H4. We report that a subset of RD-histone genes are expressed in terminally differentiated tissues as polyadenylated mRNAs, likely serving as replacement histone genes in long-lived non-dividing cells. Expression of two genes, HIST2H2AA3 and HIST1H2BC, is conserved in mammals. They are expressed as polyadenylated mRNAs in fibroblasts differentiated in vitro, but not in serum starved fibroblasts, suggesting that their expression is part of the terminal differentiation program. There are two histone H4 genes and an H3 gene that encode mRNAs that are polyadenylated and expressed at 5- to 10-fold lower levels than the mRNAs from H2A and H2B genes, which may be replacement genes for the H3.1 and H4 proteins. PMID- 27402162 TI - Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli. AB - RNA ligases function pervasively across the three kingdoms of life for RNA repair, splicing and can be stress induced. The RtcB protein (also HSPC117, C22orf28, FAAP and D10Wsu52e) is one such conserved ligase, involved in tRNA and mRNA splicing. However, its physiological role is poorly described, especially in bacteria. We now show in Escherichia coli bacteria that the RtcR activated rtcAB genes function for ribosome homeostasis involving rRNA stability. Expression of rtcAB is activated by agents and genetic lesions which impair the translation apparatus or may cause oxidative damage in the cell. Rtc helps the cell to survive challenges to the translation apparatus, including ribosome targeting antibiotics. Further, loss of Rtc causes profound changes in chemotaxis and motility. Together, our data suggest that the Rtc system is part of a previously unrecognized adaptive response linking ribosome homeostasis with basic cell physiology and behaviour. PMID- 27402161 TI - Phosphorylation of Ku70 subunit by cell cycle kinases modulates the replication related function of Ku heterodimer. AB - The Ku protein, a heterodimer of Ku70 and Ku80, binds to chromosomal replication origins maximally at G1-phase and plays an essential role in assembly of origin recognition complex. However, the mechanism regulating such a critical periodic activity of Ku remained unknown. Here, we establish human Ku70 as a novel target of cyclin B1-Cdk1, which phosphorylates it in a Cy-motif dependent manner. Interestingly, cyclin E1- and A2-Cdk2 also phosphorylate Ku70, and as a result, the protein remains in a phosphorylated state during S-M phases of cell cycle. Intriguingly, the phosphorylation of Ku70 by cyclin-Cdks abolishes the interaction of Ku protein with replication origin due to disruption of the dimer. Furthermore, Ku70 is dephosphorylated in G1-phase, when Ku interacts with replication origin maximally. Strikingly, the over-expression of Ku70 with non phosphorylable Cdk targets enhances the episomal replication of Ors8 origin and induces rereplication in HeLa cells, substantiating a preventive role of Ku phosphorylation in premature and untimely licensing of replication origin. Therefore, periodic phosphorylation of Ku70 by cyclin-Cdks prevents the interaction of Ku with replication origin after initiation events in S-phase and the dephosphorylation at the end of mitosis facilitates its participation in pre replication complex formation. PMID- 27402163 TI - Comparison of Diffusion Metrics Obtained at 1.5T and 3T in Human Brain With Diffusional Kurtosis Imaging. AB - PURPOSE: To quantitatively compare diffusion metrics for human brain estimated with diffusional kurtosis imaging (DKI) at applied field strengths of 1.5 and 3T. MATERIALS AND METHODS: DKI data for brain were acquired at both 1.5 and 3T from each of six healthy volunteers using a twice-refocused diffusion-weighted imaging sequence. From these data, parametric maps of mean diffusivity (MD), axial diffusivity (D|| ), radial diffusivity (D? ), fractional anisotropy (FA), mean diffusional kurtosis (MK), axial kurtosis (K|| ), radial kurtosis (K? ), and kurtosis fractional anisotropy (KFA) were estimated. Comparisons of the results from the two field strengths were made for each metric using both Bland-Altman plots and linear regression to calculate coefficients of determination (R2 ) and best fit lines. RESULTS: Diffusion metrics measured at 1.5 and 3T were observed to be similar. Linear regression of the full datasets had coefficients of determination varying from a low of R2 = 0.86 for KFA to a high of R2 = 0.97 for FA. The slopes of the 3T vs. 1.5T best linear fits varied from 0.881 +/- 0.009 for KFA to 1.038 +/- 0.010 for D|| . From a Bland-Altman analysis of selected regions of interest, the mean differences of the metrics for the two field strengths were all found to be less than 6%, except for KFA, which showed the largest relative discrepancy of 10%. CONCLUSION: Diffusion metrics measured with DKI at 1.5 and 3T are strongly correlated and typically differ by only a few percent. The somewhat higher discrepancy for the KFA is argued to mainly reflect the effects of signal noise. This supports the robustness DKI results with respect to field strength. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:673-680. PMID- 27402164 TI - hsDNA groove binding, photocatalytic activity, and in vitro breast and colon cancer cell reducing function of greener SeNPs. AB - Selenium nanoparticles (SeNPs) have attracted great attention because of their superior optical properties and wide utilization in biological and biomedical studies. This paper reports an environmentally benign procedure of greener monodispersible SeNP synthesis using the reducing power of Trigonella foenum graecum extract, characterization and their protective effect against unfolded (Herring sperm DNA) hsDNA. We investigated the anti-cancer activity of SeNPs against MCF-7, MDA MB 435 and COLO-205 cells. The photocatalytic activity of SeNPs was investigated for the degradation of a Sunset Yellow FCF (SYFCF) dye using ultraviolet-B light. The reduction of the Se ion to SeNPs was monitored by ultraviolet-visible spectroscopy (UV-vis). The size and morphology of the SeNPs were characterized by high resolution transmission electron microscopy (HRTEM), X ray diffraction (XRD), and Dynamic Light Scattering (DLS). The SeNPs were stable, and the diameter was homogeneous at around 5-12 nm. Interactions of various concentrations of SeNPs with hsDNA were systematically investigated by UV-vis, fluorescence, circular dichroism (CD), polarimetry and FTIR spectroscopy under physiological conditions. The results from fluorescence spectroscopy indicated that SeNPs quenched the fluorescence intensity of hsDNA with increasing concentrations. The modified Stern-Volmer quenching rate constant Ksv, binding constant K and binding sites n at different temperatures and the corresponding thermodynamic parameters DeltaH degrees , DeltaG degrees and DeltaS degrees were calculated. Hoechst 33258 and methyl green (MG) site markers, melting experiment (Tm), viscosity measurements and sequence specificity verification by DNA bases clarified that SeNPs bind to hsDNA via a groove site. The rate of photocatalytic degradation of the SYFCF dye in the presence and absence of photocatalysts (SeNPs) was studied using UV-vis, the results showed appreciable degradation of the SYFCF dye. Our results suggested that nano Se can be used as a promising selenium species with potential application in cancer treatment. These nanoparticles were found to be the most active cytotoxic agent prepared in a new green synthesis manner, causing >50% inhibition of MCF-7, MDA MB-435 and COLO-205 cell proliferation at concentrations <10(-7) M. Hence these SeNPs could be recognized as promising materials for biomedical applications. PMID- 27402165 TI - Cavity-enhanced Raman microscopy of individual carbon nanotubes. AB - Raman spectroscopy reveals chemically specific information and provides label free insight into the molecular world. However, the signals are intrinsically weak and call for enhancement techniques. Here, we demonstrate Purcell enhancement of Raman scattering in a tunable high-finesse microcavity, and utilize it for molecular diagnostics by combined Raman and absorption imaging. Studying individual single-wall carbon nanotubes, we identify crucial structural parameters such as nanotube radius, electronic structure and extinction cross section. We observe a 320-times enhanced Raman scattering spectral density and an effective Purcell factor of 6.2, together with a collection efficiency of 60%. Potential for significantly higher enhancement, quantitative signals, inherent spectral filtering and absence of intrinsic background in cavity-vacuum stimulated Raman scattering render the technique a promising tool for molecular imaging. Furthermore, cavity-enhanced Raman transitions involving localized excitons could potentially be used for gaining quantum control over nanomechanical motion and open a route for molecular cavity optomechanics. PMID- 27402166 TI - Identification of Confirmatory Factor Analysis Models of Different Levels of Invariance for Ordered Categorical Outcomes. AB - This article considers the identification conditions of confirmatory factor analysis (CFA) models for ordered categorical outcomes with invariance of different types of parameters across groups. The current practice of invariance testing is to first identify a model with only configural invariance and then test the invariance of parameters based on this identified baseline model. This approach is not optimal because different identification conditions on this baseline model identify the scales of latent continuous responses in different ways. Once an invariance condition is imposed on a parameter, these identification conditions may become restrictions and define statistically non equivalent models, leading to different conclusions. By analyzing the transformation that leaves the model-implied probabilities of response patterns unchanged, we give identification conditions for models with invariance of different types of parameters without referring to a specific parametrization of the baseline model. Tests based on this approach have the advantage that they do not depend on the specific identification condition chosen for the baseline model. PMID- 27402167 TI - Primary ovarian carcinoid: A report of two cases and a decade registry. AB - OBJECTIVES: This study aims at reporting 2 cases of primary ovarian carcinoid tumor, and providing an adequate registry of such cases and how they were managed. METHODS: 2 female patients with primary ovarian carcinoid were diagnosed and treated in our center. Discussion of their presentation, pathology and treatment is entitled. Also a thorough search of all published registries and case reports of ovarian carcinoid was done with analysis of reported data. RESULTS: 164 cases of primary ovarian carcinoid tumor were detected since 2005 with the predominance of the insular variant. Carcinoid syndrome occurs in nearly 14% of these cases. Most of the cases were treated with hysterectomy. Unfortunately, the prognosis was not documented in most series. CONCLUSION: Primary ovarian carcinoid is a relatively rare disease with an indolent course and excellent outcome. Carcinoid syndrome, especially carcinoid heart disease may worsen the prognosis. Total abdominal hysterectomy with bilateral salpingo oophorectomy has been commonly used as the treatment of choice of primary ovarian carcinoid tumors. PMID- 27402168 TI - The Role of Knowledge on Genetic Counseling and Testing in Black Cancer Survivors at Increased Risk of Carrying a BRCA1/2 Mutation. AB - Genetic counseling and testing (GCT) for hereditary breast and ovarian cancers (HBOC) can inform treatment decisions in survivors. Black women at risk of HBOC have lower GCT engagement. There is limited data about Black survivors' experiences. The goals of this study were to: 1) examine the factors associated with HBOC knowledge and 2) assess the impact of knowledge on GCT engagement in a sample of Black survivors at risk of HBOC. Fifty Black at-risk breast/ovarian cancer survivors participated in a telephone-based survey. GCT use was measured across a continuum (awareness, referral, and use). The primary predictor variable was HBOC knowledge. Other clinical, socio-demographic, and psychosocial variables were included. Multiple linear and ordinal regression models (knowledge as the outcome and GCT as the outcome) assessed the predictors of knowledge and GCT engagement. Less than half (48 %) of survivors were referred to or used GCT services. Knowledge was moderate (M = 7.78, SD = 1.61). In the multivariable analysis, lower age (beta = -.34, p = .01) and lower stage (beta = -.318, p = .017) were associated with higher knowledge. Higher knowledge (beta = .567, p = .006) and higher self-efficacy (beta = .406, p = .001) were significantly associated with GCT engagement. Future interventions directed at increasing knowledge, self-efficacy, and improving the referral process are warranted. PMID- 27402169 TI - Phenylboronic acid modified solid-phase extraction column: Preparation, characterization, and application to the analysis of amino acids in sepia capsule by removing the maltose. AB - Maltose, a common auxiliary material of pharmaceutical preparation, may disturb the analysis of total amino acids in sepia capsule by aldolization. Therefore, it is necessary to remove the maltose through a convenient method. In this work, a phenylboronic acid modified solid-phase extraction column has been synthesized and used to remove the maltose. The materials were synthesized by one step "thiol ene" reaction and the parameters of the column such as absorption capacity, recovery, and absorption specificity have been investigated. The results showed the column (0.5 cm of length * 0.5 cm of inner diameter) can absorb 4.6 mg maltose with a linear absorption and absorption specificity. Then this technique was applied in the quantification of amino acids in sepia capsule. After the optimization of the method, four kinds of amino acids, which were the most abundant, were quantified by high-performance liquid chromatography with diode array detection. The amounts of the four kinds of amino acids are 1.5~2 times more than that without the treatment of solid-phase extraction column, which almost overcomes the influence of the maltose. All the results indicate that the phenylboronic acid modified solid-phase extraction column can successfully help to accurately quantify the total amino acids in sepia capsule. PMID- 27402170 TI - Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations. AB - BACKGROUND: Patients with autosomal or X-linked Alport syndrome (AS) with heterozygous mutations in type IV collagen genes have a 1-20 % risk of progressing to end-stage renal disease during their lifetime. We evaluated the long-term renal outcome of patients at risk of progressive disease (chronic kidney disease stages 1-4) with/without nephroprotective therapy. METHODS: This was a prospective, non-interventional, observational study which included data from a 4-year follow-up of AS patients with heterozygous mutations whose datasets had been included in an analysis of the 2010 database of the European Alport Registry. Using Kaplan-Meier estimates and logrank tests, we prospectively analyzed the updated datasets of 52 of these patients and 13 new datasets (patients added to the Registry after 2011). The effects of therapy, extrarenal symptoms and inheritance pattern on renal outcome were analyzed. RESULTS: The mean prospective follow-up was 46 +/- 10 months, and the mean time on therapy was 8.4 +/- 4.4 (median 7; range 2-18) years. The time from the appearance of the first symptom to diagnosis was 8.1 +/- 14.2 (range 0-52) years. At the time of starting therapy, 5.4 % of patients had an estimated glomerular filtration rate of <60 ml/min, 67.6 % had proteinuria and 27.0 % had microalbuminuria. Therapeutic strategies included angiotensin-converting enzymer inhibitors (97.1 %), angiotensin receptor antagonists (1 patient), dual therapy (11.8 %) and statins (8.8 %). Among patients included in the prospective dataset, prevented the need for dialysis. Among new patients, no patient at risk for renal failure progressed to the next disease stage after 4 years follow-up; three patients even regressed to a lower stage during therapy. CONCLUSIONS: Treatment with blockers of the renin-angiotensin-aldosterone system prevents progressive renal failure in AS patients with heterozygous mutations in the genes causing AS. Considerable numbers of aging AS patients on dialysis may have heterozygous mutations in these genes (present in 1 % of total population) as underlying disease. Hence, greater alertness towards timely diagnosis and therapy has the potential to prevent progressive renal failure in most-if not all-AS patients with heterozygous mutations in the causal genes. PMID- 27402171 TI - Altered expression of the bZIP transcription factor DRINK ME affects growth and reproductive development in Arabidopsis thaliana. AB - Here we describe an uncharacterized gene that negatively influences Arabidopsis growth and reproductive development. DRINK ME (DKM; bZIP30) is a member of the bZIP transcription factor family, and is expressed in meristematic tissues such as the inflorescence meristem (IM), floral meristem (FM), and carpel margin meristem (CMM). Altered DKM expression affects meristematic tissues and reproductive organ development, including the gynoecium, which is the female reproductive structure and is determinant for fertility and sexual reproduction. A microarray analysis indicates that DKM overexpression affects the expression of cell cycle, cell wall, organ initiation, cell elongation, hormone homeostasis, and meristem activity genes. Furthermore, DKM can interact in yeast and in planta with proteins involved in shoot apical meristem maintenance such as WUSCHEL, KNAT1/BP, KNAT2 and JAIBA, and with proteins involved in medial tissue development in the gynoecium such as HECATE, BELL1 and NGATHA1. Taken together, our results highlight the relevance of DKM as a negative modulator of Arabidopsis growth and reproductive development. PMID- 27402174 TI - Evaluation of calibration-free concentration analysis provided by BiacoreTM systems. AB - Surface Plasmon Resonance biosensors measure the interaction between a molecule in solution and its interaction partner attached to a sensor surface. Under certain conditions, the observed binding rate can be used directly to obtain the concentration of the molecule in solution, without the use of any standard. This type of assay is referred to as Calibration Free Concentration Analysis, CFCA. By examining experimental conditions, including immobilization levels and temperature, for a range of analytes, and by using global analysis of several sample dilutions, conditions that gave the most robust results were identified. These conditions provided the concentration values that were on average ~15% lower than those obtained using other methods. The accuracy of the concentration determined may be related to how the analyte is distributed in the dextran matrix and to its distance from the gold surface, and may thereby depend on the conversion of the SPR signal to mass. A good precision of CFCA, ~8% (n = 21), was demonstrated when this method was used to efficiently guide purification procedures of Interferon alpha-2a. In this paper, the theory behind CFCA and the future developments, as well as the application of CFCA for absolute and relative concentration measurements (including the assessment of the potency of a biotherapeutic medicine) are discussed, and new evaluation tools that broaden the range of applications, are introduced. PMID- 27402172 TI - Neutropenia in the Elderly: A Rheumatology Perspective. AB - The majority of rheumatic diseases are chronic and require long-term use of disease-modifying agents to confer the best chance of controlling the disease. A significant proportion of these drugs have a risk, albeit small, of potentially serious side effects, such as neutropenia; therefore, there has been an understandable concern over the use of potentially toxic rheumatic drugs in the elderly. Factors that may contribute to this concern include age, pre-existing co morbidities, polypharmacy, difficulty in monitoring side effects, and patient perception. The risk of using such medication needs to be balanced with their benefits in controlling chronic disease. This review discusses how rheumatic disease and anti-rheumatic medication are associated with neutropenia in an older age group. Of the rheumatic diseases, we give special focus to rheumatoid arthritis and the use of methotrexate, as well as touching on management considerations in neutropenia. PMID- 27402175 TI - Deconvolution of complex differential scanning calorimetry profiles for protein transitions under kinetic control. AB - A frequent outcome in differential scanning calorimetry (DSC) experiments carried out with large proteins is the irreversibility of the observed endothermic effects. In these cases, DSC profiles are analyzed according to methods developed for temperature-induced denaturation transitions occurring under kinetic control. In the one-step irreversible model (native -> denatured) the characteristics of the observed single-peaked endotherm depend on the denaturation enthalpy and the temperature dependence of the reaction rate constant, k. Several procedures have been devised to obtain the parameters that determine the variation of k with temperature. Here, we have elaborated on one of these procedures in order to analyze more complex DSC profiles. Synthetic data for a heat capacity curve were generated according to a model with two sequential reactions; the temperature dependence of each of the two rate constants involved was determined, according to the Eyring's equation, by two fixed parameters. It was then shown that our deconvolution procedure, by making use of heat capacity data alone, permits to extract the parameter values that were initially used. Finally, experimental DSC traces showing two and three maxima were analyzed and reproduced with relative success according to two- and four-step sequential models. PMID- 27402173 TI - Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors. AB - Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ion channels regulated by ATP. We recently demonstrated that P2X4R knockout (KO) mice exhibited deficits in sensorimotor gating, social interaction, and ethanol drinking behavior. Dopamine (DA) dysfunction may underlie these behavioral changes, but there is no direct evidence for P2X4Rs' role in DA neurotransmission. To test this hypothesis, we measured markers of DA function and dependent behaviors in P2X4R KO mice. P2X4R KO mice exhibited altered density of pre-synaptic markers including tyrosine hydroxylase, dopamine transporter; post-synaptic markers including dopamine receptors and phosphorylation of downstream targets including dopamine and cyclic-AMP regulated phosphoprotein of 32 kDa and cyclic-AMP-response element binding protein in different parts of the striatum. Ivermectin, an allosteric modulator of P2X4Rs, significantly affected dopamine and cyclic AMP regulated phosphoprotein of 32 kDa and extracellular regulated kinase1/2 phosphorylation in the striatum. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Using the 6-hydroxydopamine model of DA depletion, P2X4R KO mice exhibited an attenuated levodopa (L-DOPA) induced motor behavior, whereas ivermectin enhanced this behavior. Collectively, these findings identified an important role for P2X4Rs in maintaining DA homeostasis and illustrate how this association is important for CNS functions including motor control and sensorimotor gating. We propose that P2X4 receptors (P2X4Rs) regulate dopamine (DA) homeostasis and associated behaviors. Pre synaptic and post-synaptic DA markers were significantly altered in the dorsal and ventral striatum of P2X4R KO mice, implicating altered DA neurotransmission. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Ivermectin (IVM), a positive modulator of P2X4Rs, enhanced levodopa (L-DOPA) induced motor behavior. These studies highlight potential interactions between P2X4Rs and DA system. PMID- 27402176 TI - Determination of (2)H-enrichment of rat brain interstitial fluid and rat plasma by headspace-gas-chromatography - quadrupole-mass-spectrometry. AB - (2)H2O as nonradioactive, stable marker substance is commonly used in preclinical and clinical studies and the precise determination of (2)H2O concentration in biological samples is crucial. However, aside from isotope ratio mass spectrometry (IRMS), only a very limited number of methods to accurately measure the (2)H2O concentration in biological samples are routinely established until now. In this study, we present a straightforward method to accurately measure (2)H-enrichment of rat brain interstitial fluid (ISF) and rat plasma to determine the relative recovery of a cerebral open flow microperfusion (cOFM) probe, using headspace-gas-chromatography - quadrupole-mass-spectrometry. This method is based on basic-catalyzed hydrogen/deuterium exchange in acetone and detects the (2)H labelled acetone directly by the headspace GC-MS. Small sample volumes and limited number of preparation steps make this method highly competitive. It has been fully validated. (2)H enriched to 8800 ppm in plasma showed an accuracy of 98.9% and %Relative Standard Deviation (RSD) of 3.1 with n = 18 over three days and with two operators. Similar performance was obtained for cerebral ISF enriched to 1100 ppm (accuracy: 96.5%, %RSD: 3.1). With this highly reproducible method we demonstrated the successful employment of (2)H2O as performance marker for a cOFM probe. PMID- 27402177 TI - Electrochemical detection of uric acid via uricase-immobilized graphene oxide. AB - Measurement of the uric acid level in the body can be improved by biosensing with respect to the accuracy, sensitivity and time consumption. This study has reported the immobilization of uricase onto graphene oxide (GO) and its function for electrochemical detection of uric acid. Through chemical modification of GO using 1-ethyl-3-(dimethylaminopropyl) carbodiimide (EDC) and N hydroxysulfosuccinimide (NHS) as cross-linking reagents, the enzyme activity of the immobilized uricase was much comparable to the free enzyme with 88% of the activity retained. The modified GO-uricase (GOU) was then subjected to electrocatalytic detection of uric acid (UA) via cyclic voltammetry (CV). For that reason, a glassy carbon electrode (GCE) was modified by adhering the GO along with the immobilized uricase to facilitate the redox reaction between the enzyme and the substrate. The modified GOU/GCE outperformed a bare electrode through the electrocatalytic activity with an amplified electrical signal for the detection of UA. The electrocatalytic response showed a linear dependence on the UA concentration ranging from 0.02 to 0.49 mM with a detection limit of 3.45 MUM at 3sigma/m. The resulting biosensor also exhibited a high selectivity towards UA in the presence of other interference as well as good reproducibility. PMID- 27402178 TI - Large fragment deletion using a CRISPR/Cas9 system in Saccharomyces cerevisiae. AB - Large chromosomal modifications have been performed in natural and laboratory evolution studies and hold tremendous potential for use in foundational research, medicine, and biotechnology applications. Recently, the type II bacterial Clustered Regularly Interspaced Short Palindromic Repeat and CRISPR-associated (CRISPR/Cas9) system has emerged as a powerful tool for genome editing in various organisms. In this study, we applied the CRISPR/Cas9 system to preform large fragment deletions in Saccharomyces cerevisiae and compared the performance activity to that of a traditional method that uses the Latour system. Here we report in S. Cerevisiae the CRIPR/Cas9 system has been used to delete fragments exceeding 30 kb. The use of the CRISPR/Cas9 system for generating chromosomal segment excision showed some potential advantages over the Latour system. All the results indicated that CRISPR/Cas9 system was a rapid, efficient, low-cost, and versatile method for genome editing and that it can be applied in further studies in the fields of biology, agriculture, and medicine. PMID- 27402179 TI - Thyroid surgery at a volunteer program in Sub-Saharan Africa. AB - INTRODUCTION: The aim of this study is to demonstrate our experience at a volunteer surgical program in Cameroon, which is of special interest given to the inability to adopt international treatment guidelines for thyroid surgery in areas of limited resources due to the lack of preoperative testing and to the difficulty to obtain sustitutive hormonal treatment. METHODS: This is a prospective observational study that includes 16 cases of thyroid surgery in Dschang (Cameroon) during June 2015. The patients were previously selected by a local medical team. All patients were black, 15 women and one man, with a mean age of 41 years. The surgical technique used for the removal of unilateral disease was hemithyroidectomy with isthmectomy and bilateral subtotal thyroidectomy for bilateral disease. RESULTS: Five subtotal thyroidectomies, 9hemithyroidectomies and 2isthmectomies were performed. Prethyroid muscles were divided only in one case. We visualized 86% of the parathyroid glands and 84% of the recurrent laryngeal nerves. The main complications observed were one symptomatic cervical haematoma that required reoperation and 2surgical wound infections. There were no clinical episodes of hypocalemia or recurrent nerve lesion. The mean length of stay was 2.3 days. At follow-up, all bilateral thyroidectomies developed high TSH levels. CONCLUSIONS: Thyroid surgery is safe in developing countries adopting protocols and techniques we use in our environment (avoiding total thyroidectomy). Bilateral thyroidectomies should not be performed unless functional studies are available in the follow-up and a thyroid hormone supplement stock guaranteed whenever necessary. PMID- 27402180 TI - Fluid-flow-templated self-assembly of calcium carbonate tubes in the laboratory and in biomineralization: The tubules of the watering-pot shells, Clavagelloidea. AB - We show with laboratory experiments that self-assembled mineral tube formation involving precipitation around a templating jet of fluid - a mechanism well-known in the physical sciences from the tubular growth of so-called chemical gardens - functions with carbonates, and we analyse the microstructures and compositions of the precipitates. We propose that there should exist biological examples of fluid flow-templated tubes formed from carbonates. We present observational and theoretical modelling evidence that the complex structure of biomineral calcium carbonate tubules that forms the 'rose' of the watering-pot shells, Clavagelloidea, may be an instance of this mechanism in biomineralization. We suggest that this is an example of self-organization and self-assembly processes in biomineralization, and that such a mechanism is of interest for the production of tubes as a synthetic biomaterial. STATEMENT OF SIGNIFICANCE: The work discussed in the manuscript concerns the self-assembly of calcium carbonate micro tubes and nano-tubes under conditions of fluid flow together with chemical reaction. We present the results of laboratory experiments on tube self-assembly together with theoretical calculations. We show how nature may already be making use of this process in molluscan biomineralization of the so-called watering-pot shells, and we propose that we may be able to take advantage of the formation mechanism to produce synthetic biocompatible micro- and nano-tubes. PMID- 27402181 TI - Multifunctional biomaterials from the sea: Assessing the effects of chitosan incorporation into collagen scaffolds on mechanical and biological functionality. AB - Natural biomaterials such as collagen show promise in tissue engineering applications due to their inherent bioactivity. The main limitation of collagen is its low mechanical strength and somewhat unpredictable and rapid degradation rate; however, combining collagen with another material, such as chitosan, can reinforce the scaffold mechanically and may improve the rate of degradation. Additionally, the high cost and the risk of prion transmission associated with mammal-derived collagen has prompted research into alternative sources such as marine-origin collagen. In this context, the overall goal of this study was to determine if the incorporation of chitosan into collagen scaffolds could improve the mechanical and biological properties of the scaffold. In addition the study assessed if collagen, derived from salmon skin (marine), can provide an alternative to collagen derived from bovine tendon (mammal) for tissue engineering applications. Scaffold architecture and mechanical properties were assessed as well as their ability to support mesenchymal stem cell growth and differentiation. Overall, the addition of chitosan to bovine and salmon skin derived collagen scaffolds improved the mechanical properties, increasing the compressive strength, swelling ratio and prolonged the degradation rate. Mesenchymal stem cell (MSC) attachment and proliferation was most improved on the bovine-derived collagen scaffold containing a 75:25 ratio of collagen:chitosan, and when MSC osteogenic and chondrogenic potential on the scaffold was assessed, a significant increase in calcium production (p<0.001) and sulfated glycosaminoglycan (sGAG) production (p<0.001) was observed respectively. Regardless of chitosan content, the bovine-derived collagen scaffolds out performed the salmon skin-derived collagen scaffolds, displaying a larger pore size and higher percentage porosity, more regular architecture, higher compressive modulus, a greater capacity for water uptake and allowed for more MSC proliferation and differentiation. This versatile scaffold incorporating the marine biomaterial chitosan show great potential as appropriate platforms for promoting orthopaedic tissue repair while the use of salmon skin-derived collagen may be more suitable in the repair of soft tissues such as skin. STATEMENT OF SIGNIFICANCE: Collagen is commonly used in tissue engineering due to its biocompatibility; however, it has low mechanical strength and an unpredictable degradation rate. In addition, high cost and risk of prion transmission associated with mammalian-derived collagen has prompted research into alternative collagen sources, namely, marine-derived collagen. In this study, scaffolds made from salmon-skin collagen were compared to the more commonly used bovine-derived collagen with a focus on orthopaedic applications. To improve the mechanical properties of these scaffolds, another marine biomaterial, chitosan, was added to produce scaffolds with increased mechanical stability. The collagen-chitosan composites were also shown to support mesenchymal stem cell differentiation towards both bone and cartilage tissue. This multi-functional scaffold therefore has potential in both bone and cartilage regeneration applications. PMID- 27402182 TI - The evolution of reproductive diversity in Afrobatrachia: A phylogenetic comparative analysis of an extensive radiation of African frogs. AB - The reproductive modes of anurans (frogs and toads) are the most diverse of terrestrial vertebrates, and a major challenge is identifying selective factors that promote the evolution or retention of reproductive modes across clades. Terrestrialized anuran breeding strategies have evolved repeatedly from the plesiomorphic fully aquatic reproductive mode, a process thought to occur through intermediate reproductive stages. Several selective forces have been proposed for the evolution of terrestrialized reproductive traits, but factors such as water systems and co-evolution with ecomorphologies have not been investigated. We examined these topics in a comparative phylogenetic framework using Afrobatrachian frogs, an ecologically and reproductively diverse clade representing more than half of the total frog diversity found in Africa (~400 species). We infer direct development has evolved twice independently from terrestrialized reproductive modes involving subterranean or terrestrial oviposition, supporting evolution through intermediate stages. We also detect associations between specific ecomorphologies and oviposition sites, and demonstrate arboreal species exhibit an overall shift toward using lentic water systems for breeding. These results indicate that changes in microhabitat use associated with ecomorphology, which allow access to novel sites for reproductive behavior, oviposition, or larval development, may also promote reproductive mode diversity in anurans. PMID- 27402183 TI - Xbox KinectTM based rehabilitation as a feasible adjunct for minor upper limb burns rehabilitation: A pilot RCT. AB - INTRODUCTION: Rehabilitation following burns is integral to improving physical and psychological outcomes. Interactive video game consoles are emerging as therapeutic adjuncts due to their ease of use, affordability, and interactive gameplay. The Xbox KinectTM has advantage over similar consoles, with controller free interaction utilising three dimensional motion capture software. Player movements during gameplay have been shown to be comparable to completing daily tasks and therefore the Xbox KinectTM has potential for use as a rehabilitation tool. AIM: The objectives of this pilot study were to compare the efficacy of the Xbox KinectTM with conventional physiotherapy as an adjunctive tool to promote activity and, to explore their efficacy in influencing functionality and pain. METHOD: A randomised controlled clinical trial design was used. Intervention group participants were asked to complete two daily 30min exercise sessions consisting of 15min of self-directed physiotherapy exercise followed by 15min of Xbox KinectTM activities, based on location of burn. Control group participants were asked to complete two daily 30min exercise sessions of self-directed physiotherapy exercises involving two 15min sets of exercises, standardised for location of burn. Participants were recruited for a maximum of 7 days. Outcomes assessed included daily activity time, treatment satisfaction, upper limb disability, pain, and self-reported fear of movement (kinesiophobia). RESULTS: A sample of 30 burn patients admitted to Royal Perth Hospital was randomised into intervention and control groups. The intervention group demonstrated significantly greater total activity time compared to control group (median 49.4 and 26.7min respectively, p<0.0001), irrespective of total burns surface area (TBSA). Significantly greater satisfaction scores were also demonstrated in the intervention group compared to controls (median 8.53 vs 7.8 respectively, p<0.0001). There was no evidence to support differences between group measures for upper limb disability, pain and fear avoidance of movement. CONCLUSION: The Xbox KinectTM is a useful tool in increasing rehabilitation exercise time and patient satisfaction compared to conventional physiotherapy without indication of concurrent negative effects on patient recovery. PMID- 27402184 TI - The apportionment of tooth size and its implications in Australopithecus sediba versus other Plio-pleistocene and recent African hominins. AB - OBJECTIVES: Australopithecus sediba is characterized further by providing formerly unpublished and refined mesiodistal and buccolingual crown measurements in the MH1 and MH2 specimens. After size correction, these data were compared with those in other fossil and recent samples to facilitate additional insight into diachronic hominin affinities. MATERIALS AND METHODS: Six comparative samples consist of fossil species: A. africanus, A. afarensis, Homo habilis, Paranthropus robustus, P. boisei, and H. erectus. Others comprise H. sapiens and Pan troglodytes. Re-estimates of "actual" dimensions in damaged A. sediba teeth were effected through repeated measurements by independent observers. X-ray synchrotron microtomography allowed measurement of crowns obscured by matrix and noneruption. Tooth size apportionment analysis, an established technique for intraspecific comparisons, was then applied at this interspecific level to assess phenetic affinities using both within- and among-group data. RESULTS: Comparison of these highly heritable dimensions identified a general trend for smaller posterior relative to larger anterior teeth (not including canines), contra Paranthropus, that allies A. sediba with other australopiths and Homo; however, specific reductions and/or shape variation in the species' canines, third premolars, and anterior molars relative to the other teeth mirror the patterning characteristic of Homo. DISCUSSSION: Of all samples, including east African australopiths, A. sediba appears most like H. habilis, H. erectus and H. sapiens regarding how crown size is apportioned along the tooth rows. These findings parallel those in prior studies of dental and other skeletal data, including several that suggest A. sediba is a close relative of, if not ancestral to, Homo. PMID- 27402185 TI - Lessons Learned From Dissemination of Evidence-Based Interventions for HIV Prevention. AB - In 1999, IOM issued a report that recommended that the Centers for Disease Control and Prevention should disseminate evidence-based HIV prevention interventions (EBIs) to be implemented by health departments, community-based organizations, drug treatment centers, and clinics. Based on these recommendations, the Diffusion of Effective Behavioral Interventions Project was initiated in 2000 and began disseminating interventions into public health practice. For 15 years, the Centers for Disease Control and Prevention has disseminated 29 EBIs to more than 11,300 agencies. Lessons were identified during the 15 years of implementation regarding successful methods of dissemination of EBIs. Lessons around selecting interventions for dissemination, developing a dissemination infrastructure including a resource website (https://effectiveinterventions.cdc.gov), and engagement with stakeholders are discussed. A continuous development approach ensured that intervention implementation materials, instructions, and technical assistance were all tailored to the needs of end users, focus populations, and agency capacities. Six follow-up studies demonstrated that adopters of EBIs were able to obtain comparable outcomes to those of the original efficacy research. The Diffusion of Effective Behavioral Interventions Project may offer guidance for other large, national, evidence-based public health dissemination projects. PMID- 27402186 TI - U.S. Preventive Services Task Force Approach to Child Cognitive and Behavioral Health. AB - An important component of routine preventive care for children is the monitoring of growth and development. Although cognitive, affective, and behavioral health problems are commonly encountered in pediatric primary care, there is debate around issues related to early detection of significant problems of this type, including the accuracy of screening and the benefits and harms of early diagnosis and treatment. The U.S. Preventive Services Task Force makes recommendations regarding clinical preventive services for primary care clinicians based on the best available scientific evidence. The Task Force has found important gaps related to the validity of commonly used screening tools and significant gaps related to the evidence regarding early treatment. This review describes the meaning of the grades used by the Task Force, how these grades are determined, and the grades assigned to childhood cognitive, affective, and behavioral health recommendations. The review summarizes common themes in the evidence gaps and the future research necessary to advance the field and improve child health outcomes. PMID- 27402187 TI - Functional and cellular consequences of covalent target protein modification by furan in rat liver. AB - Furan hepatotoxicity is thought to be linked to covalent binding of its reactive metabolite, cis-2-butene-1,4-dial, to hepatic proteins critical for cell homeostasis and survival. We previously identified 61 putative furan target proteins, which participate in various cellular processes including carbohydrate metabolism, fatty acid beta-oxidation, adenosine triphosphate (ATP) synthesis, protein folding and maintenance of redox homeostasis. To further investigate the biological significance of target protein modification, this study was designed to determine the impact of furan on the activity of key target enzymes involved in glycolysis, beta-oxidation, ATP synthesis, and redox regulation in rat liver, and to link these functional changes to alterations in cellular processes. While cis-2-butene-1,4-dial inhibited thioredoxin 1 (Txn1) in a cell-free assay, in livers of rats treated with a single high dose of furan Txn1 activity was markedly increased due to rapid up-regulation of Txn1 mRNA expression. Significant inhibition of glyceraldehyde-3-phosphate dehydrogenase and metabolic changes consistent with blocked glycolytic breakdown of glucose were observed in rat liver in response to a single high dose of furan. In contrast, furan treatment resulted in increased activity of enoyl-CoA hydratase and enhanced production of ketone bodies, indicative of increased utilization of fatty acids as energy source. Consistent with changes in TCA cycle metabolites, furan treatment resulted in a reduction of succinate dehydrogenase activity, supporting mitochondrial dysfunction as a critical event in furan toxicity. No significant changes in target protein function were observed following repeated administration of furan at lower dose (0.1 and 0.5mg/kg bw for 4 weeks) closer to estimated human exposure to furan via food. Although the relative contribution of furan mediated alterations in metabolic pathways and antioxidant defense to the overall toxic response to furan, including considerations of dose and time, remains to be established, our work contributes to mapping biological processes and toxicity pathways modulated by reactive electrophiles. PMID- 27402188 TI - Caenorhabditis elegans homologue of Prox1/Prospero is expressed in the glia and is required for sensory behavior and cold tolerance. AB - The Caenorhabditis elegans (C. elegans) amphid sensory organ contains only 4 glia like cells and 24 sensory neurons, providing a simple model for analyzing glia or neuron-glia interactions. To better characterize glial development and function, we carried out RNA interference screening for transcription factors that regulate the expression of an amphid sheath glial cell marker and identified pros-1, which encodes a homeodomain transcription factor homologous to Drosophila prospero/mammalian Prox1, as a positive regulator. The functional PROS-1::EGFP fusion protein was localized in the nuclei of the glia and the excretory cell but not in the amphid sensory neurons. pros-1 deletion mutants exhibited larval lethality, and rescue experiments showed that pros-1 and human Prox1 transgenes were able to rescue the larval lethal phenotype, suggesting that pros-1 is a functional homologue of mammalian Prox1, at least partially. We further found that the structure and functions of sensory neurons, such as the morphology of sensory endings, sensory behavior and sensory-mediated cold tolerance, appeared to be affected by the pros-1 RNAi. Together, our results show that the C. elegans PROS-1 is a transcriptional regulator in the glia but is involved not only in sensory behavior but also in sensory-mediated physiological tolerance. PMID- 27402190 TI - Ultramicronized palmitoylethanolamide (PEA-um((r))) in the treatment of idiopathic pulmonary fibrosis. AB - Pulmonary fibrosis is a chronic condition characterized by progressive scarring of lung parenchyma. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (PEA-um((r))), an endogenous fatty acid amide, in mice subjected to idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis was induced in male mice by a single intratracheal administration of saline with bleomycin sulphate (1mg/kg body weight) in a volume of 100MUL. PEA-um((r)) was injected intraperitoneally at 1, 3 or 10mg/kg 1h after bleomycin instillation and daily thereafter. Animals were sacrificed after 7 and 21days by pentobarbitone overdose. One cohort of mice was sacrificed after seven days of bleomycin administration, followed by bronchoalveloar lavage and determination of myeloperoxidase activity, lung edema and histopathology features. In the 21-day cohort, mortality was assessed daily, and surviving mice were sacrificed followed by the above analyses together with immunohistochemical localization of CD8, tumor necrosis factor-alpha, CD4, interleukin-1beta, transforming growth factor-beta, inducible nitric oxide synthase and basic fibroblast growth factor. Compared to bleomycin-treated mice, animals that received also PEA-um((r)) (3 or 10mg/kg) had significantly decreased weight loss, mortality, inflammation, lung damage at the histological level, and lung fibrosis at 7 and 21days. PEA-um((r)) (1mg/kg) did not significantly inhibit the inflammation response and lung fibrosis. This study demonstrates that PEA-um((r)) (3 and 10mg/kg) reduces the extent of lung inflammation in a mouse model of idiopathic pulmonary fibrosis. PMID- 27402189 TI - Full-Featured Search Algorithm for Negative Electron-Transfer Dissociation. AB - Negative electron-transfer dissociation (NETD) has emerged as a premier tool for peptide anion analysis, offering access to acidic post-translational modifications and regions of the proteome that are intractable with traditional positive-mode approaches. Whole-proteome scale characterization is now possible with NETD, but proper informatic tools are needed to capitalize on advances in instrumentation. Currently only one database search algorithm (OMSSA) can process NETD data. Here we implement NETD search capabilities into the Byonic platform to improve the sensitivity of negative-mode data analyses, and we benchmark these improvements using 90 min LC-MS/MS analyses of tryptic peptides from human embryonic stem cells. With this new algorithm for searching NETD data, we improved the number of successfully identified spectra by as much as 80% and identified 8665 unique peptides, 24 639 peptide spectral matches, and 1338 proteins in activated-ion NETD analyses, more than doubling identifications from previous negative-mode characterizations of the human proteome. Furthermore, we reanalyzed our recently published large-scale, multienzyme negative-mode yeast proteome data, improving peptide and peptide spectral match identifications and considerably increasing protein sequence coverage. In all, we show that new informatics tools, in combination with recent advances in data acquisition, can significantly improve proteome characterization in negative-mode approaches. PMID- 27402191 TI - Multidrug resistance-associated protein 4 (MRP4) controls ganciclovir intracellular accumulation and contributes to ganciclovir-induced neutropenia in renal transplant patients. AB - Ganciclovir (GCV) is the cornerstone of cytomegalovirus prevention and treatment in transplant patients. It is associated with problematic adverse hematological effects in this population of immunosuppressed patients, which may lead to dose reduction thus favoring resistance. GCV crosses the membranes of cells, is activated by phosphorylation, and then stops the replication of viral DNA. Its intracellular accumulation might favor host DNA polymerase inhibition, hence toxicity. Following this hypothesis, we investigated the association between a selected panel of membrane transporter polymorphisms and the evolution of neutrophil counts in n=174 renal transplant recipients. An independent population of n=96 renal transplants served as a replication and experiments using HEK293T transfected cells were performed to validate the clinical findings. In both cohorts, we found a variant in ABCC4 (rs11568658) associated with decreased neutrophil counts following valganciclovir (GCV prodrug) administration (exploratory cohort: beta+/-SD=-0.68+/-0.28, p=0.029; replication cohort: beta+/ SD=-0.84+/-0.29, p=0.0078). MRP4-expressing cells showed decreased GCV accumulation as compared to negative control cells (transfected with an empty vector) (-61%; p<0.0001). The efflux process was almost abolished in cells expressing MRP4 rs11568658 variant protein. Molecular dynamic simulations of GCV membrane crossing showed a preferred location of the drug just beneath the polar head group region, which supports its interaction with efflux transporters. PMID- 27402192 TI - Polyphenol-based nutraceuticals for the control of angiogenesis: Analysis of the critical issues for human use. AB - Angiogenesis, the formation of new blood-vessel, is crucial in the pathogenesis of several diseases, and thus represents a druggable target for the prevention and treatment of different disorders. It is nowadays well kwon how diet can control cancer development and progression, and how the use of certain diet components can prevent cancer development. Several studies, also from our lab, now indicate that natural plant products including nutraceuticals modulate tumor angiogenesis. In this review, it is reported how phytochemicals, comprising hydroxytyrosol, resveratrol, genistein, curcumin, and the green tea component epigallocatechin-3-gallate among the others, negatively regulate angiogenesis. A single plant-derived compound may affect both endothelial and tumor cells, with the common denominator of anti-inflammatory and radical scavenger activities. Beside these positive features, documented in cellular and animal models, a series of critical issues should be considered from a pharmacological point of view as: what is the best source of bioactive compounds: food and beverages, extracted phytocomplexes, isolated nutraceuticals or synthetic analogues? How is the bioavailability of the compounds of interest in relation to the above source? Is there any biological activity by circulating metabolic derivatives? What is the best formulation, administration route and posology? How safe are in humans? How strong and reliable are the clinical trials designed for their use alone or in combination with conventional chemotherapy? After a dissertation of these critical points, the conclusion can be drawn that novel and effective strategies should be optimized to improve their bioavailability and efficacy, considering their exploitation as chemopreventive and/or curative approaches. PMID- 27402193 TI - Improving Erythritol Production of Aureobasidium pullulans from Xylose by Mutagenesis and Medium Optimization. AB - The biotransformation of xylose, the second most abundant sugar, has been a hot topic in recent years. In this work, Aureobasidium pullulans CGMCC3.0837 was subjected to UV mutagenesis to improve its erythritol production from xylose. The erythritol production of the obtained mutant ER35 was 50.92 % (17.28 g/L) higher than that of the parent strain. Response surface methodology was applied to optimize the medium composition. Yeast extract, KH2PO4, and citric acid were the key factors influencing erythritol synthesis, and the optimal concentrations were 17.82, 0.76, and 6.60 g/L, respectively. Under the optimized conditions, 31.75 and 31.42 g/L erythritol were obtained in shake flasks and in a 5-L fermentor, respectively. ER35 also showed a good consuming ability on xylose mother liquor with a final erythritol production of 26.35 g/L. This report provided insights into the potential of A. pullulans for the production of erythritol using xylose as a carbon source. PMID- 27402194 TI - Multilayer Heterojunction Anodes for Saline Wastewater Treatment: Design Strategies and Reactive Species Generation Mechanisms. AB - Multilayer heterojunction SbSn/CoTi/Ir anodes, which consist of Ir0.7Ta0.3O2 bottom layers coated onto a titanium base, Co-TiO2 interlayers, and overcoated discrete Sb-SnO2 islands, were prepared by spray pyrolysis. The Ir0.7Ta0.3O2 bottom layer serves as an Ohmic contact to facilitate electron transfer from semiconductor layers to the Ti base. The Co-TiO2 interlayer and overcoated Sb SnO2 islands enhance the evolution of reactive chlorine. The surficial Sb-SnO2 islands also serve as the reactive sites for free radical generation. Experiments coupled with computational kinetic simulations show that while .OH and Cl. are initially produced on the SbSn/CoTi/Ir anode surface, the dominant radical formed in solution is the dichlorine radical anion, Cl2.(-). The steady-state concentration of reactive radicals is 10 orders of magnitude lower than that of reactive chlorine. The SbSn/CoTi/Ir anode was applied to electrochemically treat human wastewater. These test results show that COD and NH4(+) can be removed after 2 h of electrolysis with minimal energy consumption (370 kWh/kg COD and 383 kWh/kg NH4(+)). Although free radical species contribute to COD removal, anodes designed to enhance reactive chlorine production are more effective than those designed to enhance free radical production. PMID- 27402195 TI - Pro-inflammatory cytokines in cryptoglandular anal fistulas. AB - BACKGROUND: Sphincter-preserving procedures for the treatment of transsphincteric fistulas fail in at least one out of every three patients. It has been suggested that failure is due to ongoing disease in the remaining fistula tract. Cytokines play an important role in inflammation. At present, biologicals targeting cytokines are available. Therefore, detection and identification of cytokines in anal fistulas might have implications for future treatment modalities. The objective of the present study was to assess local production of a selected panel of cytokines in anal fistulas, including pro-inflammatory interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha). METHODS: Fistula tract tissue was obtained from 27 patients with a transsphincteric fistula of cryptoglandular origin who underwent flap repair, ligation of the intersphincteric fistula tract or a combination of both procedures. Patients with a rectovaginal fistula or a fistula due to Crohn's disease were excluded. Frozen tissue samples were sectioned and stained using advanced immuno-enzyme staining methods for detection of selected cytokines, IL-1beta, IL-8, IL-10, IL-12p40, IL-17A, IL-18, IL-36 and TNF-alpha. The presence and frequencies of cytokine-producing cells in samples were quantitated. RESULTS: The key finding was abundant expression of IL-1beta in 93 % of the anal fistulas. Frequencies of IL-1beta-producing cells were highest (>50 positive stained cells) in 7 % of the anal fistulas. Also, cytokines IL-8, IL-12p40 and TNF-alpha were present in respectively 70, 33 and 30 % of the anal fistulas. CONCLUSIONS: IL-1beta is expressed in the large majority of cryptoglandular anal fistulas, as well as several other pro-inflammatory cytokines. PMID- 27402196 TI - A mixed solvent system for preparation of spherically agglomerated crystals of ascorbic acid. AB - The objective of this research was to develop a novel solvent system to prepare spherically agglomerated crystals (SAC) of ascorbic acid with improved flowability for direct compression. A spherical agglomeration method was developed by selecting the mixed solvents (n-butyl and ethyl acetate) as a poor solvent and the process was further optimized by using triangular phase diagram and particle vision measurement. Physiochemical properties of SAC were characterized and compared with original drug crystals. It showed that amount of poor solvent, ratio of solvent mixture, and drug concentration are critical for preparation of SAC with desirable properties. The solid state of SAC was same as original crystals according to DSC, XRD, and FT-IR results. There was no significant difference in solubility and dissolution rate of drug between SAC and original crystals. The flowability and packability of SAC as well as the tensile strength and elastic recovery of tablets made from SAC were all significantly improved when compared with original crystals and tablets from crystals. It is concluded that the present method was suitable to prepare SAC of ascorbic acid for direct compression. PMID- 27402197 TI - Optically active multi-helical erythrocyte-like Ln(OH)CO3 (Ln = La, Ce, Pr and Sm). AB - Hierarchical erythrocyte-like Ln(OH)CO3 with nanosized chiral structure-induced circular dichroism responses were fabricated. The CD responses were observed not only in the UV region but also in the visible region, and are assigned to the electronic transitions from the valence band to the conduction band and the mixed coupling effect between the hierarchical left-handed-assembled Ln(OH)CO3 nanorods in the multi-helical RBC-like architecture. PMID- 27402198 TI - Iron distribution and histopathological study of the effects of deferoxamine and deferiprone in the kidneys of iron overloaded beta-thalassemic mice. AB - Renal glomerular and tubular dysfunctions have been reported with high prevalence in beta-thalassemia. Iron toxicity is implicated in the kidney damage, which may be reversed by iron chelation therapy. To mimic heavy iron overload and evaluate the efficacy of iron chelators in the patients, iron dextran (180mg iron/mouse) was intraperitoneally (i.p.) injected in heterozygous beta-globin knockout mice ((mubetath-3/+), BKO) and wild type mice (C57BL/6J, WT) over a period of 2 weeks, followed by daily i.p. injection of deferoxamine (DFO) or deferiprone (L1) for 1 week. In BKO mice, iron preferentially accumulated in the proximal tubule with a grading score of 0-1 and increased to grade 3 after iron loading. In contrast, iron mainly deposited in the glomerulus and interstitial space in iron overloaded WT mice. Increased levels of kidney lipid peroxidation, glomerular and medullar damage and fibrosis in iron overloaded mice were reversed by treatment with iron chelators. L1 showed higher efficacy than DFO in reduction of glomerular iron, which was supported by a significantly decreased the amount of glomerular damage. Notably, DFO and L1 demonstrated a distinct pattern of iron distribution in the proximal tubule of BKO mice. In conclusion, chelation therapy has beneficial effects in iron-overloaded kidneys. However, the defect of kidney iron metabolism in thalassemia may be a determining factor of the treatment outcome in individual patients. PMID- 27402199 TI - Aberrant cell cycle regulation in rat liver cells induced by post-initiation treatment with hepatocarcinogens/hepatocarcinogenic tumor promoters. AB - The present study aimed to determine the onset time of hepatocarcinogen/hepatocarcinogenic tumor promoter-specific cell proliferation, apoptosis and aberrant cell cycle regulation after post-initiation treatment. Six week-old rats were treated with the genotoxic hepatocarcinogen, carbadox (CRB), the marginally hepatocarcinogenic leucomalachite green (LMG), the tumor promoter, beta-naphthoflavone (BNF) or the non-carcinogenic hepatotoxicant, acetaminophen, for 2, 4 or 6 weeks during the post-initiation phase using a medium-term liver bioassay. Cell proliferation activity, expression of G2 to M phase- and spindle checkpoint-related molecules, and apoptosis were immunohistochemically analyzed at week 2 and 4, and tumor promotion activity was assessed at week 6. At week 2, hepatocarcinogen/tumor promoter-specific aberrant cell cycle regulation was not observed. At week 4, BNF and LMG increased cell proliferation together with hepatotoxicity, while CRB did not. Additionally, BNF and CRB reduced the number of cells expressing phosphorylated-histone H3 in both ubiquitin D (UBD)(+) cells and Ki-67(+) proliferating cells, suggesting development of spindle checkpoint dysfunction, regardless of cell proliferation activity. At week 6, examined hepatocarcinogens/tumor promoters increased preneoplastic hepatic foci expressing glutathione S-transferase placental form. These results suggest that some hepatocarcinogens/tumor promoters increase their toxicity after post-initiation treatment, causing regenerative cell proliferation. In contrast, some genotoxic hepatocarcinogens may disrupt the spindle checkpoint without facilitating cell proliferation at the early stage of tumor promotion. This suggests that facilitation of cell proliferation and disruption of spindle checkpoint function are induced by different mechanisms during hepatocarcinogenesis. Four weeks of post-initiation treatment may be sufficient to induce hepatocarcinogen/tumor promoter-specific cellular responses. PMID- 27402200 TI - Role of MRI for detecting micro cracks in teeth. AB - OBJECTIVES: To evaluate the limit of tooth crack width visualization by two MRI pulse sequences in comparison with CBCT. METHODS: Two extracted human teeth with known crack locations and dimensions, as determined by reference standard microCT, were selected for experimental imaging. Crack location/dimension and the presence of common dental restorative materials such as amalgam were typical of that found clinically. Experimental imaging consisted of conventional CBCT scans and MRI scans with two pulse sequences including Sweep Imaging with Fourier Transformation (SWIFT) and gradient echo (GRE). CBCT and MR images of extracted teeth were acquired using acquisition parameters identical to those used for in vivo imaging. Experimental and reference standard images were registered and the limit of tooth crack visualization was determined. RESULTS: Collected images indicate that SWIFT could demonstrate cracks with 20-um width, which is 10 times narrower than the imaging voxel size. Cracks of this size were not visible in GRE images, even with a short echo time of 2.75 ms. The CBCT images were distorted by artefacts owing to close location of metallic restorations. CONCLUSIONS: The successful visualization of cracks with the SWIFT MRI sequence compared with other clinical modalities suggests that SWIFT MRI can effectively detect microcracks in teeth and therefore may have potential to be a non-invasive method for the in vivo detection of cracks in human teeth. PMID- 27402202 TI - Clamping down on mismatches. AB - A sliding clamp complex may help correct DNA replication errors by keeping track of which DNA strand is new and which is the template. PMID- 27402201 TI - MutSalpha maintains the mismatch repair capability by inhibiting PCNA unloading. AB - Eukaryotic mismatch repair (MMR) utilizes single-strand breaks as signals to target the strand to be repaired. DNA-bound PCNA is also presumed to direct MMR. The MMR capability must be limited to a post-replicative temporal window during which the signals are available. However, both identity of the signal(s) involved in the retention of this temporal window and the mechanism that maintains the MMR capability after DNA synthesis remain unclear. Using Xenopus egg extracts, we discovered a mechanism that ensures long-term retention of the MMR capability. We show that DNA-bound PCNA induces strand-specific MMR in the absence of strand discontinuities. Strikingly, MutSalpha inhibited PCNA unloading through its PCNA interacting motif, thereby extending significantly the temporal window permissive to strand-specific MMR. Our data identify DNA-bound PCNA as the signal that enables strand discrimination after the disappearance of strand discontinuities, and uncover a novel role of MutSalpha in the retention of the post-replicative MMR capability. PMID- 27402203 TI - Population size vs. social connectedness - A gene-culture coevolutionary approach to cumulative cultural evolution. AB - It has long been debated if population size is a crucial determinant of the level of culture. While empirical results are mixed, recent theoretical studies suggest that social connectedness between people may be a more important factor than the size of the entire population. These models, however, do not take into account evolutionary responses of learning strategies determining the mode of transmission and innovation and are hence not suitable for predicting the long term implications of parameters of interest. In the present paper, to address this issue, we provide a gene-culture coevolution model, in which the microscopic learning process of each individual is explicitly described as a continuous-time stochastic process and time allocation to social and individual learning is allowed to evolve. We have found that social connectedness has a larger impact on the equilibrium level of culture than population size especially when connectedness is weak and population size is large. This result, combined with those of previous culture-only models, points to the importance of studying separate effects of population size and internal social structure to better understand spatiotemporal variation in the level of culture. PMID- 27402204 TI - Heterologous Immune Responses to Influenza Vaccine in Kidney Transplant Recipients. AB - Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. Despite this, influenza vaccine may have the added benefit of inducing a cross-reactive immune response to viral strains not found in the vaccine. This is termed "heterologous immunity" and has not been assessed previously in transplant patients. Pre- and postvaccination sera from kidney transplant recipients (n = 60) immunized with the 2012-2013 adjuvanted or nonadjuvanted influenza vaccine underwent testing by hemagglutination inhibition assay for strains not present in vaccine: A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2) and B/Brisbane/60/2008. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 80.0 to 136.1, p < 0.001; H3N2: 23.3 to 77.3, p < 0.001; B: 13.3 to 19.5, p < 0.001). Seroconversion rates were 16.7%, 41.7%, and 13.3%, respectively. No differences in heterologous response were seen in the adjuvanted versus nonadjuvanted groups. Patients were more likely to seroconvert for a cross-reactive antigen if they seroconverted for the specific vaccine antigen. Seroconversion to heterologous A/H3N2, for example, was 84.0% for homologous H3N2 seroconverters versus 11.4% for nonseroconverters (p < 0.001). This study provides novel evidence that transplant recipients are able to mount significant cross-protective responses to influenza vaccine that may be an additional, previously unknown benefit of immunization. PMID- 27402205 TI - Unilateral Clearance for Primary Hyperparathyroidism in Selected Patients with Multiple Endocrine Neoplasia Type 1. AB - BACKGROUND: Primary hyperparathyroidism is the most common manifestation of multiple endocrine neoplasia type 1 (MEN1). Guidelines advocate subtotal parathyroidectomy (STP) or total parathyroidectomy with autotransplantation due to high prevalence of multiglandular disease; however, both are associated with a significant risk of permanent hypoparathyroidism. More accurate imaging and use of intraoperative PTH levels may allow a less extensive initial parathyroidectomy (unilateral clearance, removing both parathyroids with cervical thymectomy) in selected MEN1 patients with primary hyperparathyroidism. METHODS: We performed a retrospective cohort study at a high-volume tertiary medical center including patients with MEN1 and primary hyperparathyroidism, who underwent STP or unilateral clearance as their initial surgery from 1995 to 2015. Unilateral clearance was offered to patients who had concordant sestamibi and ultrasound showing a single enlarged parathyroid gland. For both the groups, we compared rates of persistent/recurrent disease and permanent hypoparathyroidism. RESULTS: Eight patients had unilateral clearance and 16 had STP. Subtotal parathyroidectomy patients were younger (37 vs 52 years). One patient in each group had persistent disease. One (13 %) unilateral clearance and five (31 %) STP patients had recurrent hyperparathyroidism after a mean follow-up of 47 and 68 months (p = 0.62). No unilateral clearance patients and two of 16 SPT patients had permanent hypoparathyroidism (p = 0.54). CONCLUSIONS: Some MEN1 patients with primary hyperparathyroidism who have concordant localizing studies may be selected for unilateral clearance as an alternative to STP. For appropriately selected MEN1 patients, unilateral clearance can achieve similar results as STP and has no risk of permanent hypoparathyroidism, and may facilitate possible future reoperations. PMID- 27402206 TI - Fungal keratitis due to Schizophyllum commune: an emerging pathogenic fungus. AB - Fungal keratitis due to Schizophyllum commune is very rare. In this study, we report the clinical and microbiological profile of five patients with fungal keratitis due to S. commune. Direct microscopic examination of corneal scrapings from all five patients showed septate branching hyaline fungal filaments. Similarly, in all five patients Sabouraud dextrose agar (SDA) plates inoculated with corneal scrapings showed white, cottony colonies on the second day of incubation. Lactophenol cotton blue stained wet preparation of 7-day-old colonies on SDA revealed clamp connections and no spores. The fungus was identified by its characteristic clamp connections, fan-shaped bracket fruiting body with pinkish grey longitudinally split-radiating gills. The phenotypic identification of one of the five isolates further conformed by ITS sequencing. Treatment outcome was available for two of the five patients; in these two patients, the keratitis resolved with topical natamycin. PMID- 27402207 TI - Zebrafish connexin 79.8 (Gja8a): A lens connexin used as an electrical synapse in some neurons. AB - In the mammalian central nervous system, a remarkably small number of connexins is used in electrical synapses, with the majority formed from Cx36. A larger number has been detected in teleosts, with some seeming to serve restricted roles. Here, we report the discovery of a new connexin expressed in the zebrafish lens and a limited set of neurons. Zebrafish cx79.8 (gja8a), previously annotated incorrectly as cx50.5 based on a partial cDNA sequence, is a homologue of mammalian Cx50 (Gja8). We examined its expression through transgenic promoter reporter constructs, in situ hybridization, and immunolabeling, and examined regulation of coupling in transfected HeLa cells. cx79.8 was expressed most strongly in the lens, but expression was also found in several groups of neurons in the cerebellum and related areas at the midbrain-hindbrain boundary, in cone photoreceptors, and in neurons in the retinal inner nuclear and ganglion cell layers. Labeling in the retina with antibodies against two C-terminal epitopes revealed numerous small punctate spots in the inner plexiform layer and along the somata of cones. Abundant gap junctions were labeled in the outer 1/3 of the lens, but were absent from the center, suggesting that the epitopes or the entire protein was absent from the center. Cx79.8 tracer coupling was strongly regulated by phosphorylation, and was extremely low in control conditions in HeLa cells due to protein phosphatase 2A activity. These properties allow coupling to be strongly restricted in situ, a frequently observed property for electrical synapses. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 548-561, 2017. PMID- 27402209 TI - The TRPM7 interactome defines a cytoskeletal complex linked to neuroblastoma progression. AB - Neuroblastoma is the second-most common solid tumor in children and originates from poorly differentiated neural crest-derived progenitors. Although most advanced stage metastatic neuroblastoma patients initially respond to treatment, a therapy resistant pool of poorly differentiated cells frequently arises, leading to refractory disease. A lack of insight into the molecular mechanisms that underlie neuroblastoma progression hampers the development of effective new therapies for these patients. Normal neural crest development and maturation is guided by physical interactions between the cell and its surroundings, in addition to soluble factors such as growth factors. This mechanical crosstalk is mediated by actin-based adhesion structures and cell protrusions that probe the cellular environment to modulate migration, proliferation, survival and differentiation. Whereas such signals preserve cellular quiescence in non malignant cells, perturbed adhesion signaling promotes de-differentiation, uncontrolled cell proliferation, tissue invasion and therapy resistance. We previously reported that high expression levels of the channel-kinase TRPM7, a protein that maintains the progenitor state of embryonic neural crest cells, are closely associated with progenitor-like features of tumor cells, accompanied by extensive cytoskeletal reorganization and adhesion remodeling. To define mechanisms by which TRPM7 may contribute to neuroblastoma progression, we applied a proteomics approach to identify TRPM7 interacting proteins. We show that TRPM7 is part of a large complex of proteins, many of which function in cytoskeletal organization, cell protrusion formation and adhesion dynamics. Expression of a subset of these TRPM7 interacting proteins strongly correlates with neuroblastoma progression in independent neuroblastoma patient datasets. Thus, TRPM7 is part of a large cytoskeletal complex that may affect the malignant potential of tumor cells by regulating actomyosin dynamics and cell-matrix interactions. PMID- 27402211 TI - Reconstruction of neglected achilles tendon ruptures with gastrocnemius flaps: excellent results in long-term follow-up. AB - OBJECTIVE: Repair of the neglected achilles tendon ruptures can be challenging due to retraction of tendon stumps. Different repair and augmentation techniques were described. This study aims to investigate long-term results of neglected achilles tendon rupture repair with gastrocnemius flaps. PATIENTS AND METHODS: Between 1995 and 2005, 21 neglected achilles tendon rupture reconstructions were performed with using gastrocnemius fascial flaps. Mean age was 32.1 years. Mean period between rupture and operation was 8.4 weeks. Ankle range of motion, calf circumference, heel raise test, Visual Analog Scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) hindfoot and Foot and Ankle Disability Index (FADI) scores were checked. RESULTS: The average gap length was 6.4 cm. Mean follow-up was 145.3 months. Median dorsiflexion/plantar flexion values for operated and uneffected sides were 18 degrees /30 degrees and 19 degrees /30 degrees , respectively. The mean values for AOFAS and FADI scores were 98.5 points and 98.9 %, respectively. VAS score was 0 point for all patients. With the numbers available, no significant difference could be detected in terms of ankle range of motion, calf circumference measures and dynamometric analysis. Mean time for return to daily activities was 11.1 (8-16) weeks after surgery. Prerupture activity level was achieved 14.1 months postoperatively. All patients were able to perform heel raise test. CONCLUSION: Repair of neglected achilles tendon ruptures with gastrocnemius flaps has satisfactory long-term results. PMID- 27402210 TI - A comparative analysis of analgesic efficacy of ultrasound and shock wave therapy in the treatment of patients with inflammation of the attachment of the plantar fascia in the course of calcaneal spurs. AB - INTRODUCTION: Troublesome heel spur is a nuisance condition that affects people of all ages. Treatment of patients with heel spur is a difficult and lengthy process requiring patience from both the patient and the therapist. Sometimes, the only and ultimate method of treatment is surgery, although spurs tend to recur. The aim of the study is a comparative analysis of the analgesic efficacy of ultrasound and shock wave therapy in patients with heel spur. The cause of pain in the course of calcaneal spur is inflammation of the attachment of the plantar fascia, which plays an important role in the process of walking and is seriously strained during different types of movement. Treatment of patients is a difficult and lengthy process. MATERIALS AND METHODS: The study was conducted on a group of 47 patients of both sexes, aged 38-60 years (mean 51.3) with a plantar calcaneal spur confirmed by X-ray images. Patients were randomly assigned into two groups using a simple randomization: Group 1-ultrasound therapy group (a series of ten treatments) and Group 2-the radial shock wave group (series of four treatments). In all patients, pain intensity was assessed three times: before therapy, after the first and second weeks of treatment. A version of Laitinen's pain assessment questionnaire and the Huskisson visual analogue scale (VAS) were used. Of the group of studied respondents, 47 patients of both sexes and aged 38 60 years (mean age 51.3) with a heel spur (confirmed on X-rays), who had pain for at least a month, were randomly included in the study. The patients were classified into: Group 1-US therapeutic group (a series of ten treatments) and Group 2-with RSWT (a series of five treatments). Pain intensity was assessed three times: before the treatment, after the first and second week of the treatment with the application of the VAS and the Leitinen Pain Questionnaire. RESULTS: However, a decrease in pain sensation was reported in all test intervals, and its largest decrease occurred in both groups within 1 week of beginning treatment. More dynamic change in this period was recorded in Group 1. CONCLUSION: The conclusion is that while ultrasound and shock wave therapy show significant analgesic efficacy in patients with heel spur, fewer shock wave therapy sessions are needed than ultrasound sessions for effective relief, suggesting that the shock wave therapy has greater analgesic efficacy. A similar analgesic effect was achieved with the administration of a smaller number of shock wave treatments and a full series of ultrasound treatments. PMID- 27402208 TI - A new front in cell invasion: The invadopodial membrane. AB - Invadopodia are F-actin-rich membrane protrusions that breach basement membrane barriers during cell invasion. Since their discovery more than 30 years ago, invadopodia have been extensively investigated in cancer cells in vitro, where great advances in understanding their composition, formation, cytoskeletal regulation, and control of the matrix metalloproteinase MT1-MMP trafficking have been made. In contrast, few studies examining invadopodia have been conducted in vivo, leaving their physiological regulation unclear. Recent live-cell imaging and gene perturbation studies in C. elegans have revealed that invadopodia are formed with a unique invadopodial membrane, defined by its specialized lipid and associated protein composition, which is rapidly recycled through the endolysosome. Here, we provide evidence that the invadopodial membrane is conserved and discuss its possible functions in traversing basement membrane barriers. Discovery and examination of the invadopodial membrane has important implications in understanding the regulation, assembly, and function of invadopodia in both normal and disease settings. PMID- 27402212 TI - The incidence of deep vein thrombosis (DVT) during hip arthroscopic surgery. AB - INTRODUCTION: The use of hip arthroscopy has been widely increasing. Although deep vein thrombosis (DVT) is thought to be a serious complication of orthopaedic surgery, there were few reports discussing DVT related to hip arthroscopic surgery. This study aimed to investigate the incidence and risk factors of DVT related to hip arthroscopic surgery. MATERIALS AND METHODS: This retrospective study included 72 patients. Clinical diagnosis of DVT was confirmed through ultrasonography performed preoperatively and 3 days postoperatively. Additionally, D-dimer levels were measured preoperatively and on postoperative days 1, 3, and 7. Age, body mass index, operation time, procedure type, and D dimer levels were statistically compared between the two groups (identified DVT vs. no identified DVT). RESULTS: Five patients (6.94 %) were diagnosed with DVT clinically, although all cases were asymptomatic. The mean age of the patients with identified DVT was 62.0 +/- 6.1 years; significantly higher than the mean age of the patients without DVT (45.1 +/- 1.7 years; P = 0.0188). CONCLUSION: The incidence of DVT during hip arthroscopy, investigated by ultrasound, was 6.94 %. From our results, we recommend screening for and treatment of asymptomatic DVT, especially in older patients, during hip arthroscopic surgery. PMID- 27402213 TI - Injectable autologous chondrocyte transplantation for full thickness acetabular cartilage defects: early clinical results. AB - INTRODUCTION: Acetabular cartilage lesions are frequently seen in young patients with hip pain and have been identified as an important prognostic factor. New therapies have complemented abrasion and microfracture procedures. The aim of the study is to evaluate the early outcome of patients with arthroscopic injectable autologous chondrocyte transplantations (ACT) for full thickness acetabular cartilage defects. METHODS: A two-step procedure ACT was performed in patients with full thickness acetabular cartilage defects measuring >=2 cm(2). The patients were closely followed with clinical examination, pre- and postoperative scores until the latest available follow-up of 3, 6, 12, and 24 months. RESULTS: 20 consecutive cases (4 female, 16 male, mean age 33 years) were included. No patients were lost at final follow-up. The average defect size was 5.05 (range 2 6) cm(2). The average follow-up was 12.05 (range 6-24) months. Three months postoperatively the preoperative scores improved significantly from a mean mHHS of 63-81 points (p = 0.009), iHOT33 of 44-66 % (p = 0.028) and subjective hip assessment (Subjective Hip Value, SHV) of 60-87 % (p = 0.007). After 12 months the results improved significantly to a mean mHHS of 93 points (p = 0.017), an iHOT33 of 79 % (p = 0.007) and an SHV of 82 % (p = 0.048) compared with the preoperative scores. DISCUSSION: The injectable matrix associated ACT is a reliable procedure, yielding promising early results with a significant increase of all scores evaluated in patients with full thickness acetabular cartilage defects. PMID- 27402214 TI - Accuracy of pedicle screw insertion in the thoracic and lumbar spine: a comparative study between percutaneous screw insertion and conventional open technique. AB - INTRODUCTION: In the last decade, posterior instrumented fusion using percutaneous pedicle screws (PPSs) had been growing in popularity, and its safety and good clinical results have been reported. However, there have been few previous reports of the accuracy of PPS placement compared with that of conventional open screw insertion in an institution. This study aimed to evaluate the accuracy of PPS placement compared with that of conventional open technique. MATERIALS AND METHODS: One hundred patients were treated with posterior instrumented fusion of the thoracic and lumbar spine from April 2008 to July 2013. Four cases of revised instrumentation surgery were excluded. In this study, the pedicle screws inserted below Th7 were investigated, therefore, a total of 455 screws were enrolled. Two hundred and ninety-three pedicle screws were conventional open-inserted screws (O-group) and 162 screws were PPSs (P-group). We conducted a comparative study about the accuracy of placement between the two groups. Postoperative computed tomography scans were carried out to all patients, and the pedicle screw position was assessed according to a scoring system described by Zdichavsky et al. (Eur J Trauma 30:241-247, 2004; Eur J Trauma 30:234-240, 2004) and a classification described by Wiesner et al. (Spine 24:1599 1603, 1999). RESULTS: Based on Zdichavsky's scoring system, the number of grade Ia screws was 283 (96.6 %) in the O-group and 153 (94.4 %) in the P-group, whereas 5 screws (1.7 %) in the O-group and one screw (0.6 %) in the P-group were grade IIIa/IIIb. Meanwhile, the pedicle wall penetrations based on Wiesner classification were demonstrated in 20 screws (6.8 %) in the O-group, and 12 screws (7.4 %) in the P-group. No neurologic complications were observed and no screws had to be replaced in both groups. CONCLUSIONS: The PPSs could be ideally inserted without complications. There were no statistically significant differences about the accuracy between the conventional open insertion and PPS placement. PMID- 27402215 TI - Abusive head trauma: an epidemiological and cost analysis. AB - OBJECTIVE Research on pediatric abusive head trauma (AHT) has largely focused on clinical presentation and management. The authors sought to review a single institution experience from a public health perspective to gain a better understanding of the local population affected, determine overall incidence and seasonal trends, and provide details on the initial hospitalization, including extent of injuries, neurosurgical interventions, and hospital charges. METHODS All cases of AHT involving patients who presented to Le Bonheur Children's Hospital (LBCH) from 2009 through 2014 were identified. AHT was defined as skull fracture or intracranial hemorrhage in a child under the age of 5 years with a suspicious mechanism or evidence of other intentional injuries, such as retinal hemorrhages, old or new fractures, or soft-tissue bruising. Injuries were categorized as Grade I (skull fracture only), Grade II (intracranial hemorrhage or edema not requiring surgical intervention), or Grade III (intracranial hemorrhage requiring intervention or death due to brain injury). RESULTS Two hundred thirteen AHT cases were identified. The demographics of the study population are similar to those reported in the literature: the majority of the patients involved were 6 months of age or younger (55%), male (61%), African American (47%), and publicly insured (82%). One hundred one neurosurgical procedures were performed in 58 children, with the most common being bur hole placement for treatment of subdural collections (25%) and decompressive hemicraniectomy (22%). The annual incidence rate rose from 2009 (19.6 cases per 100,000 in the population under 5 years of age) to 2014 (47.4 cases per 100,000) and showed seasonal peaks in January, July, and October (6-year average single month incidence, respectively, 24.7, 21.7, and 24.7 per 100,000). The total hospital charges were $13,014,584, with a median cost of $27,939. Treatment costs for children who required surgical intervention (i.e., those with Grade III) were up to 10 times those of children with less severe injuries. CONCLUSIONS In the authors' local population, victims of AHT are overwhelmingly infants, are more often male than female, and are disproportionately from lower socioeconomic ranks. The incidence is increasing and initial hospitalization charges are substantial and variable. The authors introduce a simple 3-tiered injury classification scheme that adequately stratifies length of hospital stay and cost. PMID- 27402216 TI - c-Met expression and MET amplification in malignant pleural mesothelioma. AB - c-Met is a receptor tyrosine kinase shown to be overexpressed in malignant pleural mesothelioma (MPM). Whereas MET mutations have been identified in 3%-16% of MPMs, MET amplification has recently been reported in a single epithelioid MPM. We studied c-Met expression and MET amplification in a large MPM cohort and correlated results with morphologic and clinical features. We report the first case of MET amplification in sarcomatoid MPM. MPMs from surgical pathology files (1989-2014) were reviewed. c-Met immunohistochemistry was performed. Staining intensity and distribution were multiplied (H-score). Staining localization (cytoplasmic and/or membranous) was noted. Fluorescence in situ hybridization was performed using probes for MET and centromere 7. One hundred forty-nine patients (median age, 68.0years; interquartile range, 61-75) had epithelioid (n=97), biphasic (n=18), or sarcomatoid (n=34) MPM. Median follow-up was 10.1months (range, 0.1-222.5). One hundred thirty patients died of disease; 2 were alive with disease. c-Met was expressed in 147 MPMs. c-Met staining intensity, distribution, and H-score differed among the histologic subtypes (P=.015; P=.0001, and P=.0005, respectively), but none were predictive of survival. Epithelioid subtype had greater c-Met expression. MET amplification was identified in 1 sarcomatoid MPM and MET duplication in 1 epithelioid MPM; both had poor outcomes. Chromosome 7 aneusomy was observed in 54 of 144 (37.5%) MPMs and associated with decreased overall survival in sarcomatoid MPMs (hazard ratio=2.81; 95% confidence interval, 1.21-6.51; P=.01). In conclusion, c-Met is expressed in MPM, with significant differences in expression among histologic subtypes. MET amplification is a rare event in MPM, making it an unlikely common pathogenesis for c-Met expression. PMID- 27402217 TI - Cutaneous hidradenoma: a study of 21 neoplasms revealing neither correlation between the cellular composition and CRTC1-MAML2 fusions nor presence of CRTC3 MAML2 fusions. AB - Twenty-one hidradenomas from 20 patients (13 female, 7 male) ranging in age from 18 to 87years (mean, 57.75years; median, 60years) were studied for CRTC1-MAML2 and CRTC3-MAML2 fusions to find out whether there is a correlation between the particular cell type (polyhedral eosinophilic, clear, mucinous, epidermoid, and oncocytic) and presence the above alterations. CRTC1-MAML2 fusions were detected in 10 of the 21 neoplasms (47.6%). Fluorescence in situ hybridization for MAML2 break apart was analyzable in 13 specimens and in all these specimens was positive, including 4 tumors with no demonstrable CRTC1-MAML2 fusion. In none of the cases was a CRTC3-MAML2 fusion detected. No obvious correlation between the cellular composition and presence of t(11,19) translocation was found. PMID- 27402218 TI - Clinicopathologic and radiologic features of extraskeletal myxoid chondrosarcoma: a retrospective study of 40 Chinese cases with literature review. AB - The aim of this study is to describe the clinicopathologic and radiologic features of 40 cases of extraskeletal myxoid chondrosarcoma (EMC) from China. There were 25 males and 15 females (sex ratio, 1.7:1). Apart from an adolescent, all patients were adults with a median age of 49years. Twenty-four tumors (60%) occurred in the lower limb and limb girdles, especially the thigh, followed by the upper limb and limb girdles (20%) and trunk (10%). Other less commonly involved locations included the head and neck, sacrococcygeal region, and perineum. Tumors ranged in size from 1.5 to 19cm (mean, 7cm). By radiology, they appeared as hypoattenuated or isoattenuated masses on computed tomography with hyperintense signal on T2-weighted magnetic resonance imaging. Intralesional hypointense septa were present in most cases. Of the 40 tumors, 30 belonged to the classic subtype, whereas 9 cases were cellular, and 1 case had a rhabdoid phenotype. Tumor cells showed variable expression of synaptophysin (36%), S-100 protein (29%), epithelial membrane antigen (11%), and neuron-specific enolase (7%). Ki-67 index was remarkably higher in the cellular variant (mean, 30%). EWSR1-related rearrangement was detected in 12 of 14 cases tested by fluorescence in situ hybridization using break-apart probes. The overall 5- and 7-year survival was 71% and 60%, respectively. Awareness of the imaging features may help pathologists in the diagnosis of EMC. Fluorescence in situ hybridization also serves as a useful diagnostic tool for EMC, especially in the distinction from its mimics. PMID- 27402219 TI - Follicular dendritic cell sarcoma: clinicopathologic study of 15 cases with emphasis on novel expression of MDM2, somatostatin receptor 2A, and PD-L1. AB - Follicular dendritic cell sarcoma (FDCS) is a rare low-grade neoplasm with the phenotype of FDC cells. This rare sarcoma has been well known for being mistaken for a variety of neoplasms (mainly meningioma), particularly at extranodal sites. Diagnosis of FDCS mainly relies on characteristic histologic appearance supplemented by immunohistochemistry and electron microscopy. In this study, we reviewed 15 FDCSs retrieved from our consultation files and stained them for newly reported or novel markers (PD-L1, Rb1, MDM2, and somatostatin receptor 2A [SSTR2A]) in addition to conventional FDC markers. Patients were 7 men and 7 women (1 unspecified) with a mean age of 47 years (20-75 years). The tumor site was lymph nodes (6) or spleen (2), both (1) and extranodal sites of head and neck (4) or abdominal cavity (2). Treatment was variable combinations of surgery and aggressive chemotherapy/radiotherapy. Four of 8 patients with follow-up died of disease within 1 to 10 years. All tumors expressed at least 1 FDC marker: CD21 (8/13), CD23 (2/13), CD35 (8/12), CNA.42 (13/14), Clusterin (8/13), Fascin (15/15) and D2-40/podoplanin (7/14). Epstein-Barr virus (EBER-1/2 in situ hybridization) was performed successfully in 10 conventional variants; all were negative. Five of 14 cases (36%) stained strongly for SSTR2A with a distinctive membranous pattern. Residual lymphoid follicles surrounding some of the tumors stained similarly for SSTR2A. Seven (54%) of 13 assessable cases showed moderate to strong membranous staining for PD-L1 in greater than 5% of the neoplastic cells. The Rb1 antigen was lost in 4 (28%) of 14 cases. MDM2 stained less than 5% to 20% of the tumor cells in 5 (36%) of 14 cases; 2 of them showed amplification by fluorescence in situ hybridization (FISH). CDK4 was negative except for weak staining in 1 of 14 cases. This study adds to the existing few clinicopathologic series on FDCS and represents the first study to show MDM2 amplification in this entity. Our results regarding frequent SSTR2A expression in FDCS are novel and might be of potential diagnostic and therapeutic relevance. SSTR2A expression in FDCS represents a further confusing factor when thinking of meningioma which uniformly expresses this receptor. FDCS occurring within the retroperitoneum and/or the abdominal cavity may closely mimic dedifferentiated liposarcoma, particularly if MDM2 positive and/or amplified and should thus be carefully assessed for expression of FDC markers. PMID- 27402221 TI - A single center's approach to discriminating donor versus host origin of renal neoplasia in the allograft kidney. AB - Renal cell carcinoma (RCC) in the allograft of kidney transplant recipient (KTR) patients is rare and may represent a de novo process arising from the transplanted organ or metastasis from a clinically undetectable host primary. Determination of host versus donor origin is important for staging and management. We report our experience utilizing Penta-C (PC) and Penta-D (PD) short-tandem repeat (STR) microsatellite analysis to discriminate between host and donor origin of RCC identified in renal allografts. We identified 5 KTR patients with RCC in the allograft kidney. The PC and PD microsatellite analysis was applied to tumor, host, and donor formalin-fixed, paraffin-embedded tissue sections and/or fresh blood leukocytes to identify the origin of the neoplastic cells. The PC and PD microsatellite alleles were robustly amplified in all samples. Each case showed one or more informative alleles indicating that the neoplastic cells originate from donor tissue. Allele frequency data indicate that by using both PC and PD markers, we will be able to discriminate between host and donor cell of origin in over 99% of cases. The PC and PD microsatellite analysis is a convenient, robust, and efficient strategy to determine donor versus host origin or RCC in transplant kidney specimens. PMID- 27402220 TI - Utility of a standardized protocol for submitting clinically suspected endometrial polyps to the pathology laboratory. AB - The purpose of the study is to assess whether a protocol for submitting clinically suspected endometrial polyps will improve the detection rate of polyps and evaluation of the background endometrium. A retrospective review from 1999 to 2015 was performed. Cases were divided into (1) polyps and curettings placed in 2 containers (separate, n=61) and (2) polyps and curettings placed in 1 container (combined, n=80). Polyps were identified in 100% of cases in the separate compared with 95% in the combined group (P=.62). The background endometrium was evaluable in 79% of cases in the combined compared to 90% in the separate group (P=.07). The frequency of hyperplasia without atypia, atypical hyperplasia, and carcinoma was 4.4%, 3.6%, and 1.5%, respectively. In conclusion, the enhanced rate of polyp detection and evaluation of the background endometrium in the separate group is minimal. This supports the recommendation of submitting endometrial polyps and curettings combined in 1 container. PMID- 27402222 TI - Is the routine microscopic examination of proximal and distal resection margins in colorectal cancer surgery justified? AB - Microscopic examination of the proximal and distal resection margins is part of the routine pathologic evaluation of colorectal surgical specimens removed for adenocarcinoma. Anastomotic donuts are frequently received and microscopically examined. We examined 594 specimens received over a period of 10 years and found only 3 cases of definitive direct involvement of a longitudinal margin by carcinoma. All 3 cases also showed tumor at the margin grossly. One case of margin involvement by adenocarcinoma was found in which the tumor was grossly 1.7 cm away; however, this finding was likely a tumor deposit, as the patient had diffuse metastatic disease. All 242 anastomotic donuts examined were free of carcinoma. Our study suggests that the proximal and distal margins of colorectal cancer specimens need not be examined microscopically in order to accurately assess margin status in cases where the tumor is at least 2 cm away from the margin of resection. Also, in cases in which anastomotic donuts are included with the case, these should be considered the true margins of resection and may be microscopically examined in place of the bowel specimen margins when margin examination is needed. Anastomotic donuts need not be examined if the tumor is more than 2 cm away from the margin. An exception to this rule would be cases of rectal adenocarcinoma where neoadjuvant therapy is given prior to surgery. In these cases, mucosal evidence of malignancy may be absent and microscopic examination of the margins is the only way to assure complete excision. PMID- 27402223 TI - Peripheral nerve sheath tumors arising in salivary glands: A clinicopathologic study. AB - Primary salivary gland peripheral nerve sheath tumors (PNST) are uncommon. This study is a retrospective, clinicopathologic review of 9 cases of PNST (5 neurofibromas, 3 schwannomas and 1 malignant peripheral nerve sheath tumor (MPNST)) arising from the salivary glands, encountered between 1990 and 2015. All patients with neurofibromas were male (ages 1-62 years) and had a single parotid lesion of which 2 were diffuse, 2 plexiform and one mixed diffuse/plexiform. Four had a history of neurofibromatosis I. Four of 5 presented with symptoms related to mass effect including facial swelling, facial drooping, and dysphagia. All underwent de-bulking surgery and recurred due to continued growth. Of the 3 patients with schwannomas, 1 was male and 2 were female (ages 19, 44 and 56 years). One tumor each arose in the sublingual, submandibular, and parotid glands. Two of 3 presented with soreness and swelling local to the affected gland, especially while chewing. There was no recurrence of these tumors after resection. An MPNST in a male presented as a tender mass in the patient's left parotid; the tumor was resected. There was no evidence of tumor elsewhere in the body. The tumor did not recur in 12 years of follow-up. The most common tumor type in the current series was neurofibroma; most arose in the background of neurofibromatosis type I and all of which recurred after initial subtotal resection. Most PNST arose in the parotid gland. PMID- 27402224 TI - Diagnostic and prognostic significance of receptor-binding cancer antigen expressed on SiSo cells in lung-cancer-associated pleural effusion. AB - OBJECTIVES: This study aimed to evaluate the diagnostic and prognostic value of pleural effusion levels of soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) in lung cancer patients with malignant pleural effusion (MPE). METHODS: Pleural effusion samples were collected from 78 patients with MPE, and from 48 patients with benign pleural effusion (BPE). Pleural effusion sRCAS1 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: MPE has significantly higher sRCAS1 levels than that of BPE (P < .01). With a cutoff value of 18.7 U/mL, sRCAS1 showed a good diagnostic performance for MPE. Univariate and multivariate analysis indicated that elevated sRCAS1 levels were an independent predictor of overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves further confirmed that patients with high sRCAS1 have shorter DFS and OS (P = .026 and P = .032, respectively). CONCLUSION: In conclusion, measurement of sRCAS1 might be a useful diagnostic and prognostic marker for MPE. PMID- 27402225 TI - Glutamate-Like Neurons in the Turtle Brain. AB - Glutamate acts as the excitatory neurotransmitter in the brain and is mediated largely by the vesicular glutamate transporters (VGLUTs). The objective of the study was to determine the distribution of VGLUT2 mRNA in the turtle brain by in situ hybridization. Intense expression was observed in the olfactory bulb, cerebral cortex, nucleus dorsomedialis thalami, nucleus dorsolateralis thalami, dorsal lateral geniculate nucleus, nucleus reuniens and nucleus periventricularis hypothalami. Moderate expression was noticed in the nucleus rotundus, area lateralis hypothalami, reticular nucleus, cerebellar nucleus and nucleus cochlearis. In conclusion, this study reveals many glutamatergic neurons in the turtle brain. PMID- 27402226 TI - T Cells Going Innate. AB - Natural killer (NK) cell receptors (NKRs) play a crucial role in the homeostasis of antigen-experienced T cells. Indeed, prolonged antigen stimulation may induce changes in the receptor repertoire of T cells to a profile that features NKRs. Chronic antigen exposure, at the same time, has been shown to trigger the loss of costimulatory CD28 molecules with recently reported intensified antigen thresholds of antigen-experienced CD8(+) T cells. In transplantation, NKRs have been shown to assist allograft rejection in a CD28-independent fashion. We discuss here a role for CD28-negative T cells that have acquired the competency of the NKR machinery, potentially promoting allorecognition either through T cell receptor (TCR) crossreactivity or independently from TCR recognition. Collectively, NKRs can bring about innate-like T cells by providing alternative costimulatory pathways that gain relevance in chronic inflammation, potentially leading to resistance to CD28-targeting immunosuppressants. PMID- 27402228 TI - Spinal Subdural Abscess Following Laminectomy for Symptomatic Stenosis: A Report of 2 Cases and Review of the Literature. AB - BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess. PMID- 27402227 TI - Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion. AB - Membrane fusion is essential for eukaryotic life, requiring SNARE proteins to zipper up in an alpha-helical bundle to pull two membranes together. Here, we show that vesicle fusion can be suppressed by phosphorylation of core conserved residues inside the SNARE domain. We took a proteomics approach using a PKCB knockout mast cell model and found that the key mast cell secretory protein VAMP8 becomes phosphorylated by PKC at multiple residues in the SNARE domain. Our data suggest that VAMP8 phosphorylation reduces vesicle fusion in vitro and suppresses secretion in living cells, allowing vesicles to dock but preventing fusion with the plasma membrane. Markedly, we show that the phosphorylation motif is absent in all eukaryotic neuronal VAMPs, but present in all other VAMPs. Thus, phosphorylation of SNARE domains is a general mechanism to restrict how much cells secrete, opening the door for new therapeutic strategies for suppression of secretion. PMID- 27402230 TI - Atrial Fibrillation Patients Treated With Long-Term Warfarin Anticoagulation Have Higher Rates of All Dementia Types Compared With Patients Receiving Long-Term Warfarin for Other Indications. AB - BACKGROUND: The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long-term anticoagulation exposure. METHODS AND RESULTS: A total of 10 537 patients anticoagulated with warfarin (target INR 2-3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long-term risk of dementia remained significant in AF patients compared with matched non-AF patients (total dementia: hazard ratio [HR]=2.42 [1.85-3.18], P<0.0001; Alzheimer: HR=2.04 [1.40 2.98], P<0.0001; senile: HR=2.46 [1.58-3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26-50% versus >75%: HR=2.51, P=0.005) and non-AF groups (<=25% versus >75%: HR=3.92, P<0.0001). CONCLUSIONS: The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients. PMID- 27402229 TI - Automated Extracellular Volume Fraction Mapping Provides Insights Into the Pathophysiology of Left Ventricular Remodeling Post-Reperfused ST-Elevation Myocardial Infarction. AB - BACKGROUND: Whether the remote myocardium of reperfused ST-segment elevation myocardial infarction (STEMI) patients plays a part in adverse left ventricular (LV) remodeling remains unclear. We aimed to use automated extracellular volume fraction (ECV) mapping to investigate whether changes in the ECV of the remote (ECVR emote) and infarcted myocardium (ECVI nfarct) impacted LV remodeling. METHODS AND RESULTS: Forty-eight of 50 prospectively recruited reperfused STEMI patients completed a cardiovascular magnetic resonance at 4+/-2 days and 40 had a follow-up scan at 5+/-2 months. Twenty healthy volunteers served as controls. Mean segmental values for native T1, T2, and ECV were obtained. Adverse LV remodeling was defined as >=20% increase in LV end-diastolic volume. ECVR emote was higher on the acute scan when compared to control (27.9+/-2.1% vs 26.4+/ 2.1%; P=0.01). Eight patients developed adverse LV remodeling and had higher ECVR emote acutely (29.5+/-1.4% vs 27.4+/-2.0%; P=0.01) and remained higher at follow up (28.6+/-1.5% vs 26.6+/-2.1%; P=0.02) compared to those without. Patients with a higher ECVR emote and a lower myocardial salvage index (MSI) acutely were significantly associated with adverse LV remodeling, independent of T1Remote, T1Core and microvascular obstruction, whereas a higher ECVI nfarct was significantly associated with worse wall motion recovery. CONCLUSIONS: ECVR emote was increased acutely in reperfused STEMI patients. Those with adverse LV remodeling had higher ECVR emote acutely, and this remained higher at follow-up than those without adverse LV remodeling. A higher ECVR emote and a lower MSI acutely were significantly associated with adverse LV remodeling whereas segments with higher ECVI nfarct were less likely to recover wall motion. PMID- 27402231 TI - Catheter Ablation as a Treatment for Vasovagal Syncope: Long-Term Outcome of Endocardial Autonomic Modification of the Left Atrium. AB - BACKGROUND: Autonomic modification through catheter ablation of ganglionated plexi (GPs) in the left atrium has been reported previously as a treatment for vasovagal syncope. This study aimed to observe the long-term outcome in a larger cohort. METHODS AND RESULTS: A total of 57 consecutive patients (aged 43.2+/-13.4 years; 35 women) with refractory vasovagal syncope were enrolled, and high frequency stimulation and anatomically guided GP ablation were performed in 10 and 47 cases, respectively. A total of 127 GP sites with positive vagal response were successfully elicited and ablated, including 52 left superior, 19 left lateral, 18 left inferior, 27 right anterior, and 11 right inferior GPs. During follow-up of 36.4+/-22.2 months (range 12-102 months), 52 patients (91.2%) remained free from syncope. Prodromes recurred in 16 patients. No statistical differences were found between the high-frequency stimulation and anatomically guided ablation groups in either freedom from syncope (100% versus 89.4%, P=0.348) or recurrent prodromes (50% versus 76.6%, P=0.167). The deceleration capacity, heart rate, and heart rate variability measurements demonstrated a reduced vagal tone lasting for at least 12 months after the procedure, with improved tolerance of repeated head-up tilt testing. No complications were observed except for transient sinus tachycardia that occurred in 1 patient. CONCLUSIONS: Left atrial GP ablation showed excellent long-term clinical outcomes and might be considered as a therapeutic option for patients with symptomatic vasovagal syncope. PMID- 27402232 TI - Advanced Left Atrial Remodeling and Appendage Contractile Dysfunction in Women Than in Men Among the Patients With Atrial Fibrillation: Potential Mechanism for Stroke. AB - BACKGROUND: The risk of stroke imposed by atrial fibrillation (AF) is significantly greater in women than men; however, the mechanism remains elusive. We hypothesized that left atrial (LA) remodeling and poor contractile function of LA appendage (LAA) would be more predominant in women than men among AF patients. METHODS AND RESULTS: A total of 579 AF patients (216 women vs age-, AF type-, and incidences of heart failure, hypertension, diabetes mellitus, stroke or transient ischemic attack, and vascular disease-matched 363 men, 61.3+/-10.2 years old, 70.1% paroxysmal AF) who underwent AF catheter ablation were included. Sex differences in LA volume index (LAVI) and LAA emptying flow velocity (FV) were analyzed in risk factor 0, 1, and >=2 groups, according to their CHA2DS2-VASc scores beyond sex category. LAA-FV was more significantly reduced in women with risk factor >=2 than in men of the same risk group (P=0.022). Women showed greater LAVI than their male counterparts in the risk factor >=2 group (P<0.001). The majority of female patients with a history of stroke had a large LAVI and low LAA-FV (P<0.001); however, no such distribution was observed in men (P=0.596). LA volume index (odds ratio [OR], 1.038; 95% CI, 1.003-1.075, P=0.035) or LAA-FV (OR, 0.976; 95% CI, 0.952-0.999; P=0.047) was significantly associated with a history of stroke in women. CONCLUSIONS: More-extensive LA remodeling and deterioration in LAA function were noted in women than in men with high calculated risk of stroke in AF. PMID- 27402233 TI - Time Dependence of the Effect of Right Ventricular Dysfunction on Clinical Outcomes After Myocardial Infarction: Role of Pulmonary Hypertension. AB - BACKGROUND: The clinical importance of right ventricular (RV) function in acute myocardial infarction is well recognized, but the impact of concomitant pulmonary hypertension (PH) has not been studied. METHODS AND RESULTS: We studied 1044 patients with acute myocardial infarction. Patients were classified into 4 groups according to the presence or absence of RV dysfunction and PH, defined as pulmonary artery systolic pressure >35 mm Hg: normal right ventricle without PH (n=509), normal right ventricle and PH (n=373), RV dysfunction without PH (n=64), and RV dysfunction and PH (n=98). A landmark analysis of early (admission to 30 days) and late (31 days to 8 years) mortality and readmission for heart failure was performed. In the first 30 days, RV dysfunction without PH was associated with a high mortality risk (adjusted hazard ratio 5.56, 95% CI 2.05-15.09, P<0.0001 compared with normal RV and no PH). In contrast, after 30 days, mortality rates among patients with RV dysfunction were increased only when PH was also present. Compared with patients having neither RV dysfunction nor PH, the adjusted hazard ratio for mortality was 1.44 (95% CI 0.68-3.04, P=0.34) in RV dysfunction without PH and 2.52 (95% CI 1.64-3.87, P<0.0001) in RV dysfunction with PH. PH with or without RV dysfunction was associated with increased risk for heart failure. CONCLUSION: In the absence of elevated pulmonary pressures, the risk associated with RV dysfunction after acute myocardial infarction is entirely confined to the first 30 days. Beyond 30 days, PH is the stronger risk factor for long-term mortality and readmission for heart failure. PMID- 27402234 TI - Congenital Heart Disease With and Without Cyanotic Potential and the Long-term Risk of Diabetes Mellitus: A Population-Based Follow-up Study. AB - BACKGROUND: Long-term survival for persons born with congenital heart disease (CHD) is improved, but limited knowledge exists of this growing population's acquired cardiovascular risk profile. This study's purpose was to assess CHD survivors' risk for type 2 diabetes mellitus (T2DM) with attention to the impact of cyanotic CHD. METHODS AND RESULTS: This population-based cohort study included Danish subjects with CHD who were born between 1963 and 1980 and were alive at age 30 years. For each CHD case, we identified 10 individuals from the general population matched by sex and birth year, by using the Danish Civil Registration System. Complete follow-up was obtained through Danish public registries for death, emigration, and T2DM (diagnosis and prescriptions record). We computed cumulative incidences and hazard ratios of developing T2DM after age 30 for 5149 CHD subjects compared with the general population. After adjusting for CHD severity, as well as age, sex, preterm birth, and extracardiac defects, we analyzed the impact of cyanotic compared with acyanotic CHD. By age 45 years, the cumulative incidence of T2DM after age 30 was 4% among subjects with CHD. Subjects with CHD were more likely to develop T2DM than the general population (hazard raio 1.4, 95% CI 1.1-1.6). Subjects CHD who had cyanotic defects were more likely to develop T2DM than were subjects with acyanotic CHD (hazard ratio 1.9, 95% CI 1.1-3.3). CONCLUSIONS: CHD survivors had an increased risk of developing T2DM after age 30. Patients with cyanotic CHD are at particular risk. Given the cardiovascular health burden of T2DM, attention to its development in CHD survivors seems warranted. PMID- 27402235 TI - Sudden Cardiac Death in Patients With Atrial Fibrillation: Insights From the ENGAGE AF-TIMI 48 Trial. AB - BACKGROUND: Recent findings suggest that atrial fibrillation is associated with sudden cardiac death (SCD). We examined the incidence, characteristics, and factors associated with SCD in patients with atrial fibrillation. METHODS AND RESULTS: SCD was defined as witnessed death <=60 minutes from the onset of new symptoms or unwitnessed death 1 to 24 hours after being observed alive, without another known cause of death. Predictors of SCD were examined using multivariate competing risks models. Over 2.8 years (median), 2349 patients died (40.5 per 1000 patient-years), of which 1668 (71%) were cardiovascular deaths. SCD was the most common cause of cardiovascular death (n=749; median age 73 years; 70.6% male). Most SCD events occurred out of hospital (92.8%) and without prior symptoms (66.0%). Predictors of SCD included low ejection fraction, heart failure, and prior myocardial infarction (P<0.001 for each). Additional significant baseline predictors of SCD, but not of other causes of death, included male sex, electrocardiographic left ventricular hypertrophy, higher heart rate, nonuse of beta blockers, and use of digitalis. The latter was associated with SCD in patients with or without heart failure (adjusted hazard ratio 1.55 [95% CI 1.29-1.86] and 1.56 [95% CI 1.14-2.11], respectively; Pinteraction=0.73). The rate of SCD was numerically but not statistically lower with edoxaban (1.20% per year with lower dose edoxaban; 1.28% per year with higher dose edoxaban) compared with warfarin (1.40% per year). CONCLUSION: SCD is the most common cause of cardiovascular death in patients with atrial fibrillation and has several distinct predictors, some of which are modifiable. These findings may be considered in planning research and treatment strategies for patients with atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00781391. PMID- 27402236 TI - Adults Are Not Just Enormous Children: Type 2 Diabetes Mellitus in Adults With Congenital Heart Disease. PMID- 27402238 TI - Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 66, part 2, of the IJSEM. PMID- 27402239 TI - George Alexander McDonald. PMID- 27402237 TI - Design and Rationale of the Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST-CLI) Trial. AB - BACKGROUND: Critical limb ischemia (CLI) is increasing in prevalence, and remains a significant source of mortality and limb loss. The decision to recommend surgical or endovascular revascularization for patients who are candidates for both varies significantly among providers and is driven more by individual preference than scientific evidence. METHODS AND RESULTS: The Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST-CLI) Trial is a prospective, randomized, multidisciplinary, controlled, superiority trial designed to compare treatment efficacy, functional outcomes, quality of life, and cost in patients undergoing best endovascular or best open surgical revascularization. Approximately 140 clinical sites in the United States and Canada will enroll 2100 patients with CLI who are candidates for both treatment options. A pragmatic trial design requires consensus on patient eligibility by at least 2 investigators, but leaves the choice of specific procedural strategy within the assigned revascularization approach to the individual treating investigator. Patients with suitable single-segment of saphenous vein available for potential bypass will be randomized within Cohort 1 (n=1620), while patients without will be randomized within Cohort 2 (n=480). The primary efficacy end point of the trial is Major Adverse Limb Event-Free Survival. Key secondary end points include Re-intervention and Amputation-Free-Survival and Amputation Free Survival. CONCLUSIONS: The BEST-CLI trial is the first randomized controlled trial comparing endovascular therapy to open surgical bypass in patients with CLI to be carried out in North America. This landmark comparative effectiveness trial aims to provide Level I data to clarify the appropriate role for both treatment strategies and help define an evidence-based standard of care for this challenging patient population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02060630. PMID- 27402240 TI - Prescription Patterns and the Cost of Antihyperglycemic Drugs in Patients With Type 2 Diabetes Mellitus in Germany. AB - AIMS: The goals were to analyze prescription patterns and the cost of antihyperglycemic drugs in patients with type 2 diabetes (T2DM) treated in Germany in 2015. METHODS: This study included 36382 patients aged 40 years or over treated in general practices (GPs) and diabetologist practices who were diagnosed with T2DM in 2015. Nine different families of antihyperglycemic therapy were included in the analysis. Demographic data included age, gender, and type of health insurance coverage. Clinical data included HbA1c level, body mass index (BMI), and the number of T2DM complications. The annual antihyperglycemic treatment cost per patient was calculated based on pharmacy retail prices. The multivariate regression analysis was fitted to estimate the adjusted treatment cost differences. RESULTS: The percentage of T2DM patients receiving antihyperglycemic treatments was 87.6. This share was slightly higher in men than in women (89.1% vs 86.0%). Interestingly, the share of people treated with antihyperglycemic drugs decreased with age yet increased with HbA1c levels, BMI, and the number of complications. The average annual cost of antihyperglycemic drugs amounted to ?498. It was significantly higher in men than in women (difference of ?22). It was also significantly higher in individuals with private health insurance coverage than in people with public health insurance coverage (difference of ?153). The annual cost decreased with age. It is compelling to note that this cost increased with HbA1c levels and BMI. Finally, the annual cost also increased with the number of complications. CONCLUSIONS: The share and the cost of antihyperglycemic treatments vary with gender, age, type of health insurance coverage, HbA1c levels, BMI, and the number of complications. PMID- 27402241 TI - A Comprehensive Evaluation of a Novel Color Range Indicator in Multiple Blood Glucose Meters Demonstrates Improved Glucose Range Interpretation and Awareness in Subjects With Type 1 and Type 2 Diabetes. AB - AIMS: We previously demonstrated that people with type 2 diabetes (T2DM) can improve their ability to categorize blood glucose (BG) results into low, in range, or high glycemic ranges after experiencing a color range indicator (CRI or ColorSureTM Technology) in a single meter. This study examined whether a CRI was effective in people with type 1 (T1) or T2DM when used in 3 glucose meters. METHODS: A total of 179 subjects (139 T2DM and 40 T1DM) classified BG values as low, in range, or high based on individual current knowledge. Subjects then experienced the CRI which showed whether different BG values were low, in range, or high. After CRI interaction, subjects repeated the classification. RESULTS: Following interaction with the CRI, subjects significantly improved their ability to categorize BG results into low, in range, and high glycemic ranges by 27.9% (T2DM) and 27.2% (T1DM) (each P < .001). Improvement was not accompanied by an increase in time spent categorizing results. There was no difference in classification ability between subjects with T1 or T2DM. There was also no correlation between HbA1c, numeracy level, test frequency, or duration of diabetes and the ability to correctly classify results. Subjects agreed the CRI feature helped them easily interpret glucose values and improved their awareness of glucose ranges. CONCLUSION: Interaction with a CRI improved the ability of subjects with T1 and T2DM to interpret and categorize BG values into recommended glycemic ranges, irrespective of the glucose meter providing the CRI insights. PMID- 27402242 TI - Screening for Diabetic Retinopathy Using a Portable, Noncontact, Nonmydriatic Handheld Retinal Camera. AB - BACKGROUND: Diabetic retinopathy (DR) is a leading cause of low vision and blindness. We evaluated the feasibility of using a handheld, noncontact digital retinal camera, Pictor, to obtain retinal images in dilated and undilated eyes for DR screening. We also evaluated the accuracy of ophthalmologists with different levels of training/experience in grading these images to identify eyes with vision-threatening DR. METHODS: A prospective study of diabetic adults scheduled to have dilated eye exams at Duke Eye Center from January to May 2014 was conducted. An imager acquired retinal images pre- and postdilation with Pictor and selected 1 pre- and 1 postdilation image per eye. Five masked ophthalmologists graded images for gradability (based on image focus and centration) and the presence of no, mild, moderate, or severe nonproliferative DR (NPDR) or proliferative DR (PDR). Referable disease was defined as moderate or severe NPDR or PDR on image grading. We evaluated feasibility based on the graders' evaluation of image gradability. We evaluated accuracy of identifying vision-threatening disease (severe NPDR or PDR documented on dilated clinical examination) based on the graders' sensitivity and specificity of grading referable disease. RESULTS: Images were gradable in 86-94% of predilation and 94 97% of postdilation photos. Compared to the dilated clinical exam, overall sensitivity for identifying vision-threatening DR was 64-88% and specificity was 71-90%. CONCLUSIONS: Pictor can capture retinal images of sufficient quality to screen for DR with and without dilation. Single retinal images obtained using Pictor can identify eyes with vision-threatening DR with high sensitivity and acceptable specificity compared to clinical exam. PMID- 27402244 TI - Comment on: "Radial head replacement in adults with recent fractures" published by N. Bonnevialle et al. in Orthopaedics & Traumatology: Surgery & Research 2016;102(1 Suppl.):S69-79. PMID- 27402243 TI - Changes in HbA1c and Weight Following Transition to Continuous Subcutaneous Insulin Infusion Therapy in Adults With Type 1 Diabetes. AB - BACKGROUND: Historically, intensive insulin therapy for type 1 diabetes (T1D) has improved glycemic control at the risk of adverse weight gain. The impact of continuous subcutaneous insulin infusion therapy (CSII) on weight in the current era remains unknown. We assessed changes in hemoglobin A1c (HbA1c) and weight in adults with T1D transitioning to CSII at 2 diabetes centers in Denmark and the United States. METHODS: Patients with T1D, aged >=18 years, managed with multiple daily injections (MDI) who transitioned to CSII between 2002 and 2013 were identified using electronic health record data from the Steno Diabetes Center (n = 600) and Joslin Diabetes Center (n = 658). Changes in HbA1c and weight after 1 year was assessed overall and by baseline HbA1c cut points. Multivariate regression assessed correlates of HbA1c reduction. RESULTS: In adults with T1D transitioning to CSII, clinically significant HbA1c reductions were found in patients with baseline HbA1c 8.0-8.9% (Steno, -0.7%; Joslin, -0.4%) and baseline HbA1c >=9.0% (Steno, -1.1%; Joslin, -0.9%) ( P < .005 for all). Overall, there was no significant change in weight after 1 year at either center. Modest (<2%) weight gain was noted in patients with baseline HbA1c >=9% at Steno (1.1 +/- 0.3 kg, P < .0001) and Joslin (1.7 +/- 1.1, P < .005). In multivariate models, HbA1c reduction was associated with higher HbA1c, older age, female sex at Steno ( R2 = .28, P < .005), but only higher baseline HbA1c at Joslin ( R2 = .19, P < .005). CONCLUSION: Adults with T1D with suboptimal glycemic control significantly improved HbA1c without a negative impact on weight 1 year after transitioning from MDI to CSII. PMID- 27402245 TI - Reply to the letter by Liang Cheng, Yong Zhu and Hai-Tao Long. PMID- 27402246 TI - Prophylaxis of vertical HBV infection. AB - INTRODUCTION: An appropriate management of HBV infection is the best strategy to finally reduce the total burden of HBV infection. Mother-to-child transmission (MTCT) is responsible for more than one third of chronic HBV infections worldwide. Because HBV infection in infancy or early childhood often leads to chronic infection, appropriate prophylaxis and management of HBV in pregnancy is crucial to prevent MTCT. AREAS COVERED: The prevention of HBV vertical transmission is a complex task and includes: universal HBV screening of pregnant women, administration of antivirals in the third trimester of pregnancy in women with high viral load and passive-active HBV immunoprophylaxis with hepatitis B vaccine and hepatitis B immune globulin in newborns of all HBV infected women. EXPERT OPINION: Universal screening of pregnant women for HBV infection, early identification of HBV DNA level in HBV-infected mothers, maternal treatment with class B according to FDA antivirals and passive/active anti-HBV immunoprophylaxis to newborns of HBV-positive mothers are crucial strategies for reducing vertical HBV transmission rates. Consideration of caesarean section in order to reduce the risk of vertical HBV transmission should be recommend in HBV infected pregnant women with high viral load despite antiviral therapy or when the therapy in the third trimester of pregnancy is not available. PMID- 27402247 TI - News from the Norwegian Institute of Public Health. PMID- 27402248 TI - Synthesis, solid-state characterization and solution studies of new phytate compounds with Cu(ii) and 1,10-phenanthroline: progress in the structural elucidation of phytate coordinating ability. AB - Within all the eukaryotic cells there is an important group of biomolecules that has been potentially related to signalling functions: myo-inositol phosphates (InsPs). In nature, the most abundant member of this family is the so called phytate (InsP6, L(12-)). The importance of the interaction of InsP6 with cations has been recognized during the last few years, and any attempt to know the function of this molecule in eukaryotic cells must include the fact that InsP6 will be strongly associated with simple inorganic or organic ammonium cations. In this work we expand on our earlier findings by studying the systems phen-phytate (phen = 1,10-phenanthroline) and Cu(ii)-phen-phytate. The structures of (Hphen)4(H8L).7.5H2O and [Cu5(H7L)2(H2O)2(phen)5].23H2O are presented. Solution studies of the binary and ternary systems were also performed by means of potentiometric titrations at 37.0 degrees C and 0.15 M ionic strength. The work was completed with a molecular modelling study. All this information is essential in the process of gaining reliable structural knowledge about the most important InsP6 species in the in vitro and in vivo experiments, and how these features modulate their probable biological functions. PMID- 27402249 TI - Measurement of Hypothalamic Glucose Under Euglycemia and Hyperglycemia by MRI at 3T. AB - PURPOSE: To evaluate the feasibility of using a clinical magnetic resonance (MR) system and MR spectroscopy (MRS) to measure glucose concentration changes in the human hypothalamus, a structure central to whole-body glucose regulation. SUBJECTS AND METHODS: A time series of MR spectra (semi-LASER, TE = 28 msec), localized to the bilateral hypothalamus (~1.6 ml) were obtained at 3T in six healthy subjects at baseline (euglycemia) and during a ~65-70-minute-long hyperglycemic clamp in 11-minute blocks with interleaved T1 FLASH images to retrospectively assess head motion, and track changes in cerebrospinal fluid (CSF) partial volume. The LCModel was used to quantify the sum of glucose and taurine concentrations, [Glc+Tau], along with their associated Cramer-Rao lower bounds (CRLB). RESULTS: Spectral quality allowed quantification of [Glc+Tau] (sum reported due to high negative correlation between these metabolites) with CRLB <25% in 35/36 timepoints during hyperglycemia. Increased [Glc+Tau] was observed with hyperglycemia in all subjects, but most reliably in those with plasma glucose targets >=300 mg/dl. For these subjects, [Glc+Tau]baseline (n = 4) was 1.5 (+/-0.3, SD) mM, and increased to 4.5 (+/-1.1) mM (n = 16) for timepoints acquired >=25 minutes after onset of the clamp, with 15/16 timepoints having no overlap of 95% confidence intervals (CIs) between baseline and hyperglycemia. Preliminary analysis revealed a linear (1:5) relationship between hypothalamus blood glucose concentrations. CONCLUSION: It is feasible to measure glucose concentration changes in the human hypothalamus using a standard 3T scanner and a short-echo semi-LASER sequence by utilizing retrospective motion tracking, CSF correction, predetermined quality acceptance criteria, and hyperglycemic blood glucose levels >=300 mg/dl. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:681-691. PMID- 27402250 TI - Phase 1 Study Assessing the Pharmacokinetic Profile and Safety of Avibactam in Patients With Renal Impairment. AB - Avibactam is a non-beta-lactam beta-lactamase inhibitor intended for use as a fixed-dose combination with ceftazidime for the treatment of certain serious Gram negative infections. As avibactam is primarily excreted unchanged in the urine, renal impairment may affect its pharmacokinetics. This phase 1 study investigated the effect of renal impairment and hemodialysis on avibactam pharmacokinetics and safety. Healthy controls and subjects with increasing degrees of renal impairment received a single 30-minute intravenous (IV) infusion of avibactam (100 mg). Anuric subjects requiring hemodialysis received the same infusion pre- and posthemodialysis, separated by a 7- to 14-day washout. Blood and urine samples were collected, and pharmacokinetics were analyzed using noncompartmental methods. The relationships between avibactam total plasma clearance (CL) or renal clearance (CLR ) and creatinine clearance (CrCL) were evaluated by linear correlation analysis. Safety was also monitored. Increasing severity of renal impairment was associated with decreasing CL and CLR and increasing exposure and terminal half-life (t1/2 ). Avibactam CL and CLR demonstrated an approximately linear relationship with CrCL comparable to that previously observed for ceftazidime. In patients requiring hemodialysis, >50% of the administered avibactam was removed during a 4-hour hemodialysis session, demonstrating that avibactam should be administered after hemodialysis. No new safety findings were reported. To conclude, avibactam dose adjustment is warranted in patients with renal impairment based on the severity of impairment. Because the slope of the linear relationship between avibactam total plasma CL and CrCL is similar to that of ceftazidime, renal impairment dose adjustments should maintain the currently advised 4:1 ratio of ceftazidime:avibactam. PMID- 27402251 TI - ERRalpha mediates metabolic adaptations driving lapatinib resistance in breast cancer. AB - Despite the initial benefits of treating HER2-amplified breast cancer patients with the tyrosine kinase inhibitor lapatinib, resistance inevitably develops. Here we report that lapatinib induces the degradation of the nuclear receptor ERRalpha, a master regulator of cellular metabolism, and that the expression of ERRalpha is restored in lapatinib-resistant breast cancer cells through reactivation of mTOR signalling. Re-expression of ERRalpha in resistant cells triggers metabolic adaptations favouring mitochondrial energy metabolism through increased glutamine metabolism, as well as ROS detoxification required for cell survival under therapeutic stress conditions. An ERRalpha inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mammary tumour mouse model. This work reveals a molecular mechanism by which ERRalpha-induced metabolic reprogramming promotes survival of lapatinib resistant cancer cells and demonstrates the potential of ERRalpha inhibition as an effective adjuvant therapy in poor outcome HER2-positive breast cancer. PMID- 27402252 TI - Desalination of sea water with aquatic lily (Eichhornia crassipes). AB - During the last decades, methods of halo conditioning have been developed to increase the tolerance to salinity in glucophyta crops. Some experiments have carried out the application of hydrogen peroxide (H2O2), in support to the modification of cell tolerance in saline medium. The first objective of this study was to evaluate the effects of the incorporation of H2O2 in salinity tolerance development of the aquatic lily (Eichhornia crassipes). Results showed that the incorporation of 0.03 % H2O2 salinity tolerance developed in salt concentrations similar to seawater. Saline stress tolerance in aquatic lily was shown by the excretion of salts in its leaves; this process helped also in removing salt from seawater. At the same time, the reproduction of the lily is intimately linked to the content of nitrogen (N) and phosphorus (P) (nutrients) in water. This reason is important to control the concentrations of these elements in the water. This will allow maintaining a control in the dissemination of the lily. Considering the mentioned above, the second objective was to continue development of the adaptation of the aquatic lily in seawater, using H2O2 and the required amount of nutrients. This paper points out the importance of considering a biological process for the treatments in the desalination of seawater, making the process more sustainable. PMID- 27402253 TI - Characteristic variation and original analysis of emergent water source pollution accidents in China between 1985 and 2013. AB - China has suffered various water source pollution incidents in the past decades, which have resulted in severe threats to the safety of the water supply for millions of residents. From the aspects of quantity fluctuation, temporal volatility, regional inequality, pollutant category variation, and accident type differences, this study first characterizes the current status of water source contaminations in China by analyzing 340 pollution events for the period spanning from 1985 to 2013. The results show a general increase in the number of accidents during the period 1985-2006 and then a rapid decline starting in 2007. Spring and summer are high-incidence seasons for pollution, and the accident rate in developed southeastern coastal areas is far higher than that in the northwestern regions. Hazardous chemicals and petroleum are the most frequently occurring pollutants, whereas heavy metals and tailings are becoming emerging contaminants during occasional pollutions. Most of the accidents that occurred before 2005 were blamed on illegal emissions or traffic accidents; however, leakage in production has gradually become a major accident type in the past decade. Then, in combination with government actions and policy constraints, this paper explores the deep inducements and offers valuable insight into measures that should be taken to ensure future prevention and mitigation of emergent source water pollution. PMID- 27402254 TI - Assessment of mercury contamination based on mercury distribution in sediment, macroalgae, and seagrass in the Todos os Santos bay, Bahia, Brazil. AB - The Todos os Santos bay (TSB) is the second largest Brazilian bay. Despite the large number of potential anthropogenic sources of mercury (Hg) in the bay, data on this element in this marine environment are very scarce. Total Hg concentrations were therefore determined in sediment, macroalgae, and seagrass species collected during dry and rainy seasons, from eight locations. In ~45 % of the sediment samples, Hg concentration was two to four times higher than the upper value considered the regional Hg background (15 MUg kg(-1)). Geoaccumulation index indicated that Hg contamination was at none to heavily contaminated. In Padina sp., Caulerpa sp., Hypnea sp., and Halodule wrigthii, Hg concentrations ranged from 10.61-297.61, 15.59-74.50, 12.84-158.03, and 4.02 67.25 MUg kg(-1), respectively. PMID- 27402256 TI - Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds. AB - Granulation tissue formation requires a robust angiogenic response. As granulation tissue develops, collagen fibers are deposited and compacted. Forces generated in the wake of this process drive wound contraction to reduce the wound area. In diabetics, both angiogenesis and wound contraction are diminished leading to impaired wound healing. To emulate this pathology and to address it pharmacologically, we developed a wound healing model in the diabetic Zucker fatty rat and tested a topical proangiogenic strategy combining antifungal agent ciclopirox olamine (CPX) and lysophospholipid sphingosine-1-phosphate (S1P) to promote diabetic wound closure. In vitro, we demonstrated that CPX + S1P up regulates a crucial driver of angiogenesis, hypoxia-inducible factor-1, in endothelial cells. Injection of CPX + S1P into subcutaneously implanted sponges in experimental rats showed, in an additive manner, a fivefold increased endothelial infiltration and lectin-perfused vessel length. We developed a splinted diabetic rodent model to achieve low wound contraction rates that are characteristic for the healing mode of diabetic ulcers in humans. We discovered specific dorsal sites that allowed for incremental full-thickness excisional wound depths from 1 mm (superficial) to 3 mm (deep). This enabled us to bring down wound contraction from 51% in superficial wounds to 8% in deep wounds. While the effects of topical gel treatment of CPX + S1P were masked by the rodent characteristic dominant contraction in superficial wounds, they became clearly evident in deep diabetic wounds. Here, a fivefold increase of functional large vessels resulted in accelerated granulation tissue formulation, accompanied by a 40% increase of compacted thick collagen fibers. This was associated with substantially reduced matrix metalloproteinase-3 and -13 expression. These findings translated into a fivefold increase in granulation-driven contraction, promoting diabetic wound closure. With CPX and S1P analogues already in clinical use, their combination presents itself as an attractive proangiogenic treatment to be repurposed for diabetic wound healing. PMID- 27402255 TI - An on-site audit system for dosimetry credentialing of intensity-modulated radiotherapy in Japanese Clinical Oncology Group (JCOG) clinical trials. AB - PURPOSE: This study was undertaken to analyze the results of intensity-modulated radiotherapy (IMRT) dosimetry credentialing using a phantom in the Japanese Clinical Oncology Group clinical trials. METHODS: All measurements were performed on-site. The IMRT phantom consisted of a phantom shell and a module. Two types of structures, including a C-shaped planning target volume (PTV) around a column shaped organ at risk (OAR), were included in the module. Each participating institution was asked to image, plan, and treat the phantom. A prescription dose of 2Gy should cover 95% of the PTV. The plan should limit the maximum doses to the PTV and OAR to less than 110% and 60%, respectively. The pass criteria were +/-3% in terms of chamber dosimetry and a difference in profile position ?2mm in the high-dose gradient area of film dosimetry. The positional difference was defined as the largest distance between the measured and calculated positions at doses of 60% or 80%. These tolerances were based on the Japanese Society for Radiation Oncology IMRT guidelines. RESULTS: Credentialing was performed on a total of 44 treatment machines in 32 institutions from 2009 to 2015. All differences between measured and planned doses at the measurement points of the PTV were within 3%. The means+/-standard deviations of the positional differences were 1.0+/-0.4mm and 0.9+/-0.3mm without and with the phantom shell, respectively. CONCLUSIONS: The dose differences and positional differences met the desired criteria in all institutions. PMID- 27402257 TI - Secretomic analysis of extracellular vesicles originating from polyomavirus negative and polyomavirus-positive Merkel cell carcinoma cell lines. AB - Extracellular vesicles or exosomes constitute an evolutionarily conserved mechanism of intercellular signaling. Exosomes are gaining an increasing amount of attention due to their role in pathologies, including malignancy, their importance as prognostic and diagnostic markers, and their potential as a therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. Because an effective systemic treatment for this cancer type is currently not available, an exosome-based therapy was proposed. However, comprehensive secretome profiling has not been performed for MCC. To help unveil the putative contribution of exosomes in MCC, we studied the protein content of MCC-derived exosomes. Since approximately 80% of all MCC cases contain Merkel cell polyomavirus (MCPyV), the secretomes of two MCPyV-negative and two MCPyV-positive MCC cell lines were compared. We identified with high confidence 164 exosome-derived proteins common for all four cell lines that were annotated in ExoCarta and Vesiclepedia databases. These include proteins implicated in motility, metastasis and tumor progression, such as integrins and tetraspanins, intracellular signaling molecules, chaperones, proteasomal proteins, and translation factors. Additional virus-negative and virus-positive MCC cell lines should be examined to identify highly representative exosomal proteins that may provide reliable prognostic and diagnostic biomarkers, as well as targets for treatment in the future. Data are available via ProteomeXchange with identifier PXD004198. PMID- 27402258 TI - EXA1, a GYF domain protein, is responsible for loss-of-susceptibility to plantago asiatica mosaic virus in Arabidopsis thaliana. AB - One of the plant host resistance machineries to viruses is attributed to recessive alleles of genes encoding critical host factors for virus infection. This type of resistance, also referred to as recessive resistance, is useful for revealing plant-virus interactions and for breeding antivirus resistance in crop plants. Therefore, it is important to identify a novel host factor responsible for robust recessive resistance to plant viruses. Here, we identified a mutant from an ethylmethane sulfonate (EMS)-mutagenized Arabidopsis population which confers resistance to plantago asiatica mosaic virus (PlAMV, genus Potexvirus). Based on map-based cloning and single nucleotide polymorphism analysis, we identified a premature termination codon in a functionally unknown gene containing a GYF domain, which binds to proline-rich sequences in eukaryotes. Complementation analyses and robust resistance to PlAMV in a T-DNA mutant demonstrated that this gene, named Essential for poteXvirus Accumulation 1 (EXA1), is indispensable for PlAMV infection. EXA1 contains a GYF domain and a conserved motif for interaction with eukaryotic translation initiation factor 4E (eIF4E), and is highly conserved among monocot and dicot species. Analysis using qRT-PCR and immunoblotting revealed that EXA1 was expressed in all tissues, and was not transcriptionally responsive to PlAMV infection in Arabidopsis plants. Moreover, accumulation of PlAMV and a PlAMV-derived replicon was drastically diminished in the initially infected cells by the EXA1 deficiency. Accumulation of two other potexviruses also decreased in exa1-1 mutant plants. Our results provided a functional annotation to GYF domain-containing proteins by revealing the function of the highly conserved EXA1 gene in plant-virus interactions. PMID- 27402260 TI - Extracting Information from Electronic Medical Records to Identify the Obesity Status of a Patient Based on Comorbidities and Bodyweight Measures. AB - Obesity is a chronic disease with an increasing impact on the world's population. In this work, we present a method of identifying obesity automatically using text mining techniques and information related to body weight measures and obesity comorbidities. We used a dataset of 3015 de-identified medical records that contain labels for two classification problems. The first classification problem distinguishes between obesity, overweight, normal weight, and underweight. The second classification problem differentiates between obesity types: super obesity, morbid obesity, severe obesity and moderate obesity. We used a Bag of Words approach to represent the records together with unigram and bigram representations of the features. We implemented two approaches: a hierarchical method and a nonhierarchical one. We used Support Vector Machine and Naive Bayes together with ten-fold cross validation to evaluate and compare performances. Our results indicate that the hierarchical approach does not work as well as the nonhierarchical one. In general, our results show that Support Vector Machine obtains better performances than Naive Bayes for both classification problems. We also observed that bigram representation improves performance compared with unigram representation. PMID- 27402259 TI - Relation of longitudinal changes in body mass index with atherosclerotic cardiovascular disease risk scores in middle-aged black and white adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. AB - PURPOSE: We assessed whether longitudinal changes in body mass index (BMI) are positively associated with changes in 10-year American College of Cardiology/American Heart Association atherosclerotic cardiovascular disease (ASCVD) risk scores in middle-aged blacks compared to whites. METHODS: Data were from 1691 participants enrolled in the Coronary Artery Risk Development in Young Adults Study aged 40 years or more in 2000-2001, who had follow-up examinations 5 and 10 years later. RESULTS: The prevalence of obesity increased from 32.3% in 2000-2001 (mean age: 42.8 years) to 41.7% in 2010-2011, higher in blacks than whites. The corresponding change in 10-year ASCVD risk was significantly higher for blacks (men: 4.5%-9.6%, women: 1.7%-5.0%) than whites (men: 2.4%-5.2%, women: 0.7%-1.6%). In 2010-2011, 57.5% of black men had ASCVD risk scores of 7.5% or more compared to white men (14.7%), black women (17.4%), and white women (1.6%). Although BMI trends were positively associated with 10-year change in ASCVD risk scores (0.07% per 1 kg/m(2) increase), it explained very little variance in risk score trends in all race-sex groups. CONCLUSIONS: In middle-aged adults, longitudinal changes in BMI had little independent influence on changes in 10 year ASCVD risk scores as its effect may be largely mediated through ASCVD risk factors already accounted for in the risk score. PMID- 27402261 TI - Generalist palliative care for non-cancer patients : A review article. AB - BACKGROUND: Most patients in the last phase of life can be treated in the context of generalist palliative care, especially by general practitioners. In contrast to specialized palliative care, non-cancer patients predominate in this setting. OBJECTIVE: The aim of this article is to review the literature and elaborate current topics for non-cancer patients at the end-of-life in primary palliative care. MATERIALS AND METHODS: A literature search was carried out in the databases PubMed and Scopus from 2008 to 2013 followed by a qualitative content analysis according to the PRISMA statement. RESULTS: A total of 127 articles could be included in the qualitative content analysis and the final review whereby four core topics were identified: (1) specific target groups (e. g. elderly patients, patients with advanced heart failure and pain), (2) collaboration of general practitioners with other physicians and health professionals, (3) qualifications in palliative care and (4) provision of primary palliative care. Most articles found were related to the fourth topic and the subtopic of barriers and facilitators of palliative care. Insufficient coordination of the persons involved was a barrier often discussed. Advanced care planning including concrete palliative care aspects at an early stage can be beneficial for both patients and professionals. CONCLUSION: The current literature search highlights the importance of optimizing the processes and structures in providing palliative care and the discussion of end-of-life issues at an early stage in general practice. Therefore, a structured identification of palliative care needs identified by appropriate assessment instruments is crucial. PMID- 27402262 TI - [Pain and analgesia : Mutations of voltage-gated sodium channels]. AB - Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures. For the last ten years, Nav1.7 has been the main focus of clinical interest, as a large number of hereditary mutants were identified. The so-called "gain-of-function" mutations of Nav1.7 cause the pain syndromes hereditary erythromelalgia and paroxysmal extreme pain disorder. In addition, several Nav1.7 mutants were shown to be associated with small-fiber neuropathies. On the contrary, "loss-of function" Nav1.7 mutants lead to a congenital insensitivity to pain. Recently, several gain-of-function mutations in Nav1.8 and Nav1.9 have been identified in patients suffering from painful peripheral neuropathies. However, another gain-of function Nav1.9 mutation is associated with congenital insensitivity to pain. This review offers an overview of published work on painful Nav mutations with clinical relevance, and proposes possible consequences for the therapy of different pain symptoms resulting from these findings. PMID- 27402263 TI - [Placebo response - Mechanisms and clinical applications]. AB - Research on placebo responses has made major progress in recent years. Placebo responses are psychobiological events, which are created by the entire therapeutic context. They can appear at any time, not only in experimental and clinical settings. Several studies on analgesia-related placebo research showed that patients have higher placebo responses in comparison to healthy participants, which may also last longer. Expectations play a key role in placebo analgesia. They can be induced via three central psychological mechanisms: 1) expectation induced via instructions, 2) expectation induced via classical conditioning and 3) expectation induced via social learning. These mechanisms are controlled by neurobiological structures and modulate pain perception resulting in pain relief by positive expectations and increased pain by negative expectations, the so-called nocebo effect. There is an ongoing discussion that these psychological mechanisms may also play a central role in inducing and maintaining itch-reducing placebo responses. The current state of research suggests that placebo responses could be used in clinical contexts and should not be viewed as being in competition with medications but as an additive increase in efficacy of a pharmacological substance through specifically induced placebo responses. This targeted use is also possible within ethical guidelines. Important prerequisites are that the research results can be transferred from healthy participants to patients and that the placebo responses are reproducible. PMID- 27402264 TI - [High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)]. AB - BACKGROUND: High-intensity focused ultrasound (HIFU) in combination with palliative standard therapy is an innovative and effective treatment option for pain reduction in patients with inoperable pancreatic cancer. OBJECTIVE: Evaluation of the effects of additive ultrasound (US)-guided HIFU treatment in inoperable pancreatic cancer on the sensory and affective pain perception using validated questionnaries. MATERIAL AND METHODS: In this study 20 patients with locally advanced inoperable pancreatic cancer and tumor-related pain were treated by US-guided HIFU (6 stage III, 12 stage IV according to UICC and 2 with local recurrence after surgery). Ablation was performed using the JC HIFU system (HAIFU, Chongqing, China) with an ultrasonic device for real-time imaging. Clinical assessment included evaluation of pain severity using validated questionnaires with particular attention to the pain sensation scale (SES) with its affective and sensory component and the numeric rating scale (NRS). RESULTS: The average pain reduction after HIFU was 2.87 points on the NRS scale and 57.3 % compared to the mean baseline score (n = 15, 75 %) in 19 of 20 treated patients. Four patients did not report pain relief, however, the previous opioid medication could be stopped (n = 2) or the analgesic dosage could be reduced (n = 2). No pain reduction was achieved in one patient. Furthermore, after HIFU emotional as well as sensory pain aspects were significantly reduced (before vs. 1 week after HIFU, p < 0.05 for all pain scales). CONCLUSION: US-guided HIFU can be used for effective and early pain relief and reduction of emotional and sensory pain sensation in patients with locally advanced pancreatic cancer. PMID- 27402265 TI - [Chronic pain care : Reality and entitlement]. AB - From the point of view of healthcare policies, improvement in pain care has been required for years; however, there is a great discrepancy between the current need for pain care and the actual provision by healthcare services. This article seeks to demonstrate that while healthcare policies are one of the critical factors involved, a variety of conceptual, diagnostic and therapeutic causes should also be taken into account. Firstly, considering that pain care is primarily concerned with the suffering of pain by patients, the focus lies with their conscious experience in order to define the patients' understanding of pain. Additionally, in this article current biomedical and psychosocial comprehension concerning chronic pain will be illustrated and why it is necessary to broaden our horizons in order to do justice to patients with chronic pain. PMID- 27402266 TI - Overexpression of GhSARP1 encoding a E3 ligase from cotton reduce the tolerance to salt in transgenic Arabidopsis. AB - Ubiquitination plays a very important role in the response to abiotic stresses of plant. To identify key regulators of salt stress, a gene GhSARP1(Salt-Associated Ring finger Protein)encoding C3H2C3-type E3 ligase, was cloned from cotton. Transcription level of GhSARP1 was high in leaf, flower and fiber of 24,27 and 27DPA (Days Post-Anthesis), but low in root and stem. Except PEG6000 treatment, the expression of GhSARP1 was down-regulated by NaCl, cold and ABA after being treated for 1 h. GhSARP1-GFP fusion protein located on the plasma membrane, which was dependent on trans-membrane motif. In vitro ubiquitination assay showed that GhSARP1 had E3 ligase activity. Heterogeneous overexpression of GhSARP1reduced salt tolerance of transgenic Arabidopsis in germination and post-germination stage. Our results suggested that the GhSARP1 might negatively regulate the response to salt stress mediated by the ubiquitination in cotton. PMID- 27402267 TI - TAGLN2, a novel regulator involved in Hepatitis B virus transcription and replication. AB - Hepatitis B virus (HBV) infection is one of the major health problems in the world. Transgelin-2 (TAGLN2) expression has been revealed to be significantly altered in previous studies concerning HBV-host interaction. The present study investigated TAGLN2 expression patterns in HBV related hepatocellular carcinoma (HCC) tissues and its role in HBV transcription and replication. We collected 59 HBV related HCC tissue samples, their adjacent non-tumoral tissues and 16 normal livers to make the tissue microarray. TAGLN2 protein was detected by immunohistochemistry and the transcriptional levels of TAGLN2, HBc, HBs and HBx were detected by qRT-PCR. Then we investigated the function of TAGLN2 on HBV transcription and replication in vitro by ectopic expressing or knocking down TAGLN2 in HepG2 and HepG2.2.15 cell lines. We further studied the effect of HBx on TAGLN2 expression with a Tet-on HBx expressing cell line. TAGLN2 protein expression was lower in normal livers and HBV-HCC tissues comparing to adjacent non-tumoral tissues. The transcriptional levels of TAGLN2 in HBV-HCC tissues and their adjacent tissues were positively related to that of HBc, HBs and HBx (P < 0.05). Ectopic expression of TAGLN2 in vitro could enhance HBV transcription and replication while suppressing TAGLN2 had the contrary effect. TAGLN2 could be induced by HBx in a dose-dependent manner. Our data demonstrated that TAGLN2 might be an HBx induced positive host factor involved in HBV transcription and replication and HBx related liver fibrosis and tumorigenesis. PMID- 27402268 TI - BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice. AB - Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERalpha and ERbeta. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. PMID- 27402269 TI - Rosmarinic Acid suppressed high glucose-induced apoptosis in H9c2 cells by ameliorating the mitochondrial function and activating STAT3. AB - Mitochondrial injury characterized by intracellular reactive oxygen species (ROS) accumulation plays a critical role in hyperglycemia-induced myocardium dysfunction. Previous studies have demonstrated that Rosmarinic Acid (RA) treatment and activating Signal transducer and activator of transcription 3 (STAT3) signaling pathway have protective effects on mitochondrial dysfunction in cardiomyocyte, but there is little data regarding cardiomyocyte under condition of high-glucose. The present study was undertaken to determine the relationship between RA and STAT3 activation, as well as their effects on high glucose-induced mitochondrial injury and apoptosis in H9c2 cardiomyocyte. Our results revealed that RA pretreatment suppressed high glucose-induced apoptosis in H9c2 cells. Moreover, the effect of RA on apoptosis was related with improved mitochondrial function, which was demonstrated by that RA attenuated high glucose-induced ROS generation, inhibited mitochondrial permeability transition pore (MPTP) activation, suppressed cytochrome c release and caspase-3 activation. In addition, the phosphorylation of STAT3 in H9c2 cells was inhibited under condition of high-glucose, but RA improved STAT3 phosphorylation. Importantly, inhibition of STAT3 expression by using STAT3-siRNA partly suppressed the effect of RA on high glucose-induced apoptosis. Taken together, pretreatment with RA suppressed high glucose-induced apoptosis in cardiomyocyte by ameliorating mitochondrial function and activating STAT3. PMID- 27402270 TI - Magnesium inhibits the calcification of the extracellular matrix in tendon derived stem cells via the ATP-P2R and mitochondrial pathways. AB - Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg(2+)/Ca(2+) balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP-P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg(2+) ([Mg(2+)]e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 MUM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg(2+)]e levels. A high [Mg(2+)]e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg(2+) and Ca(2+) is therefore contradictory, Mg(2+) inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca(2+). JC-1 staining verified the protective effect of Mg(2+) on mitochondrial membrane potential and the decrease induced by Ca(2+). Taken together, these results indicate that high [Mg(2+)]e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg(2+) and Ca(2+) influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs. PMID- 27402271 TI - Repin1 deficiency improves insulin sensitivity and glucose metabolism in db/db mice by reducing adipose tissue mass and inflammation. AB - Replication initiator 1 (Repin1) is a zinc finger protein playing a role in insulin sensitivity, body fat mass and lipid metabolism by regulating the expression key genes of glucose and lipid metabolism. Here, we tested the hypothesis that introgression of a Repin1 deletion into db/db mice improves glucose metabolism in vivo. We generated a whole body Repin1 deficient db/db double knockout mouse (Rep1(-/-)x db/db) and systematically characterized the consequences of Repin1 deficiency on insulin sensitivity, glucose and lipid metabolism parameters and fat mass. Hyperinsulinemic-euglycemic clamp studies revealed significantly improved insulin sensitivity in Rep1(-/-)x db/db mice, which are also characterized by lower HbA1c, lower body fat mass and reduced adipose tissue (AT) inflammation area. Our study provides evidence that loss of Repin1 in db/db mice improves insulin sensitivity and reduces chronic hyperglycemia most likely by reducing fat mass and AT inflammation. PMID- 27402273 TI - A novel alkaloid, evodiamine causes nuclear localization of cytochrome-c and induces apoptosis independent of p53 in human lung cancer cells. AB - Lung cancer is the most frequently diagnosed malignancy that contributes to high proportion of deaths globally among patients who die due to cancer. Chemotherapy remains the common mode of treatment for lung cancer patients though with limited success. We assessed the biological effects and associated molecular changes of evodiamine, a plant alkaloid, on human lung cancer A549 and H1299 cells along with other epithelial cancer and normal lung SAEC cells. Our data showed that 20 40 MUM evodiamine treatment for 24-48 h strongly (up to 73%, P < 0.001) reduced the growth and survival of these cancer cells. However, it also moderately inhibited growth and survival of SAEC cells. A strong inhibition (P < 0.001) was observed on clonogenicity of A549 cells. Further, evodiamine increased (4-fold) mitochondrial membrane depolarization with 6-fold increase in apoptosis and a slight increase in Bax/Bcl-2 ratio. It increased the cytochrome-c release from mitochondria into the cytosol as well as nucleus. Cytosolic cytochrome-c activated cascade of caspase-9 and caspase-3 intrinsic pathway, however, DR5 and caspase-8 extrinsic pathway was also activated which could be due to nuclear cytochrome-c. Pan-caspase inhibitor (z-VAD.fmk) partially reversed evodiamine induced apoptosis. An increase in p53 as well as its serine 15 phosphorylation was also observed. Pifithrin-alpha, a p53 inhibitor, slightly inhibited growth of A549 cells and under p53 inhibitory condition evodiamine-induced apoptosis could not be reversed. Together these findings suggest that evodiamine is a strong inducer of apoptosis in lung epithelial cancer cells independent of their p53 status and that could involve both intrinsic as well as extrinsic pathway of apoptosis. Thus evodiamine could be a potential anticancer agent against lung cancer. PMID- 27402272 TI - Effect of glucocorticoid withdrawal on glucocorticoid inducing bone impairment. AB - Glucocorticoid (GC) withdrawal after a short-term use was common in clinical practice like immediate post-transplant period. However, previous studies without setting age-control group failed to determine whether the BMD recovery was sufficient and whether it is necessary to accept anti-osteoporosis therapy after GC withdrawal. The aim of this study was to investigate the effect of GC withdrawal on bone impairment in glucocorticoid-induced osteoporosis (GIOP) rats. Twenty-four female Sprague-Dawley rats (3 months' old) were randomly divided into two treatment groups: an untreated age-control group (Con, n = 12); another group receiving a dexamethasone injection (DEXA, n = 12). Animals in the Con group were euthanized at 3rd month (M3) and 6th month (M6), respectively. Six rats in the DEXA group were euthanized at 3rd month (M3), whereas GC intervention was withdrew in the remaining animals of DEXA group, which were euthanized at the end of 6th month (M6). Bone mass, bone microarchitecture, biomechanical properties of vertebrae, morphology, serum levels of PINP and beta-CTX were evaluated. Compared with the Con(M3) group, the Con(M6) group showed significantly better bone quantity, morphology and quality. Compared with the Con(M3) group, the DEXA (M3) group showed significantly lower BMC, BMD, BS/TV, BV/TV, Tb.N, Tb.Th, vBMD, bone strength, compressive displacement, energy absorption capacity, PINP levels, beta CTX levels, and damaged trabecular morphology. And the same change trend was observed in the comparison between the Con(M6) group and DEXA (M6) group. Compared with the DEXA (M3) group, the DEXA (M6) group showed significantly higher BMC, BMD and AREA, but no significant difference in BS/TV, BV/TV, SMI, Tb.N, Tb.Th, Tb.Sp, vBMD, bone strength, bone stiffness, compressive displacement, energy absorption capacity, PINP levels, beta-CTX levels, and improvement in trabecular morphology was observed. These results indicate that the reverse effect of GC withdrawal for 3 months on bone impairment in GIOP rats was insufficient, which implied that related anti-osteoporosis treatment might be still necessitated after GC withdrawal in clinical setting. PMID- 27402274 TI - Increase of p25 associated with cortical neuronal death induced by hypoxia. AB - The mechanisms of neuronal damage in hypoxic cerebral cortex are complicated. Recent studies indicated that deregulation of Cdk5 was involved in neuronal death induced by hypoxia (1% O2). However, the pathological effect of Cdk5 is not fully elucidated. Therefore, in order to decipher the effect of Cdk5 on cellular death in hypoxic condition, the Cdk5 and its activator p35/p25 were investigated in cortical neurons at 10 DIV (Days In Vitro). Upon exposure to hypoxia, the cortical neurons showed a time-dependent increase of neuronal death compared to normoxia-treated control neurons. In correlation to the increase of neuronal death under hypoxia, the level of p25, a truncated form of p35, also increased in a time-dependent manner. Importantly, inhibition of Cdk5 kinase activity by roscovitine protected neurons from death under hypoxic stress. In contrast, ectopic upregulation of Cdk5 kinase activity in neurons expressing p25 led to an increase of neuronal death in comparison to control neurons expressing GFP. It suggests that ectopic increase of Cdk5 kinase activity through conversion of p35 to p25 is involved in the process of neuronal death induced by hypoxia. PMID- 27402275 TI - Deciphering the roles of circRNAs on chilling injury in tomato. AB - Various circular RNAs (circRNAs) are newly identified in animals and plants through high-throughput deep sequencing which play important roles in miRNA function and transcriptional controlling. However, little is known regarding circRNAs in tomato fruit. In this study, we systematically parse the circRNAs in the whole genome using the combination methods of deep sequencing and bioinformatics. In all, 854 circRNAs were identified in our results, among them, 163 circRNAs exhibit chilling responsive expression. Intriguingly, several circRNAs were predicted to involved in chilling responsive process, such as redox reaction, cell wall degradation, Arginine and polyamine metabolism, heat and cold shock protein, energy metabolism, Jasmonic acid and abscisic acid metabolism, low temperature and salt responsive protein and low temperature-induced transcription factors(CBF and WRKY). Furthermore, 102 circRNAs were found to act as the corresponding 24 miRNAs sponges in tomato. These discoveries deciphered the unexpected complexity of the regulatory circRNAs and may open a window for understanding the functions of circRNAs in plants. PMID- 27402276 TI - Neutrophil swarming toward Cryptococcus neoformans is mediated by complement and leukotriene B4. AB - Swarming behavior of neutrophils has been noticed in both sterile injury and infection models and the mechanisms are being unveiled. So far, no in vitro model has been established to study neutrophil swarming to microbes. In the current study, using live-cell imaging, we observed in vitro neutrophil swarming toward Cryptococcus neoformans, a fungal pathogen causing human meningoencephalitis. Complement C3 and CD11b expression are essential for neutrophils to form cell swarms surrounding C. neoformans. Leukotriene B4 (LTB4) was quickly released by neutrophils during their interactions with C. neoformans. Blockade of LTB4 synthesis inhibited the swarming response to C. neoformans. Importantly, blockade of LTB4 synthesis also significantly reduced neutrophil recruitment in the lung vasculature of mice infected intravenously with C. neoformans, demonstrating a critical role of LTB4 in intravascular neutrophil swarming during infection. Together, this is the first report of neutrophil dynamics of swarming toward a microorganism in vitro, mediated by complement and LTB4. PMID- 27402277 TI - Acetaminophen Attenuates House Dust Mite-Induced Allergic Airway Disease in Mice. AB - Epidemiologic evidence suggests that N-acetyl-para-aminophenol (APAP) may play a role in the pathogenesis of asthma, likely through pro-oxidant mechanisms. However, no studies have investigated the direct effects of APAP on the development of allergic inflammation. To determine the likelihood of a causal relationship between APAP and asthma pathogenesis, we explored the effects of APAP on inflammatory responses in a murine house dust mite (HDM) model of allergic airway disease. We hypothesized that APAP would enhance the development of HDM-induced allergic inflammation. The HDM model consisted of once daily intranasal instillations for up to 2 weeks with APAP or vehicle administration 1 hour prior to HDM during either week 1 or 2. Primary assessment of inflammation included bronchoalveolar lavage (BAL), cytokine expression in lung tissue, and histopathology. Contrary to our hypothesis, the effects of HDM treatment were substantially diminished in APAP-treated groups compared with controls. APAP treated groups had markedly reduced airway inflammation: including decreased inflammatory cells in the BAL fluid, lower cytokine expression in lung tissue, and less perivascular and peribronchiolar immune cell infiltration. The anti inflammatory effect of APAP was not abrogated by an inhibitor of cytochrome P450 (P450) metabolism, suggesting that the effect was due to the parent compound or a non-P450 generated metabolite. Taken together, our studies do not support the biologic plausibility of the APAP hypothesis that APAP use may contribute to the causation of asthma. Importantly, we suggest the mechanism by which APAP modulates airway inflammation may provide novel therapeutic targets for asthma. PMID- 27402278 TI - Integrated Strategy for Use of Positron Emission Tomography in Nonhuman Primates to Confirm Multitarget Occupancy of Novel Psychotropic Drugs: An Example with AZD3676. AB - Positron emission tomography (PET) is widely applied in central nervous system (CNS) drug development for assessment of target engagement in vivo. As the majority of PET investigations have addressed drug interaction at a single binding site, findings of multitarget engagement have been less frequently reported and have often been inconsistent with results obtained in vitro. AZD3676 [N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl) benzofuran-2 carboxamide] is a novel combined serotonin (5-hydroxytryptamine) 5-HT1A and 5 HT1B receptor antagonist that was developed for the treatment of cognitive impairment in Alzheimer's disease. Here, we evaluated the properties of AZD3676 as a CNS drug by combining in vitro and ex vivo radioligand binding techniques, behavioral pharmacology in rodents, and PET imaging in nonhuman primates. Target engagement in the nonhuman primate brain was assessed in PET studies by determination of drug-induced occupancy using receptor-selective radioligands. AZD3676 showed preclinical properties consistent with CNS drug potential, including nanomolar receptor affinity and efficacy in rodent models of learning and memory. In PET studies of the monkey brain, AZD3676 inhibited radioligand binding in a dose-dependent manner with similar affinity at both receptors. The equally high affinity at 5-HT1A and 5-HT1B receptors as determined in vivo was not predicted from corresponding estimates obtained in vitro, suggesting more than 10-fold selectivity for 5-HT1A versus 5-HT1B receptors. These findings support the further integrated use of PET for confirmation of multitarget occupancy of CNS drugs. Importantly, earlier introduction of PET studies in nonhuman primates may reduce future development costs and the requirement for animal experiments in preclinical CNS drug development programs. PMID- 27402280 TI - A cadaveric mechanical study of forearm stability after a new stabilizing procedure. PMID- 27402279 TI - Task- and Treatment Length-Dependent Effects of Vortioxetine on Scopolamine Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats. AB - Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine's ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine's effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine's pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine's moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine's cognitive effects, which are observed under chronic dosing conditions in patients with MDD. PMID- 27402281 TI - Minimally invasive stabilization of the distal radioulnar joint: a cadaveric study. AB - This study describes a minimally invasive procedure for stabilization of the distal radioulnar joint, using a suture-button construct placed percutaneously in the direction of the distal oblique bundle in the distal interosseous membrane. In five cadaveric specimens, placement of the suture-button suspension system reduced dorsal displacement of the radius in an unstable distal radioulnar joint to baseline values, both in neutral position and in pronation and supination. These results indicate the possibility of minimally invasive treatment for distal radioulnar joint instability. PMID- 27402282 TI - Does sensory relearning improve tactile function after carpal tunnel decompression? A pragmatic, assessor-blinded, randomized clinical trial. AB - : Despite surgery for carpal tunnel syndrome being effective in 80%-90% of cases, chronic numbness and hand disability can occur. The aim of this study was to investigate whether sensory relearning improves tactile discrimination and hand function after decompression. In a multi-centre, pragmatic, randomized, controlled trial, 104 patients were randomized to a sensory relearning ( n = 52) or control ( n = 52) group. A total of 93 patients completed a 12-week follow-up. Primary outcome was the shape-texture identification test at 6 weeks. Secondary outcomes were touch threshold, touch localization, dexterity and self-reported hand function. No significant group differences were seen for the primary outcome (Shape-Texture Identification) at 6 weeks or 12 weeks. Similarly, no significant group differences were observed on secondary outcomes, with the exception of self reported hand function. A secondary complier-averaged-causal-effects analysis showed no statistically significant treatment effect on the primary outcome. Sensory relearning for tactile sensory and functional deficits after carpal tunnel decompression is not effective. LEVEL OF EVIDENCE: II. PMID- 27402283 TI - Effect of ice on pain after corticosteroid injection in the hand and wrist: a randomized controlled trial. AB - : This prospective, randomized controlled study was designed to determine if applying ice to the site of corticosteroid injections in the hand and wrist reduces post-injection pain. Patients receiving corticosteroid injections in the hand or wrist at a tertiary institution were enrolled. Subjects were randomized to apply ice to the injection site and take scheduled over-the-counter analgesics ( n = 36) or take scheduled over-the-counter analgesics alone ( n = 32). There were no significant differences in the mean pain score between the two groups at any time-point (pre-injection or 1-5 days post-injection). In regression modelling, the application of ice did not predict pain after injection. Visual analogue pain scores increased at least 2 points (0-10 scale) after injection in 17 out of 36 patients in the ice group versus ten out of 32 control patients. We conclude that the application of ice in addition to over-the-counter analgesics does not reduce post-injection pain after corticosteroid injection in the hand or wrist. LEVEL OF EVIDENCE: I Therapeutic Study. PMID- 27402284 TI - Do saline taxa evolve faster? Comparing relative rates of molecular evolution between freshwater and marine eukaryotes. AB - The major branches of life diversified in the marine realm, and numerous taxa have since transitioned between marine and freshwaters. Previous studies have demonstrated higher rates of molecular evolution in crustaceans inhabiting continental saline habitats as compared with freshwaters, but it is unclear whether this trend is pervasive or whether it applies to the marine environment. We employ the phylogenetic comparative method to investigate relative molecular evolutionary rates between 148 pairs of marine or continental saline versus freshwater lineages representing disparate eukaryote groups, including bony fish, elasmobranchs, cetaceans, crustaceans, mollusks, annelids, algae, and other eukaryotes, using available protein-coding and noncoding genes. Overall, we observed no consistent pattern in nucleotide substitution rates linked to habitat across all genes and taxa. However, we observed some trends of higher evolutionary rates within protein-coding genes in freshwater taxa-the comparisons mainly involving bony fish-compared with their marine relatives. The results suggest no systematic differences in substitution rate between marine and freshwater organisms. PMID- 27402285 TI - Food and pathogen adaptations in the Angolan Namib desert: Tracing the spread of lactase persistence and human African trypanosomiasis resistance into southwestern Africa. AB - OBJECTIVES: We investigated the frequency distribution and haplotype diversity of human African trypanosomiasis (HAT) resistance and lactase persistence (LP) variants in populations from the Angolan Namib to trace the spread of these genetic adaptations into southwestern Africa. MATERIALS AND METHODS: We resequenced two fragments of the LCT enhancer and the APOL1 gene and genotyped flanking short tandem repeat loci in six groups with different subsistence traditions living in the Angolan Namib, and in a comparative dataset including other populations from Africa and Europe. LP in the Angolan Namib is represented by the -14010*C allele, which is associated with a predominant haplotype that is shared with other southern and eastern African populations. While LP was found to be more frequent in foragers than in pastoralists, the frequencies of the two APOL1 variants associated with HAT-resistance (G1 and G2) did not differ between the two groups. The G1 allele is mostly associated with a single widespread haplotype. The G2 allele is linked to several haplotypes that are molecularly related to haplotypes found in other African Bantu-speaking populations. The putatively archaic G3 variant displayed more intra-allelic diversity in Africa than in Europe. DISCUSSION: The LP adaptation was carried to southern Africa by non-Bantu speaking pastoralists from eastern Africa, but an obvious link between its presence in southern Angola and groups speaking languages of the Khoe-Kwadi family, as previously found in other areas, could not be confirmed. The presence of APOL1 variants G1 and G2 is linked to the Bantu expansions. Our results suggest that the G3 variant was retained in modern humans by incomplete lineage sorting. PMID- 27402287 TI - Editorial introduction. PMID- 27402286 TI - Diuretics prescribing in chronic kidney disease patients: physician assessment versus bioimpedence spectroscopy. AB - INTRODUCTION: The relationship between hypertension and fluid overload in pre dialysis CKD patients need to be elucidated. Current study aimed to find relationship between fluid overload and hypertension along with prescribed diuretic therapy using bioimpedance spectroscopy (BIS). METHODOLOGY: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS. RESULTS: A total of 312 CKD patients with mean eGFR 24.5 +/- 11.2 ml/min/1.73 m2 were enrolled. Based on OH value >=7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics. CONCLUSION: BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients. PMID- 27402288 TI - Toll-like receptors signaling: A complex network for NF-kappaB activation in B cell lymphoid malignancies. AB - Malignancies of mature B cells are quite distinctive in originating from well differentiated cells. Hence, it is not paradoxical that, similar to their normal counterparts, most mature B cell lymphoma subtypes are critically dependent on microenvironmental cues. Such external signals are sensed by various receptors present on the malignant cells, including the Toll-like receptors (TLRs), eliciting a range of cellular responses, including proliferation but also anergy and apoptosis, often with disease-specific patterns. Critically, the TLR signaling pathways are intertwined with other receptor pathways in malignant B cells, most notably the B-cell receptor pathway, and converge on NF-kappaB, leading to its activation. In the present review, we summarize the literature on TLR expression and functionality and its impact on NF-kappaB activation in different B cell malignancies including chronic lymphocytic leukemia where TLR9 induces activation, cell proliferation and chemoresistance in a proportion of patients while apoptosis can be induced in others. Additionally, we also discuss the therapeutic potential of strategies targeting TLR signaling in lymphoma. PMID- 27402289 TI - Grape tannin catechin and ethanol fluidify oral membrane mimics containing moderate amounts of cholesterol: Implications on wine tasting? AB - Wine tasting results in interactions of tannin-ethanol solutions with proteins and lipids of the oral cavity. Among the various feelings perceived during tasting, astringency and bitterness most probably result in binding events with saliva proteins, lipids and receptors. In this work, we monitored the conjugated effect of the grape polyphenol catechin and ethanol on lipid membranes mimicking the different degrees of keratinization of oral cavity surfaces by varying the amount of cholesterol present in membranes. Both catechin and ethanol fluidify the membranes as evidenced by solid-state 2H NMR of perdeuterated lipids. The effect is however depending on the cholesterol proportion and may be very important and cumulative in the absence of cholesterol or presence of 18 mol % cholesterol. For 40 mol % cholesterol, mimicking highly keratinized membranes, both ethanol and catechin can no longer affect membrane dynamics. These observations can be accounted for by phase diagrams of lipid-cholesterol mixtures and the role played by membrane defects for insertion of tannins and ethanol when several phases coexist. These findings suggest that the behavior of oral membranes in contact with wine should be different depending of their cholesterol content. Astringency and bitterness could be then affected; the former because of a potential competition between the tannin-lipid and the tannin-saliva protein interaction, and the latter because of a possible fluidity modification of membranes containing taste receptors. The lipids that have been up to now weakly considered in oenology may be become a new actor in the issue of wine tasting. PMID- 27402290 TI - Formation of a thermally stable bilayer of coadsorbed intact and deprotonated thymine exploiting the surface corrugation of rutile TiO2(110). AB - The adsorption of thymine, a pyrimidine based nucleobase, was studied on the (110) termination of rutile titanium dioxide in order to understand the thermal stability and gross structural parameters of the interaction between a strongly polar adsorbate and a highly corrugated transition metal oxide surface. Near-edge X-ray absorption fine structure (NEXAFS), X-ray photoelectron spectroscopy (XPS), temperature programmed XPS and temperature programmed desorption indicated the growth of a room temperature stable bilayer, which could only be removed by annealing to 450 K. The remaining first layer was remarkably robust, surviving annealing up to 550 K before undergoing N-H bond scission. The comparison to XPS of a sub-monolayer exposure of 1-methyluracil shows that the origin of the room temperature stable bilayer is not intermolecular interactions. This discovery, alongside the deprotonation of one of the first layer's pyrimidinic nitrogen atoms at room temperature, suggests that the thymine molecules in the first layer bind to the undercoordinated surface Ti atoms, and the second layer thymine molecules coordinate with the bridging oxygen atoms which protrude above the Ti surface plane on the (110) surface. The NEXAFS results indicate an almost upright orientation of the molecules in both layers, with a 30 +/- 10 degrees tilt away from the surface normal. PMID- 27402291 TI - Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus. AB - Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 +/- 0.9 vs.12.5 +/- 0.6, p < 0.001). The red cell distribution width was positively associated with albuminuria creatinine ratio (r = 0.567, p < 0.001). Multiple logistic regressions showed that red cell distribution width was still associated with early-stage renal injury after adjusting for many other potential cofounders. Compared with the first quartile, the risk ratio of the second, the third and the fourth quartile were 1.38 (95%CI: 1.06-1.80), 1.57 (95%CI: 1.21 2.97), 2.71 (95%CI: 2.08-3.54), respectively. Besides, systolic blood pressure, estimated glomerular filtration rate, uric acid and blood urea nitrogen were also significantly associated with renal injury in gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices. PMID- 27402292 TI - Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart. AB - Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 MUg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max, suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca2+ channel [(+/-)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), beta-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia. PMID- 27402293 TI - A Smartphone App for Increasing Live Organ Donation. AB - The incidence of live donor transplantation has declined over the past decade, and waitlisted candidates report substantial barriers to identifying a live donor. Since asking someone to donate feels awkward and unfamiliar, candidates are hesitant to ask directly and may be more comfortable with a passive approach. In collaboration with Facebook leadership (Facebook Inc., Menlo Park, CA), we developed a mobile application-an app-that enables waitlisted candidates to create a Facebook post about their experience with organ failure and their need for a live donor. We conducted a single-center prospective cohort study of 54 adult kidney-only and liver-only waitlisted candidates using the Facebook app. Cox proportional hazards models were used to describe donor referral on behalf of candidates using the app compared with matched controls. The majority of candidates who used the app reported it to be "good" or "excellent" with regard to the installation process (82.9%), readability (88.6%), simplicity (70.6%), clarity (87.5%) and the information provided (85.3%). Compared with controls, candidates using the Facebook app were 2.43 6.6117.98 times more likely to have a donor come forward on their behalf (p < 0.001). The Facebook app is an easy-to use instrument that enables waitlisted candidates to passively communicate with their social network about their need for a live donor. PMID- 27402294 TI - [Hypertension and pregnancy. Expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology]. AB - High blood pressure in pregnancy remains, by its complications, the leading cause of morbidity and maternal and fetal mortality. The frequency (5 to 10% of pregnancies) and the potential severity of this disease, both for mother and child, encourage to standardize and to optimize our medical practices. This is the main objective of this work. If the short-term complications for the mother and child are well known, long-term ones for the mother beginning to be better identified (in particular, the risk of recurrence in a subsequent pregnancy, the risk of chronic hypertension and the increased risk of cardiovascular events). The occurrence of hypertension during pregnancy disturbs the "classic" organization of care. Several health professionals are involved, the general practitioner, obstetrician, gynecologist, midwife, cardiologist, nephrologist... There is not always a care coordinator and decisions are sometimes taken with delay. These data encouraged the French Society of Hypertension to write a consensus offering easy and efficient recommendations. Educate women and all health professionals to hypertension and its management, in line with current scientific data, is one of the major challenges of this consensus. PMID- 27402295 TI - [Hypertension in pregnancy and future maternal health]. AB - Preeclampsia is a specific risk factor chronic of hypertension, of coronary events (Ray et al., 2005), of stroke (Brown et al., 2006), of chronic renal failure (Kattah and Garovic, 2005; McDonald et al., 2003; Williams, 2003) and a specific risk factor of cardio-cerebrovascular mortality (Magnussen et al., 2009). According to Magnusson et al. (2009), the relative long-term risk of developing hypertension is multiplied by 4; the risk of diabetes and metabolic syndrome multiplied by 3; the risk of coronary heart disease and stroke multiplied by 2. Cardiovascular risk is particularly important when pregnancy was complicated by maternal and fetal events or occurring precociously (Williams, 2003; Newstead et al., 2007). Early PE is associated with a relative risk of death by 7 of CV disease. Several pathophysiological factors are common between CV disease and preeclampsia: endothelial dysfunction, hypertension, obesity, insulin resistance, dyslipidemia and CV heredity. Metabolic syndrome could be the link between preeclampsia and CV disease. Hypertension in pregnancy and preeclampsia could unmask metabolic syndrome "latent" existing (Silva et al., 2008). Recently, scientific societies have published guidelines dedicated to cardiovascular risk in women and for the prevention of stroke in women. They recognize hypertension in pregnancy and preeclampsia as specific emerging risk (Mosca et al., 2011; European Society of Gynecology et al., 2011; Bushnell et al., 2014). Paradoxically, information and prevention of these women at risk is insufficient to ignorance and lack of awareness among health professionals (Brown et al., 2013). The education of women has become a major issue of prevention, developing specific consultation after delivery, encouraging them to optimize their lifestyle with a coordinated follow-up (Newstead et al., 2007; Mosca et al., 2011; European Society of Gynecology et al., 2011; Bushnell et al., 2014, Harskamp and Zeeman, 2007). In the end, the implementation of structured care pathway, further monitoring of these women, aims to improve the practices of health professionals (Manten et al., 2007; Adams et al., 2014; Mounier-Vehier et al., 2014). PMID- 27402296 TI - New neurogenic lipoic-based hybrids as innovative Alzheimer's drugs with sigma-1 agonism and beta-secretase inhibition. AB - BACKGROUND: Neurogenic agents emerge as innovative drugs for the treatment of Alzheimer's disease (AD), whose pathological complexity suggests strengthening research in the multi-target directed ligands strategy. RESULTS: By combining the lipoic acid structure with N-benzylpiperidine or N,N-dibenzyl(N-methyl)amine fragments, new multi-target directed ligands were obtained that act at three relevant targets in AD: sigma-1 receptor (sigma1R), beta-secretase-1 (BACE1) and acetylcholinesterase (AChE). Moreover, they show potent neurogenic properties, good antioxidant capacity and favorable CNS permeability. Molecular modeling studies on AChE, sigma1R and BACE1 highlight relevant drug-protein interactions that may contribute to the development of new disease-modifying drugs. CONCLUSION: New lipoic-based sigma1 agonists endowed with neurogenic, antioxidant, cholinergic and amyloid beta-peptide-reducing properties have been discovered for the potential treatment of AD. PMID- 27402297 TI - beta-Amyloid-acetylcholine molecular interaction: new role of cholinergic mediators in anti-Alzheimer therapy? AB - BACKGROUND: For long time Alzheimer's disease has been attributed to a cholinergic deficit. More recently, it has been considered dependent on the accumulation of the amyloid beta peptide (Abeta), which promotes neuronal loss and impairs neuronal function. Results/methodology: In the present study, using biophysical and biochemical experiments we tested the hypothesis that in addition to its role as a neurotransmitter, acetylcholine may exert its action as an anti Alzheimer agent through a direct interaction with Abeta. CONCLUSION: Our data provide evidence that acetylcholine favors the soluble peptide conformation and exerts a neuroprotective effect against the neuroinflammatory and toxic effects of Abeta. The present paper paves the way toward the development of new polyfunctional anti-Alzheimer therapeutics capable of intervening on both the cholinergic transmission and the Abeta aggregation. PMID- 27402298 TI - Characterization of chemical features of potent myeloperoxidase inhibitors. AB - BACKGROUND: Despite its important role in the immune system, myeloperoxidase (MPO) is implicated in a wide range of inflammatory syndromes due to its oxidative product HOCl. The oxidative damages caused by MPO make it a new target for developing promising anti-inflammatory agents. In this paper, we tried to understand the mechanism of MPO inhibition in order to facilitate the drug design, to develop more accurate virtual tests and to understand the structure activity relationship. RESULTS: Based on docking experiments, kinetic studies and in vitro tests, it is determined that a potent MPO inhibitor must possess an oxidizable group in addition to a high affinity with the active site. At last, a new hit was found in this work namely 4-(3-hydroxy-phenoxy)-butylamine (5) that has IC50 of 86 nM. CONCLUSION: Hydroxy-phenoxy alkylamine derivatives were found to be promising MPO inhibitors and they may represent an important starting point in the development of more potent MPO inhibitors. PMID- 27402299 TI - Biocompatibility of polymer-infiltrated-ceramic-network (PICN) materials with Human Gingival Fibroblasts (HGFs). AB - OBJECTIVES: Polymer-infiltrated-ceramic-network (PICN) materials constitute an innovative class of CAD-CAM materials offering promising perspectives in prosthodontics, but no data are available in the literature regarding their biological properties. The objective of the present study was to evaluate the in vitro biocompatibility of PICNs with human gingival fibroblasts (HGFs) in comparison with materials typically used for implant prostheses and abutments. METHODS: HGF attachment, proliferation and spreading on discs made of PICN, grade V titanium (Ti), yttrium zirconia (Zi), lithium disilicate glass-ceramic (eM) and polytetrafluoroethylene (negative control), were evaluated using a specific insert-based culture system (IBS-R). Sample surface properties were characterized by XPS, contact angle measurement, profilometry and SEM. RESULTS: Ti and Zi gave the best results regarding HGF viability, morphology, number and coverage increase with time in comparison with the negative control, while PICN and eM gave intermediate results, cell spreading being comparable for PICN, Ti, Zi and eM. Despite the presence of polymers and their related hydrophobicity, PICN exhibited comparable results to glass-ceramic materials, which could be explained by the mode of polymerization of the monomers. SIGNIFICANCE: The results of the present study confirm that the currently employed materials, i.e. Ti and Zi, can be considered to be the gold standard of materials in terms of HGF behavior, while PICN gave intermediate results comparable to eM. The impact of the present in vitro results needs to be further investigated clinically, particularly in the view of the utilization of PICNs for prostheses on bone-level implants. PMID- 27402300 TI - Frequency, type and treatment of fungal pathogens in toenail onychomycosis in the central Alpine region of South Tyrol, northern Italy - a 10-year retrospective study from 2004 to 2013. AB - Onychomycosis is one of the most common dermatological diseases, primarily caused by dermatophytes, and sometimes, also by yeast and moulds. This study aims to clarify the frequency of isolated pathogens from mycotic toenails in the reference centre of the central Alpine mountain region of South Tyrol, northern Italy. Age and gender differences, types of pathogens and initial therapy used were also investigated. This is a retrospective study from 2004 to 2013 on the files of all patients with suspected onychomycosis in whom a cultural pathogen detection was performed. A total of 1565 patients were studied (943 women; 622 men), with a median age of 55 years. Fungal pathogens could be detected by culture in 49.5%. Significantly more pathogens could be grown in men (63.8%) than in women (39.9%, P < 0.0001). The most common pathogens grown were dermatophytes (53.3%), especially T. rubrum and T. interdigitale, followed by moulds (24.7%) and yeast (22%). Therapies prescribed were topical in 64.2% and systemic in 35.8% of the cases. Topical treatment was more frequent in older patients (P < 0.05). In northern Italy, dermatophytes are the most common causative agents for onychomycosis. Fungal pathogens were more commonly found in men than in women and topical treatment was more frequent in older patients. PMID- 27402301 TI - Indolent T-cell lymphoproliferative disease of the gastrointestinal tract after treatment with adalimumab in resistant Crohn's colitis. AB - We report a case of intestinal indolent T-cell lymphoproliferative disease (TCLPD) occurring after the initiation of tumor necrosis factor-alpha (TNF-alpha) inhibitor therapy for resistant Crohn's disease. A prominent T-cell infiltrate positive for CD8, TIA-1, and T-cell receptor-betaF1 was associated with the foci of active inflammation. T-cell receptor gene clonality studies (BIOMED-2) demonstrated monoclonality. After the TNF-alpha inhibitor treatment was withdrawn, the T-cell infiltrates regressed, but 2 years later, the same monoclonal T-cell infiltrate reappeared at the only site of active inflammation. To the best of our knowledge, this report is the first to show a link between active inflammation and the TCLPD. In addition, it suggests a possible influence of the TNF-alpha inhibitor treatment on the evolution of the TCLPD. A high degree of suspicion is required in the presence of any unusual lymphoid infiltrate in inflammatory bowel disease to avoid overlooking an indolent TCLPD or misdiagnose an aggressive lymphoma. PMID- 27402303 TI - Contraction and Expansion of Stimuli-Responsive DNA Bonds in Flexible Colloidal Crystals. AB - DNA surface ligands can be used as programmable "bonds" to control the arrangement of nanoparticles into crystalline superlattices. Here, we study the intrinsic responsiveness of these DNA bonds to changes in local dielectric constant (epsilonr) as a new approach to dynamically modulate superlattice structure. Remarkably, ethanol (EtOH) addition can be used to controllably tune DNA bond length from 16 to 3 nm and to increase bond stability by >40 degrees C, while retaining long-range order and crystal habit. Interestingly, we find that these structural changes, which involve the expansion and contraction of crystals by up to 75% in volume, occur in a cooperative fashion once a critical percentage of EtOH is reached. These results provide a facile and robust approach to create stimuli-responsive lattices, to access high volume fractions, and to improve thermal stability. PMID- 27402302 TI - Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer. AB - Tumor epithelial cells undergo a morphologic shift through the process of EMT with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor beta mediates EMT programming and its phenotypic reversal to mesenchymal epithelial transition. The role of EMT in bladder cancer progression to advanced disease is poorly understood. In this study, we conducted a retrospective analysis of the EMT landscape and actin cytoskeleton remodeling in a series of human bladder cancer specimens. Immunoreactivity for E-cadherin, N-cadherin, and vimentin protein expression was performed toward establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and transforming growth factor-beta signaling effector, cofilin. Our results demonstrate that EMT induction in clinical bladder cancer specimens is significantly associated with bladder cancer progression to high-grade, invasive disease. Evaluation of expression and cellular localization of the cytoskeleton regulator cofilin revealed a significant association between overexpression of nuclear cofilin with bladder cancer progression. This study is of translational significance in defining the value of EMT signature and cytoskeletal cofilin as potential tumor markers and targetable platforms for the treatment of invasive bladder cancer. PMID- 27402304 TI - Fatal Hematoma After Removal of a Screw Driver Causing ICA Occlusion. PMID- 27402305 TI - [Study protocol concerning the determining factors of physical and psychosocial destabilisation in the elderly]. AB - OBJECTIVE: The main objective of this study is to define the factors associated with frailty and psychosocial imbalance in elderly people who live in the community. METHODS: Multicentre prospective study with a representative sample of subjects older than 75 years who live in the community in the province of Huesca (Spain). 5-year follow-up with biannual assessment. Standardised individual assessment carried out by GPs trained to assess depression, anxiety, cognitive impairment, psychotic symptoms, sarcopenia, social network, dependence for basic and instrumental activities of daily living, physical severity, risk of dependence and quality of life. Further assessment two and five years later to quantify adverse events: institutionalisation, functional impairment or mortality. Possible risk factors will be assessed: gender, age, social status, functional status, mental status and physical severity. Predictive and individual risk models will be designed in order to identify elderly people with high psychosocial frailty and destabilisation risk. CONCLUSIONS: An understanding of the possible risk factors would facilitate the identification of elderly subjects at greater risk of psychosocial frailty, thereby enabling preventive activities to be implemented aimed at reducing frailty and associated adverse events (institutionalisation, mortality, etc.). PMID- 27402306 TI - Intravascular Papillary Endothelial Hyperplasia (Masson's Tumor) of the Radial Artery: A Case Report. AB - Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson's tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodality imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH. PMID- 27402307 TI - Sub-types of nonbelieved memories reveal differential outcomes of challenges to memories. AB - Nonbelieved memories (NBMs) highlight the independence between distinct metamemorial judgements that contribute to the experience of remembering. Initial definitions of NBMs portrayed them as involving the withdrawal of belief in occurrence despite sustained recollection. While people rate belief for their NBMs as weaker than recollection, the average difference is too small to support the idea that autobiographical belief is completely withdrawn in all cases. Furthermore, autobiographical belief and recollection ratings vary considerably across NBMs. In two studies, we reanalysed data from prior studies to examine whether NBM reports reflect a single category or multiple sub-categories using cluster analytic methods. In Study 1, we identified three sub-types of NBMs. In Study 2 we incorporated the concept of belief in accuracy, and found that two of the clusters from Study 1 split into two clusters apiece. All clusters were characterised by higher recollection than belief in occurrence ratings, and clusters were differentiated by the degree of difference between these variables. In both studies the clusters were discriminated by a number of memory characteristic ratings and by reasons reported as leading to the alteration of belief. Implications for understanding the remembering of past events and predicting the creation of NBMs are discussed. PMID- 27402308 TI - Rac3 regulates cell proliferation through cell cycle pathway and predicts prognosis in lung adenocarcinoma. AB - Lung cancer is still the leading cause of malignant deaths in the world. It is of great importance to find novel functional genes for the tumorigenesis of lung cancer. We demonstrated that Rac3 could promote cell proliferation and inhibit apoptosis in lung adenocarcinoma cell line A549 previously. The aim of this study was to investigate the function and mechanism of Rac3 in lung adenocarcinoma cell lines. Immunohistochemistry staining was performed in 107 lung adenocarcinoma tissues and matched non-tumor tissues. Multivariate analysis and Kaplan-Meier analysis were used to investigate the correlation between Rac3 expression and the clinical outcomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry analysis were employed to determine the proliferative ability, cell cycle distribution, and apoptosis in H1299 and H1975 cell lines. Gene expression microarray and pathway analysis between the Rac3-siRNA group and the control group in A549 cells were performed to investigate the pathways and mechanism of Rac3 regulation. Rac3 was shown to be positively expressed in lung adenocarcinoma tissues, and the expression of Rac3 associates with longer survival in lung adenocarcinoma patients. Silencing of Rac3 significantly induced cell growth inhibition, colony formation decrease, cell cycle arrest, and apoptosis of lung adenocarcinoma cell lines, which accompanied by obvious downregulation of CCND1, MYC, and TFDP1 of cell cycle pathway involving in the tumorigenesis of lung adenocarcinoma based on the gene expression microarray. In conclusion, these findings suggest that Rac3 has the potential of being a therapeutic target for lung adenocarcinoma. PMID- 27402309 TI - Sleep quality and daytime sleepiness in patients with COPD and asthma. AB - INTRODUCTION: Nocturnal symptoms are common and important in both asthma and COPD but the relationship between sleep quality and diseases' characteristics has not been fully studied. OBJECTIVE: To compare sleep quality and daytime sleepiness in asthma and COPD patients and to explore its relation to diseases' characteristics. METHODS: In this cross-sectional study, we examined 217 consecutive asthma and COPD patients who underwent pulmonary function tests at The Center for Pathophysiology of Breathing and Sleep Medicine of The Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia between July 2014 and January 2015. All patients completed Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). RESULTS: Study included 117 patients with asthma, 100 patients with COPD, and 102 healthy controls. There was no difference in PSQI and ESS between patients with asthma and COPD (4.9 +/- 3.9 vs 5.8 +/- 4.3, P = .09 and 4.8 +/- 3.4 vs 4.7 +/- 3.6, P = .69, respectively). PSQI and ESS did not correlate with lung function parameters. Patients with uncontrolled asthma had higher PSQI scores (uncontrolled 7.0 +/- 3.7 vs partially controlled 4.6 +/- 3.1 vs controlled 3.2 +/- 3.7, P < .001). PSQI scores were higher in COPD group D and B compared to A and C (group D 6.9 +/-4.6 vs B 6.8 +/- 4.1 vs A 2.9 +/- 1.3 vs C 3.1 +/- 3.9, P < .001). Compared to asthma, COPD patients had longer sleep latency and used sleep regulating medications more often. CONCLUSIONS: There is no difference in sleep quality and level of daytime sleepiness between patients with asthma and COPD. Poor sleep quality is related to level of asthma control and is associated with COPD groups B and D. PMID- 27402310 TI - [Humanization of perinatal care. A social demand and professional challenge]. PMID- 27402311 TI - Why Cortical Neurons Cannot Divide, and Why Do They Usually Die in the Attempt? AB - Cortical neurons are prime examples of terminally differentiated, postmitotic cells. However, under experimental or pathological conditions, they can re-enter the cell cycle and replicate DNA but are unable to divide, dying by apoptosis or becoming either polyploid or aneuploid. Any cellular state that depends on the action of genes and their products can be reverted or bypassed by spontaneous or induced mutations, yet there are currently no reports of dividing cortical neurons. Thus, it seems unlikely that the remarkably stable postmitotic condition of cortical neurons depends on specific gene functions. This Review summarizes evidence that the postmitotic state of cortical neurons depends on the high stability of its underlying nuclear structure that results from an entropy-driven process aimed at dissipating the intrinsic structural stress present in chromosomal DNA in such a way that the structural stability of the neuronal nucleus becomes an insurmountable energy barrier for karyokinesis and mitosis. From this perspective, the integral properties of the nuclear higher order structure in neurons provide an explanation not only for why cortical neurons cannot divide but also for why they usually die if they happen to replicate their DNA. (c) 2016 Wiley Periodicals, Inc. PMID- 27402312 TI - TB biomarkers, TB correlates and human challenge models: New tools for improving assessment of new TB vaccines. AB - The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Biomarkers and Correlates, and Human Challenge Models. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30]. PMID- 27402313 TI - Advocacy, partnership and political commitment for TB vaccine research. AB - The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Advancing the Pipeline: A Vision for the Next Decade, Engaging the BRICS: Basic Research to Manufacturing, and Regulatory and Access Issues for New TB Vaccines. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30]. PMID- 27402314 TI - Erratum to: Electrospun silk fibroin mat enhances tendon-bone healing in a rabbit extra-articular model. PMID- 27402315 TI - A Hearing Screening Program for Children in Primary Schools in Tajikistan: A Telemedicine Model. AB - BACKGROUND According to the guidelines of the European Scientific Consensus on Hearing (European Federation of Audiology Societies 'EFAS' Congress, June 2011, Warsaw, Poland), the detection and treatment of communication disorders in early school-age children is of the highest importance. This objective was adopted by the Polish president of the EFAS Council from the second half of 2011; as a result, pilot programs on children's hearing screening were initiated in various European countries. This paper reports data from a pilot program in Dushanbe, Tajikistan. MATERIAL AND METHODS We randomly selected 143 children from 2 primary schools. Each child was assessed by pure tone audiometry and 2 questionnaires (dedicated to parents and children). The study allowed the validation of: (i) hearing screening procedures in young children, and (ii) data collection via a telemedicine model. RESULTS Hearing impairments were identified in 34 cases (23.7%) with a 50% ratio between unilateral and bilateral losses. We found a higher incidence of hearing impairment in children than that reported in previous Polish studies. CONCLUSIONS The data from the present study suggest that it is possible to use a telemedicine model to assess the hearing status of children and to provide a long-distance expert assistance. The latter is very important for rural areas without specialized medical services. PMID- 27402316 TI - A synthetic C16 omega-hydroxyphytoceramide improves skin barrier functions from diversely perturbed epidermal conditions. AB - Omega-hydroxyceramides (omega-OH-Cer) play a crucial role in maintaining the integrity of skin barrier. omega-OH-Cer are the primary lipid constituents of the corneocyte lipid envelope (CLE) covalently attached to the outer surface of the cornified envelope linked to involucrin to become bound form lipids in stratum corneum (SC). CLE becomes a hydrophobic impermeable layer of matured corneocyte preventing loss of natural moisturizing factor inside the corneocytes. More importantly, CLE may also play an important role in the formation of proper orientation of intercellular lipid lamellar structure by interdigitating with the intercellular lipids in a comb-like fashion. Abnormal barrier conditions associated with atopic dermatitis but also UVB-irradiated skins are known to have lowered level of bound lipids, especially omega-OH-Cer, which indicate that omega OH-Cer play an important role in maintaining the integrity of skin barrier. In this study, protective effects of a novel synthetic C16 omega hydroxyphytoceramides (omega-OH-phytoceramide) on skin barrier function were investigated. Epidermal barrier disruption was induced by UVB irradiation, tape stripping in hairless mouse and human skin. Protective effect of damaged epidermis was evaluated using the measurement of transepidermal water loss and cohesion of SC. Increased keratinocyte differentiation was verified using cultured keratinocyte through western blot. Results clearly demonstrated that a synthetic C16 omega-OH-phytoceramide enhanced the integrity of SC and accelerated the recovery of damaged skin barrier function by stimulating differentiation process. In a conclusion, a synthetic C16 omega-OH-phytoceramide treatment improved epidermal homeostasis in several disrupted conditions. PMID- 27402317 TI - Scientists of Tomorrow at the Frontiers of Cardiovascular Biology 2016 in Florence: translating basic science into clinical practice is the next frontier. PMID- 27402318 TI - Salvage pathways in heart rejuvenation. PMID- 27402319 TI - Virtual issue: focus on cardiovascular protection. PMID- 27402321 TI - Autoimmune-like drug-induced liver injury: a review and update for the clinician. AB - INTRODUCTION: Autoimmune-like drug-induced liver injury (DI-AIH) is a rare but serious event with a growing body of scientific evidence and a fair degree of uncertainty. AREAS COVERED: This review covers the definition, pathophysiology, treatment and patient-centered outcomes of DI-AIH and presents up-to-date information on the most commonly implicated drugs. EXPERT OPINION: A high degree of clinical suspicion is required for the diagnosis of DI-AIH. This diagnosis should be considered in any patient with either acute or chronic elevations in liver-associated enzymes. Prevalence rates exceed 15% based on large international registry data. Autoantibodies, while common, are neither specific nor diagnostic of DI-AIH. Histology may be helpful in describing subtle differences between DI-AIH and de novo idiopathic autoimmune hepatitis (iAIH), but oftentimes the two are indistinguishable histologically. Alpha-methyldopa, fibrates, hydralazine, minocycline, nitrofurantoin, HMG-CoA reductase inhibitors (statins), iplimumab and tumor necrosis factor alpha antagonists are the most commonly associated drugs with DI-AIH. Complete recovery of liver injury is most often seen with DI-AIH, however, cases of prolonged injury may occur and may require treatment with immunosuppressive therapy. Relapse following cessation of corticosteroids for suspected DI-AIH should prompt reconsideration of the diagnosis and further exploration into possible iAIH. PMID- 27402320 TI - Management of splenic and pancreatic trauma. AB - The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately beneath the ribs. Injury to the more deeply placed pancreas is classically characterized by discordance between the severity of pancreatic injury and its initial clinical expression. For the patient who presents with hemorrhagic shock and ultrasound evidence of major hemoperitoneum, urgent "damage control" laparotomy is essential; if splenic injury is the cause, prompt "hemostatic" splenectomy should be performed. Direct pancreatic injury is rarely the cause of major hemorrhage unless a major neighboring vessel is injured, but if there is destruction of the pancreatic head, a two-stage pancreatoduodenectomy (PD) may be indicated. At open laparotomy when the patient's hemodynamic status can be stabilized, it may be possible to control splenic bleeding without splenectomy; it is always essential to search for injury to the pancreatic duct and/or the adjacent duodenum. Pancreatic contusion without ductal rupture is usually treated by drain placement adjacent to the injury; ductal injuries of the pancreatic body or tail are treated by resection (distal pancreatectomy with or without splenectomy), with generally benign consequences. For injuries of the pancreatic head with pancreatic duct disruption, wide drainage is usually performed because emergency PD is a complex gesture prone to poor results. Postoperatively, the placement of a ductal stent by endoscopic retrograde catheterization may be decided, while management of an isolated pancreatic fistula is often straightforward. Non-operative management is the rule for the trauma victim who is hemodynamically stable. In addition to the clinical examination and conventional laboratory tests, investigations should include an abdominothoracic CT scan with contrast injection, allowing identification of all traumatized organs and assessment of the severity of injury. In this context, non operative management (NOM) has gradually become the standard as long as the patient remains hemodynamically stable and there is no suspicion of injury to hollow viscera, with the patient being carefully monitored on a surgical service. The development of arteriography with splenic artery embolization has increased the rate of splenic salvage; this can be performed electively based on specific indications (blush on CT, pseudoaneurysm, arteriovenous fistula), and may also be considered for severe splenic injury, abundant hemoperitoneum, or severe polytrauma. For pancreatic injury, in addition to CT scan, magnetic resonance pancreatography (MRCP) or even endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to identify a ductal rupture. If the pancreatic duct is intact, laboratory and CT imaging surveillance is performed just as for splenic injury. In case of pancreatic ductal injury, ERCP stenting can be considered. However, if this is unsuccessful, the therapeutic decision can be difficult: while NOM can still be successful, complications may arise that are difficult to treat while distal pancreatectomy, although initially more agressive may avoid these complications if performed early. PMID- 27402322 TI - Ferrocene-quinoxaline Y-shaped chromophores as fascinating second-order NLO building blocks for long lasting highly active SHG polymeric films. AB - The first example of a Y-shaped ferrocene quinoxaline derivative with a surprisingly high and stable second harmonic generation (SHG) response in composite polymeric films is reported. The interesting quadratic hyperpolarizability values of different substituted Y-shaped chromophores are also investigated in solution by the EFISH technique. PMID- 27402323 TI - Cigarette Taxes, Smoking-and Exercise? AB - This research provides the first in-depth analysis of the effect that increased cigarette taxes have on exercise behavior. Smoking may diminish the ability to exercise; individuals may also use exercise to compensate for the harmful health effects of smoking or to avoid gaining weight if they cut back. Our conceptual model highlights these and several other avenues for effect and reveals that the predicted effect of cigarette costs on exercise behavior is theoretically ambiguous. To investigate the relationship empirically, 1994-2012 data from the behavioral risk factor surveillance system are combined with state level cigarette tax rates and other state level variables. Several measures of both smoking and exercise behavior are created and estimated in reduced form models. Our results suggest that both smoking and exercise are reduced by cigarette taxes. However, the effects on exercise may be more complicated as we find that certain groups, such as young adults or those who have recently quit smoking, are affected differently. Our analyses also show that the responsiveness of both smoking and exercise behavior to cigarette costs is much smaller in the 2000s, an era of high-tax increases. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27402324 TI - Acrylate and methacrylate contact allergy and allergic contact disease: a 13-year review. AB - BACKGROUND: (Meth)acrylates are important causes of contact allergy and allergic contact disease, such as dermatitis and stomatitis, with new and emerging sources resulting in changing clinical presentations. OBJECTIVES: To identify the (meth)acrylates that most commonly cause allergic contact disease, highlight their usefulness for screening, and examine their relationship with occupational and clinical data. METHODS: A retrospective review of results from patch tests performed between July 2002 and September 2015, in one tertiary Cutaneous Allergy Unit, was performed RESULTS: A series of 28 (meth)acrylates was applied to 475 patients. Results were positive in 52 cases, with occupational sources being identified in 24. Industrial exposures and acrylic nails were responsible for 13 and 10 cases, respectively, with wound dressings being implicated in 7. We found that four individual (meth)acrylates (2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, bisphenol A glycerolate dimethacrylate, and ethyl acrylate), if used as a screening tool, could have identified 47 (90.4%) of our positive cases. CONCLUSIONS: Our 13-year experience indicates a changing landscape of (meth)acrylate contact allergy and allergic contact disease, with an observed shift in exposures away from manufacturing and towards acrylic nail sources. Wound dressings are highlighted as emerging sources of sensitization. Larger studies are required to establish the sensitivity and specificity of the four (meth)acrylates proposed for potential screening. PMID- 27402326 TI - EXPRESSION AND EFFECTS OF MUTANT Bombyx mori ACETYLCHOLINESTRASE1 IN BmN CELLS. AB - The main mechanism of toxicity of organophosphate (OP) and carbamate (CB) insecticides is their irreversible binding and inhibition of acetylcholinestrase (AChE), encoded by ace1 (acetylcholinestrase gene 1), leading to eventual death of insects. Mutations in AChE may significantly reduce insects susceptibility to these pesticides. Bombyx mori is an important beneficial insect, and no OP- or CB resistant strains have been generated. In this study, wild-type ace1 (wace1) and mutant ace1 (mace1) were introduced into BmN cells, confirmed by screening and identification. The expression of wace1 and mace1 in the cells was confirmed by Western blot and their expression levels were about 21-fold higher than the endogenous ace1 level. The activities of AChE in wace1 and mace1 transgenic cells were 10.6 and 20.2% higher compared to control cells, respectively. mace1 transgenic cells had higher remaining activity than wace1 transgenic cells under the treatment of physostigmine (a reversible cholinesterase inhibitor) and phoxim (an OP acaricide). The results showed that ace1 transgene can significantly improve ace1 expression, and ace1 mutation at a specific site can reduce the sensitivity to AChE inhibitors. Our study provides a new direction for the exploration of the relationship between AChE mutations and drug resistance. PMID- 27402327 TI - John Watt Robertson. PMID- 27402325 TI - Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids. AB - An ability to develop sequence-defined synthetic polymers that both mimic lipid amphiphilicity for self-assembly of highly stable membrane-mimetic 2D nanomaterials and exhibit protein-like functionality would revolutionize the development of biomimetic membranes. Here we report the assembly of lipid-like peptoids into highly stable, crystalline, free-standing and self-repairing membrane-mimetic 2D nanomaterials through a facile crystallization process. Both experimental and molecular dynamics simulation results show that peptoids assemble into membranes through an anisotropic formation process. We further demonstrated the use of peptoid membranes as a robust platform to incorporate and pattern functional objects through large side-chain diversity and/or co crystallization approaches. Similar to lipid membranes, peptoid membranes exhibit changes in thickness upon exposure to external stimuli; they can coat surfaces in single layers and self-repair. We anticipate that this new class of membrane mimetic 2D nanomaterials will provide a robust matrix for development of biomimetic membranes tailored to specific applications. PMID- 27402328 TI - Vertical partitioning of freshwater bacterioplankton community in a deep mesotrophic lake with a fully oxygenated hypolimnion (Lake Biwa, Japan). AB - In freshwater microbial ecology, extensive studies are attempting to characterize the vast majority of uncultivated bacterioplankton taxa. However, these studies mainly focus on the epilimnion and little is known regarding the bacterioplankton inhabiting the hypolimnion of deep holomictic lakes, despite its biogeochemical importance. In this study, we investigated the bacterioplankton community composition in a deep freshwater lake with a fully oxygenated hypolimnion (Lake Biwa, Japan) using high-throughput 16S rRNA gene amplicon sequencing. Sampling at a pelagic site over 15 months throughout the water column revealed that the community composition in the hypolimnion was significantly different from that in the epilimnion. The bacterial community in the hypolimnion was composed of groups dominating in the whole water layer (e.g., bacI-A1 and acI-B1) and groups that were hypolimnion habitat specialists. Among the hypolimnion specialists, members of Chloroflexi and Planctomycetes were highly represented (e.g., CL500-11, CL500 15 and CL500-37), followed by members of Acidobacteria, Chlorobi and nitrifiers (e.g., Ca. Nitrosoarchaeum, Nitrosospira and Nitrospira). This study identified the number of previously understudied taxa dominating the deep aerobic freshwater habitat, suggesting that the biogeochemical cycling there is driven by the microbial community that are different from that in the epilimnion. PMID- 27402329 TI - [Experience with the radiosurgical treatment of brain metastases]. AB - OBJECTIVE: To analyse the survival rate of a cohort of patients with intracranial metastases treated with radiosurgery, and to determine the factors that influence the results. PATIENTS AND METHOD: Retrospective analysis performed on a cohort of 126 patients undergoing radiosurgery for brain metastases. Patients treated with surgery before or after radiosurgery were excluded. Survival is analysed based on clinical (age, sex, primary tumour), radiological (number, location and volume of lesions), and radiotherapy factors (treatment dose, holocraneal radiation). Univariate and multivariate analyses were performed to determine significant prognostic factors. RESULTS: A total of 225 brain metastases in 126 patients, with a mean age of 59.8+/-11.6years, were treated between February 2008 and April 2015. The mean survival was 8.2 months. The overall survival rates at 6months, 1year, and 2years were 60.3%, 31.5%, and 12.8%, respectively. Lung (59.5%) and breast (14.3) were the most common primary tumours, and the most common site for metastases was the cerebral hemisphere (77%) and the average volume was 10.35 cc (0.2-43.5). Significant survival factors were: age under 60 (P=.046), female (P<.001), breast cancer (P<.001), KPS >80 (P=.001), SIR6 >5 (P=.031), and GPA >=2.5 (P=.003). CONCLUSIONS: Radiosurgery is an appropriate technique for the treatment of brain metastases, and the main prognostic factors include being age under 65, female, breast cancer, and good scores on Karnofsky, SIR, and GPA scales. PMID- 27402330 TI - Early Life Antibiotic Exposure and Weight Development in Children. AB - OBJECTIVE: To examine the timing, frequency, and type of antibiotic exposure during the first 10 years of life in association with (over)weight across this period in a cohort of 979 children. STUDY DESIGN: Within the Child, Parents and Health: Lifestyle and Genetic Constitution Birth Cohort Study, antibiotic exposure record was obtained from general practitioners. Anthropometric outcomes (age- and sex-standardized body mass index, weight and height z-scores, and overweight) were measured repeatedly at 7 time points during the first 10 years of life. Generalized estimating equations method was used for statistical analysis. RESULTS: After adjusting for confounding factors, children exposed to one course of antibiotics compared with none in the first 6 months of life had increased weight- (adjusted generalized estimating equations estimates [adjbeta] 0.24; 95% CI 0.03-0.44) and height (adjbeta 0.23; 95% CI 0.0002-0.46) z-scores; exposure to >=2 courses during the second year of life was associated with both increased weight (adjbeta 0.34; 95% CI 0.07-0.60), and height z-scores (adjbeta 0.29; 95% CI -0.003 to 0.59). Exposure later in life was not associated with anthropometric outcomes. Associations with weight z-scores were mainly driven by exposure to broad- (>=2 courses: adjbeta 0.11; 95% CI 0.003-0.22) and narrow spectrum beta-lactams (1 course: adjbeta 0.18; 95% CI 0.005-0.35) during the follow-up period. Specific antibiotic used was not associated with body mass index z-scores and overweight. CONCLUSIONS: Repeated exposure to antibiotics early in life, especially beta-lactam agents, is associated with increased weight and height. If causality of obesity can be established in future studies, this further highlights the need for restrictive antibiotic use and avoidance of prescriptions when there is minimal clinical benefit. PMID- 27402331 TI - Solitary Rectal Ulcer Syndrome as a Sign of Unrecognized Hirschsprung Disease. PMID- 27402332 TI - Feasibility of a Preventive Parenting Intervention for Very Preterm Children at 18 Months Corrected Age: A Randomized Pilot Trial. AB - OBJECTIVE: To evaluate the feasibility and potential efficacy of an age appropriate additional parenting intervention for very preterm born toddlers. STUDY DESIGN: In a randomized controlled pilot study, 60 of 94 eligible very preterm born children who had received a responsive parenting intervention in their first year were randomized to usual care or the additional intervention, consisting of 4-6 home visits between 18 and 22 months' corrected gestational age (CA). Parents were supported to responsively interact during increasingly complex daily activities and play. Parental satisfaction with the intervention was evaluated with a questionnaire. At baseline and 24 months CA, parents completed the Infant Toddler Social and Emotional Assessment, the Ages and Stages Questionnaire, and the Dutch Schlichting Lexilist for receptive language. At 24 months CA, motor, and cognitive development was measured by the Bayley Scales of Infant and Toddler Development, Third Edition Dutch version, and parent-child interaction was evaluated by the Emotional Availability Scales. RESULTS: Parental compliance and satisfaction with the intervention was high. Effect sizes (after correction for baseline variables) were small for internalizing and competence behavior, receptive language, and problem solving; medium for cognitive development and parent-child interaction; and large for externalizing and dysregulation behavior and motor development. CONCLUSION: After a postdischarge intervention during the first year, an additional responsive parenting support at toddler-age is feasible and associated with positive outcomes in a broad array of parental and child outcome measures. TRIAL REGISTRATION: www.toetsingonline.nl: NL40208.018.12. PMID- 27402333 TI - Building Adolescent Sexual Health: It is not Your Mother's Birds and Bees. PMID- 27402334 TI - Clinical Considerations to Enhance the Efficacy of Cognitive Behavioral Treatments for OCD Including Parental Involvement. PMID- 27402336 TI - Secretome analysis of virulent Pyrenophora teres f. teres isolates. AB - Pyrenophora teres f. teres (Ptt) causes net form net blotch disease of barley, partially by producing necrosis-inducing proteins. The protein profiles of the culture filtrates of 28 virulent isolates were compared by a combination of 2DE and 1D-PAGE with 105 spots and 51 bands chosen for analysis by liquid chromatography electrospray ionization tandem mass spectrometry. A total of 259 individual proteins were identified with 63 of these proteins being common to the selected virulent isolates. Ptt secretes a broad spectrum of proteins including cell wall degrading enzymes; virulence factors and effectors; proteins associated with fungal pathogenesis and development; and proteins related to oxidation reduction processes. Potential virulence factors and effectors identified included proteins with glucosidase activity, ricin B and concanavalin A-like lectins, glucanases, spherulin, cutinase, pectin lyase, leucine-rich repeat protein, and ceratoplatanin. Small proteins with unknown function but cysteine rich, common to effectors, were also identified. Differences in the secretion profile of the Ptt isolates have also provided important insight into the different mechanisms contributing to virulence and the development of net form net blotch symptoms. PMID- 27402337 TI - A national survey of facilities for complainants of sexual assault. AB - In 2006, a national survey demonstrated wide disparities in services offered to sexual assault complainants in the UK, most marked between sexual assault referral centres and non-sexual assault referral centres (police victim examination suites). With national standards introduced in 2009 and the expansion of sexual assault referral centres, we aimed to evaluate the current situation. A questionnaire based on the original 2006 survey, collecting data on population covered, access, funding, personnel, medical care and clinical governance was sent to all 44 UK sexual assault referral centres open in 2012. No non-sexual assault referral centres were identified. Data were collected over six months from December 2012. Twenty-three sexual assault referral centres from England and Scotland responded (response rate 52%), but not all answered every question. All (20/20) had 24 h access for acute referrals, although one sexual assault referral centre reported 24 h opening was not always possible due to recruitment issues. Thirteen of 20 (65%) had a separate rota for under 16 s, but this was often not 24 h/day. All services (20/20) offered facilities for non-police referrals and for provision of anonymous intelligence. All sexual assault referral centres employed female examiners, 11/17 (65%) male examiners and half (10/20) forensic nurse practitioners. All (21/21) offered pregnancy testing and emergency contraception, 19/21 (90%) HIV post-exposure prophylaxis , 12/21 (57%) hepatitis B virus vaccine and 11/21 (52%) medical care for injuries on site. For follow-up care, 12/21 (57%) provided in house counselling, 10/21 (48%) sexually transmitted infection screening, 12/21 (57%) hepatitis B virus vaccination and 14/21 (67%) HIV post-exposure prophylaxis . Our survey shows improvement in services for complainants of sexual assault since 2006 with better access to forensic examinations, medical and psychological care. However, as the response rate was low and without data from non-sexual assault referral centre services, we cannot give a comprehensive national picture. Our results also show that there has been little improvement in providing sexual health screening on site or by referral and this should be addressed by sexual assault referral centres. PMID- 27402335 TI - Romidepsin induces durable responses in patients with relapsed or refractory angioimmunoblastic T-cell lymphoma. PMID- 27402338 TI - Differences in knowledge related to dental implants between patients with and without a treatment history of dental implants. AB - OBJECTIVE: This aim of this study was to investigate the differences between patients with and without a treatment history of dental implants by use of a questionnaire survey in order to determine the information that is required for patients undergoing dental implants. MATERIALS AND METHODS: The questionnaires were given to 4512 patients who visited the Tokyo Medical and Dental University Hospital for oral implants between January 2012 and December 2014, and 2972 (66%) valid questionnaires were collected. RESULTS: There were 857 patients with a treatment history of dental implants and 2115 patients without. "Preservation of an adjacent tooth" was the reason that 32% of these patients chose implant therapy, and the patients without treatment history were significantly higher than the patients with one. Significantly, more patients without a treatment history of dental implants selected the after-effects of surgery and pain after surgery as their main concerns for implant therapy compared to those with a treatment history. In the question "Pain after surgery," the patients without treatment history did not know significantly lower than the patients with one. CONCLUSIONS: Patients without a treatment history of dental implants placed more importance on the preservation of healthy teeth. Because patients, in particular those without a treatment history of dental implants, are anxious about surgery, we should provide them with more information on treatment than we already do and explain the risks of treatment to them. To keep the credence between doctors and patients, informed consent and patient education on treatment are six important concerns. PMID- 27402339 TI - Bringing next-generation diagnostics to the clinic through synthetic biology. PMID- 27402341 TI - Dissecting the U, M, S and C genomes of wild relatives of bread wheat (Aegilops spp.) into chromosomes and exploring their synteny with wheat. AB - Goat grasses (Aegilops spp.) contributed to the evolution of bread wheat and are important sources of genes and alleles for modern wheat improvement. However, their use in alien introgression breeding is hindered by poor knowledge of their genome structure and a lack of molecular tools. The analysis of large and complex genomes may be simplified by dissecting them into single chromosomes via flow cytometric sorting. In some species this is not possible due to similarities in relative DNA content among chromosomes within a karyotype. This work describes the distribution of GAA and ACG microsatellite repeats on chromosomes of the U, M, S and C genomes of Aegilops, and the use of microsatellite probes to label the chromosomes in suspension by fluorescence in situ hybridization (FISHIS). Bivariate flow cytometric analysis of chromosome DAPI fluorescence and fluorescence of FITC-labelled microsatellites made it possible to discriminate all chromosomes and sort them with negligible contamination by other chromosomes. DNA of purified chromosomes was used as a template for polymerase chain reation (PCR) using Conserved Orthologous Set (COS) markers with known positions on wheat A, B and D genomes. Wheat-Aegilops macrosyntenic comparisons using COS markers revealed significant rearrangements in the U and C genomes, while the M and S genomes exhibited structure similar to wheat. Purified chromosome fractions provided an attractive resource to investigate the structure and evolution of the Aegilops genomes, and the COS markers assigned to Aegilops chromosomes will facilitate alien gene introgression into wheat. PMID- 27402342 TI - Method of evaluation of process of red blood cell sedimentation based on photometry of droplet samples. AB - The paper focuses on research aimed at creating and testing a new approach to evaluate the processes of aggregation and sedimentation of red blood cells for purpose of its use in clinical laboratory diagnostics. The proposed method is based on photometric analysis of blood sample formed as a sessile drop. The results of clinical approbation of this method are given in the paper. Analysis of the processes occurring in the sample in the form of sessile drop during the process of blood cells sedimentation is described. The results of experimental studies to evaluate the effect of the droplet sample focusing properties on light radiation transmittance are presented. It is shown that this method significantly reduces the sample volume and provides sufficiently high sensitivity to the studied processes. PMID- 27402340 TI - TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. AB - Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid beta-peptide (Abeta) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and could result in reduced efficacy of antibody-mediated Abeta clearance. Recently, heterozygous mutations in the triggering receptor expressed on myeloid cells 2 (TREM2), a microglial gene involved in phagocytosis, were genetically linked to late onset AD Loss of TREM2 reduces the ability of microglia to engulf Abeta. We have now investigated whether loss of TREM2 affects the efficacy of immunotherapeutic approaches. We show that anti-Abeta antibodies stimulate Abeta uptake and amyloid plaque clearance in a dose-dependent manner in the presence or absence of TREM2. However, TREM2-deficient N9 microglial cell lines, macrophages as well as primary microglia showed significantly reduced uptake of antibody-bound Abeta and as a consequence reduced clearance of amyloid plaques. Titration experiments revealed that reduced efficacy of amyloid plaque clearance by Trem2 knockout cells can be compensated by elevating the concentration of therapeutic antibodies. PMID- 27402343 TI - Assessing the mean strength and variations of the time-to-time fluctuations of resting-state brain activity. AB - The time-to-time fluctuations (TTFs) of resting-state brain activity as captured by resting-state fMRI (rsfMRI) have been repeatedly shown to be informative of functional brain structures and disease-related alterations. TTFs can be characterized by the mean and the range of successive difference. The former can be measured with the mean squared successive difference (MSSD), which is mathematically similar to standard deviation; the latter can be calculated by the variability of the successive difference (VSD). The purpose of this study was to evaluate both the resting state-MSSD and VSD of rsfMRI regarding their test retest stability, sensitivity to brain state change, as well as their biological meanings. We hypothesized that MSSD and VSD are reliable in resting brain; both measures are sensitive to brain state changes such as eyes-open compared to eyes closed condition; both are predictive of age. These hypotheses were tested with three rsfMRI datasets and proven true, suggesting both MSSD and VSD as reliable and useful tools for resting-state studies. PMID- 27402345 TI - Within-population covariation between sexual reproduction and susceptibility to local parasites. AB - Evolutionary biology has yet to reconcile the ubiquity of sex with its costs relative to asexual reproduction. Here, we test the hypothesis that coevolving parasites maintain sex in their hosts. Specifically, we examined the distributions of sexual reproduction and susceptibility to local parasites within a single population of freshwater snails (Potamopyrgus antipodarum). Susceptibility to local trematode parasites (Microphallus sp.) is a relative measure of the strength of coevolutionary selection in this system. Thus, if coevolving parasites maintain sex, sexual snails should be common where susceptibility is high. We tested this prediction in a mixed population of sexual and asexual snails by measuring the susceptibility of snails from multiple sites in a lake. Consistent with the prediction, the frequency of sexual snails was tightly and positively correlated with susceptibility to local parasites. Strikingly, in just two years, asexual females increased in frequency at sites where susceptibility declined. We also found that the frequency of sexual females covaries more strongly with susceptibility than with the prevalence of Microphallus infection in the field. In linking susceptibility to the frequency of sexual hosts, our results directly implicate spatial variation in coevolutionary selection in driving the geographic mosaic of sex. PMID- 27402344 TI - Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells. AB - Inflammation in de-endothelialised arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor-alpha (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease. PMID- 27402346 TI - Implementation of the Participatory Approach for Supervisors to Increase Self Efficacy in Addressing Risk of Sick Leave of Employees: Results of a Cluster Randomized Controlled Trial. AB - Purpose To study the effectiveness of a multifaceted strategy to implement the participatory approach (PA) for supervisors to increase their self-efficacy in addressing risk of sick leave of employees. Methods Supervisors from three organizations were invited to participate. Randomization was performed at department level. Supervisors (n = 61) in the intervention departments received the implementation strategy consisting of a working group meeting, supervisor training in PA application, and optional supervisor coaching. Supervisors in the control departments (n = 55) received written information on PA. The primary outcome was supervisors' self-efficacy to apply the PA, measured at baseline and 6 months' follow-up. The number of employees with whom supervisors discussed work functioning problems or (risk of) sick leave was also assessed. Effects were tested using multilevel analyses. Results The strategy did not increase self efficacy to apply the PA. Subgroup analyses showed that self-efficacy increased for supervisors who at baseline reported to have discussed (risk of) sick leave with less than three employees during the last 6 months (B = 1.42, 95 % CI 0.34 2.50). Furthermore, the implementation strategy increased the number of employees with whom supervisors discussed work functioning problems or risk of sick leave (B = 1.26, 95 % CI 0.04-2.48). Conclusion Although the implementation strategy cannot be recommended for all supervisors, for supervisors who less frequently discuss (risk of) sick leave with employees the implementation strategy might be helpful. Trial registration NTR3733. PMID- 27402347 TI - Return to Work 2-5 Years After Stroke: A Cross Sectional Study in a Hospital Based Population. AB - Purpose To describe factors associated with RTW in patients 2-5 years after stroke. Methods Cross sectional study, including patients 2-5 years after hospitalization for a first-ever stroke, who were <65 years and had been gainfully employed before stroke. Patients completed a set of questionnaires on working status and educational level, physical functioning (Frenchay Activities Index, FAI), mental functioning (Hospital Anxiety and Depression Scale, HADS), Coping Orientations to Problems Experienced, (COPE easy) and quality of life (Short-Form(SF)-36 and EQ(Euroqol)-5D). Caregivers completed the Caregiver Strain Index (CSI). Baseline stroke characteristics were gathered retrospectively. Baseline characteristics and current health status were compared between patients who did and did not RTW by means of logistic regression analysis with odds ratios (OR) and 95 % confidence intervals (CI), adjusted for age and gender. Results Forty-six patients were included, mean age of 47.7 years (SD 9.7), mean time since stroke of 36 months (SD 11.4); 18 (39 %) had RTW. After adjusting for age and gender a shorter length of hospitalization was associated with RTW (OR 0.87; CI 0.77-0.99). Of the current health status, a lower HADS depression score (0.76; 0.63-0.92), a less avoidant coping style (1.99; 0.80-5.00), better scores on the FAI (1.13; 1.03-1.25), the mental component summary score of the SF36 (1.07; 1.01 1.13), the EQ5D (349; 3.33-36687) and the CSI (0.68; 0.50-0.92) were associated with the chance of RTW. Conclusions A minority of working patients RTW after stroke; a shorter duration of the initial hospitalization was associated with a favorable work outcome. The significant association between work status and activities, mental aspects and quality of life underlines the need to develop effective interventions supporting RTW. PMID- 27402348 TI - Circulating MicroRNAs and Life Expectancy Among Identical Twins. AB - Human life expectancy is influenced not only by longevity assurance mechanisms and disease susceptibility loci but also by the environment, gene-environment interactions, and chance. MicroRNAs (miRNAs) are a class of small noncoding RNAs closely related to genes. Circulating miRNAs have been shown as promising noninvasive biomarkers in the development of many pathophysiological conditions. However, the concentration of miRNA in the circulation may also be affected by environmental factors. We used a next-generation sequencing platform to assess the association of circulating miRNA with life expectancy, for which deaths are due to all causes independent of genes. In addition, we showed that miRNAs are present in 41-year archived plasma samples, which may be useful for both life expectancy and all-cause mortality risk assessment. Plasma miRNAs from nine identical male twins were profiled using next-generation sequencing. The average absolute difference in the minimum life expectancy was 9.68 years. Intraclass correlation coefficients were above 0.4 for 50% of miRNAs. Comparing deceased twins with their alive co-twin brothers, the concentrations were increased for 34 but decreased for 30 miRNAs. Identical twins discordant in life expectancy were dissimilar in the majority of miRNAs, suggesting that environmental factors are pivotal in miRNAs related to life expectancy. PMID- 27402350 TI - Demulsification of Redox-Active Emulsions by Chemical Oxidation. AB - This article reports the influence of redox reactions on emulsions of n-octane and an aqueous solution of a ferrocene-containing surfactant (FTMA; (11 ferrocenylundecyl)trimethylammonium bromide). Above a certain surfactant concentration, stable O/W emulsions were formed from an aqueous solution of reduced FTMA; in contrast, mixtures of n-octane and an aqueous solution of oxidized FTMA did not form emulsions at any surfactant concentration. Furthermore, adding an oxidant to the stable O/W emulsions of reduced FTMA led to coalescence of the oil (octane) droplets in the emulsions, and subsequently, the oil and water (aqueous FTMA solution) phases fully separated from the emulsions, i.e., demulsification occurred. Equilibrated interfacial tension measurements indicate that oxidation of the ferrocenyl group in FTMA brings about an increase in the interfacial tension between the octane and aqueous surfactant solution phases. From these results, we concluded that the oxidation of reduced FTMA to oxidized FTMA led to the desorption of surfactant molecules adsorbed at the interface of the octane/aqueous surfactant solution, leading to demulsification. PMID- 27402349 TI - Using Best-Worst Scaling to Investigate Preferences in Health Care. AB - INTRODUCTION: Best-worst scaling (BWS) is becoming increasingly popular to elicit preferences in health care. However, little is known about current practice and trends in the use of BWS in health care. This study aimed to identify, review and critically appraise BWS in health care, and to identify trends over time in key aspects of BWS. METHODS: A systematic review was conducted, using Medline (via Pubmed) and EMBASE to identify all English-language BWS studies published up until April 2016. Using a predefined extraction form, two reviewers independently selected articles and critically appraised the study quality, using the Purpose, Respondents, Explanation, Findings, Significance (PREFS) checklist. Trends over time periods (<=2010, 2011, 2012, 2013, 2014 and 2015) were assessed further. RESULTS: A total of 62 BWS studies were identified, of which 26 were BWS object case studies, 29 were BWS profile case studies and seven were BWS multi-profile case studies. About two thirds of the studies were performed in the last 2 years. Decreasing sample sizes and decreasing numbers of factors in BWS object case studies, as well as use of less complicated analytical methods, were observed in recent studies. The quality of the BWS studies was generally acceptable according to the PREFS checklist, except that most studies did not indicate whether the responders were similar to the non-responders. CONCLUSION: Use of BWS object case and BWS profile case has drastically increased in health care, especially in the last 2 years. In contrast with previous discrete-choice experiment reviews, there is increasing use of less sophisticated analytical methods. PMID- 27402352 TI - What Works to Reduce Unnecessary Care for Bronchiolitis? A Qualitative Analysis of a National Collaborative. AB - OBJECTIVE: Unnecessary care is well established as a quality problem affecting acute viral bronchiolitis, one of the most common pediatric illnesses. Although there is an extensive quality improvement literature on the disease, published work primarily reflects the experience of freestanding children's hospitals. We sought to better understand the specific barriers and drivers for successful quality improvement in community and nonfreestanding children's facilities. METHODS: We undertook a mixed methods study to identify correlates of success in a bronchiolitis quality improvement collaborative of community hospitals and children's hospitals within adult hospitals. We assessed site demographic characteristics, compliance with project interventions, and team engagement for association with end of project performance. We then used performance quartiles on a composite assessment of project measures (use of bronchodilators and steroids) to design a purposive sample of sites approached for qualitative interviews. RESULTS: Team engagement was the only factor quantitatively associated with better performance in the overall cohort. Fifteen sites, from the total cohort of 21, completed qualitative interviews. Qualitative themes around team engagement, including the presence of buy-in for successful sites and the inability to engage colleagues at unsuccessful sites, were important differentiating factors between top and bottom performance quartiles. Regardless of performance quartile, most programs cited intrainstitutional competition for limited resources to do quality improvement work as a specific barrier for pediatrics. The ability to overcome such barriers and specifically garner information technology (IT) resources also differentiated the top and bottom performance quartiles. CONCLUSIONS: Team engagement showed a consistent association with success across our quantitative and qualitative evaluations. Competition for limited resources in this cohort of nonfreestanding children's programs, particularly those in hospital IT, was a key qualitative theme. PMID- 27402351 TI - Using Address Information to Identify Hardships Reported by Families of Children Hospitalized With Asthma. AB - OBJECTIVE: Socioeconomic hardship is common among children hospitalized for asthma but often not practically measurable. Information on where a child resides is universally available. We sought to determine the correlation between neighborhood-level socioeconomic data and family-reported hardships. METHODS: Caregivers of 774 children hospitalized with asthma answered questions regarding income, financial strain, and primary care access. Addresses were geocoded and linked to zip code-, census tract-, and block group-level (neighborhood) data from the US Census. We then compared neighborhood median household income with family-reported household income; percentage of neighborhood residents living in poverty with family-reported financial strain; and percentage of neighborhood households without an available vehicle with family-reported access to primary care. We constructed heat maps and quantified correlations using Kendall rank correlation coefficient. Receiver operator characteristic curves were used to assess predictive abilities of neighborhood measures. RESULTS: The cohort was 57% African American and 73% publicly-insured; 63% reported income <$30,000, 32% endorsed >=4 financial strain measures, and 38% reported less than adequate primary care access. Neighborhood median household income was significantly and moderately correlated with and predictive of reported household income; neighborhood poverty was similarly related to financial strain; neighborhood vehicle availability was weakly correlated with and predictive of primary care access. Correlations and predictions provided by zip code measures were similar to those of census tract and block group. CONCLUSIONS: Universally available neighborhood information might help efficiently identify children and families with socioeconomic hardships. Systematic screening with area-level socioeconomic measures has the potential to inform resource allocation more efficiently. PMID- 27402353 TI - Injuries Associated With Strollers and Carriers Among Children in the United States, 1990 to 2010. AB - OBJECTIVE: To describe the incidence, rate, and characteristics of injuries associated with strollers and carriers among young children in the United States. METHODS: A retrospective analysis was conducted using data from the National Electronic Injury Surveillance System for children 5 years of age and younger treated in emergency departments (1990-2010), who sustained an injury associated with a stroller or carrier. RESULTS: An estimated 360,937 (95% confidence interval: 294,279-427,594) children aged 5 years or younger were treated in emergency departments for stroller- or carrier-related injuries, an average of 17,187 annually. Overall, the rate of stroller- and carrier-related injuries decreased significantly during the study period. Regarding stroller-related injuries, patients were most commonly male (52.4%) and younger than 1 year of age (42.0%); the head (43.0%) and face (31.0%) were most commonly injured. The most common diagnoses were soft tissue injuries (39.4%) and traumatic brain injuries/concussions (24.6%). Similarly, for carrier-related injuries, patients were most commonly male (52.5%) and younger than 1 year of age (89.0%); the head (61.5%) and face (24.7%) were most commonly injured. The most common diagnoses were soft tissue injuries (48.1%) and traumatic brain injuries/concussions (34.9%). Carrier-related injuries resulted in more hospitalizations (6.5%) than stroller-related injuries (2.4%). CONCLUSIONS: Stroller- and carrier-related injuries, specifically those resulting from falls from the product or tip-overs, are important sources of injury for children 5 years of age and younger. Although injuries over the 21-year study period decreased overall, the considerable number of injuries annually shows the need to further reduce the potential for injury associated with these ubiquitous products. PMID- 27402354 TI - Essential protein discovery based on a combination of modularity and conservatism. AB - Essential proteins are indispensable for the survival of a living organism and play important roles in the emerging field of synthetic biology. Many computational methods have been proposed to identify essential proteins by using the topological features of interactome networks. However, most of these methods ignored intrinsic biological meaning of proteins. Researches show that essentiality is tied not only to the protein or gene itself, but also to the molecular modules to which that protein belongs. The results of this study reveal the modularity of essential proteins. On the other hand, essential proteins are more evolutionarily conserved than nonessential proteins and frequently bind each other. That is to say, conservatism is another important feature of essential proteins. Multiple networks are constructed by integrating protein-protein interaction (PPI) networks, time course gene expression data and protein domain information. Based on these networks, a new essential protein identification method is proposed based on a combination of modularity and conservatism of proteins. Experimental results show that the proposed method outperforms other essential protein identification methods in terms of a number essential protein out of top ranked candidates. PMID- 27402355 TI - Modular magnetic tweezers for single-molecule characterizations of helicases. AB - Magnetic tweezers provide a versatile toolkit supporting the mechanistic investigation of helicases. In the present article, we show that custom magnetic tweezers setups are straightforward to construct and can easily be extended to provide adaptable platforms, capable of addressing a multitude of enquiries regarding the functions of these fascinating molecular machines. We first address the fundamental components of a basic magnetic tweezers scheme and review some previous results to demonstrate the versatility of this instrument. We then elaborate on several extensions to the basic magnetic tweezers scheme, and demonstrate their applications with data from ongoing research. As our methodological overview illustrates, magnetic tweezers are an extremely useful tool for the characterization of helicases and a custom built instrument can be specifically tailored to suit the experimenter's needs. PMID- 27402356 TI - Shock-refractory ventricular fibrillation in a patient implanted with a left ventricular assist device. PMID- 27402357 TI - A Comparative Analysis of 5-Azacytidine- and Zebularine-Induced DNA Demethylation. AB - The nonmethylable cytosine analogs, 5-azacytidine and zebularine, are widely used to inhibit DNA methyltransferase activity and reduce genomic DNA methylation. In this study, whole-genome bisulfite sequencing is used to construct maps of DNA methylation with single base pair resolution in Arabidopsis thaliana seedlings treated with each demethylating agent. We find that both inhibitor treatments result in nearly indistinguishable patterns of genome-wide DNA methylation and that 5-azacytidine had a slightly greater demethylating effect at higher concentrations across the genome. Transcriptome analyses revealed a substantial number of upregulated genes, with an overrepresentation of transposable element genes, in particular CACTA-like elements. This demonstrates that chemical demethylating agents have a disproportionately large effect on loci that are otherwise silenced by DNA methylation. PMID- 27402358 TI - A Split-Ubiquitin Based Strategy Selecting for Protein Complex-Interfering Mutations. AB - Understanding the topologies and functions of protein interaction networks requires the selective removal of single interactions. We introduce a selection strategy that enriches among a random library of alleles for mutations that impair the binding to a given partner protein. The selection makes use of a split ubiquitin based protein interaction assay. This assay provides yeast cells that carry protein complex disturbing mutations with the advantage of being able to survive on uracil-lacking media. Applied to the exemplary interaction between the PB domains of the yeast proteins Bem1 and Cdc24, we performed two independent selections. The selections were either analyzed by Sanger sequencing of isolated clones or by next generation sequencing (NGS) of pools of clones. Both screens enriched for the same mutation in position 833 of Cdc24. Biochemical analysis confirmed that this mutation disturbs the interaction with Bem1 but not the fold of the protein. The larger dataset obtained by NGS achieved a more complete representation of the bipartite interaction interface of Cdc24. PMID- 27402360 TI - ChloroSeq, an Optimized Chloroplast RNA-Seq Bioinformatic Pipeline, Reveals Remodeling of the Organellar Transcriptome Under Heat Stress. AB - Although RNA-Seq has revolutionized transcript analysis, organellar transcriptomes are rarely assessed even when present in published datasets. Here, we describe the development and application of a rapid and convenient method, ChloroSeq, to delineate qualitative and quantitative features of chloroplast RNA metabolism from strand-specific RNA-Seq datasets, including processing, editing, splicing, and relative transcript abundance. The use of a single experiment to analyze systematically chloroplast transcript maturation and abundance is of particular interest due to frequent pleiotropic effects observed in mutants that affect chloroplast gene expression and/or photosynthesis. To illustrate its utility, ChloroSeq was applied to published RNA-Seq datasets derived from Arabidopsis thaliana grown under control and abiotic stress conditions, where the organellar transcriptome had not been examined. The most appreciable effects were found for heat stress, which induces a global reduction in splicing and editing efficiency, and leads to increased abundance of chloroplast transcripts, including genic, intergenic, and antisense transcripts. Moreover, by concomitantly analyzing nuclear transcripts that encode chloroplast gene expression regulators from the same libraries, we demonstrate the possibility of achieving a holistic understanding of the nucleus-organelle system. ChloroSeq thus represents a unique method for streamlining RNA-Seq data interpretation of the chloroplast transcriptome and its regulators. PMID- 27402359 TI - Microsporidia Intracellular Development Relies on Myc Interaction Network Transcription Factors in the Host. AB - Microsporidia are ubiquitous parasites that infect a wide range of animal hosts, and these fungal-related microbes undergo their entire replicative lifecycle inside of host cells. Despite being widespread in the environment and causing medical and agricultural harm, virtually nothing is known about the host factors important to facilitate their growth and development inside of host cells. Here, we perform a genetic screen to identify host transcription factors important for development of the microsporidian pathogen Nematocida parisii inside intestinal cells of its natural host, the nematode Caenorhabditis elegans Through this screen, we identified the C. elegans Myc family of transcription factors as key host regulators of microsporidia growth and development. The Mad-like transcription factor MDL-1, and the Max-like transcription factors MXL-1 and MXL 2 promote pathogen levels, while the Myc-Mondo-like transcription factor MML-1 inhibits pathogen levels. We used epistasis analysis to show that MDL-1 and MXL 1, which are thought to function as a heterodimer, appear to be acting canonically. In contrast, MXL-2 and MML-1, which are also thought to function as a heterodimer, appear to be acting in separate pathways (noncanonically) in the context of pathogen infection. We also found that both MDL-1::GFP and MML-1::GFP are expressed in intestinal cells during infection. These findings provide novel insight into the host transcription factors that regulate microsporidia development. PMID- 27402361 TI - Sources of Error in Mammalian Genetic Screens. AB - Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID- 27402362 TI - Canopy Temperature and Vegetation Indices from High-Throughput Phenotyping Improve Accuracy of Pedigree and Genomic Selection for Grain Yield in Wheat. AB - Genomic selection can be applied prior to phenotyping, enabling shorter breeding cycles and greater rates of genetic gain relative to phenotypic selection. Traits measured using high-throughput phenotyping based on proximal or remote sensing could be useful for improving pedigree and genomic prediction model accuracies for traits not yet possible to phenotype directly. We tested if using aerial measurements of canopy temperature, and green and red normalized difference vegetation index as secondary traits in pedigree and genomic best linear unbiased prediction models could increase accuracy for grain yield in wheat, Triticum aestivum L., using 557 lines in five environments. Secondary traits on training and test sets, and grain yield on the training set were modeled as multivariate, and compared to univariate models with grain yield on the training set only. Cross validation accuracies were estimated within and across-environment, with and without replication, and with and without correcting for days to heading. We observed that, within environment, with unreplicated secondary trait data, and without correcting for days to heading, secondary traits increased accuracies for grain yield by 56% in pedigree, and 70% in genomic prediction models, on average. Secondary traits increased accuracy slightly more when replicated, and considerably less when models corrected for days to heading. In across environment prediction, trends were similar but less consistent. These results show that secondary traits measured in high-throughput could be used in pedigree and genomic prediction to improve accuracy. This approach could improve selection in wheat during early stages if validated in early-generation breeding plots. PMID- 27402363 TI - Covariance Between Genotypic Effects and its Use for Genomic Inference in Half Sib Families. AB - In livestock, current statistical approaches utilize extensive molecular data, e.g., single nucleotide polymorphisms (SNPs), to improve the genetic evaluation of individuals. The number of model parameters increases with the number of SNPs, so the multicollinearity between covariates can affect the results obtained using whole genome regression methods. In this study, dependencies between SNPs due to linkage and linkage disequilibrium among the chromosome segments were explicitly considered in methods used to estimate the effects of SNPs. The population structure affects the extent of such dependencies, so the covariance among SNP genotypes was derived for half-sib families, which are typical in livestock populations. Conditional on the SNP haplotypes of the common parent (sire), the theoretical covariance was determined using the haplotype frequencies of the population from which the individual parent (dam) was derived. The resulting covariance matrix was included in a statistical model for a trait of interest, and this covariance matrix was then used to specify prior assumptions for SNP effects in a Bayesian framework. The approach was applied to one family in simulated scenarios (few and many quantitative trait loci) and using semireal data obtained from dairy cattle to identify genome segments that affect performance traits, as well as to investigate the impact on predictive ability. Compared with a method that does not explicitly consider any of the relationship among predictor variables, the accuracy of genetic value prediction was improved by 10-22%. The results show that the inclusion of dependence is particularly important for genomic inference based on small sample sizes. PMID- 27402364 TI - Genomic Signatures of North American Soybean Improvement Inform Diversity Enrichment Strategies and Clarify the Impact of Hybridization. AB - Crop improvement represents a long-running experiment in artificial selection on a complex trait, namely yield. How such selection relates to natural populations is unclear, but the analysis of domesticated populations could offer insights into the relative role of selection, drift, and recombination in all species facing major shifts in selective regimes. Because of the extreme autogamy exhibited by soybean (Glycine max), many "immortalized" genotypes of elite varieties spanning the last century have been preserved and characterized using ~50,000 single nucleotide polymorphic (SNP) markers. Also due to autogamy, the history of North American soybean breeding can be roughly divided into pre- and posthybridization eras, allowing for direct interrogation of the role of recombination in improvement and selection. Here, we report on genome-wide characterization of the structure and history of North American soybean populations and the signature of selection in these populations. Supporting previous work, we find that maturity defines population structure. Though the diversity of North American ancestors is comparable to available landraces, prehybridization line selections resulted in a clonal structure that dominated early breeding and explains many of the reductions in diversity found in the initial generations of soybean hybridization. The rate of allele frequency change does not deviate sharply from neutral expectation, yet some regions bare hallmarks of strong selection, suggesting a highly variable range of selection strengths biased toward weak effects. We also discuss the importance of haplotypes as units of analysis when complex traits fall under novel selection regimes. PMID- 27402366 TI - Managing Syncope in the Elderly: The Not So Simple Faint in Aging Patients. AB - Providing care to the elderly patient with syncope poses problems that are unusual in their complexity. The differential diagnosis is broad, and sorting through it is made more difficult by the relative lack of symptoms surrounding the faint. Indeed, distinguishing faints from falls is often problematic. Many elderly patients are frail and are at risk of trauma if they should have an unprotected faint or fall to the ground. However, not all elderly patients are frail, and definitions of frailty vary. Providing accurate, effective, and appropriate care for the frail elderly patient who faints may require a multidisciplinary approach. PMID- 27402367 TI - Conceptual Models of Frailty: Accumulation of Deficits. AB - Frailty was introduced to explain why people of the same age have varying degrees of risk. The deficit accumulation approach shows that as people age, they accumulate health deficits, and that more deficits confer greater risk. Frailty results because not everyone of the same age has the same number of deficits. This is readily quantified using a frailty index, which has been translated to preclinical models. The frailty index grades risk without requiring special instrumentation. It allows a central clinical challenge to be addressed, which is that with age, diseases rarely travel alone. PMID- 27402365 TI - The Role of Stem Cell DNA Methylation in Colorectal Carcinogenesis. AB - Stems cells of the colon crypt are the origin of colon mature cells. Colorectal cancer cells are also suggested to originate from crypt stem cells undergoing a series of epigenetic and genetic alterations. Aberrant methylation plays important roles in early carcinogenesis and lead to altered gene expression and regulation, resulting in accumulation of damages to cell function and ultimately, malignant transformation. Aberrances in hypermethylation and hypomethylation act in different mechanism through the regulation of various genes during CSC carcinogenesis, and both of them play crucial roles in stem cell differentiation towards cancer cells. A large majority of epigenetic and genetic abnormalities that work coordinately in colorectal carcinogenesis are related to cell growth and division, indicating that the intrinsic abnormalities of CRC lie in dysregulation of basic cellular processes. Detection of abnormal methylation can be used in cancer screening and early detection, while reversal of aberrant methylation using drugs may have potential in cancer therapy. This review will provide an overview on the roles of aberrant methylation and a summary of genes that are affected during CRC carcinogenesis. PMID- 27402368 TI - Paul R. Manske 2015 Award for the Best Upper Extremity Congenital Research Manuscript. PMID- 27402369 TI - Letter regarding "Distal Limb Defects and Aplasia Cutis: Adams-Oliver Syndrome". PMID- 27402370 TI - The effect of alfuzosin on renal resistive index, urinary electrolytes and beta2 microglobulin levels and TGF beta-1 levels of kidney tissue in rats with unilateral ureteropelvic junction obstruction. AB - BACKGROUND: In this study, it was aimed to determine the effects of alfuzosin on experimentally generated unilateral partial ureteropelvic junction obstruction (UPO) in rats. MATERIALS AND METHODS: Thirty Long-Evans rats were randomly allocated into five groups. In control group (C), nothing was performed; in group Sham (S) only laparotomy was done; in Alfuzosin group (A) only alfuzosin was administered for two weeks (10 mg/kg/day p.o.) without any surgery; in UPO group, unilateral UP junction obstruction was produced; and in the Group UPT (ureteropelvic obstruction + treatment), alfuzosin was administered for two weeks (10 mg/kg/day p.o.) in addition to UPO production. Renal pelvic anteroposterior diameters were determined with ultrasonography (USG) and renal arterial resistivity indexes by color Doppler USG. Urine was collected both at the beginning and at the end of the experiment for 24 h in all the groups and at the end of the experiment, blood samples were obtained. Blood and urine electrolytes and TGF-beta1, urine density, urine beta2 microglobulin levels were determined. Renal tissue samples harvested from all of the rats were histopathologically evaluated. Results were determined using one-way ANOVA t-test; p < 0.05 was accepted as significant. RESULTS: Urine density in the UPT group was lower with respect to UPO group and blood electrolytes were preserved as close to normal (p < 0.05). In the UPT group, urine TGF-beta1 and blood TGF-beta1, blood beta2 microglobulin levels and histopathologic damage scores were lower compared to the UPO group (p < 0.05). CONCLUSION: It is shown in this experimental unilateral partial UPO model that alfuzosin treatment prevents obstructive renal damage. PMID- 27402372 TI - A Prospective Randomized Trial of the Effects of Early Enteral Feeding After Radical Cystectomy. AB - OBJECTIVE: To investigate the role of early feeding on recovery after radical cystectomy and urinary diversion. Enhanced recovery protocols have helped to standardize postoperative recovery. This is the first study to directly review the impact of early feeding on recovery in a randomized multi-institutional protocol. METHODS: From 2011 to 2014, patients at 2 large hospitals were randomized after radical cystectomy to receive access to liquids and then a regular diet on postoperative days 1 and 2 or conventional care with introduction of a liquid diet after return of bowel activity, typically days 3-5. Early ambulation, use of metoclopramide, and no nasogastric tube were standard for all patients. The study was powered to detect a 50% decrease in 90-day complication rate with secondary end points of length of stay, time to bowel activity, and time to diet tolerance. The study was terminated early due to slow accrual (102 of 328). RESULTS: Overall complications for the early vs standard groups were similar (34 vs 31, P = .86). Immediate inpatient and postdischarge complication rates were also similar (P = .63 and P = .44). Length of stay was not different (8.74 days vs 9.69 days, P = .43). Rates of ileus (27% vs 41%, P = .21) and return of bowel function (4.67 days vs 4.09 days, P = .62) were the same in arms. CONCLUSION: Although this prospective randomized study did not meet the accrual target, early introduction of diet was well tolerated and did not show a negative or positive difference in any outcomes. Enhanced recovery protocols standardize postoperative care and early feeding is a well-tolerated addition. PMID- 27402371 TI - Systemic therapy for bladder cancer finally comes into a new age. AB - Systemic therapy for bladder cancer, both localized muscle-invasive disease and metastatic disease, has seen minimal progress over the past two decades. Current approaches rely upon cytotoxic chemotherapy combinations aimed at increasing cure rates or achieving palliation and disease control, but these regimens are fraught with short- and long-term toxicities and outcomes remain suboptimal. The emergence of systemic immunotherapies that can provide durable remissions in subsets of patients with other malignancies has the potential to transform the field, and early phase trials have begun to demonstrate activity in some patients with metastatic bladder cancer. In this article, we review the current state of systemic therapy for bladder cancer and discuss the current literature and ongoing trials utilizing various immunotherapies. PMID- 27402373 TI - Racial Disparities Differ for African Americans and Hispanics in the Diagnosis and Treatment of Penile Cancer. AB - OBJECTIVE: To evaluate racial disparities in the diagnosis and treatment of penile cancer among a contemporary series of men from a large diverse national data base. MATERIALS AND METHODS: Using the 1998-2012 National Cancer Data Base, all men with squamous cell carcinoma (SCC) were stratified by race and ethnicity. Demographic and disease characteristics were compared between groups. Likelihood of undergoing surgery and type of surgery were compared among patients with nonmetastatic disease. Factors influencing disease stage and treatment type were analyzed with univariate and multivariable logistic regressions. Overall survival was examined with Kaplan-Meier and adjusted Cox proportional hazard models. RESULTS: We identified 12,090 men with penile SCC with median age 66 years (range 18-90). Distribution of patients is as follows: 76.8% Caucasian, 10.2% African American (AA), 8.7% Hispanic. On multivariable analysis, Hispanic men are more likely to present with high-risk (>=T1G3) penile SCC (odds ratio [OR] 1.6; confidence interval [CI] 1.20-2.00; P = .001) and tend to undergo penectomy rather than penile-sparing surgery (OR 1.46; CI 1.15-1.85; P = .002) for equal stage SCC compared to Caucasian patients. Whereas AA men are less likely to undergo surgery of any type (OR 0.67; CI 0.51-0.87; P = .003) and have higher mortality rates than Caucasian patients (hazard ratio 1.25; CI 1.10-1.42; P < .001). CONCLUSION: Hispanic men with penile SCC are more likely to present with high-risk disease and undergo more aggressive treatment than Caucasian patients but have comparable survival. AA men are less likely to undergo surgical management of their disease and have higher mortality rates. PMID- 27402375 TI - Potent and Selective Monoamine Oxidase-B Inhibitory Activity: Fluoro- vs. Trifluoromethyl-4-hydroxylated Chalcone Derivatives. AB - For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO-B inhibitors with a competitive mode of inhibition. The most active compound, (2E)-1-(4 hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one, exhibited a Ki value of 0.33 +/- 0.01 MUm toward hMAO-B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H-bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO-B selectivity and potency. PMID- 27402376 TI - Nonadiabatic dynamics of floppy hydrogen bonded complexes: the case of the ionized ammonia dimer. AB - In the case of the ammonia dimer, we address the following questions: how ultrafast ionization dynamics is controlled by hydrogen bonding and whether we can control the products via selective ionization of a specific electron. We use quantum chemical calculations and ab initio non-adiabatic molecular dynamics simulations to model the femtosecond dynamics of the ammonia dimer upon ionization. The role of nuclear quantum effects and thermal fluctuations in predicting the structure of the dimer is emphasized; it is shown that the minimum energy and vibrationally averaged structures are rather different. The ground state structure subsequently controls the ionization dynamics. We describe reaction pathways, electronic population transfers and reaction yields with respect to ionization from different molecular orbitals. The simulations showed that the ionized ammonia dimer is highly unstable and its decay rate is primarily driven by the position of the electron hole. In the case of ground state ionization (i.e. the HOMO electron is ionized), the decay is likely to be preceded by a proton transfer (PT) channel yielding NH4(+) and NH2 fragments. The PT is less intense and slower compared with the ionized water dimer. After ionizing deeper lying electrons, mainly NH3(+) and NH3 fragments are formed. Overall, our results show that the ionization dynamics of the ammonia and water dimers differ due to the nature of the hydrogen bond in these systems. PMID- 27402374 TI - Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study. AB - OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription. PMID- 27402377 TI - Current trends in candidemia and species distribution among adults: Candida glabrata surpasses C. albicans in diabetic patients and abdominal sources. AB - Candidemia rate and species distribution vary according to the type of patients, country of origin and antifungal prophylaxis use. To present current candidemia epidemiological trends. A retrospective examination of candidemia in adults (>=18 years-old) hospitalised from 2007 to 2015. Cases were identified through the microbiology laboratory. Candida species were distinguished based on colony morphology and VITEK-2 YBC cards, (bioMerieux, Durham, NC, USA). Patient characteristics, species distribution, source and outcome were assessed. We encountered 275 patients (294 episodes) with candidemia. The rate of candidemia dropped in 2010 (P = 0.003) without further decline. Nearly all cases (97.5%) were healthcare-associated. C. albicans (n = 118) and C. glabrata (n = 77) proportions varied without a discernable trend. C. glabrata was more common in diabetics [52.9% vs. 32.0% (non-diabetics); P = 0.004] and abdominal sources [53.3% vs. 35.5% (other sources); P = 0.03], especially gastric/duodenal foci [88.9% vs. 44.1% (other abdominal foci); P = 0.02]. All-cause 30-day mortality rate was 43.3% without changes over time or differences between C. albicans and C. glabrata. In conclusion, the candidemia rate remains stable after a decline in 2010. C. albicans remains the most common species but C. glabrata predominates in diabetics and abdominal sources. These findings suggest possible species-related differences in colonisation dynamics or pathogenicity. PMID- 27402378 TI - European guidelines for workplace drug and alcohol testing in hair. AB - Guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). They are based on the 2010 version published by Pascal Kintz and Ronald Agius (Guidelines for European workplace drug and alcohol testing in hair. Drug Test. Anal. 2010, 2, 367) and in concordance with the Society of Hair Testing guidelines (Society of Hair Testing guidelines for drug testing in hair. Forensic Sci. Int. 2012, 218, 20-24). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing use these guidelines as a template for accreditation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27402379 TI - Does Vidarabine Mediate Cardioprotection via Inhibition of AC5? AB - There is an ongoing discussion about the value of adenylyl cyclase 5 (AC5) as drug target for treatment of heart failure. This letter discusses statistical, pharmacokinetic, and pharmacodynamic reasons why the recently proposed cardioprotective effects of vidarabine cannot be readily attributed to AC5 inhibition. PMID- 27402380 TI - Response to Letter to the Editor on "Does Vidarabine Mediate Cardioprotection via Inhibition of AC5?". PMID- 27402382 TI - Super-spreading events of MERS-CoV infection. PMID- 27402381 TI - MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study. AB - BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. METHODS: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. FINDINGS: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0.0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2-17, IQR 5-10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4-8] vs 11 days [6-12]; p<0.0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. FUNDING: None. PMID- 27402383 TI - A descriptive analysis of the climbing mechanics of a mountain goat (Oreamnos americanus). AB - The mountain goat (Oreamnos americanus) is one of the most extraordinary mountaineers in the animal kingdom. While observational descriptions exist to indicate factors that may influence their climbing ability, these have never been assessed biomechanically. Here, we describe whole-body motion of a mountain goat during ascent of a 45 degrees incline based on a video recording in the Canadian Rocky Mountains, and discuss the results in a mechanical context. During the push off phase, the hindlimb extended and the forelimb was tucked close to the torso. During the pull-up phase, the hindlimb was raised near to the torso, while the forelimb humerus seemed to "lock" in a constant position relative to the torso, allowing the elbow to be held in close proximity to the whole-body center of mass. Extension of the elbow and carpal joints resulted in a vertical translation of the center of mass up the mountain slope. Based on the observations from this naturalistic study, hypotheses for future controlled studies of mountain goat climbing mechanics are proposed. PMID- 27402385 TI - Swyer-James-Macleod syndrome mimicking an acute pulmonary embolism: a report of six adult cases and a retrospective analysis. AB - BACKGROUND AND AIM: In patients with pulmonary embolism (PE), a pulmonary radiograph may reveal oligemic fields (the Westermark sign) associated with sites of occlusion of the pulmonary arteries, interruption or loss of the artery line (the knuckle sign), and even unilateral hyperlucency attributable to reduced overall lung vascularity. In Swyer-James-Macleod syndrome (SJMS), which develops as a result of bronchiolitis obliterans, unilateral hyperlucency is evident because of emphysema and hypoplasia of the pulmonary artery and its branches. Therefore, SJMS cases with clinical and laboratory data compatible with PE may in fact be confused with PE. The cases of six adult patients who were initially presumed to have PE but on further investigation were diagnosed with SJMS are presented in this report, which thus can serve as a guide for diagnosis of similar cases in future. METHODS: We studied six adult patients who presented with dyspnea. Their pulmonary radiographs revealed lobar/unilateral hyperlucency and PE was initially suspected. The pulmonary artery and branches thereof exhibited parenchymal emphysema and hypoplasia, and we thus diagnosed SJMS. RESULTS: We studied 4 males and 2 females with a mean age of 51 years (range, 20 73 years). Left lung involvement was evident in five cases. CONCLUSION: Unilateral hyperlucency may be a feature of both PE and SJMS. Although these conditions are very different, both present similarly in radiographic terms and may be easily confused when the clinical data and the anamnesis raise a suspicion of PE, causing unnecessary testing and treatment. PMID- 27402386 TI - [An unexpected cause of increased volume of the abdomen]. PMID- 27402384 TI - Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds. AB - Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (lambdamax) are evenly spaced across the light spectrum. In the course of avian evolution, the lambdamax of the most shortwave-sensitive cone, SWS1, has switched between violet (lambdamax > 400 nm) and ultraviolet (lambdamax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11',12'-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination. PMID- 27402387 TI - [Not Available]. PMID- 27402388 TI - [In memory of Prof. Dr. med. Wolfgang Hinkelbein : Honorary member of OGRO]. PMID- 27402389 TI - Novel technique for high-precision stereotactic irradiation of mouse brains. AB - BACKGROUND AND PURPOSE: Small animal irradiation systems were developed for preclinical evaluation of tumor therapy closely resembling the clinical situation. Mostly only clinical LINACs are available, so protocols for small animal partial body irradiation using a conventional clinical system are essential. This study defines a protocol for conformal brain tumor irradiations in mice. MATERIALS AND METHODS: CT and MRI images were used to demarcate the target volume and organs at risk. Three 6 MV photon beams were planned for a total dose of 10 fractions of 1.8 Gy. The mouse position in a dedicated applicator was verified by an X-ray patient positioning system before each irradiation. Dosimetric verifications (using ionization chambers and films) were performed. Irradiation-induced DNA damage was analyzed to verify the treatment effects on the cellular level. RESULTS: The defined treatment protocol and the applied fractionation scheme were feasible. The in-house developed applicator was suitable for individual positioning at submillimeter accuracy of anesthetized mice during irradiation, altogether performed in less than 10 min. All mice tolerated the treatment well. Measured dose values perfectly matched the nominal values from treatment planning. Cellular response was restricted to the target volume. CONCLUSION: Clinical LINAC-based irradiations of mice offer the potential to treat orthotopic tumors conformably. Especially with respect to lateral penumbra, dedicated small animal irradiation systems exceed the clinical LINAC solution. PMID- 27402390 TI - [Not Available]. PMID- 27402391 TI - Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes and Moderate Renal Impairment. AB - INTRODUCTION: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). The recommended dose of the dipeptidyl peptidase-4 inhibitor saxagliptin is 2.5 mg in patients with moderate or severe renal impairment (creatinine clearance <=50 mL/min). In this post hoc analysis, we assessed the effect of saxagliptin 2.5 and 5 mg/day versus placebo on glycemic measures in patients with T2D and estimated glomerular filtration rate 45-60 mL/min/1.73 m(2). METHODS: Efficacy and safety data were pooled from nine 24-week, randomized, placebo-controlled clinical trials. RESULTS: The majority (56-61%) of patients were women aged <65 years with glycated hemoglobin (A1C) 8.1-8.2%; half of the patients had a T2D duration >=5 years. Mean change from baseline in A1C was significantly greater with saxagliptin 2.5 (-0.6%, P = 0.036 vs placebo) and 5 mg/day (-0.9%, P < 0.001 vs placebo) compared with placebo (-0.2%). There were numerically greater reductions in fasting plasma glucose and 2-h postprandial glucose, and a significantly greater proportion of patients achieved A1C <7% with saxagliptin 5 mg/day (44.8%) compared with placebo (20.0%, P = 0.004 vs placebo). The incidence of hypoglycemia was not significantly different across groups (16.2% in the saxagliptin 5-mg/day, 12.2% in the saxagliptin 2.5-mg/day, and 11.3% in the placebo groups). CONCLUSION: These results suggest that saxagliptin 2.5 and 5 mg/day improve glycemic control and are generally well tolerated in patients with T2D and moderate CKD. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00121641, NCT00316082, NCT00698932, NCT00918879, NCT00121667, NCT00661362, NCT00313313, NCT00295633, NCT00757588. FUNDING: AstraZeneca, Gaithersburg, MD, USA. PMID- 27402392 TI - Cost-Effectiveness Analysis of d-Nav for People with Diabetes at High Risk of Neuropathic Foot Ulcers. AB - INTRODUCTION: The objective of this study was to assess the cost-effectiveness of the d-Nav Insulin Guidance Service (Hygieia Inc.), a system designed to improve glycemic control via the use of insulin titration, in people with diabetes at risk of developing neuropathic foot ulcers. METHODS: A Markov model containing four health states (no ulcer, uninfected ulcer, infected ulcer, and amputation) was developed to compare d-Nav with current National Health Service standard care. Patient movement between the health states was governed by event rates taken from the wider literature. Both the healing rate for uninfected ulcers and the rate of recurrence for uninfected ulcers were directly influenced by the patient's glycated hemoglobin (HbA1c). Separate mean HbA1c values were assigned to treatment and control patients and taken from a single-arm study that examined the effect of d-Nav on the outcomes of 122 patients, with HbA1c for control patients based on values recorded in the 12-month period prior to the study and HbA1c for d-Nav based on values recorded during the trial. Weekly cycles were applied, and patient resource use and quality-adjusted life years (QALYs) were estimated over a 3-year time horizon. Univariate sensitivity analysis was undertaken. RESULTS: In the base case, d-Nav was cost-saving and produced more QALYs than standard care, with a total net monetary benefit value of L1459 per patient. Univariate analysis indicated that the model results are relatively robust to variations in underlying parameters, with patient HbA1c having the most significant impact on outcomes. CONCLUSION: Interventions that aim to improve glycemic control, such as d-Nav, appear to be a cost-effective use of healthcare resources when targeted at those with poor glycemic control at high risk of developing foot ulcers. FUNDING: Hygieia Inc. PMID- 27402393 TI - Primary osteomyelitis caused by hypervirulent Klebsiella pneumoniae. AB - Klebsiella pneumoniae is the most clinically relevant species of this genus, known to cause both community-acquired and nosocomial infections worldwide. In the past two decades, a distinct hypervirulent strain of K pneumoniae, characterised by its hypermucoviscous phenotype, has emerged as a clinically significant pathogen responsible for highly invasive infections. We present a case of osteomyelitis due to hypervirulent K pneumoniae reported in the USA. Genomic testing of the K pneumoniae isolate was performed due to the striking clinical presentation of the infection as well as the hypermucoid nature of the isolates, raising the suspicion for possible infection with the hypervirulent strain. Whole-genome sequencing and additional PCR testing demonstrated the isolate to be a K1 serotype, sequence type 23 strain expressing rmpA and rmpA2. Given the multiple reports of this pathogen causing invasive infections, clinicians should be aware of the possible presentation of metastatic and severe infection, including osteomyelitis, due to the hypervirulent strain of K pneumoniae not typical of classic K pneumoniae variants. In this Grand Round, we review the clinical features of hypervirulent K pneumoniae and its link to invasive infections, and discuss the need for improved awareness and identification of the pathogen. PMID- 27402394 TI - The Association of Age With Short-Term and Long-Term Mortality in Adults Admitted to the Intensive Care Unit. AB - BACKGROUND: Based on the current literature, it is unclear whether advanced age itself leads to higher mortality in critically ill patients or whether it is due to the greater number of comorbidities in the elderly patients. We hypothesized that increasing age would increase the odds of short-term and long-term mortality after adjusting for baseline comorbidities in intensive care unit (ICU) patients. METHODS: We performed a retrospective cohort study of 57 160 adults admitted to any ICU over 5 years at 2 academic tertiary care centers. Patients were divided into age-groups, 18 to 39, 40 to 59, 60 to 79, and >=80. The primary outcomes were 30-day and 365-day mortality. Results were analyzed with multivariate logistic regression adjusting for demographics and the Elixhauser-van Walraven Comorbidity Index. RESULTS: The adjusted 30-day mortality odds ratios (ORs) were 1.39 (95% confidence interval [CI]: 1.21-1.60), 2.00 (95% CI: 1.75-2.28), and 3.33 (95% CI: 2.90-3.82) for age-groups 40 to 59, 60 to 79, and >=80, respectively, using the age-group 18 to 39 as the reference. The adjusted 365-day mortality ORs were 1.46 (95% CI: 1.32-1.61), 2.10 (95% CI: 1.91-2.31), and 2.96 (95% CI: 2.67-3.27). CONCLUSION: In critically ill patients, increasing age is associated with higher odds of short-term and long-term death after correcting for existing comorbidities. PMID- 27402395 TI - Association of Arterial Oxygen Tension During In-Hospital Cardiac Arrest With Return of Spontaneous Circulation and Survival. AB - BACKGROUND: Despite numerous advances in the delivery of resuscitative care, in hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. We sought to study the impact of arterial oxygen tension (Pao2) on return of spontaneous circulation (ROSC) and survival to discharge in patients with IHCA. METHODS: The study population included 255 consecutive patients who underwent advanced cardiac life support-guided resuscitation from January 2012 to December 2013 for IHCA at an academic tertiary medical center. Of these patients, 167 underwent arterial blood gas testing at the time of the arrest. Baseline demographic, clinical, laboratory, and clinical outcome data were recorded. The primary outcome of interest was survival to hospital discharge. Secondary outcome of interest was presence of ROSC. RESULTS: Of the 167 patients studied, Pao2 categorization included the following: Pao2 < 60 mm Hg (n = 38), Pao2 of 60-92 mm Hg (n = 44), Pao2 of 93 to 159 mm Hg (n = 43), Pao2 of 160 to 299 mm Hg (n = 24), and Pao2 >= 300 mm Hg (n = 18). Patients with higher Pao2 levels during the time of cardiac arrest were noted to have higher rates of hypertension and chronic kidney disease. Clinical presentation of IHCA, in particular, the initial rhythm, location of IHCA, and duration of cardiopulmonary resuscitation, was similar in all groups. Patients with higher Pao2 levels had higher platelet count, higher arterial pH, and lower arterial carbon dioxide tension (Pco2). With respect to outcomes, patients with higher intra-arrest Pao2 levels had progressively higher rates of ROSC (58% vs 71% vs 72% vs 79% vs 100%, P = .021) and survival to discharge (16% vs 23% vs 30% vs 33% vs 56%, P = .031). In multivariate analysis, Pao2 >= 300 mm Hg was independently associated with higher survival to discharge (odds ratio 60.68; 95% confidence interval: 3.04-1210.28; P = .007; referent Pao2 < 60 mm Hg). CONCLUSION: Higher intra-arrest Pao2 is independently associated with higher rates of survival to discharge in adults with IHCA. PMID- 27402396 TI - Diagnostic Bedside Ultrasonography for Acute Respiratory Failure and Severe Hypoxemia in the Medical Intensive Care Unit: Basics and Comprehensive Approaches. AB - Bedside goal-directed ultrasound is a powerful tool for rapid differential diagnosis and monitoring of cardiopulmonary disease in the critically ill patient population. The bedside intensivist is in a unique position to integrate ultrasound findings with the overall clinical situation. Medically critically ill patients who require urgent bedside diagnostic assessment fall into 2 categories: (1) acute respiratory failure and (2) hemodynamic derangements. The first portion of this review outlines the diagnostic role of bedside ultrasound in the medically critically ill patient population for the diagnosis and treatment of acute respiratory failure, acute respiratory distress, and severe hypoxemia. The second portion will focus on the diagnostic role of ultrasound for the evaluation and treatment of shock states, as well as describe protocolized approaches for evaluation of shock during cardiopulmonary resuscitation. Different respiratory system pathologies that result in acute respiratory failure (such as increased interstitial fluid, alveolar consolidation, pleural effusion) cause characteristic ultrasonographic findings; diaphragmatic assessment may also add information. Intracardiac shunting can cause severe hypoxemia. Protocolized approaches for the evaluation of patients with acute respiratory failure or distress are discussed. PMID- 27402397 TI - Emotional discussions reduce memory recall. AB - People often discuss events they have seen and these discussions can influence later recollections. We investigated the effects of factual, emotional, and free retelling discussion on memory recollections of individuals who have witnessed an event. Participants were shown a video, made an initial individual recall, participated in one of the three retelling conditions (emotional versus factual versus free) or a control condition, and then recalled the event individually again. Participants in the factual and free retelling conditions reported more items not previously recalled than participants in the control condition did, while the emotional condition did not show the same advantage. Participants in all three retelling conditions failed to report more previously recalled items as compared with the control condition. Finally, a memory conformity effect was observed for all three retelling conditions. These findings suggest that eyewitnesses' discussions may influence the accuracy of subsequent memory reports, especially when these discussions are focused on emotional details and thoughts. PMID- 27402398 TI - A multicenter phase II trial of S-1 combined with bevacizumab after platinum based chemotherapy in patients with advanced non-squamous non-small cell lung cancer. AB - OBJECTIVES: This phase II trial investigated the efficacy and safety of S-1 plus bevacizumab (SB) after failure of platinum-based chemotherapy in patients with non-squamous non-small cell lung cancer (non-sq NSCLC). METHODS: Patients with non-sq NSCLC who had undergone prior platinum-based chemotherapy, regardless of the use of bevacizumab, were eligible. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, and bevacizumab (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS). RESULTS: Twenty-eight patients (14 males and 14 females; median age 62 years; performance status 0/1/2: 21/7/0) were accrued from 4 centers. Almost half (n = 15, 53.6 %) of these had received prior bevacizumab therapy. The median PFS and overall survival were 3.2 months [95 % confidence interval (CI) 2.2-4.0 months] and 11.4 months (95 % CI 8.9-13.9 months), respectively. Prior exposure to bevacizumab did not affect the PFS. An objective response was observed in 4 patients, the response rate and disease control rate being 14.3 and 85.7 %, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75 %) and fatigue (68 %). CONCLUSION: Although SB was well tolerated, this combination did not provide any additional benefit in terms of PFS for patients with non-sq NSCLC after failure of platinum-based chemotherapy. It will be important to clarify the most suitable agent for use with bevacizumab, and the optimal timing of bevacizumab therapy for lung cancer. PMID- 27402399 TI - Ablation and resection for hepatocellular carcinoma within Milan criteria and high alpha-foetoprotein levels. PMID- 27402400 TI - Scleral gas permeable lenses have come of age. PMID- 27402401 TI - Effects of sulfur-metabolizing bacterial community diversity on H2S emission behavior in landfills with different operation modes. AB - Hydrogen sulfide (H2S) is one of the major contributors to offensive odors from landfills, and its concentration differs under different operation modes. This study examined the distribution of H2S emission from different landfill depths under different operation modes (anaerobic, semi-aerobic, semi-aerobic transformation, and the three operation modes with additional leachate recirculation). The microbial community (especially the sulfur-metabolizing bacterial community) was investigated using high-throughput sequencing technology. The results showed that the semi-aerobic mode could substantially lower the risks of H2S pollution in landfills, which might be because of the difference in biological processes related to sulfur metabolism driven by functional microbes. A myriad of factors are responsible for mutually shaping the sulfur-metabolizing bacterial community composition in landfills that might subsequently affect the behavior of H2S emission in landfills. The differences in abundance of the genera Acinetobacter and Paracoccus (phylum Proteobacteria) caused by environmental factors might explain the differences in H2S emission. H2S odor control could be realized if the related functional microbe diversity can be influenced by adjustments to landfill operation. PMID- 27402402 TI - Mitochondrial complex I dysfunction and altered NAD(P)H kinetics in rat myocardium in cardiac right ventricular hypertrophy and failure. AB - AIMS: In cardiac hypertrophy (CH) and heart failure (HF), alterations occur in mitochondrial enzyme content and activities but the origin and implications of these changes for mitochondrial function need to be resolved. METHODS AND RESULTS: Right ventricular CH or HF was induced by monocrotaline injection, which causes pulmonary artery hypertension, in rats. Results were compared with saline injection (CON). NAD(P)H and FAD autofluorescence were recorded in thin intact cardiac trabeculae during transitions in stimulation frequency, to assess mitochondrial complex I and complex II function, respectively. Oxygen consumption, mitochondrial morphology, protein content, and enzymatic activity were assessed. NAD(P)H autofluorescence upon an increase in stimulation frequency showed a rapid decline followed by a slow recovery. FAD autofluorescence followed a similar time course, but in opposite direction. The amplitude of the early rapid change in NAD(P)H autofluorescence was severely depressed in CH and HF compared with CON. The rapid changes in FAD autofluorescence in CH and HF were reduced to a lesser extent. Complex I-coupled respiration showed an ~3.5-fold reduction in CH and HF; complex II-coupled respiration was depressed two-fold in HF. Western blot analyses revealed modest reductions in complex I protein content in CH and HF and in complex I activity in supercomplexes in HF. Mitochondrial volume density was similar, but mitochondrial remodelling was evident from changes in ultrastructure and fusion/fission indices in CH and HF. CONCLUSION: These results suggest that the alterations in mitochondrial function observed in right ventricular CH and HF can be mainly attributed to complex I dysfunction. PMID- 27402403 TI - Challenges of development and implementation of point of care pharmacogenetic testing. AB - INTRODUCTION: Just as technology was the underlying driver of the sequencing of the human genome and subsequent generation of volumes of genome sequence data from healthy and affected individuals, animal, plant, and microbial species alike, so too will technology revolutionize diagnostic testing. One area of intense interest is the use of genetic data to inform decisions regarding drug selection and drug dosing, known as pharmacogenetic (PGx) testing, to improve likelihood of successful treatment outcomes with minimal risks. AREAS COVERED: This commentary will provide an overview of implementation research of PGx testing, the benefits of point-of-care (POC) testing and overview of POC testing platforms, available PGx tests, and barriers and facilitators to the development and integration of POC-PGx testing into clinical settings. Sources include the published literature, and databases from the Centers for Medicaid and Medicare Services, Food and Drug Administration. Expert commentary: The utilization of POC PGx testing may enable more routine test use, but the development and implementation of such tests will face some barriers before personalized medicine is available to every patient. In particular, provider training, availability of clinical decision supports, and connectivity will be key areas to facilitate routine use. PMID- 27402404 TI - Relationship of dorsal root ganglion to intervertebral foramen in lumbar region: an anatomical study and review of literature. AB - BACKGROUND: The purpose of this study was to clarify the morphologic features, location and variations of the dorsal root ganglion (DRG). METHODS: Fifteen formalin fixed cadavers for the current study were included. Total of 150 DRGs were examined from L1 to L5. The relationships of the nerve root DRGs to the intervertebral foramen were noted. Position of the DRG was classified by the location of the ganglia in relation to the pedicle. The relationship of the DRG to the intervertebral foramen was evaluated. RESULTS: The distance between the midpoint of the DRG to the cross section of the root with the medial border of the pedicle gradually increased from L1 to L5. The medial border of the foramen distances along the nerve root were L1, 1.77 mm; L2, 2.79 mm; L3, 3.23 mm; L4, 7.28 mm and L5, 8.31 mm. The mean width of the lumbar DRGs were L1, 4.36 mm; L2, 4.56 mm; L3, 4.99 mm; L4, 5.22 mm and L5, 5.82 mm. The mean length of DRGs were as follows: L1, 5.39 mm; L2, 5.83 mm; L3, 7.24 mm; L4, 7.97 mm and L5, 10.83 mm. The mean width and length of DRGs gradually increased from L1 to L5. CONCLUSIONS: The DRG in the lumbar region play a key role in the occurence of low-back pain and sciatica; therefore, it is important to understand the anatomy of DRG. The accurate anatomic information about the position of DRGs would be useful to perform a safe surgical intervention in the lumbar foraminal region. PMID- 27402405 TI - The role of stenosis ratio as a predictor of surgical satisfaction in patients with lumbar spinal canal stenosis: a receiver-operator characteristic (ROC) curve analysis. AB - BACKGROUND: The aim of this study was to elucidate independent factors that predict surgical satisfaction in lumbar spinal canal stenosis (LSCS) patients. METHODS: Patients who underwent surgery were grouped based on the age, gender, duration of symptoms, walking distance, Neurogenic Claudication Outcome Score (NCOS) and the stenosis ratio (SR) described by Lurencin. We recorded on 2-year patient satisfaction using standardized measure. The optimal cut-off points in SR, NCOS and walking distance for predicting surgical satisfaction were estimated from sensitivity and specificity calculations and receiver operator characteristic (ROC) curves. RESULTS: One hundred fifty consecutive patients (51 male, 99 female, mean age 62.4+/-10.9 years) were followed up for 34+/-13 months (range 24-49). One, two, three and four level stenosis was observed in 10.7%, 39.3%, 36.0 % and 14.0% of patients, respectively. Post-surgical satisfaction was 78.5% at the 2 years follow up. In ROC curve analysis, the asymptotic significance is less than 0.05 in SR and the optimal cut-off value of SR to predict worsening surgical satisfaction was measured as more than 0.52, with 85.4% sensitivity and 77.4% specificity (AUC 0.798, 95% CI 0.73-0.90; P<0.01). CONCLUSIONS: The present study suggests that the SR, with a cut-off set a 0.52 cross-sectional area, may be superior to walking distance and NCOS in patients with degenerative lumbar stenosis considered for surgical treatment. Using a ROC curve analysis, a radiological feature, the SR, demonstrated superiority in predicting patient satisfaction, compared to functional and clinical characteristics such as walking distance and NCOS. PMID- 27402406 TI - Acute bilateral oculomotor paralysis and progressive visual loss after Valsalva maneuver during scuba diving. PMID- 27402407 TI - TGF-beta1 polymorphism in glioma. PMID- 27402408 TI - Acute postoperative sialadenitis after retrosigmoid craniotomies. PMID- 27402409 TI - Ataxic gait due to posterior thoracic spinal cord compression by a Tarlov cyst. PMID- 27402410 TI - Full endoscopic transforaminal endoscopic approach for symptomatic lumbar disc herniation, our experience. PMID- 27402411 TI - Rare case of brain metastasis of Ewing sarcoma mimicking cavernous angioma: new implications concerning management and therapy. PMID- 27402412 TI - Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms. AB - A wealth of research over the past 2 decades has expanded our understanding of the impact of early-life adversity on physiological function and, consequently, health and wellbeing in later life. Early-life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome. Although much of the research has examined the impact of physical maltreatment, an increasing number of studies have been published over the past few years examining the effect of childhood psychological stress and trauma on the development of various types of chronic pain conditions. We review the clinical and preclinical data examining the link among early-life psychological stress, altered nociceptive behavior, and chronic pain in later life. Evidence supporting a role for certain key neurobiological substrates, including the hypothalamic-pituitary-adrenal axis; monoaminergic, opioidergic, endocannabinoid and immune systems; and epigenetic mechanisms in the association between early-life psychological stress and chronic pain, is provided. Greater understanding of the impact of early-life stress may inform the development of personalized treatments for chronic pain in later life and strategies to prevent its onset in susceptible individuals. (c) 2016 Wiley Periodicals, Inc. PMID- 27402413 TI - Fabrication of a nano-drug delivery system based on layered rare-earth hydroxides integrating drug-loading and fluorescence properties. AB - We demonstrate the first example of intercalation of naproxen (abbr. NPX) into layered europium hydroxide (LEuH) and investigate the structure, chemical composition, thermostability, morphology, luminescence properties, cytotoxic effect, and controlled-release behaviors. Different deprotonation degrees lead to NPX-LEuH composites with diverse structures (horizontal or vertical arrangement), and the thermal stability of organics is enhanced after intercalation. The Eu(3+) luminescence in NPX-LEuH composites is enhanced, especially for the NPX-LEuH-1 : 0.5 composite. The content of naproxen in the intercalation material can be confirmed by HPLC. The cytotoxic effect of LEuH is observed with a sulforhodamine B (SRB) colorimetric assay, which reveals that the LEuH has low cytotoxic effects on most cells. In addition, the NPX-LEuH nanocomposites can control the release of NPX in Na2HPO4-NaH2PO4 buffer solution at pH 6.86 and 37 degrees C, and the complete release needs about 200 min. The release mechanism can be ascribed to the ion-exchange reaction between NPX and HPO4(2-)/H2PO4(-) in bulk solution. The ion-exchange velocity is fast at the beginning and slows down gradually with the exchange reaction. The construction of LRH composites with drug molecules provides a beneficial pathway for preparing a nano-drug delivery system based on LRHs integrating drug-loading and fluorescence properties. PMID- 27402415 TI - Fiber-reinforced interim fixed dental prostheses: A clinical protocol. AB - Repairing or refabricating interim fixed dental prostheses can be a source of frustration in terms of lost productivity and inconvenience to the patient. The technique for reinforcing interim fixed dental prosthetic restorations described here will provide added strength and durability. The technique can be used either indirectly or for the direct intraoral fabrication of the interim prosthesis, thereby yielding predictable and esthetic results. PMID- 27402414 TI - Dysregulation of Striatal Dopamine Receptor Binding in Suicide. AB - Inconsistent evidence implicates disruptions of striatal dopaminergic indices in suicide and major depression. To determine whether there are alterations in the striatal dopamine system in suicide, we conducted a quantitative autoradiographic survey of dopamine transporter (DAT; [3H]mazindol), D1 receptor ([3H]SCH23390), and D2 receptor ([3H]sulpiride) binding in the dorsal striatum postmortem from matched suicides and controls. Axis I and axis II psychiatric diagnosis, recent treatment history, and early life adversity (ELA) were determined by psychological autopsy. Mean DAT, D2, and D1 receptor binding did not differ in suicide. However, there was a positive correlation between D1 and D2 receptor binding in the dorsal striatum of control subjects (R2=0.31, p<0.05) that was not present in suicides (R2=0.00, p=0.97). In suicides and controls with reported ELA, there was no correlation between striatal DAT and D1 receptor binding (R2=0.07, p=0.33), although DAT and D1 receptor binding was positively correlated in subjects with no report of ELA (R2=0.32, p<0.05). After controlling for age, there were no significant ELA-related mean differences. Binding of D1 receptors and DAT throughout the striatum correlated negatively with age (D1 receptor: R2=0.12, p<0.05; DAT: R2=0.36, p<0.001). There appears to be an imbalance in dopaminergic receptor and transporter expression related to suicide that differs from that associated with ELA or age. PMID- 27402416 TI - Evaluation of patient experience and satisfaction with CAD-CAM-fabricated complete dentures: A retrospective survey study. AB - STATEMENT OF PROBLEM: Reports of sound, evidence-based treatment outcomes of computer-aided design and computer-aided manufacture (CAD-CAM) of complete dentures (CD) are lacking in publication databases. PURPOSE: The purpose of this retrospective survey study was to assess patient preferences and satisfaction when treated with digitally fabricated CDs, by using a questionnaire. MATERIAL AND METHODS: A total of 50 patients who received digital CDs were included in this study. A 10-item questionnaire was sent to the patients in order to assess their satisfaction with their digital CD experience. The items, or statements listed, were concerned with patient satisfaction and also the treatment technique and final outcome. Results of patient satisfaction questions were evaluated using descriptive statistics, means, and medians. All statistical tests were performed using commercially available software. Responses to the questionnaire provided by patients were analyzed using the Mantel-Haenszel chi-squared test (alpha=.05). RESULTS: The questionnaire was sent to 50 patients, and the total patient response rate after treatment intervention was 38% (n=19). Data obtained from questionnaire responses revealed that patients were generally pleased and satisfied with digital CDs. The chi-squared test results revealed no statistically significant differences (P=.180) in the ratings of experienced CD wearers. However, 70% of experienced CD patients agreed that their new digital CDs were "better" than their previous set of CDs. In all categories evaluated, patients gave positive responses regarding their digital CDs. CONCLUSIONS: Results of this questionnaire-driven study suggest that ratings from experienced CD wearers rehabilitated with CAD-CAM-fabricated CDs did not differ significantly from their previous ratings of conventional CDs, but overall, their satisfaction ratings of their digital CDs tended to be positive. PMID- 27402417 TI - An alternative impression technique for mobile teeth. AB - The impression technique described combines elastomeric impression materials and irreversible hydrocolloid to make an accurate preliminary impression of extremely mobile and misaligned teeth. Upon setting, the materials are removed from the mouth in 3 different directions and reassembled extraorally. This technique provides an alternative, easy, accurate, and safe way to make a preliminary impression of mobile, periodontally involved teeth. PMID- 27402418 TI - Influence of implant abutment material on the color of different ceramic crown systems. AB - STATEMENT OF PROBLEM: Ceramics are widely used for anterior restorations; however, clinical color reproduction still constitutes a challenge particularly when the ceramic crowns are used on titanium implant abutments. PURPOSE: The purpose of this in vitro study was to investigate the effect of implant abutment material on the color of different ceramic material systems. MATERIAL AND METHODS: Forty disks (11*1.5 mm, shade A2) were fabricated from medium-opacity (mo) and high-translucency (ht) lithium disilicate (IPS e.max) blocks, an aluminous ceramic (VITA In-Ceram Alumina), and a zirconia (Zirkonzahn) ceramic system. Disks were fabricated to represent 3 different implant abutments (zirconia, gold-palladium, and titanium) and dentin (composite resin, A2 shade) as background (11*2 mm). Disk-shaped composite resin specimens in A2 shade were fabricated to represent the cement layer. The color measurements of ceramic specimens were made on composite resin abutment materials using a spectrophotometer. CIELab color coordinates were recorded, and the color coordinates measured on composite resin background served as the control group. Color differences (DeltaE00) between the control and test groups were calculated. The data were analyzed with 2-way analysis of variance (ANOVA) and compared with the Tukey HSD test (alpha=.05). RESULTS: The ceramics system, abutment material, and their interaction were significant for DeltaE00 values (P<.001). Clinically unacceptable results (DeltaE00>2.25) were observed for lithium disilicate ceramics on titanium abutments (2.46-2.50). The DeltaE00 values of lithium disilicate ceramics for gold-palladium and titanium abutments were significantly higher than for other groups (P<.05). CONCLUSION: The color results (DeltaE00>2.25) of an implant-supported lithium disilicate ceramic restoration may be clinically unacceptable if it is fabricated over a titanium abutment. Zirconia may be a more suitable abutment material for implant-supported ceramic restorations. PMID- 27402419 TI - U.S. Demand for Tobacco Products in a System Framework. AB - This study estimated a system of demand for cigarettes, little cigars/cigarillos, large cigars, e-cigarettes, smokeless tobacco, and loose smoking tobacco using market-level scanner data for convenience stores. We found that the unconditional own-price elasticities for the six categories are -1.188, -1.428, -1.501, -2.054, -0.532, and -1.678, respectively. Several price substitute (e.g., cigarettes and e-cigarettes) and complement (e.g., cigarettes and smokeless tobacco) relationships were identified. Magazine and television advertising increased demand for e-cigarettes, and magazine advertising increased demand for smokeless tobacco and had spillover effects on demand for other tobacco products. We also reported the elasticities by U.S. census regions and market size. These results may have important policy implications, especially viewed in the context of the rise of electronic cigarettes and the potential for harm reduction if combustible tobacco users switch to non-combustible tobacco products. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27402420 TI - Patch test results with rubber series in the European Surveillance System on Contact Allergies (ESSCA), 2013/14. AB - BACKGROUND: Contact allergy to rubber additives is common, particularly in patients with occupational dermatitis. OBJECTIVES: To descriptively analyse and compare patch test reactions in patients patch tested both with the baseline series and with an additional 'rubber series' as used in the department. METHODS: Patch test data from those members of the European Surveillance System on Contact Allergies (ESSCA) network (www.essca-dc.org) who also contributed data on rubber series patch test results were retrospectively analysed. RESULTS: Among 29 522 patients patch tested, 2870 were eligible, that is, patch tested both with the baseline series and with a special rubber series. Of these, 8.8% had positive reaction(s) to one of the baseline screening rubber allergens (as compared with 4.2% in all patients), most often to carba mix, 12.3% had positive reaction(s) to allergens from an additional rubber series, and 6.4% had positive reaction(s) to both. CONCLUSIONS: Additional testing with a dedicated rubber series, containing break-down single ingredients of mixes from the baseline series and additional rubber allergens, is warranted in patients with suspected contact allergy to rubber, to avoid false-negative results. PMID- 27402421 TI - Dominant plasmids carrying extended-spectrum beta-lactamases blaCTX-M genes in genetically diverse Escherichia coli from slaughterhouse and urban wastewaters. AB - Wastewater treatment plants (WWTP) receiving effluents from food-producing animals and humans may contribute to the spread of extended-spectrum beta lactamases (ESBL)-carrying plasmids. This study was designed to investigate extended-spectrum cephalosporin resistant Escherichia coli strains, CTX-M distributions and the genetic lineage of blaCTX-M -carrying plasmids from urban and slaughterhouse wastewaters. The level of extended-spectrum cephalosporin resistant E. coli in slaughterhouse wastewater entering the WWTP was negligible compared with that of urban wastewater. The blaCTX-M-1 gene was predominant in slaughterhouse wastewater whereas diverse blaCTX-M genes were encountered in urban wastewater and WWTP outlet. Characterization of the main CTX-M-producing E. coli isolates by antibiotic resistance phenotyping, genotyping and typing of plasmids carrying blaCTX-M genes revealed that blaCTX-M-1 and blaCTX-M-15 genes were harboured by the predominant blaCTX-M-1 IncI1/ST3 and blaCTX-M-15 F31:A4:B1 plasmids, which were recovered from unrelated E. coli genotypes in both slaughterhouse and urban wastewaters. This study highlighted the spread of predominant blaCTX-M-1 and blaCTX-M-15 plasmid lineages in diverse E. coli genotypes from humans and food-producing animals, their mixing in WWTP and final release into the aquatic environment. This could have a serious negative impact on public health and requires further evaluation. PMID- 27402422 TI - 1 H and 13 C NMR spectral assignments of 1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1 phenylene))bis(methylene))-bispyridinium and -bisquinolinium bromide derivatives. PMID- 27402423 TI - [Is there a link between marijuana use and the risk of having psychiatric disorders?] PMID- 27402424 TI - Perioperative management of pediatric en-bloc combined heart-liver transplants: a case series review. AB - BACKGROUND: Combined heart and liver transplantation (CHLT) in the pediatric population involves a complex group of patients, many of whom have palliated congenital heart disease (CHD) involving single ventricle physiology. OBJECTIVE: The purpose of this study was to describe the perioperative management of pediatric patients undergoing CHLT at a single institution and to identify management strategies that may be used to optimize perioperative care. METHODS: We did a retrospective database review of all patients receiving CHLT at a children's hospital between 2006 and 2014. Information collected included preoperative characteristics, intraoperative management, blood transfusions, and postoperative morbidity and mortality. RESULTS: Five pediatric CHLTs were performed over an 8-year period. All patients had a history of complex CHD with multiple sternotomies, three of whom had failing Fontan physiology. Patient age ranged from 7 to 23 years and weight from 29.5 to 68.5 kg. All CHLTs were performed using an en-bloc technique where both the donor heart and liver were implanted together on cardiopulmonary bypass (CPB). The median operating room time was 14.25 h, median CPB time was 3.58 h, and median donor ischemia time was 4.13 h. Patients separated from CPB on dopamine, epinephrine, and milrinone infusions and two required inhaled nitric oxide. All patients received a massive intraoperative blood transfusion post CPB with amounts ranging from one to three times the patient's estimated blood volume. The patient who required the most transfusions was in decompensated heart and liver failure preoperatively. Four of the five patients received an antifibrinolytic agent as well as a procoagulant (prothrombin complex concentrate or recombinant activated Factor VII) to assist with hemostasis. There were no 30-day thromboembolic events detected. Postoperatively the median length of mechanical ventilation, ICU stay and stay to hospital discharge was 4, 8, and 37 days, respectively. All patients are alive and free from allograft rejection at this time. CONCLUSION: Combined heart and liver transplantation in the pediatric population involves a complex group of patients with unique perioperative challenges. Successful management starts with thorough preoperative planning and communication and involves strategies to deal with massive intraoperative hemorrhage and coagulopathy in addition to protecting and supporting the transplanted heart and liver and meticulous surgical technique. An integrated multidisciplinary team approach is the cornerstone for successful outcomes. PMID- 27402425 TI - De novo peptide sequencing using CID and HCD spectra pairs. AB - In tandem mass spectrometry (MS/MS), there are several different fragmentation techniques possible, including, collision-induced dissociation (CID) higher energy collisional dissociation (HCD), electron-capture dissociation (ECD), and electron transfer dissociation (ETD). When using pairs of spectra for de novo peptide sequencing, the most popular methods are designed for CID (or HCD) and ECD (or ETD) spectra because of the complementarity between them. Less attention has been paid to the use of CID and HCD spectra pairs. In this study, a new de novo peptide sequencing method is proposed for these spectra pairs. This method includes a CID and HCD spectra merging criterion and a parent mass correction step, along with improvements to our previously proposed algorithm for sequencing merged spectra. Three pairs of spectral datasets were used to investigate and compare the performance of the proposed method with other existing methods designed for single spectrum (HCD or CID) sequencing. Experimental results showed that full-length peptide sequencing accuracy was increased significantly by using spectra pairs in the proposed method, with the highest accuracy reaching 81.31%. PMID- 27402426 TI - Secondary immunodeficiency in lymphoproliferative malignancies. AB - Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti-inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections. The pathogenesis of immune deficiency secondary to lymphoproliferative malignancy is multifactorial including disease- and treatment related factors. Supportive treatment, including early vaccination, anti infective prophylaxis, and replacement immunoglobulin, plays a key role in preventing infections in MM and CLL. This article provides an overview of the basic immunology necessary to understand the pathogenesis of secondary immunodeficiency and the infectious complications in MM and CLL. We also discuss the evidence supporting the role of prophylactic replacement immunoglobulin treatment in patients with antibody failure secondary to MM and CLL and the indications for its use. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27402427 TI - Short (6-mm) dental implants versus sinus floor elevation and placement of longer (>=10-mm) dental implants: a randomized controlled trial with a 3-year follow-up. AB - OBJECTIVES: To investigate whether short (6-mm) dental implants could be an alternative to sinus floor elevation (SFE) and placement of longer (>=10-mm) implants in the posterior maxilla. MATERIALS AND METHODS: Over a 3-year period, all patients presenting with partial edentulism in the posterior maxilla were considered for inclusion in this randomized controlled trial. Patients were randomly chosen either to receive short (6-mm) implants (test group [TG]) or to undergo SFE with simultaneous placement of standard-length (>=10-mm) implants (control group [CG]). SFE was performed using the lateral technique. In both groups, tapered implants (AnyRidge, MegaGen, Gyeongbuk, South Korea) were placed. All implants were loaded after 4 months of healing. At each annual follow-up session, clinical and radiographic parameters were assessed. Primary outcomes were implant survival, stability (measured with the implant stability quotient [ISQ]), marginal bone loss (MBL), and complications; secondary outcomes were patient satisfaction and treatment time and cost. RESULTS: Thirty-three patients were assigned to the TG and 20 to the CG. Forty-five implants were inserted in each group. At 3 years, implant survival rates were 100% and 95.0% for the TG and CG, respectively; this difference was not statistically significant (P = 0.38). The mean ISQ values of the TG and CG did not differ at placement (68.2 vs. 67.8, P = 0.1), at delivery of the final restoration (69.5 vs. 69.4, P = 0.9), and after 1 year (71.0 vs. 71.5, P = 0.1); at 3 years, the CG had a significantly higher mean ISQ than the TG (72.4 vs. 71.6, P = 0.004). Mean MBL was significantly higher in the CG than in the TG, both at 1 year (0.14 mm vs. 0.21 mm, P = 0.006) and at 3 years (0.20 mm vs. 0.27 mm, P = 0.01). A few complications were reported. Surgical time and cost were significantly higher in the CG than in the TG (P < 0.0001). Patient satisfaction was high in both groups. CONCLUSIONS: In this randomized controlled trial, results for short (6-mm) implants were similar to those for longer (>=10-mm) implants in augmented bone. Short implants might be preferable to SFE, because the treatment is faster and less expensive. Long-term randomized controlled trials are required to confirm these results. PMID- 27402428 TI - Mark Malak. PMID- 27402430 TI - Editorial Commentary: Looking beyond the heart in adult congenital heart disease. PMID- 27402429 TI - Cloning, molecular characterization, and phylogeny of two evolutionary distinct glutamine synthetase isoforms in the green microalga Haematococcus pluvialis (Chlorophyceae). AB - Haematococcus pluvialis (Chlorophyta) is a widely used microalga of great economic potential, yet its molecular genetics and evolution are largely unknown. We present new detailed molecular and phylogenetic analysis of two glutamine synthetase (GS) enzymes and genes (gln) under the Astaxanthin-inducing conditions of light- and nitrogen-stress. Structure analysis identified key residues and confirmed two decameric GS2 holoenzymes, a cytoplasmic enzyme, termed GS2c , and a plastidic form, termed GS2p , due to chloroplast-transit peptides at its N terminus. Gene expression analysis showed dissociation of mRNA, protein, and enzyme activity levels for both GS2 under different growth conditions, indicating the strong post-transcriptional regulation. Data-mining identified novel and specified published gln genes from Prasinophyceae, Chlorophyta, Trebouxiophyceae, Charophyceae, Bryophyta, Lycopodiophyta, Spermatophyta, and Rhodophyta. Phylogenetic analysis found homologues to the cytosolic GS2c of H. pluvialis in all other photo- and non-photosynthetic Eukaryota. The chloroplastic GS2p was restricted to Chlorophyta, Bryophyta, some Proteobacteria and Fungii; no homologues were identified in Spermatophyta or other Eukaryota. This indicates two independent prokaryotic donors for these two gln genes in H. pluvialis. Combined phylogenetic analysis of GS, chl-b synthase, elongation factor, and light harvesting complex homologues project a newly refined model of Viridiplantae evolution. Herein, a GS1 evolved into the cytosolic GS2c and was passed on to all Eukaryota. Later, the chloroplastic GS2p entered the Archaeplastida lineage via a horizontal gene transfer at the divergence of Chlorophyta and Rhodophyta lineages. GS2p persisted in Chlorophyta and Bryophyta, but was lost during Spermatophyta evolution. These data suggest the revision of GS classification and nomenclature, and extend our understanding of the photosynthetic Eukaryota evolution. PMID- 27402431 TI - Regulation and role of ERK phosphorylation in glial cells following a nigrostriatal pathway injury. AB - This study was undertaken to examine the function of extracellular signal regulated kinase (ERK) signaling pathway on the proliferation and activation of microglia/macrophage and astrocytes after brain injury in mice. The result of Western blot showed that p-ERK was immediately activated after injury (<4h), but the duration was short (<4 days). According to immunofluorescence double staining, it was found that at 4 and 8h after injury, p-ERK was expressed in microglia/macrophages, and that more cells were co-expressed by p-ERK and IBA-1 (microglia/macrophage marker) at 8h; at days 1 and 4, p-ERK was expressed in astrocytes, and more cells were co-expressed by p-ERK and GFAP (astrocyte marker) at day 4. After injury, the mice were injected with U0126 (MAPK/ERK signaling pathway inhibitor) via the femoral vein. Compared with those injected with DMSO, the cell number co-expressed by p-ERK and IBA-1 or GFAP significantly decreased (P<0.05). The increase of microglia/macrophage and astrocyte caused by injury was remitted, and the positive cell number significantly decreased (P<0.05). Western blot showed that the expression quantity of IBA-1 and GFAP significantly decreased (P<0.05). Furthermore, the ERK signaling pathway was involved in the proliferation and activation of the two glial cells types and improved long-term neurobehavioral function after brain injury. Therefore, the exploration of the formation mechanism of glial scar after injury and further research on the therapeutic method of neural regeneration are essential. PMID- 27402432 TI - Memory distrust syndrome, confabulation and false confession. AB - There are three types of false confessions: 'voluntary', 'pressured-compliant' and 'pressured-internalized'. On the basis of case studies, in the early 1980s Gudjonsson and MacKeith coined the term 'memory distrust syndrome (MDS)' to describe a condition where people develop profound distrust of their memory and become susceptible to relying on external cues and suggestions from others. Memory distrust can, under certain circumstances, lead to a false confession, particularly of the pressured-internalized type, described as 'confabulation'. This article reviews the evidence for the condition and the psychological mechanism and processes involved. A heuristic model is then presented of a 32 year old man who falsely confessed to murder whilst in police custody. The key elements of the model involve the impact of 'contextual risk factors' (i.e., isolation, long and persistent guilt presumptive interrogation, and high emotional intensity) on 'enduring' vulnerability and 'acute state' factors. The detainee had kept a detailed diary whilst in solitary confinement that provided a unique insight into the gradual development of a MDS, his mental state, and thinking process. This type of false confession is apparently quite rare, but it can occur in intellectually able and educated individuals and involves 'delayed' rather than 'immediate' suggestibility. PMID- 27402433 TI - Investigating BRCA Mutations: A Breakthrough in Precision Medicine of Castration Resistant Prostate Cancer. AB - Despite the development of novel effective therapeutic strategies, metastatic castration-resistant prostate cancer (mCRPC) remains a disease with a lethal course and a high biological and molecular heterogeneity. To date, germline mutations in the BRCA gene represent one of the main risk factors for developing prostate cancer, with a strong association with aggressive phenotype and poor clinical outcomes. A better understanding of the genomic landscape of prostate cancer has strengthened the idea that "synthetic lethality" of this disease might be useful in cancer-drug discovery, focusing on agents such as platinum compounds and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). In this review, we summarize the main data available on BRCA mutations and discuss the clinical implications of these genomic aberrations in the management of prostate cancer, stressing the need to identify prognostic and predictive biomarkers and to deeply understand the mechanisms of treatment resistance, in order to maximize personalized medicine protocols and therefore clinical benefit. PMID- 27402434 TI - The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting. AB - The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti tumour necrosis factor biologics. PMID- 27402435 TI - Extended Transsphenoidal Endoscopic Endonasal Surgery of Suprasellar Craniopharyngiomas. AB - OBJECTIVE: The endoscopic extended transsphenoidal approach for suprasellar craniopharyngiomas may be a really alternative to the transcranial approach in many cases. The authors present their experience with this technique in 136 patients with craniopharyngiomas. METHODS: From the past 7 years 204 patients with different purely supradiaphragmatic tumors underwent removal by extended endoscopic transsphenoidal transtuberculum transplanum approach. Most of the patients (136) had craniopharyngiomas (suprasellar, intra-extraventricular). The patients were analyzed according to age, sex, tumor size, growth and tumor structure, and clinical symptoms. Twenty-five patients had undergone a previous surgery. The mean follow-up was 42 months (range, 4-120 months). The operation is always performed with the bilateral endoscopic endonasal anterior extended transsphenoidal approach. RESULTS: A gross-total removal was completed in 72%. Improvement of vision or absence of visual deterioration after operation was observed in 89% of patients; 11% had worsening vision after surgery. Endocrine dysfunction did not improve after surgery, new hypotalamopituitary dysfunction (anterior pituitary dysfunction or diabetes insipidus) or worsening of it was observed in 42.6%. Other main complications included transient new mental disorder in 11%, temporary neurological postoperative deficits in 3.7%, bacterial meningitis in 16%, cerebrospinal fluid leaks in 8.8%. The recurrence rate was 20% and the lethality was 5.8%. CONCLUSIONS: Resection of suprasellar craniopharyngiomas using the extended endoscopic approach is a more effective and less traumatic technology, able to provide resection of the tumor along with high quality of life after surgery, and relatively rare postoperative complications and mortality. PMID- 27402436 TI - Use of a Mobile Intraoperative Computed Tomography Scanner for Navigation Registration During Laser Interstitial Thermal Therapy of Brain Tumors. AB - OBJECTIVE: In recent years laser interstitial thermal therapy (LITT) has become the ablative neurosurgical procedure of choice. Multiple methods for registration and laser fiber verification have been described, with each method requiring multiple steps and significant time expenditure. We evaluated the use of a commercially available mobile computed tomography (CT) scanner for stereotactic registration during LITT for brain tumors in an attempt to simplify the procedure and improve intraoperative awareness of laser position. METHODS: This is a retrospective chart review comparing LITT of brain tumors in 23 patients undergoing a standard protocol requiring skull pins and transport of the patient to a CT suite to obtain a reference scan compared with 14 patients in whom the Medtronic O-arm was used intraoperatively for navigation registration and confirmation of laser position. RESULTS: Total ablation of the target was achieved in all patients with no surgical complications. Total surgery time was shorter for the O-arm group than for the standard protocol group, once experience was gained with bringing the O-arm in and out of the surgical field. Return from the magnetic resonance imaging suite to the operating room for repositioning of the laser was required for 1 patient in the standard protocol group, but for no patients in the O-arm group. Once experience was gained with using the O-arm, estimated surgical costs were lower for this group. CONCLUSIONS: Use of a mobile intraoperative CT scanner for navigation registration and confirmation of laser position during LITT may play a role in streamlining the procedure and improving patient safety and comfort. PMID- 27402437 TI - Minimally Invasive Tubular Resection of Lumbar Synovial Cysts: Report of 40 Consecutive Cases. AB - BACKGROUND: Lumbar synovial cysts are a relatively common clinical finding. Surgical treatment of symptomatic synovial cysts includes computed tomography guided aspiration, open resection and minimally invasive tubular resection. We report our series of 40 consecutive minimally invasive microscopic tubular lumbar synovial cyst resections. METHODS: Following Institutional Review Board approval, a retrospective analysis of 40 cases of minimally invasive microscopic tubular retractor synovial cyst resections at a single institution by a single surgeon (B.D.B.) was conducted. Gross total resection was performed in all cases. RESULTS: Patient characteristics, surgical operating time, complications, and outcomes were analyzed. Lumbar radiculopathy was the presenting symptoms in all but 1 patient, who presented with neurogenic claudication. The mean duration of symptoms was 6.5 months (range, 1-25 months), mean operating time was 58 minutes (range, 25-110 minutes), and mean blood loss was 20 mL (range, 5-50 mL). Seven patients required overnight observation. The median length of stay in the remaining 33 patients was 4 hours. There were 2 cerebrospinal fluid leaks repaired directly without sequelae. The mean follow-up duration was 80.7 months. Outcomes were good or excellent in 37 of the 40 patients, fair in 1 patient, and poor in 2 patients. CONCLUSIONS: Minimally invasive microscopic tubular retractor resection of lumbar synovial cysts can be done safely and with comparable outcomes and complication rates as open procedures with potentially reduced operative time, length of stay, and healthcare costs. Patient selection for microscopic tubular synovial cyst resection is based in part on the anatomy of the spine and synovial cyst and is critical when recommending minimally invasive vs. open resection to patients. PMID- 27402438 TI - Impact of Coil Packing Density and Coiling Technique on Occlusion Rates for Aneurysms Treated with Stent-Assisted Coil Embolization. AB - BACKGROUND AND OBJECTIVE: Stent-assisted coil embolization is an established endovascular technique for wide-necked intracranial aneurysms. Although recanalization after coil embolization is reduced with the use of a stent, the impact of aneurysm packing density is less clear in stent-coiled aneurysms. The purpose of the present study was to assess packing density in stent-coiled aneurysms and evaluate its effect on recanalization and retreatment. METHODS: A retrospective analysis of consecutive aneurysms treated with stent-assisted coiling was performed at 2 academic institutions between 2007 and 2015. Aneurysm occlusion was assessed using digital subtraction angiography. Packing density was calculated using the AngioCalc app. RESULTS: Two hundred fifty-three aneurysms were identified (median age, 59 years). The median packing density was 35.3%. At last follow-up, 72.7% of aneurysms were completely obliterated and 19.4% had a neck remnant. Complete occlusion was associated with smaller aneurysms and coiling through stent interstices. A higher packing density was associated with increased rate of complete occlusion when analyzed as continuous variable. After adjustment for confounding variables, packing density was no longer predictive of complete occlusion (odds ratio = 1.018, P = 0.122). Similarly, there was no significant association between aneurysm occlusion, retreatment, and packing density when assessed by categories of high (>22%), moderate (12%-22%), and low (<12%) packing density. CONCLUSIONS: Aneurysm size remains the most important predictor of aneurysm recanalization and retreatment after stent-assisted coiling. Although higher packing densities were associated with increased rates of aneurysm occlusion in unadjusted statistical comparisons, this finding was no longer significant after adjusting for confounders. PMID- 27402439 TI - Severe Pain and Edema due to a Widespread Lymphangioma: Disappearance of Symptoms and Reduction of Lesion with Spinal Cord Stimulation. AB - BACKGROUND: The efficacy of epidural spinal cord stimulation on chronic neuropathic pain due to failed back surgery syndrome or nerve root lesions is well reported. There is even literature reporting the effects of spinal cord stimulation in controlling peripheral vascular lesions as in peripheral arteriopathies or diabetic neuropathies and in complex regional pain syndrome type II. This is probably due to an effect of epidural spinal cord stimulation, mainly on the parasympathetic nervous system. CASE DESCRIPTION: A 14- year-old boy affected, since birth, by a quickly growing widespread lymphangioma at the pelvis and right thigh, underwent repetitive surgical procedures to try to reduce its extension. Recurrence always occurred. Due to a massive swelling of his right lower limb and a wide painful area all over the pelvis and right lower limb, the patient lost his autonomy and was almost bedridden or wheelchaired. On January 2015 the patient underwent the implant of a low dorsal epidural 8-lead magnetic resonance imaging (MRI)-compatible electrode connected to an MRI-compatible stimulator. The patient, 1 month after the implantation, had a complete recover of his autonomy, with a marked shrinkage of his right lower limb and a near disappearance of pain. He resumed the activity of the daily living. One year later, a hip MRI showed partial reduction of the lesion. The patient is still nearly free from pain. CONCLUSIONS: This is the first case report of severe chronic pain syndrome due to a widespread lymphangioma successfully treated by means of epidural spinal cord stimulation. PMID- 27402440 TI - Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants. AB - The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula. The economic impact of this pathogen due to livestock losses, as well as its relevance to public health, underscores the importance of developing effective and easily distributed vaccines. Vaccines that can be delivered orally are of particular interest. Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virus antigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein. Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Western blotting, respectively. Furthermore, the plant expressed antigens were evaluated for their immunogenicity in mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportion of the mice elicited specific IgG antibody responses, as compared to the control animals that were fed wild-type plants and of which none sero converted. Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virus proteins, and that the plants are immunogenic when given orally to mice. These are promising findings and provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus. PMID- 27402441 TI - Working memory of emotional stimuli: Electrophysiological characterization. AB - Memorizing emotional stimuli in a preferential way seems to be one of the adaptive strategies brought on by evolution for supporting survival. However, there is a lack of electrophysiological evidence on this bias in working memory. The present study analyzed the influence of emotion on the updating component of working memory. Behavioral and electrophysiological indices were measured from a 3-back task using negative, neutral, and positive faces. Electrophysiological data evidenced an emotional influence on the working memory sensitive P3 component, which presented larger amplitudes for negative matching faces compared to neutral ones. This effect originated in the superior parietal cortex, previously reported to be involved in N-back tasks. Additionally, P3 results showed a correlation with reaction times, where higher amplitudes were associated with faster responses for negative matching faces. These findings indicate that electrophysiological measures seem to be very suitable indices of the emotional influence on working memory. PMID- 27402442 TI - Blood levels of pro-inflammatory and anti-inflammatory cytokines in a patient with a flat glucose curve. PMID- 27402443 TI - Percutaneous closure of an unusually large patent ductus arteriosus in a patient with a giant pulmonary artery and congenital single coronary artery. PMID- 27402444 TI - Rivaroxaban for the treatment of saphenous vein graft thrombosis. AB - Thrombus formafigtion plays a significant role in disease of saphenous vein bypass grafts. Use of oral anticoagulants has not been tested in treatment of thrombotic occlusion of saphenous vein graft (SVG) disease. Here we describe the use of the novel oral anticoagulant rivaroxaban in the treatment of occlusive SVG disease with intraluminal thrombus, leading to successful recanalization. PMID- 27402445 TI - Surgery of primary malignant cardiac tumors. PMID- 27402446 TI - Combined venoarterial extracorporeal membrane oxygenation and transcatheter aortic valve implantation for the treatment of acute aortic prosthesis dysfunction in a high-risk patient. AB - We describe the case of a patient with acute bioprosthesis dysfunction in cardiogenic shock, in whom hemodynamic support was provided by venoarterial extracorporeal membrane oxygenation, and successfully treated by transcatheter aortic valve implantation. PMID- 27402447 TI - Percutaneous closure of a giant left ventricular wall pseudoaneurysm: Anterograde approach with a double snare technique. AB - Left ventricular pseudoaneurysm is a rare complication of acute myocardial infarction, cardiac surgery, trauma or infection. Since surgical repair is associated with high morbidity and mortality, percutaneous closure has been described as an alternative. In this regard, we present a case in which a symptomatic large left ventricular pseudoaneurysm was treated by percutaneous closure due to the patient's high surgical risk, using a double snare technique. Despite the technical difficulties, this procedure had a good final result followed by clinical success, confirming that this procedure is an effective alternative to surgery in high-risk patients. PMID- 27402448 TI - Conformational Change in the Active Site of Streptococcal Unsaturated Glucuronyl Hydrolase Through Site-Directed Mutagenesis at Asp-115. AB - Bacterial unsaturated glucuronyl hydrolase (UGL) degrades unsaturated disaccharides generated from mammalian extracellular matrices, glycosaminoglycans, by polysaccharide lyases. Two Asp residues, Asp-115 and Asp 175 of Streptococcus agalactiae UGL (SagUGL), are completely conserved in other bacterial UGLs, one of which (Asp-175 of SagUGL) acts as a general acid and base catalyst. The other Asp (Asp-115 of SagUGL) also affects the enzyme activity, although its role in the enzyme reaction has not been well understood. Here, we show substitution of Asp-115 in SagUGL with Asn caused a conformational change in the active site. Tertiary structures of SagUGL mutants D115N and D115N/K370S with negligible enzyme activity were determined at 2.00 and 1.79 A resolution, respectively, by X-ray crystallography. The side chain of Asn-115 is drastically shifted in both mutants owing to the interaction with several residues, including Asp-175, by formation of hydrogen bonds. This interaction between Asn-115 and Asp 175 probably prevents the mutants from triggering the enzyme reaction using Asp 175 as an acid catalyst. PMID- 27402449 TI - Identification of Miscellaneous Peptides from the Skin Secretion of the European Edible Frog, Pelophylax kl. Esculentus. AB - The chemical compounds synthesised and secreted from the dermal glands of amphibian have diverse bioactivities that play key roles in the hosts' innate immune system and in causing diverse pharmacological effects in predators that may ingest the defensive skin secretions. As new biotechnological methods have developed, increasing numbers of novel peptides with novel activities have been discovered from this source of natural compounds. In this study, a number of defensive skin secretion peptide sequences were obtained from the European edible frog, P. kl. esculentus, using a 'shotgun' cloning technique developed previously within our laboratory. Some of these sequences have been previously reported but had either obtained from other species or were isolated using different methods. Two new skin peptides are described here for the first time. Esculentin-2c and Brevinin-2Tbe belong to the Esculentin-2 and Brevinin-2 families, respectively, and both are very similar to their respective analogues but with a few amino acid differences. Further, [Asn-3, Lys-6, Phe-13] 3-14-bombesin isolated previously from the skin of the marsh frog, Rana ridibunda, was identified here in the skin of P. kl. esculentus. Studies such as this can provide a rapid elucidation of peptide and corresponding DNA sequences from unstudied species of frogs and can rapidly provide a basis for related scientific studies such as those involved in systematic or the evolution of a large diverse gene family and usage by biomedical researchers as a source of potential novel drug leads or pharmacological agents. PMID- 27402450 TI - Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T cell lymphoblastic leukaemia in complete remission. AB - CLINICAL CASE: A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. DISCUSSION: Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases. PMID- 27402451 TI - Dome shaped macula associated with myopic retinochoroidosis. Use of spironolactone. AB - CASES REPORTS: The cases are presented of three women of 22, 36 and 55 years old with bilateral myopic retinochoroidosis. They had unilateral decreased visual acuity, normal bilateral tonometry, and biomicroscopy. Funduscopy showed bilateral and unilateral myopic maculopathy, and Optical Coherence Tomography (OCT) showed a dome shaped macula with neurosensory detachment. Treatment was started with spironolactone and an improvement by OCT was shown in all cases. DISCUSSION: The etiopathogenic mechanism of the dome shaped macula is discussed. OCT demonstrated to be the fundamental test in the follow-up of this condition. After the evidence shown, initial treatment with spironolactone is suggested. PMID- 27402452 TI - Ketone production in children with type 1 diabetes, ages 4-14 years, with and without nocturnal insulin pump suspension. AB - OBJECTIVE: To compare the frequency of elevated morning blood ketone levels according to age in 4-14 year olds with type 1 diabetes following overnight use of an automated low glucose insulin suspension system, or following control nights when the system was not used. RESEARCH DESIGN AND METHODS: For 28 children ages 4-9 years and 54 youth ages 10-14 years, elevation of morning blood ketone levels was assessed using the Precision Xtra Ketone meter following 1155 and 2345 nights, respectively. Repeated measures logistic regression models were used to compare age groups for blood ketone level elevation following control nights (system not activated) and following intervention nights with and without insulin suspension. RESULTS: Elevated morning blood ketones (>=0.6 mmol/L) were present following 10% of 580 control nights in the 4-9 year olds compared with 2% of 1162 control nights in 10-14 year olds (P < 0.001). Likewise, the frequency was greater following intervention nights in the younger age group (13% of 575 nights vs 2% of 1183 nights, P < 0.001). A longer duration of pump suspension resulted in a higher percentage of mornings with elevated blood ketones in the younger age group (P = 0.002), but not in the older age group (P = 0.63). The presence of elevated morning ketone levels did not progress to ketoacidosis in any subject. CONCLUSIONS: Elevated morning blood ketones are more common in younger children with type 1 diabetes with or without nocturnal insulin suspension. Care providers need to be aware of the differences in ketogenesis in younger age children relative to various clinical situations. PMID- 27402453 TI - Should metaphase 1 and 2 stages oocytes be vitrified in the same time for fertility preservation? AB - AIMS: Could metaphase 1 (M1) and 2 (M2) stages oocytes from in vitro maturation (IVM) cycles and controlled-ovarian hyperstimulation (COH) cycles be frozen at the same time without any adverse effect of vitrification on further survival (SR) and maturation rates (MR)? MATERIALS & METHODS: M1 from cancer patients were prospectively included in IVM/COH groups, and in study or control subgroups if they were vitrified or not. In each study subgroup, SR were compared with that of M2 oocytes vitrified/warmed from egg donors. MR were compared with those of fresh M1 oocytes from control IVM/COH subgroups. RESULTS: SR were not different between groups. MR compared respectively between survived- and fresh-M1 oocytes were similar when resulting from COH (85.2 vs 81.1%) but significantly lower after IVM (39.1 vs 73.3%). CONCLUSION: Simultaneous freezing of M1/M2 oocytes could be applied to COH but not to IVM during the course of fertility preservation. PMID- 27402454 TI - Submaximal Step Tests to Estimate Maximal Oxygen Uptake in Healthy Adults: Methodological Issues About Validity and Reliability. PMID- 27402455 TI - Accelerometers for the Assessment of Concussion in Male Athletes: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Concussion is common in the sporting arena and is often challenging to diagnose. The development of wearable head impact measurement systems has enabled measurement of head kinematics in contact sports. OBJECTIVES: The objective of this systematic review was to determine the characteristics of head kinematics measured by an accelerometer system among male athletes diagnosed with concussion. METHODS: A systematic search was conducted in July 2015. Inclusion criteria were English-language studies published after 1990 with a study population of male athletes, in any sport, where objectively measured biomechanical forces were reported in the setting of a concussive event. The random effects meta-analysis model was used to combine estimates of biomechanical force measurements in concussed athletes. RESULTS: Thirteen studies met the inclusion criteria, the majority of which were conducted with high school and college football teams in the US. Included studies measured a combination of linear and rotational acceleration. The meta-analysed mean peak linear head acceleration associated with a concussive episode was 98.68 g (95 % CI 82.36 115.00) and mean peak rotational head acceleration was 5776.60 rads/s2 (95 % CI 4583.53-6969.67). The estimates of the biomechanical forces were consistent across studies, with I 2 values of 0 % for both meta-analyses. CONCLUSIONS: Head impact monitoring through accelerometery has been shown to be useful with regard to characterising the kinematic load to the head associated with concussion. Future research with improved clinical outcome measures and head kinematic data may improve accuracy when evaluating concussion, and may assist with both interpretation of biomechanical data and the development and utilisation of implementation strategies for the technology. PMID- 27402456 TI - A Review of Emerging Analytical Techniques for Objective Physical Activity Measurement in Humans. AB - Physical inactivity is one of the most prevalent risk factors for non communicable diseases in the world. A fundamental barrier to enhancing physical activity levels and decreasing sedentary behavior is limited by our understanding of associated measurement and analytical techniques. The number of analytical techniques for physical activity measurement has grown significantly, and although emerging techniques may advance analyses, little consensus is presently available and further synthesis is therefore required. The objective of this review was to identify the accuracy of emerging analytical techniques used for physical activity measurement in humans. We conducted a search of electronic databases using Web of Science, PubMed, and Google Scholar. This review included studies written in English and published between January 2010 and December 2014 that assessed physical activity using emerging analytical techniques and reported technique accuracy. A total of 2064 papers were initially retrieved from three databases. After duplicates were removed and remaining articles screened, 50 full text articles were reviewed, resulting in the inclusion of 11 articles that met the eligibility criteria. Despite the diverse nature and the range in accuracy associated with some of the analytic techniques, the rapid development of analytics has demonstrated that more sensitive information about physical activity may be attained. However, further refinement of these techniques is needed. PMID- 27402458 TI - A novel bacterial type II l-asparaginase and evaluation of its enzymatic acrylamide reduction in French fries. AB - This study reports the identification of a novel bacterial type II l asparaginase, abASNase2, from Aquabacterium sp. A7-Y. The enzyme contains 319 amino acids and shared 35% identity with Escherichia coli type II l-asparaginase (EcAII), a commercial enzyme trademarked Elspar(r) that is widely used for medical applications. abASNase2 had high specific activity (458.9U/mg) toward l asparagine, very low activity toward l-glutamine and d-glutamine and no activity toward d-asparagine. The optimal enzymatic activity conditions for abASNase2 were found to be 50mM Tris-HCl buffer (pH 9.0) at 60 degrees C. It was very stable in the pH range of 7.0-11.0 and exhibited up to 80% relative activity after 2h below 40 degrees C. The Km and kcat of abASNase2 were 1.8*10-3M and 241.9s-1, respectively. In addition, abASNase2's ability to remove acrylamide from fried potato strips was evaluated. Compared to untreated potato strips (acrylamide content: 0.823+/-0.0457mg/kg), 88.2% acrylamide was removed in the abASNase2 treated group (acrylamide content: 0.097+/-0.0157mg/kg). These results indicate that the novel l-asparaginase abASNase2 is a potential candidate for applications in the food processing industry. PMID- 27402457 TI - Should Return to Sport be Delayed Until 2 Years After Anterior Cruciate Ligament Reconstruction? Biological and Functional Considerations. AB - Anterior cruciate ligament (ACL) tears are common knee injuries sustained by athletes during sports participation. A devastating complication of returning to sport following ACL reconstruction (ACLR) is a second ACL injury. Strong evidence now indicates that younger, more active athletes are at particularly high risk for a second ACL injury, and this risk is greatest within the first 2 years following ACLR. Nearly one-third of the younger cohort that resumes sports participation will sustain a second ACL injury within the first 2 years after ACLR. The evidence indicates that the risk of second injury may abate over this time period. The incidence rate of second injuries in the first year after ACLR is significantly greater than the rate in the second year. The lower relative risk in the second year may be related to athletes achieving baseline joint health and function well after the current expected timeline (6-12 months) to be released to unrestricted activity. This highlights a considerable debate in the return to sport decision process as to whether an athlete should wait until 2 years after ACLR to return to unrestricted sports activity. In this review, we present evidence in the literature that athletes achieve baseline joint health and function approximately 2 years after ACLR. We postulate that delay in returning to sports for nearly 2 years will significantly reduce the incidence of second ACL injuries. PMID- 27402459 TI - Interaction of stem cells with nano hydroxyapatite-fucoidan bionanocomposites for bone tissue regeneration. AB - The combination of bioceramics with biopolymers are playing major role in the construction of artificial bone. Hydroxyapatite (HA) has been extensively studied as a material in bone repair and replacement in last two decades. In the present study, we have prepared the hydroxyapatite-fucoidan (HA-Fucoidan) nanocomposites by in situ chemical method and biologically characterized them for bone graft substitute. Biological results inferred that mineralization effect of HA-F nanocomposites shows significant enhancement compared to HA in adipose derived stem cell (ADSC). It may be due to the addition of fucoidan in the nanocomposites. The important gene expression such as osteocalcin, osteopontin, collagen and runx-2 were checked using ADSC with HA and HA-fucoidan nanocomposites and the results show that the enhancements were found at 7th day. Furthermore, we have performed in vivo study of HA-fucoidan nanocomposites with rabbit model and a slight amount of bone formation was observed in HA-fucoidan nanocomposites. Herewith, we suggest that HA-fucoidan nanocomposites will be good biomaterials for bone repair/replacement in future. PMID- 27402460 TI - Multi-scale structural changes of starch-based material during microwave and conventional heating. AB - This work revealed the influence of thermal processing on the microstructural, mesoscopic and molecular scale structures and thus the plasticizer migration of the starch ester films. Thermal processing promoted the permeation of water molecules to hinder the shrink of the amorphous macromolecules. That is, the swelling of the amorphous macromolecules diminished the ordered regions to a certain degree, resulting in the enlarged amorphous regions. Along with slight degradation of the macromolecules, the crystallites were partially disorganized, as indicated by a reduced relative crystallinity. These multi-scale structural changes of the films and the thermally enhanced mobility of plasticizer molecules synergistically enhanced the plasticizer migration. This study not only enables a well understanding of how thermal treatment alters the plasticizer migration of starch-based films from a multi-scale structural view, but also hints to our future work that rationally modulating the structural features of starch-based film may effectively control the migration of chemicals. PMID- 27402462 TI - Treatment of sewage sludge in a continuous-flow radiofrequency-oxidation system. AB - This study explored the applicability of a pilot-scale continuous-flow radiofrequency (RF) heating system to treat sewage sludge by the RF-oxidation process (RF/H2O2). Depending on temperature and hydrogen peroxide dosage, high amounts of soluble chemical oxygen demand and volatile fatty acid were produced, and phosphates, nitrogen, and metals were solubilized. A high temperature and/or a higher H2O2 dosage implemented in this system yielded high solubilization of organic matters. Orthophosphate increased with an increase in treatment temperature up to 60 degrees C, its concentration decreased as temperature further increased. There was little effect on orthophosphate release by varying H2O2 dosage. The efficiency of the RF/H2O2 process was comparable to the microwave (MW) enhanced advanced oxidation process (MW/H2O2-AOP), in terms of solids disintegration and nutrient release; however, the solubilization rate was lower for RF/H2O2 process. The overall energy consumed by the RF/H2O2 process was higher than the MW/H2O2-AOP. PMID- 27402461 TI - A parallel panning scheme used for selection of a GluA4-specific Fab targeting the ligand-binding domain. AB - A method for development of murine Fab fragments towards extracellular domains of a surface receptor is presented. The GluA4 ionotropic glutamate receptor is used as a model system. Recombinant GluA4 ectodomain comprising both the N-terminal domain (NTD) and the ligand-binding domain (LBD) in one molecule was used for immunization. A Fab-phage library was constructed and a parallel panning approach enabled selection of murine Fab fragments towards either intact ectodomain or the isolated LBD of the GluA4 receptor. One LBD-Fab (FabL9) showed exclusive selectivity for the GluA4 LBD, over a panel of LBDs from GluA2, GluK1, GluK2 and GluD2. Soluble FabL9 was produced in amounts suitable for characterization. Competitive ELISA and rat-brain immunoprecipitation experiments confirmed that the FabL9 epitope is conserved in the LBD and in the intact native receptor. By an alignment of GluA2 and GluA4, the likely binding epitope for FabL9 was predicted. This study demonstrates a simple approach for development of antibody fragments towards specific sub-domains of a large ligand-gated ion channel, and this method could be utilized for all multi-domain surface receptors where antibody domain-selectivity may be desirable. Furthermore, we present for the first time a GluA4 subtype-specific murine Fab fragment targeting the LBD of the receptor. PMID- 27402463 TI - Unravelling the mechanisms of reactive oxygen species formation in nanohybrid systems of porphyrins and enriched (6,5) single-walled carbon nanotubes for photosensitization. AB - Nanohybrids of enriched (6,5) single-walled semiconducting carbon nanotubes (E SWCNTs) and porphyrin can be used synergistically as photodynamic therapy (PDT) agents. The efficiency of different porphyrins within the nanohybrids was investigated and compared with results obtained from porphyrins in previous studies. Reactive oxygen species singlet oxygen (1)O2 and for the first time hydroxyl radical OH generation by the nanohybrids under illumination were detected by electron paramagnetic resonance using spin trapping molecules TEMP and PBN. Based on the analysis, we improve the modelling of charge transport within the nanohybrids, which is also detected by Raman scattering. It is shown that the 5,10,15,20-tetrakis(4-trimethylammoniumphenyl)porphyrin [H2TTMAPP(OTs)4] and E-SWCNT form very efficient nanohybrids for PDT applications in the visible spectral range. PMID- 27402464 TI - A protocol for staged arthroplasty to salvage infected nonunion of hip fractures. AB - BACKGROUND: Nonunion of hip fractures is not uncommon. Total hip arthroplasty is used to salvage cases of non union or secondary arthritis in these fractures. However, this option may not be available or may be difficult to achieve when infection has superseded the site of nonunion. The objective of this prospective study was to assess if a staged protocol of treatment yields good results in these difficult cases. MATERIALS AND METHODS: Twenty-seven consecutive patients who had deep hip infection with failed treatment of hip fractures (intracapsular in 16 cases and extracapsular in 11) were treated between June 2007 and September 2011. Twenty-six completed the planned two-stage hip arthroplasty and one case was lost after the first stage. The average age of the patients was 48.9 years (range 26-74 years) with an average follow up period of 44 months (30-72 months). Analysis was done using the paired t test where P < 0.05 was considered significant. RESULTS: Infection was controlled in all cases that completed the treatment protocol with no recurrence in all cases at the latest follow up. The Harris hip score of the patients improved significantly from 29 preoperatively to 85 at the latest follow up (P < 0.0001). Two patients had hip dislocation with displacement of the trochanteric fragment while three other patients had fibrous union of the trochanter. CONCLUSIONS: Staged Arthroplasty procedure to salvage infected non-union of hip fractures is successful in eradicating infection and regaining hip function. Level of evidence IV. PMID- 27402465 TI - Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9. AB - PURPOSE: The study aims to determine the possible effects of black tea consumption on the level of CA 19-9 antigen in the human body. METHODS: The level of CA 19-9 was measured in 270 healthy individuals who consumed heavy amounts of black tea. RESULTS: About 43.3 % of involved individuals were revealed to have elevated levels of CA 19-9. Males with high values of CA 19-9 represented the greatest number of involved individuals. The cutoff value of high levels of CA 19 9 in all individuals was ranged 69-105 U/ml. CONCLUSIONS: Consuming heavy amounts of black tea could be considered an important interfering factor that affects the levels of CA 19-9. The cutoff or predictive value of CA 19-9 in heavy-consuming people of black tea was determined. PMID- 27402466 TI - A randomised comparative study of 1064 nm Neodymium-doped yttrium aluminium garnet (Nd:YAG) laser and topical antifungal treatment of onychomycosis. AB - Conventional treatments for onychomycosis include oral and topical antifungal agents. Although Nd:YAG laser has been reported to be effective, controlled studies combined or compared with conventional treatments are needed. To evaluate the efficacy of 1064 nm Nd:YAG laser for onychomycosis and compare outcomes with those of topical antifungal treatment and combination therapy. Patients were randomly divided into three groups: Laser (L); laser with topical antifungal therapy (L + T); and topical antifungal treatment (T). Laser treatment consisted of three or four sessions at 4 week intervals. Outcomes were assessed clinically and mycologically. In 217 nails of 56 patients, 76% in the L group and 71.8% in the L + T group experienced clinical responses, and 15.2% and 22.5%, respectively, were cured at 24 weeks. The clinical and cure rates of both groups were significantly greater than those of the T group. Six patients of the L group developed new infections, as did one patient in the L + T group and two patients in the T group. 1064 nm Nd:YAG laser shows clinically good responses in onychomycosis. Addition of topical antifungal agent did not appear to improve efficacy, but may have protected against new infection. PMID- 27402467 TI - WITHDRAWN: Special focus: Expanding access to care and treatment for hepatitis C virus infection among people who inject drugs. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27402468 TI - Coca cultivation and crop eradication in Colombia: The challenges of integrating rural reality into effective anti-drug policy. AB - This paper examines the positive and negative (or intended and unintended) impacts of anti-drug policies such as the aerial spraying of coca crops in Colombia. It provides spatial analysis of coca cultivation and crop eradication at a fine scale of resolution using the latest UNODC data. The findings suggest that anti-drug policy in Colombia between 2001 and 2012 has had some success with a significant decrease in overall levels of coca cultivation, but that it has also led to the displacement of coca cultivation, notably to areas within the Colombian Pacific region. Negative impacts include continued deforestation and damage to ecosystems, and the further marginalization of Afro-Colombian communities whose collective territories have been subject to increased coca cultivation between 2001 and 2012. Alternative development programs have not been well aligned with such areas where other illegal activities such as mining as well as coca cultivation now occur. Hence the importance of designing anti-drug policy that comprehensively integrates the local nuances of those peoples and places affected by coca cultivation and crop eradication according to their particular contexts. PMID- 27402469 TI - Illicit drug overdose deaths resulting from income assistance payments: Analysis of the 'check effect' using daily mortality data. AB - BACKGROUND: Although income assistance is an important source of support for low income individuals, there is evidence that adverse outcomes may increase when payments are disbursed on the same day for all recipients. The objective of this study was to assess the temporal patterns and causal relation between population level illicit drug overdose deaths and income assistance payments using daily mortality data for British Columbia over a period of five years. METHODS: Retrospective data on daily mortality due to illicit drug overdose, 2009-2013, were provided by the BC Coroners Service. These data were analyzed using regression models and time series tests for causality in relation to dates of income assistance payments. RESULTS: 1343 deaths due to illicit drug overdose were reported in BC during 2009-2013; 394 occurred during cheque weeks (n=60) and 949 occurred during non-cheque weeks (n=202). Average weekly mortality due to illicit drug overdose was 40% higher during weeks of income assistance payments compared to weeks without payments (P<0.001). Consistent increases in mortality appeared the day after cheque disbursement and were significantly higher for two days, and marginally higher after 3 days, even when controlling for other temporal trends. Granger causality testing suggests the timing of cheque issue was causally linked to increased drug overdose mortality (P<0.001). CONCLUSIONS: Our findings clarify the temporal relation and causal impact of income assistance payments on illicit drug deaths. We estimate 77 avoidable deaths were attributable to the synchronized disbursement of income assistance cheques over the five year period. An important consideration is whether varying the timing of payments among recipients could reduce this excess mortality and the related demands on health and social services. PMID- 27402470 TI - Toward Refinement of Our Understanding of the Fundamental Nature of Addiction. PMID- 27402471 TI - A Need for Longitudinal Studies in the Addiction Field. PMID- 27402472 TI - Astrocytes: The Stars of Extinction-Related Learning or Cocaine-Induced Brain Plasticity? PMID- 27402473 TI - Treating Addiction: Unraveling the Relationship Between N-acetylcysteine, Glial Glutamate Transport, and Behavior. PMID- 27402474 TI - Association of alcohol consumption with coronary artery disease severity. AB - BACKGROUND & AIMS: The ingestion of small to moderate alcohol consumption amounts has been associated to cardiovascular protection. This study aimed to evaluate the association between alcohol consumption and coronary artery disease severity. MATERIAL AND METHODS: Cross-sectional Study with patients undergoing coronary angiography. Age, cardiovascular risk factors (smoking, systemic arterial hypertension, dyslipidemia and diabetes) and alcohol drinking habit were investigated. Alcohol consumption was divided in three categories: nondrinker, moderate alcohol consumption (less than 15 g ethanol/day for women or 30 g ethanol/day for men) and heavy alcohol consumption. Coronary artery disease severity was assessed through the Friesinger Score (FS) in the coronary angiography, by interventional cardiologists blinded to alcohol consumption. RESULTS: The final sample included 363 adults; of those, 228 were men (62.81%). Mean age was 60.5 +/- 10.9 y. Unadjusted analyses identified sex, age, hypertension, diabetes, dyslipidemia and alcohol consumption as the main covariates associated with the Friesinger score. Lower Friesinger scores were also observed in moderate alcohol consumption when comparing to those who do not drink (RR 0.86; 95% CI 0.79-0.95). CONCLUSION: Among patients with suspected coronary artery disease undergoing coronary angiography, moderate alcohol consumption is associated to a lower coronary artery disease severity than heavy drinking. PMID- 27402476 TI - An image-guided automated robot for MRI breast biopsy. AB - BACKGROUND: The IGAR (Image-guided Automated Robot) is a robotic platform capable of performing highly accurate clinical interventions under image guidance. The IGAR is unique in that it demonstrates MRI compatibility and maintains safe operation, adequate shielding, high image quality, and accurate robotic control even while in an imaging environment. The IGAR is initially intended for breast biopsy. METHODS: Tests for projectile hazards, heating, signal-to-noise ratio loss, and geometric distortion were used to demonstrate MR compatibility. Accuracy and repeatability of the robotic system were tested on benchtop models to establish a baseline of precision. RESULTS: The IGAR averaged an accuracy of 0.34 mm and a repeatability of 0.2 mm. There was no significant distortion attributable to the robot, no projectile risk, and no unacceptable levels of heating. CONCLUSION: The IGAR system is safe and effective in an MRI environment Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27402475 TI - High-dose vitamin D3 reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults. AB - BACKGROUND & AIMS: In vitro studies suggest that vitamin D may reduce hepcidin expression and pro-inflammatory cytokine release from monocytes. However, data assessing the vitamin D-mediated effects on iron recycling in healthy individuals are lacking. We aimed to examine the effect of high-dose vitamin D3 on plasma hepcidin, inflammatory cytokine, and ferritin concentrations in healthy adults. METHODS: This was a pilot, double-blind, placebo-controlled trial in healthy adults (N = 28) randomized to receive a one-time oral dose of 250,000 IU of vitamin D3 or placebo. Between- and within-group differences in plasma hepcidin, pro-inflammatory cytokine [interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1)], and ferritin concentrations at baseline and 1 week were determined using two-sample and paired t-tests, respectively. RESULTS: At baseline, plasma 25-hydroxyvitamin D [25(OH)D], hepcidin, pro-inflammatory cytokine, and ferritin concentrations did not differ between the two groups, and greater than 70% of subjects in both groups were vitamin D deficient (25(OH)D < 20 ng/mL). After 1 week, plasma hepcidin concentrations decreased by 73% from baseline in those who received vitamin D3 (geometric mean ratio [GMR] = 0.27 (95% CI: 0.11-0.62); P = 0.005); there was no significant change in the placebo group (GMR = 0.73 (95% CI: 0.49-1.09); P = 0.11). Plasma cytokine and ferritin concentrations did not change significantly in either group. CONCLUSIONS: High dose vitamin D3 significantly reduced plasma hepcidin concentrations in healthy adults 1 week post-dosing, without a change in plasma pro-inflammatory cytokine or ferritin concentrations. These data suggest that vitamin D may have a role in regulating iron recycling by acting independently of changes in pro-inflammatory markers. PMID- 27402477 TI - Mitochondrial DNA mutations in blood samples from HIV-1-infected children undergoing long-term antiretroviral therapy. AB - We have analyzed mutations in whole mitochondrial (mt) genomes of blood samples from HIV-1-infected children treated with long-term antiretroviral therapy (ART), who had an excellent virological response. HIV-1-infected children who have undergone ART for 4 y with an excellent virological response (group A; 15 children) and ten healthy children (controls) without HIV-1 infection were enrolled retrospectively. Peripheral blood mononuclear cells (PBMCs) were obtained and mt DNA mutations were studied. The total number of mtDNA mutations in group A was 3 H more than in the controls (59 vs. 19, P<0.001) and the same trend was seen in all mtDNA regions. Among these mtDNA mutations, 140 and 28 mutations were detected in group A and the controls, respectively. The D-loop, CYTB and 12s rRNA were the three most common mutation regions in both groups, with significant differences between the groups observed at nucleotide positions C309CC, T489C CA514deletion, T16249C and G16474GG (D-loop); T14783C, G15043A, G15301A, and A15662G (CYTB); and G709A (12s rRNA). G15043A and A15662G had been associated with mitochondrial diseases. Our findings suggest that mtDNA mutations occur frequently in long-term ART-treated, HIV-1-infected children who have an excellent virological response, although they did not have obvious current symptoms. The CYTB region may play an important role in mtDNA mutation during ART, which might contribute to the development of subsequent mitochondrial diseases. PMID- 27402478 TI - Effect of particle size and dispersion status on cytotoxicity and genotoxicity of zinc oxide in human bronchial epithelial cells. AB - Data available on the genotoxicity of zinc oxide (ZnO) nanoparticles (NPs) are controversial. Here, we examined the effects of particle size and dispersion status on the cytotoxicity and genotoxicity of nanosized and fine ZnO, in the presence and absence of bovine serum albumin (BSA; 0.06%) in human bronchial epithelial BEAS-2B cells. Dynamic light scattering analysis showed the most homogenous dispersions in water alone for nanosized ZnO and in water with BSA for fine ZnO. After a 48-h treatment, both types of ZnO were cytotoxic within a similar, narrow dose range (1.5-3.0MUg/cm(2)) and induced micronuclei at a near toxic dose range (1.25-1.75MUg/cm(2)), both with and without BSA. In the comet assay, nanosized ZnO (1.25-1.5MUg/cm(2)), in the absence of BSA, caused a statistically significant increase in DNA damage after 3-h and 6-h treatments, while fine ZnO did not. Our findings may be explained by better uptake or faster intracellular dissolution of nanosized ZnO without BSA during short treatments (3 6h; the comet assay), with less differences between the two ZnO forms after longer treatments (>48h; the in vitro micronucleus test). As ZnO is genotoxic within a narrow dose range partly overlapping with cytotoxic doses, small experimental differences e.g. in the dispersion of ZnO particles may have a substantial effect on the genotoxicity of the nominal doses added to the cell culture. PMID- 27402480 TI - The EpiDermTM 3D human reconstructed skin micronucleus (RSMN) assay: Historical control data and proof of principle studies for mechanistic assay adaptations. AB - The in vitro human reconstructed skin micronucleus (RSMN) assay in EpiDermTM is a promising novel animal alternative for evaluating genotoxicity of topically applied chemicals. It is particularly useful for assessing cosmetic ingredients that can no longer be tested using in vivo assays. To advance the use of this test especially for regulatory decision-making, we have established the RSMN assay in our laboratory according to Good Laboratory Practice and following the principles of the OECD test guideline 487 in vitro mammalian cell micronucleus test. Proficiency with the assay was established by correctly identifying direct acting genotoxins and genotoxins requiring metabolism, as well as non genotoxic/non-carcinogenic chemicals. We also report the analysis of our historical control data that demonstrate vehicle control and positive control values for %micronuclei in binucleated cells are in the ranges reported previously. Technical issues including evaluating various solvents with both 48h and 72h treatment regimens were investigated. For the first time, mechanistic studies using CREST analysis revealed that the RSMN assay is suitable for distinguishing aneugens and clastogens. Moreover, the assay is also suitable for measuring cytokines as markers for proliferative and toxic effects of chemicals. PMID- 27402479 TI - 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice. AB - The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4 aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy. PMID- 27402481 TI - Quantification of the mutagenic potency and repair of glycidol-induced DNA lesions. AB - Glycidol (Gly) is an electrophilic low-molecular weight epoxide that is classified by IARC as probably carcinogenic to humans. Humans might be exposed to Gly from food, e.g. refined vegetable oils, where Gly has been found as a food process contaminant. It is therefore important to investigate and quantify the genotoxicity of Gly as a primary step towards cancer risk assessment of the human exposure. Here, quantification of the mutagenic potency expressed per dose (AUC: area under the concentration-time curve) of Gly has been performed in Chinese hamster ovary (CHO) cells, using the HPRT assay. The dose of Gly was estimated in the cell exposure medium by trapping Gly with a strong nucleophile, cob(I)alamin, to form stable cobalamin adducts for analysis by LC-MS/MS. Gly was stable in the exposure medium during the time for cell treatment, and thus the dose in vitro is the initial concentration*cell treatment time. Gly induced mutations in the hprt gene at a rate of 0.08+/-0.01 mutations/10(5) cells/mMh. Through comparison with the effect of ionizing radiation in the same system a relative mutagenic potency of 9.5rad-eq./mMh was obtained, which could be used for comparison of genotoxicity of chemicals and between test systems and also in procedures for quantitative cancer risk assessment. Gly was shown to induce strand breaks, that were repaired by base excision repair. Furthermore, Gly-induced lesions, present during replication, were found to delay the replication fork elongation. From experiments with repair deficient cells, homologous recombination repair and the ERCC1-XPF complex were indicated to be recruited to support in the repair of the damage related to the stalled replication elongation. The type of DNA damage responsible for the mutagenic effect of Gly could not be concluded from the present study. PMID- 27402482 TI - Toxic and DNA damaging effects of a functionalized fullerene in human embryonic lung fibroblasts. AB - Water-soluble fullerenes have been studied as potential nanovectors and therapeutic agents, but their possible toxicity is of concern. We have studied the effects of F-828, a soluble fullerene [C60] derivative, on diploid human embryonic lung fibroblasts (HELFs) in vitro. F-828 causes complex time-dependent changes in ROS levels. Inhibition of Nox4 activity by plumbagin blocks F-828 dependent ROS elevation. F-828 induces DNA breaks, as measured by the comet assay and gammaH2AX expression, and the activities of the transcription factors NF-kB and p53 increase. F-828 concentrations>25MUM are cytotoxic; cell death occurs by necrosis. Expression levels of TGF-beta, RHOA, RHOC, ROCK1, and SMAD2 increase following exposure to F-828. Our results raise the possibility that fullerene F 828 may induce pulmonary fibrosis in vivo. PMID- 27402483 TI - Erratum to: Comparison of the topical haemostatic efficacy of nano-micro particles of clinoptilolite and kaolin in a rat model of haemorrhagic injury. PMID- 27402484 TI - The use of Reamer-irrigator-aspirator in the management of long bone osteomyelitis: an update. AB - PURPOSE: Reamer-irrigator-aspirator (RIA) is an innovative device that its indications have recently been expanded to the management of long bone infections. METHODS: In this narrative review, we summarise the most important studies in the field and we present the current open questions pertaining to the use of RIA in the management of osteomyelitis of long bones. RESULTS: The relevant literature is sparse and low quality. Nevertheless, the use of RIA for infected cases has yielded promising outcomes in specialised centres. Technical aspects that merit special attention in osteomyelitis of long bones are its inapplicability in small diameter long bones, the inadequate debridement of wide metaphyseal areas and the potential bleeding sequelae. The use of RIA in open fracture management to reduce infection risk has not gained acceptance. The antibiotic impregnated nails and rods constitute a complimentary strategy for the management of infections. CONCLUSIONS: The use of RIA for the management of long bone infections is an innovative and promising strategy. High quality studies are needed to shed light in its efficacy compared to conventional methods of management of osteomyelitis of long bones. PMID- 27402486 TI - Primary sclerosing cholangitis: 50 years of a gut-liver relationship and still no love? PMID- 27402485 TI - Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. AB - BACKGROUND: Pancreatic cancer is characterised by the accumulation of a fibro inflammatory stroma. Within this stromal reaction, myeloid cells are a predominant population. Distinct myeloid subsets have been correlated with tumour promotion and unmasking of anti-tumour immunity. OBJECTIVE: The goal of this study was to determine the effect of myeloid cell depletion on the onset and progression of pancreatic cancer and to understand the relationship between myeloid cells and T cell-mediated immunity within the pancreatic cancer microenvironment. METHODS: Primary mouse pancreatic cancer cells were transplanted into CD11b-diphtheria toxin receptor (DTR) mice. Alternatively, the iKras* mouse model of pancreatic cancer was crossed into CD11b-DTR mice. CD11b+ cells (mostly myeloid cell population) were depleted by diphtheria toxin treatment during tumour initiation or in established tumours. RESULTS: Depletion of myeloid cells prevented KrasG12D-driven pancreatic cancer initiation. In pre established tumours, myeloid cell depletion arrested tumour growth and in some cases, induced tumour regressions that were dependent on CD8+ T cells. We found that myeloid cells inhibited CD8+ T-cell anti-tumour activity by inducing the expression of programmed cell death-ligand 1 (PD-L1) in tumour cells in an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinases (MAPK) dependent manner. CONCLUSION: Our results show that myeloid cells support immune evasion in pancreatic cancer through EGFR/MAPK-dependent regulation of PD-L1 expression on tumour cells. Derailing this crosstalk between myeloid cells and tumour cells is sufficient to restore anti-tumour immunity mediated by CD8+ T cells, a finding with implications for the design of immune therapies for pancreatic cancer. PMID- 27402488 TI - Development and Comparison of TaqMan-Based Real-Time PCR Assays for Detection and Differentiation of Ralstonia solanacearum strains. AB - Bacterial wilt caused by Ralstonia solanacearum is destructive to many plant species worldwide. The race 3 biovar 2 (r3b2) strains of R. solanacearum infect potatoes in temperate climates and are listed as select agents by the U.S. government. TaqMan-based real-time quantitative PCR (qPCR) is commonly used in federal and state diagnostic laboratories over conventional PCR due to its speed and sensitivity. We developed the Rs16S primers and probe set and compared it with a widely used set (RS) for detecting R. solanacearum species complex strains. We also developed the RsSA3 primers and probe set and compared it with the previously published B2 and RsSA2 sets for specific detection of r3b2 strains. Both comparisons were done under standardized qPCR master mix and cycling conditions. The Rs16S and RS assays detected all 90 R. solanacearum species complex strains and none of the five outgroups, but the former was more sensitive than the latter. For r3b2 strain detection, the RsSA2 and RsSA3 sets specifically detected the 34 r3b2 strains and none of the 56 R. solanacearum non r3b2 strains or out-group strains. The B2 set, however, detected five non-r3b2 R. solanacearum strains and was less sensitive than the other two sets under the same testing conditions. We conclude that the Rs16S, RsSA2, and RsSA3 sets are best suited under the standardized conditions for the detection of R. solanacearum species complex and r3b2 strains by TaqMan-based qPCR assays. PMID- 27402489 TI - While-you-wait proteins? Producing biomolecules at the point of need. PMID- 27402487 TI - Oral Bioavailability and Mass Balance Studies of a Novel Anti-arrhythmic Agent Sulcardine Sulfate in Sprague-Dawley Rats and Beagle Dogs. AB - BACKGROUND AND OBJECTIVES: Sulcardine sulfate is a newly developed candidate drug used to control arrhythmias. The aim of this research was to investigate the pharmacokinetics, bioavailability and excretion characteristics of sulcardine in animals. METHODS: Sprague-Dawley rats were orally and intravenously given sulcardine at 20 and 40 mg/kg. Beagle dogs were also orally and intravenously dosed at 10 mg/kg. Both [3H]-labeled sulcardine and unlabeled sulcardine were given to rats. Feces, urine and bile were collected at 0-72 h for mass balance study. The contents of unlabeled sulcardine and radioactivity in samples were determined by a validated LC-MS/MS method and by liquid scintillation counting, separately. RESULTS: Sulcardine was rapidly eliminated in rats after dosing. The oral bioavailability was 34-35 % in rats, while a higher exposure was observed in dogs (bioavailability = 62.7 %). More than 90 % of dosed sulcardine was recovered, and approximately 20-40 % of the dose excreted into urine as the original form, and the remaining was found in feces and bile, most of which (about 40 %) was transformed into metabolites. No difference was observed between sexes. Metabolism may occur to a large extent after oral administration in rats but to a smaller extent in dogs. CONCLUSIONS: Sulcardine was extensively absorbed in both rats and dogs after oral administration. The mass balance data indicated that sulcardine was widely metabolized in rats after oral administration. PMID- 27402490 TI - Sirtuins as modifiers of Parkinson's disease pathology. AB - Parkinson's disease (PD) is the most common movement disorder associated with the elderly which, other than symptomatic therapies, has no effective treatment or preventive measures. Sirtuins and their pharmacological activators/inhibitors have been associated with a range of neuroprotective effects, and a large body of work on sirtuins' influence on PD pathology has accumulated over the past decade. Here, evidence for sirtuins' activities as modifiers of PD pathology and how the mammalian sirtuin paralogues may have conflicting impacts on PD pathogenesis and disease progression is reviewed. The possible cellular and molecular mechanisms underlying sirtuin activities in PD are discussed in the light of current knowledge with reference to autophagy, mitochondrial homeostasis, and microtubule dynamics. (c) 2016 Wiley Periodicals, Inc. PMID- 27402491 TI - Clinical Profile of Arrhythmogenic Right Ventricular Cardiomyopathy With Left Ventricular Involvement. PMID- 27402492 TI - What Should We Target in Heart Failure: Hemoglobin or Iron? PMID- 27402493 TI - Takayasu Arteritis Presenting as Acute Pericarditis. PMID- 27402497 TI - A simple microfluidic device to study cell-scale endothelial mechanotransduction. AB - Atherosclerosis is triggered by chronic inflammation of arterial endothelial cells (ECs). Because atherosclerosis develops preferentially in regions where blood flow is disturbed and where ECs have a cuboidal morphology, the interplay between EC shape and mechanotransduction events is of primary interest. In this work we present a simple microfluidic device to study relationships between cell shape and EC response to fluid shear stress. Adhesive micropatterns are used to non-invasively control EC elongation and orientation at both the monolayer and single cell levels. The micropatterned substrate is coupled to a microfluidic chamber that allows precise control of the flow field, high-resolution live-cell imaging during flow experiments, and in situ immunostaining. Using micro particle image velocimetry, we show that cells within the chamber alter the local flow field so that the shear stress on the cell surface is significantly higher than the wall shear stress in regions containing no cells. In response to flow, we observe the formation of lamellipodia in the downstream portion of the EC and cell retraction in the upstream portion. We quantify flow-induced calcium mobilization at the single cell level for cells cultured on unpatterned surfaces or on adhesive lines oriented either parallel or orthogonal to the flow. Finally, we demonstrate flow-induced intracellular calcium waves and show that the direction of propagation of these waves is determined by cell polarization rather than by the flow direction. The combined versatility and simplicity of this microfluidic device renders it very useful for studying relationships between EC shape and mechanosensitivity. PMID- 27402496 TI - Central Nervous System: (Immunological) Ivory Tower or Not? AB - The view of the nervous system being the victim of destructive inflammation during autoimmunity, degeneration, or injury has been rapidly changing. Recent studies are supporting the idea that the immune system provides support for the nervous system at various levels. Though cell patrolling through the nervous system parenchyma is limited compared with other tissues, immune cell presence within the central nervous system (CNS; microglia), as well as around it (in the meningeal spaces and choroid plexus) has been shown to be important for brain tissue maintenance and function. This review primarily explores recent findings concerning neuroimmune interactions and their mechanisms under homeostatic conditions. PMID- 27402498 TI - Antimony oxofluorides - a synthesis concept that yields phase pure samples and single crystals. AB - The single crystals of the new isostructural compounds Sb3O4F and Y0.5Sb2.5O4F and the two previously known compounds M-SbOF and alpha-Sb3O2F5 were successfully grown by a hydrothermal technique at 230 degrees C. The new compound Sb3O4F crystallizes in the monoclinic space group P21/c; a = 5.6107(5) A, b = 4.6847(5) A, c = 20.2256(18) A, beta = 94.145(8) degrees , z = 4. The replacing part of Sb with Y means a slight increase in the unit cell dimensions. The compounds M-SbOF and alpha-Sb3O2F5 have not been grown as single crystals before and it can be concluded that hydrothermal synthesis has proved to be a suitable technique for growing single crystals of antimony oxofluorides because of the relatively low solubility of such compounds compared to other antimony oxohalides that most often have been synthesised at high temperatures by solid state reactions or gas solid reactions. PMID- 27402494 TI - Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse. AB - Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders. PMID- 27402499 TI - A comparative proteomic study on the effects of metal pollution in oysters Crassostrea hongkongensis. AB - The metal pollution has posed great risk on the coastal organisms along the Jiulongjiang Estuary in South China. In this work, two-dimensional electrophoresis-based proteomics was applied to the oysters Crassostrea hongkongensis from metal pollution sites to characterize the proteomic responses to metal pollution. Metal accumulation and proteomic responses indicated that the oysters from BJ site were more severely contaminated than those from FG site. Compared with those oyster samples from the clean site (JZ), metal pollution induced cellular injuries, oxidative and immune stresses in oyster heapatopancreas from both BJ and FG sites via differential metabolic pathways. In addition, metal pollution in BJ site induced disturbance in energy and lipid metabolisms in oysters. Results indicated that cathepsin L and ferritin GF1 might be the biomarkers of As and Fe in oyster C. hongkongensis, respectively. This study demonstrates that proteomics is a useful tool for investigating biological effects induced by metal pollution. PMID- 27402495 TI - Role of Adiposity-Driven Inflammation in Depressive Morbidity. AB - Depression and metabolic disorders, including overweight and obesity, appear tightly interrelated. The prevalence of these conditions is concurrently growing worldwide, and both depression and overweight/obesity represent substantial risk factors for multiple medical complications. Moreover, there is now multiple evidence for a bidirectional relationship between depression and increased adiposity, with overweight/obesity being associated with an increased prevalence of depression, and in turn, depression augmenting the risk of weight gain and obesity. Although the reasons for this intricate link between depression and increased adiposity remain unclear, converging clinical and preclinical evidence points to a critical role for inflammatory processes and related alterations of brain functions. In support of this notion, increased adiposity leads to a chronic low-grade activation of inflammatory processes, which have been shown elsewhere to have a potent role in the pathophysiology of depression. It is therefore highly possible that adiposity-driven inflammation contributes to the development of depressive disorders and their growing prevalence worldwide. This review will present recent evidence in support of this hypothesis and will discuss the underlying mechanisms and potential therapeutic targets. Altogether, findings presented here should help to better understand the mechanisms linking adiposity to depression and facilitate the identification of new preventive and/or therapeutic strategies. PMID- 27402500 TI - The biodegradation of crude oil in the deep ocean. AB - Oil biodegradation at a simulated depth of 1500m was studied in a high-pressure apparatus at 5 degrees C, using natural seawater with its indigenous microbes, and 3ppm of an oil with dispersant added at a dispersant:oil ratio of 1:15. Biodegradation of the detectable hydrocarbons was prompt and extensive (>70% in 35days), although slower by about a third than under otherwise identical conditions equivalent to the surface. The apparent half-life of biodegradation of the total detectable hydrocarbons at 15MPa was 16days (compared to 13days at atmospheric pressure), although some compounds, such as the four-ring aromatic chrysene, were degraded rather more slowly. PMID- 27402501 TI - Anesthetist-Directed Sedation Favors Success of Advanced Endoscopic Procedures. AB - OBJECTIVES: Sedation is required to perform endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) given the duration and complexity of these advanced procedures. Sedation options include anesthetist-directed sedation (ADS) vs. gastroenterologist-directed sedation (GDS). Although ADS has been shown to shorten induction and recovery times, it is not established whether it impacts likelihood of procedure completion. Our aim was to assess whether ADS impacts the success of advanced endoscopy procedures. METHODS: We prospectively assessed the sedation strategy for patients undergoing ERCP and EUS between October 2010 and October 2013. Although assignment to ADS vs. GDS was not randomized, it was determined by day of the week. A sensitivity analysis using propensity score matching was used to model a randomized trial. The main outcome, procedure failure, was defined as an inability to satisfactorily complete the ERCP or EUS such that an additional endoscopic, radiographic, or surgical procedure was required. Failure was further categorized as failure due to inadequate sedation vs. technical problems. RESULTS: During the 3-year study period, 60% of the 1,171 procedures were carried out with GDS and 40% were carried out with ADS. Failed procedures occurred in 13.0% of GDS cases compared with 8.9% of ADS procedures (multivariate odds ratio (OR): 2.4 (95% confidence interval (CI): 1.5-3.6)).This was driven by a higher rate of sedation failures in the GDS group, 7.0%, than in the ADS group, 1.3% (multivariate OR: 7.8 (95% CI: 3.3-18.8)). There was no difference in technical success between the GDS and ADS groups (multivariate OR: 1.2 (95% CI: 0.7-1.9)). We were able to match 417 GDS cases to 417 ADS cases based on procedure type, indication, and propensity score. Analysis of the propensity score-matched patients confirmed our findings of increased sedation failure (multivariate OR: 8.9 (95% CI: 2.5-32.1)) but not technical failure (multivariate OR: 1.2 (0.7-2.2)) in GDS compared with ADS procedures. Adverse events of sedation were rare in both groups. Failed ERCP in the GDS group resulted in a total of 93 additional days of hospitalization. We estimate that $67,891 would have been saved if ADS had been used for all ERCP procedures. No statistically significant difference in EUS success was identified, although this sub-analysis was limited by sample size. CONCLUSION: ADS improves the success of advanced endoscopic procedures. Its routine use may increase the quality and efficiency of these services. PMID- 27402503 TI - Redox stability regulates community structure of active microbes at the sediment water interface. AB - Changes in redox conditions occur in a wide range of microbial habitats, in particular at the sediment-water interface (SWI) of aquatic systems. A mesocosm study using intact sediment cores from Lake Stechlin (Germany) was performed to investigate the impact of redox changes on microbial communities at the SWI. The SWI was exposed to permanent oxic (OX) or anoxic (ANOX) or to variable (VR) redox conditions, and for molecular analysis sediment samples were taken at the start and after seven days of the treatment. We performed 16S rRNA amplicon sequencing to identify redox-specific changes in the composition of metabolically active microbes. Generally, the community of active microbes in the VR cores was similar to in the OX cores, but differed significantly from the ANOX cores. Interestingly, VR conditions resulted in a high fraction of a Crenothrix-like microorganism increasing in read abundance from 4 to 5% initially, up to 69% over the experimental period. This implies that periodic redox fluctuations select for specific bacteria in environments such as seiches-affected sediments of stratified lakes. In Lake Stechlin sediment cores, these redox fluctuations lead to increased activities of specific microorganisms and high organic matter turnover rates with profound implications for aquatic organic matter cycling. PMID- 27402504 TI - Pathophysiological aspects of cystocele with a 3D finite elements model. AB - PURPOSES: The objective of this study is to design a 3D biomechanical model of the female pelvic system to assess pelvic organ suspension theories and understand cystocele mechanisms. METHODS: A finite elements (FE) model was constructed to calculate the impact of suspension structure geometry on cystocele. The sample was a geometric model of a control patient's pelvic organs. The method used geometric reconstruction, implemented by the biomechanical properties of each anatomic structure. Various geometric configurations were simulated on the FE method to analyse the role of each structure and compare the two main anatomic theories. RESULTS: The main outcome measure was a 3D biomechanical model of the female pelvic system. The various configurations of bladder displacement simulated mechanisms underlying medial, lateral and apical cystocele. FE simulation revealed that pubocervical fascia is the most influential structure in the onset of median cystocele (essentially after 40 % impairment). Lateral cystocele showed a stronger influence of arcus tendineus fasciae pelvis (ATFP) on vaginal wall displacement under short ATFP lengthening. In apical cystocele, the uterosacral ligament showed greater influence than the cardinal ligament. Suspension system elongation increased displacement by 25 % in each type of cystocele. CONCLUSIONS: A 3D digital model enabled simulations of anatomic structures underlying cystocele to better understand cystocele pathophysiology. The model could be used to predict cystocele surgery results and personalising technique by preoperative simulation. PMID- 27402502 TI - Comparison of Efficacy of Prophylactic Endoscopic Therapies for Postpolypectomy Bleeding in the Colorectum: A Systematic Review and Network Meta-Analysis. AB - OBJECTIVES: Although various endoscopic therapies have been suggested for preventing bleeding after colorectal polypectomy, the optimal therapy has yet to be fully clarified. We assessed the comparative efficacy of prophylactic therapies for postpolypectomy bleeding through a network meta-analysis combining direct and indirect comparisons. METHODS: We searched for all relevant randomized controlled trials published up until January 2016 examining the effects of prophylactic therapy for bleeding after colorectal polypectomy. The types of prophylactic therapy were classified as mechanical therapy, epinephrine-saline injection therapy, coagulation therapy, combined therapy, or no prophylactic therapy. Combined therapy was defined as a combination of two or more types of therapy including mechanical therapy, epinephrine-saline injection therapy, and coagulation therapy. We performed a Bayesian network meta-analysis for all prophylactic therapies. RESULTS: Fifteen studies with 3,462 patients were included in the meta-analysis. Compared with no prophylactic therapy, both epinephrine-saline injection and mechanical therapy showed superiority for preventing early postpolypectomy bleeding with a moderate quality of evidence (injection therapy, risk ratio (RR; 95% credible interval (CrI))=0.32 (0.11 0.67); mechanical therapy, RR (95% CrI)=0.13 (0.03-0.37)). Combined therapy did not show a statistically significant difference for decreasing the risk of early bleeding compared with injection or mechanical therapies, respectively (combined vs. injection therapy: RR (95% CrI)=0.35 (0.10-1.00); combined vs. mechanical therapy: RR (95% CrI)=0.88 (0.23-3.00)). In cases of delayed bleeding, no type of prophylactic therapy decreased the risk of bleeding compared with no prophylactic therapy. CONCLUSIONS: Either mechanical therapy or injection therapy reduced the risk of early postpolypectomy bleeding. As for delayed bleeding, none of the prophylactic therapies was associated with a lower risk of bleeding compared with no prophylactic therapy. PMID- 27402505 TI - Cardiovascular disease incidence among females in South Carolina by type of oral contraceptives, 2000-2013: a retrospective cohort study. AB - INTRODUCTION: Certain types of oral contraceptives can produce favorable effects on lipid metabolism and vascular tone, while others have potentially detrimental effects. Endogenous and exogenous hormones exert different effects on high density lipoprotein (HDL) and low-density lipoprotein (LDL) depending on the type, combination, and dose of the hormone. The estrogenic and progestogenic effects of exogenous hormones on HDL and LDL are inconsistent. Studying surrogate end points (LDL, HDL levels) may provide a misleading picture of OCs. METHODS: Medicaid data from 2000 to 2013 were used to assess the relationship between the type of OCs and CVD incidence. Multivariable logistic regression was used to model relationships between cardiovascular disease and OC use adjusting for potential confounders. RESULTS: Compared to combined oral contraceptives (COC), progestin-only oral contraceptives (POC) were associated with decreased heart disease and stroke incidence after adjusting for important covariates (OR 0.74; 95 % CI 0.57, 0.97 and OR 0.39; 95 % CI 0.16, 0.95, respectively). However, there was a positive association between POC + COC and both heart disease and stroke incidence (OR 2.28; 95 % CI 1.92, 2.70 and OR 2.12; 95 % CI 1.34, 3.35, respectively). CONCLUSION: In light of an association between POC use and decreased heart disease and stroke, women's CVD risk factors should be carefully considered when choosing which OC to use. Baseline CVD risk should be a part of the discussion between women and their primary care providers when making choices regarding OCs. PMID- 27402506 TI - Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma. AB - PURPOSE: Metformin is the most prescribed anti-diabetic medication worldwide because of its proven efficacy and limited side effects. In this study, the significant anticancer effect of metformin was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells. METHODS: We tested the growth inhibition assay using MTT cell proliferation, cell cycle assay, apoptosis assessment with flow cytometry using propidium iodide and Annexin V, and autophagy protein expression with western blot analysis. RESULTS: Metformin inhibited the growth of cancer cells with different concentrations in a dose- and time-dependent manner. Moreover, the inhibition properties observed as a function of increased concentrations of metformin were markedly augmented when the medication was administered in the progesterone-resistant Ishikawa cells, even with a dose as low as 10 mM. The early and late phases of apoptosis were enhanced in the metformin-treated tumour cells that were analyzed. For the Ishikawa cells, the expression of p-AMPK, LC-3, and beclin1 was upregulated after treatment, whereas the AMPK levels were not modulated. Furthermore, for the Ishikawa-PR cells, the protein levels were similarly upregulated. Finally, we observed that the three proteins showed much more variability in Ishikawa-PR cells than in Ishikawa cells. CONCLUSION: The application of metformin to target autophagy in endometrial cancer cells provides a new potential treatment for progesterone-resistant endometrial carcinoma. PMID- 27402507 TI - Fusarium musae, a not so uncommon human pathogen - bananas suffering from Fusarium musae post-harvest disease as most likely source of human infection. PMID- 27402508 TI - A case of Cryptococcus neoformans meningitis in a patient with abnormal levels of isolated immunological markers. AB - Cryptococcal meningitis is considered rare in immunocompetent patients and is mainly a disease of immunocompromised patients. We report a case of cryptococcal meningitis, due to Cryptococcus neoformans, in an apparently healthy individual with abnormal levels of isolated immunological markers. Regardless of the patient's immune status, the result of the disease can be serious unless the disease is diagnosed early. PMID- 27402509 TI - Highlights of DNA Barcoding in identification of salient microorganisms like fungi. AB - Fungi, the second largest kingdom of eukaryotic life, are diverse and widespread. Fungi play a distinctive role in the production of different products on industrial scale, like fungal enzymes, antibiotics, fermented foods, etc., to give storage stability and improved health to meet major global challenges. To utilize algae perfectly for human needs, and to pave the way for getting a healthy relationship with fungi, it is important to identify them in a quick and robust manner with molecular-based identification system. So, there is a technique that aims to provide a well-organized method for species level identifications and to contribute powerfully to taxonomic and biodiversity research is DNA Barcoding. DNA Barcoding is generally achieved by the retrieval of a short DNA sequence - the 'barcode' - from a standard part of the genome and that barcode is then compared with a library of reference barcode sequences derived from individuals of known identity for identification. PMID- 27402510 TI - Chiengi District, Zambia Open Defecation Free After 1 Year of Community-Led Total Sanitation. AB - Nearly one quarter of Zambians lack access to sanitation facilities. In rural communities, the government of Zambia adopted community-led total sanitation (CLTS) to address this problem. One year after the implementation of a mobile-to web monitored CLTS intervention, Chiengi District, Zambia, was verified as open defecation free with complete 100% coverage of household-level latrines. Chiefs and traditional leaders led the achievement. Impacts on individual health are yet to be measured in a robust way. PMID- 27402512 TI - Cholera and ABO Blood Group: Understanding an Ancient Association. PMID- 27402511 TI - National Malaria Prevalence in Cambodia: Microscopy Versus Polymerase Chain Reaction Estimates. AB - Accurate information regarding malaria prevalence at national level is required to design and assess malaria control/elimination efforts. Although many comparisons of microscopy and polymerase chain reaction (PCR)-based methods have been conducted, there is little published literature covering such comparisons in southeast Asia especially at the national level. Both microscopic examination and PCR detection were performed on blood films and dried blood spots samples collected from 8,067 individuals enrolled in a nationwide, stratified, multistage, cluster sampling malaria prevalence survey conducted in Cambodia in 2007. The overall malaria prevalence and prevalence rates of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae infections estimated by microscopy (N = 8,067) were 2.74% (95% confidence interval [CI]: 2.39-3.12%), 1.81% (95% CI: 1.53-2.13%), 1.14% (95% CI: 0.92-1.40%), and 0.01% (95% CI: 0.003 0.07%), respectively. The overall malaria prevalence based on PCR detection (N = 7,718) was almost 2.5-fold higher (6.31%, 95% CI: 5.76-6.89%, P < 0.00001). This difference was significantly more pronounced for P. falciparum (4.40%, 95% CI: 3.95-4.90%, P < 0.00001) compared with P. vivax (1.89%, 95% CI: 1.60-2.22%, P < 0.001) and P. malariae infections (0.22%, 95% CI: 0.13-0.35%, P < 0.0001). The significant proportion of microscopy-negative but PCR-positive individuals (289/7,491, 3.85%) suggest microscopic examination frequently underestimated malaria infections and that active case detection based on microscopy may miss a significant reservoir of infection, especially in low-transmission settings. PMID- 27402514 TI - Bullous Scabies. AB - Scabies is a common contagious cutaneous disease and usually affects the young, characterized by polymorphous lesions that may present as burrows, pruritic papules, and inflammatory nodules. Bullous scabies (BS) is its rather rare subtype, mimicking bullous pemphigoid. We report a 15-year-old Chinese boy presenting with 1-month history of pruritic bullae on his penile skin, showing poor response to both topical steroids and systemic antihistamines, but cured by sulfur ointment alone. No recurrence occurred in the 5 years of follow-up. We also reviewed the published cases. Up to date, 44 cases, including the present, have been reported. Of them, 30 were male and 14 were female. The age range was from 1 to 89 years old, with a median age of 70.6 years. The bullous lesions may involve the arms, legs, trunk, genitals, feet, buttocks, thighs, neck, inguinal folds, and may even be generalized. Trunk and extremities are the most common involved locations. Facial or mucosa involvement had never been reported. The histological findings present as a subepidermal split with variable inflammatory infiltrate predominantly neutrophils, and eosinophilic spongiosis, or both. Eighteen of 32 patients showed positive deposition of linear-granular IgG or complement 3 alone or in various combinations, and five of 24 patients revealed circulating IgG. All the 40 cases with therapeutic details were cured by antiscabietic remedy. BS always involves the trunk and extremities. It has a predilection for elderlies and males. The treatments for BS are similar to those of classical scabies. PMID- 27402515 TI - What Do We Know About Chagas Disease in the United States? AB - Chagas disease, caused by the parasite Trypanosoma cruzi, affects more than 5 million people worldwide leading to serious heart and gastrointestinal disease in a proportion of chronically infected patients. Important modes of transmission include vector-borne, congenital, and via blood transfusion or organ transplant from an infected donor. Vector-borne transmission of Chagas disease occurs in the Americas, including the southern half of North America, where the specific vector insects (triatomines), T. cruzi, and infected reservoir mammalian hosts are found. In the United States, there are estimated to be at least 300,000 cases of chronic Chagas disease among people originally from countries of Latin America where Chagas disease is endemic. Fewer than 30 cases of locally acquired infection have been documented in the United States, although a sylvatic transmission cycle has been known to exist in this country for at least a century. Studies defining risks for locally acquired infection and effective prevention strategies are needed to help prevent domestic transmission of T. cruzi To help address Chagas disease in the United States, improved health-care provider awareness and knowledge, better tools for screening and diagnosing patients, and wider availability of treatment drugs are needed. PMID- 27402513 TI - Global Epidemiology of Plasmodium vivax. AB - Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded. PMID- 27402516 TI - Deployable Molecular Detection of Arboviruses in the Australian Outback. AB - The most common causes of human infection from the arboviruses that are endemic in Australia are the arthritogenic alphaviruses: Ross River virus (RRV) and Barmah Forest virus (BFV). The most serious infections are caused by the neurotropic flaviviruses, Murray Valley encephalitis virus (MVEV) and the Kunjin subtype of West Nile virus. The greatest individual risk of arbovirus infection occurs in tropical/subtropical northern Australia because of the warm, wet summer conditions from December to June, where conventional arbovirus surveillance is difficult due to a combination of low population density, large distances between population centers, poor roads, and seasonal flooding. Furthermore, virus detection requires samples to be sent to Perth up to 2,000 km away for definitive analysis, causing delays of days to weeks before test results are available and public health interventions can be started. We deployed a portable molecular biology laboratory for remote field detection of endemic arboviruses in northern Queensland, then in tropical Western Australia and detected BFV, MVEV, and RRV RNA by polymerase chain reaction (PCR) assays of extracts from mosquitoes trapped in Queensland. We then used a field-portable compact real-time thermocycler for the samples collected in the Kimberley region of Western Australia. Real-time field PCR assays enabled concurrent endemic arbovirus distribution mapping in outback Queensland and Western Australia. Our deployable laboratory method provides a concept of operations for future remote area arbovirus surveillance. PMID- 27402517 TI - Atypical Mansonella ozzardi Microfilariae from an Endemic Area of Brazilian Amazonia. AB - Mansonellosis is endemic in several regions of Africa, the Caribbean, and Latin America. Mansonella ozzardi and Mansonella perstans have been reported in Latin America, including the Amazon region. A morphological and molecular microfilariae study was performed in Pauini (Brazil). Blood samples were collected from 40 individuals, and were analyzed by Giemsa-stained blood film and by two different nested polymerase chain reactions which detect internal transcribed spacer-1 and the major sperm protein gene. By microscopy, 14 of 40 were positive: 11 as M. ozzardi and three as M. perstans-like infections. Both molecular methods detected 19 positive cases as M. ozzardi, including those 14 individuals detected by microscopy, without detectable genetic differences among any of the 19 positive samples. Molecular techniques showed an improvement of mansonellosis diagnosis and may become an effective tool to evaluate the present status of M. ozzardi and M. perstans in Latin America. PMID- 27402518 TI - Zika Virus and Chikungunya Virus CoInfections: A Series of Three Cases from a Single Center in Ecuador. AB - Zika virus (ZIKV) and chikungunya virus (CHIKV) cocirculate throughout much of the tropical Western Hemisphere; however, few cases of coinfection with these two pathogens have been reported. Herein, we describe three cases of ZIKV-CHIKV coinfection detected at a single center in Ecuador: a patient who developed symptoms on postoperative day 5 from an orthopedic procedure, a woman who had traveled to Ecuador for fertility treatment, and a woman who was admitted for Guillain-Barre syndrome and had ZIKV and CHIKV detected in serum and cerebrospinal fluid. All cases were diagnosed using a multiplex real-time reverse transcription polymerase chain reaction, and ZIKV viremia was detected as late as 16 days after symptom onset. These cases demonstrate the varied clinical presentation of ZIKV-CHIKV coinfections as well as the importance of multiplexed arboviral testing for these pathogens. PMID- 27402520 TI - Thoracic Myelopathy Due to Gnathostomiasis Acquired in New Zealand. AB - Gnathostomiasis is a zoonotic disease endemic in Asia. It most commonly manifests as gastrointestinal and cutaneous disease. Central nervous system involvement is a rare but feared complication, often leaving patients with permanent neurologic deficits. Clinicians outside of Asia and Latin America may have little experience with this illness, causing delays in diagnosis and treatment. We describe a 40 year-old woman who developed a progressive myelopathy over 18 months. She had never traveled outside of New Zealand. Cerebrospinal fluid (CSF) showed marked eosinophilia and Gnathostoma serology was positive in both serum and CSF. This is the first report of gnathostomiasis acquired in New Zealand, and the first case of neurognathostomiasis reported outside Asia. Clinicians should include neurognathostomiasis in the differential diagnosis of myelopathy and CSF eosinophilia, even if there is no history of travel to endemic areas. PMID- 27402519 TI - Spotted Fever Group Rickettsioses and Murine Typhus in a Malaysian Teaching Hospital. AB - Limited information is available on the etiological agents of rickettsioses in southeast Asia. Herein, we report the molecular investigation of rickettsioses in four patients attending a teaching hospital in Malaysia. DNA of Rickettsia sp. RF2125, Rickettsia typhi, and a rickettsia closely related to Rickettsia raoultii was detected in the blood samples of the patients. Spotted fever group rickettsioses and murine typhus should be considered in the diagnosis of patients with nonspecific febrile illness in this region. PMID- 27402521 TI - Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka. AB - A gap in the leptospirosis field remains the lack of well-characterized sample collections that allow for comparison of new methods to standard ones. In the context of a flood-related outbreak of leptospirosis evaluated in Anuradhapura, Sri Lanka, a specimen bank was obtained with detailed metadata accompanied by gold standard diagnostic test results. Blood samples collected on admission and 14 days later from suspected cases of leptospirosis were tested using microscopic agglutination test (MAT) (17 serovars), an in-house enzyme-linked immunosorbent assay (ELISA) using a locally obtained strain of Leptospira kirschneri as sonicated antigen, a commercially available ELISA based on sonicated Leptospira biflexa, and a quantitative polymerase chain reaction (qPCR) assay targeting the pathogenic Leptospira-specific 16S rRNA gene. Of 62 patients presenting within the first 2 days of illness, 31 had confirmed leptospirosis based either on paired-sample MAT or qPCR. During the acute phase, qPCR was most sensitive, detecting 74% of definitively diagnosed cases; immunoglobulin G (IgG) ELISA (in house), IgG ELISA (commercial), and MAT had sensitivities of 35.5%, 12.0%, and 22.6%, respectively, in detecting definitively diagnosed cases using acute phase serum. Of 40 patients with paired sera, 10 were qPCR positive. Of these, five samples were negative by paired-sample MAT. Of the 11 MAT-positive samples, only five were detected using qPCR confirming that both tests are needed for maximal sensitivity. Regional leptospiral serovar-specific IgG ELISA was superior to MAT. Knowing the regionally dominant serovars improves serological sensitivity in the analysis of acute specimens by ELISA, but qPCR was most sensitive in this patient population. PMID- 27402522 TI - Two Cases of Leprosy in Siblings Caused by Mycobacterium lepromatosis and Review of the Literature. AB - We describe two leprosy cases in Mexican siblings caused by a new species Mycobacterium lepromatosis This is likely the first report of family clustering of this infection. The patients showed severe prolonged leprosy reactions after antimicrobial treatment, raising a challenge for clinical management. The current status of M. lepromatosis infection is reviewed. PMID- 27402523 TI - The First Reported Outbreak of Chikungunya in the U.S. Virgin Islands, 2014-2015. AB - The chikungunya virus (CHIKV) epidemic in the Americas is of significant public health importance due to the lack of effective control and prevention strategies, severe disease morbidity among susceptible populations, and potential for persistent arthralgia and long-term impaired physical functionality. Using surveillance data of suspected CHIKV cases, we describe the first reported outbreak in the U.S. Virgin Islands. CHIKV incidence was highest among individuals aged 55-64 years (13.1 cases per 1,000 population) and lowest among individuals aged 0-14 years (1.8 cases per 1,000 population). Incidence was higher among women compared to men (6.6 and 5.0 cases per 1,000 population, respectively). More than half of reported laboratory-positive cases experienced fever lasting 2-7 days, chills/rigor, myalgia, anorexia, and headache. No clinical symptoms apart from the suspected case definition of fever >= 38 degrees C and arthralgia were significantly associated with being a reported laboratory positive case. These results contribute to our knowledge of demographic risk factors and clinical manifestations of CHIKV disease and may aid in mitigating future CHIKV outbreaks in the Caribbean. PMID- 27402524 TI - Hepatitis B Virus Infection in Indonesia 15 Years After Adoption of a Universal Infant Vaccination Program: Possible Impacts of Low Birth Dose Coverage and a Vaccine-Escape Mutant. AB - A universal hepatitis B vaccination program for infants was adopted in Indonesia in 1997. Before its implementation, the prevalence of hepatitis B surface antigen (HBsAg)-positive individuals in the general population was approximately 5-10%. The study aimed to investigate the hepatitis B virus (HBV) serological status and molecular profile among children, 15 years after adoption of a universal infant vaccination program in Indonesia. According to the Local Health Office data in five areas, the percentages of children receiving three doses of hepatitis B vaccine are high (73.9-94.1%), whereas the birth dose coverage is less than 50%. Among 967 children in those areas, the seropositive rate of HBsAg in preschool- and school-aged children ranged from 2.1% to 4.2% and 0% to 5.9%, respectively. Of the 61 HBV DNA-positive samples, the predominant genotype/subtype was B/adw2 Subtype adw3 was identified in genotype C for the first time in this population. Six samples (11.5%) had an amino acid substitution within the a determinant of the S gene region, and one sample had T140I that was suggested as a vaccine escape mutant type. The low birth dose coverage and the presence of a vaccine escape mutant might contribute to the endemicity of HBV infection among children in Indonesia. PMID- 27402525 TI - Concurrent nonindependent fixed-ratio schedules of alcohol self-administration: Effects of schedule size on choice. AB - Choice behavior was studied under concurrent nonindependent fixed-ratio fixed ratio (nFR) schedules of reinforcement, as these schedules result in frequent changeover responses. With these schedules, responses on either operandum count toward the completion of the ratio requirements of both schedules. Five monkeys were subjects, and two pairs of liquid reinforcers were concurrently available: 16% (w/v) and 0% ethanol or 16% and 8% ethanol. For each pair of reinforcers, the nFR sizes were systematically altered across sessions while keeping the schedule size equal for both liquids. Responding varied as a function of reinforcer pair and nFR size. With the 16% and 0% pair, higher response rates were maintained by 16% and were an inverted U-shape function of nFR size. With 16% and 8%, a greater number of responses initially occurred on the schedule that delivered 8% ethanol. However, as nFR size increased, preference reversed such that responses that delivered 16% ethanol were greater. When the nFR size was subsequently decreased, preference reverted back to 8%. Number of responses emitted per delivery was a dependent variable and, in behavioral economic terms, was the price paid for each liquid delivery. With 16% and 0%, changeover responses initially increased and then decreased as schedule size became larger. In contrast, with the 16% and 8% pair, changeover responses increased directly with schedule size. Responding under nFR schedules is sensitive to differences in reinforcer magnitude and demonstrates that relative reinforcing effects can change as a function of schedule size. PMID- 27402527 TI - An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin. AB - PURPOSE: To compare in vitro properties of 4 drug-eluting embolic agents loaded with doxorubicin. MATERIALS AND METHODS: DC Bead (100-300 um), LifePearl (200 um), HepaSphere (30-60 um), and Tandem (100 um) microspheres were loaded with 40 mg/20 mL of doxorubicin per milliliter of microspheres. Loading, elution, diameter changes after loading, changes in the amount of doxorubicin loaded over 2 weeks in storage, and time in suspension were evaluated. RESULTS: All microspheres loaded > 99% doxorubicin within 1 hour. In vitro elution reached a plateau by 6 hours, with 30% +/- 5, 21% +/- 2, 8% +/- 3, and 6% +/- 0 of the loaded doxorubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem microspheres, respectively, with at least 1 statistically significant difference between at least 2 of the products in doxorubicin eluted at every time point. The times to elute 75% of the total released doxorubicin were 197, 139, 110, and 77 min for DC Bead, LifePearl, HepaSphere, and Tandem microspheres, respectively. The average diameters of LifePearl, DC Bead, and Tandem microspheres were reduced after loading by 24%, 20%, and 9%, respectively. After suspension in contrast medium, no changes were observed in doxorubicin loading over 2 wk. After loading, times in suspension were 8.4 min +/- 0.2, 6.0 min +/- 0.1, 3.1 min +/- 0.2, and 2.9 min +/- 0.3 for Tandem, LifePearl, DC Bead, and HepaSphere microspheres, respectively. CONCLUSIONS: Although drug-eluting embolic agents universally loaded doxorubicin within 1 hour, the elution amounts, rates of release, diameter shrinkage, and times in suspension varied by product. PMID- 27402526 TI - Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Prediction of Early Arterial Blood Flow Stasis in Radioembolization of Breast Cancer Liver Metastases. AB - PURPOSE: To retrospectively evaluate predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for early arterial blood flow stasis during transarterial radioembolization (TARE) of liver dominant breast metastases (LdBM). MATERIALS AND METHODS: Preinterventional 1.5T DWI (b0, b1, b2 = 0, 50, 800 s/mm(2)) data for 28 liver lobes of 18 female patients treated by resin-based radioembolization (10 bilobar and 8 unilobar treatments) were analyzed. Apparent diffusion coefficient (ADC) (0, 800) and an estimation of the true diffusion coefficient D' and of the perfusion fraction f' were calculated for the 2 largest metastases. Response rate at 3 months and survival were analyzed. Procedures without full dose application because of early stasis were assigned to group A (n = 15), and procedures with full dose application were assigned to group B (n = 13). RESULTS: Metastases in group A showed significantly lower f' (0.035 +/- 0.018 vs 0.076 +/- 0.015, P < .0001) and a trend toward lower ADC(0, 800) with values given in 10(-6) mm(2)/s (1,066 +/- 141 vs 1,189 +/- 176, P = .051); no group difference was shown for D'. Groups were best discriminated by weighted mean f' values of the 2 largest metastases with accuracy of 100%. Mean tumor diameter before and after TARE was 51 mm +/- 18 and 50 mm +/- 24 in group A and 47 mm +/- 27 and 48 mm +/- 32 for group B. Imaging response did not differ between groups (P = .545). Overall survival did not differ significantly between group A (230 d) and B (155 d) (P = .124). CONCLUSIONS: Perfusion sensitive IVIM parameter f' may predict early blood flow stasis in patients undergoing TARE for LdBM. Determination of this parameter before intervention may increase awareness of the interventionalist and increase safety of microsphere administration. PMID- 27402528 TI - Comparison of Early Sac Shrinkage with Third-Generation Stent Grafts for Endovascular Aneurysm Repair. AB - PURPOSE: To compare the effects of the currently most-used third-generation stent grafts on early aneurysm sac shrinkage, a proposed marker of successful endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: EVARs performed from 2009 to 2013 at 2 institutions were retrospectively analyzed. Patients treated with a Zenith, EXCLUDER, or Endurant device who completed imaging studies before EVAR and at 1, 6, 12, and 24 months afterward were included. Sac shrinkage was compared by volumetry. RESULTS: Among 296 EVAR procedures, 47 were excluded for the use of different stent grafts and 87 for loss to follow-up or missing required imaging study, leaving 162 EVAR procedures (69 Zenith, 54 EXCLUDER, and 39 Endurant devices) for analysis. Mixed-effects model analysis revealed that the use of a Zenith device resulted in significantly greater shrinkage compared with EXCLUDER and Endurant devices (both P < .001). The differences were statistically significant from 1 month after EVAR (average sac shrinkage at 1 mo for Zenith, EXCLUDER, and Endurant devices of 95.3%, 100.3%, and 102.6%, respectively), indicating an early shrinkage advantage for Zenith devices. In addition, multivariate analysis revealed Zenith device use to be a sole beneficial factor for sac shrinkage at 24 months after EVAR (odds ratio, 2.881; 95% confidence interval, 1.331-6.235; P = .007). Repeat intervention rates (all for treatment of type II endoleaks) for Zenith, EXCLUDER, and Endurant devices were 2.9% (2 of 69), 1.9% (1 of 54), and 2.6% (1 of 39), respectively. CONCLUSIONS: Zenith device use was associated with significantly better early sac shrinkage. In view of the limited follow-up period, whether these differences lead to improved clinical outcomes remains unclear. PMID- 27402529 TI - Hydrogen peroxide-induced oxidative damage in peripheral blood lymphocytes from rats chronically treated with corticosterone: The protective effect of oxytocin treatment. AB - Contemporary lifestyle is commonly associated with chronic stress, an environmental factor contributing to development of various psychological and somatic disorders. Increased levels of glucocorticoids, observed in the chronic stress, induce the production of reactive oxygen species leading to genotoxicity. The aim of this study was to investigate whether chronic administration of oxytocin (OXY) 10 IU/400 MUL/day, s.c., for 14 days, a hormone presumed to exert antioxidant effect, may prevent DNA damage in the comet assay of peripheral blood lymphocytes of Wistar rats treated chronically with corticosterone (CORT) 100 mg/L ad libitum, per os, for 21 days, as well as, to influence some plasma oxidative stress parameters, i.e. levels of total lipid hydroperoxide (LOOH), and malondialdehyde (MDA), and the activity of antioxidative enzyme superoxide dismutase (SOD). Even though there was no reduction in overall number of damaged cells after oxytocin treatment only, the marked increase in total comet score (TCS) after incubation with H2O2 in CORT group compared to controls, was absent in the CORT + OXY experimental group. Furthermore, significant decrease of highly damaged cells compared to corticosterone group was noted. Chronic oxytocin administration thus protected lymphocytes from high intensity damage that leads to cellular death. In addition, treatment with OXY along with CORT, significantly decreased concentration of LOOH in plasma, and increased SOD compared to CORT treatment only. This finding corresponds well with current reports on beneficial effects of OXY in conditions of HPA axis hyperactivity, and supports the hypothesis of OXY-mediated antioxidant action. PMID- 27402531 TI - Neighboring pi-Amide Participation in Thioether Oxidation: Conformational Control. AB - The electrochemical oxidation of thioethers is shown to be facilitated by neighboring amide participation. (1)H NMR spectroscopic analysis in acetonitrile solution of two conformationally constrained compounds with such facilitation shows that two-electron participation by the amide pi2 orbital can occur to stabilize the developing sulfur radical cation. PMID- 27402530 TI - Experiences of prenatal diagnosis and decision-making about termination of pregnancy: A qualitative study. AB - BACKGROUND: Advances in genetic technologies and ultrasound screening techniques have increased the ability to predict and diagnose congenital anomalies during pregnancy. As a result more prospective parents than ever before will receive a prenatal diagnosis of a fetal abnormality. Little is known about how Australian women and men experience receiving a prenatal diagnosis and how they make their decision about whether or not to continue the pregnancy. AIMS: This qualitative study aims to describe parental experiences and examine how best to provide support after a prenatal diagnosis. RESULTS: Individual in-depth interviews were conducted with 102 women and men approximately six weeks post-diagnosis of fetal abnormality. Data were elicited using a narrative, chronological approach and women (n = 75) and a sample of male partners (n = 27) were separately interviewed. Thematic analysis, involving a rigorous process of qualitative coding, enabled iterative development and validation of emergent themes. Participants identified that the shock of the diagnosis can be lessened when good care is delivered, by provision of: clear, accurate and respectful communication; empathic, non-judgemental, professional support; timely access to further testing and appointments; seamless interactions with services and administration; appropriate choices about invasive testing; acknowledgment of the enormity and unexpected nature of the diagnosis, and of the subsequent decision-making challenges; and discussion of the myriad feelings likely to emerge throughout the process. CONCLUSIONS: This study has demonstrated the importance of providing timely access to accurate information and supportive, non-judgemental care for women and their partners following prenatal diagnosis of a fetal abnormality. PMID- 27402532 TI - Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength. AB - Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the beta-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is proposed to explain how BMPR1A controls bone remodeling by inhibiting cell proliferation and stimulating differentiation. It is reported that RANKL and SOST are abundantly expressed by osteocytes. Thus, BMP signaling through BMPR1A plays important roles in osteocytes. PMID- 27402534 TI - STED imaging of tau filaments in Alzheimer's disease cortical grey matter. AB - Alzheimer's disease (AD) involves the propagation of filaments of tau protein throughout the cerebral cortex. Imaging tau filaments and oligomers in human brain at high resolution would help contribute insight into the mechanism and progression of tauopathic diseases. STED microscopy is a nano-scale imaging technique and we aimed to test the abilities of this method for resolving tau structures within human brain. Using autopsied 50MUm AD brain sections, we demonstrate that STED microscopy can resolve immunolabelled tau filaments at 77nm resolution. Ribbon-like tau filaments imaged by STED appeared smooth along their axis with limited axial undulations. STED also resolved 70-80nm wide tau puncta. Of the fluorophores tested, STAR635p was optimal for STED imaging in this tissue. This was in part due to brain tissue autofluorescence within the lower wavelength ranges (488-590nm). Further, the stability and minimal photobleaching of STAR635p allowed STED z-stacks of neurons packed with tau filaments (neurofibrillary tangles) to be collated. There was no loss of x-y image resolution of individual tau filaments through the 20MUm z-stack. This demonstrates that STED can contribute to nano-scale analysis and characterisation of pathologies within banked human autopsied brain tissue. Resolving tau structures at this level of resolution provides promising avenues for understanding mechanisms of pathology propagation in the different tauopathies as well as illuminating what contributes to disease heterogeneity. PMID- 27402533 TI - Crystal structure of DPF3b in complex with an acetylated histone peptide. AB - Histone acetylation plays an important role in chromatin dynamics and is associated with active gene transcription. This modification is written by acetyltransferases, erased by histone deacetylases and read out by bromodomain containing proteins, and others such as tandem PHD fingers of DPF3b. Here we report the high resolution crystal structure of the tandem PHD fingers of DPF3b in complex with an H3K14ac peptide. In the complex structure, the histone peptide adopts an alpha-helical conformation, unlike previously observed by NMR, but similar to a previously reported MOZ-H3K14ac complex structure. Our crystal structure adds to existing evidence that points to the alpha-helix as a natural conformation of histone tails as they interact with histone-associated proteins. PMID- 27402535 TI - Crystal structure of the Trim5alpha Bbox2 domain from rhesus macaques describes a plastic oligomerisation interface. AB - Retroviral pathogens have been an evolutionary pressure for many primate species, driving the development of an intrinsic cellular response to retroviruses and antiretroviral proteins. One such antiretroviral protein is the restriction factor Trim5alpha, that blocks HIV-1 infection in rhesus macaques at an early post-entry stage in the retroviral lifecycle. Trim5alpha self-assembles into a large hexagonal array, complimentary to the retroviral capsid. Assembly is mediated by the conserved N-terminal architecture comprising a RING domain, a Bbox domain, and a coiled coil. Recently we have shown that the Bbox domain and elements of the coiled coil form a trimer in solution, and that the Bbox domain drives assembly. During crystallisation experiments using the trimer forming construct, we determined the structure of a dimeric Bbox domain to a resolution of 1.8A. Interface analysis reveals that residues previously shown to be required for assembly and restriction, Glu120 and Arg121, are central to the interface. Comparison to a mutant Trim5alpha dimer interface shows a translation of the Bbox dimerisation interface removing interactions important in the wildtype protein. PMID- 27402536 TI - Human TTR conformation altered by rhenium tris-carbonyl derivatives. AB - Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu(82), may represent a form of TTR better at scavenging beta-Amyloid. At a resolution of 1.69A, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non isomorphism. PMID- 27402537 TI - Aging of hematopoietic stem cells: DNA damage and mutations? AB - Aging in the hematopoietic system and the stem cell niche contributes to aging associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly larger amount of gammaH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared with young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase in and nature of DNA mutations in the hematopoietic system with age, the quality of the DNA damage response in aged HSCs, and the nature of gammaH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or three-dimensional architecture of the cell as major cell intrinsic factors of HSCs aging. Aging of HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSC aging in the light of these novel mechanisms of aging of HSCs. PMID- 27402538 TI - Origin of the stem cell niche concept. PMID- 27402539 TI - Johnson & Johnson is ordered to pay $70m to boy who developed gynecomastia. PMID- 27402540 TI - Invasive sinonasal adenocarcinoma with an absent olfactory bulb: a case report. AB - Sinonasal adenocarcinomas are rare, locally invasive tumours. In this case the symptomatic profile was unusual and the diagnosis was missed at the primary care stage. Interestingly this would be the first documented case with an absent ipsilateral olfactory bulb. A 55-year old male presented with symptoms of behavioural change and mild headaches. He was later found to have a large Sinonasal adenocarcinoma which penetrated the skull base. This was treated by a combined craniotomy and endonasal approach. Sinonasal adenocarcinomas are unusual tumours and further research is required in order to clarify management strategies and prognosis. This interesting case was more unusual again given its presentation, extent and absence of the olfactory bulb. Importantly for primary care physicians the initial diagnosis was considered psychiatric rather than organic; despite there being specific features of the presentation which were suggestive of an intra-cranial lesion. PMID- 27402541 TI - Necrotizing fasciitis of anterior abdominal wall following cesarean section in a low-risk patient. AB - We report a case of a mono-microbial post-cesarean necrotizing fasciitis caused by methicillin resistant Staphylococcus aureus, in a low-risk healthy woman who presented with acute fulminant infection, sepsis and features of multi-organ dysfunction syndrome on sixth post-operative day. Aggressive management with multiple surgical debridement and supportive therapy was the key to favorable outcome in this case. PMID- 27402542 TI - A case of postoperative recurrent cholangitis after pancreaticoduodenectomy successfully treated by tract conversion surgery. AB - A 69-year-old man, who had undergone pylorus-preserving pancreaticoduodenectomy (PD) (Imanaga procedure) for duodenum papilla cancer 13 years prior, had a history of repeated hospitalization due to cholangitis since the third year after surgery and liver abscess at the 10th year after surgery. Gastrointestinal series indicated no stenosis after the cholangiojejunostomy. However, reflux of contrast media into the bile duct and persistence of food residues were observed. We considered the cholangitis to be caused by reflux and persistence of food residues into the bile duct. So, we performed the tract conversion surgery, Imanaga procedure to Child method. The postoperative course was good even after re-initiating dietary intake. He was discharged on the 19th day after surgery. He has not experienced recurrent cholangitis for 18 months. For patients with post PD recurrent cholangitis caused by reflux of food residues like ours, surgical treatment should be considered because tract conversion may be an effective solution. PMID- 27402543 TI - Assent Described: Exploring Perspectives From the Inside. AB - PURPOSE: The purpose of this study was to describe the informed consent and assent experience for oncology research from the perspective of the participants: adolescents, their parents, and their physician providers. DESIGN & METHODS: This descriptive mixed-methods study included the pilot use of the Quality of Informed Consent Questionnaire (QuIC) with an adolescent population and semi-structured interviews with adolescents, their parents, and their physician providers within 48-72 hours of the informed consent and assent discussion for a pediatric oncology clinical trial and again 6-9 weeks later. RESULTS: Adolescents and their parents scored considerably lower on part A of the QuIC than part B indicating a lower level of objective understanding of key elements of informed consent and assent. Qualitative interviews highlight participants' self-reported poor memory or recollection of key details of the informed consent and assent discussion paralleling the QuIC findings for objective understanding. CONCLUSION: Findings from this pilot descriptive study suggest that adolescents and their parents feel more informed than they actually are. This dichotomy of experience seems to have been mitigated by a strong sense of trust in and connection with their physician provider. PRACTICE IMPLICATIONS: Further exploration of adolescent and parent viewpoints regarding what they value as important in the content of the informed consent and assent and how that content is delivered is warranted. Additionally, understanding the origin of participants' misunderstanding of the key elements of consent and assent may illuminate areas for future intervention-based research focused on improving the overall quality of informed consent and assent discussions. PMID- 27402546 TI - The big health data sale: As the trade of personal health and medical data expands, it becomes necessary to improve legal frameworks for protecting patient anonymity, handling consent and ensuring the quality of data. PMID- 27402544 TI - FATE1 antagonizes calcium- and drug-induced apoptosis by uncoupling ER and mitochondria. AB - Several stimuli induce programmed cell death by increasing Ca(2+) transfer from the endoplasmic reticulum (ER) to mitochondria. Perturbation of this process has a special relevance in pathologies as cancer and neurodegenerative disorders. Mitochondrial Ca(2+) uptake mainly takes place in correspondence of mitochondria associated ER membranes (MAM), specialized contact sites between the two organelles. Here, we show the important role of FATE1, a cancer-testis antigen, in the regulation of ER-mitochondria distance and Ca(2+) uptake by mitochondria. FATE1 is localized at the interface between ER and mitochondria, fractionating into MAM FATE1 expression in adrenocortical carcinoma (ACC) cells under the control of the transcription factor SF-1 decreases ER-mitochondria contact and mitochondrial Ca(2+) uptake, while its knockdown has an opposite effect. FATE1 also decreases sensitivity to mitochondrial Ca(2+)-dependent pro-apoptotic stimuli and to the chemotherapeutic drug mitotane. In patients with ACC, FATE1 expression in their tumor is inversely correlated with their overall survival. These results show that the ER-mitochondria uncoupling activity of FATE1 is harnessed by cancer cells to escape apoptotic death and resist the action of chemotherapeutic drugs. PMID- 27402547 TI - Research in space: in search of meaning: Life science research aboard the International Space Station has come under scrutiny for its costs and apparent lack of returns. PMID- 27402545 TI - CTRL+INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome. AB - The human genome contains millions of fragments from retrotransposons-highly repetitive DNA sequences that were once able to "copy and paste" themselves to other regions in the genome. However, the majority of retrotransposons have lost this capacity through acquisition of mutations or through endogenous silencing mechanisms. Without this imminent threat of transposition, retrotransposons have the potential to act as a major source of genomic innovation. Indeed, large numbers of retrotransposons have been found to be active in specific contexts: as gene regulatory elements and promoters for protein-coding genes or long noncoding RNAs, among others. In this review, we summarise recent findings about retrotransposons, with implications in gene expression regulation, the expansion of gene isoform diversity and the generation of long noncoding RNAs. We highlight key examples that demonstrate their role in cellular identity and their versatility as markers of cell states, and we discuss how their dysregulation may contribute to the formation of and possibly therapeutic response in human cancers. PMID- 27402548 TI - Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response. AB - microRNAs (miRNAs), the tiny but stable regulatory RNAs in metazoan cells, can undergo selective turnover in presence of specific internal and external cues to control cellular response against the changing environment. We have observed reduction in cellular miR-122 content, due to their accelerated extracellular export in human hepatic cells starved for small metabolites including amino acids. In this context, a new role of human ELAV protein HuR has been identified. HuR, a negative regulator of miRNA function, accelerates extracellular vesicle (EV)-mediated export of miRNAs in human cells. In stressed cells, HuR replaces miRNPs from target messages and is both necessary and sufficient for the extracellular export of corresponding miRNAs. HuR could reversibly bind miRNAs to replace them from Ago2 and subsequently itself gets freed from bound miRNAs upon ubiquitination. The ubiquitinated form of HuR is predominantly associated with multivesicular bodies (MVB) where HuR-unbound miRNAs also reside. These MVB associated pool of miRNAs get exported out via EVs thereby delimiting cellular miR-122 level during starvation. Therefore, by modulating extracellular export of miR-122, HuR could control stress response in starved human hepatic cells. PMID- 27402549 TI - Housing Quality in a Randomized Controlled Trial of Housing First for Homeless Individuals with Mental Illness: Correlates and Associations with Outcomes. AB - Housing quality (HQ) is associated with mental health, and may mediate outcomes in housing interventions. However, studies of housing interventions rarely report HQ. The purpose of this study was to describe HQ in a multi-site randomized controlled trial of Housing First (HF) in five Canadian cities and to examine possible differences by treatment group (HF recipients and treatment-as-usual (TAU) participants who were able to find housing through other programs or on their own). We also examined the association between HQ and the primary trial outcome: housing stability. The performance of a new multi-dimensional standardized observer-rated housing quality scale (the OHQS) in a relatively large cross-site sample was also of interest. HQ was rated by trained research assistants for 204 HF participants and 228 TAU participants using the OHQS. General linear regression models were used to examine unit/building quality scores by group and site adjusting for other group differences, and as a predictor of housing stability outcomes after 24 months of follow-up. The OHQS was found to have good reliability and validity, but because most of the neighborhood subscale items were negatively correlated with the overall scale, only unit and building items were included in the total HQ score (possible scores ranging from 13.5 to 135). Unit/building HQ was significantly better for the HF group overall (91.2 (95 % CI = 89.6-92.9) vs. 88.3 (95 % CI = 86.1-90.5); p = .036), and in one site. HQ in the TAU group was much more variable than the HF group overall (W (mean) = 24.7; p < .001) and in four of five sites. Unit/building HQ scores were positively associated with housing stability: (73.4 (95 % CI 68.3-78.5) for those housed none of the time; 91.1 (95 % CI 89.2-93.0) for those housed some of the time; and 93.1 (95 % CI 91.4-94.9)) for those housed all of the time (F = 43.9 p < .001). This association held after adjusting for site, housing characteristics, participant ethnocultural status, community functioning, and social support. This study demonstrates that HQ can be as good or better, and less variable, in HF programs in Canada that systematically and predominantly source housing stock from the private sector compared to housing procured outside of an HF program. HQ is also an important predictor of housing stability outcomes. PMID- 27402550 TI - A content analysis of tweets about high-potency marijuana. AB - INTRODUCTION: "Dabbing" involves heating extremely concentrated forms of marijuana to high temperatures and inhaling the resulting vapor. We studied themes describing the consequences of using highly concentrated marijuana by examining the dabbing-related content on Twitter. METHODS: Tweets containing dabbing-related keywords were collected from 1/1-1/31/2015 (n=206,854). A random sample of 5000 tweets was coded for content according to pre-determined categories about dabbing-related behaviors and effects experienced using a crowdsourcing service. An examination of tweets from the full sample about respiratory effects and passing out was then conducted by selecting tweets with relevant keywords. RESULTS: Among the 5000 randomly sampled tweets, 3540 (71%) were related to dabbing marijuana concentrates. The most common themes included mentioning current use of concentrates (n=849; 24%), the intense high and/or extreme effects from dabbing (n=763; 22%) and excessive/heavy dabbing (n=517; 15%). Extreme effects included both physiological (n=124/333; 37%) and psychological effects (n=55/333; 17%). The most common physiologic effects, passing out (n=46/333; 14%) and respiratory effects (n=30/333; 9%), were then further studied in the full sample of tweets. Coughing was the most common respiratory effect mentioned (n=807/1179; 68%), and tweeters commonly expressed dabbing with intentions to pass out (416/915; 45%). CONCLUSIONS: This study adds to the limited understanding of marijuana concentrates and highlights self reported physical and psychological effects from this type of marijuana use. Future research should further examine these effects and the potential severity of health consequences associated with concentrates. PMID- 27402551 TI - Validation of a substance and alcohol use assessment instrument among orphans and vulnerable children in Zambia using Audio Computer Assisted Self-Interviewing (ACASI). AB - BACKGROUND: Substance and alcohol misuse is a global problem that increases the risk of HIV infection. This is a concern among orphans and vulnerable children (OVC) in sub-Saharan Africa who may have elevated substance use rates. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) is a reliable and valid instrument of substance use among adults in primary care high-income settings. This study examined psychometric properties of the ASSIST among OVC in Zambia using Audio Computer Assisted Self-Interviewing (ACASI). METHODS: Baseline data from an ongoing randomized trial of interventions to reduce HIV risk behaviors were analyzed. The analysis included 502 OVC ages 13-17 living in low income, high-density neighborhoods in Lusaka, Zambia. Internal consistency of the ASSIST was assessed and discriminant validity was measured using items from the Youth Self Report as criterion variables. RESULTS: Internal reliability was strong with a Cronbach's alpha of >=0.80 for each of the specific substance scales and total substance involvement. For all substances except tobacco and sedatives, discriminant validity was demonstrated in distinguishing between low risk use and moderate use. Sensitivity and specificity analysis indicated adequate area under the curve across substance types (AUC range: 0.68-0.80). Discrimination between moderate and high risk was demonstrated for alcohol and total substance involvement. CONCLUSIONS: ASSIST administered via ACASI is a reliable instrument and an appropriate tool for distinguishing between low and hazardous substance use among adolescent OVC populations in sub-Saharan Africa. Additional examination is warranted to determine its ability to measure gradations of severity within hazardous use. PMID- 27402552 TI - Betatrophin: no relation to glucose metabolism or weight status in obese children before and after lifestyle intervention. AB - OBJECTIVE: The influences of obesity, glucose metabolism, gender, and puberty on betatrophin levels and the longitudinal relationships between weight loss, metabolic changes and betatrophin have not yet been studied in childhood. METHODS: Cross-sectional and longitudinal analysis of weight status (standard deviation score-body mass index (SDS-BMI)), homeostasis model assessment insulin resistance (HOMA-IR), gender, and pubertal stage were evaluated in 69 obese children (51% female, age 11.9 +/- 2.0 years) participating in lifestyle intervention over a 1-year period. An oral glucose tolerance test was performed in 53 of the 69 children. Twenty normal weight children (50% female, age 12.3 +/- 3.0 years) served as controls. RESULTS: Circulating betatrophin did not differ significantly between obese and lean children (1.99 +/- 0.90 vs 2.35 +/- 0.28, mean +/- SD, P = .155). At baseline, betatrophin did not differ in obese patients with vs without glucose intolerance (1.89 +/- 0.96 vs 2.031 +/- 0.91 ng/mL; P = .591) and obese with (delta SDS-BMI >0.4) vs without successful obesity intervention (1.89 +/- 0.94 vs. 2.07 +/- 0.87 ng/mL; P = 0.396). In multiple linear regression analyses, pubertal stage was associated with betatrophin (b: 0.48, P = .027), while gender, age, BMI, blood pressure, fasting glucose, HOMA IR, triglycerides, LDL- and HDL-cholesterol were not related to betatrophin at baseline. At the end of the 1-year intervention, changes of betatrophin were not significantly associated with any parameter after controlling for multiple covariates including age and changes of pubertal stages. CONCLUSIONS: Our data do not support a relationship between betatrophin and weight status or glucose tolerance, insulin resistance, and lipid metabolism in children. PMID- 27402554 TI - Untangling the neurobiology of coping styles in rodents: Towards neural mechanisms underlying individual differences in disease susceptibility. AB - Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding of coping style variation is fundamental for biobehavioral neurosciences in probing individual disease susceptibility. This review outlines individual differences in trait aggressiveness as an adaptive component of the natural sociobiology of rats and mice, and highlights that these reflect the general style of coping that varies from proactive (aggressive) to reactive (docile). We propose that this qualitative coping style can be disentangled into multiple quantitative behavioral domains, e.g., flexibility/impulse control, emotional reactivity and harm avoidance/reward processing, that each are encoded into selective neural circuitries. Since functioning of all these brain circuitries rely on fine-tuned serotonin signaling, autoinhibitory control mechanisms of serotonergic neuron (re)activity are crucial in orchestrating general coping style. Untangling the precise neuromolecular mechanisms of different coping styles will provide a roadmap for developing better therapeutic strategies of stress-related diseases. PMID- 27402555 TI - Light stability tests of CH3NH3PbI3 perovskite solar cells using porous carbon counter electrodes. AB - The CH3NH3PbI3 perovskite solar cells have been fabricated using three-porous layered electrodes as, for light stability tests. Without encapsulation in air, the CH3NH3PbI3 perovskite solar cells maintained 80% of photoenergy conversion efficiency from the initial value up to 100 h under light irradiation (AM 1.5, 100 mW cm-2). Considering the color variation of the CH3NH3PbI3 perovskite layer, the significant improvement of light stability is due to the moisture-blocking effect of the porous carbon back electrodes. The strong interaction between carbon and CH3NH3PbI3 perovskite was proposed by the measurements of X-ray photoelectron spectroscopy and X-ray diffraction of the porous carbon-perovskite layers. PMID- 27402553 TI - Chemotherapy-induced damage to ovary: mechanisms and clinical impact. AB - Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility. PMID- 27402556 TI - The effect of 1 year of Alagebrium and moderate-intensity exercise training on left ventricular function during exercise in seniors: a randomized controlled trial. AB - Sedentary aging leads to left ventricular (LV) and vascular stiffening due in part to advanced glycation end-products (AGEs) cross-linking of extracellular matrix proteins. Vigorous lifelong exercise ameliorates age-related cardiovascular (CV) stiffening and enhances exercise LV function, although this effect is limited when exercise is initiated later in life. We hypothesized that exercise training might be more effective at improving the impact of age-related CV stiffening during exercise when combined with an AGE cross-link breaker (Alagebrium). Sixty-two seniors (>=60 yr) were randomized into four groups: sedentary + placebo, sedentary + Alagebrium, exercise + placebo, and exercise + Alagebrium for 1 yr. Moderate-intensity aerobic exercise was performed 3-4 sessions/wk; controls underwent similar frequency of yoga/balance training. Twenty-four similarly-aged, lifelong exercisers (4-5 sessions/wk) served as a comparator for the effect of lifelong exercise on exercising LV function. Oxygen uptake (Douglas bags), stroke index (SI; acetylene rebreathing), and effective arterial elastance (Ea) were collected at rest and submaximal and maximal exercise. Maximum O2 uptake (23 +/- 5 to 25 +/- 6 ml.kg(-1).min(-1)) increased, while SI (35 +/- 11 to 39 +/- 12 ml/m(2)) and Ea (4.0 +/- 1.1 to 3.7 +/- 1.2 mmHg.ml(-1).m(-2)) were improved across all conditions with exercise, but remained unchanged in controls (exercise * time, P <= 0.018). SI or Ea were not affected by Alagebrium (medication * time, P >= 0.468) or its combination with exercise (interaction P >= 0.252). After 1 yr of exercise plus Alagebrium, exercise SI and Ea remained substantially below that of lifelong exercisers (15 24 and 9-22%, respectively, P <= 0.415). In conclusion, Alagebrium plus exercise had no synergistic effect on exercise LV function and failed to achieve levels associated with lifelong exercise, despite a similar exercise frequency. PMID- 27402557 TI - Evaluating the control: minipump implantation and breathing behavior in the neonatal rat. AB - We evaluated genioglossus (GG) gross motoneuron morphology, electromyographic (EMG) activities, and respiratory patterning in rat pups allowed to develop without interference (unexposed) and pups born to dams subjected to osmotic minipump implantation in utero (saline-exposed). In experiment 1, 48 Sprague Dawley rat pups (Charles-River Laboratories), ages postnatal day 7 (P7) through postnatal day 10 (P10), were drawn from two experimental groups, saline-exposed (n = 24) and unexposed (n = 24), and studied on P7, P8, P9, or P10. Pups in both groups were sedated (Inactin hydrate, 70 mg/kg), and fine-wire electrodes were inserted into the GG muscle of the tongue and intercostal muscles to record EMG activities during breathing in air and at three levels of normoxic hypercapnia [inspired CO2 fraction (FiCO2 ): 0.03, 0.06, and 0.09]. Using this approach, we assessed breathing frequency, heart rate, apnea type, respiratory event types, and respiratory stability. In experiment 2, 16 rat pups were drawn from the same experimental groups, saline-exposed (n = 9) and unexposed (n = 7), and used in motoneuron-labeling studies. In these pups a retrograde dye was injected into the GG muscle, and the brain stems were subsequently harvested and sliced. Labeled GG motoneurons were identified with microscopy, impaled, and filled with Lucifer yellow. Double-labeled motoneurons were reconstructed, and the number of primary projections and soma volumes were calculated. Whereas pups in each group exhibited the same number (P = 0.226) and duration (P = 0.093) of respiratory event types and comparable motoneuron morphologies, pups in the implant group exhibited more central apneas and respiratory instability relative to pups allowed to develop without interference. PMID- 27402558 TI - Correcting the dynamic response of a commercial esophageal balloon-catheter. AB - It is generally recommended that an esophageal balloon-catheter possess an adequate frequency response up to 15 Hz, such that parameters of respiratory mechanics may be quantified with precision. In our experience, however, we have observed that some commercially available systems do not display an ideal frequency response (<8-10 Hz). We therefore investigated whether the poor frequency response of a commercially available esophageal catheter may be adequately compensated using two numerical techniques: 1) an exponential model correction, and 2) Wiener deconvolution. These two numerical techniques were performed on a commercial balloon-catheter interfaced with 0, 1, and 2 lengths of extension tubing (90 cm each), referred to as configurations L0, L90, and L180, respectively. The frequency response of the balloon-catheter in these configurations was assessed by empirical transfer function analysis, and its "working" range was defined as the frequency beyond which more than 5% amplitude and/or phase distortion was observed. The working frequency range of the uncorrected balloon-catheter extended up to only 10 Hz for L0, and progressively worsened with additional tubing length (L90 = 3 Hz, L180 = 2 Hz). Although both numerical methods of correction adequately enhanced the working frequency range of the balloon-catheter to beyond 25 Hz for all length configurations (L0, L90, and L180), Wiener deconvolution consistently provided more accurate corrections. Our data indicate that Wiener deconvolution provides a superior correction of the balloon-catheter's dynamic response, and is relatively more robust to extensions in catheter tube length compared with the exponential correction method. PMID- 27402559 TI - Predicting metabolic rate during level and uphill outdoor walking using a low cost GPS receiver. AB - The objective of this study was to assess the accuracy of using speed and grade data obtained from a low-cost global positioning system (GPS) receiver to estimate metabolic rate (MR) during level and uphill outdoor walking. Thirty young, healthy adults performed randomized outdoor walking for 6-min periods at 2.0, 3.5, and 5.0 km/h and on three different grades: 1) level walking, 2) uphill walking on a 3.7% mean grade, and 3) uphill walking on a 10.8% mean grade. The reference MR [metabolic equivalents (METs) and oxygen uptake (Vo2)] values were obtained using a portable metabolic system. The speed and grade were obtained using a low-cost GPS receiver (1-Hz recording). The GPS grade (Delta altitude/distance walked) was calculated using both uncorrected GPS altitude data and GPS altitude data corrected with map projection software. The accuracy of predictions using reference speed and grade (actual[SPEED/GRADE]) data was high [R(2) = 0.85, root-mean-square error (RMSE) = 0.68 MET]. The accuracy decreased when GPS speed and uncorrected grade (GPS[UNCORRECTED]) data were used, although it remained substantial (R(2) = 0.66, RMSE = 1.00 MET). The accuracy was greatly improved when the GPS speed and corrected grade (GPS[CORRECTED]) data were used (R(2) = 0.82, RMSE = 0.79 MET). Published predictive equations for walking MR were also cross-validated using actual or GPS speed and grade data when appropriate. The prediction accuracy was very close when either actual[SPEED/GRADE] values or GPS[CORRECTED] values (for level and uphill combined) or GPS speed values (for level walking only) were used. These results offer promising research and clinical applications related to the assessment of energy expenditure during free-living walking. PMID- 27402560 TI - Intermuscular adipose tissue and thigh muscle area dynamics during an 18-month randomized weight loss trial. AB - It remains unclear whether intermuscular adipose tissue (IMAT) has any metabolic influence or whether it is merely a marker of abnormalities, as well as what are the effects of specific lifestyle strategies for weight loss on the dynamics of both IMAT and thigh muscle area (TMA). We followed the trajectory of IMAT and TMA during 18-mo lifestyle intervention among 278 sedentary participants with abdominal obesity, using magnetic resonance imaging. We measured the resting metabolic rate (RMR) by an indirect calorimeter. Among 273 eligible participants (47.8 +/- 9.3 yr of age), the mean IMAT was 9.6 +/- 4.6 cm(2) Baseline IMAT levels were directly correlated with waist circumference, abdominal subdepots, C reactive protein, and leptin and inversely correlated with baseline TMA and creatinine (P < 0.05 for all). After 18 mo (86.3% adherence), both IMAT (-1.6%) and TMA (-3.3%) significantly decreased (P < 0.01 vs. baseline). The changes in both IMAT and TMA were similar across the lifestyle intervention groups and directly corresponded with moderate weight loss (P < 0.001). IMAT change did not remain independently associated with decreased abdominal subdepots or improved cardiometabolic parameters after adjustments for age, sex, and 18-mo weight loss. In similar models, 18-mo TMA loss remained associated with decreased RMR, decreased activity, and with increased fasting glucose levels and IMAT (P < 0.05 for all). Unlike other fat depots, IMAT may not represent a unique or specific adipose tissue, instead largely reflecting body weight change per se. Moderate weight loss induced a significant decrease in thigh muscle area, suggesting the importance of resistance training to accompany weight loss programs. PMID- 27402561 TI - Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system. AB - We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2(+/+)) and tryptophan hydroxylase 2 knockout (Tph2(-/-)) mice. Following a C2 hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i.e., sham protocol, 21% oxygen) for 10 consecutive days. Diaphragm activity recovered to prehemisection levels in the Tph2(+/+) and Tph2(-/-) mice following exposure to IH but not normoxia [Tph2(+/+) 1.3 +/- 0.2 (SE) vs. 0.3 +/- 0.2; Tph2(-/-) 1.06 +/- 0.1 vs. 0.3 +/- 0.1, standardized to prehemisection values, P < 0.01]. Likewise, recovery of tidal volume and breathing frequency was evident, although breathing frequency values did not return to prehemisection levels within the time frame of the protocol. Partial recovery of limb motor function was also evident 2 wk after spinal cord hemisection. However, recovery was not dependent on IH or the presence of serotonin in the central nervous system. We conclude that IH promotes recovery of respiratory function but not basic motor tasks. Moreover, we conclude that spontaneous or treatment-induced recovery of respiratory and motor limb function is not dependent on serotonin in the central nervous system in a mouse model of spinal cord injury. PMID- 27402563 TI - Neuropeptide Y expression confers benzo[a]pyrene induced anxiolytic like behavioral response during early adolescence period of male Wistar rats. AB - Environmental neurotoxicant like benzo[a]pyrene (B[a]P) is known to induce neurobehavioral changes. Our previous reports address the adverse effect of B[a]P on the neurobehavioral responses and neuromorphology of sensitive brain regions in adolescent rats. Present study was conducted on male Wistar rat neonates at postnatal day 5 (PND5) to ascertain B[a]P induced anxiolytic like behavioral response could be an outcome of neuropeptide Y (NPY) overexpression in brain. Single intracisternal administration of B[a]P was carried out at PND5 to elucidate the role of NPY on neurobehavioral responses at PND30. The behavioral studies showed anxiolytic like effect of B[a]P in both light and dark box and elevated plus maze tests. Antioxidant assay involving glutathione peroxidase activity was significantly decreased where as lipid peroxidation was significantly augmented in both hippocampus and hypothalamus of B[a]P treated group as compared to naive and control. The neurotransmitter estimation by HPLC ECD showed significant increase in 5-HT level in both hippocampus and hypothalamus of B[a]P treated group. Significant elevation in NPY expression was observed in both hippocampus and hypothalamus of B[a]P group. Intracellular Ca2+ estimation using Fura-2AM by fluorometry showed that B[a]P induced increase in Ca2+ influx was associated with augmented NPY expression in brain. As NPY has orexigenic effect, our result revealed that there was a significant increase in body weight at PND30 following B[a]P administration to rat neonates at PND5. These findings suggested that NPY overexpression in brain regions might be associated with anxiolytic like behavioral response and orexigenic effect in rats following single intracisternal B[a]P administration. Future research directing towards understanding the signaling cascades of B[a]P induced biochemical and neuromorphological alteration might address the independent pathway which induce neurodegeneration despite NPY overexpression in brain regions of adolescent rats. PMID- 27402564 TI - The effect of magnesium as activator and inhibitor of anaerobic digestion. AB - Anaerobic digestion stands as a key technology in the emerging green energy economy. Mg(2+) has been identified as an important element to improve digesters methane production; however the inhibition risk that high Mg(2+) concentrations can cause to the AD process must also be considered when dosing Mg reagents and wastes containing Mg(2+). Despite its importance, Mg(2+) stimulation and inhibition mechanisms as well as threshold values are scarce in the literature. This research paper investigates the impact (stimulation and inhibition) of Mg(2+) on pig manure anaerobic digestion. Mathematical modelling was used to better understand the interaction between substrate, inoculum and magnesium, where Mg(2+) inhibition was modelled by a n-component non-competitive inhibition function. Modelling was done on absolute curves rather than specific methane productions curves (new approach) to account for the lower background methane production of the inoculum as the Mg(2+) concentration increased. Results showed that no stimulation or inhibition occurred between 40 (native concentration) and 400mgMg(2+)L(-1), while minor and major inhibition were observed at 750 and 1000mgMg(2+)L(-1), and at 2000 and 4000mgMg(2+)L(-1), respectively. Mg(2+) half maximal inhibition concentration was estimated at 2140mgMg(2+)L(-1) with an inhibition order of 2. The latter indicates that Mg(2+) inhibition is a progressive rather than a steep inhibition mechanism. PMID- 27402562 TI - Effect of betamethasone, surfactant, and positive end-expiratory pressures on lung aeration at birth in preterm rabbits. AB - Antenatal glucocorticoids, exogenous surfactant, and positive end-expiratory pressure (PEEP) ventilation are commonly provided to preterm infants to enhance respiratory function after birth. It is unclear how these treatments interact to improve the transition to air-breathing at birth. We investigated the relative contribution of antenatal betamethasone, prophylactic surfactant, and PEEP (3 cmH2O) on functional residual capacity (FRC) and dynamic lung compliance (CDL) in preterm (28 day GA) rabbit kittens at birth. Kittens were delivered by cesarean section and mechanically ventilated. FRC was calculated from X-ray images, and CDL was measured using plethysmography. Without betamethasone, PEEP increased FRC recruitment and CDL Surfactant did not further increase FRC, but significantly increased CDL Betamethasone abolished the benefit of PEEP on FRC, but surfactant counteracted this effect of betamethasone. These findings indicate that low PEEP levels are insufficient to establish FRC at birth following betamethasone treatment. However, surfactant reversed the effect of betamethasone and when combined, these two treatments enhanced FRC recruitment irrespective of PEEP level. PMID- 27402565 TI - Progress towards achieving hepatitis B control in the Cook Islands, Niue, Tokelau, and Kiribati. AB - BACKGROUND: Hepatitis B virus (HBV) is highly endemic in many of the Pacific Island countries. Four island countries-Cook Islands, Kiribati, Niue, and Tokelau sought to evaluate the success of their hepatitis B vaccination programs by conducting nationally representative serosurveys among children born post-vaccine introduction. METHODS: Cook Islands, Niue, and Tokelau conducted school-based census serosurveys because of small populations. The Cook Islands tested children in second grade; Niue tested children in early childhood education through sixth grade; and Tokelau tested children in first through sixth grades. Because Kiribati has a much larger birth cohort, it conducted a one-stage stratified serosurvey among first grade students. All four countries tested children using the Alere DetermineTM rapid point of care hepatitis B surface antigen (HBsAg) test. RESULTS: In the three smaller countries, no children were seropositive for HBsAg (0/245 Cook Island students, 0/183 Niuean students, 0/171 Tokelau students). In Kiribati, 39 (3.3%, 95% confidence interval 2.4-4.6%) of 1249 students were HBsAg positive. Vaccination data collected in the Cook Islands and Tokelau showed high vaccination coverage in both countries with ?95% birth dose coverage and 100% 3-dose coverage. CONCLUSIONS: The Cook Islands, Niue, and Tokelau have made remarkable progress in establishing strong vaccination programs and towards decreasing the burden of hepatitis B among children. Kiribati still needs to improve vaccination coverage to achieve the <1% HBsAg target established by the World Health Organization Western Pacific Region. PMID- 27402567 TI - New Author Benefits from Evolution & Development. PMID- 27402568 TI - Embryonic development of the larval eyes of the Sunburst Diving Beetle, Thermonectus marmoratus (Insecta: Dytiscidae): a morphological study. AB - Stemmata, the larval eyes of holometabolous insects are extremely diverse, ranging from full compound eyes, to a few ommatidial units as are typical in compound eyes, to sophisticated and functionally specialized image-forming camera type eyes. Stemmata evolved from a compound eye ommatidial ancestor, an eye type that is morphologically well conserved in regards to cellular composition, and well studied in regards to development. However, despite this evolutionary origin it remains largely unknown how stemmata develop. In addition, it is completely unclear how development is altered to give rise to some of the functionally most complex stemmata, such as those of the sunburst diving beetle, Thermonectus marmoratus. In this study, we used histological methods to investigate the embryonic development of the functionally complex principal stemmata Eye 1 and Eye 2 of the larval visual system of T. marmoratus. To gain insights into how cellular components of their sophisticated camera-type eyes might have evolved from the cellular components of ommatidial ancestors, we contrast our findings against known features of ommatidia development, which are particularly well understood in Drosophila. We find many similarities, such as the early presence of a pseudostratified epithelium, and the order in which specific cell types are recruited. However, in Thermonectus each cell type is represented by a large number of cells from early on and major tissue re-orientation occurs as eye development progresses. This study provides insights into the timing of morphological features and represents the basis for future molecular studies. PMID- 27402569 TI - Evolution of organogenesis and the origin of altriciality in mammals. AB - Mammals feature not only great phenotypic disparity, but also diverse growth and life history patterns, especially in maturity level at birth, ranging from altriciality to precocity. Gestation length, morphology at birth, and other markers of life history are fundamental to our understanding of mammalian evolution. Based on the first synthesis of embryological data and the study of new ontogenetic series, we reconstructed estimates of the ancestral chronology of organogenesis and life-history modes in placental mammals. We found that the ancestor of marsupial and placental mammals was placental-like at birth but had a long, marsupial-like infancy. We hypothesize that mammalian viviparity might have evolved in association with the extension of growth after birth, enabled through lactation, and that mammalian altriciality is inherited from the earliest amniotes. The precocial lifestyle of extant sauropsids and that of many placental mammals were acquired secondarily. We base our conclusions on the best estimates and provide a comprehensive discussion on the methods used and the limitations of our dataset. We provide the most comprehensive embryological dataset ever published, "rescue" old literature sources, and apply available methods and illustrate thus an approach on how to investigate comparatively organogenesis in macroevolution. PMID- 27402566 TI - Evaluation of novel synthetic TLR7/8 agonists as vaccine adjuvants. AB - Small-molecule adjuvants that boost and direct adaptive immunity provide a powerful means to increase the effectiveness of vaccines. Through rational design several novel imidazoquinoline and oxoadenine TLR7/8 agonists, each with unique molecular modifications, were synthesized and assessed for their ability to augment adaptive immunity. All agonists bound human TLR7 and TLR8 and induced maturation of both human mDCs and pDCs. All agonists prompted production of type I interferon and/or proinflammatory cytokines, albeit with varying potencies. In most in vitro assays, the oxoadenine class of agonists proved more potent than the imidazoquinolines. Therefore, an optimized oxoadenine TLR7/8 agonist that demonstrated maximal activity in the in vitro assays was further assessed in a vaccine study with the CRM197 antigen in a porcine model. Antigen-specific antibody production was greatly enhanced in a dose dependent manner, with antibody titers increased 800-fold compared to titers from pigs vaccinated with the non-adjuvanted vaccine. Moreover, pigs vaccinated with antigen containing the highest dose of adjuvant promoted a 13-fold increase in the percentage of antigen specific CD3(+)/CD8(+) T cells over pigs vaccinated with antigen alone. Together this work demonstrates the promise of these novel TLR7/8 agonists as effective human vaccine adjuvants. PMID- 27402570 TI - Juvenile social status predicts primary sex allocation in a sex changing fish. AB - Both individual sex and population sex ratio can affect lifetime reproductive success. As a result, multiple mechanisms have evolved to regulate sexual phenotype, including adult sex change in fishes. While adult sex change is typically socially regulated, few studies focus on the non-chromosomal mechanisms regulating primary sex allocation. We investigated primary sex determination in the bluebanded goby (Lythrypnus dalli), a bidirectionally sex-changing fish. Of the studies investigating primary sex determination in species with adult sex change, this is the first to incorporate the roles of social status and size, key factors for determining adult sex allocation. For L. dalli, adult sex is regulated by social status: dominants are male; subordinates are female. In social groups of laboratory-reared juveniles, we demonstrate that status also predicts primary sex. Dominant juveniles developed male-typical genitalia, and their gonads contained significantly less ovarian tissue than subordinates, which developed female-typical genitalia. To better understand natural development, we quantified the distribution of juveniles and adults on the reef and analyzed genital papilla and gonad morphology in a sample of wild-caught juveniles. Juveniles were observed in various social environments, and most grouped with other juveniles and/or adults. The majority of field-caught juveniles had female typical genitalia and bisexual, female-biased gonads. These data are consistent with a single mechanism that regulates sexual phenotype throughout life. Social status could first cause and then maintain through adulthood a female-biased population, allowing individuals to regulate sex based on local conditions, which is important for optimizing lifetime reproductive success. PMID- 27402571 TI - Expression of GATA and POU transcription factors during the development of the planktotrophic trochophore of the polychaete serpulid Hydroides elegans. AB - The expression of transcription factors with endodermal and mesodermal roles in bilaterians is characterized during the development of Hydroides elegans, a serpulid polychaete with planktotrophic trochophore. GATA 4/5/6 is expressed in endodermal and mesodermal precursors during embryogenesis and in the midgut of trochophore larvae. HeGATA1/2/3a is expressed in animal hemisphere blastomeres 1d121 and 1d122, in dorsal ectoderm and in 4d endomesodermal derivatives that maintain their expression in trochophore larvae. HeGATA1/2/3b is not expressed during embryogenesis, but in several regions of the larva during postembryonic development. During very early gastrulation, Brn1/2/4 is first expressed in cells associated with the prospective oral/foregut side of the blastopore, and during larval development in 4d blastomere descendants. Comparison with orthologs in other metazoans suggests ancestral expression of GATA4/5/6 in the midgut of the last common ancestor of protostomes and deuterostomes. The conserved expression of Brn1/2/4 in the foregut precursors of Hydroides and sea urchins suggests an ancestral role in patterning the tripartite gut of planktotrophic larvae. Broader analysis of these and other regulatory genes reveals variability of developmental gene expression among polychaetes with lecithotrophic larvae, suggesting that they are evolutionarily derived from polychaetes with planktotrophic larvae. PMID- 27402572 TI - The diversity of nanos expression in echinoderm embryos supports different mechanisms in germ cell specification. AB - Specification of the germ cell lineage is required for sexual reproduction in all animals. However, the timing and mechanisms of germ cell specification is remarkably diverse in animal development. Echinoderms, such as sea urchins and sea stars, are excellent model systems to study the molecular and cellular mechanisms that contribute to germ cell specification. In several echinoderm embryos tested, the germ cell factor Vasa accumulates broadly during early development and is restricted after gastrulation to cells that contribute to the germ cell lineage. In the sea urchin, however, the germ cell factor Vasa is restricted to a specific lineage by the 32-cell stage. We therefore hypothesized that the germ cell specification program in the sea urchin/Euechinoid lineage has evolved to an earlier developmental time point. To test this hypothesis we determined the expression pattern of a second germ cell factor, Nanos, in four out of five extant echinoderm clades. Here we find that Nanos mRNA does not accumulate until the blastula stage or later during the development of all other echinoderm embryos except those that belong to the Echinoid lineage. Instead, Nanos is expressed in a restricted domain at the 32-128 cell stage in Echinoid embryos. Our results support the model that the germ cell specification program underwent a heterochronic shift in the Echinoid lineage. A comparison of Echinoid and non-Echinoid germ cell specification mechanisms will contribute to our understanding of how these mechanisms have changed during animal evolution. PMID- 27402574 TI - [Smart fundoscopy]. PMID- 27402573 TI - Evaluation of Goldmann applanation tonometry, rebound tonometry and dynamic contour tonometry in keratoconus. AB - PURPOSE: To compare the intraocular pressure (IOP) measurements obtained with the rebound tonometry (RT), dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in keratoconic corneas and to investigate the effects of central corneal thickness (CCT) and corneal radius of curvature (CR) on IOP measurements. METHODS: Sixty-three eyes of 63 keratoconus patients were enrolled in this cross sectional study. IOP was measured on each subject always in the same order, ICare RT-Pascal DCT-GAT, after a minimum interval of 10min between measurements. CCT and CR were measured using a rotating Scheimpflug camera before the IOP measurements in all subjects. One way repeated measures ANOVA and Pearson correlation coefficient analysis was used for the statistical assessment. RESULTS: Mean IOP for all enrolled eyes was 11.72+/-2.59mmHg for GAT, 9.34+/ 3.29mmHg for RT, and 15.42+/-3.31mmHg for DCT. There were statistically significant differences among the three tonometers; GAT and RT (P<0.001), GAT and DCT (P<0.001), and RT and DCT (P<0.001). GAT and RT were significantly positively correlated with CCT (r=0.288, P=0.025 and r=0.483, P<0.001, respectively). RT was also significantly positively correlated with CR (r=0.550, P<0.001). DCT was not significantly correlated with CCT (r=0.115, P=0.377) nor CR (r=-0.179, P=0.168). CONCLUSIONS: DCT has overestimated but RT has underestimated IOP readings according to GAT measurements in keratoconic corneas. DCT may be the most appropriate tonometer to use in keratoconus for the measurements of IOP, because DCT do not appear to be dependent upon CCT and CR. PMID- 27402575 TI - Imaging: Follow your PET for guidance. PMID- 27402576 TI - Prevention: RANKLing with breast cancer development. PMID- 27402577 TI - Haematological cancer: Obinutuzumab effective against treatment-refractory NHL. PMID- 27402579 TI - Medical Evaluations Then and Now. AB - The role of medicine for children suspected of having been sexually abused has advanced significantly since the 1980s. Newer tests such as DNA and nucleic acid amplification have added to the detection of perpetrators and disease, respectively. Non-acute examination physical findings are seen in only 5% to 10% of instances. Physical findings regarding the hymen and anus have been found to often be normal variants-findings that some used to regard as signs of sexual abuse. Newer considerations for clinicians include Internet child pornography, human trafficking, and use of video/photographic recording. New technologies such as high definition digital photography and telemedicine help to document abuse in a much improved way than existed several decades ago. Nevertheless, the basic approach of careful history-taking remains a bedrock for the diagnosis of child sexual abuse. PMID- 27402578 TI - Lung cancer: Low-dose CT screening - determining the right interval. PMID- 27402580 TI - Factors Related to Rape Reporting Behavior in Brazil: Examining the Role of Spatio-Temporal Factors. AB - The reporting of rape to police is an important component of this crime to have the criminal justice system involved and, potentially, punish offenders. However, for a number of reasons (fear of retribution, self-blame, etc.), most rapes are not reported to police. Most often, the research investigating this phenomenon considers incident and victim factors with little attention to the spatio temporal factors of the rape. In this study, we consider incident, victim, and spatio-temporal factors relating to rape reporting in Campinas, Brazil. Our primary research question is whether or not the spatio-temporal factors play a significant role in the reporting of rape, over and above incident and victim factors. The subjects under study are women who were admitted to the Women's Integrated Healthcare Center at the State University of Campinas, Brazil, and surveyed by a psychologist or a social worker. Rape reporting to police was measured using a dichotomous variable. Logistic regression was used to predict the probability of rape reporting based on incident, victim, and spatio-temporal factors. Although we find that incident and victim factors matter for rape reporting, spatio-temporal factors (rape/home location and whether the rape was in a private or public place) play an important role in rape reporting, similar to the literature that considers these factors. This result has significant implications for sexual violence education. Only when we know why women decide not to report a rape may we begin to work on strategies to overcome these hurdles. PMID- 27402581 TI - Characteristics and Post-Decision Attitudes of Non-Reporting Sexual Violence Victims. AB - Although the physical and psychological consequences of sexual violence can be severe, many victims do not report the violence to the police force. The current study examined the characteristics and the post-decisional attitude of the non reporting sexual violence victims. In total, 287 victims of sexual violence completed an anonymous online questionnaire that assessed characteristics of the violence, whether or not the crime was reported, reasons for not reporting, and aspects that would have convinced non-reporters to report in retrospect. Eighty percent of the victims did not report the most recent sexual violence incident to the police ( n = 229). Nevertheless, 65% of the non-reporting victims ( n = 148) in retrospect would have reported to the police ("potential reporters"). Specific reasons for non-reporting and incident characteristics appear to relate to the post-decision attitude of non-reporting victims of sexual violence. "Lack of evidence" and "feelings of shame, guilt, and other emotions" appear to be more frequently mentioned by potential reporters as reasons for their decision to not report as compared with the definitive non-reporters. Likewise, being raped or sexually assaulted is predictive of potential reporting. Our findings are useful for policy makers to develop strategies to increase reporting rates of sexual violence victims. PMID- 27402582 TI - An Updated Review of Institutions of Higher Education's Responses to Sexual Assault: Results From a Nationally Representative Sample. AB - It has been more than a decade since Karjane, Fisher, and Cullen reviewed a nationally representative sample of Institutions of Higher Education (IHEs) and documented "sexual assault on college campuses" and "what colleges are doing about it." The current research aimed to examine the current state of IHE's response to campus sexual assault as well as any changes in IHE's response over the previous decade. To this end, the present study provides a comparison of data reported in Karjane et al. and 2015 data from a statistically equivalent sample ( n = 820). IHE's utilization of policies and procedures that reflect recent guidance by the Department of Education's Office for Civil Rights (OCR) and best practices indicated by the 2014 White House Task Force to Protect Students From Sexual Assault are also presented and discussed. PMID- 27402583 TI - Registered Randomized Trials Comparing Generic and Brand-Name Drugs: A Survey. AB - OBJECTIVES: To evaluate the research agenda of registered randomized trials comparing generic and brand-name drugs in terms of who sponsors them, whether they are published promptly, and whether they find favorable results. METHODS: We included randomized trials comparing the safety or efficacy of brand-name vs generic medications that were registered in ClinicalTrials.gov or other registries from January 1, 2000, through July 31, 2015. To identify published articles or results generated from such trials, we searched PubMed, Scopus, Google, and registry databases. Data were compared across sponsorship categories ("inbred" if the compared drugs were owned by the same company or its partners/subsidiaries, "competitive" if the compared drugs were owned by competing companies, and "apparently nonprofit"), and time to publication was evaluated with Cox analysis. RESULTS: We found 207 registered protocols reporting on 186 completed trials. Among those trials, 37 had published their results and another 56 had posted results in registries, for a total of 93 trials with available results. Four years after trial completion, results were available for 64 of 138 trials (46.4%), with substantial differences by sponsor: 70.8% (34 of 48), 28.1% (18 of 64), and 46.2% (12 of 26) of the inbred, competitive, and nonprofit trials, respectively. In multivariate modeling, inbred trials had a 1.73-fold risk of having results available compared with competitive trials (P=.04). Almost all trials reported favorable results, with the exception of 4 (4.3% of the 93 trials with results). CONCLUSION: Despite the importance of generic drugs, relatively few registered randomized trials have compared the health effects of generic vs brand-name medicines, and there is an associated unsatisfactory publication rate and almost ubiquitous favorable results. The overall literature on the topic is at high risk of bias, possibly in favor of generic drugs. Higher nonprofit funding and stronger pressure to register trials and publish results are needed. PMID- 27402584 TI - Levels of CMV-reactive antibodies correlate with the induction of CD28(null) T cells and systemic inflammation in chronic obstructive pulmonary disease (COPD). PMID- 27402585 TI - Unusual association between cardiac, skeletal, urogenital and renal abnormalities. AB - We present a 33-year-old woman with an array of congenital abnormalities. She has been diagnosed with polycystic kidney disease (PCKD) with no detectable mutations in PKD1 or PKD2, spina bifida occulta, thoracic skeletal abnormalities, a uterus didelphys and a patent foramen ovale (PFO). There are several associations reported in the literature that include abnormalities similar to the patient's, but none describe her presentation in its entirety. The MURCS association is characterised by (MU)llerian duct aplasia, (R)enal dysplasia and (C)ervical (S)omite anomalies and goes some way in explaining these condition. Patients with both MURCS and PCKD have not been described in current literature. Through this report, we hope to bring a potential diagnosis to light and provide the patient with an improved understanding of her health. PMID- 27402586 TI - Dermatomyositis as a paraneoplastic phenomenon in ovarian cancer. AB - A 60-year-old woman diagnosed with papillary serous ovarian cancer had Klean-Prep and MRI contrast preoperatively. Afterwards, she developed swelling and an urticarial rash around her eye as she proceeded to have planned debulking surgery. Postoperatively the swelling and rash had spread over her face, neck, back and chest. Dermatology advised a possible allergy to Klean-Prep and MRI contrast. Subsequently over the next few months, the patient became severely debilitated from proximal myopathy of the upper and lower limbs, suffered severe pain restricting mobility and small bowel obstruction. Medical oncologist reviewed the patient, clinically diagnosed dermatomyositis and initiated treatment with high-dose intravenous steroids, resulting in remission of the patient's condition. The main purpose of this study is to describe the severity, diagnostic challenges and underline the clinical significance of dermatomyositis manifestations as a paraneoplastic effect in patients with ovarian cancer. PMID- 27402587 TI - Retroperitoneoscopic pyeloplasty for the management of pelvic-ureteric junction obstruction in horseshoe kidney: our initial experience. AB - Horseshoe kidney (HSK) is the most common congenital renal fusion anomaly with approximate incidence of 1:400 to 1:1000 births. Pelvic-ureteric junction obstruction (PUJO) occurs in 15-33% of patients in this population. Herein, we report our experience of management of PUJO in HSK by retroperitoneoscopic pyeloplasty. PMID- 27402588 TI - Dedifferentiated adenoid cystic carcinoma of the nasopharynx: a rare entity of head and neck cancer. PMID- 27402589 TI - Unexpected coronary arterial calcification and thrombosis late after Kawasaki disease. PMID- 27402590 TI - Predictors of Stroke in Atrial Fibrillation. PMID- 27402591 TI - Infarction Size, Interleukin-6, and Their Interaction Are Predictors of Short Term Stroke Outcome in Young Egyptian Adults. AB - BACKGROUND: A trend of increasing incidence of first-ever cerebral ischemic stroke in young adults has been recently reported. The current study was conducted with the objective of identifying independent predictors of short-term outcome of first-ever cerebral ischemic stroke affecting young Egyptian adults. METHODS: The present hospital-based study included 50 patients, 23 males and 27 females, aged 18-45 years, with first-ever ischemic stroke confirmed by computed tomography (CT) and magnetic resonance imaging. Twenty healthy age- and sex matched random control subjects were included to set the reference laboratory values. Detailed medical, neurological, and laboratory data were collected. Stroke severity and short-term stroke outcome were assessed using the Canadian Neurological Scale and the National Institutes of Health Stroke Scale (NIHSS), respectively. RESULTS: High prevalence of modifiable risk factors was observed in young Egyptian adults affected with first-ever ischemic cerebral stroke. Although all studied risk factors were significantly correlated with NIHSS score, multiple regression analysis revealed that only infarction size (CT size), interleukin-6 (IL-6), and their synergistic interaction were the most important predictors of NIHSS stroke outcome. CONCLUSIONS: IL-6 and infarction size were independent predictors of short-term stroke outcome in young Egyptian adults. Synergistic interaction of IL-6 with infarction size suggests an investigative value for assessing serum IL-6 level and a therapeutic benefit for its reduction during the course of early ischemic stroke treatment. PMID- 27402592 TI - A candidate reference method for serum calcium measurement by inductively coupled plasma mass spectrometry. AB - BACKGROUND: Calcium is an important serum ion which is frequently assayed in clinical laboratories. Since quality assurance requires reference methods, the establishment of a candidate reference method for serum calcium measurement is important. METHOD: An inductively coupled plasma mass spectrometry (ICP-MS) method was developed. Serum samples were spiked gravimetrically with aluminum internal standard, digested with 69% ultrapure nitric acid and diluted to test concentration. Then the (44)Ca/(27)Al ratios were measured by ICP-MS in hydrogen mode. The method was calibrated using 5% nitric acid matrix calibrators and the calibration function was established with bracketing method. RESULTS: The correlation coefficients between the measured (44)Ca/(27)Al ratios and the analyte concentrations ratios were all >0.9999. The coefficients of variation of the measurements were 0.27% and 0.16% for two spiked serum. The analytical recovery was 100.24%. The accuracy of the measurement was also verified through measurement of certified reference materials. Comparison with recognized reference method and international inter-laboratory comparisons gave satisfied results. CONCLUSION: New ICP-MS method is specific, precise, simple, and low in cost, and may be used as a candidate reference method in the standardization of serum calcium measurement. PMID- 27402593 TI - Lipopeptides: a novel antigen repertoire presented by major histocompatibility complex class I molecules. AB - Post-translationally modified peptides, such as those containing either phosphorylated or O-glycosylated serine/threonine residues, may be presented to cytotoxic T lymphocytes (CTLs) by MHC class I molecules. Most of these modified peptides are captured in the MHC class I groove in a similar manner to that for unmodified peptides. N-Myristoylated 5-mer lipopeptides have recently been identified as a novel chemical class of MHC class I-presented antigens. The rhesus classical MHC class I allele, Mamu-B*098, was found to be capable of binding N-myristoylated lipopeptides and presenting them to CTLs. A high resolution X-ray crystallographic analysis of the Mamu-B*098:lipopeptide complex revealed that the myristic group as well as conserved C-terminal serine residue of the lipopeptide ligand functioned as anchors, whereas the short stretch of three amino acid residues located in the middle of the lipopeptides was only exposed externally with the potential to interact directly with specific T-cell receptors. Therefore, the modes of lipopeptide-ligand interactions with MHC class I and with T-cell receptors are novel and fundamentally distinct from that for MHC class I-presented peptides. Another lipopeptide-presenting MHC class I allele has now been identified, leading us to the prediction that MHC class I molecules may be separated on a functional basis into two groups: one presenting long peptides and the other presenting short lipopeptides. Since the N-myristoylation of viral proteins is often linked to pathogenesis, CTLs capable of sensing N myristoylation may serve to control pathogenic viruses, raising the possibility for the development of a new type of lipopeptide vaccine. PMID- 27402595 TI - Sensitivity of gamma-interferon test used in series after tuberculin test to detect bovine tuberculosis. PMID- 27402594 TI - Dishing out mini-brains: Current progress and future prospects in brain organoid research. AB - The ability to model human brain development in vitro represents an important step in our study of developmental processes and neurological disorders. Protocols that utilize human embryonic and induced pluripotent stem cells can now generate organoids which faithfully recapitulate, on a cell-biological and gene expression level, the early period of human embryonic and fetal brain development. In combination with novel gene editing tools, such as CRISPR, these methods represent an unprecedented model system in the field of mammalian neural development. In this review, we focus on the similarities of current organoid methods to in vivo brain development, discuss their limitations and potential improvements, and explore the future venues of brain organoid research. PMID- 27402596 TI - Ghrelin modulates encoding-related brain function without enhancing memory formation in humans. AB - Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. PMID- 27402597 TI - Dual array EEG-fMRI: An approach for motion artifact suppression in EEG recorded simultaneously with fMRI. AB - OBJECTIVE: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor. METHODS: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3T MR scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy. RESULTS: The SNR achieved by daEEG was 11.05+/-3.10 and by OBS was 8.25+/-1.01 (p<0.00001). In 9 of 10 patients, more spikes were detected after daEEG than after OBS (p<0.05). SIGNIFICANCE: daEEG improves signal quality in EEG-fMRI recordings, expanding its clinical and research potential. PMID- 27402598 TI - Multiscale temporal neural dynamics predict performance in a complex sensorimotor task. AB - Ongoing neuronal oscillations are pivotal in brain functioning and are known to influence subjects' performance. This modulation is usually studied on short time scales whilst multiple time scales are rarely considered. In our study we show that Long-Range Temporal Correlations (LRTCs) estimated from the amplitude of EEG oscillations over a range of time-scales predict performance in a complex sensorimotor task, based on Brain-Computer Interfacing (BCI). Our paradigm involved eighty subjects generating covert motor responses to dynamically changing visual cues and thus controlling a computer program through the modulation of neuronal oscillations. The neuronal dynamics were estimated with multichannel EEG. Our results show that: (a) BCI task accuracy may be predicted on the basis of LRTCs measured during the preceding training session, and (b) this result was not due to signal-to-noise ratio of the ongoing neuronal oscillations. Our results provide direct empirical evidence in addition to previous theoretical work suggesting that scale-free neuronal dynamics are important for optimal brain functioning. PMID- 27402599 TI - Neural effects of methylphenidate and nicotine during smooth pursuit eye movements. AB - INTRODUCTION: Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. METHODS: Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). RESULTS: There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DISCUSSION: The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers. PMID- 27402601 TI - The quantification of blood-brain barrier disruption using dynamic contrast enhanced magnetic resonance imaging in aging rhesus monkeys with spontaneous type 2 diabetes mellitus. AB - Microvascular lesions of the body are one of the most serious complications that can affect patients with type 2 diabetes mellitus. The blood-brain barrier (BBB) is a highly selective permeable barrier around the microvessels of the brain. This study investigated BBB disruption in diabetic rhesus monkeys using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Multi-slice DCE-MRI was used to quantify BBB permeability. Five diabetic monkeys and six control monkeys underwent magnetic resonance brain imaging in 3 Tesla MRI system. Regions of the frontal cortex, the temporal cortex, the basal ganglia, the thalamus, and the hippocampus in the two groups were selected as regions of interest to calculate the value of the transport coefficient Ktrans using the extended Tofts model. Permeability in the diabetic monkeys was significantly increased as compared with permeability in the normal control monkeys. Histopathologically, zonula occludens protein-1 decreased, immunoglobulin G leaked out of the blood, and nuclear factor E2-related factor translocated from the cytoplasm to the nuclei. It is likely that diabetes contributed to the increased BBB permeability. PMID- 27402602 TI - Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin. AB - Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine. PMID- 27402600 TI - BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities. AB - Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a "predominantly neurodegenerative" and a "predominantly vascular" cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies. PMID- 27402603 TI - Epigenetic regulation of alternative promoters and enhancers in progenitor, immature, and mature gonadotrope cell lines. AB - Gonadotrope cell identity genes emerge in a stepwise process during mouse pituitary development. Cga, encoding for the alpha-subunit of TSH, LH, and FSH, is initially detected at E11.5 followed by Gnrhr and steroidogenic factor Sf1 at E13.5, specifying cells engaged in a gonadotrope cell fate. Lhb and Fshb appear at E16.5 and 17.5, respectively, typifying differentiated gonadotrope cells. Using the alphaT1-1, alphaT3-1 and LbetaT2 cell lines recapitulating these stages of gonadotrope differentiation, DNA methylation at Gnrhr and Sf1 was investigated. Regulatory regions were found hypermethylated in progenitor alphaT1 1 cells and hypomethylated in differentiated LbetaT2 cells. Abundance of RNA polymerase II together with active histone modifications including H3K4me1, H3K4me3, and H3K27ac were strictly correlated with DNA hypomethylation. Analyses of epigenomic modifications and chromatin accessibility were further extended to Isl1, Lhx3, Gata2, and Pitx2, highlighting alternative usages of specific regulatory gene domains in progenitor alphaT1-1, immature alphaT3-1, and mature LbetaT2 gonadotrope cells. PMID- 27402604 TI - Cervical Myelopathy Doubles the Rate of Dislocation and Fracture After Total Hip Arthroplasty. AB - BACKGROUND: Cervical spondylotic myelopathy (CSM) is a common and underdiagnosed cause of gait dysfunction, rigidity, and falls in the elderly. Given the frequent concurrency of CSM and hip osteoarthritis, this study is designed to evaluate the relative risk of CSM on perioperative and short-term outcomes after total hip arthroplasty (THA). METHODS: The Medicare Standard Analytical Files were searched from 2005 to 2012 to identify all patients undergoing primary THA and the subset of patients with preexisting CSM. Risk ratios with 95% confidence intervals were calculated for 90-day, 1-year, and overall follow-up for common postoperative complications: periprosthetic dislocation, fracture, infection, revision THA, and wound complications. RESULTS: The risk ratios of all surgical complications, including dislocation, periprosthetic fractures, and prosthetic joint infection, were increased approximately 2-fold at all postoperative time points for patients. CONCLUSION: Preexisting CSM is a significant risk factor for primary THA complications including dislocation, periprosthetic fractures, and prosthetic joint infection. PMID- 27402605 TI - Economic Impact of Ketorolac vs Corticosteroid Intra-Articular Knee Injections for Osteoarthritis: A Randomized, Double-Blind, Prospective Study. AB - BACKGROUND: Knee osteoarthritis is a disabling disease that costs billions of dollars to treat. Corticosteroid gives varying pain relief and costs $12 per injection, whereas ketorolac costs $2 per injection, per institutional costs. The aim of this study was to compare ketorolac with corticosteroid based on pain relief using patient outcome measures and cost data. METHODS: A total of 35 patients were randomized to ketorolac or corticosteroid intra-articular knee injection in a double-blind, prospective study. Follow-up was 24 weeks. Osteoarthritis was evaluated using Kellgren-Lawrence grading. Visual analog scale (VAS) was the primary outcome measure. A query of the institutional database was performed for International Classification of Diseases, Ninth Revision codes 715.16 and 719.46, and procedure code 20610 over a 3-year period. Two-way, repeated measures analysis of variance and Spearman rank correlation were used for statistical analysis. RESULTS: Mean VAS for ketorolac and corticosteroid decreased significantly from baseline at 2 weeks, 6.3-4.6 and 5.2-3.6, respectively and remained decreased for 24 weeks. There was no correlation between VAS and demographics within treatments. There were 220, 602, and 405 injections performed on patients with the International Classification of Diseases, Ninth Revision codes 715.16 and 719.46 during 2013, 2014, and 2015, respectively. The cost savings per year using ketorolac instead of corticosteroid would be $2259.40, $6182.54, and $4159.35 for 2013, 2014, and 2015, respectively, with a total savings of $12,601.29 over this period. CONCLUSION: Pain relief was similar between ketorolac and corticosteroid injections. Ketorolac knee injection is safe and effective with a cost savings percentage difference of 143% when compared with corticosteroid. PMID- 27402606 TI - Getting It Right for Patient Safety: Specimen Collection Process Improvement From Operating Room to Pathology. AB - OBJECTIVES: Specimen labeling defects within the perioperative environment are a known patient safety risk that carries the potential for adverse outcomes. These outcomes are a result of errors that occur when unsuspecting providers operate within poorly designed processes with little control over the specimen collection context. Many costly outcomes resulting from labeling errors may include patient harm, inappropriate treatments, lengthy investigations, corrective actions, and, at times, legal action. METHODS: This improvement initiative to identify and reduce the risk of specimen labeling defects includes the application of a disciplined Lean problem-solving approach with the engagement of employees who actually perform the work. RESULTS: By listening to the voice of our internal customers, we collectively redesigned the workflow by collaboratively linking work teams of the operating room and Pathology Department of Henry Ford Hospital, Detroit, over a 2-year period. CONCLUSIONS: We illustrate successful interventions achieved by Lean process management by streamlining, standardizing, and mistake proofing the processes and eliminating waste and inefficiency through systematic problem solving. PMID- 27402607 TI - A Critical Evaluation of the PAXgene Tissue Fixation System: Morphology, Immunohistochemistry, Molecular Biology, and Proteomics. AB - OBJECTIVES: To evaluate the PAXgene tissue fixation system. METHODS: Clinical biospecimens (n = 46) were divided into PAXgene-fixed paraffin-embedded (PFPE), formalin-fixed paraffin-embedded (FFPE), and fresh-frozen (FF) blocks. PFPE and FFPE sections were compared for histology (H&E staining) and immunohistochemistry (14 antibodies) using tissue microarrays. PFPE, FFPE, and FF samples were compared in terms of RNA quality (RNA integrity number, polymerase chain reaction [PCR] amplicon length, and quantitative reverse transcription PCR), DNA quality (gel electrophoresis and methylation profiling) and protein quality (liquid chromatography-mass spectrometry [LC-MS/MS]). RESULTS: PFPE protocol optimization was required in most cases and is described. RNA extracted from PFPE sections was considerably less degraded than that from FFPE sections but more degraded than that from FF blocks. Genomic-length DNA was extracted from PFPE and FF biospecimens, and methylation profiling showed PFPE and FF biospecimens to be almost indistinguishable. Only degraded DNA was extracted from FFPE biospecimens. PFPE sections yielded peptides that were slightly less amenable to LC-MS/MS analysis than FFPE sections, but FF gave slightly better results. CONCLUSIONS: While it cannot be envisaged that PAXgene will replace formalin in a routine clinical setting, for specific projects or immunodiagnostics involving biospecimens destined for immunohistochemical or histologic staining and DNA or RNA analyses, PAXgene is a viable option. PMID- 27402608 TI - Single-Tube 10-Fluorochrome Analysis for Efficient Flow Cytometric Evaluation of Minimal Residual Disease in Plasma Cell Myeloma. AB - OBJECTIVES: Widespread adoption of recent recommendations for minimal residual disease (MRD) detection in myeloma has partly been impeded by a paucity of studies detailing multiparameter flow cytometry (MPF) assay validation. In response, we have validated a novel and efficient single-tube 10-color assay for MRD detection that incorporates the recently recommended plasma cell markers. METHODS: Aspirate samples from 53 patients with plasma cell disorder were analyzed using a novel single-tube 10-color method. The limit of detection, precision of measurement, and linearity of measurement of our new assay were determined using serial dilution experiments. The stability of the new antibody cocktail and the viability/specificity of stained samples were evaluated using serial time course measurements. RESULTS: There was a high degree of quantitative agreement between our new 10-color method and an established eight-color method. Four positive samples detected by the 10-color assay were below or at the limit of detection of the eight-color assay, confirming its high sensitivity. In two cases, subsequent revision of the International Myeloma Working Group Uniform Response Criteria was necessary. CONCLUSION: Adoption of our validated 10-color assay would enable clinical laboratories to satisfy current MRD recommendations without significantly increasing the demands on current workflow practices. PMID- 27402609 TI - Utilization of Chromogenic In Situ Hybridization to Assess Ploidy in the Diagnosis of Hydatidiform Mole. AB - OBJECTIVES: Ploidy assessment is often required for the diagnosis of partial molar pregnancy. While fluorescence in situ hybridization has been shown to be effective, it is not available in many laboratories. We validated chromogenic in situ hybridization (CISH) for this purpose. METHODS: CISH using probes to chromosomes 17 and 10 was performed on 20 POC cases with known cytogenetics to establish a reference percentage. This was then used to classify a randomized set of abnormal and normal cases. RESULTS: An abnormal CISH cutoff of greater than 7% was established. All abnormal cases (six triploid and three tetraploid), 11 "normal" (46, XX or XY or undetectable abnormalities), and one trisomy 10 were all correctly classified by the assay. CONCLUSIONS: CISH is a useful ancillary technique for the diagnosis of molar pregnancy. Its greater accessibility and ability to score even rare placental tissue in a background of maternal tissue offer advantages over other methods. PMID- 27402610 TI - An Examination of the Local Cellular Immune Response to Examples of Both Ductal Carcinoma In Situ (DCIS) of the Breast and DCIS With Microinvasion, With Emphasis on Tertiary Lymphoid Structures and Tumor Infiltrating Lymphoctytes. AB - OBJECTIVES: We tried to describe cellular immune response (tertiary lymphoid structures (TLSs), lymphoid aggregates, tumor infiltrating lymphocytes (TILs)) in neoplastic microenvironment of ductal carcinoma in situ (DCIS) with or without associated microinvasion. METHODS: The histopathologic parameters of 177 DCIS and 27 DCIS with microinvasion were evaluated. We determined number of ducts involved by DCIS, and calculated percentage of these ducts surrounded by TLSs. TILs were quantitated in 27 microinvasive cases. RESULTS: Tumors having higher percentage of DCIS ducts associated with TLSs had higher incidence of microinvasion (P < .001). Percentage of DCIS ducts involved by TLSs was also higher in hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ and TNBC subtypes of DCIS than in HR+/HER2- and HR+/HER2+ subtypes (38.04 +/- 25.8%, 32.6 +/- 32.4%, 2.5 +/- 7.3% and 17.4 +/- 23.3%, respectively, P < .001). In DCIS without microinvasion, HR+/HER2- subtype predominated (P < .001). In microinvasive cases, HR-/HER2+ subtype was most common. TNBC was more common in microinvasive carcinoma than DCIS (P < .001). Among 27 microinvasive ductal carcinomas, increased TLS amount was associated with increased TILs (P = .013). CONCLUSIONS: TLS abundance around DCIS was associated with HER2+ and TNBC subtypes and microinvasion. Pathologists should be aware of microinvasion when diagnosing DCIS lesions with abundant TLSs. PMID- 27402611 TI - Retraction. PMID- 27402612 TI - Implications of Small Samples for Generalization: Adjustments and Rules of Thumb. AB - BACKGROUND: Policy makers and researchers are frequently interested in understanding how effective a particular intervention may be for a specific population. One approach is to assess the degree of similarity between the sample in an experiment and the population. Another approach is to combine information from the experiment and the population to estimate the population average treatment effect (PATE). METHOD: Several methods for assessing the similarity between a sample and population currently exist as well as methods estimating the PATE. In this article, we investigate properties of six of these methods and statistics in the small sample sizes common in education research (i.e., 10-70 sites), evaluating the utility of rules of thumb developed from observational studies in the generalization case. RESULT: In small random samples, large differences between the sample and population can arise simply by chance and many of the statistics commonly used in generalization are a function of both sample size and the number of covariates being compared. The rules of thumb developed in observational studies (which are commonly applied in generalization) are much too conservative given the small sample sizes found in generalization. CONCLUSION: This article implies that sharp inferences to large populations from small experiments are difficult even with probability sampling. Features of random samples should be kept in mind when evaluating the extent to which results from experiments conducted on nonrandom samples might generalize. PMID- 27402613 TI - Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice. AB - The emerging links between breast cancer and metabolic dysfunctions brought forth by the obesity pandemic predict a disproportionate early disease onset in successive generations. Moreover, sensitivity to chemotherapeutic agents may be influenced by the patient's metabolic status that affects the disease outcome. Maternal metabolic stress as a determinant of drug response in progeny is not well defined. Here, we evaluated mammary tumor response to doxorubicin in female mouse mammary tumor virus-Wnt1 transgenic offspring exposed to a metabolically compromised environment imposed by maternal high-fat diet. Control progeny were from dams consuming diets with regular fat content. Maternal high-fat diet exposure increased tumor incidence and reduced tumor latency but did not affect tumor volume response to doxorubicin, compared with control diet exposure. However, doxorubicin-treated tumors from high-fat-diet-exposed offspring demonstrated higher proliferation status (Ki-67), mammary stem cell-associated gene expression (Notch1, Aldh1) and basal stem cell-like (CD29(hi)CD24(+)) epithelial subpopulation frequencies, than tumors from control diet progeny. Notably, all epithelial subpopulations (CD29(hi)CD24(+), CD29(lo)CD24(+), CD29(hi)CD24(+)Thy1(+)) in tumors from high-fat-diet-exposed offspring were refractory to doxorubicin. Further, sera from high-fat-diet-exposed offspring promoted sphere formation of mouse mammary tumor epithelial cells and of human MCF7 cells. Untargeted metabolomics analyses identified higher levels of kynurenine and 2-hydroxyglutarate in plasma of high-fat diet than control diet offspring. Kynurenine/doxorubicin co-treatment of MCF7 cells enhanced the ability to form mammosphere and decreased apoptosis, relative to doxorubicin-only-treated cells. Maternal metabolic dysfunctions during pregnancy and lactation may be targeted to reduce breast cancer risk and improve early drug response in progeny, and may inform clinical management of disease. PMID- 27402614 TI - RET mutation and increased angiogenesis in medullary thyroid carcinomas. AB - Advanced medullary thyroid cancers (MTCs) are now being treated with drugs that inhibit receptor tyrosine kinases, many of which involved in angiogenesis. Response rates vary widely, and toxic effects are common, so treatment should be reserved for MTCs likely to be responsive to these drugs. RET mutations are common in MTCs, but it is unclear how they influence the microvascularization of these tumors. We examined 45 MTCs with germ-line or somatic RET mutations (RETmut group) and 34 with wild-type RET (RETwt). Taqman Low-Density Arrays were used to assess proangiogenic gene expression. Immunohistochemistry was used to assess intratumoral, peritumoral and nontumoral expression levels of VEGFR1, R2, R3, PDGFRa, PDGFB and NOTCH3. We also assessed microvessel density (MVD) and lymphatic vessel density (LVD) based on CD31-positive and podoplanin-positive vessel counts, respectively, and vascular pericyte density based on staining for a-smooth muscle actin (a-SMA), a pericyte marker. Compared with RETwt tumors, RETmut tumors exhibited upregulated expression of proangiogenic genes (mRNA and protein), especially VEGFR1, PDGFB and NOTCH3. MVDs and LVDs were similar in the two groups. However, microvessels in RETmut tumors were more likely to be a-SMA positive, indicating enhanced coverage by pericytes, which play key roles in vessel sprouting, maturation and stabilization. These data suggest that angiogenesis in RETmut MTCs may be more intense and complete than that found in RETwt tumors, a feature that might increase their susceptibility to antiangiogenic therapy. Given their increased vascular pericyte density, RETmut MTCs might also benefit from combined or preliminary treatment with PDGF inhibitors. PMID- 27402615 TI - Transgenic high-lysine rice - a realistic solution to malnutrition? PMID- 27402616 TI - Endogenous auxin biosynthesis and de novo root organogenesis. PMID- 27402617 TI - An examination of the nutritional intake and anthropometric status of individuals with intellectual disabilities: Results from the SOPHIE study. AB - The prevalence of obesity appears greater in people with intellectual disabilities than those in the general population. This study aimed to examine the nutritional intake and anthropometric status of individuals with intellectual disabilities. Participants aged 16-64 years were recruited from intellectual disability service provider organizations ( n = 131). Data were collected using questionnaires; 4-day food dairies and weight, height and waist circumference measurements. Participants' mean body mass index (BMI) was 29.4 kg/m2 +/- 6.1, 2.4% were underweight, 22.6% were normal weight, 28.2% were overweight and 46.8% were obese. Having a diagnosis of Down syndrome ( p = 0.03) was associated with increasing BMI. Increasing waist circumference was associated with increasing severity of ID ( p = 0.04). The mean-reported energy intake was 1890 kcal/day. Mean energy intakes from sugar, fat and saturated fat were above recommendations and few participants met micronutrient recommended daily amounts. This study highlights the alarming prevalence of overweight and obesity and poor diet quality of individuals with intellectual disabilities. PMID- 27402618 TI - Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions. AB - On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. PMID- 27402619 TI - Effect of calorie or exercise labels on menus on calories and macronutrients ordered and calories from specific foods in Hispanic participants: a randomized study. AB - : The effect of menu labels on food choices is unknown in Hispanics. This study evaluated the impact of menu labels on calories and macronutrients ordered in Hispanics. 372 Hispanics (18-65 years) were randomly assigned to menus with no labels (NL) (n=127), rank-ordered calorie labels plus a statement on energy needs per meal (CL) (n=123), or rank-ordered exercise labels showing minutes of brisk walking necessary to burn the food calories (EL) (n=122). The menus had identical food choices. Participants were instructed to select foods from the assigned menu as if having lunch in a fast food restaurant. One-way analysis of variance found no difference in calories ordered (median (25th and 75th centiles)) by menu condition (NL: 785.0 (465.0, 1010.0) kcal; CL: 790.0 (510.0, 1020.0) kcal; EL: 752.5 (520.0, 1033.8) kcal; p=0.75). Calories from specific foods and macronutrient intake were not different by menu condition. Menu label use was 26.8% in the CL and 25.4% in the EL condition. Calories ordered were not different between those who used and those who did not use the labels. Regression analysis showed that perception of being overweight (p=0.02), selecting foods based on health value (p<0.0001), and meeting exercise guidelines (p<0.0001) were associated with fewer calories ordered. Logistic regression showed that selecting foods based on health value (p=0.01) was associated with higher food label use. Menu labels did not affect food choices in Hispanic participants. Future studies should determine if nutrition, exercise, and weight perception counseling prior to menu labels intervention would result in better food choices. TRIAL REGISTRATION NUMBER: NCT02804503; post-results. PMID- 27402620 TI - Calcaneal Z Lengthening Osteotomy Combined With Subtalar Arthroereisis for Severe Adolescent Flexible Flatfoot Reconstruction. AB - BACKGROUND: The timing and strategy for operative treatment of flatfoot are still controversial. The purpose of this study was to evaluate clinical outcomes and radiographic changes following calcaneal Z osteotomy combined with subtalar arthroereisis for severe adolescent flexible flatfoot. METHODS: Data were analyzed for 16 patients (20 feet) who had flatfoot without tibialis posterior tendon dysfunction and were treated by calcaneal Z osteotomy combined with arthroereisis between October 2011 and February 2015. The mean age of patients at the time of surgery was 12.8 +/- 1.4 years (range, 10-14 years). Preoperative and postoperative measurements included changes in hindfoot valgus angles; changes in talonavicular uncoverage angles on anteroposterior (AP) radiographic view; and changes in talo-first metatarsal angles, talar pitch angles, and calcaneal pitch angles on lateral radiographic view. The American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Score (AOFAS-AH) was used to assess foot function. The mean follow-up was 18.9 +/- 6.9 months (range, 13-33 months). RESULTS: The hindfoot valgus angle improved from 14.9 +/- 4.2 degrees to 2.3 +/- 1.7 degrees. On the AP view, the preoperative and postoperative talonavicular uncoverage angles were 30.5 +/- 9.4 degrees and 9.8 +/- 4.8 degrees, respectively. On lateral radiographs, the preoperative talo-first metatarsal angle, talar pitch angle, and calcaneal pitch angle were -22.1 +/- 7.9 degrees, 36.1 +/- 4.4 degrees, and 14.4 +/- 4.0 degrees, respectively. Postoperative lateral radiographs demonstrated talo-first metatarsal angle, talar pitch angle, and calcaneal pitch angle of -6.2 +/- 4.7 degrees, 27.3 +/- 4.9 degrees, and 19.0 +/- 4.3 degrees, respectively. The AOFAS-AH score improved from 66.8 +/- 24.1 preoperatively to 96.5 +/- 3.4 postoperatively. CONCLUSIONS: For adolescents with flatfoot, calcaneal Z osteotomy combined with subtalar arthroereisis provided satisfactory results. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 27402622 TI - Lisdexamfetamine Dimesylate (Vyvanse) for the Treatment of Neurogenic Anejaculation. PMID- 27402623 TI - Concomitant cryoballoon ablation and percutaneous closure of left atrial appendage in patients with atrial fibrillation. AB - AIMS: Pulmonary veins (PVs) isolation is the cornerstone of atrial fibrillation (AF) ablation and can be achieved either by conventional radiofrequency ablation or by cryoenergy. Left atrial appendage (LAA) closure has been proposed as alternative treatment to vitamin K antagonists (VKA). We aimed to evaluate the feasibility of combining cryoballoon (CB) ablation and LAA occlusion in patients with AF and a high thromboembolic risk or contraindication to antithrombotic therapy. METHODS AND RESULTS: Thirty-five patients (28 males, 74 +/- 2 years) underwent CB ablation. Left atrial appendage occlusion was carried out by using two occluder devices (Amplatz Cardiac Plug, ACP, St. Jude Medical, MN, USA, in 25 patients; Watchman, Boston Scientific, MA, USA, in 10 patients). Thirty patients (86%) had previous stroke/TIA episodes, 6 patients (17%) had major bleeding while on VKA therapy, and 7 patients (20%) had inherited bleeding disorders. Over the follow-up (24 +/- 12 months), atrial arrhythmias recurred in 10 (28%) patients. Thirty patients (86%) had complete sealing; 5 patients (14%) showed a residual flow (<5 mm) at first transoesophageal echocardiography (TEE) check, while at 1 year TEE residual flow was detected in 3 patients. In 13 patients (37%), VKA therapy was immediately discontinued. Six patients (17%) received novel oral anticoagulants treatment and then discontinued 3 months thereafter. No device related complications or clinical thromboembolic events occurred. CONCLUSION: Combined CB ablation and LAA closure using different devices appears to be feasible in patients with non-valvular AF associated with high risk of stroke or contraindication to antithrombotic treatment. PMID- 27402621 TI - Type 2 diabetes: genetic data sharing to advance complex disease research. AB - As with other complex diseases, unbiased association studies followed by physiological and experimental characterization have for years formed a paradigm for identifying genes or processes of relevance to type 2 diabetes mellitus (T2D). Recent large-scale common and rare variant genome-wide association studies (GWAS) suggest that substantially larger association studies are needed to identify most T2D loci in the population. To hasten clinical translation of genetic discoveries, new paradigms are also required to aid specialized investigation of nascent hypotheses. We argue for an integrated T2D knowledgebase, designed for a worldwide community to access aggregated large scale genetic data sets, as one paradigm to catalyse convergence of these efforts. PMID- 27402624 TI - EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. PMID- 27402626 TI - Small RNAs Repress Expression of Polysaccharide Utilization Loci of Gut Bacteroides Species. AB - Bacteroides species can metabolize numerous plant polysaccharides and host glycans present in the mammalian gut. The regulatory systems governing the induction of particular polysaccharide utilization loci when the cognate glycan is present are known, but how expression is repressed when a higher-priority glycan is present is largely unknown. In this issue of the Journal of Bacteriology, Cao et al. (J. Bacteriol. 198:2410-2418, 2016, http://dx.doi.org/10.1128/JB.00381-16) reveal a conserved mechanism in Bacteroides whereby antisense small RNAs (sRNA) repress expression of genes involved in utilization of host glycans. PMID- 27402625 TI - Evidence for Escherichia coli Diguanylate Cyclase DgcZ Interlinking Surface Sensing and Adhesion via Multiple Regulatory Routes. AB - DgcZ is the main cyclic dimeric GMP (c-di-GMP)-producing diguanylate cyclase (DGC) controlling biosynthesis of the exopolysaccharide poly-beta-1,6-N acetylglucosamine (poly-GlcNAc or PGA), which is essential for surface attachment of Escherichia coli Although the complex regulation of DgcZ has previously been investigated, its primary role and the physiological conditions under which the protein is active are not fully understood. Transcription of dgcZ is regulated by the two-component system CpxAR activated by the lipoprotein NlpE in response to surface sensing. Here, we show that the negative effect of a cpxR mutation and the positive effect of nlpE overexpression on biofilm formation both depend on DgcZ. Coimmunoprecipitation data suggest several potential interaction partners of DgcZ. Interaction with FrdB, a subunit of the fumarate reductase complex (FRD) involved in anaerobic respiration and in control of flagellum assembly, was further supported by a bacterial-two-hybrid assay. Furthermore, the FRD complex was required for the increase in DgcZ-mediated biofilm formation upon induction of oxidative stress by addition of paraquat. A DgcZ-mVENUS fusion protein was found to localize at one bacterial cell pole in response to alkaline pH and carbon starvation. Based on our data and previous knowledge, an integrative role of DgcZ in regulation of surface attachment is proposed. We speculate that both DgcZ-stimulated PGA biosynthesis and interaction of DgcZ with the FRD complex contribute to impeding bacterial escape from the surface. IMPORTANCE: Bacterial cells can grow by clonal expansion to surface-associated biofilms that are ubiquitous in the environment but also constitute a pervasive problem related to bacterial infections. Cyclic dimeric GMP (c-di-GMP) is a widespread bacterial second messenger involved in regulation of motility and biofilm formation, and plays a primary role in bacterial surface attachment. E. coli possesses a plethora of c-di-GMP-producing diguanylate cyclases, including DgcZ. Our study expands the knowledge on the role of DgcZ in regulation of surface attachment and suggests that it interconnects surface sensing and adhesion via multiple routes. PMID- 27402627 TI - Spermidine Inversely Influences Surface Interactions and Planktonic Growth in Agrobacterium tumefaciens. AB - In bacteria, the functions of polyamines, small linear polycations, are poorly defined, but these metabolites can influence biofilm formation in several systems. Transposon insertions in an ornithine decarboxylase (odc) gene in Agrobacterium tumefaciens, predicted to direct synthesis of the polyamine putrescine from ornithine, resulted in elevated cellulose. Null mutants for odc grew somewhat slowly in a polyamine-free medium but exhibited increased biofilm formation that was dependent on cellulose production. Spermidine is an essential metabolite in A. tumefaciens and is synthesized from putrescine in A. tumefaciens via the stepwise actions of carboxyspermidine dehydrogenase (CASDH) and carboxyspermidine decarboxylase (CASDC). Exogenous addition of either putrescine or spermidine to the odc mutant returned biofilm formation to wild-type levels. Low levels of exogenous spermidine restored growth to CASDH and CASDC mutants, facilitating weak biofilm formation, but this was dampened with increasing concentrations. Norspermidine rescued growth for the odc, CASDH, and CASDC mutants but did not significantly affect their biofilm phenotypes, whereas in the wild type, it stimulated biofilm formation and depressed spermidine levels. The odc mutant produced elevated levels of cyclic diguanylate monophosphate (c-di GMP), exogenous polyamines modulated these levels, and expression of a c-di-GMP phosphodiesterase reversed the enhanced biofilm formation. Prior work revealed accumulation of the precursors putrescine and carboxyspermidine in the CASDH and CASDC mutants, respectively, but unexpectedly, both mutants accumulated homospermidine; here, we show that this requires a homospermidine synthase (hss) homologue. IMPORTANCE: Polyamines are small, positively charged metabolites that are nearly ubiquitous in cellular life. They are often essential in eukaryotes and more variably in bacteria. Polyamines have been reported to influence the surface-attached biofilm formation of several bacteria. In Agrobacterium tumefaciens, mutants with diminished levels of the polyamine spermidine are stimulated for biofilm formation, and exogenous provision of spermidine decreases biofilm formation. Spermidine is also essential for A. tumefaciens growth, but the related polyamine norspermidine exogenously rescues growth and does not diminish biofilm formation, revealing that the growth requirement and biofilm control are separable. Polyamine control of biofilm formation appears to function via effects on the cellular second messenger cyclic diguanylate monophosphate, regulating the transition from a free-living to a surface-attached lifestyle. PMID- 27402629 TI - Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure. AB - BACKGROUND: Takotsubo cardiomyopathy can occur at the early phase of severe acute brain injuries. In the case of cardiac output decrease or shock, the optimal treatment is still a matter of debate. Due to massive stress hormone release, the infusion of catecholamines may have limited effects and may even aggravate cardiac failure. Other inotropic agents may be an option. Levosimendan has been shown to have potential beneficial effects in this setting, although milrinone has not been studied. METHODS: We report a case of a young female presenting with inverted Takotsubo cardiomyopathy syndrome after severe traumatic brain injury. RESULTS: Due to hemodynamic instability and increasing levels of infused norepinephrine, dobutamine infusion was begun but rapidly stopped due to tachyarrhythmia. Milrinone infusion stabilized the patient's hemodynamic status and improved cardiac output without deleterious effects. CONCLUSION: Milrinone could be a good alternative when inotropes are required in Takotsubo cardiomyopathy and when dobutamine infusion is associated with tachyarrhythmia. PMID- 27402628 TI - Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake. AB - Mycobacterium tuberculosis requires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe(3+)-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival of M. tuberculosis, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrophages. But as excess iron is toxic due to its catalytic role in the generation of free radicals, regulation of iron uptake is necessary to maintain optimal levels of intracellular iron. The focus of this review is to present a comprehensive overview of iron homeostasis in M. tuberculosis that is discussed in the context of mycobactin biosynthesis, transport of iron across the mycobacterial cell envelope, and storage of excess iron. The clinical significance of the serum iron status and the expression of the iron-regulated protein HupB in tuberculosis (TB) patients is presented here, highlighting the potential of HupB as a marker, notably in extrapulmonary TB cases. PMID- 27402630 TI - Composition of the epicuticular waxes coating the adaxial side of Phyllostachys aurea leaves: Identification of very-long-chain primary amides. AB - The present study presents comprehensive chemical analyses of cuticular wax mixtures of the bamboo Phyllostachys aurea. The epicuticular and intracuticular waxes were sampled selectively from the adaxial side of leaves on young and old plants and investigated by gas chromatography-mass spectrometry and flame ionization detection. The epi- and intracuticular layers on young and old leaves had wax loads ranging from 1.7 MUg/cm(2) to 1.9 MUg/cm(2). Typical very-long chain aliphatic wax constituents were found with characteristic chain length patterns, including alkyl esters (primarily C48), alkanes (primarily C29), fatty acids (primarily C28 and C16), primary alcohols (primarily C28) and aldehydes (primarily C30). Alicyclic wax components were identified as tocopherols and triterpenoids, including substantial amounts of triterpenoid esters. Alkyl esters, alkanes, fatty acids and aldehydes were found in greater amounts in the epicuticular layer, while primary alcohols and most terpenoids accumulated more in the intracuticular wax. Alkyl esters occurred as mixtures of metamers, combining C20 alcohol with various acids into shorter ester homologs (C36C40), and a wide range of alcohols with C22 and C24 acids into longer esters (C42C52). Primary amides were identified, with a characteristic chain length profile peaking at C30. The amides were present exclusively in the epicuticular layer and thus at or near the surface, where they may affect plant-herbivore or plant pathogen interactions. PMID- 27402631 TI - Computed Tomography Perfusion, Magnetic Resonance Imaging, and Histopathological Findings After Laparoscopic Renal Cryoablation: An In Vivo Pig Model. AB - The present study investigates how computed tomography perfusion scans and magnetic resonance imaging correlates with the histopathological alterations in renal tissue after cryoablation. A total of 15 pigs were subjected to laparoscopic-assisted cryoablation on both kidneys. After intervention, each animal was randomized to a postoperative follow-up period of 1, 2, or 4 weeks, after which computed tomography perfusion and magnetic resonance imaging scans were performed. Immediately after imaging, open bilateral nephrectomy was performed allowing for histopathological examination of the cryolesions. On computed tomography perfusion and magnetic resonance imaging examinations, rim enhancement was observed in the transition zone of the cryolesion 1week after laparoscopic-assisted cryoablation. This rim enhancement was found to subside after 2 and 4 weeks of follow-up, which was consistent with the microscopic examinations revealing of fibrotic scar tissue formation in the peripheral zone of the cryolesion. On T2 magnetic resonance imaging sequences, a thin hypointense rim surrounded the cryolesion, separating it from the adjacent renal parenchyma. Microscopic examinations revealed hemorrhage and later hemosiderin located in the peripheral zone. No nodular or diffuse contrast enhancement was found in the central zone of the cryolesions at any follow-up stage on neither computed tomography perfusion nor magnetic resonance imaging. On microscopic examinations, the central zone was found to consist of coagulative necrosis 1 week after laparoscopic-assisted cryoablation, which was partially replaced by fibrotic scar tissue 4 weeks following laparoscopic-assisted cryoablation. Both computed tomography perfusion and magnetic resonance imaging found the renal collecting system to be involved at all 3 stages of follow-up, but on microscopic examination, the urothelium was found to be intact in all cases. In conclusion, cryoablation effectively destroyed renal parenchyma, leaving the urothelium intact. Both computed tomography perfusion and magnetic resonance imaging reflect the microscopic findings but with some differences, especially regarding the peripheral zone. Magnetic resonance imaging seems an attractive modality for early postoperative follow-up. PMID- 27402633 TI - Weekly Cisplatin and Volumetric-Modulated Arc Therapy With Simultaneous Integrated Boost for Radical Treatment of Advanced Cervical Cancer in Elderly Patients: Feasibility and Clinical Preliminary Results. AB - BACKGROUND: To evaluate the feasibility and clinical preliminary results of weekly cisplatin and volumetric-modulated arc therapy to the pelvis with simultaneous integrated boost to macroscopic disease in a cohort of elderly patients. MATERIALS AND METHODS: Inclusion criteria of this prospective study were age >=70 years, Karnofsky performance status 70 to 100, locally advanced histologically proven squamous cervical carcinoma, and patients unable to undergo brachytherapy. Radiation doses prescribed were 66 Gy to the macroscopic disease and 54 Gy to the pelvic nodes in 30 fractions. Weekly cisplatin dose was 40 mg/mq. RESULTS: A total of 30 patients were recruited. Median follow-up was 32 months (range: 8-48 months). Median age was 72 years (range: 70-84 years). The 3 year overall survival and local control were 93% and 80%, respectively. The median time to progression was 24 months (range: 6-30 months). Analyzing clinical outcome grouping based on the stage of disease, II versus III, the 3-year overall survival was 100% and 85%, respectively. The 3-year local control was 91% for stage II and 67% for stage III. Acute and late toxicities were acceptable without severe events. CONCLUSION: Weekly cisplatin and volumetric-modulated arc therapy simultaneous integrated boost for radical treatment of advanced cervical cancer in the current cohort of elderly patients were feasible. Long-term results and prospective randomized trials are advocated. PMID- 27402632 TI - Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice. AB - BACKGROUND AND OBJECTIVE: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. MATERIALS AND METHODS: The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. RESULTS: The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. CONCLUSION: The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells. PMID- 27402635 TI - Associations between poor living conditions and multi-morbidity among Syrian migrant agricultural workers in Lebanon. AB - BACKGROUND: Syrian migrant farmworkers are among the most marginalized populations in Lebanon, living in poverty, lacking basic legal protections and frequent targets of discrimination. These realities produce living conditions that undermine their basic health and wellbeing. This study explores associations between household living conditions and acute and chronic health problems among Syrian migrant agricultural workers in the Bekaa region of Lebanon. METHODS: A survey was carried out in summer of 2011 with a sample of 290 migrant agriculture workers and members of their household living in a migrant farmworker camp. The survey assessed participants living conditions, assets and health conditions. Regression analyses were carried out to examine associations between multi morbidity and quality of household and neighborhood living conditions. RESULTS: The mean age for the population was 20 years. Forty-seven percent of participants reported health problems. Almost 20% reported either one acute or chronic illness, 15% reported two health problems and 13% reported three or more. The analysis showed a significant positive association between multi-morbidity and poor housing and infrastructure conditions among study participants. CONCLUSION: The situation for migrant communities in Lebanon has likely further deteriorated since the study was conducted, as hundreds of thousands of new migrants have entered Lebanon since the outbreak of the Syrian armed conflict in 2011. These findings should inspire multi-faceted community development initiatives that provide basic minimums of neighborhood infrastructure and housing quality for Syrian migrant informal settlements across Lebanon, safeguarding the health and wellbeing of community residents. PMID- 27402634 TI - Prescription Opioid Misuse Among Rural Community Pharmacy Patients: Pilot Study for Screening and Implications for Future Practice and Research. AB - BACKGROUND: Opioid misuse imposes a disproportionately heavy burden on individuals living in rural areas. Community pharmacy has the potential to expand and coordinate with health professionals to identify and intervene with those who misuse opioids. OBJECTIVE: Rural and urban community pharmacy patients were recruited in this pilot project to describe and compare patterns of opioid misuse. METHODS: We administered a health screening survey in 4 community pharmacies among patients filling opioid medications. Univariate statistics were used to assess differences in health characteristics and opioid medication misuse behaviors between rural and urban respondents. Multivariable statistics were used to identify risk factors associated with rural and urban opioid misuse. RESULTS: A total of 333 participants completed the survey. Participants in rural settings had poorer overall health, higher pain levels, lower education, and a higher rate of unemployment compared to patients in urban pharmacies. Rural respondents with illicit drug use (adjustable odds ratio [aOR]: 14.34, 95% confidence interval [CI] = 2.16-95.38), posttraumatic stress disorder (aOR: 5.44, 95% CI = 1.52 19.50), and <=high school education (aOR: 6.68, 95% CI = 1.06-42.21) had increased risk for opioid misuse. CONCLUSIONS: Community pharmacy represents a promising resource for potential identification of opioid misuse, particularly in rural communities. Continued research must extend these findings and work to establish collaborative services in rural settings. PMID- 27402636 TI - Specific but not Global Cognitive Functions are Associated with Gait Initiation in Older Adults. AB - The objective of this study was to examine the association between cognitive ability and gait initiation performance in older adults. Global and specific cognitive functions and spatiotemporal gait parameters during gait initiation were assessed in 60 older adults. Multivariate linear regression was conducted to determine the association between cognitive functions and gait initiation parameters. Results showed that global cognitive function was not associated with any of the spatiotemporal parameters. Poorer performance on measures of executive function and language ability were associated with shorter step length, narrower step width, and longer step time. In addition, poorer performance on test of visuospatial ability was associated with longer step time. In conclusion, specific but not global cognitive functions were associated with gait initiation performance. Clinical gait examination should incorporate gait initiation and cognitive assessments. Rehabilitation strategies aimed at improving cognition and gait initiation performance may be beneficial for preventing falls. PMID- 27402637 TI - Evaluating Diabetes Educational Interventions With a Skill Development Component in Adolescents With Type 1 Diabetes: A Systematic Review Focusing on Quality of Life. AB - PURPOSE: Adolescents with type 1 diabetes mellitus (T1DM) may have reduced quality of life (QOL) when compared with their peers. This systematic review evaluated the effectiveness of diabetes self-management education (DSME) interventions with a skills development component on the QOL of adolescents with T1DM. METHODS: Six databases were systematically searched for studies on the QOL outcomes of DSME interventions for adolescents with T1DM. Fourteen studies published between 1994 and 2014 met the inclusion criteria. RESULTS: Of the 14 studies, only 4 had significant QOL outcomes for the intervention participants. Successful DSME interventions had indirect behavioral skills foci or a combination of indirect and direct behavioral skills foci and a duration >=2 months. CONCLUSION: This review provides evidence that educational interventions with an indirect behavioral skills development that facilitates diabetes management may improve QOL among adolescents with T1DM. Structured interventions targeting adolescents' QOL are needed to determine which are most effective in improving QOL. Adolescents with T1DM should be routinely screened and monitored for low QOL and referred to QOL-improving interventions. PMID- 27402640 TI - Suboptimal Feeding Practices and High Levels of Undernutrition Among Infants and Young Children in the Rural Communities of Halaba and Zeway, Ethiopia. AB - BACKGROUND: Good nutrition and appropriate child feeding are vital in early stages of child development, particularly in the first 1000 days of life. OBJECTIVE: To assess the adoption of infant and young child feeding practices of World Health Organization, dietary intake, and level of undernutrition in children <2 years of age. METHODS: Baseline cross-sectional study was conducted (January-June 2013) in purposively selected rural communities of Halaba and Zeway, Ethiopia (N = 383 mother-child pairs, randomly selected). RESULTS: Overall prevalence of stunting, wasting, and underweight was 45%, 9%, and 28% in Halaba, and 33%, 7%, and 15% in Zeway, respectively; higher levels of stunting (54% in Halaba and 36% in Zeway) were observed in 6 to 24 months; stunting and underweight, but not wasting, differed by age ( P < .001) in Halaba. Median dietary diversity score in both communities was 2 with 61% to 65% of children consuming 0 to 2 food groupings. Except protein in all age and iron in 12 to 24 months, median intake of energy, iron, zinc, and calcium (and associated nutrient densities) was below the estimated needs that should come from complementary foods in both communities (in subsample). Early initiation of breast-feeding and exclusive breast-feeding was 63% and 86% in Halaba and 92% and 93% in Zeway, respectively ( P < .001). Children receiving minimum acceptable diet were 6% and 9% in Halaba and Zeway, respectively. CONCLUSIONS: The high levels of stunting and suboptimal feeding practices as well as low dietary diversity scores, energy, and nutrient intake in both communities, particularly in Halaba, indicate a need to improve/strengthen nutrition strategies for complementary feeding children in these areas. PMID- 27402638 TI - Renin-angiotensin system blockade for the risk of cancer and death. AB - INTRODUCTION: The effects of renin-angiotensin system blockade with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on cancer remain inconsistent. METHODS: We searched existing databases from 1960 to August 2015, for randomised controlled trials and observational studies (case-control studies and cohort studies) of ARB/ACEI therapy with a minimal one year of follow-up. Outcomes were incidence and mortality of cancer. RESULTS: We included 14 randomised controlled trials and 17 observational studies of 3,957,725 participants (350,329 ARB/ACEI users). The users had a lower incidence of cancer in the observational studies (RR 0.82, 95% CI 0.73-0.93) but not in the randomised controlled trials (RR 1.00, 95% CI 0.92-1.08). The protection persisted for lung cancer (RR 0.85, 95% CI 0.75-0.97) but not for other sites of cancer. The relative risk of cancer associated with renin angiotensin system blockade was reduced along with time of follow-up. Mortality reduction with ARB/ACEI was marginally significant in the observational studies (RR 0.71, 95% CI 0.55-0.93) but not in the randomised controlled trials (RR 0.99, 95% CI 0.89-1.09). CONCLUSIONS: The significant benefits of renin-angiotensin system blockade observed in case-control studies and cohort studies might diminish in randomised controlled trials. Clinical design, site of cancer and duration of follow-up may affect the clinical outcomes. PMID- 27402641 TI - Factors Associated With the Risk of Acute Malnutrition Among Children Aged 6 to 36 Months in Households Targeted by an Emergency Cash Transfer Program. AB - BACKGROUND: Assessing whether and how the expenditure of emergency cash transfer programs (CTPs) relates to child nutritional status is a necessary step for informed program design and targeting. OBJECTIVE: We hypothesized that greater child food expenditures would have a protective effect against the risk of acute malnutrition in the context of a food crisis in Niger. METHODS: We investigated the relationship between food and medical expenditures and acute malnutrition in children aged 6 to 36 months through an observational cohort study of 420 households enrolled in an emergency CTP in Niger. A Cox proportional hazards model was used to estimate the risk of acute malnutrition while adjusting for relevant child and household characteristics. RESULTS: Seventy-four (18% of the cohort) children developed acute malnutrition. The risk was 1.79 times higher among ill children than healthy children (hazard ratio [HR]: 1.79; 95% confidence interval [CI]: 1.10-2.92; P < .05), nearly 3 times higher among children in the poorest households than those in wealthier households (HR: 2.98; 95% CI: 1.86 4.78; P < .001), and 2.85 times lower with each unit increase in baseline weight for-height Z score (HR: 0.35; 95% CI: 0.23-0.53; P < .001). Food expenditures were not associated with risk (HR: 0.97; 95% CI: 0.87-1.07; P > .05). CONCLUSION: Our findings highlight the importance of the health-related determinants of child undernutrition and suggest that a potential role of emergency CTPs may be to enable and promote health service access where services exist. They also indicate a need for more sustained poverty reduction and undernutrition prevention activities in concert with well-timed and strategic use of emergency interventions. PMID- 27402639 TI - Comparison of blood pressure measurements on the bare arm, over a sleeve and over a rolled-up sleeve in the elderly. AB - BACKGROUND: Although guidelines recommend that blood pressure (BP) should be measured on a bare arm, BP is sometimes measured over clothing in clinical settings. OBJECTIVE: To assess the accuracy of BP measurements over clothing rolled up to the elbow in clinical settings. METHODS: This was a cross-sectional study to a total of 186 individuals recruited from a primary care clinic and two day-care facilities between July and September 2014. Main outcome measures were BP measurements on (i) a bare arm, (ii) over the sleeve of a cardigan and (iii) over the sleeve of a cardigan rolled up to the elbow. BP was compared across measurement conditions using the paired t-test and multiple analysis of variance adjusting for age, sex, measurement order and interaction between clothing condition and measurement order. RESULTS: Of 186 subjects, 38.5% were male. Mean age was 74.6 years. Mean BP with a bare arm, over a sleeve and over a rolled-up sleeve was 128.9 (SD 19.1)/67.4 (10.8) mmHg, 132.8 (21.0)/72.6 (11.5) mmHg and 133.4 (21.3)/74.4 (12.1) mmHg, respectively. There were significant differences in BP between the bare arm and over a cardigan sleeve (P < 0.001) and the bare arm and over a rolled-up cardigan sleeve (P < 0.001). BP differences were significant even after adjusting for age group, sex, measurement order and interaction between clothing condition and measurement order. CONCLUSIONS: Although previous studies have suggested BP measurements over clothing are acceptable, our results suggest that BP should be measured on bare arms as recommended by guidelines whenever feasible. PMID- 27402642 TI - Correlation of Body Mass Index and Physical Activity Among 7- to 11-Year Children at Zahedan, Iran. AB - BACKGROUND: Childhood obesity is currently one of the major concerns in pediatric field. In recent literature, correlation of obesity with some behavioral factors such as physical activity (PA) received attention. OBJECTIVE: The purpose of this study was to determine the relationship between body mass index (BMI) and PA. MATERIALS AND METHODS: This cross-sectional study was carried out in 2012 on 548 randomly selected 7- to 11-year schoolchildren from Zahedan, Iran. The underweight, normal weight, overweight, and obesity status were all based on BMI percentiles for age and sex. Moderate to vigorous PA during the previous 7 days was assessed by a modified version of the Physical Activity Questionnaire for Children. RESULTS: The prevalence of underweight, normal weight, overweight, and obesity among the participants was 18.3%, 47.9%, 11.8%, and 22.1%, respectively. Overweight and obesity were significantly higher among girls than boys. Mean PA score in participants was 2.4 +/- 0.5. The results showed the PA score was significantly higher among boys than girls. The PA score had a significant association with BMI ( P = .018), and it was greater in normal participants than in obese participants. CONCLUSION: On the basis of observed data and due to the impact of PA on BMI as an indicator of nutritional status and health, teaching children to have better nutrition and lifestyle changes is very important. Therefore, more studies should focus on childhood obesity prevention programs to prevent nonoverweight children from becoming overweight or obese in the future. PMID- 27402643 TI - Suicide and murder-suicide involving automobiles. AB - OBJECTIVE: We aim to explore the phenomenon of suicide by driving one vehicle into another, and draw attention to the cost to occupants of targeted vehicles. METHOD: We examined academic literature, court and newspaper reports, and online sources. RESULTS: Driver suicide may be achieved by colliding with a fixed object or another vehicle. When a second vehicle is targeted, the occupants of that vehicle experience property loss, and potentially physical and psychiatric injury, or death. Driver suicides are associated with death of another person, in 11.3% of cases. Some suicidal individuals are able to act with great consideration for the consequences of their actions. CONCLUSION: Every effort must be made to help suicidal people with mental disorders or other predicaments. There is a need for public discussion of suicide by targeting an oncoming vehicle. It is less likely that suicide drivers who target other vehicles are unable to choose and more likely they have not considered the consequences of their actions. PMID- 27402645 TI - A letter from CMAJ's Editorial Advisory Board. PMID- 27402646 TI - CMA Board of Directors responds. PMID- 27402647 TI - Lyme Disease guidelines. PMID- 27402648 TI - Prevention better than harm reduction. PMID- 27402649 TI - Resting heart rate and wearable technology. PMID- 27402650 TI - Prevalence and clinical aspects of tungiasis in south-west Nigerian schoolchildren. AB - Tungiasis is highly prevalent in resource-poor communities in sub-Saharan Africa, but studies among schoolchildren are scanty. We assessed prevalence, parasite load and clinical aspects of tungiasis in schoolchildren in south-western Nigeria. A total of 545 schoolchildren was examined. Of these, 133 (24.4%; 95% CI, 20.9-28.2%) were infested with Tunga penetrans Boys showed a higher prevalence than girls (31% versus 18%, P < 0.0001); in those infested, the median number of lesions was two, with no gender difference (2 boys, interquartile range, 1-4; 2 girls; interquartile range, 1-4; P = 0.34). The maximum number of 44 lesions was found in a 14-year-old boy. Desquamation was present in 90.2%, followed by erythema (54.9%) and oedema (43.6%); 54.9% showed any chronic pathology and more one-third nail deformations. Our study indicates that tungiasis is an important health problem in rural Nigerian schoolchildren. Sustainable interventions are required to control the disease in this and similar communities. PMID- 27402651 TI - Correction: Painful knees and hearing-loss: a rare presentation of meningococcal disease. PMID- 27402652 TI - Uterine incarceration in a primigravid retroverted bicornuate uterus. AB - Uterine incarceration is a rare complication that usually occurs after the first trimester of pregnancy. It leads to increased maternal and/or fetal morbidity and mortality. Risk factors include retroversion of uterus and other pelvic abnormalities. Clinical presentation includes severe abdominal and pelvic pain symptoms. Patients can present with concurrent urinary symptoms due to increasing distortion of adjacent structures from the enlarging uterus. A high clinical suspicion of uterine incarceration is confirmed with ultrasound. More advanced imaging such as MRI can be used as an adjunct to ultrasound imaging. Progression from expectant management to intervention is recommended as soon as possible to prevent complications such as uterine rupture and fetal demise. In subsequent pregnancies, close monitoring with serial ultrasounds is warranted to monitor for recurrence of incarceration which has been reported in a few rare cases. PMID- 27402653 TI - Left atrial myxoma complicated by acute embolism to the left subclavian artery. PMID- 27402654 TI - Treatment of opioid use disorder in an innovative community-based setting after multiple treatment attempts in a woman with untreated HIV. AB - Opioid use disorder is associated with significant health and social harms. Various evidence-based interventions have proven successful in mitigating these harms, including harm reduction strategies and pharmacological treatment such as methadone. We present a case of a 35-year-old HIV-positive woman who was off antiretroviral therapy due to untreated opioid use disorder, and had a history of frequently self-discharging from hospital against medical advice. During the most recent hospital admission, the patient was transferred to an innovative community based clinical support residence that supported harm reduction. Initially, she received methadone to only manage the withdrawal symptoms rather than for long term maintenance therapy. However, with gradual dose increases to treat cravings and withdrawal, she ultimately discontinued all drug use and reinitiated antiretroviral therapy. This case highlights that patients whose goal is not abstinence can be successfully treated for acute medical illnesses and comorbid substance use disorders using harm reduction approaches, including appropriate dosing of pharmacotherapy. PMID- 27402655 TI - In vivo early retinal structural alterations following laser photocoagulation using three-dimensional spectral domain optical coherence tomography. AB - To study the retinal structural alterations and surface topography of retinal pigment epithelium (RPE) immediately following laser photocoagulation up to day 7. Cross-sectional retinal imaging and RPE segmentation maps on spectral domain optical coherence tomography were obtained immediately at hour 1, day 1, day 4 and day 7 following 532 nm neodymium:YAG laser photocoagulation in a 56-year-old male patient for branch retinal vein occlusion. Immediately postlaser, loss of reflectivity of all the retinal layers was observed. At hour 1, hyper reflectivity of outer retinal layers was observed with increase in hyporeflective spaces by day 1. Immediately postlaser, pitting of the RPE was observed on surface topography which regressed at day 1. On day 4, smooth RPE surface topography was observed with the occurrence of small elevated areas on day 7. The present report provides an insight into the in vivo changes in the retinal structure and RPE surface topography after laser photocoagulation. PMID- 27402656 TI - Birth brachial plexus palsy: a race against time. AB - A 5-year-old child presented to us with weakness of the left upper limb since birth. With the given history of obstetric trauma and limb examination, a diagnosis of birth brachial plexus palsy was made. Brachial plexus exploration along with microsurgery was performed at the same time which included extrinsic neurolysis of the roots and trunks and nerve transfer for better shoulder external rotation and elbow flexion. Both the movements were severely restricted previously due to co-contractures with the shoulder internal rotators and triceps. The problem of birth brachial plexus palsy is proving to be a global health burden both in developed countries and in developing countries such as India. The lack of awareness among the general public and primary healthcare providers and inadequate orthopaedic and neurosurgeons trained to treat the condition have worsened the prognosis. This case lays stress on the delayed complications in birth brachial palsy and its effective management. PMID- 27402657 TI - Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment. AB - This case report describes a female patient diagnosed with Barraquer-Simons syndrome, a rare form of acquired partial lipodystrophy characterised by symmetrical loss of adipose tissue from face, neck, upper extremities and the trunk with onset in early childhood. Initial symptoms were seen at the age of 8 years. Our patient did not show signs of renal impairment and this may be associated with the syndrome. Treatment of lipoatrophy in these patients is limited to cosmetic restoration, and autologous fat grafting has shown sustained positive effects with no or very little loss of volume at follow-ups. Furthermore, the treatment has resulted in considerable improvements in her quality of life and daily functioning. She has not experienced any adverse effects. Accurate and early diagnosis is important, and clinicians should consider early intervention for these patients. Autologous fat grafting is recommended as a safe procedure. PMID- 27402658 TI - Universal Scale of Intelligence Estimates (USIE): Representing Intelligence Estimated From Level of Education. AB - In clinical neuropsychology, it is often necessary to estimate a patient's premorbid level of cognitive functioning in order to evaluate whether his scores on cognitive tests should be considered abnormal. In practice, test results from before the onset of brain pathology are rarely available, and the patient's level of education is used instead as an estimate of his premorbid level. Unfortunately, level of education may be expressed on many different scales of education, which are difficult to use interchangeably. Here, we introduce a new scale that has the capacity to replace existing scales and can be used interchangeably with any of them: the Universal Scale of Intelligence Estimates (USIE). To achieve this, we propose to map all levels of existing educational scales to standard IQ scores. This USIE point estimate is supplemented with an estimation interval. We assert that USIE offers some important benefits for clinical practice and research. PMID- 27402659 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27402660 TI - Short- and Long-Term Effects of Concurrent Strength and HIIT Training in Octogenarians with COPD. AB - To investigate the short- and long-term effects of concurrent strength and high intensity interval training (HIIT) on octogenarian COPD patients, nine males (age = 84.2 +/- 2.8 years, BMI = 29.3 +/- 2.3) with low to severe COPD levels (2.1 +/- 1.5 BODE index) underwent a supervised 9-week strength and HIIT exercise program. Training had a significant (p < .05) impact on senior fitness test scores (23 45%), 30-m walking speed (from 1.29 +/- 0.29-1.62 +/- 0.33 m/s), leg and chest press 1RM (38% and 45% respectively), maximal isometric strength (30-35%), and 6 min walking test (from 286.1 +/- 107.2-396.2 +/- 106.5 m), and tended to increase predicted forced vital capacity by 14% (p = .07). One year after the intervention all training-induced gains returned to their preintervention values except for the chest press 1RM (p <.05). Short-term concurrent strength and HIIT training increases physical fitness in the oldest-old COPD patients, and has potential long-term benefits. PMID- 27402661 TI - Relationship of Phenylthiocarbamide (PTC) Taster Status to Olfactory and Gustatory Function in Patients with Chemosensory Disturbances. AB - Poor sensitivity to the bitter taste of phenylthiocarbamide (PTC) and related substances has been associated with a number of diseases. We determined, in patients with chemosensory dysfunction from multiple etiologies, whether PTC "tasters" (n = 511) exhibit less smell and taste dysfunction than their non-PTC tasting counterparts (n = 432) on a comprehensive battery of olfactory and gustatory tests. The proportion of tasters (54%) in our study population was much lower than that calculated from 11 North American population studies (76.5%; P < 0.0001). This taster/nontaster ratio was maintained across a range of etiologic categories. More women (60.7%) than men (45.5%) were PTC tasters (P < 0.0001). Although PTC tasting status was unrelated to scores on the olfactory tests (which included tests of odor identification, detection threshold, and odor memory/discrimination), tasters significantly outperformed nontasters on suprathreshold identification and intensity taste tests employing both bitter (caffeine) and nonbitter (sucrose, citric acid, sodium chloride) tasting stimuli. Regardless of PTC taster status, women outperformed men on the taste tests. Our findings suggest the possibility that the T2R38 gene may protect against significant olfactory dysfunction, but once such dysfunction becomes manifest at a level where professional help is sought, such protection is not evident. However, other hypotheses for this phenomenon are possible. This study demonstrates that patients with chemosensory disturbances who are PTC tasters outperform their non-PTC taster counterparts in both identifying and perceiving the intensity of a range of suprathreshold tastants, including ones that do not taste bitter. PMID- 27402662 TI - Interventions Aimed at Reducing Use of Low-Value Health Services: A Systematic Review. AB - The effectiveness of different types of interventions to reduce low-value care has been insufficiently summarized to allow for translation to practice. This article systematically reviews the literature on the effectiveness of interventions to reduce low-value care and the quality of those studies. We found that multicomponent interventions addressing both patient and clinician roles in overuse have the greatest potential to reduce low-value care. Clinical decision support and performance feedback are promising strategies with a solid evidence base, and provider education yields changes by itself and when paired with other strategies. Further research is needed on the effectiveness of pay-for performance, insurer restrictions, and risk-sharing contracts to reduce use of low-value care. While the literature reveals important evidence on strategies used to reduce low-value care, meaningful gaps persist. More experimentation, paired with rigorous evaluation and publication, is needed. PMID- 27402663 TI - Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography. AB - The anatomy of the adult human left ventricle (LV) is the result of its complex interaction with its environment. From the fetal to the neonatal to the adult form, the human LV undergoes an anatomical transformation that finally results in the most complex of the four cardiac chambers. In its adult form, the human LV consists of two muscular helixes that surround the midventricular circumferential layer of muscle fibers. Contraction of these endocardial and epicardial helixes results in a twisting motion that is thought to minimize the transmural stress of the LV muscle. In the healthy myocardium, the LV twist response to stimuli that alter preload, afterload, or contractility has been described and is deemed relatively consistent and predictable. Conversely, the LV twist response in patient populations appears to be a little more variable and less predictable, yet it has revealed important insight into the effect of cardiovascular disease on LV mechanical function. This review discusses important methodological aspects of assessing LV twist and evaluates the LV twist responses to the main physiological and pathophysiological states. It is concluded that correct assessment of LV twist mechanics holds significant potential to advance our understanding of LV function in human health and cardiovascular disease. PMID- 27402664 TI - Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model. AB - Serelaxin, recombinant human relaxin-2, modulates endothelial vasodilatory functionality and is under evaluation for treatment of acute heart failure. Little is known about acute effects on cerebral perfusion. We tested the hypothesis that Serelaxin might also have effects on the cerebral microcirculation in a sheep model, which resembles human brain structure quite well. We used laser Doppler flowmetry and sidestream dark-field (SDF) imaging techniques, which are reliable tools to continuously assess dynamic changes in cerebral perfusion. Laser Doppler flowmetry shows that bolus injection of 30 MUg Serelaxin/kg body wt induces an increase (P = 0.006) to roughly 150% of cortical cerebral blood flow (CBF), whereas subcortical CBF remains unchanged (P = 0.688). The effects on area-dependent CBF were significantly different after the bolus injection (P = 0.042). Effects on cortical CBF were further confirmed by SDF imaging. The bolus injection of Serelaxin increased total vessel density to 127% (P = 0.00046), perfused vessel density to 145% (P = 0.024), and perfused capillary density to 153% (P = 0.024). Western blotting confirmed the expression of relaxin receptors RXFP1 and truncated RXFP2-variants in the respective brain regions, suggesting a possible contribution of RXFP1 on the effects of Serelaxin. In conclusion, the injection of a high dose of Serelaxin exerts quick effects on the cerebral microcirculation. Therefore, Serelaxin might be suitable to improve cortical microcirculation and exert neuroprotective effects in clinically relevant scenarios that involve cortical hypoperfusion. These findings need to be confirmed in relevant experimental settings involving cerebral cortical hypoperfusion and can possibly be translated into clinical practice. PMID- 27402665 TI - Impact of coronary bifurcation morphology on wave propagation. AB - The branching pattern of the coronary vasculature is a key determinant of its function and plays a crucial role in shaping the pressure and velocity wave forms measured for clinical diagnosis. However, although multiple scaling laws have been proposed to characterize the branching pattern, the implications they have on wave propagation remain unassessed to date. To bridge this gap, we have developed a new theoretical framework by combining the mathematical formulation of scaling laws with the wave propagation theory in the pulsatile flow regime. This framework was then validated in multiple species using high-resolution cryomicrotome images of porcine, canine, and human coronary networks. Results demonstrate that the forward well-matchedness (no reflection for pressure/flow waves traveling from the coronary stem toward the microcirculation) is a salient feature in the coronary vasculature, and this result remains robust under many scenarios of the underlying pulse wave speed distribution assumed in the network. This result also implies a significant damping of the backward traveling waves, especially for smaller vessels (radius, <0.3 mm). Furthermore, the theoretical prediction of increasing area ratios (ratio between the area of the mother and daughter vessels) in more symmetric bifurcations found in the distal circulation was confirmed by experimental measurements. No differences were observed by clustering the vessel segments in terms of transmurality (from epicardium to endocardium) or perfusion territories (left anterior descending, left circumflex, and right coronary artery). PMID- 27402667 TI - Intermittent hypoxia and arterial blood pressure control in humans: role of the peripheral vasculature and carotid baroreflex. AB - Intermittent hypoxia (IH) occurs in association with obstructive sleep apnea and likely contributes to the pathogenesis of hypertension. The purpose of this study was to examine the putative early adaptations at the level of the peripheral vasculature and carotid baroreflex (CBR) that may promote the development of hypertension. Ten healthy male participants (26 +/- 1 yr, BMI = 24 +/- 1 kg/m(2)) were exposed to 6 h of IH (1-min cycles of normoxia and hypoxia) and SHAM in a single-blinded, counterbalanced crossover study design. Ambulatory blood pressure was measured during each condition and the following night. Vascular strain of the carotid and femoral artery, a measure of localized arterial stiffness, and hemodynamic shear patterns in the brachial and femoral arteries were measured during each condition. Brachial artery reactive hyperemia flow-mediated vasodilation was assessed before and after each condition as a measure of endothelial function. CBR function and its control over leg vascular conductance (LVC) were measured after each condition with a variable-pressure neck chamber. Intermittent hypoxia 1) increased nighttime pulse pressure by 3.2 +/- 1.3 mmHg, 2) altered femoral but not brachial artery hemodynamics, 3) did not affect brachial artery endothelial function, 4) reduced vascular strain in the carotid and possibly femoral artery, and 5) shifted CBR mean arterial pressure (MAP) to higher MAP while blunting LVC responses to CBR loading. These results suggest limb-specific vascular impairments, reduced vascular strain, and CBR resetting combined with blunted LVC responses are factors in the early pathogenesis of IH induced development of hypertension. PMID- 27402666 TI - Stimulation of the hypothalamic arcuate nucleus increases brown adipose tissue nerve activity via hypothalamic paraventricular and dorsomedial nuclei. AB - Hypothalamic arcuate nucleus (ARCN) stimulation elicited increases in sympathetic nerve activity (IBATSNA) and temperature (TBAT) of interscapular brown adipose tissue (IBAT). The role of hypothalamic dorsomedial (DMN) and paraventricular (PVN) nuclei in mediating these responses was studied in urethane-anesthetized, artificially ventilated, male Wistar rats. In different groups of rats, inhibition of neurons in the DMN and PVN by microinjections of muscimol attenuated the increases in IBATSNA and TBAT elicited by microinjections of N methyl-d-aspartic acid into the ipsilateral ARCN. In other groups of rats, blockade of ionotropic glutamate receptors by combined microinjections of D(-)-2 amino-7-phosphono-heptanoic acid (D-AP7) and NBQX into the DMN and PVN attenuated increases in IBATSNA and TBAT elicited by ARCN stimulation. Blockade of melanocortin 3/4 receptors in the DMN and PVN in other groups of rats resulted in attenuation of increases in IBATSNA and TBAT elicited by ipsilateral ARCN stimulation. Microinjections of Fluoro-Gold into the DMN resulted in retrograde labeling of cells in the ipsilateral ARCN, and some of these cells contained proopiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha-MSH), or vesicular glutamate transporter-3. Since similar projections from ARCN to the PVN have been reported by us and others, these results indicate that neurons containing POMC, alpha-MSH, and glutamate project from the ARCN to the DMN and PVN. Stimulation of ARCN results in the release of alpha-MSH and glutamate in the DMN and PVN which, in turn, cause increases in IBATSNA and TBAT. PMID- 27402668 TI - Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension. AB - Salt-induced hypertension leads to development of left ventricular hypertrophy in the Dahl salt-sensitive (Dahl/SS) rat. Before progression to left ventricular failure, the heart initially undergoes a compensated hypertrophic response. We hypothesized that changes in myocardial energetics may be an early indicator of transition to failure. Dahl/SS rats and their salt-resistant consomic controls (SS-13(BN)) were placed on either a low- or high-salt diet to generate four cohorts: Dahl-SS rats on a low- (Dahl-LS) or high-salt diet (Dahl-HS), and SS 13(BN) rats on a low- (SSBN-LS) or high-salt diet (SSBN-HS). We isolated left ventricular trabeculae and characterized their mechanoenergetic performance. Our results show, at most, modest effects of salt-induced compensated hypertrophy on myocardial energetics. We found that the Dahl-HS cohort had a higher work-loop heat of activation (estimated from the intercept of the heat vs. relative afterload relationship generated from work-loop contractions) relative to the SSBN-HS cohort and a higher economy of contraction (inverse of the slope of the heat vs. active stress relation) relative to the Dahl-LS cohort. The maximum extent of shortening and maximum shortening velocity of the Dahl/SS groups were higher than those of the SS-13(BN) groups. Despite these differences, no significant effect of salt-induced hypertension was observed for either peak work output or peak mechanical efficiency during compensated hypertrophy. PMID- 27402669 TI - CaMKII-dependent phosphorylation regulates basal cardiac pacemaker function via modulation of local Ca2+ releases. AB - Spontaneous beating of the heart pacemaker, the sinoatrial node, is generated by sinoatrial node cells (SANC) due to gradual change of the membrane potential called diastolic depolarization (DD). Spontaneous, submembrane local Ca(2+) releases (LCR) from ryanodine receptors (RyR) occur during late DD and activate an inward Na(+)/Ca(2+)exchange current to boost the DD rate and fire an action potential (AP). Here we studied the extent of basal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation and the role of basal CaMKII-dependent protein phosphorylation in generation of LCRs and regulation of normal automaticity of intact rabbit SANC. The basal level of activated (autophosphorylated) CaMKII in rabbit SANC surpassed that in ventricular myocytes (VM) by approximately twofold, and this was accompanied by high basal level of protein phosphorylation. Specifically, phosphorylation of phospholamban (PLB) at the CaMKII-dependent Thr(17) site was approximately threefold greater in SANC compared with VM, and RyR phosphorylation at CaMKII-dependent Ser(2815) site was ~10-fold greater in the SA node, compared with that in ventricle. CaMKII inhibition reduced phosphorylation of PLB and RyR, decreased LCR size, increased LCR periods (time from AP-induced Ca(2+) transient to subsequent LCR), and suppressed spontaneous SANC firing. Graded changes in CaMKII-dependent phosphorylation (indexed by PLB phosphorylation at the Thr(17)site) produced by CaMKII inhibition, beta-AR stimulation or phosphodiesterase inhibition were highly correlated with changes in SR Ca(2+) replenishment times and LCR periods and concomitant changes in spontaneous SANC cycle lengths (R(2) = 0.96). Thus high basal CaMKII activation modifies the phosphorylation state of Ca(2+) cycling proteins PLB, RyR, L-type Ca(2+) channels (and likely others), adjusting LCR period and characteristics, and ultimately regulates both normal and reserve cardiac pacemaker function. PMID- 27402671 TI - HPLC Enantioseparation of beta-Blockers on Ovomucoid Stationary Phase. AB - The purpose of this study was to separate single and multiple pairs of six beta blockers enantiomers by high performance liquid chromatography on ovomucoid (OM) column in optimal conditions. The separation was performed isocratically or in gradient elution at 25 degrees C, flow rate of 1 mL/min and 220 nm. The mobile phase consisted of phosphate buffer/acetonitrile or methanol. The effect of the organic modifier, the influence of pH and the percentage of the aqueous phase on resolution were investigated. The elution order of propranolol (PRP) enantiomers was established as well as the detection and quantification limits. The results show that OM was suitable for enantiomeric separation of the nonselective beta blockers carvedilol, PRP, pindolol and oxprenolol, and not for the two beta-1 selective blockers, atenolol and metoprolol. A hypothesis regarding a possible correlation between structure-pharmacological activity-chromatographic behavior is proposed. PMID- 27402670 TI - Structure and hemodynamics of vascular networks in the chorioallantoic membrane of the chicken. AB - The chick chorioallantoic membrane (CAM) is extensively used as an in vivo model. Here, structure and hemodynamics of CAM vessel trees were analyzed and compared with predictions of Murray's law. CAM microvascular networks of Hamburger Hamilton stage 40 chick embryos were scanned by videomicroscopy. Three networks with ~3,800, 580, and 480 segments were digitally reconstructed, neglecting the capillary mesh. Vessel diameters (D) and segment lengths were measured, and generation numbers and junctional exponents at bifurcations were derived. In selected vessels, flow velocities (v) and hematocrit were measured. Hemodynamic simulations, incorporating the branching of capillaries from preterminal vessels, were used to estimate v, volume flow, shear stress (tau), and pressure for all segments of the largest network. For individual arteriovenous flow pathways, terminal arterial and venous generation numbers are negatively correlated, leading to low variability of total topological and morphological pathway lengths. Arteriolar velocity is proportional to diameter (v?D1.03 measured, v?D0.93 modeling), giving nearly uniform tau levels (tau?D0.05). Venular trees exhibit slightly higher exponents (v?D1.3, tau?D0.38). Junctional exponents at divergent and convergent bifurcations were 2.05 +/- 1.13 and 1.97 +/- 0.95 (mean +/- SD) in contrast to the value 3 predicted by Murray's law. In accordance with Murray's law, tau levels are (nearly) maintained in CAM arterial (venular) trees, suggesting vascular adaptation to shear stress. Arterial and venous trees show an interdigitating arrangement providing homogeneous flow pathway properties and have preterminal capillary branches. These properties may facilitate efficient oxygen exchange in the CAM during rapid embryonic growth. PMID- 27402672 TI - Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans. AB - The placenta richly expresses nonheme and heme Fe transport proteins. To address the impact of maternal and neonatal Fe status and hepcidin on the regulation of these proteins, mRNA expression and protein abundance of nonheme and heme Fe transport proteins were evaluated in placental tissue from 154 adolescents. Regression analyses found maternal Fe status was significantly associated with multiple placental nonheme and heme transporters, whereas neonatal Fe status was related to only 3 heme transporters. Across statistical analyses, maternal Fe status was consistently associated with the placental nonheme Fe importer transferrin receptor 1 (TfR1). Protein abundance of TfR1 was related to midgestation maternal serum ferritin (SF) (beta = -0.32; P = 0.005) and serum TfR (beta = 0.25; P = 0.024). Protein abundance of the heme importer, proton-coupled folate transporter, was related to neonatal SF (beta = 0.30; P = 0.016) and serum TfR (beta = -0.46; P < 0.0001). Neonatal SF was also related to mRNA expression of the heme exporter feline leukemia virus subgroup C receptor 1 (beta = -0.30; P = 0.004). In summary, maternal Fe insufficiency during pregnancy predicts increased expression of the placental nonheme Fe transporter TfR1. Associations between placental heme Fe transporters and neonatal Fe status require further study.-Best, C. M., Pressman, E. K., Cao, C., Cooper, E., Guillet, R., Yost, O. L., Galati, J., Kent, T. R., O'Brien, K. O. Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans. PMID- 27402673 TI - Transcriptional activation and translocation of ancient NOS during immune response. AB - NOS is the key component of the NO system, which plays an indispensable role in many physiologic and immunologic processes; however, the process that underlies the activation of ancient NOSs and their functions remains unclear. Expression of Crassostrea gigas NOS (CgNOS) mRNA in hemocytes was examined after stimulating oysters with LPS and TNF-alpha. Expression level of CgNOS mRNA was increased significantly, by 2.61-fold (P < 0.05), at 24 h poststimulation. A positive CgNOS signal was detected via immunoprecipitation, and only one protein was detected in oyster hemocytes. Shifting and supershifting bands were observed in EMSAs between the CgNOS promoter and the transcription factors CgNF-kappaB1 and Cg-signal transducer and activator of transcription (STAT). CgNF-kappaB1 was detected in the nucleus only at 12 h, whereas CgSTAT was observed in the cytoplasm and nucleus at 12 and 24 h. Expression levels of tyrosine-protein kinase receptor Tie 1, phosphatidylinositide phosphatase SAC2, phosphatidylinositol-4-phosphate 5 kinase type-1alpha, diacylglycerol kinase theta, LPS-induced TNF-alpha factor like protein, cAMP-dependent transcription factor-2, NF-kappaB1, and STAT6 were significantly elevated in a transcriptome analysis after 12 h of LPS and TNF alpha stimulation. An immunoreactive CgNOS signal was observed in both the cell membrane and cytoplasm at 12 h, whereas it was mainly localized to the cytoplasm at 24 h post-LPS and -TNF-alpha stimulation. These findings revealed that CgNOS could be transcriptionally activated by CgNF-kappaB1 and CgSTAT via the PI3K-Akt pathway, similar to what occurs for iNOS, but CgNOS translocated to the cytoplasm, similar to neuronal NOS, to modulate downstream signals during an immune defense. These results collectively provide crucial knowledge about the evolution of NOS structure and function.-Jiang, Q., Liu, Z., Zhou, Z., Wang, L., Wang, L., Yue, F., Wang, J., Wang, H., Song, L. Transcriptional activation and translocation of ancient NOS during immune response. PMID- 27402674 TI - Novel role for p56/Lck in regulation of endothelial cell survival and angiogenesis. AB - Previous studies have demonstrated that cleaved high-molecular-weight kininogen (HKa) induces endothelial apoptosis and inhibits angiogenesis and have suggested that this occurs through inhibition of Src family kinases. This study assessed the role of tyrosine-protein kinase Lck (p56/Lck) in this pathway. We analyzed early events leading to apoptosis of human endothelial cells exposed to HKa. The role of p56/Lck was investigated using short interfering (si) RNA knockdown and lentivirus expression in assays of endothelial tube formation, sprouting of neovessels from murine aorta, and angiogenesis in Matrigel plugs. HKa stimulated expression and phosphorylation of p56/Lck. siRNA knockdown of p56/Lck promoted endothelial proliferation and blocked HKa-induced apoptosis and activation of p53, Bax, and Bak. Lentivirus expression of p56/Lck in endothelial cells induced apoptosis and blocked tube formation. Expression of p56/Lck in murine aortic rings blocked sprouting angiogenesis. Lentivirus expressing p56/Lck blocked angiogenesis in Matrigel plugs, while p56/Lck short hairpin RNA inhibited the antiangiogenic effect of HKa. Scrambled siRNAs and empty lentiviral vectors were used in all experiments. Apoptosis of proliferating endothelial cells and inhibition of angiogenesis by HKa requires p56/Lck. This suggests a novel role for p56/Lck in regulation of endothelial cell survival and angiogenesis. Betapudi, V., Shukla, M., Alluri, R., Merkulov, S., McCrae, K. R. Novel role for p56/Lck in regulation of endothelial cell survival and angiogenesis. PMID- 27402675 TI - Mitochondrial adaptations to high-volume exercise training are rapidly reversed after a reduction in training volume in human skeletal muscle. AB - Increased mitochondrial content and respiration have both been reported after exercise training. However, no study has directly compared how different training volumes influence mitochondrial respiration and markers of mitochondrial biogenesis. Ten healthy men performed high-intensity interval cycling during 3 consecutive training phases; 4 wk of normal-volume training (NVT; 3/wk), followed by 20 d of high-volume training (HVT; 2/d) and 2 wk of reduced-volume training (RVT; 5 sessions). Resting biopsy samples (vastus lateralis) were obtained at baseline and after each phase. No mitochondrial parameter changed after NVT. After HVT, mitochondrial respiration and citrate synthase activity (~40-50%), as well as the protein content of electron transport system (ETS) subunits (~10 40%), and that of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), NRF1, mitochondrial transcription factor A (TFAM), PHF20, and p53 (~65-170%) all increased compared to baseline; mitochondrial specific respiration remained unchanged. After RVT, all the mitochondrial parameters measured except citrate synthase activity (~36% above initial) were not significantly different compared to baseline (all P > 0.05). Our findings demonstrate that training volume is an important determinant of training-induced mitochondrial adaptations and highlight the rapid reversibility of human skeletal muscle to a reduction in training volume.-Granata, C., Oliveira, R. S. F., Little, J. P., Renner, K., Bishop, D. J. Mitochondrial adaptations to high-volume exercise training are rapidly reversed after a reduction in training volume in human skeletal muscle. PMID- 27402676 TI - Increasing the Energy Expenditure of Seated Activities in Older Adults with a Portable Elliptical Device. AB - BACKGROUND: The ill-health effects of sedentary behavior are becoming well documented, yet older adults spend 70-80% of waking hours sedentary. PURPOSE: To determine if a portable elliptical device increases energy expenditure (EE) while performing popular seated activities. METHODS: Twenty older adults (68.1 +/- 1.4 years) participated to compare the measured EE between seated rest and three randomized seated pedaling activities: computer use, reading, TV viewing. Each pedaling activity included 5-min of self-selected paced/no resistance (SSP) and externally paced/added resistance pedaling (Paced). RESULTS: A significant increase in EE existed during SSP (+1.44 +/- 0.12 kcal/min) and Paced (+2.19 +/- 0.09 kcal/min) pedaling relative to Seated Rest (p < .001). EE during the Paced activities was significantly greater than all SSP activities (p <.01). CONCLUSION: Extrapolating these results, pedaling at a SSP for an hour while performing seated activities is equivalent to the net EE of walking 1.6 miles. Future home-based effectiveness and feasibility should be explored. PMID- 27402677 TI - BioCreative V track 4: a shared task for the extraction of causal network information using the Biological Expression Language. AB - Automatic extraction of biological network information is one of the most desired and most complex tasks in biological and medical text mining. Track 4 at BioCreative V attempts to approach this complexity using fragments of large-scale manually curated biological networks, represented in Biological Expression Language (BEL), as training and test data. BEL is an advanced knowledge representation format which has been designed to be both human readable and machine processable. The specific goal of track 4 was to evaluate text mining systems capable of automatically constructing BEL statements from given evidence text, and of retrieving evidence text for given BEL statements. Given the complexity of the task, we designed an evaluation methodology which gives credit to partially correct statements. We identified various levels of information expressed by BEL statements, such as entities, functions, relations, and introduced an evaluation framework which rewards systems capable of delivering useful BEL fragments at each of these levels. The aim of this evaluation method is to help identify the characteristics of the systems which, if combined, would be most useful for achieving the overall goal of automatically constructing causal biological networks from text. PMID- 27402678 TI - TMC-SNPdb: an Indian germline variant database derived from whole exome sequences. AB - Cancer is predominantly a somatic disease. A mutant allele present in a cancer cell genome is considered somatic when it's absent in the paired normal genome along with public SNP databases. The current build of dbSNP, the most comprehensive public SNP database, however inadequately represents several non European Caucasian populations, posing a limitation in cancer genomic analyses of data from these populations. We present the T: ata M: emorial C: entre-SNP D: ata B: ase (TMC-SNPdb), as the first open source, flexible, upgradable, and freely available SNP database (accessible through dbSNP build 149 and ANNOVAR) representing 114 309 unique germline variants-generated from whole exome data of 62 normal samples derived from cancer patients of Indian origin. The TMC-SNPdb is presented with a companion subtraction tool that can be executed with command line option or using an easy-to-use graphical user interface with the ability to deplete additional Indian population specific SNPs over and above dbSNP and 1000 Genomes databases. Using an institutional generated whole exome data set of 132 samples of Indian origin, we demonstrate that TMC-SNPdb could deplete 42, 33 and 28% false positive somatic events post dbSNP depletion in Indian origin tongue, gallbladder, and cervical cancer samples, respectively. Beyond cancer somatic analyses, we anticipate utility of the TMC-SNPdb in several Mendelian germline diseases. In addition to dbSNP build 149 and ANNOVAR, the TMC-SNPdb along with the subtraction tool is available for download in the public domain at the following:Database URL: http://www.actrec.gov.in/pi webpages/AmitDutt/TMCSNP/TMCSNPdp.html. PMID- 27402679 TI - FANTOM5 transcriptome catalog of cellular states based on Semantic MediaWiki. AB - The Functional Annotation of the Mammalian Genome project (FANTOM5) mapped transcription start sites (TSSs) and measured their activities in a diverse range of biological samples. The FANTOM5 project generated a large data set; including detailed information about the profiled samples, the uncovered TSSs at high base pair resolution on the genome, their transcriptional initiation activities, and further information of transcriptional regulation. Data sets to explore transcriptome in individual cellular states encoded in the mammalian genomes have been enriched by a series of additional analysis, based on the raw experimental data, along with the progress of the research activities. To make the heterogeneous data set accessible and useful for investigators, we developed a web-based database called Semantic catalog of Samples, Transcription initiation And Regulators (SSTAR). SSTAR utilizes the open source wiki software MediaWiki along with the Semantic MediaWiki (SMW) extension, which provides flexibility to model, store, and display a series of data sets produced during the course of the FANTOM5 project. Our use of SMW demonstrates the utility of the framework for dissemination of large-scale analysis results. SSTAR is a case study in handling biological data generated from a large-scale research project in terms of maintenance and growth alongside research activities.Database URL: http://fantom.gsc.riken.jp/5/sstar/. PMID- 27402680 TI - The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans. AB - This study was designed to determine the levels of prolactin, leptin, osteopontin, and follistatin in workers chronically and subacutely exposed to lead compounds. The examined population consisted of three groups. The first group was composed of 56 male workers who were chronically exposed to lead for 13.38 +/- 10.38 years. The second group served as a control group and consisted of 24 male administrative workers, while the third group included 32 male workers exposed to lead for 40 +/- 3 days. The levels of leptin, osteopontin, and prolactin were significantly lower in the group of workers chronically exposed to lead than in the control group by 42%, 26%, and 41%, respectively. The levels of follistatin did not differ between those groups. The levels of all measured hormones did not change after a short-term exposure to lead compared to baseline. Chronic lead exposure is associated with significantly decreased level of prolactin, leptin, and osteopontin. Lead-induced changes in the levels of these hormones may disturb many functions of the human body, including the immune response, metabolism, reproduction, and bone turnover. PMID- 27402681 TI - The apoptotic effects of silibinin on MDA-MB-231 and MCF-7 human breast carcinoma cells. AB - BACKGROUND: Silibinin is a bioactive flavonolignan extracted from milk thistle, known as Silybum marianum. Silibinin exerts strong antiproliferative, proapoptotic, and anti-inflammatory effects. Many studies have shown that silibinin inhibits experimentally induced malignancies of the liver, prostate, skin, and colon as well as promotes inhibition of the proliferation of cancer cell lines in vitro. This study aimed to investigate the effects of silibinin on the human breast carcinoma cell lines MDA-MB-231 and MCF-7 in monolayer and spheroid cultures. METHOD: The MDA-MB-231 and MCF-7 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with silibinin at 24, 48, and 72 h of incubation. The 5-bromo-2'-deoxyuridine labeling index was used to determine the cells of the synthesis phase. Poly-ADP-ribose-polimerase immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick and labeling assay were used to determine the death of cells in both the monolayer and spheroid cultures. RESULTS: An half maximal inhibitory concentration dose of silibinin in MDA-MB-231 and MCF-7 cells was 100 uM/mL at 24, 48, and 72 h of incubation. Terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase were detected after treatment with silibinin in both the monolayer and spheroid cultures. The dead cell count was higher in the MDA-MB-231 and MCF-7 cell lines with silibinin applied than in the controls. CONCLUSIONS: Our study demonstrated that silibinin applications enhanced terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase in comparison to the control in both the monolayer and spheroid cultures. PMID- 27402682 TI - Comparative evaluation of ceftriaxone- and cefotaxime-induced biliary pseudolithiasis or nephrolithiasis: A prospective study in 154 children. AB - BACKGROUND: Biliary lithiasis, or sludge, and nephrolithiasis have been reported as a possible complication of ceftriaxone therapy. However, no study related to cefotaxime-induced biliary pseudolithiasis or nephrolithiasis was observed in the literature. Therefore, we investigated the comparative formation of biliary pseudolithiasis and nephrolithiasis after cefotaxime and ceftriaxone therapies. METHODS: The patients treated with ceftriaxone or cefotaxime were enrolled during the study period. Ultrasound imaging of the biliary and urinary tract was performed in all patients before and after the treatment. The patients with a positive sonographic finding at the end of treatment were followed up with monthly ultrasonography for 3 months. RESULTS: The present study showed that abnormal biliary sonographic findings were demonstrated in 18 children (20.9%) treated with ceftriaxone, 13 (15.1%) had biliary lithiasis, 5 (5.8%) had biliary sludge and 1 (1.2%) had nephrolithiasis. Abnormal biliary sonographic findings were demonstrated in only four (5.9%) children treated with cefotaxime who had biliary sludge and only one (1.5%) had nephrolithiasis. It was observed that older age was at significantly higher risk of developing biliary sludge or stone formation. Receiver operating characteristic analysis was performed to determine the residual risk and analysis found that 4.5 years was the cut-off value for age. CONCLUSIONS: The present study is unique in the literature for reporting for the first time gall bladder sludge and nephrolithiasis associated with cefotaxime use. Therefore, patients treated with cefotaxime should be monitored for serious complications like patients treated with ceftriaxone. Nevertheless, if third generation cephalosporin is used, cefotaxime is recommended to be used rather than ceftriaxone. PMID- 27402683 TI - The effect of acute ophiobolin A treatment on HO-mediated inflammatory processes. AB - Many microbial and plant-derived metabolites contribute to the production of inflammatory mediators and the expression of pro-inflammatory molecules. Ophiobolin A (OPA) is a fungal secondary metabolite produced by Bipolaris species. The aim of our study was to examine the acute effects of this compound on inflammatory processes. Male Wistar rats were treated with 5% ethanol, 0.01 mg/kg OPA, 0.1 mg/kg OPA and 1.0 mg/kg OPA per os. After 24 h of the administrations, inflammatory mediators such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO) enzyme as well as heme oxygenase (HO) activity were measured in both plasma and cardiac tissue, along with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We found that OPA caused a significant elevation in the concentrations of IL-6 and TNF-alpha, increased MPO activity and decreased HO enzyme activity in the plasma. While OPA induces inflammation in the plasma, it did not change the level of inflammatory mediators in the cardiac tissue and the concentrations of serum ALT and AST. Our findings indicate that rapid release of inflammatory mediators by OPA promotes systemic inflammation. However, this acute OPA treatment does not show toxic effects on the cardiac tissue and the concentrations of liver enzymes. PMID- 27402684 TI - Rest-Activity Patterns in Older Adults with Heart Failure and Healthy Older Adults. AB - The purpose of this investigation is to examine differences in rest-activity patterns and sleep characteristics in older adults with heart failure (HF) and healthy older adults. The sample included older adults with HF (n = 20) and a reference group of healthy older adults (n = 20). Traditional cosinor analysis was used to assess three parameters of rest-activity from wrist actigraphy data: amplitude (range of activity), mesor (mean activity), and acrophase (time of peak activity). Traditional sleep characteristics were also determined from actigraphy data: total sleep time (TST), sleep latency (SL), sleep efficiency (SE), and wake after sleep onset (WASO). The HF group demonstrated significantly lower mesor and amplitude than the reference group (p < .01). The HF group had significantly greater TST (p < .01), but the groups had similar SE, SL, and WASO. Despite similar sleep characteristics to healthy older adults, overall rest-activity patterns were significantly dampened in those with HF. PMID- 27402685 TI - Tunable Diode Laser Absorption Spectroscopy Sensor for Calibration Free Humidity Measurements in Pure Methane and Low CO2 Natural Gas. AB - We report a new direct tunable diode laser absorption spectroscopy (dTDLAS) sensor for absolute measurements of H2O in methane, ethane, propane, and low CO2 natural gas. The sensor is operated with a 2.7 um DFB laser, equipped with a high pressure single pass gas cell, and used to measure H2O amount of substance fractions in the range of 0.31-25 000 umol/mol. Operating total gas pressures are up to 5000 hPa. The sensor has been characterized, addressing the traceability of the spectrometric results to the SI and the evaluation of the combined uncertainty, following the guide to the expression of uncertainty in measurement (GUM). The relative reproducibility of H2O amount of substance fraction measurements at 87 umol/mol is 0.26% (0.23 umol/mol). The maximum precision of the sensor was determined using a H2O in methane mixture, and found to be 40 nmol/mol for a time resolution of 100 s. This corresponds to a normalized detection limit of 330 nmol mol-1.m Hz-1/2. The relative combined uncertainty of H2O amount fraction measurements delivered by the sensor is 1.2%. PMID- 27402686 TI - Optimal Experimental Condition of IR pMAIRS Calibrated by Using an Optically Isotropic Thin Film Exhibiting the Berreman Effect. AB - Infrared (IR) p-polarized multiple-angle incidence resolution spectrometry (pMAIRS) is a useful spectroscopic tool for revealing the molecular anisotropic structure in a thin film, which is used for the molecular orientation analysis of many functionalized organic thin films. Infrared pMAIRS provides both in-plane (IP) and out-of-plane (OP) vibrational mode spectra, which are influenced by the choice of the angles of incidence, i.e., angle set. To obtain quantitatively reliable pMAIRS spectra, therefore, the optimal angle set must be revealed. In a former study, an optimization study was carried out on a silicon substrate by using the band intensity ratio of the IP and OP spectra of highly oriented molecules in a thin film, which has a problem that the optimized results cannot be used for another substrate. In the present study, a totally new idea using an optically isotropic thin film as a standard sample is proposed to comprehensively explore the optimal angle set on various substrates: the band shift due to the Berreman effect of a strongly absorbing compound is used, instead of the band intensity. This new approach makes the pMAIRS calibration for various substrates a much easier task. With the optimal angle set, the molecular orientation angle in the film calculated by the pMAIRS spectra is also found to be reliable quantitatively. This technique opens a user-friendly way to a reliable molecular orientation analysis in an ultrathin film using IR pMAIRS. PMID- 27402687 TI - Algorithmic Enhancement of Spectral Resolution of a LiNbO3 Waveguide-Based Miniature Fourier Transform Spectrometer. AB - In a recent report we demonstrated a miniature static Fourier transform spectrometer (FTS) that was implemented with a LiNbO3 (LN) waveguide electro optic modulator (EOM) combined with the dispersion relation between its half-wave voltage and wavelength. The FTS was verified to be able to measure laser wavelength and for low-resolution spectroscopy. In this report, we successfully applied the resolution enhancement algorithm to the FTS, resulting in at least a three-fold increase in its spectral resolution without causing obvious distortion of the measured spectra. The algorithm method used is based on an autoregressive (AR) model, singular value decomposition (SVD), and forward-backward linear prediction (FBLP). The combination of these methods allows the FTS to remain a small size but to possess good spectral resolution, effectively mitigating the conflict between the small size and high resolution of the device. This study opens the way to development of high-resolution miniature FTS. PMID- 27402688 TI - Laser-induced Fluorescence Spectroscopy (LIFS) for Discrimination of Genetically Close Sweet Orange Accessions ( Citrus sinensis L. Osbeck). AB - Although there is substantial diversity among cultivated sweet oranges genotypes with respect to morphological, physiological, and agronomic traits, very little variation at DNA level has been observed. It is possible that this low DNA molecular variability is due to a narrow genetic basis commonly observed in this citrus group. The most different morphological characters observed were originated through mutations, which are maintained by vegetative propagation. Despite all molecular tools available for discrimination between these different accessions, in general, low polymorphism has been observed in all groups of sweet oranges and they may not be identified by molecular markers. In this context, this paper describes the results obtained by using laser-induced fluorescent spectroscopy (LIFS) as a tool to discriminate sweet orange accessions ( Citrus sinensis L. Osbeck) including common, low acidity, pigmented, and navel orange groups, with very little variation at DNA level. The findings showed that LIFS combined with statistical methods is capable to discriminate different accessions. The basic idea is that citrus leaves have multiple fluorophores and concentration depends on their genetics and metabolism. Thus, we consider that the optical properties of citrus leaves may be different, depending on variety. The results have shown that the developed method, for the best classification rate, reaches an average sensitivity and specificity of 95% and 97.5%, respectively. An interesting application of this study is the development of an economically viable tool for early identification in seedling certification, in citrus breeding programs, in cultivar protection, or in germplasm core collection. PMID- 27402689 TI - Objective Assessment of Adherence to Global Recommendations on Physical Activity for Health in Relation to Spirometric Values in Nonsmoker Women Aged 60-75 Years. AB - The purpose of this study was to determine the strength of the relationship between forced expiratory spirometric tests and physical activity levels in older women divided into two groups based on whether they met or did not meet guidelines for weekly physical activity according to the Global Recommendations on Physical Activity for Health (WHO, 2011). Research included 61 healthy, nonsmoker female seniors (Mage = 66 years, SDage = 4.4 years). Weekly physical activity was assessed using an ActiGraph GT3X triaxial accelerometer. To evaluate pulmonary function, forced spirometry tests were performed. The women who met criteria of physical activity for health achieved significantly higher values for forced vital capacity (FVC), t(59) = -1.58, p < .001, and forced expiratory volume in 1 s (FEV1), t(59) = -3.33, p = .002. Meeting criteria of Global Recommendations on Physical Activity for Health is associated with better FVC and FEV1 parameters in healthy older women. PMID- 27402691 TI - Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770. AB - Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX 770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients. PMID- 27402693 TI - PetriScape - A plugin for discrete Petri net simulations in Cytoscape. AB - Systems biology plays a central role for biological network analysis in the post genomic era. Cytoscape is the standard bioinformatics tool offering the community an extensible platform for computational analysis of the emerging cellular network together with experimental omics data sets. However, only few apps/plugins/tools are available for simulating network dynamics in Cytoscape 3. Many approaches of varying complexity exist but none of them have been integrated into Cytoscape as app/plugin yet. Here, we introduce PetriScape, the first Petri net simulator for Cytoscape. Although discrete Petri nets are quite simplistic models, they are capable of modeling global network properties and simulating their behaviour. In addition, they are easily understood and well visualizable. PetriScape comes with the following main functionalities: (1) import of biological networks in SBML format, (2) conversion into a Petri net, (3) visualization as Petri net, and (4) simulation and visualization of the token flow in Cytoscape. PetriScape is the first Cytoscape plugin for Petri nets. It allows a straightforward Petri net model creation, simulation and visualization with Cytoscape, providing clues about the activity of key components in biological networks. PMID- 27402692 TI - GABAA- and glycine-mediated inhibitory modulation of the cough reflex in the caudal nucleus tractus solitarii of the rabbit. AB - Cough-related sensory inputs from rapidly adapting receptors (RARs) and C fibers are processed by second-order neurons mainly located in the caudal nucleus tractus solitarii (NTS). Both GABAA and glycine receptors have been proven to be involved in the inhibitory control of second-order cells receiving RAR projections. We investigated the role of these receptors within the caudal NTS in the modulation of the cough reflex induced by either mechanical or chemical stimulation of the tracheobronchial tree in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nl) of the receptor antagonists bicuculline and strychnine as well as of the receptor agonists muscimol and glycine were performed. Bicuculline (0.1 mM) and strychnine (1 mM) caused decreases in peak abdominal activity and marked increases in respiratory frequency due to decreases in both inspiratory time (Ti) and expiratory time (Te), without concomitant changes in arterial blood pressure. Noticeably, these microinjections induced potentiation of the cough reflex consisting of increases in the cough number associated with decreases either in cough-related Ti after bicuculline or in both cough-related Ti and Te after strychnine. The effects caused by muscimol (0.1 mM) and glycine (10 mM) were in the opposite direction to those produced by the corresponding antagonists. The results show that both GABAA and glycine receptors within the caudal NTS mediate a potent inhibitory modulation of the pattern of breathing and cough reflex responses. They strongly suggest that disinhibition is one important mechanism underlying cough regulation and possibly provide new hints for novel effective antitussive strategies. PMID- 27402690 TI - Differential regulation of autophagy and mitophagy in pulmonary diseases. AB - Lysosomal-mediated degradation of intracellular lipids, proteins and organelles, known as autophagy, represents a inducible adaptive response to lung injury resulting from exposure to insults, such as hypoxia, microbes, inflammation, ischemia-reperfusion, pharmaceuticals (e.g., bleomycin), or inhaled xenobiotics (i.e., air pollution, cigarette smoke). This process clears damaged or toxic cellular constituents and facilitates cell survival in stressful environments. Autophagic degradation of dysfunctional or damaged mitochondria is termed mitophagy. Enhanced mitophagy is usually an early response to promote survival. However, overwhelming or prolonged mitochondrial damage can induce excessive/pathological levels of mitophagy, thereby promoting cell death and tissue injury. Autophagy/mitophagy is therefore an important modulator in human pulmonary diseases and a potential therapeutic target. This review article will summarize the most recent studies highlighting the role of autophagy/mitophagy and its molecular pathways involved in stress response in pulmonary pathologies. PMID- 27402694 TI - Determinants of VH1-46 Cross-Reactivity to Pemphigus Vulgaris Autoantigen Desmoglein 3 and Rotavirus Antigen VP6. AB - Shared VH1-46 gene usage has been described in B cells reacting to desmoglein 3 (Dsg3) in the autoimmune disease pemphigus vulgaris (PV), as well as B cells responding to rotavirus capsid protein VP6. In both diseases, VH1-46 B cells bearing few to no somatic mutations can recognize the disease Ag. This intriguing connection between an autoimmune response to self-antigen and an immune response to foreign Ag prompted us to investigate whether VH1-46 B cells may be predisposed to Dsg3-VP6 cross-reactivity. Focused testing of VH1-46 mAbs previously isolated from PV and rotavirus-exposed individuals indicates that cross-reactivity is rare, found in only one of seven VH1-46 IgG clonotypes. High throughput screening of IgG B cell repertoires from two PV patients identified no additional cross-reactive clonotypes. Screening of IgM B cell repertoires from one non-PV and three PV patients identified specific cross-reactive Abs in one PV patient, but notably all six cross-reactive clonotypes used VH1-46. Site-directed mutagenesis studies indicate that amino acid residues predisposing VH1-46 Abs to Dsg3 reactivity reside in CDR2. However, somatic mutations only rarely promote Dsg3-VP6 cross-reactivity; most mutations abolish VP6 and/or Dsg3 reactivity. Nevertheless, functional testing identified two cross-reactive VH1-46 Abs that both disrupt keratinocyte adhesion and inhibit rotavirus replication, indicating the potential for VH1-46 Abs to have both pathologic autoimmune and protective immune functions. Taken together, these studies suggest that certain VH1-46 B cell populations may be predisposed to Dsg3-VP6 cross-reactivity, but multiple mechanisms prevent the onset of autoimmunity after rotavirus exposure. PMID- 27402695 TI - Impact of Staphylococcus aureus USA300 Colonization and Skin Infections on Systemic Immune Responses in Humans. AB - Staphylococcus aureus is both a commensal and a pathogen, and USA300, a strain that is usually methicillin-resistant but can sometimes be methicillin susceptible, has been causing skin and soft tissue infections (SSTIs) in epidemic proportions among otherwise healthy individuals. Although many people are colonized with S. aureus strains, including some with USA300, few of these colonized individuals develop SSTIs. This prompts the hypothesis that infections may develop in individuals with somewhat reduced innate and/or adaptive immune responses to S. aureus, either because prior S. aureus colonization has dampened such responses selectively, or because of more globally reduced immune reactivity. In this study, we analyzed the S. aureus colonization status and PBMC responses to innate and adaptive stimuli in 72 patients with SSTIs and 143 uninfected demographically matched controls. Contrary to the hypothesis formulated, PBMCs from infected patients obtained at the time of infection displayed enhanced innate cytokine production upon restimulation compared with PBMCs from controls, a difference that disappeared after infection resolution. Notably, PBMCs from patients infected with a documented USA300 SSTI displayed greater innate cytokine production than did those from patients infected with documented non-USA300 genotypes. Moreover, colonization with USA300 in infected patients, regardless of their infecting strain, correlated with increased production of IL-10, IL-17A, and IL-22 compared with patients colonized with non USA300 subtypes. Thus, our results demonstrate that infected patients associated with USA300 either as an infecting strain, or as a colonizing strain, have systemic immune responses of greater magnitude than do those associated with other S. aureus subtypes. PMID- 27402696 TI - A Novel mTORC1-Dependent, Akt-Independent Pathway Differentiates the Gut Tropism of Regulatory and Conventional CD4 T Cells. AB - The vitamin A metabolite all-trans retinoic acid (ATRA) induces a gut-homing phenotype in activated CD4(+) conventional T cells (Tconv) by upregulating the integrin alpha4beta7 and the chemokine receptor CCR9. We report that, in contrast to mouse Tconv, only ~50% of regulatory T cells (Treg) upregulate CCR9 when stimulated by physiological levels of ATRA, even though Tconv and Treg express similar levels of the retinoic acid receptor (RAR). The resulting bimodal CCR9 expression is not associated with differences in the extent of their proliferation, level of Foxp3 expression, or affiliation with naturally occurring Treg or induced Treg in the circulating Treg pool. Furthermore, we find that exposure of Treg to the mechanistic target of rapamycin (mTOR) inhibitor rapamycin suppresses upregulation of both CCR9 and alpha4beta7, an effect that is not evident with Tconv. This suggests that in Treg, ATRA-induced upregulation of CCR9 and alpha4beta7 is dependent on activation of a mTOR signaling pathway. The involvement of mTOR is independent of Akt activity, because specific inhibition of Akt, pyruvate dehydrogenase kinase-1, or its downstream target glycogen synthase kinase-3 did not prevent CCR9 expression. Additionally, Rictor (mTOR complex [mTORC]2)-deficient Treg showed unaltered ability to express CCR9, whereas Raptor (mTORC1)-deficient Treg were unable to upregulate CCR9, suggesting the selective participation of mTORC1. These findings reveal a novel difference between ATRA signaling and chemokine receptor induction in Treg versus Tconv and provide a framework via which the migratory behavior of Treg versus Tconv might be regulated differentially for therapeutic purposes. PMID- 27402697 TI - Identification of Evolutionarily Conserved Md1 Splice Variants That Regulate Innate Immunity through Differential Induction of NF-kB. AB - Although in mammals the TLR4/myeloid differentiation factor (MD)2/CD14 complex is responsible for the recognition of bacterial LPS, and it is known that the RP105/MD1 complex negatively regulates TLR4 signaling, the evolutionary history of LPS recognition remains enigmatic. Thus, zebrafish has orthologs of mammalian TLR4 (Tlr4a and Tlr4b), RP105, and MD1, but MD2 and CD14 seem to be absent from all fish genomes available to date. In addition, and to make the story more intriguing, zebrafish Tlr4a and Tlr4b do not recognize LPS, whereas the zebrafish Rp105/Md1 complex unexpectedly participates in the regulation of innate immunity and viral resistance. In this work, we report the identification of two novel splice variants of Md1, which are expressed at similar levels as full-length Md1 in the main immune-related organs of zebrafish and are highly induced upon viral infection. One of these splice variants, which is also expressed by mouse macrophages, lacks three conserved cysteine residues that have been shown to form disulfide bonds that are crucial for the three-dimensional structure of the MD-2 related lipid recognition domain of Md1. Functional studies in zebrafish demonstrate that this evolutionarily conserved splice variant shows higher antiviral activity than full-length Md1, but reduced proinflammatory activity, due to an impaired ability to activate the master regulator of inflammation, NF kappaB. These results uncover a previously unappreciated evolutionarily conserved Md1 splice variant with important functions in the regulation of innate immunity and the antiviral response in zebrafish, and point to the need for additional functional studies in mammals on this little explored molecule. PMID- 27402698 TI - Mucosal Langerhans Cells Promote Differentiation of Th17 Cells in a Murine Model of Periodontitis but Are Not Required for Porphyromonas gingivalis-Driven Alveolar Bone Destruction. AB - Periodontitis is a chronic oral inflammatory disease affecting one in five individuals that can lead to tooth loss. CD4(+) Th cells activated by a microbial biofilm are thought to contribute to the destruction of alveolar bone surrounding teeth by influencing osteoclastogenesis through IL-17A and receptor activator for NF-kappaB ligand effects. The relative roles of mucosal Ag presentation cells in directing Th cell immune responses against oral pathogens and their contribution to destruction of alveolar bone remain unknown. We tested the contribution of mucosal Langerhans cells (LCs) to alveolar bone homeostasis in mice following oral colonization with a well-characterized human periodontal pathogen, Porphyromonas gingivalis We found that oral mucosal LCs did not protect from or exacerbate crestal alveolar bone destruction but were responsible for promoting differentiation of Th17 cells specific to P. gingivalis. In mice lacking LCs the Th17 response was suppressed and a Th1 response predominated. Bypassing LCs with systemic immunization of P. gingivalis resulted in a predominantly P. gingivalis specific Th1 response regardless of whether LCs were present. Interestingly, we find that in vivo clonal expansion of P. gingivalis-specific Th cells and induced regulatory T cells does not depend on mucosal LCs. Furthermore, destruction of crestal alveolar bone induced by P. gingivalis colonization occurred regardless of the presence of mucosal LCs or P. gingivalis-specific Th17 cells. Our data indicate that both LCs and Th17 cells are redundant in contributing to alveolar bone destruction in a murine model of periodontitis. PMID- 27402699 TI - Dual Inhibition of Rip2 and IRAK1/4 Regulates IL-1beta and IL-6 in Sarcoidosis Alveolar Macrophages and Peripheral Blood Mononuclear Cells. AB - Sarcoidosis is a multisystem granulomatous disease of unknown etiology that primarily affects the lungs. Our previous work indicates that activation of p38 plays a pivotal role in sarcoidosis inflammatory response. Therefore, we investigated the upstream kinase responsible for activation of p38 in sarcoidosis alveolar macrophages (AMs) and PBMCs. We identified that sustained p38 phosphorylation in sarcoidosis AMs and PBMCs is associated with active MAPK kinase 4 but not with MAPK kinase 3/6. Additionally, we found that sarcoidosis AMs exhibit a higher expression of IRAK1, IRAK-M, and receptor interacting protein 2 (Rip2). Surprisingly, ex vivo treatment of sarcoidosis AMs or PBMCs with IRAK1/4 inhibitor led to a significant increase in IL-1beta mRNA expression both spontaneously and in response to TLR2 ligand. However, a combination of Rip2 and IRAK-1/4 inhibitors significantly decreased both IL-1beta and IL-6 production in sarcoidosis PBMCs and moderately in AMs. Importantly, a combination of Rip2 and IRAK-1/4 inhibitors led to decreased IFN-gamma and IL-6 and decreased percentage of activated CD4(+)CD25(+) cells in PBMCs. These data suggest that in sarcoidosis, both pathways, namely IRAK and Rip2, are deregulated. Targeted modulation of Rip2 and IRAK pathways may prove to be a novel treatment for sarcoidosis. PMID- 27402700 TI - Zbtb1 Safeguards Genome Integrity and Prevents p53-Mediated Apoptosis in Proliferating Lymphoid Progenitors. AB - Expression of the transcription factor Zbtb1 is required for normal lymphoid development. We report in the present study that Zbtb1 maintains genome integrity in immune progenitors, without which cells undergo increased DNA damage and p53 mediated apoptosis during replication and differentiation. Increased DNA damage in Zbtb1-mutant (ScanT) progenitors was due to increased sensitivity to replication stress, which was a consequence of inefficient activation of the S phase checkpoint response. Increased p53-mediated apoptosis affected not only lymphoid but also myeloid development in competitive bone marrow chimeras, and prevention of apoptosis by transgenic Bcl2 expression and p53 deficiency rescued lymphoid as well as myeloid development from Zbtb1-mutant progenitors. Interestingly, however, protection from apoptosis rescued only the early stages of T cell development, and thymocytes remained arrested at the double-negative 3 developmental stage, indicating a strict requirement of Zbtb1 at later T cell developmental stages. Collectively, these results indicate that Zbtb1 prevents DNA damage in replicating immune progenitors, allowing the generation of B cells, T cells, and myeloid cells. PMID- 27402701 TI - IL-10 Regulates Memory T Cell Development and the Balance between Th1 and Follicular Th Cell Responses during an Acute Viral Infection. AB - T cells provide protective immunity against infections by differentiating into effector cells that contribute to rapid pathogen control and by forming memory populations that survive over time and confer long-term protection. Thus, understanding the factors that regulate the development of effective T cell responses is beneficial for the design of vaccines and immune-based therapies against infectious diseases. Cytokines play important roles in shaping T cell responses, and IL-10 has been shown to modulate the differentiation of CD4 and CD8 T cells. In this study, we report that IL-10 functions in a cell-extrinsic manner early following acute lymphocytic choriomeningitis virus infection to suppress the magnitude of effector Th1 responses as well as the generation of memory CD4 and CD8 T cells. We further demonstrate that the blockade of IL-10 signaling during the priming phase refines the functional quality of memory CD4 and CD8 T cells. This inhibition strategy resulted in a lower frequency of virus specific follicular Th (Tfh) cells and increased the Th1 to Tfh ratio. Nevertheless, neither germinal center B cells nor lymphocytic choriomeningitis virus-specific Ab levels were influenced by the blockade. Thus, our studies show that IL-10 influences the balance between Th1 and Tfh cell differentiation and negatively regulates the development of functionally mature memory T cells. PMID- 27402702 TI - G2A Signaling Dampens Colitic Inflammation via Production of IFN-gamma. AB - Proinflammatory consequences have been described for lysophosphatidylcholine, a lipid product of cellular injury, signaling via the G protein-coupled receptor G2A on myeloid and lymphoid inflammatory cells. This prompted the hypothesis that genetic deletion of G2A would limit intestinal inflammation in a mouse model of colitis induced by dextran sodium sulfate. Surprisingly, G2A(-/-) mice exhibited significantly worsened colitis compared with wild-type mice, as demonstrated by disease activity, colon shortening, histology, and elevated IL-6 and IL-5 in colon tissues. Investigation of inflammatory cells recruited to inflamed G2A(-/-) colons showed significantly more TNF-alpha(+) and Ly6C(hi)MHCII(-) proinflammatory monocytes and eosinophils than in wild-type colons. Both monocytes and eosinophils were pathogenic as their depletion abolished the excess inflammation in G2A(-/-) mice. G2A(-/-) mice also had less IFN-gamma in inflamed colon tissues than wild-type mice. Fewer CD4(+) lymphocytes were recruited to inflamed G2A(-/-) colons, and fewer colonic lymphocytes produced IFN-gamma upon ex vivo stimulation. Administration of IFN-gamma to G2A(-/-) mice during dextran sodium sulfate exposure abolished the excess colitic inflammation and reduced colonic IL-5 and eosinophil numbers to levels seen in wild-type mice. Furthermore, IFN-gamma reduced the numbers of TNF-alpha(+) monocyte and enhanced their maturation from Ly6C(hi)MHCII(-) to Ly6C(int)MHCII(+) Taken together, the data suggest that G2A signaling serves to dampen intestinal inflammation via the production of IFN-gamma, which, in turn, enhances monocyte maturation to a less inflammatory program and ultimately reduces eosinophil-induced injury of colonic tissues. PMID- 27402704 TI - Occupational injustice: A critique. AB - BACKGROUND: Although the idea of occupational injustice pervades the occupational therapy literature, there has been little scholarly debate concerning this construct or the parameters of the five identified forms of occupational injustice. PURPOSE: The aims of this paper are to highlight conceptual confusions, foreground some inherent questions that have been neither acknowledged nor addressed, and question the theoretical and practical utility of five manifestations of occupational injustice. KEY ISSUES: Few theorists have contributed to the occupational injustice literature. Significant definitional confusion exists concerning the five forms of occupational injustice with some forms described as subsets of others. The inherent problems of judging occupational injustice have not been addressed. IMPLICATIONS: If occupational injustice were understood as a violation of occupational rights-human rights to achieve well-being through occupation-many of the problems of identifying a situation of occupational justice or injustice would be resolved. Using the capabilities approach to human rights would facilitate this endeavour. PMID- 27402703 TI - Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity. AB - Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally been quantified by the strength of the interaction, that is, the binding affinity, yet it has been shown that the stability of the peptide-MHC-I complex is a better correlate of immunogenicity compared with binding affinity. In this study, we have experimentally analyzed peptide-MHC-I complex stability of a large panel of human MHC-I allotypes and generated a body of data sufficient to develop a neural network-based pan-specific predictor of peptide-MHC-I complex stability. Integrating the neural network predictors of peptide-MHC-I complex stability with state-of-the-art predictors of peptide-MHC-I binding is shown to significantly improve the prediction of CTL epitopes. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCstabpan. PMID- 27402705 TI - Critical reflections on occupational justice: Toward a rights-based approach to occupational opportunities. AB - BACKGROUND: Occupational justice is cited throughout the occupational science and occupational therapy literatures despite little scholarly attention either to its definition or to how situations of occupational justice are identifiable. PURPOSE: This paper aims to contribute a critique of occupational justice, explore the concepts of justice and (occupational) rights, and support a capabilities approach to inform rights-based occupational therapy practices. KEY ISSUES: No clear definition of occupational justice or differentiation from social justice exists despite the longevity of the concept, and theorists frequently confuse the concepts of justice and rights. A rights-based focus provides an unambiguous mandate for occupational therapists, with the capabilities approach offering a cross-disciplinary framework to inform rights based practices. IMPLICATIONS: The concept of occupational rights is consistent with the rights-based focus advocated by the disabled people's movement, articulated by the United Nations' Convention on the Rights of Persons With Disabilities, and affirmed by the World Federation of Occupational Therapists' position on the centrality of occupation to health, well-being, and human rights. PMID- 27402706 TI - Wallenda/DLK protein levels are temporally downregulated by Tramtrack69 to allow R7 growth cones to become stationary boutons. AB - Dual leucine zipper kinase (DLK) promotes growth cone motility and must be restrained to ensure normal development. PHR (Pam/Highwire/RPM-1) ubiquitin ligases therefore target DLK for degradation unless axon injury occurs. Overall DLK levels decrease during development, but how DLK levels are regulated within a developing growth cone has not been examined. We analyzed the expression of the fly DLK Wallenda (Wnd) in R7 photoreceptor growth cones as they halt at their targets and become presynaptic boutons. We found that Wnd protein levels are repressed by the PHR protein Highwire (Hiw) during R7 growth cone halting, as has been observed in other systems. However, as R7 growth cones become boutons, Wnd levels are further repressed by a temporally expressed transcription factor, Tramtrack69 (Ttk69). Previously unobserved negative feedback from JNK also contributes to Wnd repression at both time points. We conclude that neurons deploy additional mechanisms to downregulate DLK as they form stable, synaptic connections. We use live imaging to probe the effects of Wnd and Ttk69 on R7 bouton development and conclude that Ttk69 coordinates multiple regulators of this process. PMID- 27402707 TI - Fgf signalling controls diverse aspects of fin regeneration. AB - Studies have shown that fibroblast growth factor (Fgf) signalling is necessary for appendage regeneration, but its exact function and the ligands involved during regeneration have not yet been elucidated. Here, we performed comprehensive expression analyses and identified fgf20a and fgf3/10a as major Fgf ligands in the wound epidermis and blastema, respectively. To reveal the target cells and processes of Fgf signalling, we performed a transplantation experiment of mesenchymal cells that express the dominant-negative Fgf receptor 1 (dnfgfr1) under control of the heat-shock promoter. This mosaic knockdown analysis suggested that Fgf signalling is directly required for fin ray mesenchyme to form the blastema at the early pre-blastema stage and to activate the regenerative cell proliferation at a later post-blastema stage. These results raised the possibility that the early epidermal Fgf20a and the later blastemal Fgf3/10a could be responsible for these respective processes. We demonstrated by gain-of function analyses that Fgf20a induces the expression of distal blastema marker junbl, and that Fgf3 promotes blastema cell proliferation. Our study highlights that Fgfs in the wound epidermis and blastema have distinct functions to regulate fin regeneration cooperatively. PMID- 27402708 TI - Shh and ZRS enhancer colocalisation is specific to the zone of polarising activity. AB - Limb-specific Shh expression is regulated by the (~1 Mb distant) ZRS enhancer. In the mouse, limb bud-restricted spatiotemporal Shh expression occurs from ~E10 to E11.5 at the distal posterior margin and is essential for correct autopod formation. Here, we have analysed the higher-order chromatin conformation of Shh in expressing and non-expressing tissues, both by fluorescence in situ hybridisation (FISH) and by chromosome conformation capture (5C). Conventional and super-resolution light microscopy identified significantly elevated frequencies of Shh/ZRS colocalisation only in the Shh-expressing regions of the limb bud, in a conformation consistent with enhancer-promoter loop formation. However, in all tissues and at all developmental stages analysed, Shh-ZRS spatial distances were still consistently shorter than those to a neural enhancer located between Shh and ZRS in the genome. 5C identified a topologically associating domain (TAD) over the Shh/ZRS genomic region and enriched interactions between Shh and ZRS throughout E11.5 embryos. Shh/ZRS colocalisation, therefore, correlates with the spatiotemporal domain of limb bud-specific Shh expression, but close Shh and ZRS proximity in the nucleus occurs regardless of whether the gene or enhancer is active. We suggest that this constrained chromatin configuration optimises the opportunity for the active enhancer to locate and instigate the expression of Shh. PMID- 27402710 TI - Bacterial community composition in relation to bedrock type and macrobiota in soils from the Sor Rondane Mountains, East Antarctica. AB - Antarctic soils are known to be oligotrophic and of having low buffering capacities. It is expected that this is particularly the case for inland high altitude regions. We hypothesized that the bedrock type and the presence of macrobiota in these soils enforce a high selective pressure on their bacterial communities. To test this, we analyzed the bacterial community structure in 52 soil samples from the western Sor Rondane Mountains (Dronning Maud Land, East Antarctica), using the Illumina MiSeq platform in combination with ARISA fingerprinting. The samples were taken along broad environmental gradients in an area covering nearly 1000 km(2) Ordination and variation partitioning analyses revealed that the total organic carbon content was the most significant variable in structuring the bacterial communities, followed by pH, electric conductivity, bedrock type and the moisture content, while spatial distance was of relatively minor importance. Acidobacteria (Chloracidobacteria) and Actinobacteria (Actinomycetales) dominated gneiss derived mineral soil samples, while Proteobacteria (Sphingomonadaceae), Cyanobacteria, Armatimonadetes and candidate division FBP-dominated soil samples with a high total organic carbon content that were mainly situated on granite derived bedrock. PMID- 27402712 TI - Planktic Tychonema (Cyanobacteria) in the large lakes south of the Alps: phylogenetic assessment and toxigenic potential. AB - This work allowed assessing a widespread occurrence of Tychonema bourrellyi in the largest lakes south of the Alps (Garda, Iseo, Como and Maggiore). The taxonomy of the species was confirmed adopting a polyphasic approach, which included microscopic examinations, molecular (16S rRNA and rbcLX sequences) and (Lake Garda) ecological characterisations. Over 70% of the 36 isolates of Tychonema sampled from the four lakes tested positive for the presence of genes implicated in the biosynthesis of anatoxins (anaF and/or anaC) and for the production of anatoxin-a (ATX) and homoanatoxin-a (HTX). A detailed analysis carried out in Lake Garda showed strong ongoing changes in the cyanobacterial community, with populations of Tychonema developing with higher biovolumes compared to the microcystins (MCs) producer Planktothrix rubescens Moreover, the time * depth distribution of Tychonema was paralleled by a comparable distribution of ATX and HTX. The increasing importance of Tychonema in Lake Garda was also suggested by the opposite trends of ATX and MCs observed since 2009. These results suggest that radical changes are occurring in the largest lakes south of the Alps. Their verification and implications will require to be assessed by extending a complete experimental work to the other large perialpine lakes. PMID- 27402711 TI - Impact of reducing and oxidizing agents on the infectivity of Qbeta phage and the overall structure of its capsid. AB - Qbeta phages infect Escherichia coli in the human gut by recognizing F-pili as receptors. Infection therefore occurs under reducing conditions induced by physiological agents (e.g. glutathione) or the intestinal bacterial flora. After excretion in the environment, phage particles are exposed to oxidizing conditions and sometimes disinfection. If inactivation does not occur, the phage may infect new hosts in the human gut through the oral route. During such a life cycle, we demonstrated that, outside the human gut, cysteines of the major protein capsid of Qbeta phage form disulfide bonds. Disinfection with NaClO does not allow overoxidation to occur. Such oxidation induces inactivation rather by irreversible damage to the minor proteins. In the presence of glutathione, most disulfide bonds are reduced, which slightly increases the capacity of the phage to infect E. coli in vitro Such reduction is reversible and barely alters infectivity of the phage. Reduction of all disulfide bonds by dithiothreitol leads to complete capsid destabilization. These data provide new insights into how the phages are impacted by oxidizing-reducing conditions outside their host cell and raises the possibility of the intervention of the redox during life cycle of the phage. PMID- 27402709 TI - RBOH-mediated ROS production facilitates lateral root emergence in Arabidopsis. AB - Lateral root (LR) emergence represents a highly coordinated process in which the plant hormone auxin plays a central role. Reactive oxygen species (ROS) have been proposed to function as important signals during auxin-regulated LR formation; however, their mode of action is poorly understood. Here, we report that Arabidopsis roots exposed to ROS show increased LR numbers due to the activation of LR pre-branch sites and LR primordia (LRP). Strikingly, ROS treatment can also restore LR formation in pCASP1:shy2-2 and aux1 lax3 mutant lines in which auxin mediated cell wall accommodation and remodeling in cells overlying the sites of LR formation is disrupted. Specifically, ROS are deposited in the apoplast of these cells during LR emergence, following a spatiotemporal pattern that overlaps the combined expression domains of extracellular ROS donors of the RESPIRATORY BURST OXIDASE HOMOLOGS (RBOH). We also show that disrupting (or enhancing) expression of RBOH in LRP and/or overlying root tissues decelerates (or accelerates) the development and emergence of LRs. We conclude that RBOH-mediated ROS production facilitates LR outgrowth by promoting cell wall remodeling of overlying parental tissues. PMID- 27402713 TI - Identifying the key taxonomic categories that characterize microbial community diversity using full-scale classification: a case study of microbial communities in the sediments of Hangzhou Bay. AB - Coastal areas are land-sea transitional zones with complex natural and anthropogenic disturbances. Microorganisms in coastal sediments adapt to such disturbances both individually and as a community. The microbial community structure changes spatially and temporally under environmental stress. In this study, we investigated the microbial community structure in the sediments of Hangzhou Bay, a seriously polluted bay in China. In order to identify the roles and contribution of all microbial taxa, we set thresholds as 0.1% for rare taxa and 1% for abundant taxa, and classified all operational taxonomic units into six exclusive categories based on their abundance. The results showed that the key taxa in differentiating the communities are abundant taxa (AT), conditionally abundant taxa (CAT), and conditionally rare or abundant taxa (CRAT). A large population in conditionally rare taxa (CRT) made this category collectively significant in differentiating the communities. Both bacteria and archaea demonstrated a distance decay pattern of community similarity in the bay, and this pattern was strengthened by rare taxa, CRT and CRAT, but weakened by AT and CAT. This implied that the low abundance taxa were more deterministically distributed, while the high abundance taxa were more ubiquitously distributed. PMID- 27402714 TI - Diversity of fungal endophytes in recent and ancient wheat ancestors Triticum dicoccoides and Aegilops sharonensis. AB - Endophytes have profound impacts on plants, including beneficial effects on agriculturally important traits. We hypothesized that endophytes in wild plants include beneficial endophytes that are absent or underrepresented in domesticated crops. In this work, we studied the structure of endophyte communities in wheat related grasses, Triticum dicoccoides and Aegilops sharonensis, and compared it to an endophyte community from wheat (T. aeastivum). Endophytes were isolated by cultivation and by cultivation-independent methods. In total, 514 intergenic spacer region sequences from single cultures were analyzed. Categorization at 97% sequence similarity resulted in 67 operational taxonomic units (OTUs) that were evenly distributed between the different plant species. A narrow core community of Alternaria spp. was found in all samples, but each plant species also contained a significant portion of unique endophytes. The cultivation-independent analysis identified a larger number of OTUs than the cultivation method, half of which were singletons or doubletons. For OTUs with a relative abundance >0.5%, similar numbers were obtained by both methods. Collectively, our data show that wild grass relatives of wheat contain a wealth of taxonomically diverse fungal endophytes that are not found in modern wheat, some of which belong to taxa with known beneficial effects. PMID- 27402715 TI - Multiscale assemblage of an ectomycorrhizal fungal community: the influence of host functional traits and soil properties in a 10-ha miombo forest. AB - Ectomycorrhizal fungi (EMF) are highly diversified and dominant in a number of forest ecosystems. Nevertheless, their scales of spatial distribution and the underlying ecological processes remain poorly understood. Although most EMF are considered to be generalists regarding host identity, a preference toward functional strategies of host trees has never been tested. Here, the EMF community was characterised by DNA sequencing in a 10-ha tropical dry season forest-referred to as miombo-an understudied ecosystem from a mycorrhizal perspective. We used 36 soil parameters and 21 host functional traits (FTs) as candidate explanatory variables in spatial constrained ordinations for explaining the EMF community assemblage. Results highlighted that the community variability was explained by host FTs related to the 'leaf economics spectrum' (adjusted R(2) = 11%; SLA, leaf area, foliar Mg content), and by soil parameters (adjusted R(2) = 17%), notably total forms of micronutrients or correlated available elements (Al, N, K, P). Both FTs and soil generated patterns in the community at scales ranging from 75 to 375 m. Our results indicate that soil is more important than previously thought for EMF in miombo woodlands, and show that FTs of host species can be better predictors of symbiont distribution than taxonomical identity. PMID- 27402716 TI - Lichen Planus Pigmentosus-like Reaction to Guasha. AB - BACKGROUND AND OBJECTIVE: Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus (LP) that manifests as macular hyperpigmentation involving chiefly the face and upper limbs. Although its etiology has not been fully elucidated, a relationship with hepatitis C infection, restrictive underwear, localized friction, and sun exposure have been proposed. Rarely, exposure to mustard oil, amla oil, henna, or hair dyes has been reported. CONCLUSION: We herein describe an LPP-like reaction to Guasha. PMID- 27402717 TI - Psoriasis Patients Treated With Biologics and Methotrexate Have a Reduced Rate of Myocardial Infarction: A Collaborative Analysis Using International Cohorts. AB - Psoriasis is a chronic inflammatory skin condition characterised by the formation of red scaly plaques on the skin. It is an autoimmune disease cause by the dysregulation of cytokines controlling the inflammatory pathways, a mechanism likely contributing to various comorbidities observed in patients with psoriasis. Cardiovascular disease is one comorbidity observed more frequently in the psoriasis patient population. Biologic treatments specifically target the dysregulation of cytokines in the inflammation pathway and have shown to be an effective treatment for moderate to severe psoriasis where other systemic treatments have failed. More recently, biologics have been shown to reduce the incidence of myocardial infarction in patients with psoriasis compared to patients treated with topical agents. In the present study, 4 international psoriasis patient cohorts are combined and analyzed to examine the effect that biologic or methotrexate treatment has on reducing the incidence of myocardial infarction. Both methotrexate and biologic treatments were found to lower the incidence of myocardial infarction in moderate to severe psoriasis patient populations. PMID- 27402718 TI - Public Policy Involvement by Certified Health Education Specialists: Results of a National Study. AB - BACKGROUND: Advocating for health-related activities is an essential part of being a health educator and knowing how to advocate is an important part of the Certified Health Education Specialist (CHES) exam. However, based on previous research, there may be a gap between knowing how to and actually participating in public policy activities. The purpose of this study was to determine public policy involvement of CHES. METHOD: Surveys were mailed to a random sample of 500 CHES (41% response rate). RESULTS: The highest selected public policy activities by CHES were the following: voting at an election (88.9%), contacting a public office (49%), and providing policy-related information (42.9%). The number of locations CHES individuals selected in having training on advocacy was a predictive factor in their confidence to perform advocacy. Positive correlations between perceived knowledge and effectiveness of the public policy process and self-reported involvement in public policy were found. CONCLUSION: Although there is moderate self-reported involvement in public policy activities, more emphasis needs to be placed on raising the confidence of CHES to perform advocacy-related activities in the field. PMID- 27402719 TI - State Tobacco Control Program Implementation Strategies for Smoke-Free Multiunit Housing. AB - Multiunit housing residents are at risk of secondhand smoke exposure from adjoining units and common areas. We developed this case study to document state level strategies undertaken to address this risk. We explored program documents to identify facilitators, barriers, and outcomes. Three states (Montana, Michigan, and Nebraska) provided detailed information on multiunit housing efforts in the study time frame. We conducted a qualitative analysis using inductive coding to develop themes. Several facilitators relating to existing infrastructure included traditional and nontraditional partnerships, leadership and champions, collecting and using data, efficient use of resources, and strategic plans. We also report external catalysts, barriers, and outcomes. Significant state leadership and effort were required to provide local-level technical assistance to engage traditional and nontraditional partners. Information needs were identified and varied by stakeholder type (i.e., health vs. housing). States recommend starting with public housing authorities, so they can become resources for affordable and subsidized housing. These lessons and resources can be used to inform smoke-free multiunit housing initiatives in other states and localities. PMID- 27402720 TI - Expanding the Reach of Evidence-Based Self-Management Education and Physical Activity Interventions: Results of a Cross-Site Evaluation of State Health Departments. AB - Participation in community-based self-management education and physical activity interventions has been demonstrated to improve quality of life for those who have arthritis and other chronic diseases. The Centers for Disease Control and Prevention Arthritis Program funded 21 state health departments to expand the reach (defined as the number of people who participate in interventions) of 10 evidence-based interventions in community settings. The Arthritis Centralized Evaluation assessed the strategies and tactics used by state health departments to expand the reach of these evidence-based interventions. The evaluation compared and contrasted processes used by the states to expand reach. Engaging multisite delivery system partners, prioritizing reach, embedding interventions within partners' routine operations, and collaborating across chronic disease program areas were all dissemination strategies that were correlated with expanded intervention reach. However, states also encountered challenges that limited their ability to successfully engage delivery systems as partners. These barriers included difficulty identifying delivery system partners and the lengthy time periods partners needed to adopt and embed the interventions. PMID- 27402721 TI - The Power of Digital Storytelling as a Culturally Relevant Health Promotion Tool. AB - Digital storytelling is an emergent method in health promotion. It addresses health inequities by combining technology with the voices of members of vulnerable, often underrepresented populations. The overall goal of this pilot project was to explore if digital storytelling could be a culturally relevant health promotion tool for Hispanics/Latinos to share their experiences with cancer, or other diseases. Promotores participated in a train-the-trainer workshop. Community members worked with trained promotores to create digital stories through community workshops. We conducted one-on-one interviews with digital story creators to elicit perspectives and assess their experience. One overarching theme among storytellers was the power of storytelling. Supporting subthemes that emerged in the interviews were (1) connection and communication, (2) lack of opportunities and barriers to telling stories, and (3) potential for disease prevention awareness and education. This study found digital storytelling to be culturally relevant for Hispanics/Latinos of Mexican origin. For these storytellers it was a uniquely valuable tool for sharing personal stories of overcoming or managing health issues. Participants found the digital story experience to be positive and beneficial. It provided a healing outlet to reflect on a difficult experience and find support within one's own community. PMID- 27402722 TI - Primary Care Resident Training for Obesity, Nutrition, and Physical Activity Counseling: A Mixed-Methods Study. AB - National guidelines have been established to support the role of primary care physicians in addressing obesity. Preparing primary care residents to recognize and treat overweight/obesity has been identified as an essential component of postgraduate medical training that is currently lacking. This study aims to identify how primary care residency programs are preparing physicians to counsel about obesity, nutrition, and physical activity (ONPA) and to examine program members' perspectives regarding the place of ONPA counseling in the curriculum, and its relevance in primary care training. Using mixed methods, we collected and analyzed data on 25 family medicine, internal medicine, and obstetrics/gynecology residency programs across Ohio. Programs averaged 2.8 hours of ONPA-related didactics per year. Ten programs (42%) taught techniques for health behavior counseling. Having any ONPA-related didactics was associated with greater counseling knowledge (p = .01) among residents but poorer attitudes (p < .001) and poorer perceived professional norms (p = .004) toward ONPA counseling. Findings from interview data highlighted similar perceived barriers to ONPA counseling across all three specialties but variation in perception of responsibility to provide ONPA counseling. While widespread expectations that primary care physicians counsel their overweight and obese patients prevail, few residency programs provide training to support such counseling. PMID- 27402723 TI - BMI as a Modifiable Risk Factor for Type 2 Diabetes: Refining and Understanding Causal Estimates Using Mendelian Randomization. AB - This study focused on resolving the relationship between BMI and type 2 diabetes. The availability of multiple variants associated with BMI offers a new chance to resolve the true causal effect of BMI on type 2 diabetes; however, the properties of these associations and their validity as genetic instruments need to be considered alongside established and new methods for undertaking Mendelian randomization (MR). We explore the potential for pleiotropic genetic variants to generate bias, revise existing estimates, and illustrate value in new analysis methods. A two-sample MR approach with 96 genetic variants was used with three different analysis methods, two of which (MR-Egger and the weighted median) have been developed specifically to address problems of invalid instrumental variables. We estimate an odds ratio for type 2 diabetes per unit increase in BMI (kg/m(2)) of between 1.19 and 1.38, with the most stable estimate using all instruments and a weighted median approach (1.26 [95% CI 1.17, 1.34]). TCF7L2(rs7903146) was identified as a complex effect or pleiotropic instrument, and removal of this variant resulted in convergence of causal effect estimates from different causal analysis methods. This indicated the potential for pleiotropy to affect estimates and differences in performance of alternative analytical methods. In a real type 2 diabetes-focused example, this study demonstrates the potential impact of invalid instruments on causal effect estimates and the potential for new approaches to mitigate the bias caused. PMID- 27402725 TI - A Comparison of Biological and Physical Risk Factors for Cardiovascular Disease in Overweight/Obese Individuals With and Without Prediabetes. AB - Compared with type 2 diabetes, evaluating the direct biological and physical risk factors for cardiovascular disease (CVD) in overweight/obese adults with and without prediabetes is less understood. Therefore, the aim of the study was to compare baseline biological and physical risk factors for CVD among overweight/obese adults with and without prediabetes. A secondary data analysis was performed. Three hundred forty-one overweight/obese participants were included in the analysis. Compared with non-prediabetics, prediabetics had higher fasting blood glucose, body mass index, waist-to-hip ratio, and triglycerides. Prediabetics were also more likely to be insulin resistant than non-prediabetics. Participants with prediabetes had much lower cardiorespiratory fitness than those without prediabetes. Findings from this study suggest that healthy overweight/obese adults with prediabetes were likely at higher biological and physical risk of CVD at baseline compared with those without prediabetes. Early intervention to improve CVD risk progression among persons with prediabetes is essential. PMID- 27402724 TI - Measuring Racial/Ethnic Disparities in Mental Health Service Use Among Children Referred to the Child Welfare System. AB - This study aims to compare different approaches to measuring racial/ethnic disparities in mental health (MH) service use among a nationwide representative sample of children referred to the child welfare system and compare the magnitude and direction of potential disparities in MH service use over time. Using data from the National Survey of Child and Adolescent Well-Being, six summary measures of disparity were implemented to quantify racial/ethnic disparities in MH service use. This study found that youth of color were less likely than their White counterparts to receive MH services. This racial/ethnic disparity was found to increase over time; however, the magnitude of the increase varied considerably across disparity measures. In addition, the estimated increases in disparity were even greater when the sample was limited to youth in need of MH services. This study shows that the same data may produce different magnitudes of disparity, depending on which metric is implemented and whether MH need is accounted for. A greater understanding of and justification for selection of methods to examine MH disparities among child welfare researchers and policy makers is warranted. PMID- 27402727 TI - Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide. AB - The existence of a glucuronide conjugate of the major circulating clopidogrel metabolites, called clopidogrel acyl glucuronide (CAG), is already known. However, information regarding its pharmacokinetics (PK), metabolism, and clearance are modest. We investigated in vivo the potential CAG trans esterification to clopidogrel (reaction occurring in vitro in particular conditions) by administering the metabolite to mice. Experiments were then carried out on men, clopidogrel administered alone or followed by activated charcoal intake (intestinal reabsorption blockade). Study objectives included: PK comparison of CAG, clopidogrel carboxylic acid (CCA), and clopidogrel in plasma, determination of their elimination patterns in urine and feces, and tracking of charcoal-induced changes in PK and/or urinary excretion that would indicate relevant enterohepatic recycling of CAG. In mice, CAG was rapidly hydrolyzed to CCA after oral administration, whereas by intravenous route metabolic conversion to CCA was delayed. No levels of clopidogrel were detected in mice plasma, excluding any potential trans-esterification or other form of back-conversion in vivo. PK experiments in man showed that CAG is hydrolyzed in the gastrointestinal tract (very low concentrations in feces), but there is no evidence of enterohepatic recirculation. Quantitation of the three moieties in stool samples accounted for only 1.2% of an administered dose, suggesting that other yet unknown metabolites/degradation products formed through metabolic processes and/or the activity of local microflora are mainly excreted by this route. In man CAG was confirmed as one of the major terminal metabolites of clopidogrel, with a PK behavior similar to CCA. PMID- 27402726 TI - The Absolute Bioavailability and Effect of Food on the Pharmacokinetics of Odanacatib: A Stable-Label i.v./Oral Study in Healthy Postmenopausal Women. AB - A stable-label i.v./oral study design was conducted to investigate the pharmacokinetics (PK) of odanacatib. Healthy, postmenopausal women received oral doses of unlabeled odanacatib administered simultaneously with a reference of 1 mg i.v. stable (13)C-labeled odanacatib. The absolute bioavailability of odanacatib was 30% at 50 mg (the phase 3 dose) and 70% at 10 mg, which is consistent with solubility-limited absorption. Odanacatib exposure (area under the curve from zero to infinity) increased by 15% and 63% when 50 mg was administered with low-fat and high-fat meals, respectively. This magnitude of the food effect is unlikely to be clinically important. The volume of distribution was ~100 liters. The clearance was ~0.8 l/h (13 ml/min), supporting that odanacatib is a low-extraction ratio drug. Population PK modeling indicated that 88% of individuals had completed absorption of >80% bioavailable drug within 24 hours, with modest additional absorption after 24 hours and periodic fluctuations in plasma concentrations contributing to late values for time to Cmax in some subjects. PMID- 27402728 TI - CYP3A Specifically Catalyzes 1beta-Hydroxylation of Deoxycholic Acid: Characterization and Enzymatic Synthesis of a Potential Novel Urinary Biomarker for CYP3A Activity. AB - The endogenous bile acid metabolite 1beta-hydroxy-deoxycholic acid (1beta-OH-DCA) excreted in human urine may be used as a sensitive CYP3A biomarker in drug development reflecting in vivo CYP3A activity. An efficient and stereospecific enzymatic synthesis of 1beta-OH-DCA was developed using a Bacillus megaterium (BM3) cytochrome P450 (P450) mutant, and its structure was confirmed by nuclear magnetic resonance (NMR) spectroscopy. A [(2)H4]-labeled analog of 1beta-OH-DCA was also prepared. The major hydroxylated metabolite of deoxycholic acid (DCA) in human liver microsomal incubations was identified as 1beta-OH-DCA by comparison with the synthesized reference analyzed by UPLC-HRMS. Its formation was strongly inhibited by CYP3A inhibitor ketoconazole. Screening of 21 recombinant human cytochrome P450 (P450) enzymes showed that, with the exception of extrahepatic CYP46A1, the most abundant liver P450 subfamily CYP3A, including CYP3A4, 3A5, and 3A7, specifically catalyzed 1beta-OH-DCA formation. This indicated that 1beta hydroxylation of DCA may be a useful marker reaction for CYP3A activity in vitro. The metabolic pathways of DCA and 1beta-OH-DCA in human hepatocytes were predominantly via glycine and, to a lesser extent, via taurine and sulfate conjugation. The potential utility of 1beta-hydroxylation of DCA as a urinary CYP3A biomarker was illustrated by comparing the ratio of 1beta-OH-DCA:DCA in a pooled spot urine sample from six healthy control subjects to a sample from one patient treated with carbamazepine, a potent CYP3A inducer; 1beta-OH-DCA:DCA was considerably higher in the patient versus controls (ratio 2.8 vs. 0.4). Our results highlight the potential of 1beta-OH-DCA as a urinary biomarker in clinical CYP3A DDI studies. PMID- 27402729 TI - Acute aerobic exercise increases implicit approach motivation for dessert images. AB - We examined the effect of acute exercise compared to a cognitive task on implicit approach/avoidance motivation to dessert food images using the Dessert-Approach Avoidance Task. Participants randomized to exercise had a greater increase in approach motivation to dessert images compared to those completing cognitive tasks ( p=0.046), adjusting for disordered eating, task difficulty, and changes in negative affect. This study provides the first evidence for the use of the Dessert-Approach-Avoidance Task to evaluate the effects of acute exercise on implicit motivations for dessert images. Future studies should examine implicit response to food images using the Dessert-Approach-Avoidance Task in response to chronic exercise. PMID- 27402730 TI - Health goals among American adults: Prevalence, characteristics, and barriers. AB - Although numerous factors have been demonstrated in laboratory settings to lead to more successful health goal attainment, their actual use in daily goal pursuit is unknown. This study examines spontaneously reported health goals and their characteristics in a sample of 557 American adults. Participants responded to questions about health and health goals, with items assessing motivation, social support, and implementation intentions. In all, 66 percent of respondents had a health goal, 26 percent of participants had implementation intentions, and 47 percent received support from close others. Results suggest that interventions should focus on encouraging goal setting, teaching implementation intentions, and educating close others in providing support. PMID- 27402731 TI - Self-compassion: An adaptive link between early memories and women's quality of life. AB - Research has emphasized the important role of recalling childhood experiences on adult mental health, and also the benefits of self-compassion on well-being. This study explored self-compassion as a mediator between early memories with family and peers and quality of life, on a wide age range female sample ( N = 645). Path analysis revealed that self-compassion mediated the impact of both types of memories on women's perceived quality of life. Overall, results revealed that the recall of early positive memories, either with family and peers, associate with a more compassionate self-to-self relationship, and the perception of greater psychological and social well-being. PMID- 27402732 TI - An analysis of the relationships between peer support and diabetes outcomes in adolescents with type 1 diabetes. AB - This study explores the relationships between the various subtypes of global and diabetes-specific peer support and health outcomes in adolescents with type 1 diabetes. Global peer support significantly predicted self-care and glycated haemoglobin, although no associations were identified for diabetes-specific support overall, nor its factors. When comparing participants with above or below average glycaemic control, significantly greater diabetes-specific support was reported in those with poorer control. It is suggested that this may be related to feelings of nagging, in which diabetes-specific support is perceived as harassment. PMID- 27402733 TI - Neonatal thyroid-stimulating hormone concentration and psychomotor development at preschool age. AB - OBJECTIVE: Thyroid hormones are essential for normal brain development. The aim of this study is to assess if high concentration of thyroid stimulating hormone (TSH) that is below the clinical threshold (5-15 mIU/L) at neonatal screening is linked to psychomotor development impairments in the offspring at preschool age. DESIGN: A total of 284 Belgian preschool children 4-6 years old and their mothers were included in the study. The children were randomly selected from the total list of neonates screened in 2008, 2009 and 2010 by the Brussels newborn screening centre. The sampling was stratified by gender and TSH range (0.45-15 mIU/L). Infants with congenital hypothyroidism (>15 mIU/L), low birth weight and/or prematurity were excluded. Psychomotor development was assessed using the Charlop-Atwell scale of motor coordination. The iodine status of children was determined using median urinary iodine concentration. Socioeconomic, parental and child potential confounding factors were measured through a self-administered questionnaire. RESULTS: TSH level was not significantly associated with total motor score (average change in z-score per unit increase in TSH is 0.02 (-0.03, 0.07), p=0.351), objective motor score (p=0.794) and subjective motor score (p=0.124). No significant associations were found using multivariate regression model to control confounding factors. CONCLUSIONS: Mild thyroid dysfunction in the newborn-reflected by an elevation of TSH that is below the clinical threshold (5-15 mIU/L)-was not associated with impaired psychomotor development at preschool age. PMID- 27402734 TI - Psychological maladjustment and quality of life in adolescents with constipation. AB - OBJECTIVES: To assess psychological maladjustment in adolescents with functional constipation. STUDY DESIGN: We conducted a cross-sectional survey in five schools. Adolescents aged between 13 and 18 years were included in the study. Validated questionnaires were used to collect bowel habits and demographic data, health-related quality of life (HRQoL) and psychological maladjustment. Rome III criteria were used to diagnose constipation. RESULTS: 1697 adolescents were recruited (boys 779 (45.9%), mean age 15.06 years and SD 1.6 years). Prevalence of constipation was 6.7%, of whom 52 were boys (45.6%) and 62 were girls (54.4%). 38 adolescents (33.3%) with constipation and 230 controls (14.5%) had significant psychological maladjustment. Among seven different personality dimensions used to assess psychological maladjustment, children with constipation had significantly more deficits than controls in hostility and aggression (14.2 vs 12.6 in controls (mean difference 1.54, 95% CI (0.89 to 2.19) p<0.001), negative self-esteem (12.0 vs 10.5 in controls, mean difference 1.54 95% CI (0.96 to 2.06) p<0.001), negative self-adequacy (11.9 vs 9.8 controls, mean difference 2.07 95% CI (1.46 to 2.67) p<0.001), emotional unresponsiveness (12.9 vs 11.5 controls, mean difference 1.44 95% CI (0.84 to 2.04) p<0.001), emotional instability (17.1 vs 15.6, mean difference 1.53 95% CI (0.86 to 2.2) p<0.001) and negative world view (12.1 vs 10.2 controls, mean difference 1.91 95% CI (1.24 to 2.59) p<0.001). The total HRQoL of adolescents with constipation was lower than controls (70.6 vs 79.0 mean difference 9.48 95% CI (1.4 to 6.7) p<0.05). CONCLUSION: A significant proportion of children with constipation are suffering from psychological maladjustment. PMID- 27402735 TI - Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study. AB - The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded. PMID- 27402736 TI - Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers. AB - Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments. PMID- 27402737 TI - Multicellularity makes somatic differentiation evolutionarily stable. AB - Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation. PMID- 27402738 TI - Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke. AB - Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain-behavior relationships in stroke. PMID- 27402739 TI - Left cortical specialization for visual letter strings predicts rudimentary knowledge of letter-sound association in preschoolers. AB - Reading, one of the most important cultural inventions of human society, critically depends on posterior brain areas of the left hemisphere in proficient adult readers. In children, this left hemispheric cortical specialization for letter strings is typically detected only after approximately 1 y of formal schooling and reading acquisition. Here, we recorded scalp electrophysiological (EEG) brain responses in 5-y-old (n = 40) prereaders presented with letter strings appearing every five items in rapid streams of pseudofonts (6 items per second). Within 2 min of recording only, letter strings evoked a robust specific response over the left occipito-temporal cortex at the predefined frequency of 1.2 Hz (i.e., 6 Hz/5). Interindividual differences in the amplitude of this electrophysiological response are significantly related to letter knowledge, a preschool predictor of later reading ability. These results point to the high potential of this rapidly collected behavior-free measure to assess reading ability in developmental populations. These findings were replicated in a second experiment (n = 26 preschool children), where familiar symbols and line drawings of objects evoked right-lateralized and bilaterally specific responses, respectively, showing the specificity of the early left hemispheric dominance for letter strings. Collectively, these findings indicate that limited knowledge of print in young children, before formal education, is sufficient to develop specialized left lateralized neuronal circuits, thereby pointing to an early onset and rapid impact of left hemispheric reentrant sound mapping on posterior cortical development. PMID- 27402740 TI - Delayed mortality effects cut the malaria transmission potential of insecticide resistant mosquitoes. AB - Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide resistant vectors by two-thirds, with delayed effects accounting for at least one half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance. PMID- 27402741 TI - Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling. AB - Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ~1-um intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID- 27402742 TI - Genetic evidence for natural selection in humans in the contemporary United States. AB - Recent findings from molecular genetics now make it possible to test directly for natural selection by analyzing whether genetic variants associated with various phenotypes have been under selection. I leverage these findings to construct polygenic scores that use individuals' genotypes to predict their body mass index, educational attainment (EA), glucose concentration, height, schizophrenia, total cholesterol, and (in females) age at menarche. I then examine associations between these scores and fitness to test whether natural selection has been occurring. My study sample includes individuals of European ancestry born between 1931 and 1953 who participated in the Health and Retirement Study, a representative study of the US population. My results imply that natural selection has been slowly favoring lower EA in both females and males, and are suggestive that natural selection may have favored a higher age at menarche in females. For EA, my estimates imply a rate of selection of about -1.5 mo of education per generation (which pales in comparison with the increases in EA observed in contemporary times). Although they cannot be projected over more than one generation, my results provide additional evidence that humans are still evolving-albeit slowly, especially compared with the rapid changes that have occurred over the past few generations due to cultural and environmental factors. PMID- 27402743 TI - Utility functions predict variance and skewness risk preferences in monkeys. AB - Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals' preferences followed both second order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals' preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys' choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences. PMID- 27402744 TI - Peer review and competition in the Art Exhibition Game. AB - To investigate the effect of competitive incentives under peer review, we designed a novel experimental setup called the Art Exhibition Game. We present experimental evidence of how competition introduces both positive and negative effects when creative artifacts are evaluated and selected by peer review. Competition proved to be a double-edged sword: on the one hand, it fosters innovation and product diversity, but on the other hand, it also leads to more unfair reviews and to a lower level of agreement between reviewers. Moreover, an external validation of the quality of peer reviews during the laboratory experiment, based on 23,627 online evaluations on Amazon Mechanical Turk, shows that competition does not significantly increase the level of creativity. Furthermore, the higher rejection rate under competitive conditions does not improve the average quality of published contributions, because more high-quality work is also rejected. Overall, our results could explain why many ground breaking studies in science end up in lower-tier journals. Differences and similarities between the Art Exhibition Game and scholarly peer review are discussed and the implications for the design of new incentive systems for scientists are explained. PMID- 27402746 TI - Correction for Traverse and Ochman, Conserved rates and patterns of transcription errors across bacterial growth states and lifestyles. PMID- 27402745 TI - Assignment of function to a domain of unknown function: DUF1537 is a new kinase family in catabolic pathways for acid sugars. AB - Using a large-scale "genomic enzymology" approach, we (i) assigned novel ATP dependent four-carbon acid sugar kinase functions to members of the DUF1537 protein family (domain of unknown function; Pfam families PF07005 and PF17042) and (ii) discovered novel catabolic pathways for d-threonate, l-threonate, and d erythronate. The experimentally determined ligand specificities of several solute binding proteins (SBPs) for TRAP (tripartite ATP-independent permease) transporters for four-carbon acids, including d-erythronate and l-erythronate, were used to constrain the substrates for the catabolic pathways that degrade the SBP ligands to intermediates in central carbon metabolism. Sequence similarity networks and genome neighborhood networks were used to identify the enzyme components of the pathways. Conserved genome neighborhoods encoded SBPs as well as permease components of the TRAP transporters, members of the DUF1537 family, and a member of the 4-hydroxy-l-threonine 4-phosphate dehydrogenase (PdxA) oxidative decarboxylase, class II aldolase, or ribulose 1,5-bisphosphate carboxylase/oxygenase, large subunit (RuBisCO) superfamily. Because the characterized substrates of members of the PdxA, class II aldolase, and RuBisCO superfamilies are phosphorylated, we postulated that the members of the DUF1537 family are novel ATP-dependent kinases that participate in catabolic pathways for four-carbon acid sugars. We determined that (i) the DUF1537/PdxA pair participates in a pathway for the conversion of d-threonate to dihydroxyacetone phosphate and CO2 and (ii) the DUF1537/class II aldolase pair participates in pathways for the conversion of d-erythronate and l-threonate (epimers at carbon 3) to dihydroxyacetone phosphate and CO2 The physiological importance of these pathways was demonstrated in vivo by phenotypic and genetic analyses. PMID- 27402747 TI - Groundwater methane in relation to oil and gas development and shallow coal seams in the Denver-Julesburg Basin of Colorado. AB - Unconventional oil and gas development has generated intense public concerns about potential impacts to groundwater quality. Specific pathways of contamination have been identified; however, overall rates of contamination remain ambiguous. We used an archive of geochemical data collected from 1988 to 2014 to determine the sources and occurrence of groundwater methane in the Denver Julesburg Basin of northeastern Colorado. This 60,000-km(2) region has a 60-y long history of hydraulic fracturing, with horizontal drilling and high-volume hydraulic fracturing beginning in 2010. Of 924 sampled water wells in the basin, dissolved methane was detected in 593 wells at depths of 20-190 m. Based on carbon and hydrogen stable isotopes and gas molecular ratios, most of this methane was microbially generated, likely within shallow coal seams. A total of 42 water wells contained thermogenic stray gas originating from underlying oil and gas producing formations. Inadequate surface casing and leaks in production casing and wellhead seals in older, vertical oil and gas wells were identified as stray gas migration pathways. The rate of oil and gas wellbore failure was estimated as 0.06% of the 54,000 oil and gas wells in the basin (lower estimate) to 0.15% of the 20,700 wells in the area where stray gas contamination occurred (upper estimate) and has remained steady at about two cases per year since 2001. These results show that wellbore barrier failure, not high-volume hydraulic fracturing in horizontal wells, is the main cause of thermogenic stray gas migration in this oil- and gas-producing basin. PMID- 27402748 TI - IL-17A-producing resident memory gammadelta T cells orchestrate the innate immune response to secondary oral Listeria monocytogenes infection. AB - Memory gammadelta T cells are important for the clearance of Listeria monocytogenes infection in the intestinal mucosa. However, the mechanisms by which memory gammadelta T cells provide protection against secondary oral infection are poorly understood. Here we used a recombinant strain of L. monocytogenes that efficiently invades the intestinal epithelium to show that Vgamma4(+) memory gammadelta T cells represent a resident memory (Trm) population in the mesenteric lymph nodes (MLNs). The gammadelta Trm exhibited a remarkably static pattern of migration that radically changed following secondary oral L. monocytogenes infection. The gammadelta Trms produced IL-17A early after rechallenge and formed organized clusters with myeloid cells surrounding L. monocytogenes replication foci only after a secondary oral infection. Antibody blocking studies showed that in addition to IL-17A, the chemokine receptor C-X-C chemokine receptor 3 (CXCR3) is also important to enable the local redistribution of gammadelta Trm cells and myeloid cells specifically near the sites of L. monocytogenes replication within the MLN to restrict bacterial growth and spread. Our findings support a role for gammadelta Trms in orchestrating protective immune responses against intestinal pathogens. PMID- 27402749 TI - Assessing large-scale wildlife responses to human infrastructure development. AB - Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future. PMID- 27402750 TI - Equity and length of lifespan are not the same. AB - Efforts to understand the dramatic declines in mortality over the past century have focused on life expectancy. However, understanding changes in disparity in age of death is important to understanding mechanisms of mortality improvement and devising policy to promote health equity. We derive a novel decomposition of variance in age of death, a measure of inequality, and apply it to cause-specific contributions to the change in variance among the G7 countries (Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States) from 1950 to 2010. We find that the causes of death that contributed most to declines in the variance are different from those that contributed most to increase in life expectancy; in particular, they affect mortality at younger ages. We also find that, for two leading causes of death [cancers and cardiovascular disease (CVD)], there are no consistent relationships between changes in life expectancy and variance either within countries over time or between countries. These results show that promoting health at younger ages is critical for health equity and that policies to control cancer and CVD may have differing implications for equity. PMID- 27402751 TI - The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution. AB - Developmental genetics research on mice provides a relatively sound understanding of the genes necessary and sufficient to make mammalian teeth. However, mouse dentitions are highly derived compared with human dentitions, complicating the application of these insights to human biology. We used quantitative genetic analyses of data from living nonhuman primates and extensive osteological and paleontological collections to refine our assessment of dental phenotypes so that they better represent how the underlying genetic mechanisms actually influence anatomical variation. We identify ratios that better characterize the output of two dental genetic patterning mechanisms for primate dentitions. These two newly defined phenotypes are heritable with no measurable pleiotropic effects. When we consider how these two phenotypes vary across neontological and paleontological datasets, we find that the major Middle Miocene taxonomic shift in primate diversity is characterized by a shift in these two genetic outputs. Our results build on the mouse model by combining quantitative genetics and paleontology, and thereby elucidate how genetic mechanisms likely underlie major events in primate evolution. PMID- 27402752 TI - Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature. AB - Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33-35 degrees C) than at lung temperature (37 degrees C). Recent studies found that although 37 degrees C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication at 37 degrees C, we studied RV infection in human bronchial epithelial cells and H1-HeLa cells. During the single replication cycle, RV exhibited temperature-dependent replication in both cell types in the absence of IFN induction. At 37 degrees C, earlier signs of apoptosis in RV-infected cells were accompanied by reduced virus production. Furthermore, apoptosis of epithelial cells was enhanced at 37 degrees C in response to diverse stimuli. Dynamic mathematical modeling and B cell lymphoma 2 (BCL2) overexpression revealed that temperature-dependent host cell death could partially account for the temperature-dependent growth observed during RV amplification, but also suggested additional mechanisms of virus control. In search of a redundant antiviral pathway, we identified a role for the RNA-degrading enzyme RNAseL. Simultaneous antagonism of apoptosis and RNAseL increased viral replication and dramatically reduced temperature dependence. These findings reveal two IFN-independent mechanisms active in innate defense against RV, and demonstrate that even in the absence of IFNs, temperature dependent RV amplification is largely a result of host cell antiviral restriction mechanisms operating more effectively at 37 degrees C than at 33 degrees C. PMID- 27402753 TI - Reversal of dendritic phenotypes in 16p11.2 microduplication mouse model neurons by pharmacological targeting of a network hub. AB - The architecture of dendritic arbors contributes to neuronal connectivity in the brain. Conversely, abnormalities in dendrites have been reported in multiple mental disorders and are thought to contribute to pathogenesis. Rare copy number variations (CNVs) are genetic alterations that are associated with a wide range of mental disorders and are highly penetrant. The 16p11.2 microduplication is one of the CNVs most strongly associated with schizophrenia and autism, spanning multiple genes possibly involved in synaptic neurotransmission. However, disease relevant cellular phenotypes of 16p11.2 microduplication and the driver gene(s) remain to be identified. We found increased dendritic arborization in isolated cortical pyramidal neurons from a mouse model of 16p11.2 duplication (dp/+). Network analysis identified MAPK3, which encodes ERK1 MAP kinase, as the most topologically important hub in protein-protein interaction networks within the 16p11.2 region and broader gene networks of schizophrenia-associated CNVs. Pharmacological targeting of ERK reversed dendritic alterations associated with dp/+ neurons, outlining a strategy for the analysis and reversal of cellular phenotypes in CNV-related psychiatric disorders. PMID- 27402755 TI - Helical arrays of U-shaped ATP synthase dimers form tubular cristae in ciliate mitochondria. AB - F1Fo-ATP synthases are universal energy-converting membrane protein complexes that synthesize ATP from ADP and inorganic phosphate. In mitochondria of yeast and mammals, the ATP synthase forms V-shaped dimers, which assemble into rows along the highly curved ridges of lamellar cristae. Using electron cryotomography and subtomogram averaging, we have determined the in situ structure and organization of the mitochondrial ATP synthase dimer of the ciliate Paramecium tetraurelia. The ATP synthase forms U-shaped dimers with parallel monomers. Each complex has a prominent intracrista domain, which links the c-ring of one monomer to the peripheral stalk of the other. Close interaction of intracrista domains in adjacent dimers results in the formation of helical ATP synthase dimer arrays, which differ from the loose dimer rows in all other organisms observed so far. The parameters of the helical arrays match those of the cristae tubes, suggesting the unique features of the P. tetraurelia ATP synthase are directly responsible for generating the helical tubular cristae. We conclude that despite major structural differences between ATP synthase dimers of ciliates and other eukaryotes, the formation of ATP synthase dimer rows is a universal feature of mitochondria and a fundamental determinant of cristae morphology. PMID- 27402754 TI - Decreased function of survival motor neuron protein impairs endocytic pathways. AB - Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN 1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death. PMID- 27402756 TI - Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation. AB - Mammalian target of rapamycin (mTOR)-directed eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation promotes cap-dependent translation and tumorigenesis. During mitosis, cyclin-dependent kinase 1 (CDK1) substitutes for mTOR and fully phosphorylates 4E-BP1 at canonical sites (T37, T46, S65, and T70) and the noncanonical S83 site, resulting in a mitosis-specific hyperphosphorylated delta isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. Although S83 phosphorylation of 4E-BP1 does not affect general cap-dependent translation, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus small T antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of delta-4E-BP1 may yield a gain of function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function. PMID- 27402757 TI - Single-cell analysis delineates a trajectory toward the human early otic lineage. AB - Efficient pluripotent stem cell guidance protocols for the production of human posterior cranial placodes such as the otic placode that gives rise to the inner ear do not exist. Here we use a systematic approach including defined monolayer culture, signaling modulation, and single-cell gene expression analysis to delineate a developmental trajectory for human otic lineage specification in vitro. We found that modulation of bone morphogenetic protein (BMP) and WNT signaling combined with FGF and retinoic acid treatments over the course of 18 days generates cell populations that develop chronological expression of marker genes of non-neural ectoderm, preplacodal ectoderm, and early otic lineage. Gene expression along this differentiation path is distinct from other lineages such as endoderm, mesendoderm, and neural ectoderm. Single-cell analysis exposed the heterogeneity of differentiating cells and allowed discrimination of non-neural ectoderm and otic lineage cells from off-target populations. Pseudotemporal ordering of human embryonic stem cell and induced pluripotent stem cell-derived single-cell gene expression profiles revealed an initially synchronous guidance toward non-neural ectoderm, followed by comparatively asynchronous occurrences of preplacodal and otic marker genes. Positive correlation of marker gene expression between both cell lines and resemblance to mouse embryonic day 10.5 otocyst cells implied reasonable robustness of the guidance protocol. Single-cell trajectory analysis further revealed that otic progenitor cell types are induced in monolayer cultures, but further development appears impeded, likely because of lack of a lineage-stabilizing microenvironment. Our results provide a framework for future exploration of stabilizing microenvironments for efficient differentiation of stem cell-generated human otic cell types. PMID- 27402758 TI - When genes and environment disagree: Making sense of trends in recent human evolution. PMID- 27402759 TI - FoxO3 regulates neuronal reprogramming of cells from postnatal and aging mice. AB - We and others have shown that embryonic and neonatal fibroblasts can be directly converted into induced neuronal (iN) cells with mature functional properties. Reprogramming of fibroblasts from adult and aged mice, however, has not yet been explored in detail. The ability to generate fully functional iN cells from aged organisms will be particularly important for in vitro modeling of diseases of old age. Here, we demonstrate production of functional iN cells from fibroblasts that were derived from mice close to the end of their lifespan. iN cells from aged mice had apparently normal active and passive neuronal membrane properties and formed abundant synaptic connections. The reprogramming efficiency gradually decreased with fibroblasts derived from embryonic and neonatal mice, but remained similar for fibroblasts from postnatal mice of all ages. Strikingly, overexpression of a transcription factor, forkhead box O3 (FoxO3), which is implicated in aging, blocked iN cell conversion of embryonic fibroblasts, whereas knockout or knockdown of FoxO3 increased the reprogramming efficiency of adult derived but not of embryonic fibroblasts and also enhanced functional maturation of resulting iN cells. Hence, FoxO3 has a central role in the neuronal reprogramming susceptibility of cells, and the importance of FoxO3 appears to change during development. PMID- 27402761 TI - How van der Waals interactions determine the unique properties of water. AB - Whereas the interactions between water molecules are dominated by strongly directional hydrogen bonds (HBs), it was recently proposed that relatively weak, isotropic van der Waals (vdW) forces are essential for understanding the properties of liquid water and ice. This insight was derived from ab initio computer simulations, which provide an unbiased description of water at the atomic level and yield information on the underlying molecular forces. However, the high computational cost of such simulations prevents the systematic investigation of the influence of vdW forces on the thermodynamic anomalies of water. Here, we develop efficient ab initio-quality neural network potentials and use them to demonstrate that vdW interactions are crucial for the formation of water's density maximum and its negative volume of melting. Both phenomena can be explained by the flexibility of the HB network, which is the result of a delicate balance of weak vdW forces, causing, e.g., a pronounced expansion of the second solvation shell upon cooling that induces the density maximum. PMID- 27402760 TI - AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption. AB - Filtration through the kidney eliminates toxins, manages electrolyte balance, and controls water homeostasis. Reabsorption of water from the luminal fluid of the nephron occurs through aquaporin-2 (AQP2) water pores in principal cells that line the kidney-collecting duct. This vital process is impeded by formation of an "actin barrier" that obstructs the passive transit of AQP2 to the plasma membrane. Bidirectional control of AQP2 trafficking is managed by hormones and signaling enzymes. We have discovered that vasopressin-independent facets of this homeostatic mechanism are under the control of A-Kinase Anchoring Protein 220 (AKAP220; product of the Akap11 gene). CRISPR/Cas9 gene editing and imaging approaches show that loss of AKAP220 disrupts apical actin networks in organoid cultures. Similar defects are evident in tissue sections from AKAP220-KO mice. Biochemical analysis of AKAP220-null kidney extracts detected reduced levels of active RhoA GTPase, a well-known modulator of the actin cytoskeleton. Fluorescent imaging of kidney sections from these genetically modified mice revealed that RhoA and AQP2 accumulate at the apical surface of the collecting duct. Consequently, these animals are unable to appropriately dilute urine in response to overhydration. We propose that membrane-proximal signaling complexes constrained by AKAP220 impact the actin barrier dynamics and AQP2 trafficking to ensure water homeostasis. PMID- 27402762 TI - Socially selected ornaments influence hormone titers of signalers and receivers. AB - Decades of behavioral endocrinology research have shown that hormones and behavior have a bidirectional relationship; hormones both influence and respond to social behavior. In contrast, hormones are often thought to have a unidirectional relationship with ornaments. Hormones influence ornament development, but little empirical work has tested how ornaments influence hormones throughout life. Here, we experimentally alter a visual signal of fighting ability in Polistes dominulus paper wasps and measure the behavioral and hormonal consequences of signal alteration in signalers and receivers. We find wasps that signal inaccurately high fighting ability receive more aggression than controls and receiving aggression reduces juvenile hormone (JH) titers. As a result, immediately after contests, inaccurate signalers have lower JH titers than controls. Ornaments also directly influence rival JH titers. Three hours after contests, wasps who interacted with rivals signaling high fighting ability have higher JH titers than wasps who interacted with rivals signaling low fighting ability. Therefore, ornaments influence hormone titers of both signalers and receivers. We demonstrate that relationships between hormones and ornaments are flexible and bidirectional rather than static and unidirectional. Dynamic relationships among ornaments, behavior, and physiology may be an important, but overlooked factor in the evolution of honest communication. PMID- 27402763 TI - p53-Dependent DNA damage response sensitive to editing-defective tRNA synthetase in zebrafish. AB - Brain and heart pathologies are caused by editing defects of transfer RNA (tRNA) synthetases, which preserve genetic code fidelity by removing incorrect amino acids misattached to tRNAs. To extend understanding of the broader impact of synthetase editing reactions on organismal homeostasis, and based on effects in bacteria ostensibly from small amounts of mistranslation of components of the replication apparatus, we investigated the sensitivity to editing of the vertebrate genome. We show here that in zebrafish embryos, transient overexpression of editing-defective valyl-tRNA synthetase (ValRS(ED)) activated DNA break-responsive H2AX and p53-responsive downstream proteins, such as cyclin dependent kinase (CDK) inhibitor p21, which promotes cell-cycle arrest at DNA damage checkpoints, and Gadd45 and p53R2, with pivotal roles in DNA repair. In contrast, the response of these proteins to expression of ValRS(ED) was abolished in p53-deficient fish. The p53-activated downstream signaling events correlated with suppression of abnormal morphological changes caused by the editing defect and, in adults, reversed a shortened life span (followed for 2 y). Conversely, with normal editing activities, p53-deficient fish have a normal life span and few morphological changes. Whole-fish deep sequencing showed genomic mutations associated with the editing defect. We suggest that the sensitivity of p53 to expression of an editing-defective tRNA synthetase has a critical role in promoting genome integrity and organismal homeostasis. PMID- 27402764 TI - Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria. AB - The genetic information in mammalian mitochondrial DNA is densely packed; there are no introns and only one sizeable noncoding, or control, region containing key cis-elements for its replication and expression. Many molecules of mitochondrial DNA bear a third strand of DNA, known as "7S DNA," which forms a displacement (D ) loop in the control region. Here we show that many other molecules contain RNA as a third strand. The RNA of these R-loops maps to the control region of the mitochondrial DNA and is complementary to 7S DNA. Ribonuclease H1 is essential for mitochondrial DNA replication; it degrades RNA hybridized to DNA, so the R loop is a potential substrate. In cells with a pathological variant of ribonuclease H1 associated with mitochondrial disease, R-loops are of low abundance, and there is mitochondrial DNA aggregation. These findings implicate ribonuclease H1 and RNA in the physical segregation of mitochondrial DNA, perturbation of which represents a previously unidentified disease mechanism. PMID- 27402765 TI - Blind tests of RNA nearest-neighbor energy prediction. AB - The predictive modeling and design of biologically active RNA molecules requires understanding the energetic balance among their basic components. Rapid developments in computer simulation promise increasingly accurate recovery of RNA's nearest-neighbor (NN) free-energy parameters, but these methods have not been tested in predictive trials or on nonstandard nucleotides. Here, we present, to our knowledge, the first such tests through a RECCES-Rosetta (reweighting of energy-function collection with conformational ensemble sampling in Rosetta) framework that rigorously models conformational entropy, predicts previously unmeasured NN parameters, and estimates these values' systematic uncertainties. RECCES-Rosetta recovers the 10 NN parameters for Watson-Crick stacked base pairs and 32 single-nucleotide dangling-end parameters with unprecedented accuracies: rmsd of 0.28 kcal/mol and 0.41 kcal/mol, respectively. For set-aside test sets, RECCES-Rosetta gives rmsd values of 0.32 kcal/mol on eight stacked pairs involving G-U wobble pairs and 0.99 kcal/mol on seven stacked pairs involving nonstandard isocytidine-isoguanosine pairs. To more rigorously assess RECCES Rosetta, we carried out four blind predictions for stacked pairs involving 2,6 diaminopurine-U pairs, which achieved 0.64 kcal/mol rmsd accuracy when tested by subsequent experiments. Overall, these results establish that computational methods can now blindly predict energetics of basic RNA motifs, including chemically modified variants, with consistently better than 1 kcal/mol accuracy. Systematic tests indicate that resolving the remaining discrepancies will require energy function improvements beyond simply reweighting component terms, and we propose further blind trials to test such efforts. PMID- 27402766 TI - Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS. AB - Endothelial cells (ECs) are critical mediators of blood pressure (BP) regulation, primarily via the generation and release of vasorelaxants, including nitric oxide (NO). NO is produced in ECs by endothelial NO synthase (eNOS), which is activated by both calcium (Ca(2+))-dependent and independent pathways. Here, we report that intracellular Ca(2+) release from the endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptor (IP3R) is required for Ca(2+)-dependent eNOS activation. EC-specific type 1 1,4,5-trisphosphate receptor knockout (IP3R1(-/-)) mice are hypertensive and display blunted vasodilation in response to acetylcholine (ACh). Moreover, eNOS activity is reduced in both isolated IP3R1 deficient murine ECs and human ECs following IP3R1 knockdown. IP3R1 is upstream of calcineurin, a Ca(2+)/calmodulin-activated serine/threonine protein phosphatase. We show here that the calcineurin/nuclear factor of activated T cells (NFAT) pathway is less active and eNOS levels are decreased in IP3R1 deficient ECs. Furthermore, the calcineurin inhibitor cyclosporin A, whose use has been associated with the development of hypertension, reduces eNOS activity and vasodilation following ACh stimulation. Our results demonstrate that IP3R1 plays a crucial role in the EC-mediated vasorelaxation and the maintenance of normal BP. PMID- 27402767 TI - Astrocytic beta2-adrenergic receptors mediate hippocampal long-term memory consolidation. AB - Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which beta2-adrenergic receptors (betaARs) are of particular importance. The differential anatomical and cellular distribution of betaAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal beta2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal beta2ARs, but not beta1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long-term memory formation and for underlying molecular changes. This key metabolic role of astrocytic beta2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration. PMID- 27402768 TI - Growing timescales and lengthscales characterizing vibrations of amorphous solids. AB - Low-temperature properties of crystalline solids can be understood using harmonic perturbations around a perfect lattice, as in Debye's theory. Low-temperature properties of amorphous solids, however, strongly depart from such descriptions, displaying enhanced transport, activated slow dynamics across energy barriers, excess vibrational modes with respect to Debye's theory (i.e., a boson peak), and complex irreversible responses to small mechanical deformations. These experimental observations indirectly suggest that the dynamics of amorphous solids becomes anomalous at low temperatures. Here, we present direct numerical evidence that vibrations change nature at a well-defined location deep inside the glass phase of a simple glass former. We provide a real-space description of this transition and of the rapidly growing time- and lengthscales that accompany it. Our results provide the seed for a universal understanding of low-temperature glass anomalies within the theoretical framework of the recently discovered Gardner phase transition. PMID- 27402770 TI - Reductions in Alcohol Craving Following Naltrexone Treatment for Heavy Drinking. AB - AIMS: The role of craving for alcohol as a response to alcohol treatment is not well understood. We examined daily diary ratings of craving over the course of 28 days among individuals participating in an inpatient substance abuse treatment program. METHODS: Participants were alcohol dependent patients (n = 100) in the Hazelden residential treatment program who were offered and agreed to take naltrexone and an age- and gender-matched comparison group (n = 100) of alcohol dependent patients in the same program who declined the offer of treatment with naltrexone. Changes in craving over time were compared between the two groups. RESULTS: The naltrexone-treated group reported a more rapid decrease in craving than the usual care group. CONCLUSIONS: The change in the trajectory of craving is consistent with prior reports suggesting that craving reduction is a mechanism of naltrexone's efficacy in treating alcohol dependence. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in their craving, consistent with a primary target of many addiction treatment programs. SHORT SUMMARY: Craving ratings by 100 residential patients taking naltrexone for alcohol dependence were compared to ratings by 100 patients who did not take naltrexone. Craving for alcohol decreased more rapidly in the patients taking naltrexone. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in craving, which may benefit treatment efforts. PMID- 27402769 TI - Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion. AB - We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a consequence of impaired production of nucleotides needed for DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all four nucleotide triphosphates, whereas inhibition of the protein kinase AKT is less effective than inhibition of PI3K in suppressing nucleotide synthesis and inducing DNA damage. Carbon flux studies reveal that PI3K inhibition disproportionately affects the nonoxidative pentose phosphate pathway that delivers Rib-5-phosphate required for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative breast cancer (K14-Cre BRCA1(f/f)p53(f/f)), the PI3K inhibitor BKM120 led to a precipitous drop in DNA synthesis within 8 h of drug treatment, whereas DNA synthesis in normal tissues was less affected. In this mouse model, combined PI3K and PARP inhibition was superior to either agent alone to induce durable remissions of established tumors. PMID- 27402772 TI - Erratum: MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. PMID- 27402771 TI - A historiographic study of psychiatric treatments in Brazil: mentalism and organicism from 1830 to 1859. AB - Our aim is to investigate two major tendencies in nineteenth-century Brazilian alienism: mentalism and organicism, by conducting a descriptive study of original Brazilian documents on medical health treatments in the 1830s, 1840s and 1850s. Primary sources of Brazilian alienism were theses, memoirs, official reports, and documents written by clinicians and asylum directors. We analysed early mental treatment in Brazilian lunatic asylums, exploring the relative contributions of two main theoretical orientations: moral treatment (based on Pinel and Esquirol) and 'medical-organicist therapeutic orientation'. Intertextuality was used to assess reports of medical organicist treatment in Brazil. We concluded that contemporaneous textual sources indicate that mid-nineteenth-century alienism in Brazil was predominantly influenced by organicism exported from European countries. Pinel's mentalist view, nevertheless, remained the reference point for clinical issues associated with the doctor-patient relationship. PMID- 27402773 TI - Erratum: Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis. PMID- 27402774 TI - Validity of Self-Reported Medication Use Compared With Pharmacy Records in a Cohort of Older Women: Findings From the Women's Health Initiative. AB - Inaccurate self-reported data on medication exposure lead to less reliable study findings. From 2013 to 2015, we assessed the validity of information on medication use collected via a mailed medication inventory among 223 Women's Health Initiative participants who were members of a health-care delivery system. Self-reported information on medication use was compared with pharmacy records for statins, calcium channel blockers, beta-blockers, and bisphosphonates. We assessed sensitivity, specificity, and positive predictive value (PPV) for current medication use. We assessed agreement on duration of use (<2, 2, 3, 4, or >=5 years) by means of the weighted kappa statistic. The mean age of participants was 77 years. Statins, beta-blockers, and calcium channel blockers were each reported by over 15% of women, and bisphosphonates were reported by 4.5%. Compared with pharmacy records, the sensitivity, specificity, and PPV for self reported use of statins, beta-blockers, and calcium channel blockers were all 95% or greater. The sensitivity and PPV for bisphosphonate use were both 80% (95% confidence interval: 44, 97), and specificity was 99% (95% confidence interval: 97, 100). The kappa statistic for duration of use was 0.87 or greater for all 4 medication classes. Compared with pharmacy records, self-reported information on current medication use and duration of use collected via mailed medication inventory among older women had almost perfect agreement for use of statins, beta blockers, and calcium channel blockers. PMID- 27402775 TI - The First Cut Is the Deepest: The History and Development of Safe Treatments for Wound Healing and Tissue Repair. AB - As the skin is the primary barrier to infection, the importance of wound healing has been understood since ancient times. This article provides a synopsis on the symposium presentations focusing on how wounds were traditionally treated, what models and pathology endpoints exist to study wound healing, special considerations for wound healing studies, an overview of regulatory aspects of new pharmaceutical and medical device development, and the clinical relevance of such models. The clinical treatment of small and large wounds is also considered. PMID- 27402776 TI - Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology, and Survival in the Mouse Model of Bubonic Plague. AB - BACKGROUND: Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague. METHODS: Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-Y. pestis antibodies alone or in combination with the corticosteroid methylprednisolone. RESULTS: The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase 9 in the tissues, and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs. CONCLUSIONS: Corticosteroids induce an unexpectedly effective antibacterial response apart from their antiinflammatory properties, thereby improving treatment efficacy. PMID- 27402777 TI - Ockham's Razor and the PrePex Male Circumcision Device. PMID- 27402778 TI - Genital Anaerobic Bacterial Overgrowth and the PrePex Male Circumcision Device, Rakai, Uganda. PMID- 27402780 TI - Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa. AB - BACKGROUND: As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. METHODS: HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, >=400 cps/mL) using Cox models. If VL was >=1000 cps/mL, genotyping was performed. RESULTS: Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs >=400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40-14.83; P < .001) or PI-based (7.59; 3.02-19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P < .001), and suboptimal adherence (3.05; 1.71-5.42; P = .025). Among participants with VLs >=1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. CONCLUSIONS: Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs >=1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary. PMID- 27402781 TI - Penetration barrier contributes to bacterial biofilm-associated resistance against only select antibiotics, and exhibits genus-, strain- and antibiotic specific differences. AB - Bacterial biofilms are implicated in a wide range of implant-based and chronic infections. These infections are often associated with adverse therapeutic outcomes, owing to the decreased antibiotic susceptibility of biofilms compared with their planktonic counterparts. This altered biofilm susceptibility has been attributed to multiple factors, including a reduced antibiotic penetration. Although several studies have addressed the role of penetration barrier in biofilm-associated drug resistance, it remains inconclusive. This study was done to elucidate antibiotic penetration through biofilms formed by Staphylococcus aureus, S. epidermidis, Escherichia coli and Klebsiella pneumoniae, using an agar disk diffusion assay. Penetration capacity of six antimicrobial drugs from different classes (beta-lactams, aminoglycosides, tetracyclines, phenicols, fluoroquinolones and glycopeptides) through biofilms formed by standard strains and clinical isolates from catheter-related bloodstream infections (CRBSI) was elucidated by measuring their growth-inhibition zones in lawn cultures on Mueller Hinton agar, following diffusion of an antibiotic from an overlying disk through their biofilm to the agar medium. Penetration of only select antimicrobials (vancomycin and chloramphenicol) was hindered through biofilms. There was considerable variation in biofilm-permeating capacity depending upon the genus, strain/CRBSI isolate and antibiotic tested. Furthermore, antibiotics failed to kill the biofilm cells independent of penetration, indicating that other factors contributed substantially to biofilm resistance. PMID- 27402782 TI - Identification of a virulence determinant that is conserved in the Jawetz and Heyl biotypes of [Pasteurella] pneumotropica. AB - [Pasteurella] pneumotropica is a ubiquitous bacterium frequently isolated from laboratory rodents. Although this bacterium causes various diseases in immunosuppressed animals, little is known about major virulence factors and their roles in pathogenicity. To identify virulence factors, we sequenced the genome of [P.] pneumotropica biotype Heyl strain ATCC 12555, and compared the resulting non contiguous draft genome sequence with the genome of biotype Jawetz strain ATCC 35149. Among a large number of genes encoding virulence-associated factors in both strains, four genes encoding for YadA-like proteins, which are known virulence factors that function in host cell adherence and invasion in many pathogens. In this study, we assessed YadA distribution and biological activity as an example of one of virulence-associated factor shared, with biotype Jawetz and Heyl. More than half of mouse isolates were found to have at least one of these genes; whereas, the majority of rat isolates did not. Autoagglutination activity, and ability to bind to mouse collagen type IV and mouse fibroblast cells, was significantly higher in YadA-positive than YadA-negative strains. To conclude, we identified a large number of candidate genes predicted to influence [P.] pneumotropica pathogenesis. PMID- 27402779 TI - An Outbreak of Ebola Virus Disease in the Lassa Fever Zone. AB - BACKGROUND: Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs. METHODS: Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities. RESULTS: Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case. CONCLUSIONS: Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources. PMID- 27402785 TI - Editorial: The complexity of microbial biofilm research-an introduction to the third thematic issue on biofilms. PMID- 27402784 TI - Detection of intracellular bacteria in exfoliated urothelial cells from women with urge incontinence. AB - The role of subclinical infection in patients with urge incontinence has been largely ignored. The aim of this study was to test for the presence of intracellular bacteria in exfoliated urothelial cells obtained from the urine of patients with detrusor overactivity or mixed incontinence +/- a history of UTI, and compare this to a control group of patients with stress incontinence and no history of infection. Bacterial cystitis was assessed by routine microbiology and compared to microscopic analysis of urine by Wright staining. Subsequent analysis of urothelial cells by confocal microscopy was performed to determine the existence of intracellular bacteria. Bacterial cystitis was seen in 13% of patients based on routine microbiology. Wright staining of concentrated urothelial cells demonstrated the presence of bacteria in 72% of samples. Filamentous bacterial cells were observed in 51% of patients and were significantly more common in patients with detrusor overactivity. Intracellular Escherichia coli were observed by confocal microscopy. This study supports the possibility that a subset of patients with urge incontinence may have unrecognised chronic bacterial colonisation, maintained via an intracellular reservoir. In patients with negative routine microbiology, application of the techniques used in this study revealed evidence of infection, providing further insights into the aetiology of urge incontinence. PMID- 27402786 TI - The Impact of Aesthetic Surgery on Body Image and its Implications for Mental and Physical Health. PMID- 27402783 TI - Macrophage form, function, and phenotype in mycobacterial infection: lessons from tuberculosis and other diseases. AB - Macrophages play a central role in mycobacterial pathogenesis. Recent work has highlighted the importance of diverse macrophage types and phenotypes that depend on local environment and developmental origins. In this review, we highlight how distinct macrophage phenotypes may influence disease progression in tuberculosis. In addition, we draw on work investigating specialized macrophage populations important in cancer biology and atherosclerosis in order to suggest new areas of investigation relevant to mycobacterial pathogenesis. Understanding the mechanisms controlling the repertoire of macrophage phenotypes and behaviors during infection may provide opportunities for novel control of disease through modulation of macrophage form and function. PMID- 27402787 TI - Influence of the Pectoralis Major Muscle Sling in Chest Wall-Based Flap Suspension After Vertical Mammaplasty: Ten-Year Follow-Up. AB - BACKGROUND: The pectoralis muscle sling has proven to be a suitable alternative technique for long-term results in breast parenchyma suspension. Although the pectoralis muscle sling has been subjectively observed to reduce the bottoming out effect with a bipedicled muscle flap (muscular loop), there has not been a study to objectively or numerically prove it. OBJECTIVES: This study aimed to radiologically evaluate the influence of a pectoralis muscle sling in supporting the chest wall-based flap after a vertical breast-reduction technique. METHODS: Twenty-one female patients underwent a vertical breast reduction with the chest wall-based flap and were randomly divided into two subgroups. Ten patients were in subgroup (S), which consisted of patients with a muscle sling. Eleven patients without the muscle sling technique were assigned as a control group (C). Periodic radiological examinations were performed at 1, 3, 6, and 12 months and then at 10 years postoperatively to analyze the breast flap and any migration with respect to three titanium clips placed intraoperatively on the chest wall parenchyma flap. RESULTS: Patients in subgroup S had a significantly higher difference in migration of the chest wall-based flaps between the first day and 10 years postoperatively when compared with patients in subgroup C (P < .001), as shown by the distances measured between titanium clip locations. CONCLUSIONS: After 10 years of follow-up, there were changes in chest wall-based flap bottoming-out in patients in whom a pectoralis major muscle sling was utilized compared with those patients without it. Thus, a pectoralis major muscle sling seems to provide greater and longer-lasting support to the flap position on the patient's chest. LEVEL OF EVIDENCE: 2 Therapeutic. PMID- 27402788 TI - Are There Factors Predictive of Postoperative Complications in Circumferential Contouring of the Lower Trunk? A Meta-Analysis. AB - BACKGROUND: The massive weight loss patient may require a circumferential contouring of the lower trunk. OBJECTIVES: To summarize the complication rates and explore the possibility of predictive risk factors for complications. METHODS: We performed a systematic review using the PubMed and Cochrane databases to identify published articles on the topic. Random effects meta-analyses and meta-regression were conducted to synthesize the data gathered. RESULTS: The analysis included 28 studies and 1380 patients. All but one were retrospective cohorts or case studies. Circumferential contouring of the lower trunk resulted in 37% [95%-CI 30%; 44%] overall complications; 17% [95%-CI 12%; 24%] wound dehiscences; 4% [95%-CI 3%; 5%] skin necrosis; 5% [95%-CI 3%; 9%] infections; 3% [95%-CI 2%; 4%] hematomas; 13% [95%-CI 9%; 18%] seromas; 12% [95%-CI 7%; 21%] scar irregularities; 3% [95%-CI 2%; 5%] thromboembolism; and 5% [95%-CI 3%; 8%] revisions for complications. Lower body lift-related techniques were associated with a higher rate of overall complications than belt lipectomy-related techniques (P = .002). No difference in complication rate was shown when performing a gluteal augmentation with flap. Due to insufficient data reported in the studies, risk factors for postoperative complications could not be assessed. CONCLUSIONS: The whole literature provides very low reliable information. Confusion factors could not be ruled out to explain the increased complications rate for the lower body lift compared to the belt lipectomy. This finding needs to be confirmed in randomized trials. Collaborative efforts must be made to improve the evidence level of our practices and to serve patients in an optimal way. LEVEL OF EVIDENCE: 3 Therapeutic. PMID- 27402789 TI - Promoting health by addressing living conditions in Norwegian municipalities. AB - Worldwide, inequalities in health are increasing, even in well-developed welfare states such as Norway, which in 2012, saw a new public health act take effect that enshrined equity in health as national policy and devolved to municipalities' responsibility to act on the social determinants of health. The act deems governance structures and "Health in All Policies" approaches as important steering mechanisms for local health promotion. The aim of this study is to investigate whether Norway's municipalities address living conditions - economic circumstances, housing, employment and educational factors - in local health promotion, and what factors are associated with doing so. All Norway's municipalities (n= 428) were included in this cross-sectional study, and both register and survey data were used and were subjected to descriptive and bi- and multivariate regression analyses. Eighty-two percent of the municipalities reported that they were capable of reducing inequalities in health. Forty percent of the municipalities defined living conditions as a main challenge in their local public health promotion, while 48% cited it as a main health promotion priority. Our study shows that defining living conditions as a main challenge is positively associated with size of municipality, and also its assessment of its own capability in reducing inequalities in health. The latter factor was also associated with actually prioritizing living conditions in health promotion, as was having established cross-sectorial working groups or inter-municipal collaboration related to local health promotion. This study underlines the importance of inter-sectoral collaboration to promote health and well-being. PMID- 27402790 TI - Food environment and policies in private schools in Kolkata, India. AB - School food policies and services have the potential to influence the food practices and eating behaviours of adolescents which in turn may affect their lifestyles and health in adulthood. The aim of this qualitative investigation was to describe the opinions of adolescents, their parents, nutrition educators and school principals about the prevailing food environment and canteen policies in Indian schools. Fifteen adolescents aged 14-15 years, 15 parents, 12 teachers and 10 principals from 10 private schools in Kolkata, India participated in semi structured interviews. The interview questions were primarily based on the existing literature related to school food environments and policies. Audio recordings were transcribed verbatim and assessed thematically. Throughout the 52 interviews, a number of inadequacies of the school food environment and policies were revealed. These included the absence of written food policies, the widespread supply of unhealthy foods, inadequate provision of healthy foods, misleading messages about food communicated by school authorities, lack of cleanliness in the school canteen and the high cost of canteen food. Current school food environments do not appear to promote healthy eating among adolescents. Therefore, it is important to upgrade the quality of food services in Indian schools through adoption of healthy eating policies. PMID- 27402791 TI - Near Infrared Imaging As a Method of Studying Tsetse Fly (Diptera: Glossinidae) Pupal Development. AB - Near infrared (NIR) photography and video was investigated as a method for observing and recording intrapuparial development in the tsetse fly Glossina palpalis gambiensis and other Muscomorpha (Cyclorrhapha) Diptera. We showed that NIR light passes through the puparium, permitting images of the true pupae and pharate adult to be captured. Various wavelengths of NIR light from 880 to 1060 nm were compared to study the development of tsetse fly pupae from larviposition to emergence, using time-lapse videos and photographs. This study was carried out to advance our understanding of tsetse pupal development, specifically with the goal of improving a sorting technique which could separate male from female tsetse flies several days before emergence. Separation of the sexes at this stage is highly desirable for operational tsetse sterile insect technique control programmes, as it would permit the easy retention of females for the colony while allowing the males to be handled, irradiated and shipped in the pupal stage when they are less sensitive to vibration. In addition, it presents a new methodology for studying the pupal stage of many coarctate insects for many applications. NIR imaging permits observation of living pupae, allowing the entire development process to be observed without disruption. PMID- 27402793 TI - In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport. AB - The transport of cytosolic adenosine diphosphate (ADP) into the mitochondria is a major control point in metabolic homeostasis, as ADP concentrations directly affect glycolytic flux and oxidative phosphorylation rates within mitochondria. A large contributor to the efficiency of this process is thought to involve phosphocreatine (PCr)/Creatine (Cr) shuttling through mitochondrial creatine kinase (Mi-CK), whereas the biological importance of alterations in Cr independent ADP transport during exercise remains unknown. Therefore, we utilized an Mi-CK knockout (KO) model to determine whether in vivo Cr-independent mechanisms are biologically important for sustaining energy homeostasis during exercise. Ablating Mi-CK did not alter exercise tolerance, as the time to volitional fatigue was similar between wild-type (WT) and KO mice at various exercise intensities. In addition, skeletal muscle metabolic profiles after exercise, including glycogen, PCr/Cr ratios, free ADP/adenosine monophosphate (AMP), and lactate, were similar between genotypes. While these data suggest that the absence of PCr/Cr shuttling is not detrimental to maintaining energy homeostasis during exercise, KO mice displayed a dramatic increase in Cr independent mitochondrial ADP sensitivity after exercise. Specifically, whereas mitochondrial ADP sensitivity decreased with exercise in WT mice, in stark contrast, exercise increased mitochondrial Cr-independent ADP sensitivity in KO mice. As a result, the apparent ADP Km was 50% lower in KO mice after exercise, suggesting that in vivo activation of voltage-dependent anion channel (VDAC)/adenine nucleotide translocase (ANT) can support mitochondrial ADP transport. Altogether, we provide insight that Cr-independent ADP transport mechanisms are biologically important for regulating ADP sensitivity during exercise, while highlighting complex regulation and the plasticity of the VDAC/ANT axis to support adenosine triphosphate demand. PMID- 27402792 TI - Graphics processing units in bioinformatics, computational biology and systems biology. AB - Several studies in Bioinformatics, Computational Biology and Systems Biology rely on the definition of physico-chemical or mathematical models of biological systems at different scales and levels of complexity, ranging from the interaction of atoms in single molecules up to genome-wide interaction networks. Traditional computational methods and software tools developed in these research fields share a common trait: they can be computationally demanding on Central Processing Units (CPUs), therefore limiting their applicability in many circumstances. To overcome this issue, general-purpose Graphics Processing Units (GPUs) are gaining an increasing attention by the scientific community, as they can considerably reduce the running time required by standard CPU-based software, and allow more intensive investigations of biological systems. In this review, we present a collection of GPU tools recently developed to perform computational analyses in life science disciplines, emphasizing the advantages and the drawbacks in the use of these parallel architectures. The complete list of GPU powered tools here reviewed is available at http://bit.ly/gputools. PMID- 27402794 TI - Structural and biophysical analysis of nuclease protein antibiotics. AB - Protein antibiotics (bacteriocins) are a large and diverse family of multidomain toxins that kill specific Gram-negative bacteria during intraspecies competition for resources. Our understanding of the mechanism of import of such potent toxins has increased significantly in recent years, especially with the reporting of several structures of bacteriocin domains. Less well understood is the structural biochemistry of intact bacteriocins and how these compare across bacterial species. Here, we focus on endonuclease (DNase) bacteriocins that target the genomes of Escherichia coli and Pseudomonas aeruginosa, known as E-type colicins and S-type pyocins, respectively, bound to their specific immunity (Im) proteins. First, we report the 3.2 A structure of the DNase colicin ColE9 in complex with its ultra-high affinity Im protein, Im9. In contrast with Im3, which when bound to the ribonuclease domain of the homologous colicin ColE3 makes contact with the translocation (T) domain of the toxin, we find that Im9 makes no such contact and only interactions with the ColE9 cytotoxic domain are observed. Second, we report small-angle X-ray scattering data for two S-type DNase pyocins, S2 and AP41, into which are fitted recently determined X-ray structures for isolated domains. We find that DNase pyocins and colicins are both highly elongated molecules, even though the order of their constituent domains differs. We discuss the implications of these architectural similarities and differences in the context of the translocation mechanism of protein antibiotics through the cell envelope of Gram-negative bacteria. PMID- 27402795 TI - Isoform-specific function of calpains in cell adhesion disruption: studies in postlactational mammary gland and breast cancer. AB - Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca(2+)-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, beta-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able to cleave adhesion proteins from lactating mammary gland in vitro Nevertheless, CAPN2 was the only isoform found to co-localize with E-cadherin in cell junctions at the peak of lactation. CAPN2/E-cadherin in vivo interaction, analyzed by proximity ligation assay, was dramatically increased during involution. Calpain inhibitor administration prevented the cytosolic accumulation of truncated E cadherin cleaved by CAPN2. Conversely, in breast cancer cells, CAPN2 was restricted to the nuclear compartment. The isoform-specific expression of CAPNs and CAPN activity was dependent on the breast cancer subtype. However, CAPN1 and CAPN2 knockdown cells showed that cleavage of adhesion proteins and cell migration was mediated by CAPN1, independently of the breast cancer cell line used. Data presented here suggest that the subcellular distribution of CAPN1 and CAPN2 is a major issue in target-substrate recognition; therefore, it determines the isoform-specific role of CAPNs during disruption of cell adhesion in either a physiological or a pathological context. PMID- 27402797 TI - Impact of the oncogenic status on the mode of recurrence in resected non-small cell lung cancer. AB - OBJECTIVE: Surgical resection is employed in patients with resectable non-small cell lung cancer. Despite complete resection, recurrence is sometimes observed. Oncogenic mutations promote initiation and progression of lung cancer, and mutation status predicts treatment outcome of advanced non-small cell lung cancer; however, their impact on the recurrence patterns remains poorly understood. METHODS: We retrospectively studied 401 patients showing recurrence after complete resection of non-small cell lung cancer. Clinicopathological factors were reviewed for time to recurrence, and recurrence patterns were compared according to oncogenic status and examined according to EGFR mutational subtype. RESULTS: Among 401 patients, 185 with EGFR mutation, 46 with KRAS mutation, 15 with ALK rearrangement and 155 with triple-negative mutation were identified. Multivariate analysis following univariate analyses showed that younger age, well-moderately-differentiated histology, earlier pathologic stage and presence of EGFR or ALK mutation were favorable prognostic factors for time to recurrence. Locoregional recurrence was observed in 53.3% of ALK-positive patients, being significantly common in these patients than in EGFR- and KRAS positive patients. EGFR-positive patients mostly experienced pleural recurrence, the incidence of which was significantly higher in triple-negative mutation patients. Adrenal recurrence was observed in 7.2% of triple-negative mutation patients, but it was rarely identified in EGFR-positive patients. Among EGFR positive patients, the incidence of brain metastases was significantly higher in L858R cohort than in Del Ex19 cohort. CONCLUSIONS: In resected non-small cell lung cancer, younger age, well-moderately-differentiated histology, earlier pathologic stage and presence of EGFR or ALK mutation were favorable factors for TTR, and distinct recurrence patterns were revealed according to oncogenic mutation status and mutational EGFR subtype. Our results may provide suggestions for developing a strategy for follow-up and adjuvant therapies after resection. PMID- 27402796 TI - TLR and TNF-R1 activation of the MKK3/MKK6-p38alpha axis in macrophages is mediated by TPL-2 kinase. AB - Previous studies suggested that Toll-like receptor (TLR) stimulation of the p38alpha MAP kinase (MAPK) is mediated by transforming growth factor-beta activated kinase 1 (TAK1) activation of MAPK kinases, MKK3, MKK4 and MKK6. We used quantitative mass spectrometry to monitor tumour progression locus 2 (TPL-2) dependent protein phosphorylation following TLR4 stimulation with lipopolysaccharide, comparing macrophages from wild-type mice and Map3k8(D270A/D270A) mice expressing catalytically inactive TPL-2 (MAP3K8). In addition to the established TPL-2 substrates MKK1/2, TPL-2 kinase activity was required to phosphorylate the activation loops of MKK3/6, but not of MKK4. MKK3/6 activation required IkappaB kinase (IKK) phosphorylation of the TPL-2 binding partner nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappaB1) p105, similar to MKK1/2 activation. Tumour necrosis factor (TNF) stimulation of MKK3/6 phosphorylation was similarly dependent on TPL-2 catalytic activity and IKK phosphorylation of NF-kappaB1 p105. Owing to redundancy of MKK3/6 with MKK4, Map3k8(D270A) mutation only fractionally decreased lipopolysaccharide activation of p38alpha. TNF activation of p38alpha, which is mediated predominantly via MKK3/6, was substantially reduced. TPL-2 catalytic activity was also required for MKK3/6 and p38alpha activation following macrophage stimulation with Mycobacterium tuberculosis and Listeria monocytogenes Our experiments demonstrate that the IKK/NF-kappaB1 p105/TPL-2 signalling pathway, downstream of TAK1, regulates MKK3/6 and p38alpha activation in macrophages in inflammation. PMID- 27402798 TI - Transarterial Onyx embolization of jugular foramen dural arteriovenous fistula with spinal venous drainage manifesting as myelopathy-a case report and review of the literature. AB - We report a rare case of jugular foramen dural arteriovenous fistula (DAVF) with spinal venous drainage. A 48-year-old woman suffered from progressive weakness of lower extremities and incontinence of urine and feces for 14 days. Magnetic resonance imaging (MRI) revealed a tortuous posterior medullary vein at C2-T2 and ischemic signal at C2-C4 of the spinal cord. Brain MRI revealed an abnormal high signal near the left jugular foramen. Digital subtraction angiography of the spinal vascular was negative, while brain angiography showed a left jugular foramen DAVF with spinal perimedullary venous drainage. The patient recovered completely soon after endovascular embolization with Onyx-18. Diagnosis of a DAVF presenting with myelopathy is challenging. Early diagnosis and treatment are essential for a favorable outcome. PMID- 27402799 TI - Two-stage reconstructive overlapping stent LEO+ and SILK for treatment of intracranial circumferential fusiform aneurysms in the posterior circulation. AB - Intracranial circumferential fusiform aneurysms of the posterior circulation involving arterial branches or perforating vessels are difficult to treat. This article shows an endovascular reconstruction technique not yet described, using a telescoping self-expandable stent (LEO+) and flow-diverter device (SILK) at different surgical times. Two patients with circumferential fusiform aneurysm, one being an aneurysm of the segments P2 and P3 of the posterior cerebral artery, diagnosed after a headache, and the other a partially thrombosed aneurysm of the lower basilar artery, diagnosed following ischemia of the brain stem. Endovascular treatment was performed by means of a vascular reconstruction technique that used at different surgical times: overlapping; a telescoped self expandable stent, LEO+; and a flow-diverter device, SILK. Angiographic control was carried out at 6 and 12 months, to evaluate arterial patency, flow maintenance in the arterial branches and perforating vessels, and thrombosis of the aneurysm. The combined use at different surgical times of the self-expandable stent and flow-diverter device was technically successful in both patients. There were no complications during the procedure, nor in the long-term follow-up with full arterial vascular reconstruction, maintenance of cerebral perfusion and complete aneurysm occlusion at the 6- and 12-month angiographic follow-up. There was no aneurysm recanalization nor intra-stent stenosis. Circumferential fusiform aneurysm of the posterior circulation involving arterial branches or perforating vessels to the brain stem may be treated with this arterial reconstruction technique at different surgical times, using the self-expandable stent called LEO+ and the flow-diverter device SILK, minimizing the risk of complications and failure of the endovascular technique, with the potential for arterial reconstruction with thrombosis of the aneurysmatic sac, as well as flow maintenance in the eloquent arteries, in this type of cerebral aneurysm. PMID- 27402800 TI - Role of endovascular embolization for trigeminal neuralgia related to cerebral vascular malformation. AB - OBJECTIVE: The objective of this article is to describe the trigeminal neuralgia related to cerebral vascular malformation that is rarely reported and the experience referring to endovascular treatment. PATIENTS AND METHODS: A total of 10 patients who had cerebral vascular malformation (AVM and dAVF) in a single center presented with trigeminal neuralgia. Clinical and angiographic presentations as well as their clinical outcomes after embolization were reviewed. RESULTS: Of the 10 cases, seven dAVFs and three AVMs were detected. In contrast to the dilated feeding arteries, an ectasia of the draining vein that is adjacent to the root entry zone of the trigeminal nerve such as the petrosal vein and lateral mesencephalic vein has the major role in causing the trigeminal neuralgia. All of these patients had relief of facial pain after endovascular embolization during follow-up (mean 57.3 months, range 5 to 100 months). There were no permanent neurological deficits. CONCLUSIONS: Endovascular embolization is an effective method in treating trigeminal neuralgia related to cerebral vascular malformation. PMID- 27402803 TI - Direct oral anticoagulants: unique properties and practical approaches to management. AB - Since 2009, four direct oral anticoagulants (DOACs) have been introduced for treatment of venous thromboembolism and stroke prevention in non-valvular atrial fibrillation. While they are currently first-line therapy for a majority of patients, there are a number of clinical situations where warfarin is preferable. In both randomised trials and real-world populations, use of DOACs significantly reduces the risk of intracranial haemorrhage as compared with warfarin. While drug-specific reversal agents are currently only available for dabigatran, andexanet alpha is pending approval for reversal of factor Xa inhibitors, reducing concerns about major bleeding for many patients and providers. DOACs can be held for 2-4 days prior to a procedure, depending on a patient's renal function, but should not be restarted too rapidly post-procedurally given their fast time to peak activity (~2 hours). The anticoagulation clinic should play an important role in managing patients on all oral anticoagulation, both warfarin and DOACs. PMID- 27402802 TI - Niemann-Pick type C2 deficiency impairs autophagy-lysosomal activity, mitochondrial function, and TLR signaling in adipocytes. AB - In this study, we investigated the role and mechanism of Niemann-Pick type C (NPC)2 in regulating lysosomal activity, mitophagy, and mitochondrial function in adipocytes. We found that knocking down NPC2 impaired lysosomal activity, as evidenced by the reduced mature cathepsin B, the increased accumulation of light chain 3 (LC3) and p62, and the decreased autophagic flux. In NPC2-knockdown (kd) adipocytes, the starvation-induced conversion of LC3-I to LC3-II was abolished. More interestingly, the majority of NPC2 was found in the mitochondrial fraction, and NPC2 deficiency led to impaired autophagic flux and decreased induction of LC3-II in the mitochondrial fraction during mitochondrial stress. Moreover, cellular respiration profiling revealed that NPC2-kd adipocytes had significantly decreased basal/maximal respiration and mitochondrial gene expression compared with scrambled cells, suggesting mitochondrial dysfunction. Additionally, we found that the mitochondrial recruitment of LC3-II induced by lipopolysaccharide (LPS), but not TNFalpha, was blunted in NPC2-kd adipocytes. Most intriguingly, NPC2-kd selectively diminished LPS-induced NFkappaB and ERK1/2 phosphorylation and the expression of pro-inflammatory genes, indicating that toll-like receptor signaling activation is impaired in the absence of NPC2. Our results suggest that NPC2 is in a mitochondrially associated autophagosome and plays an important role in regulating mitophagy, mitochondrial quality control, and mitochondrial function. PMID- 27402804 TI - QRS duration and ethnicity: implications for heart failure therapy. PMID- 27402801 TI - APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway. AB - The ubiquitin (Ub) ligase anaphase promoting complex/cyclosome (APC/C) and the tumour suppressor retinoblastoma protein (pRB) play key roles in cell cycle regulation. APC/C is a critical regulator of mitosis and G1-phase of the cell cycle whereas pRB keeps a check on proliferation by inhibiting transition to the S-phase. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. Both are also targeted by transforming viruses. We discuss recent advances in our understanding of the involvement of APC/C and pRB in cell cycle based decisions and how these insights will be useful for development of anti cancer and anti-viral drugs. PMID- 27402806 TI - Cochrane corner: does increasing intake of dietary fibre help prevent cardiovascular disease? PMID- 27402805 TI - Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure. AB - BACKGROUND: QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. METHODS: We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. RESULTS: Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for <=120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. CONCLUSION: We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study. PMID- 27402810 TI - Regulation of Hippo signalling by p38 signalling. AB - The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we identify the p38 mitogen-activated protein kinase (MAPK) pathway as a new upstream branch of the Hippo pathway. In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression. Loss-of-function studies show that lic regulates Hippo signalling in ovary follicle cells and in the wing disc. Epistasis analysis indicates that Mekk1 and lic affect Hippo signalling via p38b and wts We further demonstrate that the Mekk1-Lic-p38b cascade inhibits Hippo signalling by promoting F-actin accumulation and Jub phosphorylation. In addition, p38 signalling modulates actin filaments and Hippo signalling in parallel to small GTPases Ras, Rac1, and Rho1. Lastly, we show that p38 signalling regulates Hippo signalling in mammalian cell lines. The Lic homologue MKK3 promotes nuclear localization of YAP via the actin cytoskeleton. Upregulation or downregulation of the p38 pathway regulates YAP-mediated transcription. Our work thus reveals a conserved crosstalk between the p38 MAPK pathway and the Hippo pathway in growth regulation. PMID- 27402812 TI - Mortality trends among Japanese dialysis patients, 1988-2013: a joinpoint regression analysis. AB - BACKGROUND: Evaluation of mortality trends in dialysis patients is important for improving their prognoses. The present study aimed to examine temporal trends in deaths (all-cause, cardiovascular, noncardiovascular and the five leading causes) among Japanese dialysis patients. METHODS: Mortality data were extracted from the Japanese Society of Dialysis Therapy registry. Age-standardized mortality rates were calculated by direct standardization against the 2013 dialysis population. The average annual percentage of change (APC) and the corresponding 95% confidence interval (CI) were computed for trends using joinpoint regression analysis. RESULTS: A total of 469 324 deaths occurred, of which 25.9% were from cardiac failure, 17.5% from infectious disease, 10.2% from cerebrovascular disorders, 8.6% from malignant tumors and 5.6% from cardiac infarction. The joinpoint trend for all-cause mortality decreased significantly, by -3.7% (95% CI -4.2 to -3.2) per year from 1988 through 2000, then decreased more gradually, by 1.4% (95% CI -1.7 to -1.2) per year during 2000-13. The improved mortality rates were mainly due to decreased deaths from cardiovascular disease, with mortality rates due to noncardiovascular disease outnumbering those of cardiovascular disease in the last decade. Among the top five causes of death, cardiac failure has shown a marked decrease in mortality rate. However, the rates due to infectious disease have remained stable during the study period [APC 0.1 (95% CI 0.2-0.3)]. CONCLUSIONS: Significant progress has been made, particularly with regard to the decrease in age-standardized mortality rates. The risk of cardiovascular death has decreased, while the risk of death from infection has remained unchanged for 25 years. PMID- 27402811 TI - Bile acids evoke placental inflammation by activating Gpbar1/NF-kappaB pathway in intrahepatic cholestasis of pregnancy. AB - Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder with potentially deleterious consequences for fetuses. Although a clear correlation between the elevated levels of maternal serum bile acids and deficient fetal outcome has been established in clinical practice, the underlying mechanisms remain elusive. Herein, we report that bile acids induce NF-kappaB pathway activation via G protein-coupled bile acid receptor 1 (Gpbar1), with consequent upregulation of inflammatory genes in trophoblasts, leading to aberrant leukocyte infiltration and inflammation in placenta. Ursodeoxycholic acid (UDCA), a drug used clinically to treat ICP, competes with other bile acids for binding with Gpbar1 and thus inhibits bile acid-induced inflammatory response in trophoblasts and improves fetal survival in pregnant rats with obstructive cholestasis. Notably, inhibition of NF-kappaB by andrographolide is more effective than UDCA in benefiting placentas and fetuses. Thus, anti-inflammation therapy targeting Gpbar1/NF-kappaB pathway could be effective in suppressing bile acid-induced inflammation and alleviating ICP-associated fetal disorders. PMID- 27402813 TI - Erratum for Metrick and Heldwein, Novel Structure and Unexpected RNA-Binding Ability of the C-Terminal Domain of Herpes Simplex Virus 1 Tegument Protein UL21. PMID- 27402816 TI - The Protective Value of Maternal Group B Streptococcus Antibodies: Quantitative and Functional Analysis of Naturally Acquired Responses to Capsular Polysaccharides and Pilus Proteins in European Maternal Sera. AB - BACKGROUND: Group B Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. A vaccine targeting pregnant women could protect infants through placentally transferred antibodies. The association between GBS maternal antibody concentrations and the risk of neonatal infection has been investigated in US and African populations. Here we studied naturally acquired immunoglobulin G (IgG) responses to GBS capsular polysaccharides (CPS) and pilus proteins in European pregnant women. METHODS: Maternal sera were prospectively collected in 8 EU countries from 473 GBS non-colonized and 984 colonized pregnant women who delivered healthy neonates and from 153 mothers of infants with GBS disease. GBS strains from these colonized women and infected infants were obtained in parallel and their capsular and pilus types were identified by serological and molecular methods. Maternal serum concentrations of IgG anti- Ia, -Ib, -III and -V polysaccharides and anti-BP-1, -AP1-2a and -BP-2b pilus proteins were determined by enzyme-linked immunosorbent assay. Antibody functional activity was quantified by Opsonophagocytic Killing Assay. RESULTS: Antibody levels against CPS and pilus proteins were significantly higher in GBS colonized women delivering healthy babies than in mothers of neonates with GBS disease or non-colonized women. Moreover, maternal anti-capsular IgG concentrations showed a significant correlation with functional titers measured by Opsonophagocytic Killing Assay. CONCLUSIONS: Maternal anti-capsular IgG concentrations above 1 ug/mL mediated GBS killing in vitro and were predicted to respectively reduce by 81% (95% confidence interval, 40%-100%) and 78% (45%-100%) the risk of GBS Ia and III early-onset disease in Europe. PMID- 27402817 TI - Switching Lopinavir/Ritonavir to Atazanavir/Ritonavir vs Adding Atorvastatin in HIV-Infected Patients Receiving Second-Line Antiretroviral Therapy With Hypercholesterolemia: A Randomized Controlled Trial. AB - A randomized controlled trial was conducted among human immunodeficiency virus infected patients receiving lopinavir/ritonavir-based regimens with hypercholesterolemia. Reduction of total cholesterol and low-density lipoprotein was significantly greater in patients who were randomized to the addition of atorvastatin compared with those who were switched from lopinavir/ritonavir to atazanavir/ritonavir. PMID- 27402815 TI - Tyrosine receptor kinase B is a drug target in astrocytomas. AB - BACKGROUND: Astrocytomas are the most common primary human brain tumors. Receptor tyrosine kinases (RTKs), including tyrosine receptor kinase B (TrkB, also known as tropomyosin-related kinase B; encoded by neurotrophic tyrosine kinase receptor type 2 [NTRK2]), are frequently mutated by rearrangement/fusion in high-grade and low-grade astrocytomas. We found that activated TrkB can contribute to the development of astrocytoma and might serve as a therapeutic target in this tumor type. METHODS: To identify RTKs capable of inducing astrocytoma formation, a library of human tyrosine kinases was screened for the ability to transform murine Ink4a-/-/Arf-/- astrocytes. Orthotopic allograft studies were conducted to evaluate the effects of RTKs on the development of astrocytoma. Since TrkB was identified as a driver of astrocytoma formation, the effect of the Trk inhibitors AZD1480 and RXDX-101 was assessed in astrocytoma cells expressing activated TrkB. RNA sequencing, real-time PCR, western blotting, and enzyme-linked immunosorbent assays were conducted to characterize NTRK2 in astrocytomas. RESULTS: Activated TrkB cooperated with Ink4a/Arf loss to induce the formation of astrocytomas through a mechanism mediated by activation of signal transducer and activator of transcription 3 (STAT3). TrkB activation positively correlated with Ccl2 expression. TrkB-induced astrocytomas remained dependent on TrkB signaling for survival, highlighting a role of NTRK2 as an addictive oncogene. Furthermore, the QKI-NTRK2 fusion associated with human astrocytoma transformed Ink4a-/-/Arf-/- astrocytes, and this process was also mediated via STAT3 signaling. CONCLUSIONS: Our findings provide evidence that constitutively activated NTRK2 alleles, notably the human tumor-associated QKI-NTRK2 fusion, can cooperate with Ink4a/Arf loss to drive astrocytoma formation. Therefore, we propose NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. PMID- 27402818 TI - Editorial Commentary: Fortune Favors the Bold: Give a Beta-Lactam! PMID- 27402819 TI - Early Response in Cellulitis: A Prospective Study of Dynamics and Predictors. AB - BACKGROUND: Skin and soft tissue infections are common reasons for medical care. Use of broad-spectrum therapy and costs have increased. Assessment of early treatment response has been given a central role both in clinical trials and everyday practice. However, there is a paucity of data on the dynamics of response, causes of early nonresponse, and how early nonresponse affects resource use and predicts outcome. METHODS: We prospectively enrolled 216 patients hospitalized with cellulitis. Clinical and biochemical response data during the first 3 days of treatment were analyzed in relation to baseline factors, antibiotic use, surgery, and outcome. Multivariable analysis included logistic lasso regression. RESULTS: Clinical or biochemical response was observed in the majority of patients the day after treatment initiation. Concordance between clinical and biochemical response was strongest at days 2 and 3. Female sex, cardiovascular disease, higher body mass index, shorter duration of symptoms, and cellulitis other than typical erysipelas were predictors of nonresponse at day 3. In contrast, baseline factors were not predictive of clinical failure assessed posttreatment. Among cases with antibiotic treatment escalation by day 2, 90% (37/41) had nonresponse at day 1, but only 5% (2/40) had inappropriate initial therapy. Nonresponse at day 3 was a predictor of treatment duration >14 days, but not of clinical failure. CONCLUSIONS: Nonpharmacological factors had a major impact on early response dynamics. Delayed response was rarely related to inappropriate therapy but strongly predictive of early treatment escalation, suggesting that broadening antibiotic treatment may often be premature. PMID- 27402820 TI - Impact of Reported Beta-Lactam Allergy on Inpatient Outcomes: A Multicenter Prospective Cohort Study. AB - BACKGROUND: Reported allergy to beta-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate these antibiotics. We prospectively evaluated the impact of these reported allergies on clinical outcomes. METHODS: We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. RESULTS: Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When beta-lactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.28-7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62-2.87). CONCLUSIONS: Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta lactam allergies to safely promote beta-lactam administration among these patients is warranted. PMID- 27402822 TI - Empirical Coverage of Methicillin-Resistant Staphylococcus aureus in Community Acquired Pneumonia: Those Who Do Not Remember the Past Are Doomed to Repeat It. PMID- 27402823 TI - Reply to Chalmers et al. PMID- 27402824 TI - Ouedraogo AL et al (Clin Infect Dis 2015; 60:357-65). PMID- 27402825 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27402826 TI - Flexibility and Solvation of Amyloid-beta Hydrophobic Core. AB - Amyloid fibril deposits found in Alzheimer disease patients are composed of amyloid-beta (Abeta) protein forming a number of hydrophobic interfaces that are believed to be mostly rigid. We have investigated the MUs-ms time-scale dynamics of the intra-strand hydrophobic core and interfaces of the fibrils composed of Abeta1-40 protein. Using solid-state (2)H NMR line shape experiments performed on selectively deuterated methyl groups, we probed the 3-fold symmetric and 2-fold symmetric polymorphs of native Abeta as well as the protofibrils of D23N Iowa mutant, associated with an early onset of Alzheimer disease. The dynamics of the hydrophobic regions probed at Leu-17, Leu-34, Val-36, and Met-35 side chains were found to be very pronounced at all sites and in all polymorphs of Abeta, with methyl axis motions persisting down to 230-200 K for most of the sites. The dominant mode of motions is the rotameric side chain jumps, with the Met-35 displaying the most complex multi-modal behavior. There are distinct differences in the dynamics among the three protein variants, with the Val-36 site displaying the most variability. Solvation of the fibrils does not affect methyl group motions within the hydrophobic core of individual cross-beta subunits but has a clear effect on the motions at the hydrophobic interface between the cross-beta subunits, which is defined by Met-35 contacts. In particular, hydration activates transitions between additional rotameric states that are not sampled in the dry protein. Thus, these results support the existence of water-accessible cavity recently predicted by molecular dynamics simulations and suggested by cryo-EM studies. PMID- 27402827 TI - Wnt-5a/Frizzled9 Receptor Signaling through the Galphao-Gbetagamma Complex Regulates Dendritic Spine Formation. AB - Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Galphao under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Galphao appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gbetagamma is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. PMID- 27402828 TI - Identification of Apolipoprotein A-I as a Retinoic Acid-binding Protein in the Eye. AB - All-trans-retinoic acid may be an important molecular signal in the postnatal control of eye size. The goal of this study was to identify retinoic acid-binding proteins secreted by the choroid and sclera during visually guided ocular growth. Following photoaffinity labeling with all-trans-[11,12-(3)H]retinoic acid, the most abundant labeled protein detected in the conditioned medium of choroid or sclera had an apparent Mr of 27,000 Da. Following purification and mass spectrometry, the Mr 27,000 band was identified as apolipoprotein A-I. Affinity capture of the radioactive Mr 27,000 band by anti-chick apolipoprotein A-I antibodies confirmed its identity as apolipoprotein A-I. Photoaffinity labeling and fluorescence quenching experiments demonstrated that binding of retinoic acid to apolipoprotein A-I is 1) concentration-dependent, 2) selective for all-trans retinoic acid, and 3) requires the presence of apolipoprotein A-I-associated lipids for retinoid binding. Expression of apolipoprotein A-I mRNA and protein synthesis were markedly up-regulated in choroids of chick eyes during the recovery from induced myopia, and apolipoprotein A-I mRNA was significantly increased in choroids following retinoic acid treatment. Together, these data suggest that apolipoprotein A-I may participate in a regulatory feedback mechanism with retinoic acid to control the action of retinoic acid on ocular targets during postnatal ocular growth. PMID- 27402829 TI - The Kinesin-5 Chemomechanical Cycle Is Dominated by a Two-heads-bound State. AB - Single-molecule microscopy and stopped-flow kinetics assays were carried out to understand the microtubule polymerase activity of kinesin-5 (Eg5). Four lines of evidence argue that the motor primarily resides in a two-heads-bound (2HB) state. First, upon microtubule binding, dimeric Eg5 releases both bound ADPs. Second, microtubule dissociation in saturating ADP is 20-fold slower for the dimer than for the monomer. Third, ATP-triggered mant-ADP release is 5-fold faster than the stepping rate. Fourth, ATP binding is relatively fast when the motor is locked in a 2HB state. Shortening the neck-linker does not facilitate rear-head detachment, suggesting a minimal role for rear-head-gating. This 2HB state may enable Eg5 to stabilize incoming tubulin at the growing microtubule plus-end. The finding that slowly hydrolyzable ATP analogs trigger slower nucleotide release than ATP suggests that ATP hydrolysis in the bound head precedes stepping by the tethered head, leading to a mechanochemical cycle in which processivity is determined by the race between unbinding of the bound head and attachment of the tethered head. PMID- 27402830 TI - Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells. AB - O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked beta-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma. PMID- 27402831 TI - cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases. AB - cis-Prenyltransferases (cis-PTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. cis-PTs catalyze consecutive condensation reactions of allylic diphosphate acceptor with isopentenyl diphosphate (IPP) in the cis (Z) configuration to generate linear polyprenyl diphosphate. The chain lengths of isoprenoid carbon skeletons vary widely from neryl pyrophosphate (C10) to natural rubber (C>10,000). The homo-dimeric bacterial enzyme, undecaprenyl diphosphate synthase (UPPS), has been structurally and mechanistically characterized in great detail and serves as a model for understanding the mode of action of eukaryotic cis-PTs. However, recent experiments have revealed that mammals, fungal, and long-chain plant cis-PTs are heteromeric enzymes composed of two distantly related subunits. In this review, the classification, function, and evolution of cis-PTs will be discussed with a special emphasis on the role of the newly described NgBR/Nus1 subunit and its plants' orthologs as essential, structural components of the cis-PTs activity. PMID- 27402832 TI - Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria. AB - Two protein translocases transport precursor proteins into or across the inner mitochondrial membrane. The presequence translocase (TIM23 complex) sorts precursor proteins with a cleavable presequence either into the matrix or into the inner membrane. The carrier translocase (TIM22 complex) inserts multispanning proteins into the inner membrane. Both protein import pathways depend on the presence of a membrane potential, which is generated by the activity of the respiratory chain. The non-bilayer-forming phospholipids cardiolipin and phosphatidylethanolamine are required for the activity of the respiratory chain and therefore to maintain the membrane potential for protein import. Depletion of cardiolipin further affects the stability of the TIM23 complex. The role of bilayer-forming phospholipids like phosphatidylcholine (PC) in protein transport into the inner membrane and the matrix is unknown. Here, we report that import of presequence-containing precursors and carrier proteins is impaired in PC deficient mitochondria. Surprisingly, depletion of PC does not affect stability and activity of respiratory supercomplexes, and the membrane potential is maintained. Instead, the dynamic TIM23 complex is destabilized when the PC levels are reduced, whereas the TIM22 complex remains intact. Our analysis further revealed that initial precursor binding to the TIM23 complex is impaired in PC deficient mitochondria. We conclude that reduced PC levels differentially affect the TIM22 and TIM23 complexes in mitochondrial protein transport. PMID- 27402833 TI - Structure and Glycan Binding of a New Cyanovirin-N Homolog. AB - The HIV-1 envelope glycoprotein gp120 is heavily glycosylated and bears numerous high mannose sugars. These sugars can serve as targets for HIV-inactivating compounds, such as antibodies and lectins, which bind to the glycans and interfere with viral entry into the target cell. We determined the 1.6 A x-ray structure of Cyt-CVNH, a recently identified lectin from the cyanobacterium Cyanothece(7424), and elucidated its glycan specificity by NMR. The Cyt-CVNH structure and glycan recognition profile are similar to those of other CVNH proteins, with each domain specifically binding to Manalpha(1-2)Manalpha units on the D1 and D3 arms of high mannose glycans. However, in contrast to CV-N, no cross-linking and precipitation of the cross-linked species in solution was observed upon Man-9 binding, allowing, for the first time, investigation of the interaction of Man-9 with a member of the CVNH family by NMR. HIV assays showed that Cyt-CVNH is able to inhibit HIV-1 with ~4-fold higher potency than CV N(P51G), a stabilized version of wild type CV-N. Therefore, Cyt-CVNH may qualify as a valuable lectin for potential microbicidal use. PMID- 27402834 TI - Targeted Reconstitution of Cytokine Activity upon Antigen Binding using Split Cytokine Antibody Fusion Proteins. AB - The targeted assembly of antibody products upon antigen binding represents a novel strategy for the reconstitution of potent therapeutic activity at the site of disease, sparing healthy tissues. We demonstrate that interleukin-12, a heterodimeric pro-inflammatory cytokine consisting of the disulfide-linked p40 and p35 subunits, can be reconstituted by sequential reassembly of fusion proteins based on antibody fragments and interleukin-12 subunit mutants. Analysis of the immunostimulatory properties of interleukin-12 and its derivatives surprisingly revealed that the mutated p35 subunit partially retained the activity of the parental cytokine, whereas the p40 subunit alone was not able to stimulate T cells or natural killer cells. The concept of stepwise antibody-based reassembly of split cytokines could be useful for the development of other anticancer therapeutics with improved safety and tolerability. PMID- 27402835 TI - Enzymatically Inactive Procaspase 1 stabilizes the ASC Pyroptosome and Supports Pyroptosome Spreading during Cell Division. AB - Caspase-1 is a key player during the initiation of pro-inflammatory innate immune responses, activating pro-IL-1beta in so-called inflammasomes. A subset of patients with recurrent febrile episodes and systemic inflammation of unknown origin harbor mutations in CASP1 encoding caspase-1. CASP1 variants result in reduced enzymatic activity of caspase-1 and impaired IL-1beta secretion. The apparent paradox of reduced IL-1beta secretion but systemic inflammation led to the hypothesis that CASP1 mutations may result in variable protein interaction clusters, thus activating alternative signaling pathways. To test this hypothesis, we established and characterized an in vitro system of transduced immortalized murine macrophages expressing either WT or enzymatically inactive (p.C284A) procaspase-1 fusion reporter proteins. Macrophages with variant p.C284A caspase-1 did not secrete IL-1beta and exhibited reduced inflammatory cell death, referred to as pyroptosis. Caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) formed cytosolic macromolecular complexes (so-called pyroptosomes) that were significantly increased in number and size in cells carrying the p.C284A caspase-1 variant compared with WT caspase-1. Furthermore, enzymatically inactive caspase-1 interacted with ASC longer and with increased intensity compared with WT caspase-1. Applying live cell imaging, we documented for the first time that pyroptosomes containing enzymatically inactive variant p.C284A caspase-1 spread during cell division. In conclusion, variant p.C284A caspase-1 stabilizes pyroptosome formation, potentially enhancing inflammation by two IL-1beta-independent mechanisms: pyroptosomes convey an enhanced inflammatory stimulus through the recruitment of additional proteins (such as RIP2, receptor interacting protein kinase 2), which is further amplified through pyroptosome and cell division. PMID- 27402836 TI - Collagen Accumulation in Osteosarcoma Cells lacking GLT25D1 Collagen Galactosyltransferase. AB - Collagen is post-translationally modified by prolyl and lysyl hydroxylation and subsequently by glycosylation of hydroxylysine. Despite the widespread occurrence of the glycan structure Glc(alpha1-2)Gal linked to hydroxylysine in animals, the functional significance of collagen glycosylation remains elusive. To address the role of glycosylation in collagen expression, folding, and secretion, we used the CRISPR/Cas9 system to inactivate the collagen galactosyltransferase GLT25D1 and GLT25D2 genes in osteosarcoma cells. Loss of GLT25D1 led to increased expression and intracellular accumulation of collagen type I, whereas loss of GLT25D2 had no effect on collagen secretion. Inactivation of the GLT25D1 gene resulted in a compensatory induction of GLT25D2 expression. Loss of GLT25D1 decreased collagen glycosylation by up to 60% but did not alter collagen folding and thermal stability. Whereas cells harboring individually inactivated GLT25D1 and GLT25D2 genes could be recovered and maintained in culture, cell clones with simultaneously inactive GLT25D1 and GLT25D2 genes could be not grown and studied, suggesting that a complete loss of collagen glycosylation impairs osteosarcoma cell proliferation and viability. PMID- 27402837 TI - Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity. AB - Macrophages play crucial roles in combatting infectious disease by promoting inflammation and phagocytosis. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor that induces tissue inflammation by attracting and activating macrophages to produce inflammatory cytokines in chronic inflammation-associated diseases such as obesity-associated metabolic syndrome, atherosclerosis, and rheumatoid arthritis. Here, we asked whether and how ANGPTL2 activates macrophages in the innate immune response. ANGPTL2 was predominantly expressed in proinflammatory mouse bone marrow-derived differentiated macrophages (GM-BMMs) following GM-CSF treatment relative to anti-inflammatory cells (M-BMMs) established by M-CSF treatment. Expression of the proinflammatory markers IL 1beta, IL-12p35, and IL-12p40 significantly decreased in GM-BMMs from Angptl2 deficient compared with wild-type (WT) mice, suggestive of attenuated proinflammatory activity. We also report that ANGPTL2 inflammatory signaling is transduced through integrin alpha5beta1 rather than through paired immunoglobulin like receptor B. Interestingly, Angptl2-deficient mice were more susceptible to infection with Salmonella enterica serovar Typhimurium than were WT mice. Moreover, nitric oxide (NO) production by Angptl2-deficient GM-BMMs was significantly lower than in WT GM-BMMs. Collectively, our findings suggest that macrophage-derived ANGPTL2 promotes an innate immune response in those cells by enhancing proinflammatory activity and NO production required to fight infection. PMID- 27402838 TI - Integrator of Stress Responses Calmodulin Binding Transcription Activator 1 (Camta1) Regulates miR-212/miR-132 Expression and Insulin Secretion. AB - Altered microRNA profiles have been demonstrated in experimental models of type 2 diabetes, including in islets of the diabetic Goto-Kakizaki (GK) rat. Our bioinformatic analysis of conserved sequences in promoters of microRNAs, previously observed to be up-regulated in GK rat islets, revealed putative CGCG core motifs on the promoter of the miR-212/miR-132 cluster, overexpression of which has been shown to increase insulin secretion. These motifs are possible targets of calmodulin binding transcription activators Camta1 and Camta2 that have been recognized as integrators of stress responses. We also identified putative NKE elements, possible targets of NK2 homeobox proteins like the essential islet transcription factor Nkx2-2. As Camtas can function as co activators with NK2 proteins in other tissues, we explored the role of Camta1, Camta2, and Nkx2-2 in the regulation of the miR-212/miR-132 cluster and insulin secretion. We demonstrate that exposure of control Wistar or GK rat islets to 16.7 mm glucose increases miR-212/miR-132 expression but significantly less so in the GK rat. In addition, Camta1, Camta2, and Nkx2-2 were down-regulated in GK rat islets, and knockdown of Camta1 reduced miR-212/miR-132 promoter activity and miR 212/miR-132 expression, even under cAMP elevation. Knockdown of Camta1 decreased insulin secretion in INS-1 832/13 cells and Wistar rat islets but increased insulin content. Furthermore, knockdown of Camta1 reduced K(+)-induced insulin secretion and voltage-dependent Ca(2+) currents. We also demonstrate Camta1 and Nkx2-2 protein interaction. These results indicate that Camta1 is required not only for expression of the miR-212/miR-132 cluster but at multiple levels for regulating beta cell insulin content and secretion. PMID- 27402839 TI - High Affinity Binding of the Receptor-associated Protein D1D2 Domains with the Low Density Lipoprotein Receptor-related Protein (LRP1) Involves Bivalent Complex Formation: CRITICAL ROLES OF LYSINES 60 AND 191. AB - The LDL receptor-related protein 1 (LRP1) is a large endocytic receptor that binds and mediates the endocytosis of numerous structurally diverse ligands. Currently, the basis for ligand recognition by LRP1 is not well understood. LRP1 requires a molecular chaperone, termed the receptor-associated protein (RAP), to escort the newly synthesized receptor from the endoplasmic reticulum to the Golgi. RAP is a three-domain protein that contains the following two high affinity binding sites for LRP1: one is located within domains 1 and 2, and one is located in its third domain. Studies on the interaction of the RAP third domain with LRP1 reveal critical contributions by lysine 256 and lysine 270 for this interaction. From these studies, a model for ligand recognition by this class of receptors has been proposed. Here, we employed surface plasmon resonance to investigate the binding of RAP D1D2 to LRP1. Our results reveal that the high affinity of D1D2 for LRP1 results from avidity effects mediated by the simultaneous interactions of lysine 60 in D1 and lysine 191 in D2 with sites on LRP1 to form a bivalent D1D2-LRP1 complex. When lysine 60 and 191 are both mutated to alanine, the binding of D1D2 to LRP1 is ablated. Our data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors, which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor. PMID- 27402840 TI - Accessory Interaction Motifs in the Atg19 Cargo Receptor Enable Strong Binding to the Clustered Ubiquitin-related Atg8 Protein. AB - Selective autophagy contributes to cellular homeostasis by delivering harmful material into the lysosomal system for degradation via vesicular intermediates referred to as autophagosomes. The cytoplasm-to-vacuole targeting pathway is a variant of selective autophagy in Saccharomyces cerevisiae during which hydrolases such as prApe1 are transported into the vacuole. In general, selectivity is achieved by autophagic cargo receptors that link the cargo to autophagosomal membranes because of their ability to simultaneously interact with the cargo and Atg8 proteins that coat the membrane. The Atg19 receptor contains multiple Atg8 interaction sites in its C terminus in addition to a canonical Atg8 interacting LC3-interacting region (LIR, with LC3 being a homolog of Atg8) motif, but their mode of interaction with Atg8 is unclear. Here we show, using a combination of NMR, microscopy-based interaction assays, and prApe1 processing experiments, that two additional sites interact with Atg8 in a LIR-like and thus mutually exclusive manner. We term these motifs accessory LIR motifs because their affinities are lower than that of the canonical LIR motif. Thus, one Atg19 molecule has the ability to interact with multiple Atg8 proteins simultaneously, resulting in a high-avidity interaction that may confer specific binding to the Atg8-coated autophagosomal membrane on which Atg8 is concentrated. PMID- 27402841 TI - Novel Roles and Mechanism for Kruppel-like Factor 16 (KLF16) Regulation of Neurite Outgrowth and Ephrin Receptor A5 (EphA5) Expression in Retinal Ganglion Cells. AB - Regenerative medicine holds great promise for the treatment of degenerative retinal disorders. Kruppel-like factors (KLFs) are transcription factors that have recently emerged as key tools in regenerative medicine because some of them can function as epigenetic reprogrammers in stem cell biology. Here, we show that KLF16, one of the least understood members of this family, is a POU4F2 independent transcription factor in retinal ganglion cells (RGCs) as early as embryonic day 15. When overexpressed, KLF16 inhibits RGC neurite outgrowth and enhances RGC growth cone collapse in response to exogenous ephrinA5 ligands. Ephrin/EPH signaling regulates RGC connectivity. The EphA5 promoter contains multiple GC- and GT-rich KLF-binding sites, which, as shown by ChIP-assays, bind KLF16 in vivo In electrophoretic mobility shift assays, KLF16 binds specifically to a single KLF site near the EphA5 transcription start site that is required for KLF16 transactivation. Interestingly, methylation of only six of 98 CpG dinucleotides within the EphA5 promoter blocks its transactivation by KLF16 but enables transactivation by KLF2 and KLF15. These data demonstrate a role for KLF16 in regulation of RGC neurite outgrowth and as a methylation-sensitive transcriptional regulator of EphA5 expression. Together, these data identify differential low level methylation as a novel mechanism for regulating KLF16 mediated EphA5 expression across the retina. Because of the critical role of ephrin/EPH signaling in patterning RGC connectivity, understanding the role of KLFs in regulating neurite outgrowth and Eph receptor expression will be vital for successful restoration of functional vision through optic nerve regenerative therapies. PMID- 27402842 TI - Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow derived Mesenchymal Stem Cells. AB - Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARgamma are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSCs). As assessed by ChIP sequencing and RNA-sequencing analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPbeta, retinoid X receptor, and vitamin D receptor binding sites, whereas adipocyte differentiation favored PPARgamma, retinoid X receptor, C/EBPalpha, and C/EBPbeta binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg, and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment, as assessed by staining, gene expression, and ChIP quantitative PCR analysis. The osteogenic default pathway may be subverted during pathological conditions, leading to skeletal fragility and increased marrow adiposity during aging, estrogen deficiency, and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies. PMID- 27402843 TI - beta-Apo-10'-carotenoids Modulate Placental Microsomal Triglyceride Transfer Protein Expression and Function to Optimize Transport of Intact beta-Carotene to the Embryo. AB - beta-Carotene is an important source of vitamin A for the mammalian embryo, which depends on its adequate supply to achieve proper organogenesis. In mammalian tissues, beta-carotene 15,15'-oxygenase (BCO1) converts beta-carotene to retinaldehyde, which is then oxidized to retinoic acid, the biologically active form of vitamin A that acts as a transcription factor ligand to regulate gene expression. beta-Carotene can also be cleaved by beta-carotene 9',10'-oxygenase (BCO2) to form beta-apo-10'-carotenal, a precursor of retinoic acid and a transcriptional regulator per se The mammalian embryo obtains beta-carotene from the maternal circulation. However, the molecular mechanisms that enable its transfer across the maternal-fetal barrier are not understood. Given that beta carotene is transported in the adult bloodstream by lipoproteins and that the placenta acquires, assembles, and secretes lipoproteins, we hypothesized that the aforementioned process requires placental lipoprotein biosynthesis. Here we show that beta-carotene availability regulates transcription and activity of placental microsomal triglyceride transfer protein as well as expression of placental apolipoprotein B, two key players in lipoprotein biosynthesis. We also show that beta-apo-10'-carotenal mediates the transcriptional regulation of microsomal triglyceride transfer protein via hepatic nuclear factor 4alpha and chicken ovalbumin upstream promoter transcription factor I/II. Our data provide the first in vivo evidence of the transcriptional regulatory activity of beta apocarotenoids and identify microsomal triglyceride transfer protein and its transcription factors as the targets of their action. This study demonstrates that beta-carotene induces a feed-forward mechanism in the placenta to enhance the assimilation of beta-carotene for proper embryogenesis. PMID- 27402844 TI - Protease-activated Receptor-4 Signaling and Trafficking Is Regulated by the Clathrin Adaptor Protein Complex-2 Independent of beta-Arrestins. AB - Protease-activated receptor-4 (PAR4) is a G protein-coupled receptor (GPCR) for thrombin and is proteolytically activated, similar to the prototypical PAR1. Due to the irreversible activation of PAR1, receptor trafficking is intimately linked to signal regulation. However, unlike PAR1, the mechanisms that control PAR4 trafficking are not known. Here, we sought to define the mechanisms that control PAR4 trafficking and signaling. In HeLa cells depleted of clathrin by siRNA, activated PAR4 failed to internalize. Consistent with clathrin-mediated endocytosis, expression of a dynamin dominant-negative K44A mutant also blocked activated PAR4 internalization. However, unlike most GPCRs, PAR4 internalization occurred independently of beta-arrestins and the receptor's C-tail domain. Rather, we discovered a highly conserved tyrosine-based motif in the third intracellular loop of PAR4 and found that the clathrin adaptor protein complex-2 (AP-2) is important for internalization. Depletion of AP-2 inhibited PAR4 internalization induced by agonist. In addition, mutation of the critical residues of the tyrosine-based motif disrupted agonist-induced PAR4 internalization. Using Dami megakaryocytic cells, we confirmed that AP-2 is required for agonist-induced internalization of endogenous PAR4. Moreover, inhibition of activated PAR4 internalization enhanced ERK1/2 signaling, whereas Akt signaling was markedly diminished. These findings indicate that activated PAR4 internalization requires AP-2 and a tyrosine-based motif and occurs independent of beta-arrestins, unlike most classical GPCRs. Moreover, these findings are the first to show that internalization of activated PAR4 is linked to proper ERK1/2 and Akt activation. PMID- 27402845 TI - Reversal of Ethanol-induced Intoxication by a Novel Modulator of Gbetagamma Protein Potentiation of the Glycine Receptor. AB - The acute intoxicating effects of ethanol in the central nervous system result from the modulation of several molecular targets. It is widely accepted that ethanol enhances the activity of the glycine receptor (GlyR), thus enhancing inhibitory neurotransmission, leading to motor effects, sedation, and respiratory depression. We previously reported that small peptides interfered with the binding of Gbetagamma to the GlyR and consequently inhibited the ethanol-induced potentiation of the receptor. Now, using virtual screening, we identified a subset of small molecules capable of interacting with the binding site of Gbetagamma. One of these compounds, M554, inhibited the ethanol potentiation of the GlyR in both evoked currents and synaptic transmission in vitro When this compound was tested in vivo in mice treated with ethanol (1-3.5 g/kg), it was found to induce a faster recovery of motor incoordination in rotarod experiments and a shorter sedative effect in loss of righting reflex assays. This study describes a novel molecule that might be relevant for the design of useful therapeutic compounds in the treatment of acute alcohol intoxication. PMID- 27402846 TI - Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity: EFFECTS ON EMBRYO SURVIVAL. AB - Fibulin-1 (FBLN1) is a member of a growing family of extracellular matrix glycoproteins that includes eight members and is involved in cellular functions such as adhesion, migration, and differentiation. FBLN1 has also been implicated in embryonic heart and valve development and in the formation of neural crest derived structures, including aortic arch, thymus, and cranial nerves. Fibroblast growth factor 8 (FGF8) is a member of a large family of growth factors, and its functions include neural crest cell (NCC) maintenance, specifically NCC migration as well as patterning of structures formed from NCC such as outflow tract and cranial nerves. In this report, we sought to investigate whether FBLN1 and FGF8 have cooperative roles in vivo given their influence on the development of the same NCC-derived structures. Surface plasmon resonance binding data showed that FBLN1 binds tightly to FGF8 and prevents its enzymatic degradation by ADAM17. Moreover, overexpression of FBLN1 up-regulates FGF8 gene expression, and down regulation of FBLN1 by siRNA inhibits FGF8 expression. The generation of a double mutant Fbln1 and Fgf8 mice (Fbln1(-/-) and Fgf8(-/-)) showed that haplo insufficiency (Fbln1(+/-) and Fgf8(+/-)) resulted in increased embryonic mortality compared with single heterozygote crosses. The mortality of the FGF8/Fbln1 double heterozygote embryos occurred between 14.5 and 16.5 days post coitus. In conclusion, FBLN1/FGF8 interaction plays a role in survival of vertebrate embryos, and reduced levels of both proteins resulted in added mortality in utero The FBLN1/FGF8 interaction may also be involved in the survival of neural crest cell population during development. PMID- 27402847 TI - Heat Shock Protein 90 kDa (Hsp90) Has a Second Functional Interaction Site with the Mitochondrial Import Receptor Tom70. AB - To accomplish its crucial role, mitochondria require proteins that are produced in the cytosol, delivered by cytosolic Hsp90, and translocated to its interior by the translocase outer membrane (TOM) complex. Hsp90 is a dimeric molecular chaperone and its function is modulated by its interaction with a large variety of co-chaperones expressed within the cell. An important family of co-chaperones is characterized by the presence of one TPR (tetratricopeptide repeat) domain, which binds to the C-terminal MEEVD motif of Hsp90. These include Tom70, an important component of the TOM complex. Despite a wealth of studies conducted on the relevance of Tom70.Hsp90 complex formation, there is a dearth of information regarding the exact molecular mode of interaction. To help fill this void, we have employed a combined experimental strategy consisting of cross-linking/mass spectrometry to investigate binding of the C-terminal Hsp90 domain to the cytosolic domain of Tom70. This approach has identified a novel region of contact between C-Hsp90 and Tom70, a finding that is confirmed by probing the corresponding peptides derived from cross-linking experiments via isothermal titration calorimetry and mitochondrial import assays. The data generated in this study are combined to input constraints for a molecular model of the Hsp90/Tom70 interaction, which has been validated by small angle x-ray scattering, hydrogen/deuterium exchange, and mass spectrometry. The resultant model suggests that only one of the MEEVD motifs within dimeric Hsp90 contacts Tom70. Collectively, our findings provide significant insight on the mechanisms by which preproteins interact with Hsp90 and are translocated via Tom70 to the mitochondria. PMID- 27402848 TI - Misregulation of a DDHD Domain-containing Lipase Causes Mitochondrial Dysfunction in Yeast. AB - The DDHD domain-containing proteins, which belong to the intracellular phospholipase A1 (iPLA1) family, have been predicted to be involved in phospholipid metabolism, lipid trafficking, membrane turnover, and signaling. Defective cardiolipin (CL), phosphatidylethanolamine, and phosphatidylglycerol remodeling cause Barth syndrome and mitochondrial dysfunction. Here, we report that Yor022c is a Ddl1 (DDHD domain-containing lipase 1) that hydrolyzes CL, phosphatidylethanolamine, and phosphatidylglycerol. Ddl1 has been implicated in the remodeling of mitochondrial phospholipids and CL degradation. Our data also suggested that the accumulation of monolysocardiolipin is deleterious to the cells. We show that Aft1 and Aft2 transcription factors antagonistically regulate the DDL1 gene. This study reveals that the misregulation of DDL1 by Aft1/2 transcription factors alters CL metabolism and causes mitochondrial dysfunction in the cells. In humans, mutations in the DDHD1 and DDHD2 genes cause specific types of hereditary spastic paraplegia (SPG28 and SPG54, respectively), and the yeast DDL1-defective strain produces similar phenotypes of hereditary spastic paraplegia (mitochondrial dysfunction and defects in lipid metabolism). Therefore, the DDL1-defective strain could be a good model system for understanding hereditary spastic paraplegia. PMID- 27402849 TI - Discovery of a Unique Extracellular Polysaccharide in Members of the Pathogenic Bacillus That Can Co-form with Spores. AB - An exopolysaccharide, produced during the late stage of stationary growth phase, was discovered and purified from the culture medium of Bacillus cereus, Bacillus anthracis, and Bacillus thuringiensis when strains were grown in a defined nutrient medium that induces biofilm. Two-dimensional NMR structural characterization of the polysaccharide, named pzX, revealed that it is composed of an unusual three amino-sugar sequence repeat of [-3)XylNAc4OAc(alpha1 3)GlcNAcA4OAc(alpha1-3)XylNAc(alpha1-]n The sugar residue XylNAc had never been described previously in any glycan structure. The XNAC operon that contains the genes for the assembly of pzX is also unique and so far has been identified only in members of the Bacillus cereus sensu lato group. Microscopic and biochemical analyses indicate that pzX co-forms during sporulation, so that upon the release of the spore to the extracellular milieu it becomes surrounded by pzX. The relative amounts of pzX produced can be manipulated by specific nutrients in the medium, but rich medium appears to suppress pzX formation. pzX has the following unique characteristics: a surfactant property that lowers surface tension, a cell/spore antiaggregant, and an adherence property that increases spores binding to surfaces. pzX in Bacillus could represent a trait shared by many spore producing microorganisms. It suggests pzX is an active player in spore physiology and may provide new insights to the successful survival of the B. cereus species in natural environments or in the hosts. PMID- 27402850 TI - Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke. AB - An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. PMID- 27402851 TI - Electrochemical Evidence for Neuroglobin Activity on NO at Physiological Concentrations. AB - The true function of neuroglobin (Ngb) and, particularly, human Ngb (NGB) has been under debate since its discovery 15 years ago. It has been expected to play a role in oxygen binding/supply, but a variety of other functions have been put forward, including NO dioxygenase activity. However, in vitro studies that could unravel these potential roles have been hampered by the lack of an Ngb-specific reductase. In this work, we used electrochemical measurements to investigate the role of an intermittent internal disulfide bridge in determining NO oxidation kinetics at physiological NO concentrations. The use of a polarized electrode to efficiently interconvert the ferric (Fe(3+)) and ferrous (Fe(2+)) forms of an immobilized NGB showed that the disulfide bridge both defines the kinetics of NO dioxygenase activity and regulates appearance of the free ferrous deoxy-NGB, which is the redox active form of the protein in contrast to oxy-NGB. Our studies further identified a role for the distal histidine, interacting with the hexacoordinated iron atom of the heme, in oxidation kinetics. These findings may be relevant in vivo, for example, in blocking apoptosis by reduction of ferric cytochrome c, and gentle tuning of NO concentration in the tissues. PMID- 27402852 TI - Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE. AB - Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 A) and in complex with its allosteric activator AMP (3.4 A). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID- 27402853 TI - Biophysical and Structural Characterization of the Centriolar Protein Cep104 Interaction Network. AB - Dysfunction of cilia is associated with common genetic disorders termed ciliopathies. Knowledge on the interaction networks of ciliary proteins is therefore key for understanding the processes that are underlying these severe diseases and the mechanisms of ciliogenesis in general. Cep104 has recently been identified as a key player in the regulation of cilia formation. Using a combination of sequence analysis, biophysics, and x-ray crystallography, we obtained new insights into the domain architecture and interaction network of the Cep104 protein. We solved the crystal structure of the tumor overexpressed gene (TOG) domain, identified Cep104 as a novel tubulin-binding protein, and biophysically characterized the interaction of Cep104 with CP110, Cep97, end binding (EB) protein, and tubulin. Our results represent a solid platform for the further investigation of the microtubule-EB-Cep104-tubulin-CP110-Cep97 network of proteins. Ultimately, such studies should be of importance for understanding the process of cilia formation and the mechanisms underlying different ciliopathies. PMID- 27402854 TI - Prevalence, Features, and Prognostic Importance of Edge Dissection After Drug Eluting Stent Implantation: An ADAPT-DES Intravascular Ultrasound Substudy. AB - BACKGROUND: Intravascular ultrasound detects stent edge dissections after percutaneous coronary intervention that are not seen angiographically. This study investigated the association between stent edge dissections and clinical outcomes. METHODS AND RESULTS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a large-scale, prospective, multicenter study of patients undergoing drug-eluting stent implantation. In this prospective substudy, 2062 patients (2433 lesions) were evaluated with intravascular ultrasound to characterize the morphological features and clinical outcomes of stent edge dissection after percutaneous coronary intervention. The prevalence of post-percutaneous coronary intervention stent edge dissection was 6.6% per lesion (161 of 2433). Calcified plaque at the proximal stent edge (relative risk [RR]=1.72; P=0.04) and proximal stent edge expansion (RR=1.18; P=0.004) were predictors for proximal dissection; attenuated plaque at the distal stent edge (RR=3.52; P=0.004), distal reference plaque burden (RR=1.56; P<0.0001), and distal edge stent expansion (RR=1.11; P=0.02) were predictors for distal dissection. At 1-year follow-up, target lesion revascularization was more common in lesions with versus without dissection (5.2% versus 2.7%; P=0.04). Multivariable analysis indicated that residual dissection was associated with target lesion revascularization at 1-year follow-up (RR=2.67; P=0.02). Among lesions with dissection, smaller effective lumen area increased the risk of target lesion revascularization at 1-year follow-up (cutoff value of 5.1 mm(2); P=0.05). CONCLUSIONS: Greater stent expansion and the presence of large, calcified, and/or attenuated plaques were independent predictors of stent edge dissection. Residual stent edge dissection, especially with a smaller effective lumen area, was associated with target lesion revascularization during 1-year follow-up after drug-eluting stent implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794. PMID- 27402855 TI - Duration of benefit following completion of pulmonary rehabilitation in interstitial lung disease-an observational study. AB - BACKGROUND: It remains unclear for how long the benefits of pulmonary rehabilitation (PR) last in interstitial lung disease (ILD). An increasing number of ILD patients complete PR and it is vital they be offered the most beneficial approaches. METHODS: This is a retrospective, observational study of a cohort with ILD who had completed PR. Incremental shuttle walk (ISWT) and chronic respiratory disease questionnaire (CRDQ) were compared before PR, at course completion, and 6/12 months follow-up. Focus group discussions with ILD participants who had completed PR and their carers established qualitative views on existing and potential future PR provision. RESULTS: 79 participants with ILD were identified at course completion, with 39 followed to 12 months. 11 participants died during follow-up. Initial benefits from PR were not sustained at 6 months (ISWT change 0.0m (95% CI-23.2 to 23.2 m), CRDQ change 2.5 (95% CI 2.4 to 7.4)) and 12 months (ISWT change-0.7 m (95% CI-37.3 to 35.9 m), CRDQ change 4.0 (95% CI-2.2 to 10.2)). Continued home exercise gave longer lasting benefit in exercise capacity. Focus group discussions highlighted the value attached to PR and suggested areas for improvement. CONCLUSIONS: Standard PR gives initial benefits in participants with ILD who complete the course, however these are not sustained. Tailored approaches to this group would be appreciated by this group and should be explored. PMID- 27402856 TI - Left atrial myxoma. PMID- 27402857 TI - Endovascular treatment of acute ischemic stroke in nonagenarians compared with younger patients in a multicenter cohort. AB - BACKGROUND: Recent studies have demonstrated the superiority of endovascular therapy (EVT) for emergent large vessel occlusion. OBJECTIVE: To determine the effectiveness of EVT in nonagenarians, for whom data are limited. METHODS: We retrospectively reviewed clinical and imaging data of all patients who underwent EVT at two stroke centers between January 2012 and August 2014. The 90-day functional outcome (modified Rankin Scale (mRS) score) was compared between younger patients (age 18-89 years; n=175) and nonagenarians (n=18). The relationship between pre-stroke and 90-day post-stroke mRS was analyzed in these two groups. Multivariable analysis of age, recanalization grade, and admission National Institutes of Health Stroke Scale (NIHSS) for predicting outcome was performed. RESULTS: Age >=90 years was associated with a poor (mRS >2) 90-day outcome relative to those under 90 (89% vs 52%, OR=8, 95% CI 1.7 to 35.0; p=0.0081). Nonagenarians had a higher pre-stroke mRS score (0.77; 95% CI 0.44 to 1.30) than younger patients (0.24; 95% CI 0.17 to 0.35; p=0.005). No difference was observed between nonagenarians and younger patients in the rate of mRS change from pre-stroke to 90 days (p=0.540). On multivariable regression, age (OR=1.05, 95% CI 1.03 to 1.08; p<0.0001), recanalization grade (OR=0.62 95% CI 0.42 to 0.91; p=0.015), and admission NIHSS (OR=1.07 95% CI 1.02 to 1.13; p=0.01) were associated with a poor 90-day outcome. CONCLUSIONS: Nonagenarians are at a substantially higher risk of a poor 90-day outcome after EVT than younger patients. However, a small subset of nonagenarians may benefit from EVT, particularly if they have a good pre-stroke functional status. Further research is needed to identify factors associated with favorable outcome in this age cohort. PMID- 27402858 TI - Long term durability and outcomes of carotid stenting and carotid endarterectomy. AB - PURPOSE: To evaluate the long term durability and outcomes of carotid angioplasty and stenting (CAS) compared with carotid endarterectomy (CEA). METHODS: Using multiple comprehensive databases, we searched for randomized controlled trials comparing CAS with CEA for carotid stenosis. Studies were classified according to symptom status: symptomatic, asymptomatic, or all inclusive stenosis. Postprocedural ipsilateral stroke, restenosis/occlusion after revascularization, procedural stroke/death/myocardial infarction (MI), and postprocedural ipsilateral stroke were evaluated. Subgroup analysis was performed according to follow-up duration. RESULTS: 22 studies were included and classified for meta analyses in relation to specific outcomes. The maximum follow-up duration was 10 years. The risk of postprocedural ipsilateral stroke in CEA was equivalent to that in CAS, irrespective of symptom status or follow-up time points. The CAS group had a greater risk of restenosis/occlusion after revascularization compared with CEA in studies of all inclusive stenosis. A similar tendency was found in studies of symptomatic stenosis, but without statistical significance. However, subgroup analysis showed that the risk of restenosis/occlusion in CAS decreased gradually with time, to the extent that these risks became comparable 1 year after the procedure. Procedural stroke/death/MI and postprocedural ipsilateral stroke occurred more frequently in the CAS group in studies of symptomatic stenosis although not in studies of asymptomatic or all inclusive stenosis. However, this association did not persist when studies were divided according to follow-up time points. CONCLUSIONS: Although CAS may be more strongly associated with periprocedural stroke/death compared with CEA, it could be a good alternative to CEA in terms of long term durability and outcomes. PMID- 27402859 TI - Decreasing procedure times with a standardized approach to ELVO cases. AB - BACKGROUND: Embolectomy is the standard of care for emergent large vessel occlusion (ELVO), and needs to be done as quickly as possible for the best possible outcomes. Optimization of workflow and process is certainly paramount. One aspect of this is process improvement to standardize as much as possible the procedure in order to decrease variability among operators, which breeds familiarity for the entire team. OBJECTIVE: To evaluate the impact of a standardized approach to ELVO cases in decreasing times from groin puncture to first deployment of a stent-retriever and final recanalization. METHODS: A retrospective review of 83 consecutive patients consisting of a pre standardization phase (group 1) and those after standardization (group 2). The standardization process involved all three neurointerventional radiologists agreeing on a standard approach to the cases and to the equipment to be used. Times from groin puncture to first deployment of the stent-retriever and from puncture to final reperfusion were evaluated. Angiographic outcomes were scored using the Modified Thrombolysis in Cerebral Ischemia (mTICI) score. Complications from intracranial catheter manipulation (such as wire perforation) were also recorded. Clinical outcomes were assessed based on admission and discharge National Institute of Health Stroke Scale score. RESULTS: There were 22 patients in group 1 and 61 patients in group 2. Mean times from groin puncture to first deployment were 39.8 min in group 1 and 20 min in group 2, a difference which was statistically significant (p<0.0001). Overall times from puncture to final recanalization were reduced from 68.2 to 37 min, also a statistically significant difference (p<0.001). There were no cases of intraprocedural complications such as wire perforation or subarachnoid hemorrhage. CONCLUSIONS: A standardized approach to the equipment used and process for ELVO cases at a single institution can dramatically reduce procedure times. PMID- 27402860 TI - Electron Microscopic Findings Are an Important Aid for Diagnosing Mitochondrial Cardiomyopathy With Mitochondrial DNA Mutation 3243A>G. PMID- 27402861 TI - Myocardial Recovery in Patients Receiving Contemporary Left Ventricular Assist Devices: Results From the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). AB - BACKGROUND: Time course and predictors of myocardial recovery on contemporary left ventricular assist device support are poorly defined because of limited number of recovery patients at any implanting center. This study sought to investigate myocardial recovery using multicenter data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). METHODS AND RESULTS: Thirteen thousand four hundred fifty-four adult patients were studied. Device explant rates for myocardial recovery were 0.9% at 1-year, 1.9% at 2-year, and 3.1% at 3-year follow-up. Independent predictors of device explantation for recovery were age <50 years (odds ratio [OR] 2.5), nonischemic etiology (OR 5.4), time since initial diagnosis <2 years (OR 3.4), suboptimal heart failure therapy before implant (OR 2.2), left ventricular end-diastolic diameter <6.5 cm (OR 1.7), pulmonary systolic artery pressure <50 mm Hg (OR 2.0), blood urea nitrogen <30 mg/dL (OR 3.3), and axial-flow device (OR 7.6). Patients with myocarditis (7.7%), postpartum cardiomyopathy (4.4%), and adriamycin-induced cardiomyopathy (4.1%) had highest rates of device explantation for recovery. Use of neurohormonal blockers on left ventricular assist device support was significantly higher in patients who were explanted for recovery. Importantly, 9% of all left ventricular assist device patients who were not explanted for recovery have demonstrated substantial improvement in left ventricular ejection fraction (partial recovery) and had remarkable overlap in clinical characteristic profile compared with patients who were explanted for recovery (complete recovery). Complete and partial recovery rates have declined in parallel with recent changes observed in device indications and technology. CONCLUSIONS: Myocardial recovery is a spectrum of improvement rather than a binary clinical end point. One in every 10 left ventricular assist device patients demonstrates partial or complete myocardial recovery and should be targeted for functional assessment and optimization. PMID- 27402862 TI - Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila. AB - Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins (hnRNPs) regulates the posttranscriptional fate of RNA during development. Drosophila hnRNP A1, Hrp38, is required for germ line stem cell maintenance and oocyte localization. The mRNA targets regulated by Hrp38 are mostly unknown. We identified 428 Hrp38-associated gene transcripts in the fly ovary, including mRNA of the translational repressor Nanos. We found that Hrp38 binds to the 3' untranslated region (UTR) of Nanos mRNA, which contains a translation control element. We have demonstrated that translation of the luciferase reporter bearing the Nanos 3' UTR is enhanced by dsRNA-mediated Hrp38 knockdown as well as by mutating potential Hrp38-binding sites. Our data show that poly(ADP-ribosyl)ation inhibits Hrp38 binding to the Nanos 3' UTR, increasing the translation in vivo and in vitro hrp38 and Parg null mutants showed an increased ectopic Nanos translation early in the embryo. We conclude that Hrp38 represses Nanos translation, whereas its poly(ADP-ribosyl)ation relieves the repression effect, allowing restricted Nanos expression in the posterior germ plasm during oogenesis and early embryogenesis. PMID- 27402863 TI - Chromatin and Epigenetics at the Forefront: Finding Clues among Peaks. AB - The Keystone Symposium on Chromatin and Epigenetics, organized by Luciano Di Croce (Center for Genomic Regulation, Spain) and Yang Shi (Harvard Medical School, USA), took place 20 to 24 March 2016 at Whistler (British Columbia, Canada). The symposium brought together some of the most outstanding scientists studying how chromatin structure and epigenetic mechanisms regulate gene function in both development and disease. Junior scientists had the opportunity to interact with experienced researchers by presenting their work and discussing ideas and novel hypotheses. In order to foster interaction and networking, the scientific agenda was balanced with an extended social agenda. This meeting review describes several of the most provocative and exciting talks from the symposium, revealing how fast this research field is evolving and the profound impact it will have on human health. PMID- 27402864 TI - Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2. AB - Phenotypic plasticity involves a process in which cells transiently acquire phenotypic traits of another lineage. Two commonly studied types of phenotypic plasticity are epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). In carcinomas, EMT drives invasion and metastatic dissemination, while MET is proposed to play a role in metastatic colonization. Phenotypic plasticity in sarcomas is not well studied; however, there is evidence that a subset of sarcomas undergo an MET-like phenomenon. While the exact mechanisms by which these transitions occur remain largely unknown, it is likely that some of the same master regulators that drive EMT and MET in carcinomas also act in sarcomas. In this study, we combined mathematical models with bench experiments to identify a core regulatory circuit that controls MET in sarcomas. This circuit comprises the microRNA 200 (miR-200) family, ZEB1, and GRHL2. Interestingly, combined expression of miR-200s and GRHL2 further upregulates epithelial genes to induce MET. This effect is phenocopied by downregulation of either ZEB1 or the ZEB1 cofactor, BRG1. In addition, an MET gene expression signature is prognostic for improved overall survival in sarcoma patients. Together, our results suggest that a miR-200, ZEB1, GRHL2 gene regulatory network may drive sarcoma cells to a more epithelial-like state and that this likely has prognostic relevance. PMID- 27402865 TI - Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation. AB - Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442-29456, 2012, http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation in Ada3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation. PMID- 27402866 TI - NF2 Activates Hippo Signaling and Promotes Ischemia/Reperfusion Injury in the Heart. AB - RATIONALE: NF2 (neurofibromin 2) is an established tumor suppressor that promotes apoptosis and inhibits growth in a variety of cell types, yet its function in cardiomyocytes remains largely unknown. OBJECTIVE: We sought to determine the role of NF2 in cardiomyocyte apoptosis and ischemia/reperfusion (I/R) injury in the heart. METHODS AND RESULTS: We investigated the function of NF2 in isolated cardiomyocytes and mouse myocardium at baseline and in response to oxidative stress. NF2 was activated in cardiomyocytes subjected to H2O2 and in murine hearts subjected to I/R. Increased NF2 expression promoted the activation of Mst1 (mammalian sterile 20-like kinase 1) and the inhibition of Yap (Yes-associated protein), whereas knockdown of NF2 attenuated these responses after oxidative stress. NF2 increased the apoptosis of cardiomyocytes that appeared dependent on Mst1 activity. Mice deficient for NF2 in cardiomyocytes, NF2 cardiomyocyte specific knockout (CKO), were protected against global I/R ex vivo and showed improved cardiac functional recovery. Moreover, NF2 cardiomyocyte-specific knockout mice were protected against I/R injury in vivo and showed the upregulation of Yap target gene expression. Mechanistically, we observed nuclear association between NF2 and its activator MYPT-1 (myosin phosphatase target subunit 1) in cardiomyocytes, and a subpopulation of stress-induced nuclear Mst1 was diminished in NF2 CKO hearts. Finally, mice deficient for both NF2 and Yap failed to show protection against I/R indicating that Yap is an important target of NF2 in the adult heart. CONCLUSIONS: NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through the activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart. PMID- 27402867 TI - Sequence determinants spanning -35 motif and AT-rich spacer region impacting Ehrlichia chaffeensis Sigma 70-dependent promoter activity of two differentially expressed p28 outer membrane protein genes. AB - Ehrlichia chaffeensis is an obligate intracellular tick-borne bacterium which causes the disease, human monocytic ehrlichiosis. Ehrlichia chaffeensis contains only two sigma factors, sigma32 and sigma70 It is difficult to study E. chaffeensis gene regulation due to lack of a transformation system. We developed an Escherichia coli-based transcription system to study E. chaffeensis transcriptional regulation. An E. coli strain with its sigma70 repressed with trp promoter is used to express E. chaffeensis sigma70 The E. coli system and our previously established in vitro transcription system were used to map transcriptional differences of two Ehrlichia genes encoding p28-outer membrane proteins 14 and 19. We mapped the -10 and -35 motifs and the AT rich spacers located between the two motifs by performing detailed mutational analysis. Mutations within the -35 motif of the genes impacted transcription differently, while -10 motif deletions had no impact. The AT-rich spacers also contributed to transcriptional differences. We further demonstrated that the domain 4.2 of E. chaffeensis sigma70 is important for regulating promoter activity and the deletion of region 1.1 of E. chaffeensis sigma70 causes enhancement of the promoter activity. This is the first study defining the promoters of two closely related E. chaffeensis genes. PMID- 27402869 TI - l-Carnitine affects preimplantation embryo development toward infertility in mice. AB - l-Carnitine (l-Cn), despite the beneficial role as energy-generating substance delivering long-chain fatty acids to the beta-oxidation pathway in mitochondria, has been accused to cause an endometriosis-like state to BALB/c mice manifested by increased inflammatory cytokines in serum and peritoneal fluid, accumulation of immune cells in the peritoneal cavity and uterine walls and most importantly, correlating to infertility. Exploring this type of infertility, the effect of l Cn on preimplantation embryo development, ovarian integrity and systemic maternal immunity was studied. Using nonlinear microscopy analysis, which was shown to be a powerful tool for determining embryo quality by quantitatively estimating the lipid body (LB) content of the cells, it was shown that in vitro and in vivo administration of l-Cn significantly decreased LB mean area in zygotes. Daily intraperitoneal administration of 2.5mg l-Cn for 3, 4 and 7days to mice significantly decreased the percent of normal zygotes. However, only the 7-day treatment persisted by affecting 2- and 8-cell stage embryos, while almost abolishing blastocyst development. Such effects were accompanied by abnormal ovarian histology, showing increased numbers of corpora luteus and elevated progesterone concentration in the serum. In addition, it was shown that the 7-day l-Cn treatment pushed maternal systemic immunity toward inflammation and immunosuppression by increasing CD11b-, CD25- and CD11bGr1-positive cells in spleen, which opposed the necessity for immunostimulation at these early stages of pregnancy. In conclusion, the results presented here demonstrated that elevated doses of l-Cn affect early stages of embryo development, leading to infertility. PMID- 27402868 TI - Identification of Winter-Responsive Proteins in Bread Wheat Using Proteomics Analysis and Virus-Induced Gene Silencing (VIGS). AB - Proteomic approaches were applied to identify protein spots involved in cold responses in wheat. By comparing the differentially accumulated proteins from two cultivars (UC1110 and PI 610750) and their derivatives, as well as the F10 recombinant inbred line population differing in cold-tolerance, a total of 20 common protein spots representing 16 unique proteins were successfully identified using 2-DE method. Of these, 14 spots had significantly enhanced abundance in the cold-sensitive parental cultivar UC1110 and its 20 descendant lines when compared with the cold-tolerant parental cultivar PI 610750 and its 20 descendant lines. Six protein spots with reduced abundance were also detected. The identified protein spots are involved in stress/defense, carbohydrate metabolism, protein metabolism, nitrogen metabolism, energy metabolism, and photosynthesis. The 20 differentially expressed protein spots were chosen for quantitative real-time polymerase chain reaction (qRT-PCR) to investigate expression changes at the RNA level. The results indicated that the transcriptional expression patterns of 11 genes were consistent with their protein expression models. Among the three unknown proteins, Spot 20 (PAP6-like) showed high sequence similarities with PAP6. qRT-PCR results implied that cold and salt stresses increased the expression of PAP6-like in wheat leaves. Furthermore, VIGS (virus-induced gene silencing)-treated plants generated for PAP6-like were subjected to freezing stress, these plants had more serious droop and wilt, an increased rate of relative electrolyte leakage, reduced relative water content (RWC) and decreased tocopherol levels when compared with viral control plants. However, the plants that were silenced for the other two unknown proteins had no significant differences in comparison to the BSMV0-inoculated plants under freezing conditions. These results indicate that PAP6-like possibly plays an important role in conferring cold tolerance in wheat. PMID- 27402870 TI - Early detection of hearing impairment reflected in better reading ability in teenage years. PMID- 27402871 TI - Smoking cessation improves Crohn's disease outcomes regardless of the use of anti TNF or immunomodulator. PMID- 27402872 TI - T cell co-stimulatory factors. PMID- 27402873 TI - Validation of disease activity indices using the 28 joint counts in systemic sclerosis. AB - OBJECTIVES: To validate the Disease Activity Score 28 using ESR (DAS28-ESR) and CRP (DAS28-CRP), the Simplified Disease Activity Index and the Clinical Disease Activity Index used in RA for SSc patients. METHODS: Seventy-seven SSc patients, 40 RA patients, 20 patients with primary RP (PRP) and 28 healthy volunteers were assessed. Besides the disease activity composite indices, the European Scleroderma Study Group Activity Index (EScSG-AI), the HAQ-DI, the Cochin Hand Function Scale and the Short Form Health Survey (SF36) were evaluated. The validation procedure included the assessment for truth, discrimination and feasibility. RESULTS: DAS28-ESR, DAS28-CRP, Simplified Disease Activity Index and Clinical Disease Activity Index showed significant correlation with EScSG-AI, HAQ DI, Cochin Hand Function Scale and the physical component of SF36 (P < 0.001). All four indices discriminated patients with SSc from RA, PRS and healthy controls, respectively (P < 0.01). With the exception of DAS28-CRP, the other three indices also discriminated between subgroups of SSc based on value of EScSG AI (?3 and >3) (P < 0.05). All four disease activity composite indices showed a good inter- and intraobserver reliability based on repeated measures of two independent investigators (P < 0.001). CONCLUSION: All four disease activity composite indices were found to be valid measures for assessing arthritis in SSc. DAS28-ESR showed the best performance regarding reliability and construct validity. PMID- 27402874 TI - Recent developments in the treatment of anxiety disorders in children and adolescents. AB - Anxiety disorders are among the most common emotional difficulties experienced by children and young people. They cause significant disturbance to the lives of young people and their families and present a risk for lifelong psychological disturbance. Effective psychological (ie, cognitive-behaviour therapy (CBT)) and pharmacological interventions (eg, selective serotonin reuptake inhibitors (SSRIs)) have been established. However, the risk of adverse effects and unknown long-term effects of using SSRIs has led to recommendations that CBT is delivered as a first-line intervention. Recent innovations have included the development of low-intensity CBT programmes, delivered briefly via parents or online. These hold promise to increase access to psychological therapies for children and young people with these common and severe difficulties. PMID- 27402875 TI - Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo. AB - The aim of this study was to investigate the direct muscle cell-mediated actions of androgens by comparing two different mouse lines. The cre-loxP system was used to delete the DNA-binding activity of the androgen receptor (AR) in mature myofibers (MCK mAR(DeltaZF2)) in one model and the DNA-binding activity of the AR in both proliferating myoblasts and myofibers (alpha-actin mAR(DeltaZF2)) in another model. We found that hind-limb muscle mass was normal in MCK mAR(DeltaZF2) mice and that relative mass of only some hind-limb muscles was reduced in alpha-actin mAR(DeltaZF2) mice. This suggests that myoblasts and myofibers are not the major cellular targets mediating the anabolic actions of androgens on male muscle during growth and development. Levator ani muscle mass was decreased in both mouse lines, demonstrating that there is a myofiber specific effect in this unique androgen-dependent muscle. We found that the pattern of expression of genes including c-myc, Fzd4 and Igf2 is associated with androgen-dependent changes in muscle mass; therefore, these genes are likely to be mediators of anabolic actions of androgens. Further research is required to identify the major targets of androgen actions in muscle, which are likely to include indirect actions via other tissues. PMID- 27402877 TI - Identification of genetic modifiers of age-at-onset for familial Parkinson's disease. AB - Parkinson's disease (PD) is the most common cause of neurodegenerative movement disorder and the second most common cause of dementia. Genes are thought to have a stronger effect on age-at-onset of PD than on risk, yet there has been a phenomenal success in identifying risk loci but not age-at-onset modifiers. We conducted a genome-wide study for age-at-onset. We analysed familial and non familial PD separately, per prior evidence for strong genetic effect on age-at onset in familial PD. GWAS was conducted in 431 unrelated PD individuals with at least one affected relative (familial PD) and 1544 non-familial PD from the NeuroGenetics Research Consortium (NGRC); an additional 737 familial PD and 2363 non-familial PD were used for replication. In familial PD, two signals were detected and replicated robustly: one mapped to LHFPL2 on 5q14.1 (PNGRC = 3E-8, PReplication = 2E-5, PNGRC + Replication = 1E-11), the second mapped to TPM1 on 15q22.2 (PNGRC = 8E-9, PReplication = 2E-4, PNGRC + Replication = 9E-11). The variants that were associated with accelerated onset had low frequencies (<0.02). The LHFPL2 variant was associated with earlier onset by 12.33 [95% CI: 6.2; 18.45] years in NGRC, 8.03 [2.95; 13.11] years in replication, and 9.79 [5.88; 13.70] years in the combined data. The TPM1 variant was associated with earlier onset by 15.30 [8.10; 22.49] years in NGRC, 9.29 [1.79; 16.79] years in replication, and 12.42 [7.23; 17.61] years in the combined data. Neither LHFPL2 nor TPM1 was associated with age-at-onset in non-familial PD. LHFPL2 (function unknown) is overexpressed in brain tumours. TPM1 encodes a highly conserved protein that regulates muscle contraction, and is a tumour-suppressor gene. PMID- 27402878 TI - Proteomics to study DNA-bound and chromatin-associated gene regulatory complexes. AB - High-resolution mass spectrometry (MS)-based proteomics is a powerful method for the identification of soluble protein complexes and large-scale affinity purification screens can decode entire protein interaction networks. In contrast, protein complexes residing on chromatin have been much more challenging, because they are difficult to purify and often of very low abundance. However, this is changing due to recent methodological and technological advances in proteomics. Proteins interacting with chromatin marks can directly be identified by pulldowns with synthesized histone tails containing posttranslational modifications (PTMs). Similarly, pulldowns with DNA baits harbouring single nucleotide polymorphisms or DNA modifications reveal the impact of those DNA alterations on the recruitment of transcription factors. Accurate quantitation - either isotope-based or label free - unambiguously pinpoints proteins that are significantly enriched over control pulldowns. In addition, protocols that combine classical chromatin immunoprecipitation (ChIP) methods with mass spectrometry (ChIP-MS) target gene regulatory complexes in their in-vivo context. Similar to classical ChIP, cells are crosslinked with formaldehyde and chromatin sheared by sonication or nuclease digested. ChIP-MS baits can be proteins in tagged or endogenous form, histone PTMs, or lncRNAs. Locus-specific ChIP-MS methods would allow direct purification of a single genomic locus and the proteins associated with it. There, loci can be targeted either by artificial DNA-binding sites and corresponding binding proteins or via proteins with sequence specificity such as TAL or nuclease deficient Cas9 in combination with a specific guide RNA. We predict that advances in MS technology will soon make such approaches generally applicable tools in epigenetics. PMID- 27402879 TI - Parent-of-origin tumourigenesis is mediated by an essential imprinted modifier in SDHD-linked paragangliomas: SLC22A18 and CDKN1C are candidate tumour modifiers. AB - Mutations in SDHD and SDHAF2 (both located on chromosome 11) give rise to hereditary paraganglioma almost exclusively after paternal transmission of the mutation, and tumours often show loss of the entire maternal copy of chromosome 11. The 'Hensen' model postulates that a tumour modifier gene located on chromosome 11p15, a region known to harbour a cluster of imprinted genes, is essential to tumour formation. We observed decreased protein expression of the 11p15 candidate genes CDKN1C, SLC22A18 and ZNF215 evaluated in 60 SDHD-mutated tumours compared to normal carotid body tissue and non-SDH mutant tumours.We then created stable knockdown in vitro models, reasoning that the simultaneous knockdown of SDHD and a maternally expressed 11p15 modifier gene would enhance paraganglioma-related cellular characteristics compared to SDHD knockdown alone. Knockdown of SDHD in SNB19 and SHSY5Y cells resulted in the accumulation of succinate, the stabilization of HIF1 protein and a reduction in cell proliferation.Compared to single knockdown of SDHD, knockdown of SDHD together with SLC22A18 or with CDKN1C led to small but significant increases in cell proliferation and resistance to apoptosis, and to a gene expression profile closely related to the known transcriptional profile of SDH-deficient tumours. Of the 60 SDHD tumours investigated, four tumours showing retention of chromosome 11 showed SLC22A18 and CDKN1C expression levels comparable to levels in tumours showing loss of chromosome 11, suggesting loss of protein expression despite chromosomal retention.Our data strongly suggest that SLC22A18 and/or CDKN1C are tumour modifier genes involved in the tumourigenesis of SDHD-linked paraganglioma. PMID- 27402880 TI - Calcium dynamics change in degenerating cone photoreceptors. AB - Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies suggest a central role for calcium (Ca2+) homeostasis deficits in photoreceptor degeneration; however, direct evidence for this is scarce and physiological measurements of Ca2+ in degenerating mammalian cones are lacking.Here, we took advantage of the transgenic HR2.1:TN-XL mouse line that expresses a genetically encoded Ca2+ biosensor exclusively in cones. We cross-bred this line with mouse models for primary ("cone photoreceptor function loss-1", cpfl1) and secondary ("retinal degeneration-1", rd1) cone degeneration, respectively, and assessed resting Ca2+ levels and light-evoked Ca2+ responses in cones using two-photon imaging. We found that Ca2+ dynamics were altered in cpfl1 cones, showing higher noise and variable Ca2+ levels, with significantly wider distribution than for wild-type and rd1 cones. Unexpectedly, up to 21% of cpfl1 cones still displayed light-evoked Ca2+ responses, which were larger and slower than wild-type responses. In contrast, genetically intact rd1 cones were characterized by lower noise and complete lack of visual function.Our study demonstrates alterations in cone Ca2+ dynamics in both primary and secondary cone degeneration. Our results are consistent with the view that higher (fluctuating) cone Ca2+ levels are involved in photoreceptor cell death in primary (cpfl1) but not in secondary (rd1) cone degeneration. These findings may guide the future development of therapies targeting photoreceptor Ca2+ homeostasis. PMID- 27402881 TI - Identification and function of enhancers in the human genome. AB - The study of gene regulation has rapidly advanced by leveraging next-generation sequencing to identify and characterize the cis and trans elements that are critical for defining cell identity. These advances have paralleled a movement towards whole genome sequencing in clinics. These two tracks have increasingly synergized to underscore the importance of cis-regulatory elements in development as well produce countless studies implicating these elements in human disease. Other studies have emphasized the clinical phenotypes associated with variation or mutations in trans factors, including non-coding RNAs and chromatin regulators. These studies highlight the importance of obtaining a comprehensive understanding of mammalian gene regulation for predicting the impact of genetic variation on patient phenotypes. Currently lagging behind the generation of vast datasets and annotations is our ability to examine these putative elements in the dynamic context of a developing organism. PMID- 27402883 TI - A definition and ethical evaluation of overdiagnosis. AB - Overdiagnosis is an emerging problem in health policy and practice: we address its definition and ethical implications. We argue that the definition of overdiagnosis should be expressed at the level of populations. Consider a condition prevalent in a population, customarily labelled with diagnosis A. We propose that overdiagnosis is occurring in respect of that condition in that population when (1) the condition is being identified and labelled with diagnosis A in that population (consequent interventions may also be offered); (2) this identification and labelling would be accepted as correct in a relevant professional community; but (3) the resulting label and/or intervention carries an unfavourable balance between benefits and harms. We identify challenges in determining and weighting relevant harms, then propose three central ethical considerations in overdiagnosis: the extent of harm done, whether harm is avoidable and whether the primary goal of the actor/s concerned is to benefit themselves or the patient, citizen or society. This distinguishes predatory (avoidable, self-benefiting), misdirected (avoidable, other-benefiting) and tragic (unavoidable, other-benefiting) overdiagnosis; the degree of harm moderates the justifiability of each type. We end with four normative challenges: (1) methods for adjudicating between professional standards and identifying relevant harms and benefits should be procedurally just; (2) individuals, organisations and states are differently responsible for addressing overdiagnosis; (3) overdiagnosis is a matter for distributive justice: the burdens of both overdiagnosis and its prevention could fall on the least-well off; and (4) communicating about overdiagnosis risks harming those unaware that they may have been overdiagnosed. These challenges will need to be addressed as the field develops. PMID- 27402884 TI - Is it acceptable for medical professionals to kiss paediatric patients? AB - It is human nature, perhaps more so for doctors and nurses, to comfort children in distress. Unfortunately, however, necessary medical procedures carried out by healthcare providers (eg, venipuncture) can often result in pain and discomfort, which may in turn cause the provider a degree of guilt and distress. Is it ever acceptable to comfort a paediatric patient with a kiss? This essay examines the literature published on this subject reflecting on a recent encounter with a patient. PMID- 27402882 TI - Loss-of-function mutations in the SIGMAR1 gene cause distal hereditary motor neuropathy by impairing ER-mitochondria tethering and Ca2+ signalling. AB - Distal hereditary motor neuropathies (dHMNs) are clinically and genetically heterogeneous neurological conditions characterized by degeneration of the lower motor neurons. So far, 18 dHMN genes have been identified, however, about 80% of dHMN cases remain without a molecular diagnosis. By a combination of autozygosity mapping, identity-by-descent segment detection and whole-exome sequencing approaches, we identified two novel homozygous mutations in the SIGMAR1 gene (p.E138Q and p.E150K) in two distinct Italian families affected by an autosomal recessive form of HMN. Functional analyses in several neuronal cell lines strongly support the pathogenicity of the mutations and provide insights into the underlying pathomechanisms involving the regulation of ER-mitochondria tethering, Ca2+ homeostasis and autophagy. Indeed, in vitro, both mutations reduce cell viability, the formation of abnormal protein aggregates preventing the correct targeting of sigma-1R protein to the mitochondria-associated ER membrane (MAM) and thus impinging on the global Ca2+ signalling. Our data definitively demonstrate the involvement of SIGMAR1 in motor neuron maintenance and survival by correlating, for the first time in the Caucasian population, mutations in this gene to distal motor dysfunction and highlight the chaperone activity of sigma-1R at the MAM as a critical aspect in dHMN pathology. PMID- 27402876 TI - An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression. AB - Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERalpha-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERalpha binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95%CI 0.55-0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 * 10 19) and identify 13 additional linked variants (r2 > 0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 * 10-15 - 5.6 * 10-17). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5. PMID- 27402885 TI - It started with a kiss. PMID- 27402886 TI - A libertarian case for mandatory vaccination. AB - This paper argues that mandatory, government-enforced vaccination can be justified even within a libertarian political framework. If so, this implies that the case for mandatory vaccination is very strong indeed as it can be justified even within a framework that, at first glance, loads the philosophical dice against that conclusion. I argue that people who refuse vaccinations violate the 'clean hands principle', a (in this case, enforceable) moral principle that prohibits people from participating in the collective imposition of unjust harm or risk of harm. In a libertarian framework, individuals may be forced to accept certain vaccines not because they have an enforceable duty to serve the common, and not because cost-benefit analysis recommends it, but because anti-vaxxers are wrongfully imposing undue harm upon others. PMID- 27402887 TI - The social value of candidate HIV cures: actualism versus possibilism. AB - A sterilising or functional cure for HIV is a serious scientific challenge but presents a viable pathway to the eradication of HIV. Such an event would be extremely valuable in terms of relieving the burden of a terrible disease; however, a coordinated commitment to implement healthcare interventions, particularly in regions that bear the brunt of the HIV epidemic, is lacking. In this paper, we examine two strategies for evaluating candidate HIV cures, based on our beliefs about the likelihood of global implementation. We reject possibilist interpretations of social value that do not account for the likelihood that a plan to cure HIV will be followed through. We argue, instead, for an actualist ranking of options for action, which accounts for the likelihood that a cure will be low cost, scalable and easy to administer worldwide. PMID- 27402889 TI - Neuroimaging overuse is more common in Medicare compared with the VA. AB - OBJECTIVE: To inform initiatives to reduce overuse, we compared neuroimaging appropriateness in a large Medicare cohort with a Department of Veterans Affairs (VA) cohort. METHODS: Separate retrospective cohorts were established in Medicare and in VA for headache and neuropathy from 2004 to 2011. The Medicare cohorts included all patients enrolled in the Health and Retirement Study (HRS) with linked Medicare claims (HRS-Medicare; n = 1,244 for headache and 998 for neuropathy). The VA cohorts included all patients receiving services in the VA (n = 93,755 for headache and 183,642 for neuropathy). Inclusion criteria were age over 65 years and an outpatient visit for incident neuropathy or a primary headache. Neuroimaging use was measured with Current Procedural Terminology codes and potential overuse was defined using published criteria for use with administrative data. Increasingly specific appropriateness criteria excluded nontarget conditions for which neuroimaging may be appropriate. RESULTS: For both peripheral neuropathy and headache, potentially inappropriate imaging was more common in HRS-Medicare compared with the VA. Forty-nine percentage of all headache patients received neuroimaging in HRS-Medicare compared with 22.1% in the VA (p < 0.001) and differences persist when analyzing more specific definitions of overuse. A total of 23.7% of all HRS-Medicare incident neuropathy patients received neuroimaging compared with 9.0% in the VA (p < 0.001), and the difference persisted after excluding nontarget conditions. CONCLUSIONS: Overuse of neuroimaging is likely less common in the VA than in a Medicare population. Better understanding the reasons for the more selective use of neuroimaging in the VA could help inform future initiatives to reduce overuse of diagnostic testing. PMID- 27402888 TI - Composition and Genetic Diversity of Mosquitoes (Diptera: Culicidae) on Islands and Mainland Shores of Kenya's Lakes Victoria and Baringo. AB - The Lake Baringo and Lake Victoria regions of Kenya are associated with high seroprevalence of mosquito-transmitted arboviruses. However, molecular identification of potential mosquito vector species, including morphologically identified ones, remains scarce. To estimate the diversity, abundance, and distribution of mosquito vectors on the mainland shores and adjacent inhabited islands in these regions, we collected and morphologically identified adult and immature mosquitoes and obtained the corresponding sequence variation at cytochrome c oxidase 1 (COI) and internal transcribed spacer region 2 (ITS2) gene regions. A total of 63 species (including five subspecies) were collected from both study areas, 47 of which have previously been implicated as disease vectors. Fourteen species were found only on island sites, which are rarely included in mosquito diversity surveys. We collected more mosquitoes, yet with lower species composition, at Lake Baringo (40,229 mosquitoes, 32 species) than at Lake Victoria (22,393 mosquitoes, 54 species). Phylogenetic analysis of COI gene sequences revealed Culex perexiguus and Cx tenagius that could not be distinguished morphologically. Most Culex species clustered into a heterogeneous clade with closely related sequences, while Culex pipiens clustered into two distinct COI and ITS2 clades. These data suggest limitations in current morphological identification keys. This is the first DNA barcode report of Kenyan mosquitoes. To improve mosquito species identification, morphological identifications should be supported by their molecular data, while diversity surveys should target both adults and immatures. The diversity of native mosquito disease vectors identified in this study impacts disease transmission risks to humans and livestock. PMID- 27402892 TI - ALS and physician-assisted suicide. PMID- 27402891 TI - Development and validation of the Myasthenia Gravis Impairment Index. AB - OBJECTIVE: We aimed to develop a measure of myasthenia gravis impairment using a previously developed framework and to evaluate reliability and validity, specifically face, content, and construct validity. METHODS: The first draft of the Myasthenia Gravis Impairment Index (MGII) included examination items from available measures enriched with newly developed, patient-reported items, modified after patient input. International neuromuscular specialists evaluated face and content validity via an e-mail survey. Test-retest reliability was assessed in stable patients at a 3-week interval and interrater reliability was evaluated in the same day. Construct validity was assessed through correlations between the MGII and other measures and by comparing scores in different patient groups. RESULTS: The first draft was assessed by 18 patients, and 72 specialists answered the survey. The second draft had 7 examination and 22 patient-reported items. Field testing included 200 patients, with 54 patients completing the reliability studies. Test-retest reliability of the total score was good (intraclass correlation coefficient 0.92; 95% confidence interval 0.79-0.94), as was interrater reliability of the examination component (intraclass correlation coefficient 0.81; 95% confidence interval 0.79-0.94). The MGII correlated well with comparison measures, with higher correlations with the MG-activities of daily living (r = 0.91) and MG-specific quality of life 15-item scale (r = 0.78). When assessing different patient groups, the scores followed expected patterns. CONCLUSIONS: The MGII was developed using a patient-centered framework of myasthenia-related impairments and incorporating patient input throughout the development process. It is reliable in an outpatient setting and has demonstrated construct validity. Responsiveness studies are under way. PMID- 27402893 TI - Neurologic features in intermediate allele carriers of Huntington disease. PMID- 27402894 TI - Dementia risk with antihypertensive use and blood pressure variability: A cohort study. AB - OBJECTIVE: To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability (BPV) in the preceding 4 years. METHODS: A total of 6,537 participants (mean age 79 years, 62% women) in a prospective population-based cohort were followed up for incident dementia. A 4-year time lag period was created to classify drug exposure and measure blood pressure. BPV (percent coefficient of variation [CV]) was regressed against 9 antihypertensive drug classes (BPVreg). Cox regression models were employed to determine hazard ratios (HRs) for incident dementia thereafter according to drug class, adjusted for mean blood pressure, covariates, and BPV or BPVreg. RESULTS: Over a median 8.4 years follow-up (interquartile range 6.7-9.0), lower dementia risk was associated with nondihydropyridine calcium channel blocker (HR 0.56; 95% confidence interval [CI] 0.31-1.00, p = 0.05) and loop diuretics (HR 0.45; 95% CI 0.22-0.93, p = 0.03) after adjusting for CV-BPV. Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker (HR 0.52; 95% CI 0.28-0.95, p = 0.03) and loop diuretics (HR 0.40; 95% CI 0.19-0.83, p = 0.01). All systolic BPV * antihypertensive drug interaction terms were not different from p < 0.05. CONCLUSIONS: Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years. Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk. PMID- 27402896 TI - Using disease-specific, patient-reported measures in everyday clinic. PMID- 27402895 TI - Motor cortical function determines prognosis in sporadic ALS. AB - OBJECTIVE: To study the relationship between cortical function and survival in amyotrophic lateral sclerosis (ALS). METHODS: A total of 216 referrals were screened, and participants with familial ALS or an inexcitable cortex were excluded. Clinical measures and phenotyping from 169 patients with sporadic ALS were combined with an assessment of cortical function using threshold tracking transcranial magnetic stimulation with indices including short interval intracortical inhibition (SICI). Peripheral nerve studies were collected, incorporating compound muscle action potential amplitude. Clinical prognostic factors were recorded longitudinally, including ALS Functional Rating Scale Revised (ALSFRS-R). RESULTS: Compared to 109 healthy controls, 169 patients had reduced SICI (p < 0.0001). In survival analysis, 105 patients progressed to death with an estimated median survival time of 37 months. In patients with less than 2 years disease duration (n = 140), those with bulbar onset (p = 0.017), rapid vital capacity (VC) decline (p < 0.0001), rapid ALSFRS-R decline (p < 0.0001), and reduced averaged SICI (p = 0.047) had a poorer prognosis. Multivariate analysis identified rapid VC decline (p < 0.0001), rapid ALSFRS-R decline (p = 0.0060), and reduced averaged SICI (p = 0.011) as factors independently associated with a shorter survival. CONCLUSIONS: Cortical dysfunction appears to be a prognostic marker in patients with ALS within 2 years of disease onset, such that patients with reduced averaged SICI, indicative of intracortical hyperexcitability, demonstrated a worse prognosis. PMID- 27402897 TI - A computational strategy for the search of regulatory small RNAs in Actinobacillus pleuropneumoniae. AB - Bacterial regulatory small RNAs (sRNAs) play important roles in gene regulation and are frequently connected to the expression of virulence factors in diverse bacteria. Only a few sRNAs have been described for Pasteurellaceae pathogens and no in-depth analysis of sRNAs has been described for Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, responsible for considerable losses in the swine industry. To search for sRNAs in A. pleuropneumoniae, we developed a strategy for the computational analysis of the bacterial genome by using four algorithms with different approaches, followed by experimental validation. The coding strand and expression of 17 out of 23 RNA candidates were confirmed by Northern blotting, RT-PCR, and RNA sequencing. Among them, two are likely riboswitches, three are housekeeping regulatory RNAs, two are the widely studied GcvB and 6S sRNAs, and 10 are putative novel trans-acting sRNAs, never before described for any bacteria. The latter group has several potential mRNA targets, many of which are involved with virulence, stress resistance, or metabolism, and connect the sRNAs in a complex gene regulatory network. The sRNAs identified are well conserved among the Pasteurellaceae that are evolutionarily closer to A. pleuropneumoniae and/or share the same host. Our results show that the combination of newly developed computational programs can be successfully utilized for the discovery of novel sRNAs and indicate an intricate system of gene regulation through sRNAs in A. pleuropneumoniae and in other Pasteurellaceae, thus providing clues for novel aspects of virulence that will be explored in further studies. PMID- 27402898 TI - Relative contributions of the structural and catalytic roles of Rrp6 in exosomal degradation of individual mRNAs. AB - The RNA exosome is a conserved complex for RNA degradation with two ribonucleolytic subunits, Dis3 and Rrp6. Rrp6 is a 3'-5' exonuclease, but it also has a structural role in helping target RNAs to the Dis3 activity. The relative importance of the exonuclease activity and the targeting activity probably differs between different RNA substrates, but this is poorly understood. To understand the relative contributions of the exonuclease and the targeting activities to the degradation of individual RNA substrates in Schizosaccharomyces pombe, we compared RNA levels in an rrp6 null mutant to those in an rrp6 point mutant specifically defective in exonuclease activity. A wide range of effects was found, with some RNAs dependent mainly on the structural role of Rrp6 ("protein-dependent" targets), other RNAs dependent mainly on the catalytic role ("activity-dependent" targets), and some RNAs dependent on both. Some protein dependent RNAs contained motifs targeted via the RNA-binding protein Mmi1, while others contained a motif possibly involved in response to iron. In these and other cases Rrp6 may act as a structural adapter to target specific RNAs to the exosome by interacting with sequence-specific RNA-binding proteins. PMID- 27402900 TI - samExploreR: exploring reproducibility and robustness of RNA-seq results based on SAM files. AB - MOTIVATION: Data from RNA-seq experiments provide us with many new possibilities to gain insights into biological and disease mechanisms of cellular functioning. However, the reproducibility and robustness of RNA-seq data analysis results is often unclear. This is in part attributed to the two counter acting goals of (i) a cost efficient and (ii) an optimal experimental design leading to a compromise, e.g. in the sequencing depth of experiments. RESULTS: We introduce an R package called samExploreR that allows the subsampling (m out of n bootstraping) of short reads based on SAM files facilitating the investigation of sequencing depth related questions for the experimental design. Overall, this provides a systematic way for exploring the reproducibility and robustness of general RNA seq studies. We exemplify the usage of samExploreR by studying the influence of the sequencing depth and the annotation on the identification of differentially expressed genes. AVAILABILITY AND IMPLEMENTATION: samExploreR is available as an R package from Bioconductor. CONTACT: v@bio-complexity.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27402899 TI - Purification and analysis of endogenous human RNA exosome complexes. AB - As a result of its importance in key RNA metabolic processes, the ribonucleolytic RNA exosome complex has been the focus of intense study for almost two decades. Research on exosome subunit assembly, cofactor and substrate interaction, enzymatic catalysis and structure have largely been conducted using complexes produced in the yeast Saccharomyces cerevisiae or in bacteria. Here, we examine different populations of endogenous exosomes from human embryonic kidney (HEK) 293 cells and test their enzymatic activity and structural integrity. We describe methods to prepare EXOSC10-containing, enzymatically active endogenous human exosomes at suitable yield and purity for in vitro biochemistry and negative stain transmission electron microscopy. This opens the door for assays designed to test the in vitro effects of putative cofactors on human exosome activity and will enable structural studies of preparations from endogenous sources. PMID- 27402901 TI - A subpopulation model to analyze heterogeneous cell differentiation dynamics. AB - MOTIVATION: Cell differentiation is steered by extracellular signals that activate a cell type specific transcriptional program. Molecular mechanisms that drive the differentiation can be analyzed by combining mathematical modeling with population average data. For standard mathematical models, the population average data is informative only if the measurements come from a homogeneous cell culture. In practice, however, the differentiation efficiencies are always imperfect. Consequently, cell cultures are inherently mixtures of several cell types, which have different molecular mechanisms and exhibit quantitatively different dynamics. There is an urgent need for data-driven mathematical modeling approaches that can detect possible heterogeneity and, further, recover the molecular mechanisms from heterogeneous data. RESULTS: We develop a novel method that models a heterogeneous population using homogeneous subpopulations that evolve in parallel. Different subpopulations can represent different cell types and each subpopulation can have cell type specific molecular mechanisms. We present statistical methodology that can be used to quantify the effect of heterogeneity and to infer the subpopulation specific molecular interactions. After a proof of principle study with simulated data, we apply our methodology to analyze the differentiation of human Th17 cells using time-course RNA sequencing data. We construct putative molecular networks driving the T cell activation and Th17 differentiation and allow the cell populations to be split into two subpopulations in the case of heterogeneous samples. Our analysis shows that the heterogeneity indeed has a statistically significant effect on observed dynamics and, furthermore, our statistical methodology can infer both the subpopulation specific molecular mechanisms and the effect of heterogeneity. AVAILABILITY AND IMPLEMENTATION: An implementation of the method is available at http://research.ics.aalto.fi/csb/software/subpop/ CONTACT: jukka.intosalmi@aalto.fi or harri.lahdesmaki@aalto.fiSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27402902 TI - New quality measure for SNP array based CNV detection. AB - MOTIVATION: Only a few large systematic studies have evaluated the impact of copy number variants (CNVs) on common diseases. Several million individuals have been genotyped on single nucleotide variation arrays, which could be used for genome wide CNVs association studies. However, CNV calls remain prone to false positives and only empirical filtering strategies exist in the literature. To overcome this issue, we defined a new quality score (QS) estimating the probability of a CNV called by PennCNV to be confirmed by other software. RESULTS: Out-of-sample comparison showed that the correlation between the consensus CNV status and the QS is twice as high as it is for any previously proposed CNV filters. ROC curves displayed an AUC higher than 0.8 and simulations showed an increase up to 20% in statistical power when using QS in comparison to other filtering strategies. Superior performance was confirmed also for alternative consensus CNV definition and through improving known CNV-trait associations. AVAILABILITY AND IMPLEMENTATION: http://goo.gl/T6yuFM CONTACT: zoltan.kutalik@unil.ch or aurelien@mace@unil.chSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27402903 TI - MIMEAnTo: profiling functional RNA in mutational interference mapping experiments. AB - : The mutational interference mapping experiment (MIME) is a powerful method that, coupled to a bioinformatics analysis pipeline, allows the identification of domains and structures in RNA that are important for its function. In MIME, target RNAs are randomly mutated, selected by function, physically separated and sequenced using next-generation sequencing (NGS). Quantitative effects of each mutation at each position in the RNA can be recovered with statistical certainty using the herein developed user-friendly, cross-platform software MIMEAnTo (MIME Analysis Tool). AVAILABILITY AND IMPLEMENTATION: MIMEAnTo is implemented in C ++ using the boost library as well as Qt for the graphical user interface and is distributed under GPL (http://www.gnu.org/licences/gpl). The libraries are statically linked in a stand alone executable and are not required on the system. The plots are generated with gnuplot. Gnuplot-iostream (https://github.com/dstahlke/gnuplot-iostream) serves as gnuplot interface. Standalone executables including examples and source code can be downloaded from https://github.com/maureensmith/MIMEAnTo CONTACTS: msmith@zedat.fu-berlin.de or vkleist@zedat.fu-berlin.deSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27402904 TI - Towards the knowledge-based design of universal influenza epitope ensemble vaccines. AB - MOTIVATION: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. RESULTS: To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes. AVAILABILITY AND IMPLEMENTATION: http://imed.med.ucm.es/Tools/episopt.html CONTACT: d.r.flower@aston.ac.uk. PMID- 27402905 TI - PyPanda: a Python package for gene regulatory network reconstruction. AB - : PANDA (Passing Attributes between Networks for Data Assimilation) is a gene regulatory network inference method that uses message-passing to integrate multiple sources of 'omics data. PANDA was originally coded in C ++. In this application note we describe PyPanda, the Python version of PANDA. PyPanda runs considerably faster than the C ++ version and includes additional features for network analysis. AVAILABILITY AND IMPLEMENTATION: The open source PyPanda Python package is freely available at http://github.com/davidvi/pypanda CONTACT: mkuijjer@jimmy.harvard.edu or d.g.p.van_ijzendoorn@lumc.nl. PMID- 27402890 TI - Clinical manifestations of intermediate allele carriers in Huntington disease. AB - OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. METHODS: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. RESULTS: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002). CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. CLINICALTRIALSGOV IDENTIFIER: NCT01590589. PMID- 27402906 TI - CRISPR-DO for genome-wide CRISPR design and optimization. AB - MOTIVATION: Despite the growing popularity in using CRISPR/Cas9 technology for genome editing and gene knockout, its performance still relies on well-designed single guide RNAs (sgRNA). In this study, we propose a web application for the Design and Optimization (CRISPR-DO) of guide sequences that target both coding and non-coding regions in spCas9 CRISPR system across human, mouse, zebrafish, fly and worm genomes. CRISPR-DO uses a computational sequence model to predict sgRNA efficiency, and employs a specificity scoring function to evaluate the potential of off-target effect. It also provides information on functional conservation of target sequences, as well as the overlaps with exons, putative regulatory sequences and single-nucleotide polymorphisms (SNPs). The web application has a user-friendly genome-browser interface to facilitate the selection of the best target DNA sequences for experimental design. AVAILABILITY AND IMPLEMENTATION: CRISPR-DO is available at http://cistrome.org/crispr/ CONTACT: qiliu@tongji.edu.cn or hanxu@jimmy.harvard.edu or xsliu@jimmy.harvard.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27402907 TI - BioNetGen 2.2: advances in rule-based modeling. AB - : : BioNetGen is an open-source software package for rule-based modeling of complex biochemical systems. Version 2.2 of the software introduces numerous new features for both model specification and simulation. Here, we report on these additions, discussing how they facilitate the construction, simulation and analysis of larger and more complex models than previously possible. AVAILABILITY AND IMPLEMENTATION: Stable BioNetGen releases (Linux, Mac OS/X and Windows), with documentation, are available at http://bionetgen.org Source code is available at http://github.com/RuleWorld/bionetgen CONTACT: bionetgen.help@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27402908 TI - SYNBADm: a tool for optimization-based automated design of synthetic gene circuits. AB - MOTIVATION: The design of de novo circuits with predefined performance specifications is a challenging problem in Synthetic Biology. Computational models and tools have proved to be crucial for a successful wet lab implementation. Natural gene circuits are complex, subject to evolutionary tradeoffs and playing multiple roles. However, most synthetic designs implemented to date are simple and perform a single task. As the field progresses, advanced computational tools are needed in order to handle greater levels of circuit complexity in a more flexible way and considering multiple design criteria. RESULTS: This works presents SYNBADm (SYNthetic Biology Automated optimal Design in Matlab), a software toolbox for the automatic optimal design of gene circuits with targeted functions from libraries of components. This tool makes use of global optimization to simultaneously search the space of structures and kinetic parameters. SYNBADm can efficiently handle high levels of circuit complexity and can consider multiple design criteria through multiobjective optimization. Further, it provides flexible design capabilities, i.e. the user can define the modeling framework, library of components and target performance function(s). AVAILABILITY AND IMPLEMENTATION: SYNBADm runs under the popular MATLAB computational environment, and is available under GPLv3 license at https://sites.google.com/site/synbadm CONTACT: ireneotero@iim.csic.es or julio@iim.csic.es. PMID- 27402909 TI - Is underage abortion associated with adverse outcomes in early adulthood? A longitudinal birth cohort study up to 25 years of age. AB - STUDY QUESTION: Is underage abortion associated with adverse socioeconomic and health outcomes in early adulthood when compared with underage delivery? SUMMARY ANSWER: Underage abortion was not found to be associated with mental health problems in early adulthood, and socioeconomic outcomes were better among those who experienced abortion compared with those who gave birth. WHAT IS KNOWN ALREADY: Teenage motherhood has been linked with numerous adverse outcomes in later life, including low educational levels and poor physical and mental health. Whether abortion at a young age predisposes to similar consequences is not clear. STUDY DESIGN, SIZE, DURATION: This nationwide, retrospective cohort study from Finland, included all women born in 1987 (n = 29 041) and followed until 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed socioeconomic, psychiatric and risk-taking-related health outcomes up to 25 years of age after underage (<18 years) abortion (n = 1041, 3.6%) and after childbirth (n = 394, 1.4%). Before and after conception analyses within the study groups were performed to further examine the association between abortion and adverse health outcomes. A group with no pregnancies up to 20 years of age (n = 25 312, 88.0%) served as an external reference group. MAIN RESULTS AND THE ROLE OF CHANCE: We found no significant differences between the underage abortion and the childbirth group regarding risks of psychiatric disorders (adjusted odds ratio 0.96 [0.67-1.40]) or suffering from intentional or unintentional poisoning by medications or drugs (1.06 [0.57-1.98]). Compared with those who gave birth, girls who underwent abortion were less likely to achieve only a low educational level (0.41 [95% confidence interval 0.31-0.54]) or to be welfare-dependent (0.31 [0.22-0.45]), but more likely to suffer from injuries (1.51 [1.09-2.10]). Compared with the external control group, both pregnancy groups were disadvantaged already prior to the pregnancy. Psychiatric disorders and risk-taking-related health outcomes, including injury, were increased in the abortion group and in the childbirth group similarly on both sides of the pregnancy. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study remains a limitation. The identification of study subjects in order to collect additional data was not allowed for ethical reasons. Therefore further confounding factors, such as the intentionality of the pregnancy, could not be checked. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies have found that abortion is not harmful to mental health in the majority of adult women. Our study adds to the current understanding in suggesting that this is also the case concerning underage girls. Furthermore, women with a history of underage abortion had better socioeconomic outcomes compared with those who gave birth. These findings can be generalized to settings of high quality social and health-care services, where abortion is accessible and affordable to all citizens. Social and health-care professionals who care for and counsel underage girls facing unplanned pregnancy should acknowledge this information. STUDY FUNDING/COMPETING INTERESTS: This study was financially supported by the Finnish Cultural Foundation and the Paivikki and Sakari Sohlberg Foundation. The researchers are independent of funders and the funders had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors have no competing interests. PMID- 27402910 TI - Fertility-related quality of life from two RCT cohorts with infertility: unexplained infertility and polycystic ovary syndrome. AB - STUDY QUESTION: Does fertility-related quality of life (FertiQOL) differ by infertility diagnosis between women with polycystic ovary syndrome (PCOS) and their partners, compared with couples with unexplained infertility (UI)? SUMMARY ANSWER: Women with PCOS report lower QOL than those with UI, whereas males with UI report lower QOL than males with PCOS partners. WHAT IS KNOWN ALREADY: The fertility-specific QOL survey, FertiQOL, has been used to examine fertility related QOL in a number of worldwide cohorts. Few data have addressed fertility related QOL as a function of infertility diagnosis. Overall, men report better QOL than women with infertility, and there is variation in FertiQOL scores across different samples from different countries. STUDY DESIGN, SIZE, DURATION: This was a prospective, cohort study derived from two concurrent, randomized clinical trials, and designed to examine QOL in infertile females with PCOS and UI at the time of enrollment compared with each other and their male partners; to compare concordance FertiQOL scores in this study across other worldwide cohorts; and to determine if baseline FertiQOL was associated with pregnancy outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS and their partners (n = 733 and n = 641, respectively), and couples with UI (n = 865 women and 849 men) completed a validated fertility-specific QOL survey (FertiQOL) at the time of the study screening visit. PCOS women were randomized to either clomiphene citrate or letrozole treatment; couples with UI were randomized to clomiphene citrate, letrozole or gonadotrophin plus IUI. FertiQOL results were compiled by diagnosis (PCOS or UI) and compared by diagnosis and sex using Wilcoxon Rank-Sum testing. Relationships between baseline FertiQOL and pregnancy outcomes were examined using logistic regression. Multivariable models were performed to assess the association between FertiQOL scores and key participant characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS had lower total FertiQOL scores (72.3 +/- 14.8) than those with UI (77.1 +/- 12.8; P < 0.001); this was true for each domain (except Relational). These differences were largely explained by variation in BMI, hirsutism, household income and age. Women had lower overall FertiQOL scores than their male partners. Males with PCOS partners had higher scores than males with UI (84.9 +/- 10.2 versus 83.3 +/- 10.8; P = 0.003). Scores were not consistently associated with conception or pregnancy outcome. LIMITATIONS, REASONS FOR CAUTION: The use of multiple tests of association may have resulted in spurious statistically significant findings. Inherent sociodemographic differences between women with PCOS and those with UI largely account for the lower QOL in women with PCOS. Our study was unable to assess if changes in QOL affected pregnancy outcome as FertiQOL data were collected prior to treatment. Finally, the participants for both studies represent their local communities, but are not a population-based sample and thus firm conclusions about how representative these couples are to the general population must be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: Women with PCOS with elevated BMI and hirsutism scores and with lower socioeconomic status may require more, targeted psychosocial support than those with other diagnoses. Possible attribution of infertility to the male partner appears to result in a lower QOL. There appears to be substantial national variation in FertiQOL scores, with US based cohorts reporting overall higher QOL. STUDY FUNDING/COMPETING INTERESTS: This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD39005 (to M.D.), U10 HD38992 (to R.S.L.), (to C.C.), U10 HD38998 (to R.A.), U10 HD055942 (to R.D.R.), HD055944 (to P.C.), U10 HD055936 (to G.C.), U10HD055925 (to H.Z.); and U10 U54-HD29834 (to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research). Most importantly, this research was made possible by the funding by American Recovery and Reinvestment Act. N.S., E.E., J.C.T., C.G., H.H., R.A., P.C., G.C., C.C., M.D., S.J., W.D.S. and H.Z. report no conflicts of interests/disclosures. L.B.C. reports research support from Ferring Pharmaceuticals and Roche Diagnostics; R.S.L. reports receipt of consulting fees from AstraZeneca, Euroscreen, Sprout Pharmaceuticals, Taken, Kindex, Clarus and Bayer, Inc., and research support from AstraZeneca and Ferring Pharmaceuticals. R.D.R. reports research support from AbbVie. TRIAL REGISTRATION NUMBER: Pregnancy in Polycystic Ovary Syndrome II (PPCOS II), NCT00719186; Assessment of Multiple Intrauterine Gestations in Ovulation Stimulation (AMIGOS) NCT01044862, clinicaltrials.gov. TRIAL REGISTRATION DATE: PPCOS II 17 July 2008; AMIGOS 7 January 2010. DATE OF FIRST PATIENT'S ENROLMENT: PPCOS II 19 February 2009; AMIGOS 2 August 2010. PMID- 27402911 TI - Advanced maternal age causes adverse programming of mouse blastocysts leading to altered growth and impaired cardiometabolic health in post-natal life. AB - STUDY QUESTION: Does advanced maternal age (AMA) in mice affect cardiometabolic health during post-natal life in offspring derived from an assisted reproduction technology (ART) procedure? SUMMARY ANSWER: Offspring derived from blastocysts collected from aged female mice displayed impaired body weight gain, blood pressure, glucose metabolism and organ allometry during post-natal life compared with offspring derived from blastocysts from young females; since all blastocysts were transferred to normalized young mothers, this effect is independent of maternal pregnancy conditions. WHAT IS KNOWN ALREADY: Although studies in mice have shown that AMA can affect body weight and behaviour of offspring derived from natural reproduction, data on the effects of AMA on offspring cardiometabolic health during post-natal development are not available. Given the increasing use of ART to alleviate infertility in women of AMA, it is pivotal to develop ART-AMA models addressing the effects of maternal aging on offspring health. STUDY DESIGN, SIZE, DURATION: Blastocysts from old (34-39 weeks) or young (8-9 weeks) C57BL/6 females mated with young CBA males (13-15 weeks) were either subjected to differential cell staining (inner cell mass and trophectoderm) or underwent embryo transfer (ET) into young MF1 surrogates (8-9 weeks) to produce young (Young-ET, 9 litters) and old (Old-ET, 10 litters) embryo-derived offspring. Offspring health monitoring was carried out for 30 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: All animals were fed with standard chow. Blood pressure was measured at post-natal Weeks 9, 15 and 21, and at post natal Week 30 a glucose tolerance test (GTT) was performed. Two days after the GTT mice were killed for organ allometry. Blastocyst cell allocation variables were evaluated by T-test and developmental data were analysed with a multilevel random effects regression model. MAIN RESULTS AND THE ROLE OF CHANCE: The total number of cells in blastocysts from aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean +/- SEM: 34.5 +/- 2.1 versus 29.6 +/- 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 +/- 0.8 versus 33.4 +/- 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9 15 in males (Week 9: 108.5 +/- 3.13 versus 100.8 +/- 1.5 mmHg, Week 15: 112.9 +/- 3.2 versus 103.4 +/- 2.1 mmHg) and Week 15 in females (115.9 +/- 3.7 versus 102.8 +/- 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 +/- 0.4 versus 17.8 +/- 1.16 mmol/l) and their spleen weight (88.2 +/- 2.6 +/- 105.1 +/- 4.6 mg) and several organ:body weight ratios (g/g * 10(3)) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 +/- 0.06 versus 4.4 +/- 0.08), lungs (4.4 +/- 0.1 versus 5.0 +/- 0.1), spleen (2.4 +/- 0.06 versus 3.2 +/- 0.1) and liver (36.4 +/- 0.6 versus 39.1 +/- 0.9). LIMITATIONS, REASONS FOR CAUTION: Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans). WIDER IMPLICATIONS OF THE FINDINGS: Our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for women of AMA undergoing assisted reproduction, including surrogacy programmes. STUDY FUNDING/COMPETING INTERESTS: This work was supported through the European Union FP7-CP-FP Epihealth programme (278418) to T.P.F. and the BBSRC (BB/F007450/1) to T.P.F. The authors have no conflicts of interest to declare. PMID- 27402912 TI - Handgrip Strength Index Predicts Nutritional Status as a Complement to Body Mass Index in Crohn's Disease. AB - BACKGROUND: Body mass index [BMI] is widely used to measure nutritional status in Crohn's disease [CD] patients, but limitations remain. Measuring handgrip strength index, in addition to BMI, may aid in overcoming limitations. METHODS: A total of 150 patients with CD and 254 controls were included in this study. All patients and controls underwent BMI, handgrip strength and bioelectrical impedance analysis. Bioelectrical impedance analysis included body cell mass, bone mineral content, skeletal muscle mass and body fat mass. A total of 88 CD patients were age-, sex- and BMI-matched with healthy controls for further analysis. RESULTS: BMI, body cell mass, body cell mass index, handgrip strength and handgrip strength index were all significantly decreased in the group of CD patients compared with controls [p < 0.0001]. When paired by BMI, healthy controls had significantly increased body cell mass index[p = 0.0344] and handgrip strength index [p = 0.0010] compared to patients. In addition, handgrip strength was well correlated with body cell mass [r = 0.8365, p < 0.0001]. CONCLUSIONS: BMI is widely used for detecting malnutrition, but it is less sensitive in predicting loss of body cell mass and skeletal muscle mass. Our study shows that handgrip strength index is an effective and convenient parameter to predict the functional nutritional status and muscular health in CD patients. PMID- 27402914 TI - Is Super-Selective Superior? PMID- 27402913 TI - Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease. AB - BACKGROUND AND AIMS: Only a quarter of thiopurine-induced myelotoxicity in inflammatory bowel disease [IBD] patients is related to thiopurine S methyltransferase deficiency. We determined the predictive value of 6-thioguanine nucleotide [6-TGN] and 6-methylmercaptopurine ribonucleotide [6-MMPR] concentrations 1 week after initiation [T1] for development of leukopenia during the first 8 weeks of thiopurine treatment. METHODS: The study was performed in IBD patients starting thiopurine therapy as part of the Dutch randomized controlled TOPIC trial [ClinicalTrials.gov NCT00521950]. Blood samples for metabolite measurement were collected at T1. Leukopenia was defined by leukocyte counts of <3.0 * 109/L. For comparison, patients without leukopenia who completed the 8 weeks on the stable dose were selected from the first 272 patients of the TOPIC trial. RESULTS: Thirty-two patients with, and 162 patients without leukopenia were analysed. T1 threshold 6-TGN concentrations of 213 pmol/8 * 108 erythrocytes and 3525 pmol/8 * 108 erythrocytes for 6-MMPR were defined: patients exceeding these values were at increased leukopenia risk (odds ratio [OR] 6.2 [95% CI: 2.8-13.8] and 5.9 [95% CI: 2.7-13.3], respectively). Leukopenia rates were higher in patients treated with mercaptopurine, compared with azathioprine (OR 7.3 [95% CI: 3.1-17.0]), and concurrent anti-TNF therapy (OR 5.1 [95% CI: 1.6 16.4]). Logistic regression analysis of thiopurine type, threshold concentrations, and concurrent anti-tumour necrosis factor [TNF] therapy revealed that elevations of both T1 6-TGN and 6-MMPR resulted in the highest risk for leukopenia, followed by exceeding only the T1 6-MMPR or 6-TGN threshold concentration (area under the curve 0.84 [95% CI: 0.76-0.92]). CONCLUSIONS: In ~80% of patients, leukopenia could be explained by T1 6-TGN and/or 6-MMPR elevations. Validation of the predictive model is needed before implementing in clinical practice. PMID- 27402915 TI - Post-Induction Adalimumab Concentration is Associated with Short-Term Mucosal Healing in Patients with Ulcerative Colitis. AB - BACKGROUND AND AIMS: Mucosal healing is associated with favourable therapeutic outcomes in patients with ulcerative colitis [UC]. We investigated whether adalimumab concentrations during induction therapy are associated with short-term mucosal healing [STMH] in UC patients. METHODS: This was a retrospective, single centre study including consecutive UC patients treated with adalimumab from June 2005 to May 2014, who underwent an endoscopy both at baseline and after induction therapy [weeks 8-14] and at least one serum sample available at week 2 and/or week 4. STMH was defined as Mayo endoscopic sub-score of <=1 with a baseline sub score of >=2. Adalimumab concentrations were evaluated using an in-house developed enzyme-linked immunosorbent assay. RESULTS: The study population consisted of 43 patients, the majority of whom [n = 38] were prior infliximab failures; the rest showed primary non-response [PNR, n = 5]. Twelve patients [27.9%] achieved STMH. Patients with STMH had higher adalimumab concentrations at week 4 compared to those without [10.6 vs 7.4 MUg/ml, p = 0.014]. A receiver operating characteristic [ROC] analysis identified an adalimumab concentration threshold at week 4 of 9.4 MUg/ml (area under the ROC curve [AUROC]: 0.778) and 7.5 MUg/ml [AUROC: 0.798], after excluding patients with PNR to infliximab, to be associated with STMH. Multiple logistic regression analysis, after excluding patients with PNR to infliximab, identified adalimumab concentration >=7.5 MUg/ml at week 4 (odds ratio [OR]: 15.7; 95% confidence interval [CI]: 1.3-185; p = 0.029) and baseline endoscopic Mayo score 3 [OR: 0.13; 95% CI: 0.02-0.98; p = 0.047] as factors independently associated with STMH. CONCLUSIONS: This study, reflecting real-life clinical practice, demonstrated that post-induction adalimumab concentrations are associated with STMH, while higher baseline mucosal inflammation is related to lack of STMH in UC. PMID- 27402916 TI - Negative Screening Does Not Rule Out the Risk of Tuberculosis in Patients with Inflammatory Bowel Disease Undergoing Anti-TNF Treatment: A Descriptive Study on the GETAID Cohort. AB - AIM: to describe the characteristics of incident cases of tuberculosis [TB] despite negative TB screening tests, in patients with inflammatory bowel disease [IBD] undergoing anti-TNF treatment, and to identify the risk factors involved. METHODS: A retrospective descriptive study was conducted at GETAID centers on all IBD patients undergoing anti-TNF treatment who developed TB even though their initial screening test results were negative. The following data were collected using a standardized anonymous questionnaire: IBD, and TB characteristics and evolution, initial screening methods and results, and time before anti-TNF treatment was restarted. RESULTS: A total of 44 IBD patients [including 23 men; median age 37 years] were identified at 20 French and Swiss centers at which TB screening was performed [before starting anti-TNF treatment] based on Tuberculin Skin Tests [n = 25], Interferon Gamma Release Assays [n = 12], or both [n = 7]. The median interval from the start of anti-TNF treatment to TB diagnosis was 14.5 months (interquartile range [IQR] 25-75: 4.9-43.3). Pulmonary TB involvement was observed in 25 [57%] patients, and 40 [91%] had at least one extrapulmonary location. One TB patient died as the result of cardiac tamponade. Mycobacterium tuberculosis exposure was thought to be a possible cause of TB in 14 cases [32%]: 7 patients [including 6 health care workers] were exposed to occupational risks, and 7 had travelled to endemic countries. Biotherapy was restarted on 27 patients after a median period of 11.2 months [IQR 25-75: 4.4-15.2] after TB diagnosis without any recurrence of the infection. CONCLUSION: Tuberculosis can occur in IBD patients undergoing anti-TNF treatment, even if their initial screening results were negative. In the present population, TB was mostly extrapulmonary and disseminated. TB screening tests should be repeated on people exposed to occupational risks and/or travelers to endemic countries. Restarting anti-TNF treatment seems to be safe. PMID- 27402917 TI - Invasively Measured Aortic Systolic Blood Pressure and Office Systolic Blood Pressure in Cardiovascular Risk Assessment: A Prospective Cohort Study. AB - Aortic systolic blood pressure (BP) represents the hemodynamic cardiac and cerebral burden more directly than office systolic BP. Whether invasively measured aortic systolic BP confers additional prognostic value beyond office BP remains debated. In this study, office systolic BP and invasively measured aortic systolic BP were recorded in 21 908 patients (mean age: 63 years; 58% men; 14% with diabetes mellitus) with stable angina pectoris undergoing elective coronary angiography during January 2001 to December 2012. Multivariate Cox models were used to assess the association with incident myocardial infarction, stroke, and death. Discrimination and reclassification were assessed using Harrell's C and the Continuous Net Reclassification Index. Data were analyzed with and without stratification by diabetes mellitus status. During a median follow-up period of 3.7 years (range: 0.1-10.8 years), 422 strokes, 511 myocardial infarctions, and 1530 deaths occurred. Both office and aortic systolic BP were associated with stroke in patients with diabetes mellitus (hazard ratio per 10 mm Hg, 1.18 [95% confidence interval, 1.07-1.30] and 1.14 [95% confidence interval, 1.05-1.24], respectively) and with myocardial infarction in patients without diabetes mellitus (hazard ratio, 1.07 [95% confidence interval, 1.02-1.12] and 1.05 [95% confidence interval, 1.01-1.10], respectively). In models including both BP measurements, aortic BP lost statistical significance and aortic BP did not confer improvement in either C-statistics or net reclassification analysis. In conclusion, invasively measured aortic systolic BP does not add prognostic information about cardiovascular outcomes and all-cause mortality compared with office BP in patients with stable angina pectoris, either with or without diabetes mellitus. PMID- 27402918 TI - Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy. AB - RAMPs (receptor activity-modifying proteins) serve as oligomeric modulators for numerous G-protein-coupled receptors, yet elucidating the physiological relevance of these interactions remains complex. Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null for canonical adrenomedullin/calcitonin receptor-like receptor signaling. We aimed to genetically rescue the Ramp2(-/-) lethality in order to further delineate the spatiotemporal requirements for RAMP2 function during development and thereby enable the elucidation of an expanded repertoire of RAMP2 functions with family B G-protein-coupled receptors in adult homeostasis. Endothelial-specific expression of Ramp2 under the VE-cadherin promoter resulted in the partial rescue of Ramp2( /-) mice, demonstrating that endothelial expression of Ramp2 is necessary and sufficient for survival. The surviving Ramp2(-/-) Tg animals lived to adulthood and developed spontaneous hypotension and dilated cardiomyopathy, which was not observed in adult mice lacking calcitonin receptor-like receptor. Yet, the hearts of Ramp2(-/-) Tg animals displayed dysregulation of family B G-protein-coupled receptors, including parathyroid hormone and glucagon receptors, as well as their downstream signaling pathways. These data suggest a functional requirement for RAMP2 in the modulation of additional G-protein-coupled receptor pathways in vivo, which is critical for sustained cardiovascular homeostasis. The cardiovascular importance of RAMP2 extends beyond the endothelium and canonical adrenomedullin/calcitonin receptor-like receptor signaling, in which future studies could elucidate novel and pharmacologically tractable pathways for treating cardiovascular diseases. PMID- 27402920 TI - Atrial Fibrillation in Patients With Hypertension: Trajectories of Risk Factors in Yet Another Manifestation of Hypertensive Target Organ Damage. PMID- 27402919 TI - Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Mediated Redox Signaling and Vascular Remodeling by 16alpha-Hydroxyestrone in Human Pulmonary Artery Cells: Implications in Pulmonary Arterial Hypertension. AB - Estrogen and oxidative stress have been implicated in pulmonary arterial hypertension (PAH). Mechanisms linking these systems are elusive. We hypothesized that estrogen metabolite, 16alpha-hydroxyestrone (16alphaOHE1), stimulates nicotinamide adenine dinucleotide phosphate oxidase (Nox)-induced reactive oxygen species (ROS) generation and proliferative responses in human pulmonary artery smooth muscle cells (hPASMCs) and that in PAH aberrant growth signaling promotes vascular remodeling. The pathophysiological significance of estrogen-Nox dependent processes was studied in female Nox1(-/-) and Nox4(-/-) mice with PAH. PASMCs from control subjects (control hPASMCs) and PAH patients (PAH-hPASMCs) were exposed to estrogen and 16alphaOHE1 in the presence/absence of inhibitors of Nox, cytochrome P450 1B1, and estrogen receptors. Estrogen, through estrogen receptor-alpha, increased Nox-derived ROS and redox-sensitive growth in hPASMCs, with greater effects in PAH-hPASMCs versus control hPASMCs. Estrogen effects were inhibited by cytochrome P450 1B1 blockade. 16alphaOHE1 stimulated transient ROS production in hPASMCs, with sustained responses in PAH-hPASMCs. Basal expression of Nox1/Nox4 was potentiated in PAH-hPASMCs. In hPASMCs, 16alphaOHE1 increased Nox1 expression, stimulated irreversible oxidation of protein tyrosine phosphatases, decreased nuclear factor erythroid-related factor 2 activity and expression of nuclear factor erythroid-related factor 2-regulated antioxidant genes, and promoted proliferation. This was further amplified in PAH-hPASMCs. Nox1(-/-) but not Nox4(-/-) mice were protected against PAH and vascular remodeling. Our findings demonstrate that in PAH-hPASMCs, 16alphaOHE1 stimulates redox-sensitive cell growth primarily through Nox1. Supporting this, in vivo studies exhibited protection against pulmonary hypertension and remodeling in Nox1(-/-) mice. This study provides new insights through Nox1/ROS and nuclear factor erythroid-related factor 2 whereby 16alphaOHE1 influences hPASMC function, which when upregulated may contribute to vascular injury in PAH, particularly important in women. PMID- 27402922 TI - Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. AB - The antihypertensive effect of magnesium (Mg) supplementation remains controversial. We aimed to quantify the effect of oral Mg supplementation on blood pressure (BP) by synthesizing available evidence from randomized, double blind, placebo-controlled trials. We searched trials of Mg supplementation on normotensive and hypertensive adults published up to February 1, 2016 from MEDLINE and EMBASE databases; 34 trials involving 2028 participants were eligible for this meta-analysis. Weighted mean differences of changes in BP and serum Mg were calculated by random-effects meta-analysis. Mg supplementation at a median dose of 368 mg/d for a median duration of 3 months significantly reduced systolic BP by 2.00 mm Hg (95% confidence interval, 0.43-3.58) and diastolic BP by 1.78 mm Hg (95% confidence interval, 0.73-2.82); these reductions were accompanied by 0.05 mmol/L (95% confidence interval, 0.03, 0.07) elevation of serum Mg compared with placebo. Using a restricted cubic spline curve, we found that Mg supplementation with a dose of 300 mg/d or duration of 1 month is sufficient to elevate serum Mg and reduce BP; and serum Mg was negatively associated with diastolic BP but not systolic BP (all P<0.05). In the stratified analyses, a greater reduction in BP tended to be found in trials with high quality or low dropout rate (all P values for interaction <0.05). However, residual heterogeneity may still exist after considering these possible factors. Our findings indicate a causal effect of Mg supplementation on lowering BPs in adults. Further well-designed trials are warranted to validate the BP-lowering efficacy of optimal Mg treatment. PMID- 27402923 TI - (Magneto)caloric refrigeration: is there light at the end of the tunnel? AB - Caloric cooling and heat pumping rely on reversible thermal effects triggered in solids by magnetic, electric or stress fields. In the recent past, there have been several successful demonstrations of using first-order phase transition materials in laboratory cooling devices based on both the giant magnetocaloric and elastocaloric effects. All such materials exhibit non-equilibrium behaviours when driven through phase transformations by corresponding fields. Common wisdom is that non-equilibrium states should be avoided; yet, as we show using a model material exhibiting a giant magnetocaloric effect, non-equilibrium phase separated states offer a unique opportunity to achieve uncommonly large caloric effects by very small perturbations of the driving field(s).This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402921 TI - Impact of Cardiovascular Risk Factors on Graft Outcome Disparities in Black Kidney Transplant Recipients. AB - Although outcome inequalities for non-Hispanic black (NHB) kidney transplant recipients are well documented, there is paucity in data assessing the impact of cardiovascular disease (CVD) risk factors on this disparity in kidney transplantation. This was a longitudinal study of a national cohort of veteran kidney recipients transplanted between January 2001 and December 2007. Data included baseline characteristics acquired through the United States Renal Data System linked to detailed clinical follow-up information acquired through the Veterans Affairs electronic health records. Analyses were conducted using sequential multivariable modeling (Cox regression), incorporating blocks of variables into iterative nested models; 3139 patients were included (2095 non Hispanic whites [66.7%] and 1044 NHBs [33.3%]). NHBs had a higher prevalence of hypertension (100% versus 99%; P<0.01) and post-transplant diabetes mellitus (59% versus 53%; P<0.01) with reduced control of hypertension (blood pressure <140/90 60% versus 69%; P<0.01), diabetes mellitus (A1c <7%, 35% versus 47%; P<0.01), and low-density lipoprotein (<100 mg/dL, 55% versus 61%; P<0.01). Adherence to medications used to manage CVD risk was significantly lower in NHBs. In the fully adjusted models, the independent risk of graft loss in NHBs was substantially reduced (unadjusted hazard ratio, 2.00 versus adjusted hazard ratio, 1.49). CVD risk factors and control reduced the influence of NHB race by 9% to 18%. Similar trends were noted for mortality, and estimates were robust across in sensitivity analyses. These results demonstrate that NHB kidney transplant recipients have significantly higher rates of CVD risk factors and reduced CVD risk control. These issues are likely partly related to medication nonadherence and meaningfully contribute to racial disparities for graft outcomes. PMID- 27402924 TI - A universal metric for ferroic energy materials. AB - After almost 20 years of intensive research on magnetocaloric effects near room temperature, magnetic refrigeration with first-order magnetocaloric materials has come close to real-life applications. Many materials have been discussed as potential candidates to be used in multicaloric devices. However, phase transitions in ferroic materials are often hysteretic and a metric is needed to estimate the detrimental effects of this hysteresis. We propose the coefficient of refrigerant performance, which compares the net work in a reversible cycle with the positive work on the refrigerant, as a universal metric for ferroic materials. Here, we concentrate on examples from magnetocaloric materials and only consider one barocaloric experiment. This is mainly due to lack of data on electrocaloric materials. It appears that adjusting the field-induced transitions and the hysteresis effects can minimize the losses in first-order materials.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402926 TI - Taking the temperature of phase transitions in cool materials. PMID- 27402925 TI - Thermodynamics of multicaloric effects in multiferroic materials: application to metamagnetic shape-memory alloys and ferrotoroidics. AB - We develop a general thermodynamic framework to investigate multicaloric effects in multiferroic materials. This is applied to the study of both magnetostructural and magnetoelectric multiferroics. Landau models with appropriate interplay between the corresponding ferroic properties (order parameters) are proposed for metamagnetic shape-memory and ferrotoroidic materials, which, respectively, belong to the two classes of multiferroics. For each ferroic property, caloric effects are quantified by the isothermal entropy change induced by the application of the corresponding thermodynamically conjugated field. The multicaloric effect is obtained as a function of the two relevant applied fields in each class of multiferroics. It is further shown that multicaloric effects comprise the corresponding contributions from caloric effects associated with each ferroic property and the cross-contribution arising from the interplay between these ferroic properties.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402927 TI - Electrocaloric and elastocaloric effects in soft materials. AB - Materials with large caloric effect have the promise of realizing solid-state refrigeration which has potential to be more efficient and environmentally friendly compared with current cooling technologies. Recently, the focus of caloric effects investigations has shifted towards soft materials. An overview of recent direct measurements of the large electrocaloric effect (ECE) in a composite mixture of a liquid crystal and nanoparticles (NPs) and large elastocaloric (eC) effect in main-chain liquid crystal elastomers is given. In mixtures of 12CB liquid crystal with functionalized CdSSe NPs, an ECE exceeding 5 K was found in the vicinity of the isotropic to smectic A phase transition. It is shown that the NPs smear the isotropic to smectic coexistence range in which a large ECE is observed due to latent heat enhancement. NPs acting as traps for ions reduce the moving-ion density and consequently the Joule heating. Direct eC measurements indicate that the significant eC response can be found in main-chain liquid crystalline elastomers, but at a fraction of the stress field in contrast to other eC materials. Both soft materials could play a significant role as active cooling elements or parts of thermal diodes in development of new cooling devices.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402928 TI - Mastering hysteresis in magnetocaloric materials. AB - Hysteresis is more than just an interesting oddity that occurs in materials with a first-order transition. It is a real obstacle on the path from existing laboratory-scale prototypes of magnetic refrigerators towards commercialization of this potentially disruptive cooling technology. Indeed, the reversibility of the magnetocaloric effect, being essential for magnetic heat pumps, strongly depends on the width of the thermal hysteresis and, therefore, it is necessary to understand the mechanisms causing hysteresis and to find solutions to minimize losses associated with thermal hysteresis in order to maximize the efficiency of magnetic cooling devices. In this work, we discuss the fundamental aspects that can contribute to thermal hysteresis and the strategies that we are developing to at least partially overcome the hysteresis problem in some selected classes of magnetocaloric materials with large application potential. In doing so, we refer to the most relevant classes of magnetic refrigerants La-Fe-Si-, Heusler- and Fe2P-type compounds.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402929 TI - Magnetic relaxation dynamics driven by the first-order character of magnetocaloric La(Fe,Mn,Si)13. AB - Here, we study the temporal evolution of the magnetic field-driven paramagnetic to ferromagnetic transition in the La(Fe,Mn,Si)13 material family. Three compositions are chosen that show varying strengths of the first-order character of the transition, as determined by the relative magnitude of their magnetic hysteresis and temperature separation between the zero-field transition temperature Tc and the temperature Tcrit, where the transition becomes continuous. Systematic variations in the fixed field, isothermal rate of relaxation are observed as a function of temperature and as a function of the degree of first-order character. The relaxation rate is reduced in more weakly first-order compositions and is also reduced as the temperature is increased towards Tcrit At temperatures above Tcrit, the metastability of the transition vanishes along with its associated temporal dynamics.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402930 TI - Large electrocaloric effects in single-crystal ammonium sulfate. AB - Electrocaloric (EC) effects are typically studied near phase transitions in ceramic and polymer materials. Here, we investigate EC effects in an inorganic salt, namely ammonium sulfate (NH4)2SO4, with an order-disorder transition whose onset occurs at 223 K on cooling. For a single crystal thinned to 50 MUm, we use a Maxwell relation to find a large isothermal entropy change of 30 J K(-1) kg(-1) in response to a field change of 400 kV cm(-1) The Clausius-Clapeyron equation implies a corresponding adiabatic temperature change of 4.5 K.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402931 TI - Mechanocaloric effects in shape memory alloys. AB - Shape memory alloys (SMA) are a class of ferroic materials which undergo a structural (martensitic) transition where the associated ferroic property is a lattice distortion (strain). The sensitiveness of the transition to the conjugated external field (stress), together with the latent heat of the transition, gives rise to giant mechanocaloric effects. In non-magnetic SMA, the lattice distortion is mostly described by a pure shear and the martensitic transition in this family of alloys is strongly affected by uniaxial stress, whereas it is basically insensitive to hydrostatic pressure. As a result, non magnetic alloys exhibit giant elastocaloric effects but negligible barocaloric effects. By contrast, in a number of magnetic SMA, the lattice distortion at the martensitic transition involves a volume change in addition to the shear strain. Those alloys are affected by both uniaxial stress and hydrostatic pressure and they exhibit giant elastocaloric and barocaloric effects. The paper aims at providing a critical survey of available experimental data on elastocaloric and barocaloric effects in magnetic and non-magnetic SMA.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402932 TI - Large elastic strain and elastocaloric effect caused by lattice softening in an iron-palladium alloy. AB - A Fe-31.2Pd (at.%) alloy exhibits a weak first-order martensitic transformation from a cubic structure to a tetragonal structure near 230 K. This transformation is associated with significant softening of elastic constant C'. Because of the softening, the alloy shows a large elastic strain of more than 6% in the [001] direction. In addition, the alloy has a critical point and shows a high elastocaloric effect in a wide temperature range for both the parent and the martensite phases.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402933 TI - Fatigue effect of elastocaloric properties in natural rubber. AB - In the framework of elastocaloric (eC) refrigeration, the fatigue effect on the eC effect of natural rubber (NR) is investigated. Repetitive deformation cycles at engineering strain regime from 1 to 6 results in a rapid rupture (approx. 800 cycles). Degradation of properties and fatigue life are then investigated at three different strain regimes with the same strain amplitude: before onset strain of strain-induced crystallization (SIC) (strain regime of 0-3), onset strain of melting (strain regime of 2-5) and high strain of SIC (strain regime of 4-7). Strain of 0-3 leads to a low eC effect and cracking after 2000 cycles. Strain of 2-5 and 4-7 results in an excellent crack growth resistance and much higher eC effect with adiabatic temperature changes of 3.5 K and 4.2 K, respectively, thanks to the effect of SIC. The eC stress coefficient index gamma (ratio between eC temperature change and applied stress) for strains of 2-5 and 4 7 are gamma2-5=4.4 K MPa(-1) and gamma4-7=1.6 K MPa(-1), respectively, demonstrating the advantage of the strain regime 2-5. Finally, a high-cycle test up to 1.7*10(5) cycles is successfully applied to the NR sample with very little degradation of eC properties, constituting an important step towards cooling applications.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402934 TI - Influence of the transition width on the magnetocaloric effect across the magnetostructural transition of Heusler alloys. AB - We report a complete structural and magneto-thermodynamic characterization of four samples of the Heusler alloy Ni-Co-Mn-Ga-In, characterized by similar compositions, critical temperatures and high inverse magnetocaloric effect across their metamagnetic transformation, but different transition widths. The object of this study is precisely the sharpness of the martensitic transformation, which plays a key role in the effective use of materials and which has its origin in both intrinsic and extrinsic effects. The influence of the transition width on the magnetocaloric properties has been evaluated by exploiting a phenomenological model of the transformation built through geometrical considerations on the entropy versus temperature curves. A clear result is that a large temperature span of the transformation is unfavourable to the magnetocaloric performance of a material, reducing both isothermal entropy change and adiabatic temperature change obtainable in a given magnetic field and increasing the value of the maximum field needed to fully induce the transformation. The model, which is based on standard magnetometric and conventional calorimetric measurements, turns out to be a convenient tool for the determination of the optimum values of transformation temperature span in a trade-off between sheer performance and amplitude of the operating range of a material.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402935 TI - Effect of crystallographic compatibility and grain size on the functional fatigue of sputtered TiNiCuCo thin films. AB - The positive influence of crystallographic compatibility on the thermal transformation stability has been already investigated extensively in the literature. However, its influence on the stability of the shape memory effect or superelasticity used in actual applications is still unresolved. In this investigation sputtered films of a highly compatible TiNiCuCo composition with a transformation matrix middle eigenvalue of 1+/-0.01 are exposed to thermal as well as to superelastic cycling. In agreement with previous results the thermal transformation of this alloy is with a temperature shift of less than 0.1 K for 40 cycles very stable; on the other hand, superelastic degradation behaviour was found to depend strongly on heat treatment parameters. To reveal the transformation dissimilarities between the differently heat-treated samples, the microstructure has been analysed by transmission electron microscopy, in situ stress polarization microscopy and synchrotron analysis. It is found that good crystallographic stability is not a sufficient criterion to avoid defect generation which guarantees high superelastic stability. For the investigated alloy, a small grain size was identified as the determining factor which increases the yield strength of the composition and decreases the functional degradation during superelastic cycling.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402936 TI - Elastocaloric effect in CuAlZn and CuAlMn shape memory alloys under compression. AB - This paper reports the elastocaloric effect of two Cu-based shape memory alloys: Cu68Al16Zn16 (CuAlZn) and Cu73Al15Mn12 (CuAlMn), under compression at ambient temperature. The compression tests were conducted at two different rates to approach isothermal and adiabatic conditions. Upon unloading at a strain rate of 0.1 s(-1) (adiabatic condition) from 4% strain, the highest adiabatic temperature changes (DeltaTad) of 4.0 K for CuAlZn and 3.9 K for CuAlMn were obtained. The maximum stress and hysteresis at each strain were compared. The stress at the maximum recoverable strain of 4.0% for CuAlMn was 120 MPa, which is 70% smaller than that of CuAlZn. A smaller hysteresis for the CuAlMn alloy was also obtained, about 70% less compared with the CuAlZn alloy. The latent heat, determined by differential scanning calorimetry, was 4.3 J g(-1) for the CuAlZn alloy and 5.0 J g(-1) for the CuAlMn alloy. Potential coefficients of performance (COPmat) for these two alloys were calculated based on their physical properties of measured latent heat and hysteresis, and a COPmat of approximately 13.3 for CuAlMn was obtained.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402937 TI - Thickness-dependent electrocaloric effect in mixed-phase Pb0.87Ba0.1 La0.02(Zr0.6Sn0.33Ti0.07)O3 thin films. AB - Full-perovskite Pb0.87Ba0.1La0.02(Zr0.6Sn0.33Ti0.07)O3 (PBLZST) thin films were fabricated by a sol-gel method. These revealed both rhombohedral and tetragonal phases, as opposed to the full-tetragonal phase previously reported in ceramics. The fractions of tetragonal and rhombohedral phases are found to be strongly dependent on film thickness. The fraction of tetragonal grains increases with increasing film thickness, as the substrate constraint throughout the film decreases with film thickness. The maximum of the dielectric constant (epsilonm) and the corresponding temperature (Tm) are thickness-dependent and dictated by the fraction of rhombohedral and tetragonal phase, with epsilonm reaching a minimum at 400 nm and Tm shifting to higher temperature with increasing thickness. With the thickness increase, the breakdown field decreases, but field induced antiferroelectric-ferroelectric (EAFE-FE) and ferroelectric antiferroelectric (EFE-AFE) switch fields increase. The electrocaloric effect increases with increasing film thickness.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402938 TI - Electrocaloric response near room temperature in Zr- and Sn-doped BaTiO3 systems. AB - The electrocaloric effect (ECE) in (1-x)BaZr0.18 Ti0.82O3-(x)BaSn0.11Ti0.89O3 (BZT18-BST11, 0.1<=x<=0.5) ceramics is investigated near room temperature using a calorimetry method. The ceramics exhibit relaxor-like ferroelectric characteristics and by merging phases, a large electrocaloric (EC) response is observed in the system. The largest entropy change is 4.8 Jkg(-1) K(-1) (along with a temperature change of 3.5 K), which is induced under an electric field of 10 MV m(-1) for the 0.8 BaZr0.18Ti0.82O3-0.2 BaSn0.11Ti0.89O3 ceramics. This result reveals that the coexistence of multiple phases improves the ECE of the ceramics, which provides an effective route to achieve a large EC response using a small electric field.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'. PMID- 27402939 TI - MR neurography of a vagal neuropathy. PMID- 27402940 TI - Rupture of vertebral artery dissection aneurysm during 3D DSA. PMID- 27402941 TI - Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta analysis. PMID- 27402942 TI - Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. PMID- 27402943 TI - NDUFA-1 is not a nuclear modifier gene in Leber hereditary optic neuropathy. PMID- 27402945 TI - Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease. PMID- 27402944 TI - Risedronate therapy for prevention of hip fracture after stroke in elderly women; Risedronate therapy for prevention of hip fracture after stroke in elderly women. Reply from the Authors. PMID- 27402946 TI - Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in stroke patients. PMID- 27402947 TI - Clinical Reasoning: A tale of a hypotonic infant. PMID- 27402948 TI - Teaching NeuroImages: Eagle syndrome: Cerebrovascular complications. PMID- 27402949 TI - Teaching NeuroImages: Medullary lesions causing dysphagia in Leigh/MELAS overlap syndrome. PMID- 27402950 TI - Awareness of occupational skin disease in the service sector. AB - Background: Occupational skin disease (OSD) is a common occupational disease. Although primary prevention strategies are known, OSDs remain prevalent in a variety of work environments including the service sector (restaurant/food services, retail/wholesale, tourism/hospitality and vehicle sales and service). Aims: To obtain information about awareness and prevention of OSD in the service sector. Methods: Focus groups and a survey were conducted with two groups. The first consisted of staff of the provincial health and safety association for the service sector and the second group comprised representatives from sector employers. Focus groups highlighted key issues to inform the survey that obtained information about perceptions of awareness and prevention of OSD and barriers to awareness and prevention. Results: Both provincial health and safety association staff and sector employer representatives highlighted low awareness and a low level of knowledge of OSD in the sector. Barriers to awareness and prevention included a low reported incidence of OSD, low priority, lack of training materials, lack of time and cost of training, lack of management support and workplace culture. Conclusions: A starting point for improving prevention of OSD in the service sector is increased awareness. Identification of the barriers to awareness and prevention will help to shape an awareness campaign and prevention strategies. Building on existing experience in Europe will be important. PMID- 27402951 TI - Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling. AB - Inheritance depends on the expansion of a small number of primordial germ cells (PGCs) in the early embryo. Proliferation of mammalian PGCs is concurrent with their movement through changing microenvironments; however, mechanisms coordinating these conflicting processes remain unclear. Here, we find that PGC proliferation varies by location rather than embryonic age. Ror2 and Wnt5a mutants with mislocalized PGCs corroborate the microenvironmental regulation of the cell cycle, except in the hindgut, where Wnt5a is highly expressed. Molecular and genetic evidence suggests that Wnt5a acts via Ror2 to suppress beta-catenin dependent Wnt signaling in PGCs and limit their proliferation in specific locations, which we validate by overactivating beta-catenin in PGCs. Our results suggest that the balance between expansion and movement of migratory PGCs is fine tuned in different niches by the opposing beta-catenin-dependent and Ror2 mediated pathways through Wnt5a This could serve as a selective mechanism to favor early and efficient migrators with clonal dominance in the ensuing germ cell pool while penalizing stragglers. PMID- 27402952 TI - Cortactin promotes exosome secretion by controlling branched actin dynamics. AB - Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in cancer cells leads to a respective decrease or increase in exosome secretion, without altering exosome cargo content. Live-cell imaging revealed that cortactin controls both trafficking and plasma membrane docking of multivesicular late endosomes (MVEs). Regulation of exosome secretion by cortactin requires binding to the branched actin nucleating Arp2/3 complex and to actin filaments. Furthermore, cortactin, Rab27a, and coronin 1b coordinately control stability of cortical actin MVE docking sites and exosome secretion. Functionally, the addition of purified exosomes to cortactin-knockdown cells rescued defects of those cells in serum-independent growth and invasion. These data suggest a model in which cortactin promotes exosome secretion by stabilizing cortical actin-rich MVE docking sites. PMID- 27402953 TI - Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling. AB - Corticotropin-releasing hormone receptor 1 (CRHR1) activates G protein-dependent and internalization-dependent signaling mechanisms. Here, we report that the cyclic AMP (cAMP) response of CRHR1 in physiologically relevant scenarios engages separate cAMP sources, involving the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). cAMP produced by tmACs and sAC is required for the acute phase of extracellular signal regulated kinase 1/2 activation triggered by CRH-stimulated CRHR1, but only sAC activity is essential for the sustained internalization-dependent phase. Thus, different cAMP sources are involved in different signaling mechanisms. Examination of the cAMP response revealed that CRH-activated CRHR1 generates cAMP after endocytosis. Characterizing CRHR1 signaling uncovered a specific link between CRH-activated CRHR1, sAC, and endosome-based signaling. We provide evidence of sAC being involved in an endocytosis-dependent cAMP response, strengthening the emerging model of GPCR signaling in which the cAMP response does not occur exclusively at the plasma membrane and introducing the notion of sAC as an alternative source of cAMP. PMID- 27402955 TI - Spatial resolution of cAMP signaling by soluble adenylyl cyclase. AB - G protein-coupled receptor signaling starts at the plasma membrane and continues at endosomal stations. In this issue, Inda et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201512075) show that different forms of adenylyl cyclase are activated at the plasma membrane versus endosomes, providing a rationale for the spatial encoding of cAMP signaling. PMID- 27402954 TI - Mitotic noncoding RNA processing promotes kinetochore and spindle assembly in Xenopus. AB - Transcription at the centromere of chromosomes plays an important role in kinetochore assembly in many eukaryotes, and noncoding RNAs contribute to activation of the mitotic kinase Aurora B. However, little is known about how mitotic RNA processing contributes to spindle assembly. We found that inhibition of transcription initiation or RNA splicing, but not translation, leads to spindle defects in Xenopus egg extracts. Spliceosome inhibition resulted in the accumulation of high molecular weight centromeric transcripts, concomitant with decreased recruitment of the centromere and kinetochore proteins CENP-A, CENP-C, and NDC80 to mitotic chromosomes. In addition, blocking transcript synthesis or processing during mitosis caused accumulation of MCAK, a microtubule depolymerase, on the spindle, indicating misregulation of Aurora B. These findings suggest that co-transcriptional recruitment of the RNA processing machinery to nascent mitotic transcripts is an important step in kinetochore and spindle assembly and challenge the idea that RNA processing is globally repressed during mitosis. PMID- 27402956 TI - Different expression patterns of LGALS1 and LGALS3 in polycythemia vera, essential thrombocythemia and primary myelofibrosis. AB - Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present study LGALS1 and LGALS3 were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. Increased LGALS3 expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels of LGALS3. Additionally, high LGALS1 expression was found in CD34(+) cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation. PMID- 27402957 TI - Sham Surgery in Orthopedics: A Systematic Review of the Literature. AB - Objective: To evaluate the evidence for the effectiveness of sham surgery in orthopedics by conducting a systematic review of literature. Methods: Systematic searches were conducted on Biomed Central, BMJ.com, CINAHL, the Cochrane Library, NLM Central Gateway, OVID, ProQuest (Digital Dissertations), PsycInfo, PubMed/Medline, ScienceDirect and Web of Science. Secondary searching (PEARLing) was undertaken, whereby reference lists of the selected articles were reviewed for additional references not identified in the primary search. All randomized controlled trials comparing surgery versus sham surgery in orthopedics were included. Data were extracted and methodological quality was assessed by two reviewers using the Critical Review Form-Quantitative Studies. Levels of scientific evidence, based on the direction of outcomes of the trials, were established following the Australian National Health and Medical Research Council (NHMRC) Hierarchy of Evidence (Australian National Health and Medical Research Council, 1999). Results: This review includes six randomized controlled trials (RCTs) involving 277 subjects. All six studies were rated as very good on methodological quality. Heterogeneity across the studies, with respect to participants, interventions evaluated, and outcome measures used, prevented meta analyses. Narrative synthesis of results, based on effect size, demonstrated that sham surgery in orthopedics was as effective as actual surgery in reducing pain and improving disability. Conclusions: This review suggests that sham surgery has shown to be just as effective as actual surgery in reducing pain and disability; however, care should be taken to generalize findings because of the limited number of studies. PMID- 27402959 TI - Is Instant Pain Relief Just a Click Away? PMID- 27402960 TI - Perioperative Pain Management Strategies for Amputation: A Topical Review. AB - Objective: To review acute pain management strategies in patients undergoing amputation with consideration of preoperative patient factors, pharmacologic/interventional modalities, and multidisciplinary care models to alleviate suffering in the immediate post-amputation setting. Background: Regardless of surgical indication, patients undergoing amputation suffer from significant residual limb pain and phantom limb pain in the acute postoperative phase. Most studies have primarily focused on strategies to prevent persistent pain with inclusion of immediate postoperative outcomes as secondary measures. Pharmacologic agents, including gabapentin, ketamine, and calcitonin, and interventional modalities such as neuraxial and perineural catheters, have been examined in the perioperative period. Design: Focused Literature Review. Results: Pharmacologic agents (gabapentin, ketamine, calcitonin) have not shown consistent efficacy. Neuraxial analgesia has demonstrated both an opioid sparing and analgesic benefit while results have been mixed regarding perineural catheters in the immediate post-amputation setting. However, several early studies of perineural catheters employed sub-optimal techniques (distal surgical placement), and prolonged use of perineural catheters may provide a sustained benefit. Regardless of analgesic technique, a multidisciplinary approach is necessary for optimal care. Conclusion: Patient-tailored analgesic regimens utilizing catheter based techniques are essential in the acute post-amputation phase and should be implemented in all patients undergoing amputation. Future research should focus on improved measurement of acute pain and comparisons of effective analgesic regimens instead of single techniques. PMID- 27402961 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27402962 TI - Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination. AB - Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of E cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1(+) epithelium displayed extensive intercellular junctions, and Twist1(-) luminal epithelial cells could still adhere to disseminating Twist1(+) cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1(+) cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate. PMID- 27402963 TI - Modulation of digestive physiology and biochemistry in Mytilus californianus in response to feeding level acclimation and microhabitat. AB - The intertidal mussel Mytilus californianus is a critical foundation species that is exposed to fluctuations in the environment along tidal- and wave-exposure gradients. We investigated feeding and digestion in mussels under laboratory conditions and across environmental gradients in the field. We assessed whether mussels adopt a rate-maximization (higher ingestion and lower assimilation) or a yield-maximization acquisition (lower ingestion and higher assimilation) strategy under laboratory conditions by measuring feeding physiology and digestive enzyme activities. We used digestive enzyme activity to define resource acquisition strategies in laboratory studies, then measured digestive enzyme activities in three microhabitats at the extreme ends of the tidal- and wave-exposure gradients within a stretch of shore (<20 m) projected sea-ward. Our laboratory results indicated that mussels benefit from a high assimilation efficiency when food concentration is low and have a low assimilation efficiency when food concentration is high. Additionally, enzyme activities of carbohydrases amylase, laminarinase and cellulase were elevated when food concentration was high. The protease trypsin, however, did not increase with increasing food concentration. In field conditions, low-shore mussels surprisingly did not have high enzyme activities. Rather, high-shore mussels exhibited higher cellulase activities than low-shore mussels. Similarly, trypsin activity in the high-shore-wave-sheltered microhabitat was higher than that in high-shore-wave-exposed. As expected, mussels experienced increasing thermal stress as a function of reduced submergence from low to high shore and shelter from wave-splash. Our findings suggest that mussels compensate for limited feeding opportunities and thermal stress by modulating digestive enzyme activities. PMID- 27402964 TI - Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation. AB - Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by beta1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and alpha-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca(2+) dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and alpha-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton. PMID- 27402965 TI - Development of a diet-induced murine model of diabetes featuring cardinal metabolic and pathophysiological abnormalities of type 2 diabetes. AB - The persistent rise in global incidence of type 2 diabetes (T2D) continues to have significant public health and economic implications. The availability of relevant animal models of T2D is critical to elucidating the complexity of the pathogenic mechanisms underlying this disease and the implications this has on susceptibility to T2D complications. Whilst many high-fat diet-induced rodent models of obesity and diabetes exist, growing appreciation of the contribution of high glycaemic index diets on the development of hyperglycaemia and insulin resistance highlight the requirement for animal models that more closely represent global dietary patterns reflective of modern society. To that end, we sought to develop and validate a murine model of T2D based on consumption of an energy-dense diet containing moderate levels of fat and a high glycaemic index to better reflect the aetiopathogenesis of T2D. Male C57BL/6 mice were fed an energy dense (ED) diet and the development of pathological features used in the clinical diagnosis of T2D was assessed over a 30-week period. Compared with control mice, 87% of mice fed an ED diet developed pathognomonic signs of T2D including glucose intolerance, hyperglycaemia, glycosylated haemoglobin (HbA1c) and glycosuria within 30 weeks. Furthermore, dyslipidaemia, chronic inflammation, alterations in circulating leucocytes and renal impairment were also evident in ED diet-fed mice compared with mice receiving standard rodent chow. Longitudinal profiling of metabolic and biochemical parameters provide support of an aetiologically and clinically relevant model of T2D that will serve as a valuable tool for mechanistic and therapeutic studies investigating the pathogenic complications of T2D. PMID- 27402966 TI - Hypersalinity drives physiological and morphological changes in Limia perugiae (Poeciliidae). AB - A fundamental question in biology is how an organism's morphology and physiology are shaped by its environment. Here, we evaluate the effects of a hypersaline environment on the morphology and physiology of a population of livebearing fish in the genus Limia (Poeciliidae). We sampled from two populations of Limia perugiae (one freshwater and one hypersaline) in the southwest Dominican Republic. We evaluated relative abundance of osmoregulatory proteins using western blot analyses and used a geometric morphometric approach to evaluate fine scale changes to size and shape. Our data show that gill tissue isolated from hypersaline fish contained approximately two and a half times higher expression of Na(+)/K(+) ATPase proteins. We also show evidence for mitochondrial changes within the gills, with eight times more complex I and four times higher expression of ATP synthase within the gill tissue from the hypersaline population. The energetic consequences to Limia living in saline and hypersaline environments may be a driver for phenotypic diversity, reducing the overall body size and changing the relative size and shape of the head, as well as impeding the growth of secondary sex features among the males. PMID- 27402967 TI - B-type nuclear lamin and the nuclear pore complex Nup107-160 influences maintenance of the spindle envelope required for cytokinesis in Drosophila male meiosis. AB - In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107 depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis. PMID- 27402968 TI - The miR396b of Poncirus trifoliata Functions in Cold Tolerance by Regulating ACC Oxidase Gene Expression and Modulating Ethylene-Polyamine Homeostasis. AB - MicroRNAs (miRNAs) are non-coding regulatory molecules that play important roles in a variety of biological processes. Although a number of cold-responsive miRNAs have been computationally identified, functions and mechanisms of most miRNAs are not well understood. Herein, the function of trifoliate orange [Poncirus trifoliata (L.) Raf.] miRNA396b (ptr-miR396b) in cold tolerance and its potential regulatory module were investigated. Compared with the wild type (WT), transgenic lemon (Citrus limon) plants overexpressing ptr-MIR396b, the precursor of ptr miR396b, displayed enhanced cold tolerance. Ptr-miR396b was experimentally confirmed to guide the cleavage of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO). The overexpressing lines exhibited a reduction in ACO transcript levels and ethylene content compared with the WT, and the expression pattern of ACO was opposite to that of ptr-miR396b in response to cold stress. In addition, the transgenic lines exhibited higher levels of free polyamines and mRNA abundance of polyamine biosynthetic genes than WT plants under cold treatment, consistent with reduced reactive oxygen species (ROS) accumulation in the former. Taken together, this study demonstrates that ptr-miR396b positively regulates cold tolerance through reducing ACO transcript levels, thereby repressing ethylene synthesis and simultaneously promoting polyamine synthesis, leading to enhanced ROS scavenging. Identification of the ptr-miR396b-ACO regulatory module provides new insights into the molecular mechanism underlying the reduction of ethylene production under cold. PMID- 27402969 TI - Cost effectiveness of amoxicillin for lower respiratory tract infections in primary care: an economic evaluation accounting for the cost of antimicrobial resistance. AB - BACKGROUND: Lower respiratory tract infections (LRTIs) are a major disease burden and are often treated with antibiotics. Typically, studies evaluating the use of antibiotics focus on immediate costs of care, and do not account for the wider implications of antimicrobial resistance. AIM: This study sought to establish whether antibiotics (principally amoxicillin) are cost effective in patients with LRTIs, and to explore the implications of taking into account costs associated with resistance. DESIGN AND SETTING: Multinational randomised double-blinded trial in 2060 patients with acute cough/LRTIs recruited in 12 European countries. METHOD: A cost-utility analysis from a health system perspective with a time horizon of 28 days was conducted. The primary outcome measure was the quality adjusted life year (QALY). Hierarchical modelling was used to estimate incremental cost-effectiveness ratios (ICERs). RESULTS: Amoxicillin was associated with an ICER of ?8216 (L6540) per QALY gained when the cost of resistance was excluded. If the cost of resistance is greater than ?11 (L9) per patient, then amoxicillin treatment is no longer cost effective. Including possible estimates of the cost of resistance resulted in ICERs ranging from ?14 730 (L11 949) per QALY gained - when only multidrug resistance costs and health care costs are included - to ?727 135 (L589 856) per QALY gained when broader societal costs are also included. CONCLUSION: Economic evaluation of antibiotic prescribing strategies that do not include the cost of resistance may provide misleading results that could be of questionable use to policymakers. However, further work is required to estimate robust costs of resistance. PMID- 27402970 TI - Variant lattice corneal dystrophy associated with compound heterozygous mutations in the TGFBI gene. AB - BACKGROUND/AIMS: To report the clinical, histopathological and genetic features of a variant of lattice corneal dystrophy (LCD) associated with two pathogenic mutations in the transforming growth factor-B-induced (TGFBI) gene. METHODS: Clinical characterisation was performed by slit lamp examination and in vivo confocal microscopic imaging (IVCM). Histopathological characterisation was performed with light microscopic examination of an excised corneal button and a peripheral blood samples were collected for TGFBI screening. RESULTS: A 42-year old woman presented with progressive photophobia and decreased visual acuity in both eyes. Slit lamp examination demonstrated punctate and linear branching opacities in the mid and posterior corneal stroma, corresponding to hyper reflective opacities noted on IVCM and amyloid deposition noted on histopathological examination of an excised corneal button. TGFBI screening revealed two previously reported heterozygous missense mutations: c.337G>A (p.(Val113Ile)) in exon 4 and c.1673T>C (p.(Leu558Pro)) in exon 12. Screening of an affected sibling with a similar phenotype revealed that she was also heterozygous for both mutations, while screening of another sibling with punctate but not linear stromal opacities revealed that she was heterozygous for only the p.(Leu558Pro) mutation. CONCLUSIONS: The p.(Val113Ile) mutation results in an alteration of the atypical LCD phenotype associated with the p.(Leu558Pro) mutation. This represents only the second report of the alteration of the phenotype of a TGFBI dystrophy by a second, non-homozygous pathogenic mutation, and thus provides insight into the phenotype-genotype correlation of the TGFBI dystrophies. PMID- 27402971 TI - Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. AB - Treatment options for immune thrombocytopenia (ITP) in pregnancy are limited, and evidence to guide management decisions is lacking. This retrospective study of singleton pregnancies from 2 tertiary centers compared the effectiveness of intravenous immunoglobulin (IVIg) and corticosteroids in treatment of ITP. Data from 195 women who had 235 pregnancies were reviewed. Treatment was not required in 137 pregnancies (58%). Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated with IVIg and 51 were treated with corticosteroids as the initial intervention. Mean maternal platelet count at birth did not differ between groups (IVIg 69 * 10(9)/L vs corticosteroids 77 * 10(9)/L; P = .71) nor did the proportion of mothers who achieved a platelet count response (IVIg 38% vs corticosteroids 39%; P = .85). There were no fatal or severe maternal, fetal, or neonatal hemorrhages. Of 203 neonates in whom platelet counts were available, 56 (28%) had a birth platelet count <150 * 10(9)/L and 18 (9%) had platelet counts <50 * 10(9)/L. Nadir platelet counts for most affected neonates occurred at birth, although for some neonates, nadir platelet counts occurred up to 6 days postnatally. Intracranial hemorrhage was noted in 2 neonates (nadir platelet counts were 135 and 18 * 10(9)/L). There were no neonatal deaths. The majority of pregnant women with a history of ITP did not require treatment, and neonatal outcomes were comparable for mothers who received IVIg or corticosteroids for treatment of maternal ITP. PMID- 27402972 TI - The 12-year follow-up of survival, chronic adverse effects, and retention of arsenic in patients with acute promyelocytic leukemia. PMID- 27402973 TI - tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis. AB - In mammals, embryonic hematopoiesis occurs in successive waves, culminating with the emergence of hematopoietic stem cells (HSCs) in the aorta. HSCs first migrate to the fetal liver (FL), where they expand, before they seed the bone marrow niche, where they will sustain hematopoiesis throughout adulthood. In zebrafish, HSCs emerge from the dorsal aorta and colonize the caudal hematopoietic tissue (CHT). Recent studies showed that they interact with endothelial cells (ECs), where they expand, before they reach their ultimate niche, the kidney marrow. We identified tfec, a transcription factor from the mitf family, which is highly enriched in caudal endothelial cells (cECs) at the time of HSC colonization in the CHT. Gain-of-function assays indicate that tfec is capable of expanding HSC derived hematopoiesis in a non-cell-autonomous fashion. Furthermore, tfec mutants (generated by CRISPR/Cas9) showed reduced hematopoiesis in the CHT, leading to anemia. Tfec mediates these changes by increasing the expression of several cytokines in cECs from the CHT niche. Among these, we found kitlgb, which could rescue the loss of HSCs observed in tfec mutants. We conclude that tfec plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines. The full comprehension of the mechanisms induced by tfec will represent an important milestone toward the expansion of HSCs for regenerative purposes. PMID- 27402974 TI - Anoxia and glucose supplementation preserve neutrophil viability and function. AB - Functional studies of human neutrophils and their transfusion for clinical purposes have been hampered by their short life span after isolation. Here, we demonstrate that neutrophil viability is maintained for 20 hours in culture media at 37 degrees C under anoxic conditions with 3 mM glucose and 32 MUg/mL dimethyloxalylglycine supplementation, as evidenced by stabilization of Mcl-1, proliferating cell nuclear antigen (PCNA), and pro-caspase-3. Notably, neutrophil morphology (nucleus shape and cell-surface markers) and functions (phagocytosis, degranulation, calcium release, chemotaxis, and reactive oxygen species production) were comparable to blood circulating neutrophils. The observed extension in neutrophil viability was reversed upon exposure to oxygen. Extending neutrophil life span allowed efficient transfection of plasmids (40% transfection efficiency) and short interfering RNA (interleukin-8, PCNA, and Bax), as a validation of effective and functional genetic manipulation of neutrophils both in vitro and in vivo. In vivo, transfusion of conditioned neutrophils in a neutropenic guinea pig model increased bacterial clearance of Shigella flexneri upon colonic infection, strongly suggesting that these conditioned neutrophils might be suitable for transfusion purposes. In summary, such conditioning of neutrophils in vitro should facilitate their study and offer new opportunities for genetic manipulation and therapeutic use. PMID- 27402975 TI - Drug previously available only through Cancer Drugs Fund is approved for NHS use. PMID- 27402976 TI - The Challenge of the Accreditation Council for Pharmacy Education's Standard Four: Identifying, Teaching, Measuring. PMID- 27402977 TI - Expanding Dress Code Requirements in the Doctor of Pharmacy Program. AB - Although the use of a professional dress code is standard practice across colleges and schools of pharmacy during introductory and advanced pharmacy practice experiences, requiring professional attire is not applied consistently during the didactic portion of students' education. There are arguments for and against the adoption of a professional dress code throughout the entire doctor of pharmacy program, including the classroom setting. Given uncertainty regarding the potential benefits and challenges that may arise from adopting a professional dress code in the didactic portion of a student pharmacist's education, it is perhaps not surprising that programs adopt disparate policies regarding its use. This exploration was conducted as part of a series of debates held in conjunction with the American Association of Colleges of Pharmacy's (AACP) Academic Leadership Fellows Program (ALFP) and was presented at the 2015 AACP Interim Meeting on February 7, 2015. PMID- 27402978 TI - Insights, Pearls, and Guidance on Successfully Producing and Publishing Educational Research. AB - It is the collaborative responsibility of authors, reviewers, and editors to produce high-quality manuscripts that advance knowledge and educational practice. Experience with manuscript submissions to the American Journal of Pharmaceutical Education reveal several areas for improvement that authors can make to increase their submission success rate during the review process. These improvements include research question justification, improved clarity and details regarding methodology, concise data and results, and a discussion that frames research findings in the context of what is already known. This paper summarizes common flaws we see in submitted manuscripts and makes suggestions on how to address these areas and improve publication success. PMID- 27402979 TI - Students' Perception of Self-Efficacy Following Medicinal Chemistry Skills Laboratory Exercises. AB - Objective. To analyze student perceptions of self-efficacy in meeting medicinal chemistry course related educational outcomes and skills following a medicinal chemistry skills laboratory. Methods. Four activities were implemented in a pharmacy skills laboratory (PSL) for second-year pharmacy students. Students (n=121) worked individually on exercises for three of the four activities. Pre/post-laboratory surveys on self-efficacy were administered. The McNemar test was performed to evaluate students' self-efficacy above 70% related to course outcomes before and after the exercises in each activity. An independent t test was conducted to compare the mean of students' responses on meeting course outcomes based on the 70% anchor for the perspective confidence on meeting course outcomes. Results. The post-PSL scores on all self-efficacy questions improved. The majority of students reported skill development in all exercises. Students and clinical faculty qualitative responses indicated they felt exercises were effective. Conclusion. A PSL can serve as a valuable opportunity to address course related educational outcomes and specific skill development and can help students assess their self-efficacy in meeting them. PMID- 27402980 TI - A Mixed-Methods Analysis in Assessing Students' Professional Development by Applying an Assessment for Learning Approach. AB - Objective. To describe an approach for assessing the Accreditation Council for Pharmacy Education's (ACPE) doctor of pharmacy (PharmD) Standard 4.4, which focuses on students' professional development. Methods. This investigation used mixed methods with triangulation of qualitative and quantitative data to assess professional development. Qualitative data came from an electronic developmental portfolio of professionalism and ethics, completed by PharmD students during their didactic studies. Quantitative confirmation came from the Defining Issues Test (DIT)-an assessment of pharmacists' professional development. Results. Qualitatively, students' development reflections described growth through this course series. Quantitatively, the 2015 PharmD class's DIT N2-scores illustrated positive development overall; the lower 50% had a large initial improvement compared to the upper 50%. Subsequently, the 2016 PharmD class confirmed these average initial improvements of students and also showed further substantial development among students thereafter. Conclusion. Applying an assessment for learning approach, triangulation of qualitative and quantitative assessments confirmed that PharmD students developed professionally during this course series. PMID- 27402981 TI - Professional Organizations for Pharmacy Students on Satellite Campuses. AB - Objective. To evaluate the structure and impact of student organizations on pharmacy school satellite campuses. Methods. Primary administrators from satellite campuses received a 20-question electronic survey. Quantitative data analysis was conducted on survey responses. Results. The most common student organizations on satellite campuses were the American Pharmacists Association (APhA) (93.1%), American Society of Health-System Pharmacists (ASHP) (89.7%), Christian Pharmacists Fellowship International (CPFI) (60.0%), state organizations (51.7%), and local organizations (58.6%). Perceived benefits of satellite campus organizations included opportunities for professional development, student engagement, and service. Barriers to success included small enrollment, communication between campuses, finances, and travel. Conclusion. Student organizations were an important component of the educational experience on pharmacy satellite campuses and allowed students to develop professionally and engage with communities. Challenges included campus size, distance between campuses, and communication. PMID- 27402982 TI - Assessing Opportunities for Student Pharmacist Leadership Development at Schools of Pharmacy in the United States. AB - Objective. To summarize student pharmacist leadership development opportunities delivered by pharmacy programs, to describe selected opportunities, and to assess how these opportunities meet leadership development competencies. Methods. A multi-method study was conducted that comprised a systematic content analysis of pharmacy education journals, pharmacy program websites, and telephone interviews with key informants, which included open-ended questions and scaled responses. Results. Review of six articles, 37 American Association of Colleges of Pharmacy (AACP) Annual Meeting abstracts, and 138 websites resulted in the identification of 191 leadership development opportunities. These consisted of courses, projects/programs, and events/speaker series. Interviews with 12 key informants detailed unique events that developed leadership competencies. Formal assessments of student leadership development were limited and primarily focused on informal feedback and course evaluations. Conclusion. Most US pharmacy programs offer their students an array of opportunities to develop leadership abilities. Pharmacy programs should consider expanding opportunities beyond elective courses, learn from the successes of others to implement new leadership development opportunities, and bolster the assessment of student leadership competencies and outcomes. PMID- 27402983 TI - Impact of a Mental Illness Stigma Awareness Intervention on Pharmacy Student Attitudes and Knowledge. AB - Objective. To determine if exposure to an intervention course impacts pharmacy students' mental health stigma (MHS) and mental health knowledge (MHK). Methods. A one-group pre/posttest intervention study of third-year pharmacy students (N=120) was conducted. Dependent variables were subdomains of MHS (recovery, safety, disclosure, separation, comfort) which were measured on a 5-point Likert scale (1=strongly disagree; 5=strongly agree). Mental health knowledge was measured with 10 true/false questions. The 2.5-hour intervention included presentations, videos, discussions, and active-learning exercises. Pre/posttests were administered, and data were analyzed using paired t tests and McNemar's tests. Results. Among responding students (n=88; 73.3% response rate), the following stigma subdomains significantly decreased after the intervention for depression and schizophrenia: recovery, safety, separation, and comfort. Mental health knowledge scores significantly increased from 5.9 (1.5) to 6.8 (1.5). Conclusion. Pharmacy students' MHS and MHK related to depression and schizophrenia can be improved through a brief and interactive anti-stigma intervention. PMID- 27402984 TI - Impact of Instruction and Feedback on Reflective Responses during an Ambulatory Care Advanced Pharmacy Practice Experience. AB - Objective. To investigate whether instruction and feedback on reflective responses are beneficial in developing pharmacy students to become more reflective practitioners. Methods. Students on an advanced pharmacy practice experience answered weekly reflection questions and were randomly assigned to either an intervention (received instruction and feedback on reflection) or control group. The final week's responses were de-identified and two blinded faculty members independently categorized them as reflective or nonreflective. The primary outcome measure was comparing the number of "reflective" responses in each group. Results. The responses were classified as reflective in 83.3% of students in the intervention group (n=18) compared to 37.5% of the control group (n=16). The odds that the response was categorized as reflective were 8.3 times higher in the intervention group. Conclusion. Providing instruction and feedback to students improved the likelihood that their work was reflective. PMID- 27402985 TI - A Comparative Analysis of Perceptions of Pharmacy Students' Stress and Stressors across Two Multicampus Universities. AB - Objective. To compare perceived levels of stress, stressors, and academic self efficacy among students at two multicampus colleges of pharmacy. Methods. A survey instrument using previously validated items was developed and administered to first-year, second-year, and third-year pharmacy students at two universities with multiple campuses in spring 2013. Results. Eight hundred twenty students out of 1115 responded (73.5% response rate). Institutional differences were found in perceived student stress levels, self-efficacy, and stress-related causes. An interaction effect was demonstrated between institution and campus type (main or branch) for perceived stress and self-efficacy although campus type alone did not demonstrate a direct effect. Institutional and campus differences existed in awareness of campus counseling services, as did a few differences in coping methods. Conclusion. Stress measures were similar for pharmacy students at main or branch campuses. Institutional differences in student stress might be explained by instructional methods, campus support services, institutional climate, and nonuniversity factors. PMID- 27402986 TI - A Comparison of Patient-Centered Care in Pharmacy Curricula in the United States and Europe. AB - Objective. To compare United States and European Higher Education Area (EHEA) undergraduate pharmacy curricula in terms of patient-centered care courses. Methods. Websites from all pharmacy colleges or schools in the United States and the 41 countries in the EHEA were retrieved from the FIP Official World List of Pharmacy Schools and investigated. A random sample of schools was selected and, based on analyses of course descriptions from syllabi, each course was classified into the following categories: social/behavioral/administrative pharmacy sciences, clinical sciences, experiential, or other/basic sciences. Results. Of 147 schools of pharmacy, 59 were included (23 in US and 36 in the EHEA). Differences existed in the percentages of credits/hours in all of the four subject area categories. Conclusion. Institutions in EHEA countries maintain a greater focus on basic sciences and a lower load of clinical sciences in pharmacy curricula compared to the United States. These differences may not be in accordance with international recommendations to educate future pharmacists focused on patient care. PMID- 27402987 TI - Student Characteristics Associated with Successful Matching to a PGY1 Residency Program. AB - Objective. To identify predictors for postgraduate matching success. Methods. In April 2014, a survey was distributed to students at five schools of pharmacy in the United States assessing organizational involvement, research and work experience, postgraduation plans, match status, and demographics. Results. Five hundred seventy-seven students (82%) completed the survey. Applicants who matched had a higher median number of interview offers compared to those who did not match. Significantly more females than males applied for a residency program. Those who matched had a higher median pharmacy school grade point average (GPA) compared to those who did not. No differences were observed in the rates of matching when leadership positions, student organizational membership, or previous work experience were considered. Conclusion. For pharmacy students in this study, number of applications and interviews, pharmacy school GPA, and female gender were associated with a higher likelihood of matching. PMID- 27402988 TI - Designing and Evaluating an Interprofessional Experiential Course Series Involving Medical and Pharmacy Students. AB - Objective. To prepare first-year and second-year pharmacy and medical students to build effective collaborative health care teams by participating in an interprofessional experiential 6-semester course series. Design. An interprofessional experiential course series was designed using a variety of teaching methods to achieve both interprofessional and experiential learning outcomes. A standardized objective behavioral assessment was developed to measure team performance of interprofessional communication and teamwork. In addition, student perceptions were measured using a validated instrument. Assessment. A majority of teams demonstrated appropriate competence with respect to interprofessional communication and teamwork. Additionally, a majority of students expressed positive perceptions of interprofessional collaboration with respect to teamwork, roles and responsibilities, and patient outcomes. Conclusion. An interprofessional experiential course series can be successfully implemented to achieve both interprofessional and experiential learning outcomes. Highly collaborative teams and positive student perceptions provide evidence of achievement of interprofessional education learning outcomes. PMID- 27402989 TI - Using Simulation to Improve First-Year Pharmacy Students' Ability to Identify Medication Errors Involving the Top 100 Prescription Medications. AB - Objective. To evaluate first-year pharmacy students' ability to identify medication errors involving the top 100 prescription medications. Design. In the first quarter of a 3-quarter pharmacy self-care course, a didactic lecture on the most common prescribing and dispensing prescription errors was presented to first year pharmacy students (P1) in preparation for a prescription review simulation done individually and as a group. In the following quarter, they were given a formal prescription review workshop before a second simulation involving individual and group review of a different set of prescriptions. Students were evaluated based on the number of correctly checked prescriptions and a self assessment of their confidence in reviewing prescriptions. Assessment. All 63 P1 students completed the prescription review simulations. The individual scores did not significantly change, but group scores improved from 79 (16.2%) in the fall quarter to 98.6 (4.7%) in the winter quarter. Students perceived improvement of their prescription checking skills, specifically in their ability to fill a prescription on their own, identify prescribing and dispensing errors, and perform pharmaceutical calculations. Conclusion. A prescription review module consisting of a didactic lecture, workshop and simulation-based methods to teach prescription analysis was successful at improving first year pharmacy students' knowledge, confidence, and application of these skills. PMID- 27402990 TI - Using a Virtual Tablet Machine to Improve Student Understanding of the Complex Processes Involved in Tablet Manufacturing. AB - Objective. To develop and implement a virtual tablet machine simulation to aid distance students' understanding of the processes involved in tablet production. Design. A tablet simulation was created enabling students to study the effects different parameters have on the properties of the tablet. Once results were generated, students interpreted and explained them on the basis of current theory. Assessment. The simulation was evaluated using written questionnaires and focus group interviews. Students appreciated the exercise and considered it to be motivational. Students commented that they found the simulation, together with the online seminar and the writing of the report, was beneficial for their learning process. Conclusion. According to students' perceptions, the use of the tablet simulation contributed to their understanding of the compaction process. PMID- 27402992 TI - Bringing More Veterinary Pharmacy into the Pharmacy Curriculum. PMID- 27402991 TI - A Systematic Review of the Effects of Continuing Education Programs on Providing Clinical Community Pharmacy Services. AB - Objective. To summarize the effects of media methods used in continuing education (CE) programs on providing clinical community pharmacy services and the methods used to evaluate the effectiveness of these programs. Methods. A systematic review was performed using Medline, SciELO, and Scopus databases. The timeline of the search was 1990 to 2013. Searches were conducted in English, Portuguese, and Spanish. Results. Nineteen articles of 3990 were included. Fourteen studies used only one media method, and the live method (n=11) was the most frequent (alone or in combination). Only two studies found that the CE program was ineffective or partially effective; these studies used only the live method. Most studies used nonrobust, nonvalidated, and nonstandardized methods to measure effectiveness. The majority of studies focused on the effect of the CE program on modifying the knowledge and skills of the pharmacists. One study assessed the CE program's benefits to patients or clients. Conclusion. No evidence was obtained regarding which media methods are the most effective. Robust and validated methods, as well as assessment standardization, are required to clearly determine whether a particular media method is effective. PMID- 27402993 TI - Annual Report of the Accreditation Council for Pharmacy Education. PMID- 27402994 TI - 117(th) Annual Meeting of the American Association of Colleges of Pharmacy, Anaheim, California, July 23-27, 2016. PMID- 27402995 TI - Drug-Induced QT Interval Prolongation in Children: Are the Kids Alright? PMID- 27402996 TI - [Not Available]. PMID- 27402997 TI - Management of Hospital Formularies in Ontario: Challenges within a Local Health Integration Network. AB - BACKGROUND: Expenditures on drugs dispensed and administered to patients in Canadian hospitals have been estimated at $2.4 billion per year. Pharmacy and therapeutics (P&T) committees play a key role in the evaluation and management of drug therapies in this setting. Hospitals differ with respect to the composition of these committees, their members' expertise, and the processes used for making formulary decisions. OBJECTIVES: To examine the current processes for formulary drug review from the perspective of P&T committees and their individual members, and to examine the needs and preferences of these stakeholders related to evidence review and potential collaborative drug review processes within a large Local Health Integration Network (LHIN) in Ontario. METHODS: Twenty-three sites within 10 hospital corporations in LHIN 4 (Hamilton Niagara Haldimand Brant) were recruited. A 2-part questionnaire was developed and pretested for clarity and comprehensiveness. The institution profile section of the questionnaire was to be completed by pharmacy directors and the P&T section by committee members. RESULTS: Ten pharmacy directors and 28 committee members representing 10 P&T committees responded. A mean of 6.4 new drug requests were reviewed annually by each P&T committee. Across the LHIN, the workload associated with reviewing submissions for new drugs to be added to the formulary represented 0.84 full-time equivalent. The quality of clinical evidence in the drug submissions was rated more favourably than the quality of economic evidence; furthermore, the use of economic evidence was limited by a lack of health economics expertise within the committees. A centralized review process for the LHIN was perceived as beneficial to improve efficiency, the quality of review, and standardization, and also to reduce costs. CONCLUSIONS: Across the Hamilton Niagara Haldimand Brant LHIN, considerable time and resources are spent on the review of potential new drugs for addition to the hospitals' formularies. A standardized formulary review process, with greater use of provincial and national drug reviews, would likely benefit all LHINs. PMID- 27402998 TI - Appropriateness of Dabigatran and Rivaroxaban Prescribing for Hospital Inpatients. AB - BACKGROUND: Recent approval of the new oral anticoagulants dabigatran and rivaroxaban has led to rapid changes in anticoagulant prescribing practices. Postmarketing reports have highlighted safety concerns with these agents, and their use outside of evidence-based recommendations was noted at the authors' centre. OBJECTIVES: To determine the incidence of and risk factors associated with inappropriate prescribing of dabigatran and rivaroxaban. METHODS: This retrospective cohort study investigated randomly selected dabigatran or rivaroxaban prescriptions for patients admitted to a tertiary teaching hospital between January 2010 and December 2012. Appropriateness of prescribing was determined from the documented indication, drug dosage, patient's renal function, and presence of drug interactions, if applicable. RESULTS: Among a total of 321 medication orders reviewed, the incidence of inappropriate use was 31.2% (34/109) for dabigatran and 26.9% (57/212) for rivaroxaban. Of the 97 reasons for inappropriate use that were identified, the most common were prescribing for an unapproved indication (49/97 [50.5%]), concomitant prescribing of another anticoagulant (22/97 [22.7%]), and high prescribed dose (9/97 [9.3%]). The prescribing service was found to be an independent risk factor for inappropriate prescribing (p = 0.041). Corrections were made to 23.1% (21/91) of the incorrect regimens before hospital discharge. In a sensitivity analysis using calculated ideal body weight to estimate renal function, the overall incidence of inappropriate prescribing increased to 31.5% (101/321). CONCLUSIONS: The proportion of patients with inappropriate prescribing of dabigatran or rivaroxaban in clinical practice was higher than expected. Educational interventions and pharmacy-led initiatives with a focus on appropriate indications, concomitant anticoagulant prescribing, and review of dosage regimens are recommended to improve patient safety. PMID- 27402999 TI - Chemotherapy Order Entry by a Clinical Support Pharmacy Technician in an Outpatient Medical Day Unit. AB - BACKGROUND: Pharmacy technicians are expanding their scope of practice, often in partnership with pharmacists. In oncology, such a shift in responsibilities may lead to workflow efficiencies, but may also cause concerns about patient risk and medication errors. OBJECTIVES: The primary objective was to compare the time spent on order entry and order-entry checking before and after training of a clinical support pharmacy technician (CSPT) to perform chemotherapy order entry. The secondary objectives were to document workflow interruptions and to assess medication errors. METHODS: This before-and-after observational study investigated chemotherapy order entry for ambulatory oncology patients. Order entry was performed by pharmacists before the process change (phase 1) and by 1 CSPT after the change (phase 2); order-entry checking was performed by a pharmacist during both phases. The tasks were timed by an independent observer using a personal digital assistant. A convenience sample of 125 orders was targeted for each phase. Data were exported to Microsoft Excel software, and timing differences for each task were tested with an unpaired t test. RESULTS: Totals of 143 and 128 individual orders were timed for order entry during phase 1 (pharmacist) and phase 2 (CSPT), respectively. The mean total time to perform order entry was greater during phase 1 (1:37 min versus 1:20 min; p = 0.044). Totals of 144 and 122 individual orders were timed for order-entry checking (by a pharmacist) in phases 1 and 2, respectively, and there was no difference in mean total time for order-entry checking (1:21 min versus 1:20 min; p = 0.69). There were 33 interruptions not related to order entry (totalling 39:38 min) during phase 1 and 25 interruptions (totalling 30:08 min) during phase 2. Three errors were observed during order entry in phase 1 and one error during order-entry checking in phase 2; the errors were rated as having no effect on patient care. CONCLUSIONS: Chemotherapy order entry by a trained CSPT appeared to be just as safe and efficient as order entry by a pharmacist. Changes in pharmacy technicians' scope of practice could increase the amount of time available for pharmacists to provide direct patient care in the oncology setting. PMID- 27403000 TI - Factors Influencing Fourth-Year Pharmacy Students' Decisions to Pursue a Hospital Pharmacy Residency. AB - BACKGROUND: The Canadian Society of Hospital Pharmacists promotes the recruitment of residency-trained pharmacists for work in hospitals and related health care settings. However, Quebec hospitals are still hiring non-residency trained pharmacists, in part because of a severe shortage of hospital pharmacists. To date, no studies have examined the factors influencing the career choices of fourth-year pharmacy students in Canada. OBJECTIVES: To identify motivating factors and barriers influencing students' decision to pursue a hospital pharmacy residency. METHODS: All 186 fourth-year students in the Faculty of Pharmacy, Universite de Montreal, were invited by e-mail to participate in a validated and institutionally approved survey that was available online between March and May 2014. RESULTS: Of the 138 respondents who returned a completed survey (74% response rate), 36 (26%) planned to apply for a hospital pharmacy residency. Those planning to apply for a residency were older (p = 0.037) and had more hospital work experience (36% versus 3%, p < 0.001) than those not planning to apply. The most important motivators for pursuing a residency were potential gains in knowledge (reported by 88% of respondents, whether or not they were planning to pursue a residency), experience (80%), and self-confidence (62%). The most frequently reported barriers were recognition that a hospital pharmacy residency is a highly demanding program (65%), having work available upon graduation from the undergraduate program (43%), and financial obligations (34%). Hospital experiential rotations influenced, either positively or negatively, 23 (72%) of the 32 students who changed their decision to pursue or not pursue residency training over the course of their studies. CONCLUSIONS: The potential gain in knowledge and experience acquired through residency, the fact that it is considered a highly demanding program, and having work available upon graduation from undergraduate studies were the most influential factors in fourth-year pharmacy students' decision of whether to pursue a hospital pharmacy residency. PMID- 27403001 TI - Causes of Health Care Workers' Exposure to Antineoplastic Drugs: An Exploratory Study. AB - BACKGROUND: The exposure of health care workers to antineoplastic drugs is associated with several adverse health effects, including reproductive toxicities and mutagenic effects. Recent studies have confirmed that Canadian health care workers are at risk of exposure to these agents. However, the causes leading to occupational exposure to antineoplastic drugs are unknown. OBJECTIVE: To perform an exploratory study to ascertain the immediate and contributing causes of health care workers' exposure to antineoplastic drugs. METHODS: Participants were recruited from 6 acute care facilities in Vancouver, British Columbia. Those agreeing to participate were asked to complete a questionnaire about previous exposure to antineoplastic drugs while at work and to describe the circumstances of each exposure incident. Responses were qualitatively analyzed, and the causes of each incident were classified as immediate (unsafe work acts and/or unsafe working conditions) or contributing (related to the management of the organization, the environment, and/or the physical and mental status of the worker). RESULTS: Completed questionnaires were received from 120 participants, 18 (15.0%) of whom reported having had previous occupational exposure to antineoplastic drugs. Qualitative analysis of the responses showed 4 categories of immediate causes (needlestick injury, spill, direct contact, and other unintended exposure) and 3 categories of contributing causes (poor communication, inadequate controls, and lack of training). Some incidents had multiple immediate and/or contributing causes. CONCLUSIONS: According to a review of the immediate and contributing causes identified in this study, many of the exposure incidents were deemed preventable. A "hierarchy of controls" should be implemented, including (in the following order) engineering controls, administrative controls, and personal protective equipment. The findings of this study can be used to develop job safety analyses, which can in turn be adopted in guidelines for safe handling of hazardous drugs. Future similar studies are suggested to ensure the generalizability of results. PMID- 27403002 TI - Domperidone-Associated QT Interval Prolongation in Non-oncologic Pediatric Patients: A Review of the Literature. AB - BACKGROUND: Domperidone is a prokinetic agent used to treat pediatric gastroesophageal reflux disease. Health Canada has issued warnings about an increased risk of domperidone-associated ventricular arrhythmias and sudden cardiac death. However, the supporting data referred only to adult patients; therefore, extrapolating the safety risks to pediatric patients is difficult. OBJECTIVE: To summarize and evaluate the evidence for domperidone-associated QT interval prolongation, ventricular arrhythmias, and sudden cardiac death to determine the safety of this drug for pediatric patients. DATA SOURCES: Two databases (MEDLINE [1946 to August 2015] and Embase [1980 to August 2015]) were searched with the following Medical Subject Headings and keywords: "domperidone", "arrhythmias, cardiac", "death, sudden, cardiac", "electrocardiography", "heart diseases", "long QT syndrome", "tachycardia, ventricular", "torsades de pointes", and "ventricular fibrillation". The search was limited to studies conducted in humans under 18 years of age and published in English. STUDY SELECTION AND DATA EXTRACTION: Original research included in this review reported on the cardiac related safety of domperidone in nononcologic patients under 18 years of age. DATA SYNTHESIS: Of the 5 studies meeting the inclusion criteria (n = 137 patients), one reported a statistically significant change in the corrected QT (QTc) interval, but the clinical significance was unclear. Most of the studies reported rare occurrences of pathological QTc intervals in a limited number of patients. However, confounding factors (e.g., abnormal electrolyte level or concurrent medications) were not consistently considered. Potential bias might have been alleviated by blinding of electrocardiogram (ECG) assessors; however, this was not consistently implemented. The designs of the included studies did not allow assessment of causality. The results should be interpreted with caution. CONCLUSIONS: Although the available evidence is limited, pathological QTc intervals were noted among a small number of infants, which supports the possibility of domperidone-associated risk of prolonged QTc interval. Because of the potential severity of QT interval prolongation, individual assessment and routine ECG monitoring should be implemented for patients receiving domperidone. PMID- 27403003 TI - Pharmacy Practice and the Health Care System in Saudi Arabia. PMID- 27403004 TI - Mycobacterium abscessus Lung Infection: A Case Report. PMID- 27403005 TI - [Not Available]. PMID- 27403006 TI - Should Entry-to-Practice Doctor of Pharmacy (PharmD) Curricula Have at Least One Mandatory Experiential Internship Focusing on Cultural Awareness Training? PMID- 27403007 TI - DPP-4 Inhibitors: The Seinfeld of Oral Antihyperglycemics. PMID- 27403008 TI - Zika Virus: Facts, Prevention Strategies, and an Informed Tourist Perspective. PMID- 27403009 TI - Stability of Ertapenem 100 mg/mL at Room Temperature. PMID- 27403010 TI - [Not Available]. PMID- 27403011 TI - CSHP-An Organization of Volunteers. PMID- 27403012 TI - Predictive performance of BI-RADS magnetic resonance imaging descriptors in the context of suspicious (category 4) findings. AB - OBJECTIVE: To determine the positive predictive value (PPV) and likelihood ratio for magnetic resonance imaging (MRI) characteristics of category 4 lesions, as described in the Breast Imaging Reporting and Data System (BI-RADS((r))) lexicon, as well as to test the predictive performance of the descriptors using multivariate analysis and the area under the curve derived from a receiver operating characteristic (ROC) curve. MATERIALS AND METHODS: This was a double blind review study of 121 suspicious findings from 98 women examined between 2009 and 2013. The terminology was based on the 2013 edition of the BI-RADS. RESULTS: Of the 121 suspicious findings, 53 (43.8%) were proven to be malignant lesions, with no significant difference between mass and non-mass enhancement (p = 0.846). The PPVs were highest for masses with a spiculated margin (71%) and round shape (63%), whereas segmental distribution achieved a high PPV (80%) for non-mass enhancement. Kinetic analyses performed poorly, except for type 3 curves applied to masses (PPV of 73%). Logistic regression models were significant for both patterns, although the results were better for masses, particularly when kinetic assessments were included (p = 0.015; pseudo R(2) = 0.48; area under the curve = 90%). CONCLUSION: Some BI-RADS MRI descriptors have high PPV and good predictive performance-as demonstrated by ROC curve and multivariate analysis-when applied to BI-RADS category 4 findings. This may allow future stratification of this category. PMID- 27403013 TI - Imaging assessment of glenohumeral dysplasia secondary to brachial plexus birth palsy. AB - OBJECTIVE: To assess imaging parameters related to the morphology of the glenohumeral joint in children with unilateral brachial plexus birth palsy (BPBP), in comparison with those obtained for healthy shoulders. MATERIALS AND METHODS: We conducted a retrospective search for cases of unilateral BPBP diagnosed at our facility. Only patients with a clinical diagnosis of unilateral BPBP were included, and the final study sample consisted of 10 consecutive patients who were assessed with cross-sectional imaging. The glenoid version, the translation of the humeral head, and the degrees of glenohumeral dysplasia were assessed. RESULTS: The mean diameter of the affected humeral heads was 1.93 cm, compared with 2.33 cm for those of the normal limbs. In two cases, there was no significant posterior displacement of the humeral head, five cases showed posterior subluxation of the humeral head, and the remaining three cases showed total luxation of the humeral head. The mean glenoid version angle of the affected limbs (90-alpha) was -9.6o, versus +1.6o for the normal, contralateral limbs. CONCLUSION: The main deformities found in this study were BPBP-associated retroversion of the glenoid cavity, developmental delay of the humeral head, and posterior translation of the humeral head. PMID- 27403015 TI - Influence of partial k-space filling on the quality of magnetic resonance images. AB - OBJECTIVE: To study the influence that the scan percentage tool used in partial k space acquisition has on the quality of images obtained with magnetic resonance imaging equipment. MATERIALS AND METHODS: A Philips 1.5 T magnetic resonance imaging scanner was used in order to obtain phantom images for quality control tests and images of the knee of an adult male. RESULTS: There were no significant variations in the uniformity and signal-to-noise ratios with the phantom images. However, analysis of the high-contrast spatial resolution revealed significant degradation when scan percentages of 70% and 85% were used in the acquisition of T1- and T2-weighted images, respectively. There was significant degradation when a scan percentage of 25% was used in T1- and T2-weighted in vivo images (p <= 0.01 for both). CONCLUSION: The use of tools that limit the k-space is not recommended without knowledge of their effect on image quality. PMID- 27403014 TI - Estimating (131)I biokinetics and radiation doses to the red marrow and whole body in thyroid cancer patients: probe detection versus image quantification. AB - OBJECTIVE: To compare the probe detection method with the image quantification method when estimating (131)I biokinetics and radiation doses to the red marrow and whole body in the treatment of thyroid cancer patients. MATERIALS AND METHODS: Fourteen patients with metastatic thyroid cancer, without metastatic bone involvement, were submitted to therapy planning in order to tailor the therapeutic amount of (131)I to each individual. Whole-body scans and probe measurements were performed at 4, 24, 48, 72, and 96 h after (131)I administration in order to estimate the effective half-life (Teff) and residence time of (131)I in the body. RESULTS: The mean values for Teff and residence time, respectively, were 19 +/- 9 h and 28 +/- 12 h for probe detection, compared with 20 +/- 13 h and 29 +/- 18 h for image quantification. The average dose to the red marrow and whole body, respectively, was 0.061 +/- 0.041 mGy/MBq and 0.073 +/- 0.040 mGy/MBq for probe detection, compared with 0.066 +/- 0.055 mGy/MBq and 0.078 +/- 0.056 mGy/MBq for image quantification. Statistical analysis proved that there were no significant differences between the two methods for estimating the Teff (p = 0.801), residence time (p = 0.801), dose to the red marrow (p = 0.708), and dose to the whole body (p = 0.811), even when we considered an optimized approach for calculating doses only at 4 h and 96 h after (131)I administration (p > 0.914). CONCLUSION: There is full agreement as to the feasibility of using probe detection and image quantification when estimating (131)I biokinetics and red-marrow/whole-body doses. However, because the probe detection method is inefficacious in identifying tumor sites and critical organs during radionuclide therapy and therefore liable to skew adjustment of the amount of (131)I to be administered to patients under such therapy, it should be used with caution. PMID- 27403016 TI - Evaluation of different magnetic resonance imaging contrast materials to be used as dummy markers in image-guided brachytherapy for gynecologic malignancies. AB - OBJECTIVE: To identify a contrast material that could be used as a dummy marker for magnetic resonance imaging. MATERIALS AND METHODS: Magnetic resonance images were acquired with six different catheter-filling materials-water, glucose 50%, saline, olive oil, glycerin, and copper sulfate (CuSO4) water solution (2.08 g/L) inserted into compatible computed tomography/magnetic resonance imaging ring applicators placed in a phantom made of gelatin and CuSO4. The best contrast media were tested in four patients with the applicators in place. RESULTS: In T2 weighted sequences, the best contrast was achieved with the CuSO4-filled catheters, followed by saline- and glycerin-filled catheters, which presented poor visualization. In addition (also in T2-weighted sequences), CuSO4 presented better contrast when tested in the phantom than when tested in the patients, in which it provided some contrast but with poor identification of the first dwell position, mainly in the ring. CONCLUSION: We found CuSO4 to be the best solution for visualization of the applicator channels, mainly in T2-weighted images in vitro, although the materials tested presented low signal intensity in the images obtained in vivo, as well as poor precision in determining the first dwell position. PMID- 27403017 TI - Incidental irradiation of internal mammary lymph nodes in breast cancer: conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy. AB - OBJECTIVE: To evaluate incidental irradiation of the internal mammary lymph nodes (IMLNs) through opposed tangential fields with conventional two-dimensional (2D) or three-dimensional (3D) radiotherapy techniques and to compare the results between the two techniques. MATERIALS AND METHODS: This was a retrospective study of 80 breast cancer patients in whom radiotherapy of the IMLNs was not indicated: 40 underwent 2D radiotherapy with computed tomography for dosimetric control, and 40 underwent 3D radiotherapy. The total prescribed dose was 50.0 Gy or 50.4 Gy (2.0 or 1.8 Gy/day, respectively). We reviewed all plans and defined the IMLNs following the Radiation Therapy Oncology Group recommendations. For the IMLNs, we analyzed the proportion of the volume that received 45 Gy, the proportion of the volume that received 25 Gy, the dose to 95% of the volume, the dose to 50% of the volume, the mean dose, the minimum dose (Dmin), and the maximum dose (Dmax). RESULTS: Left-sided treatments predominated in the 3D cohort. There were no differences between the 2D and 3D cohorts regarding tumor stage, type of surgery (mastectomy, breast-conserving surgery, or mastectomy with immediate reconstruction), or mean delineated IMLN volume (6.8 vs. 5.9 mL; p = 0.411). Except for the Dmin, all dosimetric parameters presented higher mean values in the 3D cohort (p < 0.05). The median Dmax in the 3D cohort was 50.34 Gy. However, the mean dose to the IMLNs was 7.93 Gy in the 2D cohort, compared with 20.64 Gy in the 3D cohort. CONCLUSION: Neither technique delivered enough doses to the IMLNs to achieve subclinical disease control. However, all of the dosimetric parameters were significantly higher for the 3D technique. PMID- 27403018 TI - Correlation between effective dose and radiological risk: general concepts. AB - The present review aims to offer an educational approach related to the limitations in the use of the effective dose mgnitude as a tool for the quantification of doses resulting from diagnostic applications of ionizing radiation. We present a critical analysis of the quantities accepted and currently used for dosimetric evaluation in diagnostic imaging procedures, based on studies published in the literature. It is highlighted the use of these quantities to evaluate the risk attributed to the procedure and to calculate the effective dose, as well as to determine its correct use and interpretation. PMID- 27403019 TI - Knee bone tumors: findings on conventional radiology. AB - The knee is a common site for bone tumors, whether clinically painful or not. Conventional radiology has been established as the first line of investigation in patients with knee pain and can reveal lesions that often generate questions not only for the generalist physician but also for the radiologist or general orthopedist. History, image examination, and histopathological analysis compose the essential tripod of the diagnosis of bone tumors, and conventional radiology is an essential diagnostic tool in patients with knee pain. This pictorial essay proposes to depict the main conventional radiography findings of the most common bone tumors around the knee, including benign and malignant tumors, as well as pseudo-tumors. PMID- 27403020 TI - Multidetector computed tomography angiography of the renal arteries: normal anatomy and its variations. AB - Conventional angiography is still considered the gold standard for the study of the anatomy and of vascular diseases of the abdomen. However, the advent of multidetector computed tomography and techniques of digital image reconstruction has provided an alternative means of performing angiography, without the risks inherent to invasive angiographic examinations. Therefore, within the field of radiology, there is an ever-increasing demand for deeper knowledge of the anatomy of the regional vasculature and its variations. Variations in the renal vascular system are relatively prevalent in the venous and arterial vessels. For various conditions in which surgical planning is crucial to the success of the procedure, knowledge of this topic is important. The aim of this study was to familiarize the general radiologist with variations in the renal vascular system. To that end, we prepared a pictorial essay comprising multidetector computed tomography images obtained in a series of cases. We show patterns representative of the most common anatomical variations in the arterial blood supply to the kidneys, calling attention to the nomenclature, as well as to the clinical and surgical implications of such variations. PMID- 27403021 TI - Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer. AB - For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. PMID- 27403022 TI - PET/CT used in the evaluation of pulmonary nodules suspicious for lung cancer in regions where infectious lung disease is endemic: to be or not to be? PMID- 27403023 TI - Neurological symptoms in a case of acute aortic dissection. PMID- 27403024 TI - Use of multislice computed tomography in the diagnosis of annular constrictive pericarditis. PMID- 27403025 TI - Post-Oberlin procedure cortical neuroplasticity in traumatic injury of the upper brachial plexus. PMID- 27403026 TI - Hughes-Stovin syndrome: an unusual cause of pulmonary artery aneurysms. PMID- 27403027 TI - Differential diagnosis of anterior sacral meningocele during the evaluation of post-hysterectomy pelvic collections. PMID- 27403028 TI - Subdividing BI-RADS category 4 breast lesions observed on magnetic resonance imaging: Is it feasible? PMID- 27403029 TI - Imaging evaluation of bone tumors. PMID- 27403030 TI - Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers. AB - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of "liquid biopsy" have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. "Liquid biopsies" represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of "liquid biopsy" as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients. PMID- 27403031 TI - WISP1 Is Increased in Intestinal Mucosa and Contributes to Inflammatory Cascades in Inflammatory Bowel Disease. AB - Inflammatory bowel disease (IBD) is mainly characterized by intestinal tissue damage, which is caused by excessive autoimmune responses poorly controlled by corresponding regulatory mechanisms. WISP1, which belongs to the CCN protein family, is a secreted matricellular protein regulating several inflammatory pathways, such as Wnt/beta-catenin pathway, and has been reported in several diseases including cancer. Here we examined the expression, regulatory mechanisms, and functions of WISP1 in IBD. WISP1 mRNA and protein expression was upregulated in colonic biopsies and lamina propria mononuclear cells (LPMC) of IBD patients compared with those of healthy controls. Tumor necrosis factor- (TNF ) alpha induced WISP1 expression in LPMC from healthy controls. Consistently, WISP1 mRNA expression was downregulated in colonic biopsies from IBD patients who had achieved clinical remission with infliximab (IFX). Furthermore, WISP1 expression was also found to be increased in colons from 2,4,6 trinitrobenzenesulfonic acid- (TNBS-) induced mice compared with those from control mice. Further studies confirmed that administration of rWISP1 could aggravate TNBS-induced colitis in vivo. Therefore, we concluded that WISP1 is increased in IBD and contributes to the proinflammatory cascades in the gut. PMID- 27403032 TI - To Keep or Not to Keep? The Question of Crystallographic Waters for Enzyme Simulations in Organic Solvent. AB - The use of enzymes in non-aqueous solvents expands the use of biocatalysts to hydrophobic substrates, with the ability to tune selectivity of reactions through solvent selection. Non-aqueous enzymology also allows for fundamental studies on the role of water and other solvents in enzyme structure, dynamics, and function. Molecular dynamics simulations serve as a powerful tool in this area, providing detailed atomic information about the effect of solvents on enzyme properties. However, a common protocol for non-aqueous enzyme simulations does not exist. If you want to simulate enzymes in non-aqueous solutions, how many and which crystallographic waters do you keep? In the present work, this question is addressed by determining which crystallographic water molecules lead most quickly to an equilibrated protein structure. Five different methods of selecting and keeping crystallographic waters are used in order to discover which crystallographic waters lead the protein structure to reach an equilibrated structure more rapidly in organic solutions. It is found that buried waters contribute most to rapid equilibration in organic solvent, with slow-diffusing waters giving similar results. PMID- 27403033 TI - Interleukin-27 as a Novel Biomarker for Early Cardiopulmonary Failure in Enterovirus 71-Infected Children with Central Nervous System Involvement. AB - Enterovirus 71 (EV71) is a major pathogen for severe hand, foot, and mouth disease (HFMD), which leads to severe neurological complications and has high morbidity and mortality. Reliable biomarker for the prediction of deterioration in EV71-infected children with central nervous system (CNS) involvement may reduce the cardiopulmonary failure and mortality. Here, we found that serum IL-27 levels were significantly higher in stage III EV71-infected HFMD patients with early cardiopulmonary failure and strong correlation with CRP levels. IL27p28 polymorphisms (rs153109, rs17855750, and rs181206) did not influence IL-27 production, and these three SNPs were not associated with EV71 infection risk and clinical stage. IL-27 can be used as an prediction indicator for early cardiopulmonary failure in EV71-infected children with CNS involvement. PMID- 27403034 TI - Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis. AB - The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-gamma and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID- 27403035 TI - NF-kappaB-Regulated miR-99a Modulates Endothelial Cell Inflammation. AB - Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-kappaB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-alpha, IL-6, IL-1beta, and MCP-1). LPS treatment also inhibited miR 99a production and promoted mTOR expression and NF-kappaB nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-alpha, IL-6, IL-1beta, and MCP-1 overproduction, mTOR upregulation, and NF-kappaB nuclear translocation. The PROMO software analysis indicated NF-kappaB binding site in the -1643 to 1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-kappaB promoted the transcription of miR-99a by binding to the -1643 to -1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-kappaB on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-kappaB signal. NF-kappaB promoted miR-99a production by binding to the -1643 to -1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis. PMID- 27403036 TI - Regulator of Calcineurin 1 in Periodontal Disease. AB - Nuclear factor of activated T-cells (NFAT) and NF-kB pathway associated processes are involved in the pathogenesis of various inflammatory disorders, for example, periodontal disease. The activation of these pathways is controlled by the regulator of calcineurin 1 (RCAN1). The aim of this study was to elucidate the role of RCAN1 in periodontal disease. Healthy and inflamed periodontal tissues were analyzed by immunohistochemistry and immunofluorescence using specific rabbit polyclonal anti-RCAN1 antibodies. For expression analysis human umbilical vein endothelial cells (HUVEC) were used. HUVEC were incubated for 2 h with Vascular Endothelial Growth Factor (VEGF) or with wild type and laboratory strains of Porphyromonas gingivalis (P. gingivalis). Expression analysis of rcan1 and cox2 was done by real time PCR using specific primers for rcan1.4 and cox2. The expression of rcan1 was found to be significantly suppressed in endothelial cells of chronically inflamed periodontal tissues compared to healthy controls. Rcan1 and cox2 were significantly induced by VEGF and wild type and laboratory P. gingivalis strains. Interestingly, the magnitude of the rcan1 and cox2 induction was strain dependent. The results of this study indicate that RCAN1 is suppressed in endothelial cells of chronically inflamed periodontal tissues. During an acute infection, however, rcan1 seems to be upregulated in endothelial cells, indicating a modulating role in immune homeostasis of periodontal tissues. PMID- 27403040 TI - Advanced Reading Comprehension Expectations in Secondary School: Considerations for Students with Emotional or Behavior Disorders. AB - The debate around recent implementation of the Common Core Standards (CCSS) has perplexed many policy makers, practitioners, and researchers; yet there remains broad agreement for the need to improve reading outcomes and college and career readiness for all students, including students with disabilities. One of the most vulnerable populations with disabilities in terms of college and career readiness is students with emotional disorders (ED). A considerable percentage of students with ED encounter unfavorable academic and long-term outcomes, often due to reading difficulties and behavioral variables that impede learning. To date, the impact of rising expectations in reading on the education of students with ED has been absent from this conversation about CCSS. In this article, we consider the implications of new reading expectations in the critical period of Grades 6-12 for students with ED. First, we summarize grade level expectations of the standards. Then, we describe the characteristics and underachievement of students with ED. Next, we evaluate challenges in meeting the expectations based on extant research, and provide recommendations for practice based on the intervention literature. We conclude by prioritizing a research and policy agenda that advocates for increasing the likelihood of success in reading for students with ED in middle school and high school. PMID- 27403038 TI - Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice. AB - Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT(-/-))-mice (n = 8-10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT(-/-)-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2(-/-)-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT(-/-)-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2(-/-)-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID- 27403037 TI - Chemokines and Chemokine Receptors in the Development of Lupus Nephritis. AB - Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN. PMID- 27403039 TI - Role of Porphyromonas gingivalis HmuY in Immunopathogenesis of Chronic Periodontitis. AB - Periodontitis is a multifactorial disease, with participation of bacterial, environmental, and host factors. It results from synergistic and dysbiotic multispecies microorganisms, critical "keystone pathogens," affecting the whole bacterial community. The purpose of this study was to review the role of Porphyromonas gingivalis in the immunopathogenesis of chronic periodontitis, with special attention paid to HmuY. The host response during periodontitis involves the innate and adaptive immune system, leading to chronic inflammation and progressive destruction of tooth-supporting tissues. In this proinflammatory process, the ability of P. gingivalis to evade the host immune response and access nutrients in the microenvironment is directly related to its survival, proliferation, and infection. Furthermore, heme is an essential nutrient for development of these bacteria, and HmuY is responsible for its capture from host heme-binding proteins. The inflammatory potential of P. gingivalis HmuY has been shown, including induction of high levels of proinflammatory cytokines and CCL2, decreased levels of IL-8, and increased levels of anti-HmuY IgG and IgG1 antibodies in individuals with chronic periodontitis. Therefore, the HmuY protein might be a promising target for therapeutic strategies and for development of diagnostic methods in chronic periodontitis, especially in the case of patients with chronic periodontitis not responding to treatment, monitoring, and maintenance therapy. PMID- 27403041 TI - An Open Trial of the Anxiety Action Plan (AxAP): A Brief Pediatrician-Delivered Intervention for Anxious Youth. AB - BACKGROUND: Anxiety disorders in youth are among the most common psychiatric disorders, yet the majority of affected youth do not receive treatment. One approach to improving access to care is identification and intervention within the primary care setting. OBJECTIVE: This manuscript presents data from a single group pre-post open trial of the Anxiety Action Plan (AxAP), a brief pediatrician delivered intervention to reduce anxiety in youth who present in the primary care setting. METHODS: Eleven pediatricians conducted the intervention with 25 youth (mean age 11.16 years; range 6-18 years) with elevated levels of anxiety in their primary care practice setting. RESULTS: Pediatricians' ratings of the AxAP training were positive (mean overall satisfaction was 4.82 on 5 point scale). Pediatricians and parents also reported high levels of intervention satisfaction and acceptability. Parents (but not children) who completed the intervention reported significant reductions from pre- to post-intervention on measures of child anxiety severity, impairment, and caregiver burden (Cohen's d 1.06, .75, .60, respectively). CONCLUSIONS: Findings suggest that a brief, pediatrician delivered intervention in primary care settings appears feasible and beneficial to patients. Additional controlled evaluation of the intervention's efficacy is needed. PMID- 27403042 TI - Minimizing Ports During Robotic Partial Nephrectomy. AB - BACKGROUND AND OBJECTIVE: Robotic upper urinary tract surgery is in most of the cases performed utilizing a standard 5 port configuration. Fewer ports can potentially produce a less invasive operation. Taking in consideration the above we report a novel technique for robot assisted laparoscopic partial nephrectomy utilizing fewer ports and we test its feasibility and safety profile. METHODS: Data on 11 robot-assisted laparoscopic partial nephrectomies performed by using our technique from February 2015 through June 2015 were retrospectively analyzed. The robotic platform used was DaVinci Xi (Intuitive Surgical, Inc., Sunnyvale, California, USA) with a 3-arm setup. The AirSeal system (SurgiQuest, Milford, Connecticut, USA) was used as a port allowing simultaneous introduction of 2 instruments for the bedside surgeon, obviating the need for an additional (fourth) robotic arm. A long suction-and-irrigation device and atraumatic grasping forceps were used. Both instruments were introduced through the trocar of the AirSeal system, making simultaneous introduction and use possible. We preferred the long suction-and-irrigation device, because it minimizes collision of the instruments. RESULTS: Mean age and BMI of the patients were 55 +/-14.6 y and 29.18 +/- 6.85, respectively. Seven tumors were on the right side and 4 were on the left. The mean size of the tumors was 32.45 mm (+/- 11.31). Surgical time was 132.2 minutes (+/-37.17), with an estimated blood loss and ischemia time of 103.63 mL (+/-65.92) and 16.72 minutes (+/-9.52), respectively. One patient had postoperative bleeding that was resolved without transfusion. The median hospitalization period was 3.9 d (+/-0.53). Loss of intra-abdominal pressure was not observed, and pressure was stable at 10 mm Hg. CONCLUSION: The AirSeal System and its valveless trocar eliminated the need for an additional port placement in our series. The technique is feasible, safe, and reproducible; therefore, it may be implemented in selected cases of robot-assisted partial nephrectomies. PMID- 27403043 TI - Erratum. AB - [This corrects the article on p. 1 in vol. 18, PMID: 24680136.]. PMID- 27403044 TI - Optical Enhancement of Exoskeleton-Based Estimation of Glenohumeral Angles. AB - In Robot-Assisted Rehabilitation (RAR) the accurate estimation of the patient limb joint angles is critical for assessing therapy efficacy. In RAR, the use of classic motion capture systems (MOCAPs) (e.g., optical and electromagnetic) to estimate the Glenohumeral (GH) joint angles is hindered by the exoskeleton body, which causes occlusions and magnetic disturbances. Moreover, the exoskeleton posture does not accurately reflect limb posture, as their kinematic models differ. To address the said limitations in posture estimation, we propose installing the cameras of an optical marker-based MOCAP in the rehabilitation exoskeleton. Then, the GH joint angles are estimated by combining the estimated marker poses and exoskeleton Forward Kinematics. Such hybrid system prevents problems related to marker occlusions, reduced camera detection volume, and imprecise joint angle estimation due to the kinematic mismatch of the patient and exoskeleton models. This paper presents the formulation, simulation, and accuracy quantification of the proposed method with simulated human movements. In addition, a sensitivity analysis of the method accuracy to marker position estimation errors, due to system calibration errors and marker drifts, has been carried out. The results show that, even with significant errors in the marker position estimation, method accuracy is adequate for RAR. PMID- 27403045 TI - Patient satisfaction in Dental Healthcare Centers. AB - OBJECTIVES: This study aimed to (1) measure the degree of patient satisfaction among the clinical and nonclinical dental services offered at specialty dental centers and (2) investigate the factors associated with the degree of overall satisfaction. MATERIALS AND METHODS: Four hundred and ninety-seven participants from five dental centers were recruited for this study. Each participant completed a self-administered questionnaire to measure patient satisfaction with clinical and nonclinical dental services. Analysis of variance, t-tests, a general linear model, and stepwise regression analysis was applied. RESULTS: The respondents were generally satisfied, but internal differences were observed. The exhibited highest satisfaction with the dentists' performance, followed by the dental assistants' services, and the lowest satisfaction with the center's physical appearance and accessibility. Females, participants with less than a bachelor's degree, and younger individuals were more satisfied with the clinical and nonclinical dental services. The stepwise regression analysis revealed that the coefficient of determination (R (2)) was 40.4%. The patient satisfaction with the performance of the dentists explained 42.6% of the overall satisfaction, whereas their satisfaction with the clinical setting explained 31.5% of the overall satisfaction. CONCLUSION: Additional improvements with regard to the accessibility and physical appearance of the dental centers are needed. In addition, interventions regarding accessibility, particularly when booking an appointment, are required. PMID- 27403046 TI - Clinical and radiographic comparison of various medicaments used for pulpotomy in primary molars: A randomized clinical trial. AB - OBJECTIVE: To evaluate and compare the efficacy of ferric sulfate, glutaraldehyde, and mineral trioxide aggregate (MTA) as pulpotomy medicaments in primary molars. MATERIALS AND METHODS: This was a perspective randomized clinical trial. A total of 90 molars from 42 children aged 4-8 years were selected for pulpotomy procedure. Teeth were randomly divided into three equal groups of 30 teeth each. Teeth in Group I were intended to be treated with ferric sulfate, Group II were intended to be treated with buffered glutaraldehyde and Group III with MTA. All the molars were evaluated clinically at 24 h and both clinically and radio graphically at 1, 3, and 6 months. The observations were statistically analyzed using Chi-square test and Fisher's exact test. RESULTS: After 1 month, there was no clinical finding observed in all the three groups. At 3 months postoperative evaluation, 13.3% of teeth in Group I and 12.5% of teeth in Group II had mobility. At 6 months interval, pain and sinus formation each was noted in 9.1% of primary teeth in Group I while periodontal ligament widening was reported in 66.7% of teeth in Group I and 85.7% of teeth in Group II. CONCLUSION: MTA exhibited overall best results as pulpotomy agent for primary molars followed by 15.5% ferric sulfate, whereas 2% buffered glutaraldehyde was found to be least effective as a pulpotomy agent. PMID- 27403047 TI - Evaluation of the effect of denture adhesives on surface roughness of two chemically different denture base resins. AB - OBJECTIVE: To evaluate the effect of four commercially available denture adhesives (DAs) on surface roughness of two chemically different denture base materials. MATERIALS AND METHODS: Fifty specimens of heat-cured polymethyl methacrylate, and another fifty specimens of light-cured urethane dimethacrylate were divided into five groups (n = 10), each was immersed in four prepared DAs (Corega Super Cream, Corega Ultra Powder, Olivafix Cream, Protefix Cream) as well as distilled water (control group). The mean surface roughness (R a) of the polished and unpolished surfaces of the specimens was recorded using profilometer device. T-test for paired observation was used to indicate any changes in surface roughness between the baseline and after 30 days of immersion in the DA. RESULTS: Almost all the tested DAs had no significant effect on the roughness of polished and unpolished surfaces of both denture base materials. The Corega super cream DA produced significant increase in the roughness of the polished surfaces of both types of acrylic specimens (P < 0.05). CONCLUSION: The majority of the investigated DAs appears not to affect the surface roughness of denture base materials. Only Corega super cream DA produced detectable increase in the roughness of polished surfaces of denture base specimens. PMID- 27403048 TI - Assessment of post-contamination treatments affecting different bonding stages to dentin. AB - OBJECTIVES: To assess the effect of cleansing treatments following saliva and blood contamination at different bonding stages to dentin. MATERIALS AND METHODS: Labial surfaces of 168 permanent maxillary central incisors were ground flat exposing superficial dentin. Specimens were divided into: uncontaminated control (A), contamination after etching (B), contamination after adhesive application (C), contamination after adhesive polymerization (D). Groups were further subdivided according to cleansing treatments into: rinsing (B1, C1, D1), re etching (B2, D3), sodium hypochlorite application (B3), ethyl alcohol application (C2), acetone application (C3), rinsing and rebonding (D2), re-etching and rebonding (D4). Composite microcylinders were bonded to treated substrates and shear loaded micro-shear bond strength (MUSBS) until failure and treated surfaces were examined with scanning electron microscope. Debonded surfaces were classified as adhesive, cohesive or mixed failure. The data were analyzed using one-way ANOVA and Tukey's post hoc test. RESULTS: The MUSBS values were ranked as follow; Group B: A > B3 > B2 > B1 > B, Group C: A > C3 > C2 > C1 > C, Group D: A > D4 > D1 = D2 >= D3. Debonded surfaces showed adhesive failure in Group B while cohesive failure in Groups C and D. CONCLUSIONS: Cleansing treatments differ according to bonding step; re-etching then rebonding suggested if etched substrate or polymerized adhesive were contaminated while acetone application decontaminated affected unpolymerized adhesive. PMID- 27403049 TI - Effect of cantilever length on stress distribution around implants in mandibular overdentures supported by two and three implants. AB - OBJECTIVE: There is no definitive study comparing stress distribution around two versus three implants in implant-retained overdentures with different cantilever length. The purpose of this finite element study was to evaluate stress pattern around the implants of the 2 or 3 implant- supported mandibular overdenture with different cantilevered length. MATERIALS AND METHODS: The models used in this study were 2 and 3 implant-supported overdenture with bar and clip attachment system on an edentulous mandibular arch. Each model was modified according to cantilever length (0 mm, 7 mm, and 13 mm); thus, 6 models were obtained. The vertical load of 15 and 30 pounds were applied unilaterally to the first molar and 15 pounds to the first premolar, and the stress in bone was analyzed. RESULTS: With increasing cantilever length, no similar stress pattern changes were observed in different areas, but in most instances, an increase in cantilever length did not increase the stress around the implant adjacent to cantilever. CONCLUSIONS: Within the limitations of this study, it can be concluded that increasing of cantilever length in mandibular overdentures retained by 2-3 implants did not cause distinct increasing in stress, especially around the implant adjacent to cantilever, it may be helpful to use cantilever in cases of mandibular overdenture supported by splinted implants with insufficient retention and stability. Based on the findings of this study, optimal cantilever length in mandibular overdenture cannot be determined. PMID- 27403050 TI - Nestin expressions of exposed pulp after direct pulp capping by calcium hydroxide and platelet rich plasma. AB - OBJECTIVE: The aim of this study was to evaluate nestin expression of pulp tissue following direct pulp capping with platelet-rich plasma (PRP). MATERIALS AND METHODS: The thirty sound teeth from Sprague-Dawley rats were used and divided into two groups: Groups 1, teeth were capped with calcium hydroxide/Ca(OH)2 (n = 15) and Group 2 with PRP (n = 15). After 1(st), 7(th), and 21(st) days, respectively, 5 teeth each group (American Dental Association 41) were processed for light microscopic examination. Expressions of nestin were assessed by immunohistochemical techniques. RESULTS: Nestin expression of Ca(OH)2 on the distance place of exposure at 1(st) and 7(th) days were 80% and at 21(st) day were 60%. Nestin expression of PRP on the distance place at 1(st) day was 80%, 7(th) 100%, and 21(st) day was 80%. At day 21 observation, Kruskal-Wallis test shows nestin expression was increased significantly in PRP groups (P < 0.05), but it was not increase significantly compare with Ca(OH)2. CONCLUSION: PRP had ability as a direct pulp capping material to induce nestin expression. PMID- 27403051 TI - Frequency of sucrose exposure on the cariogenicity of a biofilm-caries model. AB - OBJECTIVE: Although sucrose is considered the most cariogenic carbohydrate in the human diet, the question of how many exposures are needed to induce damage on the hard dental tissues remains unclear. To approach this question, different frequencies of daily sucrose exposure were tested on a relevant biological caries model. MATERIALS AND METHODS: Biofilms of the Streptococcus mutans were formed on enamel slabs and exposed to cariogenic challenges with 10% sucrose for 5 min at 0, 1, 3, 5, 8, or 10 times per day. After 5 days, biofilms were retrieved to analyze biomass, protein content, viable bacteria, and polysaccharide formation. Enamel demineralization was evaluated by percentage of microhardness loss (percentage surface hardness loss [%SHL]). RESULTS: Biomass, protein content, polysaccharide production, acidogenicity of the biofilm, and %SHL proportionally increased with the number of daily exposures to sucrose (P < 0.05). One daily sucrose exposure was enough to induce 20% more demineralization than the negative unexposed control. Higher frequencies induced greater demineralization and more virulent biofilms, but eight and ten exposures were not different between them in most of the analyzed variables (P > 0.05). CONCLUSIONS: Higher sucrose exposure seems to increase cariogenicity, in a frequency-dependent manner, by the modification of bacterial virulent properties. PMID- 27403052 TI - Effect of bracket base design on shear bond strength to feldspathic porcelain. AB - OBJECTIVES: This study sought to assess the effect of bracket base design on the shear bond strength (SBS) of the bracket to feldspathic porcelain. MATERIALS AND METHODS: This in vitro, experimental study was conducted on 40 porcelain-fused-to metal restorations and four different bracket base designs were bonded to these specimens. The porcelain surfaces were etched, silanized, and bonded to brackets. Specimens were thermocycler, incubated for 24 h and were subjected to SBS. Data were analyzed using Shapiro-Wilk test, Levene's test, one-way ANOVA, and Tukey's honest significant difference test. Adhesive remnant index was calculated and compared using Fisher's exact test. RESULTS: One-way ANOVA showed that the SBS values were significantly different among the four groups (P < 0.001). Groups 1, 2, and 4 were not significantly different, but group 3 had significantly lower SBS (P < 0.001). Fractures mostly occurred at the porcelain-adhesive interface in Groups 1 and 2 while in Groups 3 and 4, bracket-adhesive and mixed failures were more common. CONCLUSION: The bracket base design significantly affects the SBS to feldspathic porcelain. PMID- 27403053 TI - Dental care provided to sickle cell anemia patients stratified by age: A population-based study in Northeastern Brazil. AB - OBJECTIVE: To assess differences in the dental care provided to sickle cell anemia (SCA) patients depending on age. This retrospective study used secondary data from the dental records of the Center of Hematology and Hemotherapy in Maranhao (HEMOMAR). MATERIALS AND METHODS: Data were obtained from 574 dental records of patients with SCA treated or under treatment in the Dental Department of HEMOMAR from 2000 to 2011. Data on the gender, age, duration of dental treatment, number of patients submitted to periodontal treatment (PT), number of filled teeth (FT), teeth extracted (EX), endodontically treated teeth (ET), and reason for the dental procedures were collected. The Kruskal-Wallis test together with Dunn's post hoc test, Chi-square test, and Spearman's correlation was used for statistical analysis. An alpha error of 5% was considered acceptable. RESULTS: Significant differences were found for FT, EX (P < 0.05), ET and PT (P < 0.001) between the age groups. There were fewer FT in children compared to other age groups (P < 0.001). The most common reasons for restorations and endodontic treatment were dental caries (100%) and irreversible pulpitis (55.6%), respectively. The main reasons for teeth extractions were residual roots (21.3%), chronic apical periodontitis (19.7%), and crown destruction (19.3%). There were positive correlations between age and EX (r = 0.93; P = 0.025) and ET (r = 0.92; P = 0.028). CONCLUSIONS: FT, ET, EX, and PT procedures become more common in older patients. Tooth decay is the main reason for dental treatment in SCA patients. PMID- 27403054 TI - Effects of staining and bleaching on a nanohybrid composite with or without surface sealant. AB - OBJECTIVE: The effect of different staining solutions and a bleaching procedure on color stability and surface roughness of a nanohybrid resin composite were evaluated with or without liquid resin polishing (RP). MATERIALS AND METHODS: Ninety-six disc-shaped resin composite specimens (A1 Shade, Z550 Filtek 3M ESPE, St. Paul, MN, USA) were prepared and divided randomly into two groups (n = 48). Liquid RP (BisCover LV, Bisco Inc., Schaumburg, IL, USA) was applied in one group (RP) and not in the other (P). Specimen color and surface roughness were determined using a colorimeter and profilometer, respectively. After baseline measurements, each group was divided into four subgroups (n = 12) for immersion in a control (distilled water) or three different staining solutions (ice tea, red wine, and cola) for 1 week. Color and surface roughness were then reevaluated. After measurements, all specimens were bleached using a 35% hydrogen peroxide gel. The color and surface roughness of the specimens were reevaluated. STATISTICAL ANALYSIS: Data were subjected to an analysis of variance for repeated measurements among the groups (P < 0.05). RESULTS: Staining and bleaching did not change the surface roughness of the RP and P groups (P > 0.05). Discoloration in the red wine group was higher than for the other staining solutions for the RP (P < 0.001) and P groups (P = 0.018). CONCLUSION: Application of liquid RP did not enhance the color stability and surface roughness of the composite resin restoration. PMID- 27403055 TI - In vitro comparison of antibacterial properties of bioceramic-based sealer, resin based sealer and zinc oxide eugenol based sealer and two mineral trioxide aggregates. AB - OBJECTIVE: Our goal of the study was to evaluate the antibacterial properties of endodontic sealers against the E. faecalis. MATERIALS AND METHODS: Six millimeters wells were made for each material in all the preinoculated petri plates. Then, the petri plates were incubated for 24 h. The zones of inhibition appeared were measured, and the measurements were put to statistical analysis. RESULTS: EndoSequence BC Sealer, MM-mineral trioxide aggregate (MTA), and ProRoot MTA showed maximum means of diameter of zones of inhibition, whereas MM-seal and Endoseal did not show any zones of inhibition. CONCLUSION: EndoSequence BC Sealer was found to be a better endodontic sealer as compared to resin-based and zinc oxide-eugenol-based sealer. PMID- 27403057 TI - Role of enamel deminerlization and remineralization on microtensile bond strength of resin composite. AB - OBJECTIVE: This study is aimed to establish the microtensile bond strength of enamel following exposure to an aerated drink at various time intervals with/without application of remineralization agent. In addition, degree of remineralization and demineralization of tooth enamel has been assessed using polarized light microscopy. MATERIALS AND METHODS: Seventy extracted human incisors split into two halves were immersed in aerated beverage (cola drink) for 5 min and stored in saliva until the time of microtensile bond testing. Prepared specimens were divided randomly into two study groups; remineralizing group (n = 70): specimens were treated for remineralization using casein phosphopeptides and amorphous calcium phosphate (CPP-ACP) remineralization agent (RecaldentTM; GC Europe) and control group (n = 70): no remineralization treatment; specimens were kept in artificial saliva. All specimens were tested for microtensile bond strength at regular intervals (1 h, 1 days, 2 days, 1 week, and 2 weeks) using a universal testing machine. The results statistically analyzed (P = 0.05) using two-way ANOVA test. RESULTS: Results showed statistically significant increase in bond strength in CPP-ACP tested group (P < 0.05) at all-time intervals. The bond strength of remineralizing group samples at 2 days (~13.64 megapascals [MPa]) is comparable to that of control group after 1 week (~12.44 MPa). CONCLUSIONS: CPP ACP treatment of teeth exposed to an aerated drink provided significant increase in bond strength at a shorter interval compared to teeth exposed to saliva alone. PMID- 27403056 TI - Evaluation of the bond strength of root-end placed mineral trioxide aggregate and Biodentine in the absence/presence of blood contamination. AB - OBJECTIVE: Mineral trioxide aggregate (MTA) has been accepted as an appropriate root-end filling material in endodontic microsurgery because of setting ability in the wet environment. The aim of this study was to assess the bond strength of root-end placed MTA and Biodentine (Septodont, Saint Maur des Fosses, France) in the absence/presence of blood contamination. MATERIALS AND METHODS: Forty-eight single-rooted maxillary incisors were used. subsequent to root-end resection and apical preparation using ultrasonic retro-tips, the specimens were randomly separated into two groups according to the root-end filling materials: MTA (Cerkamed Medical Company, Stalowa, Poland) or Biodentine. The specimens were then separated into two subgroups according to storage condition (absence/presence of blood) (n = 12). After obtaining 2.0 +/- 0.1 mm slices, push out tests were performed. Each slice was examined under a stereomicroscope to evaluate the failure mode. The data were analyzed using two-way analysis of variance and Tukey's post hoc test for multiple comparisons. The failure modes were analyzed using the Chi-square test (P = 0.05). RESULTS: The bond strength was significantly affected by the presence of blood contamination and root-end filling material type (P < 0.001). Biodentine had better bond strength than MTA (P < 0.001). The most common failure type was adhesive failure. According to the Chi-square test, there were no statistically significant differences among the groups (P = 0.394). CONCLUSIONS: Biodentine had better bond strength values compared to MTA, and the bond strength of both MTA and Biodentine as root-end filling materials was negatively affected by the presence of blood. PMID- 27403059 TI - Chemomechanical caries removal method versus mechanical caries removal methods in clinical and community-based setting: A comparative in vivo study. AB - OBJECTIVE: To compare the effectiveness of various caries removal techniques in mandibular primary molars using Smart Burs, atraumatic restorative technique (ART) (mechanical caries removal) and Carie-care (chemomechanical caries removal [CMCR]) among primary school children in clinical and community-based settings. MATERIALS AND METHODS: A total of 80 carious primary mandibular molars were selected for the study from the dental clinic and community. They were equally assigned to four groups according to caries removal technique and also by the operating site. In Group 1, caries was removed using Carie-care in the dental clinic and in Group 2, with Smart Burs in the dental clinic. In Group 3, caries was removed using Carie-care in the field and in Group 4, with the ART in the field. The time taken for caries removal, the efficacy of caries removal and patient acceptance were evaluated with different caries removal techniques. STATISTICAL ANALYSIS: The obtained data were subjected to statistical analysis by ANOVA test. RESULTS: In clinical settings, Carie-care was time-consuming but was more efficient with increased acceptance than Smart Burs and the result was found to be significant statistically (P < 0.05). In community-based settings, Carie care was more efficient, less time consuming, and showed an increased acceptance when compared to atraumatic restorative treatment and the result was found to be significant statistically (P < 0.05). CONCLUSIONS: The CMCR technique was superior to the mechanical caries removal technique in primary teeth among school children in terms of time, efficacy, and acceptance in both clinical- and community-based settings. PMID- 27403058 TI - Efficiency of gaseous ozone in reducing the development of dry socket following surgical third molar extraction. AB - OBJECTIVE: The objective of this study was to assess the efficacy of ozone gas (O3) on the reduction of dry socket (DS) occurrence following surgical extraction of lower jaw third molars, influence of the indication for the extraction, and the difficulty of extraction on the incidence of DS. MATERIALS AND METHODS: This study included thirty patients with bilaterally impacted third molars of mandible requiring surgical procedure for extraction. Following extraction, in the control group, saline solution was used for irrigation of extraction sockets and in the experimental group, intra-alveolar O3 was applied for 12 s (Prozone, W and H, UK, Ltd.). The surgeries were performed by the same oral surgeon. The follow-up visits were performed at 48 h and on day seven, postsurgery where the symptoms of DS were evaluated and intensity of pain has been recorded using visual analog scale 0-100. RESULTS: In this pilot study, DS was present in 16.67% and 3.33% of cases in the control and experimental groups, respectively (P = 0.20). CONCLUSION: The application of O3 may reduce the incidence of DS and accelerates the recovery period after the surgery. Prophylactic use of O3 may be suggested in all patients, especially in the patients at a risk of development of DS. PMID- 27403060 TI - The prevalence and distribution of nonsyndromic hyperdontia in a group of Qatari orthodontic and pediatric patients. AB - OBJECTIVE: There is no data specific to the Qatari population on the prevalence and distribution of hyperdontia. The aim of this study was to investigate the prevalence and distribution of hyperdontia in the permanent teeth among a group of Qatari sample and to compare the present results with findings from other populations. MATERIALS AND METHODS: Records of 1269 Qatari patients (674 females; mean age 11.8 +/- 2.3 and 595 males; mean age 11.4 +/- 2.2 years) which included panoramic radiographs were examined to identify hyperdontia in the permanent dentition. Supernumerary teeth were assessed for their location, morphology, number, and whether impacted or not. RESULTS: The prevalence of hyperdontia was 1.6% (females 0.7% and males 0.9%; P < 0169). The most common type of supernumerary teeth was the supplemental (45.5%), followed by the conical (40%). Of the supplemental teeth, the mandibular incisor was the most prevalent (60%), followed by the premolar (20%). No significant difference in the prevalence was found between the maxilla and mandible. More than half of supernumerary teeth identified were impacted (54.5%). CONCLUSIONS: The prevalence of hyperdontia in a group of Qatari population was within the normal range of the majority of published studies in the literature. Although not significant, hyperdontia cases were more prevalent in male patients. PMID- 27403061 TI - Esthetic impact of gingival plastic surgery from the dentistry students' perspective. AB - OBJECTIVE: The aim of the this study was to evaluate the perception of smile esthetics and alterations in cases of gingival plastic surgery for correction of a gummy smile, by means of alterations in smile photograph among dentistry degree students. MATERIALS AND METHODS: A frontal smile photograph of a 40-year-old woman having normal occlusion was used with diverse compositions of gingival exposure level and crown length of maxillary teeth. The eight photographs were evaluated by 216 dentistry students in five class groups (1(st), 2(nd), 3(rd), 4(th) and 5(th) classes). RESULTS: The results revealed that almost all of the class' students perceived differences between images, additionally, the highest percentage of students that answered "no difference" was 12% at 1(st) class' students. 1(st) and 2(nd) class' students most liked photograph which is 2.5 mm gingival display and 3(rd) class students liked two different photographs which are 2.5 mm gingival display and 2 mm gingival display whereas 4(th) class students preferred two different photographs which are 1.5 mm gingival display and 1 mm gingival display, 5(th) class students preferred photograph which is 1.5 mm gingival display as the most. CONCLUSION: Esthetic perception of smile improve as a student passes to higher study classes in terms of gingival exposure. The harmonious display of gingiva exhibits an important effect in the smile esthetics rather than reduced or excessive display. PMID- 27403062 TI - Tooth discoloration induced by a novel mineral trioxide aggregate-based root canal sealer. AB - OBJECTIVES: The aim of this study was to evaluate tooth discoloration caused by contact with a novel injectable mineral trioxide aggregate (MTA)-based root canal sealer (Endoseal; Maruchi, Wonju, Korea) compared with a widely used resin-based root canal sealer (AHplus; Dentsply De Trey, Konstanz, Germany) and conventional MTA (ProRoot; Dentsply, Tulsa, OK, USA). MATERIALS AND METHODS: Forty standardized bovine tooth samples were instrumented and divided into three experimental groups and one control group (n = 10/group). Each material was inserted into the cavity, and all specimens were sealed with a self-adhesive resin. Based on CIE Lab system, brightness change (DeltaL) and total color change (DeltaE) of each specimen between baseline and 1, 2, 4, and 8 weeks were obtained. RESULTS: At all time points, Endoseal showed no significant difference in DeltaL and DeltaE compared to AHplus and control group (P > 0.05), whereas the ProRoot group showed significantly higher DeltaL and DeltaE values than the Endoseal group at 2, 4, and 8 weeks (P < 0.05). Therefore, Endoseal showed less discoloration than conventional MTA and a similar color change to AHplus. CONCLUSIONS: Within the limitations of this study, our data indicate that the MTA based sealer produces a similar amount of tooth discoloration as AHplus which is considered to be acceptable. PMID- 27403063 TI - Comparative in vitro study of the effectiveness of Green tea extract and common storage media on periodontal ligament fibroblast viability. AB - OBJECTIVE: Green tea extract (GTE) was shown to be effective in preserving periodontal ligament fibroblasts (PDLFs) of avulsed teeth. This study aimed at determining the potential of GTE in preserving the viability of PDLFs comparing with different storage media. MATERIALS AND METHODS: Periodontal ligament cells were obtained from freshly extracted healthy impacted third molars and cultured in Dulbecco's Modified Eagle Medium (DMEM). Cell viability was determined by storing the cells in seven media; DMEM, tap water, Hank's balanced salt solution (HBSS), whole milk, hypotonic sucrose solution, GTE, and GTE + sucrose for 1, 2, 4, and 24 h at 37 degrees C using tetrazolium salt-based colorimetric (3-[4, 5 dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. Statistical analysis was performed by one-way analysis of variance and post hoc tests. RESULTS: GTE showed significantly higher protective effect than HBSS at 2, 4, and 24 h (P = 0.009, P = 0.02, P = 0.016), DMED at 2 h (P = 0.003), and milk at 4 h (P = 0.039). CONCLUSION: Although with undesirable osmolality and pH, GTE had a good ability in preserving the PDLFs comparing with other studied media. PMID- 27403064 TI - Biomechanics of cervical tooth region and noncarious cervical lesions of different morphology; three-dimensional finite element analysis. AB - OBJECTIVE: The present study aims to investigate the influence of presence and shape of cervical lesions on biomechanical behavior of mandibular first premolar, subjected to two types of occlusal loading using three-dimensional (3D) finite element method (FEM). MATERIALS AND METHODS: 3D models of the mandibular premolar are created from a micro computed tomography X-ray image: model of sound mandibular premolar, model with the wedge-shaped cervical lesion (V lesion), and model with saucer-shaped cervical lesion (U lesion). By FEM, straining of the tooth tissues under functional and nonfunctional occlusal loading of 200 (N) is analyzed. For the analysis, the following software was used: CTAn program 1.10 and ANSYS Workbench (version 14.0). The results are presented in von Mises stress. RESULTS: Values of calculated stress in all tooth structures are higher under nonfunctional occlusal loading, while the functional loading is resulted in homogeneous stress distribution. Nonfunctional load in the cervical area of sound tooth model as well as in the sub-superficial layer of the enamel resulted with a significant stress (over 50 [MPa]). The highest stress concentration on models with lesions is noticed on the apex of the V-shaped lesion, while stress in saucer U lesion is significantly lower and distributed over wider area. CONCLUSION: The type of the occlusal teeth loading has the biggest influence on cervical stress intensity. Geometric shape of the existing lesion is very important in the distribution of internal stress. Compared to the U-shaped lesions, V-shaped lesions show significantly higher stress concentrations under load. Exposure to stress would lead to its progression. PMID- 27403065 TI - Uses of electromyography in dentistry: An overview with meta-analysis. AB - OBJECTIVE: The purpose of this study was to review the uses of electromyography (EMG) in dentistry in the last few years in related research. EMG is an advanced technique to record and evaluate muscle activity. In the previous days, EMG was only used for medical sciences, but now EMG playing a tremendous role in medical as well as dental sector. MATERIALS AND METHODS: Several electronic databases such as Google Scholar, PubMed, Science Direct, and Web of Science were systematically searched for studies published until July 2015. RESULTS: EMG can be used in both diagnosis and treatment purpose to record neuromuscular activity. In dentistry, we can utilize EMG to evaluate muscular activity in function such as chewing and biting or parafunctional activities such as clenching and bruxism. In case of TMJ and myofascial pain disorders, EMG widely is used in the last few years. CONCLUSIONS: EMG is one of biometric tests that occur in the modern evidence-based dentistry practice. PMID- 27403066 TI - Full-mouth rehabilitation of Class II deep-bite patient: A 5-year clinical report. AB - This case report demonstrates the full-mouth rehabilitation of a 45-year-old male patient with severe deep-bite by increasing vertical dimension. The technique of anterior maxillary osteotomy performed in the present situation has been found to be effective, requiring anterior and inferior repositioning of the anterior maxilla to provide an esthetic and functional implant supported fixed prosthesis. Four months after surgery, the fixation system was removed, and 6 dental implants were placed. The anterior and inferior movements of the segment allowed for natural tooth anatomy and size in the definitive implant supported partial fixed prosthesis. A satisfactory functional and esthetic result was obtained after 5 years of follow-up. PMID- 27403067 TI - Free gingival grafting procedure after excisional biopsy, 12-year follow-up. AB - The total removal of a lesion via excisional biopsy causes gingival recession, resulting in dentin hypersensitivity and esthetical problems. In this case report, a gingival recession defect resulting from an excisional biopsy was treated with a free gingival grafting procedure performed during the same appointment, and its 12-year follow-up was presented. A 44-year-old female patient was presented to our clinic with a firm, pedunculated, red gingival enlargement located on the labial surface of lower incisors. The exposed root surface, after the excisional biopsy, was covered with a free gingival graft. The lesion was pathologically diagnosed as pyogenic granuloma, and in the early postoperative phase, no recurrence was observed, but partial root coverage was determined. At 6-month follow-up, root coverage resulting from "creeping attachment" was observed, and this situation was maintained throughout the 12 year follow-up period. Repetitious postoperative discomfort and emotional stress for the patient may be avoided with a timesaving single appointment performing excisional biopsy and free gingival graft. Free gingival grafting procedure was used for this purpose not only to cover exposed root surfaces but also to eliminate dentin hypersensitivity and make oral hygiene procedures more effective. PMID- 27403068 TI - A modified presurgical orthopedic (nasoalveolar molding) device in the treatment of unilateral cleft lip and palate. AB - Nasoalveolar molding (NAM) can be done effectively to reshape the nasal cartilage and mold the maxillary dentoalveolar arch before surgical cleft lip repair and primary rhinoplasty. Presurgical NAM helps as an adjunct procedure to enhance the esthetic and functional outcome of the surgical procedures. We have developed a modified NAM device to suit to the needs of the patients coming from distant places for the treatment. This device helps in reducing the number of frequent visits the patient needs to take to the craniofacial center. The purpose of this presentation is to report this treatment technique and discuss its application. PMID- 27403069 TI - The maxillary molar endodontic access opening: A microscope-based approach. AB - This article reviews the basic clinical techniques of performing a maxillary molar endodontic access opening, starting from the initial access opening into the pulp chamber, to the point where a size #10 file has been advanced to the apices of all three or four (or more) canals. The article explains how the use of the dental surgical operating microscope or microscope-level loupes magnification of *6-8 or greater, combined with head-mounted or coaxial illumination, improve the ability of a dentist to identify microscopic root canal orifices, which facilitates the efficient creation of conservative access openings with adequate straight-line access in maxillary molars. Magnified photos illustrate various microscopic anatomical structures or landmarks of the initial access opening. Techniques are explored for implementing an access opening for teeth with vital versus necrotic pulpal tissues. The article also explores the use of piezoelectric or ultrasonic instruments for revealing root canal orifices and for removing pulp stones or calcified pulpal tissue inside the pulp chamber. PMID- 27403071 TI - Effect of chorionic villus sampling on the occurrence of preeclampsia and gestational hypertension: An updated systematic review and meta-analysis. AB - OBJECTIVE: To perform a meta-analysis for an assessment of the risk of preeclampsia or gestational hypertension following chorionic villus sampling (CVS). DATA SOURCE: PubMed was systematically searched from its inception through January 2016. MATERIAL AND METHODS: Nine reports were identified. A pre-specified scale was used to assess their quality. TABULATION INTEGRATION AND RESULTS: We performed pooling into three subgroups with respect to the control group: A) Patients with no invasive prenatal diagnostic procedure served as a control group for comparison. The odds ratios for gestational hypertension (0.76, 95% CI 0.46 1.26), preeclampsia (0.83, 95% CI 0.42-1.67), and severe preeclampsia (0.49, 95% CI 0.04-5.78) or when hypertension categories were pooled (0.80, 95% CI 0.46 1.41) were not significantly different. B) Patients with midtrimester diagnostic amniocentesis and patients with no invasive prenatal diagnostic procedure were combined as a control group for comparison. The odds ratios for preeclampsia (1, 95% CI 0.46-2.18), severe preeclampsia (0.83, 95% CI 0.14-4.85), and pooled hypertension categories (1.07, 95% CI 0.63-1.84) were not significantly different. C) Patients with midtrimester diagnostic amniocentesis served as a control group. There was a significant difference in the odds ratio for preeclampsia between the CVS and amniocentesis groups (2.47, 95% CI 1.14-5.33). There was a marginal difference in the odds ratio for combined pregnancy-induced hypertension categories between the CVS and amniocentesis groups (1.61, 95% CI 1.02-2.53). CONCLUSION: The available data do not indicate an increased risk of preeclampsia or gestational hypertension following first trimester CVS. The heterogeneity and retrospective design of existing studies are limiting factors for our analysis and findings. PMID- 27403070 TI - The impact of a simulation-based training lab on outcomes of hysterectomy. AB - OBJECTIVE: To evaluate the impact of a simulation-based training lab on surgical outcomes of different hysterectomy approaches in a resident teaching tertiary care center. MATERIAL AND METHODS: This retrospective cohort study was conducted at The University of Texas, Department of Obstetrics and Gynecology. In total, 1397 patients who had undergone total abdominal hysterectomy (TAH), vaginal hysterectomy (VH), total laparoscopy-assisted hysterectomy (TLH), or robot assisted hysterectomy (RAH) for benign gynecologic conditions between 2009 and 2014 were included in the study. The comparison was made according to the year when the surgeries were performed: 2009 (before simulation training) and the combination of 2010-2014 (after simulation training) for each technique (TAH, VH, and LAH). Since a simulation lab for robotic surgery was introduced in 2010 at our institute, the comparison for robotic surgery was made between the combination of 2009-2010 as the control and the combination of 2010-2014 as the study group. RESULTS: The average estimated blood loss before and after simulation-based training was significantly different in TAH and RAH groups (317+/-170 mL versus 257+/-146 mL, p=0.003 and 154+/-107 mL versus 102+/-88 mL, p=0.004, respectively), but no difference was found for TLH and VH. The mean of length of hospital stay was significantly different before and after simulation based training for each technique: 3.7+/-2.3 versus 2.9+/-2.2 days for TAH, 2.0+/ 1.2 versus 1.3+/-0.9 days for VH, 2.4+/-1.3 versus 1.9+/-2.5 days for TLH, and 2.0+/-1.3 versus 1.4+/-1.7 days for RAH (p<0.01). CONCLUSION: Based on our data, simulator-based training may play an integrative role in developing the residents' surgical skills and thus improving the surgical outcomes of hysterectomy. PMID- 27403072 TI - Primary peritoneal cancer in BRCA carriers after prophylactic bilateral salpingo oophorectomy. AB - OBJECTIVE: The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. Primary peritoneal cancer is an aggressive malignancy which, due to the absence of a specific screening test, cannot be diagnosed in its early stages. As a risk reducing option, prophylactic bilateral salpingo-oophorectomy and mastectomy are often proposed in BRCA gene carriers. The effectiveness of a preventive surgical treatment is, however, unclear in the development of peritoneal cancer. MATERIAL AND METHODS: An extensive electronic search was performed in PubMed, Scopus, and Cochrane databases. RESULTS: The total number of patients who underwent prophylactic bilateral salpingo-oophorectomy was 1,830, of whom 28 presented with peritoneal cancer (1.53%). The age of the included patients ranged from 48 to 61 years. BRCA-1 was present in 9 out of 28 patients and BRCA-2 in 2 patients, while the type of BRCA was unclear in 17 patients. Salpingo-oophorectomy was performed in 23 out of 28 patients, while oophorectomy was carried out in 5 patients. The interval from initial risk-reducing surgical treatment to the presentation of peritoneal cancer ranged from 12 to 84 months. CONCLUSION: Modification of the follow-up guidelines and increase in healthcare providers' awareness may reduce the risk of peritoneal cancer. PMID- 27403073 TI - BRCA1 and BRCA2 sequence variations detected with next-generation sequencing in patients with premature ovarian insufficiency. AB - OBJECTIVE: Although the association between BRCA1 and BRCA2 gene mutations and breast and ovarian cancer is known, there is insufficient data about premature ovarian insufficiency (POI). However, several studies have reported that there might be a relationship between POI and BRCA1 and BRCA2 gene mutation. Therefore, in the present study, we aimed to investigate the role of BRCA1 and BRCA2 gene mutations in the etiology of POI in a Turkish population. MATERIAL AND METHODS: The cohort was classified into two groups: a study group, consisting of 56 individuals diagnosed with premature ovarian insufficiency (and who were younger than 40 years of age, had an antral follicle count <3-5, and FSH levels >12 IU/I), and a control group, consisting of 45 fertile individuals. A total of 101 individuals were analyzed by next-generation sequencing to detect BRCA1 and BRCA2 gene mutations. RESULTS: We detected four new variations (p.T1246N and p.R1835Q in BRCA1 and p.I3312V and IVS-7T>A in BRCA2) that had not been reported before. CONCLUSION: We did not find an association between the BRCA1 and BRCA2 gene mutations and premature ovarian insufficiency. However, larger, functional studies are needed to clarify the association. PMID- 27403074 TI - Effect of body mass index and age on in vitro fertilization in polycystic ovary syndrome. AB - OBJECTIVE: The aim of this study was to investigate age-related variations in the effect of body mass index (BMI) on in vitro fertilization (IVF) outcomes. MATERIAL AND METHODS: This was a cohort study conducted by retrospectively investigating the IVF cycles of 653 polycystic ovary syndrome (PCOS) patients under the age of 40 years who were diagnosed based on the Rotterdam criteria in a private IVF clinic between 2005 and 2015. The study included data from 653 IVF cycles of PCOS patients. The patients were classified into three groups based on their BMI, i.e., normal weight (n=299), overweight (n=208), and obese (n=146). The patients were also grouped by age: 562 patients were under the age of 35 years and 91 patients were above the age of 35 years. Then, BMI- and age-related variations in the IVF cycle parameters and clinical pregnancy rates of patients with PCOS were investigated. The Mantel-Haenszel Chi-square statistical assessment method was used to determine whether the effect of BMI on IVF outcomes varies with age. RESULTS: Variations in cycle variables with BMI and age showed that IVF cycles were negatively affected by increases in obesity and age. Clinical pregnancy rates were found to be lower in the obese group than in the other groups, particularly in the age group above 35 years; however, this difference could not be proven statistically. CONCLUSION: The present study evaluated obesity and clinical pregnancy rates in IVF cycles in PCOS patients according to age groups, and particularly in the obese group, the clinical pregnancy rates were observed to be lower in the age group >=35 years than in the other BMI groups; however, this difference was found to be statistically insignificant. PMID- 27403075 TI - PGD management scheme for older females with balanced translocations: Do older females have less chance of balanced embryo transfer? AB - OBJECTIVE: Carriers of reciprocal and Robertsonian translocations have a higher risk of experiencing infertility and repeated miscarriages. It is well established that with advancing maternal age, the risk of aneuploidies in embryos increases. In this study, the chance of developing balanced embryos in translocation carriers with advanced maternal age was analyzed to establish a management scheme for couples seeking fertility treatment and preimplantation genetic diagnosis (PGD). MATERIAL AND METHODS: Biopsy was performed on cleavage stage embryos. Multicolor fluorescence in situ hybridization was used for PGD. The translocation carriers underwent a total of 55 cycles of PGD. Genetics diagnosis and cycle outcomes of PGD cases were examined. RESULTS: This study showed that the chance of obtaining a balanced embryo from the Robertsonian translocation carriers was significantly less when the maternal age is advanced. Similar rates for balanced embryos were obtained from the reciprocal translocation carriers. CONCLUSION: The results of this study show that maternal age plays an important role and that genetic counselling and planning for a PGD cycle in translocation carriers, particularly for Robertsonian carriers, must be accordingly adapted. PMID- 27403076 TI - Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center. AB - OBJECTIVE: To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). MATERIAL AND METHODS: Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. RESULTS: A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1-809 IU/mL). Median tumor size was 200 mm (range, 40-400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. CONCLUSION: Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID- 27403077 TI - Evaluation of vaginal agenesis treated with the modified McIndoe technique: A retrospective study. AB - OBJECTIVE: Retrospective analysis of cases that have undergone neovagina operation because of congenital vaginal agenesis was objected. MATERIAL AND METHODS: Seven cases applying with the complaints of primary amenorrhea or inability to have sexual intercourse were in the study. The cases were diagnosed with congenital vaginal agenesis and operated at Mustafa Kemal University Training and Research Hospital between 2011 and 2014. Vaginoplasty by the modified McIndoe method was performed in all cases. The main complaint, chromosomal analysis, duration of operation, preoperative and postoperative vaginal length, complications, postoperative treatment, and satisfaction from the sexual intercourse were all evaluated. RESULTS: Average age of our patients was 28.14+/-8.61 (19-39) years. One patient was 46XX-45X0 mosaic Turner syndrome), 1 patient was 46XY (testicular feminization), and other 5 patients were 46XX. The average duration of operation was 2.7+/-0.56 (2-3.5 h). Postoperative infection was observed in 1 patient. In this infected patient, graft failure occurred and debridement was performed in reoperation. No early complications were seen in the others. Preoperative and postoperative average vaginal lengths were 1.85+/-0.62 (1-3 cm) and 8.71+/-1.11 (7-10 cm), respectively. Dyspareunia occurred in 2 cases that were not able to use dilatator regularly: 1 because of cancelation of marriage and the other because of postoperative infection; regular sexual life was achieved in remaining 5 (71%) cases. CONCLUSION: Although there is no consensus about the ideal method of making a functioning vagina among different specialties. The modified McIndoe technique is the most applied method by gynecologists and simple, minimally invasive and with low morbidity. PMID- 27403078 TI - Application of da Vinci((r)) Robot in simple or radical hysterectomy: Tips and tricks. AB - The first robotic simple hysterectomy was performed more than 10 years ago. These days, robotic-assisted hysterectomy is accepted as an alternative surgical approach and is applied both in benign and malignant surgical entities. The two important points that should be taken into account to optimize postoperative outcomes in the early period of a surgeon's training are how to achieve optimal oncological and functional results. Overcoming any technical challenge, as with any innovative surgical method, leads to an improved surgical operation timewise as well as for patients' safety. The standardization of the technique and recognition of critical anatomical landmarks are essential for optimal oncological and clinical outcomes on both simple and radical robotic-assisted hysterectomy. Based on our experience, our intention is to present user-friendly tips and tricks to optimize the application of a da Vinci(r) robot in simple or radical hysterectomies. PMID- 27403079 TI - Three-dimensional ultrasonography by means of HDlive rendering in the first trimester of pregnancy: A pictorial review. AB - Our objective was to describe early embryo/fetus anatomy and abnormalities provided by three and four-dimensional (3D/4D) ultrasound using HDlive rendering technology in the first trimester of pregnancy. Normal and pathologic embryonic and fetal volume data set with postprocessing using HDlive rendering mode. Virtual fetoscopic imaging of the normal and pathologic fetus even at early stage of development with increasing maternal-fetal bonding process. HDlive represents a novel and valuable lightening system for 3D/4D ultrasound application that may aid the prenatal interpretation of early congenital malformations although limitations and cautions are still needed for inclusion in obstetric clinical practice. PMID- 27403080 TI - Pessary use in pregnant women with short cervix. AB - The purpose of this case series is to provide preliminary evidence on the efficacy of pessary application in women with short cervix and at risk for preterm labor. Between May 2015 and July 2015, four pregnant women were followed up with Arabin pessaries. The gestational age at the time of diagnosis was between the 23(th) and 29(th) weeks. Pessary application was associated with a prolongation of pregnancy lasting between 28 and 98 days. The gestational age at the time of delivery was between the 33rd and 39th weeks. Pessary use is non invasive for the prolongation of pregnancy in pregnant women with shortened cervix. The major advantage of pessary use is its easy application without requiring anesthesia. PMID- 27403081 TI - What is your diagnosis? PMID- 27403082 TI - A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas. AB - Background. Belinostat is a novel histone deacetylase inhibitor. Primary Objectives. Maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of belinostat (Bel) in combination with doxorubicin (Dox) in solid tumours (phase I) and response rate (RR) in soft tissue sarcomas (phase II). Methods. Bel was administered as a 30-minute IV infusion on days 1-5 and on day 5 with Dox. The dose escalation schedule was as follows: cohort 1: Bel 600 mg/m(2) and 50 mg/m(2) Dox, cohort 2: Bel 600 mg/m(2) and 75 mg/m(2) Dox, cohort 3: Bel 800 mg/m(2) and 75 mg/m(2) Dox, and cohort 4: Bel 1000 mg/m(2) and 75 mg/m(2) Dox. Results. 41 patients were included (25 in phase I, 16 in phase II). Adverse events were fatigue (95%), nausea (76%), and alopecia (63%). There was one DLT, grade 3 rash/hand and foot syndrome. MTD was Bel 1000 mg/m(2)/d and Dox 75 mg/m(2). Four responses were seen: 2 PR in phase I, RR of 8%; in phase II, 1 PR/1 CR, RR of 13%, and 9 patients (56%) with SD. Conclusion. The combination was well tolerated. Response rate was moderate but median time to progression was 6.0 months (95% CI, 1.6-9.7 months) which is superior to some reports of single-agent Dox. PMID- 27403083 TI - Sources of salinity and arsenic in groundwater in southwest Bangladesh. AB - BACKGROUND: High salinity and arsenic (As) concentrations in groundwater are widespread problems in the tidal deltaplain of southwest Bangladesh. To identify the sources of dissolved salts and As, groundwater samples from the regional shallow Holocene aquifer were collected from tubewells during the dry (May) and wet (October) seasons in 2012-2013. Thirteen drill cores were logged and 27 radiocarbon ages measured on wood fragments to characterize subsurface stratigraphy. RESULTS: Drill cuttings, exposures in pits and regional studies reveal a >5 m thick surface mud cap overlying a ~30 m thick upper unit of interbedded mud and fine sand layers, and a coarser lower unit up to 60 m thick dominated by clean sands, all with significant horizontal variation in bed continuity and thickness. This thick lower unit accreted at rates of ~2 cm/year through the early Holocene, with local subsidence or compaction rates of 1-3 mm/year. Most tubewells are screened at depths of 15-52 m in sediments deposited 8000-9000 YBP. Compositions of groundwater samples from tubewells show high spatial variability, suggesting limited mixing and low and spatially variable recharge rates and flow velocities. Groundwaters are Na-Cl type and predominantly sulfate-reducing, with specific conductivity (SpC) from 3 to 29 mS/cm, high dissolved organic carbon (DOC) 11-57 mg/L and As 2-258 ug/L, and low sulfur (S) 2 33 mg/L. CONCLUSIONS: Groundwater compositions can be explained by burial of tidal channel water and subsequent reaction with dissolved organic matter, resulting in anoxia, hydrous ferric oxide (HFO) reduction, As mobilization, and sulfate (SO4) reduction and removal in the shallow aquifer. Introduction of labile organic carbon in the wet season as rice paddy fertilizer may also cause HFO reduction and As mobilization. Variable modern recharge occurred in areas where the clay cap pinches out or is breached by tidal channels, which would explain previously measured (14)C groundwater ages being less than depositional ages. Of samples collected from the shallow aquifer, Bangladesh Government guidelines are exceeded in 46 % for As and 100 % for salinity. PMID- 27403084 TI - An Optimized Protocol for Packaging Pseudotyped Integrase Defective Lentivirus. AB - BACKGROUND: A number of integrase defective lentiviral (IDLV) packaging systems have been developed to produce integration deficient lentiviruses for gene delivery and epichromosomal expression. However, despite their growing demand, a comparative study to systemically evaluate the performance efficiency of different mutants on virus packaging and gene expression has not been done. RESULTS: Site-directed mutagenesis was used to generate five integrasedeficient mutants for non-integrative lentiviral packaging (NILVP). The five mutants were then individually incorporated to make different integrase defective lentivirus plasmid packaging mix, keeping other packaging factors constant. CD511B-1, a lentivectorexpressing GFP from an EF1 promoter, was packaged with each of the five different lentivirus packaging mix to make pseudotypedviral particles. The performance and packaging efficiency of each of the integrase deficient mutants was evaluated based on GFP expression in HT1080 cells, while the wild type lentivirus packaging mix was used as a control. Of the five integrase mutant candidates, one with the highestGFP transgene expression level was chosen for further characterization. The non-integrative nature of this candidate was confirmed by quantitative polymerase chain reaction and characterized using both dividing and non-dividing cells. Finally, a detailed standard protocol for NILVP using this integrase defective mutant was developed. CONCLUSIONS: An efficient lentiviral packaging system for producing on-integrative lentivirus was established. This system is compatible with most existing lentivectors and can be used to transduce both dividing and non-dividing cells. PMID- 27403085 TI - CELL TRACKING USING PARTICLE FILTERS WITH IMPLICIT CONVEX SHAPE MODEL IN 4D CONFOCAL MICROSCOPY IMAGES. AB - Bayesian frameworks are commonly used in tracking algorithms. An important example is the particle filter, where a stochastic motion model describes the evolution of the state, and the observation model relates the noisy measurements to the state. Particle filters have been used to track the lineage of cells. Propagating the shape model of the cell through the particle filter is beneficial for tracking. We approximate arbitrary shapes of cells with a novel implicit convex function. The importance sampling step of the particle filter is defined using the cost associated with fitting our implicit convex shape model to the observations. Our technique is capable of tracking the lineage of cells for nonmitotic stages. We validate our algorithm by tracking the lineage of retinal and lens cells in zebrafish embryos. PMID- 27403086 TI - New Diagnostic Strategies in Infection Safety: The (R)evolution? PMID- 27403088 TI - Selective Testing of At-Risk Blood Donors for Trypanosoma cruzi and Plasmodium spp. in Switzerland. AB - BACKGROUND: Population migrations and overseas recreational travel to regions at risk for tropical diseases are increasing. A major challenge in non-endemic countries is to decrease the number of blood donor deferrals due those tropical disease pathogens, without compromising the high level of blood safety. The protozoans Trypanosoma cruzi and Plasmodium spp., the causative organisms of Chagas disease (CD) and malaria are becoming a major focus in the blood transfusion community. METHODS: National guidelines of the Blood Transfusion Service of the Swiss Red Cross propose an algorithm for dealing with these pathogens, including a mandatory selective serological testing of donors at risk. RESULTS: 6,978 donors at risk for CD were tested. Three of them were confirmed anti-T. cruzi -positive, and in one case a transfusion-transmitted infection was highly possible. The specificity of the assay was 99.94%. For malaria 12,887 donors were at risk and 178 were confirmed positive. The specificity of the assays was 92.8%. CONCLUSION: CD and malaria in non-endemic countries may represent a certain risk for blood transfusion. Switzerland chose a selective testing approach. The specificity of the assays is a crucial topic for this approach because it ensures a minimal loss of false-reactive donors and helps towards an easier counselling of implicated donors. PMID- 27403087 TI - West Nile Virus in Europe and Safety of Blood Transfusion. AB - West Nile virus (WNV) has become an increasing issue in the transfusion setting since 2002, when it was firstly shown in the USA that it can be transmitted through blood transfusion. Since then, several precautionary measures have been introduced in Europe in order to reduce the possible risk of transmission via transfusion/solid organ transplantation. In addition, the epidemiological surveillance has been tightened and the network for communication of human WNV cases strengthened. This review will focus on WNV circulation and the safety of blood in Europe. PMID- 27403089 TI - Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for Individual NAT Screening of Blood, Hematopoietic Stem Cell, Tissue and Organ Donors. AB - BACKGROUND: The performance of the multiplex Procleix Ultrio Elite assay as individual donor nucleic acid test (ID-NAT) for the detection of HIV-1, HIV-2, HCV, and HBV was evaluated in a retrospective, single center study. METHODS: ID NAT results of 21,181 blood donors, 984 tissue donors, 293 hematopoietic stem cell donors and 4 organ donors were reviewed in synopsis with results of serological screening and additional discriminatory and repetitive NAT in case of positive donors. RESULTS: Specificity of the initial Procleix Ultrio Elite assay was 99.98% and after discriminatory testing 100.00%. Initially invalid results were observed in 75 of 21,181 blood donors (0.35%) but 16 of 984 tissue donors (1.62%, p < 0.001) which included non-heart-beating ('cadaveric') donors. All these had valid negative ID-NAT results after repeated testing or testing of 1:5 diluted specimens in case of tissue donors. Occult hepatitis B (defined here as HBV DNAemia without HBsAg detection) was demonstrated by ID-NAT in two anti-HBc positive tissue donors and suspected in two other tissue donors, where a definite diagnosis was not achieved due to the insufficient sample volumes available. CONCLUSION: The Procleix Ultrio Elite assay proved to be specific, robust and rapid. Therefore, routine ID-NAT may also be feasible for organ and granulocyte donors. PMID- 27403090 TI - Implementation of an HIV-1 Triple-Target NAT Assay in the Routine Screening at Three German Red Cross Blood Centres. AB - BACKGROUND: Blood product safety was significantly improved by the introduction of NAT testing in the late 1990s, resulting in a strong decrease of transfusion transmitted infections (TTIs). Due to the occurrence of HIV-1 NAT test failures as a consequence of mismatch mutations in the amplicon regions of mono-target NAT assays, the Paul Ehrlich Institute mandated the implementation of multi-target NAT assays for HIV-1 in 2014. Commercial suppliers mostly developed dual-target NAT assays, with only one implementing a triple-target NAT assay. METHODS: The HIV-1 triple-target NAT assay v3 (GFE Blut) was tested on mutated specimens and synthetic DNA bearing mutations that resulted in sample underquantification or false-negative test results. In addition, data from 2 years routine testing at three German Red Cross Blood centres were analysed. RESULTS: The HIV-1 triple target PCR could compensate for all mutations tested and could compensate the loss of one amplicon without a significant loss of sensitivity. Data from 2 years routine testing showed a solid performance. CONCLUSION: The HIV-1 triple-target v3 assay (GFE Blut) can compensate mutations in target sequences better than a dual-target assay and is applicable to high-throughput screening, thus increasing blood product safety. PMID- 27403091 TI - In vitro Quality of Platelets with Low Plasma Carryover Treated with Ultraviolet C Light for Pathogen Inactivation. AB - BACKGROUND: The THERAFLEX UV-Platelets system uses shortwave ultraviolet C light (UVC, 254 nm) to inactivate pathogens in platelet components. Plasma carryover influences pathogen inactivation and platelet quality following treatment. The plasma carryover in the standard platelets produced by our institution are below the intended specification (<30%). METHODS: A pool and split study was carried out comparing untreated and UVC-treated platelets with <30% plasma carryover (n = 10 pairs). This data was compared to components that met specifications (>30% plasma). The platelets were tested over storage for in vitro quality. RESULTS: Platelet metabolism was accelerated following UVC treatment, as demonstrated by increased glucose consumption and lactate production. UVC treatment caused increased externalization of phosphatidylserine on platelets and microparticles, activation of the GPIIb/IIIa receptor (PAC-1 binding), and reduced hypotonic shock response. Platelet function, as measured with thrombelastogram, was not affected by UVC treatment. Components with <30% plasma were similar to those meeting specification with the exception of enhanced glycolytic metabolism. CONCLUSION: This in vitro analysis demonstrates that treatment of platelets with <30% plasma carryover with the THERAFLEX UV-Platelets system affects some aspects of platelet metabolism and activation, although in vitro platelet function was not negatively impacted. This study also provides evidence that the treatment specifications of plasma carryover could be extended to below 30%. PMID- 27403092 TI - Parvovirus B19 Passive Transmission by Transfusion of Intercept(r) Blood System Treated Platelet Concentrate. AB - BACKGROUND: Pathogen reduction methods for blood components are effective for a large number of viruses though less against small, non-enveloped viruses such as Parvovirus B19 (B19V). This article describes the passive transmission by transfusion of two B19V-contaminated pooled platelet concentrates (PCs) which were treated with the Intercept(r) blood pathogen reduction system. CASE REPORTS: Two transfusion cases of B19V-contaminated Intercept-treated pooled PCs were described. Due to the analysis delay, the PCs were already transfused. The viral content of each donation was 4.87 * 10(10) IU/ml in case 1and 1.46 * 10(8) IU/ml in case 2. B19V (52 IU/ml) was detected in the recipient of the case 1 PC, whereas no virus could be detected in the case 2 PC recipient. A B19V IgM response and a transient boost of the underlying B19V IgG immune status and was observed in recipient 1. Recipient of the case 2 PC remained B19V IgG- and IgM negative. B19V DNA sequence and phylogenetic analysis revealed a 100% homology between donor and recipient. CONCLUSION: This report describes passive B19V transmission by a PC with very high B19 viral load which elicited a transient boost of the B19V immunity, but not by a PC with a lower B19V content, suggesting that there is a B19 viral load threshold value at which B19V inactivation is exceeded. PMID- 27403095 TI - Intrathoracic Hernia after Total Gastrectomy. AB - Intrathoracic hernias after total gastrectomy are rare. We report the case of a 78-year-old man who underwent total gastrectomy with antecolic Roux-Y reconstruction for residual gastric cancer. He had alcoholic liver cirrhosis and received radical laparoscopic proximal gastrectomy for gastric cancer 3 years ago. Early gastric cancer in the remnant stomach was found by routine upper gastrointestinal endoscopy. We initially performed endoscopic submucosal dissection, but the vertical margin was positive in a pathological result. We performed total gastrectomy with antecolic Roux-Y reconstruction by laparotomy. For adhesion of the esophageal hiatus, the left chest was connected with the abdominal cavity. A pleural defect was not repaired. Two days after the operation, the patient was suspected of having intrathoracic hernia by chest X rays. Computed tomography showed that the transverse colon and Roux limb were incarcerated in the left thoracic cavity. He was diagnosed with intrathoracic hernia, and emergency reduction and repair were performed. Operative findings showed that the Roux limb and transverse colon were incarcerated in the thoracic cavity. After reduction, the orifice of the hernia was closed by suturing the crus of the diaphragm with the ligament of the jejunum and omentum. After the second operation, he experienced anastomotic leakage and left pyothorax. Anastomotic leakage was improved with conservative therapy and he was discharged 76 days after the second operation. PMID- 27403093 TI - Human Immunodeficiency Virus (HIV). PMID- 27403094 TI - Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives: Chapter 5 Human Albumin - Revised. AB - Chapter 5 'Human Albumin' that was suspended on January 10, 2011 has been completed and updated in the present version. PMID- 27403096 TI - Spread of Intraductal Papillary Neoplasm Arising from the Cystic Duct of the Biliary Tree. AB - Intraductal papillary neoplasm of the bile duct (IPNB) is a variant type of the bile duct carcinoma characterized by intraductal growth. IPNB is also recognized as a precursor of invasive carcinoma. We describe herein an extremely rare case of IPNB arising from the cystic duct. A 68-year-old man was admitted to our hospital for investigation of epigastralgia and abnormal levels of biliary tract enzyme. Computed tomography and magnetic resonance imaging showed a mass lesion spreading from the cystic duct to the upper-middle bile duct. Endoscopic retrograde cholangiography demonstrated diffuse duct dilation with a grossly visible intraductal mass and amorphous blobs, suggesting the presence of mucobilia or scattered tumors. We performed extrahepatic bile duct resection with lymphadenectomy. Macroscopically, a friable papillary tumor originated from the cystic duct grows intraluminally into the bile duct. Pathologically, the tumor was found to be intramucosal adenocarcinoma spreading to the whole extrahepatic bile duct, which was compatible with IPNB. We should discuss the features and progression processes of IPNB through this precious case. PMID- 27403097 TI - Safety of Regular-Dose Imatinib Therapy in Patients with Gastrointestinal Stromal Tumors Undergoing Dialysis. AB - The number of cancer patients undergoing dialysis has been increasing, and the number of these patients on chemotherapy is also increasing. Imatinib is an effective and safe therapy for KIT-positive gastrointestinal stromal tumors (GIST), but the efficacy and safety of imatinib in dialysis patients remain unclear. Because clinical trials have not been conducted in this population, more investigations are required. We report on a 75-year-old Japanese man undergoing dialysis who presented with massive tarry stool from a duodenal GIST. The duodenal GIST was 14 cm in diameter with multiple liver and bone metastases. The patient underwent an urgent pancreaticoduodenectomy to achieve hemostasis. After surgery, he was administered imatinib 400 mg/day. No severe adverse event including myelosuppression, congestive heart failure, liver functional impairment, intestinal pneumonia, or Steven-Johnson syndrome occurred, and the liver metastasis remained stable for 4 months. During chemotherapy, hemodialysis continued three times per week without adverse events. We suggest that regular dose imatinib is an effective and safe treatment in patients with GIST undergoing dialysis. In addition, we present a literature review of the effectiveness and safety of imatinib treatment in dialysis patients. PMID- 27403098 TI - Appendiceal Adenocarcinoma Presenting as a Rectal Polyp. AB - Appendiceal adenocarcinoma typically presents as an incidentally noted appendiceal mass, or with symptoms of right lower quadrant pain that can mimic appendicitis, but local involvement of adjacent organs is uncommon, particularly as the presenting sign. We report on a case of a primary appendiceal cancer initially diagnosed as a rectal polyp based on its appearance in the rectal lumen. The management of the patient was in keeping with standard practice for a rectal polyp, and the diagnosis of appendiceal adenocarcinoma was made intraoperatively. The operative strategy had to be adjusted due to this unexpected finding. Although there are published cases of appendiceal adenocarcinoma inducing intussusception and thus mimicking a cecal polyp, there are no reports in the literature describing invasion of the appendix through the rectal wall and thus mimicking a rectal polyp. The patient is a 75-year-old female who presented with spontaneous hematochezia and, on colonoscopy, was noted to have a rectal polyp that appeared to be located within a diverticulum. When endoscopic mucosal resection was not successful, she was referred to colorectal surgery for a low anterior resection. Preoperative imaging was notable for an enlarged appendix adjacent to the rectum. Intraoperatively, the appendix was found to be densely adherent to the right lateral rectal wall. An en bloc resection of the distal sigmoid colon, proximal rectum and appendix was performed, with pathology demonstrating appendiceal adenocarcinoma that invaded through the rectal wall. The prognosis in this type of malignancy weighs heavily on whether or not perforation and spread throughout the peritoneal cavity have occurred. In this unusual presentation, an en bloc resection is required for a complete resection and to minimize the risk of peritoneal spread. Unusual appearing polyps do not always originate from the bowel wall. Abnormal radiographic findings adjacent to an area of gastrointestinal pathology may signify locally advanced disease from a surrounding organ that secondarily involves the gastrointestinal tract. These findings warrant further investigation prior to any intervention to ensure appropriate treatment. PMID- 27403099 TI - Intestinal Anisakiasis Treated Successfully with Prednisolone and Olopatadine Hydrochloride. AB - The clinical characteristic of gastrointestinal anisakiasis is severe abdominal pain after eating raw fish. Intestinal anisakiasis is more uncommon than gastric anisakiasis. Most patients with intestinal anisakiasis need hospitalization because anisakiasis can cause intestinal obstruction, ileus, peritonitis or intestinal perforation. We report a case of intestinal anisakiasis. A 43-year-old woman presented with symptoms of intermittent abdominal pain 2 days after eating raw fish. Her brother had eaten the same food and had been suffering from gastric anisakiasis. Abdominal ultrasonography in this patient showed localized jejunal wall thickening with dilated lumen of proximal jejunum and ascites. According to the clinical course and examinations, she was diagnosed with intestinal anisakiasis. Administration of prednisolone 5 mg/day and olopatadine hydrochloride 10 mg/day improved her symptoms quickly without hospitalization. Prednisolone was administered for 10 days, and olopatadine hydrochloride was administered for a total of 6 weeks according to ultrasonographic findings. Six months after the treatment, the abdominal ultrasonography demonstrated normal findings. This case demonstrates that ultrasonography was quite useful for the diagnosis and surveillance of intestinal anisakiasis. Furthermore, treatment with corticosteroid and an antiallergic agent could be an option for patients with intestinal anisakiasis. PMID- 27403100 TI - Acute Cytomegalovirus Hepatitis in an Immunocompetent Host as a Reason for Upper Right Abdominal Pain. AB - Cytomegalovirus infections are widely distributed with a seroprevalence of up to 100%. The majority of the cases take a silent course or deal with unspecific clinical symptoms. Complications in immunocompetent patients are rare but may affect the liver and lead up to an acute organ failure. In this case report, we describe a 35-year-old immunocompetent female with an acute cytomegalovirus infection presenting as acute hepatitis with ongoing upper right abdominal pain after cholecystectomy. Upper right abdominal pain is a common symptom with a wide range of differential diagnoses. If common reasons can be excluded, we want to sensitize for cytomegalovirus infection as a minor differential diagnosis even in immunocompetent patients. PMID- 27403101 TI - Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology. AB - Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID- 27403102 TI - Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine. AB - Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID- 27403104 TI - Sclerosing Mesenteritis: A Rare Cause of Small Bowel Obstruction. AB - Sclerosing mesenteritis falls within a spectrum of primary idiopathic inflammatory and fibrotic processes that affect the mesentery. The exact etiology has not been determined, although the following associations have been noted: abdominal surgery, trauma, autoimmunity, paraneoplastic syndrome, ischemia and infection. Progression of sclerosing mesentritis can lead to bowel obstruction, a rare complication of this uncommon condition. We report a case of a 66-year-old female with abdominal pain who was noted to have a small bowel obstruction requiring laparotomy and a partial small bowel resection. The pathology of the resected tissue was consistent with sclerosing mesenteritis, a rare cause of a small bowel obstruction. Sclerosing mesenteritis has variable rates of progression, and there is no consensus regarding the optimal treatment. Physicians should consider sclerosing mesenteritis in the differential diagnosis of a small bowel obstruction. PMID- 27403103 TI - Usefulness Of Three-Dimensional Printing Models for Patients with Stoma Construction. AB - The use of patient-specific organ models in three-dimensional printing systems could be helpful for the education of patients and medical students. The aim of this study was to clarify whether the use of patient-specific stoma models is helpful for patient education. From January 2014 to September 2014, 5 patients who underwent colorectal surgery and for whom a temporary or permanent stoma had been created were involved in this study. Three-dimensional stoma models and three-dimensional face plates were created. The patients' ages ranged from 59 to 81 years. Four patients underwent stoma construction because of rectal cancer, and 1 underwent stoma construction because of colon stenosis secondary to recurrent cancer. All patients were educated about their stoma and potential stoma-associated problems using three-dimensional stoma models, and all practiced cutting face plates using three-dimensional face plates. The models were also used during medical staff conferences to discuss current issues. All patients understood their problems and finally became self-reliant. The recent availability of three-dimensional printers has enabled the creation of many organ models, and full-scale stoma and face plate models are now available for patient education on cutting an appropriately individualized face plate. Thus, three dimensional printers could enable fewer skin problems than are currently associated with daily stomal care. PMID- 27403105 TI - A Delayed Diagnosis of Chronic Mesenteric Ischaemia: The Role of Clinicians' Cognitive Errors. AB - Chronic diarrhoeal illnesses with nausea and weight loss are a common indication for gastroenterology review. While many such cases have intra-luminal aetiologies, such as inflammatory bowel disease, coeliac disease or other malabsorptive conditions, with many other cases due to functional gut disorders or systemic malignancy, clinicians must also keep vascular disorders in mind. Here we report a patient with a delayed diagnosis of chronic mesenteric ischaemia after 6 months of gastrointestinal symptoms strongly mimicking an alternative diagnosis such as inflammatory bowel disease due an atypical predominance of nausea and diarrhoea rather than pain. We briefly review the literature on treatment of this condition but also discuss with particular attention the sequence of cognitive errors made by clinicians that led to a diagnostic delay, inviting readers to thus reflect on how such errors can be minimised in their practice. PMID- 27403106 TI - Hematogenous Gastric Metastasis of Pancreatic Cancer. AB - While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2 cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas. PMID- 27403107 TI - Gastrointestinal Zygomycosis Masquerading as Acute Appendicitis. AB - Zygomycosis is a rare invasive opportunistic fungal infection that occurs in the setting of hematologic malignancies, chemotherapy-induced neutropenia, and immunosuppressive therapies. We report the first case of disseminated appendiceal zygomycosis due to Absidia spp. in a neutropenic patient who initially presented as acute appendicitis. A 63-year-old woman with acute myeloid leukemia presented as acute appendicitis while receiving induction chemotherapy and ultimately succumbed to overwhelming disseminated zygomycosis. Initial symptoms included loose stools and right lower abdominal pain unresponsive to broad-spectrum antibiotics. Clinical examination and cross-sectional imaging suggested acute appendicitis. The final diagnosis was established by histological evaluations of the ileocecectomy specimen, which showed angioinvasive fungal organisms within the necrotic appendiceal wall with characteristics typical of zygomycetes. Fungal cultures demonstrated Absidia spp. The patient was treated with amphotericin B but expired in the setting of fungal sepsis. A diagnosis of a fungal infection, including zygomycosis, should be considered in all chemotherapy-induced neutropenic patients who present with symptoms of acute appendicitis. A high index of clinical suspicion with prompt histologic and culture diagnosis of zygomycosis may reduce the high mortality and morbidity associated with zygomycosis of the gastrointestinal tract. PMID- 27403108 TI - Two Cases of Paradoxical Hidradenitis Suppurativa while on Adalimumab. AB - Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by recurring abscesses, nodules, and fistulas predominantly in the groin and axillae. The association between HS and Crohn's disease (CD) has been well documented. Tumor necrosis factor (TNF) inhibitors have shown to be effective in treating both HS and CD. We report 2 patients who developed HS while on TNF inhibitor treatment for CD. PMID- 27403109 TI - Idiopathic Adulthood Ductopenia: 'It Is Out There'. AB - Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic entity of unknown origin characterized by loss of inter-lobular bile ducts that was first described two decades ago. Although the diagnostic criteria have been described in detail, IAD continues to be a rare diagnosis. Our thorough literature search revealed less than a hundred cases of IAD reported. Here we present a 34-year-old female with no significant past history who was evaluated for persistent elevation of serum alkaline phosphate levels. Serology was negative for all viral hepatitides, and a chronic liver disease workup was unremarkable. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography did not reveal any abnormalities in the biliary tree. Finally, a liver biopsy demonstrated ductopenia involving greater than 50% of the portal triads, making a diagnosis of IAD. Since the disease can progress rapidly, close follow-up is warranted, so liver transplantation can be pursued if deemed necessary. PMID- 27403110 TI - Clinical Evaluation of Hepatic Portal Venous Gas after Abdominal Surgery. AB - Hepatic portal venous gas (HPVG) is induced by various abdominal diseases. Since HPVG is accompanied by bowel ischemia, intestinal infection and hypovolemia, various modes of critical management are needed to treat the underlying conditions. HPVG associated with abdominal complications after surgery has rarely been reported. We present 4 patients with HPVG after abdominal surgery: 2 of the 4 patients died of multiple organ failure, and the other 2 recovered with solely conservative therapy. Although postoperative HPVG is a severe and life threatening condition, early detection and systemic treatment lead to a better patient outcome. PMID- 27403111 TI - Orbital Pseudotumor as a Rare Extrahepatic Manifestation of Hepatitis C Infection. AB - Hepatitis C is frequently accompanied by immune-related extrahepatic manifestations affecting the skin, kidneys, central and peripheral nervous system and exocrine glands. We present the case of a 40-year-old man with left-sided ptosis, exophthalmos and headache. MRI demonstrated left-sided orbital pseudotumor with lacrimal and retro-orbital contrast enhancement extending to the cavernous sinus and the vestibulocochlear nerve. Immunological tests of serum and cerebrospinal fluid identified hepatitis C virus (HCV) as a potential causative agent but did not indicate any additional infectious, malignant or immunological disorder. Hepatological evaluation revealed no signs of advanced liver disease. After initial spontaneous improvement, the patient subsequently developed vestibulocochlear failure with gait disorder, tinnitus and transient left parietal sensory loss. Lacrimal biopsy demonstrated lymphocytic infiltrate, prompting steroid treatment. After initial improvement, steroids could not be tapered below 40 mg daily for several months due to recurrent symptoms. Twelve months after the initial presentation, the patient's chronic HCV infection was successfully treated with sofosbuvir, simeprevir and ribavirin and he remains now free of symptoms without steroids. In patients with chronic hepatitis C, lymphocytic infiltrate of the salivary and lacrimal glands is a frequent phenomenon. However, the extent of the lymphocytic infiltrate beyond the lacrimal gland to the tip of the orbit, cavernous sinus and vestibulocochlear nerve as in our patient is highly unusual. For all symptomatic extrahepatic manifestations of hepatitis C infection, treatment of HCV as the underlying immune stimulus is recommended, and it helped to control the symptoms in our patient. In addition, long-term follow-up for recurrent lymphocyte infiltrate and development of lymphoma is warranted. PMID- 27403112 TI - Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis. AB - Benign cystic mesothelioma (BCM) is a rare benign disease that forms multicystic masses in the abdomen, pelvis, and retroperitoneum. It occurs predominantly in young to middle-aged women. The majority of cases were associated with a history of abdominal or pelvic operation, a history of endometriosis, and pelvic inflammatory disease. We present a unique case of BCM which is different to the previous cases. The patient was a 52-year-old man showing features of peritoneal carcinomatosis accompanied by ascites on abdominal computed tomography scans. We herein report a case of BCM misdiagnosed with peritoneal carcinomatosis. PMID- 27403113 TI - Gastric Perforation by Ingested Rabbit Bone Fragment. AB - The majority of accidentally ingested foreign bodies is excreted from the gastrointestinal (GI) tract without any complications. Sometimes sharp foreign bodies - like chicken and fish bones - can lead to intestinal perforation and may present insidiously with a wide range of symptoms and, consequently, different diagnoses. We report the case of a 59-year-old woman presenting with fever and a 1-month history of vague abdominal pain. Computed tomography (CT) showed the presence of a hyperdense linear image close to the gastric antrum surrounded by a fluid collection and free peritoneal air. At laparotomy, a 4-cm rabbit bone fragment covered in inflamed tissue was detected next to a gastric wall perforation. Rabbit bone fragment ingestion, even if rarely reported, should not be underestimated as a possible cause of GI tract perforation. PMID- 27403114 TI - Self-Expanding Metal Stenting in the Management of a Benign Colonic Stricture. AB - Colonic postanastomotic strictures occur in 1.5-8% of patients following colorectal surgery. Traditionally, colonic strictures were treated by multiple modalities including endoscopic dilatation. Self-expanding metal stents (SEMS) have been indicated in the management of benign colonic strictures; however, there are limited available data with regard to their efficacy. We present the case of a 68-year-old male who had perforated sigmoid diverticulitis followed by Hartmann's procedure with eventual reanastomosis 6 months later. He subsequently developed benign colonic stricture, which was treated with a metal stent. SEMS are associated with a low mortality rate and are appropriate in treating acute colonic obstruction as a result of benign stricture in the setting of postanastomosis. PMID- 27403115 TI - A Very Rare Cause of a Relapsing Para-Oesophageal Abscess. AB - Oesophageal involvement in Crohn's disease (CD) is uncommon and most often accompanied by involvement of more distal parts. Its presentation is mostly non specific, and therefore a diagnosis, especially in isolated oesophageal disease, is difficult. We present the case of a 42-year-old male patient who was referred to our gastroenterology department because of a para-oesophageal abscess. Under antibiotic treatment the abscess healed, but despite great diagnostic efforts, its aetiology remained unclear. Three years later the patient was hospitalized again because of an abscess at the same site. Endoscopy showed disseminated ulcerations of the lower oesophagus, raising suspicion of CD. After excluding other possible causes, we made the diagnosis of isolated CD of the oesophagus. We review the available literature on this topic and discuss the clinical presentation, symptoms, endoscopic findings, and histology as well as treatment of oesophageal CD. PMID- 27403117 TI - Jaw Dislocation as an Unusual Complication of Upper Endoscopy. AB - This case report presents an unusual complication of upper endoscopy, resulting in jaw dislocation. Temporomandibular joint dislocation is commonly reported in association with anesthesia and intubation, but it is not widely recognized as a complication of gastrointestinal endoscopy. This report also reviews the current literature regarding this complication and discusses the potential causes of dislocation, differential diagnoses for jaw pain following endoscopy, and recommendations for prevention. PMID- 27403116 TI - Successful Management of Acute Liver Failure Patients Waiting for Liver Transplantation by On-Line Hemodiafiltration with an Arteriovenous Fistula. AB - On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middle-aged Japanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF. PMID- 27403118 TI - Efficacy of Self-Expandable Metallic Stent Inserted for Refractory Hemorrhage of Duodenal Cancer. AB - Because of advances in the technology of gastrointestinal endoscopy and improvements in the quality of stents, it has become routine to place a stent as palliative therapy for malignant gastrointestinal obstruction. On the other hand, stent placement for malignant gastrointestinal hemorrhage has scarcely been reported, although it may be performed for hemorrhage of the esophageal varicose vein. We recently experienced a patient with refractory hemorrhage from an unresectable duodenal cancer who underwent placement of a self-expandable metallic stent (SEMS) and thereafter had no recurrence of the hemorrhage. A 46 year-old man underwent laparotomy to radically resect a cancer in the third portion of the duodenum, which invaded widely to the superior mesenteric vein and its branches and was considered unresectable. After stomach-partitioning gastrojejunostomy was performed, chemotherapy was initiated according to the regimen of chemotherapy of far advanced gastric cancer. One year and 4 months after induction of chemotherapy, gastrointestinal hemorrhage occurred. Upper gastrointestinal endoscopy revealed the hemorrhage oozing from the duodenal cancer, and endoscopic hemostasis, such as injection of hypertonic saline epinephrine and argon plasma coagulation, was unsuccessful. Twenty days after emergence of the hemorrhage, an endoscopic covered SEMS was placed with confirmation by fluoroscopy. Immediately after placement of the stent, the tarry stool stopped and the anemia ceased to progress. The recurrence of the hemorrhage has not been confirmed without migration of the stent. SEMS is an effective hemostatic procedure for malignant refractory hemorrhage. PMID- 27403119 TI - Efficacy of Combined Mesalazine Plus Corticosteroid Enemas for Diversion Colitis after Subtotal Colectomy for Ulcerative Colitis. AB - Diversion colitis is a benign inflammatory process that occurs in any part of the large bowel excluded from the fecal stream by a diverting colostomy. While most of the patients with diversion colitis usually are asymptomatic, a minority has abdominal pain and rectal discharge of blood or mucus. A 65-year-old Japanese man was diagnosed as having diversion colitis with ulcerative colitis at 4 months after subtotal colectomy. Corticosteroid and mesalazine enemas were started nonsynchronously. A proctoscopy after 2 months showed no response. Prednisolone injections were started at 1.0 mg/kg daily, but the mucosal inflammation still failed to improve. A combined mesalazine 1 g plus prednisolone sodium phosphate 20 mg enema was started once daily. The rectal bleeding and endoscopic findings improved. Finally proctectomy and ileal pouch-anal anastomosis were successfully performed. A combined mesalazine plus corticosteroid enema may be effective in patients with diversion colitis associated with ulcerative colitis. PMID- 27403120 TI - Duodenal Adenocarcinoma Diagnosed from a Biopsy Specimen of a Depressed Lesion Obtained by Magnifying Endoscopy. AB - Biopsies are necessary for the management of duodenal tumors. However, the most suitable targets for biopsy are not known. An 82-year-old woman who regularly visited our hospital for rheumatoid arthritis underwent abdominal ultrasonography. This screening revealed a dilated pancreatic duct. Magnetic resonance cholangiopancreatography was performed, and dilatation of the pancreatic duct was confirmed. The patient underwent duodenoscopy to investigate the possibility of obstruction of the papilla of Vater. The examination revealed an elevated lesion around the papilla of Vater. Endoscopic ultrasonography and a 20-MHz mini-probe were used to investigate the depth of the invasion. The common bile and pancreatic ducts were intact. The mucosal and submucosal borders were indistinct; however, the border between the submucosa and muscularis propria was clear, suggesting that the muscularis propria was intact. Magnifying endoscopy was used to examine the surface of the elevated lesion, which revealed a depressed lesion. A biopsy specimen of the depressed lesion was taken, and the tumor was diagnosed as an adenocarcinoma. Another biopsy specimen from a non depressed lesion was diagnosed as an adenoma. The patient was diagnosed with duodenal adenocarcinoma, and was recommended surgery. She declined surgery and was followed up for 34 months. Because it is possible for depressed lesions of duodenal tumors to be adenocarcinomas, biopsy specimens should be obtained from depressed lesions of duodenal tumors. PMID- 27403121 TI - A Case of Gastrointestinal Stromal Tumor That Underwent Endoscopic Ultrasound Guided Aspiration with a 25-Gauge Biopsy Needle. AB - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed to obtain specimens for pathological analysis. For this procedure, 19-gauge (19G), 22-guage (22G), and 25-guage (25G) needles are available. The needles are classified into aspiration type and biopsy type. A 56-year-old woman underwent upper gastrointestinal endoscopy that showed a 38-mm-diameter submucosal tumor. The elevated lesion was diagnosed as a submucosal tumor of the stomach. Contrast enhanced computed tomography showed a low-density area on the luminal surface of the gastric wall, which was covered with a thin layer of gastric mucosa. EUS showed a hypoechoic lesion in the submucosal layer. Color Doppler image showed a pulsating vascular signal extending into the center of the hypoechoic lesion from the periphery. EUS-FNA was performed with a 25G biopsy needle. The specimen tissue consisted of spindle-shaped cells. The cells were positive for CD117 and CD34. The submucosal tumor was diagnosed as a gastrointestinal stromal tumor. PMID- 27403123 TI - Lymphoepithelial Cyst of the Pancreas. AB - Lymphoepithelial cyst (LEC) of the pancreas is an extremely rare, benign pancreatic cystic lesion that is difficult to differentiate preoperatively from other cystic pancreatic lesions. LEC may have malignant potential. Here, we describe a case of LEC of the pancreas - initially suspected to be a mucinous cyst neoplasm - in an elderly man presenting with abdominal pain, who went on to have a distal pancreatectomy and splenectomy. We also review the relevant literature and discuss implications for the diagnosis and management of this rare lesion. PMID- 27403122 TI - Pancreatic Acinar Cell Carcinoma. AB - Pancreatic acinar cell carcinoma (ACC) is a rare malignant neoplasm that accounts for 1-2% of all pancreatic neoplasms. Here we report two cases of ACC and describe their clinical features, the therapies used to treat them, and their prognosis. The first patient was a 65-year-old woman who had an abdominal CT scan for a urinary infection. Fortuitously, a rounded and well-delimited corporeal pancreatic tumor was discovered. An endoscopic ultrasound (EUS)-guided fine needle aspiration revealed an ACC. During the puncture, a hypoechoic cavity appeared inside the lesion, corresponding to a probable necrotic area. Treatment consisted of a distal splenopancreatectomy. The second patient was a 75-year-old man who complained of abdominal pain. An abdominal CT scan showed a cephalic pancreatic lesion and two hepatic metastases. An EUS-guided fine needle aspiration showed a pancreatic ACC. The patient received chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen), which enabled an objective response after 6 cycles. PMID- 27403125 TI - Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report. AB - Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy. PMID- 27403124 TI - Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage. AB - A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551 554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations. PMID- 27403126 TI - Improvement of Microstomia in Scleroderma after Carbon Dioxide Laser Treatment. AB - Limited mouth opening (LMO) is a frequent complication of systemic sclerosis (SS). Its management is complex and there are limited treatment options. We report four patients with SS and severe LMO [interincisal distance (IID) <30 mm] treated with pulsed carbon dioxide (CO2) laser. Pulsed CO2 laser treatment of the white lips was performed after all patients had signed a written informed consent in the absence of alternative treatment. Treatment was carried out under locoregional anaesthesia using a Sharplan 30C CO2 laser in the Silk Touch(r) resurfacing mode. One to three laser sessions were performed at intervals of 8-12 months between sessions. Assessments were performed at 3 and 12 months with measurement of the IID using a ruler, calculation of the Mouth Handicap in Systemic Sclerosis (MHISS) scale and global evaluation by the patients. Adverse events were also reported. In all four patients, an improvement in IID occurred 3 months after the first session with a mean gain of +5 mm (range: 2-7). At 12 months, a mean gain of +8.5 mm (range: 7-10) in IID was observed. The MHISS score decreased by a mean of *14 (range: 11-17). All patients showed improvement of lip flexibility or mouth opening, allowing better phonation and mastication and easier dental care. Adverse effects were transient erythema and/or dyschromia. CO2 laser appears to be effective and well tolerated in the improvement of LMO in SS. PMID- 27403127 TI - Partial Response in an RRx-001-Primed Patient with Refractory Small-Cell Lung Cancer after a Third Introduction of Platinum Doublets. AB - Small-cell lung cancer (SCLC), initially exquisitely sensitive to first-line cisplatin/etoposide, invariably relapses and acquires a multidrug chemoresistant phenotype that generally renders retreatment with first-line therapy both futile and counterproductive. This report presents the case of a 77-year-old Caucasian male with extensive-stage refractory SCLC who was restarted on platinum doublets as part of a clinical trial called TRIPLE THREAT (NCT02489903) involving pretreatment with the epi-immunotherapeutic agent RRx-001, and who achieved a partial response after only 4 cycles. The patient had received a platinum drug twice before, in 2009 for a diagnosis of non-small-cell lung cancer (squamous cell carcinoma) and in 2015 for SCLC, suggesting that RRx-001 pretreatment may sensitize or resensitize refractory SCLC patients to first-line chemotherapy. PMID- 27403128 TI - Human Epidermal Growth Factor Receptor 2 (HER-2/neu)-Directed Therapy for Rare Metastatic Epithelial Tumors with HER-2 Amplification. AB - CASE 1: A 67-year-old Asian female was diagnosed with locally advanced high-grade salivary duct carcinoma in June 2011. Molecular analysis revealed human epidermal growth factor receptor 2 (HER-2) amplification. She received adjuvant therapy with carboplatin/paclitaxel/ trastuzumab and maintenance of trastuzumab. Upon disease progression, trastuzumab could not be continued due to lack of financial coverage. Instead, she was treated with compassionate use of lapatinib from April 2013 and standard 5-fluorouracil. Her disease ultimately progressed and she expired later in 2013. CASE 2: A 68-year-old Asian male was diagnosed with extramammary Paget's disease of the scrotum with HER-2 amplification in May 2011. He received 6 cycles of adjuvant trastuzumab/docetaxel/carboplatin followed by maintenance trastuzumab, which was changed to compassionate use of lapatinib as his insurance did not cover further administration of trastuzumab. He showed clinical benefits from single-agent lapatinib and a combination of lapatinib/capecitabine upon progression to the single-agent lapatinib. Ultimately, he was started on ado-trastuzumab emtansine, which was approved at that time by the FDA for HER-2-positive breast cancer progressed on trastuzumab. He is having clinical and radiographic complete response based on current imaging and normalization of his tumor markers. CONCLUSION: HER-2-targeted therapy should be considered for tumors with HER-2 amplification. In our case series, we would like to emphasize this approach in other rare histologies. Specifically, our patient with extramammary Paget's disease of the scrotum represents the first reported case of a non-breast, non-gastric tumor with HER-2 overexpression with complete clinical and radiographic response to HER-2-targeted therapy. PMID- 27403129 TI - A Late Case of Ischemic Cerebral Event after Resection of a Left Atrial Myxoma. AB - Atrial myxoma is one of the most common primary cardiac tumors reported in the literature. In very rare instances, stroke has been the sequelae after a myxomatous tumor resection. We report this unique case of late ischemic cerebral event in a 46-year-old female some days after resection of a left atrial myxoma. PMID- 27403130 TI - Seronegative Neuromyelitis Optica: A Case Report of a Hispanic Male. AB - Neuromyelitis optica (NMO) is a rare disease, common in white females and rarely reported in Hispanic males. It is usually associated with recurrent demyelinating spectrum that is autoimmune in nature. The diagnosis is usually confirmed by antibody biomarkers; however, they can be negative and lead to more dilemma in diagnosis. Furthermore, the course of disease and prognosis are different in seronegative as compared to seropositive NMO. Treatment is similar in both subgroups with new approaches under investigation for seronegative NMO patients. We present an interesting case of a 37-year-old Hispanic male who presented with sudden onset of lower extremity weakness, numbness, blurry vision, and urinary retention. Magnetic resonance imaging (MRI) of the thoracic spine showed multiphasic demyelinating process involving the thoracic spinal cord. His brain MRI also revealed changes suggesting optic neuritis. The patient met the criteria for diagnosis of NMO by having optic neuritis and myelitis by imaging studies despite having negative aquaporin-4 antibodies (AQP4-Ab). His condition improved after plasma exchange. NMO can be difficult to distinguish from acute multiple sclerosis in the early stages of the disease. Having AQP4-Ab testing is important for diagnosis with imaging studies; however, negative antibody results cannot exclude the diagnosis, but rather group it in seronegative subtype. Ongoing studies and research suggest that seronegative NMO might have a different pathophysiology, manifestation, and prognosis. PMID- 27403131 TI - Nerve Ultrasound as a Decisive Tool in Nonsystemic Vasculitic Neuropathy: A Case Report. AB - INTRODUCTION: The additional value of peripheral nerve ultrasound in acquired immune-mediated neuropathies has recently been reported. Its impact in vasculitic neuropathy is yet to be defined. We report electrophysiological and nerve ultrasound studies in a patient with nonsystemic vasculitic neuropathy at first diagnosis and in response to immunosuppression. CASE REPORT: A 44-year-old female presented with painful neuropathy and weakness of the intrinsic hand muscles. Electrodiagnostic studies revealed severe axonal neuropathy of the nerves of the left arm. On nerve ultrasound, massive and patchy swelling of these nerves was detected. Clinical, laboratory, and radiological evidence of nonneuromuscular involvement and systemic vasculitic diseases was absent. Hence, nonsystemic vasculitic neuropathy was diagnosed without the possibility of histological verification. After 6 months of systemic immunosuppression with steroids and cyclophosphamide, clinical symptoms improved in parallel with neurosonography. In contrast, electrophysiological studies remained pathological despite clinical improvement. CONCLUSIONS: Neurosonography studies in nonsystemic vasculitic neuropathy are rare but might be an ancillary technique to guide noninvasive diagnosis and therapeutic monitoring. Morphological analysis of nerves and changes in response to treatment could be well visualized. Additionally, neurosonography might be useful to target nerve biopsy. PMID- 27403132 TI - Bilateral Serous Retinal Detachment Associated with Inferior Posterior Staphyloma Treated with Scleral Shortening and Vitrectomy. AB - PURPOSE: We report a case of bilateral serous retinal detachment (SRD) associated with inferior posterior staphyloma (IPS) treated successfully with scleral shortening. PATIENT AND METHODS: A 63-year-old woman presented with bilateral visual loss due to an SRD with IPS. The best-corrected visual acuity levels were 0.6 (20/30) and 0.5 (20/40) in the right and left eye, respectively. The patient underwent vitrectomy and scleral shortening in the right eye. The lamellar scleral crescent was resected 4 mm in width from the 5- to 8-o'clock positions. Seven interrupted 5-0 polyester sutures were placed at the edge of the lamellar scleral crescent. After 25-gauge three-port vitrectomy, the sutures were tightened. Optical coherence tomography showed decreased curvature at the staphyloma border. The choroidal thickness decreased in the superior flat portion of the fundus and increased slightly in the staphyloma. The SRD resolved 3 months postoperatively. The best-corrected visual acuity in the right eye improved to 0.8 (20/25) 6 months postoperatively. Angiography 6 months postoperatively showed decreased diffuse dye leakage at the fovea in the right eye; indocyanine green angiography did not show marked changes. DISCUSSION: Scleral shortening with vitrectomy changes the eye wall shape, may improve the retinal pigment epithelial integrity, and may be a treatment option for SRD with IPS. PMID- 27403133 TI - Spontaneous Corneal Clearance in the Presence of a Partially Detached Graft after Non-Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To report the explantation of a detached and opaque donor disc as an alternative to secondary keratoplasty in a case of persistent graft detachment followed by spontaneous clearance of the recipient cornea after non-Descemet stripping automated endothelial keratoplasty (non-DSAEK). RESULTS: Four months after graft explantation, BSCVA was 0.5 and endothelial cell density (ECD) was 1,221 cells/m(2). After 13 months, BSCVA was still 0.6 while ECD had fell to 800, and 2 years later, the endothelium decompensated. BSCVA was 0.3 and ECD was not measurable. CONCLUSIONS: To our knowledge this is the first report of explantation of an endothelial graft as an alternative to re-keratoplasty in a case of spontaneous corneal clearance. This minimally invasive treatment may be considered in similar cases. However, due to the ongoing loss of endothelial cells after endothelial keratoplasty, a re-keratoplasty may still be needed in the long term. PMID- 27403135 TI - Geriatric cardiology and the Great Wall International Congress of Cardiology 2015. PMID- 27403134 TI - Physical Exercise with Multicomponent Cognitive Intervention for Older Adults with Alzheimer's Disease: A 6-Month Randomized Controlled Trial. AB - AIMS: This study aimed to investigate the effect of 6-month physical exercise with a multicomponent cognitive program (MCP) on the cognitive function of older adults with moderate to severe Alzheimer's disease (AD). METHODS: We included 33 participants with AD in a 6-month randomized controlled trial. The intervention group participated in physical exercise and received a MCP. The control group received only the MCP. Before and after the intervention, cognitive outcomes were assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS cog), Mini-Mental State Examination, and the Clock Drawing Test. Physical performance was evaluated by exercise time, the number of pedal rotation, total load, grip strength, and the Berg Balance Scale (BBS). RESULTS: In all cognitive measures, there were no significant improvements between the two groups after 6 months in the baseline value-adjusted primary analysis. However, the ADAS-cog score was significantly lower between the two groups in secondary analysis adjusted for baseline value, age, sex, and education years. All physical outcomes were significantly higher in the intervention group except for total load compared with baseline measurements. CONCLUSION: This study indicates that it is possible to improve cognitive function in older adults with moderate to severe AD through 6-month physical exercise with a multicomponent cognitive intervention. PMID- 27403136 TI - Relationship between ADP-induced platelet-fibrin clot strength and anti-platelet responsiveness in ticagrelor treated ACS patients. AB - BACKGROUND: Ticagrelor provides enhanced antiplatelet efficacy but increased risk of bleeding and dyspnea. This study aimed to display the relationship between ADP induced platelet-fibrin clot strength (MAADP) and clinical outcomes in acute coronary syndrome (ACS) patients treated by ticagrelor. METHODS: Consecutive Chinese-Han patients with ACS who received maintenance dose of ticagrelor on top of aspirin were recruited. After 5-day ticagrelor maintenance treatment, MAADP measured by thrombelastography (TEG) were recorded for the evaluation of ticagrelor anti-platelet reactivity. Pre-specified cutoffs of MAADP > 47 mm for high on-treatment platelet reactivity (HTPR) and MAADP < 31 mm for low on treatment platelet reactivity (LTPR) were applied for evaluation. The occurrences of primary ischemic cardiovascular events (including a composite of cardiac death, non-fatal myocardial infarction and stroke), the Thrombolysis in Myocardial Infarction (TIMI) defined bleeding events, and ticagrelor related dyspnea were recorded after a follow-up of three months. RESULTS: Overall, 176 ACS patients (Male: 79.55%, Age: 59.91 +/- 10.54 years) under ticagrelor maintenance treatment were recruited. The value of MAADP ranged from 4.80% to 72.90% (21.27% +/- 12.07% on average), with the distribution higher skewed towards the lower values. Using the pre-specific cutoffs for HTPR and LTPR, seven patients (3.98%) were identified as HTPR and 144 patients (81.82%) as LTPR. After a follow-up of three months in 172 patients, major cardiovascular events occurred in no patient, but TIMI bleeding events in 81 (47.09%) with major bleedings in three patients. All patients with major bleedings were classified as LTPR. Ticagrelor related dyspnea occurred in 31 (18.02%) patients, with 30 (21.28%) classified as LTPR and no one as HTPR (P = 0.02). CONCLUSIONS: In ticagrelor treated ACS patients, MAADP measured by TEG might be valuable for the prediction of major bleeding and ticagrelor related dyspnea. Due to the small number of patients with HTPR after ticagrelor maintenance treatment, larger scale study should be warranted to verify the relationship between MAADP defined HTPR and ticagrelor related ischemic events. PMID- 27403137 TI - Impact of severe left ventricular dysfunction on mid-term mortality in elderly patients undergoing transcatheter aortic valve implantation. AB - BACKGROUND: Whether patients with reduced left ventricular function present worse outcome after transcatheter aortic valve implantation (TAVI) is controversial. The aim of this study was to assess the impact of baseline severe impairment of left ventricular ejection fraction (LVEF) on mortality after TAVI. METHODS: Six hundred-forty-nine patients with aortic stenosis underwent TAVI with the CoreValve system (92.8%) or the Edwards SAPIEN valve system (7.2%). Baseline LVEF was measured by the echocardiographic Simpson method. The impact of LVEF <= 30% on mortality was assessed by Cox regression. RESULTS: Patients with LVEF <= 30% (n = 63), as compared to those with LVEF > 30% (n = 586), had a higher prevalence of NHYA class > 2 (P < 0.001) and presented with a higher Euroscore (P < 0.001). Procedural success was similar in both groups (98.4% vs. 97.2%, P = 1). After a median follow-up of 436 days (25(th)-75(th) percentile, 357-737 days), all-cause mortality [23.8% vs. 23.7%, P = 0.87, hazard ratios (HR): 0.96, 95% confidence intervals (CI): 0.56-1.63] and cardiac mortality (19.1% vs. 17.6%, P = 0.89, HR: 1.04, 95% CI: 0.57-1.90) were similar in patients with LVEF <= 30% as compared to those with LVEF > 30%. Thirty-day all-cause mortality was not significantly different between the two groups (11.1% vs. 6.3%, P = 0.14, HR: 1.81, 95% CI: 0.81-4.06). Patients with LVEF <= 30% had a trend toward higher risk of 30-day cardiac mortality (11.1% vs. 5.3%; P = 0.06, HR: 2.16, 95% CI: 0.95-4.90), which disappeared after multivariable adjustment (P = 0.22). CONCLUSIONS: Baseline severe impairment of LVEF is not a predictor of increased short-term and mid-term mortality after TAVI. Selected patients with severe impairment of left ventricular function should not be denied TAVI. PMID- 27403138 TI - Homocysteine is associated with the progression of non-culprit coronary lesions in elderly acute coronary syndrome patients after percutaneous coronary intervention. AB - BACKGROUND: The influence of homocysteine (Hcy) on the migration and proliferation of vascular smooth muscle cells has been well established. However, the impact of Hcy levels on the progression of non-culprit coronary lesions (NCCLs) is controversial. This study aims to evaluate whether the plasma level of Hcy is related to the progression of NCCLs after percutaneous coronary stent implantation in elderly patients with acute coronary syndrome (ACS). METHODS: A total of 223 elderly patients (>= 65 years old) with ACS undergoing stent implantation and follow-up coronary angiography were enrolled. Laboratory determination comprised of blood sample evaluation for Hcy was carried out before baseline coronary intervention. The patients were classified into two groups according to the blood Hcy tertiles (>= 15 mmol/L or < 15 mmol/L). Patients were followed up for 12.2 months. NCCL progression was assessed by three-dimensional quantitative coronary angiography. RESULTS: A significantly higher ratio of NCCL progression was observed in the group with baseline Hcy concentrations above 15 mmol/L compared to the group with concentrations below 15 mmol/L (41/127, 32.3% vs. 14/96, 14.6%, P = 0.002). Multivariate Cox regression analysis showed that Hcy and diabetes mellitus were independent risk factors for NCCL progression. The crude hazard ratio (HR) of NCCL progression for Hcy level was 1.056 (95% CI: 1.01 1.104, P = 0.015). The adjusted HR of NCCL progression for Hcy level was 1.024 (95% CI: 1.007-1.042, P = 0.007). The adjusted HR of NCCL progression for diabetes mellitus was 1.992 (95% CI: 1.15-3.44, P = 0.013). CONCLUSIONS: Hcy is an independent risk factor for NCCL progression after 12 months of follow-up in elderly patients with ACS who has undergone percutaneous coronary stenting. PMID- 27403139 TI - Vessel healings after stenting with different polymers in STEMI patients. AB - BACKGROUND: Different stents implantation in ST-segment elevation myocardial infarction (STEMI) patients may influence the long term prognosis by affecting vessel healings after stenting. The aim of this study was to evaluate the vessel healings after implantation of drug eluting stents (DES) with biodegradable or durable polymer or of bare-metal stents (BMS) in patients with acute STEMI. METHODS: This study included 50 patients, who underwent follow up angiogram and optical coherence tomography (OCT) assessment about one year after percutaneous coronary intervention (PCI) for STEMI. According to the initial stents types, these patients were classified to durable (n = 19) or biodegradable polymer sirolimus-eluting stents (n = 15), or BMS (n = 16) groups. The conditions of stent struts coverage and malapposition were analyzed with OCT technique. RESULTS: A total of 9003 struts were analyzed: 3299, 3202 and 2502 from durable or biodegradable polymer DES, or BMS, respectively. Strut coverage rate (89.0%, 94.9% and 99.3%, respectively), malapposition presence (1.7%, 0.03% and 0 of struts, respectively) and average intimal thickness over struts (76 +/- 12 um, 161 +/- 30 um and 292 +/- 29 um, respectively) were significantly different among different stent groups (all P < 0.001). CONCLUSIONS: Vessel healing status in STEMI patients is superior after implantation of biodegradable polymer DES than durable polymer DES, while both are inferior to BMS. PMID- 27403140 TI - Positive correlation between plasma PCSK9 and tissue factors levels in patients with angiographically diagnosed coronary artery disease and diabetes mellitus. AB - BACKGROUND: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL C). Both oxidized LDL and tissue factor (TF) contributed to the development of prothrombotic state. The present study aims to explore the relationship between plasma level of PCSK9 and that of TF in patient with coronary artery disease (CAD). METHODS: From July 2013 to March 2014, we enrolled 197 consecutive patients who underwent coronary angiography because of suspected CAD at Beijing Anzhen Hospital in this study. All patients had no history of using lipid lowering medication. Of these 197 patients (131 male and 66 female, mean age 56.9 +/- 11.8 years), 81 had angiographically diagnosed CAD. Clinical data were collected. Plasma PCSK9 and TF were measured using enzyme-linked immunosorbent assay (ELISA). Levels of plasma PCSK9 and TF were compared and their correlation analyzed among different patient groups. RESULTS: Both plasma levels of PCSK9 (279.8 +/- 60.4 ug/L vs. 216.5 +/- 45.3 ug/L, P < 0.01) and TF (156.4 +/- 26.6 ug/mL vs. 112.1 +/- 38.3 ug/L, P < 0.01) were significantly higher in patients with CAD, as compared with those without CAD. Correlation analysis showed plasma level of PCSK9 was significantly correlated with that of TF in both patients with and without CAD. However, multivariate regression analysis after adjustment for age, gender, smoking, alcohol, hypertension and hyperlipidemia showed that only in CAD patients with type 2 diabetes mellitus, there was significant positive correlation between plasma levels of PCSK9 and TF (beta = 0.353, P < 0.01). CONCLUSIONS: The plasma level of PCSK9 is independently and positively associated with that of TF in CAD patients with diabetes mellitus, but not in those without diabetes mellitus. Further study is needed to investigate the underlying mechanism. PMID- 27403141 TI - Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium. AB - OBJECTIVE: Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (I to) and slow delayed rectifier potassium current (I Ks). METHODS: The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record I to and I Ks in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. RESULTS: The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of I to and I Ks in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of I to in M layers and partly inhibit the channel openings of I to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of I Ks channel in Epi and Endo layers without affecting its activation. CONCLUSIONS: Our study gives partially explanation about the mechanisms of transmural inhibition of I to and I Ks channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings. PMID- 27403142 TI - Attitudes towards acceptance of an innovative home-based and remote sensing rehabilitation protocol among cardiovascular patients in Shantou, China. AB - BACKGROUND: Cardiac rehabilitation (CR) protocols have diversified to include home-based cardiac tele-rehabilitation (HBCTR) as an alternative to hospital based or center-based CR. To adopt the use of home-based cardiac tele rehabilitation, it is necessary to assess cardiac patients' attitudes towards acceptance of such e-health technology, especially in China where knowledge of such technology is deficient. METHODS: Interviews were conducted in the First Affiliated Hospital of Shantou University Medical College, Shantou, China. After percutaneous coronary interventional (PCI) surgery, patients completed the survey. RESULTS: Among the 150 patients, only 13% had ever heard of HBCTR. After an introduction of our HBCTR program, 60% of patients were willing to participate in the program. From our multivariate analysis of questionnaire data, age (OR: 0.92, 95% CI: 0.86-0.98; P = 0.007), average family monthly income (OR: 0.13, 95% CI: 0.05-0.34; P < 0.001), education level (OR: 0.24, 95% CI: 0.10-0.59; P = 0.002) and physical exercise time (OR: 0.19, 95% CI: 0.06-0.56; P = 0.003) were independent predictors for acceptance of HBCTR. From the reasons for participation, patients selected: enhanced safety and independence (28.3%), ability to self-monitor physical conditions daily (25.4%), and having automatic and emergency alert (23.1%). Reasons for refusal were: too cumbersome operation (34.3%) and unnecessary protocol (19.4%). CONCLUSIONS: Most patients lacked knowledge about HBCTR but volunteered to participate after they have learned about the program. Several personal and life-style factors influenced their acceptance of the program. These indicate that both improvement of technology and better understanding of the program will enhance active participation. PMID- 27403143 TI - Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin aldosterone system. AB - BACKGROUND: Obstructive sleep apnea (OSA) is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin angiotensin-aldosterone system (RAAS). We meta-analyzed the effects of OSA on plasma levels of RAAS components. METHODS: Full-text studies published on MEDLINE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea hypopnea index or respiratory disturbance index >= 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the I (2) statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. RESULTS: The meta-analysis included 13 studies, of which 10 reported results on renin (n = 470 cases and controls), 7 on angiotensin II (AngII, n = 384), and 9 on aldosterone (n = 439). AngII levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI: 2.00-4.79, P < 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension (mean differences = 1.32 ng/dL, 95% CI: 0.58-2.07, P = 0.0005). Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL (95% CI: 0.88-1.82, P < 0.00001) emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. CONCLUSIONS: OSA is associated with higher AngII and aldosterone levels, especially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity. PMID- 27403144 TI - Additional manual thrombus aspiration for ST-segment elevation myocardial infarction during percutaneous coronary intervention: an updated meta-analysis. AB - BACKGROUND: The clinical efficacy and safety of adjunctive thrombus aspiration (TA) in patients with ST-segment elevation myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) remain controversial. METHODS: Twenty five eligible randomized controlled trials were included to compare the use of thrombus aspiration (TA) with PCI and PCI-only for STEMI. The primary endpoint was all-cause mortality and death. The secondary endpoints were major adverse cardiac events (MACE), recurrent infarction (RI), target vessel revascularization (TVR), stent thrombosis (ST), perfusion surrogate markers and stroke. RESULTS: TIMI flow grade 3 and MBG 2-3 were significantly increased in the TA plus PCI arm compared with the PCI-only arm [relative risk (RR): 1.05, 95% confidence intervals (CI): 1.02-1.09, P = 0.004] and (RR: 1.68, 95% CI: 1.40-2.00, P < 0.001), respectively. There were no significant differences in all-cause mortality, MACEs, TVR and ST rates between the two groups. The RI rate was lower in the TA plus PCI arm than that in the PCI-only arm with short-term follow-up duration (RR: 0.60, 95% CI: 0.38-0.96, P = 0.03), but there was no significant difference in RI incidence over the medium- or long-term follow-up periods (RR: 1.00, 95% CI: 0.77-1.29, P = 0.98), and (RR: 0.96, 95% CI: 0.81-1.15, P = 0.69), respectively. There were statistically significant differences in the rates of crude stroke and stroke over the medium- or long-term follow-up periods and the crude stroke rate in the TA plus PCI (RR: 1.60, 95% CI: 1.08-2.38, P = 0.02) and (RR: 1.43, 95% CI: 1.03-1.98, P = 0.03), respectively; this was not observed between the two arms during the short-term follow-up period (RR: 1.47, 95% CI: 0.97-2.21, P = 0.07). CONCLUSIONS: Routine TA-assisted PCI in STEMI patients can improve myocardial reperfusion and get limited benefits related to the clinical endpoints, which may be associated with stroke risk. PMID- 27403146 TI - Angina rapidly improved with a plant-based diet and returned after resuming a Western diet. PMID- 27403145 TI - Cardiac toxicity of trastuzumab in elderly patients with breast cancer. AB - Breast cancer (BC) is diagnosed in >= 65 year old women in about half of cases. Experts currently recommend that systemic therapy is offered to elderly patients with BC, if, based on their overall conditions and life expectancy, it can be reasonably anticipated that the benefits will outweigh the risks of treatment. Like for young subjects, the monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), trastuzumab, represents a valid therapeutic option when BC over-expresses this receptor. Unfortunately, administration of trastuzumab is associated with the occurrence of left ventricular dysfunction and chronic heart failure (CHF), possibly because of interference with the homeostatic functions of HER-2 in the heart. Registry-based, retrospective analyses have reported an incidence of CHF around 25% in elderly women receiving trastuzumab compared with 10%-15% in those not given any therapy for BC, and the risk of CHF has been estimated to be two-fold higher in > 60-65 year old trastuzumab users vs. non-users. Extremely advanced age and preexisting cardiac disease have been shown to predispose to trastuzumab cardiotoxicity. Therefore, selection of older patients for treatment with trastuzumab should be primarily based on their general status and the presence of comorbidities; previous chemotherapy, especially with anthracyclines, should be also taken into account. Once therapy has started, efforts should be made to ensure regular cardiac surveillance. The role of selected biomarkers, such as cardiac troponin, or new imaging techniques (three-dimension, tissue Doppler echocardiography, magnetic resonance imaging) is promising, but must be further investigated especially in the elderly. Moreover, additional studies are needed in order to better understand the mechanisms by which trastuzumab affects the old heart. PMID- 27403147 TI - Elevated uric acid level: the chicken or the egg? PMID- 27403148 TI - The relation between epicardial fat thickness and metabolic syndrome. PMID- 27403149 TI - Does it make sense evaluating cardiac resynchronization therapy in the elderly regardless of the type of the device? PMID- 27403150 TI - Symptom clusters and quality of life among patients with advanced heart failure. AB - OBJECTIVES: To identify symptom clusters among patients with advanced heart failure (HF) and the independent relationships with their quality of life (QoL). METHODS: This is the secondary data analysis of a cross-sectional study which interviewed 119 patients with advanced HF in the geriatric unit of a regional hospital in Hong Kong. The symptom profile and QoL were assessed by using the Edmonton Symptom Assessment Scale (ESAS) and the McGill QoL Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Hierarchical regression analysis was used to examine the independent relationships with their QoL, after adjusting the effects of age, gender, and comorbidities. RESULTS: The patients were at an advanced age (82.9 +/- 6.5 years). Three distinct symptom clusters were identified: they were the distress cluster (including shortness of breath, anxiety, and depression), the decondition cluster (fatigue, drowsiness, nausea, and reduced appetite), and the discomfort cluster (pain, and sense of generalized discomfort). These three symptom clusters accounted for 63.25% of variance of the patients' symptom experience. The small to moderate correlations between these symptom clusters indicated that they were rather independent of one another. After adjusting the age, gender and comorbidities, the distress (beta = -0.635, P < 0.001), the decondition (beta = 0.148, P = 0.01), and the discomfort (beta = -0.258, P < 0.001) symptom clusters independently predicted their QoL. CONCLUSIONS: This study identified the distinctive symptom clusters among patients with advanced HF. The results shed light on the need to develop palliative care interventions for optimizing the symptom control for this life-limiting disease. PMID- 27403151 TI - A Citrus bergamia Extract Decreases Adipogenesis and Increases Lipolysis by Modulating PPAR Levels in Mesenchymal Stem Cells from Human Adipose Tissue. AB - The aim of this research was to assess the impact of a well-characterized extract from Citrus bergamia juice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 MUg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added with Citrus bergamia for further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma), adipocytes fatty acid-binding protein (A-FABP), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5'-adenosine monophosphate-activated protein kinase (AMPK)alpha1/2, and pAMPKalpha1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay. Citrus bergamia extract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes. Citrus bergamia extract could be a useful natural product for improving adipose mobilization in obesity-related disorders. PMID- 27403152 TI - Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR. AB - The inflammatory response after polymer-based drug-eluting stent (DES) placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activators thiazolidinedione (TZD) remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO) on circulating peripheral blood mononuclear cells (MNCs) in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO) or placebo (control; Con) treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinase-9 (MMP-9) were significantly decreased in PIO group compared to the Con group (P = 0.035, 0.011, 0.008, and 0.012, resp.). DES-induced mRNA expressions of IL-6, TNF-alpha, and MMP-9 in circulating MNC were significantly blocked by PIO (P = 0.031, 0.012, and 0.007, resp.). In addition, PIO markedly inhibited DES-enhanced NF-kappaB function and DES-blocked PPAR-gamma activity. Mechanically, DES induced PPAR-gamma ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-kappaB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era. PMID- 27403153 TI - A Methodology for the Hybridization Based in Active Components: The Case of cGA and Scatter Search. AB - This work presents the results of a new methodology for hybridizing metaheuristics. By first locating the active components (parts) of one algorithm and then inserting them into second one, we can build efficient and accurate optimization, search, and learning algorithms. This gives a concrete way of constructing new techniques that contrasts the spread ad hoc way of hybridizing. In this paper, the enhanced algorithm is a Cellular Genetic Algorithm (cGA) which has been successfully used in the past to find solutions to such hard optimization problems. In order to extend and corroborate the use of active components as an emerging hybridization methodology, we propose here the use of active components taken from Scatter Search (SS) to improve cGA. The results obtained over a varied set of benchmarks are highly satisfactory in efficacy and efficiency when compared with a standard cGA. Moreover, the proposed hybrid approach (i.e., cGA+SS) has shown encouraging results with regard to earlier applications of our methodology. PMID- 27403154 TI - Novel Virtual Environment for Alternative Treatment of Children with Cerebral Palsy. AB - Cerebral palsy is a severe condition usually caused by decreased brain oxygenation during pregnancy, at birth or soon after birth. Conventional treatments for cerebral palsy are often tiresome and expensive, leading patients to quit treatment. In this paper, we describe a virtual environment for patients to engage in a playful therapeutic game for neuropsychomotor rehabilitation, based on the experience of the occupational therapy program of the Nucleus for Integrated Medical Assistance (NAMI) at the University of Fortaleza, Brazil. Integration between patient and virtual environment occurs through the hand motion sensor "Leap Motion," plus the electroencephalographic sensor "MindWave," responsible for measuring attention levels during task execution. To evaluate the virtual environment, eight clinical experts on cerebral palsy were subjected to a questionnaire regarding the potential of the experimental virtual environment to promote cognitive and motor rehabilitation, as well as the potential of the treatment to enhance risks and/or negatively influence the patient's development. Based on the very positive appraisal of the experts, we propose that the experimental virtual environment is a promising alternative tool for the rehabilitation of children with cerebral palsy. PMID- 27403155 TI - A Prebiotic Formula Improves the Gastrointestinal Bacterial Flora in Toddlers. AB - We aimed to investigate the effect of enriched 3-prebiotic formula (including inulin, fructooligosaccharides, and galactooligosaccharides) on toddler gut health by measuring fecal microbiota. Our results revealed that the consumption of 3-prebiotic formula three times per day giving total intake of 1.8 g prebiotic ingredients significantly showed the increased number of probiotic Bifidobacterium spp. colonies and the reduced populations of both C. perfringens and total anaerobic bacteria on the fecal bacterial flora in toddlers at 18~36 months. In addition, total organic acids in the fecal samples significantly increased which improves the utilization of bifidus under acidic conditions after consumption of the 3-prebiotic formula. Therefore, using the formula enriched with prebiotic may maintain gut health in toddlers. PMID- 27403156 TI - Advances in Therapeutic Cholangioscopy. AB - Nowadays, cholangioscopy is an established modality in diagnostic and treatment of pancreaticobiliary diseases. The more widespread use and the recent development of new technologies and accessories had renewed the interest of endoscopic visualization of the biliary tract, increasing the range of indications and therapeutic procedures, such as diagnostic of indeterminate biliary strictures, lithotripsy of difficult bile duct stones, ablative techniques for intraductal malignancies, removal of foreign bodies and gallbladder drainage. These endoscopic interventions will probably be the last frontier in the near future. This paper presents the new advances in therapeutic cholangioscopy, focusing on the current clinical applications and on research areas. PMID- 27403157 TI - Comparison of Inflammatory Response to Transgastric and Transcolonic NOTES. AB - Aims. The aim of our study was to determine the physiologic impact of NOTES and to compare the transgastric and transcolonic approaches. Methods. Thirty pigs were randomized to transgastric, transcolonic, or laparoscopic peritoneoscopy. Blood was drawn and analyzed for C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin- (IL-) 1beta, IL-6, WBCs, and platelets. Results. Endoscopic closure with an OTSC was successful in all 20 animals. The postoperative course was uneventful in all animals. CRP values rose on day 1 in all animals and slowly declined to baseline levels on day 14 with no differences between the groups (P > 0.05, NS). The levels of TNF-alpha were significantly increased in the transcolonic group (P < 0.01); however this difference was already present prior to the procedure and remained unchanged. No differences were observed in IL1-beta and IL-6 values. There was a temporary rise of WBC on day 1 and of platelets on day 7 in all groups (P > 0.05, NS). Conclusions. Transgastric, transcolonic, and laparoscopic peritoneoscopy resulted in similar changes in systemic inflammatory markers. Our findings do not support the assumption that NOTES is less invasive than laparoscopy. PMID- 27403158 TI - Screening Driving Transcription Factors in the Processing of Gastric Cancer. AB - Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer. Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed. Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer. Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis. PMID- 27403160 TI - Transperitoneal Laparoscopic Pyelopyelostomy for Retrocaval Ureter without Excision of the Retrocaval Segment: Experience on Three Cases. AB - Introduction. Retrocaval ureter is a rare congenital anomaly. Open surgery was the classic treatment for this condition. Laparoscopy is currently an admitted procedure to treat many urological diseases. The objective of our study is to present our experience and discuss the safety and the feasibility of transperitoneal laparoscopic pyelopyelostomy for treatment of retrocaval ureter (RCU). Materials and Methods. Three symptomatic patients underwent laparoscopic repair for RCU in our department. The diagnosis was suspected on the computed tomography scan (CT) and confirmed on ascending pyelography. After placement of a JJ stent, and, using the transperitoneal approach, the retro peritoneum was exposed; the ureter was identified in both sides of the vena cava. The retrocaval segment was entirely mobilized and pulled from behind of the vena cava after section of renal pelvis. A pyelopyelostomy was done in a normal anatomic position. Results. All operations were achieved laparoscopically without conversion to open surgery. The mean operative time was 140 minutes (110-190). No intraoperative complication occurred. Blood loss was less than 50 mL in all patients. The mean hospital stay was 5 days (4-6 days). All patients were symptom free after surgery and had reduction of hydronephrosis in control imagery. Conclusion. Laparoscopy seems safe, feasible, and reproducible in managing retrocaval ureter. PMID- 27403159 TI - MDMA Impairs Response to Water Intake in Healthy Volunteers. AB - Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID- 27403161 TI - Stroke Risk among Patients with Type 2 Diabetes Mellitus in Zhejiang: A Population-Based Prospective Study in China. AB - Objective. This study aimed to explore the incidence of stroke and stroke subtypes among patients with type 2 diabetes mellitus (T2DM) based on the long term surveillance data in Zhejiang, China, during 2007 to 2013. Materials and Methods. During January 1, 2007, and December 31, 2013, a total of 327,268 T2DM and 307,984 stroke patients were registered on Diabetes and Stroke Surveillance System, respectively. Stroke subtypes were classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. The incidence of stroke and stroke subtypes was calculated by standardized incidence ratio (SIRs) with 95% confidence intervals (CIs) compared with general population. Results. The incidence of stroke and stroke subtypes among patients with T2DM was significantly higher than in general population. Stroke risk was found significantly increased with an SIR of 3.87 (95% CI 3.76 3.99) and 3.38 (95% CI 3.27-3.48) in females and males, respectively. The excess risk of stroke was mainly attributable to the significantly higher risk of cerebral infarctions with the risk for T2DM being four times that for general population. Conclusions. The relationship between stroke and T2DM was strong, especially in female. The incidence of stroke and stroke subtypes among patients with T2DM was up to 3-fold higher than in general population in Zhejiang province, especially the subtype of cerebral infarctions. PMID- 27403162 TI - Treating Woman with Myo-Inositol Vaginal Suppositories Improves Partner's Sperm Motility and Fertility. AB - Motility is the feature that allows spermatozoa to actively reach and penetrate the female gamete during fertilization. When this function is altered, and especially decreased, troubles in conceiving may occur. In this study, we demonstrated that treating fertile women with myo-inositol (MI) vaginal suppositories ameliorated their partners' sperm motility and also positively affected their conceiving capacity, without changes in cervical mucus structural and biochemical characteristics. Indeed, by means of the postcoital test on female cervical mucus, a significant improvement especially in progressive sperm motility was recorded after MI suppository use. Concomitantly, after MI treatment, a reduction of immotile spermatozoa percentage was observed. Importantly, MI vaginal supplementation positively correlated with a pregnancy for 5 of the 50 couples enrolled in the study, leading us to speculate that this substance may substantially contribute to create in the cervical mucus an ideal milieu that makes spermatozoa more motile and functionally able to fertilize. Even though the detailed mechanism is still unclear, these results should encourage MI vaginal use for the clinical improvement of male infertility, through their partners. PMID- 27403163 TI - Color Stability of the Bulk-Fill Composite Resins with Different Thickness in Response to Coffee/Water Immersion. AB - We aimed to evaluate the color stability of bulk-fill and conventional composite resin with respect to thickness and storage media. Twenty specimens of a conventional composite resin (6 mm diameter and 2 mm thick) and 40 specimens of the bulk-fill Tetric EvoCeram composite resin at two different thicknesses (6 mm diameter and 2 mm thick or 4 mm thick, n = 20) were prepared. The specimens were stored in distilled water during the study period (28 d). Half of the specimens were remained in distilled water and the other half were immersed in coffee solution 20 min/d and kept in distilled water between the cycles. Color changes (DeltaE) were measured using the CIE L (*) a (*) b (*) color space and a digital imaging system at 1, 7, 14, and 28 days of storage. Data were analyzed using Two way ANOVA and Tukey's HSD post hoc test (P < 0.05). Composite resins showed significant increase in color changes by time (bulk-fill > conventional; P < 0.001). Coffee exhibited significantly more staining susceptibility than that of distilled water (P < 0.001). There was greater color changes with increasing the increment thickness, which was significant at 14 (P < 0.001) and 28 d (P < 0.01). Color change of bulk-fill composite resin was greater than that of the conventional one after coffee staining and is also a function of increment thicknesses. PMID- 27403164 TI - Pregnancy in Sickle Cell Disease Is a Very High-Risk Situation: An Observational Study. AB - Sickle cell disease is a serious genetic disorder affecting 1/235 births in French Guiana. This study aimed to describe the follow-up of pregnancies among sickle cell disease patients in Cayenne Hospital, in order to highlight the most reported complications. 62 records of pregnancies were analyzed among 44 females with sickle cell disease, between 2007 and 2013. Our results were compared to those of studies conducted in Brazil and Guadeloupe. There were 61 monofetal pregnancies and 2 twin pregnancies, 27 pregnancies among women with SS phenotype, 30 SC pregnancies, and five S-beta pregnancies. The study showed that the follow up of patients was variable, but no maternal death was found. We also noted that the main maternofetal complications of pregnancies were anemia (36.5%), infection (31.7%), vasoocclusive crisis (20.6%), preeclampsia (17.5%), premature birth (11.1%), intrauterine growth retardation (15.9%), abnormal fetal heart rate (14.3%), and intrauterine fetal death (4.8%). Pregnancies were more at risk among women with SS phenotype. Pregnancy in sickle cell disease patients requires a supported multidisciplinary team including the primary care physician, the obstetrician, and the Integrated Center for Sickle Cell Disease. PMID- 27403165 TI - ST Segment Elevation with Normal Coronaries. AB - Noncardiac causes should be kept in the differential while evaluating ST elevation on EKG. Rarely abdominal pathologies like acute pancreatitis can present with ST elevation in the inferior leads. Once acute coronary syndrome is ruled out by emergent cardiac catheterization alternative diagnosis should be sorted. Abdominal pathologies, like acute pancreatitis and acute cholecystitis, can present with ST elevation in the inferior leads. Treating the underlying condition would result in resolution of these EKG changes. PMID- 27403166 TI - Transcranial Direct Current Stimulation Modulates Neurogenesis and Microglia Activation in the Mouse Brain. AB - Transcranial direct current stimulation (tDCS) has been suggested as an adjuvant tool to promote recovery of function after stroke, but the mechanisms of its action to date remain poorly understood. Moreover, studies aimed at unraveling those mechanisms have essentially been limited to the rat, where tDCS activates resident microglia as well as endogenous neural stem cells. Here we studied the effects of tDCS on microglia activation and neurogenesis in the mouse brain. Male wild-type mice were subjected to multisession tDCS of either anodal or cathodal polarity; sham-stimulated mice served as control. Activated microglia in the cerebral cortex and neuroblasts generated in the subventricular zone as the major neural stem cell niche were assessed immunohistochemically. Multisession tDCS at a sublesional charge density led to a polarity-dependent downregulation of the constitutive expression of Iba1 by microglia in the mouse cortex. In contrast, both anodal and, to an even greater extent, cathodal tDCS induced neurogenesis from the subventricular zone. Data suggest that tDCS elicits its action through multifacetted mechanisms, including immunomodulation and neurogenesis, and thus support the idea of using tDCS to induce regeneration and to promote recovery of function. Furthermore, data suggest that the effects of tDCS may be animal- and polarity-specific. PMID- 27403167 TI - Cryopreservation of Bone Marrow Mononuclear Cells Alters Their Viability and Subpopulation Composition but Not Their Treatment Effects in a Rodent Stroke Model. AB - The systemic administration of autologous bone marrow (BM) derived mononuclear cells (MNCs) is under investigation as a novel therapeutic modality for the treatment of ischemic stroke. Autologous applications raise the possibility that MNCs could potentially be stored as a banked source. There have been no studies that investigate the effects of cryopreservation of BM-MNCs on their functional abilities in stroke models. In the present study, C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAo) for 60 minutes and then divided into two treatment groups: fresh MNCs versus cryopreserved MNCs. BM-MNCs were collected at 22 hours after MCAo and were stored in liquid nitrogen for 12 months in cryopreserved MNCs group. BM-MNCs cellular viability, composition, and phenotype of the various subpopulations of mice BM-MNCs were evaluated by flow cytometry, and the behavioral recovery of stroke animals was tested with freshly harvested MNCs versus cryopreserved MNCs by corner test and ladder rung test. We found that long-term cryopreservation negatively impacts the cellular viability of bone marrow MNCs. Cryopreservation also alters the cellular composition of various subpopulations within the MNCs. However, despite the changes observed in cryopreserved cells, both fresh and frozen MNCs have similar beneficial effect on behavioral and histological outcomes. PMID- 27403168 TI - Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts. AB - Reprogramming can occur by the introduction of key transcription factors (TFs) as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) combined with a chromatin remodeling medium (CRM) induced expression of a number of definitive endoderm and early and late pancreatic marker genes. When CRM was omitted, endoderm/pancreatic marker genes were not induced. Furthermore, treatment with DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (5AZA) CRM did not affect gene expression changes, and when 5AZA was combined with TSA, no further increase in gene expression of endoderm, pancreatic endoderm, and endocrine markers was seen over levels induced with TSA alone. Interestingly, TSA-CRM did not affect expression of pluripotency and hepatocyte genes but induced some mesoderm transcripts. Upon removal of TSA-CRM, the endoderm/pancreatic gene expression profile returned to baseline. Our findings underscore the role epigenetic modification in transdifferentiation of one somatic cell into another. However, full reprogramming of fibroblasts to beta cells will require combination of this approach with TF overexpression and/or culture of the partially reprogrammed cells under beta-cell specific conditions. PMID- 27403169 TI - Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer's Disease Treatment: An In Vitro Study. AB - The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer's disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Abeta) peptide. We determined whether DPSCs can secrete the Abeta-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Abeta-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Abeta peptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degrading Abeta 1-42 in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer's disease. PMID- 27403170 TI - Knowledge about Epilepsy and Attitudes toward Students with Epilepsy among Middle and High School Teachers in Kuwait. AB - Background and Objectives. Attitudes toward students with epilepsy and epilepsy related knowledge of teachers are crucial for child's safety in the school. The aim of this study was to evaluate teachers' knowledge and attitudes toward epilepsy. Methods. This cross-sectional study included 824 teachers from 24 randomly selected middle and high schools. Scale of Attitudes Toward Persons with Epilepsy (ATPE) was modified to assess teachers' knowledge about epilepsy and attitudes toward students with epilepsy. Results. Median knowledge score about epilepsy was 5 (out of 13), while median attitude score was 10 (out of 15). Both knowledge and attitude median scores were significantly higher in senior teachers with longer teaching experience and in respondents who dealt with a person with epilepsy. There was significant association between knowledge score and attitude score (p < 0.01). Logistic regression showed that significant variables, independently associated with poor knowledge after adjusting for possible confounders, were not having a family member with epilepsy (p = 0.009), unawareness of life circumstances of persons with epilepsy (p = 0.048), and a poor attitude score (p < 0.001). Conclusion. School teachers in Kuwait have relatively poor knowledge about epilepsy but have positive attitudes toward students with epilepsy. A number of historical and stigmatizing ideas about epilepsy still exist. It is recommended to provide teachers with information about handling seizures in the educational setting through development and implementation of epilepsy education programs. PMID- 27403171 TI - Oral Candidiasis among Cancer Patients Attending a Tertiary Care Hospital in Chennai, South India: An Evaluation of Clinicomycological Association and Antifungal Susceptibility Pattern. AB - Oropharyngeal candidiasis is one of the common manifestations seen in cancer patients on cytotoxic therapy and invasion into deeper tissues can occur if not treated promptly. Emergence of antifungal drug resistance is of serious concern owing to the associated morbidity and mortality. The present study aims at evaluation of clinicomycological association and antifungal drug susceptibility among the 180 recruited patients with cancer on chemotherapy and/or radiotherapy with signs or symptoms suggestive of oral candidiasis. Speciation and antifungal susceptibility was done by Microbroth dilution method for fluconazole, Itraconazole, and Amphotericin B as per standard microbiological techniques. Chi square test was used for statistical analysis (p < 0.05 was considered statistically significant). Candida albicans was the predominant species isolated (94) (58%) followed by Candida tropicalis (34) (20.9%). Fluconazole and Itraconazole showed an overall resistance rate of 14% and 14.8%, respectively. All the isolates were susceptible to Amphotericin B. There was a significant association between the presence of dry mouth and isolation of Candida (p < 0.001). Such clinicomicrobiological associations can help in associating certain symptoms with the isolation of Candida. Species level identification with in vitro antifungal susceptibility pattern is essential to choose the appropriate drug and to predict the outcome of therapy. PMID- 27403172 TI - Prevalence of Asthma and Respiratory Symptoms among University Students in Sari (North of Iran). AB - BACKGROUND: Despite widely available data about childhood asthma, there are limited data about the prevalence of asthma among young adults in Iran. The aim of this study was to determine the prevalence of asthma and respiratory symptoms among medical students in the city of Sari in Northern Iran. MATERIALS AND METHODS: The prevalence of asthma and respiratory symptoms was studied using a standard questionnaire. Based on the information obtained from the questionnaires, the study participants were divided into two groups of asthmatics and non-asthmatics. Pulmonary function tests including forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before, and after salbutamol inhalation were measured in all subjects with asthma and approximately 10% of those without asthma. RESULTS: A total of 1,011 subjects (374 males, 637 females) participated in this study. Asthma was found in 3.5% of the subjects (3.2% males and 3.6% females). The 12-month prevalence of wheezing, coughing at rest, coughing at night, breathlessness at rest, exercise-induced wheezing, and exercise-induced coughing in the entire study population was 11.1%, 12.4%, 13.4%, 13.3%, 17.7%, and 16.7%, respectively. The prevalence of all asthma-related symptoms was significantly higher among asthmatics compared to non-asthmatics. Moreover, asthmatic subjects showed lower FEV1 and FVC values compared to nonasthmatic subjects (P<0.001). Smoking and family history of asthma were statistically significant risk factors for developing asthma. CONCLUSION: The high prevalence of asthma related symptoms in the present study strongly suggests that asthma is under diagnosed and under treated among participants. PMID- 27403173 TI - Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients. AB - BACKGROUND: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. MATERIALS AND METHODS: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients' demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. RESULTS: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. CONCLUSION: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID- 27403174 TI - Intention to Quit Smoking and Associated Factors in Smokers Newly Diagnosed with Pulmonary Tuberculosis. AB - BACKGROUND: Several studies have shown that smoking, as a modifiable risk factor, can affect tuberculosis (TB) in different aspects such as enhancing development of TB infection, activation of latent TB and its related mortality. Since willingness to quit smoking is a critical stage, which may lead to quit attempts, being aware of smokers' intention to quit and the related predictors can provide considerable advantages. MATERIALS AND METHODS: In this cross-sectional study, subjects were recruited via a multi-stage cluster sampling method. Sampling was performed during 2012-2014 among pulmonary TB (PTB) patients referred to health centers in Tehran implementing the directly observed treatment short course (DOTS) strategy and a TB referral center. Data analysis was conducted using SPSS version 22 and the factors influencing quit intention were assessed using bivariate regression and multiple logistic regression models. RESULTS: In this study 1,127 newly diagnosed PTB patients were studied; from which 284 patients (22%) were current smokers. When diagnosed with TB, 59 (23.8%) smokers quit smoking. Among the remaining 189 (76.2%) patients who continued smoking, 52.4% had intention to quit. In the final multiple logistic regression model, living in urban areas (OR=8.81, P=0.003), having an office job (OR= 7.34, P=0.001), being single (OR=4.89, P=0.016) and a one unit increase in the motivation degree (OR=2.60, P<0.001) were found to increase the intention to quit smoking. CONCLUSION: The study found that PTB patients who continued smoking had remarkable intention to quit. Thus, it is recommended that smoking cessation interventions should be started at the time of TB diagnosis. Understanding the associated factors can guide the consultants to predict patients' intention to quit and select the most proper management to facilitate smoking cessation for each patient. PMID- 27403175 TI - Continuous Positive Airway Pressure Compliance in Patients with Obstructive Sleep Apnea. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a common condition in adults. In most cases, first-line therapy includes treatment with positive airway pressure devices. However, because of discomfort, continuous positive airway pressure (CPAP) compliance is often poor. To determine the willingness of patients to use CPAP device, the relationship of demographic and polysomnographic variables with tolerance and the willingness to use CPAP, was evaluated. MATERIALS AND METHODS: In this cross-sectional study, 120 OSA patients who were treated with CPAP in Baqiyatallah Hospital, Tehran, Iran, were selected by convenience sampling. Polysomnographic variables, willingness to use CPAP for short and long periods of time and possible complications were evaluated. RESULTS: One hundred-twenty cases with a mean age of 53+/-10.3 years were assessed. The mean Epworth Sleepiness Scale (ESS) score was 11.9 +/- 6.2 in CPAP users versus 11.8+/-6.1 in patients who did not use CPAP. The willingness to use CPAP for short-term was significantly different between the two groups (P=0.008). The average minimum oxygen saturation rate of patients was 75.21% in CPAP users versus 71.63% in non CPAP users. Also, the average desaturation index was higher in CPAP users (54.5 vs. 44.98). The mean ESS was 14.03 +/- 6.19 in those who accepted long-term treatment versus 8.85 +/- 4.89 (P=0.003). Skin wounds and rhinitis were reported in 4.1% and 4.1% of patients, respectively. CONCLUSION: It is concluded that high CPAP compliance rates are achievable through comprehensive CPAP therapy. PMID- 27403176 TI - Comparison between Total Parenteral Nutrition Vs. Partial Parenteral Nutrition on Serum Lipids Among Chronic Ventilator Dependent Patients; A Multi Center Study. AB - BACKGROUND: Malnutrition is very common among chronically hospitalized patients, especially those in the intensive care unit (ICU). Identifying the patients at risk and providing suitable nutritional support can prevent and/or overcome malnutrition in them. Total parenteral nutrition (TPN) and partial parenteral nutrition (PPN) are two common routes to deliver nutrition to hospitalized patients. We conducted a multicenter, prospective double blind randomized controlled trial to evaluate the benefits and compare their adverse effects of each method. MATERIALS AND METHODS: 97 patients were enrolled and divided into two groups based on the inclusion criteria. Serum protein, serum albumin, serum transferrin, and total lymphocyte count were measured on days 7 and 14. RESULTS: We did not find any statistically significant differences in clinical status or laboratory values between the two groups but there were significant improvements in measured lab values between days 7 and 14 (p<0.005) indicating improved nutritional status in each groups. CONCLUSION: This study shows that both TPN and PPN can be used safely in chronic ICU patients to provide nutritional support and prevent catabolic state among chronic critically ill patients. We need to develop precise selection criteria in order to choose the patients who would benefit the most from TPN and PPN. In addition, appropriate laboratory markers are needed to monitor the metabolic requirements of the patients and assess their progress. PMID- 27403177 TI - Estimation of Ten-Year Survival of Patients with Pulmonary Tuberculosis Based on the Competing Risks Model in Iran. AB - BACKGROUND: Tuberculosis (TB) is a chronic bacterial disease, which despite the presence of effective drug strategies, still remains a serious health problem worldwide. Estimation of survival rate is an appropriate indicator for prognosis in patients with pulmonary TB. Therefore, this research was designed with the aim of accurate estimation of the survival of patients by taking both the death event and relapse into consideration. MATERIALS AND METHODS: Based on a retrospective cohort study, information of 2,299 patients with pulmonary TB that had been referred to and treated in Masih Daneshvari Hospital from 2005 to 2015 was reviewed. To estimate the survival of patients with pulmonary TB, the competing risks model, which considered death and relapse as competing events, was used. In addition, the effect of factors affecting the cumulative incidence function (CIF) of death event and relapse was also examined. RESULTS: The effect of risk factors on the CIF of death events and relapse showed that patients' age, marital status, contact with TB patients, adverse effect of drugs, imprisonment and HIV positivity were factors that affected the CIF of death. Meanwhile, sex, marital status, imprisonment and HIV positivity were factors affecting the CIF of relapse (P <0.05). Considering death and relapse as competing events, survival estimation in pulmonary TB patients showed that survival in this group of patients in the first, third, fifth and tenth year after treatment was 39%, 14%, 7% and 0%, respectively. CONCLUSION: The use of competing risks model in survival analysis of patients with pulmonary TB with consideration of competing events, enables more accurate estimation of survival. PMID- 27403178 TI - Association of Neutrophil to Lymphocyte Ratio and Pulmonary Hypertension in Sarcoidosis Patients. AB - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has emerged as a new marker of inflammation associated with the severity of several respiratory and cardiac diseases. MATERIALS AND METHODS: We investigated whether the degree of systemic inflammation in sarcoidosis patients as measured by the NLR is associated with pulmonary hypertension (PH). RESULTS: A NLR > 3.5 occurred with a significantly higher frequency in sarcoidosis patients with PH (50% vs. 24%, P=0.016) yielding a sensitivity of 50%, specificity of 78%, positive predictive value (PPV) of 41.9% and negative predictive value (NPV) of 81.4% and remained independently associated with PH in multivariate analysis (OR: 3.254, 95% CI: 1.094-9.678, P=0.034). CONCLUSION: We conclude that level of inflammation in sarcoidosis patients may be associated with the development of PH. Owing to the relatively good specificity and NPV, NLR may be a good negative test, which is a simple, inexpensive and widely available in office-based setting to predict the risk of PH in sarcoidosis patients. PMID- 27403179 TI - Prevalence of HLA-B*5701 and Its Relationship with Abacavir Hypersensitivity Reaction in Iranian HIV-Infected Patients. AB - BACKGROUND: Hypersensitivity reaction (HSR) is a major adverse effect of abacavir (ABC), which occurs in 5-8% of Caucasians. The relationship between Human Leukocyte Antigen (HLA) and ABC HSR has been reported in various populations. It has been proposed to administer ABC only to HLA-B*5701 negative patients to avoid this reaction. The purpose of this study was to assess the prevalence of HLA B*5701 in Iranian HIV positive patients. We also sought to find the relationship between this allele with ABC HSR in patients who received the medication. MATERIALS AND METHODS: We screened patients for HLA-B*5701 allele using SybrGreen real time PCR-melting method on blood samples from HIV positive patients who were referred to our hospital. The quality of the extracted genome was evaluated by B globin housekeeping gene as internal control prior to HLA-B*5701 allele screening. RESULTS: Of 198 HIV-infected patients, 6 (3.0%) had the HLA-B*5701 allele (95% CI, 1%-5%). Among the 28 patients who were given ABC, one individual had the HLA-B*5701 allele and experienced ABC HSR. CONCLUSION: Prevalence of HLA B*5701 in Iranian patients was lower than that in Caucasians but was comparable with that of other Middle Eastern populations. Screening for HLA-B*5701 before ABC administration as part of antiretroviral therapy may reduce the risk of HSR. PMID- 27403180 TI - Mixed Pulmonary Infection with Penicillium notatum and Pneumocystis jiroveci in a Patient with Acute Myeloid Leukemia. AB - Penicillium notatum is a fungus that widely exists in the environment and is often non-pathogenic to humans. However, in immunocompromised hosts it may be recognized as a cause of systemic mycosis. A 44-year-old man with acute myeloid leukemia (AML) was admitted to our hospital with fever and neutropenia. Due to no improvement after initial treatment, he underwent bronchoscopy. The patient was found to have P. notatum and Pneumocystis jiroveci infection, and therefore was given voriconazole, primaquine and clindamycin. The patient was successfully treated and suffered no complications. CONCLUSION: This case highlights P. notatum as a cause of infection in immunocompromised patients. To the best of our knowledge, mixed lung infection with P. notatum and P. jiroveci in a patient with AML has not been previously reported. PMID- 27403181 TI - Spontaneous Right Hemothorax in the Elderly. AB - Rupture of thoracic aortic aneurysm is a life threatening condition. Rupture in the right pleural cavity is extremely rare. We report the case of an 80-year-old man with a spontaneous right hemothorax. Diagnosis was made by computed tomography (CT) scan. He was managed with chest tube and stabilization. The patient died before any surgical intervention. We report this case to emphasize that rupture of aortic aneurysm should be considered in the evaluation of spontaneous hemothorax even if it is right-sided particularly in the elderly. Emergent therapy is necessary to prevent mortality. PMID- 27403182 TI - Tolvaptan: A Novel Diuretic in Heart Failure Management. AB - Heart failure (HF) is still a major problem worldwide with high morbidity and mortality rates. The recently developed medication for HF is still incapable of reducing its morbidity and mortality, and clinical data supporting the efficacy and safety of its mainstay therapy remain insufficient. Arginine-vasopressin (AVP) plays important roles in circulatory and water homeostasis, one of which is water retention through the V2 receptor. In patients with HF, there is an increased level of AVP, contributing to such symptoms as edema, dyspnea, and congestion. Tolvaptan as a selective V2 receptor antagonist, in addition to the conventional therapy, has been shown to cause an increase in net fluid loss, a decrease in body weight, and a reduction in the rate of HF exacerbation. Such evidence has been provided by the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist (ACTIV) in Congestive Heart Failure (CHF), Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), Acute Heart Failure Volume Control Multicenter Randomized (AVCMA), and Study of Ascending Levels of Tolvaptan in hyponatremia 1and 2 (SALT-1 and SALT-2) trials. Tolvaptan can be an alternative diuretic in conjunction with other standard therapies for HF and has already been proved to be able to decrease morbidity and mortality, especially in HF patients with hyponatremia. PMID- 27403183 TI - Coronary Artery Bypass Grafting in Patients with Advanced Left Ventricular Dysfunction: Excellent Early Outcome with Improved Ejection Fraction. AB - BACKGROUND: The prevalence of patients with severe left ventricular dysfunction (LVD) referred for coronary artery bypass grafting (CABG) is increasing. Preoperative LVD is an established risk factor for early and late mortality after revascularization. The aim of the present study was to assess the early outcome of patients with severe LVD undergoing CABG. METHODS: Between December 2012 and November 2014, 145 consecutive patients with severely impaired LV function (ejection fraction <= 30%) undergoing either on-pump or off-pump CABG were enrolled. The primary end point was all-cause mortality. Different variables (preoperative, intraoperative, and postoperative) were evaluated and compared. RESULTS: The mean age of the patients was 58.7 years (range, 34 to 87 years), and 82.8% of the patients were male. The mean preoperative LV ejection fraction was 25.33 +/- 5.07% (10 to 30%), which improved to 26.67 +/- 5.38% (10 to 40%) (p value < 0.001). An average of 3.85 coronary bypass grafts per patient was performed. Significant improvement in mitral regurgitation was also observed after CABG (p value < 0.001). Moreover, 120 patients underwent conventional CABG (82.8%) and 25 patients had off-pump CABG (17.2%). In-hospital mortality was 2.1% (3 patients). Patients who underwent off-pump CABG had higher operative mortality than did those undergoing conventional CABG despite a lower severity of coronary involvement and a significantly lower number of grafts (p value < 0.050). Conversely, morbidity was significantly higher in conventional CABG (p value < 0.050). CONCLUSION: CABG in patients with severe LVD can be performed with low mortality. CABG can be considered a safe and effective therapy for patients with a low ejection fraction who have ischemic heart disease and predominance of tissue viability. PMID- 27403184 TI - Left Ventricular Mass Index and Pulmonary Artery Pressure in Patients with the Obstructive Sleep Apnea Syndrome. AB - BACKGROUND: Sleep apnea is accompanied by some cardiovascular complications. It has even been hypothesized that sleep apnea, itself, can induce some of these complications. Given such controversies, we assessed the left ventricular mass index (LVMI) and systolic pulmonary artery pressure in patients with sleep apnea. METHODS: Through convenience sampling, 56 patients with the obstructive sleep apnea syndrome (OSAS) were included in the present descriptive cross-sectional study. Patients with any past history of hypertension and diabetes mellitus were excluded. The apnea severity was assessed via the polysomnography-derived apnea hypopnea index (AHI). All the patients underwent transthoracic echocardiography. In this cross-sectional study - data regarding age, gender, smoking, systolic and diastolic blood pressures, polysomnographic parameters (AHI, severity of disease, mean heart rate, mean oxygen saturation [SaO2], lowest SaO2, and duration of SaO2 below 90% [d.SaO2 < 90%]), and echocardiographic parameters (systolic pulmonary artery pressure and LVMI) were accumulated and processed. RESULTS: Fifty-two men and 14 women at a mean age of 49.29 +/- 11.79 years participated in this study. Systolic and was significantly high in the severe group compared with the mild group (128.21 +/- 9.73 mmHg vs. 119.23 +/- 12.5 mmHg; p value = 0.007). The LVMI was increased parallel to an increase in the severity of the OSAS, but that increase was not statistically significant (p value = 0.161). The d.SaO2 < 90% was positively correlated with the LVMI, and this relationship remained true after adjustment for the body mass index (r = 0.27; p value = 0.042). CONCLUSION: Severe OSAS was accompanied by a higher blood pressure. The LVMI did not differ significantly between the patients with the OSAS and those who did not suffer from other risk factors of cardiac diseases. PMID- 27403185 TI - Prevalence of Dyslipidemia among Elementary School Children in Birjand, East of Iran, 2012. AB - BACKGROUND: Various studies have indicated that dyslipidemia starts in childhood. There is a relationship between the concentration of blood lipids and atherosclerosis. In this study, we assessed the prevalence of dyslipidemia in elementary school children. METHODS: This cross-sectional study was performed on 1,626 (882 girls and 744 boys) elementary school children aged between 6 and 11 years in Birjand in 2012. Samples were selected through multistage random sampling. The lipid profiles (i.e., cholesterol, triglyceride, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]) of the subjects were measured after 12 hours' fasting. The definition of dyslipidemia was based on the criteria of The American Children Academia in 2011. RESULTS: Dyslipidemia (at least one abnormal level of a serum lipid) was detected in 31% of the children (31.3% of the girls vs. 30.6% of the boys). Total cholesterol was >= 200 mg/dL in 13.4% of the children, LDL-C was >= 130 mg/dL in 8.5%, HDL-C was < 40 mg/dL in 11.3%, and triglyceride was >= 130 mg/dL in 15.3%. The prevalence of hypertriglyceridemia was significantly higher in the females than in the males (16.3% in the girls vs. 13.8% in the boys; p value = 0.01) - while hypercholesterolemia (12.2% in the girls vs. 14.9% in the boys; p value = 0.16), high LDL-C (8.5% in the girls vs. 8.5% in the boys; p value = 0.05), and low HDL-C (12.7% in the girls vs. 9.5% in the boys; p value = 0.1) were not significantly different between the two sexes. CONCLUSION: The prevalence of dyslipidemia was high in the school children in Birjand and, thus, requires preventive measures. PMID- 27403186 TI - Burden of Ischemic Heart Disease Attributable to Low Omega-3 Fatty Acids Intake in Iran: Findings from the Global Burden of Disease Study 2010. AB - BACKGROUND: Dietary risk factors constitute some of the leading risk factors for cardiovascular disease in Iran. The current study reports the burden of ischemic heart disease (IHD) attributable to a low omega-3 fatty acids intake in Iran using the data of the Global Burden of Disease (GBD) Study 2010. METHODS: We used data on Iran for the years 1990, 2005, and 2010 derived from the GBD Study conducted by the Institute for Health Metrics and Evaluation (IHME) in 2010. Using the comparative risk assessment, we calculated the proportion of death, years of life lost, years lived with disability, and disability-adjusted life years (DALYs) caused by IHD attributable to a low omega-3 fatty acids intake in the GBD studies from 1990 to 2010. RESULTS: In 1990, a dietary pattern low in seafood omega-3 fatty acids intake was responsible for 423 (95% uncertainty interval [UI], 300 to 559), 3000 (95% UI, 2182 to 3840), and 4743 (95% UI, 3280 to 6047) DALYs per 100000 persons in the age groups of 15 to 49 years, 50 to 69 years, and 70+ years - respectively - in both sexes. The DALY rates decreased to 250 (95% UI, 172 to 331), 2078 (95% UI, 1446 to 2729), and 3911 (95% UI, 2736 to 5142) in 2010. The death rates per 100000 persons in the mentioned age groups were 9 (95% UI, 6 to 12), 113 (95% UI, 82 to 144), and 366 (95% UI, 255 to 469) in 1990 versus 6 (95% UI, 4 to 7), 76 (95% UI, 53 to 99), and 344 (95% UI, 241 to 453) in 2010. The burden of IHD attributable to diet low in seafood omega-3 was 1.3% (95% UI, 0.97 to 1.7) of the total DALYs in 1990 and 2.0% (95% UI, 1.45 to 2.63) in 2010 for Iran. CONCLUSION: The findings of the GBD Study 2010 showed a declining trend in the burden of IHD attributable to a low omega-3 fatty acids intake in a period of 20 years. Additional disease burden studies at national and sub-national levels in Iran using more data sources are suggested for public health priorities and planning public health strategies. PMID- 27403187 TI - Surgical Treatment of a Catheter-Induced Iatrogenic Dissection of the Right Coronary Artery following Cardiac Catheterization. AB - Iatrogenic dissections of the ascending aorta are an uncommon and severe complication during cardiac catheterization. A 68-year-old female patient underwent diagnostic cardiac catheterization due to non-ST-elevation myocardial infarction. During the procedure, a catheter-induced 360( degrees ) Class I dissection of the right coronary artery occurred. The patient developed severe bradycardia, which was treated with a temporary pacemaker. She underwent an emergency operation with ligation and a saphenous vein graft in the right coronary artery. The postoperative course was uneventful; and on postoperative day 6, she was discharged home. PMID- 27403188 TI - Spontaneous Aortic Dissection Limited to the Sinus of Valsalva: Report of Two Cases. AB - Dissection of the sinus of Valsalva is a rare and life-threatening event. It often occurs during percutaneous coronary intervention in the right coronary artery (RCA). Dissection flap usually involves the RCA and the right sinus of Valsalva. Here we report two extremely rare cases of spontaneous dissection limited to the non-coronary sinus of Valsalva, causing severe aortic valve regurgitation: a male aged 51 years presenting with back pain, weakness, and presyncope and another male aged 71 years presenting with orthopnea and weakness. The dissection was found by transesophageal echocardiography. Surgical treatment was successful for both patients. One year after surgery, both patients were asymptomatic and follow- up transthoracic echocardiography did not show any abnormality. PMID- 27403189 TI - Acute Fulminant Myocarditis Successfully Bridged to Recovery with Left Ventricular Assist Device and Complicated by Flail Mitral Valve. AB - Acute fulminant myocarditis is a life-threatening inflammatory disease of the myocardium characterized by the rapid deterioration of the hemodynamic status of the affected individual. With prompt recognition and appropriate management, complete recovery of ventricular function is likely within a few weeks. We introduce a 28-year-old man with acute fulminant myocarditis, who experienced circulatory collapse following acute angina and dyspnea. The patient had high troponin levels with low ejection fraction and normal coronary arteries. He was successfully bridged to recovery with a left ventricular assist device but was complicated by flail mitral valve. Perioperative myocardial biopsy was also compatible with myocarditis. At 4 months' follow-up, the patient was stable with functional capacity I according to the New York Heart Association's classification. A possible mechanism for this very rare complication is the rupture of the chordal structure secondary to the fragility of an inflamed subvalvular apparatus stretched by a recovered ventricle. PMID- 27403190 TI - Left Main Coronary Artery Aneurysm. AB - Aneurysms of the left main coronary artery are exceedingly rare clinical entities, encountered incidentally in approximately 0.1% of patients who undergo routine angiography. The most common cause of coronary artery aneurysms is atherosclerosis. Angiography is the gold standard for diagnosis and treatment. Depending on the severity of the coexisting coronary stenosis, patients with left main coronary artery aneurysms can be effectively managed either surgically or pharmacologically. We herein report a case of left main coronary artery aneurysm in a 72-year-old man with a prior history of hypertension presenting to our hospital because of unstable angina. The electrocardiogram showed ST-segment depression and T-wave inversion in the precordial leads. All the data of blood chemistry were normal. Echocardiography showed akinetic anterior wall, septum, and apex, mild mitral regurgitation and ejection fraction of 45%. Coronary angiography revealed a saccular aneurysm of the left main coronary artery with significant stenosis in the left anterior descending, left circumflex, and right coronary artery. The patient immediately underwent coronary artery bypass grafting and ligation of the aneurysm. At six months' follow-up, he remained asymptomatic. PMID- 27403191 TI - Infective Pseudoaneurysm of the Anterior Mitral Leaflet Accompanied by Aortic Wall Vegetation. PMID- 27403192 TI - Efficacy of telbivudine with conditional tenofovir intensification in patients with chronic hepatitis B: results from the 2-year roadmap strategy. AB - BACKGROUND: A 2-year roadmap study was conducted to evaluate the efficacy and safety of tenofovir intensification at Week 24 in patients with chronic hepatitis B (CHB) receiving telbivudine. SCOPE: A prospective multicenter study was conducted in treatment-naive patients with hepatitis B e antigen (HBeAg)-positive CHB. All patients received telbivudine (600 mg/day) until Week 24. Thereafter, patients with detectable hepatitis B virus (HBV) DNA (>=300 copies/mL) were administered tenofovir (300 mg/day) plus telbivudine, and patients with undetectable HBV DNA continued telbivudine monotherapy until Week 104. The primary endpoint was the proportion of patients with undetectable HBV DNA (<300 copies/mL) at Weeks 52 and 104. FINDINGS: A total of 105 patients were enrolled in the trial, of which 100 were eligible for efficacy analysis. Undetectable HBV DNA levels were observed at Week 24 in 55 patients who continued on with telbivudine monotherapy. The remaining 45 patients with detectable HBV DNA received tenofovir add-on therapy. With monotherapy, 100% (55/55) and 94.5% (52/55) of patients achieved HBV DNA <300 copies/mL at Weeks 52 and 104, respectively; the corresponding values for patients with add-on therapy were 84.4% (38/45) and 93.3% (42/45). Overall, undetectable HBV DNA (<300 copies/mL) was found in 93% (93/100) and 94% (94/100) of patients at Weeks 52 and 104, respectively. HBeAg seroconversion rate was 44.4% (44/99) at Week 104 for the overall patient population. One patient in the monotherapy group and six in the intensification group demonstrated HBsAg clearance at Week 104. HBsAg seroconversion was observed in four patients at Week 104, all belonged to the tenofovir intensification group. Eight patients sustained HBsAg loss during a posttreatment follow-up period of 16 weeks. Alanine aminotransferase (ALT) normalization was constant in the telbivudine monotherapy group, whereas a progressive improvement was observed in the tenofovir intensification group. Two patients in the monotherapy and none in the intensification group experienced viral breakthrough by Week 104. There were no reports of myopathy in either group. The mean changes in estimated glomerular filtration rate (eGFR), estimated using the Modification of Diet in Renal Disease (MDRD) formula, from baseline to Week 104 were +6.145 mL/min/1.73 m(2) (p=0.0230) and +7.954 mL/min/1.73 m(2) (p=0.0154) in the telbivudine monotherapy and tenofovir intensification groups, respectively. The incidence of serious AEs was four in the telbivudine monotherapy and two in the tenofovir intensification group. The main limitation of this study was limited sample size, which made the power of the observation low, and the absence of a comparative subgroup to assess the progression of patients with detectable HBV DNA without treatment intensification. CONCLUSIONS: Data from this 2-year roadmap study confirmed that telbivudine with add-on tenofovir was effective and well tolerated in patients with CHB. Telbivudine was associated with an improvement in eGFR from baseline in both the groups. PMID- 27403193 TI - Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement. AB - OBJECTIVE: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). METHODS: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. RESULTS: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. CONCLUSION: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID- 27403194 TI - Clinical and cost outcomes from different hyaluronic acid treatments in patients with knee osteoarthritis: evidence from a US health plan claims database. AB - BACKGROUND: Intra-articular injection of hyaluronic acid (HA) for knee osteoarthritis (OA) effectively reduces pain and delays total knee replacement (TKR) surgery; however, little is known about relative differences in clinical and cost outcomes among different HA products. OBJECTIVE: To compare disease specific costs and risk of TKR among patients receiving different HA treatments in a commercially insured cohort of patients with knee OA in the USA. METHOD: Retrospective analyses using IMS Health's PharMetrics Plus Health Plan Claims Database were conducted by identifying knee OA patients with claims indicating initiation of HA treatment at an 'index date' during the selection period (2007 2010). Patients were required to be continuously enrolled in the database for 12 months preindex to 36 months postindex. A generalized linear model (GLM) with a gamma distribution and log-link function was used to model aggregate patient based changes in disease-specific costs. A Cox proportional hazards model (PHM) was used to model the risk of TKR. Both multivariate models included covariates such as age, gender, comorbidities, and preindex healthcare costs. RESULTS: 50,389 patients with HA treatment for knee OA were identified. 18,217 (36.2%) patients were treated with HA products indicated for five injections per treatment course (Supartz and Hyalgan). The remainder were treated with HA products indicated for fewer than five injections per treatment course, with 20,518 patients (40.7%) receiving Synvisc; 6,263 (12.4%), Euflexxa; and 5,391 (10.7%), Orthovisc. Synvisc- and Orthovisc-injected patients had greater disease specific costs compared to Supartz/Hyalgan (9.0%, p<0.0001 and 6.8%, p=0.0050, respectively). Hazard ratios (HRs) showed a significantly higher risk of TKR for patients receiving Synvisc compared to Supartz/Hyalgan (HR=1.069, p=0.0009). Patients treated with Supartz/Hyalgan, Euflexxa, and Orthovisc had longer delays to TKR than those treated with Synvisc. CONCLUSION: Analysis of administrative claims data provides real-world evidence that meaningful differences exist among some HA products in disease-specific cost and time to knee replacement surgery. PMID- 27403195 TI - Fire-Needle Moxibustion for the Treatment of Knee Osteoarthritis: A Meta Analysis. AB - Objectives. The aim of this study was to evaluate the effectiveness of fire needle moxibustion as an intervention in the treatment of knee osteoarthritis (KOA). Methods. An updated meta-analysis of randomized controlled trials (RCTs) on fire-needle moxibustion in treating KOA was conducted by searching PubMed, Embase, the Cochrane Library, Web of Science, Wanfang database, and the Chinese Medical Database (CNKI) since their inception through March 2016. The meta analysis was performed using RevMan 5.3. Results. Thirteen RCTs were identified in the systematic study which consisted of 1179 participants. Fire-needle moxibustion treatment group had a statistical significance on recovery rate as well as recovery and marked-improvement rate compared with control group. Subgroup analysis indicated that there was significant difference between fire needle moxibustion group and control group. However, GRADE analysis indicated that the quality of evidence for all outcomes was relatively low. Only two of 13 studies reported adverse reactions (difficulty in movement and intolerance of cold). Conclusion. This meta-analysis suggests that fire-needle moxibustion is more effective than control group in symptom management of KOA. Further high quality trials should be conducted to evaluate the effectiveness of fire-needle moxibustion on KOA. PMID- 27403196 TI - Regulation of MAPKs Signaling Contributes to the Growth Inhibition of 1,7 Dihydroxy-3,4-dimethoxyxanthone on Multidrug Resistance A549/Taxol Cells. AB - 1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is a bioactive compound isolated from Securidaca inappendiculata Hassk. and validated with antiproliferative activities on a panel of cancer cell lines. This study was designed to investigate its growth inhibitory effects on multidrug resistance (MDR) non-small cell lung carcinoma (NSCLC) cell line A549/Taxol and explore the possible linkage between modulation of MAPKs and the bioactivities. Its growth inhibitory potency on the cells was estimated by MTT assay, and flow cytometric analysis was employed to investigate its potential cell cycle arrest and proapoptosis effects. Expressions of hallmark proteins were assessed by Western-Blot method. The results showed A549/Taxol cells were sensitive to XAN. XAN inhibited the proliferation of A549/Taxol cells in the time and concentration dependent manners. It acted as a potent inducer of apoptosis and cell cycle arrest in the cells. Western-Blot investigation validated the proapoptosis and cell cycle arrest activities of XAN and the potential of MDR reversion. Upregulation of p38 by XAN, which accounted for the cell cycle arrest at G2 phase, and the downregulation of ERK associated with the proapoptosis activity were also revealed. Further analysis found p53 may be the central role mediated the bioactivities of MAPKs in A549/Taxol cells. Based on these evidences, a conclusion has been deduced that XAN could be a potential agent for MDR NSCLC therapy targeting specifically MAPKs. PMID- 27403197 TI - JiaWeiDangGui Decoction Ameliorates Proteinuria and Kidney Injury in Adriamycin Induced Rat by Blockade of TGF-beta/Smad Signaling. AB - JiaWeiDangGui (JWDG) decoction has anti-inflammatory and antifibrotic effects, which is used widely for the treatment of various kidney diseases. In previous studies, we have found that JWDG decoction can reduce the quantity of proteinuria, but the mechanism was unknown. Here, we studied the protective effect of JWDG decoction in adriamycin-induced nephropathy on rat. JWDG decoction, at 10 mL/kg/d, 20 mL/kg/d, and 40 mL/kg/d, was orally administered daily for 12 weeks. Therapeutic effects and mechanisms were further examined. The kidney function related biochemical indexes were measured by automatic biochemistry analyzer. The pathomorphological changes were observed using light and transmission electron microcopies. The proteins expressions of podocin, nephrin, collagen IV, and fibronectin (FN) were examined by immunohistochemical staining, and key proteins involved in TGF-beta/Smad signaling were evaluated by RT-PCR and western blotting. Compared with vehicle-treated controls, JWDG decoction decreased the quantity of proteinuria; reduced glomerulosclerotic lesions induced by ADR; and preserved the expression of podocin and nephrin. JWDG decoction also inhibited the expression of the collagen IV, FN, and fibrogenic TGF-beta. Further studies revealed that inhibition of renal fibrosis was associated with the blockade of TGF-beta/Smad signaling and downregulation of snail expression dose dependently. JWDG decoction prevents proteinuria production, podocyte dysfunction, and kidney injury in adriamycin nephropathy by inhibiting TGF-beta/Smad signaling. PMID- 27403198 TI - Effects of Sohamhyoong-Tang on Ovalbumin-Induced Allergic Reaction in BALB/c Mice. AB - IgE-mediated mast cell degranulation and excessive Th2 cells activation are major features of various allergic diseases. Sohamhyoong-tang has been reported to have anti-inflammatory and antibacterial effects. In this study, we investigated the inhibitory effect of Sohamhyoong-tang extract (SHHTE) on allergic symptoms and inflammatory responses in ovalbumin- (OVA-) sensitized BALB/c mice. The mice were sensitized with OVA and alum at 2-week intervals and then orally given SHHTE for 13 days followed by intradermal OVA injection. Administration of SHHTE significantly reduced edema formation and inflammatory-cell infiltration in ear tissues. Total and OVA-specific IgEs as well as proinflammatory cytokine TNF alpha and Th2-associated cytokine IL-4 levels were lower in the SHHTE-treated group than in the vehicle. SHHTE treatment significantly suppressed both mRNA and protein levels of IL-4 and IL-5 in OVA-stimulated splenocytes. SHHTE decreased Th1 (IFN-gamma) and Th17 (IL-17a) cytokine mRNA expression but increased Treg cytokines (IL-10 and TGF-beta1). Moreover, SHHTE significantly inhibited degranulation of RBL-2H3 cell line in a dose-dependent manner. Thus, SHHTE efficiently inhibited the allergic symptoms in an OVA-sensitized mouse model and its action may correlate with the suppression of IgE production by increasing IL 10 and TGF-beta1, which can limit the function of other T helper cells and prevent the release of inflammatory mediators from mast cells. These results suggest that SHHTE could be a therapeutic agent for treating various allergic diseases. PMID- 27403199 TI - Effect of TongXie-YaoFang on Cl(-) and HCO3 (-) Transport in Diarrhea-Predominant Irritable Bowel Syndrome Rats. AB - TongXie-YaoFang (TXYF) can effectively alleviate the symptoms of diarrhea predominant irritable bowel syndrome (D-IBS) patients. However, the curative mechanism has not been fully clarified. The study was designed to investigate the effect of TXYF on the colonic ion transport induced by serotonin (5-HT) in D-IBS rats. A method of multiple stress (neonatal maternal separation (NMS) combined with restraint stress (RS)) was used to induce the D-IBS model. The model rats were randomly divided into two groups: NMS + RS group and TXYF-formula group, and the normal control (no handling) rats were classified as NH group. In the NMS + RS group, the change of short-circuit current (DeltaI sc) induced by 5-HT was lower than that in the NH and TXYF-formula groups. After removing of the extracellular Cl(-) or HCO3 (-) or basolateral Na(+) or blocking the cystic fibrosis transmembrane conductance regulator (CFTR), Na(+)-K(+)-2Cl(-) cotransporter (NKCC), Na(+)-HCO3 (-) cotransporter, Cl(-)/HCO3 (-) exchanger, K(+) channel, or Na(+)/K(+)-ATPase, respectively, there was no difference in 5-HT induced DeltaI sc among the three groups. These data suggest that TXYF can regulate 5-HT-induced Cl(-) and HCO3 (-) secretion, possibly mediated by the combined action of CFTR, NKCC, Na(+)-HCO3 (-) cotransporter, Cl(-)/HCO3 (-) exchanger, K(+) channel, and Na(+)/K(+)-ATPase. PMID- 27403200 TI - Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin Induced Diabetic Male Wistar Rats. AB - Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID- 27403201 TI - Changes of Local Blood Flow in Response to Acupuncture Stimulation: A Systematic Review. AB - Objectives. This systematic review aimed to summarize and evaluate the findings of studies investigating the local microcirculatory effects following acupuncture stimulation. Methods. MEDLINE, EMBASE, OASIS, and Cochrane library were searched to identify randomized controlled trials (RCTs) published before January 30, 2015. Studies demonstrating any type of microcirculation response to manual acupuncture in healthy subjects and patients were included. The risk of bias and the reliability of the experimental conditions were evaluated to determine quality assessment. Results. Eight RCTs met the inclusion criteria; there was at least one acupuncture-induced change in a microcirculatory parameter. Of the seven studies in healthy subjects, four reported significant increases in blood flow following acupuncture compared with control, whereas one other study observed reductions in microcirculation immediately after acupuncture needling. The studies that assessed patients with either fibromyalgia or trapezius myalgia found significant increases in blood flow in the skin and muscle. Additionally, the degree and duration of increases in microcirculation varied depending on the condition of the subjects and the manipulation technique. Conclusions. The current evidence regarding the local effects of acupuncture in terms of blood flow remains insufficient for reliable conclusions due to few well-designed studies. Additional well-designed studies are needed to clarify these issues. PMID- 27403202 TI - Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke. AB - Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID- 27403203 TI - Patient-Specific Computational Models of Coronary Arteries Using Monoplane X-Ray Angiograms. AB - Coronary artery disease (CAD) is the most common type of heart disease in western countries. Early detection and diagnosis of CAD is quintessential to preventing mortality and subsequent complications. We believe hemodynamic data derived from patient-specific computational models could facilitate more accurate prediction of the risk of atherosclerosis. We introduce a semiautomated method to build 3D patient-specific coronary vessel models from 2D monoplane angiogram images. The main contribution of the method is a robust segmentation approach using dynamic programming combined with iterative 3D reconstruction to build 3D mesh models of the coronary vessels. Results indicate the accuracy and robustness of the proposed pipeline. In conclusion, patient-specific modelling of coronary vessels is of vital importance for developing accurate computational flow models and studying the hemodynamic effects of the presence of plaques on the arterial walls, resulting in lumen stenoses, as well as variations in the angulations of the coronary arteries. PMID- 27403204 TI - Toward Psychoinformatics: Computer Science Meets Psychology. AB - The present paper provides insight into an emerging research discipline called Psychoinformatics. In the context of Psychoinformatics, we emphasize the cooperation between the disciplines of psychology and computer science in handling large data sets derived from heavily used devices, such as smartphones or online social network sites, in order to shed light on a large number of psychological traits, including personality and mood. New challenges await psychologists in light of the resulting "Big Data" sets, because classic psychological methods will only in part be able to analyze this data derived from ubiquitous mobile devices, as well as other everyday technologies. As a consequence, psychologists must enrich their scientific methods through the inclusion of methods from informatics. The paper provides a brief review of one area of this research field, dealing mainly with social networks and smartphones. Moreover, we highlight how data derived from Psychoinformatics can be combined in a meaningful way with data from human neuroscience. We close the paper with some observations of areas for future research and problems that require consideration within this new discipline. PMID- 27403205 TI - Circular Helix-Like Curve: An Effective Tool of Biological Sequence Analysis and Comparison. AB - This paper constructed a novel injection from a DNA sequence to a 3D graph, named circular helix-like curve (CHC). The presented graphical representation is available for visualizing characterizations of a single DNA sequence and identifying similarities and differences among several DNAs. A 12-dimensional vector extracted from CHC, as a numerical characterization of CHC, was applied to analyze phylogenetic relationships of 11 species, 74 ribosomal RNAs, 48 Hepatitis E viruses, and 18 eutherian mammals, respectively. Successful experiments illustrated that CHC is an effective tool of biological sequence analysis and comparison. PMID- 27403206 TI - Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation. AB - The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID- 27403207 TI - A Simulation Study to Assess the Effect of the Number of Response Categories on the Power of Ordinal Logistic Regression for Differential Item Functioning Analysis in Rating Scales. AB - Objective. The present study uses simulated data to find what the optimal number of response categories is to achieve adequate power in ordinal logistic regression (OLR) model for differential item functioning (DIF) analysis in psychometric research. Methods. A hypothetical ten-item quality of life scale with three, four, and five response categories was simulated. The power and type I error rates of OLR model for detecting uniform DIF were investigated under different combinations of ability distribution (theta), sample size, sample size ratio, and the magnitude of uniform DIF across reference and focal groups. Results. When theta was distributed identically in the reference and focal groups, increasing the number of response categories from 3 to 5 resulted in an increase of approximately 8% in power of OLR model for detecting uniform DIF. The power of OLR was less than 0.36 when ability distribution in the reference and focal groups was highly skewed to the left and right, respectively. Conclusions. The clearest conclusion from this research is that the minimum number of response categories for DIF analysis using OLR is five. However, the impact of the number of response categories in detecting DIF was lower than might be expected. PMID- 27403208 TI - bSiteFinder, an improved protein-binding sites prediction server based on structural alignment: more accurate and less time-consuming. AB - MOTIVATION: Protein-binding sites prediction lays a foundation for functional annotation of protein and structure-based drug design. As the number of available protein structures increases, structural alignment based algorithm becomes the dominant approach for protein-binding sites prediction. However, the present algorithms underutilize the ever increasing numbers of three-dimensional protein ligand complex structures (bound protein), and it could be improved on the process of alignment, selection of templates and clustering of template. Herein, we built so far the largest database of bound templates with stringent quality control. And on this basis, bSiteFinder as a protein-binding sites prediction server was developed. RESULTS: By introducing Homology Indexing, Chain Length Indexing, Stability of Complex and Optimized Multiple-Templates Clustering into our algorithm, the efficiency of our server has been significantly improved. Further, the accuracy was approximately 2-10 % higher than that of other algorithms for the test with either bound dataset or unbound dataset. For 210 bound dataset, bSiteFinder achieved high accuracies up to 94.8 % (MCC 0.95). For another 48 bound/unbound dataset, bSiteFinder achieved high accuracies up to 93.8 % for bound proteins (MCC 0.95) and 85.4 % for unbound proteins (MCC 0.72). Our bSiteFinder server is freely available at http://binfo.shmtu.edu.cn/bsitefinder/, and the source code is provided at the methods page. CONCLUSION: An online bSiteFinder server is freely available at http://binfo.shmtu.edu.cn/bsitefinder/. Our work lays a foundation for functional annotation of protein and structure based drug design. With ever increasing numbers of three-dimensional protein ligand complex structures, our server should be more accurate and less time consuming.Graphical Abstract bSiteFinder (http://binfo.shmtu.edu.cn/bsitefinder/) as a protein-binding sites prediction server was developed based on the largest database of bound templates so far with stringent quality control. By introducing Homology Indexing, Chain Length Indexing, Stability of Complex and Optimized Multiple-Templates Clustering into our algorithm, the efficiency of our server have been significantly improved. What's more, the accuracy was approximately 2 10 % higher than that of other algorithms for the test with either bound dataset or unbound dataset. PMID- 27403210 TI - The June Issue of the CGJ. PMID- 27403209 TI - Impact of the 'Artful Moments' Intervention on Persons with Dementia and Their Care Partners: a Pilot Study. AB - BACKGROUND: Engaging with art can be valuable for persons living with dementia. 'Artful Moments' was a collaborative project undertaken by the Art Gallery of Hamilton and the Behavioural Health Program at Hamilton Health Sciences that sought to develop and implement a program of arts-based activities for persons in the middle-to-late stages of dementia who exhibit behavioural symptoms and for their accompanying care partners. METHODS: This pilot study employed a qualitative descriptive design. Eight participants were observed during multiple art sessions to evaluate their level of engagement in the program. Care partners also completed a questionnaire describing their experience. Qualitative content analysis was used to identify themes. RESULTS: For program participants, factors that promoted continued interest and engagement in art included: care partner involvement, group activities, opportunities to share opinions, validation of their personhood, and increased engagement over time. Care partners observed improvements in participants' creativity, communication, relationship forming, and task accomplishment, and some reported reduced stress. CONCLUSIONS: 'Artful Moments' promoted engagement and expression in persons in the middle-to-late stages of dementia, as well as having benefits for their care partners. Limitations of the study included a small convenience sample drawn from one hospital setting. PMID- 27403211 TI - Clinical Frailty Scale in an Acute Medicine Unit: a Simple Tool That Predicts Length of Stay. AB - BACKGROUND: Frailty is characterized by increased vulnerability to external stressors. When frail older adults are admitted to hospital, they are at increased risk of adverse events including falls, delirium, and disability. The Clinical Frailty Scale (CFS) is a practical and efficient tool for assessing frailty; however, its ability to predict outcomes has not been well studied within the acute medical service. OBJECTIVE: To examine the CFS in elderly patients admitted to the acute medical ward and its association with length of stay. DESIGN: Prospective cohort study in an acute care university hospital in London, Ontario, Canada, involving 75 patients over age 65, admitted to the general internal medicine clinical teaching units (CTU). MEASUREMENTS: Patient demographics were collected through chart review, and CFS score was assigned to each patient after brief clinician assessment. The CFS ranges from 1 (very fit) to 9 (terminally ill) based on descriptors and pictographs of activity and functional status. The CFS was collapsed into three categories: non-frail (CFS 1 4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-8). Outcomes of length of stay and 90-day readmission were gathered through the LHSC electronic patient record. RESULTS: Severe frailty was associated with longer lengths of stay (Mean = 12.6 +/- 12.7 days) compared to mild-to-moderate frailty (mean = 11.2 +/- 10.8 days), and non-frailty (mean = 4.1 +/- 2.1 days, p = .014). This finding was significant after adjusting for age, sex, and number of medications. Participants with higher frailty scores showed higher readmission rates when compared with those with no frailty (31.2% for severely frail, vs. 34.2% for mild to-moderately frail vs. 19% for non-frail) although there was no significant difference in the adjusted analysis. CONCLUSION: The CFS helped identify patients that are more likely to have prolonged hospital stays on the acute medical ward. The CFS is an easy to use tool which can detect older adults at high risk of complicated course and longer stay. Objective early identification of seniors with frailty in acute care units can help to target interventions to prevent complications and to implement effective discharge planning in high risk older adults. PMID- 27403212 TI - Advantages of a Warfarin Protocol for Long-term Care Pharmacists: a Retrospective Cohort Study. AB - BACKGROUND: Warfarin is an anticoagulant prescribed to 12% of long-term care residents to reduce the risk of thrombo-embolism. This study used indicators to compare warfarin management by pharmacists to usual care. METHODS: This was a retrospective cohort study comparing a pharmacist-managed warfarin protocol with usual care of qualified warfarin recipients at long-term care facilities (two protocol, one control) in Calgary, Alberta. We compared the proportion of international normalized ratio (INR) tests in the range 2.0 to 3.0, time in range, number of tests, and frequency of bleeding at protocol and control sites. Our primary outcome, time in INR therapeutic range, is an indicator for assuring care quality. A cross-sectional survey at these sites compared health professionals' perceptions of workload and effectiveness of warfarin management. RESULTS: Of the 197 residents' charts reviewed in the study period, those on protocol had 45.0 INR tests while those on usual care had 52.7 tests (p = .034, 95% CI for the difference: 0.6 to 14.6 INR tests). No significant difference was found for time in therapeutic range, number of tests in range, or major bleeding events. Of 178 health professionals surveyed, those from protocol facilities were more satisfied with warfarin management (p = .013). Workload and safety were perceived similarly at all sites. INTERPRETATION: Our results suggest that a pharmacist-managed warfarin protocol is as effective as usual care and has advantages pertaining to work satisfaction, knowledge of drug interactions, consistent documentation, and fewer INR tests. Further research on teamwork and coagulation management in long-term care facilities is recommended. PMID- 27403213 TI - Effectiveness of a Core-Competency-based Program on Residents' Learning and Experience. AB - BACKGROUND: The Care of the Elderly (COE) Diploma Program is a six-to-twelve month enhanced skills program taken after two years of core residency training in Family Medicine. In 2010, we developed and implemented a core-competency-based COE Diploma program (CC), in lieu of one based on learning objectives (LO). This study assessed the effectiveness of the core-competency-based program on residents' learning and their training experience as compared to residents trained using learning objectives. METHODS: The data from the 2007-2013 COE residents were used in the study, with nine and eight residents trained in the LO and CC programs, respectively. Residents' learning was measured using preceptors' evaluations of residents' skills/abilities throughout the program (118 evaluations in total). Residents' rating of training experience was measured using the Graduate's Questionnaire which residents completed after graduation. RESULTS: For residents' learning, overall, there was no significant difference between the two programs. However, when examined as a function of the four CanMEDS roles, there were significant increases in the CC residents' scores for two of the CanMEDS roles: Communicator/Collaborator/Manager and Scholar compared to residents in the LO program. With respect to residents' training experience, seven out of ten program components were rated by the CC residents higher than by the LO residents. CONCLUSION: The implementation of a COE CC program appears to facilitate resident learning and training experience. PMID- 27403214 TI - The New Criteria for Alzheimer's Disease - Implications for Geriatricians. AB - Two new sets of criteria for Alzheimer's disease (AD) are now in play, including one set released in 2014, and a proposal for a "new lexicon" for how to describe the disease spectrum. A 2012 Canadian consensus conference said that to then, none of the new criteria or terminology would change primary care practice; that is still likely to be so. For dementia consultants, however, the new criteria pose challenges and offer opportunities. In general, the new criteria see an expanded role for bio-markers. Even so, the evidence base for this remains incomplete. Our understanding of the neuropathological criteria for dementia changed as the evidence base included more community cases. This is likely to inform the experience with biomarkers. At present, each of the criteria specifies an exclusive research role. Still, wider uptake is likely, especially in the United States. Geriatricians should be aware of the fundamental change in the terminology now being employed: AD diagnosis no longer obliges a diagnosis of dementia. Until more data emerge-something to which geriatricians can contribute there is reason to be cautious in the adoption of the new criteria, as they are likely to be least applicable to older adults. PMID- 27403215 TI - [Not Available]. PMID- 27403216 TI - Primary Angioplasty Versus Stenting for Endovascular Management of Intracranial Atherosclerotic Disease Following Acute Ischemic Stroke. AB - BACKGROUND: The future of neuroendovascular treatment for intracranial atherosclerotic disease (ICAD) has been debated since the results of SAMMPRIS reflected poor outcomes following endovascular therapy. There is currently a large spectrum of current management strategies. We compared historical outcomes of patients with ICAD and stroke that were treated with angioplasty-alone versus stent placement. METHODS: We extracted a population from the Nationwide Inpatient Sample (NIS) (2005-2011) and the National Inpatient Sample (NIS) (2012) composed of patients with ICAD and infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with thrombectomy or thrombolysis were excluded. Categorical variables were compared with Chi-squared tests. Binary logistic regression was performed to evaluate mortality while controlling for age, sex, severity, and comorbidities. RESULTS: About 2059 admissions met our criteria. A majority were treated via stent placement (71%). Angioplasty-alone had significantly higher mortality (17.6% vs. 8.4%, P<0.001), but no difference in iatrogenic stroke rate (3.4% vs. 3.6%, P=0.826), compared to stent placement. The adjusted odds ratio of mortality for stented patients was 0.536 (95% CI: 0.381-0.753, P<0.001) in comparison to patients treated with angioplasty alone. CONCLUSIONS: This study found the risk of mortality to be elevated following angioplasty alone in comparison to revascularization with stent placement, without a corresponding significant difference in iatrogenic stroke rate. This may represent selection bias due to patient characteristics not defined in the database, but it also may indicate that patients with ICAD and acute stroke have increased odds of stenosis that is refractory to angioplasty alone and have a high risk of mortality without revascularization. PMID- 27403217 TI - Auditory Hallucinosis as a Presenting Feature of Interpeduncular Lipoma with Proximal P1 Segment Fenestration: Report of a Rare Case and Review of Literature on Peduncular Hallucinosis. AB - The authors present a unique case of intracranial lipoma in the interpeduncular cistern associated with proximal P1 segment fenestration. This patient is a 20 year-old male with extensive psychiatric history and complaints of recent auditory hallucinations. Cranial magnetic resonance imaging (MRI) (T1, T2, and FLAIR) showed a hyperintense lesion in the left aspect of interpeduncular cistern with a prominent flow void within the hyperintense lesion suggestive of a combined vascular-lipomatous lesion. Computed tomography (CT) angiography showed a high-riding large tortuous P1 segment on the left side with proximal fenestration, the ectatic posteromedial limb harboring a fusiform dilated segment. Since there are anecdotal cases of cerebral aneurysms associated with intracranial lipomas, a conventional angiography was done, which confirmed a proximal left P1 fenestration and a fusiform-dilated segment, and no aneurysm. There are few cases of hallucinations associated with a vascular midbrain pathology reported in literature, but hallucinations associated with a combination of lipoma and arterial ectasia have never been reported. This article not only demonstrates the MRI and angiographic appearance of this rare lipomatous lesion but also highlights this unique association and significance of auditory hallucinations as a clinical presentation, akin to peduncular hallucinosis. PMID- 27403218 TI - Lingual Artery-Retromandibular Vein Fistula Four Years after an Uncomplicated Carotid Endarterectomy: Case Report and Review of Possible Etiologies and Treatment Options. AB - The external carotid artery's lingual branch to retromandibular venous fistula following a carotid endarterectomy has not been reported earlier in literature. We report a unique case of an 87-year-old man who had a right-sided carotid endarterectomy in 2009 and presented four years later with complaints of fullness and discomfort in the area of right parotid gland with associated pulsatile tinnitus. A computed tomography (CT) scan of the neck revealed a deep portion of the right parotid gland having abnormal aneurysmal dilatation of a vascular structure, which appeared to be an arteriovenous fistula between branches of right external carotid artery and the retromandibular vein. Conventional catheter angiogram showed a complex arteriovenous fistula seen with the right retromandibular vein receiving multiple small arterial feeders from the right external carotid artery via its lingual artery branch. Slight reflux was noted into the right pterygoid plexus, right maxillary, and right submental veins as well. Surgical treatment was deferred due to high risk of inadvertent facial nerve injury from extensive parotid dissection involved in the procedure. Transarterial embolization of five discrete arterial branches from the right external carotid artery supplying the fistula was performed using particles with resultant remarkable slowing of the venous drainage into the retromandibular vein. After the procedure, his tinnitus and ear fullness resolved completely. The presence of arteriovenous fistula after carotid endarterectomy is a rare yet serious complication and therefore should be diagnosed early and treated promptly. The article highlights the relevant literature on arteriovenous fistula formation in the setting of arterial patch, intraoperative shunting, and surgical site infections. PMID- 27403219 TI - Acute Bilateral Internal Carotid Occlusion from Embolization of Left Atrial Thrombus During Transesophageal Echocardiography: Case Report. AB - BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) is a relatively safe imaging modality used to visualize intracardiac thrombus. SUMMARY OF CASE: We report on a unique, fatal complication during TEE of embolization of a pre existing "smoking" left atrial thrombus causing acute bilateral internal carotid occlusion, confirmed on angiogram. CONCLUSIONS: Patients with history of lung pathology, such as COPD, who experience retching and cough during transesophageal echocardiography may be more susceptible to embolization of pre-existing thrombi. A need exists to risk stratify such patients. PMID- 27403220 TI - Atrial Fibrillation in Patients with Transient Ischemic Attack in Accordance with the Tissue-Based Definition. AB - BACKGROUND: Transient ischemic attack (TIA) management requires a cardiac evaluation with a Holter electrocardiogram (ECG), preferably a long-term (24 h) electrocardiogram (LT-ECG), to detect atrial fibrillation (AF), which places patients at higher risk of cerebrovascular events. The aim of this study was to determine the frequency of AF using ECG and LT-ECG in patients with tissue-based TIA. METHODS: During a three-year period (starting in 2011), all consecutive patients with tissue-based TIA (no evidence of infarction by brain imaging) were included and prospectively evaluated. RESULTS: Of 861 patients (mean age, 70 +/- 13 years; 49.7% women), 854 patients (99.2%) had an ECG at admission, and 338 patients (39.3%) underwent 24-h LT-ECG monitoring during hospitalization. Patients who underwent LT-ECG monitoring were significantly younger (68 vs. 71 years; P=0.001) and experienced longer symptom duration (143 vs. 79 minutes; P=0.024) compared with those who did not. Furthermore, they had lower rates of unilateral weakness (32% vs. 39%; P=0.034) and previous strokes (18% vs. 26%; P=0.007). The LT-ECG investigation was also associated with longer hospitalization (7.9 vs. 5.7 days; P<0.001). A total of 77 patients (8.9%) exhibited AF on the ECG at admission. The LT-ECG revealed AF among seven patients (2.1%); five of these received a new treatment with oral anticoagulation based on the LT-ECG findings. Using the logistic regression, the presence of AF was associated with the following: age over 65 years (odds ratio [OR], 20.6; 95% confidence interval [CI], 2.8-152; P=0.003), hypertension (OR, 3.1; 95% CI: 1 8.9; P=0.041) and increased glucose level >6.05 mmol/L) on admission (OR, 1.9; 95% CI: 1-3.5; P=0.036). CONCLUSION: Cardiac evaluation with LT-ECG appears to increase the rate of detected AF and may lead to a change in secondary prophylaxis in patients with tissue-based TIA. PMID- 27403222 TI - Study of the Efficacy, Safety and Tolerability of Low-Molecular-Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients with Embolic Stroke due to Atrial Fibrillation. AB - BACKGROUND: Anticoagulation with adjusted dose warfarin is a well-accepted treatment for the prevention of recurrent stroke in patients with atrial fibrillation. Meanwhile, using bridging therapy with heparin or heparinoids before warfarin for initiation of anticoagulation is a matter of debate. We compared safety, efficacy, and tolerability of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as a bridging method in patients with recent ischemic stroke due to atrial fibrillation. METHOD: This study was a randomized single-blind controlled trial in patients with acute ischemic stroke due to atrial fibrillation who were eligible for receiving warfarin and were randomly treated with 60 milligrams (mg) of LMWH (enoxaparin) subcutaneously every 12 h, or 1000 units/h of continuous intravenous heparin. The primary efficacy endpoints were recurrence of new ischemic stroke, myocardial infarction and/or death. The primary safety endpoint was central nervous system and/or systemic bleeding. RESULTS: Seventy-four subjects were recruited. Baseline demographic and clinical characteristics of two groups were matched. Composite endpoint outcome of new ischemic stroke, myocardial infarction, and/or death in follow-up period was seen in 10 subjects (27.03%) in UFH group and in four subjects (10.81%) in LMWH group (p value: 0.136). All hemorrhages and symptomatic central nervous system (CNS) hemorrhages in follow-up period were in 7 (18.9%) and 4 (10.8%) patients in UFH group, in 5 (13.5%), and 3 (8.1%) patients in LMWH group (p values: 0.754 and 0.751), respectively. Drop out and major adverse effects such as heparin-induced thrombocytopenia and drug hypersensitivity were not seen in any patient. CONCLUSION: Enoxaparin can be a safe and efficient alternative for UFH as bridging therapy. PMID- 27403221 TI - Use of Intra-aortic- Balloon Pump Counterpulsation in Patients with Symptomatic Vasospasm Following Subarachnoid Hemorrhage and Neurogenic Stress Cardiomyopathy. AB - INTRODUCTION: Intra-aortic counterpulsation balloon pumps (IABPs) have been widely used to augment hemodynamics in critically ill patients with cardiogenic shock and have recently been proposed as a management strategy for subarachnoid hemorrhage (SAH) patients with neurogenic stress cardiomyopathy (NSC). Prior case series have described the use of IABP as a means to manage cardiogenic shock in this patient population; however, we sought to describe our experience with IABP as a means to wean vasopressor requirement while augmenting hemodynamics and maintaining pressures at goal. METHODS: Five patients were identified from a single center, prospective, observational cohort study that received an IABP for the management of ischemia related to cerebral vasospasm in the setting of NSC. We evaluated all cases for efficacy of IABP in reducing vasopressor requirement, and complications. RESULTS: Vasopressor requirements were reduced by a mean of 50% (range 25-65%) following IABPs placement within 24-48 h. There were no significant complications from IABPs. Out of the five patients, the outcome in three cases was favorable (mRS<=1). Two patients suffered delayed cerebral ischemia (DCI), one patient passed away due to severe sepsis, and one patient was left with severe disability. Only one patient required anticoagulation and that was for a preexisting deep venous thrombosis. CONCLUSION: The use of IABPs may be beneficial as an adjunctive therapy in SAH patients with concomitant symptomatic vasospasm and NSC. PMID- 27403223 TI - Syncope in Patient with Bilateral Severe Internal Carotid Arteries Stenosis/Near Occlusion: A Case Report and Literature Review. AB - BACKGROUND: Syncope is commonly worked up for carotid stenosis, but only rarely attributed to it. Considering paucity of such cases in literature, we report a case and discuss the pathophysiology. DESIGN/METHODS: We report a patient with high-grade bilateral severe internal carotid artery (ICA) stenosis who presented with syncopal episodes in the absence of stroke, orthostatic hypotension, significant cardiovascular disease, or vasovagal etiology. We reviewed all literature pertaining to syncope secondary to carotid stenosis and other cerebrovascular disease. RESULTS: A 67-year-old man presented with two brief syncopal episodes. History and physical examination was not suggestive of seizure or vasovagal syncope. Other workup was negative for any stroke or syncope secondary to cardiac or vasovagal etiology. Magnetic resonance angiography (MRA) revealed bilateral ICA severe stenosis. This was confirmed by transfemoral carotid vessels angiography. Internal carotid angioplasty and stenting was performed on one side. After this, the patient remained asymptomatic. After one month, carotid endarterectomy (CEA) of contralateral side was performed. Patient remained symptom free after that. On review of literature, we identified only 12 cases of syncope attributable to carotid stenosis and reviewed 24 cases attributable to other cerebrovascular disease. CONCLUSION: Syncope secondary to carotid stenosis, especially in the absence of any focal ischemic events is rare. It can only be expected in those patients who have bilateral hemodynamically significant carotid disease, which is unlikely in the absence of any focal ischemic events. PMID- 27403224 TI - Small Intracranial Aneurysm Treatment Using Target ((r)) Ultrasoft (TM) Coils. AB - PURPOSE: The introduction of small, soft, complex-shaped microcoils has helped facilitate the endovascular treatment of small intracranial aneurysms (IAs) over the last several years. Here, we evaluate the initial safety and efficacy of treating small IAs using only Target((r)) Ultrasoft(TM) coils. MATERIALS AND METHODS: A retrospective review of a prospectively maintained clinical database at a single, high volume, teaching hospital was performed from September 2011 to May 2015. IAs smaller than or equal to 5.0 mm in maximal dimension treated with only Target((r)) Ultrasoft(TM) coils were included. RESULTS: A total of 50 patients with 50 intracranial aneurysms were included. Subarachnoid hemorrhage from index aneurysm rupture was the indication for treatment in 23 of 50 (46%) cases, and prior subarachnoid hemorrhage (SAH) from another aneurysm was the indication for treatment in eight of 50 (16%) cases. The complete aneurysm occlusion rate was 70% (35/50), the minimal residual aneurysm rate was 14% (7/50), and residual aneurysm rate was 16% (8/50). One intraoperative aneurysm rupture occurred. Three patients died during hospitalization from clinical sequelae of subarachnoid hemorrhage. Follow-up at a mean of 13.6 months demonstrated complete aneurysm occlusion in 75% (30/40) of cases, near complete occlusion in 15% (6/40) of cases, and residual aneurysm in 10% (4/40) of cases, all four of which were retreated. CONCLUSION: Our initial results using only Target((r)) Ultrasoft(TM) coils for the endovascular treatment of small intracranial aneurysms demonstrate initial excellent safety and efficacy profiles. PMID- 27403225 TI - Multiparametric Approach Enhances Detection of Patients with Cerebral TIAs at Risk of Stroke: A Prospective Pilot Case Series. AB - BACKGROUND: Patients with transient ischemic attack (TIA) are generally clinically unstable, with fear of developing a handicapping stroke. Identification of those at highest and lowest risk of stroke in the first days and weeks after a TIA would allow appropriate use of worthy secondary prevention strategies. OBJECTIVE: Incorporation of a clinical scoring system, neurovascular imaging, and magnetic resonance-diffusion-weighted imaging (MR-DWI) to help predicting risk of developing an ischemic stroke following a TIA. SUBJECTS AND METHODS: A prospective observational study was conducted on 25 patients with TIAs, 64% were females, and 26% were males, with a mean age of 57+/-10.36. Patients were assessed clinically and an ABCD(2) score was applied. Patients have undergone diffusion-weighted imaging (DWI), within 24 h from the event, and intra and extracranial duplex study. Patients were followed up at intervals of one week, three months, six months, and one year. RESULTS: Six patients (24%) developed stroke on their follow-up, most of them (83.3%) had their strokes within the first three months and had an initial ABCD(2) score of >=4. The development of stroke was associated with the presence of significant extra and/or intracranial vessel disease (P=0.006) and the presence of acute lesions on their DWI (P=0.035). CONCLUSION: Incorporation of brain MR-DWIs and neurovascular imaging together with the ABCD(2) score improves prediction of ischemic stroke following TIA. PMID- 27403226 TI - Ultrasound-Guided Second Trimester Fetal Electroencephalography in Two Pregnant Volunteers: A Technical Note. AB - BACKGROUND AND PURPOSE: Data from electroencephalography (EEG) in preterm infants and neonates suggest that electroencephalographic abnormalities are likely present during antepartum period or fetal stage. We describe our initial effort to record fetal EEG with emphasis on technical aspects since such technique has not been developed as a viable and reproducible method. METHODS: The fetal heads were located in two pregnant volunteers (29 years old and 26 years old) with 28 weeks of gestation by ultrasound imaging. Four surface electrodes were placed on maternal abdominal surface approximately 5 cm anterior to the lateral aspect of fetal head as confirmed by acoustic shadowing of the electrodes on ultrasound. A second set of recordings were performed in first volunteer with four electrodes placed on the maternal abdominal surface in front of the uterus distant to fetal head. RESULTS: The analysis in the first volunteer demonstrated that the activity consisted of mixture of theta (4-7 Hz) and delta (1-4 Hz) waves which formed approximately 70% and 30% of the background rhythm. The analysis in the second volunteer demonstrated that the activity consisted of mixture of theta and delta, which formed approximately 30% and 70% of the background rhythm. There was superimposed beta (13-30 Hz) and infrequently gamma (30-100 Hz) activity. Maternal electrocardiographic QRS complex and respiratory artifacts were seen in some leads. During second recording, the electrodes distant to fetal head recorded predominantly delta with lesser proportion of theta waves. CONCLUSIONS: We report our initial experience in acquisition of fetal EEG. The findings reported here will help to guide further research into developing methodologies for the performance of fetal EEG. PMID- 27403227 TI - Cerebral Venous Engorgement in Hydrops Fetalis. PMID- 27403228 TI - Erratum. AB - [This corrects the article on p. 68 in vol. 8, PMID: 26301035.][This corrects the article on p. 37 in vol. 8.]. PMID- 27403229 TI - Oxidative Stress Related Diseases in Newborns. AB - We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID- 27403230 TI - Biofunctional Activities of Equisetum ramosissimum Extract: Protective Effects against Oxidation, Melanoma, and Melanogenesis. AB - Equisetum ramosissimum, a genus of Equisetaceae, is a medicinal plant that can be separated into ethyl acetate (EA), dichloromethane (DM), n-hexane (Hex), methanol (MeOH), and water extracts. EA extract was known to have potent antioxidative properties, reducing power, DPPH scavenging activity, and metal ion chelating activity. This study compared these five extracts in terms of their inhibiting effects on three human malignant melanomas: A375, A375.S2, and A2058. MTT assay presented the notion that both EA and DM extracts inhibited melanoma growth but did not affect the viabilities of normal dermal keratinocytes (HaCaT) or fibroblasts. Western blot analyses showed that both EA and DM extracts induced overexpression of caspase proteins in all three melanomas. To determine their roles in melanogenesis, this study analyzed their in vitro suppressive effects on mushroom tyrosinase. All extracts except for water revealed moderate suppressive effects. None of the extracts affected B16-F10 cells proliferation. EA extract inhibited cellular melanin production whereas DM extract unexpectedly enhanced cellular pigmentation in B16-F10 cells. Data for modulations of microphthalmia associated transcription factor, tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 showed that EA extract inhibited protein expression mentioned above whereas DM extract had the opposite effect. Overall, the experiments indicated that the biofunctional activities of EA extract contained in food and cosmetics protect against oxidation, melanoma, and melanin production. PMID- 27403231 TI - Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury. AB - Background and Aims. Human embryonic stem cell- (hESC-) derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP) in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days) and then on more differentiated cardiomyocytes (6 + 24 days), both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N acetylpenicillamine (SNAP) (10(-7), 10(-6), and 10(-5) M), BNP (10(-9), 10(-8), and 10(-7) M), and the nonspecific NO synthase inhibitor Nomega-nitro-L-arginine (L-NNA, 10(-5) M). Results. SNAP (10(-6), 10(-5) M) significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10(-6) M) also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms. PMID- 27403234 TI - Professional Self-Regulation for Nursing and Midwifery in Oman: Protecting the Public and Enhancing the Quality of Care. PMID- 27403233 TI - DISJUNCTIVE NORMAL SHAPE MODELS. AB - A novel implicit parametric shape model is proposed for segmentation and analysis of medical images. Functions representing the shape of an object can be approximated as a union of N polytopes. Each polytope is obtained by the intersection of M half-spaces. The shape function can be approximated as a disjunction of conjunctions, using the disjunctive normal form. The shape model is initialized using seed points defined by the user. We define a cost function based on the Chan-Vese energy functional. The model is differentiable, hence, gradient based optimization algorithms are used to find the model parameters. PMID- 27403235 TI - The Practice of Ethnomedicine in the Northern and Southern Provinces of Oman. AB - Studies related to ethnomedicines investigate the way people manage illness and diseases because of their cultural perspective. Fields like ecology, epidemiology, and medical history jointly contribute to the broad field of ethnomedical study. The knowledge gathered by traditional healers in the villages and tribal communities on natural medicines remains unfamiliar to the majority of scientists and the general population. The study of ethnomedicine principally involves the compilation of empirical data, particularly the patterns of illness and treatments from folklore. Due to deforestation, and urbanization of the desert jungles, many valuable medicinal plants present in the study areas appear to be facing extinction in the near future if no proper conservation plans are carried out. This survey documented 33 different herbs used by the natives of Oman for various ailments. Parts of a particular plant, fresh or dried, might be crushed and drunk as an infusion or used externally as a poultice, ground into a paste, or inhaled as smoke. The survey identified 22 plant families, and 18 traditional treatment groups. PMID- 27403232 TI - Current Antioxidant Treatments in Organ Transplantation. AB - Oxidative stress is one of the key mechanisms affecting the outcome throughout the course of organ transplantation. It is widely believed that the redox balance is dysregulated during ischemia and reperfusion (I/R) and causes subsequent oxidative injury, resulting from the formation of reactive oxygen species (ROS). Moreover, in order to alleviate organ shortage, increasing number of grafts is retrieved from fatty, older, and even non-heart-beating donors that are particularly vulnerable to the accumulation of ROS. To improve the viability of grafts and reduce the risk of posttransplant dysfunction, a large number of studies have been done focusing on the antioxidant treatments for the purpose of maintaining the redox balance and thereby protecting the grafts. This review provides an overview of these emerging antioxidant treatments, targeting donor, graft preservation, and recipient as well. PMID- 27403236 TI - Transfusion Consent in Oman: Physicians' Perception at a Tertiary Care University Hospital. AB - OBJECTIVES: Transfusion is a common intervention that mandates the discussion of benefits, risks, and alternatives to planned transfusions. In Oman, transfusion consent was first introduced at the Sultan Qaboos University Hospital in March 2014. We sought to evaluate our physicians' opinions, attitudes, and perception of the transfusion consent process. METHODS: Attending physicians of different specialties were invited to complete an anonymous survey on transfusion consent. RESULTS: A total of 114 physicians responded to the survey. Transfusion benefits and risks were explained regularly by 91% and 87% of the surveyed physicians, respectively. On the other hand, alternatives were declared by only 38%. Discomfort with the consent process was admitted by 10% of the physicians. There was no statistically significant association between discomfort in obtaining the consent and the physician seniority (p = 0.801), nor their specialties (p = 0.623). The importance of the consent process was acknowledged by 80% of surveyed physicians, who supported its implementation in other hospitals. CONCLUSION: This survey reflects positive attitudes of the surveyed physicians on the importance of transfusion consent. However, actions are required to achieve physicians' full ease with the process and to ensure that transfusion alternatives are discussed. We advocate implementation of transfusion consent in other hospitals in Oman. PMID- 27403237 TI - Psychiatric Disorders in Children and Adolescents Attending Pediatric Out Patient Departments of Tertiary Hospitals. AB - OBJECTIVES: Psychiatric disorders are increasingly recognized among children and adolescents in Bangladesh. Psychiatric disorders are more common in children with chronic and acute pediatric disorders. Our study was designed to determine the psychiatric disorders among children and adolescents attending pediatric outpatient departments of tertiary care hospitals. METHODS: This cross-sectional study was carried out from July 2012 to February 2013 in pediatric outpatient departments of three prime tertiary level hospitals of Dhaka, Bangladesh. A purposive sampling technique was used. A total of 240 male and female children aged 5 to 16 years old were included in the study. We used a semi-structured questionnaire to obtain sociodemographic and other relevant clinical information about the children and their families from their parents or caregivers and a validated parent version of the Bangla Development and Well-Being Assessment (DAWBA) for measuring psychopathology. RESULTS: The mean age of the children was 9.0+/- 2.6 years. The majority (71%) of children were in the 5-10 year age group. The male/female ratio was 1.2:1. Among the respondents, 18% were found to have a psychiatric disorder. Behavioral disorders, emotional disorders, and developmental disorders were found in 9.0%, 15.0% and 0.4% respectively. Hyperkinetic disorder was the single most frequent (5.0%) psychiatric disorder. CONCLUSIONS: A significant number of children were found to have psychiatric disorders. Our study indicates the importance of identification and subsequent management of psychiatric conditions among the pediatric population. PMID- 27403238 TI - Silibinin Improves the Effects of Methotrexate in Patients with Active Rheumatoid Arthritis: Pilot Clinical Study. AB - OBJECTIVES: Our study sought to evaluate the effects of silibinin in patients with active rheumatoid arthritis (RA) treated with methotrexate (MTX). METHODS: We conducted a randomized multi-center, double-blind, placebo-controlled clinical trial over a 16-week treatment period at the Al-Sader and Baghdad Teaching Hospitals in Najaf and Baghdad, respectively. A total of 60 patients (30 of each sex) with active RA, already maintained on 12 mg MTX weekly for at least three consecutive months, were included in the study. Patients were randomly allocated to receive either 120 mg silibinin twice daily or a placebo, combined with their regular MTX regimen. The patients were evaluated by measuring disease activity score using the 28-joint Disease Activity Score, Simple Disease Activity Index, and Health Assessment Questionnaire-Disability Index scores at the start and end of the study. Blood samples were evaluated for the erythrocyte sedimentation rate (ESR), hemoglobin (Hb), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK), anti-cyclic citrullinated peptide (CCP), and the serum cytokine levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, IL-10, and IL-2. RESULTS: Silibinin significantly decreases the already elevated clinical scores compared to placebo treatment. ESR, IL-8, IL-6, TNF-alpha, anti-CCP, hs CRP levels were significantly reduced. Additionally, the use of silibinin significantly increases Hb, IL-10, and IL-2 levels. CONCLUSION: Silibinin may improve the effects of MTX on certain biochemical and clinical markers of patients with active RA. PMID- 27403239 TI - Prevalence of Metabolic Syndrome in Patients with Schizophrenia Referred to Farabi Hospital, Kermanshah, Iran. AB - OBJECTIVES: Our study was conducted to determine the prevalence of metabolic syndrome in patients with schizophrenia. METHODS: The study population included all patients with schizophrenia who were referred to Farabi Hospital, Kermanshah, Iran, between March 2014 and March 2015. A total of 280 subjects who met the study criteria were selected according to the census sampling method. RESULTS: The prevalence of metabolic syndrome was 30.4% (20.7% in men and 51.5% in women). The prevalence of metabolic syndrome was greater in patients > 40 years than patients aged 20-40 years. There was a significant relationship between marital status and number of hospitalizations with the prevalence of metabolic syndrome. CONCLUSIONS: Given the high prevalence of metabolic syndrome in patients with schizophrenia, healthcare professionals should take measures to identify the risk factors and timely treatment of affected patients, thereby improving the patient's quality of life and reducing health costs. PMID- 27403240 TI - Presentation, Management, and Outcome of Thyroglossal Duct Cysts in Adult and Pediatric Populations: A 14-Year Single Center Experience. AB - OBJECTIVES: A thyroglossal duct cyst (TDC) is a frequent congenital midline anomaly of the neck that usually manifests during the first decade of life. We aimed to describe the presentation, management, and outcome of TDC in pediatric and adult cases. METHODS: A retrospective observational analysis was conducted for all patients diagnosed and treated for TDC between 2000 and 2014 in a single center in Qatar. Data included patients' demographics, presentations, preoperative investigations, anesthesia type, histopathological findings, surgical management, recurrences, and complications. RESULTS: We identified 102 patients, of which 57% were males. The mean age of patients was 20.2+/-15.6 years. A bimodal distribution of TDC has been observed, which peaked between the ages of 6-13 years and at >=19 years. The preoperative evaluation mainly includes ultrasonography (66%), thyroid function test (44%), and fine-needle aspiration cytology (10%). The median size of the cyst was 25 (2-60) mm. Patients mainly presented with an asymptomatic midline neck mass at or below the hyoid bone (82%), followed by fistula (9%), infection (2%), and dysphagia (2%). Eighty-nine cases were identified preoperatively as TDC. The histopathological findings confirmed TDC with hyoid bone in 61 cases, and TDC alone in 38 cases. Eighty patients underwent the Sistrunk procedure while excision of TDC alone was observed in 18 cases. Five cases of recurrent disease were also treated. Adults had a greater median cyst size (30 (9-60) vs. 22 (2-55) mm; p = 0.005) and required prolonged operation time (69 (1-169) vs. 32.5 (1-140) mins; ?p = 0.004) compared to the pediatric group. CONCLUSION: The occurrence of TDC shows a bimodal age distribution. Preoperative evaluation and time for surgery vary whereas clinical presentations, surgical management, and postoperative outcomes are comparable among adult and pediatric groups. Ultrasonography is the preferred diagnostic modality, and the Sistrunk procedure remains the primary choice of treatment. PMID- 27403241 TI - Attitudes of Patients in Developing Countries Toward Participating in Clinical Trials: A Survey of Saudi Patients Attending Primary Health Care Services. AB - OBJECTIVES: Clinical trials are experimental projects that include patients as subjects. A number of benefits are directly associated with clinical trials. Healthcare processes and outcomes can be improved with the help of clinical trials. This study aimed to assess the attitudes and beliefs of patients about their contribution to and enrolment in clinical trials. METHODS: A cross sectional study design was used for data collection and analysis. A questionnaire was developed with six categories to derive effective outcomes. RESULTS: Of the 2000 participants approached to take part in the study, 1081 agreed. The majority of the study population was female, well educated, and unaware of clinical trials. Only 324 subjects (30.0%) had previously agreed to participate in a clinical trial. The majority (87.1%) were motivated to participate in clinical trials due to religious aspects. However, fear of any risk was the principal reason (79.8%) that reduced their motivation to participate. CONCLUSIONS: The results of this study revealed that patients in Saudi Arabia have a low awareness and are less willing to participate in clinical trials. Different motivational factors and awareness programs can be used to increase patient participation in the future. PMID- 27403242 TI - Pandemic Influenza A H1N1 in Oman: Epidemiology, Clinical Features, and Outcome of Patients Admitted to Sultan Qaboos University Hospital in 2009. AB - OBJECTIVES: Oman experienced the H1N1 pandemic in 2009 that initially started in Mexico and the United States. We present the epidemiology, clinical features, and outcome of cases admitted to Sultan Qaboos University Hospital. METHODS: We retrospectively reviewed all patients admitted with confirmed influenza A H1N1 infection from August to December 2009. The study included adults and pediatric patients. We looked at the clinical and laboratory factors associated with increased length of hospital stay. RESULTS: There were 68 patients admitted with influenza A H1N1 infection, and their median age was 23 years. The most common symptoms were fever (100%) and cough (79.4%). The most common reason for admission was the severity of illness (69.1%). Lymphopenia was the most common hematological abnormality (41.8%). All patients received treatment with oseltamivir. One patient died secondary to multi-organ failure. On multivariate analysis, severity of illness, use of steroids, anemia, lymphopenia, and abnormal alanine amino transferase levels were associated with increased length of stay. CONCLUSIONS: The H1N1 pandemic in Oman followed the international trends in terms of clinical presentation and laboratory values for patients admitted to the hospital. PMID- 27403243 TI - Latent Tuberculosis in Health Care Workers Exposed to Active Tuberculosis in a Tertiary Care Hospital in Oman. AB - OBJECTIVES: Data on the prevalence of tuberculosis (TB) in healthcare workers (HCW) in Oman and the Arabian Gulf is scarce. The aim of this study was to estimate the prevalence of latent tuberculosis (LTB) among HCW exposed to active TB in one of the tertiary care hospitals in Muscat. METHODS: Exposed HCW were screened for LTB from January to June 2012 using skin tuberculin and serum interferon tests. Candidates were followed-up for a total of nine months. Descriptive statistics were used to summarize the data. RESULTS: A total of 371 exposed HCW were involved in the study. The incidence of LTB in exposed HCW was 33.2% (n = 123). Almost 54% (66/123) of the HCW started treatment and only 42.4% (28/66) completed the full nine-month treatment course. CONCLUSIONS: The high prevalence of LTBI in exposed HCW merits further evaluation of the screening and treatment programs in the country. Future countrywide studies are warranted to provide more precise statistics on the prevalence and management of this public health issue. PMID- 27403244 TI - Refractory Seizure in Childhood: Dyke-Davidoff-Masson Syndrome Revisited. AB - Dyke-Davidoff-Masson syndrome (DDMS) is a rare disorder characterized by recurrent seizures, facial asymmetry, contralateral hemiplegia, radiologic features of cerebral hemiatrophy, and ipsilateral compensatory hypertrophy of the skull bone and sinuses. We describe three cases of children with DDMS, who initially presented with refractory seizure to the pediatric department of North Bengal Medical College and Hospital, India. In each case, the clinical features noted along with computed tomography or magnetic resonance imaging helped confirm the diagnosis of DDMS. DDMS should be considered as a differential diagnosis of refractory seizures in children. We seek to emphasize the importance of thorough clinical and neuroimaging workup of seizure disorder in children for the proper management of the condition. PMID- 27403245 TI - Neuroleptic Malignant Syndrome Associated with Lithium Toxicity. AB - Neuroleptic Malignant Syndrome (NMS) is an idiosyncratic and potentially life threatening reaction to neuroleptic drugs. Lithium is a first-line mood stabilizer used in the treatment and prophylaxis of bipolar disorder. There are several case reports of lithium-associated NMS, but only when it was given in combination with antipsychotics. Therefore, the possibility of NMS being secondary to the antipsychotics could not be ruled out in those cases. Here we present a case of lithium-induced NMS in a patient who was not being treated concomitantly with any other agent known to cause NMS. The patient, a 74-year-old female with a 30-year history of bipolar affective disorder, was admitted to the emergency room of the All India Institute of Medical Sciences, New Delhi, with history of high fever and generalized weakness for 10 days before the admission. NMS was established based the presence of three cardinal symptoms. She was started on intravenous fluids to correct her sodium levels slowly and requested to follow-up at the psychiatry clinic. PMID- 27403246 TI - Fibrosarcoma of the Gingiva: An Unusual Presentation. AB - Fibrosarcoma is a malignant tumor of the fibroblasts, which is liable to recur and metastasize, most frequently in the lungs. Although fibrosarcomas are rare, they can occur anywhere in the body. The most common sites are in the retroperitoneum, thigh, knee, and distal extremities. It is very uncommon in the head and neck region and comprises only about 1% of all the malignancies in humans. Almost 23% are seen in the oral cavity. The prognosis for fibrosarcomas is poor with a five-year survival rate of 20-35%. The common modality of treatment is radical surgery. We report a rare presentation of gingival fibrosarcoma in a young female, who presented with a painless lump. PMID- 27403247 TI - The Adverse Events, Signs, and Management of Neonatal Bacillus Calmette-Guerin Vaccine Overdose. AB - A two-day-old male neonate was inadvertently immunized with 20-times the recommended dose of Bacillus Calmette-Guerin (BCG) vaccine (1.0 ml instead of 0.05 ml). Examination of the neonate after one day revealed no signs of local reaction at the site of injection or systemic manifestation. However, nine days later, he developed a swelling (4 * 3 cm) at the site of injection without any enlargement of the lymph node, pallor, or jaundice. A needle aspiration of the swelling was done and sent for culture. The culture showed the BCG strain only. The infant was not started on antituberculosis medication, due to the absence of symptoms suggestive of systemic disease. There were no other complications up to the age of 18 months. The case highlights the importance of administering the correct dose and using the appropriate technique of the BCG vaccine, and explains the management options to prevent local and systematic complications that may occur due to overdose. PMID- 27403248 TI - Evaluation of Risk Factors for Intravenous Colistin Use-related Nephrotoxicity. AB - OBJECTIVES: We investigated the incidence of and risk factors for nephrotoxicity in patients using intravenous colistin. METHODS: This retrospective, observational study was conducted at Karadeniz Technical University, Faculty of Medicine, clinics and intensive care unit between 1 January 2009 and 1 January 2013. Intravenous colistin was administered to 133 patients at a dose of 2.5-5.0 mg/kg/day. RESULTS: The patients mean age was 54.3+/-19.1 years and the mean duration of treatment was 13.5+/-3.6 days. Nephrotoxicity developed in 5.0+/-2.8 days in 38 (28.6%) patients. Based on RIFLE (risk, injury, failure, loss of kidney function, and end-stage kidney disease) criteria, 15 (39.5%) patients were class 1, 17 (44.7%) were class 2, six (15.8%) were class 3, and none were class 4. The mean duration of development of nephrotoxicity was 5.0+/-2.8 days. Hemodialysis requirement was observed in two (5.2%) of the 38 patients who developed nephrotoxicity. In these cases, colistin therapy was not discontinued. Nephrotoxicity was correlated with advanced age, high pretreatment serum creatinine levels, diabetes mellitus, and chronic obstructive pulmonary disease. CONCLUSIONS: The use of colistin is relatively safe for patients that have normal renal functions. However, better standardization of the definition of nephrotoxicity in those patients with the use of scoring systems and close monitoring are necessary. PMID- 27403249 TI - Complex Mass. PMID- 27403250 TI - The Association of Neck Circumference and Obesity: That Is Not All Yet. PMID- 27403252 TI - Hypothermic activity of acetaminophen; involvement of GABAA receptor, theoretical and experimental studies. AB - OBJECTIVES: The mechanism of hypothermia action of acetaminophen (APAP) remains unclear even 125 years after its synthesis. Acetaminophen produces hypothermia. The mechanism of this reduction in core body temperature is not clear but evidence shows that it is not dependent on opioid and cannabinoid receptors. Because of strong documents about the roles of GABA and benzodiazepine receptors in hypothemic activity of some drugs such as diazepam, we determined if these receptors also contributes to the hypothermic effect of APAP. MATERIALS AND METHODS: Diazepam (5 mg/kg, IP) was used for induction of hypothermia. Flumazenil (10 mg/kg, IP) or picrotoxin (2 mg/kg, IP) used for reversal of this effect. Rats injected with APAP (100, 200 or 300 mg/kg, IP). Baseline temperature measurements were taken with a digital thermometer via rectum. To evaluate the structural correlation between APAP and benzodiazepine receptor ligands, numerous models are selected and studied at HF/6-31G* level of theory. Relative energies, enthalpies and Gibbs free energies were calculated for all selected drugs. RESULTS: Diazepam induced hypothermia was reversed by flumazenil or picrotoxin. Rats injected with APAP displayed dose- and time-related hypothermia. For combined administration, the hypothermic effect of APAP (200 mg/kg) was strongly reduced by pretreatment with picrotoxin or flumazenil P<0.0001and P<0.01, respectively. Selective structural data, bond length, dihedral angles, and related distance in pharmacophore of APAP and BZDR models were the same. Some significant structural analogues were obtained between these drugs. CONCLUSION: Results suggest hypothermic action of acetaminophen may be mediate by its effect at GABAA benzodiazepine receptor. PMID- 27403251 TI - Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review. AB - Saffron, the dried red-orange stigmas of Crocus sativus L, has been known as a flavoring agent, food coloring and traditional herbal medicine. Pharmacological effects of saffron are mainly attributed to crocin, crocetin, picrocrocin and safranal. These components especially crocin, have significant effects including antidepressant and anticonvulsant, analgesic, anti-cancer and other therapeutic effects on different parts of our body namely cardiovascular, immune, respiratory, genital-urinary and central nervous system. According to the reports and findings, saffron plays a key role to cure different digestive system disorders via chemopreventive, inhibition of cell proliferation, induction of apoptosis, antioxidant effects and radical scavenging, genoprotective property, prevention of lipid peroxidation and anti-inflammatory processes. The outcome of the above mentioned mechanisms shows potential therapeutic properties of saffron against liver cancer, hepatotoxicity, fatty liver, hyperlipidemia, stomach cancer, peptic ulcer, colon cancer, ulcerative colitis, diabetes and pancreas cancer and ileum contractions. According to global statistics, the susceptibility to intestinal diseases is considered as a significant matter and can be important in health planning in any community. Several strategies for treatment and prevention of the digestive system diseases have provided that the use of herbal remedies seems effective and useful. Considering the available findings, the present study aims to introduce saffron as a prophylactic and therapeutic agent against gastrointestinal tract disorders. However, further clinical studies seem necessary in various aspects of saffron effects in different parts of body to verify these findings. PMID- 27403253 TI - Feature selection using genetic algorithm for breast cancer diagnosis: experiment on three different datasets. AB - OBJECTIVES: This study addresses feature selection for breast cancer diagnosis. The present process uses a wrapper approach using GA-based on feature selection and PS-classifier. The results of experiment show that the proposed model is comparable to the other models on Wisconsin breast cancer datasets. MATERIALS AND METHODS: To evaluate effectiveness of proposed feature selection method, we employed three different classifiers artificial neural network (ANN) and PS classifier and genetic algorithm based classifier (GA-classifier) on Wisconsin breast cancer datasets include Wisconsin breast cancer dataset (WBC), Wisconsin diagnosis breast cancer (WDBC), and Wisconsin prognosis breast cancer (WPBC). RESULTS: For WBC dataset, it is observed that feature selection improved the accuracy of all classifiers expect of ANN and the best accuracy with feature selection achieved by PS-classifier. For WDBC and WPBC, results show feature selection improved accuracy of all three classifiers and the best accuracy with feature selection achieved by ANN. Also specificity and sensitivity improved after feature selection. CONCLUSION: The results show that feature selection can improve accuracy, specificity and sensitivity of classifiers. Result of this study is comparable with the other studies on Wisconsin breast cancer datasets. PMID- 27403254 TI - The protective effects of epigallocatechin gallate on lipopolysa ccharide-induced hepatotoxicity: an in vitro study on Hep3B cells. AB - OBJECTIVES: In the present study, our aim was to investigate the possible protective effects of epigallocatechin gallate (EGCG) on lipopolysaccharide (LPS) induced hepatotoxicity by using Hep3B human hepatoma cells. Specifically, the study examines the role of some proinflammatory markers and oxidative damage as possible mechanisms of LPS-associated cytotoxicity. Consequently, the hepatocellular carcinoma cell line Hep3B was chosen as a model for investigation of LPS toxicity and the effect of EGCG on LPS-exposed cells. MATERIALS AND METHODS: The Hep3B human hepatoma cells were used for this study. The cytotoxic effects of chemicals (EGCG and LPS), AST and ALT levels, SOD and CAT activities, GSH-Px level and TNF-alpha and IL-6 levels were detected by using different biochemical and molecular methods. LPS and EGCG were applied to cells at various times and doses. RESULTS: The highest treatment dose of EGCG (400 uM) led to a dramatic decrease in SOD level and increase in CAT and GSH levels. Additionally, the highest dose of EGCG also led to a dramatic increase in TNF-alpha and IL-6 levels. On the other hand, effective doses of EGCG (200 and 100 uM) normalized all related parameters levels. CONCLUSION: LPS caused hepatotoxicity, but interestingly, a high dose of EGCG was found to be a cytotoxic agent in this study. However, other two doses of EGCG led to a decrease in both inflammatory cytokine levels and antioxidant enzyme levels. Further studies should examine the effect of EGCG on secondary cellular signaling pathways. PMID- 27403255 TI - Effect of WR-1065 on 6-hydroxydopamine-induced catalepsy and IL-6 level in rats. AB - OBJECTIVES: Neuroinflammation and oxidative stress play a key role in pathogenesis of Parkinson's disease (PD). In the present study we investigated the effect of reactive oxygen species (ROS) scavenger WR-1065 on catalepsy and cerebrospinal fluid (CSF) level of interleukin 6(IL-6) and striatum superoxide dismutase (SOD) activity in 6-hydroxydopamine (6-OHDA) induced experimental model of PD. MATERIALS AND METHODS: Seventy two male Wistar rats were divided into 9 equal groups and 6-OHDA (8 MUg/2 MUl/rat) was infused unilaterally into substantia nigra pars copmacta (SNc) to induce PD. Catalepsy was measured by standard bar test, CSF level of IL-6 was assessed by enzyme-linked immunosorbent assay (ELISA) method and SOD activity measured by spectrophotometric method. In pre-treatment groups WR-1065 (20, 40 and 80 MUg/2 MUl/rat/day, for 3 days) was infused into the SNc before 6-OHDA administration and 21 days later, as a recovery period, behavioral and molecular assay tests were done. RESULTS: Our results showed that pre-treatment with WR-1065 improved (P<0.001) 6-OHDA-induced catalepsy in a dose dependent manner. In 6-OHDA-lesioned animals SOD activity in SNc and CSF level of IL-6 was decreased markedly (P<0.001) when compared with non lesioned group, while pre-treatment with WR-1065(P<0.001) restored their levels up to the normal range. CONCLUSION: Our study indicated that pre-treatment with WR-1065 could modulate catalepsy and IL-6 level in 6-OHDA-lesioned rats. Also WR1065 could increase SOD activity up to normal range. It can be regarded as an anti-oxidative drug in prevention or adjunctive therapy of PD. PMID- 27403256 TI - Intermittent hypoxia reduces microglia proliferation and induces DNA damage in vitro. AB - OBJECTIVES: Intermittent hypoxia (IH), caused by obstructive sleep apnea (OSA), could cause hippocampus or neuron damage through multiple signaling pathways, while the underlying mechanisms are still unclear. Thus, the present study aimed to explore the effect of IH on the biological functions of microglia cells. MATERIALS AND METHODS: Cell proliferation of BV2 cells after exposure to IH were observed by MTT assay and then DNA damage was detected by comet assay. RNA sequencing assay was performed in cells under IH condition and normal conditions to find out the differentially expressed genes, which were further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot assay. RESULTS: As results, IH inhibited the proliferation of BV2 cells, as well as caused DNA damage. RNA-sequencing assay revealed 4 differentially expressed genes (p21, Cyclin D1, Cyclin E2, and Gadd45alpha) which were associated with the network of P53 signaling pathways in BV2 cells, among which, p21 and Gadd45alpha were dramatically increased while Cyclin D1 and Cyclin E2 were both decreased significantly. Moreover, inflammatory factors including IL-6, TNF-alpha and iNOS were significantly up-regulated in microglia cells under IH conditions for 8 hr. CONCLUSION: Our results indicated that IH could inhibit cyclin D1 and cyclin E2 expression via initiating multiple P53 pathways, which further blocked cell cycle transition and attenuated proliferative capability of BV2 cells. Meanwhile, IH activated inflammation reactions in BV2 cells. Present study elaborate the effects of IH on biological functions of microglia and provide theoretical foundation for further study on new therapy methods for OSA. PMID- 27403257 TI - Protective effects of fractions from Artemisia biennis hydro-ethanolic extract against doxorubicin-induced oxidative stress and apoptosis in PC12 cells. AB - OBJECTIVES: This study was designed to indicate whether different fractions from Artemisia biennis hydroethanolic extract could provide cytoprotection against oxidative stress and apoptosis induced by doxorubicin (DOX) in rat pheochromocytoma cell line (PC12). MATERIAL AND METHODS: Cell viability was determined by MTT assay. Also, activation of caspase-3 and superoxide dismutase were evaluated by spectrophotometry. Detection of reactive oxygen species (ROS) and measurement of mitochondrial membrane potential (MMP) were performed by flowcytometry. RESULTS: Treatment of PC12 cells with DOX reduced viability dose dependently. For evaluation of the effect of fractions (A-G) on DOX-induced cytotoxicity, PC12 cells were pretreated for 24 hr with the A. biennis fractions and then cells were treated with DOX. The fractions C and D increased PC12 cells viability significantly compared to DOX treated cells. Moreover, pretreatment with fractions C and D for 24 hr attenuated DOX-mediated apoptosis and the anti apoptotic action of A. biennis fractions was partially dependent on inhibition of caspase 3 activity and also increasing the mitochondrial membrane potential (MMP). Selected A. biennis fractions also suppressed the generation of ROS and increased superoxide dismutase (SOD) activity. CONCLUSION: Taken together our observation indicated that subtoxic concentration of aforementioned fractions of A. biennis hydroetanolic extract has protective effect against apoptosis induced by DOX in PC12 cell. The results highlighted that fractions C and D may exert cytoprotective effects through their antioxidant actions. PMID- 27403258 TI - DNA fragmentation and oxidative stress compromise sperm motility and survival in late pregnancy exposure to omega-9 fatty acid in rats. AB - OBJECTIVES: The aim of this study was to evaluate the oxidative status and DNA integrity in testes of wistar rat offspring exposed to omega-9 monounsaturated (MUFA) at different times of late organogenesis. MATERIALS AND METHODS: Sixty female rats were divided into six groups of 10 animals. The first group served as control and received the drug vehicle, olive oil (1 ml/kg/day). The second, third, fourth, fifth and sixth group received 1000 mg/kg of oleic acid on gestation day 15 (D15), 16 (D16), 17 (D17), 18 (D18) and 19 (D19), respectively. Male pups were allowed to attain puberty and thereafter, blood was taken for hormonal analyses. Sperm count and motility were assessed. Testes homogenate was used for the determination of biochemical variables. Testes DNA was also determined. RESULTS: The results showed that sperm count and motility were significantly decreased in the treated groups as compared to the control. There was a marked increase in the malondialdehyde level in rat testes from all of the treated groups as compared to the control (P<0.05). DNA from the testes of rats of D19 had the highest level of fragmentation as compared to the control. CONCLUSION: Omega-9 MUFA exposure in utero imposes negative effects on sperm variables and increases the level of sperm DNA fragmentation and oxidative stress. PMID- 27403259 TI - Difference in transient ischemia-induced neuronal damage and glucose transporter 1 immunoreactivity in the hippocampus between adult and young gerbils. AB - OBJECTIVES: The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1)-immunoreactive microvessels in their ischemic hippocampal CA1 region. MATERIALS AND METHODS: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry. RESULTS: About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion. CONCLUSION: CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults. PMID- 27403260 TI - Evaluation, prediction and optimization the ultrasound-assisted extraction method using response surface methodology: antioxidant and biological properties of Stachys parviflora L. AB - OBJECTIVES: To optimize the extraction method using response surface methodology, extract the phenolic compounds, and identify the antioxidant and biological properties of Stachys parviflora L. extracts. MATERIALS AND METHODS: Maceration and ultrasound-assisted extraction (UAE) (4, 7, 10 min treatment time, 40, 70, 100 % high-intensity and 60, 80, 100 % (v v-1) methanol purity) were applied to obtain the extracts. SEM was conducted to provide the microstructure of the extracted plant. MICs (colorimetric assay), MFCs (colony diameter), total phenolic content, total flavonoid content, radical scavenging capacity and extraction efficiency were determined. HPLC analysis was applied to measure the existent phenolic compounds. RESULTS: A quadratic model (4 min treatment time, 74.5 % high-intensity and 74.2 % solvent purity) was suggested as the best (TPC: 20.89 mg GAE g-1 d.m., TFC: 6.22 mg QEs g-1 d.m., DPPH IC50: 21.86 ug ml-1 and EE: 113.65 mg g-1 d.m.) UAE extraction model. The optimized UAE extract was generally more effective against Gram-positive microorganisms (MIC: 10-20; MBC: 10-40 (mg ml-1)) than Gram-negative ones (MIC: 40; MBC: >40 (mg ml-1)). Moreover, it (MGI: 2.32-100 %) revealed more anti-mold activity than maceration (MGI: <28.77 %). Explosive disruption of the cell walls, therefore, enhanced extraction yield by acoustic cavitation, was elucidated using SEM. Caffeic acid, tannic acid, quercetin, trans ferulic acid and rosmarinic acid were determined as the phenolic compounds in the optimized extract. CONCLUSION: RSM optimization was successfully applied for UAE from S. parviflora. The considerable antioxidant and biological properties were attributed to the phenolic compounds. PMID- 27403261 TI - Administration of orexin receptor 1 antagonist into the rostral ventromedial medulla increased swim stress-induced antinociception in rat. AB - OBJECTIVES: Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA). MATERIALS AND METHODS: Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive responses were measured by formalin test (50 ul injection of formalin 2% subcutaneously into hind paw) and, pain related behaviors were monitored for 90 min following intra-microinjection of SB-334867 (orexin receptor 1 antagonist) into RVM. RESULTS: Exposure to swimming stress test after administration of SB-334867 into RVM significantly reduces the formalin-induced nociceptive behaviors in phase1, interphase, and phase 2 in rats. CONCLUSION: The result demonstrated the involvement of OXR1 in antinociceptive behaviors induced by swim stress in RVM. PMID- 27403262 TI - Design of eudragit RL nanoparticles by nanoemulsion method as carriers for ophthalmic drug delivery of ketotifen fumarate. AB - OBJECTIVES: Ketotifen fumarate (KF) is a selective and noncompetitive histamine antagonist (H1-receptor) that is used topically in the treatment of allergic conditions of rhinitis and conjunctivitis. The aim of this study was to formulate and improve an ophthalmic delivery system of KF. Ocular nanoparticles were prepared with the objective of reducing the frequency of administration and obtaining controlled release to improve the anti-inflammatory drug delivery. MATERIALS AND METHODS: In the present study, ocular KF loaded Eudragit RL 100 nanoparticles were prepared using O/W solvent diffusion method. The nanoparticles were evaluated for particle size, entrapment efficiency, surface morphology, X ray diffraction (XRD), Fourier transform spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro release and permeation studies were also carried out on nanoparticles. RESULTS: An average size range of 182 to 314.30 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Drug release for all formulations after 24 hr was between 65.51% and 88.82% indicating effective controlled release property of KF. The mechanism of drug release for best formulation was found to be fickian diffusion mechanism. KF nanoparticles containing high polymer concentration (1:15) presented a faster drug release and a higher drug penetration; on the contrary, nanoparticles containing low polymer concentration (1:7.5) were able to give a more sustained release of the drug and thus a slower KF permeation through the cornea. CONCLUSION: The study revealed that KF NPs were capable of releasing the drug for a prolonged period of time and increasing the ocular bioavailability. PMID- 27403263 TI - Alpha-tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells. AB - OBJECTIVES: Multiple sclerosis (MS) is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E) is an important component of human diet with antioxidant activity, which protects the body's biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and treated EAE with alpha-tocopherol (AT) which is the main content of Vit E. MATERIALS AND METHODS: Twenty C57BL/6 adult female mice were used and divided into two groups randomly. EAE was induced with myelin oligodendrocyte glycoprotein (MOG), and one group was treated with AT, at a dose of 100 mg/kg on the 3(th) day post-immunization with MOG, the other group was treated with 1% alcohol. Mice were euthanized on day 14, post-immunization, spleens were removed for assessing splenocytes proliferation and cytokine profile, and spinal cords were dissected to assess the infiltration of inflammatory cells in spinal cord. RESULTS: AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-gamma (Th1 cytokine), though the other cytokines were only affected slightly. CONCLUSION: According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS. PMID- 27403264 TI - Enhanced expression of transient receptor potential channel 3 in uterine smooth muscle tissues of lipopolysaccharide-induced preterm delivery mice. AB - OBJECTIVES: We aimed to investigate the influence of transient receptor potential channel 3 (TRPC3) on lipopolysaccharide-induced (LPS) preterm delivery mice. MATERIALS AND METHODS: Mice were randomly assigned to the four groups: an unpregnant group, a mid-pregnancy group (E15), a term delivery group, and an LPS induced preterm delivery group (intraperitoneal injection LPS at 15 days). Uterine smooth muscles were obtained through caesarean section; TRPC3 expression was measured by real-time PCR, western blotting, and immunohistochemistry. A specific inhibitor of TRPC3 (SKF96365) was injected into the LPS-induced preterm delivery group to determine whether the delivery interval was prolonged. RESULTS: TRPC3 was primarily expressed in the uterine smooth muscle layer. In addition, the LPS-induced preterm delivery group had an obviously higher expression level of TRPC3 mRNA and protein compared with the unpregnant and E15 groups, which were close to term delivery. More importantly, SKF96365 prolongs the delivery interval of LPS-induced preterm delivery mice. CONCLUSION: Enhanced expression of TRPC3 may be associated with LPS-induced preterm delivery in mice. The specific inhibitor of TRPC3 (SKF96365) may be helpful for clinical treatment of preterm delivery. PMID- 27403265 TI - Breviscapine prevents downregulation of renal water and sodium transport proteins in response to unilateral ureteral obstruction. AB - OBJECTIVES: Our recent report indicates that breviscapine play a protective role of the kidney by down-regulating transforming growth factor-beta1(TGF-beta1), alpha-smooth muscle actin (alpha-SMA) and alleviating interstitial fibrosis following unilateral ureteral obstruction (UUO). In this study, we investigate the effect of breviscapine on changes of renal water and sodium transport proteins in response to UUO. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 3 groups, sham group, UUO group and UUO treat with breviscapine. After 4, 7 and 14 days, histologic changes and interstitial collagen were determined microscopically following hematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Aquaporins (AQP-2) and gamma-epithelial sodium channel (gamma-ENaC) were investigated using immunohistochemistry and Western blot in each group. RESULTS: Breviscapine treatment decrease the tubular injury index and the degree of interstitial collagen deposition significantly compared with the UUO group (P<0.05). Breviscapine treatment also significantly reduced downregulation of AQP2 and gamma-ENaC compared to those subjected to the same time course of obstruction in UUO group (P<0.05). CONCLUSION: These results demonstrate that breviscapine could prevent downregulation of renal water and sodium transport proteins in response to UUO so as to protect obstructed kidney. PMID- 27403266 TI - Molecular Typing of Mycobacterium Tuberculosis Strains: A Fundamental Tool for Tuberculosis Control and Elimination. AB - Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. An improvement of the strategies for disease control is necessary in both low- and high-incidence TB countries. Clinicians, epidemiologists, laboratory specialists, and public health players should work together in order to achieve a significant reduction in TB transmission and spread of drug resistant strains. Effective TB surveillance relies on early diagnosis of new cases, appropriate therapy, and accurate detection of outbreaks in the community, in order to implement proper TB control strategies. To achieve this goal, information from classical and molecular epidemiology, together with patient clinical data need to be combined. In this review, we summarize the methodologies currently used in molecular epidemiology, namely molecular typing. We will discuss their efficiency to phylogenetically characterize Mycobacterium tuberculosis isolates, and their ability to provide information that can be useful for disease control. We will also introduce next generation sequencing as the methodology that potentially could provide in a short time both, detection of new outbreaks and identification of resistance patterns. This could envision a potential of next generation sequencing as an important tool for accurate patient management and disease control. PMID- 27403268 TI - New Antituberculosis Drugs: From Clinical Trial to Programmatic Use. AB - Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of in-patient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance. PMID- 27403269 TI - Tuberculosis 2015: Burden, Challenges and Strategy for Control and Elimination. AB - Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide, accounting for about 9.6 million new cases and 1.5 million deaths annually. The poorest and socially excluded groups carry the largest burden of disease, which makes it essential to properly address the social determinants of health through poverty reduction measures and targeted interventions on high-risk populations. The spread of multidrug-resistance TB requires special attention and highlights the need to foster research on TB diagnostics, new drugs and vaccines. Although many advances have been made in the fight against TB over the last twenty years, a lot is still needed to achieve global elimination. The new end-TB strategy that was first launched in 2014 by the World Health Organization, is fully in line with the seventeen Sustainable Development Goals that came into effect since January 2016 and sets ambitious goals for the post-2015 agenda. A 90% reduction in TB-related mortality and an 80% decline in TB incidence within 2030 as well as the abolition of catastrophic expenditures for TB-affected people are the main targets of this strategy. Strong government commitment and adequate financing from all countries together with community engagement and appropriate investments in research are necessary in order to reach these objectives. PMID- 27403267 TI - Tuberculosis Biomarkers: From Diagnosis to Protection. AB - New approaches to control tuberculosis (TB) worldwide are needed. In particular, new tools for diagnosis and new biomarkers are required to evaluate both pathogen and host key elements of the response to infection. Non-sputum based diagnostic tests, biomarkers predictive of adequate responsiveness to treatment, and biomarkers of risk of developing active TB disease are major goals. Here, we review the current state of the field. Although reports on new candidate biomarkers are numerous, validation and independent confirmation are rare. Efforts are needed to reduce the gap between the exploratory up-stream identification of candidate biomarkers, and the validation of biomarkers against clear clinical endpoints in different populations. This will need a major commitment from both scientists and funding bodies. PMID- 27403271 TI - A New Era in the Control of Tuberculosis. PMID- 27403270 TI - Active Tuberculosis Case Finding Interventions Among Immigrants, Refugees and Asylum Seekers in Italy. AB - In Italy tuberculosis (TB) is largely concentrated in vulnerable groups such as migrants and in urban settings. We analyzed three TB case finding interventions conducted at primary centers and mobile clinics for regular/irregular immigrants and refugees/asylum seekers performed over a four-year period (November 2009 March 2014) at five different sites in Rome and one site in Milan, Italy. TB history and presence of symptoms suggestive of active TB were investigated by verbal screening through a structured questionnaire in migrants presenting for any medical condition to out-patient and mobile clinics. Individuals reporting TB history or symptoms were referred to a TB clinic for diagnostic workup. Among 6347 migrants enrolled, 891 (14.0%) reported TB history or symptoms suggestive of active TB and 546 (61.3%) were referred to the TB clinic. Of them, 254 (46.5%) did not present for diagnostic evaluation. TB was diagnosed in 11 individuals representing 0.17% of those screened and 3.76% of those evaluated. The overall yield of this intervention was in the range reported for other TB screening programs for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. PMID- 27403272 TI - Psychological Distress and Emotional Pain Among Adult Attendees of a Dental Clinic: A Case-Control Study. AB - We set out to carry out a case-control evaluation of psychological distress and emotional pain among adult attendees of a Nigerian dental clinic. A total of 201 subjects, made up of 101 dental patients (test group) matched with age and sex with 100 normal subjects (controls), was recruited into the study. All participants completed a designed socio-demographic questionnaire. General Health Question naire and Psyche ache Assessment Schedule were also administered to assess psychological distress based on cut-off scores >=3 and emotional pain based on cut-off scores >=28 respectively. The mean ages of study and control group were 33 (+/-12) and 36 (+/-13) years respectively, and both study and control groups were not significantly different in all the assessed socio demographic parameters. Overall, 21.8% (n=22) of the subjects had psychological distress, while only 7% of the control group had psychological distress. This difference was statistically significant (P=0.003). Similarly, there was significant difference in the experience of psyche ache (unbearable psychological pain) as over a third of the dental patients (37.6%, n=38) had emotional pain, while only 13% of the controls experienced psych ache (P<0.001). In this study, the burden of psychological distress and emotional pain was many-fold in dental patients when compared with the controls. PMID- 27403273 TI - Detection of Mental Disorders Other Than Depression with the Edinburgh Postnatal Depression Scale in a Sample of Pregnant Women in Northern Mexico. AB - We sought to evaluate the capacity of the Edinburgh Postnatal Depression Scale (EPDS) in discriminating mental disorders other than depression in pregnant women in northern Mexico. Three hundred pregnant women attending prenatal consultations in a public hospital in Durango City, Mexico submitted a validated EPDS and were examined for mental disorders other than depression using the Diagnostic and Statistical Manual of Mental Disorders - 4(th) Ed. (DSM-IV) criteria. Sensitivity and specificity of cut-off points of the EPDS, and positive and negative predictive values were calculated. Of the 300 pregnant women studied, 21 had mental disorders other than depression by the DSM-IV criteria. The best EPDS score for screening mental disorders other than depression was 8/9. This threshold showed a sensitivity of 52.4%, a specificity of 67.0%, a positive predictive value of 11.5%, a negative predictive value of 95.4%, and an area under the curve of 0.643 (95% confidence interval: 0.52-0.76). The EPDS can be considered for screening mental disorders other than depression in Mexican pregnant women whenever a cut-off score of 8/9 is used. However, the tool showed small power to separate pregnant women with and without mental disorders other than depression. PMID- 27403274 TI - The Quality of Life in Girls with Rett Syndrome. AB - Nowadays, quality of life is receiving an increasing attention in all scientific areas. Rett syndrome (RTT) is a rare neurological development, affecting mainly females. The congenital disease affects the central nervous system, and is one of the most common causes of severe intellectual disability. The aim of our study is to evaluate the effect of RTT on the quality of life of people who are affected. Both parents of 18 subjects, all female, diagnosed with RTT, took part in the research. Quality of life was assessed using the Italian version of the Impact of Childhood Illness Scale. This scale consists of 30 questions that investigate the effect of illness on children, parents and families. For each question, the parent was asked to rate two variables: frequency and importance. Another questionnaire was administered to obtain medical history, diagnostic and therapeutic data of the persons with RTT. Our data show that RTT has a considerable impact on both the child's development and the entire family. Parents' answers demonstrated that their child's illness had consequences for the child and how the family coped with it. For this reason, attention should be directed at psychological and social aspects, as well as attitudes, manners, reactions and effects such disturbances can have on the entire family. PMID- 27403275 TI - The Effects of Symptoms, Diagnostic Labels, and Education in Psychiatry on the Stigmatization Towards Schizophrenia: A Questionnaire Survey Among a Lay Population in Japan. AB - This questionnaire survey was conducted to study the determinants of stigmatization toward schizophrenia in Japan. A total of 1003 persons living in Kumamoto Prefecture (mean age 25.5; SD=14.1) participated in this study through convenience sampling. They read one of four case vignettes about a person with mental illness and answered questions about their attitudes toward the case. Vignettes varied in terms of descriptions of symptoms (schizophrenia vs. depression) and presentation of the diagnostic label of schizophrenia (yes or no). A path analysis was performed to examine the effects of symptoms, diagnostic label, experience of education in psychiatry, and demographic features on stigmatizing attitudes. Results showed that schizophrenic symptoms, diagnostic label of schizophrenia, and experience of education in psychiatry were significantly associated with stigmatization toward the case. Interaction terms of these variables did not show significant association with stigmatization. These results highlight the importance of optimizing education techniques about mental illness so as to avoid cultivating stigmatizing attitudes toward schizophrenia. PMID- 27403276 TI - Risks and Benefits of Rapid Clozapine Titration. AB - Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia. PMID- 27403277 TI - Tennis Enhances Well-being in University Students. AB - Sports and physical activity are widely recommended, both as guidelines and in clinical practice, because of their broad range of positive effects on health, depression, anxiety, and psychological well-being. While several studies have examined the anti-depressive and anxiolytic effects of physical activity in clinical populations, and fewer studies have focused on the nonclinical populations, the relationship between tennis and well-being has not been clearly investigated. This study was carried out with 76 student volunteers from Kocaeli University (Turkey) who had chosen tennis lessons as their University. The tennis exercise program consisted of 90-minute basic tennis skills lessons for 13 weeks. At the beginning and at the end of the study, the students were given the Symptom Checklist-90-Revised (SCL-90-R), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) scales, and were evaluated by the DeWitt-Dugan Tennis Service Test, the DeWitt-Dugan Speed Test, and the Dyer Backboard Tennis Test. Upon evaluating the students' pre- and post-test scores, we concluded that their BDI and BAI scores had significantly decreased, with the most significant decreases seen in several sub-scores of the SCL-90-R; their tennis skills, meanwhile, increased significantly. This study shows that partaking in tennis exercise once a week decreases depression and anxiety symptoms and enhances well being in healthy young people. PMID- 27403278 TI - Psychiatric Disorders Associated with 22q11.2 Deletion Syndrome. PMID- 27403279 TI - A Link Between Maternal Thyroid Hormone and Sexual Orientation? PMID- 27403280 TI - Patterns of care for patients with advanced soft tissue sarcoma: experience from Australian sarcoma services. AB - BACKGROUND: There is a paucity of data on the current management of patients with advanced soft tissue sarcoma (STS) in the Australian health care setting. This study utilised the Australian sarcoma database to evaluate the patterns of care delivered to patients with advanced STS at Australian sarcoma services. METHODS: Prospectively collected data from six sarcoma centres in Australia were sourced to identify patients diagnosed with advanced STS between 1 January 2010 and 31 December 2012. Descriptive statistics were analysed for patient demographics, clinicopathological characteristics and treatment patterns. Overall survival was estimated using the Kaplan-Meier product limit method. RESULTS: Of 253 patients with advanced STS, four major STS subtypes were identified: undifferentiated pleomorphic sarcoma (23 %), leiomyosarcoma (17 %), liposarcoma (14 %), and synovial sarcoma (8 %); with the rest grouped as "other STS" (38 %). Approximately one-third of patients received palliative systemic therapy with the most common first-line therapy being doxorubicin alone (50 %). A small percentage of patients participated in clinical trials (20 %). Palliative radiotherapy was utilised mostly for treatment of symptomatic distant metastases and one-third of patients underwent metastasectomy, most commonly for pulmonary metastases. The median overall survival (OS) in this series was 18 months and no significant difference in OS was observed across different STS histological subtypes. CONCLUSIONS: This is the first detailed study outlining patterns of care for Australian patients with advanced STS managed at sarcoma services. These data highlight a particular area of weakness in the lack of clinical trials for sarcoma patients and also serve as an important reference point for understanding how practice may change over time as treatment options evolve. PMID- 27403281 TI - Perception of peer physical examination in two Australian osteopathy programs. AB - BACKGROUND: Peer physical examination (PPE) is an efficient and practical educational approach whereby students can practise their examination skills on each other before commencing clinical practice with actual patients. Little is known about the use of PPE in osteopathy education. METHODS: Students in Year 1 of the osteopathy programs at Victoria University (Melbourne, Australia) and Southern Cross University (Lismore, Australia) completed the Examining Fellow Students and the Peer Physical Examination questionnaires prior to, and at the completion of, their first 12-week teaching session. Descriptive statistics were generated for each questionnaire. The McNemar and sign tests were used to evaluate differences between each questionnaire administration. Logistic regression was used to evaluate the influence of demographics on responses to both questionnaires. RESULTS: Results showed that students in both programs were generally willing to examine non-sensitive areas both before and after the 12 week teaching session. Students' were less apprehensive about PPE at the end of the teaching session, and this was reinforced by results for previous exposure to PPE in other courses. Consistent with previous studies, unwillingness to participate in PPE was associated with being female, being born outside Australia, holding religious beliefs, and being older. CONCLUSIONS: This is the first study to explore students' perceptions of PPE in this cohort and provides a basis for further work, including evaluating longer term changes in student perception of PPE, and whether these perceptions extend to practising manual therapy techniques. This study demonstrates that perceptions about PPE reported in medicine and other disciplines, namely that unwillingness to participate in PPE is associated with being female, being born outside Australia, holding religious beliefs, and being older, also apply to osteopathy. These findings are significant for all manual therapy students who spend a substantial portion of their course developing skills in PPE and practising manual therapy techniques. They highlight the need for curriculum development that acknowledges the importance of good practice in PPE, including discussions about body image, feedback skills training for educators, and providing detailed information to students about what to expect in practical skills classes before they commence their course. PMID- 27403282 TI - Erratum to: Spinal manipulative therapy, Graston technique(r) and placebo for non specific thoracic spine pain: a randomised controlled trial. AB - [This corrects the article DOI: 10.1186/s12998-016-0096-9.]. PMID- 25352983 TI - Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis. AB - Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages. PMID- 27239278 TI - Combined analysis of trabectome and phaco-trabectome outcomes by glaucoma severity. AB - Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. In the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+/-0.56 and 3.86+/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities. PMID- 27303634 TI - Infrastructure for genomic interactions: Bioconductor classes for Hi-C, ChIA-PET and related experiments. AB - The study of genomic interactions has been greatly facilitated by techniques such as chromatin conformation capture with high-throughput sequencing (Hi-C). These genome-wide experiments generate large amounts of data that require careful analysis to obtain useful biological conclusions. However, development of the appropriate software tools is hindered by the lack of basic infrastructure to represent and manipulate genomic interaction data. Here, we present the InteractionSet package that provides classes to represent genomic interactions and store their associated experimental data, along with the methods required for low-level manipulation and processing of those classes. The InteractionSet package exploits existing infrastructure in the open-source Bioconductor project, while in turn being used by Bioconductor packages designed for higher-level analyses. For new packages, use of the functionality in InteractionSet will simplify development, allow access to more features and improve interoperability between packages. PMID- 27403286 TI - Consensus Document on Supraventricular Arrhythmias: A Valuable Initiative from EHRA. PMID- 27403287 TI - Controversy Surrounding ROCKET-AF: A Call for Transparency, But Should We Be Changing Practice? PMID- 27403288 TI - Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis. AB - A wide range of ion channels, transporters, signaling pathways and tissue structure at a microscopic and macroscopic scale regulate the electrophysiological activity of the heart. Each region of the heart has optimised these properties based on its specific role during the cardiac cycle, leading to well-established differences in electrophysiology, Ca(2+) handling and tissue structure between atria and ventricles and between different layers of the ventricular wall. Similarly, the right ventricle (RV) and left ventricle (LV) have different embryological, structural, metabolic and electrophysiological features, but whether interventricular differences promote differential remodeling leading to arrhythmias is not well understood. In this article, we will summarise the available data on intrinsic differences between LV and RV electrophysiology and indicate how these differences affect cardiac function. Furthermore, we will discuss the differential remodeling of both chambers in pathological conditions and its potential impact on arrhythmogenesis. PMID- 27403290 TI - Post-extrasystolic Blood Pressure Potentiation as a Risk Predictor in Cardiac Patients. AB - For more than 100 years physicians have observed that heartbeats following extrasystolic beats are characterised by augmented myocardial contractility. This phenomenon was termed post-extrasystolic potentiation (PESP). In the 1970s it was first noted that PESP measured at the blood pressure level is typically pronounced in heart failure patients. Only recently, it was shown that PESP measured non-invasively as post-extrasystolic blood pressure potentiation was a strong and independent predictor of death in survivors of myocardial infarction and in patients with chronic heart failure. A similar parameter (PESPAfib) can be also assessed in patients with atrial fibrillation. PESP and PESPAfib can be understood as non-invasive parameters that indicate myocardial dysfunction. They have the potential to improve risk stratification strategies for cardiac patients. PMID- 27403289 TI - Post-extrasystolic Potentiation: Link between Ca(2+) Homeostasis and Heart Failure? AB - Post-extrasystolic potentiation (PESP) describes the phenomenon of increased contractility of the beat following an extrasystole and has been attributed to changes in Ca(2+) homeostasis. While this effect has long been regarded to be a normal physiological phenomenon, a number of reports describe an enhanced potentiation of the post-extrasystolic beat in heart failure patients. The exact mechanism of this increased PESP is unknown, but disruption of normal Ca(2+) handling in heart failure may be the underlying cause. The use of PESP as a prognostic marker or therapeutic intervention have recently regained new attention, however, the value of the application of PESP in the clinic is still under debate. In this review, the mechanism of PESP with regard to Ca(2+) in the normal and failing heart will be discussed and the possible diagnostic and therapeutic role of this phenomenon will be explored. PMID- 27403291 TI - Periodic Repolarisation Dynamics: A Natural Probe of the Ventricular Response to Sympathetic Activation. AB - Periodic repolarisation dynamics (PRD) refers to low-frequency (<=0.1Hz) modulations of cardiac repolarisation instability. Spontaneous PRD can be assessed non-invasively from 3D high-resolution resting ECGs. Physiological and experimental studies have indicated that PRD correlates with efferent sympathetic nerve activity, which clusters in low-frequency bursts. PRD is increased by physiological provocations that lead to an enhancement of sympathetic activity, whereas it is suppressed by pharmacological beta-blockade. Electrophysiological studies revealed that PRD occurs independently from heart rate variability. Increased PRD under resting conditions is a strong predictor of mortality in post myocardial infarction (post-MI) patients, yielding independent prognostic value from left-ventricular ejection fraction (LVEF), heart rate variability, the Global Registry of Acute Coronary Events score and other established risk markers. The predictive value of PRD is particularly strong in post-MI patients with preserved LVEF (>35 %) in whom it identifies a new high-risk group of patients. The upcoming Implantable Cardiac Monitors in High-Risk Post-Infarction Patients with Cardiac Autonomic Dysfunction and Moderately Reduced Left Ventricular Ejection Fraction (SMART-MI) trial will test prophylactic strategies in high-risk post-MI patients with LVEF 36-50 % identified by PRD and deceleration capacity of heart rate (NCT02594488). PMID- 27403292 TI - Microvolt T-wave Alternans: Where Are We Now? AB - Microvolt T-wave alternans (TWA), characterised as beat-to-beat fluctuation of T wave amplitude and morphology, is an electrophysiological phenomenon associated clinically with impending ventricular arrhythmias and is an important marker of arrhythmia risk. Currently, two main methods for the detection of TWA exist, namely, the spectral method and the time-domain modified moving average method; both are discussed in this review. Microvolt TWA has been associated with cardiovascular mortality and sudden cardiac death in several clinical studies involving >14,000 subjects with reduced as well as preserved left ventricular function. Although TWA appears to be a useful marker of susceptibility for lethal ventricular arrhythmias and cardiovascular death, so far there is no sufficient evidence from randomised clinical trials to support its use in guiding therapy. However, several ongoing trials are expected to provide more information about the clinical use of TWA testing. PMID- 27403293 TI - The Role of Flecainide in the Management of Catecholaminergic Polymorphic Ventricular Tachycardia. AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder, with symptoms including syncope and sudden cardiac death due to polymorphic VT or ventricular fibrillation typically triggered by exercise or emotions in the absence of structural heart disease. The cornerstone of medical therapy for CPVT is beta-blockers. However, recently flecainide has been added to the therapeutic arsenal for CPVT. In this review we summarise current data on the efficacy and role of flecainide in the treatment of CPVT. PMID- 27403294 TI - Novel Interventional Strategies for the Treatment of Atrial Fibrillation. AB - The landscape of the invasive management of atrial fibrillation, the most common sustained arrhythmia in humans, has changed dramatically in the last decade owing to numerous advances in arrhythmia mapping and ablation technologies. The current review critically appraises novel interventional strategies for the treatment of atrial fibrillation with a focus on clinical effectiveness and safety. PMID- 27403295 TI - Pacing and Defibrillators in Complex Congenital Heart Disease. AB - Device therapy in the complex congenital heart disease (CHD) population is a challenging field. There is a myriad of devices available, but none designed specifically for the CHD patient group, and a scarcity of prospective studies to guide best practice. Baseline cardiac anatomy, prior surgical and interventional procedures, existing tachyarrhythmias and the requirement for future intervention all play a substantial role in decision making. For both pacing systems and implantable cardioverter defibrillators, numerous factors impact on the merits of system location (endovascular versus non-endovascular), lead positioning, device selection and device programming. For those with Fontan circulation and following the atrial switch procedure there are also very specific considerations regarding access and potential complications. This review discusses the published guidelines, device indications and the best available evidence for guidance of device implantation in the complex CHD population. PMID- 27403296 TI - Cardiac Implantable Electronic Device Infection in Patients at Risk. AB - The incidence of infection following implantation of cardiac implantable electronic devices (CIEDs) is increasing at a faster rate than that of device implantation. Patients with a CIED infection usually require hospitalisation and complete device and lead removal. A significant proportion die from their infection. Transvenous lead extraction (TLE) is associated with rare but serious complications including major vascular injury or cardiac perforation. Operator experience and advances in lead extraction methods, including laser technology and rotational sheaths, have resulted in procedures having a low risk of complication and mortality. Strategies for preventing CIED infections include intravenous antibiotics and aseptic surgical techniques. An additional method to reduce CIED infection may be the use of antibacterial TYRXTM envelope. Data from non-randomised cohort studies have indicated that antibacterial envelope use can reduce the incidence of CIED infection by more than 80 % in high-risk patients and a randomised clinical trial is ongoing. PMID- 27403298 TI - Creating an effective clinical registry for rare diseases. AB - The exposure of clinicians to patients with rare gastrointestinal diseases is limited. This hurts clinical studies, which impedes accumulation of scientific knowledge on the natural disease course, treatment outcomes and prognosis in these patients. An excellent method to detect patterns on an aggregate level that would not be possible to discover in individual cases, is a registry study. This paper aims to describe a template to create a successful international registry for rare diseases. We focus mainly on rare hepatic diseases, but lessons from this paper serve other fields in medicine, as well. PMID- 27403297 TI - The role for protein tyrosine phosphatase non-receptor type 22 in regulating intestinal homeostasis. AB - Inflammatory bowel disease represents a chronic intestinal inflammation. Recent knowledge suggests a crucial role for genetic, immunological and bacterial factors in inflammatory bowel disease pathogenesis. Variations within the gene locus encoding PTPN22 have been associated with inflammatory bowel disease. PTPN22 is critically involved in controlling immune cell activation and thereby plays an important role in maintaining intestinal homeostasis. Although in B and T cells the mechanism showing how PTPN22 affects cell signalling pathways is well studied, its role in myeloid cells remains less defined. Regulation of the innate immune system plays an essential role in the intestine, and levels of PTPN22 in myeloid cells are drastically reduced in the intestine of inflammatory bowel disease patients. Therefore, additional studies to define the role of PTPN22 in myeloid cells might clearly enhance our understanding of how PTPN22 contributes to intestinal homeostasis. PMID- 27403299 TI - Real-time diagnosis of H. pylori infection during endoscopy: Accuracy of an innovative tool (EndoFaster). AB - BACKGROUND: EndoFaster is novel device able to perform real-time ammonium measurement in gastric juice allowing H. pylori diagnosis during endoscopy. This large study aimed to validate the accuracy of EndoFaster for real-time H. pylori detection. METHODS: Consecutive patients who underwent upper endoscopy in two centres were prospectively enrolled. During endoscopy, 4 ml of gastric juice were aspirated to perform automatic analysis by EndoFaster within 90 seconds, and H. pylori was considered present (>62 ppm/ml) or absent (<=62 ppm/ml). Accuracy was measured by using histology as gold standard, and (13)C-urea breath test (UBT) in discordant cases. Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were calculated. RESULTS: Overall, 189 patients were enrolled, but in seven (3.4%) the aspirated gastric juice amount was insufficient to perform the test. The accuracy, sensitivity, specificity, PPV, and NPV were 87.4%, 90.3%, 85.5%, 80.2%, 93.1%, respectively, and 92.6%, 97.1%, 89.7%, 85.9%, 98.0%, respectively, when H. pylori status was reclassified according to the UBT result in discordant cases. CONCLUSIONS: This study found a high accuracy/feasibility of EndoFaster for real-time H. pylori diagnosis. Use of EndoFaster may allow selecting those patients in whom routine gastric biopsies could be avoided. PMID- 27403300 TI - Low risk of adenocarcinoma and high-grade dysplasia in patients with non dysplastic Barrett's esophagus: Results from a cohort from a country with low esophageal adenocarcinoma incidence. AB - BACKGROUND: The risk of esophageal adenocarcinoma (EAC) in non-dysplastic Barrett's esophagus (NDBE) is considered to be approximately 0.3% per year or even lower, according to population-based studies. Data from countries with low EAC incidence are scarce. Our principal aim was to determine the incidence of high-grade dysplasia (HGD) and EAC in NDBE. Our secondary aims were to identify the predictors of progression and to calculate the incidence of HGD/EAC, by using the calculation method for surveillance time in population-based studies. MATERIALS AND METHODS: A cohort of NDBE patients was prospectively followed up. Cases of HGD and EAC (study end points) diagnosed during the first year of follow up were considered as prevalent. Only cases with an endoscopic surveillance time > 1 year were included in our analysis. RESULTS: We enrolled 331 patients (251 men) in the surveillance program. Their median age was 59 years (interquartile range (IQR): 47-67 years). Their median NDBE length was 3 cm (IQR: 2-4 cm). Of these patients, 80 died during the follow-up (one from EAC) and two were lost to follow-up. After 2284 patient-years of endoscopic follow-up (median surveillance time, 5 years (IQR: 2-10 years)), we found that five cases of HGD and two cases of EAC were diagnosed. The incidence of HGD/EAC was 3.1 cases per 1000 patient years (95% CI: 1.3-6.0) and that of EAC was 0.9 (95% CI: 0.2-2.9). The incidence of HGD/EAC in short segments (<= 3 cm) was 0.7 cases per 1000 patient-years (95% CI: 0.3-3.4). The sole variable that we found associated with progression was NDBE length. If the total surveillance time was considered (3537 patient-years), the incidence of HGD and EAC was only slight lower. CONCLUSIONS: The incidence of HGD and EAC was very low in NDBE. Therefore, current surveillance guidelines must be reassessed, at least for short-segment BE. PMID- 27403301 TI - Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and/or discomfort. Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear. OBJECTIVE: This study was designed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms. METHODS: A randomized, double blind, placebo-controlled trial has been performed in 379 subjects with diagnosed IBS. Subjects were randomly supplemented with the probiotics (1000 mg) or placebo for 12 weeks. Questionnaires (gastrointestinal symptoms, stools, wellbeing, and quality of life) were completed. Primary endpoint was percentage of responders defined as having a 50% decrease in the weekly average "intestinal pain/discomfort score" for at least 4 out of the last 8 weeks of the study. RESULTS: There was no overall benefit of S. cerevisiae I 3856 on IBS symptoms and wellbeing in the study population. Moreover, S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects (p > 0.05). Planned subgroup analyses showed significant effect in the IBS-C subjects: improvement of gastrointestinal symptoms was significantly higher in active group, compared to placebo, on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation. CONCLUSIONS: In this study, S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients. However, it seems to have an effect in the subgroup with constipation which needs further studies to confirm (NCT01613456 in ClinicalTrials.gov registry). PMID- 27403302 TI - Determinants of esophageal varices bleeding in patients with advanced hepatocellular carcinoma treated with sorafenib. AB - BACKGROUND AND AIMS: Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), yet treatment safety may be challenged by portal hypertension. We therefore assessed the prevalence, risk factors and clinical consequences of esophageal varices (EVs) in sorafenib-treated patients with HCC. METHODS: Starting in 2008, all compensated patients with advanced or intermediate HCC not eligible for other therapies were consecutively enrolled in a prospective evaluation of sorafenib therapy, all with pretreatment by upper-gastrointestinal endoscopy (UGE). RESULTS: A total of 150 patients received sorafenib for 4.6 (95% CI, 3.3-5.6) months. At baseline, 61 (41%) patients were EV free (group A), 78 (52%) had EVs (61 small EVs (group B), 17 medium/large EVs (group C)) and 11 (7%) previously endoscopically treated EVs (group D). Propranolol was given to all patients with medium/large EVs and those with previous bleeding. Twelve patients (8%) bled from EVs after 36 (18-260) days of sorafenib. During sorafenib, bleeding occurred in six of 26 group B patients with neoplastic portal vein thrombosis (nPVT), three of nine group C patients with nPVT, two of five group D patients with nPVT and one of six without nPVT (p < 0.0001), nPVT being the strongest independent predictor of bleeding by multivariate analysis (HR = 15.4, 95% CI 1.84-129.6). CONCLUSION: UGE screening is worthwhile in HCC patients allocated to sorafenib since it identifies patients with EVs at risk of bleeding during therapy, particularly those with nPVT. PMID- 27403303 TI - Comparison of AIMS65, Glasgow-Blatchford score, and Rockall score in a European series of patients with upper gastrointestinal bleeding: performance when predicting in-hospital and delayed mortality. AB - OBJECTIVE: AIMS65 is a score designed to predict in-hospital mortality, length of stay, and costs of gastrointestinal bleeding. Our aims were to revalidate AIMS65 as predictor of inpatient mortality and to compare AIMS65's performance with that of Glasgow-Blatchford (GBS) and Rockall scores (RS) with regard to mortality, and the secondary outcomes of a composite endpoint of severity, transfusion requirements, rebleeding, delayed (6-month) mortality, and length of stay. METHODS: The study included 309 patients. Clinical and biochemical data, transfusion requirements, endoscopic, surgical, or radiological treatments, and outcomes for 6 months after admission were collected. Clinical outcomes were in hospital mortality, delayed mortality, rebleeding, composite endpoint, blood transfusions, and length of stay. RESULTS: In receiver-operating characteristic curve analyses, AIMS65, GBS, and RS were similar when predicting inpatient mortality (0.76 vs. 0.78 vs. 0.78). Regarding endoscopic intervention, AIMS65 and GBS were identical (0.62 vs. 0.62). AIMS65 was useless when predicting rebleeding compared to GBS or RS (0.56 vs. 0.70 vs. 0.71). GBS was better at predicting the need for transfusions. No patient with AIMS65 = 0, GBS <= 6, or RS <= 4 died. Considering the composite endpoint, an AIMS65 of 0 did not exclude high risk patients, but a GBS <= 1 or RS <= 2 did. The three scores were similar in predicting prolonged in-hospital stay. Delayed mortality was better predicted by AIMS65. CONCLUSION: AIMS65 is comparable to GBS and RS in essential endpoints such as inpatient mortality, the need for endoscopic intervention and length of stay. GBS is a better score predicting rebleeding and the need for transfusion, but AIMS65 shows a better performance predicting delayed mortality. PMID- 27403304 TI - Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study. AB - BACKGROUND AND AIM: This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy. METHODS: Patients who failed first- and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of <80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy. RESULTS: Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation positive strains (n = 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively. CONCLUSION: Both the 10 day and 14-day therapies were effective as rescue regimens. In particular, the 14 day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy. PMID- 27403305 TI - Co-infection with Helicobacter pylori and Epstein-Barr virus in benign upper digestive diseases: An endoscopic and serologic pilot study. AB - BACKGROUND: Some gastric cancers are Epstein-Barr virus associated. AIM: To assess the prevalence of Helicobacter pylori and viral co-infection in benign upper digestive diseases. METHODS: One hundred and four outpatients were included in a prospective endoscopic-serologic study. Epstein-Barr virus immunoglobulin G (IgG), immunoglobulin M and viral capsid antigen titres were assayed with an ELISA test. Helicobacter pylori was determined by the modified Giemsa stain and by IgG-chemiluminescence. RESULTS: The overall prevalence of Helicobacter pylori was 56.7%. Duodenal ulcer patients were infected in 72.5 % of the cases, with the prevalence being 33.3% in functional dyspepsia (p = 0.0008) and 25.8% in reflux patients (p = 0.0001). Epstein-Barr virus IgG was detected in 70.1% of the whole group, 75% of duodenal ulcer patients, 51.2% of functional dyspepsia patients (p = 0.04) and 51.6% of the reflux disease cases (p = 0.04). Co-infection with both agents was detected in 60% of duodenal ulcer patients, 18.1% of functional dyspepsia (p = 0.00014) and 12.9% of reflux disease patients (p = 0.00012). Anti viral IgG titre displayed a 31.7 +/- 3.0 cut-off index in duodenal ulcer, 20.5 +/ 3.5 in functional dyspepsia (p = 0.01) and 21.4 +/- 3.6 in reflux cases (p = 0.03). CONCLUSIONS: Both Helicobacter pylori and Epstein-Barr virus, and co infection with these agents, were significantly more prevalent in duodenal ulcer patients than in dyspeptic/reflux patients. PMID- 27403306 TI - Gastric malt lymphoma: Analysis of a series of consecutive patients over 20 years. AB - INTRODUCTION AND AIMS: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori (HP) infection. Our aim was to evaluate demographic, clinical and endoscopic characteristics of gastric MALT lymphoma patients, as well as to analyse response to treatment and factors that affect complete remission (CR) and relapse. We also assessed the long-term prognosis. METHODS: The study involved a retrospective evaluation of consecutive patients admitted with gastric MALT lymphoma (1993-2013). RESULTS: A total of 144 patients (76 men; mean age 56) were included. At stage EI, 94/103 patients (92%) received HP eradication and 78 (83%) achieved CR after a mean period of 7 months (2-63 months) and 67 (86%) remained in CR after a mean follow-up time of 105 months. HP infection status (p = 0.004) and lymphoma localisation to the antrum plus body (p = 0.016) were associated with higher and lower CR rates, respectively. Relapse occurred in 11/78 (14%) patients after a mean period of 21 months. The absence of HP re-infection (p = 0.038), the need of only one eradication regimen (p = 0.009) and antrum lymphomas (p = 0.031) correlated with lower relapse rates. At stage EII, HP eradication was performed in 17/24 patients but only five experienced CR (30%). Among 16 patients diagnosed at stage EIV, nine achieved CR after chemotherapy +/- surgery and 3/7 without remission died due to disease progression. The 5- and 10-year overall disease free survival rates were 90.5% and 79.1%, respectively. CONCLUSIONS: Most patients were diagnosed at an early stage. Eradication therapy was highly effective in inducing complete remission. Long-term evaluation showed that the long-term prognosis was very favourable. PMID- 27403307 TI - Temporary placement of fully covered self-expandable metal stents for the treatment of benign biliary strictures. AB - BACKGROUND: Endoscopic treatment of benign biliary strictures (BBS) can be challenging. OBJECTIVE: To evaluate the efficacy of fully covered self-expandable metal stents (FCSEMS) in BBS. METHODS: Ninety-two consecutive patients with BBS (chronic pancreatitis (n = 42), anastomotic after liver transplantation (n = 36), and post biliary surgical procedure (n = 14)) were included. FCSEMS were placed across strictures for 6 months before endoscopic extraction. Early success rate was defined as the absence of biliary stricture or as a minimal residual anomaly on post-stent removal endoscopic retrograde cholangiopancreatography (ERCP). Secondary outcomes were the final success and stricture recurrence rates as well as procedure-related morbidity. RESULTS: Stenting was successful in all patients. Stenting associated complications were minor and occurred in 22 (23.9%) patients. Migration occurred in 23 (25%) patients. Stent extraction was successful in all but two patients with proximal stent migration. ERCP after the 6 months stenting showed an early success in 84.9% patients (chronic pancreatitis patients: 94.7%, liver transplant: 87.9%, post-surgical: 61.5%) (p = 0.01). Final success was observed in 57/73 (78.1%) patients with a median follow-up of 12 +/- 3.56 months. Recurrence of biliary stricture occurred in 16/73 (21.9%) patients. CONCLUSIONS: FCSEMS placement is efficient for patients with BBS, in particular for chronic pancreatitis patients. Stent extraction after 6 months indwelling, although generally feasible, may fail in a few cases. PMID- 27403308 TI - Symptom burden and consulting behavior in patients with overlapping functional disorders in the US population. AB - BACKGROUND: Regulatory and treatment guidelines focus on individual conditions, yet clinicians often see patients with overlapping conditions. OBJECTIVE: This cross-sectional survey study assesses the impact of overlapping functional dyspepsia (FD), gastroesophageal reflux disease (GERD), irritable bowel syndrome with constipation (IBS-C), and chronic idiopathic constipation (CIC) on symptom burden and consulting behavior. METHODS: Survey participants met Rome III criteria for FD, IBS-C, and/or CIC, and/or reported GERD; participants answered questions about symptom frequency and bothersomeness, work and productivity, and consulting behavior. RESULTS: Of 2641 respondents, 1592 (60.3%) had one condition; 832 (31.5%) had two; and 217 (8.2%) had three; 57.3% of 1690 FD, 54.6% of 1337 GERD, 82.6% of 328 IBS-C, and 62.5% of 552 CIC respondents had condition overlap. Overall GI symptoms were very/extremely bothersome in 28.6% of single condition respondents, 50.7% of two-condition, and 69.6% of three-condition respondents (p < 0.001, chi square). Symptom frequency and productivity losses both increased with condition overlap. Over 12 months, 43.7% of single-condition, 49.9% of two-condition, and 66.5% of three-condition respondents consulted a physician about GI symptoms (p < 0.001, chi square). CONCLUSION: Functional GI disorders frequently overlap with each other and with GERD. Condition overlap is associated with greater symptom burden and increased physician consultations. PMID- 27403309 TI - Randomized controlled study of endoscopic band ligation and argon plasma coagulation in the treatment of gastric antral and fundal vascular ectasia. AB - BACKGROUND: Gastric antral vascular ectasia (GAVE) is characterized by mucosal and submucosal vascular ectasia causing recurrent hemorrhage and thus, chronic anemia, in patients with cirrhosis. Treatment with argon plasma coagulation (APC) is an effective and safe method, but requires multiple sessions of endoscopic therapy. Endoscopic band ligation (EBL) was found to be a good alternative for APC as a treatment for GAVE, especially in refractory cases. The aim of this prospective randomized controlled study was to evaluate the safety and efficacy of EBL, as compared to APC, in the treatment of GAVE and gastric fundal vascular ectasia (GFVE). PATIENTS AND METHODS: A total of 88 cirrhotic patients with GAVE were prospectively randomized to endoscopic treatment with either EBL or APC, every 2 weeks until complete obliteration was accomplished; then they were followed up endoscopically after 6 months, plus they had monthly measurement of hemoglobin levels during that period. RESULTS: We describe the presence of mucosal and submucosal lesions in the gastric fundal area that were similar to those found in GAVE in 13 patients (29.5%) of the EBL group and 9 patients (20.5%) of the APC group; we named this GFVE. In these cases, we treated the fundal lesions with the same techniques we had used for treating GAVE, according to the randomization. We found that EBL significantly decreased the number of sessions required for complete obliteration of the lesions (2.98 sessions compared to 3.48 sessions in the APC group (p < 0.05)). Hemoglobin levels increased significantly after obliteration of the lesions in both groups, compared to pretreatment values (p < 0.05), but with no significant difference between the two groups (p > 0.05); however, the EBL group of patients required a significantly smaller number of units of blood transfusion than the APC group of patients (p < 0.05). There were no significant differences in adverse events nor complications between the two groups (p > 0.05). CONCLUSIONS: This study described and histologically proved the presence of GFVE occurring comcomitantly with GAVE in cirrhotic patients. We showed that GFVE can be successfully managed by EBL or APC. Our study revealed that EBL is more effective and is comparable in safety to APC, in the treatment of GAVE and GFVE in cirrhotic patients. PMID- 27403310 TI - Prevalence of constipation in the German population - a representative survey (GECCO). AB - BACKGROUND: Variable prevalence rates between 2.4 and 35% have been reported for chronic constipation across different countries worldwide, with a low 5% for Germany. OBJECTIVES AND METHODS: We conducted a computer-assisted telephone interview among 15,002 representative individuals in Germany, asking about health related problems, including constipation. Those who acknowledged the presence of constipation symptoms during the preceding 12 months were questioned concerning constipation features and sociographic variables. RESULTS: Of 15,002 individuals interviewed, 2,239 (14.9%) acknowledged having experienced constipation during the last 12 months, 864 (5.8%) reported constipation during the last 4 weeks, and 380 (2.5%) had current constipation symptoms; 4.4% had taken medication because of their constipation, and 2.6% had consulted a doctor for constipation. In comparison to non-constipated volunteers, those constipated had a lower health quality of life and poorer health, and lower income and social status. CONCLUSION: Up to 15% of the general (German) population report symptoms of constipation depending on the definition. This matches pooled constipation rates across 18 countries (14%). PMID- 27403311 TI - Distribution, size and shape of colorectal adenomas as determined by a colonoscopist with a high lesion detection rate: Influence of age, sex and colonoscopy indication. AB - BACKGROUND: Increasing attention is focused on polyp-related features that may contribute to the operator-dependent nature of colonoscopy. Few data on polyps are available from high-yield colonoscopies, which may serve as a benchmark for quality control. OBJECTIVES: Describe regional distribution, histology, size and shape of polyps, and the influence of patient age and gender, in colonoscopies performed by a colonoscopist with high lesion detection rate. METHODS: Analysis of 698 consecutive patients with diagnostic, screening or surveillance colonoscopies. RESULTS: In 704 colonoscopies, 1908 polyps were removed (360 were protruded and 1548 flat; 1313 were hyperplastic, 562 adenomas, 5 serrated adenomas and 8 mixed). There were 232 adenomas in female patients and 343 in male patients; 39% of the adenomas were protruded and 61% were flat. The peak adenoma detection rate (ADR) was 51% in patients beyond age 79 years. Men older than 49 years had a higher ADR than women. In men and women, respectively: 40% and 32% of adenomas were in the right colon, 31% and 22% were in the transverse colon, and 30% and 47% were in the left colon. Beyond age 59 years, the majority of adenomas were in the proximal colon. CONCLUSIONS: An excess of adenomas in the proximal colon started at age 60 and this was more pronounced in men than in women. In all colonic regions, the majority of adenomas had a shape that was flat and smaller than 6 mm. PMID- 27403312 TI - Characteristics of chronic megacolon among patients diagnosed with multiple endocrine neoplasia type 2B. AB - BACKGROUND: Gastrointestinal symptoms are frequent in multiple endocrine neoplasia (MEN) 2B and may be related to megacolon. OBJECTIVE: The objective of this article is to review the clinical features of patients with MEN 2B, particularly megacolon. METHODS: We used natural language processing of electronic medical records of Mayo Clinic patients over 20 years: Eight patients with definite MEN 2B were identified; of these, four had megacolon. From these patients' records, three others with paper medical records were identified through familial association. We used a standard data sheet to identify features of the disease with particular emphasis on megacolon. RESULTS: Of the 11 patients identified with MEN 2B, seven (63%) had megacolon, typically presenting with constipation in infancy or megacolon in childhood. In addition, three patients had esophageal manifestations (two achalasia and one Zenker's diverticulum). Megacolon often required surgical intervention for intractable constipation, abdominal distension and discomfort. Histopathological features of resected colon revealed enteric and extrinsic nerve hyperplasia and ganglioneuromas of the submucosal and myenteric plexuses. CONCLUSIONS: Among patients with MEN 2B, 63% had megacolon. Significant esophageal motor disorders in MEN 2B may affect ~25% of patients. Any presentation with megacolon should trigger a search for MEN 2B in order to identify the potentially fatal endocrine tumors. PMID- 27403313 TI - The combination of oligo- and polysaccharides and reticulated protein for the control of symptoms in patients with irritable bowel syndrome: Results of a randomised, placebo-controlled, double-blind, parallel group, multicentre clinical trial. AB - BACKGROUND: A medical device containing the film-forming agent reticulated protein and a prebiotic mixture of vegetable oligo- and polysaccharides has been developed, recently receiving European approval as MED class III for the treatment of chronic/functional or recidivant diarrhoea due to different causes including irritable bowel syndrome (IBS). In the present paper, we evaluate a protein preparation containing these components in comparison with placebo in adult patients with diarrhoea-predominant IBS. METHODS: In a randomised, placebo controlled, double-blind, parallel group, multicentre clinical trial, patients were randomly assigned to receive the combination of oligo- and polysaccharides and reticulated protein and placebo (four oral tablets/day for 56 days). Demographic, clinical and quality of life characteristics and presence and intensity of abdominal pain and flatulence (seven-point Likert scale) were assessed at three study visits (baseline and at 28 and 56 days). Stool emissions were recorded on the diary card using the seven-point Bristol Stool Scale. RESULTS: A total of 128 patients were randomised to receive either tablets containing the combination (n = 63) or placebo (n = 65). Treatment with oligo- and polysaccharides and reticulated protein was safe and well tolerated. A significant improvement in symptoms across the study was observed in patients treated with oligo- and polysaccharides and reticulated protein between visit 2 and visit 3 in abdominal pain (p = 0.0167) and flatulence (p = 0.0373). We also detected a statistically significant increase in the quality of life of patients receiving the active treatment from baseline to visit 3 (p < 0.0001). CONCLUSIONS: Treatment with oligo- and polysaccharides and reticulated protein is safe, improving IBS symptoms and quality of life of patients with diarrhoea predominant IBS. PMID- 27403314 TI - Knife-assisted snare resection (KAR) of large and refractory colonic polyps at a Western centre: Feasibility, safety and efficacy study to guide future practice. AB - OBJECTIVE: Endoscopic mucosal resection (EMR) is widely practiced in western countries. Endoscopic submucosal dissection (ESD) is very effective for treating complex polyps but colonic ESD in the western setting remains challenging. We have developed a novel technique of knife-assisted snare resection (KAR) for the resection of these complex lesions. Here we aim to describe the technique, evaluate its outcomes, identify outcome predictors and define its learning curve. METHODS: We conducted a prospective cohort study of patients who had large and refractory polyps resected by KAR at our institution from 2007 to 2013. Polyp characteristics and procedure details were recorded. Endoscopic follow-up was performed to identify recurrence. RESULTS: A total of 170 patients with polyps 20 170 mm in size were treated by KAR and followed up for a mean of 31.5 months (range 12-84 months). 29% of the polyps were >50 mm, 22% had fibrosis from previous unsuccessful interventions and 25% were in the right colon. The perforation rate (1.2%) and bleeding rate (4.7%) were acceptable and managed conservatively in most patients. Recurrence rate after the first attempt was 13.1%. Recurrence was significantly increased by polyp size >50 mm (p = 0.008; OR 5.03, 95% CI 1.54-16.48), presence of fibrosis (p = 0.002; OR 6.59, 95% CI 1.97 22.07) and piecemeal resection (p < 0.001; OR 0.31, CI 0.078-1.12). Cure rates were 87% after the first attempt, improving to 95.6% with further attempts. En bloc resection rate showed a linear increase and reached almost 80% as the endoscopist's cumulative experience approached 100 cases. CONCLUSION: This is the largest reported Western series on KAR in the colon. We have demonstrated the feasibility, efficacy and safety of this technique in the treatment of complex polyps, with or without fibrosis and at all sites. KAR has shown better outcomes than either EMR or ESD. We have also managed to identify significant outcome predictors and define the learning curve. PMID- 27403315 TI - Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: how should rifabutin be managed in rescue regimens? PMID- 27403316 TI - Reply to letter to the editor: "The dosage of rifabutin in H. pylori eradication regimen should be appropriately determined in each area of the world". PMID- 27403317 TI - Cross-border scientific projects run by UEG national member societies reduce health inequalities across Europe. PMID- 27403318 TI - PhDs in academic gastroenterology: key to a successful career. PMID- 27403319 TI - Ultrasound assessment of fascial connectivity in the lower limb during maximal cervical flexion: technical aspects and practical application of automatic tracking. AB - BACKGROUND: The fascia provides and transmits forces for connective tissues, thereby regulating human posture and movement. One way to assess the myofascial interaction is a fascia ultrasound recording. Ultrasound can follow fascial displacement either manually or automatically through two-dimensional (2D) method. One possible method is the iterated Lucas-Kanade Pyramid (LKP) algorithm, which is based on automatic pixel tracking during passive movements in 2D fascial displacement assessments. Until now, the accumulated error over time has not been considered, even though it could be crucial for detecting fascial displacement in low amplitude movements. The aim of this study was to assess displacement of the medial gastrocnemius fascia during cervical spine flexion in a kyphotic posture with the knees extended and ankles at 90 degrees . METHODS: The ultrasound transducer was placed on the extreme dominant belly of the medial gastrocnemius. Displacement was calculated from nine automatically selected tracking points. To determine cervical flexion, an established 2D marker protocol was implemented. Offline pressure sensors were used to synchronize the 2D kinematic data from cervical flexion and deep fascia displacement of the medial gastrocnemius. RESULTS: Fifteen participants performed the cervical flexion task. The basal tracking error was 0.0211 mm. In 66 % of the subjects, a proximal fascial tissue displacement of the fascia above the basal error (0.076 mm +/- 0.006 mm) was measured. Fascia displacement onset during cervical spine flexion was detected over 70 % of the cycle; however, only when detected for more than 80 % of the cycle was displacement considered statistically significant as compared to the first 10 % of the cycle (ANOVA, p < 0.05). CONCLUSION: By using an automated tracking method, the present analyses suggest statistically significant displacement of deep fascia. Further studies are needed to corroborate and fully understand the mechanisms associated with these results. PMID- 27403320 TI - A novel flow cytometric-based method to measure kinase inhibition in sputum from COPD subjects. AB - INTRODUCTION: Janus kinases (JAKs) regulate inflammatory gene expression through phosphorylation of signal transducer and activator of transcription (STAT) proteins. Expression of STAT proteins is increased in chronic obstructive pulmonary disease (COPD), and may be involved in driving chronic inflammation. Oral JAK inhibitors are effective as anti-inflammatory therapy but exhibit dose limiting adverse effects. Development of inhaled compounds would be enhanced by robust biomarkers that directly reflect the anti-inflammatory and pharmacological activity in the lung. METHODS: A novel flow cytometry assay was developed to measure STAT1 phosphorylation in sputum inflammatory cells. The standard sputum processing method was refined to improve sputum cell viability. The flow cytometric assay was used to assess the reproducibility of the measurement of STAT1 phosphorylation and the in vitro activity of a pan JAK-inhibitor on three separate visits in patients with COPD. RESULTS: Upregulation of STAT1 phosphorylation was measured following in vitro IFNgamma stimulation of sputum macrophages (stimulated/unstimulated ratio 1.57; p<0.00001). Upregulation was inhibited following in vitro preincubation with a pan JAK-inhibitor (inhibited+stimulated/unstimulated ratio 0.97). STAT1 phosphorylation activity could only be measured in macrophages. CONCLUSIONS: Sputum from patients with COPD can be used to reproducibly measure phospho-STAT expression in sputum macrophages. The flow cytometry-based method can be used to evaluate kinase inhibitors in vitro and subsequently in ex vivo studies. The assay is particularly useful for the assessment of inhaled compounds where whole blood assays may not be relevant. PMID- 27403321 TI - Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study. AB - BACKGROUND: Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. METHODS: 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. RESULTS: Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). CONCLUSIONS: In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD. PMID- 27403322 TI - The agreement of patient-reported versus observed medication adherence in type 2 diabetes mellitus (T2DM). AB - OBJECTIVE: Medication adherence in type 2 diabetes mellitus (T2DM) improves glycemic control and is associated with reduced adverse clinical events, and accurately assessing adherence assessment is important. We aimed to determine agreement between two commonly used adherence measures-the self-reported Morisky Medication Adherence Scale (MMAS) and direct observation of medication use by nurse practitioners (NPs) during home visits-and determine the relationship between each measure and glycated hemoglobin (HbA1c). RESEARCH DESIGN AND METHODS: We evaluated agreement between adherence measures in the Southeastern Diabetes Initiative (SEDI) prospective clinical intervention home visit cohort, which included high-risk patients (n=430) in 4 SEDI-participating counties. The mean age was 58.7 (SD 11.6) years. The majority were white (n=210, 48.8%), female (n=236, 54.9%), living with a partner (n=316, 74.5%), and insured by Medicare/Medicaid (n=361, 84.0%). Medication adherence was dichotomized to 'adherent' or 'not adherent' using established cut-points. Inter-rater agreement was evaluated using Cohen's kappa coefficient. Relationships among adherence measures and HbA1c were evaluated using the Wilcoxon rank-sum test and c statistics. RESULTS: Fewer patients (n=261, 61%) were considered adherent by self reported MMAS score versus the NP-observed score (n=338; 79%). Inter-rater agreement between the two adherence measures was fair (kappa=0.24; 95% CI 0.15 to 0.33; p<0.0001). Higher adherence was significantly associated with lower HbA1c levels for both measures, yet discrimination was weak (c-statistic=0.6). CONCLUSIONS: Agreement between self-reported versus directly observed medication adherence was lower than expected. Though scores for both adherence measures were significantly associated with HbA1c, neither discriminated well for discrete levels of HbA1c. PMID- 27403323 TI - Physical activity, sedentary behaviors and the incidence of type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: The association between physical activity (PA), sedentary behavior, and incident diabetes has been assessed in whites but is less well investigated in multiethnic populations. OBJECTIVE: To assess the association between PA, sedentary behavior, and incident diabetes in the Multi-Ethnic Study of Atherosclerosis. RESEARCH DESIGN AND METHODS: Incident diabetes was assessed among adults without prevalent baseline diabetes (2000-2002) at 5 in-person examinations between 2002 and 2012. Baseline PA (moderate, vigorous, and exercise specific; metabolic equivalents of task-hours/week) and sedentary behaviors (television watching, reading; hours/day) were assessed by questionnaire. HRs were estimated using Cox proportional hazard models. RESULTS: Among 5829 adults (mean age 61.8 years, 54% female, 42% white, 12% Chinese-American, 26% African American, 21% Hispanic-American), there were 655 incident diabetes cases (median follow-up 11.1 years). After adjustment, diabetes risk was lower in those with brisk or striding compared with none or casual walking pace (HR 0.67; 95% CI 0.54 to 0.84), higher levels of exercise PA (HR for highest vs lowest quartile 0.79; 95% CI 0.63 to 0.98), and any compared with no vigorous PA (HR 0.79; 95% CI 0.66 to 0.95). Race/ethnicity influenced the association of walking pace, exercise PA, and any vigorous PA on diabetes risk, which was only significant among whites. Total leisure sedentary behaviors (HR for highest vs lowest quartile 1.65; 95% CI 1.26 to 2.14) and television watching (HR for highest vs lowest quartile 2.68; 95% CI 1.38 to 5.21) were significantly associated with diabetes risk in multiethnic analyses and were influenced by race/ethnicity. CONCLUSIONS: These results confirm the importance of PA and sedentary behavior on diabetes risk in a multiethnic population and demonstrate potential variations across race/ethnic groups. PMID- 27403324 TI - Ethnic differences in prediabetes and diabetes in the Suriname Health Study. AB - BACKGROUND: Diabetes is increasing worldwide, and information on risk factors to develop targeted interventions is limited. Therefore, we analyzed data of the Suriname Health Study to estimate the prevalence of prediabetes and diabetes. We also explored whether ethnic differences in prediabetes or diabetes risk could be explained by biological, demographic, lifestyle, anthropometric, and metabolic risk factors. METHOD: The study was designed according to the WHO Steps guidelines. Fasting blood glucose levels were measured in 3393 respondents, aged 15-65 years, from an Amerindian, Creole, Hindustani, Javanese, Maroon or Mixed ethnic background. Prediabetes was defined by fasting blood glucose levels between 6.1 and 7.0 mmol/L and diabetes by fasting blood glucose levels >=7.0 mmol/L or 'self-reported diabetes medication use.' For all ethnicities, we analyzed sex, age, marital status, educational level, income status, employment, smoking status, residence, physical activity, body mass index, waist circumference, hypertension, and the levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol. RESULTS: The prevalence of prediabetes was 7.4%, while that of diabetes was 13 0%. From these diabetes cases, 39.6% were not diagnosed previously. No ethnic differences were observed in the prevalence of prediabetes. For diabetes, Hindustanis (23.3%) had twice the prevalence compared to other ethnic groups (4.7 14.2%). The associations of the risk factors with prediabetes or diabetes varied among the ethnic groups. The differences in the associations of ethnic groups with prediabetes or diabetes were partly explained by these risk factors. CONCLUSIONS: The prevalence of diabetes in Suriname is high and most elevated in Hindustanis. The observed variations in risk factors among ethnic groups might explain the ethnic differences between these groups, but follow-up studies are needed to explore this in more depth. PMID- 27403325 TI - Psychological barriers to optimal insulin therapy: more concerns in adolescent females than males. AB - OBJECTIVE: The aim of this study is to investigate psychological barriers (illness perceptions, insulin beliefs, and coping strategies) to optimal insulin therapy among adolescents with type 1 diabetes (T1D), with a specific focus on gender differences and mode of treatment (insulin pump vs pen). METHODS: A total of 105 males and females (12-20 years) participated in this study. The Brief Illness Perception Questionnaire, the Beliefs about Medicines Questionnaire, and the Adolescent Coping Orientation for Problem Experiences were completed. Additionally, diabetes clinical data were collected by the Norwegian Childhood Diabetes Registry. RESULTS: Females had significantly more negative illness perceptions than males on all dimensions (p<0.05), with moderate-to-large effect sizes. Regarding insulin beliefs, females scored significantly higher than males on insulin concern (p<0.001), indicating more concerns about insulin. There were no significant gender differences on perceptions of insulin necessity. Finally, females scored significantly higher on the coping strategies being social and solving family problems (p<0.01), indicating more positive coping among females than males for these subscales. In terms of treatment mode, the only statistically significant difference in the psychological aspects was for the illness perception treatment control, with patients using insulin pen reporting more negative perceptions on this dimension than patients using insulin pump. CONCLUSIONS: Addressing psychological aspects may be a clinically important supplement to standard somatic T1D care. The consistent finding of gender differences across the psychological measures implies that a tailored treatment approach for males and females with T1D may be warranted. PMID- 27403326 TI - Impact of sex and age on the performance of FINDRISC: the HUNT Study in Norway. AB - OBJECTIVE: The Finnish Diabetes Risk Score (FINDRISC) is recommended as a screening tool for diabetes risk. However, there is a lack of well-powered studies examining the performance of FINDRISC by sex and age. We aim to estimate, by sex and age, the prevalence of elevated FINDRISC and positive predictive value (PPV) of FINDRISC for identifying impaired glucose metabolism (IGM) in a general Norwegian population. RESEARCH DESIGN AND METHODS: We estimated the prevalence of elevated FINDRISC (>=15) among 47 694 adults in the third survey of the Nord Trondelag Health Study (HUNT3, 2006-08). Among 2559 participants who participated in oral glucose tolerance testing, we estimated the PPV of elevated FINDRISC for identifying unknown prevalent diabetes and other forms of IGM. RESULTS: The prevalence of elevated FINDRISC was 12.1% in women, 9.6% in men, and increased from 1.5% at age 20-39 to 25.1% at age 70-79 years. The PPVs of elevated FINDRISC were 9.8% for diabetes, 16.9% for impaired glucose tolerance, 8.2% for impaired fasting glucose, and 34.9% for any form of IGM. The PPV for IGM was lower in women (31.2%) than in men (40.4%), and increased from 19.1% at age 20-39 to 55.5% at age >=80 years. CONCLUSIONS: FINDRISC identified more women than men as high risk individuals for diabetes. FINDRISC had a high PPV for detecting prevalent IGM, and the PPV was higher in men than in women and in the older individuals. Our data indicate that the impact of sex and age on diabetes risk is not fully captured by FINDRISC, and that refinements to it might improve diabetes prediction. PMID- 27403327 TI - H9N2 low pathogenic avian influenza in Pakistan (2012-2015). AB - Significant economic losses from deaths and decreased egg production have resulted from H9N2 low pathogenic avian influenza virus (LPAIV) infections in poultry across North Africa, the Middle East and Asia. The H9N2 LPAIVs have been endemic in Pakistani poultry since 1996, but no new viruses have been reported since 2010. Because novel genotypes of Pakistani H9N2 contain mammalian host specific markers, recent surveillance is essential to better understand any continuing public health risk. Here the authors report on four new H9N2 LPAIVs, three from 2015 and one from 2012. All of the viruses tested in this study belonged to Middle East B genetic group of G1 lineage and had PAKSSR/G motif at the haemagglutinin cleavage site. The mammalian host-specific markers at position 226 in the haemagglutinin receptor-binding site and internal genes suggest that Pakistan H9N2 viruses are still potentially infectious for mammals. Continued active surveillance in poultry and mammals is needed to monitor the spread and understand the potential for zoonotic infection by these H9N2 LPAIVs. PMID- 27403328 TI - Evaluation of quality of life of carers of Italian spinoni with idiopathic epilepsy. AB - The carers of all UK Kennel Club registered Italian spinoni (IS) born between January 1, 2000 and December 31, 2011 were invited to participate in the study. The carers of 47 of 63 IS diagnosed with idiopathic epilepsy (IE) returned the questionnaire, which included numerous questions on various aspects of IE including the effect of IE on the dog's carer's quality of life. Median epileptic seizure number in the three months before study end or death was five epileptic seizures, 72 per cent of dogs had cluster seizures, 94 per cent of dogs were administered one or more antiepileptic medications and 36 per cent of dogs were euthanased due to poorly controlled IE. Seventy-one per cent and 65 per cent of the participants were moderately to extremely worried about the frequency and severity of their dog's epileptic seizures, respectively. Caring for an IS with IE caused conflict with the carer's work, education or daily activity often or very often in 50 per cent of the participants. Overall the limitations on the carer's life due to caring for an IS with IE were considered as very to extremely bothersome in 29 per cent of the participants, a little to moderately bothersome in 40 per cent of the participants and not at all bothersome in 31 per cent of the participants. PMID- 27403329 TI - Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study. AB - OBJECTIVES: To explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements. METHODS: Cardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin. RESULTS: The CFS group length of history (mean+/-SD) was 14+/-10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean+/-SD RCV was 1565+/-443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659+/-529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r(2)=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r(2)=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities. CONCLUSIONS: This study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS. PMID- 27403331 TI - Staged re-evaluation of non-culprit lesions in ST segment elevation myocardial infarction: a retrospective study. AB - OBJECTIVE: It remains unknown whether complete revascularisation is optimally performed in patients with ST segment elevation myocardial infarction (STEMI) during the index or at staged procedures. The aims of this study were to quantify the number of primary percutaneous coronary intervention (PCI) procedures in which non-culprit lesions needed further evaluation, to determine the consequence of the re-evaluation and to quantify adverse cardiac events during the waiting time for re-evaluation and intervention. METHODS: The study was observational and retrospective and included all patients with STEMI treated with primary PCI during 1 year at our centre. RESULTS: Among the 507 patients with STEMI, 374 were considered sufficiently treated with culprit lesion PCI only. Complete primary multivessel revascularisation was performed in 11 patients. Non-culprit lesion re evaluation was planned for 122 patients (24%). Of these 122 patients, 3 patients died during their index admission. Follow-up data were not available for 3 patients. Among the 116 patients, 187 non-culprit lesions were re-evaluated and 77 patients (66.4%) underwent revascularisation with treatment of 119 lesions (63.3%). Re-evaluation was performed after a median of 30 days (25th centile: 9 days, 75th centile: 35 days). During the waiting time for re-evaluation, two patients underwent a new primary PCI due to stent thrombosis of the index culprit lesion. CONCLUSIONS: Staged re-evaluation of non-culprit lesions observed in patients with STEMI was required in 24% of a primary PCI cohort. Intervention was performed in 66.4% of patients scheduled for re-evaluation. We observed no adverse events related to the non-culprit lesions during the waiting time for a staged re-evaluation or intervention. PMID- 27403330 TI - Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events. AB - OBJECTIVE: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. METHODS: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. RESULTS: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). CONCLUSIONS: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. TRIAL REGISTRATION NUMBER: UMIN000001932; Results. PMID- 27403332 TI - Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE. AB - OBJECTIVE: The Sydney classification criteria for antiphospholipid syndrome include lupus anticoagulant or moderate-to-high titre anticardiolipin IgG or IgM. We explored the association of all anticardiolipin isotypes, lupus anticoagulant and the combination with venous and arterial thrombosis. METHODS: Patients with systemic lupus erythematosus (SLE) in a large clinical cohort seen quarterly were repeatedly tested by protocol for anticardiolipin antibodies and lupus anticoagulant. Subgroups of patients were defined based on the geometric mean titres of IgG, IgM, IgA anticardiolipin and lupus anticoagulant expressed in dilute Russell's viper venom time (RVVT) seconds for each patient across all cohort visits. These subgroups were compared with respect rates of thrombosis since diagnosis with SLE. Rate ratios were estimated using Cox Proportional Hazards models. RESULTS: Of the 1390 cohort members included, there were 284 thrombotic events observed over 17 025 person-years since diagnosis for a rate of 1.7 events per 100 person-years. Those with a geometric mean titre of IgG anticardiolipin >20 had a significantly elevated rate of thromboses (rate ratio 1.8, p=0.0052), whereas there was no evidence of an association between thromboses and elevated IgM geometric mean (rate ratio 1.2, p=0.40). There were relatively few cohort members with elevated IgA geometric mean but the rate of thromboses in that group was elevated (rate ratio 1.7, p=0.23). The associations between anticardiolipin antibodies and thromboses were strongest when considering venous thromboses. Those with two or more elevated anticardiolipin isotypes or those with both IgG anticardiolipin and RVVT did not appear at higher risk than those with a single elevated marker. CONCLUSION: This study supports previous observations that IgG anticardiolipin and lupus anticoagulant are associated with higher rates of thromboses. Our power to study IgA anticardiolipin was limited due to small number of patients with elevated IgA. PMID- 27403333 TI - Automatic behavior and communication due to pramipexole. AB - A 45-year-old woman reported automatic behaviors and communication whilst she was being treated with pramipexole. These episodes vanished after the medication was tapered and she was started on levodopa/carbidopa. I hypothesize that the episodes were related to disordered awareness due to sleep disruption related to this medication. PMID- 27403334 TI - Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis. AB - BACKGROUND: Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ~50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more 'evidence-based biological therapy'. OBJECTIVES: Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. METHODS: CZP was conjugated with succinimidyl-6-hydrazino nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. RESULTS: In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). CONCLUSIONS: Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response. TRIAL REGISTRATION NUMBER: NCT01590966; Results. PMID- 27403335 TI - Characteristics of rheumatoid arthritis and its association with major comorbid conditions: cross-sectional study of 502 649 UK Biobank participants. AB - INTRODUCTION: To characterise the detailed phenotypic and comorbid characteristics of participants with rheumatoid arthritis (RA) in the large population-based UK Biobank, thereby enabling future longitudinal analyses. METHODS: We undertook a cross-sectional study using baseline data from the unique UK Biobank resource (n=502 649). RA was based on self-report, and type of medication was used as a proxy measure of valid diagnosis. Participants with and without RA were compared in terms of sociodemographic, lifestyle and other disease-related risk factors. Logistic regression models were used to determine whether participants with RA were more likely to report comorbid conditions, and whether this varied by RA severity. The models were adjusted for potential confounders and lifestyle risk factors. RESULTS: At baseline, 5657 (1.13%) eligible UK Biobank participants reported RA of whom 2849 (0.57%) had medically treated RA (median duration=10 years). Prevalence was significantly higher among female, South Asian and socioeconomically deprived participants. Participants with RA were significantly more likely to report diabetes (covariate-adjusted OR 1.18, 95% CI 1.06 to 1.32, p<0.01), hypertension (OR 1.19, 95% CI 1.21 to 1.27, p<0.001) and cardiovascular disease (OR 1.52, 95% CI 1.39 to 1.67, p<0.001). CONCLUSIONS: UK Biobank provides extensive data concerning RA population-level comorbidity and risk factors. The frequency, distribution and characteristics of participants reporting RA in UK Biobank are largely consistent with other studies. It provides a unique opportunity to interrogate biomarkers, genetic data, detailed imaging and linkage to clinical records at the population level across primary and secondary care. PMID- 27403336 TI - Does body mass index (BMI) influence the Ankylosing Spondylitis Disease Activity Score in axial spondyloarthritis?: Data from the SPACE cohort. AB - OBJECTIVE: Obesity is associated with elevated C reactive protein (CRP) levels. The Ankylosing Spondylitis Disease Activity Score (ASDAS) combines patient reported outcomes (PROs) and CRP. We evaluated the effect of body mass index (BMI) on CRP and on ASDAS, and studied if ASDAS can be used in obese axial spondyloarthritis (axSpA) patients to assess disease activity. METHODS: Baseline data of patients with chronic back pain of short duration included in the SPondyloArthritis Caught Early (SPACE) cohort were used. Collected data included BMI and ASDAS. Patients were classified according to the ASAS axSpA classification criteria and BMI (overweight >=25 and obese >=30). Correlation and linear regression analyses were performed to assess the relation between BMI and ASDAS. Linear regression models were performed to assess if age or gender were effect modifiers in the relation between BMI and CRP, and between BMI and ASDAS. RESULTS: In total, 428 patients were analysed (n=168 axSpA; n=260 no-axSpA). The mean age was 31.1 years, 36.9% were male, 26.4% were overweight and 13.3% obese, median CRP was 3 mg/L and the mean ASDAS was 2.6. Gender was the only factor modifying the relationship between BMI and CRP as BMI had an influence on CRP only in females (beta=0.35; p<0.001). Correlations between BMI and CRP or PROs were generally weak, and only significant for CRP in female patients. BMI was not related to ASDAS in axSpA patients. CONCLUSIONS: ASDAS is not affected by BMI in axSpA patients. Therefore, based on our data it is not necessary to take BMI in consideration when assessing disease activity using ASDAS in axSpA patients. PMID- 27403337 TI - Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation. AB - Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods. We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma. Results. Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P < 0.001). There was no significant difference between groups regarding patient survival; 5 year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P = 0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P = 0.016). Conclusions. iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC. PMID- 27403338 TI - Evaluation of Choroidal Thickness in Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma. AB - Purpose. To compare the macular and peripapillary choroidal thickness in eyes with pseudoexfoliation (PEX) syndrome and PEX glaucoma with the normal eyes of healthy controls. Materials and Methods. In this prospective study, 30 eyes of 30 patients with PEX syndrome, 28 eyes of 28 patients with PEX glaucoma, and 30 eyes of 30 age-matched healthy subjects were enrolled. Choroidal thicknesses in the macular and peripapillary areas were measured by using spectral domain optical coherence tomography. Results. Gender, age, and axial length did not significantly differ between the groups (all, p > 0.05). The mean values of choroidal thickness in the macular and peripapillary areas (except the superior quadrant) in the patients with PEX syndrome and PEX glaucoma were lower compared with controls (all p < 0.05). The mean values of the macular and peripapillary choroidal thickness in the PEX glaucoma group were lower compared with PEX syndrome group; however this difference was not significant. Conclusions. The findings of this study revealed that macular and peripapillary choroidal thicknesses were decreased in PEX syndrome and PEX glaucoma cases. The role of choroid in the development of glaucomatous damage in patients with PEX syndrome remains unclear. PMID- 27403339 TI - Comparison between a New Optical Biometry Device and an Anterior Segment Optical Coherence Tomographer for Measuring Central Corneal Thickness and Anterior Chamber Depth. AB - Purpose. To compare between a new optical biometer (AL-Scan, Nidek Co., Aichi, Japan) and an anterior segment optical coherence tomographer (Visante AS-OCT, Carl Zeiss Meditec, Dublin, USA) for measuring central corneal thickness (CCT), anterior chamber depth (ACD), and aqueous depth (AD). Methods. Sixty-three eyes of 63 normal subjects were examined with AL-Scan and Visante AS-OCT in this prospective study. One eye per subject was measured three times with both devices to record their CCT, ACD, and AD. All procedures were performed by the same operator. Agreement between the two devices was assessed using paired t-tests, Bland-Altman plots, and 95% limits of agreement (LoA). Results. The mean CCT, ACD, and AD measured by AL-Scan were 538.59 +/- 27.37 MUm, 3.70 +/- 0.30 mm, and 3.16 +/- 0.30 mm, respectively. The mean values obtained by the Visante OCT were 536.14 +/- 26.61 MUm for CCT, 3.71 +/- 0.29 mm for ACD, and 3.17 +/- 0.29 mm for AD. The mean CCT by the AL-Scan was higher than that obtained by the Visante AS OCT (difference = 2.45 +/- 6.07 MUm, P < 0.05). The differences in ACD and AD measurements were not statistically significant. The 95% LoA of CCT, ACD, and AD were between -9.44 and 14.35 MUm, -0.15 and 0.12 mm, and -0.15 and 0.12 mm, respectively. Conclusions. Since these two devices were comparable for measuring CCT, ACD, and AD, their results can be interchangeably used in the clinic. PMID- 27403340 TI - Subclinical Posttraumatic Stress Disorder Symptoms: Relationships with Blood Pressure, Hostility, and Sleep. AB - The purpose of this study was to examine the relationships among subclinical PTSD symptoms, blood pressure, and several variables linked to both frank PTSD and the basic psychobiological adaptation to stress. The authors recruited a sample of 91 healthy, young men and women between 18 and 35 years. We examined links among subclinical posttraumatic stress disorder symptoms, blood pressure, sleep quality, and hostility. Posttraumatic stress disorder symptoms were associated with poorer sleep quality and higher hostility scores in both women and men. In men, PTSD symptoms were also associated with elevated resting diastolic blood pressure, and sex was an important moderator of that relationship. Moreover, sleep quality and hostility are substantive mediators of the relationship between diastolic blood pressure and PTSD. Behavioral interventions designed to increase sleep quality and restructure hostile attitudes could potentially serve as preventive interventions for PTSD and the underlying cardiovascular comorbidities in young adults. PMID- 27403341 TI - A Qualitative Study to Examine Perceptions and Barriers to Appropriate Gestational Weight Gain among Participants in the Special Supplemental Nutrition Program for Women Infants and Children Program. AB - Women of reproductive age are particularly at risk of obesity because of excessive gestational weight gain (GWG) and postpartum weight retention, resulting in poor health outcomes for both mothers and infants. The purpose of this qualitative study was to examine perceptions and barriers to GWG among low income women in the WIC program to inform the development of an intervention study. Eleven focus groups were conducted and stratified by ethnicity, and each group included women of varying age, parity, and prepregnancy BMI ranges. Participants reported receiving pressure from spouse and family members to "eat for two" among multiple barriers to appropriate weight gain during pregnancy. Participants were concerned about gaining too much weight but had minimal knowledge of weight gain goals during pregnancy. Receiving regular weight monitoring was reported, but participants had inconsistent discussions about weight gain with healthcare providers. Most were not aware of the IOM guidelines nor the fact that gestational weight gain goals differed by prepregnancy weight status. Results of these focus groups analyses informed the design of a pregnancy weight tracker and accompanying educational handout for use in an intervention study. These findings suggest an important opportunity for GWG education in all settings where pregnant women are seen. PMID- 27403342 TI - Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C. AB - Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C. PMID- 27403343 TI - Prevalence of Overweight and Obesity among Primary School Children Aged 8-13 Years in Dar es Salaam City, Tanzania. AB - Background. The understanding of obesity as a growing health problem in Africa and Tanzania in particular is hampered by lack of data as well as sociocultural beliefs in which overweight and obesity are revered. This study sought to determine the prevalence of overweight and obesity among primary school children aged 8-13 years in Dar es Salaam, Tanzania. Method. A cross-sectional analytical research design was used to study overweight and obesity in primary schools in Dar es Salaam, Tanzania. The target population was 150,000 children aged 8-13 years. Stratified random sampling was used to select 1781 children. Weight and height were taken and WHO standards for children were used to determine weight status. Results. Findings showed that the prevalence of overweight and obesity was 15.9% and 6.7%, respectively (N = 1781). However, 6.2% of the children were underweight. There were significant differences in mean BMI between children in private and public schools (p = 0.021), between male and female (p < 0.001), and across age groups of 8-10 and 11-13 years (p < 0.001). Conclusion. The prevalence of overweight and obesity among primary school children is significant and requires management and prevention strategies. PMID- 27403344 TI - Exploiting Interlimb Arm and Leg Connections for Walking Rehabilitation: A Training Intervention in Stroke. AB - Rhythmic arm and leg (A&L) movements share common elements of neural control. The extent to which A&L cycling training can lead to training adaptations which transfer to improved walking function remains untested. The purpose of this study was to test the efficacy of A&L cycling training as a modality to improve locomotor function after stroke. Nineteen chronic stroke (>six months) participants were recruited and performed 30 minutes of A&L cycling training three times a week for five weeks. Changes in walking function were assessed with (1) clinical tests; (2) strength during isometric contractions; and (3) treadmill walking performance and cutaneous reflex modulation. A multiple baseline (3 pretests) within-subject control design was used. Data show that A&L cycling training improved clinical walking status increased strength by ~25%, improved modulation of muscle activity by ~25%, increased range of motion by ~20%, decreased stride duration, increased frequency, and improved modulation of cutaneous reflexes during treadmill walking. On most variables, the majority of participants showed a significant improvement in walking ability. These results suggest that exploiting arm and leg connections with A&L cycling training, an accessible and cost-effective training modality, could be used to improve walking ability after stroke. PMID- 27403345 TI - Training-Induced Functional Gains following SCI. AB - We previously demonstrated that daily, hour-long training sessions significantly improved both locomotor (limb kinematics, gait, and hindlimb flexor-extensor bursting patterns) and nonlocomotor (bladder function and at-level mechanical allodynia) functions following a moderate contusive spinal cord injury. The amount of training needed to achieve this recovery is unknown. Furthermore, whether this recovery is induced primarily by neuronal activity below the lesion or other aspects related to general exercise is unclear. Therefore, the current study objectives were to (1) test the efficacy of 30 minutes of step training for recovery following a clinically relevant contusion injury in male Wistar rats and (2) test the efficacy of training without hindlimb engagement. The results indicate that as little as 30 minutes of step training six days per week enhances overground locomotion in male rats with contusive spinal cord injury but does not alter allodynia or bladder function. Thirty minutes of forelimb-only exercise did not alter locomotion, allodynia, or bladder function, and neither training protocol altered the amount of in-cage activity. Taken together, locomotor improvements were facilitated by hindlimb step training for 30 minutes, but longer durations of training are required to affect nonlocomotor systems. PMID- 27403346 TI - Electrical Stimulation of the Ear, Head, Cranial Nerve, or Cortex for the Treatment of Tinnitus: A Scoping Review. AB - Tinnitus is defined as the perception of sound in the absence of an external source. It is often associated with hearing loss and is thought to result from abnormal neural activity at some point or points in the auditory pathway, which is incorrectly interpreted by the brain as an actual sound. Neurostimulation therapies therefore, which interfere on some level with that abnormal activity, are a logical approach to treatment. For tinnitus, where the pathological neuronal activity might be associated with auditory and other areas of the brain, interventions using electromagnetic, electrical, or acoustic stimuli separately, or paired electrical and acoustic stimuli, have been proposed as treatments. Neurostimulation therapies should modulate neural activity to deliver a permanent reduction in tinnitus percept by driving the neuroplastic changes necessary to interrupt abnormal levels of oscillatory cortical activity and restore typical levels of activity. This change in activity should alter or interrupt the tinnitus percept (reduction or extinction) making it less bothersome. Here we review developments in therapies involving electrical stimulation of the ear, head, cranial nerve, or cortex in the treatment of tinnitus which demonstrably, or are hypothesised to, interrupt pathological neuronal activity in the cortex associated with tinnitus. PMID- 27403347 TI - Respiratory Changes in Response to Cognitive Load: A Systematic Review. AB - When people focus attention or carry out a demanding task, their breathing changes. But which parameters of respiration vary exactly and can respiration reliably be used as an index of cognitive load? These questions are addressed in the present systematic review of empirical studies investigating respiratory behavior in response to cognitive load. Most reviewed studies were restricted to time and volume parameters while less established, yet meaningful parameters such as respiratory variability have rarely been investigated. The available results show that respiratory behavior generally reflects cognitive processing and that distinct parameters differ in sensitivity: While mentally demanding episodes are clearly marked by faster breathing and higher minute ventilation, respiratory amplitude appears to remain rather stable. The present findings further indicate that total variability in respiratory rate is not systematically affected by cognitive load whereas the correlated fraction decreases. In addition, we found that cognitive load may lead to overbreathing as indicated by decreased end-tidal CO2 but is also accompanied by elevated oxygen consumption and CO2 release. However, additional research is needed to validate the findings on respiratory variability and gas exchange measures. We conclude by outlining recommendations for future research to increase the current understanding of respiration under cognitive load. PMID- 27403349 TI - Extremely Rare Form of Impaction Bilateral Kissing Molars: Report of a Case and Review of the Literature. AB - Kissing molars (KM) or rosette formation is a term that is used to describe impacted teeth contacting occlusal surfaces in a single follicular space and their roots pointing in opposite directions. In some cases kissing molars can be seen but occurrence of bilateral kissing molars is extremely rare phenomenon in the dental literature and the aetiology of this phenomenon is still unknown. In this paper we describe a case and review of the literature and discuss the management of this pathology. In our case, extremely rare form of impacted bilateral kissing molars was extracted surgically. The decision of extraction of asymptomatic kissing molars represents surgical dilemma. There may be many surgical complications; on the other hand in some cases surgical intervention is unavoidable. Few treatment options were described in the literature. This phenomenon can be sign of various medical conditions that may require further investigation. In this paper, our treatment option is in agreement with the literature suggesting the surgical removal of both teeth at either side of the mandible. PMID- 27403350 TI - Early Loaded Single Implant Reinforced Mandibular Overdenture. AB - Rehabilitating atrophied mandible with two-implant supported denture is a common treatment modality for implant retained removable overdenture in mandible. This paper aims to design a treatment modality where single implant reinforced overdenture is fabricated for a severely atrophied mandibular ridge with early loading protocol. Results of studies have shown that a single implant mandibular overdenture significantly increases the satisfaction and quality of life of patients with edentulism. Midline fracture of the prosthesis is the most common complication related to single implant and two-implant retained mandibular overdentures. To manage such complication, a thin metal mesh is used to reinforce the overdenture and also to make the prostheses lighter and cost effective as compared to conventional cast metal framework. PMID- 27403351 TI - A Review and Report of Peripheral Giant Cell Granuloma in a 4-Year-Old Child. AB - Peripheral giant cell granuloma is a common benign and reactive gingival epulis in oral cavity. It is often difficult to make a clinical diagnosis; thereby definitive diagnosis depends on histopathologic features. We report a case of a 4 year-old Caucasian boy presenting with a five-month history a 20 * 15 * 12 mm pedunculated, lobular soft tissue mass of the left anterior maxilla gingiva which was misdiagnosed and maltreated before his referral. An excisional biopsy of the lesion followed by histopathologic examination of the biopsy specimen revealed distinctive features of peripheral giant cell granuloma. Early detection and excision of this hyperplastic nodule especially in children are important to minimize potential dentoalveolar complications. PMID- 27403352 TI - Familial Pemphigus Vulgaris Occured in a Father and Son as the First Confirmed Cases. AB - Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease of the skin and mucous membranes. Although there is some evidence pointing towards a genetic predisposition by some human leukocyte antigen (HLA) genes, familial occurrence of PV is very rare. Most of the familial PV cases so far reported have been in mother and daughter and in siblings. PV in father and son, as presented here, has not been reported in the literature before, except an unconfirmed report. The diagnosis of PV was established by histologic, cytologic studies and enzyme linked immunosorbent assay (ELISA) in Case 1 and by ELISA and BIOCHIP indirect immunofluorescence test in Case 2. The son was responsive to moderate doses of methylprednisolone, with the treatment continuing with tapered doses. The father was in a subclinic condition; consequently, only close follow-up was recommended. HLA typing studies revealed identical HLA alleles of HLA-DR4 (DRB1(*)04) and HLA DQB1(*)03 in both of our cases; this had been found to be associated with PV in prior studies. Familial occurrences of PV and related HLA genes indicate the importance of genetic predisposition. The first occurrence of confirmed familial PV in father and son is reported here. PMID- 27403348 TI - The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity. AB - The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin- (SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin (PV-) and vasoactive intestinal peptide- (VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning. PMID- 27403353 TI - Gastrointestinal Pyogenic Granuloma (Lobular Capillary Hemangioma): An Underrecognized Entity Causing Iron Deficiency Anemia. AB - Pyogenic granuloma (PG), more accurately known as lobular capillary hemangioma, is a benign vascular tumor that usually occurs in the skin or oral mucosa. This lesion is rarely reported in the gastrointestinal tract but is known to bleed if not resected. We herein describe a case series with the clinical, endoscopic, and histologic findings of four cases of gastrointestinal PG at our institution. In addition, we provide a review of the literature and summation of all reported cases of PG specific to the gastrointestinal tract. Based on our experience, we suggest that the actual incidence of gastrointestinal PG may in fact be higher than reported because PG can be unrecognized or improperly diagnosed. It is important for the clinician to properly recognize this lesion as a source of anemia and its propensity to bleed during biopsy or resection. PMID- 27403354 TI - A Case of Primary Hepatic Lymphoma and Related Literature Review. AB - Objective. Primary hepatic lymphoma is a rare disease. And the clinical manifestations of this disease are nonspecific. The objective of this paper is to improve clinicians' understanding of this disease. Methods. We analyzed the clinical characteristics of a case of primary hepatic lymphoma in association with hepatitis B virus infection and reviewed the literature. Conclusion. The clinical manifestations of primary hepatic lymphoma are nonspecific. And it is easily misdiagnosed. Postoperative radiotherapy of patients with early stage was previously speculated to achieve favorable improvement. The application of targeted therapeutic drugs, chemotherapy, or combined local radiotherapy has become the first-line treatment strategy. PMID- 27403355 TI - Abnormal TREC-Based Newborn Screening Test in a Premature Neonate with Massive Perivillous Fibrin Deposition of the Placenta. AB - Severe combined immunodeficiency (SCID), a primary immunodeficiency arising from variable defects in lymphocyte development and survival, is characterized by significant deficiency of thymus derived (T-) lymphocytes and variable defects in the B-lymphocyte population. Newborn screening for SCID is based on detection of low numbers of T-cell receptor excision circles (TRECs) by real time quantitative PCR (RT-qPCR). This screening allows for early identification of individuals with SCID and other disorders characterized by T-lymphopenia. Higher rates of abnormal screens are commonly seen in premature and critically ill neonates, often representing false positives. It is possible that many abnormal screens seen in these populations are result of conditions that are characterized by systemic inflammation or stress, possibly in the context of stress-induced thymic involution. We present a case of a male infant delivered at 27 weeks, 6 days of gestation, with severe intrauterine growth restriction who had an abnormal TREC screen and a massive perivillous fibrin deposition (MPFD) of the placenta. This association has not been reported previously. We are raising the awareness to the fact that conditions, such as MPFD, that can create adverse intrauterine environment are capable of causing severe stress-induced thymic involution of the fetus which can present with abnormal TREC results on newborn screening. PMID- 27403356 TI - Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation. AB - Voriconazole is an established first-line agent for treatment of invasive fungal infections in patients undergoing allogeneic stem cell transplantation (ASCT). It is associated with the uncommon complication of periostitis. We report this complication in a 58-year-old female undergoing HSCT. She was treated with corticosteroids with minimal improvement. The symptoms related to periostitis can mimic chronic graft-versus-host disease in patients undergoing HSCT and clinicians should differentiate this from other diagnoses and promptly discontinue therapy. PMID- 27403357 TI - Collapsing Glomerulopathy in a Child with Galloway-Mowat Syndrome. AB - Galloway-Mowat syndrome (GMS) is an autosomal recessive disorder with a poor prognosis that was first defined as a triad of central nervous system involvement, hiatal hernia, and nephrotic syndrome. However, this syndrome is now known to have a heterogeneous clinical presentation. The nephrotic syndrome is steroid resistant and is responsible for the outcome. The combination of collapsing glomerulopathy and GMS is very rare. A 26-month-old boy presented with steroid-resistant nephrotic syndrome associated with neurologic findings, including microcephaly, psychomotor retardation, and nystagmus. Magnetic resonance imaging showed marked cerebral atrophy, optic atrophy, and hypomyelination. A renal biopsy was consistent with collapsing glomerulopathy. If collapsing glomerulopathy is associated with neurological abnormalities, especially with microcephaly, clinicians should consider GMS as a possible underlying cause. PMID- 27403358 TI - Lesion in Scalp and Skull as the First Manifestation of Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the fifth most common cancer in the world. The lungs, bone, and lymph nodes are frequent sites of metastasis of HCC. The purpose of the present study is show that metastases, although rare, must be among the differential diagnosis of skin lesions and that a diagnostic research based on these findings can be conducted. The authors report a rare case of metastatic hepatocellular injury to the scalp and skull treated by a radical surgical approach. Excision of the lesion in the scalp was performed "en bloc." The tumor was supplied by the frontal branch of the superficial temporal artery. There are few case reports of metastatic HCC to scalp and skull; treatment of these lesions should be individualized in order to control symptoms, improve quality of life, and promote an increase in survival. PMID- 27403359 TI - Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barre Syndrome. AB - We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barre syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID- 27403360 TI - Arteriovenous Fistula Embolization in Suspected Parauterine Choriocarcinoma. AB - This is a case of choriocarcinoma that did not regress after chemotherapy treatment. A 30-year-old female patient (gravida 2, para 2), presented to our ER with stroke and persistent mild pelvic pain 2 months after a Caesarean section. Computed tomography (CT) revealed an ischemic left hemicerebellar region and a hypervascular mass in the pelvic region. This mass was not present on routine fetal ultrasound during pregnancy. The lesion was treated by chemotherapy after closure of a foramen ovale and insertion of an inferior vena cava (IVC) filter. After that, 2 courses of EMACO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine) chemotherapy regimen were given. Posttreatment CT showed the hypervascular mass without any changes. Arteriography showed the arteriovenous fistulae that were embolized successfully with plugs, coils, and glue. Embolization was considered due to the risk of acute hemorrhagic life threatening complications. Eight chemotherapy courses were added after embolization. Treatment by endovascular approach and reduction of the hypervascular mass can be a valuable adjunct to chemotherapy treatment of choriocarcinoma. PMID- 27403361 TI - Atypical Proliferating Trichilemmal Cyst with Malignant Breast Skin Transformation: A Case Report and Review of the Literature. AB - Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39 year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided. PMID- 27403362 TI - The Value of Cytology Smears for Acanthamoeba Keratitis. AB - Purpose. Acanthamoeba keratitis remains a difficult diagnosis despite advances in genetic and imaging technologies. The purpose of this paper is to highlight the utility of cytology smears for diagnosis of Acanthamoeba keratitis. Methods. This is a case study of the diagnostic course for a patient with suspected Acanthamoeba keratitis. Results. A 40-year-old male with poor contact lens hygiene presented with severe left eye pain. Slit lamp examination showed two peripheral ring infiltrates without an epithelial defect. The epithelium over both infiltrates was removed with a Kimura spatula. Half of the sample was smeared on a dry microscope slide and the other half was submitted for Acanthamoeba culture and PCR. Both culture and PCR were negative for Acanthamoeba, but hematoxylin and eosin stain of the smear revealed double-walled cysts. Conclusion. H&E staining of corneal cytology specimens is an efficient and readily available test for diagnosis of Acanthamoeba keratitis. PMID- 27403363 TI - Pediatric Myofibroma of the Palate with Ulceration and Bone Destruction. AB - Myofibroma is a rare benign neoplasm occurring in the head and neck, arising primarily in infants and children. Frequently, myofibromas grow rapidly leading to suspicion of malignancy and the potential for overaggressive surgical excision. We aim to report a rare case of myofibroma with ulceration and bone destruction. A nine-year-old female presented with an ulcerated left hard palate mass. Open biopsy was performed with pathology suggestive of myofibroma. A left partial maxillectomy and reconstruction with a buccal advancement flap were performed. Final pathology confirmed the diagnosis of a benign myofibroma. Myofibroma is a rare benign tumor of the head and neck which must be considered in the differential diagnosis by the clinician and the pathologist in order to prevent inappropriate and/or overaggressive treatment. PMID- 27403364 TI - A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings. AB - Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs) which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22)(p13;q12) translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22)(p13;q12) translocation disclosed loss of the EWSR1 gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based comparative genomic hybridization (a-CGH) confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of the EWSR1 and WT1 gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs. PMID- 27403365 TI - Ibuprofen for Ductus Arteriosus Months after Birth. AB - Ibuprofen is a well-known agent used to treat patent ductus arteriosus in preterm neonates in the first days of life. In the current case report we illustrate the potential use of ibuprofen in two preterm neonates 60 and 88 days after birth, respectively. To our knowledge, this is the first report on the effects of ibuprofen on patent ductus arteriosus in preterm newborns after months of life. These cases suggest that the ductus arteriosus does not become refractory for ibuprofen after the first days of life. Late closure of the duct with ibuprofen might still improve the cardiorespiratory condition and prevent infants from surgical closure. Controlled trials are necessary to further study these findings. PMID- 27403366 TI - Valproate Induced Hypertensive Urgency. AB - Valproate is a medication used in the treatment of seizures, bipolar disorder, migraines, and behavioral problems. Here we present a case of an 8-year-old boy who presented with hypertensive urgency after initiation of valproate. Primary treatment of his hypertension was ineffective. Blood pressure stabilization was achieved following discontinuation of valproate. Clinicians should be aware of the risk of developing hypertensive urgency with administration of valproate. PMID- 27403367 TI - Bilateral Morgagni Hernia: A Unique Presentation of a Rare Pathology. AB - Morgagni hernia is an unusual congenital herniation of abdominal content through the triangular parasternal gaps of the anterior diaphragm. They are commonly asymptomatic and right-sided. We present a case of a bilateral Morgagni hernia resulting in delayed growth in a 10-month-old boy. The presentation was unique due to its bilateral nature and its symptomatic compression of the mediastinum. Diagnosis was made by 3D reconstructed CT angiogram. The patient underwent medical optimization until he was safely able to tolerate laparoscopic surgical repair of his hernia. Upon laparoscopy, the CT findings were confirmed and the hernia was repaired. PMID- 27403368 TI - A Novel Technique for Managing Pancreaticojejunal Anastomotic Leak after Pancreaticoduodenectomy. AB - Pancreaticoduodenectomy (Whipple's procedure) remains the only definitive treatment option for tumors of the periampullary region. The most common and life threatening complications following the procedure are pancreatic anastomotic leakage and subsequent fistula formation. When these complications occur, treatment strategy depends on the severity of anastomotic leakage, with patients with severe leakages requiring reoperation. The optimal surgical method used for reoperation is selected from among different options such as wide drainage, definitive demolition of the pancreaticojejunal anastomosis and performing a new one, or completion pancreatectomy. Here we present a novel, simple technique to manage severe pancreatic leakage via ligamentum teres hepatis patch. PMID- 27403369 TI - Management of Ureterolithiasis in a Patient with Crossed Unfused Renal Ectopia. AB - Crossed renal ectopia is a rare congenital anomaly in which both kidneys are situated on one side and fused together in 85%-90% of cases. The management of urinary calculi in patients with crossed renal ectopia continues to pose challenges to urologists because the aberrant anatomy may make access and clearance of the calculi more difficult to accomplish. Here, we report a case of inferior crossed renal ectopia, without fusion, and a ureteral stone in which the patient was treated successfully by extracorporeal shock wave lithotripsy. PMID- 27403370 TI - Predictors of Regional Lymph Node Recurrence after Initial Thyroidectomy in Patients with Thyroid Cancer. AB - Background. Regional lymph node recurrence (RLNR) is common in patients with thyroid cancer but clinicopathological predictors are unclear. We aimed to clarify these predictors and identify patients who would benefit from prophylactic lymph node dissection the most. Method. 343 patients with different types of thyroid cancer were analyzed retrospectively. All patients underwent total thyroidectomy between 2007 and 2013. Results. The median +/- interquartile range of patients' age was 40 +/- 25 years. 245 (71.4%) patients were female. Regarding the risk of regional lymph node recurrence, we found that male gender, age >=45 years, non-PTC (i.e., medullary, follicular, and anaplastic types) histopathology, T3 (i.e., tumor size >4 cm in the greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension), stage IVa, and isolated cervical lymphadenopathy as initial manifestation (ICL) are significant risk factors. T3 (p < 0.001; odds ratio = 156.41, 95% CI [55.72-439.1]) and ICL (p < 0.001; odds ratio = 77.79, 95% CI [31.55-191.81]) were the strongest predictors of regional lymph node recurrence. Conclusion. We found easily achievable risk factors for RLNR in thyroid cancers patients. We suggested that patients with specific clinicopathological features like male gender, age >=45 years, larger tumor size, and extrathyroidal extension be considered as prophylactic lymphadenectomy candidates. PMID- 27403371 TI - The Effect of Long Lasting Insecticide Bed Net Use on Malaria Prevalence in the Tombel Health District, South West Region-Cameroon. AB - Malaria remains a major public health problem in Africa, and its prevalence in Cameroon stands at 29%. Long Lasting Insecticide Nets (LLINs) were distributed in 2011 to reduce malaria mortality and morbidity; however, assessment of this intervention is scanty. The present study in the Tombel health district (THD) investigated the impact of this distribution on malaria prevalence. A total of 31,657 hospital records from 3 health facilities in 3 health areas for 2010-2013 were examined. Records for 2010 and 2011 provided predistribution baseline data, while those of 2012 and 2013 represented postdistribution data. 8,679 (27.4%) patients were positive for malaria. Children below 5 years had the highest prevalence (40.7%). The number of confirmed cases was highest from June to August (peak rainy season). Malaria prevalence was higher in males (25.3%) than in females (23.2%). Malaria prevalence increased in THD from 26.7% in 2010 to 30.7% in 2011 but dropped to 22.7% in 2012 and then increased in 2013 to 29.5%. There was an overall drop in the total number of confirmed malaria cases in 2012; this decrease was significant in Ebonji (p < 0.001) and Nyasoso (p < 0.015) health areas. The distribution of LLINs led to a short lived reduction in malaria prevalence in THD. LLIN distribution and other control activities should be reinforced to keep malaria prevalence low especially among the 0-5-year group. PMID- 27403372 TI - Evaluation of Nonmotor Symptoms in Diagnosis of Parkinsonism and Tremor. AB - Background. Nonmotor symptoms particularly olfactory dysfunction, RBD, depression, hallucinations, and constipation are currently not included in the typical clinical criteria for diagnosing Lewy body Parkinsonian disorders (LBPD). The aim of this study is to determine the diagnostic value of nonmotor symptoms in patients presenting with Parkinsonism and tremor. Methods. All new patients seen between January 2007 and May 2013 in the Movement Disorders Specialist Clinics of the Royal Melbourne Hospital (RMH), who were referred with a possible neurodegenerative syndrome or concerns of Parkinsonism and/or tremor, were included. Patients underwent routine evaluation with the four-minute "Sniffin Sticks" test, RBD, depression, and constipation. Results. 291 patients were included in the analysis. Conclusion. We found that lower olfaction scores based on "Sniffin Sticks" testing combined with reports of depression and constipation are independent predictors for the diagnosis of the spectrum of Lewy body Parkinsonian disorders (LBPD). Parkinson's disease (PD) cannot be reliably clinically differentiated from other causes of Parkinsonism that share symptomatology and structural abnormalities. PMID- 27403373 TI - Nutritional Status and Anthropometric Indices in High School Girls in Ilam, West Iran. AB - Background. Adolescence is one of the most challenging periods for human growth and nutritional status. The aim of this study was to assess the nutritional status and anthropometric indices in high school girls in Ilam. Methods. This cross-sectional study was performed on 360 domestic high school girl students chosen randomly by cluster sampling. Data were gathered through interviews performed by a dietitian to fill 24-hour dietary recall and food frequency and demographic questionnaires. Then we performed the anthropometric measurements and we compared the results with CDC2000 standards. We analyzed our data by N4 food analyzer and SPSS16 software. Results. The prevalence of obesity and overweight was 5% and 10.8%, respectively. Simultaneously, the prevalence of underweight was 20.2%. The prevalence of stunting was 5.8%. We also showed that 50% of high school girls in Ilam suffered from severe food insecurity, 14.7% suffered from mild insecurity, and 4.7% get extra energy from foods. Food analysis showed that micronutrients such as zinc, iron, calcium, folate, fiber, magnesium, and vitamin B12 were less than what is recommended by the RDA. Conclusion. Undernutrition and overnutrition are completely prevalent among girls studied in Ilam. This needs further acts and investigations in the field and more nutritional and health educations. PMID- 27403374 TI - Using an Interactive Systems Framework to Expand Telepsychology Innovations in Underserved Communities. AB - Literature indicates that the use of promising innovations in mental health care can be improved. The advancement of telepsychology is one innovation that has been utilized as a method to reduce rural health disparities and increase the number of people with access to mental health services. This paper describes a successful pilot telepsychology program implemented in a rural community to increase access to mental health services and the model's replication and expansion into four additional communities using concepts described in an Interactive Systems Framework. The Interactive Systems Framework highlights how building local capacity specific to organizational functioning and innovations are necessary to support, deliver, and disseminate innovations within new settings. Based on the knowledge gained from this telepsychology innovation, the application of an Interactive Systems Framework and funding mechanisms are discussed. PMID- 27403375 TI - A Pathological Analysis of Canaliculitis Concretions: More Than Just Actinomyces. AB - Purpose. Canaliculitis is classically associated with Actinomyces species, which are filamentous bacteria; the purpose of this study was to evaluate the extent to which nonfilamentous bacteria colonize canalicular concretions by using graded histopathological analysis. Methods. This is a series of 16 cases. The percentage of Gram-positive/Gomori's methenamine silver-positive filamentous bacteria (Actinomyces) versus the total bacteria identified was graded, and the types of bacteria seen were recorded. Nonfilamentous bacteria were categorized based upon Gram stain (positive or negative) and morphology (cocci or rods). Results. There were 11 females and 5 males. Nonfilamentous bacteria were identified in 16 of 16 (100%) specimens and filamentous bacteria were identified in 15 of 16 (94%) specimens. The mean percentage of filamentous bacteria relative to total bacteria was 57%. Regarding the nonfilamentous bacteria present, 69% of specimens had Gram positive cocci only, 25% had Gram-positive and Gram-negative cocci, and 6% had Gram-positive cocci and Gram-positive rods. Conclusion. In the current study, there was a mix of filamentous and nonfilamentous bacteria in almost all canalicular concretions analyzed. Nonfilamentous bacteria may contribute to the pathogenesis of canaliculitis. In addition, the success of bacterial culture can be variable; therefore, pathological analysis can assist in determining the etiology. PMID- 27403376 TI - Skin Biophysical Characteristics in Patients with Keratoconus: A Controlled Study. AB - Background. Keratoconus is a relatively common corneal disease causing significant visual disability. Individuals with connective tissue disorders that affect the skin such as Marfan's syndrome and Ehlers-Danlos syndrome or patients with atopic dermatitis show an increased prevalence of keratoconus. It seems that there are some concurrent alterations of skin and cornea in patients with keratoconus. Objective. We plan to compare skin biophysical characteristics in patients with keratoconus and healthy controls. Methods. Forty patients with keratoconus (18 females and 22 males) with mean (SD) age of 33.32 (9.55) years (range 19-56) and 40 healthy controls were recruited to this study. Skin biophysical characteristics including cutaneous resonance running time (CRRT), stratum corneum hydration, and melanin values were measured in patients and controls. Results. The median CRRT, stratum corneum hydration, and melanin measurements were significantly lower in patients with keratoconus in comparison with healthy controls. Conclusion. There are some alterations of skin biophysical properties in patients with keratoconus. Therefore, the assessment of these skin parameters could provide us some clues to the possible common biophysical variations of cornea and skin tissue in diseases such as keratoconus. PMID- 27403377 TI - Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation. AB - The Transdermal Drug Delivery System (TDDS) is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP) is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra), Zanjabeel (Zingiber officinale), Podina (Mentha arvensis), and Sirka (Vinegar) were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 +/- 1 degrees C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics. PMID- 27403378 TI - Biomimetic Synthesis of Silver Nanoparticles Using Endosymbiotic Bacterium Inhabiting Euphorbia hirta L. and Their Bactericidal Potential. AB - The present investigation aims to evaluate biomimetic synthesis of silver nanoparticles using endophytic bacterium EH 419 inhabiting Euphorbia hirta L. The synthesized nanoparticles were initially confirmed with change in color from the reaction mixture to brown indicating the synthesis of nanoparticles. Further confirmation was achieved with the characteristic absorption peak at 440 nm using UV-Visible spectroscopy. The synthesized silver nanoparticles were subjected to biophysical characterization using hyphenated techniques. The possible role of biomolecules in mediating the synthesis was depicted with FTIR analysis. Further crystalline nature of synthesized nanoparticles was confirmed using X-ray diffraction (XRD) with prominent diffraction peaks at 2theta which can be indexed to the (111), (200), (220), and (311) reflections of face centered cubic structure (fcc) of metallic silver. Transmission electron microscopy (TEM) revealed morphological characteristics of synthesized silver nanoparticles to be polydisperse in nature with size ranging from 10 to 60 nm and different morphological characteristics such as spherical, oval, hexagonal, and cubic shapes. Further silver nanoparticles exhibited bactericidal activity against panel of significant pathogenic bacteria among which Pseudomonas aeruginosa was most sensitive compared to other pathogens. To the best of our knowledge, present study forms first report of bacterial endophyte inhabiting Euphorbia hirta L. in mediating synthesizing silver nanoparticles. PMID- 27403379 TI - The Role of p16, p21, p27, p53 and Ki-67 Expression in the Differential Diagnosis of Cutaneous Squamous Cell Carcinomas and Keratoacanthomas: An Immunohistochemical Study. AB - BACKGROUND: Distinguishing squamous cell carcinoma (SCC) from keratoacanthoma (KA) by histopathological features may not be sufficient for a differential diagnosis, as KAs may, in some cases, imitate well-differentiated SCCs. AIMS: In this study, we investigated whether the expression of the p16, p21, p27, p53 genes and a Ki-67 proliferation index are useful in distinguishing between these two tumors. STUDY DESIGN: Cross-sectional study. METHODS: Immunohistochemistry was used to investigate the expression of the p16, p21, p27, p53 genes and the Ki 67 proliferation index was investigated in well-differentiated SCC with KA-like features (n=40) and KA (n=30). RESULTS: The results of all of the examined markers, except for p27 (p16, p21, p53, and Ki-67) were found to be significantly different between the SCC and KA samples (p<0.05). CONCLUSION: In well differentiated SCC with KA-like features and KA cases where the differential diagnosis is difficult from a histopathological perspective, the use of p16, p21, p53 expression and a Ki-67 proliferation index can be useful for the differential diagnosis of SCCs and KAs. PMID- 27403380 TI - eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease. AB - BACKGROUND: Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. AIMS: The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. STUDY DESIGN: Case-control study. METHODS: In this study, genotype distributions of Glu-298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. CONCLUSION: Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients. PMID- 27403381 TI - Resveratrol Prevented Lipopolysaccharide-Induced Endothelial Dysfunction in Rat Thoracic Aorta Through Increased eNOS Expression. AB - BACKGROUND: The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. AIMS: The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. STUDY DESIGN: Animal experiment. METHODS: Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later. RVT was injected intraperitoneally 15 minutes before LPS administration. Six hours after LPS injection, potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) were used to examine to vascular reactivity and endothelial function. eNOS, phospho-eNOS (p-eNOS) (Ser 1177), and SIRT1 expressions in thoracic aorta were evaluated by Western blot. RESULTS: LPS administration significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. Phe- and KCl-induced contractile responses in the thoracic aorta significantly decreased in LPS-injected group. eNOS and p-eNOS expression decreased significantly in arteries obtained from LPS group rats. The impaired vasoreactivity as well as decreased expressions of eNOS, p-eNOS, and SIRT1 in vessels from LPS-injected rats were improved by RVT treatment. CONCLUSION: The endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by LPS administration, and RVT treatment may improve vascular endothelial function. The protective effect of RVT might be associated with increased eNOS expression and activity. PMID- 27403382 TI - Evaluation of Cisplatin Neurotoxicity in Cultured Rat Dorsal Root Ganglia via Cytosolic Calcium Accumulation. AB - BACKGROUND: Calcium homeostasis is considered to be important in antineoplastic as well as in neurotoxic adverse effects of cisplatin. AIMS: This study aimed to investigate the role of Ca(2+) in cisplatin neurotoxicity in cultured rat dorsal root ganglia (DRG) cells. STUDY DESIGN: Cell culture study. METHODS: DRG cells prepared from 1-day old Sprague-Dawley rats were used to determine the role of Ca(2+) in the cisplatin (10-600 MUM) neurotoxicity. The cells were incubated with cisplatin plus nimodipine (1-3 MUM), dizocilpine (MK-801) (1-3 MUM) or thapsigargin (100-300 nM). Toxicity of cisplatinon DRG cells was determined by the MTT assay. RESULTS: The neurotoxicity of cisplatin was significant when used in high concentrations (100-600 MUM). Nimodipine (1 MUM) but not MK-801 or thapsigargin prevented the neurotoxic effects of 200 MUM of cisplatin. CONCLUSION: Voltage-dependent calcium channels may play a role in cisplatin neurotoxicity. PMID- 27403383 TI - Perceived Social Support and Its Impact on Mental Fatigue in Patients with Mild Traumatic Brain Injury. AB - BACKGROUND: Although mental fatigue was well-recognized as one of the long-term consequences following mild traumatic brain injury (MTBI) that required ongoing support, evidences for the optimal management remained inadequate. AIMS: To investigate the temporal profile of mental fatigue during the first year after MTBI and examine the impact of perceived social support on the recovery from post MTBI fatigue. STUDY DESIGN: Observational case-control study. METHODS: This study was conducted among post-MTBI patients admitted to the emergency department in a tertiary-care hospital in Sichuan, China. During four waves of assessments at 1 week, 3, 6 and 12 months, mental fatigue was assessed through Mental Fatigue Scale (MFS) whereas social support was assessed by the Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: There were 65.1%, 37.1%, 34.8% and 32.5% individuals being identified as those with mental fatigue at 1 week, 3, 6 and 12 months, respectively. The scores of MFS didn't change substantially since 3 months post-injury. Compared to non-fatigued MTBI patients, those with long lasting post- MTBI fatigue reported extremely lower level of perceived social support. Moreover, improved social support at 1 week was negatively associated with the occurrence of long-lasting fatigue. CONCLUSION: Sufficient social support could significantly decrease the occurrence of long-lasting mental fatigue among MTBI cases. It seemed of great importance to modify the emphasis of rehabilitation to include assessment and improvement of perceived social support at earlier stages after injury. PMID- 27403384 TI - Investigating the Impacts of Preoperative Steroid Treatment on Tumor Necrosis Factor-Alpha and Duration of Extubation Time underwent Ventricular Septal Defect Surgery. AB - BACKGROUND: Cardiopulmonary bypass is known to cause inflammatory events. Inflammation occurs due to many known important biological processes. Numerous mechanisms are known to be responsible for the development of inflammatory processes. Currently, there are many defined mediators as a tumor necrosis factor alpha (TNF-alpha) playing an active role in this process. AIMS: This research was to investigate the effects of pre-operative steroid use on inflammatory mediator TNF-alpha and on time to extubation postoperatively in ventricular septal defect patients undergoing cardiopulmonary bypass surgery. STUDY DESIGN: Controlled clinical study. METHODS: This study included 30 patients. These patients were assigned into two groups, each containing 15 patients. 5 micrograms/kg methylprednisolone was injected intravenously 2 hours before the surgery to Group I, whereas there was no application to the patients in Group II. TNF-alpha (pg/mL) level was measured in arterial blood samples obtained at four periods including: the preoperative period (Pre TNF); at the 5(th) minute of cross clamping (Per TNF); 2 hours after termination of cardiopulmonary bypass (Post TNF); and at the postoperative 24th hours in cardiovascular surgery intensive care unit (Post 24 h TNF). RESULTS: The mean cross-clamp time was 66+/-40 and 55+/-27 minutes in Group I and Group II respectively. No significant difference was found between the groups in terms of cross-clamp time (p>0.05). The mean time to extubation was 6.1+/-2.3 hours in Group I and 10.6+/-3.4 hours in Group II. Group I extubation time was significantly shorter than Group II. Group I TNF alpha levels at Post TNF and Post24h TNF was lower than Group II. These differences are also statistically significant (p<0.05). CONCLUSION: There is a strong indication that preoperative steroid treatment reduced the TNF-alpha level together with shortens duration of postoperative intubation and positively contributes to extubation in ventricular septal defect patients operated in cardiac surgery with cardiopulmonary bypass. (ClinicalTrials.gov Identifier: TCTR20150930001). PMID- 27403385 TI - Oral Health, Obesity Status and Nutritional Habits in Turkish Children and Adolescents: An Epidemiological Study. AB - BACKGROUND: Studies evaluating the relationship between oral health status and obesity have provided conflicting data. Therefore, there is a great need to investigate and clarify the possible connection in a comprehensive sample. AIMS: To assess the relationship of obesity and oral health status among children and adolescents aged 6 to 17 years-old. STUDY DESIGN: Cross-sectional study. METHODS: Data were obtained from 4,534 children and adolescents (2,018 boys and 2,516 girls). Questionnaires were sent home prior to examination; afterwards, anthropometric and dental data were collected from participants. Community Periodontal Index (CPI) and number of decayed, missing, and filled teeth in the permanent dentition (DMFT), and deciduous dentition (dmft) index were used to measure oral health status. Height, body weight, body mass index (BMI), waist circumference (WC), and body fat percentage were analyzed. RESULTS: For DMFT scores, healthy (score=0) girls and boys had significantly higher BMI and WC values than unhealthy (score>1) girls and boys (p<0.05). Healthy girls had higher fat percentage values than unhealthy girls (p<0.05). In terms of CPI scores, healthy boys had lower BMI and WC values than unhealthy boys (p<0.05). According to multiple binary logistic regression results for model 1, BMI predicted DMFT scores in both genders but CPI scores only in boys. No beverage consumption predicted DMFT scores in boys, while milk consumption predicted DMFT scores in girls. No meal skipping predicted CPI scores in boys. For model 2, WC predicted DMFT scores in both genders and CPI scores only in boys. Milk consumption predicted DMFT scores only in girls. No meal skipping predicted CPI scores for both gender (p<0.05). According to DMFT, there were significant differences between the frequencies of the BMI groups (normal weight, overweight and obese) at the age of 7 (girls only), 9, 10, and 16 (boys only) years and overall (only girls) (p<0.05). According to CPI, significant differences between the frequencies of the BMI groups at the age of 16 (boys only) and 17 (girls only) were seen (p<0.05). CONCLUSION: Periodontal and dental status appears to correlate with nutritional habits and obesity. Obesity and dental/periodontal diseases are multifactorial diseases that follow similar risk patterns and develop from an interaction between chronic conditions originating early in life. It is important for all health professionals to educate patients at risk about the progression of periodontal and dental diseases and the importance of proper oral hygiene. PMID- 27403386 TI - Marmara University Medical Students' Perception on Sexual Violence against Women and Induced Abortion in Turkey. AB - BACKGROUND: Historically, sexual assault is a common issue in Turkey. As doctors are one of the steps to help sexually assaulted women, medical students should have basic knowledge of and sensitivity regarding this subject. Another common women's public health issue is induced abortion. In countries where access to abortion is restricted, there is a tendency towards unhealthy abortion. AIMS: The aims of this study are: (1) to determine the attitudes and opinions of Marmara University Medical Faculty students about sexual assault against women and induced abortion and (2) to propose an educational program for medical students about sexual assault and abortion. STUDY DESIGN: Cross-sectional study. METHODS: The questionnaires were self-administered and the data were analyzed using SPSS v.15.0. First, the descriptive statistics were analyzed, followed by Chi-square for contingency tests assessing differences in attitudes toward sexual assault and induced abortion by factors such as gender and educational term. Differences were considered statistically significant at p<0.05. RESULTS: About 89.6% of the participants (n=266) reported that they had never been sexually assaulted and about 11.5% of the women (n=19) had been sexually assaulted. There was no significant relationship between previous sexual assault and gender (p>0.05). Although there was no significant difference regarding the extent of punishment by victim's status as a virgin, 21.3% (n=63) agreed that punishment should be more severe when the victim was a virgin. About 40.7% (n=120) agreed that the legal period of abortion in Turkey (10 weeks) should be longer. The majority (86.1%, n=255) agreed that legally prohibiting abortions causes an increase in unhealthy abortions. CONCLUSION: An educational program on these issues should be developed for medical students. PMID- 27403387 TI - A Comparision of the Effect of Sugammadex on the Recovery Period and Postoperative Residual Block in Young Elderly and Middle-Aged Elderly Patients. AB - BACKGROUND: The importance of the characteristics of anesthesia and postoperative residual curarization (PORC) in the elderly population should be a growing concern in this century. AIMS: To investigate the effect of sugammadex on the duration of the recovery from neuromuscular blocking agents and postoperative residual curarization in the young elderly and middle-aged elderly patients who underwent elective laparoscopic cholecystectomy, followed by a train of four (TOF) watch monitorization. STUDY DESIGN: Prospective clinical trial study. METHODS: Sixty patients over the age of 65 with American Society of Anesthesiologists I-III were divided into two groups according to their age (65 74 years old and >=75 years old). Patients received sugammadex (2.0 mg/kg iv) at the reappearance of the second twitch of the TOF as an agent for reversal of neuromuscular blockage at the end of surgery. Patients were extubated at the time of TOF >=0.9. The patients' TOF responses were evaluated with regards to PORC in at the 5th minute and were followed up for one hour in the recovery room. Reintubation was applied for those patients who developed PORC and had peripheric oxygen saturation <90% despite being given 6 L oxygen per min with a face mask. RESULTS: The onset time of neuromuscular blocking agent and time from T2 to achieve TOF ratio 90% (the duration of sugammadex effect) or over were found to be longer in the middle-aged elderly group than in the young elderly group. A statistically significant relationship was found between age and the duration of TOF ratio to reach 0.9 in the same direction. The PORC incidence and rate of reintubation were found to be 1.7% in all patients. CONCLUSION: In our opinion, it is necessary to remember that the duration of sugammadex effect on the recovery period is prolonged for patients who are aged >=75 years compared to patients aged between 65-74 years. (ClinicalTrials.gov Identifier: ACTRN12615000758505). PMID- 27403388 TI - Oxidative Stress Biomarkers and Adenosine Deaminase over the Alopecic Area of the Patients with Alopecia Areata. AB - BACKGROUND: Alopecia areata (AA) is an autoimmune, T-cell mediated, and chronic inflammatory disorder. The pathological mechanisms of disease are unclear, but oxidative stress may be involved. To our knowledge, no studies have examined the oxidative stress levels or biomarkers within the lesional area and skin surface in patients with AA. Similarly, adenosine deaminase (ADA) has not been characterized in AA. AIMS: Therefore, we aimed to define ADA levels and the factors involved in oxidative stress from scalp-scrapes of patients with AA. STUDY DESIGN: Case-control study. METHOD: A total of 60 patients (30 diagnosed AA patients and 30 healthy controls) were included in the study. ADA as well as oxidative stress factors, including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analyzed from scalp scrapes in both groups and quantified by spectrophotometry. RESULTS: Activities of SOD (p=0.000), CAT (p=0.033), and ADA (p=0.004) as well as levels of GSH (p=0.000) and MDA (p=0.032) in patients with AA were higher than the controls statistically significant. CONCLUSION: Based on these results, factors associated with oxidative stress were elevated in AA patient scalp-scrapes compared to controls and may have a defined role the disease pathogenesis. Alterations in the activities of antioxidant enzymes from AA patient scraping samples may be a local effect of elevated oxidative stress levels. In this disease, oxidative stress may affect not only hair follicle but also any layers of the skin. PMID- 27403389 TI - Comparing the Efficacy of 7%, 3% and 0.9% Saline in Moderate to Severe Bronchiolitis in Infants. AB - BACKGROUND: There is no standard treatment option in acute bronchiolitis. 3-7% hypertonic saline (HS) seems to be the effective treatment choice for reducing the hospitalization day. AIMS: To compare the effect of nebulized 7% HS/salbutamol and 3% HS/salbutamol to 0.9% saline/salbutamol. The primary outcome measure was the effect of study drugs on the length of hospital stay (LOS). Secondary outcome measures were safety and efficacy in reducing the clinical severity score (CSS) at the 24 hours of the study. STUDY DESIGN: Prospective, double-blinded randomized clinical study. METHODS: The study consists of 104 infants. Groups were constituted according to the treatment they received: These are, group A - 0.9% saline/salbutamol, group B -3% HS/salbutamol and group C-7% HS/salbutamol. Heart beat, Bronchiolitis CSS and oxygen saturation of the patients were determined before and after nebulization. The patients were monitored for adverse reactions. RESULTS: Length of hospital stay in group A, B and C were as follows; 72.0 (20-288) hours in group A, 64.0 (12-168) hours in group B and 60.0 (12-264) hours in group C. No significant differences was observed among three groups (p>0.05). CONCLUSION: 7% HS and 3% HS does not have any effect to decrease LOS for infants with bronchiolitis. PMID- 27403390 TI - Short-Term Outcomes and Mortality of Late Preterm Infants. AB - BACKGROUND: Late preterm infants have increased rates of morbidity and mortality compared to term infants. Determining the risk factors in these infants leads to more comprehensive preventive and treatment strategies. AIMS: Our aim was to analyse the morbidity rates such as respiratory system diseases, infections, congenital anomalies, hypoglycemia and hematologic abnormalities and mortality rates in a large group of patients at a referral center. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Medical records of late preterm and term infants who were managed at the referral center were analysed. RESULTS: 41752 births were analysed in 3 years. 71.9% of all births were between 37-42 gestational weeks (i.e. term) and 16.1% were between 34-37 weeks (i.e. late preterm). Compared to term infants, late preterm infants had increased rates of short-term problems. The rate of mortality increased with decreased gestational age. The duration of hospitalization was significantly higher in the smallest late preterm infants. CONCLUSION: This study demonstrated the need that late preterm infants who have higher risk for morbidity and mortality, compared to term infants require close monitoring. The rate of mortality and hospitalization increased with decreased gestational age. PMID- 27403391 TI - The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats. AB - BACKGROUND: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. AIMS: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. STUDY DESIGN: Animal experiment. METHODS: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. RESULTS: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42(nd) day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p<0.05). Under microscopic evaluation, we observed the greatest amount of nerve regeneration in group 1 and the lowest in group 3. However, this difference was not statistically significant. Moreover, there was no significant difference in the bone mineral density (BMD) levels among the groups. CONCLUSION: We believe that a daily single dose of sildenafil plays an important role in the treatment of sciatic nerve damage and bone healing and thus can be used as supportive clinical treatment. PMID- 27403392 TI - Nasal Bacterial Colonization in Pediatric Epistaxis: The Role of Topical Antibacterial Treatment. AB - BACKGROUND: Epistaxis is a common problem in childhood. It has been shown that children with recurrent epistaxis are more likely to have nasal colonization with Staphylococcus aureus. It has been suggested that low-grade inflammation, crusting and increased vascularity due to bacterial colonization contributes to the development of epistaxis in children. AIMS: This study aimed to investigate the nasal colonization and treatment outcome in pediatric epistaxis patients. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Charts of the pediatric patients referred to our university hospital otolaryngology outpatient clinics for the evaluation of epistaxis were reviewed. The patients whose nasal cultures had been taken at the first clinical visit comprised the study group. RESULTS: Staphylococcus aureus was the most common bacteria grown. The presence of crusting and hypervascularity was not dependent on the type of bacterial growth and there was no relation between hypervascularity and crusting of the nasal mucosa. Thirty-six patients were evaluated for the outcome analysis. Resolution of bleeding was not dependent on nasal colonization; in patients with colonization, there was no difference between topical antibacterial and non antibacterial treatments. CONCLUSION: Despite the high colonization rates, topical antibacterial treatment was not found superior to non-antibacterial treatment. Our study does not support the belief that bacterial colonization results in hypervascularity of the septal mucosa causing epistaxis since no relation was found between nasal colonization, hypervascularity and crusting. The role of bacterial colonization in pediatric epistaxis need to be further investigated and treatment protocols must be determined accordingly. PMID- 27403393 TI - Autologous Blood Injection Works for Recalcitrant Lateral Epicondylitis. AB - BACKGROUND: Recalcitrant lateral epicondylitis may be a disabling condition. Treatment of this condition is still controversial. AIMS: In the present prospective study, we evaluated the long-term results of autologous blood injection for the treatment of recalcitrant lateral epicondylitis. STUDY DESIGN: Prospective clinical study. METHODS: A total of 42 elbows of 40 consecutive patients (28 female, 12 male) were enrolled in this prospective study. Seven patients left the study (3 patients moved to another city, 1 patient died in the second week due to a heart condition, 1 patient quit the study because of the resolution of pain in the fourth week and 2 patients did not agree to the second injection). Thirteen patients were lost to third year follow-up. Therefore, a total of 21 elbows of 20 patients with 3 years of follow-up were included in this study. The mean age of the patients was 47.25 years (range, 20-68 years). RESULTS: Visual analogue scale (VAS), Nirschl score and grip strength were significantly improved after injections when compared to before treatment. The best improvement in terms of grip strength, Nirschl score and VAS score was detected at the one year follow-up. The improvement in Nirschl and VAS score sustained until the third year. CONCLUSION: We suggest that autologous blood injection for the treatment of recalcitrant lateral epicondylitis is an effective, safe and successful procedure in the long-term. PMID- 27403394 TI - Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion. AB - BACKGROUND: Stroke is one of the most common causes of death and the leading cause of disability in adults. Cerebral ischemia/reperfusion injury causes cerebral edema, hemorrhage, and neuronal death. AIMS: In post-ischemic reperfusion, free radical production causes brain tissue damage by oxidative stress. Pregabalin, an antiepileptic agent was shown to have antioxidant effects. The aim of this study was to evaluate the neuroprotective and antioxidant effects of pregabalin on ischemia and reperfusion in rat brain injury. STUDY DESIGN: Animal experimentation. METHODS: Male Wistar rats weighing (250-300 g) were randomly divided into six groups, each consisting of 6 rats: control (C), pregabalin (P), ischemia (I), pregabalin + ischemia (PI), ischemia + reperfusion (IR) and ischemia + reperfusion + pregabalin (PIR). Rats were initially pre treated with 50 mg/kg/d pregabalin orally for two days. Then, animals that applied ischemia in I, PI, IR and PIR groups were exposed to carotid clamping for 30 minutes and 20 minutes reperfusion was performed in the relevant reperfusion groups. RESULTS: NR2B receptor levels were significantly lower in the PIR group in comparison to the IR group. In the PIR group, Thiobarbituric acid reactive substance (TBARS) level had statistically significant decrease compared with IR group. Glutathione peroxidase (GSH-PX) levels were also significantly increased in the PIR group compared with I, IR and control groups. In the PI and PIR groups, catalase (CAT) levels were also significantly increased compared with I and IR groups (p=0.03 and p=0.07, respectively). CONCLUSION: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future. PMID- 27403395 TI - Idiopathic Granulomatous Mastitis Associated with Erythema Nodosum. AB - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is an uncommon benign chronic inflammatory breast disease, and erythema nodosum (EN) is an extremely rare systemic manifestation of IGM. Here, we report a rare case of IGM accompanied by EN. CASE REPORT: A 32-year-old patient was admitted to our clinic with a history of a tender mass in the right breast. On physical examination, the right breast contained a hard, tender mass in the lower half with indrawing of the nipple. She had florid EN affecting both legs. She was evaluated with mammography, ultrasound, power Doppler ultrasound, non-enhancing magnetic resonance imaging (MRI), dynamic contrast-enhanced MRI, fine needle aspiration biopsy (FNAB) and excisional biopsy. Time-intensity curves showed a type II pattern on dynamic contrast-enhanced MRI, which has an intermediate probability for malignancy. The FNAB reported a benign cytology suggestive of a granulomatous inflammation, which was also supported by the histopathological findings. A partial mastectomy was performed following medical treatment. There was no recurrence at 1-year follow up. CONCLUSION: IGM should be considered in the differential diagnosis of EN. Although histopathological examination remains the only method for the definite diagnosis of IGM, MRI can be helpful in the diagnosis or differentiation of benign lesions from malignant ones. PMID- 27403396 TI - Benign Cystic Mesothelioma in a Child: Case Report and Review of the Literature. AB - BACKGROUND: Benign cystic mesothelioma (BCM) is a rare tumor with benign characteristic. There are only 8 child cases reported in the English literature. In this report, we present this rare entity a brief review of the literature. CASE REPORT: A two year-old boy presenting with abdominal swelling was hospitalized. Physical examination revealed a mass filling the abdomen. Laboratory findings were not specific. Abdominal computerized tomography showed a 15*13*11 cm cystic mass extending from the bladder to the liver with no solid components and no infiltration to adjacent organs. Operation revealed a cystic mass filled with yellow-green serous fluid which was attached to the right lobe of the liver with a 1 cm thick peduncle. Total excision of the mass was performed by clamping and cutting the narrow attachment. Recovery was uneventful. Pathology revealed multiple cysts lined with mesothelial cells. No recurrence was seen after 5 years of follow-up. CONCLUSION: BCM should be kept in mind as a rare cause of the abdominal mass in children, as it may lead to confusion in preoperative diagnosis. Although rare, patients should be followed throughout life because of the risk of recurrence and malignant degeneration. PMID- 27403397 TI - Uterine Cervix Metastasis of Myxopapillary Ependymoma Originated from the Spinal Cord. AB - BACKGROUND: Myxopapillary ependymomas are well differentiated low-grade tumors which have been documented to local or distant metastasis. In the literature, this is a unique case of myxopapillary ependymoma with metastasis to the uterine cervix. Here, we present a rare case of extra neural metastasis of spinal ependymoma that developed over a long period. CASE REPORT: A 34-year-old woman was referred to our hospital for pelvic mass. A mass (110*100 mm) localized between the sacrococcygeal region and the uterus was detected by magnetic resonance imaging. In 2004, she had been operated upon for myxopapillary ependymoma seated in the sacrococcygeal region for the first time. She underwent tumor resection eight times due to the recurrence of spinal tumor in the same region in nine years. Under the diagnosis of uterine neoplasm, we carried out radical hysterectomy, omentectomy and pelvic lymphadenectomy as the surgical procedure. The pathological findings were reported as myxopapillary ependymoma. Immunohistochemically, the myxopapillary ependymal cells showed strong positivity for glial fibrillary acidic protein, whereas they were negative for low molecular weight cytokeratin. The Ki-67 labeling index was about 2-3%. The patient had an uneventful postoperative period. She has remained free of symptoms in the year since surgery. CONCLUSION: Extra-spinal myxopapillary ependymoma is very rare, but it must be considered in the differential diagnosis of pelvic mass lesions. PMID- 27403398 TI - Load Dependency of Left Ventricular Diastolic Dysfunction Parameters. PMID- 27403399 TI - Chondroid Syringoma of the Hypothenar Region. PMID- 27403400 TI - High Prevalence of Liver Fibrosis in Patients with Human Immunodeficiency Virus Monoinfection and Human Immunodeficiency Virus Hepatitis-B Co-infection as Assessed by Shear Wave Elastography: Study at a Teaching Hospital in Kenya. AB - OBJECTIVES: The aim of this study was to determine the prevalence of liver fibrosis in patients with human immunodeficiency virus (HIV) monoinfection versus those with HIV hepatitis-B virus (HBV) co-infection as assessed with shear wave elastography (SWE) in a tertiary sub-Saharan Africa hospital. MATERIALS AND METHODS: A total of 105 consecutive patients, 70 with HIV monoinfection and 35 with HIV-HBV co-infection, had liver elastography obtained using SWE to assess for the presence of liver fibrosis the cutoff of which was 5.6 kPa. Assessment of aspartate aminotransferase-to-platelet ratio index (APRI) score (a noninvasive serum biomarker of liver fibrosis) in these patients was also done. RESULTS: The prevalence of liver fibrosis was significantly higher (P < 0.0001) in patients with HIV-HBV co-infection, 25.7%, compared to those with HIV monoinfection, 7.1%. APRI score was greater in patients with HIV-HBV co-infection than those with HIV monoinfection. HIV co-infection with HBV accelerates progression to liver fibrosis. Association of a low cluster of differentiation 4 (CD-4) count with advanced fibrosis supports earlier starting of antiretroviral therapy to prevent rapid progression of liver disease in HIV-positive patients. CONCLUSION: In view of the high prevalence of liver fibrosis in patients with HIV-HBV co-infection, regular monitoring of the disease progression is recommended. PMID- 27403401 TI - Sinonasal Fungal Infections and Complications: A Pictorial Review. AB - Fungal infections of the nose and paranasal sinuses can be categorized into invasive and non-invasive forms. The clinical presentation and course of the disease is primarily determined by the immune status of the host and can range from harmless or subtle presentations to life threatening complications. Invasive fungal infections are categorized into acute, chronic or chronic granulomatous entities. Immunocompromised patients with poorly controlled diabetes mellitus, HIV and patients receiving chemotherapy or chronic oral corticosteroids are mostly affected. Mycetoma and Allergic Fungal Rhinosinusitis are considered non invasive forms. Computer tomography is the gold-standard in sinonasal imaging and is complimented by Magnetic resonance imaging (MRI) as it is superior in the evaluation of intraorbital and intracranial extensions. The knowledge and identification of the characteristic imaging patterns in invasive - and non- invasive fungal rhinosinusitis is crucial and the radiologist plays an important role in refining the diagnosis to prevent a possible fatal outcome. PMID- 27403402 TI - Fungal Infections of the Central Nervous System: A Pictorial Review. AB - Fungal infections of the central nervous system (CNS) pose a threat to especially immunocompromised patients and their development is primarily determined by the immune status of the host. With an increasing number of organ transplants, chemotherapy, and human immunodeficiency virus infections, the number of immunocompromised patients as susceptible hosts is growing and fungal infections of the CNS are more frequently encountered. They may result in meningitis, cerebritis, abscess formation, cryptococcoma, and meningeal vasculitis with rapid disease progression and often overlapping symptoms. Although radiological characteristics are often nonspecific, unique imaging patterns can be identified through computer tomography as a first imaging modality and further refined by magnetic resonance imaging. A rapid diagnosis and the institution of the appropriate therapy are crucial in helping prevent an often fatal outcome. PMID- 27403403 TI - Thoracic Presentations of Small Round Blue Cell Tumors. AB - The term "small round blue cell" is frequently used as a cursory radiologic pathological correlation of aggressive tumors throughout the body. We present a pictorial essay of common and uncommon subtypes of small round blue cell tumors in the chest illustrating the characteristic radiologic findings of each lesion. In addition, we review the pathologic findings of each tumor subtype with characteristic hematoxylin- and eosin-stained photomicrographs and immunohistochemical and molecular studies. Represented tumors include small cell carcinoma, Ewing sarcoma, extranodal marginal zone B-cell lymphoma, embryonal rhabdomyosarcoma, desmoplastic small round cell tumor, and posttransplant lymphoproliferative disorder. Understanding and ability to recognize these lesions are essential to broaden the radiologist's differential diagnosis and help guide patient care. PMID- 27403404 TI - Viable Intrauterine Pregnancy and Coexisting Molar Pregnancy in a Bicornuate Uterus: A Rare Presentation. AB - A complete hydatidiform mole with a viable coexisting fetus (CMCF) is a rare occurrence. Similarly, Mullerian anomalies such as a bicornuate uterus are uncommon variants of normal anatomy. We report a case of a 40-year-old female with a known bicornuate uterus presenting at 13 weeks gestation with vaginal bleeding. Ultrasound findings showed a healthy viable pregnancy in the right horn with complete molar pregnancy in the left horn. After extensive counseling, the patient desired conservative management, however, was unable to continue due to profuse vaginal bleeding. The patient underwent suction dilation and curettage under general anesthesia and evacuation of the uterine horns. Postoperatively, the patient was followed until serum beta-human chorionic gonadotropin (beta-hCG) level dropped to <5 mU. This is the first case of a CMCF reported in a bicornuate uterus, diagnosed with the use of ultrasound imaging. PMID- 27403405 TI - Pathogenesis of Zika Virus-Associated Embryopathy. AB - A strong causal association has become evident between Zika virus (ZIKV) infection during pregnancy and the occurrence of fetal growth restriction, microcephaly and eye defects. Circumstantial evidence is presented in this paper in support of the hypothesis that these effects, as well as the Guillain-Barre syndrome, are due to an endogenous form of hypervitaminosis A resulting from ZIKV infection-induced damage to the liver and the spillage of stored vitamin A compounds ("retinoids") into the maternal and fetal circulation in toxic concentrations. Retinoids are mainly stored in the liver (about 80%) and are essential for numerous biological functions. In higher concentration, retinoids are potentially cytotoxic, pro-oxidant, mutagenic and teratogenic, especially if sudden shifts occur in their bodily distribution. Although liver involvement has not been mentioned specifically in recent reports, conventional liver enzyme tests underestimate the true extent of liver dysfunction. The proposed model could be tested by comparing retinoid concentration and expression profiles in microcephalic newborns of ZIKV-infected mothers and nonmicrocephalic newborn controls, and by correlating these profiles with measures of clinical severity. PMID- 27403406 TI - Intratympanic dexamethasone injection vs methylprednisolone for the treatment of refractory sudden sensorineural hearing loss. AB - BACKGROUND: During the past years various drugs have been used for sudden sensorineural hearing loss (SSNHL) treatment including steroids that are shown to be beneficial. Directed delivery of high doses of steroids into the inner ear is suggested for its potential and known as intratympanic steroids therapy (IST). Despite the use of dexamethasone and methylprednisolone as the traditional treatments, there are still debates about the optimal dosage, preferred drug, and the route of administration. MATERIALS AND METHODS: We performed a randomized clinical trial study in which 50 patients suffering from SSNHL and resistant to standard therapy were employed. Each patient took 0.5 ml methylprednisolone (40 mg/mg) along with bicarbonate or dexamethasone (4 mg/mL) through direct intratympanic injection. This method was performed and scheduled once every 2 days for three times only for the dexamethasone receiving group. Hearing test was carried out and the results were analyzed according to a four-frequency (0.5, 1.0, 2.0, 3.0 kHz) pure tone average (PTA) and Siegel's criteria. RESULTS: According to Siegel's criteria, three out of 25 (12%) dexamethasone receiving patients were healed in 1 and 4 (16%), 9 (32%) were respectively recovered in Siegel's criteria 2, 3, and 9 (32%) showed no recovery. In the group receiving methylprednisolone, recovery was found in 6 (24%), 8 (32%), 7 (28%) patients in the Siegel's criteria 1, 2, 3, respectively, and in 4 (16%) patients no recovery was recorded. In methylprednisolone group, hearing was significantly improved compared to the dexamethasone group (P < 0.05). The general hearing improvement rate was 84% in methylprednisolone receiving patients showing a significantly higher improvement than 64% in the dexamethasone group. CONCLUSIONS: Topical intratympanic treatment with methylprednisolone is safe and an effective treatment approach for those SSNHL cases that are refractory to the common therapies by Dexamethasone. PMID- 27403407 TI - Evaluation of prostatic cancer prevalence in patients with prostatic-specific antigen between 4 and 10 and normal digital rectal examination. AB - BACKGROUND: Prostate cancer is one of the most common male cancers. The prevalence of prostate cancer is different due to genetic and environmental factors. Diagnosis of prostate cancer is by biopsy due to prostate-specific antigen (PSA) and Digital Rectal Examination (DRE). Controversy about decision making for prostate biopsy in PSA between 4 and 10 and normal DRE, is one of the problems in this time. In this study we evaluated the prevalence of prostate cancer in males with PSA between 4 and 10 and normal DRE. We also evaluated the PSA density and percent of free PSA in patients with prostate cancer. MATERIALS AND METHODS: A total of 121 males with PSA between 4 and 10 and normal DRE, were evaluated. Then, transrectal ultrasonography (TRUS) andprostate biopsy from 12 points of peripheral zone, was done. These data were analyzed by Chi-square, t test and ANOVA and Roc curve. RESULTS: In this study, the prevalence of prostate cancer in PSA between 4 and 10 and normal DRE, was evaluated, 29.8%. With use of Roc curve, PSA density cutoff point was calculated 0.12 and percent of free PSA cutoff point, was calculated, 18%. CONCLUSION: In males with PSA between 4 and 10 and normal DRE, PSA density smaller than 0.12-0.15, and percent of free PSA greater than 18%, the prevalence of prostate cancer is very few and we can safely ignore the TRUS and prostate biopsy in these males and eliminate its costs and side effects. PMID- 27403408 TI - Qualitative indices and enhancement rate of CT pulmonary angiography in patients with suspected pulmonary embolism: Comparison between test bolus and bolus tracking methods. AB - BACKGROUND: The aim of the present study was to assess the qualitative indices and enhancement rate of computed tomographic pulmonary angiography (CTPA) in patients with suspected pulmonary embolism using Test bolus and Bolus-tracking techniques. MATERIALS AND METHODS: Fifty-two patients with suspected pulmonary embolism that passed informed consent were randomly divided in the two groups. In each group, demographic characteristics, qualitative indices, and enhancement rate of CTPA were recorded. RESULTS: The diagnostic result obtained in majority of the participants in the two groups (88.5 % in Test bolus group vs. 73.1% in the Bolus tracking group). In the case of quantitative variables, no statistically significant differences were found between the groups (P > 0.05). The only statistically significant difference between the two groups is average of "X-ray dose". CONCLUSION: The results of our study show that there is no statistically significant difference between the Bolus Tracking and Test Bolus techniques for producing more homogeneous enhancement. PMID- 27403409 TI - Comparison between paracetamol, piroxicam, their combination, and placebo in postoperative pain management of upper limb orthopedic surgery (a randomized double blind clinical trial). AB - BACKGROUND: Therapeutic superiority of a combination of Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) over either drug alone remains controversial. We evaluated the efficiency of a combination of Paracetamol and Piroxicam versus each drug alone and also placebo in the management of postoperative pain, in patients who had undergone elective upper limb orthopedic surgery under general anesthesia. MATERIALS AND METHODS: A total of 100 patients were randomly divided into four groups to receive either intravenous (IV) infusion of Paracetamol, 15 mg/kg., intramuscular (IM) injection of Piroxicam 0.4 mg/kg., their combination or placebo. The pain scores were recorded at the first; second, fourth, sixth, twelfth, and 24 hours after Post Anesthesia Care Unit (PACU) admission. After the operation 0.1 mg/kg of morphine was administered, if the patient needed. RESULT: The means of the pain scores were 5.26 +/- 1.53, 4.09 +/- 0.88, 4.36 +/- 1.48, and 4.11 +/- 1.29, in groups A, B, C, and D, respectively, (Group A: received placebo; Group B: received both Paracetamol and Piroxicam; Group C received Piroxicam; Group D received Paracetamol). Except for differences between the mean pain scores in Groups B and D, the other differences were statistically significant (P value < 0.05). No adverse effect was reported in the four groups. CONCLUSION: IV infusion of 15 mg/kg Paracetamol used as a preventive may provide effective analgesia in comparison with IM 0.4 mg/kg Piroxicam or placebo. Addition of Piroxicam to Paracetamol has not much more benefit than Paracetamol alone, in reducing pain after upper limb orthopedic surgery. PMID- 27403410 TI - Nutrition and Cancer. PMID- 27403411 TI - Feeding Challenges in Patients with Esophageal and Gastroesophageal Cancers. AB - BACKGROUND: Patients undergoing treatment for esophagogastric or esophageal cancer are exposed to a considerably high risk of malnutrition due to early obstruction of the gastrointestinal passage. Presently most of the patients undergo modern multimodal therapies which require chemoradiation or chemotherapy ahead of surgery. Therefore reconstruction of the obstructed gastrointestinal passage is considerably delayed. Surgery as the only curative option after neoadjuvant treatment is the mainstay of therapy in this setting. However, many patients are at risk for the development of postoperative complications associated with the complexity of the surgical procedure. Therefore enteral feeding as a prerequisite to avoid malnutrition represents a special therapeutic challenge. SUMMARY: This review describes the recent literature on the incidence and influence of perioperative malnutrition on oncologic outcome, measures to determine patients at risk, possible strategies to reduce or avoid malnutrition by supportive enteral/parenteral nutrition, implementation of the enhanced recovery after surgery programs and feeding routes, but also surgical and adjuvant procedures in the curative and palliative setting for patients undergoing treatment for gastroesophageal cancers. KEY MESSAGES: Appropriate identification of patients at risk is crucial to avoid malnutrition. Early nutritional interventions during multimodal/neoadjuvant treatment may be beneficial for weight loss reduction although the evidence is not conclusive. Pouch reconstructions during surgery should be applied in order to increase quality of life and eating capacity. Reduction of postoperative complications could provide potential benefits. In palliative patients, insertion of self expanding metal stents can reduce dysphagia and improve quality of life, but does not prolong overall survival. Further evidence is required to determine the value of the procedures and measures described in this review. PRACTICAL IMPLICATIONS: Nutritional risk scoring should be performed for every gastroesophageal cancer patient. Sophisticated reconstruction methods and early recovery programs should be enforced to reduce perioperative starvation periods. Self-expanding metal stents should be used for palliative patients. PMID- 27403412 TI - Nutrition in Patients with Gastric Cancer: An Update. AB - BACKGROUND: Nutritional management of patients with gastric cancer (GC) represents a challenge. SUMMARY: This review provides an overview of the present evidence on nutritional support in patients with GC undergoing surgery as well as in those with advanced disease. KEY MESSAGE: For patients undergoing surgery, the preoperative nutritional condition directly affects postoperative prognosis, overall survival and disease-specific survival. Perioperative nutritional support enriched with immune-stimulating nutrients reduces overall complications and hospital stay but not mortality after major elective gastrointestinal surgery. Early enteral nutrition after surgery improves early and long-term postoperative nutritional status and reduces the length of hospitalization as well. Vitamin B12 and iron deficiency are common metabolic sequelae after gastrectomy and warrant appropriate replacement. In malnourished patients with advanced GC, short-term home complementary parenteral nutrition improves the quality of life, nutritional status and functional status. Total home parenteral nutrition represents the only modality of caloric intake for patients with advanced GC who are unable to take oral or enteral nutrition. PRACTICAL IMPLICATIONS: Early evaluations of nutritional status and nutritional support represent key aspects in the management of GC patients with both operable and advanced disease. PMID- 27403413 TI - Nutrition and Hepatocellular Cancer. AB - BACKGROUND: Hepatocellular carcinoma (HCC) significantly contributes to the global burden of cancer. Liver cancer is the third most frequent cause of cancer related death with HCC representing more than 90% of primary liver cancers. The majority of patients are not only affected by the malignant disease but do also suffer from chronic liver disease. Therefore, several factors impact on the prognosis of patients with HCC, including tumor-related factors, liver function and patient-related factors such as performance status and other comorbidities. The nutritional status is of high significance for the patients' performance status, the tolerance of tumor-targeting therapy and the prognosis of cancer of any type and is specially referenced in HCC. This overview is on current concepts on the role of nutritional factors in hepatocarcinogenesis and the role of nutrition in patients affected by HCC. SUMMARY: Nutritional status and composition of diet are relevant factors related to the risk of HCC. They also have an important role concerning the prognosis of patients with HCC. Besides risk factors, several macro- and micronutrient components have been found to be inversely correlated with the risk of HCC. To prevent disease progression to liver cirrhosis or HCC in patients with nonalcoholic steatohepatitis, it is crucial to optimize the metabolic state. KEY MESSAGE AND PRACTICAL IMPLICATION: Evidence from well-designed prospective interventional trials with the aim to reduce the HCC incidence or to prolong survival in patients with HCC based on nutritional modification is still to be generated. PMID- 27403414 TI - Nutrition in Pancreatic Cancer: A Review. AB - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. SUMMARY: This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival. KEY MESSAGE: Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data. PRACTICAL IMPLICATIONS: Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and l carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer. PMID- 27403415 TI - Nutrients Impact the Pathogenesis and Development of Colorectal Cancer. AB - BACKGROUND: Colorectal cancer is a commonly diagnosed cancer and the cause of many cancer deaths worldwide. Nutrients might be crucial in the pathogenesis and development of colorectal cancer. Although a number of studies have demonstrated the potential effects of nutrients, many challenges still remain. SUMMARY: A tremendous amount of research has emerged concerning the roles of nutrients in colorectal cancer during the past decades. Here, we review the latest research progress on nutrients, including vitamins, folic acid, calcium, selenium and dietary fiber, involved in colorectal cancer prevention. KEY MESSAGE: Nutrients are commonly consumed in foods or dietary supplements. It is clear that nutrients could play an important role and influence colorectal cancer outcomes. The relationship between nutrients and colorectal risk is complex. Vitamins, folic acid, calcium, selenium and dietary fiber have been proposed as potential agents to prevent colorectal cancer. However, some studies found that these nutrients did not reduce the incidence of colorectal cancer. PRACTICAL IMPLICATIONS: The supplementary dose of nutrients, the length of time required to observe the effects and confounding factors during the study might influence the role of nutrients in the prevention of colorectal cancer. Therefore, more evidence from ongoing clinical trials with different population groups and longer follow-up periods is critical to determine the relationship between nutrients and colorectal cancer. PMID- 27403416 TI - Crosstalk between Vitamin D Metabolism, VDR Signalling, and Innate Immunity. AB - The primary function of vitamin D is to regulate calcium homeostasis, which is essential for bone formation and resorption. Although diet is a source of vitamin D, most foods are naturally lacking vitamin D. Vitamin D is also manufactured in the skin through a photolysis process, leading to a process called the "sunshine vitamin." The active form of vitamin D, 1,25-dihydroxyvitamin D (calcitriol), is biosynthesised in the kidney through the hydroxylation of 25 hydroxycholecalciferol by the CYP27B1 enzyme. It has been found that several immune cells express the vitamin D receptor (VDR) and CYP27B1; of the latter, synthesis is determined by several immune-specific signals. The realisation that vitamin D employs several molecular mechanisms to regulate innate immune responses is more recent. Furthermore, evidence collected from intervention studies indicates that vitamin D supplements may boost clinical responses to infections. This review considers the current knowledge of how immune signals regulate vitamin D metabolism and how innate immune system function is modulated by ligand-bound VDR. PMID- 27403417 TI - Metformin Alleviated Abeta-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons. AB - Both diabetes and hyperinsulinemia are confirmed risk factors for Alzheimer's disease. Some researchers proposed that antidiabetic drugs may be used as disease modifying therapies, such as metformin and thiazolidinediones, although more evidence was poorly supported. The aim of the current study is to investigate the role of metformin in Abeta-induced cytotoxicity and explore the underlying mechanisms. First, the experimental results show that metformin salvaged the neurons exposed to Abeta in a concentration-dependent manner with MTT and LDH assay. Further, the phosphorylation levels of JNK, ERK1/2, and p38 MAPK were measured with western blot analysis. It was investigated that Abeta increased phospho-JNK significantly but had no effect on phospho-p38 MAPK and phospho ERK1/2. Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way. In addition, it was observed that metformin protected the neurons via the suppression of apoptosis. Taken together, our findings demonstrate that metformin may have a positive effect on Abeta-induced cytotoxicity, which provides a preclinical strategy against AD for elders with diabetes. PMID- 27403418 TI - Distinct Expression Pattern of a Deafness Gene, KIAA1199, in a Primate Cochlea. AB - Deafness is one of the most common types of congenital impairments, and at least half of the cases are caused by hereditary mutations. Mutations of the gene KIAA1199 are associated with progressive hearing loss. Its expression is abundant in human cochlea, but interestingly the spatial expression patterns are different between mouse and rat cochleae; the pattern in humans has not been fully investigated. We performed immunohistochemical analysis of a nonhuman primate, common marmoset (Callithrix jacchus), cochlea with a KIAA1199-specific antibody. In the common marmoset cochlea, KIAA1199 protein expression was more widespread than in rodents, with all epithelial cells, including hair cells, expressing KIAA1199. Our results suggest that the primate pattern of KIAA1199 expression is wider in comparison with rodents and may play an essential role in the maintenance of cochlear epithelial cells. PMID- 27403420 TI - Inverse Kinematics for Upper Limb Compound Movement Estimation in Exoskeleton Assisted Rehabilitation. AB - Robot-Assisted Rehabilitation (RAR) is relevant for treating patients affected by nervous system injuries (e.g., stroke and spinal cord injury). The accurate estimation of the joint angles of the patient limbs in RAR is critical to assess the patient improvement. The economical prevalent method to estimate the patient posture in Exoskeleton-based RAR is to approximate the limb joint angles with the ones of the Exoskeleton. This approximation is rough since their kinematic structures differ. Motion capture systems (MOCAPs) can improve the estimations, at the expenses of a considerable overload of the therapy setup. Alternatively, the Extended Inverse Kinematics Posture Estimation (EIKPE) computational method models the limb and Exoskeleton as differing parallel kinematic chains. EIKPE has been tested with single DOF movements of the wrist and elbow joints. This paper presents the assessment of EIKPE with elbow-shoulder compound movements (i.e., object prehension). Ground-truth for estimation assessment is obtained from an optical MOCAP (not intended for the treatment stage). The assessment shows EIKPE rendering a good numerical approximation of the actual posture during the compound movement execution, especially for the shoulder joint angles. This work opens the horizon for clinical studies with patient groups, Exoskeleton models, and movements types. PMID- 27403419 TI - Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development. AB - The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC) and acid sensitive ionic channel (ASIC). ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na(+)) across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics. PMID- 27403421 TI - Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression. AB - Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect. PMID- 27403422 TI - Histological Lesions and Cellular Response in the Skin of Alpine Chamois (Rupicapra r. rupicapra) Spontaneously Affected by Sarcoptic Mange. AB - Population dynamics of chamois (genus Rupicapra, subfamily Caprinae) can be influenced by infectious diseases epizootics, of which sarcoptic mange is probably the most severe in the Alpine chamois (Rupicapra rupicapra rupicapra). In this study, skin lesions and cellular inflammatory infiltrates were characterized in 44 Alpine chamois affected by sarcoptic mange. Dermal cellular responses were evaluated in comparison with chamois affected by trombiculosis and controls. In both sarcoptic mange and trombiculosis, a significantly increase of eosinophils, mast cells, T and B lymphocytes, and macrophages was detected. Moreover, in sarcoptic mange significant higher numbers of T lymphocytes and macrophages compared to trombiculosis were observed. Lesions in sarcoptic mange were classified in three grades, according to crusts thickness, correlated with mite counts. Grade 3 represented the most severe form with crust thickness more than 3.5 mm, high number of mites, and severe parakeratosis with diffuse bacteria. Evidence of immediate and delayed hypersensitivity was detected in all three forms associated with diffuse severe epidermal hyperplasia. In grade 3, a significant increase of B lymphocytes was evident compared to grades 1 and 2, while eosinophil counts were significantly higher than in grade 1, but lower than in grade 2 lesions. An involvement of nonprotective Th2 immune response could in part account for severe lesions of grade 3. PMID- 27403423 TI - Outcomes and National Trends for the Surgical Treatment of Lumbar Spine Trauma. AB - Introduction. Operative treatment of lumbar spine compression fractures includes fusion and/or cement augmentation. Our aim was to evaluate postoperative differences in patients treated surgically with fusion, vertebroplasty, or kyphoplasty. Methods. The Nationwide Inpatient Sample Database search for adult vertebral compression fracture patients treated 2004-2011 identified 102,316 surgical patients: 30.6% underwent spinal fusion, 17.1% underwent kyphoplasty, and 49.9% underwent vertebroplasty. Univariate analysis of patient and hospital characteristics, by treatment, was performed. Multivariable analysis was used to determine factors associated with mortality, nonroutine discharge, complications, and patient safety. Results. Average patient age: fusion (46.2), kyphoplasty (78.5), vertebroplasty (76.7) (p < .0001). Gender, race, household income, hospital-specific characteristics, and insurance differences were found (p <= .001). Leading comorbidities were hypertension, osteoporosis, and diabetes. Risks for higher mortality (OR 2.0: CI: 1.6-2.5), nonroutine discharge (OR 1.6, CI: 1.6 1.7), complications (OR 1.1, CI: 1.0-1.1), and safety related events (OR 1.1, CI: 1.0-1.1) rose consistently with increasing age, particularly among fusion patients. Preexisting comorbidities and longer in-hospital length of stay were associated with increased odds of nonroutine discharge, complications, and patient safety. Conclusions. Fusion patients had higher rates of poorer outcomes compared to vertebroplasty and kyphoplasty cohorts. Mortality, nonroutine discharge, complications, and adverse events increased consistently with older age. PMID- 27403424 TI - Influence of Trabecular Bone on Peri-Implant Stress and Strain Based on Micro-CT Finite Element Modeling of Beagle Dog. AB - The objective of this investigation is to analyze the influence of trabecular microstructure modeling on the biomechanical distribution of the implant-bone interface. Two three-dimensional finite element mandible models, one with trabecular microstructure (a refined model) and one with macrostructure (a simplified model), were built. The values of equivalent stress at the implant bone interface in the refined model increased compared with those of the simplified model and strain on the contrary. The distributions of stress and strain were more uniform in the refined model of trabecular microstructure, in which stress and strain were mainly concentrated in trabecular bone. It was concluded that simulation of trabecular bone microstructure had a significant effect on the distribution of stress and strain at the implant-bone interface. These results suggest that trabecular structures could disperse stress and strain and serve as load buffers. PMID- 27403425 TI - Development of Alginate Microspheres Containing Chuanxiong for Oral Administration to Adult Zebrafish. AB - Oral administration of Traditional Chinese Medicine (TCM) by patients is the common way to treat health problems. Zebrafish emerges as an excellent animal model for the pharmacology investigation. However, the oral delivery system of TCM in zebrafish has not been established so far. This issue was addressed by development of alginate microparticles for oral delivery of chuanxiong, a TCM that displays antifibrotic and antiproliferative effects on hepatocytes. The delivery microparticles were prepared from gelification of alginate containing various levels of chuanxiong. The chuanxiong-encapsulated alginate microparticles were characterized for their solubility, structure, encapsulation efficiency, the cargo release profile, and digestion in gastrointestinal tract of zebrafish. Encapsulation of chuanxiong resulted in more compact structure and the smaller size of microparticles. The release rate of chuanxiong increased for alginate microparticles carrying more chuanxiong in simulated intestinal fluid. This remarkable feature ensures the controlled release of encapsulated cargos in the gastrointestinal tract of zebrafish. Moreover, chuanxiong-loaded alginate microparticles were moved to the end of gastrointestinal tract after oral administration for 6 hr and excreted from the body after 16 hr. Therefore, our developed method for oral administration of TCM in zebrafish is useful for easy and rapid evaluation of the drug effect on disease. PMID- 27403426 TI - Aberrant Resting-State Functional Connectivity Density in Patients with Hepatitis B Virus-Related Cirrhosis. AB - There is increasing evidence that cirrhosis may affect functional connectivity among various brain regions in patients prior to onset of overt hepatic encephalopathy (HE). However, most investigators have focused mainly on alterations in functional connectivity strengths, and the changes in functional connectivity density (FCD) are largely unknown. Here, we investigated alterations in resting-state FCD in patients with hepatitis B virus-related cirrhosis (HBV RC) without overt HE. Totally, 31 patients with HBV-RC without overt HE and 30 age- and sex-matched healthy controls underwent resting-state functional MRI examinations. FCD mapping was employed to compute local and global FCD maps. Then, short-range and long-range FCD values were calculated and voxel-based comparisons were performed between the two groups. The HBV-RC group showed significant decreases in FCD, including decreased short-range FCDs in the bilateral middle cingulum gyrus/precuneus, the bilateral cuneus, and the left lingual gyrus/inferior occipital gyrus and decreased long-range FCD in the bilateral cuneus/precuneus. In addition, the decreased long-range FCD in the bilateral cuneus/precuneus in the HBV-RC group was related to performance on the psychometric hepatic encephalopathy score (PHES) test. These findings suggest aberrant functional connectivity density in cirrhotic patients prior to overt HE onset, which may provide better insight into understanding the pathophysiological mechanisms underlying the cirrhotic-related cognitive impairment. PMID- 27403428 TI - Segmentation of MRI Brain Images with an Improved Harmony Searching Algorithm. AB - The harmony searching (HS) algorithm is a kind of optimization search algorithm currently applied in many practical problems. The HS algorithm constantly revises variables in the harmony database and the probability of different values that can be used to complete iteration convergence to achieve the optimal effect. Accordingly, this study proposed a modified algorithm to improve the efficiency of the algorithm. First, a rough set algorithm was employed to improve the convergence and accuracy of the HS algorithm. Then, the optimal value was obtained using the improved HS algorithm. The optimal value of convergence was employed as the initial value of the fuzzy clustering algorithm for segmenting magnetic resonance imaging (MRI) brain images. Experimental results showed that the improved HS algorithm attained better convergence and more accurate results than those of the original HS algorithm. In our study, the MRI image segmentation effect of the improved algorithm was superior to that of the original fuzzy clustering method. PMID- 27403427 TI - Functional Characterization of 9-/13-LOXs in Rice and Silencing Their Expressions to Improve Grain Qualities. AB - Lipoxygenases (LOXs) are involved in oxidative rancidity and render rice unsuitable for human consumption. Here, RNA interference- (RNAi-) induced gene expression inhibition was used to analyze the functions of the bran/seed-specific LOXs in rice. r9-LOX1 and L-2 (9-LOX category) were the candidate genes expressing a bran/seed-specific LOX, while RCI-1 was (13-LOX category) a plastid specific LOX. Real-time PCR showed that three LOXs were cultivar/tissue specific expression on a certain level. r9-LOX1 and L-2 were generally much higher in active bran/seed than in stabilized bran, mature seed, and regenerated plant. RCI 1 was barely expressed in seed. In transgenic lines, r9-LOX1, as well as L-2, expression was dramatically downregulated, compared to the nontransgenic controls. SPME/GC-MS analysis of r9-LOX1 RNAi transgenic lines showed 74.33% decrease in nonanal content (formed during oxidation of linoleic acid by lipoxygenase), but 388.24% increase in acetic acid and 184.84% hexanal (direct products of 13-LOX). These results indicate that r9-LOX1 positively regulates the amount of nonanal but negatively regulates acetic acid and hexanal. The negative regulation may be due to a mechanism of negative feedback between LOX family members. The information will help comprehensively understand the function of the bran/seed-specific LOXs, r9-LOX1, and improve the storage quality in the future. PMID- 27403429 TI - L-Malate's Plasma and Excretion Profile in the Treatment of Moderate and Severe Hemorrhagic Shock in Rats. AB - Introduction. Malate is a standard component in fluid therapy within a wide range of medical applications. To date, there are insufficient data regarding its plasma distribution, renal excretion, and metabolism after infusion. This study aimed to investigate these three aspects in a rat model of moderate and severe hemorrhagic shock (HS). Methods. Male Wistar rats were subjected to HS by dropping the mean arterial blood pressure to 25-30 mmHg (severe) and 40-45 mmHg (moderate), respectively, for 60 minutes. Subsequently, reperfusion with Ringer saline or a malate containing crystalloid solution (7 mM, 13.6 mM, and 21 mM, resp.) was performed within 30 minutes, followed by an observation period of 150 minutes. Results. In the present experiments, malate rapidly disappeared from the blood, while only 5% of the infused malate was renally excreted. In the resuscitation interval the urinary citrate and succinate amounts significantly increased compared to control. Conclusion. Malate's half-life is between 30 and 60 minutes in both, moderate and severe HS. Thus, even under traumatic conditions malate seems to be subjected to rapid metabolism with participation of the kidneys. PMID- 27403430 TI - Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells. AB - Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale up of hepatic three-dimensional culture models for regenerative medicine applications. PMID- 27403432 TI - Turning Disaster into an Opportunity for Quality Improvement in Essential Intrapartum and Newborn Care Services in the Philippines: Pre- to Posttraining Assessments. AB - Background. On 8 November 2013, supertyphoon Haiyan made landfall in the Philippines, severely disrupting health service delivery. Reestablishment of essential services for birthing mothers and their newborns became high priority. Methodology. Following a baseline assessment, an Essential Intrapartum and Newborn Care (EINC) training package was implemented and posttraining assessments (1 and 3 months after training) were undertaken. Results. Baseline assessments (n = 56 facilities) revealed gaps in provider's skill and shortage of life-saving commodities. Facilities lacked newborn bags/masks (9%), towels (6%), and magnesium sulfate (39%). Service providers lacked skills in partograph use (54%), antenatal steroid (44%) use, and breastfeeding initiation (50%). At 3 months after training (n = 51 facilities), dramatic increases in correct partograph use (to 92%), antenatal steroid use (to 98%), breastfeeding initiation (to 86%), kangaroo mother care (to 94%), availability of magnesium sulfate (to 94%), and bag/masks (to 88%) were documented. Gaps persisted for skills in assisted vaginal delivery and removal of placental fragments. Conclusion. Health services were severely disrupted after supertyphoon Haiyan. Our study demonstrates that essential birthing services and quality improvements to strengthen local health systems can be restored in a timely manner even in immediate postdisaster settings. PMID- 27403433 TI - Acute Aortic Dissection Biomarkers Identified Using Isobaric Tags for Relative and Absolute Quantitation. AB - The purpose of this study was to evaluate the utility of potential serum biomarkers for acute aortic dissection (AAD) that were identified by isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approaches. Serum samples from 20 AAD patients and 20 healthy volunteers were analyzed using iTRAQ technology. Protein validation was performed using samples from 120 patients with chest pain. A total of 355 proteins were identified with the iTRAQ approach; 164 proteins reached the strict quantitative standard, and 125 proteins were increased or decreased more than 1.2-fold (64 and 61 proteins were up- and downregulated, resp.). Lumican, C-reactive protein (CRP), thrombospondin-1 (TSP 1), and D-dimer were selected as candidate biomarkers for the validation tests. Receiver operating characteristic (ROC) curves show that Lumican and D-dimer have diagnostic value (area under the curves [AUCs] 0.895 and 0.891, P < 0.05). For Lumican, the diagnostic sensitivity and specificity were 73.33% and 98.33%, while the corresponding values for D-dimer were 93.33% and 68.33%. For Lumican and D dimer AAD combined diagnosis, the sensitivity and specificity were 88.33% and 95%, respectively. In conclusion, Lumican has good specificity and D-dimer has good sensitivity for the diagnosis of AAD, while the combined detection of D dimer and Lumican has better diagnostic value. PMID- 27403434 TI - Prediction of Small Bowel Obstruction Caused by Bezoars Using Risk Factor Categories on Multidetector Computed Tomographic Findings. AB - Objectives. The aim of this study was to detect factors associated with small bowel obstruction (SBO) caused by bezoars on multidetector computed tomographic findings. Methods. We retrospectively reviewed 61 patients who had bezoars in the small bowels on MDCT. The patients were divided into SBO patients group and non SBO patients group. The mean values of the diameter, volume, and CT attenuation as well as location and characteristics of the bezoars were compared between the two groups. Multivariate analysis was performed to determine factors associated with SBO. Results. There were 32 patients (52.5%) in the SBO group and 29 patients (47.5%) in the non-SBO group. The bezoars in the SBO group had greater values of each mean diameter and mean volume than those in the non-SBO group (3.2 +/- 0.5 cm versus 1.6 +/- 0.7 cm, P < 0.0001, 14.9 +/- 6.4 cm(3) versus 2.5 +/- 2.7 cm(3), P < 0.0001, resp.) and had a lower CT attenuation than the non-SBO group (55.5 +/- 23.4 versus 173.0 +/- 68.0, P < 0.0001). The SBO group had higher prevalence of phytobezoar appearance (75.0% versus 10.3%, P < 0.0001). Major diameters of bezoar and phytobezoar were significant independent risk factors associated with SBO (odds ratio = 36.09, 8.26, resp., and P = 0.0004, 0.044, resp.). Conclusions. Major diameter of bezoar or phytobezoar is a potential risk factor associated with SBO. PMID- 27403431 TI - Multi-OMICs and Genome Editing Perspectives on Liver Cancer Signaling Networks. AB - The advent of the human genome sequence and the resulting ~20,000 genes provide a crucial framework for a transition from traditional biology to an integrative "OMICs" arena (Lander et al., 2001; Venter et al., 2001; Kitano, 2002). This brings in a revolution for cancer research, which now enters a big data era. In the past decade, with the facilitation by next-generation sequencing, there have been a huge number of large-scale sequencing efforts, such as The Cancer Genome Atlas (TCGA), the HapMap, and the 1000 genomes project. As a result, a deluge of genomic information becomes available from patients stricken by a variety of cancer types. The list of cancer-associated genes is ever expanding. New discoveries are made on how frequent and highly penetrant mutations, such as those in the telomerase reverse transcriptase (TERT) and TP53, function in cancer initiation, progression, and metastasis. Most genes with relatively frequent but weakly penetrant cancer mutations still remain to be characterized. In addition, genes that harbor rare but highly penetrant cancer-associated mutations continue to emerge. Here, we review recent advances related to cancer genomics, proteomics, and systems biology and suggest new perspectives in targeted therapy and precision medicine. PMID- 27403435 TI - Molecular Diagnosis and Identification of Leishmania Species in Jordan from Saved Dry Samples. AB - Diagnosis of the endemic cutaneous leishmaniasis (CL) in Jordan relies on patient clinical presentation and microscopic identification. Studies toward improved identification of the causative Leishmania species, especially in regions where multiple species exist, and the introduction of these techniques into medical diagnosis is paramount. This study looked at the current epidemiology of CL in Jordan. Clinically diagnosed 41 patients with CL were tested for the presence of Leishmania parasite using both Giemsa staining from skin scraps on glass slides and ITS1-PCR from samples blotted onto storage cards (NucleoCards(r)). Microscopically, 28 out of the 41 (68.3%) collected samples were positive for amastigotes, whereas the molecular ITS1-PCR amplification successfully identified 30 of the 41 samples (73.2%). Furthermore, PCR-RFLP analysis allowed species identification which is impossible microscopically. Of the 30 PCR positive samples, 28 were Leishmania major positive and the other two samples were Leishmania tropica. This indicates that L. major is the most prevalent species in Jordan and the two L. tropica cases originated from Syria indicating possible future L. tropica outbreaks. Diagnosis of CL based on clinical presentation only may falsely increase its prevalence. Although PCR is more sensitive, it is still not available in our medical laboratories in Jordan. PMID- 27403436 TI - Usefulness of Multiplex Real-Time PCR for Simultaneous Pathogen Detection and Resistance Profiling of Staphylococcal Bacteremia. AB - Staphylococci are the leading cause of nosocomial blood stream infections. Fast and accurate identification of staphylococci and confirmation of their methicillin resistance are crucial for immediate treatment with effective antibiotics. A multiplex real-time PCR assay that targets mecA, femA specific for S. aureus, femA specific for S. epidermidis, 16S rRNA for universal bacteria, and 16S rRNA specific for staphylococci was developed and evaluated with 290 clinical blood culture samples containing Gram-positive cocci in clusters (GPCC). For the 262 blood cultures identified to the species level with the MicroScan WalkAway system (Siemens Healthcare Diagnostics, USA), the direct real-time PCR assay of positive blood cultures showed very good agreement for the categorization of staphylococci into methicillin-resistant S. aureus (MRSA), methicillin susceptible S. aureus (MSSA), methicillin-resistant S. epidermidis (MRSE), methicillin-susceptible S. epidermidis (MSSE), methicillin-resistant non-S. epidermidis CoNS (MRCoNS), and methicillin-susceptible non-S. epidermidis CoNS (MSCoNS) (kappa = 0.9313). The direct multiplex real-time PCR assay of positive blood cultures containing GPCC can provide essential information at the critical point of infection with a turnaround time of no more than 4 h. Further studies should evaluate the clinical outcome of using this rapid real-time PCR assay in glycopeptide antibiotic therapy in clinical settings. PMID- 27403437 TI - Poly-L-lysine Prevents Senescence and Augments Growth in Culturing Mesenchymal Stem Cells Ex Vivo. AB - Mesenchymal stem cells (MSCs) possess great therapeutic potential. Efficient in vitro expansion of MSCs is however necessary for their clinical application. The extracellular matrix (ECM) provides structural and biochemical support to the surrounding cells, and it has been used as a coating substrate for cell culture. In this study, we have aimed to improve the functionality and stemness of MSCs during culture using poly-L-lysine (PLL). Functionality of MSCs was analysed by cell cycle analysis, differentiation assay, beta-galactosidase staining, and RT PCR. Furthermore, we assessed the global gene expression profile of MSCs on uncoated and PLL-coated plates. MSCs on PLL-coated plates exhibited a faster growth rate with increased S-phase and upregulated expression of the stemness markers. In addition, their osteogenic differentiation potential was increased, and genes involved in cell adhesion, FGF-2 signalling, cell cycle, stemness, cell differentiation, and cell proliferation were upregulated, compared to that of the MSCs cultured on uncoated plates. We also confirmed that MSCs on uncoated plates expressed higher beta-galactosidase than the MSCs on PLL-coated plates. We demonstrate that PLL provides favourable microenvironment for MSC culture by reversing the replicative senescence. This method will significantly contribute to effective preparation of MSCs for cellular therapy. PMID- 27403438 TI - Clinical Significance of miR-149 in the Survival of Patients with Laryngeal Squamous Cell Carcinoma. AB - MicroRNAs (miRNAs) play critical roles in the progression of laryngeal cancer (LC). In this study, we aimed to investigate whether miR-149 is associated with the prognosis of patients with LC. A total of 97 laryngeal squamous cell carcinoma patients who underwent tumor resection were included in our follow-up study. In vitro studies was performed in cancer cell line Hep-2 to explore the antitumor role of miR-149 in LC. We found that the expression of miR-149 was significantly lower in tumor tissues, compared with vocal cord polyp tissues (P < 0.05). Kaplan-Meier analysis revealed that miR-149 expression status is significantly associated with survival duration (log rank test, P < 0.05), and multivariate Cox regression analysis revealed that patients with low miR-149 expression had shorter survival times compared with patients with high miR-149 expression. In vitro studies revealed that the exogenous expression of miRNA-149 inhibits the proliferation of human Hep-2 cells and induces cell apoptosis. Our study suggests that miR-149 expression in laryngeal squamous cell carcinoma tissues is critically associated with the prognosis of patients, and the ectopic expression of miR-149 in Hep-2 cells inhibits proliferation and cell cycle progression. PMID- 27403439 TI - Research Progress on Chemical Constituents of Lonicerae japonicae flos. AB - Lonicerae japonicae flos is commonly used in traditional Chinese medicine for thousands of years with confirmed curative effects. Except for medicine, it is also used in healthy food, cosmetics, and soft beverages for its specific activities. Therefore, the chemical constituents, mainly including organic acids, flavonoids, iridoids, triterpenoids, and volatile oils, have been well studied by many scholars in recent years and a comprehensive and systematic review on chemical constituents of Lonicerae japonicae flos is indispensable. This paper aims at reviewing the chemical components of LJF in recent years through searching for the literatures both at home and abroad. Our results show that 212 components have been isolated from Lonicerae japonicae flos, including 27 flavonoids, 40 organic acids, 83 iridoids, 17 triterpenoids, and 45 other compounds, which could lay a foundation for the further application of Lonicerae japonicae flos. PMID- 27403440 TI - Platelet Activation: The Mechanisms and Potential Biomarkers. AB - Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory and immunomodulatory activities. Our knowledge about how platelets modulate inflammatory and immunity has greatly improved in recent years. In this review, we discuss recent advances in the pathways of platelet activation and potential application of platelet activation biomarkers to diagnosis and prediction of disease states. PMID- 27403441 TI - Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias. AB - Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs. PMID- 27403442 TI - Screening of Undiagnosed Hypothyroidism in Elderly Persons with Diabetes according to Age-Specific Reference Intervals for Serum Thyroid Stimulating Hormone and the Impact of Antidiabetes Drugs. AB - Background. Studies have suggested that hypothyroidism is more frequent in the elderly with diabetes mellitus. However, an adaptation of TSH levels to age should be considered in this assessment. Some antidiabetes drugs reportedly interfere with TSH levels. The objectives of this study were to evaluate the prevalence of undiagnosed hypothyroidism in patients with diabetes and the influence of antidiabetes drugs. Material and Methods. 1160 subjects, 60 years and older (751 with diabetes), were studied; results were compared according to diabetes treatment and with persons without diabetes. TSH, FT4, antithyroperoxidase, fasting glucose, and HbA1c were measured. Results and Discussion. 6.4% of patients with diabetes had hypothyroidism, a higher prevalence compared with persons without diabetes (5.1%), but lower than observed in many studies. The use of age-specific TSH reference interval (RI) could explain this difference. Patients taking metformin (MTF) had TSH (showed in medians) slightly lower (2.8 mU/L) than those not on MTF (3.3 mU/L), p < 0.05. MTF doses influenced TSH levels. Conclusions. The use of specific TSH RI could avoid the misdiagnosis of hypothyroidism in elderly with diabetes. Patients in use of MTF as single drug had lower TSH than those using other medications and persons without diabetes. PMID- 27403443 TI - The Relation between Serum Uric Acid and HbA1c Is Dependent upon Hyperinsulinemia in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. AB - Objective. The aim of our study was to explore the dependent condition of the relationship between uric acid and blood glucose in type 2 diabetes. Research Design and Methods. We measured the HbA1c, serum uric acid, creatinine, lipids profiles, and so forth of 605 newly diagnosed type 2 diabetes patients, and oral glucose tolerance tests (OGTTs) were performed on each patient. The population was divided into high and low insulin groups. Multiple linear regression analyses were conducted to assess the relationship between uric acid and HbA1c. Results. Serum uric acid and HbA1c levels were low in newly diagnosed type 2 diabetes patients. However, we found no significant relationship between uric acid and HbA1c by regression analysis after adjusting total insulin. The concentration of uric acid was inversely correlated with HbA1c in the high insulin group, regardless of patient sex. However, no associations were found in low insulin group. Conclusions. The negative correlation between uric acid and HbA1c is conditional in newly diagnosed type 2 diabetes patients and is related to hyperinsulinemia. Therefore, uric acid is likely only useful as a biomarker of blood glucose in patients exhibiting hyperinsulinemia. PMID- 27403444 TI - The Hospitalization Costs of Diabetes and Hypertension Complications in Zimbabwe: Estimations and Correlations. AB - Objective. Treating complications associated with diabetes and hypertension imposes significant costs on health care systems. This study estimated the hospitalization costs for inpatients in a public hospital in Zimbabwe. Methods. The study was retrospective and utilized secondary data from medical records. Total hospitalization costs were estimated using generalized linear models. Results. The median cost and interquartile range (IQR) for patients with diabetes, $994 (385-1553) mean $1319 (95% CI: 981-1657), was higher than patients with hypertension, $759 (494-1147) mean $914 (95% CI: 825-1003). Female patients aged below 65 years with diabetes had the highest estimated mean costs ($1467 (95% CI: 1177-1828)). Wound care had the highest estimated mean cost of all procedures, $2884 (95% CI: 2004-4149) for patients with diabetes and $2239 (95% CI: 1589-3156) for patients with hypertension. Age below 65 years, medical procedures (amputation, wound care, dialysis, and physiotherapy), the presence of two or more comorbidities, and being prescribed two or more drugs were associated with significantly higher hospitalization costs. Conclusion. Our estimated costs could be used to evaluate and improve current inpatient treatment and management of patients with diabetes and hypertension and determine the most cost-effective interventions to prevent complications and comorbidities. PMID- 27403445 TI - Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure. AB - Background. Chronic obstructive pulmonary disease (COPD) is a common, smoking related lung disease. Patients with COPD frequently suffer disease exacerbations induced by bacterial respiratory infections, suggestive of impaired innate immunity. Low-dose oxygen is a mainstay of therapy during COPD exacerbations; yet we understand little about whether oxygen can modulate the effects of cigarette smoke on lung immunity. Methods. Wild-type mice were exposed to cigarette smoke for 5 weeks, followed by intratracheal instillation of Pseudomonas aeruginosa (PAO1) and 21% or 35-40% oxygen. After two days, lungs were harvested for PAO1 CFUs, and bronchoalveolar fluid was sampled for inflammatory markers. In culture, macrophages were exposed to cigarette smoke and oxygen (40%) for 24 hours and then incubated with PAO1, followed by quantification of bacterial phagocytosis and inflammatory markers. Results. Mice exposed to 35-40% oxygen after cigarette smoke and PAO1 had improved survival and reduced lung CFUs and inflammation. Macrophages from these mice expressed less TNF-alpha and more scavenger receptors. In culture, macrophages exposed to cigarette smoke and oxygen also demonstrated decreased TNF-alpha secretion and enhanced phagocytosis of PAO1 bacteria. Conclusions. Our findings demonstrate a novel, protective role for low dose oxygen following cigarette smoke and bacteria exposure that may be mediated by enhanced macrophage phagocytosis. PMID- 27403446 TI - Expression of Pentraxin 3 and Thrombospondin 1 in Gingival Crevicular Fluid during Wound Healing after Gingivectomy in Postorthodontic Patients. AB - Background. Wound healing is a tissue repair process after an injury, and two of its main components are inflammation and angiogenesis, in which course a cascade of mediators is involved. The aim of this research was to evaluate the involvement of Pentraxin 3 and Thrombospondin 1 in wound healing after periodontal surgery (gingivectomy) for gingival overgrowth during orthodontic treatment with or without magnification devices, by assessing their levels in GCF. Methods. From 19 patients with gingival overgrowth as a result of fixed orthodontic treatment, the overgrown gingiva was removed by gingivectomy, from one half of the mandibular arch without magnification and from the other under magnification. Pentraxin 3 and Thrombospondin 1 were determined from gingival crevicular fluid by ELISA tests. Results. Statistically significant differences (p < 0.05) and correlations between levels of the two biomarkers were analyzed. Statistically significant differences were established between levels of the two biomarkers at different time points, with significant positive correlation at the point of 24 hours. Conclusions. Within the limitations of this study, the results seem to sustain the involvement of Pentraxin 3 and Thrombospondin 1 in the processes of inflammation and angiogenesis in wound healing of patients with postorthodontic gingivectomy. The dynamics of Pentraxin 3 and Thrombospondin 1 levels could suggest a reduced inflammation and a faster angiogenesis using microsurgery. PMID- 27403448 TI - Iterative-cuts: longitudinal and scale-invariant segmentation via user-defined templates for rectosigmoid colon in gynecological brachytherapy. AB - Among all types of cancer, gynecological malignancies belong to the fourth most frequent type of cancer among women. In addition to chemotherapy and external beam radiation, brachytherapy is the standard procedure for the treatment of these malignancies. In the progress of treatment planning, localization of the tumor as the target volume and adjacent organs of risks by segmentation is crucial to accomplish an optimal radiation distribution to the tumor while simultaneously preserving healthy tissue. Segmentation is performed manually and represents a time-consuming task in clinical daily routine. This study focuses on the segmentation of the rectum/sigmoid colon as an organ-at-risk in gynecological brachytherapy. The proposed segmentation method uses an interactive, graph-based segmentation scheme with a user-defined template. The scheme creates a directed two-dimensional graph, followed by the minimal cost closed set computation on the graph, resulting in an outlining of the rectum. The graph's outline is dynamically adapted to the last calculated cut. Evaluation was performed by comparing manual segmentations of the rectum/sigmoid colon to results achieved with the proposed method. The comparison of the algorithmic to manual result yielded a dice similarity coefficient value of [Formula: see text], in comparison to [Formula: see text] for the comparison of two manual segmentations by the same physician. Utilizing the proposed methodology resulted in a median time of [Formula: see text], compared to 300 s needed for pure manual segmentation. PMID- 27403449 TI - Enhanced resolution pulse-echo imaging with stabilized pulses. AB - Many pulse-echo imaging systems use focused beams to improve lateral resolution. The beam width is determined by the choice of source and apodization function, the frequency, and the physics of focusing. Postprocessing strategies to improve lateral resolution can be limited by the need for conditioning the mathematics of inverse filtering, due to instabilities. We present an analysis that defines key constraints on sampled versions of lateral beampatterns. Within these constraints are useful symmetric beampatterns, which, when properly sampled, can have a stable inverse filter. A framework for analysis and processing is described and applied to phantoms and tissues to demonstrate the improvements that can be realized. PMID- 27403447 TI - Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. AB - Cerebral blood flow (CBF) and cerebral autoregulation (CA) are critically important to maintain proper brain perfusion and supply the brain with the necessary oxygen and energy substrates. Adequate brain perfusion is required to support normal brain function, to achieve successful aging, and to navigate acute and chronic medical conditions. We review the general principles of CBF measurements and the current techniques to measure CBF based on direct intravascular measurements, nuclear medicine, X-ray imaging, magnetic resonance imaging, ultrasound techniques, thermal diffusion, and optical methods. We also review techniques for arterial blood pressure measurements as well as theoretical and experimental methods for the assessment of CA, including recent approaches based on optical techniques. The assessment of cerebral perfusion in the clinical practice is also presented. The comprehensive description of principles, methods, and clinical requirements of CBF and CA measurements highlights the potentially important role that noninvasive optical methods can play in the assessment of neurovascular health. In fact, optical techniques have the ability to provide a noninvasive, quantitative, and continuous monitor of CBF and autoregulation. PMID- 27403450 TI - Three challenges for connecting model to mechanism in decision-making. AB - Recent years have seen a growing interest in understanding the neural mechanisms that support decision-making. The advent of new tools for measuring and manipulating neurons, alongside the inclusion of multiple new animal models and sensory systems has led to the generation of many novel datasets. The potential for these new approaches to constrain decision-making models is unprecedented. Here, we argue that to fully leverage these new approaches, three challenges must be met. First, experimenters must design well-controlled behavioral experiments that make it possible to distinguish competing behavioral strategies. Second, analyses of neural responses should think beyond single neurons, taking into account tradeoffs of single-trial versus trial-averaged approaches. Finally, quantitative model comparisons should be used, but must consider common obstacles. PMID- 27403451 TI - Identification of Genes Coding Aminoglycoside Modifying Enzymes in E. coli of UTI Patients in India. AB - This study is to probe the pattern of antibiotic resistance against aminoglycosides and its mechanism in E. coli obtained from patients from Chennai, India. Isolation and identification of pathogens were done on MacConkey agar. Antimicrobial sensitivity testing was done by disc diffusion test. The identification of genes encoding aminoglycoside modifying enzymes was done by Polymerase Chain Reaction (PCR). Out of 98 isolates, 71 (72.45%) isolates were identified as E. coli and the remaining 27 (27.55%) as other bacteria. Disc diffusion method results showed a resistance level of 72.15% for streptomycin, 73.4% for gentamicin, 63.26% for neomycin, 57.14% for tobramycin, 47.9% for netilmicin, and 8.16% for amikacin in E. coli. PCR screening showed the presence of four genes, namely, rrs, aacC2, aacA-aphD, and aphA3, in their plasmid DNA. The results point towards the novel mechanism of drug resistance in E. coli from UTI patients in India as they confirm the presence of genes encoding enzymes that cause resistance to aminoglycoside drugs. This could be an alarm for drug prescription to UTI patients. PMID- 27403453 TI - Knowledge and Attitude of Obstetric Care Providers on Partograph and Its Associated Factors in East Gojjam Zone, Northwest Ethiopia. AB - Introduction. Universal use of partograph is recommended during labor, to improve maternal and fetal outcome. The aim was to assess knowledge and attitude of obstetric caregivers about partograph and associated factors. Methods. Facility based cross-sectional study was conducted on 273 study participants. Study facilities and study units were selected using simple random sampling technique. Midwives, Nurses, Public Health Officers, Medical Doctors, and masters in Emergency Surgery and Obstetric were included in the study. Epi-data and SPSS statistical software were used. Results. About 153 (56.04%) and 150 (54.95%) of the obstetric caregivers had good knowledge and favorable attitude about partograph, respectively. Knowledge of partograph was significantly higher among obstetric caregivers that learnt about partograph during their College and who had received partograph on job training (AOR: 2.14, 95% C.I (1.17-3.93)) and (AOR: 2.25, 95% C.I (1.21-4.19)), respectively. Favorable attitude towards partograph was significantly higher among obstetrical caregivers who had training and learnt about partograph during their college (AOR: 3.37, 95% C.I (1.49-5.65)) and (AOR: 2.134, 95% C.I (1.175-3.877)), correspondingly. Conclusion. Above half of obstetric caregivers had good knowledge and a favorable attitude on partograph. The provision of on preservice and job training is necessary to improve caregivers' knowledge and attitude. PMID- 27403452 TI - Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis. AB - Nucleotide-binding oligomerization domain-containing protein (Nod) 2 is an intracellular pattern recognition receptor, which recognizes muramyl dipeptide (N Acetylmuramyl-L-Alanyl-D-Isoglutamine: MDP), a bacterial peptidoglycan component, and makes a NF-kappaB-activating complex called nodosome with adaptor protein RICK (RIP2/RIPK2). Nod2 mutants are associated with the autoinflammatory diseases, Blau syndrome (BS)/early-onset sarcoidosis (EOS). For drug discovery of BS/EOS, we tried to develop Nod2-nodosome in a cell-free system. FLAG-tagged RICK, biotinylated-Nod2, and BS/EOS-associated Nod2 mutants were synthesized, and proximity signals between FLAG-tagged and biotinylated proteins were detected by amplified luminescent proximity homogeneous assay (ALPHA). Upon incubation with MDP, the ALPHA signal of interaction between Nod2-WT and RICK was increased in a dose-dependent manner. The ALPHA signal of interaction between RICK and the BS/EOS-associated Nod2 mutants was more significantly increased than Nod2-WT. Notably, the ALPHA signal between Nod2-WT and RICK was increased upon incubation with MDP, but not when incubated with the same concentrations, L-alanine, D isoglutamic acid, or the MDP-D-isoform. Thus, we successfully developed Nod2 nodosome in a cell-free system reflecting its function in vivo, and it can be useful for screening Nod2-nodosome-targeted therapeutic molecules for BS/EOS and granulomatous inflammatory diseases. PMID- 27403454 TI - Comparison of Muscle Onset Activation Sequences between a Golf or Tennis Swing and Common Training Exercises Using Surface Electromyography: A Pilot Study. AB - Aim. The purpose of this pilot study is to use surface electromyography to determine an individual athlete's typical muscle onset activation sequence when performing a golf or tennis forward swing and to use the method to assess to what degree the sequence is reproduced with common conditioning exercises and a machine designed for this purpose. Methods. Data for 18 healthy male subjects were collected for 15 muscles of the trunk and lower extremities. Data were filtered and processed to determine the average onset of muscle activation for each motion. A Spearman correlation estimated congruence of activation order between the swing and each exercise. Correlations of each group were pooled with 95% confidence intervals using a random effects meta-analytic strategy. Results. The averaged sequences differed among each athlete tested, but pooled correlations demonstrated a positive association between each exercise and the participants' natural muscle onset activation sequence. Conclusion. The selected training exercises and Turning PointTM device all partially reproduced our athletes' averaged muscle onset activation sequences for both sports. The results support consideration of a larger, adequately powered study using this method to quantify to what degree each of the selected exercises is appropriate for use in both golf and tennis. PMID- 27403455 TI - Goniometry and Limb Girth in Miniature Dachshunds. AB - Purpose. To report the mean and median pelvic limb joint angles and girth measurements in miniature Dachshunds presenting with varying degrees of pelvic limb weakness secondary to thoracolumbar intervertebral disc extrusion. Methods. 15 miniature Dachshunds who presented to WSU-VTH for thoracolumbar disc extrusion. Dachshunds varied in neurologic status from ambulatory paraparetic to paraplegic at the time of measurements. Results. There were no significant differences in joint angles or girth among the three groups (ambulatory paraparetic, nonambulatory paraparetic, or paraplegic) (P > 0.05). When group was disregarded and values for extension, flexion, and girth combined, no differences existed. Conclusions. Goniometry and limb girth measurements can successfully be made in the miniature Dachshund; however, the shape of the Dachshund leg makes obtaining these values challenging. There were no differences in joint angle or girth measurements between dogs with varying neurologic dysfunction at the time of measurement. PMID- 27403456 TI - Risky Sexual Behaviors and Associated Factors among Jiga High School and Preparatory School Students, Amhara Region, Ethiopia. AB - Background. Young people constitute a large number of population worldwide, and majority of this population group lives in developing countries. They are at high risk of engaging in risky sexual behaviors. These risk sexual behaviors predispose youths to several sexual and reproductive health problems like STIs, HIV, unwanted pregnancy, and abortion. So, this study was conducted to assess the magnitude of risky sexual behaviors and associated factors among Jiga high school and preparatory school students, northwest Ethiopia. Methodology. Institutional based cross-sectional study design was conducted among Jiga town high school and preparatory school students. A total of 311 students were included in the study. Systematic random sampling method was used to select study participants. Data was entered using EpiData version 3.1 and it was exported to SPSS version 22 for further analysis. Descriptive analysis and bivariate and multivariate analysis were also calculated to determine factors associated with risky sexual behavior. Result. Forty-eight (16%) of respondents reported that they had sexual intercourse. From those who start sex, 44 (14.7%) were involved in risky sexual behavior which could predispose them to sexual and reproductive health problems. More than half, 27 (56.3%), of respondents first sexual intercourse was before their eighteenth birthday. The mean age and SD of fist sexual initiation were 17.2 years old and 1.35 years, respectively. Factors associated with risky sexual behavior include respondents between the ages of 20 and 23 (AOR: 5, 95%, CI: 1.59 15.98), drinking alcohol (AOR: 2.48, 95% CI: 1.13-5.41), and having poor knowledge towards HIV/AIDS (AOR: 4.53, 95%, CI: 2.06-9.94). Conclusion. A large number of in-school youths are involved in risky sexual behaviors like early sexual initiation, having multiple sexual partners, inconsistence use of condom, and having sex with high risk partner (CSWs). Age of respondents, alcohol drinking, and poor knowledge towards HIV/AIDS were factors associated with risky sexual behavior. School and community based programs in reducing substance abuse among youths and increasing their knowledge towards HIV/AIDS are important. PMID- 27403457 TI - Ants Can Expect the Time of an Event on Basis of Previous Experiences. AB - Working on three ant species of the genus Myrmica, M. ruginodis, M. rubra, and M. sabuleti, we showed that foragers can expect the subsequent time at which food will be available on the basis of the previous times at which food was present. The ants acquired this expectative ability right after having experienced two time shifts of food delivery. Moreover, the ants' learning score appeared to be a logarithmic function of time (i.e., of the number of training days). This ability to expect subsequent times at which an event will occur may be an advantageous ethological trait. PMID- 27403459 TI - Translation, Adaptation and Initial Validation of Food Allergy Quality of Life Questionnaire: Child form in Greek. AB - The aim of the study is to determine the reliability and validity of the Greek version of the Food Allergy Quality of life Questionnaire-Child Form (FAQLQ-CF). After linguistic validation, the Greek FAQLQ-CF, Food Allergy Independent Measure (FAIM) and Pediatric Quality of Life Inventory (PedsQLTM) were used by a physician to interview children diagnosed with food allergy and aged 8-12 via telephone. Cronbach's alpha was used to evaluate reliability, and factor analysis to assess construct validity. The correlation between FAQLQ-CF and FAIM was moderate (rho=0.509, P<0.001) and internal consistency was strong (Cronbach's alpha 0.905). FAQLQ-CF discriminated well each question's contribution to children's quality of life deterioration (32-80%), each child's quality of life (17-89%), children differing in doing things with others (total score 3.55 vs 2.57, difference =0.98 > minimal clinical importance difference = 0.5; P<0.001), but not children differing in reporting anaphylaxis. The total FAQLQ-CF score correlated with the total PedsQLTM score and with the score of one of PedsQLTM subscales, demonstrating convergent validity. Factor analysis uncovered an underlying structure of four factors, explaining 50% of the variance. We can conclude that Greek FAQLQ-CF is a reliable, valid, discriminant tool for interviewing food allergic children aged 8-12, detecting those in need for immediate care. PMID- 27403458 TI - Caries Risk Assessment Item Importance: Risk Designation and Caries Status in Children under Age 6. AB - BACKGROUND: Caries risk assessment (CRA) is widely recommended for dental caries management. Little is known regarding how practitioners use individual CRA items to determine risk and which individual items independently predict clinical outcomes in children under age 6-years. OBJECTIVES: Assess the relative importance of pediatric CRA items in dental providers' decision-making regarding patient risk and in association with clinically evident caries, cross-sectionally and longitudinally. METHODS: CRA information was abstracted retrospectively from electronic patient records of children initially ages 6-72 months at a university pediatric dentistry clinic (N=3810 baseline; N=1315 with follow-up). The 17-item CRA form included caries risk indicators, caries protective items, and clinical indicators. Conditional random forests classification trees were implemented to identify and assign variable importance to CRA items independently associated with baseline high-risk designation, baseline evident tooth decay, and follow-up evident decay. RESULTS: Thirteen individual CRA items, including all clinical indicators and all but one risk indicator, were independently and statistically significantly associated with student/resident providers' caries-risk designation. Provider-assigned baseline risk category was strongly associated with follow-up decay, which increased from low (20.4%), moderate (30.6%), to high/extreme risk patients (68.7%). Of baseline CRA items, before adjustment 12 were associated with baseline decay and 7 with decay at follow-up; however, in the conditional random forests models, only the clinical indicators (evident decay, dental plaque, and recent restoration placement) and one risk indicator (frequent snacking) were independently and statistically significantly associated with future disease, for which baseline evident decay was the strongest predictor. CONCLUSIONS: In this predominantly high-risk population under caries preventive care, more individual CRA items were independently associated with providers' risk determination than with future caries status. These university dental providers considered many items in decision-making regarding patient risk, suggesting that in turn, these comprehensive CRA forms could also aid individualized care, linking risk assessment to disease management. PMID- 27403460 TI - An Exploratory Study on the Information Needs of Prostate Cancer Patients and Their Partners. AB - The aim of this study is to explore the information needs of men with prostate cancer and their partners retrospectively at various points in the treatment process. An online questionnaire was used to collect information from men with prostate cancer and their partners about information needs, and when these developed. Readers of a Prostate Care Cookbook and members of a Prostate Cancer Charity were invited to participate: 73 men with prostate cancer and 25 partners completed the questionnaire. Responses showed that participants develop their information needs close to diagnosis. Less educated men with prostate cancer and partners developed their needs closer to the time after diagnosis than those with higher education. Partners develop an interest on information related to treatment and interaction earlier than patients. Patients prioritised treatment and disease-specific information. Patients and partners differ in how their information needs develop. Medical information is prioritized by patients as opposed to practical information by partners. Health care provision can be tailored to meet the different needs of prostate cancer patients and their partners at different times in the treatment process. PMID- 27403461 TI - Being a Victim of Medical Error in Brazil: An (Un)Real Dilemma. AB - Medical error stems from inadequate professional conduct that is capable of producing harm to life or exacerbating the health of another, whether through act or omission. This situation has become increasingly common in Brazil and worldwide. In this study, the aim was to understand what being the victim of medical error is like and to investigate the circumstances imposed on this condition of victims in Brazil. A semi-structured interview was conducted with twelve people who had gone through situations of medical error in their lives, creating a space for narratives of their experiences and deep reflection on the phenomenon. The concept of medical error has a negative connotation, often being associated with the incompetence of a medical professional. Medical error in Brazil is demonstrated by low-quality professional performance and represents the current reality of the country because of the common lack of respect and consideration for patients. Victims often remark on their loss of identity, as their social functions have been interrupted and they do not expect to regain such. It was found, however, little assumption of error in the involved doctors' discourses and attitudes, which felt a need to judge the medical conduct in an attempt to assert their rights. Medical error in Brazil presents a punitive character and is little discussed in medical and scientific circles. The stigma of medical error is closely connected to the value and cultural judgments of the country, making it difficult to accept, both by victims and professionals. PMID- 27403462 TI - Mood Changes After Indoor Tanning Among College Women: Associations with Psychiatric/Addictive Symptoms. AB - Indoor tanning (IT) has been linked with psychiatric and addictive symptoms, and frequent tanning may indicate tanning dependence (addiction). The current study evaluated the effects of an IT episode on mood states and the association of these effects with psychiatric and addictive symptoms among young adult female indoor tanners. One-hundred thirty-nine female university students aged 18-25 years who had indoor tanned completed an online survey including the Positive and Negative Affects Scales and a standardized psychiatric interview (the MINI International Neuropsychiatric Interview) via telephone. Psychiatric and addictive symptoms were relatively common among these young adult female indoor tanners. Overall, participants reported significant decreases in both negative (upset, scared, irritable, nervous, jittery, afraid) and positive (feeling interested) mood states after their most recent tanning episode. Multivariable linear regression analyses showed that more frequent indoor tanning in the past month and symptoms of illicit drug use disorders were associated with decreases in negative mood, and symptoms of generalized anxiety disorder were associated with a decrease in feeling interested. In summary, indoor tanners report relatively high rates of psychiatric and substance use symptoms, including symptoms of tanning dependence, and indoor tanning appears to alter mood. Women with certain substance use and psychiatric characteristics may be more vulnerable to such mood changes after tanning indoors. Further research is needed to clarify the relationships among these variables. PMID- 27403463 TI - The Impact of Socioeconomic Conditions, Social Networks, and Health on Frail Older People's Life Satisfaction: A Cross-Sectional Study. AB - It has been shown that frailty is associated with low levels of well-being and life satisfaction. Further exploration is needed, however, to better understand which components constitute life satisfaction for frail older people and how satisfaction is related to other life circumstances. The aim of this study was to examine relationships between frail older people's life satisfaction and their socioeconomic conditions, social networks, and health-related conditions. A cross sectional study was conducted (n=179). A logistic regression analysis was performed, including life satisfaction as the dependent variable and 12 items as independent variables. Four of the independent variables made statistically significant contributions: financial situation (OR 3.53), social contacts (OR 2.44), risk of depression (OR 2.26), and self-rated health (OR 2.79). This study demonstrates that financial situation, self-rated health conditions and social networks are important components for frail older people's life satisfaction. Health and social care professionals and policy makers should consider this knowledge in the care and service for frail older people; and actions that benefit life satisfaction - such as social support - should be promoted. PMID- 27403467 TI - Preface. PMID- 27403464 TI - The Effectiveness of Health Literacy Oriented Programs on Physical Activity Behaviour in Middle Aged and Older Adults with Type 2 Diabetes: A Systematic Review. AB - Health literacy is the first step to self-management of type II diabetes mellitus, of which physical activity is the least compliant behavior. However, no reviews have summarized the effect and the process of interventions of health literacy oriented programs on physical activity behavior among middle aged and older adults with type II diabetes mellitus. This article is the first to examine the effectiveness of health literacy oriented programs on physical activity behavior among middle aged and older adults with type II diabetes mellitus. This systematic review extracted articles from nine electronic databases between 1990 and 2013. Six interventional studies were extracted and reported in accordance with the guidance of Preferred Reporting Items for Systematic Reviews and Meta Analyses. Findings demonstrated that health literacy oriented programs increased the frequency and duration of physical activity among patients with high health literacy. Although some studies effectively improved the health literacy of physical activity, gap in literature remains open for the indistinct and unreliable measurement of physical activity within self-management programs of type II diabetes mellitus, and the questionable cross-culture generalizability of findings. Further studies with well-knit theory-based intervention with respect to patients' cultural background, duration of intervention and objective measurements are encouraged to elucidate the relationship between health literacy oriented programs and physical activity behavior. PMID- 27403468 TI - Preface. PMID- 27403469 TI - [Complication of a bilateral ileal ureteral replacement]. PMID- 27403470 TI - International Profile. PMID- 27403471 TI - [Nutcracker syndrome]. PMID- 27403472 TI - Visual Computing and the Progress of Developing Countries. PMID- 27403473 TI - Guest Editorial: Special Section on CVPR 2013. PMID- 27403474 TI - Measuring quality-of-care in the context of sustainable development goal 3: a call for papers. PMID- 27403475 TI - Editorial comment. PMID- 27403476 TI - Author reply. PMID- 27403477 TI - Never in a month of Sundays. PMID- 27403478 TI - [Not Available]. PMID- 27403479 TI - [Not Availabe]. PMID- 27403480 TI - [Not Available]. PMID- 27403481 TI - [Not Available]. PMID- 27403482 TI - [Not Available]. PMID- 27403513 TI - Local Affinity Release. AB - The use of hydrogels for therapeutic delivery is a burgeoning area of investigation. These water-swollen polymer matrices are ideal platforms for localized drug delivery that can be further combined with specific ligands or nanotechnologies to advance the controlled release of small-molecule drugs and proteins. Due to the advantage of hydrophobic, electrostatic, or specific extracellular matrix interactions, affinity-based strategies can overcome burst release and challenges associated with encapsulation. Future studies will provide innovative binding tools, truly stimuli-responsive systems, and original combinations of emerging technologies to control the release of therapeutics spatially and temporally. Local drug delivery can be achieved by directly injecting a therapeutic to its site of action and is advantageous because off target effects associated with systemic delivery can be minimized. For prolonged benefit, a vehicle that provides sustained drug release is required. Hydrogels are versatile platforms for localized drug release, owing to the large library of biocompatible building blocks from which they can be formed. Injectable hydrogel formulations that gel quickly in situ and provide sustained release of therapeutics are particularly advantageous to minimize invasiveness. The incorporation of polymers, ligands or nanoparticles that have an affinity for the therapeutic of interest improve control over the release of small-molecule drugs and proteins from hydrogels, enabling spatial and temporal control over the delivery. Such affinity-based strategies can overcome drug burst release and challenges associated with protein instability, allowing more effective therapeutic molecule delivery for a range of applications from therapeutic contact lenses to ischemic tissue regeneration. PMID- 27403514 TI - [Orthopedic Associations in Mexico]. AB - No Abstract available. PMID- 27403515 TI - [Comparative study of the repair of full thickness tear of the supraspinatus by means of "single row" or "suture bridge" techniques]. AB - PURPOSE: The purpose of this study is to analyze if there is any difference between the arthroscopic reparation of full-thickness supraspinatus tears with simple row technique versus suture bridge technique. MATERIAL AND METHODS: We accomplished a retrospective study of 123 patients with full-thickness supraspinatus tears between January 2009 and January 2013 in our hospital. There were 60 simple row reparations, and 63 suture bridge ones. RESULTS: The mean age in the simple row group was 62.9, and in the suture bridge group was 63.3 years old. There were more women than men in both groups (67%). All patients were studied using the Constant test. The mean Constant test in the suture bridge group was 76.7, and in the simple row group was 72.4. We have also accomplished a statistical analysis of each Constant item. Strength was higher in the suture bridge group, with a significant statistical difference (p 0.04). The range of movement was also greater in the suture bridge group, but was not statistically significant. CONCLUSIONS: Suture bridge technique has better clinical results than single row reparations, but the difference is not statistically significant (p = 0.298). PMID- 27403516 TI - [Prevalence and clinicopathological characteristics of giant cell tumors]. AB - The frequency of giant cell tumors reported in the literature is very variable. Considering that our population has its own features, which distinguish it from the Anglo-Saxon and Asian populations, we think that both the frequency and the clinical characteristics of giant cell tumors in our population are different. The major aim of this paper was to determine the frequency and clinicopathological characteristics of giant cell tumors of the bone. A cross sectional descriptive study was conducted of the cases diagnosed at our service as giant cell tumors of the bone from January to December 2013. The electronic clinical records, radiologic records and histologic slides from each case were reviewed. Giant cell tumors represented 17% of total bone tumors and 28% of benign tumors. Patients included 13 females and 18 males. The most frequent locations of giant cell tumors were: the proximal tibia, 9 cases (29%), and the distal femur, 6 cases (19%). Forty-five percent of giant cell tumors were associated with aneurysmal bone cyst (ABC) (14 cases) and one case (3%) was malignant. The frequency of giant cell tumors in this case series was intermediate, that is, higher than the one reported in Anglo-Saxon countries (usually low), but without reaching the frequency rates reported in Asian countries (high). PMID- 27403517 TI - [Classification of pediatric supracondylar fractures: Gartland, AO and Holmberg: Which has the best interobserver agreement?]. AB - METHODS: Several classifications have been proposed for supracondylar fractures of the humerus. The purpose of this study was to assess the reproducibility and interobserver agreement of the Holmbert, Gartland and AO classifications. Retrospective study consisting of concurrent, blind and independent assessments of a consecutive sample of 42 elbow X-rays (AP and lateral) of pediatric patients with supracondylar fractures. Three observers, with similar degree of training, evaluated the X-rays independently and scored each one of them using the 3 scales compared herein. The interobserver agreement was assessed using Kendalls Tau-b ratio; the arithmetic mean was calculated and the ratios were compared with Fishers transformation. The interpretation was made using the standards proposed by Landis Koch. RESULTS: The Holmberg and Gartland classifications had a mean correlation coefficient of 0.654 and 0.706, respectively (p 0.001). Holmbergs classification provides a better anatomical description. The mean correlation coefficient of the AO classification was 0.491 (p = 0.001).The difference between the correlation coefficients was 0.052 for Holmbert/Gartland; 0.163 for Holmberg/AO, and 0.215 for Gartland/AO. There were no statistically significant differences among these values, but there were epistemological differences. According to Landis and Koch, the Holmberg and Gartland classifications show a substantial agreement, while the AO classification showed a moder ate agreement. CONCLUSION: Holmbergs classification is the most recommendable one. PMID- 27403518 TI - Changes in the radiological measurements of the tibiofibular syndesmal area in patients with Weber C ankle fractures who were treated with open reduction, internal fixation, and transyndesmal screw. AB - The tibiofibular syndesmosis provides stability to the ankle mortise. The ankle syndesmosis is compromised in all Weber C type injuries. The radiographic method described by Merle DAubigne considers the bony relationships as a measure of syndesmotic widening. We sought to investigate whether the patients with a C type ankle fracture treated with ORIF and placement of a transyndesmal screw have an increment of the tibiofibular space and decrease of the tibiofibular overlap after the transyndesmal screw is removed. Our sample included 52 patients with Weber C ankle fractures treated by ORIF and transyndesmal screw at a level II trauma center. We measured the tibiofibular clear space and tibiofibular overlap in each phase of the treatment. The transyndesmal screw was removed at day 55.56 (+/- 21.83). We found an increase of the tibiofibular overlap of 0.20 mm (+/- 2.29, p = 0.532); and 0.21 mm (+/- 0.97, p = 0.146) in the tibiofibular clear space. The changes of 2.38% in the tibiofibular overlap and 5.29% in the tibiofibular clear space between the postoperative and post-removal periods were not statistically significant. After removal of the syndesmal screw, there is a slight radiographic broadening of the syndesmosis; however, it is small and statistically not significant. PMID- 27403519 TI - [Using a new implant: U-Force N6 to level L5 S1 to avoid lumbar instability after single discectomy]. AB - INTRODUCTION: We conducted a retrospective study in patients with disc herniation and compared the results obtained in individuals treated with the U device N6 with those acquired in patients treated without any device. The U device is a titanium alloy implant that is placed between the spinous processes. MATERIAL AND METHODS: In a cohort of 50 patients with degenerative lumbar disc, 25 underwent surgical treatment in which the U device was placed and 25 control individuals were treated with discectomy alone. Patients underwent serial follow-up evaluations, and radiographic assessment was used to determine the outcome. Up to two years of follow-up data were obtained in all patients (2013-2014). RESULTS: Statistically significant improvement was seen in patients treated with the coflex device in the management of lumbar disc degeneration to avoid lumbar instability in the future (p 0.01). It allowed its placement in 90% of the patients. CONCLUSIONS: Our study shows that the coflex device was more effective than the discectomy group in the management of lumbar instability. Ninety percent of the cases of the N6 group present the device at L5 S1 versus 60% of the historical group with other devices (2004-2011). PMID- 27403520 TI - [Inveterate radio-humeral dislocation in children. Case report and literature review]. AB - INTRODUCTION: Radio-humeral dislocation is rare, as it generally occurs with ulnar fracture. It is unusual in children and chronic lesions are even more unusual. OBJECTIVE: Report of a case, its treatment and two-year follow-up. MATERIAL AND METHOD: Treatment consisted of open reduction and annular ligamentoplasty with fascia lata allograft, maintaining the reduction with a Kirschner nail for 6 weeks. The latter was then removed and rehabilitation was started. RESULT: The two-year follow-up report stated that the child has resumed his activities at school and his physical activity. DISCUSSION: The authors report that the techniques used to approach inveterate lesions should include shortening the ulna to be able to reduce the radius and maintain it. The standard technique was modified and good results were obtained. PMID- 27403521 TI - [Dome shaped osteotomy combined with transposition of the ulnar nerve as a treatment for post-traumatic ulnar valgus in a pediatric patient]. AB - A sequel of supracondylar fractures of distal humerus in children is the angular deformity. It is usually more frequent cubitus varus, but there are reported cases of cubitus valgus. The latter may be the cause of the occurrence of a late ulnar nerve neuropathy, which will require treatment. There is controversy as to whether it is possible to successfully treat both problems at the same surgical procedure. This article describes the case of a girl of 11 years old, who has a cubitus valgus deformity secondary to supracondylar fracture of distal humerus of right elbow at the age of seven years, associated with progressive symptoms of ulnar nerve neuropathy. This patient was treated successfully by a single procedure for corrective dome-shaped supracondilar osteotomy associated with subcutaneous anterior transposition of the ulnar nerve through a posterior approach. PMID- 27403522 TI - [Closed reduction of the sacroiliac joint and acetabular reconstruction in a pediatric patient with a Torode/Zieg IVd unstable pelvic fracture. Case report]. AB - BACKGROUND: High-energy severe pelvic injuries in pediatric patients are rare, particularly those associated with acetabular fractures. They are life threatening injuries. METHOD: We report the case of a pediatric patient with a diagnosis of a Torode/Zieg IVd pelvic fracture. The clinical and radiographic data was reviewed retrospectively. CLINICAL CASE: Male, 12 year-old polytraumatized patient with an unstable pelvic fracture who underwent multidisciplinary treatment. He was stabilized in the intensive care unit; the general surgery service performed laparotomy; orthopedic management consisted of closed reduction and internal fixation of the sacroiliac fracture-dislocation and later of open reduction and internal fixation of the right acetabular fracture. The patient's clinical course was appropriate. CONCLUSIONS: A diagnosis of a type IVd Torode/Zieg fracture is an absolute indication for surgical management. A multidisciplinary approach is essential to save the life of patients with unstable pelvic lesions. This case shows the complexity of an unstable pelvic fracture associated with multiple injuries, due to a rather infrequent mechanism of injury (being crushed by a tree) in a patient with an immature skeletal system. PMID- 27403525 TI - Resting Energy Expenditure of Black Overweight Women in South Africa Is Lower than of White Women. AB - BACKGROUND: Overweight affects 65% of black South African women. Effective weight management requires accurate measurement or estimation of energy expenditure. AIMS: The study aimed to determine, among overweight women, whether measured resting energy expenditure (REE) differs between black and white participants, and the performance of REE estimation equations. METHODS: The REE of 44 black (age 39.6 +/- 9.7 years, body mass index (BMI) 35.1 +/- 6.2 kg/m2) and 41 white (age 38.0 +/- 11.6 years, BMI 33.9 +/- 7.6 kg/m2) women was measured with indirect calorimetry and estimated with equations. Body composition was assessed with multi-frequency bioelectrical impedance analysis. Differences in REE were determined with t tests (Welch), and included adjustment for fat free mass (FFM) and BMI, and for FFM index (FFMI). RESULTS: Measured REE was 585 kJ/day (95% CI 264-905; p = 0.0005) and 861 kJ/day (95% CI 499-1,221; p < 0.0001) lower in black than in white women when adjusted for FFM and BMI, and FFMI, respectively. Out of 14 equations, 13 underestimated REE (error range 2,261 +/- 727 kJ/day (Bernstein equation, white women) to 8 +/- 782 kJ/day (BMI equation, black women)). CONCLUSIONS: Black overweight women have significantly lower REE than their white counterparts. No tested estimation equation provided satisfactory results across race/ethnicity. REE measurements or development of overweight- or race/ethnicity specific estimation equations are recommended. PMID- 27403523 TI - Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens. AB - Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection. PMID- 27403524 TI - Dermal gammadelta T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns. AB - BACKGROUND: Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident gammadelta T-cells that reside in skin. METHODS: Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal gammadelta T cells were incubated with MTDs (0-500 MUg/ml) for 24 hr and cells and supernatants were collected for analysis. RESULTS: MTDs activated dermal gammadelta T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL 1beta, IL-6), and growth factors (PDGF and VEGF) by gammadelta T-cells. CONCLUSIONS: These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal gammadelta T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes. PMID- 27403526 TI - Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel. AB - General anesthetics bind reversibly to ion channels, modifying their global conformational distributions, but the underlying atomic mechanisms are not completely known. We examine this issue by way of the model protein Gloeobacter violaceous ligand-gated ion channel (GLIC) using computational molecular dynamics, with a coarse-grained model to enhance sampling. We find that in flooding simulations, both propofol and a generic particle localize to the crystallographic transmembrane anesthetic binding region, and that propofol also localizes to an extracellular region shared with the crystallographic ketamine binding site. Subsequent simulations to probe these binding modes in greater detail demonstrate that ligand binding induces structural asymmetry in GLIC. Consequently, we employ residue interaction correlation analysis to describe the internal allosteric network underlying the coupling of ligand and distant effector sites necessary for conformational change. Overall, the results suggest that the same allosteric network may underlie the actions of various anesthetics, regardless of binding site. PMID- 27403527 TI - Establishing a Wild, Ex Situ Population of a Critically Endangered Shade-Tolerant Rainforest Conifer: A Translocation Experiment. AB - Translocation can reduce extinction risk by increasing population size and geographic range, and is increasingly being used in the management of rare and threatened plant species. A critical determinant of successful plant establishment is light environment. Wollemia nobilis (Wollemi pine) is a critically endangered conifer, with a wild population of 83 mature trees and a highly restricted distribution of less than 10 km2. We used under-planting to establish a population of W. nobilis in a new rainforest site. Because its optimal establishment conditions were unknown, we conducted an experimental translocation, planting in a range of different light conditions from deeply shaded to high light gaps. Two years after the experimental translocation, 85% of plants had survived. There were two distinct responses: very high survival (94%) but very low growth, and lower survival (69%) and higher growth, associated with initial plant condition. Overall survival of translocated W. nobilis was strongly increased in planting sites with higher light, in contrast to previous studies demonstrating long-term survival of wild W. nobilis juveniles in deep shade. Translocation by under-planting may be useful in establishing new populations of shade-tolerant plant species, not least by utilizing the range of light conditions that occur in forest understories. PMID- 27403528 TI - Correction: Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients. AB - [This corrects the article DOI: 10.1371/journal.pone.0150900.]. PMID- 27403529 TI - What Medical Oncologist Residents Think about the Italian Speciality Schools: A Survey of the Italian Association of Medical Oncology (AIOM) on Educational, Clinical and Research Activities. AB - BACKGROUND AND OBJECTIVES: Relevant heterogeneity exists among Postgraduate Schools in Medical Oncology, also within the same country. In order to provide a comprehensive overview of the landscape of Italian Postgraduate Schools in Medical Oncology, the Italian Association of Medical Oncology (AIOM) undertook an online survey, inviting all the residents to describe their daily activities and to express their overall satisfaction about their programs. METHODS: A team composed of five residents and three consultants in medical oncology prepared a 38 items questionnaire that was published online in a reserved section, accessible through a link sent by e-mail. Residents were invited to anonymously fill in the questionnaire that included the following sub-sections: quality of teaching, clinical and research activity, overall satisfaction. RESULTS: Three hundred and eleven (57%) out of 547 invited residents filled in the questionnaire. Two-hundred and twenty-three (72%) participants declared that attending lessons was frequently difficult and 153 (49%) declared they did not gain substantial improvement in their knowledge from them. Fifty-five percent stated that they did not receive lessons on palliative care. Their overall judgment about didactic activity was low in 63% of the interviewed. The satisfaction for clinical activity was in 86% of cases good: 84% recognized that, during the training period, they acquired a progressive independence on patients' management. About research activity, the majority (79%) of participants in the survey was actively engaged in managing patients included in clinical trials but the satisfaction level for the involvement in research activities was quite low (54%). Overall, 246 residents (79%) gave a positive global judgment of their Medical Oncology Schools. CONCLUSIONS: The landscape of Italian Postgraduate Schools in Medical Oncology is quite heterogeneous across the country. Some improvements in the organization of teaching and in the access to research opportunity are needed; the perception about clinical activity and the overall judgment of the programs are quite satisfactory. PMID- 27403530 TI - Studying the Role of Alveolar Macrophages in Breast Cancer Metastasis. AB - This paper describes the application of the syngeneic model of breast cancer (4T1) to the studies on a role of pulmonary alveolar macrophages in cancer metastasis. The 4T1 cells expressing GFP in combination with imaging and confocal microscopy are used to monitor tumor growth, track metastasizing tumor cells, and quantify the metastatic burden. These approaches are supplemented by digital histopathology that allows the automated and unbiased quantification of metastases. In this method the routinely prepared histological lung sections, which are stained with hematoxylin and eosin, are scanned and converted to the digital slides that are then analyzed by the self-trained pattern recognition software. In addition, we describe the flow cytometry approaches with the use of multiple cell surface markers to identify alveolar macrophages in the lungs. To determine impact of alveolar macrophages on metastases and antitumor immunity these cells are depleted with the clodronate-containing liposomes administrated intranasally to tumor-bearing mice. This approach leads to the specific and efficient depletion of this cell population as confirmed by flow cytometry. Tumor volumes and lung metastases are evaluated in mice depleted of alveolar macrophages, to determine the role of these cells in the metastatic progression of breast cancer. PMID- 27403531 TI - Transcriptomic Profiling of Adipose Tissue in Obese Women in Response to Acupuncture Catgut Embedding Therapy with Moxibustion. AB - OBJECTIVE: Complementary and alternative medicine, such as Traditional Chinese Medicine, represents an efficient therapeutic option for obesity control. It was previously reported that acupuncture catgut embedding therapy (ACET) with moxibustion reduces body weight and reverts insulin resistance in obese women. This study aimed to evidence changes in adipokines and gene expression in adipose tissue that could explain the effects of ACET with moxibustion. DESIGN: Overweight/obese women were treated with ACET with moxibustion or sham acupuncture as control. Peripheral blood samples and fat biopsies were taken before and after intervention. Circulating adipokines (leptin, adiponectin, tumor necrosis factor alpha, and resistin) were quantified by enzyme-linked immunosorbent assay. Gene expression in adipose tissue was determined by cDNA microarray assays and assessed by quantitative reverse transcription real-time polymerase chain reaction. RESULTS: ACET with moxibustion did not modify circulating adipokines levels. However, correlations with anthropometric and biochemical parameters were affected. Interestingly, transcriptional changes in adipose tissue revealed the modulation of genes participating in homeostasis control, lipid metabolism, olfactory transduction, and gamma-aminobutyric acid signaling pathway. CONCLUSIONS: The effects of ACET with moxibustion on body weight and insulin resistance were associated with the regulation of biochemical events that are altered in obesity. PMID- 27403532 TI - Profiling the Membrane and Glycosaminoglycan-Binding Proteomes of Moraxella catarrhalis. AB - Moraxella catarrhalis, a Gram-negative bacterium, is an important respiratory pathogen causing acute otitis media and exacerbations of chronic obstructive pulmonary disease. Adhesion of the pathogen to human epithelial cells is mediated via bacterial membrane adhesin proteins. To identify the surface proteome of Moraxella catarrhalis, we applied different membrane protein extraction methods in combination with different proteomic technologies. Proteins from preparations of outer membrane vesicles and from carbonate extractions were analyzed using either a gel-based nano-HPLC-MS/MS technique or 2D-LC-MS/MS. Furthermore, because glycosaminoglycans (GAGs) play an important role for microbial entry into human cells, the GAG-binding membranome of Moraxella catarrhalis was investigated using a glycan-based pull-down approach. By these means, potential vaccine protein candidates that were previously selected by the ANTIGENome technology were confirmed, but importantly also novel proteins were identified as candidates. PMID- 27403533 TI - An ACC Oxidase Gene Essential for Cucumber Carpel Development. AB - Sex determination in plants gives rise to unisexual flowers that facilitate outcrossing and enhance genetic diversity. In cucumber and melon, ethylene promotes carpel development and arrests stamen development. Five sex determination genes have been identified, including four encoding 1 aminocyclopropane-1-carboxylate (ACC) synthase that catalyzes the rate-limiting step in ethylene biosynthesis, and a transcription factor gene CmWIP1 that corresponds to the Mendelian locus gynoecious in melon and is a negative regulator of femaleness. ACC oxidase (ACO) converts ACC into ethylene; however, it remains elusive which ACO gene in the cucumber genome is critical for sex determination and how CmWIP1 represses development of female flowers. In this study, we discovered that mutation in an ACO gene, CsACO2, confers androecy in cucumber that bears only male flowers. The mutation disrupts the enzymatic activity of CsACO2, resulting in 50% less ethylene emission from shoot tips. CsACO2 was expressed in the carpel primordia and its expression overlapped with that of CsACS11 in female flowers at key stages for sex determination, presumably providing sufficient ethylene required for proper CsACS2 expression. CmACO3, the ortholog of CsACO2, showed a similar expression pattern in the carpel region, suggesting a conserved function of CsACO2/CmACO3. We demonstrated that CsWIP1, the ortholog of CmWIP1, could directly bind the promoter of CsACO2 and repress its expression. Taken together, we propose a presumably conserved regulatory module consisting of WIP1 transcription factor and ACO controls unisexual flower development in cucumber and melon. PMID- 27403534 TI - Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation. AB - Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)gamma agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg(-1) irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg(-1)), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARgamma-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI. PMID- 27403536 TI - Pentraxin-3 levels in graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. AB - Acute and chronic graft-versus-host-diseases (aGVHD and cGVHD, respectively) are serious complications after hematopoietic stem cell transplantation (HSCT), impairing survival and quality of life. Because the underlying pathomechanism of GVHD is still poorly understood, we investigated the novel inflammatory marker Pentraxin-3 (PTX3) for its potential role in acute and chronic GVHD compared with autologous HSCT and healthy individuals. We collected plasma samples from patients undergoing autologous (n = 12) and allogeneic (n = 28) HSCT and from healthy individuals (n = 15) throughout 7 days before and up to 1 year after HSCT. PTX3 levels in patients with aGVHD were significantly higher (36.4 +/- 23.6 ng/mL) than in allogeneic patients without aGVHD (10.4 +/- 4.4 ng/mL, p = 0.0001), autologous controls (11.4 +/- 6.7 ng/mL, p = 0.001), or healthy individuals (1.9 +/- 0.6 ng/mL, p < 0.001). PTX3 levels in patients with cGVHD (13.6 +/- 6.3 ng/mL) were significantly lower than in allogeneic patients without cGVHD (25.1 +/- 13.8 ng/mL, p = 0.04) and higher than in autologous controls (8.9 +/- 7.8 ng/mL, p = 0.07) and healthy individuals (1.9 +/- 0.6 ng/mL, p < 0.001). Severity of aGVHD and cGVHD correlated with PTX3 levels. Rising PTX3 levels after HSCT indicated unfavorable outcome. We show that PTX3 levels correlate with the severity of aGVHD, cGVHD, and-with reservations-survival in patients undergoing allogeneic HSCT. PMID- 27403537 TI - Editor's notes. PMID- 27403535 TI - Effects of GlyT1 inhibition on erythropoiesis and iron homeostasis in rats. AB - Glycine is a key rate-limiting component of heme biosynthesis in erythropoietic cells, where the high intracellular glycine demand is primarily supplied by the glycine transporter 1 (GlyT1). The impact of intracellular glycine restriction after GlyT1 inhibition on hematopoiesis and iron regulation is not well established. We investigated the effects of a potent and selective inhibitor of GlyT1, bitopertin, on erythropoiesis and iron homeostasis in rats. GlyT1 inhibition significantly affected erythroid heme biosynthesis, manifesting as microcytic hypochromic regenerative anemia with a 20% steady-state reduction in hemoglobin. Reduced erythropoietic iron utilization was characterized by down regulation of the transferrin receptor 1 (TfR1) on reticulocytes and modest increased iron storage in the spleen. Hepatic hepcidin expression was not affected. However, under the condition of reduced heme biosynthesis with reduced iron reutilization and increased storage iron, hepcidin at the lower and higher range of normal showed a striking role in tissue distribution of iron. Rapid formation of iron-positive inclusion bodies (IBs) was observed in circulating reticulocytes, with an ultrastructure of iron-containing polymorphic mitochondrial remnants. IB or mitochondrial iron accumulation was absent in bone marrow erythroblasts. In conclusion, GlyT1 inhibition in rats induced a steady state microcytic hypochromic regenerative anemia and a species-specific accumulation of uncommitted mitochondrial iron in reticulocytes. Importantly, this glycine-restricted anemia provides no feedback signal for increased systemic iron acquisition and the effects reported are pathogenetically distinct from systemic iron-overload anemias and erythropoietic disorders such as acquired sideroblastic anemia. PMID- 27403538 TI - Coming in sportsmedicine. PMID- 27403540 TI - Scanning Sports. PMID- 27403541 TI - Running wild. PMID- 27403543 TI - Sportsmedicine forum. AB - A Forum for Our Readers Sportsmedicine Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Sportsmedicine Forum, The Physician and Sportsmedicine, 4530 W 77th St, Minneapolis, MN 55435. PMID- 27403547 TI - Noteworthy. PMID- 27403545 TI - Guest editorial. PMID- 27403548 TI - A National Survey of Preparticipation Physical Examination Requirements. AB - In brief: A mail survey of the 50 states and the District of Columbia was conducted to assess the requirements for scholastic preparticipation physical examinations (PPEs). Forty-five replies were received. The results showed that 35 states require a yearly examination and 36 states provide an official state form. Twenty-five states have a medical history questionnaire, but only three states supply a list of contraindications for participation. Several states allow examination by someone other than a physician. Only one of the forms contains a statement of the purpose and/or limitations of the PPE. The requirements and intent of the PPE differ considerably from state to state, indicating that national guidelines for PPEs are needed. PMID- 27403549 TI - Resistance Training: Physiological Responses and Adaptations (Part 3 of 4). AB - In brief: The authors continue their discussion of the physiological responses and adaptations that occur as a result of resistance training. (The discussion began in part 2; part 1 presented the basics of resistance training.) Body composition, neural and cardiovascular adaptations, serum lipid profile, blood pressure, and the endocrine system are covered in this article. The conclusion is that conventional weight training brings about little change in endurance capabilities, but that high-volume, low-load training enhances endurance capabilities and may cause serum lipid profile changes that reduce cardiovascular risk. PMID- 27403550 TI - Athletic Injuries to the Knee: Evaluation Using Magnetic Resonance Imaging. AB - In brief: Specific diagnosis of an athletic injury to the knee can be difficult if based on history and clinical examination alone. In some cases, arthrography has been used to aid in diagnosis; however, the arthrogram-though accurate-has several disadvantages, including the need for injection of contrast material and exposure of the patient to ionizing radiation. A noninvasive and highly accurate alternative for assessing selected knee injuries is magnetic resonance imaging (MRI). The authors briefly review the theory behind MRI, the history of its development, and its specialized terminology; they describe the procedure, the types of pathologic conditions MRI can demonstrate, and its clinical applications in knee injuries. PMID- 27403551 TI - Exercise-Related Sudden Death: Risks and Causes (Part 1 of 2). AB - In brief: Exercise-related sudden death is a clinical syndrome that is well known both to the general public and to the medical community. Autopsy studies of victims have identified multiple structural cardiovascular diseases underlying sudden death in young athletes (aged 30 years and younger). These diseases include myocardial, coronary arterial, aortic, valvular, and cardiac conduction system disorders. In athletes over 30 years of age, the underlying cause is almost invariably severe coronary artery disease. The author discusses these diseases, along with apparent mechanisms of sudden death, clinical points, risks of exercise stress testing, and cardiac rehabilitation, as a basis for attempts to prevent these tragic events. PMID- 27403552 TI - Tibial Pain in an Amenorrheic Runner. AB - A group of experts met to discuss a case from the University of California, Los Angeles, School of Medicine. This case conference is part of a series featuring a variety of sports medicine topics. PMID- 27403553 TI - Eye Injuries in Sports: Results of a Five-Year Study. AB - In brief: From 1982 to 1986, Quebec ophthalmologists reported 869 sports-related eye injuries. Hyphema was the most common injury, with a frequency of 33%. Most injuries occurred in ice hockey, followed by racket sports (32% and 28%, respectively); most of the injured players were not wearing eye protection. The authors suggest that wearing eye protection should be mandatory in some sports and encouraged in many others. PMID- 27403554 TI - Heart Rate Monitors: Validity, Stability, and Functionality. AB - In brief: The validity of 13 commercially available heart rate (HR) monitors was assessed by comparing the monitored values with simultaneous ECG readings. Stability, as well as validity, was measured using several ergometric devices, and functionality was evaluated by analyzing the practical aspects of each device. Results indicate excellent correlations between readings obtained by ECG and HR monitors using conventional chest electrodes to measure electrical activity of the heart. Most of the monitors using other types of electrodes or using an earlobe photocell to measure opacity of blood flow were inadequate. The authors point out functional differences in the monitors to help potential users choose the best one to fit their needs. PMID- 27403556 TI - Recommendations for Participation in Competitive Sports. PMID- 27403555 TI - Exercise and Estrogen in Women's Health: Getting a Clearer Picture. AB - Should exercise and estrogen be used to treat athletic amenorrhea, osteoporosis, cancer, or coronary heart disease? Recent research may help bring the answers into sharper focus. PMID- 27403557 TI - The Seoul Olympics: The 'Autumn' Games. PMID- 27403558 TI - Exercise adviser. PMID- 27403560 TI - Epizootiology of Perkinsus marinus, parasite of the pleasure oyster Crassostrea corteziensis, in the Pacific coast of Mexico. AB - The protozoan parasite Perkinsus marinus is the etiological agent of "dermo disease". This pathogen is considered by the World Organization for Animal Health (OIE) as reportable due to the high mortalities that it produces in the eastern oyster Crassostrea virginica in the US. In 2006, this parasite was detected in the pleasure oyster Crassostrea corteziensis in Nayarit on the Pacific coast of Mexico, indicating a new host and an extension of its known distribution. Epizootiological data of P. marinus in the pleasure oyster are unknown. With the objective of determining the prevalence and intensity in relation with temperature and salinity throughout time, as well as for studying interactions of host size and sex with the parasite, a monthly sampling was carried out in two aquaculture sites of Nayarit from 2007 to 2014. A total of 7700 oysters were analyzed. In both localities, prevalence was low in winter (<6%) when temperature and salinity fluctuated around 24 degrees C and 33, respectively; and the highest prevalence values occurred during summer (37%) when temperature and salinity were around 30 degrees C and 20, respectively. Infection intensity increased in summer, but severe cases remained on average <10%. Larger oysters showed the highest prevalence and intensity, and higher prevalence were generally observed in females. No unusual mortalities directly related with P. marinus were observed. PMID- 27403561 TI - Capturing relativistic wakefield structures in plasmas using ultrashort high energy electrons as a probe. AB - A new method capable of capturing coherent electric field structures propagating at nearly the speed of light in plasma with a time resolution as small as a few femtoseconds is proposed. This method uses a few femtoseconds long relativistic electron bunch to probe the wake produced in a plasma by an intense laser pulse or an ultra-short relativistic charged particle beam. As the probe bunch traverses the wake, its momentum is modulated by the electric field of the wake, leading to a density variation of the probe after free-space propagation. This variation of probe density produces a snapshot of the wake that can directly give many useful information of the wake structure and its evolution. Furthermore, this snapshot allows detailed mapping of the longitudinal and transverse components of the wakefield. We develop a theoretical model for field reconstruction and verify it using 3-dimensional particle-in-cell (PIC) simulations. This model can accurately reconstruct the wakefield structure in the linear regime, and it can also qualitatively map the major features of nonlinear wakes. The capturing of the injection in a nonlinear wake is demonstrated through 3D PIC simulations as an example of the application of this new method. PMID- 27403563 TI - Anomalous High Rainfall and Soil Saturation as Combined Risk Indicator of Rift Valley Fever Outbreaks, South Africa, 2008-2011. AB - Rift Valley fever (RVF), a zoonotic vectorborne viral disease, causes loss of life among humans and livestock and an adverse effect on the economy of affected countries. Vaccination is the most effective way to protect livestock; however, during protracted interepidemic periods, farmers discontinue vaccination, which leads to loss of herd immunity and heavy losses of livestock when subsequent outbreaks occur. Retrospective analysis of the 2008-2011 RVF epidemics in South Africa revealed a pattern of continuous and widespread seasonal rainfall causing substantial soil saturation followed by explicit rainfall events that flooded dambos (seasonally flooded depressions), triggering outbreaks of disease. Incorporation of rainfall and soil saturation data into a prediction model for major outbreaks of RVF resulted in the correctly identified risk in nearly 90% of instances at least 1 month before outbreaks occurred; all indications are that irrigation is of major importance in the remaining 10% of outbreaks. PMID- 27403562 TI - Germline MC1R status influences somatic mutation burden in melanoma. AB - The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of an R allele is estimated to be 42% (95% CI, 15-76%) higher than that among persons without an R allele. This figure is comparable to the expected mutational burden associated with an additional 21 years of age. We also find significant and similar enrichment of non-C>T mutation classes supporting a role for additional mutagenic processes in melanoma development in individuals carrying R alleles. PMID- 27403564 TI - Overcoming the matched-sample bottleneck: an orthogonal approach to integrate omic data. AB - MicroRNAs (miRNAs) are small non-coding RNA molecules whose primary function is to regulate the expression of gene products via hybridization to mRNA transcripts, resulting in suppression of translation or mRNA degradation. Although miRNAs have been implicated in complex diseases, including cancer, their impact on distinct biological pathways and phenotypes is largely unknown. Current integration approaches require sample-matched miRNA/mRNA datasets, resulting in limited applicability in practice. Since these approaches cannot integrate heterogeneous information available across independent experiments, they neither account for bias inherent in individual studies, nor do they benefit from increased sample size. Here we present a novel framework able to integrate miRNA and mRNA data (vertical data integration) available in independent studies (horizontal meta-analysis) allowing for a comprehensive analysis of the given phenotypes. To demonstrate the utility of our method, we conducted a meta analysis of pancreatic and colorectal cancer, using 1,471 samples from 15 mRNA and 14 miRNA expression datasets. Our two-dimensional data integration approach greatly increases the power of statistical analysis and correctly identifies pathways known to be implicated in the phenotypes. The proposed framework is sufficiently general to integrate other types of data obtained from high throughput assays. PMID- 27403565 TI - Studying the Supramolecular Organization of Photosynthetic Membranes within Freeze-fractured Leaf Tissues by Cryo-scanning Electron Microscopy. AB - Cryo-scanning electron microscopy (SEM) of freeze-fractured samples allows investigation of biological structures at near native conditions. Here, we describe a technique for studying the supramolecular organization of photosynthetic (thylakoid) membranes within leaf samples. This is achieved by high-pressure freezing of leaf tissues, freeze-fracturing, double-layer coating and finally cryo-SEM imaging. Use of the double-layer coating method allows acquiring high magnification (>100,000X) images with minimal beam damage to the frozen-hydrated samples as well as minimal charging effects. Using the described procedures we investigated the alterations in supramolecular distribution of photosystem and light-harvesting antenna protein complexes that take place during dehydration of the resurrection plant Craterostigma pumilum, in situ. PMID- 27403566 TI - Visualization of Surface-tethered Large DNA Molecules with a Fluorescent Protein DNA Binding Peptide. AB - Large DNA molecules tethered on the functionalized glass surface have been utilized in polymer physics and biochemistry particularly for investigating interactions between DNA and its binding proteins. Here, we report a method that uses fluorescent microscopy for visualizing large DNA molecules tethered on the surface. First, glass coverslips are biotinylated and passivated by coating with biotinylated polyethylene glycol, which specifically binds biotinylated DNA via avidin protein linkers and significantly reduces undesirable binding from non specific interactions of proteins or DNA molecules on the surface. Second, the DNA molecules are biotinylated by two different methods depending on their terminals. The blunt ended DNA is tagged with biotinylated dUTP at its 3' hydroxyl terminus, by terminal transferase, while the sticky ended DNA is hybridized with biotinylated complimentary oligonucleotides by DNA ligase. Finally, a microfluidic shear flow makes single DNA molecules stretch to their full contour lengths after being stained with fluorescent protein-DNA binding peptide (FP-DBP). PMID- 27403567 TI - Epicuticular Wax in Developing Olives (Olea europaea) Is Highly Dependent upon Cultivar and Fruit Ripeness. AB - The epicuticular wax (EW) layer is located on the surface of most plant organs. It provides the cuticle with most of its properties and is the primary barrier against biotic and abiotic stress. Despite the importance of Olea europaea cultivation, few studies have characterized the EW covering leaves and olives, which could be involved in resistance to both infection and environmental conditions. In the present study, wide-ranging screening was carried out using direct-injection electrospray ionization coupled to high-resolution mass spectrometry to analyze EW in developing olives of nine varieties. The proportions of EW fractions [wax esters (WEs), diacylglycerols, triacylglycerols (TAGs), triterpenic acids, and aldehydes] strongly depended upon the olive cultivar and, in only a few cases, were influenced by the sampling date. The specific compositions of the major fractions, WEs and TAGs, were strictly related to the cultivar, while the degree of unsaturation and chain length of the WEs evolved throughout the 4 weeks prior to the olive turning color. PMID- 27403568 TI - Catalytic Formation of Hydrogen Peroxide from Coenzyme NADH and Dioxygen with a Water-Soluble Iridium Complex and a Ubiquinone Coenzyme Analogue. AB - A ubiquinone coenzyme analogue (Q0: 2,3-dimethoxy-5-methyl-1,4-benzoquinone) was reduced by coenzyme NADH to yield the corresponding reduced form of Q0 (Q0H2) in the presence of a catalytic amount of a [C,N] cyclometalated organoiridium complex (1: [Ir(III)(Cp*)(4-(1H-pyrazol-1-yl-kappaN(2))benzoic acid kappaC(3))(H2O)]2SO4) in water at ambient temperature as observed in the respiratory chain complex I (Complex I). In the catalytic cycle, the reduction of 1 by NADH produces the corresponding iridium hydride complex that in turn reduces Q0 to produce Q0H2. Q0H2 reduced dioxygen to yield hydrogen peroxide (H2O2) under slightly basic conditions. Catalytic generation of H2O2 was made possible in the reaction of O2 with NADH as the functional expression of NADH oxidase in white blood cells utilizing the redox cycle of Q0 as well as 1 for the first time in a nonenzymatic homogeneous reaction system. PMID- 27403569 TI - Mutations in Human Interferon alpha2b Gene and Potential as Risk Factor Associated with Female Breast Cancer. AB - The current study explored the potential links between breast cancer and human interferon alpha-2b (hIFNalpha-2b) gene mutations. The hIFNalpha-2b gene was amplified from breast cancer tumor tissue samples (N = 60) by polymerase chain reaction (PCR) and the products were subjected to gene sequencing. A total of 38 (63.3%) samples showed positive PCR amplification results. Several of these also exhibited frequent alterations (mutations) after 400 bp and, in particular, adenine was replaced by other bases. A total of 19 selected mutated amino acids were analyzed for local/general fold pattern changes. Human IFNalpha-2b receptor (IFNAR): ligand (hIFNalpha-2b protein) interactions through a Z-DOCK (3.0.2) server were also evaluated to assess the binding patterns of each ligand to receptor to induce Janus-Kinase-signal transducer and activator of transcription antiproliferative signal transduction pathway inside the cancer cells. Certain local structural and conformational changes were predicted to be induced by mutations in the ligand. The variant models of the hIFNalpha-2b displayed structural and conformational changes that signified that changes to hIFNalpha-2b may be a risk factor in addition to other known factors associated with onset/progression of female breast carcinoma. It was hoped that others might build upon the research in this study evaluating protein structural models with mutations and their consequent interactions with receptors in the development of potent immune therapeutic drugs for breast cancer that are based on recombinant hIFNalpha-2b. PMID- 27403570 TI - Corrigendum: Synthesis of Reduced Graphene Oxide-Modified LiMn0.75Fe0.25PO4 Microspheres by Salt-Assisted Spray Drying for High-Performance Lithium-Ion Batteries. PMID- 27403571 TI - 2-D image reconstruction of photoacoustic endoscopic imaging based on time reversal. AB - BACKGROUNDS: Photoacoustic endoscopic (PAE) imaging is a rapidly emerging interventional imaging modality for identification and characterization of intraluminal pathological tissues. Since the scanning aperture of PAE is enclosed in the lumen, image reconstruction techniques used in photoacoustic tomography (PAT) can not be directly applied. OBJECTIVE: The purpose of this work is to design an image reconstruction method based on time-reversal (TR) for a PAE imaging catheter equipped with a single-element NFU transducer with circular scanning. METHODS: Firstly, the back-propagation of photoacoustic waves emitted from the tissue absorbers was modeled and simulated. Then, two-dimensional (2-D) grayscale images of the acoustic pressure distribution were obtained displaying the morphological structure of luminal cross-sections. A computer-simulated vessel phantom embedded with atherosclerotic plaques was used to validate and quantitatively evaluate the method. RESULT: The structural similarity (SSIM) of the images reconstructed with TR is comparable to algebraic reconstruction technique (ART), which is at least 65% higher than filtered back-projection (FBP). The time cost of TR is about 16 times that of FBP and 1/4 of ART under the same test condition. CONCLUSION: The reconstructed image quality may degrade when the photoacoustic data are incomplete due to sparse measuring locations and limited-view scanning. The spline interpolation can be used to improve the image quality and eliminate artifacts. PMID- 27403572 TI - Removal of Exogenous Materials from the Outer Portion of Frozen Cores to Investigate the Ancient Biological Communities Harbored Inside. AB - The cryosphere offers access to preserved organisms that persisted under past environmental conditions. In fact, these frozen materials could reflect conditions over vast time periods and investigation of biological materials harbored inside could provide insight of ancient environments. To appropriately analyze these ecosystems and extract meaningful biological information from frozen soils and ice, proper collection and processing of the frozen samples is necessary. This is especially critical for microbial and DNA analyses since the communities present may be so uniquely different from modern ones. Here, a protocol is presented to successfully collect and decontaminate frozen cores. Both the absence of the colonies used to dope the outer surface and exogenous DNA suggest that we successfully decontaminated the frozen cores and that the microorganisms detected were from the material, rather than contamination from drilling or processing the cores. PMID- 27403573 TI - Magnetic resonance volumetric measurement of endolymphatic space in patients without vertiginous or cochlear symptoms. AB - CONCLUSION: Magnetic resonance volumetric measurement of inner ear endolymphatic space (ELS) was performed in patients without vertiginous or cochlear symptoms. The existence of the ELS in patients with chronic rhinosinusitis (CRS) was shown. The ELS in the cochlea and vestibule was classified into four categories. These findings could be useful as a standard reference for further research. OBJECTIVES: To identify normal values of the ELS in the cochlea and vestibule. METHODS: Twenty-four patients with CRS were enrolled. Inner ear fluid space images and positive perilymph/positive endolymph images were acquired using a 3.0 tesla unit. Three-dimensional (3-D) images were constructed semi-automatically using both anatomical and tissue information by fusing the 3-D images of the inner ear fluid space and the ELS. RESULTS: Among all patients, the mean ELS/the total fluid space (TFS) ratio in the cochlea was 8.8% and that in the vestibule was 16.2%. The ELS in the cochlea and vestibule was classified into four categories. Age-related differences were found in the TFS, ELS, and ELS/TFS ratio in the inner ear and the ELS and ELS/TFS ratio in the vestibule. PMID- 27403574 TI - One-Pot Coupling-Coupling-Cyclocondensation Synthesis of Fluorescent Pyrazoles. AB - Consecutive four-component coupling-coupling-cyclocondensation syntheses of pyrazoles and pyrimidines were developed by taking advantage of the provisional, sequentially Pd-catalyzed one-pot generation of alkynones from aryl iodides, ethynylmagnesium bromide, and acid chlorides. This one-pot methodology allows the concise, diversity-oriented generation of a set of donor-, acceptor-, and donor acceptor-substituted pyrazoles, which are interesting fluorophores. Most distinctly, donor-acceptor pyrazoles display remarkably red-shifted emission maxima and pronounced positive solvochromicity, spanning an overall range from 363 nm (cyclohexane) to 595 nm (acetonitrile). DFT and TD-DFT calculations elucidate the electronic structure and the photophysical behavior. Upon photonic excitation, considerable charge-transfer character becomes apparent, which rationalizes the origin of huge Stokes shifts and solvochromic behavior. PMID- 27403576 TI - Involvement of Antioxidant System in the Amelioration of Scopolamine-Induced Memory Impairment by Grains of Paradise (Aframomum melegueta K. Schum.) Extract. AB - Background: Grains of paradise (Aframomum melegueta) K. Schum is used to flavour foods and used as memory enhancer and anti-aging in traditional African medicine. This study examine the influence of ethanolic seed extract of Aframomum melegueta (AFM) on cognitive impairment induced by scopolamine in rodents. Methods: AFM (6.25, 12.5 or 25 mg/kg, p.o.) or tacrine (5 mg/kg, i.p.) was administered for 3 consecutive days, 1 h post-treatment on day 3, scopolamine (3 mg/kg, i.p.) was given, 5 min later, cognition was evaluated in the Y-maze and elevated plus maze (EPM) tests in mice as well as the Morris water maze (MWM) paradigm in rats. Biomarkers of oxidative stress in the prefrontal cortex, striatum and hippocampus of rats were evaluated after the MWM task. The antioxidant capacity of AFM was evaluated in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion reducing power (FRAP) assays. Results: Scopolamine significantly reduced (38.72%) spontaneous alternation behavior in the Y-maze and increase in transfer latency in the EPM test on day 2, which was ameliorated by AFM (25 mg/kg; 49.86%, 71.55%, respectively) in mice. In addition, AFM prevented the spatial learning deficit induced by scopolamine in the MWM task. Similarly, scopolamine-induced oxidative-nitrosative stress was attenuated by AFM treatment, evidenced in decreased malondialdehyde and nitrite levels, restoration of glutathione and superoxide dismutase levels. Interestingly, AFM exhibited notable scavenging activities against DPPH, NO and FRAP radicals. Conclusion: These results showed that A. melegueta seed extract prevented scopolamine-induced memory impairments through enhancement of antioxidant defense systems. PMID- 27403577 TI - The Effect of Caffeine and chk2 Inhibitor on Doxorubicin-Induced Cellular Senescence in MCF-7 Cells. AB - Senescence is cellular growth arrest. Induction of senescence can be considered as an alternative approach for treating cancer cells being resistance to anti cancer drugs. We investigated the effect of caffeine and chk2 inhibitor on doxorubicin induced senescence in MCF-7 cells. Caffeine and chk2 inhibitor were used in combination with doxorubicin. Cellular senescence was assessed by beta galactosidase assay. P21 expression was determined using immunoblotting. Cell proliferation was evaluated using prestoblue assay. Results revealed that doxorubicin induced senescence and increased p21 expression in MCF-7 cells. However, co-treatment of chk2 inhibitor and caffeine with doxorubicin could not augment doxorubicin-induced senescence. Moreover, p21 expression was decreased in combination studies compared to doxorubicin group. Our results indicate that caffeine, chk2 inhibitor and combination of chk2 inhibitor, caffeine and doxorubicin could not increase sensitivity of the cells to doxorubicin-induced senescence. Our findings demonstrate that low-dose doxorubicin induced senescence via the activation of ATM, -chk2, and -p21 pathways, while inhibition of ATM and chk2 cannot consider as a new target for sensitization of MCF-7 cells to doxorubicin. Thus, chk2 inhibitor and caffeine might not serve as desirable agents being capable to restore chemo sensitivity in doxorubicin-resistant breast tumors. PMID- 27403578 TI - Applications of Copolymeric Nanoparticles in Drug Delivery Systems. AB - Nanoparticles have outstanding compensate compared with other drug carriers, as a result of their small particle size and bulky and changeable surface. Recently, block copolymers have get imaginary movement on the continuing research in the area of drug delivery technology, because of their potential to afford a biomaterial having an extensive series of amphiphilic personality, in addition to targeting the drugs to specific position. Block copolymers are prepared up of blocks of different polymerized monomers. Between the block copolymers, amphiphilic block copolymers can self-assemble to form nano-sized vehicles, for example micelles, liposomes, polymerases and hydrogels in aqueous or non-aqueous media. This review evaluated the synthesis, construction, and major applications of amphiphilic block copolymer and analogous vehicles in order to provide an overview of the present features of functionalized block copolymers for drug delivery applications. PMID- 27403579 TI - Effect of Vesicle-to-Micelle Transition on the Interactions of Phospholipid/Sodium Cholate Mixed Systems with Curcumin in Aqueous Solution. AB - The role of vesicle-to-micelle transition has been investigated in the interactions of phospholipid vesicles, phospholipid/sodium cholate (NaC) mixed vesicles, and phospholipid/NaC mixed micelles with curcumin in aqueous solution. The addition of NaC causes phospholipid vesicles to transit into phospholipid/NaC mixed vesicles and phospholipid/NaC mixed micelles. Turbidity measurement reveals that the presence of curcumin increases the NaC concentration for the solubilization of phospholipid vesicles, which indicates that the bound curcumin tends to suppress the vesicle-to-micelle transition. The pyrene polarity index and curcumin fluorescence anisotropy measurements suggest that phospholipid/NaC mixed micelles have a more compact structure than that of phospholipid vesicles and phospholipid/NaC mixed vesicles. Curcumin associated with phospholipid vesicles, phospholipid/NaC mixed vesicles, and phospholipid/NaC mixed micelles often results in higher intensities of absorption and fluorescence than those of free curcumin. However, phospholipid/NaC mixed vesicles lead to the highest values of absorption and fluorescence intensities, binding constant, and radical scavenging capacity with curcumin. The different structures in the phospholipid bilayer of phospholipid/NaC mixed vesicles and the hydrophobic part of phospholipid/NaC mixed micelles where curcumin located are discussed to explain the interaction behaviors of phospholipid/NaC mixed systems with curcumin. PMID- 27403580 TI - Tuning the synthesis of platinum-copper nanoparticles with a hollow core and porous shell for the selective hydrogenation of furfural to furfuryl alcohol. AB - Pt-Cu nanoparticles constructed with a hollow core and porous shell have been synthesized in which Pt-Cu cages with multiporous outermost shells are formed at the initial stage and then the Pt and Cu atoms in solution continuously fed these hollow-core of cages by passing through the porous tunnels of the outermost shells, finally leading to the formation of hollow structures with different sizes. Furthermore, these hollow-core Pt-Cu nanoparticles are more effective than the solid-core Pt-Cu nanoparticles for the catalytic hydrogenation of furfural toward furfuryl alcohol. The former can achieve almost 100% conversion of furfural with 100% selectivity toward the alcohol. PMID- 27403581 TI - Crystal structures of peptidic catalysts of the H-dPro-Pro-Xaa type. AB - Crystal structures of catalytically active tripeptides of the general type H-dPro Pro-Xaa and related N-acetylated analogs were compared. The influence of acylation at the N-terminus, the nature of the C-terminal residue, coordinating groups, and intramolecular hydrogen bonds on the conformation of the tripeptides was examined. Regardless of the presence or absence of stabilizing intramolecular H-bonds or n -> pi* interactions, all of the analyzed peptides share a beta-turn like conformation, which highlights the structural rigidity of the dPro-Pro motif and its value for conformational preorganization. The C-terminal residues and coordinating moieties were found to affect the turn-conformation, which suggests that H-dPro-Pro-Xaa type peptides are sufficiently flexible to adopt distinctly different but related conformations. PMID- 27403583 TI - Foreword. PMID- 27403582 TI - Diverse architectural properties of Sso10a proteins: Evidence for a role in chromatin compaction and organization. AB - Sso10a proteins are small DNA-binding proteins expressed by the crenarchaeal model organism Sulfolobus solfataricus. Based on the structure of Sso10a1, which contains a winged helix-turn-helix motif, it is believed that Sso10a proteins function as sequence-specific transcription factors. Here we show that Sso10a1 and Sso10a2 exhibit different distinct DNA-binding modes. While the ability to bend DNA is shared between the two proteins, DNA bridging is observed only for Sso10a1 and only Sso10a2 exhibits filament formation along DNA. The architectural properties of Sso10a proteins suggest that these proteins fulfil generic roles in chromatin organization and compaction. As these proteins exhibit different binding behaviour depending on their DNA binding stoichiometry, altered levels of expression in the cell can be exploited to drive changes in local genome folding, which may operate to modulate transcription. PMID- 27403584 TI - Practical Work-up and Management of Recurrent Pregnancy Loss for the Front-Line Clinician. AB - Only a few so-called etiologies of recurrent pregnancy loss recurrent pregnancy loss in otherwise healthy women are adequately supported by well-designed investigations of association. The majority of proposed "treatments" have not been subjected to rigorous trials. The American Board of Internal Medicine Choosing Wisely initiative urges providers and patients to have constructive dialog aimed at choosing health care that is supported by evidence, not duplicative of other tests or procedures already received, free from harm, and truly necessary. We support the refreshing, objective frankness promoted by this campaign. A version of the Choosing Wisely "Do" and "Don't" format for recurrent pregnancy loss is presented. PMID- 27403585 TI - Reproductive Endocrinology in Recurrent Pregnancy Loss. AB - Endocrine disruptions may be important in patients experiencing recurrent pregnancy loss (RPL). This review focuses on data available on RPL and the endocrine system to investigate relevant, and perhaps modifiable, endocrine factors of importance for the disorder. Evidence indicates that some hormones may be important as immune modulators and a better understanding of this interplay has potential for improving pregnancy outcome in RPL. To date there is a lack of consensus on the effect of endocrine treatment options in RPL and there is a strong need for large randomized-controlled trials. PMID- 27403586 TI - Orthopedic Injury in Pregnancy. AB - There are many reasons why a woman's pregnancy can put her at risk for orthopedic pain and injury. Given the high percentage of pregnant patients experiencing some degree of musculoskeletal pain, it is surprising that this is not an area of wider study. This chapter takes an evidence based approach to help the reader understand the implications of the numerous anatomic and physiologic changes associated with the gravid state, and how they act to promote both discomfort and injury. One-third of pregnant women in America are obese, further increasing risk. Exercise in most pregnancies is recommended and regarded as safe and thus obstetric care providers need to understand risk, diagnostic techniques and treatments. PMID- 27403587 TI - Mechanistic Insights into C-H Oxidations by Ruthenium(III)-Pterin Complexes: Impact of Basicity of the Pterin Ligand and Electron Acceptability of the Metal Center on the Transition States. AB - A ruthenium(II) complex, [Ru(dmdmp)Cl(MeBPA)] (2) (Hdmdmp = N,N-dimethyl-6,7 dimethylpterin, MeBPA = N-methyl-N,N-bis(pyridylmethyl)amine), having a pterin derivative as a proton-accepting ligand, was synthesized and characterized. Complex 2 shows higher basicity than that of a previously reported Ru(II)-pterin complex, [Ru(dmdmp) (TPA)](+) (1) (TPA = tris(2-pyridylmethyl)amine). On the other hand, 1e(-)-oxidized species of 1 (1OX) exhibits higher electron acceptability than that of 1e(-)-oxidized 2 (2OX). Bond dissociation enthalpies (BDE) of the two Ru(II) complexes having Hdmdmp as a ligand in proton-coupled electron transfer (PCET) to generate 1OX and 2OX were calculated to be 85 kcal mol(-1) for 1OX and 78 kcal mol(-1) for 2OX. The BDE values are large enough to perform H atom transfer from C-H bonds of organic molecules to the 1e(-)-oxidized complexes through PCET. The second-order rate constants (k) of PCET oxidation reactions were determined for 1OX and 2OX. The logarithms of normalized k values were proportional to the BDE values of C-H bonds of the substrates with slopes of -0.27 for 1OX and -0.44 for 2OX. The difference between 1OX and 2OX in the slopes suggests that the transition states in PCET oxidations of substrates by the two complexes bear different polarization, as reflection of difference in the electron acceptability and basicity of 1OX and 2OX. The more basic 2OX attracts a proton from a C-H bond via a more polarized transition state than that of 1OX; on the contrary, the more electron-deficient 1OX forms less polarized transition states in PCET oxidation reactions of C-H bonds. PMID- 27403588 TI - Noncovalent PEGylation via Lectin-Glycopolymer Interactions. AB - PEGylation, the covalent modification of proteins with polyethylene glycol, is an abundantly used technique to improve the pharmacokinetics of therapeutic proteins. The drawback with this methodology is that the covalently attached PEG can impede the biological activity (e.g., reduced receptor-binding capacity). Protein therapeutics with "disposable" PEG modifiers have potential advantages over the current technology. Here, we show that a protein-polymer "Medusa complex" is formed by the combination of a hexavalent lectin with a glycopolymer. Using NMR spectroscopy, small-angle X-ray scattering (SAXS), size exclusion chromatography, and native gel electrophoresis it was demonstrated that the fucose-binding lectin RSL and a fucose-capped polyethylene glycol (Fuc-PEG) form a multimeric assembly. All of the experimental methods provided evidence of noncovalent PEGylation with a concomitant increase in molecular mass and hydrodynamic radius. The affinity of the protein-polymer complex was determined by ITC and competition experiments to be in the micromolar range, suggesting that such systems have potential biomedical applications. PMID- 27403589 TI - Bonding-restricted structure search for novel 2D materials with dispersed C2 dimers. AB - Currently, the available algorithms for unbiased structure searches are primarily atom-based, where atoms are manipulated as the elementary units, and energy is used as the target function without any restrictions on the bonding of atoms. In fact, in many cases such as nanostructure-assembled materials, the structural units are nanoclusters. We report a study of a bonding-restricted structure search method based on the particle swarm optimization (PSO) for finding the stable structures of two-dimensional (2D) materials containing dispersed C2 dimers rather than individual C atoms. The C2 dimer can be considered as a prototype of nanoclusters. Taking Si-C, B-C and Ti-C systems as test cases, our method combined with density functional theory and phonon calculations uncover new ground state geometrical structures for SiC2, Si2C2, BC2, B2C2, TiC2, and Ti2C2 sheets and their low-lying energy allotropes, as well as their electronic structures. Equally important, this method can be applied to other complex systems even containing f elements and other molecular dimers such as S2, N2, B2 and Si2, where the complex orbital orientations require extensive search for finding the optimal orientations to maximize the bonding with the dimers, predicting new 2D materials beyond MXenes (a family of transition metal carbides or nitrides) and dichalcogenide monolayers. PMID- 27403590 TI - Superhydrophobic Coatings with Edible Materials. AB - We used FDA-approved, edible materials to fabricate superhydrophobic coatings in a simple, low cost, scalable, single step process. Our coatings display high contact angles and low roll off angles for a variety of liquid products consumed daily and facilitate easy removal of liquids from food containers with virtually no residue. Even at high concentrations, our coatings are nontoxic, as shown using toxicity tests. PMID- 27403591 TI - Hippocampal volume in first-episode schizophrenia and longitudinal course of the illness. AB - OBJECTIVES: Several lines of evidence suggest an adverse effect of psychotic episodes on brain morphology. It is not clear if this relationship reflects the cumulative effect of psychotic outbursts on the gradual progressive reduction of hippocampal tissue or an increased tendency toward psychotic episodes in patients with a smaller hippocampus at the beginning of the illness. METHODS: This is a longitudinal 4-year prospective study of patients with first-episode schizophrenia (FES, N = 58). Baseline brain anatomical scans (at FES) were analysed using voxel-based morphometry and atlas-based volumetry of the hippocampal subfields. The effects of first-episode duration on the hippocampal morphology, and the effect of baseline hippocampal morphology on illness course with relapses, number of psychotic episodes and residual symptoms were analysed. RESULTS: A significant negative correlation was detected between first-episode duration and baseline hippocampal morphology. Relapse, number of psychotic episodes and residual symptoms had no correlation with baseline hippocampal volume. CONCLUSIONS: We replicated the effect of psychosis duration on hippocampal volume already at the time first-episode, which supports the concept of toxicity of psychosis. The indices of a later unfavourable course of schizophrenia had no correlation with baseline brain morphology, suggesting that there is no baseline morphological abnormality of the hippocampus that predisposes the patient to frequent psychotic outbursts. PMID- 27403592 TI - Cloning and differential expression of a novel toll-like receptor gene in noble scallop Chlamys nobilis with different total carotenoid content. AB - To investigate whether toll like receptors (TLRs) genes do have an immune influence on noble scallop Chlamys nobilis under pathogen stress, acute challenges lasting 48 h to Vibrio parahaemolyticus, lipopolysaccharide (LPS), polyinosinic polycytidylic acid (Poly I:C), and PBS were conducted in two scallop stains of orange and brown with different carotenoids content. A novel toll-like receptor gene called CnTLR-1 was cloned and its transcripts under different challenges were determined. Meantime, total carotenoids content (TCC) of different immune responses were determined to investigate whether there was a relationship between gene expression and carotenoids content. The full length cDNA of CnTLR-1 is 2982 bp with an open reading frame (ORF) of 1920 bp encoding 639-deduced amino acids, which contains five leucine-rich repeats (LRR), two LRR C-terminal (LRRCT) motifs and a LRR-N-terminal (LRRNT) motif in the extracellular domain, a transmembrane domain and a Toll/Interleukin-1 Receptor (TIR) of 138 amino acids in the cytoplasmic region. Phylogenetic tree analysis showed that CnTLR-1 could be clustered with mollusk TLRs into one group and especially was related closely to Crassostrea gigas and Mytilus galloprovincialis TLRs. CnTLR-1 transcripts were detected in decreasing levels in the mantle, hemocytes, gill, kidney, gonad, hepatopancreas, intestines and adductor. Compared with PBS control group, CnTLR-1 transcripts were up-regulated in V. parahaemolyticus, LPS and Poly I:C groups. Further, CnTLR-1 transcripts were significantly higher in orange scallops than that of brown ones with and without pathogenic challenges. TCC, which is higher in orange scallops, was initially increased and then decreased during a 48 h immune challenge in the hemocytes. The present results indicate that CnTLR-1 is an important factor involved in the immune defense against pathogens in the noble scallop. PMID- 27403593 TI - A galectin from Hyriopsis cumingii involved in the innate immune response against to pathogenic microorganism and its expression profiling during pearl sac formation. AB - Hyriopsis cumingii is the most important freshwater pearl mussel cultured in China. The operation for implantation is one necessary technical step for pearl culture. However, implantation-induced trauma results in a series of immune responses and can enable the invasion of pathogenic microbes. Lectin proteins are found widely in nature and play important roles in innate immunity. Galectins are members of the lectin superfamily and are characterized by one or several carbohydrate recognition domains (CRDs) that produce multiple sugar binding sites on the protein. Here we cloned and characterized the H. cumingii galectin gene HcGal1, which encodes a 312 amino acid galectin protein. The HcGal1 transcript was detected in all tested H. cumingii tissues and showed higher expression specifically in immune tissues. The significant upregulation of HcGal1 expression was observed after challenging the mussel with lipopolysaccharide or Gram negative and Gram-positive bacteria. After implantation, significant downregulation of the HcGal1 transcript was noted in the mantle, hemocytes, and pearl sac in the acute-stress stage (0-24 h) and the stage of wound healing and pearl-sac formation (24 h-7 d). In addition, significant upregulation of HcGal1 expression was observed in the liver in the stage of wound healing and pearl-sac formation. In the pearl-secretion stage (7-35 d), the HcGal1 transcript levels returned to normal in all tested tissues. We also show that recombinantly expressed and purified HcGal1 can agglutinate some Gram-negative and Gram positive bacteria. In addition, in vivo experiments showed that the recombinant protein HcGal1 could promote phagocytosis by hemocytes. Our data suggest that HcGal1 plays a role in innate immune responses involved in pathogen recognition and wound healing. PMID- 27403594 TI - Steroid hormone "cortisone" and "20-hydroxyecdysone" involved in the non-specific immune responses of white shrimp (Litopenaeus vannamei). AB - This study investigated the effect of two steroid hormones on phenoloxidase activity, O2(-) production in the haemocytes, total haemocyte count (THC), superoxide dismutase (SOD) activity, glutamate oxaloacetate transaminase (GOT) activity, glutamate pyruvate transaminase (GPT) activity, and plasma cholesterol concentrations in white shrimps (Litopenaeus vannamei). Phenoloxidase activity, THC and plasma cholesterol concentration in shrimps treated with cortisone and 20 hydroxyecdysone were found to be lower when compared with the control groups. In the observation of O2(-) production, treatment of cortisone and hydroxyecdysone were reducing the activity in the 1st day, but to be undiversified with the elapsed time. By contrast, SOD activity in the hepatopancreas, plasma GOT activity, and GPT activity were significantly increased when compared with the control groups. PMID- 27403595 TI - Optimization of efficacy of a live attenuated Flavobacterium psychrophilum immersion vaccine. AB - This study was aimed at optimizing the efficacy of a recently developed live attenuated immersion vaccine (B.17-ILM) as a promising vaccine against bacterial coldwater disease (BCWD) caused by Flavobacterium psychrophilum in salmonids. Rainbow trout (RBT) fry were vaccinated by immersion, and different parameters affecting vaccination such as fish size, vaccine delivery time, dose, duration of protection, booster regimes and vaccine growth incubation time were optimized. Specific anti-F. psychrophilum immune response was determined by ELISA. Protective efficacy was determined by challenging with a virulent strain of F. psychrophilum (CSF-259-93) and calculating cumulative percent mortality (CPM) and relative percent survival (RPS). All vaccinated fish developed significantly higher levels of serum antibody titers by week 8 when compared to their respective controls. Immersion vaccination for 3, 6 and 30 min produced significant protection with comparable RPS values of 47%, 53% and 52%, respectively. This vaccine provided significant protection for fish as small as 0.5 g with an RPS of 55%; larger fish of 1 g and 2 g yielded slightly higher RPS values of 59% and 60%, respectively. Fish vaccinated with higher vaccine doses of ~10(10) and 10(8) colony forming units mL(-1) (cfu ml(-1)) were strongly protected out to at least 24 weeks with RPS values up to 70%. Fish vaccinated with lower doses (~10(6) and 10(5) cfu mL(-1)) had good protection out to 12 weeks, but RPS values dropped to 36% and 34%, respectively by 24 weeks. Vaccine efficacy was optimum when the primary vaccination was followed by a single booster (week 12 challenge RPS = 61%) rather than two boosters (week 12 challenge RPS = 48%). Vaccination without a booster resulted in a lower RPS (13%) indicating the necessity of a single booster vaccination to maximize efficacy. This study presents key findings that demonstrate the efficacy and commercial potential for this live attenuated BCWD vaccine. PMID- 27403596 TI - Kraftionema allantoideum, a new genus and family of Ulotrichales (Chlorophyta) adapted for survival in high intertidal pools. AB - The marine, sand-dwelling green alga Kraftionema allantoideum gen. et sp. nov. is described from clonal cultures established from samples collected in coastal, high intertidal pools from south eastern Australia. The species forms microscopic, uniseriate, unbranched, 6-8 MUm wide filaments surrounded by a gelatinous capsule of varying thickness. Filaments are twisted, knotted, and variable in length from 4 to 50 cells in field samples but straighter and much longer in culture, up to 1.5 mm in length. Cell division occurs in several planes, resulting in daughter cells of varying shape, from square to rectangular to triangular, giving rise to gnarled filaments. Mature cells become allantoid, elongate with rounded ends, before dividing one time to form bicells comprised of two domed cells. Adjacent bicells separate from one another and mature filaments appeared as a string of loosely arranged sausages. A massive, single, banded chloroplast covered 3/4 of the wall circumference, and contained a single large pyrenoid encased in a starch envelope that measures 1.5-2.5 MUm. Filaments were not adhesive nor did they produce specialized adhesive cells or structures. Reproduction was by fragmentation with all cells capable of producing a new filament. No motile or reproductive cells were observed. Filaments in culture grew equally well in freshwater or marine media, as well as at high salinity, and cells quickly recovered from desiccation. Phylogenetic analysis based on the nuclear-encoded small subunit ribosomal RNA (18S) shows the early branching nature of the Kraftionema lineage among Ulotrichales, warranting its recognition as a family (Kraftionemaceae). PMID- 27403597 TI - Metabolomics in necrotizing enterocolitis: the state of the art. AB - INTRODUCTION: Necrotizing enterocolitis (NEC) is a serious inflammation of the bowel that most often affects premature infants. The exact cause of NEC is still poorly understood but investigators believe that these different factors can play an important role: prematurity and immaturity of the intestine of the preterm newborns, differences in the intestinal bacterial colonization and an abnormal immune response. Since the early symptoms of NEC are often rather non-specific, the diagnosis of NEC can be difficult. Therefore, the search for diagnostic biomarkers for NEC remains warranted. This review focuses on the results of recent metabolomics investigations on NEC, providing important contributions to the understanding of the biochemical process characterizing this disease. Areas covered: Only a few metabolomics applications of NEC are reported in the literature. The metabolic pathway principally altered in NEC patients is suggested to be linked to the carbohydrates metabolism and the role of gluconate as a predictive marker for this pathology is investigated. Expert commentary: Biomarkers are crucial as a confident diagnostic tool to make NEC therapy more efficient. Although only a few metabolomics studies have been performed in NEC research, this technique proved to be helpful to understand the pathophysiological mechanisms of this disease. PMID- 27403599 TI - Physicians' Reactions to Patients Taking a Position: Sequence Analysis of Admission Interviews in Orthopedic Rehabilitation. AB - Little is known about how patients influence health care providers' communication behavior, although this knowledge may contribute to the understanding of the reciprocal influence of patient and provider communication and the pathways between communication and health care outcomes. Therefore, the aim of this study was to explore patients' active communication behaviors and how this affects the immediate communication behavior of physicians. We coded 27 admission interviews from three German orthopedic rehabilitation centers with an adapted version of the Roter Interaction Analysis System. The data were analyzed using correlations and sequence analysis, specifically lag analysis. In this article, we report findings in relation to patients taking a position and physicians' reactions. The analysis showed that while all patients took up a position during their consultation, they very rarely contradicted the physician. Moreover, many instances of patients' expression of opinion were strongly determined by physicians' behavior. When physicians asked patients for their opinions they often used alternative questions or closed questions that limited patients' answering possibilities. While the lag analyses showed that patient communication behavior can influence physician communication, in the majority of instances patients' expression of opinions did not lead to a discussion or shared decision making. PMID- 27403598 TI - Genetic contribution to variation in DNA methylation at maternal smoking sensitive loci in exposed neonates. AB - Epigenome-wide DNA methylation association studies have identified highly replicable genomic loci sensitive to maternal smoking during gestation. The role of inter-individual genetic variation in influencing DNA methylation, leading to the possibility of confounding or bias of such associations, has not been assessed. We investigated whether the DNA methylation levels at the top 10 CpG sites previously associated with exposure to maternal smoking during gestation were associated with individual genetic variation at the genome-wide level. Genome-wide association tests between DNA methylation at the top 10 candidate CpG and genome-wide SNPs were performed in 736 case and control participants of the California Childhood Leukemia Study. Three of the strongest maternal-smoking sensitive CpG sites in newborns were significantly associated with SNPs located proximal to each gene: cg18146737 in the GFI1 gene with rs141819830 (P = 8.2*10 44), cg05575921 in the AHRR gene with rs148405299 (P = 5.3*10-10), and cg12803068 in the MYO1G gene with rs61087368 (P = 1.3*10-18). For the GFI1 CpG cg18146737, the underlying genetic variation at rs141819830 confounded the association between maternal smoking and DNA methylation in our data (the regression coefficient changed from -0.02 [P = 0.139] to -0.03 [P = 0.015] after including the genotype). Our results suggest that further studies using DNA methylation at cg18146737, cg05575921, or cg12803068 that aim to assess exposure to maternal smoking during gestation should include genotype at the corresponding SNP. New methods are required for adequate and routine inclusion of genotypic influence on DNA methylation in epigenome-wide association studies to control for potential confounding. PMID- 27403600 TI - Bursaphelenchus xylophilus is killed by homologues of 2-(1-undecyloxy)-1-ethanol. AB - 2-(1-Undecyloxy)-1-ethanol, monochamol, is a male-produced aggregation pheromone of the Monochamus species, which are efficient vectors of the pine wood nematode (PWN), Bursaphelenchus xylophilus, which cause devastating damage to pines worldwide. The nematicidal activity of synthetic monochamol and its homologues (ROEtOH: R = C7-C13) were investigated to find potential alternatives to the currently used PWN control agents abamectin and emamectin. Compounds with C7-C13 chain length alkyl groups exhibited 100% nematicidal activity at a concentration of 1000 mg/L. At a concentration of 100 mg/L, 2-(1-nonyloxy)-1-ethanol (C9OEtOH), 2-(1-decyloxy)-1-ethanol (C10OEtOH), 2-(1-undecyloxy)-1-ethanol (C11OEtOH), and 2 (1-dodecyloxy)-1-ethanol (C12OEtOH) showed 100% nematicidal activity, but the others showed weaker activities. C11OEtOH showed similar nematicidal activity to abamectin in terms of LD90 values, which were 13.30 and 12.53 mg/L, respectively. However, C9OEtOH, C10OEtOH, and C12OEtOH (LC90 values: 53.63, 38.18, and 46.68 mg/L, respectively) were less effective than C11OEtOH and abamectin. These results indicate that monochamol could be an effective alternative agent against PWN. The relationship of insecticidal and nematicidal activity to different carbon chain lengths in compounds is discussed. PMID- 27403601 TI - Chest Pain in a 39-Year-Old Man: What Could Be the Underlying Cause? PMID- 27403604 TI - The beta2-Adrenoceptor Agonist Terbutaline Stimulates Angiogenesis via Akt and ERK Signaling. AB - Angiogenesis is associated with changes in endothelial cell (EC) proliferation and tube formation, controlled by extracellular receptor-activated kinase (ERK)/mitogen activated protein kinase (MAPK) and Akt signaling. Important regulators of these systems include hormones acting on G-protein-coupled receptors, such as beta 2-adrenoceptors (beta2-ARs). In central nervous system (CNS) trauma, the importance of beta2-AR modulation has been highlighted, although the effects on revascularization remain unclear. Vascular protection and revascularization are, however, key to support regeneration. We have investigated the angiogenic capacity of the specific beta2-AR agonist terbutaline on ECs derived from the CNS, namely bEnd.3-cells. As angiogenesis is a multistep process involving increased proliferation and tube formation of ECs, we investigated the effects of terbutaline on these processes. We show that terbutaline significantly induced bEnd.3 tube formation in a matrigel in vitro assay. Moreover, administration of specific inhibitors of ERK and Akt signaling both inhibited terbutaline-induced tube formation. The proliferation rate of the ECs was not affected. In order to investigate the general effects of terbutaline in an organotypic system, we have used the chick chorioallantoic membrane (CAM)-assay. Most importantly, terbutaline increased the number of blood vessels in this in ovo setting. Although we observed a positive trend, the systemic administration of terbutaline did not significantly improve the functional outcome, nor did it affect revascularization in our spinal cord injury model. In conclusion, these data indicate that terbutaline is promising to stimulate blood vessel formation, underscoring the importance of further research into the angiotherapeutic relevance of terbutaline and beta2-AR signaling after CNS-trauma. J. Cell. Physiol. 232: 298-308, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27403603 TI - Neuronal Trans-Differentiation in Prostate Cancer Cells. AB - BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer (PCa) is an aggressive phenotype associated with therapy resistance. The complete phenotype of these cells is poorly understood. Clinical classification is based predominantly on the expression of standard NE markers. METHODS: We analyzed the phenotype of NE carcinoma of the prostate utilizing in vitro methods, in silico, and immunohistochemical analyses of human disease. RESULTS: LNCaP cells, subjected to a variety of stressors (0.1% [v/v] fetal bovine serum, cyclic AMP) induced a reproducible phenotype consistent with neuronal trans-differentiation. Cells developed long cytoplasmic processes resembling neurons. As expected, serum deprived cells had decreased expression in androgen receptor and prostate specific antigen. A significant increase in neuronal markers also was observed. Gene array analysis demonstrated that LNCaP cells subjected to low serum or cAMP showed statistically significant manifestation of a human brain gene expression signature. In an in silico experiment using human data, we identified that only hormone resistant metastatic prostate cancer showed enrichment of the "brain profile." Gene ontology analysis demonstrated categories involved in neuronal differentiation. Three neuronal markers were validated in a large human tissue cohort. CONCLUSION: This study proposes that the later stages of PCa evolution involves neuronal trans-differentiation, which would enable PCa cells to acquire independence from the neural axis, critical in primary tumors. Prostate 76:1312 1325, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27403605 TI - Near-Field, On-Chip Optical Brownian Ratchets. AB - Nanoparticles in aqueous solution are subject to collisions with solvent molecules, resulting in random, Brownian motion. By breaking the spatiotemporal symmetry of the system, the motion can be rectified. In nature, Brownian ratchets leverage thermal fluctuations to provide directional motion of proteins and enzymes. In man-made systems, Brownian ratchets have been used for nanoparticle sorting and manipulation. Implementations based on optical traps provide a high degree of tunability along with precise spatiotemporal control. Here, we demonstrate an optical Brownian ratchet based on the near-field traps of an asymmetrically patterned photonic crystal. The system yields over 25 times greater trap stiffness than conventional optical tweezers. Our technique opens up new possibilities for particle manipulation in a microfluidic, lab-on-chip environment. PMID- 27403606 TI - Automated cervical precancerous cells screening system based on Fourier transform infrared spectroscopy features. AB - Fourier transform infrared (FTIR) spectroscopy technique can detect the abnormality of a cervical cell that occurs before the morphological change could be observed under the light microscope as employed in conventional techniques. This paper presents developed features extraction for an automated screening system for cervical precancerous cell based on the FTIR spectroscopy as a second opinion to pathologists. The automated system generally consists of the developed features extraction and classification stages. Signal processing techniques are used in the features extraction stage. Then, discriminant analysis and principal component analysis are employed to select dominant features for the classification process. The datasets of the cervical precancerous cells obtained from the feature selection process are classified using a hybrid multilayered perceptron network. The proposed system achieved 92% accuracy. PMID- 27403607 TI - Photobiomodulation: An Accepted Therapeutic Modality? PMID- 27403608 TI - Lipid-based Nutrient Supplements Do Not Affect Gut Bifidobacterium Microbiota in Malawian Infants: A Randomized Trial. AB - OBJECTIVES: The aim of the study was to assess the effect of nutritional supplementation with lipid-based nutrient supplements (LNS) and corn-soy blend flour on Bifidobacterium and Staphylococcus aureus gut microbiota composition in Malawian infants. In addition, the microbiota changes over time were characterized in the study infants. METHODS: Healthy 6-month-old Malawian infants were randomly assigned to 1 of 4 intervention schemes for a 6-month period. Infants in the control group were not provided with any supplementary food. Infants in other 3 groups received either micronutrient-fortified corn-soy blend, micronutrient-fortified LNS with milk protein base, or micronutrient-fortified LNS with soy protein base between 6 and 12 months of age. Fecal bifidobacteria and S aureus gut microbiota at 6 and 12 months of age were analyzed by quantitative real-time polymerase chain reaction method. RESULTS: There was no difference in change in bacterial prevalence or counts between the intervention groups during the 6-month study period. When looking at the total study population, higher counts of total bacteria (P = 0.028), Bifidobacterium genus (P = 0.027), B catenulatum (P = 0.031), and lower counts of B infantis (P < 0.001), B lactis (P < 0.001), B longum (P < 0.001), and S aureus (P < 0.001) were detected in the children's stools at 12 months rather than at 6 months of age. CONCLUSIONS: The dietary supplementation did not have an effect on the Bifidobacterium and S aureus microbiota composition of the study infants. The fecal bifidobacterial diversity of the infants, however, changed toward a more adult-like microbiota profile within the observed time. PMID- 27403609 TI - Constipation and Constipation-predominant Irritable Bowel Syndrome: A Comparative Study Using Rome III Criteria. AB - OBJECTIVE: The aim of the present study is to compare functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) in adolescents. METHODS: A school-based survey was conducted involving adolescents ages 13 to 18 years. A set of validated questionnaires including Rome III questionnaire for functional gastrointestinal disorders in children/adolescents, somatization inventory, quality of life inventory, and childhood traumatic events inventory were used for data collection. FC and IBS-C were defined using Rome III criteria. RESULTS: A total of 1792 adolescents (975 boys [45.4%]) were included in the analysis. Prevalence of FC and IBS-C were 7.7% and 1.6%, respectively. Bowel habits such as stool frequency <3 per week (10% vs 44.9%, P < 0.0001), hard stools (20% vs 40.5%, P < 0.05), painful defecation (33.3% vs 56.5%, P < 0.05), large diameter stools (23.3% vs 50.7%, P < 0.01), stool withholding behavior (20% vs 44.2%, P < 0.05), were more commonly associated with FC than did IBS-C. Occurrence of fecal incontinence (0% vs 8%, P = 0.21), urgency (56.7% vs 66.7%, P = 0.65), and straining (56.7% vs 36.9%, P = 0.47) was not significantly different between IBS-C and FC. Exposure to physical abuse, emotional abuse, and sexual abuse was equally prevalent among adolescents with FC and IBS-C. There was no difference between somatization scores, and health-related quality of life between the 2 groups. CONCLUSIONS: Although bowel habits related to stool withholding are more prevalent in FC, than in IBS-C, they are more likely to be a spectrum of a disorder rather than 2 separate entities. PMID- 27403610 TI - Liver Failure, Hepatic Siderosis, and Membrane Attack Complexes: Neonatal Hemochromatosis and/or Galactosemia?: RETRACTED. PMID- 27403611 TI - Atomic structure and oxygen deficiency of the ultrathin aluminium oxide barrier in Al/AlOx/Al Josephson junctions. AB - Al/AlOx/Al Josephson junctions are the building blocks of a wide range of superconducting quantum devices that are key elements for quantum computers, extremely sensitive magnetometers and radiation detectors. The properties of the junctions and the superconducting quantum devices are determined by the atomic structure of the tunnel barrier. The nanoscale dimension and disordered nature of the barrier oxide have been challenges for the direct experimental investigation of the atomic structure of the tunnel barrier. Here we show that the miniaturized dimension of the barrier and the interfacial interaction between crystalline Al and amorphous AlOx give rise to oxygen deficiency at the metal/oxide interfaces. In the interior of the barrier, the oxide resembles the atomic structure of bulk aluminium oxide. Atomic defects such as oxygen vacancies at the interfaces can be the origin of the two-level systems and contribute to decoherence and noise in superconducting quantum circuits. PMID- 27403612 TI - Assessment of the Accuracy of the Bethe-Salpeter (BSE/GW) Oscillator Strengths. AB - Aiming to assess the accuracy of the oscillator strengths determined at the BSE/GW level, we performed benchmark calculations using three complementary sets of molecules. In the first, we considered ~80 states in Thiel's set of compounds and compared the BSE/GW oscillator strengths to recently determined ADC(3/2) and CC3 reference values. The second set includes the oscillator strengths of the low lying states of 80 medium to large dyes for which we have determined CC2/aug-cc pVTZ values. The third set contains 30 anthraquinones for which experimental oscillator strengths are available. We find that BSE/GW accurately reproduces the trends for all series with excellent correlation coefficients to the benchmark data and generally very small errors. Indeed, for Thiel's sets, the BSE/GW values are more accurate (using CC3 references) than both CC2 and ADC(3/2) values on both absolute and relative scales. For all three sets, BSE/GW errors also tend to be nicely spread with almost equal numbers of positive and negative deviations as compared to reference values. PMID- 27403614 TI - Correlation of Histologic Subtypes and Molecular Alterations in Pulmonary Adenocarcinoma: Therapeutic and Prognostic Implications. AB - Major driver mutations of pulmonary adenocarcinomas have been identified and highlighted as actionable targets for precision cancer medicine. As phenotype is largely determined by genotype, genetic changes associated with morphologic features have recently received more attention from both pathologists and clinicians. The morphologic features of adenocarcinomas with mutations in EGFR or KRAS, or translocated ALK, have rarely been described. Pulmonary adenocarcinomas with EGFR mutations, the most common driver mutation encountered in Asian patients with pulmonary adenocarcinoma, show lepidic or papillary organotypic growth patterns. KRAS-mutated adenocarcinomas demonstrate nonorganotypic growth patterns, especially mucin-containing cells. P53 mutations are associated with aggressiveness rather than growth patterns. HER2 mutations are observed in mucinous adenocarcinoma and adenocarcinoma with micropapillary features. The histologic features of BRAF-mutated adenocarcinomas have not yet been established, but papillary, lepidic, solid, and acinar patterns have been observed. Adenocarcinomas with rearrangement of ALK, ROS1, and RET genes share similar histologic features, such as solid signet-ring cells and cribriform formation. However, adenocarcinomas with NRG1 rearrangements frequently show mucinous morphology. The histologic features and related mutations of adenocarcinomas with expression of programmed cell death-1 and programmed cell death ligands-1 may be helpful in guiding immunotherapeutic treatment. This review describes histopathologic features of adenocarcinomas and their correlation with molecular alterations. PMID- 27403613 TI - Externally calibrated parallel imaging for 3D multispectral imaging near metallic implants using broadband ultrashort echo time imaging. AB - PURPOSE: To develop an externally calibrated parallel imaging technique for three dimensional multispectral imaging (3D-MSI) in the presence of metallic implants. THEORY AND METHODS: A fast, ultrashort echo time (UTE) calibration acquisition is proposed to enable externally calibrated parallel imaging techniques near metallic implants. The proposed calibration acquisition uses a broadband radiofrequency (RF) pulse to excite the off-resonance induced by the metallic implant, fully phase-encoded imaging to prevent in-plane distortions, and UTE to capture rapidly decaying signal. The performance of the externally calibrated parallel imaging reconstructions was assessed using phantoms and in vivo examples. RESULTS: Phantom and in vivo comparisons to self-calibrated parallel imaging acquisitions show that significant reductions in acquisition times can be achieved using externally calibrated parallel imaging with comparable image quality. Acquisition time reductions are particularly large for fully phase encoded methods such as spectrally resolved fully phase-encoded three-dimensional (3D) fast spin-echo (SR-FPE), in which scan time reductions of up to 8 min were obtained. CONCLUSION: A fully phase-encoded acquisition with broadband excitation and UTE enabled externally calibrated parallel imaging for 3D-MSI, eliminating the need for repeated calibration regions at each frequency offset. Significant reductions in acquisition time can be achieved, particularly for fully phase encoded methods like SR-FPE. Magn Reson Med 77:2303-2309, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27403615 TI - Antineoplastic Treatment and Renal Injury: An Update on Renal Pathology Due to Cytotoxic and Targeted Therapies. AB - Cancer patients experience kidney injury from multiple sources, including the tumor itself, diagnostic procedures, hypovolemia, infection, and drug exposure, superimposed upon baseline chronic damage. This review will focus on cytotoxic or targeted chemotherapy-associated renal injury. In this setting, tubulointerstitial injury and thrombotic microangiopathy (vascular injury) are more common than other forms of kidney injury including glomerular. Cisplatin, pemetrexed, and ifosfamide are well-known causes of acute tubular injury/necrosis. Acute interstitial nephritis seems underrecognized in this clinical setting. Interstitial nephritis is emerging as an "immune-related adverse effect" (irAE's) with immune checkpoint inhibitors in small numbers of patients. Acute kidney injury is rarely reported with targeted therapies such as BRAF inhibitors (vemurafinib, dabrafenib), ALK inhibitors (crizotinib), and mTOR inhibitors (everolimus, temsirolimus), but additional biopsy data are needed. Tyrosine kinase inhibitors and monoclonal antibodies that block the vascular endothelial growth factor pathway are most commonly associated with thrombotic microangiopathy. Other causes of thrombotic microangiopathy in the cancer patients include cytotoxic chemotherapies such as gemcitabine and mitomycin C, hematopoietic stem cell transplant, and cancer itself (usually high-stage adenocarcinoma with marrow and vascular invasion). Cancer patients are historically underbiopsied, but biopsy can reveal type, acuity, and chronicity of renal injury, and facilitate decisions concerning continuation of chemotherapy and/or initiation of renoprotective therapy. Biopsy may also reveal unrelated and unanticipated findings in need of treatment. PMID- 27403616 TI - Strong and Anomalous Thermal Expansion Precedes the Thermosalient Effect in Dynamic Molecular Crystals. AB - The ability of thermosalient solids, organic analogues of inorganic martensites, to move by rapid mechanical reconfiguration or ballistic event remains visually appealing and potentially useful, yet mechanistically elusive phenomenon. Here, with a material that undergoes both thermosalient and non-thermosalient phase transitions, we demonstrate that the thermosalient effect is preceded by anomalous thermal expansion of the unit cell. The crystal explosion occurs as sudden release of the latent strain accumulated during the anisotropic, exceedingly strong expansion of the unit cell with alphaa = 225.9 * 10(-6) K(-1), alphab = 238.8 * 10(-6) K(-1) and alphac = -290.0 * 10(-6) K(-1), the latter being the largest negative thermal expansivity observed for an organic compound thus far. The results point out to the occurence of the thermosalient effect in phase transitions as means to identify new molecular materials with strong positive and/or negative thermal expansion which prior to this work could only be discovered serendipitously. PMID- 27403617 TI - The Efficacy and the Safety of Prophylactic N-Butyl-2-Cyanoacrylate Injection for Gastric Varices Using a Modified Injection Technique. AB - BACKGROUND: Primary prophylactic N-butyl-2-cyanoacrylate (NBC) injection for nonbleeding gastric varices (GVs) remains controversial. In addition, there is still no consensus concerning the technique, its safety, and long-term results. AIM: To analyze the safety and the efficacy of NBC for primary prophylaxis of GVs using a modified injection technique. METHODS: Between February 2004 and June 2014, a total of 72 patients with GVs with a high risk of bleeding, who received undiluted NBC injection using a modified "sandwich" method for primary prophylaxis in General Hospital of Chengdu Military Command, were enrolled in this retrospective study. All patients were followed up at 1 to 2 weeks, 3 months, 6 months, and thereafter every 6 months or whenever required, using endoscope detection. The rate of obliteration, bleeding, recurrence, and complications was evaluated. RESULTS: According to the standard Sarin classification, 28 patients were IGV1 and 44 patients were GEV2. Hepatitis B virus infection was the major cause of portal hypertension. The mean number of sessions were 1.4 (1 to 3) and the mean volume of NBC per session was 3.5 mL (1 to 6 mL). One injection per session was used in 41 patients (56.9%) and 2 or more injections were used in the remaining 31 patients (43.1%). During the follow-up (27 mo; range, 12 to 67 mo), complete obliteration of GVs was achieved in 93.1% of the patients (67/72). One session of NBC injection was enough to obliterate GVs in 49 patients (68.1%), and 2 or more sessions were needed in 23 patients (31.9%). In addition, the bleeding and the recurrence rate were 11.1% (8/72) and 15.3% (11/72), respectively, during the follow-up. The cumulative bleeding-free rate at 1, 3, and 5 years was 95.8%, 91.7%, and 88.9%, respectively. Worsening of esophageal varices was observed in 13 patients (9 in GEV2 and 4 in IGV1). No serious complications, such as distal embolism, were observed in all patients. CONCLUSIONS: Prophylactic endoscopic NBC injection using a modified injection technique may be a safe and effective treatment for gastric fundal varices with a high risk of bleeding. PMID- 27403618 TI - The Role of Laparoscopy in the Treatment of Anastomotic Leaks After Minimally Invasive Colorectal Resections for Cancer. AB - AIM OF THE STUDY: The aim of this study was to describe the role of laparoscopy in the treatment of leaks occurring after minimally invasive colorectal resections. MATERIALS AND METHODS: Thirty-four of 566 consecutive patients who underwent minimally invasive colorectal resection for cancer between January 2004 and December 2012 and who showed signs of anastomotic leakage (6%) requiring reoperation were studied using a prospectively maintained database. Patient characteristics, clinical signs, the surgical approach, the role of laparoscopy, operative and postoperative results, and the rate of permanent stoma were analyzed. RESULTS: The median time to diagnosis of an anastomotic leak after surgery was 5.5 days. The median time to reoperation from the diagnosis of leakage was 2 days. Leaks were treated laparoscopically in 21 of 34 (61.8%) patients. Anastomoses were dismantled in 14 patients (41.2%) and the procedure was performed laparoscopically in 28.6% of the cases. The postoperative morbidity was 55.9%, the perioperative mortality 5.7%, and the rate of permanent stoma was 8.8%. CONCLUSIONS: Laparoscopic reoperation can be performed in most cases of anastomotic leaks occurring after minimally invasive colorectal resection for cancer. Anastomosis can be dismantled laparoscopically in 28.6% of the cases. A permanent stoma was necessary only in patients with terminal stomas. PMID- 27403619 TI - Effectiveness of Laparoscopic Surgery for Obstructive Colorectal Cancer After Tube Decompression. AB - BACKGROUND: It is debatable whether laparoscopic surgery is suitable for obstructive colorectal cancer. MATERIALS AND METHODS: We retrospectively reviewed the clinical and oncological effectiveness of laparoscopic surgery after tube decompression for obstructive colorectal cancer in 54 patients (18 laparoscopic resections, 36 open resections). RESULTS: There were no significant differences between groups with respect to mean size, location, depth, and stage of tumor, median operating times, or median number of lymph nodes retrieved. Abdominal wound infection rate was significantly lower in the laparoscopic than in the open group (0%:22%, P=0.02), as were mean times to first gas passage after surgery (2.3:3.4 d, P=0.002) and mean postoperative hospital stays (16:24.3 d, P=0.03). The 3-year disease-free survival rate of curative resection cases in the laparoscopic (85%) and open (72%) groups were not significantly different. CONCLUSIONS: Laparoscopic surgery after tube decompression achieves faster recovery and equal oncological outcome as open surgery and should be a treatment of choice for obstructive colorectal cancer. PMID- 27403620 TI - Laparoscopic Surgery in Nonparasitic Cysts of the Liver: Results Observed in a Series of Consecutive Cases. AB - The purpose of this study was to report the results of laparoscopic treatment of nonparasitic cysts of the liver (NPCL) in terms of postoperative morbidity (POM) and recurrence. Prospective case series of patients operated on for NPCL at the Clinica Mayor in Temuco, Chile (2008 to 2015). The preoperative study consisted of general examinations, abdominal ultrasound or computed tomographic scan. The outcome variable was POM. Other variables of interest were surgical time, need for conversion, hospital stay, mortality, and recurrence. In the study period, 41 patients with NPCL underwent surgery. Median age of the series was 58 years, and 75.6% of the cases were female. The median ultrasound diameter of the lesions was 10 cm and surgical time was 50 minutes. All patients underwent a cystectomy. There was no conversion, no record of POM, mortality or recurrence. The treatment applied in this series of NPCL is associated with an adequate postoperative evolution. PMID- 27403621 TI - Comparison of Short-term Outcomes After Laparoscopic Versus Open Hartmann Reversal: A Case-matched Study. AB - PURPOSE: The aim of this study is to compare short-term outcomes of laparoscopic versus open Hartmann reversal. MATERIALS AND METHODS: Patients who underwent Hartmann reversal between January 2005 and September 2014 were identified and matched for age, sex, body mass index, American Society of Anesthesiologists score, and creation of diverting ileostomy to open counterparts. Patient characteristics and postoperative outcomes (30 d) were evaluated. RESULTS: Eighteen patients with laparoscopic Hartmann reversal were matched to 18 open patients. There were no differences between laparoscopic versus open groups in terms of operative time (157.7+/-52.2 vs. 151.5+/-49.3 min, P>0.05) or overall complication rates [6 (33.3%) vs. 6 (33.3%) (P>0.05)]. No anastomotic leaks or mortality occurred in either group. However, the laparoscopic group was associated with significantly decreased estimated blood loss (114+/-103 vs. 217+/ 125 mL, P<0.05), faster return of bowel function (3.2+/-0.6 vs. 4+/-0.6 d, P<0.05), and reduced hospital stay (5.4+/-3.1 vs. 8.3+/-4.8 d, P<0.05). CONCLUSIONS: Laparoscopic Hartmann reversal can be safely performed with better short-term outcomes in carefully selected patients. PMID- 27403622 TI - The Role of Crowdsourcing in Assessing Surgical Skills. AB - BACKGROUND: Assessing surgical skill is critical in improving patient care while reducing medical errors, length of stay, and readmission rates. Crowdsourcing provides 1 potential method for accurately assessing this; only recently has crowdsourcing been studied as a valid way to provide feedback to surgeons. The results of such studies are explored. DATA SOURCES: A systematic literature search was performed on PubMed to identify studies that have attempted to validate crowdsourcing as a method for assessing surgical skill. Through a combination of abstract screening and full-length review, 9 studies that met the inclusion criteria were reviewed. CONCLUSIONS: Crowdsourcing has been validated as an important way to provide feedback for surgical skill. It has been demonstrated to be effective in both dry-lab and live surgery, for a variety of tasks and methods. However, more studies must be performed to ensure that crowdsourcing can provide quality feedback in a wider variety of scenarios. PMID- 27403623 TI - Transthyretin familial amyloid polyneuropathy (TTR-FAP) in Mallorca: a comparison between late- and early-onset disease. AB - The age of onset (AO) of hereditary ATTR amyloidosis (hATTR) is known to vary between populations, with differing characteristics reported according to AO in endemic/non-endemic foci. This was a retrospective study of patients with early AO (<50 years) and late AO (>=50 years) hATTR at our center in Mallorca. Data were collected on patient demographics, clinical disease manifestation, and physical symptoms. A total of 95 patients were analyzed, with mean follow-up of 9 years from diagnosis. The early AO group included 53 patients (33 male) and the late AO group included 42 patients (21 male). Neurologic involvement was the most common initial symptom, although it was significantly more frequent in the late AO vs. early AO group (p = 0.015). Autonomic involvement was observed in 26% of patients in the early AO group, but was rarely observed in the late AO group (5%). During follow up, cardiologic symptoms, renal involvement, and ophthalmologic symptoms were significantly more common in the late AO group (p < 0.05). This retrospective study demonstrates the variation in disease presentation and progression according to AO of hATTR at our Mallorcan center. PMID- 27403624 TI - Wild immunology assessed by multidimensional mass cytometry. AB - A great part of our knowledge on mammalian immunology has been established in laboratory settings. The use of inbred mouse strains enabled controlled studies of immune cell and molecule functions in defined settings. These studies were usually performed in specific-pathogen free (SPF) environments providing standardized conditions. In contrast, mammalians including humans living in their natural habitat are continuously facing pathogen encounters throughout their life. The influences of environmental conditions on the signatures of the immune system and on experimental outcomes are yet not well defined. Thus, the transferability of results obtained in current experimental systems to the physiological human situation has always been a matter of debate. Studies elucidating the diversity of "wild immunology" imprintings in detail and comparing it with those of "clean" lab mice are sparse. Here, we applied multidimensional mass cytometry to dissect phenotypic and functional differences between distinct groups of laboratory and pet shop mice as a source for "wild mice". For this purpose, we developed a 31-antibody panel for murine leukocyte subsets identification and a 35-antibody panel assessing various cytokines. Established murine leukocyte populations were easily identified and diverse immune signatures indicative of numerous pathogen encounters were classified particularly in pet shop mice and to a lesser extent in quarantine and non-SPF mice as compared to SPF mice. In addition, unsupervised analysis identified distinct clusters that associated strongly with the degree of pathogenic priming, including increased frequencies of activated NK cells and antigen-experienced B- and T-cell subsets. Our study unravels the complexity of immune signatures altered under physiological pathogen challenges and highlights the importance of carefully adapting laboratory settings for immunological studies in mice, including drug and therapy testing. (c) 2016 International Society for Advancement of Cytometry. PMID- 27403625 TI - A Simple Preparation of Photoactive Glass Surfaces Allowing Coatings via the "Grafting-from" Method. AB - A simple and straightforward synthesis was developed to prepare the siloxy substituted bis(acylphosphane)oxide 4-(trimethoxysilyl)butyl-3-[bis(2,4,6 trimethylbenzoyl)phosphinoyl]-2-methyl-propionate TMESI(2)-BAPO. This new photoinitiator was successfully fixed to glass surfaces. Subsequent irradiation with UV light in the presence of either a partially fluorinated acrylate or a specifically synthesized polysiloxane containing polymerizable acrylate functions allowed the generation of polymer chains which grew from the surface in an efficient radical polymerization process ("grafting-from" procedure). Durable hydrophobic surfaces were prepared which have contact angles between 93 degrees and 95 degrees . The silanization process with the photoinitiator and the grafting process were followed and analyzed with various techniques including high-resolution X-ray photoelectron spectroscopy. PMID- 27403627 TI - Biopharmaceuticals and gene vectors opening new avenues in cancer immune therapy. PMID- 27403626 TI - Breastfeeding Duration and Anogenital Distance in 2-Year-Old Infants. AB - BACKGROUND: The anogenital distance (AGD) is an anthropometric marker determined by exposures to androgens in utero and throughout the first few months of life. Early exposures to endocrine-disrupting chemicals such as phthalates have been significantly associated with shortened AGD in boys. Limited studies have explored phthalate concentrations in breast milk and infant formula. OBJECTIVE: To explore the associations between breastfeeding duration and AGD measures in infants. MATERIALS AND METHODS: MALAMA (Medio Ambiente y Lactancia Materna) is a follow-up study of 430 mother-child pairs, from birth to 2 years, from two population-based cohorts in Murcia, Spain. Data were collected through medical visits and telephone surveys from birth to 2 years of age. World Health Organization breastfeeding definitions were used. AGD measurements were assessed in a subsample of 71 boys and 49 girls at the 2-year visit. Descriptive analyses, Pearson correlations, and linear regressions were calculated between AGD and breastfeeding duration. RESULTS: Duration of all types of breastfeeding, especially full breastfeeding (FB), is correlated with AGD measures in boys (p < 0.05). AGDAS (anoscrotal distance) and AGDAP (anopenile distance) were positively associated with FB (beta = 0.004, 95%CI: 0.001-0.007 and beta = 0.003, 95%CI: 0.000-0.007, respectively). CONCLUSIONS: A positive correlation between AGD in male infants and the duration of breastfeeding is reported. Inversely, early introduction of infant formula could lead to the reduction of AGD in boys. PMID- 27403628 TI - Design and evaluation of buccal-adhesive system made of modified xanthan. AB - BACKGROUND: Introducing the concept of mucoadhesion in the 1980s, application of mucoadhesive polymers for buccal drug delivery has been the subject of pharmaceutical interest. AIM: The purpose of this study was to modify well-known xanthan in order to remarkably boost its suitability for buccal adhesiveness. METHOD: Xanthan (X) was chemically modified by covalent binding of L-cysteine (SH) exhibiting sulfhydryl groups on the polymeric backbone via amide bond formation. Cytotoxicity, stability properties and mucoadhesiveness, respectively, of sulfhydryl-modified xanthan (H-SH) was investigated compared with unmodified xanthan (X). RESULTS: According to cell viability studies X-SH was safe to use. X SH revealed 1.61-fold higher stability in comparison to unmodified xanthan. Thereafter, mucoadhesion of X-SH augmented 8.35-fold in case of rotating cylinder assay. Tensile study showed 2.65-fold higher total work of adhesion when comparing X-SH with X. CONCLUSION: In completion, novel sulfhydryl-modified xanthan proved itself being a useful and promising excipient for buccal-adhesive delivery systems. PMID- 27403629 TI - Nanomedicine therapeutics and diagnostics are the goal. AB - Understanding and exploiting molecular mechanisms in biology is central to chemical biology. In 20 years, chemical biology research has advanced from simple mechanistic studies using isolated biological macromolecules to molecular-level and nanomolecular-level mechanistic studies involving whole organisms. This review documents the best of my personal and collaborative academic research work that has made use of a solid organic chemistry and chemical biology approach toward nanomedicine, in which my focus has been on the design, creation and use of synthetic, self-assembly lipid-based nanoparticle technologies for the functional delivery of active pharmaceutical ingredients to target cells in vivo. This research is now leading to precision therapeutics approaches (PTAs) for the treatment of diseases that may define the future of nanomedicine. PMID- 27403630 TI - Delivering therapy to target: improving the odds for successful drug development. AB - The direct delivery of drugs and other agents into tissue (in contrast to systemic administration) has been used in clinical trials for brain cancer, neurodegenerative diseases and peripheral tumors. However, continuing evidence suggests that clinical efficacy depends on adequate delivery to a target. Inadequate delivery may have doomed otherwise effective drugs, through failure to distinguish drug inefficacy from poor distribution at the target. Conventional pretreatment clinical images of the patient fail to reveal the complexity and diversity of drug transport pathways in tissue. We discuss the richness of these pathways and argue that development and patient treatment can be sped up and improved by: using quantitative as well as 'real-time' imaging; customized simulations using data from that imaging; and device designs that optimize the drug-device combination. PMID- 27403631 TI - Delivering therapeutics in peripheral artery disease: challenges and future perspectives. AB - Targeted and sustained delivery of biologicals to improve neovascularization has been focused on stimulation angiogenesis. The formation of collaterals however is hemodynamically much more efficient, but as a target of therapy has been under utilized. Although there is good understanding of the molecular processes involving collateral formation and there are interesting drugable candidates, the need for targeting and sustained delivery is still an obstacle towards safe and effective treatment. Molecular targeting with nanoparticles of liposomes is promising and so are peri-vascularly delivered polymer-based protein reservoirs. These developments will lead to future arteriogenesis strategies that are adjunct to current revascularization. PMID- 27403632 TI - Challenges in nasal drug absorption: how far have we come? AB - The nasal route is commonly used for local delivery of drugs to treat inflammatory conditions. It is also an attractive route for systemic delivery of some drugs. Irrespective of intended use, administered drugs must permeate the epithelial or olfactory membrane to be effective. The enthusiasm for potential use of the nasal route for systemic drug delivery has not been met by comparable success. In this paper, the anatomical and physiological attributes of the nasal cavity and paranasal sinuses important for drug delivery and challenges limiting drug absorption are discussed. Efforts made so far in improving nasal drug absorption such as overcoming restrictive nasal geometry and paranasal sinuses accessibility, mucociliary clearance, absorption barriers, metabolism and drug physicochemical challenges are discussed. Highlights on future prospects of nasal drug delivery/absorption were discussed. PMID- 27403633 TI - Corrigendum. PMID- 27403634 TI - Localized spatially nonlinear matter waves in atomic-molecular Bose-Einstein condensates with space-modulated nonlinearity. AB - The intrinsic nonlinearity is the most remarkable characteristic of the Bose Einstein condensates (BECs) systems. Many studies have been done on atomic BECs with time- and space- modulated nonlinearities, while there is few work considering the atomic-molecular BECs with space-modulated nonlinearities. Here, we obtain two kinds of Jacobi elliptic solutions and a family of rational solutions of the atomic-molecular BECs with trapping potential and space modulated nonlinearity and consider the effect of three-body interaction on the localized matter wave solutions. The topological properties of the localized nonlinear matter wave for no coupling are analysed: the parity of nonlinear matter wave functions depends only on the principal quantum number n, and the numbers of the density packets for each quantum state depend on both the principal quantum number n and the secondary quantum number l. When the coupling is not zero, the localized nonlinear matter waves given by the rational function, their topological properties are independent of the principal quantum number n, only depend on the secondary quantum number l. The Raman detuning and the chemical potential can change the number and the shape of the density packets. The stability of the Jacobi elliptic solutions depends on the principal quantum number n, while the stability of the rational solutions depends on the chemical potential and Raman detuning. PMID- 27403635 TI - American Indian elders share personal stories of alcohol use with younger tribal members. AB - In this Great Lakes Indian reservation qualitative study we utilized focus groups in the form of talking circles to elicit tribal members' views of alcohol use. We report on how the elder participants utilized the talking circles to inform the youth of the deleterious effects of alcohol use and abuse. Indigenous research methods were utilized so elder tribal members were consulted about the study; an elder was hired as a research associate; youth were hired as note takers/observers; and the 2-hour groups were led by a tribal community member. Demographic data were gathered, and a semistructured guide with substance use questions was utilized. Tribal members, 30 females and 19 males, age 12 to 78 participated in 8 talking circles (N = 49). Tribal elders unexpectedly utilized the format as an opportunity for cross-generational storytelling to convey their own oral histories of the harmful effects of alcohol use for the younger participants. They shared personal pathways to quitting or to a reduction in drinking with messages aimed at preventing the youth from initiating drinking. A shortage of American Indian (AI) substance abuse treatment programs that are culturally relevant exists. The widespread and renewed use of cross-generational talking circles could serve as an inexpensive substance abuse prevention and intervention treatment modality for AI youth. The elders' stories highlight the need to rejuvenate traditional methods of healing among AIs to reduce the initiation and/or harmful effects of overuse of alcohol among AI youth. PMID- 27403636 TI - Characterization of a Crosslinked Elastomeric-Protein Inspired Polypeptide. AB - Materials inspired by natural proteins have a great appeal in tissue engineering for their biocompatibility and similarity to extracellular matrix (ECM). Chimeric polypeptides inspired by elastomeric proteins such as silk, elastin, and collagen are of outstanding interest in the field. A recombinant polypeptide constituted of three different blocks, each of them having sequences derived from elastin, resilin, and collagen proteins, was demonstrated to be a good candidate as biomaterial for its self-assembling characteristics and biocompatibility. Herein, taking advantage of the primary amine functionalities present in the linear polypeptide, we crosslinked it with 1,6-hexamethylene-diisocyanate (HMDI). The characterization of the obtained polypeptide was realized by CD spectroscopy, AFM, and SEM microscopies. The obtained results, although not conclusive, demonstrate that the crosslinked polypeptide gave rise to porous networks, thin nanowires, and films not observable for the linear polypeptide. Chirality 28:606 611, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27403637 TI - Catalytic Carbocation Generation Enabled by the Mesolytic Cleavage of Alkoxyamine Radical Cations. AB - A new catalytic method is described to access carbocation intermediates via the mesolytic cleavage of alkoxyamine radical cations. In this process, electron transfer between an excited state oxidant and a TEMPO-derived alkoxyamine substrate gives rise to a radical cation with a remarkably weak C-O bond. Spontaneous scission results in the formation of the stable nitroxyl radical TEMPO(.) as well as a reactive carbocation intermediate that can be intercepted by a wide range of nucleophiles. Notably, this process occurs under neutral conditions and at comparatively mild potentials, enabling catalytic cation generation in the presence of both acid sensitive and easily oxidized nucleophilic partners. PMID- 27403638 TI - Atomic-scale Studies of Uranium Oxidation and Corrosion by Water Vapour. AB - Understanding the corrosion of uranium is important for its safe, long-term storage. Uranium metal corrodes rapidly in air, but the exact mechanism remains subject to debate. Atom Probe Tomography was used to investigate the surface microstructure of metallic depleted uranium specimens following polishing and exposure to moist air. A complex, corrugated metal-oxide interface was observed, with approximately 60 at.% oxygen content within the oxide. Interestingly, a very thin (~5 nm) interfacial layer of uranium hydride was observed at the oxide-metal interface. Exposure to deuterated water vapour produced an equivalent deuteride signal at the metal-oxide interface, confirming the hydride as originating via the water vapour oxidation mechanism. Hydroxide ions were detected uniformly throughout the oxide, yet showed reduced prominence at the metal interface. These results support a proposed mechanism for the oxidation of uranium in water vapour environments where the transport of hydroxyl species and the formation of hydride are key to understanding the observed behaviour. PMID- 27403639 TI - In-vivo multispectral video endoscopy towards in-vivo hyperspectral video endoscopy. AB - For in-vivo diagnostics of cancer and pre-cancer in the stomach, there is no endoscopic procedure offering both high sensitivity and high specificity. Our data suggest that multispectral or hyperspectral imaging may be helpful to solve this problem. It is successfully applied to the detection and analysis of easily reachable carcinomas, ex-vivo samples of hollow organ mucosal carcinomas and also histological samples. An endoscopy system which allows flexible multispectral videoendoscopy for in-vivo diagnostics has so far been unavailable. To overcome this problem, we modified a standard Olympus endoscopy system to conduct in-vivo multispectral imaging of the upper GI tract. The pilot study is performed on 14 patients with adeno carcinomas in the stomach. For analysis, Support Vector Machine with linear and Gaussian Kernel, AdaBoost, RobustBoost and Random-Forest walk are used and compared for the data classification with a leave-one-out strategy. The margin of the carcinoma for the training of the classifier is drawn by expert-labeling. The cancer findings are cross-checked by biopsies. We expect that the present study will help to improve the further development of hyperspectral endoscopy and to overcome some of the problems to be faced in this process. PMID- 27403640 TI - Functional Complementation Analysis (FCA): A Laboratory Exercise Designed and Implemented to Supplement the Teaching of Biochemical Pathways. AB - Functional complementation assay (FCA) is an in vivo assay that is widely used to elucidate the function/role of genes/enzymes. This technique is very common in biochemistry, genetics and many other disciplines. A comprehensive overview of the technique to supplement the teaching of biochemical pathways pertaining to amino acids, peptidoglycan and the bacterial stringent response is reported in this manuscript. Two cDNAs from the model plant organism Arabidopsis thaliana that are involved in the metabolism of lysine (L,L-diaminopimelate aminotransferase (dapL) and tyrosine aminotransferase (tyrB) involved in the metabolism of tyrosine and phenylalanine are highlighted. In addition, the bacterial peptidoglycan anabolic pathway is highlighted through the analysis of the UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-meso-2,6-diaminopimelate ligase (murE) gene from the bacterium Verrucomicrobium spinosum involved in the cross linking of peptidoglycan. The bacterial stringent response is also reported through the analysis of the rsh (relA/spoT homolog) bifunctional gene responsible for a hyper-mucoid phenotype in the bacterium Novosphingobium sp. Four examples of FCA are presented. The video will focus on three of them, namely lysine, peptidoglycan and the stringent response. PMID- 27403641 TI - Wave mode extraction from multimodal wave signals in an orthotropic composite plate. AB - In this paper the post-processing procedure based on the mode orthogonality is applied to extract individual waveforms at a composite plate edge from multimodal signals. To obtain the amplitudes of individual modes, numerically predicted modal through-thickness stress and displacement field values are used in the orthogonality relation. The performance of the mode extraction technique is evaluated by processing signals obtained from Finite Element (FE) modeling and experimental measurements. The propagation of the overlapping wave packets of Lamb modes S0 and A0 is considered along the fiber direction and perpendicular to that direction. The required experimental two-dimensional displacement components at the plate edge are measured by 3D Scanning Laser Doppler Vibrometer (3D SLDV). It is demonstrated that S0 mode can be extracted very well from the signal but A0 mode with slightly poorer accordance with the original waveforms and numerical predictions. PMID- 27403642 TI - Optimization of contrast resolution by genetic algorithm in ultrasound tissue harmonic imaging. AB - The development of ultrasound imaging techniques such as pulse inversion has improved tissue harmonic imaging. Nevertheless, no recommendation has been made to date for the design of the waveform transmitted through the medium being explored. Our aim was therefore to find automatically the optimal "imaging" wave which maximized the contrast resolution without a priori information. To overcome assumption regarding the waveform, a genetic algorithm investigated the medium thanks to the transmission of stochastic "explorer" waves. Moreover, these stochastic signals could be constrained by the type of generator available (bipolar or arbitrary). To implement it, we changed the current pulse inversion imaging system by including feedback. Thus the method optimized the contrast resolution by adaptively selecting the samples of the excitation. In simulation, we benchmarked the contrast effectiveness of the best found transmitted stochastic commands and the usual fixed-frequency command. The optimization method converged quickly after around 300 iterations in the same optimal area. These results were confirmed experimentally. In the experimental case, the contrast resolution measured on a radiofrequency line could be improved by 6% with a bipolar generator and it could still increase by 15% with an arbitrary waveform generator. PMID- 27403643 TI - A numerical study of non-collinear wave mixing and generated resonant components. AB - Interaction of two non-collinear nonlinear ultrasonic waves in an elastic half space with quadratic nonlinearity is investigated in this paper. A hyperbolic system of conservation laws is applied here and a semi-discrete central scheme is used to solve the numerical problem. The numerical results validate that the model can be used as an effective method to generate and evaluate a resonant wave when two primary waves mix together under certain resonant conditions. Features of the resonant wave are analyzed both in the time and frequency domains, and variation trends of the resonant waves together with second harmonics along the propagation path are analyzed. Applied with the pulse-inversion technique, components of resonant waves and second harmonics can be independently extracted and observed without distinguishing times of flight. The results show that under the circumstance of non-collinear wave mixing, both sum and difference resonant components can be clearly obtained especially in the tangential direction of their propagation. For several rays of observation points around the interaction zone, the further it is away from the excitation sources, generally the earlier the maximum of amplitude arises. From the parametric analysis of the phased array, it is found that both the length of array and the density of element have impact on the maximum of amplitude of the resonant waves. The spatial distribution of resonant waves will provide necessary information for the related experiments. PMID- 27403644 TI - Tandem mass spectral libraries of peptides and their roles in proteomics research. AB - Proteomics is a rapidly maturing field aimed at the high-throughput identification and quantification of all proteins in a biological system. The cornerstone of proteomic technology is tandem mass spectrometry of peptides resulting from the digestion of protein mixtures. The fragmentation pattern of each peptide ion is captured in its tandem mass spectrum, which enables its identification and acts as a fingerprint for the peptide. Spectral libraries are simply searchable collections of these fingerprints, which have taken on an increasingly prominent role in proteomic data analysis. This review describes the historical development of spectral libraries in proteomics, details the computational procedures behind library building and searching, surveys the current applications of spectral libraries, and discusses the outstanding challenges. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:634-648, 2017. PMID- 27403645 TI - One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin. AB - AIMS: Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis. MATERIALS AND METHODS: Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on. RESULTS: The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (<=1.5 kg) occurred in both groups. Similar proportions of patients reported >=1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (<=2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on. CONCLUSIONS: Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia. PMID- 27403646 TI - Alternative Method of Removing Otoliths from Sturgeon. AB - Extracting the otoliths (ear bones) from fish that have very thick skulls can be difficult and very time consuming. The common practice of making a transverse vertical incision on the top of the skull with a hand or electrical saw may damage the otolith if not performed correctly. Sturgeons (Acipenseridae) are one family in particular that have a very large and thick skull. A new laboratory method entering the brain cavity from the ventral side of the fish to expose the otoliths was easier than other otolith extraction methods found in the literature. Methods reviewed in the literature are designed for the field and are more efficient at processing large quantities of fish quickly. However, this new technique was designed to be more suited for a laboratory setting when time is not pressing and successful extraction from each specimen is critical. The success of finding and removing otoliths using this technique is very high and does not compromise the structure in any manner. This alternative technique is applicable to other similar fish species for extracting the otoliths. PMID- 27403647 TI - Electrophysiological Method for Recording Intracellular Voltage Responses of Drosophila Photoreceptors and Interneurons to Light Stimuli In Vivo. AB - Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method described here enables the investigator to measure long-lasting (from minutes to hours) high-quality intracellular responses from single Drosophila R1-R6 photoreceptors and Large Monopolar Cells (LMCs) to light stimuli. Because the recording system has low noise, it can be used to study variability among individual cells in the fly eye, and how their outputs reflect the physical properties of the visual environment. We outline all key steps in performing this technique. The basic steps in constructing an appropriate electrophysiology set-up for recording, such as design and selection of the experimental equipment are described. We also explain how to prepare for recording by making appropriate (sharp) recording and (blunt) reference electrodes. Details are given on how to fix an intact fly in a bespoke fly-holder, prepare a small window in its eye and insert a recording electrode through this hole with minimal damage. We explain how to localize the center of a cell's receptive field, dark- or light-adapt the studied cell, and to record its voltage responses to dynamic light stimuli. Finally, we describe the criteria for stable normal recordings, show characteristic high-quality voltage responses of individual cells to different light stimuli, and briefly define how to quantify their signaling performance. Many aspects of the method are technically challenging and require practice and patience to master. But once learned and optimized for the investigator's experimental objectives, it grants outstanding in vivo neurophysiological data. PMID- 27403648 TI - Intravital Imaging of Neutrophil Priming Using IL-1beta Promoter-driven DsRed Reporter Mice. AB - Neutrophils are the most abundant leukocytes in human blood circulation and are quickly recruited to inflammatory sites. Priming is a critical event that enhances the phagocytic functionality of neutrophils. Although extensive studies have unveiled the existence and importance of neutrophil priming during infection and injury, means of visualizing this process in vivo have been unavailable. The protocol provided enables monitoring of the dynamic process of neutrophil priming in living animals by combining three methodologies: 1) DsRed reporter signal - used as a measure of priming 2) in vivo neutrophil labeling - achieved by injection of fluorescence-conjugated anti-lymphocyte antigen 6G (Ly6G) monoclonal antibody (mAb) and 3) intravital confocal imaging. Several critical steps are involved in this protocol: oxazolone-induced mouse ear skin inflammation, appropriate sedation of animals, repeated injections of anti-Ly6G mAb, and prevention of focus drift during imaging. Although a few limitations have been observed, such as the limit of continuous imaging time (~ 8 hr) in one mouse and the leakage of fluorescein isothiocyanate-dextran from blood vessels in the inflammatory state, this protocol provides a fundamental framework for intravital imaging of primed neutrophil behavior and function, which can easily be expanded to examination of other immune cells in mouse inflammation models. PMID- 27403649 TI - Preparation of Biopolymer Aerogels Using Green Solvents. AB - Although the first reports on aerogels made by Kistler(1) in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers (gelatin, agar, cellulose), only recently have biomasses been recognized as an abundant source of chemically diverse macromolecules for functional aerogel materials. Biopolymer aerogels (pectin, alginate, chitosan, cellulose, etc.) exhibit both specific inheritable functions of starting biopolymers and distinctive features of aerogels (80-99% porosity and specific surface up to 800 m(2)/g). This synergy of properties makes biopolymer aerogels promising candidates for a wide gamut of applications such as thermal insulation, tissue engineering and regenerative medicine, drug delivery systems, functional foods, catalysts, adsorbents and sensors. This work demonstrates the use of pressurized carbon dioxide (5 MPa) for the ionic cross linking of amidated pectin into hydrogels. Initially a biopolymer/salt dispersion is prepared in water. Under pressurized CO2 conditions, the pH of the biopolymer solution is lowered to 3 which releases the crosslinking cations from the salt to bind with the biopolymer yielding hydrogels. Solvent exchange to ethanol and further supercritical CO2 drying (10 - 12 MPa) yield aerogels. Obtained aerogels are ultra-porous with low density (as low as 0.02 g/cm(3)), high specific surface area (350 - 500 m(2)/g) and pore volume (3 - 7 cm(3)/g for pore sizes less than 150 nm). PMID- 27403650 TI - Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles. AB - The cyclopenta[b]indole motif is present in several natural and synthetic biologically active compounds, being directly responsible for the biological effects some of them present. We described herein a three step sequence for the synthesis of cyclopenta[b]indoles with a great structural diversity. The method is based on an oxidative Michael addition of suitable indoles on the double bond of Morita-Baylis-Hillman adducts mediated by a hypervalent iodine reagent (IBX) to form beta-ketoesters, which were chemoselectively reduced with NaBH4 in THF to give the corresponding beta-hydroxy-esters. The diastereoisomeric mixture was then treated with a catalytic amount of triflic acid (20 mol %) to give cyclopenta[b]indoles with overall yields ranging from 8 to 73% (for 2 steps). The acid-catalyzed cyclization step gave the required heterocycles, via an intramolecular Friedel-Crafts reaction, with high diastereoselectivity, where only the trans product was observed. A mechanistic study monitored by ESI-(+)-MS was also conducted to collect evidence about the mechanism of this reaction. The new molecules herein synthesized were also evaluated against a panel of human cancer cells demonstrating a promising antitumoral profile. PMID- 27403651 TI - Field Demonstration of a Multiplexed Point-of-Care Diagnostic Platform for Plant Pathogens. AB - Effective disease management strategies to prevent catastrophic crop losses require rapid, sensitive, and multiplexed detection methods for timely decision making. To address this need, a rapid, highly specific and sensitive point-of care method for multiplex detection of plant pathogens was developed by taking advantage of surface-enhanced Raman scattering (SERS) labeled nanotags and recombinase polymerase amplification (RPA), which is a rapid isothermal amplification method with high specificity. In this study, three agriculturally important plant pathogens (Botrytis cinerea, Pseudomonas syringae, and Fusarium oxysporum) were used to demonstrate potential translation into the field. The RPA SERS method was faster, more sensitive than polymerase chain reaction, and could detect as little as 2 copies of B. cinerea DNA. Furthermore, multiplex detection of the three pathogens was demonstrated for complex systems such as the Arabidopsis thaliana plant and commercial tomato crops. To demonstrate the potential for on-site field applications, a rapid single-tube RPA/SERS assay was further developed and successfully performed for a specific target outside of a laboratory setting. PMID- 27403652 TI - A Highly Selective and Sensitive Fluorescence Detection Method of Glyphosate Based on an Immune Reaction Strategy of Carbon Dot Labeled Antibody and Antigen Magnetic Beads. AB - A sensitive fluorescence detection method for glyphosate (GLY) was established based on immune reaction. First, carbon dot labeled antibodies (lgG-CDs) which were able to specifically identify glyphosate were prepared with the environmentally friendly carbon dots (CDs) and glyphosate antibody (lgG). lgG-CDs could be used to in situ visualize the distribution of glyphosate in plant tissues. In order to eliminate the effects of excess lgG-CDs on the determination of GLY, antigen magnetic beads Fe3O4-GLY based on magnetic nanoparticles Fe3O4 and glyphosate were constructed and utilized to couple with the excess lgG-CDs. After magnetic separation to remove antigen magnetic beads, there was a linear relationship between the fluorescence intensity of lgG-CDs and the logarithmic concentration of glyphosate in the range of 0.01-80 MUg/mL with a detection limit of 8 ng/mL. The method was used for the detection of glyphosate in Pearl River water, tea, and soil samples with satisfactory recovery ratio between 87.4% and 103.7%. PMID- 27403653 TI - Inhibition of Fibrillar Assemblies of l-Phenylalanine by Crown Ethers: A Potential Approach toward Phenylketonuria. AB - In this article, our aim is to investigate the interaction of l-phenylalanine (l Phe) fibrils with crown ethers (CEs). For this purpose, two different CEs (15 Crown-5 (15C5) and 18-Crown-6 (18C6)) were used. Interestingly, we have observed that both CEs have the ability to arrest fibril formation. However, 18C6 was found to be a better candidate compared to 15C5. Field emission scanning electron microscopy and fluorescence lifetime imaging microscopy were used to monitor the fibril-arresting kinetics of CEs. The arresting process was further confirmed by fluorescence correlation spectroscopy and nuclear magnetic resonance studies. PMID- 27403655 TI - "Silent" thyrotropin (TSH) expression in acromegaly and clinically non functioning pituitary adenomas. AB - INTRODUCTION: The pituitary adenomas secreting thyrotropin (TSH) are considered the rarest type of hormonally active pituitary tumour. In spite of that, many cases are described in the literature. On the other hand, the observations of the co-expression of TSH with other pituitary hormones (mostly with growth hormone [GH]) and "silent" expression of TSH in clinically non-functioning pituitary adenomas (CNFPA) are rather scarce. MATERIAL AND METHODS: Among 93 examined pituitary adenomas, 22 of them were diagnosed as active acromegaly and 71 as clinically non-functioning pituitary adenomas (CNFPA). All of them were immunostained with antibodies against pituitary hormones, including the anti-TSH antibody. TSH-immunopositive adenomas are immunostained also to detect somatostatin receptor subtypes (SSTR 1-5). RESULTS: TSH immunopositivity was found in 4.2% of CNFPA (3/71 tumours) and in 13.6% (3/22) cases of somatotropinomas manifesting as active acromegaly. All of the examined TSH immunopositive adenomas expressed SSTR subtypes except SSTR4. The symptoms of hyperthyroidism were not observed in any of the acromegalic patients co expressing TSH with GH. CONCLUSIONS: Our data confirm the relative rarity of TSH expression or co-expression of TSH in pituitary tumours. In most cases TSH is co expressed with GH in patients with acromegaly and is not accompanied by hyperthyroidism. The "silent" expression of TSH may occur also, although rarely in CNFPA. The strong expression of SSTR in TSH-immunopositive CNFPA ("silent thyrotropinoma") indicates the possibility of the treatment of these tumours with somatostatin analogues. (Endokrynol Pol 2016; 67 (5): 515-518). PMID- 27403656 TI - Caddisfly Inspired Phosphorylated Poly(ester urea)-Based Degradable Bone Adhesives. AB - Bone and tissue adhesives are essential in surgeries for wound healing, hemostasis, tissue reconstruction, and drug delivery. However, there are very few degradable materials with high adhesion strengths that degrade into bioresorbable byproducts. Caddisfly adhesive silk is interesting due to the presence of phosphoserines, which are thought to afford adhesive properties. In this work, phosphoserine-valine poly(ester urea) copolymers with 2% and 5% phosphoserine content were synthesized to mimic caddisfly adhesive silk. Significantly, the materials are ethanol soluble and water insoluble, making them clinically relevant. Their physical properties were quantified, and the adhesion properties were studied on aluminum and bovine bone substrates before and after cross linking with Ca(2+) ions. The adhesive strength of the phosphorylated copolymer on a bone substrate after cross-linking with Ca(2+) was 439 +/- 203 kPa, comparable to commercially available PMMA bone cement (530 +/- 133 kPa). PMID- 27403657 TI - Nanoparticle Assembly and Gelatin Binding Mediated by Triple Helical Collagen Mimetic Peptide. AB - Peptide-conjugated nanoparticles (NPs) have promising potential for applications in biosensing, diagnosis, and therapeutics because of their appropriate size, unique self-assembly, and specific substrate-binding properties. However, controlled assembly and selective target binding are difficult to achieve with simple peptides on NP surfaces because high surface energy makes NPs prone to self-aggregate and adhere nonspecifically. Here, we report the self-assembly and gelatin binding properties of collagen mimetic peptide (CMP) conjugated gold NPs (CMP-NPs). We show that the orientation of CMPs displayed on the NP surface can control NP assembly either by promoting or hindering triple helical folding between CMPs of neighboring NPs. We also show that CMP-NPs can specifically bind to denatured collagen by forming triple-helical hybrids between denatured collagen strands and CMPs, demonstrating their potential use for detection and selective removal of gelatin from protein mixtures. CMP conjugated NPs offer a simple and effective method for NP assembly and for targeting denatured collagens with high specificity. Therefore, they may lead to new types of functional nanomaterials for detection and study of denatured collagen associated with diseases characterized by high levels of collagen degradation. PMID- 27403658 TI - Visible-Light-Driven Selective Photocatalytic Hydrogenation of Cinnamaldehyde over Au/SiC Catalysts. AB - Highly selective hydrogenation of cinnamaldehyde to cinnamyl alcohol with 2 propanol was achieved using SiC-supported Au nanoparticles as photocatalyst. The hydrogenation reached a turnover frequency as high as 487 h(-1) with 100% selectivity for the production of alcohol under visible light irradiation at 20 degrees C. This high performance is attributed to a synergistic effect of localized surface plasmon resonance of Au NPs and charge transfer across the SiC/Au interface. The charged metal surface facilitates the oxidation of 2 propanol to form acetone, while the electron and steric effects at the interface favor the preferred end-adsorption of alpha,beta-unsaturated aldehydes for their selective conversion to unsaturated alcohols. We show that this Au/SiC photocatalyst is capable of hydrogenating a large variety of alpha,beta unsaturated aldehydes to their corresponding unsaturated alcohols with high conversion and selectivity. PMID- 27403659 TI - Computing Biology. PMID- 27403661 TI - Correction: Competitive Mirror Image Phage Display Derived Peptide Modulates Amyloid Beta Aggregation and Toxicity. AB - [This corrects the article DOI: 10.1371/journal.pone.0147470.]. PMID- 27403660 TI - Characterisation of Cultured Mesothelial Cells Derived from the Murine Adult Omentum. AB - The human omentum has been long regarded as a healing patch, used by surgeons for its ability to immunomodulate, repair and vascularise injured tissues. A major component of the omentum are mesothelial cells, which display some of the characteristics of mesenchymal stem/stromal cells. For instance, lineage tracing studies have shown that mesothelial cells give rise to adipocytes and vascular smooth muscle cells, and human and rat mesothelial cells have been shown to differentiate into osteoblast- and adipocyte-like cells in vitro, indicating that they have considerable plasticity. However, so far, long-term cultures of mesothelial cells have not been successfully established due to early senescence. Here, we demonstrate that mesothelial cells isolated from the mouse omentum could be cultured for more than 30 passages. While epithelial markers were downregulated over passages in the mesothelial cells, their mesenchymal profile remained unchanged. Early passage mesothelial cells displayed clonogenicitiy, expressed several stem cell markers, and up to passage 5 and 13, respectively, could differentiate along the adipogenic and osteogenic lineages, demonstrating stem/progenitor characteristics and differentiation potential. PMID- 27403662 TI - Ovarian down Regulation by GnRF Vaccination Decreases Reproductive Tract Tumour Size in Female White and Greater One-Horned Rhinoceroses. AB - Reproductive tract tumours, specifically leiomyoma, are commonly found in female rhinoceroses. Similar to humans, tumour growth in rhinoceroses is thought to be sex hormone dependent. Tumours can form and expand from the onset of ovarian activity at puberty until the cessation of sex-steroid influences at senescence. Extensive tumour growth results in infertility. The aim of this study was to down regulate reproductive function of tumour-diseased and infertile females to stop further tumour growth using a Gonadotropin releasing factor (GnRF) vaccine. Four infertile southern white (Ceratotherium simum simum) and three Greater one-horned rhinoceroses (rhinoceros unicornis) with active ovaries and 2.7 +/- 0.9 and 14.0 +/- 1.5 reproductive tract tumours respectively were vaccinated against GnRF (Improvac(r), Zoetis, Germany) at 0, 4 and 16 weeks and re-boostered every 6-8 months thereafter. After GnRF vaccination ovarian and luteal activity was suppressed in all treated females. Three months after vaccination the size of the ovaries, the number of follicles and the size of the largest follicle were significantly reduced (P<0.03). Reproductive tract tumours decreased significantly in diameter (Greater-one horned rhino: P<0.0001; white rhino: P<0.01), presumably as a result of reduced sex-steroid influence. The calculated tumour volumes were reduced by 50.8 +/- 10.9% in Greater one-horned and 48.6 +/- 12.9% in white rhinoceroses. In conclusion, GnRF vaccine effectively down regulated reproductive function and decreased the size of reproductive tract tumours in female rhinoceros. Our work is the first to use down regulation of reproductive function as a symptomatic treatment against benign reproductive tumour disease in a wildlife species. Nonetheless, full reversibility and rhinoceros fertility following GnRF vaccination warrants further evaluation. PMID- 27403663 TI - Time Varying Apparent Volume of Distribution and Drug Half-Lives Following Intravenous Bolus Injections. AB - We present a model that generalizes the apparent volume of distribution and half life as functions of time following intravenous bolus injection. This generalized model defines a time varying apparent volume of drug distribution. The half-lives of drug remaining in the body vary in time and become longer as time elapses, eventually converging to the terminal half-life. Two example fit models were substituted into the general model: biexponential models from the least relative concentration error, and gamma variate models using adaptive regularization for least relative error of clearance. Using adult population parameters from 41 studies of the renal glomerular filtration marker 169Yb-DTPA, simulations of extracellular fluid volumes of 5, 10, 15 and 20 litres and plasma clearances of 40 and 100 ml/min were obtained. Of these models, the adaptively obtained gamma variate models had longer times to 95% of terminal volume and longer half-lives. PMID- 27403664 TI - Multifold Enhancement of Third-Harmonic Generation in Dielectric Nanoparticles Driven by Magnetic Fano Resonances. AB - Strong Mie-type magnetic dipole resonances in all-dielectric nanostructures provide novel opportunities for enhancing nonlinear effects at the nanoscale due to the intense electric and magnetic fields trapped within the individual nanoparticles. Here we study third-harmonic generation from quadrumers of silicon nanodisks supporting high-quality collective modes associated with the magnetic Fano resonance. We observe nontrivial wavelength and angular dependencies of the generated harmonic signal featuring a multifold enhancement of the nonlinear response in oligomeric systems. PMID- 27403665 TI - Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate. AB - Gram-negative bacteria such as E. coli use tripartite efflux pumps such as AcrAB TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding. PMID- 27403666 TI - Toward a General Yet Effective Computational Approach for Diffusive Problems: Variable Diffusion Tensor and DVR Solution of the Smoluchowski Equation along a General One-Dimensional Coordinate. AB - A generalization to arbitrary large amplitude motions of a recent approach to the evaluation of diffusion tensors [ J. Comput. Chem. , 2009 , 30 , 2 - 13 ] is presented and implemented in a widely available package for electronic structure computations. A fully black-box tool is obtained, which, starting from the generation of geometric structures along different kinds of paths, proceeds toward the evaluation of an effective diffusion tensor and to the solution of one dimensional Smoluchowski equations by a robust numerical approach rooted in the discrete variable representation (DVR). Application to a number of case studies shows that the results issuing from our approach are identical to those delivered by previous software (in particular DiTe) for rigid scans along a dihedral angle, but can be improved by employing relaxed scans (i.e., constrained geometry optimizations) or even more general large amplitude paths. The theoretical and numerical background is robust and general enough to allow quite straightforward extensions in several directions (e.g., inclusion of reactive paths, solution of Fokker-Planck or stochastic Liouville equations, multidimensional problems, free energy rather than electronic-energy driven processes). PMID- 27403667 TI - Surgical Problems and Adjusting to More Time with the Computer. PMID- 27403669 TI - Updates in Pediatric Surgery. PMID- 27403668 TI - Aluminum in Vaccines: Addressing Parents' Concerns. AB - With myriad frightening stories on the Internet about vaccines, parents are frequently presenting to the pediatrician with questions about the safety of vaccine ingredients, and pediatricians need to be ready to listen to families with a kind ear. Pediatricians must also feel prepared to offer thoughtful, knowledgeable advice, appreciating the parent's concerns and educating them about the irrefutable benefits as well as the potential risks of vaccination. [Pediatr Ann. 2016;45(7):e231-e233.]. PMID- 27403670 TI - Paradigm Shifts in the Treatment of Appendicitis. AB - Acute appendicitis is the most common cause of emergent surgery in children. Historically, surgical dogma dictated emergent appendectomy due to concern for impending perforation. Recently, however, there has been a paradigm shift in both the understanding of its pathophysiology as well as its treatment to more nonoperative management. No longer is it considered a spectrum from uncomplicated appendicitis inevitably progressing to complicated appendicitis over time. Rather, uncomplicated and complicated appendicitis are now considered two distinct pathophysiologic entities. This change requires not only educating the patients and their families but also the general practitioners who will be managing treatment expectations and caring for patients long term. In this article, we review the pathophysiology of appendicitis, including the differentiation between uncomplicated and complicated appendicitis, as well as the new treatment paradigms. [Pediatr Ann. 2016;45(7):e235-e240.]. PMID- 27403671 TI - Management of Abdominal Solid Organ Injury After Blunt Trauma. AB - Injury to the solid abdominal organs-liver, spleen, kidney, and pancreas-is one of the most common injury patterns in pediatric blunt trauma. Pediatric trauma centers are becoming increasingly successful in managing these injuries without operative intervention. Well-validated guidelines have been established for liver and spleen injury management, and operative intervention is reserved for patients who show evidence of active bleeding after resuscitation. No such guidelines yet exist for the management of traumatic injury of the kidney or pancreas. Exploratory laparotomy remains the treatment of choice in patients suffering hemodynamic collapse, but interventional radiologic or endoscopic procedures are increasingly used to manage all but the most devastating solid organ injuries. [Pediatr Ann. 2016;45(7):e241-e246.]. PMID- 27403672 TI - Intestinal Rotation Anomalies. AB - Intestinal rotation abnormality (IRA) predisposes to lethal midgut volvulus. An understanding of intestinal development illustrates the process of normal intestinal rotation and fixation. An appreciation of the clinical presentation and consequences of missed IRA will enhance clinical suspicion and timely evaluation. Selecting the appropriate imaging modality to diagnose IRA requires an understanding of the benefits and limitations of each. The Ladd's procedure continues to be the appropriate surgical treatment for IRA with or without volvulus. Laparoscopy has emerged as an option for the diagnosis and treatment of IRA. Populations in which IRA is always associated, but a Ladd's procedure rarely required, include patients with congenital diaphragmatic hernia and abdominal wall defects. Prevalence of IRA is higher in children with congenital heart disease and heterotaxy syndrome; asymptomatic patients require multidisciplinary consideration of the risks and benefits of screening for IRA, whether a Ladd's procedure is required, and the timing thereof. [Pediatr Ann. 2016;45(7):e247 e250.]. PMID- 27403673 TI - Splenic Cysts. AB - Splenic cysts are rare in the United States but more common in regions of the world where Echinococcus is endemic. Cysts are typically classified as true cysts or pseudocysts. True cysts can be parasitic or nonparasitic in origin, whereas most pseudocysts are a result of previous trauma. Recent recognition of features shared by true cysts and pseudocysts suggests the classification system may need to be revised. The prevalence of splenic cysts has increased secondary to the widespread use of abdominal imaging and successful nonoperative management of traumatic splenic injuries. Treatment previously consisted primarily of total splenectomy. However, recognition of the importance of the spleen throughout a patient's life has led to changes in the management of splenic disease. Advances in the testing and preoperative localization of splenic lesions have also led to increased efforts in splenic conservation. [Pediatr Ann. 2016;45(7):e251-e256.]. PMID- 27403674 TI - Pediatric Chronic Abdominal Pain and Median Arcuate Ligament Syndrome: A Review and Psychosocial Comparison. AB - Chronic abdominal pain (CAP) occurs in children and adolescents with a reported prevalence of 4% to 41% with significant direct and indirect costs to the child, family, and society. Median arcuate ligament syndrome (MALS) is a vascular compression syndrome of the celiac artery that may cause symptoms of epigastric pain and weight loss and is a frequently overlooked cause of CAP in the pediatric population. We have observed that the psychosocial presentation of patients with MALS is notable for various psychiatric comorbidities. In this article, we review MALS as well as our study results of the psychosocial profile of 30 MALS patients. Our data suggest that children and adolescents with MALS have similar psychosocial profiles to children with other gastrointestinal disorders resulting in CAP. The overlap of physical and psychosocial symptoms of patients who have MALS with other CAP disorders leads us to recommend that patients with CAP should be evaluated for MALS. [Pediatr Ann. 2016;45(7):e257-e264.]. PMID- 27403675 TI - A Diagnostic Approach to Autoimmune Disorders: Laboratory Evaluation: Part 2. AB - Pediatricians and other pediatric health care providers in primary care settings are often faced with the challenge of evaluating patients with suspected autoimmune disorders. The first and most important step in evaluating children with suspected autoimmune disorders is taking a detailed history and performing a thorough physical examination. This step helps narrow the diagnosis, and thus helps determine appropriate laboratory evaluations. The results of laboratory tests need to be interpreted within the clinical context. It is also important to recognize that the laboratory tests have different diagnostic values in children as compared to adults. [Pediatr Ann. 2016;45(7):e265-e271.]. PMID- 27403676 TI - The effects of limited adventitiectomy on vascular anastomosis: An experimental study in rats. AB - OBJECTIVE: Blockages in anastomotic vessels cause complete loss of free tissue transfer and replanted limb. Many studies have been conducted in the last 30 years to solve this problem. There are insufficient studies dealing with the effects of the limited adventitiectomy done before surgery for sympathetic overactivity leading situations. The aim of this experimental study is to reveal the effects of limited adventitiectomy. METHODS: In this study, limited adventitiectomy was performed in a wide area before surgery, and the effect of this practice on the vessel diameter and anastomosis was investigated. RESULTS: Rapidly growing dilatation and increase in vessel diameter was observed, and dilatation continued in the limited adventitiectomy group. CONCLUSIONS: The preoperative performed limited adventitiectomy is a useful preparation for super microsurgery. Especially in clinical practice before the free flap surgery, limited adventitiectomy can be applied if the recipient site is expected to have vascular problems. PMID- 27403677 TI - New Glucocyclic RGD Dimers for Positron Emission Tomography Imaging of Tumor Integrin Receptors. AB - Most studies of radiolabeled arginine-glycine-aspartic acid (RGD) peptides have shown in vitro affinity for integrin alphanubeta3, allowing for the targeting of receptor-positive tumors in vivo. However, major differences have been found in the pharmacokinetic profiles of different radiolabeled RGD peptide analogs. The purposes of this study were to prepare (64)Cu-DOTA-gluco-E[c(RGDfK)]2 (R8), (64)Cu-NOTA-gluco-E[c(RGDfK)]2 (R9), and (64)Cu-NODAGA-gluco-E[c(RGDfK)]2 (R10) and compare their pharmacokinetics and tumor imaging properties using small animal positron emission tomography (PET). All three compounds were produced with high specific activity within 10 minutes. The IC50 values were similar for all the substances, and their affinities were greater than that of c(RGDyK). R8, R9, and R10 were stable for 24 hours in human and mouse serums and showed high uptake in U87MG tumors with high tumor-to-blood ratios. Compared to the control, a cyclic RGD peptide dimer without glucosamine, R10, showed low uptake in the liver. Because of their good imaging qualities and improved pharmacokinetics, (64)Cu-labeled dimer RGD conjugates (R8, R9, and R10) may have potential applications as PET radiotracers. R9 (NOTA) with highly in vivo stability consequentially showed an improved PET tumor uptake than R8 (DOTA) or R10 (NODAGA). PMID- 27403678 TI - Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage. AB - RATIONALE: We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain. OBJECTIVES: To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model. METHODS: We identified healthy volunteers that were naturally colonized with pneumococcus and, after clearance of their natural carriage episode, challenged them with a heterologous 6B strain. In another cohort of volunteers we assessed 6BPS-specific, PspA-specific, and PspC specific IgG and IgA plasma and memory B-cell populations before and 7, 14, and 35 days after experimental pneumococcal inoculation. MEASUREMENTS AND MAIN RESULTS: Heterologous challenge with 6B resulted in 50% carriage among volunteers with previous natural pneumococcal carriage. Protection from carriage was associated with a high number of circulating 6BPS IgG-secreting memory B cells at baseline. There were no associations between protection from carriage and baseline levels of 6BPS IgG in serum or nasal wash, PspA-specific, or PspC specific memory B cells or plasma cells. In volunteers who did not develop carriage, the number of circulating 6BPS memory B cells decreased and the number of 6BPS plasma cells increased postinoculation. CONCLUSIONS: Our data indicate that naturally acquired PS-specific memory B cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition. PMID- 27403679 TI - Biological markers for anxiety disorders, OCD and PTSD - a consensus statement. Part I: Neuroimaging and genetics. AB - OBJECTIVES: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). METHODS: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. RESULTS: The present article (Part I) summarises findings on potential biomarkers in neuroimaging studies, including structural brain morphology, functional magnetic resonance imaging and techniques for measuring metabolic changes, including positron emission tomography and others. Furthermore, this review reports on the clinical and molecular genetic findings of family, twin, linkage, association and genome-wide association studies. Part II of the review focuses on neurochemistry, neurophysiology and neurocognition. CONCLUSIONS: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high-quality research has accumulated that will improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD. PMID- 27403681 TI - A Sports Medicine Watcher. PMID- 27403683 TI - Coming in sportsmedicine. PMID- 27403680 TI - Influence of Incidental Discrete Emotions on Health Risk Perception and Persuasion. AB - This research examines the effects of two incidental discrete emotions-fear and anger-on health risk perception (i.e., perceived susceptibility to a health problem) and persuasion. In two experiments, fear and anger were induced before participants were exposed to a public service announcement that advocated sun protection behaviors to prevent skin cancer (Experiment 1) or flossing to prevent gum diseases (Experiment 2). It was found that fearful participants perceived greater susceptibility to the health risk than angry participants and those who were in a neutral affective state. Angry participants did not differ from those in a neutral affective state in terms of perceived susceptibility. There was mixed evidence that fear exerted an indirect effect on attitude toward the recommended health behavior and intention to perform the health behavior through health risk perception. Theoretical and practical implications of the findings are discussed. PMID- 27403685 TI - Scanning sports. PMID- 27403686 TI - Sportsmedicine forum. PMID- 27403687 TI - A Race Is a Race Is a Race. PMID- 27403690 TI - Exercise-Related Sudden Death: Cardiovascular Evaluation of Exercisers (Part 2 of 2). AB - In brief: Part 1 of this two-part series of articles discussed the risks and factors associated with exercise-related sudden death. In this article the author discusses a primary goal of the cardiovascular evaluation of exercisers: to identify cardiovascular conditions that carry a risk of exercise-related sudden death. These conditions include hypertrophic cardiomyopathy, coronary heart disease, congenital anomalies of the coronary arteries, and others. The evaluation process includes obtaining the patient's medical history, conducting a physical examination, and analyzing the laboratory, ECG, and echocardiography tests indicated by the initial evaluation. The athletic heart syndrome and important clinical points of certain cardiovascular conditions must be considered in the evaluation process. PMID- 27403691 TI - Primary Care Sports Medicine: A Full-Timer's Perspective. AB - In brief: This article describes the history and structure of the Sports Medicine Center of Akron, Ohio, which was established in 1983 with a family physician as its medical director. The author discusses the direct and indirect patient care services offered and the types of injuries seen at the center. He also outlines the opportunities and potential for primary care physicians who wish to enter the field of sports medicine on a full-time basis, particularly in the capacity of medical director of a center like the one described. Advantages, disadvantages, and pitfalls of such a career change are presented, along with steps to take in preparation for pursuing such an endeavor. PMID- 27403692 TI - Resistance Training: Exercise Prescription (Part 4 of 4). AB - In brief: The first part of this series of articles discussed basic concepts of resistance training; parts 2 and 3 continued with a discussion of physiological responses and adaptations that occur as a result of such training. In this fourth and concluding article, the authors discuss resistance training as exercise prescription and outline the program design process. They point out the importance of making preliminary assessments; defining specific goals and expectations; and evaluating the individual needs, goals, and demands of the participants to help them benefit from the program as much as possible. PMID- 27403693 TI - Brain Contusion and Cervical Fracture in a Professional Boxer. AB - In brief: A 22-year-old professional boxer suffered a brain contusion associated with uncal herniation and cervical spine fracture in the ring. Unlike most catastrophic acute brain injuries in boxing, this one had a relatively favorable outcome. The authors discuss the role of emergency medical services in minimizing brain injury in boxing and the treatment of acute head trauma. PMID- 27403694 TI - Unexplained Shoulder Pain in a Weight Lifter. AB - In brief: This case report describes how the authors diagnosed the shoulder pain of a weight lifter through the use of radionuclide imaging. This technique is especially valuable because it detects increased vascularity or increased metabolic activity of lesions long before such changes can be seen on plain radiographs or other imaging modalities. PMID- 27403695 TI - Training Habits and Injury Experience in Distance Runners: Age-and Sex-Related Factors. AB - In brief: An 80-item questionnaire was used to study the variations by age and sex in the training habits and injury experience of 688 adult entrants in a 10 mile road race in southern Ontario. The results showed that runners over the age of 30 years tend to train at a slower pace than younger runners. On the average, men trained over somewhat longer distances and at a faster pace than women of the same age, but women ran more times per week. Older athletes tended toward a higher weekly mileage and entered the longer distance races. While 57% of all respondents reported at least one injury during the 12 months preceding our study, there was no significant variation by age or sex. PMID- 27403696 TI - Does Cardiac Rehabilitation After Myocardial Infarction Favorably. AB - In brief: This review article discusses the limitations of 14 randomized controlled trials of exercise rehabilitation for patients who had sustained a myocardial infarction. Seven of nine major trials involved 3,222 patients, whose conditions were followed for one to nine years; total mortality was reduced by 20% to 50% in these studies. Although pooling this information to obtain statistical significance is difficult, the results are compatible with a substantial therapeutic benefit. In addition to the positive effects on total mortality, exercise can improve mood state and increase physical working capacity. Thus, there is solid ground for prescribing exercise-centered cardiac rehabilitation after an uncomplicated myocardial infarction. PMID- 27403697 TI - Case Studies in Sports Nutrition. AB - In brief: With the recent plethora of research indicating that food affects performance, athletes are eager to learn how to eat to win. They recognize that sound nutrition practices are an integral part of their training program. Hence, sports-active people of all ages and athletic abilities are increasingly receptive to professional nutrition advice. This article presents two case reports of athletes who consulted the author for advice regarding diverse problems: One wanted to stabilize her blood sugar and lose weight; the other wished to gain weight. Both wanted to enhance their athletic performance. PMID- 27403698 TI - Spine Trauma Associated With Off-Road Vehicles. AB - In brief: A seven-year review of 1,447 cases of spine trauma showed a 10% increase in sports-related spine trauma from 1980 to 1986; 53 cases were associated with use of off-road vehicles (ATVs, snowmobiles, and motorized dirt bikes). Of these 53 injuries, the major contributing factors were alcohol or drug use, inadequate lighting, poor judgment, and young age. The authors suggest the development of safe riding areas, legislation governing safe operation of these vehicles, and a major public education campaign specifically geared toward parents, warning them of the dangers of allowing children to operate these machines. PMID- 27403699 TI - Does Electricity Speed Healing of Nonunion Fractures? AB - Traditionally, surgeons have performed bone-graft surgery on athletes (and others) with traumatic nonunion fractures; nowadays, they may be likely to prescribe electric bone-growth stimulators. But physicians have yet to agree on the usefulness of those devices. PMID- 27403700 TI - Beyond the Pedometer: New Tools for Monitoring Activity. AB - Devices and methods for measuring physical activity are becoming more accurate and economical, and researchers are using them to study topics ranging from the aerobic capacity of children to the job performance of military aircrews. PMID- 27403701 TI - Sports Medicine: Where Do We Go From Here? PMID- 27403702 TI - Getting Fit for Life: Can Exercise Reduce Stress? AB - Many people exercise to feel better psychologically as well as physically. Staying fit does seem to help reduce stress, but researchers don't yet know how or even how well-it works. PMID- 27403704 TI - Strength arid Endurance of the Neck Muscles. PMID- 27403703 TI - Pedaling Through Umbria: Bicycle Chic. AB - A cyclist offers this day-by-day account of riding through the hills of central Italy. PMID- 27403706 TI - Ipilimumab in melanoma. AB - INTRODUCTION: The treatment of melanoma is evolving rapidly over the past few years. Patients with BRAFv600 mutations can be treated with a combination of a BRAF-inhibitor and an MEK-inhibitor. Patients with BRAF wild-type tumors and BRAFv600 mutated tumors can be treated with immunotherapy i.e. check point inhibitors. AREAS COVERED: We conducted a comprehensive review of the literature on the efficacy and predictive markers, safety, and pharmacoeconomics of ipilimumab in melanoma Expert commentary: Ipilimumab was the first check point inhibitor reaching the clinic, gaining FDA and EMA approval for metastatic melanoma in 2011. Ipilimumab was also approved by FDA in the adjuvant setting for patients with high risk, stage III melanoma. The anti-PD1 directed antibodies pembrolizumab and nivolumab are superior to single agent ipilimumab, which is no longer considered the standard first line treatment in metastatic melanoma. The addition ipilimumab to nivolumab is associated with a higher response rate and a better PFS, particularly in patients with PD-L1 negative tumors, albeit at the cost of a steep increase in grade 3-4 adverse event rate. Definitive survival data on this combination are pending and the selection of patients potentially requiring the combination and its pharmacoeconomic implications are to be elucidated. PMID- 27403707 TI - Self-Assembled Tetrahedral DNA Nanostructures Promote Adipose-Derived Stem Cell Migration via lncRNA XLOC 010623 and RHOA/ROCK2 Signal Pathway. AB - Self-assembled tetrahedral DNA nanostructures (TDNs) with precise sizes have been extensively applied in various fields owing to their exceptional mechanical rigidity, structural stability, and modification versatility. In addition, TDNs can be internalized by mammalian cells and remain mainly intact within the cytoplasm by escaping degradation by nucleases. Here, we studied the effects of TDNs on cell migration and the underlying molecular mechanisms. TDNs remarkably enhanced the migration of rat adipose-derived stem cells and down-regulated the long noncoding RNA (lncRNA) XLOC 010623 to activate the mRNA expression of Tiam1 and Rac1. Furthermore, TDNs highly up-regulated the mRNA and protein expression of RHOA, ROCK2, and VCL. These results indicate that TDNs suppressed the transcription of lncRNA XLOC 010623 and activated the TIAM1/RAC1 and RHOA/ROCK2 signaling pathways to promote cell migration. On the basis of these findings, TDNs show a high potential for application in tissue repair and regenerative medicine as a functional three-dimensional DNA nanomaterial. PMID- 27403708 TI - Tobacco policies and on-premise smoking in bars and clubs that cater to young African Americans following the Maryland Clean Indoor Air Act of 2007. AB - African American young adults ages 18-25 smoke less than their Caucasian peers, yet the burden of tobacco-related illness is significantly higher in African Americans than in Caucasians across the lifespan. Little is known about how clean indoor air laws affect tobacco smoking among African American young adults. We conducted a systematic observation of bars and clubs with events targeted to African American adults 18-25 in Baltimore City at two timepoints (October and November of 2008 and 2010) after enforcement of the Maryland Clean Indoor Air Act (CIAA). Twenty venues-selected on the basis of youth reports of popular venues were rated during peak hours. All surveillance checklist items were restricted to what was observable in the public domain. There was a significant decrease in observed indoor smoking after CIAA enforcement. Observed outdoor smoking also decreased, but this change was not significant. Facilities for smoking outdoors increased significantly. The statewide smoking ban became effective February 1, 2008, yet measurable changes in smoking behavior in bars were not evident until the City engaged in stringent enforcement of the ban several months later. PMID- 27403712 TI - Firefighter exercise protocols conducted in an environmental chamber: developing a laboratory-based simulated firefighting protocol. AB - A standard exercise protocol that allows comparisons across various ergonomic studies would be of great value for researchers investigating the physical and physiological strains of firefighting and possible interventions for reducing the demands. We compared the pattern of cardiorespiratory changes from 21 firefighters during simulated firefighting activities using a newly developed firefighting activity station (FAS) and treadmill walking both performed within an identical laboratory setting. Data on cardiorespiratory parameters and core temperature were collected continuously using a portable metabolic unit and a wireless ingestible temperature probe. Repeated measures ANOVA indicated distinct patterns of change in cardiorespiratory parameters and heart rate between conditions. The pattern consisted of alternating periods of peaks and nadirs in the FAS that were qualitatively and quantitatively similar to live fire activities, whereas the same parameters increased logarithmically in the treadmill condition. Core temperature increased in a similarly for both conditions, although more rapidly in the FAS. Practitioner Summary: The firefighting activity station (FAS) yields a pattern of cardiorespiratory responses qualitatively and quantitatively similar to live fire activities, significantly different than treadmill walking. The FAS can be performed in a laboratory/clinic, providing a potentially standardised protocol for testing interventions to improve health and safety and conducting return to duty decisions. PMID- 27403713 TI - Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling. AB - Matrix metalloproteinase-20 (MMP20) is expressed by ameloblasts in developing teeth and MMP20 mutations cause enamel malformation. We established a stably transfected Tet-Off Mmp20-inducible ameloblast-lineage cell line and found that MMP20 expression promoted cell invasion. Previously, we engineered transgenic mice (Tg) that drive Mmp20 expression and showed that Mmp20(+/+)Tg mice had soft enamel. Here we asked if Mmp20 overexpression disrupts ameloblast function. Incisors from Mmp20(+/+) mice expressing the Mmp20 Tg had a striking cell infiltrate which nearly replaced the entire enamel layer. A thin layer of enamel like material remained over the dentin and at the outer tooth surface, but between these regions were invading fibroblasts and epithelial cells that surrounded ectopic bone-like calcifications. Mmp20(+/+)Tg mice had decreased enamel organ cadherin levels compared to the Mmp20 ablated and WT mice and, instead of predominantly locating adjacent to the ameloblast cell membrane, beta catenin was predominantly present within the nuclei of invading cells. Our data suggest that increased cadherin cleavage by transgenic MMP20 in the WT background releases excess beta-catenin, which translocates to ameloblast nuclei to promote cell migration/invasion. Therefore, we conclude that MMP20 plays a role in normal ameloblast migration through tightly controlled Wnt signaling and that MMP20 overexpression disrupts this process. PMID- 27403714 TI - Vegetation change impacts on soil organic carbon chemical composition in subtropical forests. AB - Changes in the chemical composition of soil organic carbon (SOC) might strongly affect the global carbon cycle as it controls the SOC decomposition rate. Vegetation change associated with long-term land use changes is known to strongly impact the chemical composition of SOC; however, data on the impacts of vegetation change following disturbance events of short durations and succession that occur frequently in forest ecosystems via diverse management objectives on SOC chemical composition are negligible. Here we examined the impacts of vegetation changes on the chemical composition of SOC by sampling soils of native broad-leaved forests, planted mixed broad-leaved and coniferous forests, and tea gardens in eastern China. We used nuclear magnetic resonance spectroscopy to quantify SOC chemical composition. We found that among all components of SOC chemical composition, alkyl carbon (C) and aryl C were more liable to change with vegetation than other SOC components. Soil pH was negatively correlated to the relative abundances of alkyl C and N-alkyl C, and Shannon's index of overstory plant species was positively correlated to the relative abundances of phenolic C and aromaticity. Our results suggest that vegetation changes following short disturbance events and succession may strongly alter SOC chemical composition in forest ecosystems. PMID- 27403715 TI - Underwater microscopy for in situ studies of benthic ecosystems. AB - Microscopic-scale processes significantly influence benthic marine ecosystems such as coral reefs and kelp forests. Due to the ocean's complex and dynamic nature, it is most informative to study these processes in the natural environment yet it is inherently difficult. Here we present a system capable of non-invasively imaging seafloor environments and organisms in situ at nearly micrometre resolution. We overcome the challenges of underwater microscopy through the use of a long working distance microscopic objective, an electrically tunable lens and focused reflectance illumination. The diver-deployed instrument permits studies of both spatial and temporal processes such as the algal colonization and overgrowth of bleaching corals, as well as coral polyp behaviour and interspecific competition. By enabling in situ observations at previously unattainable scales, this instrument can provide important new insights into micro-scale processes in benthic ecosystems that shape observed patterns at much larger scales. PMID- 27403716 TI - Enhanced magneto-optical effects in composite coaxial nanowires embedded with Ag nanoparticles. AB - Nanostructures decorated with noble metal nanoparticles (NPs) exhibit potential for use in highly sensitive optoelectronic devices through the localized surface plasmon resonance (LSPR) effect. In this study, Faraday rotation was significantly enhanced through the structural optimization of ferromagnetic (FM)/semiconductor composite nanostructures. Experimental and theoretical results revealed that the position of noble metal NPs significantly influenced the coupling of the LSPR-enhanced electromagnetic field with FM materials. Furthermore, nanostructures embedded with noble metals demonstrated an improved capability to efficiently use the electromagnetic field compared to other structures. The Faraday rotation of ZnO/Ag(NPs)/Fe was enhanced 58 fold compared to that of the ZnO(film)/Fe. This work provides a basis for the design of nanoarchitectures for miniaturized high-performance magneto-optical devices. PMID- 27403717 TI - Biochemical and proteomic characterization of retrovirus Gag based microparticles carrying melanoma antigens. AB - Extracellular vesicles are membraneous particles released by a variety of cells into the extracellular microenvironment. Retroviruses utilize the cellular vesiculation pathway for virus budding/assembly and the retrovirus Gag protein induces the spontaneous formation of microvesicles or virus-like particles (VLPs) when expressed in the mammalian cells. In this study, five different melanoma antigens, MAGEA4, MAGEA10, MART1, TRP1 and MCAM, were incorporated into the VLPs and their localization within the particles was determined. Our data show that the MAGEA4 and MAGEA10 proteins as well as MCAM are expressed on the surface of VLPs. The compartmentalization of exogenously expressed cancer antigens within the VLPs did not depend on the localization of the protein within the cell. Comparison of the protein content of VLPs by LC-MS/MS-based label-free quantitative proteomics showed that VLPs carrying different cancer antigens are very similar to each other, but differ to some extent from VLPs without recombinant antigen. We suggest that retrovirus Gag based virus-like particles carrying recombinant antigens have a potential to be used in cancer immunotherapy. PMID- 27403718 TI - Influence of donor-recipient sex mismatch on long-term survival of pancreatic grafts. AB - To assess the role of sex mismatch on graft survival after pancreas transplantation. We evaluated 24,195 pancreas-transplant recipients reported in the Scientific Registry of Transplant Recipients over a 25-year period. Pancreatic graft survival (PGS) was analyzed according to donor-recipient sex pairing using Kaplan-Meier estimations. Hazard ratios were estimated using Cox proportional hazard models. A total of 14,187 male and 10,008 female recipients were included in final analyses. Mean follow-up was 8.3 +/- 5.7 years. In multivariate analyses, neither recipient sex nor donor sex was associated with pancreatic graft failure (PGF), but donor-recipient sex mismatch (regardless of recipient sex) was an independent predictor of PGS (HR, 1.09; 95% CI, 1.04-1.14; p < 0.001). Compared with M -> M sex-matched recipients in univariate analyses, M -> F and F -> M sex mismatches were associated with an increased risk of PGF. Adjustment for significant recipient and donor factors eliminated the association between F -> M sex mismatch and PGF (HR, 1.02; 95% CI, 0.93-1.10; p = 0.752), but not M -> F (1.09; 1.02-1.17; 0.020). Stratified analyses suggested that the negative effect of donor-recipient sex mismatch could be neutralized in older patients. These findings suggest that donor-recipient sex pairing should be taken into consideration in organ-allocation strategies. PMID- 27403719 TI - A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant. AB - Insertions in the Salmonella enterica fra locus, which encodes the fructose asparagine (F-Asn) utilization pathway, are highly attenuated in mouse models of inflammation (>1000-fold competitive index). Here, we report that F-Asn is bacteriostatic to a fraB mutant (IC50 19 MUM), but not to the wild-type or a fra island deletion mutant. We hypothesized that the presence of FraD kinase and absence of FraB deglycase causes build-up of a toxic metabolite: 6 phosphofructose-aspartate (6-P-F-Asp). We used biochemical assays to assess FraB and FraD activities, and mass spectrometry to confirm that the fraB mutant accumulates 6-P-F-Asp. These results, together with our finding that mutants lacking fraD or the fra island are not attenuated in mice, suggest that the extreme attenuation of a fraB mutant stems from 6-P-F-Asp toxicity. Salmonella FraB is therefore an excellent drug target, a prospect strengthened by the absence of the fra locus in most of the gut microbiota. PMID- 27403720 TI - Single-Crystal X-ray Structures of conductive pi-Stacking Dimers of Tetrakis(alkylthio)benzene Radical Cations. AB - Salts containing radical cations of 1,2,4,5-tetrakis(isopropylthio)benzene (TPB) and 1,2,4,5-tetrakis(ethylthio) benzene (TEB) have been successfully synthesized with . These newly synthesized salts have been characterized by UV-Vis absorption, EPR spectroscopy, conductivity measurement, single crystal X-ray diffraction analysis as well as DFT calculation. This study raises the first crystal structure of conductive pi-stacking radical cation with single phenyl ring and reveals their conductivity has relationship with the stack structure which affected by the substituent. PMID- 27403721 TI - Selectable Ultrasensitive Detection of Hg(2+) with Rhodamine 6G-Modified Nanoporous Gold Optical Sensor. AB - An extremely sensitive fluorescence sensor has been developed for selectively detection of mercury ions based on metallophilic Hg(2+)-Au(+) interactions, which results in an effective release of pre-adsorbed rhodamine 6G (R6G) molecules from the nanoporous gold substrate, associated with a significant decrease of fluorescence intensity. The optical sensor has a detection sensitivity down to 0.6 pM for Hg(2+) and CH3Hg(+) ions, in particular a superior selectivity in a complex aqueous system containing 13 different types of metal ions, meanwhile maintaining a long-term stability after 10 cycles. Such a fluorescence sensor combining multiple advantages therefore present promising potentials in various applications. PMID- 27403722 TI - Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches. AB - The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18beta-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18beta glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA binding function of EBOV NP sheds new light on antiviral drug development. PMID- 27403723 TI - Measurement of Calcium Fluctuations Within the Sarcoplasmic Reticulum of Cultured Smooth Muscle Cells Using FRET-based Confocal Imaging. AB - Maintenance of steady-state calcium (Ca(2+)) levels in the sarcoplasmic reticulum (SR) of vascular smooth muscle cells (VSMCs) is vital to their overall health. A significant portion of intracellular Ca(2+) content is found within the SR stores in VSMCs. As the only intracellular organelle with a close association to the surrounding extracellular space through plasma membrane-SR junctions, the SR can be considered to constitute the first line of response to any irregularity in Ca(2+) transients, or stress experienced by the cell. Among its many functions, one of the most important is its role in the transmission of Ca(2+)-regulated signals throughout the cell to induce further cell-wide reactions downstream. The more common use of cytoplasmic Ca(2+) indicators in this regard is overall insufficient for research into the highly dynamic changes to the intraluminal SR Ca(2+) store that have yet to be fully characterized. Here, we provide a detailed protocol for the direct and clear measurement of luminal SR Ca(2+). This tool is useful for investigation into the nuanced changes in SR Ca(2+) that have significant subsequent effects on the normal function and health of the cell. Fluctuations in SR Ca(2+) content specifically can provide us with a significant amount of information pertaining to cellular responses to disease or stress conditions experienced by the cell. In this method, a modified version of a SR targeted Ca(2+) indicator, D1SR, is used to detect Ca(2+) fluctuations in response to the introduction of agents to cultured rat aortic smooth muscle cells (SMCs). Following incubation with the D1SR indicator, confocal fluorescence microscopy and fluorescence resonance energy transfer (FRET)-based imaging are used to directly observe changes to intraluminal SR Ca(2+) levels under control conditions and with the addition of agonist agents that function to induce intracellular Ca(2+) movement. PMID- 27403724 TI - Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia. AB - Antibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG). Reconstructed single-domain antibodies were reactive to both HCV antigens and potentially liver-derived human proteins. Moreover, over the course of antiviral therapy, a substantial "de-evolution" of a distinct sub repertoire was discovered, to which proteomically identified cryoprecipitation prone autoantibodies belonged. This sub-repertoire was characterized by IGHJ6*03 derived, long, hydrophobic complementarity determining region (CDR-H3). This study provides a proof-of-concept of de novo mining of autoantibodies and corresponding autoantigen candidates in a disease-specific context in human, thus facilitating future reverse-translational research for the discovery of novel biomarkers and the development of antigen-specific immunotherapy against various autoantibody-related disorders. PMID- 27403725 TI - Reproduction of the long-spined sea urchin Diadema setosum in the Gulf of Aqaba - implications for the use of gonad-indexes. AB - As global warming and climate-change proceeds ever more rapidly, organisms depending on seasonal cues to synchronize reproduction face an unclear future. Reproduction in Diadema setosum in the Gulf of Aqaba (Red Sea) is seasonal, with mature individuals occurring from July to October. Gonad indexes (GI), in contrast, indicate that spawning occurs from August through December and suggests two main spawning events. Histological analysis, however, indicate that the second peak of GI values cannot be related to spawning, but rather correspond to recovering individuals. In Diadema, examination of GI values alone may thus lead to erroneous conclusions. GI was moderately-strong positively correlated with sea surface temperatures, but not with chlorophyll-a concentrations or photoperiod. Spawning coincides with the onset of the annual chlorophyll-a increase, however, which might be advantageous for nutrition of the developing larvae. First significant GI increase coincides with the shortening of day-length, which may act as a cue for D. setosum gametogenesis. Gametogenesis is highly synchronised between sexes, although the mature phase of females exceeds that of males. The non-complete overlap may represent sampling bias or represent an adaptive strategy for enhancing fertilisation success. Skewed sex ratios (?:? 1:0.59, n = 360) in the Gulf of Aqaba may be related to pollution. PMID- 27403726 TI - Detecting Cortex Fragments During Bacterial Spore Germination. AB - The process of endospore germination in Clostridium difficile, and other Clostridia, increasingly is being found to differ from the model spore-forming bacterium, Bacillus subtilis. Germination is triggered by small molecule germinants and occurs without the need for macromolecular synthesis. Though differences exist between the mechanisms of spore germination in species of Bacillus and Clostridium, a common requirement is the hydrolysis of the peptidoglycan-like cortex which allows the spore core to swell and rehydrate. After rehydration, metabolism can begin and this, eventually, leads to outgrowth of a vegetative cell. The detection of hydrolyzed cortex fragments during spore germination can be difficult and the modifications to the previously described assays can be confusing or difficult to reproduce. Thus, based on our recent report using this assay, we detail a step-by-step protocol for the colorimetric detection of cortex fragments during bacterial spore germination. PMID- 27403727 TI - A Simple Approach to Manipulate Dissolved Oxygen for Animal Behavior Observations. AB - The ability to manipulate dissolved oxygen (DO) in a laboratory setting has significant application to investigate a number of ecological and organismal behavior questions. The protocol described here provides a simple, reproducible, and controlled method to manipulate DO to study behavioral response in aquatic organisms resulting from hypoxic and anoxic conditions. While performing degasification of water with nitrogen is commonly used in laboratory settings, no explicit method for ecological (aquatic) application exists in the literature, and this protocol is the first to describe a protocol to degasify water to observe organismal response. This technique and protocol were developed for direct application for aquatic macroinvertebrates; however, small fish, amphibians, and other aquatic vertebrates could be easily substituted. It allows for easy manipulation of DO levels ranging from 2 mg/L to 11 mg/L with stability for up to a 5 min animal-observation period. Beyond a 5 min observation period water temperatures began to rise, and at 10 min DO levels became too unstable to maintain. The protocol is scalable to the study organism, reproducible, and reliable, allowing for rapid implementation into introductory teaching labs and high-level research applications. The expected results of this technique should relate dissolved oxygen changes to behavioral responses of organisms. PMID- 27403728 TI - Stripe Assay to Study the Attractive or Repulsive Activity of a Protein Substrate Using Dissociated Hippocampal Neurons. AB - Growing axons develop a highly motile structure at their tip, termed the growth cone. The growth cone contacts extracellular environmental cues to navigate axonal growth. Netrin, slit, semaphorin, and ephrins are known guidance molecules that can attract or repel axons upon binding to receptors and co-receptors on the axon. The activated receptors initiate various signaling molecules in the growth cone that alter the structure and movement of the neuron. Here, we describe the detailed protocol for a stripe assay to assess the ability of a guidance molecule to attract or repel neurons. In this method, dissociated hippocampal neurons from E15.5 mice are cultured on laminin-coated dishes processed with alternating stripes of ectodomain of fibronectin and leucine-rich transmembrane protein-2 (FLRT2) and control immunoglobulin G (IgG) fragment crystallizable region (Fc) protein. Both axons and cell bodies were strongly repelled from the FLRT2-coated stripe regions after 24 h of culture. Immunostaining with tau1 showed that ~90% of the neurons were distributed on the Fc-coated stripes compared to the FLRT2-Fc coated stripes (~10%). This result indicates that FLRT2 has a strong repulsive effect on these neurons. This powerful method is applicable not only for primary cultured neurons but also for a variety of other cells, such as neuroblasts. PMID- 27403729 TI - Unbiased Deep Sequencing of RNA Viruses from Clinical Samples. AB - Here we outline a next-generation RNA sequencing protocol that enables de novo assemblies and intra-host variant calls of viral genomes collected from clinical and biological sources. The method is unbiased and universal; it uses random primers for cDNA synthesis and requires no prior knowledge of the viral sequence content. Before library construction, selective RNase H-based digestion is used to deplete unwanted RNA - including poly(rA) carrier and ribosomal RNA - from the viral RNA sample. Selective depletion improves both the data quality and the number of unique reads in viral RNA sequencing libraries. Moreover, a transposase based 'tagmentation' step is used in the protocol as it reduces overall library construction time. The protocol has enabled rapid deep sequencing of over 600 Lassa and Ebola virus samples-including collections from both blood and tissue isolates-and is broadly applicable to other microbial genomics studies. PMID- 27403730 TI - Hybrid Integration of Graphene Analog and Silicon Complementary Metal-Oxide Semiconductor Digital Circuits. AB - We demonstrate a hybrid integration of a graphene-based analog circuit and a silicon-based digital circuit in order to exploit the strengths of both graphene and silicon devices. This mixed signal circuit integration was achieved using a three-dimensional (3-D) integration technique where a graphene FET multimode phase shifter is fabricated on top of a silicon complementary metal-oxide semiconductor field-effect transistor (CMOS FET) ring oscillator. The process integration scheme presented here is compatible with the conventional silicon CMOS process, and thus the graphene circuit can successfully be integrated on current semiconductor technology platforms for various applications. This 3-D integration technique allows us to take advantage of graphene's excellent inherent properties and the maturity of current silicon CMOS technology for future electronics. PMID- 27403731 TI - Prediction Models of Retention Indices for Increased Confidence in Structural Elucidation during Complex Matrix Analysis: Application to Gas Chromatography Coupled with High-Resolution Mass Spectrometry. AB - Monitoring of volatile and semivolatile compounds was performed using gas chromatography (GC) coupled to high-resolution electron ionization mass spectrometry, using both headspace and liquid injection modes. A total of 560 reference compounds, including 8 odd n-alkanes, were analyzed and experimental linear retention indices (LRI) were determined. These reference compounds were randomly split into training (n = 401) and test (n = 151) sets. LRI for all 552 reference compounds were also calculated based upon computational Quantitative Structure-Property Relationship (QSPR) models, using two independent approaches RapidMiner (coupled to Dragon) and ACD/ChromGenius software. Correlation coefficients for experimental versus predicted LRI values calculated for both training and test set compounds were calculated at 0.966 and 0.949 for RapidMiner and at 0.977 and 0.976 for ACD/ChromGenius, respectively. In addition, the cross validation correlation was calculated at 0.96 from RapidMiner and the residual standard error value obtained from ACD/ChromGenius was 53.635. These models were then used to predict LRI values for several thousand compounds reported present in tobacco and tobacco-related fractions, plus a range of specific flavor compounds. It was demonstrated that using the mean of the LRI values predicted by RapidMiner and ACD/ChromGenius, in combination with accurate mass data, could enhance the confidence level for compound identification from the analysis of complex matrixes, particularly when the two predicted LRI values for a compound were in close agreement. Application of this LRI modeling approach to matrixes with unknown composition has already enabled the confirmation of 23 postulated compounds, demonstrating its ability to facilitate compound identification in an analytical workflow. The goal is to reduce the list of putative candidates to a reasonable relevant number that can be obtained and measured for confirmation. PMID- 27403732 TI - Phenolic Compounds from Cyclopia intermedia (Honeybush Tea). 1. AB - The processed leaves and stems of Cyclopia intermedia contain 4-hydroxycinnamic acid, the isoflavones formononetin, afrormosin, calycosin, pseudobaptigen, and fujikinetin, the flavanones naringenin, eriodictyol, hesperitin, and hesperidin, the coumestans medicagol, flemichapparin, and sophoracoumestan B, the xanthones mangiferin and isomangiferin, the flavone luteolin, and the inositol (+)-pinitol. PMID- 27403733 TI - Dendrimer-Capped Gold Nanoparticles for Highly Reliable and Robust Surface Enhanced Raman Scattering. AB - Dendrimer-stabilized gold nanoparticles (Au-Den) were prepared by a facile solution based method for a highly reliable and robust surface enhanced Raman scattering (SERS) substrate. Au-Den was selectively attached on the surface of reduced graphene oxide (rGO) by noncovalent interactions between the Au capping dendrimer and the graphene surface. Au-Den/rGO exhibits the outstandingly stable and highly magnified Raman signal with an enhancement factor (EF) of 3.9 * 10(7) that enables detection of R6G dyes with concentration as low as 10 nM, retaining 95% of the Raman signal intensity after 1 year. The remarkable stability and enhancement originated not only from a simple combination of the electromagnetic and chemical mechanism of SERS but also from intensified packing density of stable Au-Den on the graphene substrate due to the firm binding between the dendrimer capped metal nanoparticles and the graphene substrate. This method is not limited to the gold nanoparticles and G4 dendrimer used herein, but also can be applied to other dendrimers and metal nanoparticles, which makes the material platform suggested here superior to other SERS substrates. PMID- 27403734 TI - Correction to Use of Bromine and Bromo-Organic Compounds in Organic Synthesis. PMID- 27403735 TI - A central role for phosphatidic acid as a lipid mediator of regulated exocytosis in apicomplexa. AB - Lipids are commonly known for the structural roles they play, however, the specific contribution of different lipid classes to wide-ranging signalling pathways is progressively being unravelled. Signalling lipids and their associated effector proteins are emerging as significant contributors to a vast array of effector functions within cells, including essential processes such as membrane fusion and vesicle exocytosis. Many phospholipids have signalling capacity, however, this review will focus on phosphatidic acid (PA) and the enzymes implicated in its production from diacylglycerol (DAG) and phosphatidylcholine (PC): DGK and PLD respectively. PA is a negatively charged, cone-shaped lipid identified as a key mediator in specific membrane fusion and vesicle exocytosis events in a variety of mammalian cells, and has recently been implicated in specialised secretory organelle exocytosis in apicomplexan parasites. This review summarises the recent work implicating a role for PA regulation in exocytosis in various cell types. We will discuss how these signalling events are linked to pathogenesis in the phylum Apicomplexa. PMID- 27403736 TI - Red Mud and Li-Ion Batteries: A Magnetic Connection. AB - Exceptional Li-ion battery performance is presented with the oxide component of the anode was extracted from red mud by simple magnetic separation and applied directly without any further processing. The extracted material has gamma-Fe2 O3 as the major phase with inter-dispersed phases of Ti, Al, and Si oxides. In a half-cell assembly, the phase displayed a reversible capacity (~697 mA h g(-1) ) with excellent stability upon cycling. Interestingly, the stability is rendered by the multiphase constitution of the material with the presence of other electrochemically inactive metal oxides, such as Al2 O3 , SiO2 , and Fe2 TiO4 , which could accommodate the strain and facilitate release during the charge discharge processes in the electrochemically active maghemite component. We fabricated the full-cell assembly with eco-friendly cathode LiMn2 O4 by adjusting the mass loading. Prior to full-cell assembly, an electrochemical pre-lithiation was enforced to overcome the irreversible capacity loss obtained from the anode. The full-cell delivered a capacity of ~100 mA h g(-1) (based on cathode loading) with capacity retention of ~61 % after 2000 cycles under ambient conditions. PMID- 27403738 TI - Sequential CCR5-Tropic HIV-1 Reactivation from Distinct Cellular Reservoirs following Perturbation of Elite Control. AB - BACKGROUND: HIV Elite Controllers may reveal insights into virus persistence given they harbour small reservoir sizes, akin to HIV non-controllers treated early with combination antiretroviral therapy. Both groups of patients represent the most promising candidates for interventions aimed at sustained remission or 'cure'. Analytic treatment interruption (ATI) in the latter group leads to stochastic rebound of virus, though it is unclear whether loss of elite control is also associated with similar rebound characteristics. METHODS: We studied three discrete periods of virus rebound during myeloma related immune disruption over 2.5 years in an elite controller who previously underwent autologous stem cell transplantation (ASCT) in the absence of any antiretroviral therapy. Single genome sequencing of the V1-V4 region of env in PBMC and plasma was performed and phylogenies reconstructed. Average pairwise distance (APD) was calculated and non parametric methods used to assess compartmentalisation. Coreceptor usage was predicted based on genotypic algorithms. RESULTS: 122 single genome sequences were obtained (median 26 sequences per rebound). The initial rebounding plasma env sequences following ASCT represented two distinct lineages, and clustered with proviral DNA sequences isolated prior to ASCT. One of the lineages was monophyletic, possibly indicating reactivation from clonally expanded cells. The second rebound occurred 470 days after spontaneous control of the first rebound and was phylogenetically distinct from the first, confirmed by compartmentalisation analysis, with a different cellular origin rather than ongoing replication. By contrast, third rebound viruses clustered with second rebound viruses, with evidence for ongoing evolution that was associated with lymphopenia and myeloma progression. Following ASCT a shift in tropism from CXCR4 tropic viruses to a CCR5-tropic population was observed to persist through to the third rebound. CONCLUSIONS: Our data highlight similarities in the viral reservoir between elite and non-controllers undergoing ATI following allogeneic transplantation. The lack of propagation of CXCR4 using viruses following transplantation warrants further study. PMID- 27403737 TI - Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells. AB - After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/-) retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK) cell-mediated cytotoxicity: i) B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/-) and FcgammaRIIIa deficient (CD16-/-) C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell mediated cytotoxicity; ii) administration of NK1.1 specific IgG2a (mAb PK136) but not irrelevant IgG2a (myeloma M9144) prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii) splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv) purified NK cells from naive C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v) adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi) degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei infected mice kill B cells, suppress humoral immunity and expedite early mortality. PMID- 27403739 TI - Detecting Dysglycemia Using the 2015 United States Preventive Services Task Force Screening Criteria: A Cohort Analysis of Community Health Center Patients. AB - BACKGROUND: In 2015, the United States Preventive Services Task Force (USPSTF) recommended targeted screening for prediabetes and diabetes (dysglycemia) in adults who are aged 40 to 70 y old and overweight or obese. Given increasing prevalence of dysglycemia at younger ages and lower body weight, particularly among racial/ethnic minorities, we sought to determine whether the current screening criteria may fail to identify some high-risk population subgroups. METHODS AND FINDINGS: We investigated the performance of the 2015 USPSTF screening recommendation in detecting dysglycemia among US community health center patients. A retrospective analysis of electronic health record (EHR) data from 50,515 adult primary care patients was conducted. Longitudinal EHR data were collected in six health centers in the Midwest and Southwest. Patients with a first office visit between 2008 and 2010 were identified and followed for up to 3 y through 2013. We excluded patients who had dysglycemia at baseline and those with fewer than two office visits during the follow-up period. The exposure of interest was eligibility for screening according to the 2015 USPSTF criteria. The primary outcome was development of dysglycemia during follow-up, determined by: (1) laboratory results (fasting/2-h postload/random glucose >= 100/140/200 mg/dL [5.55/7.77/11.10 mmol/L] or hemoglobin A1C >= 5.7% [39 mmol/mol]); (2) diagnosis codes for prediabetes or type 2 diabetes; or (3) antidiabetic medication order. At baseline, 18,846 (37.3%) participants were aged >=40 y, 33,537 (66.4%) were overweight or obese, and 39,061 (77.3%) were racial/ethnic minorities (34.6% Black, 33.9% Hispanic/Latino, and 8.7% Other). Overall, 29,946 (59.3%) patients had a glycemic test within 3 y of follow-up, and 8,478 of them developed dysglycemia. Only 12,679 (25.1%) patients were eligible for screening according to the 2015 USPSTF criteria, which demonstrated the following sensitivity and specificity (95% CI): 45.0% (43.9%-46.1%) and 71.9% (71.3%-72.5%), respectively. Racial/ethnic minorities were significantly less likely to be eligible for screening yet had higher odds of developing dysglycemia than whites (odds ratio [95% CI]: Blacks 1.24 [1.09-1.40]; Hispanics 1.46 [1.30-1.64]; and Other 1.33 [1.16-1.54]). In addition, the screening criteria had lower sensitivity in all racial/ethnic minority groups compared to whites. Limitations of this study include the ascertainment of dysglycemia only among patients with available test results and findings that may not be generalizable at the population level. CONCLUSIONS: Targeted diabetes screening based on new USPSTF criteria may detect approximately half of adult community health center patients with undiagnosed dysglycemia and proportionately fewer racial/ethnic minorities than whites. Future research is needed to estimate the performance of these screening criteria in population-based samples. PMID- 27403741 TI - Molecular Cytogenetic Mapping of Satellite DNA Sequences in Aegilops geniculata and Wheat. AB - Fluorescence in situ hybridization (FISH) provides an efficient system for cytogenetic analysis of wild relatives of wheat for individual chromosome identification, elucidation of homoeologous relationships, and for monitoring alien gene transfers into wheat. This study is aimed at developing cytogenetic markers for chromosome identification of wheat and Aegilops geniculata (2n = 4x = 28, UgUgMgMg) using satellite DNAs obtained from flow-sorted chromosome 5Mg. FISH was performed to localize the satellite DNAs on chromosomes of wheat and selected Aegilops species. The FISH signals for satellite DNAs on chromosome 5Mg were generally associated with constitutive heterochromatin regions corresponding to C band-positive chromatin including telomeric, pericentromeric, centromeric, and interstitial regions of all the 14 chromosome pairs of Ae. geniculata. Most satellite DNAs also generated FISH signals on wheat chromosomes and provided diagnostic chromosome arm-specific cytogenetic markers that significantly improved chromosome identification in wheat. The newly identified satellite DNA CL36 produced localized Mg genome chromosome-specific FISH signals in Ae. geniculata and in the M genome of the putative diploid donor species Ae. comosa subsp. subventricosa but not in Ae. comosa subsp. comosa, suggesting that the Mg genome of Ae. geniculata was probably derived from subsp. subventricosa. PMID- 27403742 TI - Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells. AB - We previously examined the effect of brain microvascular endothelial cell (MVEC) transplantation on rat white matter infarction, and found that MVEC transplantation promoted remyelination of demyelinated axons in the infarct region and reduced apoptotic death of oligodendrocyte precursor cells (OPCs). We also found that the conditioned medium (CM) from cultured MVECs inhibited apoptosis of cultured OPCs. In this study, we examined contribution of extracellular vesicles (EVs) contained in the CM to its inhibitory effect on OPC apoptosis. Removal of EVs from the CM by ultracentrifugation reduced its inhibitory effect on OPC apoptosis. To confirm whether EVs derived from MVECs are taken up by cultured OPCs, we labeled EVs with PKH67, a fluorescent dye, and added them to OPC cultures. Many vesicular structures labeled with PKH67 were found within OPCs immediately after their addition. Next we examined the effect of MVEC-derived EVs on OPC behaviors. After 2 days in culture with EVs, there was significantly less pyknotic and more BrdU-positive OPCs when compared to control. We also examined the effect of EVs on motility of OPCs. OPCs migrated longer in the presence of EVs when compared to control. To examine whether these effects on cultured OPCs are shared by EVs from endothelial cells, we prepared EVs from conditioned media of several types of endothelial cells, and tested their effects on cultured OPCs. EVs from all types of endothelial cells we examined reduced apoptosis of OPCs and promoted their motility. Identification of the molecules contained in EVs from endothelial cells may prove helpful for establishment of effective therapies for demyelinating diseases. PMID- 27403744 TI - An Acoustic Analysis of the Genus Microhyla (Anura: Microhylidae) of Sri Lanka. AB - Vocalizing behavior of frogs and toads, once quantified, is useful for systematics, rapid species identification, behavioral experimentation and conservation monitoring. But yet, for many lineages vocalizations remain unknown or poorly quantified, especially in diversity rich tropical regions. Here we provide a quantitative acoustical analysis for all four Sri Lankan congeners of the genus Microhyla. Three of these species are endemic to the island, but Microhyla ornata is regionally widespread. Two of these endemics, M. karunaratnei (Critically Endangered) and M. zeylanica (Endangered), are highly threatened montane isolates; the other, M. mihintalei, is relatively common across the dry lowlands. We recorded and analyzed 100 advertisement calls from five calling males for each species, except for M. zeylanica, which only had 53 calls from three males suitable for analyses. All four species call in choruses and their vocal repertoires are simple compared to most frogs. Their calls contain multiple pulses and no frequency modulation. We quantified eight call characters. Call duration and number of pulses were higher for the two montane isolates (inhabiting cooler habitats at higher altitudes) compared to their lowland congeners. Microhyla zeylanica has the longest call duration (of 1.8 +/- 0.12 s) and the highest number of pulses (of 61-92 pulses). The smallest of the species, Microhyla karunaratnei (16.2-18.3 mm), has the highest mean dominant frequency (3.3 +/- 0.14 kHz) and pulse rate (77 +/- 5.8 pulses per second). The calls separate well in the Principal Component space: PC1 axis is mostly explained by the number of pulses per call and call duration; PC2 is mostly explained by the pulse rate. A canonical means plot of a Discriminant Function analysis shows non overlapping 95% confidence ellipses. This suggests that some call parameters can be used to distinguish these species effectively. We provide detailed descriptions for eight call properties and compare these with congeners for which data is available. This work provides a foundation for comparative bioacoustic analyses and species monitoring while facilitating the systematics of Microhyla across its range. PMID- 27403745 TI - A New Deep-Ultraviolet Transparent Orthophosphate LiCs2PO4 with Large Second Harmonic Generation Response. AB - LiCs2PO4, a new deep-ultraviolet (UV) transparent material, was synthesized by the flux method. The material contains unusual edge-sharing LiO4-PO4 tetrahedra. It exhibits a very short absorption edge of lambda = 174 nm and generates the largest powder second harmonic generation (SHG) response for deep-UV phosphates that do not contain additional anionic groups, i.e., 2.6 times that of KH2PO4 (KDP). First-principles electronic structure analyses confirm the experimental results and suggest that the strong SHG response may originate from the aligned nonbonding O-2p orbitals. The discovery and characterization of LiCs2PO4 provide a new insight into the structure-property relationships of phosphate-based nonlinear optical materials with large SHG responses and short absorption edges. PMID- 27403740 TI - Health Technology Assessment of pathogen reduction technologies applied to plasma for clinical use. AB - Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains.Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed. PMID- 27403743 TI - Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial. AB - : In the present study, we examined the potential symptomatic and/or disease modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 MUg) compared to placebo 11 months after initiation of therapy on United Parkinson's Disease Rating Scale (UPDRS) III scores in the " off " condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the " off " condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01341431. PMID- 27403746 TI - Uranium Metalla-Allenes with Carbene Imido R2 C=U(IV) =NR' Units (R=Ph2 PNSiMe3 ; R'=CPh3 ): Alkali-Metal-Mediated Push-Pull Effects with an Amido Auxiliary. AB - We report uranium(IV)-carbene-imido-amide metalla-allene complexes [U(BIPM(TMS) )(NCPh3 )(NHCPh3 )(M)] (BIPM(TMS) =C(PPh2 NSiMe3 )2 ; M=Li or K) that can be described as R2 C=U=NR' push-pull metalla-allene units, as organometallic counterparts of the well-known push-pull organic allenes. The solid-state structures reveal that the R2 C=U=NR' units adopt highly unusual cis arrangements, which are also reproduced by gas-phase theoretical studies conducted without the alkali metals to remove their potential structure-directing roles. Computational studies confirm the double-bond nature of the U=NR' and U=CR2 interactions, the latter increasingly attenuated by potassium then lithium when compared to the hypothetical alkali-metal-free anion. Combined experimental and theoretical data show that the push-pull effect induced by the alkali metal cations and amide auxiliary gives a fundamental and tunable structural influence over the C=U(IV) =N units. PMID- 27403747 TI - Treatment of complex metacarpal defects with free chimeric iliac osteocutaneous flaps. AB - OBJECTIVE: The aim of this report is to present the clinical results of using free chimeric iliac osteocutaneous flaps based on the periosteal branch of the superficial circumflex iliac artery (SCIA) in complex metacarpal reconstructions. METHODS: Reconstruction using free chimeric iliac osteocutaneous flaps was performed in a series of seven patients who underwent metacarpal reconstruction for complex metacarpal defects between March 2009 and March 2012. The procedure was performed for bone and soft tissue losses associated with posttraumatic infections (four patients) and posttraumatic bone and soft tissue defects (three patients). RESULTS: The skin paddles of the chimeric flaps had a median size of 3 * 7 cm, and the iliac segments had a mean size of 1 * 1 * 3 cm. The median follow up time was 18 months. All the flaps survived completely with no signs of infection. Osseous union occurred within a mean period of 3 months, and the range of motion achieved for the metacarpal phalangeal joints was 0-80 degrees . The patients were satisfied with the aesthetic outcome. CONCLUSIONS: Chimeric iliac osteocutaneous flaps may be a useful alternative for treating complex metacarpal defects because they yield a thinner skin paddle and less bulky bone segment than traditional flaps. PMID- 27403748 TI - Discovery, isolation, and structural characterization of cyclotides from Viola sumatrana Miq. AB - Cyclotides are cyclic peptides from plants in the Violaceae, Rubiaceae, Fabaceae, Cucurbitaceae, and Solanaceae families. They are sparsely distributed in most of these families, but appear to be ubiquitous in the Violaceae, having been found in every plant so far screened from this family. However, not all geographic regions have been examined and here we report the discovery of cyclotides from a Viola species from South-East Asia. Two novel cyclotides (Visu 1 and Visu 2) and two known cyclotides (kalata S and kalata B1) were identified in V. sumatrana. NMR studies revealed that kalata S and kalata B1 had similar secondary structures. Their biological activities were determined in cytotoxicity assays; both had similar cytotoxic activity and were more toxic to U87 cells compared with other cell lines. Overall, the study strongly supports the ubiquity of cyclotides in the Violaceae and adds to our understanding of their distribution and cytotoxic activity. PMID- 27403749 TI - High diversity of Pseudo-nitzschia along the northern coast of Sarawak (Malaysian Borneo), with descriptions of P. bipertita sp. nov. and P. limii sp. nov. (Bacillariophyceae). AB - Forty-eight isolates of Pseudo-nitzschia species were established from the Miri coast of Sarawak (Malaysian Borneo) and underwent TEM observation and molecular characterization. Ten species were found: P. abrensis, P. batesiana, P. fukuyoi, P. kodamae, P. lundholmiae, P. multistriata, P. pungens, P. subfraudulenta, as well as two additional new morphotypes, herein designated as P. bipertita sp. nov. and P. limii sp. nov. This is the first report of P. abrensis, P. batesiana, P. kodamae, P. fukuyoi, and P. lundholmiae in coastal waters of Malaysian Borneo. Pseudo-nitzschia bipertita differs from its congeners by the number of sectors that divide the poroids, densities of band striae, and its cingular band structure. Pseudo-nitzschia limii, a pseudo-cryptic species in the P. pseudodelicatissima complex sensu lato, is distinct by having wider proximal and distal mantles, a higher number of striae, and greater poroid height in the striae of the valvocopula. The species were further supported by the phylogenetic reconstructions of the nuclear-encoded large subunit ribosomal gene and the second internal transcribed spacer. Phylogenetically, P. bipertita clustered with its sister taxa (P. subpacifica + P. heimii); P. limii appears as a sister taxon to P. kodamae and P. hasleana in the ITS2 tree. Pairwise comparison of ITS2 transcripts with its closest relatives revealed the presence of both hemi- and compensatory base changes. Toxicity analysis showed detectable levels of domoic acid in P. abrensis, P. batesiana, P. lundholmiae, and P. subfraudulenta, but both new species tested below the detection limit. PMID- 27403750 TI - Expression of P2 Purinergic Receptors in Mesenchymal Stem Cells and Their Roles in Extracellular Nucleotide Regulation of Cell Functions. AB - Extracellular ATP and other nucleotides induce autocrine and/or paracrine purinergic signalling via activation of the P2 receptors on the cell surface, which represents one of the most common signalling mechanisms. Mesenchymal stem cells (MSC) are a type of multipotent adult stem cells that have many promising applications in regenerative medicine. There is increasing evidence to show that extracellular nucleotides regulate MSC functions and P2 receptor-mediated purinergic signalling plays an important role in such functional regulation. P2 receptors comprise ligand-gated ion channel P2X receptors and G-protein-coupled P2Y receptors. In this review, we provide an overview of the current understanding with respect to expression of the P2X and P2Y receptors in MSC and their roles in mediating extracellular nucleotide regulation of MSC proliferation, migration and differentiation. J. Cell. Physiol. 232: 287-297, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27403751 TI - Persistent Postoperative Pain: Pathophysiology, Risk Factors, and Prevention. AB - OBJECTIVE: Persistent postoperative pain (PPOP) is the second most common reason for a patient to seek care at a chronic pain center. Many of the patients seen with prolapse or incontinence are at risk for developing PPOP as a result of the surgeries done for these problems. The pathophysiology of this disabling pain disorder is well understood, and the risk factors are easy to identify. Once identified, perioperative interventions can be offered to attempt to prevent PPOP. METHODS AND RESULTS: Evaluation of articles obtained using a MEDLINE search involving chronic pain and PPOP, including prevalence, pathophysiology, and prevention was reviewed. The concept of central censitization and the key role it plays in chronic pain disorders were also reviewed. A history of chronic pain (anywhere) as well as findings of levator myalgia, allodynia, and hypertonic pelvic floor disorders is critical in identifying patients at risk for PPOP. CONCLUSIONS: Identification of patients at risk allows the clinician to educate the patient about the risk of PPOP and the various perioperative interventions that can be used to prevent its development. Further studies will be required to determine how effective these interventions are in patients undergoing surgery for incontinence and/or pelvic organ prolapse. PMID- 27403752 TI - Vesicosalpingo Fistula: A Case Presentation And Review of The Literature. AB - OBJECTIVES: To describe a case presentation and perform a review of the literature on vesicosalpingo fistulas. METHODS: An otherwise healthy 32 year-old patient was referred to urology with symptoms of persistent abdominal bloating and urine leakage from the vagina after abdominal conversion of laparoscopic hysterectomy. Two fistula tracts were identified in the bladder during preoperative cystoscopy. The tracts were cannulated with temporary ureteral catheters, and the patient underwent a robotic-assisted laparoscopic repair of a vesicosalpingo and a vesicovaginal fistula. RESULTS: The patient was discharged on the first postoperative day with an indwelling urinary catheter. A follow-up cystogram performed on the 14th postoperative day demonstrated no evidence of extravasation. There was no evidence of recurrence at a 4-month follow-up visit. This is the first reported robot-assisted laparoscopic repair of a vesicosalpingo fistula and the fifth reported case of a vesicosalpingo fistula in the literature. This is the first reported case of separate vesicosalpingo and vesicovaginal fistulas presenting concurrently in a single patient. CONCLUSIONS: This case presentation with 2 separate fistula tracts emanating from the bladder demonstrates the need to meticulously evaluate each individual fistula tract in order to successfully visualize and address all fistula tracts present in order to mitigate failures and the need for reoperation. PMID- 27403753 TI - Triathlete Risk of Pelvic Floor Disorders, Pelvic Girdle Pain, and Female Athlete Triad. AB - OBJECTIVES: Our primary objective was to describe the prevalence of pelvic floor disorders (PFDs), pelvic girdle pain (PGP), and the female athlete triad (disordered eating, menstrual irregularities, and osteoporosis) in a female triathlete population. We also evaluated for an association between these conditions. METHODS: We administered an online survey to women who self identified as female triathletes. Using validated questionnaires, Epidemiology of Prolapse and Incontinence Questionnaire and Pelvic Girdle Questionnaire, along with the female athlete triad questionnaire, we identified the prevalence of PFDs, PGP, and female athlete triad in this specific population. Demographic and exercise intensity were also queried to characterize these female triathletes. RESULTS: Three hundred eleven female triathletes responded to the Internet survey. There was a significant prevalence of PFDs with stress urinary incontinence and anal incontinence symptoms being most common (37.4% and 28%, respectively). Urgency urinary incontinence and pelvic organ prolapse were less common (16% and 5%, respectively). Stress urinary incontinence and pelvic organ prolapse were more common in parous triathletes (P = 0.001, P = 0.05). Pelvic girdle pain was noted in 18% of these triathletes but was not disabling. Twenty four percent of participants screened positive for at least 1 arm of the female athlete triad. No association was found between the female athlete triad and PFDs. CONCLUSIONS: Pelvic floor disorders are common and bothersome in female triathletes. Pelvic girdle pain, while present, does not limit these athletes from their training. These female triathletes may be at risk for the female athlete triad. Female triathletes may be at risk for both metabolic and PFDs and should be screened when identified. PMID- 27403754 TI - Utility of Postoperative Voiding Cystourethrogram After Lower Urinary Tract Repair. AB - OBJECTIVE: To characterize indications, timing, and results of voiding cystourethrogram (VCUG) studies after repair of the lower urinary tract and to determine how these results impact clinical management. METHODS: Women who underwent a VCUG between January 2006 and December 2012 were identified from a radiology billing database. After excluding women with abdominopelvic malignancies, demographic, clinical, index procedure and lower urinary tract repair characteristics, and VCUG results were analyzed. The impact of abnormal VCUG results on clinical management was assessed. RESULTS: Data were analyzed from 245 VCUG studies performed a median of 10 days (interquartile range, 8-12 days) after lower urinary tract repair. When classified by procedure type, VCUGs were performed a median of 9 days (7-13 days) after cystotomy repair, 11 days (10 12 days) after vesicovaginal fistula closure and 10 days (7-11 days) after diverticulectomy. Abnormal findings were noted in 7 of 245 (2.9%) VCUGs and included contrast extravasation (5/7) and urinary retention (2/7). In all cases, the abnormal VCUG prompted a change in clinical management with extended use of an indwelling catheter or intermittent self-catheterization in 1 case of urinary retention. CONCLUSIONS: Voiding cystourethrograms are a useful clinical tool in guiding the duration of Foley catheter use after lower urinary tract repair. Depending on clinical practice, VCUGs may reduce catheter-associated morbidity by facilitating earlier catheter removal and, in the minority of cases, may identify patients with incomplete postoperative healing. PMID- 27403755 TI - Comparison of Perioperative Complications by Route of Hysterectomy Performed for Benign Conditions. AB - OBJECTIVE: The aim of this study was to compare perioperative complications by route of hysterectomy before and after the introduction of robotic surgery. METHODS: This is an ancillary analysis of a multicenter, retrospective cohort study with historical controls through the Fellows' Pelvic Research Network. Hysterectomies performed for benign conditions were collected prior to introduction of the robot (prerobot) and the year after introduction of the robot (postrobot) at each institution. To obtain a representative annual case distribution for each institution, a maximum of 20 cases per month were selected using stratified random sampling. Patient demographics and intraoperative and postoperative complication data were collected. RESULTS: One thousand four hundred forty cases were included in this study, 732 in the prerobot and 708 in the postrobot period. Intraoperative complications in the prerobot group were highest in the abdominal group (7.4%) followed by vaginal (3.9%) and laparoscopic (3.7%) groups. Postoperative complications were higher in the vaginal (8.3%) and abdominal (7.4%) groups compared with laparoscopic (1.8%) groups (P = 0.03), because of a higher proportion of infections. In the postrobot period, intraoperative complications were lower in the vaginal (2.8%), robotic (3%), and laparoscopic (4.6%) groups compared with abdominal (10.8%) (P = 0.04). Postoperative complications were lowest in the vaginal (5.1%), laparoscopic (3.6%), and robotic (3%) approaches compared with the abdominal (13.9%) approach (P = 0.003). CONCLUSIONS: Vaginal hysterectomy has comparable rates of perioperative complications when compared with robotic and laparoscopic approaches and should be considered as a primary surgical approach in the growing armamentarium of minimally invasive approaches for hysterectomy for benign conditions. PMID- 27403756 TI - Outpatient Narcotic Use After Minimally Invasive Urogynecologic Surgery. AB - OBJECTIVES: To quantify outpatient narcotic use in the first 2 weeks after urogynecologic surgery. METHODS: Using a convenience sample, women who underwent minimally invasive urogynecologic surgery between May and October 2014 were contacted by telephone 2 weeks postoperatively and given a questionnaire regarding their postoperative pain experience. To quantify narcotic use, patients were asked to count the tablets remaining from their discharge narcotic prescription. Postoperative pain scores and pain expectations were also assessed. Women using more than 30 narcotics were in the top quartile for use; therefore, those using 30 or fewer versus more than 30 were compared. Logistic regression was used to identify independent factors associated with women in the top quartile for postoperative narcotic use. RESULTS: Fifty women were included in the study. Median number of narcotics used was 13 (interquartile range (IQR), 1 30) versus 40 (IQR, 35-60) prescribed. Compared to women who used 30 or fewer narcotics (n=38), those using more than 30 (n=12) more frequently were taking narcotics before surgery (13.2% vs 41.7%; P=0.03) and had a chronic pain diagnosis (15.8% vs 58.3%; P=0.003). Although pain scores were similar, women who took more than 30 narcotics more frequently reported their postoperative pain to be much worse or worse than expected (7.9% vs 33.3%; P=0.048). In logistic regression, chronic pain remained the only factor associated with using more than 30 narcotics (odds ratio, 7.36; 95% confidence interval, 1.00-54.03; P=0.0496). CONCLUSIONS: Women used one third of the narcotics they were prescribed after minimally invasive urogynecologic surgery. These data may be useful for establishing narcotic prescription guidelines. PMID- 27403757 TI - Workforce Analysis of Female Pelvic Medicine and Reconstructive Surgery, 2015 to 2045. AB - OBJECTIVES: The aim of this study was to assess how the projected increase in prevalence of pelvic floor disorders (PFDs) will impact the number of patients per female pelvic medicine and reconstructive surgery (FPMRS) subspecialist between 2015 and 2045. METHODS: We performed a workforce analysis of FPMRS subspecialists in the United States by developing a model to predict the number of FPMRS subspecialists in 5-year increments from 2015 to 2045. Our model allowed for selection of the number of current FPMRS subspecialists, the number and sex of new FPMRS subspecialists added per year, and retirement age of FPMRS subspecialists. The number of women with PFDs from 2015 to 2045 was then predicted by applying published, age-specific prevalence rates to the 2012 US Census Projections for women aged 20 years or older. For our primary outcome, we divided the projected number of patients by the projected number of FPMRS subspecialists every 5 years from 2015 to 2045. RESULTS: The model predicts the number of FPMRS subspecialists will increase from 1133 to 1514 with a sex shift from 46% female to 81% female between 2015 and 2045. The number of women with >=1 PFD is predicted to increase from 31.4 million in 2015 to 41.9 million in 2045. For our primary outcome, the number of patients per FPMRS subspecialist is projected to range from 27,870 in 2015 to 27,650 in 2045. CONCLUSIONS: The current ratio of patients per FPMRS subspecialist appears high and is predicted to remain near current levels over the next 30 years. These projections support the need for continued training of physicians skilled in treating PFDs. PMID- 27403758 TI - One-Year Outcomes After Minimally Invasive Sacrocolpopexy. AB - OBJECTIVE: The primary aim of this study was to report anatomic, symptom, and quality of life outcomes in women with symptomatic stage 2 or greater prolapse 1 year after randomization to robotic and laparoscopic sacrocolpopexy. METHODS: This is a planned ancillary analysis of the Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies trial, a randomized comparative effectiveness trial comparing costs and outcomes of robotic and laparoscopic sacrocolpopexy at 2 academic medical centers. At baseline and 1 year after surgery, women underwent standardized assessment including validated subjective pelvic floor outcomes and physical examination with prolapse assessment. RESULTS: Sixty six (85%) of 78 randomized participants completed 1-year follow-up: 33 (87%) of 38 in the laparoscopic arm and 33 (83%) of 40 in the robotic arm (P = 0.59). Ninety-seven percent (32/33) in the laparoscopic group and 100% (33/33) in the robotic arm considered that their prolapse symptoms improved (P = 0.999). The cohort had significant improvement in all pelvic floor symptom and quality of life measures, which did not differ by treatment arm. Of women who were sexually active at 1 year, sexual function improved in both cohorts. No new serious adverse events, including mesh exposure or reoperation for prolapse, were identified between 6 months and 1 year after surgery. No women had a sacrocolpopexy mesh complication or reoperation for mesh exposure. CONCLUSIONS: Minimally invasive sacrocolpopexy is associated with significant improvement in pelvic floor symptoms, anatomy, and sexual function. In addition, mesh exposure rates with lightweight polypropylene mesh seem to be lower than those reported with multifilament and heavier polypropylene mesh. PMID- 27403759 TI - Delayed Diagnosis of Vesicouterine Fistula After Treatment for Mixed Urinary Incontinence: Menstrual Cup Management and Diagnosis. AB - INTRODUCTION: A vesicouterine fistula is a rare form of urogenital fistula, yet there is increasing prevalence in the United States because of the rising rate of cesarean deliveries. Vesicouterine fistulas have various presentations including menouria, hematuria, or urinary incontinence. CASE PRESENTATION: A 39-year-old multiparous woman presented with urine leakage after her third cesarean delivery. She had been treated for mixed urinary incontinence with overactive bladder medications and a midurethral sling with continued complaints of urine leakage. The patient noticed her symptoms of urine leakage improved during menses when she used a menstrual cup. After confirmation of vesicouterine fistula, the patient underwent robotic-assisted surgery and her symptoms of insensible urine leakage resolved. CONCLUSIONS: When evaluating women with urinary incontinence and a history of cesarean deliveries, use of menstrual cup may aid in the diagnosis of vesicouterine fistula. Robotic-assisted laparoscopic repair with tissue interposition flap is an efficacious minimally invasive method for treatment of vesicouterine fistula. PMID- 27403760 TI - A New Quantitative Method for Evaluating Dry Powder Inhalation Efficiency in Asthma Patients. AB - PURPOSE: Many methods have been developed to evaluate dry powder inhalation techniques and their efficiency for disease control in asthma patients. However, it is difficult to apply these methods to clinical practice and research. In this study, we introduce a simple new method that can be applied to dry powder inhalation techniques to evaluate their efficiency in clinical practice. METHODS: Twenty volunteers were recruited to evaluate the reliability of this new method. One hundred one asthma patients who met the inclusion criteria participated in this study. A dark cloth covered the outlet of the inhaler during dry powder inhalation. The image formed by the inhalation process was evaluated using analysis software and converted into integrated optical density (IOD). Inhalation techniques were scored before and after inhalation technique training, and asthma control was evaluated using the Asthma Control Questionnaire (ACQ) before inhalation technique training. RESULTS: The relative standard deviation of IOD ranged from 3.8% to 7.8%. In patients with or without inhaler prior use, both the IOD and inhalation technique scores improved significantly after inhalation technique training (p < 0.05). Inhalation technique scores were positively correlated with IOD before (r = 0.80, p < 0.001) and after inhalation technique training (r = 0.52, p < 0.001). In patients with prior inhaler experience, ACQ results were negatively correlated with inhalation technique scores (r = -0.44; p < 0.05) and IOD (r = -0.52; p < 0.05). CONCLUSION: The results from this study demonstrated that this quantitative method is equivalent to traditional methods for dry powder inhalation evaluation. This study also indicated that training significantly improved the inhalation technique and efficiency in asthma patients with or without prior inhaler use. PMID- 27403761 TI - The importance of correcting for variable probe-sample interactions in AFM-IR spectroscopy: AFM-IR of dried bacteria on a polyurethane film. AB - AFM-IR is a combined atomic force microscopy-infrared spectroscopy method that shows promise for nanoscale chemical characterization of biological-materials interactions. In an effort to apply this method to quantitatively probe mechanisms of microbiologically induced polyurethane degradation, we have investigated monolayer clusters of ~200 nm thick Pseudomonas protegens Pf-5 bacteria (Pf) on a 300 nm thick polyether-polyurethane (PU) film. Here, the impact of the different biological and polymer mechanical properties on the thermomechanical AFM-IR detection mechanism was first assessed without the additional complication of polymer degradation. AFM-IR spectra of Pf and PU were compared with FTIR and showed good agreement. Local AFM-IR spectra of Pf on PU (Pf-PU) exhibited bands from both constituents, showing that AFM-IR is sensitive to chemical composition both at and below the surface. One distinct difference in local AFM-IR spectra on Pf-PU was an anomalous ~4* increase in IR peak intensities for the probe in contact with Pf versus PU. This was attributed to differences in probe-sample interactions. In particular, significantly higher cantilever damping was observed for probe contact with PU, with a ~10* smaller Q factor. AFM-IR chemical mapping at single wavelengths was also affected. We demonstrate ratioing of mapping data for chemical analysis as a simple method to cancel the extreme effects of the variable probe-sample interactions. PMID- 27403762 TI - Mass spectrometric epitope mapping. AB - Mass spectrometric epitope mapping has become a versatile method to precisely determine a soluble antigen's partial structure that directly interacts with an antibody in solution. Typical lengths of investigated antigens have increased up to several 100 amino acids while experimentally determined epitope peptides have decreased in length to on average 10-15 amino acids. Since the early 1990s more and more sophisticated methods have been developed and have forwarded a bouquet of suitable approaches for epitope mapping with immobilized, temporarily immobilized, and free-floating antibodies. While up to now monoclonal antibodies have been mostly used in epitope mapping experiments, the applicability of polyclonal antibodies has been proven. The antibody's resistance towards enzymatic proteolysis has been of key importance for the two mostly applied methods: epitope excision and epitope extraction. Sample consumption has dropped to low pmol amounts on both, the antigen and the antibody. While adequate in solution sample handling has been most important for successful epitope mapping, mass spectrometric analysis has been found the most suitable read-out method from early on. The rapidity by which mass spectrometric epitope mapping nowadays is executed outperforms all alternative methods. Thus, it can be asserted that mass spectrometric epitope mapping has reached a state of maturity, which allows it to be used in any mass spectrometry laboratory. After 25 years of constant and steady improvements, its application to clinical samples, for example, for patient characterization and stratification, is anticipated in the near future. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:229-241, 2018. PMID- 27403763 TI - Gold Sulfinyl Mesoionic Carbenes: Synthesis, Structure, and Catalytic Activity. AB - Gold mesoionic carbenes having a chiral sulfoxide group attached to the C4 position of the five membered ring have been prepared and tested as catalysts in the cycloisomerization of enynes. These new catalysts are very efficient, with the sulfoxide moiety playing a key role in their activity and the N1-substituent in control of the regioselectivity of these processes. PMID- 27403764 TI - Accumulation of Palmitoylcarnitine and Its Effect on Pro-Inflammatory Pathways and Calcium Influx in Prostate Cancer. AB - BACKGROUND: Acylcarnitines are intermediates of fatty acid oxidation and accumulate as a consequence of the metabolic dysfunction resulting from the insufficient integration between beta-oxidation and the tricarboxylic acid (TCA) cycle. The aim of this study was to investigate whether acylcarnitines accumulate in prostate cancer tissue, and whether their biological actions could be similar to those of dihydrotestosterone (DHT), a structurally related compound associated with cancer development. METHODS: Levels of palmitoylcarnitine (palcar), a C16:00 acylcarnitine, were measured in prostate tissue using LC-MS/MS. The effect of palcar on inflammatory cytokines and calcium (Ca(2+) ) influx was investigated in in vitro models of prostate cancer. RESULTS: We observed a significantly higher level of palcar in prostate cancerous tissue compared to benign tissue. High levels of palcar have been associated with increased gene expression and secretion of the pro-inflammatory cytokine IL-6 in cancerous PC3 cells, compared to normal PNT1A cells. Furthermore, we found that high levels of palcar induced a rapid Ca(2+) influx in PC3 cells, but not in DU145, BPH-1, or PNT1A cells. This pattern of Ca(2+) influx was also observed in response to DHT. Through the use of whole genome arrays we demonstrated that PNT1A cells exposed to palcar or DHT have a similar biological response. CONCLUSIONS: This study suggests that palcar might act as a potential mediator for prostate cancer progression through its effect on (i) pro-inflammatory pathways, (ii) Ca(2+) influx, and (iii) DHT-like effects. Further studies need to be undertaken to explore whether this class of compounds has different biological functions at physiological and pathological levels. Prostate 76:1326-1337, 2016. (c) 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID- 27403766 TI - Highly Efficient Access to Both Geometric Isomers of Silyl Enol Ethers: Sequential 1,2-Brook/Wittig Reactions. AB - Novel sequential 1,2-Brook/Wittig reactions were developed for the preparation of silyl enol ethers. This method enables highly selective preparation of both geometric isomers of glyoxylate silyl enol ethers, using aldehydes (E-selective) and tosylimines (Z-selective) as a Wittig electrophile. The salt-free conditions of this reaction system are likely to be advantageous for switching the selectivity. The optimal reaction conditions and generality of the reaction were investigated, and plausible explanations for the observed selectivity were also discussed. PMID- 27403765 TI - Distortion correction in diffusion-weighted imaging of the breast: Performance assessment of prospective, retrospective, and combined (prospective + retrospective) approaches. AB - PURPOSE: To compare the effectiveness of prospective, retrospective, and combined (prospective + retrospective) EPI distortion correction methods in bilateral breast diffusion-weighted imaging (DWI) scans. METHODS: Five healthy female subjects underwent an axial bilateral breast DWI exam with and without prospective B0 inhomogeneity correction using slice-by-slice linear shimming. In each case, an additional b=0 DWI scan was performed with the polarity of the phase-encoding gradient reversed, to generate an estimated B0 map; this map or a separately acquired B0 map was used for retrospective correction, either alone or in combination with the prospective correction. The alignment between an undistorted, anatomical reference scan with similar contrast and the corrected b=0 DWI images with different correction schemes was assessed. RESULTS: The average cross-correlation coefficient between the DWI images and the anatomical reference scan was increased from 0.82 to 0.92 over the five volunteers when combined prospective and retrospective distortion correction was applied. Furthermore, such correction substantially reduced patient-to-patient variation of the image alignment and the variability of the average apparent diffusion coefficient in normal glandular tissue. CONCLUSION: Combined prospective and retrospective distortion correction can provide an efficient way to reduce susceptibility-induced image distortions and enhance the reliability of breast DWI exams. Magn Reson Med 78:247-253, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27403767 TI - Prognostic value of bacterial infection in acute and chronic liver failure. PMID- 27403768 TI - Reply to External validation of an individual prognostic calculator after trans arterial chemo-embolization for hepatocellular carcinoma. PMID- 27403769 TI - Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children. AB - Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9+/ 1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability. PMID- 27403770 TI - Light Transmission Aggregometry Does Not Correlate With the Severity of delta Granule Platelet Storage Pool Deficiency. AB - Delta-granule platelet storage pool deficiency (delta-PSPD) is a poorly studied bleeding diathesis resulting from either decreased granule content or decreased average number of platelet delta-granules. Light transmission aggregometry (LTA) is commonly used to evaluate for delta-PSPD and platelet electron microscopy (EM) is used to confirm the diagnosis. Currently, little data exist examining the relationship between the likelihood of abnormal platelet aggregation findings, severity of delta-granule deficiency on platelet EM, and severity of bleeding symptoms in patients with delta-PSPD. Patients diagnosed with delta-PSPD by platelet EM who also underwent LTA testing were identified at a single institution for correlation between severity of bleeding, average number of platelet delta-granules, and number of agonist abnormalities on LTA. No statistically significant association was identified between the average number of delta-granules per platelet and likelihood of an abnormal LTA. LTA abnormalities were quite varied and only 50% diagnosed with delta-PSPD on EM had abnormal aggregation testing. Also, no correlation was seen between the number of clinical bleeding symptoms, number of average delta-granules per platelet, and the number of LTA agonist abnormalities. Our findings highlight the difficulties inherent in the laboratory evaluation of platelet function. PMID- 27403771 TI - Recipient-derived EBV-positive Monomorphic Plasmacytoma Type Posttransplant Lymphoproliferative Disorder After Allogeneic Stem Cell Transplant for Severe Aplastic Anemia: A Case Report. AB - Monomorphic plasmacytoma-type posttransplant lymphoproliferative disorder (PTLD) has not been reported after pediatric hematopoietic stem cell transplantation. We present a child with hepatitis-associated severe aplastic anemia who underwent an unrelated allogeneic hematopoietic stem cell transplantation and subsequently developed graft failure and an Epstein-Barr virus-positive monomorphic plasmacytoma-type PTLD of recipient origin. Despite broad-spectrum antimicrobials, weaning immunosuppression, rituximab administration, and a stem cell boost she died from complications of PTLD and a fungal pulmonary infection on day +78. PMID- 27403772 TI - A Rare Case of Primary Myelofibrosis in a 14-Year-Old Patient With Congenital Asplenia. AB - Primary myelofibrosis (PMF) is rarely diagnosed in children, and in most cases in children younger than 3 years old. Pediatric PMF generally follows a benign course and is usually managed supportively with blood transfusions and prophylactic antibiotics for infections. We present a case of a 17-year-old girl diagnosed with PMF at the age of 14 years. A computed tomography scan performed at the time of an appendectomy showed congenital asplenism. To our knowledge, this is only the third case of myelofibrosis and congenital asplenism to be reported in the literature. Whether asplenism contributed to the development of myelofibrosis is not known. PMID- 27403773 TI - Factors Affecting the Upper Limit of the Methotrexate (MTX) CSF Levels Achievable in Children With Brain Tumors Treated With High-dose Intravenous MTX. AB - BACKGROUND: Little has been published in the medical literature on serum and cerebrospinal fluid (CSF) methotrexate (MTX) levels in children with brain tumors. METHODS: Matched 24-hour serum and CSF MTX levels were studied after 113 treatments in 35 brain tumors patients. RESULTS: A correlation between the 24 hour serum levels of MTX and MTX dosage was observed after 113 treatments in all 35 patients (r=0.39, P<0.001) but no statistical difference was found between CSF MTX levels in the irradiated and nonirradiated groups (P=0.12). Nonirradiated children received a lower dose of MTX (12.3+/-4.8 cf 14.8+/-3.7) (P=0.002). The 24-hour MTX CSF levels of these 2 groups were also found to be different (the nonirradiated group 7.6+/-9.8 cf 12.5+/-0.15.3). Using the Levene test for variances we found that these variances were not equal and therefore we used the Welch test which resulted in a P-value of 0.04. However, when an analysis of covariance was performed looking at evidence of CSF disease and MTX dose the radiation difference was no longer significant (P=0.15). The 24-hour CSF MTX levels in children without evidence of active CSF disease were consistently lower than those with active disease using a mixed-model analysis (P=0.002). Although a 24-hour CSF MTX level of at least 1 MUM was observed after infusions of >5 g/m MTX in previously irradiated children and after infusion of >=10 g/m in nonirradiated children this difference did not reach statistical significance. CSF MTX levels plateau at doses of MTX 15 g/m putting in doubt the value of administering even higher doses of MTX. CONCLUSIONS: The 24-hour MTX CSF levels are higher in patients with active CSF disease. Doses of <10 gm/m in children with brain tumors may not achieve a guaranteed 24-hour MTX CSF level of 1 MUM. There may be little value in a given dose of >15 g/m MTX as CSF levels plateau at this dose. PMID- 27403774 TI - Diffuse Adenomyomatosis of the Gallbladder in a Child. AB - Adenomyomatosis of the gallbladder (ADMG) is characterized by proliferation of the mucosal epithelium and hypertrophy of the muscularis. ADMG is predominantly diagnosed by using ultrasonography. Although ADMG is benign in nature, lithiasis, and chronic inflammation secondary to it may lead to dysplastic changes and cancer. Mucosal invagination through the hypertrophied muscularis results in large intramural diverticula or sinus tracts which are visible at radiology, known as Rokitansky-Aschoff sinuses. Histologically, ADMG manifests with hyperplasia of the muscular layer and proliferation of mucosal glandular tissues. We describe a case of ADMG in an 8-year-old girl presenting with recurrent abdominal pain. Diagnosis was made using ultrasound, and the condition was successfully treated with open cholecystectomy. Ultrasound scanning in children presenting with recurrent abdominal pain may lead to more accurate diagnosis of ADMG during childhood. PMID- 27403775 TI - Rapid Neurological Recovery Following Partial Surgical Resection of Spinal Glioblastoma Multiforme in a Pediatric Patient Presenting With Complete Paraplegia. AB - Pediatric spinal cord glioblastoma multiforme is a rare entity with a poor prognosis often presenting with lower extremity weakness or paralysis. Previous literature suggests that aggressive surgical resection may provide overall survival benefit; however, there is limited concurrent analysis demonstrating neurological recovery following surgical resection. We report the case of a 9 year-old boy who presented with complete paraplegia and regained the ability to ambulate independently following subtotal surgical resection, radiation, and chemotherapy. The case demonstrates the balance between meaningful neurological recovery and overall survival when deciding on the extent of resection in cases of pediatric spinal glioblastoma multiforme. PMID- 27403776 TI - Outcomes Following Bone Marrow Transplantation in Children With Accelerated Phase or Blast Crisis Chronic Myelogenous Leukemia in the Era of Tyrosine Kinase Inhibitors. AB - The management of chronic myelogenous leukemia (CML) in children changed dramatically with the introduction of tyrosine kinase inhibitors (TKIs). Unfortunately, outcomes for patients presenting in an advanced stage-accelerated phase or blast crisis CML-continues to be poor, requiring chemotherapy and allogeneic hematopoietic stem cell transplant (HSCT) to attempt cure. Integration of TKIs in the therapy of advanced CML is still an area of active investigation. There are little published data on TKI use in children with advanced stage CML. We performed a retrospective review of all children treated at our institution between January 1, 2010 and June 30, 2013, and identified 5 children, age 12 to 18 years, with advanced stage CML. All patients were treated with a TKI before HSCT and TKIs were restarted post-HSCT in 4/5 with a goal of continuing until 2 years posttransplant. At time of HSCT all were in a morphologic and cytogenetic remission; 1 patient had also achieved molecular remission. All patients are alive and in molecular remission at an average of 38 months (range, 14 to 51 mo) following transplant. Our experience indicates that TKIs are safe and well tolerated in children both pretransplant and posttransplant and may improve outcomes in this aggressive disease. PMID- 27403777 TI - Sensitivity Analysis of a Physiologically Based Pharmacokinetic Model Used for Treatment Planning in Peptide Receptor Radionuclide Therapy. AB - The aim of this work was to evaluate the sensitivity of time-integrated activity coefficients (TIACs) on the erroneously chosen prior knowledge in a physiologically based pharmacokinetic (PBPK) model used for treatment planning in peptide receptor radionuclide therapy (PRRT). Parameters of the PBPK model were fitted to the biokinetic data of 15 patients after the injection of (111)In DTPAOC. The fittings were performed using fixed parameter values taken from literature as prior knowledge (reference case, Ref). The fixed parameters were gender, physical information (e.g., body weight), dissociation rate koff, dissociation constant KD, fraction of blood flow, and spleen and liver volumes. The fittings were repeated with changed fixed parameters (Changed). The relative deviations (RDs) of TIACs calculated from Changed and Ref were analyzed for kidneys, tumor, liver, spleen, remainder, whole body, and serum. A changed koff has the largest effect on RD, the largest RD values were found for changed koff = 0.001 L/min: RDkidneys = (3 +/- 3)%, RDtumor = (0.5 +/- 4)%, RDliver = (6 +/- 9)%, RDspleen = (5 +/- 5)%, RDremainder = (2 +/- 31)%, RDserum = (-4 +/- 25)%, and RDwholebody = (3 +/- 16)%. For other changed parameters, the maximum RDs were <1%. The calculation of organ TIACs in PRRT using the PBPK model was little affected by assigning wrong prior knowledge to the evaluated patients. The calculation of bone marrow-absorbed doses could be affected by the inaccurate TIACs of serum and remainder in the case of an inadequate koff. PMID- 27403778 TI - Marker-aided Incorporation of Xa38, a Novel Bacterial Blight Resistance Gene, in PB1121 and Comparison of its Resistance Spectrum with xa13 + Xa21. AB - Basmati rice is preferred internationally because of its appealing taste, mouth feel and aroma. Pusa Basmati 1121 (PB1121) is a widely grown variety known for its excellent grain and cooking quality in the international and domestic market. It contributes approximately USD 3 billion to India's forex earning annually by being the most traded variety. However, PB1121 is highly susceptible to bacterial blight (BB) disease. A novel BB resistance gene Xa38 was incorporated in PB1121 from donor parent PR114-Xa38 using a modified marker-assisted backcross breeding (MABB) scheme. Phenotypic selection prior to background selection was instrumental in identifying the novel recombinants with maximum recovery of recurrent parent phenome. The strategy was effective in delimiting the linkage drag to <0.5 mb upstream and <1.9 mb downstream of Xa38 with recurrent parent genome recovery upto 96.9% in the developed NILs. The NILs of PB1121 carrying Xa38 were compared with PB1121 NILs carrying xa13 + Xa21 (developed earlier in our lab) for their resistance to BB. Both NILs showed resistance against the Xoo races 1, 2, 3 and 6. Additionally, Xa38 also resisted Xoo race 5 to which xa13 + Xa21 was susceptible. The PB1121 NILs carrying Xa38 gene will provide effective control of BB in the Basmati growing region. PMID- 27403779 TI - Getting the whole picture: High content screening using three-dimensional cellular model systems and whole animal assays. AB - Phenotypic or High Content Screening (HCS) is becoming more widely used for primary screening campaigns in drug discovery. Currently the vast majority of HCS campaigns are using cell lines grown in well-established monolayer cultures (2D tissue culture). There is widespread recognition that the more biologically relevant 3D tissue culture technologies such as spheroids and organoids and even whole animal assays will eventually be run as primary HCS. Upgrading the IT infrastructure to cope with the increase in data volumes requires investments in hardware (and software) and this will be manageable. However, the main bottleneck for the effective adoption and use of 3D tissue culture and whole animal assays in HCS is anticipated to be the development of software for the analysis of 3D images. In this review we summarize the current state of the available software and how they may be applied to analyzing 3D images obtained from a HCS campaign. (c) 2016 International Society for Advancement of Cytometry. PMID- 27403780 TI - Qubit lattice coherence induced by electromagnetic pulses in superconducting metamaterials. AB - Quantum bits (qubits) are at the heart of quantum information processing schemes. Currently, solid-state qubits, and in particular the superconducting ones, seem to satisfy the requirements for being the building blocks of viable quantum computers, since they exhibit relatively long coherence times, extremely low dissipation, and scalability. The possibility of achieving quantum coherence in macroscopic circuits comprising Josephson junctions, envisioned by Legett in the 1980's, was demonstrated for the first time in a charge qubit; since then, the exploitation of macroscopic quantum effects in low-capacitance Josephson junction circuits allowed for the realization of several kinds of superconducting qubits. Furthermore, coupling between qubits has been successfully achieved that was followed by the construction of multiple-qubit logic gates and the implementation of several algorithms. Here it is demonstrated that induced qubit lattice coherence as well as two remarkable quantum coherent optical phenomena, i.e., self-induced transparency and Dicke-type superradiance, may occur during light pulse propagation in quantum metamaterials comprising superconducting charge qubits. The generated qubit lattice pulse forms a compound "quantum breather" that propagates in synchrony with the electromagnetic pulse. The experimental confirmation of such effects in superconducting quantum metamaterials may open a new pathway to potentially powerful quantum computing. PMID- 27403781 TI - Torsional strength of computer-aided design/computer-aided manufacturing fabricated esthetic orthodontic brackets. AB - OBJECTIVE: To fabricate orthodontic brackets from esthetic materials and determine their fracture resistance during archwire torsion. MATERIALS AND METHODS: Computer-aided design/computer-aided manufacturing technology (Cerec inLab, Sirona) was used to mill brackets with a 0.018 * 0.025-inch slot. Materials used were Paradigm MZ100 and Lava Ultimate resin composite (3M ESPE), Mark II feldspathic porcelain (Vita Zahnfabrik), and In-Ceram YZ zirconia (Vita Zahnfabrik). Ten brackets of each material were subjected to torque by a 0.018 * 0.025-inch stainless steel archwire (G&H) using a specially designed apparatus. The average moments and degrees of torsion necessary to fracture the brackets were determined and compared with those of commercially available alumina brackets, Mystique MB (Dentsply GAC). RESULTS: The YZ brackets were statistically significantly stronger than any other tested material in their resistance to torsion (P < .05). The mean torques at failure ranged from 3467 g.mm for Mark II to 11,902 g.mm for YZ. The mean torsion angles at failure ranged from 15.3 degrees to 40.9 degrees . CONCLUSION: Zirconia had the highest torsional strength among the tested esthetic brackets. Resistance of MZ100 and Lava Ultimate composite resin brackets to archwire torsion was comparable to commercially available alumina ceramic brackets. PMID- 27403782 TI - SGLT2 inhibitors and renal function. PMID- 27403783 TI - Onzetra Xsail--sumatriptan nasal powder. PMID- 27403784 TI - Buprenorphine implants (Probuphine) for opioid dependence. PMID- 27403785 TI - Brivaracetam (Briviact) for epilepsy. PMID- 27403786 TI - Asfotase alfa (Strensiq) for hypophosphatasia. PMID- 27403787 TI - In brief: Cabozantinib (Cabometyx) for advanced renal cell carcinoma. PMID- 27403789 TI - Recent developments in free-radical-promoted C-Si formation via selective C-H/Si H functionalization. AB - As important and valuable alternatives to transition-metal-catalysis, free radical strategies for C-Si bond construction via selective C-H/Si-H functionalization have been developed recently. These new reactions along with their suggested mechanisms are summarized and discussed here. PMID- 27403788 TI - Low-grade endotoxemia and clotting activation in the early phase of pneumonia. AB - BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is associated with an increased risk of arterial and venous thrombosis but the underlying pathophysiological mechanisms are still unclear. We investigated if, in patients with CAP, a pro-thrombotic state does exist and its relationship with serum levels of endotoxins. METHODS: A total of 104 consecutive patients with CAP were prospectively recruited and followed up until discharge. At admission and at discharge, serum endotoxins, systemic markers of clotting activation and zonulin, a marker of gut permeability, were analysed. Hospitalized patients matched for gender, age and comorbidities but without infections were used as control. RESULTS: At admission, CAP patients showed higher plasma levels of F1+2 , a marker of thrombin generation (P = 0.023), and lower levels of protein C (PC; P < 0.001) and activated PC (aPC) (P < 0.001) compared with controls. At discharge, plasma levels of both PC and aPC significantly increased while F1+2 significantly decreased (P < 0.001). Baseline serum endotoxins and zonulin were higher in CAP patients than controls (P < 0.001) and significantly decreased at discharge; a significant correlation between serum endotoxins and zonulin was detected (R = 0.575; P < 0.001) CONCLUSION: This study provides the first evidence that CAP patients disclose an ongoing pro-thrombotic state and suggests a role for endotoxemia in determining enhanced thrombin generation. PMID- 27403790 TI - Footprints reveal direct evidence of group behavior and locomotion in Homo erectus. AB - Bipedalism is a defining feature of the human lineage. Despite evidence that walking on two feet dates back 6-7 Ma, reconstructing hominin gait evolution is complicated by a sparse fossil record and challenges in inferring biomechanical patterns from isolated and fragmentary bones. Similarly, patterns of social behavior that distinguish modern humans from other living primates likely played significant roles in our evolution, but it is exceedingly difficult to understand the social behaviors of fossil hominins directly from fossil data. Footprints preserve direct records of gait biomechanics and behavior but they have been rare in the early human fossil record. Here we present analyses of an unprecedented discovery of 1.5-million-year-old footprint assemblages, produced by 20+ Homo erectus individuals. These footprints provide the oldest direct evidence for modern human-like weight transfer and confirm the presence of an energy-saving longitudinally arched foot in H. erectus. Further, print size analyses suggest that these H. erectus individuals lived and moved in cooperative multi-male groups, offering direct evidence consistent with human-like social behaviors in H. erectus. PMID- 27403802 TI - Women's experiences of dating after breast cancer. AB - This study examined women's experiences of romantically dating after breast cancer. Semistructured interviews were conducted with 22 female breast cancer survivors who attempted to form new relationships post-breast cancer. Interview transcripts were analyzed using grounded theory methodology. We identified an overarching theme of "navigating the breast cancer dating journey," comprising seven themes including women's decision to consider dating; ability/desire to commence a new relationship; cancer-related disclosure; changes to intimacy and sexuality; body image difficulties; changing values; and trusting a new partner. Future research should empirically determine factors predicting a woman's ability to form a romantic relationship after breast cancer. PMID- 27403803 TI - Thickness Considerations of Two-Dimensional Layered Semiconductors for Transistor Applications. AB - Layered two-dimensional semiconductors have attracted tremendous attention owing to their demonstrated excellent transistor switching characteristics with a large ratio of on-state to off-state current, Ion/Ioff. However, the depletion-mode nature of the transistors sets a limit on the thickness of the layered semiconductor films primarily determined by a given Ion/Ioff as an acceptable specification. Identifying the optimum thickness range is of significance for material synthesis and device fabrication. Here, we systematically investigate the thickness-dependent switching behavior of transistors with a wide thickness range of multilayer-MoS2 films. A difference in Ion/Ioff by several orders of magnitude is observed when the film thickness, t, approaches a critical depletion width. The decrease in Ion/Ioff is exponential for t between 20 nm and 100 nm, by a factor of 10 for each additional 10 nm. For t larger than 100 nm, Ion/Ioff approaches unity. Simulation using technical computer-aided tools established for silicon technology faithfully reproduces the experimentally determined scaling behavior of Ion/Ioff with t. This excellent agreement confirms that multilayer MoS2 films can be approximated as a homogeneous semiconductor with high surface conductivity that tends to deteriorate Ion/Ioff. Our findings are helpful in guiding material synthesis and designing advanced field-effect transistors based on the layered semiconductors. PMID- 27403804 TI - Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications. AB - The spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high throughput assay to identify potential rosette-disrupting compounds. A pilot screen of 2693 compounds identified Malaria Box compound MMV006764 as a potential candidate. Although it reduced rosetting by a modest 20%, MMV006764 was validated to be similarly effective against both blood group O and A rosettes of three laboratory parasite lines. Coupled with its antiplasmodial activity and drug likeness, MMV006764 represents the first small-molecule compound that disrupts rosetting and could potentially be used in a resource-limited setting to treat patients deteriorating rapidly from malaria complications. Such dual-action drugs that simultaneously restore microcirculation and reduce parasite load could significantly reduce malaria morbidity and mortality. PMID- 27403805 TI - Investigating the Function of Coronin A in the Early Starvation Response of Dictyostelium discoideum by Aggregation Assays. AB - Dictyostelium discoideum amoeba are found in soil, feeding on bacteria. When food sources become scarce, they secrete factors to initiate a multicellular development program, during which single cells chemotax towards aggregation centers(1-4). This process is dependent on the release of cyclic adenosine monophosphate (cAMP)(5). cAMP is produced in waves through the concerted action of adenylate cyclase and phosphodiesterases, and binds to G protein-coupled cAMP receptors(6,7). A widely used assay to analyze the mechanisms involved in the developmental cycle of the lower eukaryote Dictyostelium discoideum is based on the observation of cell aggregation in submerged conditions(8,9). This protocol describes the analysis of the role of coronin A in the developmental cycle by starvation in tissue-culture plates submerged in balanced salt solution (BSS)(10). Coronin A is a member of the widely conserved protein family of coronins that have been implicated in a wide variety of activities(11,12). Dictyostelium cells lacking coronin A are unable to form multicellular aggregates, and this defect can be rescued by supplying pulses of cAMP, suggesting that coronin A acts upstream of the cAMP cascade(10). The techniques described in these studies provide robust tools to investigate functions of proteins during the initial stages of the developmental cycle of Dictyostelium discoideum upstream of the cAMP cascade. Therefore, utilizing this aggregation assay may allow the further study of coronin A function and advance our understanding of coronin biology. PMID- 27403806 TI - X-ray detection with zinc-blende (cubic) GaN Schottky diodes. AB - The room temperature X-ray responses as functions of time of two n type cubic GaN Schottky diodes (200 MUm and 400 MUm diameters) are reported. The current densities as functions of time for both diodes showed fast turn-on transients and increases in current density when illuminated with X-ray photons of energy up to 35 keV. The diodes were also electrically characterized: capacitance, implied depletion width and dark current measurements as functions of applied bias at room temperature are presented. At -5 V reverse bias, the capacitances of the diodes were measured to be (84.05 +/- 0.01) pF and (121.67 +/- 0.02) pF, respectively. At -5 V reverse bias, the dark current densities of the diodes were measured to be (347.2 +/- 0.4) mA cm(-2) and (189.0 +/- 0.2) mA cm(-2), respectively. The Schottky barrier heights of the devices (0.52 +/- 0.07) eV and (0.63 +/- 0.09) eV, respectively, were extracted from the forward dark current characteristics. PMID- 27403807 TI - Non-responsiveness to intravitreal aflibercept treatment in neovascular age related macular degeneration: implications of serous pigment epithelial detachment. AB - The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients. PMID- 27403808 TI - Robotic surgery for upper gastrointestinal cancer: Current status and future perspectives. AB - Robotic surgery with the da Vinci Surgical System has been increasingly applied in a wide range of surgical specialties, especially in urology and gynecology. However, in the field of upper gastrointestinal (GI) tract, the da Vinci Surgical System has yet to be standard as a result of a lack of clear benefits in comparison with conventional minimally invasive surgery. We have been carrying out robotic gastrectomy and esophagectomy for operable patients with resectable upper GI malignancies since 2009, and have demonstrated the potential advantages of the use of the robot in possibly reducing postoperative local complications including pancreatic fistula following gastrectomy and recurrent laryngeal nerve palsy after esophagectomy, even though there have been a couple of problems to be solved including longer duration of operation and higher cost. The present review provides updates on robotic surgery for gastric and esophageal cancer based on our experience and review of the literature. PMID- 27403809 TI - Expression of osteoprotegerin and its ligands, RANKL and TRAIL, in rheumatoid arthritis. AB - Osteoprotegerin (OPG), receptor activator of nuclear factor-KappaB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been involved in rheumatoid arthritis (RA) pathophysiology. In this study, we assessed messenger RNA (mRNA) expression of these molecules by qPCR in peripheral blood from 26 patients with RA (12 of them with ischemic heart disease -IHD) and 10 healthy controls. Correlation coefficients between OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics were also evaluated. Whereas OPG and OPG/TRAIL ratio expression were significantly increased in RA patients compared to controls (fold change = 1.79, p = 0.013 and 2.07, p = 0.030, respectively), RANKL/OPG ratio was significantly decreased (fold change = 0.50, p = 0.020). No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL expression was significantly higher in RA patients with IHD compared to those without IHD (fold change = 1.46, p = 0.033). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased RANKL expression in RA patients (p = 0.016). Our study supports an important role of OPG and TRAIL in RA. Furthermore, it highlights an effect of biologic DMARDs in the modulation of RANKL. PMID- 27403810 TI - Implantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats. AB - The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data. PMID- 27403812 TI - Facile Atmospheric Pressure Synthesis of High Thermal Stability and Narrow-Band Red-Emitting SrLiAl3N4:Eu(2+) Phosphor for High Color Rendering Index White Light Emitting Diodes. AB - Red phosphors (e.g., SrLiAl3N4:Eu(2+)) with high thermal stability and narrow band properties are urgently explored to meet the next-generation high-power white light-emitting diodes (LEDs). However, to date, synthesis of such phosphors remains an arduous task. Herein, we report, for the first time, a facile method to synthesize SrLiAl3N4:Eu(2+) through Sr3N2, Li3N, Al, and EuN under atmospheric pressure. The as-synthesized narrow-band red-emitting phosphor exhibits excellent thermal stability, including small chromaticity shift and low thermal quenching. Intriguingly, the title phosphor shows an anomalous increase in theoretical lumen equivalent with the increase of temperature as a result of blue shift and band broadening of the emission band, which is crucial for high-power white LEDs. Utilizing the title phosphor, commercial YAG:Ce(3+), and InGaN-based blue LED chip, a proof-of-concept warm white LEDs with a color rendering index (CRI) of 91.1 and R9 = 68 is achieved. Therefore, our results highlight that this method, which is based on atmospheric pressure synthesis, may open a new means to explore narrow-band-emitting nitride phosphor. In addition, the underlying requirements to design Eu(2+)-doped narrow-band-emitting phosphors were also summarized. PMID- 27403811 TI - A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing. AB - Site-directed mutagenesis has long been used as a method to interrogate protein structure, function and evolution. Recent advances in massively-parallel sequencing technology have opened up the possibility of assessing the functional or fitness effects of large numbers of mutations simultaneously. Here, we present a protocol for experimentally determining the effects of all possible single amino acid mutations in a protein of interest utilizing high-throughput sequencing technology, using the 263 amino acid antibiotic resistance enzyme TEM 1 beta-lactamase as an example. In this approach, a whole-protein saturation mutagenesis library is constructed by site-directed mutagenic PCR, randomizing each position individually to all possible amino acids. The library is then transformed into bacteria, and selected for the ability to confer resistance to beta-lactam antibiotics. The fitness effect of each mutation is then determined by deep sequencing of the library before and after selection. Importantly, this protocol introduces methods which maximize sequencing read depth and permit the simultaneous selection of the entire mutation library, by mixing adjacent positions into groups of length accommodated by high-throughput sequencing read length and utilizing orthogonal primers to barcode each group. Representative results using this protocol are provided by assessing the fitness effects of all single amino acid mutations in TEM-1 at a clinically relevant dosage of ampicillin. The method should be easily extendable to other proteins for which a high-throughput selection assay is in place. PMID- 27403814 TI - How does wearing a lumbar orthosis interfere with gait initiation? AB - The interaction between medical devices and the human body must be evaluated in standardised laboratory tests. Since wearing a lumbar orthosis is assumed to reduce lower back mobility and reinforce trunk movement control through imposed lordosis, this device is expected to affect gait initiation which requires trunk and pelvic rotations. Thirteen healthy subjects were asked to initiate gait without orthosis (control) and orthosis with or without lordosis constraints. The biomechanical parameters usually reported for gait initiation were studied and no statistically significant effects were found. Indeed, the duration of the anticipation, and execution phases and maximal instantaneous velocity of centre of gravity at the end of the first step were not modified by the experimental conditions. The lack of interference underlines the robustness of the gait initiation parameters, which therefore may lead subjects to adopt adaptive strategies to retain this invariance. Future experiments should be conducted to highlight these strategies. Practitioner Summary: The aim of this study was to investigate the effect of various lumbar orthosis characteristics on gait initiation organisation. The results, based on a dynamic analysis of balance strategies, showed that the medical device had no repercussions on movement control. Several explanations are proposed, which should be validated by future studies. PMID- 27403813 TI - Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel. AB - The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large beta-turn (residues 10-16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02's beta-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel specific blocker complex, which may help guide future drug-design for Kv1.3 related channelopathies. PMID- 27403815 TI - Scanning sports. PMID- 27403816 TI - Coming in sportsmedicine. PMID- 27403817 TI - Sportsmedicine forum. PMID- 27403823 TI - Noteworthy. PMID- 27403822 TI - Running 'Comfortable'. PMID- 27403824 TI - Adherence to Sports-Injury Rehabilitation Programs. AB - In brief: Forty-one injured collegiate athletes completed a rehabilitation adherence questionnaire, addressing the following factors: perceived exertion, pain tolerance, self-motivation, support from significant others, scheduling, and environmental conditions. Multivariate analysis showed a significant difference between the athletes who adhered to their rehabilitation program and those who did not. Those who adhered reported that they (1) were more self-motivated, (2) tolerated pain better, (3) perceived that they worked harder at their rehabilitation, and (4) were less bothered by scheduling of sessions and environmental conditions of athletic training. Based on these findings, the authors suggest ways to enhance rehabilitation adherence. PMID- 27403826 TI - Osteitis Pubis in a Basketball Player. AB - In brief:An 18-year-old male varsity basketball player complained of lower left abdominal pain of a month's duration. Laboratory tests were normal, and no hernia was present. A computed tomography scan showed no abnormality, and fraying of the pubic bone along the symphysis was too subtle to detect on x-ray. A bone scan (pelvic views), however, confirmed a diagnosis of osteitis pubis. Although this disease is self-limited, the patient was treated with corticosteroids and anti inflammatory medication to enhance his comfort. His condition gradually improved within a few months, and he returned to competition the following season. Follow up bone scans at one and two years were normal. PMID- 27403825 TI - Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes. AB - In brief: Monocyte phagocytic function was studied in nine competitive athletes before and after a two-week weight-reduction program of calorie restriction. The phagocytic activity of monocytes before the program was higher in the athletes than in the sedentary controls, but decreased significantly after the weight reduction program. Furthermore, plasma fibronectin concentrations and the response of lymphocytes to phytohemagglutinin decreased after the calorie restriction. These findings suggest that weight reduction by calorie restriction may adversely affect the integrity of defense mechanisms, even in healthy athletes. Thus, calorie restriction in athletes must be conducted with caution to protect them from adverse effects on their physiologic defense mechanisms. PMID- 27403827 TI - Anabolic-Androgenic Steroid Use Among 1,010 College Men. AB - In brief: Little is known about the prevalence of anabolic-androgenic steroid use in the United States. To obtain some initial information, the authors sent questionnaires to male students at three US colleges. Of the 1,010 respondents, 17 (2%) reported using steroids. Most were competitive athletes, but four used steroids primarily to improve personal appearance. Steroid users were not distinguishable from nonusers based on academic achievement or the use of other illicit drugs, cigarettes, or alcohol. The authors point out that the study is exploratory and that the results probably underestimate the true prevalence of steroid use in the United States. PMID- 27403828 TI - A Physiologic Profile Comparing Levels and Styles of Female Dancers. AB - In brief: A physiologic profile comparing 39 female dancers was undertaken to better understand the factors distinguishing four levels and styles of dance: professional ballet (PB), professional modern, university ballet, and university modern. The PB dancers had significantly lower VO2 max values on the tread-mill as well as lower peak blood lactate levels following the Wingate test for anaerobic capacity than the other dancers. The PB dancers also had a significantly higher isokinetic hamstring-quadriceps ratio than the modern dancers. These findings suggest that physiologic capacity may differ among female dancers according to their levels and styles of dance. PMID- 27403829 TI - The Boston Marathon Medical Care Team: Ten Years of Experience. AB - In brief: Over the last decade, an elaborate medical organization has evolved to provide acute care for injured persons at the finish line of the Boston Marathon. The medical team consists of physicians, nurses, podiatrists, physical therapists, athletic trainers, and other nonmedical personnel. The team believes that the most important cause of race injuries is fluid volume depletion; therefore, severely symptomatic athletes are treated early with intravenous fluids. In addition to the medical care team, an ancillary group has been established to maintain medical records, which help to define patterns of injury, thus allowing for more precise planning of medical care. The objective of both groups is not only to improve care at the finish line but also to identify ways to prevent injuries. PMID- 27403830 TI - Injuries in Slow-Pitch Softball. AB - In brief: Softball is one of the most popular recreational sports in the United States, and widespread participation inevitably results in injuries. The authors evaluated the records of 285 patients with softball injuries who were treated at a sports medicine clinic from 1979 through 1986. In addition, they sent questionnaires to 200 registrants in an adult softball league, requesting information about injuries. From this survey, 81 players reported 66 injuries. Many of the injuries were nontraumatic or chronic. The authors suggest ways to prevent softball injuries, such as preseason conditioning and strengthening. PMID- 27403831 TI - Wrist Pain Associated With 'Fractured' Handle Weights in a Tennis Racket. AB - In brief: Three tennis players had vague wrist pain when hitting the ball; all three were using the same racket model. Results of physical examination of the three patients were unremarkable, but x-rays of the tennis rackets showed a 'fracture' in the handle weights. Replacement of the racket with an identical new model relieved the symptoms in all the patients. PMID- 27403832 TI - Study: Breakaway Bases Would Cut Sliding Injuries. AB - Softball players who slide into stationary bases may incur injuries such as sprains and fractures. Researchers say that some of those injuries may be prevented if teams use a base that releases upon contact. PMID- 27403833 TI - The Olympic Training Center: Helping Athletes Improve Their Performance. AB - The Olympic Training Center in Colorado Springs offers a variety of programs to help American athletes optimize their performance. Research in biomechanics and exercise physiology may pay off at the 1988 Summer Games. PMID- 27403834 TI - Boston Marathoners Get Red Carpet Treatment in the Medical Tent. AB - Cool weather prevailed at this year's Boston Marathon, and medical problems were the exception rather than the rule. Nevertheless, the medical team continues searching for ways to improve the care of the runners. PMID- 27403835 TI - Why Do we Sweat? PMID- 27403837 TI - Review of optical breast imaging and spectroscopy. AB - Diffuse optical imaging and spectroscopy of the female breast is an area of active research. We review the present status of this field and discuss the broad range of methodologies and applications. Starting with a brief overview on breast physiology, the remodeling of vasculature and extracellular matrix caused by solid tumors is highlighted that is relevant for contrast in optical imaging. Then, the various instrumental techniques and the related methods of data analysis and image generation are described and compared including multimodality instrumentation, fluorescence mammography, broadband spectroscopy, and diffuse correlation spectroscopy. We review the clinical results on functional properties of malignant and benign breast lesions compared to host tissue and discuss the various methods to improve contrast between healthy and diseased tissue, such as enhanced spectroscopic information, dynamic variations of functional properties, pharmacokinetics of extrinsic contrast agents, including the enhanced permeability and retention effect. We discuss research on monitoring neoadjuvant chemotherapy and on breast cancer risk assessment as potential clinical applications of optical breast imaging and spectroscopy. Moreover, we consider new experimental approaches, such as photoacoustic imaging and long-wavelength tissue spectroscopy. PMID- 27403838 TI - Energy Dispersive X-ray Tomography for 3D Elemental Mapping of Individual Nanoparticles. AB - Energy dispersive X-ray spectroscopy within the scanning transmission electron microscope (STEM) provides accurate elemental analysis with high spatial resolution, and is even capable of providing atomically resolved elemental maps. In this technique, a highly focused electron beam is incident upon a thin sample and the energy of emitted X-rays is measured in order to determine the atomic species of material within the beam path. This elementally sensitive spectroscopy technique can be extended to three dimensional tomographic imaging by acquiring multiple spectrum images with the sample tilted along an axis perpendicular to the electron beam direction. Elemental distributions within single nanoparticles are often important for determining their optical, catalytic and magnetic properties. Techniques such as X-ray tomography and slice and view energy dispersive X-ray mapping in the scanning electron microscope provide elementally sensitive three dimensional imaging but are typically limited to spatial resolutions of > 20 nm. Atom probe tomography provides near atomic resolution but preparing nanoparticle samples for atom probe analysis is often challenging. Thus, elementally sensitive techniques applied within the scanning transmission electron microscope are uniquely placed to study elemental distributions within nanoparticles of dimensions 10-100 nm. Here, energy dispersive X-ray (EDX) spectroscopy within the STEM is applied to investigate the distribution of elements in single AgAu nanoparticles. The surface segregation of both Ag and Au, at different nanoparticle compositions, has been observed. PMID- 27403840 TI - Arsenic Mobilization Is Enhanced by Thermal Transformation of Schwertmannite. AB - Fires in iron-rich seasonal wetlands can thermally transform Fe(III) minerals and alter their crystallinity. However, the fate of As associated with thermally transformed Fe(III) minerals is unclear, as are the consequences for As mobilization during subsequent reflooding and reductive cycles. Here, we subject As(V)-coprecipitated schwertmannite to thermal transformation (200, 400, 600 and 800 degrees C) followed by biotic reductive incubation (150 d) and examine aqueous- and solid-phase speciation of As, Fe and S. Heating to >400 degrees C caused transformation of schwertmannite to a nanocrystalline hematite with greater surface area and smaller particle size. Higher temperatures also caused the initially structurally incorporated As to become progressively more exchangeable, increasing surface-complexed As (AsEx) by up to 60-fold, thereby triggering enhanced As mobilization during incubation (~70-fold in the 800 degrees C treatment). Although more As was mobilized in biotic treatments than controls (~3-20*), in both cases it was directly proportional to initial AsEx and mainly due to abiotic desorption. Higher transformation temperatures also drove divergent pathways of Fe and S biomineralization and led to more As(V) and SO4 reduction relative to Fe(III) reduction. This study reveals thermal transformation of schwertmannite can greatly increase As mobility and has major consequences for As/Fe/S speciation under reducing conditions. Further research is warranted to unravel the wider implications for water quality in natural wetlands. PMID- 27403839 TI - Structural and dynamics studies of a truncated variant of CI repressor from bacteriophage TP901-1. AB - The CI repressor from the temperate bacteriophage TP901-1 consists of two folded domains, an N-terminal helix-turn-helix DNA-binding domain (NTD) and a C-terminal oligomerization domain (CTD), which we here suggest to be further divided into CTD1 and CTD2. Full-length CI is a hexameric protein, whereas a truncated version, CI?58, forms dimers. We identify the dimerization region of CI?58 as CTD1 and determine its secondary structure to be helical both within the context of CI?58 and in isolation. To our knowledge this is the first time that a helical dimerization domain has been found in a phage repressor. We also precisely determine the length of the flexible linker connecting the NTD to the CTD. Using electrophoretic mobility shift assays and native mass spectrometry, we show that CI?58 interacts with the OL operator site as one dimer bound to both half-sites, and with much higher affinity than the isolated NTD domain thus demonstrating cooperativity between the two DNA binding domains. Finally, using small angle X ray scattering data and state-of-the-art ensemble selection techniques, we delineate the conformational space sampled by CI?58 in solution, and we discuss the possible role that the dynamics play in CI-repressor function. PMID- 27403841 TI - Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging. AB - Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure(1). A reliable noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function(2). Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease. PMID- 27403842 TI - Isotropic Growth of Graphene toward Smoothing Stitching. AB - The quality of graphene grown via chemical vapor deposition still has very great disparity with its theoretical property due to the inevitable formation of grain boundaries. The design of single-crystal substrate with an anisotropic twofold symmetry for the unidirectional alignment of graphene seeds would be a promising way for eliminating the grain boundaries at the wafer scale. However, such a delicate process will be easily terminated by the obstruction of defects or impurities. Here we investigated the isotropic growth behavior of graphene single crystals via melting the growth substrate to obtain an amorphous isotropic surface, which will not offer any specific grain orientation induction or preponderant growth rate toward a certain direction in the graphene growth process. The as-obtained graphene grains are isotropically round with mixed edges that exhibit high activity. The orientation of adjacent grains can be easily self adjusted to smoothly match each other over a liquid catalyst with facile atom delocalization due to the low rotation steric hindrance of the isotropic grains, thus achieving the smoothing stitching of the adjacent graphene. Therefore, the adverse effects of grain boundaries will be eliminated and the excellent transport performance of graphene will be more guaranteed. What is more, such an isotropic growth mode can be extended to other types of layered nanomaterials such as hexagonal boron nitride and transition metal chalcogenides for obtaining large-size intrinsic film with low defect. PMID- 27403844 TI - Engineering Bacteria to Catabolize the Carbonaceous Component of Sarin: Teaching E. coli to Eat Isopropanol. AB - We report an engineered strain of Escherichia coli that catabolizes the carbonaceous component of the extremely toxic chemical warfare agent sarin. Enzymatic decomposition of sarin generates isopropanol waste that, with this engineered strain, is then transformed into acetyl-CoA by enzymatic conversion with a key reaction performed by the acetone carboxylase complex (ACX). We engineered the heterologous expression of the ACX complex from Xanthobacter autotrophicus PY2 to match the naturally occurring subunit stoichiometry and purified the recombinant complex from E. coli for biochemical analysis. Incorporating this ACX complex and enzymes from diverse organisms, we introduced an isopropanol degradation pathway in E. coli, optimized induction conditions, and decoupled enzyme expression to probe pathway bottlenecks. Our engineered E. coli consumed 65% of isopropanol compared to no-cell controls and was able to grow on isopropanol as a sole carbon source. In the process, reconstitution of this large ACX complex (370 kDa) in a system naive to its structural and mechanistic requirements allowed us to study this otherwise cryptic enzyme in more detail than would have been possible in the less genetically tractable native Xanthobacter system. PMID- 27403845 TI - Future Papers. PMID- 27403846 TI - Vaginal fluid IL-6 concentrations as a point-of-care test is of value in women with preterm PROM. AB - BACKGROUND: Preterm prelabor rupture of membranes (PROM) is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm PROM is not broadly used in clinical practice, and therefore a shift towards a non-invasive amniotic fluid sampling method is needed. OBJECTIVE: The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intra-amniotic inflammation, and microbial-associated intra-amniotic inflammation in patients with preterm PROM. STUDY DESIGN: A prospective cohort study was conducted in women with singleton gestation complicated by preterm PROM at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive PCR analysis. Intra-amniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration >=745 pg/mL. RESULTS: 1) It was possible to perform the point-of-care assessment of interleukin-6 in vaginal fluid in 92% (141/153) of the women, and only those women were included in the analyses. 2) The rate of microbial invasion of the amniotic cavity and intra-amniotic inflammation was 26% (36/141) and 19% (27/141), respectively. Microbial-associated intra-amniotic inflammation was identified in 12% (17/141) of the women. 3) A strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; p<0.0001). 4) The presence of microbial invasion of the amniotic cavity, intra-amniotic inflammation or microbial associated intra-amniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. 5) A vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity [sensitivity of 53% (19/36), specificity of 89% (93/104), positive predictive value of 63% (19/30), negative predictive value of 85% (93/110), positive likelihood ratio of 5.0 (95% CI 2.5-9.5), and negative likelihood ratio of 0.5 (95% CI 0.4-0.8)], intra-amniotic inflammation [sensitivity of 74% (20/27), specificity of 91% (104/114), positive predictive value of 67% (20/30), negative predictive value of 94% (104/111), positive likelihood ratio of 8.4 (95% CI 4.5 15.9), and negative likelihood ratio of 0.3 (95%CI 0.2-0.5)], and microbial associated intra-amniotic inflammation (sensitivity of 100% (17/17), specificity of 90% (111/124), positive predictive value of 57% (17/30), negative predictive value of 100% (111/111), positive likelihood ratio of 9.5 (95% CI 5.7-16.0), and negative likelihood ratio of 0]. CONCLUSION: The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, non-invasive, and inexpensive method for the identification of intra-amniotic inflammation and microbial associated intra-amniotic inflammation in preterm PROM pregnancies, showing good specificity and negative predictive value. PMID- 27403847 TI - A dynamic quality assessment tool for laparoscopic hysterectomy to measure surgical outcomes. AB - BACKGROUND: The current healthcare system has an urgent need for tools to measure quality. A wide range of quality indicators have been developed in an attempt to differentiate between high-quality and low-quality healthcare processes. However, one of the main issues of currently used indicators is the lack of case-mix correction and improvement possibilities. Case-mix is defined as specific (patient) characteristics that are known to potentially affect (surgical) outcome. If these characteristics are not taken into consideration, comparisons of outcome among healthcare providers may not be valid OBJECTIVE: To develop and test a quality assessment tool for laparoscopic hysterectomy, which can serve as a new outcome quality indicator STUDY DESIGN: This is a prospective international multicenter implementation study. A web-based application (.www.qusum.org) was developed with three main goals: to measure the surgeon's performance using three primary outcomes (blood loss, operative time, and complications); to provide immediate individual feedback using cumulative Observed-minus-Expected graphs; and to detect consistently suboptimal performance after correcting for case-mix characteristics. All gynecologists who perform laparoscopic hysterectomies were requested to register their procedures in the application. A patient safety risk factor checklist was used by the surgeon for reflection. Thereafter, a prospective implementation study was performed, and the application was tested using a survey that included the System Usability Scale. RESULTS: A total of 2066 laparoscopic hysterectomies were registered by 81 gynecologists. Mean operative time was 100+/-39 minutes, blood loss 127+/-163ml, and the complication rate 6.1%. The overall survey response rate was 75%, and the mean System Usability Scale was 76.5+/-13.6, which indicates that the application was good to excellent. The majority of surgeons reported that the application made them more aware of their performance, the outcomes, and patient safety, and they noted that the application provided motivation for improving future performance. CONCLUSIONS: We report the development and test of a real-time, dynamic quality assessment tool for measuring individual surgical outcome for laparoscopic hysterectomy. Importantly, this tool provides opportunities for improving surgical performance. Our study provides a foundation for helping clinicians develop evidence-based quality indicators for other surgical procedures. PMID- 27403848 TI - Detection and successful treatment of emergent anti-SSA mediated fetal atrioventricular block. PMID- 27403849 TI - 'I just don't want to get bullied anymore, then I can lead a normal life'; Insights into life as an obese adolescent and their views on obesity treatment. AB - BACKGROUND: Adolescent obesity is a complex condition involving social, emotional, behavioural and cultural issues. DESIGN: One-to-one interviews and small focus groups with overweight and obese young people were conducted. Qualitative research is an appropriate method to explore the complexity of this issue. SETTING AND PARTICIPANTS: Overweight and obese adolescent's attending a community weight management intervention in South Yorkshire. MAIN VARIABLES STUDIED: Interviews aimed to explore the experiences of obese adolescents and their perspectives towards obesity treatment. RESULTS: Adolescent's provided detailed accounts of their perspectives on weight gain, alluding to disordered patterns of eating and overeating, reported as being triggered by social and emotional factors, and in particular, bullying. Avoidance of bullying and a desire to integrate socially with peers were key drivers to seek treatment. Young people reported what they should do to lose weight, yet responsibility for successful weight loss and lifestyle change was repeatedly attributed to the treatment received, as opposed to viewing this as a combination of self motivation coupled with support provided by friends and family. CONCLUSION: Weight loss programmes need to consider the complex experience of obese young people in their design, focusing on how to implement long-term lifestyle changes. PMID- 27403850 TI - Unsubstituted Benzodithiophene-Based Conjugated Polymers for High-Performance Organic Field-Effect Transistors and Organic Solar Cells. AB - Unsubstituted benzo[1,2-b:4,5-b']dithiophene (BDT) was used to construct a high performance conjugated polymer with 5,6-difluoro-4,7-bis[4-(2 octyldodecyl)thiophene-2-yl]benzo[c][1,2,5] thiadiazole (DTFFBT), named PBDT DTFFBT. The polymer shows the low-lying highest occupied molecular orbital (HOMO) energy level (-5.40 eV) and a broad absorption spectra with strong vibronic absorption peak. Pure polymer films exhibit good crystallinity and edge-on orientation, partially attributed to the BDT units without any side chains, and as a result, the corresponding thin-film transistor showed excellent hole mobility over 1 cm(2) V(-1) s(-1). Interestingly, a well-distributed nanofibrillar polymer aggregation with face-on orientation was obviously formed when blending with PC71BM, which was in favor of the charge transportation. Consequently, the bulk heterojunction polymer solar cells based on the blends showed high power conversion efficiency of 9.29% with large short-current density (14.56 mA cm(-2)) and high fill factor (0.751) without any process additives or thermal annealing. PMID- 27403851 TI - Effects of l-Tyrosine on working memory and inhibitory control are determined by DRD2 genotypes: A randomized controlled trial. AB - l-Tyrosine (TYR), the precursor of dopamine (DA), has been shown to enhance facets of cognitive control in situations with high cognitive demands. However some previous outcomes were mixed: some studies reported significant improvements, while other did not. Given that TYR increases DA level in the brain, we investigated, in a double-blind, randomized, placebo-controlled design, whether the C957T genotypes of a functional synonymous polymorphism in the human dopamine D2 receptor (DRD2) gene (rs6277) contribute to individual differences in the reactivity to TYR administration and whether this factor predicts the magnitude of TYR-induced performance differences on inhibiting behavioral responses in a stop-signal task and working memory (WM) updating in a N-back task. Our findings show that T/T homozygotes (i.e., individuals potentially associated with lower striatal DA level) showed larger beneficial effects of TYR supplementation than C/C homozygotes (i.e., individuals potentially associated with higher striatal DA level), suggesting that genetically determined differences in DA function may explain inter-individual differences in response to TYR supplementation. These findings reinforce the idea that genetic predisposition modulates the effect of TYR in its role as cognitive enhancer. PMID- 27403853 TI - Correction to Electron Flow through Metalloproteins. PMID- 27403852 TI - Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates. AB - Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology. PMID- 27403854 TI - Subject-specific thumb muscle activity during functional tasks of daily life. AB - BACKGROUND: The trapeziometacarpal joint is subjected to high compressive forces during powerful pinch and grasp tasks due to muscle loading. In addition, muscle contraction is important for stability of the joint. The aim of the present study is to explore if different muscle activation patterns can be found between three functional tasks. METHODS: Isometric forces and fine-wire electromyographic (fEMG) activity produced by three intrinsic and four extrinsic thumb muscles were measured in 10 healthy female volunteers. The participants performed isometric contractions in a lateral key pinch, a power grasp and a jar twist task. The tasks were executed with and without EMG recording to verify if electrode placement influenced force production. RESULTS: A subject-specific muscle recruitment was found which remained largely unchanged across tasks. Extrinsic thumb muscles were significantly more active than intrinsic muscles in all tasks. Insertion of the fEMG electrodes decreased force production significantly in all tasks. CONCLUSION: The thumb muscles display a high variability in muscle activity during functional tasks of daily life. The results of this study suggest that to produce a substantial amount of force, a well-integrated, but subject specific, co-contraction between the intrinsic and extrinsic thumb muscles is necessary. PMID- 27403855 TI - How reliable are lower limb biomechanical variables during running and cutting tasks. AB - The purpose of this study was to compare the within- and between-days reliability of lower limb biomechanical variables collected during running and cutting tasks. METHODS: 15 recreational athletes, 7 males and 8 females, took part in three testing sessions, two sessions on the same day with an hour gap and another session one week later. Kinematic and kinetic data during running and 90 degrees side step cutting tasks gathered using a ten-camera motion analysis system (Qualisys) and a force platform (AMTI) embedded into the floor. RESULTS: During both tasks, within-day ICC values for joint angles (ICCrun=0.63-0.94 and ICCcut=0.63-0.96) were higher than between days (ICCrun=0.51-0.72 and ICCcut=0.42 0.83). Out of five moments tested in each task, within-day ICC values (ICCrun=0.64-0.89 and ICCcut=0.79-0.94) were higher than between days (ICCrun=0.58-0.91 and ICCcut=0.83-0.92). During running task, within and between day SEM values for joint moments ranged between (0.07-0.39Nmkg) and between (0.98 degrees -5.14 degrees ) for joint angles. While during cutting, SEM values for moments ranged between (0.13-0.56Nmkg) and between (1.73-5.15) for joint angle measurement. The GRF data, in both tasks, were more reliable (ICCrun?0.84 and ICCcut?0.88) as compared to angles (ICCrun?0.51 and ICCcut?0.42), and moments (ICCrun?0.58 and ICCcut?0.79) data. These findings are relevant to those undertaking intervention studies because of the potential for large measurement variability when examining certain variables, which would then require considerable changes in these variables to show "real" effects of the interventions beyond measurement error. PMID- 27403856 TI - Glucose Promotes a Pro-Oxidant and Pro-Inflammatory Stromal Microenvironment Which Favors Motile Properties in Breast Tumor Cells. AB - Chronic inflammation and metabolic reprogramming have been proposed as hallmarks of cancer development. Currently, many of the functional clues between these two phenomena are studied under the integrative view of functional stroma-epithelia interaction. It has been proposed that stromal cells, due to their abundance and avidity for glucose, are able to modify the metabolic behavior of an entire solid tumor. In the present study, using a mammary stromal cell line derived from healthy tissue subjected to long-term culture in low (5 mM) or high (25 mM) glucose, we found that the hyperglycemic condition favors the establishment of a pro-inflammatory and pro-oxidant environment characterized by the induction of the COX-2/PGE2 axis. In this condition, epithelial migration was stimulated. Moreover, we also found that stromal-derived PGE2, acting as a stimulator of IL-1 epithelial expression was one of the factors that promote the acquisition of motile properties by epithelial cells and the maintenance of a COX-2/PGE2 dependent inflammatory condition. Overall, our work provides experimental evidence that glucose stimulates a tumor inflammatory environment that, as a result of a functional cross-talk between stroma and epithelia, may be responsible for tumor progression. J. Cell. Biochem. 118: 994-1002, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27403857 TI - Effect of Cryopreservation and Post-Cryopreservation Somatic Embryogenesis on the Epigenetic Fidelity of Cocoa (Theobroma cacao L.). AB - While cocoa plants regenerated from cryopreserved somatic embryos can demonstrate high levels of phenotypic variability, little is known about the sources of the observed variability. Previous studies have shown that the encapsulation dehydration cryopreservation methodology imposes no significant extra mutational load since embryos carrying high levels of genetic variability are selected against during protracted culture. Also, the use of secondary rather than primary somatic embryos has been shown to further reduce the incidence of genetic somaclonal variation. Here, the effect of in vitro conservation, cryopreservation and post-cryopreservation generation of somatic embryos on the appearance of epigenetic somaclonal variation were comparatively assessed. To achieve this we compared the epigenetic profiles, generated using Methylation Sensitive Amplified Polymorphisms, of leaves collected from the ortet tree and from cocoa somatic embryos derived from three in vitro conditions: somatic embryos, somatic embryos cryopreserved in liquid nitrogen and somatic embryos generated from cryoproserved somatic embryos. Somatic embryos accumulated epigenetic changes but these were less extensive than in those regenerated after storage in LN. Furthermore, the passage of cryopreserved embryos through another embryogenic stage led to further increase in variation. Interestingly, this detected variability appears to be in some measure reversible. The outcome of this study indicates that the cryopreservation induced phenotypic variability could be, at least partially, due to DNA methylation changes. KEY MESSAGE: Phenotypic variability observed in cryostored cocoa somatic-embryos is epigenetic in nature. This variability is partially reversible, not stochastic in nature but a directed response to the in vitro culture and cryopreservation. PMID- 27403858 TI - Techno-economic analysis of different pretreatment processes for lignocellulosic based bioethanol production. AB - In this work, a method based on process synthesis, simulation and evaluation has been used to setup and study the industrial scale lignocellulosic bioethanol productions processes. Scenarios for pretreatment processes of diluted acid, liquid hot water and ammonia fiber explosion were studied. Pretreatment reactor temperature, catalyst loading and water content as well as solids loading in the hydrolysis reactor were evaluated regarding its effects on the process energy consumption and bioethanol concentration. The best scenarios for maximizing ethanol concentration and minimizing total annual costs (TAC) were selected and their minimum ethanol selling price was calculated. Ethanol concentration in the range of 2-8% (wt.) was investigated after the pretreatment. The best scenarios maximizing the ethanol concentration and minimizing TAC obtained a reduction of 19.6% and 30.2% respectively in the final ethanol selling price with respect to the initial base case. PMID- 27403859 TI - Culture modes and financial evaluation of two oleaginous microalgae for biodiesel production in desert area with open raceway pond. AB - Cultivation modes of autotrophic microalgae for biodiesel production utilizing open raceway pond were analyzed in this study. Five before screened good microalgae were tested their lipid productivity and biodiesel quality again in outdoor 1000L ORP. Then, Chlorella sp. L1 and Monoraphidium dybowskii Y2 were selected due to their stronger environmental adaptability, higher lipid productivity and better biodiesel properties. Further scale up cultivation for two species with batch and semi-continuous culture was conducted. In 40,000L ORP, higher lipid productivity (5.15 versus 4.06gm(-2)d(-1) for Chlorella sp. L1, 5.35 versus 3.00gm(-2)d(-1) for M. dybowskii Y2) was achieved in semi-continuous mode. Moreover, the financial costs of 14.18$gal(-1) and 13.31$gal(-1) for crude biodiesel in two microalgae with semi-continuous mode were more economically feasible for commercial production on large scale outdoors. PMID- 27403860 TI - Partial nitrification and denitrification of mature landfill leachate using a pilot-scale continuous activated sludge process at low dissolved oxygen. AB - Controlling of low dissolved oxygen (DO) levels (0.1-0.5mg/L), a cost-effective strategy, was applied to a pilot-scale anoxic-oxic-oxic-anoxic process for partial nitrification and denitrification of mature landfill leachate. High ammonium removal efficiency, stable nitrite accumulation rate and total nitrogen removal efficiency was higher than 95.0%, 90.0% and 66.4%, respectively, implying potential application of this process for nitrogen removal of mature landfill leachate. Efficient nitrite accumulation in the first oxic reactor depended on low DO conditions and sufficient alkalinity. However, operational limit was mainly decided by actual hydraulic retention time (AHRT) of the first oxic reactor and appeared with AHRT less than 13.9h under DO of 0.3-0.5mg/L. High throughput sequencing analysis demonstrated significant change of bacterial diversity in the first oxic reactor after a long-term operation and dominant bacteria genus Nitrosomonas was shown to be responsible for NH4(+)-N removal and nitrite accumulation under low DO levels. PMID- 27403861 TI - Sugarcane vinasse CO2 gasification and release of ash-forming matters in CO2 and N2 atmospheres. AB - Gasification of sugarcane vinasse in CO2 and the release of ash-forming matters in CO2 and N2 atmospheres were investigated using a differential scanning calorimetry and thermogravimetric analyzer (DSC-TGA) at temperatures between 600 and 800 degrees C. The results showed that pyrolysis is the main mechanism for the release of the organics from vinasse. Release of ash-forming matters in the vinasse is the main cause for vinasse char weight losses in the TGA above 700 degrees C. The losses are higher in N2 than in CO2, and increase considerably with temperature. CO2 gasification also consumes the carbon in the vinasse chars while suppressing alkali release. Alkali release was also significant due to volatilization of KCl and reduction of alkali sulfate and carbonate by carbon. The DSC measured thermal events during heating up in N2 atmosphere that correspond to predicted melting temperatures of alkali salts in the char. PMID- 27403862 TI - Problems With Large Joints: Foreword. PMID- 27403863 TI - Problems With Large Joints: Knee Conditions. AB - As a large joint dependent on ligaments for stability and muscles and tendons for function, the knee is susceptible to a spectrum of acute and overuse injuries. Acute injuries involve the ligaments, menisci, and weight-bearing surfaces. Overuse injuries commonly affect the patellar tendon, iliotibial band, and patellofemoral complex. Acute and overuse knee injuries can be debilitating but most can be diagnosed and managed by family physicians. An appropriate history and physical examination are essential to guide diagnosis and management decisions. X-ray imaging often is required. Magnetic resonance imaging study, computed tomography scan, or ultrasonography also may be indicated to guide diagnosis and management. Knee injuries often improve with bracing, activity modification, weight loss, and physical therapy. Referral to an orthopedic subspecialist can be considered when these measures are not effective. PMID- 27403864 TI - Problems With Large Joints: Hip Conditions. AB - Common overuse injuries of the hip include greater trochanteric pain syndrome (GTPS) and coxa saltans (ie, snapping hip). GTPS, previously called trochanteric bursitis, is a regional chronic pain syndrome. Etiologies include gluteal tendinitis or tendinosis, gluteal muscle or tendon tears, bursitis, meralgia paresthetica, iliotibial band disorders, and referred osteoarthritis pain. Treatment typically consists of activity modification and physical therapy (PT). Snapping hip can have multiple etiologies. Extra-articular etiologies include iliotibial band syndrome and iliopsoas snapping. Patients typically are treated with activity modification and PT. Intra-articular snapping usually is the result of chondral or acetabular labral injuries, and may require surgical intervention. Femoroacetabular impingement is an emerging etiology of hip pain. Patients commonly report anterior hip or groin pain with insidious onset. It results from cam-type impingement from an irregular shape of the femoral head-neck junction, pincer-type impingement from the acetabulum, or mixed-type impingement resulting from a combination of abnormalities. This atypical morphology can lead to labral tears or chondral injuries, which may manifest as painful clicking or popping. Treatments range from conservative, including activity modification, anti inflammatory drugs, and PT, to surgical correction of the atypical morphology and addressing labral or chondral damage when present. PMID- 27403865 TI - Problems With Large Joints: Shoulder Conditions. AB - The shoulder is the most mobile joint in the body. It requires an extensive support system to create mobility while providing stability. Although there are many etiologies of shoulder pain, weakness, and instability, most injuries in the shoulder are due to overuse. Rotator cuff tears, labral tears, calcific tendinopathy, and impingement often result from chronic overuse injuries. Acute injuries include dislocations that can cause labral tears or other complications. Frozen shoulder refers to a typically benign condition of restricted range of motion that may spontaneously resolve but can cause prolonged pain and discomfort. The history combined with specific shoulder examination techniques can help family physicians successfully diagnose shoulder conditions. X-ray imaging typically is sufficient to rule out more serious etiologies when evaluating patients with shoulder conditions. However, imaging with magnetic resonance imaging (MRI) study or ultrasonography for rotator cuff tears, and MRI study with intra-articular contrast for labral tears, is needed to confirm these diagnoses. Corticosteroid injections and physical therapy are first-line treatments for most shoulder conditions. Surgical options typically are reserved for patients for whom conservative treatments are ineffective, and typically are performed arthroscopically. PMID- 27403866 TI - Problems With Large Joints: Rehabilitation. AB - Patients with musculoskeletal injuries to large joints often improve with physical rehabilitation. Injuries typically result from acute macrotrauma or chronic repetitive microtraumatic overuse. Rehabilitation may require therapeutic exercise techniques to regain range of motion and flexibility, increase local muscular strength and endurance, decrease swelling, and reduce pain. Rehabilitation specialists may use additional modalities, such as heat or ultrasound, to decrease acute pain or swelling, although evidence for these modalities is mixed. In addition to treatment for acute or chronic injury, rehabilitation can prevent musculoskeletal injury or deterioration in chronic conditions such as arthritis. A trial of rehabilitation is appropriate in many patients with neuromusculoskeletal conditions to address loss of physical function due to pain, immobility, decreased flexibility, decreased muscular strength and endurance, joint instability, or loss of balance. PMID- 27403867 TI - Associations between Recreational and Commuter Cycling, Changes in Cycling, and Type 2 Diabetes Risk: A Cohort Study of Danish Men and Women. AB - BACKGROUND: Cycling is a recreational activity and mode of commuting with substantial potential to improve public health in many countries around the world. The aim of this study was to examine prospective associations between recreational and commuter cycling, changes in cycling habits, and risk of type 2 diabetes (T2D) in Danish adults from the Diet, Cancer and Health cohort study. METHODS AND FINDINGS: At baseline from 1993 to 1997, 24,623 men and 27,890 women from Denmark, 50-65 y of age and free of T2D and other chronic diseases, underwent a number of assessments, including completing a lifestyle questionnaire also addressing cycling habits. Approximately 5 y later, at a second examination, participants completed a new, updated lifestyle questionnaire. Cox regression was used to estimate hazard ratios (HRs) of incident T2D registered in the Danish National Diabetes Registry, according to recreational and commuter cycling and changes in cycling habits, with adjustment for a priori known T2D risk factors. During 743,245.4 person-years of follow-up (mean follow-up 14.2 y), 6,779 incident cases of T2D were documented. Multivariable adjusted HRs (95% confidence interval [CI]) were 1, 0.87 (0.82, 0.93), 0.83 (0.77, 0.89), 0.80 (0.74, 0.86) and 0.80 (0.74, 0.87) (p for trend = <0.001) for 0, 1-60, 61-150, 151-300, and >300 min/wk of total cycling (recreational and commuter cycling), respectively. In analysis of seasonal cycling, multivariable adjusted HRs (95% CI) were 1, 0.88 (0.83, 0.94), and 0.80 (0.76, 0.85) for non-cyclists, seasonal cyclists (those cycling only in summer or winter), and those cycling during both summer and winter, respectively. How changes in total cycling from baseline to the second examination affected risk was also investigated, and multivariable adjusted HRs (95% CI) were 1, 0.88 (0.78, 1.01), 0.80 (0.69, 0.91), and 0.71 (0.65, 0.77) for non-cyclists and for those who ceased, initiated, or continued cycling between baseline and the second examination, respectively. Lastly, in the analysis of commuter cycling, multivariable HRs (95% CI) were 1, 0.72 (0.60, 0.87), 0.83 (0.69, 1.00), and 0.70 (0.57, 0.85) (p for trend = <0.001) for cycling 0, 1-60, 61-150, and >150 min/wk to work, respectively. The main limitation of the current study is the use of self-reported physical activity. CONCLUSIONS: Commuter and recreational cycling was consistently associated with lower risk of T2D in Danish adults. Our results also provide evidence that late-in-life initiation of or continued engagement in cycling lowers risk of T2D. PMID- 27403869 TI - Reduced alpha-gamma phase amplitude coupling over right parietal cortex is associated with implicit visuomotor sequence learning. AB - Implicit visuomotor sequence learning is important for our daily life, e.g., when writing or playing an instrument. Previous research identified a network of cortical regions that is relevant for motor sequence learning, namely primary motor cortex, premotor cortex, superior parietal cortex, and subcortical regions, including basal ganglia and cerebellum. Here, we investigated learning-related changes in oscillatory activity (theta, alpha and gamma power) and cross frequency interactions (theta- and alpha-gamma phase-amplitude coupling) within cortical regions during sensorimotor memory formation. EEG was recorded from a large group of participants (n=73) performing the serial reaction time task (SRTT). Posterior parietal alpha power was larger early-on during sequence learning and smaller in later sessions. Alpha/low-gamma (8-13Hz and 30-48Hz) phase-amplitude coupling (PAC) was significantly smaller during sequence learning over right superior parietal cortex and frontal cortex. During the transition from sequential stimuli to random stimuli, participants made more errors, indicating that they still implicitly attempted to implement the learned motor sequence. At the same time, alpha/low-gamma phase-amplitude coupling was found to be smaller during the transition relative to later random trials. Our results show that learning and implementing a learned motor sequence reduces alpha/low gamma PAC over parietal and frontal cortex. Fronto-parietal alpha/low-gamma PAC might be relevant for visuomotor mapping which becomes less relevant once the motor sequence has been encoded. PMID- 27403870 TI - Communities stimulated with ethanol to perform direct interspecies electron transfer for syntrophic metabolism of propionate and butyrate. AB - Direct interspecies electron transfer (DIET) has been considered as an alternative to interspecies H2 transfer (IHT) for syntrophic metabolism, but the microorganisms capable of metabolizing the key intermediates, such as propionate and butyrate, via DIET have yet to be described. A strategy of culturing the enrichments with ethanol as a DIET substrate to stimulate the communities for the syntrophic metabolism of propionate and/or butyrate was proposed in this study. The results showed that the syntrophic propionate and/or butyrate degradation was significantly improved in the ethanol-stimulated reactor when propionate/butyrate was the sole carbon source. The conductivity of the ethanol-stimulated enrichments was as 5 folds (for propionate)/76 folds (for butyrate) as that of the traditional enrichments (never ethanol fed). Microbial community analysis revealed that Geobacter species known to proceed DIET were only detected in the ethanol-stimulated enrichments. Together with the significant increase of Methanosaeta and Methanosarcina species in these enrichments, the potential DIET between Geobacter and Methanosaeta or Methanosarcina species might be established to improve the syntrophic propionate and/or butyrate degradation. Further experiments demonstrated that granular activated carbon (GAC) could improve the syntrophic metabolism of propionate and/or butyrate of the ethanol-stimulated enrichments, while almost no effects on the traditional enrichments. Also, the high H2 partial pressure could inhibit the syntrophic propionate and/or butyrate degradation of the traditional enrichments, but its effect on that of the ethanol stimulated enrichments was negligible. PMID- 27403868 TI - Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies. AB - Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions. PMID- 27403871 TI - Transparent exopolymer particles (TEP) removal efficiency by a combination of coagulation and ultrafiltration to minimize SWRO membrane fouling. AB - This study investigated the impact of coagulation on the transformation between colloidal and particulate transparent exopolymer particles (TEP) in seawater; and the effectiveness of a combined pretreatment consisting of coagulation and UF on minimizing TEP fouling of seawater reverse osmosis (SWRO) membranes. Coagulation with ferric chloride at pH 5 substantially transformed colloidal TEP (0.1-0.4) into particulate TEP (>0.4) leading to a better membrane fouling control. Both 50 and 100 kDa molecular weight cut-off (MWCO) UF membranes removed most of particulate and colloidal TEP without the assistance of coagulation, but coagulation is still necessary for better UF fouling control. The improvement of combined SWRO pretreatment with coagulation and 50 kDa UF membranes was not that much significant compared to UF pretreatment with 50 KDa alone. Therefore, the minimal coagulant dosage for seawater containing TEP should be based on the UF fouling control requirements rather than removal efficiency. PMID- 27403872 TI - Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. AB - Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent and-sludge separation and AS recycling. However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. PMID- 27403873 TI - Micropollutant degradation, bacterial inactivation and regrowth risk in wastewater effluents: Influence of the secondary (pre)treatment on the efficiency of Advanced Oxidation Processes. AB - In this work, disinfection by 5 Advanced Oxidation Processes was preceded by 3 different secondary treatment systems present in the wastewater treatment plant of Vidy, Lausanne (Switzerland). 5 AOPs after two biological treatment methods (conventional activated sludge and moving bed bioreactor) and a physiochemical process (coagulation-flocculation) were tested in laboratory scale. The dependence among AOPs efficiency and secondary (pre)treatment was estimated by following the bacterial concentration i) before secondary treatment, ii) after the different secondary treatment methods and iii) after the various AOPs. Disinfection and post-treatment bacterial regrowth were the evaluation indicators. The order of efficiency was Moving Bed Bioreactor > Activated Sludge > Coagulation-Flocculation > Primary Treatment. As far as the different AOPs are concerned, the disinfection kinetics were: UVC/H2O2 > UVC and solar photo-Fenton > Fenton or solar light. The contextualization and parallel study of microorganisms with the micropollutants of the effluents revealed that higher exposure times were necessary for complete degradation compared to microorganisms for the UV-based processes and inversed for the Fenton-related ones. Nevertheless, in the Fenton-related systems, the nominal 80% removal of micropollutants deriving from the Swiss legislation, often took place before the elimination of bacterial regrowth risk. PMID- 27403874 TI - Superiority of wet-milled over dry-milled superfine powdered activated carbon for adsorptive 2-methylisoborneol removal. AB - Superfine powdered activated carbon (SPAC), which is produced from conventionally sized powdered activated carbon (PAC) by wet milling in a bead mill, has attracted attention for its high adsorptive removal ability in both research and practice. In this study, the performance of dry-milled SPAC was investigated. 2 Methylisoborneol (MIB), an earthy-musty compound commonly targeted by water treatment systems, was used as the target adsorbate. Dry-milled SPAC exhibited lower adsorptive removal of MIB than wet-milled SPAC, even when both SPACs were produced from the same PAC and were composed of particles of the same size. One reason for the lower removal of MIB by the dry-milled SPAC was a higher degree of aggregation in the dry-milled SPAC after production; as a result the apparent particle size of dry-milled SPAC was larger than that of wet-milled SPAC. The dry milled SPAC was also more negatively charged than the wet-milled SPAC, and, owing to its higher repulsion, it was more amenable to dispersion by ultrasonication. However, even after the dry-milled SPAC was ultrasonicated so that its apparent particle size was similar to or less than that of the wet-milled SPAC, the dry milled SPAC was still inferior in adsorptive removal to the wet-milled SPAC. Therefore, another reason for the lower adsorptive removal of dry-milled SPAC was its lower equilibrium adsorption capacity due to the oxidation during the milling. The adsorption kinetics by SPACs with different degrees of particle aggregation were successfully simulated by a pore diffusion model and a fractal aggregation model. PMID- 27403875 TI - Iron-Catalyzed Reaction of Urea with Alcohols and Amines: A Safe Alternative for the Synthesis of Primary Carbamates. AB - A general study of the iron-catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamate), without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono- and disubstituted ureas via selective transamidation reaction. These atom-economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis-acidic iron(II) catalyst. PMID- 27403876 TI - Arginine and Caries Prevention: A Systematic Review. AB - OBJECTIVES: To evaluate the available evidence that the use of arginine containing dental care products prevents the development of new caries lesions and the progression of existing lesions. SEARCH METHODS: We performed a systematic literature search of databases including PubMed, the Cochrane Library and EMBASE. SELECTION CRITERIA: We selected randomized controlled trials of treatment with arginine in fluoride-containing dental products measuring dental caries incidence or progression in children, adults and elderly subjects. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for risk of bias and evaluated overall study quality using the GRADE classification. MAIN RESULTS: Due to conflicts of interest and weak transferability to Swedish conditions, no conclusions can be drawn from studies on the effects of arginine fluoride toothpaste in children. Arginine-containing toothpaste costs about 40% more than basic fluoride toothpaste; to determine whether it is more cost effective, the higher cost must be considered in relation to any additional caries-preventive effect. The literature review also disclosed some questionable research ethics: in several of the studies, the children in the control group used non-fluoride toothpaste. Toothpaste without fluoride is not as effective against dental caries as the standard treatment - fluoride toothpaste - which has a well-documented effect. This contravenes the fundamental principles of research ethics. CONCLUSION: At present there is insufficient evidence in support of a caries-preventive effect for the inclusion of arginine in toothpastes. More rigorous studies, and studies which are less dependent on commercial interests, are required. PMID- 27403877 TI - Correlates of Intra-Household ITN Use in Liberia: A Multilevel Analysis of Household Survey Data. AB - Malaria is a major cause of morbidity and mortality in Liberia. At the same time, insecticide-treated net (ITN) ownership and use remain low. Access is a key determinant of ITN use but it is not the only one; prior studies have identified factors that affect the use of ITNs in households with at least one ITN. These factors operate at the individual, household, and community levels. However, studies have generally not assessed the psychosocial or ideational determinants of ITN use. Using 2014 household survey data, this manuscript examines the socio demographic, ideational, household, and community factors associated with household member use of ITNs in Liberia. Multilevel modeling was used to assess fixed effects at the individual, household, and community levels, and random effects at the household and cluster levels. The data showed significant residual clustering at the household level, indicating that there were unmeasured factors operating at this level that are associated with ITN use. The association of age with ITN use was moderated by sex such that men, older children, and teenagers were less likely to sleep under an ITN compared to women and children under five years old. Female caregivers' perceived severity of malaria, perceived self efficacy to detect a complicated case of malaria, and exposure to the "Take Cover" communication campaign were positively associated with ITN use by members of her household. The association with household size was negative, while the relationship with the number of ITNs was positive. Programs should seek to achieve universal coverage (that is, one ITN for every two household members) and promote the notion that everyone needs to sleep under an ITN every night. Programs should also seek to strengthen perceived severity of malaria and educate intended audience groups on the signs of malaria complications. Given the significance of residual clustering at the household level, interventions that engage men as heads of household and key decision-makers are relevant. PMID- 27403878 TI - Is There a Difference in Stability After Intraoral Vertical Ramus Osteotomy Between Vertically High-Angle and Normal-Angle Patients? AB - PURPOSE: Few studies have evaluated the relapse pattern of intraoral vertical ramus osteotomy (IVRO) for the correction of mandibular prognathism with a high angle. The aim of this study was to measure the association between vertical facial types (high and normal mandibular plane angle) and relapse after IVRO for the management of mandibular prognathism. MATERIALS AND METHODS: The retrospective cohort study sample (skeletal Class III patients) was divided into 2 groups according to the angle of the sella-nasion plane relative to the mandibular plane (SN-MP) at the initial examination. Lateral cephalograms were analyzed for the predictor (facial type) and outcome (cephalometric changes over time) variables before surgery, 7 days after surgery, and 12 months after surgery. The 2 groups were matched for sample size (n = 20 in each). Data were analyzed using repeated-measures analysis of variance with Bonferroni correction. RESULTS: The normal-angle group (group N, SN-MP from 27 degrees to 37 degrees ) and high-angle group (group H, SN-MP >37 degrees ) were not significantly different in terms of gender and age at the initial examination. Seven days after surgery, the mandibles in group H moved 2.5 mm more superiorly than those in group N (P = .013); consequently, the amount of overbite correction in group H was approximately 2 mm greater than that in group N (P = .002). Nevertheless, 12 months after surgery, there was no statistically significant difference in relapse of the maxilla and mandible between the 2 groups. In the 2 groups, the mandible moved approximately 0.7 mm superiorly during retention. CONCLUSIONS: These findings suggest that IVRO is a clinically acceptable and stable treatment modality for mandibular prognathism with a high angle. PMID- 27403881 TI - Cellulose as a Scaffold for Self-Assembly: From Basic Research to Real Applications. AB - Cellulose has received a tremendous amount of attention both in academia and industry owing to its unique structural features, impressive physical-chemical properties, and wide applications. This natural polymer is originally used for packaging, paper, lightweight composites, and so forth and is now being developed for various new areas, such as antibacterial treatment, catalysis, water purification and separation, and biological and environmental analysis. In the current article, we summarize the recent developments in the self-assembly of cellulose with various species including metal ions and metal and metal oxide nanoparticles. Then we highlight several key application areas of cellulose-based composites by reviewing the recent representative literature in each area. A significant part of this review demonstrates some exciting innovations for a wide range of practical applications of cellulose-based composites. Some challenges are also discussed with a view toward future developments. PMID- 27403880 TI - A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-beta accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload. AB - Iron-overload can cause cognitive impairment due to blood-brain barrier (BBB) breakdown and brain mitochondrial dysfunction. Although deferiprone (DFP) has been shown to exert neuroprotection, the head-to-head comparison among iron chelators used clinically on brain iron-overload has not been investigated. Moreover, since antioxidant has been shown to be beneficial in iron-overload condition, its combined effect with iron chelator has not been tested. Therefore, the hypothesis is that all chelators provide neuroprotection under iron-overload condition, and that a combination of an iron chelator with an antioxidant has greater efficacy than monotherapy. Male Wistar rats (n=42) were assigned to receive a normal diet (ND) or a high-iron diet (HFe) for 4months. At the 2nd month, HFe-fed rats were treated with a vehicle, deferoxamine (DFO), DFP, deferasirox (DFX), n-acetyl cysteine (NAC) or a combination of DFP with NAC, while ND-fed rats received vehicle. At the end of the experiment, rats were decapitated and brains were removed to determine brain iron level and deposition, brain mitochondrial function, BBB protein expression, brain mitochondrial dynamic, brain apoptosis, tau-hyperphosphorylation, amyloid-beta (Abeta) accumulation and dendritic spine density. The results showed that iron-overload induced BBB breakdown, brain iron accumulation, brain mitochondrial dysfunction, impaired brain mitochondrial dynamics, tau-hyperphosphorylation, Abeta accumulation and dendritic spine reduction. All treatments, except DFX, attenuated these impairments. Moreover, combined therapy provided a greater efficacy than monotherapy. These findings suggested that iron-overload induced brain iron toxicity and a combination of an iron chelator with an antioxidant provided a greatest efficacy for neuroprotection than monotherapy. PMID- 27403879 TI - Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus. AB - In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus (CN). However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and CN neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination. PMID- 27403882 TI - Estimation of the Undiagnosed Intervals of HIV-Infected Individuals by a Modified Back-Calculation Method for Reconstructing the Epidemic Curves. AB - BACKGROUND: Undiagnosed infections accounted for the hidden proportion of HIV cases that have escaped from public health surveillance. To assess the population risk of HIV transmission, we estimated the undiagnosed interval of each known infection for constructing the HIV incidence curves. METHODS: We used modified back-calculation methods to estimate the seroconversion year for each diagnosed patient attending any one of the 3 HIV specialist clinics in Hong Kong. Three approaches were used, depending on the adequacy of CD4 data: (A) estimating one's pre-treatment CD4 depletion rate in multilevel model;(B) projecting one's seroconversion year by referencing seroconverters' CD4 depletion rate; or (C) projecting from the distribution of estimated undiagnosed intervals in (B). Factors associated with long undiagnosed interval (>2 years) were examined in univariate analyses. Epidemic curves constructed from estimated seroconversion data were evaluated by modes of transmission. RESULTS: Between 1991 and 2010, a total of 3695 adult HIV patients were diagnosed. The undiagnosed intervals were derived from method (A) (28%), (B) (61%) and (C) (11%) respectively. The intervals ranged from 0 to 10 years, and were shortened from 2001. Heterosexual infection, female, Chinese and age >64 at diagnosis were associated with long undiagnosed interval. Overall, the peaks of the new incidence curves were reached 4-6 years ahead of reported diagnoses, while their contours varied by mode of transmission. Characteristically, the epidemic growth of heterosexual male and female declined after 1998 with slight rebound in 2004-2006, but that of MSM continued to rise after 1998. CONCLUSIONS: By determining the time of seroconversion, HIV epidemic curves could be reconstructed from clinical data to better illustrate the trends of new infections. With the increasing coverage of antiretroviral therapy, the undiagnosed interval can add to the measures for assessing HIV transmission risk in the population. PMID- 27403883 TI - Signaling pathways involved in cardiac energy metabolism. AB - Various signaling pathways coordinate energy metabolism and contractile function in the heart. Myocardial uptake of long-chain fatty acids largely occurs by facilitated diffusion, involving the membrane-associated protein, CD36. Glucose uptake, the rate-limiting step in glucose utilization, is mediated predominantly by the glucose transporter protein, GLUT4. Insulin and contraction-mediated AMPK signaling each are implicated in tightly regulating these myocardial 'gate keepers' of energy balance, that is, CD36 and GLUT4. The insulin and AMPK signaling cascades are complex and their cross-talk is only beginning to be understood. Moreover, transcriptional regulation of the CD36 and GLUT4 is significantly understudied. This review focuses on recent advances on the role of these signaling pathways and transcription factors involved in the regulation of CD36 and GLUT4. PMID- 27403884 TI - Compositional tuning of epoxide-polyetheramine "click" reaction toward cytocompatible, cationic hydrogel particles with antimicrobial and DNA binding activities. AB - The "click" characteristics of nucleophilic opening of epoxide have recently been exploited for the development of a functional hydrogel particle system based on commercially available bisepoxide and triamine polyetheramine monomers. Key features of these particles include high cationic charges and responsiveness to temperature, pH, and oxidation. Despite these advantages, the cytocompatibility of these particles must be considered prior to use in biomedical applications. Here we demonstrate that, by introducing a diamine polyetheramine as a comonomer in the "click" reaction, and tuning its molar ratio with the triamine monomer, cationic nanoparticles with improved cytocompatibility can be prepared. The reduced cytotoxicity is primarily due to the hydrophilic backbone of the diamine comonomer, which has polyethylene glycol as a primary component. The resulting nanoparticles formed from the diamine comonomer exhibited a lower surface charge, while maintaining a comparable size. In addition, the responsiveness of the nanoparticles to temperature, pH, and oxidation was conserved, while achieving greater colloidal stability at basic pH. Results from this study further demonstrated that the nanoparticles were able to encapsulate Nile red, a model for hydrophobic drug molecules, were effective against the bacteria Staphylococcus aureus, and were capable of binding DNA through ionic complexation. Based on the results from this work, the use of diamine comonomers significantly reduces the cytotoxicity of similarly developed hydrogel nanoparticles, allowing for numerous biomedical applications, including nanocarriers for therapeutic agents with poor water solubility, treatment of bacterial infection, and non-viral vectors for gene therapy. STATEMENT OF SIGNIFICANCE: In recent years significant attention has been placed on the development of nanocarriers for numerous biomedical applications. Of particular interest are cationic polymers, which contain high positive surface charges that allow binding of numerous therapeutic agents. Unfortunately, the advantages of cationic polymers for binding, are often negated by the tendency of these polymers to be cytotoxic. Previous studies have developed highly responsive cationic hydrogel nanoparticles, which meet several of the criteria for biomedical applications, but were acutely cytotoxic. In this work, cationic hydrogel nanoparticles, with significantly improved cytocompatibility, were synthesized using simple, green epoxy chemistry. In addition, the ability of these nanoparticles to maintain a small size (<500nm), bind DNA, encapsulate hydrophobic drugs, and kill bacteria was maintained. PMID- 27403885 TI - Mechanics of soft epithelial keratin networks depend on modular filament assembly kinetics. AB - Structural adaptability is a pivotal requirement of cytoskeletal structures, enabling their reorganization to meet the cellular needs. Shear stress, for instance, results in large morphological network changes of the human soft epithelial keratin pair K8:K18, and is accompanied by an increase in keratin phosphorylation levels. Yet the mechanisms responsible for the disruption of the network structure in vivo remain poorly understood. To understand the effect of the stress-related site-specific phosphorylation of the K8:K18 pair, we created phosphomimicry mutants - K8(S431E), K8(S73E), K18(S52E) - in vitro, and investigated the various steps of keratin assembly from monomer to network structure using fluorescence and electron microscopy, and using rheology characterized their network mechanical properties. We find that the addition of a charged group produces networks with depleted intra-connectivity, which translates to a mechanically weaker and more deformable network. This large variation in network structure is achieved by the formation of shorter mutant filaments, which exhibit differing assembly kinetics and a manifestly reduced capacity to form the extended structures characteristic of the wild-type system. The similarity in outcome for all the phosphomimicry mutants explored points to a more general mechanism of structural modulation of intermediate filaments via phosphorylation. Understanding the role of kinetic effects in the construction of these cytoskeletal biopolymer networks is critical to elucidating their structure function properties, providing new insight for the design of keratin-inspired biomaterials. STATEMENT OF SIGNIFICANCE: Structural remodeling of cytoskeletal networks accompanies many cellular processes. Interestingly, levels of phosphorylation of the human soft epithelial keratin pair K8:K18 increase during their stress-related structural remodeling. Our multi-scale study sheds light on the poorly understood mechanism with which site-specific phosphorylation induces disruption of the keratin network structure in vivo. We show how phosphorylation reduces keratin filament length, an effect that propagates through to the mesoscopic structure, resulting in the formation of connectivity-depleted and mechanically weaker networks. We determine that the intrinsically-set filament-to filament attractions that drive bundle assembly give rise to the structural variability by enabling the formation of kinetically-arrested structures. Overall, our results shed light on how self-assembled intermediate filament structures can be tailored to exhibit different structural functionalities. PMID- 27403886 TI - Achieving Optimal Self-Adaptivity for Dynamic Tuning of Organic Semiconductors through Resonance Engineering. AB - Current static-state explorations of organic semiconductors for optimal material properties and device performance are hindered by limited insights into the dynamically changed molecular states and charge transport and energy transfer processes upon device operation. Here, we propose a simple yet successful strategy, resonance variation-based dynamic adaptation (RVDA), to realize optimized self-adaptive properties in donor-resonance-acceptor molecules by engineering the resonance variation for dynamic tuning of organic semiconductors. Organic light-emitting diodes hosted by these RVDA materials exhibit remarkably high performance, with external quantum efficiencies up to 21.7% and favorable device stability. Our approach, which supports simultaneous realization of dynamically adapted and selectively enhanced properties via resonance engineering, illustrates a feasible design map for the preparation of smart organic semiconductors capable of dynamic structure and property modulations, promoting the studies of organic electronics from static to dynamic. PMID- 27403887 TI - Carpal tunnel syndrome treated with guided brain plasticity: a randomised, controlled study. AB - INTRODUCTION: Guided plasticity, induced by cutaneous forearm anaesthesia, improves hand sensibility in patients with nerve injury and vibration-induced neuropathy. This study investigated whether patients with carpal tunnel syndrome (CTS) would benefit from cutaneous forearm anaesthesia. METHODS: Seventy patients with clinical and electroneurography-verified CTS were randomised to sensory training combined with either an anaesthetic cream (EMLA(r)) (n = 34) or a placebo cream (n = 36) on the volar part of the forearm. The treatment was repeated at increasing intervals over 8 weeks. The primary outcome was the Boston carpal tunnel questionnaire (BCTQ) symptom severity scale after 8 weeks. Secondary outcomes included activity limitations, sensory function, and nerve conduction. This study compared the longitudinal changes between the two groups, and with correction for multiple comparisons it also compared the longitudinal change within the groups. RESULTS: There were no significant differences in primary or secondary outcomes between the groups. However, the BCTQ symptom severity scale improved significantly within the EMLA(r) group over the 8-week period (p = 0.001). Apart from this, no significant improvements in activity limitations, sensory function, or nerve conduction were seen in the two groups compared to baseline. Altogether, 47% of patients in the EMLA(r) group and 61% in the placebo group had been operated on with carpal tunnel release by 12 months. CONCLUSION: An 8-week treatment protocol with cutaneous forearm anaesthesia to guide brain plasticity gave no significant subjective or objective improvements in hand function compared to placebo. PMID- 27403888 TI - Pristinol, a Sesquiterpene Alcohol with an Unusual Skeleton from Streptomyces pristinaespiralis. AB - A terpene cyclase from Streptomyces pristinaespiralis was characterized as the synthase for (+)-(2S,3S,9R)-pristinol. The structure of this sesquiterpene alcohol, which has a new carbon skeleton, was established by NMR spectroscopy and single-wavelength anomalous-dispersion X-ray crystallography. Extensive isotopic labelling experiments were performed to distinguish between various possible cyclization mechanisms of the terpene cyclase and to decipher the EI-MS fragmentation mechanism for pristinol. PMID- 27403889 TI - The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine. AB - Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells. PMID- 27403890 TI - The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons. AB - Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons. PMID- 27403891 TI - Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response. AB - The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-gamma secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity. PMID- 27403892 TI - Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting. AB - Synthetic access to multiple surface decorations are a bottleneck in the development of liposomes for receptor mediated targeting. This opens a complex multiparameter space, exploration of which is severely limited in terms of sample numbers and turnaround times. Here, we unlock this technological barrier by a combination of a milligram-scale liposome formulation using dual centrifugation and orthogonal click chemistry on the liposomal surface. Application of these techniques to conceptually new amphiphilic compounds, which feature norbornene and alkyne groups at the apex of sterically stabilizing, hyperbranched polyglycerol moieties, revealed a particular influence of the membrane anchor of functional amphiphiles. Folic acid residues clicked to cholesterol-based amphiphiles were inefficient in folate-mediated cell targeting, while dialkyl anchored amphiphiles remained stable in the liposomal membrane and imparted efficient targeting properties. These findings are of specific importance considering the popularity of cholesterol as a lipophilic anchor. PMID- 27403893 TI - Effect of composted sewage sludge on morpho-physiological growth parameters, grain yield and selected functional compounds of barley. AB - BACKGROUND: Several studies have evaluated the effects of composted sewage sludge on barley and found a positive influence on crop productivity. No studies have investigated the effects of composted sewage sludge on functional compounds of the caryopsis, such as phenolics and beta-glucans. The former play a role in plant defence mechanisms and both could be influenced by variations of kernel size related to fertilization intensity. The present study aimed to evaluate the effect of different doses (3-12 mg ha-1 ) of composted sewage sludge applied alone or in combination with mineral fertilization on morpho-physiological and yield qualitative parameters, especially phenolics and beta-glucans contents of grains, in barley. RESULTS: Increasing fertilization rates, irrespective of fertilizer type, improved morpho-physiological and yield parameters, whereas the phenolic compounds and the related antioxidant activity significantly decreased (P < 0.05). The beta-glucans and the main color indices did not show significant differences. The combined application of 6 mg ha-1 sewage sludge and nitrogen was not significantly different from mineral fertilization. Morpho-physiological and qualitative parameters, as well as bioactive compounds, were all significantly correlated with nutrient levels, with higher r values for nitrogen. CONCLUSION: Composted sewage sludge had a similar effect compared to mineral fertilization. (c) 2016 Society of Chemical Industry. PMID- 27403895 TI - THE DISCOVERY OF SERS: an idiosyncratic account from a vibrational spectroscopist. PMID- 27403894 TI - Rhodium-Catalyzed Regio- and Stereoselective [2 + 2] Cycloaddition of Allenamides. AB - A highly regio- and stereoselective Rh-catalyzed intermolecular head-to-head [2 + 2] cycloaddition of allenamides was developed. The intermolecular cycloadducts, trans-dimethylenecyclobutane-1,2-diamine derivatives, were achieved in good yields with high regioselectivity and stereoselectivity. PMID- 27403896 TI - Applicability of Under Vacuum Fresh Tissue Sealing and Cooling to Omics Analysis of Tumor Tissues. AB - CONTEXT: Biobanks of frozen human normal and malignant tissues represent a valuable source for "omics" analysis in translational cancer research and molecular pathology. However, the success of molecular and cellular analysis strongly relies on the collection, handling, storage procedures, and quality control of fresh human tissue samples. OBJECTIVE: We tested whether under vacuum storage (UVS) effectively preserves tissues during the time between surgery and storage for "omics" analyses. DESIGN: Normal and matched tumor specimens, obtained from 16 breast, colon, or lung cancer patients and 5 independent mesenchymal tumors, were dissected within 20 minutes from surgical excision and divided in three to five aliquots; for each tissue sample, one aliquot was snap frozen in liquid nitrogen (defined as baseline or T0 samples), and the other portions were sealed into plastic bags and kept at 4 degrees C for 1, 24, 48, or 72 hours under vacuum and then frozen. The tissue and molecular preservation under vacuum was evaluated over time in terms of histomorphology, transcription (Illumina microarrays), protein (surface-enhanced laser desorption/ionization time of flight/mass spectrometry and Western blot), and metabolic profile (nuclear magnetic resonance spectroscopy). RESULTS: Tissue morphology, Mib-1, and vimentin immunostaining were preserved over time without signs of tissue degradation. Principal variance component analysis showed that time of storage had a minimal effect on gene expression or the proteome, but affected the preservation of some metabolites to a greater extent. UVS did not impact the RNA and protein integrity or specific phosphorylation sites on mTOR and STAT3. Measurement of metabolites revealed pronounced changes after 1 hour of storage. CONCLUSIONS: Our results show that UVS can preserve tissue specimens for histological, transcriptomic, and proteomic examinations up to 48 hours and possibly longer, whereas it has limitations for metabolomic applications. PMID- 27403897 TI - Atrogin-1 Increases Smooth Muscle Contractility Through Myocardin Degradation. AB - Atrogin-1, an E3 ligase present in skeletal, cardiac and smooth muscle, down regulates myocardin protein during skeletal muscle differentiation. Myocardin, the master regulator of smooth muscle cell (SMC) differentiation, induces expression of smooth muscle marker genes through its association with serum response factor (SRF), which binds to the CArG box in the promoter. Myocardin undergoes ubiquitylation and proteasomal degradation. Evidence suggests that proteasomal degradation of myocardin is critical for myocardin to exert its transcriptional activity, but there is no report about the E3 ligase responsible for myocardin ubiquitylation and subsequent transactivation. Here, we showed that overexpression of atrogin-1 increased contractility of cultured SMCs and mouse aortic tissues in organ culture. Overexpression of dominant-negative myocardin attenuated the increase in SMC contractility induced by atrogin-1. Atrogin-1 overexpression increased expression of the SM contractile markers while downregulated expression of myocardin protein but not mRNA. Atrogin-1 also ubiquitylated myocardin for proteasomal degradation in vascular SMCs. Deletion studies showed that atrogin-1 directly interacted with myocardin through its amino acids 284-345. Immunostaining studies showed nuclear localization of atrogin-1, myocardin, and the Rpt6 subunit of the 26S proteasome. Atrogin-1 overexpression not only resulted in degradation of myocardin but also increased recruitment of RNA Polymerase II onto the promoters of myocardin target genes. In summary, our results have revealed the roles for atrogin-1 in the regulation of smooth muscle contractility through enhancement of myocardin ubiquitylation/degradation and its transcriptional activity. J. Cell. Physiol. 232: 806-817, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27403898 TI - [Fibrates - the present state of art]. AB - Peroxisome proliferator-activated receptor (PPAR)alpha activators (fibrates) are one of the major group of hypolipidemic agents. Apart from lowering plasma lipid levels, fibrates produce many other favourable effects that may potentially contribute to their clinical effectiveness. Administered to patients with abnormal glucose and lipid homeostasis participating in our studies, these agents reduced monocyte and lymphocyte secretory function, systemic inflammation, hemostasis and normalized adipose tissue function and these effects did not correlate with their lipid-lowering properties. These beneficial pleiotropic effects were observed in patients with mixed dyslipidemia, isolated hypertriglyceridemia, impaired glucose tolerance, metabolic syndrome and type 2 diabetes mellitus and their strength was similar to that of statins. However, large clinical trials assessing fibrate effectiveness in the primary and secondary prevention of cardiovascular diseases provided contrasting results. In our article, we summarise the present state of knowledge on the role of fibrates in the treatment of metabolic disorders, which leads to the conclusion that fibrates are most probably efficient in primary and secondary prevention of cardiovascular diseases, particularly in patients with mixed dyslipidemia and lipid abnormalities coexisting with disorders of carbohydrate metabolism. PMID- 27403899 TI - [Evaluation of changes in the central and peripheral circulatory system under the influence of physical training carried out under the standard procedure of improving patients after acute coronary syndrome]. AB - The observed with age, atherosclerotic changes in vessels and increasing damage to the vascular endothelium, causing an increase in the occurrence of cardiovascular events. An important element in the rehabilitation of patients with coronary artery disease is a physical activity, to complement the pharmacological treatment. AIM: The aim of the study was to evaluate the influence of a controlled exercise training on changes in central and peripheral circulatory system in patients after acute coronary syndrome. MATERIALS AND METHODS: Group comprising 92 patients were divided into three subgroups. The rehabilitation period ranged from 2 to 4 weeks. In group I and II performed a series of interval training on a bicycle ergometer supplemented by general conditioning exercises; in the group III training individually tailored program, consisting of breathing exercises, relaxation and small muscle groups. In all groups, before and after the training cycle test was performed impedance plethysmography of the chest, echocardiography, exercise test. RESULTS: After completing the program, the parameters plethysmography improved in all groups, with the largest changes were observed in the group treated to the longest training: increase PAmpl (pulse wave amplitude) of 16.7% and PSlope (systolic slope) of 17.6%, while decline in the value of CT (crest time) by 5.7% and PT (propagation time) by 6.3%. In groups, which carried out a controlled exercise training have improved as well: exercise capacity of patients, stroke volume SV, cardiac output CO and global myocardial contractility EF. Moreover, a correlation between the results plethysmography parameters and SV, CO and EF. CONCLUSIONS: Controlled physical training, which comes under the standard procedure rehabilitation of patients after acute coronary syndrome, leads to better blood perfusion in vessels of the legs and improve myocardial functional parameters, thereby affecting the growth of physical capacity of patients. PMID- 27403900 TI - [The use of controlled physical training in patients with acute coronary syndrome treated with intervention - assessment of effects on biochemical parameters and functional myocardial]. AB - Diseases of the cardiovascular system is one of the most common causes of death among people over 65 years. Due to its course and incidence are a major cause of disability and impaired quality of life for seniors, as well as a serious economic problem in health care. Important role in the prevention of cardiovascular disease plays making systematic physical activity, which is a component of any rehabilitation program. Regular physical training by doing cardio-and vasoprotective has a beneficial effect on cardiovascular status and physical performance in patients with diagnosed coronary heart disease, regardless of age. AIM: The aim of this study was to evaluate the effect of controlled exercise on selected biochemical parameters and functional myocardial infarction. MATERIALS AND METHODS: A group of 89 patients were divided into 3 subgroups. In group I (n = 30) was performed 2 weeks cardiac rehabilitation program, in group II (n = 30) 4 weekly. Streamline the program consisted of a series of interval training performed using a bicycle ergometer and general exercise. The remaining group (gr. III, n = 29) participated in individually selected training program. In all subjects before and after the training cycle underwent thoracic impedance plethysmography, also determined the level of plasma natriuretic peptide NT-proBNP and echocardiography and exercise test. RESULTS: After training, in groups, which carried out a controlled physical training, improvement was observed: exercise capacity of patients respectively in group I (p = 0.0003), group II (p = 0.0001) and group III (p = 0.032), stroke volume SV, cardiac output CO and global myocardial contractility, there was also reduction in the concentration of natriuretic peptide NT-proBNP. Furthermore, the correlation between the results shown pletyzmography parameters and NT-proBNP, SV, CO and EF. CONCLUSIONS: Regular physical training as part of the cardiac rehabilitation has a beneficial effect on biochemical parameters and functional myocardial infarction in patients with ACS. Size of the observed changes conditioned by the nature and duration of the training. PMID- 27403901 TI - [Motor levodopa-induced complications in Parkinson's disease]. AB - Chronic treatment with levodopa in Parkinson's disease (PD) is associated with the risk of development of motor fluctuations and dyskinesias, i.e. motor levodopa-induced complications (MLIC). AIM: The aim of the study was to investigate factors influencing prevalence of MLIC in PD patients. MATERIALS AND METHODS: 76 patients with idiopathic PD were included in the study. Theirs mean disease duration was 10,33 years and mean levodopa therapy duration was 8,65 years. The most common drug regimen was levodopa with ropinirole. The patients were evaluated using Hoehn and Yahr scale, UPDRS II, III, and were qualified for 4 clinical subtypes according to van Rooden at al. classification. RESULTS AND CONCLUSIONS: The prevalence of MLIC was 54% with their mean duration of 3,34 years. MLIC were influenced by higher levodopa equivalent dose, younger age at onset, younger age, longer disease duration, and longer levodopa therapy regardless of PD clinical subtype. Although women had more advanced disease according to Hoehn and Yahr score, sex did not influence MLIC. The incidence of MLIC in both sexes was probably leveled by inclusion of sex as a risk factor of MLIC in treatment strategy. Therefore modifiable MLIC risk factors should be investigated in different PD populations. PMID- 27403902 TI - [Effect of treatment with diet on reducing levels of sex hormones in perimenopausal women with overweight and obesity]. AB - Nowadays, fight against obesity is a big challenge for the developed countries. Perimenopausal women are especially prone to becoming overweight and obese. This is due to changes in hormone levels and alterations in the sex hormones synthesis pathway. AIM: The aim of this study was to evaluate the levels of sex hormones in overweight and obese women during menopause following the three month period of reducing diet. MATERIALS AND METHODS: The study involved women aged 55+/-4,75 years. Group I - 33 overweight women (BMI 28,06+/-1,00 kg/m(2)). Group II - 32 obese women (BMI 34,22+/-3,79 kg/m(2)). Anthropometric measurements, body composition tested with Bodystat QuadScan 4000 analyzer and levels of sex hormones in the blood was determined before and after the three-months of reducing diet in both groups. Statistical data analysis was performed. RESULTS: After three-months of reducing diet it was noticed that levels of BMI, body fat, FSH, DHEA-S and androstenedione were decreased in a statistically significant manner. A significant increase in estradiol levels after reduction of visceral adipose tissue in both groups, overweight and obese women, was observed. However, only in the group of obese women, a decrease in BMI correlated with a significant increase in estradiol levels. CONCLUSIONS: Application of appropriate reducing diet in perimenopausal overweight and obese women has positive impact on visceral adipose tissue distribution and causes an increase in sex hormones levels. Perimenopausal overweight and obese women should pursue weight reduction to improve their chances of contracting cardiovascular diseases. PMID- 27403903 TI - [Influence of ET-1 and ETA receptor blocker (BQ123) on the level of TNF-alpha in the brain rat]. AB - Endothelin 1 (ET-1) in addition to the vasoconstriction, also has mitogenic, proinflammatory and proagregation activities. The mediators of inflammatory responses are cytokines, including special role attributed to tumor necrosis factor (TNF-alpha). AIM: The aim of this study was to evaluate the effect of ET-1 and its receptor blocker (BQ123) on the level of TNF-alpha in the brain rat. MATERIALS AND METHODS: Experiments were performed on four groups of Wistar-Kyoto rats. Animals were divided into four groups of 8 rats. Group I - control was administered into the tail vein solution of 0.9 % NaCl. Group II - saline followed by ET-1 (3 MUg/kg b.w.). Group III - saline followed by BQ123 (1 mg/kg b.w.). Group IV (BQ123/ET-1) - BQ123 (1 mg/kg b.w.) administered 30 min before ET 1 (3 MUg/kg b.w.). RESULTS: Administration of ET-1 at doses of 3 MUg/kg b.w. resulted in a statistically significant increase in TNF-alpha concentrations in brain homogenates compared to the control group (p<0.01). Administration of the ET(A) receptor blocker - BQ123 (1mg/kg b.w.) 30 min before administration of ET-1 significantly decreased in TNF-alpha concentrations in brain homogenates (p <0.01). CONCLUSIONS: ET-1 is significantly increased in TNF-alpha levels in brain homogenates, while BQ123 given 30 min before administration of ET-1 caused a significant decrease in TNF-alpha levels, suggesting that its anti-inflammatory activity. PMID- 27403904 TI - [Takotsubo cardiomyopathy in a young woman after a traffic accident with blunt chest trauma]. AB - Takotsubo cardiomyopathy (TC) is characterized as an acute, reversible left ventricular dysfunction which may be triggered by mental or physical stress. In the case of a 32-year-old woman severe heart failure was observed after a traffic accident with blunt chest trauma. ECG showed ST changes mimicking acute myocardial infarction; although, echocardiography revealed a profile of left ventricular contractile disturbances typical of TC, with ejection fraction reduced to 20%. Additionally, repeated echocardiography showed transient left ventricular wall thickness, suggestive of myocardial edema. Recovery to normal heart function and morphology was confirmed in cardiovascular magnetic resonance. Coronary arteries potency was verified in multi-slice computed tomography. Summing up, it seems that TC should be included in differential diagnosis of heart failure in posttraumatic patients; however, it is impossible to say conclusively which factor was dominant in TC pathogenesis in the case presented: emotional stress or chest trauma. PMID- 27403905 TI - [Abdominal symptoms necessitating surgical intervention as the initial presentation of Henoch-Schonlein purpura in children - case reports]. AB - Henoch-Schonlein purpura (HSP) is the most common pediatric autoimmune vasculitis. Gastrointestinal symptoms of HSP including abdominal pain, diarrhea, and vomiting may precede skin changes by several days. We present diagnostic challenges in two adolescents with HSP and severe abdominal symptoms necessitating surgical intervention before the development of skin changes. CASE REPORT 1: A 15-year old boy with 7 day history of abdominal pain, and bloody vomiting (1-2 x per day) without diarrhea. A suspicion of acute appendicitis was raised and the boy was operated on the 7th day since the initial symptoms. The appendix showed some reactive inflammation and was removed during laparotomy which also revealed enlarged mesenteric lymph nodes and a modest amount of fluid in the pelvic cavity. During the first day after the surgery, skin changes typical for HSP developed on lower limbs and buttocks. CASE REPORT 2: A 12-year old girl with 7 day history of abdominal pain, without diarrhea or vomiting. On the day of admission hemorrhagic rash appeared on lower limbs. Laparotomy was performed on 14th day after onset of abdominal pain - large amounts of serous, blood-stained fluid, massive dilation of small intestine with ecchymoses in mucous membrane, segmental infiltration and stiffening of intestinal wall were found. Normal appendix was removed. CONCLUSIONS: Severe abdominal symptoms may precede skin changes in children with HSP, resulting in diagnostic and therapeutic challenges. When considering laparotomy in children with an atypical "acute abdomen" presentation, other manifestations of HSP should be sought. PMID- 27403906 TI - [The relation between the low T3 syndrome in the clinical course of myocardial infarction and heart failure]. AB - It has been proven that either excess or deficiency of thyroid hormones has harmful influence on the cardiovascular system function. On the other hand, severe systemic conditions like myocardial infarction or severe heart failure may affect thyroid hormones secretion and their peripheral conversion, leading to low T3 syndrome. Amongst many mechanisms causing T4 to T3 conversion disturbances, important role plays decreased activity of D1 deiodinase and increased activity of D3 deiodinase. The animal research confirmed that thyroid hormones influence cardiomiocytes phenotype and morphology. They inhibit inflammation, apoptosis and cardiac remodelling after myocardial infarction. It was also proven that free triiodothyronine similarly to brain natriuretic peptide predict long-term prognosis in chronic and acute heart failure patients. Potential influence of low T3 syndrome on the course of myocardial infarction and heart failure may have significant impact on the future research on individualization of myocardial infarction and heart failure treatment depending on patient's thyroid status. PMID- 27403907 TI - [Hygienic hypothesis in immunopathogenesis of inflammatory bowel disease]. AB - Over three last decades, it has been noticed that morbidity of immunology dependent illnesses, like asthma, inflammatory bowel disease or atopic dermatitis, apparently increased. That is the reason to focus on searching and exploring new ideas which could explain etiopathology of those diseases. In etiopathology the role of environmental factors is particularly emphasized. Research indicated the inverse relationship between the frequency of infectious and/ or parasites and autoimmune diseases. It was a leading subject of many studies what allowed to create a hypothesis which explains the phenomenon. The most original and innovative idea, named hygenic hypothesis, was proposed in the late 80s of the last century. Avoiding or limiting the contact with common bacteria and parasites in well-and very well-developed countries probably caused depletion of immune memory which resulted in the hypersensitive response after exposure to general factors. Nowadays, autoimmunological diseases make really serious problem for medical care in the United States of America and Western European countries, ranking just behind cardiovascular diseases, cancer and metabolic sicknesses. PMID- 27403908 TI - [Evaluation of repetitive transcranial magnetic stimulation effectiveness in treatment of psychiatric and neurologic diseases]. AB - Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness especially in drug resist depression. It is used in functional brain mapping before neurosurgery operations and diagnostic of corticospinal tract transmission. Many studies are performed to evaluate rTMS using in treatment of obsessive - compulsive disorder, schizophrenia, autism, strokes, tinnitus, Alzheimer and Parkinson diseases, cranial traumas. Moreover rTMS was used in treatment of multiple sclerosis, migraine, dystonia. Electromagnetical field generated by rTMS penetrate skin of the scalp and infiltrate brain tissues to a depth of 2 cm, cause neurons depolarization and generating motor, cognitive and affective effects. Depending on the stimulation frequency rTMS can stimuli or inhibit brain cortex. rTMS mechanism of action remains elusive. Probably it is connected with enhancement of neurotransmitters, modulation of signals transductions pathways in Central Nervous System, gene transcription and release of neuroprotective substances. Studies with use of animals revealed that rTMS stimulation can generate brain changes similar to those seen after electric shock therapy without provoking seizures. The aim of presenting study was to analyze actual researches evaluating rTMS use in treatment of psychiatric and neurological diseases. PMID- 27403909 TI - [Fibroblast growth factor 23 in chronic kidney disease in children]. AB - Cardiovascular risk in children with chronic kidney disease (CKD) is many times higher compared to their healthy peers, and discovered in year 2000 fibroblast growth factor 23 (FGF23) may be one of the factors responsible. FGF23 together with its cofactor, alpha-Klotho protein, plays a pivotal role in calcium phosphorus metabolism in patients with CKD by decreasing secretion of active metabolite of vitamin D and antagonizing phosphate resorption in renal tubules. Studies conducted in recent years revealed that FGF23 directly binds to its receptor on cardiomyocytes and promotes left ventricular hypertrophy. Clinical trials in children with CKD, similarly to adult studies, suggest a key role of this protein in development of calciumphosphorus disturbances. Single studies in small patient groups suggest also a significance of FGF23 in pathogenesis of cardiovascular alterations in this population. Further clinical trials investigating role of FGF23 in development of cardiovascular damage in larger groups of children are necessary, which may open new therapeutic options for these patients in future. PMID- 27403910 TI - A dipeptide-based superhydrogel: Removal of toxic dyes and heavy metal ions from waste water. AB - A short peptide-based molecule has been found to form a strong hydrogel at phosphate buffer solution of pH 7.46. The hydrogel has been characterized thoroughly using various techniques including field emission scanning electron microscopy (FE-SEM), wide angle powder X-ray diffraction (PXRD), and rheological analysis. It has been observed from FE-SEM images that entangled nanofiber network is responsible for gelation. Rheological investigation demonstrates that the self-assembly of this synthetic dipeptide results in the formation of mechanically strong hydrogel with storage modulus (G') around 104 Pa. This gel has been used for removing both cationic and anionic toxic organic dyes (Brilliant Blue, Congo red, Malachite Green, Rhodamine B) and metal ions (Co2+ and Ni2+ ) from waste water. Moreover, only a small amount of the gelator is required (less than 1 mg/mL) for preparation of this superhydrogel and even this hydrogel can be reused three times for dye/metal ion absorption. This signifies the importance of the hydrogel towards waste water management. PMID- 27403912 TI - Is elimination of HCV possible in a country with low diagnostic rate and moderate HCV prevalence?: The case of Greece. AB - BACKGROUND AND AIM: The treatment of hepatitis C (HCV) with interferon (IFN)-free direct-acting antivirals (DAAs) is anticipated to change the future burden of disease. The aim of this study is to quantify the impact of IFN-free DAAs on HCV related morbidity and mortality in Greece under different scenarios concerning treatment coverage and primary prevention, including the proposed by World Health Organization Global Hepatitis Strategy. METHODS: A previously described model was used to project the future disease burden up to 2030 under scenarios, which includes treatment based on the combination of pegylated-IFN with ribavirin (base case) and scenarios using DAAs therapies. RESULTS: Under the base case scenario, an increase in HCV-related morbidity and mortality is predicted in Greece (mortality in 2030: +23.6% compared with 2015). If DAAs are used with the same treatment coverage, the number of hepatocellular carcinoma cases and of liver related deaths are predicted to be lower by 4-7% compared with 2015. Under increased treatment coverage (from 2000 treated/year to approximately 5000/year in 2015-2020 and 2500/year subsequently), morbidity and mortality will decrease by 43-53% in 2030 compared with 2015. To achieve the WHO Global Hepatitis Strategy goals, a total number of 86 500 chronic hepatitis C patients will have to be treated during 2015-2030. CONCLUSIONS: Elimination of HCV in Greece by 2030 necessitates great improvements in primary prevention, implementation of large screening programs and high treatment coverage. PMID- 27403913 TI - The Relationship Between Metformin and Serum Prostate-Specific Antigen Levels. AB - BACKGROUND: Metformin is the first-line oral antihyperglycemic of choice for individuals with type 2 diabetes. Recent evidence supports a role for metformin in prostate cancer chemoprotection. However, whether metformin indeed influences prostate biology is unknown. We aimed to study the association between metformin and serum prostate-specific antigen (PSA) levels-the primary prostate cancer biomarker. METHODS: We conducted a cross-sectional study of 326 prostate cancer free men with type 2 diabetes were recruited between 2004 and 2013 at St. Michael's Hospital. Men were excluded if they had a PSA >=10-ng/ml, or used >2,550-mg/d metformin or supplemental androgens. Multivariate linear regressions quantified the association between metformin dose and log-PSA. Secondary analyses quantified the association between other antihyperglycemics (sulfonylureas, thiazolidinediones) and PSA; sensitivity analyses tested covariate interactions. RESULTS: Median PSA was 0.9-ng/ml (IQR: 0.5-1.6-ng/ml). Metformin dose associated positively with BMI, HbA1c, diabetes duration, and number of statin, acetylsalicylic acid, diuretic users, and number of antihyperglycemics used, and negatively with LDL-C. In multivariate models, PSA changed by -8% (95%CI: -13 to 2%, P = 0.011) per 500-mg/d increase in metformin. Men with diabetes for >=6 years (n = 163) saw a greater difference in PSA per 500-mg/d metformin (-12% [95% CI: -19 to -4%, P = 0.002], P-interaction = 0.018). Serum PSA did not relate with sulfonylureas, thiazolidinediones, or total number of antihyperglycemic agents used. Our findings are limited by the cross-sectional design of this study. CONCLUSIONS: Metformin dose-dependently inversely associated with serum PSA, independent of other antihyperglycemic medications. Whether metformin confers a dose-dependent benefit on prostate tumorigenesis and progression warrants investigation. Prostate 76:1445-1453, 2016. (c) 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID- 27403914 TI - Mortality Trends of Acute Respiratory Distress Syndrome in the United States from 1999 to 2013. AB - RATIONALE: Acute respiratory distress syndrome (ARDS) is an acute hypoxemic respiratory failure seen in critically ill patients after an inciting injury. The burden of ARDS mortality in the United States in recent years is not well characterized. OBJECTIVES: In this study, we aimed to describe trends in the annual incidence of ARDS mortality in the United States from 1999 to 2013. We also describe demographic characteristics, geographic and seasonal trends, and other associated underlying causes of death in this population. METHODS: Data on all deceased U.S. residents are available through the Multiple Cause of Death (MCOD) database of the National Center for Health Statistics. ARDS-related deaths were identified in the MCOD database using International Classification of Diseases, 10th Revision. MEASUREMENTS AND MAIN RESULTS: Aggregate annual crude and age-adjusted mortality rates and mortality rate ratios were used to compare various demographic subpopulations. Over the 15-year period, the national ARDS related age-adjusted mortality rate demonstrated an annual seasonal variation, peaking in winter. The annual rate decreased in a nonlinear fashion, with a plateau from 2010 to 2013. The ARDS-related age-adjusted mortality rate was 5.01 per 100,000 persons (95% confidence interval, 4.92-5.09) in 1999 and 2.82 per 100,000 persons (95% confidence interval, 2.76-2.88) in 2013. Males had a higher average ARDS-related mortality rate than did females. Asian/Pacific Islanders had the lowest average age-adjusted ARDS-related mortality rate, and black/African American individuals, the highest. CONCLUSIONS: National age-adjusted ARDS related mortality rates decreased between 1999 and 2013 in the United States, yet still show relative racial and sex disparities. However, death certificates largely underestimate the overall mortality burden from ARDS when compared with studies of clinically ascertained cases. PMID- 27403915 TI - Radiographic Results and Complications of 3 Guided Growth Implants. AB - BACKGROUND: Temporary, implant-mediated hemiepiphysiodesis (ie, guided growth) is an effective and popular treatment method for lower extremity angular deformities. The purpose of this study was to retrospectively evaluate the safety profile of 3 different implants used to correct lower extremity angular deformities in pediatric patients. METHODS: We retrospectively reviewed a consecutive series of pediatric patients with lower extremity angular deformities who underwent implant-mediated guided growth by 2 surgeons at our institution between 2004 and 2014. Implants were selected according to surgeon preference and included the Biomet peanut plate, Orthofix eight-plate, and Pega Medical hinge plate. Medical records and radiographs were reviewed to assess deformity correction, implant integrity, and complications. RESULTS: During the study period, 115 plates (63 Biomet peanut plates, 30 Orthofix eight-plates, and 22 Pega Medical hinge plates) were implanted in 52 patients (24 males, 28 females). Average age at implantation was 11.7 years (12.3 y in males, 11.1 y in females). Average length of follow-up was 18.4 months. There was no significant difference in rate of deformity correction between the implant types (P=0.08).Three broken screws (2.6%) were observed, all of which involved cannulated screws in peanut plates. Four peanut plates (6.3%) had an implant-related complication: 3 broken screws and 1 screw pullout. Three eight-plates (10.0%) had screw pullout. No complications were observed within either the hinge plate or solid screw groups. Implant-related complications were significantly associated with increased body weight and cannulated screw use (P=0.02 and 0.03, respectively), but not bone age, sex, plate type, or rate of deformity correction. No deep infections, premature growth arrests, or plate breakages were observed. CONCLUSIONS: Implant mediated guided growth is a safe technique for pediatric lower extremity angular deformity correction with a low complication rate. This study demonstrated that overweight patients had a significantly higher rate of implant-related complications. Screw breakages were only observed with cannulated screws in peanut plates. Thus, we recommend using solid, noncannulated screws in overweight children who are at an increased risk of implant failure. LEVEL OF EVIDENCE: Level IV-retrospective case series. PMID- 27403916 TI - Surgical Management of Progressive Thoracolumbar Kyphosis in Mucopolysaccharidosis: Is a Posterior-only Approach Safe and Effective? AB - BACKGROUND: According to the current literature, the recommended surgical treatment is circumferential spinal fusion, including both anterior and posterior procedures, for progressive thoracolumbar kyphosis in mucopolysaccharidosis (MPS). The purpose of this study was to report our experience with the posterior only approach and instrumented fusion for MPS kyphosis. METHODS: Six consecutive patients with MPS and thoracolumbar junctional kyphosis managed with the posterior-only approach were included. Demographic data, the type of MPS, medical comorbidities, and accompanying clinical manifestations were recorded. Measurements recorded on radiographs for the study included the presence of any coronal-plane deformity, fusion levels, changes in the local kyphosis angle (LKA), proximal and distal junctional kyphosis angles, and the apical vertebral wedge angle. RESULTS: The average age at the time of surgery was 6.6 (range, 4 to 12) years. The average follow-up duration was 52.6 (range, 44 to 64) months. The mean preoperative LKA of 63.1+/-15.8 (range, 48 to 92) degrees decreased to a mean of 16.6+/-8.4 (range, 5 to 30) degrees immediately after surgery. At the latest follow-up, the mean LKA was 19.6+/-8.8 (range, 8 to 34) degrees. Apical vertebral listhesis was reduced in all patients with surgical correction. The average apical vertebral wedge angle of 15 (range, 11 to 19) degrees at the early postoperative period decreased to 4.6 (range, 2 to 7) degrees at the latest follow-up. Adjacent-segment problems occurred in 2 patients. There were no neurological complications or implant failures in any of the patients. CONCLUSIONS: Posterior-only corrective techniques and instrumented fusion with pedicle screws for progressive thoracolumbar junctional kyphosis in MPS patients are safe and effective methods. Its results are comparable to those achieved with conventional circumferential fusion. However, patients should be monitored closely for adjacent-segment problems. LEVEL OF EVIDENCE: Level IV-retrospective case series. PMID- 27403917 TI - What's New in Pediatric Spine Growth Modulation and Implant Technology for Early Onset Scoliosis? AB - BACKGROUND: Early-onset scoliosis (EOS) affects roughly 1 to 2 out of 10,000 live births per year. Because this subset of patients has a yet to achieve a majority of their skeletal growth, a number of treatment challenges need to be addressed before surgical intervention. If left untreated, EOS can cause a number of problems throughout the patient's lifespan, particularly in regards to the growth of the thorax and pulmonary development. A wide variety of surgical systems and techniques are available to the treating surgeon. METHODS: A review of the orthopaedic literature from 2010 to 2015 relating to pediatric spine growth modulation was performed. Ninety-eight papers were identified and, following exclusion criteria, a total of 31 papers were selected for further review. RESULTS: This paper summarizes the recently published literature regarding growth friendly spinal implants, the status of their Food and Drug Administration approval labeling as well as the indications, applications, and complications associated with their implementation. CONCLUSIONS: There are a growing number of options at the surgeon's disposal when treating patients with EOS. As surgeons, we must continue to be vigilant in our demand for sound clinical evidence as we strive to provide optimal care for our patients. The rapidly advancing field of spinal growth modulation is exciting. More work must be done to further enhance our ability to predictably modulate growth in the pediatric spine. PMID- 27403918 TI - A Dozen Tips for Getting Published. PMID- 27403919 TI - Head Injuries in Soccer. AB - Soccer is currently the most popular and fastest growing sport worldwide, with approximately 265 million registered soccer players existing around the world. The popularity of the sport, coupled with the high incidence of 18.8-21.5 head injuries per 1,000 player hours reported, make it essential that clinicians, coaches, and the athletes, have a solid understanding of head injuries. The successful rehabilitation of athletes with head injuries relies upon early and accurate identification strategies and implementation of appropriate return to play measures across all areas in the continuum of care. CLINICAL RELEVANCE: Soccer is a frequently played sport, and head injuries are common. Therefore, it is imperative that clinicians, coaches, and the athletes themselves have a solid understanding of head injury prevention, diagnosis, and treatment options. The purpose of this article was to provide rehabilitation nurses with current information regarding frequently occurring head injuries in the widespread sport of soccer. PMID- 27403920 TI - Use of the Pressure Ulcer Scale for Healing (PUSH) in Inpatient Rehabilitation: A Case Example. AB - PURPOSE: Nurses who specialize in rehabilitation frequently assess and treat patients with pressure ulcers. The purpose of this case study is to describe the use of the Pressure Ulcer Scale for Healing (PUSH), which has demonstrated excellent psychometric properties, to assess, monitor progress, and guide clinical decision-making during inpatient rehabilitation. METHODS: The psychometric properties, clinical utility, and data that can be used to interpret the results of the PUSH instrument are presented. Application of the instrument in clinical practice is also described. FINDINGS AND CONCLUSIONS: Systematic measurement of a pressure ulcer using the PUSH has potential to demonstrate change in pressure ulcer status that results from clinical treatment. This case provides an example of how results of a clinical assessment can effectively guide clinical decisions. PMID- 27403921 TI - Effect of amoxicillin exposure on brain, gill, liver, and kidney of common carp (Cyprinus carpio): The role of amoxicilloic acid. AB - Amoxicillin (AMX) is one of the most commonly prescribed antibiotics around the world due to its broad-spectrum activity against different bacterial strains as well as its use as a growth promoter in animal husbandry. Although residues of this antibacterial agent have been found in water bodies in diverse countries, there is not enough information on its potential toxicity to aquatic organisms such as the common carp Cyprinus carpio. This study aimed to evaluate AMX-induced oxidative stress in brain, gill, liver and kidney of C. carpio. Carp were exposed to three different concentrations of AMX (10 ng/L, 10 MUg/L, 10 mg/L) for 12, 24, 48, 72, and 96 h, and the following biomarkers were evaluated: lipid peroxidation (LPX), hydroperoxide content (HPC), protein carbonyl content (PCC) and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Amoxicillin and its main degradation product amoxicilloic acid (AMA) were determined by high performance liquid chromatography coupled with electrochemical detection and UV detection (HPLC-EC-UV). Significant increases in LPX, HPC, and PCC (P < 0.05) were found in all study organs, particularly kidney, as well as significant changes in antioxidant enzymes activity. Amoxicilloic acid in water is concluded to induce oxidative stress in C. carpio, this damage being highest in kidney. The biomarkers used are effective for the assessment of the environmental impact of this agent on aquatic species. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1102-1120, 2017. PMID- 27403922 TI - Fully Mechanically Controlled Automated Electron Microscopic Tomography. AB - Knowledge of three-dimensional (3D) structures of each individual particles of asymmetric and flexible proteins is essential in understanding those proteins' functions; but their structures are difficult to determine. Electron tomography (ET) provides a tool for imaging a single and unique biological object from a series of tilted angles, but it is challenging to image a single protein for three-dimensional (3D) reconstruction due to the imperfect mechanical control capability of the specimen goniometer under both a medium to high magnification (approximately 50,000-160,000*) and an optimized beam coherence condition. Here, we report a fully mechanical control method for automating ET data acquisition without using beam tilt/shift processes. This method could reduce the accumulation of beam tilt/shift that used to compensate the error from the mechanical control, but downgraded the beam coherence. Our method was developed by minimizing the error of the target object center during the tilting process through a closed-loop proportional-integral (PI) control algorithm. The validations by both negative staining (NS) and cryo-electron microscopy (cryo-EM) suggest that this method has a comparable capability to other ET methods in tracking target proteins while maintaining optimized beam coherence conditions for imaging. PMID- 27403923 TI - SEMA3A suspended in matrigel improves titanium implant fixation in ovariectomized rats. AB - The aim of this study was to evaluate the effect of SEMA3A released from matrigel on implant fixation in ovariectomized (OVX) rats. Sixty female rats were subjected to bilateral ovariectomy. Twelve weeks later, rats were randomly divided into three groups according to implants they accepted: (1) Control, implants with distilled water; (2) Matrigel, implants with matrigel coating; (3) Matrigel + SEMA3A, implants with coating of SEMA3A suspended in matrigel. Implants were inserted in metaphysis of proximal tibiae in all animas bilaterally. In vitro release of SEMA3A was tested using enzyme linked immunosorbent assay. In vitro release of SEMA3A was detectable during the first 10 days, and a burst release of was observed during the first 3 days. No significant difference was observed between Control and Matrigel group. The protective effects of SEMA3A in matrigel on peri-implant bone, implant osseointegration and fixation was confirmed. Compared to matrigel alone, SEMA3A suspended in matrigel increased percent bone volume by 88.7% and 83.3% (p < 0.01), bone-to-implant contact ratio by 148.9% (p < 0.01), and 24.8% (p < 0.05), the maximal push-out force by 149.3% and 209.2% (p < 0.01) at 4 and 8 weeks after implant insertion, respectively. Surface modification with SEMA3A suspended in matrigel improved implant osseointegration and fixation in the proximal tibiae of OVX rats. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2060-2065, 2017. PMID- 27403925 TI - A mechanistic insight into the effect of piperidine as an organocatalyst on the [3 + 2] cycloaddition reaction of benzalacetone with phenyl azide from a computational study. AB - Several transition structures (TSs) for catalyst-free [3 + 2] cycloaddition and two plausible mechanistic pathways for the organocatalyzed [3 + 2] cycloaddition (32CA) between benzalacetone and phenyl azide were located by quantum chemistry methods. Calculations were carried out with B3LYP, MPWB1K and M06-2X functionals using 6-31G(d) and 6-311G(d,p) basis sets in gas and solvent phases. The calculated activation barriers imply that the lowest barrier pathway is the catalyzed process producing 3-regioisomers through the iminium intermediate and not through the dienamine route. Electronic displacements along the reaction path have been examined using a topological analysis of the electron-localization function (ELF). ELF topological analyses along the intrinsic reaction coordinates (IRC) of both catalyzed and uncatalyzed 32CA reactions indicated that while the first C1-N1 single bond is formed as a dative bond, the formation of the second C2-N3 bond takes place via a C-to-N coupling between the interacting centers of the reagents. Moreover, the ELF analyses imply that the reaction mechanism is a two-stage one-step process in the presence of a piperidine organocatalyst, while bond formation in an uncatalyzed process is almost synchronous. PMID- 27403924 TI - Disrupted topological organization of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis. AB - The brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS. PMID- 27403926 TI - Collaboration enhances later individual memory for emotional material. AB - Research on collaborative remembering suggests that collaboration hampers group memory (i.e., collaborative inhibition), yet enhances later individual memory. Studies examining collaborative effects on memory for emotional stimuli are scarce, especially concerning later individual memory. In the present study, female undergraduates watched an emotional movie and recalled it either collaboratively (n = 60) or individually (n = 60), followed by an individual free recall test and a recognition test. We replicated the standard collaborative inhibition effect. Further, in line with the literature, the collaborative condition displayed better post-collaborative individual memory. More importantly, in post-collaborative free recall, the centrality of the information to the movie plot did not play an important role. Recognition rendered slightly different results. Although collaboration rendered more correct recognition for more central details, it did not enhance recognition of background details. Secondly, the collaborative and individual conditions did not differ with respect to overlap of unique correct items in free recall. Yet, during recognition former collaborators more unanimously endorsed correct answers, as well as errors. Finally, extraversion, neuroticism, social anxiety, and depressive symptoms did not moderate the influence of collaboration on memory. Implications for the fields of forensic and clinical psychology are discussed. PMID- 27403928 TI - A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing's Syndrome. AB - CONTEXT: To date, all the familial hyperaldosteronism type III (FH-III) patients reported presenting with typical primary aldosteronism (PA), without showing other adrenal hormone abnormalities. OBJECTIVE: This study characterized a novel phenotype of FH-III and explored the possible pathogenesis. PATIENTS AND METHODS: A male patient presented with severe hypertension and hypokalemia at the age of 2 years and developed Cushing's syndrome at 20 years. He was diagnosed with PA and Cushing's syndrome on the basis of typical biochemical findings. He had massive bilateral adrenal hyperplasia and underwent left adrenalectomy. KCNJ5 was sequenced, and secretion of aldosterone and cortisol were observed both in vivo and in vitro. RESULTS: A heterozygous germline p.Glu145Gln mutation of KCNJ5 was identified. ARMC5, PRKAR1A, PDE8B, PDE11A, and PRKACA genes and beta-catenin, P53 immunoactivity were normal in the adrenal. CYP11B2 was highly expressed, whereas mRNA expression of CYP11B1, CYP17A1, and STAR was relatively low in the hyperplastic adrenal, compared with normal adrenal cortex and other adrenal diseases. In the primary cell culture of the resected hyperplastic adrenal, verapamil and nifedipine, two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol and the mRNA expression of CYP11B1, CYP11B2, CYP17A1, and STAR. CONCLUSIONS: We presented the first FH-III patient who had both severe PA and Cushing's syndrome. Hypersecretion of cortisol might be ascribed to overly large size of the hyperplastic adrenal because CYP11B1 expression was relatively low in his adrenal. Like aldosterone, synthesis and secretion of cortisol in the mutant adrenal may be mediated by voltage-gated Ca2+ channels. PMID- 27403927 TI - The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene. AB - BACKGROUND: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. OBJECTIVE: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. METHODS: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. RESULTS: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16 years) and 22 years (range, 16 to 52 years), respectively. Of the cohort, 29 men (56%) had 20 different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P = .004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. CONCLUSIONS: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management. PMID- 27403929 TI - Sex Hormones and Sleep in Men and Women From the General Population: A Cross Sectional Observational Study. AB - CONTEXT AND OBJECTIVES: Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. DESIGN, SETTING, AND PARTICIPANTS: We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. MAIN OUTCOME AND MEASURES: Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. RESULTS: In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46-0.83), free T, and SHBG with AHI were rendered nonsignificant after multivariable adjustment. In multivariable analyses, ASD was associated with Epworth Sleepiness Scale (beta-coefficient per SD increase in ASD: -0.71; 95% CI: -1.18 to -0.25). In women, multivariable analyses showed positive associations of dehydroepiandrosterone-sulphate with wake after sleep onset (beta-coefficient: .16; 95% CI 0.03-0.28) and of E2 and E2 to TT ratio with Epworth Sleepiness Scale. Additionally, free T and SHBG were associated with AHI in multivariable models among premenopausal women. CONCLUSIONS: The present cross-sectional, population-based study observed sex specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness. However, multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep. PMID- 27403930 TI - Type 1 Hyperlipoproteinemia Due to Compound Heterozygous Rare Variants in GCKR. AB - BACKGROUND: Type 1 hyperlipoproteinemia (T1HLP) is a rare, autosomal recessive disorder characterized by extreme elevations in serum triglyceride (TG) levels. Despite considerable progress in identifying several causal genes for T1HLP, such as LPL, APOC2, APOA5, LMF1, and GPIHBP1, the molecular basis of some extremely rare patients presenting with T1HLP remains obscure. CASE DESCRIPTION: We report a 58-year-old Hispanic female who initially presented with serum TG of 4740 mg/dL at age 23 years when she was 3 weeks postpartum and was taking an oral contraceptive for 2 weeks. Over a period of 35 years, she has had recurrent episodes of extreme hypertriglyceridemia (fasting serum TG exceeding 2000 mg/dL), which responded to a reduction of dietary fat, fibrates, and fish oil therapy. Sanger sequencing of the known T1HLP genes in this patient did not reveal any disease-causing mutations. Whole-exome sequencing revealed compound heterozygous rare variants (p.Val103Met and p.Arg540Gln) in the glucokinase regulator (GCKR) gene. CONCLUSIONS: GCKR encodes glucokinase regulatory protein, which is an inhibitor of glucokinase, an enzyme that drives glucose uptake in the liver. Loss of function GCKR variants, by enhancing glucose uptake in hepatocytes, may induce de novo lipogenesis and TG biosynthesis, resulting in extreme hypertriglyceridemia. We conclude that compound heterozygous rare variants in GCKR cause an extremely rare unique T1HLP, most likely by inducing excessive hepatic lipogenesis. PMID- 27403931 TI - Genetic and Clinical Predictive Factors of Sulfonylurea Failure in Patients with Type 2 Diabetes. AB - BACKGROUND: Sulfonylureas are widely used to treat type 2 diabetes (T2DM). Although genetic variations are associated with sulfonylurea treatment responses in T2DM patients, whether these variations can be used to predict heterogeneous treatment responses is unclear. In this study, we assessed the potential utility of combining information from multiple variants and phenotypes to predict sulfonylurea response. METHODS: Using data from the "Glibenclamide" arm (365 patients) of the Xiaoke Pill Trial that evaluated the safety and efficacy of sulfonylurea, we identified genetic variants associated with sulfonylurea treatment response, and we explored their ability to predict drug response when combined with phenotype information. RESULTS: The association of 780 single nucleotide polymorphisms (using Infinium HD iSelect chip) with drug efficacy was evaluated, and four genes identified with drug metabolism (FMO2, FMO3, UGT2B15, and CYP51A1, P < 0.05) were found to be associated with changes in HbA1c. In a clinical model, the baseline values of HbA1c and disposition index (DI) were significantly associated with HbA1c and fasting plasma glucose (FPG) target achievements. Compared with clinical models, the inclusion of genetic markers significantly increased the predictive ability for both HbA1c- and FPG-based outcomes. CONCLUSIONS: Our findings suggest that altered protein function in multiple pathways may cooperatively contribute to the increased discrimination by area under receiver operating curve for T2DM patients, and it may explain, in part, the relationship between inter-individual variability and the sulfonylurea response. PMID- 27403933 TI - First trimester combined screening - focus on early biochemistry. AB - First trimester combined screening (cFTS) for foetal trisomy 21 has become an established method in many countries. The screening is based on a combination of maternal-age-related risk, ultrasound (nuchal translucency) and two maternal serum biochemical markers, free beta human chorionic gonadotropin (FbhCG) and pregnancy associated plasma protein A (PAPP-A). The concentrations of these biochemical markers are affected by several maternal and pregnancy factors, which are discussed herein. Improvements in the algorithm have extended the screening to include trisomy 21 in mono- and dichorionic twin pregnancies, trisomy 18, trisomy 13 and triploidy. The results from large databases have shown that the screening algorithms are efficient for a range of rare autosomal trisomies and marker chromosomes and for a broad range of other chromosomal aberrations. Recent data show that the strength of the individual markers is highly dependent on the gestational age of sampling and indicate a general increase in the performance of the screening for trisomy 21 when using blood samples from early in the first trimester at gestational age 8-10 weeks. PMID- 27403934 TI - P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer. AB - Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC 9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. PMID- 27403935 TI - Heritable genome editing with CRISPR/Cas9 induces anosmia in a crop pest moth. AB - Lepidoptera suffer critical lack of genetic tools and heritable genome edition has been achieved only in a few model species. Here we demonstrate that the CRISPR/Cas9 system is highly efficient for genome editing in a non-model crop pest Lepidoptera, the noctuid moth Spodoptera littoralis. We knocked-out the olfactory receptor co-receptor Orco gene to investigate its function in Lepidoptera olfaction. We find that 89.6% of the injected individuals carried Orco mutations, 70% of which transmitted them to the next generation. CRISPR/Cas9 mediated Orco knockout caused defects in plant odor and sex pheromone olfactory detection in homozygous individuals. Our work genetically defines Orco as an essential OR partner for both host and mate detection in Lepidoptera, and demonstrates that CRISPR/Cas9 is a simple and highly efficient genome editing technique in noctuid pests opening new routes for gene function analysis and the development of novel pest control strategies. PMID- 27403936 TI - Fracture behaviors of ceramic tissue scaffolds for load bearing applications. AB - Healing large bone defects, especially in weight-bearing locations, remains a challenge using available synthetic ceramic scaffolds. Manufactured as a scaffold using 3D printing technology, Sr-HT-Gahnite at high porosity (66%) had demonstrated significantly improved compressive strength (53 +/- 9 MPa) and toughness. Nevertheless, the main concern of ceramic scaffolds in general remains to be their inherent brittleness and low fracture strength in load bearing applications. Therefore, it is crucial to establish a robust numerical framework for predicting fracture strengths of such scaffolds. Since crack initiation and propagation plays a critical role on the fracture strength of ceramic structures, we employed extended finite element method (XFEM) to predict fracture behaviors of Sr-HT-Gahnite scaffolds. The correlation between experimental and numerical results proved the superiority of XFEM for quantifying fracture strength of scaffolds over conventional FEM. In addition to computer aided design (CAD) based modeling analyses, XFEM was conducted on micro-computed tomography (MUCT) based models for fabricated scaffolds, which took into account the geometric variations induced by the fabrication process. Fracture strengths and crack paths predicted by the MUCT-based XFEM analyses correlated well with relevant experimental results. The study provided an effective means for the prediction of fracture strength of porous ceramic structures, thereby facilitating design optimization of scaffolds. PMID- 27403937 TI - The phase of ongoing EEG oscillations predicts the amplitude of peri-saccadic mislocalization. AB - Our constant eye movements mean that updating processes, such as saccadic remapping, are essential for the maintenance of a stable spatial representation of the world around us. It has been proposed that, rather than continually update a full spatiotopic map, only the location of a few key objects is updated, suggesting that the process is linked to attention. At the same time, mounting evidence links attention to oscillatory neuronal processes. We therefore hypothesized that updating processes should themselves show oscillatory characteristics, inherited from underlying attentional processes. To test this, we carried out a combined psychophysics and EEG experiment in human participants, using a saccadic mislocalization task as a behaviourally measureable proxy for spatial updating, and simultaneously recording 64-channel EEG. We then used a time-frequency analysis to test for a correlation between oscillation phase and perceptual outcome. We found a significant phase-dependence of mislocalization in a time-frequency region from around 400 ms prior to saccade initiation and peaking at around 7 Hz, principally apparent over occipital electrodes. Thus the degree of perceived mislocalization is correlated with the phase of a theta frequency oscillation prior to saccade onset. We conclude that spatial updating processes are indeed linked to rhythmic processes in the brain. PMID- 27403938 TI - How two-dimensional bending can extraordinarily stiffen thin sheets. AB - Curved thin sheets are ubiquitously found in nature and manmade structures from macro- to nanoscale. Within the framework of classical thin plate theory, the stiffness of thin sheets is independent of its bending state for small deflections. This assumption, however, goes against intuition. Simple experiments with a cantilever sheet made of paper show that the cantilever stiffness largely increases with small amounts of transversal curvature. We here demonstrate by using simple geometric arguments that thin sheets subject to two-dimensional bending necessarily develop internal stresses. The coupling between the internal stresses and the bending moments can increase the stiffness of the plate by several times. We develop a theory that describes the stiffness of curved thin sheets with simple equations in terms of the longitudinal and transversal curvatures. The theory predicts experimental results with a macroscopic cantilever sheet as well as numerical simulations by the finite element method. The results shed new light on plant and insect wing biomechanics and provide an easy route to engineer micro- and nanomechanical structures based on thin materials with extraordinary stiffness tunability. PMID- 27403939 TI - Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation. AB - Embryonic development is a multistep process involving activation and repression of many genes. Enhancer elements in the genome are known to contribute to tissue and cell-type specific regulation of gene expression during the cellular differentiation. Thus, their identification and further investigation is important in order to understand how cell fate is determined. Integration of gene expression data (e.g., microarray or RNA-seq) and results of chromatin immunoprecipitation (ChIP)-based genome-wide studies (ChIP-seq) allows large scale identification of these regulatory regions. However, functional validation of cell-type specific enhancers requires further in vitro and in vivo experimental procedures. Here we describe how active enhancers can be identified and validated experimentally. This protocol provides a step-by-step workflow that includes: 1) identification of regulatory regions by ChIP-seq data analysis, 2) cloning and experimental validation of putative regulatory potential of the identified genomic sequences in a reporter assay, and 3) determination of enhancer activity in vivo by measuring enhancer RNA transcript level. The presented protocol is detailed enough to help anyone to set up this workflow in the lab. Importantly, the protocol can be easily adapted to and used in any cellular model system. PMID- 27403941 TI - Reaction Mechanism of the Hydrogermylation/Hydrostannylation of Unactivated Alkenes with Two-Coordinate E(II) Hydrides (E=Ge, Sn): A Theoretical Study. AB - Quantum chemical calculations using density functional theory with the TPSS+D3(BJ) and M06-2X+D3(ABC) functionals have been carried out to understand the mechanisms of catalyst-free hydrogermylation/hydrostannylation reactions between the two-coordinate hydrido-tetrylenes :E(H)(L(+) ) (E=Ge or Sn, L(+) =N(Ar(+) )(SiiPr3 ); Ar(+) =C6 H2 {C(H)Ph2 }2 iPr-2,6,4) and a range of unactivated terminal (C2 H3 R, R=H, Ph, or tBu) and cyclic [(CH)2 (CH2 )2 (CH2 )n , n=1, 2, or 4] alkenes. The calculations suggest that the addition reactions of the germylenes and stannylenes to the cyclic and acyclic alkenes occur as one step processes through formal [2+2] addition of the E-H fragment across the C-C pi bond. The reactions have moderate barriers and are weakly exergonic. The steric bulk of the tetrylene amido groups has little influence on the activation barriers and on the reaction energies of the anti-Markovnikov pathway, but the Markovnikov addition is clearly disfavored by the size of the substituents. The addition of the tetrylenes to the cyclic alkenes is less exergonic than the addition to the terminal alkenes, which agrees with the experimentally observed reversibility of the former reactions. The hydrogermylation reactions have lower activation energies and are more exergonic than the stannylene addition. An energy decomposition analysis of the transition state for the hydrogermylation of cyclohexene shows that the reaction takes place with simultaneous formation of the Ge-C and (Ge)H-C' bonds. The dominant orbitals of the germylene are the sigma type lone pair MO of Ge, which serves as a donor orbital, and the vacant p(pi) MO of Ge, which acts as acceptor orbital for the pi* and pi MOs of the olefin. Inspection of the transition states of some selected reactions suggests that the differences between the activation energies come from a delicate balance between the deformation energies of the interacting species and their interaction energies. PMID- 27403942 TI - Robotic Technique for Accessing Left Hepatic Vein Through Ligamentum Venosum in Left Hepatectomy: How I Do It? AB - INTRODUCTION: Blood loss is associated with postoperative morbidity and mortality. Outflow control could be used concomitantly with inflow control for maximum reduction in blood loss during parenchymal transection. However, in left hepatectomy (LH) and left lateral sectionectomy (LLS), extrahepatic control of the left hepatic vein (LHV) is still less commonly used. Some authors reported extrahepatic LHV control technique using ligamentum venosum (LV) in open or laparoscopic surgery, but no reports of this technique in robotic surgery have been found. MATERIALS AND METHODS: The dissection of LV from the liver was performed, followed by clipping and transecting LV. The cephalad LV stump was retracted to the left inferior direction and then the dissection of the posterior part of LHV was performed until the opening space was connected to the anterior part of LHV. The LHV was encircled with the tape and vascular stapler was inserted to manage LHV stump. From 2013 to 2015, LHV was successfully encircled by using this technique in 7 out of 11 cases. The mean operative time was 244 minutes, the mean estimated blood loss was 300 mL, and the mean length of hospital stay was 4.8 days. Neither injury to LHV, nor complications related to the liver were found. DISCUSSION AND CONCLUSION: From our experiences, LHV was routinely controlled in robotic LH or LLS and the success rate was 60%. However, this technique is not recommended for the tumor that compresses or abuts LHV/LV, and in cirrhotic liver with associated hypertrophic left lateral segment. PMID- 27403940 TI - Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection. AB - Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines. PMID- 27403943 TI - Cycling and Diabetes Prevention: Practice-Based Evidence for Public Health Action. AB - Panter and Ogilvie describe findings that link recreational and commuter cycling with reduced incidence of diabetes. PMID- 27403944 TI - Circulating MicroRNA Quantification Using DNA-binding Dye Chemistry and Droplet Digital PCR. AB - Circulating (of cell-free) microRNAs (miRNAs) are released from cells into the blood stream. The amount of specific microRNAs in the circulation has been linked to a disease state and has the potential to be used as disease biomarker. A sensitive and accurate method for circulating microRNA quantification using a dye based chemistry and droplet digital PCR technology has been recently developed. Specifically, using Locked Nucleic Acid (LNA)-based miRNA-specific primers with a green fluorescent DNA-binding dye in a compatible droplet digital PCR system it is possible to obtain the absolute quantification of specific miRNAs. Here, we describe how performing this technique to assess miRNA amount in biological fluids, such as plasma and serum, is both feasible and effective. PMID- 27403945 TI - Physician Burnout: Let's Treat the Root Causes. PMID- 27403947 TI - How to Document and Code Medicare Preventive Services. PMID- 27403946 TI - Tackling Burnout in Employed Physicians. PMID- 27403948 TI - Home Care Gets a New Place in the Medical Neighborhood. PMID- 27403949 TI - Five Lessons for Working With a Scribe. PMID- 27403951 TI - Modifier 33. PMID- 27403950 TI - Employment Contracts for Family Physicians in an Evolving Market. PMID- 27403952 TI - ICD-10 coding for preventive visits. PMID- 27403953 TI - Ask about patients' future plans. PMID- 27403954 TI - Use color-coding to manage patient documents. PMID- 27403955 TI - Update deceased patients' records. PMID- 27403956 TI - Tips to Help Teen Patients Deal With Discrimination. PMID- 27403957 TI - Clinicopathological Characteristics, Surgery and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumors. AB - BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are a rare subset of GISTs (3-5%), and their clinicopathological features have not been fully described. The purpose of this retrospective study was to examine these characteristics and compare the operative procedures. METHODS: Twenty-five patients with duodenal GIST underwent complete resection, local resection (LR) or pancreaticoduodenectomy (PD) from 1990 to 2014 at our 2 hospitals. We analyzed patient characteristics, treatments, histological examinations, postoperative complications and survival outcomes. RESULTS: Twelve patients (48%) with no symptoms were incidentally diagnosed for unrelated reasons. Sixteen patients (64%) had c-kit mutations while 6 (24%) were wild-type, including 4 with a history of neurofibromatosis type 1. Comparing LR (n = 16) and PD (n = 9), the recurrence-free survival rate was significantly worse for PD. On multivariate analysis, however, tumor size was an independent and significant prognostic factor, but not operative procedure. There was no body weight change with LR, but body weight decreased by 7% with PD. CONCLUSION: Duodenal GISTs had different characteristic genetic mutations compared to other GISTs. LR for duodenal GISTs appears to be oncologically and nutritionally feasible. PMID- 27403958 TI - Accelerometer-Measured Physical Activity and Sedentary Time Differ According to Education Level in Young Adults. AB - This study examined the association of education level with objectively measured physical activity and sedentary time in young adults. Data from the Finnish ESTER study (2009-2011) (n = 538) was used to examine the association between educational attainment and different subcomponents of physical activity and sedentary time measured using hip-worn accelerometers (ActiGraph GT1M) for seven consecutive days. Overall physical activity, moderate-to-vigorous physical activity (MVPA), light-intensity physical activity and sedentary time were calculated separately for weekdays and weekend days. A latent profile analysis was conducted to identify the different profiles of sedentary time and the subcomponents of physical activity. The educational differences in accelerometer measured physical activity and sedentary time varied according to the subcomponents of physical activity, and between weekdays and weekend days. A high education level was associated with high MVPA during weekdays and weekend days in both sexes, high sedentary time during weekdays in both sexes, and a low amount of light-intensity physical activity during weekdays in males and during weekdays and weekend days in females. The results indicate different challenges related to unhealthy behaviours in young adults with low and high education: low education is associated with a lack of MVPA, whereas high education is associated with a lack of light-intensity physical activity and high sedentary time especially during weekdays. PMID- 27403959 TI - Conjugation of Methotrexate-Amino Derivatives to Macromolecules through Carboxylate Moieties Is Superior Over Conventional Linkage to Amino Residues: Chemical, Cell-Free and In Vitro Characterizations. AB - In this study, we examined the possibility of introducing methotrexate (MTX) to the carboxylate rather than to the epsilon-amino side chains of proteins. We found that MTX-amino compounds covalently linked to the carboxylate moieties of macromolecules, undergo unusual peptide-bond cleavage, with the release of the MTX amino derivatives from the conjugates. This event takes place at an accelerated rate under acidic conditions, and at a slower rate at physiological pH values. The glutamate portion of MTX is responsible for this behavior, with little or no contribution of the p-aminobenzoate-pteridine ring that is linked to the alpha-amino side chain of the glutamate. Carboxylate-linked Fmoc-Glu-gamma CONH-(CH2)6-NH2 undergoes hydrolysis in a nearly indistinguishable fashion. A free alpha carboxylate moiety is essential for this effect. Carboxylate linked Fmoc-glutamic-amide-gamma-CONH-(CH2)6-NH2 undergoes no hydrolysis under acidic conditions. Based on these findings, we engineered a cysteine specific MTX containing reagent. Its linkage to bovine serum albumin (BSA) yielded a conjugate with profound antiproliferative efficacy in a MTX-sensitive glioma cell line. In conclusion, carboxylate linked MTX-amino derivatives in particular, and carboxylate linked R-alpha-GLU-gamma amino compounds in general are equipped with'built-in chemical machinery' that releases them under mild acidic conditions. PMID- 27403960 TI - (54)Mn Radiotracers Demonstrate Continuous Dissolution and Reprecipitation of Vernadite (delta-MnO2) during Interaction with Aqueous Mn(II). AB - (54)Mn radiotracers were used to assess Mn atom exchange between aqueous Mn(II) and vernadite (delta-MnO2) at pH 5.0. Continuous solid-liquid redistribution of (54)Mn atoms occurred, and systems are near isotopic equilibrium after reaction for 3 months. Despite this extensive exchange, X-ray diffraction and X-ray absorption spectroscopy data showed no major changes in vernadite bulk mineralogy. These results demonstrate that the vernadite-Mn(II) interface is dynamic, with the substrate undergoing continuous dissolution and reprecipitation mediated by aqueous Mn(II) without observable impacts on its mineralogy. Interfacial redox reactions between adsorbed Mn(II) and solid-phase Mn(IV) and Mn(III) are proposed as the main drivers of this process. Interaction between aqueous Mn(II) and structural Mn(III) likely involves interfacial electron transfer coupled with Mn atom exchange. The exchange of aqueous Mn(II) and solid phase Mn(IV) is more complex and is proposed to result from coupled interfacial comproportionation-disproportionation reactions, where electron transfer from adsorbed Mn(II) to lattice Mn(IV) produces transient Mn(III) species that disproportionate to regenerate aqueous Mn(II) and structural Mn(IV). These findings provide further evidence of the importance of Mn(II)(aq)-MnO2(s) interactions and the attendant production of transient Mn(III) intermediates to the geochemical functioning of phyllomanganates in environments undergoing Mn redox cycling. PMID- 27403961 TI - AplusB: A Web Application for Investigating A + B Designs for Phase I Cancer Clinical Trials. AB - In phase I cancer clinical trials, the maximum tolerated dose of a new drug is often found by a dose-escalation method known as the A + B design. We have developed an interactive web application, AplusB, which computes and returns exact operating characteristics of A + B trial designs. The application has a graphical user interface (GUI), requires no programming knowledge and is free to access and use on any device that can open an internet browser. A customised report is available for download for each design that contains tabulated operating characteristics and informative plots, which can then be compared with other dose-escalation methods. We present a step-by-step guide on how to use this application and provide several illustrative examples of its capabilities. PMID- 27403962 TI - Effect of BET Missense Mutations on Bromodomain Function, Inhibitor Binding and Stability. AB - Lysine acetylation is an important epigenetic mark regulating gene transcription and chromatin structure. Acetylated lysine residues are specifically recognized by bromodomains, small protein interaction modules that read these modification in a sequence and acetylation dependent way regulating the recruitment of transcriptional regulators and chromatin remodelling enzymes to acetylated sites in chromatin. Recent studies revealed that bromodomains are highly druggable protein interaction domains resulting in the development of a large number of bromodomain inhibitors. BET bromodomain inhibitors received a lot of attention in the oncology field resulting in the rapid translation of early BET bromodomain inhibitors into clinical studies. Here we investigated the effects of mutations present as polymorphism or found in cancer on BET bromodomain function and stability and the influence of these mutants on inhibitor binding. We found that most BET missense mutations localize to peripheral residues in the two terminal helices. Crystal structures showed that the three dimensional structure is not compromised by these mutations but mutations located in close proximity to the acetyl-lysine binding site modulate acetyl-lysine and inhibitor binding. Most mutations affect significantly protein stability and tertiary structure in solution, suggesting new interactions and an alternative network of protein protein interconnection as a consequence of single amino acid substitution. To our knowledge this is the first report studying the effect of mutations on bromodomain function and inhibitor binding. PMID- 27403963 TI - Methods for Acute and Subacute Murine Hindlimb Ischemia. AB - Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality in developed countries, and animal models that reliably reproduce the human disease are necessary to develop new therapies for this disease. The mouse hindlimb ischemia model has been widely used for this purpose, but the standard practice of inducing acute limb ischemia by ligation of the femoral artery can result in substantial tissue necrosis, compromising investigators' ability to study the vascular and skeletal muscle tissue responses to ischemia. An alternative approach to femoral artery ligation is the induction of gradual femoral artery occlusion through the use of ameroid constrictors. When placed around the femoral artery in the same or different locations as the sites of femoral artery ligation, these devices occlude the artery over 1 - 3 days, resulting in more gradual, subacute ischemia. This results in less substantial skeletal muscle tissue necrosis, which may more closely mimic the responses seen in human PAD. Because genetic background influences outcomes in both the acute and subacute ischemia models, consideration of the mouse strain being studied is important in choosing the best model. This paper describes the proper procedure and anatomical placement of ligatures or ameroid constrictors on the mouse femoral artery to induce subacute or acute hindlimb ischemia in the mouse. PMID- 27403964 TI - Unraveling the Fundamental Mechanisms of Solvent-Additive-Induced Optimization of Power Conversion Efficiencies in Organic Photovoltaic Devices. AB - The realization of controllable morphologies of bulk heterojunctions (BHJ) in organic photovoltaics (OPVs) is one of the key factors enabling high-efficiency devices. We provide new insights into the fundamental mechanisms essential for the optimization of power conversion efficiencies (PCEs) with additive processing to PBDTTT-CF:PC71BM system. We have studied the underlying mechanisms by monitoring the 3D nanostructural modifications in BHJs and correlated the modifications with the optical analysis and theoretical modeling of charge transport. Our results demonstrate profound effects of diiodooctane (DIO) on morphology and charge transport in the active layers. For small amounts of DIO (<3 vol %), DIO promotes the formation of a well-mixed donor-acceptor compact film and augments charge transfer and PCE. In contrast, for large amounts of DIO (>3 vol %), DIO facilitates a loosely packed mixed morphology with large clusters of PC71BM, leading to deterioration in PCE. Theoretical modeling of charge transport reveals that DIO increases the mobility of electrons and holes (the charge carriers) by affecting the energetic disorder and electric field dependence of the mobility. Our findings show the implications of phase separation and carrier transport pathways to achieve optimal device performances. PMID- 27403965 TI - Inhibition of precancerous lesions development in kidneys by chrysin via regulating hyperproliferation, inflammation and apoptosis at pre clinical stage. AB - Chrysin (CH) is natural, biologically active compound, belongs to flavoniod family and possesses diverse pharmacological activities as anti-inflammatory, anti-oxidant and anti-cancer. It is found in many plants, honey and propolis. In the present study, we investigated the chemopreventive efficacy of CH against N nitrosodiethylamine (DEN) initiated and Fe-NTA induced precancerous lesions and its role in regulating oxidative injury, hyperproliferation, tumor incidences, histopathological alterations, inflammation, and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200 mg/kg bw) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated Fe-NTA enhanced renal lipid peroxidation, serum toxicity markers and restored renal anti oxidant armory significantly. CH supplementation suppressed the development of precancerous lesions via down regulation of cell proliferation marker like PCNA; inflammatory mediators like TNF-alpha, IL-6, NFkB, COX-2, iNOS; tumor incidences. CH up regulated intrinsic apoptotic pathway proteins like bax, caspase-9 and caspase-3 along with down regulation of Bcl-2 triggering apoptosis. Histopathological and ultra structural alterations further confirmed biochemical and immunohistochemical results. These results provide powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways. PMID- 27403966 TI - Asian Targeted Temperature Management Task Panel Report. AB - In the fields of emergency and critical care, targeted temperature management has become a critical issue and particularly popular in clinical practices throughout Asia. As more research is carried out, evidence and concepts about targeted temperature management continue to evolve. Areas of interest include new 2015 resuscitation guidelines, temperature management in pediatrics, and integrated care and neurological monitoring for cardiac arrest patients. The Asian Targeted Temperature Management task panel includes colleagues from various Asian countries and allows them to exchange experiences in a professional environment. Some of the key issues include optimal therapeutic hypothermia temperature for postcardiac arrest syndrome pursuant to 2015 guidelines, an integral approach to postcardiac arrest syndrome with hemodynamic monitoring and stabilization, roles of percutaneous coronary intervention and extracorporeal membrane oxygenation, and temperature management for neonatal hypoxic-ischemic encephalopathy. Panel experts reviewed all of the aforementioned issues and discussed the feasibility and effectiveness of targeted temperature management based on the Asian population. These discussions can expand the perspectives with regard to applying targeted temperature management all over the world. PMID- 27403968 TI - Scanning sports. PMID- 27403967 TI - Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand Gated Ion Channels. AB - Ion channel gating is a stimulus-driven orchestration of protein motions that leads to transitions between closed, open, and desensitized states. Fundamental to these transitions is the intrinsic flexibility of the protein, which is critically modulated by membrane lipid-composition. To better understand the structural basis of channel function, it is necessary to study protein dynamics in a physiological membrane environment. Electron Paramagnetic Resonance (EPR) spectroscopy is an important tool to characterize conformational transitions between functional states. In comparison to NMR and X-ray crystallography, the information obtained from EPR is intrinsically of lower resolution. However, unlike in other techniques, in EPR there is no upper-limit to the molecular weight of the protein, the sample requirements are significantly lower, and more importantly the protein is not constrained by the crystal lattice forces. Therefore, EPR is uniquely suited for studying large protein complexes and proteins in reconstituted systems. In this article, we will discuss general protocols for site-directed spin labeling and membrane reconstitution using a prokaryotic proton-gated pentameric Ligand-Gated Ion Channel (pLGIC) from Gloeobacter violaceus (GLIC) as an example. A combination of steady-state Continuous Wave (CW) and Pulsed (Double Electron Electron Resonance-DEER) EPR approaches will be described that will enable a complete quantitative characterization of channel dynamics. PMID- 27403971 TI - Water: The Most Refreshing Drink. PMID- 27403970 TI - Noteworthy. PMID- 27403972 TI - Establishing the ldentity of Sports Medicine Physicians. PMID- 27403974 TI - How We Manage Plantar Fasciitis. AB - In brief: Plantar fasciitis is a prolonged overuse injury that is potentially incapacitating and causes heel or arch pain. It is common among runners and athletes who participate in jumping sports such as basketball. The onset of pain is insidious, and an athlete may tolerate it for weeks before seeking medical advice. Although few runners can remember a particular moment or event when pain began, plantar fasciitis usually occurs after sudden increases in mileage, frequency of running, or running speed. Combined therapy, including relative rest, Achilles tendon stretching, medication, and heel cups, alleviates the pain in most athletes. PMID- 27403975 TI - Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids. AB - In brief: Serum total cholesterol (TC) concentrations were measured in three groups of male power lifters who used anabolic-androgenic steroids: 19 who used steroids for eight weeks, seven of the 19 who continued steroid use for three years, and three who had been using steroids for eight years. Mean TC levels increased, and after steroid use ended, they decreased promptly to near presteroid levels. High-density lipoprotein cholesterol and serum triglyceride levels indicated that the TC increase occurred in the low-density lipoprotein fraction. Presteroid TC concentration is not predictive of the magnitude of steroid-induced hypercholesterolemia, nor does a low presteroid TC level necessarily protect against this abnormality. PMID- 27403976 TI - Percutaneous Automated Diskectomy in Athletes. AB - In brief: Six athletes underwent percutaneous automated diskectomy-a new technique for aspirating lumbar disks. The patients had herniated lumbar disks (confirmed by computed tomography and magnetic resonance imaging scans, and/or myelography). Conservative therapy had failed, and they were unable to participate in their respective sports. The procedure, which requires local anesthesia and takes about 45 minutes, was successful in all six cases. No serious complications resulted, and the athletes returned to their sport and functioned normally within six months. Thus, percutaneous automated diskectomy seems to be a reasonable treatment alternative for athletes with herniated lumbar disks without fragmentation into the spinal canal. PMID- 27403977 TI - Sports Medicine Education for Rural Practice. AB - In brief: Teaching sports medicine to family practice residents as a formal clinical rotation is relatively new. However, there has been considerable activity in this important area. Educational objectives for family practice residents have been well defined. Less well defined are the community and institutional resources and relationships necessary for a successful resident program in sports medicine. The authors discuss the effective sports medicine rotation in the Family Practice Residency Program at Marshall University School of Medicine in Huntington, West Virginia. PMID- 27403978 TI - Magnetic Resonance Imaging for Meniscal Tears of the Knee. AB - In brief: Magnetic resonance imaging (MRI). has become a standard diagnostic technique in many medical facilities for evaluating the menisci of the knee. MRI provides superior soft-tissue contrast with high resolution and takes little time (typically less than 30 minutes). It does not require intra-articular contrast media and is not limited to surface abnormalities, as are arthrography and arthroscopy. Unlike MRI, both arthrography and arthroscopy cause disturbances to the external capsule of the knee, with associated patient discomfort and limited physical activity for some time following the procedure. The author discusses the advantages of MRI and presents a case report in which it was used to make the diagnosis and determine the appropriate treatment modality. PMID- 27403979 TI - High-Altitude Pulmonary Edema: The Disguised Killer. AB - In brief: High-altitude pulmonary edema afflicts 1% to 2% of sojourners above 10,000 to 11,000 ft. It is at the severe end of a spectrum of high-altitude illnesses; symptoms can be subtle or overt and can rapidly progress to coma and death. The best prevention is acclimatization-slow, gradual ascent that allows the body to adapt to a hypoxic environment. The author reviews the signs and symptoms and how to recognize them, the pathophysiology, and the prevention and management of this avoidable, but potentially fatal, condition. PMID- 27403980 TI - Effects of Cold and Compression on Edema. AB - In brief: A 40-minute cooling period was used to treat artificially induced acute inflammatory reactions in human tissue. Results showed no significant change in the volume of the inflammatory reaction at one hour, though a transient attenuation during the first 15 minutes was detected. The addition of mild pressure (10 mm Hg) to mild cooling (range, 15 degrees to 25 degrees C) produced a highly significant reduction in swelling from 15 minutes onward, This effect was sustained as long as swelling was detectable. Pressure alone (20 mm Hg) had a nonsignificant effect. The authors compare two cooling devices, an inflatable cooling cuff and an evaporative bandage, which were both found to be effective. The authors suggest that these devices could be used more routinely in emergency medicine. PMID- 27403981 TI - Preventing Eye Injuries in Sports: Some Questions and Answers. AB - In brief: The frequency of eye injuries in sports raises numerous questions about preventive eye care for athletes: What style of frame and type of lens material provide the best protection for athletes, especially those who play racket sports? Are polycarbonate lenses available in sunglasses? What is polycarbonate? What standards are used to ensure that an eye protector is safe and effective? Should the government intervene by mandating the use of protective eye wear for certain sports? The author addresses these and other issues. PMID- 27403982 TI - Rotator Cuff Damage: Reexamining the Causes and Treatments. AB - Rotator cuff problems plague many recreational and professional athletes. Now some physicians are questioning the role of primary impingement in a deficient or torn cuff, while trying new surgical procedures as alternatives to the traditional open acromioplasty. PMID- 27403983 TI - Scottish Golf: Pilgrims in Plus Fours. AB - Scotland-where golf was invented-is a veritable treasure trove for dedicated golfers. However, the country's 19th-hole attractions-restaurants and pubs, castles and gardens, beaches and lochs-should not be overlooked. PMID- 27403984 TI - Keeping Pace With the Many Forms of Walking. AB - Walking is perhaps the most g basic form of exercise, yet the recent walking boom has produced many new styles-and names-for it. Is walking the same by any name? What are the merits of these different forms? PMID- 27403986 TI - Coming in sportsmedicine. PMID- 27403988 TI - Sportsmedicine forum. PMID- 27403989 TI - Strength and Endurance of the Shoulder Muscles. PMID- 27403991 TI - Functional Three-Dimensional Graphene/Polymer Composites. AB - Integration of graphene with polymers to construct three-dimensional porous graphene/polymer composites (3DGPCs) has attracted considerable attention in the past few years for both fundamental studies and diverse technological applications. With the broad diversity in molecular structures of graphene and polymers via rich chemical routes, a number of 3DGPCs have been developed with unique structural, electrical, and mechanical properties, chemical tenability, and attractive functions, which greatly expands the research horizon of graphene based composites. In particular, the properties and functions of the 3DGPCs can be readily tuned by precisely controlling the hierarchical porosity in the 3D graphene architecture as well as the intricate synergistic interactions between graphene and polymers. In this paper, we review the recent progress in 3DGPCs, including their synthetic strategies and potential applications in environmental protection, energy storage, sensors, and conducting composites. Lastly, we will conclude with a brief perspective on the challenges and future opportunities. PMID- 27403992 TI - An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals. AB - Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID- 27403993 TI - Chronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway. AB - The pathogenesis of alcoholic liver disease (ALD) is not well established. However, oxidative stress and associated decreases in levels of glutathione (GSH) are known to play a central role in ALD. The present study examines the effect of GSH deficiency on alcohol-induced liver steatosis in Gclm knockout (KO) mice that constitutively have ~15% normal hepatic levels of GSH. Following chronic (6 week) feeding with an ethanol-containing liquid diet, the Gclm KO mice were unexpectedly found to be protected against steatosis despite showing increased oxidative stress (as reflected in elevated levels of CYP2E1 and protein carbonyls). Gclm KO mice also exhibit constitutive activation of liver AMP activated protein kinase (AMPK) pathway and nuclear factor-erythroid 2-related factor 2 target genes, and show enhanced ethanol clearance, altered hepatic lipid profiles in favor of increased levels of polyunsaturated fatty acids and concordant changes in expression of genes associated with lipogenesis and fatty acid oxidation. In summary, our data implicate a novel mechanism protecting against liver steatosis via an oxidative stress adaptive response that activates the AMPK pathway. We propose redox activation of the AMPK may represent a new therapeutic strategy for preventing ALD. PMID- 27403994 TI - The Photosensitivity of Rhodopsin Bleaching and Light-Induced Increases of Fundus Reflectance in Mice Measured In Vivo With Scanning Laser Ophthalmoscopy. AB - PURPOSE: To quantify bleaching-induced changes in fundus reflectance in the mouse retina. METHODS: Light reflected from the fundus of albino (Balb/c) and pigmented (C57Bl/6J) mice was measured with a multichannel scanning laser ophthalmoscopy optical coherence tomography (SLO-OCT) optical system. Serial scanning of small retinal regions was used for bleaching rhodopsin and measuring reflectance changes. RESULTS: Serial scanning generated a saturating reflectance increase centered at 501 nm with a photosensitivity of 1.4 * 10-8 per molecule MUm2 in both strains, 2-fold higher than expected were irradiance at the rod outer segment base equal to that at the retinal surface. The action spectrum of the reflectance increase corresponds to the absorption spectrum of mouse rhodopsin in situ. Spectra obtained before and after bleaching were fitted with a model of fundus reflectance, quantifying contributions from loss of rhodopsin absorption with bleaching, absorption by oxygenated hemoglobin (HbO2) in the choroid (Balb/c), and absorption by melanin (C57Bl/6J). Both mouse strains exhibited light-induced broadband reflectance changes explained as bleaching-induced reflectivity increases at photoreceptor inner segment/outer segment (IS/OS) junctions and OS tips. CONCLUSIONS: The elevated photosensitivity of rhodopsin bleaching in vivo is explained by waveguide condensing of light in propagation from rod inner segment (RIS) to rod outer segment (ROS). The similar photosensitivity of rhodopsin in the two strains reveals that little light backscattered from the sclera can enter the ROS. The bleaching-induced increases in reflectance at the IS/OS junctions and OS tips resemble results previously reported in human cones, but are ascribed to rods due to their 30/1 predominance over cones in mice and to the relatively minor amount of cone M-opsin in the regions scanned. PMID- 27403995 TI - Nox4 Plays a Role in TGF-beta-Dependent Lens Epithelial to Mesenchymal Transition. AB - PURPOSE: Transforming growth factor-beta induces an epithelial to mesenchymal transition (EMT) in the lens, presented as an aberrant growth and differentiation of lens epithelial cells. Studies in other models of EMT have shown that TGF-beta driven EMT is dependent on the expression of the reactive oxygen species (ROS) producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase-4 (Nox4). We investigate the role of this enzyme in TGF-beta-induced lens EMT and determine whether it is required for this pathologic process. METHODS: Rat lens epithelial explants were used to investigate the role of Nox4 in TGF-beta-driven lens EMT. Nox1-4 expression and localization was determined by immunolabeling and/or RT-PCR. NADPH-oxidase-produced ROS were visualized microscopically using the fluorescent probe, dihydroethidium (DHE). VAS2870, a pan-NADPH oxidase inhibitor, was used to determine the specificity of Nox4 expression and its role in ROS production, and subsequently TGF-beta-driven EMT. RESULTS: We demonstrate, for the first time to our knowledge, in rat lens epithelial explants that TGF beta treatment induces Nox4 (but not Nox1-3) expression and activity. Increased Nox4 expression was first detected at 6 to 8 hours following TGF-beta treatment and was maintained in explants up to 48 hours. At 8 hours after TGF-beta treatment, Nox4 was observed in cell nuclei, while at later stages in the EMT process (at 48 hours), Nox4 was predominately colocalized with alpha-smooth muscle actin. The inhibition of Nox4 expression and activity using VAS2870 inhibited EMT progression. CONCLUSIONS: Transforming growth factor-beta drives the expression of the ROS-producing enzyme Nox4 in rat lens epithelial cells and Nox4 inhibition can impede the EMT process. PMID- 27403996 TI - Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia. AB - PURPOSE: To evaluate the relationships between RPE, photoreceptor, and choroidal degeneration in choroideremia. METHODS: Enhanced-depth imaging optical coherence tomography (EDI-OCT), scanning laser ophthalmoscopy (SLO), and autofluorescence (AF) were performed on 39 patients (78 eyes) with choroideremia. The edges of surviving outer retina on OCT and residual AF were aligned. The distribution of outer retinal tubulations was mapped over a range of ages (16-71 years), and comparison made between pre- and postsubretinal gene therapy. Subfoveal choroidal thickness (SFCT) was compared between 23 choroideremia patients (42 eyes) and 20 age- and refraction-matched male controls (40 eyes). RESULTS: The edges of RPE AF aligned with a reduction in outer nuclear layer thickness (Spearman's rho = 0.9992). Correlation was also found between the quality of AF and integrity of ellipsoid zone within islands of surviving retina. Tubulations existed in 71 of 78 (91%) eyes with choroideremia and remained stable following gene therapy. Subfoveal choroidal thickness was reduced at baseline in choroideremia (179.7 +/- 17.2 MUm) compared with controls (302.0 +/- 4.8 MUm; P < 0.0001), but did not undergo significant thinning until end-stage retinal degeneration (43.1 +/- 6.5 MUm). CONCLUSIONS: The data suggest that RPE loss is the primary cause of photoreceptor degeneration in choroideremia. The choroid is thinner than controls from early stages, in keeping with a mild developmental defect. Photoreceptors appear to lose outer segments following loss of underlying RPE and form tubulations at the edges of degeneration. The preservation of tubulations over time and after subretinal injection would be consistent with these structures maintaining attachment to the inner retina and hence being potentially light responsive (ClinicalTrials.gov, NCT01461213). PMID- 27403998 TI - HDAC Inhibitor-Mediated Epigenetic Regulation of Glaucoma-Associated TGFbeta2 in the Trabecular Meshwork. AB - PURPOSE: Elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG) results from glaucomatous damage to the trabecular meshwork (TM). The glaucoma-associated factor TGFbeta2 is increased in aqueous humor and TM of POAG patients. We hypothesize that histone acetylation has a role in dysregulated TGFbeta2 expression. METHODS: Protein acetylation was compared between nonglaucomatous TM (NTM) and glaucomatous TM (GTM) cells using Western immunoblotting (WB). Nonglaucomatous TM cells were treated with 10 nM thailandepsin-A (TDP-A), a potent histone deacetylase inhibitor for 4 days. Total and nuclear proteins, RNA, and nuclear protein-DNA complexes were harvested for WB, quantitative PCR (qPCR), and chromatin immunoprecipitation (ChIP) assays, respectively. Paired bovine eyes were perfused with TDP-A versus DMSO, or TDP-A versus TDP-A plus the TGFbeta pathway inhibitor LY364947 for 5 to 9 days. Intraocular pressure, TM, and perfusate proteins were compared. RESULTS: We found increased acetylated histone 3 and total protein acetylation in the GTM cells and TDP-A treated NTM cells. Chromatin immunoprecipitation assays showed that TDP-A induced histone hyperacetylation associated with the TGFbeta2 promoter. This change of acetylation significantly increased TGFbeta2 mRNA and protein expression in NTM cells. In perfusion-cultured bovine eyes, TDP-A increased TGFbeta2 in the perfusate as well as elevated IOP. Histologic and immunofluorescent analyses showed increased extracellular matrix and cytoskeletal proteins in the TM of TDP-A treated bovine eyes. Cotreatment with the TGFbeta pathway inhibitor LY364947 blocked TDP-A-induced ocular hypertension. CONCLUSIONS: Our results suggest that histone acetylation has an important role in increased expression of the glaucoma-associated factor TGFbeta2. Histone hyperacetylation may be the initiator of glaucomatous damage to the TM. PMID- 27403997 TI - Modeling Keratoconus Using Induced Pluripotent Stem Cells. AB - PURPOSE: To model keratoconus (KC) using induced pluripotent stem cells (iPSC) generated from fibroblasts of both KC and normal human corneal stroma by a viral method. METHODS: Both normal and KC corneal fibroblasts from four human donors were reprogramed directly by delivering reprogramming factors in a single virus using 2A "self-cleaving" peptides, using a single polycistronic lentiviral vector coexpressing four transcription factors (Oct 4, Sox2, Klf4, and Myc) to yield iPSC. These iPS cells were characterized by immunofluorescence detection using of stem cell markers (SSEA4, Oct4, and Sox2). The mRNA sequencing was performed and the datasets were analyzed using ingenuity pathways analysis (IPA) software. RESULTS: The generated stem cell-like clones expressed the pluripotency markers, SSEA4, Oct4, Sox2, Tra-1-60, and also expressed pax6. Our transcriptome analysis showed 4300 genes, which had 2-fold change and 870 genes with a q-value of <0.05 in keratoconus iPSC compared to normal iPSC. One of the genes that showed difference in KC iPSC was FGFR2 (down-regulated by 2.4 fold), an upstream target of Pi3-Kinase pathway, was further validated in keratoconus corneal sections and also KC iPSC-derived keratocytes (down regulated by 2.0-fold). Both normal and KC derived keratocytes expressed keratocan, signature marker for keratocytes. KC iPSC-derived keratocytes showed adverse growth and proliferation and was further confirmed by using Ly2924002, a PI3k inhibitor, which severely affected the growth and differentiation in normal iPSC. CONCLUSIONS: Based on our result, we propose a model for KC in which inhibition FGFR2-Pi3-Kinase pathway affects the AKT phosphorylation, and thus affecting the keratocytes survival signals. This inhibition of the survival signals could be a potential mechanism for the KC specific decreased cell survival and apoptosis of keratocytes. PMID- 27403999 TI - Design of Core-Shell Heterostructure Nanofibers with Different Work Function and Their Sensing Properties to Trimethylamine. AB - The metal oxide semiconductor (MOS) core-shell heterostructure nanofibers (NFs) have been successfully synthesized via an environmentally friendly coaxial electrospinning approach. To demonstrate the potential applications of the as prepared samples, sensors based on MOS core-shell heterostructure NFs have been fabricated and their gas sensing properties were investigated. Results show that the sensors exhibit an advanced gas sensing property to trimethylamine (TMA) including the outstanding selectivity and rapid response/recovery processes in comparison with the sensors based on single MOS NFs. These phenomena are closely associated with the electron flow caused by the work function difference between MOS of the core and the shell. The approach proposed in this study may contribute to the realization of more sensitive MOS core-shell heterostructure sensors. PMID- 27404000 TI - From Constructs to Crystals - Towards Structure Determination of beta-barrel Outer Membrane Proteins. AB - Membrane proteins serve important functions in cells such as nutrient transport, motility, signaling, survival and virulence, yet constitute only ~1% percent of known structures. There are two types of membrane proteins, alpha-helical and beta-barrel. While alpha-helical membrane proteins can be found in nearly all cellular membranes, beta-barrel membrane proteins can only be found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. One common bottleneck in structural studies of membrane proteins in general is getting enough pure sample for analysis. In hopes of assisting those interested in solving the structure of their favorite beta-barrel outer membrane protein (OMP), general protocols are presented for the production of target beta-barrel OMPs at levels useful for structure determination by either X-ray crystallography and/or NMR spectroscopy. Here, we outline construct design for both native expression and for expression into inclusion bodies, purification using an affinity tag, and crystallization using detergent screening, bicelle, and lipidic cubic phase techniques. These protocols have been tested and found to work for most OMPs from Gram-negative bacteria; however, there are some targets, particularly for mitochondria and chloroplasts that may require other methods for expression and purification. As such, the methods here should be applicable for most projects that involve OMPs from Gram-negative bacteria, yet the expression levels and amount of purified sample will vary depending on the target OMP. PMID- 27404001 TI - Dental students' experiences of treating orthodontic emergencies - a qualitative assessment of student reflections. AB - INTRODUCTION: Professional regulatory bodies in the UK and Europe state that dental graduates should be able to manage orthodontic emergency patients. Therefore, the aim of this study was to explore dental student experiences of treating orthodontic emergencies within a teaching institution. MATERIALS AND METHOD: This study was designed as a single-centre evaluation of teaching based in a UK university orthodontic department. The participants were fourth-year dental students who treated orthodontic emergency patients under clinical supervision as part of the undergraduate curriculum. Student logbook entries for one academic year detailing the types of emergencies treated and structured, reflective commentaries for each procedure were analysed using thematic analysis methods. The total numbers and types of orthodontic emergencies treated by students were presented. Overall, self-reported student confidence in managing orthodontic emergencies was calculated. Themes, which represented student reflections, were identified. RESULTS: Seventy-two students participated in the study. Overall, 69% of students stated they were confident in managing orthodontic emergencies. Students treated a range of emergencies, of which the most frequent was debonded brackets (38%). Reflections from student commentaries were housed under a primary theme of building procedural confidence. Three subthemes were identified: (i) theory-practice integration; (ii) expanding clinical experience; and (iii) importance of a supportive clinical learning environment. CONCLUSION: The majority of dental students were confident in managing orthodontic emergencies. Theoretical knowledge supplemented by exposure to a range of clinical problems within a supported learning environment made students feel more confident. PMID- 27404002 TI - Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area. AB - Increasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5- < 10 mg/day aOR = 2.51, Ptrend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors. PMID- 27404004 TI - Collateral circulation in pediatric post-thrombotic syndrome. PMID- 27404003 TI - Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system. AB - Nervous system development is a process that integrates cell proliferation, differentiation, and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic, and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerged while integrating this information. PMID- 27404005 TI - High-throughput proteome dynamics for discovery of key proteins in sentinel species: Unsuspected vitellogenins diversity in the crustacean Gammarus fossarum. AB - In environmental science, omics-based approaches are widely used for the identification of gene products related to stress response. However, when dealing with non-model species, functional prediction of genes is challenging. Indeed, functional predictions are often obtained by sequence similarity searches and functional data from phylogenetically distant organisms, which can lead to inaccurate predictions due to quite different evolutionary scenarios. In oviparous females, vitellogenin production is vital for embryonic development, ensuring population viability. Its abnormal presence in fish male organisms is commonly employed as a biomarker of exposure to xenoestrogens, named endocrine disruptors. Here, in the freshwater amphipod Gammarus fossarum, we identified vitellogenin proteins by means of a proteome temporal dynamics analysis during oogenesis and embryogenesis. This exhaustive approach allows several functional molecular hypotheses in the oogenesis process to be drawn. Moreover, we revealed an unsuspected diversity of molecular players involved in yolk formation as eight proteins originating from different families of the large lipid transfer protein superfamily were identified as "true vitellogenins". BIOLOGICAL SIGNIFICANCE: In non-model species, next generation sequencing technologies development enables quickly deciphering gene and protein sequences but accuracy of associated functional prediction remains to be established. Here, in the crustacean Gammarus fossarum, a key sentinel species in freshwater biomonitoring, we identified key molecular players involved in the female reproduction by studying the proteome dynamics of ovaries and embryos. An unsuspected diversity of vitellogenin proteins was evidenced. These proteins being vital for offspring development, their high diversity may be advantageous for the organism's reproduction. Phylogenetic analysis showed that some forms are true vitellogenin orthologs while others are included in the apolipoprotein family, a paralogous group from the vitellogenin family. Among crustaceans, Gammarus fossarum is the first documented case where diverse protein families are involved in the yolk formation process. PMID- 27404006 TI - Feasibility and Effectiveness of a Peer Referral Incentive Intervention to Promote Male Circumcision Uptake in Zambia. AB - BACKGROUND: Medical male circumcision is a promising HIV prevention tool in countries with generalized HIV epidemics, but demand creation interventions are needed to support scale-up. We piloted a peer referral intervention in which circumcision clients were offered incentives for referring their peers for circumcision. METHODS: The intervention was implemented between June 2014 and February 2015 in 6 randomly selected health facilities in Southern Province, Zambia. For the first 5 months, circumcision clients >=18 years of age were given referral vouchers that allowed them to refer up to 5 peers for circumcision within a 3-month period. An incentive of US$2 was offered for each referral. The primary outcome was the number of circumcisions performed per month in each facility. To assess the effect of the intervention, a difference-in-difference analysis was performed using longitudinal data from the intervention facilities and 22 nonintervention facilities. A questionnaire was also implemented to understand men's perceptions of the intervention. RESULTS: During the 8-month intervention period, 1222 men over 18 years of age were circumcised in intervention facilities. In the first 5 months, 699 circumcision clients were enrolled and 385 clients brought a referral voucher given to them by an enrolled client. Difference-in-difference analyses did not show a significant increase in circumcisions performed in intervention facilities. However, circumcision clients reported that the referral incentive motivated them to encourage their friends to seek male circumcision. Peer referrals were also reported to be an important factor in men's decisions because 78% of clients who were referred reported that talking with a circumcised friend was important for their decision to get circumcised. CONCLUSIONS: The peer referral incentive intervention for male circumcision was feasible and acceptable. However, the intervention did not have a significant effect on demand for male circumcision. Barriers to circumcision and features of the intervention may have limited the effect of the intervention. Further efforts regarding encouraging male-to-male communication and evaluations with larger sample sizes are needed. PMID- 27404007 TI - The Impact of SMS-Based Interventions on VMMC Uptake in Lusaka Province, Zambia: A Randomized Controlled Trial. AB - INTRODUCTION: Zambia has high HIV prevalence and low voluntary medical male circumcision (VMMC) rates, heightening the need for effective VMMC demand generation strategies for HIV prevention. METHODS: A 3-arm randomized controlled trial measured the impact of 2 short message service (SMS) campaigns on self reported and verified VMMC uptake over 6 months in Lusaka Province. The study enrolled 2312 uncircumcised males aged 15-30 previously subscribed on Zambia U Report, an existing SMS platform providing confidential, free counseling services relevant to HIV and other sexually transmitted infections. Participants in the "Conventional" campaign group received a standard package of messages promoting VMMC. Messages sent to the "Tailored" campaign group were targeted at participants' intention level to get circumcised. The control group had routine counselor access through SMS. Data were collected using SMS surveys, and verification of self-reported VMMC uptake used health facility client data. RESULTS: Six-month self-reported VMMC uptake was 11.6%, 12.6%, and 10.4% in the Conventional, Tailored, and control arms, respectively; verified uptake was 1.8%, 1.1%, and 1.5%. Using multivariate logistic regression, the adjusted odds ratio of self-reported VMMC uptake was 1.17 (95% CI: 0.80 to 1.72) in the Conventional campaign arm compared with the control arm and 1.24 (95% CI: 0.84 to 1.81) in the Tailored campaign arm. The adjusted odds ratios of verified VMMC uptake in the Conventional and Tailored campaign arms were 1.34 (95% CI: 0.45 to 4.02) and 0.67 (95% CI: 0.20 to 2.23), respectively. CONCLUSIONS: Neither SMS campaign had statistically significant impact on VMMC uptake compared with routine SMS counseling. Future research is necessary to fully understand the potential of SMS based tools for VMMC demand creation. PMID- 27404008 TI - Innovative Demand Creation for Voluntary Medical Male Circumcision Targeting a High Impact Male Population: A Pilot Study Engaging Pregnant Women at Antenatal Clinics in Kampala, Uganda. AB - BACKGROUND: Circumcision has been shown to be an effective method of HIV prevention; however, only 27% of Ugandan men aged 15-49 years are circumcised. There is a paucity of data on the role of intimate partners in generating demand for voluntary medical male circumcision (VMMC). We conducted a pilot study to assess the feasibility of a partner-focused intervention targeting males >25 years. METHODS: Among pregnant women in their third trimester attending antenatal care we evaluated the impact of a pilot behavior change intervention on VMMC through a quasi-experimental approach. We observed VMMC numbers among spouses of women as per standard practice (comparison phase), and after introducing a behavioral change communication package (intervention phase). Logistic regression was used to compare the odds of VMMC uptake between comparison and intervention phases. We used qualitative methods to evaluate the casual chain using a thematic approach. RESULTS: Of the 601 women studied, 90% articulated the health benefits of VMMC and 99% expressed interest in their spouse getting circumcised. Women's knowledge was not increased by the intervention. Four men were circumcised in the comparison and 7 in the intervention phase. The intervention was not associated with higher odds of circumcision (odds ratio 1.5, 95% CI: 0.3 to 6.0, P = 0.65). We interviewed 117 individuals overall with the main enablers for VMMC being: free VMMC, transport reimbursement, and health benefits. Deterrents included misconceptions, lost wages and fear of pain. Most of the uncircumcised men interviewed reported interest in VMMC. CONCLUSIONS: Our pilot intervention had no significant impact on increasing VMMC demand. The study demonstrated the feasibility of pregnant women engaging their spouses to discuss VMMC. PMID- 27404009 TI - A Randomized Evaluation of a Demand Creation Lottery for Voluntary Medical Male Circumcision Among Adults in Tanzania. AB - BACKGROUND: Uptake of voluntary medical male circumcision (VMMC) among adult men has fallen short of targets in Tanzania. We evaluated a smartphone raffle intervention designed to increase VMMC uptake in three regions. METHODS: Among 7 matched pairs of health facilities, 1 in each pair was randomly assigned to the intervention, consisting of a weekly smartphone raffle for clients returning for follow-up and monthly raffle for peer promoters and providers. VMMC records of clients aged 20 and older were analyzed over three months, with the number performed compared with the same months in the previous year. In multivariable models, the intervention's effect on number of VMMCs was adjusted for client factors and clustering. Focus groups with clients and peer promoters explored preferences for VMMC incentives. RESULTS: VMMCs increased 47% and 8% in the intervention and control groups, respectively; however, the changes were not significantly different from one another. In the Iringa region subanalysis, VMMCs in the intervention group increased 336% (exponentiated coefficient of 3.36, 95% CI: 1.14 to 9.90; P = 0.028), after controlling for facility pair, percentage of clients >= age 30, and percentage testing HIV positive; the control group had a more modest 63% significant increase (exponentiated coefficient 1.63, 95% CI: 1.18 to 2.26; P = 0.003). The changes were not significantly different. Focus group respondents expressed mixed opinions about smartphone raffles; some favored smaller cash incentive or transportation reimbursement. IMPLICATIONS: A smartphone raffle might increase VMMC uptake in some settings by helping late adopters move from intention to action; however, there is no recommendation for this intervention more generally. PMID- 27404010 TI - Advertising for Demand Creation for Voluntary Medical Male Circumcision. AB - OBJECTIVE: To measure the effects of information, a challenge, and a conditional cash transfer on take-up of voluntary medical male circumcision (VMMC). DESIGN: A randomized, controlled experiment with 4000 postcard recipients in Soweto (Johannesburg), South Africa. METHODS: We examined differences in take-up of several decisions in the VMMC cascade between the control arm and each of several intervention arms using logistic regression. RESULTS: Logistic regression analysis indicated that the group offered US $10 as compensation and the group challenged with "Are you tough enough?" had significantly higher take-up of the VMMC procedure than did the control group [odds ratios, respectively, 5.30 (CI: 2.20 to 12.76) and 2.70 (CI: 1.05 to 6.91)]. Similarly, the compensation group had significantly higher take-up of the VMMC counseling session than did the control group [odds ratio 3.76 (CI: 1.79 to 7.89)]. The analysis did not reveal significantly different take-up of either the VMMC counseling session or the procedure in the partner preference information group compared with the control group [odds ratios, respectively, 1.23 (CI: 0.51 to 2.97) and 1.67 (CI: 0.61 to 4.62)]. The analysis did not reveal significantly higher take-up of the VMMC nurse hotline in any intervention group compared with the control group [odds ratios for US $10, information, and challenge, respectively, 1.17 (CI: 0.67 to 2.07), 0.69 (CI: 0.36 to 1.32), and 0.60 (0.31 to 1.18)]. CONCLUSIONS: Among adult males in Soweto, South Africa, compensation of US $10 provided conditional on completing the VMMC counseling session compared with no compensation offer and a postcard with a challenge, "Are you tough enough?" compared with no challenge, resulted in moderate increases in take-up of circumcision. PMID- 27404011 TI - A Sport-Based Intervention to Increase Uptake of Voluntary Medical Male Circumcision Among Adolescent Male Students: Results From the MCUTS 2 Cluster Randomized Trial in Bulawayo, Zimbabwe. AB - BACKGROUND: Mathematical models suggest that 570,000 HIV infections could be averted between 2011 and 2025 in Zimbabwe if the country reaches 80% voluntary medical male circumcision (VMMC) coverage among 15- to 49-year-old male subjects. Yet national coverage remains well below this target, and there is a need to evaluate interventions to increase the uptake. METHODS: A cluster-randomized trial was conducted to assess the effectiveness of Make-The-Cut-Plus (MTC+), a single, 60-minute, sport-based intervention to increase VMMC uptake targeting secondary school boys (14-20 years). Twenty-six schools in Bulawayo, Zimbabwe, were randomized to either receive MTC+ at the start (intervention) or end (control) of a 4-month period (March to June 2014). VMMC uptake over these 4 months was measured via probabilistic matching of participants in the trial database (n = 1226 male participants; age, 14-20 years; median age, 16.2 years) and the registers in Bulawayo's 2 free VMMC clinics (n = 5713), using 8 identifying variables. RESULTS: There was strong evidence that the MTC+ intervention increased the odds of VMMC uptake by approximately 2.5 fold (odds ratio = 2.53; 95% confidence interval, 1.21 to 5.30). Restricting to participants who did not report being already circumcised at baseline, MTC+ increased VMMC uptake by 7.6% (12.2% vs 4.6%, odds ratio = 2.65; 95% confidence interval, 1.19 to 5.86). Sensitivity analyses related to the probabilistic matching did not change these findings substantively. The number of participants who would need to be exposed to the demand creation intervention to yield one additional VMMC client was 22.7 (or 13.2 reporting not already being circumcised). This translated to approximately US dollar 49 per additional VMMC client. CONCLUSIONS: The MTC+ intervention was an effective and cost-effective strategy for increasing VMMC uptake among school-going adolescent male subjects in Bulawayo. PMID- 27404012 TI - The Effects of Providing Fixed Compensation and Lottery-Based Rewards on Uptake of Medical Male Circumcision in Kenya: A Randomized Trial. AB - BACKGROUND: Effective demand creation strategies are needed to increase uptake of medical male circumcision and reduce new HIV infections in eastern and southern Africa. Building on insights from behavioral economics, we assessed whether providing compensation for opportunity costs of time or lottery-based rewards can increase male circumcision uptake in Kenya. METHODS: Uncircumcised men aged 21-39 years were randomized in 1:1:1 ratio to 2 intervention groups or a control group. One intervention group was offered compensation of US $12.50 conditional on circumcision uptake. Compensation was provided in the form of food vouchers. A second intervention group was offered the opportunity to participate in a lottery with high-value prizes on undergoing circumcision. The primary outcome was circumcision uptake within 3 months. RESULTS: Among 903 participants enrolled, the group that received compensation of US $12.50 had the highest circumcision uptake (8.4%, 26/308), followed by the lottery-based rewards group (3.3%, 10/302), and the control group (1.3%, 4/299). Logistic regression analysis showed that compared with the control group, the fixed compensation group had significantly higher circumcision uptake [adjusted odds ratio 7.1; 95% CI: 2.4 to 20.8]. The lottery-based rewards group did not have significantly higher circumcision uptake than the control group (adjusted odds ratio 2.5; 95% CI: 0.8 to 8.1). CONCLUSIONS: Providing compensation was effective in increasing circumcision uptake among men over a short period. The results are consistent with studies showing that such interventions can modify health behaviors by addressing economic barriers and behavioral biases in decision making. Contrary to findings from studies of other health behaviors, lottery-based rewards did not significantly increase circumcision uptake. TRIAL REGISTRATION: Registry for International Development Impact Evaluations: RIDIE-STUDY-ID-530e60df56107. PMID- 27404013 TI - Use of Economic Compensation to Increase Demand for Voluntary Medical Male Circumcision in Kenya: Qualitative Interviews With Male Participants in a Randomized Controlled Trial and Their Partners. AB - BACKGROUND: Interventions to increase demand for medical male circumcision are urgently needed in eastern and southern Africa. Following promising evidence that providing economic compensation can increase male circumcision uptake in Kenya, there is a need to understand the role of this intervention in individuals' decision-making regarding circumcision and explore perceptions of the intervention and concerns such as coercion. METHODS: As part of a randomized controlled trial in Kenya that found compensation in the form of food vouchers worth US $8.75-US $15.00 to be effective in increasing male circumcision uptake, we conducted qualitative in-depth interviews with 45 circumcised and uncircumcised male participants and 19 female partners to explore how compensation provision influenced the decision to get circumcised. Interview transcripts were coded and an inductive thematic analysis was conducted to identify patterns in decision-making. RESULTS: Interviews revealed that compensation promoted circumcision uptake by addressing a major barrier to male circumcision uptake: lost wages during and after the circumcision procedure. Participants who did not get circumcised perceived the compensation amounts to be insufficient for offsetting their costs associated with getting circumcised or reported having nonfinancial barriers that were not addressed by the intervention, such as fear of pain. Participants also reported that they did not feel compelled to get circumcised for financial gain. Female partners of circumcised participants felt that the intervention helped to motivate their partners to get circumcised. CONCLUSIONS: The results suggest that the provision of economic compensation is an acceptable intervention that can address an important barrier to male circumcision uptake. Providing compensation to circumcision clients in the form of food vouchers warrants further consideration in voluntary medical male circumcision demand creation efforts. PMID- 27404014 TI - Contacting dropouts from type 2 diabetes care in public primary health care: description of the patient population. AB - OBJECTIVE: To characterize dropouts from type-2 diabetes (T2D) care in communal primary health care. DESIGN: An observational study. SETTING: In a Finnish city, patients with T2D who had not contacted the public primary health care system during the past 12 months were identified with a computer based search and contacted by a trained diabetes nurse. SUBJECTS: Dropouts from T2D treatment. MAIN OUTCOME MEASURES: Demographic factors, laboratory parameters, examinations, medications, and comorbidities. RESULTS: Of the patients with T2D, 10% (n = 356) were dropouts and 60% of them were men. Median HbA1c was 6.5 (QR for 25% and 75%: 6.0, 7.7) %, (45 [42,61] mmol/mol). Of the dropouts, 14% had HbA1c >= 9.0% (75 mmol/mol), and these patients were younger than the other dropouts (mean age 54.4 [SD 10.8] years vs. 60.6 [9.4] years, p < 0.001). Median low-density lipoprotein (LDL) cholesterol level was 2.8 (QR 2.1, 3.4) mmol/l. Median systolic blood pressure (BP) was 142 (QR 130, 160) mm Hg. Median diastolic BP was 86 (78, 94) mm Hg. Of the dropouts, 83% had comorbidities and 62% were prescribed metformin as a treatment. CONCLUSIONS: Ten percent of T2D patients were dropouts of whom those with a poor glycaemic control were younger than the other dropouts. BP and LDL cholesterol concentrations were non-optimal among the majority of the dropouts. Metformin was prescribed less frequently to the dropouts than is usual for T2D patients. The comorbidities were equally common among the dropouts as among the other T2D patients. KEY POINTS Which kinds of patients are dropouts from type-2 diabetes care is not known. * One-tenth of the patients with T2D were dropouts and they generally had good glycaemic control. * Blood pressure and LDL cholesterol concentrations were non-optimal among the majority of the dropouts. * Fourteen percent of these dropouts had HbA1c > 9% (75 mmol/mol) and they were more often younger than the other dropouts. PMID- 27404015 TI - Interplay of Ion-Water and Water-Water Interactions within the Hydration Shells of Nitrate and Carbonate Directly Probed with 2D IR Spectroscopy. AB - The long-range influence of ions in solution on the water hydrogen-bond (H-bond) network remains a topic of vigorous debate. Recent spectroscopic and theoretical studies have, for the most part, reached the consensus that weakly coordinating ions only affect water molecules in the first hydration shell. Here, we apply ultrafast broadband two-dimensional infrared (2D IR) spectroscopy to aqueous nitrate and carbonate in neat H2O to study the solvation structure and dynamics of ions on opposite ends of the Hofmeister series. By exciting both the water OH stretches and ion stretches and probing the associated cross-peaks between them, we are afforded a comprehensive view into the complex nature of ion hydration. We show in aqueous nitrate that weak ion-water H-bonding leads to water-water interactions in the ion solvation shells dominating the dynamics. In contrast, the carbonate CO stretches show significant mixing with the water OH stretches due to strong ion-water H-bonding such that the water and ion modes are intimately correlated. Further, the excitonic nature of vibrations in neat H2O, which spans multiple water molecules, is an important factor in describing ion hydration. We attribute these complex dynamics to the likely presence of intermediate-range effects influenced by waters beyond the first solvation shell. PMID- 27404016 TI - Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats. AB - AIMS: Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD. MAIN METHODS: Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression. KEY FINDINGS: No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (+/-LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and +/-LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP. SIGNIFICANCE: CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses. PMID- 27404017 TI - Characterization of Aqueous Oleic Acid/Oleate Dispersions by Fluorescent Probes and Raman Spectroscopy. AB - Oleic acid (OA) and oleates form self-assembled structures dispersible in aqueous media. Herein, the physicochemical properties of OA/oleate assemblies were characterized using fluorescent probes and Raman spectroscopy, under relatively high dilution (<100 mM of total amphiphile) at 25 degrees C. Anisotropy analysis using 1,6-diphenyl-1,3,5-hexatriene showed that the microviscosity of the OA/oleate assembly was highest at pH 7.5 (the pH range of 6.9-10.6 was investigated). The fluorescence spectra of 6-lauroyl-2-dimethylaminonaphthalene revealed the dehydrated environments on membrane surfaces at pH < 7.7. The pH dependent Raman peak intensity ratios, chain torsion (S = I1124/I1096) and chain packing (R = I2850/I2930), showed local maxima, indicating the occurrence of metastable phases, such as dispersed cubic phase (pH = 7.5), vesicle (pH = 8.5), and dispersed cylindrical micelle (pH = 9.7). These results suggest that large scale OA/oleate assemblies could possess particular membrane properties in a narrow pH region, e.g., at pH 7.5, and 9.7. PMID- 27404019 TI - Electrorheological Source of Nonlinear Dielectric Effects in Molecular Glass Forming Liquids. AB - We have measured the dielectric relaxation spectra of eight glass-forming liquids in the presence of electric direct current (dc)-bias fields ranging from 100 to 500 kV/cm. For every sample, we observe two distinct field-induced effects: a reduction in the relaxation amplitude and an increase in the primary structural relaxation time that is associated with viscous flow. Whereas amplitude change is typical of the well-known dielectric saturation, the field-induced increase in viscosity is a source of nonlinear behavior that has been recognized only recently. We find that this electrorheological behavior occurs in all polar liquids of this study, and its magnitude is correlated with the field-induced change in thermodynamic entropy. It constitutes a significant source of nonlinear dielectric behavior, which occurs for both dc and alternating current fields. PMID- 27404018 TI - Synthesis of Indole-2-carboxylate Derivatives via Palladium-Catalyzed Aerobic Amination of Aryl C-H Bonds. AB - A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from 2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures. PMID- 27404022 TI - Future Papers. PMID- 27404020 TI - Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism. AB - BACKGROUND: Thrombospondin-1 (THBS-1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS-1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial mesenchymal transition (EMT), and expression of other relevant molecules. METHODS: Ninety-four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS-1 (THBS-1 high [n = 35] and THBS-1 low [n = 59]) and tumor growth, Ki-67 labeling index (Ki 67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated. RESULTS: THBS-1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS-1 expression (3-year survival: 96.7% vs. 65.4%, P < 0.01). Multivariate analysis identified THBS-1 low expression as an independent prognostic factor (HR 2.82, 95% CI 1.21-7.71, P = 0.01). THBS-1 low expression correlated positively with high Ki-67 LI (P < 0.05) and inversely with E-cadherin (P < 0.05) and hypoxia inducible factor-1alpha (HIF-1alpha) expression (P < 0.05); THBS-1 expression and MVD were not significantly correlated. CONCLUSIONS: Low THBS-1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS-1 may be regulated by the HIF-1 pathway. PMID- 27404021 TI - Hospital Noninvasive Ventilation Case Volume and Outcomes of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Higher hospital case volume may produce local expertise ("practice makes perfect"), resulting in better patient outcomes. Associations between hospital noninvasive ventilation (NIV) case volume and outcomes for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) are unclear. OBJECTIVES: To determine associations between total hospital NIV case volume for all indications and NIV failure and hospital mortality among patients with acute exacerbations of COPD. METHODS: Using the 2011 California State Inpatient Database and multivariable hierarchical logistic regression, we calculated hospital-level risk-adjusted rates for NIV failure (progression from NIV to invasive mechanical ventilation) and hospital mortality among patients with acute exacerbations of COPD. MEASUREMENTS AND MAIN RESULTS: We identified 37,516 hospitalizations for acute exacerbations of COPD in 252 California hospitals in 2011. Total hospital NIV use for all indications ranged from 2 to 565 cases (median, 64; interquartile range, 96). Hospital NIV failure rates for acute exacerbations of COPD ranged from 3.7 to 31.3% (median, 8.5%; interquartile range, 4.2). At the hospital level, higher total hospital NIV case volume was weakly associated with higher hospital NIV failure rates for acute exacerbations of COPD (r = 0.13; P = 0.03). Higher hospital NIV failure rates were weakly associated with higher hospital mortality rates for acute exacerbations of COPD (r = 0.15; P = 0.02), but higher total hospital NIV case volume was not associated with hospital mortality for exacerbations of COPD (r = -0.11; P = 0.08). At the patient level, patients admitted to high-NIV versus low-NIV case volume hospitals had greater odds of NIV failure (quartile 4 vs. quartile 1 adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.12-3.40). Compared with initial treatment with invasive mechanical ventilation, NIV failure was associated with higher odds of death (aOR, 1.81; 95% CI, 1.35-2.44). However, admission to high-NIV versus low-NIV case-volume hospitals was not significantly associated with patient in-hospital mortality (quartile 4 vs. quartile 1 aOR, 0.76; 95% CI, 0.57-1.02). CONCLUSIONS: Despite strong evidence for use of NIV in the management of acute exacerbations of COPD, we observed no significant mortality benefit and higher rates of NIV failure in high-NIV case-volume hospitals. Further investigation of patient selection and hospital factors associated with NIV failure is needed to maximize favorable patient outcomes associated with use of NIV for acute exacerbations of COPD. PMID- 27404023 TI - Insulin-Mediated Downregulation of Apolipoprotein A-I Gene in Human Hepatoma Cell Line HepG2: The Role of Interaction Between FOXO1 and LXRbeta Transcription Factors. AB - Apolipoprotein A-I (ApoA-I) is a key component of high density lipoproteins which possess anti-atherosclerotic and anti-inflammatory properties. Insulin is a crucial mediator of the glucose and lipid metabolism that has been implicated in atherosclerotic and inflammatory processes. Important mediators of insulin signaling such as Liver X Receptors (LXRs) and Forkhead Box A2 (FOXA2) are known to regulate apoA-I expression in liver. Forkhead Box O1 (FOXO1) is a well-known target of insulin signaling and a key mediator of oxidative stress response. Low doses of insulin were shown to activate apoA-I expression in human hepatoma HepG2 cells. However, the detailed mechanisms for these processes are still unknown. We studied the possible involvement of FOXO1, FOXA2, LXRalpha, and LXRbeta transcription factors in the insulin-mediated regulation of apoA-I expression. Treatment of HepG2 cells with high doses of insulin (48 h, 100 nM) suppresses apoA-I gene expression. siRNAs against FOXO1, FOXA2, LXRbeta, or LXRalpha abrogated this effect. FOXO1 forms a complex with LXRbeta and insulin treatment impairs FOXO1/LXRbeta complex binding to hepatic enhancer and triggers its nuclear export. Insulin as well as LXR ligand TO901317 enhance the interaction between FOXA2, LXRalpha, and hepatic enhancer. These data suggest that high doses of insulin downregulate apoA-I gene expression in HepG2 cells through redistribution of FOXO1/LXRbeta complex, FOXA2, and LXRalpha on hepatic enhancer of apoA-I gene. J. Cell. Biochem. 118: 382-396, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27404024 TI - OptSSeq: High-Throughput Sequencing Readout of Growth Enrichment Defines Optimal Gene Expression Elements for Homoethanologenesis. AB - The optimization of synthetic pathways is a central challenge in metabolic engineering. OptSSeq (Optimization by Selection and Sequencing) is one approach to this challenge. OptSSeq couples selection of optimal enzyme expression levels linked to cell growth rate with high-throughput sequencing to track enrichment of gene expression elements (promoters and ribosome-binding sites) from a combinatorial library. OptSSeq yields information on both optimal and suboptimal enzyme levels, and helps identify constraints that limit maximal product formation. Here we report a proof-of-concept implementation of OptSSeq using homoethanologenesis, a two-step pathway consisting of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) that converts pyruvate to ethanol and is naturally optimized in the bacterium Zymomonas mobilis. We used OptSSeq to determine optimal gene expression elements and enzyme levels for Z. mobilis Pdc, AdhA, and AdhB expressed in Escherichia coli. By varying both expression signals and gene order, we identified an optimal solution using only Pdc and AdhB. We resolved current uncertainty about the functions of the Fe2+-dependent AdhB and Zn2+-dependent AdhA by showing that AdhB is preferred over AdhA for rapid growth in both E. coli and Z. mobilis. Finally, by comparing predictions of growth linked metabolic flux to enzyme synthesis costs, we established that optimal E. coli homoethanologenesis was achieved by our best pdc-adhB expression cassette and that the remaining constraints lie in the E. coli metabolic network or inefficient Pdc or AdhB function in E. coli. OptSSeq is a general tool for synthetic biology to tune enzyme levels in any pathway whose optimal function can be linked to cell growth or survival. PMID- 27404025 TI - Alternative approaches for the treatment of airway diseases: focus on nanoparticle medicine. AB - Despite the various treatment options and international guidelines currently available for the appropriate therapeutic management of asthma, a large population of patients with asthma continues to have poorly controlled disease. There is therefore a need for novel approaches to achieve better asthma control, especially for severe asthmatics. This review discusses the use of nanoparticles for the specific targeting of inflammatory pathways as a promising approach for the effective control of severe persistent asthma as well as other chronic inflammatory diseases. PMID- 27404026 TI - Most bothersome symptom in women with genitourinary syndrome of menopause as a moderator of treatment effects. AB - OBJECTIVE: Conjugated estrogens/bazedoxifene (CE/BZA) is indicated to treat moderate/severe menopausal vasomotor symptoms and prevent postmenopausal osteoporosis. This analysis examines the impact of the most bothersome vaginal symptom at baseline on effects of CE/BZA. METHODS: This post hoc analysis used data from a 12-week clinical trial of nonhysterectomized postmenopausal women (n = 664) randomly assigned to double-blind treatment with CE/BZA (0.45/20 mg and 0.625/20 mg), BZA 20 mg, or placebo. At baseline, women indicated which moderate/severe vaginal symptom (dryness, itching/irritation, or pain with intercourse) bothered them most. Repeated measures models were used to explore treatment effects in relationship to the most bothersome symptom. We calculated effect sizes for treatment differences versus placebo (effect sizes: trivial, 0.1; small, 0.2; medium, 0.5; large, 0.8). RESULTS: At baseline, 52% of women selected pain with intercourse, 35% selected vaginal dryness, and 13% selected vaginal itching/irritation as most bothersome. For these three symptom groups respectively, CE/BZA was associated with statistically significant improvements in Menopause-Specific Quality of Life sexual functioning (effect size: 0.45/20 mg, -0.36, -0.30, -0.67; 0.625/20 mg, -0.37, -0.40, -0.26) and/or overall score (effect size: 0.45/20 mg, -0.29, -0.41, -0.78; 0.625/20 mg, -0.41, -0.48, -0.68). Both those doses significantly improved the ease of lubrication item on the Arizona Sexual Experiences Scale in those with pain with intercourse (effect size: 0.45/20 mg, -0.43; 0.625/20 mg, -0.50) and produced some statistically significant improvements in vaginal cell counts in women with dryness or pain with intercourse as the most bothersome symptom. The higher dose was associated with greater treatment satisfaction on the Menopause Symptoms Treatment Satisfaction Questionnaire versus placebo in women who selected pain with intercourse (effect size: 0.40) or dryness (effect size: 0.43) as most bothersome. CONCLUSIONS: The approved dose of CE/BZA had clear benefits, particularly in women with pain with intercourse (the most common bothersome symptom), in whom it improved lubrication, superficial cell counts, and sexual functioning. PMID- 27404027 TI - Ospemifene's effect on vasomotor symptoms: a post hoc analysis of phase 2 and 3 clinical data. AB - OBJECTIVE: To examine the effect of ospemifene 60 mg/d on vasomotor symptoms in postmenopausal women using clinical safety and efficacy data from five phase 2 and 3 studies. METHODS: The incidence of hot flush treatment-emergent adverse events (TEAEs) was compiled from five randomized, placebo-controlled clinical studies; baseline parameters associated with hot flush incidence were also identified. Ospemifene's effects on the frequency and severity of hot flushes were evaluated in a previously unpublished, 6-week, placebo-controlled study. RESULTS: Analysis of pooled hot flush TEAE data for 2,166 women showed an incidence of hot flush of 8.5% for ospemifene and 3.2% for placebo (P < 0.0001). Hot flushes were most frequent during the first 4 weeks of ospemifene treatment and decreased in frequency thereafter. Logistic regression analysis revealed that hormone therapy within 6 months before study start (P = 0.0234), longer study treatment duration (P = 0.0234), and more hot flush days per month at baseline (P = 0.0313) were associated with more hot flushes. Ospemifene 60 mg/d did not worsen the frequency and severity of existing hot flushes in a 6-week, placebo controlled trial of 198 postmenopausal women who were experiencing moderate to very severe hot flushes. CONCLUSIONS: In randomized trials, hot flush TEAEs were more frequent with ospemifene 60 mg/d than with placebo, particularly among women with prior history of hormone therapy use. The majority of hot flushes, however, waned after 4 weeks of ospemifene treatment. Ospemifene did not worsen existing hot flushes in women experiencing moderate to very severe hot flushes. PMID- 27404028 TI - Relationship between changes in vasomotor symptoms and changes in menopause specific quality of life and sleep parameters. AB - OBJECTIVE: This study characterizes and quantifies the relationship of vasomotor symptoms (VMS) of menopause with menopause-specific quality of life (MSQOL) and sleep parameters to help predict treatment outcomes and inform treatment decision making. METHODS: Data were derived from a 12-week randomized, double-blind, placebo-controlled phase 3 trial that evaluated effects of two doses of conjugated estrogens/bazedoxifene on VMS in nonhysterectomized postmenopausal women (N = 318, mean age = 53.39) experiencing at least seven moderate to severe hot flushes (HFs) per day or at least 50 per week. Repeated measures models were used to determine relationships between HF frequency and severity and outcomes on the Menopause-Specific Quality of Life questionnaire and the Medical Outcomes Study sleep scale. Sensitivity analyses were performed to check assumptions of linearity between VMS and outcomes. RESULTS: Frequency and severity of HFs showed approximately linear relationships with MSQOL and sleep parameters. Sensitivity analyses supported assumptions of linearity. The largest changes associated with a reduction of five HFs and a 0.5-point decrease in severity occurred in the Menopause-Specific Quality of Life vasomotor functioning domain (0.78 for number of HFs and 0.98 for severity) and the Medical Outcomes Study sleep disturbance (7.38 and 4.86) and sleep adequacy (-5.60 and -4.66) domains and the two overall sleep problems indices (SPI: 5.17 and 3.63; SPII: 5.82 and 3.83). CONCLUSIONS: Frequency and severity of HFs have an approximately linear relationship with MSQOL and sleep parameters-that is, improvements in HFs are associated with improvements in MSQOL and sleep. Such relationships may enable clinicians to predict changes in sleep and MSQOL expected from various VMS treatments. PMID- 27404029 TI - Characterizing the trajectories of vasomotor symptoms across the menopausal transition. AB - OBJECTIVE: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women. METHODS: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling. RESULTS: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory. CONCLUSIONS: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS. PMID- 27404030 TI - Measuring hot flash phenomenonology using ambulatory prospective digital diaries. AB - OBJECTIVE: This study provides the description, protocol, and results from a novel prospective ambulatory digital hot flash phenomenon diary. METHODS: This study included 152 midlife women with daily hot flashes who completed an ambulatory electronic hot flash diary continuously for the waking hours of three consecutive days. In this diary, women recorded their hot flashes and accompanying characteristics and associations as the hot flashes occurred. RESULTS: Self-reported hot flash severity on the digital diaries indicated that the majority of hot flashes were rated as mild (41.3%) or moderate (43.7%). Severe (13.1%) and very severe (1.8%) hot flashes were less common. Hot flash bother ratings were rated as mild (43%), or moderate (33.5%), with fewer hot flashes reported bothersome (17.5%) or very bothersome (6%). The majority of hot flashes were reported as occurring on the face (78.9%), neck (74.7%), and chest (61.3%). Of all reported hot flashes, 32% occurred concurrently with prickly skin, 7% with anxiety, and 5% with nausea. A novel finding from the study was that 38% of hot flashes were accompanied by a premonitory aura. CONCLUSIONS: A prospective electronic digital hot flash diary allows for a more precise quantitation of hot flashes while overcoming many of the limitations of commonly used retrospective questionnaires and paper diaries. Unique insights into the phenomenology, loci, and associated characteristics of hot flashes were obtained using this device. The digital hot flash phenomenology diary is recommended for future ambulatory studies of hot flashes as a prospective measure of the hot flash experience. PMID- 27404031 TI - Short-term effects of low-dose estradiol on endothelial function and blood viscosity in nondiabetic postmenopausal overweight women: a double-blind, placebo controlled study. AB - OBJECTIVE: The beneficial effects of estrogen on endothelial function depend on its integrity. This study evaluates the short-term effects of low-dose transdermal estradiol on endothelial function, insulin sensitivity, and blood viscosity in nondiabetic overweight/obese women. METHODS: Forty-four nondiabetic overweight/obese women with a history of recent menopause were randomly allocated, in a double-blind fashion, to receive transdermal estradiol (1 mg/d, n = 22) or placebo (n = 22). The following parameters were assessed: endothelial reactivity (venous occlusion plethysmography and nailfold videocapillaroscopy), plasma levels of soluble adhesion molecules, insulin sensitivity (homeostasis model assessment of insulin resistance and areas under the curve of insulin and glucose during an oral glucose tolerance test), and blood and plasma viscosity. Data were expressed as means +/- SD or medians [first to third quartiles]. RESULTS: Participants were aged 51.8 +/- 2.3 years with a body mass index of 31.5 +/- 2.5 kg/m and time since menopause was 3 [2-5] years. At baseline, no differences between the groups were observed; however, after 3 months of treatment, the following changes were observed in the estradiol group compared with the placebo group: a decrease in the forearm vascular resistance at baseline (36.37 [24.9-51.27] vs 51.3 [40.88-70.03] mm Hg/mL per min 100 mL tissue, P < 0.01) and during the postocclusive reactive hyperemia response (15.93 [11.32 22.29] vs 22.13 [16.46-29.7] mm Hg/mL per min 100 mL tissue, P < 0.01), and an increase in red blood cell velocity at rest (0.316 [0.309-0.326] vs 0.303 [0.293 0.308] mm/s, P < 0.001) and during postocclusive reactive hyperemia response (0.374 [0.353-0.376] vs 0.341 [0.333-0.355] mm/s, P < 0.001). Furthermore, blood viscosity was lower in the estradiol group than in the placebo group (3.57 +/- 0.12 vs 3.76 +/- 0.22 mPa.s; P < 0.01). CONCLUSIONS: Short-term use of low-dose transdermal estradiol in nondiabetic overweight/obese women with a history of recent menopause improved endothelial function and decreased blood viscosity compared with placebo. PMID- 27404032 TI - An assessment of the safety and efficacy of a fractional CO2 laser system for the treatment of vulvovaginal atrophy. AB - OBJECTIVES: The aim of the study was to assess the safety and efficacy of a novel fractional CO2 laser for the treatment of genitourinary syndrome of menopause (GSM). METHODS: Women presenting with GSM and meeting study criteria were enrolled. Examinations at baseline and follow-up (3 mo after final treatment) evaluated dilator tolerance and vaginal pH. Visual analog scales were used to assess pain, vaginal burning, vaginal itching, vaginal dryness, dyspareunia, and dysuria; Vaginal Health Index scores were completed before each treatment and at follow-up; Female Sexual Function Index and Short Form 12 questionnaires were also completed. Participant satisfaction was measured on a 5-point Likert scale (1 = very dissatisfied, 5 = very satisfied). Women received three laser treatments, 6 weeks apart. RESULTS: Thirty women participated (mean age 58.6 +/- 8.8 y). None withdrew or were discontinued due to an adverse event; three were lost to follow-up. Average improvement in visual analog scale scoring was 1.7 +/- 3.2 for pain, 1.4 +/- 2.9 for burning, 1.4 +/- 1.9 for itching, 6.1 +/- 2.7 for dryness, 5.1 +/- 3.0 for dyspareunia, and 1.0 +/- 2.4 for dysuria; improvement in average Vaginal Health Index and Female Sexual Function Index scores were statistically significant (P < 0.001). Twenty-five of 30 participants (83%) showed increase in comfortable dilator size at 3-month follow up. Before the second and third treatments, 86.6% (26 of 30) of women reported they were better or much better than at the previous treatment; 26 of 27 women (96%) were reportedly satisfied or extremely satisfied at follow-up. CONCLUSIONS: In this sample, the data suggest that the fractional CO2 laser is effective and safe for treatment of the symptoms associated with GSM. PMID- 27404033 TI - Stretch it and lose it: the potential benefits of a stretching intervention for the reduction of menopausal symptoms. PMID- 27404034 TI - Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials. AB - OBJECTIVE: Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials. METHODS: Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region. RESULTS: There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores -1.05 and -0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001). CONCLUSIONS: Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss. PMID- 27404035 TI - Highly selective defluoridation of brick tea infusion by tea waste supported aluminum oxides. AB - BACKGROUND: Brick tea usually contains very high fluoride, which may affect human health. Biosorbents have received much attention for selective removal of fluoride because of low cost, environmental friendliness, and relative safeness. RESULTS: In the present study, a highly selective fluoride tea waste based biosorbent, namely, aluminum (Al) oxide decorated tea waste (Tea-Al), was successfully prepared. The Tea-Al biosorbent was characterized by energy dispersive spectrometry, Fourier transform infrared spectroscopy, powder X-ray diffraction and X-ray photoelectron spectroscopic analysis. The Tea-Al sample exhibited remarkably selective adsorption for fluoride (52.90%), but a weaker adsorption for other major constituents of brick tea infusion, such as catechins, polyphenols and caffeine, under the same conditions. Fluoride adsorption by Tea Al for different times obeyed the surface reaction and adsorption isotherms fit the Freundlich model. In addition, the fluoride adsorption mechanism appeared to be an ion exchange between hydroxyl and fluoride ions. CONCLUSION: Results from this study demonstrated that Tea-Al is a promising biosorbent useful for the removal of fluoride in brick tea infusion. (c) 2016 Society of Chemical Industry. PMID- 27404036 TI - DNA Methylation Profiling in Chondrocyte Dedifferentiation In Vitro. AB - DNA methylation has emerged as a crucial regulator of chondrocyte dedifferentiation, which severely compromises the outcome of autologous chondrocyte implantation (ACI) treatment for cartilage defects. However, the full scale DNA methylation profiling in chondrocyte dedifferentiation remains to be determined. Here, we performed a genome-wide DNA methylation profiling of dedifferentiated chondrocytes in monolayer culture and chondrocytes treated with DNA methylation inhibitor 5-azacytidine (5-AzaC). This research revealed that the general methylation level of CpG was increased while the COL-1A1 promoter methylation level was decreased during the chondrocyte dedifferentiation. 5-AzaC could reduce general methylation levels and reverse the chondrocyte dedifferentiation. Surprisingly, the DNA methylation level of COL-1A1 promoter was increased after 5-AzaC treatment. The COL-1A1 expression level was increased while that of SOX-9 was decreased during the chondrocyte dedifferentiation. 5 AzaC treatment up-regulated the SOX-9 expression while down-regulated the COL-1A1 promoter activity and gene expression. Taken together, these results suggested that differential regulation of the DNA methylation level of cartilage-specific genes might contribute to the chondrocyte dedifferentiation. Thus, the epigenetic manipulation of these genes could be a potential strategy to counteract the chondrocyte dedifferentiation accompanying in vitro propagation. J. Cell. Physiol. 232: 1708-1716, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27404037 TI - A novel quantitation approach for maximizing detectable targets for offensive/volatile odorants with diverse functional groups by thermal desorption gas chromatography-mass spectrometry. AB - A multitude of analytical systems are needed to analyze diverse odorants with various functionalities. In this study, an experimental method was developed to assess the maximum covering range of odorants using a single experimental setup consisting of a thermal desorber-gas chromatography-mass spectrometry system. To this end, a total of 20 offensive odorants (aldehyde, ketone, ester, alcohol, aromatic, sulfide, amine, and carboxyl) were selected and tested by a single system. The analytical results of standards and environmental samples were evaluated in a number of respects. In the analysis of the standards, all targets were quantified via Carbopack (C + B + X) tube sampling while operating the thermal desorber at -25 degrees C. The method detection limits of 18 targets (exception of 2 out of the 20 targets: acetaldehyde and methanethiol) were excellent (mean 0.04 +/- 0.03 ppb) in terms of their odor threshold values (74.7 +/- 140 ~ 624 +/- 1,729 ppb). The analysis of organic fertilizer plant samples at a pig farm (slurry treatment facility, compost facility, and ambient air) confirmed the presence of 18 odorants from 0.03 ppb (dimethyldisulfide, ambient sample) to 522 ppb (methyl ethyl ketone, slurry treatment facility). As such, our method allowed simultaneous quantitation of most key odorants with sufficient reliability and sensitivity. PMID- 27404038 TI - Circulating cell-free mature microRNAs and their target gene prediction in bovine metritis. AB - Uterine infections in dairy cows are common after calving, reduce fertility and cause substantial economic losses. Conventional diagnosis (based on clinical signs) and treatment can be challenging. Serum microRNA (miRNA) profiles serve as non-invasive biomarkers in several pathological conditions including inflammatory diseases. The objective was to identify differentially expressed serum miRNAs in cows with metritis and normal uterus (four cows per group), integrate miRNAs to their target genes, and categorize target genes for biological processes involved in bacterial infection and inflammatory responses. Out of 84 bovine-specific, prioritized miRNAs analyzed, 30 were differentially expressed between metritis and normal cows (p <= 0.05, fold regulation >=2 magnitudes). Bta-miR-15b, bta-miR 17-3p, bta-miR-16b, bta-miR-148a, bta-miR-26b, bta-miR-101 and bta-miR-29b were highly up-regulated whereas bta-miR-148b, bta-miR-199a-3p, bta-miR-122, bta-miR 200b and bta-miR-10a were highly down-regulated in cows with metritis compared to cows with normal uterus. Highly scored target genes of up-regulated and down regulated miRNAs were categorized for various biological processes, including biological regulation, cellular process, developmental process, metabolic process, localization, multicellular organismal process, response to stimulus, immune system process, cellular components organization, apoptotic process, biological adhesion, developmental process, and locomotion that are critical to combat bacterial infections and provoke inflammatory responses. PMID- 27404040 TI - The first demonstration of RNA interference to inhibit mRNA function. AB - I review how RNA interference was discovered for the first time in 1984 in our laboratory. PMID- 27404039 TI - Cost-Savings Analysis of AR-V7 Testing in Patients With Metastatic Castration Resistant Prostate Cancer Eligible for Treatment With Abiraterone or Enzalutamide. AB - INTRODUCTION: Identification of cancer biomarkers that inform clinical decisions and reduce the use of ineffective therapies is a major goal of precision oncology. An abnormal splice variant of the androgen receptor, AR-V7, was recently found to confer resistance to novel hormonal therapies (abiraterone and enzalutamide) in men with metastatic castration-resistant prostate cancer (mCRPC), but did not negatively affect responses to taxane chemotherapies, suggesting that early use of chemotherapy may be a more effective option for AR V7(+) patients. METHODS: We calculated the cost savings of performing AR-V7 testing in mCRPC patients prior to starting abiraterone/enzalutamide (and avoiding these drugs in AR-V7(+) men) versus treating all mCRPC patients empirically with abiraterone/enzalutamide (without use of the biomarker). RESULTS: We determined that AR-V7 testing would result in substantial cost savings as long as the true prevalence of AR-V7 was >5%. In our prior studies, we estimated that approximately 30% of mCRPC patients may have detectable AR-V7 in circulating tumor cells (CTCs). In this population, upfront testing of AR-V7 status (at a price of $1,000 per test) would result in a net cost savings of $150 Million in the United States per year. CONCLUSIONS: AR-V7 testing in mCRPC patients would be cost-beneficial when considering the current price of treatment, and may reduce the ineffective use of abiraterone/enzalutamide, leading to a significant net cost savings to the healthcare system. Clinical grade AR-V7 testing is currently available at our institution. Prostate 76:1484 1490, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27404041 TI - Insights into the molecular phylogeny and historical biogeography of the white clawed crayfish (Decapoda, Astacidae). AB - In this study, the evolutionary history of the white-clawed crayfish (WCC) was evaluated using large-scale datasets comprising >1350 specimens from the entire distribution range. Using species delimitation methods on mitochondrial DNA (mtDNA) sequences, we propose four primary species hypotheses for WCC. Sequences for several nuclear regions were screened but none showed significant variation within WCC. This result favours a single secondary species hypothesis and indicates the existence of a mito-nuclear discordance in WCC. Therefore, mtDNA groups were considered only as genetic units that carry information about ancient divergences within WCC and not as taxonomic units. The reconstruction of ancestral ranges and divergence time estimates were used to link the current genetic structure with paleogeographic processes. These results showed that the emergence of mtDNA groups in WCC could be related to the Messinian Salinity Crisis, the climate cooling during the Pliocene and Pleistocene, and (paleo)shifting of the Adriatic Sea coastline in the Padanovenezian Plain. The most recent common ancestor of the mtDNA groups most likely originated from Dalmatia (eastern Adriatic coast) as indicated by the reconstruction of ancestral ranges. This ecoregion, along with the Gulf of Venice Drainages, harbours a high genetic diversity and should be emphasised as an area of the highest conservation priority. PMID- 27404042 TI - Two-step evolution of endosymbiosis between hydra and algae. AB - In the Hydra vulgaris group, only 2 of the 25 strains in the collection of the National Institute of Genetics in Japan currently show endosymbiosis with green algae. However, whether the other non-symbiotic strains also have the potential to harbor algae remains unknown. The endosymbiotic potential of non-symbiotic strains that can harbor algae may have been acquired before or during divergence of the strains. With the aim of understanding the evolutionary process of endosymbiosis in the H. vulgaris group, we examined the endosymbiotic potential of non-symbiotic strains of the H. vulgaris group by artificially introducing endosymbiotic algae. We found that 12 of the 23 non-symbiotic strains were able to harbor the algae until reaching the grand-offspring through the asexual reproduction by budding. Moreover, a phylogenetic analysis of mitochondrial genome sequences showed that all the strains with endosymbiotic potential grouped into a single cluster (cluster gamma). This cluster contained two strains (J7 and J10) that currently harbor algae; however, these strains were not the closest relatives. These results suggest that evolution of endosymbiosis occurred in two steps; first, endosymbiotic potential was gained once in the ancestor of the cluster gamma lineage; second, strains J7 and J10 obtained algae independently after the divergence of the strains. By demonstrating the evolution of the endosymbiotic potential in non-symbiotic H. vulgaris group strains, we have clearly distinguished two evolutionary steps. The step-by-step evolutionary process provides significant insight into the evolution of endosymbiosis in cnidarians. PMID- 27404043 TI - A reinvestigation of phylogeny and divergence times of the Ablepharus kitaibelii species complex (Sauria, Scincidae) based on mtDNA and nuDNA genes. AB - Morphological and DNA data support that the East Mediterranean snake-eyed skink Ablepharus kitaibelii represents a species complex that includes four species A. kitaibelii, A. budaki, A. chernovi, and A. rueppellii, highlighting the need of its taxonomic reevaluation. Here, we used Bayesian and Maximum Likelihood methods to estimate the phylogenetic relationships of all members of the complex based on two mitochondrial (cyt b, 16S rRNA) and two nuclear markers (MC1R, and NKTR) and using Chalcides, Eumeces, and Eutropis as outgroups. The biogeographic history of the complex was also investigated through the application of several phylogeographic (BEAST) and biogeographic (BBM) analyses. Paleogeographic and paleoclimatic data were used to support the inferred phylogeographic patterns. The A. kitaibelli species complex exhibits high genetic diversity, revealing cases of hidden diversity and cases of non-monophyletic species such as A. kitaibelii and A. budaki. Our results indicate that A. pannonicus branches off first and a group that comprises specimens of A. kitaibelli and A. budaki from Kastelorizo Island group (southeast Greece) and southwest Turkey, respectively is differentiated from the rest A. kitaibelli and A. budaki populations and may represent a new species. The estimated divergence times place the origin of the complex in the Middle Miocene (~16Mya) and the divergence of most currently recognized species in the Late Miocene. The inferred ancestral distribution suggests that the complex originated in Anatolia, supposing that several vicariance and dispersal events that are related with the formation of the Mid Aegean Trench, the Anatolian Diagonal and the orogenesis of the mountain chains in southern and eastern Anatolia have led to current distribution pattern of A. kitaibelii species complex in the Balkans and Middle East. PMID- 27404044 TI - Perioperative Predictors of Extubation Failure and the Effect on Clinical Outcome After Infratentorial Craniotomy. AB - BACKGROUND The purpose of the study was to analyze the risk factors for failed extubation in subjects submitted to infratentorial craniotomy. MATERIAL AND METHODS Patients aged over 18 years who received infratentorial craniotomy for brain tumor resection were consecutively included in this study. Perioperative variables were collected and analyzed. Univariate analyses and multiple logistic regression were used to derive factors related to failed extubation. Patients had follow-up care until either out of hospital or death. RESULTS Throughout the course of the study, 2118 patients were eligible and 94 (4.4%) suffered from extubation failure at some point during their hospital stay. Five factors were recognized as independent risk factors for postoperative failed extubation: craniotomy history, preoperative lower cranial nerve dysfunction, tumor size, tumor position, and maximum change in blood pressure (BP) during the operation. Failed extubation was related to a higher incidence rate of pneumonia, mortality, unfavorable Glasgow Outcome Scale score, longer stay in the neuro-intensive care unit (ICU) and hospitalization, and higher hospitalization costs compared with successful extubation. CONCLUSIONS History of craniotomy, preoperative lower cranial nerve dysfunction, tumor size, tumor position, and maximum change in BP during the operation were independent risk factors related to postoperative failed extubation in patients submitted to infratentorial craniotomy. Extubation failure raises the incidences of postoperative pneumonia, mortality, and higher hospitalization costs, and prolongs neuro-ICU and postoperative length of stay. PMID- 27404045 TI - Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting. AB - Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5+ B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017. PMID- 27404046 TI - Loss of lipopolysaccharide-binding protein attenuates the development of diet induced non-alcoholic fatty liver disease in mice. AB - BACKGROUND AND AIM: It has been suggested in several studies that an increased translocation of bacterial lipopolysaccharide (LPS) and, subsequently, an activation of toll-like receptor (TLR)-dependent signaling pathways in the liver may contribute to the development of non-alcoholic fatty liver disease. METHODS: Eight-week-old lipopolysaccharide-binding protein (LBP)-/- and wild-type (WT) mice were pair fed either a liquid diet rich in fat, fructose, and cholesterol (Western-style diet [WSD]) or a control liquid diet for 8 weeks. Parameters of liver injury, markers of TLR-4-dependent signaling pathway, and glucose/lipid metabolism were determined. RESULTS: Despite similar total caloric intake, weight gain, fasting blood glucose levels, and liver-to-bodyweight ratio, indices of liver damage determined by liver histology and transaminases were markedly lower in WSD-fed LBP-/- mice than in WSD-fed WT animals. In line with these findings, number of neutrophils, F4/80 positive cells, and plasminogen activator inhibitor 1 were only found to be significantly increased in livers of WSD-fed WT mice. While mRNA expressions of TLR-4 and myeloid differentiation primary response 88 were similar between WSD-fed groups, concentrations of inducible nitric oxide synthase protein and 4-hydroxynonenal protein adducts were significantly higher in livers of WSD-fed WT mice than in WSD-fed LBP-/- animals. Markers of lipid metabolism, for example, sterol regulatory element-binding protein 1c and fatty acid synthase per se, were significantly lower in livers of LBP-/- mice; however, mRNA expressions did not differ between controls and WSD-fed mice within the respective mouse strain. CONCLUSION: Taken together, our results suggest that LBP is a critical factor in the development of non-alcoholic fatty liver disease in mice. PMID- 27404047 TI - Cosmid based mutagenesis causes genetic instability in Streptomyces coelicolor, as shown by targeting of the lipoprotein signal peptidase gene. AB - Bacterial lipoproteins are extracellular proteins tethered to cell membranes by covalently attached lipids. Deleting the lipoprotein signal peptidase (lsp) gene in Streptomyces coelicolor results in growth and developmental defects that cannot be restored by reintroducing lsp. This led us to hypothesise that lsp is essential and that the lsp mutant we isolated previously had acquired compensatory secondary mutations. Here we report resequencing of the genomes of wild-type M145 and the cis-complemented ?lsp mutant (BJT1004) to map and identify these secondary mutations but we show that they do not increase the efficiency of disrupting lsp and are not lsp suppressors. We provide evidence that they are induced by introducing the cosmid St4A10?lsp, as part of ReDirect PCR mutagenesis protocol, which transiently duplicates a number of important cell division genes. Disruption of lsp using a suicide vector (which does not result in gene duplication) still results in growth and developmental delays and we conclude that loss of Lsp function results in developmental defects due to the loss of all lipoproteins from the cell membrane. Significantly, our results also indicate the use of cosmid libraries for the genetic manipulation of bacteria can lead to phenotypes not necessarily linked to the gene(s) of interest. PMID- 27404048 TI - Engineered biomaterial and biophysical stimulation as combinatorial strategies to address prosthetic infection by pathogenic bacteria. AB - A plethora of antimicrobial strategies are being developed to address prosthetic infection. The currently available methods for implant infection treatment include the use of antibiotics and revision surgery. Among the bacterial strains, Staphylococcus species pose significant challenges particularly, with regard to hospital acquired infections. In order to combat such life threatening infectious diseases, researchers have developed implantable biomaterials incorporating nanoparticles, antimicrobial reinforcements, surface coatings, slippery/non adhesive and contact killing surfaces. This review discusses a few of the biomaterial and biophysical antimicrobial strategies, which are in the developmental stage and actively being pursued by several research groups. The clinical efficacy of biophysical stimulation methods such as ultrasound, electric and magnetic field treatments against prosthetic infection depends critically on the stimulation protocol and parameters of the treatment modality. A common thread among the three biophysical stimulation methods is the mechanism of bactericidal action, which is centered on biophysical rupture of bacterial membranes, the generation of reactive oxygen species (ROS) and bacterial membrane depolarization evoked by the interference of essential ion-transport. Although the extent of antimicrobial effect, normally achieved through biophysical stimulation protocol is insufficient to warrant therapeutic application, a combination of antibiotic/ROS inducing agents and biophysical stimulation methods can elicit a clinically relevant reduction in viable bacterial numbers. In this review, we present a detailed account of both the biomaterial and biophysical approaches for achieving maximum bacterial inactivation. Summarizing, the biophysical stimulation methods in a combinatorial manner with material based strategies can be a more potent solution to control bacterial infections. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2174 2190, 2017. PMID- 27404049 TI - The study of the paranemic crossover (PX) motif in the context of self-assembly of DNA 2D crystals. AB - This manuscript systematically studies the self-assembly behavior of the paranemic crossover (PX) motif in the context of DNA 2D crystallization. The PX structure is a class of DNA nanomotifs that has been suggested as a model for DNA homologous recognition in cells and, more importantly, used as a cohesion mechanism/building block (tile) for DNA nanoconstruction. However, there is no vigorous examination on the relationship between structural variation and assembly behavior. The lack of this essential information prevents us from applying the PX motif to complex nanoconstruction. In this study, we have devised a system that allows us to systematically examine this relationship and found the best PX motif that best suits the assembly of 2D crystals. PMID- 27404050 TI - Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats. AB - Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire-mediated RF hyperthermia (42 degrees C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% +/- 7, 44.6% +/ 7.5, 95.8% +/- 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 +/- 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 * 107 photons per second per square millimeter +/- 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 +/- 0.13, P < .05) and relative photon signal (0.56 * 107 photons per second per square millimeter +/- 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy on esophageal squamous cell cancers. (c) RSNA, 2016. PMID- 27404051 TI - Control of Granule Cell Dispersion by Natural Materials Such as Eugenol and Naringin: A Potential Therapeutic Strategy Against Temporal Lobe Epilepsy. AB - The hippocampus is an important brain area where abnormal morphological characteristics are often observed in patients with temporal lobe epilepsy (TLE), typically showing the loss of the principal neurons in the CA1 and CA3 areas of the hippocampus. TLE is frequently associated with widening of the granule cell layer of the dentate gyrus (DG), termed granule cell dispersion (GCD), in the hippocampus, suggesting that the control of GCD with protection of hippocampal neurons may be useful for preventing and inhibiting epileptic seizures. We previously reported that eugenol (EUG), which is an essential component of medicinal herbs and has anticonvulsant activity, is beneficial for treating epilepsy through its ability to inhibit GCD via suppression of mammalian target of rapamycin complex 1 (mTORC1) activation in the hippocampal DG in a kainic acid (KA)-treated mouse model of epilepsy in vivo. In addition, we reported that naringin, a bioflavonoid in citrus fruits, could exert beneficial effects, such as antiautophagic stress and antineuroinflammation, in the KA mouse model of epilepsy, even though it was unclear whether naringin might also attenuate the seizure-induced morphological changes of GCD in the DG. Similar to the effects of EUG, we recently observed that naringin treatment significantly reduced KA induced GCD and mTORC1 activation, which are both involved in epileptic seizures, in the hippocampus of mouse brain. Therefore, these observations suggest that the utilization of natural materials, which have beneficial properties such as inhibition of GCD formation and protection of hippocampal neurons, may be useful in developing a novel therapeutic agent against TLE. PMID- 27404052 TI - Radiation awareness among dentists, radiographers and students. AB - OBJECTIVES: The aim of this study was to assess radiation awareness among dentists, radiographers, dentistry students and radiography students from the Medical University of Warsaw. METHODS: A questionnaire containing 13 multiple choice questions was administered to 200 dentists, 200 radiographers, 100 dentistry students and 100 radiography students. Participants were asked about basic knowledge concerning dental radiological examinations. RESULTS: In total, 301 (50.2%) questionnaires were returned. The mean score of correct answers was 8.13 out of 13 for all responders; 8.36 for dentists, 8.11 for radiographers, 8.19 for dentistry students and 7.46 for radiography students. Range of correct answers varied from 3 to 12. Differences between the four main groups were not statistically significant. Dentists who had completed radiation protection training had significantly higher number of correct answers than untrained dentists. For radiographers, the level of education had no connection with the results. Correlation between year of the study and results was not visible in the dentistry student group. Within the radiography student group, students in the third year of the study had significantly higher number of correct answers than those in the first and second years of the study. CONCLUSIONS: Our survey shows that radiation awareness among dentists, radiographers and students is inadequate, without significant differences in the main groups. Dentists who had completed radiation protection training had better awareness than those without such training. Greater emphasis should be put on the dental radiology course in both dentistry and radiography programmes at universities. PMID- 27404055 TI - SAGE Publications is Now the Publisher of American Journal of Health Promotion. PMID- 27404053 TI - Clinical acceptability study of micronized purified flavonoid fraction 1000 mg tablets versus 500 mg tablets in patients suffering acute hemorrhoidal disease. AB - OBJECTIVE: To compare the clinical acceptability of micronized purified flavonoid fraction (MPFF) 1000 mg with MPFF 500 mg tablets, administered at the same daily dose in patients suffering non-complicated acute hemorrhoids. BACKGROUND: MPFF is an established treatment for hemorrhoidal disease. METHODS: This was a double blind, multi-center, randomized study. Patients took either MPFF 1000 mg or 500 mg tablets for 7 days (daily dose; 3 g over 4 days followed by 2 g over 3 days). Adverse events were recorded in a patient diary. On day 7, anal pain and bleeding were assessed (visual analog scale [VAS] and Dimitroulopoulos scale, respectively). RESULTS: Patients (162) were randomized to MPFF 1000 mg (79) and MPFF 500 mg (83). No serious adverse events (AEs) occurred; 10 emergent AEs were considered treatment-related (6 for MPFF 1000 mg and 4 for 500 mg). Both regimens were associated with significant reduction in anal pain (VAS); -2.37 cm MPFF 1000 mg (P < 0.001) and -2.17 cm 500 mg (P < 0.001), with a slight trend in favor of MPFF 1000 mg (mean global reduction -2.27 cm, P < 0.001). Bleeding improved significantly in both groups of patients, 56% of patients on MPFF 1000 mg versus 61% on MPFF 500 mg. Bleeding ceased after treatment in 47% patients on MPFF 1000 mg versus 54% on 500 mg. CONCLUSION: After 7 days of treatment with MPFF at the same daily dose, both regimens reduced anal pain and bleeding. MPFF 1000 mg had a comparable safety profile to MPFF 500 mg, with the advantage of fewer tablets. Key limitations: Safety study. PMID- 27404056 TI - Effects of Exercise-Based Interventions on Neonatal Outcomes: A Meta-Analysis of Randomized Controlled Trials. AB - OBJECTIVE: The aim of this study was to conduct a systematic review and meta analysis of randomized controlled clinical trials (RCTs) assessing the influence of physical exercise interventions during pregnancy on some neonatal outcomes. DATA SOURCE: Key words were used to conduct a computerized search in six databases: Cochrane Library Plus, Science Direct, EMBASE, PubMed, Web of Science, and ClinicalTrials.gov. STUDY INCLUSION AND EXCLUSION CRITERIA: RCTs that included an exercise program for healthy pregnant women who were sedentary or had low levels of physical activity were selected. DATA EXTRACTION: Two independent reviewers extracted data and assessed the quality of the studies included. Of 4296 articles retrieved, 14 RCTs (3044 pregnant women) met the inclusion criteria. DATA SYNTHESIS: Pooled effect sizes (ESs) were calculated using a fixed model. RESULTS: Overall, physical exercise programs during pregnancy produced a small reduction in neonatal birth weight (ES = -.10; p = .04). The Apgar score at 1 minute was also weakly increased with combined exercise (aerobic, strength, and flexibility) (ES = .09; p = .048) and no differences between groups were observed in gestational age at delivery and Apgar score at 5 minutes. CONCLUSION: Structured physical exercise programs during pregnancy appear to be safe for the neonate, mainly favoring a lower birth weight within normal range. However, more studies are needed to establish recommendations. PMID- 27404057 TI - The Impact of College Student Financial Health on Other Dimensions of Health. AB - PURPOSE: Researchers examined college students' financial health and other health indicators to determine whether the integration of financial health into undergraduate health courses is justified and justify financial health as the newest dimension of health within the field of health promotion. DESIGN: The study utilized a cross-sectional design. SETTING: The study was conducted at a large public university located in the western region of the United States. Participants completed the survey from any computer with Internet access. SUBJECTS: A sample of 3000 undergraduate students was selected. A total of 686 surveys were completed (22.9% response rate). Data were collected from college students ages 18 to 30 during the first 2 weeks of June 2013. MEASURES: Participants completed an online survey regarding their financial health and other dimensions of health. ANALYSIS: SPSS version 19.0 was used to examine the relationships between financial health and individual health variables using chi(2), independent t-test, analysis of variance, Pearson R, point-biserial correlation, and nonparametric analyses. RESULTS: Every dimension of health was impacted significantly by lower levels of financial health. Participants' emotional health was impacted far more than any other dimension, with significant impacts on concentration (p = .005), usefulness (p = .006), decision making (p = .014), and happiness (p < .001) by the mere presence of a budget. CONCLUSION: Findings indicate an apparent relationship between financial health and other health indicators and support the need for financial education by parents and middle/high schools and the incorporation of financial health into undergraduate health courses. PMID- 27404058 TI - Pragmatic, Randomized Controlled Trials of the Girls on the Go! Program to Improve Self-Esteem in Girls. AB - PURPOSE: To test the effectiveness of an intervention delivered by health professionals outside the school environment to girls identified with issues such as poor body image, low self-esteem, low self-confidence, nonparticipation in sports, or being overweight or underweight. DESIGN: The study's design was a stepped-wedge randomized controlled trial to test the efficacy of an intervention on self-esteem, impairment induced by eating disorders, self-efficacy, body satisfaction, and dieting behaviors. SETTING: The study took place at the community health center located in a culturally diverse area of Melbourne, Victoria, Australia. SUBJECTS: Participants were 122 primary and secondary school girls between 10 and 16 years of age. INTERVENTION: Girls on the Go! is a 10-week program designed to improve self-esteem, body image, and confidence, using an empowerment model that involved interactive and experiential learning approaches. Weekly themes included body image and self-esteem, safety and assertiveness, a healthy mind, physical activity, healthy eating, trust and confidence, and connections. MEASURES: Measurements were made using Rosenberg Self-Esteem Scale, clinical interview assessment, health self-efficacy (included mental health and physical health self-efficacy scales), body esteem scale, and the Dutch Eating Behavior Questionnaire for Children. ANALYSIS: A linear mixed model was used. RESULTS: The intervention led to a significant increase (p < .05) in self-esteem and self-efficacy (mental and physical health self-efficacy subscales), for both primary and secondary school-aged participants and reduced dieting behaviors (secondary school participants). These gains were retained after 6 months of follow-up. CONCLUSION: This group-based, low-dose intervention, which, although targeting girls with a range of psychological issues and including both overweight and underweight participants, is a successful means of improving self esteem among girls from diverse cultural backgrounds. PMID- 27404059 TI - Correlates of Reported Use and Perceived Helpfulness of Calorie Information in Restaurants Among U.S. Adults. AB - PURPOSE: This study reports correlates in reported use and helpfulness of calorie information, when available, in restaurants on a national scale in the United States for demographic behavioral and health-related conditions. DESIGN: This study is a secondary data analysis of the 2013 National Cancer Institute's Health Information National Trends Survey data. SETTING: United States. SUBJECTS: Adults (n = 3407). MEASURES: Menu labeling use and helpfulness; behavior change attempts; reported fruit, vegetable, and soda consumption; weight status; and chronic health conditions. ANALYSIS: Trends were identified in weighted logistic and linear regression models. RESULTS: U.S. adults who intended to lose weight (odds ratio [OR] = 5.01 [95% confidence interval 2.96, 8.46]), increase fruit (OR = 1.10 [.66, 1.84]) or vegetable consumption (OR = 2.25 [1.32, 3.83]), or reduce soda consumption (OR = 1.67 [1.11, 2.51]) were more likely to report using menu labeling information when available. More women reported calorie information was helpful when ordering (p < .05). Racial/ethnic and socioeconomic status disparities were identified in use (non-Hispanic [NH] blacks vs. NH whites OR = .43 [.25, .74]) and helpfulness (NH blacks vs. NH whites beta = -.06 [-.44, .32]). CONCLUSION: Findings highlight potential subgroups to target for communication and education efforts regarding use of calorie information in restaurants. Following publication of final rules for federal menu-labeling legislation and implementation, further surveillance of public response to this information may inform message framing and educational interventions to promote use of calorie information on menu boards. PMID- 27404060 TI - The Impact of Breastfeeding on Early Childhood Obesity: Evidence From the National Survey of Children's Health. AB - PURPOSE: To investigate how breastfeeding initiation and duration affect the likelihood of being overweight and obese in children aged 2 to 5. DESIGN: Cross sectional data from the 2003 National Survey of Children's Health. SETTING: Rural and urban areas of the United States. SUBJECTS: Households where at least one member was between the ages of 2 and 5 (sample size 8207). MEASURES: Parent reported body mass index, breastfeeding initiation and duration, covariates (gender, family income and education, ethnicity, child care attendance, maternal health and physical activity, residential area). ANALYSIS: Partial proportional odds models. RESULTS: In early childhood, breastfed children had 5.3% higher probability of being normal weight (p = .002) and 8.9% (p < .001) lower probability of being obese compared to children who had never been breastfed. Children who had been breastfed for less than 3 months had 3.1% lower probability of being normal weight (p = .013) and 4.7% higher probability of being obese (p = .013) with respect to children who had been breastfed for 3 months and above. CONCLUSION: Study findings suggest that length of breastfeeding, whether exclusive or not, may be associated with lower risk of obesity in early childhood. However, caution is needed in generalizing results because of the limitations of the analysis. Based on findings from this study and others, breastfeeding promotion policies can cite the potential protective effect that breastfeeding has on weight in early childhood. PMID- 27404061 TI - Effects of Community Singing Program on Mental Health Outcomes of Australian Aboriginal and Torres Strait Islander People: A Meditative Approach. AB - PURPOSE: To evaluate the impact of a meditative singing program on the health outcomes of Aboriginal and Torres Strait Islander people. DESIGN: The study used a prospective intervention design. SETTING: The study took place in six Aboriginal and Torres Strait Islander communities and Community Controlled Health Services in Queensland, Australia. SUBJECTS: Study participants were 210 Australian Aboriginal and Torres Strait Islander adults aged 18 to 71 years, of which 108 were in a singing intervention group and 102 in a comparison group. INTERVENTION: A participative community-based community singing program involving weekly singing rehearsals was conducted over an 18-month period. MEASURES: Standardized measures in depression, resilience, sense of connectedness, social support, and singing related quality of life were used. ANALYSIS: The general linear model was used to compare differences pre- and postintervention on outcome variables, and structural equation modeling was used to examine the pathway of the intervention effect. RESULTS: Results revealed a significant reduction in the proportion of adults in the singing group classified as depressed and a concomitant significant increase in resilience levels, quality of life, sense of connectedness, and social support among this group. There were no significant changes for these variables in the comparison group. CONCLUSIONS: The participatory community singing approach linked to preventative health services was associated with improved health, resilience, sense of connectedness, social support, and mental health status among Aboriginal and Torres Strait Islander adults. PMID- 27404062 TI - ''Quit & Win'' Contests Among College Students: Predictors of Long-Term Smoking Abstinence. AB - PURPOSE: To determine smoking abstinence rates and predictors of abstinence among college students enrolled in a campus-based Quit & Win contest. DESIGN: Pre-post measure with no comparison group. SETTING: Contests conducted on seven college campuses in 2007. SUBJECTS: Subjects (N = 484) were 23.7 +/- 6.8 years of age, 61% female, 16.3% nonwhite, and smoked 12.5 +/- 7.8 cigarettes per day on 28.0 +/ 4.8 days in the past month. INTERVENTION: Participants abstinent for the 30-day contest were eligible for a lottery-based prize. Assessments were completed at baseline, end of contest, and 6 months after enrollment. MEASURES: The 6-month survey assessed retrospective abstinence during the contest period and the prior 6 months and 7- and 30-day point prevalence abstinence at the time of the survey. ANALYSIS: Chi-square test was used to compare baseline characteristics among participants from 2-versus 4-year schools. Smoking abstinence was assessed by participant self-report. Both a simple imputation method (i.e., missing = smoking) and completers-only analyses were conducted. Stepwise logistic regression was used to determine baseline predictors of abstinence. RESULTS: Thirty-day abstinence rate was 52.5% during the contest month and 20.5% at the 6 month follow-up. Baseline intention to stay quit (odds ratio [OR] = 1.56, p = .01), cigarettes smoked per day (OR = .67, p = .04), and 2-year (vs. 4-year) college (OR = 1.65, p = .05) predicted abstinence at 6 months. CONCLUSION: Intention to stay quit even without winning a prize, a measure of intrinsic motivation, predicted both short- and long-term abstinence. PMID- 27404063 TI - Measuring the Processes of Change From the Transtheoretical Model for Physical Activity and Exercise in Overweight and Obese Adults. AB - PURPOSE: This study aimed to test three factorial structures conceptualizing the processes of change (POC) from the transtheoretical model and to examine the relationships between the POC and stages of change (SOC) among overweight and obese adults. DESIGN: Cross-sectional study. SETTING: This study was conducted at the University Hospital of Montpellier, France. SUBJECTS: A sample of 289 overweight or obese participants (199 women) was enrolled in the study. MEASURES: Participants completed the POC and SOC questionnaires during a 5-day hospitalization for weight management. ANALYSIS: Structural equation modeling was used to compare the different factorial structures. RESULTS: The unweighted least squares method was used to identify the best-fit indices for the five fully correlated model (goodness-of-fit statistic = .96; adjusted goodness-of-fit statistic = .95; standardized root mean residual = .062; normed-fit index = .95; parsimonious normed-fit index = .83; parsimonious goodness-of-fit statistic = .78). The multivariate analysis of variance was significant (p < .001). A post hoc test showed that individuals in advanced SOC used more of both experiential and behavioral POC than those in preaction stages, with effect sizes ranging from .06 to .29. CONCLUSION: This study supports the validity of the factorial structure of POC concerning physical activity and confirms the assumption that, in this context, people with excess weight use both experiential and behavioral processes. These preliminary results should be confirmed in a longitudinal study. PMID- 27404064 TI - The Influence of Health Literacy on Reach, Retention, and Success in a Worksite Weight Loss Program. AB - PURPOSE: To examine if employee health literacy (HL) status moderated reach, retention, and weight outcomes in a worksite weight loss program. DESIGN: The study was a two-group cluster randomized controlled weight loss trial. SETTING: The study was conducted in 28 worksites. SUBJECTS: Subjects comprised 1460 employees with a body mass index >25 kg/m(2). INTERVENTIONS: Two 12-month weight loss interventions targeted diet and physical activity behaviors: incentaHEALTH (INCENT; incentivized individually targeted Internet-based intervention) and Livin' My Weigh (LMW; less-intense quarterly newsletters). MEASURES: A validated three-item HL screening measure was self-completed at baseline. Weight was objectively assessed with the Health Spot scale at baseline and 12-month follow up. ANALYSIS: The impact of HL on program effectiveness was assessed through fixed-effect parametric models that controlled for individual (i.e., age, gender, race, ethnicity, income, education) and worksite random effects. RESULTS: Enrolled employees had significantly higher HL status [13.54 (1.68)] as compared to unenrolled [13.04 (2.17)] (p < .001). This finding was consistent in both interventions. Also, HL moderated weight loss effects (beta = .66; SE = 027; p = .014) and losing >5% weight (beta = -1.53; SE = .77; p < .047). For those with lower baseline HL, the INCENT intervention produced greater weight loss outcomes compared to LMW. The HL level of employees retained was not significantly different from those lost to follow-up. CONCLUSION: HL influences reach and moderates weight effects. These findings underscore the need to integrate recruitment strategies and further evaluate programmatic approaches that attend to the needs of low-HL audiences. PMID- 27404065 TI - Our Health Is in Our Hands: A Social Marketing Campaign to Combat Obesity and Diabetes. AB - PURPOSE: Design, implement, and evaluate a 6-week social marketing campaign (SMC) to raise awareness of obesity and increase involvement in type 2 diabetes prevention, nutrition, and fitness programs offered by the Brooklyn Partnership to Drive Down Diabetes (BP3D) in two low-income, urban communities. DESIGN: This was a nonexperimental, formative research, mixed-methods study. SETTING: The study took place in Central Brooklyn and East New York, two of the most impoverished, high-need communities in New York City. SUBJECTS: Participants were black and Hispanic adults, who were 18+ years of age and residing in the priority communities. INTERVENTION: Advertisements in English and Spanish encouraging healthier eating habits and advocating for better food options were displayed on New York City bus shelters, buses, and subway cars operating in the priority communities. Social media, Web sites, and print material were used to promote the campaign message. MEASURES: Social media metrics and a street intercept postsurvey informed the campaign's success. ANALYSIS: Quantitative data were analyzed using descriptive statistics. RESULTS: One hundred advertisements in English and Spanish were posted. After an 18-month followup, there were over 11,000 visits to the Facebook page. Results from the postsurvey (n = 171) suggest the SMC motivated participants who recognized the advertisements to improve their health behaviors. CONCLUSION: A multifaceted SMC that coincides with prevention programs can effectively raise attention to health issues and activities in a high-risk population at a relatively low cost. PMID- 27404066 TI - Multilevel Analysis of Municipal Officials' Participation in Land Use Policies Supportive of Active Living: City and Individual Factors. AB - PURPOSE: To investigate individual- and city-level factors associated with municipal officials' participation in a local land use policy that supports active living. DESIGN: Cross-sectional study. SETTING: Eighty-three cities in eight states. SUBJECTS: Four hundred thirteen elected and appointed officials with various job functions including mayors, city councilors, aldermen, selectmen, city or town managers, and heads of departments of planning, community development, public works, transportation, engineering, parks and recreation, neighborhood services, and public health. MEASURES: A Web-based survey assessed perceived importance of physical activity and livability issues to job responsibilities; perceived resident support of local government action to address physical activity and livability issues; and residence. City-level factors obtained from Census data included percentage of commuters by walking, bicycling, and public transit. The dependent variable was self-reported participation in developing, adopting, or implementing a local land use policy supportive of active living. ANALYSIS: Hierarchical (two-level: municipal official-city) logistic regression model, using R. RESULTS: Municipal officials living in the city where they worked were significantly more likely to be involved in a land use policy. Higher perceived importance of livability issues was associated with participation. Perceived importance of physical activity was inversely associated with land use policy involvement. Higher city-level bicycling rates resulted in increased odds of participation in a land use policy. City-level walking rates were inversely associated with land use policy participation. CONCLUSION: Municipal officials who worked in cities with a higher proportion of bicycle commuters, who prioritized livability issues, and who resided in the city where they worked were more likely to engage in land use policies supportive of active living. PMID- 27404067 TI - Creating a Screening Measure of Health Literacy for the Health Information National Trends Survey. AB - PURPOSE: Create a screening measure of health literacy for use with the Health Information National Trends Survey (HINTS). DESIGN: Participants completed a paper-based survey. Items from the survey were used to construct a health literacy screening measure. SETTING: A population-based survey conducted in geographic areas of high and low minority frequency and in Central Appalachia. SUBJECTS: Two thousand nine hundred four English-speaking participants were included in this study: 66% white, 93% completed high school, mean age = 52.53 years (SD = 16.24). MEASURES: A health literacy screening measure was created using four items included in the HINTS survey. Scores could range from 0 (no questions affirmative/correct) to 4 (all questions answered affirmatively/correctly). ANALYSIS: Multiple regression analysis was used to determine whether demographic variables known to predict health literacy were indeed associated with the constructed health literacy screening measure. RESULTS: The weighted average health literacy score was 2.63 (SD = 1.00). Those who were nonwhite (p = .0005), were older (p < .0005), or had not completed high school (p < .0001) tended to have lower health literacy screening measure scores. CONCLUSION: This study highlights the need to assess health literacy in national surveys, but also serves as evidence that screening measures can be created within existing datasets to give researchers the ability to consider the impact of health literacy. PMID- 27404068 TI - The Art of Health Promotion ideas for improving health outcomes. PMID- 27404069 TI - An Interview with Dr. David Katz on the "True Health Initiative.". PMID- 27404070 TI - No Time for Food. PMID- 27404071 TI - An Interview With Kevin Walker, MS, PhD, Professor, Michigan State University, The College of Veterinary Medicine, Department of Large Animal Clinical Sciences. PMID- 27404072 TI - All's Well Waconia: Changing the Way We Think About Nutrition. PMID- 27404073 TI - Could a Broader Social and Educational Diagnosis Inform Fairer Food Policies? PMID- 27404085 TI - Electronic Conduction in Ti/Poly-TiO2/Ti Structures. AB - Recent intensive investigations on metal/metal oxide/metal structures have targeted nanometric single grain oxides at high electric fields. Similar research on thicker polycrystalline oxide layers can bridge the results to the prior literature on varistors and may uncover novel ionic/electronic features originating from the conduction mechanisms involving grain boundaries. Here, we investigate electronic conduction in Ti/poly-TiO2-x/Ti structures with different oxygen vacancy distributions and describe the observed features based on the motion and rearrangement of the ionized oxygen vacancies (IOVs) on the grain facets rather than the grain interiors. Containing no interface energy barrier, Ti/poly-TiO2/Ti devices demonstrate high resistance ohmic conduction at biasing fields below 5 * 10(6) V.m(-1); higher fields drive the samples to a distinctly nonlinear and hysteretic low resistance status. The observed threshold is two orders of magnitude smaller than the typical resistance switching fields reported for the nanosized single grain memristors. This is consistent with the smaller activation energies reported for the IOV motion on the rutile facets than its interior. The presented model describes the observed dependence of the threshold field on the relative humidity of the surrounding air based on the lower activation energies reported for the hydroxyl-assisted IOV motion on the rutile facets. PMID- 27404084 TI - Evaluation on the efficiencies of county-level Centers for Disease Control and Prevention in China: results from a national survey. AB - OBJECTIVES: The Chinese government has greatly increased funding for disease control and prevention since the 2003 Severe Acute Respiration Syndrome crisis, but it is also concerned whether these increased resources have been used efficiently to improve public health services. We aimed to assess the efficiency of county-level Centers for Disease Control and Prevention (CDCs) of China and to identify strategies for optimising their performance. METHODS: A total of 446 county-level CDCs were selected based on systematic sampling throughout China. The data envelopment analysis framework was used to calculate the efficiency score of sampled CDCs in 2010. The Charnes, Cooper and Rhodes (CCR) model was applied to calculate the overall and scale efficiency, and the Banker, Charnes and Cooper (BCC) model was used to assess technical efficiency. Models included three inputs and seven outputs. A projection analysis was conducted to identify the difference between projection value and actual value for inputs and outputs. RESULTS: The average overall efficiency score of CDCs was 0.317, and the average technical efficiency score was 0.442 and 88.3% with decreasing returns to scale. Projection analysis indicated that all seven categories of outputs were underproduced. CDCs in the eastern region tended to perform better than CDCs in the middle and the western region. CONCLUSIONS: Most county-level CDCs in China were operated inefficiently. Emphasis should be put on increasing staff and general operating expenses through current governmental funding, upgrading healthcare providers' competencies and enhancing the standardisation of operational management, so that CDCs could utilise their resources more efficiently. PMID- 27404086 TI - ZIF-8 Derived, Nitrogen-Doped Porous Electrodes of Carbon Polyhedron Particles for High-Performance Electrosorption of Salt Ions. AB - Three-dimensional (3-D) ZIF-8 derived carbon polyhedrons with high nitrogen (N) content, (denoted as NC-800) are synthesized for their application as high performance electrodes in electrosorption of salt ions. The results showed a high specific capacitance of 160.8 F.g(-1) in 1 M NaCl at a scan rate of 5 mV.s(-1). Notably, integration of 3-D mesopores and micropores in NC-800 achieves an excellent capacitive deionization (CDI) performance. The electrosorption of salt ions at the electrical double layer is enhanced by N-doping at the edges of a hexagonal lattice of NC-800. As evidenced, when the initial NaCl solution concentration is 1 mM, the resultant NC-800 exhibits a remarkable CDI potential with a promising salt electrosorption capacity of 8.52 mg.g(-1). PMID- 27404088 TI - Alexandrite-like effect in purple flowers analyzed with newly devised round RGB diagram. AB - The gemstone alexandrite is known for its feature to change color depending on the spectral quality of the incident light. Thus, the stone looks green when illuminated by white LED light but looks red when illuminated by incandescent light. This effect (alexandrite effect) is caused by a special relationship between the spectral quality of the incident light and the absorbance spectrum of the stone. Here we report an alexandrite-like effect in the petals of torenia and cyclamen flowers. These flowers are purple in sunlight but magenta (reddish) in incandescent light, and violet (bluish purple) in white LED light. The m-n, triangle and round diagrams are devised to calculate the colors of visible light spectra, based on the RGB color-matching function. Using these calculations, the alexandrite-like effect in purple flowers was successfully analyzed in terms of the interaction between the incident light spectrum and the absorbance spectrum of their purple anthocyanin. This analysis allows both logical and intuitive understanding of the colors exhibited by any object showing alexandrite-like properties. PMID- 27404087 TI - Molecular cloning and functional characterization of the sex-determination gene doublesex in the sexually dimorphic broad-horned beetle Gnatocerus cornutus (Coleoptera, Tenebrionidae). AB - Various types of weapon traits found in insect order Coleoptera are known as outstanding examples of sexually selected exaggerated characters. It is known that the sex determination gene doublesex (dsx) plays a significant role in sex specific expression of weapon traits in various beetles belonging to the superfamily Scarabaeoidea. Although sex-specific weapon traits have evolved independently in various Coleopteran groups, developmental mechanisms of sex specific expression have not been studied outside of the Scarabaeoidea. In order to test the hypothesis that dsx-dependent sex-specific expression of weapon traits is a general mechanism among the Coleoptera, we have characterized the dsx in the sexually dimorphic broad-horned beetle Gnatocerus cornutus (Tenebrionidea, Tenebirionidae). By using molecular cloning, we identified five splicing variants of Gnatocerus cornutus dsx (Gcdsx), which are predicted to code four different isoforms. We found one male-specific variant (GcDsx-M), two female-specific variants (GcDsx-FL and GcDsx-FS) and two non-sex-specific variants (correspond to a single isoform, GcDsx-C). Knockdown of all Dsx isoforms resulted in intersex phenotype both in male and female. Also, knockdown of all female-specific isoforms transformed females to intersex phenotype, while did not affect male phenotype. Our results clearly illustrate the important function of Gcdsx in determining sex-specific trait expression in both sexes. PMID- 27404089 TI - Construction of Models for Nondestructive Prediction of Ingredient Contents in Blueberries by Near-infrared Spectroscopy Based on HPLC Measurements. AB - Nondestructive prediction of ingredient contents of farm products is useful to ship and sell the products with guaranteed qualities. Here, near-infrared spectroscopy is used to predict nondestructively total sugar, total organic acid, and total anthocyanin content in each blueberry. The technique is expected to enable the selection of only delicious blueberries from all harvested ones. The near-infrared absorption spectra of blueberries are measured with the diffuse reflectance mode at the positions not on the calyx. The ingredient contents of a blueberry determined by high-performance liquid chromatography are used to construct models to predict the ingredient contents from observed spectra. Partial least squares regression is used for the construction of the models. It is necessary to properly select the pretreatments for the observed spectra and the wavelength regions of the spectra used for analyses. Validations are necessary for the constructed models to confirm that the ingredient contents are predicted with practical accuracies. Here we present a protocol to construct and validate the models for nondestructive prediction of ingredient contents in blueberries by near-infrared spectroscopy. PMID- 27404090 TI - Decadal variability of tropical tropopause temperature and its relationship to the Pacific Decadal Oscillation. AB - Tropopause temperatures (TPTs) control the amount of stratospheric water vapour, which influences chemistry, radiation and circulation in the stratosphere, and is also an important driver of surface climate. Decadal variability and long-term trends in tropical TPTs as well as stratospheric water vapour are largely unknown. Here, we present for the first time evidence, from reanalysis and state of-the-art climate model simulations, of a link between decadal variability in tropical TPTs and the Pacific Decadal Oscillation (PDO). The negative phase of the PDO is associated with anomalously cold sea surface temperatures (SSTs) in the tropical east and central Pacific, which enhance the zonal SST gradient across the equatorial Pacific. The latter drives a stronger Walker Circulation and a weaker Hadley Circulation, which leads to less convection and subsequently a warmer tropopause over the central equatorial Pacific. Over the North Pacific, positive sea level pressure anomalies occur, which damp vertical wave propagation into the stratosphere. This in turn slows the Brewer-Dobson circulation, and hence warms the tropical tropopause, enabling more water vapour to enter the stratosphere. The reverse chain of events holds for the positive phase of the PDO. Such ocean-troposphere-stratosphere interactions may provide an important feedback on the Earth's global surface temperature. PMID- 27404091 TI - Competitive Excimer Formation and Energy Transfer in Zr-Based Heterolinker Metal Organic Frameworks. AB - The spectroscopy and dynamics of a series of Zr-based MOFs in dichloromethane suspension are reported. These Zr-NADC MOFs were constructed by using different mixtures of 2,6-naphthalenedicarboxylate (NDC) and 4-amino-2,6 naphthalenedicarboxylate (NADC) as organic linkers. The fraction of NADC relative to NDC in these heterolinker MOFs ranges from 2 to 35 %. The results indicate two competitive photoprocesses: NDC excimer formation and an energy transfer (ET) from excited NDC linkers to NADC linkers. Increasing the fraction of NADC linkers in the Zr-NADC nanostructure decreases the mean time constant of NDC excimer formation, while the NADC emission intensity experiences a drop at the highest fraction of this linker in the MOF. The first observation is explained by an increase in the energy-transfer probability between the two linkers, and the second by emission quenching in the NADC linkers due to ultrafast charge transfer assisted by the amino group. Femtosecond time-resolved emission studies showed that the ET process (recorded as decaying and rising components) from excited NDC to NADC takes place in 1.2 ps. Direct excitation of the NADC linkers (at 410 nm) shows a decaying, but not rising, component of 250-480 fs, which could reflect the formation of a nonemissive charge-separation state. The results show that by using MOFs having heterolinkers it is possible to trigger and tune excimer formation and ET processes. PMID- 27404092 TI - Genome Editing in Astyanax mexicanus Using Transcription Activator-like Effector Nucleases (TALENs). AB - Identifying alleles of genes underlying evolutionary change is essential to understanding how and why evolution occurs. Towards this end, much recent work has focused on identifying candidate genes for the evolution of traits in a variety of species. However, until recently it has been challenging to functionally validate interesting candidate genes. Recently developed tools for genetic engineering make it possible to manipulate specific genes in a wide range of organisms. Application of this technology in evolutionarily relevant organisms will allow for unprecedented insight into the role of candidate genes in evolution. Astyanax mexicanus (A. mexicanus) is a species of fish with both surface-dwelling and cave-dwelling forms. Multiple independent lines of cave dwelling forms have evolved from ancestral surface fish, which are interfertile with one another and with surface fish, allowing elucidation of the genetic basis of cave traits. A. mexicanus has been used for a number of evolutionary studies, including linkage analysis to identify candidate genes responsible for a number of traits. Thus, A. mexicanus is an ideal system for the application of genome editing to test the role of candidate genes. Here we report a method for using transcription activator-like effector nucleases (TALENs) to mutate genes in surface A. mexicanus. Genome editing using TALENs in A. mexicanus has been utilized to generate mutations in pigmentation genes. This technique can also be utilized to evaluate the role of candidate genes for a number of other traits that have evolved in cave forms of A. mexicanus. PMID- 27404093 TI - Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy. AB - PURPOSE: The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. MATERIALS AND METHODS: Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. RESULTS: The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 degrees C for bare tissue, it was 19 degrees C for tissue embedded with gold nanostructures and 38 degrees C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. CONCLUSIONS: A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided. PMID- 27404094 TI - Engagement, Retention, and Progression to Type 2 Diabetes: A Retrospective Analysis of the Cluster-Randomised "Let's Prevent Diabetes" Trial. AB - BACKGROUND: Prevention of type 2 diabetes mellitus (T2DM) is a global priority. Let's Prevent Diabetes is a group-based diabetes prevention programme; it was evaluated in a cluster-randomised trial, in which the primary analysis showed a reduction in T2DM (hazard ratio [HR] 0.74, 95% CI 0.48-1.14, p = 0.18). We examined the association of engagement and retention with the Let's Prevent Diabetes prevention programme and T2DM incidence. METHODS AND FINDINGS: We used data from a completed cluster-randomised controlled trial including 43 general practices randomised to receive either standard care or a 6-h group structured education programme with an annual refresher course for 2 y. The primary outcome was progression to T2DM at 3 y. The characteristics of those who attended the initial education session (engagers) versus nonengagers and those who attended all sessions (retainers) versus nonretainers were compared. Risk reduction of progression to T2DM by level of attendance was compared to standard care. Eight hundred and eighty participants were recruited, with 447 to the intervention arm, of which 346 (77.4%) were engagers and 130 (29.1%) were retainers. Retainers and engagers were more likely to be older, leaner, and nonsmokers than nonretainers/nonengagers. Engagers were also more likely to be male and be from less socioeconomically deprived areas than nonengagers. Participants who attended the initial session and at least one refresher session were less likely to develop T2DM compared to those in the control arm (30 people of 248 versus 67 people of 433, HR 0.38 [95% CI 0.24-0.62]). Participants who were retained in the programme were also less likely to develop T2DM compared to those in the control arm (7 people of 130 versus 67 people of 433, HR 0.12 [95% CI 0.05-0.28]). Being retained in the programme was also associated with improvements in glucose, glycated haemoglobin (HbA1c), weight, waist circumference, anxiety, quality of life, and daily step count. Given that the data used are from a clinical trial, those taking part might reflect a more motivated sample than the population, which should be taken into account when interpreting the results. CONCLUSIONS: This study suggests that being retained/engaged in a relatively low-resource, pragmatic diabetes prevention programme for those at high risk is associated with reductions in the progression to T2DM in comparison to those who receive standard care. Nonengagers and nonretainers share similar high-risk traits. Service providers of programmes should focus on reaching these hard-to-reach groups. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN80605705. PMID- 27404096 TI - [Leitlinienarbeit im Bereich Naturheilkunde und Komplementarmedizin - das Potenzial ist noch lange nicht erschopft]. PMID- 27404095 TI - Recombinant HLA-G as Tolerogenic Immunomodulant in Experimental Small Bowel Transplantation. AB - The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX). Allogenic ITX was performed in rats (Brown Norway to Lewis) with and without HLA-G treatment. It was found that HLA-G treatment significantly reduced histologically proven ACR at both an early and late postoperative timepoint (POD 4/7), concomitant to a functionally preserved graft contractility at POD 7. Interestingly, graft infiltration by myeloperoxidase+ cells was significantly reduced at POD7 by HLA-G treatment. Moreover, HLA-G treatment showed an effect on the allogenic T-cell immune response as assessed by flow cytometry: The influx of recipient-derived CD8+ T cells into the graft mesenteric lymphnodes at POD7 was significantly reduced while CD4+ populations were not affected. As a potential mechanism of action, an induction of T-reg populations in the mesenteric lymphnodes was postulated, but flow cytometric analysis of classical CD4+/CD25+/FoxP3+Treg-cells showed no significant alteration by HLA-G treatment. The novel therapeutic approach using recombinant HLA-G5 reported herein demonstrates a significant immunosuppressive effect in this model of allogenic experimental intestinal transplantation. This effect may be mediated via inhibition of recipient-derived CD8+ T-cell populations either directly or by induction of non-classical Treg populations. PMID- 27404097 TI - [Naturheilkunde in Leitlinien: David Sackett und die frischen Frisuren]. PMID- 27404098 TI - [Journal Club]. PMID- 27404099 TI - [Berucksichtigung von Wechsel- und Nebenwirkungen bei pflanzlichen Arzneimitteln in deutschen S3-Leitlinien der AWMF]. AB - Pflanzliche Arzneimittel haben in der medizinischen Versorgung im deutschsprachigen Raum eine lange Tradition, werden aber bei der Erstellung medizinischer Leitlinien selten berucksichtigt. In einer Vorstudie wurde von unserer Arbeitsgruppe aufgearbeitet, in welchem Ausmabeta sie in den aktuellen interdisziplinar, evidenz- und konsensusbasiert erstellten S3-Leitlinien der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) Beachtung gefunden haben. Ziel der jetzigen Studie war es, zu analysieren, inwieweit Neben- bzw. Wechselwirkungen von pflanzlichen Arzneimitteln in diesen S3-Leitlinien diskutiert werden. Im Januar 2015 wurden 134 S3-Leitlinien gezahlt und analysiert. 27,6% (n = 37) weisen insgesamt 194 Statements unter dem Begriff "Phytotherapie" auf. Hinweise zu Neben- und Wechselwirkungen finden sich in 28,4% der Statements (n = 55), die bei 13,9% (n = 27) durch Literatur belegt werden. 14 dieser Statements betreffen Nahrungserganzungsmittel und Ahnliches, 11 sind pauschale Aussagen zur Phytotherapie, 7 fassen mindestens 2 Arzneipflanzen pauschal zusammen. Damit weisen nur 23 Statements auf Neben- bzw. Wechselwirkungen von einzelnen Arzneipflanzen hin, 14 davon sind mit Literaturstellen belegt. Diese Ergebnisse entsprechen bei Weitem nicht den geforderten Standards der AWMF. Dafur verantwortlich sind insbesondere unprazise Begrifflichkeiten sowie eine unzureichende Systematik bei der Suche nach wissenschaftlicher Evidenz fur die Unbedenklichkeit von Arzneipflanzen Zubereitungen. Die Gesellschaft fur Phytotherapie kann hier einen wichtigen Beitrag zur Qualitatsverbesserung leisten. PMID- 27404100 TI - [A Systematic Review of Phytotherapy for Acute Rhinosinusitis]. AB - Herbal medicine is a promising alternative in the treatment of acute rhinosinusitis (ARS). We performed a systematic review for phytopharmaceutical treatments of ARS. A computerized search of databases (Cochrane Library, PubMed, and Scopus) up to 16 September 2015 was performed. Randomized controlled trials (RCTs) and controlled trials (CTs) were included and assessed using the Cochrane risk of bias tool. Seven trials on Pelargonium sidoides (EPs 7630, Umckaloabo(r)), Myrtol (GeloMyrtol(r) forte), BNO 1016 (Sinupret(r) extract), BNO 101 (Sinupret(r)), Cyclamen europaeum (Nasodren(r)), and Esberitox(r) were included. Risk of bias was heterogeneous. EPs 7630 appeared to be useful in the treatment of ARS. Myrtol showed benefits against a placebo compound, and BNO 1016 and BNO 101 might be helpful; however, there was little evidence for the effectiveness of Cyclamen europaeum and Esberitox(r). Herbal medicine might be effective for the treatment of ARS, but given the low number of clinical trials and the heterogeneous methodological quality, further research is necessary. PMID- 27404101 TI - [Task Force - "Naturheilkunde und Komplementarmedizin in medizinischen Leitlinien"]. AB - Im Rahmen der aktuellen Wissenschaftskultur stellt das Bestreben, die evidenzbasierte Naturheilkunde in die Leitlinien zu integrieren, eine besondere Herausforderung dar. In Deutschland werden medizinische Leitlinien primar von den wissenschaftlichen medizinischen Fachgesellschaften und deren Dachgesellschaft, der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF), entwickelt und verbreitet. Bisher wird das grobetae klinische Potential von Naturheilkunde und Komplementarmedizin an vielen Stellen nur unzureichend berucksichtigt. Mit der Aufnahme der Gesellschaft fur Phytotherapie (GPT) in die AWMF wurde im Jahr 2013 ein neues Kapitel in der Leitlinienarbeit der von der Rut- und Klaus-Bahlsen-Stiftung geforderten Arbeitsgruppe "Naturheilkunde und Komplementarmedizin in medizinischen Leitlinien" aufgeschlagen. Die Bestrebung, Naturheilkunde und Komplementarmedizin fester in der konventionellen medizinischen Versorgung in Deutschland zu etablieren, bekommt damit weiter Auftrieb. Durch die Forderung der Rut- und Klaus-Bahlsen Stiftung wurden die Mitarbeit oder Unterstutzung bei bisher mehr als 20 nationalen und internationalen Leitlinien, die Erstellung von 8 Cochrane-Reviews, 4 davon federfuhrend, und von 40 systematischen Reviews und Meta-Analysen in internationalen Peer-Review-Zeitschriften moglich. Erst durch die konsequente Ausweitung und Vollendung der begonnenen Arbeit wird eine Ruckentwicklung (und Ruckabwicklung) im Feld der Leitlinienarbeit unmoglich gemacht und damit die Anerkennung von Naturheilkunde und Komplementarmedizin im Facherkanon weiter gestarkt. PMID- 27404102 TI - [Haben Naturheilkunde und Komplementarmedizin einen Platz in Leitlinien des Registers der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften?]. AB - Die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) nimmt Aufgaben der inneren Zusammenarbeit, aber auch die Vertretung der medizinischen Wissenschaft nach aubetaen wahr. Die Unterstutzung der Erstellung hochwertiger Leitlinien ist ein zentrales Anliegen der AWMF, fur diese wurde mit dem Leitlinienregister ein Qualitatsmanagement entwickelt. Leitlinien als ein Instrument der Qualitatsverbesserung und -sicherung sollten versorgungsrelevante Fragestellungen aufgreifen. Dies betrifft auch Patientenpraferenzen in Bezug auf Behandlungsoptionen. Da Naturheilkunde und Komplementarmedizin in Deutschland haufig von Patienten nachgefragt und eingesetzt werden, ist die Rationale gegeben, diese in Leitlinien zu thematisieren. Allerdings besteht zunachst ein Definitionsbedarf. Naturheilkundliche und komplementarmedizinische Verfahren sollten nach gemeinsamer inhaltlicher Festlegung in Leitliniengruppen wie andere Themen behandelt werden in Bezug auf die reprasentative Gruppenzusammenstellung, Formulierung von Schlusselfragen, Recherche, Auswahl und kritische Bewertung von Studienevidenz sowie die Begrundung fur die Formulierung von Empfehlungen. Die bisherige Umsetzung in Leitlinien erscheint ausbaufahig - sowohl im Hinblick auf das Aufgreifen naturheilkundlicher und komplementarmedizinischer Themen als auch in Bezug auf deren inhaltliche Bearbeitung. Empfehlungen sind uberwiegend offen oder negativ. Es besteht ein Bedarf an Forschung zu naturheilkundlichen und komplementarmedizinischen Verfahren mit geeignetem Studiendesign; auch dies kann in Leitlinien aufgezeigt werden. PMID- 27404103 TI - [Naturheilkunde und Komplementarmedizin in medizinischen Leitlinien - eine medizinrechtliche Perspektive]. AB - Jeder Vertragsarzt ist schon konfrontiert worden mit der Diskrepanz zwischen leitliniengerechter Behandlung und Ausschlussen in der Gesetzlichen Krankenversicherung (GKV). Um der wirtschaftlichen Gefahr durch Regresse, Honorarkurzungen und Plausibilitatsprufungen zu entgehen, haben die Regeln der GKV Vorrang. Droht dann aber bei Abweichung von Leitlinien die zivilrechtliche oder gar strafrechtliche Haftung? Immer wieder fragen sich Arzte, wie verbindlich Leitlinien sind und wie weit sie die Therapiefreiheit einschranken konnen. PMID- 27404104 TI - [Naturheilkunde und Komplementarmedizin in medizinischen Leitlinien - konnen europaische Normen Leitlinien fur Naturheilkunde und Komplementarmedizin verdrangen?]. AB - Leitlinien machen in der Komplementarmedizin, wie das Beispiel der Naturheilkunde zeigt, durchaus Sinn. Sie erganzen zum Wohle des Patienten und zur besseren Orientierung des Therapeuten die bislang, auch auf europaischer Ebene, bereits bestehenden Leitlinien, die standig weiterentwickelt werden. Diese Erganzung ist dringend notwendig, weil die meisten der vorliegenden Leitlinien einzelner Fachgesellschaften die Forschungsergebnisse der Komplementarmedizin, die zum Teil beachtlich und auch evidenzbasiert sind, zum Nachteil des Patienten ignorieren. Es ist bedauerlich, dass einige Richtungen der Komplementarmedizin jedoch meinen, dass eine europaische Norm, wie sie beispielsweise Osteopathen und Homoopathen mithilfe des europaischen Normungsinstituts (CEN) durchzusetzen hoffen, sie in ihrem Kampf um Anerkennung weiterbringen wird. Der Patient, der auf eine individuelle und bestmogliche Behandlung wert legt, wird jedenfalls davon nicht profitieren. PMID- 27404105 TI - [Relevanz fur Patienten - Naturheilkunde und Komplementarmedizin in medizinischen Leitlinien]. AB - Leitlinien und Patientenleitlinien sind fur Patienten von grobetaer Bedeutung. Dies wird hier am Beispiel der chronisch entzundlichen Darmerkrankung dargestellt, wobei der Fokus auf dem Bereich Naturheilkunde und Komplementarmedizin sowie dem Wunsch der Patienten nach qualitatsgesicherten Informationen liegt. Im vorliegenden Beitrag wird auch auf die Forschung im Bereich Komplementar- und Alternativmedizin und die Unterstutzungsmoglichkeiten durch den Selbsthilfeverband Deutsche Morbus Crohn / Colitis ulcerosa Vereinigung eingegangen. PMID- 27404107 TI - [Abstract Service]. PMID- 27404106 TI - [Erratum]. PMID- 27404109 TI - Viscoelastic Properties of Extracellular Polymeric Substances Can Strongly Affect Their Washing Efficiency from Reverse Osmosis Membranes. AB - The role of the viscoelastic properties of biofouling layers in their removal from the membrane was studied. Model fouling layers of extracellular polymeric substances (EPS) originated from microbial biofilms of Pseudomonas aeruginosa PAO1 differentially expressing the Psl polysaccharide were used for controlled washing experiments of fouled RO membranes. In parallel, adsorption experiments and viscoelastic modeling of the EPS layers were conducted in a quartz crystal microbalance with dissipation (QCM-D). During the washing stage, as shear rate was elevated, significant differences in permeate flux recovery between the three different EPS layers were observed. According to the amount of organic carbon remained on the membrane after washing, the magnitude of Psl production provides elevated resistance of the EPS layer to shear stress. The highest flux recovery during the washing stage was observed for the EPS with no Psl. Psl was shown to elevate the layer's shear modulus and shear viscosity but had no effect on the EPS adhesion to the polyamide surface. We conclude that EPS retain on the membrane as a result of the layer viscoelastic properties. These results highlight an important relation between washing efficiency of fouling layers from membranes and their viscoelastic properties, in addition to their adhesion properties. PMID- 27404108 TI - Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid Inducible Gene-I. AB - Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFalpha, IFN-lambda1, and IFN-lambda2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain) were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNalpha and IFNbeta induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNalpha. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity. PMID- 27404110 TI - Patterns of Cereal Yield Growth across China from 1980 to 2010 and Their Implications for Food Production and Food Security. AB - After a remarkable 86% increase in cereal production from 1980 to 2005, recent crop yield growth in China has been slow. County level crop production data between 1980 and 2010 from eastern and middle China were used to analyze spatial and temporal patterns of rice, wheat and maize yield in five major farming systems that include around 90% of China's cereal production. Site-specific yield trends were assessed in areas where those crops have experienced increasing yield or where yields have stagnated or declined. We find that rice yields have continued to increase on over 12.3 million hectares (m. ha) or 41.8% of the rice area in China between 1980 and 2010. However, yields stagnated on 50% of the rice area (around 14.7 m. ha) over this time period. Wheat yields increased on 13.8 m. ha (58.2% of the total harvest area), but stagnated on around 3.8 m. ha (15.8% of the harvest area). Yields increased on a smaller proportion of the maize area (17.7% of harvest area, 5.3 m. ha), while yields have stagnated on over 54% (16.3 m. ha). Many parts of the lowland rice and upland intensive sub-tropical farming systems were more prone to stagnation with rice, the upland intensive sub tropical system with wheat, and maize in the temperate mixed system. Large areas where wheat yield continues to rise were found in the lowland rice and temperate mixed systems. Land and water constraints, climate variability, and other environmental limitations undermine increased crop yield and agricultural productivity in these systems and threaten future food security. Technology and policy innovations must be implemented to promote crop yields and the sustainable use of agricultural resources to maintain food security in China. In many production regions it is possible to better match the crop with input resources to raise crop yields and benefits. Investments may be especially useful to intensify production in areas where yields continue to improve. For example, increased support to maize production in southern China, where yields are still rising, seems justified. PMID- 27404112 TI - The vicinity of hyper-honeycomb beta-Li2IrO3 to a three-dimensional Kitaev spin liquid state. AB - Due to the combination of a substantial spin-orbit coupling and correlation effects, iridium oxides hold a prominent place in the search for novel quantum states of matter, including, e.g., Kitaev spin liquids and topological Weyl states. We establish the promise of the very recently synthesized hyper-honeycomb iridate beta-Li2IrO3 in this regard. A detailed theoretical analysis reveals the presence of large ferromagnetic first-neighbor Kitaev interactions, while a second-neighbor antiferromagnetic Heisenberg exchange drives the ground state from ferro to zigzag order via a three-dimensional Kitaev spin liquid and an incommensurate phase. Experiment puts the system in the latter regime but the Kitaev spin liquid is very close and reachable by a slight modification of the ratio between the second- and first-neighbor couplings, for instance via strain. PMID- 27404111 TI - Glucocorticoids Alter CRTC-CREB Signaling in Muscle Cells: Impact on PGC-1alpha Expression and Atrophy Markers. AB - Muscle wasting associated with chronic diseases has been linked to decreased expression of PGC-1alpha and overexpression of PGC-1alpha counters muscle loss. CREB, in conjunction with the CREB-regulated transcription coactivator (CRTC2), is a positive modulator of PGC-1alpha transcription. We previously reported that PGC-1alpha expression is decreased in skeletal muscle of diabetic rats despite a high level of CREB phosphorylation (i.e., activation), suggesting that CRTC2-CREB signaling may be dysregulated. In this study, the relationship between CREB/CRTC signaling and PGC-1alpha expression was examined in L6 myotubes treated with dexamethasone (Dex, 48h) to induce atrophy. Dex decreased PGC-1alpha mRNA and protein as well as the levels of CRTC1 and CRTC2 in the nucleus. Dex also altered the nuclear levels of two known regulators of CRTC2 localization; the amount of calcinuerin catalytic A subunit (CnA) was decreased whereas SIK was increased. To assess PGC-1alpha transcription, muscle cells were transfected with a PGC-1alpha luciferase reporter plasmid (PGC-1alpha-Luc). Dex suppressed PGC-1alpha luciferase activity while both isobutylmethylxanthine (IBMX) and over-expression of CRTC1 or CRTC2 increased PGC-1alpha-Luc activity. Mutation of the CRE binding site from PGC-1alpha-Luc reporter attenuated the responses to both IBMX and the CRTC proteins. Consistent with the reporter gene results, overexpression of CRTC2 produced an increase in CRTC2 in the nucleus and in PGC-1alpha mRNA and PGC 1alpha protein. Overexpression of CRTC2 was not sufficient to prevent the decrease in PGC-1alpha mRNA or protein by Dex. In summary, these data suggest that attenuated CREB/CRTC signaling contributes to the decrease in PGC-1alpha expression during atrophy. PMID- 27404113 TI - Experimental Protocol for Biodiesel Production with Isolation of Alkenones as Coproducts from Commercial Isochrysis Algal Biomass. AB - The need to replace petroleum fuels with alternatives from renewable and more environmentally sustainable sources is of growing importance. Biomass-derived biofuels have gained considerable attention in this regard, however first generation biofuels from edible crops like corn ethanol or soybean biodiesel have generally fallen out of favor. There is thus great interest in the development of methods for the production of liquid fuels from domestic and superior non-edible sources. Here we describe a detailed procedure for the production of a purified biodiesel from the marine microalgae Isochrysis. Additionally, a unique suite of lipids known as polyunsaturated long-chain alkenones are isolated in parallel as potentially valuable coproducts to offset the cost of biodiesel production. Multi kilogram quantities of Isochrysis are purchased from two commercial sources, one as a wet paste (80% water) that is first dried prior to processing, and the other a dry milled powder (95% dry). Lipids are extracted with hexanes in a Soxhlet apparatus to produce an algal oil ("hexane algal oil") containing both traditional fats (i.e., triglycerides, 46-60% w/w) and alkenones (16-25% w/w). Saponification of the triglycerides in the algal oil allows for separation of the resulting free fatty acids (FFAs) from alkenone-containing neutral lipids. FFAs are then converted to biodiesel (i.e., fatty acid methyl esters, FAMEs) by acid catalyzed esterification while alkenones are isolated and purified from the neutral lipids by crystallization. We demonstrate that biodiesel from both commercial Isochrysis biomasses have similar but not identical FAME profiles, characterized by elevated polyunsaturated fatty acid contents (approximately 40% w/w). Yields of biodiesel were consistently higher when starting from the Isochrysis wet paste (12% w/w vs. 7% w/w), which can be traced to lower amounts of hexane algal oil obtained from the powdered Isochrysis product. PMID- 27404114 TI - Characterizing the Effect of Multivalent Conjugates Composed of Abeta-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation. AB - Therapeutically active small molecules represent promising nonimmunogenic alternatives to antibodies for specifically targeting disease-relevant receptors. However, a potential drawback compared to antibody-antigen interactions may be the lower affinity of small molecules toward receptors. Here, we overcome this low-affinity problem by coating the surface of nanoparticles (NPs) with multiple ligands. Specifically, we explored the use of gold and platinum nanoparticles to increase the binding affinity of Abeta-specific small molecules to inhibit Abeta peptide aggregation into fibrils in vitro. The interactions of bare NPs, free ligands, and NP-bound ligands with Abeta are comprehensively studied via physicochemical methods (spectroscopy, microscopy, immunologic tests) and cell assays. Reduction of thioflavin T fluorescence, as an indicator for beta-sheet content, and inhibition of cellular Abeta excretion are even more effective with NP-bound ligands than with the free ligands. The results from this study may have implications in the development of therapeutics for treating Alzheimer's disease. PMID- 27404115 TI - Time-Resolved Detection of Light-Induced Dimerization of Monomeric Aureochrome-1 and Change in Affinity for DNA. AB - Aureochrome (Aureo) is a recently discovered blue light sensor protein initially from Vaucheria frigida, in which it controls blue light-dependent branch formation and/or development of a sex organ by a light-dependent change in the affinity for DNA. Although photochemical reactions of Aureo-LOV (LOV is a C terminal light-oxygen-voltage domain) and the N-terminal truncated construct containing a bZIP (N-terminal basic leucine zipper domain) and a LOV domain have previously been reported, the reaction kinetics of the change in affinity for DNA have never been elucidated. The reactions of Aureo where the cysteines are replaced by serines (AureoCS) as well as the kinetics of the change in affinity for a target DNA are investigated in the time-domain. The dimerization rate constant is obtained as 2.8 * 10(4) M(-1) s(-1), which suggests that the photoinduced dimerization occurs in the LOV domain and the bZIP domain dimerizes using the interaction with DNA. Surprisingly, binding with the target DNA is completed very quickly, 7.7 * 10(4) M(-1) s(-1), which is faster than the protein dimerization rate. It is proposed that the nonspecific electrostatic interaction, which is observed as a weak binding with DNA, may play a role in the efficient searching for the target sequence within the DNA. PMID- 27404116 TI - Next-Generation Multifunctional Electrochromic Devices. AB - The rational design and exploration of electrochromic devices will find a wide range of applications in smart windows for energy-efficient buildings, low-power displays, self-dimming rear mirrors for automobiles, electrochromic e-skins, and so on. Electrochromic devices generally consist of multilayer structures with transparent conductors, electrochromic films, ion conductors, and ion storage films. Synthetic strategies and new materials for electrochromic films and transparent conductors, comprehensive electrochemical kinetic analysis, and novel device design are areas of active study worldwide. These are believed to be the key factors that will help to significantly improve the electrochromic performance and extend their application areas. In this Account, we present our strategies to design and fabricate electrochromic devices with high performance and multifunctionality. We first describe the synthetic strategies, in which a porous tungsten oxide (WO3) film with nearly ideal optical modulation and fast switching was prepared by a pulsed electrochemical deposition method. Multiple strategies, such as sol-gel/inkjet printing methods, hydrothermal/inkjet printing methods, and a novel hybrid transparent conductor/electrochromic layer have been developed to prepare high-performance electrochromic films. We then summarize the recent advances in transparent conductors and ion conductor layers, which play critial roles in electrochromic devices. Benefiting from the developments of soft transparent conductive substrates, highly deformable electrochromic devices that are flexible, foldable, stretchable, and wearable have been achieved. These emerging devices have great potential in applications such as soft displays, electrochromic e-skins, deformable electrochromic films, and so on. We finally present a concept of multifunctional smart glass, which can change its color to dynamically adjust the daylight and solar heat input of the building or protect the users' privacy during the daytime. Energy can also be stored in the smart windows during the daytime simultaneously and be discharged for use in the evening. These results reveal that the electrochromic devices have potential applications in a wide range of areas. We hope that this Account will promote further efforts toward fundamental research on electrochromic materials and the development of new multifunctional electrochromic devices to meet the growing demands for next-generation electronic systems. PMID- 27404117 TI - Blast Quantification Using Hopkinson Pressure Bars. AB - Near-field blast load measurement presents an issue to many sensor types as they must endure very aggressive environments and be able to measure pressures up to many hundreds of megapascals. In this respect the simplicity of the Hopkinson pressure bar has a major advantage in that while the measurement end of the Hopkinson bar can endure and be exposed to harsh conditions, the strain gauge mounted to the bar can be affixed some distance away. This allows protective housings to be utilized which protect the strain gauge but do not interfere with the measurement acquisition. The use of an array of pressure bars allows the pressure-time histories at discrete known points to be measured. This article also describes the interpolation routine used to derive pressure-time histories at un-instrumented locations on the plane of interest. Currently the technique has been used to measure loading from high explosives in free air and buried shallowly in various soils. PMID- 27404120 TI - Immediate versus deferred delivery of the preterm baby with suspected fetal compromise for improving outcomes. AB - BACKGROUND: Immediate delivery of the preterm fetus with suspected compromise may decrease the risk of damage due to intrauterine hypoxia. However, it may also increase the risks of prematurity. OBJECTIVES: To assess the effects of immediate versus deferred delivery of preterm babies with suspected fetal compromise on neonatal, maternal and long-term outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing a policy of immediate delivery with deferred delivery or expectant management in preterm fetuses with suspected in utero compromise. Quasi randomised trials and trials employing a cluster-randomised design were eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included one trial of 548 women (588 babies) in the review. Women with pregnancies between 24 and 36 weeks' gestation took part. The study took place in 13 European countries, between 1993 and 2001. The difference in the median randomisation to delivery interval between immediate delivery and deferred delivery was four days (median: 0.9 (inter quartile range (IQR) 0.4 to 1.3) days for immediate delivery, median: 4.9 (IQR 2.0 to 10.8) days in the delay group).There was no clear difference in the primary outcomes of extended perinatal mortality (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.67 to 2.04, one trial, 587 babies, moderate-quality evidence) or the composite outcome of death or disability at or after two years of age (RR 1.22, 95% CI 0.85 to 1.75, one trial, 573 babies, moderate-quality evidence) with immediate delivery compared to deferred delivery. The results for these outcomes are consistent with both appreciable benefit and harm. More babies in the immediate delivery group were ventilated for more than 24 hours (RR 1.54, 95% CI 1.20 to 1.97, one trial, 576 babies). There were no differences between the immediate delivery and deferred delivery groups in any other infant mortality outcome (stillbirth, neonatal mortality, postneonatal mortality > 28 days to discharge), individual neonatal morbidity or markers of neonatal morbidity (cord pH less than 7.00, Apgar less than seven at five minutes, convulsions, interventricular haemorrhage or germinal matrix haemorrhage, necrotising enterocolitis and periventricular leucomalacia or ventriculomegaly).Some important outcomes were not reported, in particular infant admission to neonatal intensive care or special care facility, and respiratory distress syndrome. We were not able to calculate composite rates of serious neonatal morbidity, even though individual morbidities were reported, due to the risk of double counting infants with more than one morbidity.More children in the immediate delivery group had cerebral palsy at or after two years of age (RR 5.88, 95% CI 1.33 to 26.02, one trial, 507 children). There were, however, no differences in neurodevelopment impairment at or after two years (RR 1.72, 95% CI 0.86 to 3.41, one trial, 507 children), death at or after two years of age (RR 1.04, 95% CI 0.66 to 1.63, one trial, 573 children), or death or disability in childhood (six to 13 years of age) (RR 0.82, 95% CI 0.48 to 1.40, one trial, 302 children). More women in the immediate delivery group had caesarean delivery than in the deferred delivery group (RR 1.15, 95% CI 1.07 to 1.24, one trial, 547 women, high-quality evidence). Data were not available on any other maternal outcomes.There were several methodological weaknesses in the included study, and the level of evidence for the primary outcomes was graded high for caesarean section and moderate for extended perinatal mortality and death or disability at or after two years. The evidence was downgraded because the CIs for these outcomes were wide, and were consistent with both appreciable benefit and harm. Bias may have been introduced by several factors: blinding was not possible due to the nature of the intervention, data for childhood follow-up were incomplete due to attrition, and no adjustment was made in the analysis for the non-independence of babies from multiple pregnancies (39 out of 548 pregnancies). This study only included cases of suspected fetal compromise where there was uncertainty whether immediate delivery was indicated, thus results must be interpreted with caution. AUTHORS' CONCLUSIONS: Currently there is insufficient evidence on the benefits and harms of immediate delivery compared with deferred delivery in cases of suspected fetal compromise at preterm gestations to make firm recommendations. There is a lack of trials addressing this question, and limitations of the one included trial means that caution must be used in interpreting and generalising the findings. More research is needed to guide clinical practice.Although the included trial is relatively large, it has insufficient power to detect differences in neonatal mortality. It did not report any maternal outcomes other than mode of delivery, or evaluate maternal satisfaction or economic outcomes. The applicability of the findings is limited by several factors: Women with a wide range of obstetric complications and gestational ages were included, and subgroup analysis is currently limited. Advances in Doppler assessment techniques may diagnose severe compromise more accurately and help make decisions about the timing of delivery. The potential benefits of deferring delivery for longer or shorter periods cannot be presumed.Where there is uncertainty whether or not to deliver a preterm fetus with suspected fetal compromise, there seems to be no benefit to immediate delivery. Deferring delivery until test results worsen or increasing gestation favours delivery may improve the outcomes for mother and baby.There is a need for high-quality randomised controlled trials comparing immediate and deferred delivery where there is suspected fetal compromise at preterm gestations to guide clinical practice. Future trials should report all important outcomes, and should be adequately powered to detect differences in maternal and neonatal morbidity and mortality. PMID- 27404122 TI - Future Papers. PMID- 27404121 TI - Rice (Oryza sativa L.) Seed Sterilization and Germination Enhancement via Atmospheric Hybrid Nonthermal Discharge Plasma. AB - We designed a system to produce atmospheric hybrid cold-discharge plasma (HCP) based on microcorona discharge on a single dielectric barrier and applied it to inactivate microorganisms that commonly attach the rice seed husk. The cold plasma treatment modified the surface of the rice seeds, resulting in accelerated germination and enhanced water imbibition. The treatment can operate under air based ambient conditions without the need for a vacuum. The cold-plasma treatment completely inactivated pathogenic fungi and other microorganisms, enhancing the germination percentage and seedling quality. The final germination percentage of the treated rice seeds was ~98%, whereas that of the nontreated seeds was ~90%. Microcorona discharge on a single dielectric barrier provides a nonaggressive cold plasma that can be applied to organic materials without causing thermal and electrical damage. The hybrid nonthermal plasma is cost effective and consumes relatively little power, making it suitable for the surface sterilization and disinfection of organic and biological materials with large-scale compatibility. PMID- 27404123 TI - Flow Chemistry on Multigram Scale: Continuous Synthesis of Boronic Acids within 1 s. AB - The benefits and limitations of a simple continuous flow setup for handling and performing of organolithium chemistry on the multigram scale is described. The developed metalation platform embodies a valuable complement to existing methodologies, as it combines the benefits of Flash Chemistry (chemical synthesis on a time scale of <1 s) with remarkable throughput (g/min) while mitigating the risk of blockages. PMID- 27404124 TI - Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell. AB - Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. PMID- 27404125 TI - Endoplasmic reticulum-mitochondrial interaction mediated by mitofusin-1 or mitofusin-2 is not required for lipid droplet formation or adipocyte differentiation. AB - Organelles in cells physically interact with each other. Specifically, the interaction of ER and mitochondria has been shown to be important for transporting lipids between these two organelles. Lipid droplets are also closely associated with both the ER and mitochondria suggesting the interaction of ER and mitochondria may be important for triacylglycerol storage in lipid droplets. We tested the hypothesis that the efficient synthesis and storage of triacylglycerol in lipid droplets is dependent on the interaction of the ER and mitochondria using mouse embryonic fibroblasts lacking mitofusin-2 (Mfn2). Mfn2 is a GTPase that is present in mitochondrial-associated membranes (MAM) and is also present in the outer mitochondrial membrane. Mfn2 in MAM and mitochondria interact forming an interorganellar bridge. Cells lacking Mfn2 have loose ER-mitochondria contact. We found that mouse embryonic fibroblasts lacking Mfn2 have altered lipid droplet morphology. However, triacylglycerol biosynthesis was not dependent on ER-mitochondrial tethering mediated by mitofusins. Lastly, Mfn2 does not have a role in adipocyte differentiation. PMID- 27404126 TI - Comparison of three-dimensional printing and vacuum freeze-dried techniques for fabricating composite scaffolds. AB - In this study, the performances of different preparation methods of the scaffolds were analyzed for chondrocyte tissue engineering. Silk fibroin/collagen (SF/C) was fabricated using a vacuum freeze-dried technique and by 3D printing. The porosity, water absorption expansion rates, mechanical properties, and pore sizes of the resulting materials were evaluated. The proliferation and metabolism of the cells was detected at different time points using an MTT assay. Cell morphologies and distributions were observed by histological analysis and scanning electron microscopy (SEM). The porosity, water absorption expansion rate, and Young's modulus of the material obtained via 3D printing were significantly higher than those obtained by the freeze-dried method, while the pore size did not differ significantly between the two methods. MTT assay results showed that the metabolism of cells seeded on the 3D printed scaffolds was more viable than the metabolism on the freeze-dried material. H&E staining of the scaffolds revealed that the number of cells in the 3D printed scaffold was higher in comparison to a similar measurement on the freeze-dried material. Consequently, stem cells grew well inside the 3D printed scaffolds, as measured by SEM, while the internal structure of the freeze-dried scaffold was disordered. Compared with the freeze-dried technique, the 3D printed scaffold exhibited better overall performance and was more suitable for cartilage tissue engineering. PMID- 27404127 TI - GHSR deficiency suppresses neointimal formation in injured mouse arteries. AB - Growth hormone secretagogue receptor (GHSR) is involved in appetite regulation and energy homeostasis. In the present study, we examined the role of GHSR in neointimal formation following vascular injury. In the mouse model of femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in GHSR deficiency (GHSR-/-) mice compared with that in wild-type mice. Immunohistochemical staining showed that the smooth muscle cell (SMCs) in the neointima were significantly decreased in the injured arteries of GHSR-/- mice which was associated with decreased SMC proliferation and migration. Furthermore, immunoblotting demonstrated that, in cultured rat aortic SMCs, small interfering RNA-mediated GHSR knockdown suppressed the activation of Akt and ERK1/2 signaling pathway. These findings suggested a novel role of GHSR in neointimal formation likely via promoting the proliferation and migration of SMCs involving Akt and ERK1/2 signaling. Therefore, GHSR may be a potential therapeutic target in restenosis and vascular remodeling. PMID- 27404129 TI - Simultaneous Recording of Electroretinography and Visual Evoked Potentials in Anesthetized Rats. AB - The electroretinogram (ERG) and visual evoked potential (VEP) are commonly used to assess the integrity of the visual pathway. The ERG measures the electrical responses of the retina to light stimulation, while the VEP measures the corresponding functional integrity of the visual pathways from the retina to the primary visual cortex following the same light event. The ERG waveform can be broken down into components that reflect responses from different retinal neuronal and glial cell classes. The early components of the VEP waveform represent the integrity of the optic nerve and higher cortical centers. These recordings can be conducted in isolation or together, depending on the application. The methodology described in this paper allows simultaneous assessment of retinal and cortical visual evoked electrophysiology from both eyes and both hemispheres. This is a useful way to more comprehensively assess retinal function and the upstream effects that changes in retinal function can have on visual evoked cortical function. PMID- 27404128 TI - QUESPOWR MRI: QUantification of Exchange as a function of Saturation Power On the Water Resonance. AB - QUantification of Exchange as a function of Saturation Power On the Water Resonance (QUESPOWR) MRI is a new method that can estimate chemical exchange rates. This method acquires a series of OPARACHEE MRI acquisitions with a range of RF powers for the WALTZ16(*) pulse train, which are applied on the water resonance. A QUESPOWR plot can be generated from the power dependence of the % water signal, which is similar to a QUESP plot that is generated from CEST MRI acquisition methods with RF saturation applied off-resonance from water. A QUESPOWR plot can be quantitatively analyzed using linear fitting methods to provide estimates of average chemical exchange rates. Analyses of the shapes of QUESPOWR plots can also be used to estimate relative differences in average chemical exchange rates and concentrations of biomolecules. The performance of QUESPOWR MRI was assessed via simulations, an in vitro study with iopamidol, and an in vivo study with a mouse model of mammary carcinoma. The results showed that QUESPOWR MRI is especially sensitive to chemical exchange between water and biomolecules that have intermediate to fast chemical exchange rates and chemical shifts that are close to water, which are notoriously difficult to assess with other CEST MRI methods. In addition, in vivo QUESPOWR MRI detected acidic tumor tissues relative to normal tissues that are pH-neutral, and therefore may be a new paradigm for tumor detection with MRI. PMID- 27404130 TI - Enhanced optoelectronic performances of vertically aligned hexagonal boron nitride nanowalls-nanocrystalline diamond heterostructures. AB - Field electron emission (FEE) properties of vertically aligned hexagonal boron nitride nanowalls (hBNNWs) grown on Si have been markedly enhanced through the use of nitrogen doped nanocrystalline diamond (nNCD) films as an interlayer. The FEE properties of hBNNWs-nNCD heterostructures show a low turn-on field of 15.2 V/MUm, a high FEE current density of 1.48 mA/cm(2) and life-time up to a period of 248 min. These values are far superior to those for hBNNWs grown on Si substrates without the nNCD interlayer, which have a turn-on field of 46.6 V/MUm with 0.21 mA/cm(2) FEE current density and life-time of 27 min. Cross-sectional TEM investigation reveals that the utilization of the diamond interlayer circumvented the formation of amorphous boron nitride prior to the growth of hexagonal boron nitride. Moreover, incorporation of carbon in hBNNWs improves the conductivity of hBNNWs. Such a unique combination of materials results in efficient electron transport crossing nNCD-to-hBNNWs interface and inside the hBNNWs that results in enhanced field emission of electrons. The prospective application of these materials is manifested by plasma illumination measurements with lower threshold voltage (370 V) and longer life-time, authorizing the role of hBNNWs-nNCD heterostructures in the enhancement of electron emission. PMID- 27404131 TI - The molecular cloning and functional characterization of MdMYC2, a bHLH transcription factor in apple. AB - The basic helix-loop-helix (bHLH) Leu zipper transcription factor MYC2 is an important regulator in the Jasmonic acid (JA) signaling pathway. In this study, the apple MdMYC2 gene was isolated and cloned on the basis of its homology with Arabidopsis thaliana MYC2. Quantitative real time PCR (qRT-PCR) analysis demonstrated that MdMYC2 transcripts were induced by Methyl Jasmonate (MeJA) treatment and wounding. The MdMYC2 protein interacted with itself and bound the G Box motif of the AtJAZ3 gene. MdMYC2 interacted with the MdJAZ2 protein, which is a repressor protein in the JA signaling pathway. Furthermore, we obtained transgenic apple calli that either overexpressed or suppressed the MdMYC2 gene. Expression analysis with qRT-PCR demonstrated that the transcript levels of JA regulated anthocyanin biosynthetic genes, such as MdDFR, MdUF3GT, MdF3H and MdCHS, were markedly up-regulated in the MdMYC2 overexpressing calli and down regulated in the suppressing calli compared with the WT control. As a result, the overexpressing calli produced more anthocyanin, and the suppressing calli produced less. Finally, the MdMYC2 gene was ectopically expressed in Arabidopsis. Both phenotypic investigation and expression analysis demonstrated that the MdMYC2 transgenic Arabidopsis lines were more sensitive to MeJA than the WT control. Together, these results indicate that the apple MdMYC2 gene plays a vital role in the JA response. PMID- 27404132 TI - Sulphur interferes with selenium accumulation in Tartary buckwheat plants. AB - Tartary buckwheat (Fagopyrum tataricum Gaertn.) and common buckwheat (Fagopyrum esculentum Moench.) plants grown in the field were treated foliarly with 126 MUM solutions of selenate and/or sulphate in order to study the effect of sulphur (S) on selenium (Se) concentration in plants. In both species, the concentration of Se in all plant parts was similar in control and S treated plants. In Tartary buckwheat the concentration of Se was higher in S and Se treated plants than in plants treated with Se alone. S was shown to enhance Se accumulation in Tartary buckwheat. It was also shown that it is possible to produce grain and herb of Tartary and common buckwheat containing appropriate amounts of Se for food without affecting the yield of the plants. PMID- 27404133 TI - Molecular characterization of biotic and abiotic stress-responsive MAP kinase genes, IbMPK3 and IbMPK6, in sweetpotato. AB - Plants are continually exposed to numerous environmental stresses. To decrease damage caused by these potentially detrimental factors, various stress-related signaling cascades are activated in plants. One such stress-responsive signaling pathway, the mitogen-activated protein kinase (MAPK) module, plays a critical role in diverse plant stress responses. Here, we functionally characterized biotic and abiotic stress-responsive MAPK genes, IbMPK3 and IbMPK6, from sweetpotato. IbMPK3/6 contain totally 11 MAPK conserved subdomains and the phosphorylating motif TEY. Bacterially expressed IbMPK3/6 could be autophosphorylated in vitro, and these proteins phosphorylated universal kinase substrate, such as myelin basic protein. IbMPK3/6 transcripts were expressed in leaf, stem, and root of sweetpotato cultivars with storage roots of various colors. IbMPK3 and IbMPK6 were induced by various biotic/abiotic stress treatments. Furthermore, the kinase activity of IbMPK3/6 was induced during early NaCl, SA, H2O2, and ABA treatment. IbMPK3/6 were predominantly localized to the nucleus. To determine the biological functions of IbMPK3/6, we transiently expressed the IbMPK genes in tobacco (Nicotiana benthamiana) leaves, which resulted in enhanced tolerance to bacterial pathogen and increased expression of pathogenesis-related (PR) genes. These data demonstrate that IbMPK3 and IbMPK6 play significant roles in plant responses to environmental stress. PMID- 27404135 TI - Expression of a repressor form of the Arabidopsis thaliana transcription factor TCP16 induces the formation of ectopic meristems. AB - Plants that express a fusion of the Arabidopsis thaliana class I TCP transcription factor TCP16 to the EAR repressor domain develop several phenotypic alterations, including rounder leaves, short petioles and pedicels, and delayed elongation of sepals, petals and anthers. In addition, these plants develop lobed cotyledons and ectopic meristems. Ectopic meristems are formed on the adaxial side of cotyledon petioles and arise from a cleft that is formed at this site. Analysis of the expression of reporter genes indicated that meristem genes are reactivated at the site of emergence of ectopic meristems, located near the bifurcation of cotyledon veins. The plants also show increased transcript levels of the boundary-specific CUP-SHAPED COTYLEDON (CUC) genes. The results suggest that TCP16 is able to modulate the induction of meristematic programs and the differentiation state of plant cells. PMID- 27404134 TI - Magnesium decreases leaf scald symptoms on rice leaves and preserves their photosynthetic performance. AB - The aim of this study was to investigate the effect of magnesium (Mg) on the photosynthetic gas exchange parameters ([net CO2 assimilation rate (A), stomatal conductance (gs), and internal CO2 concentration (Ci)], chlorophyll (Chl) fluorescence a parameters {minimal fluorescence (F0), maximum fluorescence (Fm), maximum quantum yield of photosystem II (Fv/Fm), photochemical quenching coefficient (qp), yield of photochemistry [Y(II)], yield of regulated energy dissipation [Y(NPQ)] and yield of non-regulated dissipation losses [Y(NO)]} as well as on the concentrations of chloroplastidic pigments in rice plants grown in a nutrient solution containing 0.5 or 1.5 mM of Mg (-Mg or + Mg plants, respectively) and non-inoculated or inoculated with Monographella albescens. A higher Mg supply decreased the leaf scald symptoms in addition to partially preserving the photosynthetic performance of rice leaves challenged with M. albescens. Photosynthetic impairments were associated with photochemical and biochemical dysfunctions at the chloroplast level. The images of Chl a fluorescence evidenced increases in both the Y(II) and qp coupled with decreases in Y(NPQ) associated with a higher Mg supply regardless of inoculation, suggesting increased electron transport rates and lower energy dissipation as heat. Notably, as the leaf scald developed, the use of light energy through photochemical reactions was continuously lost, especially for the inoculated -Mg plants. Interestingly, the lower values for F0, Fm, and Fv/Fm for -Mg plants were associated with greater photochemical dysfunctions and a progressive loss of photosynthetic pigments during the infection process of M. albescens. The underlying mechanism through which Mg can affect rice resistance against M. albescens remains to be fully elucidated. PMID- 27404136 TI - Follow-up after acute poisoning by substances of abuse: a prospective observational cohort study. AB - OBJECTIVE: To chart follow-up of patients after acute poisoning by substances of abuse, register whether patients referred to specialist health services attended, and whether patients contacted a general practitioner (GP) after the poisoning episode. DESIGN: Observational cohort study. SETTING: A primary care emergency outpatient clinic in Oslo, Norway. SUBJECTS: Patients >=12 years treated for acute poisoning by substances of abuse were included consecutively from October 2011 to September 2012. MAIN OUTCOME MEASURES: Follow-up initiated at discharge, proportion of cases in which referred patients attended within three months, and proportion of cases in which the patient consulted a GP the first month following discharge. RESULTS: There were 2343 episodes of acute poisoning by substances of abuse. In 391 (17%) cases the patient was hospitalised, including 49 (2%) in psychiatric wards. In 235 (10%) cases the patient was referred to specialist health services, in 91 (4%) advised to see their GP, in 82 (3%) to contact social services, in 74 (3%) allotted place in a homeless shelter, and in 93 (4%) other follow-up was initiated. In 1096 (47%) cases, the patient was discharged without follow-up, and in a further 324 (14%), the patient self-discharged. When referred to specialist health services, in 200/235 (85%) cases the patient attended within three months. Among all discharges, in 527/1952 (27%) cases the patient consulted a GP within one month. When advised to see their GP, in 45/91 (49%) cases the patient did. CONCLUSION: Attendance was high for follow-up initiated after acute poisoning by substances of abuse. KEY POINTS Despite poor long-term prognosis, patients treated for acute poisoning by substances of abuse are frequently not referred to follow-up. Nearly all patients referred to specialist health services attended, indicating the acute poisoning as an opportune moment for intervention. Advising patients to contact their GP was significantly associated with patients consulting the GP, but few patients were so advised. One out of three patients was discharged without follow-up, and there seems to be an unused potential for GP involvement. PMID- 27404138 TI - Scanning sports. PMID- 27404137 TI - Reproductive endocrinology: Contraceptives, exercise and diet - are all three needed in PCOS? PMID- 27404140 TI - Noteworthy. PMID- 27404144 TI - The World Is My Schoolroom. PMID- 27404147 TI - Rehabilitation of Football Players With Lumbar Spine Injury (Part 1 of 2). AB - In brief: Rehabilitation of football players with low back pain caused by injury is a comprehensive process. Accurate diagnosis followed by early intervention is necessary. The rehabilitation plan can be divided into two phases: the pain control phase, discussed in this article, and the training phase, to be discussed in part 2 in a coming issue. The pain-control phase may include a variety of passive modalities, flexion or extension exercises, lumbar mobilization, traction, and selective (precise localization with precise center) injections. The author stresses the importance of understanding the anatomy and biomechanics of the lumbar spine, referred pain and potential pain generators, the stages of the degenerative process, and lumbar spine injuries when planning a rehabilitation program. PMID- 27404141 TI - Sportsmedicine forum. AB - A Forum For Our Readers Sportsmedicine Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Sportsmedicine Forum, THE PHYSICIAN AND SPORTSMEDICINE, 4530 W 77th St, Minneapolis, MN 55435. PMID- 27404148 TI - Cardiac Rehabilitation: Then and Now. AB - In brief: Cardiac rehabilitation, born of cardiology in order to care for patients with coronary heart disease, has evolved into an accepted area of clinical practice. As more and more patients survive a coronary event, the need for state-of-the-art methods of rehabilitation will be increasingly needed. The author reviews the history of cardiac rehabilitation, discusses its current status, and predicts What courses of action will be needed as the field continues to evolve. PMID- 27404149 TI - Factors Associated With Collapse During and After Ultramarathon Footraces: A Preliminary Study. AB - In brief: In a preliminary study to evaluate possible causes of exhaustion, 48 runners who collapsed during or after an ultramarathon race were questioned about their training methods. The training profiles were compared with those of matched controls who had finished the same race without collapsing. Possible contributing factors found among the collapsed runners included inadequate training, failing to carbohydrate load, not eating a prerace breakfast, prerace illness, and hypothermia (during one race, which was run in cold, wet, windy conditions). The authors suggest that regardless of athletic ability or previous racing experience, runners may be prone to collapse during or after ultramarathon races if their prerace training and preparation are inadequate. PMID- 27404150 TI - Effects of a Mandatory Health Screening and Physical Maintenance Program for Law Enforcement Officers. AB - In brief: High-risk, physically demanding occupations such as police work are associated with high medical costs. The potential economic benefits of health assessment, disease prevention, and performance testing Programs, in contrast to post hoc remedial Programs, have seldom been evaluated. This article presents the effects of such a program on 4,480 California Highway Patrol officers who were tested every six months over an 18month period. Mean systolic blood pressure and resting heart rate decreased significantly, and the proportion of officers who passed an ergometer test simulating job demands increased from 59.2% to 76.3%. Medical referrals and health-related changes in Job status decreased during the program. On-the-job injuries and cardiovascular events, which previously had been increasing, also declined. PMID- 27404151 TI - How I Manage Turf Toe. AB - In brief: Jamming or forced hyperextension of the hallux at the metatarsophalangeal (MP) joint in athletes can produce a painful condition known as turf toe. To treat this problem, the author recommends restriction of motion, ice, a compression dressing, and elevation. Taping the hallux restricts hyperextension of the MP joint. Rehabilitation consists of exercises done at home, and in some cases, whirlpool and ultrasound treatments. The author also offers advice about the type of shoe that athletes should wear to avoid turf toe, and discusses the differences between natural and artificial turf as they relate to turf toe. PMID- 27404152 TI - Medical Coverage of High School Football in New York State. AB - In brief: The principals of all New York secondary schools were surveyed regarding medical coverage of interscholastic sports. The overall response rate was 65.3%, which represents approximately 90% of schools having varsity football teams. Results showed that the team physicians for most of the high schools are family practice physicians. Medical coverage at football games is often not provided directly by a physician, especially at the junior varsity and freshman levels. In addition, many schools do not record injury data, and only about half require either parental liability waivers or health insurance. One fourth of the high schools have been involved in litigation related to sports injuries in the past five years. The authors suggest several ways to correct these problems, measures that could apply to other states as well. PMID- 27404153 TI - Acute Ulnar Collateral Ligament Injury in a Baseball Pitcher. AB - A group of experts discussed a case from the American Sports Medicine Institute in Birmingham, Alabama. This case conference is part of a series featuring a variety of sports medicine topics. PMID- 27404154 TI - Pathogenic Weight-Control Behaviors of Female College Gymnasts. AB - In brief: To study the methods and extent to which iemale college gymnasts diet, data were collected from 42 gymnasts aged 17 to 22 years, who represented five teams in a major athletic conference. The survey showed that (1) all the participants were dieting; (2) 26 were using at least one form of pathogenic weight-control behavior; and (3) 21 of the 28 competitors who were told by their coaches that they were too heavy resorted to using pathogenic weight-control behaviors. The authors discuss the implications of the demands of gymnastics and the additional social pressure to maintain exceptional thinness. PMID- 27404156 TI - Fitness and Exercise Issues for Black Americans. PMID- 27404155 TI - Striving for Safe, Healthy, and Fair Summer Olympic Games. PMID- 27404158 TI - Prescribing Exercise to Black Americans. AB - Recent research on the causes of hypertension could influence the care given by sports medicine physicians to black patients in general, and to black athletes in particular. PMID- 27404157 TI - Can Exercise Help Treat Hypertension in Black Americans? AB - Hypertension is more prevalent among black Americans than among white Americans. In recognition of this fact, some physicians are devising outreach programs that inexpensively promote improved health habits, including exercise, in black communities. PMID- 27404159 TI - Sports Medicine Meets Minority Medicine. AB - The sports medicine community is beginning to address the fitness and exercise needs of the black community-and to encourage more blacks to join its ranks. PMID- 27404160 TI - The Team Physician Is a Sideline Psychologist. AB - Being a team physician requires much more than being a good clinician, says the author. It requires understanding the psychology of the players, the coach, and the team as a whole. PMID- 27404161 TI - Checking Your Pulse Rate. PMID- 27404163 TI - Intracerebral Hemorrhages From Cerebral Arteriovenous Malformations: Prognostic Grading. PMID- 27404164 TI - Burn Injuries and Their Impact on Cognitive-Communication Skills in the Inpatient Rehabilitation Setting. AB - The prevalence and extent of cognitive-communication disorders and factors that have impact on outcomes are examined in the burn population within an inpatient rehabilitation facility. A retrospective data analysis was conducted on adults diagnosed with burn injury (n = 144). Descriptive statistics were used to identify the prevalence of cognitive-communication deficits on admission and discharge. The main outcomes were cognitive-communication ratings on discharge from inpatient rehabilitation as measured by the memory and problem-solving domains of the Functional Independence Measure (FIM) and composite score of the Functional Communication Measure (FCM). Medical, demographic and rehabilitation predictors of the main outcomes were assessed using regression analyses. On admission to inpatient rehabilitation, 79% of the total population presented with cognitive-communication impairments, and of them, 27% presented with persistent deficits on discharge. Admission FIM memory score, marital status, and age were significant predictors of discharge FIM memory score. Admission FIM problem solving score, age, marital status, and prehospital living-with were significant predictors of discharge FIM problem-solving score. Admission FCM score and age were significant predictors of discharge FCM cognitive score. Persons with burn injuries are at risk for cognitive-communication impairments, which may persist after inpatient rehabilitation. FIM data obtained on admission can be used as a screening tool to identify these at-risk patients. Future work is needed to assess the efficacy of speech-language pathologist intervention for cognitive communication deficits within the burn injury population. PMID- 27404165 TI - Randomized, Paired-Site Comparison of Autologous Engineered Skin Substitutes and Split-Thickness Skin Graft for Closure of Extensive, Full-Thickness Burns. AB - Stable closure of full-thickness burn wounds remains a limitation to recovery from burns of greater than 50% of the total body surface area (TBSA). Hypothetically, engineered skin substitutes (ESS) consisting of autologous keratinocytes and fibroblasts attached to collagen-based scaffolds may reduce requirements for donor skin, and decrease mortality. ESS were prepared from split thickness skin biopsies collected after enrollment of 16 pediatric burn patients into an approved study protocol. ESS and split-thickness autograft (AG) were applied to 15 subjects with full-thickness burns involving a mean of 76.9% TBSA. Data consisted of photographs, tracings of donor skin and healed wounds, comparison of mortality with the National Burn Repository, correlation of TBSA closed wounds with TBSA full-thickness burn, frequencies of regrafting, and immunoreactivity to the biopolymer scaffold. One subject expired before ESS application, and 15 subjects received 2056 ESS grafts. The ratio of closed wound to donor areas was 108.7 +/- 9.7 for ESS compared with a maximum of 4.0 +/- 0.0 for AG. Mortality for enrolled subjects was 6.25%, and 30.3% for a comparable population from the National Burn Repository (P < .05). Engraftment was 83.5 +/- 2.0% for ESS and 96.5 +/- 0.9% for AG. Percentage TBSA closed was 29.9 +/- 3.3% for ESS, and 47.0 +/- 2.0% for AG. These values were significantly different between the graft types. Correlation of % TBSA closed with ESS with % TBSA full thickness burn generated an R value of 0.65 (P < .001). These results indicate that autologous ESS reduce mortality and requirements for donor skin harvesting, for grafting of full-thickness burns of greater than 50% TBSA. PMID- 27404169 TI - The Porch: Philip Guston. PMID- 27404166 TI - Burn Injury Has Skeletal Site-Specific Effects on Bone Integrity and Markers of Bone Remodeling. AB - To further understand the mechanisms of perturbations in bone remodeling following severe burn injury, the biomechanical properties, genetic expression, and serological markers were evaluated in rodents at six time intervals within 6 weeks following injury. Moreover, these effects were observed in rodent tibia and lumbar vertebrae to explore possible skeletal site localization of this pathologic bone loss. Rodents underwent either thermal injury (100 degrees C water, 30 seconds, 30% BSA) or sham burn. Bone mineral density was evaluated though peripheral quantitative computer tomography, and specialized apparatus measured the weight bearing capacity of tibia and lumbar vertebrae. Markers of bone resorption (RANK ligand, osteocalcin) and bone formation (osteoprotegerin, procollagenase type 1 alpha 2) were measured at 7, 14, and 21 days following injury, and serum RANK-ligand levels were observed at these time intervals. Rodent body mass, bone mineral density, and weight bearing capacity were negatively influenced both acutely and several weeks following burn injury. Moreover, a genetic expression profile favoring increased bone resorption and lower bone formation was demonstrated. Our serum analysis findings of significantly increased RANKL 1 and 2 weeks following injury support the increased expression of bone resorption markers. Furthermore, these effects occurred sooner and were more pronounced in the rodent lumbar vertebrae than tibia. These results suggest that severe burn injury results in perturbations in bone remodeling secondary to increased bone resorption and diminished bone formation, impacting both bone mineral density and weight bearing capacity. Furthermore, these processes had a skeletal site effect more pronounced in the lumbar vertebrae. With a better understanding of the mechanisms of burn-injury bone loss, targeted therapies can be implemented to improve long-term clinical outcomes. PMID- 27404170 TI - HIV and Transplantation: New Reasons for HOPE. PMID- 27404178 TI - An HIV Vaccine: Mapping Uncharted Territory. PMID- 27404179 TI - Marking Time in the Global HIV/AIDS Pandemic. PMID- 27404180 TI - A PIECE OF MY MIND. A Hand to Hold. PMID- 27404181 TI - Condomless Sex With Virologically Suppressed HIV-Infected Individuals: How Safe Is It? PMID- 27404182 TI - Antiretrovirals for HIV Treatment and Prevention: The Challenges of Success. PMID- 27404183 TI - Visions for an AIDS-Free Generation: Red Ribbons of Hope. PMID- 27404184 TI - Effect of Patient Navigation With or Without Financial Incentives on Viral Suppression Among Hospitalized Patients With HIV Infection and Substance Use: A Randomized Clinical Trial. AB - IMPORTANCE: Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes. Patient navigation (care coordination with case management) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care, but there is little evidence for their efficacy in improving HIV-1 viral suppression rates. OBJECTIVE: To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital inpatients. DESIGN, SETTING, AND PARTICIPANTS: From July 2012 through January 2014, 801 patients with HIV infection and substance use from 11 hospitals across the United States were randomly assigned to receive patient navigation alone (n = 266), patient navigation plus financial incentives (n = 271), or treatment as usual (n = 264). HIV-1 plasma viral load was measured at baseline and at 6 and 12 months. INTERVENTIONS: Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months. Financial incentives (up to $1160) were provided for achieving targeted behaviors aimed at reducing substance use, increasing engagement in HIV care, and improving HIV outcomes. Treatment as usual was the standard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was HIV viral suppression (<=200 copies/mL) relative to viral nonsuppression or death at the 12 month follow-up. RESULTS: Of 801 patients randomized, 261 (32.6%) were women (mean [SD] age, 44.6 years [10.0 years]). There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months. Eighty-five of 249 patients (34.1%) in the usual-treatment group experienced treatment success compared with 89 of 249 patients (35.7%) in the navigation-only group for a treatment difference of 1.6% (95% CI, -6.8% to 10.0%; P = .80) and compared with 98 of 254 patients (38.6%) in the navigation-plus incentives group for a treatment difference of 4.5% (95% CI -4.0% to 12.8%; P = .68). The treatment difference between the navigation-only and the navigation plus-incentives group was -2.8% (95% CI, -11.3% to 5.6%; P = .68). CONCLUSIONS AND RELEVANCE: Among hospitalized patients with HIV infection and substance use, patient navigation with or without financial incentives did not have a beneficial effect on HIV viral suppression relative to nonsuppression or death at 12 months vs treatment as usual. These findings do not support these interventions in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01612169. PMID- 27404186 TI - Association of Medical Male Circumcision and Antiretroviral Therapy Scale-up With Community HIV Incidence in Rakai, Uganda. AB - IMPORTANCE: Medical male circumcision (MMC) and antiretroviral therapy (ART) are proven HIV prevention interventions, but there are limited data on the population level effect of scale-up of these interventions in sub-Saharan Africa. Such evaluation is important for planning and resource allocation. OBJECTIVE: To examine whether increasing community MMC and ART coverage was associated with reduced community HIV incidence in Rakai District, Uganda. DESIGN, SETTING, AND PARTICIPANTS: Using person-level data from population-based surveys conducted from 1999 through 2013 in 45 rural Rakai communities, community-level ART and MMC coverage, sociodemographics, sexual behaviors, and HIV prevalence and incidence were estimated in 3 periods: prior to the availability of ART and MMC (1999 2004), during early availability of ART and MMC (2004-2007), and during mature program scale-up (2007-2013). EXPOSURES: Community MMC coverage in males and ART coverage in HIV-positive persons of the opposite sex based on self-reported MMC status and ART use. MAIN OUTCOMES AND MEASURES: Adjusted incidence rate ratios (IRRs) for sex-specific community HIV incidence estimated using multivariable Poisson regression with generalized estimating equations. RESULTS: From 1999 through 2013, 44,688 persons participated in 1 or more surveys (mean age at the first survey, 24.6 years [range, 15-49]; female, 56.5%; mean survey participation rate, 92.6% [95% CI, 92.4%-92.7%]). Median community MMC coverage increased from 19% to 39%, and median community ART coverage rose from 0% to 21% in males and from 0% to 26% in females. Median community HIV incidence declined from 1.25 to 0.84 per 100 person-years in males, and from 1.25 to 0.99 per 100 person-years in females. Among males, each 10% increase in community MMC coverage was associated with an adjusted IRR of 0.87 (95% CI, 0.82-0.93). Comparing communities with MMC coverage more than 40% (mean male community incidence, 1.03 per 100 person-years) with communities with coverage of 10% or less (mean male incidence, 1.69 per 100 person-years), the adjusted IRR was 0.61 (95% CI, 0.43-0.88). For each 10% increase in female self-reported ART coverage, there was no significant reduction in male HIV incidence (adjusted IRR, 0.95 [95% CI, 0.81-1.13]). Comparing communities with female ART coverage more than 20% (mean male incidence, 0.87 per 100 person-years) to communities with female ART coverage of 20% or less (mean male incidence, 1.17 per 100 person-years), the adjusted IRR was 0.77 (95% CI, 0.61-0.98). Neither MMC nor male ART coverage was associated with lower female community HIV incidence. CONCLUSIONS AND RELEVANCE: In Rakai, Uganda, increasing community MMC and female ART coverage was associated with lower community HIV incidence in males. If similar associations are found elsewhere, this would support further scale-up of MMC and ART for HIV prevention in sub-Saharan Africa. PMID- 27404188 TI - Reaching High-Risk Patients for HIV Preexposure Prophylaxis. PMID- 27404185 TI - Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. AB - IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. DESIGN, SETTING, AND PARTICIPANTS: The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. EXPOSURES: Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. MAIN OUTCOMES AND MEASURES: Risk of within-couple HIV transmission to the HIV-negative partner. RESULTS: Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35 48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. CONCLUSIONS AND RELEVANCE: Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk. PMID- 27404189 TI - HIV Screening. PMID- 27404190 TI - Genvoya: A New 4-Drug Combination for HIV. PMID- 27404191 TI - Trends in Caregiving Assistance for Home-Dwelling, Functionally Impaired Older Adults in the United States, 1998-2012. PMID- 27404187 TI - Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel. AB - IMPORTANCE: New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE: To provide updated recommendations for the use of antiretroviral therapy in adults (aged >=18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW: A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS: Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. CONCLUSIONS AND RELEVANCE: Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults. PMID- 27404192 TI - Management of Community-Acquired Pneumonia. PMID- 27404193 TI - Management of Community-Acquired Pneumonia. PMID- 27404194 TI - Management of Community-Acquired Pneumonia. PMID- 27404195 TI - Management of Community-Acquired Pneumonia--Reply. PMID- 27404196 TI - Hospitalization After a Return Visit to the Emergency Department. PMID- 27404197 TI - Hospitalization After a Return Visit to the Emergency Department--Reply. PMID- 27404198 TI - US Dietary Recommendations. PMID- 27404199 TI - US Dietary Recommendations. PMID- 27404200 TI - US Dietary Recommendations--Reply. PMID- 27404201 TI - Vaccine Pricing and US Immunization Policies. PMID- 27404202 TI - Vaccine Pricing and US Immunization Policies--Reply. PMID- 27404204 TI - The Acquired Immune Deficiency Syndrome: The Ever-Broadening Clinical Spectrum. PMID- 27404205 TI - JAMA PATIENT PAGE. Human Immunodeficiency Virus. PMID- 27404206 TI - Experience implementing distress screening using the National Comprehensive Cancer Network distress thermometer at an urban safety-net hospital. PMID- 27404207 TI - Retracing the in vivo haematopoietic tree using single-cell methods. AB - The dynamic process by which self-renewing stem cells and their offspring proliferate and differentiate to create the erythroid, myeloid and lymphoid lineages of the blood system has long since been an important topic of study. A range of recent single cell and family tracing methodologies such as massively parallel single-cell RNA-sequencing, mass cytometry, integration site barcoding, cellular barcoding and transposon barcoding are enabling unprecedented analysis, dissection and re-evaluation of the haematopoietic tree. In addition to the substantial experimental advances, these new techniques have required significant theoretical development in order to make biological deductions from their data. Here, we review these approaches from both an experimental and inferential point of view, considering their discoveries to date, their capabilities, limitations and opportunities for further development. PMID- 27404208 TI - Prevalence of asymptomatic heart failure in formerly pre-eclamptic women: a cohort study. AB - OBJECTIVES: After pre-eclampsia (PE), the prevalence of structural heart disease without symptoms, i.e. heart failure Stage B (HF-B), may be as high as one in four women in the first year postpartum. We hypothesize that a significant number of formerly pre-eclamptic women with HF-B postpartum are still in their resolving period and will not have HF-B during follow-up. METHODS: In this prospective longitudinal cohort study, we included 69 formerly pre-eclamptic women who underwent serial echocardiographic measurements at 1 and 4 years postpartum. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi <= 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Women were subdivided and analyzed according to HF-B outcome: no HF-B at either visit; HF-B at first visit only; HF B at second visit only; HF-B at both visits. RESULTS: The prevalence of HF-B in formerly pre-eclamptic women was 23% in the first year postpartum and 23% after 4 years. At the second visit, HF-B had resolved in 62.5% of affected women but was newly developed in 19% of initially unaffected women. At the first visit, 56% of women diagnosed with HF-B had reduced systolic function whereas at the second visit 69% of women with HF-B had concentric remodeling with mostly normal ejection fraction, consistent with diastolic dysfunction. CONCLUSIONS: The prevalence of HF-B can be considered consistently high (1 in 4) amongst formerly pre-eclamptic women at follow-up. Nonetheless, at an individual level, more than 60% of women found initially to be affected by HF-B will recover, whilst about 20% of formerly pre-eclamptic women with normal echocardiography in the first year postpartum will develop HF-B over the following years. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27404209 TI - On extinction time of a generalized endemic chain-binomial model. AB - We considered a chain-binomial epidemic model not conferring immunity after infection. Mean field dynamics of the model has been analyzed and conditions for the existence of a stable endemic equilibrium are determined. The behavior of the chain-binomial process is probabilistically linked to the mean field equation. As a result of this link, we were able to show that the mean extinction time of the epidemic increases at least exponentially as the population size grows. We also present simulation results for the process to validate our analytical findings. PMID- 27404210 TI - Aggregation is the key to succeed in random walks. AB - In a random walk (RW) in Z an individual starts at 0 and moves at discrete unitary steps to the right or left with respective probabilities p and 1-p. Assuming p > 1/2 and finite a, a > 1, the probability that state a will be reached before -a is Q(a, p) where Q(a, p) > p. Here we introduce the cooperative random walk (CRW) involving two individuals that move independently according to a RW each but dedicate a fraction of time theta to approach the other one unit. This simple strategy seems to be effective in increasing the expected number of individuals arriving to a first. We conjecture that this is a possible underlying mechanism for efficient animal migration under noisy conditions. PMID- 27404211 TI - Epidemics on networks with heterogeneous population and stochastic infection rates. AB - In this paper we study the diffusion of an SIS-type epidemics on a network under the presence of a random environment, that enters in the definition of the infection rates of the nodes. Accordingly, we model the infection rates in the form of independent stochastic processes. To analyze the problem, we apply a mean field approximation, which allows to get a stochastic differential equations for the probability of infection in each node, and classical tools about stability, which require to find suitable Lyapunov's functions. Here, we find conditions which guarantee, respectively, extinction and stochastic persistence of the epidemics. We show that there exists two regions, given in terms of the coefficients of the model, one where the system goes to extinction almost surely, and the other where it is stochastic permanent. These two regions are, unfortunately, not adjacent, as there is a gap between them, whose extension depends on the specific level of noise. In this last region, we perform numerical analysis to suggest the true behavior of the solution. PMID- 27404212 TI - Optimized volume models of earthquake-triggered landslides. AB - In this study, we proposed three optimized models for calculating the total volume of landslides triggered by the 2008 Wenchuan, China Mw 7.9 earthquake. First, we calculated the volume of each deposit of 1,415 landslides triggered by the quake based on pre- and post-quake DEMs in 20 m resolution. The samples were used to fit the conventional landslide "volume-area" power law relationship and the 3 optimized models we proposed, respectively. Two data fitting methods, i.e. log-transformed-based linear and original data-based nonlinear least square, were employed to the 4 models. Results show that original data-based nonlinear least square combining with an optimized model considering length, width, height, lithology, slope, peak ground acceleration, and slope aspect shows the best performance. This model was subsequently applied to the database of landslides triggered by the quake except for two largest ones with known volumes. It indicates that the total volume of the 196,007 landslides is about 1.2 * 10(10) m(3) in deposit materials and 1 * 10(10) m(3) in source areas, respectively. The result from the relationship of quake magnitude and entire landslide volume related to individual earthquake is much less than that from this study, which reminds us the necessity to update the power-law relationship. PMID- 27404214 TI - ATLAS of Biochemistry: A Repository of All Possible Biochemical Reactions for Synthetic Biology and Metabolic Engineering Studies. AB - Because the complexity of metabolism cannot be intuitively understood or analyzed, computational methods are indispensable for studying biochemistry and deepening our understanding of cellular metabolism to promote new discoveries. We used the computational framework BNICE.ch along with cheminformatic tools to assemble the whole theoretical reactome from the known metabolome through expansion of the known biochemistry presented in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We constructed the ATLAS of Biochemistry, a database of all theoretical biochemical reactions based on known biochemical principles and compounds. ATLAS includes more than 130 000 hypothetical enzymatic reactions that connect two or more KEGG metabolites through novel enzymatic reactions that have never been reported to occur in living organisms. Moreover, ATLAS reactions integrate 42% of KEGG metabolites that are not currently present in any KEGG reaction into one or more novel enzymatic reactions. The generated repository of information is organized in a Web-based database ( http://lcsb databases.epfl.ch/atlas/ ) that allows the user to search for all possible routes from any substrate compound to any product. The resulting pathways involve known and novel enzymatic steps that may indicate unidentified enzymatic activities and provide potential targets for protein engineering. Our approach of introducing novel biochemistry into pathway design and associated databases will be important for synthetic biology and metabolic engineering. PMID- 27404215 TI - Imaging of Spine Trauma. AB - : : Imaging with computed tomography and magnetic resonance imaging is fundamental to the evaluation of traumatic spinal injury. Specifically, neuroradiologic techniques show the exact location of injury, evaluate the stability of the spine, and determine neural element compromise. This review focuses on the complementary role of different radiologic modalities in the diagnosis of patients with traumatic injuries of the spine. The role of imaging in spinal trauma classifications will be addressed. The importance of magnetic resonance imaging in the assessment of soft tissue injury, particularly of the spinal cord, will be discussed. Last, the increasing role of advanced imaging techniques for prognostication of the traumatic spine will be explored. ABBREVIATIONS: ADC, apparent diffusion coefficientALL, anterior longitudinal ligamentAS, ankylosing spondylitisASIA, American Spine Injury AssociationCTA, computed tomography angiographyCVJ, craniovertebral junctionDISH, diffuse idiopathic skeletal hyperostosisDTI, diffusion tensor imagingFA, fractional anisotropyMDCT, multidetector computed tomographyMRA, magnetic resonance angiographySCI, spinal cord injurySTIR, short tau inversion recoveryVAI, vertebral artery injury. PMID- 27404213 TI - Epidemiology of Vasopressin Use for Adults with Septic Shock. AB - RATIONALE: Vasopressin may be used to treat vasodilatory hypotension in septic shock, but it is not recommended by guidelines as a first- or second-line agent. Little is known about how often the drug is used currently in septic shock. OBJECTIVES: We conducted this study to describe patterns of vasopressin use in a large cohort of U.S. adults with septic shock and to identify patient and hospital characteristics associated with vasopressin use. METHODS: This was a retrospective cohort study of adults admitted to U.S. hospitals with septic shock in the Premier healthcare database (July 2008 to June 2013). We performed multilevel mixed-effects logistic regression with hospitals as a random effect to identify factors associated with use of vasopressin alone or in combination with other vasopressors on at least 1 day of hospital admission. We calculated quotients of Akaike Information Criteria (AIC) to determine relative contributions of patient and hospital characteristics to observed variation. MEASUREMENTS AND MAIN RESULTS: Among 584,421 patients with septic shock in 532 hospitals, 100,923 (17.2%) received vasopressin. A total of 6.1% of patients receiving vasopressin received vasopressin alone, and 93.9% received vasopressin in combination with other vasopressors (up to five vasopressors in 15 different combinations). The mean monthly rate of vasopressin use increased from 14.5 to 19.6% over the study period, representing an average annual relative increase of 8% (P < 0.001). The median hospital rate of vasopressin use for septic shock was 11.7% (range, 0-69.7%). Patient demographic and clinical characteristics, including patient age (adjusted odds ratio, 0.71 for age > 85 yr compared with the reference group of age < 50 yr; 95% confidence interval, 0.69-0.74) and acute respiratory dysfunction (adjusted odds ratio, 3.25; 95% confidence interval, 3.20 3.31), were responsible for the majority of observed variation in vasopressin use (quotient of AICs, 0.56). However, hospital of admission also contributed substantially to observed variation (quotient of AICs, 0.37). CONCLUSIONS: Approximately one-fifth of patients with septic shock received vasopressin, but rarely as a single vasopressor. The use of vasopressin has increased over time. The likelihood of receiving vasopressin was strongly associated with the specific hospital to which each patient was admitted. PMID- 27404216 TI - Vimentin as a Marker of Early Differentiating, Highly Motile Corneal Epithelial Cells. AB - Vimentin (Vim), a cytoskeletal intermediate filament, is part of a naturally occurring reversible program, the Epithelial-Mesenchymal Transition (EMT), which converts epithelial cells into mesenchymal-like derivatives. Based on previous results showing that epithelial cells co-express Vim and keratin (Krt) as part of a cytoskeletal network which confers them a highly motile phenotype, we explored the role of Vim in rabbit corneal epithelial cells or RCE1(5T5) cells, an established model of corneal epithelial differentiation. Vim and keratin filaments were co-expressed in cells localized at the proliferative/migratory rim of the growing colonies, but not in basal cells from the center of the colonies nor at suprabasal cell layers. Flow cytometry and qPCR demonstrated that there was a decrease in Krt+ /Vim+ cell number and DeltaNp63alpha expression when cells reached confluence and formed a 4-5 layered epithelium, while there was a concomitant increase of both Pax-6 expression and Krt+ /Vim- cells. Inhibition of cell proliferation with mitomycin C did not modify cell motility nor the expression of Vim. We studied the distribution and expression of alpha6 integrin, a protein also involved in cell migration. The results demonstrated that alpha6 integrin had a distribution which was, in part, co-linear with Vim at the proliferative/migratory rim of cell colonies, suggesting an indirect interaction between these proteins. Immunoprecipitation and immunostaining assays indicated that plectin might be mediating such interaction. These data suggest that Vim expression in corneal epithelium is found in a cell population composed of highly motile cells with a Vim+ /Krt+ /DeltaNp63alpha+ /Pax-6low /alpha6 integrin+ phenotype. J. Cell. Physiol. 232: 818-830, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27404217 TI - Maghemite nanoparticle-decorated hollow fiber electromembrane extraction combined with dispersive liquid-liquid microextraction for determination of thymol from Carum copticum. AB - BACKGROUND: A novel technique using maghemite nanoparticle-decorated hollow fibers to assist electromembrane extraction is proposed. Electromembrane extraction combined with dispersive liquid-liquid microextraction (EME-DLLME) was applied for the extraction of thymol from Carum copticum, followed by gas chromatography with flame ionization detection (GC-FID). RESULTS: The use of maghemite nanoparticle-decorated hollow fibers was found to improve the extraction efficiency of thymol significantly. Important operational parameters, including pH of acceptor phase, extraction time, voltage and temperature, were investigated and optimized. At the optimal conditions, linearity in the range 4 1800 ug L-1 with a determination coefficient of 0.9996 was obtained. The limit of detection was 0.11 ug L-1 (S/N = 3) and the pre-concentration factor was 200. The intra- and inter-day precision was 5.9 and 2.2% respectively. The intra- and inter-day accuracy was higher than 93.6%. CONCLUSION: The results indicated that EME-DLLME/GC-FID is a useful technique for the extraction and determination of thymol in C copticum. (c) 2016 Society of Chemical Industry. PMID- 27404218 TI - Lipid Emulsion in Local Anesthetic Toxicity: Long-winded, Rude, and Right. PMID- 27404219 TI - Adenosine Receptor Adora2b Plays a Mechanistic Role in the Protective Effect of the Volatile Anesthetic Sevoflurane during Liver Ischemia/Reperfusion. AB - BACKGROUND: Liver ischemia/reperfusion (IR) injury is characterized by hepatic tissue damage and an inflammatory response. This is accompanied by the formation and vascular sequestration of platelet-neutrophil conjugates (PNCs). Signaling through Adora2b adenosine receptors can provide liver protection. Volatile anesthetics may interact with adenosine receptors. This study investigates potential antiinflammatory effects of the volatile anesthetic sevoflurane during liver IR. METHODS: Experiments were performed ex vivo with human blood and in a liver IR model with wild-type, Adora2a, and Adora2b mice. The effect of sevoflurane on platelet activation, PNC formation and sequestration, cytokine release, and liver damage (alanine aminotransferase release) was analyzed using flow cytometry, luminometry, and immunofluorescence. Adenosine receptor expression in liver tissue was analyzed using immunohistochemistry and real-time polymerase chain reaction. RESULTS: Ex vivo experiments indicate that sevoflurane inhibits platelet and leukocyte activation (n = 5). During liver IR, sevoflurane (2 Vol%) decreased PNC formation 2.4-fold in wild-type (P < 0.05) but not in Adora2b mice (n >= 5). Sevoflurane reduced PNC sequestration 1.9-fold (P < 0.05) and alanine aminotransferase release 3.5-fold (P < 0.05) in wild-type but not in Adora2b mice (n = 5). In Adora2a mice, sevoflurane also inhibited PNC formation and cytokine release. Sevoflurane diminished cytokine release (n >= 3) and increased Adora2b transcription and expression in liver tissue of wild-types (n = 4). CONCLUSIONS: Our experiments highlight antiinflammatory and tissue-protective properties of sevoflurane during liver IR and reveal a mechanistic role of Adora2b in sevoflurane-associated effects. The targeted use of sevoflurane not only as an anesthetic but also to prevent IR damage is a promising approach in the treatment of critically ill patients. PMID- 27404220 TI - Oxygen Therapy: When Is Too Much Too Much? PMID- 27404221 TI - Effects of Depth of Propofol and Sevoflurane Anesthesia on Upper Airway Collapsibility, Respiratory Genioglossus Activation, and Breathing in Healthy Volunteers. AB - BACKGROUND: Volatile anesthetics and propofol impair upper airway stability and possibly respiratory upper airway dilator muscle activity. The magnitudes of these effects have not been compared at equivalent anesthetic doses. We hypothesized that upper airway closing pressure is less negative and genioglossus activity is lower during deep compared with shallow anesthesia. METHODS: In a randomized controlled crossover study of 12 volunteers, anesthesia with propofol or sevoflurane was titrated using a pain stimulus to identify the threshold for suppression of motor response to electrical stimulation. Measurements included bispectral index, genioglossus electromyography, ventilation, hypopharyngeal pressure, upper airway closing pressure, and change in end-expiratory lung volume during mask pressure drops. RESULTS: A total of 393 attempted breaths during occlusion maneuvers were analyzed. Upper airway closing pressure was significantly less negative at deep versus shallow anesthesia (-10.8 +/- 4.5 vs. 11.3 +/- 4.4 cm H2O, respectively [mean +/- SD]) and correlated with the bispectral index (P < 0.001), indicating a more collapsible airway at deep anesthesia. Respiratory genioglossus activity during airway occlusion was significantly lower at deep compared with light anesthesia (26 +/- 21 vs. 35 +/- 24% of maximal genioglossus activation, respectively; P < 0.001) and correlated with bispectral index (P < 0.001). Upper airway closing pressure and genioglossus activity during airway occlusion did not differ between sevoflurane and propofol anesthesia. CONCLUSIONS: Propofol and sevoflurane anesthesia increased upper airway collapsibility in a dose-dependent fashion with no difference at equivalent anesthetic concentrations. These effects can in part be explained by a dose-dependent inhibiting effect of anesthetics on respiratory genioglossus activity. PMID- 27404222 TI - A Multicenter, Randomized, Controlled Phase IIb Trial of Avoidance of Hyperoxemia during Cardiopulmonary Bypass. AB - BACKGROUND: Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery-associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels. This study aimed to determine whether the avoidance of arterial hyperoxemia decreased oxidative stress and reduced the severity of the multiorgan dysfunction in patients undergoing cardiac surgery utilizing CPB. METHODS: The study was a multicenter, open-label, parallel-group, randomized controlled study of the avoidance of arterial hyperoxemia versus usual care in patients undergoing cardiac surgery involving CPB. Primary outcome was the incidence and severity of AKI. Secondary outcomes included serum biomarkers for CSA-MOD, duration of mechanical ventilation, and length of intensive care and hospital stay. RESULTS: A total of 298 patients were randomized and analyzed at two hospitals in New Zealand and Australia. Mean PaO2 was significantly different between groups during CPB. There was no difference in the development of AKI (intervention arm 72.0% vs. usual care 66.2%; difference, -5.8% [95% CI, -16.1 to 4.7%]; P = 0.28), other markers of organ damage, or intensive care unit and hospital length of stay. CONCLUSIONS: Avoiding modest hyperoxemia during CPB failed to demonstrate any difference in AKI, markers of organ damage, or length of stay. PMID- 27404223 TI - Effect of Intralipid(r) on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. AB - BACKGROUND: Rapid intravenous administration of lipid emulsion has become the standard treatment of severe local anesthetic systemic toxicity. This experiment in volunteers aimed at determining the effect of Intralipid(r) administration on the time to neurologic symptoms. METHODS: Ropivacaine or levobupivacaine was infused intravenously in 16 volunteers (8 mg/min up to 120 mg) with 120 ml Intralipid(r) 20% (Fresenius, Paris France) or placebo infused at T + 2 min). Each subject received all four treatments in a crossover manner. The infusion was stopped after the intended dose had been administered or on occurrence of incipient neurologic signs of toxicity. The primary outcome was time-to-event. In addition, blood ropivacaine and levobupivacaine concentrations were measured. RESULTS: The dose infused was not different whether volunteers received placebo (81.7 +/- 22.3 vs. 80.8 +/- 31.7 mg, ropivacaine vs. levobupivacaine) or Intralipid(r) (75.7 +/- 29.1 vs. 69.4 +/- 26.2 mg, ropivacaine vs. levobupivacaine), P = 0.755, Intralipid(r) versus placebo groups. Plasma concentrations were best modeled with an additional volume of distribution associated with Intralipid(r). Simulations suggested that decreased peak concentrations would be seen if Intralipid(r) was given during a period of increasing concentrations after extravascular administration. CONCLUSIONS: At modestly toxic doses of ropivacaine or levobupivacaine, we were unable to find any effect of the infusion of Intralipid(r) on the time to early signs of neurologic toxicity in volunteers. Peak concentration was decreased by 26 to 30% in the subjects receiving Intralipid(r). Simulations showed that Intralipid(r) might prevent the rapid increase of local anesthetic concentration after extravascular administration. PMID- 27404224 TI - Radiologist variability in assessing the position of the cavoatrial junction on chest radiographs. AB - OBJECTIVE: To assess the variability in identifying the cavoatrial junction (CAJ) on chest X-rays (CXRs) amongst radiologists. METHODS: 23 radiologists (13 consultants and 10 trainees) assessed 25 posteroanterior erect CXRs (including 8 duplicates) and marked the positions of the CAJ. Differences in the CAJ position both within and between observers were evaluated and reported as limits of agreement (LOA), repeatability coefficients (RCs) and intraclass correlation coefficients and were displayed graphically with Bland-Altman plots. RESULTS: The mean difference for within-observer assessments was -0.2 cm (95% LOA, -1.5 to +1.1 cm) and between observers, it was -0.3 cm (95% LOA, -2.5 to +1.8 cm). Intraobserver RCs were marginally lower for consultants than for trainees (1.1 vs 1.5). RCs between observers were comparable (2.1 vs 2.2) for consultants and trainees, respectively. CONCLUSION: This study detected a large interobserver variability of the CAJ position (up to 4.3 cm). This is a significant finding considering that the length of the superior vena cava is reported to be approximately 7 cm. We conclude that there is poor consensus regarding the CAJ position amongst radiologists. ADVANCES IN KNOWLEDGE: No comparisons exist between radiologists in determining CAJ position from CXRs. This report provides evidence of the large observer variability amongst radiologists and adds to the discussion regarding the use of CXRs in validating catheter tip location systems. PMID- 27404225 TI - Enzyme-Triggered Folding of Hydrogels: Toward a Mimic of the Venus Flytrap. AB - External triggers such as pH or temperature can induce hydrogels to swell or shrink rapidly. Recently, these triggers have also been used to alter the three dimensional (3-D) shapes of gels: for example, a flat gel sheet can be induced to fold into a tube. Self-folding gels are reminiscent of natural structures such as the Venus flytrap, which folds its leaves to entrap its prey. They are also of interest for applications in sensing or microrobotics. However, to advance the utility of self-folding gels, the range of triggers needs to be expanded beyond the conventional ones. Toward this end, we have designed a class of gels that change shape in response to very low concentrations of specific biomolecules. The gels are hybrids of three different constituents: (A) polyethylene glycol diacrylate (PEGDA); (B) gelatin methacrylate-co-polyethylene glycol dimethacrylate (GelMA-co-PEGDMA); and (C) N-isopropylacrylamide (NIPA). The thin film hybrid is constructed as a bilayer or sandwich of two layers, with an A/B layer (alternating strips of A and B) sandwiched above a layer of gel C. Initially, when this hybrid gel is placed in water, the C layer is much more swollen than the A/B layer. Despite the swelling mismatch, the sheet remains flat because the A/B layer is very stiff. When collagenase enzyme is added to the water, it cleaves the gelatin chains in B, thus reducing the stiffness of the A/B layer. As a result, the swollen C layer is able to fold over the A/B layer, causing the sheet to transform into a specific shape. The typical transition is from flat sheet to closed hollow tube, and the time scale for this transition decreases with increasing enzyme concentration. Shape transitions are induced by enzyme levels as low as 0.75 U/mL. Interestingly, a shape transition is also induced by adding the lysate of murine fibroblast cells, which contains enzymes from the matrix metalloproteinase (MMP) family at levels around 0.1 U/mL (MMPs are similar to collagenase in their ability to cleave gelatin). We further show that transitions from flat sheets to other shapes such as helices and pancakes can be engineered by altering the design pattern of the gel. Additionally, we have made a rudimentary analog of the Venus flytrap, with two flat gels ("leaves") flanking a central folding gel ("hinge"). When enzyme is added, the hinge bends and brings the leaves together, trapping objects in the middle. PMID- 27404226 TI - The In-Plane Anisotropy of WTe2 Investigated by Angle-Dependent and Polarized Raman Spectroscopy. AB - Tungsten ditelluride (WTe2) is a semi-metallic layered transition metal dichalcogenide with a stable distorted 1T phase. The reduced symmetry of this system leads to in-plane anisotropy in various materials properties. We have systemically studied the in-plane anisotropy of Raman modes in few-layer and bulk WTe2 by angle-dependent and polarized Raman spectroscopy (ADPRS). Ten Raman modes are clearly resolved. Their intensities show periodic variation with sample rotating. We identify the symmetries of the detected modes by quantitatively analyzing the ADPRS results based on the symmetry selection rules. Material absorption effect on the phonon modes with high vibration frequencies is investigated by considering complex Raman tensor elements. We also provide a rapid and nondestructive method to identify the crystallographic orientation of WTe2. The crystallographic orientation is further confirmed by the quantitative atomic-resolution force image. Finally, we find that the atomic vibrational tendency and complexity of detected modes are also reflected in the shrinkage degree defined based on ADPRS, which is confirmed by corresponding density functional calculation. Our work provides a deep understanding of the interaction between WTe2 and light, which will benefit in future studies about the anisotropic physical properties of WTe2 and other in-plane anisotropic materials. PMID- 27404227 TI - The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome. AB - Copy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate beta-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter beta-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21 related disorders including Down Syndrome. PMID- 27404228 TI - Clinical Significance of Proliferative Inflammatory Atrophy in Negative Prostatic Biopsies. AB - PURPOSE: To analyze the association between prostatic proliferative inflammatory atrophy finding in negative prostate biopsies and future detection of prostate cancer (PCa) and its aggressiveness in men subjected to repeat biopsies, due to persistent suspicion of PCa. MATERIALS AND METHODS: Prospective and observational study of 474 men scheduled to repeated PBs. Assessment of PIA and its extension in the previous biopsy. PCa detection rate and tumor aggressiveness. Age, serum total PSA, free PSA, percent free PSA (%fPSA), digital rectal exam (DRE), prostate volume (PV), PSA density (PSAD), PSA kinetics (PSAV and PSADT) findings of PIA and HGPIN, and number of affected cores in previous PBs were included in the univariate and multivariate analysis. Aggressive tumors were considered when any Gleason pattern 4 was found. RESULTS: PCa was detected in 133 men (28.1%). Age, serum total PSA, %fPSA, PV, PSAD, PSAV, PSADT, and PIA finding were significantly associated to PCa detection. However, only age, OR: 1.06 (95%CI: 1.03-1.10), P < 0.01; DRE, OR: 1.76 (95%CI: 1.05-2.92), P = 0.03; %fPSA, OR: 0.96 (95%CI: 0.93-0.99), P = 0.03; PV, OR: 0.98 (95%CI: 0.97-0.99) and PIA finding, OR: 0.49 (95%CI: 0.29-0.83), P < 0.01, were independent predictors of PCa detection. PCa was found in 18% of 159 men with previous PIA finding while in 33% of 315 men without previous PIA (P < 0.01). None of the studied parameters including PIA in the previous biopsy were related with subsequent PCa aggressiveness. CONCLUSIONS: PIA finding in negative biopsies correlates with a decreased frequency of detecting PCa in men with persistent suspicion of PCa. The aggressiveness of future detected tumors was not associated with previous PIA finding. Prostate 76:1501-1506, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27404229 TI - Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells. AB - PHARMOCOLOGICAL RELEVANCE: 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), is a phloroglucinol compound found naturally in Melicope ptelefolia. Melicope ptelefolia has been used traditionally for centuries as natural remedy for wound infections and inflammatory diseases. AIM OF THE STUDY: Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro-inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS stimulated HUVECs was evaluated. RESULTS: It was found that pretreatment with tHGA inhibited monocyte adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E2 (PGE2). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs. CONCLUSION: As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases. PMID- 27404230 TI - Tongqiaohuoxue decoction ameliorates obesity-induced inflammation and the prothrombotic state by regulating adiponectin and plasminogen activator inhibitor 1. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tongqiaohuoxue decoction (THD), a water extract of a mixture of eight species of medicinal herbs, has been used for the treatment of blood stasis and hypercoagulation in traditional East Asian medicine since 18th century. AIM OF THE STUDY: To investigate the in vivo efficacy of THD using high-fat diet (HFD)-induced obese mice with chronic inflammation and a prothrombotic state as an early vascular model. MATERIALS AND METHODS: THD was prepared by hot water extraction and freeze-drying. Male C57BL/6 mice were divided into three groups. Group 1 (NC) mice were fed normal chow. Mice in group 2 (HFD) and 3 (HFD+THD) were fed with HFD for 12 weeks. In addition, Group 3 mice were administered with 100mg/kg body weight THD for 4 weeks after onset of obesity by HFD for 8 weeks. Glucose tolerance tests and histological tissue examinations were performed. The levels of adipokines, inflammatory markers, and prothrombotic markers were assessed. RESULTS: The oral administration of THD for 4 weeks had no effect on the liver, adipose tissue, or total body weight when the HFD and HFD+THD groups were compared. Nevertheless, mice treated in THD interestingly showed a significant increase in adiponectin in blood and adipose tissue. To verify the effect of THD on adiponectin, 3T3-L1 adipocytes were treated with THD; it stimulated adiponectin production in a dose-dependent manner. In the HFD+THD group, pro-inflammatory cytokines were significantly down regulated in the blood, adipose tissue, and liver. Insulin resistance was also notably improved by THD. Simultaneously, THD significantly reduced plasminogen activator inhibitor-1 (PAI-1) levels in serum, adipose tissue, and liver. Fibrin deposition and tPA activity, downstream targets of PAI-1, were also notably reduced in the HFD+THD group compared to the HFD group. CONCLUSIONS: THD improved obesity-induced inflammation and insulin resistance by increasing adiponectin production. Additionally, THD administration exerted an anti-thrombotic effect through the regulation of PAI-1 and fibrinolysis. This study demonstrates the efficacy of a traditional East Asian medicine by providing scientific evidence and suggesting a possible mechanism of action. PMID- 27404231 TI - The Ayurvedic Pharmacopoeia of India, development and perspectives. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The Ayurvedic Pharmacopoeia of India (API) is a unique book of standards describing the quality, purity and strength of selected drugs that are manufactured, distributed, and sold by the licensed manufacturers in pan India. It is developed in two parts; the part one comprises of mono monographs of medicinal substances of natural origin and part two includes selected compound formulations sourced from the schedule - I books under the Drugs and Cosmetics Act, 1940 comprising of popular Ayurvedic classics of different period of times. The first part of the Ayurvedic Formulary of India was published in 1978 and thereafter, the Ayurvedic Pharmacopoeia of India (mono monograph) Part-I, Vol. I was published in the year 1989 and subsequently, the other volumes were published with their legalized status under Drugs and Cosmetics Act, 1940. AIM OF THE STUDY: The study was aimed to bring out the existing knowledge on the Ayurvedic pharmacopoeia with its chronological development reviewed from the ancient Vedic Compendia with its continuum in Ayurvedic classics of different period of time till recent past. MATERIALS AND METHODS: A literary search based on the ancient origin of Ayurveda was carried out. The drug making from the natural resources and utility of the knowledge exist in classical Ayurvedic works of different period of time till composition of the Ayurvedic Pharmacopoeia of India and its importance as official documents of Govt. of India for Standards of Ayurvedic Drugs and its perspectives have been discussed. RESULTS: The present paper reviews on the systemic development and different aspects of drug-making (Pharmacopoeia) with evidence lying in the 5000 years old work of India. During the systematic review of the various works of different period of times (ancient, medieval and modern), it was found that the Ayurvedic Pharmacopoeia of India has its development during 20th Century as an official document of Govt. of India comprising of single drugs monograph and compound formulations. CONCLUSION: In India, the development of the Indian Pharmacopoeia started in 20th Century on the recommendation of the Col. R.N. Chopra Committee and in 1978 the first part of the Ayurvedic formulary of India was published. Subsequently, the amendment in the drugs and cosmetics Act 1940 was brought in 1964 for regulation of the drugs in Indian Systems of Medicine (Ayurveda, Unani and Siddha). Later on the Ayurvedic Pharmacopoeia of India (Mono Monograph) Part-I, Volume I, was published in the year 1989 and the other volumes were published subsequently in different years. PMID- 27404232 TI - Voluntary wheel exercise alters the levels of miR-494 and miR-696 in the skeletal muscle of C57BL/6 mice. AB - The discovery of miRNAs has brought the focus of physiologists to post transcriptional regulation of the skeletal muscle. However, the field of how miRNAs are involved in regulating mitochondrial biogenesis and apoptosis of the skeletal muscle following endurance training is still in its infancy. Twelve male C57BL/6 mice were randomly assigned to either control group (Group C) or voluntary wheel running group (Group E). The Group C was housed in cages mounted with fixed wheels, while mice of Group E were allowed to run on wheels freely for 8weeks. It was found that miR-494 and miR-696 were significantly decreased in the gastrocnemius muscle after 8week voluntary wheel exercise, accompanied with an increase in the mRNA expression of NRF1, BIM and Bcl-XL, an increase in the protein content of PGC-1alpha, and a decrease in the protein content BIM. The lack of correlation between miR-494 and TFAM and BIM, as well as between miR-696 and PGC-1alpha suggests that even though miR-494 and miR-696 are sensitive miRNAs in response to exercise training, other factors or miRNAs might also be important during the regulation of mitochondrial biogenesis and apoptosis. PMID- 27404233 TI - Colour polymorphism. AB - White and Kemp introduce colour polymorphism in animals. PMID- 27404234 TI - What makes medical students better listeners? AB - Diagnosing heart conditions by auscultation is an important clinical skill commonly learnt by medical students. Clinical proficiency for this skill is in decline [1], and new teaching methods are needed. Successful discrimination of heartbeat sounds is believed to benefit mainly from acoustical training [2]. From recent studies of auditory training [3,4] we hypothesized that semantic representations outside the auditory cortex contribute to diagnostic accuracy in cardiac auscultation. To test this hypothesis, we analysed auditory evoked potentials (AEPs) which were recorded from medical students while they diagnosed quadruplets of heartbeat cycles. The comparison of trials with correct (Hits) versus incorrect diagnosis (Misses) revealed a significant difference in brain activity at 280-310 ms after the onset of the second cycle within the left middle frontal gyrus (MFG) and the right prefrontal cortex. This timing and locus suggest that semantic rather than acoustic representations contribute critically to auscultation skills. Thus, teaching auscultation should emphasize the link between the heartbeat sound and its meaning. Beyond cardiac auscultation, this issue is of interest for all fields where subtle but complex perceptual differences identify items in a well-known semantic context. PMID- 27404235 TI - Pre-Columbian monkey tools. AB - Stone tools reveal worldwide innovations in human behaviour over the past three million years [1]. However, the only archaeological report of pre-modern non human animal tool use comes from three Western chimpanzee (Pan troglodytes verus) sites in Cote d'Ivoire, aged between 4.3 and 1.3 thousand years ago (kya) [2]. This anthropocentrism limits our comparative insight into the emergence and development of technology, weakening our evolutionary models [3]. Here, we apply archaeological techniques to a distinctive stone tool assemblage created by a non human animal in the New World, the Brazilian bearded capuchin monkey (Sapajus libidinosus). Wild capuchins at Serra da Capivara National Park (SCNP) use stones to pound open defended food, including locally indigenous cashew nuts [4], and we demonstrate that this activity dates back at least 600 to 700 years. Capuchin stone hammers and anvils are therefore the oldest non-human tools known outside of Africa, opening up to scientific scrutiny questions on the origins and spread of tool use in New World monkeys, and the mechanisms - social, ecological and cognitive - that support primate technological evolution. PMID- 27404236 TI - Meiosis: Cohesins Are Not Just for Sisters Any More. AB - Multiple meiosis-specific cohesion proteins act to facilitate homolog segregation at the first meiotic division. A recent paper demonstrates that meiotic cohesins can be separated into two complexes, one that establishes and maintains intersister cohesion and one that promotes interhomolog adhesion by regulating synaptonemal complex assembly. PMID- 27404237 TI - Future Thinking: Children But Not Apes Consider Multiple Possibilities. AB - When anticipating the future, we draw on our past experience but must take uncertainty into account; for example, while preparing for a trip, we might pack a raincoat and sunglasses because of unpredictable weather. New research shows that the ability to plan for multiple future possibilities may be present in human children from as early as 3-4 years of age, but appears to be lacking in non-human apes. PMID- 27404238 TI - Plant Evolution: What Does It Take To Be an Egg? AB - The genetic regulation of cell patterning within plant gametophytes remains poorly understood. Now, two new studies in the liverwort Marchantia polymorpha shed light on the conserved function of an RKD transcription factor as a key regulator of egg cell fate in the land plant lineage. PMID- 27404239 TI - Ageing: How Do Long-Lived Plants Escape Mutational Meltdown? AB - Some plants can live for thousands of years, facing the problem of preventing accumulation of deleterious mutations. A recent study shows that massive tree stature requires surprisingly few stem cell divisions, and that the mutational load is not proportional to stature, but to branching order. PMID- 27404240 TI - Aging: Lessons for Elderly People from Monkeys. AB - As life expectancy increases, health in the elderly is a growing issue. Health is linked to remaining socially active, but the elderly typically narrow their social networks. The social life of aging monkeys shows interesting parallels, indicating social patterns may be rooted in evolution. PMID- 27404241 TI - Face Recognition: Canonical Mechanisms at Multiple Timescales. AB - Adaptation is ubiquitous in the nervous system, and many possible computational roles have been discussed. A new functional imaging study suggests that, in face recognition, the learning of 'norm faces' and adaptation resulting in perceptual after-effects depend on the same mechanism. PMID- 27404242 TI - Zoology: Invertebrates that Parasitize Invertebrates. AB - The genome of an orthonectid, a group of highly modified parasitic invertebrates, is drastically reduced and compact, yet it shows the bilaterian gene toolkit. Phylogenetic analyses place the enigmatic orthonectids within Spiralia, although their exact placement remains uncertain. PMID- 27404244 TI - Death and the octopus. PMID- 27404243 TI - Protein Modification: Bacterial Effectors Rewrite the Rules of Ubiquitylation. AB - A family of virulence factors from the bacterial pathogen Legionella pneumophila has been discovered to modify human Rab GTPases with ubiquitin. Surprisingly, this modification occurs via a non-canonical mechanism that uses nicotinamide adenine dinucleotide as a cofactor. PMID- 27404245 TI - Comparative thanatology. AB - A quick guide on comparative thanatology, the study of death and dying, particular how individuals respond to a conspecific's death, across animal phylogeny. PMID- 27404246 TI - Carrion flowers. AB - In this Quick Guide, Johnson introduces the reader to carrion flowers, which evolved to mimic rotting flesh. This adaptation attracts insects that facilitate pollination. PMID- 27404247 TI - Efferocytosis. AB - Kumar and Birge introduce efferocytosis - the process by which dead or dying cells are engulfed and digested by phagocytes. PMID- 27404248 TI - Vultures. AB - Buechley and Sekercioglu introduce vultures, the supreme avian scavengers that now face multiple threats. PMID- 27404249 TI - Microbiology of death. AB - Metcalf et al., take a fresh look at the universal question "What happens when we die?" PMID- 27404250 TI - Climate, decay, and the death of the coal forests. AB - After death, most of the biological carbon in organisms (Corg) is returned to the atmosphere as CO2 through the respiration of decomposers and detritivores or by combustion. However, the balance between these processes is not perfect, and when productivity exceeds decomposition, carbon sequestration results. An unparalleled interval of carbon sequestration in Earth's history occurred during the Late Carboniferous (Pennsylvanian) and Permian Periods (ca. 323-252 Ma), when arborescent vascular plants related to living club mosses (Lycophytes), ferns (Monilophytes), horsetails (Equisetophytes) and seed plants (Spermatophytes) formed extensive forests in coastal wetlands. On their death, these plants became buried in sediments, where they transformed into peat, lignite, and, finally, coal. PMID- 27404251 TI - Pyroptosis. AB - Injury and physical trauma may inflict accidental cell death, but we have come to realize during the past four decades that cells may also actively engage cell death when needed. These regulated cell death forms are intrinsically connected with human embryonic development, homeostatic maintenance and disease pathology. For instance, the human body is composed of approximately 10(14) cells, millions of which are removed daily by apoptosis and replaced with newly differentiated cells in order to secure organ functionality. Apoptotic cells are orderly packed in 'apoptotic bodies' for uptake by neighboring cells and professional phagocytes, thereby avoiding deleterious inflammatory responses by circulating leukocytes. Unlike apoptosis, however, more recently identified forms of regulated cell death - such as necroptosis and pyroptosis - are characterized by an early breach of the plasma membrane integrity, which results in extracellular spilling of the intracellular contents. Here, we will describe and discuss this and other features of pyroptosis. PMID- 27404252 TI - Brain death and disorders of consciousness. AB - While often confused by non-medical specialists, brain death and disorders of consciousness such as coma, vegetative state, and minimally conscious state are clearly distinct and unambiguously distinguishable. Moreover, biological models underpin each category uniquely and with increasing precision. In this Primer, we frame the distinctions across the different conditions, point to recent work that advances measurements able to identify their differences, and explain two inter related paradoxes. The first paradox is the brain dead patient whose 'phenotype' betrays the ultimate futility and lack of sustainability of the state. The second paradox is that of patients who retain apparent higher levels of cognitive function but who may be misidentified as remaining in a vegetative state or one of the similar conditions formulated in the recently defined syndrome of cognitive motor dissociation. Building on emerging data and models underlying each of these brain states, we place recent controversies over the assessment of brain dead patients into a scientific and wider societal context. We conclude by placing brain death into a broader conceptual framework that takes account of emerging scientific knowledge about disorders of consciousness. PMID- 27404253 TI - The Expensive Germline and the Evolution of Ageing. AB - The trade-off between survival and reproduction is the bedrock of the evolutionary theory of ageing. The reproductive system regulates ageing of the soma, and removal of germ cells extends somatic lifespan and increases resistance to a broad variety of abiotic and biotic stresses. The general explanation for this somatic response is that reduced reproduction frees up resources for survival. Remarkably, however, the disruption of molecular signaling pathways that regulate ageing increases lifespan without the obligatory reduction in fecundity, thus challenging the key role of the survival-reproduction trade-off. Here, we review the diverse literature on the costs of lifespan extension and suggest that the current paradigm is overly centered on the trade-off between lifespan and fecundity, often neglecting key aspects of fitness, such as development time, defense against parasites and, in particular, the high costs of germline maintenance. Compromised germline maintenance increases germline mutation rate, which reduces offspring fitness and ultimately can terminate germline proliferation across generations. We propose that future work should incorporate the costs of germline maintenance in the study of ageing evolution, as well as in applied biomedical research, by assessing offspring fitness. PMID- 27404254 TI - Programmed Cell Death and Complexity in Microbial Systems. AB - Programmed cell death (PCD) is central to organism development and for a long time was considered a hallmark of multicellularity. Its discovery, therefore, in unicellular organisms presents compelling questions. Why did PCD evolve? What is its ecological effect on communities? To answer these questions, one is compelled to consider the impacts of PCD beyond the cell, for death obviously lowers the fitness of the cell. Here, we examine the ecological effects of PCD in different microbial scenarios and conclude that PCD can increase biological complexity. In mixed microbial communities, the mode of death affects the microenvironment, impacting the interactions between taxa. Where the population comprises groups of relatives, death has a more explicit effect. Death by lysis or other means can be harmful, while PCD can evolve by providing advantages to relatives. The synchronization of death between individuals suggests a group level property is being maintained and the mode of death also appears to have had an impact during the origin of multicellularity. PCD can result in the export of fitness from the cell to the group level via re-usable resources and PCD may also provide a mechanism for how groups beget new groups comprising kin. Furthermore, PCD is a means for solving a central problem of group living - the toxic effects of death by making resources in dying cells beneficial to others. What emerges from the data reviewed here is that while PCD carries an obvious cost to the cell, it can be a driver of complexity in microbial communities. PMID- 27404255 TI - Programmed Cell Death in Unicellular Phytoplankton. AB - Unicellular, planktonic, prokaryotic and eukaryotic photoautotrophs (phytoplankton) have an ancient evolutionary history on Earth during which time they have played key roles in the regulation of marine food webs, biogeochemical cycles, and Earth's climate. Since they represent the basis of aquatic ecosystems, the manner in which phytoplankton die critically determines the flow and fate of photosynthetically fixed organic matter (and associated elements), ultimately constraining nutrient flow. Programmed cell death (PCD) and associated pathway genes, which are triggered by a variety of abiotic (nutrient, light, osmotic) and biotic (virus infection, allelopathy) environmental stresses, have an integral grip on cell fate, and have shaped the ecological success and evolutionary trajectory of diverse phytoplankton lineages. A combination of physiological, biochemical, and genetic techniques in model algal systems has demonstrated a conserved molecular and mechanistic framework of stress surveillance, signaling, and death activation pathways, involving collective and coordinated participation of organelles, redox enzymes, metabolites, and caspase like proteases. This mechanistic understanding has provided insight into the integration of sensing and transduction of stress signals into cellular responses, and the mechanistic interfaces between PCD, cell stress and virus infection pathways. It has also provided insight into the evolution of PCD in unicellular photoautotrophs, the impact of PCD on the fate of natural phytoplankton assemblages and its role in aquatic biogeochemical cycles. PMID- 27404256 TI - Pathogen Tactics to Manipulate Plant Cell Death. AB - Cell death is a vital process for multicellular organisms. Programmed cell death (PCD) functions in a variety of processes including growth, development, and immune responses for homeostasis maintenance. In particular, plants and animals utilize PCD to control pathogen invasion and infected cell populations. Despite some similarity, there are a number of key differences between how these organisms initiate and regulate cell death. In contrast to animals, plants are sessile, lack a circulatory system, and have additional cellular structures, including cell walls and chloroplasts. Plant cells have the autonomous ability to induce localized cell death using conserved eukaryotic pathways as well as unique plant-specific pathways. Thus, in order to successfully infect host cells, pathogens must subvert immune responses and avoid detection to prevent PCD and allow infection. Here we discuss the roles of cell death in plant immune responses and the tactics pathogens utilize to avert cell death. PMID- 27404257 TI - Just So Stories about the Evolution of Apoptosis. AB - Apoptosis is a form of active cell death engaged by developmental cues as well as many different cellular stresses in which the dying cell essentially 'packages' itself for removal. The process of apoptotic cell death, as defined at the molecular level, is unique to the Metazoa (animals). Yet active cell death exists in non-animal organisms, and in some cases molecules involved in such death show some sequence similarities to those involved in apoptosis, leading to extensive speculation regarding the evolution of apoptosis. Here, we examine such speculation from the perspective of the functional properties of molecules of the mitochondrial apoptotic cell death pathway. We suggest scenarios for the evolution of one pathway of apoptosis, the mitochondrial pathway, and consider how they might be tested. We conclude with a 'Just So Story' of how the mitochondrial pathway of apoptosis might have evolved during eukaryotic evolution. PMID- 27404259 TI - Biocompatibility assessment of nanomaterials for environmental safety screening. AB - In view of the extensive use of nanoparticles in countless applications, a fast and effective method for assessing their potential adverse effects on the environment and human health is extremely important. At present, in vitro cell based assays are the standard approach for screening chemicals for cytotoxicity because of their relative simplicity, sensitivity, and cost-effectiveness compared with animal studies. Regrettably, such cell-based viability assays encounter limitations when applied to determining the biological toxicity of nanomaterials, which often interact with assay components and produce unreliable outcomes. We have established a cell-impedance-based, label-free, real-time cell monitoring platform suitable for use in a variety of mammalian cell lines that displays results as cell index values. In addition to this real-time screening platform, other traditional cytotoxicity assays were employed to validate cytotoxicity assessments. We suggest that the cell impedance measurement approach is effective and better suited to determining the cytotoxicity of nanomaterials for environmental safety screening. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1170-1182, 2017. PMID- 27404260 TI - A retrospective chart review evaluating the association of psychological disorders and vitamin D deficiency with celiac disease. AB - BACKGROUND: Data show that deficiencies in Vitamin D have been linked to certain psychological disorders and celiac disease. This study was designed to evaluate the association of psychological comorbidities and vitamin D deficiency with celiac disease. Additionally, any association of psychological comorbidities with gender and age at diagnosis with celiac disease was evaluated. METHODS: This was a retrospective chart review of a cohort of patients with celiac disease presenting for clinical care at a tertiary care referral hospital. Patient age, age at diagnosis of celiac disease, gender, and 25-OH vitamin D levels were recorded. Self-reported history of any psychological and/or psychiatric disease were also recorded and analyzed. RESULTS: Fifty-one patients with celiac disease were included. Forty-seven percent reported a history of a psychological and/or psychiatric disease of which anxiety, depression, and mixed anxiety-depressive disorder were the most common. Age at diagnosis of celiac disease was significantly lower, by ~10 years, in patients with a coexistent psychological comorbidity (P=0.008). Approximately 41% of patients reported vitamin D deficiency, but their mean age was not significantly different from patients without a deficiency. CONCLUSIONS: Celiac disease appears to be diagnosed earlier in patients with associated psychological comorbidity. There was no increased association of vitamin D deficiency and psychological/psychiatric comorbidity in patients with celiac disease. Further research is needed to help us better understand this complex relationship. PMID- 27404261 TI - Supplementary management of functional, temporary alcoholic hepatic damage with Robuvit(r) (French oak wood extract). AB - BACKGROUND: The aim of this registry study was to evaluate Robuvit(r) (French oak wood extract) supplementation in the evolution of moderate functional hepatic failure (MTHF) due to alcohol. Recent studies have indicated the protective effect of oak wood (QR) extracts on liver injury. This registry included patients with MTHF characterized by: decreased albumin levels; increased total bilirubin, altered hepatic functions enzymes, increased oxidative stress, negative viral hepatitis markers. METHODS: The two groups resulted divided into a best management (BM) group and a comparative group (BM + Robuvit(r)): 23 Robuvit(r) patients and 21 comparable controls completed the 12-week registry. At inclusion, blood parameters in the two groups were comparable. RESULTS: During the observation period, the increase in albumin levels was significantly (P<0.05 at 6 weeks) faster and higher in the Robuvit(r) group in comparison with controls. The decrease in ALT-SGPT and AST-ASAT were significantly more important in the supplement group (P<0.05 at 6 and 12 weeks). Alkaline phosphatase was significantly lower at 6 and 12 weeks in Robuvit(r) patients; (Robuvit(r) group's values were significantly better; P<0.05). Total bilirubin improved more in Robuvit(r) subjects at 6 weeks. Results were statistically significant in comparison with controls (P<0.05). Also, direct bilirubin values were higher in the Robuvit(r) group at 6 and 12 weeks (P<0.05). Gamma GT values were normalized at 6 and 12 weeks in the Robuvit(r) group. There was a less important decrease in controls (P<0.05) without normalization at 12 weeks. Plasma free radicals, high at inclusion, showed a more significant decrease in Robuvit(r) subjects (at 6 and 12 weeks), with normalization at 12 weeks. Persisting high values in controls were observed even at 12 weeks (P<0.05). Erythrocytes sedimentation rate (ESR) decreased in both groups with a more important decrease in the Robuvit(r) group (P<0.05). Hepatitis markers were negative when repeated at 6 and 12 weeks. CONCLUSIONS: In conclusion, observations from this pilot, supplement registry study indicate a significant protective activity of the supplementation with Robuvit(r), associated with a very good safety profile, in patients with temporary alcoholic hepatic failure. The activity of Robuvit(r) seems to be mediated by its anti-inflammatory activity associated to its important action on oxidative stress. PMID- 27404262 TI - Endo-SPONGE(r): conservative treatment of an anastomotic leak. PMID- 27404263 TI - Massive prostatomegaly as a proposed unusual etiology of chronic diarrhea predominant IBS with rectal urgency: symptomatic relief after radical prostatectomy. PMID- 27404258 TI - Common and Divergent Mechanisms in Developmental Neuronal Remodeling and Dying Back Neurodegeneration. AB - Cell death is an inherent process that is required for the proper wiring of the nervous system. Studies over the last four decades have shown that, in a parallel developmental pathway, axons and dendrites are eliminated without the death of the neuron. This developmentally regulated 'axonal death' results in neuronal remodeling, which is an essential mechanism to sculpt neuronal networks in both vertebrates and invertebrates. Studies across various organisms have demonstrated that a conserved strategy in the formation of adult neuronal circuitry often involves generating too many connections, most of which are later eliminated with high temporal and spatial resolution. Can neuronal remodeling be regarded as developmentally and spatially regulated neurodegeneration? It has been previously speculated that injury-induced degeneration (Wallerian degeneration) shares some molecular features with 'dying back' neurodegenerative diseases. In this opinion piece, we examine the similarities and differences between the mechanisms regulating neuronal remodeling and those being perturbed in dying back neurodegenerative diseases. We focus primarily on amyotrophic lateral sclerosis and peripheral neuropathies and highlight possible shared pathways and mechanisms. While mechanistic data are only just beginning to emerge, and despite the inherent differences between disease-oriented and developmental processes, we believe that some of the similarities between these developmental and disease initiated degeneration processes warrant closer collaborations and crosstalk between these different fields. PMID- 27404264 TI - Comorbid immunopathological affections in outpatients with inflammatory bowel disease: a prospective study. PMID- 27404265 TI - Familial adenomatous polyposis small bowel surveillance: could indicators for video-capsule endoscopy be ascertained? PMID- 27404266 TI - Pancreatic neuroendocrine tumors: contemporary diagnosis and management. AB - Pancreatic neuroendocrine tumors (PNETs) are neoplasms that arise from the hormone producing cells of the islets of Langerhans, also known as pancreatic islet cells. PNETs are considered a subgroup of neuroendocrine tumors, and have unique biology, natural history and clinical management. These tumors are classified as 'functional' or 'non-functional' depending on whether they release peptide hormones that produce specific hormone- related symptoms, usually in established patterns based on tumor subtype. This manuscript will review pancreatic neuroendocrine tumor subtypes, syndromes, diagnosis, and clinical management. PMID- 27404267 TI - "I've Been a Long Time Leaving": The Role of Limited Skill Transferability in Increasing Suicide-Related Cognitions and Behavior in Veterinarians. AB - Barriers to occupational mobility were investigated to determine whether they increased reported suicide-related cognitions and behavior over 12 months. This was explored in a two-wave longitudinal study. Intention to leave, depression, perceived skill transferability, and suicide-related cognitions and behavior was measured at both time points approximately 12 months apart. Results indicated that when there was a high intention to leave at T1, reported suicide-related cognitions and behavior increased over 12 months only when skill transferability to other professions was perceived to be limited. Findings support the role of limited occupational mobility in suicide-related cognitions and behavior. PMID- 27404268 TI - Population Approaches to Prevention of Type 2 Diabetes. AB - Martin White argues that whole population interventions will be needed in addition to those targeted to people at high risk in order to respond to the global challenge of type 2 diabetes. PMID- 27404269 TI - Timescale- and Sensory Modality-Dependency of the Central Tendency of Time Perception. AB - When individuals are asked to reproduce intervals of stimuli that are intermixedly presented at various times, longer intervals are often underestimated and shorter intervals overestimated. This phenomenon may be attributed to the central tendency of time perception, and suggests that our brain optimally encodes a stimulus interval based on current stimulus input and prior knowledge of the distribution of stimulus intervals. Two distinct systems are thought to be recruited in the perception of sub- and supra-second intervals. Sub-second timing is subject to local sensory processing, whereas supra-second timing depends on more centralized mechanisms. To clarify the factors that influence time perception, the present study investigated how both sensory modality and timescale affect the central tendency. In Experiment 1, participants were asked to reproduce sub- or supra-second intervals, defined by visual or auditory stimuli. In the sub-second range, the magnitude of the central tendency was significantly larger for visual intervals compared to auditory intervals, while visual and auditory intervals exhibited a correlated and comparable central tendency in the supra-second range. In Experiment 2, the ability to discriminate sub-second intervals in the reproduction task was controlled across modalities by using an interval discrimination task. Even when the ability to discriminate intervals was controlled, visual intervals exhibited a larger central tendency than auditory intervals in the sub-second range. In addition, the magnitude of the central tendency for visual and auditory sub-second intervals was significantly correlated. These results suggest that a common modality independent mechanism is responsible for the supra-second central tendency, and that both the modality-dependent and modality-independent components of the timing system contribute to the central tendency in the sub-second range. PMID- 27404270 TI - Colorectal Cancer with BRAF D594G Mutation Is Not Associated with Microsatellite Instability or Poor Prognosis. AB - OBJECTIVE: BRAF D594G mutations in colorectal cancer patients are not clearly understood. We retrospectively investigated the clinicopathological features of colorectal cancers with BRAF D594G mutations. METHODS: We selected 908 colorectal cancer patients who underwent surgical resection from January 2008 to January 2013, and assessed BRAF, KRAS, microsatellite instability, and CpG island methylator phenotype (CIMP). RESULTS: We detected BRAF D594G in 7 patients and BRAF V600E in 45 patients. The clinicopathological features of cancers with BRAF D594G mutation were similar to those with BRAF wild-type, but differed from those with BRAF V600E mutations. Regarding microsatellite instability status, 44.4% of cases with BRAF V600E mutations exhibited high microsatellite instability, compared to 14.3% of those with BRAF D594G mutations and 4.4% of those with BRAF wild-type. There were no CIMP-positive tumors in cancers with BRAF D594G mutations, whereas 67.8% of tumors with BRAF V600E mutations were CIMP-positive. In stage IV cancers, the survival rates of patients at 2 years were 8.5, 50.0, and 68.2% in the BRAF V600E mutation, BRAF D594G mutation, and BRAF wild-type groups, respectively. CONCLUSION: Colorectal cancers with BRAF D594G mutations exhibit similar clinicopathological features, microsatellite instability status, and prognosis as those with BRAF wild-type. PMID- 27404271 TI - High-Resolution Spatial Distribution and Estimation of Access to Improved Sanitation in Kenya. AB - BACKGROUND: Access to sanitation facilities is imperative in reducing the risk of multiple adverse health outcomes. A distinct disparity in sanitation exists among different wealth levels in many low-income countries, which may hinder the progress across each of the Millennium Development Goals. METHODS: The surveyed households in 397 clusters from 2008-2009 Kenya Demographic and Health Surveys were divided into five wealth quintiles based on their national asset scores. A series of spatial analysis methods including excess risk, local spatial autocorrelation, and spatial interpolation were applied to observe disparities in coverage of improved sanitation among different wealth categories. The total number of the population with improved sanitation was estimated by interpolating, time-adjusting, and multiplying the surveyed coverage rates by high-resolution population grids. A comparison was then made with the annual estimates from United Nations Population Division and World Health Organization /United Nations Children's Fund Joint Monitoring Program for Water Supply and Sanitation. RESULTS: The Empirical Bayesian Kriging interpolation produced minimal root mean squared error for all clusters and five quintiles while predicting the raw and spatial coverage rates of improved sanitation. The coverage in southern regions was generally higher than in the north and east, and the coverage in the south decreased from Nairobi in all directions, while Nyanza and North Eastern Province had relatively poor coverage. The general clustering trend of high and low sanitation improvement among surveyed clusters was confirmed after spatial smoothing. CONCLUSIONS: There exists an apparent disparity in sanitation among different wealth categories across Kenya and spatially smoothed coverage rates resulted in a closer estimation of the available statistics than raw coverage rates. Future intervention activities need to be tailored for both different wealth categories and nationally where there are areas of greater needs when resources are limited. PMID- 27404272 TI - Identification and Validation of Loci Governing Seed Coat Color by Combining Association Mapping and Bulk Segregation Analysis in Soybean. AB - Soybean seed coat exists in a range of colors from yellow, green, brown, black, to bicolor. Classical genetic analysis suggested that soybean seed color was a moderately complex trait controlled by multi-loci. However, only a couple of loci could be detected using a single biparental segregating population. In this study, a combination of association mapping and bulk segregation analysis was employed to identify genes/loci governing this trait in soybean. A total of 14 loci, including nine novel and five previously reported ones, were identified using 176,065 coding SNPs selected from entire SNP dataset among 56 soybean accessions. Four of these loci were confirmed and further mapped using a biparental population developed from the cross between ZP95-5383 (yellow seed color) and NY279 (brown seed color), in which different seed coat colors were further dissected into simple trait pairs (green/yellow, green/black, green/brown, yellow/black, yellow/brown, and black/brown) by continuously developing residual heterozygous lines. By genotyping entire F2 population using flanking markers located in fine-mapping regions, the genetic basis of seed coat color was fully dissected and these four loci could explain all variations of seed colors in this population. These findings will be useful for map-based cloning of genes as well as marker-assisted breeding in soybean. This work also provides an alternative strategy for systematically isolating genes controlling relative complex trait by association analysis followed by biparental mapping. PMID- 27404273 TI - Measurement of the Absolute Magnitude and Time Courses of Mitochondrial Membrane Potential in Primary and Clonal Pancreatic Beta-Cells. AB - The aim of this study was to simplify, improve and validate quantitative measurement of the mitochondrial membrane potential (DeltapsiM) in pancreatic beta-cells. This built on our previously introduced calculation of the absolute magnitude of DeltapsiM in intact cells, using time-lapse imaging of the non quench mode fluorescence of tetramethylrhodamine methyl ester and a bis-oxonol plasma membrane potential (DeltapsiP) indicator. DeltapsiM is a central mediator of glucose-stimulated insulin secretion in pancreatic beta-cells. DeltapsiM is at the crossroads of cellular energy production and demand, therefore precise assay of its magnitude is a valuable tool to study how these processes interplay in insulin secretion. Dispersed islet cell cultures allowed cell type-specific, single-cell observations of cell-to-cell heterogeneity of DeltapsiM and DeltapsiP. Glucose addition caused hyperpolarization of DeltapsiM and depolarization of DeltapsiP. The hyperpolarization was a monophasic step increase, even in cells where the DeltapsiP depolarization was biphasic. The biphasic response of DeltapsiP was associated with a larger hyperpolarization of DeltapsiM than the monophasic response. Analysis of the relationships between DeltapsiP and DeltapsiM revealed that primary dispersed beta-cells responded to glucose heterogeneously, driven by variable activation of energy metabolism. Sensitivity analysis of the calibration was consistent with beta-cells having substantial cell-to-cell variations in amounts of mitochondria, and this was predicted not to impair the accuracy of determinations of relative changes in DeltapsiM and DeltapsiP. Finally, we demonstrate a significant problem with using an alternative DeltapsiM probe, rhodamine 123. In glucose-stimulated and oligomycin-inhibited beta-cells the principles of the rhodamine 123 assay were breached, resulting in misleading conclusions. PMID- 27404274 TI - Deciduous trees are a large and overlooked sink for snowmelt water in the boreal forest. AB - The terrestrial water cycle contains large uncertainties that impact our understanding of water budgets and climate dynamics. Water storage is a key uncertainty in the boreal water budget, with tree water storage often ignored. The goal of this study is to quantify tree water content during the snowmelt and growing season periods for Alaskan and western Canadian boreal forests. Deciduous trees reached saturation between snowmelt and leaf-out, taking up 21-25% of the available snowmelt water, while coniferous trees removed <1%. We found that deciduous trees removed 17.8-20.9 billion m(3) of snowmelt water, which is equivalent to 8.7-10.2% of the Yukon River's annual discharge. Deciduous trees transpired 2-12% (0.4-2.2 billion m(3)) of the absorbed snowmelt water immediately after leaf-out, increasing favorable conditions for atmospheric convection, and an additional 10-30% (2.0-5.2 billion m(3)) between leaf-out and mid-summer. By 2100, boreal deciduous tree area is expected to increase by 1-15%, potentially resulting in an additional 0.3-3 billion m(3) of snowmelt water removed from the soil per year. This study is the first to show that deciduous tree water uptake of snowmelt water represents a large but overlooked aspect of the water balance in boreal watersheds. PMID- 27404275 TI - The effect of information on preferences for treatments of metastatic renal cell carcinoma. AB - OBJECTIVE: Limited information exists regarding the effect of uncertainty in outcomes on patient preferences for metastatic renal cell carcinoma (mRCC) treatments. This study tested the effect on patients' preferences and willingness to tolerate toxicities when patients were provided with information about possible correlations between treatment-related toxicities and efficacy. RESEARCH DESIGN AND METHODS: Patients with self-reported RCC diagnosis completed an online survey. Respondents were randomly assigned to the information treatment (i.e. information about the possible correlation). Medicines were defined by progression-free survival (PFS), three toxicities potentially correlated with PFS, and one toxicity uncorrelated with PFS. Direct-elicitation questions measured willingness to tolerate the toxicities, preferences for medicines with higher toxicity but a higher chance of longer PFS, and preferences for medicines with higher toxicity during treatment and a 2 week dosing schedule break. A discrete-choice experiment (DCE) tested the effect of information on relative preferences for medication attributes. RESULTS: A total of 378 RCC patients completed the survey. Respondents who received the information reported greater willingness to accept more severe toxicities and preferred treatment with a higher chance of longer PFS but more severe toxicities. The DCE results were consistent with the hypothesis that the information increased willingness to tolerate toxicities; however, the results were only statistically significant for changes in fatigue (none to severe; p < 0.05) and hypertension (none to manageable; p < 0.05). LIMITATIONS: Online recruitment through patient support groups may limit generalizability to the population of patients with mRCC who would be candidates for the targeted therapies. CONCLUSIONS: The findings suggest that RCC patients have diverse preferences but may be willing to continue targeted therapies, even in the presence of severe toxicities, if there is a chance of improved clinical benefit. Physicians should provide patients with comprehensive information about medication features, including toxicities and efficacy (and their potential correlation), to improve compliance and optimize outcomes. PMID- 27404276 TI - Modelling the sensitivity of life history traits to climate change in a temporary pool crustacean. AB - Temporary pool inhabitants face altered inundation regimes under climate change. While their exposure to these changes has received considerable attention, few studies have investigated their sensitivity or adaptability. Here, we use zooplankton as a model to explore how decreasing hydroperiods affect extinction risks and assess whether changes in life history traits could promote persistence. For this, we construct a three-stage matrix population model parameterised with realistic life-history values for the fairy shrimp Branchipodopsis wolfi from pools with varying hydroperiods. Our results suggest that extinction risks increase drastically once the median hydroperiod drops below a critical threshold. Although changes in life-history parameters could potentially compensate for this risk, the relative importance of each trait for population growth depends on the median hydroperiod. For example, survival of dormant eggs seemed to be most important when hydroperiods were short while the survival of freshly laid eggs and adult individuals were more important in longer lived pools. Overall, this study demonstrates that zooplankton species are sensitive to climate change and that the adaptive capacity of organisms from temporary pools with dissimilar hydrology hinges on selection of different life history traits. PMID- 27404277 TI - Compact Lens-less Digital Holographic Microscope for MEMS Inspection and Characterization. AB - A micro-electro-mechanical-system (MEMS) is a widely used component in many industries, including energy, biotechnology, medical, communications, and automotive. However, effective inspection and characterization metrology systems are needed to ensure the functional reliability of MEMS. This study presents a system based on digital holography as a tool for MEMS metrology. Digital holography has gained increasing attention in the past 20 years. With the fast development and decreasing cost of sensor arrays, resolution of such systems has increased broadening potential applications. Thus, it has attracted attention from both research and industry sides as a potential reliable tool for industrial metrology. Indeed, by recording the interference pattern between an object beam (which contains sample height information) and a reference beam on a CCD camera, one can retrieve the quantitative phase information of an object. However, most of digital holographic systems are bulky and thus not easy to implement on industry production lines. The novelty of the system presented is that it is lens less and thus very compact. In this study, it is shown that the Compact Digital Holographic Microscope (CDHM) can be used to evaluate several characteristics typically consider as criteria in MEMS inspections. The surface profiles of MEMS in both static and dynamic conditions are presented. Comparison with AFM is investigated to validate the accuracy of the CDHM. PMID- 27404278 TI - Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa. AB - Bacterial resistance to traditional antibiotics has driven research attempts to identify new drug targets in recently discovered regulatory pathways. Regulatory systems that utilize intracellular cyclic di-GMP (c-di-GMP) as a second messenger are one such class of target. c-di-GMP is a signaling molecule found in almost all bacteria that acts to regulate an extensive range of processes including antibiotic resistance, biofilm formation and virulence. The understanding of how c-di-GMP signaling controls aspects of antibiotic resistant biofilm development has suggested approaches whereby alteration of the cellular concentrations of the nucleotide or disruption of these signaling pathways may lead to reduced biofilm formation or increased susceptibility of the biofilms to antibiotics. We describe a simple high-throughput bioreporter protocol, based on green fluorescent protein (GFP), whose expression is under the control of the c-di-GMP responsive promoter cdrA, to rapidly screen for small molecules with the potential to modulate c-di GMP cellular levels in Pseudomonas aeruginosa (P. aeruginosa). This simple protocol can screen upwards of 3,500 compounds within 48 hours and has the ability to be adapted to multiple microorganisms. PMID- 27404279 TI - Multi-scale factors influencing the characteristics of avian communities in urban parks across Beijing during the breeding season. AB - Understanding the factors that influence the characteristics of avian communities using urban parks at both the patch and landscape level is important to focus management effort towards enhancing bird diversity. Here, we investigated this issue during the breeding season across urban parks in Beijing, China, using high resolution satellite imagery. Fifty-two bird species were recorded across 29 parks. Analysis of residence type of birds showed that passengers were the most prevalent (37%), indicating that Beijing is a major node in the East Asian Australasian Flyway. Park size was crucial for total species abundance, but foliage height diversity was the most important factor influencing avian species diversity. Thus, optimizing the configuration of vertical vegetation structure in certain park areas is critical for supporting avian communities in urban parks. Human visitation also showed negative impact on species diversity. At the landscape level, the percentage of artificial surface and largest patch index of woodland in the buffer region significantly affected total species richness, with insectivores and granivores being more sensitive to the landscape pattern of the buffer region. In conclusion, urban birds in Beijing are influenced by various multi-scale factors; however, these effects vary with different feeding types. PMID- 27404280 TI - Multiplex amplicon sequencing for microbe identification in community-based culture collections. AB - Microbiome analysis using metagenomic sequencing has revealed a vast microbial diversity associated with plants. Identifying the molecular functions associated with microbiome-plant interaction is a significant challenge concerning the development of microbiome-derived technologies applied to agriculture. An alternative to accelerate the discovery of the microbiome benefits to plants is to construct microbial culture collections concomitant with accessing microbial community structure and abundance. However, traditional methods of isolation, cultivation, and identification of microbes are time-consuming and expensive. Here we describe a method for identification of microbes in culture collections constructed by picking colonies from primary platings that may contain single or multiple microorganisms, which we named community-based culture collections (CBC). A multiplexing 16S rRNA gene amplicon sequencing based on two-step PCR amplifications with tagged primers for plates, rows, and columns allowed the identification of the microbial composition regardless if the well contains single or multiple microorganisms. The multiplexing system enables pooling amplicons into a single tube. The sequencing performed on the PacBio platform led to recovery near-full-length 16S rRNA gene sequences allowing accurate identification of microorganism composition in each plate well. Cross-referencing with plant microbiome structure and abundance allowed the estimation of diversity and abundance representation of microorganism in the CBC. PMID- 27404281 TI - The role of dimensionality in neuronal network dynamics. AB - Recent results from network theory show that complexity affects several dynamical properties of networks that favor synchronization. Here we show that synchronization in 2D and 3D neuronal networks is significantly different. Using dissociated hippocampal neurons we compared properties of cultures grown on a flat 2D substrates with those formed on 3D graphene foam scaffolds. Both 2D and 3D cultures had comparable glia to neuron ratio and the percentage of GABAergic inhibitory neurons. 3D cultures because of their dimension have many connections among distant neurons leading to small-world networks and their characteristic dynamics. After one week, calcium imaging revealed moderately synchronous activity in 2D networks, but the degree of synchrony of 3D networks was higher and had two regimes: a highly synchronized (HS) and a moderately synchronized (MS) regime. The HS regime was never observed in 2D networks. During the MS regime, neuronal assemblies in synchrony changed with time as observed in mammalian brains. After two weeks, the degree of synchrony in 3D networks decreased, as observed in vivo. These results show that dimensionality determines properties of neuronal networks and that several features of brain dynamics are a consequence of its 3D topology. PMID- 27404282 TI - NADH:Cytochrome b5 Reductase and Cytochrome b5 Can Act as Sole Electron Donors to Human Cytochrome P450 1A1-Mediated Oxidation and DNA Adduct Formation by Benzo[a]pyrene. AB - Benzo[a]pyrene (BaP) is a human carcinogen that covalently binds to DNA after activation by cytochrome P450 (P450). Here, we investigated whether NADH:cytochrome b5 reductase (CBR) in the presence of cytochrome b5 can act as sole electron donor to human P450 1A1 during BaP oxidation and replace the canonical NADPH:cytochrome P450 reductase (POR) system. We also studied the efficiencies of the coenzymes of these reductases, NADPH as a coenzyme of POR, and NADH as a coenzyme of CBR, to mediate BaP oxidation. Two systems containing human P450 1A1 were utilized: human recombinant P450 1A1 expressed with POR, CBR, epoxide hydrolase, and cytochrome b5 in Supersomes and human recombinant P450 1A1 reconstituted with POR and/or with CBR and cytochrome b5 in liposomes. BaP-9,10 dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione, BaP-9-ol, BaP-3 ol, a metabolite of unknown structure, and two BaP-DNA adducts were generated by the P450 1A1-Supersomes system, both in the presence of NADPH and in the presence of NADH. The major BaP-DNA adduct detected by (32)P-postlabeling was characterized as 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro BaP (assigned adduct 1), while the minor adduct is probably a guanine adduct derived from 9-hydroxy-BaP-4,5-epoxide (assigned adduct 2). BaP-3-ol as the major metabolite, BaP-9-ol, BaP-1,6-dione, BaP-3,6-dione, an unknown metabolite, and adduct 2 were observed in the system using P450 1A1 reconstituted with POR plus NADPH. When P450 1A1 was reconstituted with CBR and cytochrome b5 plus NADH, BaP 3-ol was the predominant metabolite too, and an adduct 2 was also generated. Our results demonstrate that the NADH/cytochrome b5/CBR system can act as the sole electron donor both for the first and second reduction of P450 1A1 during the oxidation of BaP in vitro. They suggest that NADH-dependent CBR can replace NADPH dependent POR in the P450 1A1-catalyzed metabolism of BaP. PMID- 27404283 TI - Serum proteomic profiles of depressive subtypes. AB - Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, q<0.05) and between atypical depression and controls (23 analytes, q<0.05). Eight of the nine markers differing between the atypical and melancholic subtype overlapped with markers from the comparison between atypical subtype and controls (mesothelin, leptin, IGFBP1, IGFBP2, FABPa, insulin, C3 and B2M), and were mainly involved in cellular communication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression. PMID- 27404284 TI - Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression. AB - Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1(-/-) prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1(-/-) mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1(-/-) mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression. PMID- 27404285 TI - Association between cerebral cannabinoid 1 receptor availability and body mass index in patients with food intake disorders and healthy subjects: a [(18)F]MK 9470 PET study. AB - Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12.5-40.6 kg/m(2)) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5-26.6 kg/m(2)). The association between regional CB1R availability and BMI was assessed within predefined homeostatic and reward-related regions of interest using voxel-based linear regression analyses. CB1R availability was inversely associated with BMI in homeostatic brain regions such as the hypothalamus and brainstem areas in both patients with FID and healthy subjects. However, in FID patients, CB1R availability was also negatively correlated with BMI throughout the mesolimbic reward system (midbrain, striatum, insula, amygdala and orbitofrontal cortex), which constitutes the key circuit implicated in processing appetitive motivation and hedonic value of perceived food rewards. Our results indicate that the cerebral homeostatic CB1R system is inextricably linked to BMI, with additional involvement of reward areas under conditions of disordered body weight. PMID- 27404286 TI - Effects of chronic variable stress on cognition and Bace1 expression among wild type mice. AB - Stressful life events, activation of the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoids are now thought to have a role in the development of several neurodegenerative and psychiatric disorders including Alzheimer's disease (AD) through mechanisms that may include exacerbation of cognitive impairment, neuronal loss, and beta-amyloid (Abeta) and tau neuropathology. In the current study, we use a wild-type mouse model to demonstrate that chronic variable stress impairs cognitive function and that aged mice are particularly susceptible. We also find that stress exposure is associated with a 1.5- to 2-fold increase in the expression of Bace1 in the hippocampus of young adult mice and the hippocampus, prefrontal cortex and amygdala of aged mice. Further, the increased expression of Bace1 was associated with decreased methylation of several CpGs in the Bace1 promoter region. In a second series of experiments, exposure to environmental enrichment (EE) prevented the stress-related changes in cognition, gene expression and DNA methylation. Together, these findings re-affirm the adverse effects of stress on cognition and further suggest that aged individuals are especially susceptible. In addition, demonstrating that chronic stress results in decreased DNA methylation and increased expression of Bace1 in the brain may provide a novel link between stress, Abeta pathology and AD. Finally, understanding the mechanisms by which EE prevented the effects of stress on cognition and Bace1 expression will be an important area of future study that may provide insights into novel approaches to the treatment of AD. PMID- 27404288 TI - The Nature and Variability of Automated Practice Alerts Derived from Electronic Health Records in a U.S. Nationwide Critical Care Research Network. AB - RATIONALE: The nature, variability, and extent of early warning clinical practice alerts derived from automated query of electronic health records (e-alerts) currently used in acute care settings for clinical care or research is unknown. OBJECTIVES: To describe e-alerts in current use in acute care settings at medical centers participating in a nationwide critical care research network. METHODS: We surveyed investigators at 38 institutions involved in the National Institutes of Health-funded Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) for quantitative and qualitative analysis. MEASUREMENTS AND MAIN RESULTS: Thirty sites completed the survey (79% response rate). All sites used electronic health record systems. Epic Systems was used at 56% of sites; the others used alternate commercially available vendors or homegrown systems. Respondents at 57% of sites represented in this survey used e-alerts. All but 1 of these 17 sites used an e-alert for early detection of sepsis-related syndromes, and 35% used an e-alert for pneumonia. E-alerts were triggered by abnormal laboratory values (37%), vital signs (37%), or radiology reports (15%) and were used about equally for clinical decision support and research. Only 59% of sites with e-alerts have evaluated them either for accuracy or for validity. CONCLUSIONS: A majority of the research network sites participating in this survey use e-alerts for early notification of potential threats to hospitalized patients; however, there was significant variability in the nature of e-alerts between institutions. Use of one common electronic health record vendor at more than half of the participating sites suggests that it may be possible to standardize e-alerts across multiple sites in research networks, particularly among sites using the same medical record platform. PMID- 27404289 TI - Efficacy of Intravitreal Bevacizumab for Recurrent Central Serous Chorioretinopathy in Patients Who Had Previously Responded Well to the Same Therapy. AB - PURPOSE: To investigate the efficacy of intravitreal bevacizumab therapy in the treatment of recurrent central serous chorioretinopathy (CSC) that had previously resolved after intravitreal bevacizumab administration. METHODS: This retrospective, observational study included 24 eyes from 24 patients with recurrent CSC who had previously responded to intravitreal bevacizumab. Patients were classified into the responder group when resolution of serous retinal detachment was noted within 3 months after intravitreal bevacizumab (1.25 mg/0.05 mL) administration; the remaining patients were classified into the non-responder group. Patient characteristics were compared between the 2 groups. RESULTS: Ten eyes (42%) were included in the responder group, and 14 eyes (58%) were included in the non-responder group. Patients in the responder group were significantly older (mean age, 47.0 +/- 4.5 years) than those in the non-responder group (mean age, 40.9 +/- 5.5 years; P = 0.023). The visual acuity of the patients in the responder group was significantly worse than that of the patients in the non responder group at the time of the first (mean 0.25 +/- 0.15 vs. 0.13 +/- 0.15) and second episodes (0.24 +/- 0.14 vs. 0.14 +/- 0.18; P = 0.040 and P = 0.021 for the first and second episodes, respectively). CONCLUSIONS: Repeated intravitreal bevacizumab can be considered a useful treatment option for relatively older patients with CSC who previously responded well to the same therapy. The results of the present study also suggest that a vascular endothelial growth factor dependent pathologic process may be involved in CSC in older subjects. PMID- 27404287 TI - Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders. AB - Autism spectrum disorders (ASD) are highly heritable and genetically complex conditions. Although highly penetrant mutations in multiple genes have been identified, they account for the etiology of <1/3 of cases. There is also strong evidence for environmental contribution to ASD, which can be mediated by still poorly explored epigenetic modifications. We searched for methylation changes on blood DNA of 53 male ASD patients and 757 healthy controls using a methylomic array (450K Illumina), correlated the variants with transcriptional alterations in blood RNAseq data, and performed a case-control association study of the relevant findings in a larger cohort (394 cases and 500 controls). We found 700 differentially methylated CpGs, most of them hypomethylated in the ASD group (83.9%), with cis-acting expression changes at 7.6% of locations. Relevant findings included: (1) hypomethylation caused by rare genetic variants (meSNVs) at six loci (ERMN, USP24, METTL21C, PDE10A, STX16 and DBT) significantly associated with ASD (q-value <0.05); and (2) clustered epimutations associated to transcriptional changes in single-ASD patients (n=4). All meSNVs and clustered epimutations were inherited from unaffected parents. Resequencing of the top candidate genes also revealed a significant load of deleterious mutations affecting ERMN in ASD compared with controls. Our data indicate that inherited methylation alterations detectable in blood DNA, due to either genetic or epigenetic defects, can affect gene expression and contribute to ASD susceptibility most likely in an additive manner, and implicate ERMN as a novel ASD gene. PMID- 27404290 TI - Generation and Identification of GM-CSF Derived Alveolar-like Macrophages and Dendritic Cells From Mouse Bone Marrow. AB - Macrophages and dendritic cells (DCs) are innate immune cells found in tissues and lymphoid organs that play a key role in the defense against pathogens. However, they are difficult to isolate in sufficient numbers to study them in detail, therefore, in vitro models have been developed. In vitro cultures of bone marrow-derived macrophages and dendritic cells are well-established and valuable methods for immunological studies. Here, a method for culturing and identifying both DCs and macrophages from a single culture of primary mouse bone marrow cells using the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) is described. This protocol is based on the established procedure first developed by Lutz et al. in 1999 for bone marrow-derived DCs. The culture is heterogeneous, and MHCII and fluoresceinated hyaluronan (FL-HA) are used to distinguish macrophages from immature and mature DCs. These GM-CSF derived macrophages provide a convenient source of in vitro derived macrophages that closely resemble alveolar macrophages in both phenotype and function. PMID- 27404292 TI - Copper-catalyzed divergent oxidative pathways of 2-naphthol derivatives: ortho naphthoquinones versus 2-BINOLs. AB - Catalyst-dependent divergent pathways of 2-naphthol derivatives have been investigated. A readily available CuCl2-DMAP catalyst system promotes the aerobic oxidation of 2-naphthol derivatives to ortho-naphthoquinones whereas switching the catalyst system to Cu(OAc)2-DBN under an argon atmosphere allows the oxidative coupling of 2-naphthols to 1,1'-bi-2-naphthols (BINOLs) in good to excellent yields. PMID- 27404291 TI - A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors. AB - The human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low MUM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays, and its low cytotoxicity in vitro, suggested its potential for drug development. PMID- 27404294 TI - Small-bowel Surveillance in Patients With Peutz-Jeghers Syndrome: Comparing Magnetic Resonance Enteroclysis and Double Balloon Enteroscopy. AB - BACKGROUND AND STUDY AIMS: Small-bowel surveillance with polypectomy of polyps >=15 mm prevents complications in patients with Peutz-Jeghers syndrome (PJS). We aimed to compare magnetic resonance enteroclysis (MRE) and double balloon enteroscopy (DBE) for diagnostic yield of these polyps and for patient preference. MATERIALS AND METHODS: PJS patients prospectively underwent MRE followed by proximal DBE within 20 weeks. Endoscopists were blinded to the MRE results. We compared number of polyps >=15 mm detected by MRE and DBE. Patients' perceptions of both procedures were assessed using questionnaires. RESULTS: Fifteen PJS patients (67% males, median age 47 y) underwent both MRE and DBE. Polyps >=15 mm were identified by MRE and/or DBE in 12/15 (80%) patients. There was no significant difference in the detection of polyps >=15 mm (38 by MRE vs. 50 by DBE, P=0.37). Sensitivity for these polyps was 62% (38/61) for MRE and 82% (50/61) for DBE. Patients' perceived shame and burden did not differ significantly between MRE and DBE. Patients reported significantly more pain during preparation for MRE than for DBE (moderate vs. no pain, P=0.02), although perceived pain during the procedures was comparable (both mild, P=0.89). For future small-bowel surveillance 10/13 (77%) patients preferred DBE over MRE (P=0.09). CONCLUSIONS: Our results suggest that MRE and DBE have a comparable diagnostic yield of polyps >=15 mm. However, DBE allows for direct intervention and was preferred over MRE by most patients in this series. Larger cohorts of PJS patients are needed to fully evaluate the diagnostic yield of DBE compared with other modalities. PMID- 27404295 TI - Time for DNA Database Disclosure. PMID- 27404293 TI - Corticosteroids Versus Pentoxifylline for Severe Alcoholic Hepatitis: A Sequential Analysis of Randomized Controlled Trials. AB - INTRODUCTION: Despite the significant morbidity and mortality associated with alcoholic hepatitis, a consensus or generally accepted therapeutic strategy has not yet been reached. The purpose of this analysis was to evaluate the effects of corticosteroids and pentoxifylline on short-term mortality, incidence of hepatorenal syndrome, and sepsis in patients with severe alcoholic hepatitis. MATERIALS AND METHODS: We conducted a comprehensive search of the Cochrane library, PUBMED, Scopus, EMBASE, and published proceedings from major hepatology and gastrointestinal meetings from January 1970 to June 2015. All relevant articles irrespective of language, year of publication, type of publication, or publication status were included. Two independent reviewers extracted data and scored publications; a third investigator adjudicated discrepancies. The kappa scores were measured to assess the agreement between the 2 initial reviewers. The review and meta-analyses were performed following the recommendations of The Cochrane Collaboration. Conventional meta-analysis and Trial sequential analysis were performed. GRADEpro version 3.6 was used to appraise the quality of epidemiologic evidence. RESULTS: A total of 14 studies satisfied inclusion criteria comparing corticosteroids, pentoxifylline, or placebo. Compared with placebo, corticosteroids reduced 28-day mortality (RR=0.53; 95% CI, 0.33-0.84; P=0.006). There was no statistically significant difference in short-term mortality between pentoxifylline and placebo (RR=0.74; 95% CI, 0.46-1.18; P=0.21). Neither corticosteroids nor pentoxifylline impacted the incidence of hepatorenal syndrome or sepsis. Trial sequential analysis confirmed the results of our conventional meta-analysis. CONCLUSIONS AND RELEVANCE: Corticosteroids demonstrated a decrease in 28-day mortality in patients with severe alcoholic hepatitis. The evidence from this study is insufficient to support any recommendations regarding the mortality benefit of pentoxifylline in severe alcoholic hepatitis. PMID- 27404296 TI - Authors' Response. PMID- 27404297 TI - Regioselective and Stereospecific Dehydrogenative Annulation Utilizing Silylium Ion-Activated Alkenes. AB - Treatment of dialkylbenzylsilanes (1) with trityl tetrakis(pentafluorophenyl)borate (TPFPB) afforded the corresponding silylium ions in equilibrium with their intra- or intermolecular pi-complexes, which underwent dehydrogenative annulation with various alkenes to form 1,2,3,4 tetrahydro-2-silanaphthalenes (4) in up to 82% isolated yield. Sterically bulkier substituents on the silicon atom tended to increase the yield of cyclic products 4. The annulation products retained the stereochemistry in cases of the reactions using internal alkenes. The use of diisopropyl(1-naphthyl)silane (2) instead of 1 also resulted in annulation to obtain the 2,3-dihydro-1-sila-1H-phenalene derivatives 6. Electrophilic aromatic substitution at the 8-position was predominant, despite the two potentially reactive positions on the naphthyl group. The steric hindrance of the naphthyl group prevented addition of the cis alkene to the silylium ion, which would considerably decrease yields of the desired products from 2 compared to those from 1. PMID- 27404298 TI - Editor's notes. PMID- 27404300 TI - Running Away From Diabetes. PMID- 27404301 TI - Scanning sports. PMID- 27404303 TI - Wrap-up. PMID- 27404304 TI - Coming in sportsmedicine. PMID- 27404306 TI - Musculoskeletal Risk Factors in the Young Athlete. AB - In brief: Many children and adolescents participate in sports that put them at risk for musculoskeletal injuries. Underlying physical conditions, or risk factors, may predispose them to particular types of sports injuries. Research shows that these risk factors fall into five categories: body type, flexibility, muscle strength, inadequate rehabilitation of a previous injury, and skeletal malalignment and anomalies. Some findings show, for example, that youthful football players who are also heavy have an increased rate of injury, sprains and strains are less common in flexible athletes, and patellar pain or subluxation may be related to a variety of malalignment factors. The authors recommend using a systematic, integrated approach to risk assessment of the athlete, both for detecting risk factors and determining their potential for con tribu ting to a sports injury. PMID- 27404307 TI - Anteroinferior Tibiofibular Ligament Injury: Not Just Another Ankle Sprain. AB - In brief: Ankle sprains that primarily involve the anteroinferior tibiofibular ligament are reportedly uncommon, but the authors have recently seen several such injuries in their clinic. These high ankle sprains usually are caused by forced lateral rotation with the foot in dorsiflexion. Edema and ecchymosis are generally minimal, with pain and tenderness over the distal anterior tibiofibular syndesmosis. Pain and disability can persist for weeks. Rehabilitation consists of range-of-motion exercises leading up to weight-bearing and often takes much longer than the initial symptoms might suggest. PMID- 27404308 TI - Acute Knee Injury in Wrestling. AB - This case conference is one of a series presented at the annual meeting of the American College of Sports Medicine, Dallas, May 1988. PMID- 27404309 TI - Causes and Prevention of Injury in Downhill Skiing. AB - In brief: This literature review summarizes the current state of knowledge regarding the causes of injury in downhill skiing and discusses the incidence, distribution, risk factors, and prevention of injuries. The incidence of serious injury ranges from two to four per 1,000 ski days. About 55% of all downhill ski injuries involve the lower extremity; many of these are equipment-related. Potential risk factors fall into categories including personal characteristics, skill level, physical condition, behavior, equipment, and environment. Beginners are at higher risk, but taking lessons probably lowers the risk to some extent. Properly adjusted ski bindings undoubtedly can further lower the incidence of lower extremity injury. Similarly, improvements in the design of boots, bindings, and poles can probably make skiing safer. PMID- 27404310 TI - Injury Rates in a National Sample of College Football Teams: A 2-Year Prospective Study. AB - In brief: The National Sports Injury Surveillance System collected data during the 1986 and 1987 playing seasons from a national sample of 6,229 college football players. The overall injury rate for the two seasons was 6.32/1,000 athlete-exposures, or 45.27/100 athletes. Offensive players incurred more injuries than defensive players. The knee and ankle were the most common injury sites, and sprains were the most common injury. Injuries during games occurred most frequently in the third quarter and least often in the first quarter. This finding suggests that players might benefit from warming up and stretching during halftime rather than resting and cooling off. PMID- 27404311 TI - Managing Bursitis in the Athlete: An Overview. AB - Although conservative treatment of bursitis is fairly standard, intermediate and aggressive measures may vary substantially depending on the severity and location of bursitis. PMID- 27404312 TI - Elway's Elbow: A Case Study in Traumatic Bursitis. PMID- 27404313 TI - Chronic Brain Injury in Boxers: Is it Avoidable? AB - Short of leaving the ring altogether, the best way for a boxer to minimize risk of head injury is to limit the number of bouts he fights. But that advice is seldom heeded in the high-stakes world of boxing. PMID- 27404314 TI - Strength Training: A Bridge to Independence for the Elderly. AB - The image of an elderly person lifting weights may seem incongruous on the surface. But the fact is that strength training programs can help the elderly to remain active and independent longer-and to have a better quality of life. PMID- 27404315 TI - Opening the Airway: Equipment and Techniques. AB - When an airway is blocked, immediate action is necessary. Knowing what equipment to use and having it available can mean the difference between life and death. PMID- 27404316 TI - Meals and the Timing of Exercise. PMID- 27404318 TI - Self-Restricted Green Fluorescent Protein Chromophore Analogues: Dramatic Emission Enhancement and Remarkable Solvatofluorochromism. AB - The confinement effect of the beta-barrel defines the emission profiles of the chromophores of the green fluorescent protein (GFP) family. Here, we describe the design strategy and mimicking of confinement effects via the chromophore itself, termed the self-restricted effect. By systematically tailoring the GFP core, a family of 2,5-dialkoxy-substituted GFP chromophore analogues is found to be highly emissive and show remarkable solvatofluorochromism in fluid solvents. Fluorescence quantum yield (QY) and lifetime measurements, in combination with theoretical calculations, illustrate the mechanism relying on inhibition of torsional rotation around the exocyclic CC bond. Meanwhile, theoretical calculations further reveal that the electrostatic interaction between the solvent and the imidazolinone oxygen can contribute to suppress the radiationless decay channel around the exocyclic C?C double bond. Our findings put forward a universal approach toward unlocked highly emissive GFPc analogues, potentially promoting the understanding of the photophysics and biochemical application of GFP chromophore analogues. PMID- 27404319 TI - Optical Clearing of the Mouse Central Nervous System Using Passive CLARITY. AB - Traditionally, tissue visualization has required that the tissue of interest be serially sectioned and imaged, subjecting each tissue section to unique non linear deformations, dramatically hampering one's ability to evaluate cellular morphology, distribution and connectivity in the central nervous system (CNS). However, optical clearing techniques are changing the way tissues are visualized. These approaches permit one to probe deeply into intact organ preparations, providing tremendous insight into the structural organization of tissues in health and disease. Techniques such as Clear Lipid-exchanged Acrylamide hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) achieve this goal by providing a matrix that binds important biomolecules while permitting light scattering lipids to freely diffuse out. Lipid removal, followed by refractive index matching, renders the tissue transparent and readily imaged in 3 dimensions (3D). Nevertheless, the electrophoretic tissue clearing (ETC) used in the original CLARITY protocol can be challenging to implement successfully and the use of a proprietary refraction index matching solution makes it expensive to use the technique routinely. This report demonstrates the implementation of a simple and inexpensive optical clearing protocol that combines passive CLARITY for improved tissue integrity and 2,2'-thiodiethanol (TDE), a previously described refractive index matching solution. PMID- 27404321 TI - Electrical Detection of the Helical Spin Texture in a p-type Topological Insulator Sb2Te3. AB - The surface states of 3D topological insulators (TIs) exhibit a helical spin texture with spin locked at right angles with momentum. The chirality of this spin texture is expected to invert crossing the Dirac point, a property that has been experimentally observed by optical probes. Here, we directly determine the chirality below the Dirac point by electrically detecting spin-momentum locking in surface states of a p-type TI, Sb2Te3. A current flowing in the Sb2Te3 surface states generates a net spin polarization due to spin-momentum locking, which is electrically detected as a voltage on an Fe/Al2O3 tunnel barrier detector. Measurements of this voltage as a function of current direction and detector magnetization indicate that hole spin-momentum locking follows the right-hand rule, opposite that of electron, providing direct confirmation that the chirality is indeed inverted below Dirac point. The spin signal is linear with current, and exhibits a temperature dependence consistent with the semiconducting nature of the TI film and freeze-out of bulk conduction below 100 K. Our results demonstrate that the chirality of the helical spin texture of TI surface states can be determined electrically, an enabling step in the electrical manipulation of spins in next generation TI-based quantum devices. PMID- 27404320 TI - Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages. AB - It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies. We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we also found that ONA directly suppressed cancer cell proliferation. A combinatorial effect with ONA and anti-cancer drugs was also observed. The activation of signal transducer and activator of transcription 3 (STAT3), which is involved in cell proliferation and chemo-resistance, was significantly abrogated by ONA in ovarian cancer cells. Furthermore, the administration of ONA suppressed cancer progression and prolonged the survival time in a murine ovarian cancer model under single and combined treatment conditions. Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the protumour activation of TAMs and direct cytotoxicity against cancer cells. PMID- 27404323 TI - A climate-based prediction model in the high-risk clusters of the Mekong Delta region, Vietnam: towards improving dengue prevention and control. AB - OBJECTIVE: To develop a prediction score scheme useful for prevention practitioners and authorities to implement dengue preparedness and controls in the Mekong Delta region (MDR). METHODS: We applied a spatial scan statistic to identify high-risk dengue clusters in the MDR and used generalised linear distributed lag models to examine climate-dengue associations using dengue case records and meteorological data from 2003 to 2013. The significant predictors were collapsed into categorical scales, and the beta-coefficients of predictors were converted to prediction scores. The score scheme was validated for predicting dengue outbreaks using ROC analysis. RESULTS: The north-eastern MDR was identified as the high-risk cluster. A 1 degrees C increase in temperature at lag 1-4 and 5-8 weeks increased the dengue risk 11% (95% CI, 9-13) and 7% (95% CI, 6-8), respectively. A 1% rise in humidity increased dengue risk 0.9% (95% CI, 0.2-1.4) at lag 1-4 and 0.8% (95% CI, 0.2-1.4) at lag 5-8 weeks. Similarly, a 1 mm increase in rainfall increased dengue risk 0.1% (95% CI, 0.05-0.16) at lag 1-4 and 0.11% (95% CI, 0.07-0.16) at lag 5-8 weeks. The predicted scores performed with high accuracy in diagnosing the dengue outbreaks (96.3%). CONCLUSION: This study demonstrates the potential usefulness of a dengue prediction score scheme derived from complex statistical models for high-risk dengue clusters. We recommend a further study to examine the possibility of incorporating such a score scheme into the dengue early warning system in similar climate settings. PMID- 27404322 TI - Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction: Improving the diagnostic workup of patients with a tumor on the neck. AB - BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) often presents with cystic cervical metastasis and a small primary tumor localized in the palatine tonsils or base of the tongue, which is diagnostically challenging. Testing for HPV DNA in fine-needle aspiration (FNA) smears from metastases may facilitate a targeted diagnostic workup for identifying the primary tumor. This study was designed to assess the ability to detect HPV DNA in FNA smears with polymerase chain reaction (PCR). METHODS: May Grunvald-Giemsa (MGG)-stained FNA smears from metastases and corresponding surgical specimens were collected from 71 patients with known HPV-positive OPSCC, 12 patients with oral squamous cell carcinoma (OSCC), 20 patients with branchial cleft cysts, and 20 patients with Warthin tumors. Thirty-eight patients with OPSCC and 7 patients with OSCC had FNA smears available from metastases and also surgical specimens from the primary tumor and the metastases. The scraped cell material from FNA smears and corresponding surgical specimens were analyzed for HPV DNA by PCR. p16 immunohistochemistry was performed on surgical specimens from the carcinomas. RESULTS: HPV DNA was detected in 68 of the 71 FNA smears from OPSCC metastases. All corresponding surgical specimens from primary tumors (n = 71) and metastases (n = 38) were p16- and HPV DNA-positive. All the surgical specimens and corresponding FNA smears from OSCCs, Warthin tumors, and branchial cleft cysts were HPV DNA-negative. The sensitivity and specificity were 94.7% and 100%, respectively. CONCLUSIONS: The detection of HPV DNA in MGG-stained FNA smears by PCR is a valid method that could be implemented in routine clinical practice. Cancer Cytopathol 2016;124:820-7. (c) 2016 American Cancer Society. PMID- 27404324 TI - Seafood-Associated Shellfish Allergy: A Comprehensive Review. AB - Shellfish are diverse, serve as main constituents of seafood, and are extensively consumed globally because of their nutritional values. Consequently, increase in reports of IgE-mediated seafood allergy is particularly food associated to shellfish. Seafood-associated shellfish consists of crustaceans (decapods, stomatopods, barnacles, and euphausiids) and molluskans (gastropods, bivalves, and cephalopods) and its products can start from mild local symptoms and lead to severe systemic anaphylactic reactions through ingestion, inhalation, or contact like most other food allergens. Globally, the most commonly causative shellfish are shrimps, crabs, lobsters, clams, oysters, and mussels. The prevalence of shellfish allergy is estimated to be 0.5-2.5% of the general population but higher in coastal Asian countries where shellfish constitute a large proportion of the diet. Diversity in allergens such as tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic binding protein are from crustaceans whereas tropomyosin, paramyosin, troponin, actine, amylase, and hemoyanin are reported from molluskans shellfish. Tropomyosin is the major allergen and is responsible for cross-reactivity between shellfish and other invertebrates, within crustaceans, within molluskans, between crustaceans vs. molluskans as well as between shellfish and fish. Allergenicity diagnosis requires clinical history, in vivo skin prick testing, in vitro quantification of IgE, immunoCAP, and confirmation by oral challenge testing unless the reactions borne by it are life threatening. This comprehensive review provides the update and new findings in the area of shellfish allergy including demographic, diversity of allergens, allergenicity, their cross-reactivity, and innovative molecular genetics approaches in diagnosing and managing this life-threatening as well as life-long disease. PMID- 27404325 TI - Novel Self-shrinking Mask for Sub-3 nm Pattern Fabrication. AB - It is very difficult to realize sub-3 nm patterns using conventional lithography for next-generation high-performance nanosensing, photonic, and computing devices. Here we propose a completely original and novel concept, termed self shrinking dielectric mask (SDM), to fabricate sub-3 nm patterns. Instead of focusing the electron and ion beams or light to an extreme scale, the SDM method relies on a hard dielectric mask which shrinks the critical dimension of nanopatterns during the ion irradiation. Based on the SDM method, a linewidth as low as 2.1 nm was achieved along with a high aspect ratio in the sub-10 nm scale. In addition, numerous patterns with assorted shapes can be fabricated simultaneously using the SDM technique, exhibiting a much higher throughput than conventional ion beam lithography. Therefore, the SDM method can be widely applied in the fields which need extreme nanoscale fabrication. PMID- 27404326 TI - Can routine information from electronic patient records predict a future diagnosis of alcohol use disorder? AB - OBJECTIVE: To explore whether information regarding potentially alcohol-related health incidents recorded in electronic patient records might aid in earlier identification of alcohol use disorders. DESIGN: We extracted potentially alcohol related information in electronic patient records and tested if alcohol-related diagnoses, prescriptions of codeine, tramadol, ethylmorphine, and benzodiazepines; elevated levels of gamma-glutamyl-transferase (GGT), and mean cell volume (MCV); and new sick leave certificates predicted specific alcohol use disorder. SETTING: Nine general practitioner surgeries with varying size and stability. SUBJECTS: Totally 20,764 patients with active electronic patient record until data gathering and with a history of at least four years without a specific alcohol use disorder after turning 18 years of age. METHODS: The Cox proportional hazard analysis with time-dependent covariates of potential accumulated risks over the previous four years. MAIN OUTCOME MEASURES: Time from inclusion until the first specific alcohol use disorder, defined by either an alcohol specific diagnostic code or a text fragment documenting an alcohol problem. RESULTS: In the unadjusted and adjusted Cox-regression with time dependent covariates all variables were highly significant with adjusted hazard ratios ranging from 1.25 to 3.50. Addictive drugs, sick leaves, GGT, MCV and International Classification for Primary Care version 2 (ICPC-2), and International Classification of Diseases version 10 (ICD-10) diagnoses were analyzed. Elevated GGT and MCV, ICD-10-diagnoses, and gender demonstrated the highest hazard ratios. CONCLUSIONS: Many frequent health problems are potential predictors of an increased risk or vulnerability for alcohol use disorders. However, due to the modest hazard ratios, we were unable to establish a clinically useful tool. KEY POINTS Alcohol is potentially relevant for many health problems, but current strategies for identification and intervention in primary health care have not been successful. Many frequent clinical problems recorded in electronic patient records may indicate an increased risk for alcohol related health problems. The hazard ratios were modest and the resulting predictive model was unsatisfactory for diagnostic purposes. If we accepted a sensitivity as low as 0.50, the specificity slightly exceeded 0.75. With a low prevalent condition, it is obvious that the false positive problem will be vast. In addition to responding to elevated blood levels of liver enzymes, general practitioners should be aware of alcohol as a potentially relevant factor for patients with repeated events of many mental and psychosocial diagnoses and new sick leaves and repeated prescriptions of addictive drugs. PMID- 27404327 TI - Preparation and 3D Tracking of Catalytic Swimming Devices. AB - We report a method to prepare catalytically active Janus colloids that "swim" in fluids and describe how to determine their 3D motion using fluorescence microscopy. One commonly deployed method for catalytically active colloids to produce enhanced motion is via an asymmetrical distribution of catalyst. Here this is achieved by spin coating a dispersed layer of fluorescent polymeric colloids onto a flat planar substrate, and then using directional platinum vapor deposition to half coat the exposed colloid surface, making a two faced "Janus" structure. The Janus colloids are then re-suspended from the planar substrate into an aqueous solution containing hydrogen peroxide. Hydrogen peroxide serves as a fuel for the platinum catalyst, which is decomposed into water and oxygen, but only on one side of the colloid. The asymmetry results in gradients that produce enhanced motion, or "swimming". A fluorescence microscope, together with a video camera is used to record the motion of individual colloids. The center of the fluorescent emission is found using image analysis to provide an x and y coordinate for each frame of the video. While keeping the microscope focal position fixed, the fluorescence emission from the colloid produces a characteristic concentric ring pattern which is subject to image analysis to determine the particles relative z position. In this way 3D trajectories for the swimming colloid are obtained, allowing swimming velocity to be accurately measured, and physical phenomena such as gravitaxis, which may bias the colloids motion to be detected. PMID- 27404328 TI - The magnitude of the central visual field could be detected by active middle-late processing of ERPs. AB - This study investigated the changes in event-related potential (ERP) waveforms under different central visual field conditions using a three-stimulus oddball paradigm. Circular checkerboards were presented in the center of a computer screen with a visual angle of 5 degrees , 10 degrees , 20 degrees , or 30 degrees , which were regarded as target stimuli. The ERP waveforms were analyzed separately for different stimulus conditions. Participants responded more slowly and had lower accuracy for the 30 degrees visual field level than the other three visual field levels. The ERP results revealed that the amplitudes of target P2 gradually increased from the 5 degrees to 20 degrees visual field conditions, while they decreased abruptly in the 30 degrees visual field condition. Regional effects showed that the amplitudes of target P2 were larger from the occipital electrodes than that from the temporal sites. Besides the negative-going deflection of target N2 and visual mismatch negativity (vMMN) components having an increasing tendency with expansion of the visual field, there was also a trend that the amplitudes of target P3 were decreased and the peak latencies were prolonged with increasing visual field ranges. In addition, the latencies of the difference P3 had a similar trend to the latencies of the target P3, and all the differences were more obvious at the 30 degrees visual field level. The study demonstrated that middle-late components of ERPs can reflect changes in the visual field to some extent. PMID- 27404329 TI - A sigh of relief or a sigh to relieve: The psychological and physiological relief effect of deep breaths. AB - Both animal and human research have revealed important associations between sighs and relief. Previously we argued to conceive of sighs as resetters which temporarily induce relief. The present study aimed to investigate the psychological and physiological relief effect of sighs by instructed deep breaths and spontaneous sighs compared to a control breathing maneuver. Participants completed three blocks of 40 trials during which uncertainty cues were followed by either safety cues followed by a positive picture, or danger cues followed by a negative picture. One block was presented without breathing instructions, two subsequent blocks with breathing instructions. During the presentation of the safety and danger cues, an instruction was given to either 'take a deep breath' or 'postpone the next inhalation for 2 s (breath hold). Continuously, participants rated relief and Frontalis electromyography was recorded. Trait anxiety sensitivity was assessed by the Anxiety Sensitivity Index. Self-reported relief and physiological tension were compared 5s before and after instructed deep breaths and breath holds, and before and after spontaneous deep breaths and breath holds in the respective blocks. Results show that self-reported relief following an instructed deep breath was higher than before. Physiological tension decreased following a spontaneous sigh in high anxiety sensitive persons and following a spontaneous breath hold in low anxiety sensitive persons. These results are the first to show that a deep breath relieves and, in anxiety sensitive persons, reduces physiological tension. These findings support the hypothesis that sighs are psychological and physiological resetters. PMID- 27404330 TI - Why I'm Holding onto Hope for Nano in Oncology. PMID- 27404331 TI - Response to Dr. Thompson and Colleagues. PMID- 27404332 TI - Star-Shaped Conjugated Molecules with Oxa- or Thiadiazole Bithiophene Side Arms. AB - Star-shaped conjugated molecules, consisting of a benzene central unit symmetrically trisubstituted with either oxa- or thiadiazole bithiophene groups, were synthesized as promising molecules and building blocks for application in (opto)electronics and electrochromic devices. Their optical (Eg (opt)) as well as electrochemical (Eg (electro)) band gaps depended on the type of the side arm and the number of solubilizing alkyl substituents. Oxadiazole derivatives showed Eg (opt) slightly below 3 eV and by 0.2 eV larger than those determined for thiadiazole-based compounds. The presence of alkyl substituents in the arms additionally lowered the band gap. The obtained compounds were efficient electroluminophores in guest/host-type light-emitting diodes. They also showed a strong tendency to self-organize in monolayers deposited on graphite, as evidenced by scanning tunneling microscopy. The structural studies by X-ray scattering revealed the formation of supramolecular columnar stacks in which the molecules were organized. Differences in macroscopic alignment in the specimen indicated variations in the self-assembly mechanism between the molecules. The compounds as trifunctional monomers were electrochemically polymerized to yield the corresponding polymer network. As shown by UV/Vis-NIR spectroelectrochemical studies, these networks exhibited reversible electrochromic behavior both in the oxidation and in the reduction modes. PMID- 27404333 TI - Emerging concepts for the in vitro derivation of murine haematopoietic stem and progenitor cells. AB - Well into the second decade of the 21st century, the field of regenerative medicine is bursting with hopes and promises to heal young and old. The bespoken generation of cells is thought to offer unprecedented cures for a vast range of diseases. Haematological disorders have already benefited tremendously from stem cell therapy in the form of bone marrow transplantation. However, lack of compatible donors often means that patients remain on transplantation waiting lists for too long. The in vitro derivation of haematopoietic stem cells offers the possibility to generate tailor-made cells for the treatment of these patients. Promising approaches to generate in vitro-derived blood progenitors include the directed differentiation of pluripotent stem cells and the reprogramming of somatic cells. PMID- 27404334 TI - Comparing the Course of Mental Health Over the First Year After Stroke With Healthy Controls in Colombia, South America. AB - BACKGROUND: Stroke is a primary cause of death and disability in upper-middle income countries such as Colombia. Given the lack of comprehensive rehabilitation for stroke patients in Colombia, there is a need to assess longitudinal mental health problems poststroke in this region. OBJECTIVE: To compare the course of mental health in stroke patients to healthy controls over the first year poststroke in Ibague, Colombia. DESIGN: Cross-sectional study. SETTING: The Psychological Attention Center of Antonio Narino University in Ibague, Colombia. PARTICIPANTS: Stroke patients (n = 50) and age- and gender-matched healthy controls (n = 50). METHODS: Patients and controls completed self-report Spanish versions of demographic information, injury-related characteristics, and mental health questionnaires MAIN OUTCOME MEASUREMENTS: Outcomes assessed included mental health (depression, anxiety, and stress) at 3, 6, and 12 months poststroke. RESULTS: Hierarchical linear models suggested that stroke patients had worse depression and anxiety over time than controls (P < .001). Among patients, depression and anxiety decreased over time (P < .001), whereas stress increased over time (P < .01). The findings suggest that although anxiety and depression improved over time in stroke patients, their mental health remained significantly lower than that of controls. CONCLUSIONS: This is the first study to examine the course of mental health over the first year poststroke in Latin America, specifically in Ibague, Colombia. Despite the improvements in anxiety and depression over the first year poststroke, patient anxiety and depression were still worse in comparison to those in healthy controls. The current findings indicate a need for rehabilitation services in Colombia, especially targeting mental health issues. LEVEL OF EVIDENCE: I. PMID- 27404335 TI - Impact of Cognition on Burn Inpatient Rehabilitation Outcomes. AB - BACKGROUND: A significant proportion of burn injury patients are admitted to inpatient rehabilitation facilities (IRFs). There is increasing interest in the use of functional variables, such as cognition, in predicting IRF outcomes. Cognitive impairment is an important cause of disability in the burn injury population, yet its relationship to IRF outcomes has not been studied. OBJECTIVE: To assess how cognitive function affects rehabilitation outcomes in the burn injury population. DESIGN: Retrospective study. SETTING: Inpatient rehabilitation facilities in the United States. PARTICIPANTS: A total of 5347 adults admitted to an IRF with burn injury between 2002 and 2011. METHODS OR INTERVENTIONS: Multivariable regression was used to model rehabilitation outcome measures, using the cognitive domain of the Functional Independence Measure (FIM) instrument as the independent variable and controlling for demographic, medical, and facility covariates. MAIN OUTCOME MEASUREMENTS: FIM total gain, readmission to an acute care setting at any time during inpatient rehabilitation, readmission to an acute care setting in the first 3 days of IRF admission, rate of discharge to the community setting, and length of stay efficiency. RESULTS: Cognitive FIM total at admission was a significant predictor of FIM total gain, length of stay efficiency, and acute readmission at 3 days (P < .05). Cognitive FIM total scores did not have an impact on acute care readmission rate or discharge to the community setting. CONCLUSIONS: Cognitive status may be an important predictor of rehabilitation outcomes in the burn injury population. Future work is needed to further examine the impact of specific cognitive interventions on rehabilitation outcomes in this population. LEVEL OF EVIDENCE: II. PMID- 27404336 TI - Limited-information goodness-of-fit testing of diagnostic classification item response models. AB - Despite the growing popularity of diagnostic classification models (e.g., Rupp et al., 2010, Diagnostic measurement: theory, methods, and applications, Guilford Press, New York, NY) in educational and psychological measurement, methods for testing their absolute goodness of fit to real data remain relatively underdeveloped. For tests of reasonable length and for realistic sample size, full-information test statistics such as Pearson's X2 and the likelihood ratio statistic G2 suffer from sparseness in the underlying contingency table from which they are computed. Recently, limited-information fit statistics such as Maydeu-Olivares and Joe's (2006, Psychometrika, 71, 713) M2 have been found to be quite useful in testing the overall goodness of fit of item response theory models. In this study, we applied Maydeu-Olivares and Joe's (2006, Psychometrika, 71, 713) M2 statistic to diagnostic classification models. Through a series of simulation studies, we found that M2 is well calibrated across a wide range of diagnostic model structures and was sensitive to certain misspecifications of the item model (e.g., fitting disjunctive models to data generated according to a conjunctive model), errors in the Q-matrix (adding or omitting paths, omitting a latent variable), and violations of local item independence due to unmodelled testlet effects. On the other hand, M2 was largely insensitive to misspecifications in the distribution of higher-order latent dimensions and to the specification of an extraneous attribute. To complement the analyses of the overall model goodness of fit using M2 , we investigated the utility of the Chen and Thissen (1997, J. Educ. Behav. Stat., 22, 265) local dependence statistic XLD2 for characterizing sources of misfit, an important aspect of model appraisal often overlooked in favour of overall statements. The XLD2 statistic was found to be slightly conservative (with Type I error rates consistently below the nominal level) but still useful in pinpointing the sources of misfit. Patterns of local dependence arising due to specific model misspecifications are illustrated. Finally, we used the M2 and XLD2 statistics to evaluate a diagnostic model fit to data from the Trends in Mathematics and Science Study, drawing upon analyses previously conducted by Lee et al., (2011, IJT, 11, 144). PMID- 27404337 TI - Magnetic Nanoparticles Interaction with Humic Acid: In the Presence of Surfactants. AB - Adsorbed humic acid (HA) on surfaces of nanoparticles (NPs) will affect their transport, transfer, and fate in the aquatic environment, especially in the presence of surfactants, and thereby potentially alter exposures and bioavailable fractions of NPs and surfactants. This study investigated adsorption of HA on Fe3O4 NPs in the presence or absence of surfactant. Surfactant established a bridge connecting HA and Fe3O4 NPs, and significantly changed adsorption behavior of HA on NPs. Adsorption of HA in the absence of surfactant was 120.3 mg/g, but 350.0 mg/g and 146.5 mg/g in the present of CTAB (hexadecyl trimethylammonium bromide) and SDS (sodium dodecyl sulfate), respectively. Surfactants can form different stages (hemimicelles, mixed hemimicelles and admicelles) on Fe3O4 NPs by electrostatic and hydrophobic interactions, adsorption of HA was different for each of those stages. Adsorption of HA on surface of Fe3O4 NPs/CTAB was codetermined by hydrophobic, electrostatic interactions and ligand exchange. The presence of CTAB or SDS changed mechanisms for adsorption and effects of functional groups. Results of Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated that carbohydrate carbon was important in adsorption of HA on Fe3O4 NPs in the presence of surfactants. PMID- 27404338 TI - Icteric Vocal Cords Recorded during Video Laryngoscopy: Erratum. PMID- 27404339 TI - Radial Artery Pseudoaneurysm: A Rare Complication with Serious Risk to Life and Limb: Erratum. PMID- 27404340 TI - Influence of Magnetic Field on the Mobility of Aromatic Chiral Molecules. AB - The influence of magnetic fields on the properties of chiral molecules is of great interest nowadays. This work presents an (1)H NMR study of the mobility of 1-phenylethanol and 1-phenyl-1-propanol molecules in pure forms and in chirally polarized mixtures in external magnetic fields. Molecular mobility is shown to be dependent on the strength of the external magnetic field and chiral mixing. It could be assumed that the mobility changes are caused by rotational and magnetic interactions between induced magnetic moments of the aromatic molecules and the external magnetic field; intermolecular interactions are also essential. The results are important for the tasks related to enantiomer separation. PMID- 27404341 TI - Future Papers. PMID- 27404342 TI - Synergistically Enhanced Electrocatalytic Activity of Sandwich-like N-Doped Graphene/Carbon Nanosheets Decorated by Fe and S for Oxygen Reduction Reaction. AB - Although N-doped graphene-based electrocatalysts have shown good performance for oxygen reduction reaction (ORR), they still suffer from the single-type active site in the as-prepared catalyst, limited accessible active surface area because of easy aggregation of graphene, and harsh condition for preparation process of graphene. Therefore, further developing a novel type of graphene-based electrocatalyst by a facile and environmentally benign method is highly anticipated. Herein, we first fabricate a sandwich-like graphene/carbon hybrid using graphene oxide (GO) and nontoxic starch. Then the graphene/carbon hybrid undergoes postprocessing with iron(III) chloride (FeCl3) and potassium sulfocyanide (KSCN) to acquire N-doped graphene/carbon nanosheets decorated by Fe and S. The resultant displays the features of interpenetrated three-dimensional hierarchical architecture composed of abundant sandwich-like graphene/carbon nanosheets and low graphene content in as-prepared sample. Remarkably, the obtained catalyst possesses favorable kinetic activity due to the unique structure and synergistic effect of N, S, and Fe on ORR, showing high onset potential, low Tafel slope, and nearly four-electron pathway. Meanwhile, the catalyst exhibits strong methanol tolerance and excellent long-term durability. In view of the multiple active sites, unique hierarchical structure, low graphene content, and outstanding electrochemical activity of the as-prepared sample, this work could broaden the thinking to develop more highly efficient graphene/carbon electrocatalysts for ORR in fuel cells. PMID- 27404343 TI - Bronsted Acid-Catalyzed Cyanotritylation of Aldehydes by Trityl Isocyanide. AB - Cyanohydrins are versatile intermediates toward valuable organic compounds like alpha-hydroxy carboxylic acids, alpha-amino acids, and beta-amino alcohols. Numerous protocols are available for synthesis of (O-protected) cyanohydrins, but all procedures invariably rely on the use of toxic cyanide sources. A novel cyanide-free synthesis of O-trityl protected cyanohydrins via a catalytic Passerini-type reaction involving aldehydes and trityl isocyanide is reported. The feasibility of a catalytic asymmetric reaction is demonstrated using chiral phosphoric acid catalysis. PMID- 27404345 TI - Deficit irrigation reduces postharvest rib pinking in wholehead Iceberg lettuce, but at the expense of head fresh weight. AB - BACKGROUND: Postharvest pinking is a serious issue affecting lettuce quality. Previous studies suggested the possibility of using deficit irrigation to control discolouration; however, this approach may also affect yield. This study investigated the effect of varying irrigation deficits on iceberg lettuce (Lactuca sativa L.) to determine the relationship between irrigation deficit, pinking and fresh weight. RESULTS: The deficit imposed and head fresh weight obtained depended on both the duration and timing of withholding irrigation. Withholding irrigation for a period of 2 or 3 weeks in the middle or end of the growth period significantly reduced rib pinking compared to well-watered controls. Withholding irrigation for 2 weeks at the start of the growth period or 1 week at the end did not significantly reduce pinking. Withholding irrigation also reduced head fresh weight such that minimising pinking would be predicted to incur a loss of 40% relative to well-watered controls. However, smaller benefits to pinking reduction were achieved with less effect on head fresh weight. CONCLUSION: Deficit irrigation could be used to provide smaller but higher quality heads which are less likely to be rejected. The balance of these factors will determine the degree of adoption of this approach to growers. (c) 2016 Society of Chemical Industry. PMID- 27404344 TI - Ablation of the epithelial-specific splicing factor Esrp1 results in ureteric branching defects and reduced nephron number. AB - BACKGROUND: Abnormalities in ureteric bud (UB) branching morphogenesis lead to congenital anomalies of the kidney and reduced nephron numbers associated with chronic kidney disease (CKD) and hypertension. Previous studies showed that the epithelial fibroblast growth factor receptor 2 (Fgfr2) IIIb splice variant supports ureteric morphogenesis in response to ligands from the metanephric mesenchyme during renal organogenesis. The epithelial-specific splicing regulator Esrp1 is required for expression of Fgfr2-IIIb and other epithelial-specific splice variants. Our objective was to determine whether Esrp1 is required for normal kidney development. RESULTS: Ablation of Esrp1 in mice, alone or together with its paralog Esrp2, was associated with reduced kidney size and increased incidence of renal aplasia. Three-dimensional imaging showed that embryonic Esrp1 knockout (KO) kidneys had fewer ureteric tips and reduced nephron numbers. Analysis of alternative splicing in Esrp-null ureteric epithelial cells by RNA Seq confirmed a splicing switch in Fgfr2 as well as numerous other transcripts. CONCLUSIONS: Our findings reveal that Esrp1-regulated splicing in ureteric epithelial cells plays an important role in renal development. Defects in Esrp1 KO kidneys likely reflect reduced and/or absent ureteric branching, leading to decreased nephron induction secondary to incorrect Fgfr2 splicing and other splicing alterations. Developmental Dynamics 245:991-1000, 2016. (c) 2016 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. PMID- 27404347 TI - Corrigendum: Determining Chemically and Spatially Resolved Atomic Profile of Low Contrast Interface Structure with High Resolution. PMID- 27404348 TI - Metformin Elicits Antitumor Effects and Downregulates the Histone Methyltransferase Multiple Myeloma SET Domain (MMSET) in Prostate Cancer Cells. AB - BACKGROUND: This study explored the biological effects of metformin on prostate cancer (PCa) cells and determined molecular pathways and epigenetic regulators implicated in its mechanism of action. METHODS: We performed mRNA expression profiling in 22Rv1 cells following 2.5 mM and 5 mM metformin treatment. Genes significantly modified by metformin treatment were ranked based on altered expression, involvement with cancer-related processes, and reported dysregulation in PCa. The effects of the top ranked gene, MMSET, on the proliferative and invasive capabilities of PCa cells were investigated via siRNA knockdown alone and also combined with metformin treatment. RESULTS: Metformin treatment decreased cell growth of PCa cell line 22Rv1 and stalled cells at the G1/S checkpoint in a time- and dose-dependent manner, resulting in increased cells in G1 (P < 0.05) and decreased cells in S (P < 0.05) phase. Metformin activated the AMPK/mTOR signaling pathway as shown by increased p-AMPK and decreased p-p70S6K. mRNA expression profiling following metformin treatment identified significant changes in 136 chromatin-modifying genes. The top ranked gene, multiple myeloma SET domain (MMSET) showed increased expression in PCa cell lines (22Rv1 and DU145) when compared to the benign prostate epithelium-derived cell-line RWPE-1, and its expression was decreased upon metformin treatment. siRNA-mediated knockdown of MMSET showed decreased cellular migration and invasion in DU-145 cells. MMSET knockdown in combination with metformin treatment resulted in further reduction in the capacity of PCa cells to migrate and invade. CONCLUSIONS: These data suggest MMSET may play a role in the inhibitory effect of metformin on PCa and could serve as a potential novel therapeutic target for PCa. Prostate 76:1507-1518, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27404346 TI - A consolidated analysis of the physiologic and molecular responses induced under acid stress in the legume-symbiont model-soil bacterium Sinorhizobium meliloti. AB - Abiotic stresses in general and extracellular acidity in particular disturb and limit nitrogen-fixing symbioses between rhizobia and their host legumes. Except for valuable molecular-biological studies on different rhizobia, no consolidated models have been formulated to describe the central physiologic changes that occur in acid-stressed bacteria. We present here an integrated analysis entailing the main cultural, metabolic, and molecular responses of the model bacterium Sinorhizobium meliloti growing under controlled acid stress in a chemostat. A stepwise extracellular acidification of the culture medium had indicated that S. meliloti stopped growing at ca. pH 6.0-6.1. Under such stress the rhizobia increased the O2 consumption per cell by more than 5-fold. This phenotype, together with an increase in the transcripts for several membrane cytochromes, entails a higher aerobic-respiration rate in the acid-stressed rhizobia. Multivariate analysis of global metabolome data served to unequivocally correlate specific-metabolite profiles with the extracellular pH, showing that at low pH the pentose-phosphate pathway exhibited increases in several transcripts, enzymes, and metabolites. Further analyses should be focused on the time course of the observed changes, its associated intracellular signaling, and on the comparison with the changes that operate during the sub lethal acid-adaptive response (ATR) in rhizobia. PMID- 27404349 TI - DNA Topoisomerase IIalpha contributes to the early steps of adipogenesis in 3T3 L1 cells. AB - DNA topoisomerases (Topo) are multifunctional enzymes resolving DNA topological problems such as those arising during DNA replication, transcription and mitosis. Mammalian cells express 2 class II isoforms, Topoisomerases IIalpha (Topo IIalpha) and IIbeta (Topo IIbeta), which have similar enzymatic properties but are differently expressed, in dividing and pluripotent cells, and in post-mitotic and differentiated cells respectively. Pre-adipocytes re-enter the cell cycle prior to committing to their differentiation and we hypothesised that Topo II could contribute to these processes. We show that Topo IIalpha expression in 3T3 L1 cells is induced within 16h after the initiation of the differentiation programme, peaks at 24h and rapidly declines thereafter. In contrast Topo IIbeta was present both in pre-adipocytes and throughout differentiation. Inhibition of PI3K with LY294002, known to prevent adipocyte differentiation, consistently reduced the expression of Topo IIalpha, whereas a clear effect on Topo IIbeta was not apparent. In addition, inhibition of mTOR with rapamycin also reduced the protein levels of Topo IIalpha. Using specific class IA PI3K catalytic subunit inhibitors, we show that p110alpha inhibition with A66 has the greatest reduction of Topo IIalpha expression and of differentiation, as measured by triglyceride storage. The timing of Topo IIalpha expression coincides with the mitotic clonal expansion (MCE) phase of differentiation and inhibition of Topo II with ICRF-187 during this stage decreased PPARgamma1 and 2 protein levels and triglyceride storage, whereas inhibition later on has little impact. Moreover, the addition of ICRF-187 had no effect on the incorporation of EdU during S-phase at day 1 but lowered the relative cell numbers on day 2. ICRF-187 also induced an increase in the centri/pericentromeric heterochromatin localisation of Topo IIalpha, indicating a role for Topo IIalpha at these locations during MCE. In summary, we present evidence that Topo IIalpha plays an important role in adipogenesis during MCE and in a PI3K/mTOR-dependent manner. Considering that Topoisomerases II are targets in cancer chemotherapy, our results highlight that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. PMID- 27404350 TI - Tissue Sculpting by Fibrils. AB - In this issue of Developmental Cell, Isabella and Horne-Badovinac (2016) show that Rab10 directs site-specific secretion of basement membrane components, which assemble into fibrils that spool out to elongate the Drosophila egg chamber. These findings establish the basement membrane's active role in tissue sculpting. PMID- 27404351 TI - A Pluripotency Platform for Prdm14. AB - The tripartite network of Prdm14, Blimp1, and AP2gamma is essential for the important process of germ cell specification, but their precise molecular mechanisms of action remain lacking. Tu and colleagues (2016) report in Nature that the transcriptional co-repressor CBFA2T2 is an essential interactor protein regulating PRDM14 function, shedding light into the mechanisms directing germline formation and pluripotency. PMID- 27404352 TI - Right Place Right Time: Heterogeneity-Driven Organ Geometry. AB - How do plants make species-specific leaves and flowers with stereotypical size and shape? A new study in Developmental Cell finds that local spatiotemporal variability in cell growth rate is essential for robustness in organ geometry control, and reactive oxygen species act to suppress this local heterogeneity during organ maturation. PMID- 27404353 TI - Germ Cells Need Folate to Proliferate. AB - In this issue of Developmental Cell, Chaudhari and colleagues (2016) use a novel method to create an in vitro proliferative cell line from tumorous C. elegans germ cells, and in the process discover that bacterial folates act as signals for proliferation, independent of their roles as vitamins. PMID- 27404354 TI - Taking Centrioles to the Elimination Round. AB - Two recent papers published in The Journal of Cell Biology (Borrego-Pinto et al., 2016) and Science (Pimenta-Marques et al., 2016) have begun to shed light on the mechanism of centriole elimination during female oogenesis, highlighting a protective role for Polo kinase and the pericentriolar material. PMID- 27404355 TI - Patronin Takes a Shot at Polarity. AB - To specify the anterior-posterior axis of Drosophila embryos, noncentrosomal microtubules grow out from cortical regions of the oocyte and help transport axis determinants. In this issue of Developmental Cell, Nashchekin et al. (2016) report a Shot- and Patronin-dependent mechanism by which the oocyte cortex produces polarized microtubule arrays. PMID- 27404356 TI - Variable Cell Growth Yields Reproducible OrganDevelopment through Spatiotemporal Averaging. AB - Organ sizes and shapes are strikingly reproducible, despite the variable growth and division of individual cells within them. To reveal which mechanisms enable this precision, we designed a screen for disrupted sepal size and shape uniformity in Arabidopsis and identified mutations in the mitochondrial i-AAA protease FtsH4. Counterintuitively, through live imaging we observed that variability of neighboring cell growth was reduced in ftsh4 sepals. We found that regular organ shape results from spatiotemporal averaging of the cellular variability in wild-type sepals, which is disrupted in the less-variable cells of ftsh4 mutants. We also found that abnormal, increased accumulation of reactive oxygen species (ROS) in ftsh4 mutants disrupts organ size consistency. In wild type sepals, ROS accumulate in maturing cells and limit organ growth, suggesting that ROS are endogenous signals promoting termination of growth. Our results demonstrate that spatiotemporal averaging of cellular variability is required for precision in organ size. PMID- 27404357 TI - Bacterial Folates Provide an Exogenous Signal for C. elegans Germline Stem Cell Proliferation. AB - Here we describe an in vitro primary culture system for Caenorhabditis elegans germline stem cells. This culture system was used to identify a bacterial folate as a positive regulator of germ cell proliferation. Folates are a family of B complex vitamins that function in one-carbon metabolism to allow the de novo synthesis of amino acids and nucleosides. We show that germ cell proliferation is stimulated by the folate 10-formyl-tetrahydrofolate-Glun both in vitro and in animals. Other folates that can act as vitamins to rescue folate deficiency lack this germ cell stimulatory activity. The bacterial folate precursor dihydropteroate also promotes germ cell proliferation in vitro and in vivo, despite its inability to promote one-carbon metabolism. The folate receptor homolog FOLR-1 is required for the stimulation of germ cells by 10-formyl tetrahydrofolate-Glun and dihydropteroate. This work defines a folate and folate related compound as exogenous signals to modulate germ cell proliferation. PMID- 27404358 TI - Rab10-Mediated Secretion Synergizes with Tissue Movement to Build a Polarized Basement Membrane Architecture for Organ Morphogenesis. AB - Basement membranes (BMs) are planar protein networks that support epithelial function. Regulated changes to BM architecture can also contribute to tissue morphogenesis, but how epithelia dynamically remodel their BMs is unknown. In Drosophila, elongation of the initially spherical egg chamber correlates with the generation of a polarized network of fibrils in its surrounding BM. Here, we use live imaging and genetic manipulations to determine how these fibrils form. BM fibrils are assembled from newly synthesized proteins in the pericellular spaces between the egg chamber's epithelial cells and undergo oriented insertion into the BM by directed epithelial migration. We find that a Rab10-based secretion pathway promotes pericellular BM protein accumulation and fibril formation. Finally, by manipulating this pathway, we show that BM fibrillar structure influences egg chamber morphogenesis. This work highlights how regulated protein secretion can synergize with tissue movement to build a polarized BM architecture that controls tissue shape. PMID- 27404359 TI - Patronin/Shot Cortical Foci Assemble the Noncentrosomal Microtubule Array that Specifies the Drosophila Anterior-Posterior Axis. AB - Noncentrosomal microtubules play an important role in polarizing differentiated cells, but little is known about how these microtubules are organized. Here we identify the spectraplakin, Short stop (Shot), as the cortical anchor for noncentrosomal microtubule organizing centers (ncMTOCs) in the Drosophila oocyte. Shot interacts with the cortex through its actin-binding domain and recruits the microtubule minus-end-binding protein, Patronin, to form cortical ncMTOCs. Shot/Patronin foci do not co-localize with gamma-tubulin, suggesting that they do not nucleate new microtubules. Instead, they capture and stabilize existing microtubule minus ends, which then template new microtubule growth. Shot/Patronin foci are excluded from the oocyte posterior by the Par-1 polarity kinase to generate the polarized microtubule network that localizes axis determinants. Both proteins also accumulate apically in epithelial cells, where they are required for the formation of apical-basal microtubule arrays. Thus, Shot/Patronin ncMTOCs may provide a general mechanism for organizing noncentrosomal microtubules in differentiated cells. PMID- 27404360 TI - Monoubiquitination of Syntaxin 5 Regulates Golgi Membrane Dynamics during the Cell Cycle. AB - The Golgi apparatus undergoes a ubiquitin-dependent disassembly and reassembly process during each cycle of cell division. Here we report the identification of the Golgi t-SNARE syntaxin 5 (Syn5) as the ubiquitinated substrate. Syn5 is monoubiquitinated by the ubiquitin ligase HACE1 in early mitosis and deubiquitinated by the deubiquitinase VCIP135 in late mitosis. Syn5 ubiquitination on lysine 270 (K270) in the SNARE domain impairs the interaction between Syn5 and the cognate v-SNARE Bet1 but increases its binding to p47, the adaptor protein of p97. Expression of the Syn5 K270R mutant in cells impairs post mitotic Golgi reassembly. Therefore, monoubiquitination of Syn5 in early mitosis disrupts SNARE complex formation. Subsequently, ubiquitinated Syn5 recruits p97/p47 to the mitotic Golgi fragments and promotes post-mitotic Golgi reassembly upon ubiquitin removal by VCIP135. Overall, this study reveals both the substrate and the mechanism of ubiquitin-mediated regulation of Golgi membrane dynamics during the cell cycle. PMID- 27404361 TI - The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes. AB - Autophagosome formation in yeast entails starvation-induced assembly of the pre autophagosomal structure (PAS), in which multiple Atg1 complexes (composed of Atg1, Atg13, and the Atg17-Atg29-Atg31 subcomplex) are initially engaged. However, the molecular mechanisms underlying the multimeric assembly of these complexes remain unclear. Using structural and biological techniques, we herein demonstrate that Atg13 has a large intrinsically disordered region (IDR) and interacts with two distinct Atg17 molecules using two binding regions in the IDR. We further reveal that these two binding regions are essential not only for Atg1 complex assembly in vitro, but also for PAS organization in vivo. These findings underscore the structural and functional significance of the IDR of Atg13 in autophagy initiation: Atg13 provides intercomplex linkages between Atg17-Atg29 Atg31 complexes, thereby leading to supramolecular self-assembly of Atg1 complexes, in turn accelerating the initial events of autophagy, including autophosphorylation of Atg1, recruitment of Atg9 vesicles, and phosphorylation of Atg9 by Atg1. PMID- 27404362 TI - Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene Expression Analysis Informs Induction of Naive Pluripotency. AB - Human preimplantation embryo development involves complex cellular and molecular events that lead to the establishment of three cell lineages in the blastocyst: trophectoderm, primitive endoderm, and epiblast. Owing to limited resources of biological specimens, our understanding of how the earliest lineage commitments are regulated remains narrow. Here, we examined gene expression in 241 individual cells from early and late human blastocysts to delineate dynamic gene-expression changes. We distinguished all three lineages and further developed a 3D model of the inner cell mass and trophectoderm in which individual cells were mapped into distinct expression domains. We identified in silico precursors of the epiblast and primitive endoderm lineages and revealed a role for MCRS1, TET1, and THAP11 in epiblast formation and their ability to induce naive pluripotency in vitro. Our results highlight the potential of single-cell gene-expression analysis in human preimplantation development to instruct human stem cell biology. PMID- 27404363 TI - Tropheryma whipplei associated with diarrhoea in young children. AB - Tropheryma whipplei was detected in preliminary studies in faeces of young children with diarrhoea and also in faeces of asymptomatic persons, not only in Europe but also in Africa. In this study, the link between this bacterium and the presence of acute diarrhoea was evaluated in a large group of children. From December 2009 to January 2013, rectal swabs collected from 3796 children in the emergency departments of university hospitals in Marseille, France, were analysed: 555 children (245 female and 310 male, from 6 days to 6 years old) with acute diarrhoea defined as at least three loose stools per day for <1 week and 3241 children (1444 female and 1797 male, from 22 days to 6 years old) without diarrhoea. Specific quantitative real-time PCR was performed to detect the presence of T. whipplei and of two enteric pathogens Clostridium difficile and Giardia duodenalis. Tropheryma whipplei was significantly more common in children with diarrhoea (22/555, 4%) than without (56/3241, 1.7%; p 0.001). Neither C. difficile nor G. duodenalis showed this association. For C. difficile, 39 of 531 (7.3%) children with diarrhoea were positive versus 184 of 3119 (5.9%) of children without diarrhoea (p 0.25). For G. duodenalis, 2 of 529 (0.37%) children with diarrhoea were positive versus 5 of 3119 (0.16%) children without diarrhoea (p 0.26). Tropheryma whipplei was found more commonly in autumn. Tropheryma whipplei is significantly associated with diarrhoea in children, suggesting that the bacterium may be a cause of acute diarrhoea. PMID- 27404364 TI - Why should 1 gram of ceftriaxone monotherapy be considered as a therapeutic option in gonococcal sexually transmitted diseases? PMID- 27404365 TI - The optimization and validation of the Biotyper MALDI-TOF MS database for the identification of Gram-positive anaerobic cocci. AB - Gram-positive anaerobic cocci (GPAC) account for 24%-31% of the anaerobic bacteria isolated from human clinical specimens. At present, GPAC are under represented in the Biotyper MALDI-TOF MS database. Profiles of new species have yet to be added. We present the optimization of the matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) database for the identification of GPAC. Main spectral profiles (MSPs) were created for 108 clinical GPAC isolates. Identity was confirmed using 16S rRNA gene sequencing. Species identification was considered to be reliable if the sequence similarity with its closest relative was >=98.7%. The optimized database was validated using 140 clinical isolates. The 16S rRNA sequencing identity was compared with the MALDI-TOF MS result. MSPs were added from 17 species that were not yet represented in the MALDI-TOF MS database or were under-represented (fewer than five MSPs). This resulted in an increase from 53.6% (75/140) to 82.1% (115/140) of GPAC isolates that could be identified at the species level using MALDI-TOF MS. An improved log score was obtained for 51.4% (72/140) of the strains. For strains with a sequence similarity <98.7% with their closest relative (n = 5) or with an inconclusive sequence identity (n = 4), no identification was obtained by MALDI-TOF MS or in the latter case an identity with one of its relatives. For some species the MSP of the type strain was not part of the confined cluster of the corresponding clinical isolates. Also, not all species formed a homogeneous cluster. It emphasizes the necessity of adding sufficient MSPs of human clinical isolates. PMID- 27404367 TI - Molecular quantification of bacteria from respiratory samples in patients with suspected ventilator-associated pneumonia. AB - Ventilator-associated pneumonia (VAP) is the most common infection in critically ill patients. Initial antibiotic therapy is often broad spectrum, which promotes antibiotic resistance so new techniques are under investigation to obtain early microbiological identification and quantification. This trial compares the performance of a new real-time quantitative molecular-based method with conventional culture in patients with suspected VAP. Patients with suspected VAP who were ventilated for at least 48 h were eligible. An endotracheal aspirate (ETA) and a bronchoalveolar lavage (BAL) were performed at each suspected VAP episode. Both samples were analysed by conventional culture and molecular analysis. For the latter, bacterial DNA was extracted from each sample and real time PCR were run. In all, 120 patients were finally included; 76% (91) were men; median age was 65 years, and clinical pulmonary infection score was >=6 for 73.5% (86) of patients. A total of 120 BAL and 103 ETA could be processed and culture results above the agreed threshold were obtained for 75.0% (90/120) of BAL and 60.2% (62/103) of ETA. The main isolated bacteria were Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae. Performance was 89.2% (83.2% 93.6%) sensitivity and 97.1% (96.1%-97.9%) specificity for BAL samples and 71.8% (61.0%-81.0%) sensitivity and 96.6% (95.4%-97.5%) specificity for ETA samples when the molecular biology method was compared with conventional culture method (chosen as reference standard). This new molecular method can provide reliable quantitative microbiological data and is highly specific with good sensitivity for common pathogens involved in VAP. PMID- 27404366 TI - Pregnancy outcomes and cytomegalovirus DNAaemia in HIV-infected pregnant women with CMV. PMID- 27404368 TI - High rate of faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in healthy children in Bangui, Central African Republic. AB - The aim of this study was to estimate the prevalence of extended-spectrum beta lactamase-producing Enterobacteriaceae (ESBL-E) in faeces of healthy children aged 0-59 months in Bangui (Central African Republic). Stool samples of 134 children, recruited for a matched case-control study, were cultured on a commercial ESBL-selective chromogenic medium (CHROMagar ESBL, France). The phenotypic resistance patterns of isolated strains were investigated, as well as the genetic basis for antibiotic resistance. The factors associated with increased risk for ESBL-E carriage were also studied. The prevalence of ESBL-E carriage was 59% (79/134), one of the highest reported worldwide. The only factor found to be associated with carriage was living in a highest-income family (p=0.03). In all, 83 ESBL-E were recovered as simultaneous carriage of two strains was detected in four children. blaCTX-M-15 was found in all strains except two, frequently associated with qnr (54/81, 66%) and aac(6')-Ib-cr (35/81, 43%) genes. Escherichia coli, the most commonly recovered species (51/83, 61%), was assigned mainly to the pandemic B2-O25b-ST131 group (39/51, 76%). Resistance transfer, which was studied in 20 randomly selected ESBL-E strains, was successful in 13 (13/20, 65%) isolates. In eight of these isolates (8/13, 62%), blaCTX-M-15 genes were found in incompatibility group FIb conjugative plasmids. We found one of the highest prevalence rates of faecal carriage of ESBL-E reported worldwide, highlighting the need to improve control of the distribution of antibiotics in limited-resource countries. PMID- 27404369 TI - Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV6. PMID- 27404370 TI - Betamethasone and dexamethasone in adult community-acquired bacterial meningitis: a quality registry study from 1995 to 2014. AB - Acute bacterial meningitis (ABM) is a highly lethal disease. Available data support the use of corticosteroids in high-income countries, but the effect on mortality is still controversial. The effects of corticosteroids on mortality and sequelae were evaluated in the national Swedish quality registry. In total, during 1995-2014 1746 adults with ABM were included, of whom 989 were treated with corticosteroids (betamethasone, n = 766; dexamethasone, n = 248; methylprednisolone, n = 2), 498 were not given corticosteroids and in 259 patients data for corticosteroids were missing. Fatal outcome was observed in 8.9% of the patients in the corticosteroid-treated group vs. 17.9% in the non corticosteroid-treated group (p <0.001), resulting in an odds ratio (OR) of 0.57 with a 95% confidence interval (CI) of 0.40-0.81 adjusted for age, sex, mental status, and door-to-antibiotic time. In patients with meningitis caused by S. pneumoniae, mortality was 10.2% in the corticosteroid-treated group and 21.3% in the non-corticosteroid-treated group (p <0.001) with an adjusted OR of 0.50 (95% CI 0.31-0.80). In ABM patients with non-pneumococcal aetiology the adjusted OR was 0.71 (95% CI 0.40-1.26). Lower mortality was observed in the corticosteroid treated group with impaired mental status, whereas no significant difference was found in patients with unaffected mental status. The adjusted ORs for betamethasone and dexamethasone were 0.49 (95% CI 0.28-0.84) and 0.61 (95% CI 0.37-1.01), respectively. Corticosteroid treatment decreases mortality in ABM and should be administered initially with antibiotics in adult ABM patients with impaired mental status regardless of presumed aetiology. Betamethasone seems to be at least as effective as dexamethasone. PMID- 27404372 TI - Emerging diseases-the monkeypox epidemic in the Democratic Republic of the Congo. PMID- 27404371 TI - The contribution of the European high containment laboratories during the 2014 2015 Ebola Virus Disease emergency. PMID- 27404373 TI - Feasibility of hybrid off pump artery bypass grafting and transaortic transcatheter aortic valve implantation: A case series. AB - INTRODUCTION: Patients with complex coronary artery disease and severe aortic stenosis unsuitable for conventional cardiac surgery pose a significant treatment challenge. This is especially difficult for patients where percutaneous revascularization is technically very challenging and/or would not offer as complete revascularisation compared to surgical revascularisation. In addition, patients who are unsuitable for transfemoral transcatheter aortic valve implantation (TAVI) pose an additional technical challenge, particularly with dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI). As a potential solution we describe the first case series of hybrid off pump coronary artery bypass grafting (CABG) combined with transaortic TAVI. METHODS AND RESULTS: Over a ten-month-period, four patients underwent hybrid off pump CABG combined with transaortic TAVI. A full sternotomy allowed off-pump arterial and vein graft anastomosis to significantly stenosed coronaries. The first three patients had severe aorto-iliac disease precluding femoral access; the fourth patient was deemed unsuitable for PCI. Transaortic TAVI using Edwards Sapien 3 valves were performed without complication in all four patients. CONCLUSION: The hybrid off-pump CABG and transaortic TAVI procedure allows for more complete coronary revascularization, negates the need for DAPT, and minimizes treatment delay of a TAVI procedure, particularly in patients unsuitable for transfemoral access. We propose this as an important treatment option for the heart team to consider. (c) 2016 Wiley Periodicals, Inc. PMID- 27404374 TI - Development and validation of a generic high-performance liquid chromatography for the simultaneous separation and determination of six cough ingredients: Robustness study on core-shell particles. AB - A generally applicable high-performance liquid chromatographic method for the qualitative and quantitative determination of pharmaceutical preparations containing phenylephrine hydrochloride, paracetamol, ephedrine hydrochloride, guaifenesin, doxylamine succinate, and dextromethorphan hydrobromide is developed. Optimization of chromatographic conditions was performed for the gradient elution using different buffer pH values, flow rates and two C18 stationary phases. The method was developed using a Kinetex(r) C18 column as a core-shell stationary phase with a gradient profile using buffer pH 5.0 and acetonitrile at 2.0 mL/min flow rate. Detection was carried out at 220 nm and linear calibrations were obtained for all components within the studied ranges. The method was fully validated in agreement with ICH guidelines. The proposed method is specific, accurate and precise (RSD% < 3%). Limits of detection are lower than 2.0 MUg/mL. Qualitative and quantitative responses were evaluated using experimental design to assist the method robustness. The method was proved to be highly robust against 10% change in buffer pH and flow rate (RSD% < 10%), however, the flow rate may significantly influence the quantitative responses of phenylephrine, paracetamol, and doxylamine (RSD% > 10%). Satisfactory results were obtained for commercial combinations analyses. Statistical comparison between the proposed chromatographic and official methods revealed no significant difference. PMID- 27404375 TI - A prospective comparative study of channel photoselective vaporization of the prostate vs. channel transurethral resection of the prostate in patients with advanced prostate carcinoma. AB - BACKGROUND: To compare short-term efficacy and safety of channel photoselective vaporization of prostate (PVP) and channel transurethral resection of prostate (TURP) in patients with bladder outlet obstruction (BOO) secondary to advanced carcinoma prostate. METHODS: This prospective, non-randomized comparative study was conducted between April 2012 and December 2014. Patients with locally advanced/metastatic carcinoma prostate, who underwent either channel PVP or channel TURP for troublesome LUTS/ acute retention of urine were included in the study. Preoperative, intraoperative, postoperative and follow up data at 1, 3 and 6 months was recorded for analysis. RESULTS: Data analysis of 34 and 37 patients, who underwent channel PVP and channel TURP respectively, were performed. Baseline characteristics of the two groups were similar with no statistical difference noted between them. Though the operative duration was significantly higher in channel PVP group; perioperative blood loss, need for postoperative irrigation, duration of postoperative irrigation and catheterization were significantly lesser compared to channel TURP group. Clot retention rates were significantly higher in channel TURP group. The efficacy parameters were comparable between the two groups at 6 months' follow-up. CONCLUSIONS: Channel KTP-PVP is an efficacious alternative to channel TURP in the management of BOO secondary to advanced carcinoma prostate with the added advantages of significantly less perioperative blood loss, no requirement for blood transfusion and a short catheterization time. PMID- 27404376 TI - Urothelial carcinoma of the upper urinary tracts: current knowledge and future perspectives. PMID- 27404377 TI - Categorical Perception Beyond the Basic Level: The Case of Warm and Cool Colors. AB - Categories can affect our perception of the world, rendering between-category differences more salient than within-category ones. Across many studies, such categorical perception (CP) has been observed for the basic-level categories of one's native language. Other research points to categorical distinctions beyond the basic level, but it does not demonstrate CP for such distinctions. Here we provide such a demonstration. Specifically, we show CP in English speakers for the non-basic distinction between "warm" and "cool" colors, claimed to represent the earliest stage of color lexicon evolution. Notably, the advantage for discriminating colors that straddle the warm-cool boundary was restricted to the right visual field-the same behavioral signature previously observed for basic level categories. This pattern held in a replication experiment with increased power. Our findings show that categorical distinctions beyond the basic-level repertoire of one's native language are psychologically salient and may be spontaneously accessed during normal perceptual processing. PMID- 27404378 TI - Inhomogeneous distribution of Iba-1 characterizes microglial pathology in Alzheimer's disease. AB - Microglial dystrophy has recently been described as a morphological phenotype of microglia that differs from resting and activated states by spheroid formation and cytorrhexis. In thick sections immunolabeled for HLA-DR or Iba-1 dystrophic microglial processes lose their typical, homogeneous staining pattern and appear to be fragmented or clustered. In this study, we performed double immunofluorescence and electron microscopy to determine if this labeling pattern indeed reflects complete separation of microglial processes from the soma. Using Iba-1/CD68 and Iba-1/MHC class II, as microglial markers, we observed that isolated Iba-1 fragments were still connected to each other by segments of the microglial process immune positive for CD68 or MHC class II. Ultrathin serial sections of two Iba-1 fragments which appeared to be disconnected from each other at the light microscopical level revealed a still existing "bridge" with a diameter of around 0.182 um. Therefore, microglial dystrophy may reflect alterations of the cytoskeleton ultimately leading to slow cytorrhexis. GLIA 2016;64:1562-1572. PMID- 27404380 TI - Surgical prevention of epithelial ovary cancer without oophorectomy: changing the future. PMID- 27404379 TI - Low Prevalence of Ocular Chlamydia trachomatis Infection and Active Trachoma in the Western Division of Fiji. AB - BACKGROUND: Trachoma is the leading infectious cause of blindness and is caused by ocular infection with the bacterium Chlamydia trachomatis (Ct). While the majority of the global disease burden is found in sub-Saharan Africa, the Western Pacific Region has been identified as trachoma endemic. Population surveys carried out throughout Fiji have shown an abundance of both clinically active trachoma and trachomatous trichiasis in all divisions. This finding is at odds with the clinical experience of local healthcare workers who do not consider trachoma to be highly prevalent. We aimed to determine whether conjunctival infection with Ct could be detected in one administrative division of Fiji. METHODS: A population-based survey of 2306 individuals was conducted using the Global Trachoma Mapping Project methodology. Population prevalence of active trachoma in children and trichiasis in adults was estimated using the World Health Organization simplified grading system. Conjunctival swabs were collected from 1009 children aged 1-9 years. DNA from swabs was tested for the presence of the Ct plasmid and human endogenous control. RESULTS: The prevalence of active trachoma in 1-9 year olds was 3.4%. The age-adjusted prevalence was 2.8% (95% CI: 1.4-4.3%). The unadjusted prevalence of ocular Ct infection in 1-9 year-olds was 1.9% (19/1009), and the age-adjusted infection prevalence was 2.3% (95% CI: 0.4 2.5%). The median DNA load was 41 Ct plasmid copies per swab (min 20, first quartile 32, mean 6665, third quartile 161, max 86354). There was no association between current infection and follicular trachoma. No cases of trachomatous trichiasis were identified. DISCUSSION: The Western Division of Fiji has a low prevalence of clinical trachoma. Ocular Ct infections were observed, but they were predominantly low load infections and were not correlated with clinical signs. Our study data suggest that trachoma does not meet the WHO definition of a public health problem in this Division of Fiji, but the inconsistency with previous studies warrants further investigation. PMID- 27404382 TI - Endothelial cell alignment as a result of anisotropic strain and flow induced shear stress combinations. AB - Endothelial cells (ECs) are continuously exposed in vivo to cyclic strain and shear stress from pulsatile blood flow. When these stimuli are applied in vitro, ECs adopt an appearance resembling their in vivo state, most apparent in their alignment (perpendicular to uniaxial strain and along the flow). Uniaxial strain and flow perpendicular to the strain, used in most in vitro studies, only represent the in vivo conditions in straight parts of vessels. The conditions present over large fractions of the vasculature can be better represented by anisotropic biaxial strains at various orientations to flow. To emulate these biological complexities in vitro, we have developed a medium-throughput device to screen for the effects on cells of variously oriented anisotropic biaxial strains and flow combinations. Upon the application of only strains for 24 h, ECs (HUVECs) aligned perpendicular to the maximum principal strain and the alignment was stronger for a higher maximum:minimum principal strain ratio. A 0.55 Pa shear stress, when applied alone or with strain for 24 h, caused cells to align along the flow. Studying EC response to such combined physiological mechanical stimuli was not possible with existing platforms and to our best knowledge, has not been reported before. PMID- 27404381 TI - Identification of Specific miRNA Signature in Paired Sera and Tissue Samples of Indian Women with Triple Negative Breast Cancer. AB - Of several subtypes of breast cancer, triple negative breast cancer (TNBC) is a highly aggressive tumor that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor receptor 2 and shows a worst prognosis. The small noncoding RNAs (miRNAs) considered as master regulator of gene expression play a key role in cancer initiation, progression and drug resistance and have emerged as attractive molecular biomarkers for diagnosis, prognosis and treatment targets in cancer. We have done expression profiling of selected miRNAs in paired serum and tissue samples of TNBC patients and corresponding cell lines and compared with that of other subtypes, in order to identify novel serum miRNA biomarkers for early detection and progression of TNBC. A total of 85 paired tumor tissues and sera with an equal number of adjacent normal tissue margins and normal sera from age matched healthy women including tissue and sera samples from 15 benign fibroadenomas were employed for the study. We report for the first time an extremely high prevalence (73.9%) of TNBC in premenopausal women below 35 years of age and a significant altered expression of a panel of three specific oncogenic miRNAs- miR-21, miR-221, miR 210, and three tumor suppressor miRNAs- miR-195, miR-145 and Let-7a in both tissues and corresponding sera of TNBC patients when compared with triple positive breast cancer (TPBC) patients. While miR-21, miR-221 and miR-210 showed significant over-expression, miR-195 and miR-145 were downregulated and well correlated with various clinicopathological and demographic risk factors, tumor grade, clinical stage and hormone receptor status. Interestingly, despite being a known tumor suppressor, Let-7a showed a significant overexpression in TNBCs. It is suggested that this panel of six miRNA signature may serve as a minimally invasive biomarker for an early detection of TNBC patients. PMID- 27404383 TI - Inverse focusing inside turbid media by creating an opposite virtual objective. AB - Limited by the penetration depth, imaging of thick bio-tissues can be achieved only by epi-detection geometry. Applications based on forward-emitted signals or bidirectional illumination are restricted by lack of an opposite objective. A method for creating an opposite virtual objective inside thick media through phase conjugation was first proposed. Under forward illumination, the backward scattering light from the media was collected to generate a phase conjugate wave, which was sent back to the media and formed an inverse focusing light. Samples combined with a diffuser or a mouse skin were used as specimens. Inverse focusing was successfully demonstrated by applying holography-based optical phase conjugation with a BaTiO3. This result indicates the capability to create an opposite virtual objective inside live tissues. The proposed method is compatible with current coherent imaging and super-resolution imaging technologies. It creates a possible way for forward-emitted signals collection and bidirectional illumination in thick specimens. PMID- 27404384 TI - Clinical Application of Multicolor Imaging Technology. AB - PURPOSE: To assess the clinical application of multicolor imaging by confocal scanning laser ophthalmoscopy (cSLO). METHODS: Retinal imaging was performed in 76 patients including cSLO multicolor imaging (SPECTRALIS SD-OCT, Heidelberg Engineering, Heidelberg, Germany) and color fundus photography (CFP). RESULTS: The use of confocal optics, reduced light scatter and automated eye tracking enable high-resolution cSLO reflectance images. Compared to CFP, the appearance of pigment alterations and hemorrhages were some of the differences observed. Various artifacts including those derived from optical media alterations need to be considered when interpreting images. Specific pathological findings including epiretinal membranes, fibrovascular proliferations, and reticular pseudodrusen may be better visualized on multicolor images. CONCLUSIONS: When using multicolor imaging, ophthalmologists need to be mindful about differences in the appearance of pathological changes and artifacts. Multicolor imaging may offer information over and above conventional CFP; it can be performed through undilated pupils and is less affected by media opacities. PMID- 27404385 TI - Isolation of Mouse Coronary Endothelial Cells. AB - Endothelial cells line the inner wall of blood vessels and play an important role in the regulation of vascular tone, vascular permeability, and new vascular formation. Endothelial cell dysfunction is implicated in the development and progression of many cardiovascular diseases including ischemic heart disease. To examine the function and characterization of coronary endothelial cells, cell isolation is the first step and it requires high purity and quantity to conduct subsequent experiments. This protocol describes an efficient method to isolate adult mouse coronary endothelial cells. The mouse heart is dissected and minced into small pieces. After the digestion of the heart using dispase and collagenase II, cells are washed and incubated with magnetic beads which are conjugated with anti-CD31 antibody. The beads with endothelial cells are washed several times and are ready to use in various applications, including imaging and molecular biological experiments. Efficient isolation yields approximately 10(4) cells per one heart with over 90% purity. PMID- 27404386 TI - Seasonal Timing of Infant Bronchiolitis, Apnea and Sudden Unexplained Infant Death. AB - Rates of Sudden Unexplained Infant Death (SUID), bronchiolitis, and central apnea increase in winter in temperate climates. Though associations between these three conditions are suggested, more work is required to establish if there is a causal pathway linking bronchiolitis to SUID through inducing central apnea. Utilizing a large population-based cohort of infants studied over a 20-year period (n = 834,595, from birth years 1989-2009)), we analyzed ecological associations between timing of SUID cases, bronchiolitis, and apnea healthcare visits. Data were analyzed between 2013 and 2015. We used a Cox Proportional Hazards model to analyze possible interactions between maternal smoking and maternal asthma with infant bronchiolitis on time to SUID. SUID and bronchiolitis both occurred more frequently in winter. An increase in bronchiolitis clinical visits occurred within a few days prior to apnea visits. We found a temporal relationship between infant bronchiolitis and apnea. In contrast, no peak in SUID cases was seen during peaks of bronchiolitis. Among those without any bronchiolitis visits, maternal smoking was associated with an increased risk of SUID: Hazard Ratio (HR) of 2.38 (95% CI: 2.11, 2.67, p-value <0.001). Maternal asthma was associated with an increased risk of SUID among infants with at least one bronchiolitis visit: HR of 2.40 (95% CI: 1.04, 5.54, p-value = 0.04). Consistent trends between bronchiolitis, apnea, and SUID were not established due to small numbers of SUID cases. However, interaction analysis revealed potential differential associations of bronchiolitis and SUID by maternal smoking, maternal asthma status. PMID- 27404387 TI - Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia. AB - Bovine tuberculosis (bTB) infection is generally correlated with individual cattle's age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife-including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia's highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in pastoral areas should consider herd size and movement as important risk factors. PMID- 27404389 TI - A Bending Test for Determining the Atterberg Plastic Limit in Soils. AB - The thread rolling test is the most commonly used method to determine the plastic limit (PL) in soils. It has been widely criticized, because a considerable subjective judgment from the operator that carries out the test is involved during its performance, which may affect the final result significantly. Different alternative methods have been put forward, but they cannot compete with the standard rolling test in speed, simplicity and cost. In an earlier study by the authors, a simple method with a simple device to determine the PL was presented (the "thread bending test" or simply "bending test"); this method allowed the PL to be obtained with minimal operator interference. In the present paper a version of the original bending test is shown. The experimental basis is the same as the original bending test: soil threads which are 3 mm in diameter and 52 mm long are bent until they start to crack, so that both the bending produced and its related moisture content are determined. However, this new version enables the calculation of PL from an equation, so it is not necessary to plot any curve or straight line to obtain this parameter and, in fact, the PL can be achieved with only one experimental point (but two experimental points are recommended). The PL results obtained with this new version are very similar to those obtained through the original bending test and the standard rolling test by a highly experienced operator. Only in particular cases of high plasticity cohesive soils, there is a greater difference in the result. Despite this, the bending test works very well for all types of soil, both cohesive and very low plasticity soils, where the latter are the most difficult to test via the standard thread rolling method. PMID- 27404388 TI - FGF2 Stimulates COUP-TFII Expression via the MEK1/2 Pathway to Inhibit Osteoblast Differentiation in C3H10T1/2 Cells. AB - Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan nuclear receptor that regulates many key biological processes, including organ development and cell fate determination. Although the biological functions of COUP-TFII have been studied extensively, little is known about what regulates its gene expression, especially the role of inducible extracellular factors in triggering it. Here we report that COUP-TFII expression is regulated specifically by fibroblast growth factor 2 (FGF2), which mediates activation of the MEK1/2 pathway in mesenchymal lineage C3H10T1/2 cells. Although FGF2 treatment increased cell proliferation, the induction of COUP-TFII expression was dispensable. Instead, FGF2-primed cells in which COUP-TFII expression was induced showed a low potential for osteoblast differentiation, as evidenced by decreases in alkaline phosphatase activity and osteogenic marker gene expression. Reducing COUP-TFII by U0126 or siRNA against COUP-TFII prevented the anti-osteogenic effect of FGF2, indicating that COUP-TFII plays a key role in the FGF2-mediated determination of osteoblast differentiation capability. This report is the first to suggest that FGF2 is an extracellular inducer of COUP-TFII expression and may suppress the osteogenic potential of mesenchymal cells by inducing COUP-TFII expression prior to the onset of osteogenic differentiation. PMID- 27404390 TI - Suppression of PPARgamma-mediated monoacylglycerol O-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis. AB - Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD(+)/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear how long-term ingestion of ethanol eventually causes lipid accumulation in liver. Here, we demonstrate that chronic ethanol ingestion activates peroxisome proliferator-activated receptor gamma (PPARgamma) and its target gene, monoacylglycerol O-acyltransferase 1 (MGAT1). During ethanol metabolism, a low NAD(+)/NADH ratio repressed NAD-dependent deacetylase sirtuin 1 (SIRT1) activity, concomitantly resulting in increased acetylated PPARgamma with high transcriptional activity. Accordingly, SIRT1 transgenic mice exhibited a low level of acetylated PPARgamma and were protected from hepatic steatosis driven by alcohol or PPARgamma2 overexpression, suggesting that ethanol metabolism causes lipid accumulation through activation of PPARgamma through acetylation. Among the genes induced by PPARgamma upon alcohol consumption, MGAT1 has been shown to be involved in triglyceride synthesis. Thus, we tested the effect of MGAT1 knockdown in mice following ethanol consumption, and found a significant reduction in alcohol-induced hepatic lipid accumulation. These results suggest that MGAT1 may afford a promising approach to the treatment of fatty liver disease. PMID- 27404391 TI - Inhibition of Insulin-Degrading Enzyme Does Not Increase Islet Amyloid Deposition in Vitro. AB - Islet amyloid deposition in human type 2 diabetes results in beta-cell loss. These amyloid deposits contain the unique amyloidogenic peptide human islet amyloid polypeptide (hIAPP), which is also a known substrate of the protease insulin-degrading enzyme (IDE). Whereas IDE inhibition has recently been demonstrated to improve glucose metabolism in mice, inhibiting it has also been shown to increase cell death when synthetic hIAPP is applied exogenously to a beta-cell line. Thus, we wanted to determine whether a similar deleterious effect is observed when hIAPP is endogenously produced and secreted from islets. To address this issue, we cultured hIAPP transgenic mouse islets that have the propensity to form amyloid for 48 and 144 hours in 16.7 mM glucose in the presence and absence of the IDE inhibitor 1. At neither time interval did IDE inhibition increase amyloid formation or beta-cell loss. Thus, the inhibition of IDE may represent an approach to improve glucose metabolism in human type 2 diabetes, without inducing amyloid deposition and its deleterious effects. PMID- 27404392 TI - Analyzing the CDR3 Repertoire with respect to TCR-Beta Chain V-D-J and V-J Rearrangements in Peripheral T Cells using HTS. AB - V-D-J rearrangement of the TCR-beta chain follows the 12/23 rule and the beyond 12/23 restriction. Currently, the proportion and characteristics of TCR-beta chain V-J rearrangement is unclear. We used high-throughput sequencing to compare and analyze TCR-beta chain V-J rearrangement and V-D-J rearrangement in the CDR3 repertoires of T cells from the PBMCs of six volunteers and six BALB/c mice. The results showed that the percentage of V-J rearrangement of the volunteers was approximately 0.7%, whereas that of the mice was 2.2%. The clonality of mice V-J rearrangement was significantly reduced compared with the V-D-J rearrangement, whereas the clonality of human V-J rearrangement was slightly reduced compared with the V-D-J rearrangement. V-J rearrangement in CDR3 involved the significant usage of N, S, F and L, whereas V-D-J rearrangement in CDR3 involved the significant usage of R and G. The levels of V deletion and J deletion in V-J rearrangement were significantly reduced compared with V-D-J rearrangement. TRBD and TRBJ usage in V-J rearrangement differed from that of V-D-J rearrangement, including dominant usage of TRBV and TRBJ and their pairing. Taken together, these results provide new ideas and technology for studies of V-D-J rearrangement and V-J rearrangement in the CDR3 repertoire. PMID- 27404393 TI - Mechanism for insulin-like peptide 5 distinguishing the homologous relaxin family peptide receptor 3 and 4. AB - The relaxin family peptides play a variety of biological functions by activating four G protein-coupled receptors, RXFP1-4. Among them, insulin-like peptide 5 (INSL5) and relaxin-3 share the highest sequence homology, but they have distinct receptor preference: INSL5 can activate RXFP4 only, while relaxin-3 can activate RXFP3, RXFP4, and RXFP1. Previous studies suggest that the A-chain is responsible for their different selectivity for RXFP1. However, the mechanism by which INSL5 distinguishes the homologous RXFP4 and RXFP3 remains unknown. In the present work, we chemically evolved INSL5 in vitro to a strong agonist of both RXFP4 and RXFP3 through replacement of its five B-chain residues with the corresponding residues of relaxin-3. We identified four determinants (B2Glu, B9Leu, B17Tyr, and a rigid B-chain C-terminus) on INSL5 that are responsible for its inactivity at RXFP3. In reverse experiments, we grafted these determinants onto a chimeric R3/I5 peptide, which contains the B-chain of relaxin-3 and the A-chain of INSL5, and retains full activation potency at RXFP3 and RXFP4. All resultant R3/I5 mutants retained high activation potency towards RXFP4, but most displayed significantly decreased or even abolished activation potency towards RXFP3, confirming the role of these four INSL5 determinants in distinguishing RXFP4 from RXFP3. PMID- 27404394 TI - Systems Toxicology Assessment of the Biological Impact of a Candidate Modified Risk Tobacco Product on Human Organotypic Oral Epithelial Cultures. AB - Cigarette smoke (CS) has been reported to increase predisposition to oral cancer and is also recognized as a risk factor for many conditions including periodontal diseases, gingivitis, and other benign mucosal disorders. Smoking cessation remains the most effective approach for minimizing the risk of smoking-related diseases. However, reduction of harmful constituents by heating rather than combusting tobacco, without modifying the amount of nicotine, is a promising new paradigm in harm reduction. In this study, we compared effects of exposure to aerosol derived from a candidate modified risk tobacco product, the tobacco heating system (THS) 2.2, with those of CS generated from the 3R4F reference cigarette. Human organotypic oral epithelial tissue cultures (EpiOral, MatTek Corporation) were exposed for 28 min to 3R4F CS or THS2.2 aerosol, both diluted with air to comparable nicotine concentrations (0.32 or 0.51 mg nicotine/L aerosol/CS for 3R4F and 0.31 or 0.46 mg/L for THS2.2). We also tested one higher concentration (1.09 mg/L) of THS2.2. A systems toxicology approach was employed combining cellular assays (i.e., cytotoxicity and cytochrome P450 activity assays), comprehensive molecular investigations of the buccal epithelial transcriptome (mRNA and miRNA) by means of computational network biology, measurements of secreted proinflammatory markers, and histopathological analysis. We observed that the impact of 3R4F CS was greater than THS2.2 aerosol in terms of cytotoxicity, morphological tissue alterations, and secretion of inflammatory mediators. Analysis of the transcriptomic changes in the exposed oral cultures revealed significant perturbations in various network models such as apoptosis, necroptosis, senescence, xenobiotic metabolism, oxidative stress, and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) signaling. The stress responses following THS2.2 aerosol exposure were markedly decreased, and the exposed cultures recovered more completely compared with those exposed to 3R4F CS. PMID- 27404395 TI - Conference report: the third BIRAX Regenerative Medicine Conference. AB - The third Britain/Israel Research and Academic Exchange Partnership Regenerative Medicine conference was recently held in Oxford (UK). This conference report summarizes highlights from the scientific program. There is a particular emphasis on internationally collaborative projects funded by this initiative, the young researchers' symposium, and a lively panel session focused on the relationships between industry and academia. PMID- 27404396 TI - Changes in dynamic balance control over time in children with and without Developmental Coordination Disorder. AB - The aim of this study was to examine differences in underlying adaptations of dynamic balance in children with and without Developmental Coordination Disorder (DCD) during a Wii Fit game and to measure changes over time and after intervention. Twenty-eight children with DCD and 21 typically developing (TD) children participated in the study. Analyses of force plate variables showed that the TD group initially used a longer path length for the ski slope descent and tended toward more variation in Center of Pressure (CoP) displacement in lateral direction than the children with DCD. In contrast, the TD group showed a trend of fewer reversals per cm in both AP and lateral direction. After the nonintervention period, the TD group improved performance by decreasing the path length, while the DCD group improved by increasing the path length and by decreasing the number of reversals. After intervention, no changes were found in sway characteristics. Individual analyses within the DCD group showed that the path length per run fell more often within the 95% confidence Interval of the faultless runs. In conclusion both TD and DCD children modify the underlying kinetics of dynamic balance control, but in different ways and both lead to better performance. PMID- 27404397 TI - Validation of maternal cardiac output assessed by transthoracic echocardiography against pulmonary artery catheterization in severely ill pregnant women: prospective comparative study and systematic review. AB - OBJECTIVE: Most severe pregnancy complications are characterized by profound hemodynamic disturbances, thus there is a need for validated hemodynamic monitoring systems for pregnant women. Pulmonary artery catheterization (PAC) using thermodilution is the clinical gold standard for the measurement of cardiac output (CO), however this reference method is rarely performed owing to its invasive nature. Transthoracic echocardiography (TTE) allows non-invasive determination of CO. We aimed to validate TTE against PAC for the determination of CO in severely ill pregnant women. METHODS: This study consisted of a meta analysis combining data from a prospective study and a systematic review. The prospective arm was conducted in Pretoria, South Africa, in 2003. Women with severe pregnancy complications requiring invasive monitoring with PAC according to contemporary guidelines were included. TTE was performed within 15 min of PAC and the investigator was blinded to the PAC measurements. Comparative measurements were extracted from similar studies retrieved from a systematic review of the literature and added to a database. Simultaneous CO measurements by TTE and PAC were compared. Agreement between methods was assessed using Bland Altman statistics and intraclass correlation coefficients (ICC). RESULTS: Thirty four comparative measurements were included in the meta-analysis. Mean CO values obtained by PAC and TTE were 7.39 L/min and 7.18 L/min, respectively. The bias was 0.21 L/min with lower and upper limits of agreement of -1.18 L/min and 1.60 L/min, percentage error was 19.1%, and ICC between the two methods was 0.94. CONCLUSIONS: CO measurements by TTE show excellent agreement with those obtained by PAC in pregnant women. Given its non-invasive nature and availability, TTE could be considered as a reference for the validation of other CO techniques in pregnant women. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN OBJETIVO: Las complicaciones del embarazo mas graves se caracterizan por trastornos hemodinamicos serios, debido a los cuales existe la necesidad de sistemas validados de monitorizacion hemodinamica para mujeres embarazadas. Aunque la cateterizacion de la arteria pulmonar (CAP) mediante termodilucion es el patron de referencia clinico para la medicion del gasto cardiaco (GC), este metodo se usa con poca frecuencia debido a su naturaleza invasiva. La ecocardiografia transtoracica (ETT) permite la determinacion no invasiva del GC. El objetivo de este estudio fue validar la ETT frente al CAP para determinar el GC en mujeres embarazadas gravemente enfermas. METODOS: Este estudio consistio en un metaanalisis que combino datos de un estudio prospectivo y una revision sistematica. El estudio prospectivo se llevo a cabo en Pretoria (Sudafrica) en 2003. Se incluyeron mujeres con complicaciones graves en el embarazo que requerian una monitorizacion invasiva mediante CAP segun las directrices de ese momento. Se realizo una ETT en un plazo de 15 minutos de haber realizado el CAP y el investigador no tuvo acceso a las mediciones del CAP. Las mediciones comparativas se extrajeron de estudios similares obtenidos a partir de una revision sistematica de la literatura y se anadieron a una base de datos. Se compararon las mediciones simultaneas del GC mediante ETT y CAP. La concordancia entre metodos se evaluo a traves del metodo estadistico de Bland-Altman y de coeficientes de correlacion intraclase (CCI). RESULTADOS: Se incluyeron treinta y cuatro mediciones comparativas en el metaanalisis. Los valores medios del GC obtenidos mediante CAP y ETT fueron de 7,39 l/min y 7.18 l/min, respectivamente. El sesgo fue de 0,21 l/min, siendo los limites inferior y superior de la concordancia de -1,18 l/min y 1.60 l/min; el error porcentual fue del 19,1%, y el CCI entre ambos metodos fue de 0,94. CONCLUSIONES: Las mediciones del GC en mujeres embarazadas mediante ETT muestran una excelente concordancia con las obtenidas mediante CAP. Dada su naturaleza no invasiva y su disponibilidad, la ETT podria considerarse como referencia para la validacion de otras tecnicas relacionadas con el GC en mujeres embarazadas. : ,?(pulmonary artery catheterization,PAC)(cardiac output,CO),,?(transthoracic echocardiography,TTE)CO?PACTTECO? : meta?2003?PAC?PAC 15 minTTE,PAC?,?TTEPACCO?Bland-Altman(intraclass correlation coefficients,ICC)? : meta34?PACTTECO7.39 L/min7.18 L/min?-1.18 L/min,1.60 L/min0.21 L/min,19.1%,ICC0.94? : TTECOPACCO?,TTECO?. PMID- 27404398 TI - Effects of ischemic preconditioning on short-duration cycling performance. AB - It has been demonstrated that ischemic preconditioning (IPC) improves endurance performance. However, the potential benefits during anaerobic events and the mechanism(s) underlying these benefits remain unclear. Fifteen recreational cyclists were assessed to evaluate the effects of IPC of the upper thighs on anaerobic performance, skeletal muscle activation, and metabolic responses during a 60-s sprint performance. After an incremental test and a familiarization visit, subjects were randomly submitted in visits 3 and 4 to a performance protocol preceded by intermittent bilateral cuff inflation (4 * (5 min of blood flow restriction + 5 min reperfusion)) at either 220 mm Hg (IPC) or 20 mm Hg (control). To increase data reliability, each intervention was replicated, which was also in a random manner. In addition to the mean power output, the pulmonary oxygen uptake, blood lactate kinetics, and quadriceps electromyograms (EMGs) were analyzed during performance and throughout 45 min of passive recovery. After IPC, performance was improved by 2.1% compared with control (95% confidence intervals of 0.8% to 3.3%, P = 0.001), followed by increases in (i) the accumulated oxygen deficit, (ii) the amplitude of blood lactate kinetics, (iii) the total amount of oxygen consumed during recovery, and (iv) the overall EMG amplitude (P < 0.05). In addition, the ratio between EMG and power output was higher during the final third of performance after IPC (P < 0.05). These results suggest an increased skeletal muscle activation and a higher anaerobic contribution as the ultimate responses of IPC on short-term exercise performance. PMID- 27404399 TI - A Retrospective Study on the Effectiveness of Switching to Oral Methadone for Relieving Severe Cancer-Related Neuropathic Pain and Limiting Adjuvant Analgesic Use in Japan. AB - BACKGROUND: Cancer-related neuropathic pain is resistant to treatment with multiple medications and results in reduced patient quality of life. OBJECTIVE: The aim was to find a new curative to treat neuropathic pain without using adjuvant analgesics. DESIGN: This was a retrospective study that used the FACES Pain Scale (FPS) to measure pain intensity and pain relief. SETTING/SUBJECTS: Twenty-eight inpatients who were treated with other strong opioids and who consulted the palliative care team about their pain relief. RESULTS: In 22 (78.6%) out of 28 patients who successfully switched to methadone from other strong opioids, such as oxycodone and fentanyl, within two weeks, the mean FPS score was significantly reduced from 4.43 to 1.86, and methadone switching either reduced the number of prescriptions or stopped them entirely in 12 out of 17 (70.5%) patients who had used adjuvant analgesics before switching to methadone. CONCLUSIONS: These results suggest that opioid switching to oral methadone not only achieves pain relief but also curtails substantial adjuvant analgesic use. PMID- 27404400 TI - Visualization of Ambient Mass Spectrometry with the Use of Schlieren Photography. AB - This manuscript outlines how to visualize mass spectrometry ambient ionization sources using schlieren photography. In order to properly optimize the mass spectrometer, it is necessary to characterize and understand the physical principles of the source. Most commercial ambient ionization sources utilize jets of nitrogen, helium, or atmospheric air to facilitate the ionization of the analyte. As a consequence, schlieren photography can be used to visualize the gas streams by exploiting the differences in refractive index between the streams and ambient air for visualization in real time. The basic setup requires a camera, mirror, flashlight, and razor blade. When properly configured, a real time image of the source is observed by watching its reflection. This allows for insight into the mechanism of action in the source, and pathways to its optimization can be elucidated. Light is shed on an otherwise invisible situation. PMID- 27404401 TI - Electrical characterization of DNA supported on nitrocellulose membranes. AB - Integrated DNA-based nanoscale electronic devices will enable the continued realization of Moore's Law at the level of functional devices and systems. In this work, the electrical characterization of single and complementary base paired DNA has been directly measured and investigated via the use of nitrocellulose membranes. A radio frequency DAKS-3.5 was used to measure the reflection coefficients of different DNA solutions dotted onto nitrocellulose membranes. Each DNA solution was exposed to a radio frequency signal with a power of 10 dBm and with a sweep from 200 MHz up to 13.6 GHz. The conducted measurements show some distinctions between the homomeric and complementary bases due to their different electrical polarization. As revealed from the measurements conducted, with the addition of DNA oligonucleotides, the measured capacitance increased when compared with buffer medium alone. The DNA molecules could be modeled as dielectric material that can hold electrical charges. Furthermore, the complementary paired DNA molecule-based inks solutions had a higher capacitance value compared with single DNA molecules (A, C, G and T) solutions. PMID- 27404403 TI - Optimization of a Scoring System to Predict Microscopic Colitis in a Cohort of Patients With Chronic Diarrhea. AB - GOALS: Our aim was to develop a scoring system to predict risk of microscopic colitis (MC), to identify patients at low risk, potentially avoiding unnecessary biopsies. BACKGROUND: Patients with chronic diarrhea often undergo colonoscopy with biopsy, but few have histologic abnormalities. STUDY: We conducted a retrospective study of patients with chronic diarrhea and a macroscopically normal colonoscopy at our institution over a 9-month period. Multivariable logistic regression assessed the association between predictors and the presence of biopsy-proven MC. RESULTS: The derivation cohort included 617 patients. Median age was 55.1 (39.6 to 68.1) years; 397 (64.3%) were female and 81 (13.1%) had MC. Age >=55 years, duration of diarrhea <=6 months, >=5 bowel movements per day, body mass index <30 kg/m, current smoking, and current use of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitorss and non steroidal anti-inflammatory drugs were independently associated with MC. A score of >=10 points in our scoring system, yielded an area under the ROC curve (AUC) of 0.83 with a sensitivity of 93% and specificity of 49% in predicting which patients have MC. The negative predictive value (NPV) was 97.8% (95.0% to 99.1%).In the validation cohort, the scoring system performed similarly (AUC 0.79, sensitivity 91%, specificity 49%, NPV 97%). By avoiding biopsies in patients at low risk of having MC, costs associated with colon biopsies could be reduced by almost 43%. CONCLUSION: This scoring system including 7 clinical variables was able to identify patients unlikely to have MC, with excellent sensitivity, reasonable specificity, and a high NPV, translating into important potential cost savings. PMID- 27404402 TI - Sex Chromosome-wide Transcriptional Suppression and Compensatory Cis-Regulatory Evolution Mediate Gene Expression in the Drosophila Male Germline. AB - The evolution of heteromorphic sex chromosomes has repeatedly resulted in the evolution of sex chromosome-specific forms of regulation, including sex chromosome dosage compensation in the soma and meiotic sex chromosome inactivation in the germline. In the male germline of Drosophila melanogaster, a novel but poorly understood form of sex chromosome-specific transcriptional regulation occurs that is distinct from canonical sex chromosome dosage compensation or meiotic inactivation. Previous work shows that expression of reporter genes driven by testis-specific promoters is considerably lower approximately 3-fold or more-for transgenes inserted into X chromosome versus autosome locations. Here we characterize this transcriptional suppression of X linked genes in the male germline and its evolutionary consequences. Using transgenes and transpositions, we show that most endogenous X-linked genes, not just testis-specific ones, are transcriptionally suppressed several-fold specifically in the Drosophila male germline. In wild-type testes, this sex chromosome-wide transcriptional suppression is generally undetectable, being effectively compensated by the gene-by-gene evolutionary recruitment of strong promoters on the X chromosome. We identify and experimentally validate a promoter element sequence motif that is enriched upstream of the transcription start sites of hundreds of testis-expressed genes; evolutionarily conserved across species; associated with strong gene expression levels in testes; and overrepresented on the X chromosome. These findings show that the expression of X-linked genes in the Drosophila testes reflects a balance between chromosome-wide epigenetic transcriptional suppression and long-term compensatory adaptation by sex-linked genes. Our results have broad implications for the evolution of gene expression in the Drosophila male germline and for genome evolution. PMID- 27404405 TI - A Retrospective Review of Forensic Odontology Reports Written by the Joint POW/MIA Accounting Command Central Identification Laboratory for Remains Identified from the Korean War. AB - As of August 2014, the Joint POW/MIA Accounting Command has identified the remains of 1980 previously unknown U.S. service members; 280 were from the Korean War. To determine the accuracy and completeness of the available antemortem (AM) dental records, a review of the AM/postmortem (AM/PM) dental record comparisons from 233 Forensic Odontology Reports written in support of remains identified from the Korean War was performed. Seventy-two AM/PM comparisons resulted in exact dental chartings while 161 contained discrepancies which were explainable. Explainable discrepancies include undocumented treatment (103), incorrectly charted third molars as missing (82), differing opinions of specific molars present/missing (20), and erroneous treatment documentation and/or misidentification of teeth present/missing (22, other than molars). Reassessment has revealed varying levels of completeness for our available AM dental records, the need to thoroughly review our computerized comparisons, adjust our comparisons to include molar pattern variations/third molars, and updating our database comparison program. PMID- 27404406 TI - Measuring Children's Suggestibility in Forensic Interviews. AB - According to the scientific literature, childrens' cognitive development is not complete until adolescence. Therefore, the problems inherent in children serving as witnesses are crucial. In preschool-aged children, false memories may be identified because of misinformation and insight bias. Additionally, they are susceptible of suggestions. The aim of this study was to verify the levels of suggestibility in children between three and 5 years of age. Ninety-two children were examined (44 male, 48 female; M = 4.5 years, SD = 9.62). We used the correlation coefficient (Pearson's r) and the averages variance by SPSS statistical program. The results concluded that: younger children are almost always more susceptible to suggestibility. The dimension of immediate recall was negatively correlates with that of total suggestibility (r = -0.357 p < 0.001). Social compliance and source monitoring errors contribute to patterns of suggestibility, because older children shift their answers more often (r = 0.394 p < 0.001). Younger children change their answers more times (r = -0.395 p < 0.001). PMID- 27404407 TI - Drunk Person Screening using Eye Thermal Signatures. AB - Temperature distribution on the eyes of drunk persons is studied by means of thermal infrared images. The sclera and the iris are of the same temperature for the sober person, while for the intoxicated person, the sclera temperature increases. Consequently, only the thermal images from the drunk persons are necessary for intoxication screening. Forty-one participants drank in a controlled alcohol consumption procedure. Their breath alcohol concentration was above the threshold of 0.2 mg/L of exhaled air, which corresponds to about 0.5 mg of alcohol per cubic centimeter of blood. Histogram modification algorithms were employed to prove that for 36 among the 41 intoxicated persons, the sclera becomes hotter. The Student t-test verified with over 99% confidence the drunk discrimination capabilities of the procedure. The forensic science potential contribution of the method is that face infrared imagery is available to the authorities for supporting intoxication in case of criminal actions. PMID- 27404408 TI - A Valuable Case for Recognizing the Relationship between Arrhythmia and the Biology of Migraine with Brainstem Aura. PMID- 27404409 TI - Authors' Response. PMID- 27404411 TI - QuikQuiz. PMID- 27404410 TI - Politics lnvades Sports Medicine. PMID- 27404412 TI - Scanning sports. PMID- 27404413 TI - Seafood and Your Heart. PMID- 27404414 TI - Hyperactivity, Stimulants, and Sports. PMID- 27404418 TI - Coming in sportsmedicine. PMID- 27404417 TI - 1990 Annual Meeting of the American College of Sports Medicine. PMID- 27404419 TI - Wrap-up. PMID- 27404420 TI - Exercise Dollars: Do They Make Sense? PMID- 27404421 TI - Contusions and the Formation of Myositis Ossificans. AB - In brief: Myositis ossificans-a benign process-is characterized by calcification of a hematoma that resulted from a severe contusion or strain or repeated trauma. Diagnosis is based on radiographic evidence of a calcified mass along with a history of recent trauma to the affected area. Management should be directed at minimizing or preventing extension of the original injury. Rest, ice, compression, and elevation (the classic treatment for any soft-tissue injury) is recommended as initial therapy. Gentle, painless range-of-motion exercises may be prescribed to help restore mobility. Padding can be used to protect the affected area from additional trauma. PMID- 27404422 TI - Emergency Evaluation of Chest Pain. AB - In brief: Occasionally the team physician may be called on to examine someone, a spectator for example, who has chest pain. After ensuring that the person's vital signs are stable, the physician must determine whether the cause is potentially catastrophic or relatively minor. The author describes the distinguishing factors. PMID- 27404423 TI - The Effect of Physical Activity and Inactivity on Aerobic Power in Older Men (A Longitudinal Study). AB - In brief To assess the decline in maximal aerobic power (V O2max) with age, two groups of men were studied: Fifteen exercisers were followed from age 45 to 68, and 15 controls were measured while training at age 52 and again at age 70 after being detrained for 18 years. Resting blood pressure of 120/78 was unchanged in the exercisers but rose from 135/85 to 150/90 in the nonexercisers. V O2max measured by open circuitry declined 13% in the exercisers from 44.4 to 38.6 ml min(-1)-kg(-1); in the nonexercisers it declined 41% from 34.2 to 20.3 ml-min( 1). kg(-1). The V Omax loss was primarily due to a combined loss of maximal heart rate and stroke volume. The data suggest that regular aerobic exercise retards the usual loss in aerobic power with age and present important implications for the aging population in relation to social, economic, and health benefits. PMID- 27404424 TI - Anterior Tibial Pain in a Baseball Player. AB - An overt trauma is not always the source of subsequent swelling and pain. This case conference is a lesson in looking for obscure causes. PMID- 27404425 TI - An Unusual Fracture in Arm Wrestling. AB - In brief: Previous reports of arm wrestling fractures have involved the distal third of the humerus. What makes this case unique is that the fracture occurred at the radial neck. The mechanism of injury probably involved extreme pronation where the radial head is locked into the capitellum-an area of potential weakness. Treatment was conservative, consisting of keeping the elbow flexed, 90 degrees in a sling. PMID- 27404426 TI - Magnetic Resonance Imaging of Major Ligamentous Knee Injuries. AB - In brief: Magnetic resonance imaging (MRI) is useful for assessment of capsuloliga-mentous and other periarticular soft-tissue structures of the knee. It is especially valuable for its ability to accurately diagnose tears of the anterior cruciate ligament (ACL). MRI findings that indicate an ACL tear include frank disruption of the ligament, waviness to the anterior margin of the ligament, and areas of heterogeneous increased signal within the ligament on sagittal T2-weighted images. PMID- 27404427 TI - Hyperactive Children: Which Sports Have the Right Stuff? AB - In brief: The number of children diagnosed as hyperactive continues to grow each year. And a question often arises about whether athletic activity is appropriate for these children. Evidence strongly suggests that not only is it appropriate, but that certain sports can improve self-esteem and can make them feel less like oddities among their peers. PMID- 27404428 TI - Can East German Athletes Hold Their Competitive Edge? AB - East Germany has a long-established reputation for producing some of the world's finest athletes. But now that the reunification of Germany is becoming more likely, many people wonder whether the winning tradition will be lost. PMID- 27404429 TI - Feast or Famine: Eating Disorders in Athletes. AB - Losing weight to improve performance is common-even accepted-among sports competitors. When weight loss gets out of hand, though, coaches and others close to the athlete may have to intervene to help stave off a serious eating disorder. PMID- 27404430 TI - Flexibility for the Ankles and Feet. PMID- 27404432 TI - Increase in Electrical Conductivity of MOF to Billion-Fold upon Filling the Nanochannels with Conducting Polymer. AB - Redox-active pyrrole (Py) monomers were intercalated into 1D nanochannels of [Cd(NDC)0.5(PCA)].Gx (H2NDC = 2,6-napthalenedicarboxylic acid, HPCA = 4 pyridinecarboxylic acid, G = guest molecules) (1) - a fluorescent 3D MOF (lambdaem = 385 nm). Subsequent activation of 1?Py upon immersing into iodine (I2) solution resulted in an increment of the bulk electrical conductivity by ~9 orders of magnitude. The unusual increase in conductivity was attributed to the formation of highly oriented and conducting polypyrrole (PPy) chains inside 1D nanochannels and specific host-guest interaction in 1?PPy thereof. The Hall effect measurements suggested 1?PPy to be an n-type semiconductor material with remarkably high-carrier density (eta) of ~1.5 * 10(17) cm(-3) and mobility (MU) of ~8.15 cm(2) V(-1) s(-1). The fluorescence property of 1 was almost retained in 1?PPy with concomitant exciplex-type emission at higher wavelength (lambdaem = 520 nm). The here-presented results on [MOF?Conducting Polymer] systems in general will serve as a prototype experiment toward rational design for the development of highly conductive yet fluorescent MOF-based materials for various optoelectronic applications. PMID- 27404433 TI - One-step Negative Chromatographic Purification of Helicobacter pylori Neutrophil activating Protein Overexpressed in Escherichia coli in Batch Mode. AB - Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor of Helicobacter pylori (H. pylori). It plays a critical role in H. pylori induced gastric inflammation by activating several innate leukocytes including neutrophils, monocytes, and mast cells. The immunogenic and immunomodulatory properties of HP-NAP make it a potential diagnostic and vaccine candidate for H. pylori and a new drug candidate for cancer therapy. In order to obtain substantial quantities of purified HP-NAP used for its clinical applications, an efficient method to purify this protein with high yield and purity needs to be established. In this protocol, we have described a method for one-step negative chromatographic purification of recombinant HP-NAP overexpressed in Escherichia coli (E. coli) by using diethylaminoethyl (DEAE) ion-exchange resins (e.g., Sephadex) in batch mode. Recombinant HP-NAP constitutes nearly 70% of the total protein in E. coli and is almost fully recovered in the soluble fraction upon cell lysis at pH 9.0. Under the optimal condition at pH 8.0, the majority of HP NAP is recovered in the unbound fraction while the endogenous proteins from E. coli are efficiently removed by the resin. This purification method using negative mode batch chromatography with DEAE ion-exchange resins yields functional HP-NAP from E. coli in its native form with high yield and purity. The purified HP-NAP could be further utilized for the prevention, treatment, and prognosis of H. pylori-associated diseases as well as cancer therapy. PMID- 27404434 TI - An invertebrate-specific and immune-responsive microRNA augments oyster haemocyte phagocytosis by targeting CgIkappaB2. AB - Nuclear factor (NF)-kappaB pathway is an evolutionally conserved pathway in activating immune response, in which IkappaBs can repress the activation. In the present study, cgi-miR-2d, an invertebrate-specific microRNA, was proved to regulate CgIkappaB2 expression and haemocyte phagocytosis during bacterial infection in oyster Crassostrea gigas. The expression of cgi-miR-2d was significantly up-regulated after Vibrio splendidus challenge, while CgIkappaB2 transcripts decreased. Significant decreases in both luminescence and CgIkappaB2 3'UTR level was observed after transfection of cgi-miR-2d in CgIkappaB2 3'UTR luciferase reporter assay. CgIkappaB2 mRNA level decreased significantly (0.51 fold of control group, p < 0.05) in gain-of-function assay of cgi-miR-2d in vivo while it increased markedly (1.27-fold, p < 0.05) when cgi-miR-2d was repressed (0.10-fold, p < 0.01). A significant increase of haemocyte phagocytosis rate was observed in cgi-miR-2d overexpression group (p < 0.01), consistent with results in CgIkappaB2 knock-down group (p < 0.01). Moreover, the apoptosis rate of haemocytes was found significantly declined (28.57%, p < 0.01) in gain-of function assay of cgi-miR-2d. Together, those results not only depicted the functional conservation of miR-2d family in anti-apoptosis of oysters but also highlighted its interaction with phagocytosis by modulating NF-kappaB pathway, which might dedicate critically to the well-balance of host immune response. PMID- 27404435 TI - Reversible thermal unfolding of a yfdX protein with chaperone-like activity. AB - yfdX proteins are ubiquitously present in a large number of virulent bacteria. A member of this family of protein in E. coli is known to be up-regulated by the multidrug response regulator. Their abundance in such bacteria suggests some important yet unidentified functional role of this protein. Here, we study the thermal response and stability of yfdX protein STY3178 from Salmonella Typhi using circular dichroism, steady state fluorescence, dynamic light scattering and nuclear magnetic resonance experiments. We observe the protein to be stable up to a temperature of 45 degrees C. It folds back to the native conformation from unfolded state at temperature as high as 80 degrees C. The kinetic measurements of unfolding and refolding show Arrhenius behavior where the refolding involves less activation energy barrier than that of unfolding. We propose a homology model to understand the stability of the protein. Our molecular dynamic simulation studies on this model structure at high temperature show that the structure of this protein is quite stable. Finally, we report a possible functional role of this protein as a chaperone, capable of preventing DTT induced aggregation of insulin. Our studies will have broader implication in understanding the role of yfdX proteins in bacterial function and virulence. PMID- 27404447 TI - Voice identity processing in autism spectrum disorder. AB - People with autism spectrum disorder (ASD) have difficulties in identifying another person by face and voice. This might contribute considerably to the development of social cognition and interaction difficulties. The characteristics of the voice recognition deficit in ASD are unknown. Here, we used a comprehensive behavioral test battery to systematically investigate voice processing in high-functioning ASD (n = 16) and typically developed pair-wise matched controls (n = 16). The ASD group had particular difficulties with discriminating, learning, and recognizing unfamiliar voices, while recognizing famous voices was relatively intact. Tests on acoustic processing abilities showed that the ASD group had a specific deficit in vocal pitch perception that was dissociable from otherwise intact acoustic processing (i.e., musical pitch, musical, and vocal timbre perception). Our results allow a characterization of the voice recognition deficit in ASD: The findings indicate that in high functioning ASD, the difficulty to recognize voices is particularly pronounced for learning novel voices and the recognition of unfamiliar peoples' voices. This pattern might be indicative of difficulties with integrating the acoustic characteristics of the voice into a coherent percept-a function that has been previously associated with voice-selective regions in the posterior superior temporal sulcus/gyrus of the human brain. Autism Res 2017, 10: 155-168. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27404448 TI - Isolation, Structure Elucidation, and (Bio)Synthesis of Haprolid, a Cell-Type Specific Myxobacterial Cytotoxin. AB - Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound. PMID- 27404449 TI - Detection of respiratory allergies caused by environmental chemical allergen via measures of hyper-activation and degranulation of mast cells in lungs of NC/Nga mice. AB - Respiratory allergy triggered by exposure to environmental chemical allergen is a serious problem in many Asian countries and has the potential to cause severe health problems. Here, we aimed to elucidate the pathogenic mechanisms of this disease and develop an in vivo detection method for respiratory allergy induced by environmental chemical allergen. Both BALB/c and NC/Nga mice were sensitized topically for 3 weeks and were then subjected to inhalation challenge with pulverized trimellitic anhydride into particles measuring 2-MUm in diameter. On the day after the final challenge, all mice were sacrificed, and IgE levels, immunocyte counts, and cytokine levels in the serum, hilar lymph nodes, and bronchoalveolar lavage fluid were measured. We also monitored the expression of genes encoding pro-inflammatory cytokines in the lung. We found that all endpoints were significantly increased in mice of both strains subjected to trimellitic anhydride inhalation as compared with the respective control groups. However, worsening of respiratory status was noted only in NC/Nga mice. Interestingly, type 2 helper T-cell reactions were significantly increased in BALB/c mice compared with that in NC/Nga mice. In contrast, the number of mast cells, levels of mast cell-related cytokine/chemokines, and production of histamine in NC/Nga mice were significantly higher than those in BALB/c mice. Thus, environmental chemical allergen induced respiratory allergy in NC/Nga mice in terms of functional and inflammatory symptoms. Furthermore, mast cells may be involved in the aggravation of airway allergic symptoms induced by environmental chemical allergens. PMID- 27404450 TI - Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of beta-methyl-amino-L-alanine (BMAA). AB - The non-protein amino acid beta-methylamino-L-alanine (BMAA) is a neurotoxin present in microalgae and shown to accumulate in the food web. BMAA has been linked to the complex neurodegenerative disorder of Guam and to increased incidents sporadic ALS. Two main neurotoxic routes are suggested; an excitotoxic by acting as an agonist towards glutamate receptors and a metabolic by misincorporating into cellular proteins. We have used zebrafish, an increasingly used model for neurodegenerative diseases, to further identify signaling components involved in BMAA-induced toxicity. Zebrafish embryos were exposed to sub-lethal dosages of BMAA and a label-free proteomics analysis was conducted on larvae 4 days post fertilization. The exposed larvae showed no developmental abnormalities, but a reduced heart rate and increased expression of GSK3 isoforms. Search towards a reviewed database containing 2968 entries identified 480 proteins. Only 17 of these were regulated 2-fold or more in the exposed larvae. Seven of these proteins could be associated to glutamate receptor signaling and recycling. The remaining nine have all been linked to disturbance in protein homeostasis, reactive oxygen species (ROS) development or neuronal cell death. We also found that BMAA influenced the endocannabinoid system by up regulation of fatty acid amide hydrolase (FAAH) and that FAAH inhibitor URB597 reduced the BMAA effect on heart rate and GSK3 expression. PMID- 27404451 TI - Intertester reliability of shoulder complaints diagnoses in primary health care. AB - OBJECTIVE: Shoulder complaints are frequently encountered in general practice, but precise diagnosing is challenging. This study investigated agreement of shoulder complaints diagnoses between clinicians in a primary health care setting. DESIGN: Cross-sectional study. SETTING: Four primary health care clinicians used patients' history and functional examination of the shoulder by selective tissue tension techniques (STTs), to diagnose shoulder complaints. SUBJECTS: 62 patients, aged 18-75 years. MAIN OUTCOME MEASURE: Reliability of diagnoses was assessed by observed intertester agreement and Cohen's kappa. A total of 372 diagnostic pairs were available for intertester comparisons. RESULTS: Six diagnoses were assigned by all clinicians; supraspinatus-, infraspinatus-, subscapularis-tendinopathies; chronic subacromial bursitis; glenohumeral capsulitis, and acromioclavicular joint lesion. The observed agreement on these diagnoses ranged from 0.84 for glenohumeral capsulitis to 0.97 for acromioclavicular joint lesion. Kappa scores were 0.46 (95% CI 0.33, 0.58) for chronic subacromial bursitis; 0.53 (95% CI 0.34, 0.68), 0.59 (95% CI 0.47, 0.70), and 0.68 (95% CI 0.53, 0.82) for infraspinatus -, supraspinatus -, and subscapularis-tendinopathy, respectively. For glenohumeral capsulitis and acromioclavicular lesion kappa scores were 0.66 (95% CI 0.57, 0.73) and 0.78 (95% CI 0.61, 0.90). Kappa scores were higher for individual diagnoses than for individual tests, except for limitation in passive abduction (0.70, 95% CI 0.62, 0.78) and passive lateral rotation (0.66, 95% CI 0.57, 0.73). CONCLUSIONS: Although experienced clinicians showed substantial intertester agreement, precise diagnoses of shoulder complaints in primary health care remain a challenge. The present results call for further research on refined diagnoses of shoulder complaints. Key points Based on medical history and a systematic functional examination by selective tissue tension techniques (STTs), we investigated the agreement of shoulder complaints diagnoses across four primary health care clinicians and 62 patients. * Agreements on diagnoses were generally better than the agreement on individual tests. * Good kappa scores were obtained for the diagnoses glenohumeral capsulitis, rotator cuff tendinopathy, and acromioclavicular lesion. * Further research is necessary to investigate the diagnostic validity of functional shoulder examination by the STTs method. PMID- 27404452 TI - Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. AB - BACKGROUND: The aim of this study was to reveal the clinicopathological and molecular characteristics of microsatellite instability-high (MSI-H) colorectal cancers (CRCs) showing programmed death ligand-1 (PD-L1) positivity, which are good candidates for anti-PD-1/PD-L1 immunotherapy. METHODS: The PD-L1 expression status of 208 MSI-H CRCs was retrospectively analysed using immunohistochemistry. PD-L1 positivity in tumour cells (PD-L1+(T)) and PD-L1 positivity in immune cells (PD-L1+(I)) were separately evaluated. RESULTS: Programmed death ligand-1 positivity in tumour cells and PD-L1+(I) were observed in 26 (12.5%) and 62 (29.8%) MSI-H CRCs, respectively, and occasionally overlapped (n=12; 5.8%). Programmed death ligand-1 positivity tumours in MSI-H CRCs were significantly associated with older age, female sex, non-mucinous-type poor differentiation, infiltrating growth, tumour budding, advanced stage, CpG island methylator phenotype-high, MLH1 promoter methylation, and BRAF V600E mutations. However, PD L1+(I) MSI-H CRCs were characterised by high-density tumour-infiltrating immune cells, including T cells and macrophages, and intense peritumoural lymphoid reactions. In patients with stage IV MSI-H CRCs who had undergone metastatectomy (n=4), the PD-L1 status of primary tumours was maintained in corresponding distant metastatic lesions. CONCLUSIONS: In MSI-H CRCs, PD-L1+(T) and PD-L1+(I) are linked to a sporadic hypermethylated subtype and an immune cell-rich subtype, respectively. Potential differential therapeutic implications of PD-L1+(T) and PD L1+(I) in CRCs should be further investigated. PMID- 27404453 TI - Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma. AB - BACKGROUND: Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250 mg m(-2) every 2 weeks, respectively; PAXG regimen). METHODS: Nab-paclitaxel doses were escalated from 100 (level one) to 125 (level two) and 150 mg m(-2) (level three) every 2 weeks in cohorts of 3-6 patients with pathologically confirmed unresectable or borderline resectable pancreatic adenocarcinoma. RESULTS: Between Dec 2012 and Apr 2014, 24 patients were enroled (3 at level one, 5 at level two, 16 at level three) and received 117 cycles of PAXG. No dose-limiting toxicity occurred and level three was the RP2D. At this dose, nab-paclitaxel dose-intensity was 91%. Worse per patient grade 3/4 toxicity were neutropenia 25/31%; fatigue 19%; anaemia and hand-foot syndrome 12%, nausea 6%, and febrile neutropenia 6%. A partial response (PR) was observed in 16 (67%) and stable disease (SD) in 8 patients (33%). Among 21 patients with a baseline positive positron emission tomography (PET) scan, a complete metabolic response was observed in 9 (43%), PR in 10 (48%), SD in 2. CA19-9 decreased by ?49% in all the 19 patients with elevated basal value. Six patients were resected after chemotherapy. Progression free survival at 6 months (PFS-6) was 96%. CONCLUSIONS: The RP2D of nab paclitaxel in the PAXG regimen was 150 mg m(-2) every 2 weeks. The preliminary results are promising and warrant further exploration. PMID- 27404454 TI - Tissue factor-bearing microparticles and CA19.9: two players in pancreatic cancer associated thrombosis? AB - BACKGROUND: Cancer-related venous thromboembolism (VTE) heralds a poor prognosis, especially in pancreatic adenocarcinoma (PAC). Tissue factor (TF) is implicated as one of the main culprits in PAC-associated VTE and disease progression. METHODS: In a prospective cohort study of 79 PAC patients, we measured plasma CA19-9 and microparticle-associated TF activity (MP-TF activity). In addition, we enumerated TF(+)MPs and MUC1(+)MPs in plasma (n=55), and studied the expression of TF, MUC1, CD31 and CD68 in tumour tissue (n=44). RESULTS: Plasma MP-TF activity was markedly elevated in PAC patients with VTE compared with those without (median: 1925 vs 113 fM Xa min(-1); P<0.001) and correlated with the extent of thromboembolic events, metastatic disease and short survival. Similar results were found for CA19-9. Patients with massively progressing thrombosis and cerebral embolisms despite anticoagulant therapy (n=3) had the highest MP-TF activities (12 118-40 188 fM Xa min(-1)) and CA19-9 (40 730-197 000 kU l(-1)). All tumours expressed MUC1 and TF. MP-TF activity did not correlate with intensity of TF expression in adenocarcinoma cells, but corresponded with numbers of TF(+) macrophages in the surrounding stroma. CONCLUSIONS: Circulating TF(+)MPs and mucins may concertedly aggravate coagulopathy in PAC. Understanding of underlying mechanisms may result in new treatment strategies for VTE prevention and improvement of survival. PMID- 27404455 TI - Non-canonical NF-kappaB pathway activation predicts outcome in borderline oestrogen receptor positive breast carcinoma. AB - BACKGROUND: NF-kappaB signalling appears deregulated in breast tumours. The purpose of this study was to determine whether the non-canonical NF-kappaB pathway, is activated in oestrogen receptor positive (ER+) breast cancer, to identify any correlation between its activity and the clinico-pathological phenotype and to explore whether NF-kappaB2 and RelB subunits and/or any of their target genes might be used as a predictive marker. METHODS: Two independent cohorts of ER+ early breast cancer patients treated with adjuvant endocrine therapy were included in the study. Activation of RelB and NF-kappaB2 subunits was determined in a training set of 121 patients by measuring DNA-binding activities in nuclear extracts from fresh frozen specimens by an ELISA-based assay. Samples of 15 ER- breast cancer patients were also included in the study. In a large validation cohort of 207 patients, nuclear immunostaining of RelB and NF-kappaB2 on formalin-fixed paraffin-embedded specimens was performed. Statistical correlation within clinico-pathological factors, disease-free survival (DFS) and overall survival (OS) was evaluated. Publicly available gene expression and survival data have been interrogated aimed to identify target genes. RESULTS: Activation of NF-kappaB2 and RelB was found in 53.7 and 49.2% of the 121 ER+ tumours analysed, with similar levels to ER- breast tumours analysed in parallel for comparisons. In the validation cohort, we obtained a similar proportion of cases with activation of NF-kappaB2 and RelB (59.9 and 32.4%), with a 39.6% of co-activation. Multiplexing immunofluorescence in breast cancer tissue confirmed an inverse spatial distribution of ER with NF-kappaB2 and RelB nuclear expression in tumour cells. Interestingly, NF-kappaB2 and RelB mRNA expression was inversely correlated with ER gene (ESR1) levels (P<0.001, both) and its activation was significantly associated with worse DFS (P=0.005 and P=0.035, respectively) in ER+ breast cancer. Moreover, the co-activation of both subunits showed a stronger association with early relapse (P=0.002) and OS (P=0.001). Finally, higher expression of the non-canonical NF-kappaB target gene myoglobin was associated with a poor outcome in ER+ breast cancer (DFS, P<0.05). CONCLUSIONS: The non-canonical NF-kappaB pathway activation is inversely associated with oestrogen receptor expression in ER+ breast cancer and predicts poor survival in this subgroup. The myoglobin gene expression has been identified as a possible surrogate marker of the non-canonical NF-kappaB pathway activation in these tumours. PMID- 27404457 TI - Bone turnover markers in women with early stage breast cancer who developed bone metastases. A prospective study with multivariate logistic regression analysis of accuracy. AB - BACKGROUND: The skeleton is the most common site of metastasis for breast cancer and the periodic measurement of circulating bone turnover markers (BTMs) can be useful. The aim of this study was to prospectively evaluate the diagnostic accuracy of a panel of BTMs in the early detection of bone metastases (BMs). METHODS: We reviewed the medical records of 297 postmenopausal women with early stage luminal-type invasive ductal carcinoma (IDC). Twenty-six patients who developed isolated BMs during follow-up and 24 randomly selected controls were studied. The two groups were matched according to age, final disease staging, and follow-up. All patients underwent periodic measurement of total and bone-specific (BSAP) alkaline phosphatase, CTX, ICTP, osteocalcin, NTX, PINP, and TRACP5b. RESULTS: Only BSAP, CTX, PINP, and TRACP5b were significantly (p<0.05) associated with the group, and the logistic regression analysis excluded CTX from the model. The AUC (ROC curve) for TRACP5b alone, which was the most accurate marker, and for the combination of BSAP+PINP+TRACP5b was 0.784 (95% CI: 0.651-0.916) and 0.889 (95% CI: 0.798-0.981), respectively. CONCLUSION: According to our results, the measurement of these three markers together should be performed in all postmenopausal patients with luminal-type IDC, when an early diagnosis of BMs is required. PMID- 27404456 TI - Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP). AB - BACKGROUND: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). METHODS: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besancon Hospital, France. RESULTS: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log rank P<0.0001). CONCLUSIONS: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future. PMID- 27404459 TI - Genetic diversity, the virulence gene profile and antimicrobial resistance of clinical mastitis-associated Escherichia coli. AB - Escherichia coli is a common cause of bovine mastitis, particularly around parturition and early lactation when the host is immunosuppressed. Isolates (n = 37) recovered from cases of clinical mastitis in Ireland were characterised with respect to genotypic diversity, phylogenetic group, virulence gene profile and antimicrobial susceptibility. The isolates were genotypically diverse, belonging to 19 different sequence types. However, the majority (86%) belonged to phylogenetic groups A or B1, groups commonly associated with commensal E. coli. The isolates encoded few virulence genes with iss (increased serum survival, 41%), lpfA (long polar fimbriae, 19%) and astA (enteroaggregative heat-stable toxin, 14%) among the most common virulence genes detected. The only virulence gene to differ in frequency between the phylogenetic groups was lpfA, found exclusively in B1. Resistance to at least one antimicrobial was detected in 16% of isolates. Three isolates were multidrug-resistant, with one resistant to seven antibiotics. There was no relationship between antimicrobial resistance and phylogenetic group. These results indicate that many cases of clinical E. coli mastitis in Ireland may be caused by opportunistic commensal organisms lacking specific virulence genes. However, the organisms represent a reservoir of antimicrobial resistance determinants with the potential to disseminate determinants to other organisms. PMID- 27404458 TI - Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity. AB - Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (+/-SE) Cr(VI)-reducing ability of post meal samples (20.4+/-2.6MUgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2+/-2.3MUgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post meal samples corresponded to reduction of 13.3+/-1.9 and 25.6+/-2.8MUgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of <=180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. PMID- 27404460 TI - Characterization of newly identified DnaA and DnaB proteins from Acetobacter. AB - Although chromosomal replication is an essential feature of the bacterial life cycle, the replication mechanism and involved molecular players have never been properly characterized in the Acetobacter genera. Thanks to whole-genome sequencing, the unknown replication proteins from Acetobacter pasteurianus and Acetobacter orleanensis, DnaA-like and DnaB-like, could be identified. Despite the low nucleotide or amino acid similarity to the respective orthologs from Escherichia coli, their involvement during replication regulation was corroborated by artificial microRNA. In the Acetobacter genome, a novel replication origin, oriAo, was detected with three 9-nucleotide-long DnaA boxes to which DnaA-like proteins bind actively. Bacterial two-hybrid systems and co immunoprecipitation confirmed the homologous and heterologous interactions between DnaA-like and DnaB-like proteins with their E. coli orthologs. This communication is due to the conserved tryptophan at position 6 for E. coli or 25 for Acetobacter that unables DnaA-like proteins to form oligomeric protein structures after its substitution. Altogether, these results provide novel insights into the genome replication mechanism in Acetobacter. PMID- 27404461 TI - Consideration of Cost of Care in Pediatric Emergency Transfer-An Opportunity for Improvement. AB - BACKGROUND: Pediatric interhospital transfers are an economic burden to the health care, especially when deemed unnecessary. Physicians may be unaware of the cost implications of pediatric emergency transfers. A cost analysis may be relevant to reduce cost. OBJECTIVE: To characterize children transferred from outlying emergency departments (EDs) to pediatric ED (PED) with a specific focus on transfers who were discharged home in 12 hours or less after transfer without intervention in PED and analyze charges associated with them. METHODS: Charts of 352 patients (age, 0-18 years) transferred from 31 outlying EDs to PED during July 2009 to June 2010 were reviewed. Data were collected on the range, unit charge and volume of services provided in PED, length of stay, and final disposition. The average charge per patient transfer is calculated based on unit charge times total service units per 1000 patients per year and divided by 1000. Hospital charges were divided into fixed and variable. RESULTS: Of 352 patients transferred, 108 (30.7%) were admitted to pediatric inpatient service, 42 (11.9%) to intensive care; 36 (10.2%) went to the operating room, and 166 (47.2%) were discharged home. The average hospital charge per transfer was US $4843. Most (89%) of the charges were fixed, and 11% were variable. One hundred one (28.7%) patients were discharged home from PED in 12 hours or less without intervention. The hospital charges for these transfers were US $489,143. CONCLUSIONS: Significant number of transfers was discharged 12 hours or less without any additional intervention in PED. Fixed charges contribute to majority of total charges. Cost saving can be achieved by preventing unnecessary transfer. PMID- 27404462 TI - Emergency Medical Services Provider Pediatric Adverse Event Rate Varies by Call Origin. AB - OBJECTIVE: Emergency medical services providers may be called to a variety of sites to transport pediatric patients, whether it be a scene call for initial evaluation and care, a clinic for transportation of a patient who has been assessed by medical providers, or a hospital where assessment and stabilization have already begun. We hypothesize that there may be a direct relationship between adverse event rates and adverse event severity in transports from less medically stabilizing origins. METHODS: Emergency medical services records of all critical pediatric transports in an urban Oregon county in 2011 were reviewed and abstracted using a standardized tool. From this, UNSEMs (unintended injury, near miss, suboptimal action, error, management complication) were determined, and the potential severity of the issue was assessed. Then, UNSEMs were compared with the origin of transport using logistic regression. RESULTS: Four hundred ninety records were abstracted: 59 hospital transports, 48 clinic transports, and 384 scene transports. Furthermore, UNSEMs were noted in 24 hospital transports (40.7%), 33 clinic transports (68.8%), and 263 scene transports (68.5%). Severe UNSEMs were reported on 0 hospital transports (0.0%), 12 clinic transports (25.0%), and 65 scene transports (16.9%). The odds ratio of UNSEM occurrence from a hospital compared with nonmedical scenes was 0.35 (95% confidence interval, 0.20-0.60), and the odds ratio of a severe UNSEM from a hospital compared with nonmedical scenes was 0.09 (95% confidence interval, 0.01-0.63). CONCLUSIONS: In conclusion, UNSEMs involving the emergency medical services care of children are more likely to occur when transport originates from a clinic or scene compared with a hospital. PMID- 27404463 TI - Need for Lumbar Puncture in Children Younger Than 12 Months Presenting With Simple Febrile Seizure. AB - OBJECTIVES: Recently, conflicting results have been reported regarding the necessity of routine lumbar puncture in children less than 12 months of age with simple febrile seizure. The aims of this study were to evaluate the results of lumbar puncture in children younger than 60 months of age with febrile seizure and to reassess the need for lumbar puncture in children younger than 12 months with simple febrile seizure. METHODS: A retrospective chart review was performed in patients younger than 60 months who presented with febrile seizure and underwent lumbar puncture from January 2005 to January 2015. RESULTS: A total of 1249 patients presenting with febrile seizure were admitted. Of these, 816 met inclusion criteria for presenting with simple febrile seizure. Lumbar puncture was performed in 75 patients (9.2%; age, mean +/- SD, 12.05 +/- 9.13 months; male/female, 31/44), who were reviewed. Sixty-six (88.0%) of 75 patients were younger than 12 months. Five patients (6.7%) showed pleocytosis in cerebrospinal fluid, and 4 of them were younger than 1 year of age. Three patients (4.0%) had bacterial meningitis and were 4, 8, and 12 months. Streptococcus pneumoniae (2 patients) and Klebsiella pneumoniae (1 patient) were isolated in cerebrospinal fluid. Nobody had neurologic signs suggesting bacterial meningitis, and all of them completed scheduled immunizations and were up-to-date. CONCLUSION: Lumbar puncture should be considered in every child younger than 12 months of age with a simple febrile seizure owing to lack of abnormal neurologic sign even if immunization is up-to-date. PMID- 27404464 TI - Children Covered by Medicaid/State Children's Health Insurance Program More Likely to Use Emergency Departments for Food Allergies. AB - BACKGROUND: Food allergies (FAs) occur in 4% to 8% of children in the United States, and emergency department (ED) visits account for up to 20% of their costs. In 2010, the National Institute of Allergy and Infectious Diseases established diagnostic criteria and management practices for FAs, and recognition and treatment of FAs for pediatric ED practitioners has been described. OBJECTIVE: This study identified trends and factors related to ED visits for pediatric FAs in the United States from 2001 to 2010. It was hypothesized that FAs increased and that differences existed in ED utilization based on age, insurance status, and geography. Low concordance with treatment guidelines for FAs was expected. METHODS: Multivariate logistic regression, using National Hospital Ambulatory Medical Care Survey data, estimated factors associated with ED visits and treatment of FAs and nonspecific allergic reactions. Trends and treatment patters used weighted frequencies to account for the complex 4-stage probability survey design. RESULTS: An estimated 239,303 (95% confidence interval [CI], 180,322-298,284) children visited the ED for FAs, demonstrating a significant rate increase during the period (53.08, P < 0.001). Logistic regression showed that the odds of ED visits for FAs were significantly associated with Medicaid/State Children's Health Insurance Program insurance (OR, 1.65 [95% CI, 1.01-2.69], P = 0.04), adolescents (OR, 1.92 [95% CI, 1.10-3.35], P = 0.02), and boys (OR, 1.55 [95% CI, 1.03-2.35], P = 0.04). Treatment with epinephrine for anaphylaxis diagnoses occurred in 57.4% of visits (95% CI, 42.3% 66.8%). CONCLUSIONS: Medicaid/State Children's Health Insurance Program-insured pediatric patients had higher odds of visiting ED for recognized FAs and nonspecific allergic reactions and higher odds of receiving epinephrine than privately insured children. PMID- 27404465 TI - Hydrogen Bonding Slows Down Surface Diffusion of Molecular Glasses. AB - Surface-grating decay has been measured for three organic glasses with extensive hydrogen bonding: sorbitol, maltitol, and maltose. For 1000 nm wavelength gratings, the decay occurs by viscous flow in the entire range of temperature studied, covering the viscosity range 10(5)-10(11) Pa s, whereas under the same conditions, the decay mechanism transitions from viscous flow to surface diffusion for organic glasses of similar molecular sizes but with no or limited hydrogen bonding. These results indicate that extensive hydrogen bonding slows down surface diffusion in organic glasses. This effect arises because molecules can preserve hydrogen bonding even near the surface so that the loss of nearest neighbors does not translate into a proportional decrease of the kinetic barrier for diffusion. This explanation is consistent with a strong correlation between liquid fragility and the surface enhancement of diffusion, both reporting resistance of a liquid to dynamic excitation. Slow surface diffusion is expected to hinder any processes that rely on surface transport, for example, surface crystal growth and formation of stable glasses by vapor deposition. PMID- 27404466 TI - Predicting Sources of Dissolved Organic Nitrogen to an Estuary from an Agro-Urban Coastal Watershed. AB - Dissolved organic nitrogen (DON) is the nitrogen (N)-containing component of dissolved organic matter (DOM) and in aquatic ecosystems is part of the biologically reactive nitrogen pool that can degrade water quality in N-sensitive waters. Unlike inorganic N (nitrate and ammonium) DON is comprised of many different molecules of variable reactivity. Few methods exist to track the sources of DON in watersheds. In this study, DOM excitation-emission matrix (EEM) fluorescence of eight discrete DON sources was measured and modeled with parallel factor analysis (PARAFAC) and the resulting model ("FluorMod") was fit to 516 EEMs measured in surface waters from the main stem of the Neuse River and its tributaries, located in eastern North Carolina. PARAFAC components were positively correlated to DON concentration. Principle components analysis (PCA) was used to confirm separation of the eight sources and model validation was achieved by measurement of source samples not included in the model development with an error of <10%. Application of FluorMod to surface waters of streams within the Neuse River Basin showed that while >70% of DON was attributed to natural sources, nonpoint sources, such as soil and poultry litter leachates and street runoff, accounted for the remaining 30%. This result was consistent with changes in land use from urbanized Raleigh metropolitan area to the largely agricultural Southeastern coastal plain. Overall, the predicted fraction of nonpoint DON sources was consistent with previous reports of increased organic N inputs in this river basin, which are suspected of impacting the water quality of its estuary. PMID- 27404467 TI - An Overview of Asian Rhinoplasty. AB - East Asian rhinoplasty is an expanding topic in the field of rhinoplasty. Although the main principles of various rhinoplasty techniques apply equally to the East Asian nose, East Asian rhinoplasty is unique owing to its different anatomy and ethnicity. In recent years, there have been some noteworthy developments in East Asian rhinoplasty. Traditional techniques using alloplastic implants with endonasal approach are changing due to the advent of new beauty concept, introduction of new techniques, and development of newly improved materials expended polytetrafluoroethylene as an alloplastic material has gained popularity in Asian augmentation rhinoplasty. Soft expended polytetrafluoroethylene sheets as augmentation material provide promise in the future. In this review, we will highlight some of the recent advances of Asian rhinoplasty with emphasis on dorsal augmentation, advances in implant material, and tip surgery using autologous cartilage. PMID- 27404468 TI - Fibro-Lipo-Lymph-Aspiration With a Lymph Vessel Sparing Procedure to Treat Advanced Lymphedema After Multiple Lymphatic-Venous Anastomoses: The Complete Treatment Protocol. AB - BACKGROUND: In lymphedema, excess adipose tissue occurs with progression of the disease because of chronic lymph stasis, impeding lymphatic flow. Recently, liposuction has been used as a less-invasive procedure to remove this excess tissue. Given the existing poor lymph drainage in patients with lymphatic diseases, extra caution should be taken to avoid damaging lymphatic vessels during liposuction. We developed a new technique (Fibro-Lipo-Lymph-Aspiration with a Lymph Vessel Sparing Procedure [FLLA-LVSP]) to improve chronic swelling in patients with advanced lymphedema. The FLLA-LSVP highlights the superficial lymphatic pathways in the treated limb. This visibility allows surgeons to avoid these pathways, while removing the maximum amount of excess tissue. METHOD: One hundred forty-six patients with primary or secondary lymphedema that had already been treated by lymphatic microsurgery, in Genoa, Italy, were included in this retrospective study. All patients had residual fibrotic/adipose tissue, resistant to conservative treatments. Indocyanine green fluorescent dye and Blue Patent Violet dye were injected laterally/medially to the main superficial veins at the wrist/ankle of the limb to be treated. Using a photodynamic camera, the superficial lymphatic network was made visible and sketched onto the skin in indelible ink. After the microlymphography, the excess adipose tissue was carefully aspirated. Preoperative and postoperative excess limb volume was calculated using circumferential measurements and the formula of a frustum. RESULTS: For the upper limb, 0.80 L, on average, and 2.42 L for the lower limb were removed with the FLLA-LVSP. For the upper limb, there was an average presurgery excess volume of 20.19%, which reduced to 2.68% after the FLLA-LVSP (Z score = -6.90, P < 0.001). Similarly, for the lower limb, there was an average presurgery excess limb volume of 21.24% and a reduction to 2.64% postoperatively (Z score = -3.57, P < 0.01). Immediate postoperative microlymphography and Blue Patent Violet test confirmed no lymphatic complications. No episodes of postoperative infection occurred. CONCLUSIONS: The FLLA-LVSP is efficient. An entire leg can be completed within 90 minutes. Recovery time is short, and cosmetic results are immediate. More importantly, the removal of excess tissue is completed without further damage to lymphatic vessels. When used after microsurgery, FLLA-LVSP offers the possibility of removing almost all obstacles to lymphatic flow. PMID- 27404470 TI - Comparison of Neurosensory Assessment Methods in Plastic Surgery. AB - Sensory assessment of the skin is essential to document the function of the sensory fibers of the tested nerves. The Semmes-Weinstein monofilaments, disk criminator, electrodiagnostic testing, and Pressure-Specified Sensory Device (PSSD) have been currently used to assess sensory function of peripheral nerves. None of these methods is optimal because of different drawbacks; however, an increasing number of articles, which recognize the reliability of PSSD, have been published during the last decade. In this review, following a short overview on basic physiology and assessment methods of the skin sensory receptors, we compared the sensory assessment methods and summarized the applications of the PSSD in the field of different clinical areas, mainly peripheral neuropathies, breast, and flap surgery. PMID- 27404471 TI - Plastic Surgery and the Affordable Care Act. PMID- 27404472 TI - Evidence-Based Regulations. PMID- 27404473 TI - Linear Separation of Toe Syndactyly With Preserved Subcutaneous Vascular Network Skin Grafts. AB - BACKGROUND: Conventional surgery of toe syndactyly is accomplished using a zig zag incision and full thickness or split thickness skin grafting. However, this method has an aesthetic problem with a prominent scar on the dorsal side of the foot. The aim of the article was to investigate the efficacy of a cosmetically conscious operation for syndactylies performed using a single technique. METHODS: A retrospective analysis was performed involving 66 patients with 88 syndactylic toes who presented to the department of plastic and reconstructive surgery at 1 of 3 major institutions during a 16-year period (1998-2014). Syndactylies were classified according to the affected interdigital spaces (IDSs). All cases were treated using the same method: linear skin incisions to divide the digits, triangular flaps on the dorsal and plantar sides of the foot, and preserved subcutaneous vascular network skin grafts from the medial inframalleolar region. RESULTS: The most frequent type of toe syndactyly was IDS-2 (union of the second/third toes), which accounted for 59.1% (39/66) of the cases. The rates of familial anomalies were significantly different between bilateral IDS-2 (4/13) and unilateral IDS-2 (0/24) (P < 0.05, Fisher exact test). There were no severe postoperative complications, including scar contracture or keloid formation. All patients obtained sufficiently deep IDSs, and none required repeat surgery. CONCLUSIONS: A straight incision minimizes the scar observed from the visible side, and preserved subcutaneous vascular network skin grafts prevent postoperative contracture of linear scar. PMID- 27404474 TI - Using a Low Fluence Q-Switched 532/1064-nm Nd: YAG Laser for Facial Skin Depigmentation in Asian Patients: Outcome and Complication Profile Analysis. AB - BACKGROUND AND OBJECTIVES: Low fluence Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers are widely applied for facial depigmentation. Nonetheless, few reports analyze the general outcome, complications, of single and combined therapy of 532/1064-nm Nd:YAG lasers in Asian patients with Fitzpatrick type IV skin. STUDY DESIGN/MATERIALS AND METHODS: We retrospectively reviewed all consecutive patients who completed 5 consecutive sessions at 1-month intervals of treatment with 1064-nm (spot size: 5-7 mm, 1.5-2.0 J/cm) or combined with 532-nm (spot size, 2-3 mm; 0.5-1.5 J/cm) Nd:YAG laser (Laseroptek, Korea) from October 2011 to March 2013. The patients, laser surgeon, and 3 blinded reviewers assessed the outcomes and complications. Improvement was graded as follows: 1, 0%-25%; 2, 26%-50%; 3, 51%-75%; 4, 76-90%; and 5, greater than 90%. Postinflammatory hyperpigmentation (PIH) was documented according to the severity (1, slight; 2, moderate; 3, severe; and 4, extreme). Other post-laser side effects were also documented (eg, scaling, dryness, erythema, and pruritus). RESULTS: Four male patients and 37 female patients were included with a mean age of 38.5 years (SD, 10.1 years). There were no significant differences on patients', surgeon's, or blinded reviewers' improvement gradings. (4.11 +/- 0.62 vs 4.30 +/- 0.46, P = 0.54; 3.88 +/- 0.66 vs 3.89 +/- 0.31, P = 0.50; 3.30 +/- 0.69 vs 3.74 +/- 0.38, P = 0.34). Transient minor side effect occurred as follows: erythema in 9 (22%), pruritus in 7 (17%), dryness in 6 (15%), and scaling in 6 (15%). There was no risk difference in these side effects between groups. The PIH scores were slight in 10 patients (4 in single and 6 in combined), severe in 4 (3 in single and 1 in combined), and extreme in 1 (single therapy). The PIH incidence also did not differ (33.3%, 35.3%; P = 0.58). CONCLUSIONS: We reported satisfactory outcomes after low-fluence Q-switched sole 1064-nm or combined 532/1064-nm therapy. The outcome and complication profiles did not differ between the groups. The PIH incidence was not low, but usually transient. The incidence of severe or extreme PIH was rare. PMID- 27404475 TI - Complication Rate Comparing Variable Angle Distal Locking Plate to Fixed Angle Plate Fixation of Distal Radius Fractures. AB - BACKGROUND: Distal radius fractures are common, accounting for approximately 18% of all fractures in adults. Operative management is common, and there are numerous variants of plates used. However, data on safety and complication rates for different plates are limited. OBJECTIVE: To determine whether the rate of complications differed between two distinct types of volar plate design for distal radius fracture fixation, one using predetermined fixed angles for the locking screws or pegs and the other using a variable angle locking design for the locking screws or pegs. Our null hypothesis was that the rate of complications would be the same in each group. MATERIALS AND METHODS: A retrospective chart review was performed on patients with unstable distal radius fractures treated operatively between 2008 and 2011. Patients treated with external fixation or small fragment plates were excluded; all remaining patients underwent internal fixation with 1 of 3 plate designs: Stryker Universal Distal Radius Plate, Acumed Acu-Loc, or Trimed Volar Bearing Plate. RESULTS: A total of 189 patients underwent surgical treatment for an unstable distal radius fracture with a volar plate. Fixed angle plates were used in 60 patients and polyaxial locking plates using a rotatable bearing were used in 148 patients. In the fixed angle plate group, 11 required a second operation on the affected limb for a total of 18 procedures. In 7 of 11 patients, secondary surgery was directly related to complications from the hardware (symptomatic hardware, loose hardware and tendon rupture). All 7 of these patients were in the fixed angle plate group, for a rate of hardware related complications of 12% (7/60). No hardware related complications occurred in patients in the group treated with a polyaxial locking plate (0/129). The complication rate in the fixed angle plate group is significantly different than 0, the rate observed in the polyaxial locking plate group (z score = 3.95, P < 0.001). CONCLUSIONS: Our data suggest that treatment of unstable distal radius fractures with a volar bearing variable angle plate fixation is safe and effective. In our series, there was a significant reduction in the rate of hardware-related complications with the polyaxial locking plate as compared with a fixed angle plate.Therapeutic, Level III, retrospective comparative study. PMID- 27404476 TI - The Clinical Applicationof Preexpanded and Prefabricated Superthin Skin Perforator Flap for Reconstruction of Post-Burn Neck Contracture. PMID- 27404477 TI - Gynecomastia Surgery-Impact on Life Quality: A Prospective Case-Control Study. AB - OBJECTIVE: To evaluate the results of surgical treatment of gynecomastia in the context of quality of life and satisfaction after the surgery. METHODS: Fifty male patients (mean age, 25.1 years [SD = 8 years]) who underwent surgery for gynecomastia and completed both (preoperative and postoperative) stages of the study were included in the analysis. The quality-of-life evaluation instrument was The Short Form-36 Health Survey Questionnaire. Additionally, we used a short questionnaire including 2 questions about patient satisfaction with gynecomastia surgery. RESULTS: The overall change in life satisfaction after gynecomastia surgery was 1 point on Likert scale (sign test, P < 0.0001). Participants after gynecomastia surgery scored significantly higher than before the procedure in all Short Form-36 Health Survey Questionnaire domains as well as in 2 main scales Psychical and Physical Health. The changes were especially visible for the domain social functioning and a scale Psychical Health (P < 0.0001). CONCLUSIONS: Gynecomastia surgery significantly improved men's life quality in all aspects and especially in the social aspect and psychical health. This indicates that adult men with gynecomastia are a specific group of patients, in which surgery may result in life quality improvement even over the average scores. PMID- 27404478 TI - Re: Functional and Therapeutic Indications of Liposuction: Personal Experience and Review of the Literature. PMID- 27404479 TI - Forty years of structural imaging in psychosis: promises and truth. AB - OBJECTIVE: Since the first study published in the Lancet in 1976, structural neuroimaging has been used in psychosis with the promise of imminent clinical utility. The actual impact of structural neuroimaging in psychosis is still unclear. METHOD: We present here a critical review of studies involving structural magnetic resonance imaging techniques in patients with psychosis published between 1976 and 2015 in selected journals of relevance for the field. For each study, we extracted summary descriptive variables. Additionally, we qualitatively described the main structural findings of each article in summary notes and we employed a biomarker rating system based on quality of evidence (scored 1-4) and effect size (scored 1-4). RESULTS: Eighty studies meeting the inclusion criteria were retrieved. The number of studies increased over time, reflecting an increased structural imaging research in psychosis. However, quality of evidence was generally impaired by small samples and unclear biomarker definitions. In particular, there was little attempt of replication of previous findings. The effect sizes ranged from small to modest. No diagnostic or prognostic biomarker for clinical use was identified. CONCLUSIONS: Structural neuroimaging in psychosis research has not yet delivered on the clinical applications that were envisioned. PMID- 27404480 TI - PEO-PPO-PEO Carriers for rAAV-Mediated Transduction of Human Articular Chondrocytes in Vitro and in a Human Osteochondral Defect Model. AB - Gene therapy is an attractive strategy for the durable treatment of human osteoarthritis (OA), a gradual, irreversible joint disease. Gene carriers based on the small human adeno-associated virus (AAV) exhibit major efficacy in modifying damaged human articular cartilage in situ over extended periods of time. Yet, clinical application of recombinant AAV (rAAV) vectors remains complicated by the presence of neutralizing antibodies against viral capsid elements in a majority of patients. The goal of this study was to evaluate the feasibility of delivering rAAV vectors to human OA chondrocytes in vitro and in an experimental model of osteochondral defect via polymeric micelles to protect gene transfer from experimental neutralization. Interaction of rAAV with micelles of linear (poloxamer PF68) or X-shaped (poloxamine T908) poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) copolymers (PEO-PPO-PEO micelles) was characterized by means of isothermal titration calorimetry. Micelle encapsulation allowed an increase in both the stability and bioactivity of rAAV vectors and promoted higher levels of safe transgene (lacZ) expression both in vitro and in experimental osteochondral defects compared with that of free vector treatment without detrimental effects on the biological activity of the cells or their phenotype. Remarkably, protection against antibody neutralization was also afforded when delivering rAAV via PEO-PPO-PEO micelles in all systems evaluated, especially when using T908. Altogether, these findings show the potential of PEO PPO-PEO micelles as effective tools to improve current gene-based treatments for human OA. PMID- 27404481 TI - Identification of Phase Boundaries and Electrical Properties in Ternary Potassium Sodium Niobate-Based Ceramics. AB - A large piezoelectric constant (d33) of ~480 pC/N was attained in new ternary (1 x-y)K0.5Na0.5Nb0.96Sb0.04O3-xBaSnO3-yBi0.5Na0.5ZrO3 ceramics by forming rhombohedral-orthorhombic-tetragonal (R-O-T) phase boundary using the variations of x and y, and such a phase boundary was successfully confirmed by the convergent beam electron diffraction (CBED) patterns. For (1 x)K0.5Na0.5Nb0.96Sb0.04O3-xBaSnO3, the orthorhombic (O) phase is well-maintained for 0 <= x <= 0.015, and both the R and T phases can be introduced to (0.99 y)K0.5Na0.5Nb0.96Sb0.04O3-0.01BaSnO3-yBi0.5Na0.5ZrO3 with y = 0.025-0.04 by simultaneously tailoring their compositions (x and y); then, R-O-T multiphases can be well-established. The CBED patterns strongly support the existence of R-O T multiphases in the ceramics with y = 0.035. When the phase transitions endure from O to R-O-T, their piezoelectric activity endures a leapfrog development from ~165 to ~480 pC/N. In the region of the R-O-T phase boundary, a large d33 of ~480 pC/N was attained in the ceramics with x = 0.01 and y = 0.035. In addition, the ceramics with x = 0.01 and y = 0.04 possess a high strain of ~0.274% due to the multiphases coexistence. According to the variations of dielectric and ferroelectric properties, the enhancement in epsilonr and Pr plays a part in the improved d33 except for the R-O-T phase boundary. We believe that the (K, Na)NbO3 ternary systems can be used to promote piezoelectric activity by forming new phase boundaries. PMID- 27404482 TI - Pluripotent stem cells as a model for embryonic patterning: From signaling dynamics to spatial organization in a dish. AB - In vivo studies have identified the signaling pathways and transcription factors involved in patterning the vertebrate embryo, but much remains unknown about how these are organized in space and time to orchestrate embryogenesis. Recently, embryonic stem cells have been established as a platform for studying spatial pattern formation and differentiation dynamics in the early mammalian embryo. The ease of observing and manipulating stem cell systems promises to fill gaps in our understanding of developmental dynamics and identify aspects that are uniquely human. Developmental Dynamics 245:976-990, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27404483 TI - Finding faces, animals, and vehicles in far peripheral vision. AB - Neuroimaging studies have shown that faces exhibit a central visual field bias, as compared to buildings and scenes. With a saccadic choice task, Crouzet, Kirchner, and Thorpe (2010) demonstrated a speed advantage for the detection of faces with stimuli located 8 degrees from fixation. We used the same paradigm to examine whether the face advantage, relative to other categories (animals and vehicles), extends across the whole visual field (from 10 degrees to 80 degrees eccentricity) or whether it is limited to the central visual field. Pairs of photographs of natural scenes (a target and a distractor) were displayed simultaneously left and right of central fixation for 1s on a panoramic screen. Participants were asked to saccade to a target stimulus (faces, animals, or vehicles). The distractors were images corresponding to the two other categories. Eye movements were recorded with a head-mounted eye tracker. Only the first saccade was measured. Experiment 1 showed that (a) in terms of speed of categorization, faces maintain their advantage over animals and vehicles across the whole visual field, up to 80 degrees and (b) even in crowded conditions (an object embedded in a scene), performance was above chance for the three categories of stimuli at 80 degrees eccentricity. Experiment 2 showed that, when compared to another category with a high degree of within category structural similarity (cars), faces keep their advantage at all eccentricities. These results suggest that the bias for faces is not limited to the central visual field, at least in a categorization task. PMID- 27404484 TI - Chromosome morphometry in opisthorchiid species (Platyhelminthes, Trematoda). AB - Few existing studies have dealt with cytogenetics in trematodes, largely due to the attendant technical difficulty of chromosome preparation. We performed a comparative analysis of chromosomes in five opistorchiid species, including Opisthorchis felineus Rivolta, 1884, Opisthorchis viverrini Poirier, 1886, Clonorchis sinensis Cobbold, 1875, Metorchis xanthosomus Creplin 1846, and Metorchis bilis (Braun, 1790) Odening, 1962. For some of these species, no detailed morphometric description of their karyotypes has yet been published; for the karyotype of Metorchis bilis this is the first-ever description. We found that opisthorchiids, like other trematodes, are characterized by karyotypic conservatism (N=6-7) and karyotype asymmetry, although comparison of chromosome morphometric traits did reveal differences between the karyotypes of the species. Moreover, to address certain a methodological issue in trematode chromosome preparation, we analyzed how the source of chromosomal material (partenitae or mature flukes) and the chromosome preparation techniques used (air-drying and cell suspension methods) affected chromosome spreading and size, concluding that the most reliable comparative method involves comparing relative parameters (relative length, arm ratio, centromeric index) of chromosomes prepared using the same technique. PMID- 27404486 TI - Light- and Solvent-Controlled Self-Assembly Behavior of Spiropyran Polyoxometalate-Alkyl Hybrid Molecules. AB - A molecular photochromic spiropyran-polyoxometalate-alkyl organic-inorganic hybrid has been synthesized and fully characterized. The reversible switching of the hydrophobic spiropyran fragment to the hydrophilic merocyanine one can be easily achieved under light irradiation at different wavelengths. This switch changes the amphiphilic feature of the hybrid, leading to a light-controlled self assembly behavior in solution. It has been shown that the hybrid can reversibly self-assemble into vesicles in polar solvents and irreversibly into reverse vesicles in non-polar solvents. The sizes of the vesicles and the reverse vesicles are both tunable by the polarity of the solvent, with the hydrophobic interactions being the main driving force. PMID- 27404487 TI - Fast-track endovascular aortic repair: Interim report from the prospective LIFE registry. AB - OBJECTIVE: To assess the feasibility, safety, and clinical utility of a fast track endovascular aneurysm repair (EVAR) protocol. BACKGROUND: Despite recent advances in EVAR technology and techniques, considerable opportunity exists to further improve EVAR efficiency and outcomes. METHODS: Eligible patients underwent elective EVAR with the Ovation Prime stent graft. Successful completion of the fast-track protocol required bilateral percutaneous access, avoidance of general anesthesia and intensive care unit admission, and next-day discharge. Patients were followed through 1-month post-treatment. RESULTS: Between October 2014 and September 2015, 129 patients were enrolled in the study. Vascular access, stent graft delivery, and stent graft deployment were successful in all patients. The fast-track EVAR protocol was successfully completed in 114 (88%) patients. Bilateral percutaneous access was achieved in 97% of cases. Comparing patients who completed fast-track requirements to those who failed at least one component, procedure time was 86 vs. 122 min, use of general anesthesia was 0% vs. 20%, need for intensive care unit stay was 0% vs. 13%, hospital stay was 1.1 vs. 2.1 days, and postoperative groin pain severity (0-10 scale) was 1.2 vs. 4.0. No type I or III endoleaks, serious device-related adverse events, AAA ruptures, surgical conversions, or AAA-related secondary procedures were reported. One (0.9%) patient in the fast-track group died from acute respiratory failure. CONCLUSIONS: Initial results from the LIFE study are encouraging and suggest that a fast-track protocol is feasible, safe, and may improve efficiency of healthcare resource allocation in select patients undergoing EVAR. (c) 2016 Wiley Periodicals, Inc. PMID- 27404488 TI - Access to Children's Oncology Group and Pediatric Brain Tumor Consortium phase 1 clinical trials: Racial/ethnic dissimilarities in participation. AB - BACKGROUND: Phase 1 clinical trials introduce new therapies to humans with the goal of establishing their safety. A prior Children's Oncology Group (COG) study analyzed the proportional enrollment of patients by race, ethnicity, sex, and age for all trial phases. The current study evaluated the representation of patients by race, ethnicity, sex, and age in phase 1 clinical trials. METHODS: This study evaluated 1348 children with 128 diagnoses enrolled in COG and Pediatric Brain Tumor Consortium phase 1 clinical trials in the United States from February 28, 2000 to December 29, 2008. Observed and expected proportions were calculated according to an established methodology with a representative population from Surveillance, Epidemiology, and End Results data, which included 27,766 children with the same International Classification of Diseases for Oncology (third edition) diagnostic codes. RESULTS: Underrepresentation in phase 1 trials was seen for lymphohematopoietic (LH) tumors (9.3% observed vs 37% expected) versus solid tumors (90.6% observed vs 63% expected). Although representation was fairly proportional, Hispanics (12.6% observed vs 27% expected), particularly Hispanic females (6% observed vs 18% expected), were significantly underrepresented. The 0 to 4-year age group was underrepresented (11.7% observed vs 36.5% expected). By tumor type, the most significantly underrepresented groups were 0- to 4-year-old children and Hispanics for both solid cancers (11% observed vs 34.4% expected for 0- to 4-year-old children and 12% observed vs 24% expected for Hispanics) and LH cancers (16% observed vs 40% expected for 0- to 4-year-old children and 19.4% observed vs 33% expected for Hispanics). CONCLUSIONS: Although sex and racial/ethnic groups are mostly proportionally represented in phase 1 trials, some specific subgroups such as Hispanic children are underrepresented and may benefit from focused accrual. Cancer 2016;122:3207-14. (c) 2016 American Cancer Society. PMID- 27404489 TI - Depression and Anxiety Change from Adolescence to Adulthood in Individuals with and without Language Impairment. AB - This prospective longitudinal study aims to determine patterns and predictors of change in depression and anxiety from adolescence to adulthood in individuals with language impairment (LI). Individuals with LI originally recruited at age 7 years and a comparison group of age-matched peers (AMPs) were followed from adolescence (16 years) to adulthood (24 years). We determine patterns of change in depression and anxiety using the Child Manifest Anxiety Scale-Revised (CMAS-R) and Short Moods and Feelings Questionnaire (SMFQ). In addition to examining associations with gender, verbal and nonverbal skills, we use a time-varying variable to investigate relationships between depression and anxiety symptoms and transitions in educational/employment circumstances. The results show that anxiety was higher in participants with LI than age matched peers and remained so from adolescence to adulthood. Individuals with LI had higher levels of depression symptoms than did AMPs at 16 years. Levels in those with LI decreased post-compulsory schooling but rose again by 24 years of age. Those who left compulsory school provision (regardless of school type) for more choice-driven college but who were not in full-time employment or study by 24 years of age were more likely to show this depression pathway. Verbal and nonverbal skills were not predictive of this pattern of depression over time. The typical female vulnerability for depression and anxiety was observed for AMPs but not for individuals with LI. These findings have implications for service provision, career/employment advice and support for individuals with a history of LI during different transitions from adolescence to adulthood. PMID- 27404490 TI - Development of recombinant matrix metalloproteinase-3 based sandwich ELISA for sero-diagnosis of canine mammary carcinomas. AB - Matrix metalloproteinase-3 is invariably upregulated in cancerous condition. So we aimed to determine serum level of MMP-3 in canine mammary tumors. The gene was expressed in E. coli system as ~43kDa recombinant protein, which was refolded, purified, and confirmed. Hyperimmune serum was raised against the expressed protein in rabbits and mice to standardize sandwich ELISA. ROC analysis revealed largest area under the curve of 0.998 with sensitivity (100%) and specificity (95%) for a cut-off value of 0.363 with respect to histopathological staining. The finding of the present study indicates that MMP-3 can act as a potential molecular marker for serodiagnosis of canine mammary carcinomas. PMID- 27404491 TI - Aromatization of Benzannulated Perylene-3,9-diones: Unexpected Photophysical Properties and Reactivity. AB - Highly unusual properties of acene-based quinones 1A and 1T are reported. They undergo an unexpected combination of Michael and carbonyl additions of aryllithium leading to new triarylated benzoperylenes 3A and 3T. Uncharacteristically for quinones, 1A and 1T display vibronically split absorption bands and small Stokes shifts. The absorption/emission spectra of the highly emissive 1A are almost indistinguishable from those of the aromatized 3A. Additional benzene rings cause a counterintuitive blue shift of the aromatic derivatives (2T/3T), but an expected red shift was observed for the quinone (1T). This behavior is fully supported by DFT calculations and rationalized by considering the longest conjugation path. PMID- 27404485 TI - p62/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer. AB - p62/SQSTM1 is a multifunctional signaling hub and autophagy adaptor with many binding partners, which allow it to activate mTORC1-dependent nutrient sensing, NF-kappaB-mediated inflammatory responses, and the NRF2-activated antioxidant defense. p62 recognizes polyubiquitin chains via its C-terminal domain and binds to LC3 via its LIR motif, thereby promoting the autophagic degradation of ubiquitinated cargos. p62 accumulates in many human liver diseases, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), where it is a component of Mallory-Denk bodies and intracellular hyaline bodies. Chronic p62 elevation contributes to HCC development by preventing oncogene-induced senescence and death of cancer-initiating cells and enhancing their proliferation. In this review, we discuss p62-mediated signaling pathways and their roles in liver pathophysiology, especially NASH and HCC. PMID- 27404493 TI - CFH Y402H and VEGF Polymorphisms and Anti-VEGF Treatment Response in Exudative Age-Related Macular Degeneration. AB - PURPOSE: The aim of this study was to evaluate the prevalence of single nucleotide polymorphisms (SNPs) in complement factor H (CFH) Y402H and VEGF rs2146323 and rs699947 in exudative age-related macular degeneration (AMD) and their relationship with intravitreal anti-VEGF treatment response. METHODS: A total of 109 exudative AMD patients and 70 controls were included. Patients were classified as 'good responders' and 'nonresponders' based on the changes in best corrected visual acuity, central foveal thickness, lesion size, and the persistence of retinal hemorrhage after three dosages of anti-VEGF. We examined CFH, VEGF rs2146323 and rs699947 SNPs, and plasma interleukin-6 (IL-6) levels in both groups. RESULTS: In total, 42 patients (38.5%) and 11 controls (15.7%) had homozygote wild genotype TT (p = 0.002). The variant C allele frequency was 45% in controls and 31.7% in patients (p = 0.011). A and C allele frequencies for VEGF rs699947 and rs2416323 were similar between the control and patient groups (p = 0.947, p = 0.378). Both SNPs were similar in responders and nonresponders. No significant difference was detected between plasma IL-6 levels of the control and AMD groups (p = 0.594), but the levels were higher in good responders than nonresponders (p < 0.001). CONCLUSION: CFH Y402H SNP might be protective for AMD in the Turkish population. VEGF rs2146323 and rs699947 SNPs have no relationship to exudative AMD formation, and none of these seem to have any effect on anti VEGF response. PMID- 27404494 TI - Immobilization and long-term recovery results in large changes in bone structure and strength but no corresponding alterations of osteocyte lacunar properties. AB - The ability of osteocytes to demineralize the perilacunar matrix, osteocytic osteolysis, and thereby participate directly in bone metabolism, is an aspect of osteocyte biology that has received increasing attention during the last couple of years. The aim of the present work was to investigate whether osteocyte lacunar properties change during immobilization and subsequent recovery. A rat cortical bone model with negligible Haversian remodeling effects was used, with temporary immobilization of one hindlimb induced by botulinum toxin. Several complementary techniques covering multiple length scales enabled correlation of osteocyte lacunar properties to changes observed on the organ and tissue level of femoral bone. Bone structural parameters measured by MUCT and mechanical properties were compared to sub-micrometer resolution SR MUCT data mapping an unprecedented number (1.85 million) of osteocyte lacunae. Immobilization induced a significant reduction in aBMD, bone volume, tissue volume, and load to fracture, as well as the muscle mass of rectus femoris. During the subsequent recovery period, the bone structural and mechanical properties were only partly regained in spite of a long-term (28weeks) study period. No significant changes in osteocyte lacunar volume, density, oblateness, stretch, or orientation were detected upon immobilization or subsequent recovery. In conclusion, the bone architecture and not osteocyte lacunar properties or bone material characteristics dominate the immobilization response as well as the subsequent recovery. PMID- 27404492 TI - Putative Epigenetic Involvement of the Endocannabinoid System in Anxiety- and Depression-Related Behaviors Caused by Nicotine as a Stressor. AB - Like various stressors, the addictive use of nicotine (NC) is associated with emotional symptoms such as anxiety and depression, although the underlying mechanisms have not yet been fully elucidated due to the complicated involvement of target neurotransmitter systems. In the elicitation of these emotional symptoms, the fundamental involvement of epigenetic mechanisms such as histone acetylation has recently been suggested. Furthermore, among the interacting neurotransmitter systems implicated in the effects of NC and stressors, the endocannabinoid (ECB) system is considered to contribute indispensably to anxiety and depression. In the present study, the epigenetic involvement of histone acetylation induced by histone deacetylase (HDAC) inhibitors was investigated in anxiety- and depression-related behavioral alterations caused by NC and/or immobilization stress (IM). Moreover, based on the contributing roles of the ECB system, the interacting influence of ECB ligands on the effects of HDAC inhibitors was evaluated in order to examine epigenetic therapeutic interventions. Anxiety-like (elevated plus-maze test) and depression-like (forced swimming test) behaviors, which were observed in mice treated with repeated (4 days) NC (subcutaneous 0.8 mg/kg) and/or IM (10 min), were blocked by the HDAC inhibitors sodium butyrate (SB) and valproic acid (VA). The cannabinoid type 1 (CB1) agonist ACPA (arachidonylcyclopropylamide; AC) also antagonized these behaviors. Conversely, the CB1 antagonist SR 141716A (SR), which counteracted the effects of AC, attenuated the anxiolytic-like effects of the HDAC inhibitors commonly in the NC and/or IM groups. SR also attenuated the antidepressant-like effects of the HDAC inhibitors, most notably in the IM group. From these results, the combined involvement of histone acetylation and ECB system was shown in anxiety- and depression-related behaviors. In the NC treatment groups, the limited influence of SR against the HDAC inhibitor-induced antidepressant-like effects may reflect the characteristic involvement of histone acetylation within the NC-related neurotransmitter systems other than the ECB system. PMID- 27404495 TI - Gene Expression and DNA Methylation Status of Glutathione S-Transferase Mu1 and Mu5 in Urothelial Carcinoma. AB - Bladder cancer is highly recurrent after therapy, which has an enormous impact on the health and financial condition of the patient. It is worth developing diagnostic tools for bladder cancer. In our previous study, we found that the bladder carcinogen BBN increased urothelial global DNA CpG methylation and decreased GSTM1 protein expression in mice. Here, the correlation of BBN decreased GSTM1 and GSTM gene CpG methylation status was analyzed in mice bladders. BBN treatment decreased the protein and mRNA expression of GSTM1, and the CpG methylation ratio of GSTM1 gene promoter was slightly increased in mice bladders. Unlike mouse GSTM1, the human GSTM1 gene tends to be deleted in bladder cancers. Among 7 human bladder cancer cell lines, GSTM1 gene is really null in 6 cell lines except one, T24 cells. The CpG methylation level of GSTM1 was 9.9% and 5-aza-dC did not significantly increase GSTM1 protein and mRNA expression in T24 cells; however, the GSTM5 gene was CpG hypermethylated (65.4%) and 5-aza-dC also did not affect the methylation ratio and mRNA expression. However, in other cell lines without GSTM1, 5-aza-dC increased GSTM5 expression and decreased its CpG DNA methylation ratio from 84.6% to 61.5% in 5637, and from 97.4% to 75% in J82 cells. In summary, two biomarkers of bladder tumor were provided. One is the GSTM1 gene which is down-regulated in mice bladder carcinogenesis and is usually deleted in human urothelial carcinoma, while the other is the GSTM5 gene, which is inactivated by DNA CpG methylation. PMID- 27404496 TI - Biodiversity and Temporal Distribution of Immature Culicidae in the Atlantic Forest, Rio de Janeiro State, Brazil. AB - To increase the knowledge of biodiversity and identify larval habitats used by immature mosquitoes in the Atlantic Forest, we conducted a study in areas with various stages of preservation within the Guapiacu Ecological Reserve in Cachoeiras de Macacu, Rio de Janeiro state. The Culicidae fauna were sampled during February, April, June, August, October, and December 2012; February, March, April, May, June, August, October, and December 2013; and January and March 2014. Immature mosquitoes were collected with dippers and suction tubes (mouth aspirators). Over the sampling period, 2697 larvae of 56 species were collected, some of which are recognized vectors of human diseases. The larval mosquito community found in artificial habitats, temporary ground water, and phytotelmata differed between sites, except for the mosquito fauna in bromeliads, which were almost 80% similar. Species segregation was more evident between larval habitats than between sites. Culex usquatus was the dominant species and colonized the highest number of larval habitats. The artificial larval habitats found in REGUA were colonized by a great diversity of species and high abundance as well, thus human artifacts left by the public in the area that collect water may promote an increase in mosquito populations. Among the species collected, some are known or suspected vectors of pathogens to humans and/or veterinary relevance, and their medical relevance is discussed. PMID- 27404497 TI - A rat model for determining the postprandial response to foods. AB - BACKGROUND: The use of small animal models for studying postprandial changes in circulating nutrients, hormones and metabolic biomarkers is hampered by the limited quantity of blood that can be withdrawn for analysis. Here, we describe the development of an unrestrained, meal-fed rat model, having a permanent or temporary vascular cannula that permits repeated blood sampling. The applicability and performance of the model were evaluated in a series of experiments on acute glycaemic and insulinaemic responses to carbohydrate-based test meals. RESULTS: A test food containing 0.4 g carbohydrate raised blood glucose by 1.5 mmol L-1 . Postprandial blood glucose levels peaked at 15 min and returned to baseline at 180 min, whereas they remained elevated for longer when the test meal contained 1.25 g carbohydrate. The glycaemic response tended (P = 0.063) to be higher when the meal tolerance test was conducted at the start rather than the end of the dark period, but the insulinaemic response was unaffected. The magnitude of the glycaemic response was less for blood collected from the caudal vein compared to that from the jugular vein. Both cannulation strategies were equally effective in enabling return of red blood cells, thus preserving blood volume. CONCLUSION: This improved small animal model affords new opportunities to screen foods for nutrient bioavailability and explore metabolic mechanisms mediating responses to food consumption. (c) 2016 Society of Chemical Industry. PMID- 27404498 TI - Treatment of aplastic anaemia with lower-dose anti-thymocyte globulin produces similar response rates and survival as per standard dose anti-thymocyte globulin schedules. AB - BACKGROUND: Aplastic anaemia (AA) is a rare acquired bone marrow failure syndrome resulting from the immune-mediated destruction of haemopoietic stem cells. For adults in whom first-line haemopoietic progenitor cell transplantation is not feasible, combination anti-thymocyte globulin (ATGAM) plus cyclosporine A is standard therapy; however, there are minimal data available regarding the optimal ATGAM dosage in terms of efficacy and survival. AIMS: Our institutions have historically used different dosing protocols of ATGAM in the treatment of AA. We aimed to review the outcome of AA patients treated with these protocols and compare them to the published literature. METHODS: We conducted a retrospective study of 31 adults who received first-line ATGAM for AA and compared response rates and survival between cohorts who received standard (40 mg/kg/day D1-4) versus lower-dose (15 mg/kg/day D1-5) ATGAM schedules. RESULTS: There were similar rates of response (64 vs 71%, P = 1.0), relapse (33 vs 33%, P = 1.0), transformation (14 vs 24%, P = 0.66) or infection (43 vs 47%, P = 1.0), respectively, between standard and lower-dose cohorts. At a median follow up of 24 months, there was no statistical difference between standard and lower-dose cohorts in either event-free (42.2 vs 64.7%, P = 0.91) or overall survival (73.1 vs 88.2%, P = 0.75). CONCLUSION: Our experience suggests that lower-dose ATGAM at 15 mg/kg/day D1-5 as treatment of AA produces similar responses and outcomes as per standard-dose ATGAM schedules. Prospective trials comparing ATGAM dose schedules in AA are warranted. PMID- 27404499 TI - Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation. AB - Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA), but controversial in anemia of inflammation (AI). Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA) model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet) prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients. PMID- 27404500 TI - Drug-Mediated Gene Regulation of Vitamin D3 Metabolism in Primary Human Dermal Fibroblasts. AB - Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catabolic reactions (CYP24A1). The cells produced both 25 hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 . The results demonstrate that primary dermal fibroblasts have an active vitamin D3 -metabolizing system. High incidence of low bone mineral density is a concern for HIV-infected patients treated with antiretroviral drugs. Osteomalacia and severe vitamin D deficiency have been reported. We investigated whether drug-mediated gene regulation could be a possible mechanism behind these adverse drug effects. Fibroblasts were treated with different drugs used in HIV therapy, and the 1alpha,25 dihydroxyvitamin D3 levels and relative mRNA levels for crucial enzymes were determined. Efavirenz, stavudine and ritonavir significantly down-regulated the bioactivating CYP2R1 and up-regulated the catabolic CYP24A1. The drugs reduced bioactivating enzyme activities and cellular levels of 1alpha,25-dihydroxyvitamin D3 . The current results indicate that effects on gene expression may lead to disturbed vitamin D metabolism and decreased cellular levels of active vitamin D3 . The data are consistent with the impaired bone health in patients treated with certain antiretroviral drugs. PMID- 27404501 TI - hsa_circRNA_103636: potential novel diagnostic and therapeutic biomarker in Major depressive disorder. AB - AIM: This study aimed to determine whether circular RNA (circRNA) molecules in peripheral blood mononuclear cells (PBMCs) could be used as novel non-invasive biomarkers for major depressive disorder (MDD). MATERIALS & METHODS: Differentially expressed circRNAs were screened using an Arraystar Human CircRNA Array (which includes 13,617 human circRNAs) and qRT-PCR. Thirty MDD patients were randomly selected to retest the circRNA levels after 4-week and 8-week antidepressant regimens. RESULTS: Four differentially expressed circRNAs were identified between MDD patients and controls, and only down-regulated hsa_circRNA_103636 was significantly altered after the 8-week treatment in MDD patients. CONCLUSION: These results suggest that altered expression of hsa_circRNA_103636 in PBMCs is a potential novel biomarker for the diagnosis and treatment of MDD. PMID- 27404503 TI - High Throughput Measurement of Extracellular DNA Release and Quantitative NET Formation in Human Neutrophils In Vitro. AB - Neutrophil granulocytes are the most abundant leukocytes in the human blood. Neutrophils are the first to arrive at the site of infection. Neutrophils developed several antimicrobial mechanisms including phagocytosis, degranulation and formation of neutrophil extracellular traps (NETs). NETs consist of a DNA scaffold decorated with histones and several granule markers including myeloperoxidase (MPO) and human neutrophil elastase (HNE). NET release is an active process involving characteristic morphological changes of neutrophils leading to expulsion of their DNA into the extracellular space. NETs are essential to fight microbes, but uncontrolled release of NETs has been associated with several disorders. To learn more about the clinical relevance and the mechanism of NET formation, there is a need to have reliable tools capable of NET quantitation. Here three methods are presented that can assess NET release from human neutrophils in vitro. The first one is a high throughput assay to measure extracellular DNA release from human neutrophils using a membrane impermeable DNA binding dye. In addition, two other methods are described capable of quantitating NET formation by measuring levels of NET-specific MPO-DNA and HNE-DNA complexes. These microplate-based methods in combination provide great tools to efficiently study the mechanism and regulation of NET formation of human neutrophils. PMID- 27404502 TI - Fecal Transplants: What Is Being Transferred? AB - Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~1011 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~107 per gram of wet stool), archaea (~108 per gram of wet stool), viruses (~108 per gram of wet stool), fungi (~106 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component. PMID- 27404504 TI - Angiotensin II receptor one (AT1) mediates dextrose induced endoplasmic reticulum stress and superoxide production in human coronary artery endothelial cells. AB - BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has been implicated in diabetes-related vascular complications partly through oxidative stress. OBJECTIVE: To determine the role of angiotensin II receptor subtype one (AT1) in dextrose induced endoplasmic reticulum (ER) stress, another cellular stress implicated in vascular disease. METHODS: Human coronary artery endothelial cells with or without AT1 receptor knock down were treated with 27.5mM dextrose for 24h in the presence of various pharmacologic blockers of RAAS and ER stress and superoxide (SO) production were measured. Transfection of cells with AT1 antisense RNA knocked down cellular AT1 by approximately 80%. The ER stress was measured using the placental alkaline phosphatase (ES-TRAP) assay and western blot analysis of glucose regulated protein 78 (GRP78), c-jun-N-terminal kinase 1 (JNK1), phospho-JNK1, eukaryotic translation initiation factor 2alpha (eIF2alpha) and phospho-eIF2alpha measurements. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2 A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. RESULTS: In cells with AT1 knock down, dextrose induced ER stress was significantly blunted and treatment with 27.5mM dextrose resulted in significantly smaller increase in SO production compared to 27.5mM dextrose treated and sham transfected cells. Dextrose induced ER stress was reduced with pharmacologic blockers of AT1 (losartan and candesartan) and mineralocorticoid receptor blocker (spironolactone) but not with angiotensin converting enzyme inhibitors (captopril and lisinopril). The dextrose induced SO generation was inhibited by all pharmacologic blockers of RAAS tested. CONCLUSIONS: The results indicate that dextrose induced ER stress and SO production in endothelial cells are mediated at least partly through AT1 receptor activation. PMID- 27404505 TI - Presenting characteristics and processing times for culturally and linguistically diverse (CALD) patients with chest pain in an emergency department: Time, Ethnicity, and Delay (TED) Study II. AB - BACKGROUND: To date there has been limited published data presenting the characteristics and timeliness of the management in an Emergency Department (ED) for culturally and linguistically diverse (CALD) patients presenting with chest pain. This study aimed to describe the presenting characteristics and processing times for CALD patients with chest pain compared to the Australian-born population, and current guidelines. METHODS: This study was a cross sectional analysis of a cohort of patients who presented with chest pain to the metropolitan hospital between 1 July 2012 and 30 June 2014. RESULTS: Of the total study population (n=6640), 1241 (18.7%) were CALD and 5399 (81.3%) were Australian-born. CALD patients were significantly older than Australian-born patients (mean age 62 vs 56years, p<0.001). There were no differences in the proportion of patients who had central chest pain (74.9% vs 75.7%, p=0.526); ambulance utilisation (41.7% vs 41.1%, p=0.697); and time to initial treatment in ED (21 vs 22min, p=0.375). However, CALD patients spent a significantly longer total time in ED (5.4 vs 4.3h, p<0.001). There was no difference in guideline concordance between the two groups with low rates of 12.5% vs 13%, p=0.556. Nonetheless, CALD patients were 22% (95% CI, 0.65, 0.95, p=0.015) less likely to receive the guideline management for chest pain. CONCLUSIONS: The initial emergency care was equally provided to all patients in the context of a low rate of concordance with three chest pain related standards from the two guidelines. Nonetheless, CALD patients spent a longer time in ED compared to the Australian born group. PMID- 27404506 TI - Transcatheter aortic valve implantation in obese patients: Overcoming technical challenges and maintaining adequate hemodynamic performance using new generation prostheses. AB - BACKGROUND: Second-generation TAVI prostheses may enhance the procedure reducing operative time and complications rate, maintaining adequate valve hemodynamic performance. We present our results with 2 new generation trans-catheter aortic valve (TAVI) prostheses in obese patients. METHODS: A series of 172 patients underwent trans-femoral TAVI with new generation prostheses (Direct Flow Medical, DFM(r), and LOTUS(r)). Two groups were identified according to body mass index (BMI): group NO (125) BMI<30kg/m(2) and group O (47) BMI>=30kg/m(2). RESULTS: Trans-femoral approach was possible in all patients without conversion to conventional surgery/cardiopulmonary bypass. Operative/fluoroscopy time and contrast use were comparable. Vascular and bleeding complications were also equally represented in the 2 groups. Thirty-day mortality was 7.2% in group NO and 6.4% in group O (p=0.9). At discharge, aortic regurgitation was absent/mild in 96% of group NO and in all patients in group O (p=0.3). Mild prosthetic stenosis was reported in 3.8% of the patients in group NO and 2.2% in group O. No moderate/severe prosthetic stenosis was reported. Estimated 1-year survival was 93.1% in group NO and 83.2% in group O (p=0.6). Estimated 1-year freedom from MACCE was 74.7% in group NO and 62.8% in group O (p=0.4). At follow-up echocardiography no significant differences were noticed in the 2 groups. CONCLUSIONS: Second generation TAVI prostheses allow for safe and effective procedures in obese patients. In spite of patient's body habitus, agile prosthesis placement will lead to optimized hemodynamics. Valve and clinical performance are confirmed at follow-up. PMID- 27404507 TI - Semiconducting Polymer Nanobioconjugates for Targeted Photothermal Activation of Neurons. AB - Optogenetics provides powerful means for precise control of neuronal activity; however, the requirement of transgenesis and the incapability to extend the neuron excitation window into the deep-tissue-penetrating near-infrared (NIR) region partially limit its application. We herein report a potential alternative approach to optogenetics using semiconducting polymer nanobioconjugates (SPNsbc) as the photothermal nanomodulator to control the thermosensitive ion channels in neurons. SPNsbc are designed to efficiently absorb the NIR light at 808 nm and have a photothermal conversion efficiency higher than that of gold nanorods. By virtue of the fast heating capability in conjunction with the precise targeting to the thermosensitive ion channel, SPNsbc can specifically and rapidly activate the intracellular Ca(2+) influx of neuronal cells in a reversible and safe manner. Our study provides an organic nanoparticle based strategy that eliminates the need for genetic transfection to remotely regulate cellular machinery. PMID- 27404508 TI - Product Release Pathways in Human and Plasmodium falciparum Phosphoribosyltransferase. AB - Atomistic molecular dynamics (MD) simulations coupled with the metadynamics technique were carried out to delineate the product (PPi.2Mg and IMP) release mechanisms from the active site of both human (Hs) and Plasmodium falciparum (Pf) hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT). An early movement of PPi.2Mg from its binding site has been observed. The swinging motion of the Asp side chain (D134/D145) in the binding pocket facilitates the detachment of IMP, which triggers the opening of flexible loop II, the gateway to the bulk solvent. In PfHGXPRT, PPi.2Mg and IMP are seen to be released via the same path in all of the biased MD simulations. In HsHGPRT too, the product molecules follow similar routes from the active site; however, an alternate but minor escape route for PPi.2Mg has been observed in the human enzyme. Tyr 104 and Phe 186 in HsHGPRT and Tyr 116 and Phe 197 in PfHGXPRT are the key residues that mediate the release of IMP, whereas the motion of PPi.2Mg away from the reaction center is guided by the negatively charged Asp and Glu and a few positively charged residues (Lys and Arg) that line the product release channels. Mutations of a few key residues present in loop II of Trypanosoma cruzi (Tc) HGPRT have been shown to reduce the catalytic efficiency of the enzyme. Herein, in silico mutation of corresponding residues in loop II of HsHGPRT and PfHGXPRT resulted in partial opening of the flexible loop (loop II), thus exposing the active site to bulk water, which offers a rationale for the reduced catalytic activity of these two mutant enzymes. Investigations of the product release from these HsHGPRT and PfHGXPRT mutants delineate the role of these important residues in the enzymatic turnover. PMID- 27404509 TI - Relative Difficulty of Understanding Foreign Accents as a Marker of Proficiency. AB - Foreign-accented speech is generally harder to understand than native-accented speech. This difficulty is reduced for non-native listeners who share their first language with the non-native speaker. It is currently unclear, however, how non native listeners deal with foreign-accented speech produced by speakers of a different language. We show that the process of (second) language acquisition is associated with an increase in the relative difficulty of processing foreign accented speech. Therefore, experiencing greater relative difficulty with foreign accented speech compared with native speech is a marker of language proficiency. These results contribute to our understanding of how phonological categories are acquired during second language learning. PMID- 27404510 TI - Transmission enhancement based on strong interference in metal-semiconductor layered film for energy harvesting. AB - A fundamental strategy to enhance optical transmission through a continuous metallic film based on strong interference dominated by interface phase shift is developed. In a metallic film coated with a thin semiconductor film, both transmission and absorption are simultaneously enhanced as a result of dramatically reduced reflection. For a 50-nm-thick Ag film, experimental transmission enhancement factors of 4.5 and 9.5 are realized by exploiting Ag/Si non-symmetric and Si/Ag/Si symmetric geometries, respectively. These planar layered films for transmission enhancement feature ultrathin thickness, broadband and wide-angle operation, and reduced resistance. Considering one of their potential applications as transparent metal electrodes in solar cells, a calculated 182% enhancement in the total transmission efficiency relative to a single metallic film is expected. This strategy relies on no patterned nanostructures and thereby may power up a wide spectrum of energy-harvesting applications such as thin-film photovoltaics and surface photocatalysis. PMID- 27404511 TI - Synthesis and Evaluation of a New Series of 8-(2-Nitroaryl)Xanthines as Adenosine Receptor Ligands. AB - Preclinical Research A new series of 1,3-dimethylxanthine derivatives bearing 8 (2-nitroaryl) residue was synthesized and evaluated for affinity for recombinant human adenosine receptors subtypes. Nitrate esters of 7-substituted-1,3-dimethyl 8-phenylxanthines were also synthesized and tested. Introducing a nitro substituent at the 2-position of the 8-substituted phenyl ring resulted in generally low affinity for adenosine receptors (ARs), selectivity toward the A2A subtype was enhanced in some of the compounds. 8-(4-Cyclopentyloxy-5-methoxy-2 nitrophenyl)-1,3-dimethylxanthine (9e) proved to be a potent compound among the 2 nitrophenyl substituted xanthines exhibiting a Ki = 1 MUM at human A2A ARs with at least 30 fold selectivity versus human A1 and A2B ARs. Replacement of 8 chloropropoxy phenyl with 8-nitrooxypropoxy phenyl resulted in a negligible change in binding affinity of the 8-substituted xanthines for various AR subtypes. Drug Dev Res 77 : 241-250, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27404512 TI - Activation of human AML14.3D10 eosinophils by nanoparticles: Modulatory activity on apoptosis and cytokine production. AB - Eosinophilic inflammation is frequently observed in response to nanoparticle (NP) exposure in airway rodent models of allergies where the number of eosinophils is increased in lungs. Despite this, it is surprising that the potential cytotoxic effect of NP, as well as their direct role on eosinophils is poorly documented. The present study investigated how different NP can alter the biology of the human eosinophilic cell line AML14.3D10. It was found that among NP forms of CeO2, ZnO, TiO2, and nanosilver of 20 nm (AgNP20) or 70 nm (AgNP70) diameters, only ZnO and AgNP20 induced apoptosis. Caspases-7 and -9 were not activated by the tested NP while caspase-3 was activated by AgNP20 only. However, both ZnO and AgNP20 induced cytoskeletal breakdown as evidenced by the cleavage of lamin B1. Using an ELISArray approach for the simultaneous detection of several analytes (cytokines/chemokines), it was found that only ZnO and AgNP20 increased the production of different analytes including the potent pro-inflammatory CXCL8 (IL 8) chemokine. From the data here, we conclude that toxic effects of some NP could be observed in human eosinophil-like cells and that this could be related, at least partially, by induction of apoptosis and production of cytokines and chemokines involved in inflammation. The results of this study also indicate that distinct NP do not activate similarly human eosinophils, since ZnO and AgNP20 induce apoptosis and cytokine production while others such as TiO2, CeO2, and AgNP70 do not. PMID- 27404513 TI - Derisking Psychiatric Drug Development: The NIMH's Fast Fail Program, A Novel Precompetitive Model. PMID- 27404514 TI - Competition for Cooperation: variability, benefits and heritability of relational wealth in hunter-gatherers. AB - Many defining human characteristics including theory of mind, culture and language relate to our sociality, and facilitate the formation and maintenance of cooperative relationships. Therefore, deciphering the context in which our sociality evolved is invaluable in understanding what makes us unique as a species. Much work has emphasised group-level competition, such as warfare, in moulding human cooperation and sociality. However, competition and cooperation also occur within groups; and inter-individual differences in sociality have reported fitness implications in numerous non-human taxa. Here we investigate whether differential access to cooperation (relational wealth) is likely to lead to variation in fitness at the individual level among BaYaka hunter-gatherers. Using economic gift games we find that relational wealth: a) displays individual level variation; b) provides advantages in buffering food risk, and is positively associated with body mass index (BMI) and female fertility; c) is partially heritable. These results highlight that individual-level processes may have been fundamental in the extension of human cooperation beyond small units of related individuals, and in shaping our sociality. Additionally, the findings offer insight in to trends related to human sociality found from research in other fields such as psychology and epidemiology. PMID- 27404517 TI - Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model. AB - With the rapid development of stem cell-based gene therapies against HIV, there is pressing requirement for an animal model to study the hematopoietic differentiation and immune function of the genetically modified cells. The humanized Bone-marrow/Liver/Thymus (BLT) mouse model allows for full reconstitution of a human immune system in the periphery, which includes T cells, B cells, NK cells and monocytes. The human thymic implant also allows for thymic selection of T cells in autologous thymic tissue. In addition to the study of HIV infection, the model stands as a powerful tool to study differentiation, development and functionality of cells derived from hematopoietic stem cells (HSCs). Here we outline the construction of humanized non-obese diabetic (NOD) severe combined immunodeficient (SCID)-common gamma chain knockout (cgamma(-/-)) Bone-marrow/Liver/Thymus (NSG-BLT) mice with HSCs transduced with CD4 chimeric antigen receptor (CD4CAR) lentivirus vector. We show that the CD4CAR HSCs can successfully differentiate into multiple lineages and have anti-HIV activity. The goal of the study is to demonstrate the use of NSG-BLT mouse model as an in vivo model for engineered immunity against HIV. It is worth noting that, because lentivirus and human tissue is used, experiments and surgeries should be performed in a Class II biosafety cabinet in a Biosafety Level 2 (BSL2) with special precautions (BSL2+) facility. PMID- 27404519 TI - Coming in sportsmedicine. PMID- 27404518 TI - Reading, Writing, and Running. PMID- 27404516 TI - Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial. AB - We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 * 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P interaction = 4.6 * 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P interaction = 3.4 * 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 * 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation. PMID- 27404521 TI - Scanning sports. PMID- 27404522 TI - Brain Injuries in Football. PMID- 27404523 TI - sportsmedicine forum. AB - A Forum For Our Readers Sportsmedicine Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Sportsmedicine Forum, The Physician And Sportsmedicine, 4530 W 77th St, Minneapolis. MN 55435. PMID- 27404526 TI - Swimming Is Not All Bad. PMID- 27404527 TI - Noteworthy. PMID- 27404529 TI - Exercise, Lymphokines, Calories, and Cancer. AB - In brief: Epidemiological studies suggest that exercise reduces the risk of cancer. The leading studies are reviewed here, along with the underlying animal research and the plausible protective mechanisms in humans. The conclusion, based on the literature, is that exercise may help defend against cancer by Preventing obesity, stimulating lymphokines, and/or facilitating other healthful changes in behavior. However, the data are largely preliminary and controversial. Thus, although there is reason to believe that exercise helps prevent cancer, much more research is needed to prove that it does. This article is the first in a series on internal medicine. PMID- 27404530 TI - Cartilaginous Avulsion of the Tibial Eminence and Anterior Cruciate Ligament in a Six-Year-Old Child. AB - In brief: This case report describes an avulsion fracture of the anterior cruciate ligament in a child. Because it was not initially completely reduced, it resulted in limitation of motion. The authors emphasize that even if initial x rays appear normal, further investigation with examination under anesthesia, stress x-ray, arthrography, and arthroscopy should be considered to prevent permanent knee dysfunction. PMID- 27404531 TI - Aerobic Requirements for Moving Handweights Through Various Ranges of Motion While Walking. AB - In brief: This study compared the aerobic metabolic requirements of normal walking (without handweights and with normal arm motions) with requirements of walking while pumping 1-,2-, or 3-lb handweights through Various ranges of motion. Nine male subjects Walked with and without handweights at speeds of 1.12 to 1.79 m. sec(-1). Adding hand-Weighted arm movements significantly increased the oxygen consumption (V O2) of normal walking by 2.1 to 25.5 ml. kg(-1). min( 1). The V O2 for handweighted walking ranged from 17 to 43 ml. kg(-1). min(-1), or 113% to 255% of normal walking requirements at any given speed. These results indicate that walking while moving handweights through large ranges of motion provides a combined upper and lower body aerobic stimulus that is sufficient for endurance training for persons with poor to excellent levels of aerobic fitness. PMID- 27404532 TI - Radionuclide Imaging of Musculoskeletal Injuries in Athletes with Negative Radiographs. AB - In brief: Radionuclide bone scans can be useful in the diagnostic evaluation of musculoskeletal injuries in athletes. Bone scans can detect shinsplints, stress fractures, and muscle injuries before they are detectable on radiographs. Prognosis can be accurately assessed, allowing appropriate treatment to proceed without delay. The authors discuss the use of bone scans and identify musculoskeletal injuries that are associated with specific sports, such as stress fracture of the femur (soccer), tibia (running), scapula (gymnastics), and pars interarticularis (football or lacrosse). PMID- 27404533 TI - Hypermobility and Knee Injuries. AB - In brief: The effect of knee joint hypermobility on knee injury is not fully clear. Inherited flexibility probably plays little role in the causes of most knee injuries. The exception is patellar dislocation, which is strongly associated with hypermobility. Discussions of hypermobility often reflect confusion over the difference between flexibility and laxity. In general, flexibility refers to a joint's range of motion and is a function of muscle and tendon tightness, while laxity refers to joint distraction and shear and is a function of ligament tightness. Research on hypermobility has focused on flexibility; the relationship between injury and joint laxity (ligament stability) has not been studied prospectively. Such research could yield information useful for injury prevention. PMID- 27404534 TI - Characteristics of Anabolic-Androgenic Steroid-Free Competitive Male and Female Bodybuilders. AB - In brief: Anabolic-androgenic steroids are widely used in the community of bodybuilders. We defined a group of steroid-free bodybuilders by analyzing urine for the presence of these steroids, and compared the bodybuilders with both sedentary controls and runners. Male and female competitive bodybuilders had low percentages of body fat. One third of the female bodybuilders reported menstrual abnormalities (more than three missed menses during the past 12 months). Lipid values of bodybuilders were comparable to a group of lean, aerobically trained athletes. Despite their high volume of training, the bodybuilders' oxygen uptake during cycle ergometry was augmented only in proportion to the increase in lean body mass. PMID- 27404535 TI - Eye Protection in Racket Sports: An Update. AB - In brief: A growing number of eye injuries in squash and racquetball in the late 1970s triggered research on eye protectors for these sports. The investigations showed that lensless eye guards were ineffective and that the frames of some lensed eye guards shattered when hit by a ball. Subsequently, Canadian and US organizations set standards for eye guards, requiring that the devices protect the eye from a ball traveling at 90 mph. Seven commercially available eye guards now meet the Canadian or US standard or both. Polycarbonate is the best lens material for eye guards. There is no substitute for approved eye guards; neither experience nor ordinary prescription glasses nor lensless eye guards provide good protection. PMID- 27404536 TI - Mitral Valve Prolapse in Young Patients. AB - In brief: From 1% to 5% of young individuals are found to have, on clinical or echocardiographic examination, a prolapsing mitral valve. The majority of these patients are asymptomatic, and require from the physician an explanation of this defect and reassurance that the condition usually remains mild. Beta-blocking drugs are prescribed for patients with disabling chest pain, dizziness, or palpitation, or if potentially serious rhythm disorders develop. Physicians caring for these young patients must manage each case individually and must remain mindful that the natural course studies come from a perspective of only 25 years. PMID- 27404537 TI - Improving Bicycle Safety for Children. AB - Bicycle-related injuries and deaths are a significant child-health problem that family physicians and pediatricians can help prevent. Children should be required to wear protective helmets and to learn good safety practices. PMID- 27404538 TI - Do Exercise Walkers Need Special Walking Shoes? AB - The emergence of exercise walking as a popular fitness activity has spurred sales of shoes designed and marketed specifically for walking. Consumers may find comfort and stability in these shoes-but certain other shoes may work just as well. PMID- 27404539 TI - Maturation and Strenuous Training in Young Female Athletes. AB - Some research suggests that girls who exercise vigorously may experience disruptions in maturational processes. Robert M. Malina, PhD, evaluates these studies and finds no cause for alarm. PMID- 27404540 TI - Scuba Divers With Disabilities Challenge Medical Protocols and Ethics. AB - Persons with disabilities are scuba diving, as are persons with such conditions as asthma and epilepsy. A recent symposium considered the relevant medical and ethical issues. PMID- 27404541 TI - For Jockeys, Injuries Are Not a Long Shot. AB - No mere lightweights, jockeys are a tough breed of athlete. Their sport subjects them to the risk of serious injury, the stress of extreme competition, and the strain of making weight. PMID- 27404542 TI - Physicians Get In Tune With Performing Artists. AB - Some physicians specialize in treating performing artists, whose medical needs are similar in many ways to those of athletes. PMID- 27404543 TI - Atlantic City: Gambling Is Not Its Only Draw. AB - Long before New Jersey legalized gambling, thousands of summer visitors strolled Atlantic City's famous boardwalk and played in the surf. Today, these and additional pastimes provide fit alternatives to the casinos. PMID- 27404544 TI - Building Bigger Muscles. PMID- 27404546 TI - A Mixed-Methods Analysis of Changing Student Confidence in an Online Shelter Medicine Course. AB - Maddie's Shelter Medicine Program at the University of Florida College of Veterinary Medicine offers comprehensive training in shelter medicine to veterinary students based on a set of core job skills identified by the Association of Shelter Veterinarians. In 2012, this program began teaching online distance education courses to students and practicing veterinarians worldwide who sought additional training in this newly recognized specialty area. Distance learning is a novel educational strategy in veterinary medicine; most instruction at veterinary medical schools is classroom based. No previous studies have shown whether online courses can prepare veterinarians to practice shelter medicine. In this study, we investigated how an online, graduate-level course titled "Shelter Animal Physical Health" changed student self-reported confidence. First, we compared pre-course confidence regarding eight specific shelter medical practice scenarios to post-course confidence through statistical analysis. Quantitative analysis showed a significant (p<.001) increase in self-reported confidence for all eight scenarios. Next, we used open coding to identify themes within reflection papers that students were asked to write during the course and used those findings to corroborate or refute the quantitative results. Qualitative analysis of students' reflection papers identified six themes: confidence, communication, population management, outbreak management, medical care, and application. The results of this study show that distance education can be an effective method of preparing veterinarians and veterinary students to practice shelter medicine. PMID- 27404547 TI - Development and Evaluation of vetPAL, a Student-Led, Peer-Assisted Learning Program. AB - Based on an idea from a final-year student, Bristol Veterinary School introduced vetPAL, a student-led, peer-assisted learning program. The program involved fifth year (final-year) students acting as tutors and leading sessions for fourth-year students (tutees) in clinical skills and revision (review) topics. The initiative aimed to supplement student learning while also providing tutors with opportunities to further develop a range of skills. All tutors received training and the program was evaluated using questionnaires collected from tutees and tutors after each session. Tutees' self-rated confidence increased significantly in clinical skills and for revision topics. Advantages of being taught by students rather than staff included the informal atmosphere, the tutees' willingness to ask questions, and the relatability of the tutors. The small group size and the style of learning in the revision sessions (i.e., group work, discussions, and interactivity) were additional positive aspects identified by both tutees and tutors. Benefits for tutors included developing their communication and teaching skills. The training sessions were considered key in helping tutors feel prepared to lead sessions, although the most difficult aspects were the lack of teaching experience and time management. Following the successful pilot of vetPAL, plans are in place to make the program permanent and sustainable, while incorporating necessary changes based on the evaluation and the student leader's experiences running the program. A vetPAL handbook has been created to facilitate organization of the program for future years. PMID- 27404549 TI - Teaching Professionalism: Using Role-Play Simulations to Generate Professionalism Learning Outcomes. AB - For a constructively aligned curriculum in veterinary professionalism, there is a need for well-designed higher order learning outcomes to support students' professional identity formation. A lack of uniformly accepted definitions of veterinary professionalism necessitates the defining and refining of current concepts of professionalism to inform teaching and assessment. A potential method for achieving such learning outcomes is to generate these from simulated professionalism teaching scenarios. A workshop was designed in which veterinary educators used role play to resolve a professional dilemma. Following discussion of the appropriate management approach, participants were asked to reflect on the learning outcomes that were required to resolve the scenario and that students would achieve by going through the same classroom-based process. Workshop participants identified several professionalism learning outcomes that are not currently defined in the literature: realizing that there is not a single correct answer to a professional dilemma, making a decision despite this uncertainty, communicating differences of opinion, and understanding the effect of differences in professional identity. Although the process described runs counter to traditional curricular design, it may offer a valuable contribution to the discourse surrounding professionalism learning outcomes. Furthermore, it has generated higher level learning outcomes than have been obtained through other methods. PMID- 27404548 TI - Surgical Skills Training with Cryopreserved Rat Stomachs. AB - The objective of this study is to present a high-fidelity bench model of cryopreserved stomachs that can be used while learning surgical skills. Thirty stomachs were harvested from Wistar rats at the end of non-abdominal research studies. The stomachs were washed with cold saline solution and filled with hyaluronic acid solution. The organs were then placed into cryovials and cryopreserved at -30 degrees C for 60 days. The stomachs were thawed to room temperature on the day of the surgical skills practice and two full-thickness incisions were made. Reporting on their experiences, 22 participants (73.33%) felt that the cryopreserved stomach was identical to in vivo rat stomachs, 24 (80.00%) reported that the stomach was easy to handle, and 27 (90%) reported the tissue was non-friable. Moreover, 29 participants (96.6%) finished the suturing without tears and 100% recommended it as a biomaterial for surgical training. The cryopreserved stomach is a practical, reproducible, low-cost, and high-fidelity bench model that allows surgical fellows to learn how to handle a stomach and improve their surgical abilities before performing surgery on patients or laboratory animals. PMID- 27404550 TI - Approaches to Teaching Biometry and Epidemiology at Two Veterinary Schools in Germany. AB - In a thematically broad and highly condensed curriculum like veterinary medicine, it is essential to pay close attention to the didactic and methodical approaches used to deliver that content. The course topics ideally should be selected for their relevance but also for the target audience and their previous knowledge. The overall objective is to improve the long-term availability of what has been learned. For this reason, an evaluation among lecturers of German-speaking veterinary schools was carried out in 2012 to consider which topics in biometry and epidemiology they found relevant to other subject areas. Based on this survey, two veterinary schools (Berlin and Hannover) developed a structured approach for the introductory course in biometry and epidemiology. By means of an appropriate choice of topics and the use of adequate teaching methods, the quality of the lecture course could be significantly increased. Appropriately communicated learning objectives as well as a high rate of student activity resulted in increased student satisfaction. A certain degree of standardization of teaching approaches and material resulted in a comparison between the study sites and reduced variability in the content delivered at different schools. Part of this was confirmed by the high consistency in the multiple-choice examination results between the study sites. The results highlight the extent to which didactic and methodical restructuring of teaching affects the learning success and satisfaction of students. It can be of interest for other courses in veterinary medicine, human medicine, and biology. PMID- 27404552 TI - Exploring the Impact of Tail Polarity on the Phase Behavior of Single Component and Mixed Lipid Monolayers Using a MARTINI Coarse-Grained Force Field. AB - Coarse-grained molecular dynamics simulations have been used to investigate the effect of dipalmitoylphosphatidylcholine (DPPC) tail group polarity on the structural and phase behavior of both single component and binary mixed monolayers using the MARTINI force field. Surface pressure-area isotherms of single component systems indicate that DPPC monolayers become more expanded as a function of increasing tail group polarity, as observed in experimental measurements in the literature. A combination of radial distribution functions and tilt angle measurements indicate that increasing tail group polarity results in the formation of increasingly disordered monolayers. For the mixed monolayer systems, the time dependence of the radial distribution function as well as average cluster size measurements indicate that phase separation takes place between components of different tail group polarity when the monolayers undergo phase transition into disordered configurations. PMID- 27404551 TI - A light-induced shortcut in the planktonic microbial loop. AB - Mixotrophs combine photosynthesis with phagotrophy to cover their demands in energy and essential nutrients. This gives them a competitive advantage under oligotropihc conditions, where nutrients and bacteria concentrations are low. As the advantage for the mixotroph depends on light, the competition between mixo- and heterotrophic bacterivores should be regulated by light. To test this hypothesis, we incubated natural plankton from the ultra-oligotrophic Eastern Mediterranean in a set of mesocosms maintained at 4 light levels spanning a 10 fold light gradient. Picoplankton (heterotrophic bacteria (HB), pico-sized cyanobacteria, and small-sized flagellates) showed the fastest and most marked response to light, with pronounced predator-prey cycles, in the high-light treatments. Albeit cell specific activity of heterotrophic bacteria was constant across the light gradient, bacterial abundances exhibited an inverse relationship with light. This pattern was explained by light-induced top-down control of HB by bacterivorous phototrophic eukaryotes (PE), which was evidenced by a significant inverse relationship between HB net growth rate and PE abundances. Our results show that light mediates the impact of mixotrophic bacterivores. As mixo- and heterotrophs differ in the way they remineralize nutrients, these results have far-reaching implications for how nutrient cycling is affected by light. PMID- 27404553 TI - Bypass of Mutagenic O(6)-Carboxymethylguanine DNA Adducts by Human Y- and B Family Polymerases. AB - The generation of chemical alkylating agents from nitrosation of glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O(6)-carboxymethylguanine (O(6)-CMG) is a product of DNA alkylation derived from nitrosated glycine. Although the tendency of the structurally related adduct O(6)-methylguanine to code for the misincoporation of TTP during DNA replication is well-established, the impact of the presence of the O(6)-CMG adduct in a DNA template on the efficiency and fidelity of translesion DNA synthesis (TLS) by human DNA polymerases (Pols) has hitherto not been described. Herein, we characterize the ability of the four human TLS Pols eta, iota, kappa, and zeta and the replicative Pol delta to bypass O(6)-CMG in a prevalent mutational hot-spot for colon cancer. The results indicate that Pol eta replicates past O(6)-CMG, incorporating dCMP or dAMP, whereas Pol kappa incorporates dCMP only, and Pol iota incorporates primarily dTMP. Additionally, the subsequent extension step was carried out with high efficiency by TLS Pols eta, kappa, and zeta, while Pol iota was unable to extend from a terminal mismatch. These results provide a first basis of O(6)-CMG-promoted base misincorporation by Y- and B-family polymerases potentially leading to mutational signatures associated with colon cancer. PMID- 27404554 TI - Generation of Immature, Mature and Tolerogenic Dendritic Cells with Differing Metabolic Phenotypes. AB - Immune response results from a complex interplay between the antigen non-specific innate immune system and the antigen specific adaptive immune system. The immune system is a constant balance in maintaining tolerance to self-molecules and reacting rapidly to pathogens. Dendritic cells (DCs) are powerful professional antigen presenting cells that link the innate immune system to the adaptive immune system and balance the adaptive response between self and non-self. Depending on the maturation signals, immature dendritic cells can be selectively stimulated to differentiate into immunogenic or tolerogenic DCs. Immunogenic dendritic cells provide proliferation signals to antigen-specific T cells for clonal expansion; while tolerogenic dendritic cells regulate tolerance by antigen specific T-cell deletion or clonal expansion of regulatory T-cells. Due to this unique property, dendritic cells are highly sought after as therapeutic agents for cancer and autoimmune diseases. Dendritic cells can be loaded with specific antigens in vitro and injected into the human body to mount a specific immune response both immunogenic and tolerogenic. This work presents a means to generate in vitro from monocytes, immature monocyte derived dendritic cells (moDCs), tolerogenic and mature moDCs that differ in surface marker expression, function and metabolic phenotypes. PMID- 27404555 TI - Predicting Spontaneous Stone Passage in Prepubertal Children: A Single Institution Cohort. AB - INTRODUCTION: No method currently exists for predicting which young child with a renal or ureteral stone will require surgery as opposed to pass the stone. Our goals were to analyze practice patterns at a major pediatric center and to identify factors that predicted spontaneous stone passage. METHOD: A retrospective review of all prepubertal patients (<= 11 years) presenting to our institution from January 2005 to July 2014 with symptomatic nephrolithiasis was performed. Demographic data and stone details were reviewed, including anatomic location, size, and outcomes. Spontaneous stone passage was determined by parental report and/or stone absence on imaging obtained within 6 months after initial diagnosis. RESULTS: A total of 119 eligible patients were identified, with an average age of 88.7 months (4-143). Forty eight (40.3%) patients spontaneously passed their stone and the remaining 59.7% required endoscopic intervention. Overall, 79.0% had symptomatic presentation (flank pain, hematuria) and 39.5% of patients were obstructing stones. Symptomatic presentation was more common with ureteral (86.5%) than with renal (66.7%) stones, but was not associated with increased passage of stones in general (p-value 0.1765). Of the 48 patients who spontaneously passed stones, 11 (24.4%) were renal stones compared with 37 (50.0%) ureteral stones. The average size of spontaneously passed stones was 3.5 mm (2-8) for renal and 3.4 mm (1-7) for ureteral stones. Based on logistic regression, the single most important predictor of stone passage was stone size (p-value <0.001). The odds of passage were 3.1 times higher for ureteral stones compared with renal stones (p = 0.0070) when not controlling for size. CONCLUSION: In prepubertal patients, ureteral stones with an average size of 3.5 mm or less are more likely to pass spontaneously. Based on this information, watchful waiting is a reasonable option in clinically stable nonseptic patients with renal/ureteral stones of this size. PMID- 27404556 TI - The Cost-Effectiveness of Anemia Treatment for Persons with Chronic Kidney Disease. AB - BACKGROUND: Although major guidelines uniformly recommend iron supplementation and erythropoietin stimulating agents (ESAs) for managing chronic anemia in persons with chronic kidney disease (CKD), there are differences in the recommended hemoglobin (Hb) treatment target and no guidelines consider the costs or cost-effectiveness of treatment. In this study, we explored the most cost effective Hb target for anemia treatment in persons with CKD stages 3-4. METHODS AND FINDINGS: The CKD Health Policy Model was populated with a synthetic cohort of persons over age 30 with prevalent CKD stages 3-4 (i.e., not on dialysis) and anemia created from the 1999-2010 National Health and Nutrition Examination Survey. Incremental cost-effectiveness ratios (ICERs), computed as incremental cost divided by incremental quality adjusted life years (QALYs), were assessed for Hb targets of 10 g/dl to 13 g/dl at 0.5 g/dl increments. Targeting a Hb of 10 g/dl resulted in an ICER of $32,111 compared with no treatment and targeting a Hb of 10.5 g/dl resulted in an ICER of $32,475 compared with a Hb target of 10 g/dl. QALYs increased to 4.63 for a Hb target of 10 g/dl and to 4.75 for a target of 10.5 g/dl or 11 g/dl. Any treatment target above 11 g/dl increased medical costs and decreased QALYs. CONCLUSIONS: In persons over age 30 with CKD stages 3-4, anemia treatment is most cost-effective when targeting a Hb level of 10.5 g/dl. This study provides important information for framing guidelines related to treatment of anemia in persons with CKD. PMID- 27404558 TI - Synthesis and cytotoxicity evaluation of aryl triazolic derivatives and their hydroxymethine homologues against B16 melanoma cell line. AB - In this manuscript we describe synthesis and cytotoxicity evaluation of some triazolic derivatives against B16 melanoma cell line. For this purpose, we transformed a set of aromatic aldehydes into terminal alkynes, using Besthmann Ohira reagent, and we made the corresponding hydroxymethyl homologated alkynes by an acetylene Grignard reagent. These generated two sets of alkynes were then subjected to a copper(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) using a solid-supported catalyst (Amberlyst A-21 CuI), with a third set composed of organic azides. Synthesized triazoles were then tested in vitro against B16 melanoma cell line. Amongst them, compounds a1b1 (R(1) = p-nitrophenyl, R(2) = benzyl), a4b1 (R(1) = naphthyl, R(2) = benzyl) and a4b5 (R(1) = naphthyl, R(2) = (R/S)- dioxolane) showed the best activity against B16 melanoma cells, with IC50 of 5.12, 3.89 and 6.60 MUM respectively. PMID- 27404557 TI - Exploring the readthrough of nonsense mutations by non-acidic Ataluren analogues selected by ligand-based virtual screening. AB - Ataluren, also known as PTC124, is a 5-(fluorophenyl)-1,2,4-oxadiazolyl-benzoic acid suggested to suppress nonsense mutations by readthrough of premature stop codons in the mRNA. Potential interaction of PTC124 with mRNA has been recently studied by molecular dynamics simulations highlighting the importance of H bonding and stacking pi-pi interactions. A series of non-acidic analogues of PTC124 were selected from a large database via a ligand-based virtual screening approach. Eight of them were synthesized and tested for their readthrough activity using the Fluc reporter harboring the UGA premature stop codon. The most active compound was further tested for suppression of the UGA nonsense mutation in the bronchial epithelial IB3.1 cell line carrying the W1282X mutation in the CFTR gene. PMID- 27404559 TI - Vibrational Spectroscopy in Body Fluids Analysis. AB - Vibrational spectroscopy offers a unique opportunity to investigate the composition of unknown substances on a molecular basis. The spectroscopy of molecular vibrations using mid-infrared or Raman techniques has been applied to samples of body fluids. This review presents some applications related to body fluids published in the period 2005-2015. PMID- 27404560 TI - Impact of preoperative defecation pattern on postoperative constipation for patients undergoing cardiac surgery. AB - AIMS AND OBJECTIVES: To analyse the impact of preoperative defecation pattern on postoperative defecation pattern for patients undergoing cardiac surgery. BACKGROUND: Constipation is a neglected problem that occurs frequently after cardiac surgery. DESIGN: Descriptive study. METHOD: The study sample comprised 102 patients who underwent cardiac surgery. A Descriptive Information Form, Rome III Diagnostic Criteria, Constipation Severity Instrument, Postoperative Defecation Pattern Evaluation Form and Bristol Stool Form Scale were used for data collection and analysis. RESULTS: The Constipation Severity Instrument scores of just over one-third (37.2%) of the patients who were constipated prior to surgery were higher compared to those who were not constipated. Following cardiac surgery, 39.2% of patients developed constipation and 80% of these patients were constipated prior to cardiac surgery. The findings indicate a significantly high relationship between preoperative and postoperative defecation pattern (r = 0.71, p < 0.001). CONCLUSION: Preoperative defecation pattern is a determining factor for the development of postoperative constipation for patients undergoing cardiac surgery. RELEVANCE TO CLINICAL PRACTICE: During the preoperative period, clinical nurses may evaluate the patients' defecation patterns using valid and reliable scales and follow the defecation of the patients, especially patients with defecation problems, during the postoperative period. PMID- 27404561 TI - Experimental realization of an entanglement access network and secure multi-party computation. AB - To construct a quantum network with many end users, it is critical to have a cost efficient way to distribute entanglement over different network ends. We demonstrate an entanglement access network, where the expensive resource, the entangled photon source at the telecom wavelength and the core communication channel, is shared by many end users. Using this cost-efficient entanglement access network, we report experimental demonstration of a secure multiparty computation protocol, the privacy-preserving secure sum problem, based on the network quantum cryptography. PMID- 27404562 TI - Design of Assembled Systems Based on Conjugated Polyphenylene Derivatives and Carbon Nanohorns. AB - Promising materials have been designed and fully characterised by an effective interaction between versatile platforms such as carbon nanohorns (CNHs) and conjugated molecules based on thiophene derivatives. Easy and non-aggressive methods have been described for the synthesis and purification of the final systems. Oligothiophenephenylvinylene (OTP) systems with different geometries and electron density are coupled to the CNHs. A wide range of characterization techniques have been used to confirm the effective interaction between the donor (OTP) and the acceptor (CNH) systems. These hybrid materials show potential for integration into solar cell devices. Importantly, surface-enhanced Raman spectroscopy (SERS) effects are observed without the presence of any metal surface in the system. Theoretical calculations have been performed to study the optimised geometries of the noncovalent interaction between the surface and the organic molecule. The calculations allow information on the monoelectronic energies of HOMO-LUMO orbitals and band gap of different donor systems to be extracted. PMID- 27404563 TI - Physical activity in young children and their parents-An Early STOPP Sweden-China comparison study. AB - Understanding about socio-cultural differences in physical activity in children with high and low risk for obesity can help tailor intervention programs in different settings. This study aimed to compare objectively measured physical activity in two-year-olds and their parents, living in Stockholm, Sweden, and Wuhan, China. Data from Early STOPP was used. Children and parents wore an accelerometer in connection with the child's second birthday. Weekly and hourly patterns were examined. Correlation between child and parental physical activity was assessed. Data on 146 Swedish and 79 Chinese children and their parents was available. Children, mothers and fathers in Stockholm were significantly more active than their counterparts in Wuhan (children; 2989 (SD 702) vs. 1997 (SD 899) counts per minute (CPM), mothers 2625 (SD 752) vs. 2042 (SD 821) CPM; fathers 2233 (SD 749) vs. 1588 (SD 754) CPM). Activity levels were similar over a week for children and parents within both countries. No parental-child correlations, except for a paternal-son correlation in Stockholm, were found. Children, mothers and fathers in Stockholm are more active compared with their counterparts in Wuhan. Interventions to increase physical activity needs to take cultural aspects into account, also when targeting very young children. PMID- 27404564 TI - Antigen Uptake during Different Life Stages of Zebrafish (Danio rerio) Using a GFP-Tagged Yersinia ruckeri. AB - Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were taken after 1 min, 15 min, 30 min, 2 h, 12 h and 24 h. At each sampling point fish were used for live imaging of the uptake using a fluorescence stereomicroscope and for immunohistochemistry (IHC). In adult fish, the bacterin could be traced within 30 min in scale pockets, skin, oesophagus, intestine and fins. Within two hours post bath (pb) Yr antigens were visible in the spleen and at 24 h in liver and kidney. Bacteria were associated with the gills, but uptake at this location was limited. Antigens were rarely detected in the blood and never in the nares. In juvenile fish uptake of the bacterin was seen in the intestine 30 min pb and in the nares 2 hpb but never in scale pockets. Antigens were detected in the spleen 12 hpb. Zebrafish larvae exhibited major Yr uptake only in the mid-intestine enterocytes 24 hpb. The different life stages of zebrafish varied with regard to uptake locations, however the gut was consistently a major uptake site. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion or bath vaccination, which points towards zebrafish as a suitable model organism for this aquacultured species. PMID- 27404567 TI - Category structure and processing in 6-year-old children with autism. AB - This study investigated the categorization abilities of 6-year-old children with autism spectrum disorders (ASD) as compared to their peers with typical development (TD) using a category verification task. We examined the impact of stimulus typicality on multiple aspects of real-time performance, including accuracy, reaction time, and performance stability. Both groups were more accurate in identifying typical category members than atypical ones; however, only the ASD group's accuracy was affected by item ordering, indicating less stable performance. Furthermore, category structure was predicted by concurrent language levels in the TD group but by concurrent nonverbal IQ in the ASD group; these latter two findings suggest that children with ASD process categories differently than their peers with TD. Autism Res 2017, 10: 327-336. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27404565 TI - Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position. AB - The use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, (1)H and (195)Pt NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis,cis,trans [Pt(NH3)2Cl2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed. PMID- 27404568 TI - Silver Complexes of Dihalogen Molecules. AB - The perfluorohexane-soluble and donor-free silver compound Ag(A) (A=Al(OR(F) )4 ; R(F) =C(CF3 )3 ) prepared using a facile novel route has unprecedented capabilities to form unusual and weakly bound complexes. Here, we report on the three dihalogen-silver complexes Ag(Cl2 )A, Ag(Br2 )A, and Ag(I2 )A derived from the soluble silver compound Ag(A) (characterized by single-crystal/powder XRD, Raman spectra, and quantum-mechanical calculations). PMID- 27404569 TI - An approach towards a perfect thermal diffuser. AB - A method for the most efficient removal of heat, through an anisotropic composite, is proposed. It is shown that a rational placement of constituent materials, in the radial and the azimuthal directions, at a given point in the composite yields a uniform temperature distribution in spherical diffusers. Such arrangement is accompanied by a very significant reduction of the source temperature, in principle, to infinitesimally above the ambient temperature and forms the basis for the design of a perfect thermal diffuser with maximal heat dissipation. Orders of magnitude enhanced performance, compared to that obtained through the use of a diffuser constituted from a single material with isotropic thermal conductivity has been observed and the analytical principles underlying the design were validated through extensive computational simulations. PMID- 27404571 TI - Risk of Ophthalmic Adverse Effects in Patients Treated with MEK Inhibitors: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: This meta-analysis aims to evaluate the risk of ophthalmic adverse effects associated with MEK inhibitors. METHODS: A literature search was conducted in PubMed and the Cochrane Library to identify randomized clinical trials (RCTs) which have been designed to evaluate the efficacy and safety of MEK inhibitors. Overall risk of ophthalmic adverse effects, chorioretinopathy, retinal detachment, blurred vision, uveitis, and eye haemorrhage were the assessed outcomes. Peto odds ratios (ORs) with their 95% confidence intervals (CIs) were pooled. Between-study heterogeneity was assessed using I2 statistics. RESULTS: Thirteen RCTs were included in this meta-analysis. Overall, MEK inhibitors were associated with an increased risk of ophthalmic adverse effects (OR 2.24; 95% CI 1.75-2.87; p < 0.0001; I2 = 86.5%). An increased risk was also estimated for chorioretinopathy (OR 5.44; 95% CI 2.89-10.23; p < 0.0001; I2 = 0%), retinal detachment (OR 6.54; 95% CI 3.28-13.03; p < 0.0001; I2 = 0%), and blurred vision (OR 2.30; 95% CI 1.50-3.54; p < 0.0001; I2 = 60.1%), but not for uveitis (OR 0.99; 95% CI 0.14-7.03; p = 0.991; I2 = 2.9%) or eye haemorrhage (OR 0.72; 95% CI 0.04-12.39; p = 0.824; I2 = 29.8%). CONCLUSIONS: Treatment with MEK inhibitors seems to increase the risk of ophthalmic adverse effects. A need for monitoring the safety of this class of drugs exists. Regulators, clinicians, and other health care professionals must, together, be involved in this process. PMID- 27404570 TI - Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction. AB - The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIalpha (pCaMKIIalpha) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 MUM/0.5 MUl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIalpha-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIalpha levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIalpha phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIalpha levels, the pCaMKIIalpha-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats. PMID- 27404572 TI - Cystinuria Associated with Different SLC7A9 Gene Variants in the Cat. AB - Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats. PMID- 27404574 TI - Inflammation severely alters thyroid hormone signaling in the central nervous system during experimental allergic encephalomyelitis in rat: Direct impact on OPCs differentiation failure. AB - Differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is severely impaired by inflammatory cytokines and this could lead to remyelination failure in inflammatory/demyelinating diseases. Due to the role of thyroid hormone in the maturation of OPCs and developmental myelination, in this study we investigated (i) the possible occurrence of dysregulation of thyroid hormone signaling in the CNS tissue during experimental neuroinflammation; (ii) the possible impact of inflammatory cytokines on thyroid hormone signaling and OPCs differentiation in vitro. The disease model is the experimental allergic encephalomyelitis in female Dark-Agouti rats, whereas in vitro experiments were carried out in OPCs derived from neural stem cells. The main results are the following: (i) a strong upregulation of cytokine mRNA expression level was found in the spinal cord during experimental allergic encephalomyelitis; (ii) thyroid hormone signaling in the spinal cord (thyroid hormone receptors; deiodinase; thyroid hormone membrane transporter) is substantially downregulated, due to the upregulation of the thyroid hormone inactivating enzyme deiodinase 3 and the downregulation of thyroid hormone receptors, as investigated at mRNA expression level; (iii) when exposed to inflammatory cytokines, deiodinase 3 is upregulated in OPCs as well, and OPCs differentiation is blocked; (iv) deiodinase 3 inhibition by iopanoic acid recovers OPCs differentiation in the presence on inflammatory cytokines. These data suggest that cellular hypothyroidism occurs during experimental allergic encephalomyelitis, possibly impacting on thyroid hormone-dependent cellular processes, including maturation of OPCs into myelinating oligodendrocytes. GLIA 2016;64:1573-1589. PMID- 27404573 TI - Potassium ions in extender differentially influence the post-thaw sperm motility of salmonid fish. AB - Potassium ions are known to have an inhibitory effect on the sperm motility of salmonids. For this reason, the addition of K(+) to the extender is frequently applied. However, the effect of the addition of K(+) to the extender has not yet been tested. The aim of this study was to test the influence of potassium ion supplementation of the extender on the sperm motility parameters from five Salmonidae species (rainbow trout (Oncorhynchus mykiss), sex-reversed female rainbow trout, whitefish (Coregonus lavaretus), brown trout (Salmo trutta) and brook trout (Salvelinus fontinalis)). Semen samples were diluted in extender containing 0.18 M glucose in 9% methanol (GM) supplemented with 0, 20 or 40 mM potassium chloride. After thawing sperm were stored for 30, 60, 120 and 240 min at 4 degrees C. Our results demonstrated that the presence of potassium ions in the extender had a negative effect on percentage of motile sperm in four of the salmonid species. In contrast, potassium ions appeared to have a positive effect on percentage of post-thaw motile sperm in whitefish semen. However, this effect could be mimicked by changing the osmolality of the extender (which was achieved by increasing the glucose concentration to 0.22 M). The addition of potassium ions turned out to have no positive effect on post-thaw storage time. Our results suggest that osmolality, rather than potassium ions, seems to be essential for cryopreservation success of salmonids sperm. Further studies should focus on the effects of small changes in osmolality on the post-thaw quality of semen. PMID- 27404575 TI - Improvements in stage of change correlate to changes in dietary intake and clinical outcomes in a 5-year lifestyle intervention in young high-risk Sri Lankans. AB - The objectives of a stage-matched approach to lifestyle change are that individuals progress forward through the stages of change. It also posits that progression through the stages of change is associated with positive changes in lifestyle behaviours. Measuring the relationship between stage of change and food intake is challenging due to the plurality of dietary behaviours. Furthermore, it is not clear whether changes in behaviour are sustained long-term. In this study we assess the movement through stages of change in the intensive (visits every 3months) and control groups (visits annually) of a large-scale primary prevention study in cardiovascular disease, carried out in 2637 children and young adults in Sri Lanka between 2007 and 2012. We also examine their relationship to dietary behaviours and clinical outcomes. We demonstrate that individuals in both groups continue to progress through stages of change over the course of the study and that measures of dietary behaviours improved from baseline to final follow-up. We also demonstrate that stage of change positively correlates to dietary behaviours including the ratio of recommended:not-recommended items, unpolished:polished starches and low-fat:high-fat food items throughout each year of the study. Finally, participants in the later stages of change at Y2, Y3 and Y4, had a significantly attenuated increase in weight and waist circumference at the final visit in both groups. We therefore demonstrate the usefulness of stage-matched approach in modifying complex dietary behaviours, and that stage of change is a valid measure of dietary behaviours across a large population over time. PMID- 27404576 TI - Portrayals of character smoking and drinking in Argentine-, Mexican- and US produced films. AB - The aim of this study was to assess film character portrayals of tobacco and alcohol use in US and nationally-produced films that were popular in Argentina and Mexico from 2004-2012. We performed a content analysis of these films (n=82 Argentine, 91 Mexican, and 908 US films, respectively). Chi-squares and t-tests were used to compare characteristics of characters who smoked or drank by country of movie production. Then data from all countries were pooled, and generalized estimating equation (GEE) models were used to determine independent correlates of character smoking or drinking. There were 480 major characters for Argentine-, 364 for Mexican-, and 4962 for US-produced films. Smoking prevalence among movie characters was similar to population smoking prevalence in Mexico (21%) and Argentina (26%), but about half in the US (11%), where movie product placements are restricted. Movie smoking declined over the period in all three countries. Movie alcohol prevalence was 40-50% across all countries and did not change with time. Demographic predictors of character smoking included: being male, 18 and older, having negative character valence. Movie smoking was not associated with lower SES. Predictors of character drinking included: being age 18 and older and positive character valence. Smoking and drinking predicted each other, illicit drug use, and higher scores for other risk behaviors. This suggests that policy development in Mexico and Argentina may be necessary to reduce the amount of character tobacco and alcohol use in films. PMID- 27404578 TI - Serum uric acid as a predictor of future hypertension: Stratified analysis based on body mass index and age. AB - BACKGROUND: Serum uric acid level is a predictor of future hypertension. However, its dependence on body mass index or age is unclear. METHODS: We examined 26,442 Japanese males aged 18-60years free from hypertension or diagnosed cardiovascular disease at baseline followed up between 2000 and 2010. Participants were categorized into three groups according to the tertile of serum uric acid levels [mg/dL; 1st (reference): 0.1-5.3; 2nd: 5.4-6.2; 3rd: 6.3-11.6]. Incident hypertension was defined as newly detected blood pressure>=140/90mmHg and/or antihypertensive drugs initiation. Body mass index (<25kg/m(2) vs. >=25kg/m(2)) and age (<40years vs. >=40years) were stratified into two groups. RESULTS: During a mean follow-up of 7.2years, there were 11,361 (43%) hypertension cases. Mean serum uric acid levels (mg/dL) at baseline in each group were 1st tertile, 4.6; 2nd tertile, 5.8; and 3rd tertile, 7.0. The cumulative incident hypertension rate was significantly higher in the 3rd tertile (50.8%) than in the 1st (37.4%). Multiple-adjusted hazard ratios (95% confidence interval) for incident hypertension compared with 1st tertile were 1.01 (0.96-1.05) and 1.15 (1.10-1.21) in the 2nd and 3rd tertile, respectively. There was a significant interaction between age and serum uric acid level (p for interaction=0.035). In subjects aged >=40years, the 3rd serum uric acid group showed higher hazard ratios [1.48 (1.38 1.59)]. CONCLUSION: High serum uric acid level was associated with future hypertension in young and middle-aged Japanese males. This association was stronger among subjects >=40years old. PMID- 27404577 TI - The role of neighborhood characteristics and the built environment in understanding racial/ethnic disparities in childhood obesity. AB - BACKGROUND: Childhood obesity prevalence remains high and racial/ethnic disparities may be widening. Studies have examined the role of health behavioral differences. Less is known regarding neighborhood and built environment mediators of disparities. The objective of this study was to examine the extent to which racial/ethnic disparities in elevated child body mass index (BMI) are explained by neighborhood socioeconomic status (SES) and built environment. METHODS: We collected and analyzed race/ethnicity, BMI, and geocoded address from electronic health records of 44,810 children 4 to 18years-old seen at 14 Massachusetts pediatric practices in 2011-2012. Main outcomes were BMI z-score and BMI z-score change over time. We used multivariable linear regression to examine associations between race/ethnicity and BMI z-score outcomes, sequentially adjusting for neighborhood SES and the food and physical activity environment. RESULTS: Among 44,810 children, 13.3% were black, 5.7% Hispanic, and 65.2% white. Compared to white children, BMI z-scores were higher among black (0.43units [95% CI: 0.40 0.45]) and Hispanic (0.38 [0.34-0.42]) children; black (0.06 [0.04-0.08]), but not Hispanic, children also had greater increases in BMI z-score over time. Adjusting for neighborhood SES substantially attenuated BMI z-score differences among black (0.30 [0.27-0.34]) and Hispanic children (0.28 [0.23-0.32]), while adjustment for food and physical activity environments attenuated the differences but to a lesser extent than neighborhood SES. CONCLUSIONS: Neighborhood SES and the built environment may be important drivers of childhood obesity disparities. To accelerate progress in reducing obesity disparities, interventions must be tailored to the neighborhood contexts in which families live. PMID- 27404579 TI - Spontaneous coronary artery dissection: new insights into diagnosis and treatment. AB - Spontaneous coronary artery dissection (SCAD) remains an infrequent, elusive, and challenging clinical entity of unknown etiology eight decades after its initial description. Our understanding of the pathophysiology of SCAD, initially limited to information from early pathological studies, case reports, and very short series, has been enriched recently by relatively large contemporary series of patients studied prospectively. The typical presentation involves a young woman without coronary risk factors suffering an acute coronary syndrome but, actually, most patients are middle-aged and have coronary risk factors. A high number of conditions have been related to SCAD, but fibromuscular dysplasia has shown a major intriguing association with potential pathophysiological implications. SCAD may present (a) with an intimal tear and the classic angiographic 'flap' leading to the appearance of two lumens (true and false), or (b) without an intimal rupture, as an intramural hematoma. An increased clinical awareness together with new diagnostic tools have led to a major surge in the diagnosis of SCAD. High resolution intracoronary techniques provide unique diagnostic insights into the underlying pathophysiology and facilitate identification of the disease in patients misdiagnosed previously. After the initial acute ischemic insult, most patients stabilize and have a benign clinical course and eventually experience spontaneous healing of the vessel wall during follow-up. However, recurrences may still occur in up to 10-20% of cases. Accordingly, a conservative medical management (watchful waiting strategy) has been recommended as the initial approach. Revascularization remains particularly challenging and may be associated with suboptimal results, acute complications, and poor long-term outcome. Nevertheless, in patients with ongoing or refractory ischemia and adequate anatomy, revascularization should be attempted. Some novel and attractive coronary interventions have been proposed in this uniquely challenging anatomic scenario. This review aims to present a comprehensive and contemporary update on this elusive and intriguing clinical entity. PMID- 27404580 TI - Long-circulatory nanoparticles for gemcitabine delivery: Development and investigation of pharmacokinetics and in-vivo anticancer efficacy. AB - The anticancer potential of gemcitabine, a nucleoside analog, is compromised due to the enzymatic degradation into inactive form leading to the short half-life in systemic circulation. Novel delivery strategies are required to improve therapeutic efficacy of this potential drug. Monomethoxy polyethylene glycol amine-polylactide-co-glycolide (mPEG-PLGA) co-polymer was synthesized and characterized by FTIR and (1)H NMR. Gemcitabine loaded mPEG-PLGA nanoparticles (NPs) were developed and investigated for pharmacokinetic profile and in vivo anticancer activity. The mPEG-PLGA NPs (size: 267+/-10nm, zeta potential: -17.5+/ 0.2mV) exhibited sustained drug release profile and were found to be compatible with blood. The mPEG-PLGA NPs were able to evade the uptake by macrophages (i.e. THP-1 and J774A) by reducing the adsorption of proteins on the surface of NPs. The enhanced cellular uptake and cell cytotoxicity was observed by mPEG-PLGA NPs in MiaPaCa-2 and MCF-7 cells. The half-life of gemcitabine in mPEG-PLGA NPs was remarkably enhanced (19 folds) than native gemcitabine. Further, the pharmacokinetic modulation of gemcitabine using mPEG-PLGA-NPs was translated in improved anticancer efficacy as compared to native gemcitabine in Ehrlich ascites bearing Balb-c mice. The results demonstrated the potential of long-circulatory nanoparticles in improving the pharmacokinetic profile and in-turn the anticancer efficacy of gemcitabine. PMID- 27404581 TI - Assay of Adhesion Under Shear Stress for the Study of T Lymphocyte-Adhesion Molecule Interactions. AB - Overall, T cell adhesion is a critical component of function, contributing to the distinct processes of cellular recruitment to sites of inflammation and interaction with antigen presenting cells (APC) in the formation of immunological synapses. These two contexts of T cell adhesion differ in that T cell-APC interactions can be considered static, while T cell-blood vessel interactions are challenged by the shear stress generated by circulation itself. T cell-APC interactions are classified as static in that the two cellular partners are static relative to each other. Usually, this interaction occurs within the lymph nodes. As a T cell interacts with the blood vessel wall, the cells arrest and must resist the generated shear stress.(1,2) These differences highlight the need to better understand static adhesion and adhesion under flow conditions as two distinct regulatory processes. The regulation of T cell adhesion can be most succinctly described as controlling the affinity state of integrin molecules expressed on the cell surface, and thereby regulating the interaction of integrins with the adhesion molecule ligands expressed on the surface of the interacting cell. Our current understanding of the regulation of integrin affinity states comes from often simplistic in vitro model systems. The assay of adhesion using flow conditions described here allows for the visualization and accurate quantification of T cell-epithelial cell interactions in real time following a stimulus. An adhesion under flow assay can be applied to studies of adhesion signaling within T cells following treatment with inhibitory or stimulatory substances. Additionally, this assay can be expanded beyond T cell signaling to any adhesive leukocyte population and any integrin-adhesion molecule pair. PMID- 27404582 TI - Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study. AB - OBJECTIVE: The objective was to compare, in a real-world setting, the risk of mental and physical health events associated with different antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine and first-generation antipsychotics) in patients with SZ. METHODS: This is a retrospective cohort study using administrative data. Outcome measures included any mental health event (suicide, hospitalization or emergency visit for mental disorders) and physical health event (death other than suicide, hospitalization or emergency visit for physical disorders). Cox proportional hazard models were used to estimate the hazard ratios of the events associated with the use of the different antipsychotic drugs. RESULTS: The cohort included 18 869 adult patients living in the province of Quebec (Canada) with SZ and starting antipsychotic drugs between January 1998 and December 2005. Results show that quetiapine and not using any antipsychotics were associated with an increased risk of mental and physical health events as compared to other drugs. The second finding is the confirmation of better performance of clozapine. The results were robust across sensitivity analyses. CONCLUSION: Both findings call for an international public health and drug agencies surveillance of 'real-world' antipsychotic medication to ensure the optimal choices in treatment guidelines for SZ. PMID- 27404584 TI - Synthesis and X-ray Crystallography of [Mg(H2O)6][AnO2(C2H5COO)3]2 (An = U, Np, or Pu). AB - Synthesis and X-ray crystallography of single crystals of [Mg(H2O)6][AnO2(C2H5COO)3]2, where An = U (I), Np (II), or Pu (III), are reported. Compounds I-III are isostructural and crystallize in the trigonal crystal system. The structures of I-III are built of hydrated magnesium cations [Mg(H2O)6](2+) and mononuclear [AnO2(C2H5COO)3](-) complexes, which belong to the AB(01)3 crystallochemical group of uranyl complexes (A = AnO2(2+), B(01) = C2H5COO(-)). Peculiarities of intermolecular interactions in the structures of [Mg(H2O)6][UO2(L)3]2 complexes depending on the carboxylate ion L (acetate, propionate, or n-butyrate) are investigated using the method of molecular Voronoi Dirichlet polyhedra. Actinide contraction in the series of U(VI)-Np(VI)-Pu(VI) in compounds I-III is reflected in a decrease in the mean An?O bond lengths and in the volume and sphericity degree of Voronoi-Dirichlet polyhedra of An atoms. PMID- 27404583 TI - Unraveling the Phosphocholination Mechanism of the Legionella pneumophila Enzyme AnkX. AB - The intracellular pathogen Legionella pneumophila infects lung macrophages and injects numerous effector proteins into the host cell to establish a vacuole for proliferation. The necessary interference with vesicular trafficking of the host is achieved by modulation of the function of Rab GTPases. The effector protein AnkX chemically modifies Rab1b and Rab35 by covalent phosphocholination of serine or threonine residues using CDP-choline as a donor. So far, the phosphoryl transfer mechanism and the relevance of observed autophosphocholination of AnkX remained disputable. We designed tailored caged compounds to make this type of enzymatic reaction accessible for time-resolved Fourier transform infrared difference spectroscopy. By combining spectroscopic and biochemical methods, we determined that full length AnkX is autophosphocholinated at Ser521, Thr620, and Thr943. However, autophosphocholination loses specificity for these sites in shortened constructs and does not appear to be relevant for the catalysis of the phosphoryl transfer. In contrast, transient phosphocholination of His229 in the conserved catalytic motif might exist as a short-lived reaction intermediate. Upon substrate binding, His229 is deprotonated and locked in this state, being rendered capable of a nucleophilic attack on the pyrophosphate moiety of the substrate. The proton that originated from His229 is transferred to a nearby carboxylic acid residue. Thus, our combined findings support a ping-pong mechanism involving phosphocholination of His229 and subsequent transfer of phosphocholine to the Rab GTPase. Our approach can be extended to the investigation of further nucleotidyl transfer reactions, which are currently of reemerging interest in regulatory pathways of host-pathogen interactions. PMID- 27404585 TI - Penetration of Oxidized Carbon Nanospheres through Lipid Bilayer Membrane: Comparison to Graphene Oxide and Oxidized Carbon Nanotubes, and Effects of pH and Membrane Composition. AB - Here we show that the ability of oxidized carbon particles to penetrate phospholipid bilayer membrane varies with the particle shapes, chemical functionalities on the particle surface, lipid compositions of the membrane and pH conditions. Among the similar surface charged oxidized carbon particles of spherical (oxidized carbon nanosphere, OCS), tubular (oxidized carbon nanotube, OCT), and sheet (oxidized graphene sheet, OGSh) morphologies, OCS possesses the highest levels of adhesion to lipid bilayer membrane and penetration into the cell-sized liposome. OCS preferably binds better to the disordered lipid bilayer membrane (consisting of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) as compared to the ordered membrane (consisting of 1,2-dipalmitoyl-sn-glycero-3 phosphatidylcholine and cholesterol). The process of OCS-induced leak on the membrane is pH responsive and most pronounced under an acidic condition. Covalently decorating the OCS's surface with poly(ethylene oxide) or (2 aminoethyl)trimethylammonium moieties decreases its ability to interact with the membrane. When used as carriers, OCSs can deliver curcumin into nucleus of A549 human lung cancer and human embryonic kidney cells, in contrast, curcumin molecules delivered by OCTs remain in the cytoplasm. OGShs cannot significantly enter cells and cannot induce noticeable cellular uptake of curcumin. PMID- 27404586 TI - Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy. AB - BACKGROUND: Interstitial brachytherapy for localised prostate cancer may be followed by transient increases in prostate-specific antigen (PSA) that resolve without therapy. Such PSA bounces may be associated with an improved outcome but often cause alarm in the patient and physician, and have defied explanation. METHODS: We developed a mathematical model to capture the interactions between the tumour, radiation and anti-tumour immune response. The model was fitted to data from a large cohort of patients treated exclusively with interstitial brachytherapy. Immunohistological analysis for T-cell infiltration within the same tumours was also performed. RESULTS: Our minimal model captures well the dynamics of the tumour after therapy, and suggests that a strong anti-tumour immune response coupled with the therapeutic effect of radiation on the tumour is responsible for the PSA bounce. Patients who experience a PSA bounce had a higher density of CD3 and CD8 cells within the tumour that likely contribute to the PSA bounce and the overall better outcomes observed. CONCLUSIONS: Our observations provide a novel and unifying explanation for the PSA bounce in patients with early prostate cancer and also have implications for the use of immune-based therapies in such patients to improve outcomes. PMID- 27404587 TI - Topical Administration of Acylated Homoserine Lactone Improves Epithelialization of Cutaneous Wounds in Hyperglycaemic Rats. AB - Clinicians often experience delayed epithelialization in diabetic patients, for which a high glucose condition is one of the causes. However, the mechanisms underlying delayed wound closure have not been fully elucidated, and effective treatments to enhance epithelialization in patients with hyperglycaemia have not been established. Here we propose a new reagent, acylated homoserine lactone (AHL), to improve the delayed epithelialization due to the disordered formation of a basement membrane of epidermis in hyperglycaemic rats. Acute hyperglycaemia was induced by streptozotocin injection in this experiment. Full thickness wounds were created on the flanks of hyperglycaemic or control rats. Histochemical and immunohistochemical analyses were performed to identify hyperglycaemia-specific abnormalities in epidermal regeneration by comparison between groups. We then examined the effects of AHL on delayed epithelialization in hyperglycaemic rats. Histological analysis showed the significantly shorter epithelializing tissue (P < 0.05), abnormal structure of basement membrane (fragmentation and immaturity), and hypo- and hyperproliferation of basal keratinocytes in hyperglycaemic rats. Treating the wound with AHL resulted in the decreased abnormalities of basement membrane, normal distribution of proliferating epidermal keratinocytes, and significantly promoted epithelialization (P < 0.05) in hyperglycemic rats, suggesting the improving effects of AHL on abnormal epithelialization due to hyperglycemia. PMID- 27404589 TI - The professionalization of scientific research. PMID- 27404599 TI - Spatial and Temporal Spread of Acute Viral Respiratory Infections in Young Children Living in High-altitude Rural Communities: A Prospective Household-based Study. AB - BACKGROUND: Few studies have described patterns of transmission of viral acute respiratory infections (ARI) in children in developing countries. We examined the spatial and temporal spread of viral ARI among young children in rural Peruvian highland communities. Previous studies have described intense social interactions in those communities, which could influence the transmission of viral infections. METHODS: We enrolled and followed children <3 years of age for detection of ARI during the 2009 to 2011 respiratory seasons in a rural setting with relatively wide geographic dispersion of households and communities. Viruses detected included influenza, respiratory syncytial virus (RSV), human metapneumovirus and parainfluenza 2 and 3 viruses (PIV2, PIV3). We used geospatial analyses to identify specific viral infection hot spots with high ARI incidence. We also explored the local spread of ARI from index cases using standard deviational ellipses. RESULTS: Geospatial analyses revealed hot spots of high ARI incidence around the index cases of influenza outbreaks and RSV outbreak in 2010. Although PIV3 in 2009 and PIV2 in 2010 showed distinct spatial hot spots, clustering was not in proximity to their respective index cases. No significant aggregation around index cases was noted for other viruses. Standard deviational ellipse analyses suggested that influenza B and RSV in 2010, and human metapneumovirus in 2011 spread temporally in alignment with the major road network. CONCLUSIONS: Despite the geographic dispersion of communities in this rural setting, we observed a rapid spread of viral ARI among young children. Influenza strains and RSV in 2010 had distinctive outbreaks arising from their index cases. PMID- 27404588 TI - Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster. AB - Notch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila, the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo. PMID- 27404600 TI - Evaluation of the Ganglion Cell Complex and Retinal Nerve Fiber Layer in Low, Moderate, and High Myopia: A Study by RTVue Spectral Domain Optical Coherence Tomography. AB - PURPOSE: To assess the effect of low, moderate, and high myopia on the thickness of the retinal nerve fiber layer (RNFL) and Ganglion cell complex (GCC) measured by Spectral Domain Optical Coherence Tomography (SD-OCT) in non-glaucomatous subjects. METHODS: The subjects were divided into three groups: low (n = 81, 35.6%), moderate (n = 79, 34.8%), and highly myopic eyes (n = 67, 29.5%). The RNFL thickness profile, including the average, superior, nasal, inferior, and temporal quadrant and each of the eight directional thicknesses, was measured. GCC parameters, including the average, superior, and inferior values, the focal loss volume (FLV), and the global loss volume (GLV), were measured. The correlation between the OCT measurements and the axial length was evaluated. RESULTS: The average, superior, inferior, and nasal RNFL thicknesses of low and moderate myopic eyes were found to be significantly higher than those of highly myopic eyes. The temporal RNFL thicknesses were not different among the three groups. The average, superior, and inferior ganglion cell complex values of low and moderate myopic eyes were significantly higher than those of highly myopic eyes. The FLV and GLV of low and moderate myopic eyes were significantly higher than those of highly myopic eyes (p = 0.001 for all). In the moderate and high myopia groups, the average RNFL thickness and GCC thickness were both negatively correlated with the axial length. CONCLUSION: Highly myopic subjects tend to have thinner RNFL and GCC thicknesses than subjects with low and moderate myopia. PMID- 27404602 TI - Secular Change in Morphological Pelvic Traits used for Sex Estimation. AB - This research evaluates secular change in Phenice's (Am J Phys Anthropol, 30, 1969 and 297) three morphological traits of the pubis, as described by Klales et al. (Am J Phys Anthropol, 149, 2012 and 104): medial aspect of the ischio-pubic ramus, subpubic contour, and ventral arc. Ordinal scores were collected for these traits and compared between a sample of innominates from the historical Hamann Todd Collection (n = 170) and modern Bass Donated Collection (n = 129). Using the Freeman-Halton test, significant differences between temporal sample score frequencies were found for all traits in females and for the subpubic contour and ventral arc in males. Despite these findings, classification accuracy using logistic regression between the temporal periods remained low (68.7%). These results suggest that secular changes in trait expression are occurring; however, sex estimation methods using these traits and created with historical samples are still applicable to modern forensic cases. In fact, the secular changes occurring in these traits contribute to better classification accuracy between sexes in modern populations. PMID- 27404603 TI - The Stone Cold Truth: The Effect of Concrete Encasement on the Rate and Pattern of Soft Tissue Decomposition. AB - This study provides a descriptive analysis of taphonomic changes observed in the soft tissue of ten pigs (Sus scrofa) after being encased in Quickrete ((r)) concrete and excavated at monthly or bimonthly intervals over the course of 2 years. The best method of subject excavation was investigated. Rate and pattern of decomposition were compared to a nonencased control subject. Results demonstrate subjects interred in concrete decomposed significantly slower than the control subject (p < 0.01), the difference being observable after 1 month. After 1 year, the encased subject was in the early stage of decomposition with purging fluids and intact organs present, versus complete skeletonization of the control subject. Concrete subjects also display a unique decomposition pattern, exhibiting a chemically burned outer layer of skin and a common separation of the dermal and epidermal layers. Results suggest using traditional methods to estimate postmortem interval on concrete subjects may result in underestimation. PMID- 27404604 TI - Long-term Geophysical Monitoring of Simulated Clandestine Graves using Electrical and Ground Penetrating Radar Methods: 4-6 Years After Burial. AB - This ongoing monitoring study provides forensic search teams with systematic geophysical data over simulated clandestine graves for comparison to active cases. Simulated "wrapped," "naked," and "control" burials were created. Multiple geophysical surveys were collected over 6 years, here showing data from 4 to 6 years after burial. Electrical resistivity (twin electrode and ERI), multifrequency GPR, grave and background soil water were collected. Resistivity surveys revealed that the naked burial had low-resistivity anomalies up to year four but then difficult to image, whereas the wrapped burial had consistent large high-resistivity anomalies. GPR 110- to 900-MHz frequency surveys showed that the wrapped burial could be detected throughout, but the naked burial was either not detectable or poorly resolved. 225-MHz frequency GPR data were optimal. Soil water analyses showed decreasing (years 4 to 5) to background (year 6) conductivity values. Results suggest both resistivity and GPR surveying if burial style unknown, with winter to spring surveys optimal and increasingly important as time increases. PMID- 27404605 TI - Latent Fingermark Aging Patterns (Part I): Minutiae Count as One Indicator of Degradation. AB - The authors are exploring degradation patterns of latent fingermarks over time which can be quantitatively determined in a predictable manner by visual means. Several physical degradation parameters for assessing this hypothesis are evaluated. This article analyzes the parameter "minutiae count" as a function of time. Experiment variables included were secretion type (sebaceous-rich and eccrine-rich), substrate (glass and plastic), and exposure to light (dark, shade, and direct light). Depositions were sequentially visualized with Titanium Dioxide powder over a period of 6 months, photographed, and number of minutiae recorded. Results revealed a significant decrease of minutiae for eccrine-rich marks on glass but insignificant for sebaceous-rich marks on the same surface. However, significant degradation was observed for both types of secretions on plastic. The authors conclude that the distinctive prevalence of minutiae changes over time indicates with a high degree of certainty the hypothesis is valid and deserves additional exploration. PMID- 27404606 TI - An Approach to Speaker Identification. AB - This presentation will provide standards upon which any attempts to meet the challenge of identifying speakers by voice should be based. It is organized into a model based on (i) application of a rigorous research program validating the system, (ii) an upgrading of the organization of the SI area, and (iii) exploitation of new technology. The second part of the presentation will describe an illustrative speech/voice approach to SI development. This effort is also based on an extensive corpus of research. It is suggested that application of the cited standards, plus the illustrative model, will permit reasonable progress to be made. Finally, a number of procedural recommendations are made; they should enhance the efficacy of the proposed approach. PMID- 27404607 TI - Economic and Sociological Correlates of Suicides: Multilevel Analysis of the Time Series Data in the United Kingdom. AB - For the effects of social integration on suicides, there have been different and even contradictive conclusions. In this study, the selected economic and social risks of suicide for different age groups and genders in the United Kingdom were identified and the effects were estimated by the multilevel time series analyses. To our knowledge, there exist no previous studies that estimated a dynamic model of suicides on the time series data together with multilevel analysis and autoregressive distributed lags. The investigation indicated that unemployment rate, inflation rate, and divorce rate are all significantly and positively related to the national suicide rates in the United Kingdom from 1981 to 2011. Furthermore, the suicide rates of almost all groups above 40 years are significantly associated with the risk factors of unemployment and inflation rate, in comparison with the younger groups. PMID- 27404608 TI - Concordance Rate for the Identification of Distant Entrance Gunshot Wounds of the Back by Experienced Forensic Pathologists Examining Only Images of Autopsies. AB - The images of 66 gunshot entrance wounds with a defect on the back, a bullet in the body, hemorrhage along the wound track, and logical certainty that it was an entrance wound were collected from the files of a moderately busy medical examiner's office. Participants numbering 22 board-certified forensic pathologists viewed a single digital archival image of each of the 66 entrance wounds randomly mixed with 74 presumptive exit wounds to determine whether they were entrance or exit wounds. The concordance rate for correctly identifying the 66 logically known entrance wounds was 82.8% with a range from 58% to 97%. This pilot study was conducted to provide an evidence-based approach to the interpretation of the direction of gunshot wounds by reviewing pathologists with access only to archival photographs, and it is not a measure of the accuracy to distinguish entrance from exit wounds when given all of the circumstances. PMID- 27404609 TI - One Hundred and One Cases of Plastic Bag Suffocation in the Milan Area Between 1993 and 2013-Correlations, Circumstances, Pathological and Forensic Evidences and Literature Review. AB - Plastic Bag Suffocation is a rare cause of death in developed countries and almost unknown in the rest of the world. This study aims to retrospectively evaluate cases of PBS _asphyxia in Milan's Department of Legal Medicine from 1993 to 2013. Cases were selected from the database of 21,472 autopsies performed in the considered timeframe. One hundred and one cases were considered to be cases of Plastic Bag Suffocation, comprised of 100 suicides, no accidental events and 1 homicide. The most relevant elements pertaining to this type of death were evaluated for both the corpses and the crime scenes. From this study the typical PBS victim is an adult male, aged 52.3 years on average, depressed or afflicted by chronic or terminal diseases, and found at home. In 42.6% of cases, the victims were found with the plastic bag still positioned over their head, fastened by tying. Also common among these cases are drugs, alcohol and chemical abuses. According to the collected data, it is impossible to outline a pathognomonic detrimental background that leads to this cause of death. Crime scene investigation is, therefore, the one and only technical resource for evaluating these cases. PMID- 27404610 TI - Bacterial Translocation and Sample Contamination in Postmortem Microbiological Analyses. AB - The diagnostic value of postmortem bacteriology has been discussed controversially for decades. In the study herein, contamination during sampling procedures and postmortem translocation were investigated to interpret postmortem microbiology results. One hundred medicolegal autopsy cases in total were included. Radiology, histology, bacteriology, and biochemistry were performed in all cases. Based on all investigation findings, 4 groups of cases were identified: death unrelated to infection, true infections, false positive (contamination during sampling procedures, postmortem translocation and mixed situations), and undetermined. The results of this study indicate that postmortem bacteriology provides useful data supporting infection-related deaths, especially when potentially significant observations are accompanied by consistent autopsy, histology, and biochemistry. Result interpretation requires careful evaluation of number and type of isolated microorganisms. PMID- 27404611 TI - Relationship Between Self-Injurious Behaviors and Levels of Aggression in Children and Adolescents Who Were Subject to Medicolegal Examination. AB - Aggression, which is defined as a behavior causing harm or pain, is a behavioral pattern typically expected in children and adolescents who are involved in criminal activities. The aim of this study was to examine the relationship between aggression and self-injurious behavior (SIB) in children and adolescents. The study was performed in 295 cases which were sent for medicolegal examination. The mean age of the subjects was 14.27 +/- 1.05 years (age range 10-18 years). The aggression levels of the subjects were determined using the Aggression Questionnaire (AQ), which is an updated form of the Buss-Durkee Hostility Inventory. The mean total AQ score of the subjects with and without SIB was 78.04 +/- 21.0 and 62.75 +/- 18.05, respectively (p < 0.01). There were significant statistical differences between the two groups with respect to their subscale scores (p < 0.01). It was concluded that the levels of aggression increased in children and adolescents who were involved in criminal activities when the SIBs increased. PMID- 27404612 TI - Decisional Capacity to Consent to Clinical Research Involving Placebo in Psychiatric Patients. AB - Evidence from a few studies indicates the existence of several issues related to psychiatric patients' decisional capacity to give informed consent to clinical research. Clinicians often face difficulties in acquiring valid informed consent in clinical practice and even more so in drug trials. Participants often fail to fully understand or retain information regarding the actual implications of research protocols. The Brief Assessment for Consent to Clinical Research (BACO) was developed to investigate capacity to consent to clinical trials and further compare patients with schizophrenia and healthy comparisons' decisional capacity. A method to avoid possible confounding effects of choosing a treatment regarding a current disease was applied. The study groups were administered the BACO and the MacArthur Competence Assessment Tool for Clinical Research. Psychiatric patients performed poorer in comprehending, appreciating, and reasoning abilities, than their healthy counterparts. Impaired cognitive functioning and psychiatric symptoms severity were associated with reduced capacity to consent. PMID- 27404613 TI - Bidimensional Data Allow for Better Age Estimation on Immature Specimens than Unidimensional Data: A Preliminary Study on the Ilium. AB - Most biometric age estimation methods used in anthropological and forensic science for juveniles are based on unidimensional measurements (length or width). Here, a new method using bidimensional data was tested. A 3D morphometric analysis was performed on 108 CT scans of ilium bone of juveniles (from 20 gestational weeks to 12 years old). The sample was divided into training and validation groups. Best predictors were determined by comparing the efficiency of each variable (length, width, area, and module: a product of length and width). We established linear and polynomial regressions for each parameter for both sides. Applying the equations to the validation sample showed no significant difference between real and predicted ages. For age estimation, the area and module parameters yielded better results than unidimensional measurements. The results from this preliminary study were highly conclusive, and it would be interesting to extend the work, covering larger samples, and other bones. PMID- 27404614 TI - Automated Classification of Epiphyses in the Distal Radius and Ulna using a Support Vector Machine. AB - The aim of this study was to automatically classify epiphyses in the distal radius and ulna using a support vector machine (SVM) and to examine the accuracy of the epiphyseal growth grades generated by the support vector machine. X-ray images of distal radii and ulnae were collected from 140 Chinese teenagers aged between 11.0 and 19.0 years. Epiphyseal growth of the two elements was classified into five grades. Features of each element were extracted using a histogram of oriented gradient (HOG), and models were established using support vector classification (SVC). The prediction results and the validity of the models were evaluated with a cross-validation test and independent test for accuracy (PA ). Our findings suggest that this new technique for epiphyseal classification was successful and that an automated technique using an SVM is reliable and feasible, with a relative high accuracy for the models. PMID- 27404615 TI - A Procedure for Calculating the Vertical Space Height of the Sacrum When Determining Skeletal Height for Use in the Anatomical Method of Adult Stature Estimation. AB - Estimating stature from skeletonized remains is one of the essential parameters in the development of a biological profile. A new procedure for determining skeletal height (SKH) incorporating the vertical space height (VSH) from the anterior margin of the sacral promontory to the superior margins of the acetabulae for use in the anatomical method of stature estimation is introduced. Regression equations for stature estimation were generated from measurements of 38 American males of European ancestry from the William M. Bass Donated Skeletal Collection. The modification to the procedure results in a SKH that is highly correlated with stature (r = 0.925-0.948). Stature estimates have low standard errors of the estimate ranging from 21.79 to 25.95 mm, biases from to 0.50 to 0.94 mm, and accuracy rates from 17.71 mm to 19.45 mm. The procedure for determining the VSH, which replaces "S1 height" in traditional anatomical method models, is a key improvement to the method. PMID- 27404616 TI - Effects of Aluminum Foil Packaging on Elemental Analysis of Bone. AB - Burned skeletal material is often very fragile and at high risk for fragmentation during packaging and transportation. One method that has been suggested to protect bones in these cases is to carefully wrap them in aluminum foil. Traces of aluminum, however, are known to transfer from foil packaging materials to food products. If such transfer occurs between aluminum foil and bones, it could interfere with subsequent chemical, elemental and isotopic analyses, which are becoming more common in forensic anthropological investigations. This study examined aluminum levels in bones prior to and following the use of aluminum foil packaging and storage for a 6-week period. Results indicate no significant change in the detected levels of aluminum (p > 0.05), even when packaged in compromised foil and exposed to elevated temperatures. Aluminum foil can therefore continue to be recommended as a packaging medium without affecting subsequent chemical examinations. PMID- 27404617 TI - The Effect of Time on Bone Fluorescence: Implications for Using Alternate Light Sources to Search for Skeletal Remains. AB - Bones fluoresce when exposed to certain wavelengths of shortwave light, and this property can be useful in locating and sorting skeletal remains in forensic contexts. The proteins in bone collagen are largely responsible for its fluorescent properties, but these proteins degrade and denature over time. This study examined the fluorescence of bones from four temporal groups (recent, semi recent, ancient, and historic) ranging from 0 to 1064 years before present. Specimens were photographed under 490 nm wavelength light, and fluorescence was quantified by converting intensity to a gray scale value based on the RGB color model using ImageJ((r)) software. Significant (p < 0.05) differences were found in mean fluorescence between all four temporal groups, and a 0.324 coefficient of correlation indicates a significant (inverse) relationship between fluorescence and time. Bone fluorescence decreases with time, but some fluorescence is retained even in older samples. Fluorescence can therefore be reliably used in many modern skeletal remains searches. PMID- 27404618 TI - Interobserver Reliability of the Total Body Score System for Quantifying Human Decomposition. AB - Several authors have tested the accuracy of the Total Body Score (TBS) method for quantifying decomposition, but none have examined the reliability of the method as a scoring system by testing interobserver error rates. Sixteen participants used the TBS system to score 59 observation packets including photographs and written descriptions of 13 human cadavers in different stages of decomposition (postmortem interval: 2-186 days). Data analysis used a two-way random model intraclass correlation in SPSS (v. 17.0). The TBS method showed "almost perfect" agreement between observers, with average absolute correlation coefficients of 0.990 and average consistency correlation coefficients of 0.991. While the TBS method may have sources of error, scoring reliability is not one of them. Individual component scores were examined, and the influences of education and experience levels were investigated. Overall, the trunk component scores were the least concordant. Suggestions are made to improve the reliability of the TBS method. PMID- 27404619 TI - An Appraisal of Decomposition Cases Received at the Johannesburg Forensic Pathology Service Medico-legal Mortuary During 2010-2011. AB - Decomposed bodies pose many questions for researchers regarding environmental effects, cause of death, and patterns. This study aimed to observe the factors associated with decomposed bodies autopsied at the Johannesburg Forensic Pathology Service Medico-legal Mortuary. A total of 4876 autopsies were conducted from 2010 to 2011, of which 109 were decomposed. Black individuals made up the largest proportion (67%) followed by White (26%). Males comprised 86.2%, while 12.8% were female. The mean age was 42.78 years. Most cases were in the early stages of decomposition (49.5%), with 32.1% bloated, 11.9% in active decay, 2.8% in advanced decay, and 3.7% were skeletal. Insect activity was identified in 25.7% of decomposition cases. Cause of death was determined in 48.6% of cases. Of all the cases, 64% were found indoors and 23% outdoors, while 23% had insufficient information regarding the location. Of considerable interest was the number of cases from hospitals and clinics. PMID- 27404620 TI - Investigation into Seasonal Scavenging Patterns of Raccoons on Human Decomposition. AB - Although raccoons are known as one of the most common scavengers in the U.S., scavenging by these animals has seldom been studied in terms of forensic significance. In this research, the seasonal pattern of raccoon scavenging and its effect on human decomposition was investigated using 178 human cadavers placed at the Anthropological Research Facility (ARF) of the University of Tennessee, Knoxville (UTK) between February 2011 and December 2013. The results reveal that (i) the frequency of scavenging increases during summer, (ii) scavenging occurs relatively immediately and lasts shorter in summer months, and (iii) scavenging influences the decomposition process by hollowing limbs and by disturbing insect activities, both of which eventually increases the chance of mummification on the affected body. This information is expected to help forensic investigators identify raccoon scavenging as well as make a more precise interpretation of the effect of raccoon scavenging on bodies at crime scenes. PMID- 27404621 TI - High-throughput Sequencing of Trace Quantities of Soil Provides Reproducible and Discriminative Fungal DNA Profiles. AB - High-throughput sequencing (HTS) offers improved resolution between forensic soil samples by characterizing individual taxa present; however, the heterogeneous distribution of taxa in soils, and limited quantity of material available, may hinder the reliability of HTS in casework. Using HTS of the internal transcribed spacer, we examined the effect of soil mass (50, 150, and 250 mg) on fungal DNA profiles, focusing on reproducibility and discriminatory power between close proximity soils, and samples with similar textural classification. The results show that reduced soil mass had no significant effect on sample differentiation and that 150 mg soil provides the most reproducible DNA profiles across different soil types. In addition, Ascomycota was identified as a robust fungal target for forensic intelligence as this phylum was detected consistently across all samples regardless of sample quantity. Overall, this study highlights the value of trace quantities of soil for use in forensic casework. PMID- 27404622 TI - Nondestructive Biological Evidence Collection with Alternative Swabs and Adhesive Lifters. AB - In forensic science, biological material is typically collected from evidence via wet/dry double swabbing with cotton swabs, which is effective but can visibly damage an item's surface. When an item's appearance must be maintained, dry swabbing and tape-lifting may be employed as collection techniques that are visually nondestructive to substrates' surfaces. This study examined the efficacy of alternative swab matrices and adhesive lifters when collecting blood and fingerprints from glass, painted drywall, 100% cotton, and copy paper. Data were evaluated by determining the percent profile and quality score for each STR profile generated. Hydraflock((r)) swabs, BVDA Gellifters((r)) , and Scenesafe FASTTM tape performed as well as or better than cotton swabs when collecting fingerprints from painted drywall and 100% cotton. Collection success was also dependent on the type of biological material sampled and the substrate on which it was deposited. These results demonstrated that alternative swabs and adhesive lifters can be effective for nondestructive DNA collection from various substrates. PMID- 27404623 TI - Applications of Blue Light-curing Acrylic Resin to Forensic Sample Preparation and Microtomy. AB - This study discusses the results of an evaluation of a one-part blue light-curing acrylic resin for embedding trace evidence prior to the preparation of thin sections with a microtome. Through a comparison to several epoxy resins, the physical properties relevant to both trace evidence examination and analytical microscopy in general, including as viscosity, clarity, color, hardness, and cure speed, were explored. Finally, thin sections from paint samples embedded in this acrylic resin were evaluated to determine if, through smearing or impregnation, the resin contributed to the infrared spectra. The results of this study show that blue light-curing acrylic resins provide the desired properties of an embedding medium, generate high-quality thin sections, and can significantly simplify the preparation of paint chips, fibers and a multitude of other types of microscopic samples in the forensic trace evidence laboratory. PMID- 27404624 TI - Use of Embryos Extracted from Individual Cannabis sativa Seeds for Genetic Studies and Forensic Applications. AB - Legal limits on the psychoactive tetrahydrocannabinol (THC) content in Cannabis sativa plants have complicated genetic and forensic studies in this species. However, Cannabis seeds present very low THC levels. We developed a method for embryo extraction from seeds and an improved protocol for DNA extraction and tested this method in four hemp and six marijuana varieties. This embryo extraction method enabled the recovery of diploid embryos from individual seeds. An improved DNA extraction protocol (CTAB3) was used to obtain DNA from individual embryos at a concentration and quality similar to DNA extracted from leaves. DNA extracted from embryos was used for SSR molecular characterization in individuals from the 10 varieties. A unique molecular profile for each individual was obtained, and a clear differentiation between hemp and marijuana varieties was observed. The combined embryo extraction-DNA extraction methodology and the new highly polymorphic SSR markers facilitate genetic and forensic studies in Cannabis. PMID- 27404625 TI - An Impact Velocity Device Design for Blood Spatter Pattern Generation with Considerations for High-Speed Video Analysis. AB - A mechanical device that uses gravitational and spring compression forces to create spatter patterns of known impact velocities is presented and discussed. The custom-made device uses either two or four springs (k1 = 267.8 N/m, k2 = 535.5 N/m) in parallel to create seventeen reproducible impact velocities between 2.1 and 4.0 m/s. The impactor is held at several known spring extensions using an electromagnet. Trigger inputs to the high-speed video camera allow the user to control the magnet's release while capturing video footage simultaneously. A polycarbonate base is used to allow for simultaneous monitoring of the side and bottom views of the impact event. Twenty-four patterns were created across the impact velocity range and analyzed using HemoSpat. Area of origin estimations fell within an acceptable range (DeltaXav = -5.5 +/- 1.9 cm, DeltaYav = -2.6 +/- 2.8 cm, DeltaZav = +5.5 +/- 3.8 cm), supporting distribution analysis for the use in research or bloodstain pattern training. This work provides a framework for those interested in developing a robust impact device. PMID- 27404626 TI - Dimensional Review of Scales for Forensic Photography. AB - Scales for photography provide a geometrical reference in the photographic documentation of a crime scene, pattern, or item of evidence. The ABFO No. 2 Standard Reference Scale (1) is used by the forensic science community as an accurate reference scale. We investigated the overall accuracy of the major centimeter graduations, internal/external diameters of the circles, error in placement of the circle centers, and leg perpendicularity. Four vendors were selected for the scales, and the features were measured on a vision-based coordinate measurement system. The scales were well within the specified tolerance for the length graduations. After 4 years, the same scales were measured to determine what change could be measured. The scales demonstrated acceptable stability in the scale length and center-to-center measurements; however, the perpendicularity exhibited change. The study results indicate that scale quality checks using certified metal rulers are good practice. PMID- 27404627 TI - Fast Source Camera Identification Using Content Adaptive Guided Image Filter. AB - Source camera identification (SCI) is an important topic in image forensics. One of the most effective fingerprints for linking an image to its source camera is the sensor pattern noise, which is estimated as the difference between the content and its denoised version. It is widely believed that the performance of the sensor-based SCI heavily relies on the denoising filter used. This study proposes a novel sensor-based SCI method using content adaptive guided image filter (CAGIF). Thanks to the low complexity nature of the CAGIF, the proposed method is much faster than the state-of-the-art methods, which is a big advantage considering the potential real-time application of SCI. Despite the advantage of speed, experimental results also show that the proposed method can achieve comparable or better performance than the state-of-the-art methods in terms of accuracy. PMID- 27404628 TI - Time-dependent Expression of MMP-2 and TIMP-2 after Rats Skeletal Muscle Contusion and Their Application to Determine Wound Age. AB - The ability to determine vitality and estimate the survival period after a wound is critical in routine forensic practice. The mRNA levels of MMP-2 and TIMP-2 were examined using quantitative real-time RT-PCR to determine the age of a wound. Furthermore, the colocalization of them with Macrophage Marker, respectively, was detected by double immunofluorescence, and a standardized rat model of skeletal muscle contusion was established. In the antemortem contused groups, a large number of macrophages showed positive staining for MMP-2 and TIMP 2, and the expression of MMP-2 and TIMP-2 mRNA increased sharply at 3 days postinjury, with relative quantities of 5.75 and 2.98. No samples in the other groups showed relative quantities of >5.75 and 2.98; therefore, relative quantities exceeding 5.75 and 2.98 were strongly indicated 3 days after contusion. In addition, there was a significant decrease in the relative quantity in the postmortem contused groups, indicating that they were useful for diagnosing vitality. PMID- 27404630 TI - Sudden Death Caused by Anomalous Origin of the Coronary Artery During Exercise. AB - Anomalous origin of the coronary artery (AOCA) is a rare, but important cause of sudden cardiac death among young athletes. Nine autopsy cases (8 male, 1 female; mean age, 17.9 years; age range, 11-31 years) of sudden death during or just after exercise caused by AOCA were reviewed. The exercises performed at the time of death were running (4 cases), soccer (2 cases), and baseball, swimming and kendo (Japanese swordsmanship) (1 case each). In 6 cases, the left coronary artery arose from the right sinus of Valsalva, and in 3, the right coronary artery from the left sinus. The coronary arteries passed between the pulmonary artery and the aorta with an acute angle takeoff from the orifice. Three cases had cardiovascular manifestations prior to death. In cases with cardiovascular manifestations, novel imaging methods should be considered to prevent sudden death. PMID- 27404629 TI - Forensic Analysis of a Contact Lens in a Murder Case. AB - Contact lenses have had rare relevance in trials and/or investigations. After 5 years of burial, orbital remnants were retrieved from an exhumed body and subsequently identified as a key piece of material evidence in a murder trial. The exhumed case materials were evaluated under laboratory conditions and were determined to be contact lens remnants. Contact lens fracture and burial simulation studies were performed to provide additional corroboration of the physical findings of the exhumed contact lens remnants. This material evidence was instrumental in providing factual proof refuting the defendant's testimony in the murder trial. A brief history of contact lens composition and use is provided for understanding the methods and observational results. This forensic case study represents the first published documentation of a contact lens from an exhumed body being used in a murder investigation and establishes an operational procedure for future forensic contact lens examinations. PMID- 27404631 TI - Inferior Vena Cava Tumor Thrombosis Secondary to Metastatic Uterine Cancer: A Rare Cause of Sudden Unexpected Death. AB - Pulmonary tumor thromboembolus (PTTE) secondary to uterine cancer is a rare cause of sudden unexpected deaths in the elderly population. Additionally, tumor extension to the inferior vena cava (IVC) makes it rarer. No such cases have been previously reported in the forensic literature. We report this phenomenon in a previously healthy 70-year-old woman with no other known risk factors for the development of deep vein thrombosis. The deceased was found dead while watching television with her relatives. Autopsy examination revealed that her death was attributed to a saddle embolus lodged in the main pulmonary arteries. A uterine tumor was discovered, and microscopic examination revealed low-grade endometrial stromal sarcoma with angiolymphatic invasion. The tumor cells were also found in the embolus and the remnant thrombosis attached to the inner wall of the IVC. This case demonstrates a sudden unexpected death caused by acute PTTE following seeding of uterine cancer into the IVC and raises awareness of such events. PMID- 27404632 TI - Homicidal Snake Bite in Children. AB - Snake bites are common in many regions of the world. Snake envenomation is relatively uncommon in Egypt; such unfortunate events usually attract much publicity. Snake bite is almost only accidental, occurring in urban areas and desert. Few cases were reported to commit suicide by snake. Homicidal snake poisoning is so rare. It was known in ancient world by executing capital punishment by throwing the victim into a pit full of snakes. Another way was to ask the victim to put his hand inside a small basket harboring a deadly snake. Killing a victim by direct snake bite is so rare. There was one reported case where an old couple was killed by snake bite. Here is the first reported case of killing three children by snake bite. It appeared that the diagnosis of such cases is so difficult and depended mainly on the circumstantial evidences. PMID- 27404633 TI - Pitfalls in the Interpretation of Traumatic Socioethnic Practices. AB - The purpose of this case study was to raise awareness among forensic pathologists and medicolegal death investigators regarding two unique socioethnic practices and regional customs that have significant forensic implications. We present two cases involving coining (gua sha) and bloodletting (sapi) that represent two forms of traditional customs that involve the use of blunt force and sharp force trauma, respectively. In coining, the skin lesions are produced as a result of dermabrasion with oils and oval objects such as coin. In sapi, multiple superficial linear scrapes are made in the skin as part of a bloodletting ceremony. The identification of these lesions will prevent the interpretation of them as non-voluntary-inflicted trauma. PMID- 27404634 TI - Embutramide, a Component of Tanax((r)) (T-61) as a New Drug of Abuse? AB - Tanax((r)) (T-61) is a euthanasia solution commonly used in veterinary medicine in Europe. It consists of three active components: embutramide, mebezonium iodide, and tetracaine hydrochloride. Human consumption of Tanax((r)) (T-61) is usually associated with suicide attempts. In our 15-year-long practice, embutramide was detected only three times but within a short period. First, it was found in the urine of a 42-year-old veterinarian, and the other two observations were made in a 16-year-old young man. Urine samples were analyzed using Shimadzu Prominence TOX.I.S.II. HPLC-DAD system with online SPE extraction system. Both of the two patients denied any intention to die. These cases show that this veterinary drug may also be considered as potential drugs of abuse. PMID- 27404635 TI - Measurement of Carbon Dioxide Production from Radiolabeled Substrates in Drosophila melanogaster. AB - The power of Drosophila genetics is increasingly being applied to questions of hormone signaling and metabolism and to the development of models of human disease in this organism. Sensitive methods for measurements of parameters such as metabolic rates are needed to drive the understanding of physiology and disease in small animals such as the fruit fly. The method described here assesses fuel oxidation in small numbers of adult flies fed food containing trace amounts of (14)C-labeled substrates such as glucose or fatty acid. After the feeding period and any additional experimental manipulations, flies are transferred to short tubes capped with mesh, which are then placed in glass vials containing KOH-saturated filter paper that traps exhaled, radiolabeled CO2 generated from oxidation of radiolabeled substrates as potassium bicarbonate, KHCO3. This radiolabeled bicarbonate is measured by scintillation counting. This is a quantitative, reproducible, and simple approach for the study of fuel oxidation. The use of radiolabeled glucose, fatty acids, or amino acids allows determination of the contribution of these different fuel sources to energy metabolism under different conditions such as feeding and fasting and in different genetic backgrounds. This complements other approaches used to measure in vivo energy metabolism and should further the understanding of metabolic regulation. PMID- 27404638 TI - Which is More Dangerous: International Terrorism or Secondhand Smoke? PMID- 27404636 TI - An Integrated Analysis of MicroRNA and mRNA Expression Profiles to Identify RNA Expression Signatures in Lambskin Hair Follicles in Hu Sheep. AB - Wave patterns in lambskin hair follicles are an important factor determining the quality of sheep's wool. Hair follicles in lambskin from Hu sheep, a breed unique to China, have 3 types of waves, designated as large, medium, and small. The quality of wool from small wave follicles is excellent, while the quality of large waves is considered poor. Because no molecular and biological studies on hair follicles of these sheep have been conducted to date, the molecular mechanisms underlying the formation of different wave patterns is currently unknown. The aim of this article was to screen the candidate microRNAs (miRNA) and genes for the development of hair follicles in Hu sheep. Two-day-old Hu lambs were selected from full-sib individuals that showed large, medium, and small waves. Integrated analysis of microRNA and mRNA expression profiles employed high throughout sequencing technology. Approximately 13, 24, and 18 differentially expressed miRNAs were found between small and large waves, small and medium waves, and medium and large waves, respectively. A total of 54, 190, and 81 differentially expressed genes were found between small and large waves, small and medium waves, and medium and large waves, respectively, by RNA sequencing (RNA-seq) analysis. Differentially expressed genes were classified using gene ontology and pathway analyses. They were found to be mainly involved in cell differentiation, proliferation, apoptosis, growth, immune response, and ion transport, and were associated with MAPK and the Notch signaling pathway. Reverse transcription-polymerase chain reaction (RT-PCR) analyses of differentially expressed miRNA and genes were consistent with sequencing results. Integrated analysis of miRNA and mRNA expression indicated that, compared to small waves, large waves included 4 downregulated miRNAs that had regulatory effects on 8 upregulated genes and 3 upregulated miRNAs, which in turn influenced 13 downregulated genes. Compared to small waves, medium waves included 13 downregulated miRNAs that had regulatory effects on 64 upregulated genes and 4 upregulated miRNAs, which in turn had regulatory effects on 22 downregulated genes. Compared to medium waves, large waves consisted of 13 upregulated miRNAs that had regulatory effects on 48 downregulated genes. These differentially expressed miRNAs and genes may play a significant role in forming different patterns, and provide evidence for the molecular mechanisms underlying the formation of hair follicles of varying patterns. PMID- 27404639 TI - Different Types of Sedentary Activities and Their Association With Perceived Health and Wellness Among Middle-Aged and Older Adults: A Cross-Sectional Analysis. AB - PURPOSE: To assess the association between a variety of sedentary activities and self-reported wellness outcomes to provide a comprehensive perspective for future development of sedentary guidelines for middle-aged and older adults. DESIGN: Cross-sectional population study. SETTING: Canadian Community Health Survey (Healthy Aging Cycle, 2008-2009). SUBJECTS: Middle-aged (45-60 years; n = 8161) and older adults (60 years and older; n = 9128) were used for analysis. MEASURES: Self-reported perceived health, sense of belonging to community, mood disorder, and satisfaction with life were used as outcomes. Sedentary activities were playing bingo, computer use, doing crosswords/puzzles, handicrafts, listening to radio/music, playing a musical instrument, reading, visiting others, and watching TV. ANALYSIS: Chi-squares, t-tests and multivariable logistic regressions. RESULTS: Among respondents not diagnosed with a mood disorder, positive associations were noted for crosswords/puzzles in older adults (odds ratio [OR]: 1.39, confidence interval [CI]: 1.01-1.91) and listening to radio/music or playing an instrument in middle-aged adults (OR: 1.43, CI: 1.16-1.75; OR: 2.14, CI: 1.17-3.81). Satisfaction with life was positively associated with computer use in middle-aged (OR: 1.53, CI: 1.07-2.20) and older adults (OR: 1.42, CI: 1.09 1.84). Sense of belonging was consistently positively associated with sedentary activities. CONCLUSION: Several sedentary activities were found to be positively associated with self-reported measures of psychosocial wellness in middle-aged and older adults. These findings identify potential opportunities for sedentary time interventions and dual-task physical activity promotion. PMID- 27404640 TI - Does Dog Walking Predict Physical Activity Participation: Results From a National Survey. AB - PURPOSE: The purpose of this study is to: (1) identify characteristics associated with dog owners who walk their dog, (2) describe the frequency and duration of walking the dog, and (3) determine whether dog owners who walk their dog participate in more physical activity than dog owners who do not walk their dog and non-dog owners. DESIGN: A cross-sectional study design was used. SETTING: The study setting was nationwide. SUBJECTS: Adults (n = 4010) participating in the 2005 ConsumerStyles mail-panel survey were the study subjects. MEASURES: Measures used were demographic, physical activity, dog ownership, and dog walking questions from the 2005 ConsumerStyles mail-panel survey. ANALYSIS: Chi-square tests and analyses of variance were conducted to examine participant characteristics associated with dog walking and to describe the frequency and duration of dog walking. Analysis of covariance was used to determine whether dog owners who walk their dog participate in more physical activity than dog owners who do not walk their dog and non-dog owners. RESULTS: Among dog owners, 42% reported some dog walking in a typical week. Dog owners walked their dog an average 4.3 +/- 0.1 times and 128.8 +/- 5.6 minutes per week. There were no significant differences in weekly minutes of moderate or vigorous physical activity across the dog-ownership and dog walking groups. CONCLUSION: Most dog owners did not walk their dog. Dog owners were not more active than non-dog owners, except when considering the activity obtained via dog walking. PMID- 27404641 TI - Health Behavior Combinations and Their Association With Inflammation. AB - PURPOSE: Studies have examined the independent and additive effects of health behaviors (e.g., physical activity, diet, sleep, and smoking) on systemic inflammation, but we know little about whether different pairs of these behaviors differentially influence inflammation, which was the purpose of this study. DESIGN: Cross-sectional. SETTING: The National Health and Nutrition Examination Survey (NHANES) 2005-2006. SUBJECTS: A total of 2051 adults (>=20 years). MEASURES: A questionnaire/interview was used to assess sleep and dietary behavior; physical activity was assessed via accelerometry; smoking was assessed via cotinine levels; and a blood sample was taken to assess systemic inflammation (C-reactive protein; [CRP]). ANALYSIS: Multivariable linear regression analysis. RESULTS: Six health behavior pairs were evaluated: (1) active and healthy diet, (2) active and adequate sleep, (3) active and nonsmoker, (4) healthy diet and adequate sleep, (5) healthy diet and nonsmoker, and (6) adequate sleep and nonsmoker. After adjusting for age, gender, race-ethnicity, poverty level, and chronic disease, only active and nonsmoker (beta = -.15) and healthy diet and adequate sleep (beta = -.16) were associated with CRP. CONCLUSION: Regular physical activity and smoking avoidance and healthy eating and adequate sleep were the two health behavior pairs associated with less inflammation. This suggests that certain health behaviors may act synergistically on reducing systemic inflammation, whereas other health behavior combinations may not. Such knowledge may help to develop and implement tailored health behavior interventions. PMID- 27404642 TI - Randomized Clinical Trial of the Women's Lifestyle Physical Activity Program for African-American Women: 24- and 48-Week Outcomes. AB - PURPOSE: To compare the effects of a physical activity (PA) intervention of group meetings versus group meetings supplemented by personal calls or automated calls on the adoption and maintenance of PA and on weight stability among African American women. DESIGN: Randomized clinical trial with three conditions randomly assigned across six sites. SETTING: Health settings in predominately African American communities. SUBJECTS: There were 288 women, aged 40 to 65, without major signs/symptoms of pulmonary/cardiovascular disease. INTERVENTION: Six group meetings delivered over 48 weeks with either 11 personal motivational calls, 11 automated motivational messages, or no calls between meetings. MEASURES: Measures included PA (questionnaires, accelerometer, aerobic fitness), weight, and body composition at baseline, 24 weeks, and 48 weeks. ANALYSIS: Analysis of variance and mixed models. RESULTS: Retention was 90% at 48 weeks. Adherence to PA increased significantly (p < .001) for questionnaire (d = .56, 128 min/wk), accelerometer (d = .37, 830 steps/d), and aerobic fitness (d = .41, 7 steps/2 min) at 24 weeks and was maintained at 48 weeks (p < .001), with no differences across conditions. Weight and body composition showed no significant changes over the course of the study. CONCLUSION: Group meetings are a powerful intervention for increasing PA and preventing weight gain and may not need to be supplemented with telephone calls, which add costs and complexity. PMID- 27404643 TI - Spice MyPlate: Nutrition Education Focusing Upon Spices and Herbs Improved Diet Quality and Attitudes Among Urban High School Students. AB - PURPOSE: To determine whether an experiential nutrition education intervention focusing on spices and herbs ("Spice MyPlate") is feasible and improves diet quality and healthy eating attitudes among an urban and predominantly African American sample of adolescents more than standard nutrition education alone. DESIGN: A nonrandomized controlled trial compared standard nutrition education in U.S. Department of Agriculture MyPlate guidelines (control group) with standard nutrition education plus adjuvant Spice MyPlate curriculum (intervention group). Data were collected at baseline and after 3, 6, and 10 weeks. SETTING: Study setting was two public high schools in Baltimore, Maryland. SUBJECTS: A total of 110 students in grades 9 to 12 participated. INTERVENTION: The 6-week school based intervention conducted during health class focused on cooking using spices and herbs to eat healthier diets according to MyPlate. MEASURES: Dietary intake reported on 3-day food records and healthy eating attitudes questionnaires was analyzed. ANALYSIS: Differences in diet quality and healthy eating attitudes between study groups were estimated by t-tests, Wilcoxon-Mann-Whitney tests, and covariate-adjusted regression models. RESULTS: Spice MyPlate was feasible and there were modest but significant improvements (p <= .05) in the Spice MyPlate group compared with control in whole grains (31.2 g/wk) and protein foods (13.2 ounces per week) intake, and attitudes toward eating vegetables, whole grains, lean protein, and low-fat dairy. CONCLUSIONS: Although randomized trials are needed, experiential nutrition education focusing on spices and herbs may help urban and predominantly African-American adolescent populations eat healthier diets. PMID- 27404644 TI - Association Between Sugar-Sweetened Beverage Intake and Proxies of Acculturation Among U.S. Hispanic and Non-Hispanic White Adults. AB - PURPOSE: This study examined associations between sugar-sweetened beverage (SSB) intake and acculturation among a sample representing civilian noninstitutionalized U.S. adults. DESIGN: Quantitative, cross-sectional study. SETTING: National. SUBJECTS: The 2010 National Health Interview Survey data for 17,142 Hispanics and U.S.-born non-Hispanic whites (>=18 years). MEASURES: The outcome variable was daily SSB intake (nondiet soda, fruit drinks, sports drinks, energy drinks, and sweetened coffee/tea drinks). Exposure variables were Hispanic ethnicity and proxies of acculturation (language of interview, birthplace, and years living in the United States). ANALYSIS: We used multivariate logistic regression to estimate adjusted odds ratios (ORs) for the exposure variables associated with drinking SSB >=1 time/d after controlling for covariates. RESULTS: The adjusted odds of drinking SSB >=1 time/d was significantly higher among Hispanics who completed the interview in Spanish (OR = 1.65) than U.S.-born non-Hispanic whites. Compared with those who lived in the United States for <5 years, the adjusted odds of drinking SSB >=1 time/d was higher among adults who lived in the United States for 5 to <10 years (OR = 2.72), those who lived in the United States for 10 to <15 years (OR = 2.90), and those who lived in the United States for >=15 years (OR = 2.41). However, birthplace was not associated with daily SSB intake. CONCLUSION: The acculturation process is complex and these findings contribute to identifying important subpopulations that may benefit from targeted intervention to reduce SSB intake. PMID- 27404645 TI - Baseline Predictors of Singular Action Among Participants With Multiple Health Behavior Risks. AB - PURPOSE: Previous studies found that treatment effects can change two behaviors, but not one. This study examined baseline transtheoretical model constructs as three alternative predictors (stage of change, effort, and severity) of singular action among participants with co-occurring health behavior risks. DESIGN: The study examined participants at risk for three pairs of behaviors (sun and smoking; smoking and diet; and diet and sun). Analyses were conducted with participants who changed only one behavior in a pair (singular action). SETTING: School and home-based behavior change programs recruited participants via schools, worksites, and physician practices. School, worksite, medical, and home based prevention programs were the study setting. SUBJECTS: The sample (N = 3213) was age 44.6 years (SD, 11.1 years), 94.6% white, and 63.7% female. MEASURES: Stages of change, effort, and severity variables were measured. ANALYSIS: Pooled data were analyzed using logistic regressions from three randomized controlled trials. RESULTS: Across all three behaviors, stage of change, effort, and severity effects were consistently related to behavior change at 24 months. Change efforts on one behavior were related to change on another behavior. Baseline sun severity (odds ratio, .97 [.94, 1.00]; p = .046) and smoking severity (odds ratio, .89 [.80, .98]; p = .019) were significant predictors of change on diet at final follow-up. CONCLUSION: Stage of change was the biggest predictor. Problem severity was the smallest predictor of change at 2-year follow up. Four of six predictors were within behaviors, whereas two were between. PMID- 27404646 TI - The Impact of a National Tobacco Education Campaign on State-Specific Quitline Calls. AB - PURPOSE: The ads from the first federally funded national tobacco education campaign, Tips From Former Smokers (Tips), considerably increased quitline calls nationwide. This study evaluates the effect of Tips on state-specific quitline calls. DESIGN: Precampaign, during-campaign, and postcampaign comparison; regression modeling. SETTING: All fifty states as well as the District of Columbia. SUBJECTS: Calls to state quitlines. INTERVENTION: Tips. MEASURES: Tips campaign exposure was measured by gross rating points (GRPs). Calls to quitline's 1-800-QUIT-NOW were assigned to markets in each state based on their area codes. ANALYSIS: Multivariate regression was used to assess the relationship between calls to state quitlines and media market-level Tips GRPs, while controlling for market and area code characteristics. RESULTS: Nationally, every 100 Tips GRPs per week at the market level was associated with an average of 45 additional quitline calls in each area code (beta = 44.65, p < .001). Tips GRPs were associated with significant increases in quitline calls in 46 states and the District of Columbia, of which 11 experienced effects significantly larger than the national average and 5 experienced significantly smaller effects. We were unable to detect statistically significant effects of GRPs on call volumes for four states. Graphically, call volumes in those states followed Tips GRPs. CONCLUSION: The Tips campaign significantly increased calls to quitlines for almost all the states. These findings underscore the effectiveness of national tobacco media campaigns for reaching state audiences. PMID- 27404647 TI - The Experience With Smoke-Free Policies in Affordable Multiunit Housing in North Carolina: A Statewide Survey. AB - PURPOSE: Previous surveys of housing operators have identified concerns about enforcement, legal issues, and loss of market share as the main barriers to implementing smoke-free policies in multiunit housing. The purpose of this study was to examine enforcement practices as well as economic and legal outcomes in smoke-free affordable multiunit housing. DESIGN: Cross-sectional. SETTING: Affordable multiunit housing in North Carolina. SUBJECTS: Affordable multiunit housing properties (n = 1063, 57% response rate). MEASURES: Property representatives completed a written survey with questions regarding the existence of smoke-free policies, smoke-free policy implementation and enforcement practices, and smoking-related costs. ANALYSIS: Descriptive statistics, chi(2) goodness-of-fit test, and t-test. RESULTS: A total of 16.5% of properties had policies that prohibited smoking in all residential units. Half (49.8%) of smoke free properties reported no violations to their policies in the past 12 months. Legal actions to enforce policies were rarely needed and were successful when they did occur. Compared to smoking-allowed properties, smoke-free properties did not experience a loss of market share in terms of occupancy rate (t = .09; p = .93) or residents moving away (chi(2) =. 5; p = .48). CONCLUSION: Housing operators' concerns about enforcement, legal issues, and loss of market share associated with smoke-free policies are largely unfounded among affordable housing properties in North Carolina. Public health professionals should use messaging strategies that refute these concerns to encourage more properties to adopt smoke-free policies. PMID- 27404648 TI - From the Classroom to Facebook: A Fresh Approach for Youth Tobacco Prevention. AB - PURPOSE: The explosive rise in Internet use calls for effective ways to utilize new forms of social media to enhance school smoking prevention programs. We attempted to design and test an educational intervention for youth tobacco prevention. DESIGN: Intervention design and posttest pilot implementation. SETTING: A single high school in Athens, Greece. SUBJECTS: Two hundred twenty five students (aged 15-18 years). INTERVENTION: A Facebook-integrated educational intervention in six simple steps was designed and tested during an ad hoc smoking prevention lecture to high school students in Greece in order to stimulate social mobilization in online networks. MEASURES: Number of students with an active Facebook account, percentage posting antismoking messages within a 72-hour period, number of Facebook friends reached. ANALYSIS: Descriptive statistics. RESULTS: Assessed 3 days after the lecture, 15.9% of students had posted a smoking-related sentence in their Facebook account, a take-home message that was spread as a note on their wall via news feed to their 20,095 cumulative Facebook friends. CONCLUSION: One smoking-related take-home message can spread virally to a large number of adolescents through their Facebook friends. This intervention provides insight into a novel way of providing health information to youth, a hard-to-reach and vulnerable population. PMID- 27404649 TI - The Art of Health Promotion ideas for improving health outcomes. PMID- 27404650 TI - An Interview with Wolf Kirsten and Bob Karch. PMID- 27404651 TI - Workplace Health in the UK. PMID- 27404652 TI - Paradigm Shift in Workplace Health in Singapore: From Awareness to Behavior Change. PMID- 27404653 TI - The International Health Promotion Issue-The Australian Perspective. PMID- 27404654 TI - Conflict, Consequences, and the Inexorable Influence of Culture. PMID- 27404655 TI - CREB-mediated synaptogenesis and neurogenesis is crucial for the role of 5-HT1a receptors in modulating anxiety behaviors. AB - Serotonin 1a-receptor (5-HT1aR) has been specifically implicated in the pathogenesis of anxiety. However, the mechanism underlying the role of 5-HT1aR in anxiety remains poorly understood. Here we show in mice that the transcription factor cAMP response element binding protein (CREB) in the hippocampus functions as an effector of 5-HT1aR in modulating anxiety-related behaviors. We generated recombinant lentivirus LV-CREB133-GFP expressing a dominant negative CREB which could not be phosphorylated at Ser133 to specifically reduce CREB activity, and LV-VP16-CREB-GFP expressing a constitutively active fusion protein VP16-CREB which could be phosphorylated by itself to specifically enhance CREB activity. LV CREB133-GFP neutralized 5-HT1aR agonist-induced up-regulation of synapse density, spine density, dendrite complexity, neurogenesis, and the expression of synapsin and spinophilin, two well-characterized synaptic proteins, and abolished the anxiolytic effect of 5-HT1aR agonist; whereas LV-VP16-CREB-GFP rescued the 5 HT1aR antagonist-induced down-regulation of synapse density, spine density, dendrite complexity, neurogenesis and synapsin and spinophilin expression, and reversed the anxiogenic effect of 5-HT1aR antagonist. The deletion of neurogenesis by irradiation or the diminution of synaptogenesis by knockdown of synapsin expression abolished the anxiolytic effects of both CREB and 5-HT1aR activation. These findings suggest that CREB-mediated hippoacampus structural plasticity is crucial for the role of 5-HT1aR in modulating anxiety-related behaviors. PMID- 27404656 TI - The first clinical experience with a novel directional coronary atherectomy catheter: Preliminary Japanese multicenter experience. AB - AIMS: Despite development of drug eluting stents (DES), percutaneous coronary intervention (PCI) for bifurcation lesions using DES alone remains challenging. The aim of this study was to report on the initial clinical experience with a novel directional coronary atherectomy (DCA) catheter. METHODS AND RESULTS: Patients with de novo bifurcation lesions were entered into a prospective registry and a novel DCA catheter was used. Device, procedural success and in hospital outcomes were evaluated. A total of 14 patients with bifurcation lesions were enrolled. DCA was performed successfully in all cases without any major procedure-related events (device success rate: 100%, procedural success rate: 100%). Four patients (29%) were treated without stent implantation and simple stenting was achieved in the other 10 patients. No in-hospital major adverse cardiac event was observed. CONCLUSIONS: PCI with a novel DCA catheter for bifurcation lesions may be safe and effective. The clinical significance of these findings needs to be determined in future studies. This study was performed to evaluate the safety and efficacy of a novel directional coronary atherectomy catheter for bifurcation lesions. Both the device and procedural success rates were 100%. Complex stenting could be avoided in all cases. No inhospital major adverse cardiac event was observed. The novel directional coronary atherectomy catheter may be safe and effective for bifurcation lesions, even in this drug eluting stent era. (c) 2016 Wiley Periodicals, Inc. PMID- 27404657 TI - Photochemical Degradation of Various Bridge-Substituted Fluorene-Based Materials. AB - Photochemical degradation is an important issue to be overcome in advancing the lifetime of fluorene-containing conjugated polymers. In order to optimize the inertness of the materials, a quantitative measure for the efficiency of degradation is needed. Here, we introduce a method to measure a relative quantum yield of the photochemical degradation by monitoring the kinetics of the process by means of UV/vis spectroscopy and liquid chromatography (LC) techniques. This method is employed to a set of differently substituted 2,7-diphenylfluorenes, serving as model compounds for polyfluorene materials. Our measurements show that the quantum yield changes by orders of magnitude upon varying the bridge substituents and that altered kinetics indicate changing degradation mechanisms. PMID- 27404658 TI - Oligomers of N-Substituted beta(2)-Homoalanines: Peptoids with Backbone Chirality. AB - A new class of peptoid-based peptidomimetics composed of oligomers of N substituted beta(2)-homoalanines is reported. Design, solid-phase synthesis, and preliminary circular dichroism studies of oligomers of N-alkylated beta(2) homoalanines consisting of up to 8-mers are described. PMID- 27404659 TI - Optical vortex beam generator at nanoscale level. AB - Optical beams carrying orbital angular momentum (OAM) can find tremendous applications in several fields. In order to apply these particular beams in photonic integrated devices innovative optical elements have been proposed. Here we are interested in the generation of OAM-carrying beams at the nanoscale level. We design and experimentally demonstrate a plasmonic optical vortex emitter, based on a metal-insulator-metal holey plasmonic vortex lens. Our plasmonic element is shown to convert impinging circularly polarized light to an orbital angular momentum state capable of propagating to the far-field. Moreover, the emerging OAM can be externally adjusted by switching the handedness of the incident light polarization. The device has a radius of few micrometers and the OAM beam is generated from subwavelength aperture. The fabrication of integrated arrays of PVLs and the possible simultaneous emission of multiple optical vortices provide an easy way to the large-scale integration of optical vortex emitters for wide-ranging applications. PMID- 27404660 TI - Detection of a Novel qnrB19-Carrying Plasmid Variant Mediating Decreased Fluoroquinolone Susceptibility in Salmonella enterica Serovar Hadar. AB - Thirty Salmonella enterica subsp. enterica serovar Hadar isolates of avian origin collected between 2007 and 2010 from chicken carcasses in five geographically spread abattoirs in Germany were investigated for plasmid-mediated quinolone resistance determinants. Four isolates were identified by PCR analysis and hybridization experiments to carry qnrB genes. The isolates were indistinguishable by their XbaI macrorestriction patterns and did not exhibit a mutation in the quinolone resistance-determining regions of the DNA gyrase and topoisomerase IV genes. The qnrB genes were found to be located on small plasmids of ~2.6 kb, which mediated decreased susceptibility only to quinolones. The plasmids were assigned to the same type, pHAD28, and transformation studies into an Escherichia coli recipient strain confirmed their transferability. Sequence analysis of the complete plasmid pHAD28 revealed the presence of a qnrB19 gene. The gene was found on a novel variant of qnrB19-harboring plasmids with high similarity to plasmids pPAB19-3 from E. coli and pPAB19-4 from Salmonella sp. M9397. A presumptive recombination side was detected, suggesting that interplasmid recombination events might have played a role in the development of this plasmid variant. PMID- 27404661 TI - Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients. AB - Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants. PMID- 27404662 TI - Identification and Validation of SNP Markers Linked to Dwarf Traits Using SLAF Seq Technology in Lagerstroemia. AB - The genetic control of plant architecture is a promising approach to breed desirable cultivars, particularly in ornamental flowers. In this study, the F1 population (142 seedlings) derived from Lagerstroemia fauriei (non-dwarf) * L. indica 'Pocomoke' (dwarf) was phenotyped for six traits (plant height (PH), internode length (IL), internode number, primary lateral branch height (PLBH), secondary lateral branch height and primary branch number), and the IL and PLBH traits were positively correlated with the PH trait and considered representative indexes of PH. Fifty non-dwarf and dwarf seedlings were pooled and subjected to a specific-locus amplified fragment sequencing (SLAF-seq) method, which screened 1221 polymorphic markers. A total of 3 markers segregating between bulks were validated in the F1 population, with the M16337 and M38412 markers highly correlated with the IL trait and the M25207 marker highly correlated with the PLBH trait. These markers provide a predictability of approximately 80% using a single marker (M25207) and a predictability of 90% using marker combinations (M16337 + M25207) in the F1 population, which revealed that the IL and the PLBH traits, especially the PLBH, were the decisive elements for PH in terms of molecular regulation. Further validation was performed in the BC1 population and a set of 28 Lagerstroemia stocks using allele-specific PCR (AS-PCR) technology, and the results showed the stability and reliability of the SNP markers and the co-determination of PH by multiple genes. Our findings provide an important theoretical and practical basis for the early prediction and indirect selection of PH using the IL and the PLBH, and the detected SNPs may be useful for marker assisted selection (MAS) in crape myrtle. PMID- 27404664 TI - Rickettsiae and rickettsial diseases in Croatia: Implications for travel medicine. AB - AIM: To review the current state of knowledge concerning rickettsiae and rickettsioses in Croatia and to discuss their implications for travellers. METHODS: The PubMed database was searched from 1991 to 2015 by combining the words "rickettsia," "rickettsiosis", "travellers" and "Croatia". RESULTS: Since 1969, Croatia appears to be free of epidemic typhus (ET) caused by Rickettsia prowazekii and the last case of Brill-Zinsser disease was recorded in 2008. Mediterranean spotted fever (MSF) caused by Rickettsia conorii is the most frequent human rickettsial infection in Croatia, followed by murine typhus caused by Rickettsia typhi. Human cases of MSF and murine typhus have been predominantly observed along the eastern Adriatic coast from Zadar to Dubrovnik and between Zadar and Split, respectively. Rickettsia akari, etiologic agent of rickettsialpox, was isolated from blood of a patient diagnosed with MSF in Zadar, but no cases of rickettsialpox were reported. Several species of pathogenic (Rickettsia slovaca, Rickettsia aeschlimannii, Ricketsia helvetica, and Ricketsia raoultii) and species of undetermined pathogenicity (Ricketsia hoogstraalii sp. nov.) rickettsiae were identified in ticks collected in different ecological regions of Croatia. A search of the literature revealed no evidence of rickettsial infection in travellers visiting Croatia. Three imported cases of Rickettsia africae were observed in travellers returning from South Africa. CONCLUSION: Rickettsiae and rickettsial diseases continue to be present in Croatia. As they can be acquired while travelling, physicians should consider rickettsial infection in the differential diagnosis of patients returning from Croatia and presenting with febrile illness. PMID- 27404665 TI - Zika virus infection in two travelers returning from an epidemic area to Italy, 2016: Algorithm for diagnosis and recommendations. PMID- 27404663 TI - Community Willingness to Participate in a Dengue Study in Aceh Province, Indonesia. AB - BACKGROUND: Dengue virus infection is the most rapidly spreading vector-borne disease in the world. Essential research on dengue virus transmission and its prevention requires community participation. Therefore, it is crucial to understand the factors that are associated with the willingness of communities in high prevalence areas to participate in dengue research. The aim of this study was to explore factors associated with the willingness of healthy community members in Aceh province, Indonesia, to participate in dengue research that would require phlebotomy. METHODOLOGY/PRINCIPAL FINDINGS: A community-based cross sectional study was carried out in nine regencies and municipalities of Aceh from November 2014 to March 2015. Interviews using a set of validated questionnaires were conducted to collect data on demography, history of dengue infection, socioeconomic status, and knowledge, attitude and practice regarding dengue fever. Two-step logistic regression and Spearman's rank correlation (rs) analysis were used to assess the influence of independent variables on dependent variables. Among 535 participants, less than 20% had a good willingness to participate in the dengue study. The factors associated with good willingness to participate were being female, working as a civil servant, private employee or entrepreneur, having a high socioeconomic status and good knowledge, attitude and practice regarding dengue. Good knowledge and attitude regarding dengue were positive independent predictors of willingness to participate (OR: 2.30 [95% CI: 1.36-3.90] and 3.73 [95% CI: 2.24-6.21], respectively). CONCLUSION/SIGNIFICANCE: The willingness to participate in dengue research is very low among community members in Aceh, and the two most important associated factors are knowledge and attitude regarding dengue. To increase participation rate, efforts to improve the knowledge and attitude of community members regarding dengue fever and dengue related research is required before such studies are launched. PMID- 27404666 TI - Oxazolidines as Intermediates in the Asymmetric Synthesis of 3-Substituted and 1,3-Disubstituted Tetrahydroisoquinolines. AB - A diastereoselective mercury(II)-promoted intramolecular cyclization of unsaturated aldehyde via an oxazolidine to prepare C-3-substituted tetrahydroisoquinoline is disclosed. The C-3 stereogenic center is subsequently exploited to create the C-1 stereocenter by coordination of the nucleophilic reagent to the oxygen atom of oxazolidine. Both cis- and trans-1,3-disubstituted tetrahydroisoquinolines can be readily prepared. In addition, when a cationic rhodium complex was used, intramolecular hydroamination was effected, thus avoiding mercury(II) salts and demercuration. The reaction is general and works well using aliphatic and aromatic aldehydes. PMID- 27404667 TI - Determinants of Physical Activity in Patients with Chronic Obstructive Pulmonary Disease: A 5-Year Prospective Follow-Up Study. AB - BACKGROUND: Although many studies examined determinants of physical activity in patients with chronic obstructive pulmonary disease (COPD), most were cross sectional and focused on single determinants only. OBJECTIVES: The aim of this study was to determine how COPD patients' physical activity changes over time and to identify the determinants of physical activity using multivariable and longitudinal methods. METHODS: In a prospective cohort study, 409 primary care patients with COPD in the Netherlands and Switzerland were followed for up to 5 years. Physical activity was assessed at baseline and every 6 months using the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire (LAPAQ) adapted to a 0- to 23-point scale. We studied the associations between determinants at baseline and patients' long-term physical activity levels using linear mixed models. RESULTS: Unadjusted analysis showed an overall gradual decline in physical activity (0.22 points of the LAPAQ scale every 6 months, 95% CI: 0.17-0.28; p < 0.001). In multivariable analyses, baseline determinants that were independently associated (p <= 0.05) with lower long-term physical activity levels included (starting from coefficients with the smallest p value) lower exercise capacity, older age, working, more smoking pack-years, more fatigued, male sex, lower educational levels, previously not in fitness programs, more depressed, lower lung function, lower overall health status, and more prescription drug use. CONCLUSIONS: We found that physical activity of COPD patients may decline more than reported in the healthy elderly. Longitudinal analysis identified independent determinants of physical activity, which allows the identification of patients having low physical activity levels and who may benefit from physical activity interventions. PMID- 27404669 TI - Correction: Body Size Regression Formulae, Proximate Composition and Energy Density of Eastern Bering Sea Mesopelagic Fish and Squid. AB - [This corrects the article DOI: 10.1371/journal.pone.0132289.]. PMID- 27404668 TI - Results of a 2-arm, phase 2 clinical trial using post-transplantation cyclophosphamide for the prevention of graft-versus-host disease in haploidentical donor and mismatched unrelated donor hematopoietic stem cell transplantation. AB - BACKGROUND: High-dose, post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD) has improved outcomes in haploidentical (HAPLO) stem cell transplantation (SCT). However, it remains unclear whether this strategy is effective in SCT from 1-antigen human leukocyte antigen (HLA) mismatched unrelated donors (9/10 MUD) and how the outcomes of these patients compare with those of haploidentical transplantation recipients. METHODS: A parallel, 2-arm, nonrandomized phase 2 clinical trial was conducted of melphalan based reduced-intensity conditioning with PTCy, tacrolimus, and mycophenolate mofetil to prevent GVHD in patients with high-risk hematologic malignancies who underwent HAPLO (n = 60) or 9/10 MUD (n = 46) SCT. RESULTS: The 1-year overall and progression-free survival rates were 70% and 60%, respectively, in the HAPLO arm and 60% and 47%, respectively, in the 9/10 MUD arm. The day +100 cumulative incidence of grade II to IV acute GVHD and grade III to IV acute GVHD was 28% and 3%, respectively, in the HAPLO arm and 33% and 13%, respectively, in the 9/10 MUD arm. The 2-year cumulative incidence of chronic GVHD was 24% in the HAPLO arm and 19% in the 9/10 MUD arm. The 1-year cumulative incidence of nonrelapse mortality was 21% in the HAPLO arm and 31% in the 9/10 MUD arm, and the 1-year relapse rate was 19% in the HAPLO arm and 25% in the 9/10 MUD arm. CONCLUSIONS: Although this was a nonrandomized study and could not serve as a direct comparison between the 2 groups, the authors conclude that PTCy-based GVHD prophylaxis is effective for both HAPLO and 9/10 MUD SCTs. Prospective randomized trials will be required to compare the efficacies of alternative donor options for patients lacking HLA matched donors. Cancer 2016;122:3316-3326. (c) 2016 American Cancer Society. PMID- 27404670 TI - Overall uncertainty measurement for near infrared analysis of cryptotanshinone in tanshinone extract. AB - This study presented a new strategy of overall uncertainty measurement for near infrared (NIR) quantitative analysis of cryptotanshinone in tanshinone extract powders. The overall uncertainty of NIR analysis from validation data of precision, trueness and robustness study was fully investigated and discussed. Quality by design (QbD) elements, such as risk assessment and design of experiment (DOE) were utilized to organize the validation data. An "I*J*K" (series I, the number of repetitions J and level of concentrations K) full factorial design was used to calculate uncertainty from the precision and trueness data. And a 2(7-4) Plackett-Burmann matrix with four different influence factors resulted from the failure mode and effect analysis (FMEA) analysis was adapted for the robustness study. The overall uncertainty profile was introduced as a graphical decision making tool to evaluate the validity of NIR method over the predefined concentration range. In comparison with the T. Saffaj's method (Analyst, 2013, 138, 4677.) for overall uncertainty assessment, the proposed approach gave almost the same results, demonstrating that the proposed method was reasonable and valid. Moreover, the proposed method can help identify critical factors that influence the NIR prediction performance, which could be used for further optimization of the NIR analytical procedures in routine use. PMID- 27404671 TI - A literature review to evaluate the clinical and economic value of olmesartan for the treatment of hypertensive patients. AB - The objective of the present study was to systematically review the clinical and economic outcomes of olmesartan as monotherapy or in combination with other antihypertensive agents in the treatment of hypertension. A literature search was performed using PubMed and the Cochrane library until December 2015, with no limit on publication date. Eligible studies were selected using predetermined inclusion and exclusion criteria, limiting articles to those published in the English language. Background information of the study, participants' characteristics and study outcomes were collected. Meta-analysis of data was not performed. Fifty-five studies were included, of which fifty investigated the clinical efficacy of olmesartan and five the cost-effectiveness of olmesartan. In general results from clinical trials evaluating the efficacy of olmesartan as monotherapy and as combination therapy demonstrated that olmesartan provided better antihypertensive blood pressure-lowering efficacy and was generally well tolerated compared with other antihypertensive agents. Results from economic evaluations indicated that olmesartan may be more cost-effective than other ARBs such as losartan, valsartan, irbesartan and candesartan, having the potential of decreasing the overall medical costs of care for patients with hypertension. Evidence from the present systematic review confirms the antihypertensive efficacy and good safety profile of olmesartan both as monotherapy and as combination therapy. Olmesartan was also found to be cost-effective compared with other ARBs, though this area has yet relatively poor evidence and needs to further be explored. PMID- 27404672 TI - Prognostic value of aortic regurgitation after TAVI in patients with chronic kidney disease. AB - BACKGROUND: Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic valve stenosis results in major haemodynamic changes. Influence of post-implant AR and aortic valve calcification on outcome in patients with chronic kidney disease (CKD) is unclear. METHODS: Short-term outcome was defined as a combined 30-day endpoint, long-term outcome as survival. Post-implant AR was classified as none/mild or moderate/severe using transthoracic echocardiography. Aortic valve calcification was calculated by computed tomography. Logistic regression analyses were performed in patients with none/mild (estimated glomerular filtration rate [eGFR]>=30ml/min/1.73m(2)) and advanced (eGFR<30ml/min/1.73m(2)) CKD to evaluate predictors of outcome and post implant AR. RESULTS: TAVI was performed in 546 consecutive patients. Moderate/severe post-implant AR was the only independent predictor of the 30-day endpoint in patients with advanced (OR 7.091, 95% CI 1.144-43.962, p=0.035), but not in patients with none/mild CKD. Similarly, moderate/severe AR predicted impaired survival only in patients with advanced CKD (p<0.001). NT-proBNP (OR 1.023 per 500ng/l increase, 95% CI 1.003-1.043; p=0.026) before intervention was the only independent predictor of the 30-day endpoint in patients with none/mild CKD. Aortic valve calcification was comparable in patients with none/mild versus advanced CKD and was an independent predictor of moderate/severe post-implant AR in the overall population as well as in the subgroups with none/mild or advanced CKD. CONCLUSIONS: Moderate/severe AR after TAVI predicts outcome in patients with advanced CKD, but not in patients with none/mild CKD. Aortic valve calcification is an important predictor of post-implant AR independent of kidney function. PMID- 27404673 TI - Prognostic impact of early treatment with tolvaptan in patients with acute heart failure and renal dysfunction. AB - BACKGROUND: Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated. METHODS: Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. RESULTS: During follow-up (636days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P=0.197) or all-cause death (Log-rank: P=0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (>20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30-0.91, P=0.021) with a significant interaction (P value for interaction=0.045). Likewise, in patients whose eGFR was 30mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P=0.017) with a significant interaction (P value for interaction=0.015). CONCLUSION: Short-term use of tolvaptan in acute phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan. PMID- 27404674 TI - Head-up tilt test results in child twins with nervous mediated syncope. AB - OBJECTIVE: To investigate the familial genetic characteristics of syncope in children. METHODS: A detailed medical history was taken from four twin pairs of children complaining of dizziness, headache, chest tightness, chest pain, prodromal symptoms of syncope or syncope, meanwhile, these patients were given routine physical examination, 12-lead ECG, echocardiography, Holter ECG, EEG, MRI of the head and other tests to exclude cardio-cerebrovascular and pulmonary diseases, with those with unknown origin for syncope undergoing head-up tilt test (HUTT) and inquiry of detailed family history. RESULTS: The four pairs of twins with syncope beginning at 7-12years and induced mostly by standing position (4/5), and positive family history was noted in two pairs. Vasovagal syncope (VVS)-vasoinhibitory response pattern was predominant in HUTT (4/5). The results and the response pattern in HUTT might diversify between two members within same twin pair: one appeared as vasoinhibitory response pattern and one postural orthostatic tachycardia syndrome (POTS) pattern in the first pair, one vasoinhibitory response pattern and one negative response pattern in the second pair, vasoinhibitory response pattern in the third pair and negative response pattern in the fourth pair. CONCLUSIONS: The hereditary factors may play a more important role in younger children with syncope. Environment and psychological factors may induced syncope attack. The results and the response pattern in HUTT are diversified and which might different between two members within twin pair. PMID- 27404675 TI - Addition of beta-blockers to digoxin is associated with improved 1- and 10-year survival of patients hospitalized due to decompensated heart failure. AB - BACKGROUND: Many of the studies associating digoxin use with increased mortality were conducted before beta-blockers became a standard therapy for heart failure (HF) patients. Our goal was to determine the effect of beta-blockers on the prognosis of patients hospitalized for decompensated HF who receive digoxin therapy at discharge. METHODS: We analyzed 2402 patients admitted with a primary diagnosis of decompensated HF during the prospective National Heart Failure Survey in Israel. Multivariate modeling was used to determine the effect of beta blockers and digoxin on 1- and 10-year survival. RESULTS: Patients discharged on digoxin and beta-blockers (DIG+/BB+) had a lower 1-year mortality rate than those discharged on digoxin alone (DIG+/BB-), (31% vs. 44%; p<0.001). Digoxin administration was associated with an increase in adjusted 1-year (Hazard ratio [HR] 1.28; 95% confidence interval (CI) 1.08-1.50) and 10-year mortality risk (HR 1.27; CI 1.16-1.42), whereas beta-blocker administration was associated with a decrease in adjusted 1-year (HR 0.76; CI 0.68-0.87) and 10-year mortality risk (HR 0.83; CI 0.77-0.89; all p<0.001). In comparison to a DIG-/BB+ group serving as a reference, multivariate adjusted HR for DIG+/BB+ and DIG+/BB- groups were 1.36 (CI 1.03-1.91; p<0.001) and 2.01 (CI 1.59-2.85; p<0.001) at 1-year, and 1.04 (CI 0.84-1.28; p>0.1) and 1.37 (CI 1.17-1.76; p<0.001) at 10years. CONCLUSION: In patients hospitalized with decompensated HF, digoxin administration at discharge is associated with increased 1- and 10-year mortality risk. However, the simultaneous use of beta-blockers and digoxin is associated with lower 1- and 10 year mortality risk when compared to use of digoxin alone. PMID- 27404676 TI - The causes, treatment, and outcome of pulmonary hypertension in Africa: Insights from the Pan African Pulmonary Hypertension Cohort (PAPUCO) Registry. AB - BACKGROUND: Epidemiology, aetiology, management and outcome data for various forms of pulmonary hypertension (PH) in Africa are scarce. METHODS: A prospective, multinational cohort registry of 220 consecutive patients (97% of African descent) from 9 specialist centres in 4 African countries. The antecedents, characteristics and management of newly diagnosed PH plus 6-month survival were studied. RESULTS: There were 209 adults (median age 48years [IQR 35, 64]) and 11 children (age range 1 to 17years). Most adults had advanced disease - 66% WHO Functional Class III-IV, median 6-minute walk test distance of 252m (IQR 120, 350) and median right ventricular systolic pressure 58mmHg (IQR 49, 74). Adults comprised 16% pulmonary arterial hypertension, 69% PH due to left heart disease, 11% PH due to lung disease and/or hypoxia, 2% chronic thromboembolic pulmonary hypertension, and 2% PH with unclear multifactorial mechanism. At 6-months, 21% of adults with follow-up data had died. On an adjusted basis (independent of sub-groups) mortality was associated with increasing functional impairment (p=0.021 overall - WHO Class IV versus I, OR 1.68 [95% CI 0.13, 4.36]) and presence of combined right atrial and ventricular hypertrophy (46% - OR 2.88, 95% CI 1.45, 5.72). Children commonly presented with dyspnoea, fatigue, cough, and palpitations with six and three children, respectively diagnosed with concurrent PH associated congenital heart disease and left heart disease. CONCLUSIONS: These data provide new insights into PH from an African perspective, with clear opportunities to improve its prevention, treatment and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02265887). PMID- 27404678 TI - Left ventricular myocardial strain gradient using a novel multi-layer transthoracic echocardiography technique positively correlates with severity of aortic stenosis. PMID- 27404677 TI - Mild cognitive impairment predicts death and readmission within 30days of discharge for heart failure. AB - BACKGROUND: Cognitive impairment is highly prevalent in heart failure (HF), and may be associated with short-term readmission. This study investigated the role of cognition, incremental to other clinical and non-clinical factors, independent of depression and anxiety, in predicting 30-day readmission or death in HF. METHODS: This study followed 565 patients from an Australia-wide HF longitudinal study. Cognitive function (MoCA score) together with standard clinical and non clinical factors, mental health and 2D echocardiograms were collected before hospital discharge. The study outcomes were death and readmission within 30days of discharge. Logistic regression, Harrell's C-statistic, integrated discrimination improvement (IDI) and net reclassification index were used for analysis. RESULTS: Among 565 patients, 255 (45%) had at least mild cognitive impairment (MoCA<=22). Death (n=43, 8%) and readmission (n=122, 21%) within 30days of discharge were more likely to occur among patients with mild cognitive impairment (OR=2.00, p=0.001). MoCA score was also negatively associated with 30 day readmission or death (OR=0.91, p<0.001) independent of other risk factors. Adding MoCA score to an existing prediction model of 30-day readmission significantly improved discrimination (C-statistic=0.715 vs. 0.617, IDI estimate 0.077, p<0.001). From prediction models developed from our study, adding MoCA score (C-statistic=0.83) provided incremental value to that of standard clinical and non-clinical factors (C-statistic=0.76) and echocardiogram parameters (C statistic=0.81) in predicting 30-day readmission or death. Reclassification analysis suggests that addition of MoCA score improved classification for a net of 12% of patients with 30-day readmission or death and of 6% of patients without (p=0.002). CONCLUSIONS: Mild cognitive impairment predicts short-term outcomes in HF, independent of clinical and non-clinical factors. PMID- 27404679 TI - Amelioration of right ventricular function after hybrid therapy with riociguat and balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. PMID- 27404680 TI - Sport, health and sudden death. PMID- 27404681 TI - Heat, heat waves, and out-of-hospital cardiac arrest. AB - OBJECTIVE: Cardiac arrest is one of the common presentations of cardiovascular disorders and a leading cause of death. There are limited data on the relationship between out-of-hospital cardiac arrest (OHCA) and ambient temperatures, specifically extreme heat. This study investigated how heat and heat waves affect the occurrence of OHCA. METHODS: Seven major cities in Korea with more than 1 million residents were included in this study. A heat wave was defined as a daily mean temperature above the 98th percentile of the yearly distribution for at least two consecutive days. RESULTS: A total of 50,318 OHCAs of presumed cardiac origin were identified from the nationwide emergency medical service database between 2006 and 2013. Ambient temperature and OHCA had a J shaped relationship with a trough at 28 degrees C. Heat waves were shown to be associated with a 14-% increase in the risk of OHCA. Adverse effects were apparent from the beginning of each heat wave period and slightly increased during its continuation. Excess OHCA events during heat waves occurred between 3PM and 5PM. Subgroup analysis showed that those 65years or older were significantly more susceptible to heat waves. CONCLUSIONS: Ambient temperature and OHCA had a J-shaped relationship. The risk of OHCA was significantly increased with heat waves. Excess OHCA events primarily occurred during the afternoon when the temperature was high. We found that the elderly were more susceptible to the deleterious effects of heat waves. PMID- 27404682 TI - High serum osmolarity at admission determines a worse outcome in patients with heart failure: Is a new target emerging? AB - AIMS: The osmolarity of human serum is restricted to a tightly regulated range, and any deviation has clinical implications. Our aim in this study was to establish whether differences in serum osmolarity in heart failure (HF) patients are related with a worse outcome. METHODS: We evaluated the prognostic value of serum osmolarity in patients with HF from the Spanish National Registry on Heart Failure (RICA), a multicenter, prospective registry that enrolls patients admitted for decompensated HF and follows them for 1year. Patients were divided into quartiles according to osmolarity levels. Primary endpoint was the combination of all-cause mortality and hospital readmissions for HF. RESULTS: A total of 2568 patients (47.46% men) were included. Patients with higher osmolarity were older, presented more comorbidities (especially diabetes mellitus and chronic kidney disease), and consequently had higher levels of glucose, urea, creatinine and potassium. During the 1-year follow-up, mortality among the quartiles was 18% (Q1), 18% (Q2), 23% (Q3) and 28% (Q4), p<0.001. After adjusting for baseline characteristics, high serum osmolarity was significantly associated with all-cause mortality (RR 1.02, 95% CI 1.01-1.03, p<0.001). We also found a significant increase in the combined endpoint of mortality and readmission among quartiles with higher osmolarity (p<0.001). Diabetes, eGFR, Barthel index, systolic blood pressure, body mass index, hemoglobin, NYHA class and beta blocking agents were also independently associated with the primary endpoint. CONCLUSIONS: In patients admitted for decompensated HF, high serum osmolarity predicts a worse outcome, and is associated with a higher comorbidity burden, supporting its use as a candidate prognostic target in HF. PMID- 27404683 TI - Neointimal coverage of overlapping everolimus-eluting bioresorbable scaffolds: An optical coherence tomography study in native coronary arteries. PMID- 27404684 TI - Depression in heart failure: Can PHQ-9 help? AB - BACKGROUND: The Patient Health Questionnaire 9 (PHQ-9) is an effective tool for identification and grading of depression symptoms. Data on PHQ-9 utility for patients with heart failure (HF) are limited. METHODS: We evaluated the severity of depression by PHQ-9 at baseline and its association with health care resource utilization (HCRU) rates and quality of life (QoL) in 308 outpatients enrolled in a prospective HF cohort study. Depression symptoms were stratified according to PHQ-9 score as minimal (0-4), mild (5-9), or moderate-to-severe (10-27). RESULTS: Mean age of patients was 57+/-11years; 65% were men; 50% were white and 47% black; ejection fraction was 30+/-15%. Over 24+/-12months (total: 625person years), there were 41 (13.3%) major clinical events (34 deaths, 5 transplants, 2 ventricular assist device implantations), 633 all-cause admissions (249 [39.3%] for HF), and 362 emergency department (ED) visits. Moderate-to-severe depressive symptoms were associated with 70% more all-cause admissions compared to patients without depressive symptoms and 2.5 times more HF-related admissions. However, less than 50% of patients with moderate-to-severe symptoms were on antidepressants. In adjusted analyses, even mild depressive symptoms were associated with 57% more all-cause admissions compared to patients without depressive symptoms and more than 2-fold higher rate of HF-related admissions. Depressive symptoms were not associated with ED visits. Increasing PHQ-9 score was associated with progressively worse QoL. PHQ-9 was not associated with major clinical events. CONCLUSIONS: PHQ-9 effectively identifies HF patients at risk for increased HCRU and lower QoL. Interventions to reduce depression symptoms may help improve HF outcomes. PMID- 27404685 TI - The efficacy of N-acetylcysteine plus sodium bicarbonate in the prevention of contrast-induced nephropathy after cardiac catheterization and percutaneous coronary intervention: A meta-analysis of randomized controlled trials. AB - BACKGROUND: The efficacy of combining use of N-acetylcysteine (NAC) and sodium bicarbonate (SOB) in the prevention of contrast-induced nephropathy (CIN) after cardiac catheterization and percutaneous coronary intervention (PCI) is unclear. METHODS: All relevant studies that compared the effect of combining the use of NAC and SOB with individual use on CIN in patients undergoing cardiac catheterization and PCI were identified by searching the databases including Pubmed, Embase, Cochrane Library, and Web of Science without time and language limitation. Only randomized controlled trials (RCTs) with full-text published were considered. RESULTS: Sixteen RCTs involving 4432 cases were included into this meta-analysis. The results showed there were no additional benefit in reduction of CIN in COM group (COM versus NAC: RR 0.85, 95% CI 0.70-1.03, P=0.103; COM versus SOB: RR 0.91, 95% CI 0.71-1.16, P=0.449), even in patients with diabetes mellitus (COM versus NAC: RR 1.11, 95% CI 0.71-1.75, P=0.646; COM versus SOB: RR 1.06, 95% CI 0.45-2.47, P=0.893), undergoing PCI procedure (COM versus NAC: RR0.76, 95% CI 0.39-1.47, P=0.411; COM versus SOB: RR0.96, 95% CI 0.65-1.40, P=0.814), or with baseline renal dysfunction (COM versus NAC: RR 0.89, 95% CI 0.70-1.14, P=0.366; COM versus SOB: RR 0.95, 95% CI 0.67-1.36, P=0.788). CONCLUSIONS: The present study demonstrated combining use of NAC and SOB was not significantly superior to individual use method in the prevention of CIN after cardiac catheterization and PCI. PMID- 27404686 TI - Prevalence of rheumatic heart disease among school children in Ethiopia: A multisite echocardiography-based screening. AB - BACKGROUND: Auscultation-based surveys in Ethiopia conducted in the late 1990's reported a rural prevalence of 4.6/1000 and an urban prevalence of 6.4/1000 of rheumatic heart disease (RHD). With echo-based screening, we aimed to estimate the national prevalence of RHD in school children by taking school-based samples from six regions across the country using the 2012 World Heart Federation echocardiographic criteria. PATIENTS AND METHODS: We conducted a cross-sectional echocardiographic screening of RHD in school children aged 6-18years from 28 randomly selected primary and secondary schools found in six different geographic regions of Ethiopia. We used the standardized WHF echocardiographic criteria. RESULTS: A total of 3238 children (48.5% females) were screened. The mean age was 13.2+/-3.2years. Of these, 44 patients (1.4%) met the WHF criteria for definite RHD, while 15 (0.5%) met the criteria for borderline disease, yielding a prevalence of 19 [13.9-23.4, 95% CI] cases per 1000 school children between the ages of 6-18years. The majority of those who tested positive were girls (26/44). The prevalence was lowest in children aged 6-9years and otherwise uniformly distributed across ages 10-18years. Definite RHD involved the mitral valve in 42 subjects, 39 of whom had mitral regurgitation and 3 with mitral stenosis. The aortic valve was affected in 6 children. The ratio of definite to borderline cases was 2.9. CONCLUSION: This study demonstrated a consistent pattern of high prevalence of asymptomatic RHD with definite disease predominating over borderline involvement across six regions of Ethiopia. PMID- 27404688 TI - Impact of right ventricular size and function on survival following transcatheter aortic valve replacement. AB - BACKGROUND: The impact of pre-procedural RV size and function on outcomes following transcatheter aortic valve replacement (TAVR) is not well established. The aim of this study was to investigate the role of right ventricular size and function on outcomes following TAVR. METHODS AND RESULTS: Between November 2008 and June 2013, 268 consecutive patients (age 80.5+/-7.9years, aortic valve area 0.79+/-0.16cm(2)) with symptomatic severe aortic stenosis (AS) undergoing TAVR at Mayo Clinic were included. Transthoracic echocardiographic quantitative and semiquantitative assessment of RV chamber size and systolic function was performed and included tricuspid annular plane systolic excursion (TAPSE), RV systolic excursion velocity (S'), fractional area change (FAC), RV index of myocardial performance (RIMP). The primary endpoint of all-cause mortality after TAVR was measured and observed in 65 patients (median follow up duration: 412days). Univariate analysis identified semiquantitative RV dilatation (p<0.001) and systolic dysfunction (p=0.013), RV basal dimension (p=0.003) and RV outflow proximal dimension (p=0.031) to be of prognostic significance. After multivariate adjustment, patients with semiquantitative RV dilatation (HR 2.61, 95% CI 1.45 4.65, p=0.002) and larger RV basal dimension (HR 1.07, 95% CI per mm 1.02-1.11, p=0.007) had significantly worse survival even after adjusting for age, sex, Society of Thoracic Surgeons (STS) risk score, left ventricular ejection fraction, tricuspid regurgitation, pulmonary artery systolic pressure, and atrial fibrillation. CONCLUSION: RV dilatation is an important determinant of postoperative outcomes in patients undergoing TAVR. PMID- 27404687 TI - Prevalence and outcomes of trans-radial access for percutaneous coronary intervention in contemporary practise. AB - BACKGROUND: Trans-radial access for percutaneous coronary intervention (PCI) has been associated with lower vascular complication rates and improved outcomes. We assessed the current uptake of trans-radial PCI in Victoria, Australia, and evaluated if patients were selected according to baseline bleeding risk in contemporary clinical practise, and compared selected clinical outcomes. METHODS: PCI data of all patients between 1st January 2013 and 31st December 2014 were analysed using The Victorian Cardiac Outcomes Registry (VCOR). Propensity-matched analysis was performed to compare the clinical outcomes. RESULTS: 11,711 procedures were analysed. The femoral route was the predominant access site (66%). Patients undergoing trans-radial access PCI were younger (63.9+/-11.6 vs. 67.2+/-11.8; p<0.001), had a higher BMI (28.9+/-5.5 vs. 28.5+/-5.2; p<0.001), more likely to be male (80.0 vs. 74.9%;p<0.001), less likely to have presented with cardiogenic shock (0.9 vs. 2.8%; p<0.001) or have the following comorbidities: diabetes (19.8 vs. 23.1%; p<0.001), peripheral vascular disease (2.9 vs. 4.3%; p=0.005) or renal impairment (13.6 vs. 22.1%; p<0.001). The radial group had less bleeding events (3.2 vs. 4.6%; p<0.001) and shorter hospital length of stay (3.1+/-4.7 vs. 3.3+/-3.9; p=0.006). There was no significant difference in mortality (1.0 vs. 1.4%; p=0.095). CONCLUSIONS: Trans-femoral approach remains the dominant access site for PCI in Victoria. The choice of route does not appear to be selected by consideration of bleeding risk. The radial route is associated with improved clinical outcomes of reduced bleeding and length of stay consistent with previous findings, and this supports the efficacy and safety of trans-radial PCI in real-world clinical practise. PMID- 27404689 TI - Echocardiography and NAFLD (non-alcoholic fatty liver disease). AB - Non-alcoholic-fatty-liver-disease (NAFLD) is associated with atherosclerosis, increased cardiovascular risks and mortality. We investigated if, independently of insulin resistance, diet, physical activity and obesity, fatty liver involvement has any relationship with echocardiographic measurements in NAFLD. PATIENTS AND METHODS: 660 NAFLD and 791 non-NAFLD subjects, referred to the same out-patients medical unit for lifestyle-nutritional prescription, were studied. Congestive heart failure, myocardial infarction, malignancies, diabetes mellitus, extreme obesity, underweight-bad-nourished subjects and renal insufficiency were exclusion criteria. Liver steatosis was assessed by Ultrasound-Bright-Liver-Score (BLS), left ventricular ejection fraction (LVEF), trans-mitral E/A doppler ratio (diastolic relaxation) and left ventricular myocardial mass (LVMM/m(2)) by echocardiography. Doppler Renal artery Resistive Index (RRI), insulin resistance (HOMA) and lifestyle profile were also included in the clinical assessment. RESULTS: LVMM/m(2) is significantly greater in NAFLD, 101.62+/-34.48 vs. 88.22+/ 25.61, p<0.0001 both in men and in women. Ejection fraction is slightly smaller only in men with NAFLD; no significant difference was observed for the E/A ratio. BMI (30.42+/-5.49 vs. 24.87+/-3.81; p<0.0001) and HOMA (2.90+/-1.70 vs. 1.85+/ 1.25; p: 0.0001) were significantly greater in NAFLD patients. By Multiple-Linear Regression, NAFLD and unhealthy dietary profile are associated also in lean non diabetic subjects with lower systolic function, independently of BMI, dietary profile, physical activity, RRI and insulin resistance. CONCLUSION: NAFLD may be a meaningful early clue suggestive of diminishing heart function, with similar determining factors. NAFLD is amenable to management and improvement by lifestyle change counseling, addressing a dual target: reducing fatty liver, which is easily monitored by ultrasound, and, independently, maintaining a normal heart function. PMID- 27404690 TI - Catheter ablation of premature ventricular contractions arising from left anterior fascicle guided by an earliest presystolic Purkinje potential. PMID- 27404691 TI - Updates on publication trends in Takotsubo syndrome. PMID- 27404692 TI - Strong diurnal rhythm of troponin T, but not troponin I, in a patient with renal dysfunction. PMID- 27404693 TI - Deceleration capacity: A novel predictor for total mortality in patients with non ischemic dilated cardiomyopathy. AB - OBJECTIVES: We hypothesized that deceleration capacity (DC), a novel marker of cardiac autonomic modulation, is an independent predictor for mortality in patients with non-ischemic dilated cardiomyopathy (NICM). BACKGROUND: NICM is associated with a high risk for sudden cardiac death (SCD). However there are no clinically established parameters available for risk stratification beyond LVEF. DC has been previously shown to be a strong independent predictor for total mortality in patients after myocardial infarction. METHODS: Holter-ECG recordings of 201 patients NICM (83.1% male, mean age: 61.4years, mean LVEF: 33.3%) were analyzed by the method of phase-rectified-signal-averaging (PRSA) to obtain DC. RESULTS: During a minimum follow-up of 40month 59 patients died. Kaplan Meyer Analysis showed a significantly higher mortality in patients with a DC below 4.5ms (log rank p=0.012) irrespective to the presence of atrial fibrillation. CONCLUSIONS: Impaired DC is a powerful independent predictor for mortality in patients with NICM. PMID- 27404694 TI - Validation of the good outcome following attempted resuscitation score on in hospital cardiac arrest in southern Sweden. AB - BACKGROUND: There is a great need for a simple and clinically useful instrument to help physicians estimate the probability of survival to discharge with a good neurological outcome (cerebral performance category, CPC=1) in cases of in hospital cardiac arrest (IHCA). Our aim was to validate the "Good Outcome Following Attempted Resuscitation" (GO-FAR) score in a different country with different demographics than previously investigated. METHODS: A retrospective observational study including all cases of IHCA who were part of a cardiac arrest registry at Skane University Hospital in Sweden 2007-2010. RESULTS: Two-hundred eighty-seven patients suffered IHCA during the period. A majority were male and mean age was 70years. Overall survival to discharge independent of neurological function was 20.2%; 78% of the survivors had CPC=1 and survival to discharge with CPC=1 was 15.7%. The area under the receiver operating characteristics curve for the GO-FAR score was 0.85 (CI=0.78-0.91, p<0.001), consistent with very good discrimination. Patients in the group with low or very low probability of survival had a likelihood of 2.8% (95% CI 0.0-6.7), whereas the groups with average and above average probabilities had likelihoods of 8.2% (3.7-13) and 46% (34-58), respectively, for good neurological outcome. This compares with likelihoods of 1.6%, 9.2% and 27.8% in the original study. CONCLUSION: The GO-FAR score accurately predicted the probability of survival to discharge with CPC=1, even when applied to a different population in another country. PMID- 27404695 TI - Serum pentraxin 3 levels are negatively associated with carotid intima media thickness in non-obese rheumatoid arthritis patients. AB - BACKGROUND: Pentraxin-3 (PTX3) is a long pentraxin that is supposed to participate in the inflammatory process and in atherosclerosis. AIM: To study PTX3 serum levels in rheumatoid arthritis (RA) patients to know if its serum levels may reflect disease activity and/or subclinical atherosclerosis. METHODS: PTX3 and carotid intima media thickness (IMT) were studied in 85 RA patients (83.5% females, median age of 59years old, median disease duration of 13years) along with its demographic, clinical, serological and lipid profile. For comparison PTX3 was measured in 85 healthy volunteers. RESULTS: PTX3 levels in RA patients were similar to controls (p=0.21) and did not correlate with inflammatory activity measured by ESR (p=0.39) CRP (p=0.18) and DAS28 (p=0.67). Serum PTX3 levels were higher in nonobese RA patients than in obese (BMI vs PTX3 with rho=-0.27; 95%IC=-0.46 to -0.06; p=0.009). In non-obese patients, PTX3 correlated negatively with carotid IMT (rho=-0.40; 95%IC=-0.66 to -0.06; p=0.01) but not in the obese ones (p=0.26). In the obese RA patients there was a negative correlation between PTX3 levels and LDL/HDL ratio (Rho=-0.29; 95%IC=-0.53-0.01; p=0.03). CONCLUSIONS: PTX3 levels do not reflect inflammatory process in RA. However, it exerts a protective role in the process of atherogenesis in non-obese RA patients. PMID- 27404696 TI - Long-term administration of tolvaptan increases myocardial remodeling and mortality via exacerbation of congestion in mice heart failure model after myocardial infarction. AB - BACKGROUND: In contrast to loop diuretics, tolvaptan does not cause neurohormonal activation in several animal heart failure models. However, it remains unknown whether chronic vasopressin type 2 receptor blockade exerts beneficial effects on mortality in murine heart failure after myocardial infarction (MI). In an experimental heart failure model, we tested the hypothesis that tolvaptan reduces myocardial remodeling and mortality. METHODS AND RESULTS: MI was induced in 9 week-old male C57Bl6/J by the left coronary artery ligation. In study 1, animals were randomly assigned to treatment with placebo or tolvaptan starting 14days post-MI. In study 2, animals were randomized to tolvaptan or furosemide+tolvaptan starting 14days post-MI. Interestingly, results showed lower survival rate in tolvaptan group compared to placebo. Tolvaptan group had higher serum osmolality, heavier body weight, more severe myocardial remodeling, and lung congestion at day 28 of drug administration compared to placebo. In study 2, addition of furosemide significantly reduced mortality rate seen with tolvaptan, and presented with decreased osmolality, myocardial remodeling, and lung congestion compared to tolvaptan-treated mice. Increase in proximal tubular expression of aquaporin 1, Angiotensin II, and vasopressin seen with tolvaptan treatments were normalized to basal levels, similar to levels in placebo-treated mice. CONCLUSIONS: Contrary to our hypothesis, tolvaptan was associated with increased mortality in murine heart failure after MI. This increase in lung congestion, myocardial remodeling, could be prevented by co-administration of furosemide, which resulted in normalized serum osmolality, neurohormonal activation, and renal aquaporin 1 expression, and hence decreased mortality post-MI. PMID- 27404697 TI - Left ventricular size as a predictor of outcome in patients of non-ischemic dilated cardiomyopathy with severe left ventricular systolic dysfunction. AB - BACKGROUND: Limited data is available regarding prognosis of patients with severe left ventricular (LV) systolic dysfunction and varying LV dimensions. Purpose of this study was to compare outcomes of patients with non-ischemic dilated cardiomyopathy (DCM) with respect to LV size. METHODS: 145 patients of DCM cohort with LV ejection fraction <35% were divided into 3 groups. Group 1 with normal LV dimensions, group 2 with mild-moderately enlarged left ventricle and group 3 with severely dilated left ventricle. Primary endpoint was composite of all cause mortality and heart failure hospitalizations at end of follow-up. RESULTS: Forty four patients (30.3%) with normal LV diastolic diameter (51.9+/-5.3mm) were included in group 1, 57(39.3%) with mild-moderately enlarged LV (61.4+/-3.7mm) in group 2 and 44(30.3%) with severely enlarged LV (71.3+/-7.4mm) in group 3. Mean follow-up was 42.2+/-31.6months. Primary end point occurred in 4 patients (9.1%) in group 1, 8 patients (14%) in group 2 and 9 patients (20.5%) in group 3, p=0.23 by log-rank test. Hazard ratio for primary endpoint in group 2 as compared to group 1 was 1.71(95% CI, 0.51 to 5.67; p=0.39) and in group 3 as compared to group 1 was 1.61(95% CI, 0.89 to 2.91; p=0.11). Of patients with more than two years of follow-up, 2 of 29 patients(6.9%) died in group 1, 3 of 35 patients(8.6%) in group 2 and 3 of 34 patients(8.8%) died in group 3, p=0.95. CONCLUSIONS: Intermediate term prognosis of patients with severe LVSD and severely dilated left ventricle is good, with outcomes similar to patients with normal or mild-moderately dilated left ventricle. PMID- 27404698 TI - Recall of patients discharged from follow-up after repair of isolated congenital shunt lesions. AB - BACKGROUND: Discharge from follow-up after closure of isolated congenital shunt lesions in childhood was common practice in the past. The aim of the present study was to recall these patients to evaluate their current status. METHODS: Patients included in the database of pediatric and congenital heart disease of our tertiary center with repaired secundum atrial septal defect (ASD) or ventricular septal defect (VSD) before the age of 18years, and discharged from follow-up, were invited for clinical and echocardiographic check-up. RESULTS: Forty-six ASD patients (age 30+/-7years, 37% male) responded. Median age at ASD repair was 6 (IQR 4-8) years. All but one functioned in NYHA class I. Eight (17%) patients reported palpitations. No patient developed pulmonary hypertension (PH). Right ventricular (RV) dilatation was present in 7 (15%). RV fractional area change (FAC) was <35% in 7 (15%), TAPSE <17mm in 12 (26%). Forty-seven VSD patients (age 34 (IQR 29-40) years, 57% male) participated. Median age at VSD repair was 4 (IQR 1-5) years. Six (13%) patients functioned in NYHA class II. Seventeen (36%) patients reported palpitations. Four (9%) patients presented PH. Left ventricular dilatation was present in 4 (9%), RV dilatation in 6 (13%). RV FAC was <35% in 7 (15%), TAPSE <17mm in 17 (36%). Seven (15%) patients had dilated ascending aorta. CONCLUSIONS: Patients with closure of isolated secundum type ASD in childhood do well, but some have persistent RV dilatation and dysfunction. By contrast, more patients after VSD closure were symptomatic and presented with RV dilatation and dysfunction, PH, and a dilated ascending aorta. PMID- 27404699 TI - Beneficial effect of early infusion of landiolol, a very short-acting beta-1 adrenergic receptor blocker, on reperfusion status in acute myocardial infarction. AB - BACKGROUND: An early IV beta blocker during primary percutaneous coronary intervention (PCI) has been shown to reduce infarct size in ST-segment elevation acute myocardial infarction (STEMI), although the underlying mechanism is unknown. The aim of this study was to investigate the efficacy of early infusion of landiolol, the short-acting beta-1 adrenergic receptor blocker, on the reperfusion status in a STEMI. METHODS: We conducted a prospective, single-group trial of landiolol during the primary PCI for a STEMI. Landiolol was started intravenously just before reperfusion. The reperfusion status and outcomes in 55 treated patients were compared with those in 60 historical controls treated without landiolol. The optimal reperfusion was assessed by an ST-segment resolution (STR), coronary flow, and myocardial brush grade (MBG) after reperfusion. RESULTS: Patients in the landiolol group achieved a higher rate of an STR (64% vs. 42%, p=0.023) and MBG 2/3 (64% vs. 45%, p=0.045), whereas coronary flow was comparable between the two groups. A multivariate analysis showed that landiolol use was an independent predictor of an STR (odds ratio 2.99, 95% confidence interval 1.25-7.16, p=0.014). The incidence of non-sustained ventricular tachycardia (27% vs. 50%, p=0.014), hypotension (15% vs. 32%, p=0.046), and progression to Killip class grade III or IV (0% vs. 10%, p=0.028) were lower in the landiolol group. CONCLUSION: Early infusion of landiolol during the primary PCI was associated with optimal reperfusion and a lower incidence of adverse events in comparison with the control group. PMID- 27404700 TI - Elevated copeptin is a prognostic factor for mortality even in patients with renal dysfunction. AB - BACKGROUND: Copeptin has turned out to give valuable prognostic information for future cardiovascular events. However, since its plasma concentration directly depends on renal function, the value of copeptin as a predictor for outcome also in patients with chronic kidney disease (CKD) is unknown. METHODS: In this single center substudy of the German Coronary Artery Disease-REnal Failure (CAD-REF) registry, 301 patients with an angiographically diagnosed stenosis >=50% in at least one major coronary vessel were included. Estimated glomerular filtration rate (eGFR) was determined using the MDRD formula and patients were classified according to their CKD stage. Copeptin concentrations were measured before initial angiography. Follow-up was performed at 180days, study endpoint was all cause mortality. RESULTS: Of the 301 included patients, 35 (11.6%) patients had no CKD, 113 (37.5%) had CKD stage 1 or 2, 117 (38.9%) had CKD stage 3, and 36 (12.0%) had CKD stage 4 or 5. Copeptin was elevated (>=14pmol/L) in 81 (26.9%) patients and normal (<14pmol/L) in 220 (73.1%) patients. Copeptin values significantly increased with decreasing eGFR (p<0.001) and were strongly correlated with creatinine values (r=0.567, p<0.001). During 180days of follow up, 15 patients (5.0%) died, 10 of them with elevated copeptin values. Multivariate Cox regression analysis showed that copeptin was the sole predictor for mortality (HRR 5.317 (95% CI 1.653-17.098), p=0.005), independent of serum creatinine. CONCLUSION: Elevated copeptin can be used as a valuable prognostic factor for intermediate-term mortality in patients with both coronary artery and renal disease. PMID- 27404701 TI - Galen's book on sphygmology. PMID- 27404702 TI - Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction. AB - BACKGROUND: Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. METHODS: Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3beta (GSK3beta) signaling pathway was tested by western blotting. RESULTS: EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3beta signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. CONCLUSION: ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. PMID- 27404703 TI - Left main "Culotte in Culotte" to manage a trapped broken balloon. PMID- 27404704 TI - Pulmonary embolism treatment: Why not a catheter-directed strategy? PMID- 27404705 TI - Optical coherence tomography guidance for percutaneous coronary intervention with bioresorbable scaffolds. AB - BACKGROUND: The effect of optical coherence tomography (OCT) guidance on the implantation strategy during all phases of percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVSs) in a real-world scenario has been poorly investigated. METHODS: Consecutive patients undergoing BVS implantation at our institution were included in this registry. Frequency-domain OCT pullbacks were performed at the operator's discretion during all phases of BVS implantation procedures to optimize preparation of lesions, confirm BVS size, and optimize expansion and apposition of scaffolds. RESULTS: Between September 2012 and July 2015, 203 BVSs were implanted in 101 consecutive patients at our institution (2.01 BVSs/patient). In 66 patients, the procedure was performed under OCT guidance. In the OCT subgroup, 66 (77.6%) of the 85 treated lesions were complex (B2/C AHA/ACC type). Overall, 147 OCT pullbacks were performed and 72/147 (49.0%) pullbacks indicated the need for changing strategy. After angiography-only-guided optimisation of BVS in 27 (31.8%) lesions, an OCT examination prompted performance of a second post-expansion. This resulted in an increase in the minimal scaffold area (5.5 to 6.3mm(2), p=0.004) and a decrease in the incomplete scaffold apposition area (1.1 to 0.6mm(2), p=0.082), with no new stent fractures. When the population was divided according to the time of BVS implantation, an initial learning adaptation became evident, with the number of OCT-guided changes in strategy significantly decreasing between the initial and final time periods (p=0.017). CONCLUSIONS: OCT guidance for BVS implantation significantly affects the procedural strategy, with favourable effects on acute results and the learning curve. PMID- 27404706 TI - Melatonin is associated with reverse remodeling after cardiac resynchronization therapy in patients with heart failure and ventricular dyssynchrony. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment for left ventricular reverse remodeling (LVRR) in patients with congestive heart failure (HF) and ventricular dyssynchrony. Melatonin is a secretory product of the pineal gland with highly beneficial effects from any tissues including the heart. Herein, we investigated whether the response to CRT is associated with levels of melatonin before CRT implantation in patients with HF and ventricular dyssynchrony. METHODS: Diurnal melatonin levels were performed in serum from 93 patients with HF and ventricular dyssynchrony before CRT implantation. Moreover, we calculated the MADIT-CRT score. Evaluation of patients at 1-year follow-up included an echocardiographic study since the patients were categorized as responders if they presented both a reduction in left ventricular end-systolic volume index >10% and an increase in left ventricular ejection fraction >10%. RESULTS: At 1-year, 34 patients (36.5%) were considered responders to CRT according to the predefined criteria. The diurnal melatonin levels were significantly lower in the non-responder group (9.9+/-2.84 vs 14.7+/-2.32pg/mL). After adjustment by multivariate analysis, diurnal serum melatonin levels (P<0.001) and diabetes mellitus (P=0.03) were predictors of LVRR. On Cox regression analysis, diurnal serum melatonin levels (P<0.001) and left atrial volume<40mL/m(2) (P=0.04) remained independent predictors of the adverse clinical events. The area under of curve for the prediction LVRR of melatonin (0.91, 95%CI 0.85-0.97; P<0.001) was significantly higher compared to MADIT-CRT score (0.69, 95%CI 0.58-0.80; P=0.002). CONCLUSION: Diurnal levels of melatonin before CRT implantation are associated with LVRR at 12month follow-up. PMID- 27404708 TI - Cardiovascular risk and treatment for adults with intellectual or developmental disabilities. AB - BACKGROUND: People with intellectual/developmental disabilities (IDDs) face the development of cardiovascular disease (CVD) similar to the general population. The purpose of this study was to describe and compare the presence of CVD risk factors, the atherosclerotic cardiovascular (ASCVD) risk score, and medication prescribing patterns for medications to treat related risk factors for patients with IDD and those without. METHODS: This was a retrospective study of patients age 18years and older of a health system's primary care medicine practices. The IDD group had documentation of a diagnosis related to IDD. The comparison group was a random sample of patients from the same practices who had no indication of IDD. Patient characteristics included demographics, smoking status, cholesterol, and blood pressure. The presence of a diagnosis of hypertension, hyperlipidemia, diabetes, coronary artery disease, history of stroke or myocardial infarction, and related medication therapy were documented. The dependent variable was the estimated 10-year primary risk of ASCVD. RESULTS: The IDD group included 78 patients while the GenMed group included 187. There were no significant differences in the prevalence of risk-related diagnoses or in blood pressure and cholesterol between the two groups. The estimated 10-year ASCVD risk was significantly higher in the GenMed group compared to the IDD group (p=0.02). Prescribing was similar between the groups. The regression analysis found that group assignment was not significantly associated with ASCVD risk, while age, gender, and race were. CONCLUSIONS: CV risk and related treatment among patients with IDD was similar to that of the general population. PMID- 27404707 TI - Impact of blood transfusion on in-hospital myocardial infarctions according to patterns of acute coronary syndrome: Insights from the BleeMACS registry. AB - BACKGROUND: Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS). METHODS: Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS). RESULTS: Overall, 13,975 patients were included: mean age was 64.1years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244 7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients. CONCLUSIONS: In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis. PMID- 27404709 TI - Interferon gamma may improve cardiac function in Friedreich's ataxia cardiomyopathy. PMID- 27404710 TI - Bipolar disorder, ischemic stroke, mitral valve vegetation and recurrent venous thrombosis due to antiphospholipid syndrome despite rivaroxaban. PMID- 27404711 TI - Unprotected left main intervention for surgery-ineligible patients with coronary artery disease-Usefulness of micro-CT images for stent. AB - BACKGROUND: Percutaneous coronary intervention (PCI) for unprotected left main truncus (LMT) lesions is controversial. Inoperable status with advanced age, renal dysfunction, frailty, or patient request may require an unprotected left main PCI. PCI for LMT is not recommended in the typical clinical situation; however, when it is the only feasible option, the performance is not bad. We demonstrated the result of a cobalt-chromium everolimus-eluting stent (CoCr-EES) in the LMT stenting and serial changes via micro-computed tomography (MUCT). MUCT is an established imaging technique used for high-resolution, non-destructive assessment of vascular samples. The technique has drawn increasing interest for investigations of atherosclerotic arteries in both humans and animal models. There are no reports regarding the linkage between clinical results and MUCT images. METHODS AND RESULTS: Between January 2009 and December 2014, we recruited 118 consecutive, unprotected LMT stenting cases in our institution. We examined the clinical outcomes and angiographic results with a CoCr-EES compared with a first-generation drug-eluting stent. The primary endpoint of this registry was the rate of one-year major adverse cardiac events (MACE). The one-year MACE rate was 2.54%; this did not include the CoCr-EES. We established LMT bifurcation models (mini-crush and culotte) using a CoCr-EES and obtained MUCT images of the CoCr-EES. The images showed no deformation or strut apposition. CONCLUSION: CoCr EES performed well in LMT in our institution and according to MUCT. MUCT images may be useful for anatomical simulation in stent deployment. PMID- 27404712 TI - Transcatheter aortic valve implantation in patients with a mitral prosthesis; single center experience and review of literature. AB - OBJECTIVES: Following the encouraging results of several registries and trials, transcatheter aortic valve implantation (TAVI) has been recognized as a valid option in patients with severe aortic stenosis deemed at high or prohibitive risk for surgical treatment. Good procedural success and good clinical outcomes have been showed and very limited data exist on TAVI in the setting of a preexisting mitral prosthesis regarding the technique, potential complications, and outcomes. METHODS: Here, we report six cases of transfemoral TAVI with a self-expanding bioprosthesis (CoreValve; Medtronic, Inc) in patients who had previously undergone mitral valve replacement. Preprocedural, intraprocedural ve postprocedural outcome and data were analyzed and a brief literature review is also presented. RESULTS AND CONCLUSION: Our experiences show that transfemoral CoreValve implantation can be performed successfully in patients with mechanical and bioprosthetic mitral valves. PMID- 27404713 TI - Secretome from resident cardiac stromal cells stimulates proliferation, cardiomyogenesis and angiogenesis of progenitor cells. AB - In the heart, tissue-derived signals play a central role on recruiting/activating stem cell sources to induce cardiac lineage specification for maintenance of tissue homeostasis and repair. Cardiac resident stromal cells (CRSCs) may play a pivotal role in cardiac repair throughout their secretome. Here, we performed the characterization of CRSCs and their secretome by analyzing the composition of their culture-derived extracellular matrix (ECM) and conditioned medium (CM) and by investigating their potential effect on adipose-derived stem cell (ADSC) and progenitor cell behavior. We confirmed that CRSCs are a heterogeneous cell population whose secretome is composed by proteins related to cellular growth, immune response and cardiovascular development and function. We also observed that CRSC secretome was unable to change the behavior of ADSCs, except for proliferation. Additionally, CM from CRSCs demonstrated the potential to drive proliferation and cardiac differentiation of H9c2 cells and also the ability to induce angiogenesis in vitro. Our data suggest that the CRSCs can be a source of important modulating signals for cardiac progenitor cell recruitment/activation. PMID- 27404714 TI - Fractional flow reserve: A useful tool for interventionists which should be used with caution! PMID- 27404715 TI - Effects of late exercise on cardiac remodeling and myocardial calcium handling proteins in rats with moderate and large size myocardial infarction. AB - BACKGROUND: Physical exercise attenuates myocardial infarction (MI)-induced cardiac remodeling. However, it is unsettled whether late exercise modulates post infarction cardiac remodeling differentially according to infarct size. We investigated the effects of exercise started at late stage heart failure on cardiac remodeling in rats with moderate and large sized MI. METHODS: Three months after MI, rats were assigned into sedentary and exercise groups. Exercise rats underwent treadmill for three months. After assessing infarct size by histological analysis, rats were subdivided into four groups: moderate MI sedentary (Mod MI-Sed; n=7), Mod MI exercised (Mod MI-Ex; n=7), Large MI-Sed (n=11), and Large MI-Ex (n=10). RESULTS: Before exercise, MI-induced cardiac changes were demonstrated by comparing results to a Sham group; alterations were more intense in rats with large than moderate MI size. Systolic function, evaluated by echocardiogram using the variation in LV fractional area change between after and before exercise, was improved in exercise than sedentary groups. Calsequestrin expression increased in exercised compared to sedentary groups. L-type calcium channel was higher in Mod MI-Ex than Mod MI-Sed. SERCA2a, phospholamban, and Na(+)/Ca(2+) exchanger expression did not differ between groups. CONCLUSION: Late exercise improves systolic function and modulates intracellular calcium signaling proteins in rats with moderate and large MI. PMID- 27404716 TI - Preclinical assessment of a modified Occlutech left atrial appendage closure device in a canine model. AB - BACKGROUND: LAA occlusion has a similar stroke prevention efficacy compared to anticoagulation treatment for non-valvular atrial fibrillation. OBJECTIVE: The objective of this study was to assess the feasibility and safety of a modified Occlutech(r) left atrial appendage (LAA) closure device in a canine model. METHODS: The device was implanted in 10 dogs (33+/-1kg) using fluoroscopy and transesophageal echocardiography (TEE) guidance. The modified Occlutech(r) LAA occlusion device was compared with the current version, the Watchman device, and the Amplazter cardiac plug (ACP). LAA occlusion and anchoring to the LAA were evaluated. All dogs were assessed using angiography, TEE, and a gross anatomy examination. RESULTS: The 10 LAA occlusion devices were to be implanted into 10 dogs (5 modified Occlutech devices, 3 current version of Occlutech devices, 1 Watchman, and 1 ACP). LAA implantation was not performed in one dog due to transeptal puncture failure. The three current version of Occlutech devices were embolized immediately after implantation, so three modified devices of the same size were implanted securely without embolization. The mean implant size was 20.1+/-2.0mm. The devices chosen were a mean of 23.3+/-10.6% larger than the measured landing zone diameters. Post-implant angiography and TEE revealed well positioned devices without pericardial effusion or impingement on surrounding structures. CONCLUSIONS: The results of this acute animal study suggested that a modified Occlutech(r) LAA occlusion device was feasible and had greater anchoring performance in canines. Additional large clinical studies are needed to evaluate safety and efficacy. PMID- 27404717 TI - Structural, Dynamical, and Electronic Properties of Liquid Water: A Hybrid Functional Study. AB - We study structural, dynamical, and electronic properties of liquid water through ab initio molecular dynamics (MD) simulations based on a hybrid functional which includes nonlocal van der Waals (vdW) interactions. The water dimer, the water hexamer, and two phases of ice are studied as benchmark cases. The hydrogen-bond energy depends on the balance between Fock exchange and vdW interactions. Moreover, the energetic competition between extended and compact structural motifs is found to be well described by theory provided vdW interactions are accounted for. Applied to the hydrogen-bond network of liquid water, the dispersion interactions favor more compact structural motifs, bring the density closer to the experimental value, and improve the agreement with experimental observables such as radial distribution functions. The description of the self diffusion coefficient is also found to improve upon the combined consideration of Fock exchange and vdW interactions. The band gap and the band edges are found to agree with experiment within 0.1 eV. PMID- 27404718 TI - Discovering Psychological Principles by Mining Naturally Occurring Data Sets. AB - The very expertise with which psychologists wield their tools for achieving laboratory control may have had the unwelcome effect of blinding psychologists to the possibilities of discovering principles of behavior without conducting experiments. When creatively interrogated, a diverse range of large, real-world data sets provides powerful diagnostic tools for revealing principles of human judgment, perception, categorization, decision-making, language use, inference, problem solving, and representation. Examples of these data sets include patterns of website links, dictionaries, logs of group interactions, collections of images and image tags, text corpora, history of financial transactions, trends in twitter tag usage and propagation, patents, consumer product sales, performance in high-stakes sporting events, dialect maps, and scientific citations. The goal of this issue is to present some exemplary case studies of mining naturally existing data sets to reveal important principles and phenomena in cognitive science, and to discuss some of the underlying issues involved with conducting traditional experiments, analyses of naturally occurring data, computational modeling, and the synthesis of all three methods. PMID- 27404719 TI - GFP to BFP Conversion: A Versatile Assay for the Quantification of CRISPR/Cas9 mediated Genome Editing. PMID- 27404720 TI - Hairpin Ribozyme Genes Curtail Alcohol Drinking: from Rational Design to in vivo Effects in the Rat. AB - Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcohol intake. A stepwise approach was followed to design genes encoding ribozymes targeted to the rat ALDH2 mRNA. In vitro studies of accessibility to oligonucleotides identified suitable target sites in the mRNA, one of which fulfilled hammerhead and hairpin ribozyme requirements (CGGUC). Ribozyme genes delivered in plasmid constructs were tested in rat cells in culture. While the hairpin ribozyme reduced ALDH2 activity 56% by cleavage and blockade (P < 0.0001), the hammerhead ribozyme elicited minor effects by blockade. The hairpin ribozyme was tested in vivo by adenoviral gene delivery to UChB alcohol drinker rats. Ethanol intake was curtailed 47% for 34 days (P < 0.0001), while blood acetaldehyde more than doubled upon ethanol administration and ALDH2 activity dropped 25% in liver homogenates, not affecting other ALDH isoforms. Thus, hairpin ribozymes targeted to 16 nt in the ALDH2 mRNA provide durable and specific effects in vivo, representing an improvement on previous work and encouraging development of gene therapy for alcoholism. PMID- 27404728 TI - Loss of Selenium-Binding Protein 1 Decreases Sensitivity to Clastogens and Intracellular Selenium Content in HeLa Cells. AB - Selenium-binding protein 1 (SBP1) is not a selenoprotein but structurally binds selenium. Loss of SBP1 during carcinogenesis usually predicts poor prognosis. Because genome instability is a hallmark of cancer, we hypothesize that SBP1 sequesters cellular selenium and sensitizes cancer cells to DNA-damaging agents. To test this hypothesis, we knocked down SBP1 expression in HeLa cervical cancer cells by employing a short hairpin RNA (shRNA) approach. Reduced sensitivity to hydrogen peroxide, paraquat and camptothecin, reactive oxygen species content, and intracellular retention of selenium after selenomethionine treatment were observed in SBP1 shRNA HeLa cells. Results from Western analyses showed that treatment of HeLa cells with selenomethionine resulted in increased SBP1 protein expression in a dose-dependent manner. Knockdown of SBP1 rendered HeLa cells increased expression of glutathione peroxidase-1 but not glutathione peroxidase-4 protein levels and accelerated migration from a wound. Altogether, SBP1 retains supplemental selenium and sensitizes HeLa cancer cells to clastogens, suggesting a new cancer treatment strategy by sequestering selenium through SBP1. PMID- 27404729 TI - BLT1 signalling protects the liver against acetaminophen hepatotoxicity by preventing excessive accumulation of hepatic neutrophils. AB - Leukotriene B4 (LTB4) is a potent chemoattractant for neutrophils. Signalling of LTB4 receptor type 1 (BLT1) has pro-inflammatory functions through neutrophil recruitment. In this study, we investigated whether BLT1 signalling plays a role in acetaminophen (APAP)-induced liver injury by affecting inflammatory responses including the accumulation of hepatic neutrophils. BLT1-knockout (BLT1(-/-)) mice and their wild-type (WT) counterparts were subjected to a single APAP overdose (300 mg/kg), and various parameters compared within 24 h after treatment. Compared with WT mice, BLT1(-/-) mice exhibited exacerbation of APAP-induced liver injury as evidenced by enhancement of alanine aminotransferase level, necrotic area, hepatic neutrophil accumulation, and expression of cytokines and chemokines. WT mice co-treated with APAP and ONO-0457, a specific antagonist for BLT1, displayed amplification of the injury, and similar results to those observed in BLT1(-/-) mice. Hepatic neutrophils in BLT1(-/-) mice during APAP hepatotoxicity showed increases in the production of reactive oxygen species and matrix metalloproteinase-9. Administration of isolated BLT1-deficient neutrophils into WT mice aggravated the liver injury elicited by APAP. These results demonstrate that BLT1 signalling dampens the progression of APAP hepatotoxicity through inhibiting an excessive accumulation of activated neutrophils. The development of a specific agonist for BLT1 could be useful for the prevention of APAP hepatotoxicity. PMID- 27404730 TI - Using the Delphi method to develop nursing-sensitive quality indicators for the NICU. AB - AIMS AND OBJECTIVES: To develop nursing-sensitive quality indicators consistent with current medical practices in Chinese neonatal intensive care units. BACKGROUND: The development of nursing-sensitive quality indicators has become a top priority in nursing management. To the best of our knowledge, there has been no objective, scientific and sensitive evaluation of the quality of neonatal intensive care unit nursing in China. DESIGN: A modified Delphi technique was used to seek opinions from experts about what should be used and prioritised as indicators of quality care in neonatal intensive care unit nursing. METHODS: Based on a literature review, we identified 21 indicators of nursing-sensitive quality in the neonatal intensive care unit. Our group of 11 consultants chose 13 indicators to be discussed using the Delphi method. In October and November 2014, 39 neonatal intensive care unit experts in 18 tertiary hospitals spread across six provinces participated in two rounds of Delphi panels. RESULTS: Of the 13 indicators discussed, 11 were identified as indicators of nursing-sensitive quality in the neonatal intensive care unit: rate of nosocomial infections, rate of accidental endotracheal extubation, rate of errors in medication administration, rate of treatment for pain, rate of peripheral venous extravasation, rate of compliance with handwashing techniques, incidence of pressure ulcers, incidence of noise, the bed-to-care ratio, the proportion of nurses with greater than five years neonatal intensive care unit experience and incidence of retinopathy. CONCLUSIONS: The 11 neonatal intensive care unit nursing-sensitive indicators identified by the Delphi method integrated with basic Chinese practices provide a basis for nursing management and the monitoring of nursing quality. RELEVANCE TO CLINICAL PRACTICE: This study identified nursing sensitive quality indicators for neonatal intensive care unit care that are suitable for current clinical practice in China. PMID- 27404732 TI - On the Importance of Gravity in DNAPL Invasion of Saturated Horizontal Fractures. AB - Invasion percolation (IP) models of dense non-aqueous phase liquid (DNAPL) invasion into saturated horizontal fractures typically neglect viscous and gravity forces, as it is assumed that capillarity dominates in many situations. An IP model simulating DNAPL invasion into saturated horizontal fractures was modified to include gravity as a local effect. The model was optimized using a genetic algorithm, and demonstrated that the inclusion of gravity is important for replicating the architecture of the DNAPL invasion pattern. The optimized gravity-included simulation showed the DNAPL invasion pattern to be significantly more representative of the experimentally observed pattern (80% accuracy) than did the optimized gravity-neglected simulation (70% accuracy). Additional simulations of DNAPL invasion in 360 randomly generated fractures were compared with and without gravity forces. These simulations showed that with increasing fracture roughness, the minimum difference between simulations with and without gravity increases to 35% for a standard deviation of the mid-aperture elevation field (SDz ) of 10 mm. Even for low roughness (SDz = 0.1 mm), the difference was as high as 30%. Furthermore, a scaled Bond Number is defined which includes data regarding DNAPL type, media type and statistical characteristics of the fracture. The value of this scaled Bond Number can be used to determine the conditions under which gravity should be considered when simulating DNAPL invasion in a macroscopically horizontal fracture. Finally, a set of equations defining the minimum and maximum absolute percentage difference between gravity-included and gravity-neglected simulations is presented based on the fracture and DNAPL characteristics. PMID- 27404731 TI - Ancestral Reconstruction. PMID- 27404733 TI - Determining Criteria to Predict Repeatability of Performance in Older Adults: Using Coefficients of Variation for Strength and Functional Measures. AB - Reliable measures of muscle strength and functional capacity in older adults are essential. The aim of this study was to determine whether coefficients of variation (CVs) of individuals obtained at the first session can infer repeatability of performance in a subsequent session. Forty-eight healthy older adults (mean age 68.6 +/- 6.1 years; age range 60-80 years) completed two assessment sessions, and on each occasion undertook: dynamometry for isometric and isokinetic quadriceps strength, 6 meter fast walk (6MFWT), timed up and go (TUG), stair climb and descent, and vertical jump. Significant linear relationships were observed between CVs in session 1 and the percentage difference between sessions 1 and 2 for torque at 60, 120, 240 and 360 degrees /s, 6MFWT, TUG, stair climb, and stair descent. The results of this study could be used to establish criteria for determining an acceptably reliable performance in strength and functional tests. PMID- 27404734 TI - Emotional interference and attentional processing in premenstrual syndrome. AB - BACKGROUND AND OBJECTIVES: Premenstrual syndrome (PMS) is characterized by menstrual cycle-related affective, behavioral, and/or somatic symptoms. By applying the emotional Stroop task (EST) the current study examined if changes in processing emotional information, which have been demonstrated in affective disorders, are also present in PMS. METHODS: Via online screening, telephone interviews, and daily records over two months 55 women for the PMS group (on the basis of the specific inclusion criteria and a prospectively confirmed PMS) and 55 'non-PMS' controls were recruited. All participants completed three emotional Stroop tasks (EST) with neutral and negative word, picture, and facial stimuli, during the follicular and luteal phase of the menstrual cycle. RESULTS: Mixed 2 * 2 univariate analyses of variance and post-hoc comparisons showed primarily a greater emotional Stroop effect with respect to picture and facial stimuli in the luteal menstrual cycle phase in women with PMS, compared to the control group. No significant group differences were observed for word stimuli. With respect to the facial stimuli, a kind of paradox effect was revealed (Stroop facilitation) in the PMS group. LIMITATIONS: This study provides important information regarding cognitive processes in women suffering from PMS that have to be interpreted in the light of the following limitations: a limited representativeness of the sample, the determination of menstrual cycle phases based on symptom diaries but not hormone levels, and a limited interpretability of our results as causal relationships. CONCLUSIONS: Our findings are in line with the assumption that alterations in cognitive-emotional processes are associated with PMS. Further research on the etiology of PMS should focus more on cognitive-emotional processing and its interaction with biological changes relating to the menstrual cycle. PMID- 27404736 TI - Nanoscale Control of Polymer Assembly on a Synthetic Catalyst-Bilayer System. AB - The use of the interior of self-assembled membrane as a template for polymer synthesis and assembly has long attracted the interest of chemists. However, it is difficult to utilize a lipid membrane as a chemical reactor for controlled assembly for polymers because lipid membrane is easily destabilized by loading of extraneous molecules. We found that a several-nanometer-thick bilayer vesicle made by self-assembly of an organic fullerene amphiphile doped with a metathesis catalyst serves as a nanosized chemical reactor in water, where a polymer is synthesized and assembled, depending on the affinity of the growing polymer to the organic groups on the amphiphile. This catalyst-bilayer system can thus control supramolecular assembly of the ester-functionalized polymer product into different nanoscale structures: a nanoparticle made of a single polymer chain and a nanocapsule made of several tens of polymer chains. PMID- 27404735 TI - Highly sensitive detection of lipopolysaccharides using an aptasensor based on hybridization chain reaction. AB - Lipopolysaccharides (LPS), integral components of the outer membrane of all gram negative bacteria, are closely associated with foodborne diseases such as fever, diarrhea and hypotension, and thus, the early and sensitive detection of LPS is necessary. In this study, an aptasensor assay based on hybridization chain reaction (HCR) was developed to detect LPS. Briefly, two complementary stable species of biotinylated DNA hairpins coexisted in solution until the introduction of a detection probe triggered a hybridization chain reaction cascade. The DNA conjugates specifically reacted with the LPS, which were captured by the ethanolamine aptamer attached to the reaction well surface. After optimizing the key reaction conditions, such as the reaction time of HCR, the amount of the capture probe and detection probes, the increase in the LPS concentration was readily measured by the optical density value, and a relatively low detection limit (1.73 ng/mL) was obtained, with a linear response range of 1-10(5 )ng/mL. The approach presented herein introduced the use of an aptasensor for LPS discrimination and HCR for signal amplification, offering a promising option for detecting LPS. PMID- 27404737 TI - Paradoxical Effect of Levetiracetam in Newly Diagnosed Type II Focal Cortical Dysplasia. AB - A paradoxical effect of antiepileptic drugs was defined as an increased seizure frequency or severity occurring shortly after introducing a drug considered effective for that kind of epilepsy. In addition, this effect should occur at nontoxic drug serum levels. So far, pathophysiological mechanisms underlying this phenomenon have not been clarified. Recent evidence suggests that the variability of drug effects may depend on precise intrinsic properties of dynamic networks involving the drug and its binding site. Although several reports of paradoxical seizure exacerbation have been reported for levetiracetam (LEV), a possible association with focal cortical dysplasia has never been described nor investigated. In this report, we document a paradoxical effect induced by LEV monotherapy in a patient with type II focal cortical dysplasia at LEV serum levels within the therapeutic range. A hint of pathophysiological hypothesis underlying this potential relationship will be also suggested. PMID- 27404738 TI - Acetyl-L-Carnitine Augmentation of Clozapine in Partial-Responder Schizophrenia: A 12-Week, Open-Label Uncontrolled Preliminary Study. AB - OBJECTIVES: This was the first 12-week, open-label, uncontrolled trial aimed at exploring the efficacy of acetyl-L-carnitine (ALC) add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 schizophrenia patients with suboptimal clinical response despite receiving clozapine (CLZ) monotherapy at the highest tolerated dosage. METHODS: After clinical (Positive and Negative Symptoms Scale [PANSS]) and neuropsychological (Wisconsin Card Sorting Test, Stroop Color Word Test, Verbal Fluency Test) assessments, patients received 1 g/d of ALC for 12 weeks. RESULTS: A final sample of 9 subjects completed the study. Acetyl-L carnitine augmentation of CLZ significantly reduced only PANSS domains "positive" (P = 0.049); at end point, only 2 subjects (22.2% of the completers) reached a minimal improvement (25% reduction in PANSS total score). No significant differences emerged in cognitive performances at the end of the study; effect sizes were small in each explored cognitive dimension. CONCLUSIONS: The findings provide preliminary evidence that ALC added to ongoing CLZ treatment appeared to be ineffective to improve symptoms in schizophrenia patients who have failed to respond sufficiently to CLZ. Further trials with adequately powered methodology are needed to identify which augmentation strategies are more effective in schizophrenia patients showing a suboptimal response to CLZ. PMID- 27404739 TI - Design and expression of peptides with antimicrobial activity against Salmonella typhimurium. AB - We showed previously that insertion of Synechocystis Delta12 -desaturase in salmonella's membrane alters membrane physical state (MPS), followed by the expression of stress genes causing inability to survive within murine macrophages (MPhi). Recently, we showed that expression of one membrane lipid domain (MLD) of Delta12 -desaturase (ORF200) interferes with salmonella MPS, causing loss of virulence in mice and immunoprotection. Here, we postulate that an alpha antimicrobial peptide (alpha-AMP) intercalates within membrane lipids, and depending on its amino acid sequence, it does so within specific key sensors of MLD. In this study, we choose as target for a putative synthetic AMP, PhoP/PhoQ, a sensor that responds to low Mg2+ concentration. We synthesised a modified DNA fragment coding for an amino acid sequence (NUF) similar to that fragment and expressed it in salmonella typhimurium. We showed that the pattern of gene expression controlled by PhoP/PhoQ highlights dysregulation of pathways involving phospholipids biosynthesis, stress proteins and genes coding for antigens. RNA Seq of strain expressing ORF200 showed that the pattern of those genes is also altered here. Accumulation of NUF conferred temporary immunoprotection. This represents a powerful procedure to address synthetic alpha-AMPs to a specific MLD generating live non-virulent bacterial strains. PMID- 27404740 TI - Continuous leaky-wave scanning using periodically modulated spoof plasmonic waveguide. AB - The plasmonic waveguide made of uniform corrugated metallic strip can support and guide spoof surface plasmon polaritons (SSPPs) with high confinements. Here, we propose periodically-modulated plasmonic waveguide composed of non-uniform corrugated metallic strip to convert SSPPs to radiating waves, in which the main beam of radiations can steer continuously as the frequency changes. To increase the radiation efficiency of the periodically-modulated plasmonic waveguide at the broadside, an asymmetrical plasmonic waveguide is further presented to reduce the reflections and realize continuous leaky-wave scanning. Both numerical simulations and experimental results show that the radiation efficiency can be improved greatly and the main beam of leaky-wave radiations can steer from the backward quadrant to the forward quadrant, passing through the broadside direction, which generally is difficult to be realized by the common leaky-wave antennas. PMID- 27404741 TI - A Donor-Acceptor Conjugated Polymer with Alternating Isoindigo Derivative and Bithiophene Units for Near-Infrared Modulated Cancer Thermo-Chemotherapy. AB - Conjugated polymers containing alternating donor/acceptor units have strong and sharp absorbance peaks in near-infrared (NIR) region, which could be suitable for photothermal therapy. However, these polymers as photothermal transducers are rarely reported because of their water insolubility, which limits their applications for cancer therapy. Herein, we report the donor-acceptor conjugated polymer PBIBDF-BT with alternating isoindigo derivative (BIBDF) and bithiophene (BT) units as a novel photothermal transducer, which exhibited strong near infrared (NIR) absorbance due to its low band gap (1.52 eV). To stabilize the conjugated polymer physiological environments, we utilized an amphiphilic copolymer, poly(ethylene glycol)-block-poly(hexyl ethylene phosphate) (mPEG-b PHEP), to stabilize PBIBDF-BT-based nanoparticles (PBIBDF-BT@NPPPE) through a single emulsion method. The obtained nanoparticles PBIBDF-BT@NPPPE showed great stability in physiological environments and excellent photostability. Moreover, the PBIBDF-BT@NPPPE exhibited high photothermal conversion efficiency, reaching 46.7%, which is relatively high compared with those of commonly used materials for photothermal therapy. Accordingly, in vivo and in vitro experiments demonstrated that PBIBDF-BT@NPPPE exhibits efficient photothermal anticancer efficacy. More importantly, PBIBDF-BT@NPPPE could simultaneously encapsulate other types of therapeutic agents though hydrophobic interactions with the PHEP core and achieve NIR-triggered intracellular drug release and a synergistic combination therapy of thermo-chemotherapy for the treatment of cancer. PMID- 27404744 TI - Coming in sportsmedicine. PMID- 27404742 TI - Force and Position Control in Humans - The Role of Augmented Feedback. AB - During motor behaviour, humans interact with the environment by for example manipulating objects and this is only possible because sensory feedback is constantly integrated into the central nervous system and these sensory inputs need to be weighted in order meet the task specific goals. Additional feedback presented as augmented feedback was shown to have an impact on motor control and motor learning. A number of studies investigated whether force or position feedback has an influence on motor control and neural activation. However, as in the previous studies the presentation of the force and position feedback was always identical, a recent study assessed whether not only the content but also the interpretation of the feedback has an influence on the time to fatigue of a sustained submaximal contraction and the (inhibitory) activity of the primary motor cortex using subthreshold transcranial magnetic stimulation. This paper describes one possible way to investigate the influence of the interpretation of feedback on motor behaviour by investigating the time to fatigue of submaximal sustained contractions together with the neuromuscular adaptations that can be investigated using surface EMG. Furthermore, the current protocol also describes how motor cortical (inhibitory) activity can be investigated using subthreshold TMS, a method known to act solely on the cortical level. The results show that when participants interpret the feedback as position feedback, they display a significantly shorter time to fatigue of a submaximal sustained contraction. Furthermore, subjects also displayed an increased inhibitory activity of the primary cortex when they believed to receive position feedback compared when they believed to receive force feedback. Accordingly, the results show that interpretation of feedback results in differences on a behavioural level (time to fatigue) that is also reflected in interpretation-specific differences in the amount of inhibitory M1 activity. PMID- 27404743 TI - Editor's notes. PMID- 27404747 TI - Scanning sports. PMID- 27404748 TI - At the Back of the Pack. PMID- 27404750 TI - Exercise Testing, Training, and Beta-Adrenergic Blockade. PMID- 27404749 TI - Epistaxis in the Athlete. AB - In brief: Epistaxis is common among nonathletes as well as athletes, but because athletes may be more likely to sustain nasal/facial trauma, they probably are more at risk for epistaxis than nonathletes. An epistaxis tray containing the proper equipment should be kept readily available to be used to stop bleeding that does not stop spontaneously. Supplies should include cotton pledgets, antibiotic ointment, a nasal suction tip, a suction source, a topical anesthetic/vasoconstrictor, and more. In some cases reduction of an associated nasal fracture may be required before bleeding will stop. The author outlines the local and systemic causes of epistaxis, the field and hospital treatment for anterior and posterior epistaxis, and the possible complications. PMID- 27404751 TI - Arteriovenous Fistula Development After Posterior Compartment Fasciotomy to Treat Shin Splints. AB - In brief: This case report presents an unusual complication in a distance runner who was treated for the shin splint syndrome. Following release of the deep posterior fascial compartment, he had mild erythema and swelling in the region of his incision. He could not bear full weight on his left leg because of pain. An arteriogram obtained approximately six months later showed an arteriovenous fistula, which was subsequently treated with resection and neurolysis of the saphenous nerve. The patient improved but did not reach his previous level of athletic performance. Recommendations for preventing this complication are outlined, and the use of the term shin splints is discussed. PMID- 27404752 TI - Basketball Injuries: An Overview. AB - In brief: Why have basketball injuries escalated? The author points out that before 1960 basketball was largely a no-contact sport. Since then the amount of body contact allowed has increased, players are larger, and more athletes are playing basketball. In addition to these and other possible reasons for the increase in injuries, the author describes common basketball injuries-contusions, sprains, strains, inflammatory conditions, and stress fractures. He also outlines steps for diagnosis and treatment and makes recommendations. PMID- 27404753 TI - Aerobic Dance Injuries Among Instructors and Students. AB - In brief: Aerobic dancing is a popular fitness activity in Japan, primarily among young women. To identify and characterize the injuries associated with aerobic dance, 161 instructors and 800 students from 13 Japanese fitness facilities were surveyed. Results showed an injury rate of 72.4% for instructors and 22.8% for students. The lower leg and foot were the most common injury sites for instructors and students, respectively. Though these results seem to indicate that aerobic dance is hazardous, the number of injuries per 100 hours of participation was only 0.17 for instructors and 0.15 for students. Most aerobic dance injuries seem to be caused by overuse; thus, moderating the frequency and duration of participation and individualizing programs could reduce the number of injuries that occur. PMID- 27404754 TI - Self-Reported Use of Anabolic-Androgenic Steroids by Elite Power Lifters. AB - In brief: Sixty-one athletes competed in the 1987 National Championship of the US Powerlifting Federation; all were surveyed to obtain information on anabolic androgenic steroids regarding attitudes, patterns of use, and health effects. Of the 45 who responded to the survey, 15 admitted having used steroids. In a follow up telephone interview of 20 of the competitors, 11 reported previous steroid use. The reason given most often for using steroids was improved athletic performance; the most common side effects reported were heightened libido, acne, and increased body hair. The small number of admitted users suggests that underreporting took place; this level of use probably represents the lower bound of steroid use among power lifters. PMID- 27404755 TI - Prophylactic Knee Braces: Where Do They Stand? AB - Whether the research takes place on the playing field or in the laboratory, it doesn't seem to matter: The effectiveness of knee braces in preventing injuries remains inconclusive. PMID- 27404756 TI - Reflections on the Medical Aspects of the 1988 Olympic Summer Games. PMID- 27404760 TI - Strength and Endurance of the Lower Arm Muscles. PMID- 27404761 TI - Enhanced colon cancer chemoprevention of curcumin by nanoencapsulation with whey protein. AB - To improve bioavailability and enhance colon cancer prevention ability of curcumin, whey protein was used to nanoencapsulate at three different ratios such as 70:30, 50:50 and 35:65 for the first time. The drug loading, entrapment efficiency and structural changes of curcumin was confirmed by quantitative NMR spectroscopy. The nanoparticles prepared using the three ratios had an average diameters of 236.5+/-8.8, 212+/-3.4, and 187+/-11.4nm, as well as zeta (zeta) potentials of -13.1,-9.26, and -4.63mV, respectively, at pH 7.0. The cytotoxicity assay was performed for human colon and prostate cancer (SW480 and LNCap) by MTT assay and results showed significantly higher cytotoxicity of nanoencapsulated curcumin (NEC) (equivalent to 30.91, 20.70 and 16.86uM of NEC-1, 2 and 3 respectively), as compared to plain curcumin at 50uM after 72h of treatment. Cytotoxicity was also confirmed by microscopy of treated cells stained with acridine orange and propidium iodide. The cells treated with 50uM of curcumin, 30.91uM (NEC-1), 20.70uM (NEC-2) and 16.86uM (NEC-3) showed enhanced activation of p53 and elevated bax/Bcl2 expression (NEC-3), increased cytochrome-c in cytosol (NEC-2) confirming the enhanced cytotoxicity. To confirm the increased bioavailability, the intracellular curcumin was measured using fluorescence intensity. The fluorescent signal for intracellular curcumin was increased by 12, 30, and 21% for NEC-1, NEC-2, and NEC-3 respectively as compared to plain curcumin at 4h. Based on these results, we conclude that nanoencapsulated curcumin with whey protein will have potential to be considered for clinical applications for future studies. PMID- 27404762 TI - Clean Sampling and Analysis of River and Estuarine Waters for Trace Metal Studies. AB - Most of the trace metal concentrations in ambient waters obtained a few decades ago have been considered unreliable owing to the lack of contamination control. Developments of some techniques aiming to reduce trace metal contamination in the last couple of decades have resulted in concentrations reported now being orders of magnitude lower than those in the past. These low concentrations often necessitate preconcentration of water samples prior to instrumental analysis of samples. Since contamination can appear in all phases of trace metal analyses, including sample collection (and during preparation of sampling containers), storage and handling, pretreatments, and instrumental analysis, specific care needs to be taken in order to reduce contamination levels at all steps. The effort to develop and utilize "clean techniques" in trace metal studies allows scientists to investigate trace metal distributions and chemical and biological behavior in greater details. This advancement also provides the required accuracy and precision of trace metal data allowing for environmental conditions to be related to trace metal concentrations in aquatic environments. This protocol that is presented here details needed materials for sample preparation, sample collection, sample pretreatment including preconcentration, and instrumental analysis. By reducing contamination throughout all phases mentioned above for trace metal analysis, much lower detection limits and thus accuracy can be achieved. The effectiveness of "clean techniques" is further demonstrated using low field blanks and good recoveries for standard reference material. The data quality that can be obtained thus enables the assessment of trace metal distributions and their relationships to environmental parameters. PMID- 27404763 TI - Microscopic insight into the DNA condensation process of a zwitterion functionalized polycation. AB - Zwitterion-functionalized polycations are ideal gene carriers with long circulation, high cellular uptaking and low cell viability. However, the trade off between the DNA condensation efficiency and the cell viability must be addressed. The purpose of this study is to provide a microscopic insight into the DNA condensation process and to explore the effect of a zwitterionic block of zwitterion-functionalized polycation, which is of great significance in designing novel gene delivery systems. Poly[2-(dimethylamino)ethyl methacrylate-b (sulfobetaine methacrylate)] (PDMAEMA-b-PSBMA) copolymers were synthesized and used as the model systems. Different from the conventional concept that the PSBMA zwitterionic block act only as the "stealthy" groups, the subtle differences in physical and colloidal characteristics between the polycation/DNA polyplexes show that the PSBMA segment is capable of wrapping DNA attributed to the quaternary ammonium cations, without compromising the DNA condensation capability. On the other hand, the incorporation of PSBMA block reduces the surface charge of the polyplexes, which substantially result in the inefficient transfection and the reduced cytotoxicity. PMID- 27404764 TI - Quantitative Conductive Atomic Force Microscopy on Single-Walled Carbon Nanotube Based Polymer Composites. AB - Conductive atomic force microscopy (C-AFM) is a valuable technique for correlating the electrical properties of a material with its topographic features and for identifying and characterizing conductive pathways in polymer composites. However, aspects such as compatibility between tip material and sample, contact force and area between the tip and the sample, tip degradation and environmental conditions render quantifying the results quite challenging. This study aims at finding the suitable conditions for C-AFM to generate reliable, reproducible, and quantitative current maps that can be used to calculate the resistance in each point of a single-walled carbon nanotube (SWCNT) network, nonimpregnated as well as impregnated with a polymer. The results obtained emphasize the technique's limitation at the macroscale as the resistance of these highly conductive samples cannot be distinguished from the tip-sample contact resistance. Quantitative C AFM measurements on thin composite sections of 150-350 nm enable the separation of sample and tip-sample contact resistance, but also indicate that these sections are not representative for the overall SWCNT network. Nevertheless, the technique was successfully used to characterize the local electrical properties of the composite material, such as sample homogeneity and resistance range of individual SWCNT clusters, at the nano- and microscale. PMID- 27404765 TI - Which Febrile Children With Sickle Cell Disease Need a Chest X-Ray? AB - OBJECTIVE: Controversy exists regarding which febrile children with sickle cell disease (SCD) should receive a chest x-ray (CXR). Our goal is to provide data informing the decision of which febrile children with SCD presenting to the emergency department (ED) require a CXR to evaluate for acute chest syndrome (ACS). METHODS: Retrospective chart review of children ages 3 months to 21 years with SCD presenting to the ED at one of two academic children's hospitals with fever >=38.5 degrees C between January 1, 2010, and December 31, 2012. Demographic characteristics, respiratory symptoms, and laboratory results were abstracted. The primary outcome was the presence of ACS. Binary recursive partitioning was performed to determine predictive factors for a diagnosis of ACS. RESULTS: A total of 185 (10%) of 1,837 febrile ED visits met ACS criteria. The current National Heart, Lung, and Blood Institute (NHLBI) consensus criteria for obtaining a CXR (shortness of breath, tachypnea, cough, or rales) identified 158 (85%) of ACS cases, while avoiding 825 CXRs. Obtaining a CXR in children with NHLBI criteria or chest pain and in children without those symptoms but with a white blood cell (WBC) count >=18.75 * 109 /L or a history of ACS identified 181 (98%), while avoiding 430 CXRs. CONCLUSION: Children with SCD presenting to the ED with fever and shortness of breath, tachypnea, cough, rales, or chest pain should receive a CXR due to high ACS rates. A higher WBC count or history of ACS in a child without one of those symptoms may suggest the need for a CXR. Prospective validation of these criteria is needed. PMID- 27404766 TI - Moving evidence into practice: cost analysis and assessment of macaques' sustained behavioral engagement with videogames and foraging devices. AB - Environmental enrichment plans for captive nonhuman primates often include provision of foraging devices. The rationale for using foraging devices is to promote species-typical activity patterns that encourage physical engagement and provide multi-sensory stimulation. However, these devices have been shown to be ineffective at sustaining manipulation over long periods of time, and often produce minimal cognitive engagement. Here we use an evidence-based approach to directly compare the amount of object-directed behavior with a foraging device and a computer-based videogame system. We recorded 11 adult male rhesus monkeys' interactions with a foraging device and two tasks within a joystick videogame cognitive test battery. Both techniques successfully produced high levels of engagement during the initial 20 min of observation. After 1 hr the monkeys manipulated the foraging device significantly less than the joystick, F(2,10) = 43.93, P < 0.0001. Subsequent testing showed that the monkeys engaged in videogame play for the majority of a 5 hr period, provided that they received a 94 mg chow pellet upon successful completion of trials. Using a model approach, we developed previously as a basis for standardized cost:benefit analysis to inform facility decisions, we calculated the comprehensive cost of incorporating a videogame system as an enrichment strategy. The videogame system has a higher initial cost compared to widely-used foraging devices, however, the ongoing labor and supply costs are relatively low. Our findings add to two decades of empirical studies by a number of laboratories that have demonstrated the successful use of videogame-based systems to promote sustained non-social cognitive engagement for macaques. The broader significance of the work lies in the application of a systematic approach to compare and contrast enrichment strategies and encourage evidence-based decision making when choosing an enrichment strategy in a manner that promotes meaningful cognitive enrichment to the animals. PMID- 27404767 TI - Hot Flash Frequency and Blood Pressure: Data from the Study of Women's Health Across the Nation. AB - BACKGROUND: Vasomotor symptoms (VMS) are highly prevalent among midlife women and have been associated with subclinical cardiovascular disease (CVD). However, the association between VMS frequency and risk factors such as hypertension (HTN) remains unclear. MATERIALS AND METHODS: We examined VMS frequency and blood pressure (BP) among 2839 participants of the Study of Women's Health Across the Nation (SWAN), a multiethnic, prospective, study of women enrolled from seven U.S. sites between November 1995 and October 1997. Women were age 42-52, with no history of CVD, and not postmenopausal at baseline. VMS was defined by the number of days a woman reported VMS over the 2-week period before each annual visit. Frequent VMS was defined as >=6 days of VMS; less frequent VMS was defined 1-5 days of symptoms with asymptomatic women the reference group. BP was measured at each visit in addition to demographic and clinic factors. RESULTS: At baseline, 298 women reported frequent VMS, 794 less frequent VMS and 1747 no VMS. More frequent baseline VMS was associated with higher BP. Compared to no VMS, baseline VMS was associated with HTN (odds ratio [OR] 1.47, 95% confidence interval [CI]; 1.14-1.88 for infrequent VMS, and OR 1.40, (95% CI; 0.97-2.02 for frequent VMS). Risk for incident pre-HTN or HTN during follow-up was increased among women with frequent VMS (hazard ratio of 1.39, 95% CI; 1.09-1.79) after adjustment for multiple covariates. CONCLUSION: Women with VMS may be more likely to develop HTN compared to women without VMS. Further research related to VMS including frequency of symptoms is warranted. PMID- 27404768 TI - Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015. AB - This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates. PMID- 27404770 TI - Quantification of intracellular payload release from polymersome nanoparticles. AB - Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 +/- 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology. PMID- 27404772 TI - Psychotherapy, psychoanalysis and urban poverty in Argentina. AB - Based on ethnographic research carried out in the Buenos Aires Metropolitan Area, this paper examines the views of social actors on the psychoanalytically-oriented psychotherapy focused on marginalized populations. From Foucault's perspective on the forms of truth-telling, the aim of this paper is to analyze, as a preliminary research report, treatments according to the native ways of speaking and listening, which dominate the description of therapeutic experiences of patients who come to the treatment without any professional intermediation. The neoliberal transformations of the past decades in Argentina changed both the landscape of the public health system and the daily lives of marginalized people. Considering such changes, this paper examines the ways in which verbal actions (speaking and listening) take place in psychotherapy and mark the course not only of treatments but also the temporal rhythms of their development, and their various levels of efficacy. Finally, the discussion focuses on how ways of speaking and listening in treatments are modeled not only by institutional dynamics but also by the characteristics these verbal activities take in everyday life under the logics of power that prevail over them. PMID- 27404771 TI - Children with autism spectrum disorder have reduced otoacoustic emissions at the 1 kHz mid-frequency region. AB - Autism spectrum disorder (ASD) is a behaviorally diagnosed disorder of early onset characterized by impairment in social communication and restricted and repetitive behaviors. Some of the earliest signs of ASD involve auditory processing, and a recent study found that hearing thresholds in children with ASD in the mid-range frequencies were significantly related to receptive and expressive language measures. In addition, otoacoustic emissions have been used to detect reduced cochlear function in the presence of normal audiometric thresholds. We were interested then to know if otoacoustic emissions in children with normal audiometric thresholds would also reveal differences between children with ASD and typical developing (TD) controls in mid-frequency regions. Our objective was to specifically measure baseline afferent otoacoustic emissions (distortion-product otoacoustic emissions [DPOAEs]), transient-evoked otoacoustic emissions (TrOAEs), and efferent suppression, in 35 children with high functioning ASD compared with 42 aged-matched TD controls. All participants were males 6-17 years old, with normal audiometry, and rigorously characterized via Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Children with ASD had greatly reduced DPOAE responses in the 1 kHz frequency range, yet had comparable DPOAE responses at 0.5 and 4-8 kHz regions. Furthermore, analysis of the spectral features of TrOAEs revealed significantly decreased emissions in ASD in similar frequencies. No significant differences were noted in DPOAE or TrOAE noise floors, middle ear muscle reflex activity, or efferent suppression between children with ASD and TD controls. In conclusion, attention to specific-frequency deficits using non-invasive measures of cochlear function may be important in auditory processing impairments found in ASD. Autism Res 2017, 10: 337-345. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27404773 TI - Synthesis and Anti-Proliferative Activity of Sulfanyltriazolylnaphthalenols and Sulfanyltriazolylnaphthalene-1,4-diones. AB - A series of new sulfanyltriazolylnaphthalenols (10a-f and 13a-f) and sulfanyltriazolylnaphthalene-1,4-diones (14a-f) were synthesized and evaluated against a panel of cancer cell lines. Among the tested compounds, 10b and 10d showed the best anti-proliferative activity with GI50 values ranging from 2.72 to 10 and 3.13 to 13.1 uM, respectively, in several of the tumor cell lines tested. Compound 10d is highly selective toward leukemia cell lines and can be regarded as a good model for the development of new anti-leukemic agents. PMID- 27404775 TI - Reply to Comment by Gallina et al on "Progression of Normal-Tension Glaucoma After Ventriculoperitoneal Shunt to Decrease Cerebrospinal Fluid Pressure". J Glaucoma 2016; 25: e50-e52. PMID- 27404774 TI - Incidence of mature adipocytic component within cutaneous smooth muscle neoplasms. AB - Angioleiomyoma is a benign smooth muscle tumor of the subcutis. The presence of mature adipocytes has been described in this tumor under the rubric of 'angiolipoleiomyoma' or, erroneously, 'angiomyolipoma' (these are not PEComas). Previous studies have found adipocytes in only 2-3% of angioleiomyoma. Anecdotally, the incidence appeared to be greater than this in our practice. Moreover, the presence of adipocytes has not been evaluated in pilar leiomyoma or cutaneous leiomyosarcoma. We searched the pathology archives from 2007 to 2014 for all cutaneous and subcutaneous leiomyoma and leiomyosarcoma; cases were reviewed to confirm the diagnosis and evaluate for mature adipocytes. Seven of 73 total cases (10%) contained mature adipocytes: 1 of 33 pilar leiomyoma (3%), 4 of 22 angioleiomyoma (18%) and 2 of 18 leiomyosarcoma (11%). In our series, the 18% incidence of 'angioleiomyoma with fat' (our preferred terminology) is higher than the previously reported incidence of 2-3%. We also report the rare presence of mature adipocytes within pilar leiomyoma and cutaneous leiomyosarcoma, a finding not previously reported to our knowledge. Mature adipocytes may be present within cutaneous and subcutaneous leiomyomas and leiomyosarcomas and should not detract from the diagnosis or lead to concern for an adipocytic neoplasm or PEComa. PMID- 27404776 TI - Late-onset Hypotony Maculopathy After Trabeculectomy in a Highly Myopic Patient With Juvenile Open-angle Glaucoma. AB - Hypotony maculopathy is a sight-threatening complication after trabeculectomy. We report on a 34-year-old man with juvenile open-angle glaucoma and high myopia, who developed hypotony maculopathy 14 years after trabeculectomy without bleb leak. This represents the longest known period from trabeculectomy to the development of hypotony maculopathy without bleb leak. The possible mechanisms for the development of late-onset hypotony maculopathy in the highly myopic patient are progressive scleral thinning, reduced scleral rigidity, and scleral morphologic change with aging. These changes might weaken the biomechanical properties of sclera and then contribute to the collapse of the scleral wall during hypotony. This case serves as a reminder that hypotony maculopathy can happen up to 14 years after tabeculectomy even without bleb leak and hypotony should be avoided after trabeculectomy in highly myopic patients with juvenile open-angle glaucoma. PMID- 27404777 TI - [Not Available]. AB - The Swedish Dental and Pharmaceutical Benefits Agency (TLV) is the government body responsible for deciding whether outpatient drugs are to be included in the pharmaceutical benefits scheme. This paper analyzed all decisions made by TLV between 2005 and 2011 in order to investigate how the cost-effectiveness of a drug and the severity of the disease the drug targets affected the likelihood of subsidy of a drug. We find that TLV places significant weight on both the cost effectiveness, measured as the cost per Quality-Adjusted Life Year (QALY), and disease severity. We also find that the higher cost per QALY approved for severe diseases is mainly represented by cancer drugs. Drugs targeting severe diseases other than cancer have a similar cost per QALY as for non-severe diseases. PMID- 27404779 TI - [Not Available]. PMID- 27404778 TI - [Not Available]. PMID- 27404780 TI - [Not Available]. PMID- 27404782 TI - [Not Available]. PMID- 27404781 TI - [Not Available]. PMID- 27404784 TI - [Not Available]. PMID- 27404783 TI - [Not Available]. PMID- 27404785 TI - [Not Available]. PMID- 27404786 TI - [Not Available]. PMID- 27404787 TI - [Not Available]. PMID- 27404790 TI - Carbon Nanotubes Application in the Extraction Techniques of Pesticides: A Review. AB - Carbon nanotubes (CNTs) are currently one of the most promising groups of materials with some interesting properties, such as lightness, rigidity, high surface area, high mechanical strength in tension, good thermal conductivity or resistance to mechanical damage. These unique properties make CNTs a competitive alternative to conventional sorbents used in analytical chemistry, especially in extraction techniques. The amount of work that discusses the usefulness of CNTs as a sorbent in a variety of extraction techniques has increased significantly in recent years. In this review article, the most important feature and different applications of solid-phase extraction (SPE), including, classical SPE and dispersive SPE using CNTs for pesticides isolation from different matrices, are summarized. Because of high number of articles concerning the applicability of carbon materials to extraction of pesticides, the main aim of proposed publication is to provide updated review of the latest uses of CNTs by covering the period 2006-2015. Moreover, in this review, the recent papers and this one, which are covered in previous reviews, will be addressed and particular attention has been paid on the division of publications in terms of classes of pesticides, in order to systematize the available literature reports. PMID- 27404789 TI - Potent response of QS-21 as a vaccine adjuvant in the skin when delivered with the Nanopatch, resulted in adjuvant dose sparing. AB - Adjuvants play a key role in boosting immunogenicity of vaccines, particularly for subunit protein vaccines. In this study we investigated the induction of antibody response against trivalent influenza subunit protein antigen and a saponin adjuvant, QS-21. Clinical trials of QS-21 have demonstrated the safety but, also a need of high dose for optimal immunity, which could possibly reduce patient acceptability. Here, we proposed the use of a skin delivery technology - the Nanopatch - to reduce both adjuvant and antigen dose but also retain its immune stimulating effects when compared to the conventional needle and syringe intramuscular (IM) delivery. We have demonstrated that Nanopatch delivery to skin requires only 1/100(th) of the IM antigen dose to induce equivalent humoral response. QS-21 enhanced humoral response in both skin and muscle route. Additionally, Nanopatch has demonstrated 30-fold adjuvant QS-21 dose sparing while retaining immune stimulating effects compared to IM. QS-21 induced localised, controlled cell death in the skin, suggesting that the danger signals released from dead cells contributed to the enhanced immunogenicity. Taken together, these findings demonstrated the suitability of reduced dose of QS-21 and the antigen using the Nanopatch to enhance humoral responses, and the potential to increase patient acceptability of QS-21 adjuvant. PMID- 27404791 TI - Comparison of Three Visual Field Tests in Children: Frequency Doubling Test, 24-2 and 30-2 SITA Perimetry. AB - BACKGROUND: To investigate the reliability of FDT and 24-2 and 30-2 Humphrey perimetry in children. METHODS: We retrospectively reviewed the records corresponding to 274 eyes of children aged 6-12 years, who underwent FDT and 30-2 and 24-2 Humphrey visual field testing from January 2011 through March 2013. Each test group was divided into two subgroups: a normal visual acuity subgroup (> 0.8 Snellen, group 1) and a low visual acuity subgroup (<=0.8 Snellen, group 2). Reliability indexes such as fixation losses, test duration, and the number and rate of false-positive errors were analyzed. RESULTS: In both subgroups, test duration was shortest for 24-2 perimetry (group 1: p < 0.0001; group 2: p < 0.0001). FDT was associated with lower rates of fixation loss, false positive errors, and false negative errors than 30-2 perimetry. However, the fixation loss rate of FDT was only significantly lower under the subgroup analysis. The normal visual acuity subgroup had a higher MD score on FDT vs. 30-2 perimetry (P = 0.028). However, the PSD was similar for all tests. CONCLUSION: This reliability study showed that FDT perimetry is superior to 30-2 SITA perimetry. There was no significant difference in the reliability indexes for FDT and 24-2 SITA perimetry; thus, when considering test duration and reliability, 24-2 SITA perimetry appears to be the optimal choice in pediatric patients. PMID- 27404794 TI - The immunomodulatory role of the hypothalamus-pituitary-gonad axis: Proximate mechanism for reproduction-immune trade offs? AB - The present review discusses the communication between the hypothalamic-pituitary gonad (HPG) axis and the immune system of vertebrates, attempting to situate the HPG-immune interaction into the context of life history trade-offs between reproductive and immune functions. More specifically, (i) we review molecular and cellular interactions between hormones of the HPG axis, and, as far as known, the involved mechanisms on immune functions, (ii) we evaluate whether the HPG-immune crosstalk serves as proximate mechanism mediating reproductive-immune trade-offs, and (iii) we ask whether the nature of the HPG-immune interaction is conserved throughout vertebrate evolution, despite the changes in immune functions, reproductive modes, and life histories. In all vertebrate classes studied so far, HPG hormones have immunomodulatory functions, and indications exist that they contribute to reproduction-immunity resource trade-offs, although the very limited information available for most non-mammalian vertebrates makes it difficult to judge how comparable or different the interactions are. There is good evidence that the HPG-immune crosstalk is part of the proximate mechanisms underlying the reproductive-immune trade-offs of vertebrates, but it is only one factor in a complex network of factors and processes. The fact that the HPG immune interaction is flexible and can adapt to the functional and physiological requirements of specific life histories. Moreover, the assumption of a relatively fixed pattern of HPG influence on immune functions, with, for example, androgens always leading to immunosuppression and estrogens always being immunoprotective, is probably oversimplified, but the HPG-immune interaction can vary depending on the physiological and envoironmental context. Finally, the HPG-immune interaction is not only driven by resource trade-offs, but additional factors such as, for instance, the evolution of viviparity shape this neuroendocrine-immune relationship. PMID- 27404793 TI - Cholinergic genetics of visual attention: Human and mouse choline transporter capacity variants influence distractibility. AB - The basal forebrain cholinergic projection system to the cortex mediates essential aspects of visual attention performance, including the detection of cues and the response to performance challenges (top-down control of attention). Higher levels of top-down control are mediated via elevated levels of cholinergic neuromodulation. The neuronal choline transporter (CHT) strongly influences the synthesis and release of acetylcholine (ACh). As the capacity of the CHT to import choline into the neuron is a major, presynaptic determinant of cholinergic neuromodulation, we hypothesize that genetically-imposed CHT capacity variation impacts the balance of bottom-up versus top-down control of visual attention. Following a brief review of the cognitive concepts relevant for this hypothesis, we describe the key results from our research in mice and humans that possess genetically-imposed changes in choline uptake capacity. CHT subcapacity is associated with poor top-down attentional control and attenuated (cholinergic) activation of right frontal regions. Conversely, mice overexpressing the CHT, and humans expressing a CHT variant hypothesized to enhance choline transporter function, are relatively resistant to challenges of visual attention performance. Genetic or environmental modulation of CHT expression and function may be associated with vulnerabilities for cognitive disorders. PMID- 27404796 TI - Corrigendum: Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development. PMID- 27404795 TI - Histone deacetylase inhibitor vorinostat (SAHA, MK0683) perturb miR-9-MCPIP1 axis to block IL-1beta-induced IL-6 expression in human OA chondrocytes. AB - AIM OF THE STUDY: High levels of IL-6 are believed to contribute to osteoarthritis (OA) pathogenesis. The expression of IL-6 is regulated post transcriptionally by the miR-9-MCPIP-1 axis in chondrocytes. Vorinostat (SAHA) inhibits the IL-6 expression in OA chondrocytes. We investigated whether SAHA suppresses the expression of IL-6 by perturbing the miR-9-MCPIP1 axis in OA chondrocytes under pathological conditions. MATERIALS AND METHODS: OA chondrocytes were isolated by enzymatic digestion and treated with IL-1beta in the absence or presence of SAHA. Genes and protein expression levels were determined by TaqMan assays and Western blotting, respectively. Secreted IL-6 was quantified by enzyme linked immunosorbent assay (ELISA). MCPIP1 promoter deletion mutants were generated by polymerase chain reaction (PCR). Promoter recruitment of transcription factors was determined by ChIP. Nuclear run-on was employed to measure the ongoing transcription. siRNA-mediated knockdown of the CEBPalpha expression was employed for loss of function studies. RESULTS: Expression of MCPIP1 was high in SAHA treated OA chondrocytes but expression of IL-6 mRNAs and secreted IL-6 were reduced by ~70%. SAHA suppressed the expression of miR-9 but enhanced the activity of the MCPIP1 promoter localized to a 156bp region which also harbors the binding site for CEBPalpha. Treatment with SAHA enhanced the recruitment of CEBPalpha to the MCPIP1 promoter. Ectopically expressed CEBPalpha enhanced the promoter activity and the expression of MCPIP1 while siRNA-mediated knockdown of CEBPalpha inhibited the expression of MCPIP1. CONCLUSIONS: Taken together our data indicate that SAHA-mediated suppression of the IL-6 expression is achieved through increased recruitment of CEBPalpha to the MCPIP1 promoter and by relieving the miR-9-mediated inhibition of MCPIP1 expression in OA chondrocytes. PMID- 27404797 TI - Antiplatelet therapy and outcome in patients undergoing surgery following coronary stenting: Results of the surgery after stenting registry. AB - OBJECTIVES: The aim of the present study was to define the feasibility and clinical impact of complying with national consensus recommendations on perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and noncardiac surgery. BACKGROUND: There are limited evidence based recommendations on the perioperative management of antiplatelet therapy in stented patients undergoing surgery. METHODS: The recommendations provided by the national consensus document were applied in a multicenter, prospective registry of consecutive patients with prior coronary stenting undergoing any type of surgery at 19 hospitals in Italy. The primary end-point was in-hospital net adverse clinical events (NACE) represented by the composite of all-cause death, myocardial infarction, probable/definite stent thrombosis and Bleeding Academic Research Consortium (BARC) grade >=3 bleeding. Patients were followed for 30 days. RESULTS: A total of 1,082 patients were enrolled. Adherence to consensus recommendations occurred in 85% of the cases. Perioperative aspirin and dual antiplatelet therapy were maintained in 69.7 and 10.5% of the cases, respectively. In-hospital NACE rate was 12.7%, being significantly higher in patients undergoing cardiac surgery (36.3% vs. 7.3%, P < 0.01), mainly due to BARC 3 bleeding events (32.3%). At 30 days, MACE rates were similar (3.5% vs. 3.5%, P = NS) in patients undergoing cardiac and noncardiac surgery, whereas BARC >=3 bleeding events were significantly higher with cardiac surgery (36.3% vs. 5.6%, P < 0.01). CONCLUSIONS: The results of this registry demonstrate the safety and feasibility of applying a national consensus document on the perioperative management of antiplatelet therapy in stented patients undergoing surgery. (c) 2016 Wiley Periodicals, Inc. PMID- 27404799 TI - Sox transcription in sarcosine utilization is controlled by Sigma(54) and SoxR in Bacillus thuringiensis HD73. AB - Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde, and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical -12/-24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma(54) factor and is activated by the Sigma(54)-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma(54)-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization. PMID- 27404798 TI - Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis. AB - Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders. PMID- 27404800 TI - Modelling of Yeast Mating Reveals Robustness Strategies for Cell-Cell Interactions. AB - Mating of budding yeast cells is a model system for studying cell-cell interactions. Haploid yeast cells secrete mating pheromones that are sensed by the partner which responds by growing a mating projection toward the source. The two projections meet and fuse to form the diploid. Successful mating relies on precise coordination of dynamic extracellular signals, signaling pathways, and cell shape changes in a noisy background. It remains elusive how cells mate accurately and efficiently in a natural multi-cell environment. Here we present the first stochastic model of multiple mating cells whose morphologies are driven by pheromone gradients and intracellular signals. Our novel computational framework encompassed a moving boundary method for modeling both a-cells and alpha-cells and their cell shape changes, the extracellular diffusion of mating pheromones dynamically coupled with cell polarization, and both external and internal noise. Quantification of mating efficiency was developed and tested for different model parameters. Computer simulations revealed important robustness strategies for mating in the presence of noise. These strategies included the polarized secretion of pheromone, the presence of the alpha-factor protease Bar1, and the regulation of sensing sensitivity; all were consistent with data in the literature. In addition, we investigated mating discrimination, the ability of an a-cell to distinguish between alpha-cells either making or not making alpha factor, and mating competition, in which multiple a-cells compete to mate with one alpha-cell. Our simulations were consistent with previous experimental results. Moreover, we performed a combination of simulations and experiments to estimate the diffusion rate of the pheromone a-factor. In summary, we constructed a framework for simulating yeast mating with multiple cells in a noisy environment, and used this framework to reproduce mating behaviors and to identify strategies for robust cell-cell interactions. PMID- 27404801 TI - Joint effects of folate intake and one-carbon-metabolizing genetic polymorphisms on breast cancer risk: a case-control study in China. AB - This study aimed to examine the joint effects of folate intake, polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTRR) and methionine synthase (MTR) genes and breast cancer risk. A case-control study of 570 consecutively recruited breast cancer cases and 576 controls was conducted in Guangzhou, China. Multifactor dimensionality reduction and logistic regression approach were used to evaluate gene-gene interaction. The covariates were chosen based on comparison of baseline characteristics of cases and controls. Folate intake was found to be inversely associated with breast cancer risk. The MTRRrs162036 GG genotype was associated with a decreased risk of breast cancer [adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20-0.85]. Compared with the wild-type group (MTRRrs162036 AA with MTRrs1805087 AA) MTRRrs162036 AA with MTRrs1805087 GA + GG was associated with a decreased risk (OR 0.70, 95% CI 0.48-1.03). With the combined MTHFRrs1801131 TT and MTHFRrs1801133 GG genotypes as a reference, MTHFRrs1801131 TT with MTHFRrs1801133 GA + AA was associated with a decreased risk (OR 0.78, 95% CI 0.57 - 1.08) and MTHFRrs1801131 GT + GG with MTHFRrs1801133 GA + AA was associated with an increased risk (OR 1.35, 95% CI 0.88-2.05). The joint impact of MTRRrs162036 and MTRrs1805087, MTHFRrs1801131 and MTHFRrs1801133, folate and MTHFRrs1801133 may contribute to breast cancer risk. PMID- 27404802 TI - Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice. AB - Regulatory T (Treg) cells, which express Foxp3 as a transcription factor, are subsets of CD4(+) T cells. Treg cells play crucial roles in immune tolerance and homeostasis maintenance by regulating the immune response. The primary role of Treg cells is to suppress the proliferation of effector T (Teff) cells and the production of cytokines such as IFN-gamma, TNF-alpha, and IL-2. It has been demonstrated that Treg cells' ability to inhibit the function of Teff cells is enhanced during persistent pathogen infection and cancer development. To clarify the function of Treg cells under resting or inflamed conditions, a variety of in vitro suppression assays using mouse or human Treg cells have been devised. The main aim of this study is to develop a method to compare the differences in phenotype and suppressive function between resting and activated Treg cells. To isolate activated Treg cells, mice were infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13), a chronic strain of LCMV. Treg cells isolated from the spleen of LCMV CL13-infected mice exhibited both the activated phenotype and enhanced suppressive activity compared with resting Treg cells isolated from naive mice. Here, we describe the basic protocol for ex vivo phenotype analysis to distinguish activated Treg cells from resting Treg cells. Furthermore, we describe a protocol for the measurement of the suppressive activity of fully activated Treg cells. PMID- 27404803 TI - A novel profile/view ordering with a non-convex star shutter for high-resolution 3D volumetric T1 mapping under multiple breath-holds. AB - PURPOSE: To examine a novel non-convex star ordering/shutter for reducing the number of breath-holds in cardiac three-dimensional (3D) T1 Mapping MRI with multiple breath-holds. METHODS: A novel ordering, Non-Convex Star (NCS) was designed to acquire 3D volumes in a modified look-locker inversion recovery (MOLLI) T1 mapping sequence to provide more spatial resolution and coverage in fewer breath-holds. The proposed 3D-MOLLI approach using NCS was first validated in two phantoms using artifact power (AP) measurement against the fully sampled phantom. This was followed by an in vivo study in seven swine, in which the T1 values of the left ventricular (LV) myocardium divided into the American Heart Association (AHA) 16-segment model was compared against the reference multislice two-dimensional (2D) clinical reference and 3D volume without NCS breath-hold reduction. RESULTS: NCS breath-hold reduction yielded less AP compared with the matched SENSE accelerated phantom volume (P < 0.0005), and was shown to be optimal at 25% fewer breath-holds. Calculated T1 values from 3D in vivo volumes with/without NCS were comparable in all AHA segments (P = NS), whereas 3D-NCS yielded significantly higher T1 values than 2D at midslice of the LV myocardium in each AHA segment (P < 0.05). CONCLUSION: We successfully demonstrate the feasibility of the NCS approach for a 3D T1 mapping acquisition requiring fewer breath-holds. Magn Reson Med 77:2215-2224, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27404804 TI - The role of color and attention-to-color in mirror-symmetry perception. AB - The role of color in the visual perception of mirror-symmetry is controversial. Some reports support the existence of color-selective mirror-symmetry channels, others that mirror-symmetry perception is merely sensitive to color-correlations across the symmetry axis. Here we test between the two ideas. Stimuli consisted of colored Gaussian-blobs arranged either mirror-symmetrically or quasi-randomly. We used four arrangements: (1) 'segregated' - symmetric blobs were of one color, random blobs of the other color(s); (2) 'random-segregated' - as above but with the symmetric color randomly selected on each trial; (3) 'non-segregated' - symmetric blobs were of all colors in equal proportions, as were the random blobs; (4) 'anti-symmetric' - symmetric blobs were of opposite-color across the symmetry axis. We found: (a) near-chance levels for the anti-symmetric condition, suggesting that symmetry perception is sensitive to color-correlations across the symmetry axis; (b) similar performance for random-segregated and non-segregated conditions, giving no support to the idea that mirror-symmetry is color selective; (c) highest performance for the color-segregated condition, but only when the observer knew beforehand the symmetry color, suggesting that symmetry detection benefits from color-based attention. We conclude that mirror-symmetry detection mechanisms, while sensitive to color-correlations across the symmetry axis and subject to the benefits of attention-to-color, are not color selective. PMID- 27404805 TI - Synthesis and Characterization of a Tetrapodal NO4(4-) Ligand and Its Transition Metal Complexes. AB - We present the synthesis and characterization of alkali metal salts of the new tetraanionic, tetrapodal ligand 2,2'-(pyridine-2,6-diyl)bis(2-methylmalonate) (A4[PY(CO2)4], A = Li(+), Na(+), K(+), and Cs(+)), via deprotection of the neutral tetrapodal ligand tetraethyl 2,2'-(pyridine-2,6-diyl)bis(2 methylmalonate) (PY(CO2Et)4). The [PY(CO2)4](4-) ligand is composed of an axial pyridine and four equatorial carboxylate groups and must be kept at or below 0 degrees C to prevent decomposition. Exposing it to a number of divalent first-row transition metals cleanly forms complexes to give the series K2[(PY(CO2)4)M(H2O)] (M = Mn(2+), Fe(2+), Co(2+), Ni(2+), Zn(2+)). The metal complexes were comprehensively characterized via single-crystal X-ray diffraction, (1)H NMR and UV-vis absorption spectroscopy, and cyclic voltammetry. Crystal structures reveal that [PY(CO2)4](4-) coordinates in a pentadentate fashion to allow for a nearly ideal octahedral coordination geometry upon binding an exogenous water ligand. Additionally, depending on the nature of the charge-balancing countercation (Li(+), Na(+), or K(+)), the [(PY(CO2)4)M(H2O)](2-) complexes can assemble in the solid state to form one-dimensional channels filled with water molecules. Aqueous electrochemistry performed on [(PY(CO2)4)M(H2O)](2-) suggested accessible trivalent oxidation states for the Fe, Co, and Ni complexes, and the trivalent Co(3+) species [(PY(CO2)4)Co(OH)](2-) could be isolated via chemical oxidation. The successful synthesis of the [PY(CO2)4](4-) ligand and its transition metal complexes illustrates the still-untapped versatility within the tetrapodal ligand family, which may yet hold promise for the isolation of more reactive and higher valent metal complexes. PMID- 27404806 TI - Structural and Functional Investigation of FdhC from Acinetobacter nosocomialis: A Sugar N-Acyltransferase Belonging to the GNAT Superfamily. AB - Enzymes belonging to the GNAT superfamily are widely distributed in nature where they play key roles in the transfer of acyl groups from acyl-CoAs to primary amine acceptors. The amine acceptors run the gamut from histones to aminoglycoside antibiotics to small molecules such as serotonin. Whereas those family members that function on histones have been extensively studied, the GNAT enzymes that employ nucleotide-linked sugars as their substrates have not been well characterized. Indeed, though the structures of two of these "amino sugar" GNAT enzymes have been determined within the past 10 years, details concerning their active site architectures have been limited because of a lack of bound nucleotide-linked sugar substrates. Here we describe a combined structural and biochemical analysis of FdhC from Acinetobacter nosocomialis O2. On the basis of bioinformatics, it was postulated that FdhC catalyzes the transfer of a 3 hydroxybutanoyl group from 3-hydroxylbutanoyl-CoA to dTDP-3-amino-3,6-dideoxy-d galactose, to yield an unusual sugar that is ultimately incorporated into the surface polysaccharides of the bacterium. We present data confirming this activity. In addition, the structures of two ternary complexes of FdhC, in the presence of CoA and either 3-hydroxybutanoylamino-3,6-dideoxy-d-galactose or 3 hydroxybutanoylamino-3,6-dideoxy-d-glucose, were solved by X-ray crystallographic analyses to high resolution. Kinetic parameters were determined, and activity assays demonstrated that FdhC can also utilize acetyl-CoA, 3-methylcrotonyl-CoA, or hexanoyl-CoA as acyl donors, albeit at reduced rates. Site-directed mutagenesis experiments were conducted to probe the catalytic mechanism of FdhC. Taken together, the data presented herein provide significantly new molecular insight into those GNAT superfamily members that function on nucleotide-linked amino sugars. PMID- 27404807 TI - Improving mental health service responses to domestic violence and abuse. AB - Domestic violence and abuse is a considerable international public health problem, which is associated with mental disorders in both women and men. Nevertheless, victimization and perpetration remain undetected by mental health services. This paper reviews the evidence on mental health service responses to domestic violence, including identifying, referring, and providing care for people experiencing or perpetrating violence. The review highlights the need for mental health services to improve rates of identification and responses to domestic violence and abuse, through the provision of specific training on domestic violence and abuse, the implementation of clear information sharing protocols and evidence-based interventions, and the establishment of care referral pathways. This review also highlights the need for further research into mental health service users who perpetrate domestic violence and abuse. PMID- 27404819 TI - Coming in sportsmedicine. PMID- 27404817 TI - Comparing Drug Images and Repurposing Drugs with BioGPS and FLAPdock: The Thymidylate Synthase Case. AB - Repurposing and repositioning drugs has become a frequently pursued and successful strategy in the current era, as new chemical entities are increasingly difficult to find and get approved. Herein we report an integrated BioGPS/FLAPdock pipeline for rapid and effective off-target identification and drug repurposing. Our method is based on the structural and chemical properties of protein binding sites, that is, the ligand image, encoded in the GRID molecular interaction fields (MIFs). Protein similarity is disclosed through the BioGPS algorithm by measuring the pockets' overlap according to which pockets are clustered. Co-crystallized and known ligands can be cross-docked among similar targets, selected for subsequent in vitro binding experiments, and possibly improved for inhibitory potency. We used human thymidylate synthase (TS) as a test case and searched the entire RCSB Protein Data Bank (PDB) for similar target pockets. We chose casein kinase IIalpha as a control and tested a series of its inhibitors against the TS template. Ellagic acid and apigenin were identified as TS inhibitors, and various flavonoids were selected and synthesized in a second round selection. The compounds were demonstrated to be active in the low micromolar range. PMID- 27404818 TI - Three Subjects in Search of a Reader. PMID- 27404808 TI - The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. AB - New antibacterial compounds, preferentially exploiting novel cellular targets, are urgently needed to fight the increasing resistance of pathogens against conventional antibiotics. Here we demonstrate that Carolacton, a myxobacterial secondary metabolite previously shown to damage Streptococcus mutans biofilms, inhibits planktonic growth of Streptococcus pneumoniae TIGR4 and multidrug resistant clinical isolates of serotype 19A at nanomolar concentrations. A Carolacton diastereomer is inactive in both streptococci, indicating a highly specific interaction with a conserved cellular target. S. mutans requires the eukaryotic-like serine/threonine protein kinase PknB and the cysteine metabolism regulator CysR for susceptibility to Carolacton, whereas their homologues are not needed in S. pneumoniae, suggesting a specific function for S. mutans biofilms only. A bactericidal effect of Carolacton was observed for S. pneumoniae TIGR4, with a reduction of cell numbers by 3 log units. The clinical pneumonia isolate Sp49 showed immediate growth arrest and cell lysis, suggesting a bacteriolytic effect of Carolacton. Carolacton treatment caused a reduction in membrane potential, but not membrane integrity, and transcriptome analysis revealed compensatory reactions of the cell. Our data show that Carolacton might have potential for treating pneumococcal infections. PMID- 27404821 TI - Scanning sports. PMID- 27404820 TI - Noteworthy. PMID- 27404824 TI - Sportsmedicine forum. PMID- 27404825 TI - Exercise and Sudden Death. PMID- 27404826 TI - Playing the Aging Game. PMID- 27404828 TI - Special Problems of Handicapped Skiers: An Overview. AB - In brief: Skiing has become an increasingly popular sport for disabled persons over the past ten years. Special skiing programs are available throughout the United States for people of all ages with various disabilities. Disabled skiers encounter particular problems that are associated with the interaction between the environment and the effects of their specific disability. This paper discusses those problems, the basic requirements handicapped people must meet to successfully participate in these skiing programs, and the benefits of skiing for individuals with particular disabilities. These individuals include amputees, blind or deaf skiers, and skiers with neuromuscular disorders or spinal cord injuries. PMID- 27404829 TI - Cross-Country Runner With Pain in the Dorsum of the Foot. AB - A group of experts met to discuss a case from the Cleveland Clinic Foundation. This case conference is part of a series featuring a variety of sports medicine topics. PMID- 27404830 TI - Ice Hockey Injuries. AB - In brief: Ice hockey injuries can range from simple cuts and bruises to devastating spinal cord damage. The use of face protection drastically reduces the number and severity of facial and eye injuries. Professional hockey players seem to incur the most injuries (3.0 per player per year), while players in youth hockey incur the fewest (0.02 per player per year). Most injuries can be treated on the sidelines, but in most cases prevention is the key to staying in the game. The authors describe the mechanisms, management, and prevention of each type of injury. PMID- 27404831 TI - Signs, Symptoms, and Management of Jellyfish Envenomation. AB - In brief: Millions of divers, swimmers, and other ocean-goers may encounter jellyfish. If they are stung, they may need either first aid if the case is mild, or extensive treatment if they suffer anaphylaxis, cardiorespiratory problems, or long-term reactions. Some severe cases may even be fatal. The author describes the mechanisms of envenomation and tissue reaction and discusses how to recognize and treat both the immediate and late sequelae. PMID- 27404832 TI - Aerobic Requirements for and Heart Rate Responses to Variations in Rope Jumping Techniques. AB - In brief: Previous studies have suggested that experienced rope jumpers have a reduced aerobic requirement. However, these exercisers typically train with a variety of techniques, which may affect aerobic requirements. In this study, nine experienced rope jumpers performed each of five basic techniques at the same speed. Results show that the "alternate foot" technique is the most efficient; the "crossover" technique, least efficient. A subgroup of four subjects was studied to determine if they consistently trained in the aerobic range during a "typical" workout. These results show that even highly skilled rope jumpers can maintain an adequate exercise intensity during their workouts. PMID- 27404833 TI - Child and Adolescent Athletes With Diabetes. AB - In brief: The common desire to participate in sports can be harnessed to encourage children and adolescents with type 1 diabetes to participate actively in controlling their disease. This is partly because the diabetic who successfully learns to control blood glucose during exercise by wise regulation of diet and insulin is rewarded with enhanced athletic performance. Age, duration of the diabetes, insulin dosage, hypoglycemia, seasonality, training, duration of training periods, and calorie intake must be considered in prescribing specific exercise regimens for diabetic youngsters. To participate in endurance sports, persons with diabetes must manage the effects of exogenous insulin on their normal triphasic metabolic fuel supply derived from muscle, liver, and adipose tissue. If educational guidelines are followed and potential risks due to complications are taken into account, the benefits of regular exercise early in the course of the disease outweigh potential disadvantages. PMID- 27404834 TI - Acute Glycemic Effects of Exercise in Adolescents with Insulin-Dependent Diabetes Mellitus. AB - In brief: The acute effect of exercise on blood glucose was observed on 130 occasions in eight adolescents with insulin-dependent diabetes mellitus. All subjects engaged in 30 minutes of either structured aerobic exercise or unstructured recreational activity. The magnitude of decline in the blood glucose level with exercise corresponded to the preexercise blood glucose value: Higher preexercise values were associated with larger declines, while nonelevated preexercise values were associated with smaller declines. No significant differences in glycemic effect were observed between the two categories of exercise. The authors conclude that in adolescents with moderately well controlled diabetes, recreational activities can be as effective in lowering elevated blood glucose levels as structured exercise. PMID- 27404835 TI - Resistance Training: Basic Principles (Part 1 of 4). AB - In brief: This article introduces terms and concepts associated with resistance training in order to reduce the existing confusion in this area. The authors describe the sports associated with resistance training-weight lifting, power lifting, and bodybuilding-and discuss the benefits of exercising with free weights vs resistance training machines. They also make recommendations for individuals who are starting a resistance training program. PMID- 27404836 TI - Human Growth Hormone: The Latest Ergogenic Aid? AB - The supply of human growth hormone now available to athletes seems small and costly, but drug testing experts agree that abuse of the substance could become a serious problem, especially if synthetic hormone becomes more widely available. PMID- 27404837 TI - Synthetic Human Growth Hormone: A Call for Federal Control. AB - The author argues that synthetic human growth hormone is likely to be abused by athletes, and concludes that congressional action is necessary to prevent widespread abuse. PMID- 27404839 TI - Spectator Violence at Sports Events: What Keeps Enthusiastic Fans in Bounds? AB - A large crowd of fiercely loyal fans, a heated contest, and a few too many beers are a volatile mix. Sports officials must consider that mix to prevent violence related injuries among spectators. PMID- 27404838 TI - Medical Coverage of Sports Events: The Fans Need Attention, Too. AB - When an emergency occurs somewhere in the bleachers of a crowded stadium, the medical team faces a logistic challenge. Communication and transportation are key elements in effective coverage. PMID- 27404840 TI - Plyometrics: A Legitimate Form of Power Training? AB - More and more athletes are training with plyometric exercises, which involve explosive movements such as jumping. Proponents swear by the drills, but researchers have yet to substantiate the risks and benefits. PMID- 27404841 TI - Amino Acid Supplements: Beneficial or Risky? PMID- 27404842 TI - Casa de Campo: A Jock's Dreamland-and More. AB - At this well-rounded resort in the Dominican Republic, tennis, golf, and other sports activities abound, and there's even a medieval hilltop village honeycombed with flagstone piazzas, fountains, and flower-draped shops. PMID- 27404844 TI - Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala kindled seizures. AB - Temporal lobe epilepsy is the most common form of medically-intractable epilepsy. While seizures in TLE originate in structures such as hippocampus, amygdala, and temporal cortex, they propagate through a crucial relay: the midline/intralaminar thalamus. Prior studies have shown that pharmacological inhibition of midline thalamus attenuates limbic seizures. Here, we examined a recently developed technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), as a means of chemogenetic silencing to attenuate limbic seizures. Adult, male rats were electrically kindled from the amygdala, and injected with virus coding for inhibitory (hM4Di) DREADDs into the midline/intralaminar thalamus. When treated with the otherwise inert ligand Clozapine-N-Oxide (CNO) at doses of 2.5, 5, and 10mg/kg, electrographic and behavioral seizure manifestations were suppressed in comparison to vehicle. At higher doses, we found complete blockade of seizure activity in a subset of subjects. CNO displayed a sharp time-response profile, with significant seizure attenuation seen 20-30min post injection, in comparison to 10 and 40min post injection. Seizures in animals injected with a control vector (i.e., no DREADD) were unaffected by CNO administration. These data underscore the crucial role of the midline/intralaminar thalamus in the propagation of seizures, specifically in the amygdala kindling model, and provide validation of chemogenetic silencing of limbic seizures. PMID- 27404845 TI - Non-restraining EEG Radiotelemetry: Epidural and Deep Intracerebral Stereotaxic EEG Electrode Placement. AB - Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies. This powerful technique does not only provide valuable insights into the underlying pathophysiological mechanisms, i.e., the etiopathogenesis of CNS related diseases, it also facilitates the development of new translational, i.e., therapeutic approaches. Whereas competing techniques that make use of recorder systems used in jackets or tethered systems suffer from their unphysiological restraining to semi restraining character, radiotelemetric EEG recordings overcome these disadvantages. Technically, implantable EEG radiotelemetry allows for precise and highly sensitive measurement of epidural and deep, intracerebral EEGs under various physiological and pathophysiological conditions. First, we present a detailed protocol of a straight forward, successful, quick and efficient technique for epidural (surface) EEG recordings resulting in high-quality electrocorticograms. Second, we demonstrate how to implant deep, intracerebral EEG electrodes, e.g., in the hippocampus (electrohippocampogram). For both approaches, a computerized 3D stereotaxic electrode implantation system is used. The radiofrequency transmitter itself is implanted into a subcutaneous pouch in both mice and rats. Special attention also has to be paid to pre-, peri- and postoperative treatment of the experimental animals. Preoperative preparation of mice and rats, suitable anesthesia as well as postoperative treatment and pain management are described in detail. PMID- 27404846 TI - Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson's disease. AB - Type-1 interferons (IFNs) are pleiotropic cytokines with a critical role in the initiation and regulation of the pro-inflammatory response. However, the contribution of the type-1 IFNs to CNS disorders, specifically chronic neuropathologies such as Parkinson's disease is still unknown. Here, we report increased type-1 IFN signaling in both post mortem human Parkinson's disease samples and in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model. In response to MPTP, mice lacking the type-1 IFN receptor (IFNAR1(-/-) ) displayed decreased type-1 IFN signaling, an attenuated pro-inflammatory response and reduced loss of dopaminergic neurons. The neuroprotective potential of targeting the type-1 IFN pathway was confirmed by reduced neuroinflammation and DA cell death in mice treated with a blocking monoclonal IFNAR1 (MAR-1) antibody. The MPTP/MAR-1 treated mice also displayed increased striatal dopamine levels and improved behavioural outcomes compared to their MPTP/IgG controls. These data, implicate for the first time, a deleterious role for the type-1 IFNs as key modulators of the early neuroinflammatory response and therefore the neuronal cell death in Parkinson's disease. GLIA 2016;64:1590-1604. PMID- 27404847 TI - Azulenylcarbenes: Rearrangements on the C11 H8 Potential Energy Surface. AB - Four isomeric azulenylcarbenes were synthesized in argon matrices by photolysis of the corresponding diazo precursors, and the photochemistry of these carbenes was studied. The carbenes and their rearranged products were characterized by IR, UV/Vis, and EPR spectroscopy, and the experimental data were compared to results from DFT calculations. While 2-, 5- and 6-azulenylcarbene show triplet ground states, 1-azulenylcarbene exhibits a singlet ground state, in accord with theoretical predictions. The rearrangements of the azulenylcarbenes give access to a number of unusual C11 H8 isomers, such as other carbenes and strained allenes. PMID- 27404848 TI - A case-based reasoning view of thrombophilia risk. AB - Thrombophilia stands for a genetic or an acquired tendency to hypercoagulable states that increase the risk of venous and arterial thromboses. Indeed, venous thromboembolism is often a chronic illness, mainly in deep venous thrombosis and pulmonary embolism, requiring lifelong prevention strategies. Therefore, it is crucial to identify the cause of the disease, the most appropriate treatment, the length of treatment or prevent a thrombotic recurrence. Thus, this work will focus on the development of a diagnosis decision support system in terms of a formal agenda built on a logic programming approach to knowledge representation and reasoning, complemented with a case-based approach to computing. The proposed model has been quite accurate in the assessment of thrombophilia predisposition risk, since the overall accuracy is higher than 90% and sensitivity ranging in the interval [86.5%, 88.1%]. The main strength of the proposed solution is the ability to deal explicitly with incomplete, unknown, or even self-contradictory information. PMID- 27404849 TI - Detecting the presence of an indwelling urinary catheter and urinary symptoms in hospitalized patients using natural language processing. AB - OBJECTIVE: To develop a natural language processing pipeline to extract positively asserted concepts related to the presence of an indwelling urinary catheter in hospitalized patients from the free text of the electronic medical note. The goal is to assist infection preventionists and other healthcare professionals in determining whether a patient has an indwelling urinary catheter when a catheter-associated urinary tract infection is suspected. Currently, data on indwelling urinary catheters is not consistently captured in the electronic medical record in structured format and thus cannot be reliably extracted for clinical and research purposes. MATERIALS AND METHODS: We developed a lexicon of terms related to indwelling urinary catheters and urinary symptoms based on domain knowledge, prior experience in the field, and review of medical notes. A reference standard of 1595 randomly selected documents from inpatient admissions was annotated by human reviewers to identify all positively and negatively asserted concepts related to indwelling urinary catheters. We trained a natural language processing pipeline based on the V3NLP framework using 1050 documents and tested on 545 documents to determine agreement with the human reference standard. Metrics reported are positive predictive value and recall. RESULTS: The lexicon contained 590 terms related to the presence of an indwelling urinary catheter in various categories including insertion, care, change, and removal of urinary catheters and 67 terms for urinary symptoms. Nursing notes were the most frequent inpatient note titles in the reference standard document corpus; these also yielded the highest number of positively asserted concepts with respect to urinary catheters. Comparing the performance of the natural language processing pipeline against the human reference standard, the overall recall was 75% and positive predictive value was 99% on the training set; on the testing set, the recall was 72% and positive predictive value was 98%. The performance on extracting urinary symptoms (including fever) was high with recall and precision greater than 90%. CONCLUSIONS: We have shown that it is possible to identify the presence of an indwelling urinary catheter and urinary symptoms from the free text of electronic medical notes from inpatients using natural language processing. These are two key steps in developing automated protocols to assist humans in large-scale review of patient charts for catheter-associated urinary tract infection. The challenges associated with extracting indwelling urinary catheter-related concepts also inform the design of electronic medical record templates to reliably and consistently capture data on indwelling urinary catheters. PMID- 27404850 TI - What is the Best Treatment for a Thoracolumbar Burst Fracture in a Neurologically Intact Patient in the Absence of Posterior Ligamentous Disruption: Surgical Treatment. PMID- 27404851 TI - Failure to Launch: What the Rejection of Lumbar Total Disk Replacement Tells us About American Spine Surgery. AB - STUDY DESIGN: Spine surgeon survey. OBJECTIVE: The objective was to investigate the failure of widespread adoption of lumbar total disk replacement (L-TDR) in the United States. SUMMARY OF BACKGROUND DATA: L-TDR has been available for use in the United States since 2005. L-TDR has not gained wide acceptance as a treatment for degenerative disk disease despite substantial investments in product development and positive results in randomized controlled trials. METHODS: Estimates of the number of L-TDR procedures performed in the United States from 2005 to 2010 were calculated using the Nationwide Inpatient Sample database. Insurance policies were assessed for L-TDR coverage through Internet search. Finally, an 18-question survey regarding surgeons' opinions toward L-TDR was distributed to the members of North American Spine Society. RESULTS: The estimated number of primary L-TDR procedures performed in the United States decreased from 3650 in 2005 to 1863 in 2010, whereas revision L-TDR procedures increased from 420 to 499. Of 14 major insurers, 11 (78.6%) do not cover L-TDR. In total, 613 spine surgeons responded to the survey. Over half of respondents (51.1%, 313/612) have performed L-TDR, although only 44.6% (136/305) of initial adopters currently perform the surgery. However, 81.5% (106/130) of those currently performing L-TDR have been satisfied with the results. When asked about their perceptions of L-TDR, 65.0% (367/565) indicated a lack of insurance coverage for L-TDR in their region, 54.9% (310/565) worry about long-term complications, and 52.7% (298/565) worry about the technical challenges of revision. CONCLUSIONS: Despite early enthusiasm for L-TDR, wide adoption has not occurred. A primary reason for this failure seems to be a lack of insurance coverage, despite intermediate-term clinical success. In addition, surgeons continue to express concerns regarding long-term outcomes and the technical difficulties of revision. This case study of a failed surgical innovation may signal increasing involvement of payers in clinical decision-making and may be instructive to surgeons, policymakers, and manufacturers. PMID- 27404852 TI - Current Trends in Outpatient Spine Surgery. AB - Because of the increasing pressure to contain health-care-related costs, the number of spinal surgeries performed in the outpatient setting has significantly increased. The higher perioperative efficiency and greater predictability of associated costs offer significant incentives for payers and providers to move surgical procedures into the outpatient setting. Nonetheless, judicious patient selection is advised to optimize outcomes. PMID- 27404853 TI - Unilateral Versus Bilateral Pedicle Screw Fixation in Transforaminal Lumbar Interbody Fusion: A Monocentric Study of 215 Patients With a Minimum of 4-Year Follow-up. AB - STUDY DESIGN: A retrospective clinical study. OBJECTIVE: This study sought to retrospectively compare the mid-term to long-term outcomes between unilateral pedicle screw (UPS) and bilateral pedicle screw (BPS) augmented transforaminal lumbar interbody fusion (TLIF) in lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA: Recently, UPS fixation has been applied in TLIF, for its satisfactory clinical outcome, less implants and less invasiveness. However, only short-term outcome has been reported, the mid-term to long-term outcome has not been well characterized. MATERIALS AND METHODS: From June 2007 to February 2011, 215 of 348 consecutive patients suffering from lumbar degenerative diseases were operated in our hospital and accomplished a minimum of 4-year follow-up. These patients were divided into 2 groups according to the operative techniques: UPS group (n=109), and bilateral pedicle screw group (n=106). Operative time, blood loss, length of hospital stay, hospital bill, fusion status, and complications were recorded and analyzed statistically. Visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores were used to assess the preoperative and postoperative pain and functional outcome. RESULTS: The mean follow-up duration was 52.2 months. A significant decrease occurred in operative time, blood loss, and hospital bill in unilateral group, compared with bilateral group (P<0.05). The average postoperative visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores improved significantly in each group than the preoperative counterparts (P<0.05); however, there were no significant difference between groups at any follow-up time point (P>0.05). No statistically difference was detected regarding fusion rate and complication rate between the 2 groups (P>0.05), except the cage migration rate (P<0.05). CONCLUSIONS: UPS fixation could achieve satisfactory clinical outcome similar to bilateral fixation in TLIF at a mid-term to long-term follow-up. To avoid cage migration, bullet-shaped cages should not be used in the unilateral group. PMID- 27404854 TI - All-Pedicle Screw Fixation With 6-mm-Diameter Cobalt-Chromium Rods Provides Optimized Sagittal Correction of Adolescent Idiopathic Scoliosis. AB - PURPOSE: Recently introduced cobalt-chromium (CoCr) rods that rely solely on pedicle screws produce very good results in correcting scoliotic curves. All pedicle screws constructs are also suspected of decreasing thoracic kyphosis. The current study was designed to evaluate sagittal correction in adolescent idiopathic scoliosis patients, using 6-mm CoCr rods and all-screw constructs. MATERIALS AND METHODS: A total of 61 patients treated by posterior spinal fusion and instrumentation, using all-pedicle screw constructs were included. The mean age at surgery was 15.4 years (range, 12-18 y). Forty-five patients (group A) were diagnosed with decreased thoracic kyphosis, and 16 patients (group B) had normal (35-50 degrees) thoracic kyphosis. RESULTS: The preoperative main Cobb angle was 62.93+/-19.38 degrees in group A and 73.45+/-22.13 degrees in group B. In group A, the postoperative main Cobb angle was 23.33+/-12.71 degrees. In group B, the postoperative main Cobb angle was 27.20+/-10.04 degrees. The T4-T12 thoracic kyphosis improved postoperatively from 18.15+/-10.29 to 28.18+/-8.35 degrees in group A. In group B, the postoperative T4-T12 thoracic kyphosis was 40.34+/-3.13 degrees. Statistical analysis showed a significant improvement between preoperative and postoperative values of T4-T12 thoracic kyphosis in group A. In group B, the differences in T4-T12 thoracic kyphosis values were not statistically significant. CONCLUSIONS: Our result demonstrates a significant improvement of T4-T12 thoracic kyphosis in the hypokyphotic group of patients and confirms that CoCr rods can produce sagittal corrections in hypokyphotic adolescent idiopathic scoliosis patients. Our results confirm the benefit of combining all-pedicle screw constructs with a posterolateral translational in situ bending procedure to correct hypokyphosis directly. PMID- 27404855 TI - The Significance of the Tromner Sign in Cervical Spondylotic Myelopathy Patient. AB - STUDY DESIGN: This study is a diagnostic analysis. OBJECTIVE: To investigate the diagnostic accuracy of Tromner sign in cervical spondylotic myelopathy (CSM), and how its presence correlates with the severity of myelopathy. SUMMARY OF BACKGROUND DATA: A clinical presentation of myelopathy corresponding with image findings is a current standard to diagnose CSM. Tromner sign is an alternative of well-known Hoffmann sign to detect CSM. Little is known about its diagnostic accuracy and how its presence correlates with the severity of CSM. MATERIALS AND METHODS: Consecutive patients with clinical diagnosis of CSM and other cervical spondylosis-related problems were enrolled in either CSM group, cervical spondylotic radiculopathy group, or axial pain group. Normal volunteers and patients without spine-related issues were used as a control. All participants were examined for the presence of myelopathic signs. Magnetic resonance imaging studies of all participants were reviewed by a radiologist. RESULTS: There were 85 participants included in the study. Diagnostic sensitivity was 76%, 94%, 76%, and 36% for Hoffmann sign, Tromner sign, inverted radial reflex, and Babinski sign, respectively. Tromner sign had relatively high sensitivity (95%) despite of mild degree of myelopathy. Negative predictive value was 60%, 85%, 59%, and 38% for Hoffmann sign, Tromner sign, inverted radial reflex, and Babinski sign, respectively. There were 63%-71% of patients in either axial pain group or cervical spondylotic radiculopathy group had positive Tromner sign. Most of CSM patients with cord signal changed had positive myelopathic sign. Regarding CSM patient without cord signal change, most of tests were negative except Tromner sign. CONCLUSIONS: High sensitivity (94%) and relatively high negative predictive value (85%) for Tromner sign indicate the usefulness of Tromner sign in ruling out CSM. High incidence of positive Tromner sign in presymptomatic cervical cord compression patients suggests Tromner sign could have a useful role in early detection of presymptomatic patients. PMID- 27404856 TI - Intraoperative Use of Neuromonitoring in Multilevel Thoracolumbar Spine Instrumentation and the Effects on Postoperative Neurological Injuries. AB - STUDY DESIGN: Retrospective cohort analysis of a national database between 2005 and 2011. OBJECTIVE: To investigate the current usage of neuromonitoring in patients undergoing multilevel thoracolumbar spine surgery. We hypothesize that the use of neuromonitoring would be associated with a reduced incidence of postoperative neurological injuries. SUMMARY OF BACKGROUND DATA: Intraoperative neuromonitoring is a common technique utilized in spine surgery to improve safety and reduce neurological injuries. However, the literature remains unclear in defining the populations that benefit from the use of neuromonitoring. METHODS: The PearlDiver Medicare database was queried to identify patients undergoing multilevel thoracolumbar spine instrumentation (defined as >3 thoracolumbar levels) from 2005 to 2011. The use of neuromonitoring was identified by Current Procedural Terminology codes. Neurological injuries were identified by codes from the International Classification of Diseases, Ninth Revision. RESULTS: Within 15,032 patients, the postoperative rate of neurological injury diagnosis was higher when neuromonitoring was used at both 1 week (1.3% vs. 1.0%, P=0.06) and 6 months (5.9% vs. 4.6%, P=0.0005). However, a lower incidence of neurological injury was associated with neuromonitoring in patients undergoing specifically anterior fusion of 4-7 levels, posterior fusion of 7-12 levels, and in adults below 65 years old (P=0.0266, 0.0458, 0.032). CONCLUSION: Within the total Medicare cohort, the use of neuromonitoring was not associated with a decreased rate of neurological injury in multilevel thoracolumbar instrumentation procedures. This is likely due to the possible selection and detection bias of utilizing neuromonitoring when there is an increased risk of neurological injury based on patient-specific pathology and/or surgical procedure. However, despite the overall potential bias, it was appreciated that in subgroups: age below 65 years old, anterior fusion of 4-7 segments, and posterior fusion of 7-12 segments, there was a statistically significant reduction in the incidence of neurological injuries with neuromonitoring. LEVEL OF EVIDENCE: Level III. PMID- 27404857 TI - Minimally Invasive Cervical Pedicle Screw Fixation by a Posterolateral Approach for Acute Cervical Injury. AB - STUDY DESIGN: This is a retrospective case series. OBJECTIVE: To avoid lateral misplacement of midcervical pedicle screws, T.T., one of our authors, developed a method for minimally invasive cervical pedicle screw (MICEPS) fixation by a posterolateral approach. We reviewed our initial experience with this fixation for trauma cases. SUMMARY OF BACKGROUND DATA: Excellent clinical results with cervical screws have been reported for trauma cases. Although cervical pedicle screw fixation can be an essential part of reconstruction in spinal disorders, there is also a risk for injury to the vertebral artery. METHODS: This study included 56 consecutive patients who received surgery for cervical fractures. We inserted a total of 203 cervical pedicle screws. Nineteen patients were treated by conventional methods. Thirty-seven patients were treated by MICEPS fixation. According to the MICEPS fixation, 12 patients were treated by unilateral fusion, 25 patients by bilateral fusion. All pedicle screws were inserted using spinal navigation system in the both groups. RESULTS: The average surgical time was 217 minutes with the conventional pedicle screw fixation and 165 minutes with the MICEPS fixation (P=0.0014). The average intraoperative bleeding was 560 mL in the conventional fixation and 140 mL in the MICEPS fixation (P<0.0001). Clinically significant screw deviation was significantly lower in the MICEPS fixation group than in the conventional cervical pedicle screw group (P=0.0039). There was not any deep wound infection in both groups. CONCLUSIONS: This intramuscular approach allows for horizontal pedicle screw insertion. This technique is probably useful for reducing intraoperative bleeding. In this study, incidence of screw perforation was significantly lower in the MICEPS fixation group than in the conventional cervical pedicle screw group. In particular, neither of the misplaced screws was laterally deviated in the MICEPS group. PMID- 27404859 TI - Rewriting our future. PMID- 27404860 TI - Duchenne muscular dystrophy drugs at the crossroads, as newer agents advance. PMID- 27404858 TI - Antibody Binding Specificity for Kappa (Vkappa) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study. AB - Antibodies of the IgM isotype are often neglected as potential therapeutics in human trials, animal models of human diseases as well as detecting agents in standard laboratory techniques. In contrast, several human IgMs demonstrated proof of efficacy in cancer models and models of CNS disorders including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Reasons for their lack of consideration include difficulties to express, purify and stabilize IgM antibodies, challenge to identify (non-protein) antigens, low affinity binding and fundamental knowledge gaps in carbohydrate and lipid research. This manuscript uses HIgM12 as an example to provide a detailed protocol to detect antigens by Western blotting, immunoprecipitations and immunocytochemistry. HIgM12 targets polysialic acid (PSA) attached to the neural cell adhesion molecule (NCAM). Early postnatal mouse brain tissue from wild type (WT) and NCAM knockout (KO) mice lacking the three major central nervous system (CNS) splice variants NCAM180, 140 and 120 was used to evaluate the importance of NCAM for binding to HIgM12. Further enzymatic digestion of CNS tissue and cultured CNS cells using endoneuraminidases led us to identify PSA as the specific binding epitope for HIgM12. PMID- 27404861 TI - Neural stem cell trailblazer StemCells folds. PMID- 27404862 TI - FDA snubs first smart pill. PMID- 27404863 TI - Outlook for NGF inhibitor painkiller class brightens. PMID- 27404864 TI - Mayo Clinic to share 1 million. PMID- 27404865 TI - FDA wades into sequencing-based diagnostics regulation. PMID- 27404866 TI - Biogen's once-monthly MS injection gets FDA nod. PMID- 27404868 TI - First EU PRIME designations. PMID- 27404867 TI - Stemcentrx bags $5.8 billion, even as Notch agent underwhelms. PMID- 27404870 TI - Organ delivery by 1,000 drones. PMID- 27404871 TI - The value of royalty. PMID- 27404872 TI - How China can enhance adoption of biotech crops. PMID- 27404873 TI - European incoherence on GMO cultivation versus importation. PMID- 27404874 TI - Analyzing CRISPR genome-editing experiments with CRISPResso. PMID- 27404875 TI - Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data. PMID- 27404876 TI - CrispRVariants charts the mutation spectrum of genome engineering experiments. PMID- 27404878 TI - Plant specific N-glycans do not have proven adverse effects in humans. PMID- 27404877 TI - Software tools for single-cell tracking and quantification of cellular and molecular properties. PMID- 27404879 TI - Public biotech in 2015 - the numbers. PMID- 27404881 TI - Recent patents in gene editing. PMID- 27404880 TI - Are reverse payments and pay-for-delay settlements business as usual or an anticompetitive practice? PMID- 27404882 TI - Safer conditioning for blood stem cell transplants. PMID- 27404883 TI - Tracking translation one mRNA at a time. PMID- 27404885 TI - Tracing cell lineages with mutable barcodes. PMID- 27404886 TI - Boosting the career development of postdocs with a peer-to-peer mentor circles program. PMID- 27404889 TI - Crystal Structures of the Iron-Sulfur Cluster-Dependent Quinolinate Synthase in Complex with Dihydroxyacetone Phosphate, Iminoaspartate Analogues, and Quinolinate. AB - The quinolinate synthase of prokaryotes and photosynthetic eukaryotes, NadA, contains a [4Fe-4S] cluster with unknown function. We report crystal structures of Pyrococcus horikoshii NadA in complex with dihydroxyacetone phosphate (DHAP), iminoaspartate analogues, and quinolinate. DHAP adopts a nearly planar conformation and chelates the [4Fe-4S] cluster via its keto and hydroxyl groups. The active site architecture suggests that the cluster acts as a Lewis acid in enediolate formation, like zinc in class II aldolases. The DHAP and putative iminoaspartate structures suggest a model for a condensed intermediate. The ensemble of structures suggests a two-state system, which may be exploited in early steps. PMID- 27404888 TI - GLUT1-mediated glucose uptake plays a crucial role during Plasmodium hepatic infection. AB - Intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. Here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite Plasmodium berghei and that glucose uptake via the GLUT1 transporter is specifically enhanced in P. berghei-infected cells. We further show that ATP levels of cells containing developing parasites are decreased, which is known to enhance membrane GLUT1 activity. In addition, GLUT1 molecules are translocated to the membrane of the hepatic cell, increasing glucose uptake at later stages of infection. Chemical inhibition of GLUT1 activity leads to a decrease in glucose uptake and the consequent impairment of hepatic infection, both in vitro and in vivo. Our results reveal that changes in GLUT1 conformation and cellular localization seem to be part of an adaptive host response to maintain adequate cellular nutrition and energy levels, ensuring host cell survival and supporting P. berghei hepatic development. PMID- 27404890 TI - Physiological and parasitological implications of living in a city: the case of the white-footed tamarin (Saguinus leucopus). AB - Among primates, the Neotropical Callitrichid monkeys (tamarins and marmosets) exhibit a particular ability to adapt to disturbed and urbanized environments. However, little is known about physiological and health status in contrasting ecological contexts. An example of adaptation to urban environments is the white footed tamarin (Saguinus leucopus), an endangered species endemic to the central Andes in North West Colombia. This species was used as a model to contrast physical condition, physiological parameters and the parasite community of wild populations in rural and urban settings. Overall, the tamarins seemed to be in good body condition in both environments; however, urban tamarins exhibited overweight, elevated body mass, and higher cholesterol levels, while rural tamarins showed larger diversity and prevalence of parasites. Variation in several hematological parameters associated with altitude was also observed. Our data provide preliminary evidence of differential physiological responses to urban and rural environments in tamarins. These results may be attributed to nutritional factors, physical activity, and specific parasite-host ecological interactions in these two environments. Also, abundance and diversity of the parasite community in urban environments may be potentially constrained by habitat fragmentation and relatively fewer reservoirs. Finally, significant physiological and ecological disparities between white-footed tamarins occurring in urban and rural habitats as well as physiological response to hypoxia at higher altitudes were evidenced here. This study provides important preliminary information that will be useful to determine the ability of New World primate populations to cope with urban development and rapidly changing environments. PMID- 27404891 TI - Decreased expression of Calpain-9 predicts unfavorable prognosis in patients with gastric cancer. AB - Calpain-8 and calpain-9 belong to the family of calcium-dependent cysteine proteases, which are highly expressed in the stomach. However, the roles of calpain-8 and calpain-9 in gastric tumorigenesis remain little understood. Herein, we demonstrated that calpain-9 was generally decreased in gastric cancer cell lines and primary tumor tissues, while calpain-8 expression was not significantly altered. Calpain-9, but not calpain-8, induced cell cycle arrest in the G1 phase and cellular apoptosis in vitro, and it attenuated the growth of subcutaneous tumor xenografts in vivo. Low expression of calpain-9 was positively associated with male sex, late T stage, lymph node metastasis, and advanced TNM stage. Further analysis identified calpain-9 as an independent prognostic factor for poor prognosis, and combining calpain-9 with TNM stage generated a better predictive model for patient outcomes. In conclusion, calpain-9 is a tumor suppressor that can be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer. PMID- 27404892 TI - Cutaneous Surgical Denervation: A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease. AB - Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies have suggested that nerves may also modulate skin disorders including atopic dermatitis, psoriasis and cancer. Here, we describe protocols for testing the requirement for nerves in maintaining a cutaneous mechanosensory organ, the touch dome (TD). Specifically, we discuss methods for genetically labeling, harvesting and visualizing TDs by whole-mount staining, and for performing unilateral surgical denervation on mouse dorsal back skin. Together, these approaches can be used to directly compare TD morphology and gene expression in denervated as well as sham-operated skin from the same animal. These methods can also be readily adapted to examine the requirement for nerves in mouse models of skin pathology. Finally, the ability to repeatedly sample the skin provides an opportunity to monitor disease progression at different stages and times after initiation. PMID- 27404893 TI - Otosclerosis Associated with a De Novo Mutation -832G > A in the TGFB1 Gene Promoter Causing a Decreased Expression Level. AB - Otosclerosis (OTSC) is defined by abnormal bone remodeling in the otic capsule of middle ear which leads to conductive hearing loss. In our previous study, we have identified a de novo heterozygous mutation -832G > A in the promoter of TGFB1 in an otosclerosis patient. In the present study, we progressively screened this mutation in a cohort of 254 cases and 262 controls. The family members of the patient positive for -832G > A variation were also screened and found inheritance of this variation only to her daughter. Interestingly, this variation is associated with a decreased level of the TGFB1 transcript in the patient compared to her parents and controls. In silico analysis of this mutation predicted the altered binding of two transcription factors v-Myb and MZF1 in the mutated promoter sequence. Further, functional analysis of this mutation using in vitro luciferase and electrophoretic mobility shift assays revealed that this variation is associated with decreased gene expression. In conclusion, this study established the fact that TGFB1 mutation -832G > A altered the TGFB1 promoter activity, which could affect the susceptibility to otosclerosis development. Further, systemic analysis of TGFB1 gene sequence and expression analysis of this gene might reveal its precise role in the pathogenesis of otosclerosis. PMID- 27404894 TI - Transcriptomic analysis of different stages of pigeon ovaries by RNA-sequencing. AB - The pigeon ovary is an ideal model for deciphering the molecular mechanism of folliculogenesis. While most analysis has focused on the influence of hormones and factors on ovarian follicle development in this model, changes occurring in the ovarian stroma can also be extremely informative. Here, we profiled the transcriptome of pigeon ovaries at pre-ovulation, post-ovulation, and 5-6 days after ovulation using RNA-sequencing to gain insights into the molecular and cellular events mediating ovary activity. We obtained 44,784,505 clean reads that aligned with 14,088 genes. Gene expression profile analysis identified 409 differentially expressed genes between pre- and post-ovulation; 96 genes were up regulated genes while 313 genes were down-regulated. Gene ontology analysis of the down-regulated genes revealed significant enrichment in components of the immune response, immune system, antigen processing and presentation, receptor binding, and biological adhesion. Pathway analyses of the high-expression genes of the post-ovulation ovary identified enrichment in phagosomes, lysosomes, cytokine-cytokine receptor interactions, cell adhesion molecules, and the Toll like receptor signaling. These data together suggest that post-ovulatory follicle regression and elimination occurs through an immune response. Mol. Reprod. Dev. 83: 640-648, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27404895 TI - Theoretical Analysis of the Effect of C?C Double Bonds on the Low-Temperature Reactivity of Alkenylperoxy Radicals. AB - Biodiesel contains a large proportion of unsaturated fatty acid methyl esters. Its combustion characteristics, especially its ignition behavior at low temperatures, have been greatly affected by these C?C double bonds. In this work, we performed a theoretical analysis of the effect of C?C double bonds on the low temperature reactivity of alkenylperoxy radicals, the key intermediates from the low-temperature combustion of biodiesel. To understand how double bonds affect the fate of peroxy radicals, we selected three representative peroxy radicals from heptane, heptene, and heptadiene having zero, one, and two double C?C bonds, respectively, for study. The potential energy surfaces were explored at the CBS QB3 level, and the reaction rate constants were computed using canonical/variational transition state theories. We have found that the double bond is responsible for the very different bond dissociation energies of the various types of C-H bonds, which in turn affect significantly the reaction kinetics of alkenylperoxy radicals. PMID- 27404896 TI - Prognostic variables in high-risk cutaneous squamous cell carcinoma: a review. AB - Cutaneous squamous cell carcinoma (SCC) is a growing public health problem in the United States. A subset of high-risk SCC exhibits a more aggressive clinical trajectory including increased local recurrence and lymph node metastasis. However, there are no universally accepted criteria to help define and manage these patients. This review provides an overview of the high-risk features of cutaneous SCC, prognostic stratification of various staging systems and treatment options. It further examines the prognostic factors influencing the staging of cutaneous head and neck SCC. PMID- 27404897 TI - From l-Rhamnose to Rare 6-Deoxy-l-Hexoses. AB - Efficient and rapid transformation of cheaply available l-rhamnose into all the isomeric 6-deoxy-l-hexoses via regio- and stereoselective nucleophilic displacements of triflates is reported. The synthesis entails regioselective protections, one-pot double displacements of triflates, and cascade inversions. The methodology allows facile access to all the rare 6-deoxy-l-hexoses as stable thioglycoside building blocks. PMID- 27404898 TI - Methods for Measuring the Orientation and Rotation Rate of 3D-printed Particles in Turbulence. AB - Experimental methods are presented for measuring the rotational and translational motion of anisotropic particles in turbulent fluid flows. 3D printing technology is used to fabricate particles with slender arms connected at a common center. Shapes explored are crosses (two perpendicular rods), jacks (three perpendicular rods), triads (three rods in triangular planar symmetry), and tetrads (four arms in tetrahedral symmetry). Methods for producing on the order of 10,000 fluorescently dyed particles are described. Time-resolved measurements of their orientation and solid-body rotation rate are obtained from four synchronized videos of their motion in a turbulent flow between oscillating grids with Rlambda = 91. In this relatively low-Reynolds number flow, the advected particles are small enough that they approximate ellipsoidal tracer particles. We present results of time-resolved 3D trajectories of position and orientation of the particles as well as measurements of their rotation rates. PMID- 27404899 TI - Catalytic Macrocyclization Strategies Using Continuous Flow: Formal Total Synthesis of Ivorenolide A. AB - A formal total synthesis of ivorenolide A has been accomplished employing a Z selective olefin cross metathesis and a macrocyclic Glaser-Hay coupling as key steps. The macrocyclization protocol employed a phase separation/continuous flow manifold whose advantages include catalysis, fast reaction times, high concentrations, and facile scale-up. PMID- 27404900 TI - Multiclass imbalance learning: Improving classification of pediatric brain tumors from magnetic resonance spectroscopy. AB - PURPOSE: Classification of pediatric brain tumors from 1 H-magnetic resonance spectroscopy (MRS) can aid diagnosis and management of brain tumors. However, varied incidence of the different tumor types leads to imbalanced class sizes and introduces difficulties in classifying rare tumor groups. This study assessed different imbalanced multiclass learning techniques and compared the use of complete spectra and quantified metabolite profiles for classification of three main childhood brain tumor types. METHODS: Single-voxel, Short echo time MRS data were collected from 90 patients with pilocytic astrocytoma (n = 42), medulloblastoma (n = 38), or ependymoma (n = 10). Both spectra and metabolite profiles were used to develop the learning algorithms. The borderline synthetic minority oversampling technique and AdaboostM1 were used to correct for the skewed distribution. Classifiers were trained using five different pattern recognition algorithms. RESULTS: Use of imbalanced learning techniques improved the balanced accuracy rate (BAR) of all classification methods (average BAR over all classification methods for spectra: oversampled data = 0.81, original = 0.63, P < 0.001; metabolite concentration: oversampled-data = 0.91, original = 0.75, P < 0.0001). Performance of all classifiers in discriminating ependymomas increased when oversampled data were used compared with original data for both complete spectra (F-measure P < 0.01) and metabolite profile (F-measure P < 0.001). CONCLUSION: Imbalanced learning techniques improve the classification accuracy of childhood brain tumors from MRS where group sizes differ and facilitate the inclusion of rarer tumor types into clinical decision support systems. Magn Reson Med 77:2114-2124, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID- 27404901 TI - Smart management of sample dilution using an artificial neural network to achieve streamlined processes and saving resources: the automated nephelometric testing of serum free light chain as case study. AB - BACKGROUND: Saving resources is a paramount issue for the modern laboratory, and new trainable as well as smart technologies can be used to allow the automated instrumentation to manage samples more efficiently in order to achieve streamlined processes. In this regard the serum free light chain (sFLC) testing represents an interesting challenge, as it usually causes using a number of assays before achieving an acceptable result within the analytical range. METHODS: An artificial neural network based on the multi-layer perceptron (MLP ANN) was used to infer the starting dilution status of sFLC samples based on the information available through the laboratory information system (LIS). After the learning phase, the MLP-ANN simulation was applied to the nephelometric testing routinely performed in our laboratory on a BN ProSpec(r) System analyzer (Siemens Helathcare) using the N Latex FLC kit. RESULTS: The MLP-ANN reduced the serum kappa free light chain (kappa-FLC) and serum lambda free light chain (lambda-FLC) wasted tests by 69.4% and 70.8% with respect to the naive stepwise dilution scheme used by the automated analyzer, and by 64.9% and 66.9% compared to a "rational" dilution scheme based on a 4-step dilution. CONCLUSIONS: Although it was restricted to follow-up samples, the MLP-ANN showed good predictive performance, which alongside the possibility to implement it in any automated system, made it a suitable solution for achieving streamlined laboratory processes and saving resources. PMID- 27404902 TI - The effects of the Bali Yoga Program (BYP-BC) on reducing psychological symptoms in breast cancer patients receiving chemotherapy: results of a randomized, partially blinded, controlled trial. AB - Background Several cognitive behavioral interventions have been reported to reduce psychological symptoms in breast cancer (BC) patients. The goal of this study was to evaluate the effects of a yoga intervention in reducing depression and anxiety symptoms in BC patients. Methods This study was a randomized, partially blinded, controlled trial comparing a standardized yoga intervention to standard care. It was conducted at three medical centers in Montreal, Canada. Eligible patients were women diagnosed with stage I-III BC receiving chemotherapy. Participants were randomly assigned to receive yoga intervention immediately (experimental group, n=58) or after a waiting period (n=43 control group). The Bali Yoga Program for Breast Cancer Patients (BYP-BC) consisted of 23 gentle Hatha asanas (poses), 2 prayanamas (breathing techniques), shavasanas (relaxation corpse poses) and psychoeducational themes. Participants attended eight weekly sessions lasting 90 min each and received a DVD for home practice with 20- and 40-min sessions. Participants in the wait list control group received standard care during the 8-week waiting period. Results A total of 101 participants took part in the final intention-to-treat analyses. The repeated measures analyses demonstrated that depression symptoms increased in the control group (p=0.007), while no change was reported in the BYP-BC group (p=0.29). Also, depression symptoms decreased in the WL control group after receiving the BYP-BC intervention (p=0.03). Finally, there was no statistical significance in terms of anxiety symptoms (p=0.10). Conclusions Results support the BYP-BC intervention as a beneficial means of reducing and preventing the worsening of depression symptoms during chemotherapy treatment. PMID- 27404903 TI - Advancing medical education: connecting interprofessional collaboration and education opportunities with integrative medicine initiatives to build shared learning. AB - BackgroundImproved teamwork between conventional and complementary medicine (CM) practitioners is indicated to achieve effective healthcare. However, little is known about interprofessional collaboration and education in the context of integrative medicine (IM). MethodsThis paper reports the findings from a constructivist-grounded theory method study that explored and highlighted Australian medical students' experiences and opportunities for linking interprofessional collaboration and learning in the context of IM. Following ethical approval, in-depth semi-structured interviews were conducted with 30 medical students from 10 medical education faculties across Australian universities. Results Medical students recognised the importance of interprofessional teamwork between general medical practitioners and CM professionals in patient care and described perspectives of shared responsibilities, profession-specific responsibilities, and collaborative approaches within IM. While students identified that limited interprofessional collaboration currently occurred in the medical curriculum, interprofessional education was considered a means of increasing communication and collaboration between healthcare professionals, helping coordinate effective patient care, and understanding each healthcare team members' professional role and value. Conclusions The findings suggest that medical curricula should include opportunities for medical students to develop required skills, behaviours, and attitudes for interprofessional collaboration and interprofessional education within the context of IM. While this is a qualitative study that reflects theoretical saturation from a selected cohort of medical students, the results also point to the importance of including CM professionals within interprofessional collaboration, thus contributing to more person-centred care. PMID- 27404904 TI - A comparative study of the antacid effect of raw spinach juice and spinach extract in an artificial stomach model. AB - BackgroundSpinacia oleracea known as spinach is a green-leafy vegetable consumed by people across the globe. It is reported to possess potent medicinal properties by virtue of its numerous antioxidant phytoconstituents, together termed as the natural antioxidant mixture (NAO). The present study compares the antacid effect of raw spinach juice with an antioxidant-rich methanolic extract of spinach (NAOE) in an artificial stomach model. MethodsThe pH of NAOE at various concentrations (50, 100 and 200 mg/mL) and its neutralizing effect on artificial gastric acid was determined and compared with that of raw spinach juice, water, the active control sodium bicarbonate (SB) and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid for the test compounds. The neutralizing capacity of test compounds was determined in vitro using the classical titration method of Fordtran. Results NAOE (50, 100 and 200 mg/mL), spinach juice, SB and ENO showed significantly better acid-neutralizing effect, consistent duration of neutralization and higher antacid capacity when compared with water. Highest antacid activity was demonstrated by ENO and SB followed by spinach juice and NAOE200. Spinach juice exhibited an effect comparable to NAOE (200 mg/mL). ConclusionsThus, it may be concluded that spinach displays significant antacid activity be it in the raw juice form or as an extract in methanol. PMID- 27404905 TI - Medication therapy management (MTM): an innovative approach to improve medication adherence in diabetics. AB - BACKGROUND: Medication therapy management (MTM) is a pharmacist-led professional service, one of the main aims of which is to improve patient medication adherence. Ensuring adequate adherence to the prescribed therapeutic regimen is one of the major challenges in attaining the desired therapeutic goals in diabetics. The objective of this study was to implement MTM in diabetic patients and to identify its effectiveness in improving patient medication adherence. METHODS: A prospective interventional study was carried out within a 1-year period in KIMS-Al-Shifa Hospital, which is a tertiary care referral hospital in Malabar region of Kerala, including inpatients with type 2 diabetes mellitus in the general medicine department of the hospital. The MTM programme was applied in selected patients, including personal medication record, medication-related action plan and detailed counselling. Adherence was measured using the Modified Morisky Medication Adherence Scale-4 both before and after the programme. RESULTS: A total of 104 patients were included in the study. The adherence of patients to anti-diabetic therapy was very low, which showed significant improvement after applying intervention (p-value<0.05 in a paired t-test). Initially, only 37.5% had high adherence which was increased to 59.5% after intervention. Age and educational status were identified to have a significant impact on patient medication adherence (p-value<0.05 in a chi2-test). CONCLUSIONS: Medication adherence is a key component of self-management for patients with diabetes. A pharmacist-led MTM programme if appropriately designed and implemented will have a potential positive impact on medication adherence in diabetic patients. PMID- 27404906 TI - Carbon-Encapsulated Hollow Porous Vanadium-Oxide Nanofibers for Improved Lithium Storage Properties. AB - Carbon-encapsulated hollow porous vanadium-oxide (C/HPV2O5) nanofibers have been fabricated using electrospinning and postcalcination. By optimized postcalcination of vanadium-nitride and carbon-nanofiber composites at 400 degrees C for 30 min, we synthesized a unique architecture electrode with interior void spaces and well-defined pores as well as a uniform carbon layer on the V2O5 nanofiber surface. The optimized C/HPV2O5 electrode postcalcined at 400 degrees C for 30 min showed improved lithium storage properties with high specific discharge capacities, excellent cycling durability (241 mA h g(-1) at 100 cycles), and improved high-rate performance (155 mA h g(-1) at 1000 mA g( 1)), which is the highest performance in comparison with previously reported V2O5 based cathode materials. The improved electrochemical feature is due to the attractive properties of the carbon-encapsulated hollow porous structure: (I) excellent cycling durability with high specific capacity relative to the adoption of carbon encapsulation as a physical buffer layer and the effective accommodation of volume changes due to the hollow porous structure, (II) improved high-rate performance because of a shorter Li-ion diffusion pathway resulting from interior void spaces and well-defined pores at the surface. This unique electrode structure can potentially provide new cathode materials for high performance lithium-ion batteries. PMID- 27404907 TI - A three-dimensional metal grid mesh as a practical alternative to ITO. AB - The development of a practical alternative to indium tin oxide (ITO) is one of the most important issues in flexible optoelectronics. In spite of recent progress in this field, existing approaches to prepare transparent electrodes do not satisfy all of their essential requirements. Here, we present a new substrate embedded tall (~350 nm) and thin (~30 nm) three-dimensional (3D) metal grid mesh structure with a large area, which is prepared via secondary sputtering. This structure satisfies most of the essential requirements of transparent electrodes for practical applications in future opto-electronics: excellent optoelectronic performance (a sheet resistance of 9.8 Omega?(-1) with a transmittance of 85.2%), high stretchability (no significant change in resistance for applied strains <15%), a sub-micrometer mesh period, a flat surface (a root mean square roughness of approximately 5 nm), no haze (approximately 0.5%), and strong adhesion to polymer substrates (it survives attempted detachment with 3M Scotch tape). Such outstanding properties are attributed to the unique substrate-embedded 3D structure of the electrode, which can be obtained with a high aspect ratio and in high resolution over large areas with a simple process. As a demonstration of its suitability for practical applications, our transparent electrode was successfully tested in a flexible touch screen panel. We believe that our approach opens up new practical applications in wearable electronics. PMID- 27404908 TI - Characterizing Oxygen Local Environments in Paramagnetic Battery Materials via (17)O NMR and DFT Calculations. AB - Experimental techniques that probe the local environment around O in paramagnetic Li-ion cathode materials are essential in order to understand the complex phase transformations and O redox processes that can occur during electrochemical delithiation. While Li NMR is a well-established technique for studying the local environment of Li ions in paramagnetic battery materials, the use of (17)O NMR in the same materials has not yet been reported. In this work, we present a combined (17)O NMR and hybrid density functional theory study of the local O environments in Li2MnO3, a model compound for layered Li-ion batteries. After a simple (17)O enrichment procedure, we observed five resonances with large (17)O shifts ascribed to the Fermi contact interaction with directly bonded Mn(4+) ions. The five peaks were separated into two groups with shifts at 1600 to 1950 ppm and 2100 to 2450 ppm, which, with the aid of first-principles calculations, were assigned to the (17)O shifts of environments similar to the 4i and 8j sites in pristine Li2MnO3, respectively. The multiple O environments in each region were ascribed to the presence of stacking faults within the Li2MnO3 structure. From the ratio of the intensities of the different (17)O environments, the percentage of stacking faults was found to be ca. 10%. The methodology for studying (17)O shifts in paramagnetic solids described in this work will be useful for studying the local environments of O in a range of technologically interesting transition metal oxides. PMID- 27404909 TI - Political strategies in difficult times - The "backstage" experience of Swedish politicians on formal priority setting in healthcare. AB - This paper contributes to the knowledge on the governing of healthcare in a democratic context in times of austerity. Resource allocation in healthcare is a highly political issue but the political nature of healthcare is not always made clear and the role of politicians is often obscure. The absence of politicians in rationing/disinvestment arrangements is usually explained with blame-shifting arguments; they prefer to delegate "the burden of responsibility" to administrative agencies or professionals. Drawing on a case where Swedish regional politicians involved themselves in setting priorities at a more detailed level than previously, the findings suggest that the subject of "blame avoidance" is more complicated than usually assumed. A qualitative case study was designed, involving semi-structured interviews with 14 regionally elected politicians in one Swedish health authority, conducted in June 2011. The interviews were analysed through a thematic analysis in accordance with the "framework approach" by Ritchie and Lewis. Findings show that an overarching strategy among the politicians was to appear united and to suppress conflict, which served to underpin the vital strategy of bringing the medical profession into the process. A key finding is the importance that politicians, when appearing "backstage", attach to the prevention of blame from the medical profession. This case illustrates that one has to take into account that priority settings requires various types of skills and knowledges - not only technical but also political and social. Another important lesson points toward the need to broaden the political leadership repertoire, as leadership in the case of priority setting is not about politicians being all in or all out. The results suggest that in a priority-setting process it is of importance to have politics on-board at an early stage to secure loyalty to the process, although not necessarily being involved in all details. PMID- 27404910 TI - Alcohol abstention in early adulthood and premature mortality: Do early life factors, social support, and health explain this association? AB - OBJECTIVE: Adult alcohol abstainers have a heightened risk of premature mortality compared to light-to-moderate drinkers. We examine three plausible explanations, other than lack of alcohol, for this observed difference: Abstainers 1) have early life disadvantages that undermine long-term health; 2) lack social support; 3) are less healthy. METHOD: In the National Child Development Study, an ongoing national British cohort study of individuals born in 1958, we investigated whether early life disadvantages, lack of social support, and poor physical health reduce or eliminate the elevated risk of mortality through age 51 among those abstaining from alcohol at age 33. Using Cox proportional hazard models in a stepwise approach we examined whether the alcohol-mortality relationship changed when potential confounders were included. RESULTS: The risk of mortality by age 51 was greater among age-33 abstainers compared to light drinkers (Hazard Ratio [HR] = 2.18; 95% CI = 1.40, 3.40). Including early life disadvantages and social support in the hazard models did not alter these associations (HR = 2.12; 95% CI = 1.27, 3.54). Including physical health in the model resulted in a 25% reduction in risk of death among abstainers, though the difference in risk remained statistically significant (HR = 1.75; 95% CI = 1.04, 2.94). CONCLUSIONS: Abstaining from alcohol in early adulthood, in comparison to light drinking, predicts increased risk for premature mortality, even after accounting for numerous early and young adult confounders. Future research should examine potential moderators of this association. PMID- 27404911 TI - Controlling Gel Structure to Modulate Cell Adhesion and Spreading on the Surface of Microcapsules. AB - The surface properties of implanted materials or devices play critical roles in modulating cell behavior. However, the surface properties usually affect cell behaviors synergetically so that it is still difficult to separately investigate the influence of a single property on cell behavior in practical applications. In this study, alginate-chitosan (AC) microcapsules with a dense or loose gel structure were fabricated to understand the effect of gel structure on cell behavior. Cells preferentially adhered and spread on the loose gel structure microcapsules rather than on the dense ones. The two types of microcapsules exhibited nearly identical surface positive charges, roughness, stiffness, and hydrophilicity; thus, the result suggested that the gel structure was the principal factor affecting cell behavior. X-ray photoelectron spectroscopy analyses demonstrated that the overall percentage of positively charged amino groups was similar on both microcapsules. The different gel structures led to different states and distributions of the positively charged amino groups of chitosan, so we conclude that the loose gel structure facilitated greater cell adhesion and spreading mainly because more protonated amino groups remained unbound and exposed on the surface of these microcapsules. PMID- 27404912 TI - Enhanced Conversion Efficiencies in Dye-Sensitized Solar Cells Achieved through Self-Assembled Platinum(II) Metallacages. AB - Two-component self-assembly supramolecular coordination complexes with particular photo-physical property, wherein unique donors are combined with a single metal acceptor, can be utilized for many applications including in photo-devices. In this communication, we described the synthesis and characterization of two component self-assembly supramolecular coordination complexes (SCCs) bearing triazine and porphyrin faces with promising light-harvesting properties. These complexes were obtained from the self-assembly of a 90 degrees Pt(II) acceptor with 2,4,6-tris(4-pyridyl)-1,3,5-triazine (TPyT) or 5,10,15,20-Tetra(4-pyridyl) 21H,23H-porphine (TPyP). The greatly improved conversion efficiencies of the dye sensitized TiO2 solar cells were 6.79 and 6.08 respectively, while these SCCs were introduced into the TiO2 nanoparticle film photoanodes. In addition, the open circuit voltage (Voc) of dye-sensitized solar cells was also increased to 0.769 and 0.768 V, which could be ascribed to the inhibited interfacial charge recombination due to the addition of SCCs. PMID- 27404913 TI - The psychiatric treatment of 'behavioural problems' in adolescence: Between coercion and socialisation. AB - A 2005 report from the French Institute for Medical Research highlighted factors likely to prompt 'behavioural problems' in children and adolescents, and recommended early identification of at-risk families. A number of mental health professionals rose up against such medicalisation of social issues. This ethnographic study was conducted in this climate, in a psychiatric unit, located in a disadvantaged area in the outskirts of Paris, that specialises in adolescents with such problems. The research emphasised how professionals resist being instrumentalised by juvenile counselling services and the justice system, the observed practices bearing traces of critiques of psychiatric institutions since the 1960s. Psychiatrists thus try to justify and legitimate their interventions, which are co-constructed by relevant counselling and mental health professionals and, as much as possible, adolescents and their parents. Consequently, full understanding of institutionalisation, beyond its aspects of constraint and subjection, also requires consideration of its potential as a step in the socialisation process, especially for adolescents from working class backgrounds bereft of social and cultural capital. Contact with professionals may confer a kind of power, 'the power to speak'. At least, that is what the professionals try to give them using the 'pedagogy of reflexivity'. PMID- 27404915 TI - Key role in ecosystem functioning of scavengers reliant on a single common species. AB - The importance of species richness in maintaining ecosystem function in the field remains unclear. Recent studies however have suggested that in some systems functionality is maintained by a few abundant species. Here we determine this relationship by quantifying the species responsible for a key ecosystem role, carcass removal by scavengers. We find that, unlike those within largely unaltered environments, the scavenger community within our highly altered system is dominated by a single species, the Carrion crow, despite the presence of a number of other scavenging species. Furthermore, we find no relationship between abundance of crows and carcass removal. However, the overall activity of crows predicts carcass biomass removal rate in an asymptotic manner, suggesting that a relatively low level of abundance and scavenging activity is required to maintain this component of ecosystem function. PMID- 27404914 TI - Attitudes toward medication-assisted treatment among fishermen in Kuantan, Malaysia, who inject drugs. AB - Fishermen who inject drugs represent an understudied group at high risk for HIV in Malaysia. This study describes fishing, drug use, and attitudes toward medication-assisted treatment (MAT) for opioid use disorders. Thirty-four male ethnic Malay fishermen completed semistructured interviews analyzed by content analysis. Analysis revealed four themes surrounding opioids, which they called ubat ("medicine"): (a) the fishing lifestyle facilitating substance use, (b) previous unsuccessful attempts to quit, (c) categorizing substances as haram or halal, and (d) attitudes toward MAT. Fishermen's environment permits substance use, including injecting drugs on boats. Fishermen expressed more positive attitudes toward methadone and negative attitudes toward buprenorphine. PMID- 27404916 TI - Isolation and Cellular Phenotyping of Mesenchymal Stem Cells Derived from Synovial Fluid and Bone Marrow of Minipigs. AB - Mesenchymal stem cells (MSCs) have been established after isolation from various tissue sources, including bone marrow and synovial fluid. Recently, synovial fluid-derived MSCs were reported to have multi-lineage differentiation potential and immunomodulatory features, which indicates that these cells can be used for tissue engineering and systemic treatments. This study presents a protocol for simple and non-invasive isolation of MSCs derived from the bone marrow and synovial fluid of minipigs to analyze cell surface markers for cell phenotyping and in vitro culturing. Using sexually mature six-month-old minipigs, bone marrow was extracted from the iliac crest bone using a bone marrow extractor, and the synovial fluid was aspirated from the femorotibial joint. Procedures for the collection of samples from both sources were non-invasive. The protocols for effective isolation of MSCs from harvested cell sources and for creating in vitro culture conditions to expand stable MSCs from minipigs and the application of systemic autologous treatments are provided. For cell phenotyping, the cell surface markers of both cells were analyzed using flow cytometry. In the results, the MSCs were isolated from the synovial fluid of the minipigs and showed that synovial-fluid-derived MSCs have a similar morphology and cell phenotype to bone marrow-derived MSCs. Therefore, non-invasively obtained synovial fluid is a valuable source of MSCs. PMID- 27404918 TI - Audrey Naylor, MD, DrPH (1931-2016). PMID- 27404917 TI - Impact of Ions on Individual Water Entropy. AB - Solutes determine the properties of a solution. In this study, we probe ionic solutions through the entropy of individual water molecules in the solvation shells around different cations and anions. Using a method recently developed by our group, we show the solvation shell entropy stemming from the individual contributions correlates extremely well with experimental values for both polarizable and nonpolarizable force fields. The behavior of water entropy as a function of distance reveals significant (~20%) contributions from the second solvation shell even for the low concentration considered here. While for the cations, contributions from both translational and rotational entropy loss are similar in different solvation shells, water around anions loses much more rotational entropy due to their ability to accept hydrogen bonds. Most importantly, while charge density of cations or anions correlates with the translational entropy loss, anions with similar charge density as that of cations has a much stronger and long-range effect on water. We also show how the modulation of water entropy by ions is correlated to the structural modifications of hydration shell. This study thus provides a step toward understanding the entropic behavior of water in molecular recognition processes between proteins and drug molecules. PMID- 27404919 TI - Emergence of superconductivity in (NH3)yMxMoSe2 (M: Li, Na and K). AB - We report syntheses of new superconducting metal-doped MoSe2 materials (MxMoSe2). The superconducting MxMoSe2 samples were prepared using a liquid NH3 technique, and can be represented as '(NH3)yMxMoSe2'. The Tcs of these materials were approximately 5.0 K, independent of x and the specific metal atom. X-ray diffraction patterns of (NH3)yNaxMoSe2 were recorded using polycrystalline powders. An increase in lattice constant c showed that the Na atom was intercalated between MoSe2 layers. The x-independence of c was observed in (NH3)yNaxMoSe2, indicating the formation of a stoichiometric compound in the entire x range, which is consistent with the x-independence of Tc. A metallic edge of the Fermi level was observed in the photoemission spectrum at 30 K, demonstrating its metallic character in the normal state. Doping of MoSe2 with Li and K also yielded superconductivity. Thus, MoSe2 is a promising material for designing new superconductors, as are other transition metal dichalcogenides. PMID- 27404921 TI - [Treatment of osteoporosis - influence on fractures and mortality]. PMID- 27404920 TI - Structural Characterization of H1N1 Nucleoprotein-Nucleozin Binding Sites. AB - Influenza viruses are among the most common pathogens that threaten the health of humans and animals worldwide. Various anti-viral therapeutic agents are currently used for treatment and prophylaxis of influenza virus, but the targets of these drugs are easily mutated and result in resistance. Therefore, medications that have broad spectrum coverage are urgently needed to combat with the disease. Since nucleoprotein is regarded as a druggable target due to its conserved sequence and important functions during influenza virus life cycle, numerous studies are focused on this protein in attempts to develop broad-spectrum anti influenza therapeutics. Recently, a novel small molecule compound, nucleozin, was found to induce large aggregates of nucleoprotein, which in turn caused cessation of virus replication. However, the aggregation-inducing mechanism of nucleozin has not been unveiled. Here we report the crystal structure of nucleoprotein nucleozin complex at 3 A resolution, which shows the binding sites of nucleozin at nucleoprotein for the first time. The complex structure reveals how nucleoprotein and nucleozin interact with each other and hence result in nucleoprotein aggregates. The structural information is envisaged to help accelerate the development of anti-influenza therapeutic agents. PMID- 27404922 TI - [What is the maximal dosage of biotin?]. PMID- 27404923 TI - [Statins reduce cardiovascular risk in patients with type 1 diabetes]. PMID- 27404924 TI - [Treatment of metastatic malignant melanoma]. PMID- 27404925 TI - [Coronary heart dieseas: Unsaturated fatty acids aren't a panacea]. PMID- 27404926 TI - [Every second smoker shows symptoms despite good pulmonary function]. PMID- 27404927 TI - [Not Available]. PMID- 27404928 TI - [63-year old man with dyspnea and right heart failure]. PMID- 27404929 TI - [Not Available]. PMID- 27404930 TI - [Relapsing fever: an almost forgotten disease in focus again]. AB - Introduction | Relapsing fevers, transmitted by arthropods, are rarely encountered in Germany, thus they are often not considered as differential diagnosis in febrile patients. In the last months, more than fourty cases of louse-borne relapsing fever were diagnosed in asylum seekers in Germany. Some of the patients had to be admitted to intensive care units, one patient died despite therapy. Pathogen, disease and diagnosis | The causative agents are spirochetes of the genus borrelia, which can reach high densities in patient blood. Depending on the vector and the region, different species are prevalent worldwide. For diagnosis, appropriate techniques include direct detection by microscopy or PCR from EDTA-blood. Ordering such tests should not be delayed when there is suspicion for relapsing fever. Besides, malaria can also be excluded with microscopy of blood smears. Therapy | First-line antibiotics include tetracyclines and penicillin, acquired resistance has not yet been observed. Frequently patients develop a Jarisch-Herxheimer reaction shortly after initiation of therapy, requiring hospitalization or intensive care treatment. Managing the treatment exclusively in an outpatient setting is not recommended. Especially in migrants with febrile illness, relapsing fever is an important differential diagnosis. PMID- 27404931 TI - [Brucellosis, an overview and current aspects]. AB - Although brucellosis, a zoonosis mostly associated with sheep, goats and cattle, is not endemic in Germany, it is a relevant imported infectious disease. If patients suffer from fever of unknown origin after a stay in highly endemic countries like the Mediterranean area or the Arab world, it is mandatory to formally exclude brucellosis. Cultural methods are the diagnostic gold standard, but due to special methodical and infrastructural requirements it is essential to inform the laboratory at suspicion of infection. The treatment of brucellosis is challenging and usually based on a long-term combination regime using doxycycline and rifampin for at least 6 weeks. PMID- 27404932 TI - [How to perform contrast enhanced ultrasound]. AB - This review article reports on practical and clinical aspects of contrast enhanced ultrasound (CEUS). We discuss practical recommendations and advice on the use of CEUS. PMID- 27404933 TI - [A rare cause of diabetes mellitus]. AB - Medical history and clinical examination: We report on a 52-year-old lean female patient with diabetes mellitus, treated with various glucose-lowering medications including insulin for 6 years. Both her mother and great-grandmother were also diagnosed with diabetes. At admission, she presents with good glycemic control and no signs of diabetes-related comorbidities. LABORATORY TESTS: HbA1c is 6 %. On the basis of positive family history for diabetes, normal body weight and negative antibodies against islet-cell antigens, we perform blood molecular genetic analyses with the suspicion of a genetic form of diabetes. Genetic tests reveal a monogenic form of diabetes (MODY, Maturity Onset Diabetes of the Young) due to an heterozygous mutation in exon 6 of the glucokinase (GCK) gene. The same mutation is subsequently detected in the patient's mother. DIAGNOSIS, TREATMENT AND COURSE: We diagnose MODY2 diabetes due to a glucokinase gene mutation. Repaglinide therapy is withdrawn due to lack of solid literature data showing beneficial cardiometabolic outcomes in patients with diabetes. Based on the MODY diagnosis, we recommend sulfonylurea treatment, which is however rejected by the patient due to a history of hypoglycemic episodes under the lowest dose. Thus, sitagliptin-treatment is continued under regular visits in our outpatient clinic. CONCLUSIONS: The joint presence of a positive family history, age under 25 years at diagnosis of diabetes, normal bodyweight, negative diabetes-specific autoantibodies and mild hyperglycaemia should raise the suspicion of a monogenic form of diabetes such as MODY and result in molecular-genetic testing. PMID- 27404934 TI - [Lymphoepithelial sialadenitis (LESA)-like Thymic hyperplasia: A case report]. AB - A 43-year-old man was admitted to this hospital because of shortness of breath and chest pain. The patient had a history of cardiac surgery at the age of seven (due to a congenital heart defect), and of intracerebral bleeding which had occurred at the age of 23. There was no history of autoimmune disorders. Computed tomography revealed a well-circumscribed anterior mediastinal mass, measuring 4 * 3 * 3 cm with calcification and cystic components. Therefore a malignant tumor was suspected for which a thymectomy was performed. Histopathological evaluation revealed an unusual type of thymic hyperplasia strongly resembling lymphoepithelial sialadenitis (LESA) of the salivary glands. A CT scan of the neck, thorax and abdomen for staging did not display lymphadenopathy or splenomegaly. The laboratory tests revealed no abnormality. Clinical, there were no signs of lymphoma. Actually, the patient is in our aftercare. Taken together, lymphoepithelial sialadentis of the thymus is a very rare disorder and was first described in 2012. This disorder seems to be benigne and no other treatment is needed after thymectomy. PMID- 27404935 TI - [Ultrasound screening for abdominal aortic aneurysms - a rational measure to prevent sudden rupture]. AB - The ruptured abdominal aortic aneurysm (AAA) has still a high hospital mortality rate of about 50 % (intervention and non-corrective treatment combined). With an easy non-invasive and inexpensive measure such as the ultrasound screening rupture threatened aneurysms can be recognized in time and then treated prophylactically, hemorrhagic shock can be avoided. Screening programs in England and Sweden currently describe an AAA prevalence of 1.5 % among screened 65-year old males. With an absolute risk reduction for aneurysm-related death of 15.1 per 10,000 men invited for screening and a cost of L 7,370 per quality-adjusted life year (QALY), screening for this target group is highly cost-effective. Comprehensive AAA screening requires defined criteria for the quality of the aortic ultrasound examination and for the surgical treatment of detected large AAA. These interventions should be concentrated in centers obligated to quality registry documentation. Patients with smaller AAA, requiring no repair, should be included in a surveillance program, also with registry of their long-term data. PMID- 27404936 TI - [Assessment of risk of sudden cardiac death in patients with hypertrophic cardiomyopathy]. AB - Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterized by left ventricular hypertrophy with or without concomitant outflow tract obstruction. Identification of patients with HCM who are at high risk of sudden cardiac death (SCD) is crucial as those patients are likely to benefit from an implantable cardioverter defibrillator (ICD). Based on the HCM Risk-SCD study published in 2013, that included 3675 HCM patients with 24 313 years of follow up, a new clinical risk prediction model for sudden cardiac death was developed. This model was included in the recently released 2014 ESC guidelines. This review summarizes the changes in the prediction model and the resulting recommendations and discusses potential risks and limitations of the new score. PMID- 27404937 TI - [Body Mass Index makes headlines - When is mortality rate lowest?]. AB - "People with obesity live longer" - headlines like these are common. Recently published epidemiological studies however provide new food for thought: how is a body mass index (BMI) in the overweight range associated with total mortality? There are many studies showing that a BMI outside the normal range is associated with a higher total mortality. In contrast, there are indications that a BMI in the overweight range is associated with a lower mortality rate. These observations should be interpreted with caution, because of the limitations of the BMI as a measure of overweight and obesity and because the results are based on cohort data. There is currently no reason to deviate from the recommendations regarding the indications for weight loss of the German Obesity Association. PMID- 27404938 TI - [Low seroprevalence of syphilis and HIV in refugees and asylum seekers in Germany in 2015]. AB - Background | Currently only estimates exist of seroprevalence of syphilis and human immunodeficiency virus (HIV) in refugees arriving in Germany during the current refugee crisis. Objectives | To assess the prevalence of syphilis and human immunodeficiency virus (HIV) in refugees arriving in northern Germany in 2015. Materials and methods | In a cross-sectional study in 790 patients from all age groups tests for serological markers of treponema pallidum and in 789 patients for human immunodeficiency virus (HIV) were performed in August 2015 in reception centers in northern Germany. Results | The overall prevalence of treponema pallidum antibodies was 0.13 % (1/790; [95 % CI: 0 - 0.4]). HIV antibodies were positive in two refugees from sub-Saharan Africa (2/789; 0.25 %, [95 % CI: 0 - 0.6]). Conclusions | This study showed a low prevalence of treponema pallidum antibodies and human immunodeficiency virus infection (HIV) in a German refugee cohort, not significantly different from German controls. PMID- 27404939 TI - [Louse-borne-relapsing-fever in refugees from the Horn of Africa; a case series of 25 patients]. AB - Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum Munchen Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn't see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa. PMID- 27404941 TI - Application of a MABEL Approach for a T-Cell-Bispecific Monoclonal Antibody: CEA TCB. AB - CEA TCB is a novel T-cell-bispecific (TCB) antibody targeting the carcinoembryonic antigen (CEA) expressed on tumor cells and the CD3 epsilon chain (CD3e) present on T cells, which is currently in Phase 1 clinical trials (NCT02324257) for the treatment of CEA-positive solid tumors. Because the human CEA (hCEA) binder of CEA TCB does not cross-react with cynomolgus monkey and CEA is absent in rodents, alternative nonclinical safety evaluation approaches were considered. These included the development of a cynomolgus monkey cross-reactive homologous (surrogate) antibody (cyCEA TCB) for its evaluation in cynomolgus monkey and the development of double-transgenic mice, expressing hCEA and human CD3e (hCEA/hCD3e Tg), as a potential alternative species for nonclinical safety studies. However, a battery of nonclinical in vitro/ex vivo experiments demonstrated that neither of the previous approaches provided a suitable and pharmacologically relevant model to assess the safety of CEA TCB. Therefore, an alternative approach, a minimum anticipated biological effect level (MABEL), based on an in vitro tumor lysis assay was used to determine the starting dose for the first-in-human study. Using the most conservative approach to the MABEL assessment, a dose of 52 MUg was selected as a safe starting dose for clinical study. PMID- 27404942 TI - An Association Between Glatiramer Acetate and Malignant Melanoma. AB - A 43-year-old female receiving immunomodulatory therapy with glatiramer acetate (copaxone, GA) for relapsing, remitting multiple sclerosis was diagnosed with stage IIIB melanoma that recurred <7 months after resection and lymphadenectomy. In preparation for systemic therapy the patient discontinued GA, and shortly thereafter experienced spontaneous and complete clinical and radiographic resolution of her disease. The development and subsequent regression of melanoma in this patient may be due to the use and subsequent discontinuation of GA, and our discussion of the case includes the potential immunologic mechanisms that may provide an explanation for our findings. To the best of our knowledge, this case represents the first reported association between the immunomodulatory agent GA and malignant melanoma. PMID- 27404940 TI - In vivo imaging reveals impaired connectivity across cortical and subcortical networks in a mouse model of DYT1 dystonia. AB - Developing in vivo functional and structural neuroimaging assays in Dyt1 DeltaGAG heterozygous knock-in (Dyt1 KI) mice provide insight into the pathophysiology underlying DYT1 dystonia. In the current study, we examined in vivo functional connectivity of large-scale cortical and subcortical networks in Dyt1 KI mice and wild-type (WT) controls using resting-state functional magnetic resonance imaging (MRI) and an independent component analysis. In addition, using diffusion MRI we examined how structural integrity across the basal ganglia and cerebellum directly relates to impairments in functional connectivity. Compared to WT mice, Dyt1 KI mice revealed increased functional connectivity across the striatum, thalamus, and somatosensory cortex; and reduced functional connectivity in the motor and cerebellar cortices. Further, Dyt1 KI mice demonstrated elevated free water (FW) in the striatum and cerebellum compared to WT mice, and increased FW was correlated with impairments in functional connectivity across basal ganglia, cerebellum, and sensorimotor cortex. The current study provides the first in vivo MRI-based evidence in support of the hypothesis that the deletion of a 3-base pair (DeltaGAG) sequence in the Dyt1 gene encoding torsinA has network level effects on in vivo functional connectivity and microstructural integrity across the sensorimotor cortex, basal ganglia, and cerebellum. PMID- 27404943 TI - Improved Anti-Treg Vaccination Targeting Foxp3 Efficiently Decreases Regulatory T Cells in Mice. AB - INTRODUCTION: The critical role of regulatory T (Treg) cells in dampening immune responses against tumor cells is apparent. Therefore, several methods have been introduced for eliminating Treg. Among them, inducing immune responses against Treg cells expressing Foxp3 transcription factor is a hopeful approach to decrease the frequency of Tregs. In current study, we used the chimeric FoxP3 Fc(IgG) fusion construct/protein to effectively stimulate the immune responses against Treg cells. MATERIALS AND METHODS: Previously constructed FoxP3-Fc(IgG) DNA vaccine and its protein counterpart were injected into C57BL/6 mice in a prime/boost regimen. After 2 weeks, the mice were killed to measure the frequency of Tregs in their spleens, as well as analyze their specific cytokine production, T-cell proliferation, and CD8 T-cell cytotoxicity against FoxP3 protein. RESULTS: FACS analysis of FoxP3 CD4 cells in splenocytes revealed the efficiency of FoxP3 DNA-prime protein-boost strategy to decrease the Treg cells and further showed considerable superiority of Fc(IgG) fusion strategy. This significant reduction in Treg frequency was also concomitant with higher FoxP3-specific CTL and Th1 responses in FoxP3-Fc vaccinated animals. CONCLUSIONS: Prime/boost vaccination against FoxP3 in addition to enhanced antigen presentation by means of Fc fusion strategy could be successfully considered for Treg depletion studies. Validity of this approach should be experimentally tested in preclinical tumor models. PMID- 27404944 TI - Clinical Features and Complications of the HLA-B27-associated Acute Anterior Uveitis: A Metanalysis. AB - In this article, we report a literature-based metanalysis we have conducted to outline the clinical features of the HLA-B27 Acute Anterior Uveitis (AAU). The examined material was based on observational studies in which participants were affected by Acute Anterior Uveitis and divided into HLA B27+ and HLA B27-. We performed a search on articles with the words "HLA B27 uveitis" dated before May 2014. Among these, 29 articles were selected for a second review. After a further evaluation, 22 articles were analyzed. The clinical characteristics studied in the metanalysis were: (1) systemic disease; (2) sex distribution; (3) laterality; (4) visual acuity; (5) hypopion; (6) anterior chamber's fibrin; (7) elevated intraocular pressure (IOP) during inflammation; (8) glaucoma; (9) posterior synechiae; (10) cataract; (11) cystoid macular edema; (12) papillitis. We have calculated a relative risk (RR) for each outcome measured. The results obtained remark some of the peculiar features linked to the HLA B27 Acute Anterior Uveitis, such as strong association with ankylosing spondylitis (RR = 6.80) and systemic diseases (RR = 9.9), male prevalence (RR = 1.2), unilateral (RR = 1.1) or alternating bilateral (RR = 2.2) involvement, hypopion (RR = 5.5), fibrinous reaction and even papillitis (R = 7.7). Simultaneous bilateral (RR = 0.3) AAU is more frequent in HLA-B27 negative form. We report higher risk of elevated IOP and glaucoma (RR = 0.6) in B27- Acute Anterior Uveitis. No significant difference between HLA B 27 positive and negative AAU was observed according to final visual acuity and complications such as posterior synechiae, cataract, and maculare edema. We trust that this will inform on the clinical evaluation and therapeutic decision in addressing a still ill-defined ophthalmologic condition. PMID- 27404945 TI - Intramolecular backbone...backbone hydrogen bonds in polypeptide conformations. The other way around: E-turn. AB - In this study, we performed a detailed literature survey of the E-turn in peptides and proteins. This three-dimensional structural feature is characterized by an eleven-membered pseudo-cycle closed by an intramolecular backbone...backbone H-bond. Interestingly, in this motif the direction of the N H...O = C H-bond runs opposite to that of the much more popular and extensively investigated alpha-, beta-, and gamma-turns. We did not authenticate unequivocally the E-turn main-chain reversal topology in any linear short peptide. However, it is frequently observed in small cyclic peptides formed by four, five, and six amino acid residues with stringent geometric requirements. Rather surprisingly, E-turns do occur in proteins, although to a relatively moderate extent, as an isolated feature or in the turn segment of hairpin motifs based on two antiparallel, pleated beta-strands. Moreover, the E-turn may also host not only the seven-membered, intramolecularly H-bonded, pseudo-cycle termed gamma-turn, either of the classic or inverse type, but also one (or even two) cis peptide bond(s) or a beta-bulge conformation. Based on their phi, psi backbone torsion angles, we were able to classify the protein E-turns in six different families. Conformational energy computations using the DFT methodology were also performed on the E-turns adopted by the amino acid triplet -Gly-Gly-Gly- (Gly is the most commonly found residue at each of the three positions in our analysis of proteins). Again, in this computational study, six families of turns were identified, but only some of them resemble rather closely those extracted from our investigation on proteins. PMID- 27404947 TI - Sorption and desorption characteristics of methyl bromide during and after fumigation of pine (Pinus radiata D. Don) logs. AB - BACKGROUND: The sorption and desorption characteristics of methyl bromide (MB) were determined during and after fumigation of recently harvested pine (Pinus radiata D. Don) logs. The effects of dose (48 or 120 g m-3 ), degree of bark cover (0, 50 or 100%) and end-grain sealing (sealed or unsealed) on sorption and desorption were determined over time. RESULTS: Sorption of MB was proportional to the dose applied and dependent on the amount of end-grain sealed. After 16 h, an average of 70.7 +/- 2.5% of the initial concentration remained in the treated space when end-grains were sealed, whereas only 47.3 +/- 2.5% remained when unsealed. During aeration, MB was released from logs, initially ranging from 2.8 to 8.8 g . h m-3 , depending on the treatment. The rate of desorption quickly decreased during aeration. CONCLUSION: The surface area of a log is the most important factor influencing MB sorption and desorption rates, with greater surface area resulting in greater (de)sorption rates. Sorption data can now be combined with insect toxicity data to estimate a minimum effective dose of MB for further evaluation, while desorption data can be combined with fumigant plume modelling to assess worker safety. (c) 2016 Society of Chemical Industry. PMID- 27404946 TI - Simulations to Predict Clinical Trial Outcome of Bevacizumab Plus Chemotherapy vs. Chemotherapy Alone in Patients With First-Line Gastric Cancer and Elevated Plasma VEGF-A. AB - To simulate clinical trials to assess overall survival (OS) benefit of bevacizumab in combination with chemotherapy in selected patients with gastric cancer (GC), a modeling framework linking OS with tumor growth inhibition (TGI) metrics and baseline patient characteristics was developed. Various TGI metrics were estimated using TGI models and data from two phase III studies comparing bevacizumab plus chemotherapy vs. chemotherapy as first-line therapy in 976 GC patients. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, Eastern Cooperative Oncology Group (ECOG) score, albumin level, and Asian ethnicity were significant covariates in the final OS model. The model correctly predicted a decreased hazard ratio favorable to bevacizumab in patients with high baseline plasma VEGF-A above the median of 113.4 ng/L. Based on trial simulations, in trials enrolling patients with elevated baseline plasma VEGF-A (500 patients per arm), the expected hazard ratio was 0.82 (95% prediction interval: 0.70-0.95), independent of ethnicity. PMID- 27404948 TI - Roles of Energy/Charge Cascades and Intermixed Layers at Donor/Acceptor Interfaces in Organic Solar Cells. AB - The secret to the success of mixed bulk heterojunctions (BHJs) in yielding highly efficient organic solar cells (OSCs) could reside in the molecular structures at their donor/acceptor (D/A) interfaces. In this study, we aimed to determine the effects of energy and charge cascade structures at the interfaces by using well defined planar heterojunctions (PHJs) as a model system. The results showed that (1) the charge cascade structure enhanced VOC because it shuts down the recombination pathway through charge transfer (CT) state with a low energy, (2) the charge cascade layer having a wider energy gap than the bulk material decreased JSC because the diffusion of the excitons from the bulk to D/A interface was blocked; the energy of the cascade layers must be appropriately arranged for both the charges and the excitons, and (3) molecular intermixing in the cascade layer opened the recombination path through the low-energy CT state and decreased VOC. Based on these findings, we propose improved structures for D/A interfaces in BHJs. PMID- 27404949 TI - A rare case of biliary tract stenosis caused by intraductal varices diagnosed by single-operator per-oral cholangioscopy. PMID- 27404951 TI - The Scoop on Health: How Native American Newspapers Frame and Report Health News. AB - The health status of Native Americans is known to be lower than that of other Americans. One way to get relevant health information to this population is through Native-produced media. Tribal newspapers are the most popular form of Native media, consumed more often than their mainstream counterparts. As such, these community-based newspapers are meaningful tools for relevant health information gathering. This study content analyzes a census of health-related newspaper articles (N = 644) over a 1-year period from 20 Tribal newspapers across 10 regions designated by the U.S. Bureau of Indian Affairs. Findings profile the nature of health topics reported in Native news publications. Health news stories were shown to use episodic frames significantly more than thematic frames. Inclusion of supplementary information (e.g., causes/symptoms, treatment, and prevention) and inclusion of mobilizing information (i.e., provides readers resources for further action) were both shown to significantly differ by health topic. Results provide an important baseline understanding of how health news is reported in Native news publications. PMID- 27404950 TI - A Nanoarchitecture Based on Silver and Copper Oxide with an Exceptional Response in the Chlorine-Promoted Epoxidation of Ethylene. AB - The selective oxidation of ethylene to ethylene epoxide is highly challenging as a result of competing reaction pathways leading to the deep oxidation of both ethylene and ethylene oxide. Herein we present a novel catalyst based on silver and copper oxide with an excellent response in the selective oxidation pathway towards ethylene epoxide. The catalyst is composed of different silver nanostructures dispersed on a tubular copper oxide matrix. This type of hybrid nanoarchitecture seems to facilitate the accommodation of chlorine promoters, leading to high yields at low reaction temperatures. The stability after the addition of chlorine promoters implies a substantial improvement over the industrial practice: a single pretreatment step at ambient pressure suffices in contrast with the common practice of continuously feeding organochlorinated precursors during the reaction. PMID- 27404952 TI - Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte derived Macrophages. AB - A protocol is presented for cell culture of macrophage colony-stimulating factor (M-CSF) differentiated human monocyte-derived macrophages. For initiation of experiments, fresh or frozen monocytes are cultured in flasks for 1 week with M CSF to induce their differentiation into macrophages. Then, the macrophages can be harvested and seeded into culture wells at required cell densities for carrying out experiments. The use of defined numbers of macrophages rather than defined numbers of monocytes to initiate macrophage cultures for experiments yields macrophage cultures in which the desired cell density can be more consistently attained. Use of cryopreserved monocytes reduces dependency on donor availability and produces more homogeneous macrophage cultures. PMID- 27404955 TI - Synthesis and biological evaluation of novel propargylquinobenzothiazines and their derivatives as potential antiproliferative, anti-inflammatory, and anticancer agents. AB - Azaphenothiazines containing the quinoline ring, 8-10-substituted 6H quinobenzothiazines and 6H-diquinothiazine were transformed into new 6-propargyl and 6-dialkylaminobutynyl derivatives containing the triple bond. Most of them displayed strong antiproliferative actions against human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin A (PHA), strongly suppressed lipopolysaccharide (LPS)-induced TNF-alpha production by whole blood human cell cultures, and exhibited low cytotoxicity. Three propargylquinobenzothiazines with the bromine, trifluoromethyl, and methylthio groups at position 9 and propargyldiquinothiazine exhibited comparable actions to cisplatin against the L-1210 and SW-948 tumor lines. 6-Propargyl-9 trifluoromethylquinobenzothiazine was shown to block caspase 3 expression and inhibit expression of caspase 8 and 9 in Jurkat cells indicating its possible mechanism of action. These derivatives could be promising, potential therapeutics for treatment of neoplastic diseases and autoimmune disorders. PMID- 27404956 TI - Abstracts from the 31st Annual Meeting of the Academy of Surgical Research, Winston-Salem, North Carolina, October 8-10, 2015. PMID- 27404957 TI - Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1pdm infection in England. AB - Understanding how the geographic distribution of and movements within a population influence the spatial spread of infections is crucial for the design of interventions to curb transmission. Existing knowledge is typically based on results from simulation studies whereas analyses of real data remain sparse. The main difficulty in quantifying the spatial pattern of disease spread is the paucity of available data together with the challenge of incorporating optimally the limited information into models of disease transmission. To address this challenge the role of routine migration on the spatial pattern of infection during the epidemic of 2009 pandemic influenza in England is investigated here through two modelling approaches: parallel-region models, where epidemics in different regions are assumed to occur in isolation with shared characteristics; and meta-region models where inter-region transmission is expressed as a function of the commuter flux between regions. Results highlight that the significantly less computationally demanding parallel-region approach is sufficiently flexible to capture the underlying dynamics. This suggests that inter-region movement is either inaccurately characterized by the available commuting data or insignificant once its initial impact on transmission has subsided. PMID- 27404958 TI - LeftyA decreases Actin Polymerization and Stiffness in Human Endometrial Cancer Cells. AB - LeftyA, a cytokine regulating stemness and embryonic differentiation, down regulates cell proliferation and migration. Cell proliferation and motility require actin reorganization, which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). The present study explored whether LeftyA modifies actin cytoskeleton, shape and stiffness of Ishikawa cells, a well differentiated endometrial carcinoma cell line. The effect of LeftyA on globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry. Rac1 and PAK1 transcript levels were measured by qRT-PCR as well as active Rac1 and PAK1 by immunoblotting. Cell stiffness (quantified by the elastic modulus), cell surface area and cell volume were studied by atomic force microscopy (AFM). As a result, 2 hours treatment with LeftyA (25 ng/ml) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin, and decreased cell stiffness, surface area and volume. The effect of LeftyA on actin polymerization was mimicked by pharmacological inhibition of Rac1 and PAK1. In the presence of the Rac1 or PAK1 inhibitor LeftyA did not lead to significant further actin depolymerization. In conclusion, LeftyA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization, cell softening and cell shrinkage. PMID- 27404959 TI - The 2016 Academic Emergency Medicine Consensus Conference, "Shared Decision Making in the Emergency Department: Development of a Policy-relevant Patient centered Research Agenda" Diagnostic Testing Breakout Session Report. AB - Diagnostic testing is an integral component of patient evaluation in the emergency department (ED). Emergency clinicians frequently use diagnostic testing to more confidently exclude "worst-case" diagnoses rather than to determine the most likely etiology for a presenting complaint. Increased utilization of diagnostic testing has not been associated with reductions in disease-related mortality but has led to increased overall healthcare costs and other unintended consequences (e.g., incidental findings requiring further workup, unnecessary exposure to ionizing radiation or potentially nephrotoxic contrast). Shared decision making (SDM) presents an opportunity for clinicians to discuss the benefits and harms associated with diagnostic testing with patients to more closely tailor testing to patient risk. This article introduces the challenges and opportunities associated with incorporating SDM into emergency care by summarizing the conclusions of the diagnostic testing group at the 2016 Academic Emergency Medicine Consensus Conference on SDM. Three primary domains emerged: 1) characteristics of a condition or test appropriate for SDM, 2) critical elements of and potential barriers to SDM discussions on diagnostic testing, and 3) financial aspects of SDM applied to diagnostic testing. The most critical research questions to improve engagement of patients in their acute care diagnostic decisions were determined by consensus. PMID- 27404960 TI - Convergence of multimodal sensory pathways to the mushroom body calyx in Drosophila melanogaster. AB - Detailed structural analyses of the mushroom body which plays critical roles in olfactory learning and memory revealed that it is directly connected with multiple primary sensory centers in Drosophila. Connectivity patterns between the mushroom body and primary sensory centers suggest that each mushroom body lobe processes information on different combinations of multiple sensory modalities. This finding provides a novel focus of research by Drosophila genetics for perception of the external world by integrating multisensory signals. PMID- 27404961 TI - MACULAR MICROSTRUCTURAL FEATURES IN CHILDREN WITH TILTED DISK SYNDROME EVALUATED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY. AB - PURPOSE: To assess macular microstructure in eyes with tilted disk syndrome (TDS) and determine the relationship between TDS foveal morphology and visual function. METHODS: Twenty-six TDS eyes from 19 children (aged 5~15 years) with a spherical equivalent refraction (SER) of -3.1 +/- 1.3 diopter (D) and 28 control eyes from 14 children (aged 7~12 years) with a SER of -3.0 +/- 0.7 D were recruited. Horizontal and vertical optical coherence tomography scans through the fovea produced images that were segmented into eight intraretinal layers. Thicknesses of the total retina and each layer were measured at the foveal center and 12 other macular locations: 500 MUm, 1,000 MUm, and 1,500 MUm along the horizontal and vertical meridians. The relationships between TDS best correct visual acuity (BCVA) and the presence of photoreceptor inner/outer segment (IS/OS) junction line, IS/OS foveal bulge, and cone outer segment tip (COST) line were evaluated. RESULTS: The thickness of TDS central fovea, 218.94 +/- 22.20 MUm, was not significantly different from controls. The total retinal thickness in TDS eyes was thinner than controls at all peripheral locations (P < 0.05) except at 500 MUm and 1,000 MUm superiorly, and 1,500 MUm temporally. Tilted disk syndrome intraretinal layer thicknesses in the nasal and inferior regions varied significantly from controls (P < 0.05). Only 80.7% and 23.1% of TDS eyes had a normal foveal bulge and continuous COST line, respectively, compared with 100% and 96.4% of controls. The BCVA of TDS eyes was similar whether or not the foveal bulge or COST line was abnormal. CONCLUSION: Differences in intraretinal layer thickness may be correlated with defective vision. PMID- 27404962 TI - The pathogenesis of multifocal osteonecrosis. AB - Our objective was to study the incidence, etiology, and diagnosis of multifocal osteonecrosis (MFON) and its treatment options to facilitate an earlier diagnosis and to optimize treatment. A radiological investigation was performed in osteonecrosis patients with a high risk of MFON for a more accurate diagnosis between January 2010 and June 2015. For patients with osteonecrosis of both the hip and knee joints or for patients with a history of corticosteroid use or alcohol abuse who had osteonecrosis of one or more joints in the shoulder, ankle, wrist or elbow, magnetic resonance imaging (MRI) was also performed on other joints, regardless of whether these joints were symptomatic. Furthermore, we performed a radiological screening of 102 patients who had a negative diagnosis of MFON but were at a high risk; among them, another 31 MFON cases were successfully identified (30.4%). Thus, the incidence of MFON during the study period increased from 3.1% to 5.2%. Patients diagnosed with osteonecrosis and who are at a high risk of MFON should have their other joints radiologically examined when necessary. This will reduce missed diagnosis of MFON and facilitate an earlier diagnosis and treatment to achieve an optimal outcome. PMID- 27404963 TI - Dimensions of impulsivity in relation to eating disorder recovery. AB - OBJECTIVE: Impulsivity is associated with eating pathology, but different dimensions of impulsivity have not been extensively studied in the eating disorders. The current study examined the relationship between four facets of impulsivity and eating disorder recovery status. METHOD: Females formerly seen for an eating disorder were categorized as having an eating disorder (n = 53), partially recovered (n = 15), or fully recovered (n = 20) based on a diagnostic interview and physical, behavioral, and psychological indices. These groups and non-eating disorder controls were compared on impulsivity facets from the UPPS Impulsive Behavior Scale (UPPS): Urgency (negative urgency), Premeditation (lack of), Perseverance (lack of), and Sensation Seeking. RESULTS: Negative urgency (the tendency to engage in impulsive behavior to alleviate negative affect) was related to recovery. The fully recovered group and controls experienced significantly less negative urgency than those with a current eating disorder; the partially recovered group did not differ from the eating disorder group. DISCUSSION: Findings suggest that negative urgency may be a particularly important facet of impulsivity to target in therapeutic intervention for eating disorders, especially among those with a history of binge eating and/or purging. Future longitudinal work is needed to test a potential causal relationship between negative urgency and eating disorder recovery. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1027-1031). PMID- 27404964 TI - Variable Quality and Readability of Patient-oriented Websites on Colorectal Cancer Screening. AB - BACKGROUND & AIMS: The efficacy of colorectal cancer (CRC) screening is dependent on participation and subsequent adherence to surveillance. The internet increasingly is used for health information and is important to support decision making. We evaluated the accuracy, quality, and readability of online information on CRC screening and surveillance. METHODS: A Website Accuracy Score and Polyp Score were developed, which awarded points for various aspects of CRC screening and surveillance. Websites also were evaluated using validated internet quality instruments (Global Quality Score, LIDA, and DISCERN), and reading scores. Two raters independently assessed the top 30 websites appearing on Google.com. Portals, duplicates, and news articles were excluded. RESULTS: Twenty websites were included. The mean website accuracy score was 26 of 44 (range, 9-41). Websites with the highest scores were www.cancer.org, www.bowelcanceraustralia.org, and www.uptodate.com. The median polyp score was 3 of 10. The median global quality score was 3 of 5 (range, 2-5). The median overall LIDA score was 74% and the median DISCERN score was 45, both indicating moderate quality. The mean Flesch-Kincaid grade level was 11th grade, rating the websites as difficult to read, 30% had a reading level acceptable for the general public (Flesch Reading Ease > 60). There was no correlation between the Google rank and the website accuracy score (rs = -0.31; P = .18). CONCLUSIONS: There is marked variation in quality and readability of websites on CRC screening. Most websites do not address polyp surveillance. The poor correlation between quality and Google ranking suggests that screenees will miss out on high-quality websites using standard search strategies. PMID- 27404965 TI - Safety and Effectiveness of Direct-Acting Antiviral Agents for Treatment of Patients With Chronic Hepatitis C Virus Infection and Cirrhosis. AB - BACKGROUND & AIMS: Direct-acting antivirals (DAAs) have revolutionized treatment for patients with chronic hepatitis C virus (HCV) infection, leading to a high rates of sustained virologic response. This study assessed the real-world safety and effectiveness of DAA-based antiviral therapy for the treatment of cirrhotic patients with chronic HCV infection. METHODS: This international, multicenter cohort study included all consecutive patients with chronic HCV infection and cirrhosis who underwent antiviral therapy with second-generation DAAs. Data on all patients were analyzed to assess treatment response. Predictors of hepatic decompensation during antiviral therapy were assessed using Cox proportional hazards regression analyses. RESULTS: Until June 2015, 433 cirrhotic patients with chronic HCV infection started DAA-based treatment. Their mean age was 57.8 (+/-8.7) years, 277 (64.0%) patients were male, and 114 (26.3%) had a Child-Pugh (CP) score of B/C cirrhosis. The sustained virologic response rate at 12 weeks was similar among patients with a CP score of A (261 of 304 [85.9%]) and a CP score of B/C (83 of 101 [82.2%]; P = .37). A baseline albumin level less than 35 g/L (hazard ratio [HR], 3.11; 95% confidence interval [CI], 1.23-7.84; P = .005), baseline MELD score of 14 or higher (HR, 1.63; 95% CI, 1.03-2.61; P = .037), and HCV genotype 3 (HR, 2.05; 95% CI, 1.09-3.88; P = .033) were associated independently with hepatic decompensation during antiviral treatment among patients with a CP score of B/C. CONCLUSIONS: This large cohort study showed that therapy is safe and effective in patients with compensated (CP score of A) cirrhosis. For patients with decompensated (CP score of B/C) cirrhosis, albumin level less than 35 g/L, MELD score of 14 or greater, and HCV genotype 3 are important risk factors for hepatic decompensation during DAA-based treatment. Therefore, these patients require close monitoring during antiviral therapy or treatment should be deferred until after transplantation. PMID- 27404966 TI - Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines. AB - BACKGROUND & AIMS: Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown. METHODS: This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance. RESULTS: Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P = .54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P = .007) and past thiopurine failures (P = .007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22-1.00] and 0.32 [95% CI, 0.11 0.93], respectively). CONCLUSIONS: Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect. PMID- 27404967 TI - Early Gastric Cancer Presenting as a Submucosal Tumor. PMID- 27404968 TI - Uncertain Diagnostic Language Affects Further Studies, Endoscopies, and Repeat Consultations for Patients With Functional Gastrointestinal Disorders. AB - BACKGROUND & AIMS: Although guidelines state that functional gastrointestinal disorders (FGIDs) can be diagnosed with minimal investigation, consultations and investigations still have high costs. We investigated whether these are due to specific behaviors of specialist clinicians by examining differences in clinician approaches to organic gastrointestinal diseases vs FGIDs. METHODS: We performed a retrospective review of 207 outpatient department letters written from the gastroenterology unit at a tertiary hospital after patient consultations from 2008 through 2011. We collected data from diagnostic letters and case notes relating to patients with organic (n = 108) or functional GI disorders (n = 119). We analyzed the content of each letter by using content analysis and reviewed case files to determine which investigations were subsequently performed. Our primary outcome was the type of diagnostic language used and other aspects of the clinical approach. RESULTS: We found gastroenterologists to use 2 distinct types of language, clear vs qualified, which was consistent with their level of certainty (or lack thereof), for example, "the patient is diagnosed with...." vs "it is possible that this patient might have....". Qualified diagnostic language was used in a significantly higher proportion of letters about patients with FGIDs (63%) than organic gastrointestinal diseases (13%) (P < .001). In addition, a higher proportion of patients with FGIDs underwent endoscopic evaluation than patients with organic gastrointestinal diseases (79% vs 63%; P < .05). CONCLUSIONS: In an analysis of diagnoses of patients with FGIDs vs organic disorders, we found that gastroenterologists used more qualified (uncertain) language in diagnosing patients with FGIDs. This may contribute to patient discard of diagnoses and lead to additional, unwarranted endoscopic investigations. PMID- 27404969 TI - Clinical Relapse After Cessation of Tenofovir Therapy in Hepatitis B e Antigen Negative Patients. AB - BACKGROUND & AIMS: Of the hepatitis B e antigen-negative chronic hepatitis B patients with more than 1 year of sustained hepatitis B virus (HBV) suppression during therapy, the 1-year clinical relapse rate after cessation of entecavir therapy was 45%, of which 25.6% occurred within 6 months. The events after cessation of another preferred drug tenofovir were investigated. METHODS: A retrospective-prospective study was conducted in 85 hepatitis B e antigen negative chronic hepatitis B patients with sustained HBV suppression who had stopped tenofovir therapy and were monitored every 1 to 3 months for a median duration of 39 weeks (range, 4-133 wk). RESULTS: Clinical relapse occurred in 38 patients, 57.9% and 86.8% within 3 and 6 months, respectively, with an estimated 1-year cumulative incidence of 52%. The optimal duration of therapy and consolidation therapy were calculated to be 3 and 2 years, respectively. Of the relapsers, 81.6% and 57.9% showed an alanine aminotransferase level greater than 5 and 10 times the upper limit of normal, respectively, 23.7% showed a bilirubin level of 2 mg/dL or greater, and 2 developed hepatic decompensation. Relapsers had significantly higher pretherapy baseline hepatitis B surface antigen level, more prior anti-HBV therapy experience, later alanine aminotransferase level normalization, and a shorter duration of treatment and consolidation therapy. Cox regression analyses showed that treatment for more than 3 years combined with consolidation therapy for more than 2 years was an independent significant manageable factor of clinical relapse (adjusted hazard ratio, 0.387; P = .008). With this combination, the clinical relapse rate was reduced to 30%. CONCLUSIONS: Clinical relapses occurred mostly within 6 months, with high alanine aminotransferase and serum bilirubin levels. Closer monitoring, monthly in the first 3 to 6 months, with timely re-treatment is mandatory for a safe cessation of tenofovir therapy. PMID- 27404977 TI - Sociodemographic and access-related correlates of health-care utilization among African American injection drug users: The BESURE study. AB - Persons who inject drugs (PWID) may have less access to, and utilization of, health-care services, and African American PWID may be less likely than other racial groups to utilize health care in the United States. The present study evaluated the prevalence of health-care utilization (HCU) among a cohort of African American PWID in Baltimore. Data were from the 2012 Baltimore National HIV Behavioral Surveillance study. Participants were adult PWID and recruited using respondent-driven sampling (RDS). They completed a comprehensive sociobehavioral survey and voluntary HIV test with trained study interviewers. Analyses included descriptive and bivariate statistics to examine the prevalence of HCU, defined as seeing a health-care provider in the past year. Poisson regression assessed correlates of HCU. Participants were 61% male; 23% self reported HIV seropositivity. Nearly 90% reported unemployment and/or disability; HCU prevalence was 85%. Significant negative correlates of HCU included age and higher injection frequency; positive correlates included previous incarceration and moderate financial stability. Interaction analyses showed unemployed publicly insured individuals had 30% higher HCU than unemployed and uninsured individuals (chi2 = 2.52; p < .05). There is a need to improve health-care utilization among PWID. High prevalence of disability was still found, despite insurance coverage and access to care in this population. While the recent Affordable Care Act has increased health-care coverage and access, our results suggest that is only a first step to improving health outcomes among PWID; targeted intervention to integrate these individuals is still needed. PMID- 27404979 TI - T cell recall response of two hypothetical proteins (Rv2251 and Rv2721c) from Mycobacterium tuberculosis in healthy household contacts of TB - Possible subunit vaccine candidates. AB - The demonstrated variable efficacy of the only licensed TB vaccine Mycobacterium bovis bacillus Calmette-Guerin (M. bovis BCG) encourages the need for new vaccine candidates against TB. Antigen specific cellular immune response is often considered imperative during Mycobacterium tuberculosis (M. tuberculosis) infection and antigens that are strongly associated with the latent phase of infection are drawing increasing attention for anti-TB vaccine development. Here, we investigated the phenotypic and functional profiles of two novel mycobacterial antigens Rv2251 and Rv2721c during T cell recall response via multi-color flow cytometry. Healthy household contacts of TB (latent/HHC) and active pulmonary TB (PTB) patients were recruited to investigate the difference in antigen specific T cell recall response. These two antigens induced expansion of CD45RA- CCR7+ central memory subtypes and CD45RA- CCR7- effector memory cells in latent population which suggests their possible association with HHC. Rv2251 and Rv2721c antigen specific IFN-gamma, TNF-alpha and IL-2 response was also significantly high in HHC when compared to the PTB (p < 0.005, p < 0.05 and p < 0.05 respectively). The frequency of multifunctional T cells also was high in HHC compared to the PTB with statistical significance only for the antigen Rv2251. Often, the dominant Th1 immune response in HHC is correlated with the protection against the active TB disease. Collectively, we report the first insights into Rv2251 and Rv2721c antigen specific immune response in human donors of TB and provide the immunologic rationale for selecting them for vaccine development against TB. PMID- 27404978 TI - Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies. AB - OBJECTIVES: To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies. METHODS: We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case. RESULTS: CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremias. Independent risk factors for CRE BSI were prior beta-lactam/beta-lactamase inhibitor (adjusted odds ratio [aOR] 3.2; P = 0.03) or carbapenem (aOR 3.0; P = 0.05) use, current trimethoprim-sulfamethoxazole (aOR 24; P = 0.001) or glucocorticoid (aOR 5.4, P = 0.004) use, and having a prior CRE culture (aOR 12; P = 0.03). Patients with CRE bacteremia had a median of 52 h from culture collection until receipt of active therapy. They had a 51% BSI-related mortality rate, with a median of 4 days from bacteremia onset until death. CRE-active empirical therapy was associated with a lower 30-day mortality rate (17% vs. 59%; P = 0.08). CONCLUSIONS: CRE are lethal emerging causes of bacteremia in neutropenic patients. New strategies are needed to shorten the delay in administration of CRE active agents and improve outcomes in this vulnerable population. PMID- 27404980 TI - Highly Efficient Cuprous Complexes with Thermally Activated Delayed Fluorescence for Solution-Processed Organic Light-Emitting Devices. AB - Two mononuclear cuprous complexes [Cu(PNNA)(POP)]BF4 (1) and [Cu(PNNA)(Xantphos)]BF4 (2) (PNNA = 9,9-dimethyl-10-(6-(3-phenyl-1H-pyrazol-1 yl)pyridin-3-yl)-9,10-dihydroacridine, POP = bis[2 (dipenylphosphino)phenyl]ether, Xantphos =4,5-bis(diphenylphosphino)-9,9 dimethylxanthene), with intense bluish-green luminescence based on a new diimine ligand were designed and synthesized. Their structural, electrochemical, and photophysical properties were characterized by single-crystal X-ray analysis, cyclic voltammetry, temperature dependence of spectroscopy, time-dependent emission spectroscopy, etc. The complexes exhibit high photoluminescence quantum yields in doped films (up to 74.6%) at room temperature. Thermally activated delayed fluorescence based on intraligand charge transfer was observed by grafting a strong electron-donor moiety, 9,9-dimethylacridan, on the diimine ligand, which is supported by the density functional theory calculations on two complexes. Highly efficient solution-processed OLEDs based on these two complexes were fabricated, among which the electroluminescent device using 2 as dopant shows a peak external quantum efficiency of 7.42%, a peak current efficiency of 20.24 cd/A, and a maximum brightness of 5579 cd/m(2). PMID- 27404981 TI - Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9. AB - CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance. PMID- 27404982 TI - Distraction of Mental Arithmetic by Background Speech. AB - When solving mental arithmetic problems, one can easily be distracted by someone speaking in the background and this distraction is greater if the speech comprises numbers. We explored the basis of this disruption by asking participants to solve mental addition problems (e.g., "45 + 17 = ?") in three different conditions: background speech comprising numbers in ascending order (e.g., "61, 62, 63, 64, 65"), background speech comprising numbers in descending order (e.g., "65, 64, 63, 62, 61"), and quiet. Performance was best in quiet, worse in the descending numbers condition, and poorest in the ascending numbers condition. In view of these findings, we suggest that disruption arises as a by product of preventing the primed, but inaccurate, candidate responses from assuming the control of action. Alternative explanations are also discussed. PMID- 27404983 TI - In-Group Versus Out-Group Source Memory. AB - A common finding in the source monitoring literature is that greater similarity impairs source discriminability. Experiments traditionally manipulate similarity overtly by describing or showing sources with explicitly differentiable features. However, people may also infer source characteristics themselves, which should also affect discriminability. Two studies examined inferred source characteristics by capitalizing on the out-group homogeneity effect, whereby in group members are conceptualized as more diverse than out-group members. Participants learned about two sources who were described only as members of an in-group or an out-group and whose actions did not have higher a priori association with either group. Source memory was superior when participants believed the sources to be in-group members. This demonstrates that people spontaneously include inferred features with source representations and can capitalize on these features during source monitoring. Interestingly, information suggesting membership in one's in-group improved performance even for sources who had previously been considered out-group members (Experiment 2). PMID- 27404984 TI - Eye Movement Patterns Characteristic of Cognitive Style. AB - Various tools have been designed to classify the wholistic/analytic cognitive style, based mostly on behavioral data that reveals little about how these processes function. The main goal of this study is to characterize patterns of eye movements (EM) that are typical of learners with tendencies toward wholistic/analytic styles. Forty students completed the E-CSA-W/A test, while their EM were simultaneously monitored. The results revealed that the overall response time of the wholist group was lower in both tasks. The differences in response time between the groups are interpreted as being influenced by impulsive/reflective styles. While the behavioral data provide us with the end result and quantitative differences between the groups, EM provide us with the qualitative information about the process that led to the response. The study showed that the wholist group is characterized by less fixations and transitions than the analytic group, which is interpreted as reflecting use of whole/partial strategy. PMID- 27404985 TI - Mental Numerosity Line in the Human's Approximate Number System. AB - Previous studies have demonstrated existence of a mental line for symbolic numbers (e.g., Arabic digits). For nonsymbolic number systems, however, it remains unresolved whether a spontaneous spatial layout of numerosity exists. The current experiment investigated whether SNARC-like (Spatial-Numerical Association of Response Codes) effects exist in approximate processing of numerosity, as well as of size and density. Participants were asked to judge whether two serially presented stimuli (i.e., dot arrays, pentagons) were the same regarding numbers of dots, sizes of the pentagon, or densities of dots. Importantly, two confounds that were overlooked by most previous studies were controlled in this study: no ordered numerosity was presented, and only numerosity in the approximate number system (beyond the subitizing range) was used. The results demonstrated that there was a SNARC-like effect only in the numerosity-matching task. The results suggest that numerosity could be spontaneously aligned to a left-to-right oriented mental line according to magnitude information in human's approximate number system. PMID- 27404986 TI - Is the Emotional Dog Blind to Its Choices? AB - Previous choice blindness studies showed that people sometimes fail to notice when their choice is changed. Subsequently, they are willing to provide reasons for the manipulated choice which is the opposite of the one they made just seconds ago. In the present study, participants first made binary judgments about the wrongness of described behaviors and then were shown an opposite answer during a second reading of some of the descriptions. Half of the participants saw the answer during the second presentation of the description and the other half saw it only after the presentation. Based on Haidt's Social intuitionist model, we hypothesized that participants in the latter group would be less likely to reconcile their intuition with the presented answer and thus they would be more likely to reject it. However, we found no difference between the groups. PMID- 27404988 TI - Call for PapersExperimental Psychology. PMID- 27404987 TI - Spacing and Presentation Modes Affect the Unit-Decade Compatibility Effect During Number Comparison. AB - The unit-decade compatibility effect has challenged the model of holistic number magnitude processing, suggesting decomposed processing of multi-digit numbers. Recent evidence confirms that decomposed processing of decade and unit magnitudes occurs in parallel. However, the mode of presentation of multi-digit numbers may affect the processing mode (holistic vs. decomposed, parallel vs. sequential). We therefore investigated in two studies, whether presentation mode (vertical, horizontal, or consecutive) or the distance between two vertically presented numbers affects the unit-decade compatibility effect during number comparison. We found that the compatibility effect did not differ significantly between vertical and horizontal presentation, adding to previous results on perceptual generality, but was nonsignificant with consecutive presentation. However, the compatibility effect was significantly smaller, if numbers are spaced further apart. Thus, stimulus size and distance between numbers affect the processing of multi-digit numbers and should be reported in future studies. PMID- 27404989 TI - Perforating pseudoxanthoma elasticum with secondary elastosis perforans serpiginosa-like changes: dermoscopy, confocal microscopy and histopathological correlation. AB - Pseudoxanthoma elasticum is a rare congenital inherited elastolytic disorder that has sometimes been observed in association with transepidermal elimination of altered and calcified elastic fibers resulting in elastosis perforans serpiginosa like changes. In this case, histopathology is usually performed to rule out other conditions. The case of a 38-year-old woman with two slowly enlarging asymptomatic plaques occurring on the neck and surrounded by coalescing yellowish papules with a typical cobblestone appearance, evaluated by polarized light dermoscopy and reflectance confocal microscopy with histopathologic correlations, is described. Noteworthy, with reflectance confocal microscopy, the transepidermal elimination of the altered elastic fibers in the plaques was detected as hyperreflective material filling the dermal papillae, whereas the transversal cleavage of the calcified elastic fibers yielded a peculiar 'eggs-in the-basket' feature. PMID- 27404990 TI - Tempered mlo broad-spectrum resistance to barley powdery mildew in an Ethiopian landrace. AB - Recessive mutations in the Mlo gene confer broad spectrum resistance in barley (Hordeum vulgare) to powdery mildew (Blumeria graminis f. sp. hordei), a widespread and damaging disease. However, all alleles discovered to date also display deleterious pleiotropic effects, including the naturally occurring mlo-11 mutant which is widely deployed in Europe. Recessive resistance was discovered in Eth295, an Ethiopian landrace, which was developmentally controlled and quantitative without spontaneous cell wall appositions or extensive necrosis and loss of photosynthetic tissue. This resistance is determined by two copies of the mlo-11 repeat units, that occur upstream to the wild-type Mlo gene, compared to 11-12 in commonly grown cultivars and was designated mlo-11 (cnv2). mlo-11 repeat unit copy number-dependent DNA methylation corresponded with cytological and macroscopic phenotypic differences between copy number variants. Sequence data indicated mlo-11 (cnv2) formed via recombination between progenitor mlo-11 repeat units and the 3' end of an adjacent stowaway MITE containing region. mlo-11 (cnv2) is the only example of a moderated mlo variant discovered to date and may have arisen by natural selection against the deleterious effects of the progenitor mlo-11 repeat unit configuration. PMID- 27404991 TI - Impact of speciation on the electron charge transfer properties of nanodiamond drug carriers. AB - Unpassivated diamond nanoparticles (bucky-diamonds) exhibit a unique surface reconstruction involving graphitization of certain crystal facets, giving rise to hybrid core-shell particles containing both aromatic and aliphatic carbon. Considerable effort is directed toward eliminating the aromatic shell, but persistent graphitization of subsequent subsurface-layers makes perdurable purification a challenge. In this study we use some simple statistical methods, in combination with electronic structure simulations, to predict the impact of different fractions of aromatic and aliphatic carbon on the charge transfer properties of the ensembles of bucky-diamonds. By predicting quality factors for a variety of cases, we find that perfect purification is not necessary to preserve selectivity, and there is a clear motivation for purifying samples to improve the sensitivity of charge transfer reactions. This may prove useful in designing drug delivery systems where the release of (selected) drugs needs to be sensitive to specific conditions at the point of delivery. PMID- 27404992 TI - Multiple breath washout of hyperpolarized 129 Xe and 3 He in human lungs with three-dimensional balanced steady-state free-precession imaging. AB - PURPOSE: To compare quantitative fractional ventilation measurements from multiple breath washout imaging (MBW-I) using hyperpolarized 3 He with both spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) three-dimensional (3D) pulse sequences and to evaluate the feasibility of MBW-I with hyperpolarized 129 Xe. METHODS: Seven healthy subjects were scanned using 3 He MBW-I with 3D SPGR and bSSFP sequences. Five also underwent MBW-I with 129 Xe. A dual-tuned coil was used to acquire MBW-I data from both nuclei in the same subject position, enabling direct comparison of regional information. RESULTS: High-quality MBW images were obtained with bSSFP sequences using a reduced dose (100 mL) of inhaled hyperpolarized 3 He. 3D MBW-I with 129 Xe was also successfully demonstrated with a bSSFP sequence. Regional quantitative ventilation measures derived from 3 He and 129 Xe MBW-I correlated well in all subjects (P < 0.001) with mean Pearson's correlation coefficients of r = 0.61 and r = 0.52 for 3 He SPGR-bSSFP and 129 Xe-3 He (bSSFP) comparisons. The average intersubject mean difference (and standard deviation) in fractional ventilation in SPGR-bSSFP and 129 Xe-3 He comparisons was 15% (28%) and 9% (38%), respectively. CONCLUSIONS: Improved sensitivity in MBW-I can be achieved with polarization-efficient bSSFP sequences. Same scan-session 3D MBW-I with 3 He and 129 Xe has been demonstrated using a dual-tuned coil. Magn Reson Med 77:2288 2295, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID- 27404993 TI - Hydrogen peroxide, nitric oxide and UV RESISTANCE LOCUS8 interact to mediate UV-B induced anthocyanin biosynthesis in radish sprouts. AB - The cross talk among hydrogen peroxide (H2O2), nitric oxide (NO) and UV RESISTANCE LOCUS8 (UVR8) in UV-B-induced anthocyanin accumulation in the hypocotyls of radish sprouts was investigated. The results showed that UV-B irradiation significantly increased the anthocyanin accumulation and the expression of UVR8, and a similar trend appeared in radish sprouts subjected to cadmium, chilling and salt stresses regardless of light source. However, these responses disappeared under dark exposure. These results suggest that abiotic stress-induced anthocyanin accumulation and UVR8 expression were light-dependent. Moreover, abiotic stresses all enhanced the production of H2O2 and exogenous H2O2 addition significantly increased the anthocyanin concentration and UVR8 transcription, while these increases were severely inhibited by addition of dimethylthiourea (DMTU, a chemical trap for H2O2). It seems to suggest that H2O2 played an important role in the anthocyanin biosynthesis. Furthermore, addition of 0.5 mM sodium nitroprusside (SNP, a NO-releasing compound) substantially induced the anthocyanin accumulation, and H2O2-induced anthocyanin accumulation and UVR8 expression were significantly suppressed by co-treatment with 2-phenyl 4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO, a NO scavenger), which was parallel with the expression of anthocyanin biosynthesis-related transcription factors and structural genes. All these results demonstrate that both H2O2 and NO are involved in UV-B-induced anthocyanin accumulation, and there is a crosstalk between them as well as a classical UVR8 pathway. PMID- 27404997 TI - LUTs of blastocyst nuclei cell for quantification. PMID- 27404995 TI - Promoting 3-D Aggregation of FACS Purified Thymic Epithelial Cells with EAK 16 II/EAKIIH6 Self-assembling Hydrogel. AB - Thymus involution, associated with aging or pathological insults, results in diminished output of mature T-cells. Restoring the function of a failing thymus is crucial to maintain effective T cell-mediated acquired immune response against invading pathogens. However, thymus regeneration and revitalization proved to be challenging, largely due to the difficulties of reproducing the unique 3D microenvironment of the thymic stroma that is critical for the survival and function of thymic epithelial cells (TECs). We developed a novel hydrogel system to promote the formation of TEC aggregates, based on the self-assembling property of the amphiphilic EAK16-II oligopeptides and its histidinylated analogue EAKIIH6. TECs were enriched from isolated thymic cells with density-gradient, sorted with fluorescence-activated cell sorting (FACS), and labeled with anti epithelial cell adhesion molecule (EpCAM) antibodies that were anchored, together with anti-His IgGs, on the protein A/G adaptor complexes. Formation of cell aggregates was promoted by incubating TECs with EAKIIH6 and EAK16-II oligopeptides, and then by increasing the ionic concentration of the medium to initiate gelation. TEC aggregates embedded in EAK hydrogel can effectively promote the development of functional T cells in vivo when transplanted into the athymic nude mice. PMID- 27404994 TI - Development of a synthetic gene network to modulate gene expression by mechanical forces. AB - The majority of (mammalian) cells in our body are sensitive to mechanical forces, but little work has been done to develop assays to monitor mechanosensor activity. Furthermore, it is currently impossible to use mechanosensor activity to drive gene expression. To address these needs, we developed the first mammalian mechanosensitive synthetic gene network to monitor endothelial cell shear stress levels and directly modulate expression of an atheroprotective transcription factor by shear stress. The technique is highly modular, easily scalable and allows graded control of gene expression by mechanical stimuli in hard-to-transfect mammalian cells. We call this new approach mechanosyngenetics. To insert the gene network into a high proportion of cells, a hybrid transfection procedure was developed that involves electroporation, plasmids replication in mammalian cells, mammalian antibiotic selection, a second electroporation and gene network activation. This procedure takes 1 week and yielded over 60% of cells with a functional gene network. To test gene network functionality, we developed a flow setup that exposes cells to linearly increasing shear stress along the length of the flow channel floor. Activation of the gene network varied logarithmically as a function of shear stress magnitude. PMID- 27404998 TI - Hsp90 is involved in the entry of clostridial neurotoxins into the cytosol of nerve terminals. AB - Botulinum and tetanus neurotoxins are the most toxic substances known and form the growing family of clostridial neurotoxins. They are composed of a metalloprotease light chain (L), linked via a disulfide bond to a heavy chain (H). H mediates the binding to nerve terminals and the membrane translocation of L into the cytosol where their substrates, the three SNARE proteins, are localised. L translocation is accompanied by unfolding, and it has to be reduced and reacquire the native fold to exert its neurotoxicity. The Thioredoxin reductase-Thioredoxin system is responsible for the reduction, but it is unknown whether the refolding of L is spontaneous or aided by host chaperones. Here we report that geldanamycin, a specific inhibitor of heat shock protein 90, hampers the refolding of L after membrane translocation and completely prevents the cleavage of SNAREs. We also found that geldanamycin strongly synergises with PX 12, an inhibitor of thioredoxin, suggesting that the processes of L chain refolding and interchain disulfide reduction are strictly coupled. Indeed we found that the heat shock protein 90 and the Thioredoxin reductase-Thioredoxin system physically interact on synaptic vesicle where they orchestrate a chaperone redox machinery which is exploited by clostridial neurotoxins to deliver their catalytic part into the cytosol. PMID- 27404999 TI - Risk factors for genital human papillomavirus among men in Tanzania. AB - The objective of the study was to assess risk factors for Human Papillomavirus (HPV) among men in Tanzania, both overall and in relation to HIV status. In a cross-sectional study conducted among 1,813 men in Tanzania, penile swabs were tested for HPV using Hybrid Capture 2 (HC2). Study participants were offered HIV testing. Risk factors for HPV (HC2 high-risk and/or low-risk positivity) were assessed using logistic regression with adjustment for age, lifetime number of sexual partners, and HIV status. Altogether, 372 men (20.5%) were HPV-positive. Among men tested for HIV (n = 1,483), the HIV prevalence was 9.4%. The odds ratio (OR) of HPV increased with increasing age. HIV-positivity was associated with an increased odds ratio of HPV (OR = 1.91; 95%CI: 1.30-2.82), whereas the odds of HPV tended to be lower in circumcised men than in uncircumcised men (OR = 0.77; 95%CI: 0.54-1.09). When stratifying by HIV status, we found lower odds of HPV in overweight HIV-positive men (BMI > 25) than in normal weight HIV-positive men (OR = 0.25; 95%CI: 0.08-0.78). This did not apply to HIV-negative men. Circumcision tended to decrease the odds of HPV both in HIV-positive men and in HIV-negative men, although not being statistically significant. In conclusion, HIV is a strong risk factor for HPV among men in Tanzania. Additionally, in HIV-positive men a high BMI seems to be associated with a lower risk of HPV. Finally, we observed a tendency toward a lower risk of HPV both among HIV-positive and HIV-negative circumcised men compared to their uncircumcised counterparts. J. Med. Virol. 89:345-351, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27405000 TI - Access to C4-Functionalized Quinolines via Copper-Catalyzed Tandem Annulation of Alkynyl Imines with Diazo Compounds. AB - An efficient synthesis of C4-functionalized quinolines through copper-catalyzed tandem annulation of alkynyl imines with diazo compounds is described. This transformation involves an in situ formation of allene and intramolecular electrocyclization, which features high efficiency, mild reaction conditions, easy operation, and broad functional-group tolerance. A wide variety of C4 functionalized quinolines were provided in up to 92% yield for 33 examples. PMID- 27405001 TI - Understanding the Behavior of Systems Pharmacology Models Using Mathematical Analysis of Differential Equations: Prolactin Modeling as a Case Study. AB - In this tutorial, we introduce basic concepts in dynamical systems analysis, such as phase-planes, stability, and bifurcation theory, useful for dissecting the behavior of complex and nonlinear models. A precursor-pool model with positive feedback is used to demonstrate the power of mathematical analysis. This model is nonlinear and exhibits multiple steady states, the stability of which is analyzed. The analysis offers insight into model behavior and suggests useful parameter regions, which simulations alone could not. PMID- 27405002 TI - Convergence of the Many-Body Expansion for Energy and Forces for Classical Polarizable Models in the Condensed Phase. AB - We analyze convergence of energies and forces for the AMOEBA classical polarizable model when evaluated as a many-body expansion (MBE) against the corresponding N-body parent potential in the context of a condensed-phase water simulation. This is in contrast to most MBE formulations based on quantum mechanics, which focus only on convergence of energies for gas-phase clusters. Using a single water molecule as a definition of a body, we find that truncation of the MBE at third order, 3-AMOEBA, captures direct polarization exactly and yields apparent good convergence of the mutual polarization energy. However, it renders large errors in the magnitude of polarization forces and requires at least fourth-order terms in the MBE to converge toward the parent potential gradient values. We can improve the convergence of polarization forces for 3 AMOEBA by embedding the polarization response of dimers and trimers within a complete representation of the fixed electrostatics of the entire system. We show that the electrostatic embedding formalism helps identify the specific configurations involving linear hydrogen-bonding arrangements that are poorly convergent at the 3-body level. By extending the definition of a body to be a large water cluster, we can reduce errors in forces to yield an approximate polarization model that is up to 10 times faster than the parent potential. The 3 AMOEBA model offers new ways to investigate how the properties of bulk water depend on the degree of connectivity in the liquid. PMID- 27405003 TI - Methyl Radical in Clathrate Silica Voids. The Peculiar Physisorption Features of the Guest-Host Molecular Dynamics Interaction. AB - EPR line shape simulations of CH3/SiO2 clathrates and comparison to CH3/N2O and CH3/SiO2 experiments reveal the motional conditions of the CH3 radical up to the unusual regime of its stability, the high-temperature diffusional regime, at 300 K. In the low-temperature region, the CH3 in clathrates is found to rotate around the in-plane axes even at as low temperatures as 3.8 K. However, nonrotating methyls performing only libration about the C2-axes as well as around the C3-axis are also found, proving the existence of special sites in the clathrate voids that begin to accumulate a significant fraction of methyl radicals at temperatures below approximately 7 K. A distinctive feature in the spectrum anisotropy and line width temperature profiles is found nearby 25 K, which is interpreted as the radical physisorption inside the voids that occurs with the sample temperature lowering. The unusual increase of the CH3/SiO2 clathrate EPR spectral width with temperature over approximately 120 K has its origin in repeated angular momentum vector alterations due to frequent collisions with the clathrate void walls between periodical free rotation periods. This relaxation mechanism resembles to spin-rotation interaction known only for small molecular species in nonviscous fluids but unknown earlier for methyl hosted in solids. PMID- 27405004 TI - Square-Planar Alkylidyne-Osmium and Five-Coordinate Alkylidene-Osmium Complexes: Controlling the Transformation from Hydride-Alkylidyne to Alkylidene. AB - Square-planar alkylidyne and five-coordinate alkylidene mixed (i)Pr3P-Os-IPr (IPr = 1,3-bis(diisopropylphenyl)imidazolylidene) complexes have been discovered and characterized, and their formation has been rationalized. The cationic five coordinate hydride-alkylidyne compounds [OsHX(=CPh)(IPr)(P(i)Pr3)]OTf (X = Cl (1), F (4); OTf = CF3SO3) undergo deprotonation with KO(t)Bu to afford the trans halide-alkylidyne square-planar derivatives OsX(=CPh)(IPr)(P(i)Pr3) (X = Cl (2), F (5)). Oxidative addition of the C(sp)-H bond of phenylacetylene and methyl propiolate along the Cl-Os-CPh axis of 2 with the hydrogen atom directed to the alkylidyne leads to alkynyl-cis-hydride-alkylidyne intermediates, which rapidly evolve into the five-coordinate alkylidene complexes Os(C=CR)Cl(?CHPh)(IPr)(P(i)Pr3) (R = Ph (6), CO2Me (7)) as a consequence of the migration of the hydride from the metal center to the Calpha atom of the alkylidyne. Oxidative addition of the C(sp)-H bond of methyl propiolate along the X-Os-CPh axis of 2 and 5 with the hydrogen atom directed to the halide gives the alkynyl-trans-hydride-alkylidyne derivatives OsH(C=CCO2Me)X(=CPh)(IPr)(P(i)Pr3) (X = Cl (8), F (9)). Complex 8 evolves into 7. However, complex 9 containing the stronger pi-donor fluoride is stable. The oxidative addition of HCl to 2 selectively yields the cis-hydride-alkylidyne compound OsHCl2(=CPh)(IPr)(P(i)Pr3) (10), which is also stable. PMID- 27405005 TI - Identifying protein complexes based on brainstorming strategy. AB - Protein complexes comprising of interacting proteins in protein-protein interaction network (PPI network) play a central role in driving biological processes within cells. Recently, more and more swarm intelligence based algorithms to detect protein complexes have been emerging, which have become the research hotspot in proteomics field. In this paper, we propose a novel algorithm for identifying protein complexes based on brainstorming strategy (IPC-BSS), which is integrated into the main idea of swarm intelligence optimization and the improved K-means algorithm. Distance between the nodes in PPI network is defined by combining the network topology and gene ontology (GO) information. Inspired by human brainstorming process, IPC-BSS algorithm firstly selects the clustering center nodes, and then they are separately consolidated with the other nodes with short distance to form initial clusters. Finally, we put forward two ways of updating the initial clusters to search optimal results. Experimental results show that our IPC-BSS algorithm outperforms the other classic algorithms on yeast and human PPI networks, and it obtains many predicted protein complexes with biological significance. PMID- 27405006 TI - Drug-Induced Akathisia in Children and Adolescents. PMID- 27405007 TI - RNA interference of a trehalose-6-phosphate synthase gene reveals its roles during larval-pupal metamorphosis in Bactrocera minax (Diptera: Tephritidae). AB - Trehalose is the major blood sugar in insects, which plays a crucial role as an instant source of energy and the starting substrate for chitin biosynthesis. In insects, trehalose is synthesized by catalysis of an important enzyme, trehalose 6-phosphate synthase (TPS). In the present study, a trehalose-6-phosphate synthase gene from Bactrocera minax (BmTPS) was cloned and characterized. BmTPS contained an open reading frame of 2445 nucleotides encoding a protein of 814 amino acids with a predicted molecular weight of 92.05kDa. BmTPS was detectable in all developmental stages of Bactrocera minax and expressed higher in the final (third-) instar larvae. Tissue-specific expression patterns of BmTPS showed that it was mainly expressed in the fat body. The 20-hydroxyecdysone (20E) induced the expression of BmTPS and three genes in the chitin biosynthesis pathway. Moreover, injection of double-stranded RNA into third-instar larvae successfully silenced the transcription of BmTPS in B. minax, and thereby decreased the activity of TPS and trehalose content. Additionally, silencing of BmTPS inhibited the expression of three key genes in the chitin biosynthesis pathway and exhibited 52% death and abnormal phenotypes. The findings demonstrate that BmTPS is indispensable for larval-pupal metamorphosis. Besides, the establishment of RNAi experimental system in B. minax would lay a solid foundation for further investigation of molecular biology and physiology of this pest. PMID- 27405008 TI - In vivo real-time monitoring of aphrodisiac pheromone release of small white cabbage butterflies (Pieris rapae). AB - The study of insect behavior is of practical importance for developing possible control methods in Integrated Pest Management. Currently, one model of butterfly mating behavior suggests that the initial location of potential mates occurs visually followed by the release of one or more short-range male aphrodisiac pheromones. This model is supported by data obtained from field observations and inferences based on the behavioral effects of chemicals extracted or isolated using indirect and offline techniques. In this study, we performed in vivo real time monitoring of the male aphrodisiac pheromones released by the small white cabbage male butterfly (Pieris rapae Linnaeus) using confined direct analysis in real time (cDART) mass spectrometry. cDART is a new method easily adapted to the study in real time of chemicals released into the environment by virtually any insect. The major compound released by the male Pieris rapae was identified as ferrulactone. The experimental results reported here indicate that the release of ferrulactone occurs less than 1s after the male visualizes its partner, and reaches a maximum after about one half minute. This study is the first reported in vivo detection and monitoring of butterfly male aphrodisiac pheromones in real time. PMID- 27405009 TI - Balanced intake of protein and carbohydrate maximizes lifetime reproductive success in the mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae). AB - Recent developments in insect gerontological and nutritional research have suggested that the dietary protein:carbohydrate (P:C) balance is a critical determinant of lifespan and reproduction in many insects. However, most studies investigating this important role of dietary P:C balance have been conducted using dipteran and orthopteran species. In this study, we used the mealworm beetles, Tenebrio molitor L. (Coleoptera: Tenebrionidae), to test the effects of dietary P:C balance on lifespan and reproduction. Regardless of their reproductive status, both male and female beetles had the shortest lifespan at the protein-biased ratio of P:C 5:1. Mean lifespan was the longest at P:C 1:1 for males and at both P:C 1:1 and 1:5 for females. Mating significantly curtailed the lifespan of both males and females, indicating the survival cost of mating. Age specific egg laying was significantly higher at P:C 1:1 than at the two imbalanced P:C ratios (1:5 or 5:1) at any given age throughout their lives, resulting in the highest lifetime reproductive success at P:C 1:1. When given a choice, beetles actively regulated their intake of protein and carbohydrate to a slightly carbohydrate-biased ratio (P:C 1:1.54-1:1.64 for males and P:C 1:1.3 1:1.36 for females). The self-selected P:C ratio was significantly higher for females than males, reflecting a higher protein requirement for egg production. Collectively, our results add to a growing body of evidence suggesting the key role played by dietary macronutrient balance in shaping lifespan and reproduction in insects. PMID- 27405010 TI - Melanin pigmentation gives rise to black spots on the wings of the silkworm Bombyx mori. AB - Several mutants of the silkworm Bombyx mori show body color variation at the larval and adult stages. The Wild wing spot (Ws) mutant exhibits a phenotype in which the moth has a spot on the apex of the forewing. In this study, we investigated this trait to elucidate the molecular mechanism underlying the color pattern. Microscopy of the black spot of Ws mutants showed that the pigment emerges in the scales of the wing, and accumulation of the pigment becomes strong just before eclosion. We next examined the relationship between the black spot of the Ws mutant and melanin. The spectrophotometry using alkaline extracts from the black spot in the wing showed the highest absorption intensity at 405nm, which is the absorbance wavelength of melanin. Moreover, inhibition assays for enzymes implicated in melanin synthesis using 3-iodo-l-tyrosine (a tyrosine hydroxylase inhibitor) and L-alpha-methyl-DOPA (a dopa decarboxylase inhibitor) revealed that treatment with each inhibitor disrupted the pigmentation of the wing of the Ws mutant. On the basis of these results, we analyzed the expression pattern of five genes involved in melanin formation, and found that the expression levels of yellow and laccase2 were increased just before pigmentation, whereas those of DDC, tan, and TH were increased when the apex of the wing turned black. These results showed that melanin pigmentation gives rise to the black spot on the wing. PMID- 27405012 TI - Hypomyelinating Leukodystrophy due to HSPD1 Mutations: A New Patient. AB - The hypomyelinating leukodystrophies (HMLs) encompass the X-linked Pelizaeus Merzbacher disease (PMD) caused by PLP1 mutations and known as the classical form of HML as well as Pelizaeus-Merzbacher-like disease (PMLD) (Online Mendelian Inheritance in Man [OMIM] 608804 and OMIM 260600) due to GJC2 mutations. In addition, mutations in at least 10 other genes are known to cause HMLs. In 2008, an Israeli family with clinical and neuroimaging findings similar to those found in PMD was reported. The patients were found to have a homozygous missense mutation in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60), and the disorder was defined as the autosomal recessive mitochondrial Hsp60 chaperonopathy (MitCHAP-60) disease. We here report the first case of this severe neurodegenerative disease since it was first described. Given the fact that the families carried the same mutation our patient probably belongs to the same extended family as the Israeli family. In conclusion, the MitCHAP-60 disease should be considered as a rare differential diagnosis in HML. PMID- 27405011 TI - Multi-functionality Redefined with Colloidal Carotene Carbon Nanoparticles for Synchronized Chemical Imaging, Enriched Cellular Uptake and Therapy. AB - Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C(3)-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C(3)-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of beta-carotene. Surface coating of C(3) with phospholipid was used to generate C(3)-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies. PMID- 27405013 TI - Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad-Spectrum Antiproliferative Activity. AB - Herein we report the discovery of compound 6 [KST016366; 4-((2-(3-(4-((4 ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)ureido)benzo[d]thiazol-6 yl)oxy)picolinamide] as a new potent multikinase inhibitor through minor structural modification of our previously reported RAF kinase inhibitor A. In vitro anticancer evaluation of 6 showed substantial broad-spectrum antiproliferative activity against 60 human cancer cell lines. In particular, it showed GI50 values of 51.4 and 19 nm against leukemia K-562 and colon carcinoma KM12 cell lines, respectively. Kinase screening of compound 6 revealed its nanomolar-level inhibitory activity of certain oncogenic kinases implicated in both tumorigenesis and angiogenesis. Interestingly, 6 displays IC50 values of 0.82, 3.81, and 53 nm toward Tie2, TrkA, and ABL-1 (wild-type and T315I mutant) kinases, respectively. Moreover, 6 is orally bioavailable with a favorable in vivo pharmacokinetic profile. Compound 6 may serve as a promising candidate for further development of potent anticancer chemotherapeutics. PMID- 27405014 TI - Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma. AB - The diagnosis of malignant pleural mesothelioma (MPM) is challenging and requires immunohistochemistry or electron microscopy assays to specifically differentiate MPM from lung adenocarcinoma. An ultrastructural study of fresh tissue is considered to be the "gold standard." In most cases, the first diagnostic approach is performed on pleural effusion, and in some patients, this is the only available sample for diagnosis. The aim of the present study is to evaluate if an examination of pleural effusion samples based on electron microscopy (EMpe) is a useful tool for the differential diagnosis of MPM and lung adenocarcinoma. An EMpe study was performed in 25 pleural effusion samples. Histological and immunohistochemical markers confirmed the diagnosis of either mesothelioma (5) or adenocarcinoma (20). Of the five cases that were diagnosed with mesothelioma, two samples (40%) showed cells with "bushy" microvilli, which are characteristic of mesothelioma, by EMpe, and three were acellular (60%). Of the 20 cases of adenocarcinoma, EMpe showed cells with short microvilli in 9 (45%), and 11 were acellular (55%). EMpe identifies unequivocal morphological changes that are useful for the differential diagnosis of MPM or adenocarcinoma when the pleural effusion sample contains evaluable tumor cells. PMID- 27405015 TI - High Resolution Phonon-assisted Quasi-resonance Fluorescence Spectroscopy. AB - High resolution optical spectroscopy methods are demanding in terms of either technology, equipment, complexity, time or a combination of these. Here we demonstrate an optical spectroscopy method that is capable of resolving spectral features beyond that of the spin fine structure and homogeneous linewidth of single quantum dots (QDs) using a standard, easy-to-use spectrometer setup. This method incorporates both laser and photoluminescence spectroscopy, combining the advantage of laser line-width limited resolution with multi-channel photoluminescence detection. Such a scheme allows for considerable improvement of resolution over that of a common single-stage spectrometer. The method uses phonons to assist in the measurement of the photoluminescence of a single quantum dot after resonant excitation of its ground state transition. The phonon's energy difference allows one to separate and filter out the laser light exciting the quantum dot. An advantageous feature of this method is its straight forward integration into standard spectroscopy setups, which are accessible to most researchers. PMID- 27405017 TI - In-Depth Analysis of Computer Memory Acquisition Software for Forensic Purposes. AB - The comparison studies on random access memory (RAM) acquisition tools are either limited in metrics or the selected tools were designed to be executed in older operating systems. Therefore, this study evaluates widely used seven shareware or freeware/open source RAM acquisition forensic tools that are compatible to work with the latest 64-bit Windows operating systems. These tools' user interface capabilities, platform limitations, reporting capabilities, total execution time, shared and proprietary DLLs, modified registry keys, and invoked files during processing were compared. We observed that Windows Memory Reader and Belkasoft's Live Ram Capturer leaves the least fingerprints in memory when loaded. On the other hand, ProDiscover and FTK Imager perform poor in memory usage, processing time, DLL usage, and not-wanted artifacts introduced to the system. While Belkasoft's Live Ram Capturer is the fastest to obtain an image of the memory, Pro Discover takes the longest time to do the same job. PMID- 27405018 TI - Human Identification Using Automatic and Semi-Automatically Detected Facial Marks. AB - Continuing advancements in the field of digital cameras and surveillance imaging devices have led law enforcement and intelligence agencies to use analysis of images and videos for the investigation and prosecution of crime. When determining identity from photographic evidence, forensic analysts perform comparison of visible facial features manually, which is inefficient. In this study, we will address research efforts to use facial marks as biometric signatures to distinguish between individuals. We propose two systems to assist forensic analysts during photographic comparison: an improved multiscale facial mark system in which facial marks are detected automatically, and a semi automatic facial mark system that integrates human knowledge within the improved multiscale facial mark system. Experiment results employ a high-resolution time elapsed dataset acquired at the University of Notre Dame between 2009 and 2011. The results indicate that the geometric distributions of facial mark patterns can be used to distinguish between individuals. PMID- 27405019 TI - A Long-term Study of the Association between the Relative Poverty Rate and Suicide Rate in Japan. AB - The annual number of suicides in Japan totaled around 23,000 in 1997 and abruptly increased to around 31,000 in 1998. This figure has remained high since then. This abrupt increase in the number of suicides was primarily due to an increase in suicides occasioned by economic concerns. The association between various economic factors and suicide must be studied in detail and over the long term in order to ascertain the association between economic concerns and suicide. This study examined the relative poverty rate and the suicide rate in Japan over 30 years and discussed the association between those two rates. The results suggest that the relative poverty rate may be associated with the suicide rate for both sexes. This association is true for men in particular. The organizations and professionals involved in implementing suicide prevention measures should be cognizant of the current findings and consider formulating additional specific measures. PMID- 27405020 TI - Malingering by Proxy: A Literature Review and Current Perspectives. AB - Malingering by proxy (MAL-BP) is a form of maltreatment that involves a caregiver who fabricates or induces signs or symptoms in a child, dependent adult, or pet in pursuit of external, tangible incentives. Rarely studied, MAL-BP has an unknown prevalence, and is a challenging diagnosis for healthcare professionals. Therefore, a comprehensive computer literature search and review was conducted. The review uncovered a total of sixteen case reports of MAL-BP (eleven human, five veterinary). The motive for malingering was financial in all human cases and medication-seeking in all veterinary cases. Although the strategies employed differed among the identified cases, common themes regarding the best approach to identification of MAL-BP cases became evident. A comprehensive workup including a thorough history, physical examination, appropriate neuropsychological testing, and relevant collateral information forms the basis of an effective identification strategy. The optimal method of management is currently unclear due to a relative paucity of data and guidelines. However, management of these cases would likely include a team-based approach with a prudent assessment of safety for the proxy and a low threshold for referral to appropriate services. Long-term follow-up is essential and should be approached from a biopsychosocial perspective. Attention, research, and guidance on this topic are needed to develop further evidence-based guidelines for the identification and management of MAL-BP. PMID- 27405021 TI - Identification and Individualization of Lophophora using DNA Analysis of the trnL/trnF Region and rbcL Gene. AB - Lophophora williamsii (peyote) is a small, spineless, greenish-blue cactus found in Mexico and the southwestern United States. Ingestion of the cactus can result in hallucinations due to its content of mescaline. In the United States, L. williamsii is classified as a Schedule I controlled substance. In this study, we use DNA analysis of the chloroplast trnL/trnF region and chloroplast rbcL gene to identify the individuals of Lophophora. Using the rbcL gene, Lophophora specimens could be distinguished from outgroups, but species within the genus could not be distinguished. The trnL/trnF region split the Lophophora genus into several groups based on the length and substructure of an AT-rich segment of the sequence. Our results indicate that the genetic variability at the trnL/trnF locus is greater than previously recognized. Although DNA structures at the trnL/trnF region and rbcL gene do not align with the classification of Lophophora species, they can be used to aid in forensic analysis. PMID- 27405022 TI - Distinguishing Between Legally and Illegally Produced Gold in South Africa. AB - The identification of gold-bearing material is essential for combating the theft of gold in South Africa. Material seized in police operations is generally a mixture of gold from different mines, and as such cannot be traced back to a single location. ICP-OES analysis of material dissolved by acid dissolution provided a database of gold compositions comprising gold from South African mines, illegal gold stolen from the mines, and commercial gold alloys and jewelery. Discrimination between legal and illegal gold was possible due to the presence of Pb, As, Sb, Sn, Se, and Te in the stolen material, elements which are not present in legally produced gold. The presence of these elements is a quick and simple way to distinguish between gold alloys based on refined gold, such as in commercially manufactured jewelery, and gold alloys containing a proportion of unrefined and therefore illegally obtained gold. PMID- 27405023 TI - Auricular Surface Aging: Comparing Two Methods that Assess Morphological Change in the Ilium with Bayesian Analyses. AB - Modern standards in forensic anthropology require rigorous testing and evaluation of methods used for aging skeletal remains. Age estimation has been criticized for bias, inaccuracy, and population specificity; issues which are minimized by the application of Bayesian methodology. Using Bayesian statistics, we compare the Lovejoy et al. (Am J Phys Anthropol, 68, 1985, 15) (original) and Buckberry and Chamberlain (Am J Phys Anthropol, 119, 2002, 231) (revised) auricular surface aging methods. Transition analysis parameters derived from American males (n = 372), in combination with a Thai male (N = 37) informative prior, statistically model age in Portuguese males (n = 221). Cumulative binomial tests assess the accuracy of the generated age ranges. Overall, the application of transition analysis and Bayesian statistics significantly improved age estimation with both methods (also outperforming Suchey-Brooks pubic symphysis aging). Moreover, the accuracy of the original method was low without statistical modeling, whereas the revised method can be applied accurately without further statistical analysis. Additionally, reference tables for aging Portuguese males are provided. PMID- 27405024 TI - Cholinesterase-based biosensors. AB - Recently, cholinesterase-based biosensors are widely used for assaying anticholinergic compounds. Primarily biosensors based on enzyme inhibition are useful analytical tools for fast screening of inhibitors, such as organophosphates and carbamates. The present review is aimed at compilation of the most important facts about cholinesterase based biosensors, types of physico chemical transduction, immobilization strategies and practical applications. PMID- 27405025 TI - 68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer. AB - A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases. PMID- 27405026 TI - Paget Disease: A Potential Pitfall in PSMA PET for Prostate Cancer. AB - We present a case of an 81-year-old man with multifocal Paget disease found on bone scan that was performed for incidentally diagnosed prostate cancer. The subsequent Ga-PSMA (HBED-CC) PET scan also displayed increased uptake in the same distribution. Multiple known tumors display increased Ga-PSMA uptake due to neovasculature. We postulate that increased Ga-PSMA uptake within the pagetoid bone relates to neovascularity known to occur in Paget disease. Such pagetic uptake could result in false-positive studies for bone metastases, particularly in the setting of less typical Paget disease. PMID- 27405027 TI - Intense 18F-FDG Uptake in Chronic Subcutaneous Opioid Injection Sites. AB - Subcutaneous F-FDG uptake is a common finding on PET scans, with causes including both benign and malignant conditions. Often, the pattern of uptake or the clinical indication for the PET scan will suggest the etiology. However, unusual or unexpected patterns may require careful clinical history. We report the case of a 45-year-old woman who underwent a PET/CT study for paraneoplastic syndrome evaluation and was found to have intense, extensive, bilaterally symmetric, nodular subcutaneous FDG uptake in the lower back and buttocks that was related to long-term repeated subcutaneous opioid injections. PMID- 27405028 TI - 18F-NaF PET/CT Images of Cardiac Metastasis From Osteosarcoma. AB - Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Cardiac osteosarcoma metastasis is rare. We described a 17-year-old boy who had right distal femoral osteosarcoma with lung metastases. During follow-up, right ventricular (RV) metastasis was noted and confirmed by histopathological examination of the surgical specimen. F-NaF PET/CT was then arranged 1 month after debulking surgery for residual tumor survey. The images showed intense F NaF uptake at RV region, suggestive of residual cardiac metastases. PMID- 27405029 TI - Chronic Nonbacterial Osteomyelitis With FDG Avid Rib Destruction and Extensive Lymphadenopathy. AB - Chronic nonbacterial osteomyelitis is a rare entity of unknown etiology and most likely an autoinflammatory disease. A 45-year-old man complained of a growing painful mass of the right chest wall. FDG PET/CT demonstrated a large destructive rib lesion with intense uptake and extensive FDG avid lymphadenopathy, which mimicked a malignant or metastatic disease. Both CT guided core-needle and excisional biopsies showed reactive/regenerative/granulomatous changes coupled with focal neutrophils and marrow atrophy, consistent with chronic osteomyelitis. Stains and cultures of surgical and wound specimens and multiple blood cultures were all negative for any kind of microorganism. PMID- 27405030 TI - Re: Initial Experience of 18F-FDG PET/MRI in Thymic Epithelial Tumors: Morphologic, Functional, and Metabolic Biomarkers. PMID- 27405031 TI - FDG PET/CT Imaging of Calcified Sister Mary Joseph Nodule. AB - Sister Mary Joseph nodule (SMJN) refers to any metastatic deposit in the periumbilical region. Herein, we report a very rare case of calcified SMJN from ovarian papillary serous adenocarcinoma showing intense FDG uptake. PMID- 27405032 TI - Juvenile Psammomatoid Ossifying Fibroma: Findings on Bone Scan. AB - Juvenile psammomatoid ossifying fibroma is a rare bone-forming tumor seen in craniofacial bones, which affects mainly young patients. We report scintigraphic and SPECT/CT findings of 2 patients diagnosed with this disease. One patient presented with suspicion of fibrous dysplasia and the other with suspected malignancy in the setting of a rapidly growing mass. Both cases highlight the importance of recognizing this type of tumor in young patients with abnormal uptake in paranasal bones and sinuses within the range of potential differential diagnoses including sarcomas, fibrous dysplasia, and odontogenic tumors. PMID- 27405033 TI - "Bottle Brush Sign"-Spinal Meningeal Disease on 18F-FDG PET-CT Scan. AB - A 30-year-old man with a history of stage IV AE diffuse large cell lymphoma of left proximal humerus presented with new onset lower limb weakness at completion of chemotherapy. The F-FDG PET-CT scan showed increased intraspinal uptake from T12 to S1 vertebrae with unique "bottle brush" appearance in keeping with spinal meningeal disease. The leptomeningeal disease was further confirmed on correlative MRI scan. PMID- 27405034 TI - Gallbladder Activity on 99mTc-Labeled Red Cell Scintigraphy Confirmed by SPECT/CT Imaging. AB - Tc-labeled red cell (Tc-RBC) scintigraphy is commonly used to detect gastrointestinal bleeding. Gallbladder visualization on Tc-RBC scintigraphy is not common. We present a case of gallbladder visualization on Tc-RBC scintigraphy confirmed by SPECT/CT imaging in a patient with chronic renal failure and anemia. PMID- 27405035 TI - Incidental Warthin Tumor on Pertechnetate Scintigraphy. AB - A 30-year-old woman underwent Tc-pertechnetate scintigraphy for evaluation of thyrotoxicosis. The scintigraphy revealed hypervascular thyroid gland with markedly increased trapping function in both the lobes suggesting diagnosis of Graves disease. Incidentally, a hypervascular and pertechnetate avid focus was seen along the lateral margin of the right parotid gland. Pertechnetate avidity and site of uptake suggested possibility of Warthin tumor. Clinical examination and ultrasonography revealed a well-defined lesion in the superficial lobe of the right parotid gland favoring diagnosis of benign lesion. Postsurgery specimen confirmed diagnosis of Warthin tumor. PMID- 27405036 TI - Zosteriform Secondary Cutaneous Diffuse Large B-Cell Lymphoma on FDG PET/CT. AB - We present a case of a woman who had erythematous papules on the abdomen accompanied with numbness and local heat sensation. She had received chemotherapy for advanced follicular lymphoma. F-FDG PET/CT demonstrated band-like hypermetabolic lesions seemingly involving dermatomes of lower abdominal wall, which was confirmed as secondary cutaneous diffuse large B-cell lymphoma via skin biopsy. PMID- 27405037 TI - Reinforcing the Ability of 99mTcO4 Scintigraphy for Identifying Differentiated Thyroid Cancer by TSH Stimulation. AB - Although radioiodines are widely used to localize metastatic differentiated thyroid cancer (DTC), TcO4 also can be used because it is a substrate for the sodium-iodide symporter protein. The use of TcO4 has advantages over radioiodine, namely, easy availability, dispensability of iodine restriction, and early imaging time. However, its low sensitivity precludes its practical application. Scintigraphic detectability of DTC using sodium-iodide symporter substrates is related to the serum TSH levels. Here, I report a case with multiple metastatic lesions of DTC that were detected upon TSH-stimulated TcO4 scintigraphy, but not with non-TSH-stimulated scintigraphy using the same tracer. PMID- 27405038 TI - FDG PET/MRI Imaging of an Angiosarcoma in a Popliteal Aneurysm and Tibial Head After Popliteal Graft. AB - Angiosarcomas are rare aggressive neoplasms with a wide variety of anatomic locations, one third of them presenting multifocal. Molecular imaging with PET/CT and PET/MR plays an emerging role in staging sarcomas. This case demonstrates the value of PET/MR imaging of an angiosarcoma with involvement of the tibial head and a popliteal aneurysm with histopathologic correlation. PMID- 27405039 TI - Schwannoma Showing Avid Uptake on 68Ga-PSMA-HBED-CC PET/CT. AB - Ga prostate-specific membrane antigen (PSMA) PET/CT is a relatively new and highly sensitive imaging modality used in staging metastatic prostate cancer. We report a case of a 65-year-old man with newly diagnosed prostate carcinoma who had a PSMA PET/CT scan for staging of his disease. A PSMA-avid right pelvic mass was identified anterior to the sacrum. Surgical removal and histopathological examination of this lesion revealed the diagnosis of schwannoma. It is important to be aware that schwannoma may also show avid uptake on PSMA PET/CT scan and may potentially lead to an incorrect diagnosis of metastatic prostate carcinoma. PMID- 27405040 TI - The Uptake of 18F-FDG by Renal Allograft in Kidney Transplant Recipients Is Not Influenced by Renal Function. AB - PURPOSE OF THE REPORT: F-FDG PET/CT has been recently proposed as a noninvasive tool for the diagnosis of renal allograft acute rejection (AR) in kidney transplant recipients (KTRs). Still, the influence of kidney function on F-FDG uptake by renal grafts remains unknown. PATIENTS AND METHODS: We retrospectively identified all KTRs who underwent at least one F-FDG PET/CT. Kidney transplant recipients with documented pyelonephritis or AR were excluded. Estimated glomerular filtration rate (eGFR) was assessed using chronic kidney disease (CKD) EPI equation. Mean standardized uptake values (SUVmean) of renal graft cortex and aorta were measured in 4 and 1 volumes of interest, respectively. Spearman rank correlation coefficient (rho) and analysis of variance (ANOVA) were performed. RESULTS: Eighty-two KTRs underwent F-FDG PET/CT for tumor staging (n = 46), suspected infection (n = 11), or fever of unknown origin (n = 25). Mean eGFR was 50 +/- 19 mL/min per 1.73 m, including CKD stage 1 (n = 3), stage 2 (n = 21), stage 3a (n = 20), stage 3b (n = 29), and stage 4 (n = 9). Mean kidney and aorta SUVmean were 1.8 +/- 0.2 and 1.7 +/- 0.3, respectively. No significant correlation was observed between eGFR and kidney SUVmean (rho, 0.119; P, 0.28) or aorta SUVmean (rho, -0.144; P, 0.20). ANOVA showed no difference of kidney (P, 0.62) and aorta (P, 0.85) SUVmean between CKD groups. Mean coefficient of variation (on the basis of kidney SUVmean of >3 consecutive F-FDG PET/CT in 15 patients with no significant change of eGFR) reached 13.1%. CONCLUSIONS: The uptake of F-FDG by renal allografts within an hour postinjection is not significantly impacted by CKD. PMID- 27405042 TI - Effects of residual novaluron on reproduction in alfalfa leafcutting bees, Megachile rotundata F. (Megachilidae). AB - BACKGROUND: The chitin synthesis inhibitor novaluron can suppress pests that affect alfalfa seed production, but can negatively affect reproductive success in the alfalfa pollinator Megachile rotundata. Novaluron is considered to be a reduced-risk insecticide because it disrupts ecdysis and is non-lethal to adult insects, but some exposed adults have fewer eggs and suppressed egg hatch. For this experiment, bees nested in field cages where they were exposed to alfalfa that had never been treated with novaluron, alfalfa that had recently been sprayed or alfalfa that had been sprayed 1 and 2 weeks earlier. RESULTS: Compared with the control, greater proportions of dead eggs and larvae and lower proportions of live prepupae occurred when bees were exposed to recent novaluron sprays as well as one- or two-week old spray residues. Two possible routes of residual pesticide exposure were revealed. Mother bees become contaminated through ingestion or direct contact, or pollen-nectar provisions become contaminated with novaluron (1) on or within leaf pieces that surround provisions or (2) transferred from mother bees' bodies to provisions. CONCLUSION: We found strong immature mortality effects of novaluron and its residues on M. rotundata. Understanding all possible pesticide exposure routes for pollinating bees enhances decision-making for maintaining bee populations while protecting crops. (c) 2016 Society of Chemical Industry. PMID- 27405041 TI - Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy. AB - We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs. PMID- 27405044 TI - Catalytically Asymmetric Pd/Norbornene Catalysis: Enantioselective Synthesis of (+)-Rhazinal, (+)-Rhazinilam, and (+)-Kopsiyunnanine C1-3. AB - A catalytically asymmetric palladium/norbornene-catalyzed reaction is reported, where alpha-aryl tetrahydroquinoline derived phosphoramidite L15 is found to be the optimum ligand. Taking advantage of this transformation, the concise and unified enantioselective syntheses of (+)-rhazinal, (+)-rhazinilam, and (+) kopsiyunnanine C1, C2, and C3 are realized. PMID- 27405043 TI - Predictors of response to pegylated interferon in chronic hepatitis B: a real world hospital-based analysis. AB - Information on the efficacy of pegylated interferon (PEG-IFN) treatment of chronic hepatitis B (CHB) patients and predictors of the response based on real world data is limited. Consecutive 201 patients who underwent PEG-IFN treatment for CHB were reviewed. A virological response (VR) was defined as a serum HBV DNA of <2000 IU/mL, and a combined response (CR) was defined a VR accompanied by serological response for hepatitis B e antigen (HBeAg)-positive CHB. For HBeAg positive CHB patients, the HBeAg seroconversion rate and CR rate were 30.5% and 21.2% at 48 weeks after end of treatment (EOT), respectively. Baseline alanine aminotransferase (ALT) level was associated with HBeAg seroconversion, while baseline hepatitis B s antigen (HBsAg) levels of <250 IU/mL and HBV DNA <2.5 * 10(7) IU/mL were strongly associated with sustained off-treatment CR. For HBeAg negative CHB, the VR rates were 85.5%, and 27.7% at EOT, and 48 weeks after EOT, respectively; a baseline HBsAg <1,250 IU/mL was associated with sustained off treatment VR. PEG-IFN treatment has durable HBeAg seroconversion in HBeAg positive CHB, but results in a high risk of relapse among HBeAg-negative CHB patients. Pre-treatment HBsAg level is an important predictor of VR in CHB patients undergoing PEG-IFN treatment. PMID- 27405045 TI - Isolated Tubal Torsion With Endometriosis. PMID- 27405046 TI - Response to Letter to the Editor: Author's Reply. PMID- 27405047 TI - Precise Modulation of the Breathing Behavior and Pore Surface in Zr-MOFs by Reversible Post-Synthetic Variable-Spacer Installation to Fine-Tune the Expansion Magnitude and Sorption Properties. AB - To combine flexibility and modifiability towards a more controllable complexity of MOFs, a post-synthetic variable-spacer installation (PVSI) strategy is used to implement kinetic installation/ uninstallation of secondary ligands into/from a robust yet flexible proto-Zr-MOF. This PVSI process features precise positioning of spacers with different length, size, number, and functionality, enabling accurate fixation of successive breathing stages and fine-tuning of pore surface. It shows unprecedented synthetic tailorability to create complicated MOFs in a predictable way for property modification, for example, CO2 and R22 adsorption/separation, thermal/chemical stability, and extended breathing behavior. PMID- 27405049 TI - Evaluation of self-care skills training and solution-focused counselling for health professionals in psychiatric medicine: a pilot study. AB - OBJECTIVE: The purpose of this pilot study was to implement and to evaluate a self-care skills training with solution-focused counselling to support psychiatrists in handling their daily work challenges. METHODS: A total of 72 psychiatrists working in a psychiatric clinic were randomised in a single-blind trial to either an intervention group or a control group. Outcomes were measured at baseline and at the end of the training (follow-up 1: after 3 months; follow up 2: after 6 months). A validated questionnaire including the Perceived Stress Questionnaire, the Copenhagen Psychosocial Questionnaire, Brief Resilient Coping Scale, Self-Efficacy Scale and the Quality of Relationship Inventory was used. RESULTS: Psychiatrists in the intervention group reached a significant reduction in perceived job stress (p = 0.01, d = 0.05), improvements in job satisfaction (p = 0.02, d = 0.04), resilience (p = 0.02, d = 0.04) and self-efficacy (p = 0.04, d = 0.02) from baseline to all follow-ups with no comparable results seen in the control group. Psychiatrists stated an improved quality of physician-patient relationship (e.g. support, conflict management; p < 0.05). CONCLUSIONS: A self care skills training, including solution-focused counselling, for psychiatrists was associated with significant improvements in perceived stress, job satisfaction, individual protective skills and quality of relationship to patients. This training is suitable to implement as a group training program for psychiatrists. PMID- 27405048 TI - In Situ Spectral Kinetics of Cr(VI) Reduction by c-Type Cytochromes in A Suspension of Living Shewanella putrefaciens 200. AB - Although c-type cytochromes (c-Cyts) mediating metal reduction have been mainly investigated with in vitro purified proteins of dissimilatory metal reducing bacteria, the in vivo behavior of c-Cyts is still unclear given the difficulty in measuring the proteins of intact cells. Here, c-Cyts in living Shewanella putrefaciens 200 (SP200) was successfully quantified using diffuse-transmission UV/Vis spectroscopy due to the strong absorbance of hemes, and the in situ spectral kinetics of Cr(VI) reduction by c-Cyts were examined over time. The reduced product Cr(III) observed on the cell surface may play a role in inhibiting the Cr(VI) reduction and reducing the cell numbers with high concentrations (>200 MUM) of Cr(VI) evidenced by the 16S rRNA analysis. A brief kinetic model was established with two predominant reactions, redox transformation of c-Cyts and Cr(VI) reduction by reduced c-Cyts, but the fitting curves were not well-matched with c-Cyts data. The Cr(III)-induced inhibitory effect to the cellular function of redox transformation of c-Cyts was then added to the model, resulting in substantially improved the model fitting. This study provides a case of directly examining the reaction properties of outer-membrane enzyme during microbial metal reduction processes under physiological conditions. PMID- 27405050 TI - Mild Traumatic Brain Injury, PTSD, and Psychosocial Functioning Among Male and Female U.S. OEF/OIF Veterans. AB - This study examined the unique and combined relationship between mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) with psychosocial functioning in a cohort of 1,312 U.S. male and female veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) enrolled in the Veterans After Discharge Longitudinal Registry (Project VALOR). We assessed mTBI with structured screening questions reflective of current TBI classification standards and PTSD via the SCID-IV PTSD module; all other variables were assessed by self-report questionnaires. We identified significant diagnostic group differences in psychosocial functioning for both sexes. Individuals with PTSD, with or without a history of mTBI, reported significantly worse psychosocial functioning than individuals with mTBI alone or neither mTBI nor PTSD (males, eta(2) p = .11, p < .001; females, eta(2) p = .14, p < .001), even after adjusting for demographics and severity of chronic pain. The results suggested that veterans experiencing PTSD, regardless of whether they had a history of mTBI, were at increased risk for long-term psychosocial impairment. Further research examining possible benefits from improved access to resources and treatment to address these needs would be valuable. PMID- 27405052 TI - Early developmental milestones and age of independent walking in orphans compared with typical home-raised infants. AB - AIM: Early gross motor development is a major indicator of global milestones in the first year of life, affecting the walking ability of a child. There has been limited research reporting on early motor development and the age of independent walking of orphaned infants compared to typical home-raised infants. The purpose of this study was to compare the mean scores of early gross motor movement at 4, 6 and 8months of age and at the age of walking attainment of typically raised infants and orphaned infants. In addition, we looked to compare the walking age between these same infants. MATERIALS AND METHODS: This cross-sectional study recruited 59 typical home-raised infants and 62 orphans. Their gross motor development was assessed using the Alberta Infant Motor Scale (AIMS). The age of walking attainment was also prospectively monitored and ascertained. The Student's independent t-test was used to analyse the differences of the AIMS scores at 4, 6 and 8months of age and at the age of independent walking between the two groups. RESULTS: The orphans showed significantly lower AIMS scores at 4, 6 and 8months of age and the age of independent walking (P-value<0.05). The orphan group had a 5-month older mean age of walking attainment (15.0+/ 4.2months) compared with typical home-raised infants (9.9+/-1.4months). CONCLUSION: Orphans have delays in early gross motor development and walk independently at an older age, compared with home-raised infants. PMID- 27405053 TI - Risk of developmental delay: Comparison of late preterm and full term Canadian infants at age 12 months. AB - BACKGROUND: Late preterm (34(0/7) to 36(6/7)weeks gestation) infants may experience developmental delays greater than those found in term (>= 37(0/7)weeks gestation) infants. AIM: The aim of this study was to compare the risk of developmental delay between late preterm and full-term Canadian born infants at age 12months, and to determine infant and maternal factors associated with risk of delay. METHODS: A descriptive comparative study was conducted from data available from the All Our Babies community-based, prospective, pregnancy cohort in Calgary, Alberta. Participants were a sample of mothers of 52 infants born late preterm and 156 randomly selected mothers of term infants, matched for infant sex; eligible infants were singleton births. Mothers completed a developmental screening tool, the Ages and Stages Questionnaire, version 3 (ASQ 3), when their infant was age 12months. Corrected age (CA) was used for preterm infants. RESULTS: Both late preterm and term infants who required neonatal intensive care (NICU) were more likely to demonstrate risk of developmental delay. Compared to term infants, there was a trend for late preterm infants to be at risk of communication and gross motor delay at age 12months CA that was attenuated to the null when adjustments were made for NICU admission and other covariates. CONCLUSIONS: Infants born between 34 and 41weeks who are admitted to NICU are at increased risk of developmental delay. Early identification of risk provides an opportunity for referral for developmental assessment and early intervention programming. PMID- 27405054 TI - Impact of feeding method on diaphragm electrical activity and central apnea in preterm infants (FEAdi study). AB - BACKGROUND: In preterm infants, it is unknown whether feeding affects neural breathing pattern. OBJECTIVES: By measuring the diaphragm electrical activity (Edi) waveform, we evaluated the effect of enteral feeding and compared the effects of feeding methods on neural breathing pattern and central apnea in very low birth weight preterm infants. METHODS: In a prospective, randomized, crossover study, ten non-ventilated preterm infants with birth weights<1250g and tolerating full feeds were randomized to either bolus feeding (BF) or slow infusion feeding (SF) over 90min, followed by crossover to the other method at the next feed. Edi was continuously measured by a feeding catheter with miniaturized sensors. Five 15-min epochs were chosen [Baseline (BL), first 15min and 90min after BF/SF started] for breath-by-breath analyses of neural breathing pattern, including Edi peak, Edi min (end-expiratory), neural inspiratory and expiratory times, neural respiratory rate, and central apnea. Primary outcome was change in Edi min with feed. Secondary outcomes include change in Edi peak, frequency and duration of central apnea with feeding. RESULTS: Although intrasubject coefficient of variation was not significantly different, individual responses to feeding and feeding method were variable. No significant difference in Edi timing, Edi min, Edi peak, or apnea was observed for the different epochs. CONCLUSIONS: In this study cohort, neural breathing pattern does not appear to be consistently affected by enteral feeding or the feeding method. Compared with BF, SF does not appear to reduce the number or duration of apneas. PMID- 27405056 TI - Predictive role of early milestones-related psychomotor profiles and long-term neurodevelopmental pitfalls in preterm infants. AB - BACKGROUND: Developmental milestones are useful signposts developed to assess the pace and the trajectory of maturation occurring during specific time-windows called critical periods. The predictive role of their clinical assessment in premature infants is challenging, however, it actually represents an easy and reliable tool at follow-up. AIM AND STUDY DESIGN: Relying on a milestone-based neurological examination, we aimed to detect the interdependence between time of achievement of each milestone with long-term neuropsychological and neurodevelopmental outcomes. The influence of pre-perinatal events was also considered. PATIENTS & METHODS: Two-hundred-eighty patients (53.2% M) were serially assessed by classic neurological examination during the first 18months and subsequently evaluated by Griffiths Developmental Mental Scale. Children were sorted by ranges of gestational age and compared according to their different profiles. RESULTS: The Extremely PreTerms appeared to have a globally delayed development with subsequent attentional and behavioral troubles. Differently, the older peers, from Moderately to Full Term ones, although did not show significant differences in achievement of gross motor skills, had a stable delay of visual and social skills across the age ranges. This gap was not evidenced at the long term evaluation, except for the Extremely PreTerm children. Pre-perinatal factors played a significant role on short and long term neurodevelopmental outcome. CONCLUSIONS: Early assessed classic neurological examination might address neurodevelopmental trajectories in PreTerm children in which visual and social skills appear to be the mostly affected. It remains the easiest and most reliable tool of evaluation throughout the follow-up programs. PMID- 27405055 TI - Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. AB - BACKGROUND: In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac function or are caused by local morphological alterations in the ductus venosus. AIM: The aim of this study was to investigate if the observed increased nuchal translucency, cardiac defects and abnormal lymphatic development in the examined mouse models are associated with local changes in ductus venosus morphology. STUDY DESIGN: Mouse embryos with anomalous lymphatic development and nuchal edema (Ccbe1(-/-) embryos), mouse embryos with cardiac defects and nuchal edema (Fkbp12(-/-), Tbx1( /-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+) embryos) and mouse embryos with cardiac defects without nuchal edema (Tbx2(-/-), Fgf10(-/-), Jarid2(-/-NE-) embryos) were examined. Embryos were analyzed from embryonic day (E) 11.5 to 15.5 using markers for endothelium, smooth muscle actin, nerve tissue and elastic fibers. RESULTS: All mutant and wild-type mouse embryos showed similar, positive endothelial and smooth muscle cell expression in the ductus venosus at E11.5-15.5. Nerve marker and elastic fiber expression were not identified in the ductus venosus in all investigated mutant and wild-type embryos. Local morphology and expression of the used markers were similar in the ductus venosus in all examined mutant and wild type embryos. CONCLUSIONS: Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Ductus venosus flow velocity waveforms most probably reflect intracardiac pressure. PMID- 27405057 TI - The effects of aging on the working memory processes of multimodal information. AB - Normal aging is associated with deficits in working memory processes. However, the majority of research has focused on storage or inhibitory processes using unimodal paradigms, without addressing their relationships using different sensory modalities. Hence, we pursued two objectives. First, was to examine the effects of aging on storage and inhibitory processes. Second, was to evaluate aging effects on multisensory integration of visual and auditory stimuli. To this end, young and older participants performed a multimodal task for visual and auditory pairs of stimuli with increasing memory load at encoding and interference during retention. Our results showed an age-related increased vulnerability to interrupting and distracting interference reflecting inhibitory deficits related to the off-line reactivation and on-line suppression of relevant and irrelevant information, respectively. Storage capacity was impaired with increasing task demands in both age groups. Additionally, older adults showed a deficit in multisensory integration, with poorer performance for new visual compared to new auditory information. PMID- 27405058 TI - Electronic and magnetic properties of H-terminated graphene nanoribbons deposited on the topological insulator Sb2Te3. AB - Magnetism in zigzag graphene nanoribbons (GNRs) has received enormous attention recently, due to the one-dimensional nature of this phenomenon, as well as its potential applications in the field of spintronics. In this work, we present a density functional theory (DFT) investigation of H-passivated GNRs on the (111) surface of the topological insulator Sb2Te3. We show that the chemical interaction between the GNR and the substrate is weak. As a result, the GNR surface distance is large, of the order of 3.4 Angstrom, doping effects are almost negligible, and the mean-field magnetic properties of the GNR are preserved. Nevertheless, the presence of the substrate affects significantly the magnitude of the exchange coupling constants between the edges. Although our DFT calculations do not properly describe quantum fluctuations that destabilize the edge magnetism in free-standing GNRs, they provide important information about the stabilizing mechanisms which originate from the substrate-induced spin orbit coupling and the decoherence effects due to the surface states of Sb2Te3. We argue that, owing to these mechanisms, Sb2Te3 may be a suitable substrate to investigate experimentally the transition from "quantum" to "classical" magnetism in GNRs. PMID- 27405059 TI - Chlamydia psittaci infection increases mortality of avian influenza virus H9N2 by suppressing host immune response. AB - Avian influenza virus subtype H9N2 (H9N2) and Chlamydia psittaci (C. psittaci) are frequently isolated in chickens with respiratory disease. However, their roles in co-infection remain unclear. We tested the hypothesis that C. psittaci enhances H9N2 infection through suppression of host immunity. Thus, 10-day-old SPF chickens were inoculated intra-tracheally with a high or low virulence C. psittaci strain, and were simultaneously vaccinated against Newcastle disease virus (NDV). Significant decreases in body weight, NDV antibodies and immune organ indices occurred in birds with the virulent C. psittaci infection, while the ratio of CD4+/CD8+ T cells increased significantly compared to that of the lower virulence strain. A second group of birds were inoculated with C. psittaci and H9N2 simultaneously (C. psittaci+H9N2), C. psittaci 3 days prior to H9N2 (C. psittaci/H9N2), or 3 days after H9N2 (H9N2/C. psittaci), C. psittaci or H9N2 alone. Survival rates were 65%, 80% and 90% in the C. psittaci/H9N2, C. psittaci+H9N2 and H9N2/C. psittaci groups, respectively and respiratory clinical signs, lower expression of pro-inflammatory cytokines and higher pathogen loads were found in both C. psittaci/H9N2 and C. psittaci+H9N2 groups. Hence, virulent C. psittaci infection suppresses immune response by inhibiting humoral responses and altering Th1/Th2 balance, increasing mortality in H9N2 infected birds. PMID- 27405060 TI - Hepatic B cell leukemia-3 promotes hepatic steatosis and inflammation through insulin-sensitive metabolic transcription factors. AB - BACKGROUND & AIMS: The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-kappaB)-cofactor gene B cell leukemia-3 (Bcl-3) plays a critical role in altering the transcriptional capacity of NF-kappaB - a key inducer of inflammation - but also of genes involved in cellular energy metabolism. METHODS: To define the role of Bcl-3 in non-alcoholic steatohepatitis (NASH), we developed a novel transgenic mouse model with hepatocyte-specific overexpression of Bcl-3 (Bcl-3Hep) and employed a high-fat, high-carbohydrate dietary feeding model. To characterize the transgenic model, deep RNA sequencing was performed. The relevance of the findings was confirmed in human liver samples. RESULTS: Hepatocyte-specific overexpression of Bcl-3 led to pronounced metabolic derangement, characterized by enhanced hepatic steatosis from increased de novo lipogenesis and uptake, as well as decreased hydrolysis and export of fatty acids. Steatosis in Bcl-3Hep mice was accompanied by an augmented inflammatory milieu and liver cell injury. Moreover, Bcl-3 expression decreased insulin sensitivity and resulted in compensatory regulation of insulin-signaling pathways. Based on in vivo and in vitro studies we identified the transcription factors PPARalpha, PPARgamma and PGC-1alpha as critical regulators of hepatic metabolism and inflammation downstream of Bcl-3. Metformin treatment improved the metabolic and inflammatory phenotype in Bcl-3Hep mice through modulation of PPARalpha and PGC-1alpha. Remarkably, these findings were recapitulated in human NASH, which exhibited increased expression and nuclear localization of Bcl-3. CONCLUSIONS: In summary, Bcl-3 emerges as a novel regulator of hepatic steatosis, insulin sensitivity and inflammation in NASH. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is considered the most prevalent liver disease worldwide. Patients can develop end-stage liver disease resulting in liver cirrhosis or hepatocellular carcinoma, but also develop complications unrelated to liver disease, e.g., cardiovascular disease. Still there is no full understanding of the mechanisms that cause NAFLD. In this study, genetically engineered mice were employed to examine the role of a specific protein in the liver that is involved in inflammation and the metabolism, namely Bcl-3. By this approach, a better understanding of the mechanisms contributing to disease progression was established. This can help to develop novel therapeutic and diagnostic options for patients with NAFLD. PMID- 27405061 TI - Effects of Increasing Hydrocortisone to 300 mg Per Day in the Treatment of Septic Shock: a Pilot Study. AB - PURPOSE: The Surviving Sepsis Campaign guidelines recommend hydrocortisone in septic shock only when fluid resuscitation and vasopressors fail to restore hemodynamic stability. Hydrocortisone administration modalities are supported only by low-grade recommendations. Our main objective here was to determine differences in 28-day mortality between two low-dose hydrocortisone regimens for the treatment of septic shock. METHODS: We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every 6 h during 7 days (200-mg group; n = 59) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300-mg group; n = 63). Hydrocortisone was stopped abruptly at the end of treatment. RESULTS: There were no significant differences between the 200-mg and 300-mg groups as concerns 28-day mortality (respectively 52.5% vs. 44.4% [RR 0.84, 95% CI, 0.58-1.22, P = 0.47]), refractory shock incidence or delay from shock to vasopressor cessation. There were also no differences in adverse events between the groups. Shock relapse after hydrocortisone cessation was independent of hydrocortisone regimens, but it was associated with the persistence of infection and the use of etomidate. The resumption of hydrocortisone due to shock relapse was significantly more frequent in the 300-mg group. CONCLUSION: We found no differences in mortality or adverse events between the two hydrocortisone administration regimens. Shock relapse was significantly associated with the persistence of infection and the use of etomidate. PMID- 27405062 TI - Where's the Leak in Vascular Barriers? A Review. AB - Edema is typically presented as a secondary effect from injury, illness, disease, or medication, and its impact on patient wellness is nested within the underlying etiology. Therefore, it is often thought of more as an amplifier to current preexisting conditions. Edema, however, can be an independent risk factor for patient deterioration. Improper management of edema is costly not only to the patient, but also to treatment and care facilities, as mismanagement of edema results in increased lengths of hospital stay. Direct tissue trauma, disease, or inappropriate resuscitation and/or ventilation strategies result in edema formation through physical disruption and chemical messenger-based structural modifications of the microvascular barrier. Derangements in microvascular barrier function limit tissue oxygenation, nutrient flow, and cellular waste removal. Recent studies have sought to elucidate cellular signaling and structural alterations that result in vascular hyperpermeability in a variety of critical care conditions to include hemorrhage, burn trauma, and sepsis. These studies and many others have highlighted how multiple mechanisms alter paracellular and/or transcellular pathways promoting hyperpermeability. Roles for endothelial glycocalyx, extracellular matrix and basement membrane, vesiculo-vacuolar organelles, cellular junction and cytoskeletal proteins, and vascular pericytes have been described, demonstrating the complexity of microvascular barrier regulation. Understanding these basic mechanisms inside and out of microvessels aid in developing better treatment strategies to mitigate the harmful effects of excessive edema formation. PMID- 27405063 TI - Distinct Myocardial Mechanisms Underlie Cardiac Dysfunction in Endotoxemic Male and Female Mice. AB - In male mice, sepsis-induced cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca) handling, leading to depressed cellular Ca transients (DeltaCai). DeltaCai depression is partially due to inhibition of sarcoplasmic reticulum Ca ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie sepsis-induced cardiomyopathy in female mice is unknown.Male and female C57Bl/6J mice (WT), and mice deficient in the sGC alpha1 subunit activity (sGCalpha1), were challenged with lipopolysaccharide (LPS, ip). LPS induced mouse death and cardiomyopathy (manifested as the depression of left ventricular ejection fraction by echocardiography) to a similar degree in WT male, WT female, and sGCalpha1 male mice, but significantly less in sGCalpha1 female mice. We measured sarcomere shortening and DeltaCai in isolated, externally paced cardiomyocytes, at 37 degrees C. LPS depressed sarcomere shortening in both WT male and female mice. Consistent with previous findings, in male mice, LPS induced a decrease in DeltaCai (to 30 +/- 2% of baseline) and SERCA inhibition (manifested as the prolongation of the time constant of Ca decay, tauCa, to 150 +/- 5% of baseline). In contrast, in female mice, the depression of sarcomere shortening induced by LPS occurred in the absence of any change in DeltaCai, or SERCA activity. This suggested that, in female mice, the causative mechanism lies downstream of the Ca transients, such as a decrease in myofilament sensitivity for Ca. The depression of sarcomere shortening shortening after LPS was less severe in female sGCalpha1 mice than in WT female mice, indicating that cGMP partially mediates cardiomyocyte dysfunction.These results suggest, therefore, that LPS-induced cardiomyopathy develops through distinct sex specific myocardial mechanisms. While in males LPS induces sGC-independent decrease in DeltaCai, in female mice LPS acts downstream of DeltaCai, possibly via sGC-dependent myofilament dysfunction. PMID- 27405064 TI - Differential Expression of PCSK9 Modulates Infection, Inflammation, and Coagulation in a Murine Model of Sepsis. AB - INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) targets lipoprotein receptors for degradation, thereby reducing hepatic lipid clearance. PCSK9 inhibition reduces mortality in septic mice, presumably through increased hepatic clearance of pathogen lipids due to increased lipoprotein receptor concentrations. However, PCSK9 overexpression in vivo has not been studied in sepsis. Therefore, this study aimed to evaluate the effects of differential PCSK9 expression on systemic infection, inflammation, and coagulation in sepsis. METHODS: Wild-type, PCSK9 knockout (KO), and transgenic (Tg) mice that overexpress PCSK9 were subjected to sham surgery or cecal ligation and puncture (CLP). Bacterial loads were measured in lungs, peritoneal cavity fluid, and blood. Organ pathology was assessed in lungs, liver, and kidneys. Lung myeloperoxidase activity, and plasma concentrations of alanine aminotransferase (ALT), creatinine, cell-free DNA (cfDNA), protein C, thrombin-antithrombin (TAT) complexes, interleukin (IL)-6, and IL-10 were also measured 6 h postoperatively. Morbidity was assessed for 16 h following CLP. RESULTS: Overexpression of PCSK9 in mice increased liver and kidney pathology, plasma IL-6, ALT, and TAT concentrations during sepsis, whereas PCSK9 KO mice exhibited reduced bacterial loads, lung and liver pathology, myeloperoxidase activity, plasma IL-10, and cfDNA during CLP-induced sepsis. All septic mice had reduced plasma levels of protein C, but the protein C ratio relative to normal was significantly decreased in PCSK9 Tg mice. Dyspnea, cyanosis, and overall grimace scores were greatest in septic mice overexpressing PCSK9, whereas PCSK9 KO mice retained core body temperature during sepsis. CONCLUSION: These findings demonstrate that PCSK9 deficiency confers protection against systemic bacterial dissemination, organ pathology, and tissue inflammation, particularly in the lungs and liver, while PCSK9 overexpression exacerbates multi-organ pathology as well as the hypercoagulable and pro-inflammatory states in early sepsis. PMID- 27405065 TI - C1 Inhibitor Limits Organ Injury and Prolongs Survival in Swine Subjected to Battlefield Simulated Injury. AB - Complement system activation is recognized as a deleterious component of the mammalian physiological response to traumatic injury with severe hemorrhage (TH). Female Yorkshire swine were subjected to a simulated austere prehospital battlefield scenario. Each animal underwent controlled hemorrhage of 22 mL/kg at 100 mL/min rate for approximately 10 min followed by soft tissue injury, femur fracture, and spleen injury. Subsequent blood loss was uncontrolled. Twenty-eight minutes postinjury the animals were randomized into treatment or no treatment with recombinant human C1 esterase inhibitor (C1INH) (500 IU/kg, n = 11) and into receiving or not permissive hypotensive resuscitation (n = 14) with infusion of 45 mL/kg lactated Ringer's solution (2* blood lost). Observation and animal maintenance continued for 6 h at which time the animals had either expired or were euthanized. Heart, lung, and small intestine tissue samples were collected. Pharmacokinetic, hemodynamic, and metabolic parameters as well as survival time, plasma complement activity and tissue deposition, cytokine levels, and tissue injury were determined. We found that administration of C1INH protected tissues from damage, reduced the levels of inflammatory cytokines, and improved blood chemistry. Immunohistochemical analyses revealed that C1INH administration following TH markedly reduced complement activation and deposition in tissues. Importantly, C1INH administration prolonged survival of animals particularly in those which received resuscitation fluid infusion. Our data urge early administration of C1INH to limit organ damage and prolong survival of those injured in the battlefield. PMID- 27405066 TI - Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes. AB - OBJECTIVES: Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. METHODS/RESULTS: Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). CONCLUSIONS: Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment. PMID- 27405067 TI - Tactical Study of Care Originating in the Prehospital Environment (Tacscope): Acute Traumatic Coagulopathy on the Contemporary Battlefield. AB - BACKGROUND: Uncontrolled major hemorrhage and delayed evacuation remain substantial contributors to potentially survivable combat death, along with mission, environment, terrain, logistics, and hostile action. Life-saving interventions and the onset of acute traumatic coagulopathy (ATC) may also contribute. OBJECTIVE: Analyze US casualty records from the DoD Trauma Registry, using International Normalized Ratio (INR) of 1.5 for onset of ATC. METHODS: Retrospective cohort study from September 2007 to June 2011, inclusive. Independent variable was INR. Primary dependent variables were transfusion volume, massive transfusion (MT) defined as >10 units RBC/fresh whole blood in first 24 h, and 30-day survival. We used T test and chi-square analysis. Our IRB reviewed and exempted this study. RESULTS: In total, 8,913 cases were available. Fifty one percent had complete data with INR. Of excluded cases, 98.9% survived, average injury severity scales (ISS) was 7 (IQR 1-8), and less than 1% received MT. Among included cases, 98.5% survived, average ISS was 10 (IQR 2-14), average INR was 1.16 (CI95 1.14-1.17), and 2.7% received MT. There were 383 cases with ATC (8.4%). After stratification, we found that ATC cases were more likely to die (odds ratio (OR) 28, CI 16-48), receive MT (OR 9.6, CI 6.4-14.4), and were acidotic (pH 7.27 (7.24-7.31) vs. 7.38 (7.38-7.39)). Other significant differences included Injury Severity Score, Revised Trauma Score, blast mechanism, and penetrating injury. CONCLUSION: ATC is substantially associated with greater injury severity, MT, and mortality. Prehospital identification of MT casualties may expedite triage and evacuation, and enable remote damage control resuscitation to delay ATC onset and improve outcomes. PMID- 27405068 TI - Divergent Effects of Neutrophils on Fas-Induced Pulmonary Inflammation, Apoptosis, and Lung Damage. AB - Pulmonary Fas activation is essential in the pathogenesis of the acute respiratory distress syndrome. It remains unclear whether Fas-induced lung injury is dependent on neutrophils or mainly triggered by epithelial cell apoptosis. The contribution of lung epithelial cells (LEC) and alveolar macrophages (AM) remains elusive.Mice were neutrophil reduced prior to intratracheal instillation of Fas activating (Jo2) or isotype antibody for 6 or 18 h. LEC and AM were incubated with Jo2 and in the presence of nuclear factor kappa B, p-38 mitogen activated protein kinase (p38MAPK), or extracellular signal regulating kinase 1/2 (ERK1/2) inhibitors. Cytokines were assessed by cytometric bead array or ELISA. Apoptosis was quantified via active caspase-3 Western blotting and Terminal Deoxynucleotide Transferase dUTP Nick End Labeling (TUNEL). Lung injury was assessed by bronchoalveolar lavage fluid (BALF) protein concentration and lung histology.KC, IL-6, and MCP-1 were markedly increased in lung, plasma, and BALF 18 h after Jo2 in the presence of neutrophils; in neutrophil-reduced mice lungs, MCP-1, but not KC or IL-6, was even further enhanced. Six hours after Jo2, BALF protein was markedly increased only in the presence of neutrophils. Apoptosis remained unaffected by neutrophil reduction. AM released MCP-1 and underwent apoptosis at lower concentrations of Jo2 than LEC. Inhibition of p38MAPK significantly increased, while inhibition of ERK1/2 reduced AM and LEC apoptosis.In conclusion, neutrophils are a necessary component of Fas-induced lung damage, while not affecting lung apoptosis directly per se. LEC display higher resistance to Fas triggered inflammation and apoptosis than AM. PMID- 27405070 TI - Pharmacologic Considerations for Solid Organ Transplant Recipients Who Become Pregnant. AB - Females of childbearing age represent a large population of solid organ transplant recipients. With fertility commonly restored after transplantation, the possibility of pregnancy becomes a reality for many patients. Since the first published report of a successful pregnancy after solid organ transplantation in 1963, the number of pregnancies reported for female organ recipients has continued to increase. Despite this, information on the management of immunosuppression during pregnancy is limited, and a summary of these data is lacking in the literature. In addition to the many pharmacotherapeutic challenges in this unique patient population, physiologic changes in the peripartum period significantly affect the pharmacokinetics and pharmacodynamics of commonly used immunosuppressive agents. These changes, as well as the adverse effects and safety concerns of medications, must all be taken in to consideration to optimize outcomes for both mother and baby. In this review, we provide clinicians caring for female solid organ transplant recipients who wish to become pregnant or who are currently pregnant with a comprehensive review of maternal and fetal risks of pregnancy after transplantation. In addition, pharmacokinetic and pharmacodynamic changes of pregnancy will be discussed, and a summary of data regarding optimal immunosuppression management during pregnancy will be presented. PMID- 27405069 TI - ESI-MS studies of the non-covalent interactions between biologically important metal ions and N-sulfonylcytosine derivatives. AB - The aim of this report is to present the electrospray ionization mass spectrometry results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, 1-TsC, 1 and N-1 methanesulfonylcytosine, 1-MsC, 2 and their Cu(II) complexes Cu(1-TsC-N3)2 Cl2 , 3 and Cu(1-MsC-N3)2 Cl2 and 4 with biologically important cations: Na+ , K+ , Ca2+ , Mg2+ and Zn2+ . The formation of various complex metal ions was observed. The alkali metals Na+ and K+ formed clusters because of electrostatic interactions. Ca2+ and Mg2+ salts produced the tris ligand and mixed ligand complexes. The interaction of Zn2+ with 1-4 produced monometal and dimetal Zn2+ complexes as a result of the affinity of Zn2+ ions toward both O and N atoms. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27405071 TI - Facile one-step synthesis of nanocomposite based on carbon nanotubes and Nickel Aluminum layered double hydroxides with high cycling stability for supercapacitors. AB - Nickel-Aluminum Layered Double Hydroxide (NiAl-LDH) and nanocomposite of Carbon Nanotubes (CNTs) and NiAl-LDH (CNTs/NiAl-LDH) were prepared by using a facile one step homogeneous precipitation approach. The morphology, structure and electrochemical properties of the as-prepared CNTs/NiAl-LDH nanocomposite were then systematically studied. According to the galvanostatic charge-discharge curves, the CNTs/NiAl-LDH nanocomposite exhibited a high specific capacitance of 694Fg(-1) at the 1Ag(-1). Furthermore, the specific capacitance of the CNTs/NiAl LDH nanocomposite still retained 87% when the current density was increased from 1 to 10Ag(-1). These results indicated that the CNTs/NiAl-LDH nanocomposite displayed a higher specific capacitance and rate capability than pure NiAl-LDH. And the participation of CNTs in the NiAl-LDH composite improved the electrochemical properties. Additionally, the capacitance of the CNTs/NiAl-LDH nanocomposite kept at least 92% after 3000cycles at 20Ag(-1), suggesting that the nanocomposite exhibited excellent cycling durability. This strategy provided a facile and effective approach for the synthesis of nanocomposite based on CNTs and NiAl-LDH with enhanced supercapacitor behaviors, which can be potentially applied in energy storage conversion devices. PMID- 27405073 TI - Prevalence of pneumatized uncinate process and accompanying neighboring variations. AB - OBJECTIVES: This study aims to investigate the prevalence of uncinate process (UP) pneumatization and also to investigate the association of UP pneumatization with concurrent morphological variations in neighboring structures and the presence of maxillary sinusitis. PATIENTS AND METHODS: This was a retrospective study where coronal computed tomography scans of 1,500 UPs in 750 patients (483 males, 267 females; mean age 36.3+/-14.7 years; range 7 to 84 years) were examined to determine the prevalence of UP pneumatization and to assess any concurrent neighboring anatomical structures and the presence of maxillary sinusitis between January 2013 and June 2013. RESULTS: Uncinate process pneumatization was identified in a total of 6.26% of our patients with 1.60% being bilateral, 2.53% on the right only, and 2.13% on the left side only. Other than concurrent occurrences of right maxillary sinus septa (p=0.046), growth of the right ethmoidal bulla (p=0.044) and presence of maxillary sinusitis (right side: p=0.046, left side: p=0.035) were seen. CONCLUSION: We detected a 6.2% prevalence of UP pneumatization in our study group. An abnormally sized and over pneumatized UP can cause narrowing of the infundibulum and impaired sinus drainage. Such functional blockage can lead to recurrent maxillary sinusitis, stuffiness, and decreased olfaction. PMID- 27405072 TI - A 980nm driven photothermal ablation of virulent and antibiotic resistant Gram positive and Gram-negative bacteria strains using Prussian blue nanoparticles. AB - A 980nm laser-driven antimicrobial photothermal therapy using poly(vinylpyrrolidone) -coated Prussian Blue nanoparticles (PVP/PB NPs) is demonstrated. This approach allows an efficient eradication of a virulent strain of Gram-negative Escherichia coli (E. coli) associated with urinary tract infection as well as for the ablation of antibiotic resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA) and extended spectrum beta lactamase (ESBL) E. coli. Interestingly the 980nm irradiation exhibits minimal effect on mammalian cells up to a PVP/PB NPs concentration of 50MUgmL(-1), while at this concentration bacteria are completely eradicated. This feature is certainly very promising for the selective targeting of bacteria over mammalian cells. PMID- 27405074 TI - Endoscopic transcanal stapes surgery: our technique and outcomes. AB - OBJECTIVES: This study aims to evaluate the outcomes of endoscopic stapes surgery in terms of hearing gain and complications. PATIENTS AND METHODS: The medical records of 31 patients (13 males, 18 females; mean age 41.5+/-8.6 years; range 23 to 60 years) who underwent endoscopic stapes surgery in our clinic between April 2013 and June 2015 were retrospectively analyzed. The mean preoperative and postoperative pure tone bone conduction, air-bone gap, postoperative air-bone gap gain, duration of surgery and complications were evaluated. RESULTS: The right ear was operated on 15 patients and the left ear on 16 patients. The mean postoperative air-bone gap was statistically significantly improved, compared to preoperative values (p<0.001). The mean air-bone gap gain was 25.5+/-7.0 dB. CONCLUSION: Our study results suggest that endoscopy is a safe method which can be used in stapes surgery. PMID- 27405075 TI - The importance of voice analysis in evaluating the effectiveness of reflux treatment. AB - OBJECTIVES: This study aims to investigate the effects of reflux treatment in voice disorders in laryngopharyngeal reflux (LPR) patients using acoustic analyses and the relationship between scoring systems. PATIENTS AND METHODS: A total of 84 LPR patients (18 males, 66 females; mean age 43.1+/-11.3 years; range 18 to 73 years) were evaluated using reflux symptom index (RSI), reflux findings score (RFS), videolaryngostroboscopic examination, and acoustic analysis with Dr. Speech 4 before LPR treatment and at the first and third months after treatment. RESULTS: Maximum phonation time, fundamental frequency (F0), jitter, and shimmer scores did not show any statistically significant alteration at the posttreatment period according to pretreatment scores (p>0.05). However, the alteration in Harmonics-to-Noise ratio and Signals-to-Noise ratio scores were statistically significant (p=0.017 and p=0.003, respectively). Reflux symptom index results showed significant positive correlation with F0 at the pretreatment, and at posttreatment first and third month evaluations (Spearman's rank correlation coefficient [rho]=0.246, p=0.024; rho=0.300, p=0.006; rho=0.305, p=0.005, respectively). CONCLUSION: The relationship between the parameters of acoustic analysis and RSI and RFS values seems to be controversial for diagnosis and follow-up of LPR patients, requiring further investigations. PMID- 27405076 TI - Paratracheal lymph node dissection, in which patients should it be performed? AB - OBJECTIVES: This study aims to evaluate the effect of paratracheal lymph node (PTLN) metastasis on survival in patients with advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: Medical records of advanced laryngeal and hypopharyngeal cancers who underwent surgery between May 1995 and June 2008 were assessed and 78 of the patients (63 males, 15 females; mean age 55+/-11.3 years; range 25 to 76 years) who has PTLN metastasis were included in this study. The mean follow-up period was 23 months. Fifty-three patients had primary laryngeal cancer, and the remaining 25 patients had primary hypopharyngeal cancer. RESULTS: Paratracheal lymph node metastasis was detected in eight (15%) of 53 patients with laryngeal carcinoma, six (42%) of 14 patients with postcricoid carcinoma, and one (14%) of seven patients with posterior pharyngeal wall carcinoma. Paratracheal lymph node metastasis was not detected in patients with pyriform sinus carcinoma (n=4). Paratracheal lymph node metastasis was detected in a total of 15 patients, of whom 11 had extranodal spread (ENS). Multivariate analysis showed that the presence of ENS was the most effective prognostic factor on the overall survival (p<0.0005). CONCLUSION: The presence of PTLN metastasis with ENS is an important prognostic indicator on overall survival. We recommend PTLN dissection particularly in patients with advanced laryngeal or hypopharyngeal cancer for histopathological analysis and prognostication because ENS can only be precisely detected by pathological evaluation. PMID- 27405077 TI - Role of nasal problems on positional and nonpositional obstructive sleep apnea. AB - OBJECTIVES: This study aims to examine the relationship between nasal pathologies and positional (PP) obstructive sleep apnea (OSA) or nonpositional (NPP) OSA. PATIENTS AND METHODS: A total of 44 male OSA patients (mean age 48.0+/-6.8 years; range 31 to 60 years) suffering from nasal obstruction were retrospectively evaluated for nasal obstruction scores, overall apnea hypopnea index (AHI) and AHI in supine and nonsupine positions, daytime sleepiness scores, and body mass index (BMI). Patients were divided into two equal groups as PP group and NPP group. Output parameters were snoring severity index, clinical nasal obstruction score, septal deviation score, conchal hypertrophy score, and allergic rhinitis (AR) score. These parameters were correlated with the type of OSA. RESULTS: Apnea hypopnea index was significantly lower in PP group than in NPP group (p<0.03). Spearman correlation analysis revealed significant negative correlation between AR score and PP (r=-0.40, p<0.0001). Pearson correlation test revealed significant correlation between AHI and BMI (r=0.32, p<0.05). CONCLUSION: We suggest that AR is not only an important risk factor for OSA, but also patients with AR tend to be NPP OSA patients because of the serious nasal obstruction which already causes an increase in nasal resistance or pharyngeal collapsibility. PMID- 27405078 TI - Relationship between serum magnesium level and subjective tinnitus. AB - OBJECTIVES: This study aims to assess the relationship between serum magnesium level and bilateral subjective tinnitus. PATIENTS AND METHODS: The study included a total of 76 patients (36 males, 40 females; mean age 48.5+/-6.5 years; range 43 to 65 years) suffering from severe bilateral subjective tinnitus (accepted as severe and catastrophic according to tinnitus severity index) as the study group and 86 healthy participants (42 males, 44 females; mean age 43.8+/-7.3 years; range 40 to 61 years) as the control group. Serum magnesium levels of both groups were measured and compared statistically. RESULTS: The serum magnesium concentration was significantly lower in the study group compared to the control group (1.8+/-0.2 vs. 2.3+/-0.4 mg/dL, p=0.03). CONCLUSION: The significant association between serum magnesium level and tinnitus shows the importance of magnesium in the pathophysiology of subjective tinnitus. PMID- 27405079 TI - Vocal cord paralysis: What matters between idiopathic and non-idiopathic cases? AB - OBJECTIVES: This study aims to evaluate the demographic and clinical characteristics of patients with idiopathic and non-idiopathic vocal cord paralysis (VCP). PATIENTS AND METHODS: This retrospective cohort was performed on data extracted from medical files of 92 consecutive patients (43 males, 49 females; median age 52.1+/-23.1 years; min. 1 - max. 87) with VCP diagnosed in the otorhinolaryngology department between April 2012 and December 2015. Diagnoses associated with VCP, side of involvement (right, left or bilateral) and previous medical histories were noted and compared between patients with idiopathic and non-idiopathic VCP. RESULTS: Vocal cord paralysis occurred on the left side (n=56, 60.9%), right side (n=28, 30.4%) or bilaterally (n=8, 8.7%). A clinical entity related with VCP was identified in 63 patients (68.5%), while 29 (31.5%) patients had idiopathic VCP. Most common etiologies for VCP were thyroid surgery (n=32, 34.8%), cardiovascular surgery (n=9, 9.8%), lung cancer (n=6, 6.5%) and cardiac anomalies (n=4, 4.3%), respectively. Patients with idiopathic VCP were significantly older (p<0.001), while gender distribution (p=0.121) and side of involvement (p=0.340) did not differ between two groups. CONCLUSION: Vocal cord paralysis is a relatively common clinical entity with substantial rate of morbidity. Identification of the underlying etiology and awareness on the clinical characteristics are keystones for foreseeing complications and determining the appropriate therapeutic modality. PMID- 27405080 TI - [A case of brucellosis presenting with suppurative parotitis involvement]. AB - Brucellosis is a common zoonotic infection caused by Brucella bacteria. Brucella infections are usually presented with various clinical manifestations, and often accompanied by multiple organ involvements. In this article, we present a case of brucellosis with suppurative parotitis involvement accompanied by parotid abscess and fistula in a 60-year-old male patient. According to the literature review we conducted regarding complications of brucellosis, our case is the first case reported in the literature. Significant improvement in patient's suppurative parotitis and clinical findings was observed at the fifth week of combination antibiotic therapy. Patient's complaints resolved completely after eight weeks of treatment. PMID- 27405081 TI - Isolated middle ear meningioma. AB - Meningiomas are slowly progressive, benign tumors that originate from meningothelial cells. Extracranial meningiomas, especially isolated middle ear meningiomas, are very rare. In this article, we report a rare secretory type primary middle ear meningioma which was histopathologically confirmed in a 46 year-old female patient who presented with otological and neurootological symptoms. PMID- 27405083 TI - Co-occurrence of subacute granulomatous thyroiditis and papillary microcarcinoma. AB - Subacute thyroiditis, which is most commonly observed after a viral infection and may heal spontaneously, is an inflammatory thyroid disease. The co-occurrence of subacute thyroiditis and papillary carcinoma is quite rare. A 58-year-old male patient who applied to our hospital with the complaints of sore throat and neck swelling was performed total thyroidectomy following physical examination, ultrasound, and laboratory analysis. In histopathological examination, many granuloma structures were observed in both lobes, and a papillary microcarcinoma focus of 2 mm in diameter was seen in the left lobe. The co-occurrence of subacute thyroiditis and papillary carcinoma was deemed worthy of presentation as it is rarely observed. PMID- 27405082 TI - [Nasal type natural killer/T cell lymphoma: case series and literature review]. AB - Nasal type natural killer/T-cell lymphoma is a rare type of extranodal non Hodgkin lymphoma which originates from nasal cavity and paranasal sinuses. Exact diagnosis of nasal natural killer/T-cell lymphoma, which is a rapidly progressive clinical condition, may be established by immunohistochemical analysis on biopsy material after clinical suspicion. In this article, we report four cases of nasal natural killer/T-cell lymphoma who were followed-up in our clinic and discuss the diagnosis and treatment of the disease in light of the literature data. PMID- 27405084 TI - The effect of adenoid hypertrophy and adenoidectomy in patients on cardiovascular risk reduction. PMID- 27405086 TI - Hierarchically porous Fe-N-C derived from covalent-organic materials as a highly efficient electrocatalyst for oxygen reduction. AB - Developing high-performance non-precious catalysts to replace platinum as oxygen reduction reaction (ORR) catalysts is still a big scientific and technological challenge. Herein, we report a simple method for the synthesis of a FeNC catalyst with a 3D hierarchically micro/meso/macro porous network and high surface area through a simple carbonization method by taking the advantages of a high specific surface area and diverse pore dimensions in 3D porous covalent-organic material. The resulting FeNC-900 electrocatalyst with improved reactant/electrolyte transport and sufficient active site exposure, exhibits outstanding ORR activity with a half-wave potential of 0.878 V, ca. 40 mV more positive than Pt/C for ORR in alkaline solution, and a half-wave potential of 0.72 V, which is comparable to that of Pt/C in acidic solution. In particular, the resulting FeNC-900 exhibits a much higher stability and methanol tolerance than those of Pt/C, which makes it among the best non-precious catalysts ever reported for ORR. PMID- 27405085 TI - Impact of ABCB1 1236C > T-2677G > T-3435C > T polymorphisms on the anti proliferative activity of imatinib, nilotinib, dasatinib and ponatinib. AB - Overexpression of ABCB1 (also called P-glycoprotein) confers resistance to multiple anticancer drugs, including tyrosine kinase inhibitors (TKIs). Several ABCB1 single nucleotide polymorphisms affect the transporter activity. The most common ABCB1 variants are 1236C > T, 2677G > T, 3435C > T and have been associated with clinical response to imatinib in chronic myelogenous leukaemia (CML) in some studies. We evaluated the impact of these polymorphisms on the anti proliferative effect and the intracellular accumulation of TKIs (imatinib, nilotinib, dasatinib and ponatinib) in transfected HEK293 and K562 cells. ABCB1 overexpression increased the resistance of cells to doxorubicin, vinblastine and TKIs. Imatinib anti-proliferative effect and accumulation were decreased to a larger extent in cells expressing the ABCB1 wild-type protein compared with the 1236T-2677T-3435T variant relatively to control cells. By contrast, ABCB1 polymorphisms influenced the activity of nilotinib, dasatinib and ponatinib to a much lesser extent. In conclusion, our data suggest that wild-type ABCB1 exports imatinib more efficiently than the 1236T-2677T-3435T variant protein, providing a molecular basis for the reported association between ABCB1 polymorphisms and the response to imatinib in CML. Our results also point to a weaker impact of ABCB1 polymorphisms on the activity of nilotinib, dasatinib and ponatinib. PMID- 27405088 TI - Molecular Basis for the Recognition of Higher Fullerenes into Ureidopyrimidinone Cyclotriveratrylene Self-Assembled Capsules. AB - Fullerenes C60 , C70 , and C84 may be readily encaged within a hydrogen-bonded dimeric capsule, based on two concave cyclotriveratrylene (CTV) scaffolds, each containing three self-complementary 2-ureido-4-[1H]-pyrimidinone (UPy) subunits. NMR spectroscopy and circular dichroism studies, complemented by dispersion corrected DFT calculations, are reported with the aim of characterizing such capsule-fullerene complexes both structurally and energetically. Six fullerenes are considered: in agreement with experiments, calculations find that encapsulation is most favorable for C84 (on a par with C90 ), and follows the trend C60 2000 different proteins expressed in some cells under some conditions. The vast majority of these proteins are imported, in many cases by a dedicated protein import machinery. Recent proteomic studies have identified about 1000 different proteins in both Arabidopsis and potato mitochondria, but even for energy-related proteins, the most well-studied functional protein group in mitochondria, <75% of the proteins are recognized as mitochondrial by even one of six of the most widely used prediction algorithms. The mitochondrial proteomes contain proteins representing a wide range of different functions. Some protein groups, like energy-related proteins, membrane transporters, and de novo fatty acid synthesis, appear to be well covered by the proteome, while others like RNA metabolism appear to be poorly covered possibly because of low abundance. The proteomic studies have improved our understanding of basic mitochondrial functions, have led to the discovery of new mitochondrial metabolic pathways and are helping us towards appreciating the dynamic role of the mitochondria in the responses of the plant cell to biotic and abiotic stress. PMID- 27405098 TI - Intrusive Cognitive Content and Postdeployment Distress. AB - Although intrusive cognitions (ICs) are common posttrauma, little is known about trauma-related IC content, or associations between IC content and posttraumatic adjustment. A mixed-method cross-sectional approach was used in a secondary analysis of IC content and postdeployment distress. Participants were 1,521 U.S. Army soldiers 3-12 months postdeployment reporting their most distressing postdeployment ICs (mean number of ICs reported was 1.20). ICs were transcribed and content was categorized by 13 emergent themes. The most commonly reported ICs were of injury or death (48.2%) and combat (43.5%), and soldiers with probable posttraumatic stress disorder (PTSD; n = 187) were more likely to report the presence of these ICs, chi(2) s(1) = 35.27, ps < .001, phis < .16 than those without probable PTSD (n = 1,331). Other domains also emerged frequently, including ICs about friends (31.0%), family (15.8%), and leadership concerns (13.8%). IC content was a small, but significant correlate of distress after adjusting for combat exposure (DeltaR(2) >= .02, ps <= .001). The presence of ICs of injury or death, combat, military sexual trauma, health, leadership, and family (betas > .06, ps < .02) were unique correlates of distress. Results suggested that ICs about a wide range of topics should be addressed in postdeployment interventions. PMID- 27405096 TI - Stroke sensitivity in the aged: sex chromosome complement vs. gonadal hormones. AB - Stroke is a sexually dimorphic disease. Elderly women not only have higher stroke incidence than age-matched men, but also have poorer recovery and higher morbidity and mortality after stroke. In older, post-menopausal women, gonadal hormone levels are similar to that of men. This suggests that tissue damage and functional outcomes are influenced by biologic sex (XX vs. XY) rather than the hormonal milieu at older ages. We employed the Four Core Genotype (FCG) mouse model to study the contribution of sex chromosome complement and gonadal hormones to stroke sensitivity in aged mice in which the testis determining gene (Sry) is removed from the Y chromosome, allowing for the generation of XX males and XY females. XXF, XXM, XYF, XYM and XYwt aged mice were subjected to middle cerebral artery occlusion (MCAO). XXF and XXM mice had significantly larger infarct volumes than XYF and XYM cohorts respectively. There was no significant difference in hormone levels among aged FCG mice. XXF/XXM mice also had more robust microglial activation and higher serum levels of pro-inflammatory cytokines than XYF/XYM cohort respectively. We concluded that the sex chromosome complement contributes to ischemic sensitivity in aged animals and leads to sex differences in innate immune responses. PMID- 27405099 TI - Polybrominated Diphenyl Ethers in Human Milk and Serum from the U.S. EPA MAMA Study: Modeled Predictions of Infant Exposure and Considerations for Risk Assessment. AB - BACKGROUND: Serum concentrations of polybrominated diphenyl ethers (PBDEs) in U.S. women are believed to be among the world's highest; however, little information exists on the partitioning of PBDEs between serum and breast milk and how this may affect infant exposure. OBJECTIVES: Paired milk and serum samples were measured for PBDE concentrations in 34 women who participated in the U.S. EPA MAMA Study. Computational models for predicting milk PBDE concentrations from serum were evaluated. METHODS: Samples were analyzed using gas chromatography isotope-dilution high-resolution mass spectrometry. Observed milk PBDE concentrations were compared with model predictions, and models were applied to NHANES serum data to predict milk PBDE concentrations and infant intakes for the U.S. population. RESULTS: Serum and milk samples had detectable concentrations of most PBDEs. BDE-47 was found in the highest concentrations (median serum: 18.6; milk: 31.5 ng/g lipid) and BDE-28 had the highest milk:serum partitioning ratio (2.1 +/- 0.2). No evidence of depuration was found. Models demonstrated high reliability and, as of 2007-2008, predicted U.S. milk concentrations of BDE-47, BDE-99, and BDE-100 appear to be declining but BDE-153 may be rising. Predicted infant intakes (ng/kg/day) were below threshold reference doses (RfDs) for BDE-99 and BDE-153 but above the suggested RfD for BDE-47. CONCLUSIONS: Concentrations and partitioning ratios of PBDEs in milk and serum from women in the U.S. EPA MAMA Study are presented for the first time; modeled predictions of milk PBDE concentrations using serum concentrations appear to be a valid method for estimating PBDE exposure in U.S. infants. PMID- 27405100 TI - Fearing shades of grey: individual differences in fear responding towards generalisation stimuli. AB - Individual differences in fear generalisation have been proposed to play a role in the aetiology and/or maintenance of anxiety disorders, but few data are available to directly support that claim. The research that is available has focused mostly on generalisation of peripheral and central physiological fear responses. Far less is known about the generalisation of avoidance, the behavioural component of fear. In two experiments, we evaluated how neuroticism, a known vulnerability factor for anxiety, modulates an array of fear responses, including avoidance tendencies, towards generalisation stimuli (GS). Participants underwent differential fear conditioning, in which one conditioned stimulus (CS+) was repeatedly paired with an aversive outcome (shock; unconditioned stimulus, US), whereas another was not (CS-). Fear generalisation was observed across measures in Experiment 1 (US expectancy and evaluative ratings) and Experiment 2 (US expectancy, evaluative ratings, skin conductance, startle responses, safety behaviours), with overall highest responding to the CS+, lowest to the CS- and intermediate responding to the GSs. Neuroticism had very little impact on fear generalisation (but did affect GS recognition rates in Experiment 1), in line with the idea that fear generalisation is largely an adaptive process. PMID- 27405101 TI - Meat eaters by dissociation: How we present, prepare and talk about meat increases willingness to eat meat by reducing empathy and disgust. AB - Many people enjoy eating meat but dislike causing pain to animals. Dissociating meat from its animal origins may be a powerful way to avoid cognitive dissonance resulting from this 'meat paradox'. Here, we provide the first comprehensive test of this hypothesis, highlighting underlying psychological mechanisms. Processed meat made participants less empathetic towards the slaughtered animal than unprocessed meat (Study 1). When beheaded, a whole roasted pork evoked less empathy (Study 2a) and disgust (Study 2b) than when the head was present. These affective responses, in turn, made participants more willing to eat the roast and less willing to consider an alternative vegetarian dish. Conversely, presenting a living animal in a meat advertisement increased empathy and reduced willingness to eat meat (Study 3). Next, describing industrial meat production as "harvesting" versus "killing" or "slaughtering" indirectly reduced empathy (Study 4). Last, replacing "beef/pork" with "cow/pig" in a restaurant menu increased empathy and disgust, which both equally reduced willingness to eat meat and increased willingness to choose an alternative vegetarian dish (Study 5). In all experiments, effects were strongly mediated by dissociation and interacted with participants' general dissociation tendencies in Study 3 and 5, so that effects were particularly pronounced among participants who generally spend efforts disassociating meat from animals in their daily lives. Together, this line of research demonstrates the large role various culturally-entrenched processes of dissociation play for meat consumption. PMID- 27405102 TI - Stereoselective beta-Mannosylation by Neighboring-Group Participation. AB - The stereoselective synthesis of glycosidic bonds is the main challenge of oligosaccharide synthesis. Neighboring-group participation (NGP) of C2 acyl substituents can be used to provide 1,2-trans-glycosides. Recently, the application of NGP has been extended to the preparation of 1,2-cis-glycosides with the advent of C2 chiral auxiliaries. However, this methodology has been strictly limited to the synthesis of 1,2-cis-gluco-type sugars. Reported herein is the design and synthesis of novel mannosyl donors which provide 1,2-cis mannosides by NGP of thioether auxiliaries. A key element in the design is the use of (1) C4 locked mannuronic acid lactones to enable NGP of the C2 auxiliary. In addition to C2 participation a new mode of remote participation of the C4 benzyl group was identified and provides 1,2-cis-mannosides. PMID- 27405103 TI - A Comprehensive study of the Effects of Chain Morphology on the Transport Properties of Amorphous Polymer Films. AB - Organic semiconductors constitute one of the main components underlying present day paradigm shifting optoelectronic applications. Among them, polymer based semiconductors are deemed particularly favorable due to their natural compatibility with low-cost device fabrication techniques. In light of recent advances in the syntheses of these classes of materials, yielding systems exhibiting charge mobilities comparable with those found in organic crystals, a comprehensive study of their charge transport properties is presented. Among a plethora of effects arising from these systems morphological and non morphological attributes, it is shown that a favorable presence of several of these attributes, including that of rapid on-chain carrier propagation and the presence of elongated conjugation segments, can lead to an enhancement of the system's mobility by more than 5 orders of magnitude with respect to 'standard' amorphous organic semiconductors. New insight for the formulation of new engineering strategies for next generation polymer based semiconductors is thus gathered. PMID- 27405104 TI - Phenylpyruvic Acid-2-O-beta-D-Glucoside Attenuates High Glucose-Induced Apoptosis in H9c2 Cardiomyocytes. AB - Chronic hyperglycemia is closely associated with impaired substrate metabolism, dysregulated mitochondrial membrane potential, and apoptosis in the diabetic heart. As adult cardiomyocytes display a limited capacity to regenerate following an insult, it is essential to protect the myocardium against the detrimental effects of chronic hyperglycemia. This study therefore investigated whether phenylpyruvic acid-2-O-beta-D-glucoside, present in Aspalathus linearis (rooibos), is able to attenuate hyperglycemia-induced damage in H9c2 cardiomyocytes. H9c2 cardiomyocytes were exposed to a high glucose concentration (33 mM) prior to treatment with phenylpyruvic acid-2-O-beta-D-glucoside (1 uM), metformin (1 uM), or a combination of phenylpyruvic acid-2-O-beta-D-glucoside and metformin (both at 1 uM). Our data revealed that high glucose exposure increased cardiac free fatty acid uptake and oxidation, mitochondrial membrane potential, and apoptosis (caspase 3/7 activity and TUNEL), and decreased the Bcl2/Bax protein expression ratio. Phenylpyruvic acid-2-O-beta-D-glucoside treatment, alone or in combination with metformin, attenuated these glucose-induced perturbations, confirming its protective effect in H9c2 cardiomyocytes exposed to chronic hyperglycemia. PMID- 27405105 TI - New Sulphated Flavonoids from Tamarix africana and Biological Activities of Its Polar Extract. AB - The phytochemical investigation of Tamarix africana Poir. (Tamaricaceae) shoot polar extract afforded three new sulphated flavonoids, (2S,4R)-5,7,4' trihydroxyflavan-4-ol 5,7-disulphate (1), (2S)-5,7,4'-trihydroxyflavan 7-O sulphate (2), and (2S)-naringenin 4'-O-sulphate (3), together with ten known compounds. Their structures were determined by spectroscopic methods including 1D and 2D NMR analysis and HRMS. Biological activities of the polar extract of T. africana shoots related to its phenolic content were also investigated. A high total phenolic content (151.1 mg GAE/g) was found in the methanol shoot extract, which exhibits strong antioxidant activities using the oxygen radical absorbance capacity method and a skin cell-based assay. Moreover, the shoot extract showed significant anti-inflammatory activity, reducing nitric oxide release by 53.5 % at 160 ug/mL in lipopolysaccharide-stimulated RAW 264.7 macrophages. Finally, T. africana shoot extract inhibited the growth of A-549 lung carcinoma cells, with an IC50 value of 34 ug/mL. PMID- 27405106 TI - Antifungal Amide Alkaloids from the Aerial Parts of Piper flaviflorum and Piper sarmentosum. AB - Sixty-three amide alkaloids, including three new, piperflaviflorine A (1), piperflaviflorine B (2), and sarmentamide D (4), and two previously synthesized ones, (1E,3S)-1-cinnamoyl-3- hydroxypyrrolidine (3) and N-[7'-(4' methoxyphenyl)ethyl]-2-methoxybenzamide (5), were isolated from the aerial parts of Piper flaviflorum and Piper sarmentosum. Their structures were elucidated by detailed spectroscopic analysis and, in case of 3, by single-crystal X-ray diffraction. Most of the isolates were tested for their antifungal and antibacterial activities. Ten amides (6-15) showed antifungal activity against Cryptococcus neoformans ATCC 90 113 with IC50 values in the range between 4.7 and 20.0 ug/mL. PMID- 27405107 TI - Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-RSV Activities. AB - Five new diterpenoid alkaloids, ajacisines A-E (1-5), were isolated from Delphinium ajacis, along with seven known alkaloids (6-12). On the basis of their spectral data (IR, UV, HR-ESI-MS, 1D and 2D NMR) and chemical properties, the structures of compounds 1-12 were identified. All isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with IC50 values of 75.2 +/- 1.1, 35.1 +/- 0.6, 10.1 +/- 0.3, and 50.2 +/- 0.5 uM, respectively. PMID- 27405108 TI - Guaiane-Type Sesquiterpenoids from Fissistigma oldhamii Inhibit the Proliferation of Synoviocytes. AB - Three guaiane-type sesquiterpenoids, dysodensiols G-I (1-3), together with five known sesquiterpenoids (4-8) were isolated from the stems of Fissistigma oldhamii (Hemsl.) Merr. Compound 1 represents the first example of an ene(6 -> 5)-abeo-14 norguaiane sesquiterpenoid derived from natural products. Their structures were elucidated by a combination of 1D and 2D NMR and MS spectra. The absolute configuration of 2 was determined by an X-ray crystallographic analysis. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed a potent inhibitory effect on the proliferation of synoviocytes with an IC50 value of 1.0 uM. PMID- 27405109 TI - Ionic Liquids Can Permanently Modify Porous Silicon Surface Chemistry. AB - To develop ionic liquid/porous silicon (IL/pSi) microarrays we have contact pin printed 20 hydrophobic and hydrophilic ionic liquids onto as-prepared, hydrogen passivated porous silicon (ap-pSi) and then determined the individual IL spot size, shape and associated pSi surface chemistry. The results reveal that the hydrophobic ionic liquids oxidize the ap-pSi slightly. In contrast, the hydrophilic ionic liquids lead to heavily oxidized pSi (i.e., ox-pSi). The strong oxidation arises from residual water within the hydrophilic ILs that is delivered from these ILs into the ap-pSi matrix causing oxidation. This phenomenon is less of an issue in the hydrophobic ILs because their water solubility is substantially lower. PMID- 27405110 TI - An Overview on Predictive Biomarkers of Testicular Germ Cell Tumors. AB - Testicular germ cell tumors (TGCTs) are frequent solid malignant tumors and cause of death in men between 20-40 years of age. Genetic and environmental factors play an important role in the origin and development of TGCTs. Although the majority of TGCTs are responsive to chemotherapy, about 20% of patient presents incomplete response or tumors relapse. In addition, the current treatments cause acute toxicity and several chronic collateral effects, including sterility. The present mini-review collectively summarize the most recent findings on the new discovered molecular biomarkers such as tyrosine kinases, HMGAs, Aurora B kinase, and GPR30 receptor predictive of TGCTs and as emerging new possible molecular targets for therapeutic strategies. J. Cell. Physiol. 232: 276-280, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27405112 TI - Authors' Response. PMID- 27405113 TI - [Ginko-extract added to S3 guideline]. PMID- 27405111 TI - miR-638 suppresses DNA damage repair by targeting SMC1A expression in terminally differentiated cells. AB - The reduction of DNA damage repair capacity in terminally differentiated cells may be involved in sensitivity to cancer chemotherapy drugs; however, the underlying molecular mechanism is still not fully understood. Herein, we evaluated the role of miR-638 in the regulation of DNA damage repair in terminally differentiated cells. Our results show that miR-638 expression was up regulated during cellular terminal differentiation and involved in mediating DNA damage repair processes. Results from a luciferase reporting experiment show that structural maintenance of chromosomes (SMC)1A was a potential target of miR-638; this was verified by western blot assays during cell differentiation and DNA damage induction. Overexpression of miR-638 enhanced the sensitivity of cancer cells to cisplatin, thus reducing cell viability in response to chemotherapy drug treatment. Furthermore, miR-638 overexpression affected DNA damage repair processes by interfering with the recruitment of the DNA damage repair-related protein, gammaH2AX, to DNA break sites. These findings indicate that miR-638 might act as a sensitizer in cancer chemotherapy and accompany chemotherapy drugs to enhance chemotherapeutic efficacy and to improve the chance of recovery from cancer. PMID- 27405114 TI - Sleep Distubances in Individuals with Dementia. PMID- 27405115 TI - Treating Acute Coronary Syndrome. PMID- 27405116 TI - Author's Response. PMID- 27405117 TI - LONGITUDINAL EVALUATION OF MALARIA EPIDEMIOLOGY IN AN ISOLATED VILLAGE IN WESTERN THAILAND: I. STUDY SITE AND ADULT ANOPHELINE BIONOMICS. AB - This is the first in a series of papers describing the epidemiology of malaria in an isolated village in western Thailand. The study site was the village of Kong Mong Tha, located in Sangkhla Buri District, Kanchanaburi Province, Thailand. In this paper we present an overview of the study site and results from our adult anopheline mosquito surveillance conducted over 56 consecutive months from June 1999 until January 2004. The collection site, indoor/outdoor location, parity, biting activity and Plasmodiumfalciparum (Pf) and P. vivax (Pv) infection rates were used to calculate seasonal entomological inoculation rates for the predominant four Anopheles species. A total of 21,566 anophelines representing 28 distinct species and 2 groups that were not identified to species were collected using human bait, with almost 95% of the collection consisting of Anopheles minimus, An. maculatus, An. sawadwongporni and An. barbirostris/campestris. Mosquitoes generally peaked during the wet season, were collected throughout the night, and were collected most often outside (ca. 75%) versus inside (ca. 25%) of houses. Approximately 50% of collected mosquitoes were parous. Overall Plasmodium infection rates were 0.27%, with a total of 16 and 42 pools of Pf- and Pv positive mosquitoes, respectively. Annual EIRs were 2.3 times higher for Pv than for Pf, resulting in approximately 5.5 and 2.6 infective bites per person per year, respectively. The results suggest An. minimus and An. maculatus are the primary and secondary vectors of Pf and Pv transmission in Kong Mong Tha, while An. sawadwongporni and An. barbirostris/campestris also appear to play a role based on the presence of circumsporozoite protein (CSP) in the head/thorax of the specimens tested. PMID- 27405118 TI - PFMDR1 POLYMORPHISMS INFLUENCE ON IN VITRO SENSITIVITY OF THAI PLASMODIUM FALCIPARUM ISOLATES TO PRIMAQUINE, SITAMAQUINE AND TAFENOQUINE. AB - Primaquine (PQ), an 8-aminoquinoline, is considered a tissue schizonticide drug for radical cure in vivax and ovale malaria, with minimal impact on asexual erythrocytic stages at therapeutic concentrations. Tafenoquine (TQ), a new 8 aminoquinoline analog of PQ, is active against both malaria parasite tissue and blood stages and is being promoted as a drug candidate for antimalarial chemotherapy and chemoprophylaxis and potential transmission blocking against Plasmodium vivax and P. falciparum. This study compared in vitro sensitivity of Thai P. falciparum isolates against three 8-aminoquinolines, PQ, TQ and sitamaquine (SQ), a related 8-aminoquinoline and assessed the importance of pfmdr1 polymorphism on the in vitro response. Seventy-eight laboratory adapted Thai P. falciparum isolates were evaluated for in vitro sensitivity to the three 8-aminoquinolines using a radioisotopic assay, and pfmdr1 polymorphisms were determined using PCR-based methods. All three drugs have weak antiplasmodial activity against asexual erythrocytic stage with SQ being the most potent by almost 10 folds. Cross susceptibility was observed in all three 8 aminoquinolines. Parasites containing pfmdr1 86Y, 184Y or 1034S allele exhibit significantly higher PQ IC50. TQ sensitivity was reduced in those parasites containing pfmdr1 86Y, 1034S or 1042N allele. However, there was no significant influence of pfmdr1 alleles on SQ sensitivity. The data highlight unique differences among three representative 8-aminoquinoline drugs that may be useful in understanding their potential utility in antimalarial development. PMID- 27405119 TI - PHYLOGENY OF ANGIOSTRONGYLUS CANTONENSIS IN THAILAND BASED ON CYTOCHROME C OXIDASE SUBUNIT I GENE SEQUENCE. AB - Angiostrongylus cantonensis is an emerging infectious agent causing eosinophilic meningitis or meningoencephalitis in humans with clinical manifestation of severe headache. Molecular genetic studies on classification and phylogeny of A. cantonensis in Thailand are limited. This study surveyed A. cantonensis larvae prevalence in natural intermediate hosts across Thailand and analyzed their phylogenetic relationships. A total of 14,032 freshwater and land snails were collected from 19 provinces of Thailand. None of Filopaludina sp, Pomacea sp, and Cyclophorus sp were infected with Angiostrongylus larvae, whereas Achatina fulica, Cryptozona siamensis, and Megaustenia siamensis collected from Kalasin, Kamphaeng Phet, Phetchabun, Phitsanulok, and Tak Provinces were infected, with C. siamensis being the common intermediate host. Based on morphology, larvae isolated from 11 samples of these naturally infected snails preliminarily were identified as A. cantonensis. Comparison of partial nucleotide sequences of cytochrome c oxidase subunit I gene revealed that four sequences are identical to A. cantonensis haplotype ac4 from Bangkok and the other seven to that of A. cantonensis isolate AC Thai, indicating two independent lineages of A. cantonensis in Thailand. PMID- 27405120 TI - MITOCHONDRIAL GENE SEQUENCES AMONG DIFFERENT GEOGRAPHICAL ISOLATES OF SCHISTOSOMA JAPONICUM IN YUNNAN PROVINCE, CHINA. AB - In order to evaluate differentiate genetic differences among Schistosoma japonicum isolates from Dali Ancient City, Xizhou and Yongsheng County, Yunnan Province, China, mitochondrial col, cytb, nd1, nd6, and nd4l were PCR amplified and sequenced, revealing nucleotide difference(s) among these strains of 8, 1, 5, 4, and 0, respectively. Phylogenetic analysis showed that S. japonicum from the three different geographical locations of Yunnan Province were clustered genetically together and were more similar to S. malayensis and S. mekongi than S. haematobium or S. mansoni. For intra-species differentiation purposes, Schistosoma mitochondrial col, nd1, and nd6 are better genetic markers than cytb and nd41. PMID- 27405121 TI - TAENIA SAGINATA INFECTION IN A 14-MONTH-OLD TODDLER. AB - A 14-month-old female toddler presented with a 3-day history of pass- ing gravid proglottids of Taenia saginata. Neither she nor her family members had a history of eating raw beef or other raw meat. Single doses of praziquantel and niclosamide were administered. To the best of our knowledge, this is the youngest described patient with T. saginata infection to date. PMID- 27405122 TI - PREVALENCE OF TREMATODE LARVAE IN INTERMEDIATE HOSTS: SNAILS AND FISH IN KO AE SUB-DISTRICT OF KHUEANG NAI, UBON RATCHATHANI PROVINCE, THAILAND. AB - Ko Ae Sub-district of Khueang Nai, Ubon Ratchathani Province, Thailand is located in an endemic area for Opisthorchis viverrini and other fish-borne zoonotic trematodes (FZT) infection. This study shows the status in Ko Ae Sub-district of FZT infection based on availability of intermediate hosts and necessary requirements for the transmission of FZT. A cross-sectional survey of intermediate hosts of FZT, including Bithynia siamensis goniomphalos and cyprinoid fish, was conducted from April 2013 to December 2014. Examination of 1,000 snails revealed 3.4% were infected with trematode cercariae, with a density of infection greater than 100 cercariae per infected snail. Six groups of morphologically-distinguishable trematode cercariae were identified, namely, cystophorous, echinostome, furcocercous, mutabile, parapleurolophocercous, and xiphidio, the latter being the most predominant type. Among 250 cyprinoid fish samples with metacercariae present at their caudal fins and examined for FZT by pepsin digestion, metacer- cariae of Haplorchis taichui, H. pumilio, and Centrocestus formosanus were found. Unidentified metacercariae collected from fish caudal fins were subsequently shown using a PCR-based assay to be C. formosanus. No infection by O. viverrini in the intermediate hosts, Bithynia siamensis goniomphalos and cyprinoid fish was evident. The study provides new information regarding trematode larvae infection in the primary and secondary intermediate hosts of FZT in this area of Thailand. PMID- 27405123 TI - EFFICACY OF THAI NEEM OIL AGAINST AEDES AEGYPTI (L.) LARVAE. AB - Trees with larvicidal activity may be found in Thailand. We conducted this study to evaluate the efficacy and length of efficacy of Thai neem (Azadirachta siamensis) oil emulsion and an alginate bead of Thai neem oil formulation against early fourth stage Aedes aegypti larvae using a dipping test. The Thai neem oil emulsion had significantly greater larvicidal activity than the alginate bead formulation at 12 to 60 hours post-exposure (p < 0.01). The Thai neem oil formulation resulted in 100% mortality among the early fourth stage Aedes aegypti larvae at 48 hours, while the alginate bead formulation resulted in 98% larval mortality at 84 hours and 100% mortality at 96 hours. The mean larval mortality using the Thai neem oil emulsion dropped to < 25% by 12 days and with the alginate beads dropped to < 25% by 15 days of exposure. PMID- 27405124 TI - FIRST DETECTION OF CHICKEN ANEMIA VIRUS AND NOROVIRUS GENOGROUP II IN STOOL OF CHILDREN WITH ACUTE GASTROENTERITIS IN TAIWAN. AB - To date, there has been no report of co-infection of chicken anemia virus (CAV) with enteric virus in patients with acute gastroenteritis (AGE). CAV has been recently detected in various types of human samples including stool, indicating pathogenicity in gastrointestinal tract. Examination by PCR-based methods of CAV and norovivus genogroup II (NV GII) in stool of 110 children with AGE at a hospital in Taiwan revealed for the first time of co-infection in two cases. This is the first description of CAV infection in children with AGE in Taiwan. Systematic surveillance and evidence-based studies are required to determine the transmission pathways and spread of CAV in Taiwan. PMID- 27405125 TI - KNOWLEDGE OF MEDICAL FACULTY STUDENTS CONCERNING EBOLA IN MALATYA, TURKEY. AB - The purpose of this study was to determine the knowledge levels of Inonu University medical faculty students regarding Ebola. This descriptive, cross sectional study was conducted between November and December, 2014 at Inonu University Medical Faculty. After the researchers performed the literature review, a questionnaire comprising 39 questions was prepared, and the students were asked to fill them out. Nine hundred and eighty-four of 1,298 students (75.8%) participated in the study. Seventy-three point seven percent knew that the Ebola virus disease had high fatality rate, 51.9% of them knew that the primary method of infection was contact with the secretions of dead animals and humans, and 55.2% knew that it was transmitted via the blood of infected animals. The rate of knowing that there was no specific vaccination was 62.1%, while the knowledge that there was no specific treatment was 45.3%; 80.4% knew that all the people entering the patient's room had to wear gloves and liquid-resistant aprons, and 77.3% knew that the number of the staff caring for the patient must be reduced to the minimum level. Three knowledge points were calculated in the study: 'Knowledge Points on Ebola Virus Disease Factor Properties and the Methods of Infection,' 'Ebola Virus Disease Symptom Knowledge Points,' and 'Ebola Virus Disease Protection Knowledge Points.' In terms of these knowledge points, the knowledge levels of the students between the classes were significantly different. PMID- 27405126 TI - LEPTOSPIROSIS INCIDENCE AND MORTALITY IN MALAYSIA. AB - Leptospirosis is endemic in Southeast Asia, Central and South America, the Caribbean, and Oceania. Malaysia was categorized as a probable endemic country without any available data. Thus, this study was conducted to determine incidence, case fatality rate and mortality rate of leptospirosis. Leptospirosis is a notifiable disease in Malaysia since 2010 whereby probable or confirmed cases must be notified to relevant health district office. There were 3,665 and 4,457 probable and laboratory confirmed leptospirosis cases notified in 2012 and 2013, respectively. In the 2-year period, the most common age group of patients was 19 years old or less (23.3%) with male:female ratio of 2.61:1. Students consisted about 16.9% of patients, followed by agriculture-based or plantation workers (14.7%). Overall age-standardized incidence rate of leptospirosis in Malaysia for 2012 and 2013 was 29.02 per 100,000. Overall case fatality rate was 1.47% for 2-year period and overall age-standardized mortality rate was 0.45 per 100,000. Leptospirosis is an emerging public health concern in Malaysia and may pose a significant health impact and burden to the nation in the coming years if not well controlled. PMID- 27405127 TI - PREVALENCE AND RISK FACTORS FOR ASYMPTOMATIC INTESTINAL MICROSPORIDIOSIS AMONG ABORIGINAL SCHOOL CHILDREN IN PAHANG, MALAYSIA. AB - The epidemiology and environmental factors affecting transmission of human microsporidiosis are poorly understood. We conducted the present study to determine the prevalence and risk factors associated with asymptomatic intestinal microsporidiosis among aboriginal school children in the Kuala Krau District, Pahang State, Malaysia. We collected stool samples from 255 school children and examined the samples using Gram-chromotrope Kinyoun stain. We also collected demographic, socioeconomic, environmental and personal hygiene information using a pre-tested questionnaire. Sixty-nine of the children was positive for microsporidia: 72.5% and 27.5% were low (1+) and moderate (2+) excretions of microsporidia spores, respectively. Univariate and multivariate analyses showed being aged 10 years (p = 0.026), using an unsafe water supply as a source for drinking water (p = 0.044) and having close contact with domestic animals (p = 0.031) were all significantly associated with microsporidial infection among study subjects. Our findings suggest asymptomatic intestinal microsporidiosis is common in the study population, more than previously reported. In the study population, control measures need to be implemented, such as good personal hygiene, proper sanitation and safe drinking water supply. PMID- 27405128 TI - ASSOCIATION OF MEAN PLATELET VOLUME AND THE MONOCYTE/LYMPHOCYTE RATIO WITH BRUCELLA-CAUSED EPIDIDYMO-ORCHITIS. AB - We evaluated the association between the mean platelet volume (MPV) and monocyte/lymphocyte ratio (MLR) with brucella-caused epididymo-orchitis to determine if they could be used to differentiate between brucella and non brucella epididymo-orchitis. The charts of 88 patients with non-brucella and 14 patients with brucella epididymo-orchitis were retrospectively reviewed. Brucellosis was diagnosed by isolating Brucella spp from a blood culture or from a serum agglutination titer >= 1:160 along with accompanying clinical findings. The patients with brucella epididymo-orchitis were significantly more likely to have a lower MPV and a higher MLR than those with non-brucella epididymo orchitis. Using a MPV cut-off level of less than 9.25 fl to differentiate brucella from non-brucella epididymo-orchitis gives a sensitivity of 78.6%, a specifity of 78.4%, a positive predictive value of 36.7% and a negative predictive value of 95.8%. Using a MLR cut-off level of greater than 0.265 to differentiate brucella from non-brucella epididymo-orchitis gives a sensitivity of 71.4%, a specifity of 65.9%, a positive predictive value of 25% and a negative predictive value of 93.5.%. MPV and MLR values may assist in differentiating between brucella and non-brucella epididymo-orchitis. PMID- 27405129 TI - DIAGNOSTIC TEST OF SPUTUM GENEXPERT MTB/RIF FOR SMEAR NEGATIVE PULMONARY TUBERCULOSIS. AB - The objective of this study was to evaluate the performance of the Gene-Xpert MTB/RIF sputum test for diagnosing pulmonary tuberculosis (TB) among patients sputum acid-fast bacillus (AFB) smear negative results in Thailand, a country with a high prevalence of pulmonary tuberculosis. We studied 151 patients who presented to Srinagarind Hospital, Khon Kaen, Thailand with a 2 week or more history of fever and/or cough and an abnormal chest radiograph between 2010 and 2014; these patients had at least 2 negative sputum AFB smear results. Of these, 76 were diagnosed as having either confirmed or probable pulmonary TB: the 32 confirmed cases were those with a positive sputum culture for Mycobacterium tuberculosis (MTB) and the 44 probable case were those with clinical and radiographic findings consistent with TB and who had a response to anti-TB therapy. Seventy-five cases were diagnosed as not having pulmonary TB. Of the 32 patients with a positive sputum culture for MTB, 26 had a positive GeneXpert MTB/RIF sputum test. Compared to sputum culture for MTB the GeneXpert MTB/ RIF test gave a sensitivity of 83.9% (95% CI: 66.3-94.5) and a specificity of 92.1% (95% CI: 83.6-97), a positive predictive value (PPV) of 81.3% (95% CI: 63.6-92.8) and a negative predictive value (NPV) of 93.3% (95% CI: 85.1-97.8). The GeneXpert MTB/RIF test had a fair sensitivity and specificity for diagnosing smear negative pulmonary TB. It may be useful for diagnosing pulmonary TB in patients with a negative sputum AFB smear. The assay is faster than culture and can detect rifampicin resistant strains of MTB. PMID- 27405130 TI - DISTRIBUTION OF LEGIONELLA PNEUMOPHILA SEROGROUPS ISOLATED FROM WATER SYSTEMS OF PUBLIC FACILITIES IN BUSAN, SOUTH KOREA. AB - Legionella pneumophila is the major causes of legionellosis worldwide. The distribution of L. pneumophila was investigated in water systems of public facilities in Busan, South Korea during 2007 and 2013-2014. L. pneumophila was isolated from 8.3% of 3,055 samples, of which the highest isolation rate (49%) was from ships and the lowest 4% from fountains. Serogroups of L. pneumophila isolated in 2007 were distributed among serogroups (sgs) 1-7 with the exception of sg 4, while those of isolates during 2013 and 2014 included also 11 sgs ( 1, 2, 3, 4, 5, 6, 7, 8, 12, 13, 15). L. pneumophila sg 1 was predominated among isolates from fountains (75%), hotels (60%), buildings (44%), hospitals (38%), and public baths (37%), whereas sg 3 and sg 7 was the most prevalent from ships (46%) and factories (40%), respectively. The predominated serogroup of L. pneumophila isolates from hot and cooling tower water was sg 1 (35% and 46%, respectively), while from cold water was sg 3 (29%). These results should be useful for epidemiological surveys to identify sources of outbreaks of legionellosis in Busan, South Korea. PMID- 27405131 TI - PREVALENCE, ANTIBIOTIC AND PULSED-FIELD GEL ELECTROPHORESIS PATTERNS OF STAPHYLOCOCCUS AUREUS SMALL-COLONY VARIANTS IN CYSTIC FIBROSIS PATIENTS. AB - Staphylococcus aureus is the most common pathogen isolated from respiratory tract samples in cystic fibrosis (CF) cases. Rate of infection with S. aureus small colony variants (SCVs) also is increasing in CF patients. In this study, we aimed to determine the prevalence, antibiotic susceptibility and genotypic property of S. aureus SCVs in respiratory tract samples of CF patients admitted to Istanbul Faculty of Medicine Hospital, Turkey. Among 305 respiratory tract samples from 84 CF patients, normal S. aureus isolates were present in 71% of the CF patients and S. aureus SCVs in 21%. The highest antibiotic resistance was against penicillin (82%) followed by clarithromycin (21%) in S. aureus SCVs, while resistance to levofloxacin was low (2%) in normal S. aureus isolates but was 16% in S. aureus SCVs. No mecA and mecC were detected. The S. aureus strains constituted 24 different genotypes based on pulsed field gel-electrophoresis assay. The possible existence of S. aureus SCVs that are more resistant to antibiotis than normal S. aureus should be taken into considerstion when treating CF patients for this pernicious bacterial infection. PMID- 27405132 TI - NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE IN HEALTHY CHILDREN UNDER FIVE YEARS OLD IN CENTRAL LOMBOK REGENCY, INDONESIA. AB - Colonization with Streptococcus pneumoniae is mostly symptomless, but can progress to respiratory or even systemic disease. We investigated nasopharyngeal carriage of Streptococcus pneumoniae in healthy children under five years of age in Central Lombok Regency, Indonesia. This cross sectional study was carried out in 2012 among 1,200 healthy children aged 2 to 60 months. A multiplex sequential PCR was employed to determine serotype of cultured S. pneumoniae and a disk diffusion method to assess susceptibility to antimicrobial drugs. S. pneumoniae was cultured from 554 children and the most frequent serotypes found were 6A/B (22% of pneumococcal strains), 19F (11%), 23F (10%), 15B/C (8%), and 19A and 14 (4% each). The majority of strains were still susceptible to clindamycin (97%), erythromycin (87%), chloramphenicol (81%), and penicillin (72%), with only 41% and 38% susceptible to tetracycline and sulfamethoxazole/trimethoprim, respectively. Continuous surveillance of S. pneumoniae carriage is important for future pneumococcal vaccination programs in Indonesia. PMID- 27405133 TI - EPIDEMIOLOGY AND CONTROL OF THE FIRST REPORTED VANCOMYCIN-RESISTANT ENTEROCOCCUS OUTBREAK AT A TERTIARY-CARE HOSPITAL IN BANGKOK, THAILAND. AB - This retrospective study described the first reported vancomycin-resistant enterococci (VRE) outbreak from June 2013 through January 2014 at a tertiary-care hospital in Bangkok, Thailand. After the index case was detected in an 18-bed medical intermediate care unit, a number of interventions was implemented, including targeted active surveillance for VRE, strict contact precautions, enhanced standard precautions, dedicated units for VRE cases, extensive cleaning of the environment and the restricted use of antibiotics. VRE isolates were evaluated by polymerase chain reaction and random amplified polymorphic DNA (RAPD) testing. A prevalence case-control study was conducted. Among 3,699 culture samples from 2,671 patients screened, 74 patients (2.8%) had VRE. The positivity rate declined from 15.1% during week 1 to 8.2% during week 2 and then 1.4% during week 3. By weeks 4-9, the prevalences were 0-2.7%. However, the prevalence rose to 9.4% during week 10 and then subsequently declined. All VRE isolates were Enterococcus faecium and had the vanA gene. RAPD analysis revealed a single predominant clone. Multivariate analysis showed mechanical ventilation for >= 7 days was a predictive factor for VRE colonization [odds ratio (OR) 11.47; 95% confidence interval (CI): 1.75-75.35; p = 0.011]. This experience demonstrates VRE can easily spread and result in an outbreak in multiple-bed units. Active surveillance, early infection control interventions and rapid patient cohorting were important tools for control of this outbreak. Patients requiring mechanical ventilator for >= 7 days were at higher risk for VRE acquisition. PMID- 27405134 TI - CD4 LYMPHOCYTOPENIA WITHOUT HIV INFECTION. AB - The CD4 lymphocytes are an important part of the immune system. Besides HIV Infection, other conditions can cause a low CD4 count. We report the case of a 82 year-old female who presented with a markedly low CD4 count during a severe lower respiratory tract infection and respiratory failure without HIV infection. The total lymphocyte and the absolute CD4 counts are 255/mm3 and 109/mm3, respectively. Sputum and bronchial lavage fluid were both negative for acid-fast bacilli. The anti-HIV antibody test was negative.The blood culture was also negative. She had no history of diabetes, malnutrition or chronic kidney disease. Because pneumocystis jiroveci pneumonia could not be excluded, she was treated with a combination of clindamycin, dexamethasone, primaquine, meropenem and oseltamivir because of sulfamethoxazole drug allergy. One week later, she developed herpes simplex of her labia majora, so acyclovir was added. She had history of having a normal lymphocyte count during her routine yearly check-up. Her severe respiratory tract infection was associated with CD4 lymphocytopenia. PMID- 27405135 TI - COMPARISON OF GROWTH, INFECTIONS AND FEEDING HABITS AMONG FORMULA-FED INFANTS STARTING COMPLEMENTARY FEEDING AT 4 TO 6 MONTHS OLD WITH THOSE STARTING AT 6 MONTHS OLD. AB - The World Health Organization recommends starting complementary feeding among infants beginning at 6 months old, as opposed to 4 to 6 months old. We prospectively studied 21 formula-fed infants beginning complementary feeding at 4 to 6 months old and compared them with 20 formula-fed infants starting feeding at 6 months old to determine difference in growth, number of infections and feeding habits. The studied infants were each enrolled at age 4 months. The decision as to which group the infants were classified into was based on the parental decision as to when to start complementary feeding. Initial demographic data were obtained for each subject. Growth, infections, and feeding habit data were recorded. No significant differences in growth were detected between the 2 groups. Respiratory infections at age 10 to 12 months were more common among children who began complementary feeding later. By age 12 months, the percentages of subjects who were bottle feeding and night feeding, and new food acceptance were not different from each other, but those who began complementary feeding at age 6 months were less picky eaters. By 15 months old, those who began complementary feeding at age 6 months had less bottle feeding and better food acceptance. In conclusion, for formula-fed infants, age of onset of complementary feeding was not associated with infant growth or infection rates. However, some feeding habits differed between the two groups. It is unclear if the age of introducing complementary feeding caused these differences or was merely associated with these differences. PMID- 27405136 TI - SEXUAL PRACTICES AMONG MEN WHO HAVE SEX WITH MEN IN CHIANG MAI, THAILAND: PART OF THE ANTIRETROVIRAL PRE-EXPOSURE PROPHYLAXIS TRIAL. AB - This study aimed to gain a better understanding of the association between participation in a blinded antiretroviral pre-exposure prophylaxis (PrEP) clinical trial and sexual practices among men who have sex with men and transgender women. This study utilized both quantitative and qualitative methodologies. Data included reported PrEP medication adherence and sexual behavior among 114 study participants. Forty-six participants took part in qualitative data collection, 32 were interviewed and 14 participated in one of three focus group discussions. The average percentage of study medication adherence, number of sex partners and rates of sex without a condom were calculated. For qualitative data, content analysis was used to identify repeated normative themes, some of which arose spontaneously from interview interactions. Participants at the Chiang Mai site reported good adherence to the study medication. The sexual risk behavior of these participants had decreased by their final study visit; this was unrelated to level of adherence. Qualitative findings describe sexual practices that were highly contextual; participants used risk assessments to determine sex practices. Condoms were used with casual partners but not necessarily with primary partners. Our findings suggest that while PrEP is an exciting new development for HIV prevention, it must be paired with behavioral interventions to fully address sexual risk among this population. Interventions should provide this population with skills to negotiate condom use with their primary partners as well as in situations in which their sexual partners do not support condom use. PMID- 27405137 TI - AMBIENT PM10 AND PM2.5 CONCENTRATIONS AT DIFFERENT HIGH TRAFFIC-RELATED STREET CONFIGURATIONS IN BANGKOK, THAILAND. AB - This study investigated the potential exposure levels of PM10 and PM2.5 at two different road configuration sites in Bangkok, Thailand: covered and open roadside areas. One hundred samples were collected together with the meteorological data: temperature, relative humidity, wind speeds, and solar radiation. Spearman rank correlation was used to analyze the relationships between these factors, and PM10 and PM2.5 levels at different roadside areas. The PM10 and PM2.5 levels at the covered area were 1.72 and 1.60 times more than those levels at open area were. The mean levels were found to be 154.59 and 94.42 ug/m3 at the covered areas, and 89.43 and 58.69 ug/m3 at the open areas. These results suggested that a higher potential risk for workers, such as street vendors, was the exposure to particulate matters at the covered areas compared to open areas. Wind speeds and relative humidity were significantly negative-related influencing factors on PM10 and PM2.5 levels at the open area, but not significantly related for the covered areas. PMID- 27405138 TI - TOBACCO AND ALCOHOL USE AMONG CHRONIC DISEASE PATIENTS IN CAMBODIA, MYANMAR AND VIETNAM. AB - The aim of this study was to explore the prevalence of tobacco and alcohol use and to determine the factors associated with tobacco and alcohol use among chronic disease patients in Cambodia, Myanmar and Vietnam. A cross-sectional survey was conducted among 4,803 adult chronic disease patients (mean age 49.3 years; SD=16.5) recruited systematically from health facilities. Fifteen point five percent of those studied were current smokers, 14.5% current smokeless tobacco users, 20.7% daily tobacco users (smokers or smokeless tobacco), 9.3% problem drinkers and 4.1% both daily tobacco users and problem drinkers. Having been diagnosed with hypertension, chronic obstructive pulmonary disease (COPD), liver disease, and dyslipidemia were positively associated with daily tobacco use; liver disease, gout and other musculoskeletal conditions, kidney disease, and dyslipidemia were positively associated with problem drinking. On multivariate logistic regression analysis, socio-demographics (being male, older age, lower education, coming from Myanmar, being single, divorced or widowed, rural residence and part-time employed), problem drinking and having two or more chronic health conditions were associated with daily tobacco use. Socio demographics (being male, younger age, coming from Vietnam, being married or cohabiting), daily tobacco use and not having depressive symptoms were found to be associated with problem drinking. High prevalences of daily tobacco use and problem drinking were found among chronic disease patients and several socio demographic, disease specific, and other health risk behavior factors were identified which can guide substance use intervention programs for this population. PMID- 27405139 TI - PHYSICAL ACTIVITY, SELF-ESTEEM, AND QUALITY OF LIFE AMONG PEOPLE WITH PHYSICAL DISABILITY. AB - Physical activity (PA) can improve health and quality of life (QOL) of healthy people. However, the association between PA and QOL among people with physical disability (PWPD) is inconclusive. This study was conducted to determine the relationships between factors including intensity of PA, activitiy in daily living (ADL), stress, and self-esteem that influences self-reported QOL among PWPD. The relationships were further explored using the in-depth interview method to find out whether the intensity of PA, stress, and self-esteem are related to QOL perception in PWPD. One hundred sixty PWPD aged 18-48 years who studied at a vocational school were enrolled. A mixed method case study was conducted: cross sectional survey and in-depth interview. Five questionnaires, including the Barthel Index, Perceived Stress Scale (PSS), Rosenberg Self-Esteem Scale (RSES), and Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) were distributed. QOL was measured using the WHOQOL_BREF. Multiple linear regression was used to determine factors for QOL prediction. For in-depth interview, ten persons from each group (poor-to-fair and good QOL) volunteered to explore further about life satisfaction related to physical disability. One hundred forty-six (91%) subjects completed all questionnaires. One hundred fourteen (77%) reported poor-to-fair QOL. QOL was explained by self-esteem and ADL (adjusted R2 34.7%, p < 0.001) after adjusted for age, stress, and PA. Although PA could not explain QOL in PWPD, good QOL reported high activities (28.40 +/- 30.20 MET hour/day) compared to poor and fair QOL (17.94 +/- 22.06 and 21.70 +/- 17.75 MET hour/day). Those who had good QOL reported that they were proud to be independent and did not feel inferior. PA participation among people with disabilities should therefore be encouraged. PMID- 27405140 TI - [Not Available]. PMID- 27405141 TI - [EVALUATION OF THE PERCEPTION OF RISK IN THE NURSING STAFF IN CARE OF PATIENTS WITH SUSPECTED BIOLOGICAL HAZARD]. AB - INTRODUCTION: Healthcare personnel is especially vulnerable to the risks derived from their job. The complexity that has the care of patients with Ebola justifies the study of the perception of risk of such professionals. OBJECTIVE: To know the perception of risk in the nursing staff that takes care of patients suspected of suffering the Ebola virus. MATERIAL AND METHODS: Transversal study carried out in the Hospital Clinic of Barcelona. 19 professionals of nursing staff that attended suspected Ebola patients were included in the study. The data was collected through a questionnaire of dimensional evaluation of the perceived risk along with sociodemographic variables and a subsequent statistics analysis. RESULTS: A percentage of 68% of the nursing staff refereed having a high level of knowledge of the risk associated with the factor of this study. A percentage of 42% determined that there was a very high possibility of being harmed. A percentage of 63% considered that the most harmful consequences would appear in short term, and finally a percentage of 48% considered that there was a very high risk of accident or illness associated to the factor of this study, whereas a percentage of 5% considered the risk to be very low. CONCLUSIONS: The answers obtained showed not only that nursing staff had a very high level of knowledge regarding the risk associated to the factor of this study, but also that the emotional fear was very high. PMID- 27405142 TI - [Not Available]. PMID- 27405143 TI - [THERAPEUTIC LIMITATION OF INTENSIVE CARE UNIT]. AB - The therapeutic limitation is a relatively common in Intensive Care Units practice. There are different types of therapeutic limitation, and the patient can be classified according to measures likely to withdraw or not start. Among such measures include removal of stand mechanical ventilation with the analgesia and sedation applied to the end of life of the patient. PMID- 27405144 TI - [ESTIMATE OF THE INTRINSIC ERROR OF THE MEASURING INSTRUMENT OF THE LABORATORY FOR ANALYTICAL DETERMINATIONS OF THE CRITICAL PATIENT]. AB - Decrease blood loss associated with the analytical laboratory is a determinant of safety and quality in the preanalytical phase, in order to achieve an optimal level of care, where nurses have leading role to be responsible for the care of the critically ill patient. PMID- 27405145 TI - [INFLUENCE OF DIET IN PRIMARY PREVENTION OF GASTRIC CANCER, IN PATIENTS INFECTED WITH HELICOBACTER PYLORI]. AB - INTRODUCTION: Helicobacter pylori infection is the main risk factor for developing gastric cancer, with the influence of genetic, toxic and dietary factors. It is the fourth most common cancer and the second most deadly worldwide, so its prevention is important specially focusing on dietary habits, to be approached from the primary care setting. AIM: Evaluate the influence of diet on the primary prevention of gastric cancer in patients with Helicobacter pylori infection. METHODS: Systematic review, the keywords "Helicobacter pylori", "diet" and "stomach neoplasms" were previously selected from the DeCS and MeSH structured vocabulary. Sources of primary and secondary databases were consulted, limits were established. RESULTS: H. pylori infection and dietary factors may act synergistically in the development of gastric cancer and some cooking practices. Dietary factors may increase the risk of gastric cancer like the high consumption of salt, salty foods, saturated fat, red and processed meats, while fruits and vegetables may be considered as a protective factor, especially the high consumption of Allium and the cruciferous family. CONCLUSIONS: The lifestyle and dietary habits may influence the development of gastric cancer, especially in patients with H. pylori infection. Decreasing consumption of salty, processed, smoked or pickled foods, red meat and saturated fat, avoiding toxins, and carrying out a diet rich in fruits and vegetables, in addition to eradicating the bacteria, can be considered the most effective preventive strategy against the risk of developing gastric cancer. PMID- 27405146 TI - [PREVALENCE OF THE STREPTOCOCUS AGALACTIAE IN THE PREGNANT WOMAN FROM THE AUTONOMIC CITY OF MELILLA: IS CULTURE A DETERMINANT FACTOR?]. AB - BACKGROUND: The neonatal infection by Streptococcus group B is one of the main causes of neonatal morbi-mortality rate. For this reason a screening is made to each pregnant woman in order to detect its presence, and if it was the case, to apply an antibiotic treatment during labour. The aim of this study was to know the prevalence of this Streptococcus in the pregnant women from Melilla, as well as the differences according to culture and age. METHOD: A descriptive cross sectional study located in the Hospital Comarcal from Melilla. RESULTS: The sample is taken from 280 women: 194 are from Muslim culture (69.3%), 68 are from Christian culture (24.3%) and 18 women from unknown cultures (6.4%). Also it is known that 78 of them are 25 years old or less (27.85%), 158 are between 26 and 34 years old (56.42%) and 44 are 35 years old or more (15.71%). CONCLUSIONS: The prevalence of vagino-rectal colonization by Streptococcus group B in the pregnant women from Melilla is within the national estimated figures, however it is different if they are from Muslim or Christian culture, being higher in the Muslim population. On one hand both prevalences are within the national statistics, and on the other hand it is observed that there is not any difference according to age. PMID- 27405147 TI - [HUMAN RESOURCES MANAGEMENT BASED ON COMPETENCIES]. AB - We are living in a time with a lot of changes in which health organizations have more challenges to face. One of them is to recognize, strengthen, develop and retain the talent they have. Competency-based human resources management is emerging as a tool that contributes to achieve that aim. Competencies from the generic or characteristic perspective: personality traits, values and motivations, which are deeply rooted in the person. Through elaborating a competencies map for the organization, and identifying the job competencies profile, above all in key jobs, the employees know what it is going to expect from them. After, detect and cover the learning needs, it is possible to achieve better adjust between worker-job. The nursing unit manager is a key job because it is a link between management team and nursing team. The way that it is performed, it will have impact on the quality of care and its team motivation. So, the most adequate person who covers this job would have a part of knowledge, skills, attitudes and compatible interests with her job. Competency-based management helps identify both the potential and learning needs to performing this job. PMID- 27405148 TI - [HAND HYGIENE BELIEFS AND PERCEPTIONS OF NURSING STUDENTS]. AB - OBJECTIVE: A key element to promote the compliance of hand hygiene (HH) among health care workers (HCWs) is to analyze their perceptions of it. Our objective was to evaluate the beliefs and perceptions that nursing students have on HH. METHOD: A cross-sectional study was performed during the 2011-2012 school year. It included all enrolled nursing students from a Spanish University. The information was obtained by a self-administered questionnaire, which assessed the importance of HH to control nosocomial infections (NI), beliefs (by Hand Hygiene Beliefs Scale-HHBS) and perceptions of the importance given to HH in the curriculum (by Hand Hygiene Importance Scale-HHIS). Associations were analyzed using logistic regression. RESULTS: 146 students of the 270 (54.1%) completed the questionnaire. Assessing the importance of HH as NI control measure ranged from 4 to 10 points (median = 9). The more agreement HHIS item was to consider HH as an important part of the curriculum (76.1%), while HHBS item was to believe that hands washing after going to the toilet reduces the transmission of infectious diseases (100%). Importance of HH to control NI valued with > 9 points was associated with the agreement to consider it as an relevant part of the curriculum (OR:2.5), and to believe that HCWs play an important role in preventing NI (OR: 4.3). CONCLUSIONS: HH was rated as an important NI control measure. Educational programs should be carried out at universities to students do HH, whether they observe poor compliance among HCWs in their practices. PMID- 27405149 TI - [SAFETY IN THE ELDERLY: HOME ACCIDENTS]. AB - Home accidents are more common in the elderly and they can have serious consequences to the injured person's health. At home, chances to suffer accidents of any type are higher, because it's the place where old people spend most of their daily time. It is important to point out that a high percentage of domestic accidents could be easily avoided by taking some simple cautions. The main aim of this paper is to know how we can prevent most common domestic accidents in the aged population: falls, burnings, poisonings and fire prevention. PMID- 27405150 TI - [Not Available]. PMID- 27405151 TI - [Not Available]. PMID- 27405152 TI - [Not Available]. PMID- 27405153 TI - [Not Available]. PMID- 27405154 TI - [Non-autophagic degradation roles of autophagy receptors]. AB - A growing body of evidence has indicated the important role of autophagy receptors in directing ubiquitinated or non-ubiquitinated cargos towards autophagy. Autophagy receptors bind to LC3 (microtubule-associated protein 1 light chain 3) on phagophore and autophagosome membranes, and recognize signals on cargoes in the delivery system of autophagy. However, the diverse domains in the receptor structures determine that their roles would never be limited to autophagy. Up to date, increasing numbers of the receptor proteins have been demonstrated to serve as a molecular link or switch participating in autophagic degradation, apoptosis or cell survival signals. Here, we highlight the non autophagic roles of these receptor proteins to draw attention to this growing research topic. PMID- 27405155 TI - [Autophagy pathways and key drug targets in Parkinson's disease]. AB - Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging. Great progresses have been made toward understanding the pathogenesis over the past decades. It seems that both genetic factors and environmental factors contribute to PD, while the precise pathogenesis still remains unknown. Recently, increasing evidence has suggested that autophagy dysregulation is closely related to PD. Dysregulation of the autophagic pathways has been observed in the brains of PD patients or in animal models of PD, and a number of PD-associated proteins, such as a-synuclein, Parkin and PINK1, were found to involve in autophagy, suggesting a link between autophagy and pathogenesis of PD. In this review, we summarized the role of PD-associated proteins in autophagy pathways. In addition, we described the efficacy of autophagy-modulating compounds in PD models and discussed promising strategies for PD therapy. PMID- 27405156 TI - [Effects of resveratrol-induced cellular autophagy in control of neurodegenerative diseases]. AB - Cellular autophagy is a major degradative pathway for clearance of aggregate prone proteins and damaged organelles. It plays an important role in regulating cellular homeostasis, cell growth and development, and disease development. Dysfunctional autophagy contributes to the pathology of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, in which specific pathological protein accumulation occurs. A growing body of evidence suggests that resveratrol plays a significantly role in the regulation of autophagy and clearance of pathological proteins. Resveratrol is a potential drug for neurodegenerative diseases therapy. This review focuses on the effects of resveratrol on cellular autophagy and clinical application in the control of neurodegenerative diseases. PMID- 27405157 TI - [The regulatory role of autophagy in tumor process]. AB - Autophagy is a classical regulatory mechanism of energy metabolism and self update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy. PMID- 27405158 TI - [Study on the regulation of autophagy against anticancer drugs' toxicity]. AB - Autophagy is a crucial biological process in eukaryotes, which is involved in cell growth, survival and energy metabolism. It has been confirmed that autophagy mediates toxicity of anticancer drugs, especially in heart, liver and neuron. It is important to understand the function and mechanism of autophagy in anticancer drugs-induced toxicity. Given that autophagy is a double-edged sword in the maintenance of the function of heart, liver and neuron, the autophagy-mediated toxicity are very complicated in the body. We provide a review on the concept of autophagy and current status about autophagy-mediated toxicity of anticancer drugs. The knowledge is crucial in the basic study of anticancer drugs-induced toxicity, and provides some strategies for the development of alleviating the toxicity of anticancer drugs. PMID- 27405159 TI - [Molecular markers of autophagy]. AB - Autophagy is a physiological process which delivers the mutant cytoplasmic proteins and dysfunctional subcellular organs into lysosomes for degradation to generate fuel in the deficiency conditions. It is mainly classified into macroautophagy, microautophagy and chaperon-mediated autophagy (CMA), as well as the selective autophagy such as mitophagy and aggrephagy. This review mainly introduces the key molecular markers of macroautophagy, CMA and mitophagy. PMID- 27405160 TI - [Morphological analysis of autophagy]. AB - Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional subcellular organelles and proteins in all living cells. The process of autophagy can be divided into three relatively independent steps: the initiation of phagophore, the formation of autophagosome and the maturation/degradation stage. Different morphological characteristics and molecular marker changes can be observed at these stages. Morphological approaches are useful to produce novel knowledge that would not be achieved through other experimental methods. Here we summarize the morphological methods in monitoring autophagy, the principles in data interpretation and the cautions that should be considered in the study of autophagy. PMID- 27405162 TI - [Progress of autophagy screening systems]. AB - Autophagy is an active research area in the biomedical field as its role has been identified in many physiological and pathological processes. Accordingly, there is a growing demand to identify, quantify and manipulate the process accurately. Meanwhile, there is great interest in identifying compounds that modulate autophagy because they may have applications in the treatment of a variety of autophagy-related diseases. In this review, we summarize the current status of autophagy screening systems to facilitate identification of autophagy modulators. PMID- 27405161 TI - [New methods to detect autophagic flux]. AB - Autophagy is a crucial biological process of eukaryotes, which is involved in cell growth, survival and energy metabolism, while the premise of the autophagy function is activated autophagic flux. It has been confirmed that impaired autophagic flux promotes pathogenesis of many chronic inflammatory diseases, especially cancer, neurodegenerative disease and tissue fibrosis, therefore the analysis of autophagic flux state is important for revealing autophagy function and the mechanism of autophagy related diseases. Given that autophagy is a dynamic process with multiple steps, it is very hard to observe the real state of autophagic flux. Summarized here is the novel concept and current approach to detect autophagic flux. This knowledge is crucial for the researching of the biological function of autophagy, and may provide some strategies for developing autophagy-related drug. PMID- 27405163 TI - [Sodium nitrite enhanced the potentials of migration and invasion of human hepatocellular carcinoma SMMC-7721 cells through induction of mitophagy]. AB - Nitrites play multiple characteristic functions in invasion and metastasis of hepatic cancer cells, but the exact mechanism is not yet known. Cancer cells can maintain the malignant characteristics via clearance of excess mitochondria by mitophagy. The purpose of this article was to determine the roles of nitrite, reactive oxygen species (ROS) and hypoxia inducing factor 1 alpha (HIF-1 alpha) in mitophagy of hepatic cancer cells. After exposure of human hepatocellular carcinoma SMMC-7721 cells to a serial concentrations of sodium nitrite for 24 h under normal oxygen, the maximal cell vitality was increased by 16 mg x (-1) sodium nitrite. In addition, the potentials of migration and invasion for SMMC 7721 cells were increased significantly at the same time. Furthermore, sodium nitrite exposure displayed an increase of stress fibers, lamellipodum and perinuclear mitochondrial distribution by cell staining with Actin-Tracker Green and Mito-Tracker Red, which was reversed by N-acetylcysteine (NAC, a reactive oxygen scavenger). DCFH-DA staining with fluorescent microscopy showed that the intracellular level of ROS concentration was increased by the sodium nitrite treatment. LC3 immunostaining and Western blot results showed that sodium nitrite enhanced cell autophagy flux. Under the transmission electron microscopy (TEM), more autolysosomes formed after sodium nitrite treatment and NAC could prevent autophagosome degradation. RT-PCR results indicated that the expression levels of COX I and COXIV mRNA were decreased significantly after sodium nitrite treatment. Meanwhile, laser scanning confocal microscopy showed that sodium nitrite significantly reduced mitochondrial mass detected by Mito-Tracker Green staining. The expression levels of HIF-1alpha, Beclin-1 and Bnip3 (mitophagy marker molecular) increased remarkably after sodium nitrite treatment, which were reversed by NAC. Our results demonstrated that sodium nitrite (16 mg x L(-1)) increased the potentials of invasion and migration of hepatic cancer SMMC-7721 cells through induction of ROS and HIF-1alpha mediated mitophagy. PMID- 27405164 TI - [Correlation between autophagy and polarization of macrophages in atherosclerosis plaque in arteriosclerosis obliterans amputees]. AB - This study was designed to investigate the correlation between autophagy and polarization of macrophages in atherosclerosis (AS) plaque in arteriosclerosis obliterans amputees. Femoral artery specimens from arteriosclerosis obliterans amputees were performed hematoxylin and eosin (HE) staining, oil red O and immunofluorescence staining to observe the morphology of atherosclerotic plaque, phenotype of macrophages and autophagy in plaque; using real-time quantitative RT PCR technology to detect the mRNA level of M1 and M2 type markers in arterial tissue; to analyze polarized signal pathway and autophagy protein levels in macrophages by Western blotting. Arterial specimens staining showed obvious lipid deposition and obvious infiltration of amount of foam cells and inflammatory cells. Macrophages were mainly expression M1 type in percentage in fibrous plaque. Although both M1 and M2 macrophages were upregulated in atheromatous plaque, the increase was dominant in M2 type in percentage. The level of autophagy was significantly higher in the atheromatous plaque than that of fibrous plaque. The expression of tumor necrosis factor- alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and interleukin-12 (IL-12) mRNA was significantly higher in fibrous plaque than that of atheromatous plaque (P < 0.01 or 0.05), and arginase 1 (Arg-1), transforming growth factor-beta (TGF-beta), CD163 and interleukin-10 (IL-10) mRNA was significantly lower than that in atheromatous plaque (P < 0.01). The levels of p-STAT1 and NF-kappaB were significantly increased in fibrous plaque (P < 0.01), while p-STAT6 expression was significantly increased in atheromatous plaque (P < 0.01). The level of LC3-II was significantly higher in atheromatous plaque than that in fibrous plaque (P < 0.01). Macrophages in early atherosclerotic plaque were induced to M1 type through p-STAT1/NF-kappaB pathway and expressed moderate levels of autophagy; while macrophages in advanced plaques were induced to polarization of M2 type through p-STAT6 pathway. M2 macrophages expressed a higher level of autophagy than M1 macrophages. PMID- 27405165 TI - [OATP1B1 in drug-drug interactions between traditional Chinese medicine Danshensu and rosuvastatin]. AB - The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-infinity) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 MUmol x L(-1) Danshensu. The IC50 parameters was (53.04 +/- 2.43) MUmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 +/- 4.94)% and (63.61 +/- 3.94)%, respectively, by Danshensu at 1 and 10 MUmol x L(-1). While transport of rosuvastatin was reduced by (8.22 +/- 2.40)% and (11.56 +/- 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence. PMID- 27405166 TI - [Construction and function identification of luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR]. AB - This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3 vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity. PMID- 27405167 TI - [Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats]. AB - The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg( 1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, beta-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG. PMID- 27405168 TI - [Synthesis, biological activity and molecular docking research of N-{[(4-oxo thiochroman-3-yl)phenyl]-methyl}acetamide derivatives as alpha-glucosidase inhibitors]. AB - In order to develop potent antidiabetic agents that have inhibitory effect to a glucosidase, twelve beta-acetamido ketone derivatives such as N-{[(substituted-4 oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro alpha-glucosidase inhibition assays of compounds 4a-41 were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of alpha glucosidase at the concentration of 5.39 mmol x L(-1). The structure-activity relationship of these beta-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and alpha-glucosidase. Our results will be helpful for designing of alpha-glucosidase inhibitors in the future. PMID- 27405169 TI - A new caffeate compound from Nardostachys chinensis. AB - A new caffeate compound, (E)-erythro-syringylglyceryl caffeate (1), was isolated from the roots and rhizomes of Nardostachys chinensis Batal., together with nine known phenolic compounds, including (+)-licarin A (2), naringenin 4', 7-dimethyl ether (3), pinoresinol-4-O-beta-D-glucoside (4), caraphenol A (5), Z-miyabenol C (6), protocatechuic acid (7), caffeic acid (8), gallic acid (9) and vanillic acid (10). Their chemical structures were elucidated on the basis of spectroscopic data and physicochemical properties. Furthermore, this is the first report of compounds 2, 5 and 6 from Nardostachys genus. PMID- 27405170 TI - [Identification of 3-demethylchuangxinmycin from Actinoplanes tsinanensis CPCC 200056]. AB - Chuangxinmycin (CM) from Actinoplanes tsinanensis was an antibiotic discovered by Chinese scientists about 40 years ago. It contains a new heterocyclic system of indole fused with dihydrothiopyran, whose biosynthetic mechanism remains unclear. CM is used as an oral medicine in the treatment of bacterial infections in China. The simple structure makes CM as an attractive candidate of structure modification for improvement of antibacterial activity. Recently, we analyzed the secondary metabolites of Actinoplanes tsinanensis CPCC 200056, a CM producing strain, as a natural CM analogue. We discovered the first natural CM analogue 3 demethylchuangxinmycin (DCM) as a new natural product. Compared to CM, DCM exhibited a much weaker activity in the inhibition of the bacterial strains tested. The finding provides valuable information for the structure-activity relationship in the biosynthesis of CM. PMID- 27405171 TI - [Simultaneous determination of 11 mycotoxins in malt by isotope internal standard UPLC-MS/MS]. AB - A suitable ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of 11 mycotoxins with isotope internal standard in malt. The mycotoxins in malt were extracted and purified by one-step ultrasonic extraction procedure using acetonitrile/water/acetic acid (80 : 19 : 1), and then detected and confirmed by UPLC-MS/MS, and quantified by isotope labeled AFB1 ([13C17]-AFB1) and ZEN ([13C18]-ZEN) internal standards. Rapid separation of the 11 mycotoxins was successfully achieved on a Phenomenex Kinetex C18 column (100 mm x 2.1 mm, 2.6 MUm) with gradient elution using the mobile phase of methanol containing 0.1% formic acid and 2 mmol x L(-1) ammonium acetate in water. Simultaneous acquisition was performed in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI) source operated in both positive and negative ionization modes. The established method provided a good linearity for the 11 mycotoxins within their respective linear ranges with correlation coefficients all higher than 0.999 1. The average recoveries ranged from 75.0% to 117.0% with relative standard deviations (RSDs) below 5.1%. The limits of detection (LODs) and quantitation (LOQs) ranged from 0.05 to 30 MUg x kg(-1) and 0.15 to 87.5 MUg x kg(-1), respectively, which were below the maximum residue levels (MRLs) set by the European Union. Twenty malt samples were analyzed and nine samples were detected with mycotoxins, which were confirmed according to the same fragment ions found in positive samples and the standards at the same retention time. This study has demonstrated that the one-step extraction procedure of mycotoxins from complex matrices coupled to UPLC-MS/MS method is simple, quick, accurate and sensitive for quantitative and qualitative analysis of multiple mycotoxins in malt. PMID- 27405172 TI - [Influence of metal ions on stability of 2,3,5,4'-tetrahydroxy stilbene-2-O-beta D-glucoside contained in Polygoni Multiflori Radix]. AB - Decoction is one of the most commonly used dosage forms of traditional Chinese medicine. The stability of chemical constituents in decoction is closely related to the clinical efficacy and safety. There were few reports about the influence of metal ions in the stability of chemical constituents in traditional Chinese medicine. However, there is no evidence that metal ions in decoction water need to be controlled. In this study, 2,3,5,4'-tetrahydroxy stilbene-2-O-beta-D glucoside (THSG), one of the main constituents in Polygoni Multiflori Radix was studied. Ordinary tap water, deionized water, and water containing different metal ions were used to investigate and compare the influence on THSG. The results showed that after storage in a dark place at the room temperature for 10 days, the degradation of THSG was 7% in deionized water, while undetectable in tap water. The content of THSG could be decreased by different kinds of metal ions, and the effect was concentration-dependent. Moreover, Fe3+ and Fe2+ showed the greatest influence at the same concentration; and our study has shown that THSG decreased more than 98% in Fe and Fe2+ solutions at 500 ppm concentration. In the same time we found out p-hydroxybenzaldehyde (molecular weight: 122.036 7) and 2,3,5-trihydroxybenzaldehyde-2-O-glycoside (molecular weight: 316.079 4) were the main degradation products of THSG in tap water and water containing Cu2+, Ca2+, Zn2+, Mg2+ and Al3+. The product of THSG dimer with a water molecule was found in water containing Fe3+ and Fe2+. The above results showed that the metal ions in water could significantly influence the stability of THSG in water, indicating that the clinical efficacy and safety of decoction would be affected if the metal ions in water were not under control. It's suggested that deionized water should be used in the preparation of decoction containing Polygoni Multiflori Radix in the clinic to avoid degradation of THSG. Meanwhile, decoction prepared by tap water should be taken by patients in a short time. Our investigation provides important information and reference about the influence of metal ions on the stability of decoctions in other traditional Chinese medicine that have unstable groups such as hydroxyls and unsaturated bonds, etc. PMID- 27405173 TI - [Degradation kinetics of chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid at neutral and alkaline pH values]. AB - The degradation kinetics of chlorogenic acid (5-CQA), cryptochlorogenic acid (4 CQA), and neochlorogenic acid (3-CQA) in aqueous solution at 37 degrees C and different pH values (7.05, 7.96, 9.25) were investigated in the present work. The results indicated that 3-, 4- and 5-CQA tended to remain stable in acidic pH circumstance, and unstable in neutral and alkaline pH circumstance. With the increase of the alkalinity, the degradation of 3-, 4- and 5-CQA was increased leading to a less amount of total CQA and was satisfactorily described by the Weibull equation. Meanwhile, caffeic acid was not detected after the degradation of CQA. Moreover, the degradation of 3-CQA and 5-CQA tended to be converted to 4 CQA, and the degradation of 4-CQA tended to be converted to 3-CQA rather than 5 CQA. The comparison of the degradation kinetics parameters of 3-, 4- and 5-CQA at neutral and alkaline pH values showed that the orders of the rate constant (k) values were 4-CQA > 3-CQA > 5-CQA, while the orders of the degradation half life (t1/2) values were 4-CQA < 3-CQA < 5-CQA, indicating the orders of the stabilities of 3-, 4- and 5-CQA at 37 degrees C and neutral and alkaline pH values were 4-CQA < 3-CQA < 5-CQA. PMID- 27405174 TI - [Correlation between integrated pharmacokinetics and pharmacodynamics of bile processed Rhizoma Coptidis in febrile rats]. AB - This study was designed to validate the correlation between integrated pharmacokinetic and therapeutic effects of alkaloids using bile processed Rhizoma Coptidis (BRC). Rats were divided into three groups: normal, disease model, model+BRC. Rats were induced to have an excessive heat syndrome. Rectal temperatures were collected at 0, 3, 6 and 9 h after single oral administration of the drugs. The plasma concentrations of three alkaloids were quantified at different times by UPLC-MS/MS after the administration of BRC. An approach of self-defined weighting coefficiency was created to the holistic pharmacokinetic profiles of alkaloids in BRC. The classified and integrated synthetic concentrations were obtained, and then the pharmacokinetic parameters of alkaloids were calculated from non-compartmental model analysis. The potential relationship between the integrated mean concentration of alkaloids and the antifebrile efficacy was investigated. The holistic t(max) of alkaloids was 1.11 h, the antifebrile effect of BRC at 3 h was improved over the model group. Double peaking appeared in the integrated blood concentration-time curve, the second t(max) of alkaloids was 4.82 h. The antifebrile effects of BRC at 3-6 h were significant, and the antifebrile effects at 6-9 h was decreased significantly. Dynamic variation of alkaloids of BRC in the body exhibited the similarity to the pattern of its antifebrile effect. PMID- 27405175 TI - [Preparation and evaluation of intra-articular injectable sinomenine hydrochloride-loaded in situ liquid crystals]. AB - Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV2). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV2. In situ hexagonal liquid crystals (ISH2) were prepared based on the composition of ISV2 with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV2 and ISH2 in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV2 and ISH2 were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH2 in adjuvant induced arthritis rats. The optimal ISV2 (PT/ET/water, 64 : 16 : 20, w/w/w) loaded with 6 mg x g(-1) of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV2 was able to sustain the drug release for 144 h. The optimal ISH2 system was prepared by addition of 5% VitEA into PT in the optimal ISV2 system. This ISH2 (PT/VitEA/ET/water, 60.8 : 3.2 : 16 : 20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH2 was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC(0-infinity) of ISH2 group were increased significantly compared with that of SMH solution group and the AUC(0 infinity) of ISH2 group was 6.01 times higher than that of SMH solution group. The developed ISH2 was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis. PMID- 27405176 TI - [Relation between drug release and the drug status within curcumin-loaded microsphere]. AB - To study the relation between drug release and the drug status within curcumin loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 +/- 0.21)%, (11.71 +/- 0.39)%, (15.41 +/- 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 +/- 0.64)% and (5.66 +/- 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres. PMID- 27405177 TI - [Evaluation of genetic diversity and population structure of Bletilla striata based on SRAP markers]. AB - Bletilla striata has been used as traditional Chinese medicine for several centuries. In recent years, the quality and quantity of wild B. striata plants have declined sharply due to habitat deterioration and human over-exploitation. Therefore, it is of great urgency to evaluate and protect B. striata wild plant resource. In this study, sequence-related amplified polymorphism (SRAP) markers were applied to assess the level and pattern of genetic diversity in twelve populations of B. striata. The results showed a high level of genetic diversity (PPB = 90.48%, H = 0.349 4, I = 0.509 6) and moderate genetic differentiation among populations (G(st) = 0.260 9). Based on the unweighted pair-group method with arithmetic average (UPGMA), twelve populations gathered in three clusters. The cluster 1 included four populations. There are Nanjing, Zhenjiang, Xuancheng and Hangzhou. The seven populations which come from Hubei Province, Hunan Province, Jiangxi Province and Guizhou Province belonged to the cluster 2. The cluster 3 only contained Wenshan population. Moreover, Mantel test revealed significant positive correlation between genetic distances and geographic distances (r = 0.632 9; P < 0.000 1). According to the results, we proposed a series of conservation consideration for B. striata. PMID- 27405178 TI - [Induction of rat hepatic CYP2E1 expression by arecoline in vivo]. AB - The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg( 1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human. PMID- 27405179 TI - Looking forward. PMID- 27405180 TI - Progress in achieving universal access to surgical care: An update and a path forward. PMID- 27405182 TI - Stay connected and informed: Start tweeting. PMID- 27405181 TI - The surgeon and social media: Twitter as a tool for practicing surgeons. PMID- 27405183 TI - 2015 ACS Governors Survey: Surgeons speak out on GME funding issues. PMID- 27405184 TI - Early ICD-10 audits indicate a learning curve for general surgeons. PMID- 27405185 TI - JACS CME and the ACS NSQIP Surgical Risk Calculator. PMID- 27405187 TI - NTDB DATA POINTS: Biting the hand that feeds you. PMID- 27405186 TI - Support surgical time outs on National Time Out Day--and all year long. PMID- 27405188 TI - Study shows micro breaks have big benefits. PMID- 27405189 TI - ACS-Military Health System Partnership focuses on surgeon readiness and sustaining trauma systems. PMID- 27405190 TI - Change Your Tribe: Change Your Life. PMID- 27405191 TI - Helping Nursing Students Develop and Expand Their Emotional Intelligence. PMID- 27405192 TI - Providing Hands-on Experiences in Health Care Research to Mentor New Research Scholars. AB - AIM: This article describes the benefits of integrating students into a National Institutes of Health-funded research project. BACKGROUND: Research is important in all academic disciplines for increasing knowledge and determining the effectiveness of currently used interventions. Educating nursing students to read, evaluate, and use research in practice is essential for solving complex health care challenges and achieving better patient outcomes METHOD: The students were involved at all levels of the research process: project development, site acquisition, recruitment of participants, data collection and analysis, and manuscript development. Interviews of the student researchers were conducted to understand the students' experience of participation in the research study. RESULTS: Three themes were identified: creating new knowledge is worthwhile, research is interesting and meaningful, and research can shape practice. CONCLUSION: Promoting knowledge and experience by involving students in research projects can create a bridge to the development of evidence-based practice. PMID- 27405193 TI - Baccalaureate Minority Nursing Students Perceived Barriers and Facilitators to Clinical Education Practices: An Integrative Review. AB - AIM: This integrative review synthesized baccalaureate minority nursing students' perceptions of their clinical experiences. BACKGROUND: The diversity of the nursing workforce does not mirror the United States population. Attrition rates of minority nursing students remain higher than rates for White students. Literature examining facilitators and barriers to minority student success predominantly focuses on academic factors, excluding those relevant to clinical education. METHOD: An integrative review using literature from nursing and education. FINDINGS: Three common perceived barriers were identified: discrimination from faculty, peers, nursing staff, and patients; bias in faculty grading practices; and isolation. CONCLUSION: Although little is known about the relationship between clinical failures and overall attrition, this review provides evidence that minority students encounter significant barriers in clinical education. To increase the diversity of the nursing workforce, faculty must address these issues and make modifications to ensure an equal opportunity at a quality education for all students. PMID- 27405194 TI - A Nursing Workforce Diversity Project: Strategies for Recruitment, Retention, Graduation, and NCLEX-RN Success. AB - AIM: The purpose of this article is to describe a collaborative project designed to recruit and retain students from underrepresented minorities and disadvantaged backgrounds into nursing education. BACKGROUND: Ethnic minorities remain underrepresented in the nursing workforce in comparison to the general population. The numbers of minorities enrolled in nursing education programs are insufficient to meet the health care workforce diversity needs of the future. METHOD: High school students were provided with a preprofessional education program to prepare them for admission into a nursing program. Retention strategies were implemented for newly admitted and enrolled nursing education students. RESULTS: Twenty-one high school students enrolled in a nursing education program. The students enrolled in the nursing education program graduated and passed the licensure examination. CONCLUSION: Early recruitment and multiprong retention programs can be successful in diversifying the registered nurse workforce. PMID- 27405195 TI - Nursing Students' Attitudes Toward Lesbian, Gay, Bisexual, and Transgender Persons: An Integrative Review. AB - AIM: The aim of this study was to critically appraise and synthesize findings from studies on the attitudes of nursing students toward lesbian, gay, bisexual, and transgender (LGBT) persons. BACKGROUND: There is paucity of research to assess the attitudes of nursing students toward LGBT persons. METHOD: An electronic search was conducted using PubMed, Medline, Web of Science, EbscoHost, PsycInfo, and the Cumulative Index to Nursing and Allied Health Literature using medical subject headings terminologies. Search terms used included gay, lesbian, transgender, bisexual, LGBT, nursing students, baccalaureate nursing, undergraduate nursing, homophobia, homosexuality, sexual minority, attitudes, discrimination, and prejudice. RESULTS: Less than 50 percent of the studies (5 out of 12) suggested positively leaning attitudes of nursing students toward LGBT persons; six studies reported negative attitudes, and one study reported neutral attitudes. CONCLUSION: There are some indications that student attitudes may be moving toward positively leaning. Studies published before 2000 reported a preponderance of negative attitudes. PMID- 27405196 TI - Health Literacy Education in Baccalaureate Nursing Programs in the United States. AB - AIM: This study's aim was to determine the prevalence of health literacy education in nursing programs. Health literacy content and teaching strategies were also explored. BACKGROUND: Over 75 million Americans have low health literacy, a problem that can cause negative health outcomes. Knowledge about health literacy is important for nurses; yet, the extent to which the topic is included within nursing curricula is unknown. METHOD: An online survey was distributed to 150 nursing programs to obtain information about health literacy education in the curricula. RESULTS: Fifty-seven programs responded, with the majority reporting that health literacy is taught in their curricula. The impact of low health literacy and the importance of plain language were noted as common topics. CONCLUSION: The majority of participants reported inclusion of health literacy in their curricula using various teaching strategies. However, a low response rate prevents generalized conclusions. PMID- 27405197 TI - Students' Perspectives of Same-Day Clinical Assignments: A Qualitative Descriptive Study. AB - The clinical experience is essential to the nursing education process, but the process by which students are assigned patients has remained unchanged for decades. The purpose of this qualitative descriptive study was to determine the acceptability of a same-day clinical assignment process from the perspective of pre-licensure nursing students. Students' (n = 104) perceptions of the same-day clinical assignment process were collected via focus groups. Two themes emerged that may assist educators in implementing new methods for clinical assignments. PMID- 27405198 TI - Self-Regulated Learning: Examining the Baccalaureate Millennial Nursing Student's Approach. AB - Pre-licensure baccalaureate nursing programs are facing the demand to retain and graduate students with the skills needed for the complex health care environment. Nursing faculty are challenged to identify the best pedagogical methods for educating the current generation of students. The influence of student-centered approaches is documented in the literature. However, the effective use of these methods requires a collaborative partnership. The cognitive, self-regulated approaches used by millennial nursing students is not well understood. This article describes the findings of a study that examined the relationship between self-regulated approaches to learning, self-efficacy, independent study behaviors, and grade point average. PMID- 27405199 TI - Student QSEN Participation During an Adult Medical-Surgical Rotation. AB - With the six QSEN competencies woven throughout the baccalaureate nursing curriculum, which includes high-fidelity simulation, the aim of this research was to uncover deficits in QSEN-related clinical opportunities. Pre-licensure BSN nursing students enrolled in a sophomore-level medical-surgical rotation augmented with 25 percent simulation were observed directly, with time-on-task for each QSEN competency recorded and tabulated. The students were found to spend little time addressing several of the six competency areas in both clinical and simulation settings. Fully integrated classroom, simulation, and clinical experiences need to be considered in an effort to offer a full spectrum of QSEN based knowledge and skill theory and practice for pre-licensure nursing students. PMID- 27405200 TI - Answering Student Questions During Examinations: A Descriptive Study of Faculty Beliefs. AB - Examinations are used to evaluate individual student learning. Therefore, fair and consistent administration practices are essential. One issue associated with testing administration practices includes whether or not students should be allowed to ask questions during exams and how faculty should respond. Findings from this descriptive study indicate that faculty believe answering questions disrupts the testing environment, inhibits effective monitoring of the testing environment, and could provide unfair hints to students who ask questions. Yet, faculty permit students to ask questions to clarify unclear wording, to provide definitions, and to appear receptive to student needs. Recommendations for nursing education and research are provided. PMID- 27405201 TI - A Pilot Study to Explore Nurse Educator Workforce Issues. AB - As the demand for nurses continues to rise, the recruitment and retention of qualified nurse educators (NEs) is essential. The purpose of this descriptive study was to explore NE workforce issues using the Faculty Satisfaction Survey at a single nursing program. Respondents were somewhat to very satisfied with their job; however, they were less satisfied with salary/compensation and stated they would leave academia for higher wages. Satisfaction differences were noted between full-time and part-time NEs. Job motivators may be the key to recruitment and retention of NEs and a way to avoid a nursing shortage crisis. PMID- 27405202 TI - Using Innovative Teaching Strategies to Improve Outcomes in a Pharmacology Course. AB - It is often difficult to engage nursing students and keep their interest when teaching pharmacology. This article reports on an effective change from a lecture only approach to teaching with the use of games and case studies in a baccalaureate nursing education program. Improvements have been noted in standardized test scores and student evaluations, and students are more engaged in the learning process. Learning has been shifted from the instructor, as in the traditional classroom, and is now student focused. PMID- 27405203 TI - A Team Approach to Enhance Scholarship Among Honors Students in Nursing. AB - Honors programs within schools of nursing have the potential to enhance young nurses' interest in developing programs of research early in their careers and can thus contribute to the successful development of nursing knowledge. Such programs also provide opportunities to enhance knowledge and skill in leadership and teamwork at a critical time during the development of their professional nurse identity. This article presents the successful approach one organization took when revising its honors program to meet the current needs of students, society, and the profession. PMID- 27405205 TI - On the Horizon: Trends, Challenges, and Educational Technologies in Higher Education. PMID- 27405204 TI - Helping Students Process a Simulated Death Experience: Integration of an NLN ACE.S Evolving Case Study and the ELNEC Curriculum. AB - The nursing literature supports the need for end-of-life (EOL) education, but the ability to provide quality clinical experience in this area is limited by the availability of patients and nursing instructors' and preceptors' comfort and expertise in teaching EOL care. Clinical simulation allows faculty to provide the same quality EOL experience to all students. This article discusses an effective teaching strategy integrating End-of-Life Nursing Education Consortium core content with National League for Nursing ACE.S unfolding case studies, clinical simulation, and social media. PMID- 27405206 TI - [CURRENT IDEAS ON OBLIGATE AND FACULTATIVE RELATIONSHIPS BETWEEN MAN AND THE DIROFILARIASIS PATHOGEN DIROFILARIA (N.) REPENS]. AB - The ability of D. repens to complete its ontogenesis in man points to their obligate, rather than facultative rela- tionships. The fact that microfilariae are rarely found in human blood or are absent there may be associated with the removal of developing dirofilariae from humans in earlier than they achieve sexual maturity. Facultative ecological relationships to mosquitoes may be one of the reasons for limitation of human invasion cases. However, in long-standing microfilaremia in man (an obligate host), D.repens may take part in the epidemiological chain of dirofilariasis as a source of invasion. PMID- 27405207 TI - [INFECTION OF BLOOD-SUCKING MOSQUITOES (DIPTERA: CULICIDAE) WITH DIROFILARIAE (SPIRURIDA, ONCHOCERCIDAE) IN THE TULA REGION]. AB - Blood-sucking mosquitoes (n = 2277) collected in Tula and its Region in 2013-2014 were examined using a PCR assay for dirofilariae. A total of 12 species from 4 genera (Culiseta, Aedes, Ochlerotatus [foreign character] Culex) out of 18 found mosquito species were infected with Dirofilaria immitis and D. repens. The proportion of the infected mosquitoes was 2.5% (D. immitis, 1.5%; D.repens, 1%). According to preliminary data, the most efficient Dirofilaria vectors, in the Tula Region may be Ae. vexans, Ae. geniculatus, Och. cantans, and Cx. pipiens. PMID- 27405208 TI - [MALARIA IMPORTATION BY RUSSIA'S CITIZENS AND FOREIGNERS, INTO THE CITIES AND TOWNS OF THE RUSSIAN FEDERATION]. AB - A total of 436 malaria cases, including 12 from the CIS countries and 424 from far foreign countries (of Africa and Central and South-East Asia), were imported into the Russian Federation in 2010-2014. Most (96.6%) cases were notified in the urban areas of 52 administrative subjects of Russia. The largest number of the imported cases were seasonal workers (39.2%), tourists (31.3%), students and foreign postgraduate students (19.5%), and ship or aircraft crews (10%). During a short malaria transmission season (June to August), there were 150 cases of different types, out of them there were only 63 cases of tertian malaria (its pathogen is Plasmodium vivax, to which malaria mosquitoes of Russia's fauna are susceptible). The relatively small number of infection sources in the short transmission (June to August) season of malaria, its importation into low susceptibility large towns, and a small proportion of imported vivax malaria cases substantially reduce the risk of malaria in the highrisk areas of the country. PMID- 27405209 TI - [Experimental infection of rats with human Lamblia isolates is a model of long standing infection]. PMID- 27405211 TI - [Blood-sucking mosquitoes (family Culicidae) in the oak-groves of the Belgorod Region: Species-specific composition, phenological characteristics, and value in Dirofilaria transmission]. PMID- 27405210 TI - [THE PRESENT STATE OF EPIZOOTOLOGICAL MONITORING OF THE NATURAL FOCI OF INFECTIONS IN THE RUSSIAN FEDERATION]. AB - The facilities of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare play a leading role in epizootological monitoring. The specialists (zoologists and entomologists) of Hygiene and Epidemiology Centers do basic work in the subjects of the Russian Federation. The data obtained in the participation of different ministries and departments are used to analyze the results of monitoring. The latter is one of the important steps in the management of the epidemic, process in natural focal infections. In recent years, there has been an unjustified reduction in the volume of studies in the natural foci. This negatively affects the reliability of estimates and predictions of the epidemic activity of the natural foci of infections. Ensuring the national, security of the Russian Federation, epidemiological surveillance, and control of its natural foci requires staffing and appropriate professional training in the zoological and entomological subdivisions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare. PMID- 27405212 TI - [CIRCULATION OF DIROFILARIA REPENS (RAILLIET ET HENRY, 1911) IN THE ARID ZONE OF SOUTHERN RUSSIA]. AB - The prevalence of dirofilariasis was studied in dogs from the urban and rural areas in Southern Russia. The high prevalence of Dirofilaria repens infection were established among the dogs in the Republic of Kalmykia. The blood samples from 328 dogs were tested; D. repens infection was detected in 23.6 and 15.5% of the rural and urban dogs, respectively. The highest prevalence of D. repens infection was noted in of 4-6-year-old dogs. Dogs aged 0, 1-3, 4-6 7-9, and more 10 years were infected in 0, 26.3, 33.3, 29.4, and 28.5% of cases, respectively. PMID- 27405213 TI - [INSECTICIDE RESISTANCE IN MAJOR MALARIA VECTORS IN UZBEKISTAN]. AB - The resistance of Anopheles artemievi to DDT (26.7%) and propoxur (80.0%) was established in the kishlak of Chubat, Bulungursky District, Samarkand Viloyati and that in the kishlak of Rastguzar, Uichinsky District, Namangan Viloyati, was 45.0 and 22.5%, respectively. In the kishlak of Navruz, Kanlikulsky District, Republic of Karakalpakstan, there was reduced propoxur susceptibil- ity (90.0% An. superpictus death); in other human settle- ments, An. artemievi was susceptible--100% death in the use of the test insecticides. An. superpictus proved to be susceptive to 7 test insecticides (other than propoxur). In Uzbekistan, the resistance of An. artemievi was noted only in a small area. Among the major malaria vectors, An. superpictus remained susceptible to pyrethroid insec- ticides. PMID- 27405214 TI - [The anthelmintic nadinate (MCT-02) obtained by a new procedure and its antihymenolepic activity]. PMID- 27405215 TI - [Effect of the anthelmintic nadinate on rat serum hematological and biochemical parameters in the subchronic experiment]. PMID- 27405216 TI - [EXTERNAL QUALITY ASSESSMENT FOR THE LABORATORY IDENTIFICATION OF THE PATHOGENS OF PARASITIC DISEASES AS AN ELEMENT FOR IMPROVING THE POSTGRADUATE TRAINING OF SPECIALISTS]. AB - Within the framework of the Federal External Quality Assessment (EQA) System and in the context of postgraduate training improvement for health workers in 2010 2014, specialists from the laboratories of the therapeutic-prophylactic organizations and institutions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare were examined for their professional competence in microscopically identifying the pathogens of parasitic diseases in feces. The virtual remote educational computer technology tools that included different combinations of 16 helminthic species, 5 intestinal protozoan species, and a number of artefacts, were used. The specialists from 984 laboratories of multidisciplinary therapeutic-prophylactic organizations and hygiene and epidemiology centers in all Federal Districts of the Russian Federation were covered. A total of 8245 replies were analyzed. The detection rate for helminths was 64.0%, including those by a taxonomic group (nematodes, 65.0%; cestodes, 72.0%; trematodes, 55.1%). There was a dynamic decrease in the above indicators. There were low detection rates for trematodes parasitizing the small intestine (Metagonimus, 10.2%; Nanophyetus, 26.2%) and hepatobiliary organs (Fasciola, 59.6%; Clonorchis, 34.9%). The similar trend was seen in the detection rates for the pathogens of geohelminthisms (ascariasis, trichocephaliasis, etc.) and contagious helminthisms (enterobiasis, hymenolepiasis). The level of competence in detecting and identifying intestinal protozoa was much lower than the similar rates for helminthism pathogens. EQA for the laboratory diagnosis of the pathogens of parasitic diseases, by using the virtual tools is a leading element of the postgraduate training system for laboratory specialists. The results of EQA for the laboratory diagnosis of the pathogens of parasitic diseases are a basic material for the development, and improvement of training modernization programs, by applying a modular approach. PMID- 27405217 TI - [The psychological and pedagogical tasks for optimizing the training of health workers in the specialty of Parasitology]. PMID- 27405218 TI - [ANTHELMINTIC SUBSTANCES: MAIN CLASSES, PROBLEMS, TRENDS IN DEVELOPMENT AND PROSPECTS]. AB - The review chronologically considers the main classes of the currently available anthelminthic substances: early anthelmintic compounds, benzimidazoles, imidazolthiazoles, tetrahydropyrimidines, avermectins and milbemycins, and salicylanilides. Great attention is paid to novel substances (emodepside, monepantel, derquantel, tribendimidine) and promising developments. Some aspects of the molecular mechanisms of action of anthelmintics, their resistance, and alternative dehelmintization methods are discussed. PMID- 27405219 TI - [THE CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF MALARIA CONCURRENT WITH OTHER INFECTIONS AND INVASIONS]. AB - The present review considers malaria infection concurrent with different species of helminths, bacterial and viral infections, as well as mixed malaria pathogens in the subtropical and tropical countries of the world, causing the clinical picture and epidemiological situation to be different. Malaria co-infections with different pathogenic micro-organisms, such as HIV, tuberculosis, viral hepatitides, and others, affect almost one third of the planet's population. It is known that people who are at risk for malaria may be also at risk for other parasitic and infectious diseases, most commonly helminthisms. PMID- 27405220 TI - [Malaria elimination progress in the countries of the World Organization of Health European Region]. PMID- 27405221 TI - Yes! There are resilient generalizations (or "laws") in ecology. AB - ABSTRACT It is often argued that ecological communities admit of no useful generalizations or "laws" because these systems are especially prone to contingent historical events. Detractors respond that this argument assumes an overly stringent definition of laws of nature. Under a more relaxed conception, it is argued that ecological laws emerge at the level of communities and elsewhere. A brief review of this debate reveals an issue with deep philosophical roots that is unlikely to be resolved by a better understanding of generalizations in ecology. We therefore propose a strategy for transforming the conceptual question about the nature of ecological laws into a set of empirically tractable hypotheses about the relative re- silience of ecological generalizations across three dimensions: taxonomy, habitat type, and scale. These hypotheses are tested using a survey of 240 meta-analyses in ecology. Our central finding is that generalizations in community ecology are just as prevalent and as resilient as those in population or ecosystem ecology. These findings should help to establish community ecology as a generality-seeking science as opposed to a science of case studies. It also supports the capacity for ecologists, working at any of the three levels, to inform matters of public policy. PMID- 27405222 TI - RESILIENCE TO DROUGHTS IN MAMMALS: A CONCEPTUAL FRAMEWORK FOR ESTIMATING VULNERABILITY OF A SINGLE SPECIES. AB - ABSTRACT The frequency and severity of droughts in certain areas is increasing as a consequence of climate change. The associated environmental challenges, including high temperatures, low food, and water availability, have affected, and will affect, many populations. Our aims are to review the behavioral, physiological, and morphological adaptations of mammals to arid environments, and to aid research- ers and nature conservationists about which traits they should study to assess whether or not their study species will be able to cope with droughts. We provide a suite of traits that should be considered when making predictions about species resilience to drought. We define and differentiate between general adaptations, specialized adaptations, and exaptations, and argue that specialized adaptations are of little interest in establishing how nondesert specialists will cope with droughts. Attention should be placed on general adaptations of semidesert species and assess whether these exist as exaptations in nondesert species. We conclude that phenotypic flexibility is the most important general adaptation that may promote species resilience. Thus, to assess whether a species will be able to cope with increasing aridity, it is important to establish the degree offlexibility of traits identified in semidesert species that confer afitness advantage under drying conditions. PMID- 27405223 TI - DO SYMPTOMS OF ILLNESS SERVE SIGNALING FUNCTIONS? (HINT: YES). AB - Symptoms of illness provide information about an organism's underlying state. This notion has inspired a burgeoning body of research on organisms' adaptations for detecting and changing behavior toward ill individuals. However, little attention has been paid to a likely outcome of these dynamics. Once an organism's fitness is affected by others' responses to symptoms of illness, natural selection can favor individuals who alter symptom expression to influence the behavior of others. That is, many symptoms may originate as cues, but will evolve into signals. In this paper, I develop the hypothesis that symptoms of illness serve signaling functions, and provide a comprehensive review of relevant evidence from diverse disciplines. I also develop novel empirical predictions generated by this hypothesis and discuss its implications for public health. Signaling provides an ultimate explanation for otherwise opaque aspects of symptom expression, such as why symptoms fluctuate in social contexts, and can exist without underlying pathology, and why individuals deliberately generate symptoms of illness. This analysis suggests that signaling theory is a major organizing framework for understanding symptom etiology. PMID- 27405224 TI - Patch testing in Iranian children with allergic contact dermatitis. AB - BACKGROUND: Allergic contact dermatitis is a common disorder in adults and children alike and appears to be on the increase. The purpose of this study was to determine the sensitization trends in Iranian children with contact dermatitis. METHODS: The result of 109 patch tests performed using the 24 allergens of the European Standard Series in patients below 18 years old from September 2007 to March 2009 were recorded and analyzed. The tests were evaluated at 48 and 72 h after performing. RESULTS: The study population consisted of 72 (66.1 %) females and 37 (33.9 %) males. Hands were the most commonly affected anatomic site. In the final evaluation of the tests on day three, 51 (46.8 %) individuals showed a positive reaction to at least one allergen. Females were significantly more likely to show a positive response to at least one allergen (p value = 0.031, odds ratio: 2.46). The most common allergens were nickel sulfate, cobalt, methylisothiazolinone, and colophony with 21 (19.3 %), 11 (10.1 %), 7 (6.4 %), and 6 (5.5 %) positive reactions, respectively. Contact allergy to nickel sulfate was more common in females than males (23.6 % vs. 10.8 %). There was no statistically significant relationship between personal or family history of atopy and a positive reaction to patch testing. The clinical and practical relevance were assessed for nickel and cobalt with a clinical current relevance in 11 (52.3 %) and 4 (36.4 %), respectively. CONCLUSIONS: Nickel sulfate, cobalt, methylisothiazolinone, and colophony are the most common allergens responsible for induction of allergic contact dermatitis in Iranian children and adolescents. Females tended to show more positive reactions to allergens. PMID- 27405225 TI - Design of TRUST, a non-interventional, multicenter, 3-year prospective study investigating an integrated patient management approach in patients with relapsing-remitting multiple sclerosis treated with natalizumab. AB - BACKGROUND: Natalizumab provides rapid and high-efficacy control of multiple sclerosis disease activity with long-term stabilization. However, the benefits of the drug are countered by a risk of developing progressive multifocal leukoencephalopathy in patients infected with the John Cunningham Virus. Close monitoring is required in patients with increased progressive multifocal leukoencephalopathy risk receiving natalizumab in the long-term for an optimal benefit-risk evaluation. Standardized high-quality monitoring procedures may provide a superior basis for individual benefit and risk evaluation and thus improve treatment decisions. The non-interventional study TRUST was designed to capture natalizumab effectiveness under real-life conditions and to examine alternate approaches for clinical assessments, magnetic resonance imaging monitoring and use of biomarkers for progressive multifocal leukoencephalopathy risk stratification. METHODS/DESIGN: TRUST is a non-interventional, multicenter, prospective cohort study conducted at approximately 200 German neurological centers. The study is intended to enroll 1260 relapsing-remitting multiple sclerosis patients with ongoing natalizumab therapy for at least 12 months. Patients will be followed for a period of 3 years, irrespective of treatment changes after study start. Data on clinical, subclinical and patient-centric outcomes will be documented in order to compare the effectiveness of continuous versus discontinued natalizumab treatment. Furthermore, the type and frequency of clinical, magnetic resonance imaging and biomarker assessments, reasons for continuation or discontinuation of therapy and the safety profile of natalizumab will be collected to explore the impact of a systematic patient management approach and its potential impact on patient outcome. Specifically, the role of biomarkers, the use of expert opinions, the impact of high-frequency magnetic resonance imaging assessment for early progressive multifocal leukoencephalopathy detection and the role of additional radiological and clinical expert advice will be explored. DISCUSSION: TRUST was initiated in spring 2014 and enrollment is anticipated to be completed by mid 2016. Annual interim analyses will deliver continuous information and transparency with regard to the patient cohorts and the completeness and quality of data as well as closely monitor any safety signals in the natalizumab-treated cohort. The study's results may provide insights into opportunities to improve the benefit-risk assessment in clinical practice and support treatment decisions. PMID- 27405226 TI - Handoffs, safety culture, and practices: evidence from the hospital survey on patient safety culture. AB - BACKGROUND: The context of the study is the Agency for Healthcare Research and Quality's Hospital Survey on Patient Safety Culture (HSOPSC). The purpose of the study is to analyze how different elements of patient safety culture are associated with clinical handoffs and perceptions of patient safety. METHODS: The study was performed with hierarchical multiple linear regression on data from the 2010 Survey. We examine the statistical relationships between perceptions of handoffs and transitions practices, patient safety culture, and patient safety. We statistically controlled for the systematic effects of hospital size, type, ownership, and staffing levels on perceptions of patient safety. RESULTS: The main findings were that the effective handoff of information, responsibility, and accountability were necessary to positive perceptions of patient safety. Feedback and communication about errors were positively related to the transfer of patient information; teamwork within units and the frequency of events reported were positively related to the transfer of personal responsibility during shift changes; and teamwork across units was positively related to the unit transfers of accountability for patients. CONCLUSIONS: In summary, staff views on the behavioral dimensions of handoffs influenced their perceptions of the hospital's level of patient safety. Given the known psychological links between perception, attitude, and behavior, a potential implication is that better patient safety can be achieved by a tight focus on improving handoffs through training and monitoring. PMID- 27405230 TI - CD34 Selection and EX Vivo Expansion of Haemopoietic Progenitor Cells: A Review of Laboratory Methodology. AB - The CD34 antigen is expressed on haemopoietic stem and progenitor cells. A number of strategies have been developed which allow the selection and purification of CD34(+) cells from bone marrow, peripheral blood, and umbilical cord blood. Transplantation studies have amply demonstrated that rapid and durable engraftment can be achieved following reinfusion of selected CD34(+) cells. More recently, techniques have become available which can produce extensive proliferation of haemopoietic progenitor cells in ex vivo culture systems. The most popular method involves a simple liquid suspension culture system supplemented with a range of cytokines. The degree of expansion and, indeed, the types of cells produced can be significantly influenced by culture conditions like the choice of cytokines, duration of culture, starting cell concentration, and type of culture vessel. Despite many laboratory investigations, there have been few clinical trials using ex vivo expanded cells. Although it has been shown that infusion of ex vivo cultured cells is well tolerated with no associated toxicity, there is no evidence to date that these culture systems sustain sufficient numbers of haemopoietic long-term repopulating cells to secure durable engraftment following myeloablative therapy. Clearly, the major goal is to define culture conditions which will produce true stem cell expansion. PMID- 27405227 TI - Interactions between Lactobacillus rhamnosus GG and oral micro-organisms in an in vitro biofilm model. AB - BACKGROUND: Probiotics have shown favourable properties in maintaining oral health. By interacting with oral microbial communities, these species could contribute to healthier microbial equilibrium. This study aimed to investigate in vitro the ability of probiotic Lactobacillus rhamnosus GG (L.GG) to integrate in oral biofilm and affect its species composition. Five oral strains, Streptococcus mutans, Streptococcus sanguinis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Candida albicans were involved. The group setup included 6 mono-species groups, 3 dual-species groups (L.GG + S. mutans/S. sanguinis/C. albicans), and 4 multi-species groups (4/5 species and 4/5 species + L.GG, 4 species were all the tested strains except S. mutans). Cell suspensions of six strains were pooled according to the group setup. Biofilms were grown on saliva-coated hydroxyapatite (HA) discs at 37 degrees C in anaerobic conditions for 64.5 h. Biofilm medium was added and refreshed at 0, 16.5, and 40.5 h. The pH of spent media was measured. Viable cells of the 16.5 h and 64.5 h biofilms were counted. 64.5 h biofilms were stained and scanned with confocal laser scanning microscopy. RESULTS: Our results showed that L.GG and S. mutans demonstrated stronger adhesion ability than the other strains to saliva-coated HA discs. L.GG, C. albicans, S. mutans and F. nucleatum, with poor ability to grow in mono species biofilms demonstrated better abilities of adhesion and reproduction in dual- and/or multi-species biofilms. L.GG slightly suppressed the growth of C. albicans in all groups, markedly weakened the growth of S. sanguinis and F. nucleatum in 4sp + L.GG group, and slightly reduced the adhesion of S. mutans in L.GG+ S. mutans group. CONCLUSIONS: To conclude, in this in vitro model L.GG successfully integrated in all oral biofilms, and reduced the counts of S. sanguinis and C. albicans and lowered the biofilm-forming ability of F. nucleatum, but only slightly reduced the adhesion of S. mutans. C. albicans significantly promoted the growth of L.GG. PMID- 27405228 TI - Anatomical cross-sectional area of the quadriceps femoris and sit-to-stand test score in middle-aged and elderly population: development of a predictive equation. AB - BACKGROUND: Although the sit-to-stand (STS) test score has been shown to relate to the strength and size of the quadriceps femoris (QF) for elderly population, it is unknown whether this relationship is influenced by a posture (i.e., the trunk being allowed to stoop or not) during the STS test. The present study investigated the relationship between STS test score and QF anatomical cross sectional area (ACSA) in the middle-aged and elderly population with regard to the difference in the posture during STS test, and aimed to develop an accurate predicting equation of the QF ACSA from the STS test score. METHODS: 105 males (40-81 years) and 113 females (41-79 years) participated in the present study, then the subjects were divided at random as validation and cross-validation groups. Mid-thigh QF ACSA was determined by magnetic resonance imaging. Subjects performed a 10-repeated STS as fast as possible in two conditions: (1) with the trunk being allowed to stoop during the sitting phases, and (2) kept upright throughout the test. A power index of the STS test score was calculated based on an equation obtained in a previous study using the time taken for each test condition, the thigh and shank lengths, and body mass. In the validation group (n = 109), a stepwise multiple linear regression analysis was performed to create a predictive model of the ACSA with sex, age, the STS time, and power for both conditions as independent variables. The formulated predictive equation was examined in the cross-validation group (n = 109). RESULTS: In the validation group, a stepwise regression analysis revealed that STS power with upright trunk condition, sex, and age but not with the stooping condition, were selected as variables to predict QF ACSA (R (2) = 0.64, P < 0.001). There was no systematic error for the relationship between predicted and measured values in the cross validation group. CONCLUSIONS: These results indicate that STS test score with upright trunk condition is one of the indices of QF muscle size of the middle aged and elderly population. The estimated predicting equation should be useful in clinical and practical settings for the health promotion. PMID- 27405231 TI - Assessment of Clonality and Its Relevance in Acute Myeloid Leukaemia and Bone Marrow Transplantation. AB - The study of clonality in females is a useful tool in assessing states of neoplastic cell expansion in myeloid malignancies and remission status after chemotherapy and bone marrow transplant. Various experimental techniques have been developed based on the Lyon Hypothesis of X chromosome inactivation in females. Specific enzymes are utilised to distinguish active from inactive X chromosomes, distinctive patterns of which are then visualised by Southern blotting or more recently PCR. A valuable contribution to the nature of myeloid malignancies has been gained by these means. PMID- 27405232 TI - Induction of Apoptosis in Human Leukaemia Cells is Differentially Regulated by Vitamin D Derivatives and Retinoids. AB - The ability of 1,25-dihydroxyvitamin D3 and two of its analogues, EB1089 and KH1060 to induce apoptosis in two leukaemia cell lines, HL-60 and U937 were examined. In addition, the effects of the retinoid 9-cis retinoic acid (9-cis RA) were assessed alone or in combination with the vitamin D compounds. In both the HL-60 and U937 cell lines none of the vitamin D derivatives alone were capable of inducing apoptosis, as assessed by flow cytometry and cell death ELISA techniques. In contrast, 9-cis RA induced apoptosis in HL-60 but not U937 cells. Co-treatment of HL-60 cells with the vitamin D compounds and 9-cis RA resulted in an enhanced induction of apoptosis, which was not observed with U937 cell co treatment. Western analysis of bcl-2 and bax protein levels revealed that combinations of the vitamin D and retinoid compounds decreased bcl-2 in HL-60 but not U937 cells, suggesting a change in the bcl-2/bax heterodimeric ratio in the former which would favour apoptosis. Further Western analyses were performed to examine the regulation of vitamin D receptor (VDR), retinoid X receptor (RXR) and retinoic acid receptor (RAR) following single or co-treatment with their respective ligands. Studies revealed that 9-cis RA alone down-regulated RXR, and diminished VDR and RAR protein levels in the presence of the vitamin D compounds in both cell lines. However, in HL-60 cells the vitamin D derivatives were capable of preventing the further down-regulation of RXR in the presence of the retinoid. These results demonstrate cell specific responses to the induction of apoptosis and regulation of apoptosis related gene products by vitamin D and retinoid compounds, highlighting complex signalling interactions between their receptors. PMID- 27405233 TI - Hematological Effects of Chernobyl In Belarus: Do They Really Exist Ten Years Later? AB - While analysing exposure of the lymphohemopoietic system of the population of Belarus to ionizing radiation as a consequence of the Chernobyl nuclear accident it should be stated that the separation of the effect of low level radiation from the whole set of other Chernobyl factors including the socio-psychological and environmental situation is not reliable as currently these factors cannot be quantified fully. Structural, metabolic or functional changes of blood cells registered in exposed people which are believed to be deterministic but which are not unidirectional, and are based sometimes on inappropriately controlled clinical observations, may be of significance for the evaluation of certain non hematological diseases, as the deviations of hematopoietic and immune cell behaviour patterns may influence natural defence mechanisms, the incidence of diseases and their clinical manifestations. The risk of non-deterministic effects of irradiation associated with the Chernobyl accident is too low now for leukemias to be statistically found but it could not be ruled out entirely in future assuming combined unfavourable action of all environmental factors. PMID- 27405234 TI - Coexistent Polycythemia Vera and Chronic Lymphocytic Leukemia: Down-Regulation of Myeloid Clone by the Lymphoid Clone? AB - Coexistence of polycythemia vera (PV) and chronic lymphocytic leukemia (CLL) is a rare association. The clinical course in all cases has been remarkably mild, thus suggesting suppression and/or control of each disease by the other. We have studied a patient who exhibited a typical feature of PV for 6 years. After 3 years of remission, induced by (32)P, a mild form of PV reappeared in association with B-CLL. In order to investigate the possible influence of CLL to the mild expression of PV, we have performed several in vitro colony assays and the tumor necrosis factor (TNF) assay. Colony formation by patient's bone marrow hematopoietic progenitor cells showed "spontaneous" BFU-E and CFU-E. In addition, patient's plasma selectively inhibited growth of normal BFU-E and CFU-E colony formation. TNF bioactivity, analysed during the course of the disease, was reduced. These findings suggested the existence of an inhibitor of erythropoiesis that could be involved in a down regulation of the myeloid clone by the lymphoid clone in this patient. PMID- 27405235 TI - Sclerosing Mediastinitis Masquerading As A Lymphoma. AB - Fibrosing retroperitoneal changes can mimic malignant tumours. The correlation with beta-blockers has long been known where practolol was the prototype agent. It is now possible to report supradiaphragmatic occurrence of a similar pathology and its link with later generation beta adrenergic receptor blocking drugs leading to a diagnosis of lymphoma. This rare association needs to be included in the differential diagnosis of mass lesions in both abdomen and chest. PMID- 27405236 TI - Macrophage Inflammatory Protein-1 Alpha: A Paradox? AB - Macrophage inflammatory protein - 1 alpha (MIP-1alpha) is an 8kD protein which tends to form aggregates and is a member of the C-X-C chemokine subfamily, being a pro-inflammatory agent and is chemotactic for lymphocytes. MIP-1alpha has been shown to inhibit haemopoietic progenitor cell proliferation in vivo and in vitro and to reduce haemopoietic stem cell loss with improved neutrophil recovery after radiotherapy or chemotherapeutic agents in vivo. PMID- 27405237 TI - Adhesion and Transendothelial Migration of Human Monocytes: Role of Cytokine (IL3, GM-CSF) Activated Endothelial Cells. AB - In this study we have investigated the effect of GM-CSF and IL3 on Human Umbilical Vein Endothelial Cells (HUVEC). We studied the adhesion properties of HUVEC for non stimulated human elutriated monocytes, as well as the transendothelial migration of these cells. We analysed the expression of adhesion molecules (VLA4/CDw49d, VCAM1/CD106, LFA1/CD11a, ICAM1/CD54, CD18, L selectin/CD62L, PeCAMl/CD31, ELAM1/CD62E) induced in monocyte adhesion and transmigration. Optimal conditions of HUVEC stimulation with IL3 and GM-CSF were obtained with 100 U/ml of each cytokine. IL3 and GM-CSF were found to induce HUVEC proliferation, more than twofold at day 7 of the culture compared to controls. HUVEC proliferation was not stimulated by IL1alpha, a slight inhibitory effect was observed at 250 and 500 U/ml. We showed that GM-CSF, IL3 and their combination mimic on activation like status that on which is expressed by an enhancement of adhesion and migration of non stimulated monocytes to and across cytokines activated HUVEC monolayers. After 6 hours activation with IL3 or GM CSF, more than 60% of the monocytes are adherent to HUVEC after a contact of 30 minutes (vs 30.8 +/- 4.6% for untreated control HUVEC). This percentage increased to 80% after a 7 days culture period in presence of the same cytokines (vs 40 +/- 5.1% for untreated control HUVEC). IL3 was very effective at inducing monocyte transendothelial migration. The potency of IL3 is seen to be 2 to 3 fold higher than GM-CSF in this system. GM-CSF and IL3 modulate on HUVEC the expression of adhesion molecules induced in monocyte adhesion and transendothelial migration processes. We showed that anti-ELAMl inhibit in part monocyte migration (8.5 +/- 3% vs 46.33 +/- 4.03% without MoAb; vs 5.1 +/- 2% with ICAM1, ELAM1 and VCAMI MoAbs). PMID- 27405238 TI - Controversies Around Vitamin B12 in Sweden. AB - Over a five-year period, 1991-1995, the vitamin B12 market in Sweden increased three-fold, from approximately 2 million U.S. dollars to approximately 6 million U.S. dollars. Most prescriptions, approximately 60%, originated from primary health care. The attitudes, values and knowledge of the family physicians/general practitioners were elucidated by a questionnaire study with visuo-analogue opinion scales, evaluating 24 basic statements on problems associated with the management of vitamin B12 deficiency. The questionnaire was sent to a representative sample of 506 family physicians/general practitioners. Response rate was 74%. Dropout analysis supported the view that responders provided a representative sample of Swedish FP/GPs. Analysis of the answers was compatible with the hypothesis that the mentioned increase in Swedish B12 market reflected increased awareness in primary health care about the biochemical, pathophysiological and social problems associated with vitamin B12 deficiency. PMID- 27405239 TI - Exhalation of 131I after radioiodine therapy: Dosimetric considerations based on measurements in exhaled air. AB - It is well known that a considerable amount of radioiodine is exhaled after radioiodine therapy (RIT) leading to unwanted radiation exposure through inhalation for non-involved persons. This study focuses on the amount of exhalation in the breath-out air of RIT-patients and the dosimetric consequences. Furthermore, the correlation between radioiodine uptake and exhalation was investigated. The radioiodine species were collected in a filter system and quantified over time by measurements with a scintillation counter. The dosimetric implications were then studied for different exposure scenarios. Of the activity administered to the patient, approximately 10-3% (50-110 ppm) is exhaled. The radioiodine inhalation taking place following exhalation in the vicinity yields doses of up to 500 MUSv (children, staying with the patient immediately after application and for the next 8 h). Three days after administration the doses are significantly reduced. This study lays emphasis on previous assumptions that exhalation depends on thyroid storage. Regardless of the type of thyroid disease, the predominant form exhaled is organic radioiodine. The amount of exhaled radioiodine is small but from the point of view of radiation protection, by no means negligible immediately after administration. Radiation doses received by incorporation of exhaled radioiodine can easily exceed 100 MUSv soon after administration of radioiodine. Three days after RIT the radioactivity can still be measured in the exhaled air but even at maximum, the annual doses lie far below 10 MUSv and are thus comparatively low. PMID- 27405240 TI - Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore formation process. AB - Owing to their pathogenical role and unique ability to exist both as soluble proteins and transmembrane complexes, pore-forming toxins (PFTs) have been a focus of microbiologists and structural biologists for decades. PFTs are generally secreted as water-soluble monomers and subsequently bind the membrane of target cells. Then, they assemble into circular oligomers, which undergo conformational changes that allow membrane insertion leading to pore formation and potentially cell death. Aerolysin, produced by the human pathogen Aeromonas hydrophila, is the founding member of a major PFT family found throughout all kingdoms of life. We report cryo-electron microscopy structures of three conformational intermediates and of the final aerolysin pore, jointly providing insight into the conformational changes that allow pore formation. Moreover, the structures reveal a protein fold consisting of two concentric beta-barrels, tightly kept together by hydrophobic interactions. This fold suggests a basis for the prion-like ultrastability of aerolysin pore and its stoichiometry. PMID- 27405241 TI - Innovatively Supporting Teachers' Implementation of School-Based Sex Education: Developing A Web-Based Coaching Intervention From Problem to Solution. AB - BACKGROUND: Full program implementation is crucial for effectiveness but is often overlooked or insufficiently considered during development of behavioral change interventions. For school-based health promotion programs, teachers are key players in program implementation, but teacher support in this phase is mostly limited to technical support and information. To ensure optimal implementation of the Dutch school-based sexual health program Long Live Love, a Web-based coaching website was developed to support teachers in completeness and fidelity of program implementation. OBJECTIVE: The aim of this paper is to provide insight into the process of systematic development of a Web-based coaching intervention to support teachers in their implementation of a school-based sexual health program. METHODS: The intervention mapping (IM) protocol was applied for the development of a theory- and evidence-based intervention. The IM process begins with (1) a needs assessment, followed by (2) the formulation of change objectives, (3) the selection of theory-based intervention methods and practical applications that take the parameters for effectiveness into consideration, (4) integration of practical applications into an organized program, (5) planning for adoption, implementation, and sustainability of the program, and finally, (6) generating an evaluation plan to measure program effectiveness. RESULTS: Teacher's implementation behavior was characterized by inconsistently selecting parts of the program and not delivering (all) lessons as intended by program developers. Teachers, however, did not perceive this behavior as problematic, revealing the discrepancy between teacher's actual and perceived need for support in delivering Long Live Love lessons with completeness and fidelity. Teachers did, however, acknowledge different difficulties they encountered which could potentially negatively influence the quality of implementation. With the IM protocol, this Web-based coaching intervention was developed based on a concept of unobtrusive coaching, by and for teachers, to bring about change in teachers' implementation behavior. CONCLUSIONS: This paper provides an example of a Web-based intervention to bring about behavioral change in a target group of intermediaries who lack intrinsic motivation for coaching and who's perceptions differ from their actual problematic behavior. The IM protocol is a useful tool for guiding the scientific development of interventions and making them compatible with the needs and preferences of the target group. PMID- 27405243 TI - First-principles analysis of the spectroscopic limited maximum efficiency of photovoltaic absorber layers for CuAu-like chalcogenides and silicon. AB - Chalcopyrite semiconductors are of considerable interest for application as absorber layers in thin-film photovoltaic cells. When growing films of these compounds, however, they are often found to contain CuAu-like domains, a metastable phase of chalcopyrite. It has been reported that for CuInS2, the presence of the CuAu-like phase improves the short circuit current of the chalcopyrite-based photovoltaic cell. We investigate the thermodynamic stability of both phases for a selected list of I-III-VI2 materials using a first principles density functional theory approach. For the CuIn-VI2 compounds, the difference in formation energy between the chalcopyrite and CuAu-like phase is found to be close to 2 meV per atom, indicating a high likelihood of the presence of CuAu-like domains. Next, we calculate the spectroscopic limited maximum efficiency (SLME) of the CuAu-like phase and compare the results with those of the corresponding chalcopyrite phase. We identify several candidates with a high efficiency, such as CuAu-like CuInS2, for which we obtain an SLME of 29% at a thickness of 500 nm. We observe that the SLME can have values above the Shockley Queisser (SQ) limit, and show that this can occur because the SQ limit assumes the absorptivity to be a step function, thus overestimating the radiative recombination in the detailed balance approach. This means that it is possible to find higher theoretical efficiencies within this framework simply by calculating the J-V characteristic with an absorption spectrum. Finally, we expand our SLME analysis to indirect band gap absorbers by studying silicon, and find that the SLME quickly overestimates the reverse saturation current of indirect band gap materials, drastically lowering their calculated efficiency. PMID- 27405242 TI - Understanding the Differential Selectivity of Arrestins toward the Phosphorylation State of the Receptor. AB - Proteins in the arrestin family exhibit a conserved structural fold that nevertheless allows for significant differences in their selectivity for G protein coupled receptors (GPCRs) and their phosphorylation states. To reveal the mechanism of activation that prepares arrestin for selective interaction with GPCRs, and to understand the basis for these differences, we used unbiased molecular dynamics simulations to compare the structural and dynamic properties of wild type Arr1 (Arr1-WT), Arr3 (Arr3-WT), and a constitutively active Arr1 mutant, Arr1-R175E, characterized by a perturbation of the phosphate recognition region called "polar core". We find that in our simulations the mutant evolves toward a conformation that resembles the known preactivated structures of an Arr1 splice-variant, and the structurally similar phosphopeptide-bound Arr2-WT, while this does not happen for Arr1-WT. Hence, we propose an activation allosteric mechanism connecting the perturbation of the polar core to a global conformational change, including the relative reorientation of N- and C-domains, and the emergence of electrostatic properties of putative binding surfaces. The underlying local structural changes are interpreted as markers of the evolution of an arrestin structure toward an active-like conformation. Similar activation related changes occur in Arr3-WT in the absence of any perturbation of the polar core, suggesting that this system could spontaneously visit preactivated states in solution. This hypothesis is proposed to explain the lower selectivity of Arr3 toward nonphosphorylated receptors. Moreover, by elucidating the allosteric mechanism underlying activation, we identify functionally critical regions on arrestin structure that can be targeted with drugs or chemical tools for functional modulation. PMID- 27405244 TI - Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling. AB - Rotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naive NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses. Here we demonstrate bystander lymphocyte activation in RRV-infected NOD mice, which showed pDC activation and strong upregulation of interferon-dependent gene expression, particularly within lymph nodes. The requirement for type I interferon signalling was analysed using NOD mice lacking a functional type I interferon receptor (NOD.IFNAR1(-/-) mice). Compared with NOD mice, NOD.IFNAR1(-/ ) mice showed 8-fold higher RRV titers in lymph nodes and 3-fold higher titers of total RRV antibody in serum. However, RRV-infected NOD.IFNAR1(-/-) mice exhibited delayed pDC and lymphocyte activation, no T helper 1 bias in RRV-specific antibodies and unaltered diabetes onset when compared with uninfected controls. Thus, the type I interferon signalling induced by RRV infection is required for bystander lymphocyte activation and accelerated type 1 diabetes onset in genetically susceptible mice. PMID- 27405246 TI - Effect of Molecular Interactions on Electron-Transfer and Antioxidant Activity of Bis(alkanol)selenides: A Radiation Chemical Study. AB - Understanding electron-transfer processes is crucial for developing organoselenium compounds as antioxidants and anti-inflammatory agents. To find new redox-active selenium antioxidants, we have investigated one-electron transfer reactions between hydroxyl ((.) OH) radical and three bis(alkanol)selenides (SeROH) of varying alkyl chain length, using nanosecond pulse radiolysis. (.) OH radical reacts with SeROH to form radical adduct, which is converted primarily into a dimer radical cation (>Se?Se<)(+) and alpha {bis(hydroxyl alkyl)}-selenomethine radical along with a minor quantity of an intramolecularly stabilized radical cation. Some of these radicals have been subsequently converted to their corresponding selenoxide, and formaldehyde. Estimated yield of these products showed alkyl chain length dependency and correlated well with their antioxidant ability. Quantum chemical calculations suggested that compounds that formed more stable (>Se?Se<)(+) , produced higher selenoxide and lower formaldehyde. Comparing these results with those for sulfur analogues confirmed for the first time the distinctive role of selenium in making such compounds better antioxidants. PMID- 27405247 TI - Efficacy, outcomes, and complication rates of different surgical and nonsurgical treatment modalities for recurrent/residual oropharyngeal carcinoma: A systematic review and meta-analysis. AB - BACKGROUND: Treatment of recurrent oropharyngeal cancer is widely thought to have poor outcomes. Justification for treatment, especially in advanced cases, can be difficult. METHODS: A systematic search of MEDLINE, Embase, and Cochrane databases was conducted. Included studies reported specific recurrent oropharyngeal cancer survival data. RESULTS: Twenty-two retrospective studies were included. Pooled 3-year overall survival (OS) was 26% (95% confidence interval [CI] = 22% to 29%; I squared = 40.7%; p = .057). Pooled 5-year OS was 23% (95% CI = 20% to 27%; I squared = 73.9%; p = .000). Surgical treatment was superior to radiation (5-year OS 26% vs 16%, respectively; p < .001). The 5-year OS improved over time: 18% in the pre-2000 cohort; 35% in the mixed pre-2000 and post-2000 group; and 51% in the post-2000 cohort (p < .001). CONCLUSION: Outcomes have improved considerably over the last 2 decades, resulting in approximately 50% overall 5-year survival. Human papillomavirus (HPV) status, patient selection, and improvements in care may explain this. (c) 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck, 2016 (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1855-1861, 2016. PMID- 27405248 TI - A patient with schizophrenia presenting with post-lobotomy catatonia treated with olanzapine: a case report. AB - A 79-year-old Japanese woman with schizophrenia was hospitalized because of idiopathic duodenal stenosis. Three days after discontinuing ingestion, including the administration of psychotropic drugs, the patient demonstrated incoherent behaviour and strong general muscle tension, and was unable to engage in conversation. Computed tomography indicated bilateral regions of low density in the frontal lobes, subsequent to which she was diagnosed with post-lobotomy catatonia. Administration of olanzapine (10 mg/day) improved the patient's condition within a short period. Previous studies have demonstrated an association between the dysfunction of frontal circuits and catatonia; therefore, the observed catatonic episode might relate to the disconnection of nerve fibres in the prefrontal lobes induced by her lobotomy. Olanzapine was likely effective in treating catatonia because of its reported efficacy in improving frontal lobe function. PMID- 27405249 TI - The impact of conservation-driven translocations on blood parasite prevalence in the Seychelles warbler. AB - Introduced populations often lose the parasites they carried in their native range, but little is known about which processes may cause parasite loss during host movement. Conservation-driven translocations could provide an opportunity to identify the mechanisms involved. Using 3,888 blood samples collected over 22 years, we investigated parasite prevalence in populations of Seychelles warblers (Acrocephalus sechellensis) after individuals were translocated from Cousin Island to four new islands (Aride, Cousine, Denis and Fregate). Only a single parasite (Haemoproteus nucleocondensus) was detected on Cousin (prevalence = 52%). This parasite persisted on Cousine (prevalence = 41%), but no infection was found in individuals hatched on Aride, Denis or Fregate. It is not known whether the parasite ever arrived on Aride, but it has not been detected there despite 20 years of post-translocation sampling. We confirmed that individuals translocated to Denis and Fregate were infected, with initial prevalence similar to Cousin. Over time, prevalence decreased on Denis and Fregate until the parasite was not found on Denis two years after translocation, and was approaching zero prevalence on Fregate. The loss (Denis) or decline (Fregate) of H. nucleocondensus, despite successful establishment of infected hosts, must be due to factors affecting parasite transmission on these islands. PMID- 27405251 TI - Effect of dialysis on fetal heart rate: is inpatient admission for fetal monitoring necessary? AB - OBJECTIVE: Pregnant patients receiving hemodialysis (HD) have long hospital stays for the purpose of electronic fetal monitoring (EFM) during HD, which allows for monitoring of fetal well-being. However, more frequent dialysis allows for smaller fluid shifts, preventing maternal hypotension. Our aim was to determine differences in rates of EFM abnormalities during HD versus non-stress testing (NST) off dialysis for gravid women with renal failure. METHODS: Retrospective cohort study over a 13-year period (2000-2013) identified five patients with renal failure in pregnancy. EFM tracings were reviewed during HD (cases) and routine inpatient NST off HD (controls). Standardized nomenclature was used to identify EFM abnormalities. The rate of abnormalities per hour of EFM was calculated. Kruskal-Wallis test was used and statistical significance was set at p < 0.05. RESULTS: There were no significant differences in late decelerations (p = 0.2) between cases and controls. Significantly fewer variable decelerations (p = 0.01) and contractions (p <=0.001) were noted during dialysis compared to controls. Significantly more prolonged decelerations (p = 0.02) were noted during HD compared to controls. CONCLUSION: There may be no fetal benefit of EFM during HD for gravid women with renal disease attributed to hypertensive and diabetic nephropathy. There may be cost savings by shifting HD to the outpatient setting. PMID- 27405250 TI - Interaction between irbesartan, peroxisome proliferator-activated receptor (PPAR gamma), and adiponectin in the regulation of blood pressure and renal function in spontaneously hypertensive rats. AB - Adiponectin exerts vasodilatory effects. Irbesartan, an angiotensin receptor blocker, possesses partial peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist activity and increases circulating adiponectin. This study explored the effect of irbesartan alone and in combination with adiponectin on blood pressure, renal hemodynamic excretory function, and vasoactive responses to angiotensin II and adrenergic agonists in spontaneously hypertensive rat (SHR). Irbesartan was given orally (30 mg/kg/day) for 28 days and adiponectin intraperitoneally (2.5 MUg/kg/day) for last 7 days. Groups of SHR received either irbesartan or adiponectin or in combination. A group of Wistar Kyoto rats (WKY) served as controls. Metabolic data and plasma samples were taken on days 0, 21, and 28. In acute studies, the renal vasoconstrictor actions of angiotensin II (ANGII), noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) were determined. SHR control rats had a higher mean blood pressure than the WKY (132 +/- 7 vs. 98 +/- 2 mmHg), lower plasma and urinary adiponectin, creatinine clearance, urine flow rate and sodium excretion, and oxidative stress markers compared to WKY (all P < 0.05) which were progressively normalized by the individual drug treatments and to a greater extent by combined treatment. Responses to intrarenal administration of NA, PE, ME, and ANGII were larger in SHR (P < 0.05) than WKY by 20-25 %. Irbesartan enhanced (P < 0.05) responses to NA and PE, while adiponectin blunted responses to all vasoconstrictors (all P < 0.05). Combined treatment in SHR further decreased the renal vascular responses to ANGII. These findings suggest that an interactive relationship may exist between PPAR-gamma, alpha adrenoceptors, and ANGII in the renal vasculature of the SHR. PMID- 27405252 TI - Impact of Food Restriction on the Expression of the Adiponectin System and Genes in the Hypothalamic-Pituitary-Ovarian Axis of Pre-Pubertal Ewes. AB - Adiponectin, a cytokine secreted typically by adipocytes, has been implicated as a molecular switch between female reproduction and energy balance. The present study was undertaken to investigate the expression of adiponectin system and patterns of genes in the hypothalamic-pituitary-ovary (HPO) axis of food restricted pre-pubertal ewes. Eighteen 2-month-old female ewes were assigned to 3 groups after a pre-feeding ad libitum for 10 days (six in each group): the control group (C), the low-food-restricted group (LR) and the high-food restricted group (HR), which were fed with 100%, 70% and 50% of ad libitum food intake, respectively. The hypothalamus, pituitary, ovary and serum were collected after food restriction for 2 months. Results by ELISA showed that food restriction increased serum adiponectin concentrations. Quantitative real-time PCR showed that the gene transcriptions for adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) were enhanced in the hypothalamic-pituitary-ovarian (HPO) axis, while KISS-1/GPR-54 and gonadotropin-releasing hormone (GnRH) in the hypothalamus and luteinizing hormone beta-subunit (LHbeta) and follicle-stimulating hormone beta subunit (FSHbeta) in the pituitary were reduced after food restriction. Immunohistochemistry results demonstrated that AdipoR1 localized in the oocytes of follicles in the ovary. These results suggest that the alterations in the expression of adiponectin and its receptors in response to food restriction might negatively influence the HPO axis. PMID- 27405253 TI - Dual blockade of hepatitis C virus entry at a gatekeeper of hepatocytes: Not only a preventive, but also therapeutic target of claudin 1. PMID- 27405254 TI - Preface to DMR special edition "cytochrome P450: new horizons". PMID- 27405255 TI - Mechanically robust, chemically inert superhydrophobic charcoal surfaces. AB - We report a fast and cost-effective strategy towards the preparation of superhydrophobic composites where a double-sided adhesive tape is paved with charcoal particles. The composites are mechanically robust, and resistant to strong chemical agents. PMID- 27405256 TI - A localized and propagating SPR, and molecular imprinting based fiber-optic ascorbic acid sensor using an in situ polymerized polyaniline-Ag nanocomposite. AB - We report a successful approach for the fabrication and characterization of a fiber-optic sensor for ascorbic acid (AA) detection, using a molecularly imprinted polyaniline-Ag (PANI-Ag) nanocomposite layer based on the combined phenomena of surface plasmon resonance (SPR) and localized SPR (LSPR). The PANI Ag nanocomposite is synthesized by an in situ polymerization process and AA imprints are prepared on the polymeric composite. The confirmation of the PANI-Ag nanocomposite and AA imprinting is performed using various characterization methods such as x-ray diffraction (XRD), UV-vis, Fourier transform infrared spectroscopy and scanning electron microscopy. From XRD, the size of Ag nanoparticles is analyzed. The absorbance spectra are recorded for samples of different concentrations of AA around the sensing region of the probe. An increase in peak absorbance wavelength with the increase in AA concentration is observed with a linear response for the concentration range from 10(-8) M to 10( 6) M. The sensor possesses a high sensitivity of 45.1 nm log(-1) M near an AA concentration of 10(-8) M. The limit of detection (LOD) and limit of quantification of the sensor are found to be 7.383 * 10(-11) M and 4.16 * 10(-10) M, respectively. The LOD of the sensor is compared to studies reported in the literature and is found to be the lowest. The sensor possesses several other advantages such as cost effectiveness, selectivity, and low response time (<5 s), along with abilities of remote sensing and online monitoring. PMID- 27405258 TI - A commentary on Liang et al.'s paper with regard to emerging views of memory assessment in Alzheimer's disease. PMID- 27405259 TI - A matter of hand: Causal links between hand dominance, structural organization of fronto-parietal attention networks, and variability in behavioural responses to transcranial magnetic stimulation. AB - Considerable evidence suggests that, on a group level, human visuospatial attention is asymmetrically organized, with a right-hemispheric dominance. The asymmetrical organization of the superior longitudinal fasciculus (SLF) has been shown to account for the right-hemispheric dominance in visual attention. However, such account is by no means universal, and large individual differences in asymmetrical performance on visuospatial tasks have been reported. Furthermore, the variability in the SLF lateralization has been shown to correlate with behavioural asymmetries. Continuous theta burst stimulation (cTBS) enables to temporarily interfere with cortical activity. cTBS applied over the posterior parietal cortex (PPC) has been previously used to systematically study attentional asymmetries. Interestingly, large individual differences in the effectiveness of stimulation have been reported. In accordance with earlier both animal and human studies, one possible cause underlying these striking individual differences might lie in the structural organization of frontoparietal pathways subserving visuospatial attention. Thus, the current study employed diffusion tractography to examine the relationship between the variability in the structural organization of the SLF and the individual differences in attentional shifts induced by a modified cTBS (cTBSmod; triplets of pulses at 30 Hz, repeated at 6 Hz) applied over the IPS, as measured by a line bisection task. Consistent with previous studies, on a group level, cTBSmod applied over the right intraparietal sulcus (IPS) triggered a rightward bisection bias shift, and there were no significant effects of cTBSmod applied over the left IPS. However, further analyses demonstrated that both handedness and structural variability (as assessed based on hindrance modulated orientational anisotropy) within the middle and the ventral branches of the SLF predicted individual differences in the cTBSmod-induced attentional shifts. Our study thus suggests that the effects of cTBSmod over the IPS may depend on intra-hemispheric interactions between cortical loci controlling visual attention. To conclude, our findings provide converging evidence for the notion put forward previously that inter-individual variability in the structural organization of intra-hemispheric frontoparietal connections has important implications for the functional models of human visual attention. Moreover, we hypothesize that this may also be relevant for the understanding of attentional disorders and their rehabilitation. PMID- 27405260 TI - Paranasal sinuses: A problematic proxy for climate adaptation in Neanderthals. PMID- 27405257 TI - Epigenetic control of adult stem cell function. AB - Mammalian embryonic development is a tightly regulated process that, from a single zygote, produces a large number of cell types with hugely divergent functions. Distinct cellular differentiation programmes are facilitated by tight transcriptional and epigenetic regulation. However, the contribution of epigenetic regulation to tissue homeostasis after the completion of development is less well understood. In this Review, we explore the effects of epigenetic dysregulation on adult stem cell function. We conclude that, depending on the tissue type and the epigenetic regulator affected, the consequences range from negligible to stem cell malfunction and disruption of tissue homeostasis, which may predispose to diseases such as cancer. PMID- 27405261 TI - Enrichment of thermosensitive chitosan hydrogels with glycerol and alkaline phosphatase for bone tissue engineering applications. AB - Thermosensitive injectable chitosan hydrogels can be formed by neutralization of acidic chitosan solutions with sodium betaglycerophosphate (Na-beta-GP) coupled with increasing temperature to body temperature. Such hydrogels have been considered for applications in bone regeneration. In this study, chitosan hydrogels were enriched with glycerol and the enzyme alkaline phosphatase (ALP) with a view to improving their suitability as materials for bone tissue engineering. Mineral formation was confirmed by infrared spectroscopy (FTIR) and increases in the mass fraction of the hydrogel not consisting of water. Incorporation of ALP in hydrogels followed by incubation in a solution containing calcium ions and glycerophosphate, a substrate for ALP, led to formation of calcium phosphate within the hydrogel. MG-63 osteoblast-like cells were cultivated in eluates from hydrogels containing ALP and without ALP at different dilutions and directly on the hydrogel samples. Hydrogels containing ALP exhibited superior cytocompatibility to ALP-free hydrogels. These results pave the way for the use of glycerol- and ALP-enriched hydrogels in bone regeneration. PMID- 27405262 TI - Self-Inflicted Nailgun-Induced Penetrating Penile Injury: Case Report and Discussion. AB - Penetrating penile injuries occur mostly in industrial/work accidents, automobile accidents, or as a result of sexual curiosity and attempts at self expression/mutilation. In this case report, the authors describe an accidental nailgun injury to the penis of a 46-year-old man. We discuss the management of such injuries in the emergency department, including the utility of a dorsal penile block for regional anesthesia. Although exceptionally rare, familiarity with penetrating lower urinary tract injuries may reduce their long-term repercussions on genitourinary and sexual health. PMID- 27405264 TI - Characterization of the temperature rise in a single cell during photoacoustic tomography at the nanoscale. AB - We are developing a label-free nanoscale photoacoustic tomography (nPAT) for imaging a single living cell. nPAT uses a laser-induced acoustic pulse to generate a nanometer-scale image. The primary motivation behind this imaging technique is the imaging of biological cells in the context of diagnosis without fluorescent tagging. During this procedure, thermal damage due to the laser pulse is a potential risk that may damage the cells. A physical model is built to estimate the temperature rise and thermal relaxation during the imaging procedure. Through simulations using finite element methods, two lasers (532 nm at 5 ps pulse duration and 830 nm at 0.2 ps pulse duration) were simulated for imaging red blood cells (RBCs). We demonstrate that a single 5-ps pulse laser with a 400-Hz repetition rate will generate a steady state temperature rise of less than a Kelvin on the surface of the RBCs. All the simulation results show that there is no significant temperature rise in an RBC in either single pulse or multiple pulse illumination with a 532-nm laser with 219 W fluence. Therefore, our simulation results demonstrate the thermal safety of an nPAT system. The photoacoustic signal generated by this laser is on the order of 2.5 kPa, so it should still be large enough to generate high-resolution images with nPAT. Frequency analysis of this signal shows a peak at 1.47 GHz, with frequencies as high as 3.5 GHz still being present in the spectrum. We believe that nPAT will open an avenue for disease diagnosis and cell biology studies at the nanometer level. PMID- 27405265 TI - Continuous-terahertz-wave molecular imaging system for biomedical applications. AB - Molecular imaging techniques are becoming increasingly important in biomedical research and potentially in clinical practice. We present a continuous-terahertz (THz)-wave molecular imaging system for biomedical applications, in which an infrared (IR) laser is integrated into a 0.2-THz reflection-mode continuous-THz wave imaging system to induce surface plasmon polaritons on the nanoparticles and further improve the intensity of the reflected signal from the water around the nanoparticles. A strong and rapid increment of the reflected THz signal in the nanoparticle solution upon the IR laser irradiation is demonstrated, using either gold or silver nanoparticles. This low-cost, simple, and stable continuous-THz wave molecular imaging system is suitable for miniaturization and practical imaging applications; in particular, it shows great promise for cancer diagnosis and nanoparticle drug-delivery monitoring. PMID- 27405266 TI - Magnetic domain imaging of nano-magnetic films using magnetic force microscopy with polar and longitudinally magnetized tips. AB - Perpendicular or parallel magnetic fields are used to magnetize the tips used in magnetic force microscopy (MFM). In this process, perpendicular or parallel magnetic dipole moments are produced on the tip plane, thus leading to the formation of polar magnetized tips (PM-tips) or longitudinally magnetized tips (LM-tips), respectively. The resolution of an MFM image of a magneto-optic disk is used for calibration of these tips, and the saturated magnetic fields of the PM- and LM-tips are found to be 2720 Oe and 680 Oe, respectively. Because both tips can simultaneously magnetize the sample during the scanning process when measuring a Co thin film, clear MFM images are captured, which enable the identification of magnetizable regions and the distribution of the magnetic domains on the sample surface. These results will be useful for improving the manufacturing processes required for soft nano-magnetic film production. PMID- 27405267 TI - The combined effect of water status and crop level on Tempranillo wine volatiles. AB - BACKGROUND: The effect of water status and crop level on the volatile composition of Tempranillo wine was investigated over two growing seasons (2010-2011) in Extremadura (Spain). Three water status treatments (T0, Rainfed control; T1, Early regulated deficit irrigation; T2, Late regulated deficit irrigation) were combined with two crop levels treatments (TH, cluster thinning; C, control). RESULTS: Crop level treatment had a higher effect on individual volatiles analyzed in Tempranillo wine than water status. The combinations of water status and crop level treatments showed effects on all families of compounds with the exception of acetates and volatile fatty acids. Alcohols, C6 compounds and phenol volatiles produced the highest concentrations at the lower level of available water and when cluster thinning was applied (T0-TH). However, ethyl ester and lactones showed higher concentrations in regulated deficit irrigation (T1 and T2) and when cluster thinning was not applied. CONCLUSION: The combined effect of rainfed and cluster-thinning treatments (T0-TH) increased the majority of individual aromatic compounds quantified in Tempranillo wines and also showed the highest total odor activity value. (c) 2016 Society of Chemical Industry. PMID- 27405268 TI - A general framework for the Quantum Zeno and anti-Zeno effects. AB - Repeated measurements can slow down (the quantum Zeno effect) or speed up (the quantum anti-Zeno effect) the temporal evolution of a quantum system. In this paper, a general treatment of the quantum Zeno and anti-Zeno effects is presented which is valid for an arbitrary system-environment model in the weak system environment coupling regime. It is shown that the effective lifetime of a quantum state that is subjected to repeated projective measurements depends on the overlap of the spectral density of the environment and a generalized 'filter function'. This filter function depends on the system-environment Hamiltonian, the state of the environment, and the measurement being performed. Our general framework is then used to study explicitly the Zeno to anti-Zeno crossover behaviour for the spin-boson model where a single two-level system is coupled to a bosonic environment. It is possible to not only reproduce results for the usual population decay case as well as for the pure dephasing model, but to also study the regime where both decay and dephasing take place. These results are then extended to many two-level systems coupled collectively to the bosonic environment to further illustrate the importance of the correct evaluation of the effective decay rate. PMID- 27405269 TI - Extracellular mercury sequestration by exopolymeric substances produced by Yarrowia spp.: Thermodynamics, equilibria, and kinetics studies. AB - Exopolymeric substances (EPS) produced by highly mercury-resistant strains of the yeast Yarrowia spp. (Idd1 and Idd2) were isolated and studied for their mercury binding potential. Excellent yield (approximately 0.3 g EPS per gram biomass) of soluble EPS in medium with 3% glucose was observed in the Yarrowia cultures 7 day post-inoculation. A gram dry weight of the EPS consists mainly of carbohydrates (0.4 g), protein (0.3-0.4 g), uronic acid (0.02 g), and nucleic acids (0.002 g). Mercury interactions with the biopolymer were measured as uptake kinetics from a simulated aquatic system and modelled with thermodynamics and calculated mass action equilibria. The EPS forms a complex with Hg2+ in water with small activation energy (<=2 kJ mol-1), achieving about 30 mg Hg2+ adsorption per gram dry weight of EPS. The adsorption models confirmed complexation of Hg2+ by the EPS via heterogeneous multilayer adsorption that obey second-order kinetics at constant rate of 4.0 and 8.1 mg g-1 min-1. The EPS used chemisorption as rate limiting step that controls the uptake of Hg2+ from aquatic systems during micro precipitation as bio-removal strategy. The EPS are promising biotechnological tools to design bioreactors for treatment of mercury-rich industrial wastewater. PMID- 27405270 TI - Novel perfusion-decellularized method to prepare decellularized ureters for ureteral tissue-engineered repair. AB - As the endoscopic technique is widely used in the diagnosis and treatment of diseases, the incidence of ureteral injuries increases annually. The classical surgical therapies are not always satisfactory. With the constant development of the tissue engineering technology in the field of urinary reconstruction, the ureteral reconstruction has become possible technology. In this study, a novel perfusion-decellularized protocol, which combined a perfusion system with the commonly used physical and chemical methods, was used to prepare the decellularized ureters for ureteral reconstruction and the urinary tract-derived cells (UDCs) were seeded on the surface of the perfusion-decellularized ureters (PDUs) in order to observe the cells survival, adhesion, proliferation and distribution. The data of H&E staining, DAPI staining, and the agarose gel electrophoresis demonstrated that the cellular components of PDUs were removed, and the decellularized time was shorter than previous study. In addition, compared with the native ureters, the DNA content of the PDUs was significantly decreased just two percent residue (P<0.05). Scanning electron microscopy, collagen and glycosaminoglycan content assay showed that the three-dimensional (3D) ultrastructure and the compositions of the extracellular matrix (ECM) of PDUs were well preserved. When the UDCs were seeded onto the PDUs, the UDCs formed multilayer structure on the surface of the PDUs, infiltrated into the deep layer of the decellularized ureters and then formed laminated structure. In conclusion, the decellularized ureters prepared by the novel perfusion decellularized method may be the potential surrogate for ureteral tissue engineered repair. PMID- 27405271 TI - Styrene production from a biomass-derived carbon source using a coculture system of phenylalanine ammonia lyase and phenylacrylic acid decarboxylase-expressing Streptomyces lividans transformants. AB - To produce styrene from a biomass-derived carbon source, Streptomyces lividans was adopted as a host strain. The gene encoding ferulic acid decarboxylase from Saccharomyces cerevisiae (FDC1) was introduced into S. lividans, and the resulting S. lividans transformant successfully expressed FDC1 and converted trans-cinnamic acid (CA) to styrene. A key factor in styrene production using microbes is the recovery of volatile styrene. In the present study, we selected polystyrene resin beads XRD-4 as the absorbent agent to recover styrene produced using S. lividans transformants, which enabled recovery of styrene from the culture broth. For styrene production from biomass-derived carbon sources, S. lividans/FDC1 was cultured together with S. lividans/p-encP, which we previously reported as a CA-producing S. lividans strain. This coculture system combined with the recovery of styrene using XAD-4 allowed the production of styrene from glucose, cellobiose, or xylo-oligosaccharide, respectively. PMID- 27405272 TI - Tetracycline-incorporated polymer nanofibers as a potential dental implant surface modifier. AB - This study investigated the antimicrobial and osteogenic properties of titanium (Ti) disks superficially modified with tetracycline (TCH)-incorporated polymer nanofibers. The experiments were carried out in two phases. The first phase dealt with the synthesis and characterization (i.e., morphology, mechanical strength, drug release, antimicrobial activity, and cytocompatibility) of TCH-incorporated fibers. The second phase was dedicated to evaluating both the antimicrobial and murine-derived osteoprecursor cell (MC3T3-E1) response of Ti-modified with TCH incorporated fibers. TCH was successfully incorporated into the submicron-sized and cytocompatible fibers. All TCH-incorporated mats presented significant antimicrobial activity against periodontal pathogens. The antimicrobial potential of the TCH-incorporated fibers-modified Ti was influenced by both the TCH concentration and bacteria tested. At days 5 and 7, a significant increase in MC3T3-E1 cell number was observed for TCH-incorporated nanofibers-modified Ti disks when compared to that of TCH-free nanofibers-modified Ti-disks and bare Ti. A significant increase in alkaline phosphatase (ALP) levels on the Ti disks modified with TCH-incorporated nanofiber on days 7 and 14 was seen, suggesting that the proposed surface promotes early osteogenic differentiation. Collectively, the data suggest that TCH-incorporated nanofibers could function as an antimicrobial surface modifier and osteogenic inducer for Ti dental implants. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2085-2092, 2017. PMID- 27405274 TI - Background radiation and childhood leukemia: A nationwide register-based case control study. AB - High doses of ionizing radiation are an established cause of childhood leukemia. However, substantial uncertainty remains about the effect of low doses of radiation, including background radiation and potential differences between genetic subgroups of leukemia have rarely been explored. We investigated the effect of the background gamma radiation on childhood leukemia using a nationwide register-based case-control study. For each of the 1,093 cases, three age- and gender matched controls were selected (N = 3,279). Conditional logistic regression analyses were adjusted for confounding by Down syndrome, birth weight (large for gestational age), and maternal smoking. Complete residential histories and previously collected survey data of the background gamma radiation in Finland were used to assess the exposure of the study subjects to indoor and outdoor gamma radiation. Overall, background gamma radiation showed a non-significant association with the OR of childhood leukemia (OR 1.01, 95% CI 0.97, 1.05 for 10 nSv/h increase in average equivalent dose rate to red bone marrow). In subgroup analyses, age group 2-<7 years displayed a larger effect (OR 1.27, 95% CI 1.01, 1.60 for 1 mSv increase in equivalent cumulative dose to red bone marrow). Suggestive difference in OR by genetic subtype was found. Our results provide further support to the notion that low doses of ionizing radiation increase the risk for childhood leukemia, particularly at age 2-<7 years. Our findings suggest a larger effect of radiation on leukemia with high hyperpdiploidy than other subgroups, but this result requires further confirmation. PMID- 27405273 TI - Clathrin regulates lymphocyte migration by driving actin accumulation at the cellular leading edge. AB - Lymphocyte migration, which is essential for effective immune responses, belongs to the so-called amoeboid migration. The lymphocyte migration is up to 100 times faster than between mesenchymal and epithelial cell types. Migrating lymphocytes are highly polarized in three well-defined structural and functional zones: uropod, medial zone, and leading edge (LE). The actiomyosin-dependent driving force moves forward the uropod, whereas massive actin rearrangements protruding the cell membrane are observed at the LE. These actin rearrangements resemble those observed at the immunological synapse driven by clathrin, a protein normally involved in endocytic processes. Here, we used cell lines as well as primary lymphocytes to demonstrate that clathrin and clathrin adaptors colocalize with actin at the LE of migrating lymphocytes, but not in other cellular zones that accumulate both clathrin and actin. Moreover, clathrin and clathrin adaptors, including Hrs, the clathrin adaptor for multivesicular bodies, drive local actin accumulation at the LE. Clathrin recruitment at the LE resulted necessary for a complete cell polarization and further lymphocyte migration in both 2D and 3D migration models. Therefore, clathrin, including the clathrin population associated to internal vesicles, controls lymphocyte migration by regulating actin rearrangements occurring at the LE. PMID- 27405275 TI - Evaluation of short synthetic antimicrobial peptides for treatment of drug resistant and intracellular Staphylococcus aureus. AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue beta-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections. PMID- 27405278 TI - Observation of antisite domain boundaries in Cu2ZnSnS4 by atomic-resolution transmission electron microscopy. AB - Atomic resolution transmission electron microscopy has been used to examine antisite defects in Cu2ZnSnS4 (CZTS) kesterite crystals grown by a hot injection method. High angle annular dark field (HAADF) imaging at sub-0.1 nm resolution, and lower magnification dark field imaging using reflections sensitive to cation ordering, are used to reveal antisite domain boundaries (ADBs). These boundaries, typically 5-20 nm apart, and extending distances of 100 nm or more into the crystals, lie on a variety of planes and have displacements of the type 1/2[110] or 1/4[201], which translate Sn, Cu and Zn cations into antisite positions. It is shown that some ADBs describe a change in the local stoichiometry by removing planes of S and either Cu or Zn atoms, implying that these boundaries can be electrically charged. The observations also showed a marked increase in cation disorder in regions within 1-2 nm of the grain surfaces suggesting that growth of the ordered crystal takes place at the interface with a disordered shell. It is estimated that the ADBs contribute on average ~0.1 antisite defect pairs per unit cell. Although this is up to an order of magnitude less than the highest antisite defect densities reported, the presence of high densities of ADBs that may be charged suggests these defects may have a significant influence on the efficiency of CZTS solar cells. PMID- 27405276 TI - Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis. AB - Various pathophysiologic mechanisms leading to sickness behaviors have been proposed. For example, an inflammatory process in the hypothalamus has been implicated, but the signaling modalities that involve inflammatory mechanisms and neuronal circuit functions are ill-defined. Here, we show that toll-like receptor 2 (TLR2) activation by intracerebroventricular injection of its ligand, Pam3CSK4, triggered hypothalamic inflammation and activation of arcuate nucleus microglia, resulting in altered input organization and increased activity of proopiomelanocortin (POMC) neurons. These animals developed sickness behavior symptoms, including anorexia, hypoactivity, and hyperthermia. Antagonists of nuclear factor kappa B (NF-kappaB), cyclooxygenase pathway and melanocortin receptors 3/4 reversed the anorexia and body weight loss induced by TLR2 activation. These results unmask an important role of TLR2 in the development of sickness behaviors via stimulation of hypothalamic microglia to promote POMC neuronal activation in association with hypothalamic inflammation. PMID- 27405277 TI - Exploratory social network analysis and gene sequencing in people who inject drugs infected with hepatitis C virus. AB - Social networks facilitate the transmission of hepatitis C virus (HCV) in people who inject drugs (PWID). The aim of this study was to assess how certain network structural characteristics are related to HCV infections in PWID and to determine the most susceptible individuals for HCV transmission in a network of PWID. PWID (N = 80) from central China were recruited from a previous follow-up case-control study. Demographic and behavioural information was obtained from a computerized database for each group. HCV RNA was extracted from blood specimens. Sequences were used to construct a phylogenetic tree and to determine genetic distances. Socio-metric social links were established between participants. Network measures were calculated using UCINET. Three HCV genotypes were identified, covering five subtypes. The density of the social networks for the whole sample (N = 80), case group (n = 31) and control group (n = 49) was 0.038, 0.054 and 0.008, respectively. PWID infected with HCV were in frequent contact with others within their group. There were four pairs of nodes with genotypic distances of 0.000 that were identified and clustered in subtypes 6a and 1b; each subject pair was linked and found in one clique. Three of the five most active nodes were infected with HCV. These three nodes served as a bridge, contributing to the connection of other nodes. These findings identify susceptible individuals for HCV transmission in PWID based on their frequent contact with others in the network. These results provide data that could be used for modelling HCV transmission patterns and in public health policies. PMID- 27405279 TI - One-Dimensional ZnO/Gold Junction for Simultaneous and Versatile Multisensing Measurements. AB - The sensing capabilities of zinc oxide nano/micro-structures have been widely investigated and these structures are frequently used in the fabrication of cutting-edge sensors. However, to date, little attention has been paid to the multi-sensing abilities of this material. In this work, we present an efficient multisensor based on a single zinc oxide microwire/gold junction. The device is able to detect in real time three different stimuli, UV-VIS light, temperature and pH variations. This is thanks to three properties of zinc oxide its photoconductive response, pyroelectricity and surface functionalization with amino-propyl groups, respectively. The three stimuli can be detected either simultaneously or in a sequence/random order. A specific mathematical tool was also developed, together with a design of experiments (DoE), to predict the performances of the sensor. Our micro-device allows reliable and versatile real time measurements of UV-VIS light, temperature and pH variations. Therefore, it shows great potential for use in the field of sensing for living cell cultures. PMID- 27405281 TI - Comments to: Adherence to European Society for Cataract and Refractive Surgery recommendations among Italian cataract surgeons: a survey. PMID- 27405280 TI - Pathway to mental health recovery: a qualitative and quantitative study on the needs of Chinese psychiatric inpatients. AB - BACKGROUND: Exploration of the information and participation needs of psychiatric inpatients is an important step for the implementation of recovery-oriented mental health service. The objective of this study was to explore the information and participation needs of Chinese psychiatric inpatients in the largest psychiatric hospital in Hong Kong. METHODS: The study was divided into two parts. In the first part, eight focus groups with patients, patients' relatives and healthcare professionals were held to identify 22 items of information needs and 16 items of participation needs of Chinese psychiatric inpatients. Basing on the items identified in the first part of the study, a questionnaire was developed to survey on the importance of the different information and participation needs in the second part of the study. Participants were asked to rate in rank order their perceived importance of the items in the questionnaire survey. RESULTS: A hundred and eighty three Chinese psychiatric inpatients completed the questionnaire and the majority of them suffered from schizophrenia (68.3 %). For information needs, the top three needs rated by patients as the most important in descending order were: "Information on the classifications of mental illnesses, signs and symptoms and factors contributing to relapse", "Information on the criteria and arrangements for discharge", and "Information on the importance of psychiatric drug taking and its side effects". For participation needs, the top three needs rated by patients as the most important in descending order were: "Enquiring about personal needs and arrangements", "Keeping in touch with the outside world", and "Learning and practising self-management". CONCLUSIONS: This study reveals that Chinese psychiatric inpatients are concerned about information on their mental illness and its treatments as well as the criteria for discharge. On the other hand, patients are concerned about their personal needs, their self management, as well as their keeping in touch with the outside world during their hospitalisation. Moreover, patients with different socio-demographic and clinical characteristics have different information and participation needs. The results of the present study serve as a reference for designing guidelines, strategies, and programmes to meet the information needs and participation needs of psychiatric inpatients in Hong Kong. PMID- 27405282 TI - Causes of suboptimal corrected visual acuity following phacoemulsification in a teaching university hospital. AB - PURPOSE: Cataract is the leading cause of reversible blindness in developing countries, with variable visual outcome following surgery. This work aims at assessing the outcomes of cataract surgery at Kasr Al Ainy Hospital and identifying the reasons for borderline and poor outcome in the studied group. METHODS: A total of 150 eyes of patients with cataract and no other ocular pathology were included in this study. Uncorrected visual acuity (UCVA) and corrected visual acuity (CVA), complete ocular examination using slit-lamp, applanation tonometry, and ophthalmoscopy were performed for all patients. Biometry for intraocular lens power calculation and operative data were recorded. Patients were followed for 6 weeks; UCVA, CVA, and any complications were noted. RESULTS: Mean preoperative CVA was 0.16 +/- 0.16 (SD) and mean postoperative CVA was 0.66 +/- 0.33 (p<0.001). Forty-two percent of surgeries were performed by junior staff under training. Thirty-five surgeries were complicated by posterior capsular rupture. Mean CVA at 6 weeks in the uncomplicated group was 0.77 +/- 0.22; in the complicated group, 0.28 +/- 0.34 (p<0.001). Biometry was accurate in 51.6% of cases. Most important causes for suboptimal outcome were aphakia, astigmatism, posterior capsular opacification, and corneal edema. CONCLUSIONS: Kasr Al Ainy Hospital achieved CVA 6/9 or more in 69.3% and CVA 6/18 or more in 81.3% of patients. The capsular complication rate was high at 23.3%. The high complication rate is attributed to the nature of the teaching hospital where most surgeons were in their learning periods. PMID- 27405283 TI - Author's reply to comments to: Response to bevacizumab after treatment with aflibercept in eyes with neovascular AMD. PMID- 27405284 TI - Amniotic membrane transplantation with narrow-strip conjunctival autograft vs conjunctival autograft for recurrent pterygia. AB - PURPOSE: To compare amniotic membrane transplantation (AMT) associated with narrow-strip conjunctival autograft vs conjunctival autograft alone for the treatment of recurrent pterygium. METHODS: In this prospective consecutive interventional study, patients with recurrent pterygium were randomly divided into one of 2 groups; group 1: patients undergoing AMT associated with autologous conjunctival graft; and group 2: patients undergoing conjunctival autograft alone. RESULTS: Of the 80 operated eyes included in this study, 39 (group 1, mean patient age 52.1 +/- 11.7 SD years) underwent AMT associated with narrow-strip conjunctival autograft and 41 (group 2, mean patient age 45.8 +/- 12.9 SD years) underwent conjunctival autograft alone. In group 1, 6 eyes (15.4%) had grade 1 pterygium, 19 eyes (48.7%) had grade 2 pterygium, and 14 eyes (35.9%) had grade 3 pterygium. In the second group, 5 eyes (12.2%) had grade 1 pterygium, 18 eyes (43.9%) had grade 2 pterygium, and 14 eyes (35.9%) had grade 3 pterygium. No statistically significant difference was found between the 2 groups (p = 0.752). Of the 39 eyes in group 1, recurrent pterygium was observed in 7 cases (17.9%). However, of the 41 eyes in group 2, recurrent pterygium was observed in only 4 cases (9.75%). No statistically significant difference was found between the 2 groups (p = 0.2684). CONCLUSIONS: The results of this study indicate that conjunctival autograft alone might be a better surgical choice for the treatment of recurrent pterygia than combining it with AMT; however, this second option provides a good surgical alternative in cases where little conjunctival donor tissue is available. PMID- 27405285 TI - Comments to: Response to bevacizumab after treatment with aflibercept in eyes with neovascular AMD. PMID- 27405286 TI - Chorioretinal coloboma in a patient with pancreas divisum: clinical and imaging features. AB - PURPOSE: To report the case of a 61-year-old woman with pancreas divisum and an asymptomatic chorioretinal coloboma in its 2 forms: complete and partial. METHODS: Case report. RESULTS: Dilated fundus examination and photograph revealed a complete and partial coloboma in the right eye. Swept-source optical coherence tomography and swept-source optical coherence tomography angiography (SS-OCTA) were performed. Swept-source optical coherence tomography angiography disclosed the complete coloboma as a black, round, avascular area surrounded by normal vascular tissue in every plexus (i.e., superficial, deep, and choriocapillary). Although irregular and attenuated, the vascular network of the partial coloboma was appreciable in each layer, indicating some degree of vascular preservation. CONCLUSIONS: Chorioretinal coloboma has been linked to several ocular and systemic conditions. To our knowledge, no association between coloboma and pancreas divisum has been reported. In addition, chorioretinal coloboma has not been previously characterized by means of SS-OCTA. PMID- 27405287 TI - Regression of epiretinal membrane after optic nerve atrophy. AB - PURPOSE: To describe a case of epiretinal membrane (ERM) regression after optic nerve atrophy. METHODS: Retrospective case report. RESULTS: A 56-year-old man with progressive visual impairment was found to have an ERM with associated retinal thickening and distortion (documented with spectral-domain optical coherence tomography [OCT]). In addition, we noted a slight unilateral paleness of the optic nerve. The patient denied any further diagnostic investigation and presented himself again 2 years after the initial presentation. A new OCT examination at this point revealed a remarkable regression of the ERM and atrophy of the retinal nerve fiber layer. CONCLUSIONS: Regression of ERM may occur after optic nerve atrophy. A potential causal linkage is suggested based on the atrophy of the retinal nerve fibers and regression of the glial cells. PMID- 27405288 TI - Optical coherence tomography angiography in retinal vein occlusion treated with dexamethasone implant: a new test for follow-up evaluation. AB - PURPOSE: To quantitatively and qualitatively analyze patients with macular edema secondary to retinal vein occlusion (RVO) and treated with the intravitreal dexamethasone implant using optical coherence tomography angiography (OCTA). METHODS: The files of patients treated with intravitreal injection of dexamethasone implant for macular edema secondary to RVO were retrospectively analyzed. Before and after injection, the following data were recorded: best corrected visual acuity (BCVA), central macular thickness (CMT) measured using spectral-domain optical coherence tomography, fluorescein angiography, and OCTA (Optovue, Inc., Fremont, CA, USA). Results of automatic measurement of vascular density of the superficial capillary plexus (SCP) and deep capillary plexus were obtained before and after treatment and compared to those of healthy subjects matched for age and sex. RESULTS: Seven eyes of 7 patients (mean age, 76 years; 57% male) were analyzed, including 3 cases of central RVO and 4 cases of branch RVO. All patients received 1 intravitreal injection of dexamethasone implant. After a mean follow-up of 2 months, CMT significantly decreased from 657 um to 324 um on average and BCVA increased from 20/100 to 20/50 (p = 0.017 and p<0.001, respectively). At the SCP, the mean whole en face vascular density slightly decreased during follow-up from 43.21% to 42.76% (not statistically significant). Vascular densities were largely inferior to those observed in control subjects (p<=0.01 in all quadrants). CONCLUSIONS: This study confirms the potential contribution of OCTA as a novel noninvasive imaging technology that enables a quantitative and qualitative evaluation of the follow-up of macular edema in RVO. Optical coherence tomography angiography may complement advantageously multimodal imaging to monitor patients with RVO. PMID- 27405289 TI - Pediatric choroidal neovascularization: should we be more afraid of Virginia Woolf or of the big bad wolf? PMID- 27405290 TI - Real-time assessment of intraoperative vaulting in implantable collamer lens and correlation with postoperative vaulting. AB - PURPOSE: To assess the intraoperative vaulting in patients undergoing implantable collamer lens (ICL) implantation with microscope-integrated intraoperative optical coherence tomography (iOCT) and correlate it with the postoperative vaulting. METHODS: Forty eyes of 22 consecutive patients undergoing ICL implantation were prospectively evaluated. Vaulting was measured intraoperatively using microscope-integrated iOCT. The ICL-lenticular relationship was dynamically assessed throughout the surgery. Postoperative vaulting was measured using anterior segment optical coherence tomography on the first postoperative day and after 1 month and compared with the intraoperative vaulting. Uncorrected and best corrected Snellen visual acuity, intraocular pressure (IOP), and anterior and posterior segments were assessed in all cases. RESULTS: The mean central vaulting noted intraoperatively was 558.4 +/- 122.8 um. Postoperative mean vaulting was 576.0 +/- 131.2 um on day 1 and 551.1 +/- 122.5 um on day 30. There was a significant correlation between the intraoperative and the postoperative day 1 vaulting (paired samples correlation: 0.969, p<0.001) and day 30 vaulting (paired samples correlation: 0.945, p<0.001). An ICL-lenticular touch was not noted at any time during the surgery. The postoperative course was uneventful and no patient developed raised IOP or lenticular changes by the last follow-up. CONCLUSIONS: Intraoperative vaulting correlates well with postoperative vaulting and can aid in on-table detection of extremes of vaulting and decision-making. It enhances the safety of the surgical procedure by providing a real-time display of the intraoperative manipulations. PMID- 27405291 TI - Could lower leg Wartenberg test be used as a predictor of restrictions in temporomandibular joint movements in CP patients? AB - PURPOSE: Patients with spasticity suffer not only from neurological problems but also from various dentistry problems due to spasticity of the jaw muscles. Measurements of motion in temporomandibular joints should reflect the amount of abnormal muscle tone of these muscles. The aim of this study was to find out if the measurements of temporomandibular joint movements performed with the ultrasound Zebris device are different in cerebral palsy patients than in healthy subjects; and to find out if the information on the degree of spasticity in the lower legs provided by the Wartenberg test could be used to predict the degree of spasticty in the jaw muscles. METHOD: Twenty five healthy subjects and 25 cerebral palsy patients participated in the study. Two types of measurements were performed: temporomandibular movements measured with Zebris device, and instrumented Wartenberg test. RESULTS: The laterotrusion and opening movements are different in CP patients than in healthy subjects. Laterotrusion movement correlates with velocity measured during the Wartenberg test. CONCLUSION: This finding suggests that high spasticity in the lower legs could indicate jaw movement restrictions in CP patients. PMID- 27405292 TI - Emotion and aggressive intergroup cognitions: The ANCODI hypothesis. AB - Previous research has suggested an important role for the emotion of hatred in intergroup aggression. Recent theoretical and empirical work has strongly suggested that the combination of anger, contempt, and disgust (ANCODI) comprise the basic elements of hatred, and are the key emotions associated with intergroup aggression. No study, however, has provided evidence that these emotions cause hostile cognitions about specific groups. We report two studies that provide initial evidence. In both, participants were members of ideologically motivated groups and were primed with ANCODI. In Study 1 participants primed with ANCODI produced more aggressive cognitions relative to their opponent outgroup than a neutral outgroup; this effect did not occur for participants primed with fear sadness. In Study 2 participants primed with ANCODI engaged in more competitive decision making against their opponent outgroups than a neutral outgroup; this effect did not occur for participants primed with disgust only. These findings contribute to the literature on the role of emotion in intergroup aggression and hostility, and provide a more nuanced view of the role of emotions in intergroup relations, possibly identifying the basic emotional elements of hatred. Aggr. Behav. 43:93-107, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27405293 TI - Minimally invasive treatment of difficult bleeding lesions of the small bowel. AB - BACKGROUND: Bleeding Lesions of the small bowel are often difficult to identify due to the obscure symptomatology. Localizing these lesions requires specific techniques. The Double- balloon enteroscopy (DBE) could be used to precisely localize and mark lesions, so that a minimally invasive surgical treatment could be performed. PATIENTS & METHODS: 20 robot-assisted small bowel procedures are presented using a combination of DBE for localization and robotic resection. RESULTS: There were 10 jejunal resections and 10 ileal resections. Mean age was 58.7 years. Mean operative time was 153.4 minutes, mean blood loss of 46 ml. No conversion-to-open and there were 4 post-operative complications. The 90-day mortality was nil and the median LOS was 4.1 days. Final pathology was consistent with malignancy in 10 cases. CONCLUSIONS: The combination of double balloon enteroscopy and robotic technology allows accurate identification and selective treatment of lesions that could be otherwise difficult to treat in a minimally invasive fashion. PMID- 27405295 TI - Pooled analysis of the reports of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma. AB - PURPOSE: The purpose of this study was to better understand the efficacy and safety of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma(R/RMM). METHODS: We retrieved and reviewed published reports including carfilzomib, panobinostat, and elotuzumab combination regimens for patients with R/RMM. RESULTS: We identified 20 prospective studies that evaluated 2220 patients. Carfilzomib combination regimens produced an overall response rate (ORR >= PR) of 61 % in the 1211 relapsed/refractory patients. At least very good partial response (VGPR) was 29 % in patients with carfilzomib combinations. Finally, 49 % of the 597 patients achieved ORR in patients receiving panobinostat-containing combinations. At least VGPR was 16 % in patients with panobinostat combinations. Three hundred twenty-eight of these 449 patients (73 %) receiving elotuzumab-containing combinations achieved ORR. And at least VGPR was 37 %. And, the vital nonhematologic adverse events (AEs) were cardiac events and pneumonia. CONCLUSION: Carfilzomib, panobinostat, and elotuzumab combination regimens produced clinical benefits in patients with R/RMM. PMID- 27405297 TI - Vesicles Are Persistent Features of Different Plastids. AB - Peripheral vesicles in plastids have been observed repeatedly, primarily in proplastids and developing chloroplasts, in which they are suggested to function in thylakoid biogenesis. Previous observations of vesicles in mature chloroplasts have mainly concerned low temperature pretreated plants occasionally treated with inhibitors blocking vesicle fusion. Here, we show that such vesicle-like structures occur not only in chloroplasts and proplastids, but also in etioplasts, etio-chloroplasts, leucoplasts, chromoplasts and even transforming desiccoplasts without any specific pretreatment. Observations are made both in C3 and C4 species, in different cell types (meristematic, epidermis, mesophyll, bundle sheath and secretory cells) and different organs (roots, stems, leaves, floral parts and fruits). Until recently not much focus has been given to the idea that vesicle transport in chloroplasts could be mediated by proteins, but recent data suggest that the vesicle system of chloroplasts has similarities with the cytosolic coat protein complex II system. All current data taken together support the idea of an ongoing, active and protein-mediated vesicle transport not only in chloroplasts but also in other plastids, obviously occurring regardless of chemical modifications, temperature and plastid developmental stage. PMID- 27405296 TI - Effects of extended-release niacin/laropiprant on correlations between apolipoprotein B, LDL-cholesterol and non-HDL-cholesterol in patients with type 2 diabetes. AB - BACKGROUND: LDL-C, non-HDL-C and ApoB levels are inter-correlated and all predict risk of atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM) and/or high TG. These levels are lowered by extended release niacin (ERN), and changes in the ratios of these levels may affect ASCVD risk. This analysis examined the effects of extended-release niacin/laropiprant (ERN/LRPT) on the relationships between apoB:LDL-C and apoB:non-HDL-C in patients with T2DM. METHODS: T2DM patients (n = 796) had LDL-C >=1.55 and <2.97 mmol/L and TG <5.65 mmol/L following a 4-week, lipid-modifying run-in (~78 % taking statins). ApoB:LDL-C and apoB:non-HDL-C correlations were assessed after randomized (4:3), double-blind ERN/LRPT or placebo for 12 weeks. Pearson correlation coefficients between apoB:LDL-C and apoB:non-HDL-C were computed and simple linear regression models were fitted for apoB:LDL-C and apoB:non-HDL-C at baseline and Week 12, and the correlations between measured apoB and measured vs predicted values of LDL-C and non-HDL-C were studied. RESULTS: LDL-C and especially non-HDL-C were well correlated with apoB at baseline, and treatment with ERN/LRPT increased these correlations, especially between LDL-C and apoB. Despite the tighter correlations, many patients who achieved non-HDL-C goal, and especially LDL-C goal, remained above apoB goal. There was a trend towards greater increases in these correlations in the higher TG subgroup, non significant possibly due to the small number of subjects. CONCLUSIONS: ERN/LRPT treatment increased association of apoB with LDL-C and non-HDL-C in patients with T2DM. Lowering LDL-C, non-HDL-C and apoB with niacin has the potential to reduce coronary risk in patients with T2DM. PMID- 27405298 TI - Thermodesulfatator autotrophicus sp. nov., a thermophilic sulfate-reducing bacterium from the Indian Ocean. AB - A novel sulfate-reducing bacterium, strain S606T, was isolated from a sulfide sample collected at a depth of 2764 m from a deep-sea vent chimney wall in the Indian Ocean. Phylogenetic 16S rRNA gene sequence analyses placed strain S606T within the genus Thermodesulfatator, with highest sequence similarity of 98.2 % to Thermodesulfatator indicus DSM 15286T, followed by Thermodesulfatator atlanticus AT1325T (97.4 %). The average nucleotide identity (ANI) values between S606T and the two other type strains (T. indicus DSM 15286T and T. atlanticus AT1325T) were 79.2 % and 71.5 %, respectively. The digital DNA-DNA hybridization estimate values between S606T and these two type strains were 22.7+/-2.4 % and 18.1+/-2.3 %, respectively. Cells were Gram-stain-negative, anaerobic, motile rods (1-1.8*0.5-0.7 um). The novel isolate grew at NaCl concentrations ranging from 1.5 to 4.5 % (optimum 2.5-3 %), from pH 5.5 to 8 (optimum 6.5-7.0) and at temperatures between 50 and 80 degrees C (optimum 65-70 degrees C). S606T grew chemolithoautotrophically in an H2/CO2 atmosphere (80 : 20, v/v; 200 kPa), used sulfate as a terminal electron acceptor, but not sulfur, sulfite nor thiosulfate. The predominant fatty acids were C16 : 0 (24.2 %), summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c, 26.3 %), C18 : 0 (22.2 %) and C18 : 1omega9c (9.2 %). The DNA G+C content of the chromosomal DNA was 43.1 mol%. The combined genotypic, chemotaxonomic and phenotypic traits show that S606T should be described as representing a novel species of the genus Thermodesulfatator, for which the name Thermodesulfatator autotrophicus sp. nov. is proposed. The type strain is S606T (=DSM 101864T=MCCC 1A01871T). PMID- 27405299 TI - Imposing antecedent global change conditions rapidly alters plant community composition in a mixed-grass prairie. AB - Global change drivers are altering climatic and edaphic conditions of ecosystems across the globe, and we expect novel plant communities to become more common as a result. In the Colorado Front Range, compositional changes have occurred in the mixed-grass prairie plant community in conjunction with shifts in winter precipitation and atmospheric nitrogen (N) deposition. To test whether these environmental changes have been responsible for the observed plant community change, we conducted an in situ manipulative experiment in a mixed-grass meadow near Boulder, CO. We simulated historical conditions by reducing N availability (+500 g C m(-2) year(-1)) and winter precipitation (with rainout shelters) for 2 years (2013-2014) and compared vegetation response to these treatments with that of ambient conditions. The site experienced an extreme precipitation event in autumn 2013 which allowed comparison of an exceptionally wet year with an average year. We measured pre-treatment species composition in 2012, and treatment responses in the spring and summer of 2013 and 2014. As predicted, simulating historical low N-winter dry conditions resulted in a plant community dominated by historically abundant species. Cool-season introduced species were significantly reduced in low N-winter dry plots, particularly the annual plants Bromus tectorum and Alyssum parviflorum. These same species responded strongly to the extreme precipitation event with large increases, while native grasses and forbs showed little change in productivity or composition under varying climatic or edaphic conditions. This work provides clear evidence linking on-going global change drivers to altered plant community composition in an otherwise relatively undisturbed grassland ecosystem. PMID- 27405305 TI - Vitamin supplementation in pregnancy. AB - Ensuring that a woman is well-nourished, both before and during pregnancy, is crucial for the health of the woman and that of the unborn child.(1) Maternal deficiency in key nutrients has been linked to pre-eclampsia, restricted fetal growth, neural tube defects, skeletal deformity and low birth weight.(1,2) Many nutritional supplements containing vitamins, minerals and other micronutrients are heavily marketed to women for all stages of pregnancy. However, much of the evidence for vitamin supplementation in pregnancy comes from studies carried out in low-income countries,(3) where women are more likely to be undernourished or malnourished than within the UK population. The challenges lie in knowing which supplements are beneficial and in improving uptake among those at most need. Here we summarise current UK guidance for vitamin supplementation in pregnancy and review the evidence behind it. PMID- 27405300 TI - Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset. AB - Type II natural killer T cells (NKT) are a subset of the innate-like CD1d restricted lymphocytes that are reactive to lipid antigens. Unlike the type I NKT cells, which express a semi-invariant TCR, type II NKT cells express a broader TCR repertoire. Additionally, other features, such as their predominance over type I cells in humans versus mice, the nature of their ligands, CD1d/lipid/TCR binding, and modulation of immune responses, distinguish type II NKT cells from type I NKT cells. Interestingly, it is the self-lipid-reactivity of type II NKT cells that has helped define their physiological role in health and in disease. The discovery of sulfatide as one of the major antigens for CD1d-restricted type II NKT cells in mice has been instrumental in the characterization of these cells, including the TCR repertoire, the crystal structure of the CD1d/lipid/TCR complex, and their function. Subsequently, several other glycolipids and phospholipids from both endogenous and microbial sources have been shown to activate type II NKT cells. The activation of a specific subset of type II NKT cells following administration with sulfatide or lysophosphatidylcholine (LPC) leads to engagement of a dominant immunoregulatory pathway associated with the inactivation of type I NKT cells, conventional dendritic cells, and inhibition of the proinflammatory Th1/Th17 cells. Thus, type II NKT cells have been shown to be immunosuppressive in autoimmune diseases, inflammatory liver diseases, and in cancer. Knowing their relatively higher prevalence in human than type I NKT cells, understanding their biology is imperative for health and disease. PMID- 27405306 TI - Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly. AB - PURPOSE: Cushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia. METHODS: Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed. RESULTS: The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3-67.0 %) than in patients with CD treated with pasireotide SC (68.4-73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791-799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875-884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320-326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914-924, 2012, 6.0 %). Hyperglycemia related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues. CONCLUSIONS: Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly. Hyperglycemic effects associated with pasireotide have a predictable pattern, can be managed with antidiabetic agents, and are reversible upon discontinuation. PMID- 27405307 TI - Maurice Simeon Albin. PMID- 27405308 TI - Radiographic Evaluation of Intermetatarsal Angle Correction Following First MTP Joint Arthrodesis for Severe Hallux Valgus. AB - BACKGROUND: Arthrodesis is a standard operative treatment for symptomatic arthritis of the first metatarsophalangeal (MTP) joint. Patients with degenerative joint disease (DJD), severe hallux valgus, and metatarsus primus varus may also require fusion of the first MTP joint. An important question in the latter group of patients is whether a proximal first metatarsal osteotomy is required, in addition to the first MTP joint fusion. Our hypothesis was that patients with severe hallux valgus and metatarsus primus varus, treated with first MTP joint arthrodesis alone, would have correction of the first-to-second intermetatarsal angle (1-2 IMA) and hallux valgus angle (HVA) to near population norms, without the addition of a proximal first metatarsal osteotomy. METHODS: Preoperative and postoperative radiographs of 19 feet, in 17 patients, with preoperative IMA greater than 15 were analyzed. Weight-bearing radiographs were divided into pre- and postoperative cohorts. Three independent reviewers measured these radiographs and mean 1-2 IMA and HVA were calculated. Mean follow-up was 10 months. RESULTS: The mean preoperative 1-2 IMA was 19.2 degrees (15.6-24.3). The mean preoperative HVA was 48.5 (36-56.6). The mean postoperative values for 1-2 IMA and HVA were 10.8 and 12.3 degrees, respectively. The mean change in IMA was 8.3 degrees and in the hallux valgus angle was 36.4 degrees. The differences between pre- and postoperative measurement for both angles were statistically significant (P < .001). Seven of 19 (37%) feet were corrected to an IMA of less than 9 degrees (normal), whereas in 15/19 feet the postoperative IMA was 12.3 degrees or less. The postoperative HVA was less than 15 degrees in 15/19 (79%) feet. CONCLUSION: This pre- and postoperative radiographic analysis of patients with severe bunion deformity demonstrated that HVA and 1-2 IMA were acceptably corrected without the addition of a proximal first metatarsal osteotomy. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 27405309 TI - Follow-up CT pulmonary angiograms in patients with acute pulmonary embolism. AB - Computed tomographic (CT) angiography is associated with a non-negligible lifetime attributable risk of cancer. The risk is considerably greater for women and younger patients. Recognizing that there are risks from radiation, the purpose of this investigation was to assess the frequency of follow-up CT angiograms in patients with acute pulmonary embolism. This was a retrospective cohort study of patients aged >=18 years with acute pulmonary embolism seen in three emergency departments from January 2013 to December 2014. Records of all patients were reviewed for at least 14 months. Pulmonary embolism was diagnosed by CT angiography in 600 patients. At least one follow-up CT angiogram in 1 year was obtained in 141 of 600 (23.5 %). Two follow-ups in 1 year were obtained in 40 patients (6.7 %), 3 follow-ups were obtained in 15 patients (2.5 %), and 4 follow ups were obtained in 3 patients (0.5 %). Among young women (aged <=29 years) with pulmonary embolism, 10 of 21 (47.6 %) had at least 1 follow-up and 4 of 21 (19.0 %) had 2 or more follow-ups in 1 year. Among all patients, recurrent pulmonary embolism was diagnosed in 15 of 141 (10.6 %) on the first follow-up CT angiogram and in 6 of 40 (15.0 %) on the second follow-up. Follow-up CT angiograms were obtained in a significant proportion of patients with pulmonary embolism, including young women, the group with the highest risk. Alternative options might be considered to reduce the hazard of radiation-induced cancer, particularly in young women. PMID- 27405310 TI - Effect of Anti-TNF Agents on Postoperative Outcomes in Inflammatory Bowel Disease Patients: a Single Institution Experience. AB - BACKGROUND: Anti-tumor necrosis factor (TNF) agents have been an integral part in the treatment of inflammatory bowel disease. However, a subset of inflammatory bowel disease patients ultimately requires surgery and up to 30 % of them have undergone treatment with anti-TNF agents. Studies assessing the effect of anti TNF agents on postoperative outcomes have been inconsistent. The aim of this study is to assess postoperative morbidity in inflammatory bowel disease patients who underwent surgery with anti-TNF therapy prior to surgery. METHODS: This is a retrospective review of 282 patients with inflammatory bowel disease undergoing intestinal surgery between 2013 and 2015 at the Mount Sinai Hospital. Patients were divided into two groups based on treatment with anti-TNF agents (infliximab, adalimumab, certolizumab) within 8 weeks of surgery. Thirty-day postoperative outcomes were recorded. Univariate and multivariate statistical analyses were carried out. RESULTS: Seventy-three patients were treated with anti-TNF therapy within 8 weeks of surgery while 209 patients did not have exposure. Thirty-day anastomotic leak, intra-abdominal abscess, wound infection, extra-abdominal infection, readmission, and mortality rates were not significantly different between the two groups. CONCLUSIONS: The use of anti-TNF medications in inflammatory bowel disease patients within 2 months of intestinal surgery is not associated with an increased risk of 30-day postoperative complications. PMID- 27405311 TI - Lipoprotein-like particles in a prokaryote: quinone droplets of Thermoplasma acidophilum. AB - Cytosolic, globular droplets with an average diameter of 50 nm were observed in vitrified Thermoplasma acidophilum cells by means of cryo-electron tomography. These droplets were isolated by column chromatography and immunoprecipitation protein purification methods. Subsequent chemical and biochemical analyses identified lipid and protein components, respectively. Two major lipid components, comigrating menaquinones at the solvent front and the slower migrating Thermoplasma polar lipid U4, were detected by TLC experiments. The major protein component was identified as the 153 amino acid long Ta0547 vitellogenin-N domain protein. This domain has been found so far exclusively in large lipid transport proteins of vertebrates and non-vertebrates. Blast protein database homology searches with Ta0547 did not return any eukaryal hits; homologous sequences were found only in thermo-acidophilic archaeons. However, a profile-sequence domain search performed with the vitellogenin-N domain (PF01347) hmm-profile against the T. acidophilum proteome returned Ta0547 as hit. Electron microscopy appearance of isolated droplets resembled to lipoprotein particles. However, no (tetraether) lipid layer could be detected on the droplets surface, rather hydrophobic compounds of the electron dense lumen were surrounded by a denser discontinuous protein boundary. Based on described features, these particles qualify for a novel lipoprotein particle category, what we nominated Thermoplasma Quinone Droplet. PMID- 27405313 TI - Phenotypic characterization of epibulbar dermoids. AB - The purpose of this study was to characterize the phenotypic presentation, clinical course, and outcomes of epibulbar dermoids (EpDs) which are the most common congenital eye tumor in children. Sixty-eight dermoids were identified in 58 eyes of 48 patients of Seattle Children's Hospital between 1981 and 2014 via electronic medical record search. Patients were organized into: "EpD-Only" [patients without other congenital anomalies (n = 13)], "EpD-CFM" [patients with a craniofacial microsomia (CFM) diagnosis (n = 25)], and "EpD-Other" [patients with other congenital anomalies (n = 10)]. All EpD in the EpD-Only group were unilateral and singular, while the EpD-CFM group had six cases with multiple unilateral EpD and five cases with bilateral EpD. In the EpD-Only group, 69 % of EpD were left sided, whereas in the EpD-CFM group, there was no side predisposition. Among both groups, the majority of EpD were limbal or lipodermoids in the inferotemporal quadrant of the eye. Surgery was more common and at a younger age in the EpD-CFM group than the EpD-Only group (56 vs. 38 %, 5.2 vs. 7.0 years). Follow-up surgeries occurred only in the EpD-CFM group (21 %). EpDs were most commonly associated with preauricular tags, congenital heart defects, genitourinary, and nervous system anomalies. Whereas the location and type of EpDs did not significantly differ between the groups, the phenotype in the EpD-Only group appears to be less complex. This may indicate an important difference between EpDs in isolation and those within CFM. Additional studies will further characterize these phenotypes and outcomes. PMID- 27405312 TI - Computational fluid dynamics of cerebral aneurysm coiling using high-resolution and high-energy synchrotron X-ray microtomography: comparison with the homogeneous porous medium approach. AB - BACKGROUND: Computational modeling of intracranial aneurysms provides insights into the influence of hemodynamics on aneurysm growth, rupture, and treatment outcome. Standard modeling of coiled aneurysms simplifies the complex geometry of the coil mass into a homogeneous porous medium that fills the aneurysmal sac. We compare hemodynamics of coiled aneurysms modeled from high-resolution imaging with those from the same aneurysms modeled following the standard technique, in an effort to characterize sources of error from the simplified model. MATERIALS: Physical models of two unruptured aneurysms were created using three-dimensional printing. The models were treated with coil embolization using the same coils as those used in actual patient treatment and then scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the coil mass. Computational modeling of each aneurysm was performed using patient-specific boundary conditions. The coils were modeled using the simplified porous medium or by incorporating the X-ray imaged coil surface, and the differences in hemodynamic variables were assessed. RESULTS: X-ray microtomographic imaging of coils and incorporation into computational models were successful for both aneurysms. Porous medium calculations of coiled aneurysm hemodynamics overestimated intra aneurysmal flow, underestimated oscillatory shear index and viscous dissipation, and over- or underpredicted wall shear stress (WSS) and WSS gradient compared with X-ray-based coiled computational fluid dynamics models. CONCLUSIONS: Computational modeling of coiled intracranial aneurysms using the porous medium approach may inaccurately estimate key hemodynamic variables compared with models incorporating high-resolution synchrotron X-ray microtomographic imaging of complex aneurysm coil geometry. PMID- 27405314 TI - Contrast-enhanced T2-FLAIR MR imaging in patients with uveitis. AB - To report MRI findings which reflect a pathological inflammatory condition of the uveal tract. This study includes single-center retrospective case series of five patients with clinical diagnosis of uveitis. There were 1 male (20 %) and 4 female patients (80 %). The average age was 29.6 years (range 25-38 years). Patients and 50 age-range-matched control subjects were scanned using a 1.5 T scanner. Ten additional control subjects scanned at 3 T were evaluated to have reference images at that high field. All patients (n = 5, 100 %) presented uveal tract enhancement on post-contrast T2-FLAIR fat-suppressed images and only 2 (40 %) had enhancement on T1-weighted images. The enhancement was anterior in 2 (40 %), pan-uveal in 2 (40 %), and posterior in 1 patient (20 %). Two patients (40 %) had unilateral increased vitreous signal on T2-FLAIR. One patient (20 %) had bilateral retrobulbar fat enhancement in both post-contrast T2-FLAIR and T1 weighted images. Post-contrast T2-FLAIR images can reveal abnormal enhancement of the uveal tract and retrobulbar fat as well as increased vitreous signal in patients with uveitis. In our small series, the sensitivity of post-contrast T2 FLAIR was higher than the conventional post-contrast T1-weighted images. Nonetheless, when bilateral uveal tract enhancement is present, there should be discretion before calling uveitis because the finding has been reported in different eye conditions as well as in a small percentage of healthy subjects at 1.5 T. In addition, it should be noted that post-contrast T2-FLAIR enhancement of the uveal tract is a normal finding at 3 T imaging. PMID- 27405315 TI - [Histopathology of IgG4-related disease]. AB - At an international consensus conference in 2011, multifocal chronic fibrosing inflammatory processes, which are associated with elevated IgG4 serum levels and/or tissue infiltration with IgG4 positive plasma cells, were recognized as a distinct disease entity called IgG4-related disease (IgG4-RD). As IgG4-RD responds well to steroid treatment but imitates a tumor in many organs, particularly in the pancreas, a biopsy for confirmation of the diagnosis is often warranted. The histological criteria for IgG4-RD as defined in 2011 are based on the following main features: 1) dense lymphoplasmacytic infiltrate, 2) storiform fibrosis and 3) obliterative phlebitis. The diagnosis is further supported by immunohistochemical demonstration of an increased infiltration of IgG4-positive plasma cells and an elevated IgG4/IgG ratio. The morphological criteria of IgG4 RD are in most cases detectable in biopsies and can significantly contribute to the diagnosis of this disease, in concert with clinical, serological (elevated serum IgG4 level) and radiological features. PMID- 27405316 TI - A Novel Model of Dexamethasone-Induced Hypertension: Use in Investigating the Role of Tyrosine Hydroxylase. AB - Our objective was to study hypertension induced by chronic administration of synthetic glucocorticoid, dexamethasone (DEX), under nonstressful conditions and examine the role of catecholamine biosynthesis. To achieve this, we did the following: 1) used radiotelemetry to record mean arterial pressure (MAP) and heart rate (HR) in freely moving rats, and 2) administered different doses of DEX in drinking water. To evaluate the involvement of tyrosine hydroxylase (TH), the rate-limiting step in catecholamine biosynthesis, we treated rats with the TH inhibitor, alpha-methyl-para-tyrosine (alpha-MPT), for 3 days prior to administration of DEX and assessed TH mRNA and protein expression by quantitative real-time polymerase chain reaction and Western blot in the adrenal medulla. We observed a dose-dependent elevation in blood pressure with a DEX dose of 0.3 mg/kg administered for 10 days, significantly increasing MAP by +15.0 +/- 1.1 mm Hg, while concomitantly reducing HR. Although this DEX treatment also significantly decreased body weight, pair-fed animals that showed similar decreases in body weight due to lowered food intake were not hypertensive, suggesting that body weight changes may not account for DEX-induced hypertension. Chronic DEX treatment significantly increased the TH mRNA and protein levels in the adrenal medulla, and alpha-MPT administration not only reduced DEX pressor effects, but also inhibited TH (serine(40)) phosphorylation. Our study thus validates a novel model to study hypertension induced by chronic intake of DEX in freely moving rats not subject to the confounding factors of previous models and establishes its dependence on concomitant activation of peripheral catecholamine biosynthesis. PMID- 27405317 TI - The effect of bereavement groups on grief, anxiety, and depression - a controlled, prospective intervention study. AB - ABSTACT: BACKGROUND: Bereavement groups are believed to be beneficial as preventive interventions to reduce the development of complicated grief for people at risk after the death of a significant other. This study aimed to investigate whether measurable effects on grief, anxiety, and depression could be detected in those participating in bereavement groups compared to non participating controls. METHODS: Questionnaires covering the Texas Revised Inventory of Grief (TRIG), the Hospital Anxiety and Depression Scale (HADS), and background questions were handed out pre-intervention, five weeks and one year post-intervention to bereaved caregivers invited to bereavement groups. The results were analysed with non-parametric methods. RESULTS: A total of 124 individuals answered the questionnaires, and were divided into three categories: participants, non-participants unable to participate, and non-participants not wanting to participate in bereavement groups. At the one-year follow up, participants and those unable to participate reported higher levels of grief and were more anxious than those not wanting to participate. Depression did not differ between the groups. CONCLUSIONS: Participation in bereavement groups did not produce any effects on grief, anxiety, or depression in comparison to non participants who were unable to participate. Non-participants who did not want to participate reported lower levels of grief and anxiety than the other two groups. PMID- 27405318 TI - A value proposition for early physical therapist management of neck pain: a retrospective cohort analysis. AB - BACKGROUND: Neck pain is one of the most common reasons for entry into the healthcare system. Recent increases in healthcare utilization and medical costs have not correlated with improvements in health. Therefore there is a need to identify management strategies for neck pain that are effective for the patient, cost efficient for the payer and provided at the optimal time during an episode of neck pain. METHODS: One thousand five hundred thirty-one patients who underwent physical therapist management with a primary complaint of non-specific neck pain from January 1, 2008 to December 31, 2012 were identified from the Rehabilitation Outcomes Management System (ROMS) database at Intermountain Healthcare. Patients reporting duration of symptoms less than 4 weeks were designated as undergoing "early" management and patients with duration of symptoms greater than 4 weeks were designated as receiving "delayed" management. These groups were compared using binary logistic regression to examine odds of achieving Minimal Clinically Important Difference (MCID) on the Neck Disability Index (NDI) and Numerical Pain Rating Scale (NPRS). Separate generalized linear modeling examined the effect of timing of physical therapist management on the metrics of value and efficiency. RESULTS: Patients who received early physical therapist management had increased odds of achieving MCID on the NDI (aOR = 2.01, 95 % CI 1.57, 2.56) and MCID on the NPRS (aOR = 1.82, 95 % CI 1.42, 2.38), when compared to patients receiving delayed management. Patients who received early management demonstrated the greatest value in decreasing disability with a 2.27 percentage point change in NDI score per 100 dollars, best value in decreasing pain with a 0.38 point change on the NPRS per 100 dollars. Finally, patients receiving early management were managed more efficiently with a 3.44 percentage point change in NDI score per visit and 0.57 point change in NPRS score per visit. CONCLUSIONS: These findings suggest that healthcare systems that provide pathways for patients to receive early physical therapist management of neck pain may realize improved patient outcomes, greater value and higher efficiency in decreasing disability and pain compared to delayed management. Further research is needed to confirm this assertion. PMID- 27405319 TI - Relationship between performances of 10-time-repeated sit-to-stand and maximal walking tests in non-disabled older women. AB - AIM: Sit-to-stand (STS) test is extensively used to assess the functionality of the lower body in elderly people. This study aimed to examine how the score of STS can be associated with that of maximal walking (MW) tests through a cross sectional as well as longitudinal analysis for non-disabled older women. METHOD: Times taken for a 10-time-repeated STS (STS time) and 5-m MW (MW time) were determined before (pre) and after (post) a 3-month body mass-based exercise program in 154 non-disabled women aged 60 to 79 years. In addition to the time scores, STS and MW power indexes (STS-PI and MW-PI, respectively) were calculated using the following equations: STS-PI = (body height - 0.4) * body mass * 10/STS time and MW-PI = body mass * 5/MW time. RESULTS: At pre- and post-intervention, STS-PI was significantly correlated to MW-PI, with higher correlation coefficients (r = 0.545-0.567, P < 0.0001) than those between the two time scores (r = 0.271-0.309, P < 0.001). The intervention significantly improved STS-time (13.6 +/- 3.2 s at pre to 9.4 +/- 1.8 s at post, P < 0.0001), MW time (2.4 +/- 0.3 s to 2.2 +/- 0.3 s, P < 0.0001), STS-PI (46.5 +/- 12.5 to 65.7 +/- 12.7, P < 0.0001), and MW-PI (112.1 +/- 20.2 to 124.2 +/- 24.4, P < 0.0001). There were significant correlations between the changes of STS and MW times (r = 0.281, P < 0.001) and between those of STS-PI and MW-PI (r = 0.366, P < 0.0001). CONCLUSION: In elderly women, the performance of sit-to-stand task and its training-induced gain are associated with those of the maximal walking task. In addition, the current results indicated that translation of the performance scores of the sit to-stand and maximal walking tasks to power indexes may be a useful approach for examining the association between the two tasks. PMID- 27405320 TI - Genomic characterization of plant cell wall degrading enzymes and in silico analysis of xylanases and polygalacturonases of Fusarium virguliforme. AB - BACKGROUND: Plant cell wall degrading enzymes (PCWDEs) are a subset of carbohydrate-active enzymes (CAZy) produced by plant pathogens to degrade plant cell walls. To counteract PCWDEs, plants release PCWDEs inhibitor proteins (PIPs) to reduce their impact. Several transgenic plants expressing exogenous PIPs that interact with fungal glycoside hydrolase (GH)11-type xylanases or GH28-type polygalacturonase (PG) have been shown to enhance disease resistance. However, many plant pathogenic Fusarium species were reported to escape PIPs inhibition. Fusarium virguliforme is a soilborne pathogen that causes soybean sudden death syndrome (SDS). Although the genome of F. virguliforme was sequenced, there were limited studies focused on the PCWDEs of F. virguliforme. Our goal was to understand the genomic CAZy structure of F. viguliforme, and determine if exogenous PIPs could be theoretically used in soybean to enhance resistance against F. virguliforme. RESULTS: F. virguliforme produces diverse CAZy to degrade cellulose and pectin, similar to other necrotorphic and hemibiotrophic plant pathogenic fungi. However, some common CAZy of plant pathogenic fungi that catalyze hemicellulose, such as GH29, GH30, GH44, GH54, GH62, and GH67, were deficient in F. virguliforme. While the absence of these CAZy families might be complemented by other hemicellulases, F. virguliforme contained unique families including GH131, polysaccharide lyase (PL) 9, PL20, and PL22 that were not reported in other plant pathogenic fungi or oomycetes. Sequence analysis revealed two GH11 xylanases of F. virguliforme, FvXyn11A and FvXyn11B, have conserved residues that allow xylanase inhibitor protein I (XIP-I) binding. Structural modeling suggested that FvXyn11A and FvXyn11B could be blocked by XIP-I that serves as good candidate for developing transgenic soybeans. In contrast, one GH28 PG, FvPG2, contains an amino acid substitution that is potentially incompatible with the bean polygalacturonase-inhibitor protein II (PvPGIP2). CONCLUSIONS: Identification and annotation of CAZy provided advanced understanding of genomic composition of PCWDEs in F. virguliforme. Sequence and structural analyses of FvXyn11A and FvXyn11B suggested both xylanases were conserved in residues that allow XIP-I inhibition, and expression of both xylanases were detected during soybean roots infection. We postulate that a transgenic soybean expressing wheat XIP-I may be useful for developing root rot resistance to F. virguliforme. PMID- 27405321 TI - Case control study: magnetic resonance spectroscopy of brain in HIV infected patients. AB - BACKGROUND: In vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies on brain in HIV infected patients have shown significant alteration in neuro biochemicals. METHODS: In this study, we measured the neuro-biochemical metabolites from the left frontal white matter (FWM) and left basal ganglia (BG) caudate head nucleus in 71 subjects that include 30 healthy controls, 20 asymptomatic HIV and 21 HIV patients with CNS lesion. Proton MR spectra were acquired at 3 T MRI system and the concentration (institutional units) of tNAA (N acetylaspartate, NAA + N-acetylaspartylglutamate, NAAG), tCr (Creatine, Cr + phosphocreatine, PCr), choline containing compounds (tCho), glutamate + glutamine (Glx) and lipid and macromolecules at 0.9 ppm were determined using LC Model. RESULTS: In BG, the concentration of tNAA (6.71 +/- 0.64) was decreased and in FWM, the concentration of Glx (20.4 +/- 7.8), tCr (9.14 +/- 3.04) and lipid and macromolecules at 0.9 ppm (8.69 +/- 2.96) were increased in HIV patients with CNS lesion. In healthy controls, the concentration of tNAA in BG was 7.31 +/- 0.47 and concentration of Glx, tCr and lipid and macromolecules in FWM were 15.0 +/- 6.06, 6.95 +/- 2.56, 5.59 +/- 1.56, respectively. CONCLUSION: Reduced tNAA in BG suggests neuronal loss in HIV patients with CNS lesion while increased Glx in FWM may suggest excito-toxicity. In addition, increased levels of tCr in FWM of HIV patients were observed. The study indicates region specific metabolic changes in tNAA, tCr and Glx in brain of HIV infected patients. PMID- 27405323 TI - Telemedical Education: Training Digital Natives in Telemedicine. AB - Telemedicine plays an important role in the delivery of medical care, and will become increasingly prominent going forward. Current medical students are among the first generation of "digital natives" who are well versed in the incorporation of technology into social interaction. These students are well positioned to apply advances in communications to patient care. Even so, providers require training to effectively leverage these opportunities. Therefore, we recommend introducing telemedicine training into medical school curricula and propose a model for incorporation. PMID- 27405322 TI - Effect of nivolumab on health-related quality of life in patients with treatment naive advanced melanoma: results from the phase III CheckMate 066 study. AB - BACKGROUND: Nivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naive patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented. PATIENTS AND METHODS: HRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus >=1 post baseline assessment. RESULTS: Baseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index. CONCLUSIONS: In addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma. PMID- 27405324 TI - Error-rate estimation in discriminant analysis of non-linear longitudinal data: A comparison of resampling methods. AB - Consider longitudinal observations across different subjects such that the underlying distribution is determined by a non-linear mixed-effects model. In this context, we look at the misclassification error rate for allocating future subjects using cross-validation, bootstrap algorithms (parametric bootstrap, leave-one-out, .632 and [Formula: see text]), and bootstrap cross-validation (which combines the first two approaches), and conduct a numerical study to compare the performance of the different methods. The simulation and comparisons in this study are motivated by real observations from a pregnancy study in which one of the main objectives is to predict normal versus abnormal pregnancy outcomes based on information gathered at early stages. Since in this type of studies it is not uncommon to have insufficient data to simultaneously solve the classification problem and estimate the misclassification error rate, we put special attention to situations when only a small sample size is available. We discuss how the misclassification error rate estimates may be affected by the sample size in terms of variability and bias, and examine conditions under which the misclassification error rate estimates perform reasonably well. PMID- 27405325 TI - A Bayesian multi-stage cost-effectiveness design for animal studies in stroke research. AB - Much progress has been made in the area of adaptive designs for clinical trials. However, little has been done regarding adaptive designs to identify optimal treatment strategies in animal studies. Motivated by an animal study of a novel strategy for treating strokes, we propose a Bayesian multi-stage cost effectiveness design to simultaneously identify the optimal dose and determine the therapeutic treatment window for administrating the experimental agent. We consider a non-monotonic pattern for the dose-schedule-efficacy relationship and develop an adaptive shrinkage algorithm to assign more cohorts to admissible strategies. We conduct simulation studies to evaluate the performance of the proposed design by comparing it with two standard designs. These simulation studies show that the proposed design yields a significantly higher probability of selecting the optimal strategy, while it is generally more efficient and practical in terms of resource usage. PMID- 27405326 TI - Non-randomized and randomized stepped-wedge designs using an orthogonalized least squares framework. AB - Randomized stepped-wedge (R-SW) designs are increasingly used to evaluate interventions targeting continuous longitudinal outcomes measured at T-fixed time points. Typically, all units start out untreated, and randomly chosen units switch to intervention at sequential time points until all receive intervention. As randomization is not always feasible, non-randomized stepped-wedge (NR-SW) designs (units switching to intervention are not randomly chosen) have attracted researchers. We develop an orthogonlized generalized least squares framework for both R-SW and NR-SW designs. The variance of the intervention effect estimate depends on the number of steps ( S), length of step sizes ( ts), and number of units ( ns) switched at each step ( s=1,..., S). If all other design parameters are equal, this variance is higher for the NR-SW than for the equivalent R-SW design (particularly if the intercepts of non-randomly stepped switching strata are analyzed as fixed effects). We focus on balanced stepped-wedge (BR-SW, BNR SW) designs (where ts and ns remain constant across s) to obtain insights into optimality for variance of the estimated intervention effect. As previously observed for the BR-SW, the optimal choice for number of time points at each step is also [Formula: see text] for the BNR-SW. In our examples, when compared to BR SW designs, equivalent BNR-SW designs even with intercepts of non-randomly stepped switching strata analyzed using fixed effects sacrifice little efficiency given an intra-unit repeated measure correlation [Formula: see text]. Compared to traditional difference-in-differences designs, optimal BNR-SW designs are more efficient with the ratio of variances of these designs converging to 0.75 when T > 10. We illustrate these findings using longitudinal outcomes in long-term care facilities. PMID- 27405327 TI - Statistical approaches to account for missing values in accelerometer data: Applications to modeling physical activity. AB - Physical inactivity is a recognized risk factor for many chronic diseases. Accelerometers are increasingly used as an objective means to measure daily physical activity. One challenge in using these devices is missing data due to device nonwear. We used a well-characterized cohort of 333 overweight postmenopausal breast cancer survivors to examine missing data patterns of accelerometer outputs over the day. Based on these observed missingness patterns, we created psuedo-simulated datasets with realistic missing data patterns. We developed statistical methods to design imputation and variance weighting algorithms to account for missing data effects when fitting regression models. Bias and precision of each method were evaluated and compared. Our results indicated that not accounting for missing data in the analysis yielded unstable estimates in the regression analysis. Incorporating variance weights and/or subject-level imputation improved precision by >50%, compared to ignoring missing data. We recommend that these simple easy-to-implement statistical tools be used to improve analysis of accelerometer data. PMID- 27405329 TI - Differential Regulation of Human Paired Associative Stimulation-Induced and Theta Burst Stimulation-Induced Plasticity by L-type and T-type Ca2+ Channels. AB - Activity-dependent changes of postsynaptic Ca2+-concentration are influenced by a variety of different Ca2+-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca2+-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca2+-sources. PAS-induced facilitation of corticospinal excitability was blocked by NMDA-receptor blocker dextromethorphan (DXM) and L-type voltage gated Ca2+ channels (VGCC) blocker nimodipine (NDP), but turned into depression by T-type VGCC blocker ethosuximide (ESM). Although, surprisingly, static corticospinal excitability was increased by the combination of DXM and NDP, PAS-induced facilitation was blocked. TBS-induced facilitation of corticospinal excitability, which has previously been shown to be turned into depression by L-type VGCC blocker NDP (Wankerl K, Weise D, Gentner R, Rumpf J, Classen J. 2010. L-type voltage-gated Ca2+ channels: a single molecular switch for long-term potentiation/long-term depression-like plasticity and activity-dependent metaplasticity in humans. J Neurosci. 30(18):6197-6204.), was blocked, but not reverted, by T-type VGCC blocker ESM. The different patterns of Ca2+-channel modulation of PAS- and TBS-induced plasticity may point to an important role of backpropagating action potentials in PAS-induced plasticity, similar as in spike-timing dependent synaptic plasticity, and to a requirement of dendritic Ca2+-dependent spikes in TBS-induced plasticity. PMID- 27405330 TI - Pleiotropic Hes-1 Concomitant with its Differential Activation Mediates Neural Stem Cell Maintenance and Radial Glial Propensity in Developing Neocortex. AB - Notch signaling pathway and its downstream effector Hes-1 are well known for their role in cortical neurogenesis. Despite the canonical activation of Hes-1 in developing neocortex, recent advances have laid considerable emphasis on Notch/CBF1-independent Hes-1 (NIHes-1) expression with poor understanding of its existence and functional significance. Here, using reporter systems and in utero electroporation, we could qualitatively unravel the existence of NIHes-1 expressing neural stem cells from the cohort of dependent progenitors throughout the mouse neocortical development. Though Hes-1 expression is maintained in neural progenitor territory at all times, a simple shift from Notch-independent to -dependent state makes it pleiotropic as the former maintains the neural stem cells in a non-dividing/slow-dividing state, whereas the latter is very much required for maintenance and proliferation of radial glial cells. Therefore, our results provide an additional complexity in neural progenitor heterogeneity regarding differential Hes-1 expression in the germinal zone during neo-cortical development. PMID- 27405331 TI - Frontoparietal Functional Connectivity in the Common Marmoset. AB - In contrast to the well established macaque monkey, little is known about functional connectivity patterns of common marmoset monkey (Callithrix jacchus) that is poised to become the leading transgenic primate model. Here, we used resting-state ultra-high-field fMRI data collected from anesthetized marmosets and macaques along with awake human subjects, to examine and compare the brain's functional organization, with emphasis on the saccade system. Exploratory independent component analysis revealed eight resting-state networks in marmosets that greatly overlapped with corresponding macaque and human networks including a distributed frontoparietal network. Seed-region analyses of the superior colliculus (SC) showed homolog areas in macaques and marmosets. The marmoset SC displayed the strongest frontal functional connectivity with area 8aD at the border to area 6DR. Functional connectivity of this frontal region revealed a similar functional connectivity pattern as the frontal eye fields in macaques and humans. Furthermore, areas 8aD, 8aV, PG,TPO, TE2, and TE3 were identified as major hubs based on region-wise evaluation of betweeness centrality, suggesting that these cortical regions make up the functional core of the marmoset brain. The results support an evolutionarily preserved frontoparietal system and provide a starting point for invasive neurophysiological studies in the marmoset saccade and visual systems. PMID- 27405332 TI - Cognitive Reserve and Brain Maintenance: Orthogonal Concepts in Theory and Practice. AB - Cognitive Reserve and Brain Maintenance have traditionally been understood as complementary concepts: Brain Maintenance captures the processes underlying the structural preservation of the brain with age, and might be assessed relative to age-matched peers. Cognitive Reserve, on the other hand, refers to how cognitive processing can be performed regardless of how well brain structure has been maintained. Thus, Brain Maintenance concerns the "hardware," whereas Cognitive Reserve concerns "software," that is, brain functioning explained by factors beyond mere brain structure. We used structural brain data from 368 community dwelling adults, age 20-80, to derive measures of Brain Maintenance and Cognitive Reserve. We found that Brain Maintenance and Cognitive were uncorrelated such that values on one measure did not imply anything about the other measure. Further, both measures were positively correlated with verbal intelligence and education, hinting at formative influences of the latter to both measures. We performed extensive split-half simulations to check our derived measures' statistical robustness. Our approach enables the out-of-sample quantification of Brain Maintenance and Cognitive Reserve for single subjects on the basis of chronological age, neuropsychological performance and structural brain measures. Future work will investigate the prognostic power of these measures with regard to future cognitive status. PMID- 27405334 TI - Inhibition of Information Flow to the Default Mode Network During Self-Reference Versus Reference to Others. AB - The default mode network (DMN), a network centered around the cortical midline, shows deactivation during most cognitive tasks and pronounced resting-state connectivity, but is actively engaged in self-reference and social cognition. It is, however, yet unclear how information reaches the DMN during social cognitive processing. Here, we addressed this question using dynamic causal modeling (DCM) of functional magnetic resonance imaging (fMRI) data acquired during self reference (SR) and reference to others (OR). Both conditions engaged the left inferior frontal gyrus (LIFG), most likely reflecting semantic processing. Within the DMN, self-reference preferentially elicited rostral anterior cingulate and ventromedial prefrontal cortex (rACC/vmPFC) activity, whereas OR engaged posterior cingulate and precuneus (PCC/PreCun). DCM revealed that the regulation of information flow to the DMN was primarily inhibitory. Most prominently, SR elicited inhibited information flow from the LIFG to the PCC/PreCun, while OR was associated with suppression of the connectivity from the LIFG to the rACC/vmPFC. These results suggest that task-related DMN activation is enabled by inhibitory down-regulation of task-irrelevant information flow when switching from rest to stimulus-specific processing. PMID- 27405333 TI - Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo. AB - Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two photon Ca(2+) imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca(2+) signals to sensory stimulation. These sensory evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID- 27405335 TI - HP-beta-cyclodextrin as an inhibitor of amyloid-beta aggregation and toxicity. AB - Amyloid deposits of misfolded amyloid-beta protein (Abeta) on neuronal cells are a pathological hallmark of Alzheimer's disease (AD). Prevention of the abnormal Abeta aggregation has been considered as a promising therapeutic strategy for AD treatment. To prevent reinventing the wheel, we proposed to search the existing drug database for other diseases to identify potential Abeta inhibitors. Herein, we reported the inhibitory activity of HP-beta-cyclodextrin (HP-beta-CD), a well known sugar used in drug delivery, genetic vector, environmental protection and treatment of Niemann-Pick disease type C1 (NPC1), against Abeta1-42 aggregation and Abeta-induced toxicity, with the aim of adding a new function as a sugar based Abeta inhibitor. Experimental data showed that HP-beta-CD molecules were not only nontoxic to cells, but also greatly inhibited Abeta fibrillization and reduced Abeta-induced toxicity in a concentration-dependent manner. At an optimal molar ratio of Abeta : HP-beta-CD = 1 : 2, HP-beta-CD enabled the reduction of 60% of Abeta fibrils and increased the cell viability to 92%. Such concentration dependent inhibitor capacity of HP-beta-CD was likely attributed to several combined effects, including the enhancement of Abeta-HP-beta-CD interactions, prevention of structural transition of Abeta peptides towards beta-sheet structures, and reduction of self-aggregation of HP-beta-CD. In parallel, molecular simulations further revealed the atomic details of HP-beta-CD interacting with the Abeta oligomer, showing that HP-beta-CD had a high tendency to interact with hydrophobic residues of Abeta in two beta-strands and the N terminal tail. More importantly, we identified that the inner hydrophobic cavity of HP-beta-CD was a key active site for Abeta inhibition. Once the inner cavity of HP-beta-CD was blocked by a small hydrophobic molecule of ferulic acid, HP beta-CD completely lost its inhibition capacity against Abeta. Given the already established pharmaceutical functions of HP-beta-CD in drug delivery, our findings suggest that HP-beta-CD has great potential to be designed as a sugar-based Abeta inhibitor. PMID- 27405336 TI - High flow nasal cannula in children: a literature review. AB - High flow nasal cannula (HFNC) is a relatively new non-invasive ventilation therapy that seems to be well tolerated in children. Recently a marked increase in the use of HFNC has been seen both in paediatric and adult care settings. The aim of this study was to review the current knowledge of HFNC regarding mechanisms of action, safety, clinical effects and tolerance in children beyond the newborn period.We performed a systematic search of the databases PubMed, Medline, EMBASE and Cochrane up to 12th of May 2016. Twenty-six clinical studies including children on HFNC beyond the newborn period with various respiratory diseases hospitalised in an emergency department, paediatric intensive care unit or general ward were included. Five of these studies were interventional studies and 21 were observational studies. Thirteen studies included only children with bronchiolitis, while the other studies included children with various respiratory conditions. Studies including infants hospitalised in a neonatal ward, or adults over 18 years of age, as well as expert reviews, were not systematically evaluated, but discussed if appropriate.The available studies suggest that HFNC is a relatively safe, well-tolerated and feasible method for delivering oxygen to children with few adverse events having been reported. Different mechanisms including washout of nasopharyngeal dead space, increased pulmonary compliance and some degree of distending airway pressure may be responsible for the effect. A positive clinical effect on various respiratory parameters has been observed and studies suggest that HFNC may reduce the work of breathing. Studies including children beyond the newborn period have found that HFNC may reduce the need of continuous positive airway pressure (CPAP) and invasive ventilation, but these studies are observational and have a low level of evidence. There are no international guidelines regarding flow rates and the optimal maximal flow for HFNC is not known, but few studies have used a flow rate higher than 10 L/min for infants.Until more evidence from randomized studies is available, HFNC may be used as a supplementary form of respiratory support in children, but with a critical approach regarding effect and safety, particularly when operated outside of a paediatric intensive care unit. PMID- 27405337 TI - Randomized double blind clinical trial on the effect of oral alpha-cyclodextrin on serum lipids. AB - BACKGROUND: This single center, double-blinded, cross-over, placebo controlled clinical trial investigated the effect of oral alpha-cyclodextrin (alpha-CD), a soluble dietary fiber, on blood lipid and lipoprotein levels in healthy human subjects. alpha-CD, a cyclical polymer containing 6 glucose subunits, is currently sold as an over the counter food supplement and is also a common additive in many foods. alpha-CD forms a hydrophobic central cavity that binds lipids and has been shown in animal studies and in previous clinical trials to alter plasma lipid levels. METHODS: We screened for healthy subjects, males and females, between ages 18 to 75. Out of total 103 subjects interviewed, 75 subjects completed the study. Qualified individuals in each gender group were randomized into two groups in terms of which treatment arm they received first (placebo vs. alpha-CD, receiving 6 grams P.O. a day, for 12-14 weeks with a 7 day wash out between arms). The primary outcome variable, plasma total cholesterol, as well as other tests related to lipids and lipoprotein and glucose metabolism, were measured at baseline and at the end of each arm of the study. RESULTS: alpha CD was well tolerated; no serious adverse events related to alpha-CD were observed. Approximately 8 % of the subjects on alpha-CD complained of minor gastrointestinal symptoms versus 3 % on placebo (p = 0.2). Small-LDL particle number decreased 10 % (p < 0.045) for subjects on alpha-CD versus placebo. Fasting plasma glucose (1.6 %, p < 0.05) and Insulin resistance index (11 %, p < 0.04) were also decreased when on alpha-CD versus placebo. CONCLUSION: alpha-CD treatment appears to be safe and well tolerated in healthy individuals and showed a modest reduction in small LDL particles, and an improvement in glucose related parameters. TRIAL REGISTRATION: NCT01131299. PMID- 27405339 TI - The laboratory comparison of shear bond strength and microscopic assessment of failure modes for a glass-ionomer cement and dentin bonding systems combined with silver nanoparticles. AB - PURPOSE: More than half of the cavity restorations are replaced due to bacterial microleakage. A need for disinfection agents arises. Application of silver nanoparticles (AgNPs) may be beneficial, yet their impact on the adhesives' shear bond strength to dentin remains unknown. METHODS: The aim was to assess the shear bond strength to dentin of different dental materials combined with AgNPs. Failure modes were also examined using SEM/FIB, SEM/EDS and endodontic microscopes. RESULTS: The results showed no impact of AgNPs addition to dental materials in terms of shear bond strength to dentin. A change of the failure mode of the self-etch bonding system, Clearfil SE Bond, combined with AgNPs was observed. The new failure modes depended upon the order of application of the materials onto dentin. CONCLUSIONS: The microscopic evaluation of the samples showed the presence of AgNPs agglomerations gathered on the dentin's surface. AgNPs connection with self-etching dentin bonding system may have a serious clinical impact. PMID- 27405340 TI - The impact of maternal hyper-oxygenation on foeto-placental blood flow. AB - OBJECTIVE: Maternal hyperoxygenation has been reported to increase foetal oxygen saturation, and is frequently employed during intra-partum episodes of foetal compromise as a component of in utero resuscitation. However, there has been little investigation of its influence on foetal haemodynamics, particularly in appropriately grown foetuses. METHODS: This cohort study was undertaken between July 2013 and November 2013. All participants underwent an ultrasound scan prior to active labour (<4 cm dilated), during which foetal biometry, umbilical and middle cerebral artery Dopplers were recorded. Doppler measurements were then repeated after a 20-min period (to act as a control for subsequent measurements after oxygen therapy). Women were then asked to breathe 60% oxygen through Venturi valve masks for 20 min, after which the Doppler measurements were repeated. RESULTS: Twenty women were recruited to the study. No significant change in the foetal cerebro-umbilical (CU) ratio was observed following maternal oxygen therapy. The degree of change in Doppler parameters after oxygen therapy was not related to the baseline value of the Doppler parameter. CONCLUSION: Maternal hyperoxygenation using 60% oxygen concentration over a 20-min period does not influence foetal umbilical or middle cerebral artery Doppler in appropriately grown foetuses. No adverse effects of maternal oxygen therapy were observed. PMID- 27405342 TI - Understanding the pelvic pain mechanism is key to find an adequate therapeutic approach. AB - Pain is a natural mechanism to actual or potential tissue damage and involves both a sensory and an emotional experience. In chronic pelvic pain, localisation of pain can be widespread and can cause considerable distress. A multidisciplinary approach is needed in order to fully understand the pelvic pain mechanism and to identify an adequate therapeutic approach. PMID- 27405338 TI - Sexual behaviour of women in rural South Africa: a descriptive study. AB - BACKGROUND: Sexual behaviour is a core determinant of the HIV and sexually transmitted infection (STI) epidemics in women living in rural South Africa. Knowledge of sexual behaviour in these areas is limited, but constitutes essential information for a combination prevention approach of behavioural change and biomedical interventions. METHODS: This descriptive study was conducted in rural Mopani District, South Africa, as part of a larger study on STI. Women of reproductive age (18-49 years) who reported sexual activity were included regardless of the reason for visiting the facility. Questionnaires were administered to 570 women. We report sexual behaviour by age group, ethnic group and self-reported HIV status. RESULTS: Young women (<25 years) were more likely to visit bars, practice fellatio, have concurrent sexual partners and report a circumcised partner than older women (>34 years); there was no difference for condom use during last sex act (36 % overall). Sotho women were more likely to report concurrent sexual partners whereas Shangaan women reported more frequent intravaginal cleansing and vaginal scarring practice in our analysis. HIV infected women were older, had a higher number of lifetime sexual partners, reported more frequent condom use during the last sex act and were more likely to have a known HIV-infected partner than women without HIV infection; hormonal contraceptive use, fellatio, and a circumcised partner were less often reported. CONCLUSIONS: This study provides insight into women's sexual behaviour in a rural South African region. There are important differences in sexual behaviour by age group and ethnicity and HIV status; these should be taken into account when designing tailor-made prevention packages. PMID- 27405343 TI - Fighting urinary tract infections with antibiotic and non-antibiotic therapies. AB - Urinary tract infections (UTIs) place a considerable burden on the patient and are associated with substantial economic cost. Treatment of UTIs is mainly achieved using antibiotics, however, the rise in antibiotic resistance is concerning and the use of non-antimicrobial prophylaxis offers alternative treatment methods. PMID- 27405344 TI - Glycosaminoglycans: how much do we know about their role in the bladder? AB - The urothelium is a unique lining in the body providing a protective barrier against the penetration of toxic agents, urine, and bacteria. The glycosaminoglycan (GAG) layer consists of a thick mucus layer of glycoproteins and proteoglycans on the surface of the urothelial cells. Damage to the GAG layer disrupts its protective barrier function giving rise to increased permeability into the deep layers of the urothelium and bladder, causing inflammation and pain. Replenishment of the GAG layer appears to restore normal permeability allowing for urothelial layer recovery. PMID- 27405346 TI - State of the art in intravesical gags therapy: from infection prevention to pain control. PMID- 27405345 TI - New preclinical data - the case for Ialuril(r). AB - This article briefly summarises data published over the last decade which have investigated the concept that intravesical instillation of glycosaminoglycans (GAGs) hyaluronic acid and chondroitin sulfate is able to restore the GAG layer and provide a beneficial effect in protecting the bladder. In the second half of this article, pre-clinical studies which assess the effectiveness of intravesical instillation of Ialuril(r) after chemical or electromechanical damage to the rat bladder wall are described. PMID- 27405347 TI - Adsorption of Papain on solid substrates of different hydrophobicity. AB - Adsorption properties of protein Papain at the solid|liquid (0.1 M KCl) interfaces of different hydrophobicity [highly oriented pyrolytic graphite (HOPG), bare gold, CH3, OH, and COOH-terminated self-assembled monolayers on gold] were studied by a combined quartz crystal microbalance and atomic force microscopy techniques. It was found that Papain forms an incomplete monolayer at hydrophobic interfaces (HOPG and CH3-terminated substrate), whereas on more hydrophilic ones, a complete monolayer formation was always observed with either the onset of the formation of a second layer (bare gold substrate) or adsorption in a multilayer fashion, possibly a bilayer formation (OH-terminated substrate). The surface concentration and compact monolayer film thickness was much lower on the COOH-terminated substrate compared to other surfaces studied. This result was explained by partial dissociation of the interfacial COOH groups leading to additional electrostatic interactions between the positively charged protein domains and negatively charged carboxylate anions, as well as to local pH changes promoting protein denaturation. PMID- 27405348 TI - Influences on uptake of cancer screening in mental health service users: a qualitative study. AB - BACKGROUND: Cancers are a leading cause of death worldwide. People with mental illness are 30 % more likely to die from cancer than the general population. One reason for this may be low uptake of nationally offered cancer screening tests by people with mental illness. We aimed to identify barriers and facilitators for breast, cervical and bowel cancer screening uptake by people with mental illness in order to inform interventions to promote equal access. METHODS: The interview study was conducted in both urban and rural settings. The study was informed by the Theoretical Domains Framework, using framework analysis and triangulation across participant groups. Participants included 45 mental health service users (service users) eligible for cancer screening, 29 mental health professionals and 11 professionals involved in cancer screening. RESULTS: Themes emerging from the data that affected uptake included knowledge of screening programmes by both service users and healthcare providers; knowledge of, and attitudes towards, mental illness; health service-delivery factors; service users' beliefs and concerns about cancer screening, and practical issues. These are relevant to different stages of the screening process. Service users do not receive invitations to screening or cancer testing kits if they are admitted to hospital. They are not routinely invited for screening if they are not registered with a general practitioner (GP). Lack of integrated care means that mental health staff do not know if someone is overdue for a test and cancer screening is often not considered during health promotion. Barriers including information processing problems, the extent to which the screening process aggravates symptoms, poor staff client relationships and travel difficulties vary between individuals. Screening professionals are motivated to help, but may lack time or training to manage mental health needs. Reactive measures are available, but service users must request help which they may find difficult. CONCLUSIONS: There are specific barriers to cancer screening uptake for mental health service users that prevent equality of care. Interventions that can be personalised are needed at individual, policy and service-delivery levels. Primary and secondary care staff and policy-makers should work together to develop an integrated approach to cancer screening in this population. PMID- 27405349 TI - Microbiome and mental health in the modern environment. AB - A revolution in the understanding of the pathophysiology of mental illness combined with new knowledge about host/microbiome interactions and psychoneuroimmunology has opened an entirely new field of study, the "psychobiotics". The modern microbiome is quite changed compared to our ancestral one due to diet, antibiotic exposure, and other environmental factors, and these differences may well impact our brain health. The sheer complexity and scope of how diet, probiotics, prebiotics, and intertwined environmental variables could influence mental health are profound obstacles to an organized and useful study of the microbiome and psychiatric disease. However, the potential for positive anti-inflammatory effects and symptom amelioration with perhaps few side effects makes the goal of clarifying the role of the microbiota in mental health a vital one. PMID- 27405350 TI - Solid-state, ambient-operation thermally activated delayed fluorescence from flexible, non-toxic gold-nanocluster thin films: towards the development of biocompatible light-emitting devices. AB - Luminescent gold nanoclusters (AuNCs) with good biocompatibility have gained much attention in bio-photonics. In addition, they also exhibit a unique photo physical property, namely thermally activated delayed fluorescence (TADF), by which both singlet and triplet excitons can be harvested. The combination of their non-toxic material property and unique TADF behavior makes AuNCs biocompatible nano-emitters for bio-related light-emitting devices. Unfortunately, the TADF emission is quenched when colloidal AuNCs are transferred to solid states under ambient environment. Here, a facile, low-cost and effective method was used to generate efficient and stable TADF emissions from solid AuNCs under ambient environment using polyvinyl alcohol as a solid matrix. To unravel the underlying mechanism, temperature-dependent static and transient photoluminescence measurements were performed and we found that two factors are crucial for solid TADF emission: small energy splitting between singlet and triplet states and the stabilization of the triplet states. Solid TADF films were also deposited on the flexible plastic substrate with patterned structures, thus mitigating the waveguide-mode losses. In addition, we also demonstrated that warm white light can be generated based on a co-doped single emissive layer, consisting of non-toxic, solution-processed TADF AuNCs and fluorescent carbon dots under UV excitation. PMID- 27405351 TI - Inactivation of spores by electric arcs. AB - BACKGROUND: In the context of spore contamination involved in bio-terrorism and food preservation, the development of new techniques for spore inactivation is an important challenge. RESULTS: Here, a successful application of electric arc discharges resulting in spore death was reported. Two types of electric arcs were compared, different with respect to their durations. The discharges with 0.5 MUs duration induced a small inactivation area of 0.6 % of surface treated around their point of entry into the sample, while those with 20 MUs duration induced a much larger inactivation area from 7 to 55 % of surface treated roughly proportional to the number of discharges delivered. In particular, 50 discharges of 20 MUs duration induced inactivation in more than 55% of surface treated at an inactivation rate above 3.6 log10. CONCLUSIONS: These results are promising and warrant developing electric arcing as a novel method for spore inactivation. PMID- 27405352 TI - Communicating prognostic uncertainty in potential end-of-life contexts: experiences of family members. AB - BACKGROUND: This article reports on the concept of "communicating prognostic uncertainty" which emerged from a mixed methods survey asking family members to rank their satisfaction in seven domains of hospital end-of-life care. METHODS: Open-ended questions were embedded within a previously validated survey asking family members about satisfaction with end-of-life care. The purpose was to understand, in the participants' own words, the connection between their numerical rankings of satisfaction and the experience of care. RESULTS: Our study found that nearly half of all family members wanted more information about possible outcomes of care, including knowledge that the patient was "sick enough to die". Prognostic uncertainty was often poorly communicated, if at all. Inappropriate techniques included information being cloaked in confusing euphemisms, providing unwanted false hope, and incongruence between message and the aggressive level of care being provided. In extreme cases, these techniques left a legacy of uncertainty and suspicion. Family members expressed an awareness of both the challenges and benefits of communicating prognostic uncertainty. Most importantly, respondents who acknowledged that they would have resisted (or did) knowing that the patient was sick enough to die also expressed a retrospective understanding that they would have liked, and benefitted, from more prognostic information that death was a possible or probable outcome of the patient's admission. Family members who reported discussion of prognostic uncertainty also reported high levels of effective communication and satisfaction with care. They also reported long-term benefits of knowing the patient was sick enough to die. CONCLUSION: While a patient who is sick enough to die may survive to discharge, foretelling with family members in potential end of life contexts facilitates the development of a shared and desired prognostic awareness that the patient is nearing end of life. PMID- 27405353 TI - Effectiveness of a cervical pessary for women who did not deliver 48 h after threatened preterm labor (Assessment of perinatal outcome after specific treatment in early labor: Apostel VI trial). AB - BACKGROUND: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor. METHODS/DESIGN: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, alpha 0.05 and beta 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat. DISCUSSION: The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth. TRIAL REGISTRATION: Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013. PMID- 27405354 TI - Physician staffed helicopter emergency medical service case identification - a before and after study in children. AB - BACKGROUND: Severely injured children may have better outcomes when transported directly to a Paediatric Trauma Centre (PTC). A case identification system using the crew of a physician staffed helicopter emergency medical service (P-HEMS) that identified severely injured children for P-HEMS dispatch was previously associated with high rates of direct transfer. It was theorised that discontinuation of this system may have resulted in deterioration of system performance. METHODS: Severe paediatric trauma cases were identified from a state based trauma registry over two time periods. In Period A the P-HEMS case identification system operated in parallel with a paramedic dispatcher (Rapid Launch Trauma Co-ordinator-RLTC) operating from a central control room (n = 71). In Period B the paramedic dispatcher operated in isolation (n = 126). Case identification and direct transfer rates were compared as was time to arrival at the PTC. RESULTS: After cessation of the P-HEMS system the rate of case identification fell from 62 to 31 % (P < 0.001), identification of fatal cases fell from 100 to 47 % (P < 0.001), the rate of direct transfer to a PTC fell from 66 to 53 % (P = 0.076) and the time to arrival in a PTC increased from a median 69 (interquartile range 52 - 104) mins to 97 (interquartile range 56 - 305) mins (P = 0.003). When analysing the rate of direct transfer to a PTC as a function of team composition, after adjusting for age and injury severity scores, there was no change in the rate between the physician and paramedic groups across the two time periods (relative risk 0.92, 95 % CI: 0.44 to 1.41). DISCUSSION: The parallel identification system improves case identification rates and decreases time to arrival at the PTC, whilst requiring RLTC authorisation preserves the safety and efficiency benefits of centralised dispatch. The model could be extended to adult patients with similar benefits. CONCLUSIONS: A case identification system relying solely on RLTC paramedics resulted in a significantly lower case identification rate and increased prehospital time with a non-significant fall in direct transfer rate to the PTC. The elimination of the P-HEMS input from the tasking system resulted in worse performance indicators and has the potential for poorer outcomes. PMID- 27405355 TI - Nerve excitation using an amplitude-modulated signal with kilohertz-frequency carrier and non-zero offset. AB - BACKGROUND: Incorporating kilohertz-frequency signals in transcutaneous electrical stimulation has been proposed as a means to overcome the impedance of the skin, thereby reaching deeper nerves. In particular, a transdermal amplitude modulated signal (TAMS), composed of a 210 kHz non-zero offset carrier modulated by rectangular pulses, was introduced recently for the treatment of overactive bladder. However, the contribution of the components of TAMS to nerve fiber activation has not been quantified. METHODS: We conducted in vivo experiments and applied direct stimulation to the sciatic nerve of cats and rats. We measured electromyogram and compound action potential activity evoked by pulses, TAMS and modified versions of TAMS in which we varied the size of the carrier. RESULTS: Nerve fiber activation using TAMS showed no difference with respect to activation with conventional pulse for carrier frequencies of 20 kHz and higher, regardless the relative amplitude of the carrier. For frequencies lower than 20 kHz, the offset needed to generate half of the maximal evoked response decreased significantly with respect to the pulse. Results of simulations in a computational model of nerve fiber stimulation using the same stimulation waveforms closely matched our experimental measurements. CONCLUSION: Taken together, these results suggest that a TAMS with carrier frequencies >20 kHz does not offer any advantage over conventional pulses, even with larger amplitudes of the carrier, and this has implications for design of waveforms for efficient and effective transcutaneous stimulation. PMID- 27405356 TI - Sub-wavelength Unidirectional Antenna Realized by Stacked Spoof Localized Surface Plasmon Resonators. AB - The use of resonant structures to control scattering strength and directionality is of importance in various electromagnetic systems. Here we propose and demonstrate sub-wavelength unidirectional scattering by two nearby spoof localized surface plasmon resonators for microwave. The principle is that metal surfaces corrugated by grooves can support magnetic dipolar modes, as well as electric dipolar modes. The resonance is essentially dictated by the geometric parameter of the structure, enabling extremely high degrees of freedom for tuning the scattering properties of the resonator. Particularly, by adjusting the thickness of the resonators, we can make the magnetic dipole mode of one resonator have nearly the same resonant frequency with that of the electric dipole mode of the other resonator. We show that nearly zero backscattering happens when the distance between the two resonators is subwavelenght but larger than a certain value, otherwise strong vertical coupling and mode splitting occur. The results can be extended to other frequency bands and might find application in unique resonant devices as a radio frequency (RF) antenna, filter and metasurface. PMID- 27405357 TI - Prevalence and familial predictors of suicidal behaviour among adolescents in Lithuania: a cross-sectional survey 2014. AB - BACKGROUND: In the past decades Lithuania has been experiencing a very high suicide rate among young people and there are scarce data on the role of the family in shaping these people suicidal behaviour. This study investigated the prevalence of suicidal ideation and attempts, as well as their association with a range of familial factors in a representative sample of Lithuanian adolescents. METHODS: Study subjects (N = 3572) were adolescents aged 13- and 15-years from the schools in Lithuania who were surveyed in Spring 2014 according to the methodology of the cross-national Health Behaviour in School-aged Children (HBSC). A standard HBSC international questionnaire was translated into Lithuanian and used anonymously to obtain information about suicidal behaviour (stopped doing activities, considered suicide, planned suicide, and suicide attempts) and family life (family structure, quality of communication in family, parental monitoring and bonding, parenting style, family time, etc.). Logistic regression was used to assess association between suicidal behaviours and familial variables. RESULTS: Forty three percents of surveyed adolescents reported presence of emotions that stopped doing activities during the last 12 months, 23.8 % seriously considered attempting suicide, 13.7 % made a suicide plan, 13.2 % attempted suicide, and 4.1 % needed treatment because of suicide attempt in the previous year. Adolescents from non-intact families reported more suicidal ideation (OR ranged from 1.32 to 1.35, P < 0.05) and more suicide attempts (OR = 1.70, 95 % CI 1.38-2.09, P < 0.001). Among adolescents from intact families, some manisfestations of suicidal behaviour were significantly associated with low satisfaction in family relationships, low father's and mother's emotional support, low mother's monitoring, low school-related parental support, authoritarian-repressive father's parenting style and permissive neglectful mother's parenting style, but rare family time together and rare electronic media communication with parents were inversely associated with suicidal behaviour. The boys, 15-year-olds and adolescents who indicated often activities together with their families were more likely than their counterparts to report suicide attempts treated by a doctor or nurse. CONCLUSION: The young people of Lithuania are at particular risk for suicides. A non-intact family structure and weak family functioning are significant predictors of suicidal ideation and attempts among adolescents of Lithuania. It is essential to consider family life practices in planning intervention programs for prevention of suicides among adolescents. PMID- 27405358 TI - Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia. AB - Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18-24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 MUg/mL) exhibited a better inhibiting effect on biofilm formation than 100 MUg/mL (P < 0.01), but with no difference in effect compared to the 50 MUg/mL concentration (P > 0.05). However, the inhibitory effects of 10 MUg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 MUg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID- 27405359 TI - Optimal control analysis of Ebola disease with control strategies of quarantine and vaccination. AB - BACKGROUND: The 2014 Ebola epidemic is the largest in history, affecting multiple countries in West Africa. Some isolated cases were also observed in other regions of the world. METHOD: In this paper, we introduce a deterministic SEIR type model with additional hospitalization, quarantine and vaccination components in order to understand the disease dynamics. Optimal control strategies, both in the case of hospitalization (with and without quarantine) and vaccination are used to predict the possible future outcome in terms of resource utilization for disease control and the effectiveness of vaccination on sick populations. Further, with the help of uncertainty and sensitivity analysis we also have identified the most sensitive parameters which effectively contribute to change the disease dynamics. We have performed mathematical analysis with numerical simulations and optimal control strategies on Ebola virus models. RESULTS: We used dynamical system tools with numerical simulations and optimal control strategies on our Ebola virus models. The original model, which allowed transmission of Ebola virus via human contact, was extended to include imperfect vaccination and quarantine. After the qualitative analysis of all three forms of Ebola model, numerical techniques, using MATLAB as a platform, were formulated and analyzed in detail. Our simulation results support the claims made in the qualitative section. CONCLUSION: Our model incorporates an important component of individuals with high risk level with exposure to disease, such as front line health care workers, family members of EVD patients and Individuals involved in burial of deceased EVD patients, rather than the general population in the affected areas. Our analysis suggests that in order for R 0 (i.e., the basic reproduction number) to be less than one, which is the basic requirement for the disease elimination, the transmission rate of isolated individuals should be less than one-fourth of that for non-isolated ones. Our analysis also predicts, we need high levels of medication and hospitalization at the beginning of an epidemic. Further, optimal control analysis of the model suggests the control strategies that may be adopted by public health authorities in order to reduce the impact of epidemics like Ebola. PMID- 27405360 TI - A versatile hard-soft N/S-ligand for metal coordination and cluster formation. AB - Deprotonation of the thialdiphosphazane [S[double bond, length as m-dash]PH(MU N(t)Bu)]2 with a range of metal-bases gives the stable dianion [S-P(MU N(t)Bu)]2(2-), which is valence-isoelectronic with the widely-used [RN-P(MU NR)]2(2-) ligand. Structural studies show that the new ligand has adaptable hard soft character with respect to the coordinated metal centre and that its multidentate nature can be exploited to construct large cage architectures. PMID- 27405361 TI - Estimates of Ethanol Exposure in Children from Food not Labeled as Alcohol Containing. AB - Ethanol is widely used in herbal medicines, e.g., for children. Furthermore, alcohol is a constituent of fermented food such as bread or yogurt and "non fermented" food such as fruit juices. At the same time, exposure to very low levels of ethanol in children is discussed as possibly having adverse effects on psychomotoric functions. Here, we have analyzed alcohol levels in different food products from the German market. It was found that orange, apple and grape juice contain substantial amounts of ethanol (up to 0.77 g/L). Furthermore, certain packed bakery products such as burger rolls or sweet milk rolls contained more than 1.2 g ethanol/100 g. We designed a scenario for average ethanol exposure by a 6-year-old child. Consumption data for the "categories" bananas, bread and bakery products and apple juice were derived from US and German surveys. An average daily exposure of 10.3 mg ethanol/kg body weight (b.w.) was estimated. If a high (acute) consumption level was assumed for one of the "categories," exposure rose to 12.5-23.3 mg/kg b.w. This amount is almost 2-fold (average) or up to 4-fold (high) higher than the lowest exposure from herbal medicines (6 mg/kg b.w.) suggested to require warning hints for the use in children. PMID- 27405362 TI - Fatal Combination with 3-Methylmethcathinone (3-MMC) and Gamma-Hydroxybutyric Acid (GHB). AB - We reported the case of 69-year-old man who was discovered dead at a friend's home. 3-Methylmethcathinone (3-MMC) and poppers (alkyl nitrites) were found at the scene by the police. Autopsy specimens including peripheral and cardiac blood, urine, gastric content, bile and hair were sent to our laboratory to document a possible death involving abuse of drugs. Routine toxicological analysis was performed with gas chromatography with flame ionization detection (GC-FID), high performance liquid chromatography-diode array detection (HPLC DAD), headspace gas chromatography-mass spectrometry (HS-GC-MS), gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)-MS. After liquid-liquid extraction at alkaline pH, 3-MMC was identified with GC-MS (to allow the discrimination with 4-MMC) and quantified with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-MS with the two following transitions: m/z 178.1 > 160 and 178.1 > 144.9. Gamma hydroxybutyric acid (GHB) was analyzed by GC-MS for fluids and GC-MS-MS for hair. Toxicological analysis in peripheral blood revealed the presence of 3-MMC (0.33 mg/L), pseudoephedrine (0.03 mg/L) and GHB (576 mg/L). These molecules have also been found in other post-mortem fluids. Furthermore, testing for "poppers" by HS GC-MS was negative. Hair analysis, without segmentation, demonstrated the presence of 3-MMC (206.7 ng/mg), pseudoephedrine (0.16 ng/mg) and GHB (96.3 ng/mg) and suggested a repeated consumption of these substances. However, one cannot exclude contamination by sweat during the agony period. Toxicological post mortem results suggest a fatal combination of 3-MMC and GHB. Despite his age, the decedent was known to abuse drugs. PMID- 27405363 TI - Case Report of Methylone, Oxymorphone and Ethanol in a Fatality Case with Tissue Distribution. AB - It is reasonable to expect the presence of multiple drugs to present a complicated picture of toxicity. We report a fatal case involving a young man who purchased illicit drugs and knowingly consumed them. After consuming these drugs and going to sleep in his friend's car, he was found unresponsive the next morning with no signs of physical violence. Drugs found in the peripheral blood at autopsy were oxymorphone, methylone and ethanol at concentrations of 0.106, 0.50 and 130 mg/dL, respectively. The levels of oxymorphone and methylone in peripheral blood were comparable to those observed in other reported fatalities. Cocaine and benzoylecgonine were detected in the urine but not in the blood. Measureable concentrations were also observed for oxymorphone and methylone in urine, liver, kidney and bile. The physical findings at autopsy included pulmonary edema. This is the only reported fatal case involving this combination of drugs encountered in our laboratory. PMID- 27405364 TI - ELISA Detection of 30 New Amphetamine Designer Drugs in Whole Blood, Urine and Oral Fluid using Neogen(r) "Amphetamine" and "Methamphetamine/MDMA" Kits. AB - Amphetamine designer drugs are central nervous system stimulants that are widely disseminated in the illegal market. Generally, in forensic laboratories, immunoassay methods are the first line of screening for these types of drugs in a biological specimen (typically blood, urine or oral fluid). In this article, we describe the cross-reactivity profiles of 30 new amphetamine designer drugs, using the Neogen((r)) [Amphetamine Specific and Methamphetamine/3,4 Methylenedioxymethamphetamine (MDMA) assays] drug tests. To assess the potential matrix influence on the response, each assay was tested on whole blood, urine and oral fluid. Concentrations of 10,000 ng/mL were not sufficient to produce a positive response for the majority of the analyzed amphetamines. This clearly demonstrates that, although these kits are extremely effective for the target drugs for which they are intended (amphetamine, methamphetamine and MDMA), they cannot be used to reliably identify the tested designer drugs in real cases, as these concentrations greatly exceed those expected to be found in forensic samples. PMID- 27405365 TI - Normalizing Oral Fluid Hydrocodone Data Using Calculated Blood Volume. AB - Oral fluid testing to assist in the assessment of treatment adherence for chronic pain patients is attractive for a number of reasons. However, efforts focused on interpreting patient results have been modest when compared to urine drug testing. This work details a retrospective approach developed to transform and normalize oral fluid testing results to provide a historical picture of patient values in this important test fluid. Using this approach, a model was developed using data from 6,800 independent patients who were both prescribed hydrocodone and tested positive (with limitations: reporting cutoff < X < upper limit of quantitation) by liquid chromatography-mass spectrometry. Patient demographic data were used to calculate the relevant parameters (e.g., calculated blood volume (CBV)) used in the transformation and normalization of the oral fluid data. The crucial normalizing factor in oral fluids was found to be the CBV which parallels the use of creatinine to normalize drug concentration levels in urine and is consistent with the view that oral fluid samples reflect plasma concentrations of the respective drugs. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from oral fluid testing. PMID- 27405366 TI - Variations in enzymatic hydrolysis efficiencies for amitriptyline and cyclobenzaprine in urine. AB - A collaborative study was conducted to investigate discrepancies in recoveries of two commonly prescribed compounds, amitriptyline and cyclobenzaprine, in patient urine samples when hydrolyzed with different enzymes from different sources. A 2- to 10-fold increase in analyte recoveries was seen for patient samples hydrolyzed using a recombinant beta-glucuronidase (IMCSzymeTM) over samples hydrolyzed with beta-glucuronidase from Haliotis rufescens We report outcomes from four commercially available beta-glucuronidase enzymes (IMCSzymeTM, Patella vulgata, Helix pomatia and H. rufescens) on patient samples that tested positive for amitriptyline and cyclobenzaprine. Our results confirm reduced hydrolysis of glucuronides by beta-glucuronidases isolated from mollusks, but near complete conversion when using the recombinant enzyme. Our premise is that systematic differences in hydrolysis efficiencies due to varying substrate affinity among enzyme subtypes potentially impacts accuracy and reliability of measurements. PMID- 27405367 TI - Reporting Two Fatalities Associated with the Use of 4-Methylethcathinone (4-MEC) and a Review of the Literature. AB - We report two fatalities that are related to the cathinone 4-methylethcathinone (4-MEC) and review the current knowledge of 4-MEC. Qualitative and quantitative analysis of 4-MEC was performed by validated high performance liquid chromatography-tandem mass spectrometry methods. In the first case a 22-year-old male died in hospital following collapse and seizures after using 4-MEC. Toxicological analysis of postmortem femoral blood revealed the presence of 4-MEC (0.167 mg/L), ethanol (27 mg/100 mL) and paracetamol (5 mg/L). Death was attributed solely to 4-MEC toxicity. The second case involved a 54-year-old man found with a taped plastic bag over his head. Toxicological analysis of postmortem femoral blood revealed the presence of 4-MEC (1.73 mg/L) along with ethanol (229 mg/100 mL), propranolol (0.036 mg/L), venlafaxine (0.284 mg/L) and its metabolite O-desmethylvenlafaxine (0.205 mg/L), and diazepam (<0.005 mg/L) and its metabolite nordiazepam (0.033 mg/L). Death was attributed primarily to asphyxiation. These cases and a review of the current knowledge of 4-MEC pharmacology/toxicology adds to the body of case material for 4-MEC and will assist with interpretation in postmortem toxicology cases in which 4-MEC is detected. PMID- 27405368 TI - Prescription Opioids. VI. Metabolism and Excretion of Hydromorphone in Urine Following Controlled Single-Dose Administration. AB - Hydromorphone (HM), a prescription opioid and metabolite of morphine and hydrocodone, has been included in proposed revisions to the Mandatory Guidelines for Federal Workplace Drug Testing Programs. This study characterized the time course of HM in hydrolyzed and non-hydrolyzed urine specimens. Twelve healthy subjects were administered a single 8 mg controlled-release HM dose, followed by periodic collection of pooled urine specimens for 54 h following administration. Analysis of total and free HM was conducted by liquid chromatography tandem mass spectrometry at a 50 ng/mL limit of quantitation. Detection periods were determined over a range of thresholds from 50 to 2,000 ng/mL. HM was detected in 85.3% and 47.6% of hydrolyzed and non-hydrolyzed post-dose specimens, respectively. Initial detection of total HM was frequently observed in the first 4-6 h following dosing. The period of detection at the 50 ng/mL threshold averaged 52.3 h for total HM and 38.0 h for free HM. These data support that HM detection is optimized by using low thresholds (50-100 ng/mL) and including conjugated HM in the analysis. PMID- 27405369 TI - Fentanyl-Norfentanyl Concentrations During Transdermal Patch Application: LC-MS MS Urine Analysis. AB - Poklis and Backer published a survey of the concentrations of fentanyl and norfentanyl that could be expected in urine from patients using Duragesic(r), a transdermal fentanyl patch. That study employed a relatively small number of patient data points and analysis by Gas Chromatography/Mass Spectrometry. This work examines a larger population of patient positives for fentanyl and norfentanyl to determine whether more than a decade later the original report remains accurate in predicting the range and median levels of fentanyl and norfentanyl concentrations physicians can expect to see from their patients. Additionally, these data were transformed to develop a model that results in a near Gaussian distribution of urine drug test results. This retrospective approach was developed to transform and normalize urine drug testing results to provide a historical picture of expected patient values for this important analgesic. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from urine drug testing. PMID- 27405370 TI - Prescription Opioids. V. Metabolism and Excretion of Oxymorphone in Urine Following Controlled Single Dose Administration. AB - Oxymorphone (OM), a prescription opioid and metabolite of oxycodone, was included in the recently published proposed revisions to the Mandatory Guidelines for Federal Workplace Drug Testing Programs. To facilitate toxicological interpretation, this study characterized the time course of OM and its metabolite, noroxymorphone (NOM), in hydrolyzed and non-hydrolyzed urine specimens. Twelve healthy subjects were administered a single 10 mg controlled release OM dose, followed by a periodic collection of pooled urine specimens for 54 h following administration. Analysis for free and total OM and NOM was conducted by liquid chromatography tandem mass spectrometry (LC-MS-MS), at a 50 ng/mL limit of quantitation (LOQ). Following enzymatic hydrolysis, OM and NOM were detected in 89.9% and 13.5% specimens, respectively. Without hydrolysis, OM was detected in 8.1% specimens, and NOM was not detected. The mean ratio of hydrolyzed OM to NOM was 41.6. OM was frequently detected in the first pooled collection 0-2 h post-dose, appearing at a mean of 2.4 h. NOM appeared at a mean of 8.3 h. The period of detection at the 50 ng/mL threshold averaged 50.7 h for OM and 11.0 h for NOM. These data support that OM analysis conducted using a 50 ng/mL threshold should include hydrolysis or optimize sensitivity for conjugated OM. PMID- 27405371 TI - Functional and regulatory conservation of the soybean ER stress-induced DCD/NRP mediated cell death signaling in plants. AB - BACKGROUND: The developmental and cell death domain (DCD)-containing asparagine rich proteins (NRPs) were first identified in soybean (Glycine max) as transducers of a cell death signal derived from prolonged endoplasmic reticulum (ER) stress, osmotic stress, drought or developmentally-programmed leaf senescence via the GmNAC81/GmNAC30/GmVPE signaling module. In spite of the relevance of the DCD/NRP-mediated signaling as a versatile adaptive response to multiple stresses, mechanistic knowledge of the pathway is lacking and the extent to which this pathway may operate in the plant kingdom has not been investigated. RESULTS: Here, we demonstrated that the DCD/NRP-mediated signaling also propagates a stress-induced cell death signal in other plant species with features of a programmed cell death (PCD) response. In silico analysis revealed that several plant genomes harbor conserved sequences of the pathway components, which share functional analogy with their soybean counterparts. We showed that GmNRPs, GmNAC81and VPE orthologs from Arabidopsis, designated as AtNRP-1, AtNRP 2, ANAC036 and gVPE, respectively, induced cell death when transiently expressed in N. benthamiana leaves. In addition, loss of AtNRP1 and AtNRP2 function attenuated ER stress-induced cell death in Arabidopsis, which was in marked contrast with the enhanced cell death phenotype displayed by overexpressing lines as compared to Col-0. Furthermore, atnrp-1 knockout mutants displayed enhanced sensitivity to PEG-induced osmotic stress, a phenotype that could be complemented with ectopic expression of either GmNRP-A or GmNRP-B. In addition, AtNRPs, ANAC036 and gVPE were induced by osmotic and ER stress to an extent that was modulated by the ER-resident molecular chaperone binding protein (BiP) similarly as in soybean. Finally, as putative downstream components of the NRP-mediated cell death signaling, the stress induction of AtNRP2, ANAC036 and gVPE was dependent on the AtNRP1 function. BiP overexpression also conferred tolerance to water stress in Arabidopsis, most likely due to modulation of the drought-induced NRP-mediated cell death response. CONCLUSION: Our results indicated that the NRP mediated cell death signaling operates in the plant kingdom with conserved regulatory mechanisms and hence may be target for engineering stress tolerance and adaptation in crops. PMID- 27405372 TI - Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials. AB - Plant-based dietary interventions have been proposed to reduce obesity induced chronic low-grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta-analysis of intervention trials aimed to assess the effect of plant-based diets on obesity related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta-analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant-based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, -0.55 mg/l, 95% confidence intervals (CI): -0.78; -0.32, I2 = 94.4%], IL-6 [effect size, -0.25 ng/l, 95% CI: -0.56; 0.06, I2 = 74%], and, to some degree, sICAM (-25.07 ng/ml [95% CI: -52.32; 2.17, I2 = 93.2%]). No substantial effects were revealed for TNF-alpha, resistin, adiponectin and leptin. Plant-based diets are associated with an improvement in obesity-related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk. PMID- 27405373 TI - Photoswitchable CuMoIV and CuMoIV cyanido-bridged molecules. AB - The self-assembly of copper(ii) complexes with two Schiff base ligands: L1O = N3 and L2 = N4 and octacyanidomolybdate(iv) ions yields two discrete molecules of odd nuclearity, namely pentametallic [Cu(L1O)(py)]4[MoIV(CN)8].14H2O (1), Cu4Mo and trimetallic [Cu(L2)]2[MoIV(CN)8].9H2O (2), Cu2Mo. Both molecular systems have been characterised structurally and magnetically, revealing a photomagnetic effect. In the case of (1) a metal-to-metal charge transfer (MMCT) mechanism is proposed. The analysis of magnetic interactions in the photogenerated state of (1) assumes the formation of the metastable cluster CuCuIMoV where metal centres in MoV-CN-CuII linkages are ferromagnetically coupled with J2 = 104(3) cm-1. In (2) the increase in the magnetisation is due to the singlet-triplet transition on the MoIV centre leading to the formation of the metastable CuMo. The presence of the paramagnetic Mo (S = 1) centre linking the CuII (S = 1/2) centres allows for effective ferromagnetic interaction of 3 paramagnetic centres with coupling constant J2 = 20.2(7) cm-1. PMID- 27405374 TI - Contraceptive method choice among women in slum and non-slum communities in Nairobi, Kenya. AB - BACKGROUND: Understanding women's contraceptive method choices is key to enhancing family planning services provision and programming. Currently however, very little research has addressed inter and intra-regional disparities in women's contraceptive method choice. Using data from slum and non-slum contexts in Nairobi, Kenya, the current study investigates the prevalence of and factors associated with contraceptive method choice among women. METHODS: Data were from a cross-sectional quantitative study conducted among a random sample of 1,873 women (aged 15-49 years) in two non-slum and two slum settlement areas in Nairobi, Kenya. The study locations were purposively sampled by virtue of being part of the Nairobi Urban Health and Demographic Surveillance System. Bivariate and multivariate logistic regression were used to explore the association between the outcome variable, contraceptive method choice, and explanatory variables. RESULTS: The prevalence of contraceptive method choice was relatively similar across slum and non-slum settlements. 34.3 % of women in slum communities and 28.1 % of women in non-slum communities reported using short-term methods. Slightly more women living in the non-slum settlements reported use of long-term methods, 9.2 %, compared to 3.6 % in slum communities. Older women were less likely to use short-term methods than their younger counterparts but more likely to use long-term methods. Currently married women were more likely than never married women to use short-term and long-term methods. Compared to those with no children, women with three or more children were more likely to report using long term methods. Women working outside the home or those in formal employment also used modern methods of contraception more than those in self-employment or unemployed. CONCLUSION: Use of short-term and long-term methods is generally low among women living in slum and non-slum contexts in Nairobi. Investments in increasing women's access to various contraceptive options are urgently needed to help increase contraceptive prevalence rate. Thus, interventions that focus on more disadvantaged segments of the population will accelerate contraceptive uptake and improve maternal and child health in Kenya. PMID- 27405375 TI - Preparedness of health care professionals in preventing maternal mortality at a public health facility in Ghana: a qualitative study. AB - BACKGROUND: Preparedness of health care professionals for emergency situations is quite indispensable in quality health care; yet, information barely exists on the preparedness of health care professionals for emergency cases in health facilities in Ghana. This study sought to assess the preparedness of health professionals in preventing maternal mortality cases at a public health facility in Ghana. METHODS: This is a qualitative study that used purposive and convenient sampling techniques to recruit 12 health care professionals for in-depth interviews. The interviews were tape-recorded, transcribed and the results presented in themes verbatim. RESULTS: The results show that health care professionals at the hospital were ill-equipped to effectively handle maternal mortality cases in the municipality. As such, inadequate staff size and dearth of essential logistics militate against the preparedness of health care professionals in curbing maternal mortality. CONCLUSIONS: More health care professionals and essential logistics should, therefore, be provided by the Ghana Health Service to augment the existing ones. PMID- 27405376 TI - Interactions between warming and soil moisture increase overlap in reproductive phenology among species in an alpine meadow. AB - Climate warming strongly influences reproductive phenology of plants in alpine and Arctic ecosystems. Here, we focus on phenological shifts caused by experimental warming in a typical alpine meadow on the Tibetan Plateau. Under soil water stress caused by warming, most plants in the alpine meadow advanced or delayed their reproductive events to be aligned with the timing of peak rainfall. As a result, warming significantly increased the temporal overlap among reproductive stages of early- and late-flowering species. In addition, we found that some species, for example the late-flowering species, were unable to produce flowers and fruits under warming with failed monsoon rains. The potentially warmer- and drier-growing seasons under climate change may similarly shift the phenological patterns and change species composition of these alpine systems. PMID- 27405377 TI - Ageing and the cost of maintaining coloration in the Australian painted dragon. AB - There is now good evidence in several taxa that animal coloration positively reflects an individual's antioxidant capacity. However, even though telomeres, a marker of ageing, are known to be vulnerable to reactive oxygen species (ROS) attacks, no studies have ever assessed whether colour fading reflects the rate of biological ageing in any taxa. Here, we measured colour fading, telomere erosion (a measure of biological ageing) and ROS levels in painted dragons. We show that individuals that were better at maintaining their coloration during the three months of the study suffered a higher cost in terms of telomere erosion, but overall ROS levels measured at the start of the study were not significantly related to colour maintenance and telomere shortening. We therefore suggest that colour maintenance is a costly phenomenon in terms of telomere erosion, and that overall ROS levels do not seem to be a crucial component linking ornamental coloration and telomere erosion in our study system. PMID- 27405378 TI - Novel shell device for gas exchange in an operculate land snail. AB - The operculum of terrestrial snails tightly seals the shell aperture providing protection from predators and body-water loss. To allow respiration with a closed operculum, operculate land snails repeatedly evolved shell devices such as tubes or channels that open to the air. In all Asian members of the Alycaeidae, an externally closed tube lies along the suture behind the aperture that possesses a small internal opening into the last whorl at the tube's anterior end. However, this structure presents a paradox: how is gas exchanged through an externally closed tube? Here we show that many microtunnels open into the tube and run beneath radial ribs along the growth line of the last whorl in Alycaeus conformis These tunnels open to the outside of the shell surface near the umbilicus. Examination under high magnification revealed that the outermost shell layer forms these tunnels only in the whorl range beneath the sutural tube. Each tunnel (ca 16 um diameter) is far narrower than any known metazoan parasite. These findings support our hypothesis that the externally closed sutural tube functions with microtunnels as a specialized apparatus for predator-free gas exchange with minimal water loss when the operculum seals the aperture. PMID- 27405379 TI - Song discrimination by nestling collared flycatchers during early development. AB - Pre-zygotic isolation is often maintained by species-specific signals and preferences. However, in species where signals are learnt, as in songbirds, learning errors can lead to costly hybridization. Song discrimination expressed during early developmental stages may ensure selective learning later in life but can be difficult to demonstrate before behavioural responses are obvious. Here, we use a novel method, measuring changes in metabolic rate, to detect song perception and discrimination in collared flycatcher embryos and nestlings. We found that nestlings as early as 7 days old respond to song with increased metabolic rate, and, by 9 days old, have increased metabolic rate when listening to conspecific when compared with heterospecific song. This early discrimination between songs probably leads to fewer heterospecific matings, and thus higher fitness of collared flycatchers living in sympatry with closely related species. PMID- 27405380 TI - Topology, divergence dates, and macroevolutionary inferences vary between different tip-dating approaches applied to fossil theropods (Dinosauria). AB - Dated phylogenies of fossil taxa allow palaeobiologists to estimate the timing of major divergences and placement of extinct lineages, and to test macroevolutionary hypotheses. Recently developed Bayesian 'tip-dating' methods simultaneously infer and date the branching relationships among fossil taxa, and infer putative ancestral relationships. Using a previously published dataset for extinct theropod dinosaurs, we contrast the dated relationships inferred by several tip-dating approaches and evaluate potential downstream effects on phylogenetic comparative methods. We also compare tip-dating analyses to maximum parsimony trees time-scaled via alternative a posteriori approaches including via the probabilistic cal3 method. Among tip-dating analyses, we find opposing but strongly supported relationships, despite similarity in inferred ancestors. Overall, tip-dating methods infer divergence dates often millions (or tens of millions) of years older than the earliest stratigraphic appearance of that clade. Model-comparison analyses of the pattern of body-size evolution found that the support for evolutionary mode can vary across and between tree samples from cal3 and tip-dating approaches. These differences suggest that model and software choice in dating analyses can have a substantial impact on the dated phylogenies obtained and broader evolutionary inferences. PMID- 27405381 TI - Costly learning: preference for familiar food persists despite negative impact on survival. AB - Animals often rely on events in their environment that provide information (i.e. experience) to alter their future decision-making in ways that are presumed to be beneficial. Such experience-based learning, however, does not always lead to adaptive decision-making. In this study, we use the omnivorous harvestman Heteromitobates discolor to explore the role of past diet on subsequent food choice and survival. We first tested whether a short-term homogeneous diet (rotten crickets, fresh crickets or dog food) influenced subsequent food choice (rotten cricket versus fresh cricket). We next examine the impact of diet on survival. We found that following experience with a homogeneous cricket diet, adult harvestmen displayed a learned preference for familiar food, regardless of whether it was rotten or fresh crickets; individuals experiencing dog food were equally likely to choose rotten versus fresh crickets. We additionally found that individuals that ate rotten crickets suffered shorter survival than those that ate fresh crickets. Together, our results suggest that the diet an individual experiences can lead to maladaptive food preferences-preferences that ultimately result in reduced longevity. PMID- 27405382 TI - Developmental plasticity evolved according to specialist-generalist trade-offs in experimental populations of Drosophila melanogaster. AB - We studied the evolution of developmental plasticity in populations of Drosophila melanogaster that evolved at either constant or fluctuating temperatures. Consistent with theory, genotypes that evolved at a constant 16 degrees C or 25 degrees C performed best when raised and tested at that temperature. Genotypes that evolved at fluctuating temperatures performed well at either temperature, but only when raised and tested at the same temperature. Our results confirm evolutionary patterns predicted by theory, including a loss of plasticity and a benefit of specialization in constant environments. PMID- 27405383 TI - Bees use the taste of pollen to determine which flowers to visit. AB - Pollen plays a dual role as both a gametophyte and a nutritional reward for pollinators. Although pollen chemistry varies across plant species, its functional significance in pollination has remained obscure, in part because little is known about how floral visitors assess it. Bees rely on pollen for protein, but whether foragers evaluate its chemistry is unclear, as it is primarily consumed by larvae. We asked whether the chemical composition of pollen influences bumblebees' foraging behaviour. Using putatively sweet and bitter pollen blends, we found that chemical composition influenced two aspects of bee behaviour relevant to plant fitness: the amount of pollen collected and the likelihood of subsequently visiting a visually similar flower. These findings offer a new perspective on the nutritional ecology of plant-pollinator interactions, as they show that pollen's taste may mediate its collection and transfer. PMID- 27405384 TI - One size fits all? Direct evidence for the heterogeneity of genetic drift throughout the genome. AB - Effective population size (Ne) is a central parameter in population and conservation genetics. It measures the magnitude of genetic drift, rates of accumulation of inbreeding in a population, and it conditions the efficacy of selection. It is often assumed that a single Ne can account for the evolution of genomes. However, recent work provides indirect evidence for heterogeneity in Ne throughout the genome. We study this by examining genome-wide diversity in the Danish Holstein cattle breed. Using the differences in allele frequencies over a single generation, we directly estimated Ne among autosomes and smaller windows within autosomes. We found statistically significant variation in Ne at both scales. However, no correlation was found between the detected regional variability in Ne, and proxies for the intensity of linked selection (local recombination rate, gene density), or the presence of either past strong selection or current artificial selection on traits of economic value. Our findings call for further caution regarding the wide applicability of the Ne concept for understanding quantitatively processes such as genetic drift and accumulation of consanguinity in both natural and managed populations. PMID- 27405385 TI - Taking stock. PMID- 27405386 TI - Achieving Consensus for the Design and Delivery of an Online Intervention to Support Midwives in Work-Related Psychological Distress: Results From a Delphi Study. AB - BACKGROUND: Some midwives are known to experience both professional and organizational sources of psychological distress, which can manifest as a result of the emotionally demanding midwifery work, and the traumatic work environments they endure. An online intervention may be one option midwives may engage with in pursuit of effective support. However, the priorities for the development of an online intervention to effectively support midwives in work-related psychological distress have yet to be explored. OBJECTIVE: The aim of this study was to explore priorities in the development of an online intervention to support midwives in work-related psychological distress. METHODS: A two-round online Delphi study was conducted. This study invited both qualitative and quantitative data from experts recruited via a scoping literature search and social media channels. RESULTS: In total, 185 experts were invited to participate in this Delphi study. Of all participants invited to contribute, 35.7% (66/185) completed Round 1 and of those who participated in this first round, 67% (44/66) continued to complete Round 2. Out of 39 questions posed over two rounds, 18 statements (46%) achieved consensus, 21 (54%) did not. Participants were given the opportunity to write any additional comments as free text. In total, 1604 free text responses were collected and categorized into 2446 separate statements of opinion, creating a total of 442 themes. Overall, participants agreed that in order to effectively support midwives in work-related psychological distress, online interventions should make confidentiality and anonymity a high priority, along with 24-hour mobile access, effective moderation, an online discussion forum, and additional legal, educational, and therapeutic components. It was also agreed that midwives should be offered a simple user assessment to identify those people deemed to be at risk of either causing harm to others or experiencing harm themselves, and direct them to appropriate support. CONCLUSIONS: This study has identified priorities for the development of online interventions to effectively support midwives in work-related psychological distress. The impact of any future intervention of this type will be optimized by utilizing these findings in the development process. PMID- 27405387 TI - 17.6%-Efficient radial junction solar cells using silicon nano/micro hybrid structures. AB - We developed a unique nano- and microwire hybrid structure by selectively modifying only the tops of microwires using metal-assisted chemical etching. The proposed nano/micro hybrid structure not only minimizes surface recombination but also absorbs 97% of incident light under AM 1.5G illumination, demonstrating outstanding light absorption compared to that of planar (59%) and microwire arrays (85%). The proposed hybrid solar cells with an area of 1 cm(2) exhibit power conversion efficiencies (Eff) of up to 17.6% under AM 1.5G illumination. In particular, the solar cells show a high short-circuit current density (Jsc) of 39.5 mA cm(-2) because of the high light-absorbing characteristics of the nanostructures. This corresponds to an approximately 61.5% and 16.5% increase in efficiency compared to that of a planar silicon solar cell (Eff = 10.9%) and a microwire solar cell (Eff = 15.1%), respectively. Therefore, we expect the proposed hybrid structure to become a foundational technology for the development of highly efficient radial junction solar cells. PMID- 27405388 TI - High-Throughput Nanoliter-Scale Analysis and Optimization of Multimodal Chromatography for the Capture of Monoclonal Antibodies. AB - Multimodal ligands are synthetic molecules comprising multiple types of interactions that have been increasingly used for the capture of different biopharmaceutical compounds within complex biological mixtures. For monoclonal antibodies (mAbs) in particular, these ligands have shown the possibility of direct capture from cell culture supernatants in native conditions, as well as enhanced selectivity and affinity compared to traditional single-mode ligands. However, performing the capture of a target mAb using multimodal chromatography comes with the need for extensive optimization of the operating conditions, due to the multitude of interactions that can be promoted in parallel. In this work, a high-throughput microfluidic platform was developed for the optimization of chromatographic conditions regarding the capture of an anti-interleukin 8 mAb, using a multimodal ligand (2-benzamido-4-mercaptobutanoic acid), under a wide range of buffer pH and conductivities. The interaction of the ligand with the fluorescently labeled target mAb was also analyzed with respect to the individual contribution of the hydrophobic (phenyl) and electrostatic (carboxyl) moieties using fluorescence microscopy. The results were further validated at the macroscale using prepacked columns in standard chromatography assays, and recovery yield values of 94.6% +/- 5.2% and 97.7% +/- 1.5% were obtained under optimal conditions for the miniaturized and conventional approaches, respectively. In summary, this study highlights that a microfluidic-based approach is a powerful analytical tool to expedite the optimization process while using reduced reagent volumes (<50 MUL), less resin (~70 nL), and delivering results in less than 1 min per assay condition. PMID- 27405389 TI - Erratum to: The use of balloons for uterine cervical ripening is associated with an increased risk of umbilical cord prolapse: population based questionnaire survey in Japan. PMID- 27405390 TI - The efficacy and safety of rituximab in treating childhood nephrotic syndrome: an Italian perspective. AB - BACKGROUND: Nephrotic syndrome is a disorder characterized by proteinuria, hypoalbuminemia and dyslipidemia. Low-dose alternate-day steroid regimen is the standard of care. In case of relapse or significant adverse events, steroid sparing agents may be used. This analysis was aimed at assessing the efficacy and safety of rituximab for the treatment of children with nephrotic syndrome. RESULTS: Four studies were included in the final meta-analysis. The end-point of our analysis was the percentage of patients in remission at 6 months. Pooled data from the four studies favours the use of rituximab (RR 5.25, 95 % CI: 3.05-9.06; p < 0.0001). As regards the safety data, rituximab has a limited number of adverse effects, the most common of which occur during the infusions. CONCLUSIONS: In Italy, the off-label use of drugs is regulated by Law 648/96. In our opinion, there are three scientific requirements to merit a conditional national reimbursement for rituximab in nephrotic syndrome: 1. favourable clinical efficacy and safety data; 2. no available alternatives; 3. outcome data collecting by AIFA through prescribers. In conclusion, our results report a significant incremental benefit of adding rituximab to corticosteroid and/or calcineurin inhibitors for the treatment of nephrotic syndrome. PMID- 27405391 TI - Distinctive polymer micelle designed for siRNA delivery and reversal of MDR1 gene dependent multidrug resistance. AB - P-glycoprotein (P-gp) plays an importantrole in multidrug resistance (MDR), proved to be one of the major obstacles in cancer chemotherapy. Cationic polymers could specifically deliver siRNA to tumor cells and thus reverse MDR by the downregulation of P-gp. In this study, a triblock copolymer micelle was prepared based on the polymer of N-succinyl-chitosan-poly-l-lysine-palmitic acid (NSC-PLL PA) to deliver siRNA-P-gp (siRNA-micelle) or doxorubicin (Dox-micelle). The resulting micelle exhibited an efficient binding ability for siRNA and high encapsulation efficiency for Dox, with an average particle size of ~170 nm. siRNA micelle and Dox-micellewere instable at low pH, thereby enhancing tumor accumulation and intracellular release of the encapsulated siRNA and Dox. siRNA micelle micelles could enhance the knockdown efficacy of siRNA by improving the transfection efficiency, downregulating P-gp expression, and passing the drug efflux transporters, thereby improving the therapeutic effects of Dox-micelle. However, P-gp could transfer from HepG2/ADM to HepG2 cells independent of the expression of mdr1, and the acquired resistance could permit tumor cells to survive and develop intrinsic P-gp-mediated resistance, thereby limiting the desired efficiency of chemotherapeutics. This study demonstrated the effectiveness of siRNA-micelle for tumor-targeted delivery, MDR reversal, and provided an effective strategy for the treatment of cancers that develop MDR. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2093 2106, 2017. PMID- 27405392 TI - G45R mutation in the nonstructural protein 1 of A/Puerto Rico/8/1934 (H1N1) enhances viral replication independent of dsRNA-binding activity and type I interferon biology. AB - BACKGROUND: The nonstructural protein 1 (NS1) of influenza A viruses can act as a viral replication enhancer by antagonizing type I interferon (IFN) induction and response in infected cells. We previously reported that A/Puerto Rico/8/1934 (H1N1) (PR8) containing the NS1 gene derived from A/swine/IA/15/1930 (H1N1) (IA30) replicated more efficiently than the wild type virus. Here, we identified amino acids in NS1 critical for enhancing viral replication. METHODS: To identify a key amino acid in NS1 which can increase the virus replication, growth kinetics of PR8 viruses encoding single mutation in NS1 were compared in A549 cells. NS1 mutant functions were studied using dsRNA-protein pull down, RIG-I mediated IFNbeta-promoter activity assays and growth curve analysis in murine lung epithelial type I (Let1) cells. RESULTS: The G45R mutation in the NS1 of PR8 (G45R/NS1) virus is critical for the enhanced viral replication in A549 cells. G45R/NS1 slightly decreased NS1 binding to dsRNA but did not interfere with its suppression of RIG-I-mediated type I IFN production. Likewise, replication of G45R/NS1 virus was increased in comparison to wild type virus in both wild type and type I interferon receptor null Let1 cells. CONCLUSIONS: The non-conserved amino acid, R45, enhances viral replication which is apparently independent of dsRNA binding and suppression of type I IFN, suggesting a non-characterized function of NS1 for the enhanced viral replication. As G45R/NS1 virus induced the type I IFN induction and response in infected A549 cells, it is also interesting to investigate virus virulence for further studies. PMID- 27405394 TI - Serum pharmacokinetics of choline, trimethylamine, and trimethylamine-N-oxide after oral gavage of phosphatidylcholines with different fatty acid compositions in mice. AB - Little is known about the pharmacokinetics of phosphatidylcholine (PC)-derived choline, trimethylamine (TMA), and trimethylamine-N-oxide (TMAO). We therefore aim to investigate serum choline, TMA, and TMAO pharmacokinetics following different PCs gavage and compare the difference between PC emulsions and liposomes (SOL). Serum choline, TMA, and TMAO levels were measured after orally gavaged egg yolk PC emulsion (EGE), squid PC emulsion (SQE), soybean PC emulsion (SOE), and SOL in fasted mice. Time to reach peak concentration (Tmax) and productions for TMA and TMAO were more slow and less in SQE group compared with EGE and SOE groups. Tmax for choline, TMA, and TMAO prolonged, and the productions of them were significantly declined in SOL group compared to SOE group. These findings indicated that marine source squid PC could counter regulate the potential risks of TMAO generation, and the use of liposome as the form of PC supplementary may eliminate TMAO production. PMID- 27405393 TI - Complete Genome Analysis of an Enterovirus EV-B83 Isolated in China. AB - Enterovirus B83 (EV-B83) is a recently identified member of enterovirus species B. It is a rarely reported serotype and up to date, only the complete genome sequence of the prototype strain from the United States is available. In this study, we describe the complete genomic characterization of an EV-B83 strain 246/YN/CHN/08HC isolated from a healthy child living in border region of Yunnan Province, China in 2008. Compared with the prototype strain, it had 79.6% similarity in the complete genome and 78.9% similarity in the VP1 coding region, reflecting the great genetic divergence among them. VP1-coding region alignment revealed it had 77.2-91.3% with other EV-B83 sequences available in GenBank. Similarity plot analysis revealed it had higher identity with several other EV-B serotypes than the EV-B83 prototype strain in the P2 and P3 coding region, suggesting multiple recombination events might have occurred. The great genetic divergence with previously isolated strains and the extremely rare isolation suggest this serotype has circulated at a low epidemic strength for many years. This is the first report of complete genome of EV-B83 in China. PMID- 27405395 TI - Membrane Stress During Thawing Elicits Redistribution of Aquaporin 7 But Not of Aquaporin 9 in Boar Spermatozoa. AB - Freezing of boar spermatozoa includes the cryoprotectant glycerol, but renders low cryosurvival, owing to major changes in osmolarity during freezing/thawing. We hypothesize that aquaporins (AQPs) 7 and 9 adapt their membrane domain location to these osmotic challenges, thus maintaining sperm homeostasis. Western blotting (WB) and immunocytochemistry (ICC) at light and electron microscope levels with several commercial primary antibodies and protocols explored AQP location on cauda epididymal and ejaculated spermatozoa (from different fractions of the ejaculate), unprocessed, extended, chilled and frozen-thawed. Although differences in WB and ICC labelling were seen among antibodies, AQP-7 was conspicuously located in the entire tail and cytoplasmic droplet in caudal spermatozoa, being restricted to the mid-piece and principal piece domains in ejaculated spermatozoa. AQP-9 was mainly localized in the sperm head in both caudal and ejaculated spermatozoa. While unaffected by chilling (+5 degrees C), freezing and thawing of ejaculated spermatozoa clearly relocated the head labelling of AQP-7, but not that of AQP-9. In vitro mimicking of cell membrane expansion during quick thawing maintained the localization of AQP-9 but relocated AQP-7 towards the acrosome. AQP-7, but not AQP-9, appears as a relevant marker for non-empirical studies of sperm handling. PMID- 27405397 TI - The fracture behaviors of monolayer phosphorene with grain boundaries under tension: a molecular dynamics study. AB - The fracture behaviors of monolayer phosphorene (MP) with and without a grain boundary (GB) have been explored by molecular dynamics (MD) simulations. Firstly, in the case of perfect MP, fracture mostly happens on the bond in the zigzag direction when suffering random loading. With the existence of a GB, the crack propagates perpendicular to the GB in different ways under parallel tension to the GB, whereas it propagates along the GB under perpendicular tension to the GB. Then, we found that both the fracture strength and strain decrease with increasing temperature making fracture more likely at relatively high temperatures. Finally, we also found that, similar to graphene, the effect of strain rate on both the fracture strength and strain is not significant, demonstrating that MP is a typical brittle 2D material. Overall, our findings present a useful insight into utilizing phosphorene for mechanical design in electronic devices. PMID- 27405396 TI - Effects of an exclusive breastfeeding intervention for six months on growth patterns of 4-5 year old children in Uganda: the cluster-randomised PROMISE EBF trial. AB - BACKGROUND: Breastfeeding promotion is regarded as one of the most effective interventions to improve child health, and could reduce under-5-mortality by 8 % globally. Few studies have assessed the health outcomes beyond infancy of interventions promoting exclusive breastfeeding. METHODS: This study assessed growth in under-five children who participated in a cluster-randomised trial in Eastern Uganda (ClinicalTrials.gov.no.NCT00397150). In the intervention arm, peer counsellors promoted exclusive breastfeeding during the first 6 months of infancy. There were no interventions after 6 months of age. Mother-infant pairs were interviewed at visits scheduled at 3, 6, 12 and 24 weeks after birth and follow-up visits at 2 and 5 years, with 765 included in the analyses. RESULTS: The mean length/height-for-age and weight-for-age-z-score (HAZ, WAZ) decreased with increasing age in both the intervention and control arms. At the three weeks visit, HAZ in the intervention was -0.45 (-0.68;-0.21) and -0.32 (-0.56;-0.07) in the control arm. At the 2 year follow-up, the mean HAZ in the intervention was 1.85 (95 % CI -1.97;-1.73) compared to -1.61 (-1.87;-1.34) in the control. Similarly, at the 5 year follow-up, the mean HAZ in the intervention was -1.78 ( 2.08;-1.47) compared to -1.53 (-1.79;-1.28) in the control arm. At the 2 year follow-up visit, 139 (45 %) were stunted (HAZ<-2) in the intervention compared to 109 (37 %) in the control arm, odds ratio (OR) 1.7 (1.1;2.4). Underweight (WAZ< 2) was also more common in the intervention arm than in the control at the five years follow-up (OR 1.7 (1.0;2.8)), with a mean WAZ of -1.28 (-1.47;-1.08) and 1.06 (-1.19;-0.92) in the intervention and control arm, respectively. CONCLUSION: While stunting was widespread at 2 and 5 years of age in both arms, it was more common in the intervention arm. It is questionable whether community-based support from lay people with short training and focussing only on exclusive breastfeeding, is an appropriate strategy to improve child health and development. TRIAL REGISTRATION: ClinicalTrials.gov.no. NCT00397150 . Registered 7th of November 2006. PMID- 27405398 TI - Synthesis and Evaluation of [(18) F]-Ammonium BODIPY Dyes as Potential Positron Emission Tomography Agents for Myocardial Perfusion Imaging. AB - Recently, we demonstrated the potential of a [(18) F]-trimethylammonium BODIPY dye for cardiac imaging. This is the first example of the use of the [(18) F] ammonium BODIPY dye for positron emission tomography (PET) myocardial perfusion imaging (MPI). In this report, we extend our study to other ammonium BODIPY dyes with different nitrogen substituents. These novel ammonium BODIPY dyes were successfully prepared and radiolabeled by the SnCl4 -assisted (18) F-(19) F isotopic exchange method. The microPET results and the biodistribution data reveal that nitrogen substituent changes have a significant effect on the in vivo and pharmacological properties of the tracers. Of the novel [(18) F]-ammonium BODIPY dyes prepared in this work, the [(18) F]-dimethylethylammonium BODIPY is superior in terms of myocardium uptake and PET imaging contrast. These results support our hypothesis that the ammonium BODIPY dyes have a great potential for use as PET/optical dual-modality MPI probes. PMID- 27405399 TI - The consumer-driven development and acceptability testing of a website designed to connect rural cancer patients and their families, carers and health professionals with appropriate information and psychosocial support. AB - Websites offer new opportunities to provide health-related information to rural communities. However, how acceptable they are to this population is unknown. This paper describes the consumer-led development of a website that provides rural specific information on psychosocial care for rural South Australians affected by cancer, and examines its acceptability to users. The Country Cancer Support website was developed with people affected by cancer living in rural South Australia (N = 11), using a Participatory Action Research Framework and evidence based behaviour change strategies. There were 32,389 visits in the first 3 years. An online survey (N = 111) revealed that users found the website easy to use, helpful and relevant. Most rural cancer patients and supporters (98.11%) believed it had been written by people who understood what they were going through. Patients and supporters for whom it was relevant, reported feeling more motivated and confident in accessing psychosocial support services in their rural area (66.67%) and/or capital city (67.65%) and/or in travelling for medical treatment (75.86%). Many also felt less isolated (73.33%) and/or distressed (53.57%). All health professionals reported gaining new knowledge. This study shows that carefully designed websites can successfully address rural populations' health information needs and increase intentions to access psychosocial support. PMID- 27405401 TI - Current Practice in the Treatment of Haemophilia. AB - Haematologists are long standing proponents of evidence based practice-well exemplified among professionals who care for patients with haemophilia. The rapidly expanding range of therapeutic products and the numerous accompanying clinical trials are swiftly interpreted and translated into clinical practice. This translation is formalised by frequently updated quidelines issued by the United Kingdom Haemophilia Centre Directors' Organisation (UKHCDO) and relevant to all doctors involved in the care of patients with haemophilia. In the last five years eight sets of guidelines have been issued in the UK alone relating to the treatment of haemophilia and its complications [1-8]. Against this background we aim to review current practice in the treatment of haemophilia. PMID- 27405400 TI - The association between nitroglycerin use and adverse outcomes in women undergoing cesarean delivery in the second stage of labor. AB - OBJECTIVE: To identify predictors of hysterotomy extension in women undergoing cesarean delivery (CD) in the second stage of labor, and whether use of nitroglycerin (NTG) during CD has a protective effect. METHODS: We conducted a retrospective cohort study of women undergoing CD in the second stage of labor from 2012 to 2015. Some women received NTG at the obstetrician's request. Logistic regression was used to examine the relationship between second stage duration and NTG administration on maternal and neonatal outcomes. RESULTS: Of the 391 women in the sample, 27% had an extension and 12% received NTG. Second stage >=4 h was associated with a 2.14-fold higher risk of extension (95% CI 1.22 3.75), a 2.00-fold higher risk of hemorrhage (95% CI: 1.20-3.33) and 2.42-fold higher risk of blood transfusion during delivery hospitalization (95% CI: 0.99 5.91). Intravenous (IV) and sublingual-spray (SL-spray) NTG administration were not associated with an increased risk of hemorrhage or extension. SL-NTG was associated with 4.68-fold increased odds of 5-min Apgar <7 (95% CI 1.42-15.41) and 3.36-fold greater odds of NICU admission (95% CI 1.20-9.41). CONCLUSION: We found no evidence that NTG protects against extension, and SL-NTG use was associated with adverse neonatal outcomes. Clinical trials should be conducted to evaluate risk and benefits of NTG use. PMID- 27405402 TI - Chromosome 7 and Haematological Malignancies. AB - Abnormalities of chromosome 7 are the most common clonal chromosomal changes observed in myelodysplasia (MDS) and the second most frequent in acute myeloid leukaemia (AML) [1-5]. These changes may consist of long arm deletion (7q-) or total loss of the whole chromosome (monosomy 7) from bone marrow cells [1, 4, 6 24] and was first reported in association with myeloid disease in 1964 with the report of 3 cases of refractory anaemia, granulocytic hyperplasia [25]. The association between chromosome 7 alterations, MDS and AML in children and adults is clear, however, a rare association with lymphoid malignancies has also been recently reported. The abnormalities may occur in de novo MDS/AML, secondary cases following exposure to drugs, radiotherapy and toxins and in addition in a range of constitutional disorders including Fanconi's anaemia, congenital neutropenia and neurofibromatosis type 1 (NF1). The broad spread of conditions in which this consistent genetic change can occur leads one to speculate that there is an underlying instability in chromosome 7 and that genes on this chromosome play a role in the development of malignancy. The loss of DNA associated with malignant progression suggests the presence of a tumour suppressor gene (or genes) [26, 27]. Patients with monosomy 7 usually present as classical MDS with abnormal erythroid, megakaryocyte and myeloid differentiation [7, 28]. From a mechanistic perspective, increased cell proliferation and apoptosis is a common feature possibly induced by the failure of normal haematopoietic maturation. In all groups the presence of chromosome 7 abnormalities defines a poor prognostic group [29]. The majority of patients with MDS transform to a form of acute leukaemia resistant to therapy, including bone marrow transplantation (BMT). Although fluorescence in situ hybridization (FISH) has accelerated the study of these disorders at the cytogenetic and molecular levels, [4, 30, 31, 32, 33] no gene has been clearly implicated. A few candidate genes are under investigation. While the loss of chromsome 7 material is crutial in the malignant process it is almost certainly not the primary molecular abnormality. An initiating event genetic event predisposing to chromosome breakage and loss probably occurs in haematopoietic cells permitting chromosome 7 loss and progression to clonal malignancy as a secondary event. PMID- 27405403 TI - Trisomy 12 is a Rare Event in Cases of CLL with Typical Immunophenotype and Morphology. AB - 131 patients with lymphoproliferative disorders were classified as having typical Chromic Lymphocytic Leukaemia [CLL], atypical CLL, Chromic Lymphocytic Leukaemia/Prolymphocytic Leukaemia [CLL/PL] or Non-Hodgkin's Lymphoma [NHL] using immunophenotyping and morphology. The incidence of trisomy 12 (+12) in each of the groups was ascertained using fluorescent in situ hybridization. Trisomy 12 was found to be rare in the typical CLL group (<3%) and more common in the atypical CLL (22%), CLL/PL (40%) and NHL (43%) categories. The low incidence of +12 in the typical CLL group is most likely due to our adherence to strict inclusion criteria to ensure other similar lymphoproliferative disorders, with a high incidence of +12, were excluded. This approach leads to more homogeneous disease categories and consequently may help to resolve issues such as the impact on survival of +12 in CLL. PMID- 27405404 TI - A Further Study on the Incidence of Nucleoli in Myeloblasts of Patients Suffering from Acute Myeloid Leukemia. AB - Nucleoli in bone marrow myeloblasts of patients suffering from acute myeloid leukemias (FAB M1-M4) untreated with cytostatics were investigated in smear preparations stained for RNA to provide the missing information on the incidence of main nucleolar types in these cells. Most myeloblasts possessed large nucleoli with a relatively uniform distribution of RNA which are known to be active with respect to the transcription of the nucleolar-ribosomal RNA. A small proportion of myeloblasts contained functionally dominant "resting" ring shaped nucleoli or "inactive" micronucleoli. The nucleolar asynchrony, i.e., the presence of "active large nucleoli" and "resting" ring shaped nucleoli in one and the same nucleus present in some myeloblasts of all investigated patients apparently represents a regular phenomenon in these cells. No significant differences were noted in the incidence of functionally dominant nucleoli between bone marrow and peripheral blood myeloblasts. On the other hand, the larger percentage of "active large nucleoli" in bone marrow myeloblasts and the increased percentage of "resting" ring shaped nucleoli in peripheral blood myeloblasts of the same patients may indicate a decreased transcription activity of nucleoli in the latter. No significant differences in the values of the nucleolar coefficient were found between bone marrow and peripheral blood myeloblasts. The presence of main nucleolar types in leukemic myeloblasts visualized by a simple but sensitive cytochemical procedure for the demonstration of RNA seems to be an useful tool for the evaluation of individual leukemic cells and provides an additional information on their biology. PMID- 27405405 TI - A Case of Malignant Histiocytosis having Polyploid Clones Characterized by an Isochromosome of the Long Arm of Chromosome 17 [i(17q)] and t(9;22) Translocation. AB - We report an interesting case of Malignant Histiocytosis (MH) with polyploid clones characterized by i(17q) and t(9; 22) translocation. A 47-year-old man had lymphadenopthy, splenomegaly and leukopenia at presentation. Bone marrow (BM) cytology showed 10.5% abnormal histiocytes. Karyotypic analyses with R- and G banding techniques on BM cells revealed complex abnormalities: 88, XXYY, add(2) (p25), -4, -8, -11, i(17q), -21[4]/89, idem, t(9; 22) (q34; q11), +22[26]/46, XY [47], of which, t(9; 22) was confirmed by fluorescence in situ hybridization using a chromosome 22 paint wcp 22+. This patient was treated with interferon alpha and COP regimen. 10 months later he achieved a complete hematologic and cytogenetic remission (CR). However, relapse occurred one year after achieving CR. At that time, cytogenetic examination showed a new polyploid clone characterized by add(1) (p36), add(2) (p25), -4, -8, t(9; 22), -11, i(17q), -21, +22 in addition to the other two polyploid clones observed previously. RT-PCR indicated that the BCR/ABL transcript (165bp) observed in classic chronic myeloid leukemia, was present, MH with t(9; 22) has not previously been described in the literature. This case may be the first one of MH with t(9; 22), and is likely a secondary event. PMID- 27405406 TI - A Long-term Remission of a Recurrent Acute Lymphoblastic Leukaemia with Donor Leukocyte Infusions after Allogeneic Peripheral Blood Stem Cell Transplantation. AB - This case report describes a patient with recurrent and refractory acute lymphoblastic leukaemia (ALL-L3), who relapsed four months after a HLA identical allogeneic Peripheral Blood Stem Cell (PBSC) transplantation; he was treated after relapse with intensive chemotherapy and then he received leukocyte infusion from her sibling donor. A long term Complete Remission (CR) was achieved, with complete chimerism and without signs of chronic GVHD. Thirteen months after Donor Leukocyte Infusion (DLI), he developed a relapse (4% blasts in BM), and a second infusion of leukocytes with the same chemotherapy schedule was performed. Six months after the second DLI the patient is alive. Since responses to Donor Lymphocyte Infusions (DLI) are uncommon in ALL, the possible causative factors for this unusual response are discussed. PMID- 27405407 TI - Molecular Pathogenesis of Paroxysmal Nocturnal Hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH), although named for its marked fluctuations in the visibility of hemoglobinuria, is now classified as an acquired hematopoietic stem cell disorder. The clinical manifestations of PNH are very complicated, and include intravascular hemolytic anemia, venous thrombosis in unusual sites (abdomen, liver, cerebrum), deficient hematopoiesis, evolution to leukemia, and susceptibility to infection [1, 2]. The intravascular hemolysis is attributed to the enhanced susceptibility of erythrocytes to autologous complement [3]. The abnormal sensitivity is explained by a lack of complement regulatory membrane proteins such as decay-accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), which are covalently linked to the erythrocyte membrane through a glycosylphosphatidylinositol (GPI) anchor. The deficiency of the membrane proteins is caused by a synthetic defect in this anchor caused by impaired transfer of N- acetylglucosamine (GlcNAc) to phosphatidylinositol (PIns) [2]. Mutations of the phosphatidylinositol glycan class A (PIG-A) gene have been shown to contribute this abnormality in nearly all patients with PNH studied to date [4]. Recently, several reviews have been presented on various aspects of PNH [5-10]. This review focuses particularly on the recent elucidation of the molecular pathogenesis of GPI-anchor deficiency on PNH and related hematopoietic stem cell disorders. PMID- 27405408 TI - G CSF: A First Line Therapy for Autoimmune Neutropenia? AB - This paper studies the use of recombinant human Granulocyte Colony Stimulating Factor (rh G CSF) as a single treatment modality in serologically proven autoimmune neutropenia. We present six cases, all of whom had severe neutropenia resulting in recurrent infections and oral ulceration. A response, characterised by an increase in mean neutrophil count and a reduction in infective episodes, was demonstrated in all cases. PMID- 27405409 TI - Acute Normovolemic Hemodilution in Surgery. AB - Acute normovolemic hemodilution (ANH) is a technique in which whole blood is removed from a patient while the circulating blood volume is maintained with acellular fluid shortly before a surgical procedure that is anticipated to result in significant blood loss. While this technique was studied and developed over 25 years ago [1], ANH is today seldom practiced and remains controversial [2,3], despite recommendation of its use by consensus statements such as an expert panel [4] of the National Heart, Lung, and Blood Institutes. The purpose of this review is to address recent advances in the understanding of this blood conservation stratergy, along with its emerging role in autologous blood procurement strategies. PMID- 27405410 TI - Has Lactoferrin a Role in Hereditary Hemochromatosis? PMID- 27405412 TI - Mechanical assessment of a hip joint stem model made of a PEEK/carbon fibre composite under compression loading. AB - PURPOSE: The aim of the work was to manufacture a composite stem model consisting of carbon fibres (CF) and polyether ether ketone (PEEK) and to perform the surface strain and stress distributions in the stem-femoral bone model under compression loading. METHODS: Composite stems differing in elasticity were prepared. Three types of composite stems having different arrangements of carbon fibre reinforcements (carbon fibre roving, carbon fibre sleeves and their combinations) in the polymer matrix were made. The stems were cementless fixed in the femoral bone model channel or with the use of the polymer bone cement (PMMA). Mechanical behaviour of composite stems under compression loading was compared with a metallic stem by strain gauge measurements at different parts of stem/bone model systems. RESULTS: The values of stresses in the proximal part of the bone model for cemented and cementless fixations of the composite stem in the femoral bone channel were higher than those noted for the metallic stem. The increase in proximal bone stress was almost similar for both types of fixation of composite stems, i.e., cemented and cementless fixed stems. CONCLUSIONS: The optimal range of mechanical stiffness, strengths and work up to fracture was obtained for composite stem made of carbon fibre sleeves and carbon fibres in the form of roving. Depending on the elasticity of the composite stem model, an increase in the stress in the proximal part of femoral bone model of up to 40% was achieved in comparison with the metallic stem. PMID- 27405413 TI - Gastro-oesophageal reflux associated with duodenum inversum: two case reports and a review of the literature. AB - Gastro-oesophageal reflux disease (GORD) is a very common paediatric disorder and the majority of patients are treated successfully by primary care physicians. Two infants aged 2 months with GORD which did not respond to conventional medical management are reported; they were diagnosed with duodenum inversum. The first infant failed medical management and required Nissen's fundoplication to control his symptoms. The second infant improved on maximizing medical management without the need for a surgical procedure. These two cases highlight the need for further work-up in patients who do not respond to conventional GORD therapy and/or present with atypical clinical symptoms. PMID- 27405411 TI - Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity. AB - Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain. Examination of simultaneous membrane interaction and triple-helix binding revealed a possible regulation of proteolysis due to steric effects of the membrane. At bicelle concentrations of 1%, enzymatic activity towards triple helices was increased 1.5-fold. A single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) resulted in lower enzyme activation by bicelles. An initial structural framework has thus been developed to define the role(s) of cell membranes in modulating proteolysis. PMID- 27405415 TI - Gene expression in term placentas is regulated more by spinal or epidural anesthesia than by late-onset preeclampsia or gestational diabetes mellitus. AB - Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are common complications of pregnancy, but the mechanisms underlying these disorders remain unclear. The aim was to identify the extent of altered gene expression in term placentas from pregnant women with late-onset PE and GDM compared to controls. RNAseq identified few significantly differentially regulated genes in placental biopsies between PE, GDM, or uncomplicated pregnancy (n = 10 each group). Five genes were altered in placentas from PE including 4 non-coding genes and Angiopoietin 2 (ANGPT2). No genes were significantly regulated by GDM. In contrast, many genes were significantly regulated by fetal, maternal and delivery specific variables, particularly spinal and epidural anesthesia. We selected ANGPT2 and Chemokine (C-X-C motif) ligand 14 (CXCL14) to test with qPCR in a larger set of placentas (n = 475) and found no differences between the groups. However, regression analysis revealed a stronger association between placental ANGPT2 and CXCL14 mRNA expression and fetal, maternal and delivery-specific variables than diagnostic group. To conclude, the gene expression in term placentas are highly affected by fetal, maternal and delivery specific variables. Few regulated genes were found in late-onset PE and GDM placentas, which may suggest that these conditions could be more affected by maternal factors. PMID- 27405417 TI - Pseudo-double T wave ECG artifact. AB - In the ECG of a diabetic patient without coronary artery disease, a double T wave was observed. The ECG was normal the next day. This finding was interpreted as representing repolarization abnormalities (e. g., myocardial ischemia) by many health care workers. However, it represents an artifact called "pseudo double T wave". The cause is unknown but most likely due to abnormalities at the interface between surface electrodes and skin tissue. The diagnosis of ECG artifacts requires meticulous examination of the tracings coupled with a thorough knowledge of normal patterns. PMID- 27405416 TI - Elevated CO2 can modify the response to a water status gradient in a steppe grass: from cell organelles to photosynthetic capacity to plant growth. AB - BACKGROUND: The atmospheric CO2 concentration is rising continuously, and abnormal precipitation may occur more frequently in the future. Although the effects of elevated CO2 and drought on plants have been well reported individually, little is known about their interaction, particularly over a water status gradient. Here, we aimed to characterize the effects of elevated CO2 and a water status gradient on the growth, photosynthetic capacity, and mesophyll cell ultrastructure of a dominant grass from a degraded grassland. RESULTS: Elevated CO2 stimulated plant biomass to a greater extent under moderate changes in water status than under either extreme drought or over-watering conditions. Photosynthetic capacity and stomatal conductance were also enhanced by elevated CO2 under moderate drought, but inhibited with over-watering. Severe drought distorted mesophyll cell organelles, but CO2 enrichment partly alleviated this effect. Intrinsic water use efficiency (WUEi) and total biomass water use efficiency (WUEt) were increased by elevated CO2, regardless of water status. Plant structural traits were also found to be tightly associated with photosynthetic potentials. CONCLUSION: The results indicated that CO2 enrichment alleviated severe and moderate drought stress, and highlighted that CO2 fertilization's dependency on water status should be considered when projecting key species' responses to climate change in dry ecosystems. PMID- 27405418 TI - Noise from a dysfunctional atrial lead detected as atrial fibrillation by a cardiac implantable electronic device. AB - A patient with a dual chamber implantable cardioverter-defibrillator developed a defective atrial lead whereupon the generated false atrial signals were repeatedly interpreted as atrial tachycardia/atrial fibrillation (AF) by the atrial upper rate algorithm coupled with rare episodes of noise reversion. This unusual response highlights the limitations of the upper atrial rate triggers of device diagnosis of supraventricular tachyarrhythmias. The converse may occur with a very fine AF or with a very sensitive sensitivity setting (e. g., 0.1 mV) when AF can be detected as noise. PMID- 27405419 TI - Comprehensive design of omnidirectional high-performance perovskite solar cells. AB - The comprehensive design approach is established with coupled optical-electrical simulation for perovskite-based solar cell, which emerged as one of the most promising competitors to silicon solar cell for its low-cost fabrication and high PCE. The selection of structured surface, effect of geometry parameters, incident angle-dependence and polarization-sensitivity are considered in the simulation. The optical modeling is performed via the finite-difference time-domain method whilst the electrical properties are obtained by solving the coupled nonlinear equations of Poisson, continuity, and drift-diffusion equations. The optical and electrical performances of five different structured surfaces are compared to select a best structured surface for perovskite solar cell. The effects of the geometry parameters on the optical and electrical properties of the perovskite cell are analyzed. The results indicate that the light harvesting is obviously enhanced by the structured surface. The electrical performance can be remarkably improved due to the enhanced light harvesting of the designed best structured surface. The angle-dependence for s- and p-polarizations is investigated. The structured surface exhibits omnidirectional behavior and favorable polarization insensitive feature within a wide incident angle range. Such a comprehensive design approach can highlight the potential of perovskite cell for power conversion in the full daylight. PMID- 27405420 TI - An investigation of the mediating role of personality and family functioning in the association between attachment styles and eating disorder status. AB - BACKGROUND: This study examined relationships between attachment style, eating disorders (EDs), personality variables and family functioning. METHODS: In our study, 253 women (M = 25.72 years, SD = 8.73) were grouped into one of four categories either according to self-reported ED diagnosis or by exceeding cut offs for a clinical diagnosis on the Eating Disorder Examination Questionnaire (EDE-Q) or Short Evaluation of Eating Disorders (SEED): anorexia nervosa (AN), bulimia nervosa (BN), other eating disorder (O-ED), no eating disorder (Non-ED). The ED group (AN, BN, O-ED) included 106 women (M = 24.74 years, SD = 7.71), and the Non-ED group 147 women (M = 26.42 years, SD = 9.37). Approximately half of the ED group had a comorbid disorder (59.4 %), while the majority of the Non-ED group had no psychological disorder (89.1 %). RESULTS: Participants with an ED were significantly more often insecurely attached (Adult Attachment Scale; AAS), emotionally unstable, less extraverted (Big-Five-Test of Personality; B5T) and showed less positive family functioning (Experiences in Personal Social Systems Questionnaire; EXIS.pers). Results showed partial mediation for attachment and EDs through neuroticism, extraversion and family functioning. DISCUSSION: The study found further evidence for elevated problems with attachment, personality, and family experiences in individuals with EDs, while suggesting mechanisms that may link these constructs. Implications for research and practice were discussed. CONCLUSION: This study supports findings that acknowledge the mediating role played by personality factors and family functioning in the relationship between attachment and EDs. PMID- 27405421 TI - Reliability and Validity of the Turkish Eating Assessment Tool (T-EAT-10). AB - The purpose of this study was to test the reliability and validity of the Turkish Eating Assessment Tool (T-EAT-10) among patients with swallowing disorders. One hundred and five patients completed the T-EAT-10 and Functional Oral Intake Scale (FOIS). The internal consistency, test-retest reliability, and criterion validity of T-EAT-10 were investigated. The internal consistency was assessed using Cronbach's alpha. Intraclass correlation coefficient (ICC) value with 95 % confidence intervals was calculated for test-retest reliability. The criterion validity of the T-EAT-10 was determined by assessing the correlation between T EAT-10 and FOIS. All the patients in the study completed the T-EAT-10 without assistance. The mean time to complete the instrument was 1.8 +/- 0.9 min. The internal consistency of the T-EAT-10 was found to be high with 0.90 Cronbach's alpha for test and 0.91 Cronbach's alpha for retest reproducibility. No difference between the test and retest scores of the T-EAT-10 was found (p = 0.14). A negative, moderate correlation between T-EAT-10 and FOIS was detected (r = -0.365, p < 0.001). The T-EAT-10 is a reliable and valid symptom-specific outcome tool for dysphagia in adult Turkish patients. It can be used in clinical practice and research. PMID- 27405422 TI - Clinical Characteristics of Dysphagia in Children with Down Syndrome. AB - Aspiration is an often unrecognized comorbidity in children with Down syndrome with serious medical consequences. This retrospective chart review of swallow study reports characterizes oral and pharyngeal phase dysphagia and diet modifications on videofluoroscopic swallow studies (VFSS) in a large cohort of children with Down syndrome. A total of 158 pediatric patients (male = 95; female = 63; mean age 2.10 years, SD 3.17 years) received an initial VFSS at a pediatric teaching hospital as part of their medical care. A total of 56.3 % (n = 89) children had pharyngeal phase dysphagia with aspiration and deep laryngeal penetration occurring most frequently. Of the 61 patients who aspirated, 90.2 % (n = 55) did so silently with no cough or overt clinical symptoms. In 76.7 % of cases of pharyngeal phase dysphagia, a functional feeding plan, with use of thickened liquids or change in feeding system to control flow rate and/or bolus size, was able to be established, which allowed children to continue eating by mouth. Thickened liquids (76.7 %, n = 46) were the most effective adaptation, with change in feeding system alone effective in only 8.3 % (n = 5) cases. Oral phase dysphagia was reported in the majority of patients (63.8 %, n = 88/138); however, this was not predictive of pharyngeal phase dysphagia. Age, sex, and reason for referral, including prior clinical symptoms, did not have a statistically significant impact on the presence of dysphagia. This comprehensive review has application to clinical understanding and management of dysphagia in children with Down syndrome. PMID- 27405423 TI - Implications of Variability in Clinical Bedside Swallowing Assessment Practices by Speech Language Pathologists. AB - Speech language pathology (SLP) clinical bedside swallowing assessments (CBSA) are a cornerstone of quality care for patients in acute hospitals who have dysphagia. The CBSA informs clinical diagnosis and decisions regarding further instrumental assessment, and is used to develop a management plan and monitor progress. However, self-report and retrospective research shows that SLPs are highly variable in their use of assessment components considered by experts to be important for quality CBSA, casting doubt on the validity and reliability of CBSA. This prospective study describes the components included by SLPs when designing a standardised evidence based dysphagia assessment protocol for acute care patients and observed patterns of component use. The findings confirm that SLPs use the CBSA for multiple purposes beyond diagnosis of aspiration risk and dysphagia presence/severity. They are highly variable in their use of certain components, but also demonstrate consistent use of a core set. It is apparent that SLPs prioritise the application of clinical reasoning to tailor their CBSA to the patient over following a highly structured item-based protocol. The variability in component use likely reflects a complex clinical reasoning process that draws on a wide variety of information combined with expert knowledge as is also observed in many other medical specialties. Rather than promoting the standardisation of CBSA protocols that constrain SLP practice to strict item based assessment protocols, consideration should be given to promoting the value and facilitating the clinical reasoning process that supports the utility of the CBSA for diagnosis, patient centred management and treatment planning. PMID- 27405424 TI - Solvothermal synthesis of nanoporous TiO2: the impact on thin-film composite membranes for engineered osmosis application. AB - In the current study, the impact of self-synthesized nanoporous titanium oxide (NT) on the morphology, performance and fouling of a polyamide (PA) thin-film composite (TFC) membrane was investigated when the membrane was applied for engineering osmosis (EO). The nanoporous structure and the spindle-like shape of NT were revealed through transmission electron microscopy (TEM), while the AATPS modification of NT was verified by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The results of x-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD) confirmed the presence of modified NT (mNT) in the PA dense active layer of the TFC membrane. The outgrowth of the 'leaf-like' structure, upon mNT loading, at the surface of the PA layer was observed by field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM). The TFC membrane prepared with 0.05 wt% mNT loading in the organic phase showed the water flux of 26.4 l m(-2) h(-1) when tested in the forward osmosis (FO) mode using 0.5M and 10 mM NaCl solution as the draw and feed solution, respectively. Moreover, the TFC-mNT membrane also demonstrated an intensified antifouling property against organic foulant during FO application and it was possible to retrieve the initial water flux almost completely with a simple water-rinsing process. PMID- 27405437 TI - Strategies for enhancing resveratrol production and the expression of pathway enzymes. AB - Trans-resveratrol (trans-3,5,4'-trihydroxystilbene) is one of the most promising stilbenes, a type of natural phenol that is produced naturally by some plant species in response to stress. Resveratrol exhibits multiple bioactivities and is used in the agriculture, medical, food, and cosmetic industries due to its antitumor, anti-inflammatory, cardioprotective, and antioxidant properties. Due to the increasing demand, an active area of investigation is the use of plant cell culture and metabolic engineering techniques to produce large quantities of active resveratrol. However, most recent studies have focused on the efficiency of synthesizing resveratrol in vitro, but have not investigated the contributions of the transcriptional activities of the genes encoding the related enzymes in the biosynthesis pathway. This article reviews recently developed methods for the biosynthesis of resveratrol and comprehensively reviews the current state of knowledge of the function of the key pathway enzymes in resveratrol synthesis. Approaches for enhancing resveratrol production, such as introducing non-pathway genes and co-localizing enzymes are described in detail. PMID- 27405438 TI - Biotransformation of chemical constituents of durian wine with simultaneous alcoholic fermentation by Torulaspora delbrueckii and malolactic fermentation by Oenococcus oeni. AB - This work represents the first study on the biotransformation of chemical constituents of durian wine via simultaneous alcoholic fermentation (AF) and malolactic fermentation (MLF) with non-Saccharomyces yeast and lactic acid bacteria (LAB), namely, Torulaspora delbrueckii Biodiva and Oenococcus oeni PN4. The presence of PN4 improved the utilization of sugars but did not affect ethanol production. MLF resulted in the significant degradation of malic acid with corresponding increases in pH and lactic acid. The final concentrations of acetic acid (1.29 g/L) and succinic acid (3.70 g/L) in simultaneous AF and MLF were significantly higher than that in AF (1.05 and 1.31 g/L) only. Compared with AF, simultaneous AF and MLF significantly elevated the levels of aroma compounds with higher levels of higher alcohols (isoamyl alcohol, active amyl alcohol, isobutyl alcohol, and 2-phenylethyl alcohol), acetate esters (ethyl acetate, isoamyl acetate), and ethyl esters (ethyl octanoate, ethyl dodecanoate). All the endogenous volatile sulfur compounds decreased to trace or undetectable levels at the end of fermentation. MLF accentuated the reduction of acetaldehyde and sulfides. The initially absent dipropyl disulfide was formed, then catabolized, especially in simultaneous AF and MLF. This study suggested that the simultaneous AF and MLF of non-Saccharomyces and LAB could modify the volatile compositions and potentially modulate the organoleptic properties of durian wine. PMID- 27405439 TI - Comparative genomic analysis identified a mutation related to enhanced heterologous protein production in the filamentous fungus Aspergillus oryzae. AB - Genomic mapping of mutations using next-generation sequencing technologies has facilitated the identification of genes contributing to fundamental biological processes, including human diseases. However, few studies have used this approach to identify mutations contributing to heterologous protein production in industrial strains of filamentous fungi, such as Aspergillus oryzae. In a screening of A. oryzae strains that hyper-produce human lysozyme (HLY), we previously isolated an AUT1 mutant that showed higher production of various heterologous proteins; however, the underlying factors contributing to the increased heterologous protein production remained unclear. Here, using a comparative genomic approach performed with whole-genome sequences, we attempted to identify the genes responsible for the high-level production of heterologous proteins in the AUT1 mutant. The comparative sequence analysis led to the detection of a gene (AO090120000003), designated autA, which was predicted to encode an unknown cytoplasmic protein containing an alpha/beta-hydrolase fold domain. Mutation or deletion of autA was associated with higher production levels of HLY. Specifically, the HLY yields of the autA mutant and deletion strains were twofold higher than that of the control strain during the early stages of cultivation. Taken together, these results indicate that combining classical mutagenesis approaches with comparative genomic analysis facilitates the identification of novel genes involved in heterologous protein production in filamentous fungi. PMID- 27405440 TI - Renoprotective effect of a combination of garlic and telmisartan against ischemia/reperfusion-induced kidney injury in obese rats. AB - Obesity enhances the frequency and severity of acute kidney injury (AKI). Telmisartan pre-treatment was used experimentally in the amelioration of ischemia/reperfusion (IR)-induced AKI. However, there is a lack of evidence regarding its beneficial effects on AKI in obese animals. The present study, therefore, aimed to explore the protective effects of garlic and/or telmisartan against renal damage induced by unilateral IR in obese rats. Meloxicam was used as a standard anti-inflammatory agent. Prophylactic oral administration of meloxicam (3 mg kg(-1)), garlic (500 mg kg(-1)) and/or telmisartan (5 and 10 mg kg(-1)) for 4 wk protected against renal function deterioration induced by IR in obese rats. Both doses of telmisartan significantly reduced serum total cholesterol and triacyglycerol levels as well as peri-renal adipocytes size and renal fibrosis. Renal nuclear factor-kappa B immunoreactivity, tumor necrosis factor-alpha content as well as interleukin-10, adiponectin receptor 1 and macrophages (M1, M2) polarization markers (CD11c, CD206) mRNA expressions were down-regulated in ischemic kidney tissues and white adipose tissues around them by all treatments. Moreover, garlic, telmisartan and their combinations significantly suppressed oxidative stress in renal ischemic tissues. Histological picture was also improved by these treatments. Interestingly, the combinations provided a greater protection than their monotherapy in a dose-dependent manner. We suppose that this combination may be a promising prophylactic regimen for managing AKI in case of obesity. Thus, future experimental and clinical large scale studies are necessary. PMID- 27405442 TI - Phase II Trial of Lenalidomide in HIV-Infected Patients with Previously Treated Kaposi's Sarcoma: Results of the ANRS 154 Lenakap Trial. AB - Lenalidomide, an oral immunomodulating agent, has shown promising activity in HIV infected individuals with Kaposi's sarcoma (KS). This single-arm, multicenter, open-label, Gehan's two-stage phase II trial evaluated the efficacy and safety of lenalidomide in HIV-infected patients with progressive KS despite previous chemotherapy (NCT01282047, ANRS 154 Lenakap trial). The primary endpoint was the rate of partial response (PR) or complete response (CR) at week 24, evaluated by both the study investigators and the patients using the Physical Global Assessment (PGA). AIDS Clinical Trials Group (ACTG) criteria for KS treatment evaluation were used as a secondary endpoint. The data and safety monitoring board recommended that enrollments be halted on April 24, 2013, because of lack of responses. We enrolled 12 antiretroviral-treated HIV-infected men with progressive KS despite previous chemotherapy. Their HIV plasma viral load was <50 copies/ml and their median CD4 cell count 444/mm3. One patient stopped taking lenalidomide because of hives at week 1 and a second patient died at week 7. The remaining 10 patients were assessable at week 24, when none had PGA-defined CR or PR and one had ACTG-defined PR. There were no additional PGA responses at week 48, but an additional three patients had ACTG responses, for a total of four patients with ACTG PR at week 48 (40%; 95% confidence interval: 12.2-73.8). Fourteen grade 3-4 adverse events were considered at least possibly related to lenalidomide during a total of 101 cycles. Lenalidomide was well tolerated in antiretroviral experienced patients with progressive KS previously treated with chemotherapy. The ACTG-defined response rate at week 48 was 40%, while it was 0% using PGA criteria. PMID- 27405444 TI - Liver Capsule: Multipotent stem cells and their lineage restriction to hepatocytes. PMID- 27405443 TI - Polymer physics of chromosome large-scale 3D organisation. AB - Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding. PMID- 27405445 TI - Intolerance of Uncertainty Predicts Anxiety Outcomes Following CBT in Youth with ASD. AB - Modified cognitive-behavioral therapy (MCBT) has been demonstrated to reduce anxiety in youth with autism spectrum disorder (ASD). However, non-response rates are fairly high. Few studies have investigated factors associated with response. Intolerance of uncertainty (IU) is a treatment target for anxiety and worry in neurotypical populations and has been linked to anxiety and ASD. We sought to examine whether IU affects outcomes following MCBT in 43 children, ages 8-14 years, with ASD without intellectual disability. Consistent with prior data, there was a significant reduction in parent reported anxiety following MCBT. Higher levels of pre-intervention IU predicted higher anxiety and worry pre- and post-intervention. These findings suggest that targeting IU may improve outcomes following MCBT in youth with ASD and anxiety. PMID- 27405447 TI - Sensitivity of Next-Generation Sequencing Metagenomic Analysis for Detection of RNA and DNA Viruses in Cerebrospinal Fluid: The Confounding Effect of Background Contamination. AB - Next-generation sequencing (NGS) followed by metagenomic enables the detection and identification of known as well as novel pathogens. It could be potentially useful in the diagnosis of encephalitis, caused by a variety of microorganisms. The aim of the present study was to evaluate the sensitivity of isothermal RNA amplification (Ribo-SPIA) followed by NGS metagenomic analysis in the detection of human immunodeficiency virus (HIV) and herpes simplex virus (HSV) in cerebrospinal fluid (CSF). Moreover, we analyzed the contamination background. We detected 102 HIV copies and 103 HSV copies. The analysis of control samples (two water samples and one CSF sample from an uninfected patient) revealed the presence of human DNA in the CSF sample (91 % of all reads), while the dominating sequences in water were qualified as 'other', related to plants, plant viruses, and synthetic constructs, and constituted 31 % and 60 % of all reads. Bacterial sequences represented 5.9 % and 21.4 % of all reads in water samples and 2.3 % in the control CSF sample. The bacterial sequences corresponded mainly to Psychrobacter, Acinetobacter, and Corynebacterium genera. In conclusion, Ribo SPIA amplification followed by NGS metagenomic analysis is sensitive for detection of RNA and DNA viruses. Contamination seems common and thus the results should be confirmed by other independent methods such as RT-PCR and PCR. Despite these reservations, NGS seems to be a promising method for the diagnosis of viral infections. PMID- 27405449 TI - Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro. AB - Aminoglycosides are ototoxic to the cochlear hair cells, and mitochondrial dysfunction is one of the major mechanisms behind ototoxic drug-induced hair cell death. TRMU (tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase) is a mitochondrial protein that participates in mitochondrial tRNA modifications, but the role of TRMU in aminoglycoside-induced ototoxicity remains to be elucidated. In this study, we took advantage of the HEI-OC-1 cell line to investigate the role of TRMU in aminoglycoside-induced cell death. We found that TRMU is expressed in both hair cells and HEI-OC-1 cells, and its expression is significantly decreased after 24 h neomycin treatment. We then downregulated TRMU expression with siRNA and found that cell death and apoptosis were significantly increased after neomycin injury. Furthermore, when we down-regulated TRMU expression, we observed significantly increased mitochondrial dysfunction and increased levels of reactive oxygen species (ROS) after neomycin injury, suggesting that TRMU regulates mitochondrial function and ROS levels. Lastly, the antioxidant N-acetylcysteine rescued the mitochondrial dysfunction and cell apoptosis that was induced by TRMU downregulation, suggesting that ROS accumulation contributed to the increased aminoglycosides sensitivity of HEI-OC-1 cells after TRMU downregulation. This study provides evidence that TRMU might be a new therapeutic target for the prevention of aminoglycoside-induced hair cell death. PMID- 27405450 TI - LMNA-Mediated Arrhythmogenic Right Ventricular Cardiomyopathy and Charcot-Marie Tooth Type 2B1: A Patient-Discovered Unifying Diagnosis. AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an uncommon cardiomyopathy most classically associated with mutations in genes encoding desmosomal proteins. Recent literature has identified mutations in several non desmosomal proteins including lamins that may result in the ARVC phenotype. We describe a patient who discovered her own pathogenic LMNA mutation that offered a unifying diagnosis explaining her ARVC and Charcot-Marie-Tooth phenotypes as well as musculoskeletal abnormalities. Suspicion for LMNA-mediated cardiomyopathy should arise in patients with extracardiac manifestations of laminopathies and testing for specific gene mutations may be helpful in establishing an unifying diagnosis. PMID- 27405451 TI - Bipolar Radiofrequency Ablation of Typical Atrial Flutter. PMID- 27405452 TI - The effect of heat treatment simulating porcelain firing processes on titanium corrosion resistance. AB - PURPOSE: Corrosion resistance of titanium used in metal-ceramic restorations in manufacturing is based on the presence of oxide layer on the metal surface. The procedures used during combining metallic material with porcelain may affect the changes in oxide layers structure, and thus anticorrosive properties of metallic material. The aim of the study was an evaluation of potential changes in the structure and selected corrosion properties of titanium after sandblasting and thermal treatment applicable to the processes of ceramics fusion. METHODS: Milled titanium elements were subjected to a few variants of the processes typical of ceramics fusion and studied in terms of resistance to electrochemical corrosion. The study included the OCP changes over time, measurements of Icorr, Ecorr and Rp as well as potentiodynamic examinations. Surface microstructure and chemical composition were analyzed using SEM and EDS methods. RESULTS: The results obtained allow us to conclude that the processes corresponding to ceramic oxidation and fusion on titanium in the variants used in the study do not cause deterioration of its anticorrosive properties, and partially enhance the resistance. This depends on the quality of oxide layers structure. CONCLUSIONS: Titanium elements treated by porcelain firing processes do not lose their corrosion resistance. PMID- 27405453 TI - High type II error and interpretation inconsistencies when attempting to refute transgenerational epigenetic inheritance. AB - A recently published article in Genome Biology attempts to refute important aspects of the phenomenon of transgenerational epigenetic inheritance (TEI). An alternative explanation of the data is offered here, showing that TEI is indeed not contradicted.Please see related Correspondence article: www.dx.doi.org/10.1186/s13059-016-0981-5 and related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0619-z. PMID- 27405454 TI - Beliefs underlying Women's intentions to consume alcohol. AB - BACKGROUND: Changing trends demonstrate that women, in a number of economically developed countries, are drinking at higher levels than ever before. Exploring key targets for intervention, this study examined the extent to which underlying beliefs in relation to alcohol consumption predicted intentions to drink in three different ways (i.e. low risk drinking, frequent drinking and binge drinking). METHODS: Utilizing a prospective design survey, women (N = 1069), aged 18-87 years, completed a questionnaire measuring their beliefs and intentions regarding alcohol consumption. Then, two weeks later, 845 of the original sample, completed a follow-up questionnaire reporting their engagement in the drinking behaviors. A mixed design ANOVA was conducted to examine potential differences between women of different age groups (18-24, 25-34, 35-44, 45-54, 55 years and above) and their intentions to engage in the three different drinking behaviors. Based upon The Theory of Planned Behavior, critical beliefs analyses were carried out to identify key determinants underlying intentions to engage in the three different drinking behaviors. RESULTS: Significant effects of age were found in relation to frequent and binge drinking. The critical beliefs analyses revealed that a number of behavioral, control and normative beliefs were significant predictors of intentions. These beliefs varied according to age group and drinking behavior. CONCLUSIONS: Previously unidentified key factors that influence women's decisions to drink in certain ways have been established. Overall, future interventions and public policy may be better tailored so as to address specific age groups and drinking behaviors. PMID- 27405456 TI - Are General Physicians Prepared for Struggling Skin Cancer?-Cross-Sectional Study. AB - The aim of this study is to evaluate the role of general practitioners (GP) in selecting higher risk population for skin cancer screening. GP's training was organized to examine a specific high risk population consisting mainly of fisherman and farmers in a city of North of Portugal. Health care professionals of local health units training was performed by two dermatologists 2 months before the screening. During 8 weeks GPs selected patients with skin cancer suspicious lesions and/or risk factors consecutively from their regular consultation. These selected patients were referred to a dermatologist evaluation. Six dermatologists using manual dermoscopy examined the previously selected patients. One hundred eight patients have been screened, 35 % of which were males and 65 % females, with a mean age of 54 years. Full skin evaluation by dermatologists revealed 31 % of actinic keratosis, 5 % of leucoplasia, 7 % of basal cell carcinoma, 8 % of squamous cell carcinoma, and 1 % of melanoma. Cohen's kappa coefficient between dermatologist and GPs was 0.18. Selective screening with collaboration of GPs allowed the detection of more cases of skin cancer than the nonselective screenings in the literature. Although the diagnostic agreement between GPs and dermatologists was not good, our results indicate that active collaboration of dermatologists with primary health care units for selective skin cancer screening, including post graduated courses on their own health units, can be a way of optimizing early detection of cutaneous pre malignant and malignant lesions. PMID- 27405457 TI - [Achilles tendon rupture : Current diagnostic and therapeutic standards]. AB - A superior life expectancy and an increased activity in the population result in an increase in degenerative diseases, such as Achilles tendon ruptures. The medical history and physical examinations are the methods of choice to diagnose Achilles tendon ruptures. Ultrasound and radiography represent reasonable extended diagnostic procedures. In order to decide on the medical indications for the therapy concept, the advantages and disadvantages of conservative and surgical treatment options have to be weighed up on an indivdual basis. There are explicit contraindications for both treatment options. For the surgical treatment concept open suture techniques, minimally invasive methods and reconstructive procedures are available. The postoperative management of the patient is as important as the choice of surgical technique. With the correct medical indications and supervision of the patient it is possible to achieve extremely satisfying results for the patient with both conservative and surgical treatment options. PMID- 27405458 TI - [Surgical treatment of talocalcaneal coalition : Experience with 80 cases of pediatric or adolescent patients]. AB - INTRODUCTION: There is still a controversial discussion on the treatment of talocalcaneal coalition with and without planovalgus deformity. From 2002-2014 80 cases of talocalcaneal coalition in children and adolescents under 18 years of age were surgically treated by J. Hamel. The objective of this study is a retrospective analysis, especially of unfavourable results. METHODS: Patients with minimum follow up of 12 months were included (35.7 months on average). In 31 cases treatment consisted of resection and fat-grafting (group 1), in 26 additional cases tarsal osteotomy was added because of planovalgus-deformity (group 2), and in 23 cases primary fusion of the talocalcaneal joint was performed (group 3). RESULTS: In group 1 one patient was lost to follow-up early with a severe peroneal spasticity and unknown further course. Two further patients still had remarkable pain after 15 months, and another patient had to undergo secondary fusion because of persistent pain. In group 2 secondary fusion was undertaken in two cases and offered in four other cases. In group 3 two patients still suffered from moderate tarsal pain, although complete fusion occurred; one of these patients underwent bilateral treatment. All other patients were pain free or nearly pain free on the last follow-up visit, with marked improvement in comparison to the preoperative situation. DISCUSSION: Surgical treatment of talocalcaneal coalition is successful in most cases in the short to medium follow-up, but unfavourable results are not uncommon and may require secondary fusion. Differential indication between resection, additional deformity correction, or primary fusion seems to be most important. PMID- 27405459 TI - Association between regular physical exercise and depressive symptoms mediated through social support and resilience in Japanese company workers: a cross sectional study. AB - BACKGROUND: Regular physical exercise has been reported to reduce depressive symptoms. Several lines of evidence suggest that physical exercise may prevent depression by promoting social support or resilience, which is the ability to adapt to challenging life conditions. The aim of this study was to compare depressive symptoms, social support, and resilience between Japanese company workers who engaged in regular physical exercise and workers who did not exercise regularly. We also investigated whether regular physical exercise has an indirect association with depressive symptoms through social support and resilience. METHODS: Participants were 715 Japanese employees at six worksites. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression (CES D) scale, social support with the short version of the Social Support Questionnaire (SSQ), and resilience with the 14-item Resilience Scale (RS-14). A self-report questionnaire, which was extracted from the Japanese version of the Health-Promoting Lifestyle Profile, was used to assess whether participants engage in regular physical exercise, defined as more than 20 min, three or more times per week. The group differences in CES-D, SSQ, and RS-14 scores were investigated by using analysis of covariance (ANCOVA). Mediation analysis was conducted by using Preacher and Hayes' bootstrap script to assess whether regular physical exercise is associated with depressive symptoms indirectly through resilience and social support. RESULTS: The SSQ Number score (F = 4.82, p = 0.03), SSQ Satisfaction score (F = 6.68, p = 0.01), and RS-14 score (F = 6.01, p = 0.01) were significantly higher in the group with regular physical exercise (n = 83) than in the group without regular physical exercise (n = 632) after adjusting for age, education, marital status, and job status. The difference in CES-D score was not significant (F = 2.90, p = 0.09). Bootstrapping revealed significant negative indirect associations between physical exercise and CES-D score through the SSQ Number score (bias-corrected and accelerated confidence interval (BCACI) = -0.61 to -0.035; 95 % confidence interval (CI)), SSQ Satisfaction score (BCACI = -0.92 to -0.18; 95 % CI), and RS-14 score (BCACI = 1.89 to -0.094; 95 % CI). CONCLUSION: Although we did not find a significant direct association between exercise and depressive symptoms, exercise may be indirectly associated with depressive symptoms through social support and resilience. Further investigation is warranted. PMID- 27405460 TI - The FANCD2-FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2. AB - The Fanconi anaemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2-FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here, we report the first structural insight into the human FANCD2-FANCI complex by obtaining the cryo-EM structure. The complex contains an inner cavity, large enough to accommodate a double-stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain are observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2-FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain. PMID- 27405461 TI - Ischiofemoral impingement syndrome: a case report redefining this condition. PMID- 27405462 TI - Expression of PR-protein genes and induction of defense-related enzymes by Bacillus subtilis CBR05 in tomato (Solanum lycopersicum) plants challenged with Erwinia carotovora subsp. carotovora. AB - The present study was aimed to evaluate the effectiveness of a biocontrol agent Bacillus subtilis CBR05 for control of soft rot disease (Erwinia carotovora subsp. carotovora) in tomato, and the possible mechanisms of its resistance induction have been investigated under pot conditions. Results showed that plants inoculated with B. subtilis CBR05 had lower disease incidence (36%). A significant increase in superoxide dismutase, catalase, peroxidase, and polyphenol oxidase activities was observed in plants inoculated with B. subtilis between 48 and 72 hpi. Also, the transcript profiles of Glu and Phenyl ammonia lyase (PAL) showed a significant up-regulation following inoculation. The most significant up-regulation was observed in transcript profile of PAL that showed 0.49 Fold Expression, at 72 hpi as compared to its expression at 12 hpi. These results suggest that systemic induction of defense-related genes expression and antioxidant enzyme activity by B. subtilis could play a pivotal role in disease resistance against soft rot disease. PMID- 27405464 TI - Design and development of a microarray processing station (MPS) for automated miniaturized immunoassays. AB - Here we describe the design and evaluation of a fluidic device for the automatic processing of microarrays, called microarray processing station or MPS. The microarray processing station once installed on a commercial microarrayer allows automating the washing, and drying steps, which are often performed manually. The substrate where the assay occurs remains on place during the microarray printing, incubation and processing steps, therefore the addressing of nL volumes of the distinct immunoassay reagents such as capture and detection antibodies and samples can be performed on the same coordinate of the substrate with a perfect alignment without requiring any additional mechanical or optical re-alignment methods. This allows the performance of independent immunoassays in a single microarray spot. PMID- 27405463 TI - A CONSTANS-like transcriptional activator, OsCOL13, functions as a negative regulator of flowering downstream of OsphyB and upstream of Ehd1 in rice. AB - Flowering time determines the adaptability of crop plants to different local environments, thus being one of the most important agronomic traits targeted in breeding programs. Photoperiod is one of the key factors that control flowering in plant. A number of genes that participate in the photoperiod pathway have been characterized in long-day plants such as Arabidopsis, as well as in short-day plants such as Oryza sativa. Of those, CONSTANS (CO) as a floral integrator promotes flowering in Arabidopsis under long day conditions. In rice, Heading date1 (Hd1), a homologue of CO, functions in an opposite way, which inhibits flowering under long day conditions and induces flowering under short day conditions. Here, we show that another CONSTANS-like (COL) gene, OsCOL13, negatively regulates flowering in rice under both long and short day conditions. Overexpression of OsCOL13 delays flowering regardless of day length. We also demonstrated that OsCOL13 has a constitutive and rhythmic expression pattern, and that OsCOL13 is localized to the nucleus. OsCOL13 displays transcriptional activation activity in the yeast assays and likely forms homodimers in vivo. OsCOL13 suppresses the florigen genes Hd3a and RFT1 by repressing Ehd1, but has no relationship with other known Ehd1 regulators as determined by using mutants or near isogenic lines. In addition, the transcriptional level of OsCOL13 significantly decreased in the osphyb mutant, but remained unchanged in the osphya and osphyc mutants. Thus, we conclude that OsCOL13 functions as a negative regulator downstream of OsphyB and upstream of Ehd1 in the photoperiodic flowering in rice. PMID- 27405465 TI - Identifying the conditions needed for integrated knowledge translation (IKT) in health care organizations: qualitative interviews with researchers and research users. AB - BACKGROUND: Collaboration among researchers and research users, or integrated knowledge translation (IKT), enhances the relevance and uptake of evidence into policy and practice. However, it is not widely practiced and, even when well resourced, desired impacts may not be achieved. Given that large-scale investment is not the norm, further research is needed to identify how IKT can be optimized. METHODS: Interviews were conducted with researchers and research users (clinicians, managers) in a health care delivery (HCDO) and health care monitoring (HCMO) organization that differed in size and infrastructure, and were IKT-naive. Basic qualitative description was used. Participants were asked about IKT activities and challenges, and recommendations for optimizing IKT. Data were analysed inductively using constant comparative technique. RESULTS: Forty-three interviews were conducted (28 HCDO, 15 HCMO) with 13 researchers, 8 clinicians, and 22 managers. Little to no IKT took place. Participants articulated similar challenges and recommendations revealing that a considerable number of changes were needed at the organizational, professional and individual levels. Given the IKT-absent state of participating organizations, this research identified a core set of conditions which must be addressed to prepare an environment conducive to IKT. These conditions were compiled into a framework by which organizations can plan for, or evaluate their capacity for IKT. CONCLUSIONS: The IKT capacity framework is relevant for organizations in which there is no current IKT activity. Use of the IKT framework may result in more organizations that are ready to initiate and establish IKT, perhaps ultimately leading to more, and higher-quality collaboration for health system innovation. Further research is needed to confirm these findings in other organizations not yet resourced for, or undertaking IKT, and to explore the resource implications and mechanisms for establishing the conditions identified here as essential to preparing for IKT. PMID- 27405466 TI - Optical Properties of Plasmonic Mirror-Image Nanoepsilon. AB - We propose a novel mirror-image nanoepsilon (MINE) structure to achieve highly localized and enhanced near field at its gap and systematically investigate its plasmonic behaviors. The MINE can be regarded as a combination of two fundamental plasmonic nanostructures: a nanorod dimer and nanoring. By adapting a nanoring surrounding a nanorod dimer structure, the nanorod is regarded as a bridge pulling the charges from the nanoring to the nanorod, which induces stronger plasmon coupling in the gap to boost local near-field enhancement. Two resonance peaks are identified as the symmetric and anti-symmetric modes according to the symmetries of the charge distributions on the ring and rod dimer in the MINE. The symmetric mode in the MINE structure is preferred because its charge distribution leads to stronger near-field enhancement with a concentrated distribution around the gap. In addition, we investigate the influence of geometry on the optical properties of MINE structures by performing experiments and simulations. These results indicate that the MINE possesses highly tunable optical properties and that significant near-field enhancement at the gap region and rod tips can be realized by the gap and lightning-rod effects. The results improve understanding of such complex systems, and it is expected to guide and facilitate the design of optimum MINE structures for various plasmonic applications. PMID- 27405467 TI - Sulfate Exchange of the Nitrate-Type Layered Hydroxide Nanosheets of Ln2(OH)5NO3.nH2O for Better Dispersed and Multi-color Luminescent Ln2O3 Nanophosphors (Ln = Y0.98RE0.02, RE = Pr, Sm, Eu, Tb, Dy, Ho, Er, and Tm). AB - Through restricting thickness growth by performing coprecipitation at the freezing temperature of ~4 degrees C, solid-solution nanosheets (up to 5-nm thick) of the Ln2(OH)5NO3.nH2O layered hydroxide (Ln = Y0.98RE0.02; RE = Pr, Sm, Eu, Tb, Dy, Ho, Er, and Tm, respectively) were directly synthesized without performing conventional exfoliation. In situ exchange of the interlayer NO3 (-) with SO4 (2-) produced a sulfate derivative [Ln2(OH)5(SO4)0.5.nH2O] of the same layered structure and two-dimensional crystallite morphology but substantially contracted d 002 basal spacing (from ~0.886 to 0.841 nm). The sulfate derivative was systematically compared against its nitrate parent in terms of crystal structure and phase/morphology evolution upon heating. It is shown that the interlayer SO4 (2-), owing to its bonding with the hydroxide main layer, significantly raises the decomposition temperature from ~600 to 1000 degrees C to yield remarkably better dispersed oxide nanopowders via a monoclinic Ln2O2SO4 intermediate. The resultant (Y0.98RE0.02)2O3 nanophosphors were studied for their photoluminescence to show that the emission color, depending on RE(3+), spans a wide range in the Commission Internationale de l'Eclairage (CIE) chromaticity diagram, from blue to deep red via green, yellow, orange, and orange red. PMID- 27405469 TI - IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway. AB - Interleukin-33 (IL-33) is a recently identified member of the IL-1 family that exerts biologic functions by binding to a heterodimer composed of IL-1 receptor related protein ST2L and IL-1RAcP. However, the role of IL-33 and whether IL-33 accounts for inflammation, apoptotic, and autophagic neuropathology after intracerebral hemorrhage (ICH) are not clear. Here, we established a mouse ICH model in this study, to determine the role of IL-33 and explore the underlying mechanism. Male mice were subjected to an infusion of type IV collagenase/saline into the left striatum to induce ICH/sham model. IL-33, soluble ST2 (sST2), or saline were also administered by a single intracerebroventricular (i.c.v.) injection, respectively. The results showed that the expression level of IL-33 markedly decreased within 6 h and reached the valleys at 6 and 72 h after ICH vs. sham group. In parallel, ST2L (a transmembrane form receptor of IL-33) significantly increased within 6 h and reached the peaks at 6 h and 24 h after ICH vs. sham group. In addition, administration of IL-33 alleviated cerebral water contents, reduced the number of PI- and TUNEL-positive cells, and improved neurological function after ICH. Moreover, IL-33 treatment apparently suppressed the expression of pro-inflammation cytokines IL-1beta and TNF-alpha, evidently increased Bcl-2 but decreased cleaved-caspase-3, and obviously decreased the levels of autophagy-associated proteins LC3-II and Beclin-1 but maintained P62 at high level after ICH. On the contrary, treatment with sST2, a decoy receptor of IL-33, exacerbated ICH-induced brain damage and neurological dysfunction by promoting apoptosis, and enhancing autophagic activity. In conclusion, IL-33 provides neuroprotection through suppressing inflammation, apoptotic, and autophagic activation in collagenase-induced ICH model. PMID- 27405468 TI - Genome-wide Analysis of RARbeta Transcriptional Targets in Mouse Striatum Links Retinoic Acid Signaling with Huntington's Disease and Other Neurodegenerative Disorders. AB - Retinoic acid (RA) signaling through retinoic acid receptors (RARs), known for its multiple developmental functions, emerged more recently as an important regulator of adult brain physiology. How RAR-mediated regulation is achieved is poorly known, partly due to the paucity of information on critical target genes in the brain. Also, it is not clear how reduced RA signaling may contribute to pathophysiology of diverse neuropsychiatric disorders. We report the first genome wide analysis of RAR transcriptional targets in the brain. Using chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis of RARbeta-null mutant mice, we identified genomic targets of RARbeta in the striatum. Characterization of RARbeta transcriptional targets in the mouse striatum points to mechanisms through which RAR may control brain functions and display neuroprotective activity. Namely, our data indicate with statistical significance (FDR 0.1) a strong contribution of RARbeta in controlling neurotransmission, energy metabolism, and transcription, with a particular involvement of G-protein coupled receptor (p = 5.0e-5), cAMP (p = 4.5e-4), and calcium signaling (p = 3.4e-3). Many identified RARbeta target genes related to these pathways have been implicated in Alzheimer's, Parkinson's, and Huntington's disease (HD), raising the possibility that compromised RA signaling in the striatum may be a mechanistic link explaining the similar affective and cognitive symptoms in these diseases. The RARbeta transcriptional targets were particularly enriched for transcripts affected in HD. Using the R6/2 transgenic mouse model of HD, we show that partial sequestration of RARbeta in huntingtin protein aggregates may account for reduced RA signaling reported in HD. PMID- 27405470 TI - Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice. AB - The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ?. PMID- 27405472 TI - A small angle X-ray scattering study of the structure and development of looseness in bovine hides and leather. AB - BACKGROUND: Some bovine hides produce poor quality leather, termed loose leather. The structural characteristics of hides and the intermediate processed stages that lead to loose leather are not well understood. In the present study, synchrotron-based small angle X-ray scattering (SAXS) is used to investigate collagen fibril orientation at the different stages of processing (i.e. from hide through to leather) that result in both tight and loose leathers. RESULTS: Tight leather of a relatively isotropic texture has a lower orientation index (OI) than loose leather of a more pronounced stratified texture; conversely, tight pickled hide and wet blue have a higher OI than loose pickled hide and wet blue. There is a greater increase in OI on processing from pickled hide to dry crust (leather) for loose material. This is largely the result of a greater increase in hide thickness prior to pickling for loose hide than tight hide, followed by a greater decrease at the dry crust stage. The collagen fibrils in loose leather and wet blue more readily orient under stress than do those in tight leather. Loose leather has a more pronounced layered structure than tight leather, although this difference is not apparent from SAXS measurements of hide prior to the dry crust stage; it develops during processing. CONCLUSION: The greater swelling of the loose hide during processing disrupts the structure and leads to a more layered collagen arrangement on shrinking at the final dry crust stage. (c) 2016 Society of Chemical Industry. PMID- 27405471 TI - Breast cancer policy in Latin America: account of achievements and challenges in five countries. AB - BACKGROUND: The recent increase of breast cancer mortality has put on alert to most countries in the region. However it has taken some time before breast cancer could be considered as a relevant problem. Only in recent years breast cancer has been considered a priority in some Latin American countries and resources have been mobilized to confront the problem at the institutional level. The article analyzes the efforts made in five Latin American countries (Argentina, Brazil, Colombia, Mexico and Venezuela) in the last 15 years to design and implement policies to address the growing incidence of breast cancer. METHODS: Data was collected between July and December 2010 from both primary and secondary sources. Semi-structured interviews were conducted with key informants from governmental and non-governmental organizations. Secondary data was obtained from publications in journals, government reports and official statistics in each country. Analysis combines information from both types of sources. RESULTS: Countries have followed different paths and are in different stages of policy implementation. In all cases early detection is a key strategy. Through the design of programs and guidelines, the allocation of financial resources to treat patients, as well as a formally structured information system, Brazil and Mexico have been able to set up comprehensive national policies. Argentina, Colombia and Venezuela have made important advancements but not yet capable of coordinating comprehensive national policies. CONCLUSION: Breast cancer is being considered a priority in all five countries but there are different stages in the rolling out of comprehensive national policies due to differences in their capacity to allocate resources, implement operational strategies and encourage the participation of relevant stakeholders. PMID- 27405473 TI - Distinct expression and function of carotenoid metabolic genes and homoeologs in developing wheat grains. AB - BACKGROUND: beta-carotene, the most active provitamin A molecule produced by plants, plays important roles in human nutrition and health. beta-carotene does not usually accumulate in the endosperm (i.e. flour) of mature wheat grains, which is a major food source of calories for humans. Therefore, enriching beta carotene accumulation in wheat grain endosperm will enable a sustainable dietary supplementation of provitamin A. Several metabolic genes affecting beta-carotene accumulation have already been isolated from wheat, including phytoene synthase 1 (PSY1), lycopene epsilon-cyclase (LCYe) and carotenoid beta-ring hydroxylase1/2 (HYD1/2). RESULTS: In this work, we cloned and biochemically characterized two carotenoid cleavage dioxygenases (CCDs), CCD1 and CCD4, from wheat. While CCD1 homoeologs cleaved beta-apo-8'-carotenal, beta-carotene, lutein and zeaxanthin into apocarotenoid products, CCD4 homoeologs were inactive towards these substrates in in vitro assays. When analyzed by real-time qPCR, PSY1, LCYe, HYD1/2 and CCD1/4 homoeologs showed distinct expression patterns in vegetative tissues and sections of developing tetraploid and hexaploid wheat grains, suggesting that carotenoid metabolic genes and homoeologs are differentially regulated at the transcriptional level in wheat. CONCLUSIONS: The CCD1/4 enzyme activity and the spatial-temporal gene expression data provide critical insights into the specific carotenoid metabolic gene homoeologs that control beta-carotene accumulation in wheat grain endosperm, thus establishing the knowledge base for generation of wheat varieties with enhanced beta-carotene in the endosperm through breeding and genome editing approaches. PMID- 27405476 TI - RETRACTION Novel perspectives on hypothalamic-pituitary dysfunction as a risk factor for non-alcoholic fatty liver disease. AB - Minerva Endocrinologica is retracting the paper by Anika HOFFMANN, Hermann L. MULLER, "Novel perspectives on hypothalamic-pituitary dysfunction as a risk factor for nonalcoholic fatty liver disease" (Minerva Endocrinologica 2017 June;42(2):132-44). PMID- 27405474 TI - Insulin-like growth factor-1 signaling in renal cell carcinoma. AB - Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells. PMID- 27405478 TI - The effects of bariatric surgeries on nonalcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with obesity. Bariatric surgery has been shown to be the most effective method for weight reduction. However, no conclusive data exists on the effects of weight reduction surgery on NAFLD. This study aimed to characterize liver histology, metabolic status, and liver function changes in patients who underwent bariatric surgery, before and after the weight-reduction procedure. This is a phase 1 report of a prospective cohort study of patients who underwent bariatric surgery. Biopsies were obtained at baseline (intraoperatively) and 3 months postoperatively. Clinical characteristics, biochemical profile, and histopathological data [steatosis, NAFLD activity score (NAS), hepatocyte ballooning, lobular inflammation, and degree of fibrosis] were obtained at each time point. Twenty-seven patients were included (9 men and 18 women), and the median age was 35 +/- 8 years old. At baseline, 3 patients had dyslipidemia, 4 had diabetes, and 5 patients had hypertension, which did not change at follow-up. The average body mass index decreased from 44.6 +/- 7.8 to 34.2 +/- 6.3 kg/m2 at follow-up (P < 0.001). On histopathology, 12 of the 18 patients with preoperative steatosis (median score 2) had reduced steatosis scores postoperatively (P = 0.025); fibrosis (median score 1) was also reduced in 17 patients (P = 0.012), and NAS was decreased from 4 (3-5) to 2 (1-3) (P = 0.004). The changes in lobular inflammation and hepatocyte ballooning were not statistically significant on follow-up. The phase 1 results of this study described the histopathological changes following weight reduction surgery and suggested that hepatic steatosis, fibrosis, and NAFLD activity score were reduced 3 months after surgery. This clinical trial is financially supported by the National Plan for Science, Technology and Innovation Program grant number (11 MED1910-02). PMID- 27405479 TI - Erratum to: A feasibility study of the use of computed virtual chromoendoscopy for laparoscopic evaluation of peritoneal metastases. PMID- 27405477 TI - SAGES guidelines for laparoscopic ventral hernia repair. PMID- 27405480 TI - Clinical features of negative pathologic results after gastric endoscopic submucosal dissection. AB - BACKGROUND: Endoscopic submucosal dissection (ESD) is widely used for the treatment of gastric superficial neoplasms. Negative pathologic results after ESD can confuse the endoscopists and patients. The aim of this study was to evaluate the reasons for and the factors associated with negative pathologic results after ESD. PATIENTS AND METHODS: From December 2008 to July 2015, a total of 1379 lesions diagnosed as definite dysplasia or adenocarcinoma by endoscopic forceps biopsy (EFB) were removed with an ESD procedure. The initial endoscopic and pathologic findings were analyzed. RESULTS: The incidence of negative pathology after ESD was 2.0 % (28/1379). Compared with positive pathologic lesions, negative pathologic lesions were smaller and had less surface area (P < 0.001). The reasons for negative pathologic lesions after ESD were complete removal by EFB (n = 20), over-estimations of the EFB specimen (n = 5), and different ESD site (n = 3). CONCLUSION: Small tumor size and surface area are associated with negative pathologic results after ESD. When negative pathologic results are reported after ESD, we should review the previous endoscopic biopsy tissue specimen and compare the previous EFB site to the ESD site. Thereafter, regular endoscopic examination of the lesion is needed. PMID- 27405481 TI - A combined thoracoscopic and laparoscopic approach for high epiphrenic diverticula and the importance of complete myotomy. AB - BACKGROUND: The traditional approach to epiphrenic diverticula is thoracotomy and diverticulectomy, together with myotomy +/- partial fundoplication to address underlying dysmotility. A laparoscopic approach has been advocated but access to more proximal diverticula is problematic. We propose the selective addition of a thoracoscopic approach to overcome these challenges and reviewed our results. METHODS: A retrospective review from 2004 to 2015 identified 17 patients with an epiphrenic diverticulum who underwent surgery. Patients were grouped according to height of the diverticular neck (HDN) above the GEJ: group A < 5 cm, group B > 5 cm. Preoperative evaluation and type of surgery performed were recorded. Postoperative complications, mortality, and clinical outcomes using quality of life metrics and objective testing were assessed. RESULTS: The mean size of the diverticulum was 3.3 cm (2-6 cm) with a mean height above the GEJ of 5.5 cm (0-12 cm). A motility disorder was identified in 15/17. Group A, 9 patients, underwent laparoscopic diverticulectomy, myotomy, and partial fundoplication. For group B, 8 patients, the intended procedure was thoracoscopic diverticulectomy followed by laparoscopic myotomy and partial fundoplication, but this was only completed in 5. In 3 the myotomy was aborted or incomplete with subsequent staple line leaks resulting in 1 death. At a mean follow-up of 21 months, improvement of median QOLRAD scores from 3.42 to 6.2 (p = 0.18); GERD-HRQL from 23 to 1 (p = 0.05), swallowing score from 17.5 to 30 (p = 0.22), and Eckardt scores from 5 to 0 (p < 0.05) were observed. CONCLUSIONS: A minimally invasive strategy for epiphrenic diverticula based HDN above the GEJ and selective thoracoscopy for higher diverticula is feasible and appropriate, and resulted in improved quality of life. Incomplete myotomy was associated with a substantially higher complication rate. Laparoscopic myotomy should precede diverticulectomy for all cases, especially for high diverticula. PMID- 27405482 TI - Laparoscopic duodenojejunostomy for superior mesenteric artery syndrome: intermediate follow-up results and a review of the literature. AB - BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare condition caused by partial obstruction of the third portion of the duodenum by the SMA anteriorly and aorta posteriorly. Laparoscopic duodenojejunostomy has been described as a safe and feasible surgical intervention with favorable short-term outcomes. However, descriptions of intermediate outcomes are lacking in the literature. METHODS: A retrospective chart review was performed on patients who underwent minimally invasive duodenojejunostomy from March 2005 to August 2015 at our healthcare system with greater than 6-month follow-up. RESULTS: Eighteen patients with mean age of 31.2 were identified. There were 4 men and 14 women. Patients' diagnosis was made by clinical presentation with radiographic confirmation. Mean weight loss preoperatively was 13.9 kg, representing 24.1 % total body weight loss. There were no intraoperative complications. Postoperatively, 2 patients developed prolonged ileus. One underwent exploratory laparotomy and washout for presumed leak, but none was identified. Three patients were readmitted within 30 days; 2 for intolerance to enteral intake with dehydration, and 1 for closed-loop obstruction requiring laparoscopic lysis of adhesions. The average and median length of follow-up were 27.7 and 26.0 months, respectively. Patients gained an average of 2.2 kg with an increase in body mass index of from 19.6 to 20.4 m/kg2. Although 14 of 18 patients reported initial symptom improvement, at latest follow up, only 6 patients reported symptomatic improvement or resolution. Three were diagnosed with global dysmotility, and 1 underwent intestinal transplant. Two were diagnosed with gastroparesis, and 1 underwent a laparoscopic gastric electric stimulator placement and pyloroplasty. There were no mortalities. CONCLUSION: Duodenojejunostomy is the most common surgical intervention in management of SMAS. Our intermediate follow-up reveals infrequent improvement and rare resolution of preoperative symptomatology. Patients had a modest average weight gain postoperatively. This may suggest that different preoperative workup and treatment is indicated. PMID- 27405483 TI - Video-assisted thoracoscopic surgery is a safe option for benign lung diseases requiring lobectomy. AB - BACKGROUND: Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated. METHODS: We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the chi 2 test and Student's t test; any p value <=0.05 was considered as significant. RESULTS: Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (p < 0.001), history of cancer (p < 0.001), history of stroke (p = 0.05), and the presence of pleural adhesions (p = 0.03). There was no difference for duration of air leaks, chest tube drainage and hospital stay, conversion rate, and perioperative complication rate. CONCLUSIONS: We conclude that pathology did not impact on outcomes after VATS lobectomy. This study suggests that VATS is as a safe option in selected patients with benign disease requiring lobectomy, despite a more complex technical context. PMID- 27405484 TI - Lack of association of poultry and eggs intake with risk of non-Hodgkin lymphoma: a meta-analysis of observational studies. AB - We carried out a meta-analysis to explore the association between poultry and eggs consumption and non-Hodgkin lymphoma (NHL) risk according to the published observational studies. A search of databases was performed in MEDLINE and EMBASE from their inception to March 2015. We derived meta-analytic estimates using random-effects models, and assessed between-study heterogeneity using the Cochran's Q and I2 statistics. We identified a total of nine case-control and three prospective cohort studies, including 11,271 subjects with NHL. The summary relative risks for high vs. low analyses were 1.04 (95% confidence intervals [CIs]: 0.86-1.27; pheterogeneity <.001, I2 = 84.0%) for poultry consumption and 1.15 (95% CIs: 0.87-1.51; pheterogeneity <.001, I2 = 85.3%) for egg consumption. Meta-regression analysis showed that study locations, study quality, type of Food Frequency Questionnaire and confounders adjusted for total energy intake contributed to the high heterogeneity among the studies on poultry consumption, whereas no significant factors were responsible for the high heterogeneity among the studies on eggs consumption. Limited data suggested a null association between consumption of poultry and eggs and NHL subtypes. Findings from our meta analysis indicate that consumption of poultry and eggs may be not related to NHL risk. PMID- 27405486 TI - Association between temporomandibular disorders and music performance anxiety in violinists. AB - BACKGROUND: Professional violin playing has been associated with a predisposition to develop temporomandibular disorder (TMD). There are a number of risk factors, including physical trauma from the playing posture and the presence of parafunctional habits. Music performance anxiety (MPA) may also be a factor, as it has been associated with playing-related musculoskeletal disorders (PRMD). AIMS: To evaluate a possible association between the presence of TMD and the level of MPA in violin players. METHODS: An observational study using a written questionnaire that retrieved data related to TMD symptoms (Fonseca Anamnestic Questionnaire), MPA level (Kenny Music Performance Anxiety Inventory, K-MPAI), instrument practice time, chinrest type, sex and age. Descriptive, bivariate and logistic regression analyses were conducted. RESULTS: Ninety-three professional or semi-professional violinists performing in and around Lisbon, Portugal, completed the questionnaire (73% response rate). TMD was present in 50 violinists (58%). There was a statistically significant association between the presence of TMD and high MPA levels (P < 0.001) and the most anxious violinists were six times (95% confidence interval 2.51-15.33; P < 0.001) more likely to report TMD symptoms when compared with the least anxious players. CONCLUSIONS: Violin players had a high prevalence of reported TMD symptoms, which was significantly associated with high MPA levels. It may therefore be necessary to address psychological and physical factors simultaneously in musicians who do not improve with physical therapy alone. PMID- 27405488 TI - National body is considering a single register for all health and care professionals. PMID- 27405485 TI - Control of autoimmune inflammation by celastrol, a natural triterpenoid. AB - Celastrol is a bioactive compound derived from traditional Chinese medicinal herbs of the Celastraceae family. Celastrol is known to possess anti-inflammatory and anti-oxidant activities. Our studies have highlighted the immunomodulatory attributes of celastrol in adjuvant-induced arthritis (AA), an experimental model of human rheumatoid arthritis (RA). RA is an autoimmune disease characterized by chronic inflammation of the synovial lining of the joints, leading eventually to tissue damage and deformities. Identification of the molecular targets of celastrol such as the NF-kappaB pathway, MAPK pathway, JAK/STAT pathway and RANKL/OPG pathway has unraveled its strategic checkpoints in controlling arthritic inflammation and tissue damage in AA. The pathological events that are targeted and rectified by celastrol include increased production of pro inflammatory cytokines; an imbalance between pathogenic T helper 17 and regulatory T cells; enhanced production of chemokines coupled with increased migration of immune cells into the joints; and increased release of mediators of osteoclastic bone damage. Accordingly, celastrol is a promising candidate for further testing in the clinic for RA therapy. Furthermore, the results of other preclinical studies suggest that celastrol might also be beneficial for the treatment of a few other autoimmune diseases besides arthritis. PMID- 27405487 TI - Post-exposure treatment with whole inactivated H5N1 avian influenza virus protects against lethal homologous virus infection in mice. AB - Concerns with H5N1 influenza viruses include their prevalence in wild and domestic poultry, high mortality rate (~60%) in humans with some strains, lack of pre-existing immunity in humans, and the possibility that these viruses acquire mutations that enable efficient transmission between humans. H5 subtype viruses of Eurasian origin have recently appeared in wild and domestic bird populations in North America, and have led to the generation of new virus strains that are highly pathogenic in poultry. These new H5 HA containing viruses with their ability to evolve rapidly represent an unknown threat to humans in contact with infected poultry, and vaccination with an off-the-shelf vaccine may be impractical to provide protection to at-risk individuals. Instead, we have evaluated the efficacy of a formalin-inactivated vaccine, which could be derived directly from a circulating virus, to provide post-exposure protection. This strategy was evaluated using a prototypic highly pathogenic avian H5N1 strain, A/Vietnam/1203/2004, and demonstrated rapid induction of adaptive immune responses providing protection in a mammalian model of lethal infection. Additionally, this post-exposure vaccine was highly efficacious when administered 24 hours after exposure. This study offers a platform for developing effective post-exposure vaccines for treatment of highly virulent influenza infections. PMID- 27405489 TI - Tumor-associated mesenchymal stem cells inhibit naive T cell expansion by blocking cysteine export from dendritic cells. AB - Mesenchymal stem cells (MSCs) represent an important cellular constituent of the tumor microenvironment, which along with tumor cells themselves, serve to regulate protective immune responses in support of progressive disease. We report that tumor MSCs prevent the ability of dendritic cells (DC) to promote naive CD4(+) and CD8(+) T cell expansion, interferon gamma secretion and cytotoxicity against tumor cells, which are critical to immune-mediated tumor eradication. Notably, tumor MSCs fail to prevent DC-mediated early T cell activation events or the ability of responder T cells to produce IL-2. The immunoregulatory activity of tumor MSCs is IL-10- and STAT3-dependent, with STAT3 repressing DC expression of cystathionase, a critical enzyme that converts methionine-to-cysteine. Under cysteine-deficient priming conditions, naive T cells exhibit defective cellular metabolism and proliferation. Bioinformatics analyses as well as in vitro observations suggest that STAT3 may directly bind to a GAS-like motif within the cystathionase promoter (-269 to -261) leading to IL-10-STAT3 mediated repression of cystathionase gene transcription. Our collective results provide evidence for a novel mechanism of tumor MSC-mediated T cell inhibition within tumor microenvironment. PMID- 27405490 TI - Asymmetric synthesis of (-)-renieramycin T. AB - (-)-Renieramycin T, an interesting tetrahydroisoquinolinequinone alkaloid with a novel renieramycin-ecteinascidin mixed framework, is synthesized from the known phenol 16 in 22 steps with 6.2% overall yield. In the convergent route, the key cyclocondensation between the isoquinoline moiety 27 and trisubstituted phenylalaninol 14 is achieved with good selectivity to furnish bistetrahydroisoquinoline 29, which permits a rapid construction of the pentacyclic framework having a fully substituted aromatic A ring. PMID- 27405491 TI - Characterization and cytocompatibility of thermosensitive hydrogel embedded with chitosan nanoparticles for delivery of bone morphogenetic protein-2 plasmid DNA. AB - A novel injectable chitosan thermosensitive hydrogel was designed as a target multi-effect scaffold for endogenous repair of the periodontium. The hydrogel complex was designed by embedding chitosan nanoparticles (CSn) loaded with bone morphogenetic protein-2 plasmid DNA (pDNA-BMP2) into a chitosan (CS)-based hydrogel with alpha,beta-glycerophosphate (alpha,beta-GP), termed CS/CSn(pDNA BMP2)-GP. Characterization, the in vitro release profile for pDNA-BMP2, and cytocompatibility to human periodontal ligament cells (HPDLCs), were then conducted. The average diameter of the CSn(pDNA-BMP2) was 270.1 nm with a polydispersity index (PDI) of 0.486 and zeta potential of +27.0 mv. A DNase I protection assay showed that CSn could protect the pDNA-BMP2 from nuclease degradation. Encapsulation efficiency and loading capacity of CSn(pDNA-BMP2) were more than 80 and 30 %, respectively. The sol-gel transition time was only 3 min when CSn(pDNA-BMP2) was added into the CS/alpha,beta-GP system. Scanning electron microscopy showed that CSn(pDNA-BMP2) was randomly dispersed in a network with regular holes and a porous structure. Weighting method showed the swelling ratio and degradation was faster in medium of pH 4.0 than pH 6.8. An in vitro pDNA-BMP2 release test showed that the cumulative release rate of pDNA-BMP2 was much slower from CS/CSn-GP than from CSn in identical release media. In release media with different pH, pDNA-BMP2 release was much slower at pH 6.8 than at pH 4.0. Three dimensional culture with HPDLCs showed good cell proliferation and the Cell Counting Kit-8 assay indicated improved cell growth with the addition of CSn(pDNA BMP2) to CS/alpha,beta-GP. In summary, the CS/CSn(pDNA-BMP2)-GP complex system exhibited excellent biological properties and cytocompatibility, indicating great potential as a gene delivery carrier and tissue regeneration scaffold for endogenous repair of the periodontium. PMID- 27405492 TI - The outcome of endoscopy for recalcitrant greater trochanteric pain syndrome. AB - INTRODUCTION: Greater trochanteric pain syndrome (GTPS), previously referred as trochanteric bursitis, is a debilitating condition characterised by chronic lateral hip pain. The syndrome is thought to relate to gluteal tendinopathy, with most cases responding to non-operative treatment. A number of open and endoscopic surgical techniques targeting the iliotibial band, trochanteric bursa and gluteal tendons have, however, been described for severe recalcitrant cases. We report the outcomes of one such endoscopic approach here. MATERIALS AND METHODS: We retrospectively reviewed 49 patients (57 operations) who had undergone endoscopic longitudinal vertical iliotibial band release and trochanteric bursectomy. Inclusion criteria included diagnosed GTPS with a minimum of six months of non operative treatment. Exclusion criteria included concomitant intra- or extra articular hip pathology and previous hip surgery including total hip arthroplasty. Outcomes were assessed using the Visual Analogue Scale, Oxford hip Score and International Hip Outcome Tool (iHOT-33). RESULTS: The series included 42 females and 7 males with a mean age of 65.0 years (26.7-88.6). Mean follow-up time was 20.7 months (5.3-41.2). Eight patients had full thickness gluteal tendon tears, of which 7 were repaired. Adjuvant PRP was injected intraoperatively in 38 of 57 operations (67.2 %). At follow-up, overall mean Visual Analogue Scale values had decreased from 7.8 to 2.8 (p < 0.001), Oxford hip Scores had increased from 20.4 to 37.3 (p < 0.001) and iHOT-33 scores had increased from 23.8 to 70.2 (p < 0.001). Of the 57 operations performed, patients reported feeling very satisfied with the surgical outcome in 28 operations (49.1 %), satisfied in 17 operations (29.8 %) and less than satisfied in 12 operations (21.1 %). CONCLUSIONS: While the majority of patients with GTPS will improve with non operative management, endoscopic iliotibial band release, trochanteric bursectomy and gluteal tendon repair is a safe and effective treatment for severe recalcitrant cases. PMID- 27405493 TI - Accuracy of preoperative MRI in the diagnosis of subscapularis tears. AB - INTRODUCTION: The subscapularis has received little attention in the orthopedic literature, although such lesions are evident in up to 40 % of arthroscopies. An accurate diagnosis is important in clinical practice, as it affects both patient prognosis and surgical planning. The aim of this study was to evaluate the accuracy of preoperative MRI for the identification of subscapularis tears. Our secondary aim involved the identification of factors that may be predictive for the presence of subscapularis tears. MATERIALS AND METHODS: This retrospective case series included patients undergoing shoulder arthroscopy due to rotator cuff injury. MRI was performed using a 1.5 T unit, and the results were assessed by a musculoskeletal radiologist. The findings were compared to those of arthroscopic inspection. RESULTS: A total of 93 shoulders were analyzed. The overall accuracy was 82 %, with values of 79 % for partial tears and 89 % for full-thickness tears. Tears requiring repair demonstrated an accuracy of 88 %. Infraspinatus tears, fatty degeneration of the subscapularis, biceps instability and age were identified as predictive factors for the presence of injury. CONCLUSIONS: MRI of the shoulder demonstrated an accuracy of 82 % for the diagnosis of subscapularis tears. The accuracy values for partial and full-thickness tears were 79 and 89 %, respectively. LEVEL DE EVIDENCE: III, development of diagnostic criteria with universally applied reference-nonconsecutive patients. PMID- 27405494 TI - Ultrasound is as reliable as plain radiographs in the diagnosis of cam-type femoroacetabular impingement. AB - INTRODUCTION: In the diagnosis of femoroacetabular impingement (FAI), plain radiographs are accepted as the initial imaging method. However, there is no consensus regarding the optimal lateral view, and radiographs can underestimate the asphericity of the head-neck junction. Our research question was if ultrasound has at least the same reliability as X-ray and can be used as an alternative or additional method in the initial imaging of FAI. MATERIALS AND METHODS: Forty patients with a median age of 39 years were consecutively included after diagnosis of cam-type FAI on magnetic resonance imaging (MRI). All patients underwent radiography involving a plain anteroposterior-view, frog-leg lateral view, and ultrasound of the hip joint in the ventral longitudinal section at 20 degrees internal rotation. Parameters measured by MRI, radiographs, and ultrasound were the alpha angle, anterior offset, offset ratio, and anterior femoral distance. RESULTS: No significant difference between the alpha angle on MRI (64.8 degrees ), the frog-leg view (66.3 degrees ), or ultrasound (65.6 degrees ) could be detected. Comparable correlation was found between the alpha angle on MRI and the frog-leg lateral view (r = 0.73; p < 0.0001) and between the alpha angle on MRI and sonograms (r = 0.77; p < 0.0001). The intra-class correlation coefficient for measurements using ultrasound was 0.81-0.98, and using radiographs was 0.83-0.99, with the exception of measurements involving the anterior offset on the frog-leg lateral view (0.61 and 0.64). CONCLUSIONS: Ultrasound is as reliable as plain radiographs in the diagnosis of cam-type FAI and can serve as an alternative or additional method in initial imaging. PMID- 27405496 TI - Polymorphisms in complement genes and risk of preeclampsia in Taiyuan, China. AB - BACKGROUND AND OBJECTIVES: Altered immune response may be a part of the pathogenesis of preeclampsia. The few epidemiologic studies that have investigated the associations between genetic variations in the complement system genes and preeclampsia risk have reached inconsistent results. The aim of this study is to determine if polymorphisms in the complement system genes could influence the risk of preeclampsia. METHODS: We examined 51 SNPs in the C3, C5, C6, MASP1, MBL2 and CD55 genes and the risk of preeclampsia and its clinical subtypes in a nested case-control study of 203 preeclampsia cases and 233 controls. RESULTS: Both C6 and MASP1 were associated with the risk of preeclampsia. C6 (rs7444800, rs4957381) and MASP1 (rs1108450, rs3774282, rs698106) polymorphisms were associated with the risk of early-onset preeclampsia and severe preeclampsia, while MASP1 (rs1357134, rs698090) polymorphisms were associated with the risk of late-onset preeclampsia and severe preeclampsia. CONCLUSIONS: Our study provided novel evidence that genetic variations in complement genes C6 and MASP1were associated with preeclampsia risk, and that the risk varied by preeclampsia subtypes. PMID- 27405497 TI - Are Non-steroidal Anti-Inflammatory Drugs Clinically Suitable for the Treatment of Symptoms in Depression-Associated Inflammation? AB - The aetiology and pathophysiology of depression have long been associated with inflammation, at least in a proportion of patients. Altered cytokine activity in the periphery and in the brain has brought support to a concept of depression associated inflammation. However, these immunological changes - and inflammation in particular - in depression have only been recently targeted for treatment. Non steroidal anti-inflammatory drugs (NSAIDs) have been proposed to be of clinical use in the treatment of depression either as monotherapy or as adjuncts in combination with antidepressants. Specifically, selective cyclooxygenase (COX)-2 and non-selective COX inhibitor NSAIDs as adjuncts or monotherapy have been trialled clinically. A limited body of clinical research has been conducted with mixed results so far. Although meta-analyses appear to support the use of NSAIDs in acute depression, the overall effect is mainly biased by the effects of celecoxib for which the best evidence exists to date. Efficacy data of non selective COX inhibitor NSAIDs on depressive symptoms is limited and out of six studies, only a retrospective analysis shows positive results for non-selective COX inhibitor. Clinical data on aspirin, an irreversible inhibitor of both COX-1 and COX-2, are mainly experimental and hypothetical at this stage, but may be promising in depressed patients with concomitant inflammatory conditions. The main problematic factor is that current evidence rests on trials in acute depression. Because of the dynamic nature of depression, it is important exploring if NSAIDs and other anti-inflammatory treatments may have a preventive role in early stages of depression and for relapse prevention. The possible impact of anti-inflammatory treatments on immune changes in different phases of depression warrants caution for a wide and preventive use of anti-inflammatory agents in depression-associated inflammation. PMID- 27405507 TI - Simultaneous Determination of a Fixed-Dose Combination of Lercanidipine and Valsartan in Human Plasma by LC-MS-MS: Application to a Pharmacokinetic Study. AB - A simple, sensitive and reproducible liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the first time for simultaneous quantification of lercanidipine and valsartan in human plasma. The analytes were extracted by simple protein precipitation with acetonitrile and separated on a Hanbon Hedera ODS-2 C18 (150 mm* 2.1 mm, 5 MUm) column. The mobile phase was composed of a mixture (53:47, v/v) of acetonitrile and 10 mmol/L ammonium acetate containing 0.5% formic acid. The analytes were ionized by positive electrospray ion and detected in the multi-reaction monitoring mode with m/z 612.1 -> 280.2 for lercanidipine, m/z 436.0 -> 235.1 for valsartan and m/z 285.1 -> 193.1 for diazepam, the internal standard. The calibration curves obtained were linear over the concentration range of 0.01504 10.07 ng/mL for lercanidipine and 5.025-6,030 ng/mL for valsartan. The results of the intra- and inter-day precision studies were within the acceptance range. The recoveries of the analytes were in the range of 98-103%. This method was successfully applied to the pharmacokinetic study of a novel fixed-dose combination of lercanidipine and valsartan formulation after an oral administration to healthy Chinese subjects. PMID- 27405506 TI - Treatment with Rhodiola crenulata root extract ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular fatty acid translocase/CD36 redistribution in skeletal muscle. AB - BACKGROUND: Rhodiola species have been used for asthenia, depression, fatigue, poor work performance and cardiovascular diseases, all of which may be associated with insulin resistance. To disclose the underlying mechanisms of action, the effect of Rhodiola crenulata root (RCR) on insulin resistance was investigated. METHODS: Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. The indexes of lipid and glucose homeostasis were determined enzymatically and/or by ELISA. Gene expression was analyzed by Real-time PCR, Western blot and/or confocal immunofluorescence. RESULTS: RCR extract (50 mg/kg) suppressed fructose-induced hyperinsulinemia and the increases in the homeostasis model assessment of insulin resistance index and the adipose tissue insulin resistance index in rats. Additionally, this treatment had a trend to restore the ratios of glucose to insulin and non-esterified fatty acids (NEFA) to insulin. Mechanistically, RCR suppressed fructose-induced acceleration of the clearance of plasma NEFA during oral glucose tolerance test (OGTT), and decreased triglyceride content and Oil Red O staining area in the gastrocnemius. Furthermore, RCR restored fructose-induced sarcolemmal overexpression and intracellular less distribution of fatty acid translocase/CD36 that contributes to etiology of insulin resistance by facilitating fatty acid uptake. CONCLUSION: These results suggest that RCR ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle. Our findings may provide a better understanding of the traditional use of Rhodila species. PMID- 27405508 TI - Metal-Organic Framework [Cd(LTP)2]n for Improved Enantioseparations on a Chiral Cyclodextrin Stationary Phase in GC. AB - Metal-organic frameworks (MOFs) are a class of novel porous materials consisting of clusters or chains of metal ions and organic linkers. The chiral MOF [Cd(LTP)2]n (LTP = l(-)-thiazolidine-4-carboxylic acid) possesses infinite extension three-dimensional supramolecular reticular structure with right-handed helix. In this work, three capillary columns (A, B and C) containing MOF [Cd(LTP)2]n, permethylated beta-cyclodextrin (CD) and sodium chloride, and MOF [Cd(LTP)2]n and permethylated beta-CD, respectively, have been prepared and their respective enantioseparation abilities have been investigated. The polarities of all of the MOFs and permethylated beta-CDs are moderate. The numbers of theoretical plates (plate m-1) of the three columns have been measured using n dodecane at 120 degrees C, which followed an increasing order of A (3100) < B (3800) < C (4300). Some racemates were separated with different resolutions on Columns A, B and C. The results indicated that the incorporated MOF [Cd(LTP)2]n enhanced the separations of racemates on a permethylated beta-CD stationary phase with high column efficiency and good reproducibility in gas chromatography. PMID- 27405509 TI - Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. AB - OBJECTIVE: To investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: In 13 310 patients with RA observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure. RESULTS: 37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/cumulative glucocorticoids and non steroidal anti-inflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2-0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-alpha inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment. CONCLUSIONS: The incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation. PMID- 27405510 TI - From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease. AB - Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the 'obesity paradox', but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a 'healthy', protective adipose tissue phenotype. (c) 2016 World Obesity. PMID- 27405511 TI - Artificial Dense Granules: A Procoagulant Liposomal Formulation Modeled after Platelet Polyphosphate Storage Pools. AB - Granular platelet-sized polyphosphate nanoparticles (polyP NPs) were encapsulated in sterically stabilized liposomes, forming a potential, targeted procoagulant nanotherapy resembling human platelet dense granules in both structure and functionality. Dynamic light scattering (DLS) measurements reveal that artificial dense granules (ADGs) are colloidally stable and that the granular polyP NPs are encapsulated at high efficiencies. High-resolution scanning transmission electron microscopy (HR-STEM) indicates that the ADGs are monodisperse particles with a 150 nm diameter dense core consisting of P, Ca, and O surrounded by a corrugated 25 nm thick shell containing P, C, and O. Further, the ADGs manifest promising procoagulant activity: Detergent solubilization by Tween 20 or digestion of the lipid envelope by phospholipase C (PLC) allows for ADGs to trigger autoactivation of Factor XII (FXII), the first proteolytic step in the activation of the contact pathway of clotting. Moreover, ADGs' ability to reduce the clotting time of human plasma in the presence of PLC further demonstrate the feasibility to develop ADGs into a potential procoagulant nanomedicine. PMID- 27405512 TI - Predictors of Participation in the Family Check-Up Program: a Randomized Trial of Yearly Services from Age 2 to 10 Years. AB - A key challenge of community-based prevention programs is engaging families in the context of services settings involving children and families. The Family Check-Up (FCU) program is designed to engage families in parenting support appropriate to their level of need by use of assessment-enhanced motivational interviewing. This study involved families screened for risk who were seeking services at women, infant, and children's offices in three geographical regions (N = 731). Families in the randomized intervention group (N = 367) were offered the FCU yearly, from age 2 through 10. The results of multivariate modeling indicated that caregivers reporting high levels of perceived caregiving stress (i.e., depression, low parenting satisfaction, daily hassles) participated at a higher rate in two critical components (feedback and follow-up support interventions) of the FCU program over the 8-year trial period than caregivers reporting lesser degrees of stress. The implications of these findings are discussed in the context of family-centered programs for the prevention of child behavior problems and directions for future research. PMID- 27405514 TI - Eliminated Phototoxicity of TiO2 Particles by an Atomic-Layer-Deposited Al2 O3 Coating Layer for UV-Protection Applications. AB - We demonstrate the conformal coating of an ultrathin Al2 O3 layer on TiO2 nanoparticles through atomic layer deposition by using a specifically designed rotary reactor to eliminate the phototoxicity of the particles for cosmetic use. The ALD reactor is modified to improve the coating efficiency as well as the agitation of the particles for conformal coating. Elemental and microstructural analyses show that ultrathin Al2 O3 layers are conformally deposited on the TiO2 nanoparticles with a controlled thickness. Rhodamine B dye molecules on Al2 O3 coated TiO2 exhibited a long life time under UV irradiation, that is, more than 2 h, compared to that on bare TiO2 , that is, 8 min, indicating mitigation of photocatalytic activity by the coated layer. The effect of carbon impurities in the film resulting from various deposition temperatures and thicknesses of the Al2 O3 layer on the photocatalytic activity are also thoroughly investigated with controlled experimental condition by using dye molecules on the surface. Our results reveal that an increased carbon impurity resulting from a low processing temperature provides a charge conduction path and generates reactive oxygen species causing the degradation of dye molecule. A thin coated layer, that is, less than 3 nm, also induced the tunneling of electrons and holes to the surface, hence oxidizing dye molecules. Furthermore, the introduction of an Al2 O3 layer on TiO2 improves the light trapping thus, enhances the UV absorption. PMID- 27405513 TI - The value of circulating CYFRA21-1 expression in patients with nasopharyngeal carcinoma: a study of 529 subjects. AB - BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) needs more reliable biomarkers. The aim of this study was to investigate serum cytokeratin 19 fragment 21.1 (CYFRA21-1) as an NPC biomarker based on data from a large sample. METHODS: From October 2010 to February 2014, 529 subjects were enrolled and divided into three groups-NPC group (n = 274), healthy control group (n = 175) and nasal inflammatory disease group (n = 80). Serum CYFRA21-1 levels were measured prior to radiotherapy/chemoradiotherapy, and their associations with T, N, and clinical classification were determined. Receiver operating characteristic curve analysis was performed to discriminate the NPC group from the healthy control and nasal inflammatory disease groups. Three Epstein-Barr virus (EBV) antibodies and their correlations with serum CYFRA21-1 levels were analyzed. RESULTS: Pretreatment serum CYFRA21-1 levels were significantly elevated in the NPC group compared with the other groups (p < 0.01), Furthermore, serum CYFRA21-1 levels decreased significantly after radiotherapy (p < 0.01). Serum CYFRA21-1 levels were closely related to T, N, and clinical classifications. The area under the curve, sensitivity and specificity of the serum CYFRA21-1 levels in the NPC patients were 0.89, 0.87 and 0.83, respectively. Strong correlations were observed between serum CYFRA21-1 levels and EBV antibodies. CONCLUSION: Serum CYFRA21-1 may be a reliable and effective biomarker for NPC. PMID- 27405515 TI - Role of microRNA508-3p in melanogenesis by targeting microphthalmia transcription factor in melanocytes of alpaca. AB - It has been demonstrated that microRNAs (miRNAs) play important roles in the control of melanogenesis and hair color in mammals. By comparing miRNA expression profiles between brown and white alpaca skin, we previously identified miR508-3p as a differentially expressed miRNA suggesting its potential role in melanogenesis and hair color formation. The present study was conducted to determine the role of miR508-3p in melanogenesis in alpaca melanocytes. In situ hybridization showed that miR508-3p is abundantly present in the cytoplasma of alpaca melanocytes. miR508-3p was predicted to target the gene encoding microphthalmia transcription factor (MITF) and a luciferase reporter assay indicated that miR508-3p regulates MITF expression by directly targeting its 3'UTR. Overexpression of miR508-3p in alpaca melanocytes down-regulated MITF expression both at the messenger RNA and protein level and resulted in decreased expression of key melanogenic genes including tyrosinase and tyrosinase-related protein 2. Overexpression of miR508-3p in melanocytes also resulted in decreased melanin production including total alkali-soluble melanogenesis, eumelanogenesis and pheomelanogenesis. Results support a functional role of miR508-3p in regulating melanogenesis in alpaca melanocytes by directly targeting MITF. PMID- 27405516 TI - Long-term effects of soil management on ecosystem services and soil loss estimation in olive grove top soils. AB - Soil management has important effects on soil properties, runoff, soil losses and soil quality. Traditional olive grove (OG) management is based on reduced tree density, canopy size shaped by pruning and weed control by ploughing. In addition, over the last several decades, herbicide use has been introduced into conventional OG management. These management strategies cause the soil surface to be almost bare and subsequently high erosion rates take place. To avoid these high erosion rates several soil management strategies can be applied. In this study, three strategies were assessed in OG with conventional tillage in three plots of 1ha each. Soil properties were measured and soil erosion rates were estimated by means of the RUSLE model. One plot was managed with no amendments (control), and the other two were treated with olive leaves mulch and oil mill pomace applied yearly from 2003 until 2013. The control plot experienced the greatest soil loss while the use of olive leaves as mulch and olive mill pomace as an amendment resulted in a soil loss reduction of 89.4% and 65.4% respectively (assuming a 5% slope). In addition, the chemical and physical soil properties were improved with the amendments. This combined effect will created a higher quality soil over the long term that it is more resilient to erosion and can provide better ecosystem services, as its functions are improved. PMID- 27405517 TI - Emissions of PCDD/Fs, PBDD/Fs, dioxin like-PCBs and PAHs from a cement plant using a long-term monitoring system. AB - The aim of the present work was to assess the emission of different persistent organic pollutants from a cement plant over a period of one year, under normal operational conditions. Thus, a long-term sampling device was installed in the clinker kiln stack of the cement plant. The factory uses petroleum coke as primary fuel, but also alternative fuels such as solid recovered fuel (SRF), automotive shredder residue (ASR), sewage sludge, waste tires, and meat and bone meal (MBM) wastes, with an energy substitution level of about 40%. Both PCDD/Fs (together with dl-PCBs) and PBDD/Fs were continuously sampled, with a total of ten samples collected in 2-4week periods. Also, PAHs were sampled during one-week periods, in order to evaluate their emissions in three different samples. The emission levels throughout the year were much lower than the set legal limits in all substances, being <10pgI-TEQ/Nm(3) in the case of PCDD/Fs. The data obtained allowed calculation of updated emission factors for the cement sector, which were 8.5ng I-TEQ/ton clinker for PCDD/Fs and 3.2ng WHO-TEQ/ton clinker for PCBs. With respect to the congener distribution, 2,3,7,8-TCDF accounts for 60 to 68% of the total toxicity for PCDD/Fs, and in PBDD/F emissions, a clear predominance of octa substituted species (both dioxin and furan) was found. PMID- 27405518 TI - Co-transport of Pb(2+) and TiO2 nanoparticles in repacked homogeneous soil columns under saturation condition: Effect of ionic strength and fulvic acid. AB - This study investigated the effects of suspended TiO2 nanoparticles (nTiO2) on the transport of Pb(2+) in saturated repacked soil columns under different ionic strengths (IS) and in the presence of fulvic acid (FA). Also, the contribution of soil colloids to the mobility of Pb(2+) was discussed. In the absence of nTiO2, little amount of Pb(2+) was detected in the effluent even in the presence of FA. However, the presence of nTiO2 significantly enhanced the mobility of Pb(2+) in soil columns under all tested conditions and nTiO2-associated Pb(2+) was the major migration species of Pb(2+). Increasing the solution IS decreased the nTiO2 associated Pb(2+) migration due to the significant decrease in the mobility of nTiO2 in soil. FA remarkably increased the nTiO2-associated Pb(2+) mobility in soil column, which was mainly to increase the mobility of nTiO2 in soil and decrease desorption rate of Pb(2+) from nTiO2 during transport. Moreover, nTiO2 significantly enhanced the release of Fe-Al soil colloids, which in turn was also responsible for the enhancement of Pb(2+) mobility in soil. PMID- 27405519 TI - The Water Footprint as an indicator of environmental sustainability in water use at the river basin level. AB - One of the main challenges in water management is to determine how the current water use can condition its availability to future generations and hence its sustainability. This study proposes the use of the Water Footprint (WF) indicator to assess the environmental sustainability in water resources management at the river basin level. The current study presents the methodology developed and applies it to a case study. The WF is a relatively new indicator that measures the total volume of freshwater that is used as a production factor. Its application is ever growing in the evaluation of water use in production processes. The calculation of the WF involves water resources (blue), precipitation stored in the soil (green) and pollution (grey). It provides a comprehensive assessment of the environmental sustainability of water use in a river basin. The methodology is based upon the simulation of the anthropised water cycle, which is conducted by combining a hydrological model and a decision support system. The methodology allows the assessment of the environmental sustainability of water management at different levels, and/or ex-ante analysis of how the decisions made in water planning process affect sustainability. The sustainability study was carried out in the Segura River Basin (SRB) in South eastern Spain. The SRB is among the most complex basins in Europe, given its special peculiarities: competition for the use, overexploitation of aquifers, pollution, alternative sources, among others. The results indicate that blue water use is not sustainable due to the generalised overexploitation of aquifers. They also reveal that surface water pollution, which is not sustainable, is mainly caused by phosphate concentrations. The assessment of future scenarios reveals that these problems will worsen if no additional measures are implemented, and therefore the water management in the SRB is environmentally unsustainable in both the short- and medium-term. PMID- 27405520 TI - Back-trajectory modelling and DNA-based species-specific detection methods allow tracking of fungal spore transport in air masses. AB - Recent advances in molecular detection of living organisms facilitate the introduction of novel methods to studies of the transport of fungal spores over large distances. Monitoring the migration of airborne fungi using microscope based spore identification is limited when different species produce very similar spores. In our study, DNA-based monitoring with the use of species-specific probes allowed us to track the aerial movements of two important fungal pathogens of oilseed rape (Brassica napus L.), i.e., Leptosphaeria maculans and Leptosphaeria biglobosa, which have identical spore shape and size. The fungi were identified using dual-labelled fluorescent probes that were targeted to a beta-tubulin gene fragment of either Leptosphaeria species. Spore identification by Real-Time PCR techniques capable of detecting minute amounts of DNA of selected fungal species was combined with back-trajectory analysis, allowing the tracking of past movements of air masses using the Hybrid Single Particle Lagrangian Integrated Trajectory model. Over a study period spanning the previous decade (2006-2015) we investigated two specific events relating to the long distance transport of Leptosphaeria spp. spores to Szczecin in North-West Poland. Based on the above mentioned methods and the results obtained with the additional spore sampler located in nearby Szczecin, and operating at the ground level in an oilseed rape field, we have demonstrated that on both occasions the L. biglobosa spores originated from the Jutland Peninsula. This is the first successful attempt to combine analysis of back-trajectories of air masses with DNA-based identification of economically important pathogens of oilseed rape in Europe. In our studies, the timing of L. biglobosa ascospore dispersal in the air was unlikely to result in the infection of winter oilseed rape grown as a crop plant. However, the fungus could infect other host plants, such as vegetable brassicas, cruciferous weeds, spring rapeseed and winter rapeseed growing as a volunteer plant. PMID- 27405521 TI - Genetic heterogeneity of platelet glycoproteins Ia and IIIa and the risk of spontaneous miscarriages. AB - OBJECTIVE: The aim of this study was to investigate the association between the genetic heterogeneity of platelet glycoproteins Ia (GpIa-C807T) and IIIa (GpIIIa PlA1/PlA2) and spontaneous abortions. STUDY DESIGN: Two hundred and twenty two women with a history of unexplained spontaneous miscarriages and no successful pregnancy, and 60 fertile women serving as controls were genotyped for the GpIa C807T and GpIIIa-PlA1/PlA2 polymorphisms by pyrosequencing. RESULTS: In comparison with the common alleles homozygotes, GpIa-807T and GpIIIa-PlA2 carriers had an increased risk of fetal loss (OR = 3.36, 95%CI: 1.85-6.11, p < 0.001, and OR = 2.58, 95%CI: 1.30-5.13, p = 0.006, respectively). For subjects who were combined carriers of the GpIa-807T and GpIIIa-PlA2 alleles, the risk increased further (OR = 9.13, 95%CI: 2.99-27.82, p < 0.001). The above ORs were highest for women who were younger than 30 years of age. CONCLUSIONS: The GpIa C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly their combination are associated with increased risk of spontaneous abortions. The correlations were stronger for younger patients. Our results indicate that GpIa-807T and GpIIIa-PlA2 are susceptibility alleles for fetal loss in the Greek population. PMID- 27405523 TI - The Deckled Incision: Study Protocol for a Randomized Controlled Trial. AB - BACKGROUND: Scar visibility is multifactorial and skin closure technique is thought to play an important role. It is an established principle in plastic surgery that Z plasties generally reduce scar contracture by breaking up the lines of tension in a wound. As an extension of this principle, it is postulated that irregular "deckled" skin incisions made during tumor excision would produce aesthetically superior scars. OBJECTIVE: The primary objective of this study is to assess both the clinician and patient opinion of scar quality using the Patient and Observer Scar Assessment Scale (POSAS). Secondary objectives include the proportion of scars judged as good by the both the patient and clinician (less than or equal to 5 on the overall PSOAS scale), the number of adverse events, and the proportion of the scar visible at 1 meter. METHODS: The deckling study will be a patient-blinded, simple randomized controlled trial (RCT) at a single center institution. The two groups will be equally allocated on a 1:1 ratio into the control and treatment arms. All patients greater than 18 years of age undergoing a plastic surgery procedure involving excision of skin lesions will be enrolled. Any patients requiring re-excision through the wound or undergoing injectable corticosteroid therapy will be excluded. A total of 500 patients will be enrolled. The patients will be followed-up at 1 week, 3 months, and 6 months post-operatively. RESULTS: The study is expected to begin enrolment in August 2016. We anticipate that the deckling study group will have superior scar outcomes when compared to the straight line incision. From clinical experience this is especially true for lesions involving the face and in those areas of the skin that have undergone radiation therapy. The study will be funded by the Plastics and Reconstructive Surgery Department at St Vincent's Hospital, Sydney, Australia. Ethics approval has been obtained for the study. CONCLUSION: We believe this will be an important study to assess a novel method to improve the appearance of post-operative scars. The deckling study is simple to master, can be applicable to almost any surgical procedure, and can have good generalizability to a large population cohort. CONCLUSIONS: We believe this will be an important study to assess a novel method to improve the appearance of post operative scars. The deckling study is simple to master, can be applicable to almost any surgical procedure, and can have good generalizability to a large population cohort. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616000193471; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261600019347 (Archived by Webcite at http://www.webcitation.org/6gmG8yf1A). PMID- 27405524 TI - Management of the Chronic Leukemias: Special Considerations in the Elderly Patient. Part I. Chronic Lymphocytic Leukemias. PMID- 27405525 TI - Acute Colonic Graft-versus-host Disease and Ulcerative Colitis with Respect to Cytokines. AB - Colonic graft-versus-host disease (GVHD) occurring after allogeneic bone marrow transplantation (BMT) resembles ulcerative colitis (UC) with respect to pathological features. In addition, therapy for UC has been reported to be effective for the treatment of refractory GVHD. The relationship of these two conditions with respect to cytokines was investigated in the present study. Among 27 patients who underwent allogeneic BMT during the previous two years, six developed GVHD of grade 3 or higher, and these six patients were compared with the other 21 patients. In six patients, the levels of the following cytokines were significantly elevated at the onset of GVHD: tumor necrosis factor-alpha (p<0.05), interleukin-6 (p<0.05), interleukin-8 (p<0.01), interferon-gamma (p<0.05), and interleukin-7 (p<0.0001). These findings indicate that GVHD and UC are similar in terms of their cytokine profile. PMID- 27405526 TI - Different Mechanisms of Resistance to Lymphokine-activated Killer (LAK) Cells in Leukemic Cell Sublines Selected by Etoposide or by LAK Cells. AB - Two models of in vitro induction of human IM-9 lymphoblastoid cell line resistance to LAK cell-mediated killing were compared. IM-9 cell line variants were selected in vitro by prolonged exposure to LAK cells or to etoposide. Sensitivity to killing by LAK cells or by etoposide, conjugation with LAK cells and surface marker patterns were compared. Both LAK-cell-selected cell subline (IM-9/SL-15) and etoposide-selected cell subline (IM-9/ER) have acquired resistance to LAK cell-mediated death. IM-9/ER cells, but not IM-9/SL-15 cells, were 3.2-fold less sensitive to etoposide as compared to parental IM-9 cells. IM 9/SL-15 cells revealed decreased conjugation with LAK cells and augmented CDlla/CD18 surface molecule expression as compared to IM-9 line. In contrast, IM 9/ER cells displayed a level of conjugation with LAK cells equal to IM-9 cells, but loss of CD11a/C18 expression. Our results suggest different mechanisms of acquired resistance to LAK cells are operative in etoposide- or LAK-selected sublines, involving deterioration of LFA-1 molecule expression and altered conjugation properties, respectively. PMID- 27405522 TI - Mentalization-based treatment in groups for adolescents with borderline personality disorder (BPD) or subthreshold BPD versus treatment as usual (M-GAB): study protocol for a randomized controlled trial. AB - BACKGROUND: Evidence-based outpatient psychotherapeutic programs are first-line treatment of borderline personality disorder (BPD). Early and effective treatment of BPD is crucial to the prevention of its individual, psychosocial, and economic consequences. However, in spite of recent advantages in diagnosing adolescent BPD, there is a lack of cost-effective evidence-based treatment programs for adolescents. Mentalization-based treatment is an evidence-based program for BPD, originally developed for adults. METHODS/DESIGN: AIMS/HYPOTHESES: We will investigate whether a specifically designed mentalization-based treatment in groups is an efficacious treatment for adolescents with BPD or subthreshold BPD compared to treatment as usual. The trial is a four-center, two-armed, parallel group, assessor-blinded randomized clinical superiority trial. One hundred twelve patients aged 14 to 17 referred to Child and Adolescent Psychiatric Clinics in Region Zealand are randomized to 1 year of either mentalization-based treatment in groups or treatment as usual. Patients will be included if they meet at least four DSM-5 criteria for BPD. The primary outcome is self-reported borderline features at discharge. Secondary outcomes will include self-harm, depression, BPD criteria, externalizing and internalizing symptoms, and social functioning, together with parental reports on borderline features, externalizing and internalizing symptoms. Measures of attachment and mentalization will be included as mediational variables. Follow-up assessment will take place at 3 and 12 months after end of treatment. DISCUSSION: This is the first randomized controlled trial to test the efficacy of a group-based mentalization-based treatment for adolescents with BPD or subthreshold BPD. If the results confirm our hypothesis, this trial will add to the treatment options of cost-effective treatment of adolescent BPD. TRIAL REGISTRATION: Clinicaltrials.gov NCT02068326 , February 19, 2014. PMID- 27405527 TI - Hepatosplenic Candidiasis, its Treatment and Effect on Remission Status in Patients with Acute Leukaemia-a Report of Five Cases. AB - Hepatosplenic candidiasis is an increasingly encountered complication of treatment of patients with acute leukaemia [[1] Clin. Infect. Dis. 24 (1997) 375]. Management is difficult as delay in further chemotherapy may allow relapse of the leukaemia while the infection may progress if chemotherapy is continued [[2] Anticancer Res. 19 (1999) 757]. We report five cases of suspected hepatosplenic candidiasis in a single haematology unit over a 30-month period. All patients were treated with oral fluconazole following intravenous amphotericin or liposomal amphotericin B lipid complex. Chemotherapy was withheld during treatment of infection. Two patients remain in haematological remission despite suboptimal therapy for their leukaemia. One patient died from progressive fungal infection, 1 patient of cardiac disease and 1 patient has had recent relapse of their leukaemia. We demonstrate that hepatosplenic candidiasis may be treated with oral fluconazole while chemotherapy is discontinued and also suggest that this infection or its treatment may have had a beneficial immunomodulatory affect on the leukaemic process in the surviving patients. PMID- 27405528 TI - Nocardiosis Causing Hypocellular Bone Marrow after Allogeneic Peripheral Blood Stem Cell Transplantation. AB - Nocardia infection is rare in bone marrow transplant (BMT) recipients with less than 30 cases reported in the literature [1-4]. The majority of the cases occurred late in the post-transplant period. Common clinical presentations included formation of widespread and multiple abscesses. Bone marrow hypoplasia is an uncommon finding. We describe the first case of nocardiosis, diagnosed at day 100 after non-myeloablative allogeneic peripheral blood stem cell transplantation, presenting as pancytopenia and hypocellular marrow. Eradication of the infection with antibiotics resulted in complete hematological recovery. PMID- 27405529 TI - Prevention of Bleeding Complications in Neonates With Liver Failure Undergoing Surgery Using Recombinant Factor VIIa. AB - Recombinant factor Vila [rFVIIa (Novoseven(r), Novo Nordisk, Bagsvaerd, Denmark)] is a novel therapy used to treat hemophiliacs with inhibitors and bleeding. Coagulopathy with severe factor VII deficiency is common in liver failure, and liver biopsies are often required in these patients; however, there is a high risk of bleeding complications. In one report, 12.5% of children with coagulopathy and 0.8% of children without coagulopathy had bleeding complications after liver biopsy. Other reports have demonstrated increased bleeding after liver biopsy in patients with bleeding disorders. Standard treatment for such patients includes fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC), both of which have significant limitations. In order to achieve hemostatic factor levels, large volumes of FFP are required which may not be tolerated, especially in young children and patients with liver failure. PCC can cause DIC, especially in liver failure and carry a risk of viral transmission. We have performed liver biopsies and central venous catheter (CVC) placement in three neonates with liver failure utilizing rFVIIa to prevent bleeding complications. All three patients had mild gastrointestinal (GI) bleeding prior to surgery which did not respond to FFP and cryoprecipitate (cryo). None of the patients had bleeding complications. These cases demonstrate the utility of using rFVIIa in neonates with liver failure undergoing liver biopsy and CVC placement. Our choice of rFVIIa rather than PCC was based on selecting an agent that targets the deficiency of factor VII, concerns for disseminated intravascular coagulation, and the risk of transmitting infectious agents from plasma products. In conclusion, we recommend the use of rFVIIa for prevention of bleeding complications prior to surgery in patients with liver failure. PMID- 27405530 TI - Thrombophilic DNA Mutations As Independent Risk Factors for Stroke and Avascular Necrosis in Sickle Cell Anemia. AB - Thrombosis may be important in the pathophysiology of certain complications of sickle cell anemia (SCA), including cerebrovascular accident (CVA, stroke) and avascular necrosis (AVN). No single laboratory or clinical parameter can accurately identify patients who will develop these thrombotic complications. We hypothesized that a subset of patients with SCA have genetic thrombophilic mutations that increase the risk of stroke or AVN. We examined nine known thrombophilic DNA polymorphisms in alpha-fibrinogen, beta-fibrinogen, platelet glycoprotein IIIa, Factor VII, methylenetetra-hydrofolate reductase, plasminogen activator inhibitor-1, prothrombin, and Factor V genes in 101 African-American patients with SCA (27 CVA, 16 AVN). The allele frequency of thrombophilic mutations ranged from 0.0 (Prothrombin, Factor V) to 0.33 (alpha-fibrinogen). No mutation was significantly more common in patients with CVA or AVN than in patients without these complications. These nine thrombophilic mutations do not appear to be significant risk factors for the development of clinically overt CVA or AVN in SCA. PMID- 27405533 TI - Knodle: A Support Vector Machines-Based Automatic Perception of Organic Molecules from 3D Coordinates. AB - Here we address the problem of the assignment of atom types and bond orders in low molecular weight compounds. For this purpose, we have developed a prediction model based on nonlinear Support Vector Machines (SVM), implemented in a KNOwledge-Driven Ligand Extractor called Knodle, a software library for the recognition of atomic types, hybridization states, and bond orders in the structures of small molecules. We trained the model using an excessive amount of structural data collected from the PDBbindCN database. Accuracy of the results and the running time of our method is comparable with other popular methods, such as NAOMI, fconv, and I-interpret. On the popular Labute's benchmark set consisting of 179 protein-ligand complexes, Knodle makes five to six perception errors, NAOMI makes seven errors, I-interpret makes nine errors, and fconv makes 13 errors. On a larger set of 3,000 protein-ligand structures collected from the PDBBindCN general data set (v2014), Knodle and NAOMI have a comparable accuracy of approximately 3.9% and 4.7% of errors, I-interpret made 6.0% of errors, while fconv produced approximately 12.8% of errors. On a more general set of 332,974 entries collected from the Ligand Expo database, Knodle made 4.5% of errors. Overall, our study demonstrates the efficiency and robustness of nonlinear SVM in structure perception tasks. Knodle is available at https://team.inria.fr/nano d/software/Knodle . PMID- 27405532 TI - Advances in mapping malaria for elimination: fine resolution modelling of Plasmodium falciparum incidence. AB - The long-term goal of the global effort to tackle malaria is national and regional elimination and eventually eradication. Fine scale multi-temporal mapping in low malaria transmission settings remains a challenge and the World Health Organisation propose use of surveillance in elimination settings. Here, we show how malaria incidence can be modelled at a fine spatial and temporal resolution from health facility data to help focus surveillance and control to population not attending health facilities. Using Namibia as a case study, we predicted the incidence of malaria, via a Bayesian spatio-temporal model, at a fine spatial resolution from parasitologically confirmed malaria cases and incorporated metrics on healthcare use as well as measures of uncertainty associated with incidence predictions. We then combined the incidence estimates with population maps to estimate clinical burdens and show the benefits of such mapping to identifying areas and seasons that can be targeted for improved surveillance and interventions. Fine spatial resolution maps produced using this approach were then used to target resources to specific local populations, and to specific months of the season. This remote targeting can be especially effective where the population distribution is sparse and further surveillance can be limited to specific local areas. PMID- 27405535 TI - Synthesis and fluxional behaviour of novel chloroborole dimers. AB - The (B-Cl)-chloroboroles 2-chloro-1,3-di(4-R-phenyl)-2,4,5,6-tetra hydrocyclopenta[c]borole (R = H, Br) undergo a novel dimerisation process in CH2Cl2 solution. The resulting unsymmetric dimers are highly fluxional in solution via reversible enantiomerisation through an intermediate with mirror symmetry. DFT calculations suggest an unusual dimerisation mechanism and provide insight into the dynamics of the dimers. PMID- 27405536 TI - Effect of foodstuff on muscle forces during biting off. AB - PURPOSE: The subject of this research is the human stomatognathic system and the process of biting off various foodstuffs. METHODS: The research was divided into two stages - an experimental stage and a computational stage. In the first stage, tests were carried out to determine the force-displacement characteristics for the biting off food. For this purpose five different foodstuffs were tested in a testing machine and their strength characteristics were determined. The aim of the second stage was to build a computational model of the human cranium-mandible system and to run simulations of the process of biting off food in order to determine the muscular forces as a function of the food. A kinematic scheme was developed on the basis of a survey of the literature on the subject and used to create a computational model of the human stomatognathic system by means of dynamic analysis software (LMS DADS). Only the masseter muscle, the temporal muscle and the medial pterygoid muscle were taken into account - the lateral pterygoid muscle was left out. RESULTS: The simulations yielded the basic kinematic and dynamic parameters characterizing the muscles. CONCLUSIONS: Summing up, weaker occlusion forces are needed to bite off today's foodstuffs than the forces which the mastication muscles are capable of generating. Determined in the article the general equations will enable identification of the muscular forces acting on the mandible during biting off, performing basic strength calculations, and will also give an answer to which of the products the patient after a surgical procedure will be able to consume. PMID- 27405537 TI - The thumb carpometacarpal joint: curvature morphology of the articulating surfaces, mathematical description and mechanical functioning. AB - PURPOSE: The purpose is to present a mathematical model of the function of the thumb carpometacarpal joint (TCMCJ) based on measurements of human joints. In the TCMCJ both articulating surfaces are saddle-shaped. The aim was to geometrically survey the shapes of the articulating surfaces using precise replicas of 28 TCMCJs. METHODS: None of these 56 articulating surfaces did mathematically extend the differential geometrical neighbourhood around the main saddle point so that each surface could be characterised by three main parameters: the two extreme radii of curvature in the main saddle point and the angle between the saddles' asymptotics (straight lines). RESULTS: The articulating surfaces, when contacting at the respective main saddle points, are incongruent. Hence, the TCMCJ has functionally five kinematical degrees of freedom (DOF); two DOF belong to flexion/extension, two to ab-/adduction. These four DOF are controlled by the muscular apparatus. The fifth DOF, axial rotation, cannot be adjusted but stabilized by the muscular apparatus so that physiologically under compressive load axial rotation does not exceed an angle of approximately +/-3 degrees . CONCLUSIONS: The TCMCJ can be stimulated by the muscular apparatus to circumduct. The mechanisms are traced back to the curvature incongruity of the saddle surfaces. Hence we mathematically proved that none of the individual saddle surfaces can be described by a quadratic saddle surface as is often assumed in literature. We derived an algebraic formula with which the articulating surfaces in the TCMCJ can be quantitatively described. This formula can be used to shape the articulating surfaces in physiologically equivalent TCMCJ-prostheses. PMID- 27405538 TI - How many enzyme molecules are needed for discrimination oriented applications? AB - Chemical reactions establish a molecular mechanism for information processing in living organisms. Here we consider a simple enzymatic reaction model that can be used to discriminate parameters characterizing periodic reagent inflow. Numerical simulations based on the kinetic equations show that there exist a range of inflow frequencies and amplitudes in which the time evolution of the system is very sensitive to small changes in the values of these parameters. However, the kinetic equations are derived for the thermodynamic limit, whereas in a real biological medium, like a cell, the number of enzyme molecules is an integer and finite. We use stochastic simulations to estimate discriminator reliability as a function of the number of enzyme molecules involved. For systems with 10 000 molecules the functionality predicted by kinetic equations is confirmed. If the number of molecules is decreased to 100, discrimination becomes unreliable. PMID- 27405539 TI - Evaluation of egg white ovomucin-based porous scaffold as an implantable biomaterial for tissue engineering. AB - Studies have shown the technological and functional properties of ovomucin (OVN) in the food-agricultural industry. But research has yet to explore its potential as an implantable biomaterial for tissue engineering and regenerative medicine. In this study we isolated OVN from egg white by isoelectric precipitation and fabricated scaffolds with tunable porosity by utilizing its foaming property. Gelatin a known biocompatible material was introduced to stabilize the foams, wherein different ratios of OVN and gelatin had a significant effect on the degree of porosity, pore size and stability of the formed hydrogels. The porous scaffolds were crosslinked with EDC resulting in stable scaffolds with prolonged degradation. Improved cell proliferation and adhesion of rat bone marrow-derived mesenchymal stem cells were observed for OVN containing scaffolds. Although, scaffolds with 75% OVN showed decrease in cell proliferation for L929 fibroblast type of cells. Further biocompatibility assessment as implant material was determined by subcutaneous implantation in rats of selected scaffold. H&E staining showed reasonable vascularization over time and little evidence of severe fibrosis at the implant site. Persistent polarization of classically activated macrophage was not observed, potentially reducing inflammatory response, and showed increased expression of alternatively activated macrophage cells that is favorable for tissue repair. Analysis of IgE levels in rat serum after implantation indicated minimal and resolvable allergic response to the OVN implants. The results demonstrate OVN as an acceptable implant scaffold that could provide new opportunities as an alternative natural biocompatible and functional biomaterial in various biomedical applications. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2107-2117, 2017. PMID- 27405540 TI - Ultrahigh brilliance quasi-monochromatic MeV gamma-rays based on self synchronized all-optical Compton scattering. AB - Inverse Compton scattering between ultra-relativistic electrons and an intense laser field has been proposed as a major route to generate compact high brightness and high-energy gamma-rays. Attributed to the inherent synchronization mechanism, an all-optical Compton scattering gamma-ray source, using one laser to both accelerate electrons and scatter via the reflection of a plasma mirror, has been demonstrated in proof-of-principle experiments to produce a x-ray source near 100 keV. Here, by designing a cascaded laser wakefield accelerator to generate high-quality monoenergetic e-beams, which are bound to head-on collide with the intense driving laser pulse via the reflection of a 20-um-thick Ti foil, we produce tunable quasi-monochromatic MeV gamma-rays (33% full-width at half maximum) with a peak brilliance of ~3 * 10(22) photons s(-1) mm(-2) mrad(-2) 0.1% BW at 1 MeV. To the best of our knowledge, it is one order of magnitude higher than ever reported value of its kinds in MeV regime. This compact ultrahigh brilliance gamma-ray source may provide applications in nuclear resonance fluorescence, x-ray radiology and ultrafast pump-probe nondestructive inspection. PMID- 27405541 TI - Parametric instability of optical non-Hermitian systems near the exceptional point. AB - In contrast to Hermitian systems, the modes of non-Hermitian systems are generally nonorthogonal. As a result, the power of the system signal depends not only on the mode amplitudes but also on the phase shift between them. In this work, we show that it is possible to increase the mode amplitudes without increasing the power of the signal. Moreover, we demonstrate that when the system is at the exceptional point, any infinitesimally small change in the system parameters increases the mode amplitudes. As a result, the system becomes unstable with respect to such perturbation. We show such instability by using the example of two coupled waveguides in which loss prevails over gain and all modes are decaying. This phenomenon enables compensation for losses in dissipative systems and opens a wide range of applications in optics, plasmonics, and optoelectronics, in which loss is an inevitable problem and plays a crucial role. PMID- 27405542 TI - Late presentation for diagnosis of HIV infection among HIV positive patients in South Tigray Zone, Ethiopia. AB - BACKGROUND: In spite of the availability and accessibility of HIV testing opportunities and efforts, people are being late to test in the course of HIV infection. Late diagnosis leads to late anti-retroviral therapy initiation which in turn results in poor treatment outcome and prognosis of the disease. The aim of this study was to determine the prevalence and predictors of late HIV diagnosis among HIV-infected patients in South Tigray Zone, Ethiopia. METHODS: A facility based cross sectional study was conducted among HIV positive patients from February 1-30, 2014 in Southern Tigray, Ethiopia. Multistage sampling technique was employed to select the study participants. Data were collected by reviewing patient medical card and interviewing using structured questionnaire. Data were entered using Epi-Data version 3.1 and analyzed using SPSS version 20.0. Both bivariate and multivariate logistic regressions were modeled to evaluate the association of predictors with late diagnosis of HIV infection. RESULTS: Out of 789 study participants, 68.8 % of them were late for HIV diagnosis. Feeling healthy (65.7 %), fear of stigma and discrimination (32.4 %) and using traditional treatment (1.5 %) were reported as the main reasons for late HIV diagnosis. Use of Khat [AOR = 3.27, 95 % CI (1.75, 6.13)], bed ridden functional status [AOR = 2.66, 95 % CI (1.60, 4.42)], ambulatory functional status [AOR = 1.56, 95 % CI (1.03, 2.35)] and Muslim religion [AOR = 2.26, 95 % CI (1.13, 4.49)] were significantly associated with late presentation for HIV diagnosis. CONCLUSIONS: High prevalence of late HIV diagnosis was recorded in Southern Tigray Zone, Ethiopia. Public health educations and campaigns targeted at improving early diagnosis and prognosis of people living with HIV/AIDS in Southern Tigray, Northern Ethiopia should be underway. PMID- 27405543 TI - Streptomyces palmae sp. nov., isolated from oil palm (Elaeis guineensis) rhizosphere soil. AB - Actinomycete strain CMU-AB204T was isolated from oil palm rhizosphere soil collected in Chiang Mai University (Chiang Mai, Thailand). Based on morphological and chemotaxonomic characteristics, the organism was considered to belong to the genus Streptomyces. Whole cell-wall hydrolysates consisted of ll-diaminopimelic acid, glucose, ribose and galactose. The predominant menaquinones were MK-9(H4), MK-9(H6), MK-9(H2) and MK-8(H4). The fatty acid profile contained iso-C15 : 0, iso-C16 : 0 and anteiso-C15 : 0 as major components. The principal phospholipids detected were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The DNA G+C content of strain CMU-AB204T was 70.9 mol%. Based on 16S rRNA gene sequence similarity, strain CMU-AB204T was closely related to Streptomyces orinoci JCM 4546T (98.7 %), Streptomyces lilacinus NBRC 12884T (98.5 %), Streptomyces abikoensis CGMCC 4.1662T (98.5 %), Streptomyces griseocarneus JCM 4905T (98.4 %) and Streptomyces xinghaiensis JCM 16958T (98.3 %). Phylogenetic trees revealed that the new strain had a distinct taxonomic position from closely related type strains of the genus Streptomyces. Spiny to hairy spores clearly differentiated strain CMU-AB204T from the five most closely related Streptomyces species, which produced smooth spores. On the basis of evidence from this polyphasic study, it is proposed that strain CMU-AB204T represents a novel species of the genus Streptomyces, namely Streptomyces palmae sp. nov. The type strain is CMU-AB204T (=JCM 31289T=TBRC 1999T). PMID- 27405545 TI - Oxidant stress distressed. PMID- 27405544 TI - Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution. AB - Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A > G, [c.329 - 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C > T, c.755 - 1G > C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G > T, c.1452 + 1G > A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C > T, c.851_854del4, c.1078C > T, IVS11 + 1G > A, c.1364G > T, c.1399C > T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C > T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas. PMID- 27405547 TI - Redox Report E-letter RedoxRep@aol.com. PMID- 27405546 TI - 'Oxidative stress' really dead? PMID- 27405548 TI - Tyrosine phosphorylation: a signal for the activation of the phagocyte respiratory burst. AB - The respiratory burst of the phagocytic cell is a unique function which provides the cell with a series of reactive oxygen intermediates which it can use to kill ingested microorganisms. The complex signal transduction pathways responsible for regulating the respiratory burst are yet to be fully elucidated. Protein tyrosine kinases are now recognised as being critical components in the regulatory pathways controlling many cellular functions. In this report we review the evidence implicating tyrosine phosphorylation as an important signal for the activation of the phagocyte respiratory burst. PMID- 27405549 TI - The effect of oxidative stress on Saccharomyces cerevisiae. AB - Reactive oxygen species (ROS) are highly reactive and damage cellular constituents such as DNA, lipids and proteins. All aerobically growing organisms are exposed to ROS. As a result most organisms have evolved mechanisms to protect their components against ROS. This review describes the oxidant defence systems of the yeast Saccharomyces cerevisiae, which is an ideal eukaryotic model system to analyse the molecular events in response to oxidative stress. Yeast posses a similar range of anti-oxidant molecules and enzymes to those found in higher eukaryotes. Exponentially growing S. cerevisiae have at least two distinct adaptive stress responses to oxidants, one of which is responsive towards H2O2 and the other is induced by exposure to compounds that generate superoxide anion. The identification of a number of transcription factors (Yap1, Mac1, Ace1) which are important in the regulation of metal metabolism and homeostasis that are also involved in mediating resistance towards oxidants suggests a link between metal metabolism and oxidative stress. Heat-shock, nutrient starvation and entry into the stationary phase of growth also lead to increased resistance toward oxidants. The available evidence suggests that the mechanism by which these stresses result in oxidant resistance may be different from those utilised by exponentially growing cells. PMID- 27405550 TI - Ubiquinone-10 plasma concentrations in healthy European children. AB - The reduced form of ubiquinone-10 (coenzyme Q) has been shown to represent an important physiologic antioxidant principle in human blood. In order to establish a reference range for infants, we measured plasma levels of ubiquinone in 50 healthy European children aged 2 months to 15 years. A mean +/-SD) value of 0.75+/-0.27 MUg/ml plasma (0.87+/-0.31 MUM) was determined; ubiquinone concentrations were not found to be sex-dependent (0.7+/-0.24MUg/ml for girls, n=17, and 0.7+/-0.28MUg/ml for boys, n=33) but correlated negatively with age (r = -0.37, P=0.0075). This negative correlation was mainly due to relatively high levels in infants approximately 1 year old. The mean value determined does not significantly differ from the average ubiquinone plasma concentrations determined in healthy Nigerian children (0.85+/-0.40 MUg/ml, n= 18) in a previous study (Becker K, Boetticher D, Leichsenring M. Internat J Vitam Nutr Res 1995, in press). PMID- 27405551 TI - Activity of Cu2Zn2 superoxide dismutase against the human immunodeficiency virus type 1. AB - The anti-retroviral activity of Cu2Zn2 superoxide dismutase (SOD; EC 1.15.1.1) was tested in Molt-4 cells infected with the human immunodeficiency virus type 1 (HIV-1) and compared to the anti-HIV-1 activity of the reverse transcriptase inhibitors azidothymidine (AZT), dideoxycytidine (ddC), dideoxyuridine (ddU) and phosphono-formic acid, the glucosidase I inhibitors castanospermine and dihydroxymethyl dihydroxy-pyrrolidine (DMDP), the HIV protease inhibitor RO-31 7595 as well as the CD4-masking compound aurintricarboxylic acid. 300 nM of SOD sufficed to reduce the release of the viral antigen gp 120 of HIV-1NDK-infected Molt-4 cells by 50% [EC50]. Cytotoxic effects of SOD were estimated by cell counts and rates of cell growth. SOD, 3 MUM, reduced the cell growth of uninfected cells by 50% [TC50]. While copper-free apo-SOD displayed no anti-HIV activity, the [EC50] of heat-inactivated enzyme was 1 MUM, suggesting an anti retroviral effect of low molecular weight active center degradation products of SOD. The [EC50] of SOD reached 10% of AZT's anti-HIV-1NDK activity and exceeded all tested anti-retrovirals 40-3000-fold. The selectivity index (Si= [TC50]/[EC50) for SOD was 10, resembling the reverse transcriptase inhibitors dideoxycytidine and phosphonoformic acid. SOD inhibited also dose-dependently the oxidative stress induced depletion of sulfhydryls, which are crucially involved in the nuclear factor kappa B controlled HIV transcription. PMID- 27405552 TI - Hydrogen peroxide and catalase in UVA-induced lipid peroxidation in cultured fibroblasts. AB - UVA-induced lipid peroxidation in cultured human skin fibroblasts, as measured by the release in the supernatant of thiobarbituric acid-reactive substances, is found to be linear with increasing irradiation dose (up to about 250 kJ m(-2)). Concomitantly, within this dose range catalase is strongly inactivated by UVA radiation according to an exponential process (k~0.01 kJ(-1) m(2)). This suggests that catalase is not involved in modulating the peroxidation process. Inactivation of catalase by 3-amino-1,2,4-triazole can be efficiently achieved prior to irradiation. This inactivation has no consequence on the extent of peroxidation triggered by subsequent exposure to UVA radiation. It may be therefore strongly suggested that catalase is not, via H2O2 removal, a key enzyme in the cellular defence equipment towards UV A-peroxidative stress. An alternative interpretation may be formulated which supports the view that H2O2 produced upon exposure to UVA has no or very little role in triggering the lipid peroxidation process. PMID- 27405553 TI - Control of NADH ferricyanide reductase activity in the human erythrocyte by somatotrophin and insulin. AB - Reduction of external ferricyanide by the human erythrocyte is significantly stimulated by insulin and somatotrophin at concentrations above physiological levels. Basal (in absence of hormones) and hormone-stimulated activities are attenuated in the presence of glycolytic inhibitors iodoacetate and vanadate indicating the requirement of glycolytic substrates for the reduction process and for the activation of cellular metabolism in response to the hormones. Sulfhydryl reagents like N-ethylmaleimide also attenuate the basal and hormone-stimulated activities and this effect was rationalized on the basis of action at SH sites which trigger responses to hormones. Stimulation of ferricyanide reduction by insulin and somatotrophin may be also the result of Na(+)/H(+) antiport activation which may be prevented by amiloride. This suggests that Na(+)/H(+) antiport is part of the membrane transduction system for insulin and somatotrophin in the human erythrocyte. These observations are a contribution to the study of plasma membrane oxidoreductase systems involved in physiological and metabolic functions of the cell. PMID- 27405554 TI - Redox conditions specify the proteins synthesised by isolated chloroplasts and mitochondria. AB - In chloroplasts and mitochondria isolated from pea leaves, (35)S-methionine incorporation reveals that different subsets of proteins are selected for synthesis in the presence of the external redox reagents ferricyanide, ascorbate, duroquinol, dithiothreitol and dithionite, and in the presence of different electron transport inhibitors in the light (in chloroplasts) or with respiratory substrates (in mitochondria). Redox state of specific electron carriers may therefore regulate expression of specific genes in chloroplasts and mitochondria. The results are consistent with the hypothesis that chloroplast and mitochondrial genomes encode proteins whose synthesis must be regulated by electron transport in photosynthesis and respiration. PMID- 27405555 TI - Irreversible inactivation of glutathione S-transferase-pi by a low concentration of naphthoquinones. AB - pi-Class glutathione S-transferase (GST-pi) was very potently inactivated by oxidants such as H2O2, xanthine-xanthine oxidase and naphthoquinones. Thiols and glutathione analogs including dithiothreitol, reduced gluta-thione, cysteine, cysteamine, S-methyl-SG, S-hexyl-SG and S-decyl-SG protected GST-pi from the inactivation, but a substrate analog (2,4-dinitrophenol), superoxide dismutase and catalase did not, suggesting that the cysteinyl residue(s) in/nearby the glutathione binding site (G-site) may be oxidatively modified by these oxidants. Many reductants and radical scavengers including butylated hydoxytoluene, alpha tocopherol, ascorbate, uric acid, mannitol, tyrosine, tryptophan, histidine, quercitrin and bilirubin had no effect on the inactivation. GST-pi pretreated with cystamine was reactivated very efficiently by 50 mM DTT following incubation with 1,2-naphthoquinone, whereas cystamine-untreated GST-pi was not reactivated. PMID- 27405556 TI - Antioxidant activities of dihydroxylated salicylic acid derivatives. AB - The ability of hydroxylated metabolites of salicylic acid to scavenge reactive oxygen species and to inhibit arachidonic acid metabolism was investigated. The tested trihydroxybenzoic acids (THBAs) were potent scavengers of hydroxyl and superoxide anion radicals produced by Fenton reaction and xanthine/xanthine oxidase system or activated macrophages respectively. In the same tests, salicylic acid possessed moderate O2(-) and low OH'scavenging activities. Our results demonstrate that adding two hydroxyl groups to salicylic acid strongly increases the reactive oxygen species (ROS) scavenging activities. Adding two hydroxyl groups at position 4 and 5 (2,4,5-THBA) affords the most active ROS scavenging activity probably due to the ortho unsubstituted catechol moiety. In fact, we can consider that the ROS scavenging properties of salicylic acid are essentially due to its metabolic products such as 2,3- and 2,5-DHBAs, catechol and also to THBAs. PMID- 27405557 TI - pH dependence of lipid peroxidation and albumin oxidative modification: possible implications to the pH paradox. AB - The hydrogen ion concentration may have an important influence in biological free radical reactions. We studied the effect of an acidic pH on two models of free radical-mediated damage: copper-induced lipid peroxidation in plasma and copper/hydrogen peroxide-induced oxidative modification of albumin. A reduction of pH from 7.4 to 6.6 decreased diene conjugation by 32%, thiobarbituric acid reactive substances formation by 25% and fluorescence generation by 53% in plasma exposed to cupric chloride. At pH values lower than 6.6 an even greater inhibition of lipid peroxidation in plasma was obtained. Visible fluorescence development in albumin by exposure to site-specific generation of free radicals was also increasingly reduced by decreasing pH values. From pH 7.4 to 6.6 there was a 50% fluorescence generation inhibition. The observed partial protection of lipids and proteins against oxidative damage by an acidic pH alerts to the need for rigorously controlling the pH values when assaying compounds for antioxidant properties in vitro. It may also contribute to the explanation for the protective effect of an acidic pH against anoxic cell injury and for cell death that is precipitated by a rapid return to a normal pH following reperfusion (the 'pH paradox'). PMID- 27405558 TI - Aerial oxidation of a redox-active porphyrin in the presence of a spin trap. AB - Aerial oxidation of meso-tetrakis(3,5-dimethoxy-4-hydroxyphenyl)- porphyrin 3, in the presence of the water-soluble spin trap (4-pyridyl-1-oxide)-N-t-butylnitrone (POBN), gives the porphyrin radical 4, in which spin density is localized on a phenoxyl meso-substituent. Evidence is presented to show that the spin trap inhibits solution aggregation and spin exchange of 4, but does not, as originally expected, form spin adducts with reduced-oxygen species. PMID- 27405559 TI - Synthesis and properties of DNA purine dehydrodimers: 8-8-bideoxyribonucleosides and 8-8-bideoxyribonucleotides. AB - Purine dimers are formed by oxidation of DNA. There is evidence that these dimers are not repaired by cells from the human disease xeroderma pigmentosum. It has been suggested that unrepaired purine dimers are involved in the etiogenesis of internal cancers and neural degeneration that are observed in this disease. In order to study the properties and biological consequences of such moieties, these compounds were synthesized: 8-8-(2'-deoxyadenosyl)-2'-deoxyadenosine; 8-8-(2' deoxyadenosyl)-2'-deoxyadenosine-5'-monophosphate; 8-8-(2'-deoxyadenosyl)-2' deoxyguanosine; 8-8-(2'-deoxyadenosyl)-2'-deoxyguanosine-5'-monophosphate; 8-8 (2'-deoxyguanosyl)-2'-deoxyguanosine; 8-8-(2'-deoxyguanosyl)-2'-deoxyguanosine-5' monophosphate; 8-8-(2'-deoxyguanosyl)-2'-deoxyadenosine, and 8-8-(2' deoxyguanosyl)-2'-deoxyadenosine-5'-monophosphate. Following purification, they were characterized by mass spectrometry and nuclear magnetic resonance studies. Ultraviolet, fluorescence, and circular dichroic spectra of these products were established. The behavior of these photoproducts in various chromatographic systems was elucidated. Syntheses of purine dimers and descriptions of their properties can aid the studies of their possible formation in, and excision from, oxidized DNA. PMID- 27405560 TI - The mechanism of apoptosis, cell membrane lipid peroxidation and a novel in vivo function for antioxidant vitamin E (alpha-tocopherol). AB - A critical novel function for the antioxidant vitamin E (alpha-tocopherol) may be its involvement in the control of apoptosis in which it acts as a 'gate keeper' in the regulation of membrane lipid peroxidation. The biochemical and biophysical antioxidant properties of the molecule are discussed together with recent evidence for its involvement in a possible model of the apoptotic mechanism. The original observation that led to the discovery of vitamin E (foetal resorption in pregnant rats fed on tocopherol-deficient diets) is considered as an unrecognised example of apoptosis. PMID- 27405562 TI - Incidence of persistent renal dysfunction after contrast enhanced coronary CT angiography in patients with suspected coronary artery disease. AB - Contrast-induced nephropathy (CIN) is a potentially serious complication of contrast agents used in computed tomography angiography (CTA). The aim of this study was to evaluate whether persistent renal dysfunction occurs in patients undergoing coronary CTA for suspected stable coronary artery disease (CAD). From a cohort of 957 patients undergone coronary CTA, we identified 402 patients with plasma creatinine levels collected before and within 6 months after CTA. According to the definition of CIN, patients with a >=25 % increase in plasma creatinine after CTA were evaluated. The post-CTA measurements in 402 patients (195 men, age 62.9 +/- 9.3 years) were performed at a median of 99 days after CTA. On average, there was no change in plasma creatinine level between the pre- and post-CTA measurements (75.8 +/- 16.0 and 75.7 +/- 16.4 umol/L, respectively; P = 0.63) but both increases and decreases were commonly detected. Fourteen (3.5 %) patients had a >=25 % increase in plasma creatinine levels after CTA. A more detailed evaluation of these patients revealed that in 4 patients the increase was explained by other morbidities, whereas in 9 patients the creatinine level returned to the previous levels at later follow-up (median time to normalization: 311 days). Only in 1 (0.2 %) remaining patient, there was a persistent increase in plasma creatinine level, possibly related to the iodine contrast agent exposure. Alterations in plasma creatinine concentration occur frequently. Persistent renal dysfunction attributable to iodine contrast agent exposure is rare in patients referred to coronary CTA for suspected CAD. PMID- 27405563 TI - Regeneration of dermal patterns from the remaining pigments after surgery in Eublepharis macularius (a case report). AB - BACKGROUND: Dermal injury of the Eublepharis macularius (leopard gecko) often results in a loss of the spotted patterns. The scar is usually well recovered, but the spots and the tubercles may be lost depending on the size and part of the lesion. This report presents a surgical attempting, in which the pigments in the edge of the remaining skin flap are partially preserved to maximally restore the natural pigmentation patterns during the course of dermal regeneration. CASE PRESENTATION: A four-year-old female lizard E. macularius was evaluated due to a subcutaneous tumor in the occipito-pterional portion behind its right eye. A solid tumor beneath the skin was surgically enucleated under general anesthesia. Then, the ulcerated skin was dissected away together with the tumor. The necrotic edge of the remaining skin flap was carefully trimmed to leave as much of the pigmented portions as possible on the outskirt of the skin flap. The scar was covered with the remaining skin flap, and the uncovered lesion was protected with Vaseline containing gentamicin. The lesion was rapidly covered with regenerated dermis within a week, and the epidermis with round and well-oriented pigmented spots were almost completely restored in four months. CONCLUSION: The surgical suture of the skin flap after removal of the ulcerated margins resulted in the scar-free regeneration of the scales and the pigmented spots. And the pigmented spots of the remaining skin close to the lesion site might be a source of the regenerated spots. PMID- 27405565 TI - [Thoracic endometriosis with aspecific manifestation]. AB - BACKGROUND: Endometriosis is a common disease, especially in subfertile women. The most common location is in the pelvis, but extragenital locations are also possible. This far less common condition has been described in almost all tissues in the body. Symptoms occurring cyclically are characteristic of endometriosis. CASE DESCRIPTION: A 37-year-old woman was discovered by chance to have ascites and pleural effusion. She had no symptoms of this. Thoracoscopy showed an image consistent with thoracic endometriosis. After initial drug therapy was unsuccessful, surgical intervention was performed. CONCLUSION: Thoracic endometriosis is a rare disease, in which the cyclical nature of the symptoms often leads to correct diagnosis. Drug therapy is the preferred treatment for patients. PMID- 27405566 TI - [Conflicts between healthcare professionals and families of a multi-ethnic patient population in the intensive care unit]. AB - OBJECTIVE: To investigate which factors contribute to conflicts between healthcare professionals and family members from ethnic minority groups during medically critical situations in hospital. DESIGN: Descriptive, ethnographic research. METHOD: Ethnographic fieldwork was carried out in one intensive care unit (ICU) of a multi-ethnic urban hospital in Belgium in the period January-June 2014. Data were collected by means of negotiated interactive observation, in depth interviews with healthcare professionals and examining the patients' medical files. Data were analysed using grounded theory procedures. RESULTS: Conflicts were primarily related to the participants' different views on 'good care'. Healthcare providers' (HCPs') views on good care were primarily grounded on a biomedical care model, whereas families' views on good care were mainly inspired by a holistic care approach. According to HCPs, giving good care included fighting the disease efficiently with great scientific competence, but family members considered this rather as attending to the patient and giving bedside care, amongst other things. The HCPs' biomedical vision on good care was strengthened by the strict application of ward regulations, characterizing the ICU setting. The families' holistic views on good care were strengthened by specific ethno-familial characteristics, including their ethno-cultural background. However, ethno-cultural differences only contributed to conflict if the policy context on the ICU could provoke this conflict. CONCLUSION: Conflicts cannot be exclusively linked to ethno-cultural differences. Structural, functional characteristics of the ICU contribute substantially to conflict development. Effective conflict prevention should, therefore, not only focus on ethno-cultural differences but should also focus sufficiently on the structural context and ward policy. PMID- 27405564 TI - Aberrant DNA methylation of acute myeloid leukemia and colorectal cancer in a Chinese pedigree with a MLL3 germline mutation. AB - Unlike genetic aberrations, epigenetic alterations do not modify the deoxyribonucleic acid (DNA) coding sequence and can be reversed pharmacologically. Identifying a particular epigenetic alteration such as abnormal DNA methylation may provide better understanding of cancers and improve current therapy. In a Chinese pedigree with colorectal carcinoma and acute myeloid leukemia, we examined the genome-wide DNA methylation level of cases and explored the role of methylation in pathogenesis and progression. DNA methylation status in the four cases, which all harbor a MLL3 germline mutation, differed from that of the normal control, and hypermethylation was more prevalent. Also, more CpG sites were hypermethylated in the acute-phase AML patient than in the AML patient in remission. Fifty-nine hyper- or hypomethylated genes were identified as common to all four cases. Genome-wide DNA methylation analysis demonstrated that differentially methylated sites among acute myeloid leukemia and colorectal carcinoma cases and the control were in both promoters (CpG island) and gene body regions (shelf/shore areas). Hypermethylation was more prevalent in cancer cases. The study supports the suggestion that the level of DNA methylation changes in AML progression. PMID- 27405567 TI - [Can I still get pregnant? Options for fertility preservation in young women diagnosed with cancer]. AB - - In 2015 around 2300 women under the age of 40 years were diagnosed with cancer in the Netherlands.- Cancer treatment can have a negative effect on fertility.- Due to improving survival rates, discussing this effect and the options for fertility preservation has become an important part of counselling these patients.- Cryopreservation of oocytes and embryos is standard procedure in fertility preservation in the Netherlands.- Cryopreservation of ovarian tissue is a new, rapidly-developing technique. Recently, the first child following autotransplantation of thawed ovarian tissue was born in the Netherlands.- If gonadotoxic treatment has to be given, it is important to talk well in advance with the patient about fertility preservation. PMID- 27405568 TI - [We are living longer, but are these additional years spent in good health?]. AB - Life expectancy in western countries has increased continuously over recent years. The issue at stake is if this rise includes healthy years. The answer depends on the health indicator used, e.g., perceived health, disability, or cognitive impairment. A study by Jagger et al. (2016) provides evidence for an increase in life expectancy without cognitive impairment and an absolute compression of cognitive impairment between 1991 and 2011. Information on life expectancy without cognitive impairment is not yet available for the Netherlands. Similar to England, Dutch trends in life expectancy in excellent or good self perceived health and in life expectancy without severe disability are favourable, although less pronouncedly so. Dutch and English data suggest that the additional years lived by the population are at least partly spent in good health. PMID- 27405569 TI - [Docetaxel for metastatic prostate cancer: early is better]. AB - Androgen deprivation therapy (ADT) has been used to treat patients with metastatic prostate cancer for many years. Docetaxel chemotherapy administered to patients with metastatic castrate-resistant prostate cancer has been standard since 2004 with a modest survival benefit. Recent data from two randomised studies (CHAARTED and STAMPEDE) demonstrate that combining ADT with docetaxel in men with hormone-naive metastatic prostate cancer resulted in an impressive overall survival benefit of more than a year as compared with ADT alone. In a meta-analysis, the consistency of these data was confirmed. On the basis of these data, addition of six 3-weekly courses of docetaxel to ADT should be considered as standard treatment in chemo-fit patients with hormone-naive metastatic prostate cancer. PMID- 27405570 TI - [A toddler with a swelling of his penis]. AB - A 4-year-old boy presented with a subcutaneous, yellowish swelling of 0.8 by 1.5 cm on his penis. We made the diagnosis of a smegma retention cyst. This cyst is the result of a physiologic phenomenon that originates from the separation of the foreskin. PMID- 27405571 TI - [From annual check-up to annual appraisal: personalised diabetes care]. AB - Diabetes care is shifting from disease management to personalised care. Internationally, diabetes care providers are advised to integrate the patient's preferences, wishes and possibilities into diabetes care in order to improve its efficiency. The Dutch Diabetes Federation has developed a specifically patient centred conversation model that can be systematically applied. At an annual appraisal, the physician and the patient make decisions on the treatment goals to set, and on the treatment and professional support needed to achieve these goals. In this way person-centred and efficient care may become reality. The first results of a pilot study are promising. Currently the applicability and added value of the model are being tested on a large scale. The model is more broadly applicable, which means this could be a new perspective for everyone with a chronic disease. PMID- 27405572 TI - [Heart failure in nursing home residents]. AB - OBJECTIVE: To determine the prevalence of heart failure (HF) in nursing home residents and to gain insight into the clinical characteristics of residents with heart failure. DESIGN: Multi-centre, observational, cross-sectional study. METHOD: 501 nursing home residents aged 65 years and over, in a department for chronic somatic diseases or a psychogeriatric department, participated in this study. The diagnosis of HF and the related characteristics were based on data collected from clinical examinations for heart failure (including history, physical examination, ECG, cardiac markers and echocardiography), patient records and questionnaires. A panel of two cardiologists and an internist-geriatrician made the final diagnosis of HF. RESULTS: The prevalence of HF in nursing home residents was 33%. Dyspnoea, oedema and a history of cardiac disease were more common in residents with heart failure. Diabetes mellitus and chronic obstructive pulmonary disease also appeared to be more prevalent in this group. In 54% of the residents with HF, the diagnosis had not previously been made. Diagnosis of HF was not confirmed by the expert panel in 31% of residents with a history of HF. CONCLUSION: Heart failure does indeed appear to be very prevalent in nursing home residents. Heart failure had not been previously diagnosed in many cases but also a previous diagnosis of heart failure could be disproved in many participants. It is therefore important that the diagnostic process for heart failure in nursing home residents be improved. PMID- 27405573 TI - [A man with an image from the past]. AB - In the past intrathecal injection of ethiodized oil was used as a radio-opaque contrast agent. Nowadays the intrathecal use of ethiodized oil is very limited, however because of its inert properties it remains visible on radiological investigations even many decades after injection. Therefore, knowledge and recognition of this radiological feature is important since this prevents unnecessary further investigations. PMID- 27405575 TI - [The return of the hepatitis delta virus]. AB - - There are several regions worldwide with a high prevalence of infection with the hepatitis delta virus (HDV) in hepatitis B virus (HBV) carriers.- Chronic HDV infection is occurring with increasing frequency due to increased immigration.- HDV transmission can take place through the same routes as HBV by simultaneous infection with both viruses (co-infection) or infection of an HBV carrier with HDV (superinfection).- Delta hepatitis is considered as the most severe form of viral hepatitis with a high risk of progression to cirrhosis and hepatocellular carcinoma.- Chronic delta hepatitis is exclusively observed in patients who are HBV carriers.- Pegylated interferon is currently the only registered therapy for patients with delta hepatitis, but leads to a persistent virological response in only a minority of them, and rarely leads to a complete cure.- New antivirals, such as viral entry blockers, prenylation inhibitors and anti-sense oligonucleotides are promising and currently being investigated in phase 2 trials. PMID- 27405574 TI - [Changes between pre-crisis and crisis period in socioeconomic inequalities in health and stimulant use in Netherlands]. AB - OBJECTIVE: International research suggests an impact of economic crises on population health, with different effects among different socioeconomic groups. Since the end of 2008 the Netherlands experienced a period of economic crisis. Our study explores how inequalities in perceived general and mental health, and alcohol and tobacco use changed after the recession started. DESIGN: Cross sectional study using routinely collected data from surveys of the Dutch population. METHOD: We used data from the Dutch Health Interview Surveys: 2006 2008 (pre-crisis period) and 2009-2013 (crisis period). Respondents aged 25-64 were divided into socioeconomic groups based on labour status, income level and income change. Inequalities in health and stimulant use among these socioeconomic groups were described by period and changes between the pre-crisis and crisis period were investigated using logistic regression models. RESULTS: Most inequalities did not change, with some exceptions. For perceived general health, inequalities between employed persons and persons not in the labour force were larger in the crisis-period (unfavourable trends for those not in the labour force). For smoking, inequalities between unemployed and employed persons were larger in the crisis period (decreasing smoking rates only for those employed), as did inequalities between persons with low and high income levels (decreasing smoking rates for those with higher income levels). Excessive drinking decreased among employed persons and persons with a decrease in income, while it remained stable among persons not in the labour force and among persons with an increase in income. CONCLUSION: The widening of some socioeconomic inequalities in health and stimulant use might suggest an enhanced vulnerability of lower socioeconomic groups to the post-2008 crisis. PMID- 27405576 TI - [Intermittent swelling of the eyelid]. AB - BACKGROUND: Mucoceles are benign mucous-containing cysts that can occur in the sinuses. They arise as a result of an obstruction of the sinus ostium. There is often a delay in diagnosis because symptoms are so variable. CASE DESCRIPTION: A 52-year-old woman had intermittent swelling of the eyelid. A CT scan of the sinuses showed a mucocele in the frontal sinus with breakthrough to the left orbit. Treatment consisted of marsupialisation by means of functional endoscopic sinus surgery with septum correction. CONCLUSION: Breakthrough of a mucocele to the orbit should be considered in the differential diagnosis in patients with an intermittent swelling of the eyelid. PMID- 27405578 TI - Future perspective of CAS in orthopaedics. PMID- 27405577 TI - Complications of medial patellofemoral ligament reconstruction using two transverse patellar tunnels. AB - PURPOSE: The aim of this study was to report the complication rate after a medial patellofemoral ligament (MPFL) reconstruction using transverse patellar tunnels in a retrospective case series performed in a single institution. METHODS: Case series of 179 patients (192 knees) that had an MPFL reconstruction, with or without additional bony realignment procedures, between January 2009 and March 2015. Data were obtained from available patient charts. RESULTS: Thirty-nine complications (20.3 %) were registered. Twenty-seven of these (14.7 %) were minor. Seven patients (3.6 %) sustained a patellar fracture without adequate trauma. Male gender was a risk factor for patellar fracture (p < 0.001). Sixteen (8.1 %) reported recurrence of instability, of whom 10 (5.1 %) were defined as objective instability (reported dislocation and positive apprehension test). CONCLUSION: This is largest patient series to date in which the complications after a two tunnel MPFL reconstruction are described. The use of transverse patellar tunnels increases the risk of sustaining a patellar fracture. LEVEL OF EVIDENCE: IV. PMID- 27405579 TI - Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI. AB - Amyloid PET is useful for early and/or differential diagnosis of Alzheimer's disease (AD). Quantification of amyloid deposition using PET has been employed to improve diagnosis and to monitor AD therapy, particularly in research. Although MRI is often used for segmentation of gray matter and for spatial normalization into standard Montreal Neurological Institute (MNI) space where region-of interest (ROI) template is defined, 3D MRI is not always available in clinical practice. The purpose of this study was to examine the feasibility of PET-only amyloid quantification with an adaptive template and a pre-defined standard ROI template that has been empirically generated from typical cases. A total of 68 subjects who underwent brain (11)C-PiB PET were examined. The (11)C-PiB images were non-linearly spatially normalized to the standard MNI T1 atlas using the same transformation parameters of MRI-based normalization. The automatic anatomical-labeling-ROI (AAL-ROI) template was applied to the PET images. All voxel values were normalized by the mean value of cerebellar cortex to generate the SUVR-scaled images. Eleven typical positive images and eight typical negative images were normalized and averaged, respectively, and were used as the positive and negative template. Positive and negative masks which consist of voxels with SUVR ?1.7 were extracted from both templates. Empirical PiB-prone ROI (EPP-ROI) was generated by subtracting the negative mask from the positive mask. The (11)C PiB image of each subject was non-rigidly normalized to the positive and negative template, respectively, and the one with higher cross-correlation was adopted. The EPP-ROI was then inversely transformed to individual PET images. We evaluated differences of SUVR between standard MRI-based method and PET-only method. We additionally evaluated whether the PET-only method would correctly categorize (11)C-PiB scans as positive or negative. Significant correlation was observed between the SUVRs obtained with AAL-ROI and those with EPP-ROI when MRI-based normalization was used, the latter providing higher SUVR. When EPP-ROI was used, MRI-based method and PET-only method provided almost identical SUVR. All (11)C PiB scans were correctly categorized into positive and negative using a cutoff value of 1.7 as compared to visual interpretation. The (11)C-PiB SUVR were 2.30 +/- 0.24 and 1.25 +/- 0.11 for the positive and negative images. PET-only amyloid quantification method with adaptive templates and EPP-ROI can provide accurate, robust and simple amyloid quantification without MRI. PMID- 27405581 TI - Community-based, nurse-led post-exposure prophylaxis: results and implications. AB - HIV medications can be used as post-exposure prophylaxis to efficaciously prevent an HIV-negative person who has come into contact with HIV from becoming HIV positive. Traditionally, these medications have been available in emergency departments, which have constituted a barrier for the members of many minority groups who are greatly affected by HIV transmission (i.e. gay, bisexual and other men who have sex with men, and persons who use injection drugs). From 5 September 2013 through 4 September 2015, we sought to increase the use of HIV post-exposure prophylaxis by having registered nurses provide these medications, when indicated, in community clinics in Ottawa, Canada. We undertook a chart review of patients who accessed services for HIV post-exposure prophylaxis in this period. Over the two years of data collection, 112 persons requested HIV post-exposure prophylaxis and 64% (n = 72) initiated these medications. Most (93%, or n = 67, of the 72 initiations) were among men, with 88% (n = 59) of these men reporting same sex sexual partners. Among these 58 men, 31% (n = 18) had sexual contact with other men known to be HIV-positive. Among women (n = 8), five initiated post exposure prophylaxis: three after needle-sharing contact or sexual contact with a male partner who reportedly shared needles, and two after unprotected vaginal sex with a male partner known to be HIV-positive. Overall, no one was diagnosed with HIV at the four-month HIV testing follow-up, although six persons were diagnosed with HIV from the baseline HIV testing, and an additional four were diagnosed with HIV during routine HIV testing one year after completing post-exposure prophylaxis. In total, nine persons in our sample were thus diagnosed with HIV during the study period, which accounted for 9.4% (n = 10 of 106) of all reported HIV diagnoses in Ottawa during this time. We conclude that nurse-initiated HIV post-exposure prophylaxis can be an effective way to provide HIV prevention services to persons who are at high-risk for HIV. PMID- 27405580 TI - Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice. AB - Photoreceptor degeneration due to retinitis pigmentosa (RP) is a primary cause of inherited retinal blindness. Photoreceptor cell-replacement may hold the potential for repair in a completely degenerate retina by reinstating light sensitive cells to form connections that relay information to downstream retinal layers. This study assessed the therapeutic potential of photoreceptor progenitors derived from human embryonic and induced pluripotent stem cells (ESCs and iPSCs) using a protocol that is suitable for future clinical trials. ESCs and iPSCs were cultured in four specific stages under defined conditions, resulting in generation of a near-homogeneous population of photoreceptor-like progenitors. Following transplantation into mice with end-stage retinal degeneration, these cells differentiated into photoreceptors and formed a cell layer connected with host retinal neurons. Visual function was partially restored in treated animals, as evidenced by two visual behavioral tests. Furthermore, the magnitude of functional improvement was positively correlated with the number of engrafted cells. Similar efficacy was observed using either ESCs or iPSCs as source material. These data validate the potential of human pluripotent stem cells for photoreceptor replacement therapies aimed at photoreceptor regeneration in retinal disease. PMID- 27405582 TI - Outbreak or illusion: consequences of 'improved' diagnostics for gonorrhoea. AB - The sexual health service in Oxford introduced gonorrhoea nucleic amplification acid testing using the BD Viper XTRTM System. For practical reasons, a confirmatory nucleic amplification acid testing using a different platform was not used initially. Following the introduction of nucleic amplification acid testing, the rates of gonorrhoea increased threefold. Concerns were raised that this increase represented an outbreak. A retrospective review of cases over six months suggested that there may have been a number of false-positive results. A prospective study was then undertaken over six months, where all gonorrhoea positive samples were sent for confirmatory testing. This evaluation of all gonorrhoea cases in an English county found that the overall presumptive false positive rates for gonorrhoea nucleic amplification acid testing using BD Viper XTRTM in our population are significant at 27% of female samples, 13.2% of heterosexual male samples, 3.5% of anogenital multiple site men who have sex with men samples and 62.8% of pharyngeal only men who have sex with men samples. The data demonstrate the need for confirmatory testing using a second nucleic acid target, as per BASHH/Public Health England guidelines, especially in low prevalence settings and extragenital sites, due to cross-reactivity with commensal Neisseria species and low positive predictive values. PMID- 27405583 TI - Combination of the non-invasive tests for the diagnosis of endometriosis. AB - BACKGROUND: About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice to accurately diagnose endometriosis. This review assessed the diagnostic accuracy of combinations of different non-invasive testing modalities for endometriosis and provided a summary of all the reviews in the non-invasive tests for endometriosis series. OBJECTIVES: To estimate the diagnostic accuracy of any combination of non-invasive tests for the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep infiltrating) compared to surgical diagnosis as a reference standard. The combined tests were evaluated as replacement tests for diagnostic surgery and triage tests to assist decision making to undertake diagnostic surgery for endometriosis. SEARCH METHODS: We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed. SELECTION CRITERIA: We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of women of reproductive age suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of a combination of several testing modalities with the findings of surgical visualisation of endometriotic lesions. DATA COLLECTION AND ANALYSIS: Three review authors independently collected and performed a quality assessment of the data from each study by using the QUADAS-2 tool. For each test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. The bivariate model was planned to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95 and above, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test). MAIN RESULTS: Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests.Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off >=25 U/ml) or CA 19.9 (cut-off >=12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off >=12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off >=20 U/ml or cut-off >=25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off >=35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal examination and TVUS reached the threshold for a SpIN test for obliterated pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI 0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95), specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis (sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)).All the tests were evaluated in individual studies and displayed wide CIs. Due to the heterogeneity and high risk of bias of the included studies, the clinical utility of the studied combination diagnostic tests for endometriosis remains unclear. AUTHORS' CONCLUSIONS: None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting. PMID- 27405584 TI - Risk stratification of prostate cancer utilizing apparent diffusion coefficient value and lesion volume on multiparametric MRI. AB - PURPOSE: To evaluate the performance of apparent diffusion coefficient (ADC) and lesion volume in potentially risk-stratifying patients with prostate cancer (PCa). MATERIALS AND METHODS: Men with elevated prostate-specific antigen or abnormal digital rectal exam underwent a 3T multiparametric magnetic resonance imaging (mpMRI) with endorectal coil. ADC maps were calculated using b values of 0, 500, 1000, and 1500; additional images were obtained with b value of 2000. We prospectively enrolled 312 men with lesions suspicious for cancer (suspicion score 2-5) on mpMRI. MRI/ultrasound fusion-guided prostate biopsies were performed. Mean ADC of suspicious lesions were correlated against lesion volume, Gleason and D'Amico risk. RESULTS: The cancer detection rate of fusion biopsy per lesion was 45.6% (206/452). Cancerous lesions were larger (median volume: 0.40 vs. 0.30 cm3 ; P = 0.016). The median ADC (*10-6 mm2 /sec) for lesions negative and positive for PCa were 984.5 and 666.5, respectively (P < 0.0001). The AUC of ADC in predicting PCa was 0.79. Larger lesions were associated with higher risk PCa (Gleason and D'Amico) and lower ADC (all P < 0.0001). CONCLUSION: The mean ADC of suspicious lesions on mpMRI was inversely correlated, while lesion volume had a direct correlation with PCa detection. Future follow-up studies are needed to assess longitudinal cancer risks of suspicious mpMRI lesions. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:610-616. PMID- 27405585 TI - Characterization of a cold-adapted esterase and mutants from a psychotolerant Pseudomonas sp. strain. AB - A cold-adapted esterase-producing strain named T1-39 was isolated from Glacier No. 1, Tianshan, People's Republic of China and identified as Pseudomonas sp. from 16S rRNA sequence analysis. The esterase (EstT1-39) secreted by this strain preferentially hydrolyzed esters of glycerol with short- and medium-chain fatty acids. Mutants of T1-39 were generated by the atmospheric and room temperature plasma method and screened for enhanced esterase activity. Among all the mutants, strain TB11 had 4.45-fold higher esterase productivity than T1-39, with high genetic stability over 10 generations of continuous cultivation. Maximum activity of EstT1-39 and EstTB11 was observed at 30 C, pH 9.0 and 25 C, pH 8.5, respectively. EstTB11 was thermally more stable (50 C for 1 H) and active over a broader pH range than EstT1-39. EstTB11 also retained 38% of its maximal activity at 0 C and was found to be able to hydrolyze milk fats into short- and medium chain fatty acids at 4 C. The characteristics of EstT1-39 made it a cold-adapted enzyme and the EstTB11 from the mutant, with its higher activity at lower temperatures, may be suitable for the production of aromas and flavors in the dairy industry. PMID- 27405586 TI - Disgust, Gender, and Social Change : Testing Alternative Explanations for the Decline of Cousin Marriage in Karo Society. AB - Among the Karo of Indonesia, the frequency of matrilateral cross-cousin (impal) marriage has declined in recent decades. We conducted a vignette experiment to assess the contributions of a handful of factors in shaping this pattern. Surprisingly, we found that cosocialization of a hypothetical woman with her impal led to increased judgments of marriage likelihood and decreased feelings of disgust in male and female respondents (n = 154). We also found that females, more than males, judged impal marriage more likely when there were practical advantages. Finally, we found that younger men expressed more disgust in response to impal marriages than did older men, while women displayed an opposite but weaker reaction. This suggests the existence of gender-specific changes in attitudes toward the practice, indicating that a full understanding may require the application of sexual conflict theory. Our study illustrates the potential utility-and limitations-of vignette experiments for studying social change. PMID- 27405587 TI - A hybrid effectiveness-implementation cluster randomized trial of group CBT for anxiety in urban schools: rationale, design, and methods. AB - BACKGROUND: Schools present a context with great potential for the implementation of psychosocial evidence-based practices. Cognitive behavioral therapy (CBT) is an evidence-based practice that has been found to be very effective in treating anxiety in various community settings, including schools. Friends for Life (FRIENDS) is an efficacious group CBT protocol for anxiety. Unfortunately, evidence-based practices for anxiety are seldom employed in under-resourced urban schools, because many treatment protocols are not a good fit for the urban school context or the population, existing behavioral health staff do not receive adequate training or support to allow them to implement the treatment with fidelity, or school districts do not have the resources to contract with external consultants. In our prior work, we adapted FRIENDS to create a more culturally sensitive, focused, and feasible CBT protocol for anxiety disorders (CBT for Anxiety Treatment in Schools (CATS)). METHODS/DESIGN: The aim of this 5-year study is to evaluate both the effectiveness of CATS for urban public schools compared to the original FRIENDS as well as compare the implementation strategies (train-the-trainer vs. train-the-trainer + ongoing consultation) by conducting a three-arm, parallel group, type 2 hybrid effectiveness-implementation trial in 18 K-8 urban public schools. We will also assess the cost-effectiveness and the mediators and moderators of fidelity. Ninety therapists, 18 agency supervisors, and 360 children will participate. The interactive systems framework for dissemination and implementation guides the training and support procedures for therapists and supervisors. DISCUSSION: This study has the potential to demonstrate that agency therapists and supervisors who have had little to no prior exposure to evidence-based practices (EBPs) can implement an anxiety disorder EBP with fidelity. Comparisons of the implementation strategies would provide large urban mental health systems with data to make decisions about the adoption of EBPs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02651402. PMID- 27405589 TI - Robot-assisted laparoscopic excision of organ of Zuckerkandl. PMID- 27405588 TI - Combination of a third generation bisphosphonate and replication-competent adenoviruses augments the cytotoxicity on mesothelioma. AB - BACKGROUND: Approximately 80 % of mesothelioma specimens have the wild-type p53 gene, whereas they contain homozygous deletions in the INK4A/ARF locus that encodes p14 (ARF) and the 16 (INK4A) genes. Consequently, the majority of mesothelioma is defective of the p53 pathways. We examined whether zoledronic acid (ZOL), a third generation bisphosphonate, and adenoviruses with a deletion of the E1B-55kD gene (Ad-delE1B55), which augments p53 levels in the infected tumors, could produce combinatory anti-tumor effects on human mesothelioma cells bearing the wild-type p53 gene. METHODS: Cytotoxicity of ZOL and Ad-delE1B55 was assessed with a WST assay. Cell cycle changes were tested with flow cytometry. Expression levels of relevant molecules were examined with western blot analysis to investigate a possible mechanism of cytotoxicity. Furthermore, the expressions of Ad receptors on target cells and infectivity were estimated with flow cytometry. Viral replication was assayed with the tissue culture infection dose method. RESULTS: A combinatory use of ZOL and Ad-delE1B55 suppressed cell growth and increased sub-G1 or S-phase populations compared with a single agent, depending on cells tested. The combinatory treatment up-regulated p53 levels and subsequently enhanced the cleavage of caspase-3, 8, 9 and poly (ADP-ribose) polymerase, but expression of molecules involved in autophagy pathways were inconsistent. ZOL-treated cells also increased Ad infectivity with a dose dependent manner and augmented Ad replication although the expression levels of integrin molecules, one of the Ad receptors, were down-regulated. CONCLUSIONS: These findings indicated that ZOL and Ad-delE1B55 achieved combinatory anti-tumor effects through augmented apoptotic pathways or increased viral replication. PMID- 27405591 TI - Three-Dimensional Field Optimization Method: Clinical Validation of a Novel Color Doppler Method for Quantifying Mitral Regurgitation. AB - BACKGROUND: Assessment of mitral regurgitation (MR) severity by echocardiography is important for clinical decision making, but MR severity can be challenging to quantitate accurately and reproducibly. The accuracy of effective regurgitant orifice area (EROA) and regurgitant volume (RVol) calculated using two dimensional (2D) proximal isovelocity surface area is limited by the geometric assumptions of proximal isovelocity surface area shape, and both variables demonstrate interobserver variability. The aim of this study was to compare a novel automated three-dimensional (3D) echocardiographic method for calculating MR regurgitant flow using standard 2D techniques. METHODS: A sheep model of ischemic MR and patients with MR were prospectively examined. Patients with a range of severity of MR were examined. EROA and RVol were calculated from 3D color Doppler acquisitions using a novel computer-automated algorithm based on the field optimization method to measure EROA and RVol. For an independent comparison group, the 3D field optimization method was compared with 2D methods for grading MR in an experimental ovine model of MR. RESULTS: Fifteen 3D data sets from nine sheep (open-chest transthoracic echocardiographic data sets) and 33 transesophageal data sets from patients with MR were prospectively examined. For sheep data sets, mean 2D EROA was 0.16 +/- 0.05 cm2, and mean 2D RVol was 21.84 +/- 8.03 mL. Mean 3D EROA was 0.09 +/- 0.04 cm2, and mean 3D RVol was 14.40 +/- 5.79 cm3. There was good correlation between 2D and 3D EROA (R = 0.70) and RVol (R = 0.80). For patient data sets, mean 2D EROA was 0.35 +/- 0.35 cm2, and mean 2D RVol was 58.9 +/- 52.9 mL. Mean 3D EROA was 0.34 +/- 0.29 cm2, and mean 3D RVol was 54.6 +/- 36.5 mL. There was excellent correlation between 2D and 3D EROA (R = 0.94) and RVol (R = 0.84). Bland-Altman analysis revealed greater interobserver variability for 2D RVol measurements compared with 3D RVol using the 3D field optimization method measurements, but variability was statistically significant only for RVol. CONCLUSIONS: Direct automated measurement of proximal isovelocity surface area region for EROA calculation using real-time 3D color Doppler echocardiography is feasible, with a high correlation to current 2D EROA methods but less variability. This novel automated method provides an accurate and highly reproducible method for calculating EROA. PMID- 27405592 TI - Is Doppler Echocardiographic Quantitation of Aortic Valve Stenosis a Settled Science? PMID- 27405594 TI - Cancer and Mortality in Solid-Organ Transplantation: Preventable or Inevitable? PMID- 27405593 TI - Pediatric Echocardiography by Work Relative Value Units: Is Study Complexity Adequately Captured? AB - BACKGROUND: Present resource-based relative value unit (RVU) assignment for echocardiography is based on Current Procedural Terminology (CPT) codes, which do not incorporate complexity of diagnosis, time spent for image acquisition, or interpretation of echocardiograms. The objective of this study was to determine whether CPT-based RVU assignment accurately reflects physician effort in performing and interpreting pediatric echocardiographic examinations. METHODS: Cardiac complexity category (CCC) and physician time for study interpretation of 123 echocardiograms (June to September 2013) were prospectively assigned. Categories included (1) focused effusion/function evaluation, (2) normal anatomy/focused preterm infant studies, (3) acquired heart disease, (4) congenital heart disease excluding single ventricles, (5) single ventricles including heterotaxy syndrome, and (6) hearts on mechanical support. Subsequently, a random sample of echocardiograms (March to August 2013) were retrospectively analyzed, and each study was assigned a CCC and an extrapolated median interpretation time (MIT) on the basis of prospective data collection. Assigned work RVUs based on CPT codes were recorded. Comparisons were made between CCC and time for study interpretation, work RVUs, number of images acquired, and total scan time. RESULTS: A total of 933 echocardiograms were analyzed: 198 (21%), 174 (19%), 98 (11%), 359 (35%), 84 (9%), and 20 (2%) studies in CCCs 1 to 6, respectively. Total scan time, MIT, number of images, and work RVUs were different among CCCs (P < .0001). However, among the more complex studies (CCCs 2-5), work RVUs were similar, while number of images obtained and MIT were different (P < .001). Correlation analysis showed no association between work RVUs and CCC, total scan, or number of images per study. Compared with older patients, work RVUs of studies in children <2 years of age were lower, while all other markers of study complexity were higher (P < .05). CONCLUSIONS: Current CPT based assignment of work RVUs does not discriminate study complexity and physician effort. The results of this study highlight the need for a refined system that accurately assesses physician effort in pediatric echocardiography. PMID- 27405595 TI - Laser ablation is more effective for spongiform than solid thyroid nodules. A 4 year retrospective follow-up study. AB - PURPOSE: Laser ablation (LA) is used as therapeutic modality for reducing the volume of large benign thyroid nodules. The aim of this retrospective study was to assess the efficacy of LA therapy in patients with benign non-functioning thyroid nodules in a 4-year follow-up and evaluate whether different compactness of nodules may influence the final shrinkage. PATIENTS AND METHODS: Fifty-six euthyroid patients (42 females; mean age 54.7 +/- 11.7 years) with benign cold thyroid solitary nodules or a dominant nodule within a multinodular goitre underwent LA between July 2009 and March 2012. Nodule volume, thyroid function test and ultrasound were monitored at baseline, and at 3, 6 and 12 months after the procedure, then annually. RESULTS: With a mean baseline volume of 15.7 +/- 11.7 mL, nodule volume decreased by 55.5% (6.5 +/- 5.7 mL) 4 years after LA (p < .01). Nodules had a significant decrease at 3 and 6 months, thereafter they remained stable, with an insignificant tendency to re-growth at 48 months. Thyroid functions and antibodies were unchanged throughout the follow-up. When dividing nodules into solid and spongiform, the former decreased at 6 months, remained stable up to 24 months, but showed a non-significant tendency to increase thereafter. Spongiform nodules progressively decreased up to 48 months. The difference in nodules' reduction between solid and spongiform nodules was significant from 3 months (p = .04) and became even more significant up to 48 months (p = .001). CONCLUSIONS: The LA technique succeeded in reducing thyroid nodules by about 50% at 4 years, but was more effective for spongiform than solid nodules. PMID- 27405596 TI - Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians. AB - BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs. PMID- 27405599 TI - Interpreting meta-analysis of continuous outcomes with pre and postvalues. PMID- 27405597 TI - Methane limit LPS-induced NF-kappaB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3beta-mediated IL-10 expression. AB - Inflammatory diseases such as sepsis and autoimmune colitis, characterized by an overwhelming activation of the immune system and the counteracting anti inflammatory response, remain a major health problem in worldwide. Emerging evidence suggests that methane have a protective effect on many animal models, like ischaemia reperfusion injury and diabetes-associated diseases. Whether methane could modulating inflammatory diseases remains largely unknown. Here we show that methane-rich saline (MS) ip treatment (16 ml/kg) alleviated endotoxin shock, bacteria-induced sepsis and dextran-sulfate-sodium-induced colitis in mice via decreased production of TNF-alpha and IL-6. In MS-treated macrophages, LPS induced activation of NF-kappab/MAPKs was attenuated. Interestingly, MS treatment significantly elevated the levels of IL-10 both in vitro and in vivo. Neutralization of IL-10 abrogated the therapeutic effect of MS. Moreover, anti IL10 blockade partially restored the MS-mediated attenuation of NF-kappab/MAPKs phosphorylation. We further found that MS resulted in markedly enhanced phosphorylation of GSK-3beta and AKT, which both mediate the release of Il-10. Additionally, inhibition of PI3K attenuated MS-mediated p-GSK-3beta and IL-10 production and reversed the suppressed activation of NF-kappab/ MAPKs in response to LPS. Our results reveal a novel effect and mechanisms of methane and support the potential value of MS as a therapeutic approach in innate inflammatory diseases. PMID- 27405600 TI - Pyramids are guides not rules: the evolution of the evidence pyramid. PMID- 27405601 TI - Current practice in neurocritical care of patients with subarachnoid haemorrhage and severe traumatic brain injury : Results of the Austrian Neurosurvey Study. AB - OBJECTIVES: The task force Neuroanaesthesia of the Austrian Society of Anaesthesiology, Resuscitation and Intensive Care Medicine (OGARI) is aiming to develop and provide recommendations in order to improve neurocritical care in Austria. Thus, a survey on neurocritical care concepts in Austria regarding intensive care of subarachnoid haemorrhage (SAH) and severe traumatic brain injury (TBI) was performed to assess the current status. METHODS: An online internet questionnaire comprising 59 items on current concepts of SAH and TBI critical care was sent to 117 anaesthesiology departments. RESULTS: The survey was answered by 30 (25.6 %) of the hospitals, 24 (80 %) of them treating patients with SAH and/or TBI. Data from ten SAH centres reveal that definitive care was achieved within 24 h in all hospitals; a case load >50 per year is noted in 70 % of intensive care units (ICU). In all, 50 % of departments employ written protocols for treatment. Regarding the treatment of TBI patients, 14 answers were received, indicating that 42.9 % of departments provide care for >50 patients per year. Time between arrival and CT scan is <30 min in all hospitals, and 28.6 % of departments rely on written protocols. Only 14.3 % of hospitals report about routine morbidity and mortality rounds. While the neurologic status is assessed at discharge from the ICU, there is no evaluation of 1-year outcome. CONCLUSIONS: Definitive care of SAH and TBI patients is achieved timely in Austria. When compared with SAH, more hospitals with lower case loads take care of TBI patients. Written guidelines and protocols at institutional level are often missing. Since routine morbidity and mortality conferences are sparse, and long term outcome is not assessed, there is room for improvement. PMID- 27405604 TI - Ginsenoside Re improves skin barrier function in HaCaT keratinocytes under normal growth conditions. AB - Ginsenoside Re (Re), a major ginsenoside of ginseng, enhanced the cornified cell envelope (CE) formation in HaCaT keratinocytes under normal conditions. In HaCaT keratinocytes, Re was also able to upregulate filaggrin protein and caspase-14 activity in a concentration-dependent manner. These findings reasonably imply that Re possesses a desirable property of improving skin barrier function. PMID- 27405602 TI - Lighting and marking policies are associated with reduced farm equipment-related crash rates: a policy analysis of nine Midwestern US states. AB - OBJECTIVE: To evaluate the effectiveness of roadway policies for lighting and marking of farm equipment in reducing crashes in Illinois, Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, South Dakota and Wisconsin. METHODS: In this ecological study, state policies on lighting and marking of farm equipment were scored for compliance with standards of the American Society of Agricultural and Biological Engineers (ASABE). Using generalized estimating equations negative binomial models, we estimated the relationships between lighting and marking scores, and farm equipment crash rates, per 100 000 farm operations. RESULTS: A total of 7083 crashes involving farm equipment was reported from 2005 to 2010 in the Upper Midwest and Great Plains. As the state lighting and marking score increased by 5 units, crash rates reduced by 17% (rate ratio=0.83; 95% CI 0.78 to 0.88). Lighting-only (rate ratio=0.48; 95% CI 0.45 to 0.51) and marking-only policies (rate ratio=0.89; 95% CI 0.83 to 0.96) were each associated with reduced crash rates. CONCLUSIONS: Aligning lighting and marking policies with ASABE standards may effectively reduce crash rates involving farm equipment. PMID- 27405603 TI - Nasopharyngeal bacterial carriage in young children in Greenland: a population at high risk of respiratory infections. AB - The incidence of childhood respiratory infections in Greenland is among the highest globally. We performed a population-based study of 352 Greenlandic children aged 0-6 years aiming to describe rates and risk factors for carriage of four key bacteria associated with respiratory infections, their antimicrobial susceptibility and inter-bacterial associations. Nasopharyngeal swabs were tested for Streptococcus pneumoniae grouped by serotypes included (VT) or not included (NVT) in the 13-valent pneumococcal conjugate vaccine, non-typable Haemophilus influenzae (NTHi), Staphylococcus aureus and Moraxella catarrhalis. S. pneumoniae was detected from age 2 weeks with a peak carriage rate of 60% in 2-year-olds. Young age and having siblings attending a daycare institution were associated with pneumococcal carriage. Overall co-colonization with ?2 of the studied bacteria was 52%. NTHi showed a positive association with NVT pneumococci and M. catarrhalis, respectively, M. catarrhalis was positively associated with S. pneumoniae, particular VT pneumococci, whereas S. aureus were negatively associated with NTHi and M. catarrhalis. Nasopharyngeal bacterial carriage was present unusually early in life and with frequent co-colonization. Domestic crowding increased odds of carriage. Due to important bacterial associations we suggest future surveillance of pneumococcal conjugate vaccine's impact on carriage in Greenland to also include other pathogens. PMID- 27405605 TI - Effects of salt stress imposed during two growth phases on cauliflower production and quality. AB - BACKGROUND: Cultivation of cauliflower is diffused in Mediterranean areas where water salinity results in the need to identify alternative irrigation sources or management strategies. Using saline water during two growth phases (from transplanting to visible appearance of inflorescence or from appearance of inflorescence to head harvest), the present study aimed to identify the growth period that is more suitable for irrigation with low quality water in relation to cauliflower production and quality. RESULTS: Salinity affected cauliflower growth mainly when imposed in the first growth phase. The growth reduction depended mainly on ion-specific effects, although slight nutrient imbalances as a result of Na+ and Cl- antagonisms were observed. The use of non-saline water in the first or second growth period reduced both the osmotic and toxic effects of salinity. When salinity was applied during inflorescence growth, yield was reduced because of a restriction of water accumulation in the head. CONCLUSION: The results of the present study demonstrate the possibility of producing marketable cauliflower heads under conditions of salinity by timing the application of the best quality water during the first growth phase to improve fruit quality and during the second phase to reduce the negative effects of salinity on yield. (c) 2016 Society of Chemical Industry. PMID- 27405606 TI - Sixty seconds on . . . road traffic crashes. PMID- 27405607 TI - Erratum to: Preservation of positional identity in fetus-derived neural stem (NS) cells from different mouse central nervous system compartments. PMID- 27405609 TI - Characterization and evaluation of antibacterial and antiproliferative activities of crude protein extracts isolated from the seed of Ricinus communis in Bangladesh. AB - BACKGROUND: Ricinus communis (Euphorbiaceae) has previously been reported to possess analgesic, antihistamine, antioxidant and anti-inflammatory activities. This study was designed for isolation, characterization and evaluation of antibacterial and anti-proliferative activities of R. communis seed protein. METHODS: The concentration and molecular weight of R. communis seed protein were estimated by SDS-PAGE and spectrophotometric analysis, respectively. Lectin activity was evaluated by hemagglutination assay on mice blood. In vitro susceptibility of four human pathogenic bacteria including Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes and Staphylococcus aureus was detected using disk diffusion assay, and minimum inhibitory concentration (MIC) value was determined using micro-dilution method. A total of twenty four Swiss albino mice containing Ehrlich's ascites carcinoma (EAC) cells were treated with the crude protein of R. communis at 50 and 100 MUg/ml/d/mouse for 6 days. Growth inhibitory activity of R. communis seed protein on EAC cells was determined by haemocytometer counting using trypan blue dye and DAPI (4?,6-diamidino-2 phenylindole) staining was used to assess apoptotic cells. RESULTS: The protein concentration of six R. communis (castor) varieties ranged between 21-35 mg/ml and molecular weight between 14-200 kDa. Castor protein agglutinated mice blood at 3.125 MUg/wall. The seed protein shows considerable antimicrobial activity against E. coli, P. aeruginosa and S. aureus, exhibiting MIC values of 250, 125 and 62.5 MUg/ml, respectively. Administration of seed protein led to 54 % growth inhibition of EAC cells at 100 MUg/ml. DAPI staining indicates marked features of apoptosis including condensation of cytoplasm, nuclear fragmentation and aggregation of apoptotic bodies etc. CONCLUSION: Our study suggests that the lectin rich R. communis seed protein has strong antibacterial and anticancer activities. PMID- 27405611 TI - Estimating time to event characteristics via longitudinal threshold regression models - an application to cervical dilation progression. AB - In longitudinal studies, it is sometimes of interest to estimate the distribution of the time a longitudinal process takes to traverse from one threshold to another. For example, the distribution of the time it takes a woman's cervical dilation to progress from 3 to 4 cm can aid the decision-making of obstetricians as to whether a stalled labor should be allowed to proceed or stopped in favor of other options. Often researchers treat this type of data structure as interval censored and employ traditional survival analysis methods. However, the traditional interval censoring approaches are inefficient in that they do not use all of the available data. In this paper, we propose utilizing a longitudinal threshold model to estimate the distribution of the elapsed time between two thresholds of the longitudinal process from repeated measurements. We extend this modeling framework to be used with multiple thresholds. A Wiener process under the first hitting time framework is used to represent survival distribution. We demonstrate our model through simulation studies and an analysis of data from the Consortium on Safe Labor study. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27405612 TI - Message from the Editor-in-Chief. PMID- 27405608 TI - Searching for convergent pathways in autism spectrum disorders: insights from human brain transcriptome studies. AB - Autism spectrum disorder (ASD) is one of the most heritable neuropsychiatric conditions. The complex genetic landscape of the disorder includes both common and rare variants at hundreds of genetic loci. This marked heterogeneity has thus far hampered efforts to develop genetic diagnostic panels and targeted pharmacological therapies. Here, we give an overview of the current literature on the genetic basis of ASD, and review recent human brain transcriptome studies and their role in identifying convergent pathways downstream of the heterogeneous genetic variants. We also discuss emerging evidence on the involvement of non coding genomic regions and non-coding RNAs in ASD. PMID- 27405613 TI - Female breast cancer burden was increasing during the 40 years in Hebei Province, China: a population-based study. AB - PURPOSE: The aim of our study was to estimate the female breast cancer burden and mortality trends in Hebei Province, China. METHODS: Eight population-based cancer registries in Hebei Province submitted cancer data to the Hebei Provincial cancer Registry Centre. All data were reviewed for quality and compiled for cancer statistics in 2011. The pooled data were stratified by area (urban/rural) and age group (0-4, 5-9, ..., 80+ years). Incidence and mortality rates were calculated and expressed per 100,000 persons. Proportions and ranks for breast cancer were calculated. Mortality data from 1973 to 1975, 1990 to 1992, and 2004 to 2005 were extracted from the national death surveys. Mortality and incidence data from Cixian and Shexian were obtained from population-based cancer registries in each county. RESULTS: The estimated numbers of newly diagnosed breast cancer cases and deaths from 2010 to 2011 were 26,028 and 5472, respectively. The CIR was 36.6/100,000. The ASIRW was 27.7/100,000, ranking the highest among all female cancers. The CMR was 7.7/100,000, and the ASMRW was 6.0/100,000, ranking fifth in female mortality. The ASMRW displayed an increasing trend in Hebei Province from 1973-1975 to 2010-2011, with a 53.7 % increase. In Cixian, the incidence rate increased with an annual percentage change (APC) of 7.7 %, and the mortality rate increased with an APC of 3.8 % from 1988 to 2011. Similar trends were observed for the incidence and mortality rates in Shexian, with APCs of 20.1 % and 11.0 %, respectively, from 2000 to 2011. CONCLUSION: Hebei Province experienced a heavy burden of breast cancer. The mortality rates increased during the past 40 years and the incidence and mortality trends may continue to increase in the next few years. PMID- 27405614 TI - Is fear perception special? Evidence at the level of decision-making and subjective confidence. AB - Fearful faces are believed to be prioritized in visual perception. However, it is unclear whether the processing of low-level facial features alone can facilitate such prioritization or whether higher-level mechanisms also contribute. We examined potential biases for fearful face perception at the levels of perceptual decision-making and perceptual confidence. We controlled for lower-level visual processing capacity by titrating luminance contrasts of backward masks, and the emotional intensity of fearful, angry and happy faces. Under these conditions, participants showed liberal biases in perceiving a fearful face, in both detection and discrimination tasks. This effect was stronger among individuals with reduced density in dorsolateral prefrontal cortex, a region linked to perceptual decision-making. Moreover, participants reported higher confidence when they accurately perceived a fearful face, suggesting that fearful faces may have privileged access to consciousness. Together, the results suggest that mechanisms in the prefrontal cortex contribute to making fearful face perception special. PMID- 27405615 TI - Neural response to pictorial health warning labels can predict smoking behavioral change. AB - In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants' self reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals' intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). PMID- 27405616 TI - Differential association of default mode network connectivity and rumination in healthy individuals and remitted MDD patients. AB - Rumination is associated with increased default-mode network (DMN) activity and functional connectivity (FC) in depressed and healthy individuals. In this study, we sought to examine the relationship between self-reported rumination and resting-state FC in the DMN and cognitive control networks in 25 remitted depressed patients and 25 matched healthy controls using independent component and seed-based analyses. We also explored potential group differences in the global pattern of resting-state FC. Healthy subjects with increased levels of rumination exhibited increased anterior DMN connectivity with the posterior DMN and the dorsal attention network and low connectivity within the anterior DMN. On the other hand, remitted depressed ruminators patients were associated with the opposite FC pattern in these regions. Based on global FC patterns, a support vector machine algorithm correctly classified 92% of the subjects into their respective group by a leave-one-out cross-validation. Whole-brain FC analysis also revealed a group by rumination interaction effect within the DMN. The present findings highlight the different functional roles of the anterior and the posterior DMN, and provide novel insights into the underlying neural mechanisms leading to depression relapse. PMID- 27405617 TI - Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology. AB - Childhood maltreatment (CM) has been associated with altered brain morphology, which may partly be due to a direct impact on neural growth, e.g. through the brain-derived neurotrophic factor (BDNF) pathway. Findings on CM, BDNF and brain volume are inconsistent and have never accounted for the entire BDNF pathway. We examined the effects of CM, BDNF (genotype, gene expression and protein level) and their interactions on hippocampus, amygdala and anterior cingulate cortex (ACC) morphology. Data were collected from patients with depression and/or an anxiety disorder and healthy subjects within the Netherlands Study of Depression and Anxiety (NESDA) (N = 289). CM was assessed using the Childhood Trauma Interview. BDNF Val66Met genotype, gene expression and serum protein levels were determined in blood and T1 MRI scans were acquired at 3T. Regional brain morphology was assessed using FreeSurfer. Covariate-adjusted linear regression analyses were performed. Amygdala volume was lower in maltreated individuals. This was more pronounced in maltreated met-allele carriers. The expected positive relationship between BDNF gene expression and volume of the amygdala is attenuated in maltreated subjects. Finally, decreased cortical thickness of the ACC was identified in maltreated subjects with the val/val genotype. CM was associated with altered brain morphology, partly in interaction with multiple levels of the BNDF pathway. Our results suggest that CM has different effects on brain morphology in met-carriers and val-homozygotes and that CM may disrupt the neuroprotective effect of BDNF. PMID- 27405618 TI - Dual antiplatelet and anticoagulant APAC prevents experimental ischemia reperfusion-induced acute kidney injury. AB - BACKGROUND: Renal ischemia-reperfusion predisposes to acute kidney injury (AKI) and mortality. APAC, mast cell heparin proteoglycan mimetic is a potent dual antiplatelet and anticoagulant inhibiting thrombosis in several vascular models. METHODS: Clinically relevant (0.06 and 0.13 mg/kg) and high (0.32 and 7.3 mg/kg) heparin doses of APAC and unfractionated heparin (UFH) were administered i.v. in pharmacological studies. Antithrombotic action of APAC and UFH was assessed with platelet aggregation to collagen, activated partial thromboplastin (APTT) and prothrombin (PT) times. Pharmacodynamics of [64Cu]-APAC or -UFH were monitored by PET/CT. Next, APAC and UFH doses (0.06 and 0.13 mg/kg) were i.v. administered 10 min prior to renal ischemia-reperfusion injury (IRI) in rats. RESULTS: APAC in contrast to UFH inhibited platelet aggregation. During 0.06 and 0.13 mg/kg dose regimens APTT and PT remained at baseline, but at the high APTT prolonged fourfold to sixfold. Overall bio-distribution and clearance of APAC and UFH were similar. After bilateral 30-min renal artery clamping, creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin concentrations and histopathology indicated faster renal recovery by APAC (0.13 mg/kg). APAC, unlike UFH, prevented expression of innate immune ligand hyaluronan and tubulointerstitial injury marker Kim-1. Moreover, in severe bilateral 1-h renal artery clamping, APAC (0.13 mg/kg) prevented AKI, as demonstrated both by biomarkers and survival. Compatible with kidney protection APAC reduced the circulating levels of vascular destabilizing and pro-inflammatory angiopoietin-2 and syndecan-1. No tissue bleeding ensued. CONCLUSION: APAC and UFH were similarly eliminated via kidneys and liver. In contrast to UFH, APAC (0.13 mg/kg) was reno-protective in moderate and even severe IRI by attenuating vascular injury and innate immune activation. PMID- 27405619 TI - Design and baseline characteristics of the LANDMARK study. AB - BACKGROUND: Calcium (Ca)-based phosphate (P) binders, compared to non-Ca-based P binders, contribute to vascular calcification, which is associated with cardiovascular events. METHODS: The LANDMARK study is a multicenter, randomized, open-label, parallel comparative study of lanthanum carbonate (LC) and calcium carbonate (CC) in hemodialysis patients. Stable hemodialysis patients with intact parathyroid hormone <=240 pg/mL meeting >=1 of the following criteria (age >65 years, postmenopause, diabetes mellitus) were randomized into the LC and CC groups. LC group patients initially received LC 750 mg/day or the previously used dose and were titrated up to a maximum 2250 mg/day to achieve serum P levels of 3.5-6.0 mg/dL. CC group patients received CC 3 g/day or the previously used dose and were titrated to achieve the same P range. If the target serum P level was not achieved, non-Ca-based P binders (other than LC) could also be added. The primary endpoint is survival time free of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction or stroke, and unstable angina. RESULTS: Overall, 2309 patients were allocated to the LC (N = 1154) or CC group (N = 1155). At baseline, the mean age was 68.4 years, 40.4 % were women, 55.9 % had diabetes, 18.3 % had a history of ischemic heart disease, and 13.9 % had cerebrovascular disease. A total of 184 patients (8.4 %) had undergone coronary intervention procedures. Baseline characteristics were well balanced between groups. CONCLUSIONS: The LANDMARK study will determine whether LC, a non Ca-based P binder, reduces cardiovascular mortality and morbidity in chronic hemodialysis patients. PMID- 27405620 TI - Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study. AB - BACKGROUND: Hyperuricemia is an established risk factor for cardiovascular events and mortality. This study investigated the association between serum uric acid and the incidence of nonfatal stroke in a Japanese community-based population. METHODS: We used a nationwide database of 155,322 subjects (aged 40-73, male 39 %) who participated in the annual "Specific Health Check and Guidance in Japan" checkup from 2008 to 2010. We examined the relationship between the quintiles of serum uric acid levels at baseline and the incidence of nonfatal stroke during a 2-year study period using self-reported data. RESULTS: The crude incidence of nonfatal stroke was significantly associated with serum uric acid levels at baseline, showing the lowest values in subjects with the 3rd quintile (Q3: men, 5.0-5.6; women, 3.8-4.3) of uric acid levels (mg/dL) and the highest values in subjects with the highest quintile (Q5: men >=7.1, women >=5.5) both in men and women (P < 0.05). In multivariate-adjusted logistic regression analysis, the odds ratio (OR) of the Q5 group was significantly higher than for the Q3 group in both men and women [men: OR 1.26, 95 % confidence interval (CI) 1.04-1.54, women: OR 1.24, 95 % CI 1.00-1.48]. In the subgroup analysis, the OR of the Q5 group of uric acid levels for incident stroke was high, irrespective of characteristics such as age, sex, and renal function. CONCLUSIONS: This study has shown that serum uric acid is independently associated with the incidence of nonfatal stroke in the general Japanese population. PMID- 27405640 TI - Cutoff Scores for MMPI-2 and MMPI-2-RF Cognitive-Somatic Validity Scales for Psychometrically Defined Malingering Groups in a Military Sample. AB - OBJECTIVE: This research examined cutoff scores for MMPI-2 and MMPI-2-RF validity scales specifically developed to assess non-credible reporting of cognitive and/or somatic symptoms. The validity scales examined included the Response Bias Scale (RBS), the Symptom Validity Scales (FBS, FBS-r), Infrequent Somatic Responses scale (Fs), and the Henry-Heilbronner Indexes (HHI, HHI-r). METHOD: Cutoffs were developed by comparing a psychometrically defined non-malingering group with three psychometrically defined malingering groups (probable, probable to definite, and definite malingering) and a group that combined all malingering groups. The participants in this research were drawn from a military sample consisting largely of patients with traumatic brain injury (mostly mild traumatic brain injury). RESULTS: Specificities for cutoffs of at least 0.90 are provided. Sensitivities, predictive values, and likelihood ratios are also provided. CONCLUSIONS: RBS had the largest mean effect size (d) when the malingering groups were compared to the non-malingering group (d range = 1.23-1.58). PMID- 27405639 TI - Periodontal bacterial colonization in synovial tissues exacerbates collagen induced arthritis in B10.RIII mice. AB - BACKGROUND: It has been previously hypothesized that oral microbes may be an etiological link between rheumatoid arthritis (RA) and periodontal disease. However, the mechanistic basis of this association is incompletely understood. Here, we investigated the role of periodontal bacteria in induction of joint inflammation in collagen-induced arthritis (CIA) in B10.RIII mice. METHODS: CIA prone B10.RIII mice were infected orally with a polybacterial mixture of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia for 24 weeks before induction of CIA. The ability of polybacterial mixture to colonize the periodontium and induce systemic response, horizontal alveolar bone resorption in infected B10.RIII mice was investigated. Arthritis incidence, severity of joint inflammation, pannus formation, skeletal damage, hematogenous dissemination of the infection, matrix metalloproteinase 3 (MMP3) levels, and interleukin-17 expression levels were evaluated. RESULTS: B10.RIII mice had gingival colonization with all three bacteria, higher levels of anti-bacterial immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies, significant alveolar bone resorption, and hematogenous dissemination of P. gingivalis to synovial joints. Infected B10.RIII mice had more severe arthritis, and higher serum matrix metalloproteinase 3 levels and activity. Histopathological analysis showed increased inflammatory cell infiltration, destruction of articular cartilage, erosions, and pannus formation. Additionally, involved joints showed had expression levels of interleukin-17. CONCLUSION: These findings demonstrate that physical presence of periodontal bacteria in synovial joints of B10.RIII mice with collagen-induced arthritis is associated with arthritis exacerbation, and support the hypothesis that oral bacteria, specifically P. gingivalis, play a significant role in augmenting autoimmune arthritis due to their intravascular dissemination to the joints. PMID- 27405642 TI - Letter to the editor regarding the article 'The abdominal whirlpool sign'. PMID- 27405643 TI - Does IV contrast extravasation on CT in anticoagulant-related rectus sheath and iliopsoas hematoma predict hematoma expansion and patient outcomes? AB - OBJECTIVE: The purpose of the study was to evaluate if IV contrast extravasation on CT in anticoagulant-related rectus sheath and iliopsoas hematoma predict hematoma expansion and patient outcomes. MATERIALS AND METHODS: All patients presented with anticoagulation-related spontaneous IP hematoma or RS hematoma and who underwent contrast-enhanced CT exploration, with injection of a contrast material, from January 2012 to January 2015 in our institution were included in this study. Considering the retrospective nature of our study, our institutional review board judged our study to be exempted from ethical approval and no patient consent was required. Computed tomography (CT) images were retrospectively analyzed blindly of the evolution and treatment of hematomas. The type of muscle involved; the presence of contrast extravasation after contrast injection; the volume of the hematoma, as well as, clinical and biological results (hemoglobin value g/dL); and for each patient, the type of anticoagulation used, patient's treatment and outcomes were noted. The analyses were conducted using R 3.1.0. All statistical tests were 2-sided, and probability values <0.05 were regarded as significant. RESULTS: Sixty-eight patients were reviewed. Among 68 patients, 44 (65%) patients presented spontaneous IP hematoma and 24/68 (35%) a RS hematoma. There were 37 men (54%) and 31 (46%) women, ranging from 39 to 93 years with a median age of 75 years. Hemodynamic instability was statistically associated with IP hematomas and large volume of hematoma (p < 0.001). Only 15 patients had follow-up CT, 10 without and with IV contrast, 2 with IV contrast only, and 3 without contrast. Follow-up CT was performed from J0 to J8. Detection of contrast extravasation did not appear related to hemodynamically instability (p = 0.35), to a neurological deficit (p = 1), or to the increase in the volume of the hematoma on follow-up CT (p = 0.81). The different types of anticoagulant were not related to muscular type more than the other (p = 0.9). Among anticoagulant therapy, only vitamin K antagonist therapy was statistically associated with surgery (p = 0.04). CONCLUSION: CT extravasation of contrast material in IP and RS hematoma does not appear to be related with clinical criteria of severity, and therefore should not be solely considered as a radiological decision criteria. PMID- 27405644 TI - Serrated polyps are detected at CT colonography: clinical observations over the past decade and results from CTC-based screening of average risk adults. PMID- 27405641 TI - alphaE-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development. AB - Embryonic signalling centres are specialized clusters of non-proliferating cells that direct the development of many organs. However, the mechanisms that establish these essential structures in mammals are not well understood. Here we report, using the murine incisor as a model, that alphaE-catenin is essential for inhibiting nuclear YAP localization and cell proliferation. This function of alphaE-catenin is required for formation of the tooth signalling centre, the enamel knot (EK), which maintains dental mesenchymal condensation and epithelial invagination. EK formation depends primarily on the signalling function of alphaE catenin through YAP and its homologue TAZ, as opposed to its adhesive function, and combined deletion of Yap and Taz rescues the EK defects caused by loss of alphaE-catenin. These findings point to a developmental mechanism by which alphaE catenin restricts YAP/TAZ activity to establish a group of non-dividing and specialized cells that constitute a signalling centre. PMID- 27405645 TI - FDG-PET/CT lymph node staging after neoadjuvant chemotherapy in patients with adenocarcinoma of the esophageal-gastric junction. AB - OBJECTIVES: The aim of the analysis was to assess the accuracy of various FDG PET/CT parameters in staging lymph nodes after neoadjuvant chemotherapy. METHODS: In this prospective study, 74 patients with adenocarcinoma of the esophageal gastric junction were examined by FDG-PET/CT in the course of their neoadjuvant chemotherapy given before surgical treatment. Data from the final FDG-PET/CT examinations were compared with the histology from the surgical specimens (gold standard). The accuracy was calculated for four FDG-PET/CT parameters: (1) hypermetabolic nodes, (2) large nodes, (3) large-and-medium large nodes, and (4) hypermetabolic or large nodes. RESULTS: In 74 patients, a total of 1540 lymph nodes were obtained by surgery, and these were grouped into 287 regions according to topographic origin. Five hundred and two nodes were imaged by FDG-PET/CT and were grouped into these same regions for comparison. In the analysis, (1) hypermetabolic nodes, (2) large nodes, (3) large-and-medium large nodes, and (4) hypermetabolic or large nodes identified metastases in particular regions with sensitivities of 11.6%, 2.9%, 21.7%, and 13.0%, respectively; specificity was 98.6%, 94.5%, 74.8%, and 93.6%, respectively. The best accuracy of 77.7% reached the parameter of hypermetabolic nodes. Accuracy decreased to 62.0% when also smaller nodes (medium-large) were taken for the parameter of metastases. CONCLUSIONS: FDG-PET/CT proved low sensitivity and high specificity. Low sensitivity was based on low detection rate (32.6%) when compared nodes imaged by FDG-PET/CT to nodes found by surgery, and in inability to detect micrometastases. Sensitivity increased when also medium-large LNs were taken for positive, but specificity and accuracy decreased. PMID- 27405646 TI - Transgression and Gender. AB - Human activity is determined to a great extent by not only biological sex but also gender. The aim of the study was to examine relationships between transgression and types of gender. A population of 558 individuals (399 women and 159 men) aged 19-25 (mean age: 22.6) were studied. The age of the women ranged from 19 to 24 (mean age: 22.4) and of the men-from 19 to 25 (mean age: 22.8). In order to examine the intensity of transgression, the Polish version of the chronic self-destructiveness scale was applied. The gender was studied by means of the Polish version of the Bem sex role inventory. Androgynous women achieved the highest and feminine men-the lowest scores on the transgression scale. In women, the masculinity scale positively correlated with the transgression scale, whereas the femininity scale did not significantly correlate with transgression, although the coefficient was negative. No statistically significant correlations were found in men (although the coefficients were positive). Biological sex and gender were qualitative variables that differentiated the intensity of transgression. Equilibrium between the psychological dimension of femininity and the psychological dimension of masculinity was vital for transgressive tendencies, particularly in women. Androgynous women showed rather the adaptive aspect of transgression. PMID- 27405647 TI - Are disparities of waiting times for breast cancer care related to socio-economic factors? A regional population-based study (France). AB - The increasing number of breast cancer cases may induce longer waiting times (WT), which can be a source of anxiety for patients and may play a role in survival. The aim of this study was to examine the factors, in particular socio economic factors, related to treatment delays. Using French Cancer Registry databases and self-administered questionnaires, we included 1,152 women with invasive non-metastatic breast cancer diagnosed in 2007. Poisson regression analysis was used to identify WTs' influencing factors. For 973 women who had a malignant tissue sampling, the median of overall WT between the first imaging procedure and the first treatment was 44 days (9 days for pathological diagnostic WT and 31 days for treatment WT). The medical factors mostly explained inequalities in WTs. Socio-economic and behavioral factors had a limited impact on WTs except for social support which appeared to be a key point. Better identifying the factors associated with increase in WTs will make it possible to develop further interventional or prospective studies to confirm their causal role in delay and at last reduce disparities in breast cancer management. PMID- 27405648 TI - Uptake of HIV testing and counseling, risk perception and linkage to HIV care among Thai university students. AB - BACKGROUND: HIV testing and counseling (HTC) with linkage to care after known infection are key components for HIV transmission prevention. This study was conducted to assess HTC uptake, HIV risk perception and linkage to care among Thai university students. METHODS: An outreach HTC program was conducted in a large public university in Thailand from January 2013 to December 2014. The program consisted of brief HIV knowledge assessment, free HTC, HIV risk assessment and education provided by the healthcare personnel. Students were categorized into low, moderate and high-risk groups according to the pre-defined HIV risk characteristics. RESULTS: One-thousand-eight-hundred-one students participated in the program, 494 (27 %) underwent HTC. Independent characteristics associated with no HTC uptake included female sex (P < 0.001), lower HIV knowledge score (P < 0.001), younger age (P < 0.001) and students from non-health science faculties (P = 0.02). Among the 494 students undergoing HTC, 141 (29 %) were categorized into moderate or high-risk group, of whom 45/141 (32 %) had false perception of low HIV risk. Being heterosexual was independently associated with false perception of low HIV risk (P = 0.04). The rate of new HIV infection diagnosis was 4/494 (0.8 %). Of these 4 HIV-infected students, 3 (75 %) were men who have sex with men and only 2 of the 4 students (50 %) showed up for HIV continuity care. CONCLUSIONS: An outreach HIV prevention program with HTC was feasible and beneficial in detecting HIV risk and infection among the university students. However, interventions to improve HTC uptake, HIV risk perception and linkage to care are needed. PMID- 27405649 TI - Identification of specific residues in avian influenza A virus NS1 that enhance viral replication and pathogenicity in mammalian systems. AB - Reassortment of their segmented genomes allows influenza A viruses (IAV) to gain new characteristics, which potentially enable them to cross the species barrier and infect new hosts. Improved replication was observed for reassortants of the strictly avian IAV A/FPV/Rostock/34 (FPV, H7N1) containing the NS segment from A/Goose/Guangdong/1/1996 (GD, H5N1), but not for reassortants containing the NS segment of A/Mallard/NL/12/2000 (MA, H7N3). The NS1 of GD and MA differ only in 8 aa positions. Here, we show that efficient replication of FPV-NSMA-derived mutants was linked to the presence of a single substitution (D74N) and more prominently to a triple substitution (P3S+R41K+D74N) in the NS1MA protein. The substitution(s) led to (i) increased virus titres, (ii) larger plaque sizes and (iii) increased levels and faster kinetics of viral mRNA and protein accumulation in mammalian cells. Interestingly, the NS1 substitutions did not affect viral growth characteristics in avian cells. Furthermore, we show that an FPV mutant with N74 in the NS1 (already possessing S3+K41) is able to replicate and cause disease in mice, demonstrating a key role of NS1 in the adaptation of avian IAV to mammalian hosts. Our data suggest that (i) adaptation to mammalian hosts does not necessarily compromise replication in the natural (avian) host and (ii) very few genetic changes may pave the way for zoonotic transmission. The study reinforces the need for close surveillance and characterization of circulating avian IAV to identify genetic signatures that indicate a potential risk for efficient transmission of avian strains to mammalian hosts. PMID- 27405650 TI - How Well Do They Convert? Trending ASAPS Presentations to Publication From 1995 2010. AB - BACKGROUND: The American Society for Aesthetic Plastic Surgery (ASAPS) sponsors an annual conference that promotes education, advocacy, and care. There, researchers deliver abstracts as podium and poster presentations. Subsequently, ASAPS encourages submitting these research findings for publication. Yet, many never become published manuscripts. OBJECTIVES: To quantify the conversion rates of oral abstract presentations to publication from 1995 to 2010. Secondary objectives included evaluating trends in presentations, publications, time to publication, and published journal distribution. METHODS: Comprehensive literature search in PubMed cross-referencing oral abstract presentations and determining peer-reviewed publication status. The conversion rate and time to publication was calculated. RESULTS: A total of 569 oral presentations met the inclusion criteria. The mean annual presentations was 35.6. A total of 360 presentations became journal publications. The mean annual publications was 22.5. The mean conversion rate was 63.3% (R2, 0.1271; P-value of .23). The mean time to publication was 19.8 months. Most publications occurred within two years of presentation (87.5%). Publications appeared in Plastic and Reconstructive Surgery (PRS, 48.6%), Aesthetic Surgery Journal (ASJ, 27.8%), Aesthetic Plastic Surgery (APS, 5.6%), Annals of Plastic Surgery (AnnPS, 4.2%), Clinics in Plastic Surgery (CPS, 3.9%), and other journals (10%). Trending ASJ publications vs other journals in five year intervals demonstrated an increase from 18.7% to 58.8%. CONCLUSIONS: While the number of presentations and publications declined, the time to publication, and conversion rate remained largely the same. Despite its short existence, ASJ became the predominant journal publishing ASAPS abstracts by the end of the study period. PMID- 27405651 TI - Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. AB - Discordance in estrogen (ER), progesterone (PR), and HER2/neu status between primary breast tumours and metastatic disease is well recognized. In this review, we highlight how receptor discordance between primary tumours and paired metastasis can help elucidate the mechanism of metastasis but can also effect patient management and the design of future trials. Discordance rates and ranges were available from 47 studies (3384 matched primary and metastatic pairs) reporting ER, PR, and HER2/neu expression for both primary and metastatic sites. Median discordance rates for ER, PR, and HER2/neu were 14 % (range 0-67 %, IQR 9 25 %), 21 % (range 0-62 %, IQR 15-41 %), and 10 % (range 0-44 %, IQR 4-17 %), respectively. Loss of receptor expression was more common (9.17 %) than gain (4.51 %). Discordance rates varied amongst site of metastasis with ER discordance being highest in bone metastases suggesting that discordance is a true biological phenomenon. Discordance rates vary for both the biomarker and the metastatic site. Loss of expression is more common than gain. This can affect patient management as it can lead to a reduction in both the efficacy and availability of potential therapeutic agents. Future studies are recommended to explore both the mechanisms of discordance as well as its impact on patient outcome and management. PMID- 27405652 TI - Relative impact of COPD and comorbidities on generic health-related quality of life: a pooled analysis of the COSYCONET patient cohort and control subjects from the KORA and SHIP studies. AB - BACKGROUND: Health-related quality of life (HRQL) is an important patient reported outcome measure used to describe the burden of chronic obstructive pulmonary disease (COPD) which is often accompanied by comorbid conditions. METHODS: Data from 2275 participants in the COPD cohort COSYCONET and from 4505 lung-healthy control subjects from the population-based KORA and SHIP studies were pooled. Main outcomes were the five dimensions of the generic EQ-5D-3 L questionnaire and two EQ-5D index scores using a tariff based on valuations from the general population and an experience-based tariff. The association of COPD in GOLD grades 1-4 and of several comorbid conditions with the EQ-5D index scores was quantified by multiple linear regression models while adjusting for age, sex, education, body mass index (BMI), and smoking status. RESULTS: For all dimensions of the EQ-5D, the proportion of participants reporting problems was higher in the COPD group than in control subjects. COPD was associated with significant reductions in the EQ-5D index scores (-0.05 points for COPD grades 1/2, -0.09 for COPD grade 3, -0.18 for COPD grade 4 according to the preference-based utility tariff, all p < 0.0001). Adjusted mean index scores were 0.89 in control subjects and 0.85, 0.84, 0.81, and 0.72 in COPD grades 1-4 according to the preference based utility tariff and 0.76, 0.71, 0.68, 0.64, and 0.58 for control subjects and COPD grades 1-4 for the experience-based tariff respectively. Comorbidities had additive negative effects on the index scores; the effect sizes for comorbidities were comparable to or smaller than the effects of COPD grade 3. No statistically significant interactions between COPD and comorbidities were observed. Score differences between COPD patients and control subjects were most pronounced in younger age groups. CONCLUSIONS: Compared with control subjects, the considerable reduction of HRQL in patients with COPD was mainly due to respiratory limitations, but observed comorbidities added linearly to this effect. Younger COPD patients showed a greater loss of HRQL and may therefore be in specific need of comprehensive disease management. TRIAL REGISTRATION: NCT01245933. PMID- 27405654 TI - Tropical grasslands: A pivotal place for a more multi-functional agriculture. AB - Tropical grasslands represent a pivotal arena for the sustainable intensification of agriculture in the coming decades. The abundant ecosystem services provided by the grasslands, coupled with the aversion to further forest destruction, makes sustainable intensification of tropical grasslands a high policy priority. In this article, we provide an inventory of agricultural initiatives that would contribute to the sustainable intensification of the tropical grassland agro ecosystem, and we recommend a shift in the scientific priorities of animal scientists that would contribute to realization of a more agro-ecological and multi-functional agriculture in the world's tropical grasslands. PMID- 27405653 TI - Sustainable intensification of agriculture for human prosperity and global sustainability. AB - There is an ongoing debate on what constitutes sustainable intensification of agriculture (SIA). In this paper, we propose that a paradigm for sustainable intensification can be defined and translated into an operational framework for agricultural development. We argue that this paradigm must now be defined-at all scales-in the context of rapidly rising global environmental changes in the Anthropocene, while focusing on eradicating poverty and hunger and contributing to human wellbeing. The criteria and approach we propose, for a paradigm shift towards sustainable intensification of agriculture, integrates the dual and interdependent goals of using sustainable practices to meet rising human needs while contributing to resilience and sustainability of landscapes, the biosphere, and the Earth system. Both of these, in turn, are required to sustain the future viability of agriculture. This paradigm shift aims at repositioning world agriculture from its current role as the world's single largest driver of global environmental change, to becoming a key contributor of a global transition to a sustainable world within a safe operating space on Earth. PMID- 27405655 TI - Di (2-ethylhexyl) phthalate impairs steroidogenesis in ovarian follicular cells of prepuberal mice. AB - Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer which is widely used in the manufacture of plastics. As a common environmental contaminant and recognized endocrine disrupting chemical, DEHP is able to deregulate the functions of a variety of tissues, including the reproductive system both in males and females. In order to investigate the possible effects of DEHP on the first wave of folliculogenesis, occurring in the mouse ovary postnatally, mice were administered 20 or 40 MUg/kg DEHP through intraperitoneal injection at days 5, 10 and 15 post partum (dpp). Following DEHP treatment the gene expression profile of control and exposed ovaries was compared by microarray analyses at 20 dpp. We found that in the exposed ovaries DEHP significantly altered the transcript levels of several immune response and steroidogenesis associated genes. In particular, DEHP significantly decreased the expression of genes essential for androgen synthesis by theca cells including Lhcgr, Cyp17a1, Star and Ldlr. Immunohistochemistry and immune flow cytometry confirmed reduced expression of LHCGR and CYP17A1 proteins in the exposed theca cells. These effects were associated to a significant reduction in ovarian concentrations of progesterone, 17beta-estradiol and androstenedione along with a reduction of LH in the serum. Although we did not find a significant reduction of the number of primary, secondary or antral follicles in the DEHP exposed ovaries when compared to controls, we did observe that theca cells showed an altered structure of the nuclear envelope, fewer mitochondria, and mitochondria with a reduced number of cristae. Collectively, these results demonstrate a deleterious effect of DEHP exposure on ovarian steroidogenesis during the first wave of folliculogenesis that could potentially affect the correct establishment of the hypothalamic pituitary-ovarian axis and the onset of puberty. PMID- 27405657 TI - Linquats: Synthesis, Characterization, and Properties of Linear Extended Diquats. AB - We report an innovative synthetic route to linear extended diquats (linquats). Our approach is short and efficient and features a highly modular reaction sequence based on two-fold quaternization followed by the key intramolecular [2+2+2] alkyne cycloaddition. The physico-chemical properties of four new linquats were characterized by spectroscopic methods, X-ray crystallography, and electrochemistry complemented by information obtained from DFT calculations. Electron deficient N-heteroaromatic cations with linear extended diquat motif with high electron affinities have been recently recognized as attractive n-type semiconductors for chemical and biological sensing. Their advantageous redox properties such as very fast reversible electron transfers make the title compounds interesting for applications. PMID- 27405656 TI - Glucuronidation of 4-tert-octylphenol in humans, monkeys, rats, and mice: an in vitro analysis using liver and intestine microsomes. AB - 4-tert-Octylphenol (4-tOP) is an endocrine-disrupting chemical. It is mainly metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the glucuronidation of 4-tOP in humans, monkeys, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of 4-tOP glucuronidation by liver microsomes followed the Michaelis Menten model for humans and monkeys, and the biphasic model for rats and mice. The K m, V max, and CL int values of human liver microsomes were 0.343 uM, 11.6 nmol/min/mg protein, and 33.8 mL/min/mg protein, respectively. The kinetics of intestine microsomes followed the Michaelis-Menten model for humans, monkeys, and rats, and the biphasic model for mice. The K m, V max, and CL int values of human intestine microsomes were 0.743 uM, 0.571 nmol/min/mg protein, and 0.770 mL/min/mg protein, respectively. The CL int values estimated by Eadie-Hofstee plots were in the order of mice (high-affinity phase) (3.0) > humans (1.0) >= monkeys (0.9) > rats (high-affinity phase) (0.4) for liver microsomes, and monkeys (10) > mice (high-affinity phase) (5.6) > rats (1.4) > humans (1.0) for intestine microsomes. The percentages of the CL int values of intestine microsomes to liver microsomes were in the order of monkeys (27 %) > rats (high affinity phase in liver microsomes) (7.9 %) > mice (high-affinity phase in liver and intestine microsomes) (4.2 %) > humans (2.3 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward 4-tOP markedly differ among species and imply that species differences are strongly associated with the toxicities of alkylphenols. PMID- 27405658 TI - How much information about the benefits of medicines is included in patient leaflets in the European Union? - A survey. AB - INTRODUCTION: Patient information leaflets (PILs) are required with all licensed medicines throughout the European Union (EU) and they must include information about all side effects and their likelihood. This has led to criticism of a lack of balance, with little information included about potential benefits. Recent European Medicines Agency guidance proposed the inclusion of benefit information, and this study examined the current prevalence and type of such information in PILs in the EU. METHODS: A survey and content analysis of the English translation of PILs in the EUwas carried out. Random quota sampling was used on the most frequently dispensed (n = 50) and newly licensed medicines (n = 50) in 2011/2. Leaflets were searched for benefit information meeting predefined criteria, and data synthesised and categorised into 10 categories. RESULTS: Eighty-five (85%) leaflets described how the medicine works, with 45 providing information about the rationale for treatment (more commonly for newly licensed (32/50) than most commonly dispensed medicines (13/50; P < 0.001). Nearly half (47) did not describe whether the medicine was curative, symptomatic or preventative. The terms used to communicate uncertainty were imprecise (such as 'may help'). None communicated numerical benefit information. CONCLUSION: Current PILs do not appropriately communicate information about benefit. At the basic level, around a half did not include information about treatment rationale or whether the treatment was to treat symptoms, curative or preventative. However, for true informed decision making, patients need quantitative information about benefits and none of the leaflets provided this. PMID- 27405659 TI - Celiac patients' attitudes regarding novel therapies. AB - BACKGROUND: The only current treatment for celiac disease (CD) is a gluten-free diet (GFD). Novel therapies are in development to supplement or replace a GFD. Knowledge of patients' attitudes toward these therapies is limited. The aim of this study was to determine attitudes about novel therapies in securely diagnosed patients with CD on a GFD and to correlate factors associated with these attitudes. METHODS: A survey was created with two scenarios: a novel therapy that protects against cross contamination while on a GFD and one that allows intentional gluten consumption. The survey also included the Celiac Dietary Adherence Test and the CD Quality of Life (QOL) surveys. RESULTS: A total of 182/284 (64%) CD patients completed the survey. Significantly more respondents would take a novel therapy to protect against cross contamination compared with one that allows intentional gluten consumption (87% vs. 65%; P<0.001). This difference was significant among women but not men. In both scenarios, protection against bowel inflammation was significantly more important than symptom control, and side effects were more important than cost. For a novel therapy that would allow intentional gluten consumption, a one-time injection was preferred over a daily pill, and patients willing to take this therapy had significantly lower QOL scores. CONCLUSIONS: CD patients on a GFD are interested in novel therapies. There were notable differences in attitudes by gender and QOL. Considering patient preferences, drugs with daily or less frequent dosing that protect against bowel inflammation from gluten cross contamination would be best accepted. PMID- 27405660 TI - HIV Care Nurses' Knowledge of HIV Criminalization: A Feasibility Study. AB - HIV-related criminal laws in some jurisdictions may hamper population health efforts to manage HIV and bring about an AIDS-free generation. HIV care nurses have an instrumental role to play in ensuring equitable care and health for all in a context of HIV. The purpose of our study was to determine HIV care nurses' knowledge of HIV-related criminal laws. Ecosocial theory and content expert opinion guided development of a questionnaire to assess nurses' knowledge of HIV related criminal laws. A total of 174 HIV care nurses from Canada (n = 23) and the United States (n = 151) completed the questionnaire. Knowledge gaps were observed in several aspects of HIV-related criminal laws that can influence nursing clinical practices. Nurses should increase their knowledge of HIV-related criminal laws to ensure the success of population health initiatives and to reduce stigma and discrimination experienced by people living with HIV. PMID- 27405661 TI - Associations between strain, herd size, age at first calving, culling reason and lifetime performance characteristics in Holstein-Friesian cows. AB - Cow longevity and lifetime performance traits are good indicators of breeding effectiveness and animal welfare. They are also interrelated with the economics of dairy herd. Unfortunately, a high milk yield is often associated with deteriorated cow health and fertility and, consequently, with an increased culling rate. This situation, observed also in the Polish population of Holstein Friesian cattle, inspired us to undertake a study on the associations between some factors and lifetime performance characteristics. The data set consisted of the records on 135 496 cows, including 131 526 of the Black and White strain (BW), and 3970 of the Red and White strain (RW) covered by performance recording and culled in 2012. It was found that cows of the BW strain and those from the largest herds (>100 cows) reached higher lifetime and mean daily energy-corrected milk (ECM) yields than cows of the RW strain and those from smaller herds culled at a similar age. Cows youngest at first calving (<2.0 years) were characterised by the highest lifetime ECM yield. It indicates that heifers can be bred even when they are younger than 15 to 16 months with no significant negative effect on their later performance. Infertility and reproduction problems (39.6%) and udder diseases (15.5%) constituted the most frequent reasons for cow culling. Cow longevity and lifetime productivity were considerably affected by the interactions between the studied factors. PMID- 27405662 TI - Load analysis of a patellofemoral joint by a quadriceps muscle. AB - PURPOSE: The aim of this paper is to develop a model of the patellofemoral joint by considering the linear displacement along axis of cylindrical joint and to use this model in the analysis of the femur spatial displacements caused by the quadriceps muscle force. METHOD: The linear displacement along the axis of cylindrical joint of the patellofemoral joint is computed using optimization methods - minimization of the difference between the modeled and measured spatial displacements of the femur with respect to the tibia over the full range of the knee flexion. Then, the instantaneous screw displacements of the femur with regard to the tibia and corresponding muscle forces are computed for the model developed. The moment of the force arm with respect to the vector of screw displacement is used to evaluate the effectiveness of the acting force. RESULTS: The simulation results for the model developed show significant improvement of the modeled linear coordinates of the femur reference system with respect to tibia reference system. The displacement analysis of the femur loaded by quadriceps muscle force can be used to describe the patellofemoral dislocation problem. CONCLUSIONS: The model of the patella- femur joint where the linear displacement along axis of the cylindrical joint is considered can reproduce the actual patella displacements more accurately. It seems expedient to study elasto statics problem of this mechanism. The model can be used to study some medical conditions such as patellofemoral dislocation. PMID- 27405663 TI - A rare gamma-pyranopyrazole skeleton: design, one-pot synthesis and computational study. AB - Drawing upon a consecutive amide coupling and intramolecular cyclisation pathway, a one-pot, straightforward synthetic route has been developed for a range of pyrazole fused gamma-pyrone derivatives. The reaction mechanism proposed for the chemoselective formation of gamma-pyranopyrazole is furthermore fully supported by experimental and computational studies. PMID- 27405664 TI - Linear dependence of surface expansion speed on initial plasma temperature in warm dense matter. AB - Recent progress in laser-driven quasi-monoenergetic ion beams enabled the production of uniformly heated warm dense matter. Matter heated rapidly with this technique is under extreme temperatures and pressures, and promptly expands outward. While the expansion speed of an ideal plasma is known to have a square root dependence on temperature, computer simulations presented here show a linear dependence of expansion speed on initial plasma temperature in the warm dense matter regime. The expansion of uniformly heated 1-100 eV solid density gold foils was modeled with the RAGE radiation-hydrodynamics code, and the average surface expansion speed was found to increase linearly with temperature. The origin of this linear dependence is explained by comparing predictions from the SESAME equation-of-state tables with those from the ideal gas equation-of-state. These simulations offer useful insight into the expansion of warm dense matter and motivate the application of optical shadowgraphy for temperature measurement. PMID- 27405667 TI - Water-The Most Anomalous Liquid. PMID- 27405665 TI - Therapeutic targeting of myeloid-derived suppressor cells involves a novel mechanism mediated by clusterin. AB - Myeloid-derived suppressor cells (MDSCs) constitute a key checkpoint that impedes tumor immunity against cancer. Chemotherapeutic intervention of MDSCs has gained ground as a strategy for cancer therapy but its mechanism remains obscure.We report here a unique mechanism by which monocytic (M)-MDSCs are spared, allowing them to polarize towards M1 macrophages for reactivation of immunity against breast cancer. We first demonstrated that curcumin, like docetaxel (DTX), can selectively target CD11b(+)Ly6G(+)Ly6C(low) granulocytic (G)-MDSCs, sparing CD11b(+)Ly6G(-)Ly6C(high) M-MDSCs, with reduced tumor burden in 4T1-Neu tumor bearing mice. Curcumin treatment polarized surviving M-MDSCs toward CCR7(+) Dectin-1(-)M1 cells, accompanied by IFN-gamma production and cytolytic function in T cells. Selective M-MDSC chemoresistence to curcumin and DTX was mediated by secretory/cytoplasmic clusterin (sCLU). sCLU functions by trapping Bax from mitochondrial translocation, preventing the apoptotic cascade. Importantly, sCLU was only found in M-MDSCs but not in G-MDSCs. Knockdown of sCLU in M-MDSCs and RAW264.7 macrophages was found to reverse their natural chemoresistance. Clinically, breast cancer patients possess sCLU expression only in mature CD68(+) macrophages but not in immature CD33(+) immunosuppressive myeloid cells infiltrating the tumors. We thus made the seminal discovery that sCLU expression in M-MDSCs accounts for positive immunomodulation by chemotherapeutic agents. PMID- 27405668 TI - Rethinking events in the haemostatic process: role of factor V and TFPI. AB - Regulatory mechanisms responsible for limiting blood clot formation are critical for maintaining normal haemostasis. Dysregulation can lead to bleeding (e.g. haemophilia) or thrombosis. New findings showing that tissue factor pathway inhibitor-alpha (TFPIalpha) binds coagulation factor V(a) and inhibits prothrombinase assembly highlights that our understanding of the initiation of coagulation is evolving. Work over the past decade on the biochemistry of FV activation has laid the groundwork for deciphering the mechanistic bases that may underpin how TFPIalpha mediates these anticoagulant effects. Collectively, these new findings are re-shaping our thinking about how coagulation is initiated at the site of injury. These ideas could have important clinical implications and help identify new ways to bias the coagulation response for the treatment of haemophilia and other disorders of the haemostatic process. PMID- 27405666 TI - X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene. AB - BACKGROUND: We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. RESULTS: We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8+ T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. CONCLUSION: Our observations establish a causal link between an ezrin radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency. PMID- 27405669 TI - Preventing bleeds by treatment: new era for haemophilia changing the paradigm. AB - INTRODUCTION: Coagulation products have allowed patients with severe haemophilia to lead a normal life. This is, however, only true for patients who received an early diagnosis and could start with primary prophylaxis. The absence of a positive family history for haemophilia, in the majority of children with severe haemophilia, postpones the age that treatment can be started. This makes general awareness of the clinical presentation important and a proper diagnosis a prerequisite for progress. The long delay between joint bleeding and overt arthropathy has been an important factor in the delay of implementation of primary prophylaxis. After the development of guidelines on 'how to treat', implementation of the advised practice is needed. Data collection of current treatment regimens in haemophilia centres will support the further optimization of the care for persons with haemophilia and further optimize treatment guidelines. Episodic ('on demand') therapy as a treatment strategy for severe haemophilia needs reconsideration. CONCLUSION: In an era where clotting factor concentrates are abundant and gene therapy a reality, all patients with severe haemophilia should be offered a strategy of bleeding prevention. PMID- 27405670 TI - Haemophilia treatment in 2030. AB - INTRODUCTION: Looking into the future is difficult and sometimes hazardous. A reliable look into haemophilia treatment in 2030 should be based on history and contemporary progress as well as dilemmas. Today, the issue of inhibitors overshadows the entire haemophilia community together with lack of treatment for large parts of the world's persons with haemophilia. AIMS: The aim of this paper was to provide a perspective on haemophilia treatment in 2030 and its provenance. METHODS: Literature review on history, treatment of haemophilia today as well as of emerging therapies give a base for the author's opinion on haemophilia treatment in 2030. RESULTS: Development of haemophilia treatment has virtually exploded during the last decade and a number of new clotting factor concentrates and alternative approaches are in the pipeline. CONCLUSION: The collection of treatment resources that we can see on the horizon gives hope that each person with haemophilia will get the care needed in 2030. The products used will be directed by individual needs and tailored to regional and local situations. PMID- 27405671 TI - Genomics of platelet disorders. AB - Genetic diagnosis in families with inherited platelet disorders (IPD) is not performed widely because of the genetic heterogeneity of this group of disorders and because in most cases, it is not possible to select single candidate genes for analysis using clinical and laboratory phenotypes. Next-generation sequencing (NGS) technology has revolutionized the scale and cost-effectiveness of genetic testing, and has emerged as a valuable tool for IPD. This review examines the potential utility of NGS as a diagnostic tool to streamline detection of causal variants in known IPD genes and as a vehicle for new gene discovery. PMID- 27405672 TI - Extended half-life clotting factor concentrates: results from published clinical trials. AB - Extended half-life clotting factor concentrates have been recently introduced into the armamentarium of treatments for patients with haemophilia A and B. In general, the data from published studies have demonstrated these products to be safe with no inhibitors reported in previously treated patients and efficacious with the advantage of a longer half-life allowing for less frequent intravenous infusions of factor. This enhanced convenience has led to some patients not previously on prophylaxis to begin prophylaxis while for others, especially children, has led to the ability to provide prophylaxis with reduced use of central venous catheters. The extended half-life factor IX products are now allowing patients to dose every 1-2 weeks while maintaining higher trough levels while the extended half-life factor VIII products have reduced the frequency of administration for patients on prophylaxis to as infrequent as once per week for some patients and to twice per week for all patients including younger children. It is important to note that data from previously untreated patients have not been published yet and the incidence for inhibitors in this patient population is as of yet unknown. The era of extended half-life clotting factor products has begun and the challenge for the haemophilia community will be how to best integrate these products into haemophilia clinical practice. PMID- 27405673 TI - Innovating immune tolerance induction for haemophilia. AB - INTRODUCTION: Haemophilia A is an X-linked bleeding disorder characterized by a deficiency of coagulation protein factor VIII (FVIII). A challenging complication of therapeutic FVIII infusions is the formation of neutralizing alloantibodies against the FVIII protein defined as inhibitors. The development of FVIII inhibitors drastically alters the quality of life of the patients and is associated with tremendous increases in morbidity as well as treatment costs. AIM: Current clinical immune tolerance induction protocols to reverse inhibitors are lengthy, costly and not effective in all patients. Prophylactic protocols to prevent inhibitor formation have not yet been developed in the clinical setting. However, there has been ample progress towards this goal in recent years in preclinical studies using animal models of haemophilia. METHODS: Here, we review the mechanisms that lead to inhibitor formation against FVIII and two promising new strategies for antigen-specific tolerance induction. RESULTS: CD4+ T cells play an important role in the FVIII-specific B cell response. Immune tolerance can be induced based on transplacental delivery of FVIII domains fused to Fc or on oral delivery of leaf cells from chloroplast transgenic crop plants. CONCLUSIONS: Recent literature suggests that prophylactic tolerance induction protocols for FVIII may be feasible in haemophilia A patients. PMID- 27405674 TI - Alternative therapies for the management of inhibitors. AB - The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains a major treatment complication encountered in the treatment of haemophilia. Not all patients with even the same severity and genotype develop inhibitors suggesting an underlying mechanism of tolerance against FVIII- or FIX-related immunity. One mechanism may be central tolerance observed in patients in whom the FVIII mutation enables some production of the protein. The other is a peripheral tolerance mechanism which may be evident in patients with null mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI-1, BAX801) has been developed for the haemostatic treatment of both congenital haemophilia with inhibitor (CHAWI) and acquired haemophilia A (AHA). In 28 subjects with AHA with life-/limb-threatening bleeding, rpFVIII reduced or stopped bleeding in all patients within 24 h. The cross-reactivity of anti-human FVIII antibodies to rpFVIII remains around 30-50%. Recently, new therapeutics based on the quite novel concepts have been developed and clinical studies are ongoing. These are humanized asymmetric antibody mimicking FVIIIa function by maintaining a suitable interaction between FIXa and FX (Emicizumab, ACE910), and small interfering RNAs (siRNA, ALN-AT3) suppress liver production of AT through post-transcriptional gene silencing and a humanized anti-TFPI monoclonal antibody (Concizumab). Their main advantages are longer half-life, subcutaneous applicability and efficacy irrespective of the presence of inhibitors which will make it easier to initiate more effective treatment especially early childhood. PMID- 27405675 TI - Genomic approaches to bleeding disorders. AB - The genes encoding the coagulation factors were characterized over two decades ago. Since then, significant progress has been made in the genetic diagnosis of the two commonest severe inherited bleeding disorders, haemophilia A and B. Experience with the genetic of inherited rare bleeding disorders and platelet disorders is less well advanced. Rare bleeding disorders are usually inherited as autosomal recessive disorders, while it is now clear that a number of the more common platelet function disorders are inherited as autosomal dominant traits. In both cases, DNA sequencing has been useful since most of these disorders are due to mutations located at the coding regions or splice sites of genes encoding the abnormal protein. However, in 5-10% of patients affected with severe clotting factor deficiencies, no genetic defect can be identified and until recently, the genetic characterization of inherited platelet disorders had been confined to the more prevalent conditions such as Glanzmann disease and Bernard-Soulier syndrome. In patients with no gene mutations identified, so far, the role of next generation sequencing as well as of other new genomic technologies will very likely have increasing importance. However, such methods require extensive bioinformatics analysis that, in turn will require critical revision of our current diagnostic infrastructure. PMID- 27405676 TI - Medical co-morbidities of patients with haemophilia: pain, obesity and hepatitis C. AB - Clinical care of patients with haemophilia (PWH) has progressed rapidly over the past decade. Current therapy has allowed patients with haemophilia to live longer and many patients are now experiencing the co-morbidities of the general population. In this review article, we focus on three common diseases states that affect PWH: chronic pain, obesity and hepatitis C. Pain has been a co-morbidity for many years and PWH often have unusual needs for chronic pain relief compared to the general population. Obesity is not only increasing in the general population but also in patients with hereditary bleeding disorders. The co morbidity of obesity not only causes increased pain progression and joint damage but also affects the dosing of factor concentrates. Finally, hepatitis C is known to have infected the majority of patients who received non-virally inactivated pooled factor concentrates in the past. New treatment regimens have been developed that allow the nearly uniform cure of chronic hepatitis C with a short course of oral medications. PMID- 27405677 TI - State of the art: von Willebrand disease. AB - The State of the Art in von Willebrand disease (VWD) has been impacted not only by discoveries in the field of haemostasis, but also by changes in practice in other fields. The development of bleeding assessment tools has led to the clarification of bleeding symptoms and phenotype in VWD. New discoveries in the biology and genetics of von Willebrand factor (VWF) are challenging our existing diagnostics and classification(s). An improved understanding of reproductive physiology and the pathology of VWD along with changing obstetric, gynaecologic and haemostatic therapies necessitate an evolving response to the care of women with VWD. The survival of patients with autoimmune disease, malignancies and congenital heart disease along with increasing use of circulatory support devices and extracorporeal membrane oxygenation is increasing the prevalence of acquired von Willebrand syndrome. In each of these challenges, there are opportunities to improve the care of our patients with VWD. PMID- 27405678 TI - Rare coagulation disorders: fibrinogen, factor VII and factor XIII. AB - Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. PMID- 27405679 TI - State of the art: gene therapy of haemophilia. AB - Clinical gene therapy has been practiced for more than a quarter century and the first products are finally gaining regulatory/marketing approval. As of 2016, there have been 11 haemophilia gene therapy clinical trials of which six are currently open. Each of the ongoing phase 1/2 trials is testing a variation of a liver-directed adeno-associated viral (AAV) vector encoding either factor VIII (FVIII) or factor IX (FIX) . As summarized herein, the clinical results to date have been mixed with some perceived success and a clear recognition of the immune response to AAV as an obstacle to therapeutic success. We also attempt to highlight promising late-stage preclinical activities for AAV-FVIII where, due to inherent challenges with manufacture, delivery and transgene product biosynthesis, more technological development has been necessary to achieve results comparable to what has been observed previously for AAV-FIX. Finally, we describe the development of a stem cell-based lentiviral vector gene therapy product that has the potential to provide lifelong production of FVIII and provide a functional 'cure' for haemophilia A. Integral to this program has been the incorporation of a blood cell-specific gene expression element driving the production of a bioengineered FVIII designed for optimal efficiency. As clearly outlined herein, haemophilia remains at the forefront of the rapidly advancing clinical gene therapy field where there exists a shared expectation that transformational advances are on the horizon. PMID- 27405680 TI - Recombinant to modified factor VIII and factor IX - chromogenic and one-stage assays issues. AB - The recent development of modified recombinant factor VIII (FVIII) and factor IX (FIX) therapeutic products with extended half-lives will create challenges for the haemostasis laboratory in obtaining recovery estimates of these products in clinical samples using existing assays. The new long-acting therapeutic concentrates contain molecular modifications of Fc fusion, site-specific of polyethylene glycol or albumin fusion. The optimum methods for monitoring each new product will need to be assessed individually and laboratories should select an assay which gives similar results to the assay used to assign potency to the product in question. For some extended half-life FVIII and FIX products some one stage assays are entirely unsuitable for monitoring purposes. For most products and assay reagents studied so far, and reviewed in this manuscript, chromogenic FVIII or FIX assays can be safely used with conventional plasma standards. If one stage assays are used then they should be performed using carefully selected reagents/methods which have been shown to recover activity close to the labelled potency for the specific product being monitored. PMID- 27405681 TI - Genetic analysis of bleeding disorders. AB - Molecular genetic analysis of inherited bleeding disorders has been practised for over 30 years. Technological changes have enabled advances, from analyses using extragenic linked markers to next-generation DNA sequencing and microarray analysis. Two approaches for genetic analysis are described, each suiting their environment. The Christian Medical Centre in Vellore, India, uses conformation sensitive gel electrophoresis mutation screening of multiplexed PCR products to identify candidate mutations, followed by Sanger sequencing confirmation of variants identified. Specific analyses for F8 intron 1 and 22 inversions are also undertaken. The MyLifeOurFuture US project between the American Thrombosis and Hemostasis Network, the National Hemophilia Foundation, Bloodworks Northwest and Biogen uses molecular inversion probes (MIP) to capture target exons, splice sites plus 5' and 3' sequences and to detect F8 intron 1 and 22 inversions. This allows screening for all F8 and F9 variants in one sequencing run of multiple samples (196 or 392). Sequence variants identified are subsequently confirmed by a diagnostic laboratory. After having identified variants in genes of interest through these processes, a systematic procedure determining their likely pathogenicity should be applied. Several scientific societies have prepared guidelines. Systematic analysis of the available evidence facilitates reproducible scoring of likely pathogenicity. Documentation of frequency in population databases of variant prevalence and in locus-specific mutation databases can provide initial information on likely pathogenicity. Whereas null mutations are often pathogenic, missense and splice site variants often require in silico analyses to predict likely pathogenicity and using an accepted suite of tools can help standardize their documentation. PMID- 27405682 TI - Quality laboratory issues in bleeding disorders. AB - Selected quality issues pertinent to the determination of accurate results in the haemostasis laboratory are discussed. Specifically, the implementation of a successful external quality-assessment scheme is described, including its impact on result accuracy as well as the programme's unique challenges and opportunities. Errors in the preanalytical phase of laboratory testing represent the greatest source for reporting incorrect test results. Some of the most common preanalytical errors are described including those that necessitate sample rejection. Analytical means to identify potential sources of error and analytical means to overcome particular interferences are described. Representing the most important clinical complication in the treatment of patients with haemophilia, quality issues related to determination of the presence of inhibitory antibodies against factor VIII (FVIII) are reviewed. Heat treatment of patient plasma prior to testing, particularly in patients receiving replacement FVIII concentrate or during induction of immune tolerance to achieve more accurate results is recommended, while screening activated partial thromboplastin time-based mixing tests to rule out inhibitor presence is discouraged. The initiatives presented in this review can be implemented in robust and resource restricted settings to improve the quality of laboratory testing in patients with bleeding disorders. PMID- 27405683 TI - Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders. AB - Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described. PMID- 27405684 TI - Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non-Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405). AB - Based on our preclinical study results, which showed that the activation of the hepatocyte growth factor/MET pathway is a potential mechanism of acquired resistance to alectinib, we launched the ALRIGHT (OLCSG1405 [alectinib-refractory non-small-cell lung cancer patients harboring the EML4-ALK fusion gene]), a phase II trial of the anaplastic lymphoma kinase (ALK)/MET inhibitor crizotinib in patients with non-small-cell lung cancer refractory to alectinib and harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is set as the objective response rate, assuming that a response in 50% of eligible patients will indicate potential usefulness and that 15% would be the lower limit of interest (1-sided alpha of 0.05, beta of 0.20). The estimated accrual number of patients is 9. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We will also take tissue samples before crizotinib monotherapy to conduct an exploratory analysis of ALK and hepatocyte growth factor/MET expression levels and gene alterations (eg, mutations, amplifications, and translocations). We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK+ non-small-cell lung cancer even in the alectinib-refractory setting. PMID- 27405685 TI - Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone. AB - OBJECTIVES: The release of magnesium ions (Mg2+ ) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. METHODS: Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. RESULTS: Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. SIGNIFICANCE: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2118-2125, 2017. PMID- 27405686 TI - Behavioral adaptations imply a direct link between ecological specialization and reproductive isolation in a sympatrically diverging ground beetle. AB - Adaptation to a previously unoccupied niche within a single population is one of the most contentious topics in evolutionary biology as it assumes the simultaneous evolution of ecologically selected and preference traits. Here, we demonstrate behavioral adaptation to contrasting hydrological regimes in a sympatric mosaic of Pogonus chalceus beetle populations, and argue that this adaptation may result in nonrandom gene flow. When exposed to experimental inundations, individuals from tidal marshes, which are naturally subjected to frequent but short floods, showed a higher propensity to remain submerged compared to individuals from seasonal marshes that are inundated for several months. This adaptive behavior is expected to decrease the probability that individuals will settle in the alternative habitat, resulting in spatial sorting and reproductive isolation of both ecotypes. Additionally, we show that this difference in behavior is induced by the environmental conditions experienced by the beetles during their nondispersive larval stages. Hence, accidental or forced ovipositioning in the alternative habitat may induce both an increased performance and preference to the natal habitat type. Such plastic traits could play an important role in the most incipient stages of divergence with gene flow. PMID- 27405687 TI - 3D Geometric Analysis of the Pediatric Aorta in 3D MRA Follow-Up Images with Application to Aortic Coarctation. AB - BACKGROUND: Coarctation of the aorta is one of the most common congenital heart diseases. Despite different treatment opportunities, long-term outcome after surgical or interventional therapy is diverse. Serial morphologic follow-up of vessel growth is necessary, because vessel growth cannot be predicted by primer morphology or a therapeutic option. OBJECTIVES: For the analysis of the long-term outcome after therapy of congenital diseases such as aortic coarctation, accurate 3D geometric analysis of the aorta from follow-up 3D medical image data such as magnetic resonance angiography (MRA) is important. However, for an objective, fast, and accurate 3D geometric analysis, an automatic approach for 3D segmentation and quantification of the aorta from pediatric images is required. METHODS: We introduce a new model-based approach for the segmentation of the thoracic aorta and its main branches from follow-up pediatric 3D MRA image data. For robust segmentation of vessels even in difficult cases (e.g., neighboring structures), we propose a new extended parametric cylinder model that requires only relatively few model parameters. Moreover, we include a novel adaptive background-masking scheme used for least-squares model fitting, we use a spatial normalization scheme to align the segmentation results from follow-up examinations, and we determine relevant 3D geometric parameters of the aortic arch. RESULTS: We have evaluated our proposed approach using different 3D synthetic images. Moreover, we have successfully applied the approach to follow up pediatric 3D MRA image data, we have normalized the 3D segmentation results of follow-up images of individual patients, and we have combined the results of all patients. We also present a quantitative evaluation of our approach for four follow-up 3D MRA images of a patient, which confirms that our approach yields accurate 3D segmentation results. An experimental comparison with two previous approaches demonstrates that our approach yields superior results. CONCLUSIONS: From the results, we found that our approach is well suited for the quantification of the 3D geometry of the aortic arch from follow-up pediatric 3D MRA image data. In future work, this will enable to investigate the long-term outcome of different surgical and interventional therapies for aortic coarctation. PMID- 27405688 TI - The impact of maternal- and neonatal-associated factors on human milk's macronutrients and energy. AB - OBJECTIVES: To test the impact of specific maternal- and neonatal-associated factors on human milk's macronutrients and energy. METHODS: This study was conducted with the use of a human milk analyzer (HMA, MIRIS, Uppsala, Sweden). Six hundred and thirty samples of raw milk and 95 samples of donor pasteurized milk were delivered from a total of 305 mothers. RESULTS: A significant inverse correlation of fat, protein and energy content with gestational age and birth weight was established. Fat and energy were lower in colostrum, increased in transitional milk and decreased on the 30th day's mature milk compared to transitional. The rate of protein decline from colostrum to mature milk was lower in premature deliveries compared to that of full-terms, resulting in greater contents of protein in preterm mature milk. The upmost amounts of carbohydrates were found in mature milk of preterm deliveries. A positive correlation was found between maternal age and fat contents. In women with higher post-pregnancy BMI levels greater analogies of fat and energy were presented. In women suffering diet-controlled gestational diabetes (GD), lower protein and higher fat and energy levels were found. CONCLUSIONS: Prematurity, maternal age, diet-controlled GD and high post-pregnancy BMI levels were found to impose statistical significant effect on milk's macronutrients and energy. PMID- 27405689 TI - Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening. AB - Structure-based virtual screening of two libraries containing 567 981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 MUM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series. PMID- 27405690 TI - Disentangling adaptive evolutionary radiations and the role of diet in promoting diversification on islands. AB - Although the initial formulation of modern concepts of adaptive radiation arose from consideration of the fossil data, rigorous attempts to identify this phenomenon in the fossil record are largely uncommon. Here I focus on direct evidence of the diet (through tooth-wear patterns) and ecologically-relevant traits of one of the most renowned fossil vertebrates-the Miocene ruminant Hoplitomeryx from the island of Gargano-to deepen our understanding of the most likely causal forces under which adaptive radiations emerge on islands. Results show how accelerated accumulation of species and early-bursts of ecological diversification occur after invading an island, and provide insights on the interplay between diet and demographic (population-density), ecological (competition/food requirements) and abiotic (climate-instability) factors, identified as drivers of adaptive diversification. A pronounced event of overpopulation and a phase of aridity determined most of the rate and magnitude of radiation, and pushed species to expand diets from soft-leafy foods to tougher harder items. Unexpectedly, results show that herbivorous mammals are restricted to browsing habits on small-islands, even if bursts of ecological diversification and dietary divergence occur. This study deepens our understanding of the mechanisms promoting adaptive radiations, and forces us to reevaluate the role of diet in the origins and evolution of islands mammals. PMID- 27405691 TI - Pseudoaneurysm of the mitral-aortic intervalvular fibrosa nine years after aortic valve replacement. PMID- 27405692 TI - Hounsfield unit recovery in clinical cone beam CT images of the thorax acquired for image guided radiation therapy. AB - A comprehensive artefact correction method for clinical cone beam CT (CBCT) images acquired for image guided radiation therapy (IGRT) on a commercial system is presented. The method is demonstrated to reduce artefacts and recover CT-like Hounsfield units (HU) in reconstructed CBCT images of five lung cancer patients. Projection image based artefact corrections of image lag, detector scatter, body scatter and beam hardening are described and applied to CBCT images of five lung cancer patients. Image quality is evaluated through visual appearance of the reconstructed images, HU-correspondence with the planning CT images, and total volume HU error. Artefacts are reduced and CT-like HUs are recovered in the artefact corrected CBCT images. Visual inspection confirms that artefacts are indeed suppressed by the proposed method, and the HU root mean square difference between reconstructed CBCTs and the reference CT images are reduced by 31% when using the artefact corrections compared to the standard clinical CBCT reconstruction. A versatile artefact correction method for clinical CBCT images acquired for IGRT has been developed. HU values are recovered in the corrected CBCT images. The proposed method relies on post processing of clinical projection images, and does not require patient specific optimisation. It is thus a powerful tool for image quality improvement of large numbers of CBCT images. PMID- 27405693 TI - Management of the Chronic Leukemias: Special Considerations in the Elderly Patient. Part II: Chronic Granulocytic Leukemia. PMID- 27405694 TI - Successful Cytoreduction with CAG (cytarabine, Aclarubicin and G-CSF) Therapy in Refractory Acute Myelogenous Leukemia before Allogeneic Stem Cell Transplantation. AB - Refractory acute myelogenous leukemia (AML) has a poor prognosis, and a long-term survival cannot be expected in most patients even if allogeneic bone marrow transplantation (allo-BMT) or allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is performed. An abundance of residual leukemic cells and poor performance status of patients before allo-BMT are often associated with a high relapse rate and high transplant-related mortality. Thus, to improve the prognosis of patients with refractory AML undergoing allo-BMT, it is necessary to reduce the leukemic cell volume as low as possible without severe complications. In this report, we used CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor (G-CSF)) therapy for cytoreduction before allo-BMT or allo-PBSCT in five patients with refractory AML. One of them achieved complete remission (CR) by CAG therapy alone and others achieved major tumor reduction prior to BMT and PBSCT. All patients achieved CR after allo-BMT and allo-PBSCT without severe complications. Three of them have remained CR for 9, 21 and 30 months, respectively. Although the results of this feasibility study are preliminary, the pre-transplant CAG therapy for refractory AML deserves further evaluation. PMID- 27405695 TI - A Case of Minimally Differentiated Acute Leukemia (AML-M0) Complicated by Ventricle Thrombosis During Remission-induction. AB - Sudden chest pain, dyspnea, and tachypnea occurred in a 21-year-old female who was undergoing induction chemotherapy under a diagnosis of minimally differentiated acute leukemia (M0). The arterial blood gas (ABG) tensions were decreased (PO2 71.6 mm Hg, PCO2 23.7 mm Hg), and an electrocardiogram showed a right-bundle branch block. Coagulation abnormalities (PT 73.1%, APTT 39.4 s, FDP 235mg/dl) were observed 72 h before onset. Echocardiography revealed a large thrombus in a right ventricle. A diagnosis of pulmonary thromboembolism (PTE) was made, and a tissue-type plasminogen activator (monteplase) was administered under percutaneous cardiopulmonary support (PCPS). The complete lysis of thrombus was confirmed by an echocardiogram 8 h later. Symptoms and ABG data were also improved. PTE in adult AML cases is rare, but should be considered as one of the life-threatening complications in AML patients under chemotherapy who develop respiratory difficulties. We suggest a careful monitoring of coagulation abnormalities for the prediction of PTE during chemotherapy for AML, and the use of tissue-type plasminogen activator (t-PA), monteplase, for the treatment of PTE in these cases. PMID- 27405696 TI - Short Communication: Expression of Apoptosis Regulating Factors on T Lymphocytes in Multiple Myeloma Patients. AB - Multiple myeloma (MM) is a malignant proliferation of plasma cells in which dysregulation of programmed cell death (apoptosis) is responsible for tumor cell expansion. However some phenotypic and functional alterations of T cells in MM patients have been reported, that also can influence the plasma cell growth. The aim of the study was to assess some aspects of T lymphocyte apoptosis in MM to obtain a better understanding of the changes in the immune system in this disease. Flow cytometry was used to analyze the expression of two main regulators of apoptosis: the pro-apoptotic Fas antigen and the anti-apoptotic protein BCL-2 in patients with untreated MM and in healthy controls. ELISA was used to determine soluble Fas ligand (sFasL) serum levels in patients and control groups. We detected statistically significant higher Fas expression in patients than in controls both on CD4 and CD8 lymphocytes, but no differences in BCL-2 expression by these cells. The sFasL level was statistically significant lower in patients than in controls. Our results indicate that T cells in MM are controlled by up regulation of Fas. The Fas/FasL system induces the killing of T cells expressing Fas antigen, what could account for the incapability of the immune system to protect host against tumor expansion. PMID- 27405697 TI - Hereditary Red Cell Membrane Disorders in Japan: Their Genotypic and Phenotypic Features in 1014 Cases Studied. AB - This study describes the characteristic features of the incidence of hereditary red cell membrane disorders in the Japanese population based on studies of 1014 cases of these disorders from 605 kindred. Among them, there were 581 cases of hereditary spherocytosis (HS) from 303 kindred, 137 cases of hereditary elliptocytosis (HE) from 68 kindred, 104 cases of hereditary stomatocytosis (HSt) from 64 kindred, and 34 cases of protein 4.2 (P4.2) anomalies from 20 kindred, and 41 cases of membrane lipid anomalies from 27 kindred. In HS patients, eleven mutations of the band 3 (B3) gene, 15 mutations of the ankyrin gene, and three mutations of the protein 4.2 (P4.2) gene, which are pathognomonic for this disorder, were identified. Most of these mutations had not been reported and, with few exceptions, were specific to the Japanese population. P4.2 abnormalities also appear to be unique to the Japanese population. The biochemical and biophysical functions of P4.2 are associated with stabilization of the cytoskeletal network by anchoring it to integral proteins (especially B3). Biochemical and genetic analyses of the HE patients revealed one family with an alpha-spectrin (Sp) anomaly (HE [alpha(1/74)]) and three kindred with beta spectrin abnormalities (beta-Sp Yamagata, beta-Sp Tokyo, and beta-Sp Nagoya) due to abnormal splicings of the beta-Sp gene. On the basis of these observations, the relationship between the genotypes and phenotypes is reviewed. In addition, the morphogenesis of red cell membranes with regard to the sequential expression of these membrane proteins was also discussed. Finally, from the standpoint of gene expression, a possible role of gene methylation as an epigenetic control was proposed. PMID- 27405698 TI - Detection and Identification of Single Molecules in Immunology and Immunohematology: Single (solution)-phase Single-molecule FCS. AB - In the Goodpasture experiment, we determined a probability of 99.1% of identifying one single immune complex. Under these conditions, a single molecule event is proven. There exist no instrumental assumptions of our approach on which the experiments themselves, the theoretical background or the conclusion are based on. Our results open up a broad field for analytics and diagnostics in solution, particularly in immunology and immunohematology. PMID- 27405699 TI - Are there "Attenuated" Forms of Evans Syndrome? AB - Indirect evidence of hemolysis has been described in patients with autoimmune thrombocytopenic purpura. In order to collect more data, another method to assess red blood cell destruction in these patients was employed: measurement of free haptoglobin levels. In 17 individuals with autoimmune thrombocytopenic purpura the levels of free haptoglobins were assessed after carefully ruling out microangiopathic hemolysis, systemic lupus erythematosus or overt Evans syndrome. Abnormally low levels of free haptoglobins were found in five individuals (29%) as indirect evidence of hemolysis. The long-term thrombocytopenia-free status was lower in patients with low haptoglobin levels than in those with normal levels (40 versus 58%). These data, added to previous evidence, support the observation of Evans made 50 years ago: "there is a spectrum-like relationship between primary thrombocytopenia and haemolytic anemia".". Accordingly, the concept of "attenuated" variants of the Evans syndrome could be entertained. PMID- 27405700 TI - Is Granulocyte Colony-stimulating Factor Safe in the Treatment of Febrile Neutropenia in Lymphoma Patients with Renal Transplantation? PMID- 27405702 TI - Interpregnancy interval after live birth or pregnancy termination and estimated risk of preterm birth: a retrospective cohort study. AB - OBJECTIVES: We assessed whether interpregnancy interval (IPI) length after live birth and after pregnancy termination was associated with preterm birth (PTB). DESIGN: Multiyear birth cohort. SETTINGS: Fetal death, birth and infant death certificates in California merged with Office of Statewide Health Planning and Development. POPULATION: One million California live births (2007-10) after live birth and after pregnancy termination. METHODS: Logistic regression was used to estimate odds ratios (ORs) of PTB of 20-36 weeks of gestation and its subcategories for IPIs after a live birth and after a pregnancy termination. We used conditional logistic regression (two IPIs/mother) to investigate associations within mothers. MAIN OUTCOME MEASURE: PTB relative to gestations of >= 37 weeks. RESULTS: Analyses included 971 211 women with IPI after live birth, and 138 405 women with IPI after pregnancy termination with 30.6% and 74.6% having intervals of <18 months, respectively. IPIs of <6 months or 6-11 months after live birth showed increased odds of PTB adjusted ORs for PTB of 1.71 (95% CI 1.65-1.78) and 1.20 (95% CI 1.16-1.24), respectively compared with intervals of 18-23 months. An IPI >36 months (versus 18-23 months) was associated with increased odds for PTB. Short IPI after pregnancy termination showed a decreased OR of 0.87 (95% CI 0.81-0.94). The within-mother analysis showed the association of increased odds of PTB for short IPI, but not for long IPI. CONCLUSIONS: Women with IPI <1 or >3 years after a live birth were at increased odds of PTB-an important group for intervention to reduce PTB. Short IPI after pregnancy termination was associated with reduced odds for PTB and needs to be further explored. TWEETABLE ABSTRACT: Short and long IPI after live birth, but not after pregnancy termination, showed increased odds for PTB. PMID- 27405705 TI - Reverse solvatochromism in solvent binary mixtures: a case study using a 4 (nitrostyryl)phenolate as a probe. AB - A 4-(nitrostyryl)phenolate was synthesized and its use in pure solvents revealed a reversion in solvatochromism. Solutions of a dye in binary solvent mixtures, using as components the solvents in the region of the occurrence of the reversion, provided the first case in the literature of reverse solvatochromism in a binary mixture. PMID- 27405703 TI - Quantification of liver fat in the presence of iron overload. AB - PURPOSE: To evaluate the accuracy of R2* models (1/T2 * = R2*) for chemical shift encoded magnetic resonance imaging (CSE-MRI)-based proton density fat-fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard. MATERIALS AND METHODS: Two Monte Carlo simulations were implemented to compare the root-mean-squared-error (RMSE) performance of single-R2* and dual-R2* correction in a theoretical liver environment with high iron. Fatty liver was defined as hepatic PDFF >5.6% based on MRS; only subjects with fatty liver were considered for analyses involving fat. From a group of 40 patients with known/suspected iron overload, nine patients were identified at 1.5T, and 13 at 3.0T with fatty liver. MRS linewidth measurements were used to estimate R2* values for water and fat peaks. PDFF was measured from CSE-MRI data using single-R2* and dual-R2* correction with magnitude and complex fitting. RESULTS: Spectroscopy-based R2* analysis demonstrated that the R2* of water and fat remain close in value, both increasing as iron overload increases: linear regression between R2*W and R2*F resulted in slope = 0.95 [0.79-1.12] (95% limits of agreement) at 1.5T and slope = 0.76 [0.49 1.03] at 3.0T. MRI-PDFF using dual-R2* correction had severe artifacts. MRI-PDFF using single-R2* correction had good agreement with MRS-PDFF: Bland-Altman analysis resulted in -0.7% (bias) +/- 2.9% (95% limits of agreement) for magnitude-fit and -1.3% +/- 4.3% for complex-fit at 1.5T, and -1.5% +/- 8.4% for magnitude-fit and -2.2% +/- 9.6% for complex-fit at 3.0T. CONCLUSION: Single-R2* modeling enables accurate PDFF quantification, even in patients with iron overload. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:428-439. PMID- 27405704 TI - The effect of communicating the genetic risk of cardiometabolic disorders on motivation and actual engagement in preventative lifestyle modification and clinical outcome: a systematic review and meta-analysis of randomised controlled trials. AB - Genetic risk prediction of chronic conditions including obesity, diabetes and CVD currently has limited predictive power but its potential to engage healthy behaviour change has been of immense research interest. We aimed to understand whether the latter is indeed true by conducting a systematic review and meta analysis investigating whether genetic risk communication affects motivation and actual behaviour change towards preventative lifestyle modification. We included all randomised controlled trials (RCT) since 2003 investigating the impact of genetic risk communication on health behaviour to prevent cardiometabolic disease, without restrictions on age, duration of intervention or language. We conducted random-effects meta-analyses for perceived motivation for behaviour change and clinical changes (weight loss) and a narrative analysis for other outcomes. Within the thirteen studies reviewed, five were vignette studies (hypothetical RCT) and seven were clinical RCT. There was no consistent effect of genetic risk on actual motivation for weight loss, perceived motivation for dietary change (control v. genetic risk group standardised mean difference (smd) 0.15; 95 % CI -1.03, 0.73, P=0.74) or actual change in dietary behaviour. Similar results were observed for actual weight loss (control v. high genetic risk SMD 0.29 kg; 95 % CI -0.74, 1.31, P=0.58). This review found no clear or consistent evidence that genetic risk communication alone either raises motivation or translates into actual change in dietary intake or physical activity to reduce the risk of cardiometabolic disorders in adults. Of thirteen studies, eight were at high or unclear risk of bias. Additional larger-scale, high-quality clinical RCT are warranted. PMID- 27405706 TI - Codeine versus placebo for chronic cough in children. AB - BACKGROUND: Cough in children is a commonly experienced symptom that is associated with increased health service utilisation and burden to parents. The presence of chronic (equal to or more than four weeks) cough in children may indicate a serious underlying condition such as inhaled foreign body or bronchiectasis. Codeine (and derivative)-based medications are sometimes used to treat cough due to their antitussive properties. However, there are inherent risks associated with the use of these medications such as respiratory drive suppression, anaesthetic-induced anaphylaxis, and addiction. Metabolic response and dosage variability place children at increased risk of experiencing such side effects. A systematic review evaluating the quality of the available literature would be useful to inform management practices. OBJECTIVES: To evaluate the safety and efficacy of codeine (and derivatives) in the treatment of chronic cough in children. SEARCH METHODS: We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to 8 June 2016), EMBASE (1974 to 8 June 2016), the online trials registries of the World Health Organization and ClinicalTrials.gov, and the bibliographic references of publications. We imposed no language restrictions. SELECTION CRITERIA: We considered studies eligible for analysis when: the participant population included children aged less than 18 years with chronic cough (duration equal to or more than four weeks at the time of intervention); and the study design evaluated codeine or codeine-based derivatives against placebo through a randomised controlled trial. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results to determine eligibility against a standardised criteria, and we had a pre-planned method for analysis. MAIN RESULTS: We identified a total of 556 records, of which 486 records were excluded on the basis of title and abstract. We retrieved the remaining 70 references in full to determine eligibility. No studies fulfilled the inclusion criteria of this review, and thus we found no evidence to support or oppose the use of codeine or derivatives as antitussive agents for chronic cough in children.While chronic cough is not the same as acute cough, systematic reviews on the use of codeine efficacy for acute cough in children conclude an overall lack of evidence to support or oppose the use of over-the-counter cough and cold medications containing codeine (or derivatives) for treatment of acute cough in children. The lack of sufficient evidence to support the use of these medications has been consistently reaffirmed by medical experts in international chronic cough guidelines and by governing medical and pharmaceutical authorities in the USA, Europe, Canada, New Zealand, and Australia. Due to the lack of sufficient evidence to support efficacy, and the known risks associated with use - in particular the increased risks for children - these medications are now not recommended for children less than 12 years of age and children between 12 to 18 years with respiratory conditions. AUTHORS' CONCLUSIONS: This review has highlighted the absence of any randomised controlled trials evaluating codeine based medications in the treatment of childhood chronic cough. Given the potential adverse events of respiratory suppression and opioid toxicity, national therapeutic regulatory authorities recommend the contraindication of access to codeine in children less than 12 years of age. We suggest that clinical practice adhere to clinical practice guidelines and thus refrain from using codeine or its derivatives to treat cough in children. Aetiological-based management practices continue to be advocated for children with chronic cough. PMID- 27405708 TI - Nutrition and infectious disease. PMID- 27405709 TI - Glucose-6-phosphate dehydrogenase deficiency: a new hypothesis for an old disease. PMID- 27405707 TI - Receptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells. AB - Neuronal transmission is regulated by the local circuitry which is composed of principal neurons targeted at different subcellular compartments by a variety of interneurons. However, mechanisms that contribute to the subcellular localisation and maintenance of GABAergic interneuron terminals are poorly understood. Stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin and its interaction with the guanine nucleotide exchange factor collybistin. Lentiviral knockdown experiments in adult rats indicated that the receptor tyrosine kinase EphA7 is required for the stabilisation of basket cell terminals on proximal dendritic and somatic compartments of granular cells of the dentate gyrus. EphA7 deficiency and concomitant destabilisation of GABAergic synapses correlated with impaired long term potentiation and reduced hippocampal learning. Reduced GABAergic innervation may be explained by an impact of EphA7 on gephyrin clustering. Overexpression or ephrin stimulation of EphA7 induced gephyrin clustering dependent on the mechanistic target of rapamycin (mTOR) which is an interaction partner of gephyrin. Gephyrin interactions with mTOR become released after mTOR activation while enhanced interaction with the guanine nucleotide exchange factor collybistin was observed in parallel. In conclusion, EphA7 regulates gephyrin clustering and the maintenance of inhibitory synaptic connectivity via mTOR signalling. PMID- 27405710 TI - Vitamin E and neurological function: lessons from patients with abetalipoproteinaemia. AB - For many years the role of vitamin E (alpha-tocopherol) in human nutrition was uncertain, but it is now recognised that this fat soluble vitamin is necessary for normal neurological structure and function. The evidence came initially from patients with abetalipoproteinaemia, then from patients with other chronic and severe fat malabsorptive states, from patients with an isolated deficiency of vitamin E without generalised fat malabsorption, and from comparative neuropathological studies in vitamin E deficient man, monkey and rat. Severe and chronic vitamin E deficiency in the different patient groups resulted in a characteristic neurological disorder which progressed to crippling and blindness. Early and appropriate supplementation with vitamin E can prevent the development of all the neurological signs and symptoms, and treatment of patients with established lesions invariably halts and in some cases can reverse the neuropathy. These clinical and pathological findings raise a number of basic questions regarding the function of vitamin E in neural tissues which are currently being addressed in an animal model. PMID- 27405711 TI - Assay of phagocyte activation by means of malondialdehyde and luminol-enhanced chemiluminescence during uneventful wound healing following trauma surgery. AB - The purpose of the study was the assessment of the acute inflammatory response in patients (N = 12) with comparable trauma severity and uneventful wound healing courses in the postsurgical period as a contribution to the search for objectifiable criteria in the monitoring of wound healing. Whole blood chemiluminescence (CL) on the one hand and the lipid peroxidation product malondialdehyde (MDA) on the other hand as tools for the detection of the respiratory burst activity of phagocytes were used as inflammation markers and were compared with the established marker PMN elastase. Blood samples were withdrawn daily from the day of surgery to the 14th postsurgical day. CL parameters and PMN elastase increased postoperatively reflecting surgical trauma, while MDA remained within the normal range during the whole time of observation. A decrease of CL-activity in the postsurgical period correlated with decreasing PMN elastase levels (r = 0.52, P<0.0001) as well as with the tapering of local inflammation signs concerning the wound situs. MDA values neither correlated with PMN elastase nor with any CL-parameters. The results indicate that the measurement of the phagocytic activation by CL, used for the first time in traumatology to monitor wound healing, represents a promising marker for the assessment of the actual inflammatory status. PMID- 27405712 TI - Activities of free radical and DNA turn-over enzymes in cancerous and non cancerous human brain tissues. AB - Activities of adenosine deaminase (ADA), 5' nucleotidase (5'NT), xanthine oxidase (XO), guanase (GUA), total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) enzymes were measured in cancerous brain tissues from 48 patients. The results were compared with those of the control brain tissues from 17 subjects. Important differences were found between enzyme activities of control brain tissues and those of tumoral tissues. There were important intracorrelations between some of the enzyme activities in both neoplastic and control brain tissues. The correlations exhibited significant differences between control group and patient groups, indicating disordered enzymatic relations in the cancerous brain tissues. The results suggest that enzymatic make-up relating to free radical and purine metabolism shows great differences between cancerous and non-cancerous brain tissues. Similar diversity is also present between various types of cancerous brain tissues. This implies that enzymatic make-up of the tissues also depends on the cancer type. We thus suggest that the results obtained from this kind of experimental studies should be evaluated individually for the tissue analyzed taking the cancer type into consideration without making general evaluations. PMID- 27405713 TI - Leishmanicidal activity of peroxynitrite. AB - Nitric oxide reacts with superoxide to produce peroxynitrite which has been reported to be highly microbicidal to Trypanosoma cruzi in phosphate buffer but ineffective against Leishmania major in culture medium. This contradiction and the potential importance of peroxynitrite as a cytotoxic effector molecule of both macrophages and neutrophils led us to re-examine its leishmanicidal effects. Our results demonstrate that peroxynitrite inhibits growth of Leishmania amazonensis promastigotes in a concentration-dependent manner both in phosphate buffer and culture medium (DMEM containing 20% fetal calf serum). In the latter, 43% growth inhibition was observed with 4 mM peroxynitrite whereas in buffer a 70% inhibition was already observed with 0.5 mM peroxynitrite. Treated parasites presented reduced motility and became round in shape further confirming the leishmanicidal activity of peroxynitrite. The latter was attenuated by reduced glutathione supporting the view that peroxynitrite-mediated oxidation of critical thiol groups is a major mechanism accounting for its trypanocidal activity. PMID- 27405714 TI - Lethal hydrogen peroxide toxicity involves lysosomal iron-catalyzed reactions with membrane damage. AB - Secondary lysosomes contain low-molecular weight iron-complexes as a consequence of normal autophagocytotic degradation of various metallo-proteins. Thus, entry of hydrogen peroxide into these organelles may induce ironcatalyzed oxidative reactions with ensuing damage to lysosomal membranes and leakage of destructive contents. The amount of lysosomal reactive iron and the cellular capacity to degrade hydrogen peroxide would then be important determining factors in cellular resistance to oxidative stress. The effects of hydrogen peroxide on cell viability and, in particular, on lysosomal membrane integrity, evaluated by acridine orange, lucifer yellow, neutral red, and cathepsin D relocalization, were investigated in a model system of cultured J-774 cells. The protective effect of the iron-chelator desferal was studied after exposure to the drug under ordinary culture conditions and after inhibition of cellular endocytosis. Hydrogen peroxide-exposure (500 MUM in PBS, 37 degrees C, 5-90 min) was manifested as a time-dependent decrease in cell viability. This was preceded by a rapid reduction of the proton gradient across the lysosomal membranes, as judged by relocalization of acridine orange. Another early sign of damage was plasma membrane blebbing, found on many cells within minutes after the initiation of hydrogen peroxide-exposure. The cells also showed a partial redistribution of the lysosomal markers lucifer yellow, neutral red, and cathepsin D, indicating lysosomal destabilization. The pre-exposure of cells to desferal in culture prevented all these phenomena, unless endocytotic uptake of the drug was prevented. PMID- 27405715 TI - Heme oxygenase-1 mRNA levels, metallothionein mRNA levels, lipid peroxidation and microsomal CYP1A activities in rats treated with 3,3-dichlorobenzidine and some other inducers of P450. AB - The effect of 3,3-dichlorobenzidine (DCB), a potent inducer of CYP1A, on the levels of heme oxygenase-1 mRNA and metallothionein mRNAs was examined in the kidney, liver and lung of rats administered a single ip dose (157 MUmol/kg) of the compound. DCB treatment increased heme oxygenase-I mRNA abundance in the kidney significantly from barely detectable levels in untreated animals; the maximum increase in the liver and lung was 24-fold and 4-fold, respectively. Hepatic microsomal heme oxygenase activity was also induced by DCB. In contrast with DCB, 2 other P450 inducers, beta-naphthoflavone (beta-NF) and phenobarbital did not elevate tissue HO-1 rnRNA levels. DCB pretreatment also elevated metallothionein mRNA levels in the kidney, liver and lung, with the effect in the lung being the least pronounced. In contrast with HO-1 mRNA, metallothionein mRNA was increased by the other P450 inducers examined. In vivo lipid peroxidation and in vitro NADPH-dependent microsomal lipid peroxidation were increased in the liver of DCB-treated rats but not in those of phenobarbital- or beta naphthoflavone-treated rats. Treatment with DCB or beta-NF did not alter total hepatic microsomal P450 content, as measured spectrophotometrically, but induced the activity of CYP1A2. In contrast, the activity of CYP1A1 was induced to a lesser extent by DCB than by beta-NF. The data show that DCB induces HO-1 as weD as P450 1A, confirm stimulation of lipid peroxidation by the compound, and suggest oxidative stress as a mechanism of HO-1 induction by the compound. PMID- 27405716 TI - Lipid peroxidation by peroxidase-catalyzed bioactivation of tyrosine. AB - Tyrosyl free radicals generated by the peroxidase-catalyzed oxidation of peptide tyrosyl residues are known to yield the stable cross-linked product dityrosine. In the present report, horseradish peroxidase is used as a model of peroxidase to study oxidative modifications of non-protein cellular components. Tyrosyl free radicals promote, as many free radicals, the decay of beta-phycoerythrin fluorescence emission, they oxidize NADH and ascorbic acid and initiate arachidonic acid peroxidation with formation of hydroperoxides and dienes. These results suggest that tyrosyl free radicals generated when tyrosine residues in protein and peptides are activated in vivo by peroxidase-H2O2 might undergo the peroxidation of membrane lipids. PMID- 27405717 TI - A sensitive fluorometric assay for protein-bound DOPA and related products of radical-mediated protein oxidation. AB - Oxidative attack on proteins results in the hydroxylation of tyrosyl residues to protein-bound DOPA (3,4-dihydroxyphenylalanine). Existing methods for assaying protein-bound DOPA have poor sensitivity and numerous possible interferences, such that accurate determination (especially of very low DOPA concentrations) has required time-consuming acid hydrolysis and HPLC analysis with fluorometric detection. This work presents a sensitive and selective assay for peptide or protein-bound o-benzoquinones derived from DOPA based on fluorometric detection of ethylenediamine derivatives. Detection limits for protein-bound DOPA are in tbe range 0.53-4.70 ng/mL for the assay mixture, corresponding to sample DOPA concentrations of 0.59-5.30 ng/mL (representing a minimum of 6-54 pmole detected), depending on the particular protein/peptide under study. The assay response increases linearly with DOPA concentration, and also with the extent of radical exposure of the protein. The assay is a simple and fast way to assess DOPA formation and thus oxidative damage in a protein. PMID- 27405718 TI - Lipid peroxidation: a novel enzymatic mechanism of protective effect of alpha tocopherol in biological membranes. PMID- 27405719 TI - Zinc inhibition of electron transfer: mechanism of beta receptor inhibition? AB - Zinc has been shown to inhibit beta-receptor activation of adenylate cyclase at a post receptor site. We have postulated that the beta-receptor is one of several receptors activated by reduction, followed by transmembrane elector transfer accelerated by GTP. GTP accelerates electron transfer in a model system and this accelerated electron transfer is inhibited by zinc. This could explain the mechanism of the post receptor inhibition by zinc of the adenylate cyclase stimulation which follows beta-receptor activation. PMID- 27405722 TI - Evidence of double layer/capacitive charging in carbon nanomaterial-based solid contact polymeric ion-selective electrodes. AB - This paper presents the first direct spectroscopic evidence for double layer or capacitive charging of carbon nanomaterial-based solid contacts in all-solid state polymeric ion-selective electrodes (ISEs). Here, we used synchrotron radiation-X-ray photoelectron spectroscopy (SR-XPS) and SR valence band (VB) spectroscopy in the elucidation of the charging mechanism of the SCs. PMID- 27405720 TI - TRAIP is involved in chromosome alignment and SAC regulation in mouse oocyte meiosis. AB - Recent whole-exome sequencing (WES) studies demonstrated that TRAIP is associated with primordial dwarfism. Although TRAIP was partially studied in mitosis, its function in oocyte meiosis remained unknown. In this study, we investigated the roles of TRAIP during mouse oocyte meiosis. TRAIP was stably expressed during oocytes meiosis and co-localized with CREST at the centromere region. Knockdown of TRAIP led to DNA damage, as revealed by the appearance of gammaH2AX. Although oocytes meiotic maturation was not affected, the proportions of misaligned chromosomes and aneuploidy were elevated after TRAIP knockdown, suggesting TRAIP is required for stable kinetochore-microtubule (K-MT) attachment. TRAIP knockdown decreased the accumulation of Mad2 on centromeres, potentially explaining why oocyte maturation was not affected following formation of DNA lesions. Securin, a protein which was prevent from precocious degradation by Mad2, was down-regulated after TRAIP knockdown. Inhibition of TRAIP by microinjection of antibody into pro metaphase I (pro-MI) stage oocytes resulted in precocious first polar body (PB1) extrusion, and live-cell imaging clearly revealed misaligned chromosomes after TRAIP knockdown. Taken together, these data indicate that TRAIP plays important roles in oocyte meiosis regulation. PMID- 27405721 TI - Targeting cellular mRNAs translation by CRISPR-Cas9. AB - Recently CRISPR-Cas9 system has been reported to be capable of targeting a viral RNA, and this phenomenon thus raises an interesting question of whether Cas9 can also influence translation of cellular mRNAs. Here, we show that both natural and catalytically dead Cas9 can repress mRNA translation of cellular genes, and that only the first 14 nt in the 5' end of sgRNA is essential for this process. CRISPR Cas9 can suppress the protein expression of an unintended target gene without affecting its DNA sequence and causes unexpected phenotypic changes. Using the designed RNA aptamer-ligand complexes which physically obstruct translation machinery, we indicate that roadblock mechanism is responsible for this phenomenon. Our work suggests that studies on Cas9 should avoid the potential off target effects by detecting the alteration of genes at both the DNA and protein levels. PMID- 27405723 TI - Development of an enhanced health-economic model and cost-effectiveness analysis of tiotropium + olodaterol Respimat(r) fixed-dose combination for chronic obstructive pulmonary disease patients in Italy. AB - BACKGROUND: The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat((r)) FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease. METHODS: While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual level Markov approach was selected for the new model. Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat((r)) FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage. Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT. Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data. Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included. A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service. RESULTS: Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat((r)) FDC with tiotropium alone, resulted in mean incremental costs per patient of ?1167 and an incremental cost-effectiveness ratio (ICER) of ?7518 per additional QALY with tiotropium + olodaterol Respimat((r)) FDC. The lung function outcomes observed for tiotropium + olodaterol Respimat((r)) FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium. Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat((r)) FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of ?20,000 and ?30,000 per QALY respectively. CONCLUSION: Tiotropium + olodaterol Respimat((r)) FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. PMID- 27405724 TI - Engineering Online and In-Person Social Networks for Physical Activity: A Randomized Trial. AB - BACKGROUND: Social networks can influence physical activity, but little is known about how best to engineer online and in-person social networks to increase activity. PURPOSE: The purpose of this study was to conduct a randomized trial based on the Social Networks for Activity Promotion model to assess the incremental contributions of different procedures for building social networks on objectively measured outcomes. METHODS: Physically inactive adults (n = 308, age, 50.3 (SD = 8.3) years, 38.3 % male, 83.4 % overweight/obese) were randomized to one of three groups. The Promotion group evaluated the effects of weekly emailed tips emphasizing social network interactions for walking (e.g., encouragement, informational support); the Activity group evaluated the incremental effect of adding an evidence-based online fitness walking intervention to the weekly tips; and the Social Networks group evaluated the additional incremental effect of providing access to an online networking site for walking as well as prompting walking/activity across diverse settings. The primary outcome was mean change in accelerometer-measured moderate-to-vigorous physical activity (MVPA), assessed at 3 and 9 months from baseline. RESULTS: Participants increased their MVPA by 21.0 min/week, 95 % CI [5.9, 36.1], p = .005, at 3 months, and this change was sustained at 9 months, with no between-group differences. CONCLUSIONS: Although the structure of procedures for targeting social networks varied across intervention groups, the functional effect of these procedures on physical activity was similar. Future research should evaluate if more powerful reinforcers improve the effects of social network interventions. TRIAL REGISTRATION NUMBER: The trial was registered with the ClinicalTrials.gov (NCT01142804). PMID- 27405725 TI - Identification of candidate genes for myeloma-induced osteocyte death based on microarray data. AB - BACKGROUND: The study was aimed to investigate the molecular mechanisms of osteocyte death in multiple myeloma (MM) patients. METHODS: GSE27372 was downloaded from Gene Expression Omnibus, including three HOB-01 (osteocyte cell line) control samples and three HOB-01 samples co-cultured with JJN3 (human MM cell line). After the differentially expressed genes (DEGs) were identified by Student's t test method, enrichment analyses were performed for them using DAVID software. Using TRANSFAC, TSGene, and tumor-associated gene (TAG) databases, functional annotation was conducted for the DEGs. Additionally, protein-protein interaction (PPI) network and sub-network analyses were performed using STRING database and Cytoscape software. RESULTS: Total 393 DEGs were identified, including 22 transcription factors (e.g., KLF4 and IRF8) and 37 TAGs. Enrichment analysis suggested that EGF, S1PR1, and NPY1R were enriched in the function of circulatory system development. EGF (degree = 31) and EGR1 (degree = 19) had high degrees and interactions in the PPI network. In the sub-network, S1PR1, C3AR1, and NPY1R could interact with each other. CONCLUSIONS: These DEGs might participate in the osteocyte apoptosis induced by myeloma cells. These findings might provide a theoretical basis for a better understanding of the osteolysis in MM patients. PMID- 27405726 TI - Network Analysis on Predicting Mean Diffusivity Change at Group Level in Temporal Lobe Epilepsy. AB - The two most common types of temporal lobe epilepsy are medial temporal sclerosis (TLE-MTS) epilepsy and MRI-normal temporal lobe epilepsy (TLE-no). TLE-MTS is specified by its stereotyped focus and spread pattern of neuronal damage, with pronounced neuronal loss in the hippocampus. TLE-no exhibits normal-appearing hippocampus and more widespread neuronal loss. In both cases, neuronal loss spread appears to be constrained by the white matter connections. Both varieties of epilepsy reveal pathological abnormalities in increased mean diffusivity (MD). We model MD distribution as a simple consequence of the propagation of neuronal damage. By applying this model on the structural brain connectivity network of healthy subjects, we can predict at group level the MD gray matter change in the epilepsy cohorts relative to a control group. Diffusion tensor imaging images were acquired from 10 patients with TLE-MTS, 11 patients with TLE-no, and 35 healthy subjects. Statistical validation at the group level suggests high correlation with measured neuronal loss (R = 0.56 for the TLE-MTS group and R = 0.364 for the TLE-no group). The results of this exploratory work pave the way for potential future clinical application of the proposed model on individual patients, including predicting neuronal loss spread, identification of seizure onset zones, and helping in surgical planning. PMID- 27405727 TI - Building a culture of health: A new framework and measures for health and health care in America. AB - For generations, Americans' health has been unequally influenced by income, education, ethnicity, and geography. Health care systems have operated largely apart from each other and from community life. The definition of health has been the "absence of illness," rather than the recognition that all aspects of our lives should support health. Today, a growing number of communities, regions, and states are working to redefine what it means to get and stay healthy by addressing the multiple determinants of health. The requirements of federal health care reform are changing who has access to care, how care is paid for and delivered, and how patients and providers interact. Coordinated efforts to promote wellness and prevent diseases are proliferating among a diverse set of stakeholders. These developments in health and in society present a window of opportunity for real societal transformation-a chance to catalyze a national movement that demands and supports a widely shared, multifaceted vision for a Culture of Health. To address this challenge, the Robert Wood Johnson Foundation has embarked on a strategic direction to use the tools of a large national philanthropy to catalyze a social movement which we are calling Building a Culture of Health. This article presents the Foundation's new model for a Culture of Health, the trans-disciplinary research that developed a set of metrics that tie to the model, and the community engagement activities undertaken in the development of both the model and metrics. The model and associated metrics and extensive communication, in addition to partnership, and grant funding strategies, represent a culture change strategy being implemented over 20 years. Addressing underlying inequities in health affirming life conditions and improving social cohesion across diverse groups to take action to improve theses condition lay at the heart of this strategy. PMID- 27405728 TI - Safety and advantages of combined resection and microwave ablation in patients with bilobar hepatic malignancies. AB - BACKGROUND: The multimodality approach has significantly improved outcomes for hepatic malignancies. Microwave ablation is often used in isolation or succession, and seldom in combination with resection. Potential benefits and pitfalls from combined resection and ablation therapy in patients with complex and extensive bilobar hepatic disease have not been well defined. METHODS: A review of the University of Louisville prospective Hepato-Pancreatico-Biliary Patients database was performed with multi-focal bilobar disease that underwent microwave ablation with resection or microwave only included. RESULTS: One hundred and eight were treated with microwave only (MWA, n = 108) or combined resection and ablation (CRA, n = 84) and were compared with similar disease burden patients undergoing resection only (n = 84). The groups were comparable except that the MWA group was older (p = .02) and with higher co-morbidities (diabetes, hepatitis). The resection group had larger tumours (4 vs. 3.2 and 3 cm) but the CRA group had more numerous lesions (4 vs. 3 and 2, p = .002). Short term outcomes including morbidity (47.6% vs. 43%, p = .0715) were similar between the CRA and resection only groups. Longer operative time (164 vs. 126 min, p = .003) and need for blood transfusion (p = .001) were independent predictors of complications. Survival analyses for colorectal metastasis patients (n = 158) demonstrated better overall survival (OS) (43.9 vs. 37.6 and 30.5 months, p = .035), disease-free survival (DFS) (38 vs. 26.6 and 16.9 months, p = .028) and local recurrence-free survival (LRFS) (55.4 vs. 17 and 22.9 months, p < .001) with resection only. CONCLUSION: The use of microwave ablation in addition to surgical resection did not significantly increase the morbidities or short-term outcomes. In combination with systemic and other local forms of therapy, combined resection and ablation is a safe and effective procedure. PMID- 27405729 TI - DNA replication inhibitor hydroxyurea alters Fe-S centers by producing reactive oxygen species in vivo. AB - Redox homeostasis is tightly controlled in cells as it is critical for most cellular functions. Iron-Sulfur centers (Fe-S) are metallic cofactors with electronic properties that are associated with proteins and allow fine redox tuning. Following the observation that altered Fe-S biosynthesis is correlated with a high sensitivity to hydroxyurea (HU), a potent DNA replication blocking agent, we identified that oxidative stress response pathway under the control of the main regulator Yap1 attenuates HU deleterious effects, as it significantly increases resistance to HU, Fe-S biosynthesis and DNA replication kinetics in the presence of HU. Yap1 effect is mediated at least in part through up-regulation of two highly conserved genes controlling cytosolic Fe-S biosynthesis and oxidative stress, Dre2 and Tah18. We next observed that HU produces deleterious effects on cytosolic Fe-S clusters in proteins in vivo but not in vitro, suggesting that HU's impact on Fe-S in vivo is mediated by cellular metabolism. Finally, we evidenced that HU exposure was accompanied by production of reactive oxygen species intracellularly. Altogether, this study provides mechanistic insight on the initial observation that mutants with altered Fe-S biosynthesis are highly sensitive to HU and uncovers a novel mechanism of action of this widely used DNA replication inhibitor. PMID- 27405731 TI - Highly sensitive detection of the PIK3CA (H1047R) mutation in colorectal cancer using a novel PCR-RFLP method. AB - BACKGROUND: The PIK3CA (H1047R) mutation is considered to be a potential predictive biomarker for EGFR-targeted therapies. In this study, we developed a novel PCR-PFLP approach to detect the PIK3CA (H1047R) mutation in high effectiveness. METHODS: A 126-bp fragment of PIK3CA exon-20 was amplified by PCR, digested with FspI restriction endonuclease and separated by 3 % agarose gel electrophoresis for the PCR-RFLP analysis. The mutant sequence of the PIK3CA (H1047R) was spiked into the corresponding wild-type sequence in decreasing ratios for sensitivity analysis. Eight-six cases of formalin-fixed paraffin embedded colorectal cancer (CRC) specimens were subjected to PCR-RFLP to evaluate the applicability of the method. RESULTS: The PCR-RFLP method had a capability to detect as litter as 0.4 % of mutation, and revealed 16.3 % of the PIK3CA (H1047R) mutation in 86 CRC tissues, which was significantly higher than that discovered by DNA sequencing (9.3 %). A positive association between the PIK3CA (H1047R) mutation and the patients' age was first found, except for the negative relationship with the degree of tumor differentiation. In addition, the highly sensitive detection of a combinatorial mutation of PIK3CA, KRAS and BRAF was achieved using individual PCR-RFLP methods. CONCLUSIONS: We developed a sensitive, simple and rapid approach to detect the low-abundance PIK3CA (H1047R) mutation in real CRC specimens, providing an effective tool for guiding cancer targeted therapy. PMID- 27405734 TI - Quercetin 3,7-O-dimethyl ether from Siegesbeckia pubescens suppress the production of inflammatory mediators in lipopolysaccharide-induced macrophages and colon epithelial cells. AB - Siegesbeckia pubescens (Compositae) is an annual herb indigenous to Korean mountainous regions. Recent reports have been issued on some compounds derived from S. pubescens for its anti-inflammatory activity or mode of action. The quercetin 3,7-O-dimethyl ether (QDE) isolated from the herbs of S. pubescens suppressed the lipopolysaccharide (LPS)-induced nitric oxide and inducible nitric oxide synthase (iNOS) protein production in mouse macrophages. QDE downregulated pro-inflammatory cytokines such as interleukin (IL)-6, IL-1beta, tumor necrosis factor -alpha levels in LPS-stimulated macrophages. Also, QDE decreased the expression of LPS-induced iNOS and cyclooxygenase-2 (COX-2) protein and the production of IL-8 in LPS-induced HT-29 cells. Macrophages and colon epithelial cells are important for regulating the colon immune systems, thus QDE may regulate inflammatory colon disease via LPS-induced inflammation in macrophages and colon epithelial cells. QDE, anti-inflammatory constituent of S. pubescens herbs, can be expected to be a potential candidate for therapeutics against inflammatory bowel disease. PMID- 27405735 TI - Regional block: who first thought of such an approach? PMID- 27405732 TI - Seven-year follow-up for energy/vitality outcomes in early stage Hodgkin's disease patients treated with subtotal lymphoid irradiation versus chemotherapy plus radiation: SWOG S9133 and its QOL companion study, S9208. AB - PURPOSE: We describe 7 years of follow-up for the energy/vitality outcome in early-stage Hodgkin's disease patients treated on a randomized clinical trial that compared subtotal lymphoid irradiation (STLI) with combined modality treatment (CMT) (SWOG 9133). Survivorship research questions involved the extent to which symptoms/side effects endured over a follow-up period of 7 years for this early-stage patient group. METHODS: Two hundred thirty-nine patients participated in the quality of life (QOL) companion study (SWOG 9208) and completed the SF-36 vitality scale, SF-36 health perception item, Cancer Rehabilitation Evaluation System-Short Form (CARES-SF), and symptom distress scale. This paper reports vitality outcome results obtained from randomization, 6 months, and annually for 7 years. To assess changes in vitality over time, we used linear mixed models with patient as a random effect. RESULTS: Patients receiving CMT had lower observed vitality at 6 months than did the STLI patients (p < .0001). However, beginning at year 1, vitality results did not differ significantly by treatment over the 5-year (p = .13) and 7-year (p = .16) follow up periods. Vitality only slightly improved over baseline in either group after treatment. The results were similar after accounting for patterns of recurrence and missing data. CONCLUSIONS: This study demonstrated that patients with early stage Hodgkin's disease experience a short-term (at 6 months) decrease in vitality with treatment, which is more severe with CMT, but that after the first year, vitality scores were similar between the two treatment groups. Enduring fatigue results for patients receiving these therapies were not observed. Implications for cancer survivors These data provide comprehensive 7-year follow up vitality information, an important symptom for early-stage lymphoma survivors. PMID- 27405733 TI - Influence of chitosan-sodium alginate pretreated with ultrasound on the enzyme activity, viscosity and structure of papain. AB - BACKGROUND: Ultrasound treatment has been shown to be an effective technique for improving the activity of immobilized enzymes. However, its mechanism is unclear. RESULTS: The effect of ultrasonic pretreated chitosan-sodium alginate (CHI-ALG) on the enzymatic activity of papain was investigated via a single factor (temperature, time, frequency, power) experiment. The maximum relative enzyme activity of papain was observed when it was mixed with ultrasound pretreated CHI ALG at 135 kHz, 0.25 W cm-2 and 50 degrees C for 20 min, during which the relative activity increased by 72.14% compared to untreated CHI-ALG. Viscosity analysis of papain mixed with CHI-ALG pretreated and untreated with ultrasound revealed that stronger association interactions between the polymers were formed compared to the untreated sample. Fluorescence and circular dichroism spectra indicated that the ultrasonic pretreatment of CHI-ALG increased the number of tryptophan on the papain surface and also increased the content of alpha-helix by 6.97% and decreased the content of beta-sheet by 3.45% compared to the untreated solution. CONCLUSION: The results of the present study indicate that papain combined with CHI-ALG pretreated with the appropriate ultrasound could be effective technique for improving the activity of immobilized enzymes as a result of changes in its structure and intermolecular interactions. It is important to extend the application of CHI-ALG gel in the immobilized enzyme industry. (c) 2016 Society of Chemical Industry. PMID- 27405736 TI - Do not hear, see, or speak: views of older residents and their adult children about the nursing unit in the continuing care retirement community. AB - BACKGROUND: The present study evaluated views of continuing care retirement community (CCRC) residents and their adult children concerning the nursing unit (NU) within the CCRC. METHODS: Qualitative interviews with older adults and their adult children were conducted. Analysis consisted of 187 interviews with older adults and their adult children over a period of up to six years. Analysis relied on constant comparisons within the same interview, over interviews of the same person over time, and between CCRC residents and their adult children. Major themes were identified to construct a coherent storyline. RESULTS: The NU was viewed as a different universe that should be avoided at all costs. This was attributed to: (1) the association of the NU with one's impending decline and dependence and (2) beliefs about substandard care in the NU. CONCLUSIONS: The findings point to the ambivalence expressed by CCRC residents and their adult children concerning the NU, even though to some degree, the NU represents the main reason for the transition to a CCRC. PMID- 27405737 TI - The junior doctor contract: we now need strong leadership at all levels. PMID- 27405738 TI - Zika Virus-Associated Microcephaly and Eye Lesions in the Newborn. AB - On February 1, 2016, Zika virus (ZIKV) was designated as a Public Health Emergency of International Concern by the director of the World Health Organization. Zika virus has spread to numerous countries throughout the Americas, affecting up to an estimated 1.3 million people since the first reports from Brazil in early 2015. Although ZIKV infections are self-limiting, fetal microcephaly and ophthalmic anomalies have been associated with ZIKV infection as a possible result of perinatal transmission. The causal link between maternal ZIKV infection and newborn microcephaly and eye lesions has not been proven beyond doubt and is currently debated. We discuss the possibility of causality by ZIKV using Koch's postulates and the more appropriate Bradford Hill criteria. In this review, we summarize and consolidate the current literature on newborn microcephaly and eye lesions associated with ZIKV infection and discuss current perspectives and controversies. PMID- 27405739 TI - Partial characterization and antioxidant and antiproliferative activities of the aqueous extracellular polysaccharides from the thermophilic microalgae Graesiella sp. AB - BACKGROUND: For thousands of years, Tunisian geothermal water has been used in bathing. Indeed, thermal baths "Hammam" were recommended in the treatment of different type of illnesses as, for instance, for relaxing joints and soothing. The ability of microalgae to sustain at the high temperature makes them potential producers of high value thermostable bio-products. This study aimed to explore the therapeutic potential of the aqueous extracellular polysaccharides (AEPS) of the Tunisian thermophilic microalgae Graesiella sp. and to evaluate its physico chemical characteristics. METHODS: Different parameters were used to characterize the AEPS. The dry weight, volatile dry weight, elemental analysis, monosaccharide composition and IR-spectroscopy analysis. Carbohydrate, uronic acid, ester sulfate and protein concentrations were also determined using colorimetric assay. AEPS was analyzed for its antioxidant propriety by means of total antioxidant capacity, DPPH radicals scavenging assay, ferrous chelating ability and hydroxyl and superoxide radical scavenging activity. The antiproliferative activity of AEPS was evaluated for HepG2 and Caco-2 cells using the MTT assay. RESULTS: The Graesiella sp. AEPS is found to be a hetero-sulfated-anionic polysaccharides that contain carbohydrate (52 %), uronic acids (23 %), ester sulfate (11 %) and protein (12 %). The carbohydrate fraction was formed by eight neutral sugars glucose, galactose, mannose, fucose, rhamnose, xylose, arabinose and ribose. The FT-IR revealed the presence of carboxyl, hydroxyl, amine and sulfate groups. AEPS showed high activity as reducing agent, high ferrous chelating capacity and caused a significant decrease in a concentration-dependent manner of hydroxyl radical. A moderate DPPH scavenging activity and a poor superoxide radical scavenging ability were also observed. AEPS treatment (from 0.01 to 2.5 mg/ml) caused also a clear decrease of cell viabilities in a dose-dependent manner. The IC50 values obtained in HepG2 and Caco-2 cells were 1.06 mg/ml and 0.3 mg/ml respectively. CONCLUSIONS: This study evidenced that the Graesiella sp. AEPS exhibits antioxidant and antiproliferative activities. The biological activities of this extract depend on its fine structural features. Further work will identify and purify the active polysaccharides to enhance our understanding of their complete structure and relationships with its function. PMID- 27405741 TI - Tailored ionic liquid-based surfactants for the formation of microemulsions with water and a hydrophobic ionic liquid. AB - Microemulsions (MUe) with water and a hydrophobic ionic liquid (IL) usually require 45-60 wt% surfactant to solubilize equal amounts of water and IL. To increase the efficiency we designed a new class of surfactants by combining a hydrophilic but IL-ophobic carbohydrate-based part with a hydrophobic but IL ophilic IL-based part. These surfactants allow formulating microemulsions with 20 wt% surfactant only which opens up a new arena for efficient water-IL MUes. PMID- 27405740 TI - Does adenoid hypertrophy affect disease severity in children with allergic rhinitis? AB - Our study aims to evaluate the presence of adenoid hypertrophy (AH) in children with allergic rhinitis (AR) and the association of AH disease severity and clinical laboratory finding from retrospective, cross-sectional, and nonrandomized trial. The study included 566 children being treated and followed up for allergic rhinitis. Skin prick test for the same allergens was performed for all patients. Adenoid tissue was analyzed by an ENT specialist and the diagnosis was confirmed based on the patient history, endoscopic physical examination and radiology. Adenoid hypertrophy was detected in 118 (21.2 %) of the children with AR. Children with and without AH did not differ statistically and significantly by gender, age, presence of atopy in the family, exposure to smoke (p > 0.05). Comparison of the groups for AR duration demonstrated significantly higher frequency of persistent rhinitis in patients with AH (p < 0.05). Of the AR patients with AH, 90 (76.3 %) had moderate-severe rhinitis and 274 (62.6 %) AR patients without AH had moderate-severe rhinitis (p = 0.005). Itchy nose was more frequent in AR patients without AH, and nasal congestion was more common in AR patients with AH (p = 0.017 and p = 0.001, respectively). The presence of asthma was more common among AR patients without AH (p = 0.037). Intergroup comparisons for presence of atopic dermatitis, the percentage of eosinophil, serum IgE levels, the number of positive sensitivity, polysensitization, sensitivity to house dust mite, cockroach, pollens and dander yielded no significant difference (p > 0.05). On the other hand, sensitivity to Alternaria alternata was significantly more frequent in AR patients with AH (p = 0.032). The presence of AH increased the severity of the disease and prolongs disease duration. There was a negative relationship between AH and asthma in children with AR. AH is more common among children with mold sensitivity. AH should be considered and investigated particularly in non-asthmatic children with pronounced nasal congestion and A. alternata sensitivity. PMID- 27405742 TI - Prevalence, impact and treatment of generalised anxiety disorder in bipolar disorder: a systematic review and meta-analysis. AB - QUESTION: Recent data suggest that anxiety disorders are as often comorbid with bipolar disorder (BD) as with unipolar depression; however, less attention has been paid to comorbidity of anxiety disorders with BD. Generalised anxiety disorder (GAD) is one of the most prevalent anxiety disorders that is highly comorbid with other mental disorders. We carried out a systematic review and meta analysis to assess the degree of comorbidity between GAD and BD. STUDY SELECTION AND ANALYSIS: We searched for all studies, which included primary data concerning the existence of GAD in patients with BD. The literature search strategy, selection of publications and the reporting of results have been conducted with PRISMA guidelines. The meta-analysis calculated prevalence estimates using the variance-stabilising Freeman-Tukey double arcsine transformation. We applied the inverse variance method using both fixed-effects and random-effects models to estimate summary effects for all combined studies. Heterogeneity was assessed and measured with Cochran's Q and I(2) statistics, respectively. FINDINGS: The current meta-analysis analysed data from 28 independent studies and a total of 2975 patients from point prevalence studies and 4919 patients from lifetime studies. The overall random-effects point prevalence of GAD in patients with BD was 12.2% (95% CI 10.9% to 13.5%) and the overall random-effects lifetime estimate was 15.1% (95% CI 9.7% to 21.5%). Both estimates reported significant heterogeneity (94.0% and 94.7%, respectively). CONCLUSIONS: Published studies report prevalence rates with high heterogeneity and consistently higher than those typically reported in the general population. It is believed that comorbid GAD might be associated with a more severe BD course and increased suicidality, and it is unknown how best to treat such conditions. The current meta-analysis confirms that GAD is highly prevalent in BD and the rate is higher in comparison to those in the general population. PMID- 27405743 TI - Quality and impact of secondary information in promoting evidence-based clinical practice: a cross-sectional study about EBMH. AB - BACKGROUND: All mental health professionals are encouraged to practise evidence based medicine, but in an era of overwhelming research output, information management is key. Until now, no one has assessed the role of secondary journals, which aim to synthesise and present recent evidence, so as to promote evidence based practice. OBJECTIVE: We conducted a cross-sectional study via an online survey, to evaluate the quality of the content of Evidence-Based Mental Health (EBMH), as an example of a secondary journal, and the impact it has on evidence based practice. METHODS: We sent an online questionnaire to the commentators and the original study authors of all commentaries published in EBMH over the past 5 years (from 2011 to 2015, inclusive). The questions primarily concerned the quality of the included papers and their respective commentary, in addition to the ability of the commentaries to help disseminate research findings and promote evidence-based practice. FINDINGS: We sent out 894 anonymous questionnaires and the overall response rate was 30%. The commentator and study author groups were largely homogeneous. Both groups were satisfied with the format and content of the commentaries, although over 60% of the authors were unaware of the commentary on their study before the survey. Notably, 80% of authors and 87% of commentators felt that the commentaries were useful in disseminating the findings of the original studies and implementing evidence-based practice. CONCLUSIONS AND CLINICAL IMPLICATIONS: The commentators and original study authors view EBMH not as a vehicle for criticism, but instead as a trustworthy publication that crystallises important findings and presents them in digestible form with the aim of promoting key advances in mental health. Next, we aim to assess the extent to which the readership of this journal agrees. PMID- 27405744 TI - On variation and uncertainty. PMID- 27405746 TI - You Only Die Once: Accounting for Multi-Attributable Mortality Risks in Multi Disease Models for Health-Economic Analyses. AB - Mortality rates in Markov models, as used in health economic studies, are often estimated from summary statistics that allow limited adjustment for confounders. If interventions are targeted at multiple diseases and/or risk factors, these mortality rates need to be combined in a single model. This requires them to be mutually adjusted to avoid 'double counting' of mortality. We present a mathematical modeling approach to describe the joint effect of mutually dependent risk factors and chronic diseases on mortality in a consistent manner. Most importantly, this approach explicitly allows the use of readily available external data sources. An additional advantage is that existing models can be smoothly expanded to encompass more diseases/risk factors. To illustrate the usefulness of this method and how it should be implemented, we present a health economic model that links risk factors for diseases to mortality from these diseases, and describe the causal chain running from these risk factors (e.g., obesity) through to the occurrence of disease (e.g., diabetes, CVD) and death. Our results suggest that these adjustment procedures may have a large impact on estimated mortality rates. An improper adjustment of the mortality rates could result in an underestimation of disease prevalence and, therefore, disease costs. PMID- 27405745 TI - Physical activity preferences of individuals diagnosed with schizophrenia or bipolar disorder. AB - BACKGROUND: Individuals with a severe mental illness (SMI) are at least two times more likely to suffer from metabolic co-morbidities, leading to excessive and premature deaths. In spite of the many physical and mental health benefits of physical activity (PA), individuals with SMI are less physically active and more sedentary than the general population. One key component towards increasing the acceptability, adoption, and long-term adherence to PA is to understand, tailor and incorporate the PA preferences of individuals. Therefore, the objective of this study was to determine if there are differences in PA preferences among individuals diagnosed with different psychiatric disorders, in particular schizophrenia or bipolar disorder (BD), and to identify PA design features that participants would prefer. METHODS: Participants with schizophrenia (n = 113) or BD (n = 60) completed a survey assessing their PA preferences. RESULTS: There were no statistical between-group differences on any preferred PA program design feature between those diagnosed with schizophrenia or BD. As such, participants with either diagnosis were collapsed into one group in order to report PA preferences. Walking (59.5 %) at moderate intensity (61.3 %) was the most popular activity and participants were receptive to using self-monitoring tools (59.0 %). Participants were also interested in incorporating strength and resistance training (58.5 %) into their PA program and preferred some level of regular contact with a fitness specialist (66.0 %). CONCLUSIONS: These findings can be used to tailor a physical activity intervention for adults with schizophrenia or BD. Since participants with schizophrenia or BD do not differ in PA program preferences, the preferred features may have broad applicability for individuals with any SMI. PMID- 27405747 TI - Polymorphism of IL-10 receptor beta affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib. AB - Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) single nucleotide polymorphisms have been implicated in the pathogenesis of many cancers. We investigated the influence of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E on the risk of developing multiple myeloma (MM) and the clinical features of MM. We extracted the genomic DNA from 128 MM patients and 202 healthy controls and used polymerase chain reaction-restriction fragment length polymorphism method to detect IL-10 promoter -592C/A (rs1800872), IL-10RA (rs2228055), and IL-10RB K47E (rs2834167) genotypes. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment. No statistically significant difference was observed in the genotype and allele frequencies of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E between MM patients and healthy controls. IL-10RA II genotype was significantly associated with a hemoglobin level lower than that of IV and VV genotypes (mean +/- standard deviation, 9.21 +/- 2.46 vs 10.3 +/- 2.33 g/dL; P = .021). IL-10 -592 AA genotype was significantly associated with OS better than that of CA and CC genotypes (median OS, 74.5 vs 46.3 months; P = .047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and those treated with conventional treatments (median OS, 74.5 vs 38.2 months; P = .021). Therefore, we also examined the effect of IL-10 and IL-10R polymorphisms on the clinical variables and OS of patients treated with thalidomide and/or bortezomib. In addition, IL-10RB EE genotype was significantly associated with poorer survival than KK and KE genotypes (median OS, 46.3 vs 78.8 months; P = .015). Our findings indicate that IL-10 and IL-10R gene polymorphisms may not contribute to the susceptibility to MM but may be associated with the severity and prognosis of MM. In particular, IL-10RB K47E polymorphism may contribute to the poor prognosis of MM patients treated with thalidomide and/or bortezomib. PMID- 27405748 TI - Analysis of Prehospital Transport Use for Trauma Patients in Lusaka, Zambia. AB - : Despite an increasing burden of injuries, prehospital transport systems remain underdeveloped in many low- and middle-income countries. Little information exists on the use of prehospital services for trauma patients in Zambia. METHOD: A prospective, observational study of trauma presentations was undertaken for 6 months in Lusaka, Zambia, to establish the epidemiology and outcomes of injury in the region. In addition to demographics and mechanism of injury, data were collected on prehospital transport as well as inpatient resources utilization. Trained study personnel gathered data on trauma presentations 24 h a day. Statistical analysis was conducted using SAS 9.3 from a Microsoft(r) Access database. RESULTS: 3498 trauma patients were enrolled in the study on arrival to University Teaching Hospital (UTH). 3264 patients had a transport means recorded (95.3 %). Two-thirds (66 %) arrived within 6 h of injury, and 23 % arrived within the first hour after injury. A majority arrived by private vehicle (53.4 %) or public transport (37.7 %); only 5.9 % were transported by public or private ambulance. Of those arriving within the first hour after injury, 69.1 % came by private car, 24.6 % by public transport and 3.1 % by ambulance. There was a small statistical increase in Kampala Trauma Score II among ambulance arrivals. CONCLUSION: Trauma patient use a variety of transport methods to get to UTH. A majority of patients use no formal ambulance transport. Despite this fact, a majority arrives within 6 h of injury but receive no formal prehospital care. An integrated, multilayered prehospital care and transport system may be the most effective approach for Zambia. PMID- 27405749 TI - Randomized Clinical Trial of Moderate Versus Deep Neuromuscular Block for Low Pressure Pneumoperitoneum During Laparoscopic Cholecystectomy. AB - BACKGROUND: The beneficial effects of deep blockade are not fully known. In this study, we evaluated the effect of deep neuromuscular blockade on surgical conditions during laparoscopic cholecystectomy under low-pressure pneumoperitoneum. METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomized to either the moderate group (train-of-four count of 1 or 2) or deep group (posttetanic count of 1 or 2). Neuromuscular blockade was induced and maintained with rocuronium; it was reversed with sugammadex in the deep group and with neostigmine in the moderate group. At the beginning of surgery, the intra-abdominal pressure was set at 8 mmHg. The surgeon rated the surgical condition on a 4-point scale (1 = excellent, 2 = good, 3 = acceptable, 4 = poor) and was allowed to increase the pressure to 12 mmHg if it was determined that the surgical conditions were inadequate for the operation. RESULTS: A total of 64 patients completed the study. The rate of increasing intra-abdominal pressure to maintain optimal surgical conditions was 34.4 % in the moderate group and 12.5 % in the deep group (P = 0.039). The proportion of patients with a surgical condition score of 1 or 2 (excellent or good) was 34.4 % in the moderate group and 68.8 % in the deep group (P = 0.006). CONCLUSION: The maintenance of intraoperative deep neuromuscular blockade was associated with a lower rate of conversion to standard pressure and higher surgeon satisfaction with the surgical conditions than was moderate blockade in patients undergoing low-pressure pneumoperitoneum laparoscopic cholecystectomy. PMID- 27405750 TI - East or West, Who Grades Liver Failure After Liver Resection for Perihilar Cholangiocarcinoma Best? PMID- 27405751 TI - Human serum-derived protein removes the need for coating in defined human pluripotent stem cell culture. AB - Reliable, scalable and time-efficient culture methods are required to fully realize the clinical and industrial applications of human pluripotent stem (hPS) cells. Here we present a completely defined, xeno-free medium that supports long term propagation of hPS cells on uncoated tissue culture plastic. The medium consists of the Essential 8 (E8) formulation supplemented with inter-alpha inhibitor (IalphaI), a human serum-derived protein, recently demonstrated to activate key pluripotency pathways in mouse PS cells. IalphaI efficiently induces attachment and long-term growth of both embryonic and induced hPS cell lines when added as a soluble protein to the medium at seeding. IalphaI supplementation efficiently supports adaptation of feeder-dependent hPS cells to xeno-free conditions, clonal growth as well as single-cell survival in the absence of Rho associated kinase inhibitor (ROCKi). This time-efficient and simplified culture method paves the way for large-scale, high-throughput hPS cell culture, and will be valuable for both basic research and commercial applications. PMID- 27405752 TI - Study protocol for a cluster randomized controlled trial to evaluate a referral strategy for axial spondyloarthritis in young primary care patients with chronic low back pain; an impact study. AB - BACKGROUND: Axial spondyloarthritis (axSpA) is a disabling inflammatory joint disease with chronic low back pain (CLBP) as leading symptom. Recognizing axSpA in the large amount of CLBP patients is difficult for general practioners (GP). This evaluation aims to assess the effect of a referral strategy for axSpA in young primary care patients with CLBP by comparing the use of the strategy with usual care. The effect is measured at three different levels; by patient reported outcomes (the clinical effect), process and costs evaluation. METHODS/DESIGN: This study design is a cluster randomized controlled trial with GP as clusters. GPs throughout the Netherlands are invited to participate and randomized to either the intervention or the control group. Patients from participating GPs are invited to participate if they have ever been registered with low back pain, without radiation (ICPC L03) and aged 18-45 years. To be included in the study, patients need to have current low back pain and chronic low back pain (>12 weeks). In the intervention arm a referral strategy for axSpA will be applied in CLBP patients, in the control arm care as usual will be provided for CLBP patients. The referral strategy consists of four easy to use variables. All are questions about the back pain complaints of the patients. Data is prospectively collected in an online database at baseline (T0), 4 months (T1), 12 months (T2) and 24 months (T3). After time point T1 (4 months) patients from the control group will also receive the intervention i.e. the application of a referral strategy for axSpA. The effect of the referral strategy is measured at three different levels, by patient outcomes (e.g. pain scores, quality of life), process measures (e.g. number of axSpA diagnoses by rheumatologists) and by costs (work productivity and health care resources use). Our primary outcome is the Roland Morris Disability Questionnaire after 4 months, secondary outcomes are pain and quality of life. Costs will be assessed before and after the use of the referral strategy, to estimate if the use of the strategy will lead to a reduction in health care costs and improvement in work participation. DISCUSSION: It is anticipated that using the axSpA referral strategy for primary care CLBP patients will increase the quality of life of CLBP patients, will result in more (correct) diagnoses of axSpA by the rheumatologists, and will be cost-effective. Ultimately, the results of this study may contribute to the startup of a national implementation of the axSpA referral strategy to identify timely CLBP patients with axSpA. TRIAL REGISTRATION: NCT01944163 , date of registration; September 6, 2013 (Clinicaltrials.gov). PMID- 27405754 TI - Phenotypic characterization of human cytomegalovirus strains in cell cultures based on their transmission kinetics. AB - We established a new 'transmission kinetic assay (TKA)' to quantify the human cytomegalovirus (HCMV) transmission between cells in vitro and to phenotypically characterize HCMV strains based on their mode of transmission by flow cytometric analysis. On one hand we used the genetically modified HCMV strain TB40/E-delUL16 GFP, and on the other hand, clinical isolates. When twofold diluted infecting cells were seeded to a constant number of uninfected cells, the transmission of virus on each day (day 0-5) followed a strictly linear pattern, which was characterized by a linear equation. The slope of this linear equation represents 'the number of newly infected cells per infecting cell'. To standardize the TKA, the slopes of the different days were plotted against the corresponding days. This resulted in a new linear equation with a new slope value, which characterizes the transmission kinetics. To differentiate cell-associated and cell-free modes of transmission, we introduced HCMV neutralizing antibodies into the system. The slope was 0.9 (+/-0.5) when the virus exhibited only cell associated transmission and was 4.1 (+/-0.7) when the virus exhibited both modes of transmission. TKA was then applied to different clinical isolates and they were phenotypically characterized based on their modes of transmission. Apart from the quantitative analysis of HCMV transmission and the phenotypical characterization of clinical isolates, the TKA was applied to quantify the inhibition of clinical isolates transmission by immune cells and to study the effect of cytokine (IL-2) on immune cells inhibiting HCMV transmission. PMID- 27405755 TI - The San1 Ubiquitin Ligase Functions Preferentially with Ubiquitin-conjugating Enzyme Ubc1 during Protein Quality Control. AB - Protein quality control (PQC) is a critical process wherein misfolded or damaged proteins are cleared from the cell to maintain protein homeostasis. In eukaryotic cells, the removal of misfolded proteins is primarily accomplished by the ubiquitin-proteasome system. In the ubiquitin-proteasome system, ubiquitin conjugating enzymes and ubiquitin ligases append polyubiquitin chains onto misfolded protein substrates signaling for their degradation. The kinetics of protein ubiquitylation are paramount as a balance must be achieved between the rapid removal of misfolded proteins versus providing sufficient time for protein chaperones to attempt refolding. To uncover the molecular basis for how PQC substrate ubiquitylation rates are controlled, the reaction catalyzed by nuclear ubiquitin ligase San1 was reconstituted in vitro Our results demonstrate that San1 can function with two ubiquitin-conjugating enzymes, Cdc34 and Ubc1. Although Cdc34 and Ubc1 are both sufficient for promoting San1 activity, San1 functions preferentially with Ubc1, including when both Ubc1 and Cdc34 are present. Notably, a homogeneous peptide that mimics a misfolded PQC substrate was developed and enabled quantification of the kinetics of San1-catalyzed ubiquitylation reactions. We discuss how these results may have broad implications for the regulation of PQC-mediated protein degradation. PMID- 27405756 TI - Structural Insight into Substrate Selection and Catalysis of Lipid Phosphate Phosphatase PgpB in the Cell Membrane. AB - PgpB belongs to the lipid phosphate phosphatase protein family and is one of three bacterial integral membrane phosphatases catalyzing dephosphorylation of phosphatidylglycerol phosphate (PGP) to generate phosphatidylglycerol. Although the structure of its apo form became recently available, the mechanisms of PgpB substrate binding and catalysis are still unclear. We found that PgpB was inhibited by phosphatidylethanolamine (PE) in a competitive mode in vitro Here we report the crystal structure of the lipid-bound form of PgpB. The structure shows that a PE molecule is stabilized in a membrane-embedded tunnel formed by TM3 and the "PSGH" fingerprint peptide near the catalytic site, providing structural insight into PgpB substrate binding mechanism. Noteworthy, in silico docking of varied lipid phosphates exhibited similar substrate binding modes to that of PE, and the residues in the lipid tunnel appear to be important for PgpB catalysis. The catalytic triad in the active site is essential for dephosphorylating substrates lysophosphatidic acid, phosphatidic acid, or sphingosine-1-phosphate but surprisingly not for the native substrate PGP. Remarkably, residue His-207 alone is sufficient to hydrolyze PGP, indicating a specific catalytic mechanism for PgpB in PG biosynthesis. We also identified two novel sensor residues, Lys-93 and Lys-97, on TM3. Our data show that Lys-97 is essential for the recognition of lyso-form substrates. Modification at the Lys-93 position may alter substrate specificity of lipid phosphate phosphatase proteins in prokaryotes versus eukaryotes. These studies reveal new mechanisms of lipid substrate selection and catalysis by PgpB and suggest that the enzyme rests in a PE-stabilized state in the bilayer. PMID- 27405757 TI - Controlling PTEN (Phosphatase and Tensin Homolog) Stability: A DOMINANT ROLE FOR LYSINE 66. AB - Phosphatase and tensin homolog (PTEN) is a phosphoinositide lipid phosphatase and one of the most frequently disrupted tumor suppressors in many forms of cancer, with even small reductions in the expression levels of PTEN promoting cancer development. Although the post-translational ubiquitination of PTEN can control its stability, activity, and localization, a detailed understanding of how PTEN ubiquitination integrates with other cellular regulatory processes and may be dysregulated in cancer has been hampered by a poor understanding of the significance of ubiquitination at individual sites. Here we show that Lys(66) is not required for cellular activity, yet dominates over other PTEN ubiquitination sites in the regulation of protein stability. Notably, combined mutation of other sites (Lys(13), Lys(80), and Lys(289)) has relatively little effect on protein expression, protein stability, or PTEN polyubiquitination. The present work identifies a key role for Lys(66) in the regulation of PTEN expression and provides both an opportunity to improve the stability of PTEN as a protein therapy and a mechanistic basis for efforts to stabilize endogenous PTEN. PMID- 27405758 TI - Transforming Growth Factor-beta1 Increases DNA Methyltransferase 1 and 3a Expression through Distinct Post-transcriptional Mechanisms in Lung Fibroblasts. AB - DNA methylation is a fundamental epigenetic mark that plays a critical role in differentiation and is mediated by the actions of DNA methyltransferases (DNMTs). TGF-beta1 is one of the most potent inducers of fibroblast differentiation, and although many of its actions on fibroblasts are well described, the ability of TGF-beta1 to modulate DNA methylation in mesenchymal cells is less clear. Here, we examine the ability of TGF-beta1 to modulate the expression of various DNMTs in primary lung fibroblasts (CCL210). TGF-beta1 increased the protein expression, but not RNA levels, of both DNMT1 and DNMT3a. The increases in DNMT1 and DNMT3a were dependent on TGF-beta1 activation of focal adhesion kinase and PI3K/Akt. Activation of mammalian target of rapamycin complex 1 by Akt resulted in increased protein translation of DNMT3a. In contrast, the increase in DNMT1 by TGF-beta1 was not dependent on new protein synthesis and instead was due to decreased protein degradation. TGF-beta1 treatment led to the phosphorylation and inactivation of glycogen synthase kinase-3beta, which resulted in inhibition of DNMT1 ubiquitination and proteosomal degradation. The phosphorylation and inactivation of glycogen synthase kinase-3beta was dependent on mammalian target of rapamycin complex 1. These results demonstrate that TGF-beta1 increases expression of DNMT1 and DNMT3a through different post-transcriptional mechanisms. Because DNA methylation is critical to many processes including development and differentiation, for which TGF-beta1 is known to be crucial, the ability of TGF beta1 to increase expression of both DNMT1 and DNMT3a demonstrates a novel means by which TGF-beta1 may regulate DNA methylation in these cells. PMID- 27405759 TI - Amino Groups of Chitosan Are Crucial for Binding to a Family 32 Carbohydrate Binding Module of a Chitosanase from Paenibacillus elgii. AB - We report here the role and mechanism of specificity of a family 32 carbohydrate binding module (CBM32) of a glycoside hydrolase family 8 chitosanase from Paenibacillus elgii (PeCsn). Both the activity and mode of action of PeCsn toward soluble chitosan polymers were not different with/without the CBM32 domain of P. elgii (PeCBM32). The decreased activity of PeCsn without PeCBM32 on chitosan powder suggested that PeCBM32 increases the relative concentration of enzyme on the substrate and thereby enhanced enzymatic activity. PeCBM32 specifically bound to polymeric and oligomeric chitosan and showed very weak binding to chitin and cellulose. In isothermal titration calorimetry, the binding stoichiometry of 2 and 1 for glucosamine monosaccharide (GlcN) and disaccharide (GlcN)2, respectively, was indicative of two binding sites in PeCBM32. A three-dimensional model-guided site-directed mutagenesis and the use of defined disaccharides varying in the pattern of acetylation suggested that the amino groups of chitosan and the polar residues Glu-16 and Glu-38 of PeCBM32 play a crucial role for the observed binding. The specificity of CBM32 has been further elucidated by a generated fusion protein PeCBM32-eGFP that binds to the chitosan exposing endophytic infection structures of Puccinia graminis f. sp. tritici Phylogenetic analysis showed that CBM32s appended to chitosanases are highly conserved across different chitosanase families suggesting their role in chitosan recognition and degradation. We have identified and characterized a chitosan-specific CBM32 useful for in situ staining of chitosans in the fungal cell wall during plant fungus interaction. PMID- 27405760 TI - Functional Consequences of Mannose and Asialoglycoprotein Receptor Ablation. AB - The mannose receptor (ManR, Mrc1) and asialoglycoprotein receptor (ASGR, Asgr1 and Asgr2) are highly abundant endocytic receptors expressed by sinusoidal endothelial cells and parenchymal cells in the liver, respectively. We genetically manipulated either receptor individually or in combination, revealing phenotypic changes in female and male mice associated with changes in circulating levels of many glycoproteins. Both receptors rise and fall in response to progesterone during pregnancy. Thirty percent of Asgr2(-/-) and 65% of Mrc1(-/ )Asgr2(-/-) mice are unable to initiate parturition at the end of pregnancy, whereas Mrc1(-/-) mice initiate normally. Twenty five percent of Mrc1(-/-)Asgr2( /-) male mice develop priapism when mating due to thrombosis of the penile vein, but neither Mrc1(-/-) nor Asgr2(-/-) mice do so. The half-life for luteinizing hormone (LH) clearance increases in Mrc1(-/-) and Mrc1(-/-)Asgr2(-/-) mice but not in Asgr2(-/-) mice; however, LH and testosterone are elevated in all three knockouts. The ManR clears LH thus regulating testosterone production, whereas the ASGR appears to mediate clearance of an unidentified glycoprotein that increases LH levels. More than 40 circulating glycoproteins are elevated >3.0 fold in pregnant Mrc1(-/-)Asgr2(-/-) mice. Pregnancy-specific glycoprotein 23, undetectable in WT mice (<50 ng/ml plasma), reaches levels of 1-10 mg/ml in the plasma of Mrc1(-/-)Asgr2(-/-) and Asgr2(-/-) mice, indicating it is cleared by the ASGR. Elevation of multiple coagulation factors in Mrc1(-/-)Asgr2(-/-) mice may account for priapism seen in males. These male and female phenotypic changes underscore the key roles of the ManR and ASGR in controlling circulating levels of numerous glycoproteins critical for regulating reproductive hormones and blood coagulation. PMID- 27405761 TI - Conservation and Divergence in Nucleotide Excision Repair Lesion Recognition. AB - Nucleotide excision repair is an important and highly conserved DNA repair mechanism with an exceptionally large range of chemically and structurally unrelated targets. Lesion verification is believed to be achieved by the helicases UvrB and XPD in the prokaryotic and eukaryotic processes, respectively. Using single molecule atomic force microscopy analyses, we demonstrate that UvrB and XPD are able to load onto DNA and pursue lesion verification in the absence of the initial lesion detection proteins. Interestingly, our studies show different lesion recognition strategies for the two functionally homologous helicases, as apparent from their distinct DNA strand preferences, which can be rationalized from the different structural features and interactions with other nucleotide excision repair protein factors of the two enzymes. PMID- 27405762 TI - Substrate Ubiquitination Controls the Unfolding Ability of the Proteasome. AB - In eukaryotic cells, proteins are targeted to the proteasome for degradation by polyubiquitination. These proteins bind to ubiquitin receptors, are engaged and unfolded by proteasomal ATPases, and are processively degraded. The factors determining to what extent the proteasome can successfully unfold and degrade a substrate are still poorly understood. We find that the architecture of polyubiquitin chains attached to a substrate affects the ability of the proteasome to unfold and degrade the substrate, with K48- or mixed-linkage chains leading to greater processivity than K63-linked chains. Ubiquitin-independent targeting of substrates to the proteasome gave substantially lower processivity of degradation than ubiquitin-dependent targeting. Thus, even though ubiquitin chains are removed early in degradation, during substrate engagement, remarkably they dramatically affect the later unfolding of a protein domain. Our work supports a model in which a polyubiquitin chain associated with a substrate switches the proteasome into an activated state that persists throughout the degradation process. PMID- 27405763 TI - Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy. AB - hsc-70 (HSPA8) is a cytosolic molecular chaperone, which plays a central role in cellular proteostasis, including quality control during protein refolding and regulation of protein degradation. hsc-70 is pivotal to the process of macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy. The latter requires hsc-70 interaction with negatively charged phosphatidylserine (PS) at the endosomal limiting membrane. Herein, by combining plasmon resonance, NMR spectroscopy, and amino acid mutagenesis, we mapped the C terminus of the hsc 70 LID domain as the structural interface interacting with endosomal PS, and we estimated an hsc-70/PS equilibrium dissociation constant of 4.7 +/- 0.1 MUm. This interaction is specific and involves a total of 4-5 lysine residues. Plasmon resonance and NMR results were further experimentally validated by hsc-70 endosomal binding experiments and endosomal microautophagy assays. The discovery of this previously unknown contact surface for hsc-70 in this work elucidates the mechanism of hsc-70 PS/membrane interaction for cytosolic cargo internalization into endosomes. PMID- 27405764 TI - Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice. AB - Although numerous biological functions of the activating transcription factor 4 (ATF4) have been identified, a direct effect of ATF4 on alcoholic liver steatosis has not been described previously. The aim of our current study is to investigate the role of ATF4 in alcoholic liver steatosis and elucidate the underlying mechanisms. Here, we showed that the expression of ATF4 is induced by ethanol in hepatocytes in vitro and in vivo, and liver-specific ATF4 knock-out mice are resistant to ethanol-induced liver steatosis, associated with stimulated hepatic AMP-activated protein kinase (AMPK) activity. Furthermore, adenovirus-mediated AMPK knockdown significantly reversed the suppressive effects of ATF4 deficiency on ethanol-induced liver steatosis in mice. In addition, ethanol-fed ATF4 knock out mice exhibit AMPK-dependent inhibition of fatty acid synthase and stimulation of carnitine palmitoyltransferase 1 (CPT1) in the liver. Moreover, hepatic Tribbles homolog 3 (TRB3) expression was stimulated by ethanol in an ATF4 dependent manner, and adenovirus-mediated TRB3 knockdown blocked ATF4-dependent ethanol-induced AMPK inhibition and triglyceride accumulation in AML-12 cells. Finally, TRB3 directly interacted with AMPK to suppress its phosphorylation. Taken together, these results identify the ATF4-TRB3-AMPK axis as a novel pathway responsible for ethanol-induced liver steatosis. PMID- 27405766 TI - Dehydrated Basella alba Fruit Juice as a Novel Natural Colorant: Pigment Stability, In Vivo Food Safety Evaluation and Anti-Inflammatory Mechanism Characterization. AB - Flesh of Basella alba L. mature fruits bearing deep-violet juice provides a novel and potential source of natural colorant. To minimize the pigment purification process and warrant safety acceptability, B. alba colorant powder (BACP) was prepared using mature fruits through a practical batch preparation and subjected to fundamental pigment characterization, food safety assessment and bio-function evaluation. Yield of the dehydrated B. alba colorant powder (BACP) was 37 g/kg fresh fruits. Reconstituted aqueous solution of the BACP exhibited an identical visible spectrum (400-700 nm) as that of fresh juice. Color of the solution (absorbance at 540 nm) was stable in a broad pH ranged from 3 to 8 and enhanced by co-presence of calcium and magnesium ions, while was rapidly bleached by ferrous and ferric ions. For in vivo food safety evaluation, ICR mice were daily gavage administered with BACP up to 1000 mg/kg body weight for 28 days. Organ weight determination, serum biochemical analysis and histopathological examination of hearts, livers, lungs and kidneys revealed no obvious health hazard. In vitro anti-inflammatory activity of BACP was characterized in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. BACP exerted potent anti inflammatory activity by down-regulation of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), TNF-alpha, IL-1beta, IL-6 and IL-12 and the blockage of IkappaB kinase (IKK)/IkappaB/nuclear factor-kappa B (NFkappaB) activation cascade. These results supported that BACP may serve as a beneficial alternative of natural food colorant. PMID- 27405765 TI - CAT7 and cat7l Long Non-coding RNAs Tune Polycomb Repressive Complex 1 Function during Human and Zebrafish Development. AB - The essential functions of polycomb repressive complex 1 (PRC1) in development and gene silencing are thought to involve long non-coding RNAs (lncRNAs), but few specific lncRNAs that guide PRC1 activity are known. We screened for lncRNAs, which co-precipitate with PRC1 from chromatin and found candidates that impact polycomb group protein (PcG)-regulated gene expression in vivo A novel lncRNA from this screen, CAT7, regulates expression and polycomb group binding at the MNX1 locus during early neuronal differentiation. CAT7 contains a unique tandem repeat domain that shares high sequence similarity to a non-syntenic zebrafish analog, cat7l Defects caused by interference of cat7l RNA during zebrafish embryogenesis were rescued by human CAT7 RNA, enhanced by interference of a PRC1 component, and suppressed by interference of a known PRC1 target gene, demonstrating cat7l genetically interacts with a PRC1. We propose a model whereby PRC1 acts in concert with specific lncRNAs and that CAT7/cat7l represents convergent lncRNAs that independently evolved to tune PRC1 repression at individual loci. PMID- 27405768 TI - New biomarkers and therapeutics can be discovered during COPD-lung cancer transition. PMID- 27405767 TI - 'Nature or nurture': survival rate, oviposition interval, and possible gonotrophic discordance among South East Asian anophelines. AB - BACKGROUND: Mosquito survival, oviposition interval and gonotrophic concordance are important determinants of vectorial capacity. These may vary between species or within a single species depending on the environment. They may be estimated by examination of the ovaries of host-seeking mosquitoes. METHODS: Landing collections, Furvela tent-trap and CDC light-trap collections were undertaken sequentially in four locations in Cambodia between February 2012 and December 2013 and samples from the collected mosquitoes were dissected to determine parity, sac stage (indicative of time spent prior to returning to feed) and egg stage. RESULTS: A total of 27,876 Anopheles from 15 species or species groups were collected in the four locations and 2883 specimens were dissected. Both the density and predominant species collected varied according to location and trapping method. Five species were dissected in sufficient numbers to allow comparisons between locations. Estimated oviposition interval differed markedly between species but less within species among different locations. Anopheles aconitus had the shortest cycle, which was 3.17 days (95 % CI 3-3.64), and Anopheles barbirostris had the longest cycle, which took four days (95 % CI 3.29 4). Anopheles minimus had a higher sac rate in weeks leading up to a full moon but there was apparently little effect of moon phase on Anopheles dirus. Despite the fact that many of the species occurred at very low densities, there was no evidence of gonotrophic dissociation in any of them, even during sustained hot, dry periods. The principal Cambodian malaria vector, An. dirus, was only common in one location where it was collected in miniature light-traps inside houses. It did not appear to have an exceptional survival rate (as judged by the low average parous rate) or oviposition cycle. CONCLUSIONS: Differences in the oviposition interval were more pronounced among species within locations than within species among ecologically diverse locations. A nationwide survey using CDC light-traps for the collection of An. dirus inside houses may help in determining patterns of malaria transmission in Cambodia. PMID- 27405769 TI - Octreotide in a Critically Ill Extremely Preterm Infant With Perforated Necrotizing Enterocolitis. AB - Necrotizing enterocolitis (NEC) is the most severe gastrointestinal complication of prematurity. Surgery, either peritoneal drainage placement or laparotomy with resection of the intestinal necrotic tracts, is the definitive treatment of perforated NEC; however, when clinical conditions contraindicate surgical approaches, little is known about medical treatments adjuvant or alternative to surgery. Octreotide is a synthetic somatostatin analog that inhibits pancreatic secretion and leads to splanchnic vasoconstriction. In preterm neonates, it is mainly used off-label for chylothorax and congenital hyperinsulinism, whereas gastrointestinal indications are limited. We describe the case of a critically ill extremely low birth weight infant with perforated NEC, who had unsuccessfully undergone peritoneal drainage placement and laparotomy. Her unstable condition contraindicated a further laparotomy, thus off-label treatment with octreotide was attempted. No adverse events occurred. The infant's condition gradually improved and progressive reduction of peritoneal outputs and successful resolution of pneumoperitoneum were achieved, with no relapse after octreotide discontinuation. PMID- 27405770 TI - Diagnosis, Epidemiology, and Management of Hypertension in Children. AB - National guidelines for the diagnosis and management of hypertension in children have been available for nearly 40 years. Unfortunately, knowledge and recognition of the problem by clinicians remain poor. Prevalence estimates are highly variable because of differing standards, populations, and blood pressure (BP) measurement techniques. Estimates in the United States range from 0.3% to 4.5%. Risk factors for primary hypertension include overweight and obesity, male sex, older age, high sodium intake, and African American or Latino ancestry. Data relating hypertension in childhood to later cardiovascular events is currently lacking. It is known that BP in childhood is highly predictive of BP in adulthood. Compelling data about target organ damage is available, including the association of hypertension with left ventricular hypertrophy, carotid-intima media thickness, and microalbuminuria. Guidelines from both the United States and Europe include detailed recommendations for diagnosis and management. Diagnostic standards are based on clinic readings, ambulatory BP monitoring is useful in confirming diagnosis of hypertension and identifying white-coat hypertension, masked hypertension, and secondary hypertension, as well as monitoring response to therapy. Research priorities include the need for reliable prevalence estimates based on diverse populations and data about the long-term impact of childhood hypertension on cardiovascular morbidity and mortality. Priorities to improve clinical practice include more education among clinicians about diagnosis and management, clinical decision support to aid in diagnosis, and routine use of ambulatory BP monitoring to aid in diagnosis and to monitor response to treatment. PMID- 27405771 TI - Racial and Ethnic Differences in Breastfeeding. AB - OBJECTIVES: Breastfeeding rates differ among racial/ethnic groups in the United States. Our aim was to test whether racial/ethnic disparities in demographic characteristics, hospital use of infant formula, and family history of breastfeeding mediated racial/ethnic gaps in breastfeeding outcomes. METHODS: We analyzed data from the Community and Child Health Network study (N = 1636). Breastfeeding initiation, postnatal intent to breastfeed, and breastfeeding duration were assessed postpartum. Hierarchical linear modeling was used to estimate relative odds of breastfeeding initiation, postnatal intent, and duration among racial/ethnic groups and to test the candidate mediators of maternal age, income, household composition, employment, marital status, postpartum depression, preterm birth, smoking, belief that "breast is best," family history of breastfeeding, in-hospital formula introduction, and WIC participation. RESULTS: Spanish-speaking Hispanic mothers were most likely to initiate (91%), intend (92%), and maintain (mean duration, 17.1 weeks) breastfeeding, followed by English-speaking Hispanic mothers (initiation 90%, intent 88%; mean duration, 10.4 weeks) and white mothers (initiation 78%, intent 77%; mean duration, 16.5 weeks); black mothers were least likely to initiate (61%), intend (57%), and maintain breastfeeding (mean duration, 6.4 weeks). Demographic variables fully mediated disparities between black and white mothers in intent and initiation, whereas demographic characteristics and in-hospital formula feeding fully mediated breastfeeding duration. Family breastfeeding history and demographic characteristics helped explain the higher breastfeeding rates of Hispanic mothers relative to white and black mothers. CONCLUSIONS: Hospitals and policy makers should limit in-hospital formula feeding and consider family history of breastfeeding and demographic characteristics to reduce racial/ethnic breastfeeding disparities. PMID- 27405773 TI - Do we feel the same level of guilt about the wrongdoings of close ones and distant ones? The mediating role of behavioural control. AB - Understanding whether and why individuals' emotional responses are different to the same behaviour performed by different others is important for understanding phenomena in social interaction. Given that there is no relevant research in Eastern culture testing such issues, the present research including two studies was conducted with Chinese samples and investigated whether Easterners experience more vicarious guilt about close ones' immoral behaviours than distant ones' immoral behaviours and the underlying mechanism of the effect. Study 1 showed that people felt more guilty when recalling close ones' misdeeds than distant ones' misdeeds. Study 2 replicated the findings of Study 1 using the scenario method and demonstrated that behavioural control partially mediated the effect of relationship closeness on vicarious guilt, that is, people reported more behavioural control over close ones' immoral behaviours, which in turn resulted in more vicarious guilt. Implications for social interaction and directions for future research are discussed. PMID- 27405772 TI - Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation. AB - The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 +/- 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 +/- 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 +/- 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ?. PMID- 27405774 TI - Severe proarrhythmic potential of risperidone compared to quetiapine in an experimental whole-heart model of proarrhythmia. AB - In several case reports, proarrhythmic effects of antipsychotic drugs have been reported. The aim of the present study was to investigate if application of risperidone or quetiapine has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In 24 isolated rabbit hearts, risperidone (5 and 10 MUM, n = 12) or quetiapine (5 and 10 MUM, n = 12) was infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of risperidone as compared with baseline (5 MUM: +29 ms, 10 MUM: +35 ms, p < 0.01) accompanied by an increase of action potential duration. Administration of risperidone also significantly increased spatial dispersion of repolarization (5 MUM: +16 ms, 4 MUM: +19 ms; p < 0.05) as well as temporal dispersion of repolarization. Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 8 of 12 hearts and polymorphic ventricular tachycardia resembling torsade de pointes in 6 of 12 hearts (10 MUM, 49 episodes). The results were compared with hearts treated with quetiapine (5 and 10 MUM). Quetiapine led to an increase in QT interval (5 MUM: +10 ms; 10 MUM: +28 ms; p < 0.05) and a similar increase of APD90. However, treatment with quetiapine did not result in significant alterations of spatial and temporal dispersion of repolarization. No ventricular arrhythmias were observed in this group. In the present study, quetiapine demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, risperidone led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization. PMID- 27405775 TI - Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations. AB - The calculations of NMR properties of molecules using quantum chemical methods have deeply impacted several branches of organic chemistry. They are particularly important in structural or stereochemical assignments of organic compounds, with implications in total synthesis, stereoselective reactions, and natural products chemistry. In studying the evolution of the strategies developed to support (or reject) a structural proposal, it becomes clear that the most effective and accurate ones involve sophisticated procedures to correlate experimental and computational data. Owing to their relatively high mathematical complexity, such calculations (CP3, DP4, ANN-PRA) are often carried out using additional computational resources provided by the authors (such as applets or Excel files). This Minireview will cover the state-of-the-art of these toolboxes in the assignment of organic molecules, including mathematical definitions, updates, and discussion of relevant examples. PMID- 27405776 TI - A primer on pituitary injury for the obstetrician gynecologist: Simmond's disease, Sheehan's Syndrome, traumatic injury, Dahan's Syndrome, pituitary apoplexy and lymphocytic hypophysitis. AB - The pituitary gland plays a critical role in reproduction. In response to the hypothalamus the anterior pituitary secretes prolactin, thyroid-stimulating hormone, adreno-corticotropic hormone, follicle-stimulating hormone, luteinizing hormone and growth hormone. Dysregulation in these hormones often lead to reproductive failure. Multiple mechanisms of pituitary injury exist. Simmond's disease is atrophy or destruction of the anterior lobe of the pituitary gland resulting in hypopituitarism. Sheehan's syndrome is post-partum pituitary injury due to massive hemorrhage. Traumatic injury resulting in hemorrhage in a non pregnancy state can also cause partial or complete pituitary failure. Dahan's syndrome is pituitary injury due to severe vasospasm, without significant hemorrhage. Pituitary apoplexy is infarction of a pituitary adenoma and intra mass hemorrhage with result injury to hormone production by the gland. Lymphocytic infiltration is the most common cause of hypophysitis and the mechanism is often unknown, although it may be autoimmune-related. The mechanism and treatments of each of these pathologies will be discussed in a context of reproduction. PMID- 27405777 TI - Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers. AB - Overcoming the silencing of the fetal gamma-globin gene has been a long-standing goal in the treatment of sickle cell disease (SCD). The major transcriptional enhancer of the beta-globin locus, called the locus control region (LCR), dynamically interacts with the developmental stage-appropriate beta-type globin genes via chromatin looping, a process requiring the protein Ldb1. In adult erythroid cells, the LCR can be redirected from the adult beta- to the fetal gamma-globin promoter by tethering Ldb1 to the human gamma-globin promoter with custom-designed zinc finger (ZF) proteins (ZF-Ldb1), leading to reactivation of gamma-globin gene expression. To compare this approach to pharmacologic reactivation of fetal hemoglobin (HbF), hematopoietic cells from patients with SCD were treated with a lentivirus expressing the ZF-Ldb1 or with chemical HbF inducers. The HbF increase in cells treated with ZF-Ldb1 was more than double that observed with decitabine and pomalidomide; butyrate had an intermediate effect whereas tranylcypromine and hydroxyurea showed relatively low HbF reactivation. ZF-Ldb1 showed comparatively little toxicity, and reduced sickle hemoglobin (HbS) synthesis as well as sickling of SCD erythroid cells under hypoxic conditions. The efficacy and low cytotoxicity of lentiviral-mediated ZF Ldb1 gene transfer compared with the drug regimens support its therapeutic potential for the treatment of SCD. PMID- 27405778 TI - Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells. AB - Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a key regulatory function in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion. Previous studies documented metabolic reprogramming in stored red blood cells (RBCs) and oxidation of GAPDH at functional residues upon exposure to pro-oxidants diamide and H2O2 Here we hypothesize that routine storage of erythrocyte concentrates promotes metabolic modulation of stored RBCs by targeting functional thiol residues of GAPDH. Progressive increases in PPP/glycolysis ratios were determined via metabolic flux analysis after spiking (13)C1,2,3-glucose in erythrocyte concentrates stored in Additive Solution-3 under blood bank conditions for up to 42 days. Proteomics analyses revealed a storage-dependent oxidation of GAPDH at functional Cys152, 156, 247, and His179. Activity loss by oxidation occurred with increasing storage duration and was progressively irreversible. Irreversibly oxidized GAPDH accumulated in stored erythrocyte membranes and supernatants through storage day 42. By combining state-of-the-art ultra-high-pressure liquid chromatography-mass spectrometry metabolic flux analysis with redox and switch tag proteomics, we identify for the first time ex vivo functionally relevant reversible and irreversible (sulfinic acid; Cys to dehydroalanine) oxidations of GAPDH without exogenous supplementation of excess pro-oxidant compounds in clinically relevant blood products. Oxidative and metabolic lesions, exacerbated by storage under hyperoxic conditions, were ameliorated by hypoxic storage. Storage-dependent reversible oxidation of GAPDH represents a mechanistic adaptation in stored erythrocytes to promote PPP activation and generate reducing equivalents. Removal of irreversibly oxidized, functionally compromised GAPDH identifies enhanced vesiculation as a self-protective mechanism in ex vivo aging erythrocytes. PMID- 27405779 TI - V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog A Synthetic Modified mRNA Drives Reprogramming of Human Pancreatic Duct-Derived Cells Into Insulin Secreting Cells. AB - : : beta-Cell replacement therapy represents the most promising approach to restore beta-cell mass and glucose homeostasis in patients with type 1 diabetes. Safety and ethical issues associated with pluripotent stem cells stimulated the search for adult progenitor cells with endocrine differentiation capacities. We have already described a model for expansion and differentiation of human pancreatic duct-derived cells (HDDCs) into insulin-producing cells. Here we show an innovative and robust in vitro system for large-scale production of beta-like cells from HDDCs using a nonintegrative RNA-based reprogramming technique. Synthetic modified RNAs for pancreatic transcription factors (pancreatic duodenal homeobox 1, neurogenin3, and V-Maf musculoaponeurotic fibrosarcoma oncogene homolog A [MAFA]) were manufactured and daily transfected in HDDCs without strongly affecting immune response and cell viability. MAFA overexpression was efficient and sufficient to induce beta-cell differentiation of HDDCs, which acquired a broad repertoire of mature beta-cell markers while downregulating characteristic epithelial-mesenchymal transition markers. Within 7 days, MAFA reprogrammed HDDC populations contained 37% insulin-positive cells and a proportion of endocrine cells expressing somatostatin and pancreatic polypeptide. Ultrastructure analysis of differentiated HDDCs showed both immature and mature insulin granules with light-backscattering properties. Furthermore, in vitro HDDC derived beta cells (called beta-HDDCs) secreted human insulin and C-peptide in response to glucose, KCl, 3-isobutyl-1-methylxanthine, and tolbutamide stimulation. Transplantation of beta-HDDCs into diabetic SCID-beige mice confirmed their functional glucose-responsive insulin secretion and their capacity to mitigate hyperglycemia. Our data describe a new, reliable, and fast procedure in adult human pancreatic cells to generate clinically relevant amounts of new beta cells with potential to reverse diabetes. SIGNIFICANCE: beta-Cell replacement therapy represents the most promising approach to restore glucose homeostasis in patients with type 1 diabetes. This study shows an innovative and robust in vitro system for large-scale production of beta-like cells from human pancreatic duct-derived cells (HDDCs) using a nonintegrative RNA-based reprogramming technique. V-Maf musculoaponeurotic fibrosarcoma oncogene homolog A overexpression was efficient and sufficient to induce beta-cell differentiation and insulin secretion from HDDCs in response to glucose stimulation, allowing the cells to mitigate hyperglycemia in diabetic SCID-beige mice. The data describe a new, reliable, and fast procedure in adult human pancreatic cells to generate clinically relevant amounts of new beta cells with the potential to reverse diabetes. PMID- 27405780 TI - Antifibrotic Activity of Human Placental Amnion Membrane-Derived CD34+ Mesenchymal Stem/Progenitor Cell Transplantation in Mice With Thioacetamide Induced Liver Injury. AB - : : Liver fibrosis represents the end stage of chronic liver inflammatory diseases and is defined by the abnormal accumulation of extracellular matrix in the liver. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Liver transplantation has been the most effective treatment for these diseases, but the procedure is limited by the shortage of suitable donors. Mesenchymal stromal cells (MSCs) have shown great potential in the treatment of chronic inflammatory diseases associated with fibrosis. This study aimed to evaluate the therapeutic effect of MSC-based cell transplantation as an alternative treatment for liver fibrosis. A CD34-positive subpopulation of human placental amnion membrane-derived stem/progenitor cells (CD34+ AMSPCs) was isolated through the depletion of CD34-negative stromal fibroblasts (CD34- AMSFCs) facilitated by CD34 fluorescence-activated cell sorting, enriched and expanded ex vivo. These cells express pluripotency markers and demonstrate multidirectional differentiation potentials. Comparative analysis was made between CD34+ AMSPCs and CD34- AMSFCs in terms of the expressions of stemness surface markers, embryonic surface antigens, and multilineage differentiation potentials. A mouse model of liver fibrosis was established by thioacetamide (TAA) administration. When injected into the spleen of TAA-injured mice, human placental amnion membrane-derived MSCs (hAM-MSCs) can engraft into the injury site, ameliorate liver fibrosis, and restore liver function, as shown by pathological and blood biochemical analysis and downregulated gene expressions associated with liver damage. CD34+ AMSPCs represent a more primitive subset of hAM-MSCs and could be a suitable candidate with a potentially better safety profile for cell-based therapy in treatment of liver diseases associated with fibrosis. SIGNIFICANCE: In this study, a CD34+ subpopulation of stem/progenitor cells derived from neonatal placental amnion membrane, denoted as CD34+ AMSPCs, were identified, enriched, and characterized. These cells are highly proliferative, express mesenchymal stromal cells and pluripotent stem cell markers, and demonstrate multidirectional differentiation potentials, indicating their promising application in clinical regenerative therapies. CD34+ AMSPC transplantation ameliorated liver fibrosis in mice with drug-induced liver injury. These cells represent a potential therapeutic agent for treating liver diseases associated with fibrosis. PMID- 27405781 TI - First Proposal of Minimum Information About a Cellular Assay for Regenerative Medicine. AB - : : Advances in stem cell research have triggered scores of studies in regenerative medicine in a large number of institutions and companies around the world. However, reproducibility and data exchange among laboratories or cell banks are constrained by the lack of a standardized format for experiments. To enhance information flow in stem cell and derivative cell research, here we propose a minimum information standard to describe cellular assay data to facilitate practical regenerative medicine. Based on the existing Minimum Information About a Cellular Assay, we developed Minimum Information About a Cellular Assay for Regenerative Medicine (MIACARM), which allows for the description of advanced cellular experiments with defined taxonomy of human cell types. By using controlled terms, such as ontologies, MIACARM will provide a platform for cellular assay data exchange among cell banks or registries that have been established at more than 20 sites in the world. SIGNIFICANCE: Currently, there are more than 20 human cell information storage sites around the world. However, reproducibility and data exchange among different laboratories or cell information providers are usually inadequate or nonexistent because of the lack of a standardized format for experiments. This study, which is the fruit of collaborative work by scientists at stem cell banks and cellular information registries worldwide, including those in the U.S., the U.K., Europe, and Japan, proposes new minimum information guidelines, Minimum Information About a Cellular Assay for Regenerative Medicine (MIACARM), for cellular assay data deposition. MIACARM is intended to promote data exchange and facilitation of practical regenerative medicine. PMID- 27405782 TI - Complications of Kirschner Wire Use in Open Reduction and Internal Fixation of Calcaneal Fractures. AB - The most important goal of surgical management of displaced intra-articular calcaneal fractures is anatomic correction. This reduction is usually stabilized using plate and screw osteosynthesis. In addition, Kirschner wires (K-wires) can be used to maintain the surgical reduction or stability of the construct. In the present study, we evaluated the frequency and type of use of additional K-wires and subsequent migration in the surgical management of displaced intra-articular calcaneal fractures. The data from 279 patients treated surgically from January 1, 2000 to December 31, 2014 in a level 1 trauma center using an extended lateral approach were analyzed after 1 year of follow-up. All postoperative radiographic images were reviewed to identify the cases in which K-wires were used. Data on the number and type of K-wires used, K-wire location, and K-wire migration found on follow-up imaging studies were collected. Of the 279 patients, 69 K-wires had been used in 49 (18%) patients. A total of 25 (36%) lost (buried), 38 (55%) bent, and 6 (9%) unmodified straight K-wires had been placed. Overall, in 4 (5.8%) of 69 K-wires, secondary dislocation was seen. One (4%) of the lost, 3 (50%) of the unmodified, and none of the bent K-wires showed secondary dislocation. K-wire migration was seen in 5.8% of the cases. None of the bent K-wires and only 1 of the lost K-wires had migrated in the present study. These 2 techniques are preferred when using K-wire fixation in the treatment of displaced intra articular calcaneal fractures. The use of unmodified straight K-wires should be discouraged. PMID- 27405783 TI - Research of the spatial-temporal gait parameters and pressure characteristic in spastic diplegia children. AB - PURPOSE: Spastic diplegia is the most common form of cerebral palsy. It presents with symmetric involvement of the lower limbs and upper limbs. Children with spastic diplegia frequently experience problems with motor control, spasticity, and balance which lead to gait abnormalities. The aim of this study is twofold. Firstly, to determine the differences in spatial-temporal gait parameters and magnitude of plantar pressure distribution between children with spastic diplegia (CP) and typical children. Secondly, to compare and evaluate main changes of plantar pressure and spatial-temporal gait parameters instead of data between spastic diplegia children with prescribed ankle - solid foot orthosis (AFOs) and without using AFOs. METHODS: The evaluation was carried out on 20 spastic diplegia children and 10 agematched children as a control group aged 6-15 years. Twenty children with spastic diplegia CP were divided into two groups: ten subjects with prescribed AFOs and ten subjects without use of assistive device. Patients used the AFOs orthosis for one year. Measurements included in-shoe plantar pressure distribution and spatial-temporal gait parameters. RESULTS: Spatial-temporal gait parameters showed meaningful difference between study groups in velocity, stride length, step length and cadence ( p < 0.05). However no significant differences between patients with and without AFOs were found ( p > 0.05). Significant differences between typical and spastic diplegia children with AFOs were observed in the magnitude of plantar pressure under the toes, the metatarsal heads, the medial arch, and the heel ( p < 0.05). For typical subjects, the highest pressure amplitudes were found under the heel and the metatarsal heads, while the lowest pressure distribution was under the medial arch. In CP patients the lateral arch was strongly unloaded. The peak pressure under heel was shifted inside. CONCLUSIONS: Collected data and calculated scores present a state of the gait in test groups, showed the difference and could be valuable for physicians in decision making by choosing qualitative therapy. Furthermore, it allows predicting probability of further possible changes in gait of spastic diplegia patients with AFOs and without it. In conclusion, our current results showed that the use of AFOs, prescribed on a clinical basis by doctors improves gait patterns and gait stability in children with spastic cerebral palsy. PMID- 27405784 TI - Piloting staff education in Australia to reduce falls in older hospital patients experiencing delirium. AB - This study piloted a hospital-based delirium and falls education program to investigate the impacts on staff knowledge and practice plus patient falls. On a medical ward, staff knowledge was compared before and after education sessions. Other data - collected a day before and after program implementation - addressed documentation of patients' delirium and evidence of compliance with falls risk minimization protocols. These data, and numbers of patient falls, were compared before and after program implementation. Almost all ward staff members participated in education sessions (7 doctors, 7 allied health practitioners, and 45 nurses) and knowledge was significantly improved in the 22 who completed surveys both before and after session attendance. Patients assessed as having delirium (5 before implementation, 4 afterwards) were all documented as either confused or delirious. Small changes eventuated in adherence with falls risk management protocols for confused patients and the number of falls decreased. The program merits a stronger emphasis on staff activities relating to the detection, documentation, and management of delirium to inter-professional roles and communication. Evidence of practice enhancement from program implementation should precede rigorous testing of impacts upon falls. PMID- 27405785 TI - Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life. AB - Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naive and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guidelines. PMID- 27405786 TI - Exciton Relaxation Dynamics in Photo-Excited CsPbI3 Perovskite Nanocrystals. AB - The exciton relaxation process of CsPbI3 perovskite nanocrystals (NCs) has been investigated by using transient absorption (TA) spectroscopy. The hot exciton relaxation process is confirmed to exist in the CsPbI3 NCs, through comparing the TA data of CsPbI3 NCs in low and high energy excitonic states. In addition, the Auger recombination and intrinsic decay paths also participate in the relaxation process of CsPbI3 NCs, even the number of exciton per NC is estimated to be less than 1. Excitation intensity-dependent TA data further confirms the existence of Auger recombination. Meanwhile, the spectral data also confirms that the weight of hot exciton also increase together with that of Auger recombination at high excitation intensity when CsPbI3 NCs in high energy excitonic states. PMID- 27405787 TI - Is the Juice Worth the Squeeze? Costs and Benefits of Multiple Human Annotators for Clinical Text De-identification. AB - BACKGROUND: Clinical text contains valuable information but must be de-identified before it can be used for secondary purposes. Accurate annotation of personally identifiable information (PII) is essential to the development of automated de identification systems and to manual redaction of PII. Yet the accuracy of annotations may vary considerably across individual annotators and annotation is costly. As such, the marginal benefit of incorporating additional annotators has not been well characterized. OBJECTIVES: This study models the costs and benefits of incorporating increasing numbers of independent human annotators to identify the instances of PII in a corpus. We used a corpus with gold standard annotations to evaluate the performance of teams of annotators of increasing size. METHODS: Four annotators independently identified PII in a 100-document corpus consisting of randomly selected clinical notes from Family Practice clinics in a large integrated health care system. These annotations were pooled and validated to generate a gold standard corpus for evaluation. RESULTS: Recall rates for all PII types ranged from 0.90 to 0.98 for individual annotators to 0.998 to 1.0 for teams of three, when meas-ured against the gold standard. Median cost per PII instance discovered during corpus annotation ranged from $ 0.71 for an individual annotator to $ 377 for annotations discovered only by a fourth annotator. CONCLUSIONS: Incorporating a second annotator into a PII annotation process reduces unredacted PII and improves the quality of annotations to 0.99 recall, yielding clear benefit at reasonable cost; the cost advantages of annotation teams larger than two diminish rapidly. PMID- 27405788 TI - Magnetic Tunnel Junction Based Long-Term Short-Term Stochastic Synapse for a Spiking Neural Network with On-Chip STDP Learning. AB - Spiking Neural Networks (SNNs) have emerged as a powerful neuromorphic computing paradigm to carry out classification and recognition tasks. Nevertheless, the general purpose computing platforms and the custom hardware architectures implemented using standard CMOS technology, have been unable to rival the power efficiency of the human brain. Hence, there is a need for novel nanoelectronic devices that can efficiently model the neurons and synapses constituting an SNN. In this work, we propose a heterostructure composed of a Magnetic Tunnel Junction (MTJ) and a heavy metal as a stochastic binary synapse. Synaptic plasticity is achieved by the stochastic switching of the MTJ conductance states, based on the temporal correlation between the spiking activities of the interconnecting neurons. Additionally, we present a significance driven long-term short-term stochastic synapse comprising two unique binary synaptic elements, in order to improve the synaptic learning efficiency. We demonstrate the efficacy of the proposed synaptic configurations and the stochastic learning algorithm on an SNN trained to classify handwritten digits from the MNIST dataset, using a device to system-level simulation framework. The power efficiency of the proposed neuromorphic system stems from the ultra-low programming energy of the spintronic synapses. PMID- 27405789 TI - Cell morphologic changes and PCNA expression within craniofacial sutures during monkey Class III treatment. AB - OBJECTIVES: To evaluate and compare the cellular morphologic changes and proliferating cell nuclear antigen (PCNA) expression within craniofacial sutures in growing Rhesus monkeys treated with a Class III functional appliance. MATERIALS AND METHODS: Six Rhesus monkeys in the mixed dentition stage were divided into three groups: a 45-day experimental group, a 90-day experimental group, and a control group. Monkeys in the experimental groups were fitted with a Class III magnetic twin-block appliance. Cellular changes in six craniofacial sutures-the zygomaticomaxillary, zygomaticotemporal, transverse palatine, pterygopalatine, zygomaticofrontal, and frontomaxillary sutures were qualitatively and quantitatively evaluated by means of histomorphologic analysis, TEM, and immunohistochemical test of PCNA. RESULTS: Obvious and altered bone remodeling combined with bone deposition and resorption was present in craniofacial sutures in the experimental groups. Increased activity of enlarged fibroblasts with abundant organelles was revealed. PCNA expression increased in the 45-day group compared with the control group, followed by the 90-day group. The highest percentage of PCNA-positive cells was found in the pterygopalatine suture in the 45-day group and the zygomaticomaxillary suture in the 90-day group. CONCLUSIONS: The pterygopalatine and zygomaticomaxillary sutures are more active among the craniofacial sutures in the craniofacial complex remodeling during Class III treatment. The magnetic twin-block appliance effectively promoted suture remodeling by enhancing the activity and proliferation of osteoblasts, osteoclasts, and fibroblasts, especially in the early phase. PMID- 27405790 TI - Is there yet a role for internal iliac artery ligation in obstetric hemorrhage with the current gain in popularity of other uterus sparing techniques? AB - PURPOSE: To evaluate the success rates and subsequent fertility outcomes of internal iliac artery ligation (IIAL) in uterine atony (primary ligated and secondary added to other uterus sparing techniques), retroperitoneal hematoma, and placenta adherent abnormalities. MATERIAL AND METHODS: Fifty two women who underwent IIAL for different causes of postpartum hemorrhage were retrospectively evaluated. RESULTS: Among 26 women with intractable uterine atony, 12 had primary, and 14 secondary IIAL, due to ongoing bleeding following the B-Lynch suture or the Bakri balloon tamponade. The success rates were 91% and 71.4% in the primary and secondary IIAL groups, respectively. The success rates of IIAL in 12 women with placental adhesion abnormalities and another 12 with obstetric retroperitoneal hematoma were 75% (9/12) and 83% (10/12) respectively. Nine (17%) hysterectomies were performed after failure of IIAL. Two maternal deaths occurred in our study. The rate of achieving pregnancy was not significantly different between the groups. CONCLUSIONS: Hysterectomy rates might be decreased with the addition of IIAL provided that other uterus sparing techniques; B-Lynch or the Bakri balloon was to fail separately. IIAL can save lives in severe obstetric retroperitoneal hematoma. IIAL does not affect fertility even it is combined with other uterus sparing techniques like the Bakri balloon and B-Lynch suture. PMID- 27405791 TI - Low pasture allowance until late gestation in ewes: behavioural and physiological changes in ewes and lambs from lambing to weaning. AB - Low pasture allowance during gestation affects ewes' BW at parturition, the bond with their lamb, lamb development, and thus also may affect their responses to weaning. The objectives were to determine if native pasture allowance from before conception until late pregnancy affects ewe-lamb behaviours at lambing, ewes' milk yield, lambs' BW, and the behavioural and physiological changes of ewes and lambs at weaning. From 23 days before conception until 122 days of pregnancy, 24 ewes grazed on two different native pasture allowances: high (10 to 12 kg of dry matter (DM)/100 kg of BW per day; HPA treatment; n=12) or low (5 to 8 kg of DM/100 kg of BW per day; LPA treatment; n=12). Thereafter, all ewes grazed on Festuca arundinacea and received rice bran and crude glycerine. Ewes' body condition score (BCS) and BW were recorded during pregnancy and postpartum periods. Milk yield was determined on days 32, 41 and 54 after lambing. Lambs' BW was recorded from birth until 72 days after lambing. Latency from parturition until the ewe licked her lamb, maternal behaviour score (a test that evaluates maternal attachment to the lamb) and latency for lamb to stand up and suckle were determined. The behaviour of the lambs and ewes was recorded before and after weaning (at 65 days). The ewes' serum total protein, albumin and globulin concentrations were measured before and after weaning. The HPA ewes presented greater BW (P<0.005) and BCS (P<0.005) than the LPA ewes during pregnancy and postpartum (P<0.04), and had a greater milk yield than the LPA ewes (P<0.03). Treatments did not influence any behaviour at lambing, lambs' BW, neither the ewes' behavioural and physiological changes at weaning. HPA lambs paced and vocalized more than LPA lambs (P<0.0001). The variation of albumin concentration before and after weaning was greater in the HPA lambs than in the LPA lambs (P<0.0001). In conclusion, although ewes' BW, BCS and milk production were affected by pasture allowance until late pregnancy, this did not affect the behaviours that lead to the establishment of the mother-young bond, nor the ewes' behavioural responses at weaning. Lambs reared by ewes that grazed on low pasture allowance during pregnancy presented fewer behavioural changes and a lower decrease of albumin concentration after weaning. Lambs' BW was not affected by the feeding received by their mothers. PMID- 27405792 TI - Rhodomentones A and B, novel meroterpenoids with unique NMR characteristics from Rhodomyrtus tomentosa. AB - Two novel meroterpenoids, rhodomentones A and B bearing an unprecedented caryophyllene-conjugated oxa-spiro[5.8] tetradecadiene skeleton, were isolated from the leaves of Rhodomyrtus tomentosa. Their structures with unique NMR characteristics were determined by extensive spectroscopic analysis, single crystal X-ray diffraction, quantum molecular calculation, chemical transformation as well as total synthesis. PMID- 27405793 TI - Uranium-Carbene-Imido Metalla-Allenes: Ancillary-Ligand-Controlled cis-/trans Isomerisation and Assessment of trans Influence in the R2 C=U(IV) =NR' Unit (R=Ph2 PNSiMe3 ; R'=CPh3 ). AB - Uranium(IV)-carbene-imido complexes [U(BIPM(TMS) )(NCPh3 )(kappa(2) -N,N'-BIPY)] (2; BIPM(TMS) =C(PPh2 NSiMe3 )2 ; BIPY=2,2-bipyridine) and [U(BIPM(TMS) )(NCPh3 )(DMAP)2 ] (3; DMAP=4-dimethylamino-pyridine) that contain unprecedented, discrete R2 C=U=NR' units are reported. These complexes complete the family of E=U=E (E=CR2 , NR, O) metalla-allenes with feasible first-row hetero-element combinations. Intriguingly, 2 and 3 contain cis- and trans-C=U=N units, respectively, representing rare examples of controllable cis/trans isomerisation in f-block chemistry. This work reveals a clear-cut example of the trans influence in a mid-valent uranium system, and thus a strong preference for the cis isomer, which is computed in a co-ligand-free truncated model-to isolate the electronic trans influence from steric contributions-to be more stable than the trans isomer by approximately 12 kJ mol(-1) with an isomerisation barrier of approximately 14 kJ mol(-1) . PMID- 27405794 TI - Reduction Sensitive Lipid Conjugates of Tenofovir: Synthesis, Stability, and Antiviral Activity. AB - The therapeutic value of numerous small molecules hinges on their ability to permeate the plasma membrane. This is particularly true for tenofovir (TFV), adefovir, and other antiviral nucleosides that demonstrate potent antiviral activity but poor bioavailability. Using TFV as a model substrate, we hybridized two disparate prodrug strategies to afford novel reduction-sensitive lipid conjugates of TFV that exhibit subnanomolar activity toward HIV-1 and are stable in human plasma for more than 24 h with a therapeutic index approaching 30000. These compounds significantly rival the clinically approved formulation of TFV and revitalize the potential of disulfide-bearing prodrugs which have seen limited in vitro and in vivo success since their debut over 20 years ago. We further demonstrate the utility of these conjugates as a tool to indirectly probe the enzymatic hydrolysis of phosphonomonoesters that may further advance the development of other prodrug strategies for nucleosides, peptides, and beyond. PMID- 27405796 TI - Neratinib, A Novel HER2-Targeted Tyrosine Kinase Inhibitor. AB - HER2 gene amplification and receptor overexpression is identified in 20% to 25% of human breast cancers. Use of targeted therapy for HER2-amplified breast cancer has led to improvements in disease-free and overall survival in this subset of patients. Neratinib is an oral pan HER inhibitor, that irreversibly inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR or HER1), HER2, and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is currently being tested in a number of clinical trials for its safety and efficacy in lung cancer, and colorectal, bladder, and breast cancers. In this review we discuss the available phase I, II, and III data for use of neratinib in the metastatic, adjuvant, neoadjuvant, and extended adjuvant settings along with the ongoing clinical trials of neratinib in breast cancer. We also elaborate on the side effect profile of this relatively new drug and provide guidelines for its use in clinical practice. PMID- 27405797 TI - Polarisation-based coincidence event discrimination: an in silico study towards a feasible scheme for Compton-PET. AB - Current positron emission tomography (PET) systems use temporally localised coincidence events discriminated by energy and time-of-flight information. The two annihilation photons are in an entangled polarisation state and, in principle, additional information from the polarisation correlation of photon pairs could be used to improve the accuracy of coincidence classification. In a previous study, we demonstrated that in principle, the polarisation correlation information could be transferred to an angular correlation in the distribution of scattered photon pairs in a planar Compton camera system. In the present study, we model a source-phantom-detector system using Geant4 and we develop a coincidence classification scheme that exploits the angular correlation of scattered annihilation quanta to improve the accuracy of coincidence detection. We find a [Formula: see text] image quality improvement in terms of the peak signal-to-noise ratio when scattered coincidence events are discriminated solely by their angular correlation, thus demonstrating the feasibility of this novel classification scheme. By integrating scatter events (both single-single and single-only) with unscattered coincidence events discriminated using conventional methods, our results suggest that Compton-PET may be a promising candidate for optimal emission tomographic imaging. PMID- 27405795 TI - Phylogenetic incongruence and the evolutionary origins of cardenolide-resistant forms of Na(+) ,K(+) -ATPase in Danaus butterflies. AB - Many distantly related insect species are specialized feeders of cardenolide containing host plants such as milkweed (Asclepias spp.). Previous studies have revealed frequent, parallel substitution of a functionally important amino acid substitution (N122H) in the alpha subunit of Na(+) ,K(+) -ATPase in a number of these species. This substitution facilitates the ability of these insects to feed on their toxic hosts and sequester cardenolides for their own use in defense. Among milkweed butterflies of the genus Danaus, the previously established phylogeny for this group suggests that N122H arose independently and fixed in two distinct lineages. We reevaluate this conclusion by examining Danaus phylogenetic relationships using >400 orthologous gene sequences assembled from transcriptome data. Our results indicate that the three Danaus species known to harbor the N122H substitution are more closely related than previously thought, consistent with a single, common origin for N122H. However, we also find evidence of both incomplete lineage sorting and post-speciation genetic exchange among these butterfly species, raising the possibility of collateral evolution of cardenolide insensitivity in this species group. PMID- 27405798 TI - Intraoperative compliance profiles and regional lung ventilation improve with increasing positive end-expiratory pressure. AB - BACKGROUND: Anaesthesia and mechanical ventilation can lead to impaired lung. Intraoperative positive end-expiratory pressure (PEEP) should prevent intratidal recruitment/derecruitment without causing overdistension. The intratidal compliance profile indicates both unwanted phenomena. We hypothesized that a higher than usual PEEP improves the intratidal compliance and the regional lung ventilation of patients with healthy lungs. METHODS: After ethics approval, 30 adult patients scheduled for limb surgery were investigated at PEEP 5, 7 and 9 cm H2 O during mechanical ventilation. We calculated the dynamic compliance of the respiratory system (CRS ) and the intratidal volume-dependent CRS curve. The CRS curve indicated intratidal recruitment/derecruitment and/or overdistension. Regional ventilation was measured using electrical impedance tomography. RESULTS: At PEEP 5, 7 and 9 cm H2 O, intratidal recruitment/derecruitment was observed in 92%, 84% and 46% (P < 0.05) of the patients respectively. Increasing PEEP was associated with recruitment in the dorsal regions of the lungs (P < 0.001). At PEEP 9 cm H2 O, lung overdistension was indicated in two patients. With PEEP levels up to 9 cm H2 O, no significant effects on haemodynamic variables were found. CONCLUSION: We conclude that in most patients, the often applied PEEP of 5 cm H2 O is insufficient to prevent intratidal recruitment/derecruitment and that few patients show overdistension at high PEEP levels. To establish optimal pressure-volume relationships in the respiratory system, the analysis of the individual intratidal compliance profiles could be a means for individualized perioperative PEEP titration. PMID- 27405799 TI - Reoperative transapical transcatheter aortic valve replacement for central aortic regurgitation. AB - Paravalvular leak-related aortic regurgitation after transcatheter aortic valve replacement (TAVR) is a common complication and is associated with increased short- and long-term mortality. However, the impact of isolated central aortic regurgitation is unknown. We report a case of transapical (TA) TAVR with postprocedural central aortic regurgitation, who returned after two years with progression of regurgitation. A reoperative valve-in-valve TA-TAVR was performed. PMID- 27405800 TI - Gestational Alcohol Exposure and Other Factors Associated With Continued Teenage Drinking. AB - Purpose A longitudinal cohort of adolescents who initiated drinking before age 15 were studied to determine which factors distinguished between early initiators who continued to drink (persisters) from those who stopped drinking (desisters). There were 308 early initiators in the total sample (n = 917); 247 were persisters, and 61 were desisters. Method A stepwise discriminant analysis identified differences between the two groups. Considered risk/protective factors were parenting practices, peer drinking, child and maternal depression, child behavior, prenatal alcohol exposure, home environment, and demographic factors. Results Desistence was significantly related to African American race and more parental strictness. Exposure to >=1 drink/day during pregnancy and high levels of autonomy from parents were significant predictors of persistent drinking. Conclusions Early initiation places adolescents at risk for continued and heavier drinking. Identifying characteristics of those who start early but do or do not continue drinking can inform education programs to better target the most appropriate adolescents. PMID- 27405801 TI - Engaging Teammates in the Promotion of Concussion Help Seeking. AB - Concussion underreporting contributes to the substantial public health burden of concussions from sport. Teammates may be able to play an important role in encouraging injury identification and help seeking. This study assessed whether there was an association between beliefs about the consequences of continued play with a concussion and intentions to engage as a proactive bystander in facilitating or encouraging teammate help seeking for a possible concussion. Participants were 328 (male and female) members of 19 U.S. collegiate contact or collision sports teams. Athletes who believed that there were negative health or performance consequences of continued play with a concussion were significantly more likely than their peers to intend to encourage teammate help seeking, but not more likely to alert a coach or medical personnel. Additionally, athletes who believed that their teammates were more supportive of concussion safety were more likely to intend to engage as proactive bystanders in encouraging teammate help seeking. Exploring how to encourage bystander promotion of concussion safety is an important direction for future programming and evaluation research and may provide an opportunity to improve the effectiveness of concussion education. PMID- 27405802 TI - Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects. AB - During endochondral ossification, chondrocytes embed themselves in a proteoglycan rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20B(fl/fl) mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling. PMID- 27405803 TI - Integrative analysis with ChIP-seq advances the limits of transcript quantification from RNA-seq. AB - RNA-seq is currently the technology of choice for global measurement of transcript abundances in cells. Despite its successes, isoform-level quantification remains difficult because short RNA-seq reads are often compatible with multiple alternatively spliced isoforms. Existing methods rely heavily on uniquely mapping reads, which are not available for numerous isoforms that lack regions of unique sequence. To improve quantification accuracy in such difficult cases, we developed a novel computational method, prior-enhanced RSEM (pRSEM), which uses a complementary data type in addition to RNA-seq data. We found that ChIP-seq data of RNA polymerase II and histone modifications were particularly informative in this approach. In qRT-PCR validations, pRSEM was shown to be superior than competing methods in estimating relative isoform abundances within or across conditions. Data-driven simulations suggested that pRSEM has a greatly decreased false-positive rate at the expense of a small increase in false negative rate. In aggregate, our study demonstrates that pRSEM transforms existing capacity to precisely estimate transcript abundances, especially at the isoform level. PMID- 27405804 TI - Novel features of telomere biology revealed by the absence of telomeric DNA methylation. AB - Cytosine methylation regulates the length and stability of telomeres, which can affect a wide variety of biological features, including cell differentiation, development, or illness. Although it is well established that subtelomeric regions are methylated, the presence of methylated cytosines at telomeres has remained controversial. Here, we have analyzed multiple bisulfite sequencing studies to address the methylation status of Arabidopsis thaliana telomeres. We found that the levels of estimated telomeric DNA methylation varied among studies. Interestingly, we estimated higher levels of telomeric DNA methylation in studies that produced C-rich telomeric strands with lower efficiency. However, these high methylation estimates arose due to experimental limitations of the bisulfite technique. We found a similar phenomenon for mitochondrial DNA: The levels of mitochondrial DNA methylation detected were higher in experiments with lower mitochondrial read production efficiencies. Based on experiments with high telomeric C-rich strand production efficiencies, we concluded that Arabidopsis telomeres are not methylated, which was confirmed by methylation-dependent restriction enzyme analyses. Thus, our studies indicate that telomeres are refractory to de novo DNA methylation by the RNA-directed DNA methylation machinery. This result, together with previously reported data, reveals that subtelomeric DNA methylation controls the homeostasis of telomere length. PMID- 27405805 TI - The use of gabapentin in the management of postoperative pain after total hip arthroplasty: a meta-analysis of randomised controlled trials. AB - BACKGROUND: Pain management after total hip arthroplasty (THA) varies and has been widely studied in recent years. Gabapentin as a third-generation antiepileptic drug that selectively affects the nociceptive process has been used for pain relief after THA. This meta-analysis was conducted to examine the efficacy of gabapentin in THA. METHODS: An electronic-based search was conducted using the following databases: PubMed, EMBASE, Ovid MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL). Randomised controlled trials (RCTs) involving gabapentin and a placebo for THA were included. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Five trials met the inclusion criteria. The cumulative narcotic consumption and the visual analogue scale (VAS) scores at 24 and 48 h postoperatively were used for postoperative pain assessment. There was a significant decrease in morphine consumption at 24 h (P = 0.00). Compared with the control group, the VAS score (at rest) at 48 h was less in the gabapentin group (P = 0.00). CONCLUSION: The administration of gabapentin is effective in decreasing postoperative narcotic consumption and the VAS score. PMID- 27405806 TI - Assessing the completeness of coded and narrative data from the Victorian Emergency Minimum Dataset using injuries sustained during fitness activities as a case study. AB - BACKGROUND: Injury surveillance systems support the ongoing systematic collection, analysis and interpretation of health information vital to the prevention, planning and evaluation of injury prevention strategies. One key measure of the success of such systems is their reliability. Data completeness is a major component of system reliability, and is an indicator of a system's data quality. The Victorian Emergency Minimum Dataset (VEMD) is a state-wide record of injury presentations to emergency departments in Victoria, Australia. For each case, it provides information on the injury cause, place of occurrence, activity at time of injury, body region affected and nature of injury, as well as a free text narrative of the injury event. The aim of this study was to assess the completeness of data in the VEMD using injuries sustained in fitness facilities as a case study. METHODS: Analysis of VEMD coded parent injury variables (nature of injury, injured body region, cause of injury, place where injury occurred, activity at time of injury) and detailed narratives were reviewed for completeness over the ten-year period July 2003 to June 2012, inclusive. Narratives were text analysed manually to determine which items of injury information they contained and compared to the parent injury variables. RESULTS: There were 2936 identified cases related to injuries sustained during fitness activities. Two percent of cases had all coded injury variables unspecified. Overall, 95.8 % of narratives had at least one piece of injury information missing. The nature of injury and body region variables were coded in 92.6 and 96.6 % of cases, yet were only mentioned in 27.1 and 75.4 % of narratives, respectively. The cause variable was allocated a specified code in 47.7 % of cases and was mentioned in 45.9 % of narratives. The cause was missing in both in 42.8 % of cases. In approximately half of all cases, the activity and place were specified in both the coded injury variable and narrative; they were missing in both in 7.4 and 13.6 % of cases, respectively. CONCLUSIONS: The reliability of the VEMD as an injury surveillance system, varied depending on the injury variable being examined. PMID- 27405807 TI - False Lumen Status in Patients With Acute Aortic Dissection: A Systematic Review and Meta-Analysis. PMID- 27405808 TI - Association Between Hospital Performance on Patient Safety and 30-Day Mortality and Unplanned Readmission for Medicare Fee-for-Service Patients With Acute Myocardial Infarction. AB - BACKGROUND: Little is known regarding the relationship between hospital performance on adverse event rates and hospital performance on 30-day mortality and unplanned readmission rates for Medicare fee-for-service patients hospitalized for acute myocardial infarction (AMI). METHODS AND RESULTS: Using 2009-2013 medical record-abstracted patient safety data from the Agency for Healthcare Research and Quality's Medicare Patient Safety Monitoring System and hospital mortality and readmission data from the Centers for Medicare & Medicaid Services, we fitted a mixed-effects model, adjusting for hospital characteristics, to evaluate whether hospital performance on patient safety, as measured by the hospital-specific risk-standardized occurrence rate of 21 common adverse event measures for which patients were at risk, is associated with hospital-specific 30-day all-cause risk-standardized mortality and unplanned readmission rates for Medicare patients with AMI. The unit of analysis was at the hospital level. The final sample included 793 acute care hospitals that treated 30 or more Medicare patients hospitalized for AMI and had 40 or more adverse events for which patients were at risk. The occurrence rate of adverse events for which patients were at risk was 3.8%. A 1% point change in the risk-standardized occurrence rate of adverse events was associated with average changes in the same direction of 4.86% points (95% CI, 0.79-8.94) and 3.44% points (95% CI, 0.19 6.68) for the risk-standardized mortality and unplanned readmission rates, respectively. CONCLUSIONS: For Medicare fee-for-service patients discharged with AMI, hospitals with poorer patient safety performance were also more likely to have poorer performance on 30-day all-cause mortality and on unplanned readmissions. PMID- 27405809 TI - Defining a Mobile Health Roadmap for Cardiovascular Health and Disease. PMID- 27405810 TI - Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta-analysis of available randomized controlled trials. METHODS AND RESULTS: We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo-controlled randomized controlled trials investigating the effect of quercetin on BP. Meta analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect size was expressed as weighted mean difference (WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta analysis showed significant reductions both in systolic BP (WMD: -3.04 mm Hg, 95% CI: -5.75, -0.33, P=0.028) and diastolic BP (WMD: -2.63 mm Hg, 95% CI: -3.26, 2.01, P<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP-reducing effect in randomized controlled trials with doses >=500 mg/day (WMD: -4.45 mm Hg, 95% CI: -7.70, -1.21, P=0.007 and -2.98 mm Hg, 95% CI: 3.64, -2.31, P<0.001, respectively), and lack of a significant effect for doses <500 mg/day (WMD: -1.59 mm Hg, 95% CI: -4.44, 1.25, P=0.273 and -0.24 mm Hg, 95% CI: -2.00, 1.52, P=0.788, respectively), but indirect comparison tests failed to significant differences between doses. CONCLUSIONS: The results of the meta analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add-on to antihypertensive therapy. PMID- 27405811 TI - Prevalence of Eligibility Criteria for the Systolic Blood Pressure Intervention Trial in US Adults Among Excluded Groups: Age <50 Years, Diabetes Mellitus, or a History of Stroke. AB - BACKGROUND: Adults <50 years old, with diabetes mellitus, or a history of stroke were not enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). Estimating the size and characteristics of these excluded groups who meet the other SPRINT eligibility criteria may provide information on the potential impact of providers extending the SPRINT findings to these populations. METHODS AND RESULTS: We analyzed the National Health and Nutrition Examination Survey 2003 2012 (n=25 076) to estimate the percentage and characteristics of US adults >=20 years in 3 populations (age <50 years, diabetes mellitus, or history of stroke) excluded from SPRINT who otherwise meet the trial eligibility criteria: age >=50 years, systolic blood pressure (SBP) 130-180 mm Hg, high cardiovascular disease risk, and not having trial exclusion criteria. Overall, 1.0% (95% CI 0.8-1.3) of US adults age <50 years, 25.4% (95% CI 23.4-27.6) with diabetes mellitus, and 19.0% (95% CI 16.0-22.4) with history of stroke met the other SPRINT eligibility criteria. Among US adults with SBP >=130 mm Hg, other SPRINT eligibility criteria were met by 7.5% (95% CI 6.1-9.2) of those age <50 years, 32.9% (95% CI 30.5 35.4) with diabetes mellitus, and 23.0% (95% CI 19.4-27.0) with history of stroke. Among US adults meeting the other SPRINT eligibility criteria, antihypertensive medication was being taken by 31.0% (95% CI 23.9-41.3) of those <50 years, 63.0% (95% CI 58.2-67.6) with diabetes mellitus, and 68.9% (95% CI 59.4-77.1) with a history of stroke. CONCLUSIONS: A substantial percentage of US adults with diabetes mellitus or history of stroke and a small percentage <50 years old meet the other SPRINT eligibility criteria. PMID- 27405813 TI - Structural characterization and anti-aging activity of a novel extracellular polysaccharide from fungus Phellinus sp. in a mammalian system. AB - Little is known about the chemical structure of purified extracellular polysaccharides from Phellinus sp., a fungal species with known medicinal properties. A combination of IR spectroscopy, methylation analysis and NMR were performed for the structural analysis of a purified extracellular polysaccharide derived from Phellinus sp. culture, denoted as SHP-1, along with an evaluation of the anti-aging effect in vivo of the polysaccharide supplementation. The structure of SHP-1 was established, with a backbone composed of ->2,4)-alpha-d glucopyranose-(1-> and ->2)-beta-d-mannopyranose-(1-> and two terminal glucopyranose branches. Biochemical analysis from mammalian animal experiments demonstrated that SHP-1 possesses the ability to enhance antioxidant enzyme activities, such as catalase (CAT) and superoxide dismutase (SOD) activities, Trolox equivalent antioxidant capacity (TEAC) in serum of d-galactose-aged mice, while reducing lipofuscin levels, another indicator of cell aging, indicating a potential association with anti-aging activities in a dose dependent manner. This compound had a favourable influence on immune organ indices, and a marked amelioration ability of histopathological hepatic lesions such as necrosis, karyolysis and reduced inflammation and apoptosis in mouse hepatocytes. These results suggest that SHP-1 has strong antioxidant activities and a significant protective effect against oxidative stress or hepatotoxicity induced by d galactose in mice and it could be developed as a food ingredient or a pharmaceutical to prevent many age-associated diseases such as major depressive disorder and hepatotoxicity. To our knowledge, this is the first report on the antioxidant effects of a novel purified exopolysaccharide derived from Phellinus sp. PMID- 27405812 TI - Glycogen Synthase Kinase 3beta Inhibition Improves Myocardial Angiogenesis and Perfusion in a Swine Model of Metabolic Syndrome. AB - BACKGROUND: Inhibition of glycogen synthase kinase 3beta (GSK-3beta) has been reported to be cardioprotective during stressful conditions. METHODS AND RESULTS: Pigs were fed a high-fat diet for 4 weeks to develop metabolic syndrome, then underwent placement of an ameroid constrictor to their left circumflex artery to induce chronic myocardial ischemia. Two weeks later, animals received either: no drug (high cholesterol control group [HCC]) or a GSK-3beta inhibitor (GSK-3beta inhibited group [GSK-3betaI]), which were continued for 5 weeks, followed by myocardial tissue harvest. Coronary blood flow and vessel density were significantly increased in the GSK-3betaI group compared to the HCC group. Expression levels of the following proteins were greater in the GSK-3betaI group compared to the HCC group: vascular endothelial growth factor receptor 1 , vascular endothelial cadherin, gamma-catenin, beta-catenin, protein kinase B, phosphorylated forkhead box O1, and superoxide dismutase 2. CONCLUSIONS: In the setting of metabolic syndrome, inhibition of GSK-3beta increases blood flow and vessel density in chronically ischemic myocardium. We identified several angiogenic, cell survival, and differentiation pathways that include beta-catenin signaling and AKT/FOXO1, through which GSK-3beta appears to improve vessel density and blood flow. These results may provide a potential mechanism for medical therapy of patients suffering from coronary artery disease and metabolic syndrome. PMID- 27405814 TI - Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma. AB - BACKGROUND: Stereotactic body radiation therapy (SBRT) has been an emerging non invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology. METHODS: Between 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models. RESULTS: The median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 %(54-71.5 %) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 %(33.0-52.2 %) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3 16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2 91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 %(38.9-59.2 %), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (<=4 cm vs >4-9 cm />=10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable. CONCLUSIONS: Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment. PMID- 27405815 TI - Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice. AB - Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy. PMID- 27405816 TI - Implementing Community Engagement for Combination Prevention: Lessons Learnt From the First Year of the HPTN 071 (PopART) Community-Randomized Study. AB - Key to the success of a HIV combination prevention strategy, including galvanizing the current push to roll out universal test and treat (UTT), is the involvement and buy-in of the populations that the strategy aims to reach. Drawing on the experiences of engaging with 21 communities in Zambia and South Africa in the design and implementation of a community-randomized study of combination HIV prevention including UTT, this paper reflects on the commitment to, approaches for and benefits of involving communities. Key lessons learnt include that all communities require continuous community engagement (CE) and engagement needs to be adapted to diverse local contexts. Intrinsic goals of CE, such as building trusting relationships between study stakeholders, are necessary precursors to instrumental goals which strengthen the research quality. Engaging the community for combination prevention requires that CE successfully bridges science and real life, paying attention to influences in the wider social landscape. PMID- 27405817 TI - PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates. AB - PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure. PMID- 27405818 TI - Steady-state volume of distribution of two-compartment models with simultaneous linear and saturated elimination. AB - The model-independent estimation of physiological steady-state volume of distribution ([Formula: see text]), often referred to non-compartmental analysis (NCA), is historically based on the linear compartment model structure with central elimination. However the NCA-based steady-state volume of distribution ([Formula: see text]) cannot be generalized to more complex models. In the current paper, two-compartment models with simultaneous first-order and Michaelis Menten elimination are considered. In particular, two indistinguishable models [Formula: see text] and [Formula: see text], both having central Michaelis-Menten elimination, while first-order elimination exclusively either from central or peripheral compartment, are studied. The model-based expressions of the steady state volumes of distribution [Formula: see text] and their relationships to NCA based [Formula: see text] are derived. The impact of non-linearity and peripheral elimination is explicitly delineated in the formulas. Being concerned with model identifiability and indistinguishability issues, an interval estimate of [Formula: see text] is suggested. PMID- 27405820 TI - Five facts about the gender pay gap in UK medicine. PMID- 27405819 TI - Reticular Appearance on Gadolinium-enhanced T1- and Diffusion-weighted MRI, and Low Apparent Diffusion Coefficient Values in Microcystic Meningioma Cysts. AB - PURPOSE: Microcystic meningioma, a rare meningioma subtype, can present diagnostic difficulty. We aimed to investigate the historadiological properties of microcystic meningioma using conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) analysis. METHODS: We retrospectively analyzed conventional MRI and DWI results of six microcystic meningioma cases by examining their appearance and determining their apparent diffusion coefficient (ADC) values. The ADC values of the intratumoral components were normalized with ADC values of the cerebrospinal fluid in the lateral ventricle (ADC ratios). As cystic formations are frequently associated with microcystic meningiomas, their MRI characteristics were compared with the imaging data from 11 cystic meningiomas of non-microcystic subtypes. RESULTS: We found that cysts in microcystic meningioma tended to have a reticular appearance on DWI, as they did on gadolinium-enhanced T1-weighted imaging. Additionally, these reticular cysts had significantly lower ADC ratios than microcystic non-reticular and non microcystic cysts. These DWI characteristics likely reflect the histological properties of microcystic meningioma. CONCLUSION: A reticular appearance on gadolinium-enhanced T1-weighted MRI and DWI, and cyst formation with relatively low ADC values can be diagnostic markers of microcystic meningiomas. PMID- 27405821 TI - Interpregnancy interval and preterm birth: correlation versus causation debate continued. PMID- 27405822 TI - Predicting nonrecovery among whiplash patients in the emergency room and in an insurance company setting. AB - PURPOSE: To construct and validate a prediction instrument for early identification of patients with a high risk of delayed recovery after whiplash injuries (PPS-WAD) in an insurance company setting. METHODS: Prospective cohort study. On the basis of a historic cohort (n = 130) of patients with a whiplash injury identified in an emergency room (ER, model-building set), we used logistic regression to construct an instrument consisting of two demographic variables (i.e. questions of educational level and work status) and the patient-rated physical and mental status during the acute phase to predict self-reported nonrecovery after 6 months. We evaluated the instrument's ability to predict nonrecovery in a new cohort (n = 204) of patients originating from an insurance company setting (IC, validation set). RESULTS: The prediction instrument had low reproducibility when the setting was changed from the ER cohort to the IC cohort. The overall percentage of correct predictions of nonrecovery in the ER cohort was 78 % compared with 62 % in the IC cohort. The sensitivity and specificity in relation to nonrecovery were both 78 % in the ER cohort. The sensitivity and specificity in the insurance company setting was lower, 67 and 50 %. CONCLUSION: Clinical decision rules need validation before they are used in a new setting. An instrument consisting of four questions with an excellent possibility of identifying patients with a high risk of nonrecovery after a whiplash injury in the emergency room was not as useful in an insurance company setting. The importance and type of the risk factors for not recovering probably differ between the settings, as well as the individuals. PMID- 27405823 TI - A pedicle screw system and a lamina hook system provide similar primary and long term stability: a biomechanical in vitro study with quasi-static and dynamic loading conditions. AB - PURPOSE: For the stabilization of the thoracolumbar spine area, various stabilization techniques have been developed in recent decades. The aim of these techniques is to immobilize the treated segment to repositioning or correct the spine and guaranty long-term stability to achieve a reliable fusion. The aim of this study was to simulate in an in vitro experiment the postoperative long-term situation in elderly osteoporotic patients to compare two different stabilization principles; a pedicle screw system and a lamina hook system. METHODS: Two comparable groups with respect to age and bone mineral density with each n = 6 fresh-frozen human, bi-segmental thoracolumbar spine specimens (T11-L1) were used. Antero-posterior and lateral radiographs were taken before the test, to assess the spinal status. Then the intact specimens were biomechanically characterized with pure moments in the three anatomical planes in different states in terms of range of motion and neutral zone. After implantation of either, a pedicle screw system or a lamina hook system, the primary stability was determined under the same conditions. Subsequently the specimens were cyclically loaded under complex loading, using a custom-made set-up in a dynamic materials testing machine with increasing moments from 3 to 66 Nm until 100,000 cycles or until one of the three defined "failure" criteria was reached. (1) A failure of a bony structure. (2) Exceeding of the threefold ROM of the primary stability after implantation in flexion plus extension. (3) Reaching of the ROM based on the intact state before implantation both in flexion plus extension. RESULTS: The results showed that the ROM was strongly reduced after instrumentation similar for both implant systems in all motion planes. The highest stabilization was found in flexion/extension. During cyclic loading with increasing moments, the ROM increased continuously for both systems. The number of load cycles until one of the failure criteria was reached varied only slightly between the two groups. In the pedicle screw group 30,000 (median) loading cycles (range 5000-80,000) with a corresponding moment of 24 Nm (range 9-54) could be reached. In the lamina hook group 32,500 load cycles (range 20,000-45,000) could be achieved with a corresponding moment of 25.5 Nm (range 18-33). There was a slight trend that the pedicle screw system is influenced more by bone mineral density. CONCLUSION: Both implant systems provide similar primary stability and similar long-term stability. In the pedicle screw group, there was a stronger correlation between bone mineral density and the reached number of load cycles. PMID- 27405824 TI - Multimodal Imaging of Nanocomposite Microspheres for Transcatheter Intra-Arterial Drug Delivery to Liver Tumors. AB - A modern multi-functional drug carrier is critically needed to improve the efficacy of image-guided catheter-directed approaches for the treatment of hepatic malignancies. For this purpose, a nanocomposite microsphere platform was developed for selective intra-arterial transcatheter drug delivery to liver tumors. In our study, continuous microfluidic methods were used to fabricate drug loaded multimodal MRI/CT visible microspheres that included both gold nanorods and magnetic clusters. The resulting hydrophilic, deformable, and non-aggregated microspheres were mono-disperse and roughly 25 um in size. Sustained drug release and strong MRI T2 and CT contrast effects were achieved with the embedded magnetic nano-clusters and radiopaque gold nanorods. The microspheres were successfully infused through catheters selectively placed within the hepatic artery in rodent models and subsequent distribution in the targeted liver tissues and hepatic tumors confirmed with MRI and CT imaging. These multimodal nanocomposite drug carriers should be ideal for selective intra-arterial catheter directed administration to liver tumors while permitting MRI/CT visualization for patient-specific confirmation of tumor-targeted delivery. PMID- 27405825 TI - Reproducibility and validity of dietary patterns identified using factor analysis among Chinese populations. AB - In the present study, we evaluated the reproducibility and validity of dietary patterns among Chinese adult populations. A random subsample of 203 participants (aged 31-80 years) from a community-based nutrition and health survey was enrolled. An eighty-seven-item FFQ was administered twice (FFQ1 and FFQ2) 1 year apart; four 3 consecutive day, 24-h dietary recalls (24-HDR, as a reference method) were performed between the administrations of the two FFQ every 3 months. Dietary patterns from three separate dietary sources were derived using factor analysis based on twenty-eight predefined food groups. Comparisons between dietary pattern scores were made by using Pearson's or intraclass correlation coefficients (ICC), cross-classification analysis, weighted kappa statistic and Bland-Altman plots; the four major dietary patterns identified from FFQ1, FFQ2 and 24-HDR were similar. Regarding reproducibility, ICC for z-scores between FFQ1 and FFQ2 were all >0.6 for dietary patterns. The 'animal and plant protein' pattern had the highest ICC of 0.870. For validity, the adjusted Pearson's correlation coefficients for dietary pattern z-scores between two FFQ and the mean of four 3 consecutive day 24-HDR ranged from 0.387 for the 'Chinese traditional' pattern to 0.838 for the 'animal and plant protein' pattern. More than 75 % of the participants were classified into the same or adjacent quartile, and <5 % were misclassified into opposite quartiles. The weighted kappa ranged from 0.259 to 0.680. Bland-Altman plots indicated that no significant deviation was found between two dietary assessment methods. Our findings indicate a good reasonable reproducibility and a reasonable validity of dietary patterns derived by factor analysis in China. PMID- 27405826 TI - Lou Gehrig's disease linked to aldehyde oxidase. PMID- 27405827 TI - 1795-1995: Milestones in ROS research. PMID- 27405828 TI - Identification of the candidate ALS2 gene at chromosome 2q33 as a human aldehyde oxidase gene. AB - Denver, Tokyo, and Salt Lake City investigators recently published different complimentary deoxyribonucleic acid (cDNA) sequences for human liver xanthine dehydrogenase/xanthine oxidase (XD/XO). The gene encoding the Denver cDNA was subsequently linked to juvenile familial amyotrophic lateral sclerosis (JFALS) at chromosome 2q33 and has been proposed as the ALS2 locus. The present investigation was undertaken to elucidate the differences between the three cDNA sequences, and we provide evidence that the Denver cDNA encodes aldehyde oxidase (AO): first, the Denver cDNA sequence diverged significantly from the Tokyo and Salt Lake City cDNA sequences which were very similar; second, the deduced protein sequence from the Denver cDNA was very similar to the amino acid sequence of purified rabbit liver AO protein; third, the deduced Denver protein sequence was 76% identical to the encoded 101 amino acid long peptides from partial cDNAs for rabbit and rat AO and 81.7% identical to 300 amino acids from an incomplete cDNA encoding bovine AO; fourth, the Denver gene was expressed in liver, kidney, lung, pancreas, prostate, testes, and ovary while the Tokyo XD gene was expressed predominantly in liver and small intestine; fifth, the Denver gene was previously mapped to chromosome 2q33 which is syntenic to the mouse AO locus on chromosome 1. Our results have revealed dramatic similarities in protein and DNA sequence in the human molybdenum hydroxylases, have uncovered unanticipated complexity in the human molybdenum hydroxylase genes, and advance the potential for AO derived oxygen radicals in JFALS and other human diseases. PMID- 27405829 TI - Total radical-trapping antioxidative capacity of plasma and whole blood chemiluminescence in patients with inflammatory and autoimmune rheumatic diseases. AB - The total radical-trapping antioxidative capacity (TRAC) of plasma was evaluated in samples from patients suffering from various inflammatory and autoimmune rheumatic diseases (n=104) and correlated with the phorbol ester-stimulated chemiluminescence (CL) of neutrophils and monocytes in unseparated blood. Plasma and blood samples from age- and sex-matched healthy volunteers (n=25) and from patients with non-rheumatic internal diseases (n=31) served as controls. A 2 to 10 fold increase in whole blood chemiluminescence was found in rheumatic patients, which paralleled 50-80% decreased levels of plasma TRAC-values. While significant correlations between CL and TRAC were determined for patients with inflammatory arthritic diseases no correlations were found with patients suffering from connective tissue diseases. Prednisolone treatment of individual patients increased plasma TRAC-values substantially and decreased elevated levels of phagocytic CL generation to that of healthy controls. The main potential application of the assays described here is for the convenient assessment of disease activity and progression in individual patients with rheumatic diseases. PMID- 27405830 TI - Biological variability of superoxide dismutase and glutathione peroxidase in blood. AB - The enzymatic antioxidant defences of mammalian cells include copper-zinc superoxide dismutase (SOD)(Cu Zn-SOD; EC 1.15.1.1) which catalyses the dismutation of superoxide anions (O2(.-)) to hydrogen peroxide(H(2), O(2))and a seleno-dependent glutathione peroxidase (GSH-px) (GSH-px; EC 1.11.1.9) which catalyses the degradation of H(2)O(2) to H(2)O and O(2). The measurement of these enzyme activities is often used as a possible biological index of oxidative stress in various clinical conditions. Complete understanding of such information requires knowledge of the random biological fluctuation of the enzyme activity which occurs in each individual. In the present investigation we examined this normal variability in 12 healthy volunteers (four women and eight men) aged 23-45 years, over 6 months. The intra-individual coefficients of variation (estimated using analysis of variance techniques) were 15% (SOD) and 13% (GSH-px). The analytical goal for imprecision was achieved for both enzymes, i.e. it was less than one half of the measured intra-individual variation. Both enzymes showed marked individuality, indicating that an individual's reference values are more useful than population-based data. The critical difference required for significant changes in serial results is 45% for SOD and 40% for GSH-px. PMID- 27405832 TI - Protective effects of coenzyme Q10 and alpha-tocopherol against free radical mediated liver cell injury. AB - In an attempt to provide further confirmation of the antioxidant role of reduced form of coenzyme Q homologue (CoQnH2) and alpha-tocopherol (alpha-Toc), we incubated isolated rat hepatocytes with a water-soluble radical initiator, 2,2' azobis(2-amidinopropane)dihydrochloride (AAPH) in the presence or absence of exogenously added coenzyme Q10 (CoQ10) or alpha-Toc for 3 h at 37 degrees C under an atmosphere of 95% oxygen and 5% carbon dioxide. In the control experiment without adding AAPH it was confirmed that added CoQ10 and alpha-Toc were incorporated into the cells and some CoQ10 were converted to CoQ10H2. Incubation of hepatocytes with 50 mM AAPH resulted in the formation of thiobarbituric acid reactive substances and the decrease in cell viability and both were inhibited by exogenously added CoQ10 or alpha-Toc in a dose-dependent manner. The decrease in endogenous CoQ9H2 and alpha-Toc levels was observed by the addition of AAPH. Addition of CoQ10 inhibited the oxidation of CoQ9H2 to CoQ9 dose-dependently while the addition of alpha-Toc did not. These data suggest that both CoQnH2 and alpha-Toc act as antioxidants and can inhibit free radical-mediated cell injury. PMID- 27405831 TI - N-acetylcysteine pretreatment attenuates paraquat-induced lung leak in rats. AB - We investigated the effects of N-acetylcysteine (NAC) pretreatment on paraquat induced lung inflammation and leak. We found that administering a single intravenous dose (60 mg/kg) of paraquat rapidly (2 h) increased lung leak, lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels, and lung myeloperoxidase (MPO) activity in rats. Rats pretreated with NAC (150 mg/kg, intraperitoneally) had increased lung tissue glutathione (GSH + GSSG) levels compared to saline-pretreated rats. In addition, rats pretreated with NAC and then given paraquat 2.5 h later had decreased lung leak compared to saline pretreated rats given paraquat. In contrast, NAC pretreated rats given paraquat had the same lung lavage CINC levels and lung tissue MPO activity as saline pretreated rats given paraquat. Our results indicate that paraquat causes an oxidative injury which may be decreased by the GSH-increasing or other properties of NAC. PMID- 27405833 TI - Aldehyde oxidase generates deoxyribonucleic acid single strand nicks in vitro. AB - We purified aldehyde oxidase (AO) from rabbit livers and found that AO produced deoxyribonucleic acid (DNA) single strand nicks in vitro. Acetaldehyde, benzaldehyde, and certain purine bases were effective substrates for AO catalyzed DNA strand nicking. DNA strand nicking did not occur with the reducing substrates nicotinamide-adenine dinucleotide or dithionite that produce superoxide anion (O2'(-)). Inclusion of electron transport inhibitors, potassium cyanide, ferricyanide or menadione, prevented AO catalyzed nicking. AO induced DNA strand nicking was dependent upon hydrogen peroxide (H2O2) formation and most likely generation of hydroxyl radical (HO'). The present observations may be pertinent to the recently proposed involvement of AO in inherited juvenile familial amyotrophic lateral sclerosis (JFALS) and other oxygen radical mediated diseases. PMID- 27405834 TI - Inhibitory effect of ebselen on the oxidation of low density lipoprotein. AB - The inhibitory effect of a synthesized glutathione peroxidase (GSHPX) mimic- ebselen, and its cofactor glutathione (GSH), on the oxidation of low density lipoprotein (LDL) induced by Cu(2+) was studied by determination of hydroperoxides and thiobarbituric acid reactive substances (TBARS). Ebselen alone had a strong inhibitory effect on the oxidation of LDL. The lag time of LDL oxidation was prolonged with an increase in the concentration of ebselen. The inhibitory effect of 5 MUM ebselen was equivalent to that of 50 MUM alpha tocopherol. When GSH was present, ebselen exhibited stronger inhibitory effect than when present alone. With 50 MUM GSH, ebselen at a concentration as low as 5 MUM could inhibit oxidation of LDL induced by 5 MUM Cu(2+) completely for at least 24 h. Ebselen at high concentrations (100 MUM) decomposed hydroperoxides in pre-oxidized LDL and effectively prevented its further oxidation, but not in the present of EDTA. Low concentration of ebselen (5 MUM) plus GSH (50 MUM) decomposed hydroperoxides in pre-oxidized LDL whether EDTA was added or not. PMID- 27405835 TI - Evaluation of the antioxidant properties of the angiotensin-converting enzyme inhibitor, captopril and the nucleotide enhancing agent, acadesine. AB - The angiotensin-converting enzyme inhibitor, captopril and the nucleotide enhancing agent, acadesine, protect myocardial tissue from ischaemia/reperfusion induced injury. Although both drugs have well established, independent mechanisms of cardiac protection, they may also have antioxidant activity which could contribute to their beneficial action. In this study we have examined the antioxidant activity of captopril and acadesine by examining their ability to scavenge ABTS radicals, formed from the interaction of ferryl metmyoglobin with phenothiazine in the presence of hydrogen peroxide. For comparison, we compared these results to those obtained for a range of other drugs commonly used for the treatment of cardiovascular disorders. These included verapamil (arrhythmia), isosorbide dinitrate (angina), atenolol (hypertension) and enalapril (congestive heart failure). The antioxidant properties of these drugs were then compared to the well characterised antioxidants, Trolox (a water soluble vitamin E analogue), ascorbate and glutathione. Captopril and acadesine were both shown to be efficient scavengers of ABTS radicals, importantly at drug concentrations expected to be found in vivo. These data confirm that the antioxidant potential of captopril and acadesine may be an important component of their mechanism of action, with both drugs probably protecting the myocardium against oxygen derived free radicals during ischaemia/reperfusion. PMID- 27405836 TI - Interaction of the pyridoindole stobadine with alkoxyl and stable free radicals. AB - Stobadine, a pyridoindole derivative which has been synthesized in search of new antiarrhytmic drugs, was able to interact with alpha-diphenyl-beta-picrylhydrazyl (DPPH(.)) a stable free radical. Its scavenging potential was in the same order of magnitude as that of well known strong antioxidants. The scavenging effect of antioxidants tested increased in the order: stobadine, ascorbic acid, trolox, cysteine. Stobadine exerted a scavenging effect also towards alkoxyl radicals in a nonpolar solvent in the canthaxantin bleaching test. In this test stobadine was more effective than trolox. PMID- 27405837 TI - In vitro antioxidant properties of the iron chelator pyridoxal isonicotinoyl hydrazone and some of its analogs. AB - Since there are several problems with desferrioxamine (DFO) therapy, pyridoxal isonicotinoyl hydrazone (PIH) has been studied for more than 10 years as a promising new candidate for iron chelation therapy in iron-overload diseases. Iron chelation could also be helpful for experimental treatment of several other pathologies including rheumatoid arthritis and heart ischemia/reperfusion, due to the generation of oxyradicals and lipid peroxidation mediated by delocalized iron. We demonstrate here that sub-millimolar levels of PIH can inhibit the Fe(III)-EDTA/ascorbate-mediated formation of hydroxyl-like radicals as tested by the release of ethylene from 2-keto-4-methylthiobutyric acid (KMB assay) and the formation of malonaldehyde from 2-deoxyribose damage. PIH could also decrease the rates of Fe(III)-EDTA-mediated oxidation of ascorbate and block the peroxidation of liposomes of rat brain phospholipids induced by ferrous iron-EDTA. In all cases the in vitro antioxidant effectiveness of PIH was comparable to its analogs including salicylaldehyde isonicotinoyl hydrazone-and to DFO. We conclude that PIH and its analogs are effective new candidates against iron-mediated oxidative stress for use in experimental medicine. PMID- 27405838 TI - Effects of hydrostatic pressure on malondialdehyde brain contents in yellow freshwater eels. PMID- 27405839 TI - Oxygen activation and inactivation of quinolinate-producing and iron-requiring 3 hydroxyanthranilic acid oxidase: a role in hyperbaric oxygen-induced convulsions? PMID- 27405840 TI - Correspondence. PMID- 27405841 TI - Aqueous biphasic systems composed of ionic liquids and polypropylene glycol: insights into their liquid-liquid demixing mechanisms. AB - Novel ternary phase diagrams of aqueous biphasic systems (ABSs) composed of polypropylene glycol with an average molecular weight of 400 g mol(-1) (PPG-400) and a vast number of ionic liquids (ILs) were determined. The large array of selected ILs allowed us to evaluate their tuneable structural features, namely the effect of the anion nature, cation core and cation alkyl side chain length on the phase behaviour. Additional evidence on the molecular-level mechanisms which rule the phase splitting was obtained by (1)H NMR (Nuclear Magnetic Resonance) spectroscopy and by COSMO-RS (Conductor-like Screening Model for Real Solvents). Some systems, for which the IL-PPG-400 pairs are completely miscible, revealed to be of type "0". All data collected suggest that the formation of PPG-IL-based ABSs is controlled by the interactions established between the IL and PPG, contrarily to previous reports where a "salting-out" phenomenon exerted by the IL over the polymer in aqueous media was proposed as the dominant effect in ABS formation. The influence of temperature on the liquid-liquid demixing was also evaluated. In general, an increase in temperature favours the formation of an ABS in agreement with the lower critical solution temperature (LCST) phase behaviour usually observed in polymer-IL binary mixtures. Partition results of a dye (chloroanilic acid, in its neutral form) further confirm the possibility of tailoring the phases' polarities of IL-PPG-based ABSs. PMID- 27405843 TI - Radicalization and Radical Catalysis of Biomass Sugars: Insights from First principles Studies. AB - Ab initio and density functional calculations are conducted to investigate the radicalization processes and radical catalysis of biomass sugars. Structural alterations due to radicalization generally focus on the radicalized sites, and radicalization affects H-bonds in D-fructofuranose more than in D-glucopyranose, potentially with outcome of new H-bonds. Performances of different functionals and basis sets are evaluated for all radicalization processes, and enthalpy changes and Gibbs free energies for these processes are presented with high accuracy, which can be referenced for subsequent experimental and theoretical studies. It shows that radicalization can be utilized for direct transformation of biomass sugars, and for each sugar, C rather than O sites are always preferred for radicalization, thus suggesting the possibility to activate C-H bonds of biomass sugars. Radical catalysis is further combined with Bronsted acids, and it clearly states that functionalization fundamentally regulates the catalytic effects of biomass sugars. In presence of explicit water molecules, functionalization significantly affects the activation barriers and reaction energies of protonation rather than dehydration steps. Tertiary butyl and phenyl groups with large steric hindrances or hydroxyl and amino groups resulting in high stabilities for protonation products drive the protonation steps to occur facilely at ambient conditions. PMID- 27405844 TI - A non-radioactive assay for selenophosphate synthetase activity using recombinant pyruvate pyrophosphate dikinase from Thermus thermophilus HB8. AB - Biosynthesis of selenocysteine-containing proteins requires monoselenophosphate, a selenium-donor intermediate generated by selenophosphate synthetase (Sephs). A non-radioactive assay was developed as an alternative to the standard [8-(14)C] AMP-quantifying assay. The product, AMP, was measured using a recombinant pyruvate pyrophosphate dikinase from Thermus thermophilus HB8. The KM and kcat for Sephs2-Sec60Cys were determined to be 26 MUM and 0.352 min(-1), respectively. PMID- 27405842 TI - Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer. AB - Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant-antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease. PMID- 27405846 TI - Efficient production of nonactin by Streptomyces griseus subsp. griseus. AB - Here we report the production of the cyclic macrotetrolide nonactin from the fermentation culture of Streptomyces griseus subsp. griseus. Nonactin is a member of a family of naturally occurring cyclic ionophores known as the macrotetrolide antibiotics. Our fermentation procedure of Streptomyces griseus was performed at 30 degrees C and 200 rev.min(-1) for 5 days on a rotary shaker. Diaion HP-20 and Amberlite XAD-16 were added to the fermentation medium. Isolated yield of nonactin was up to 80 mg.L(-1) using our methodology. Nonactin is commonly known as an ammonium ionophore and also exhibits antibacterial, antiviral, and antitumor activities. It is also widely used for the preparation of ion-selective electrodes and sensors. Chemical synthesis of nonactin has been achieved by some groups; however, overall yields are very low, making efficient biosynthesis an attractive means of production. PMID- 27405845 TI - Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice. AB - BACKGROUND: Anti-pentraxin 3 (PTX3) antibodies were associated with the absence of lupus glomerulonephritis in humans. AIM: To explore the effects of anti-PTX3 antibodies in New Zealand Black/White (NZB/NZW F1) mice and their inherent mechanisms of action. MATERIALS AND METHODS: 30 NZB/NZW F1 mice were subdivided into 3 groups of 10 mice each and subcutaneously injected with PTX3, alum and PBS (group 1), alum and PBS (group 2) or PBS alone (group 3), 3 times 3 weeks apart, before development of renal disease. Mice were followed until natural death. Histological analysis and immunohistochemistry were performed on harvested kidneys. Effects of anti-PTX3 antibodies on C1q binding to immobilized PTX3-anti PTX3 immune complexes were evaluated in vitro using human SLE sera. Qualitative characterization of human IgG anti-PTX3 was performed. RESULTS: Only group 1 mice developed anti-PTX3 antibodies. Anti-dsDNA and anti-C1q antibodies appeared significantly later and at lower levels in group 1 mice vs. controls (p < 0.0001). Proteinuria-free and overall survival were significantly increased in group 1 mice vs. controls (p < 0.05 and p = 0.03, respectively). Histopathological analysis showed that glomerular and tubular PTX3 staining and renal lesions were increased in controls compared with immunized mice. Addition of human SLE sera positive for anti-PTX3 antibodies to C1q and fixed PTX3 interfered with C1q binding to PTX3-anti-PTX3 immune complexes. Qualitative characterization of human IgG anti-PTX3 showed an increased proportion of IgG4. CONCLUSIONS: Anti-PTX3 antibodies delay lupus-like nephritis and prolong survival of NZB/NZW F1 mice. In vitro observations suggest anti-PTX3 antibodies may dampen complement activation via their Fc fragment, likely hindering renal inflammation. PMID- 27405847 TI - Comprehensive method to predict and quantify scald burns from beverage spills. AB - A comprehensive study was performed to quantify the risk of burns from hot beverage spills. The study was comprised of three parts. First, experiments were carried out to measure the cooling rates of beverages in a room-temperature environment by natural convection and thermal radiation. The experiments accounted for different beverage volumes, initial temperatures, cooling period between the time of service and the spill, the material which comprised the cup, the presence or absence of a cap and the presence or absence of an insulating corrugated paper sleeve. Among this list, the parameters which most influenced the temperature variation was the presence or absence of a cover or cap, the volume of the beverage and the duration of the cooling period. The second step was a series of experiments that provided temperatures at the surface of skin or skin surrogate after a spill. The experiments incorporated a single layer of cotton clothing and the exposure duration was 30 s. The outcomes of the experiments were used as input to a numerical model which calculated the temperature distribution and burn depth within tissue. Last was the implementation of the numerical model and a catalogue of burn predictions for various beverage volumes, beverage service temperatures, and durations between beverage service and spill. It is hoped that this catalogue can be used by both beverage industries and consumers to reduce the threat of burn injuries. It can also be used by treating medical professionals who can quickly estimate burn depths following a spill incident. PMID- 27405849 TI - 14th Urological Association of Asia Congress 2016 Singapore | 20 - 24 July 2016 "UROLOGICAL ADVANCEMENT IN ASIA" in conjunction with UROFAIR 2016 Urology Residents' Course 2016 and the 30th Anniversary of the Singapore Urological Association. PMID- 27405848 TI - PTSD treatment in light of DSM-5 and the "golden hours" concept. AB - One of the main changes in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was the separation of Stress Related Disorders from the Anxiety chapter. This separation paves the way to examine the unique characteristics of posttraumatic stress disorder (PTSD) (ie, identifiable onset, memory processes, etc) and related neural mechanisms. The time that elapses between the traumatic event and the manifestation of the disorder may also be addressed as the "golden hours," or the window of opportunity in which critical processes take place and relevant interventions may be administrated. PMID- 27405851 TI - DNA-fueled molecular machine for label-free and non-enzymatic ultrasensitive detection of telomerase activity. AB - Herein, a non-enzymatic and label-free strategy based on DNA-fueled molecular machine was developed for ultrasensitive detection of telomerase activity in cancer cell extracts even at the single-cell level. PMID- 27405852 TI - Neuroprotective effects of Paeonia Lactiflora extract against cell death of dopaminergic SH-SY5Y cells is mediated by epigenetic modulation. AB - BACKGROUND: The Paeonia lactiflora extract (PLE) has been reported to have neuroprotective effect against neurodegeneration that are induced by cellular stress such as oxidative stress. Its underlying mechanisms, however, remain unclear. In latest decades, emerging evidence has suggested that epigenetic mechanisms play a key role in gene regulation in response to the cellular stress. We investigated whether epigenetic modulation was involved in neuronal cell death by the neurotoxicant, 1-Methyl-4-phenylpyridinium (MPP(+)), and the neuroprotective effect of PLE. METHODS: Differentiated SH-SY5Y, which is a well established dopaminergic cell line model, was treated with 0 ~ 200 MUg/ml PLE for 4 h prior to MPP(+) treatment. The effect of PLE on cell viability was determined by MTT assays. Gene expression levels of oxidative stress responsive genes, such as Heme oxygenase 1 (HMOX1), and histone modifiers, such as histone acetyltransferases (HATs) and deacetylases (HDACs) were measured by quantitative RT PCR. In order to investigate the changes in epigenetic modifications, the acetylated lysine 9 (H3K9ac) and lysine 27 (H3K27ac) of Histone H3 were measured by western blot using histones extracted from the cells. RESULTS: MPP(+)-induced cell death in SH-SY5Y cells was significantly reduced by PLE pretreatment in a dose-dependent manner, indicating the potent neuroprotective effects of PLE. It was accompanied by induced expression of HMOX1. MPP(+) treatment increased the expression of HATs and consistently increased H3K9ac and H3K27ac of Histone H3. PLE pretreatment impeded the changes in H3K9ac and H3K27ac, coincided with increased expression of HDAC5 without changes in HAT expression. CONCLUSIONS: The results suggested that MPP(+)-induced cell death in the dopaminergic SH-SY5Y cells was related with transcriptional induction of HATs and increased histone H3 acetylation and that PLE might prevent the cells from MPP(+)-induced cell death via tempering histone H3 acetylation. PMID- 27405853 TI - Presence of an Alcohol Use Disorder is Associated with Greater Pneumonia Severity in Hospitalized HIV-Infected Patients. AB - PURPOSE: Pneumonia is common and more severe in human immunodeficiency virus (HIV)-infected patients. Alcohol consumption in pneumonia patients without HIV is associated with excess mortality and morbidity. However, studies are lacking on the impact of alcohol on pneumonia and HIV. Our goal was to determine if alcohol use was an independent risk factor for pneumonia severity in HIV-infected patients. METHODS: Secondary analysis of prospective cohort study data evaluating early bronchoscopy for pneumonia diagnosis in HIV patients between 2007 and 2011 was conducted. We defined AUDs using an alcohol use disorder identification test (AUDIT) score as follows: >=8 indicates hazardous drinking and >=14 indicates dependence. We quantified pneumonia severity using the pneumonia severity index (PSI). Multivariable linear regression was used to investigate the independent association between alcohol and pneumonia severity. RESULTS: A total of 196 HIV+ individuals comprised our cohort. Most cohort subjects were middle-aged African American men. Most subjects (70 %) reported not taking antiretroviral therapy. The overall prevalence of hazardous drinking was 24 % in our cohort (48/196) with 10 % (19/196) meeting the criteria for alcohol dependence. Alcohol consumption was significantly associated with pneumonia severity (r = 0.25, p < 0.001). Hazardous drinking (beta-coefficient 10.12, 95 % CI 2.95-17.29, p = 0.006) and alcohol dependence (beta-coefficient 12.89, 95 % CI 2.59-23.18, p = 0.014) were independent risk factors for pneumonia severity. Reported homelessness and men who have sex with men (MSM) status remained independent risk factors for more severe pneumonia after adjustment for the effects of alcohol. CONCLUSIONS: In a cohort of HIV patients with pneumonia, presence of an AUD was an independent risk factor for pneumonia severity. Homelessness and MSM status were associated with greater pneumonia severity in AUD patients. PMID- 27405855 TI - Feed and fuel: the dual-purpose advantage of an industrial sweetpotato. AB - BACKGROUND: Sustainable agricultural systems must support nutritional requirements, meet the energy demands of a growing population, preserve environmental resources and mitigate climate change. The sweetpotato (Ipomoea batatas L.) is a high-yielding crop that requires minimal fertilization and irrigation, and the CX-1 industrial cultivar offers superior potential for feed and fuel. RESULTS: CX-1 had the highest agronomic fresh vine yield (51.5 t ha-1 ), averaged over two cropping seasons, compared with Hernandez (33.7) and Beauregard (21.8) varieties. CX-1 vines were more nutritional than the table varieties, specifically in regard to relative feed value (205), water-soluble carbohydrates (171 g kg-1 dry matter (DM)), total digestible nutrients (643 g kg 1 DM), metabolizable energy (10.2 MJ kg-1 DM) and organic matter digestibility. Their lower fiber and lignin concentrations contributed to their freshness and digestibility throughout maturity. Significantly higher iron concentrations make the CX-1 vines a valuable, low-fat iron supplement for animal feed. The CX-1 roots also showed the highest bioethanol potential (82.3 g ethanol kg-1 fresh root) compared to Hernandez (64.5) and Beauregard (48.1). CONCLUSION: The CX-1 industrial sweetpotato is an ideal dual-purpose crop for tropical/subtropical climates that can be utilized as a non-grain-based feedstock for bioethanol production while contributing a valuable, high-yielding nutritional supplement for animal feed. (c) 2016 Society of Chemical Industry. PMID- 27405854 TI - The Roles of the Charlson Comorbidity Index and Time to First Antibiotic Dose as Predictors of Outcome in Pneumococcal Community-Acquired Pneumonia. AB - PURPOSE: In this retrospective study, we aimed to investigate the role of comorbidities using the Charlson comorbidity index (CCI) and time to first antibiotic dose (TFAD) in patients with pneumococcal community-acquired pneumonia (PCAP). METHODS: All consecutive ER admissions with PCAP who were hospitalized in the University Hospital, Zurich between 2006 and 2012 were included. The primary outcome was to determine possible determinants of all-cause in-hospital mortality (ACIHM). The second endpoint was to detect risk factors for adverse events (AEs) and determinants of length of stay (LOS). RESULTS: 108 subjects (mean age 57.6 years) were included. The median (IQR) CCI was 4 (1, 8). The median (IQR) TFAD was 210 (150, 280) min. ACIHM was 6.5 % (7/108), and median (IQR) LOS was 9 (6, 14) days. PCAP-related AEs were observed in 57 cases (52.8 %). In the multivariable analysis, neither CCI nor TFAD was associated with the outcome measures. Pneumonia severity index (PSI) was the only statistically significant predictor of ACIHM (HR 1.31/10 point increase, 95 % CI 1.12-1.53, p = 0.001) and AE rate (OR 1.31, 95 % CI 1.15-1.50, p < 0.001). CONCLUSIONS: In this study including comparatively young patients with rather mild disease severity, we found no strong evidence supporting that CCI or TFAD influenced short-term outcome measures of PCAP. Yet, pneumonia severity appears to be the most important factor for the outcome. PMID- 27405856 TI - Letter to the Editor regarding "High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study". PMID- 27405857 TI - Chiral supramolecular polymerization leading to eye differentiable circular polarization in luminescence. AB - This work demonstrates a simple methodology to tune the chiroptical properties of chiral europium(iii) complexes by supramolecular polymerization. Helical aggregation of the cesium derivative has updated the highest luminescence dissymmetry factor to date leading to naked eye visualization of circular polarized luminescence using circularly polarized filters. PMID- 27405858 TI - Development of a two-step protocol for culture expansion of human annulus fibrosus cells with TGF-beta1 and FGF-2. AB - BACKGROUND: Different biologic approaches to treat disc regeneration, including growth factors (GFs) application, are currently under investigation. Human annulus fibrosus (hAF) repair or regeneration is one of the key elements for maintenance and restoration of nucleus pulposus function. However, so far there is no effective treatment for this purpose. The aim of the present study was to investigate the response of hAF cells to different combinations of GFs, and develop a protocol for efficient culture expansion. METHODS: hAF cells were harvested from degenerated disc tissues during surgical intervertebral disc removal, and hAF cells were expanded in a monolayer. The experiments were categorized based on different protocols with transforming growth factor (TGF beta1) and fibroblast growth factor (FGF-2) culture for 14 days: group 1 had no GFs (control group); group 2 received TGF-beta1; group 3 received FGF-2; group 4 received both GFs; and group 5 (two-step) received both GFs for the first 10 days and TGF-beta1 only for the next 4 days. Cell proliferation, collagen, and noncollagen extracellular matrix (ECM) production and genes expression were compared among these groups. RESULTS: At days 3, 7 and 10 of cultivation, groups 4 and 5 had significantly more cell numbers and faster cell proliferation rates than groups 1, 2, and 3. At 14 days of cultivation, significantly more cell numbers were observed in groups 3 and 4 than in group 5. The group 4 had the most cell numbers and the fastest proliferation rate at 14 days of cultivation. After normalization for cell numbers, group 5 (two-step) produced the most collagen and noncollagen ECM at 10 and 14 days of cultivation among the five groups. In group 5, ECM gene expression was significantly upregulated. High expression of matrix metalloproteinase-1 was upregulated with FGF-2 on the different days as compared to the other groups. Annulus fibrosus cell phenotypes were only marginally retained under the different protocols based on quantitative polymerase chain reaction results. CONCLUSION: Taken together, the two-step protocol was the most efficient among these different protocols with the most abundant ECM production after normalization for cell numbers for culture expansion of hAF cells. The protocol may be useful in further cell therapy and tissue engineering approaches for disc regeneration. PMID- 27405860 TI - The Insulin Resistance Intervention after Stroke trial: A perspective on future practice and research. AB - The prevention of recurrent events after ischaemic stroke and transient ischaemic attack is well established and based on lifestyle changes, antithrombotics, statins, antihypertensives and carotid surgery. The international IRIS trial assessed whether pioglitazone, a glucose-lowering insulin-sensitizing drug, would reduce recurrent vascular events in patients with ischaemic stroke or transient ischaemic attack. After 4.8 years, pioglitazone therapy was associated with reduced vascular events and new diabetes, and an increase in weight, oedema and bone fractures. Pioglitazone may add to the strategies for preventing further events in patients with stroke or transient ischaemic attack. PMID- 27405859 TI - Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH - General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial. AB - RATIONALE: Endovascular therapy after acute ischemic stroke due to large vessel occlusion is now standard of care. There is equipoise as to what kind of anesthesia patients should receive during the procedure. Observational studies suggest that general anesthesia is associated with worse outcomes compared to conscious sedation. However, the findings may have been biased. Randomized clinical trials are needed to determine whether the choice of anesthesia may influence outcome. AIM AND HYPOTHESIS: The objective of GOLIATH (General or Local Anestesia in Intra Arterial Therapy) is to examine whether the choice of anesthetic regime during endovascular therapy for acute ischemic stroke influence patient outcome. Our hypothesis is that that conscious sedation is associated with less infarct growth and better functional outcome. METHODS: GOLIATH is an investigator-initiated, single-center, randomized study. Patients with acute ischemic stroke, scheduled for endovascular therapy, are randomized to receive either general anesthesia or conscious sedation. STUDY OUTCOMES: The primary outcome measure is infarct growth after 48-72 h (determined by serial diffusion weighted magnetic resonance imaging). Secondary outcomes include 90-day modified Rankin Scale score, time parameters, blood pressure variables, use of vasopressors, procedural and anesthetic complications, success of revascularization, radiation dose, and amount of contrast media. DISCUSSION: Choice of anesthesia may influence outcome in acute ischemic stroke patients undergoing endovascular therapy. The results from this study may guide future decisions regarding the optimal anesthetic regime for endovascular therapy. In addition, this study may provide preliminary data for a multicenter randomized trial. PMID- 27405861 TI - Cultural issues of the National Institutes of Health Stroke Scale dysphasia and dysarthria components in Singapore - A survey of healthcare workers. PMID- 27405862 TI - [Surgery of varicose vein insufficiency]. AB - The basis of surgery of great saphenous vein insufficiency is the concept of "privat circulation" coined by Trendelenburg in 1891. It was only logical that the dissection of the insuffcient vein or it's partial or complete resection could bring about healing. Over the years varicose vein stripping was modified to finally result in the highly effectiv concept of crossectomy and stripping. For decades this was the Goldstandard in surgery of varicose vein insufficiency. All the other minimally invasive therapeutic techniques which have been developed in the last decades had to compete with crossectomy and stripping. Thanks to progress in technical development the classic stripping procedure has been replaced by highly effectiv, minimally invasiv procedures, at least in the western industrialisied countries. For a minority of patients with specific anatomical pathologies as well as countries with limited health resources vein stripping remains a surgical standard procedure. PMID- 27405863 TI - [Venous ulcer]. AB - Venous disorders causing a permanent increase in venous pressure are by far the most frequent reason for ulcers of the lower extremity. With a prevalence of 1 % in the general population rising to 4 % in the elderly over 80 and its chronic character, 1 % of healthcare budgets of the western world are spent on treatment of venous ulcers. A thorough investigation of the underlying venous disorder is the prerequisite for a differenciated therapy. This should comprise elimination of venous reflux as well as local wound management. Chronic ulcers can successfully be treated by shave therapy and split skin grafting. Compression therapy is a basic measure not only in venous ulcer treatment but also in prevention of ulcer recurrence. Differential diagnosis which have to be considered are arterial ulcers, vasculitis and neoplasms. PMID- 27405864 TI - Ivabradine: A Review of Labeled and Off-Label Uses. AB - Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data. PMID- 27405865 TI - Basophils and mast cells in immunity and inflammation. PMID- 27405866 TI - The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection. AB - The innate immune system is essential for the detection and elimination of bacterial pathogens. Upon inflammasome activation, caspase-1 cleaves pro-IL-1beta and pro-IL-18 to their mature forms IL-1beta and IL-18, respectively, and the cell undergoes inflammatory death termed pyroptosis. Here, we reviewed recent findings demonstrating that Brucella abortus ligands activate NLRP3 and AIM2 inflammasomes which lead to control of infection. This protective effect is due to the inflammatory response caused by IL-1beta and IL-18 rather than cell death. Brucella DNA is sensed by AIM2 and bacteria-induced mitochondrial reactive oxygen species is detected by NLRP3. However, deregulation of pro-inflammatory cytokine production can lead to immunopathology. Nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder termed neurobrucellosis. Herein, we discuss the mechanism of caspase-1 activation and IL-1beta secretion in glial cells infected with B. abortus. Our results demonstrate that the ASC inflammasome is indispensable for inducing the activation of caspase-1 and secretion of IL-1beta upon infection of astrocytes and microglia with Brucella. Moreover, our results demonstrate that secretion of IL-1beta by Brucella-infected glial cells depends on NLRP3 and AIM2 and leads to neurobrucellosis. Further, the inhibition of the host cell inflammasome as an immune evasion strategy has been described for bacterial pathogens. We discuss here that the bacterial type IV secretion system VirB is required for inflammasome activation in host cells during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes mainly NLRP3 and AIM2 that collectively orchestrate a robust caspase-1 activation and pro-inflammatory response. PMID- 27405867 TI - The CREB3-Herp signalling module limits the cytosolic calcium concentration increase and apoptosis induced by poliovirus. AB - Poliovirus (PV)-induced apoptosis seems to play a major role in central nervous system (CNS) tissue injury, a crucial feature of the pathogenesis of poliomyelitis. We have previously shown that calcium (Ca2+) flux from the endoplasmic reticulum (ER) to the cytosol during PV infection is involved in apoptosis induction in human neuroblastoma cells. We show here that PV infection is associated with a transient upregulation of Herp (homocysteine-induced ER protein), a protein known to promote the degradation of ER-resident Ca2+ channels. Herp gene transcription is controlled by the transcription factor CREB3 (cAMP response element-binding protein 3). We found that the CREB3/Herp pathway limited the increase in cytosolic Ca2+ concentration and apoptosis early in PV infection. This may reduce the extent of PV-induced damage to the CNS during poliomyelitis. PMID- 27405868 TI - Non-centrosomal nucleation mediated by augmin organizes microtubules in post mitotic neurons and controls axonal microtubule polarity. AB - Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. In newborn migrating neurons, the microtubule network is organized by the centrosome. During neuron maturation, however, the centrosome gradually loses this activity, and how microtubules are organized in more mature neurons remains poorly understood. Here, we demonstrate that microtubule organization in post-mitotic neurons strongly depends on non-centrosomal nucleation mediated by augmin and by the nucleator gammaTuRC. Disruption of either complex not only reduces microtubule density but also microtubule bundling. These microtubule defects impair neurite formation, interfere with axon specification and growth, and disrupt axonal trafficking. In axons augmin does not merely mediate nucleation of microtubules but ensures their uniform plus end-out orientation. Thus, the augmin-gammaTuRC module, initially identified in mitotic cells, may be commonly used to generate and maintain microtubule configurations with specific polarity. PMID- 27405869 TI - Transfusion-transmitted severe Plasmodium knowlesi malaria in a splenectomized patient with beta-thalassaemia major in Sabah, Malaysia: a case report. AB - BACKGROUND: Transfusion-transmitted malaria (TTM) is a well-recognized risk of receiving blood transfusions, and has occurred with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. The simian parasite Plasmodium knowlesi is also known to be transmissible through inoculation of infected blood, and this species is now the most common cause of malaria in Malaysia with a high rate of severity and fatal cases reported. No confirmed case of accidental transfusion-transmitted P. knowlesi has yet been reported. CASE PRESENTATION: A 23-year old splenectomized patient with beta thalassaemia major presented with fever 11 days after receiving a blood transfusion from a pre symptomatic donor who presented with knowlesi malaria 12 days following blood donation. The infection resulted in severe disease in the recipient, with a parasite count of 84,000/uL and associated metabolic acidosis and multi-organ failure. She was treated with intravenous artesunate and made a good recovery. Sequencing of a highly diverse 649-base pair fragment of the P. knowlesi bifunctional dihydrofolate reductase-thymidylate synthase gene (pkdhfr) revealed that the recipient and donor shared the same haplotype. CONCLUSIONS: This case demonstrates that acquisition of P. knowlesi from blood transfusion can occur, and that clinical consequences can be severe. Furthermore, this case raises the possibility that thalassaemic patients, particularly those who are splenectomized, may represent a high-risk group for TTM and severe malaria. With rising P. knowlesi incidence, further studies in Sabah are required to determine the risk of TTM in order to guide screening strategies for blood transfusion services. PMID- 27405870 TI - Developing and testing a measure of consultation-based reassurance for people with low back pain in primary care: a cross-sectional study. AB - BACKGROUND: Reassurance from physicians is commonly recommended in guidelines for the management of low back pain (LBP), but the process of reassurance and its impact on patients is poorly researched. We aimed to develop a valid and reliable measure of the process of reassurance during LBP consultations. METHODS: Items representing the data-gathering stage of the consultation and affective and cognitive reassurance were generated from literature on physician-patient communication and piloted with expert researchers and physicians, a Patient and Public Involvement group, and LBP patients to form a questionnaire. Patients presenting for LBP at 43 General Practice surgeries were sent the questionnaire. The questionnaire was analysed with Rasch modelling, using two samples from the same population of recent LBP consultations: the first (n = 157, follow-up n = 84) for exploratory analysis and the second (n = 162, follow-up n = 74) for confirmatory testing. Responses to the questionnaire were compared with responses to satisfaction and enablement scales to assess the external validity of the items, and participants completed the questionnaire again one-week later to assess test-retest reliability. RESULTS: The questionnaire was separated into four subscales: data-gathering, relationship-building, generic reassurance, and cognitive reassurance, each containing three items. All subscales showed good validity within the Rasch models, and good reliability based on person- and item separations and test-retest reliability. All four subscales were significantly positively correlated with satisfaction and enablement for both samples. The final version of the questionnaire is presented here. CONCLUSIONS: Overall, the measure has demonstrated a good level of validity and generally acceptable reliability. This is the first measure to focus specifically on reassurance for LBP in primary care settings, and will enable researchers to further understanding of what is reassuring within the context of low back pain consultations, and how outcomes are affected by different types of reassurance. Additionally, the measure may provide a useful training and audit tool for physicians. The new measure requires testing in prospective cohorts, and would benefit from further validation against ethnographic observation of consultations in real time. PMID- 27405871 TI - Quality of life in aphasic patients 1 year after a first stroke. AB - PURPOSE: This study had twofold objective: (1) assessing change and dynamic processes over time between severity of aphasia and functional autonomy and (2) examining the temporal relationships between functional autonomy, depressive mood and quality of life in stroke patients with aphasia. METHOD: Prospective study of patients with aphasia consecutively included after a first stroke and examined 1 year later at home (n = 101). Assessment included a visual analogical scale assessing QoL, a functional autonomy scale, a severity of aphasia scale, a communication questionnaire and a depression scale. Structural equation modeling was used to estimate competitive models, in which depressive mood or QoL was the ultimate endogenous variable (i.e., vulnerability vs. scar model). RESULTS: One year after stroke, there were a slight improvement in language impairment (stability coefficient = .61, p < .001) and a moderate improvement in functional autonomy (stability coefficient = .44, p < .001). There were prospective reciprocal effects between severity of aphasia and functional autonomy, i.e., each state exerted a temporal dynamic prediction on the other over time. Cross sectional results from path analysis showed that depressive mood negatively predicted QoL (i.e., scar model); there was no evidence of the reverse association. CONCLUSION: Results and their practical relevance in treatment were discussed. Predicting as soon as possible which factors would be related to late QoL in stroke patients with aphasia is of major importance. PMID- 27405872 TI - Parental Involvement in Cognitive Behavior Therapy for Children with Anxiety Disorders: 3-Year Follow-Up. AB - Parental factors have been linked to childhood anxiety, hence, parental involvement in cognitive behavioral therapy (CBT) for anxious children has been examined. However, findings do not consistently show added effects of parent enhanced CBT, longitudinal investigations are scarce and long-term effects unclear. In the present study, 40 out of 54 families who, 3 years previously, completed one of two types of CBT treatment: with limited or active parental involvement, were assessed using semi-structured diagnostic interviews. Diagnostic status at 3-years follow-up was compared between groups. Changes in diagnostic status across assessment points: posttreatment, 6-month and 3-year follow-up were analyzed within groups. Diagnostic change from 6-month to 3-year follow-up was compared between groups. Intent-to-treat analyses revealed no significant difference in diagnostic status between groups at 3-year follow-up. Nonetheless, children whose parents actively participated in treatment showed significantly more remission from 6-month to 3-year follow-up than children with limited parental participation. PMID- 27405873 TI - Quantification of ascorbic acid and acetylsalicylic acid in effervescent tablets by CZE-UV and identification of related degradation products by heart-cut CZE-CZE MS. AB - Capillary electrophoresis is commonly applied for the analysis of pharmaceutical products due to its high separation efficiency and selectivity. For this purpose, electrospray-ionization-(ESI)-interfering additives or electrolytes are often required, which complicates the identification of impurities and degradation products by mass spectrometry (MS). Here, a capillary zone electrophoresis (CZE) method with ultraviolet (UV) absorption detection for the simultaneous determination and quantification of ascorbic acid and acetylsalicylic acid in effervescent tablets was developed. Related degradation products were identified via CZE-CZE-MS. Systematic optimization yielded 100 mM tricine (pH = 8.8) as appropriate background electrolyte, resulting in baseline separation of ascorbic acid, acetylsalicylic acid, and related anionic UV-active degradation products. The CZE-UV method was successfully validated regarding the guidelines of the Food and Drug Administration. The validated method was applied to trace the degradation rate of the active pharmaceutical ingredients at defined ambient conditions. A heart-cut CZE-CZE-MS approach, including a 4-port-nL-valve, was performed for the identification of the observed degradation products. This 2D setup enables a precise cutting of accurate sample volumes (20 nL) and the independent operation of two physically separated CZE dimensions, which is especially beneficial regarding MS detection. Hence, the ESI-interfering tricine electrolyte components were separated from the analytes in a second electrophoretic dimension prior to ESI-MS detection. The degradation products were identified as salicylic acid and mono- and diacetylated ascorbic acid. This setup is expected to be generally applicable for the mass spectrometric characterization of CZE separated analytes in highly ESI-interfering electrolyte systems. Graphical Abstract A CZE-UV method for the quantification of effervescent tablet ingredients and degradation products was developed and validated. In order to identify unknown degradation products separated in the CZE UV, a 2D heart-cut approach was performed applying a mechanical 4-port-valve. The unknown substances were transferred from the 1st to the 2nd dimension followed by the separation of ESI-interfering tricine from the analytes prior to mass spectrometric detection. PMID- 27405875 TI - Solid phase microextraction and gas chromatography-mass spectrometry methods for residual solvent assessment in seized cocaine and heroin. AB - A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3 methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 degrees C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014. PMID- 27405874 TI - Metabolomics profiling of the free and total oxidised lipids in urine by LC MS/MS: application in patients with rheumatoid arthritis. AB - Oxidised lipids, covering enzymatic and auto-oxidation-synthesised mediators, are important signalling metabolites in inflammation while also providing a readout for oxidative stress, both of which are prominent physiological processes in a plethora of diseases. Excretion of these metabolites via urine is enhanced through the phase-II conjugation with glucuronic acid, resulting in increased hydrophilicity of these lipid mediators. Here, we developed a bovine liver-beta glucuronidase hydrolysing sample preparation method, using liquid chromatography coupled to tandem mass spectrometry to analyse the total urinary oxidised lipid profile including the prostaglandins, isoprostanes, dihydroxy-fatty acids, hydroxy-fatty acids and the nitro-fatty acids. Our method detected more than 70 oxidised lipids biosynthesised from two non-enzymatic and three enzymatic pathways in urine samples. The total oxidised lipid profiling method was developed and validated for human urine and was demonstrated for urine samples from patients with rheumatoid arthritis. Pro-inflammatory mediators PGF2alpha and PGF3alpha and oxidative stress markers iPF2alpha- IV, 11-HETE and 14-HDoHE were positively associated with improvement of disease activity score. Furthermore, the anti-inflammatory nitro-fatty acids were negatively associated with baseline disease activity. In conclusion, the developed methodology expands the current metabolic profiling of oxidised lipids in urine, and its application will enhance our understanding of the role these bioactive metabolites play in health and disease. PMID- 27405876 TI - Interleukin 21 - its potential role in the therapy of B-cell lymphomas. AB - Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL 21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL 21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B cell associated malignancies. These effects are predominantly mediated by IL-21's ability to activate cytolytic activities by NK-cells and CD4+/CD8+ T-cells. In this review, we provide an overview of IL-21's effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas. PMID- 27405877 TI - The development of spontaneous trait inferences about the actor and spontaneous trait transferences about the informant: Evidence from children aged 8-13 years. AB - In social-cognitive research, little attention has been paid to the developmental course of spontaneous trait inferences about the actor (STIs about the actor) and spontaneous trait transferences about the informant (STTs about the informant). Using a false recognition paradigm, Study 1 investigated the developmental course of STIs and Study 2 investigated the developmental course of STTs, comparing 8-, 9-, 10-, 11-, 12- and 13-year olds. The results of Study 1 showed that 8-year olds could make STIs about the actor, and the magnitude of STIs increased from ages 8 to 10 years, stabilised at the age of 10, 11, 12 years, and decreased from ages 12 through 13 years. The results of Study 2 showed that 8-year olds could make STTs about the informant, and the magnitude of STTs did not vary with age. In all age groups, the magnitude of STIs about the actor was greater than that of STTs about the informant. PMID- 27405878 TI - Small increase in alcohol duty may cut violence related emergency department visits. PMID- 27405879 TI - Prediction of Post-interventional Outcome in Great Saphenous Vein Incompetence: The Role of Venous Plethysmography with Selective Superficial Vein Occlusion. AB - OBJECTIVE/BACKGROUND: To evaluate whether the outcome of radiofrequency ablation (RFA) treatment of great saphenous vein (GSV) incompetence may be predicted using strain-gauge plethysmography (SGP) with selective occlusion of the superficial venous system. METHODS: Seventeen patients (20 limbs) underwent endovenous RFA treatment for GSV incompetence (Clinical Etiology Anatomy Pathophysiology classification C2-C5; "C-group"). Duplex ultrasound (DUS) and SGP were performed with selective occlusion of superficial veins before and after RFA. Selective superficial occlusion was validated, in a control group (C-group) of 12 patients (14 legs), by ascending phlebography. In the RFA group, the time taken to reach 50% and 90% (T50, T90) of maximum venous volume was measured, as well as relative maximal reflux rates (%EV/min). The methodological error and coefficient of variation (CV) were assessed. RESULTS: Nineteen of 20 legs had complete post operative GSV obliteration using DUS, and refilling times were improved after RFA (T50 11 +/- 3 vs. 19 +/- 3 s; p < .001; T90 27 +/- 5 vs. 47 +/- 6 s; p < .001). With SGP, the methodological error and CV for T50 were 4 s and 16%, respectively. Equivalence between pre-operative superficial occlusion and post-operative baseline measurements was achieved in 15 of 17 legs for T50, and 12 of 17 for T90 (three of the 20 legs were excluded due to treatment failure [n = 1], and untreated perforating veins [n = 2]). Mean differences (95% confidence interval) were within the equivalence ranges (T50 1 [-1 to 3] seconds; T90 -3 [-11 to 4] seconds). In the C-group superficial vein occlusion was possible in 12 of 14 legs. The remaining patient (two legs) showed incomplete superficial vein occlusion at ankle level (lipodermatosclerosis) and complete superficial vein occlusion at calf level. CONCLUSION: SGP with standardized superficial venous occlusion seems to be a reliable method for identifying venous reflux and may be useful in predicting the results of successful RFA treatment. PMID- 27405880 TI - Highly Thermostable, Non-oxidizable Indium, Gallium, and Aluminium Perfluorophthalocyanines with n-Type Character. AB - Perfluorophthalocyanines incorporating three-valent metals, namely In(Cl), Ga(Cl), and Al(Cl), have been synthesized and characterized. Thermogravimetric analysis revealed that these compounds exhibit outstanding thermal stability and a tendency to sublime at a temperature exceeding around 350 degrees C without thermal decomposition. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to probe the frontier orbital energy levels of these compounds in THF solution. All three compounds undergo three quasi-reversible reductions with the first one leading to the formation of an anion radical, namely MPc(-.) , as confirmed by spectroelectrochemistry. The compounds studied were intrinsically resistive to oxidation, which indicates that they are very good electron acceptors (n-type materials). The HOMO-LUMO energy gaps (Eg ) of the three compounds determined by UV/Vis spectroscopy were relatively unaffected by the three-valent metals incorporated into the phthalocyanine macrocycle. Similarly, the energies of the HOMO (EHOMO ) and LUMO (ELUMO ) orbitals remained virtually unaffected by the three-valent metals in the perfluorophthalocyanine. Importantly, all the perfluorophthalocyanines studied possess LUMO levels between -4.76 and -4.85 eV, which makes their reduced forms resistant to electron trapping by O2 and H2 O. This property opens up the possibility for the fabrication of electronic devices operating under ambient conditions. All three compounds demonstrated very good photostability as solid thin films. PMID- 27405882 TI - Dynamic parameters of three-point crutch gait in female patients after total hip arthroplasty. AB - PURPOSE: Patient recovery after a surgical procedure depends, among other factors, on the amount of the body weight with which patient loads lower limb. Research studies report different results of the degree of body weight with which lower limb is loaded during three-point crutch gait. The aim of this study was to evaluate the level of the ground reaction forces (GRF) during crutch gait used by patients after total hip arthroplasty (THA) in the first week after discharge from the orthopaedic units. METHODS: Ten female patients diagnosed with primary unilateral coxarthrosis participated in a single measurement session. In order to record kinematic and dynamic variables of this gait pattern motion analysis system was used together with two force plates. The static test of body weight distribution between lower limbs was performed on a dual-top stabilometric plate. RESULTS: The average peak values of loading on the operated (O) limb during mid stance and terminal stance of three-point crutch gait were 64.6% and 64.3% of body weight (BW), respectively, whereas in the case of the nonoperated (NO) limb 103.5%BW and 108.8%BW, respectively. The maximum loads on the crutches were significantly higher (by 9%BW) on the NO side as compared to the O side ( p < 0.05). During the static test, average values of body weight distribution on the O and NO limb were 36%BW and 64%BW, respectively. CONCLUSIONS: The patients showed surprisingly similar level of loading on the O limb. The weight bearing on the O limb was lower during static trial than during three-point crutch gait. PMID- 27405883 TI - A natural interomone 2-methyl-2-butenal stimulates feed intake and weight gain in weaned pigs. AB - A novel approach to potentially improve pig growth and welfare is to supplement environments with biologically meaningful odors that are deficient. The post weaning environment lacks maternal odors that may contribute to the often observed post-weaning lag in growth and health challenges. A recently reported rabbit maternal pheromone (2-methyl-2-butenal (2M2B)) may act as an interomone in the pig. The objective of this study was to determine if providing a maternal pheromone/interomone during transport and the post-weaning environment may enhance pig performance. A total of 40 replicated pens were used in a factorial arrangement of two transport olfactory experiences (Control v. 2M2B), two nursery olfactory experiences (Control v. 2M2B) and two sexes (barrow v. gilt). Pig body weight, average daily gain (ADG), average daily feed intake (ADFI) and gain : feed ratio (G : F) were measured and calculated over a 28-day post-weaning period. Pig sex and application of 2M2B during transport had no effect on pig performance. However, pigs that had 2M2B applied to their feeder at weaning had 15% greater feed intake (0.74 v. 0.64+/-0.03 kg/day, P<0.01) and 12% greater ADG (0.27 v. 0.24 kg/day, P<0.05) than control pigs. G : F ratio was not different between treatments. The interomone 2M2B is a novel, safe molecule that can improve pig post-weaning performance. This report highlights a new area of study and a natural class of compounds that can improve pig performance and potentially improve pig welfare. PMID- 27405884 TI - Efficient implementation of constant pH molecular dynamics on modern graphics processors. AB - The treatment of pH sensitive ionization states for titratable residues in proteins is often omitted from molecular dynamics (MD) simulations. While static charge models can answer many questions regarding protein conformational equilibrium and protein-ligand interactions, pH-sensitive phenomena such as acid activated chaperones and amyloidogenic protein aggregation are inaccessible to such models. Constant pH molecular dynamics (CPHMD) coupled with the Generalized Born with a Simple sWitching function (GBSW) implicit solvent model provide an accurate framework for simulating pH sensitive processes in biological systems. Although this combination has demonstrated success in predicting pKa values of protein structures, and in exploring dynamics of ionizable side-chains, its speed has been an impediment to routine application. The recent availability of low cost graphics processing unit (GPU) chipsets with thousands of processing cores, together with the implementation of the accurate GBSW implicit solvent model on those chipsets (Arthur and Brooks, J. Comput. Chem. 2016, 37, 927), provide an opportunity to improve the speed of CPHMD and ionization modeling greatly. Here, we present a first implementation of GPU-enabled CPHMD within the CHARMM-OpenMM simulation package interface. Depending on the system size and nonbonded force cutoff parameters, we find speed increases of between one and three orders of magnitude. Additionally, the algorithm scales better with system size than the CPU-based algorithm, thus allowing for larger systems to be modeled in a cost effective manner. We anticipate that the improved performance of this methodology will open the door for broad-spread application of CPHMD in its modeling pH mediated biological processes. (c) 2016 Wiley Periodicals, Inc. PMID- 27405885 TI - Anti-envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection. AB - Injection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high-risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti-HCV-envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty-two hepatitis C diagnostic antibody- and RNA negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus-neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti-envelope antibodies. In addition to confirming viral exposure, the presence of specific anti-envelope antibodies may be a factor that helps these individuals resist HCV infection. PMID- 27405886 TI - Data Linkage from Clinical to Study Databases via an R Data Warehouse User Interface. Experiences from a Large Clinical Follow-up Study. AB - BACKGROUND: Data that needs to be documented for clinical studies has often been acquired and documented in clinical routine. Usually this data is manually transferred to Case Report Forms (CRF) and/or directly into an electronic data capture (EDC) system. OBJECTIVES: To enhance the documentation process of a large clinical follow-up study targeting patients admitted for acutely decompensated heart failure by accessing the data created during routine and study visits from a hospital information system (HIS) and by transferring it via a data warehouse (DWH) into the study's EDC system. METHODS: This project is based on the clinical DWH developed at the University of Wurzburg. The DWH was extended by several new data domains including data created by the study team itself. An R user interface was developed for the DWH that allows to access its source data in all its detail, to transform data as comprehensively as possible by R into study-specific variables and to support the creation of data and catalog tables. RESULTS: A data flow was established that starts with labeling patients as study patients within the HIS and proceeds with updating the DWH with this label and further data domains at a daily rate. Several study-specific variables were defined using the implemented R user interface of the DWH. This system was then used to export these variables as data tables ready for import into our EDC system. The data tables were then used to initialize the first 296 patients within the EDC system by pseudonym, visit and data values. Afterwards, these records were filled with clinical data on heart failure, vital parameters and time spent on selected wards. CONCLUSIONS: This solution focuses on the comprehensive access and transformation of data for a DWH-EDC system linkage. Using this system in a large clinical study has demonstrated the feasibility of this approach for a study with a complex visit schedule. PMID- 27405887 TI - Investigating poultry trade patterns to guide avian influenza surveillance and control: a case study in Vietnam. AB - Live bird markets are often the focus of surveillance activities monitoring avian influenza viruses (AIV) circulating in poultry. However, in order to ensure a high sensitivity of virus detection and effectiveness of management actions, poultry management practices features influencing AIV dynamics need to be accounted for in the design of surveillance programmes. In order to address this knowledge gap, a cross-sectional survey was conducted through interviews with 791 traders in 18 Vietnamese live bird markets. Markets greatly differed according to the sources from which poultry was obtained, and their connections to other markets through the movements of their traders. These features, which could be informed based on indicators that are easy to measure, suggest that markets could be used as sentinels for monitoring virus strains circulating in specific segments of the poultry production sector. AIV spread within markets was modelled. Due to the high turn-over of poultry, viral amplification was likely to be minimal in most of the largest markets. However, due to the large number of birds being introduced each day, and challenges related to cleaning and disinfection, environmental accumulation of viruses at markets may take place, posing a threat to the poultry production sector and to public health. PMID- 27405889 TI - Controversies in osteoporosis management. PMID- 27405888 TI - Functional conservation and diversification of the soybean maturity gene E1 and its homologs in legumes. AB - Gene regulatory networks involved in flowering time and photoperiodic responses in legumes remain unknown. Although the major maturity gene E1 has been successfully deciphered in soybean, knowledge on the functional conservation of this gene is limited to a certain extent to E1 homologs in legumes. The ectopic expression of Phvul.009G204600 (PvE1L), an E1 homolog from common bean, delayed the onset of flowering in soybean. By contrast, the ectopic expression of Medtr2g058520 (MtE1L) from Medicago truncatula did not affect the flowering of soybean. Characterization of the late-flowering mte1l mutant indicated that MtE1L promoted flowering in Medicago truncatula. Moreover, all transgenic E1, PvE1L and MtE1L soybean lines exhibited phenotypic changes in terms of plant height. Transgenic E1 or PvE1L plants were taller than the wild-type, whereas transgenic MtE1L plants produced dwarf phenotype with few nodes and short internode. Thus, functional conservation and diversification of E1 family genes from legumes in the regulation of flowering and plant growth may be associated with lineage specification and genomic duplication. PMID- 27405891 TI - Creating the optimal workspace for hospital staff using human centred design. AB - We were tasked with creating best possible non-clinical workspace solutions for approximately 450 hospital staff across 11 departments encompassing medical, nursing, allied health, administrative and other support staff. We used a Human Centred Design process, involving 'Hear, Create and Deliver' stages. We used observations, contextual enquiry and role-specific workshops to understand needs, key interactions and drivers of behaviour. Co-design workshops were then used to explore and prototype-test concepts for the final design. With extensive employee engagement and design process expertise, an innovative solution was created that focussed on meeting the functional workspace needs of a diverse group of staff requiring a range of different spaces, incorporating space constraints and equity. This project demonstrated the strength of engaging employees in an expert led Human-Centred Design process. We believe this is a successful blueprint process for other institutions to embrace when facing similar workspace design challenges. PMID- 27405890 TI - Young onset dementia. AB - Young onset dementia (YOD), where symptoms of dementia have an onset before the age of 65, has become more prominent due to the population increase from the Baby Boomer generation. This clinical perspective examines key issues in the assessment, diagnosis and management of YOD. Challenges in the assessment and diagnosis of YOD are partly due to the diverse range of types of YOD, where degenerative dementias are less common and secondary dementias more common than in late onset dementia. Early symptoms are broad and include depression, behavioural change, neurological disorders, systemic disorders and mild cognitive impairment (MCI). Perceived diagnostic delay may result in frustration and distress in people with YOD and their families. Chronic depression and MCI are associated with longer time to diagnosis, and in these situations, clinicians need to establish appropriate review processes and communicate clearly. A diagnosis of YOD may have marked consequences for a younger person, including early retirement, financial impacts and the psychological challenge of coming to grips with cognitive decline. Partners, children and other supporters often have unmet needs, feel burdened by care and are at high risk of physical and emotional consequences. Concerns about the heritability of dementia may add to family distress. Recent community service developments in Australia for YOD are outlined and the challenges of residential care described. PMID- 27405893 TI - The use of low-dose sodium valproate in the management of neuropathic pain: illustrative case series. AB - Anti-epileptic drugs are commonly used in the management of neuropathic pain. Sodium valproate, however, is an anti-epileptic drug that is not commonly used. We report four patients with neuropathic pain who responded very well to the initiation of low-dose oral sodium valproate. Low-dose sodium valproate may have a role in managing neuropathic pain, especially when other first-line agents are unsuccessful or relatively contraindicated. PMID- 27405892 TI - Elevated total serum immunoglobulin E (>1000 IU/mL): implications? AB - Atopic eczema, allergic broncho-pulmonary aspergillosis, helminthic infections and rare primary immunodeficiencies are known to elevate total serum immunoglobulin E (IgE) above 1000 IU/mL. However, of 352 patients with IgE >1000 IU/mL seen in our hospital over a 5-year period, less than 50% had these conditions. Markedly elevated IgE levels in the rest of the patients were associated with asthma, allergic rhinitis and food allergy, instances where the test is of limited diagnostic utility. PMID- 27405895 TI - Persistent left atrial thrombus on treatment with rivaroxaban and subsequent resolution after warfarin therapy. PMID- 27405894 TI - Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience. AB - Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. PMID- 27405896 TI - Transient secondary hyperparathyroidism in acute kidney injury. PMID- 27405897 TI - Menstrual anaphylactoid reactions and presumed systemic mast cell activation syndrome. PMID- 27405898 TI - Coeliac disease presenting as apparent haemochromatosis. PMID- 27405899 TI - Associated factors with atherosclerosis in hepatitis C infection. PMID- 27405900 TI - Author reply. PMID- 27405901 TI - Acupuncture is not a unique explanation for functional magnetic resonance imaging finding. PMID- 27405902 TI - The application experience of all-around nursing care in infantile febrile convulsion. AB - BACKGROUND: To analyze the value of all-around nursing care for infantile febrile convulsion. METHODS: Ninety-eight cases diagnosed with infantile febrile convulsion from February 2013 to October 2014 were selected to participate in this study. This study was approved by the hospital's ethics committee and received consent from the patients as well as their families. The patients were divided into a control group (n=48 cases) and an observation group (n=50 cases). Patients in both groups were offered anticonvulsants. The control group was offered general nursing care while the observation group was offered all-around nursing care. We compared and analyzed the nursing care in both groups. RESULTS: The body temperature recovery and convulsion control time in the observation group were lower than the control group. Remarkably, the convulsion control rate was higher than the control group. The hospital stays were lower in the observation group compared to the control group (P<0.05). The patients' serum potassium, serum sodium levels and blood glucose before nursing care were all in the normal range. However, the serum potassium and serum sodium levels in the control group were lower, and the blood glucose level was higher than previous. After nursing care, the serum potassium and serum sodium levels in the observation group were higher than the control group. The blood glucose level was lower than the control group (P<0.05). The nursing satisfaction in the observation group was higher than the control group. The convulsion recurrence rate was lower in the observation group compared to the control group (P<0.05). CONCLUSIONS: The combination of all-around nursing care and anticonvulsants can improve the occurrence and duration of infantile febrile convulsion. PMID- 27405903 TI - Association between the lactate/albumin ratio and mortality in pediatric septic shock patients with underlying chronic disease: retrospective pilot study. AB - BACKGROUND: We aimed to evaluate the ability of the lactate/albumin ratio to predict mortality in pediatric septic shock patients. METHODS: Retrospective analysis of the medical records of a pediatric intensive care unit. The study cohort comprised 90 pediatric septic shock patients admitted from February 2012 to May 2015. RESULTS: The serum lactate and albumin levels and lactate/albumin ratio were compared between survivors and non-survivors. We assessed whether the lactate/albumin ratio could be used to predict mortality. The 28-day hospital mortality was 26.7%(24/90). The lactate level was higher(2.5 +/- 2.2 vs 8.1 +/- 5.1 mmol/L, p<0.001) and the albumin level was lower(2.9 +/- 0.5 vs 2.7 +/- 0.5 mg/dL, p=0.063) in non-survivors than in survivors. The lactate/albumin ratio was 0.9 +/- 0.8 in survivors and 3.2 +/- 2.4 in non-survivors(p<0.001). According to the area under the receiver operating characteristic curve (AUC), the lactate/albumin ratio showed good discriminatory power for predicting mortality (AUC = 0.867). A lactate/albumin ratio exceeding 1.016 led to an 7.636-fold increase in mortality. CONCLUSIONS: The lactate/albumin ratio is a useful predictor of mortality in pediatric septic shock patients. PMID- 27405904 TI - Morbidity and mortality of preterm infants less than 26 weeks of gestational age. AB - BACKGROUND: Extreme preterm infants have a high risk of morbidity and mortality. Newborns delivered between 23+0 and 25+6 weeks, are considered to be in the "gray zone" and have uncertain prognosis. For these children medical decision-making becomes complex and controversial. The present study intends to evaluate the neonatal morbidity and mortality of preterm infants born between 23 weeks and 25+6 weeks of gestational age. METHODS: A retrospective study was conducted including all inborn preterm infants, with a gestational age between 23+0 and 25+6 weeks, admitted to a level IIIC NICU, between 1st January, 1996 and 31th December, 2014. RESULTS: A total of 72 preterm neonates were included, 18.1% had a full cycle of antenatal steroids. The most frequent major morbidities were RDS (95.4%), patent ductus arteriosus (81.3%), sepsis (55.7%, being 19.7% early sepsis, and 36.1% late sepsis), intraventricular hemorrhage (34.4%), retinopathy of prematurity (21.9%) and necrotizing enterocolitis (10.9%). Fifty-four (75%) children died. The only factor adjusted to age associated with high mortality founded was hypotension (OR=4.99, p<0.019). Morbidity at discharge was: severe bronchopulmonary dysplasia (77.8%), retinopathy of prematurity (72.2%), intraventricular hemorrhage (16.7%), cystic periventricular leukomalacia (11.1%) and necrotizing enterocolitis' sequelae (5.6%). CONCLUSION: The survival rate was 25% and a high morbidity at discharge was observed, which leave us with the huge responsibility to improve this result in a near future. Extreme prematurity is still a very controversial and complex issue and particular challenge for neonatologists. The use of antenatal steroid in the more immature preterm infants should be encouraged. PMID- 27405905 TI - We Are What We Eat. PMID- 27405906 TI - Nutritional Effects on Central Serotonergic Activity: A Hypothesis on the Unconscious Self-manipulation of Mood by Food Intake and Dietary Selection. AB - Fasting seems to stimulate the output of the serotonergic system at least as efficiently as a carbohydrate-or a fat-rich meal. Food-intake mediated effects on mood may become incorporated into a behavioural paradigm related to unconscious behaviour and may funnel vulnerable individuals into a vicious circle of eating disorders. Are carbohydrate craving-induced obesity and anorexia nervosa diseases of addiction? PMID- 27405907 TI - Dehydroepiandrosterone: A Nutritional Supplement with Actions in the Central Nervous System. AB - Because of changes wrought by the U.S. Dietary Supplement Health and Education Act of 1994, DHEA (dehydroepiandrosterone) is now available to the general population as a dietary supplement. Although advertising of any health benefit is restricted, many people take it for purported salutary effects of age-related processes. One of these suspected benefits is the delay of Alzheimer's disease. This review evaluates the literature derived from both animal and human trials that leads people to believe DHEA may exert such an effect. It will show that DHEA is active in the central nervous system when given exogenously, is made in the central nervous system of laboratory animals and may have a role in regulating normal physiologic processes. Possible cellular mechanisms of action are described. DHEA may have particular effects on learning and memory in test animals, but there is only sparse data in humans where observations are indirect and poorly controlled. Still, it is concluded that the data is compelling enough to warrant further research, although it is premature to suggest a safe dosing schedule for humans who may want to try this steroid hormone. PMID- 27405908 TI - Promising Psychotherapeutic Effects of the Natural Sugar: Myo-Inositol. AB - Myo-inositol is a common six-carbon sugar with unique biochemical and psychotherapeutic properties. It is involved in neuronal signaling and osmoregulation, and has been shown to be therapeutic in initial studies of depression, panic disorder, and obsessive-compulsive disorder. The inositol signaling system is a post-receptor second messenger system found in many cells, and is similar to the cAMP system. Myo-inositol exists in the free form, or as a component of membrane inositol phospholipids which are present largely on the inner leaflet of the plasma membrane. Inositol phospholipids, particularly phosphatidylinositol 4,5-bis-phosphate (PIP2), are linked to a number of brain receptor signaling systems including serotonergic, muscarinic, adrenergic, histaminergic, cholecystokinin, tachykinins, metabotropic, neurotensin, platelet activating factor, and others. With receptor stimulation, the signal is transmitted through a series of other proteins. Activation of a GTP-binding protein (Gq), in turn activates plasma membrane phospholipase C releasing the second messenger, myo-inositol 1,4,5-trisphosphate (InsP3), into the cytosol. InsP3 then causes release of free calcium from endoplasmic reticulum into the cytosol, which then activates a number of calcium-sensitive enzymes and receptors. Myo-inositol is made available to the brain through three sources: (i) receptor stimulation (salvage pathway), (ii) de novo production, and (iii) dietary intake. Initial clinical studies have shown that myo-inositol has psychoactive effects, and is effective in the treatment of specific mood and anxiety disorders. Recent preliminary clinical studies have suggested the fascinating possibility that myo-inositol has psychoactive effects, and may be effective in the treatment specific mood and anxiety disorders. Further clinical studies are required using larger groups of patients before definitive conclusions can be drawn upon the use of myo-inositol as a potential psychoactive compound. Myo-inositol as a natural medication increases interest in this newly emerging area of nutritional neuroscience. PMID- 27405909 TI - NADPH-Diaphorase Containing Neurons and Biocytin-labelled Axon Terminals in the Visual Cortex of Adult Rats Malnourished During Development. AB - This is the first report of the effects of malnutrition during brain development on biocytin-labelled axon terminals and histochemical pattern of NADPH-diaphorase (NADPH-d)-containing neurons in area 17 of the adult rat. Wistar rats (n = 6) were submitted early in life (from gestation up to 42 days of age) to a multideficient diet (the 'regional basic diet' (RBD) of low-income human populations of north-east Brazil, containing only 8% protein). From day 43 up to adulthood (135-212 days), they were switched to a commercial laboratory chow diet (Purina do Brasil Ltda), with 22% protein. These animals were compared to control rats (n = 11), fed the laboratory chow diet until adulthood. The brains of four adult malnourished and five controls were processed according to the indirect method of the malic enzyme to reveal NADPH-d-containing neurons. Five other adult subjects (three controls and two malnourished) received iontophoretic injections of the tracer biocytin in area 17and were processed according to the glucose oxidase-DAB-nickel protocol in order to visualize axon terminals filled with biocytin. Three other control rats were processed for both techniques. In these last brains, no double-labelled cells could be found, suggesting that the NADPH-d containing-neurons and the biocytin-labelled ones belong to different groups of cells, in area 17. The appendages of the NADPH-d-positive cells showed minor qualitative and quantitative differences between undernourished and control rats. The soma area of these cells was reduced in the white matter of malnourished rats, as compared to the controls (468.6 +/- 54.3 MUm(2); n = 4 and 515.4 +/- 30.5 MUm(2);n = 8, respectively; p < 0.05). The cell density (cells/mm(2)) was greater in the malnourished group than in the control, both at the grey matter (16.6 +/- 4.4; n = 4 and 11.3 +/- 4.3; n = 8, respectively; p < 0.05) and at the white matter (55.9 +/- 15.7; n = 4 and 24.4 +/- 8.5; n = 8; p < 0.005). The number of potential synaptic sites in the biocytin-labelled axon terminals was reduced as compared to the control (126 +/- 33 boutons/mm, n = 32 and 160 +/- 37; n = 30, respectively; p < 0.01). The results indicate that the rat area 17 is affected differently by early malnutrition, regarding biocytin-labelled axon terminals, on the one hand, and NADPH-d-containing neurons, on the other. Concerning these last cells, the data also suggest that they are less sensitive to the injury represented by early malnutrition. PMID- 27405910 TI - A Saturated-Fat Diet during Development Alters Dendritic Growth in Mouse Brain. AB - The objective of this study was to determine whether an essential fatty acid (EFA)-deficient diet (saturated fat) fed during development would alter the pattern of dendritic growth in pyramidal neurons of mouse occipital cortex. Pregnant and lactating mice were fed either a saturated fat or control diet throughout pregnancy and lactation. At weaning, one female was selected randomly from each litter, and these animals were maintained on their respective diets and reared in an enriched environment for eight weeks. Following this, their brains were processed histologically using a modified Golgi-Cox method, and patterns of dendritic growth were analysed in occipital pyramidal cells. A Sholl concentric circle analysis indicated that, for basilar dendrites, starting at a distance of 62.5 MUm, animals fed saturated fat had fewer crossings than controls, which is indicative of either shorter dendrites or of less dendritic branching. Although the analysis of branching order was not significant, the trend seen in these data supports less branching in the saturated fat group, particularly of third- and fourth-order dendrites. Similar effects were seen in the apical dendrites, although to a lesser extent. Covariance analysis indicated that these effects could not be accounted for by the smaller brains in the EFA-deficient group. They can therefore be considered preliminary support for an effect of EFA on the pattern of dendritic development. PMID- 27405911 TI - Opioid Peptides, Adrenocorticotrophic Hormone and Dietary Copper Intake in Humans. AB - Copper plays an important role in cardiac and brain function possibly through endocrine and neuroendocrine systems. The syndrome of copper deficiency is worsened by dietary fructose and other trace metals such as zinc. We investigated the effect of a low copper diet on plasma opioid peptides in 11 healthy young volunteers who were fed foods low in copper but adequate in all other nutrients. The study was divided into three dietary periods. Copper was added to the diet so that the diet contained 0.66 mg/day for 24 days (marginal Cu), 0.38 mg/day for 42 days (low Cu) and 2.49 mg/day for 24 days (adequate Cu). The indices of copper status, ceruloplasmin and plasma copper concentrations, declined and were significantly lower (p < 0.05) at the end of the low Cu period than at the beginning of the study and the end of the marginal Cu period. They increased significantly at the end of the adequate Cu diet to the levels of the marginal Cu diet. Plasma beta-endorphin (BEN), Leu-enkephalin (LE), Met-enkephalin (ME) and Adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay at the beginning of the study and at the end of each dietary period. No significant differences were observed in BEN, LE or ME during any of the periods. There were only small increases in LE and ME at the end of marginal and low copper diet periods and no significant changes were observed on copper repletion. Plasma ACTH was significantly lower at the end of low copper compared to baseline value but was not lower after marginal copper. Copper repletion had no significant effect on ACTH. The data show that plasma opioid peptides did not respond significantly to differential copper intake. PMID- 27405912 TI - Dietary Protein and Central Monoamine Concentrations in the Rat. AB - In a previous report we demonstrated that rats that consumed a high-protein diet (HP; 50% casein) for 36 weeks were hyperactive and hyperresponsive to nociceptive stimuli, compared to rats that consumed normal (NP; 20% casein) or low-protein (LP; 8% casein) diets. In addition, we have also previously, reported that dopamine concentrations in the nigrostriatal system of the rats were decreased and increased, respectively, with a decrease and increase in dietary protein. In the present study, rats were maintained on the HP, NP and LP diets and regional changes in the concentrations of norepinephrine (NE) and serotonin (5 hydroxytryptamine, 5-HT) were assessed. Concentrations of 5-HT in the medial raphe, dorsal raphe, and several of their target tissues, revealed no consistent effect of manipulating dietary protein over the range of 5-HT levels measured. NE concentrations in most of the brain regions innervated by neurons of the locus coeruleus and lateral tegmentum showed no significant differences among the diet groups. However, NE concentrations in the parietal cortex were significantly increased in rats that consumed the HP diet. The present study indicates that the brain NE pathways, particularly that innervating the parietal cortex, is susceptible to dietary protein manipulation. PMID- 27405914 TI - The Use of Ginseng as an Adjunct in Treatment-Resistant Depression. AB - The treatment of depression has evolved over the past several years since the evolution of tricyclic antidepressants (TCAs) to the serotonin selective reuptake inhibitors (SSRIs). However, some patients are resistant to various medications, and various adjunctive medications have been added to the original medication, to promote a therapeutic response. This case report describes a woman, with a long history of treatment-resistant depression, who was treated with a combination of an SSRI and ginseng. PMID- 27405913 TI - Relationship between Hypothalamic-Pituitary-Adrenal Axis Function and Leptin Release. AB - The activation of sympathetic activity which is related to hypothalamic corticotropin-releasing hormone (CRH) release may modulate ob gene expression in vivo. In the present studies, we determined changes in circulating leptin concentrations by modulating sympathetic activity by adrenalectomy, corticosterone supplement, hypothalamic CRH infusion and starvation in male Wistar rats. Bilateral adrenalectomy significantly inhibited serum leptin concentrations and the continuous supplement of corticosterone by silastic tube restored the reduction of serum leptin concentrations in adrenalectomized rats. Intracerebro-ventricular infusion of 2MUg recombinant rat CRH significantly decreased serum leptin concentrations at 2 hours after the infusion. In addition, 24-hour starvation significantly decreased retroperitoneal adipose tissue ob gene expression, measured by the reverse transcription-polymerase chain reaction (RT PCR) method, and serum leptin concentrations. The data obtained herein indicated that the activation of CRH-ACTH axis by adrenalectomy, intracerebro-ventricular CRH infusion and starvation inhibits leptin production from adipose tissues and the reduced production of the anorexigenic message from adipose tissues may play a role in maintaining homeostasis in vivo by the disinhibition of hypothalamic feeding centers which is inhibited by hypothalamic CRH-containing neurons. PMID- 27405915 TI - How to Calculate Sample Size for an Experiment: A Case-Based Description. AB - This is the first in a series of articles devoted to a simplified description of experimental design, statistical analysis, and interpretation, using actual laboratory data as examples. The present article deals with sample size calculation for a single factor experiment and for a repeated measures design. PMID- 27405916 TI - alpha,alpha-Dicyanoolefins: versatile substrates in organocatalytic asymmetric transformations. AB - alpha,alpha-Dicyanoolefins have emerged as versatile reactants, finding use as vinylogous nucleophiles, Michael acceptors and dienophiles in a variety of organic reactions. In the last few years, the reactivity of alpha,alpha dicyanoolefins has been explored in various asymmetric transformations catalyzed by organocatalysts. In this review, we are presenting the recent advances in asymmetric organocatalytic transformations involving alpha,alpha-dicyanoolefins. PMID- 27405917 TI - Toxicity of serum albumin on microglia upon seeding effect of amyloid peptide. AB - We demonstrate in vitro cross-seeding of bovine serum albumin (BSA) in the presence of Abeta25-35 and their cytotoxic effects on microglial cells. To investigate the cross-seeding of BSA in the presence of Abeta25-35 fibrils, we examined how Abeta25-35 fibrils can function as seeds to trigger and accelerate BSA fibrillogenesis using ThT, intrinsic fluorescence, ANS fluorescence and transmission electron microscopy (TEM). Moreover, the effects of these fibrils on microglial viability were measured using MTT and Annexin V/propidium iodide (PI) staining. Although Abeta25-35 is toxic against microglia, it acted as seed and affected the aggregation pathway and accelerated the fibrillogenesis of BSA in vitro, resulted in an enhanced cytotoxic effect in comparison with Abeta25-35 or BSA alone. These observations thought to be helpful to understand the molecular mechanism of enhanced toxicity due to the coexistence of the aggregation prone proteins/peptides,. then cross-seeding effect on microglial cells that may involve in neurodegenerative diseases such as Alzheimer's disease (AD). PMID- 27405918 TI - Challenges in Catalytic Hydrophosphination. AB - Despite significant advances, metal-catalyzed hydrophosphination has ample room for discovery, growth, and development. Many of the key successes in metal catalyzed hydrophosphination over the last decade have indicated what is needed and what is yet to come. Reactivity that is absent from the literature also speaks to the challenges in catalytic hydrophosphination. This Concept article discusses and highlights recent developments that address the ongoing challenges, and identifies areas in metal-catalyzed hydrophosphination that are underdeveloped. Advances in product selectivity, catalyst design, and both unsaturated and phosphine substrates illustrate the ongoing development of the field. Like all catalytic transformations, the benefits are realized through catalyst, ligand, and conditions, and consideration of those features are the route to a yet more efficient and broadly applicable reaction. PMID- 27405919 TI - Investigations of mammary and uterine blood flow in relation to milk yield, postpartum disease, and pregnancy result in dairy cows. AB - The objective was to determine the blood flow variables in the uterine arteries and the pudendoepigastric trunks, which supply the mammary gland, and relate these variables to the occurrence of uterine disease, milk yield, and pregnancy result. To achieve this, 119 multiparous German Holstein cows were examined using color Doppler sonography once during the dry period and on Days 7, 14, 28, 42, 56, 66, 76, 86, and 96 postpartum (pp). Cows with retained fetal membranes or metritis had a higher blood flow volume and time-averaged maximum velocity and a lower pulsatility index in the uterine arteries on Days 7, 14 and 28 pp (P < 0.05). Milk yield was correlated with blood flow volume in the pudendoepigastric trunks on examination Days 7 to 96 pp with the exception of Day 76 (P < 0.05), and with time-averaged maximum velocity on Days 7 and 14 pp (P < 0.05). The pulsatility index was greater in the left pudendoepigastric trunk on examination Days 7 to 76 pp than in the right pudendoepigastric trunk (P < 0.05). Milk yield did not affect pregnancy result and was not related to uterine perfusion. Increased uterine perfusion in cows with retained fetal membrane and metritis may be due to increased uterine size attributable to delayed involution. High mammary perfusion in high-yielding cows is due to an increased demand for nutrients and oxygen. Color Doppler sonography is a useful method for the investigation of the effect of uterine disease on uterine blood flow and of the effect of milk yield on mammary perfusion. PMID- 27405920 TI - Clinicopathological study of ovarian carcinoid tumours. AB - OBJECTIVE: To describe the clinical features, treatment, clinical course and survival rates of women diagnosed with ovarian carcinoid tumours. METHODS: A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumours who were managed by the Queensland Centre for Gynaecological Cancer from 1982 to 2015. RESULTS: Eighteen patients were identified with ovarian carcinoid tumours over the 32 years of the study period. Of the 18 patients, 14 were diagnosed with stage 1 disease, two were diagnosed with stage 3 disease and two were diagnosed with stage 4 disease. Carcinoid syndrome was present in two patients. All patients underwent surgical management. Follow-up strategies varied for early stage disease, but no patient with early stage disease received any adjuvant treatment and no patient developed recurrent disease. Patients with advanced stage disease were treated with cytoreductive surgery and chemotherapy. The five year survival was 100% for stage 1 disease, and 25% for stages 3 and 4 disease. CONCLUSIONS: The vast majority of carcinoid tumours are diagnosed as an incidental finding. Prognosis for early stage disease is excellent, whether conservative or more extensive surgery with staging was performed, and intensive follow up did not influence survival. Optimal treatment for advanced disease remains unknown and requires further study. PMID- 27405921 TI - Toward the Facile and Ecofriendly Fabrication of Quantum Dot-Sensitized Solar Cells via Thiol Coadsorbent Assistance. AB - This paper reports a facile and environmentally friendly approach to the preparation of highly efficient quantum dot-sensitized solar cells (QDSSCs) based on a combination of aqueous CuInS2 quantum dots (QDs) and thiol coadsorbents. The photovoltaic properties of the QDSSCs were found to be dependent on the type and concentration of the thiol coadsorbent. The incorporation of thiol coadsorbents results in improved JSC and VOC because (1) they provide disulfide reductants during the QD sensitization process and (2) the coadsorbent molecules are anchored on the TiO2 surface, thus affecting the movement of the conduction band of TiO2. To the best of the our knowledge, this is the first demonstrated use of various thiol coadsorbents as reducing agents in the fabrication of high efficiency QDSSCs. CuInS2 QDSSCs fabricated with the assistance of thioglycolic acid coadsorbents exhibited efficiencies as high as 5.90%, which is 20 times higher than that of the control device without thiol coadsorbents (0.29%). In addition, the photovoltaic properties of a device fabricated using the colloidal CuInS2 QDs coated with different bifunctional linkers were investigated for comparison. The versatility of this facile fabrication process was demonstrated in the preparation of solar cells sensitized with aqueous AgInS2 or CdSeTe QDs. The AgInS2 QDSSC showed a conversion efficiency of 2.72%, which is the highest reported for Ag-based metal sulfides QDSSCs thus far. PMID- 27405923 TI - Integrative analysis of pathogen replication and spread: zooming into increasing complexity. PMID- 27405922 TI - A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat. AB - Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and Treg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and Treg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the Treg cell fraction was lower (p < 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more Treg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger. PMID- 27405924 TI - The importance of obstructive sleep apnea screening in driving license application procedures. PMID- 27405925 TI - Dietary fatty acid composition is sensed by the NLRP3 inflammasome: omega-3 fatty acid (DHA) prevents NLRP3 activation in human macrophages. AB - The Nod-like receptor protein 3 (NLRP3) inflammasome is considered to be a pivotal host platform responsible for sensing of exogenous and endogenous danger signals, including those generated as a result of metabolic dysregulation, and for the subsequent, IL-1beta-mediated orchestration of inflammatory and innate immunity responses. In this way, although the molecular link between diet-induced obesity and inflammasome activation is still unclear, free fatty acids (FFA) have been proposed as a triggering event. We report that dietary fatty acid (FA) composition is sensed by the NLRP3 inflammasome in human macrophages. For this purpose, we have analysed three roles of FA supplementation: as a priming signal for ATP-activated macrophages, in determining where the administration of dietary FAs interferes with LPS-mediated inflammasome activation and by inducing inflammasome activation per se. In this study, we confirm that saturated (SFAs) activated the NLRP3 inflammasome and stimulated the secretion of the IL-1beta cytokine, while PUFAs were mainly inhibitors. Moreover, in general, DHA (n-3 PUFA) was more effective in preventing inflammasome activation than arachidonic acid (n-6 PUFA). PMID- 27405926 TI - The CPR outcomes of online medical video instruction versus on-scene medical instruction using simulated cardiac arrest stations. AB - BACKGROUND: Non-traumatic cardiac arrest is a fatal emergency condition. Its survival rate and outcomes may be better with quick and effective cardiopulmonary resuscitation (CPR). Telemedicine such as telephone or real time video has been shown to improve chest compression procedures. There are limited data on the effects of telemedicine in cardiac arrest situations in the literature particularly in Asian settings. METHODS: This study was conducted by using two simulated cardiac arrest stations during the 2014 annual Thai national conference in emergency medicine. These two stations, nos. 5 and 11, were a part of the conference activity called "EMS rally" which was comprised of 14 stations. Both stations were shockable and out-of-hospital cardiac arrest situations; station 5 was online instructed, while station 11 was on-scene instructed. There were 14 representative teams from each province from all over Thailand who participated in the rally. Each team had one physician, one nurse, and two emergency medicine technicians. Eight CPR outcomes were evaluated and compared between the online versus on-scene situations. RESULTS: There were 14 representative teams that participated in the study; a total of 14 physicians, 14 nurses, and 28 emergency medicine technicians. The average ages of participants in all three occupations were between the second and third decade of life. The percentages of participants with more than 3 years in ambulance experience was 7.1, 64.3, and 53.6 % in the physicians, nurses, and EMTs groups. The median times of all outcomes were significantly longer in the online group than the on-scene group including times from start to chest compression (total 102 vs 36 s), total times from the start to VT/VF detection (187 vs 99 s); times from VT/VF detection to the first defibrillation (57 vs 28 s); and times from the start of adrenaline injection (282 vs 165 s). The percentages of using amiodarone (21.43 % vs 57.14 %; p value < 0.001), establishment of a definitive airway (35.71 % vs 100 %; p value 0.003), and correct detections of pulseless electrical activity (PEA) (28.57 % vs 100 %; p value < 0.001) were significantly lower in the online group than the on-scene group. The high quality CPR outcomes between the online group and on-scene group were comparable. CONCLUSIONS: The online medical instruction may have worse CPR outcomes compared with on-scene medical instruction in shockable, simulated CPR scenarios. Further studies are needed to confirm these results. PMID- 27405927 TI - Comparison of single and dual growing rods in the treatment of early onset scoliosis: a meta-analysis. AB - BACKGROUND: The growing rod technique was applied in the treatment of early onset scoliosis (EOS) with promising outcomes and many complications at the same time. We reviewed data from literatures to compare the results of single growing rods with dual growing rods to achieve a clear understanding of this technique. METHODS: PubMed, Embase, MEDLINE, ScienceDirect, CNKI, Wanfang Data, and CQVIP were searched electronically until March 2016 using "growing rod" and "early onset scoliosis" as major search terms. Also, we manually searched other relevant conference proceedings. Two reviewers independently finished methodological quality assessment, data extraction, and calculations. RESULTS: Six retrospective trials were adopted in data analysis including 126 and 119 patients in the single and dual rod groups, respectively. Significantly better coronal correction rates were observed immediately after the initial operation (MD = -14.67; 95 % CI 20.97 to -8.37; P < 0.01; I (2) = 0 %) and at the final follow-up (MD = -23.70; 95 % CI -45.87 to -1.52; P = 0.04; I (2) = 82 %) in the dual rod group. Similarly, better lengthening of the T1-S1 height occurred in the dual rod group immediately after the initial operation (MD = -1.74; 95 % CI -2.62 to -0.85; P < 0.01; I (2) = 0 %) and at final follow-up (MD = -3.8; 95 % CI -5.56 to -2.04; P < 0.001; I (2) = 36 %). There were more complications about the implant in the single rod group, while wound problems were common in the other group. CONCLUSIONS: The data of the current meta-analysis showed advantages in the coronal correction rate and lengthening by dual growing rods with fewer implant related complications and more wound complications. PMID- 27405928 TI - Virus like particle-based vaccines against emerging infectious disease viruses. AB - Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families. PMID- 27405929 TI - Monoclonal antibody-based serological methods for detecting Citrus tristeza virus in citrus groves. AB - Citrus tristeza virus (CTV) is one of the most economically important citrus viruses and harms the citrus industry worldwide. To develop reliable and effective serological detection assays of CTV, the major capsid protein (CP) gene of CTV was expressed in Escherichia coli BL21 (DE3) using the expression vector pET-28a and purified through Ni+-NTA affinity chromatography. The recombinant protein was used to immunize BALB/c mice. Four hybridoma cell lines (14B10, 14H11, 20D5, and 20G12) secreting monoclonal antibodies (MAbs) against CTV were obtained through conventional hybridoma technology. The titers of MAb-containing ascitic fluids secreted by the four hybridoma lines ranged from 10(-6) to 10(-7) in indirect enzyme-linked immunosorbent assay (ELISA). Western blots showed that all four MAbs could specifically react with CTV CP. Using the prepared MAbs, dot ELISA, Tissue print-ELISA, and triple antibody sandwich (TAS)-ELISA were developed to detect CTV in tree nurseries and epidemiological studies. The developed dot-ELISA and TAS-ELISA methods could detect CTV in crude extracts of infected citrus leaves with dilutions of 1:2560 and 1:10, 240 (w/v, g/mL), respectively. Tissue print-ELISA was particularly useful for large-scale field sample detection, mainly owing to its simplicity and lack of sample preparation requirements. The field survey revealed that CTV is prevalent on citrus trees in the Chongqing Municipality, Jiangxi Province, and Zhejiang Province of China. The coincidence rate of serological and RT-PCR test results reached more than 99.5%. The prepared MAbs against CTV and established sensitive and specific serological assays have a significant role in the detection and prevention and control of CTV in our country. PMID- 27405931 TI - Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis. AB - BACKGROUND: Silibinin, a biologically active compound of milk thistle, has chemopreventive effects on cancer cell lines. Recently it was reported that silibinin inhibited tumor growth through activation of the apoptotic signaling pathway. Although various evidences showed multiple signaling pathways of silibinin in apoptosis, there were no reports to address the clear mechanism of ROS-mediated pathway in prostate cancer PC-3 cells. Several studies suggested that reactive oxygen species (ROS) play an important role in various signaling cascades, but the primary source of ROS was currently unclear. METHODS: The effect of silibinin was investigated on cell growth of prostate cell lines by MTT assay. We examined whether silibinin induced apoptosis through production of ROS using flow cytometry. Expression of apoptosis-, endoplasmic reticulum (ER) related protein and gene were determined by western blotting and RT-PCR, respectively. RESULTS: Results showed that silibinin triggered mitochondrial ROS production through NOX4 expression and finally led to induce apoptosis. In addition, mitochondrial ROS caused ER stress through disruption of Ca(2+) homeostasis. Co-treatment of ROS inhibitor reduced the silibinin-induced apoptosis through the inhibition of NOX4 expression, resulting in reduction of both Ca(2+) level and ER stress response. CONCLUSIONS: Taken together, silibinin induced mitochondrial ROS-dependent apoptosis through NOX4, which is associated with disruption of Ca(2+) homeostasis and ER stress response. Therefore, the regulation of NOX4, mitochondrial ROS producer, could be a potential target for the treatment of prostate cancer. PMID- 27405930 TI - Highly pathogenic avian influenza H5N1 Clade 2.3.2.1c virus in migratory birds, 2014-2015. AB - A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015. Based on the genetic and phylogenetic analyses, the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA, a H9N2-derived PB2 gene and the other six genes of Asian H5N1 origin. The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain (A/Alberta/01/2014). Further analysis showed that similar viruses have been circulating in wild birds in China, Russia, Dubai (Western Asia), Bulgaria and Romania (Europe), as well as domestic poultry in some regions of Africa. The affected areas include the Central Asian, East Asian Australasian, West Asian-East African, and Black Sea/Mediterranean flyways. These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds, thus posing a serious threat to wild birds and potentially humans. PMID- 27405932 TI - The RNA-binding protein repertoire of Arabidopsis thaliana. AB - RNA-binding proteins (RBPs) have essential roles in determining the fate of RNA from synthesis to decay and have been studied on a protein-by-protein basis, or computationally based on a number of well-characterised RNA-binding domains. Recently, high-throughput methods enabled the capture of mammalian RNA-binding proteomes. To gain insight into the role of Arabidopsis thaliana RBPs at the systems level, we have employed interactome capture techniques using cells from different ecotypes grown in cultures and leaves. In vivo UV-crosslinking of RNA to RBPs, oligo(dT) capture and mass spectrometry yielded 1,145 different proteins including 550 RBPs that either belong to the functional category 'RNA-binding', have known RNA-binding domains or have orthologs identified in mammals, C. elegans, or S. cerevisiae in addition to 595 novel candidate RBPs. We noted specific subsets of RBPs in cultured cells and leaves and a comparison of Arabidopsis, mammalian, C. elegans, and S. cerevisiae RBPs reveals a common set of proteins with a role in intermediate metabolism, as well as distinct differences suggesting that RBPs are also species and tissue specific. This study provides a foundation for studies that will advance our understanding of the biological significance of RBPs in plant developmental and stimulus specific responses. PMID- 27405933 TI - Characteristics of Traditional Chinese Medicine Use in Pediatric Cancer Patients: A Nationwide, Retrospective, Taiwanese-Registry, Population-Based Study. AB - BACKGROUND: Large-scale surveys of complementary traditional Chinese medicine (TCM) use in pediatric cancer patients are lacking. The aim of our study was to investigate the use of TCM in pediatric cancer patients. METHODS: We analyzed cancer patients younger than 18 years (n = 12 965) who were registered in the National Health Insurance Research Database in Taiwan between 2001 and 2011. Patients were categorized into TCM or non-TCM users based on their use of TCM. RESULTS: In Taiwan, 8086 (62.4%) children with cancer sought TCM treatment at some point. Children in older age groups, including school-aged children and adolescents, were more likely to use TCM. There was no significant difference in the distributions of gender and urbanization. The 3 most common diseases for which TCM users visited the clinic were neoplasm (33.2%), respiratory system disease (32.9%), and infectious disease (8.86%). The most commonly utilized TCM therapy was Chinese herbal remedies. Patients who had comorbid conditions such as allergic rhinitis, dyspepsia, disorders of menstruation, and disease of the musculoskeletal system and connective tissue tended to visit TCM clinics. CONCLUSIONS: Adjunctive TCM use is not low in Taiwanese children with cancer. Further studies to investigate the efficacy and safety of TCM in children with cancer are warranted. PMID- 27405935 TI - Social Participation and Mortality Among Older Adults in Singapore: Does Ethnicity Explain Gender Differences? AB - Objectives: Social participation has been consistently associated with lower risk of all-cause mortality, but studies have been ambivalent about how this association differs between men and women. The present study investigates if ethnicity accounts for gender differences in (a) the types of social activities older adults participate in and (b) the association between social participation and 4-year mortality. Methods: Data from 4,482 Singaporean older adults who participated in a nationally representative longitudinal survey were analyzed. Stepwise logistic regressions and Cox proportional hazard models with inverse probability of treatment weights were used. Results: Men were more likely to engage in social activities compared with women, but this gender difference varied by ethnicity for three activities. Whereas going out to eat was associated with a lower risk of mortality for men only, playing sports was found to be protective for women only, but these associations did not vary by ethnicity. Discussion: Findings suggest that although ethnicity may account for gender differences in the content of social activity participation, it does not explain gender differences in the association between social participation and mortality. More consideration should be given to whether each activity provides an appropriate milieu for the social interaction of each gender. PMID- 27405934 TI - Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes. AB - The human skin barrier has an important role in protection and defense, reflected not only in the ability to resist entry of harmful substances into the human body, but also in the ability to prevent loss of water and nutrients. Once the skin barrier is damaged, the skin may become dry, scaly, and wrinkled, and a series of skin problems may occur. In this article, we review the composition of lipids, such as ceramides, cholesterol, and free fatty acids, in the skin and examine the expression of enzymes related to lipid metabolism, such as kallikreins, elongase of elongation of very long-chain fatty acids, hydrolases, and lipid synthases. Additionally, we discuss the involvement of these proteins in skin barrier function and structure. The information presented in this review is expected to provide a theoretical basis for the development of skin care products facilitating the maintenance and repair of skin barrier function. PMID- 27405936 TI - Stakeholder Views of Nanosilver Linings: Macroethics Education and Automated Text Analysis Through Participatory Governance Role Play in a Workshop Format. AB - The Nanosilver Linings role play case offers participants first-person experience with interpersonal interaction in the context of the wicked problems of emerging technology macroethics. In the fictional scenario, diverse societal stakeholders convene at a town hall meeting to consider whether a nanotechnology-enabled food packaging industry should be offered incentives to establish an operation in their economically struggling Midwestern city. This original creative work was built with a combination of elements, selected for their established pedagogical efficacy (e.g. active learning, case-based learning) and as topical dimensions of the realistic scenario (e.g. nanosilver in food packaging, occupational safety and health). The product life cycle is used as a framework for integrated consideration of scientific, societal, and ethical issues. The Nanosilver Linings hypothetical case was delivered through the format of the 3-hour workshop Ethics when Biocomplexity meets Human Complexity, providing an immersive, holistic ethics learning experience for STEM graduate students. Through their participation in the Nanosilver Linings case and Ethics when Biocomplexity meets Human Complexity workshop, four cohorts of science and engineering doctoral students reported the achievement of specific learning objectives pertaining to a range of macroethics concepts and professional practices, including stakeholder perspectives, communication, human values, and ethical frameworks. Automated text analysis of workshop transcripts revealed differences in sentiment and in ethical framework (consequentialism/deontology) preference between societal stakeholder roles. These resources have been recognized as ethics education exemplars by the U.S. National Academy of Engineering . PMID- 27405937 TI - Burst Out of the Dead Land by the Help of Spirituality: A Case Study of Living with Blindness and Cancer. AB - Blindness is one of the most complex problems related to health throughout the world. The condition is worse when such stress is accompanied with cancer. The aim of this case study was to introduce a patient with both these conditions who could come over her problems well. A phenomenological hermeneutic approach influenced by Ricoeur was used to explore the experience of the patient. Data were collected through unstructured and deep interview and by checking patient medical records. The patient is an Iranian 58-year-old teacher residing in Kerman who became blind at age 32 due to bloodshed inside the eye and was affected by breast cancer at age 52. The patient could come over these divine tests through the help of spirituality so that she believed blindness and cancer was the best events in her life. Spirituality is one of the human aspects that give meaning and purposes to life. Health care providers are suggested to implement spiritual strategies such as instructional workshops for increasing spirituality in settings, such as oncologic wards for patients to pass stages of adaptation to such great stresses easily and rapidly. PMID- 27405938 TI - [Clinical course and differential diagnosis of thrombotic microangiopathy]. AB - BACKGROUND: Thrombotic microangiopathies are complex diseases, requiring early differential diagnosis and targeted intervention. OBJECTIVES: Presentation of clinical phenotype and diagnostic algorithm, discussion of underlying pathophysiology, clinical management and therapy. METHODS: Summary of current knowledge from literature and expert opinion. RESULTS: Our understanding of pathophysiology and therapeutic options have changed substantially in recent years. Early differential diagnosis and targeted therapy are of prognostic relevance. CONCLUSIONS: A better understanding of underlying pathophysiology, increased clinical awareness and novel therapeutic options allow for a better prognosis of patients with thrombotic microangiopathy. PMID- 27405940 TI - [Blood pressure monitoring - Status quo and future : A contribution to the personalized medicine]. AB - Sustainment of life demands that the heart create sufficient pressure to maintain enough flow to keep the body healthy and oxygenated. Blood pressures can be easily measured, while volume measurements required additional invasive procedures. In analogy to volumetrically determined ejection fraction, a pressure ejection fraction EF(P) may be calculated. When standardized to heart rate and body surface area, a new, effective performance metric may be defined. These metrics enable the long-term monitoring of the critically ill patient. When presented in a performance diagram, the metrics contain prognostic implications and enable a real-time evaluation of the efficacy of therapeutic measures. Until now, pressure-related prognostic statements were based on statistical averages, which by definition apply to groups. With this new analytical approach, we have the ability to provide patient-specific therapeutics in an area of medicine that requires individualized treatment. Here, we show preliminary results of applying a mathematical risk analysis to blood pressure metrics to assess therapeutic risk. PMID- 27405939 TI - [Rotational thromboelastometry for the diagnosis of coagulation disorders]. AB - BACKGROUND: Compared to conventional coagulation assays, as prothrombin time (PT) or activated partial thromboplastin time (aPTT), viscoelastic methods of coagulation analysis, including rotational thromboelastometry (ROTEM(r), Tem International GmbH, Munich, Germany), yield prognostic benefits. Results of ROTEM(r) in citrated whole blood could be generated within 10-12 min and allow for a qualitative and semiquantitative characterisation of clot kinetics. Based on ROTEM(r) results, the switch between empiric approaches of treating coagulopathy to a goal-directed approach could be accelerated. Introduction of ROTEM(r) reduces transfusion requirements and the need for single factor concentrates. Thus, ROTEM(r) reduces transfusion-related adverse events, and additionally implement therapeutic cost effectiveness. OBJECTIVES: This review provides a short introduction in the methodology of ROTEM(r), showing how the combination of assays with different commercially available ROTEM(r) reagents allows for rapid differential diagnosis of common coagulopathies in clinical practice. Furthermore, prognostic benefits and limitations of ROTEM(r) diagnostics are described. Finally, we discuss the potential fields of ROTEM(r) application in different surgical settings. CONCLUSION: ROTEM(r) appears to be a contemporary, applicable and effective method in diagnosing coagulopathy and for subsequent algorithm-based goal-directed therapy. PMID- 27405941 TI - STN DBS for Parkinson's disease: results from a series of ten consecutive patients implanted under general anaesthesia with intraoperative use of 3D fluoroscopy to control lead placement. AB - BACKGROUND: Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) is a recognised treatment for advanced Parkinson's disease (PD). We present our results of 10 consecutive patients implanted under general anaesthesia (GA) using intraoperative robotic three-dimensional (3D) fluoroscopy (Artis Zeego; Siemens, Erlangen, Germany). METHOD: Ten patients (nine men, one woman) with a mean age of 57.6 (range, 41-67) years underwent surgery between October 2013 and January 2015. The mean duration of PD was 9.2 [1-10] year. The procedure was performed under GA: placement of the stereotactic frame, implantation of the electrodes (Lead 3389; Medtronic, Minnesota, MN, USA) and 3D intraoperative fluoroscopic control (Artis Zeego) with image fusion with the preoperative MRI scans. All patients were evaluated preoperatively and 6 months postoperatively. RESULTS: The mean operative time was 240.1 (185-325) min. The mean Unified Parkinson's Disease Rating Scale (UPDRS) II OFF medication decreased from 23.9 preoperatively to 15.7 postoperatively. The mean OFF medication UPDRS III decreased from 41 to 11.6 and the UPDRS IV decreased from 10.6 to 7. The mean preoperative and postoperative L Dopa doses were 1,178.5 and 696.5 mg, respectively. Two complications were recorded: one episode of transient confusion (24 h) and one internal pulse generator (IPG) infection. CONCLUSIONS: With improvement in preoperative magnetic resonance imaging (MRI) and the ability to control the position of the leads intraoperatively using Artis Zeego, we now perform this procedure under GA. Our results are comparable to others reported. The significant decrease in the duration of surgery could be associated with a reduced rate of complications (infection, loss of patient collaboration). However, this observation needs to be confirmed. PMID- 27405942 TI - SOCIOECONOMIC AND DEMOGRAPHIC VARIATION IN NUTRITIONAL STATUS OF UNDER-FIVE BANGLADESHI CHILDREN AND TREND OVER THE TWELVE-YEAR PERIOD 1996-2007. AB - The nutritional status of under-five-year-old children is a sensitive indicator of a country's health status as well as economic condition. The objectives of this study were to analyse trends in the nutritional status in Bangladeshi children over the period 1996-2007 and to examine the associations between nutritional and socioeconomic status variables. Bangladesh Demographic Health Surveys (BDHS) were the source of data, and a total of 16,278 children were examined. The Z-scores of the children were analysed as continuous as well as categorical variables (stunted, underweight and wasted). The socioeconomic status variables used were region, urban-rural residence, education and occupation of the parents, house type and household possession score. A series of General Linear Model and Sequential Linear and Binary Logistic Regression analyses were done to assess the relationship between demographic and socioeconomic variables and nutritional status. The trends of Z-scores were analysed by survey, as well as by child birth cohort. Region, house type, educational level of parents and household possession score showed significant associations with all three Z scores of children after removing the effects of age, period of DHS and other explanatory variables in the model. No significant sex difference was observed between any of the Z-scores. There were improvements in mean WAZ and HAZ between 1996 and 2007 but deterioration in mean WHZ over this period. The obesity rate was below 2% in 2007, although the absolute numbers of obese children had nearly doubled in this 12-year period. Children from poorer households showed greater improvement than their better-off counterparts. The study reveals that over the years there has been substantial improvement in nutritional status of under-five children in Bangladesh and the main gains have been amongst the lower socioeconomic groups; it is also evident that malnutrition in Bangladesh is a multidimensional problem, like poverty itself, and warrants a proper policy mix and programme intervention. PMID- 27405943 TI - Low-density lipoprotein oxidation and atherogenesis: we got the bandwagon, we got the band, but where's the music? PMID- 27405945 TI - A pathologist's prognosis for 'redox reaction' profiles. PMID- 27405944 TI - Is your manuscript ready for Free Radical Redox Report of Research in Biology and Medicine? A guide for authors. PMID- 27405946 TI - Oxygen sensing and response to hypoxia by mammalian cells. AB - Cells are able to sense reduced oxygen tension and modulate the expression of specific genes in order to adapt to hypoxic conditions. In the carotid body and pulmonary neuroepithelial bodies a heme-containing nicotinamide-adenine dinucleotide phosphate oxidase-coupled potassium channel serves as an oxygen sensor. Membrane depolarization triggers an increase in intracellular calcium levels and cellular responses. Hemoproteins may also sense oxygen In non depolarizable cells. Hypoxia signal transduction involves protein phosphorylation and is affected by cellular redox state. Src, Ras, Raf and MAP kinases have been implicated in some systems involving hypoxia signal transduction. Gene products that are induced by hypoxia include cytokines, metabolic enzymes, transcription factors, cellular redox regulators and protective proteins. Study of hypoxic activation of erythropoietin gene transcription identified a hypoxia-inducible enhancer and transcription factor HIF-1 (hypoxia-inducible factor 1). Recent evidence suggests that HIF-1 may regulate transcription of hypoxia-inducible genes in a variety of cell types in cooperation with other transcription factors and may play an important role in coupling signal transduction pathways to the transcriptional activation of hypoxia inducible genes. PMID- 27405947 TI - Cell-mediated oxidation of low-density lipoprotein: the elusive mechanism(s). AB - Low-density lipoprotein (LDL) oxidation is believed to be causal in the process of atherosclerosis. Evidence suggests that this oxidation occurs in the arterial intima and is almost certainly mediated by the surrounding cells. Mechanisms by which cells could promote oxidation may be one or more of the following: 1. direct action of cell-derived oxidants (e.g. hydrogen peroxide, superoxide radical, hypochlorous acid, peroxynitrous acid); 2. transfer of cell-derived lipid hydroperoxides to LDL; 3. exposure of LDL to cell-derived oxidizing enzymes (e.g. lipoxygenase) which use LDL directly as a substrate; 4. maintenance of transition metals in a reduced and therefore highly reactive state (e.g. by thiols or other mechanisms); 5. generation of a local microenvironment (e.g. modulation of pH, pO2, antioxidants) which promotes metal-catalysed lipid peroxidation. In vitro cell-mediated LDL oxidation is absolutely metal-dependent and although the mechanism involved is not yet defined, evidence to date is most consistent with maintenance of metals in the reduced state as the predominant route. PMID- 27405948 TI - Stimulated chemiluminescence in several models of oxidative stress. AB - It had been suggested that increased chemiluminescence, stimulated by tertiary butylhydroperoxide (t-BuOOH) resulted from tissues which had undergone previous oxidative stress. Therefore, we tested animals subjected to various conditions generally regarded to cause oxidative stress, then removed relevant target organs and measured t-BuOOH stimulated (and unstimulated) chemiluminescence from biopsy sized samples of these tissues. The conditions chosen included 5000 rads whole body irradiation, hyperoxia, ischaemia-reperfusion and chronic indomethacin (a non-steroidal anti-inflammatory drug) treatment, with determination of chemiluminescence from samples of stomach and thymus after irradiation, brain and lungs after hyperoxia, kidney and stomach following ischaemia-reperfusion, and ileum and jejunum after chronic indomethacin administration. Neutrophils were also measured in the latter model. We cannot substantiate the claim that t-BuOOH stimulated chemiluminescence is a reliable indicator that a tissue has undergone oxidative stress. Large increases in stimulated chemiluminescence occurred only in frankly ulcerated tissue of the gastrointestinal tract and this enhanced chemiluminescence may be associated with increased neutrophils infiltrating the ulcer site. PMID- 27405949 TI - Superoxide is not the proximate cause of paraquat toxicity. AB - Paraquat toxicity is thought to occur through the production of superoxide O2(.-) and it has been argued that this oxygen radical species is, itself, an important mediator of the toxicity of this drug. If so, a direct relationship should exist between the steady-state amounts of O2(.-) produced and the lethal effects of paraquat. We have therefore examined O2(.-) mediated chemiluminescence and paraquat sensitivity in bacteria with widely varying superoxide dismutase (SOD) activities. As expected, bacteria with high SOD activity exhibit minimal (lucigenin enhanced) chemiluminescence in the presence of paraquat whereas SOD deficient bacteria show >90-fold higher chemiluminescence compared to parental strains. Nonetheless, high SOD bacteria are more readily killed by paraquat whereas SOD-deficient organisms show no increased susceptibility to this agent. This further supports our earlier conclusions that hypertrophied SOD activity is inadequate defense against paraquat and that O2(.-) is probably not the proximate toxin by which paraquat mediates cellular injury. PMID- 27405950 TI - Changes in rat plasma-free fatty acid composition under oxidative stress induced by carbon tetrachloride: decrease of polyunsaturated fatty acids and increase of palmitoleic acid. AB - In order to measure the changes in antioxidant levels and the composition of plasma-free fatty acids resulting from oxidative stress, male Fisher rats were given a twice weekly subcutaneous injection of a 50% solution of carbon tetrachloride (CCl4) in corn oil for a period of 2 to 13 weeks. The dosage was 1.3 ml/kg of body weight. This treatment significantly suppressed the gain of body weight compared with control rats receiving the same dosage of corn oil. Liver weight of the two groups was similar while necrosis and hyperplasia of hepatocytes and liver fibrosis were observed in CCl4 treated rats. Increased levels of plasma glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase were indicative that hepatocyte necrosis was induced by CCl4. Increased oxidative stress in CCl4 treated rats was indicated by a significant decrease of liver ascorbate and a decrease in the plasma ratio of polyunsaturated fatty acids (PUFA) to total free fatty acids. Interestingly, a significant increase of palmitoleic acid was observed in CCl4 treated rats, which may compensate for the loss of PUFA. The possibility of using the plasma composition of PUFA and palmitoleic acid as a marker of oxidative stress is discussed. PMID- 27405951 TI - Lack of effect of copper on advanced Maillard reaction and glucose autoxidation at physiological concentrations of albumin. AB - This study examines the possible action of copper on advanced glycation. Copper has been shown to induce fluorescence due to advanced-glycated-end-products (AGEs) on albumin incubated with glucose, and this was interpreted as activation of the glucose or Amadori product (AP) autoxidation. We glycated albumin (60 g/L) to several levels with increasing concentrations of glucose. The dialysed glucose free glycated albumin was then incubated with 1.5 MUmol/L copper or 1 mmol/L diethylenetriaminepentaacetic acid (DTPA), plus or minus glucose. The production of AP, measured as furosine, was similar whether DTPA or copper was present in the incubation medium. It linearly increased as a function of time and glucose concentration in both cases up to a maximum (furosine around 20 mmol/g protein), indicating saturation of the free NH2 residues on the protein. The fluorescence due to AGEs increased linearly over time for glycated albumin incubated without glucose, and exponentially when glucose was added to the incubation medium. This fluorescence was also unaffected by DTPA or copper for a glucose concentration below 125 mmol/L and initial furosine below 10 mmol/g. However copper caused a slight activation in samples with very high glucose (1.25 mol/L) and furosine (30 40 mmol/g) concentrations. We therefore find no effect of copper in this experiment, because the copper concentration is lower and the albumin higher than that used in previous studies. In these conditions, albumin chelates copper and inhibits its oxidative activity. The protein concentrations used in most in vitro studies showing a copper effect were below 10 g/L with copper often above 10 MUmol/L, so that copper may act oxidatively. As the lens and arterial wall have high protein concentrations, copper should have no action on protein glycation in vivo, unless altered protein structure impedes the inactivation of copper by chelation. PMID- 27405952 TI - Structural dependence of nitroxide spin labels and nitroxide spin adducts on their reducibility by ascorbate ion. AB - The reducibility of a series of nitroxides (aminoxyls) by ascorbate was tested by measuring the nitroxide decay rates with a stopped-flow electron paramagnetic resonance technique in aqueous phosphate buffer solution. The dependence of reactivity on the structures and pH of the medium was found for both cyclic nitroxides and nitroxide adducts of phenyl N-tert butyl nitrone (PBN). In cyclic nitroxides, the ring size is a dominant factor in determining reaction rates but substituents have additional effects on the rate depending on their electronegativity. For alkyl and hydroxyalkyl adducts of PBN, at fixed ascorbate concentration, half-lives increase with lengthening of the substituent, suggesting that a long chain in the substituent sterically protects the nitroxide group and thus prevents its reduction by ascorbate. PMID- 27405953 TI - Enhancement of peroxidase-induced lipid peroxidation by indole-3-acetic acid: effect of antioxidants. AB - Indole-3-acetic acid (IAA) enhanced the peroxidase-induced lipid peroxidation in phosphatidylcholine liposomes, as measured by loss of fluorescence of cis parinaric acid. alpha-Tocopherol or beta-carotene in the lipid phase or ascorbate or Trolox in the aqueous phase inhibited the loss of fluorescence induced by the peroxidase + IAA system, but glutathione had only a small inhibitory effect. The peroxyl radical formed by one-electron oxidation of IAA, followed by decarboxylation and reaction with oxygen, is suggested to act as the initiator of lipid peroxidation. The protection by ascorbate or Trolox is explained by the reactivity of these compounds with the IAA indolyl radical, as shown by pulse radiolysis experiments, whereas the weak effect of glutathione agrees with its low reactivity towards the IAA-derived peroxyl radical and its precursors. PMID- 27405954 TI - Antioxidant action of acteoside and its analogs on lipid peroxidation. AB - We have investigated antioxidant actions of acteoside (ACT) and another natural phenylpropanoid glycoside, cistanoside F (CIS-F) on lipid peroxidation in rat liver mitochondria (RLM) and rat liver mitochondrial lipid (RLML) liposomes induced by Fe(2+)/ADP. A synthetic ACT analogue, TX-1847, was also examined. Oxygen consumption, the formation of thiobarbituric acid reactive substances (TBARs) and glutathione concentration were determined simultaneously during lipid peroxidation. The radical scavenging activity of the compounds was evaluated by using 1,1-diphenyl-2-picrylhydrazyl. ACT and its analogs produced dose-dependent inhibitions of mitochondrial and liposomal lipid peroxidation (ACT ~ CIS-F > TX 1847). Their radical scavenging activities were ranked as follows: TX-1847 > ACT > CIS-F. ACT, CIS-F, and TX-1847 spared reduced glutathione (GSH) during mitochondrial lipid peroxidation. The radical scavenging activities of the compounds did not parallel their anti-peroxidative activities. The data are consistent with the idea that the inhibitory activities of phenylpropanoids were primarily due to a radical chain-breaking mechanism. The sugar moieties in ACT and CIS-F, and/or the conformational structure of the compounds, also seem to play an important role in their inhibitory effects on lipid peroxidation. PMID- 27405955 TI - Survivability of Deterministic Dynamical Systems. AB - The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures. PMID- 27405956 TI - Commonly used drugs and supplements can worsen heart failure, US doctors warn. PMID- 27405957 TI - Electronic properties of epitaxial cerium oxide films during controlled reduction and oxidation studied by resonant inelastic X-ray scattering. AB - We investigated the evolution of the electronic structure of cerium oxide ultrathin epitaxial films during reduction and oxidation processes using resonant inelastic X-ray scattering at the Ce L3 absorption edge, a technique sensitive to the electronic configurations at the 4f levels and in the 5d band thanks to its high energy resolution. We used thermal treatments in high vacuum and in oxygen partial pressure to induce a controlled and reversible degree of reduction in cerium oxide ultrathin epitaxial films of different thicknesses. Two dominant spectral components contribute to the measured spectra at the different degrees of oxidation/reduction. In ultrathin films a modification of the electronic properties associated with platinum substrate proximity and with dimensionality is identified. The different electronic properties induce a higher reducibility in ultrathin films, ascribed to a decrease of the surface oxygen vacancy formation energy. PMID- 27405958 TI - Endoscopic Detection of Small Bowel Dysplasia and Adenocarcinoma in Crohn's Disease: A Prospective Cohort-Study in High-Risk Patients. AB - BACKGROUND AND AIMS: Crohn's disease [CD] is associated with an increased risk of small bowel adenocarcinoma [SBA]. There are no recommendations on endoscopic screening of SBA in CD patients. The aim of this study was to evaluate the feasibility and value of endoscopic screening for SBA in CD patients at high-risk of SBA. METHODS: We performed an exploratory multi-centre study in a prospective cohort of CD patients at high-risk of SBA defined as long-term small bowel disease without bowel resection for the past 10 years. Depending on the location of the disease, baseline upper and/or lower enteroscopies were performed. Random and targeted biopsies using chromoendoscopy were taken. Patients were followed-up for at least 1 year after inclusion. RESULTS: In total, 101 patients [62 men; median age: 48 years; median duration of disease: 19 years] were recruited in ten centres. The endoscopic procedure was incomplete in 47 cases because of impassable strictures and dilation was performed in four patients. Indeterminate small bowel dysplasia was identified in two patients at endoscopic screening; SBA was confirmed in one after surgical resection. With an at least 1-year follow-up duration, two additional cases of SBA were identified in patients who underwent surgery for obstruction, resulting in a 33% sensitivity rate for SBA endoscopic screening. CONCLUSION: In a cohort of high-risk patients, the prevalence of dysplasia and SBA on CD was 4%. Because of its low sensitivity, endoscopic screening cannot be recommended for surveillance in CD patients at high-risk of SBA. PMID- 27405959 TI - Deciphering the function of the CNGB1b subunit in olfactory CNG channels. AB - Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore. In addition, we show that the CNGB1b subunit is the most sensitive subunit in a heterotetrameric channel to cyclic nucleotides and that it accelerates deactivation to a similar extent as does the CNGA4 subunit. In conclusion, the CNGB1b subunit participates in ligand-gated activation of olfactory CNG channels and, particularly, contributes to rapid termination of odorant signal in an olfactory sensory neuron. PMID- 27405962 TI - Bowen disease of the nail unit: a retrospective study of 12 cases and their association with human papillomaviruses. AB - BACKGROUND: Bowen disease is the most frequent nail malignancy, usually seen as a verrucous plaque of the nail in men. OBJECTIVE: To characterize the affected patient population, the clinical manifestations, the diagnostic delay and diagnostic steps, and presence of human papilloma virus (HPV) infection. METHODS: We retrospectively evaluated all cases of Bowen disease of the nail unit over a period of 9 years. Data were obtained from our electronic database. Human papilloma virus genotype was assessed in biopsy specimens by polymerase chain reaction (PCR) sequencing. RESULTS: We identified 12 cases of Bowen disease of the nail unit in 10 patients. Mean age at onset was 52 years, with a male predominance of 90%. The thumb and middle finger were the most frequently affected (66%). Fifty percent of the lesions presented as periungual and subungual verrucous tumours. Patients sought medical evaluation after a mean delay of 5.7 years; histopathological diagnosis was made after a mean delay of 3.2 years. HPV infection was identified in 75% of the cases. CONCLUSIONS: Any recently appeared verrucous lesion of the nail unit in men above the age of 40 years should raise the suspicion of Bowen disease and lead to further histopathological diagnostic procedures. PMID- 27405961 TI - Benzothiazinethione is a potent preclinical candidate for the treatment of drug resistant tuberculosis. AB - New chemotherapeutic compounds are needed to combat multidrug-resistant Mycobacterium tuberculosis (Mtb), which remains a serious public-health challenge. Decaprenylphosphoryl-beta-D-ribose 2'-epimerase (DprE1 enzyme) has been characterized as an attractive therapeutic target to address this urgent demand. Herein, we have identified a new class of DprE1 inhibitors benzothiazinethiones as antitubercular agents. Benzothiazinethione analogue SKLB TB1001 exhibited excellent activity against Mtb in the Microplate Alamar blue assay and intracellular model, meanwhile SKLB-TB1001 was also highly potent against multi-drug resistant extensively and drug resistant clinical isolates. Importantly, no antagonism interaction was found with any two-drug combinations tested in the present study and the combination of SKLB-TB1001 with rifampicin (RMP) was proved to be synergistic. Furthermore, benzothiazinethione showed superb in vivo antitubercular efficacy in an acute Mtb infection mouse model, significantly better than that of BTZ043. These data combined with the bioavailability and safety profiles of benzothiazinethione indicates SKLB-TB1001 is a promising preclinical candidate for the treatment of drug-resistant tuberculosis. PMID- 27405963 TI - Reduced Subendocardial Viability Ratio Is Associated With Unfavorable Cardiovascular Risk Profile in Women With Short Duration of Type 2 Diabetes. AB - BACKGROUND: The pathophysiological perturbations underlying the unfavorable cardiovascular prognosis in women with type 2 diabetes (T2DM) remain elusive. Low subendocardial viability ratio (SEVR), an index of myocardial oxygen supply and demand, has been associated with intermediate cardiovascular risk markers and cardiovascular mortality in various populations. However, whether SEVR is associated with sex and cardiovascular risk markers in patients with T2DM remains to be clarified. METHODS: We examined 86 T2DM patients (mean age 59+/-10 years, 47% women, median diabetes duration 1.9 (range 0.2-5.0) years) and 86 sex- and age-matched control subjects in a cross-sectional study. SEVR was noninvasively assessed by tonometry and markers of cardiovascular risk by carotid-femoral pulse wave velocity (PWV), homeostasis model assessment of insulin resistance (HOMA2 IR), C-reactive protein, urinary albumin/creatinine ratio, and heart rate variability. RESULTS: Women with diabetes had significantly lower SEVR compared to both men with diabetes (161% +/- 26% vs. 178% +/- 32%, P < 0.01), women without diabetes (185% +/- 24%, P < 0.001), and men without diabetes (188% +/- 28%, P < 0.001). The differences remained significant after adjustment for age, systolic blood pressure, heart rate, diabetes, and smoking. SEVR was associated with PWV, HOMA2-IR, C-reactive protein, and reduced heart rate variability in patients and control subjects, but the associations became nonsignificant after adjustment for heart rate. CONCLUSIONS: SEVR is reduced in women with short duration of T2DM and associated with cardiovascular risk markers. The latter association seems to be at least partly mediated via heart rate. We hypothesize that reduced SEVR may contribute to the unfavorable cardiovascular prognosis in women with diabetes. PMID- 27405964 TI - Arterial Stiffness: Going a Step Beyond. AB - Interest in arterial stiffness has been fueled by the scientific and clinical implications of its "vicious cycle" relationship with aging and systolic blood pressure. In physical terms, stiffness is the slope of the relationship between an artery's distending pressure and its cross-sectional area or volume. Pulse wave velocity (PWV, in m/s), the most common arterial stiffness indicator, is usually measured by the foot-to-foot time and distance method and is proportional to [stiffness * area (or volume)]1/2 at a given pressure. Its intrinsic pressure dependency and other flaws in current PWV methods limit its utility. In contrast, the arterial stiffness-arterial pressure relationship is near-linear, with a slope beta, the exponent of the curvilinear arterial pressure-arterial volume relationship. The concept of arterial stiffening is related to beta and describes a more functionally relevant aspect of arterial behavior: the change in stiffness for a given change in pressure. Arterial stiffening can be estimated from the variability of within-individual BP measurements (24-h ambulatory, home BP, or BP measured at different arm heights) and can be expressed as the pulse stiffening ratio (PSR) = [systolic stiffness]/[diastolic stiffness] or the ambulatory arterial stiffness index (AASI or its symmetric form, sAASI). High arterial stiffness (PWV) and stiffening (beta, stiffness index, cardio-ankle vascular index, AASI, and PSR) are associated with increased cardiovascular disease risk, but it remains unclear whether these indicators are useful in improving medical care quality; the standard of care remains stringent BP control. PMID- 27405960 TI - Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment. AB - Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them. PMID- 27405967 TI - Are We Banging Our Heads Against the Wall? The Effect of Treatment Head Wear on the Outcomes of Extracorporeal Shockwave Lithotripsy. AB - INTRODUCTION AND OBJECTIVE: The manufacturer for the Storz Modulith SLX-F2 lithotripter recommends treatment head exchange after 1.65 million shocks. However, there is no documentation describing longevity of the treatment head with continued usage. The objective of this study is to determine whether there is a difference in stone fragmentation effectiveness with the treatment head at the beginning versus the end of its treatment life. METHODS: We conducted a retrospective chart review of 200 patients-50 consecutive patients treated immediately preceding, and following, two separate treatment head exchanges. Primary outcome measures were stone-free rate (no stone), total stone fragmentation (any decrease in size), and fragmentation rate <=4 mm (decrease in size with largest residual fragment <=4 mm), based on most recent follow-up imaging post shockwave. RESULTS: There were no baseline characteristic differences between the pre-exchange and postexchange groups with respect to first time lithotripsy for the stone (85% vs. 77%), stone location, preoperative stenting (3% vs. 4%), mean stone density (912 hounsfield units [HU] vs. 840 HU), mean stone size (9.0 mm vs. 8.1 mm), stone location, and mean number of shocks delivered (3105 vs. 3089). Mean time to follow-up was 2.7 weeks in both groups, with most follow-up imaging consisting of a kidney ureter bladder X-ray (87% pre exchange vs. 85% postexchange). Stone free (34% vs. 27%), total stone fragmentation (76% vs. 76%), fragmentation <=4 mm (48% vs. 42%), re-treatment rates (38% vs. 51%), and complication rates (6% vs. 7%), were not statistically different between the pre and postexchange groups, respectively. CONCLUSIONS: Exchanging the Storz Modulith F2 lithotripter head at the manufacturer recommended 1.65 million shocks does not affect the stone-free or fragmentation rate. If the manufacturer's recommendation for treatment head longevity is based on clinical outcomes, then there is likely room to extend this number without affecting treatment efficacy. PMID- 27405965 TI - Frontal and Temporal Structural Connectivity Is Associated with Social Communication Impairment Following Traumatic Brain Injury. AB - OBJECTIVES: Although it has been well documented that traumatic brain injury (TBI) can result in communication impairment, little work to date has examined the relationship between social communication skills and structural brain integrity in patients with TBI. The aim of the current study was to investigate the association between self- and other-perceived communication problems and white matter integrity in patients with mild to severe TBI. METHODS: Forty-four individuals (TBI=24) and people with whom they frequently communicate, as well as demographically matched normal healthy comparisons (NC) and their frequent communication partners, were administered, respectively, the La-Trobe Communication Questionnaire Self form (LCQ-SELF) and Other form (LCQ-OTHER). In addition, diffusion tensor imaging data were collected, and fractional anisotropy (FA) measures were extracted for each lobe in both hemispheres. RESULTS: Within the TBI group, but not within the NC group, participants who were perceived by their close others as having more communication problems had lower FA in the left frontal and temporal lobes (p<.01), but not in other brain regions. CONCLUSIONS: Frontotemporal white matter microstructural integrity is associated with social communication abilities in adults with TBI. This finding contributes to our understanding of the mechanisms leading to communication impairment following TBI and can inform the development of new neuromodulation therapies as well as diagnostic tools. (JINS, 2016, 22, 705-716). PMID- 27405969 TI - Increased protein intake and corresponding renal acid load under a concurrent alkalizing diet regime. PMID- 27405968 TI - Resistance exercise training and in vitro skeletal muscle oxidative capacity in older adults. AB - Whether resistance exercise training (RET) improves skeletal muscle substrate oxidative capacity and reduces mitochondrial production of reactive oxygen species in older adults remains unclear. To address this, 19 older males (>=60 years) were randomized to a RET (n = 11) or to a waitlist control group (n = 8) that remained sedentary for 12 weeks. RET was comprised of three upper body and four lower body movements on resistance machines. One set of 8-12 repetitions to failure of each movement was performed on three nonconsecutive days/week. Improvements in chest press and leg press strength were assessed using a three repetition maximum (3 RM). Body composition was assessed via dual energy X-ray absorptiometry. Muscle biopsies were obtained from the vastus lateralis muscle at baseline and at both 3 weeks and 12 weeks. Palmitate and pyruvate oxidation rates were measured from the (14)CO2 produced from [1-(14)C] palmitic acid and [U (14)C] pyruvate, respectively, during incubation of muscle homogenates. PGC 1alpha, TFAM, and PPARdelta levels were quantified using qRT-PCR Citrate synthase (CS) and beta-HAD activities were determined spectrophotometrically. Mitochondrial production of reactive oxygen species (ROS) were assessed using the Amplex Red Hydrogen Peroxide/Peroxidase assay. There were no significant changes in body weight or body composition following the intervention. Chest press and leg press strength (3RM) increased ~34% (both P < 0.01) with RET There were no significant changes in pyruvate or fatty acid oxidation or in the expression of target genes with the intervention. There was a modest increase (P < 0.05) in betaHAD activity with RET at 12 weeks but the change in CS enzyme activity was not significant. In addition, there were no significant changes in ROS production in either group following RET Taken together, the findings of this study suggest that 12 weeks of low volume RET does not increase skeletal muscle oxidative capacity or reduce ROS production in older adults. PMID- 27405970 TI - Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men. AB - Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P < 0.01), indices of BA stiffness did not change (P >= 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P <= 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P <= 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P >= 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb. PMID- 27405971 TI - Remote ischemic perconditioning attenuates ischemia/reperfusion-induced downregulation of AQP2 in rat kidney. AB - Renal ischemia/reperfusion (I/R) can lead to impaired urine concentration ability and increased fractional excretion of sodium (FeNa). Local ischemic preconditioning improves renal water and sodium handling after I/R injury. Here, we investigate whether remote ischemic perconditioning (rIPeC) prevents dysregulation of renal water and salt handling in response to I/R injury and mechanisms that may be involved. Rats were subjected to right nephrectomy and randomized into a sham group or an I/R group. In the I/R group, rats were subjected to 37 min of renal ischemia and 3 days of reperfusion. rIPeC was applied to the abdominal aorta. Blood and urine were collected on day 3 postoperatively for clearance studies. The expression of aquaporins (AQPs) and the sodium transporter Na-K-ATPase were analyzed using immunoblotting and immunohistochemistry. I/R injury resulted in polyuria, increased FeNa, and decreased urine osmolality compared to sham rats. rIPeC attenuated the increase in FeNa and the decrease in urine osmolality. Expression of AQP1, AQP2, phosphorylated AQP2 (pAQP2), and Na-K-ATPase was downregulated in I/R rats. rIPeC attenuated the reductions in AQP2 and pAQP2 expression. Immunohistochemistry revealed decreased labeling of Na-K-ATPase in the outer medulla in I/R kidneys compared to kidneys from sham and I/R + rIPeC rats. After renal ischemia, the expression of Na-K-ATPase was substantially reduced in the outer medullary thick ascending limb. In conclusion, our data suggest that rIPeC might prevent dysregulation of renal water and salt handling via regulation of AQP2 expression and phosphorylation as well as via regulation of Na-K-ATPase expression in I/R rat kidneys. PMID- 27405973 TI - Assembling substrate-less plasmonic metacrystals at the oil/water interface for multiplex ultratrace analyte detection. AB - Current substrate-less SERS platforms are limited to uncontrolled aggregation of plasmonic nanoparticles or quasi-crystalline arrays of spherical nanoparticles, with no study on how the lattice structures formed by nanoparticle self-assembly affect their detection capabilities. Here, we organize Ag octahedral building blocks into two large-area plasmonic metacrystals at the oil/water interface, and investigate their in situ SERS sensing capabilities. Amphiphilic octahedra assemble into a hexagonal close-packed metacrystal, while hydrophobic octahedra assemble into an open square metacrystal. The lower packing density square metacrystal gives rise to much stronger SERS enhancement than the denser packing hexagonal metacrystal, arising from the larger areas of plasmonic hotspots within the square metacrystal at the excitation wavelength. We further demonstrate the ability of the square metacrystal to achieve quantitative ultratrace detection of analytes from both the aqueous and organic phases. Detection limits are at the nano-molar levels, with analytical enhancement factors reaching 10(8). In addition, multiplex detection across both phases can be achieved in situ without any loss of signal quantitation. PMID- 27405972 TI - Effectiveness of ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroids: a multicentre study in China. AB - PURPOSE: To evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (PMWA) therapy for symptomatic uterine fibroids in a multicentre study. MATERIALS AND METHODS: Patients with symptomatic uterine fibroids who underwent PMWA at multiple treatment centres in China between January 2013 and August 2015 were prospectively studied to compare the reduction rate of uterine fibroids, haemoglobin level and uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL) scores before and at 3, 6 and 12 months after ablation. RESULTS: A total of 311 patients (405 leiomyomas) from eight treatment centres underwent the treatment (age, 29-55 years; mean +/- SD, 41 +/- 5.11 years). The mean diameter of the myomas ranged from 2.03 to 12.50 cm (mean, 5.10 +/- 1.28 cm) and the volume ranged from 4.40 to 1022.14 cm3 (mean, 95.01 +/- 70.29 cm3). Forty-eight myomas were identified as FIGO type 1/2 fibroids, 256 as type 3/4 fibroids and 101 as type 5/6 fibroids. The mean ablation rate was 86.6% (54.0-100%). The mean reduction rate was 63.5%, 78.5% and 86.7% at 3, 6 and 12 months posttreatment, respectively. The haemoglobin level increased significantly from 88.84 +/- 9.31 g/L before treatment to 107.14 +/- 13.32, 116.05 +/- 7.66 and 117.79 +/- 6.51 g/L at 3, 6 and 12 months posttreatment, respectively (p = .000). The symptom severity score (SSS) and health-related quality of life (HRQL) scores were also significantly improved posttreatment compared with before treatment (p = .000). CONCLUSION: PMWA is an effective, minimally invasive treatment for symptomatic leiomyomas that can significantly improve the quality of life of patients. PMID- 27405974 TI - Has the biobank bubble burst? Withstanding the challenges for sustainable biobanking in the digital era. AB - Biobanks have been heralded as essential tools for translating biomedical research into practice, driving precision medicine to improve pathways for global healthcare treatment and services. Many nations have established specific governance systems to facilitate research and to address the complex ethical, legal and social challenges that they present, but this has not lead to uniformity across the world. Despite significant progress in responding to the ethical, legal and social implications of biobanking, operational, sustainability and funding challenges continue to emerge. No coherent strategy has yet been identified for addressing them. This has brought into question the overall viability and usefulness of biobanks in light of the significant resources required to keep them running. This review sets out the challenges that the biobanking community has had to overcome since their inception in the early 2000s. The first section provides a brief outline of the diversity in biobank and regulatory architecture in seven countries: Australia, Germany, Japan, Singapore, Taiwan, the UK, and the USA. The article then discusses four waves of responses to biobanking challenges. This article had its genesis in a discussion on biobanks during the Centre for Health, Law and Emerging Technologies (HeLEX) conference in Oxford UK, co-sponsored by the Centre for Law and Genetics (University of Tasmania). This article aims to provide a review of the issues associated with biobank practices and governance, with a view to informing the future course of both large-scale and smaller scale biobanks. PMID- 27405975 TI - Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats. AB - PURPOSE: We aimed to evaluate the effect of IL-10 gene transfection on endothelial progenitor cells (EPCs) under inflammatory conditions, and explore the therapeutic potential of IL-10-transfected EPC transplantation on nonproliferative diabetic retinopathy (NPDR). METHODS: Lentivirus vectors encoding IL-10 were constructed and introduced into EPCs isolated from rat bone marrow. After exposure to recombinant rat TNF-alpha, abilities of nontransfected EPCs (non-EPCs) and EPCs transfected with normal control lentivirus (EPCs-GFP) or IL-10 expressing lentivirus (EPCs-IL-10-GFP) were assessed, including migration, adhesion, and tube formation. IL-10 production by EPCs-IL-10-GFP was determined by ELISA. Following 12 weeks after establishment of diabetes, diabetic rats were randomly injected with non-EPCs, EPCs-GFP, or EPCs-IL-10-GFP via tail vein. Expression of inflammatory factors and factors associated with nuclear factor kappa B (NF-kB) signal pathway, retinal histological analysis, and retinal vascular permeability were assessed 2 weeks after transplantation. RESULTS: The detrimental effects of TNF-alpha on the abilities of EPCs were significantly attenuated in EPCs-IL-10-GFP compared with non-EPCs and EPCs-GFP. The concentration of IL-10 in the EPCs-IL-10-GFP group was significantly higher than the non-EPCs and EPCs-GFP groups. Additionally, transplantation of EPCs-IL-10-GFP significantly inhibited inflammatory factors expression and activation of NF-kB signal pathway, improved retinal histological changes, and attenuated retinal vascular permeability. CONCLUSION: In conclusion, transplantation of IL-10 transfected EPCs significantly improved EPCs-mediated retinal vascular repair and subsequently suppressed NPDR progression. This was associated with inflammation suppression, at least partly via inhibiting the NF-kB signal pathway. Transplantation of IL-10-transfected EPCs may be a new strategy for treatment of NPDR. PMID- 27405977 TI - Signaling proteins in the spotlight. AB - The molecular side of signaling still has many secrets to reveal. This Editorial Guide describes areas of particular interest with regard to understanding cellular regulation at the level of individual molecules and macromolecular complexes. Advances in technology and the accumulation of proteomic and genomic data reveal previously unknown components of signaling networks, the spatial organization of macromolecular complexes, and how information flows through the networks to produce specific cellular responses. PMID- 27405976 TI - Variability of panretinal photocoagulation lesions across physicians and patients. Quantification of diameter and intensity variation. AB - BACKGROUND: Photocoagulation lesion intensity relies on the judgement of retinal blanching. Lesions turn out variable due to observer-dependent judgement and time dependency of blanching. We investigated lesion variability per patient and per physician in clinical routine treatments. METHODS: In this observational clinical trial, different physicians performed panretinal photocoagulation for diabetic retinopathy. Study eyes received 20-30 study lesions at 20 ms (three physicians, nine eyes) and 200 ms (four physicians, 12 eyes) irradiation time (532 nm continuous wave photocoagulator, 300 MUm spot size). Lesions were imaged after 1 hour with photography and optical coherence tomography (OCT). We measured lesion diameters in fundus and OCT images, and graded intensities according to a previously published six-step classifier. RESULTS: 200-ms lesions were larger and more severe (568, 474-625 MUm [median, IQR], predominantly class 6) than 20-ms lesions (397, 347-459 MUm, predominantly classes 3-4). The impact of laser power was small compared to other factors. Lesion intensities and diameters in fundus and OCT images varied significantly between patients and between physicians. Median photographic lesion diameters varied by up to a factor of 1.61 (20 ms) or 1.5 (200 ms) respectively. CONCLUSIONS: In this study, the treated area of retina varied by up to a factor of 1.612 = 2.59 for a given spot number. As clinical efficacy depends on the treated area, which is a function of lesion number by area per lesion, our results implicate poor control of the overall treatment effect if treatments are administered according to lesion number or spacing alone. Better ways of laser effect control should be sought. PMID- 27405978 TI - Science Signaling Podcast for 12 July 2016: Adaptor proteins limit signaling. AB - This Podcast features an interview with Steven Wiley, senior author of a Research Article that appears in the 12 July 2016 issue of Science Signaling, about how the abundance of adaptor proteins and feedback regulators affect the flow of information downstream of the epidermal growth factor receptor (EGFR). Information flows through a signaling pathway by sequential interactions between core components of the pathway, many of which have enzymatic activity. Adaptor proteins do not directly participate in relaying the signal and do not have enzymatic activity, but are important for signaling because they facilitate interactions between the core components. Using quantitative methods, Shi et al demonstrated that core components of the EGFR pathway were highly abundant in both normal cells and cancer cells. However, adaptor proteins were present in much lower abundance in both cell types, indicating that it is the abundance of these proteins that limit signaling downstream of EGFR. The authors also found that differences in EGFR signaling between different cell types likely resulted from the variable abundance of feedback regulators.Listen to Podcast. PMID- 27405979 TI - Bimolecular complementation affinity purification (BiCAP) reveals dimer-specific protein interactions for ERBB2 dimers. AB - The dynamic assembly of multiprotein complexes is a central mechanism of many cell signaling pathways. This process is key to maintaining the spatiotemporal specificity required for an accurate, yet adaptive, response to rapidly changing cellular conditions. We describe a technique for the specific isolation and downstream proteomic characterization of any two interacting proteins, to the exclusion of their individual moieties and competing binding partners. We termed the approach bimolecular complementation affinity purification (BiCAP) because it combines the use of conformation-specific nanobodies with a protein-fragment complementation assay with affinity purification. Using BiCAP, we characterized the specific interactome of the epidermal growth factor receptor (EGFR) family member ERBB2 when in the form of a homodimer or when in the form of a heterodimer with either EGFR or ERBB3. We identified dimer-specific interaction patterns for key adaptor proteins and identified a number of previously unknown interacting partners. Functional analysis for one of these newly identified partners revealed a noncanonical mechanism of extracellular signal-regulated kinase (ERK) activation that is specific to the ERBB2:ERBB3 heterodimer and acts through the adaptor protein FAM59A in breast cancer cells. PMID- 27405980 TI - Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways. AB - Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime macrophages for the subsequent activation of TLR7, which leads to synergistically increased production of cytokines. By developing a calibrated mathematical model for the kinetics of TLR3 and TLR7 pathway crosstalk and providing experimental validation, we demonstrated the involvement of the Janus activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in controlling the synergistic production of cytokines. Signaling through this pathway played a dual role: It mediated the synergistic production of cytokines, thus boosting the immune response, and it also maintained homeostasis to avoid an excessive inflammatory response. Thus, we propose that the JAK-STAT pathway provides a cytokine rheostat mechanism, which enables macrophages to fine tune their responses to multiple, temporally separated infection events involving the TLR3 and TLR7 pathways. PMID- 27405981 TI - Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway. AB - Various genetic mutations associated with cancer are known to alter cell signaling, but it is not clear whether they dysregulate signaling pathways by altering the abundance of pathway proteins. Using a combination of RNA sequencing and ultrasensitive targeted proteomics, we defined the primary components-16 core proteins and 10 feedback regulators-of the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway in normal human mammary epithelial cells and then quantified their absolute abundance across a panel of normal and breast cancer cell lines as well as fibroblasts. We found that core pathway proteins were present at very similar concentrations across all cell types, with a variance similar to that of proteins previously shown to display conserved abundances across species. In contrast, EGFR and transcriptionally controlled feedback regulators were present at highly variable concentrations. The absolute abundance of most core proteins was between 50,000 and 70,000 copies per cell, but the adaptors SOS1, SOS2, and GAB1 were found at far lower amounts (2000 to 5000 copies per cell). MAPK signaling showed saturation in all cells between 3000 and 10,000 occupied EGFRs, consistent with the idea that adaptors limit signaling. Our results suggest that the relative stoichiometry of core MAPK pathway proteins is very similar across different cell types, with cell-specific differences mostly restricted to variable amounts of feedback regulators and receptors. The low abundance of adaptors relative to EGFR could be responsible for previous observations that only a fraction of total cell surface EGFR is capable of rapid endocytosis, high-affinity binding, and mitogenic signaling. PMID- 27405982 TI - The role of nuclear factor of activated T cells during phorbol myristate acetate induced cardiac differentiation of mesenchymal stem cells. AB - BACKGROUND: We previously reported that phorbol 12-myristate 13-acetate (PMA) treatment can induce the cardiac differentiation of mesenchymal stem cells (MSCs). In the present study, we investigated how PMA induces cardiac differentiation of MSCs, focusing on its effect on the transcription factors responsible for increased cardiac marker gene expression. METHODS: Human MSCs (hMSCs) were treated with 1 MUM PMA for 9 days. The expression of MSC markers and cardiac markers in the PMA-treated hMSC, as well as the nuclear translocation of transcription factors, nuclear factor of activated T cells (NFAT), and myogenic differentiation 1 (MyoD), was examined. Transcriptional activity of NFAT was examined by utilizing a green fluorescent protein (GFP) vector containing NFAT motif of human interleukin-2 promoter. The effect of PMA on the expression of key cell cycle regulators was examined. RESULTS: PMA induces the transcriptional activity of NFAT and MyoD, which have been associated with increased expression of cardiac troponin T (cTnT) and myosin heavy chain (MHC), respectively. Our data suggested that protein kinase C (PKC) mediates the effect of PMA on NFAT activation. Furthermore, PMA treatment increased cell-cycle regulator p27(kip1) expression, suggesting that PMA triggers the cardiac differentiation program in MSCs by regulating key transcription factors and cell cycle regulators. CONCLUSIONS: The results of this study demonstrate the importance of NFAT activation during PMA-induced MSC differentiation and help us to better understand the underlying mechanisms of small molecule-mediated MSC differentiation so that we can develop a strategy for synthesizing novel and improved differentiation-inducing small molecules. PMID- 27405983 TI - The Results of ACES (Antihypertensive Combinations' Long Term Efficacy Comparing Study): Analysis of Metabolic Effects of Antihypertensive Combination Therapies. AB - BACKGROUND: More than 50 % of hypertensive patients have lipid disorders, and one third of hypertensive patients have impaired glucose metabolism. Owing to the high prevalence of metabolic risk factors and/or comorbidities, antihypertensives with favorable or neutral metabolic effects are preferred. Based on the available evidence, diuretics and beta-blockers are heterogeneous regarding their metabolic effects. OBJECTIVE: The aim of ACES (Antihypertensive Combinations' Long Term Efficacy Comparing Study) was to compare the efficacy and metabolic effects of a carvedilol/indapamide free combination, a fixed-dose combination of perindopril/amlodipine, and a fixed combination of perindopril/indapamide in everyday practice. METHODS: This study was a 6-month, multi-center, prospective, observational, non-interventional, open-label clinical study. The data of 9124 outpatients (4898 female, 4226 male; mean age 61.7 +/- 11.7 years) with mild, moderate, or severe essential (primary) hypertension with one or more metabolic risk factors were subjected to statistical analysis. At visits one (day 1), three (month 3), and four (month 6), the following metabolic parameters were monitored: fasting blood glucose, glycosylated hemoglobin, estimated glomerular filtration rate, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and serum potassium, sodium, creatinine, and uric acid levels. A total of 3888 patients took perindopril/amlodipine, while 2992 took perindopril/indapamide, and 2244 took a combination of carvedilol/indapamide. Statistical analysis was carried out using the one-paired t test and the Chi square test; the two-sided level of significance was set at 0.05. RESULTS: The observed changes in the main metabolic parameters were favorable and similar in all therapeutic groups: fasting blood glucose decreased by 5.5-5.5-5.5 %, total cholesterol by 9.0-10.2-9.9 %, and triglycerides by 12.7 15.4-13.8 % (respectively in perindopril/amlodipine, perindopril/indapamide and carvedilol/indapamide groups). CONCLUSIONS: Based on our findings, we conclude that the metabolic profile of indapamide is very similar to the metabolically neutral and well-documented metabolic profiles of the calcium-channel blocker amlodipine and the vasodilator beta-blocker carvedilol and that all the combinations studied had similar beneficial effects on the main metabolic parameters. The favorable changes of metabolic parameters are because of the discontinuation of active substances (e.g., conventional thiazides, second generation beta-blockers) used in the previous therapy, which were associated with unfavorable metabolic effects, and to the increase in the ratio of administered lipid-lowering drugs and oral antidiabetic drugs. PMID- 27405984 TI - Potential Effectiveness of Tolvaptan to Improve Ascites Unresponsive to Standard Diuretics and Overall Survival in Patients with Decompensated Liver Cirrhosis. AB - BACKGROUND AND OBJECTIVE: After tolvaptan was approved for the treatment of cirrhosis patients with ascites, only a few studies have reported its efficacy in the real clinical setting, and no studies have reported its contribution to overall survival. This study clarified the clinical outcomes of tolvaptan treatment in terms of improving ascites unresponsive to standard diuretics (AUS) and overall survival. METHODS: We retrospectively enrolled 80 decompensated cirrhosis patients with AUS who were administered tolvaptan from October 2012 to December 2014. The patients were divided into two groups according to ascites improvement. We compared laboratory results and overall survival and analyzed factors that affected overall survival. RESULTS: Of the 80 patients, 59 (73.8 %) were male and the median age was 70 years. Thirty-nine (48.8 %) patients were Child-Pugh class C, and 36 (45.0 %) had advanced hepatocellular carcinoma (HCC). Tolvaptan was effective in 48 (60.0 %) patients with an average 3.8 kg weight reduction and ineffective in 32 (40.0 %) patients. The cumulative survival rate differed significantly between the two groups (p < 0.0001), with 87.5 and 68.0 % survival at 30 and 90 days, respectively, in the effective group, and 50.0 and 30.5 % survival, respectively, in the ineffective group. Multivariate analysis showed that improvement in AUS, advanced HCC, total bilirubin level, blood urea nitrogen level, and the presence of hyponatremia were independent predictors of overall survival. CONCLUSIONS: Tolvaptan could possibly improve overall survival in decompensated cirrhosis patients with AUS as long as it was demonstrated to be effective in these patients. PMID- 27405986 TI - 2016 Colorado alphaherpesvirus latency society symposium. PMID- 27405985 TI - A critical view on cardiovascular risk in systemic sclerosis. AB - Systemic Sclerosis (SSc) is an autoimmune disorder characterized by microvascular injury and diffuse fibrosis of the skin and internal organs. While macrovascular disease and higher risk for cardiovascular events are well documented in other systemic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, the presence and extent of atherosclerosis among patients with SSc is yet to be established. Primary cardiac involvement, due to impairment of coronary microvascular circulation and myocardial fibrosis, considerably affects prognosis and life expectancy of individuals with SSc, representing one of the leading causes of death in this population. On the other hand the existence and prevalence of atherosclerotic coronary disease remains an issue of debate as studies comparing structural and morphological markers of atherosclerosis and cardiovascular events between SSc patients and the general population have yielded controversial results. The aim of this review is to summarize recent literature about the prevalence of cardiovascular disease in SSc, review the surrogate markers of CVD that have been evaluated and examine whether common pathogenic mechanisms exist between SSc and macrovascular disease. PMID- 27405987 TI - Normonatremic osmotic demyelination in the setting of acquired immune deficiency syndrome and malnutrition: case report and literature review. AB - In this report, we present the case of a 43-year-old woman with AIDS, disseminated aspergillosis, and malnutrition who developed osmotic demyelination syndrome. AIDS-related osmotic demyelination has only been documented in a handful of cases to date, and it appears independent of the classic mechanism of rapid correction of hyponatremia. In this manuscript, we review the six prior cases of osmotic demyelination in AIDS patients and compare their circumstances to that of our own patient. It appears that complications of malnutrition, possibly related to depletion of organic osmolytes in the central nervous system, may place AIDS patients at greater risk of osmotic demyelination. These, and other proposed mechanisms, deserve further inquiry. PMID- 27405988 TI - Grass carp reovirus NS26 interacts with cellular lipopolysaccharide-induced tumor necrosis factor-alpha factor, LITAF. AB - The nonstructural protein NS26 of grass carp reovirus (GCRV) is encoded by the 11th genomic dsRNA segment, homolog of which is not found in orthoreoviruses. The role of NS26 in GCRV pathogenesis is still unclear. Previously, grass carp LITAF/SIMPLE protein was identified as a putative binding partner for NS26 in a yeast two-hybrid screen. Here, we further characterized the association between NS26 and LITAF using in vivo and in vitro protein interaction assays. Soluble GST NS26 and His6-LITAF were expressed and purified from E. coli; recombinant NS26 tagged with myc and LITAF tagged with GFP were expressed in Ctenopharyngon idellus kidney cells (CIK) by transient transfection experiments. A GST pulldown assay demonstrated that GST-tagged NS26 efficiently bound to His6-LITAF. Co immunoprecipitation assays demonstrated that GCRV NS26 reciprocally precipitated endogenous LITAF in CIK cells. Double-immunofluorescent analyses revealed myc NS26 colocalized with GFP-LITAF in CIK cells. Taken together, the current in vitro and in vivo data demonstrated the interaction between cellular LITAF and GCRV NS26. PMID- 27405989 TI - A Longitudinal Study of Adenoma Detection Rate in Gastroenterology Fellowship Training. AB - BACKGROUND: Current guidelines suggest that a gastroenterology fellow in training needs to perform 140 colonoscopies to achieve competency. Data are limited regarding adenoma detection rate (ADR) in fellowship. AIMS: To assess how fellow ADR correlates with number of colonoscopies performed. METHODS: We performed a retrospective study examining consecutive colonoscopies performed by gastroenterology fellows. Fellow ADR before and after the 140 procedure benchmark was compared to colonoscopies performed by attending only with whom these fellows trained. A threshold for ideal procedure count was performed using ROC analysis. RESULTS: We analyzed 2021 average-risk colonoscopies performed by 10 gastroenterology fellows under the supervision of an attending physician. When fellows had performed <140 colonoscopies, the ADR was 27 % compared with an ADR of 36 % when fellows had performed >140 colonoscopies under attending supervision (p = 0.02). The ADR of fellows who had performed >140 colonoscopies under attending supervision was greater than that of attending-only colonoscopies (36 vs. 25 %, p < 0.0001). A threshold of >325 (male patients) and 539 (female patients) colonoscopies was determined to be ideal for achieving adequate ADR based on ROC analysis. CONCLUSIONS: Our data suggest that ADR increases after fellows perform >140 colonoscopies under attending supervision, and thereafter surpasses the ADR of attending-only colonoscopies. Some of the differences may be driven by detection of small adenomas. The findings of this study suggest that a higher threshold for number of colonoscopies performed under attending supervision may be needed to achieve adequate ADR during fellowship prior to independent practice. PMID- 27405990 TI - Recalibrating the Child-Turcotte-Pugh Score to Improve Prediction of Transplant Free Survival in Patients with Cirrhosis. AB - BACKGROUND: The Child-Turcotte-Pugh (CTP) score is a widely used and validated predictor of long-term survival in cirrhosis. However, the cutpoints for stratifying laboratory variables in CTP have never been validated. OBJECTIVE: The objective of this study was to identify evidence-based cutpoints for the CTP laboratory subscores to improve its predictive capacity for transplant-free survival. DESIGN: Retrospective observational study. DATA SOURCE: Using a cohort of 30,897 cirrhotic US Veteran patients with at least 5 years of follow-up, we performed Cox proportional hazard survival model iterations varying the upper and lower cutpoints for INR, total bilirubin and albumin CTP subscores. Cutpoints yielding the highest Harrell's C-statistics for concordance with transplant-free survival were incorporated into a modified CTP (mCTP) score. Validation of the mCTP was performed at multiple time frames within the follow-up period of the cohort and within subsets defined by disease etiology. RESULTS: Modification of CTP cutpoints increased the Harrell's C-statistic for age- and gender-adjusted Cox proportional hazard models from 0.701 +/- 0.002 to 0.709 +/- 0.002 and the risk ratio per unit change from 1.49 (1.48-1.50) to 1.53 (1.52-1.54). The modified cutpoints showed superiority in predicting 5-year transplant-free survival in various disease etiology subgroups. A mCTP substituting serum creatinine for INR performed superiorly for predicting 5-year transplant-free survival. CONCLUSION: We propose an evidence-based recalibration of CTP score cutpoints that optimizes this model's capacity to predict transplant-free survival in patients with cirrhosis. The CTP score remains the best predictor of 5-year overall and transplant-free survival in patients with cirrhosis. PMID- 27405991 TI - Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection. AB - OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. METHODS: We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. RESULTS: Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95 % CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95 % CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95 % CI 1.3-12.4). CONCLUSIONS: The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients. PMID- 27405993 TI - Multivitamin and mineral supplements in pregnancy are unnecessary expense, review finds. PMID- 27405992 TI - Plant delta15 N reflects the high landscape-scale heterogeneity of soil fertility and vegetation productivity in a Mediterranean semiarid ecosystem. AB - We investigated the magnitude and drivers of spatial variability in soil and plant delta15 N across the landscape in a topographically complex semiarid ecosystem. We hypothesized that large spatial heterogeneity in water availability, soil fertility and vegetation cover would be positively linked to high local-scale variability in delta15 N. We measured foliar delta15 N in three dominant plant species representing contrasting plant functional types (tree, shrub, grass) and mycorrhizal association types (ectomycorrhizal or arbuscular mycorrhizal). This allowed us to investigate whether delta15 N responds to landscape-scale environmental heterogeneity in a consistent way across species. Leaf delta15 N varied greatly within species across the landscape and was strongly spatially correlated among co-occurring individuals of the three species. Plant delta15 N correlated tightly with soil delta15 N and key measures of soil fertility, water availability and vegetation productivity, including soil nitrogen (N), organic carbon (C), plant-available phosphorus (P), water-holding capacity, topographic moisture indices and normalized difference vegetation index. Multiple regression models accounted for 62-83% of within-species variation in delta15 N across the landscape. The tight spatial coupling and interdependence of the water, N and C cycles in drylands may allow the use of leaf delta15 N as an integrative measure of variations in moisture availability, biogeochemical activity, soil fertility and vegetation productivity (or 'site quality') across the landscape. PMID- 27405994 TI - The Role of Gender in Chagas Disease Prevention and Control in Honduras: An Analysis of Communication and Collaboration Networks. AB - In Honduras, where Chagas disease is a serious health and environmental concern, prevention measures face the challenge of achieving widespread and long-term sustainable adoption by communities. The article integrates social network analysis and a gender-sensitive approach to understand the role of men and women in the implementation of a community-level intervention, based on the adoption of housing improvements to reduce the presence of the insect vector. A total of 108 people in the community of El Salitre were interviewed. Data were collected on socio-demographic characteristics, participation in project activities, communication and collaboration networks related to Chagas disease prevention, knowledge of Chagas disease, and adoption of housing improvements techniques. Communication mostly occurred between the same gender individuals and was associated with knowledge of Chagas disease. Socioeconomic status, Chagas disease knowledge, and collaboration with men were associated with women adopting housing improvements. For men, however, participation in project activities, formal education, and collaboration with women were associated with adoption. These findings suggest that men and women were driven by distinct concerns, interests, and motivations when adopting new Chagas disease prevention strategies. Participatory community interventions that seek to generate health knowledge and foster collaborations to reduce health risk should address gender differences. PMID- 27405995 TI - The development of malaria diagnostic techniques: a review of the approaches with focus on dielectrophoretic and magnetophoretic methods. AB - The large number of deaths caused by malaria each year has increased interest in the development of effective malaria diagnoses. At the early-stage of infection, patients show non-specific symptoms or are asymptomatic, which makes it difficult for clinical diagnosis, especially in non-endemic areas. Alternative diagnostic methods that are timely and effective are required to identify infections, particularly in field settings. This article reviews conventional malaria diagnostic methods together with recently developed techniques for both malaria detection and infected erythrocyte separation. Although many alternative techniques have recently been proposed and studied, dielectrophoretic and magnetophoretic approaches are among the promising new techniques due to their high specificity for malaria parasite-infected red blood cells. The two approaches are discussed in detail, including their principles, types, applications and limitations. In addition, other recently developed techniques, such as cell deformability and morphology, are also overviewed in this article. PMID- 27405996 TI - Physical examination findings and their relationship with performance-based function in adults with knee osteoarthritis. AB - BACKGROUND: Many physical examination (PE) maneuvers exist to assess knee function, none of which are specific to knee osteoarthritis (KOA). The Osteoarthritis Research Society International also recommends the use of six functional performance measures to assess function in adults with KOA. While earlier studies have examined the relationship between PE findings and self reported function or PE findings and select performance tests in adults with knee pain and KOA, few have examined the all three types of measures. This cross sectional study specifically examines the relationships between results of PE findings, functional performance tests and self-reported function in adults with symptomatic KOA. METHODS: We used baseline PE data from a prospective randomized controlled trial in 87 participants aged >=40 years with symptomatic and radiographic KOA. The PE performed by three experienced physical therapists included: muscle assessment, function and special tests. Participants also completed functional performance tests and the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Multivariate linear regression identified contributions of PE findings towards functional performance and WOMAC scores, adjusting for age and gender. RESULTS: Participants' mean age was 60.4 years (SD = 10.5), mean disease duration was 8.4 years (SD = 10.1) and 27 participants had varus knee alignment. Mean WOMAC pain and function scores were 211 (SD = 113) and 709 (SD = 394), respectively. Weakness was present in major hip and knee muscles. Seventy-nine participants had a positive Ely's, 65 a positive Waldron and 49 a positive Grind. Mean 6-min walk was 404 m (SD = 83) and mean Berg Balance was 53 (SD = 4). Regression analysis identified positive findings on 5 special tests (P < 0.05) as indicative of poorer 6 min walk. Positive Apley's was associated (P < 0.05) with slower 20 m walk and a positive Ober with poorer balance scores (P < 0.05). CONCLUSIONS: Diminished hip muscle strength and flexibility, and patella dysfunction were prevalent in these adults with symptomatic KOA. Results of functional performance tests suggest balance and walking ability are impaired and are associated with PE findings of muscle length imbalance, hip muscle weakness and patella dysfunction. None of the PE measures were associated with self reported function. Therefore, performance-based test results may be more useful in informing rehabilitation interventions. PMID- 27405999 TI - Unique properties of C,C'-linked nido-biscarborane tetraanions. Synthesis, structure and bonding of ruthenium monocarbollide via unprecedented cage carbon extrusion. AB - Four reaction pathways have been found in the reaction of a C,C'-linked nido biscarborane tetraanionic salt with [Ru(p-cymene)Cl2]2, leading to the isolation and structural characterization of redox, triple cage B-H oxidative addition, cage expansion and cage carbon extrusion products. Among these, the unprecedented cage carbon extrusion results in the formation of a new 6pi-electron carboranyl ligand [C2B10H10](2-). The bonding interactions between this ligand and the Ru(ii) center have also been discussed on the basis of DFT calculations. PMID- 27405998 TI - The visual properties of proximal and remote distractors differentially influence reaching planning times: evidence from pro- and antipointing tasks. AB - The saccade literature has consistently reported that the presentation of a distractor remote to a target increases reaction time (i.e., the remote distractor effect: RDE). As well, some studies have shown that a proximal distractor facilitates saccade reaction time. The lateral inhibition hypothesis attributes the aforementioned findings to the inhibition/facilitation of target selection mechanisms operating in the intermediate layers of the superior colliculus (SC). Although the impact of remote and proximal distractors has been extensively examined in the saccade literature, a paucity of work has examined whether such findings generalize to reaching responses, and to our knowledge, no work has directly contrasted reaching RTs for remote and proximal distractors. To that end, the present investigation had participants complete reaches in target only trials (i.e., TO) and when distractors were presented at "remote" (i.e., the opposite visual field) and "proximal" (i.e., the same visual field) locations along the same horizontal meridian as the target. As well, participants reached to the target's veridical (i.e., propointing) and mirror-symmetrical (i.e., antipointing) location. The basis for contrasting pro- and antipointing was to determine whether the distractor's visual- or motor-related activity influence reaching RTs. Results demonstrated that remote and proximal distractors, respectively, increased and decreased reaching RTs and the effect was consistent for pro- and antipointing. Accordingly, results evince that the RDE and the facilitatory effects of a proximal distractor are effector independent and provide behavioral support for the contention that the SC serves as a general target selection mechanism. As well, the comparable distractor-related effects for pro- and antipointing trials indicate that the visual properties of remote and proximal distractors respectively inhibit and facilitate target selection. PMID- 27405997 TI - Vestibular ablation and a semicircular canal prosthesis affect postural stability during head turns. AB - In our study, we examined postural stability during head turns for two rhesus monkeys: one animal study contrasted normal and mild bilateral vestibular ablation and a second animal study contrasted severe bilateral vestibular ablation with and without prosthetic stimulation. The monkeys freely stood, unrestrained on a balance platform and made voluntary head turns between visual targets. To quantify each animals' posture, motions of the head and trunk, as well as torque about the body's center of mass, were measured. In the mildly ablated animal, we observed less foretrunk sway in comparison with the normal state. When the canal prosthesis provided electric stimulation to the severely ablated animal, it showed a decrease in trunk sway during head turns. Because the rhesus monkey with severe bilateral vestibular loss exhibited a decrease in trunk sway when receiving vestibular prosthetic stimulation, we propose that the prosthetic electrical stimulation partially restored head velocity information. Our results provide an indication that a semicircular canal prosthesis may be an effective way to improve postural stability in patients with severe peripheral vestibular dysfunction. PMID- 27406000 TI - Energy expenditure and physiological responses during walking on a treadmill and moving on the Torqway vehicle. AB - PURPOSE: One of the new products which can be used to increase physical activity and energy expenditure is the Torqway vehicle, powered by the upper limbs. The aim of this study was to (1) assess the usefulness and repeatability of the Torqway vehicle for physical exercise, (2) compare energy expenditure and physiological responses during walking on a treadmill and during physical effort while moving on the Torqway at a constant speed. METHODS: The participants (11 men, aged 20.2 +/- 1.3) performed the incremental test and submaximal exercises (walking on the treadmill and moving on the Torqway vehicle at the same speed). RESULTS: Energy expenditure during the exercise on the Torqway was significantly higher (p = 0.001) than during the walking performed at the same speed. The intensity of the exercise performed on the Torqway expressed as %VO2max and %HRmax was significantly ( p < 0.001) higher than during walking (respectively: 35.0 +/- 6.0 vs. 29.4 +/- 7.4 %VO2max and 65.1 +/- 7.3 vs. 47.2 +/- 7.4 %HRmax). CONCLUSIONS: Exercise on the Torqway vehicle allows for the intensification of the exercise at a low movement speed, comparable to walking. Moving on the Torqway vehicle could be an effective alternative activity for physical fitness and exercise rehabilitation programs. PMID- 27406001 TI - Current available strategies to mitigate greenhouse gas emissions in livestock systems: an animal welfare perspective. AB - Livestock production is a major contributor to greenhouse gas (GHG) emissions, so will play a significant role in the mitigation effort. Recent literature highlights different strategies to mitigate GHG emissions in the livestock sector. Animal welfare is a criterion of sustainability and any strategy designed to reduce the carbon footprint of livestock production should consider animal welfare amongst other sustainability metrics. We discuss and tabulate the likely relationships and trade-offs between the GHG mitigation potential of mitigation strategies and their welfare consequences, focusing on ruminant species and on cattle in particular. The major livestock GHG mitigation strategies were classified according to their mitigation approach as reducing total emissions (inhibiting methane production in the rumen), or reducing emissions intensity (Ei; reducing CH4 per output unit without directly targeting methanogenesis). Strategies classified as antimethanogenic included chemical inhibitors, electron acceptors (i.e. nitrates), ionophores (i.e. Monensin) and dietary lipids. Increasing diet digestibility, intensive housing, improving health and welfare, increasing reproductive efficiency and breeding for higher productivity were categorized as strategies that reduce Ei. Strategies that increase productivity are very promising ways to reduce the livestock carbon footprint, though in intensive systems this is likely to be achieved at the cost of welfare. Other strategies can effectively reduce GHG emissions whilst simultaneously improving animal welfare (e.g. feed supplementation or improving health). These win-win strategies should be strongly supported as they address both environmental and ethical sustainability. In order to identify the most cost-effective measures for improving environmental sustainability of livestock production, the consequences of current and future strategies for animal welfare must be scrutinized and contrasted against their effectiveness in mitigating climate change. PMID- 27406003 TI - Cryopreservation of Atlantic salmon Salmo salar sperm: effects on sperm physiology. AB - The objective of this study was to determine the effect of freezing on the function in Atlantic salmon Salmo salar spermatozoa. The semen was frozen in Cortland's medium + 1.3M dimethyl sulphoxide + 0.3M glucose + 2% bovine serum albumin (final concentration) in a ratio of 1:3 (semen:cryoprotectant) as the treatment (T) and fresh semen as the control (F). Straws of 0.5 ml of sperm suspension were frozen in 4 cm of N2 L. They were thawed in a thermoregulated bath (40 degrees C). After thawing, the percentage of spermatozoa with fragmented DNA [transferase dUTP (deoxyuridine triphosphate) nick-end labelling (TUNEL)], plasma membrane integrity (SYBR-14/PI) and mitochondrial membrane potential (DeltaPsiMMit, JC-1) were evaluated by flow cytometry and motility was evaluated by optical microscope under stroboscopic light. The fertilization rates of the control and treatment semen were tested at a sperm density of 1.5 * 10(7) spermatozoa oocyte(-1) , by observation of the first cleavages after 16 h incubation at 10 degrees C. In the cryopreserved semen (T), the mean +/- s.d. DNA fragmentation was 4.8 +/- 2.5%; plasma membrane integrity 75.2 +/- 6.3%; mitochondrial membrane potential 51.7 +/- 3.6%; motility 58.5 +/- 5.3%; curved line velocity (VCL ) 61.2 +/- 17.4 um s(-1) ; average-path velocity (VAP ) 50.1 +/- 17.3 um s(-1) ; straight-line velocity (VSL ) 59.1 +/- 18.4 um s(-1) ; fertilization rate 81.6 +/- 1.9%. There were significant differences in the plasma membrane integrity, mitochondrial membrane potential, motility, fertilization rate, VCL , VAP and VSL compared with the controls (P < 0.05). Also the mitochondrial membrane potential correlated with motility, fertilization rate, VCL and VSL (r = 0.75; r = 0.59; r = 0.77 and r = 0.79, respectively; P < 0.05); and the fertilization rate correlated with VCL and VSL (r = 0.59 and r = 0.55, respectively). PMID- 27406004 TI - A Kinetic/Thermodynamic Origin of Regular Chiral Fluctuation or Symmetry Breaking Unique to Preferential Enrichment. AB - The kinetic/thermodynamic origin of preferential enrichment (PE), which is a spontaneous enantiomeric resolution phenomenon applicable to racemic crystals, is described. The mechanism of PE, which was unveiled with respect to the first generation of chiral organic compounds showing PE, has been interpreted in terms of a nonlinear complexity phenomenon including two unique processes: a solvent assisted solid-to-solid polymorphic transition and subsequent selective redissolution of the excess one enantiomer from the transformed disordered crystals into the mother liquor. The present works confirm that PE takes place because of the unique nonlinear solubility properties of the two enantiomers after the occurrence of a polymorphic transition under PE crystallization conditions at high supersaturation. Furthermore, a ternary phase diagram that is consistent with the mechanism of PE is proposed. PMID- 27406002 TI - BMP and retinoic acid regulate anterior-posterior patterning of the non-axial mesoderm across the dorsal-ventral axis. AB - Despite the fundamental importance of patterning along the dorsal-ventral (DV) and anterior-posterior (AP) axes during embryogenesis, uncertainty exists in the orientation of these axes for the mesoderm. Here we examine the origin and formation of the zebrafish kidney, a ventrolateral mesoderm derivative, and show that AP patterning of the non-axial mesoderm occurs across the classic gastrula stage DV axis while DV patterning aligns along the animal-vegetal pole. We find that BMP signalling acts early to establish broad anterior and posterior territories in the non-axial mesoderm while retinoic acid (RA) functions later, but also across the classic DV axis. Our data support a model in which RA on the dorsal side of the embryo induces anterior kidney fates while posterior kidney progenitors are protected ventrally by the RA-catabolizing enzyme Cyp26a1. This work clarifies our understanding of vertebrate axis orientation and establishes a new paradigm for how the kidney and other mesodermal derivatives arise during embryogenesis. PMID- 27406005 TI - Cancer patients' use of primary care out-of-hours services: a cross-sectional study in Norway. AB - OBJECTIVE: To investigate how cancer patients in Norway use primary care out-of hours (OOH) services and describe different contact types and procedures. DESIGN: A retrospective cross-sectional registry study using a billing registry data source. SETTING: Norwegian primary care OOH services in 2014. SUBJECTS: All patients' contacts in OOH services in 2014. Cancer patients were identified by ICPC-2 diagnosis. MAIN OUTCOME MEASURES: Frequency of cancer patients' contacts with OOH services, contact types, diagnoses, procedures, and socio-demographic characteristics. RESULTS: In total, 5752 cancer patients had 20,220 contacts (1% of all) in OOH services. Half of the contacts were cancer related. Cancer in the digestive (22.9%) and respiratory (18.0%) systems were most frequent; and infection/fever (21.8%) and pain (13.6%) most frequent additional diagnoses. A total of 4170 patients had at least one cancer-related direct contact; of these, 64.5% had only one contact during the year. Cancer patients had more home visits and more physicians' contact with municipal nursing services than other patients, but fewer consultations (p < 0.001). Patients in the least central municipalities had significantly more contacts than more central municipalities (p < 0.001). CONCLUSION: There was no indication of overuse of OOH services by cancer patients in Norway, which could indicate good quality of cancer care in general. KEY POINTS Many are concerned about unnecessary use of emergency medical services for non-urgent conditions. * There was no indication of overuse of out-of-hours services by cancer patients in Norway. * Cancer patients had relatively more home visits, physician's contact with the municipal nursing service, and weekend contacts than other patients. * Cancer patients in the least central municipalities had relatively more contacts with out-of-hours services than those in more central municipalities. PMID- 27406006 TI - Concise Review: Salivary Gland Regeneration: Therapeutic Approaches from Stem Cells to Tissue Organoids. AB - The human salivary gland (SG) has an elegant architecture of epithelial acini, connecting ductal branching structures, vascular and neuronal networks that together function to produce and secrete saliva. This review focuses on the translation of cell- and tissue-based research toward therapies for patients suffering from SG hypofunction and related dry mouth syndrome (xerostomia), as a consequence of radiation therapy or systemic disease. We will broadly review the recent literature and discuss the clinical prospects of stem/progenitor cell and tissue-based therapies for SG repair and/or regeneration. Thus far, several strategies have been proposed for the purpose of restoring SG function: (1) transplanting autologous SG-derived epithelial stem/progenitor cells; (2) exploiting non-epithelial cells and/or their bioactive lysates; and (3) tissue engineering approaches using 3D (three-dimensional) biomaterials loaded with SG cells and/or bioactive cues to mimic in vivo SGs. We predict that further scientific improvement in each of these areas will translate to effective therapies toward the repair of damaged glands and the development of miniature SG organoids for the fundamental restoration of saliva secretion. Stem Cells 2017;35:97-105. PMID- 27406007 TI - Ethical, Legal, and Medical Challenges When a Patient Refuses a Transfer From Rehabilitation to Acute Medical Services. PMID- 27406008 TI - Driving Under the Influence of Opioids. PMID- 27406009 TI - Stenotrophomonas maltophila cellulitis in an immunocompromised patient presenting with purpura, diagnosed on skin biopsy. AB - Stenotrophomas maltophilia is an opportunistic Gram-negative bacillus and an important cause of nosocomial infections, particularly in immunosuppressed individuals. Although infections with this organism are most often in the form of pneumonia, bacteremia and endocarditis, awareness of the impact of S. maltophilia skin infections has been increasing. Here we describe a case of S. maltophilia cellulitis in a 65-year-old man with severe neutropenia and purpuric skin lesions to highlight the critical histopathological findings and correlate them with the clinical manifestations of the skin infection with this organism. Because identification of S. maltophilia can be challenging and infections are difficult to manage, this case illustrates essential considerations regarding the multifaceted histopathological, dermatological, clinical and microbiological aspects of the diagnosis and treatment of S. maltophilia cellulitis in a severely immunocompromised patient. Cognizance of the increasing incidence of nosocomial infections with uncommon microorganisms such as S. maltophilia is necessary when presented with atypical cutaneous manifestations, particularly in immunocompromised patients. PMID- 27406010 TI - IgE-dependent mechanism and successful desensitization of erythritol allergy. PMID- 27406011 TI - The experiences of survivors and trauma counselling service providers in northern Uganda: Implications for mental health policy and legislation. AB - Previous research in northern Uganda found high levels of trauma-related difficulties amongst the conflict-affected population. There is international evidence that psychological therapy can reduce depression, as one of the psychological effects of trauma, but very limited literature regarding the experiences of trauma counselling in Sub-Saharan Africa. The current British Academy and Leverhulme-funded research investigated the experiences of service users and providers of trauma services in Kitgum and Gulu, northern Uganda. It also examined their implications for mental health policy and legislation. A decision was made to utilise qualitative methodology to highlight the in-depth experiences of participants. The researcher's carried out interviews with 10 women and 10 men survivors attending trauma services in Kitgum and Gulu. The researchers also interviewed 15 key informants in Kitgum, Gulu and Kampala including trauma counselling service providers, ministers, cultural leaders and mental health professionals. The authors report the findings of the research based on thematic analysis of the interviews. Themes included the experiences of survivors, bearing witness and instilling hope, constraints to service provision, stigma and abuse, holistic approach, service providers doing their best, specialist populations, limited understanding, training and skills development, gaps in service provision and mental health policy and legislation. The interviews resulted in a clear indication that counselling and medication was valued by service users, and that service providers felt the treatments that were provided improved depression, and increased empowerment and engagement in social activities. However, the authors argue that there was a limit to the benefits that could be achieved without using the holistic approach that the survivors requested. Thus, in cases of trauma arising from conflict, there is a clear need for the state to ensure reparation and/or justice for the atrocities witnessed by and perpetrated against survivors. This might include the provision of compensation, which would help to meet social needs and reduce feelings of shame and anger. PMID- 27406012 TI - Effect of moderate or high intensity exercise on hypothyroid rats exposed to acute stress. AB - BACKGROUND: There are contradictory results about stress response in hypothyroidism and in exercising with variant intensities. We aimed to investigate the potential anxiolytic and protective effects of different intensities of exercise on acute psychological stress in hypothyroidism. METHODS: Rats (N.=48) were divided as sedentary, moderate intensity (MIE) and high intensity exercise (HIE) groups. Rats were administered intraperitoneally with 6 n-propyl-2-thiouracil (PTU, 10 mg/kg) for 15 days to induce hypothyroidism. Starting by the 3rd week, treadmill exercise was performed moderately (30 min/day) or at high intensity (60 min/day) for 6 weeks, 5 days/week. At the end of the 8th week, exposure to water avoidance stress was used for induction of acute stress. Anxiety-like behavior was determined by holeboard test before and after stress inductions. Serum IL-1beta and IL-6 assays, and myeloperoxidase activity (MPO), malondialdehyde (MDA), and glutathione (GSH) measurements, and histological analysis of heart, liver, stomach and small intestine were made. RESULTS: All groups showed increased anxiety-like behavior following acute stress induction. After acute stress induction, increased MPO and MDA levels in heart and elevated MPO activity in liver were inhibited in PTU-treated HIE group. In MIE rats, increased MPO and declined GSH levels of the gastric tissue and small intestine, and elevated MDA levels of gastric tissue were reversed in PTU-treated MIE group. Major histological changes that occurred by both intensities of exercise under stress condition were improved by PTU. CONCLUSIONS: Our results indicate that hypothyroid state may be protective against stress- and exhaustive exercise-induced oxidative damage. PMID- 27406013 TI - Development of maximal speed sprinting performance with changes in vertical, leg and joint stiffness. AB - BACKGROUND: This study aimed to clarify the changes in stiffness variables when maximal speed sprinting performance was developed through long-term training. METHODS: Nine well-trained male athletes performed maximal effort 60-m sprints before and after the completion of six months of winter training. In both experiments, sprinting motion at maximal speed was recorded with a high-speed camera and simultaneously ground reaction force (GRF) was measured. Spatiotemporal and stiffness variables were then calculated. RESULTS: Sprinting speed was significantly developed (P=0.001) through longer step length (P=0.049). While the leg stiffness did not change (from -539+/-126 to -558+/-180 N/kg/m) (P=0.686), the vertical stiffness significantly increased (P=0.001) from -1507+/ 346 to -2357+/-704 N/kg/m due to increase and decrease in vertical GRF and descent of whole body center of gravity, respectively. Moreover, whereas knee joint stiffness remained constant (from -0.228+/-0.080 to -0.213+/-0.084 Nm/kg/ degrees ) (P=0.448), ankle joint stiffness was significantly developed (P=0.002) from -0.165+/-0.031 to -0.210+/-0.032 Nm/kg/ degrees due to a respective increase and decrease in ankle plantarflexion moment and ankle dorsiflexion angle. CONCLUSIONS: The results demonstrate that the development of maximal speed sprinting performance through longer step length is accompanied by increases in vertical and ankle joint stiffness, and this shows the importance of vertical and ankle stiffness for improving maximal speed sprinting performance. Findings of this study may assist with the planning of training programs for athletes. PMID- 27406014 TI - Investigating the Debate: Does DHEA Alter Food Intake? AB - Treatment with dehydroepiandrosterone (DHEA) leads to a decrease in the fat stores of a variety of rodent models of obesity. However, whether DHEA affects food intake and whether such changes are important at reducing obesity is not settled. Some state that food intake is not altered by DHEA and that the effect on weight gain is caused by induced inefficiencies in metabolism. Others report that DHEA leads to a prompt decrease in caloric consumption and that this change is important in causing weight loss. In this commentary the data supporting both sides of this controversy are reviewed. Analysis suggests that these radically different conclusions are caused by investigators using studies of different experimental design; shorter experiments emphasize DHEA's effects on food intake, while longer experiments tend to emphasize DHEA's metabolic effects. In addition the way the investigators normalize their food intake results for differences in animal size may influence their analyses. It is concluded that DHEA exerts both a metabolic effect and an effect on caloric intake and that both are involved in medicating changes in fat stores of obese animals. PMID- 27406015 TI - Short-Term Social Isolation Does Not Reduce Elevated Plus-Maze Exploration in Early Protein Malnourished Rats. AB - An increased number of visits and time spent in the open arms of the elevated plus-maze by malnourished rats has been used as indicative of lower anxiety or higher impulsiveness. In order to study how this behavior profile responds to an anxiogenic procedure (short-term social isolation), control (16% protein) and malnourished (6% protein) rats were socially isolated prior to the test in the maze. Litters (dam plus 6 male and 2 female pups) were fed the diets from birth to 49 days of age. From 50 days on, all rats were fed a lab chow diet. Social isolation consists in removing the rats from the group and placing them in individual cages for 2 h before the test. During the test each rat was individually placed on the center of the maze and allowed to explore for 5 min. The results showed higher open arms exploration and lower attempts to enter open arms by the malnourished rats than by the controls. Social isolation decreased open arm exploration and increased time spent on the central platform in control animals, but had no effect on the malnourished rats. The results reinforce the lower anxiety or higher impulsiveness of malnourished rats, as well as the anxiogenic effect of social isolation in control rats. However, the malnourished rats were unresponsive to the anxiogenic effects of social isolation, indicating that protein deficiency early in life not only induces lower anxiety or higher impulsiveness in the maze, but also changes the behavior of these animals in response to another environmentally-induced procedure of anxiety (social isolation). PMID- 27406016 TI - Identification of Enterostatin and the Relation between Lipase and Colipase in Various Species. AB - Enterostatin, the N-terminal activation peptide of pancreatic procolipase, has been identified in three different forms in rat: VPDPR (Val-Pro-Asp-Pro-Arg), APGPR (Ala-Pro-Gly-Pro-Arg) and VPGPR (Val-Pro-Gly-Pro-Arg). We investigated the possibility for a species to have several isoforms of enterostatin. Pancreas was purified from four different species (rat, mouse, cat and pig) and the enterostatin sequences were identified. At the same time, the activities of pancreatic lipase and colipase were measured. In rat and mouse pancreas APGPR was the only form of enterostatin identified. The colipase activity was 188 +/- 25 U/mg protein in rat and 189 +/- 16 U/mg in mouse and the lipase activity 354 +/- 33 U/mg and 292 +/- 19 U/mg respectively. Rat and mouse had a colipase/lipase ratio close to 0.5. In pancreas from cat and pig we only detected the form VPDPR (Val-Pro-Asp-Pro-Arg). We found the colipase activity in cat to be 493 +/- 92 U/mg, while the lipase activity was three times lower, 167 +/- 18 U/mg. Pig pancreas concentrations of colipase was 110 +/- 8 U/mg and of lipase 38 +/- 5 U/mg. In both cat and pig the colipase/lipase ratio was close to 3. This suggests that colipase might have an additional role than to restore the activity of lipase. Our hypothesis is that an overproduction of colipase and hence also enterostatin is involved in the regulation of fat metabolism. PMID- 27406017 TI - Dietary Tyrosine Protects Striatal Dopamine Receptors from the Adverse Effects of REM Sleep Deprivation. AB - L-Tyrosine is a non-essential amino acid that is produced as an intermediary metabolite in the conversion of phenylalanine to 3,4-dihyroxyphenylalanine (DOPA), and is a precursor of the neurotransmitter dopamine. In previous studies, tyrosine pretreatment was shown to protect against the neurochemical and behavioral deficits of acute stress caused by tail shock or cold exposure in rodents. The present study addressed the hypothesis that tyrosine administration may be an effective counter-measure to dopamine-mediated behaviors induced by rapid eye-movement sleep deprivation (RSD). In order to test the hypothesis, Sprague-Dawley rats were divided into 9 treatment groups: RSD-treated rats on normal-protein diet (20% casein: 1% tyrosine, 1% valine); tank control (TC) rats on a normal diet; cage control (CC) rats on normal diet; RSD-treated rats on 4% tyrosine diet; TC rats on 4% tyrosine diet; CC rats on 4% tyrosine diet; RSD treated rats on 4% valine diet; TC rats on 4% valine diet; CC rats on 4% valine diet. In the RSD group receiving tyrosine, there was no apparent change in Bmax for binding of the dopamine D2 receptor ligand [(3)H]YM-09151-2 in the striata as compared to the respective TC and CC groups; whereas RSD-treated rats maintained on the normal diet and valine supplementation demonstrated expected increases in Bmax for ligand binding. The TC group on the tyrosine diet showed attenuated catalepsy compared to the corresponding CC group, while the RSD group consuming tyrosine showed a catalepsy that was significantly increased, and similar to that of cage control animais on a control diet. These data suggest that the tyrosine supplemented diet significantly attenuated RSD-induced changes in striatal dopamine D2 receptors, and the effect appeared sufficient to influence RSD induced behaviors. PMID- 27406018 TI - The Effect of Dietary Polyunsaturated Fatty Acids and Alcohol on Neurotransmitter Levels in Rat Brain. AB - A novel animal model of alcoholism is presented which includes the features of chronic alcohol exposure, repeated withdrawal and a diet limited in essential fatty acids. The model was used to study the effect of these variables on neurotransmitter and theirmetabolites (serotonin, 5-hydroxyindole-3-acetic acid, dopamine, norepinephrine and di-hydroxyphenylacetic acid) concentrations in the brainstem, caudate, cerebellum, cortex and hippocampus of Long-Evans rats. Two novel, nutritionally adequate liquid diet compositions were developed using elements of the AIN-93M and Lieber-DeCarli rodent diets. The basal diet bad low (0.3 en%) levels of the essential fatty acids 18: 2n6 and 18: 3n3 (BASE). The experimental diet (PUFA) was identical to BASE except for the addition of low levels, 0.5 en% each, of arachidonic acid (AA) and docosahexaenoic acid (DHA). Animals on ethanol (EtOH) containing diets (BASE-EtOH and PUFA-EtOH) experienced eight intermittent ethanol withdrawal periods during the three month exposure period. One group of rats were on a continuous alcohol regime (BASE-EtOH(cont.)) with a single withdrawal period at the end of the study. Using the isocaloric pair-feeding technique for liquid diets, the effects of diet, alcohol and withdrawal were studied in 69 (44 were used for neurotransmitter determinations) individually housed rats over ninety days. Neurotransmitter levels were generally higher in the BASE and PUFA groups compared to BASE-EtOH and PUFA-EtOH, respectively. The concentrations of the serotonin metabolite 5-hydroxyindole-3 acetic acid were reduced in all five areas in the brain of the BASE-EtOH animals, given multiple withdrawal periods in comparison to the BASE-EtOH(cont.) group which were administered alcohol in a continuous fashion. Long-chain PUFA, at 1.0 en%, could generally not prevent the neurotransmitter lowering effect of alcohol, but it led to an elevation of these levels in PUFA animals compared with BASE. These results indicate that dietary fatty acids influence neurotransmitter metabolism in the brain. PMID- 27406019 TI - A Preliminary Study of Temperament Among Malnourished Mayan Children. AB - Temperament ratings using a modified Carey Infant Temperament Questionnaire were assessed in marginally malnourished and healthy comparison infants aged 7-13 months. The children were selected from a total of 81 children in this age range living in a rural region of southern Yucatan, Mexico. Eleven marginally malnourished infants whose weights fell between one-half and two standard deviations below local means and 14 comparison children whose weights fell one half to two standard deviations above the local means were included in the study. Lengths did not differ between index and comparison groups. Related temperament categories were statistically grouped into two factors. Factor 1 (Difficult Child), which included approach, mood, threshold, adaptability and rhythmicity, showed a significant nutrition * sex interaction; Factor 2 (Activity) did not distinguish the groups. Comparison boys were viewed as significantly easier than marginally malnourished boys, and they were more adaptable to change and predictable in biological functions. Girls were similar regardless of nutritional status, and their scores were intermediate between those of malnourished and well nourished boys. These findings were not significantly associated with environmental conditions in the home. PMID- 27406020 TI - Moderate Alcohol Intake: Behavioral and Neurochemical Correlates in Rats. AB - A debate is open in the literature concerning the safety of low (dietary) versus high (intoxicating or addicting) alcohol consumption. Epidemiological data do indeed suggest that moderate ethanol intake may have beneficial effects, at least at cardiovascular level. On the other hand there are few data on the effect of low doses ethanol at brain level and few experimental models to investigate it, in spite of a vast literature on the addicting mechanisms. In the last years we have addressed this question by investigating behavioral and neurochemical parameters in rats consuming low ethanol doses, not producing tolerance and dependence, thus mimicking balanced dietary intake of ethanol. Ethanol exposure (3% vol/vol in drinking water for 8 weeks) ameliorates emotional reactivity, evaluated as decrease in ultrasonic calls, and improves learning in animals undergoing a two-way avoidance task. The concomitant measure of neurochemical parameters indicates plastic changes in receptor (dopamine) and post-receptor (protein kinase C) mechanisms. These changes are in some cases qualitatively different from those observed with intoxicating ethanol doses. This model may be useful for the further characterization of the beneficial versus detrimental effect of moderate ethanol consumption at brain level. PMID- 27406021 TI - The Neuropeptide Cyclo(His-Pro) Levels are Increased in Diabetic Ketoacidosis and Fall with Treatment in Parallel with Levels of Glucagon. AB - The importance of insulin deficiency and glucagon excess is recognized as critical in the pathogenesis of diabetic ketoacidosis (DKA). The finding of elevated levels of another gut peptide in DKA with potential relevant physiological effects might renew discussion of the pathogenesis of this disorder. Cyclo(His-Pro) is a gut-brain peptide found in gut of rat and man. In pancreas it is localized to alpha cells. A stereospecific hepatic bonding site has been found. We have shown that cyclo(His-Pro) augments the insulin response to oral glucose in rat by decreasing hepatic insulin clearance. In view of cyclo(His-Pro)'s location in alpha cells, the hepatic binding site and action described, we wondered if levels of cyclo(His-Pro) might be elevated in a hyperglucagonemic state such as DKA and whether these levels might correlate with those of glucagon and other commonly followed parameters in DKA. Plasma was collected from 7 nondiabetic controls and 9 patients in DKA before and after 4, 8, 12, and 24 h of therapy and assayed for glucose, HCO3, anion gap, glucagon and cyclo(His-Pro). Cyclo(His-Pro) levels were higher in DKA patients before therapy than controls (15.6 +/- 3.2 vs. 8.0 +/- 0.2 pmol/ml; p =0.023) as were glucagon levels (201 +/- 4 vs. 56 +/- 5ng/L; p = 0.006). Cyclo(His-Pro) levels fell significantly with treatment (15.6 +/- 3.2 vs 8.1 +/- 1.1; p = 0.024) and in parallel with those of glucagon. We conclude that cyclo(His-Pro) levels are increased in patients with DKA before therapy and fall in parallel with those of glucagon. This represents the first report of altered levels of this peptide in a disease state. PMID- 27406022 TI - A Description of the Appropriate Use of Student's t-Test. AB - This is the second in a series of articles devoted to a simplified description of experimental design, statistical analysis, and interpretation. The present article deals with the proper use of Student's t-test. Examples are provided of nutritional experiments in which a two-tailed Student's t-test may be properly applied and a second example in which the F-test in the analysis of variance is more useful. PMID- 27406024 TI - Automated Classification of Selected Data Elements from Free-text Diagnostic Reports for Clinical Research. AB - OBJECTIVES: In the Multiple Myeloma clinical registry at Heidelberg University Hospital, most data are extracted from discharge letters. Our aim was to analyze if it is possible to make the manual documentation process more efficient by using methods of natural language processing for multiclass classification of free-text diagnostic reports to automatically document the diagnosis and state of disease of myeloma patients. The first objective was to create a corpus consisting of free-text diagnosis paragraphs of patients with multiple myeloma from German diagnostic reports, and its manual annotation of relevant data elements by documentation specialists. The second objective was to construct and evaluate a framework using different NLP methods to enable automatic multiclass classification of relevant data elements from free-text diagnostic reports. METHODS: The main diagnoses paragraph was extracted from the clinical report of one third randomly selected patients of the multiple myeloma research database from Heidelberg University Hospital (in total 737 selected patients). An EDC system was setup and two data entry specialists performed independently a manual documentation of at least nine specific data elements for multiple myeloma characterization. Both data entries were compared and assessed by a third specialist and an annotated text corpus was created. A framework was constructed, consisting of a self-developed package to split multiple diagnosis sequences into several subsequences, four different preprocessing steps to normalize the input data and two classifiers: a maximum entropy classifier (MEC) and a support vector machine (SVM). In total 15 different pipelines were examined and assessed by a ten-fold cross-validation, reiterated 100 times. For quality indication the average error rate and the average F1-score were conducted. For significance testing the approximate randomization test was used. RESULTS: The created annotated corpus consists of 737 different diagnoses paragraphs with a total number of 865 coded diagnosis. The dataset is publicly available in the supplementary online files for training and testing of further NLP methods. Both classifiers showed low average error rates (MEC: 1.05; SVM: 0.84) and high F1 scores (MEC: 0.89; SVM: 0.92). However the results varied widely depending on the classified data element. Preprocessing methods increased this effect and had significant impact on the classification, both positive and negative. The automatic diagnosis splitter increased the average error rate significantly, even if the F1-score decreased only slightly. CONCLUSIONS: The low average error rates and high average F1-scores of each pipeline demonstrate the suitability of the investigated NPL methods. However, it was also shown that there is no best practice for an automatic classification of data elements from free-text diagnostic reports. PMID- 27406023 TI - Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors. AB - Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17alpha hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells. PMID- 27406026 TI - Aurora-A Kinase: A Potent Oncogene and Target for Cancer Therapy. AB - The Aurora kinase family is comprised of three serine/threonine kinases, Aurora A, Aurora-B, and Aurora-C. Among these, Aurora-A and Aurora-B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases has been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis. Aurora kinases therefore represent promising targets for anticancer therapeutics. A number of Aurora kinase inhibitors (AKIs) have been generated; some of which are currently undergoing clinical evaluation. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in promoting tumorigenesis, the recent preclinical and clinical AKI data, and potential alternative routes for Aurora-A kinase inhibition. PMID- 27406027 TI - The discovery of the Amazonian tree flora with an updated checklist of all known tree taxa. AB - Amazonia is the most biodiverse rainforest on Earth, and the debate over how many tree species grow there remains contentious. Here we provide a checklist of all tree species collected to date, and describe spatial and temporal trends in data accumulation. We report 530,025 unique collections of trees in Amazonia, dating between 1707 and 2015, for a total of 11,676 species in 1225 genera and 140 families. These figures support recent estimates of 16,000 total Amazonian tree species based on ecological plot data from the Amazonian Tree Diversity Network. Botanical collection in Amazonia is characterized by three major peaks, centred around 1840, 1920, and 1980, which are associated with flora projects and the establishment of inventory plots. Most collections were made in the 20th century. The number of collections has increased exponentially, but shows a slowdown in the last two decades. We find that a species' range size is a better predictor of the number of times it has been collected than the species' estimated basin-wide population size. Finding, describing, and documenting the distribution of the remaining species will require coordinated efforts at under-collected sites. PMID- 27406028 TI - A Novel Extract of Fenugreek Husk (FenuSMARTTM) Alleviates Postmenopausal Symptoms and Helps to Establish the Hormonal Balance: A Randomized, Double-Blind, Placebo-Controlled Study. AB - Despite the widespread use of hormone replacement therapy, various reports on its side effects have generated an increasing interest in the development of safe natural agents for the management of postmenopausal discomforts. The present randomized, double-blinded, placebo-controlled study investigated the effect of 90-day supplementation of a standardized extract of fenugreek (Trigonella foenum graecum) (FenuSMARTTM), at a dose of 1000 mg/day, on plasma estrogens and postmenopausal discomforts. Eighty-eight women having moderate to severe postmenopausal discomforts and poor quality of life (as evidenced from the scores of Greene Climacteric Scale, short form SF-36(r) and structured medical interview) were randomized either to extract-treated (n = 44) or placebo (n = 44) groups. There was a significant (p < 0.01) increase in plasma estradiol (120%) and improvements on various postmenopausal discomforts and quality of life of the participants in the extract-treated group, as compared with the baseline and placebo. While 32% of the subjects in the extract group reported no hot flashes after supplementation, the others had a reduction to one to two times per day from the baseline stages of three to five times a day. Further analysis of haematological and biochemical parameters revealed the safety of the extract and its plausible role in the management of lipid profile among menopausal women. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406029 TI - Green and selective polycondensation methods toward linear sorbitol-based polyesters: enzymatic versus organic and metal-based catalysis. AB - Renewable polyesters derived from a sugar alcohol (i.e., sorbitol) were synthesized by solvent-free polycondensation. The aim was to prepare linear polyesters with pendant hydroxyl groups along the polymer backbone. The performance of the sustainable biocatalyst SPRIN liposorb CALB [an immobilized form of Candida antarctica lipase B (CALB); SPRIN technologies] and the organo base catalyst 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were compared with two metal-based catalysts: dibutyl tin oxide (DBTO) and scandium trifluoromethanesulfonate [also known as scandium triflate, Sc(OTf)3 ]. For the four catalytic systems, the efficiency and selectivity for the incorporation of sorbitol were studied, mainly using (13) C and (31) P NMR spectroscopies, whereas side reactions, such as ether formation and dehydration of sorbitol, were evaluated using MALDI-TOF-MS. Especially the biocatalyst SPRIN liposorb CALB succeeded in incorporating sorbitol in a selective way without side reactions, leading to close-to-linear polyesters. By using a renewable hydroxyl-reactive curing agent based on l-lysine, transparent and glossy poly(ester urethane) networks were successfully synthesized offering a tangible example of bio-based coatings. PMID- 27406030 TI - Fertility of patients with polycystic ovary syndrome undergoing in vitro fertilization by age. AB - OBJECTIVE: To evaluate outcomes of in vitro fertilization (IVF) among patients with polycystic ovary syndrome (PCOS) by age. METHODS: In a retrospective study, data were retrieved for patients with PCOS (Rotterdam 2003 criteria) and individuals with tubal factor infertility who underwent IVF at a center in Seoul, South Korea, between January 2003 and August 2012. IVF outcomes were compared by age group (A: 30-32 years; B: 33-35 years; C: 36-38 years; D: 39-41 years). RESULTS: The analysis included 307 women with PCOS and 364 with tubal factor infertility. There was a significant difference between women with PCOS and those with tubal infertility factor in the live birth rate in group B (41.3% vs 28.6%, P=0.038) and in group C (40.4% vs 15.1%, P=0.002). Among women with PCOS, no significant differences in number of retrieved oocytes were observed between the age groups (18.8 +/- 9.6, 19.1 +/- 10.0, 17.7 +/- 7.5, and 17.0 +/- 13.8). However, the clinical pregnancy rate was significantly lower in group D than in group C (47.2% vs 18.8%, P=0.042). CONCLUSION: Fertility in patients with PCOS was maintained until age 38 years using IVF. Thereafter, the pregnancy rate decreased, although the number of oocytes retrieved by IVF remained stable. PMID- 27406031 TI - Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan. AB - Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are liver specific autoimmune conditions that are characterized by chronic hepatic damage and often lead to cirrhosis and hepatic failure. Specifically, the protein tyrosine phosphatase N22 (PTPN22) gene encodes the lymphoid protein tyrosine phosphatase, which acts as a negative regulator of T-cell receptor signaling. A missense single nucleotide polymorphism (SNP) (rs2476601) in PTPN22 has been linked to numerous autoimmune diseases in Caucasians. In the present series, nine SNPs in the PTPN22 gene were analyzed in 166 patients with AIH, 262 patients with PBC, and 322 healthy controls in the Japanese population using TaqMan assays. Although the functional rs3996649 and rs2476601 were non-polymorphic in all subject groups, the frequencies of the minor alleles at rs1217412, rs1217388, rs1217407, and rs2488458 were significantly decreased in AIH patients as compared with controls (all Pc < 0.05). There were no significant relationships with PTPN22 SNPs in PBC patients. Interestingly, the AAGTCCC haplotype was significantly associated with resistance to both AIH (odds ratio [OR] = 0.58, P = 0.0067) and PBC (OR = 0.58, P = 0.0048). SNPs in the PTPN22 gene may therefore play key roles in the genetic resistance to autoimmune liver disease in the Japanese. PMID- 27406032 TI - Exploring functional data analysis and wavelet principal component analysis on ecstasy (MDMA) wastewater data. AB - BACKGROUND: Wastewater-based epidemiology (WBE) is a novel approach in drug use epidemiology which aims to monitor the extent of use of various drugs in a community. In this study, we investigate functional principal component analysis (FPCA) as a tool for analysing WBE data and compare it to traditional principal component analysis (PCA) and to wavelet principal component analysis (WPCA) which is more flexible temporally. METHODS: We analysed temporal wastewater data from 42 European cities collected daily over one week in March 2013. The main temporal features of ecstasy (MDMA) were extracted using FPCA using both Fourier and B spline basis functions with three different smoothing parameters, along with PCA and WPCA with different mother wavelets and shrinkage rules. The stability of FPCA was explored through bootstrapping and analysis of sensitivity to missing data. RESULTS: The first three principal components (PCs), functional principal components (FPCs) and wavelet principal components (WPCs) explained 87.5-99.6 % of the temporal variation between cities, depending on the choice of basis and smoothing. The extracted temporal features from PCA, FPCA and WPCA were consistent. FPCA using Fourier basis and common-optimal smoothing was the most stable and least sensitive to missing data. CONCLUSION: FPCA is a flexible and analytically tractable method for analysing temporal changes in wastewater data, and is robust to missing data. WPCA did not reveal any rapid temporal changes in the data not captured by FPCA. Overall the results suggest FPCA with Fourier basis functions and common-optimal smoothing parameter as the most accurate approach when analysing WBE data. PMID- 27406034 TI - Frameshift Mutation of MED25, a Transcription Regulator, and its Mutational Heterogeneity in Colorectal Cancers. PMID- 27406033 TI - A 'compare and contrast' exercise: wrapping versus personalised external aortic root support (PEARS). AB - Wrapping of the aorta and personalised external aortic root support (PEARS) both have the purpose of preventing further expansion of the ascending aorta in order to reduce the risk of aortic dissection and to spare the patient the disastrous consequences of aortic rupture. For the first time, Plonek and colleagues have reported systematically the CT appearances of a series of cases of wrapping. They illustrate the important finding that there are residual spaces between the aorta and the wrap. PEARS by contrast is intimately in contact with the aorta due to its personalised design and is fully incorporated due it construction from a porous mesh. A limitation of PEARS is that it is, of its nature, a planned and elective operation while wrapping can be undertaken during an emergency operation and can be used without prior planning as an intraoperative decision. PMID- 27406035 TI - Client and parent feedback on a Youth Mental Health Service: The importance of family inclusive practice and working with client preferences. AB - In mental health settings, feedback from clients and carers is central to service evaluation, development and delivery. Increasingly, client and carer feedback is considered an integral part of service planning, and recognized as a critical element of the provision of recovery oriented service. This paper outlines the findings of a qualitative evaluation of a Youth Mental Health (YMH) service from the perspective of discharged clients and their parents. The service researcher conducted telephone interviews with 39 parents of discharged clients, and 17 young people themselves. Participants reported positive or mixed experiences with the service. In addition to more generic positive statements about the service, analysis identified two key themes: the importance of 'family inclusive practice' and the importance of 'working with client preferences'. Young people and their parents want to be actively engaged in treatment and have their treatment preferences considered in treatment planning. Participants expressed the importance of "a good fit" between the client and the worker in terms of the clinician's gender, personality and treatment style/modality. While for some participants these themes were raised in the context of service strengths, others identified them as limitations or opportunities for service improvement. The extent to which clients and their parents felt engaged and heard by their allocated clinician is critical to their satisfaction or dissatisfaction with the service, depending on their unique experience. As an outcome of this evaluation, a range of service improvement strategies have been recommended. PMID- 27406036 TI - Health professionals and the early detection of head and neck cancers: a population-based study in a high incidence area. AB - BACKGROUND: In the context of early detection of head and neck cancers (HNC), the aim of this study was to describe how people sought medical consultation during the year prior to diagnosis and the impact on the stage of the cancer. METHODS: Patients over 20 years old with a diagnosis of HNC in 2010 were included from four French cancer registries. The medical data were matched with data regarding uptake of healthcare issued from French National Health Insurance General Regime. RESULTS: In 86.0 % of cases, patients had consulted a general practitioner (GP) and 21.1 % a dentist. Consulting a GP at least once during the year preceding diagnosis was unrelated to Charlson index, age, sex, departement, quintile of deprivation of place of residence. Patients from the 'quite privileged', 'quite underprivileged' and 'underprivileged' quintiles consulted a dentist more frequently than those from the 'very underprivileged' quintile (p = 0.007). The stage was less advanced for patients who had consulted a GP (OR = 0.42 [0.18 0.99]) - with a dose-response effect. CONCLUSIONS: In view of the frequency of consultations, the existence of a significant association between consultations and a localised stage at diagnosis and the absence of a socio-economic association, early detection of HNC by GPs would seem to be the most appropriate way. PMID- 27406037 TI - Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting. AB - Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Kruppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long term expansion regimen prior to transplantation. PMID- 27406038 TI - How Do Forensic Clinicians Decide? A Delphi Approach to Identify Domains Commonly Used in Forensic Juvenile Treatment Planning. AB - Adolescents in forensic care display wide varieties of complex psychiatric, psychological, and contextual problems. Based on large amounts of information, clinicians need to consider, integrate, and prioritize these offender characteristics to construct individual treatment trajectories. So far, scientific knowledge on how these treatment decisions take place is scarce. Current study uses a qualitative design for detecting implicit knowledge of clinicians on which offender characteristics they consider while making treatment decisions. Using the Delphi method, 34 experienced clinicians working in forensic care facilities in the Netherlands were asked about the most important domains of offender characteristics that influence their treatment planning. Eight domains were identified as being crucial in treatment planning: Mental health problems, Personal characteristics, Family, Offense, Motivation, Treatment, School/Work/Housing, and Peers/Spare time. Based on current results, focus on a broad spectrum of individual and contextual characteristics is recommended. Moreover, protective factors and comorbid problems on multiple domains should be considered. PMID- 27406039 TI - Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis. AB - OBJECTIVE: Pancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn's disease, but have also been observed with variable frequencies in patients with UC. In a previous study, we observed a high frequency of primary sclerosing cholangitis (PSC) in patients with anti-GP2-positive UC. We therefore aimed to characterise the role of anti-GP2 in PSC. DESIGN: In an evaluation phase, sera from 138 well-characterised Norwegian patients with PSC were compared with healthy controls (n=52), and patients with UC without PSC (n=62) for the presence of PABs by indirect immunofluorescence. Further, 180 German patients with PSC served as a validation cohort together with 56 cases of cholangiocarcinoma without PSC, 20 of secondary sclerosing cholangitis (SSC) and 18 of autoimmune hepatitis. RESULTS: Anti-GP2 IgA specifically occurred at considerable rates in large bile duct diseases (cholangiocarcinoma=36%, PSC and SSC about 50%). In PSC, anti-GP2 IgA consistently identified patients with poor survival during follow-up (Norwegian/German cohort: p Log Rank=0.016/0.018). Anti GP2 IgA was associated with the development of cholangiocarcinoma in both PSC cohorts, yielding an overall OR of cholangiocarcinoma in patients with anti-GP2 IgA-positive PSC of 5.0 (p=0.001). Importantly, this association remained independent of disease duration, bilirubin level and age. CONCLUSIONS: Anti-GP2 IgA can be hypothesised as a novel marker in large bile duct diseases. In particular, in PSC, anti-GP2 IgA identified a subgroup of patients with severe phenotype and poor survival due to cholangiocarcinoma. Anti-GP2 IgA may therefore be a clinically valuable tool for risk stratification in PSC. PMID- 27406041 TI - Facile one-pot synthesis of unsymmetrical ureas, carbamates, and thiocarbamates from Cbz-protected amines. AB - A novel one-pot synthesis of unsymmetrical ureas, carbamates and thiocarbamates from Cbz-protected amines has been developed. In the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, isocyanates are generated in situ, which facilitate rapid reaction with amines, alcohols, and thiols to afford the corresponding ureas, carbamates and thiocarbamates in high yields. PMID- 27406040 TI - Risk and Outcomes: Are Adolescents Charged with Sex Offenses Different from Other Adolescent Offenders? AB - Juveniles who have committed sexual offenses are subject to specialized treatment and policies based on their assumed unique dangerousness, despite contradictory evidence. Limited information is available regarding risk factors and their relationships to outcomes in this population. The comparative frequency and predictive utility of empirically supported risk factors for general delinquency were examined using data from the Pathways to Desistance study. Adolescent males who committed sexual offenses (n = 127) were compared to adolescent males who committed non-sexual offenses (n = 1021). At the start of the study, the sample ranged in age from 14 to 18 (M = 16.00, SD = 1.12) and self-identified as primarily African American (44 %), Latino (29 %), or White (25 %). Outcomes were measured over 7 years and included general and sexual recidivism, involvement in school and work, and positive relationships with peers and adults. The results indicated a few small differences in the presence of risk factors and their relationship to outcomes, with many similarities. Juveniles who have committed sexual offenses had equivalent general recidivism but higher sexual recidivism, though this rate was low (7.87 %, or 10 of the 127 adolescents who had committed sexual offenses). New clinical and policy approaches may be needed given the similarities between groups. PMID- 27406042 TI - [Percutaneous calcaneal sliding osteotomy]. AB - OBJECTIVES: Correction of calcaneal malalignment as part of a hindfoot correction procedure. INDICATIONS: Varus and valgus malalignment of the calcaneus, increased calcaneal pitch. CONTRAINDICATIONS: Osteoarthritis of the subtalar joint. Fixed and symptomatic deformities of the subtalar joint. SURGICAL TECHNIQUE: After having identified and marked the desired planes of the osteotomy under image intensifier, a percutaneous v-shaped calcaneal osteotomy is performed. The osteotomy allows 3-dimensional correction of the calcaneus by defining the planes of the osteotomy. The procedure allows correction of varus and valgus deformities, as well as a change of the calcaneal pitch. The osteotomy is fixed by percutaneous screws. POSTOPERATIVE MANAGEMENT: Postoperative care includes a 6 week period of partial weight bearing with 10 kg. The ankle joint should be mobilized. After x-ray control of sufficient bone healing, weight bearing can be increased stepwise over another 4-week period up to full body weight. A full length orthotic is recommended for at least 12 months with heel cup and good medial support. RESULTS: The procedure allows correction of calcaneal deformities with preservation of soft tissue, normally as part of a hindfoot correction, e. g., in posterior tibial tendon insufficiency, varus deformities or total ankle replacement. In the literature and in our patients, the rate of injuries of the neurovascular bundle was not increased compared to open surgery. The average calcaneal shift was 1 cm, when necessary an additional correction was realized by rotation of the tuber calcanei. PMID- 27406043 TI - [The mini-open Latarjet procedure for treatment of recurrent anterior instability of the shoulder]. AB - OBJECTIVE: Shoulder stabilization. INDICATIONS: Symptomatic recurrent anterior shoulder instability combined with glenoid bone loss of approximately 20-35 % of the glenoid surface, engaging Hill-Sachs lesion and/or previously failed arthroscopic Bankart repair. In patients with a high risk of redislocation (contact sports) or irreparable soft tissue injury the Latarjet procedure can be considered as a first-line treatment. CONTRAINDICATIONS: Contraindicated if arthroscopic Bankart repair is possible. Irreparable damage of subscapularis tendon. Bony defect >35 % of the glenoid that cannot be filled with coracoid bone block. Arbitrary shoulder dislocation. Young patients with open growth plates (relative contraindication). SURGICAL TECHNIQUE: Mini-open deltopectoral approach of approximately 6 cm. Preparation of the coracoid process and the conjoined tendons. Osteotomy of the coracoid process at its base using a 90 degrees sawblade. Split of the subscapularis tendon. Preparation of the glenoid defect and implantation of 2-3 suture anchors where appropriate. Drilling of two parallel holes through the coracoid process. Fixation of the bone block with cannulated screws at the anterior glenoid rim and refixation of the joint capsula, if necessary with the help of the suture anchors. Wound drainage and closure in layers. POSTOPERATIVE MANAGEMENT: Intermittent immobilization in a sling for 6 weeks with limited abduction, flexion and external rotation. Sport specific training after 3 months, over-head sports after 6 months. RESULTS: Since 2009 64 mini-open Latarjet procedures (61 patients) performed. In all, 9.4 % of patients suffered from persistent instability (dislocations and subluxations); only 1 patient needed revision surgery due to instability. PMID- 27406044 TI - Immunobiological properties of influenza A (H7N9) hemagglutinin and neuraminidase proteins. AB - Recombinant vaccinia viruses harboring the complete hemagglutinin (HA) or neuraminidase (NA) genes from the influenza A/Anhui/1/2013 (H7N9) virus were constructed (rVac-H7 HA and rVac-N9 NA viruses). The HA and NA proteins were expressed in the cytoplasm and on the plasma membrane of thymidine-kinase negative (TK(-)) cells infected with these recombinant viruses. Only one form of the HA protein was expressed in infected TK(-) cells, with a molecular weight (MW) of 75 kDa, but three forms were found when the culture medium was supplemented with trypsin (MWs of 75, 50 and 27 kDa), which was similar to what was found in Madin-Darby canine kidney (MDCK) cells infected with reverse genetic (rg) influenza viruses carrying HA genes of H7N9 virus origin. One form of hyperglycosylated NA protein with a MW of 75 kDa was produced in rVac-N9-NA-virus infected TK(-) or MDCK cells. The MW decreased to 55 kDa after deglycosylation. The hyperglycosylated recombinant NA protein demonstrated sialidase activity in a fetuin-based neuraminidase assay. The rVac-H7 HA and rVac-N9 NA viruses elicited significantly higher anti-HA and anti-NA antibody titers in BALB/c mice that were immunized once than in ICR mice. The anti-HA and anti-NA antibodies showed activity against homosubtypic HA or NA, but not against heterosubtypic HA or NA, as determined by hemagglutination-inhibition and microneutralization assays for anti-HA antibodies and neuraminidase-inhibition and replication-inhibition assays for anti-NA antibodies. Taken together, our data demonstrated immunobiological properties of recombinant HA and NA proteins that might be useful for vaccine development. PMID- 27406045 TI - Therapeutic Challenges of Hepatic Mucormycosis in Hematologic Malignancy: A Case Report and Review of the Literature. AB - BACKGROUND The clinical presentation of mucormycosis can vary widely based on various host factors. Among malignancy- and bone marrow transplant-associated infections, the lungs are the most common site of infection. Involvement of the gastrointestinal tract is less frequently encountered. The clinical presentation is often nonspecific, and cultures typically yield no growth, making the diagnosis challenging. CASE REPORT We present a case of isolated hepatic mucormycosis in the setting of neutropenic fever and abdominal pain following induction chemotherapy for the treatment of acute myeloid leukemia. The patient was treated with combination antifungal therapy with amphotericin and posaconazole without surgical resection, given the presence of multiple liver lesions. After a prolonged course of dual antifungal therapy, the size of her liver lesions improved. Unfortunately, her lymphoproliferative disorder proved fatal, following approximately 13 months of antifungal therapy. CONCLUSIONS Among patients with mucormycosis, mortality remains high, especially in the setting of gastrointestinal involvement. Although surgical resection along with dual antifungal therapy can improve outcomes, the high mortality rate necessitates further investigation into improved diagnostic and treatment strategies including optimal antifungal therapy. PMID- 27406046 TI - Dual-Charged Hollow Fiber Membranes for Low-Pressure Nanofiltration Based on Polyelectrolyte Complexes: One-Step Fabrication with Tailored Functionalities. AB - A new nanofiltration (NF) hollow fiber membrane is developed by using two oppositely charged polyelectrolytes coagulating into a polyelectrolyte complex (PEC) onto polyether sulfone base polymer. The particular membrane architecture emerges during a single-step procedure, allowing setting both the porous negatively charged support of the hollow fiber and the separation layer containing also the positive polyelectrolyte (PEI/PDADMAC) through a single layer dry-jet wet spinning process. The novelty is two-pronged: the composition of the hollow fiber membrane itself and its fabrication procedure (one-step fabrication of membranes employing polyelectrolytes). These result in highly permeable hollow fiber membranes with a stable separation layer and performance at par with the membranes reported in literature obtained by multistep processes. More importantly, the membranes are obtained through a simple, very fast (one-step), and less expensive procedure. The best performance among these newly obtained hollow-fiber membranes is achieved by PD5% hollow fiber (MWCO of 300 Da), which showed 7.6 L/m(2).h.bar permeability and ~90% rejection of MgCl2, MgSO4, and Na2SO4 at 2 bar pressure. Thus, the resulting membranes not only have the advantages of the hollow-fiber configuration, but perform very well at extremely low pressures (the lowest reported in the literature). The broad impact of the results presented in this Article lies in the potential to dramatically reduce both the fabrication (duration and complexity) and the price and desalination costs of highly performing NF hollow fiber membranes. These might result in interesting potential applications and open new directions toward designing efficient functional NF hollow fibers for water desalination. PMID- 27406047 TI - More doctors are engaged in commissioning under CCGs. PMID- 27406048 TI - A circular challenge. PMID- 27406049 TI - Eco-friendly nitrogen-containing carbon encapsulated LiMn2O4 cathodes to enhance the electrochemical properties in rechargeable Li-ion batteries. AB - This study describes the synthesis of nitrogen-containing carbon (N-C) and an approach to apply the N-C material as a surface encapsulant of LiMn2O4 (LMO) cathode material. The N heteroatoms in the N-C material improve the electrochemical performance of LMO. A low-cost wet coating method was used to prepare N-C@LMO particles. The N-C@LMO was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), high-resolution Raman spectroscopy (HR-Raman), field emission scanning electron microscopy (FE-SEM), and field emission scanning transmission electron microscopy (FE-TEM) with elemental mapping. Furthermore, the prepared samples were electrochemically studied using the AC electrochemical impedance spectroscopy (EIS) and the electrochemical cycler. XPS suggested that the N-C coating greatly reduced the dissolution of Mn and EIS showed that the coating greatly suppressed the charge transfer resistance, even after long-term cycling. The control of Mn dissolution and inner resistance allowed faster Li-ion transport between the two electrodes resulting in improved discharge capacity and cycling stability. PMID- 27406050 TI - Evaluation of the Metasin assay for intraoperative assessment of sentinel lymph node metastases in breast cancer. AB - AIMS: Sentinel lymph node (SLN) biopsy is the preferred surgical technique for staging the axilla in clinically node-negative breast cancer. Accurate intraoperative staging allows for the immediate performance of an axillary clearance in node-positive patients. We assessed the Metasin assay for the intraoperative analysis of SLNs in a prospective evaluation of 250 consecutive patients undergoing intraoperative SLN analysis at the Breast Unit, University Hospital, Southampton, UK. METHODS: Metasin uses a quantitative reverse transcription PCR to detect two markers of metastasis: cytokeratin 19 (CK19) an epithelial marker and mammaglobin (MGB) a breast specific marker. Metasin results were compared with the results from routine paraffin block histopathology. RESULTS: Metasin was robust, with a failure rate of <1%, and demonstrated excellent accuracy and reproducibility. The average turnaround time for the Metasin assay was 42 min, the largest variable being the number of nodes assayed. A total of 533 SLNs were evaluated with 75 patients testing positive for MGB and/or CK19. Based on the analysis of individual SLNs, the overall concordance between Metasin and histology was 92.3% (sensitivity 88.7%, specificity 92.9%). When adjusted for tissue allocation bias, the concordance was 93.8% (sensitivity 89.8%, specificity 94.6%). In this evaluation, 57/250 patients (23%) proceeded to axillary clearance based on Metasin results and were considered spared a second operative procedure. CONCLUSIONS: Metasin has proven to be an accurate, reproducible and reliable laboratory test. The analysis time is acceptable for intraoperative use, and in comparison to routine histology demonstrates acceptable concordance, sensitivity and specificity. PMID- 27406051 TI - Review of the national external quality assessment (EQA) scheme for breast pathology in the UK. AB - BACKGROUND: The National Health Service Breast Screening Programme (NHSBSP; pathology) external quality assurance (EQA) scheme aims to provide a mechanism for examination and monitoring of concordance of pathology reporting within the UK. This study aims to review the breast EQA scheme performance data collected over a 24-year period following its introduction. METHODS: Data on circulations, number of cases and diagnosis were collected. Detailed analyses with and without combinations of certain diagnostic entities, and over different time periods were performed. RESULTS: Overall, of 576 cases (172 benign, 11 atypical hyperplasia, 98 ductal carcinoma in situ/microinvasive and 295 invasive disease), consistency of assessment of diagnostic parameters was very high (overall k=0.80; k for benign diagnosis=0.79; k for invasive disease=0.91). For distinguishing benign versus malignant lesions, no further improvement is considered possible in view of the limitations of the scheme methodology. Although diagnostic consistency of atypical hyperplasia remains at a low level, combining it with the benign category results in a high level of agreement (k=0.93). The level of consistency of reporting prognostic information is variable and some items such as lymphovascular invasion and tumour size measurement may need further intervention to improve their reporting consistency. Although the level of consistency of reporting of histological grade remained at a moderate level overall (k=0.48), it was variable among cases and appears to have levelled off; no further significant improvement is expected and no significant impact of the previous publication of guidelines is observed. CONCLUSIONS: These results provide further evidence to indicate the value of the breast EQA scheme in monitoring performance and the identification of specific areas where improvement or new approaches are required. For most parameters, the concordance of reporting reached a plateaux a few years after the introduction of the EQA scheme. It is important to maintain this high level and also to tackle specific low-performance areas innovatively. PMID- 27406052 TI - beta-Catenin activation in fundic gland polyps, gastric cancer and colonic polyps in families afflicted by 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS). AB - AIM: To evaluate possible colon involvement in the 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS) gastrointestinal polyposis syndrome. METHODS: Prospective clinicopathological evaluation of two GAPPS families and expression of nuclear beta-catenin, p53 and Ki67 measured by immunohistochemistry on endoscopic and surgical specimens from patients with GAPPS. RESULTS: Patients with the GAPPS phenotype were more frequently affected by colonic polyps than patients at risk within the same families (p<0.01). Colonic polyps shared immunohistochemical features of fundic gland polyps and gastric cancers including increased expression of nuclear beta-catenin, Ki67 and p53. Both gastric and colonic lesions harboured activating somatic variants of beta-catenin signalling. CONCLUSIONS: Similarities in expression markers in fundic gland and colonic polyps, together with an enrichment of colonic adenomas in family members affected by GAPPS phenotype compared with family members at risk, support mild colonic involvement of this rare cancer syndrome. Colonoscopic screening might be warranted. CLINICAL TRIAL REGISTRATION NUMBER: #09-C-0079; Results. PMID- 27406054 TI - [Jinn possession as an explanation of mental illness influences the treatment seeking behaviour]. AB - Jinn possession is used as an explanation of mental symptoms among Muslims around the world. Very few studies have examined the use of jinn as a religious explanation model for mental health problems and treatment-seeking behaviour. The majority of studies show a positive association between jinn explanations and preferred treatment by religious healers, but due to methodological limitations, results should be taken with precaution. There is a need for longitudinal studies focusing on improving cultural competence and exploring possible cooperation with healers. PMID- 27406055 TI - [Bickerstaff brainstem encephalitis after upper respiratory infection]. AB - Bickerstaff brainstem encephalitis (BE) is a very rare neurological condition with subacute onset of ophthalmoplegia, ataxia and altered sensorium, often postinfectious. The condition is associated with the anti-GQ1b antibody syndrome and is part of the spectrum of diseases including Miller Fisher syndrome and Guillain-Barre syndrome. In this case, we report the history, workup, treatment and follow-up of a 48-year-old woman with probable BE without anti-GQ1b antibodies in relation to the international diagnostic criteria. PMID- 27406053 TI - Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of Tau protein. AB - The mechanistic relationship between amyloid beta1-42 (Abeta1-42) and the alteration of Tau protein are debated. We investigated the effect of Abeta1-42 monomers and oligomers on Tau, using mice expressing wild-type human Tau that do not spontaneously develop Tau pathology. After intraventricular injection of Abeta1-42, mice were sacrificed after 3 h or 4 days. The short-lasting treatment with Abeta monomers, but not oligomers, showed a conformational PHF-like change of Tau, together with hyperphosphorylation. The same treatment induced increase in concentration of GSK3 and MAP kinases. The inhibition of the kinases rescued the Tau changes. Abeta monomers increased the levels of total Tau, through the inhibition of proteasomal degradation. Abeta oligomers reproduced all the aforementioned alterations only after 4 days of treatment. It is known that Abeta1-42 monomers foster synaptic activity. Our results suggest that Abeta monomers physiologically favor Tau activity and dendritic sprouting, whereas their excess causes Tau pathology. Moreover, our study indicates that anti-Abeta therapies should be targeted to Abeta1-42 monomers too. PMID- 27406056 TI - [Lifestyle interventions affect the surgical outcome]. AB - Observational studies have shown that poor nutritional status or obesity, smoking, alcohol drinking/abuse, and physical fitness are associated to a variety of poor surgical outcomes. Interventional studies show some effect of preoperative smoking cessation, alcohol abstinence, perioperative alcohol intervention, and exercise on wound healing and infectious outcomes. Patients scheduled for benign surgery should be encouraged to smoking cessation and alcohol abstinence. Evidence on other lifestyle interventions, vulnerable patients and acute surgical settings is still lacking. PMID- 27406057 TI - [Kronisk hofteluksation som folge af ubehandlet hoftedysplasi]. PMID- 27406058 TI - Effect of chitosan on the formation of acrylamide and hydroxymethylfurfural in model, biscuit and crust systems. AB - Chitosan has been popular as a natural food preservative due to its antibacterial and antifungal activities. It may be used in thermally processed foods such as bread to delay staling and improve the microbial stability during the shelf-life. However, the thermal process could lead to the formation of harmful compounds in bakery products through chemical reactions, in which chitosan could take part. Therefore, this study aims to investigate the effect of chitosan on the formation of acrylamide and hydroxymethylfurfural (HMF) in different model systems. Addition of acid to the asparagine-glucose model system decreased the initial rate of acrylamide formation to approx. 4-times. The chitosan included model system contained higher acrylamide than the asparagine-glucose-acid model but still lower than the asparagine-glucose model system. The HMF content was decreased in the presence of acid due to acid-catalyzed degradation. Additionally, HMF is a potent carbonyl source and utilized in the Maillard reaction. In biscuit samples, addition of acid or chitosan solution to the dough did not significantly affect the acrylamide formation (p > 0.05), however addition of acid increased the formed HMF. In crust samples, acrylamide formation was decreased by acid, while chitosan showed no additional decrease. No interaction was found between HMF and chitosan. The results suggest that the effect of chitosan should be carefully evaluated apart from the effect of acid, in which chitosan was solubilized. PMID- 27406059 TI - Reference gene selection and RNA preservation protocol in the cat flea, Ctenocephalides felis, for gene expression studies. AB - The cat flea, Ctenocephalides felis, is a major pest species on companion animals thus of significant importance to the animal health industry. The aim of this study was to develop sampling and storage protocols and identify stable reference genes for gene expression studies to fully utilize the growing body of molecular knowledge of C. felis. RNA integrity was assessed in adult and larvae samples, which were either pierced or not pierced and stored in RNAlater at ambient temperature. RNA quality was maintained best in pierced samples, with negligible degradation evident after 10 days. RNA quality from non-pierced samples was poor within 3 days. Ten candidate reference genes were evaluated for their stability across four group comparisons (developmental stages, genders, feeding statuses and insecticide-treatment statuses). Glyceraldehyde 3 phosphate dehydrogenase (GAPDH), 60S ribosomal protein L19 (RPL19) and elongation factor-1alpha (Ef) were ranked highly in all stability comparisons, thus are recommended as reference genes under similar conditions. Employing just two of these three stable reference genes was sufficient for accurate normalization. Our results make a significant contribution to the future of gene expression studies in C. felis, describing validated sample preparation procedures and reference genes for use in this common pest. PMID- 27406060 TI - Antioxidant N-Acetylcysteine and Glutathione Increase the Viability and Proliferation of MG63 Cells Encapsulated in the Gelatin Methacrylate/VA-086/Blue Light Hydrogel System. AB - Photoencapsulation of cells inside a hydrogel system can provide a suitable path to establish a gel in situ for soft tissue regeneration applications. However, the presence of photoinitiators and blue or UV light irradiation can result in cell damage and an increase of reactive oxygen species. We here evaluate the benefits of an antioxidant pretreatment on the photoencapsulated cells. We study this by evaluating proliferation and viability of MG63 cells, which we combined with a gelatin methacrylate (GelMA) hydrogel system, using the photoinitiator, VA 086, cured with 440 nm blue light. We found that blue light irradiation as well as the presence of 1% VA-086 reduced MG63 cell proliferation rates. Adding a short pretreatment step to the MG63 cells, consisting of the antioxidant molecules N-acetylcysteine (NAC) and reduced glutathione (GSH), and optimizing the GelMA encapsulation steps, we found that both NAC and GSH pretreatments of MG63 cells significantly increased both proliferation and viability of the cells, when using a 15% GelMA hydrogel, 1% VA-086, and 1-min blue light exposure. These findings suggest that the use of antioxidant pretreatment can counteract the negative presence of the photoinitiators and blue light exposure and result in a suitable environment for photoencapsulating cells in situ for tissue engineering and soft tissue applications. PMID- 27406061 TI - Three-Dimensional Face Recognition in Mild Cognitive Impairment: A Psychophysical and Structural MR Study. AB - OBJECTIVES: Mild cognitive impairment (MCI) has been associated with a high risk of conversion to Alzheimer's dementia. In addition to memory complaints, impairments in the visuospatial domain have been reported in this condition. We have previously shown that deficits in perceiving structure-from-motion (SFM) objects are reflected in functional reorganization of brain activity within the visual ventral stream. Here we aimed to identify structural correlates of psychophysical complex face and object recognition performance in amnestic MCI patients (n=30 vs. n=25 controls). This study was, therefore, motivated by evidence from recent studies showing that a combination of visual information across dorsal and ventral visual streams may be needed for the perception of three-dimensional (3D) SFM objects. METHODS: In our experimental paradigm, participants had to discriminate 3D SFM shapes (faces and objects) from 3D SFM meaningless (scrambled) shapes. RESULTS: Morphometric analysis established neuroanatomical evidence for impairment in MCI as demonstrated by smaller hippocampal volumes. We found association between cortical thickness and face recognition performance, comprising the occipital lobe and visual ventral stream fusiform regions (overlapping the known location of face fusiform area) in the right hemisphere, in MCI. CONCLUSIONS: We conclude that impairment of 3D visual integration exists at the MCI stage involving also the visual ventral stream and contributing to face recognition deficits. The specificity of such observed structure-function correlation for faces suggests a special role of this processing pathway in health and disease. (JINS, 2016, 22, 744-754). PMID- 27406062 TI - High-frequency versus low-frequency microwave ablation in malignant liver tumours: evaluation of local tumour control and survival. AB - PURPOSE: To compare local tumour control and survival rates in patients with liver metastases treated with microwave ablation (MWA), using either a low frequency (LF) (915 MHz) or high-frequency (HF) system (2.45 GHz). MATERIALS AND METHODS: The retrospective study included 221 patients (mean age: 61.7 years) with 356 malignant hepatic lesions. Ninety-four patients with 133 lesions underwent LF-MWA between September 2008 and February 2011, while 127 patients with 223 lesions were treated with HF-MWA between March 2011 and July 2013. MRI was performed after 24 h from each procedure and at 3, 6, 9, 12, 18 and 24 months post-ablation. Both groups were compared with the Fisher's exact test. Survival rates were calculated using the Kaplan-Meier test. RESULTS: The mean initial ablation volume of LF-MWA was nearly half of HF-MWA (19.1 mL vs. 39.9 mL). The difference in volume between both systems was significant (p < .0001). With LF MWA, 39/133 lesions (29.32%) progressed at follow-up while the number of lesions which progressed with HF-MWA was 10/223 (4.5%). The mean time to progression was 5.03 and 5.31 months for the lesions treated with LF-MWA and HF-MWA, respectively. The difference between both systems was significant (p = .00059). The 1-, 2- and 4-year overall survival rates for curative indication were 98.9%, 95.7% and 82.9% for LF-MWA, respectively, and were 100%, 97.6% and 92.9% for HF MWA, respectively. The difference in survival rates was not significant (p > .05). CONCLUSION: Both LF- and HF-MWA systems are effective treatment options for oligonodular liver malignant lesions, but significantly higher ablation volumes, longer time to progression and lower progression rates were observed in HF-MWA. PMID- 27406063 TI - Cluster randomized trial assessing the effects of rapid ethical assessment on informed consent comprehension in a low-resource setting. AB - BACKGROUND: Maximizing comprehension is a major challenge for informed consent processes in low-literacy and resource-limited settings. Application of rapid qualitative assessments to improve the informed consent process is increasingly considered useful. This study assessed the effects of Rapid Ethical Assessment (REA) on comprehension, retention and quality of the informed consent process. METHODS: A cluster randomized trial was conducted among participants of HPV sero prevalence study in two districts of Northern Ethiopia, in 2013. A total of 300 study participants, 150 in the intervention and 150 in the control group, were included in the study. For the intervention group, the informed consent process was designed with further revisions based on REA findings. Informed consent comprehension levels and quality of the consent process were measured using the Modular Informed Consent Comprehension Assessment (MICCA) and Quality of Informed Consent (QuIC) process assessment tools, respectively. RESULT: Study recruitment rates were 88.7 % and 80.7 % (p = 0.05), while study retention rates were 85.7 % and 70.3 % (p < 0.005) for the intervention and control groups respectively. Overall, the mean informed consent comprehension scores for the intervention and control groups were 73.1 % and 45.2 %, respectively, with a mean difference in comprehension score of 27.9 % (95 % CI 24.0 % - 33.4 %; p < 0.001,). Mean scores for quality of informed consent for the intervention and control groups were 89.1 % and 78.5 %, respectively, with a mean difference of 10.5 % (95 % CI 6.8 -14.2 %; p < 0.001). CONCLUSION: Levels of informed consent comprehension, quality of the consent process, study recruitment and retention rates were significantly improved in the intervention group. We recommend REA as a potential modality to improve informed consent comprehension and quality of informed consent process in low resource settings. PMID- 27406065 TI - Sex, Race, and Age Disparities in the Improvement of Survival for Gastrointestinal Cancer over Time. AB - There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66 0.83), 0.49 (95% CI, 0.37-0.64), 0.69 (95% CI, 0.65-0.76), 0.62 (95% CI, 0.54 0.69), and 0.56 (95% CI, 0.42-0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists. PMID- 27406066 TI - Unravelling the optical responses of nanoplasmonic mirror-on-mirror metamaterials. AB - Mirror-on-mirror platforms based on arrays of metallic nanoparticles, arranged top-down or self-assembled on a thin metallic film, have interesting optical properties. Interaction of localized surface-plasmons in nanoparticles with propagating surface-plasmons in the film underpins the exotic features of such platforms. Here, we present a comprehensive theoretical framework which emulates such a system using a five-layer-stack model and calculate its reflectance, transmittance, and absorbance spectra. The theory rests on dipolar quasi-static approximations incorporating image-forces and effective medium theory. Systematically tested against full-wave simulations, this simple approach proves to be adequate within its obvious applicability limits. It is used to study optical signals as a function of nanoparticle dimensions, interparticle separation, metal film thickness, the gap between the film and nanoparticles, and incident light characteristics. Several peculiar features are found, e.g., quenching of reflectivity in certain frequency domains or shift of the reflectivity spectra. Schemes are proposed to tailor those as functions of the mentioned parameters. Calculating the system's optical responses in seconds, as compared to much longer running simulations, this theory helps to momentarily unravel the role of each system parameter in light reflection, transmission, and absorption, facilitating thereby the design and optimisation of novel mirror-on mirror systems. PMID- 27406064 TI - Transcriptional profiling reveals intrinsic mRNA alterations in multipotent mesenchymal stromal cells isolated from bone marrow of newly-diagnosed type 1 diabetes patients. AB - BACKGROUND: Bone marrow multipotent mesenchymal stromal cells (MSCs) are a diverse subset of precursors that contribute to the homeostasis of the hematopoietic niche. MSCs can be isolated and expanded in vitro and have unique immunomodulatory and regenerative properties that make them attractive for the treatment of autoimmune diseases, including type 1 diabetes (T1D). Whether autologous or allogeneic MSCs are more suitable for therapeutic purposes has not yet been established. While autologous MSCs may present abnormal function, allogeneic cells may be recognized and rejected by the host immune system. Thus, studies that investigate biological characteristics of MSCs isolated from T1D patients are essential to guide future clinical applications. METHODS: Bone marrow-derived MSCs from recently diagnosed type 1 diabetes patients (T1D-MSCs) were compared with those from healthy individuals (C-MSCs) for morphological and immunophenotypic characteristics and for differentiation potential. Bioinformatics approaches allowed us to match absolute and differential gene expression of several adhesion molecules, immune mediators, growth factors, and their receptors involved with hematopoietic support and immunomodulatory properties of MSCs. Finally, the differentially expressed genes were collated for functional pathway enrichment analysis. RESULTS: T1D-MSCs and C-MSCs were similar for morphology, immunophenotype, and differentiation potential. Our absolute gene expression results supported previous literature reports, while also detecting new potential molecules related to bone marrow-derived MSC functions. T1D-MSCs showed intrinsic abnormalities in mRNA expression, including the immunomodulatory molecules VCAM-1, CXCL12, HGF, and CCL2. Pathway analyses revealed activation of sympathetic nervous system and JAK STAT signaling in T1D-MSCs. CONCLUSIONS: Collectively, our results indicate that MSCs isolated from T1D patients present intrinsic transcriptional alterations that may affect their therapeutic potential. However, the implications of these abnormalities in T1D development as well as in the therapeutic efficacy of autologous MSCs require further investigation. PMID- 27406067 TI - A highly efficient noble metal free photocatalytic hydrogen evolution system containing MoP and CdS quantum dots. AB - We report the construction of a highly efficient noble metal free photocatalytic hydrogen (H2) evolution system using CdS quantum dots as the light absorber and metallic MoP as the cocatalyst. MoP can be prepared by a facile temperature programmed reduction method and small clusters of MoP nanoparticles sized 10-30 nm were obtained by probe ultrasonication. The effect of synthesis conditions on the electrocatalytic and photocatalytic H2 evolution activity of MoP was investigated. The highest H2 evolution rate of 1100 MUmol h(-1) can be achieved by the optimized system under visible light (lambda>= 420 nm), which is comparable to that when Pt was used as the cocatalyst. A high quantum efficiency of 45% is obtained at 460 nm irradiation. PMID- 27406068 TI - Phytochemical and biological investigations of Amaryllidaceae alkaloids: a review. AB - Amaryllidaceae is a family that includes 75 genera and about 1100 species, which have a long history of medicinal use. Many plants have been proven to possess efficacy for neurological injury and inflammatory conditions. This article summarizes 357 Amaryllidaceae alkaloids, and cites 166 174 references over the last three decades. These alkaloids are classified into 14 skeleton types, and their abundant sources are also included. Modern pharmacology studies demonstrate that alkaloids that exclusively occur in Amaryllidaceae plant possess wide ranging pharmacological actions, especially effects on the central nervous system, as well as antitumor, antimicrobial, and anti-inflammatory activities. Effective monomeric compounds from Amaryllidaceae screened for pharmacological activity in vivo and in vitro are also summarized. PMID- 27406069 TI - European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology. AB - BACKGROUND: The treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe clinical cases, the use of immunoglobulin is not generally based on data from randomized controlled trials that are usually required for the practice of evidence-based medicine. Owing to the rarity of the indications for the use of IVIg, it is also unlikely that such studies will be available in the foreseeable future. Because the high costs of IVIg treatment also limit its first-line use, the first clinical guidelines on its use in dermatological conditions were established in 2008 and renewed in 2011. MATERIALS AND METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the EDF and the EADV. The guidelines were developed to update the indications for treatment currently considered as effective and to summarize the evidence base for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases. PMID- 27406071 TI - The fate of the free radical. PMID- 27406070 TI - Uncertainty analysis for an effluent trading system in a typical nonpoint-sources polluted watershed. AB - Conventional effluent trading systems (ETSs) between point sources (PSs) and nonpoint sources (NPSs) are often unreliable because of the uncertain characteristics of NPSs. In this study, a new framework was established for PS NPS ETSs, and a comprehensive analysis was conducted by quantifying the impacts of the uncertainties associated with the water assimilative capacity (WAC), NPS emissions, and measurement effectiveness. On the basis of these results, the uncertain characteristics of NPSs would result in a less cost-effective PS-NPS ETS during most hydrological periods, and there exists a clear transition occurs from the WAC constraint to the water quality constraint if these stochastic factors are considered. Specifically, the emission uncertainty had a greater impact on PSs, but an increase in the emission or abatement uncertainty caused the abatement efforts to shift from NPSs toward PSs. Moreover, the error transitivity from the WAC to conventional ETS approaches is more obvious than that to the WEFZ-based ETS. When NPSs emissions are relatively high, structural BMPs should be considered for trading, and vice versa. These results are critical to understand the impacts of uncertainty on the functionality of PS-NPS ETSs and to provide a trade-off between the confidence level and abatement efforts. PMID- 27406072 TI - Spectrophotometric determination of antioxidant activity. AB - The spectrophotometric technique for total antioxidant activity (TAA)(1,2) measures the relative abilities of antioxidants to scavenge the 2,2'-azino-bis(3 ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical cation (ABTS(*+)) in comparison with the antioxidant potency of standard amounts of Trolox, the water soluble vitamin E analogue. This method is based on the progressive consumption of antioxidant activity by ABTS(*+) as it is generated in the reaction cuvette and can be automated with a spectrophotometric analyzer. Several different analytical strategies are possible using the same reagents, enabling the assay system to be used to determine the antioxidant activity of plasma, saliva, lipoprotein fractions, foods and beverages. To determine the activity of pure antioxidant substances, a hydrogen peroxide concentration of 75 MUM is used, together with a 6 min measuring time. For biological samples with endogenous peroxidase activity the hydrogen peroxide concentration is increased fivefold and the measuring time shortened to 3.25 min. Assays with improved sensitivity are described for low-density lipoprotein (LDL) preparations and saliva. Use of a spectrophotometric endpoint makes the assay simple to carry out without special laboratory equipment. Measurement at 734 nm avoids a range of potential interfering factors, such as sample turbidity and non-specific absorbance by sample constituents. Current applications of the ABTS antioxidant assay are described and discussed. PMID- 27406073 TI - Reaction of peroxynitrite with L-tryptophan. AB - The reaction between peroxynitrous acid (hydrogen oxoperoxonitrate) and L tryptophan is 130 M(-1)s(-1) at 25 degrees C. The pH dependence of the second order rate constant shows a maximum at pH 5.1. The enthalpy and entropy of activation at pH 7.1 are 10.6 +/- 0.4 kcal.mol(-1) and -16 +/- 2 cal.mol(-1)K(-1) respectively. High-performance liquid chromatography analysis revealed a number of reaction products, two of which were identified as 5- and 6- nitrotryptophan. Hydroxytryptophans were not observed, even at low peroxynitrite concentrations where most of the peroxynitrite decays to nitrate via a first-order process. These results support the hypothesis that isomerization of protonated peroxynitrite to nitrate does not involve formation of the hydroxyl radical. PMID- 27406074 TI - Melatonin and structurally-related, endogenous indoles act as potent electron donors and radical scavengers in vitro. AB - The radical scavenging properties of melatonin, structurally-related indoles and known antioxidants were investigated in kinetic competition studies using the specific radical trapping reagent 2,2'-azino-bis(3-ethylbenz-thiazoline-6 sulfonic acid) (ABTS). In the presence of highly reactive radicals, ABTS is oxidized to the stable thiazoline cation radical, ABTS*(+) which, due to its intense green color, can be measured photometrically at 420 nm absorbance. The indoles melatonin, 5-methoxytryptophol, 5-methoxyindole acetic acid and 5 methoxytryptamine as well as the phenolic and thiolic antioxidants ascorbic acid, Trolox, and glutathione inhibited ABTS cation radical formation and catalyzed ABTS radical cation reduction. Melatonin was the most potent radical scavenger and electron donor when compared with the methoxylated indole analogs and the other antioxidants tested. Melatonin, the methoxylated indole analogs and the other antioxidants tested acted as potent electron donors which scavenged initiating and propagating radicals and repaired oxidative damage due to electrophile intermediates. PMID- 27406075 TI - Facile reaction of gangliosides with hydroxyl radical. AB - The reactivity of gangliosides with superoxide anion (O2(*-)) and hydroxyl radical (HO(*)) was evaluated by ESR spin-trapping using 5,5-dimethyl-1-pyrroline N-oxide under physiological conditions (1/15 M phosphate buffer, pH 7.4). Gangliosides proved to react with HO(*) but not with O2(*-). The second order rate constants for various gangliosides with HO(*) ranged from 5 * 10(9) M(-1)s( 1) to 16 * 10(9) M(-1)s(-1). The rate constant for tetrasialoganglioside, GQ1b, was about three times higher than that of monosialoganglioside, GM1. The reactivity of gangliosides and asialo-GM1 with HO(*) was in the order: GQ1b >GT1b >GD1a >GD1b = GM1 ? asialo-GM1. The observed high reactivity of gangliosides probably involves the sialyl residues, since sialic acid was shown to be more reactive with HO(*) than d-glucose under the same conditions. PMID- 27406076 TI - Copper chelation by tryptophan inhibits the copper-ascorbate oxidation of tryptophan. AB - The in vitro oxidation of tryptophan (Trp) by pro-oxidant systems such as iron ascorbate indicates that Trp is a target for oxygen radicals in vivo. The Trp in albumin and lipoproteins has been reported to be actively oxidized by hydroxyl radical (HO(*)) generating systems such as copper-ascorbate or PUFA (polyunsaturated fatty acids) respectively. The super-physiological concentrations of the oxidants used in these studies prompted us to examine the effect of low copper and ascorbate concentrations on Trp oxidation. Trp (10-5000 MUmol/L) was incubated with 1.5 MUmol/L copper plus ascorbate (0.113 and 1.13 mmol/L) at 37 degrees C and its oxidation followed by fluorescence and high performance liquid chromatography. The percentage of Trp oxidized by the ascorbate-copper system was inversely related to its concentration and positively related to the ascorbate concentration. High concentrations of Trp (above 50 MUmol/L for 0.113 mmol/L and 500 MUmol/L for 1.13 mmol/L ascorbate) are not significantly oxidized in the presence of ascorbate. The large drop in the percentage Trp oxidation at higher concentrations may be due to the chelation of copper by Trp. High concentrations of Trp (over 50 MUmol/L) strongly prevented ascorbate oxidation by copper, and therefore inhibited the production of HO(*) needed for Trp oxidation. Protein Trp is less readily oxidized by the ascorbate copper system than free Trp. Proteins chelate copper much better than Trp, and so inhibit its oxidative activity, at least against ascorbic acid. PMID- 27406077 TI - Maternal cadmium intoxication: effects on fetal brain antioxidant defense parameters. AB - The antioxidant potential of the brain in developing fetuses was assessed at gestational days (GD) 16, 18 and 20 and postnatal day (PND)1. Higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were noticed during fetal development which were reduced to about half and one-quarter, respectively, at PND 1. Glutathione reductase (GR) activity remained stationary throughout the experiment and the values were very high compared to those reported for weanling rats. In contrast, catalase (CAT) activity increased with development. Glutathione (GSH) and total sulfhydryls (TSH) were maximum in 16-day fetal brains and declined subsequently. Brain lipid peroxidation (LPO) was found to increase with age. A group of animals was exposed to 20 ppm cadmium (Cd) in drinking water from the day of conception up to PND 1. Cd was found to increase the activities of brain SOD, CAT, and GR significantly at all the time intervals. The metal exposure decreased fetal brain GPx at GD 18 and 20, whereas GPx activity declined precipitously in both groups on PND 1. Cd caused both increments and decrements in the GSH and TSH levels (depending on gestational day) and increased the LPO in brain. It may be concluded that the Cd-intoxicated fetal brain undergoes significant changes in antioxidant defense parameters which, overall, may be sufficient to permit near-normal development and prevent substantial oxidant damage. PMID- 27406078 TI - Thiol-induced hemoglobin oxidation. AB - Addition of cysteine in the mM range to purified oxyhemoglobin, red blood cell lysate or red blood cell suspensions leads to oxidation of the hemoprotein. The rate and extent of the process depend on the initial hemoglobin and cysteine concentrations, and the reaction is limited by the total destruction of the sulfhydryl groups. Similar results are obtained employing glutathione, but the rate of the process is considerably slower. Oxidation of the purified hemoprotein is faster than in the red blood cell lysate. This difference is mainly due to the inhibitory effect of catalase present in the lysate. Addition of sodium azide increases the rate of oxyhemoglobin oxidation in the lysate, while addition of catalase reduces the rate of oxidation of the purified hemoprotein. The results are interpreted in terms of a mechanism comprising the oxidation of the oxyhemoglobin by the -SH group, with concomitant formation of superoxide anion and hydrogen peroxide. These species further contribute to the oxyhemoglobin oxidation. A chain oxidation of the thiol, catalyzed by the hemoprotein, explains the extensive cysteine destruction. PMID- 27406079 TI - Correspondence. PMID- 27406080 TI - Severity of coronary artery disease is an independent risk factor for decline in kidney function. AB - BACKGROUND AND AIM: Chronic kidney disease (CKD) and cardiovascular disease are closely interrelated and the presence of one condition synergistically affects the prognosis of the other, in a negative manner. There are surprisingly very few data on the relationship between baseline coronary artery disease (CAD) severity and subsequent decline in kidney function. We aimed to evaluate for the first time whether baseline coronary artery lesion severity predicts the decline in kidney function. MATERIALS AND METHODS: The study population was derived from a series of consecutive patients presenting with stable angina pectoris or angina equivalents, who underwent coronary angiography. SYNTAX score for each patient was calculated to define severity of CAD. Change in kidney function was defined by calculating the rates of change in eGFR. RESULTS: Among the 823 patients included in our study, the mean age was 59.2+/-10.7years, 78.4% were males, and 32% had diabetes. The mean baseline eGFR was 87.3+/-24.9ml/min/1.73m(2) and the median Syntax score was 14 (IQR=10-20). The median length of follow-up was 2.75years (IQR=2.42-3.50). The mean yearly change for eGFR in the entire study population was 4.06 (95% CI: 3.59-4.51)ml/min/1.73m(2). A higher Syntax score was associated with a significantly faster decline in eGFR in all (unadjusted and adjusted) models. During the follow-up, 103 patients developed CKD. A higher Syntax score, analyzed both as continuous and categorical variable, was associated with incident CKD in all models. CONCLUSION: We have demonstrated for the first time that severity of CAD is an independent risk factor for the decline in kidney function. Studies are needed to highlight the potential mechanisms regarding the association between severity of CAD and decline in kidney function. PMID- 27406081 TI - Dissection of genetic architecture of rice plant height and heading date by multiple-strategy-based association studies. AB - Xieyou9308 is a certified super hybrid rice cultivar with a high grain yield. To investigate its underlying genetic basis of high yield potential, a recombinant inbred line (RIL) population derived from the cross between the maintainer line XieqingzaoB (XQZB) and the restorer line Zhonghui9308 (ZH9308) was constructed for identification of quantitative trait SNPs (QTSs) associated with two important agronomic traits, plant height (PH) and heading date (HD). By re sequencing of 138 recombinant inbred lines (RILs), a total of ~0.7 million SNPs were identified for the association studies on the PH and HD. Three association mapping strategies (including hypothesis-free genome-wide association and its two complementary hypothesis-engaged ones, QTL-based association and gene-based association) were adopted for data analysis. Using a saturated mixed linear model including epistasis and environmental interaction, we identified a total of 31 QTSs associated with either the PH or the HD. The total estimated heritability across three analyses ranged from 37.22% to 45.63% and from 37.53% to 55.96% for the PH and HD, respectively. In this study we examined the feasibility of association studies in an experimental population (RIL) and identified several common loci through multiple strategies which could be preferred candidates for further research. PMID- 27406083 TI - Obeticholic Acid: First Global Approval. AB - Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. The drug is in preregistration for this indication in the EU. This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis. PMID- 27406082 TI - A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5*-familial Alzheimer's disease mice. AB - Deposition of amyloid beta protein (Abeta) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Abeta, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Abeta plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Abeta plaques in brain tissues from the 5*-familial AD (5*FAD) mice than the classical Abeta-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5*FAD mice. We observed that Cur and NC labeled Abeta plaques to the same degree as Abeta-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Abeta plaques in 5*FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Abeta plaques in 5*FAD brain tissue. Cur and NC also labeled different types of Abeta plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Abeta-specific antibody for labeling and imaging of Abeta plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Abeta-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy. PMID- 27406084 TI - Intolerance of uncertainty and insula activation during uncertain reward. AB - Individuals with high intolerance of uncertainty (IU) have been shown to exhibit abnormal threat responding, which may be mediated by hyperactive anterior insula (aINS) response to uncertainty. Research has indicated that individuals with high IU also exhibit abnormal positive valence responding, suggesting that IU may impact responding to uncertainty regardless of the valence of the potential outcome. To date, no study has investigated the neural processes associated with IU and response to uncertain positive stimuli, such as rewards. Therefore, this study was designed to examine the association between individual differences in IU and neural activation during uncertain reward using functional magnetic resonance imaging (fMRI). Thirty-seven adults completed a self-report measure of IU and a reward task during fMRI. Consistent with the threat literature, greater IU was associated with increased aINS activation during uncertain reward. This association was more robust for the prospective IU subscale, a dimension characterized by worry about future events. Together with prior studies, these findings provide evidence that IU is related to abnormal threat and reward responding, and that these deficits may be similarly linked to hyperactive aINS response to uncertainty. PMID- 27406085 TI - P300 amplitude variations, prior probabilities, and likelihoods: A Bayesian ERP study. AB - The capability of the human brain for Bayesian inference was assessed by manipulating probabilistic contingencies in an urn-ball task. Event-related potentials (ERPs) were recorded in response to stimuli that differed in their relative frequency of occurrence (.18 to .82). A veraged ERPs with sufficient signal-to-noise ratio (relative frequency of occurrence > .5) were used for further analysis. Research hypotheses about relationships between probabilistic contingencies and ERP amplitude variations were formalized as (in-)equality constrained hypotheses. Conducting Bayesian model comparisons, we found that manipulations of prior probabilities and likelihoods were associated with separately modifiable and distinct ERP responses. P3a amplitudes were sensitive to the degree of prior certainty such that higher prior probabilities were related to larger frontally distributed P3a waves. P3b amplitudes were sensitive to the degree of likelihood certainty such that lower likelihoods were associated with larger parietally distributed P3b waves. These ERP data suggest that these antecedents of Bayesian inference (prior probabilities and likelihoods) are coded by the human brain. PMID- 27406086 TI - Characterization of morphology and resistance to Blumeria graminis of winter triticale monosomic addition lines with chromosome 2D of Aegilops tauschii. AB - KEY MESSAGE: Allocation of the chromosome 2D of Ae. tauschii in triticale background resulted in changes of its organization, what is related to varied expression of genes determining agronomically important traits. Monosomic alien addition lines (MAALs) are crucial for transfer of genes from wild relatives into cultivated varieties. This kind of genetic stocks is used for physical mapping of specific chromosomes and analyzing alien genes expression. The main aim of our study is to improve hexaploid triticale by transferring D-genome chromatin from Aegilops tauschii * Secale cereale (2n = 4x = 28, DDRR). In this paper, we demonstrate the molecular cytogenetics analysis and SSR markers screening combined with phenotype analysis and evaluation of powdery mildew infection of triticale monosomic addition lines carrying chromosome 2D of Ae. tauschii. We confirmed the inheritance of chromosome 2D from the BC2F4 to the BC2F6 generation of triticale hybrids. Moreover, we unveiled a high variable region on the short arm of chromosome 2D, where chromosome rearrangements were mapped. These events had direct influence on plant height of hybrids what might be connected with changes at Rht8 loci. We obtained 20 semi-dwarf plants of BC2F6 generation carrying 2D chromosome with the powdery mildew resistance, without changes in spike morphology, which can be used in the triticale breeding programs. PMID- 27406087 TI - Ectopic expression and functional characterization of type III polyketide synthase mutants from Emblica officinalis Gaertn. AB - KEY MESSAGE: Functional characterization and ectopic expression studies of chalcone synthase mutants implicate the role of phenylalanine in tailoring the substrate specificity of type III polyketide synthase. Chalcone synthase (CHS) is a plant-specific type III polyketide synthase that catalyzes the synthesis of flavonoids. Native CHS enzyme does not possess any functional activity on N methylanthraniloyl-CoA, which is the substrate for acridione/quinolone alkaloid biosynthesis. Here, we report the functional transformation of chalcone synthase protein from Emblica officinalis (EoCHS) to quinolone and acridone synthase (ACS) with single amino acid substitutions. A cDNA of 1173 bp encoding chalcone synthase was isolated from E. officinalis and mutants (F215S and F265V) were generated by site-directed mutagenesis. Molecular modeling studies of EoCHS did not show any active binding with N-methylanthraniloyl-CoA, but the mutants of EoCHS showed strong affinity to the same. As revealed by the modeling studies, functional analysis of CHS mutants showed that they could utilize p-coumaroyl-CoA as well as N-methylanthraniloyl-CoA as substrates and yield active products such as naringenin, 4-hydroxy 1-methyl 2(H) quinolone and 1,3-dihydroxy-n-methyl acridone. Exchange of a single amino acid in EoCHS (F215S and F265V) resulted in functionally active mutants that preferred N-methylanthraniloyl-CoA over p coumaroyl-CoA. This can be attributed to the increase in the relative volume of active sites in mutants by mutation. Moreover, metabolomic and MS analyses of tobacco leaves transiently expressing mutant genes showed high levels of naringenin, acridones and quinolone derivatives compared to wild-type CHS. This is the first report demonstrating the functional activity of EoCHS mutants with N methylanthraniloyl-CoA and these results indicate the role of phenylalanine in altering the substrate specificity and in the evolution of type III PKSs. PMID- 27406088 TI - A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia. AB - ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11-65 %). The RP2D in this patient population is 225 mg orally once daily. PMID- 27406089 TI - In Vivo Bioluminescence Imaging of Transplanted Mesenchymal Stromal Cells and Their Rejection Mediated by Intrahepatic NK Cells. AB - PURPOSE: Mesenchymal stromal cells (MSCs) hold promise in the treatment of liver disease. However, short survival time of MSCs after intrahepatic transplantation limits their value; therefore, understanding the basis of MSCs survival and rejection may increase their utility. This study was aimed at determining the role of intrahepatic natural killer (NK) cells on MSCs survival and their retention in the liver shortly after transplant. PROCEDURES: Human MSCs were labeled with the Luc2-mKate2 dual-fusion reporter gene (MSCs-R), and the residence time and survival of MSCs-R xenografts after intrahepatic transplantation were evaluated by in vivo bioluminescence imaging (BLI). Coculture of MSCs and NK cells was performed to assess cytotoxicity. To evaluate the role of NK cells in rejection of the xenografted cells, the fates of transplanted MSCs-R were then assessed in vivo by BLI after activation of intrahepatic NK cells. RESULTS: We observed a linear correlation between luciferase activity from live MSCs-R and cell number in vitro (R 2 = 0.9956). In vivo, we observed a gradual decline in bioluminescent signals from transplanted MSCs-R over a region corresponding to the liver in both the control group and the NK-activated group. However, the survival time and retention of intrahepatic MSCs R decreased more rapidly in the NK-activated group of mice compared to the control group. This indicated that activated NK cells accelerate the elimination of transplanted MSCs. Also, we found that the number of hepatic NK cells and the expression of NK activation markers significantly increased after intrahepatic delivery of MSCs. This suggested that resident NK cells, in a resting state, were activated by intrahepatic transplantation of human MSCs. Taken together, the data suggests that activated hepatic NK cells mediate, in part, rejection of the MSCs xenografts. Cytotoxicity assays showed that activated NK cells may inhibit the proliferation of MSCs and, to a certain extent, induce MSCs death. CONCLUSION: Human MSCs could be followed dynamically in vivo by BLI, and the role of murine hepatic NK cells, especially activated NK cells, could be inferred from the loss of signals from MSCs. This finding may have practical clinical implications in MSCs transplantation in treating liver disease. PMID- 27406090 TI - Radiolabeling and Preliminary Evaluation of Ga-68 Labeled NODAGA-Ubiquicidin Fragments for Prospective Infection Imaging. AB - PURPOSE: The present work was aimed at the development of prospective positron emission tomography (PET) agents for infection imaging. Towards this aim, ubiquicidin (UBI) fragments conjugated with the macrocyclic NODAGA chelator were radiolabeled with Ga-68 and evaluated. PROCEDURES: Conformations of custom synthesized NODAGA-UBI (29-41) and NODAGA-UBI (31-38) conjugates were compared with UBI (29-41) by circular dichroism (CD) spectroscopy. Optimization of labeling of NODAGA conjugates of UBI peptides with Ga-68 was performed and quality control analysis was carried out by chromatography techniques. In vitro uptake of [68Ga] NODAGA-UBI (29-41) and [68Ga]NODAGA-UBI (31-38) was studied in Staphylococcus aureus cells. In vivo distribution of [68Ga]GaCl3 and [68Ga]NODAGA UBI complexes was performed in normal Swiss mice. RESULTS: Conformations of NODAGA-UBI (29-41) and NODAGA-UBI (31-38) conjugates were found to be similar to UBI (29-41). NODAGA-UBI conjugates could be consistently labeled with Ga-68 in high radiochemical yields (>95 %) with high radiochemical purity (>95 %). [68Ga]NODAGA-UBI (29-41) and [68Ga]NODAGA-UBI (31-38) complexes showed retention time of 14 and 14.5 min, respectively, by HPLC radiochromatogram. Specific uptake of [68Ga]NODAGA-UBI fragments was observed in S.aureus cells. Greater than 64 % of the injected dose was cleared via the renal route at 1 h post injection, and no significant uptake in vital organs of mice was observed with both the agents. CONCLUSION: This is the first report on Ga-68 labeled NODAGA-UBI fragments for infection imaging and the agents hold tremendous prospect in PET imaging. PMID- 27406091 TI - Factors associated with the non-use of insecticide-treated nets in Rwandan children. AB - BACKGROUND: Insecticide-treated bed nets (ITNs) are highly effective in reducing malaria burden when used properly. However, factors related to individuals, households and community may influence how ITNs are used for malaria control. The study examined influences exerted at these levels to determine if they are associated with ITN non-use among children under 5 years of age in Rwanda. METHODS: Using data from the 2010 Rwanda Demographic Health Survey, the investigation was done on the factors associated with ITN non-use among children under 5 years. Descriptive statistics as well as univariate and multilevel logistic regression analyses were used to identify factors associated with ITN non-use. RESULTS: Responses from a total of 6173 women aged 15-49 years living in 492 villages were included in the analysis. Risk factors for children not utilizing ITNs (25 %) included: (Odds ratio [95 % confidence interval]) households with more than five members (1.42 [1.23-1.63]), employed mother (1.33 [1.06-1.66]), and lower household altitude (1.36 [1.14-1.61]). Protective risk factors for ITN use included households with more than three nets (0.39 [0.33 0.47]), mothers who attended one to four visits at antenatal clinics during pregnancy (0.45 [0.29-0.69]), more than four antenatal clinic visits during pregnancy (0.39 [0.21-0.70]), mothers married or living with partner (0.43 [0.36 0.52]), mothers with any education level (0.77 [0.65-0.91]), and households with higher community wealth quintile (0.71 [0.59-0.84]). CONCLUSIONS: Rwanda has achieved high coverage of ITN use and proper use has contributed to a decline in malaria in Rwanda; however, maintaining universal ITN coverage is not enough to protect citizens from this disease. Risk factors related to ITN non-use at individual, household and community level include poverty, education, birth spacing, and antenatal clinic attendance. There is a need to address findings with strategies to mitigate the non-use of ITNs for effective malaria prevention in Rwanda. PMID- 27406092 TI - Editorial: Management Based on Risk: Individualizing the Care of the Breast Cancer Patient. PMID- 27406093 TI - Operative and Oncologic Outcomes in 9861 Patients with Operable Breast Cancer: Single-Institution Analysis of Breast Conservation with Oncoplastic Reconstruction. AB - BACKGROUND: Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer. METHODS: This retrospective cohort study interrogated a single institution's prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed. RESULTS: There were 10,607 operations performed for 9861 patients. Median follow up was 3.4 years (range, 0-9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R. CONCLUSIONS: Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM. PMID- 27406094 TI - Intraoperative Margin Assessment in Wire-Localized Breast-Conserving Surgery for Invasive Cancer: A Population-Level Comparison of Techniques. AB - BACKGROUND: Various intraoperative margin assessment techniques have been shown to improve margin status in breast-conserving surgery (BCS) for cancer. Our study sought to evaluate multiple margin assessment techniques on a population level and determine their effects on margin status. METHODS: Patients undergoing wire localized BCS for invasive cancer in Alberta, Canada, were assessed using a prospectively entered database of patient and tumor characteristics. Margin status was obtained from chart review. Four margin assessment techniques were studied: specimen mammography (SM), intraoperative ultrasound (US), gross assessment by pathologist (GP), and frozen section analysis (FS). Multivariable logistic regression adjusting for confounders was used to assess effect of any technique on margin status, with secondary analysis evaluating effects of individual techniques. RESULTS: Margin assessment was performed in 1165 of 1649 patients (71 %). The overall positive margin rate was 20.8 %. Adjusting for confounders, we found no difference in the odds of a positive margin with any margin assessment technique versus wire localization alone (OR 0.79, p = 0.22, 95 % CI 0.54-1.16). Individually, both GP and FS reduced the risk of a positive margin (GP-OR 0.56, p = 0.002, 95 % CI 0.39-0.81; FS-OR 0.43, p = 0.046, 95 % CI 0.19-0.98), whereas SM and US showed no effect (SM-OR 1.23, p = 0.29, 95 % CI 0.84-1.81; US-OR 1.09, p = 0.83, 95 % CI 0.50-2.37). CONCLUSIONS: Use of any margin assessment technique did not improve margin status compared to wire localization alone. Gross assessment by pathologist and frozen section analysis improved margin status compared to imaging-alone techniques. Further exploration is required to refine optimal margin assessment methods. PMID- 27406095 TI - Factors Associated with Recurrence Rates and Long-Term Survival in Women Diagnosed with Breast Cancer Ages 40 and Younger. AB - BACKGROUND: Young age at breast cancer diagnosis has been associated with increased risk of recurrence and mortality. We reevaluated this assumption in a large, modern cohort of women diagnosed with breast cancer at age <=40 years. METHODS: We identified women with breast cancer at age <=40 years at a single institution from 1996-2008. We assessed locoregional recurrence (LRR), distant recurrence, disease-free survival (DFS), and overall survival (OS), and correlated patient and tumor characteristics with outcomes. RESULTS: We identified 584 women aged <=40 years with breast cancer. Median age was 37 years, and median follow-up was 124 months; 61.5 % were stages 0-I and 38.5 % were stages II-III. Overall, 57.4 % had lumpectomies and 42.5 % mastectomies. DFS was 93 % at 5 years and 84.5 % at 10 years. OS was 93 % at 5 years and 86.5 % at 10 years. On multivariate analysis, worse DFS was associated with positive nodes (p = 0.002); worse OS was associated with larger tumor size (p = 0.042). When stratified by lumpectomy versus mastectomy, there were no significant differences in survival or recurrence. For lumpectomy patients, DFS was 96 % at 5 years and 88 % at 10 years; OS was 96 % at 5 years and 89 % at 10 years. For mastectomy patients, DFS was 89.5 % at 5 years and 79 % at 10 years; OS was 90 % at 5 years and 83 % at 10 years. Lumpectomy LRR rates were 1 % at 5 years and 4 % at 10 years. Mastectomy LRR rates were 3.5 % at 5 years and 8.7 % at 10 years. CONCLUSIONS: Outcomes for women with breast cancer at age <=40 years have improved. Lumpectomy recurrence rates are low, suggesting that lumpectomy is oncologically safe for young breast cancer patients. PMID- 27406096 TI - Nipple-Sparing Mastectomy: Indications, Contraindications, Risks, Benefits, and Techniques. PMID- 27406097 TI - Prognostic Impact of Port-Site Metastasis After Diagnostic Laparoscopy for Epithelial Ovarian Cancer. AB - BACKGROUND: This study was designed to evaluate the prevalence, morbidity, and prognostic impact of port-site metastasis (PSM) in patients with epithelial ovarian cancer (EOC) undergoing laparoscopy before subsequent primary debulking surgery (PDS). METHODS: All consecutive patients treated between 2000 and 2014, who had a laparoscopy followed by PDS, were extracted from our prospectively maintained database. All patients with histological examination of port-sites were included in this unicentric exploratory analysis. RESULTS: A total of 250 (25.5 %) of 982 patients with EOC underwent laparoscopy before PDS. Port-site resection was performed in those 214 (85.6 %) patients in whom a complete or almost complete resection with residuals <=1 cm was achieved. Median interval between laparoscopy and PDS was 25 days. PSM was detected in 100 of 214 patients (46.7 %). Risk factors for PSM were higher tumor stage (odds ratio [OR] 13.5, 95 % confidence interval [CI] 2.9-62.0, p = 0.04), positive lymph node status (OR 3.0, 95 % CI 1.3-6.7, p = 0.009), and ascites >500 mL (OR 3.9, 95 % CI 1.5-10.0, p = 0.005). Wound healing disorders and postoperative morbidity were significantly higher in patients with PSM (Clavien-Dindo Classification grade 3 5: 41.0 vs. 14.9 %, p < 0.001). However, multivariate Cox-regression models did not identify PSM as independent prognostic factor. CONCLUSIONS: The prevalence of PSM after laparoscopy in EOC patients is considerably high. PSM had no impact on survival; however, PSM were associated with more postoperative complications and a higher surgical treatment burden. This should be balanced with the expected benefit when laparoscopy is considered for the management of EOC. PMID- 27406098 TI - Transthoracic Anastomotic Leak After Esophagectomy: Current Trends. AB - INTRODUCTION: Leaks from intrathoracic esophagogastric anastomosis are thought to be associated with higher rates of morbidity and mortality than leaks from cervical anastomosis. We challenge this assumption and hypothesize that there is no significant difference in mortality based on the location of the esophagogastric anastomosis. METHODS: A systematic literature search was conducted using PubMed and Embase databases on all studies published from January 2000 to June 2015, comparing transthoracic (TTE) and transhiatal (THE) esophagectomies. Studies using jejunal or colonic interposition were excluded. Outcomes analyzed were leak rate, leak-associated mortality, overall 30-day mortality, and overall morbidity. Meta-analyses were performed using Mantel Haenszel statistical analyses on studies reporting leak rates of both approaches. Nominal data are presented as frequency and interquartile range (IQR); measures of the association between treatments and outcomes are presented as odds ratio (OR) with 95 % confidence interval. RESULTS: Twenty-one studies (3 randomized controlled trials) were analyzed comprising of 7167 patients (54 % TTE). TTE approach yields a lower anastomotic leak rate (9.8 %; IQR 6.0-12.2 %) than THE (12 %; IQR 11.6-22.1 %; OR 0.56 [0.34-0.92]), without any significant difference in leak associated mortality (7.1 % TTE vs. 4.6 % THE: OR 1.83 [0.39-8.52]). There was no difference in overall 30-day mortality (3.9 % TTE vs. 4.3 % THE; OR 0.86 [0.66-1.13]) and morbidity (59.0 % TTE vs. 66.6 % THE; OR 0.76 [0.37-1.59]). DISCUSSION: Based on meta-analysis, TTE is associated with a lower leak rate and does not result in higher morbidity or mortality than THE. The previously assumed higher rate of transthoracic anastomotic leak-associated mortality is overstated, thus supporting surgeon discretion and other factors to influence the choice of thoracic versus cervical anastomosis. PMID- 27406100 TI - Should the NHS abolish the purchaser-provider split? PMID- 27406099 TI - Inpatient gradual diagnostics and its relevance for determining treatment strategies in lumbar back pain. AB - BACKGROUND: Identifying patients who will benefit from spine surgery is still a challenge. This is especially the case when patients' complaints and medical history, together with clinical observations, do not correspond to structural pathological changes. With inpatient gradual diagnostics (IGD)-the administration of analgesic and anti-inflammatory agents to a special area of interest-the effect of surgery can be temporarily simulated. From the patient's statement about the alleviation of pain, the surgeon can draw conclusions concerning its causes. The aim of this study was to evaluate the extent to which IGD influences the decision about the nature and scope of surgical treatment strategies, and the way in which it does so, in patients with chronic lumbar back pain. METHODS: Clinical history and radiologic images were analysed retrospectively in 116 patients by two spine surgeons. Two therapeutic recommendations were developed for each patient: one was based on knowledge before IGD and one on knowledge after IGD. RESULTS: IGD changed the treatment strategy in 39 % of the analysed cases. Although the rate of recommended surgery was reduced by about 10 %, the indicated surgical scope increased in 25 % of cases. CONCLUSIONS: IGD is an established concept used to determine therapeutic strategies in patients with chronic lumbar back pain. In our analysed cases, IGD led to highly relevant changes in recommendations for further surgical treatment. PMID- 27406101 TI - Effect of Polyester and Plaster of Paris Casts on Determination of Volumetric Bone Mineral Density Assessed by Peripheral Quantitative Computed Tomography (pQCT). AB - Peripheral quantitative computed tomography (pQCT) is a non-invasive, low radiation tool for measuring volumetric bone mineral density. It has potential for use in fracture healing applications; however, the unknown attenuation effects of cast material on peripheral quantitative computed tomography have contributed to its limited use in this area. The effect of two common cast materials, polyester and Plaster of Paris was investigated by performing both in vitro and in vivo studies. The in vitro study tested the effect of increasing layers of cast material on bone density measurements performed on a hydroxyapatite phantom. Cast thickness was directly associated with a reduction in bone mineral density, with twelve layers of polyester and Plaster of Paris resulting in a 0.55 and 2.21 % decrease in bone density measurements. Precision error in situ with polyester cast material was 0.71 %, and 2.31 % with Plaster of Paris cast material. The in vivo study comprised a prospective trial with 28 healthy adult participants to evaluate the effect of the two cast materials. Trabecular bone mineral density was increased by 0.5 % in the presence of a polyester cast and decreased by 4.22 % in the presence of a Plaster of Paris cast. Cortical bone mineral density was decreased by 3.46 and 5.54 % for polyester and Plaster of Paris, respectively. This study quantified the effects of orthopaedic casts on pQCT-derived bone parameters. The results suggest applicability of commonly utilised cast materials in combination with pQCT to assess fracture healing. PMID- 27406102 TI - Influence of a School-based Physical Activity Intervention on Cortical Bone Mass Distribution: A 7-year Intervention Study. AB - Cortical bone mass and density varies across a bones length and cross section, and may be influenced by physical activity. This study evaluated the long-term effects of a pediatric school-based physical activity intervention on tibial cortical bone mass distribution. A total of 170 children (72 girls and 98 boys) from one school were provided with 200 min of physical education per week. Three other schools (44 girls and 47 boys) continued with the standard 60 min per week. Tibial total and cortical area, cortical density, polar stress-strain index (SSI), and the mass and density distribution around the center of mass (polar distribution, mg) and through the bones cortex (radial distribution subdivided into endo-, mid-, and pericortical volumetric BMD: mg/cm3) at three sites (14, 38, and 66 %) were assessed using peripheral quantitative computed tomography after 7 years. Girls in the intervention group had 2.5 % greater cortical thickness and 6.9 % greater SSI at the 66 % tibia, which was accompanied by significantly greater pericortical volumetric BMD compared to controls (all P < 0.05). Region-specific differences in cortical mass were also detected in the anterior, medial, and lateral sectors at the 38 and 66 % tibial sites. There were no group differences at the 14 % tibia site in girls, and no group differences in any of the bone parameters in boys. Additional school-based physical education over seven years was associated with greater tibial structure, strength, and region-specific adaptations in cortical bone mass and density distribution in girls, but not in boys. PMID- 27406104 TI - Carotid-Cavernous Fistula: A Rare but Treatable Cause of Rapidly Progressive Vision Loss. PMID- 27406103 TI - Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results From a Multicenter Study. AB - BACKGROUND AND PURPOSE: Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator. METHODS: This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses. RESULTS: We evaluated 992 patients (mean age, 74.0+/-12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3-27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6-14.1) increased the risk of rPH. CONCLUSIONS: The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions. PMID- 27406105 TI - Family History and Risk of Recurrent Stroke. AB - BACKGROUND AND PURPOSE: The association between family history of stroke and stroke recurrence remains unclear. METHODS: Using a web-based multicenter stroke registry database, information on history of stroke in first-degree relatives was collected prospectively for acute ischemic stroke patients who were hospitalized within 7 days of onset. The collected information was categorized as follows: type of the affected relative(s) with stroke (paternal, maternal, sibling, or 2 or more) and age of the relative's stroke onset (<50, 50-59, 60-69, and >=70 years). Stroke recurrence was captured prospectively using a predetermined protocol. Subgroup analyses were performed according to the patient's age at the index stroke. RESULTS: Among 7642 patients, 937 (12.3%) had a history of stroke in their first-degree relatives and 475 (6.2%: 201 within and 274 after 3 weeks from index stroke) experienced stroke recurrence (median follow-up, 365 days). In multivariable Cox proportional hazard models, overall family history was not associated with stroke recurrence (hazard ratio, 1.08; 95% confidence interval, 0.81-1.43). However, the details of their family histories, including relative's age at stroke onset (<50 years: hazard ratio, 2.14; 95% confidence interval, 1.004-4.54) and stroke history in a sibling (hazard ratio, 1.67; 95% confidence interval, 1.09-2.58), were independently associated with stroke recurrence after adjusting for potential confounders. The associations appeared to be stronger in young adults with stroke (age, <55 years) than in older stroke patients. CONCLUSIONS: This study suggests that elevated risks of recurrent stroke are associated with having relatives with early-onset stroke and siblings with stroke histories, implying that additional precautions may be needed in such populations. PMID- 27406106 TI - Long-Term Outcome After Carotid Artery Stenting: A Population-Based Matched Cohort Study. AB - BACKGROUND AND PURPOSE: Long-term outcome after carotid artery stenting (CAS), a less invasive technique than carotid endarterectomy (CEA), for prevention of stroke, is unclear. The aim was to assess long-term outcomes after CAS, compared with CEA, in a nationwide cohort study. METHODS: All patients registered in the national Swedish Vascular Registry (Swedvasc) treated with primary CAS between 2005 and 2012 were identified. For every CAS, 2 CEA controls, matched for sex, age, procedure year, and indication (symtomatic/asymtomatic), were chosen. Postoperative stroke was identified by cross-matching the cohort with the InPatient Registry and charts review. Primary end point was ipsilateral stroke or death >30 days postoperatively. RESULTS: A total of 1157 patients were included, 409 CAS and 748 CEA; 73% men with mean age 70 years and 69% were symptomatic. Risk factor profile was similar between the 2 groups. Median follow-up time was 4.1 years. Ipsilateral stroke or death of >30 days postoperatively occurred in 95 of 394 in the CAS group versus 120 of 724 in the CEA group (adjusted hazard ratio, 1.59; 95% confidence interval, 1.15-2.18). The corresponding adjusted rates for death, ipsilateral stroke of >30 days, and any stroke or death of >30 days were 25.7% versus 18.6% (hazard ratio, 1.20; 95% confidence interval, 0.84 1.72), 9.4% versus 2.9% (hazard ratio, 3.40; 95% confidence interval, 1.53-7.53), 34.2% versus 23.6% (hazard ratio, 1.49; 95% confidence interval, 1.10-2.00) for the CAS group versus CEA group, respectively. CONCLUSIONS: In this nationwide cohort study, CAS was associated with an increased long-term risk of ipsilateral stroke and death during after the perioperative phase when compared with CEA. PMID- 27406107 TI - Seek and Ye Shall Find Fibrillations. PMID- 27406109 TI - Underutilization of Ambulatory ECG Monitoring After Stroke and Transient Ischemic Attack: Missed Opportunities for Atrial Fibrillation Detection. AB - BACKGROUND AND PURPOSE: Detection and treatment of atrial fibrillation is a major goal in secondary stroke prevention. Guidelines recommend at least 24 hours of ECG monitoring after stroke. However, it is unclear how often this is done in routine practice. METHODS: In this longitudinal cohort study using data from the Ontario Stroke Registry, we analyzed consecutive patients presenting to designated stroke centers in Ontario, Canada (2003-2013) with a first acute ischemic stroke or transient ischemic attack (TIA) in sinus rhythm and without known atrial fibrillation. The primary outcome was the proportion of patients who received at least 24-hour Holter monitoring within 30 days after stroke/TIA. Secondary analyses assessed total duration of ECG monitoring completed within 90 days after stroke/TIA, temporal trends in monitoring use, and use of Holter monitoring relative to echocardiography. RESULTS: Among 17 398 consecutive eligible patients (mean age 68.8+/-14.3 years), 30.6% had at least 24 hours of Holter monitoring within 30 days after stroke/TIA. Less than 1% of patients received prolonged monitoring beyond 48 hours. The median time to start monitoring was 9 days poststroke (interquartile range 3-25). Stroke/TIA patients were nearly twice as likely to receive an echocardiogram than a Holter monitor within 90 days (odds ratio 1.8, 95% confidence interval 1.67-2.01). CONCLUSIONS: Less than one third of patients in our cohort received guideline-recommended 24 hour Holter monitoring, and <1% received prolonged ambulatory ECG monitoring. These findings highlight a modifiable evidence-practice gap that likely contributes to an overdiagnosis of strokes as cryptogenic, an underdiagnosis of atrial fibrillation, and missed anticoagulant treatment opportunities for secondary stroke prevention. PMID- 27406110 TI - Pesticide Health and Safety Challenges Facing Informal Sector Workers: A Case of Small-scale Agricultural Workers in Tanzania. AB - The Tanzania informal sector is growing fast, with precarious working conditions and particular hazards for women and children in agriculture. Hazardous agricultural chemicals including pesticides are mostly imported and have been used for many years. Despite the role played by pesticides in food security and vector control, these chemicals are responsible for acute and chronic illnesses among communities. The availability of obsolete persistent organic pesticides on the open market indicates existence of an inadequate regulatory system. People who get injured or ill in the agriculture sector in Tanzania receive health services in primary health care facilities where professionals have little or no knowledge of pesticides. We are presenting the pesticide health and safety challenges faced by small-scale farmers who fall in the informal sector. Achievements that have been made by the government and other players to reduce and prevent pesticide exposures and poisoning are also outlined. PMID- 27406108 TI - Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke. AB - Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine prespecified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favored, with justification for considering deaths and severe disability jointly. Because trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines >=2 such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care. PMID- 27406111 TI - Extending Occupational Health and Safety to Urban Street Vendors: Reflections From a Project in Durban, South Africa. AB - This article focuses on an action-research project which is attempting to extend occupational health and safety to a group of street traders in Durban, South Africa, using a variety of different (and sometimes unconventional) institutional actors. The article is written from the perspective of key people who have played a role in conceptualizing and administering the project and is intended to deepen the conversation about what it means to extend occupational health to the informal economy. It explores this question through a reflection on three key project activities: the setting up of a trader-led health and safety committee, an occupational health and safety training course, and a clinical health assessment. It concludes with a discussion of the issues that emerge from the reflections of project participants, which include the need to bring occupational health and urban health into closer conversation with one another, the need to be cognizant of local "informal" politics and the impact that has on occupational health and safety interventions, and the need to create greater opportunities for occupational health and safety professionals to interact with workers in the informal economy. PMID- 27406112 TI - Land, Life, and Security: An Interview with Edgardo Garcia, Secretary General of the Association of Farm Workers in Nicaragua. AB - This is an interview with Edgardo Garcia, Secretary General of the Association of Farm Workers in Nicaragua and Oscar Berrios from the Nicaraguan National Engineering University. The interview was conducted in Nicaragua in October 2013. Garcia and Berrios address the importance of organizing among formal workers and informal workers, and the shared conditions of both in Nicaragua. They highlight the history and context of the agricultural workers who began organizing during the national armed revolutionary war, the role of government to create conditions for healthy and safe work, and the need for workers to organize and advocate for themselves. Finally, they highlight the importance of solidarity among workers and the need for alliances with unions and technical assistance providers around the world. PMID- 27406113 TI - Does Informal Employment Exist in the United States and Other Developed Countries? AB - This editorial argues that informal employment does exist in developed countries and needs to be studied as such to complement the existing literature mostly published on informal work in developing countries. PMID- 27406114 TI - Aniseikonia and Foveal Microstructure in Patients with Idiopathic Macular Hole. AB - PURPOSE: To quantify the severity of aniseikonia in patients undergoing vitrectomy for idiopathic macular hole (MH) and to examine any relationship between aniseikonia and the foveal microstructure. DESIGN: Prospective, consecutive, interventional case series. PARTICIPANTS: We included 56 eyes of 56 patients who underwent vitrectomy to treat idiopathic MH. METHODS: We examined visual acuity, aniseikonia using the New Aniseikonia Test, and foveal structure using optical coherence tomography (OCT) before and 3, 6, and 12 months after surgery. Based on OCT images, minimum and base diameters of MH, height of MH, and defect lengths of the external limiting membrane (ELM), ellipsoid zone, and interdigitation zone were assessed. MAIN OUTCOME MEASURES: Degree of aniseikonia before and after surgery. RESULTS: The mean aniseikonia was -3.2+/-4.6%, ranging from -15.5% to +5.0%. Of the patients, 55% had micropsia, 7% had macropsia, and 38% had no aniseikonia. The mean absolute value of aniseikonia improved significantly from 3.8+/-4.1% before surgery to 1.0+/-1.5% at 12 months after surgery (P < 0.0001). The preoperative mean absolute value of aniseikonia showed a significant correlation with minimum diameters of MH (P < 0.01), base diameters of MH (P < 0.01), and the defect length of ELM (P < 0.05). In multivariate analysis, preoperative aniseikonia showed a significant correlation with the defect length of ELM (P < 0.05). In contrast, postoperative aniseikonia was not associated with any of the parameters. CONCLUSIONS: Approximately half of MH patients had micropsia. Vitrectomy for MH improved aniseikonia. Preoperative aniseikonia was associated with MH size and the defect length of ELM. PMID- 27406116 TI - HDL metrics, let's call the number thing off? PMID- 27406115 TI - First Prospective Cohort Study of Diabetic Retinopathy from Sub-Saharan Africa: High Incidence and Progression of Retinopathy and Relationship to Human Immunodeficiency Virus Infection. AB - PURPOSE: To describe the prevalence, incidence, and progression of retinopathy and to report associations with demographic, clinical, and biochemical variables in people with diabetes in Southern Malawi. DESIGN: Prospective cohort study. PARTICIPANTS: Subjects were systematically sampled from 2 primary care diabetes clinics. METHODS: We performed the first prospective cohort study of diabetic retinopathy from Sub-Saharan Africa over 24 months. Visual acuity, glycemic control, blood pressure, human immunodeficiency virus (HIV) status, urine albumin to-creatinine ratio, hemoglobin, and lipids were assessed. Retinopathy was graded at an accredited reading center using modified Wisconsin grading of 4-field mydriatic photographs. MAIN OUTCOME MEASURES: Incidence of sight-threatening retinopathy and progression of retinopathy by 2 steps on the Liverpool Diabetic Eye Study Scale. RESULTS: A total of 357 subjects were recruited to the 24-month cohort study. At baseline, 13.4% of subjects were HIV positive and 15.1% were anemic. The 2-year incidence of sight-threatening diabetic retinopathy (STDR) for subjects with level 10 (no retinopathy), level 20 (background), and level 30 (preproliferative) retinopathy at baseline was 2.7% (95% confidence interval [CI], 0.1-5.3), 27.3% (95% CI, 16.4-38.2), and 25.0% (95% CI, 0-67.4), respectively. In a multivariate logistic analysis, 2-step progression of diabetic retinopathy was associated with glycosylated hemoglobin (odds ratio [OR], 1.27; 95% CI, 1.12-1.45), baseline grade of retinopathy (OR, 1.39; 95% CI, 1.02-1.91), and HIV infection (OR, 0.16; 95% CI, 0.03-0.78). At 2 years, 17 subjects (5.8%) lost >=15 letters. CONCLUSIONS: Incidence of STDR was approximately 3 times that reported in recent European studies. The negative association of HIV infection with retinopathy progression is a new finding. PMID- 27406117 TI - Trophic structure of a coastal fish community determined with diet and stable isotope analyses. AB - A combination of dietary guild analysis and nitrogen (delta(15) N) and carbon (delta(13) C) stable-isotope analysis was used to assess the trophic structure of the fish community in Rhode Island and Block Island Sounds, an area off southern New England identified for offshore wind energy development. In the autumn of 2009, 2010 and 2011, stomach and tissue samples were taken from 20 fish and invertebrate species for analysis of diet composition and delta(15) N and delta(13) C signatures. The food chain in Rhode Island and Block Island Sounds comprises approximately four trophic levels within which the fish community is divided into distinct dietary guilds, including planktivores, benthivores, crustacivores and piscivores. Within these guilds, inter-species isotopic and dietary overlap is high, suggesting that resource partitioning or competitive interactions play a major role in structuring the fish community. Carbon isotopes indicate that most fishes are supported by pelagic phytoplankton, although there is evidence that benthic production also plays a role, particularly for obligate benthivores such as skates Leucoraja spp. This type of analysis is useful for developing an ecosystem-based approach to management, as it identifies species that act as direct links to basal resources as well as species groups that share trophic roles. PMID- 27406118 TI - Dementia-friendly communities: challenges and strategies for achieving stakeholder involvement. AB - Dementia-friendly communities (DFCs) are a UK policy initiative that aims to enable people with dementia to feel supported and included within their local community. Current approaches to DFC creation rely on stakeholder involvement, often requiring volunteer assistance. There is though a lack of evidence that examines the reality of achieving this. This paper critically assesses the challenges and strategies for achieving stakeholder involvement in DFCs. The evidence base is drawn from an inter-agency project funded by the National Health Service in the South of England where seven DFCs were developed by steering group partners and four part-time project workers (PWs). Data from the independent evaluation undertaken in the first year (2013-2014) of the project were analysed: 14 semi-structured interviews and a focus group examined PWs' experiences; while progress and key milestones are determined from monthly progress forms, good news stories, locality steering group minutes and press releases. Analysis was undertaken using a directed content analysis method, whereby data content for each locality was matched to the analytical framework that was drawn from Alzheimer's Society guidance. Challenges to achieving stakeholder involvement were identified as: establishing networks and including people representative of the local community; involving people affected by dementia; and gaining commitment from organisations. Strategies for achieving stakeholder involvement were recognised as: a sustainable approach; spreading the word; and sharing of ideas. By highlighting these challenges and the approaches that have been used within communities to overcome them, these findings form the foundation for the creation of DFC initiatives that will become embedded within communities. Stakeholder involvement is unpredictable and changeable; therefore, reliance on this approach questions the long-term sustainability of DFCs, and must be considered in future policies designed to enhance quality of life for people affected by dementia. PMID- 27406119 TI - Limited precut sphincterotomy combined with endoscopic papillary balloon dilation for common bile duct stone removal in patients with difficult biliary cannulation. AB - BACKGROUND: Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) can result in failure of common bile duct (CBD) stone removal and pancreatitis. The present study aimed to report the efficacy and safety of limited precut sphincterotomy (PS) combined with endoscopic papillary balloon dilation (EPBD) for CBD stone removal in patients with difficult biliary cannulation, and the complications associated with this combined procedure. METHODS: A total of 3305 patients underwent ERCP in our hospital between October 2009 and September 2014 and 258 were diagnosed with difficult biliary cannulation. Of these 258 patients, 58 underwent limited PS combined with EPBD for CBD stone removal, and these 58 patients were included in this retrospective study. RESULTS: The overall success rate was 94.8 % (55/58), and the success rate for single-session removal was 87.9 % (51/58). The mean procedure time was 41 +/- 11.48 min (range, 20-72 min). Mechanical lithotripsy was needed in 10.3 % (6/58) of patients. Procedure-related complications included bleeding in 3.4 % (2/58), pancreatitis in 8.6 % (5/58) and biliary tract infection (BTI) in 1.7 % (1/58) of patients. CONCLUSIONS: The therapeutic outcome of limited PS combined with EPBD for CBD stone removal in patients with difficult biliary cannulation was good with an acceptable complication rate. It could be an alternative to PS and "early" limited PS should be used for prompt identification of the bile duct. Limited PS combined with EPBD is safe and effective for CBD stone removal in patients with difficult biliary cannulation. PMID- 27406121 TI - Evergreen Planar Chromatography: Editorial. PMID- 27406120 TI - Recurrent corneal melting in the paraneoplastic pemphigus associated with Castleman's disease. AB - BACKGROUND: The ocular presentation of Castleman's disease (CD)-associated paraneoplastic pemphigus (PNP) has rarely been reported. In this report, we describe a young patient with CD-associated PNP who had recurrent corneal ulceration in addition to cicatrizing conjunctivitis. CASE PRESENTATION: We describe a case of 23-year-old male with mucocutaneous erosion and conjunctival injection and erosion who was found to have PNP. Pelvic hyaline-vascular CD was detected and completely excised. The mucocutaneous lesions improved postoperatively. Two years after pelvic surgery, the patient gradually developed conjunctival symblepharon in both eyes and pterygium in the right eye. The patient then underwent a successful exclusion of the symblepharon, an excision of the pterygium and an amniotic membrane transplantation in the right eye. However, after 6 months, he experienced an aseptic corneal ulcer and recurrent pterygiumin the right eye. After treatment with systemic and local immunosuppressive medications, the corneal ulcer gradually healed and remained stable. CONCLUSION: Corneal ulceration and melting, in addition to conjunctivitis, as a complication of CD-associated PNP, can be successfully managed with systemic and local immunosuppressants. PMID- 27406122 TI - HPTLC Method for Estimation of Topiramate in Solubility Studies, Diffusion Studies, Plasma, Brain Homogenate and Pharmaceutical Formulation. AB - Topiramate, 2,3:4,5-bis-O-(1-methylethylidene)-beta-d-fructopyranose, is an anticonvulsant drug indicated in the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures in adults and children. An economic and rapid high-performance thin-layer chromatographic (HPTLC) method was developed and was validated for the quantitative determination of topiramate in plasma, brain homogenate and pharmaceutical formulation. The simple extraction method was used for the isolation of topiramate from formulation, plasma and brain homogenate samples. HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 plates using toluene : acetone (5.0 : 2.0, v/v) as mobile phase. Spots of developed plates were visualized by spraying of reagent [3.0% phenol in the mixture of ethanol : sulfuric acid (95 : 5, v/v)]. Quantitation was achieved by densitometric analysis at 340 nm over the concentration range of 1,000-5,000 ng/spot. The method was found to give compact spot for the drug (Rf: 0.61 +/- 0.018). The regression analysis data for the calibration plots showed good relationship with a correlation coefficient of 0.9983. The minimum detectable amount was found to be 165 ng/spot, whereas the limit of quantitation was found to be 500 ng/spot. Statistical analysis of the data showed that the method is precise, accurate, reproducible and selective for the analysis of topiramate. The developed method was successfully employed for the estimation of topiramate in samples of equilibrium solubility study, diffusion study, microemulsion formulation and suspension formulation (developed in-house), rat plasma and rat brain homogenate samples. PMID- 27406123 TI - Determination and Pharmacokinetic Study of Pirfenidone in Rat Serum by High Performance Thin-Layer Chromatography. AB - A rapid, sensitive and selective high-performance thin-layer chromatography (HPTLC) method was developed and validated for the determination and pharmacokinetics of pirfenidone in rat serum. One-step protein precipitation by methanol is reported, and serum samples were separated by HPTLC using a simple mobile phase of toluene-methanol in the ratio of 8:2. The retardation factor of pirfenidone in the serum sample was 0.45 with the detection performed at 315 nm. The calibration curve was linear over the range of 100-1,200 ng/spot with a lower limit of quantitation of 40 ng/spot. The mean recovery of pirfenidone in serum was in the range of 70.6-75.8%, and intra-day and inter-day precision were both <14.1%. This method was successfully applied to the pharmacokinetic study of pirfenidone in rats on oral administration of the drug at a dose of 15.0 mg/kg. PMID- 27406124 TI - Simultaneous Determination of Aspirin, Dipyridamole and Two of Their Related Impurities in Capsules by Validated TLC-Densitometric and HPLC Methods. AB - Aspirin (ASP) and dipyridamole (DIP) are widely used as a combination in pharmaceutical formulations for treatment of strokes. Many of these formulations are containing tartaric acid as an excipient (in DIP pellets formulation for sustained release), which increases the probability of formation of dipyridamole tartaric acid ester impurity (DIP-I). On the other hand, salicylic acid (SAL) is considered to be one of the synthesis impurities and a degradation product of ASP. In this work, two chromatographic methods, namely, TLC-densitometry and HPLC, have been established and validated for simultaneous determination of ASP, DIP, SAL and DIP-I. Good separation was achieved by using silica gel as stationary phase and toluene-methanol-ethyl acetate (2:3:5, by volume) as mobile phase in the case of TLC-densitometry and Zorbax ODS column with mobile phase consisting of phosphate buffer (pH 3.3)-acetonitrile-triethylamine (40:60:0.03, by volume) for HPLC. Influence of different organic solvents in mobile phase composition has been studied to optimize the separation efficiency in TLC densitometry. Moreover, factors affecting the efficiency of HPLC, like pH of the buffer used, organic solvent ratio in the mobile phase and flow rate, have been carefully studied using one variable at a time approach. Finally, the proposed methods were validated as per ICH guidelines. PMID- 27406126 TI - A Comparative Study of Chromatographic Behavior and Lipophilicity of Selected Imidazoline Derivatives. AB - Chromatographic behavior and lipophilicity of 20 selected imidazoline derivatives were examined by thin-layer chromatography using CN, RP-2, RP-8 and RP-18 as the stationary phases and a mixture of methanol, water and ammonia as the mobile phase. In all examined chromatographic systems, linear relationships were established between retention parameters and the volume fraction of methanol in the mobile phase (r > 0.985, 0.978, 0.981, 0.988 for the CN, RP-2, RP-8 and RP 18, respectively). The highest correlation between the obtained [Formula: see text] values was observed for RP-2 and RP-8 stationary phases. The experimental lipophilicity indices ([Formula: see text], m and C0) obtained from the retention data were used in correlation study with the calculated logP values. Experimentally determined [Formula: see text] values for all investigated chromatographic systems exhibited the highest correlation with the calculated ClogP values (r: 0.880, 0.872, 0.897 and 0.889 for the CN, RP-2, RP-8 and RP-18 stationary phases, respectively). In addition, principal component analysis enables new information about similarity and differences between tested compounds as well as experimental lipophilicity indices and calculated logP values. Performed QSRR analysis showed that the frequency of C-C at topological distance 1 and CATS2D Lipophilic-Lipophilic at lag 01 were important descriptors with influence on the [Formula: see text] values in all the examined chromatographic systems, while the differences in the retention behavior of compounds on the examined stationary phases can be distinguished based on their specific geometrical, electronic and constitutional properties. PMID- 27406125 TI - Development and Validation of Stability-Indicating HPTLC Method for Estimation of Naratriptan Hydrochloride in Its Pharmaceutical Dosage Form and Its Content Uniformity Testing. AB - The present research project involves development and validation of a stability indicating HPTLC method for the estimation of naratriptan-HCl in their pharmaceutical dosage forms and its content uniformity testing. Naratriptan-HCl was subjected to alkaline, acidic, oxidative, neutral, thermal (dry heat) and photo-degradation conditions. The chromatographic separation was carried out using a precoated silica gel G 60 F254 TLC plate as the stationary phase and dichloromethane-toluene-methanol-triethylamine (4 : 4 : 2 : 1, v/v/v/v) as the mobile phase. The spots of NRT-HCl and its degradation products were detected at 290 nm. The Rf value of NRT-HCl was found to be 0.60 +/- 0.02. The linearity was obtained in the range of 100-500 ng/spot. The limit of detection and limit of quantitation were found to be 6.07 ng/spot and 18.41 ng/spot, respectively. The percentage recovery was found in the range of 98.87-99.55%. NRT-HCl was degraded under acidic, alkaline and oxidative conditions while stable under photolytic, neutral and dry heat conditions. The developed method was applied for estimation of naratriptan-HCl in marketed formulations and its content uniformity testing. PMID- 27406127 TI - HPTLC and Spectrophotometric Estimation of Febuxostat and Diclofenac Potassium in Their Combined Tablets. AB - An accurate, precise, rapid, specific and economic high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitative determination of febuxostat (FEB) and diclofenac potassium (DIC). The chromatographic separation was performed on precoated silica gel 60 GF254 plates with chloroform-methanol 7:3 (v/v) as the mobile phase. The developed plates were scanned and quantified at 289 nm. Experimental conditions including band size, mobile phase composition and chamber-saturation time were critically studied, and the optimum conditions were selected. A satisfactory resolution (Rs = 2.67) with RF 0.48 and 0.69 and high sensitivity with limits of detection of 4 and 7 ng/band for FEB and DIC, respectively, were obtained. In addition, derivative ratio and ratio difference spectrophotometric methods were established for the analysis of such a mixture. All methods were validated as per the ICH guidelines. In the HPTLC method, the calibration plots were linear between 0.01 0.55 and 0.02-0.60 ug/band, for FEB and DIC, respectively. For the spectrophotometric methods, the calibration graphs were linear between 2-14 and 4 18 ug/mL for FEB and DIC, respectively. The simplicity and specificity of the proposed methods suggest their application in quality control analysis of FEB and DIC in their raw materials and tablets. A comparison of the proposed methods with the existing methods is presented. PMID- 27406128 TI - Analysis of 25 C NBOMe in Seized Blotters by HPTLC and GC-MS. AB - Use of unauthorized synthetic drugs is a serious, forensic, regulatory and public health issue. In this scenario, consumption of drug-impregnated blotters is very frequent. For decades, blotters have been generally impregnated with the potent hallucinogen known as lysergic acid diethylamide (LSD); however, since 2013 blotter stamps with N-2 methoxybenzyl-substituted phenylethylamine hallucinogen designated as "NBOMes" have been seized in Chile. To address this issue with readily accessible laboratory equipment, we have developed and validated a new HPTLC method for the identification and quantitation of 25-C-NBOMe in seized blotters and its confirmation by GC-MS. The proposed method was validated according to SWGTOX recommendations and is suitable for routine analysis of seized blotters containing 25-C-NBOMe. With the validated method, we analyzed 15 real samples, in all cases finding 25-C-NBOMe in a wide dosage range (701.0 1943.5 ug per blotter). In this situation, we can assume that NBOMes are replacing LSD as the main hallucinogenic drug consumed in blotters in Chile. PMID- 27406133 TI - The economic burden of asthma and chronic obstructive pulmonary disease and the impact of poor inhalation technique with commonly prescribed dry powder inhalers in three European countries. AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic inflammatory respiratory diseases, which impose a substantial burden on healthcare systems and society. Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting beta2 agonists (LABA), often administered using dry powder inhalers (DPIs), are frequently prescribed to control persistent asthma and COPD. Use of DPIs has been associated with poor inhalation technique, which can lead to increased healthcare resource use and costs. METHODS: A model was developed to estimate the healthcare resource use and costs associated with asthma and COPD management in people using commonly prescribed DPIs (budesonide + formoterol Turbuhaler((r)) or fluticasone + salmeterol Accuhaler((r))) over 1 year in Spain, Sweden and the United Kingdom (UK). The model considered direct costs (inhaler acquisition costs and scheduled and unscheduled healthcare costs), indirect costs (productive days lost), and estimated the contribution of poor inhalation technique to the burden of illness. RESULTS: The direct cost burden of managing asthma and COPD for people using budesonide + formoterol Turbuhaler((r)) or fluticasone + salmeterol Accuhaler((r)) in 2015 was estimated at ?813 million, ?560 million, and ?774 million for Spain, Sweden and the UK, respectively. Poor inhalation technique comprised 2.2-7.7 % of direct costs, totalling ?105 million across the three countries. When lost productivity costs were included, total expenditure increased to ?1.4 billion, ?1.7 billion and ?3.3 billion in Spain, Sweden and the UK, respectively, with ?782 million attributable to poor inhalation technique across the three countries. Sensitivity analyses showed that the model results were most sensitive to changes in the proportion of patients prescribed ICS and LABA FDCs, and least sensitive to differences in the number of antimicrobials and oral corticosteroids prescribed. CONCLUSIONS: The cost of managing asthma and COPD using commonly prescribed DPIs is considerable. A substantial, and avoidable, contributor to this burden is poor inhalation technique. Measures that can improve inhalation technique with current DPIs, such as easier-to-use inhalers or better patient training, could offer benefits to patients and healthcare providers through improving disease outcomes and lowering costs. PMID- 27406134 TI - Characterization of intercellular communication and mitochondrial donation by mesenchymal stromal cells derived from the human lung. AB - BACKGROUND: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of repairing wounded lung epithelial cells by donating cytoplasmic material and mitochondria. Recently, we characterized two populations of human lung-derived mesenchymal stromal cells isolated from digested parenchymal lung tissue (LT MSCs) from healthy individuals or from lung transplant recipients' bronchoalveolar lavage fluid (BAL-MSCs). The aim of this study was to determine whether LT-MSCs and BAL-MSCs are also capable of donating cytoplasmic content and mitochondria to lung epithelial cells. METHODS: Cytoplasmic and mitochondrial transfer was assessed by co-culturing BEAS2B epithelial cells with Calcein AM or Mitotracker Green FM-labelled MSCs. Transfer was then measured by flow cytometry and validated by fluorescent microscopy. Molecular inhibitors were used to determine the contribution of microtubules/tunnelling nanotubes (TNTs, cytochalasin D), gap junctions (carbenoxolone), connexin-43 (gap26) and microvesicles (dynasore). RESULTS: F-actin microtubules/TNTs extending from BM MSCs, LT-MSCs and BAL-MSCs to bronchial epithelial cells formed within 45 minutes of co-culturing cells. Each MSC population transferred a similar volume of cytoplasmic content to epithelial cells. Inhibiting microtubule/TNTs, gap junction formation and microvesicle endocytosis abrogated the transfer of cytoplasmic material from BM-MSCs, LT-MSCs and BAL-MSCs to epithelial cells. In contrast, blocking connexin-43 gap junction formation had no effect on cytoplasmic transfer. All MSC populations donated mitochondria to bronchial epithelial cells with similar efficiency. Mitochondrial transfer was reduced in all co-cultures after microtubule/TNT or endocytosis inhibition. Gap junction formation inhibition reduced mitochondrial transfer in BM-MSC and BAL-MSC co cultures but had no effect on transfer in LT-MSC co-cultures. Connexin-43 inhibition did not impact mitochondrial transfer. Finally, bronchial epithelial cells were incapable of donating cytoplasmic content or mitochondria to any MSC population. CONCLUSION: Similar to their bone marrow counterparts, LT-MSCs and BAL-MSCs can donate cytoplasmic content and mitochondria to bronchial epithelial cells via multiple mechanisms. Given that BM-MSCs utilize these mechanisms to mediate the repair of damaged bronchial epithelial cells, both LT-MSCs and BAL MSCs will probably function similarly. PMID- 27406135 TI - Relationship between performance, dry-land power and kinematics in master swimmers. AB - The purpose of the study was to analyze the relationships between sprint swimming performance, dry-land power, and kinematics in master swimmers. Twenty-two male master swimmers were separated in two groups based on their chronological age: (i) 30-39 years and; (ii) 40-49 years. Maximum dry-land power was determined through counter movement jump and 3 kg medicine ball throwing (Hmax and Tmax, respectively). Kinematic determinants of performance were measured during a maximal bout of 15, 25 and 50 m front crawl (T15, T25, T50). Stroke frequency (SF), stroke length (SL) and stroke index (SI) were calculated as kinematical aspects of the stroke. In the 30-39 group, SI25 was correlated to T25 (r = -0.76, p < 0.01, eta2 = 0.96), the same was observed between SI50 and T50 (r = -0.83, p < 0.01, eta2 = 0.96). Only SI50 was significantly correlated to T50 (r = 0.86, p < 0.01, eta2 = 0.97) in the 40-49 years age cohort. In dryland power variables, Hmax and Tmax were only correlated in the younger master swimmers group (r = 0.87, p < 0.01, eta2 = 0.97). There were no significant differences (p < 0.05) between younger (30-39 years) and older (40-49 years) swimmers groups in dry-land tests (Hmax 28.5 +/- 5.9 vs. 26.5 +/- 3.9 cm and Tmax 4.2 +/- 1.0 vs. 4.2 +/- 1.1 m). Our results suggest that swimming performance in younger master swimmers (30 39 years) seem more dependent on kinematic swimming variables than on strength parameters, which were most related to swimming performance in the older master swimmers (40-49 years). PMID- 27406137 TI - [Not Available]. PMID- 27406136 TI - Outcomes in patients undergoing complex cardiac repairs with cross clamp times over 300 minutes. AB - BACKGROUND: Long cross clamp times have been associated with poor clinical outcomes, yet some patients require extremely long ischemic times to repair complex surgical problems. The purpose of this study was to examine short and mid term survival and to identify risk factors for mortality and morbidity in patients with cross clamp times greater than or equal to 300 min. METHODS: Review of our institution's Society of Thoracic Surgeons database identified 202 patients who underwent surgical procedures necessitating aortic cross clamp times 300 min or greater between 2001 and 2012. Short-term (30-day) clinical outcomes were derived from this database and survival was assessed utilizing the Social Security Death Index. Univariate and multivariate analyses were used to determine the relationship between independent variables and mortality and postoperative outcomes. RESULTS: The average age of the patients was 69.5 +/- 10.6 (mean +/- standard deviation) years and the mean ejection fraction was 52 +/- 12 %. 70.3 % of patients were male. Mean cross clamp time was 346 +/- 45 min, and total bypass time was 421 +/- 70 min. Thirty-day mortality was 12.4 %. The incidence of bleeding and stroke were 6.4 % and 4.0 % respectively. Prolonged ventilation occurred in 26.7 % of patients, and incidence of renal failure was 10.4 %. One, three, five, and seven year survival of the patients who survived the first 30 days post-surgery was 91.9 %, 83.2 %, 75.6 % and 65.7 % respectively. Proportional hazards analysis determined that the statistically significant hazard ratios for mid-term mortality for female gender, age, and prolonged postoperative ventilation were 2.11, 1.04 and 2.72, respectively (p < 0.05 for each). CONCLUSIONS: Cardiac procedures requiring extremely long ischemic times have significant early mortality and morbidity. However, mid-term survival in the patients who survive is good. Decision-making regarding operability in complex cases should allow for long ischemic times. PMID- 27406138 TI - Accuracy of five intraoral scanners compared to indirect digitalization. AB - OBJECTIVES: Direct and indirect digitalization offer two options for computer aided design (CAD)/ computer-aided manufacturing (CAM)-generated restorations. The aim of this study was to evaluate the accuracy of different intraoral scanners and compare them to the process of indirect digitalization. MATERIAL AND METHOD: A titanium testing model was directly digitized 12 times with each intraoral scanner: (1) CS 3500 (CS), (2) Zfx Intrascan (ZFX), (3) CEREC AC Bluecam (BLU), (4) CEREC AC Omnicam (OC) and (5) True Definition (TD). As control, 12 polyether impressions were taken and the referring plaster casts were digitized indirectly with the D-810 laboratory scanner (CON). The accuracy (trueness/precision) of the datasets was evaluated by an analysing software (Geomagic Qualify 12.1) using a "best fit alignment" of the datasets with a highly accurate reference dataset of the testing model, received from industrial computed tomography. RESULTS: Direct digitalization using the TD showed the significant highest overall "trueness", followed by CS. Both performed better than CON. BLU, ZFX and OC showed higher differences from the reference dataset than CON. Regarding the overall "precision", the CS 3500 intraoral scanner and the True Definition showed the best performance. CON, BLU and OC resulted in significantly higher precision than ZFX did. CONCLUSIONS: Within the limitations of this in vitro study, the accuracy of the ascertained datasets was dependent on the scanning system. The direct digitalization was not superior to indirect digitalization for all tested systems. CLINICAL RELEVANCE: Regarding the accuracy, all tested intraoral scanning technologies seem to be able to reproduce a single quadrant within clinical acceptable accuracy. However, differences were detected between the tested systems. PMID- 27406139 TI - Chilcot: physical and mental legacy of Iraq war on UK service personnel. PMID- 27406140 TI - Trans-fused 5-[(tert-Butoxtycarbonyl)amino]octahydroindenes as a protease activated receptor-1 (PAR1) antagonist. AB - Protease activated receptor 1 (PAR1) has been considered as a promising antiplatelet target to prevent thrombotic cardiovascular events in patients with prior myocardial infarction or peripheral arterial diseases. Previously, we found a series of octahydroindene analogues to have high potency on PAR1 and no significant cytotoxicity but poor metabolic stability in human and rat liver microsomes. We designed and synthesized substituted analogues of octahydroindenes at C5 or C6 aiming to improvement of metabolic stability, and identified that trans-fused 5-[(tert-butoxtycarbonyl)amino]octahydroindene analogues showed improved metabolic stability with maintaining good activity on PAR1. Especially, 2-methanesulfonate 57 (IC50 = 0.006 MUM; R50 = 126.3 min in human, 83.3 min in rat), sulfamate 58 (IC50 = 0.020 MUM; R50 = 52.8 min in human, 106.0 min in rat), and N-(cyclopropyl)methylsufonamide 63 (IC50 = 0.010 MUM; R50 = 51.4 min in human, 90.5 min in rat) exhibited excellent activity and metabolic stability both on human and rat liver microsomes, comparable to those obtained for varapaxar (IC50 = 0.0015 MUM; R50 = 83.2 min in human, 32.4 min in rat). Additionally, these compounds (57, 58, and 63) represented significant efficacy (IC50 = 0.0022, 0.0062, and 0.015 MUM, each) in human washed platelet aggregation (WPA) assay without cytotoxicity and CYP3A4 inhibitory activity. PMID- 27406141 TI - Exploration of acetanilide derivatives of 1-(omega-phenoxyalkyl)uracils as novel inhibitors of Hepatitis C Virus replication. AB - Hepatitis C Virus (HCV) is a major public health problem worldwide. While highly efficacious directly-acting antiviral agents have been developed in recent years, their high costs and relative inaccessibility make their use limited. Here, we describe new 1-(omega-phenoxyalkyl)uracils bearing acetanilide fragment in 3 position of pyrimidine ring as potential antiviral drugs against HCV. Using a combination of various biochemical assays and in vitro virus infection and replication models, we show that our compounds are able to significantly reduce viral genomic replication, independently of virus genotype, with their IC50 values in the nanomolar range. We also demonstrate that our compounds can block de novo RNA synthesis and that effect is dependent on a chemical structure of the compounds. A detailed structure-activity relationship revealed that the most active compounds were the N(3)-substituted uracil derivatives containing 6-(4 bromophenoxy)hexyl or 8-(4-bromophenoxy)octyl fragment at N(1) position. PMID- 27406143 TI - Trichosporon loubieri Fungemia in a 39-Year-Old Caucasian Woman With B-Cell Lymphoblastic Leukemia. AB - We report a case of Trichosporon loubieri (T. loubieri) fungemia with likely liver involvement in a 39-year-old Caucasian patient with relapsed B-cell acute lymphoblastic leukemia after an allogeneic hematopoietic cell transplant. This is the fifth published case of T. loubieri infection and only the third case of T. loubieri fungemia, to our knowledge. All 3 cases of T. loubieri infection with fungemia had liver involvement. PMID- 27406142 TI - Ischaemic preconditioning does not alter the determinants of endurance running performance in the heat. AB - PURPOSE: Ischaemic preconditioning (IP) has been shown to be ergogenic for endurance performance in normothermic conditions and alleviate physiological strain under hypoxia, potentially through haemodynamic and/or metabolic mechanisms. Exertional hyperthermia is characterised by competition for blood flow between the muscles and skin, an enhanced metabolic strain and impaired endurance performance. This study investigated the effect of IP on the determinants of endurance performance, through an incremental exercise test in the heat. METHOD: Eleven males completed two graded exercise tests in the heat (32 degrees C, 62 % RH) until volitional exhaustion, preceded by IP (4 * 5 min 220 mmHg bilateral upper leg occlusion) or a control (CON) condition (4 * 5-min 50 mmHg bilateral). RESULT: IP did not improve running speeds at fixed blood lactate concentrations of 2 and 4 mMol L(-1) (p = 0.828), or affect blood glucose concentration throughout the trial [mean (+/-SD); CON 5.03 (0.94) mMol L(-1), IP 5.47 (1.38) mMol L(-1), p = 0.260). There was no difference in [Formula: see text]O2max [CON 55.5 (3.7) mL kg(-1) min(-1), IP 56.0 (2.6) mL kg(-1) min(-1), p = 0.436], average running economy [CON 222.3 (18.0) mL kg(-1) km(-1), IP 218.9 (16.5) mL kg(-1) km(-1), p = 0.125], or total running time during graded exercise [CON 347 (42) s, IP 379 (68) s, p = 0.166]. The IP procedure did not change muscle temperature [CON ? = 0.55 (0.57) degrees C, IP ? = 0.78 (0.85) degrees C, p = 0.568], but did reduce T CORE during exercise (~-0.1 degrees C, p = 0.001). CONCLUSION: The novel application of IP prior to exercise in the heat does not enhance the determinants of endurance performance. For events where IP appears ergogenic, muscle warming strategies are unnecessary as IP does not influence deep muscle temperature. PMID- 27406147 TI - About the Journal. PMID- 27406144 TI - Folate Insufficiency Due to Celiac Disease in a 49-Year-Old Woman of Southeast Asian-Indian Ethnicity. AB - The clinical presentation of celiac disease has evolved from chronic diarrhea and malnutrition to mild nutrient insufficiencies. Recently diagnosed adults with celiac disease should be assessed for micronutrient deficiencies because early institution of a gluten-free diet (GFD) prevents morbidity and reduces the incidence of gastrointestinal malignant neoplasms and osteoporosis. In this report, we present the case of a 49-year-old woman of Southeast Asian-Indian descent living in the United States who had folate insufficiency, as manifested by low serum and red blood cell (RBC) folate levels. Further investigation, including serologic testing and intestinal biopsy, confirmed a diagnosis of celiac disease and other nutrient deficiencies. Managing the condition of this patient with folate supplements and implementation of a recommended GFD reversed the folate insufficiency. In conclusion, when serum and/or RBC levels are low in a person of Southeast Asian-Indian descent living in a country with folate fortification of the grain supply, such as the United States, the medical team needs to look for an organic cause, as in our patient, to diagnose and manage celiac disease early and, hopefully, forestall complications. PMID- 27406148 TI - Study of worker's exposure to Tantalum-bearing particles in a mining and metallurgical plant. AB - The objective of this study was to assess worker exposure to mineral dust particles, and a metabolic model, based on the model adopted by ICRP, was applied to assess human exposure to Ta, and predicted values of Ta concentrations in excreta. The occupational exposure to Th, U, Nb, and Ta-bearing particles during routine tasks to obtain Fe-Nb alloys was estimated using air samplers and excreta samples. Ta concentrations in food samples and in drinking water were also determined. The results support that workers were occupationally exposed to Ta bearing particles, and also indicate that a source of Ta exposure for both workers and the control group was the ingestion of drinking water containing soluble compounds of Ta. Therefore, some Ta compounds should be considered soluble compounds in gastrointestinal tract. Consequently, the metabolic model based on ICRP metabolic model and/or the transfer factor f 1 for Ta should be reviewed and the solubility of Ta compounds in gastrointestinal should be determined. PMID- 27406149 TI - The Association of Parental Coping and Childhood Injury. AB - Objectives Injuries are the leading cause of pediatric morbidity and mortality in the United States. Interaction between child, parent and environmental factors may contribute to injuries. This study investigates the association between coping with parenthood and injuries in children age 0-5 years. Methods In this cross-sectional observational study, we analyzed data from the 2007 National Survey of Children's Health, a random-digit-dialing, nationally-representative telephone survey. Information was obtained from a caregiver about children 5 years of age or younger. Parental coping with the demands of parenthood was categorized into three groups-"very well", "somewhat well" and "not very well" or "not very well at all". Injury was defined as caregiver report of any injury within the previous 12 months that required medical attention. Results This study included 27,471 surveys about children 5 years of age or younger. With weighted analysis, 10.4 % of children were reported to have an injury; 31.1 % of caregivers reported coping with parenthood "somewhat well" and 1.7 % reported coping "not very well"/"not very well at all". The adjusted odds ratio of sustaining an injury was 1.26 (95 % CI 1.00, 1.59) for children of parents who reported coping somewhat well with the demands of parenthood compared to those with parents coping very well. Conclusions Parental report of coping with parenthood less than very well was associated with injury in children ages 0-5 years, further highlighting the importance of the interaction between parent factors and childhood injury. PMID- 27406150 TI - Maternal Child and Family Health Nurses: Delivering a Unique Nursing Speciality. AB - Introduction This study aimed to describe Maternal Child and Family Health Nurses' (MCaFHNs) perception of their role across Australia. MCaFHNs deliver services to positively influence the growth and development of children in the early years. Little is known about their role as they deliver care to children and families in Australia. Methods This study used in-depth qualitative inquiry. Sixteen expert MCaFHNs from the eight jurisdictions in Australia took part in semi-structured interviews conducted from April 2013 to August 2013. The data were transcribed verbatim, validated by participants, and analysed thematically. Results The results indicated that the MCaFHNs' role is embedded in the principles of primary health care under an umbrella of universal service delivery with increasing overall complexity. Health promotion and early intervention are key components of the role, with services focused heavily on child growth and development and maternal mental health. Delivery of services by MCaFHNs was enriched by specific approaches to care, such as working in partnership with families, and all aspects of the role were enabled by essential specialist skills and knowledge. Discussion While role descriptors, educational backgrounds and experiences vary, participants overwhelmingly report similarities in practice. This study identified tangible reasons for the development of a nationally consistent role and practice in Australia, enabling consistency and equity of best models of practice. Such a description is essential to enable transferability and comparison with nurses working in similar contexts internationally. PMID- 27406151 TI - Household Food Insecurity Is Not Associated with Overall Diet Quality Among Pregnant Women in NHANES 1999-2008. AB - OBJECTIVE: Analyze the association between household food security status and diet quality during pregnancy. METHODS: Cross-sectional analysis of pregnant women from the National Health and Nutrition Examination Survey from 1999 to 2008. Of the 1158 pregnant women with complete household food security information, we analyzed 688 women who had complete dietary information and household incomes <=300 % of the Federal Poverty Level (FPL). Diet quality was measured by the Alternate Healthy Eating Index modified for Pregnancy (AHEI-P) from 1 to 2 24 h dietary recalls. Multivariate linear and logistic regression models were implemented to assess the association between household food security status and AHEI-P, adjusting for age, nativity, marital status, race/ethnicity, education, and household income. RESULTS: Among women with household incomes <=300 % of the FPL, 19 % were food insecure and 4 % were marginally food secure. The mean AHEI-P score was 41.9 (95 % CI 40.4, 43.3). Household food insecurity was not associated with overall diet quality. However, living in a food insecure household compared to a food secure household was associated with a 2.3 (1.3, 4.1) greater odds of having a calcium component score greater than the median intake of calcium scores among food secure women in the sample. CONCLUSIONS FOR PRACTICE: In a nationally representative sample of pregnant women, 80 % lived in a fully food secure household. Improving household food security during pregnancy is a public health opportunity to improve health outcomes; however household food security status may not be associated with overall diet quality. PMID- 27406152 TI - Geographic Accessibility to Health Services and Neonatal Mortality Among Very-Low Birthweight Infants in South Carolina. AB - Introduction Mortality for infants born with very-low birthweight (VLBW, 500-1499 grams) is markedly higher than for babies born with normal birthweight (2500-4000 grams). Although these high-risk infants show better outcomes in advanced care settings, only 80 % of VLBW infants born in South Carolina (SC) are delivered in hospitals with a level-III neonatal intensive care unit (NICU). The purpose of this research project was to assess geographic access to delivery hospitals and risk of neonatal death among singleton VLBW infants born in SC. Methods The linked birth and death records of a cross-sectional, population-based study of singleton VLBW infants born in SC between 2010 and 2012 were used (n = 2030). We assessed the impact of travel time from maternal residence to delivery hospital. Logistic regression modeling was performed with adjustments for maternal, newborn, and hospital characteristics. Results The neonatal mortality rate among singleton VLBW infants was 11.03 deaths per 100 live births in 2010-2012. We did not find a significant association between travel time to delivery hospital and neonatal mortality after adjusting for confounders. However, we found that a 1 week increase in gestational age (odds ratio (OR): 0.61) and non-Hispanic black mothers (versus non-Hispanic white mothers) (OR: 0.68) were associated with lower odds of neonatal death, whereas non-NICU admission at birth (OR: 5.90) was associated with increased odds of death. The results of the sensitivity analyses including both singleton and multiple births did not yield significant results for travel time and neonatal mortality in VLBW infants. Discussion Although we found no significant association between travel time and neonatal mortality in singleton VLBW births in SC, we identified significant factors consistent with those found in previous studies that may affect neonatal mortality. PMID- 27406153 TI - Associations of Household Wealth and Individual Literacy with Prenatal Care in Ten West African Countries. AB - Objective To examine associations of household wealth and individual literacy with prenatal care in West Africa. Methods Data on women with recent births in Benin, Burkina Faso, Ghana, Guinea, Liberia, Mali, Nigeria, Niger, Senegal and Sierra Leone were obtained from 2006 to 2010 Demographic and Health Surveys (n = 58,512). Separate logistic regressions estimated associations of literacy and wealth quintiles with prenatal care, controlling for age, parity, marital status, rural/urban residence, religion, multiple births, pregnancy wantedness, and the woman's involvement in decision-making at home. Any prenatal care was defined by >=1 prenatal care visit. Adequate prenatal care was defined as at least four prenatal care visits beginning in the first trimester, at least one with a skilled provider. Results Seventy-eight percent of women had any prenatal care; 23 % had adequate care. Women who were not literate had lower odds of having any prenatal care (odds ratio, OR 0.29; 95 % confidence interval, CI 0.26-0.33) and lower odds of adequate care (OR 0.73, CI 0.68-0.78). Women in the poorest wealth quintile were substantially less likely to have any prenatal care than women in the wealthiest quintile (OR 0.24, CI 0.11-0.18), and less likely to have adequate care (OR 0.31, CI 0.27-0.35). Conclusions for Practice A substantial percentage of women in West Africa have no prenatal care. Few have adequate care. Illiteracy and poverty are important risk factors for having little or no prenatal care. Increasing education for girls, promoting culturally appropriate messages about prenatal care, and building trust in providers may increase prenatal care. PMID- 27406155 TI - Satisfaction of Discharged Nursing Home Residents. AB - The psychometric properties of The Consumer Assessment of Healthcare Providers and Systems (CAHPS(r)) Nursing Home survey: Discharged Resident Instrument (NHCAHPS-D) are examined. A random sample of 550 nursing homes was selected from across the United States and 365 agreed to participate (participation rate = 66%). From 7,020 surveys sent to discharged residents, 4,926 were returned (response rate = 70%). The psychometric properties of the resident responses and the survey items were robust. Confirmatory factor analyses model fit statistics met the criterion for good conformance. Five of the initial NHCAHPS-D instrument domains were identified (environment, care, communication and respect, autonomy, and activities), along with a sixth (transitions) added by the authors. The standardization and reliability that NHCAHPS-D provides could facilitate the same benefits we have seen in other industries for the CAHPS family of instruments (i.e., quality improvement, reimbursement, public reporting, and benchmarking) and also become an industry standard. PMID- 27406156 TI - The association between vitamin D and urinary incontinence. PMID- 27406154 TI - Improving Adolescent Health Risk Assessment: A Multi-method Pilot Study. AB - Objectives Given poor compliance by providers with adolescent health risk assessment (HRA) in primary care, we describe the development and feasibility of using a health information technology (HIT)-enhanced HRA to improve the frequency of HRAs in diverse clinical settings, asking adolescents' recall of quality of care as a primary outcome. Methods We conducted focus groups and surveys with key stakeholders (Phase I) , including adolescents, clinic staff and providers to design and implement an intervention in a practice-based research network delivering private, comprehensive HRAs via tablet (Phase II). Providers and adolescents received geo-coded community resources according to individualized risks. Following the point-of-care implementation , we collected patient-reported outcomes using post-visit quality surveys (Phase III). Patient-reported outcomes from intervention and comparison clinics were analyzed using a mixed-model, fitted separately for each survey domain. Results Stakeholders agreed upon an HIT enhanced HRA (Phase I). Twenty-two academic and community practices in north central Florida then recruited 609 diverse adolescents (14-18 years) during primary care visits over 6 months; (mean patients enrolled = 28; median = 20; range 1-116; Phase II). Adolescents receiving the intervention later reported higher receipt of confidential/private care and counseling related to emotions and relationships (adjusted scores 0.42 vs 0.08 out of 1.0, p < .01; 0.85 vs 0.57, p < .001, respectively, Phase III) than those receiving usual care. Both are important quality indicators for adolescent well-child visits. Conclusions Stakeholder input was critical to the acceptability of the HIT-enhanced HRA. Patient recruitment data indicate that the intervention was feasible in a variety of clinical settings and the pilot evaluation data indicate that the intervention may improve adolescents' perceptions of high quality care. PMID- 27406157 TI - Low preoperative selenium is associated with post-operative atrial fibrillation in patients having intermediate-risk coronary artery surgery. AB - BACKGROUND/OBJECTIVES: Post-operative atrial fibrillation (POAF) is a frequent complication of cardiac surgery. Oxidative stress and reduced antioxidant function have major roles in its development. Selenium is a key to normal antioxidant function, and levels are often low before cardiac surgery. This study investigated whether low preoperative selenium levels were associated with POAF in cardiac surgical patients. SUBJECTS/METHODS: Using the Society of Thoracic Surgeons (STS) Mortality risk score, 50 patients having primary coronary artery bypass grafts (CABG) surgery were divided into two groups: (i) low-risk group (STS ?0.5%; n=26) and (ii) intermediate-risk group (STS ?2.0%; n=24). Plasma levels of selenium, glutathione peroxidase (GPx) and malondialdehyde (MDA) were measured in all patients at anaesthetic induction, after aortic cross-clamp removal, 3 h post cardiopulmonary bypass and on post-operative days 1 and 5. Multiple logistic regression was used to assess whether selenium levels were associated with POAF development. RESULTS: Seventeen patients developed POAF (14 patients in the intermediate-risk group and 3 patients in the low-risk group). Preoperative selenium was lower in patients who developed POAF compared with those with normal sinus rhythm (0.73+/-0.16 vs 0.89+/-0.13 MUmol/l, P=0.005), and this was independently associated with POAF (PR 0.32; 95% confidence credible interval (95%cI) 0.06-0.85, P=0.016). Regardless of POAF, preoperative selenium was lower in the intermediate-risk patients than in the low-risk patients (0.77+/ 0.15 vs 0.89+/-0.14 MUmol/l; P=0.004). CONCLUSIONS: Intermediate-risk patients with low preoperative selenium levels may be at a greater risk of developing POAF following CABG. This raises the question of whether selenium supplementation in select cardiac surgical patients may reduce their POAF risk. PMID- 27406158 TI - The nutritional quality of foods carrying health-related claims in Germany, The Netherlands, Spain, Slovenia and the United Kingdom. AB - : Backgroung/Objectives:Compares the nutritional quality of pre-packaged foods carrying health-related claims with foods that do not carry health-related claims. SUBJECT/METHODS: Cross-sectional survey of pre-packaged foods available in Germany, The Netherlands, Spain, Slovenia and the United Kingdom in 2013. A total of 2034 foods were randomly sampled from three food store types (a supermarket, a neighbourhood store and a discounter). Nutritional information was taken from nutrient declarations present on food labels and assessed through a comparison of mean levels, regression analyses and the application of a nutrient profile model currently used to regulate health claims in Australia and New Zealand (Food Standards Australia New Zealand's Nutrient Profiling Scoring Criterion, FSANZ NPSC). RESULTS: Foods carrying health claims had, on average, lower levels, per 100 g, of the following nutrients, energy-29.3 kcal (P<0.05), protein-1.2 g (P<0.01), total sugars-3.1 g (P<0.05), saturated fat-2.4 g (P<0.001), and sodium-842 mg (P<0.001), and higher levels of fibre-0.8 g (P<0.001). A similar pattern was observed for foods carrying nutrition claims. Forty-three percent (confidence interval (CI) 41%, 45%) of foods passed the FSANZ NPSC, with foods carrying health claims more likely to pass (70%, CI 64%, 76%) than foods carrying nutrition claims (61%, CI 57%, 66%) or foods that did not carry either type of claim (36%, CI 34%, 38%). CONCLUSIONS: Foods carrying health related claims have marginally better nutrition profiles than those that do not carry claims; these differences would be increased if the FSANZ NPSC was used to regulate health-related claims. It is unclear whether these relatively small differences have significant impacts on health. PMID- 27406159 TI - Changes in phase angle and body composition induced by resistance training in older women. AB - BACKGROUND: Resistance training (RT) has selective effects on body composition that may counteract the deleterious effects of aging. Changes in phase angle (PhA) may serve to monitor the influence of RT in older people. OBJECTIVES: To describe the effect of RT in training, detraining and retraining on body composition, including PhA in older women. SUBJECTS/METHODS: Thirty-three older women (?60 years old) participated. The RT program was carried out over 12 weeks for each stage (training, detraining and retraining). Whole-body fat-free mass and fat mass (FM) and appendicular lean soft tissue (ALST) measurements were carried out using a dual energy X-ray absorptiometry. Bioimpedance spectroscopy was used to estimate total body water (TBW), intra (ICF) and extracellular (ECF) fluids, whole-body resistance (R) and reactance (Xc) and PhA. Upper and lower body muscle strength were also assessed. RESULTS: From baseline to after training muscle strength, ALST and PhA significantly (P<0.05) increased. In detraining, significant (P<0.05) reductions in muscle strength, TBW, ECF, ICF and PhA along with significant (P<0.05) increases in R were observed, with the greatest magnitude observed for PhA (Delta=-7.6%). From detraining to retraining a significant reduction in FM along with increases in Xc, PhA and muscle strength were observed. Although an increase was observed from detraining to retraining in PhA, the values were still lower than baseline PhA. CONCLUSIONS: In untrained older women, a RT is associated with increases in PhA, whereas detraining results in a marked decrease in PhA, and more time may be required in retraining to counteract the negative influence of absence of exercise stimulus. PMID- 27406160 TI - The association between vitamin D and urinary incontinence. PMID- 27406161 TI - Associations between company at dinner and daily diet quality in Dutch men and women from the NQplus study. AB - BACKGROUND/OBJECTIVES: Consuming the evening meal in the company of others has been associated with overall diet quality. Nevertheless, studies on the association between type of company at dinner and diet quality in adults are scarce. SUBJECTS/METHODS: Dutch men (n=895) and women (n=845) aged between 20 and 70 years, included in a population-based observational study, were studied. Dietary intake was assessed by multiple 24-h recalls (6013 recalls) to estimate the Dutch Healthy Diet index (0-80 points) representing daily diet quality. Sex specific linear mixed models adjusting for covariates were calculated. Out-of home dinners and company at dinner were strongly associated (r=0.66), and hence in additional analyses, out-of-home dinners were excluded to avoid multicollinearity. RESULTS: Among men, daily diet quality was similar when dinners were consumed in company or consumed alone, but higher when dinner was accompanied by family (mean 46.0, s.e. 0.3) than when dinner was accompanied by others (mean 42.3, s.e. 0.7; P=0.001). Adjustment for dinner location attenuated this association, but it remained significant when excluding out-of-home dinners. Among women, daily diet quality was lower when dinner was consumed in company (mean 48.9, s.e. 0.3) than when consumed alone (mean 51.1, s.e. 0.6; P<0.001). Dinners consumed in the company of family were associated with higher daily diet quality (mean 49.3, s.e. 0.4) than dinners consumed with others (mean 45.7, s.e. 0.6; P=0.001). These associations persisted when excluding out-of-home dinners. CONCLUSIONS: Only among women, dinners consumed alone as compared with dinners in company were associated with higher diet quality. In both men and women, dinners consumed with family were associated with higher diet quality as compared with dinners with others. PMID- 27406162 TI - The nutritional management of type 3c (pancreatogenic) diabetes in chronic pancreatitis. AB - Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic diabetes, refers to diabetes caused by disease of the exocrine pancreas. T3cDM is not commonly recognised by clinicians and frequently it is misclassified as T1DM, or more commonly, T2DM. T3cDM can be difficult to distinguish from T1DM and T2DM, and it often co-exists with the latter. The aim of this review is to describe T3cDM, along with its complications, diagnosis and management. We focus on the nutritional implications of T3cDM for those with chronic pancreatitis, and provide a practical guide to the nutritional management of this condition. PMID- 27406164 TI - The Goldilocks problems in regulation. PMID- 27406163 TI - Impact of weight gain on the evolution and regression of prediabetes: a quantitative analysis. AB - BACKGROUND/OBJECTIVES: The quantitative impact of weight gain on prediabetic glucose dysregulation remains unknown; only one study quantitated the impact of weight loss. We quantified the impact of weight gain on the evolution and regression of prediabetes (PDM). SUBJECTS/METHODS: In 4234 subjects without diabetes, using logistic regression analysis with a 4.8-year follow-up period, we analyzed the relationship between (1) deltaBMI (BMIfollow-up-basal) and the progression from normal glucose regulation (NGR) to PDM or diabetes, and (2) deltaBMI and the regression from PDM to NGR. RESULTS: Mean (+/-s.d.) deltaBMI was 0.17 (+/-1.3) kg/m2 in subjects with NGR and deltaBMI was positively and independently related to progression (adjusted odds ratio (ORadj) (95% CI), 1.24 (1.15-1.34), P<0.01). Mean (+/-s.d.) deltaBMI was -0.03 (+/-1.25) kg/m2 in those with PDM and deltaBMI was negatively related to the regression (ORadj, 0.72 (0.65 0.80), P<0.01). The relation of deltaBMI to the progression was significant in men (ORadj, 1.42 (1.28-1.59), P<0.01) but not in women (ORadj, 1.05 (0.94-1.19), P=0.36). Also, the negative impact of deltaBMI on the regression was significant only in men (men, ORadj, 0.65 (0.57-0.75), P<0.01; women, ORadj, 0.94 (0.77 1.14), P=0.51). CONCLUSIONS: In Japanese adults, an increase in the BMI by even 1 kg/m2 was related to 24% increase in the risk of development of PDM or diabetes in NGR subjects and was related to 28% reduction in the regression from PDM to NGR. In women, we did not note any significant impact of weight gain on the evolution or regression of PDM. PMID- 27406165 TI - Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea. AB - BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI 1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results. PMID- 27406166 TI - Dynamic Precision Phenotyping Reveals Mechanism of Crop Tolerance to Root Herbivory. AB - The western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte) is a major pest of maize (Zea mays) that is well adapted to most crop management strategies. Breeding for tolerance is a promising alternative to combat WCR but is currently constrained by a lack of physiological understanding and phenotyping tools. We developed dynamic precision phenotyping approaches using 11C with positron emission tomography, root autoradiography, and radiometabolite flux analysis to understand maize tolerance to WCR Our results reveal that WCR attack induces specific patterns of lateral root growth that are associated with a shift in auxin biosynthesis from indole-3-pyruvic acid to indole-3-acetonitrile. WCR attack also increases transport of newly synthesized amino acids to the roots, including the accumulation of Gln. Finally, the regrowth zones of WCR-attacked roots show an increase in Gln turnover, which strongly correlates with the induction of indole-3-acetonitrile-dependent auxin biosynthesis. In summary, our findings identify local changes in the auxin biosynthesis flux network as a promising marker for induced WCR tolerance. PMID- 27406167 TI - The DELLA-CONSTANS Transcription Factor Cascade Integrates Gibberellic Acid and Photoperiod Signaling to Regulate Flowering. AB - Gibberellin (GA) and photoperiod pathways have recently been demonstrated to collaboratively modulate flowering under long days (LDs). However, the molecular mechanisms underlying this collaboration remain largely unclear. In this study, we found that GA-induced expression of FLOWERING LOCUS T (FT) under LDs was dependent on CONSTANS (CO), a critical transcription factor positively involved in photoperiod signaling. Mechanistic investigation revealed that DELLA proteins, a group of crucial repressors in GA signaling, physically interacted with CO. The DELLA-CO interactions repressed the transcriptional function of CO protein. Genetic analysis demonstrated that CO acts downstream of DELLA proteins to regulate flowering. Disruption of CO rescued the earlier flowering phenotype of the gai-t6 rga-t2 rgl1-1 rgl2-1 mutant (dellap), while a gain-of-function mutation in GA INSENSITIVE (GAI, a member of the DELLA gene) repressed the earlier flowering phenotype of CO-overexpressing plants. In addition, the accumulation of DELLA proteins and mRNAs was rhythmic, and REPRESSOR OF GA1-3 protein was noticeably decreased in the long-day afternoon, a time when CO protein is abundant. Collectively, these results demonstrate that the DELLA-CO cascade inhibits CO/FT-mediated flowering under LDs, which thus provide evidence to directly integrate GA and photoperiod signaling to synergistically modulate flowering under LDs. PMID- 27406168 TI - Stomatal Spacing Safeguards Stomatal Dynamics by Facilitating Guard Cell Ion Transport Independent of the Epidermal Solute Reservoir. AB - Stomata enable gaseous exchange between the interior of the leaf and the atmosphere through the stomatal pore. Control of the pore aperture depends on osmotic solute accumulation by, and its loss from the guard cells surrounding the pore. Stomata in most plants are separated by at least one epidermal cell, and this spacing is thought to enhance stomatal function, although there are several genera that exhibit stomata in clusters. We made use of Arabidopsis (Arabidopsis thaliana) stomatal patterning mutants to explore the impact of clustering on guard cell dynamics, gas exchange, and ion transport of guard cells. These studies showed that stomatal clustering in the Arabidopsis too many mouths (tmm1) mutant suppressed stomatal movements and affected CO2 assimilation and transpiration differentially between dark and light conditions and were associated with alterations in K(+) channel gating. These changes were consistent with the impaired dynamics of tmm1 stomata and were accompanied by a reduced accumulation of K(+) ions in the guard cells. Our findings underline the significance of spacing for stomatal dynamics. While stomatal spacing may be important as a reservoir for K(+) and other ions to facilitate stomatal movements, the effects on channel gating, and by inference on K(+) accumulation, cannot be explained on the basis of a reduced number of epidermal cells facilitating ion supply to the guard cells. PMID- 27406169 TI - The Low Molecular Weight Protein PsaI Stabilizes the Light-Harvesting Complex II Docking Site of Photosystem I. AB - PsaI represents one of three low molecular weight peptides of PSI. Targeted inactivation of the plastid PsaI gene in Nicotiana tabacum has no measurable effect on photosynthetic electron transport around PSI or on accumulation of proteins involved in photosynthesis. Instead, the lack of PsaI destabilizes the association of PsaL and PsaH to PSI, both forming the light-harvesting complex (LHC)II docking site of PSI. These alterations at the LHCII binding site surprisingly did not prevent state transition but led to an increased incidence of PSI-LHCII complexes, coinciding with an elevated phosphorylation level of the LHCII under normal growth light conditions. Remarkably, LHCII was rapidly phosphorylated in DeltapsaI in darkness even after illumination with far-red light. We found that this dark phosphorylation also occurs in previously described mutants impaired in PSI function or state transition. A prompt shift of the plastoquinone (PQ) pool into a more reduced redox state in the dark caused an enhanced LHCII phosphorylation in DeltapsaI Since the redox status of the PQ pool is functionally connected to a series of physiological, biochemical, and gene expression reactions, we propose that the shift of mutant plants into state 2 in darkness represents a compensatory and/or protective metabolic mechanism. This involves an increased reduction and/or reduced oxidation of the PQ pool, presumably to sustain a balanced excitation of both photosystems upon the onset of light. PMID- 27406170 TI - Long-Term Growth of Moss in Microfluidic Devices Enables Subcellular Studies in Development. AB - Key developmental processes that occur on the subcellular and cellular level or occur in occluded tissues are difficult to access, let alone image and analyze. Recently, culturing living samples within polydimethylsiloxane (PDMS) microfluidic devices has facilitated the study of hard-to-reach developmental events. Here, we show that an early diverging land plant, Physcomitrella patens, can be continuously cultured within PDMS microfluidic chambers. Because the PDMS chambers are bonded to a coverslip, it is possible to image P. patens development at high resolution over long time periods. Using PDMS chambers, we report that wild-type protonemal tissue grows at the same rate as previously reported for growth on solid medium. Using long-term imaging, we highlight key developmental events, demonstrate compatibility with high-resolution confocal microscopy, and obtain growth rates for a slow-growing mutant. By coupling the powerful genetic tools available to P. patens with long-term growth and imaging provided by PDMS microfluidic chambers, we demonstrate the capability to study cellular and subcellular developmental events in plants directly and in real time. PMID- 27406172 TI - Within-group relationships and lack of social enhancement during object manipulation in captive Goffin's cockatoos (Cacatua goffiniana). AB - Different types of social relationships can influence individual learning strategies in structured groups of animals. Studies on a number of avian species have suggested that local and/or stimulus enhancement are important ingredients of the respective species' exploration modes. Our aim was to identify the role of enhancement during object manipulation in different social contexts. We used focal observations to identify a linear dominance hierarchy as well as affiliative relationships between individuals in a group of 14 Goffin's cockatoos (Cacatua goffiniana, formerly goffini). Thereafter, in an unrewarded object choice task, several pairs of subjects were tested for a possible influence of social enhancement (local vs. stimulus) in three conditions: dominance, affiliation, and kinship. Our results suggest strong individual biases. Whereas previous studies on ravens and kea had indicated that enhancement in a non-food related task was influenced by the social relationship between a demonstrator and an observer (affiliated - nonaffiliated), we found no such effects in our study group. In this context, Goffin's cockatoos' object learning seems to take place more on an individual level, despite their generally high motivation to manipulate nonfood items. PMID- 27406171 TI - A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells. AB - Thousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionarily conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD-an abundant and highly conserved cytoplasmic lncRNA. Here we show that most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two mammalian Pumilio homologues. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA-binding proteins, an activity which positions them at key junctions of cellular signalling pathways. PMID- 27406173 TI - Instrument Development in Choice Experiments. Commentary on: "Applying a Framework for Instrument Development of a Choice Experiment to Measure Treatment Preferences in Type 2 Diabetes". PMID- 27406174 TI - Predictors and consequences of long-term pregnancy-related pelvic girdle pain: a longitudinal follow-up study. AB - BACKGROUND: Pelvic girdle pain (PGP) is a multifactorial condition, which can be mentally and physically compromising both during and after pregnancy. However, long-term pregnancy-related PGP has been poorly investigated. This longitudinal follow-up study uniquely aimed to describe prevalence and predictors of PGP and its consequences on women's health and function up to 11 years after pregnancy. METHODS/DESIGN: A postal questionnaire was sent to 530 women who participated in 1 of 3 randomized controlled studies for PGP in pregnancy. Women who reported experiencing lumbopelvic pain were offered a clinical examination. Main outcome measure was the presence of long term PGP as assessed by an independent examiner. Secondary outcomes were: working hours/week, function (the Disability Rating Index, and Oswestry Disability Index), self-efficacy (the General Self-Efficacy Scale), HRQL (Euro-Qol 5D and EQ-Visual scale), anxiety and depression, (Hospital anxiety and depression scale,) and pain-catastrophizing (Pain Catastrophizing Scale), in women with PGP compared to women with no PGP. RESULTS: A total of 371/530 (70 %) women responded and 37/ 371 (10 %) were classified with long-term PGP. Pregnancy-related predictors for long-term PGP were number of positive pain provocation tests (OR = 1.79), history of low back pain (LBP) (OR = 2.28), positive symphysis pressure test (OR = 2.01), positive Faber (Patrick's) test (OR = 2.22), and positive modified Trendelenburg test (OR = 2.20). Women with PGP had significantly decreased ability to perform daily activities (p < .001), lower self-efficacy (p = 0.046), decreased HRQL (p < .001), higher levels of anxiety and depression (p < .001), were more prone to pain catastrophizing, and worked significantly fewer hours/week (p = 0.032) compared to women with no PGP. CONCLUSIONS: This unique long-term follow up of PGP highlights the importance of assessment of pain in the lumbopelvic area early in pregnancy and postpartum in order to identify women with risk of long term pain. One of 10 women with PGP in pregnancy has severe consequences up to 11 years later. They could be identified by number of positive pain provocation tests and experience of previous LBP. Access to evidence based treatments are important for individual and socioeconomic reasons. PMID- 27406175 TI - Prediction of stone-free status and complication rates after tubeless percutaneous nephrolithotomy: a comparative and retrospective study using three stone-scoring systems and preoperative parameters. AB - PURPOSE: To investigate the factors predictive of surgical outcomes of tubeless percutaneous nephrolithotomy (TPCNL) and to compare the predictability and accuracy of the Guy's stone score, S.T.O.N.E. nephrolithometry, and CROES nomogram. PATIENTS AND METHODS: We reviewed retrospectively the surgical outcomes recorded consecutively and imaging data of preoperative computed tomography scans of 141 patients who had undergone TPCNL from June 2012 to October 2015. Guy's, S.T.O.N.E., and CROES stone-scoring systems (SSSs) and other prognostic factors were assessed using univariate and multivariate statistical analyses. RESULTS: The initial stone-free and complication rates after TPCNL were 78.7 (111/141) and 17.0 % (24/141). On univariate analysis, all three scoring systems were identified as significant factors in terms of stone-free rate (SFR). The multivariate logistic regression analysis showed that the Guy's stone score and stone burden >=385 mm2 had significant correlations with stone-free status [odds ratios (OR) = 3.220, p = 0.001 and OR = 6.451, p = 0.002, respectively]. Guy's stone score (OR = 1.879, p = 0.013) was an independent risk factor for the development of complications. The area under the receiver operating characteristic (ROC) curves for the Guy's, S.T.O.N.E., and CROES SSSs and stone burden showed good results (0.821, 0.816, 0.820, and 0.800, respectively). Pairwise comparison of ROC curves showed that there was no significant difference between each final score and stone burden. CONCLUSIONS: Of the three scoring systems, Guy's stone score was the only significant predictive factor for SFR and complication rates after TPCNL in the multivariate logistic regression analysis. Stone burden was significantly associated with a postoperative stone-free status (SFS). PMID- 27406176 TI - Subclinical growth of an arteriovenous fistula associated with renal biopsy: a case report. AB - BACKGROUND: Renal biopsy is not free from complications and patients who undergo this procedure are usually hospitalized to receive intensive care for several days after biopsy. In contrast, after this period, routine follow-up to detect biopsy-associated complications is rarely scheduled, unless the patient develops a clinical manifestation. We describe a case of marked enlargement of arteriovenous fistula in the kidney that occurred many years after renal biopsy. In contrast to the previous cases requiring interventional radiology, our patient showed subclinical growth of fistula over about nine years. CASE PRESENTATION: A 24-year-old man with a history of percutaneous renal biopsy was hospitalized for interventional radiology. Gross hematuria emerged shortly after biopsy, but completely disappeared with administration of hemostatic agents and bed rest. Subsequently, the patient had few symptoms for many years. A giant fistula (a gourd-shaped mass, size 26 * 22 and 12 * 11 mm) was unexpectedly detected by ultrasonography performed for examination of an unrelated disorder (slight elevation of serum transaminase) at 9 years after the original biopsy. The fistula was successfully treated with radiological intervention. Thus, subclinical development of complications associated with renal biopsy should be considered, even in an uneventful course. CONCLUSIONS: This case provides a platform to discuss the importance of long-term follow-up of patients after renal biopsy despite of its difficulty. PMID- 27406177 TI - Initial outcomes of a harmonized approach to collect welfare data in sport and leisure horses. AB - A truthful snapshot of horse welfare conditions is a prerequisite for predicting the impact of any actions intended to improve the quality of life of horses. This can be achieved when welfare information, gathered by different assessors in diverse geographical areas, is valid, comparable and collected in a harmonized way. This paper aims to present the first outcomes of the Animal Welfare Indicators (AWIN) approach: the results of on-farm assessment and a reliable and harmonized data collection system. A total of 355 sport and leisure horses, stabled in 40 facilities in Italy and in Germany, were evaluated by three trained assessors using the AWIN welfare assessment protocol for horses. The AWINHorse app was used to collect, store and send data to a common server. Identified welfare issues were obesity, unsatisfactory box dimensions, long periods of confinement and lack of social interaction. The digitalized data collection was feasible in an on-farm environment, and our results suggest that this approach could prove useful in identifying the most relevant welfare issues of horses in Europe or worldwide. PMID- 27406178 TI - Optimizing the Dopant and Carrier Concentration of Ca5Al2Sb6 for High Thermoelectric Efficiency. AB - The effects of doping on the transport properties of Ca5Al2Sb6 are investigated using first-principles electronic structure methods and Boltzmann transport theory. The calculated results show that a maximum ZT value of 1.45 is achieved with an optimum carrier concentration at 1000 K. However, experimental studies have shown that the maximum ZT value is no more than 1 at 1000 K. By comparing the calculated Seebeck coefficient with experimental values, we find that the low dopant solubility in this material is not conductive to achieve the optimum carrier concentration, leading a smaller experimental value of the maximum ZT. Interestingly, the calculated dopant formation energies suggest that optimum carrier concentrations can be achieved when the dopants and Sb atoms have similar electronic configurations. Therefore, it might be possible to achieve a maximum ZT value of 1.45 at 1000 K with suitable dopants. These results provide a valuable theoretical guidance for the synthesis of high-performance bulk thermoelectric materials through dopants optimization. PMID- 27406179 TI - A cross-sectional study of the availability and price of anti-malarial medicines and malaria rapid diagnostic tests in private sector retail drug outlets in rural Western Kenya, 2013. AB - BACKGROUND: Although anti-malarial medicines are free in Kenyan public health facilities, patients often seek treatment from private sector retail drug outlets. In mid-2010, the Affordable Medicines Facility-malaria (AMFm) was introduced to make quality-assured artemisinin-based combination therapy (ACT) accessible and affordable in private and public sectors. METHODS: Private sector retail drug outlets stocking anti-malarial medications within a surveillance area of approximately 220,000 people in a malaria perennial high-transmission area in rural western Kenya were identified via a census in September 2013. A cross sectional study was conducted in September-October 2013 to determine availability and price of anti-malarial medicines and malaria rapid diagnostic tests (RDTs) in drug outlets. A standardized questionnaire was administered to collect drug outlet and personnel characteristics and availability and price of anti-malarials and RDTs. RESULTS: Of 181 drug outlets identified, 179 (99 %) participated in the survey. Thirteen percent were registered pharmacies, 25 % informal drug shops, 46 % general shops, 13 % homesteads and 2 % other. One hundred sixty-five (92 %) had at least one ACT type: 162 (91 %) had recommended first-line artemether lumefantrine (AL), 22 (12 %) had recommended second-line dihydroartemisinin piperaquine (DHA-PPQ), 85 (48 %) had sulfadoxine-pyrimethamine (SP), 60 (34 %) had any quinine (QN) formulation, and 14 (8 %) had amodiaquine (AQ) monotherapy. The mean price (range) of an adult treatment course for AL was $1.01 ($0.35 4.71); DHA-PPQ was $4.39 ($0.71-7.06); QN tablets were $2.24 ($0.12-4.71); SP was $0.62 ($0.24-2.35); AQ monotherapy was $0.42 ($0.24-1.06). The mean AL price with or without the AMFm logo did not differ significantly ($1.01 and 1.07, respectively; p = 0.45). Only 17 (10 %) drug outlets had RDTs; 149 (84 %) never stocked RDTs. The mean RDT price was $0.92 ($0.24-2.35). CONCLUSIONS: Most outlets never stocked RDTs; therefore, testing prior to treatment was unlikely for customers seeking treatment in the private retail sector. The recommended first-line treatment, AL, was widely available. Although SP and AQ monotherapy are not recommended for treatment, both were less expensive than AL, which might have caused preferential use by customers. Interventions that create community demand for malaria diagnostic testing prior to treatment and that increase RDT availability should be encouraged. PMID- 27406180 TI - Clinical features in patients with positional obstructive sleep apnea according to its subtypes. AB - PURPOSE: This study aimed to determine the prevalence of positional obstructive sleep apnea (OSA) and its subtypes in Korean adults with newly diagnosed OSA and document the clinical characteristics of positional OSA and its subtypes compared to non-positional OSA METHODS: In this cross-sectional study, we evaluated 1052 OSA adults. Positional OSA was defined as an overall apnea-hypopnea index (AHI) >=5 and supine AHI to non-supine AHI ratio of >=2. Positional OSA was subtyped depending on the degree of AHI while in the non-supine position: subtype I (a non supine AHI <5/h), subtype II (a non-supine AHI >=5/h and <15/h), and subtype III (a non-supine AHI >=15/h). To compare clinical characteristics between patient groups depending on the positional tendency of OSA, statistical analyses were performed. RESULTS: The prevalence of positional OSA was 75.6 % with 39.9 % having AHI normalized <5/h while in non-supine position. Positional OSA patients had milder OSA, older age, and lower BMI than did non-positional OSA patients. However, having positional OSA did not influence daytime sleepiness, depressive symptoms, anxiety, and health-related quality of life. Unlike the subtype I and II positional OSAs, subtype III did not differ in clinical features from non positional OSA. There were significant differences in supine sleep time depending on the positional tendency of OSA. Subtype III positional OSA had the shortest supine sleep time whereas subtype I positional OSA and non-positional OSA had the longest supine sleep time. CONCLUSIONS: Positional OSA subtypes have different clinical characteristics. Subtyping of positional OSA is helpful for developing specific treatment strategies according to positional tendency. PMID- 27406181 TI - Effect of CPAP on cardiovascular risks in OSA patients. A 4-year follow-up, preliminary data. PMID- 27406182 TI - Rethinking the service delivery system of psychological interventions in low and middle income countries. AB - BACKGROUND: Global mental health is a growing field intricately connected to broader health, violence and economic issues. Despite the high prevalence and cost of mental health disorders, an estimated 75 % of those with need in lower resource settings do not receive intervention. Most studies to date have examined the effectiveness of single-disorder mental health treatments - an approach that may be a significant challenge to scale-up and sustainability in lower resource settings. MAIN BODY: This paper presents a brief overview of the scientific progress in global mental health, and suggests consideration of an internal stepped care delivery approach. An internal stepped care model is one idea of a delivery system, utilizing a common elements approach, where the same provider could navigate between different elements based on severity and type of problems of the client. It is distinct from traditional stepped care models in that clients remain with the same provider, rather than relying on referral systems. CONCLUSION: An internal stepped care delivery system based on a simplified common elements approach could be more efficient, scalable, sustainable, and reduce the loss of clients to referrals in lower resource settings. PMID- 27406183 TI - Cardiac amyloidosis: still challenging. PMID- 27406185 TI - Mucopolysaccharidosis I; Parental beliefs about the impact of disease on the quality of life of their children. AB - BACKGROUND: Hematopoietic stem cell transplants, alongside enzyme replacement therapy and good multi-disciplinary care, have dramatically improved the life expectancy in children with Mucopolysaccharidosis (MPS) I, with better objective and functional outcomes. Despite these improvements, children with both the attenuated (non-Hurler) and severe (Hurler) variants of the disease have marked residual morbidity. Children with MPS I suffer with head and neck disease including obstructive sleep apnoea and hearing loss. The impact of these on quality of life has been poorly researched and no previous work has been published looking at patients' perception of their own health, an important domain when considering the impact of treatment. METHODS: This exploratory qualitative study aimed to discover the effect of head and neck disease, alongside that of MPS I as a whole, on the quality of life of affected children. A grounded theory approach was used to conduct this study. Children and their parents were invited to participate in semi-structured interviews. The transcribed interviews were coded and emergent themes explored until saturation occurred. RESULTS: The families of eleven children with MPS I were interviewed, five with Hurler's and six with the attenuated non-Hurler's. Important themes to emerge were- the fear of dying associated with obstructive sleep apnoea, difficulties communicating at school due to the delayed acquisition of language, chronic pain and restricted mobility, physical differences and restricted participation in social activities such as sports secondary to the musculoskeletal disease burden. The overall theme running through the analysis was the desire to fit in with ones peers. CONCLUSION: Parents and children with MPS 1 worry about 'fitting-in' with broader society. The presence of airway disease has a profound impact on the emotional well being of parents whilst language delay and musculoskeletal disease have the biggest impact on the quality of life of the children themselves. It is important to understand the impact of MPS I on the quality of life of children and their families so that we may improve future treatment and management of this sub-group of children who have an increasing life span. PMID- 27406186 TI - Defining and Controlling Exposure During In Vitro Toxicity Testing and the Potential of Passive Dosing. AB - Toxicity testing using in vitro bioassays is assuming an increasingly important role. Nevertheless, several issues remain with regard to their proper application, which mainly relate to the proper definition and control of the test chemical(s) concentrations to which the cells or tissues are exposed. This has fundamental implications for understanding the underlying relationship between the in vitro exposure regime and response, and leads to uncertainty in the resulting bioassay data. This chapter covers the definition and control of exposure of hydrophobic organic chemicals (HOCs) in in vitro bioassays aimed at measuring their toxicity. A review of the fate of HOCs in typical in vitro set ups is followed by a discussion of how to define the test exposure. Currently applied approaches for introducing HOCs into in vitro bioassays are then related to these different definitions of test exposure. Finally, passive dosing as one possible approach for giving defined and constant dissolved concentrations of HOCs in in vitro toxicity tests is introduced, using examples taken from the literature, and how this might be better integrated into high throughput in vitro toxicity testing is discussed. PMID- 27406184 TI - Interventional procedures and future drug therapy for hypertension. AB - Hypertension management poses a major challenge to clinicians globally once non drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID- 27406187 TI - The ontology of medically related social entities: recent developments. AB - BACKGROUND: The Ontology of Medically Related Social Entities (OMRSE) was initially developed in 2011 to provide a framework for modeling demographic data in Resource Description Framework/Web Ontology Language. It is built upon the Basic Formal Ontology and conforms to Open Biomedical Ontologies Foundry's best practices. DESCRIPTION: We report recent development of OMRSE which includes representations of organizations, roles, facilities, demographic data, enrollment in insurance plans, and data about socio-economic indicators. CONCLUSIONS: OMRSE's coverage has been expanding in recent years to include a wide variety of classes and has been useful in several biomedical applications. PMID- 27406188 TI - Liver mobilization and liver hanging for totally laparoscopic right hepatectomy: an easy way to do it. AB - PURPOSE: The purpose of this study is to describe a technical modification that facilitates right liver mobilization in laparoscopic right hepatectomy (LRH). METHODS: In the supine position, an inflatable device is placed under the patient's right chest. For right hemiliver mobilization, the table is placed in 30 degrees anti-Trendelenburg and full-left tilt. Balloon inflation offers an additional 30 degrees left inclination that places the patient in an almost left lateral position. Foot and lateral supports are placed to prevent patient slippage during changes in the patient positioning. RESULTS: From December 2013 to October 2015, this technique has been used in 10 consecutive LRH. The indications for these procedures were as follows: four donor hepatectomies for living donor liver transplant, three hepatocellular carcinomas and one peripheral cholangiocarcinoma in cirrhotic patients, one hepatocellular carcinoma in a non cirrhotic patient, and one case of colorectal cancer metastases. In this period, it has also been used to facilitate mobilization and resection in the posterior segments of the liver in seven patients. In every case, right hemiliver mobilization was easily performed in a maximum time of 15 min and placement of a tape or plastic tube for liver hanging was prepared. We have not observed any complication directly attributable to the technique herein described (i.e. right brachialgia; arms, back or left flank pain) in the early or late postoperative follow-up. CONCLUSIONS: The additional left inclination obtained with the inflation of a balloon under the right chest facilitates right hemiliver mobilization. Its use may help in the performance and adoption of LRH. PMID- 27406190 TI - Staphylococcus aureus Pore-Forming Toxins. AB - Staphylococcus aureus (S. aureus) is a formidable foe equipped with an armamentarium of virulence factors to thwart host defenses and establish a successful infection. Among these virulence factors, S. aureus produces several potent secreted proteins that act as cytotoxins, predominant among them the beta barrel pore-forming toxins. These toxins play several roles in pathogenesis, including disruption of cellular adherens junctions at epithelial barriers, alteration of intracellular signaling events, modulation of host immune responses, and killing of eukaryotic immune and non-immune cells. This chapter provides an updated overview on the S. aureus beta-barrel pore-forming cytotoxins, the identification of toxin receptors on host cells, and their roles in pathogenesis. PMID- 27406189 TI - Tackling Threats and Future Problems of Multidrug-Resistant Bacteria. AB - With the advent of the antibiotic era, the overuse and inappropriate consumption and application of antibiotics have driven the rapid emergence of multidrug resistant pathogens. Antimicrobial resistance increases the morbidity, mortality, length of hospitalization and healthcare costs. Among Gram-positive bacteria, Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) Mycobacterium tuberculosis, and among the Gram-negative bacteria, extended-spectrum beta lactamase (ESBLs)-producing bacteria have become a major global healthcare problem in the 21st century. The pressure to use antibiotics guarantees that the spread and prevalence of these as well as of future emerging multidrug-resistant pathogens will be a persistent phenomenon. The unfeasibility of reversing antimicrobial resistance back towards susceptibility and the critical need to treat bacterial infection in modern medicine have burdened researchers and pharmaceutical companies to develop new antimicrobials effective against these difficult-to-treat multidrug-resistant pathogens. However, it can be anticipated that antibiotic resistance will continue to develop more rapidly than new agents to treat these infections become available and a better understanding of the molecular, evolutionary and ecological mechanisms governing the spread of antibiotic resistance is needed. The only way to curb the current crisis of antimicrobial resistance will be to develop entirely novel strategies to fight these pathogens such as combining antimicrobial drugs with other agents that counteract and obstruct the antibiotic resistant mechanisms expressed by the pathogen. Furthermore, as many antibiotics are often inappropriately prescribed, a more personalized approach based on precise diagnosis tools will ensure that proper treatments can be promptly applied leading to more targeted and effective therapies. However, in more general terms, also the overall use and release of antibiotics in the environment needs to be better controlled. PMID- 27406191 TI - University closes PTSD studies after complaints from drug regulator. PMID- 27406195 TI - An Unconditional Test for Change Point Detection in Binary Sequences with Applications to Clinical Registries. AB - OBJECTIVES: Methods for change point (also sometimes referred to as threshold or breakpoint) detection in binary sequences are not new and were introduced as early as 1955. Much of the research in this area has focussed on asymptotic and exact conditional methods. Here we develop an exact unconditional test. METHODS: An unconditional exact test is developed which assumes the total number of events as random instead of conditioning on the number of observed events. The new test is shown to be uniformly more powerful than Worsley's exact conditional test and means for its efficient numerical calculations are given. Adaptions of methods by Berger and Boos are made to deal with the issue that the unknown event probability imposes a nuisance parameter. The methods are compared in a Monte Carlo simulation study and applied to a cohort of patients undergoing traumatic orthopaedic surgery involving external fixators where a change in pin site infections is investigated. RESULTS: The unconditional test controls the type I error rate at the nominal level and is uniformly more powerful than (or to be more precise uniformly at least as powerful as) Worsley's exact conditional test which is very conservative for small sample sizes. In the application a beneficial effect associated with the introduction of a new treatment procedure for pin site care could be revealed. CONCLUSIONS: We consider the new test an effective and easy to use exact test which is recommended in small sample size change point problems in binary sequences. PMID- 27406196 TI - An Association between Low Levels of Dietary Protein, Elevated NPY Gene Expression in the Basomedial Hypothalamus and Increased Food Intake. AB - We sought to extend our previous observation that low dietary protein could increase the gene expression of neuropeptide Y (NPY) in the basomedial hypothalamus. To better define the relationship between the level of dietary protein, NPY gene expression, and food intake, we examined the effect of 5 isocaloric diets, each containing a different level of dietary protein (5%, 10%, 15%, 20%, 35% casein). Test diets were fed for 11 days. Food intakes and body weights were monitored throughout. Total RNA was isolated from the basomedial hypothalamus and a dot blot analysis was performed to determine NPY mRNA levels. A body composition analysis was also performed. The average daily food intake was increased by about 20% in rats fed the 5% casein diet. These rats also had an increase in NPY gene expression. Body weight gain was severely attenuated due mainly to a decrease in body water, but also to a decrease in body protein. However, total body fat was increased such that there was no effect on total body energy content. These results suggest that low dietary protein can increase the capacity for NPY synthesis in the hypothalamus and that this may lead to an increase in food intake. PMID- 27406197 TI - Neuropeptide Y in the Ventromedial and Suprachiasmatic Nuclei: Role in the Feeding Pattern of Monosodium Glutamate-Treated Rats. AB - Neuropeptide Y (NPY) is an important mediator for the light/dark cycle entrainment of circadian rhythms including feeding rhythm. It is present in the main circadian oscillator, the suprachiasmatic nucleus which receives NPY efferences from the intergeniculate leaflet to form a pathway named the geniculo hypothalamic tract (GHT). In the present experiment, we measured NPY in the arcuate nucleus (ARC) and in areas more or less related to feeding rhythm regulation in rats with brain lesion induced by monosodium glutamate (MSG). Newborn Long-Evans rats were subcutaneously injected three times during the first week of life either with MSG (4 mg/g BW; n = 15) or with saline (n = 10). One week after weaning, food intake and NPY concentrations in the GHT, ventromedial (VMN) and dorsomedial nuclei and lateral hypothalamus were measured. Daily food intake in the MSG-treated rats was slightly lower than in control (saline) rats (10.8 +/- 0.3 vs 11.9 +/- 0.4 g; p < 0.03). This diminution in food intake was only observed during the dark period (p < 0.02). NPY in the ARC rats was 50% lower in MSG-treated rats than in control rats (p < 0.001) confirming therefore the neurotoxicity of the neonatal injections of high doses of MSG. A smaller decrease was observed in the VMN of MSG-treated rats (-30%; p < 0.02) whereas no variations were observed in the GHT and in the other areas. We conclude that when the GHT is intact, gross regulation of feeding rhythm is maintained. The VMN might contribute to the slight change in the dark/light distribution of food intake through the NPY variation. PMID- 27406198 TI - Neurochemical and Hormonal Changes in Lean and Obese Zucker Rats During 48 Hours of Calorie Deprivation. Are They related? AB - Lean and obese Zucker rats were deprived of food for 12, 24, and 48 h. After sacrifice, plasma and brain tissue were saved for hormone and regional hypothalamic monoamine analysis. An ad libitum group was killed at time 0 for comparison to the food deprived groups. Insulin (I), C-peptide (CP), glucose, and the CP/I ratio were dramatically different across phenotype. Glucagon was only different at 12 h of caloric deprivation. Insulin secretion dropped substantially with fasting as reflected by the decrease in C-peptide plasma levels in both lean and obese rats. The CP/I ratio, which indicates clearance of insulin, increased in lean rats across time of fasting but did not significantly change in obese rats. Several distinct changes occurred between phenotypes in the hypothalamus across food deprivation. Lateral hypothalamic 5HT content and 5HT turnover (5HIAA/5HT) increased in lean but not obese rats during the period of fasting. Likewise ventromedial hypothalamic dopamine turnover (NE/DA) decreased during caloric deprivation in lean rats but not in the obese rats. This same turnover was increased in the PVNA of obese but not lean rats during caloric deprivation. Individual measurements of both C-peptide and insulin correlated significantly with LH 5HT turnover and VMH dopamine turnover in lean rats but not obese rats. These data suggest that obese rat's hypothalami may possibly be insensitive to insulin or some factor such as leptin that insulin may regulate. Because obese rats cannot change their levels of hypothalamic neurotransmitters when insulin or some other insulin induced factor changes, may suggest clues as to why these rats became obese. Perhaps these data may help explain the altered body weight set point, increased adiposity, and hyperphagia in these animals. PMID- 27406199 TI - Dietary Antioxidant Deficiency Facilitates Cortical Spreading Depression Induced by Photoactivated Riboflavin. AB - It is known that the photoactivation of riboflavin produces superoxide radicals. We investigated the ability of this process to elicit spreading depression (SD) in the cerebral cortex of adult rats receiving either a normal diet (control group; n = 9) or fed a diet free from vitamins C and E during 4-6 weeks prior to the experiment (deficient group; n = 15). SD was initially elicited, at 20 min intervals, by 2% KC1 topically applied for 1 min to a point (2-3 mm in diameter) on the dura mater at the frontal cortex and SD propagation was monitored by both EEG and DC-recordings at two points of the parietal region. After a 1-2 h "baseline" recording of KCl-elicited SD, tests were performed with 1.0 mM riboflavin applied to the same frontal region and illuminated by a white light bulb (40 W, 10-15 cm from the cortical surface, for 1-3 min). In the control group, 37 applications of riboflavin + light were performed (average: 4.1 applications per rat; range: 3-7) and 11 of these applications (29.7%) elicited SD in 7 out of the 9 rats. In the deficient group, the effectiveness of photoactivated riboflavin to elicit SD increased significantly to 62.8% (44 out of 70 applications; 15 out of 15 rats; average: 4.7 applications per rat; range: 3-6; P < 0.05). Elicitation of SD was not obtained, either by illumination of an equivalent volume of Ringer solution applied to the same region, or by riboflavin applied without illumination. The results demonstrate that photoactivated riboflavin is capable of eliciting SD in the rat cerebral cortex, and that dietary deficiency of the antioxidant vitamins C and E can enhance brain susceptibility to this process. PMID- 27406200 TI - Effects of Noise-Induced Arousal on Chewing of Sweet Food and the Subjective Motivation to Eat. AB - The effects of noise-induced arousal on chewing, subjective motivation to eat, the pleasantness of sweet food, and food intake were investigated. Twenty-four healthy normal weight male subjects received cookies differing in sucrose content (2%, 11%, 18% or 27%) before, during, and after 10 min of intermittent white noise. Half of the subjects were exposed to high-level noise (95 dB(A)) to induce psychological arousal. The remaining other half were exposed to low-level noise (60 dB(A)) as a control condition. During noise exposure the high-level noise group exhibited a shorter chewing time and fewer overall chewing movements with cookies of a medium sucrose content (11% or 18%). After exposure, subjects who received the high-level noise reported a reduced desire to eat, and tended to consume less strawberry ice cream. No significant effect of noise and Noise * Sugar interaction could be detected from taste and pleasantness ratings. The findings point to a relation between arousal, hunger motivation and chewing behavior. PMID- 27406201 TI - Place Learning Impairment in Chronically Tryptophan-Restricted Rats. AB - Acute pharmacological studies have shown that the relationship between serotonin and place learning is very unclear and when serotoninergic neurotransmission is manipulated, little or no effect on place learning has been observed. Since tryptophan is the precursor of the serotonin synthesis, female rats were chronically given a tryptophan-restricted diet from the time they were weaned until they were 60 days old and their place learning ability was assessed in the Morris' water maze, during the dark phase and under red lighting. Animals should have solved two 5 attempt blocks separated by a change in diametral position of the goal, at 21, 40 and 60 days of age. Experimental animals took longer distances than control animals, mainly in the second attempt block both at 40 and 60 days of age. Also, a remarkable irregularity on place learning curves of experimental animals was seen, possibly due to an apparent loss of maze solving strategy. These animals were also incapable of efficiently adjusting their external signals-related cognitive map when the goal was moved to a different position and, on the other hand, two different patterns were seen in maze solving at 60 days of age in these same animals. These findings strongly suggest that indirect lowering of brain serotonin levels through chronic restriction of dietary tryptophan may be responsible for the spatial learning deficits observed. PMID- 27406202 TI - Dendritic Spine Density of Pyramidal Neurons in Field CA1 of the Hippocampus Decreases due to Chronic Tryptophan Restriction. AB - The CA1 hippocampal region is involved in organizing several neuropsychological processes. Pyramidal cell dendritic spines in the CA1 field of rats subjected to chronic tryptophan diet restriction were quantified at 21, 40, and 60 days of age. At 40 days of age, the number of spines in the distal third of the apical dendrite was smaller in experimental animais. The same was true for the medial third of the apical dendrite and the basal dendrite at 60 days of age. The results could be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the hippocampal Ammon's horn and, particularly, on the CA1 pyramidal neurons as well as on aferences to the hippocampus. Since the present is a model of generalized tryptophan restriction, neurochemical studies are needed to dilucidate this hypothesis. PMID- 27406203 TI - Plasma Amino Acids in Children under Two Years of Age with Severe Undernutrition. Increase of Taurine in Kwashiorkor. AB - There are many reports documenting modifications of different plasma components in undenutrition, including the protein-calorie (marasmus) or the protein deficiency (kwashiorkor) subtypes. However, there is no detailed study on the effect of undernutrition on plasma amino acid pattern during the first two years of life, a critical period of biological development in humans. The plasma concentrations of 19 amino acids were analysed in 32 children under two years of age presenting severe undernutrition: marasmus, kwashiorkor or mixed picture. The subjects were admitted to the hospital as inpatients and received a balanced diet as the only treatment. Samples of venous blood were taken from nine patients at discharge and plasma amino acid profile was compared with the preadmission profile. A healthy control group included 11 children visiting the hospital for regular pediatric examination. At the time of admission the amino acid levels of tyrosine, tryptophan and leucine were significantly lower in the undernourished group of children compared to controls. On the other hand, levels of aspartate were higher in the children with malnutrition. These changes in amino acids were not present at the time of discharge from hospital after diet therapy. Taurine concentration was higher in undernourished children and remained high at the time of discharge. Compared with the control group, marasmic children showed increases in plasma aspartic acid and serine, and decrease in trypthophan. Kwashiorkor children had lower levels of tyrosine, trypthophan and leucine, but higher levels of taurine. The elevation of taurine was not corrected by diet therapy. PMID- 27406204 TI - Prolonged Stimulation of Corticosterone Secretion by Corticotropin-Releasing Hormone in Rats Exhibiting High Preference for Dietary Fat. AB - Through the secretion of corticosterone, the hypothalamo-pituitary-adrenal (HPA) axis is thought to play an important role in the regulation of caloric intake and dietary fat preference. In an earlier study, we demonstrated a positive correlation between urinary corticosterone output and dietary fat preference. Furthermore, dietary fat preference was augmented following chronic but not acute hypercorticosteronemia produced by exogenous corticosterone administration. These observations led us to explore whether the HPA axis of rats exhibiting high preference for fat may have exaggerated sensitivity to corticotropinreleasing hormone (CRH). The results of these studies show a delayed and blunted but more prolonged corticosterone response to CRH in the fat-preferring rats compared with that of the carbohydrate-preferring rats. PMID- 27406205 TI - Authors' reply to Kole. PMID- 27406206 TI - A novel pattern of leaf movement: the case of Capparis spinosa L. AB - A novel type of heliotropic leaf movement is presented for Capparis spinosa L., a summer perennial shrub of Mediterranean and arid ecosystems. In contrast to plants that demonstrate uniform diaheliotropic and/or paraheliotropic movement for all their foliage, the alternate leaves of C. spinosa follow different movement patterns according to their stem azimuth and the side of the stem that they come from (cluster). Additionally, leaf movement for each cluster may not be uniform throughout the day, showing diaheliotropic characteristics during half of the day and paraheliotropic characteristics during the rest of the day. In an attempt to reveal the adaptive significance of this differential movement pattern, the following hypotheses were tested: (i) increase of the intercepted solar radiation and photosynthesis, (ii) avoidance of photoinhibitory conditions, (iii) amelioration of water-use efficiency and (iv) adjustment of the leaf temperature microenvironment. No evidence was found in support of the first two hypotheses. A slight difference toward a better water use was found for the moving compared with immobilized leaves, in combination with a better cooling effect. PMID- 27406207 TI - Investigating the causality of changes in the landscape pattern of Lake Urmia basin, Iran using remote sensing and time series analysis. AB - Lake Urmia is the second largest hypersaline lake in the world in terms of surface area. In recent decades, the drop in water level of the lake has been one of the most important environmental issues in Iran. At present, the entire basin is threatened due to abrupt decline of the lake's water level and the consequent increase in salinity. Despite the numerous studies, there is still an ambiguity about the main cause of this environmental crisis. This paper is an attempt to detect the changes in the landscape structure of the main elements of the whole basin using remote sensing techniques and analyze the results against climate data with time series analysis for the purpose of achieving a more clarified illustration of processes and trends. Trend analysis of the different affecting factors indicates that the main cause of the drastic dry out of the lake is the huge expansion of irrigated agriculture in the basin between 1999 and 2014. The climatological parameters including precipitation and temperature cannot be the main reasons for reduced water level in the lake. The results show how the increase in irrigated agricultural area without considering the water resources limits can lead to a regional disaster. The approach used in this study can be a useful tool to monitor and assess the causality of environmental disaster. PMID- 27406208 TI - Think regionally, act locally: metals in honeybee workers in the Netherlands (surveillance study 2008). AB - In June 2008, a surveillance study for metals in honeybees was performed in the Netherlands. Randomly, 150 apiaries were selected. In each apiary, five colonies were sampled. Per apiary, the hive samples were pooled. The apiary sample was analysed for Al, As, Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, Sb, Se, Sn, Sr, Ti, V and Zn. All metals could be detected in all apiaries. As, Li, Sb, Sn and V were detected in part of the apiaries. The overall picture showed a regional pattern. In apiaries in the east of the Netherlands, Al, Ba, Cr, Mn, Mo, Ni, Se and Ti are found in higher concentrations compared to the west. In-region variation was demonstrated, indicating local effects. The vicinity of the apiaries was mapped afterwards and characterised as land uses of >50 % agricultural area, >50 % wooded area, >50 % urban area and mixed land use within a circle of 28 km(2) around the apiary. The results indicated that in apiaries located in >50 % wooded areas, significantly higher concentrations of Al, Ba, Cd, Cr, Cu, Li, Mn, Mo, Ni, Sb, Sr, Ti and Zn were found compared to agricultural, urban and mixed land use areas. We conclude that (1) the ratio between metal concentrations varies per region, demonstrating spatial differences, and (2) there is in-region local variation per metal. The results indicate the impact of land use on metal concentrations in honeybees. For qualitative bioindication studies, regional, local and land use effects should be taken into account. PMID- 27406209 TI - Assessment of methane generation, oxidation, and emission in a subtropical landfill test cell. AB - This paper presents results of a methane balance assessment in a test cell built in a region with a subtropical climate near Sao Paulo, Brazil. Measurements and calculations were carried out to obtain the total methane emission to the atmosphere, the methane oxidation rate in the cover, and the total methane generation rate in the test cell. The oxidation rate was obtained through a calculation scheme based on a vertical one-dimensional methane transport in the cover region. The measured maximum and mean methane fluxes to the atmosphere were 124.4 and 15.87 g m(-2) d(-1), respectively. The total methane generation rate obtained for the test cell was 0.0380 +/- 0.0075 mol s(-1). The results yielded that 69 % of the emitted methane occurred through the central well and 31 % through the cover interface with the atmosphere. The evaluations of the methane oxidation fraction for localized conditions in the lateral embankment of the test cell yielded 0.36 +/- 0.11, while for the whole test cell yielded 0.15 +/- 0.10. These results conciliate localized and overall evaluations reported in the literature. The specific methane generation rate obtained for the municipal solid waste with an age of 410 days was 317 +/- 62 mol year(-1) ton(-1). This result from the subtropical Sao Paulo region is lower than reported figures for tropical climates and higher than reported figures for temperate climates. PMID- 27406210 TI - Asymmetrical seeding of MSCs into fibrin-poly(ester-urethane) scaffolds and its effect on mechanically induced chondrogenesis. AB - Mesenchymal stem cells (MSCs) are currently being investigated as candidate cells for regenerative medicine approaches for the repair of damaged articular cartilage. For these cells to be used clinically, it is important to understand how they will react to the complex loading environment of a joint in vivo. In addition to investigating alternative cell sources, it is also important for the structure of tissue-engineered constructs and the organization of cells within them to be developed and, if possible, improved. A custom built bioreactor was used to expose human MSCs to a combination of shear and compression loading. The MSCs were either evenly distributed throughout fibrin-poly(ester-urethane) scaffolds or asymmetrically seeded with a small proportion seeded on the surface of the scaffold. The effect of cell distribution on the production and deposition of cartilage-like matrix in response to mechanical load mimicking in vivo joint loading was then investigated. The results show that asymmetrically seeding the scaffold led to markedly improved tissue development based on histologically detectable matrix deposition. Consideration of cell location, therefore, is an important aspect in the development of regenerative medicine approaches for cartilage repair. This is particularly relevant when considering the natural biomechanical environment of the joint in vivo and patient rehabilitation protocols. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406211 TI - Enhanced P-selectin expression on platelet-a marker of platelet activation, in young patients with angiographically proven coronary artery disease. AB - P-selectin (CD62p) exposure is an established marker for platelet activation. P selectin exposure can trigger variety of thrombotic and inflammatory reactions. In patients with coronary artery disease (CAD), platelets are activated, and hence, there is increased P-selectin exposure. The role of P-selectin exposure in patients on treatment with statins and anti-platelets is conflicting. A case control study was performed to determine P-selectin exposure in consecutively recruited 142 patients (age <= 55 years) with angiographically proven CAD on treatment and 92 asymptomatic controls. P-selectin exposure was determined by flow cytometry. Data on conventional risk factors were obtained along with estimation of levels of thrombotic [fibrinogen, lipoprotein (a), tissue plasminogen activator, plasminogen activator inhibitor-1, homocysteine and von Willebrand factor] and anti-thrombotic factors (antithrombin III). The P-selectin exposure was compared among patient groups who had different modes of presentation of CAD and categories of CAD disease severity. The patients were followed up for a period of 26 months. The results indicate that P-selectin exposure was significantly elevated in patients (mean +/- SD 9.24 +/- 11.81) compared to controls (mean +/- SD 1.48 +/- 2.85) with p < 0.0001. Similarly, conventional risk factors were significantly elevated in patients. P-selectin exposure showed significant negative correlation with antithrombin III levels. P selectin exposure was higher in patients who presented with acute coronary syndromes than those who presented with effort angina. Cardiovascular event rate was 6 % on follow-up. The study establishes that thrombotic-inflammatory pathways enhancing P-selectin exposure unrelated to treatment might be activated in patients, while the event rate remained lowered, and hence, treatment strategies should be inclusive to control these factors. PMID- 27406212 TI - Magnesium Status and Its Association with Oxidative Stress in Obese Women. AB - The aim of this study was to assess the relationship between magnesium status and oxidative stress in obese and nonobese women. This cross-sectional study included 83 women, aged between 20 and 50 years, who were divided into two groups: the obese group (n = 31) and the control group (n = 52). The control group was age matched with the obese group. Magnesium intake was monitored using 3-day food records and NutWin software version 1.5. The plasma and erythrocyte magnesium concentrations were determined by flame atomic absorption spectrophotometry. Plasma levels of thiobarbituric acid reactive substances (TBARS) were determined as biomarkers for lipid peroxidation and therefore of oxidative stress. The mean values of the magnesium content in the diet were found to be lower than those recommended, though there was no significant difference between groups (p > 0.05). The mean concentrations of plasma and erythrocyte magnesium were within the normal range, with no significant difference between groups (p > 0.05). The mean concentration of plasma TBARS was higher in obese woman, and the difference between the groups was statistically different (p < 0.05). There was a positive correlation between erythrocyte magnesium and plasma TBARS in the obese group (p = 0.021). Obese patients ingest low dietary magnesium content, which does not seem to affect the plasma and erythrocyte concentrations of the mineral. The study showed a negative correlation between erythrocyte magnesium concentrations and plasma TBARS, suggesting the influence of magnesium status on the parameters of oxidative stress in obese women. PMID- 27406213 TI - Regional hypoxic cerebral vasodilation facilitated by diameter changes primarily in anterior versus posterior circulation. AB - The inability to quantify cerebral blood flow and changes in macrocirculation cross-sectional area in all brain regions impedes robust insight into hypoxic cerebral blood flow control. We applied four-dimensional flow magnetic resonance imaging to quantify cerebral blood flow (ml * min-1) and cross-sectional area (mm2) simultaneously in 11 arteries. In healthy adults, blood pressure, O2 Saturation (SpO2), and end-tidal CO2 were measured at baseline and steady-state hypoxia (FiO2 = 0.11). We investigated left and right: internal carotid, vertebral, middle, anterior, posterior cerebral arteries, and basilar artery. Hypoxia (SpO2 = 80+/-2%) increased total cerebral blood flow from 621+/-38 to 742+/-50 ml * min-1 ( p < 0.05). Hypoxia increased cerebral blood flow, except in the right posterior cerebral arteries. Hypoxia increased cross-sectional area in the anterior arteries (left and right internal carotid arteries, left and right middle, p < 0.05; left and right anterior p = 0.08) but only the right vertebral artery of the posterior circulation. Nonetheless, relative cerebral blood flow distribution and vascular reactivity (Delta%cerebral blood flow * DeltaSpO2-1) were not different between arteries. Collectively, moderate hypoxia: (1) increased cerebral blood flow, but relative distribution remains similar to normoxia, (2) evokes similar vascular reactivity between 11 arteries, and (3) increased cross-sectional area primarily in the anterior arteries. This study provides the first wide-ranging, quantitative, functional and structural data regarding intracranial arteries during hypoxia in humans, highlighting cerebral blood flow regulation of microcirculation and macrocirculation differs between anterior and posterior circulation. PMID- 27406214 TI - Validating abortion procedure coding in Canadian administrative databases. AB - BACKGROUND: The British Columbia (BC) Ministry of Health collects abortion procedure data in the Medical Services Plan (MSP) physician billings database and in the hospital information Discharge Abstracts Database (DAD). Our study seeks to validate abortion procedure coding in these databases. METHODS: Two randomized controlled trials enrolled a cohort of 1031 women undergoing abortion. The researcher collected database includes both enrollment and follow up chart review data. The study cohort was linked to MSP and DAD data to identify all abortions events captured in the administrative databases. We compared clinical chart data on abortion procedures with health administrative data. We considered a match to occur if an abortion related code was found in administrative data within 30 days of the date of the same event documented in a clinical chart. RESULTS: Among 1158 abortion events performed during enrollment and follow-up period, 99.1 % were found in at least one of the administrative data sources. The sensitivities for the two databases, evaluated using a gold standard, were 97.7 % (95 % confidence interval (CI): 96.6-98.5) for the MSP database and 91.9 % (95 % CI: 90.0-93.4) for the DAD. CONCLUSIONS: Abortion events coded in the BC health administrative databases are highly accurate. Single-payer health administrative databases at the provincial level in Canada have the potential to offer valid data reflecting abortion events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01174225 , Current Controlled Trials ISRCTN19506752 . PMID- 27406215 TI - Why several truths can be true. AB - In this paper, we offer a perspective on complementarity, acknowledging that it is not possible for human perception and cognition to grasp reality with unambiguous concepts or theories. Therefore, multiple concepts and perspectives are valid when they are not exaggerated beyond reasonable limits and do not claim exclusive validity. We recommend a humble stance enabling respectful dialogue between different perspectives in medical science and practice. KEY POINTS No single perspective in clinical or scientific medicine can exhaustively explain medical phenomena. Scientific attitude is characterised by a willingness to look for objections against what we prefer as truths. Complementarity or unifying contradictions are concepts that allow for humility and pluralism in clinical and scientific medicine. PMID- 27406216 TI - Development of a Full-Thickness Human Gingiva Equivalent Constructed from Immortalized Keratinocytes and Fibroblasts. AB - Organotypic models make it possible to investigate the unique properties of oral mucosa in vitro. For gingiva, the use of human primary keratinocytes (KC) and fibroblasts (Fib) is limited due to the availability and size of donor biopsies. The use of physiologically relevant immortalized cell lines would solve these problems. The aim of this study was to develop fully differentiated human gingiva equivalents (GE) constructed entirely from cell lines, to compare them with the primary cell counterpart (Prim), and to test relevance in an in vitro wound healing assay. Reconstructed gingiva epithelium on a gingiva fibroblast-populated collagen hydrogel was constructed from cell lines (keratinocytes: TERT or HPV immortalized; fibroblasts: TERT immortalized) and compared to GE-Prim and native gingiva. GE were characterized by immunohistochemical staining for proliferation (Ki67), epithelial differentiation (K10, K13), and basement membrane (collagen type IV and laminin 5). To test functionality of GE-TERT, full-thickness wounds were introduced. Reepithelialization, fibroblast repopulation of hydrogel, metabolic activity (MTT assay), and (pro-)inflammatory cytokine release (enzyme linked immunosorbent assay) were assessed during wound closure over 7 days. Significant differences in basal KC cytokine secretion (IL-1alpha, IL-18, and CXCL8) were only observed between KC-Prim and KC-HPV. When Fib-Prim and Fib-TERT were stimulated with TNF-alpha, no differences were observed regarding cytokine secretion (IL-6, CXCL8, and CCL2). GE-TERT histology, keratin, and basement membrane protein expression very closely represented native gingiva and GE-Prim. In contrast, the epithelium of GE made with HPV-immortalized KC was disorganized, showing suprabasal proliferating cells, limited keratinocyte differentiation, and the absence of basement membrane proteins. When a wound was introduced into the more physiologically relevant GE-TERT model, an immediate inflammatory response (IL-6, CCL2, and CXCL8) was observed followed by complete reepithelialization. Seven days after wounding, tissue integrity, metabolic activity, and cytokine levels had returned to the prewounded state. In conclusion, immortalized human gingiva KC and fibroblasts can be used to make physiologically relevant GE, which resemble either the healthy gingiva or a neoplastic disease model. These organotypic models will provide valuable tools to investigate oral mucosa biology and can also be used as an animal alternative for drug targeting, vaccination studies, microbial biofilm studies, and testing new therapeutics. PMID- 27406217 TI - Fucoxanthin Suppresses Lipid Accumulation and ROS Production During Differentiation in 3T3-L1 Adipocytes. AB - Fucoxanthin, a pigment from the chloroplasts of marine brown algae, has a number of effects against obesity, diabetes, inflammation and cancer and provides cerebrovascular protection. In this study, we investigated the inhibitory effects of fucoxanthin on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis. Treatment with fucoxanthin suppresses protein levels of the adipogenic transcription factors CCAAT/enhancer-binding protein alpha C/EBPalpha and peroxisome proliferator-activated receptor-gamma and of their target protein, fatty acid binding protein 4. Lipogenesis-related enzymes, such as diglyceride acyltransferase 1 and lysophosphatidic acid acyltransferase-theta, were downregulated by fucoxanthin. The ROS-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and the NADPH-generating enzyme glucose-6-phosphate dehydrogenase also decreased following fucoxanthin treatment. The adipokine adiponectin and the ROS-scavenging enzymes superoxide dismutase 2, glutathione reductase and catalase were dose-dependently increased by fucoxanthin. Furthermore, lipolysis-related enzymes and superoxide dismutase 1 were slightly decreased, because of the suppression of lipid-generating factors and the cytosolic enzyme NOX4. To confirm these results, we investigated lipid accumulation and ROS production in zebrafish, where fucoxanthin suppressed lipid and triglyceride accumulation, as well as ROS production. Our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic and lipogenic factors and ROS-regulating enzymes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406218 TI - Femoral overgrowth in children with congenital pseudarthrosis of the Tibia. AB - BACKGROUND: Having observed a tendency towards femoral overgrowth (FO) of the affected limb in children with atrophic-type congenital pseudarthrosis of the tibia (CPT), we aimed to identify the incidence of, contributors to, and patterns of FO among such children. METHODS: We retrospectively evaluated 55 children with CPT, 22 with prepseudarthrosis and 33 with atrophic-type CPT from 1989 to 2012. FO was defined as an affected femoral segment >=10 mm longer than the contralateral segment. We investigated FO incidences in prepseudarthrosis versus atrophic-type CPT. Sex, laterality, coexistence of neurofibromatosis type 1, development of frank pseudarthrosis, extent of tibial shortening, shortening in foot height, deformity severity, distraction osteogenesis (DO) treatment, refracture, increased femoral neck-shaft angle, tibiofemoral angle, and ankle valgus angle were investigated to identify potential contributors to FO. Patterns of FO were also determined. RESULTS: At initial presentation, 11 patients exhibited a mean of 13 mm (10-23) of FO. However, the nature of FO changed over time during the follow-up period (mean, 10.8 years; range, 4.3-19.3). At the last follow-up, 14 patients presented with a mean of 12 mm (10-18) of FO. With the exception of one patient, all patients with FO presented with atrophic-type CPT. Frank pseudarthrosis, DO treatment, and increased femoral neck-shaft angle were significantly associated with FO (p = 0.016, p = 0.001, and p = 0.005, respectively). Diverse patterns of FO were observed. CONCLUSIONS: FO of the affected limb is frequently encountered in patients with atrophic-type CPT. A compensatory response to frank pseudarthrosis, DO treatment, and neurofibromatosis may play a role in the diverse patterns of FO. PMID- 27406219 TI - Conundrums in neurology: diagnosing serotonin syndrome - a meta-analysis of cases. AB - BACKGROUND: Serotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. Serotonin syndrome's main feature is neuro muscular hyperexcitability, which in many cases is mild but in some cases can become life-threatening. The diagnosis of serotonin syndrome remains challenging since it can only be made on clinical grounds. Three diagnostic criteria systems, Sternbach, Radomski and Hunter classifications, are available. Here we test the validity of four assumptions that have become widely accepted: (1) The Hunter classification performs clinically better than the Sternbach and Radomski criteria; (2) in contrast to neuroleptic malignant syndrome, the onset of serotonin syndrome is usually rapid; (3) hyperthermia is a hallmark of severe serotonin syndrome; and (4) serotonin syndrome can readily be distinguished from neuroleptic malignant syndrome on clinical grounds and on the basis of medication history. METHODS: Systematic review and meta-analysis of all cases of serotonin syndrome and toxicity published between 2004 and 2014, using PubMed and Web of Science. RESULTS: Two of the four assumptions (1 and 2) are based on only one published study each and have not been independently validated. There is little agreement between current criteria systems for the diagnosis of serotonin syndrome. Although frequently thought to be the gold standard for the diagnosis of the serotonin syndrome, the Hunter criteria did not perform better than the Sternbach and Radomski criteria. Not all cases seem to be of rapid onset and only relatively few cases may present with hyperthermia. The 0 differential diagnosis between serotonin syndrome and neuroleptic malignant syndrome is not always clear cut. CONCLUSIONS: Our findings challenge four commonly made assumptions about serotonin syndrome. We propose our meta-analysis of cases (MAC) method as a new way to systematically pool and interpret anecdotal but important clinical information concerning uncommon or emergent phenomena that cannot be captured in any other way but through case reports. PMID- 27406221 TI - Psychosocial Factors and Sport Injuries: Meta-analyses for Prediction and Prevention. AB - BACKGROUND: Several studies have suggested that psychosocial variables can increase the risk of becoming injured during sport participation. OBJECTIVES: The main objectives of these meta-analyses were to examine (i) the effect sizes of relationships between the psychosocial variables (suggested as injury predictors in the model of stress and athletic injury) and injury rates, and (ii) the effects of psychological interventions aimed at reducing injury occurrence (prevention). METHODS: Electronic databases as well as specific sport and exercise psychology journals were searched. The literature review resulted in 48 published studies containing 161 effect sizes for injury prediction and seven effect sizes for injury prevention. RESULTS: The results showed that stress responses (r = 0.27, 80 % CI [0.20, 0.33]) and history of stressors (r = 0.13, 80 % CI [0.11, 0.15]) had the strongest associations with injury rates. Also, the results from the path analysis showed that the stress response mediated the relationship between history of stressors and injury rates. For injury prevention studies, all studies included (N = 7) showed decreased injury rates in the treatment groups compared to control groups. CONCLUSION: The results support the model's suggestion that psychosocial variables, as well as psychologically, based interventions, can influence injury risk among athletes. PMID- 27406222 TI - Disodium N,N-bis-(dithiocarboxy)ethanediamine: synthesis, performance, and mechanism of action toward trace ethylenediaminetetraacetic acid copper (II). AB - A new effective multi-dithiocarbamate heavy metal precipitant, disodium N,N-bis (dithiocarboxy) ethanediamine (BDE), was synthesized by mixing ethanediamine with carbon disulfide under alkaline conditions, and it was utilized for removing trace ethylenediaminetetraacetic acid copper (II) (EDTA-Cu) from wastewater. Its structure was confirmed by ultraviolet spectra, Fourier transform infrared spectra, scanning electron microscopy, thermogravimetric analysis, and elemental analysis. The removal performance of EDTA-Cu by BDE was evaluated according to BDE dosage, initial concentration, pH, and reaction time through single-factor experiments. With the optimized conditions of a pH range of 3-9, dosage ratio of BDE/Cu of 1:1, PAM dosage of 1 mg/L, and reaction time of 4 min, the removal efficiency of Cu(2+) was more than 98 % from simulated wastewater containing EDTA Cu with initial concentrations of 5-100 mg/L. Treatment of actual EDTA-Cu wastewater showed that BDE performed superior effectiveness, and the average residential concentration of Cu(2+) was 0.115 mg/L. Besides, the stability of chelated precipitate and the reaction mechanism of BDE and EDTA-Cu were also introduced. The toxicity characteristic leaching procedure (TCLP) and semi dynamic leaching test (SDLT) indicated that the chelated precipitate was non hazardous and stable in weak acid and alkaline conditions. The BDE reacts with EDTA-Cu at a stoichiometric ratio, and the removal of Cu(2+) was predominantly achieved through the replacement reaction of BDE and EDTA-Cu. PMID- 27406223 TI - In situ remediation of ortho-nitrochlorobenzene in soil by dual oxidants (hydrogen peroxide/persulfate). AB - The efficacies of catalyzed H2O2, activated persulfate, and catalyzed H2O2 persulfate processes for the degradation of ortho-nitrochlorobenzene (o-NCB) in soil were investigated. The application of catalyzed H2O2-persulfate process was promising, and after a careful adjustment of oxidants and activator doses, it demonstrated a considerable improvement in o-NCB degradation compared with activated persulfate process and catalyzed H2O2 process. The degradation of o-NCB in catalyzed H2O2-persulfate process was obviously influenced by the concentration of persulfate and H2O2, the molar ratio between persulfate and H2O2, the concentration of o-NCB, and initial pH. Degradation of o-NCB was obviously inhibited by the addition of tert-butyl alcohol, methanol, and phenol, suggesting that nitrobenzene was dominantly oxidized by HO. and SO4 (-). generated in the catalyzed H2O2-persulfate process. The results from these studies demonstrated that the natural iron species present in soil could effectively facilitate the degradation of organic pollutants in the presence of H2O2 and persulfate. PMID- 27406224 TI - Scale-up of electrolytic and photoelectrolytic processes for water reclaiming: a preliminary study. AB - This work focuses on the scale-up of electrochemical and photoelectrochemical oxidation processes with diamond anodes for the removal of organic pollutants and disinfection of treated urban wastewater, two of the most important parameters for the reclaiming of wastewater. The removal of organics was studied with actual biologically treated urban wastewater intensified with 100 mg dm(-3) of caffeine, added as a trace organic pollutant. The disinfection was also studied with biologically treated urban wastewater, and Escherichia coli was used to monitor the efficiency of the process. Results obtained with a single DiaCell(r) 101 were compared with those obtained with a single-stack DiaCell(r) 1001 and with a pilot plant made up of five of these stacks. Results obtained demonstrate that scale-up is not a simple but a very complex process, in which not only the electrode and the irradiation dose are important but also mass transfer conditions. Enhanced mass transport conditions have a determining and very positive effect on the removal of organics and a negative effect on the disinfection. Likewise, ultraviolet (UV) irradiation affects in a different way in the different setups used, having a great influence on the removal of complex organics and on the speciation of oxidants produced during disinfection. This works helps to understand the key differences observed in the scale-up, and it is a first approach for future works focused on the real application of conductive diamond electrochemical oxidation. PMID- 27406226 TI - Electrocatalytic oxidation of phenol from wastewater using Ti/SnO2-Sb2O4 electrode: chemical reaction pathway study. AB - In this study, a titanium plate was impregnated with SnO2 and Sb (Ti/SnO2-Sb2O4) for the electrocatalytic removal of phenol from wastewater, and the chemical degradation pathway was presented. The effects of various parameters such as pH, current density, supporting electrolyte, and initial phenol concentration were studied. At optimum conditions, it was found that phenol was quickly oxidized into benzoquinone because of the formation of various strong radicals during electrolysis by the Ti/SnO2-Sb2O4 anode from 100 to <1 mg/L over 1 h. The results of GC/MS analysis showed the presence of some esters of organic acid such as oxalic acid and formic acid. HPLC analysis showed only trace amounts of benzoquinone remaining in the solution. The efficiency of TOC removal at the Ti/SnO2-Sb2O4 anode surface showed a degradation rate of 49 % over 2 h. Results showed that the molecular oxygen potential at the electrode was 1.7 V. The phenol removal mechanism at the surface of the Ti/SnO2-Sb2O4 anode was influenced by the pH. Under acidic conditions, the mechanism of electron transfer occurred directly, whereas under alkaline conditions, the mechanism can be indirect. This research shows that the proposed electrolyte can significantly influence the efficiency of phenol removal. It can be concluded that the treatment using an appropriate Ti/SnO2-Sb2O4 electrode surface can result in the rapid oxidation of organic pollutants. PMID- 27406225 TI - Evaluating genotoxic risks in Brazilian public health agents occupationally exposed to pesticides: a multi-biomarker approach. AB - This is the first study demonstrating genotoxic effects and whole transcriptome analysis on community health agents (CHAs) occupationally exposed to pesticides in Central Brazil. For the transcriptome analysis, we found some genes related to Alzheimer's disease (LRP1), an insulin-like growth factor receptor (IGF2R), immunity genes (IGL family and IGJ), two genes related to inflammatory reaction (CXCL5 and CCL3), one gene related to maintenance of cellular morphology (NHS), one gene considered to be a strong apoptosis inductor (LGALS14), and several transcripts of the neuroblastoma breakpoint family (NBPF). Related to comet assay, we demonstrated a significant increase in DNA damage, measured by the olive tail moment (OTM), in the exposed group compared to the control group. Moreover, we also observed a statistically significant difference in OTM values depending on GSTM1 genotypes. Therefore, Brazilian epidemiological surveillance, an organization responsible for the assessment and management of health risks associated to pesticide exposure to CHA, needs to be more proactive and considers the implications of pesticide exposure for CHA procedures and processes. PMID- 27406227 TI - HIV Disclosure Anxiety: A Systematic Review and Theoretical Synthesis. AB - HIV disclosure can help people living with HIV to access social support, enhance antiretroviral adherence, facilitate engagement in care and reduce unprotected sex. Given interpersonal risks associated with HIV disclosure, however, anxiety about sharing one's status is common. To investigate anxiety about HIV disclosure in HIV-positive populations, we conducted a systematic review of qualitative and quantitative studies, with 119 studies included. The review demonstrated that perceived interpersonal risks are associated with HIV disclosure and outlined evidence of associations with anxiety, fear and worry. We present a new cognitive model of HIV disclosure anxiety adapted from clinical theories of health and social anxiety, consistent with evidence from the review. The model attempts to explain the development and maintenance of anxiety in individuals whose functioning is most affected by concerns about sharing their status. Implications for helping people living with HIV struggling with significant levels of anxiety about HIV disclosure are discussed. PMID- 27406228 TI - Identifying Factors Associated with Low-Adherence and Subsequent HIV Seroconversions Among South African Women Enrolled in a Biomedical Intervention Trial. AB - Sub-Saharan Africa has the highest number of HIV infected individuals in the world. Developing and implementing effective biomedical interventions still remains urgent. Poor adherence has been commonly identified as one of the major barriers for the success of HIV prevention trials. A better understanding of how to improve adherence remains a research priority. In this analysis, younger age (<35 years), number of children <=2, being single/not cohabiting and having a new partner during the study follow up were all significantly associated with poor adherence and subsequent HIV seroconversions. At population level, these three factors collectively associated with 56 % of the low level adherence and 75 % of the HIV seroconversions. Results highlighted the importance of effective adherence and comprehensive contraceptive counselling of women who enrol in HIV prevention trials. Culturally and socially appropriate methods are needed to achieve and maintain optimum adherence levels in future HIV prevention research. PMID- 27406229 TI - Erratum to: Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac outcomes after 10 years' treatment. PMID- 27406230 TI - [Prevalence and age-related changes of corneal astigmatism in patients before cataract surgery]. AB - BACKGROUND: The aim of this study was to determine the extent and the distribution of corneal astigmatism in patients awaiting cataract surgery in a mid-European tertiary clinic centre and hence to establish the demand for methods reducing corneal astigmatism. PATIENTS AND METHODS: Keratometry measurements of cataract surgery candidates assigned to a university clinic between January 2013 and October 2014 were recorded and analysed retrospectively. RESULTS: A total of 6900 eyes of 3450 patients with a mean age of 72.5 +/- 12.2 were analyzed. The corneal astigmatism was more than 0.5 dioptres (D) in 5193 eyes (75.3 %), >1.0 D in 2641 eyes (38.3 %), >1.5 D in 1304 eyes (18.9 %), >2.0 D in 644 eyes (9.3 %), >2.5 D in 363 eyes (5.3 %), >3.0 D in 236 eyes (3.4 %) and >3.5 D in 149 eyes (2.2 %). With increasing age a shift from with-the-rule astigmatism towards against-the-rule astigmatism was observed. CONCLUSION: Of the patients admitted for routine cataract surgery at our clinic, 2641 eyes (38.3 %) had an astigmatism greater than 1.0 D. Our data could be helpful in establishing a protocol for using toric intraocular lenses and to determine the costs. PMID- 27406231 TI - Influence of the chelator structures on the stability of Re and Tc tricarbonyl complexes with iminodiacetic acid tridentate ligands: a computational study. AB - The development of novel radiopharmaceuticals for nuclear medicine based on M(CO)3 (M = Tc, Re) complexes has attracted great attention. The versatility of this core and the easy production of the fac-[M(CO)3(H2O)3](+) precursor could explain this interest. The main characteristics of these tricarbonyl complexes are the high substitution stability of the three CO ligands and the corresponding lability of the coordinated water molecules, yielding, via easy exchange of a variety of bi- and tridentate ligands, complexes xof very high kinetic stability. Here, a computational study of different tricarbonyl complexes of Re(I) and Tc(I) was performed using density functional theory. The solvent effect was simulated using the polarizable continuum model. These structures were used as a starting point to investigate the relative stabilities of tricarbonyl complexes with various tridentate ligands. These complexes included an iminodiacetic acid unit for tridentate coordination to the fac-[M(CO)3](+) moiety (M = Re, Tc), an aromatic ring system bearing a functional group (-NO2, -NH2, and -Cl) as a linking site model, and a tethering moiety (a methylene, ethylene, propylene butylene, or pentylene bridge) between the linking and coordinating sites. The optimized complexes showed geometries comparable to those inferred from X-ray data. In general, the Re complexes were more stable than the corresponding Tc complexes. Furthermore, using NH2 as the functional group, a medium length carbon chain, and ortho substitution increased complex stability. All of the bonds involving the metal center presented a closed shell interaction with dative or covalent character, and the strength of these bonds decreased in the sequence Tc CO > Tc-O > Tc-N. PMID- 27406232 TI - Cost-Effectiveness of Pharmacogenomic and Pharmacogenetic Test-Guided Personalized Therapies: A Systematic Review of the Approved Active Substances for Personalized Medicine in Germany. AB - BACKGROUND: The use of targeted therapies has recently increased. Pharmacogenetic tests are a useful tool to guide patient treatment and to test a response before administering medicines. Pharmacogenetic tests can predict potential drug resistance and may be used for determining genotype-based drug dosage. However, their cost-effectiveness as a diagnostic tool is often debatable. In Germany, 47 active ingredients are currently approved. A prior predictive test is required for 39 of these and is recommended for eight. The objective of this study was to review the cost-effectiveness (CE) of pharmacogenetic test-guided drug therapy and compare the application of drugs with and without prior genetic testing. METHODS: A systematic literature review was conducted to identify the CE and cost utility of genetic tests. Studies from January 2000 until November 2015 were searched in 16 databases including Medline, Embase, and Cochrane. A quality assessment of the full-text publications was performed using the validated Quality of Health Economic Studies (QHES) instrument. RESULTS: In the majority of the included studies, the pharmacogenetic test-guided therapy represents a cost effective/cost-saving treatment option. Only seven studies lacked a clear statement of CE or cost-savings, because of uncertainty, restriction to specific patient populations, or assumptions for comparative therapy. Moreover, the high quality of the available evidence was evaluated. CONCLUSION: Pharmacogenetic testing constitutes an opportunity to improve the CE of pharmacotherapy. The CE of targeted therapies depends on various factors including costs, prevalence of biomarkers, and test sensitivity and specificity. To guarantee the CE comparability of stratified drug therapies, national and international standards for evaluation studies should be defined. PMID- 27406234 TI - Australian researchers declare an end to AIDS as a public health issue. PMID- 27406233 TI - Evaluation and clinical significance of cyclin-dependent kinase5 expression in cervical lesions: a clinical research study in Guangxi, China. AB - BACKGROUND: Studies have been reported that cyclin-dependent kinase5 (CDK5) was associated with the development of several cancers. However, the relationship between CDK5 level and clinicopathological factors is still poorly understood in cervical diseases. The aim of the current study was to investigate the expression of CDK5 and its clinical significance in variant cervical lesions. METHODS: Immunohistochemistry (IHC) was used to detect CDK5 expression in 54 cases of chronic cervicitis, 42 cases of condyloma acuminate (CA), 38 cases of carcinoma in situ, and 360 cases of cervical cancers [adenocarcinoma, n = 63; squamous cell carcinoma (SCC), n = 263; adenosquamous carcinoma, n = 34]. The clinicopathological characteristics in relation to CDK5 were examined by Pearson's Chi-square test. RESULTS: The positive rates of CDK5 were 27.8, 31.0, 50, 54.0, 58.8, and 62.7 % in chronic cervicitis, CA, carcinoma in situ, adenocarcinoma, adenosquamous carcinoma and SCC, respectively. Statistically analysis showed that CDK5 expression in cervical cancer tissues was higher than non-cervical cancer tissues (inflammation and CA) (P < 0.001). The overexpression of CDK5 was significantly correlated with lymph node metastasis (r = 0.317; P < 0.001), histological type (r = 0.198; P < 0.001), FIGO stage (r = 0.358; P < 0.001), TNM stage (r = 0.329; P < 0.001) and pathological grade (r = 0.259; P < 0.001) in cervical lesions evaluated by Pearson's Chi-square test. Furthermore, the positive relationships were found between CDK5 and lymph node metastasis (P < 0.001), FIGO stage (P < 0.001), TNM stage (P < 0.001) and pathological grade (P < 0.001) in SCC. CDK5 was positively interrelated to TNM stage (P = 0.017) in adenosquamous carcinoma. CONCLUSIONS: CDK5 may play a vital role in the development of cervical cancer, which may be a marker for the diagnosis, therapy and prognosis of cervical cancer. PMID- 27406235 TI - Decomposing socio-economic inequalities in leisure-time physical inactivity: the case of Spanish children. AB - BACKGROUND: Physical inactivity is associated with an increased risk of all-cause mortality and entails a substantial economic burden for health systems. Also, the analysis of inequality in lifestyles for young populations may contribute to reduce health inequalities during adulthood. This paper examines the income related inequality regarding leisure-time physical inactivity in Spanish children. METHODS: In this cross-sectional study based on the Spanish National Health Survey for 2011-12, concentration indices are estimated to measure socioeconomic inequalities in leisure-time physical inactivity. A decomposition analysis is performed to determine the factors that explain income-related inequalities. RESULTS: There is a significant socioeconomic gradient favouring the better-off associated with leisure-time physical inactivity amongst Spanish children, which is more pronounced in the case of girls. Income shows the highest contribution to total inequality, followed by education of the head of the household. The contribution of several factors (education, place of residence, age) significantly differs by gender. CONCLUSIONS: There is an important inequity in the distribution of leisure-time physical inactivity. Public policies aimed at promoting physical activity for children should prioritize the action into the most disadvantaged subgroups of the population. As the influence of determinants of health styles significantly differ by gender, this study points out the need of addressing the research on income-related inequalities in health habits from a gender perspective. PMID- 27406236 TI - Syndromic inherited poikiloderma due to a de novo mutation in FAM111B. PMID- 27406237 TI - Patients' Perspectives on Information and Communication About Sexual and Relational Issues in Rheumatology Health Care. AB - INTRODUCTION: Men and women with rheumatic diseases report a significantly negative impact on multiple areas of life, including sexuality. Research indicates that patients want to discuss sexual issues with health professionals (HPs) in rheumatology care but these issues are rarely addressed in consultations. AIM: The objective of the present study was to explore patients' experiences of communication with HPs about disease-related sexual issues, their perceptions of the relevance of these issues in rheumatology care and their preferences for how these topics should be handled. METHODS: A qualitative design was used and 18 semi-structured interviews were performed, including eight women and ten men with inflammatory rheumatic joint diseases, aged 29-62 years. The interviews were recorded and transcribed verbatim. Data were analysed thematically. RESULTS: Four main themes were derived from the interviews: (i) relevance of sexual issues; (ii) vital conditions for communication; (iii) individual preferences in mode and timing of information and communication; and (iv) benefits of information and communication. The participants expressed that, although sexual issues are relevant, necessary conditions for good communication are largely lacking. HPs' knowledge, experience and personal skills, as well as having sufficient time were essential. HPs lack of initiating sexual topics contributed to uncertainty about whether their sexual challenges were disease related and whether it was a legitimate topic to discuss in rheumatology care. CONCLUSION: Patients wanted HPs to possess knowledge about possible disease related challenges in sexual life and intimate relationships, and to facilitate communication about these aspects. There is a need to develop practice guidelines to enable HPs to integrate sexual issues as an aspect of healthcare delivery in a patient-friendly manner. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406239 TI - Facile synthesis of hybrid CNTs/NiCo2S4 composite for high performance supercapacitors. AB - In this work, a novel carbon nanotubes (CNTs)/NiCo2S4 composite for high performance supercapacitors was prepared via a simple chemical bath deposition combined with a post-anion exchange reaction. The morphologies and phase structures of the composites were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy (Raman), X-ray photoelectron spectroscopy (XPS) and low-temperature sorption of nitrogen (BET). The electro-chemical tests revealed that the CNT/NiCo2S4 composite exhibited high electrochemical performance, because the CNTs were used as a conductive network for the NiCo2S4 hexagonal nanoplates. Compared with pure NiCo2S4 and the mechanically mixed CNTs/NiCo2S4 composite, the CNTs/NiCo2S4 composite electrode material exhibited excellent supercapacitive performance, such as a high specific capacitance up to 1537 F/g (discharge current density of 1 A/g) and an outstanding rate capability of 78.1% retention as the discharge current density increased to 100 A/g. It is therefore expected to be a promising alternative material in the area of energy storage. PMID- 27406238 TI - ENPP1 processes protein ADP-ribosylation in vitro. AB - ADP-ribosylation is a conserved post-translational protein modification that plays a role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of ADP-ribosylation is linked to the physiopathology of several human diseases including cancers, diabetes and neurodegenerative disorders. Protein ADP ribosylation can be reversed by the macrodomain-containing proteins PARG, TARG1, MacroD1 and MacroD2, which hydrolyse the ester bond known to link proteins to ADP ribose as well as consecutive ADP-ribose subunits; targeting this bond can thus result in the complete removal of the protein modification or the conversion of poly(ADP-ribose) to mono(ADP-ribose). Recently, proteins containing the NUDIX domain - namely human NUDT16 and bacterial RppH - have been shown to process in vitro protein ADP-ribosylation through an alternative mechanism, converting it into protein-conjugated ribose-5'-phosphate (R5P, also known as pR). Though this protein modification was recently identified in mammalian tissues, its physiological relevance and the mechanism of generating protein phosphoribosylation are currently unknown. Here, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) as the first known mammalian enzyme lacking a NUDIX domain to generate pR from ADP-ribose on modified proteins in vitro. Thus, our data show that at least two enzyme families - Nudix and ENPP/NPP - are able to metabolize protein-conjugated ADP-ribose to pR in vitro, suggesting that pR exists and may be conserved from bacteria to mammals. We also demonstrate the utility of ENPP1 for converting protein-conjugated mono(ADP-ribose) and poly(ADP-ribose) into mass spectrometry-friendly pR tags, thus facilitating the identification of ADP-ribosylation sites. PMID- 27406240 TI - Point mutation (R153H or R153C) in Escherichia coli isocitrate dehydrogenase: Biochemical characterization and functional implication. AB - Arginine 132 (R132) mutations to histidine or cysteine frequently occur to cytosolic NADP+ -isocitrate dehydrogenase (IDH1) in secondary glioblastoma multiforme (GBM) patients, in which GBM develops from a lower grade astroctyoma. Mutant enzymes lose the normal IDH activity, but acquire a neomorphic ability of producing 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate (alpha-KG). In the present study, the analogous mutations, Arg to His or Cys, were employed to homologous Arg153 of the NADP+ -IDH from Escherichia coli (EcIDH), generating two mutants: EcIDH R153 H and EcIDH R153C. The mutations dramatically reduced the catalytic efficiencies (kcat /Km ) of EcIDH R153H and EcIDH R153C for isocitrate oxidation, which dropped to only 0.6 and 1.5% of the wild-type enzyme, respectively. Neoenzymatic activities of catalyzing alpha-KG to 2-HG by EcIDH R153H and EcIDH R153C were confirmed by GC/TOF-MS analysis. The Km values of EcIDH R153H and EcIDH R153C displayed for alpha-KG were 3.3 +/- 0.12 and 2.2 +/- 0.13 mM, respectively, and the catalytic efficiencies (kcat /Km ) of the two mutants for alpha-KG were 300 and 450 M-1 s-1 , respectively. As human IDH1 Arg132 mutation is cancer-associated, the present study provides new information for the in-depth investigation of the metabolic influence of EcIDH Arg mutation in vivo. PMID- 27406241 TI - 3'-UTR engineering to improve soluble expression and fine-tuning of activity of cascade enzymes in Escherichia coli. AB - 3'-Untranslated region (3'UTR) engineering was investigated to improve solubility of heterologous proteins (e.g., Baeyer-Villiger monooxygenases (BVMOs)) in Escherichia coli. Insertion of gene fragments containing putative RNase E recognition sites into the 3'UTR of the BVMO genes led to the reduction of mRNA levels in E. coli. Importantly, the amounts of soluble BVMOs were remarkably enhanced resulting in a proportional increase of in vivo catalytic activities. Notably, this increase in biocatalytic activity correlated to the number of putative RNase E endonucleolytic cleavage sites in the 3'UTR. For instance, the biotransformation activity of the BVMO BmoF1 (from Pseudomonas fluorescens DSM50106) in E. coli was linear to the number of RNase E cleavage sites in the 3'UTR. In summary, 3'UTR engineering can be used to improve the soluble expression of heterologous enzymes, thereby fine-tuning the enzyme activity in microbial cells. PMID- 27406243 TI - Studies must show the value of regulatory schemes. PMID- 27406242 TI - TIME - Targeted interdisciplinary model for evaluation and treatment of neuropsychiatric symptoms: protocol for an effectiveness-implementation cluster randomized hybrid trial. AB - BACKGROUND: Nearly all persons with dementia will experience neuropsychiatric symptoms (NPS) during the course of their disease. Clinicians and researchers emphasize the need for an evidence-informed standardized approach to managing NPS that integrates pharmacological and nonpharmacological treatments for real-world implementation. The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) represents such an approach and is a multicomponent intervention based on the theoretical framework of cognitive behavioural therapy. METHODS/DESIGN: The trial is a 3-month cluster randomized trial conducted in 30 nursing homes including 168 participants with dementia and a high level of agitation. Each nursing home defined as a cluster will be randomized to receive either the TIME intervention (the intervention group) or a brief education-only intervention regarding dementia and NPS (the control group). TIME is a manual-based, multicomponent programme that includes a rigorous assessment, one or more case conferences and the treatment and evaluation of NPS. Patient-level measurements are taken at baseline (prior to randomization) and 8 and 12 weeks later. The primary outcome measure is the change in agitation, as defined by the Neuropsychiatric Inventory-Nursing Home Version, at 8 weeks from baseline. Secondary outcome measures include change in agitation at 12 weeks from baseline, and change from baseline at 8 and 12 weeks in other NPS, quality of life, and the use of psychotropic and analgesic medications. Mixed methods will be used to follow, measure and explore the implementation process and the effect of the intervention at the individual staff level and the organization level. Combining measurements of clinical effectiveness and implementation outcomes define this trial as an effectiveness-implementation hybrid trial. DISCUSSION: Measuring the implementation and effect of complex interventions aimed at reducing NPS in nursing homes is challenging. In this study protocol, we describe a multicomponent program, TIME, and discuss how an effectiveness-implementation cluster randomized hybrid trial can meet these challenges. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02655003 . Registered 6 January 2016. PMID- 27406244 TI - Dilemmas in the management of screen-detected lesions in patients at high risk for pancreatic cancer. AB - In 3-5 % of all cases of pancreatic ductal adenocarcinoma (PDAC), hereditary factors influence etiology. While surveillance of high-risk individuals may improve the prognosis, this study describes two very different outcomes in patients with screen-detected lesions. In 2000, a surveillance program of carriers of a CDKN2A/p16-Leiden-mutation consisting of annual MRI was initiated. Patients with a suspected pancreatic lesion undergo CT-scan and Endoscopic Ultrasound, and surgery is offered when a lesion is confirmed. In 2015, two patients with a screen-detected solid lesion were identified. In both patients, lesions were visible on MRI and CT scan, while the EUS was unremarkable. Surgical resection of the head of the pancreas resulted in nearly fatal complications in the first patient. This patient was shown to have a benign lesion. In contrast, timely identification of an early cancer in the second patient was accompanied by an uneventful postoperative course. These cases underline the risks inherent to a PDAC prevention program. All patients should be fully informed about the possible outcomes before joining a surveillance program. PMID- 27406245 TI - Gene expression profiling of brain cortex microvessels may support brain vasodilation in acute liver failure rat models. AB - Development of brain edema in acute liver failure can increase intracranial pressure, which is a severe complication of the disease. However, brain edema is neither entirely cytotoxic nor vasogenic and the specific action of the brain microvasculature is still unknown. We aimed to analyze gene expression of brain cortex microvessels in two rat models of acute liver failure. In order to identify global gene expression changes we performed a broad transcriptomic approach in isolated brain cortex microvessels from portacaval shunted rats after hepatic artery ligation (HAL), hepatectomy (HEP), or sham by array hybridization and confirmed changes in selected genes by RT-PCR. We found 157 and 270 up regulated genes and 143 and 149 down-regulated genes in HAL and HEP rats respectively. Western blot and immunohistochemical assays were performed in cortex and ELISA assays to quantify prostaglandin E metabolites were performed in blood of the sagittal superior sinus. We Identified clusters of differentially expressed genes involving inflammatory response, transporters-channels, and homeostasis. Up-regulated genes at the transcriptional level were associated with vasodilation (prostaglandin-E synthetase, prostaglandin-E receptor, adrenomedullin, bradykinin receptor, adenosine transporter), oxidative stress (hemoxygenase, superoxide dismutase), energy metabolism (lactate transporter) and inflammation (haptoglobin). The only down-regulated tight junction protein was occludin but slightly. Prostaglandins levels were increased in cerebral blood with progression of liver failure. In conclusion, in acute liver failure, up regulation of several genes at the level of microvessels might suggest an involvement of energy metabolism accompanied by cerebral vasodilation in the cerebral edema at early stages. PMID- 27406246 TI - Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder. AB - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD. PMID- 27406247 TI - CD146 Expression Influences Periapical Cyst Mesenchymal Stem Cell Properties. AB - Recent studies have identified a new human dental derived progenitor cell population with multi-lineage differentiation potential referred to as human periapical cyst mesenchymal stem cells (hPCy-MSCs). In the present study, we compared two subpopulations of hPCy-MSCs characterised by the low or high expression of CD146 to establish whether this expression can regulate their stem cell properties. Using flow cytometry, we evaluated the stem cell marker profile of hPCy-MSCs during passaging. Furthermore, CD146Low and CD146High cells were sorted by magnetic beads and subsequently both cell populations were evaluated for differences in their proliferation, self-renewal, stem cell surface markers, stemness genes expression and osteogenic differentiation potential.We found that hPCy-MSCs possessed a stable expression of several mesenchymal stem cell surface markers, whereas CD146 expression declined during passaging.In addition, sorted CD146Low cells proliferated significantly faster, displayed higher colony-forming unit-fibroblast capacity and showed higher expression of Klf4 when compared to the CD146High subset. Significantly, the osteogenic potential of hPCy-MSCs was greater in the CD146Low than in CD146High population. These results demonstrate that CD146 is spontaneously downregulated with passaging at both mRNA and protein levels and that the high expression of CD146 reduces the proliferative, self renewal and osteogenic differentiation potential of hPCy-MSCs. In conclusion, our study demonstrates that changes in the expression of CD146 can influence the stem cell properties of hPCy-MSCs. PMID- 27406248 TI - Rare novel variants in the ZIC3 gene cause X-linked heterotaxy. AB - Variants in the ZIC3 gene are rare, but have demonstrated their profound clinical significance in X-linked heterotaxy, affecting in particular male patients with abnormal arrangement of thoracic and visceral organs. Several reports have shown relevance of ZIC3 gene variants in both familial and sporadic cases and with a predominance of mutations detected in zinc-finger domains. No studies so far have assessed the functional consequences of ZIC3 variants in an in vivo model organism. A study population of 348 patients collected over more than 10 years with a large variety of congenital heart disease including heterotaxy was screened for variants in the ZIC3 gene. Functional effects of three variants were assessed both in vitro and in vivo in the zebrafish. We identified six novel pathogenic variants (1,7%), all in either male patients with heterotaxy (n=5) or a female patient with multiple male deaths due to heterotaxy in the family (n=1). All variants were located within the zinc-finger domains or leading to a truncation before these domains. Truncating variants showed abnormal trafficking of mutated ZIC3 proteins, whereas the missense variant showed normal trafficking. Overexpression of wild-type and mutated ZIC protein in zebrafish showed full non functionality of the two frame-shift variants and partial activity of the missense variant compared with wild-type, further underscoring the pathogenic character of these variants. Concluding, we greatly expanded the number of causative variants in ZIC3 and delineated the functional effects of three variants using in vitro and in vivo model systems. PMID- 27406249 TI - Novel microdeletions on chromosome 14q32.2 suggest a potential role for non coding RNAs in Kagami-Ogata syndrome. AB - In approximately 20% of individuals with Kagami-Ogata syndrome (KOS14, MIM 608149), characterized by a bell-shaped thorax with coat-hanger configuration of the ribs, joint contractures, abdominal wall defects and polyhydramnios during the pregnancy, the syndrome is caused by a maternal deletion of the imprinted gene cluster in chromosome 14q32.2. Most deletions reported so far included one or both of the differentially methylated regions (DMRs) - DLK1/MEG3 IG-DMR and MEG3-DMR. We present two unrelated families with two affected siblings each, presenting with classical KOS14 due to maternally inherited microdeletions. Interestingly, all four patients have lived through to adulthood, even though mortality rates for patients with KOS14 due to a microdeletion are relatively high. In the first family, none of the DMRs is included in the deletion and the methylation status is identical to that of controls. Deletions that do not encompass the DMRs in this region are thus sufficient to elicit the full KOS14 phenotype. In the second family, a partially overlapping deletion including both DMRs and MEG3 was detected. In summary, we show that patients with KOS14 can live into adulthood, that causal deletions do not have to include the DMRs and that consequently a normal methylation pattern does not exclude KOS14. PMID- 27406250 TI - Genotype and brain pathology phenotype in children with tuberous sclerosis complex. AB - Structural brain malformations associated with Tuberous Sclerosis Complex (TSC) are related to the severity of the clinical symptoms and can be visualized by magnetic resonance imaging (MRI). Tuberous Sclerosis Complex is caused by inactivating TSC1 or TSC2 mutations. We investigated associations between TSC brain pathology and different inactivating TSC1 and TSC2 variants, and examined the potential prognostic value of subdivision of TSC2 variants based on their predicted effects on TSC2 expression. We performed genotype-phenotype associations of TSC-related brain pathology on a cohort of 64 children aged 1.4 17.9 years. Brain abnormalities were assessed using MRI. Individuals were grouped into those with an inactivating TSC1 variant and those with an inactivating TSC2 variant. The TSC2 group was subdivided into changes predicted to result in TSC2 protein expression (TSC2p) and changes predicted to prevent expression (TSC2x). The TSC2 group was associated with more and larger tubers, more radial migration lines, and more subependymal nodules than the TSC1 group. Subependymal nodules were also more likely to be calcified. Subdivision of the TSC2 group did not reveal additional, substantial differences, except for a larger number of tubers in the temporal lobe and a larger fraction of cystic tubers in the TSC2x subgroup. The severity of TSC-related brain pathology was related to the presence of an inactivating TSC2 variant. Although larger studies might find specific TSC2 variants that have prognostic value, in our cohort, subdivision of the TSC2 group did not lead to better prediction. PMID- 27406252 TI - Erratum to: Statokinesigram normalization method. PMID- 27406251 TI - [New S3 guideline for esophageal cancer : Important surgical aspects]. AB - The current German S3 guideline represents the recommendations for the diagnosis and therapy of squamous cell carcinomas and adenocarcinomas of the esophagus based on evidence from the literature and interdisciplinary expert consensus. Esophagogastroscopy with biopsy, endosonography, and spiral CT scan of the neck, thorax, and abdomen are decisive in staging and the choice of therapy. For a curative approach, surgery, especially transthoracic esophagectomy and gastric pull-up, is the most important therapeutic option, except in the case of mucosal carcinomas or cervical squamous cell carcinomas. The significance of total minimally invasive esophageal resection or a hybrid technique is still uncertain. In category cT3 or resectable cT4 tumors, neoadjuvant radiochemotherapy should be performed in squamous cell carcinomas or adenocarcinomas. Alternatively, perioperative chemotherapy can be carried out in adenocarcinoma. Palliative resections should be avoided and replaced by interventional procedures for palliation. PMID- 27406253 TI - Formality of the Chinese collective leadership. AB - We investigated the linguistic patterns in the discourse of four generations of the collective leadership of the Communist Party of China (CPC) from 1921 to 2012. The texts of Mao Zedong, Deng Xiaoping, Jiang Zemin, and Hu Jintao were analyzed using computational linguistic techniques (a Chinese formality score) to explore the persuasive linguistic features of the leaders in the contexts of power phase, the nation's education level, power duration, and age. The study was guided by the elaboration likelihood model of persuasion, which includes a central route (represented by formal discourse) versus a peripheral route (represented by informal discourse) to persuasion. The results revealed that these leaders adopted the formal, central route more when they were in power than before they came into power. The nation's education level was a significant factor in the leaders' adoption of the persuasion strategy. The leaders' formality also decreased with their increasing age and in-power times. However, the predictability of these factors for formality had subtle differences among the different types of leaders. These results enhance our understanding of the Chinese collective leadership and the role of formality in politically persuasive messages. PMID- 27406254 TI - Is satisfaction with surgeon a determining factor in patient reported outcomes in breast reconstruction? AB - BACKGROUND: Patient reported outcomes are increasingly being taken into account in planning health service provision. Few studies have examined how the process of care influences patients' perception of outcome. The aim of the current study was to quantify patient satisfaction with breast reconstruction and to examine the demographic, disease and process-of-care variables that contributed to satisfaction with breasts and overall outcome. METHODS: A cross-sectional study was designed and the BREAST-Q outcomes assessment instrument was used to evaluate patient-reported psychosocial, physical and sexual well-being, as well as satisfaction with breasts, overall outcome and process of care. To identify factors predictive of satisfaction with breasts and overall outcome, the relation between covariates and each of these scales was assessed using linear regression models. RESULTS: Sixty one patients, with a mean age of 50 years, completed the survey. Mean satisfaction with breasts was 59.6% and satisfaction with overall outcome was 73.2%. Satisfaction across health-related quality of life scales ranged from 44.6% for sexual well-being to 74.6% for physical well-being. The mean rating for psychosocial well-being was 67.9%. Satisfaction ratings for surgeon, medical staff and office staff were all over 90%. Satisfaction with plastic surgeon was predictive of satisfaction with outcome and satisfaction with breasts (P = 0.001 and 0.021 respectively). DISCUSSION: The surgeon-patient relationship significantly influences patient reported outcomes in breast reconstruction. Further service development must recognize the need for additional time and personnel to deliver high standard, patient-centered care. PMID- 27406255 TI - Quality of life following total mastectomy with and without reconstruction versus breast-conserving surgery for breast cancer: A case-controlled cohort study. AB - BACKGROUND: Patient-reported outcomes and quality of life following mastectomy are not well understood. This study evaluates the quality of life following surgery for breast cancer and compares outcomes following breast-conserving surgery versus total mastectomy with or without reconstruction. METHODS: A case controlled cross-sectional study was conducted using the validated BREAST-QTM questionnaire and a study-specific questionnaire to determine patient's views about surgical outcomes. Questionnaires were completed by patients following breast-conserving surgery and total mastectomy with or without reconstruction and by controls without breast cancer. A one-way ANOVA was used to compare mean BREAST-QTM scores between groups and post hoc analysis using Tukey's and Kruskal Wallis tests. RESULTS: BREAST-QTM questionnaires were completed by 400 women (123 controls, 97 breast conservations, 93 mastectomies without reconstruction, 87 mastectomies with reconstruction). Women who had undergone mastectomy and reconstruction had higher scores in satisfaction with breast and sexual well being domains compared with women who had breast-conserving surgery, and women who had total mastectomy without reconstruction had the lowest scores in these two domains. There was no difference in psychosocial well-being between the groups. Women who had undergone breast-conserving surgery scored the lowest in the physical well-being chest domain and the majority reported breast asymmetry. CONCLUSION: Our study suggests that women who undergo total mastectomy and breast reconstruction for cancer achieve a quality-of-life outcome that is at least as good as that following breast-conserving surgery. Furthermore, breast conservation has been found to be associated with lower physical well-being (i.e., more pain and discomfort) in the chest area and poorer sexual well-being outcomes. PMID- 27406256 TI - Long-term outcomes with the McGhan Style 153 dual-lumen breast implant: Implications for future implant design. AB - BACKGROUND: A variety of saline and silicone implants have been introduced over the years to optimize the shape, aesthetic result and safety profile for use in breast surgery. The McGhan Style 153 dual-lumen silicone implant represented an early generation of anatomically shaped implants later removed from the market due to a high rate of rupture. This study reports long term outcomes and complications, including a revised rupture rate, and discusses potential mechanisms of implant failure and their implications for future implant design. METHODS: A retrospective review was performed on 79 patients (134 implants). Demographics, operative details, outcomes, and complications were recorded. Rupture rate and location of rupture were included. RESULTS: The revised implant rupture rate was 36.6% of implants. At least one rupture occurred in 49.4% of patients. Clinical exam was the most common method of detection (55.1% of ruptures). The most common location of rupture was the superior pole (30.6%), followed by a posterior location (24.5%). The capsular contracture rate (Baker grade III/IV) was 51.5%. The total implant removal rate (for rupture, contracture, size change, or asymmetry) was 77.6%. The average time to implant removal was 91.8 months, or 7.5 years (+/-47.3 months). Average follow up was 120.7 months or 10 years (+/-49.9 months). DISCUSSION: The experiences with this anatomic gel implant highlight the importance of shell stability over time, suitable gel cohesiveness to support the asymmetric anatomic shape, avoidance of fold flaws due to wrinkling, and the prevention of distinct stress points on the shell that can result from dual lumen or multi-compartment designs. LEVEL OF EVIDENCE: Level III, retrospective cohort, therapeutic study. PMID- 27406257 TI - Energy intake, energy required and mortality in an older population. AB - OBJECTIVES: The present study evaluated the association between energy intake, energy required and mortality in older adults. DESIGN: A cohort study with a mean of 10.67 (sd 4.74) years of follow-up. Participants completed a 24 h dietary recall. Energy required per day was computed by BMR. Deaths through 2006 were identified from the National Death Index. A Cox regression was used to estimate the hazard ratios (HR) of quantiles of energy intake and energy required on all cause and CVD mortality, adjusting for demographics, socio-economic status and co morbidity. SETTING: The National Health and Nutrition Examination Survey (NHANES) III, 1988-1994. SUBJECTS: A total of 4846 participants aged 60 years or above were analysed. RESULTS: Within the follow-up period, there were a total of 2954 deaths (61.0 %), 51.9 % were caused by CVD. Relative to those in quartile 1 of energy intake, only quartile 4 was associated with all-cause mortality and CVD mortality with HR of 0.86 (95 % CI 0.77, 0.96, P=0.006) and 0.76 (95 % CI 0.65, 0.89, P=0.001), respectively. On the other hand, relative to those in quartile 1 of energy required, all quartiles of participants had a lower risk of all-cause mortality and CVD mortality. The interaction effects between energy intake and energy required with all-cause and CVD mortality were insignificant (P=0.70 and 0.61, respectively). CONCLUSIONS: Independent of energy required, higher energy intake was associated with lower HR of both all-cause and CVD mortality in older adults. PMID- 27406258 TI - Revealing instability and irreversibility in nonaqueous sodium-O2 battery chemistry. AB - Charging kinetics and reversibility of Na-O2 batteries can be influenced greatly by the particle size of NaO2 formed upon discharge, and exposure time (reactivity) of NaO2 to the electrolyte. Micrometer-sized NaO2 cubes formed at high discharge rates were charged at smaller overpotentials compared to nanometer sized counterparts formed at low rates. PMID- 27406260 TI - pH-Induced aggregated melanin nanoparticles for photoacoustic signal amplification. AB - We present a new melanin-like nanoparticle (MelNP) and its performance evaluation results. This particle is proposed as an exogenous contrast agent for photoacoustic (PA) imaging. Conventional PA contrast agents are based on non biological materials. In contrast, the MelNPs are organic nanoparticles inspired by natural melanin. Melanin is an endogenous chromophore that has the ability to produce a PA signal in vivo. The developed MelNPs are capable of aggregating with one another under mildly acidic conditions after introducing hydrolysis susceptible citraconic amide on the surface of bare MelNPs. We ascertained that the physical aggregation of the MelNPs resulted in an increased PA signal strength in the near-infrared window of biological tissue (i.e., 700 nm) without absorption tuning. This phenomenon is likely because of the overlapping thermal fields of the developed MelNPs. The PA signal produced from the developed MelNPs, after exposure to mildly acidic conditions (i.e., pH 6), is 8.1 times stronger than under neutral conditions. This unique characteristic found in this study can be utilized in a practical strategy for highly sensitive in vivo cancer target imaging in response to its acidic microenvironment. This approach to amplify the PA response of MelNPs in clusters could accelerate the use of MelNPs as an alternative to non-biological nanoprobes, so that MelNPs may be applicable in PA imaging and functional PA imaging such as stimuli sensitive, multimodal, and theranostic imaging. PMID- 27406259 TI - Early injury of the neonatal lung contributes to premature lung aging: a hypothesis. AB - Chronic lung disease of the newborn, also known as bronchopulmonary dysplasia (BPD), is the most common chronic lung disease in early infancy and results in an increased risk for long-lasting pulmonary impairment in the adult. BPD develops upon injury of the immature lung by oxygen toxicity, mechanical ventilation, and infections which trigger sustained inflammatory immune responses and extensive remodeling of the extracellular matrix together with dysregulated growth factor signaling. Histopathologically, BPD is characterized by impaired alveolarization, disrupted vascular development, and saccular wall fibrosis. Here, we explore the hypothesis that development of BPD involves disturbance of conserved pathways of molecular aging that may contribute to premature aging of the lung and an increased susceptibility to chronic lung diseases in adulthood. PMID- 27406261 TI - Vertical variation of bacterial community in Nam Co, a large stratified lake in central Tibetan Plateau. AB - We assessed the vertical variation of bacterial abundance, diversity and community composition in deep, high-altitude (4730 m above sea level) Lake Nam Co. The bacterial abundance reduced with increasing depth, while bacterial diversity increased in the deeper bottom water. Pyrosequencing revealed that the bacterial community in the lake showed a pronounced vertical shift: the Bacteroidetes and Proteobacteria had relatively higher abundance in the epilimnion and metalimnion; the Firmicutes group dominated in the metalimnion; the Actinobacteria and Cyanobacteria mainly occupied the metalimnion and hypolimnion. Water temperature, conductivity, photosynthetically active radiation, and chlorophyll a were significantly correlated with the bacterial communities. These results indicated that the bacterial communities appeared to have an apparent vertical structure under lake stratification. PMID- 27406262 TI - I-131 for Remnant Ablation in Differentiated Thyroid Cancer After Thyroidectomy: A Meta-Analysis of Randomized Controlled Evidence. AB - BACKGROUND The aim of this study was to compare the success rate of various levels of I-131 activity for use in remnant ablation in low-risk differentiated thyroid cancer. MATERIAL AND METHODS We identified eligible studies in 5 electronic databases up to December 2014 and the reference lists of original studies and review articles were hand searched for additional articles on this topic. Summary relative risks with their 95% confidence intervals were calculated with a random-effects model. Heterogeneity was assessed using I2 statistics. RESULTS Fourteen randomized clinical trials met the eligibility criteria. The data suggest that the pooled successful ablation rate is 5% lower (95% CI, 1-9% lower) when using 30 mCi compared with 100 mCi (test for heterogeneity, p=0.468, I2=0.0%). In stratified analysis, ablation success rates using 30 mCi are similar to 100 mCi in Asia (SRRs=0.91; 95%CI=0.72-1.14). However, the results favor 100 mCi in Europe (SRRs=0.95; 95%CI=0.91-0.99). Ablation success rates using 30 mCi are similar to 100 mCi in patients who underwent TT/NTT (total thyroidectomy/near total thyroidectomy) (SRRs=0.96; 95%CI=0.92-1.00) and TT/STT (SRRs=0.98; 95%CI=0.73-1.31). However, the result favor 100 mCi in patients who underwent ST/HT (subtotal thyroidectomy/ hemithyroidectomy) (SRRs=0.80; 95%CI=0.65-0.99). There was no publication bias in the present meta-analysis. CONCLUSIONS High radioiodine activity is better than low activity in terms of successful ablation rate in low-risk differentiated thyroid cancer, but the advantage of high activity seems to only exist in patients who underwent hemithyroidectomy/subtotal thyroidectomy, but not lymph node involvement, preparation before ablation, and definition of successful ablation. PMID- 27406264 TI - Coping strategies in anxious surgical patients. AB - BACKGROUND: Anaesthesia and surgery provoke preoperative anxiety and stress. Patients try to regain control of their emotions by using coping efforts. Coping may be more effective if supported by specific strategies or external utilities. This study is the first to analyse coping strategies in a large population of patients with high preoperative anxiety. METHODS: We assessed preoperative anxiety and coping preferences in a consecutive sample of 3087 surgical patients using validated scales (Amsterdam Preoperative Anxiety and Information Scale/Visual Analogue Scale). In the subsample of patients with high preoperative anxiety, patients' dispositional coping style was determined and patients' coping efforts were studied by having patients rate their agreement with 9 different coping efforts on a four point Likert scale. Statistical analysis included correlational analysis between dispositional coping styles, coping efforts and other variables such as sociodemographic data. Statistical significance was considered for p < 0.05. RESULTS: The final analysis included 1205 patients with high preoperative anxiety. According to the initial self-assessment, about two thirds of the patients believed that information would help them to cope with their anxiety ("monitors"); the remainder declined further education/information and reported self-distraction to be most helpful to cope with anxiety ("blunters"). There was no significant difference between these two groups in anxiety scores. Educational conversation was the coping effort rated highest in monitors whereas calming conversation was the coping effort rated highest in blunters. Coping follows no demographic rules but is influenced by the level of education. Anxiolytic Medication showed no reliable correlation to monitoring and blunting disposition. Both groups showed an exactly identical agreement with this coping effort. Demand for medical anxiolysis, blunting or the desire for more conversation may indicate increased anxiety. The use of the internet was independent of the anxiety level and the demand of information. CONCLUSION: Conversation with medical staff proved to be the most popular coping strategy. Acknowledgment of the division between information-seeking and blunting-like personalities is central to supporting the patient's individual coping efforts. Internet access may be the easiest way to support coping today. PMID- 27406263 TI - Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice. AB - BACKGROUND: Apolipoprotein E (ApoE) is a major lipid carrier that supports lipid transport and injury repair in the brain. The APOE epsilon4 allele is associated with depression, mild cognitive impairment (MCI) and dementia; however, the precise molecular mechanism through which ApoE4 influences the risk of disease development remains unknown. To address this gap in knowledge, we investigated the potential effects of chronic unpredictable mild stress (CUMS) on ApoE3 and ApoE4 target replacement (ApoE3-TR and ApoE4-TR) mice. RESULTS: All ApoE-TR mice exposed to CUMS at 3 months old recovered from a depression-like state by the age of 12 months. Of note, ApoE4-TR mice, unlike age-matched ApoE3-TR mice, displayed impaired spatial cognitive abilities, loss of GABAergic neurons, decreased expression of Reelin, PSD95, SYN and Fyn, and reduced phosphorylation of NMDAR2B and CREB. CONCLUSION: These results suggest that early-life stress may mediate cognitive impairment in middle-age ApoE4-TR mice through sustained reduction of GABAergic neurons and Reelin expression, which might further diminish the activation of the Fyn/NMDAR2B signaling pathway. PMID- 27406265 TI - Nile Red and Nile Blue: Applications and Syntheses of Structural Analogues. AB - Nile red and Nile blue are highly fluorescent and photostable organic dyes from the benzo[a]phenoxazine family. They have been used as histological stains for imaging lysosomes and lipids in vitro. The dyes' high quantum yields and solvent dependent optical properties make them ideal scaffolds for the development of pH probes and local polarity indicators. Reviews of the literature in this area are scarce with only one review ever published in 2006. It has been 10 years since and the field has evolved. This review aims to expand upon topics covered by the previous reviewers and to report on recent advances in the literature. As authors, we hope to convey a sense of scope and to spark renewed interest in this useful niche of dye chemistry. PMID- 27406266 TI - TolC plays a crucial role in immune protection conferred by Edwardsiella tarda whole-cell vaccines. AB - Although vaccines developed from live organisms have better efficacy than those developed from dead organisms, the mechanisms underlying this differential efficacy remain unexplored. In this study, we combined sub-immunoproteomics with immune challenge to investigate the action of the outer membrane proteome in the immune protection conferred by four Edwardsiella tarda whole-cell vaccines prepared via different treatments and to identify protective immunogens that play a key role in this immune protection. Thirteen spots representing five outer membrane proteins and one cytoplasmic protein were identified, and it was found that their abundance was altered in relation with the immune protective abilities of the four vaccines. Among these proteins, TolC and OmpA were found to be the key immunogens conferring the first and second highest degrees of protection, respectively. TolC was detected in the two effective vaccines (live and inactivated-30-F). The total antiserum and anti-OmpA titers were higher for the two effective vaccines than for the two ineffective vaccines (inactivated-80-F and inactivated-100). Further evidence demonstrated that the live and inactivated 30-F vaccines demonstrated stronger abilities to induce CD8+ and CD4+ T cell differentiation than the other two evaluated vaccines. Our results indicate that the outer membrane proteome changes dramatically following different treatments, which contributes to the effectiveness of whole-cell vaccines. PMID- 27406267 TI - The roles of amensalistic and commensalistic interactions in large ecological network stability. AB - Ecological communities comprise diverse species and their interactions. Notably, ecological and evolutionary studies have revealed that reciprocal interactions such as predator-prey, competition, and mutualism, are key drivers of community dynamics. However, there is an argument that many species interactions are asymmetric, where one species unilaterally affects another species (amensalism or commensalism). This raises the unanswered question of what is the role of unilateral interactions in community dynamics. Here I use a theoretical approach to demonstrate that unilateral interactions greatly enhance community stability. The results suggested that amensalism and commensalism were more stabilizing than symmetrical interactions, such as competition and mutualism, but they were less stabilizing than an asymmetric antagonistic interaction. A mix of unilateral interactions increased stability. Furthermore, in communities with all interaction types, unilateral interactions tended to increase stability. This study suggests that unilateral interactions play a major role in maintaining communities, underlining the need to further investigate their roles in ecosystem dynamics. PMID- 27406268 TI - Computational insights into CdSe quantum dots' interactions with acetate ligands. AB - Using density functional theory (DFT) and time-dependent DFT (TDDFT), we investigate the effects of carboxylate groups on the electronic and optical properties of CdSe quantum dots (QDs). We specifically focus on the mechanisms of the binding of the acetate anion to the QD surface with and without excess of Cd(2+) cations. Our calculations show that the most stable ligated conformations are those where an acetate is attached to extra Cd(2+) ion forming a [Cd(2+)(CH3COO(-))] at the QD's surface, while also accompanied by an acetate attached nearby at the surface balancing the overall neutral charge of the system. In contrast, formation of a neutral metal-acetate complex [Cd(2+)(CH3COO( ))2] at the QD surface is found to be the least energetically preferable. A strength of the QD-ligand interaction depends on the solvent, the facet of the QD to which the ligands are attached, and the binding mode - with the bridging mode found to be the most stable conformation for both acetate and cadmium acetate ligands. The cadmium acetate ligands introduce electron trap states at the edge of the conduction band - unoccupied orbitals predominately localized on Cd(2+) ion - that are extremely sensitive to the ligand position and the solvent polarity. Polar solvents like acetonitrile delocalize the electronic density over the entire system and, thus, eliminate trap states. As a result, mixed passivation of the CdSe QDs by pairs of cadmium acetate and acetate ligands provides optimal optical properties with minimal contributions of the ligand related trap states and optically bright lowest energy transitions. PMID- 27406269 TI - Iron: The Essential Poison. PMID- 27406270 TI - Control of the pro-oxidant-dependent calcium release from intact liver mitochondria. AB - The reduction of molecular oxygen to water provides most of the energy that enables higher organisms to exist. Oxygen reduction is a mixed blessing because incompletely reduced oxygen species are more reactive than molecular oxygen in the ground state and can, when out of control, damage biological molecules. However, incompletely reduced oxygen species may also serve useful functions, as exemplified by their control of mitochondrial Ca(2+) homeostasis, the understanding of which has improved greatly during the last few years. Hydrogen peroxide can stimulate a specific Ca(2+) release pathway from intact mitochondria by oxidizing mitochondrial pyridine nucleotides through the activities of glutathione peroxidase, glutathione reductase, and the energy-linked transhydrogenase. Other pro-oxidants such as menadione, alloxan, or divicine also stimulate the specific Ca(2+) release, because they furnish NAD(+). The specific Ca(2+) release requires for its activation the hydrolysis of intramitochondrial NAD(+) to ADPribose and nicotinamide, and is prevented by inhibitors of NAD(+) hydrolysis and protein monoADPribosylation. Recent experiments reveal that NAD(+) hydrolysis and therefore Ca(2+) release is regulated by vicinal thiols in mitochondria. When reduced or alkylated, the thiols prevent hydrolysis, but when they are cross-linked hydrolysis takes place. Cyclosporine A, which also prevents NAD(+) hydrolysis, acts distal of these vicinal thiols. Since mitochondrial Ca(2+) handling is physiologically relevant, its control by pro-oxidants must be added to the growing list of their useful functions. PMID- 27406271 TI - Synthesis and role of glutathione in protection against oxidative stress in yeast. AB - Glutathione (GSH) is an abundant and ubiquitous low-molecular-mass thiol with proposed roles in many cellular processes including amino acid transport, synthesis of proteins and nucleic acids, modulation of enzyme activity and metabolism of xenobiotics, carcinogens and reactive oxygen species. This review describes recent findings in the lower eukaryote Saccharomyces cerevisiae that are leading to a better understanding of the role of this peptide in eukaryotic cell metabolism. In particular, two gene products involved in maintaining the levels of reduced GSH have been studied; namely, GSH1 encoding gamma glutamylcysteine synthetase, the first step in the biosynthesis of GSH, and glutathione reductase, which recycles glutathione to its reduced form. These studies indicate that GSH is an essential metabolite in yeast, and that it is required for protection against oxidative stress produced by mitochondrial metabolism and exogenous reactive oxygen species. These findings are discussed in the light of analogous observations made in higher eukaryotes. PMID- 27406272 TI - Uric acid: friend or foe? PMID- 27406273 TI - Starvation-induced autophagocytosis enhances the susceptibility of insulinoma cells to oxidative stress. AB - We have previously shown insulinoma (HIT-T15 and RINm5F) cells in culture to be very sensitive, in comparison with a reference cell line (J-774), to the oxidative stress that is created when alloxan reacts extracellularly with reducing agents, forming superoxide and hydrogen peroxide. The toxic effects are prevented by catalase added to the medium, suggesting that alloxan does not need to be taken up in order to affect cells. Rather, alloxan seems to exert its action through extracellular formation of hydrogen peroxide that influences the stability of the cells' lysosomes following diffusion into them. To further analyse the mechanisms in operation, we studied the influence of induced autophagocytosis on the sensitivity to ensuing oxidative stress. Starvation for 60-120 min in PBS at 37 degrees C markedly enhanced autophagocytosis and, in parallel, increased the cytotoxic effect and lysosomal vulnerability of ensuing exposure to hydrogen peroxide, while not significantly changing the antioxidative status or the energy balance. Autophagocytosis increased the size of the intralysosomal pool of reactive, low-molecular-weight, iron, probably by degradation of metallo-proteins, as shown by autometallography and HPLC demonstration of desferrioxamine-reactive intracellular iron. Moreover, exposure to the iron-chelator desferrioxamine before treatment with hydrogen peroxide prevented lysosomal destabilization and cellular death of both starved and control cells, further proving the importance of intralysosomal iron for the response to oxidative stress. We hypothesize that beta-cells which, like insulinoma cells, have a weak antioxidative defence system under conditions of enhanced general autophagocytosis, or crinophagy, might become vulnerable to even low, or moderate, oxidative stress. PMID- 27406274 TI - Effects of hydrogen peroxide, nitric oxide and antioxidants on NF-kappaB. AB - The NF-kappaB complex consists of a family of transcription factors which bind to specific sequences present in the regulatory regions of mammalian genes and in the human immunodeficiency virus (HIV) long terminal repeat. It has been suggested that free radicals may play a role in NF-kappaB activation and in the activation of HIV expression. The effects of H2O2 and nitric oxide (NO(*)) on NF kappaB deoxyribonucleic acid (DNA) binding were examined using the electrophoretic mobility shift assay. When nuclear protein extracts containing NF kappaB are treated with H2O2 in vitro, DNA binding to the kappaB consensus element is inhibited, although the NF-kappaB heterodimer remains intact. This inhibitory effect is concentration- and temperature-dependent and can be reversed by the reducing agent dithiothreitol (DTT). Co-incubation with reduced glutathione protects nuclear extracts from H2O2, while other antioxidants such as vitamin C and the chelators deferoxamine and diethyldithiocarbamate provide no such protection. The thiol blocker iodoacetate also inhibits DNA binding similar to H2O2, suggesting that protein thiols are involved. The nitric oxide generating compound diethylamine NONOate inhibits the binding of NF-kappaB to DNA in vitro. This DNA binding inhibition may also be due to an interaction with protein thiols, since it is also reversible with DTT. Thus, although H2O2 and NO(*) activate NF-kappaB in vivo, they inhibit DNA binding in a cell-free system. This paradox suggests the involvement of other factors in the activation of NF-kappaB mediated transcription. A better understanding of this process will aid in an understanding of the pathogenesis of acquired immune deficiency syndrome (AIDS). PMID- 27406275 TI - Vitamin C in premature and full-term human neonates. AB - Plasma concentrations of vitamin C (ascorbic acid, AA) are known to be higher in full-term human neonates than their mothers. Immaturity of placental AA transport could result in low plasma AA concentrations in pre-term infants. We found that plasma AA concentrations in umbilical cord blood of 25 full-term neonates (38-42 weeks gestation) and 33 pre-term neonates (24-36 weeks gestation) were always significantly higher than in the corresponding maternal blood (P < 0.0001). However, plasma AA levels were significantly higher in pre-term than in full-term infants (146 +/- 93 vs 102 +/- 27 MUM, respectively; P = 0.03). Furthermore, a rapid and sharp decrease in plasma AA concentrations from 229 +/- 166 MUM to 45 +/- 18 MUM (P < 0.0001) over the first 3 days of life was observed in eight very low birth weight infants (460-1090 g, 24-28 weeks gestation). These findings raise important questions about the in utero functions of AA in the developing fetus and the adequacy of postnatal vitamin C supplementation of the premature infant. PMID- 27406276 TI - Accelerated disulfide reduction with polyunsaturated fatty acids: a mechanism of ionic channel modulation? AB - Polyunsaturated fatty acids (PUFAs) have been shown to modulate the activity of ionic channels by an unknown mechanism. Some channels are activated (i.e. certain delayed-rectifier, potassium channels) and others are inhibited (i.e. certain calcium, sodium and other potassium channels). We have previously demonstrated that PUFAs can act as electron carriers. It is known that ionic channels can be redox modulated. The ability of fatty acids to serve as electron shuttling agents is proportional to their unsaturation. These PUFAs cause reduction of disulfides through a superoxide radical-independent mechanism, probably related to enhanced electron delocalization. The present study shows that there is a strong correlation between the ability of a PUFA to transfer an electron to a disulfide and its reported ability to modulate ionic channels. This suggests that electron transfer could be the mechanism of PUFAs action on particular ionic channels. PMID- 27406277 TI - Effect of acute skin thermal injury on subcutaneous glutathione, ascorbic acid and hydroxyl radical concentrations in anesthetized rats. AB - The effect of acute thermal injury on subcutaneous oxidative stress, in anesthetized rats, was evaluated. A microdialysis probe was implanted in the subcutaneous tissue for continuous sampling of interstitial fluids, and the microdialysates were injected onto either an on-line or an off-line high performance liquid chromatography system. Hydroxyl radicals, glutathione, and ascorbic acid concentrations in the microdialysates were analyzed. Acute thermal injury was induced by skin contact of a hot (90 degrees C) iron bar for 30 or 15 s. Subcutaneous hydroxyl radical production, represented as the increased formation of 2,3 and 2,5 dihydroxybenzoic acid (DHBA), did not increase significantly after thermal contact. Interestingly, both ascorbic acid and glutathione, two major physiological antioxidants, were significantly elevated in the subcutaneous interstitial fluids immediately after thermal contacts. The elevated subcutaneous glutathione levels rapidly decreased and returned to basal values 60 min after thermal contact. Ascorbic acid concentrations did not fully return to basal values even 3 h after thermal contact. The increase in ascorbic acid and glutathione may be responsible for scavenging of hydroxyl radicals that may form following thermal injury. PMID- 27406278 TI - Post-transcriptional control of increased hepatic catalase gene expression in response to oxidative stress. AB - Catalase is an important member of the antioxidant network that protects the cell against reactive oxygen species (ROS). We studied catalase gene expression in the liver of rats exposed to oxidative stress induced by the ROS-generating drug nitrofurantoin (NF). Catalase enzymatic activity and content are enhanced by NF treatment. The corresponding increase in the steady state level of the messenger ribonucleic acid (mRNA) occurs without significant changes in transcription and seems therefore controlled post-transcriptionally. Indeed, RNA band-shift assays demonstrated a reduced binding of redox-sensitive cytoplasmic protein(s) to the 3' region of catalase mRNA in NF-treated rats, thus suggesting that the redox state of protein that binds to an antioxidant enzyme mRNA may play a role in the hepatic response to oxidative stress. PMID- 27406279 TI - Structure and redox properties of one-electron oxidized radicals from adenine and derivatives. AB - The reaction of sulphate radical anion (SO(4*-)) with adenine and its derivatives results in the formation of a neutral radical at pH 7, whose spin distribution and hence the oxidizing properties are strongly dependent on the position and nature of the substituents. This reaction proceeds by one electron transfer, followed by rapid deprotonation of the incipient radical cation, the sequence of these reactions being equivalent to hydrogen abstraction. In adenine radical cation, deprotonation was found to occur either from N(6)-H or N(9)-H, leading to the formation of a strong and a less oxidizing radical, respectively. Among adenine derivatives, adenosine was shown to give rise to the most oxidizing neutral radical, whilst the least oxidizing radical was formed from N(6),N(6) dimethyladenine. PMID- 27406280 TI - Cytoplasmic pH modulates the activity of the plasma membrane electron transport system in Ehrlich ascites tumour cells. AB - We report evidence for a modulation of Ehrlich cell plasma membrane redox activity by cytoplasmic pH. When Ehrlich cells were submitted to treatments leading to a slight decrease of cytoplasmic pH, there was a significant inhibition of plasma membrane ferricyanide reductase activity. However, those treatments which produced a slight alkalinization of the cytoplasm enhanced the activity of the plasma membrane redox system. Since it has been shown previously that plasma membrane redox activity controls cytoplasmic pH, it seems that plasma membrane redox activity and cytoplasmic pH mutually modulate each other. PMID- 27406281 TI - Correspondence. PMID- 27406283 TI - [Not Available]. PMID- 27406284 TI - [Not Available]. PMID- 27406282 TI - Suicidality in Bipolar Disorder: The Role of Emotion-Triggered Impulsivity. AB - A growing body of research suggests that impulsive responses to emotion more robustly predict suicidality than do other forms of impulsivity. This issue has not yet been examined within bipolar disorder, however. Participants diagnosed with bipolar I disorder (n = 133) and control participants (n = 110) diagnosed with no mood or psychotic disorder completed self-report measures of emotion triggered impulsivity (Negative and Positive Urgency Scales) and interviews concerning lifetime suicidality. Analyses examined the effects of emotion triggered impulsivity alone and in combination with gender, age of onset, depression severity, comorbid anxiety, comorbid substance use, and medication. A history of suicide ideation and attempts, as well as self-harm, were significantly more common in the bipolar disorder group compared with the control group. Impulsive responses to positive emotions related to suicide ideation, attempts, and self-harm within the bipolar group. Findings extend research on the importance of emotion-triggered impulsivity to a broad range of key outcomes within bipolar disorder. The discussion focuses on limitations and potential clinical implications. PMID- 27406285 TI - [Granulomatose med polyangiitis kan debutere som isoleret gingivitis]. PMID- 27406286 TI - [Liquorice consumption may induce torsades de pointes ventricular tachycardia]. AB - This case report describes an often forgotten cause of hypokalaemia resulting in electrocardiograpic changes in a 75-year-old man known with hypertension, atrial fibrillation and ischaemic heart disease. A detailed anamnesis, a prompt replacement of potassium and cessation of liquorice consumption resulted in a favourable outcome. PMID- 27406287 TI - [The internal carotid artery as a pulsating protrusion into the pharyngeal wall]. AB - This case report describes an aberrant course of the internal carotid artery (ICA) in a patient presenting with symptoms of globus sensation, mild chronic cough and occasional aspiration. Clinically, a pulsating oro-hypopharyngeal tumour could only be visualized by fiberlaryngoscopy. A CT-scan showed a tortuous ICA protruding into the lateral and posterior pharyngeal wall. This condition may need treatment in itself, and it can lead to co-morbidity and serious surgical complications in undiagnosed patients. Referral to an oto-rhino-laryngologist is highly recommended for diagnostics. PMID- 27406288 TI - [Uterine necrosis upon acute caesarean section in a homozygous factor VLeiden patient]. AB - Peripartum hysterectomy is a rare but life-saving procedure. Haemorrhage, atony, placenta accreta/praevia or uterus rupture are the most common reasons for hysterectomy. This case report presents a 35-year-old woman, gravida 2, para 1, with total necrosis of the uterus and ovaries bilaterally after an acute caesarean section. Pathological examination showed thrombosis and haemorrhagic infarction. Besides pre-eclampsia the patient had no co-morbidity. Later analysis found homozygosity for factor VLeiden mutation. Hysterectomy was life-saving but the patient developed acute renal failure with late recovery. PMID- 27406289 TI - Machine learning, statistical learning and the future of biological research in psychiatry. AB - Psychiatric research has entered the age of 'Big Data'. Datasets now routinely involve thousands of heterogeneous variables, including clinical, neuroimaging, genomic, proteomic, transcriptomic and other 'omic' measures. The analysis of these datasets is challenging, especially when the number of measurements exceeds the number of individuals, and may be further complicated by missing data for some subjects and variables that are highly correlated. Statistical learning based models are a natural extension of classical statistical approaches but provide more effective methods to analyse very large datasets. In addition, the predictive capability of such models promises to be useful in developing decision support systems. That is, methods that can be introduced to clinical settings and guide, for example, diagnosis classification or personalized treatment. In this review, we aim to outline the potential benefits of statistical learning methods in clinical research. We first introduce the concept of Big Data in different environments. We then describe how modern statistical learning models can be used in practice on Big Datasets to extract relevant information. Finally, we discuss the strengths of using statistical learning in psychiatric studies, from both research and practical clinical points of view. PMID- 27406290 TI - Does therapeutic plasma exchange have a role in the treatment of prosthetic hip associated cobalt toxicity? A case report and literature review. AB - BACKGROUND: Prosthetic hip-associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels. CASE REPORT: A 61-year-old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 ug/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two-thirds of measurable cobalt, but levels rebounded to pre-TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 ug/L and clinical symptoms improved. DISCUSSION: TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment. CONCLUSION: TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated. PMID- 27406291 TI - Phytochemical concentrations and biological activities of Sorghum bicolor alcoholic extracts. AB - Sorghum is an important cereal with reported health benefits. The objectives of this study were to measure the biological activities of alcoholic extracts of ten sorghum varieties and to determine the association between the color of the extracts and their biological activities. Variation on concentrations of bioactives among sorghum varieties was observed with ethanolic extracts giving higher concentrations than methanolic extracts. The color of the extracts significantly correlated with the concentrations of bioactives and with nitric oxide scavenging activity. Freeze-dried ethanol extract is more potent than freeze-dried methanol extract and caused cytotoxicity to A27801AP and PTX-10 OVCA with ED50 values of 0.69 and 1.29 mg mL(-1), respectively. Pre-treatment of OVCA with ethanol extract led to chemosensitization to paclitaxel and the proliferation and colony formation of OVCA cells were reduced by 14.7 to 44.6% and 36.4 to 40.1%, respectively. Sorghum is a potential source of colorants with health promoting properties. This is the first report on the capability of sorghum alcoholic extracts to cause cytotoxicity and chemosensitize ovarian cancer cells in vitro. PMID- 27406292 TI - Editorial for PCCP themed issue "Developments in Density Functional Theory". PMID- 27406293 TI - Editorial. PMID- 27406294 TI - Recent Advances in Bone Marrow Transplantation from Unrelated Volunteer Donors. AB - Marrow transplantation from a phenotypically identical unrelated donor has become a feasible and curative form of treatment for patients with several malignant and nonmalignant disorders who lack an HLA-matched sibling donor. Given the rapid growth of registries of HLA-typed volunteers(-including over 2 million people-)it is now possible to identify a suitable unrelated marrow donor for up to 50% of patients. In this review the recent acquisitions regarding the structure of HLA complex, the new molecular typing technologies and clinical results obtained with unrelated marrow transplants, will be considered. PMID- 27406295 TI - Pathogenesis of Thrombotic Complications of Haematological Malignancies. PMID- 27406296 TI - Haemostatic Abnormalities in Patients with a Clinical Predisposition to Venous Thromboembolism. AB - Although a number of clinical risk factors for deep vein thrombosis (DVT) and embolism are recognised, the precise pathogenetic mechanism operating in the majority of cases is never established. Whilst it is important to recognise congenital deficiencies of naturally occurring anticoagulant proteins, their incidence is often unknown in any given hospitalized population. To examine this controversy, a case controlled study was undertaken to correlate venous thromboembolism at our institution with laboratory tests of haemostasis and to define those having predictive value for this event. Patients with the clinical diagnosis of DVT were divided into those having venographic confirmation (Group 1; n = 106) and a matching series where these studies were negative (Group 2: n = 74). The most frequent associations with DVT were the confirmed diagnosis of severe pulmonary tuberculosis (n = 30), carcinoma (n = 13) and surgery (n = 6); no proven case of a congenital factor deficiency was documented. Comparison of laboratory data from groups 1 and 2 showed, respectively, higher levels of fibrinogen, being 4.6 +/- 0.8 g/L versus 3.16 +/- 1.12 g/L (p < 0.05), fibrin(ogen) degradation products (FDP) of 11.5 +/- 8.3 MUg/ml versus 1.4 +/- 1.63 (p < 0.01), and tissue plasminogen activator antigen (tPA) 26.5 +/- 14.5 versus 12.1 +/- 11.2 (p < 0.01). Decreased levels of several coagulation inhibitory proteins were seen only in association with clinical and haematologic evidence of multisystem disease with coagulopathy. No isolated deficiencies of these proteins were observed, even in the small group of idiopathic recurrent venous thrombosis in this series. Increased plasma fibrinogen, FDP, and plasminogen activator antigen levels may indicate the presence of DVT in individuals at risk, and in the case of pulmonary tuberculosis may be associated with a potential hypercoagulable state. PMID- 27406297 TI - GM-CSF Priming of U937 Monocytic Cells Accelerates, But Does Not Increase, Tissue Factor (TF) Expression or Procoagulant Activity (PCA) After Stimulation with Endotoxin (LPS). AB - The monocytic U937 cell line, though immature, has many properties in common with mature monocytes. We have studied the antigenic expression and activity of tissue factor (TF) in the cytosol and on the surface of U937 cells after exposure to GM CSF and endotoxin (LPS). Following exposure to LPS, both TF phenotype and procoagulant activity (PCA) increased linearly, with peak expression and activity after 18 hours of stimulation. Total PCA (tPCA) increased as early as 6 hours, unlike surface PCA (sPCA) which peaked at 18 hours. A linear correlation was observed between surface TF and both sPCA and tPCA. Incubation of cells with rHuGM-CSF did not effect phenotypic markers of monocyte maturation and had no significant effect on TF expression or PCA. However, cells activated with LPS after rHuGM-CSF priming, demonstrated accelerated expression of TF and PCA, with TF expression peaking at 6 hours and PCA at 2 hours. No increase in the absolute levels of TF were seen after priming with GM-CSF. We conclude that GM-CSF accelerates, but does not increase the magnitude of, the procoagulant response of monocytic cells to endotoxin. We propose that the initial accelerated PCA induction by LPS after rHu-GM-CSF priming, was due to conformational changes in TF and was not due to de novo synthesis of TF protein. PMID- 27406298 TI - The Retinoblastoma Gene in Myeloid Leukaemias. AB - The balance between self-renewal, differentiation and programmed cell death underlies normal haemopoiesis. Disruption of this balance results in leukaemogenesis which is believed to be a multi-step process, culminating in the clonal selection and expansion of an abnormal haemopoietic progenitor cell. The malignant cell clone is believed to have lost the capacity to control cell growth through a series of mutations resulting in the activation of oncogenes and/or inactivation of tumour suppressor genes.(1) These genes are involved in signal transduction, cell proliferation, cell differentiation and cell death or apoptosis. One of the commonly mutated tumour suppressor genes is the retinoblastoma gene (RB1) which is responsible for the childhood tumour, retinoblastoma.(2) Mutations in RB1 leading to inactivation of the retinoblastoma protein, pRB, have also been implicated in many different malignancies including breast cancer, lung cancer and leukaemias.(3-5) The exact role for RB1 mutations in the pathogenesis of these malignancies remains unclear, however there is a strong body of evidence to indicate that inactivation of pRB is a frequent event in a subset of these tumours and has implications for tumour behaviour and disease outcome. PMID- 27406299 TI - Antisense Oligonucleotides: Considerations for Lymphoma Therapy. AB - The majority of lymphomas are of B-cell lineage in origin. Translocations involving the q32 region of chromosome 14, the site of the immunoglobulin heavy chain gene (IGH), are most often observed. Rearrangement of one of the two alleles of this IGH gene is essential for development of the pre-B-cell into a functional B-cell and takes place normally under the influence of a DNA recombinase enzyme system. B-cell lymphomas predominantly involve the deregulation of proto-oncogenes following their juxtaposition to immunoglobulin genes. Their occurrence in part must be due to their obligate DNA breaks and rearrangement within the IG loci and probably involves a mistake mediated by the recombinase enzyme system responsible for normal IG rearrangement.(1,2) The overall result of these changes is a failure of the malignant cell to die in a programmed manner (apoptosis). Conventional treatments are not targeted to these molecular changes and often fail to effect a cure due to an inability to induce apoptosis. Antisense oligonucleotides (ASO) consisting of short sequences of DNA complementary to aberrantly expressed genes in tumours could potentially 'switch off' the inappropriate gene with a consequent antitumour effect by the induction of apoptosis. This represents the underlying basis of antisense therapy in malignant lymphoma. The binding of a sequence-specific oligonucleotide to a targeted length of mRNA occurs with a high level of specificity. Formation of an mRNA-DNA duplex should in theory suppress the translation of the targeted message into protein. If the production of that protein is essential for the survival, or malignant potential, of the cell, then blocking its production will negate the oncogenicity of the cell. Antisense oligonucleotides have been reported to inhibit gene expression as far back as 1978 with the inhibition of the Rous sarcoma virus in transfected chick embryo fibroblasts by a 13-mer oligonucleotide.(3). PMID- 27406300 TI - Acquired Aplasia of the Bone Marrow. AB - Supported by the University of Cape Town Leukaemia Centre and Staff Research (Foote, Becker and Cancer) Fund, the Gwendoline Moore Trust, the Cancer Association of South Africa, the Medical Research Council and the Michael Chanani, Kaliski and M A Richardson Bequests. PMID- 27406301 TI - Iron Deficiency Anemia Associated with an Error of Iron Metabolism in Two Siblings: A Thirty Year Follow Up. AB - For thirty years we have followed two siblings with apparent iron deficiency anemia in the setting of systemic iron overload. This report details their clinical courses, which have been surprisingly disparate. The female sibling has been more severely affected, requiring multiple transfusions. In contrast, the male sibling demonstrated apparent improvement at puberty. Although both have shown evidence of systemic iron overload for many years, neither has had significant end organ toxicity. We discuss the probable pathophysiology of their disorder, drawing from animal models with similar defects in iron uptake and utilization. PMID- 27406302 TI - Activated Cellular Immunity in Chronic Hepatitis C. AB - The importance of local immune mechanisms in the development of chronic hepatitis C and its relation with systemic immune disorders is becoming clear and suggests a more generalized involvement of the immune response in this disease. For this reason, we have investigated the serum concentrations of the soluble immune activation markers neopterin, beta2-microglobulin and interferon-gamma in 28 patients with hepatitis C virus related chronic active hepatitis (n=20) or chronic persistent hepatitis (n=8). Increased levels of neopterin, beta2 microglobulin and interferon-gamma were found in a subgroup of the patients. Serum beta2-microglobulin and neopterin concentrations were strongly related. Patients with chronic active hepatitis had higher beta2-microglobulin levels than those with chronic persistent hepatitis. There were no significant differences in neopterin and interferon-gamma levels between chronic active hepatitis and chronic persistent hepatitis. A strong association was found between older age and higher beta2-microglobulin levels. Because patients with chronic active hepatitis were older than patients with chronic persistent hepatitis, older age may have at least partly contributed to the difference in beta2-microglobulin. Because of the known association between cell-mediated immune activation and the production of interferon-gamma, neopterin and beta32-microglobulin, our results imply that a Th1-type immune response is stimulated in chronic hepatitis C. PMID- 27406303 TI - Kleihauer Testing and Flow Cytometry. A Comparative Study for Assessment of Feto Maternal Haemorrhage. AB - The Kleihauer test has been used world-wide for many years to quantify feto maternal haemorhage, and to ensure that an appropriate dose of anti-D Immunoglobulin (anti-D Ig) is administered both ante-natally and postnatally to RhD negative women to prevent Rh alloimmunisation. Although apparently a simple test to perform, recent reports have suggested that unless meticulous attention is paid to both technique and interpretation, the accuracy of the test cannot be guaranteed. It is suggested that it should be replaced with a flow cytometric test for the presence of fetal RhD positive cells which would give more relevant and accurate results. Flow cytometers are not, however, available to all laboratories performing estimations of feto-matemal haemorrhage (FMH). This study was undertaken to assess the comparability of results obtained using a standardised Kleihauer technique with results obtained using a variety of techniques within hospital laboratories and with flow cytometry. A total of 957 samples were analysed, referring hospitals initially performing a routine Kleihauer test and then forwarding the same sample to the Mersey Transfusion Centre where a standardised Kleihauer test and flow cytometric analysis of FMH were performed. Our results showed that there is variation in Kleihauer results, even when the same sample is used, particularly in quantifying an FMH for which additional anti-D Ig may be required. The tendency however, appears to be to over estimate the size of FMH and administer unnecessary anti-D Ig. Our results suggest that if careful attention is paid to performing a standardised Kleihauer test, then it is of value in estimating the size of FMH, and that flow cytometry may be of additional value for cases in which the Kleihauer result is equivocal or indicates that a large FMH has occurred which requires the administration of additional anti-D Ig. PMID- 27406304 TI - Adult T-Cell Leukaemia-Lymphoma Relapsing as Hodgkin Disease Nodular Sclerosis Subtype. AB - Adult T-cell leukaemia-lymphoma (ATLL) is a distinct disease aetiologically associated with HTLV-I. Hypercalcaemia, organomegaly and a pleomorphic blood picture characterized by the presence of convoluted CD4+CD25+ lymphocytes are the main disease features. We report a patient with a well documented ATLL who relapsed after a long-lasting remission induced by deoxycoformycin treatment. At relapse, the blood picture was consistent with ATLL whereas the histological and immunophenotypical features of the lymph node were indistinguishable from those seen in Hodgkin disease (HD) nodular sclerosis subtype. The monoclonal integration of HTLV-I proviral DNA in the lymph node was demonstrated by Southern blot. The unusual evolution of this case emphasizes the difficulties of differential diagnosis between HD and ATLL with atypical histology and adds new support to the concept of a possible viral participation in a subset of HD cases. PMID- 27406305 TI - Handbook of Blood Transfusion Therapy, 2nd Edition. PMID- 27406306 TI - Do the urolithiasis scoring systems predict the success of percutaneous nephrolithotomy in cases with anatomical abnormalities? AB - The objective of this study is to assess the utility of the Guy, S.T.O.N.E., and CROES nephrolithometry scoring systems (SS), and compare the capability of each system to predict percutaneous nephrolithotomy (PNL) outcome in patients with anatomical abnormalities. We retrospectively collected medical records of patients with anatomical abnormalities who underwent PNL for the treatment of renal calculi by experienced surgical teams in four referral centers. All of the patients were graded by a single observer from each department based on preoperative computed tomography images using each SS. Patient demographics and outcomes were compared according to the complexity of the procedure as graded by each scoring system. A total of 137 cases with anatomical abnormalities [horseshoe kidney (n = 46), malrotation (n = 33), kypho and/or scoliosis (n = 31) and ectopic kidney (n = 27)] were assessed retrospectively. The mean stone burden, number, and density were 708.5 mm2, 1.7, and 791.8 HU, respectively. The mean procedure, fluoroscopy, and hospitalization times were 75.2 +/- 35.3 min, 133.4 +/- 92.3 s, and 3.5 +/- 2.1 days, respectively. Stone-free status was achieved in 106 cases (77.4 %). A total of 17 (13.6 %) complications occurred postoperatively. The mean scores were 2.7, 7.2, and 219.1, for the Guy, S.T.O.N.E., and CROES systems, respectively. CROES score was the independent predictor of PNL success in cases with anatomical abnormalities [p: 0.001, OR 1.01, (95 % CI 1005-1021)]. The CROES scoring system is well correlated with the success of PNL in cases with anatomical abnormalities; the S.T.O.N.E. and Guy scoring systems failed to predict the outcomes of PNL in this specific patient population. PMID- 27406307 TI - Dark fermentation, anaerobic digestion and microbial fuel cells: An integrated system to valorize swine manure and rice bran. AB - This work describes how dark fermentation (DF), anaerobic digestion (AD) and microbial fuel cells (MFC) and solid-liquid separation can be integrated to co produce valuable biochemicals (hydrogen and methane), bioelectricity and biofertilizers. Two integrated systems (System 1: AD+MFC, and System 2: DF+AD+MFC) are described and compared to a traditional one-stage AD system in converting a mixture (COD=124+/-8.1gO2kg(-1)Fresh Matter) of swine manure and rice bran. System 1 gave a biomethane yield of 182 LCH4kg(-1)COD-added, while System 2 gave L yields of bio-hydrogen and bio-methane of 27.3+/-7.2LH2kg(-1)COD added and 154+/-14LCH4kg(-1)COD-added, respectively. A solid-liquid separation (SLS) step was applied to the digested slurry, giving solid and liquid fractions. The liquid fraction was treated via the MFC-steps, showing power densities of 12 13Wm(-3) (500Omega) and average bioelectricity yields of 39.8Whkg(-1)COD to 54.2Whkg(-1)COD. PMID- 27406308 TI - Integrated forward and reverse supply chain: A tire case study. AB - This paper attempts to integrate both a forward and reverse supply chain to design a closed-loop supply chain network (CLSC). The problem in the design of a CLSC network is uncertainty in demand, return products and the quality of return products. Scenario analyses are generated to overcome this uncertainty. In contrast to the existing supply chain network design models, a new application of a CLSC network was studied in this paper to reduce waste. A multi-product, multi tier mixed integer linear model is developed for a CLSC network design. The main objective is to maximize profit and provide waste management decision support in order to minimize pollution. The result shows applicability of the model in the tire industry. The model determines the number and the locations of facilities and the material flows between these facilities. PMID- 27406309 TI - Exploring social dimensions of municipal solid waste management around the globe A systematic literature review. AB - Currently, municipal solid waste (MSW) is experiencing a massive increase in both the amount and composition throughout the world. Effective and efficient MSW management has been widely accepted as an emergent factor for future social development, which requires not only technical innovation, but also the involvement of all stakeholders as well as social, economic, and psychological components. On account of this reality, there is an urgent need for research related to the social dimensions of MSW management. In this paper, a systematic literature review was carried out to characterize and critically evaluate the published literature on the social dimensions of MSW management from 1980 to 2014 in terms of vulnerability, public participation, public attitude and behavior, and policy. A keyword search was first performed by using the Institute for Scientific Information (ISI) Web of Science, which retrieves 1843 documents. After removing the papers that were not closely related to the topic, 200 articles were retained for an in-depth review. In each category, major research issues and observations were summarized, and important insights were obtained. Besides compiling a related list of key references, the analysis results indicate that the global distribution of social dimensions reports on MSW management is inequitable and the research on the social dimensions of MSW management is insufficient, which may attract increased research interest and attention. PMID- 27406310 TI - Characteristics and repair outcome of patients with Vesicovaginal fistula managed in Jimma University teaching Hospital, Ethiopia. AB - BACKGROUND: In Ethiopia, about 9000 fistula cases are estimated to occur every year with an incidence of 2.2/1000 women. This study was aimed to determine obstetric fistula characteristics and surgical repair outcomes among patients with fistula surgical repair. METHODS: A Hospital based cross sectional study design was conducted on all patients with Obstetric vesicovaginal Fistula, who were admitted to Gynecology ward, and had surgical repair from January 2011 to December 2014. Data was collected from patients' chart, operation logbook and discharge logbook which were filled up from the entry of the patient to the hospital till her discharge. At discharge, a dye test was done to determine the outcome of repair. RESULTS: One hundred sixty eight patients with obstetric vesicovaginal fistula were repaired during the study period. The age of the women ranged from 12 to 45 years with mean of 25 (+/-6) years and 10.1 % were younger than 18 years. Eighty percent of patients were laboring for two or more days, 46.4 % delivered abdominally (cesarean section 24.4 %, hysterectomy for uterine rupture 22 %), and 85.7 % ended up in stillbirth. Most patients (56 %) had mid vaginal vesicovaginal fistula. Route of repair was vaginal among 95.8 % of patients, and spinal anesthesia was applied among 70.8 % of patients. Out of 93.4 % patients who had successful closure of their fistula, 84.5 % of patients had their fistula healed and continent, 8.9 % of them developed urinary incontinence while 6.5 % of fistula repair had failed at the time of discharge. CONCLUSIONS: Most fistula patients in this study are older than 18 years, referred from health centers either for cephalopelvic disproportion or obstructed labor after prolonged labor at home. In this study, Spinal anesthesia as well as vaginal route was widely employed and high success rates were achieved with surgical repair. Therefore, increasing access to comprehensive emergency obstetric and new born care is essential to minimize the delay contributing to perinatal mortality and obstetric fistula. In addition use of spinal anesthesia and vaginal route of repair is essential for the high success of repair outcome and low postoperative morbidities. PMID- 27406311 TI - Pythiosis in the Nasal Cavity of Horses. AB - Two cases of nasal pythiosis are reported in horses from the semi-arid region of northeastern Brazil. From January 1986 to December 2015, the Laboratory of Animal Pathology, Federal University of Campina Grande received 830 equine samples, 156 (18.79%) of which were diagnosed with pythiosis. Of these, two horses (1.28%), a male and a female adult cross-breed, had lesions in the nasal cavity. Both horses had access to water reservoirs. Clinically, they had swelling in the rhinofacial region and a serosanguineous nasal discharge. Macroscopically, in case 1, the lesion affected the nasal vestibule, extending to the alar cartilage and nasal septum. In case 2, the lesion extended through the turbinates and the meatuses of the nasal cavity, as well as the ethmoid region. In both cases, the lesions were characterized by having a yellow-grey granular surface with cavitations of different sizes containing coral-like masses of necrotic tissue (kunkers). Histologically, multifocal necrotizing eosinophilic rhinitis associated with hyphae (2-8 MUm) similar to Pythium insidiosum were observed. In case 2, the lesions extended to the muscle, cartilage and bone adjacent to the nasal cavity and lungs. The diagnosis was confirmed by immunohistochemistry. It is concluded that nasal pythiosis occurs sporadically in horses in the semi-arid region of northeastern Brazil where cutaneous pythiosis is prevalent. PMID- 27406312 TI - Swiss Canine Cancer Registry 1955-2008: Occurrence of the Most Common Tumour Diagnoses and Influence of Age, Breed, Body Size, Sex and Neutering Status on Tumour Development. AB - This study is based on the Swiss Canine Cancer Registry, comprising 121,963 diagnostic records of dogs compiled between 1955 and 2008, in which 63,214 (51.83%) animals were diagnosed with tumour lesions through microscopical investigation. Adenoma/adenocarcinoma (n = 12,293, 18.09%) was the most frequent tumour diagnosis. Other common tumour diagnoses were: mast cell tumour (n = 4,415, 6.50%), lymphoma (n = 2,955, 4.35%), melanocytic tumours (n = 2,466, 3.63%), fibroma/fibrosarcoma (n = 2,309, 3.40%), haemangioma/haemangiosarcoma (n = 1,904, 2.80%), squamous cell carcinoma (n = 1,324, 1.95%) and osteoma/osteosarcoma (n = 842, 1.24%). The relative occurrence over time and the most common body locations of those tumour diagnoses are presented. Analyses of the influence of age, breed, body size, sex and neutering status on tumour development were carried out using multiple logistic regression. In certain breeds/breed categories the odds ratios (ORs) for particular tumours were outstandingly high: the boxer had higher ORs for mast cell tumour and haemangioma/haemangiosarcoma, as did the shepherd group for haemangioma/haemangiosarcoma, the schnauzer for squamous cell carcinoma and the rottweiler for osteoma/osteosarcoma. In small dogs, the risk of developing mammary tumours was three times higher than in large dogs. However, small dogs were less likely to be affected by many other tumour types (e.g. tumours of the skeletal system). Examination of the influence of sex and neutering status on tumour prevalence showed that the results depend on the examination method. In all sampling groups the risk for female dogs of developing adenoma/adenocarcinoma was higher than for male dogs. Females had a lower risk of developing haemangioma/haemangiosarcoma and squamous cell carcinoma than males. Neutered animals were at higher risk of developing specific tumours outside the genital organs than intact animals. The sample size allows detailed insight into the influences of age, breed, body size, sex and neutering status on canine tumour development. In many cases, the analysis confirms the findings of other authors. In some cases, the results are unique or contradict other studies, implying that further investigations are necessary. PMID- 27406313 TI - Pharmacological Effects of Capparis spinosa L. AB - Medicinal plants have been known as one of the most important therapeutic agents since ancient times. During the last two decades, much attention has been paid to the health-promoting effects of edible medicinal plants, because of multiple beneficial effects and negligible adverse effects. Capparis spinosa L. is one of the most common medicinal plants, used widely in different parts of the world to treat numerous human diseases. This paper aims to critically review the available scientific literature regarding the health-promoting effects of C. spinosa, its traditional uses, cultivation protocols and phytochemical constituents. Recently, a wide range of evidence has shown that this plant possesses different biological effects, including antioxidant, anticancer and antibacterial effects. Phytochemical analysis shows that C. spinosa has high quantities of bioactive constituents, including polyphenolic compounds, which are responsible for its health-promoting effects, although many of these substances are present in low concentrations and significant changes in their content occur during processing. In addition, there is negligible scientific evidence regarding any adverse effects. Different health promotion activities, as well as tremendous diversity of active constituents, make C. spinosa a good candidate for discovering new drugs. However these findings are still in its infancy and future experimental and clinical studies are needed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406314 TI - Regulatory Single-Nucleotide Variant Predictor Increases Predictive Performance of Functional Regulatory Variants. AB - In silico methods for detecting functionally relevant genetic variants are important for identifying genetic markers of human inherited disease. Much research has focused on protein-coding variants since coding regions have well defined physicochemical and functional properties. However, many bioinformatics tools are not applicable to variants outside coding regions. Here, we increase the classification performance of our regulatory single-nucleotide variant predictor (RSVP) for variants that cause regulatory abnormalities from an AUC of 0.90-0.97 by incorporating genomic regions identified by the ENCODE project into RSVP. RSVP is comparable to a recently published tool, Genome-Wide Annotation of Variants (GWAVA); both RSVP and GWAVA perform better on regulatory variants than a traditional variant predictor, combined annotation-dependent depletion (CADD). However, our method outperforms GWAVA on variants located at similar distances to the transcription start site as the positive set (AUC: 0.96) as compared with GWAVA (AUC: 0.71). Much of this disparity is due to RSVP's incorporation of features pertaining to the nearest gene (expression, GO terms, etc.), which are not included in GWAVA. Our findings hold out the promise of a framework for the assessment of all functional regulatory variants, providing a means to predict which rare or de novo variants are of pathogenic significance. PMID- 27406315 TI - Three-dimensional kinematic adaptations of gait throughout pregnancy and post partum. AB - PURPOSE: The kinematic analysis of gait during pregnancy provides more information about the anatomical changes and contributes to exercise and rehabilitation prescription. The purposes were to describe and quantify the spatial, temporal and kinematic parameters in the joints of the lower limb during gait at the end of the first, second and third trimesters of pregnancy and in the postpartum period. METHODS: A three-dimensional analysis was performed in eleven pregnant women. Repeated measures ANOVA was performed for comparisons between periods. RESULTS: The longitudinal effect of pregnancy was not observed in spatial and temporal parameters. In joint kinematics the effect of pregnancy was observed in all joints for the three planes of motion. The hip joint and pelvis are the structures with more changes, and the results point to an increase in the anterior tilt of the pelvis as the pregnancy progresses, as well as a decrease of the amplitudes of the hip joint. The results suggested that pregnant women need to maintain the stability of the body, and become more efficient in locomotion. CONCLUSIONS: In general, the results retrieve the values from the beginning of pregnancy, indicating that the body was self-organized in order to overcome the morphological and physiological changes which women suffer during pregnancy, indicating that they have the ability to adapt depending on the demands, and after the effect of pregnancy is over, they return to values similar to those found in early pregnancy. PMID- 27406317 TI - Effects of salicylic acid-induced wine rich in anthocyanins on metabolic parameters and adipose insulin signaling in high-fructose fed rats. AB - We evaluated the effects of Syrah red wine treated with salicylic acid (RW SA) and its control red wine (RW) on metabolic parameters, systolic blood pressure and adipose tissue insulin signaling in high-fructose (F) fed rats. Grape treated with SA increased the anthocyanin (ANTs) levels in RW. F induced increased systolic blood pressure, dislipidemia and insulin resistance (HOMA:IR). F rats treated with RW significantly prevented these alterations while RW SA partially attenuated triglycerides levels and HOMA:IR without modifications in HDL cholesterol levels. F impaired the adipose tissue response to insulin. Supplementation with RW and RW SA partially attenuated these alterations. Rats supplemented with RW SA had lesser beneficial effects on metabolic alterations than control RW, while both RW and RW SA attenuated altered adipose response to insulin. More studies are necessary to deeply evaluate the effect on SA-induced RW rich in ANTs levels on metabolic alterations associated to MetS. PMID- 27406318 TI - Temporal correlation between differentiation factor expression and microRNAs in Holstein bovine skeletal muscle. AB - Satellite cells are adult stem cells located between the basal lamina and sarcolemma of muscle fibers. Under physiological conditions, satellite cells are quiescent, but they maintain a strong proliferative potential and propensity to differentiate, which underlies their critical role in muscle preservation and growth. MicroRNAs (miRNAs) play essential roles during animal development as well as in stem cell self-renewal and differentiation regulation. MiRNA-1, miRNA-133a and miRNA-206 are closely related muscle-specific miRNAs, and are thus defined myomiRNAs. MyomiRNAs are integrated into myogenic regulatory networks. Their expression is under the transcriptional and post-transcriptional control of myogenic factors and, in turn, they exhibit widespread control of muscle gene expression. Very little information is available about the regulation and behavior of satellite cells in large farm animals, in particular during satellite cell differentiation. Here, we study bovine satellite cells (BoSCs) undergoing a differentiation process and report the expression pattern of selected genes and miRNAs involved. Muscle samples of longissimus thoracis from Holstein adult male animals were selected for the collection of satellite cells. All satellite cell preparations demonstrated myotube differentiation. To characterize the dynamics of several transcription factors expressed in BoSCs, we performed real-time PCR on complementary DNA generated from the total RNA extracted from BoSCs cultivated in growth medium (GM) or in differentiation medium (DM) for 4 days. In the GM condition, BoSCs expressed the satellite cell lineage markers as well as transcripts for the myogenic regulatory factors. At the time of isolation from muscle, PAX7 was expressed in nearly 100% of BoSCs; however, its messenger RNA (mRNA) levels dramatically decreased between 3 and 6 days post isolation (P<0.01). MyoD mRNA levels increased during the 1st day of cultivation in DM (day 7; P<0.02), showing a gradual activation of the myogenic gene program. During the subsequent 4 days of culture in DM, several tested genes, including MRF4, MYOG, MEF2C, TMEM8C, DES and MYH1, showed increased expression (P<0.05), and these levels remained high throughout the culture period investigated. Meanwhile, the expression of genes involved in the differentiation process also miRNA-1, miRNA 133a and miRNA-206 were strongly up-regulated on the 1st day in DM (day 7; P<0.05). Analysis revealed highly significant correlations between myomiRNAs expression and MEF2C, MRF4, TMEM8C, DES and MYH1 gene expression (P<0.001). Knowledge about the transcriptional changes correlating with the growth and differentiation of skeletal muscle fibers could be helpful for developing strategies to improve production performance in livestock. PMID- 27406319 TI - Topical glycopyrrolate reduces axillary hyperhidrosis. AB - INTRODUCTION: Oral anti-cholinergic medications reduce generalized hyperhidrosis, but the effectiveness of topical anticholinergic solutions on axillary hyperhidrosis is unclear. This study determines the initial effectiveness of 1% and 2% topical glycopyrrolate spray and compares this with Botulinum toxin type A injections for the management of axillary hyperhidrosis. METHODS: In a non randomized, consecutive patient, prospective questionnaire, treatment comparison study, 40 patients with axillary hyperhidrosis were allocated to one of four study groups (10 patients to each group): (a) 1% glycopyrrolate spray, (b) 2% glycopyrrolate spray, (c) subcutaneous Botulinum toxin type A injections, (d) no treatment. Clinical outcomes were measured by comparing a prospectively administered questionnaire, completed both pre-treatment and 6 weeks after starting treatment. Forty healthy volunteers without axillary hyperhidrosis completed the same questionnaire. RESULTS: The three treatment groups showed a significant (P < 0.05) improvement in their hyperhidrosis scores following treatment. The degree of improvement was less for the 1% glycopyrrolate group when compared with the Botulinum toxin type A group (P < 0.05), but there was no difference in treatment outcomes between the 2% glycopyrrolate and Botulinum toxin type A groups. No treatment group experienced reduced hyperhidrosis to a level similar to those without hyperhidrosis. Patients in both, the 2% glycopyrrolate and Botulinum toxin type A groups reported a significant improvement in axillary hyperhidrosis symptoms. These included reduction in psychologically precipitating factors (e.g. public speaking) and axillary hyperhidrosis-specific physical effects (e.g. limitation of clothing choice). CONCLUSIONS: Topical glycopyrrolate spray could provide a further treatment modality to manage axillary hyperhidrosis. PMID- 27406316 TI - A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers. AB - HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism. PMID- 27406320 TI - Modular Fabrication of Polymer Brush Coated Magnetic Nanoparticles: Engineering the Interface for Targeted Cellular Imaging. AB - Development of efficient and rapid protocols for diversification of functional magnetic nanoparticles (MNPs) would enable identification of promising candidates using high-throughput protocols for applications such as diagnostics and cure through early detection and localized delivery. Polymer brush coated magnetic nanoparticles find use in many such applications. A protocol that allows modular diversification of a pool of parent polymer coated nanoparticles will lead to a library of functional materials with improved uniformity. In the present study, polymer brush coated parent magnetic nanoparticles obtained using reversible addition-fragmentation chain transfer (RAFT) polymerization are modified to obtain nanoparticles with different "clickable" groups. In this design, trithiocarbonate group terminated polymer brushes are "grafted from" MNPs using a catechol group bearing initiator. A postpolymerization radical exchange reaction allows installation of "clickable" functional groups like azides and maleimides on the chain ends of the polymers. Thus, modified MNPs can be functionalized using alkyne-containing and thiol-containing moieties like peptides and dyes using the alkyne-azide cycloaddition and the thiol-ene conjugation, respectively. Using the approach outlined here, a cell surface receptor targeting cyclic peptide and a fluorescent dye are attached onto nanoparticle surface. This multifunctional construct allows selective recognition of cancer cells that overexpress integrin receptors. Furthermore, the approach outlined here is not limited to the installation of azide and maleimide functional groups but can be expanded to a variety of "clickable" groups to allow nanoparticle modification using a broad range of chemical conjugations. PMID- 27406321 TI - Correction of Volar Subluxation Deformities of the Metacarpophalangeal Joints Following a Distal Radius Fracture in a Patient With Systemic Lupus Erythematosus. AB - Extensor tendon subluxation over the metacarpal head, leading to metacarpophalangeal joint ulnar deviation, is a hand deformity seen in patients with systemic lupus erythematosus. Apart from soft tissue procedures, metacarpal shortening osteotomy is a previously described surgical treatment for this deformity. We present a patient whose fixed deformity was spontaneously corrected after a displaced distal radius fracture. At 1 year, the correction was maintained. We discuss the biomechanical basis behind the phenomenon. PMID- 27406322 TI - Treatment of Infected Forearm Nonunions With Large Complete Segmental Defects Using Bulk Allograft and Intramedullary Fixation. AB - PURPOSE: The purpose of this study is to report the results of a series of infected forearm nonunions treated from 1998 to 2012 using a staged reconstruction technique. METHODS: At a median of 42 months follow-up, 7 patients who had an average segmental defect of 4.9 cm (range, 2.3-10.4 cm) were available for clinical and radiographic evaluation. Treatment consisted of serial debridement, implantation of an antibiotic cement spacer, and staged reconstruction using a bulk radius or ulna allograft with intramedullary fixation. RESULTS: All 7 patients ultimately achieved solid bone union, although 4 patients (57%) required additional surgery, consisting of autologous bone grafting and plating, to achieve healing at 1 of the allograft-host junction sites. No patient had recurrence of infection, and all reported substantial improvement with increased function and decreased pain. CONCLUSIONS: Our approach ultimately resulted in a 100% union rate without recurrence of infection, although many patients may require additional surgery to attain healing at both allograft-junction sites. Using bulk allograft provides the ability to span a large defect while reconstituting the forearm anatomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V. PMID- 27406323 TI - Dorsal Approach Decreases Operative Time for Complex Metacarpophalangeal Dislocations. AB - PURPOSE: Complex metacarpophalangeal (MCP) dislocations require open surgical reduction, but surgeons disagree about the best surgical approach. We hypothesized that a dorsal approach would require less operative time than would a volar approach and result in a decreased need for a secondary approach. METHODS: We performed a retrospective chart review of all isolated irreducible dorsal MCP dislocations treated at 2 level 1 trauma centers between 2005 and 2015. We recorded the initial surgical approach (volar or dorsal), total operative time, and whether the surgeon used a second surgical approach. Operative times for initial volar approach versus initial dorsal approach, hand surgeon versus non-hand surgeon, and thumb versus other digits were compared using the 2-tailed Student t test. We used Fisher exact test to compare the need for a second approach between the volar and dorsal approach groups. RESULTS: A total of 21 patients (22 digits) with MCP dislocations required surgical reduction. Average operative time was longer for the 14 patients who underwent the initial volar approach (70 minutes) than for the 7 who underwent an initial dorsal approach (45 minutes). Six of the 14 MCP joints approached volarly (42%) required a second dorsal approach. None of the 7 patients in the dorsal group required a second approach. CONCLUSIONS: Using a dorsal approach to reduce complex MCP dislocations reduces operative time and decreases the need for a secondary approach. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 27406324 TI - Identification of microbes from the surfaces of food-processing lines based on the flow cytometric evaluation of cellular metabolic activity combined with cell sorting. AB - In this study the design of a flow cytometry-based procedure to facilitate the detection of adherent bacteria from food-processing surfaces was evaluated. The measurement of the cellular redox potential (CRP) of microbial cells was combined with cell sorting for the identification of microorganisms. The procedure enhanced live/dead cell discrimination owing to the measurement of the cell physiology. The microbial contamination of the surface of a stainless steel conveyor used to process button mushrooms was evaluated in three independent experiments. The flow cytometry procedure provided a step towards monitoring of contamination and enabled the assessment of microbial food safety hazards by the discrimination of active, mid-active and non-active bacterial sub-populations based on determination of their cellular vitality and subsequently single cell sorting to isolate microbial strains from discriminated sub-populations. There was a significant correlation (r = 0.97; p < 0.05) between the bacterial cell count estimated by the pour plate method and flow cytometry, despite there being differences in the absolute number of cells detected. The combined approach of flow cytometric CRP measurement and cell sorting allowed an in situ analysis of microbial cell vitality and the identification of species from defined sub populations, although the identified microbes were limited to culturable cells. PMID- 27406325 TI - Assessing the Climate Trade-Offs of Gasoline Direct Injection Engines. AB - Compared to port fuel injection (PFI) engine exhaust, gasoline direct injection (GDI) engine exhaust has higher emissions of black carbon (BC), a climate-warming pollutant. However, the relative increase in BC emissions and climate trade-offs of replacing PFI vehicles with more fuel efficient GDI vehicles remain uncertain. In this study, BC emissions from GDI and PFI vehicles were compiled and BC emissions scenarios were developed to evaluate the climate impact of GDI vehicles using global warming potential (GWP) and global temperature potential (GTP) metrics. From a 20 year time horizon GWP analysis, average fuel economy improvements ranging from 0.14 to 14% with GDI vehicles are required to offset BC induced warming. For all but the lowest BC scenario, installing a gasoline particulate filter with an 80% BC removal efficiency and <1% fuel penalty is climate beneficial. From the GTP-based analysis, it was also determined that GDI vehicles are climate beneficial within <1-20 years; longer time horizons were associated with higher BC scenarios. The GDI BC emissions spanned 2 orders of magnitude and varied by ambient temperature, engine operation, and fuel composition. More work is needed to understand BC formation mechanisms in GDI engines to ensure that the climate impacts of this engine technology are minimal. PMID- 27406327 TI - Differential Adhesion Selection for Enrichment of Tendon-Derived Progenitor Cells During In Vitro Culture. AB - Preplating, a technique used to separate rapidly adherent fibroblasts from the less-adherent progenitor cells, has been used successfully to isolate skeletal muscle-derived stem cells. The objective of this study was to determine if preplating could also be applied to enrich tendon-derived progenitor cells (TDPCs) before monolayer expansion. Cell suspensions obtained by collagenase digestion of equine lateral digital extensor tendon were serially transferred into adherent plates every 12 h for 4 days. TDPC fractions obtained from initial (TPP0), third (TPP3), and seventh (TPP7) preplate were passaged twice and used for subsequent analyses. Growth/proliferation and basal tenogenic gene expression of the three TDPC fractions were largely similar. Preplating and subsequent monolayer expansion did not alter the immunophenotype (CD29(+), CD44(+), CD90(+), and CD45(-)) and trilineage differentiation capacity of TDPC fractions. Overall, TDPCs were robustly osteogenic, but exhibited comparatively weak adipogenic and chondrogenic capacities. These outcomes indicate that preplating does not enrich for tendon-derived progenitors during in vitro culture, and "whole tendon digest" derived cells are as appropriate for cell-based therapies. PMID- 27406326 TI - Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake. AB - KEY POINTS: Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3 sulfate primarily affects acinar cells. Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+ ; and Na+ -dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells. Bile acid-mediated pancreatic damage can be further escalated by bradykinin-induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. ABSTRACT: Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na+ -dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca2+ and significantly reduced in the absence of Na+ , showing that bile-dependent cell death was a downstream event of Ca2+ signals. Finally, combined application of TLC-S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC-S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells. PMID- 27406328 TI - Germline replacement by blastula cell transplantation in the fish medaka. AB - Primordial germ cell (PGC) specification early in development establishes the germline for reproduction and reproductive technologies. Germline replacement (GR) is a powerful tool for conservation of valuable or endangered animals. GR is achievable by germ cell transplantation into the PGC migration pathway or gonads. Blastula cell transplantation (BCT) can also lead to the chimeric germline containing PGCs of both donor and host origins. It has remained largely unknown whether BCT is able to achieve GR at a high efficiency. Here we report efficient GR by BCT into blastula embryos in the fish medaka (Oryzias latipes). Specifically, dnd depletion completely ablated host PGCs and fertility, and dnd overexpression remarkably boosted PGCs in donor blastulae. BCT between normal donor and host produced a germline transmission rate of ~4%. This rate was enhanced up to ~30% upon PGC boosting in donors. Most importantly, BCT between PGC-boosted donors and PGC-ablated hosts led to more than 90% fertility restoration and 100% GR. Therefore, BCT features an extremely high efficiency of fertility recovery and GR in medaka. This finding makes medaka an ideal model to analyze genetic and physiological donor-host compatibilities for BCT-mediated surrogate production and propagation of endangered lower vertebrates and biodiversity. PMID- 27406330 TI - Complexity of occupational exposures for home health-care workers: nurses vs. home health aides. AB - AIM: To identify occupational exposures for home health-care nurses and aides. BACKGROUND: Home health-care workers' occupational injury rates in the USA are higher than the national average, yet research on causative exposures and hazards is limited. METHODS: Participants were interviewed about annual frequency of occupational exposures and hazards. Exposure and hazard means were compared between home health-care nurses and aides using a Wilcoxon two-sample test. RESULTS: A majority of the sample was over 40 years old and obese, potentially increasing injury risks. Home health-care nurses performed more clinical tasks, increasing exposure to blood-borne pathogens. Home health-care aides performed more physical tasks with risk for occupational musculoskeletal injuries. They also dispensed oral medications and anti-cancer medications, and were exposed to drug residue at a frequency comparable to home health-care nurses. Both groups were exposed to occupational second-hand smoke. CONCLUSIONS: Establishing employee safety-related policies, promoting healthy lifestyle among staff, and making engineered tools readily available to staff can assist in decreasing exposures and hazards. IMPLICATIONS FOR NURSING MANAGEMENT: Implications for nursing management include implementation of health-promotion programmes, strategies to reduce exposure to second-hand smoke, ensuring access to and education on assistive and safety devices, and education for all staff on protection against drug residue. PMID- 27406331 TI - Vitamin E Status and Neurodegenerative Disease. AB - Vitamin E (alpha-and gamma-tocopherol) may slow the progression of a number of major degenerative diseases of the nervous system that appear to be significantly worsened by oxidative stress. The effects of vitamin E on excitoxicity in cultured neurones is considered, together with ataxia due to vitamin E deficiency (AVED) arising from abetalipoproteinaemia, cholestatic liver disease, cystic fibrosis, short bowel syndrome, total parenteral nutrition, diabetic peripheral neuropathy and familial isolated vitamin E (FIVE) deficiency. Selenium deficiency in Keshan disease is also described in relation to the cardiomyopathy seen in Friedreich's ataxia. Evidence for any beneficial effects of vitamin E upon the course of Friedreich's ataxia, tardive dyskinesia, amyotrophic lateral sclerosis (motor neurone disease), Parkinson's disease, Alzheimer's disease, and Huntington's disease is examined. The application of vitamin E derivatives as protective agents in posttraumatic injury to the nervous system (stroke, head and spinal cord injury and haemorrhage) is discussed. PMID- 27406332 TI - Effect of Neuropeptide Y Injected into the Hypothalamic Suprachiasmatic Nucleus or the Lateral Cerebral Ventricle on Food Intake. AB - The effects of neuropeptide Y (NPY) injected into the hypothalamic suprachiasmatic nucleus (SCN) or the lateral cerebral ventricle (LCV) at four different time points of the day on the subsequent 2h food intake from three macronutrient rich diets were examined. Adult Wistar male rats on 12-12 h light dark cycles received either saline or NPY (lOOpmol) through chronically implanted guide cannulas into the SCN or the LCV. The results show that NPY was effective at stimulating energy intake from the dextrin/sucrose diet when injected in the SCN after lights-on, and total energy intake when injected in the LCV before and after lights-on. This suggests that NPY is effective at altering nychthemeral variations in total energy and energy from dextrin/sucrose diets, but this modulation is specific to the site of administration. PMID- 27406329 TI - Glycyrrhetinic acid protects H9c2 cells from oxygen glucose deprivation-induced injury through the PI3K/AKt signaling pathway. AB - Glycyrrhetinic acid (GA) is an ingredient of triterpene saponins found in Gancao (Radix Glycyrrhizae). Here, we investigated the protective effects of GA in H9c2 cells, and explored its possible mechanism of action. Different concentrations of GA were used to treat H9c2 cells under oxygen glucose deprivation. We analyzed cell necrosis and apoptosis using optical microscopy, Hoechst 33342 staining, FITC-annexin V/PI double-staining and lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and interleukin (IL)-1beta assays. Changes in related pro apoptosis and anti-apoptosis proteins were detected by Western blot. Optical microscopy showed that GA improved cell morphology, including cell shrinkage, cauliflower-like membrane blebbing, and even some cell debris. Meanwhile, GA also ameliorated cell nuclei characteristics such as nucleus size, chromatin condensation and bright staining from Hoechst 33342 staining. GA also lowered the apoptotic rate and the levels of LDH, CK-MB and IL-1beta in a dose-dependent manner. Furthermore, GA treatment increased Bcl-2 protein expression and decreased caspase-8 and Bax protein expression, while elevating the Bcl-2/Bax ratio. GA preconditioning increased p-AKt protein expression; however, after adding LY 294002, the p-AKt expression decreased obviously. Our results demonstrated that GA could protect H9c2 cells from apoptosis in a dose-dependent manner, and the potential mechanism might be related to the PI3K/AKt signaling pathway. PMID- 27406333 TI - Endogenous Enterostatin, Proteases, and Dietary Fat Preference in Rats. AB - Many studies clearly demonstrate inhibition of dietary fat preference by exogenous enterostatins in rodents. However, what role endogenous enterostatin, if any, may play in the regulation of fat intake is not clear. To this end, we examined whether there is a relationship between plasma enterostatin (VPDPR)-like immunoreactivity and fat preference. Additionally, since enterostatin is a product of tryptic cleavage of procolipase, we examined the effect of camostat, a protease inhibitor known to inhibit trypsin and other proteases, on dietary fat preference and plasma enterostatin concentration. The results of these studies show that while there was a significant inverse relationship between plasma enterostatin and fat preference, the effect of camostat on fat preference or plasma enterostatin concentration was not clear. PMID- 27406334 TI - Dietary Sucrose Lowers Nociceptive Latencies Independently of Thermogenic Effects. AB - Previous reports indicate that chronic sucrose feeding produces a significant reduction in the latency of response in the radiant heat tail-flick test. Other earlier studies have shown a relationship between tail-skin temperature and tail flick latency, while others yet have shown an increase in tail-skin temperature following sucrose feeding. Together these previous findings suggest the possibility that dietary-induced alterations in nociceptive latencies occur as an artifact secondary to diet-related changes in tail-skin temperature. The data presented in this study show that chronic sucrose feeding significantly increased tail-skin temperature (p < 0.0001) and decreased tail-flick latency (p < 0.0001) with significant correlations between tail-skin temperatures and tail-flick latencies in both the control and sucrose fed groups. However, while the slopes of the regression lines were similar for both groups, the elevations of the lines were significantly different (p = 0.0068) suggesting a dietary impact on nociceptive thresholds independent of the temperature effect. The data were also subjected to a previously reported temperature-correction procedure and comparisons in the methods of data analysis are discussed. PMID- 27406335 TI - Responses to Indispensable Amino Acid Deficiency and Replenishment Recorded in the Anterior Piriform Cortex of the Behaving Rat. AB - The anterior piriform cortex (APC) may house the sensor for essential amino acid homeostasis in the brain. Several lines of evidence suggest that the APC is activated shortly after ingestion of an amino acid deficient diet. We examined the averaged evoked potentials elicited in the APC by stimulation of the lateral olfactory tract, in awake, behaving rats before and after feeding basal (BAS), threonine devoid (DEV), or corrected (COR) diets to determine directly whether the APC is activated after eating a DEV diet. When fed the DEV diet, the absolute values for the amplitude of the first negative wave differed by 36.8 +/- 5.8% (P<= 0.005) from that seen after eating the BAS diet. The latency to the second negative wave was altered by 17.2 +/- 3.7% (P <= 0.02) compared with BAS. These results were seen by 3 h after introduction of the diet, and show that the APC is indeed activated after ingestion of a DEV diet. Also, the responses to COR returned to BAS levels by 3 h. This supports the hypothesis that the APC is important both for rejection of the DEV diet and for the recognition of the replenishment of the limiting amino acid by the COR diet. PMID- 27406336 TI - Monothiols and Vitamins are Ideal Therapeutic Agents for Mercury Elimination from Nervous and Non-Nervous Tissues of Fish. AB - Use of mercury and its compounds in various industries and agriculture is increasing its concentration in aquatic environment and affecting the organisms living therein. Among these, the fishes are commercially important for humans as an important source of protein. The fish meat transfers good amount of mercury to man, therefore, its elimination is quit essential both from fishes and the consumers. As a step in this direction, the present study has been designed to detoxify the fishes from mercury. For this purpose a freshwater fish (Channa punctatus) was treated with mercuric chloride (0.5 ppm) for 96 h and thereafter, detoxicated with vitamin B complex, glutathione and N-acetyl-DL-homocysteine thiolactone used either alone or in various combinations for another 96 h. One group of 96-h mercury treated animals were kept in tap water and sacrificed after 192 h. This group was considered as mercury washed group and it served as control to all therapeutic groups. Mercury treated fish showed a highest concentration of the metal in kidney followed by liver, gills, brain and muscles. In mercury washed group, metal was removed significantly from all the non-nervous tissues, but in brain about 52% further increase was observed. The results obtained from theraputic studies were quite exciting as 50-80% mercury was mobilized from all tissues including brain within 96 h of treatment. PMID- 27406337 TI - Fasting- and Feeding-associated Changes in Enterostatin (Val-Pro-Asp-Pro-Arg) like Immunoreactivity in the Rat Brain. AB - Enterostatin (Val-Pro-Asp-Pro-Arg)-like immunoreactivity (VPDPR-LI) is unevenly distributed in the rat brain, with the highest concentration in the striatum. Fasting elevates the level of VPDPR-LI in the striatum but not in other regions of the rat brain. When fasted rats were fed, however, the striatal VPDPR-LI returns to the control (fed ad lib) level. These results, coupled with the anorectic properties of enterostatin, suggest an appetite regulatory role for endogenous VPDPR-LI in the rat. PMID- 27406338 TI - Computational Electrocardiography: Revisiting Holter ECG Monitoring. AB - BACKGROUND: Since 1942, when Goldberger introduced the 12-lead electrocardiography (ECG), this diagnostic method has not been changed. OBJECTIVES: After 70 years of technologic developments, we revisit Holter ECG from recording to understanding. METHODS: A fundamental change is fore-seen towards "computational ECG" (CECG), where continuous monitoring is producing big data volumes that are impossible to be inspected conventionally but require efficient computational methods. We draw parallels between CECG and computational biology, in particular with respect to computed tomography, computed radiology, and computed photography. From that, we identify technology and methodology needed for CECG. RESULTS: Real-time transfer of raw data into meaningful parameters that are tracked over time will allow prediction of serious events, such as sudden cardiac death. Evolved from Holter's technology, portable smartphones with Bluetooth-connected textile-embedded sensors will capture noisy raw data (recording), process meaningful parameters over time (analysis), and transfer them to cloud services for sharing (handling), predicting serious events, and alarming (understanding). To make this happen, the following fields need more research: i) signal processing, ii) cycle decomposition; iii) cycle normalization, iv) cycle modeling, v) clinical parameter computation, vi) physiological modeling, and vii) event prediction. CONCLUSIONS: We shall start immediately developing methodology for CECG analysis and understanding. PMID- 27406339 TI - Developmental Validation of a novel 5 dye Y-STR System comprising the 27 YfilerPlus loci. AB - In this study, a new STRtyper-27 system, including the same Yfiler Plus loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, Y-GATA H4, DYS449, DYS460, DYS481, DYS518, DYS533, DYS570, DYS576, DYS627 and DYF387S1a/b), was established using a set of 5 fluorescent dye labels. Primers, internal size standard, allelic ladders and matrix standard set were designed and created in-house for this multiplex system. This paper describes the validation studies conducted with the STRtyper-27Y system using a 3130XL genetic analyzer for fragment length detection that included the analysis of the following parameters and aspects: sensitivity, species specificity, inhibition, haplotype concordance, precision, stutter, DNA mixtures, and stability studies with crime scene samples. The studies demonstrated, that the STRtyper-27Y system provided equivalent overall performance comparable to the latest Yfiler Plus kit, but with enhanced compatibility in terms of instrument platforms and software allowing forensic laboratories to conduct its forensic application and evaluate its performance, all in their own 5 dye Y-STR chemistry system /environment without software or instrument upgrades. PMID- 27406340 TI - Coarsening behaviour of M23C6 carbides in creep-resistant steel exposed to high temperatures. AB - High operating temperatures can have very deleterious effects on the long-term performance of high-Cr, creep-resistant steels used, for example, in the structural components of power plants. For the popular creep-resistant steel X20CrMoV12.1 we analysed the processes of carbide growth using a variety of analytical techniques: transmission electron microscopy (TEM) and diffraction (TED), scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD). The evolution of the microstructure after different aging times was the basis for a much better understanding of the boundary-migration processes and the growth of the carbides. We present an explanation as to why some locations are preferential for this growth, and using EBSD we were able to define the proper orientational relationship between the carbides and the matrix. PMID- 27406341 TI - Physical role for the nucleus in cell migration. AB - Cell migration is important for the function of many eukaryotic cells. Recently the nucleus has been shown to play an important role in cell motility. After giving an overview of cell motility mechanisms we review what is currently known about the mechanical properties of the nucleus and the connections between it and the cytoskeleton. We also discuss connections to the extracellular matrix and mechanotransduction. We identify key physical roles of the nucleus in cell migration. PMID- 27406342 TI - Unravelling the community structure of the climate system by using lags and symbolic time-series analysis. AB - Many natural systems can be represented by complex networks of dynamical units with modular structure in the form of communities of densely interconnected nodes. Unraveling this community structure from observed data requires the development of appropriate tools, particularly when the nodes are embedded in a regular space grid and the datasets are short and noisy. Here we propose two methods to identify communities, and validate them with the analysis of climate datasets recorded at a regular grid of geographical locations covering the Earth surface. By identifying mutual lags among time-series recorded at different grid points, and by applying symbolic time-series analysis, we are able to extract meaningful regional communities, which can be interpreted in terms of large-scale climate phenomena. The methods proposed here are valuable tools for the study of other systems represented by networks of dynamical units, allowing the identification of communities, through time-series analysis of the observed output signals. PMID- 27406343 TI - Preparation, characterization and luminescence properties of a new hydrous red phosphor CaB3 O5 (OH):Eu3+ with different morphologies. AB - A new borate phosphor CaB3 O5 (OH):Eu3+ with different morphologies was synthesized using a hydrothermal method and its luminescence properties were studied. The effects of surfactants on the crystal structures, morphologies and luminescence properties of the samples were studied. The results showed that the surfactants play an important role in controlling the morphology and improving the luminescence properties of phosphors. The luminescence intensity and R/O(I615/I592) value were enhanced for the prepared sample by adding PEG4000. The prepared sample exhibited a higher R/O than some anhydrous calcium borate phosphors, indicating that this product could serve as a new potential red phosphor. PMID- 27406345 TI - I-SPY 2--A Glimpse of the Future of Phase 2 Drug Development? PMID- 27406344 TI - Dabigatran exhibits low intensity of left atrial spontaneous echo contrast in patients with nonvalvular atrial fibrillation as compared with warfarin. AB - The presence of spontaneous echo contrast (SEC) in the left atrium has been reported to be an independent predictor of thromboembolic risk in patients with atrial fibrillation (AF). Dabigatran was associated with lower rates of stroke and systemic embolism as compared with warfarin when administered at a higher dose. Between July 2011 and October 2015, nonvalvular AF patients treated with warfarin or dabigatran who had transesophageal echocardiography prior to ablation therapy for AF were enrolled. The intensity of SEC was classified into four grades, from 0 to 3. Univariate and multivariate analysis was performed to analyze factors associated with SEC. Sixty-five patients were on dabigatran and 65 were on warfarin, with the prothrombin time in therapeutic range. There were no significant differences in the age, CHADS2 score, left atrial dimension, and left atrial appendage flow between the two groups. However, there were more grade 2 or higher patients with left atrial SEC in the warfarin group (n = 20) than in the dabigatran group (n = 2) (p < 0.001). When multivariate regression analysis was performed, grade 2 or higher left atrial SEC was independently associated with no dabigatran usage in addition to high brain natriuretic peptide level and high incidence of diabetes mellitus or persistent AF. Thus, dabigatran exhibited low intensity of left atrial SEC in nonvalvular AF patients as compared with warfarin. PMID- 27406348 TI - CLINICAL PRACTICE. Polycystic Ovary Syndrome. PMID- 27406349 TI - Adaptive Designs for Clinical Trials. PMID- 27406350 TI - IMAGES IN CLINICAL MEDICINE. Eyelid Melanoma. PMID- 27406351 TI - CLINICAL PROBLEM-SOLVING. A Bruising Loss. PMID- 27406352 TI - I-SPY 2--Toward More Rapid Progress in Breast Cancer Treatment. PMID- 27406353 TI - Corralling Colonic Flagellated Microbiota. PMID- 27406354 TI - Testosterone Treatment in Older Men. PMID- 27406346 TI - Adaptive Randomization of Neratinib in Early Breast Cancer. AB - BACKGROUND: The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). METHODS: We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. RESULTS: Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone receptor-negative signature. Among patients with HER2-positive, hormone-receptor negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%. CONCLUSIONS: Neratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.). PMID- 27406355 TI - Testosterone Treatment in Older Men. PMID- 27406356 TI - Testosterone Treatment in Older Men. PMID- 27406357 TI - Testosterone Treatment in Older Men. PMID- 27406358 TI - Testosterone Treatment in Older Men. PMID- 27406347 TI - Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. AB - BACKGROUND: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. METHODS: In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. RESULTS: With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. CONCLUSIONS: The process used in our trial showed that veliparib carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.). PMID- 27406359 TI - Aspirin before Coronary Artery Surgery. PMID- 27406360 TI - Aspirin before Coronary Artery Surgery. PMID- 27406361 TI - Aspirin before Coronary Artery Surgery. PMID- 27406362 TI - Incidence of Dementia over Three Decades in the Framingham Heart Study. PMID- 27406363 TI - Incidence of Dementia over Three Decades in the Framingham Heart Study. PMID- 27406364 TI - Incidence of Dementia over Three Decades in the Framingham Heart Study. PMID- 27406365 TI - Vibratory Urticaria and ADGRE2. PMID- 27406366 TI - Vibratory Urticaria and ADGRE2. PMID- 27406367 TI - Mitigation Strategies for Opioid Abuse. PMID- 27406368 TI - Mitigation Strategies for Opioid Abuse. PMID- 27406369 TI - Mitigation Strategies for Opioid Abuse. PMID- 27406370 TI - Platelet Transfusions in Acute Leukemia. PMID- 27406371 TI - Copy-Number Variation and False Positive Prenatal Screening Results. PMID- 27406372 TI - IMAGES IN CLINICAL MEDICINE. Dubin-Johnson Syndrome. PMID- 27406373 TI - Glycerolipid synthesis and lipid trafficking in plant mitochondria. AB - Lipid trafficking between mitochondria and other organelles is required for mitochondrial membrane biogenesis and signaling. This lipid exchange occurs by poorly understood nonvesicular mechanisms. In yeast and mammalian cells, this lipid exchange is thought to take place at contact sites between mitochondria and the ER or vacuolar membranes. Some proteins involved in the tethering between membranes or in the transfer of lipids in mitochondria have been identified. However, in plants, little is known about the synthesis of mitochondrial membranes. Mitochondrial membrane biogenesis is particularly important and noteworthy in plants as the lipid composition of mitochondrial membranes is dramatically changed during phosphate starvation and other stresses. This review focuses on the principal pathways involved in the synthesis of the most abundant mitochondrial glycerolipids in plants and the lipid trafficking that is required for plant mitochondria membrane biogenesis. PMID- 27406376 TI - Value of automatic patient motion detection and correction in myocardial perfusion imaging using a CZT-based SPECT camera. AB - BACKGROUND: Correction of motion has become feasible on cadmium-zinc-telluride (CZT)-based SPECT cameras during myocardial perfusion imaging (MPI). Our aim was to quantify the motion and to determine the value of automatic correction using commercially available software. METHODS AND RESULTS: We retrospectively included 83 consecutive patients who underwent stress-rest MPI CZT-SPECT and invasive fractional flow reserve (FFR) measurement. Eight-minute stress acquisitions were reformatted into 1.0- and 20-second bins to detect respiratory motion (RM) and patient motion (PM), respectively. RM and PM were quantified and scans were automatically corrected. Total perfusion deficit (TPD) and SPECT interpretation normal, equivocal, or abnormal-were compared between the noncorrected and corrected scans. Scans with a changed SPECT interpretation were compared with FFR, the reference standard. Average RM was 2.5 +/- 0.4 mm and maximal PM was 4.5 +/- 1.3 mm. RM correction influenced the diagnostic outcomes in two patients based on TPD changes >=7% and in nine patients based on changed visual interpretation. In only four of these patients, the changed SPECT interpretation corresponded with FFR measurements. Correction for PM did not influence the diagnostic outcomes. CONCLUSION: Respiratory motion and patient motion were small. Motion correction did not appear to improve the diagnostic outcome and, hence, the added value seems limited in MPI using CZT-based SPECT cameras. PMID- 27406374 TI - Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy. AB - Hand, foot, and mouth disease (HFMD) is a contagious viral disease and mainly affects infants and young children. The main manifestations are fever, vesicular rashes on hand, feet and buttocks and ulcers in the oral mucosa. Usually, HFMD is self-limiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis and neurorespiratory syndrome. Historically, outbreaks of HFMD were mainly caused by two enteroviruses: the coxsackievirus A16 (CV-A16) and the enterovirus 71 (EV A71). In the recent years, coxsackievirus A6 and coxsackievirus A10 have been widely associated with both sporadic cases and outbreaks of HFMD worldwide, particularly in India, South East Asia and Europe with an increased frequency of neurological complications as well as mortality. Currently, there is no pharmacological intervention or vaccine available for HFMD. A formalin inactivated EV-A71 vaccine has completed clinical trial in several Asian countries. However, this vaccine cannot protect against other major emerging etiologies of HFMD such as CV-A16, CV-A6 and CV-A10. Therefore, the development of a globally representative multivalent HFMD vaccine could be the best strategy. PMID- 27406377 TI - Ventricular arrhythmias in chronic Chagas cardiomyopathy: Can studying myocardial sympathetic denervation provide the answers? PMID- 27406378 TI - Treat to target in systemic lupus erythematosus: a commentary. AB - Treat to target (T2T) strategies have proved to be useful in several chronic disorders, including Rheumatoid Arthritis. In systemic lupus erythematosus (SLE), T2T strategy has been proposed in order to control disease activity, improve health-related quality of life, and reduce morbidity and mortality. Remission would be the main target, but a low disease activity state (LDAS) could be an acceptable alternative. However, due to SLE protean manifestations, the operational definitions of both remission and LDAS are still in progress. The definitions of these targets, remission and LDAS, should include a validated disease activity index, the treatments allowed, and the minimum length of time the target should be maintained. Furthermore, achieving these targets should result in better disease outcomes such as reducing damage accrual. This review addresses the current state regarding these possible targets in SLE and the impact of achieving them in intermediate and long-term outcomes of this disease. PMID- 27406375 TI - Early and mid-term outcomes of 1904 patients undergoing transcatheter balloon expandable valve implantation in Italy: results from the Italian Transcatheter Balloon-Expandable Valve Implantation Registry (ITER). AB - OBJECTIVES: The aim of this multicentre study is to report the clinical experiences of all patients undergoing transcatheter aortic valve implantation (TAVI) with a balloon-expandable device in Italy. METHODS: The Italian Transcatheter balloon-Expandable valve Registry (ITER) is a real-world registry that includes patients who have undergone TAVI with the Sapien (Edwards Lifesciences, Irvine, CA, USA) bioprosthesis in Italy since it became available in clinical practice. From 2007 to 2012, 1904 patients were enrolled to undergo TAVI in 33 Italian centres. Outcomes were classified according to the updated Valve Academic Research Consortium (VARC-2) definitions. A multivariable analysis was performed to identify independent predictors of all-cause mortality. RESULTS: Mean age was 81.7 (SD:6.2) years, and 1147 (60.2%) patients were female. Mean Logistic EuroSCORE was 21.1% (SD:13.7). Transfemoral, transapical, transaortic and transaxillary TAVI was performed in 1252 (65.8%), 630 (33.1%), 18 (0.9%) and 4 (0.2%) patients, respectively. Operative mortality was 7.2% (137 patients). The VARC-2 outcomes were as follows: device success, 88.1%; disabling stroke, 1.0%; life-threatening and major bleeding 9.8 and 10.5%, respectively; major vascular complication, 9.7%; acute kidney injury, 8.2%; acute myocardial infarction <=72 h, 1.5%. Perioperative pacemaker implantation was necessary in 116 (6.1%) patients. At discharge, the mean transprosthetic gradient was 10.7 (SD:4.5) mmHg. Incidence of postoperative mild, moderate or severe paravalvular leak was, respectively, 32.1, 5.0 and 0.4%. A total of 444/1767 (25.1%) deaths after hospital discharge were reported: of these, 168 (37.8%) were classified as cardiac death. Preoperative independent predictors of all-cause mortality were male gender (HR: 1.395; 95% CI:1.052-1.849); overweight, BMI 25-30 kg/m2 (HR: 0.775; 95% CI: 0.616-0.974); serum creatinine level (every 1 mg/dl increase; HR: 1.314; 95% CI:1.167-1.480); haemoglobin level (every 1 g/dl increase; HR: 0.905; 95% CI:0.833-0.984); critical preoperative state (HR: 2.282; 95% CI: 1.384 3.761); neurological dysfunction (HR: 1.552; 95% CI:1.060-2.272); atrial fibrillation (HR: 1.556; 95% CI:1.213-1.995); pacemaker rhythm (HR: 1.948; 95% CI:1.310-2.896); NYHA Class III or IV (HR: 1.800; 95% CI:1.205-2.689 or HR: 2.331; 95% CI:1.392-3.903, respectively). CONCLUSIONS: TAVI with a balloon expandable device in the 'real world' shows good mid-term outcomes in terms of survival, technical success, valve-related adverse events and haemodynamic performance. PMID- 27406379 TI - Different patterns of extracellular proteolytic activity in W303a and BY4742 Saccharomyces cerevisiae strains. AB - Protease secretion in Saccharomyces cerevisiae cultures is a complex process, important for the application of this organism in the food industry and biotechnology. Previous studies provide rather quantitative data, yielding no information about the number of enzymes involved in proteolysis and their individual biochemical properties. Here we demonstrate that W303a and BY4742 S. cerevisiae strains reveal different patterns of spontaneous and gelatin-induced extracellular proteolytic activity. We applied the gelatin zymography assay to track changes of the proteolytic profile in time, finding the protease secretion dependent on the growth phase and the presence of the protein inducer. Detected enzymes were characterized regarding their substrate specificity, pH tolerance, and susceptibility to inhibitors. In case of the W303a strain, only one type of gelatin-degrading secretory protease (presumably metalloproteinase) was observed. However, the BY4742 strain secreted different proteases of the various catalytic types, depending on the substrate availability. Our study brings the evidence that S. cerevisiae strains secrete several kinds of proteases depending on the presence and type of the substrate. Protein induction may cause not only quantitative but also qualitative changes in the extracellular proteolytic patterns. PMID- 27406380 TI - A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis. AB - Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [(3)H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [(3)H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses. PMID- 27406381 TI - Phyllodes tumors of the breast: Analysis of 35 cases from a single institution. AB - BACKGROUND: Phyllodes tumors are rare fibroepithelial breast tumors with diverse biological behavior. Our study aim is to review the clinico-pathological features, prognostic factors and treatment outcome for patients presenting with phyllodes tumors of the breast to the Kuwait Cancer Control Center (KCCC). PATIENTS AND METHODS: We retrospectively reviewed the clinical and pathological data of 35 women of histologically proved phyllodes tumors of the breast retrieved between January 1994 and December 2012. RESULTS: The median age was 40years (21-63years). The median pathological tumor size was 6.8cm (3-25cm). Histologically, one patient (3%) presented with benign, 13 (37%) with borderline and 21 (60%) with malignant phyllodes. Twenty-eight patients (80%) were premenopausal. Twenty (57%) were ultimately treated with mastectomy (3 borderline, and 17 malignant) and 15 (43%) with conservative surgery (1 benign, 10 borderline and 4 malignant). Axillary staging was carried out in 9 patients (1 borderline and 8 malignant), none of them had nodal metastasis. Four patients with malignant phyllodes received postoperative radiotherapy. After a median follow-up period of 52months (range 5-211months), 5 developed local recurrence (1 benign, 2 borderline and 2 malignant). One patient with malignant phyllodes developed distant lung metastasis. The overall 5-year relapse free survival (RFS) was 74% (68% for borderline and 84% for malignant phyllodes). According to the treatment modality, the 5-year RFS was 69% for conservative surgery compared to 87% for mastectomy. It was 100% for irradiated patients versus 71% for non irradiated patients. CONCLUSION: Phyllodes tumors are rare tumors that occur in relatively young women, when compared with the classical adenocarcinoma of the breast. They have a tendency to reach large sizes with absence of nodal metastasis. Although surgery is the mainstay of management, postoperative radiotherapy also appears to decrease the local recurrence rates in certain presentations. PMID- 27406383 TI - Dilemma-focused intervention for unipolar depression: a treatment manual. AB - BACKGROUND: This article introduces a new treatment protocol for depression. Based on previous research which indicated the presence of cognitive conflicts in depression, this study created an intervention manual to address these conflicts. METHOD: The therapy manual for depressive patients followed the guideline for inclusion in clinical trials (stage II), which has received high recognition. A preliminary version (stage I) of this manual was formulated based on other, more general dilemma-focused therapy publications, inspired by personal construct theory (PCT), and input from clinical experience. The resulting version was then applied during the 8-session format of a pilot study with patients diagnosed with major depressive disorder or dysthymia. Finally, feedback was requested from seasoned and highly respected therapists, some of whom were familiar with PCT. RESULTS: According to the mentioned guideline, the intervention manual selected the theoretical framework, in this case PCT, to include its conceptualization of depression and resolution of dilemmas (to foster clinical improvement) as a main treatment goal. The manual was then contrasted with psychoanalytic psychotherapy, cognitive-behavior therapy (CBT), motivational interviewing (MI), and other similar approaches such as cognitive-analytic therapy and coherence therapy. Following these conceptual clarifications, the specific interventions included in the manual were defined according to both categories: their unique and essential components and those conceived as common psychotherapeutic factors. Next, the general structure and content for each session were presented. The structure consisted of seven well-defined individual sessions with an additional session, which could complement any of the former sessions to address the patient's issues in greater depth, if needed. CONCLUSIONS: This Dilemma-Focused Intervention manual aimed to improve the treatment outcome for depression by offering an intervention that could be combined with other general approaches. At its present level of definition, it allows for inclusion in controlled trials (eg, the current RCT combining group CBT with this intervention). Thus, this manual added to the existing resources in psychotherapeutic research and practice for treatment of depression. PMID- 27406382 TI - Public health and chronic low chlordecone exposure in Guadeloupe, Part 1: hazards, exposure-response functions, and exposures. AB - BACKGROUND: Inhabitants of Guadeloupe are chronically exposed to low dose of chlordecone via local food. The corresponding health impacts have not been quantified. Nevertheless the public authority implemented an exposure reduction program in 2003. We develop methods for quantifying the health impacts of chlordecone and present the results in 2 articles: 1. hazard identification, exposure-response functions (ERF) and exposure in Guadeloupe, 2. Health impacts and benefits of exposure reduction. Here is the first article. METHODS: Relevant data are extracted from publications searched in Medline and Toxline. Available knowledges on mode of action and key-event hazards of chlordecone are used to identify effects of chlordecone that could occur at low dose. Then a linear ERF is derived for each possible effect. From epidemiological data, ERF is the delta relative risk (RR-1) divided by the corresponding delta exposure. From animal studies, ERF is the benchmark response (10 %) divided by the best benchmark dose modeled with BMDS2.4.0. Our goal is to obtain central values for the ERF slopes, applicable to typical human populations, rather than lower or upper bounds in the most sensitive species or sex. RESULTS: We derive ERFs for 3 possible effects at chronic low chlordecone dose: cancers, developmental impairment, and hepatotoxicity. Neurotoxicity in adults is also a possible effect at low dose but we lack quantitative data for the ERF derivation. A renal toxicity ERF is derived for comparison purpose. Two ERFs are based on epidemiological studies: prostate cancer in men aged >44y (0.0019 per MUg/Lblood) and altered neurodevelopment in boys (-0.32 QIpoint per MUg/Lcord-blood). Two are based on animal studies: liver cancer (2.69 per mg/kg/d), and renal dysfunction in women (0.0022 per mg/kg/d). CONCLUSION: The methodological framework developed here yields ERFs for central risk estimates for non-genotoxic effects of chemicals; it is robust with regard to models used. This framework can be used generally to derive ERFs suitable for risk assessment and for cost-benefit analysis of public health decisions. PMID- 27406384 TI - The stimulatory effect of neuropeptide Y on growth hormone expression, food intake, and growth in olive flounder (Paralichthys olivaceus). AB - Neuropeptide Y (NPY) is a 36-amino acid peptide known to be a strong orexigenic (appetite-stimulating) factor in many species. In this study, we investigated the effect of NPY on food intake and growth in the olive flounder (Paralichthys olivaceus). Recombinant full-length NPY was injected intraperitoneally into olive flounder at the dose of 1 MUg/g body weight; phosphate buffered saline was used as the negative control. In a long-term experiment, NPY and control groups were injected every fifth day over a period of 30 days. In a short-term experiment, NPY and control groups were given intraperitoneal injections and maintained for 24 h. Food intake and growth rates were significantly higher in fish injected with recombinant NPY than in the control fish (P < 0.05). Higher growth hormone (GH) and NPY mRNA transcript levels were observed in both experiments, indicating a stimulatory effect of NPY on GH release. These findings demonstrate that NPY is an effective appetite-stimulating factor in olive flounder with the potential to improve the growth of domestic fish species and enhance efficiency in aquaculture. PMID- 27406385 TI - Characterization of a vasa homolog in the brown-marbled grouper (Epinephelus fuscoguttatus) and its expression in gonad and germ cells during larval development. AB - The vasa gene is specifically expressed in the germ cell lineage, and its expression has been used to study germline development in many organisms, including fishes. In this study, we cloned and characterized vasa as Efu-vasa in the brown-marbled grouper (Epinephelus fuscoguttatus). Efu-vasa contained predicted regions that shared consensus motifs with the vasa family in teleosts, including arginine- and glycine-rich repeats, ATPase motifs, and a DEAD box. Phylogenetic-tree construction using various DEAD-box proteins confirmed that Efu vasa was clustered in the vasa family. Efu-vasa mRNA was detectable only in gonads, by reverse transcription polymerase chain reaction. Primordial germ cells (PGCs) during early gonad development in larvae were characterized by histological examination and in situ hybridization using an Efu-vasa antisense probe. Migrating PGCs were found in larvae at 9-21 days post-hatching, and rapid proliferation of PGCs was initiated in 36 days post-hatching. These findings provide a valuable basis for optimizing the developmental stages for germ cell transplantation in order to produce surrogate broodstock, which may help in the production of larvae of large and endangered grouper species. PMID- 27406386 TI - Expression of metalloproteinases (MMP-2 and MMP-9) in basal-cell carcinoma. AB - The aim of this study was to compare the expressions of mRNA for metalloproteinases (MMP-2 and MMP-9) and type IV collagen in two different histological types of basal-cell carcinoma (BCCs; nodular and infiltrative) and in normal tissues from the tumor interface. The study included biopsy specimens of the skin involved with BCC and normal skin adjacent the lesion. The expressions of mRNA for MMP-2, MMP-9 and type IV collagen were determined by means of RT-PCR (Reverse transcription polymerase chain reaction). The level of type IV collagen mRNA in nodular and infiltrative BCCs turned out to be significantly lower, and the expressions of MMP-2 and MMP-9 mRNA significantly higher than in normal tissues adjacent to these tumors. The expression of mRNA for MMP-9 but not for MMP-2 was significantly higher in infiltrative BCCs than in the nodular BCCs. In turn, normal tissues adjacent to nodular BCCs showed significantly higher levels of mRNA for MMP-2 and significantly lower levels of type IV collagen mRNA than the normal tissues from the interface of infiltrative BCCs. The findings suggest that MMP-2 and MMP-9 could be used as prognostic factors of BCCs. PMID- 27406387 TI - Truncated SRA RNA derivatives inhibit estrogen receptor-alpha-mediated transcription. AB - The steroid receptor RNA activator (SRA) is a long non-coding RNA (lncRNA) that acts as a putative coactivator for steroid receptor-mediated transcription. A recent study showed that SRA RNA can be structurally dissected into four domains comprising various secondary structures, but the contribution of each domain to the coactivation ability of SRA RNA was previously unknown. Here, we assessed the functional contributions of the various domains of SRA. We examined the effects of each domain on the coactivation of estrogen receptor-alpha (ERalpha)-mediated transcription of a luciferase reporter gene in HeLa cells. Then the detailed domain analysis was focused on domain III (D3) not only with the reporter gene in HeLa cells, but also with ERalpha-responsive genes in MCF7 breast cancer cells. Domain deletion analysis showed that the deletion of any domain decreased the luciferase activity, and that deletion of D3 caused the largest decrease. This D3 deletion effect was not recovered by co-expression of D3 alone; moreover, the expression of D3 fragments (particularly helices H15-H18, which are highly conserved across vertebrates) inhibited luciferase expression in HeLa cells. Moreover, a fragment containing helices H15-H18 reduced ERalpha-responsive gene expression in MCF7 breast cancer cells. Our findings indicate that D3 inhibited ERalpha-mediated transcription of a reporter gene in HeLa cells and that helices H15-H18, as a core element responsible for the D3-driven inhibition, reduced expression of ERalpha-responsive genes in breast cancer cells. PMID- 27406388 TI - Light touch regulation may be most effective. PMID- 27406389 TI - A fatal yellow fever virus infection in China: description and lessons. AB - Yellow fever (YF) is a viral disease endemic to the tropical regions of Africa and South America. An outbreak of YF has been occurring in Angola, since the beginning of 2016. In March 2016, a 32-year-old Chinese man who returned from Angola was hospitalized and diagnosed with the first case of imported YF in China. Clinical observations, blood viral RNA detection, serological testing and treatments for the patient were performed daily. The virus was isolated in Vero cells, and the complete viral genome was sequenced and analyzed using the next generation genomic sequencing platform. The patient presented with hemorrhagic fever, jaundice and oliguria at day 3 after onset, which rapidly progressed to multisystem organ failure with extremely elevated liver, pancreatic and myocardial enzymes. The patient died despite the intensive supportive treatments that were performed. A liver biopsy showed severe and multilobular necrosis. Viral RNA was detectable throughout the clinical course of the disease. Whole genomic sequence analysis revealed that the virus belongs to the Angola71 genotype. Although the virus has been circulating in Angola for 45 years, only 14 amino-acid substitutions and no amino-acid changes were observed in the membrane and envelope proteins compared with the virus collected in 1971. The presence of this imported YF case in China indicated that with the increase in business travel among countries, YF outbreaks in Africa can lead to the international spread of the disease. The production and use of YF vaccines is, therefore, an urgent issue. PMID- 27406390 TI - Identification of human somatostatin receptor 2 domains involved in internalization and signaling in QGP-1 pancreatic neuroendocrine tumor cell line. AB - Somatostatin exerts inhibitory effects on hormone secretion and cell proliferation via five receptor subtypes (SST1-SST5), whose internalization is regulated by beta-arrestins. The receptor domains involved in these effects have been only partially elucidated. The aim of the study is to characterize the molecular mechanism and determinants responsible for somatostatin receptor 2 internalization and signaling in pancreatic neuroendocrine QGP-1 cell line, focusing on the third intracellular loop and carboxyl terminal domains. We demonstrated that in cells transfected with somatostatin receptor 2 third intracellular loop mutant, no differences in beta-arrestins recruitment and receptor internalization were observed after somatostatin receptor 2 activation in comparison with cells bearing wild-type somatostatin receptor 2. Conversely, the truncated somatostatin receptor 2 failed to recruit beta-arrestins and to internalize after somatostatin receptor 2 agonist (BIM23120) incubation. Moreover, the inhibitory effect of BIM23120 on cell proliferation, cyclin D1 expression, P-ERK1/2 levels, apoptosis and vascular endothelial growth factor secretion was completely lost in cells transfected with either third intracellular loop or carboxyl terminal mutants. In conclusion, we demonstrated that somatostatin receptor 2 internalization requires intact carboxyl terminal while the effects of SS on cell proliferation, angiogenesis and apoptosis mediated by somatostatin receptor 2 need the integrity of both third intracellular loop and carboxyl terminal. PMID- 27406391 TI - Six controversial issues on subclinical Cushing's syndrome. AB - Subclinical Cushing's syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality. The subclinical Cushing's syndrome is not rare, being estimated to be between 0.2-2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing's syndrome screening, diagnosis and treatment. The Altogether to Beat Cushing's syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing's syndrome viewpoint regarding the following controversial issues on Subclinical Cushing's syndrome (SCS): (1) Who has to be screened for subclinical Cushing's syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushing's syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushing's syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushing's syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushing's syndrome surgically or conservatively treated? Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing's syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing's syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing's syndrome. PMID- 27406392 TI - Health system support and health system strengthening: two key facilitators to the implementation of ambulatory tuberculosis treatment in Uzbekistan. AB - Uzbekistan inherited a hospital-based health system from the Soviet Union. We explore the health system-related challenges faced during the scale-up of ambulatory (outpatient) treatment for drug-susceptible and drug-resistant tuberculosis (TB) in Karakalpakstan in Uzbekistan. Semi-structured interviews were conducted with key informants of the TB services, the ministries of health and finance, and their TB control partners. Structural challenges and resource needs were both discussed as obstacles to the expansion of ambulatory TB treatment. Respondents stated need for revising the financing mechanisms of the TB services to incentivize referral to ambulatory TB treatment. An increased workload and need for transportation in ambulatory TB care were also pointed out by respondents, given the quickly rising outpatient numbers but per capita financing of outpatient care. Policy makers showed strong interest in good practice examples for financing ambulatory-based management of TB in comparable contexts and in guidance for revising the financing of the TB services in a way that strengthens ambulatory TB treatment. To facilitate changing the model of care, TB control strategies emphasizing ambulatory care in hospital-oriented health systems should anticipate health system support and strengthening needs, and provide a plan of action to resolve both. Addressing both types of needs may require not only involving TB control and health financing actors, but also increasing knowledge about viable and tested financing mechanisms that incentivize the adoption of new models of care for TB. PMID- 27406393 TI - Plasma kinetics of essential amino acids following their ingestion as free formula or as dietary protein components. AB - This investigation compares the levels of plasma kinetics of plasma essential amino acids (EAAs) after ingestion as free-form EAAs (FEAAs) or EAAs as components of dietary protein (DPEAAs), in eighteen healthy individuals, nine elderly (85 +/- 6.7 years; 4 male) and nine young (28.7 +/- 7 years; 3 males). For two consecutive days, each subject ingested EAAs in the form of (FEAAs) or (DPEAAs) in a random alternate pattern. Five minutes before EAA ingestion (baseline) and 30, 60, 90, 150 and 270 min after, venous blood samples were taken to determine the concentrations of EAAS (micromol/L). In both groups, ingested FEAAs compared to DPEAAs led to faster increase in plasma EAA levels at 30-150 min (p < 0.0001). Moreover, the increased plasma EAAs disappeared faster after FEAA compared to DPEAA. These results may be important in those subjects who have high requirement both for EAAs substrates and anabolic efficiency. PMID- 27406394 TI - Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy: a randomized, open-label, prospective study (VISION). AB - AIMS: To compare the efficacy and safety of combination of vildagliptin and metformin therapy with metformin uptitration in Chinese patients with type 2 diabetes (T2DM) inadequately controlled with low-dose metformin. METHODS: In this 24-week prospective, randomized, multicentre, open-label study, patients with T2DM inadequately controlled with metformin <=1000 mg daily were divided 1 : 1 : 1 : 1 into four prespecified subgroups based on age and body mass index (BMI). Patients in each subgroup were randomized 5 : 1 to receive either vildagliptin (50 mg twice daily) plus metformin [500 mg twice daily; vildagliptin and low-dose metformin (VLDM) group] or metformin uptitration [1000 mg twice daily; high-dose metformin (HDM) group]. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline at week 24. The key secondary endpoints included percentage of patients achieving target HbA1c without adverse gastrointestinal (GI) events and mean change in fasting plasma glucose (FPG) from baseline to week 24. RESULTS: A total of 3084 patients were randomized. HbA1c reduction of 0.54% at week 24 in the VLDM group was non-inferior and statistically superior compared with 0.40% in the HDM group (P < 0.0001). VLDM's non-inferiority to HDM was confirmed in the four subgroups and its superiority was shown for all subgroups (p < 0.05) except for the subgroup of patients aged <60 years with a BMI of >=24 kg/m(2) . Compared with HDM, VLDM significantly increased the percentage of patients achieving HbA1c <=6.5% and HbA1c <=6.5% without GI events. FPG levels in the VLDM group were lower at week 24 numerically than in the HDM group. The two treatment arms had similar safety profiles. CONCLUSIONS: VLDM was non-inferior and statistically superior to HDM in glycaemic control in Chinese patients with T2DM inadequately controlled with low-dose metformin. PMID- 27406395 TI - Liolaemus lizards (Squamata: Liolaemidae) as hosts for the nymph of Amblyomma parvitarsum (Acari: Ixodidae), with notes on Rickettsia infection. AB - Adults of Amblyomma parvitarsum are common ectoparasites of South American camelids of the genera Lama and Vicugna, occuring in highlands of Argentina, Bolivia, Chile, Peru and also in Argentinean Patagonia. Whereas larval stages of this tick are known to feed on small lizards, host records for the nymphal instar have remained unreported. Supported by morphological and molecular analyses, herein we report A. parvitarsum nymphs parasitizing two Liolaemus species (Reptilia: Squamata) in the Andean Plateau of Argentina and Chile. Additionally, by a PCR screening targetting gltA and ompA genes, DNA of Rickettsia was detected in one of the collected nymphs. Obtained sequences of this agent were identical to a recent Rickettsia sp. described infecting adults of this tick species in Chile and Argentina. PMID- 27406396 TI - Therapeutic algorithm to treat common iliac artery aneurysms by endovascular means. AB - Use of endovascular means is gaining ever greater acceptance in the treatment of aorto-iliac aneurysms. Especially, the treatment of patients with common iliac aneurysms (CIAs) may be very challenging due to the complexity of the underlying disease with often involvement of the hypogastric artery. Additionally, the variety of endovascular therapeutic options such as the use of iliac branch devices, parallel grafts, the bell-bottom technique or coil embolization of the hypogastric artery and overstenting of the origin represents significant limitation regarding the presentation of a clear and robust endovascular therapeutic algorithm. Aim of the present article was the demonstration of the institutional experience with the endovascular management of CIAs in order to provide a clinical recommendation and algorithm. PMID- 27406398 TI - One step forward, five steps back? The re-emergence of Victorian diseases in the UK. PMID- 27406397 TI - The effects of music on the cardiac resuscitation education of nursing students. AB - PURPOSE: The purpose of this study is to examine the effects of music on the appropriate performance of the rate and depth of chest compression for nursing students. METHODS: This randomized controlled study was conducted in the School of Nursing in Turkey between November 2014 and January 2015. The study's participants were second-year nursing school students with no previous formal cardiac resuscitation training (n=77). Participants were randomly assigned to one of two groups: an intervention group with music and a control group without music. During practical training, the intervention group performed chest compressions with music. The outcomes of this study were collected twice. The first evaluation was conducted one day after CPR education, and the second evaluation was conducted six weeks after the initial training. RESULTS: The first evaluation shows that the participants in the intervention group had an average rate of 107.33+/-7.29 chest compressions per minute, whereas the rate for the control group was 121.47+/-12.91. The second evaluation shows that the rates of chest compression for the intervention and control groups were 106.24+/-8.72 and 100.71+/-9.54, respectively. CONCLUSION: The results of this study show that a musical piece enables students to remember the ideal rhythm for chest compression. Performing chest compression with music can easily be integrated into CPR education because it does not require additional technology and is cheap. PMID- 27406399 TI - Food insecurity and diabetes self-management among food pantry clients. AB - OBJECTIVE: To examine the association between level of food security and diabetes self-management among food pantry clients, which is largely not possible using clinic-based sampling methods. DESIGN: Cross-sectional descriptive study. SETTING: Community-based food pantries in California, Ohio and Texas, USA, from March 2012 through March 2014. SUBJECTS: Convenience sample of adults with diabetes queuing at pantries (n 1237; 83 % response). Sampled adults were stratified as food secure, low food secure or very low food secure. We used point of-care glycated Hb (HbA1c) testing to determine glycaemic control and captured diabetes self-management using validated survey items. RESULTS: The sample was 70 % female, 55 % Latino/Hispanic, 25 % white and 10 % black/African American, with a mean age of 56 years. Eighty-four per cent were food insecure, one-half of whom had very low food security. Mean HbA1c was 8.1 % and did not vary significantly by food security status. In adjusted models, very-low-food-secure participants, compared with both low-food-secure and food-secure participants, had poorer diabetes self-efficacy, greater diabetes distress, greater medication non adherence, higher prevalence of severe hypoglycaemic episodes, higher prevalence of depressive symptoms, more medication affordability challenges, and more food and medicine or health supply trade-offs. CONCLUSIONS: Few studies of the health impact of food security have been able to examine very low food security. In a food pantry sample with high rates of food insecurity, we found that diabetes self-management becomes increasingly difficult as food security worsens. The efficacy of interventions to improve diabetes self-management may increase if food security is simultaneously addressed. PMID- 27406400 TI - Sea otters, social justice, and ecosystem-service perceptions in Clayoquot Sound, Canada. AB - We sought to take a first step toward better integration of social concerns into empirical ecosystem service (ES) work. We did this by adapting cognitive anthropological techniques to study the Clayoquot Sound social-ecological system on the Pacific coast of Canada's Vancouver Island. We used freelisting and ranking exercises to elicit how locals perceive ESs and to determine locals' preferred food species. We analyzed these data with the freelist-analysis software package ANTHROPAC. We considered the results in light of an ongoing trophic cascade caused by the government reintroduction of sea otters (Enhydra lutris) and their spread along the island's Pacific coast. We interviewed 67 local residents (n = 29 females, n = 38 males; n = 26 self-identified First Nation individuals, and n = 41 non-First Nation individuals) and 4 government managers responsible for conservation policy in the region. We found that the mental categories participants-including trained ecologists-used to think about ESs, did not match the standard academic ES typology. With reference to the latest ecological model projections for the region, we found that First Nations individuals and women were most likely to perceive the most immediate ES losses from the trophic cascade, with the most certainty. The inverse was found for men and non-First Nations individuals, generally. This suggests that 2 historically disadvantaged groups (i.e., First Nations and women) are poised to experience the immediate impacts of the government-initiated trophic cascade as yet another social injustice in a long line of perceived inequities. Left unaddressed, this could complicate efforts at multistakeholder ecosystem management in the region. PMID- 27406401 TI - How to control optical activity in organic-silver hybrid nanoparticles. AB - The mechanisms that originate and control optical activity in organic-metal hybrid nanoparticles (NPs) are identified using a time-perturbed density functional theory. Electronic circular dichroism (CD) is studied in terms of the intrinsic chirality of the ligands, the number of ligands and the induced chirality by the arrangement of the ligands on the NP. Left-handed cysteine and achiral methylthio ligands adsorbed on an icosahedral silver NP are investigated. The analysis of CD allows the identification of the spectral regions when the induced chirality by the ligand array dominates over the intrinsic chirality of the ligands, determining conditions for CD control and enlargement. These results would be significant in the discussion of experimental CD spectra of organic metal hybrid NPs, which might allow the development of new strategies to improve the sensitivity of chiroptical spectroscopies for the identification of bio and organic molecules. PMID- 27406402 TI - Evolutionary and environmental determinants of freshwater fish thermal tolerance and plasticity. AB - Understanding the extent to which phylogenetic constraints and adaptive evolutionary forces help define the physiological sensitivity of species is critical for anticipating climate-related impacts in aquatic environments. Yet, whether upper thermal tolerance and plasticity are shaped by common evolutionary and environmental mechanisms remains to be tested. Based on a systematic literature review, we investigated this question in 82 freshwater fish species (27 families) representing 829 experiments for which data existed on upper thermal limits and it was possible to estimate plasticity using upper thermal tolerance reaction norms. Our findings indicated that there are strong phylogenetic signals in both thermal tolerances and acclimation capacity, although it is weaker in the latter. We found that upper thermal tolerances are correlated with the temperatures experienced by species across their range, likely because of spatially autocorrelated processes in which closely related species share similar selection pressures and limited dispersal from ancestral environments. No association with species thermal habitat was found for acclimation capacity. Instead, species with the lowest physiological plasticity also displayed the highest thermal tolerances, reflecting to some extent an evolutionary trade-off between these two traits. Although our study demonstrates that macroecological climatic niche features measured from species distributions are likely to provide a good approximation of freshwater fish sensitivity to climate change, disentangling the mechanisms underlying both acute and chronic heat tolerances may help to refine predictions regarding climate change-related range shifts and extinctions. PMID- 27406403 TI - The active sites of supported silver particle catalysts in formaldehyde oxidation. AB - Surface silver atoms with upshifted d-orbitals are identified as the catalytically active sites in formaldehyde oxidation by correlating their activity with the number of surface silver atoms, and the degree of the d-orbital upshift governs the catalytic performance of the active sites. PMID- 27406404 TI - Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL. AB - Cervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (>=0.2 MUm). We compare these results with analyses following attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 MUm to 30 MUm due to the optical diffraction limit. PMID- 27406405 TI - Identification of an NDM-5-producing Escherichia coli Sequence Type 167 in a Neonatal Patient in China. AB - Emergence of New Delhi metallo-beta-lactamase-producing Enterobacteriaceae has become a challenging threat to public health. Two carbapenem-resistant Escherichia coli, strain QD28 and QD29, were recovered from the aspirating sputum of a neonate and the urine of an adult in a Chinese hospital in 2013. Molecular typing revealed that both isolates belonged to the sequence type 167, but they were clonally diverse. Both isolates exhibited resistance to carbapenems, cephalosporins, ciprofloxacin, gentamicin, piperacillin-tazobactam and trimethoprim-sulfamethoxazole. In addition, strain QD28 was also resistant to aztreonam, and strain QD29 was resistant to amikacin, fosfomycin and minocycline. Antimicrobial resistance gene screening revealed that strain QD28 harbored aac(6')-Ib, blaCTX-M-14, blaNDM-5, blaTEM-1 and sul1 genes, and strain QD29 harbored aac(6')-Ib, blaCTX-M-3, blaNDM-5, blaTEM-1, rmtB, sul1 and sul2 genes. The blaNDM-5 gene was found to be located on a 46-kb plasmid in two isolates, and further sequence analysis showed that this plasmid was highly similar to the previously reported IncX3 plasmid pNDM-MGR194 in India. This is the first identification of blaNDM-5-carrying E. coli in the neonatal infection. PMID- 27406407 TI - The unique Raman fingerprint of boron nitride substitution patterns in graphene. AB - Boron nitride-substituted graphene (BNsG) two-dimensional structures are new materials of wide technological interest due to the rich variety of electronic structures and properties they can exploit. The ability to accurately characterize them is key to their future success. Here we show, by means of ab initio simulations, that the vibrational Raman spectra of such compounds are extremely sensitive to substitution motifs and concentration, and that each structure has unique and distinct features. This result can be useful as a guide for the optimization of production processes. PMID- 27406406 TI - Resting-state functional connectivity differentiates anxious apprehension and anxious arousal. AB - Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations. PMID- 27406408 TI - Recent Advances in the Synthesis of Heterocycles and Related Substances Based on alpha-Imino Rhodium Carbene Complexes Derived from N-Sulfonyl-1,2,3-triazoles. AB - In recent years, alpha-imino rhodium carbene complexes derived by ring-opening of N-sulfonyl-1,2,3-triazoles have attracted much attention from organic chemists. Many transformations of these species have been reported that involve, in most cases, nucleophilic attack at the carbene center of the alpha-imino rhodium carbene, facilitating the synthesis of a wide range of novel and useful compounds, particularly heterocycles. This Minireview mainly focuses on advances in the transformation of N-sulfonyl-1,2,3-triazoles during the past two years. PMID- 27406410 TI - Lipid and lipoprotein oxidation: basic mechanisms and unresolved questions in vivo. PMID- 27406409 TI - Toxicity Testing of Silver Nanoparticles in Artificial and Natural Sediments Using the Benthic Organism Lumbriculus variegatus. AB - The increased use of silver nanoparticles (AgNP) in industrial and consumer products worldwide has resulted in their release to aquatic environments. Previous studies have mainly focused on the effects of AgNP on pelagic species, whereas few studies have assessed the risks to benthic invertebrates despite the fact that the sediments act as a large potential sink for NPs. In this study, the toxicity of sediment-associated AgNP was evaluated using the standard sediment toxicity test for chemicals provided by the Organization of Economic Cooperation and Development. The freshwater benthic oligochaete worm Lumbriculus variegatus was exposed to sediment-associated AgNP in artificial and natural sediments at concentrations ranging from 91 to 1098 mg Ag/kg sediment dry weight. Silver nitrate (AgNO3) was used as a reference compound for Ag toxicity. The measured end points of toxicity were mortality, reproduction, and total biomass. In addition, the impact of sediment-associated AgNP on the feeding rate of L. variegatus was studied in a similar test set-up as mentioned previously. The addition of AgNP into the sediment significantly affected the feeding rate and reproduction of the test species only at the highest concentration (1098 mg/kg) of Ag in the natural sediment with the lowest pH. In comparison, the addition of AgNO3 resulted in reproductive toxicity in every tested sediment, and Ag was more toxic when spiked as AgNO3 than AgNP. In general, sediments were observed to have a high capacity to eliminate the AgNP-derived toxicity. However, the capacity of sediments to eliminate the toxicity of Ag follows a different pattern when spiked as AgNP than AgNO3. The results of this study emphasize the importance of sediment-toxicity testing and the role of sediment properties when evaluating the environmental effects and behavior of AgNP in sediments. PMID- 27406411 TI - Amplified nitric oxide production by pulmonary alveolar macrophages of newborn rats. AB - Oxygen (O2)-dependent and O2-independent antimicrobial mechanisms are used by alveolar macrophages (AM) to maintain lung sterility, but these mechanisms are underdeveloped in neonatal AM. Nitric oxide (NO(.)), a more recently described antimicrobial and immunomodulating molecule, has not been studied in neonatal AM. Lavaged AM from 3-day-old, 10-day-old, maternal and adult rats were treated with or without lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma) and NO(.) synthase activity was measured as its L-arginine metabolites: NO2(-), NO3(-), and citrulline. Superoxide anion (O2(.-)) production by suspended macrophages, initiated by either opsonized zymosan or phorbol, was used as a marker of O2 dependent antimicrobial activity. Lysozyme content of AM was measured as a component of O2-independent antimicrobial activity. Unstimulated 3-day-old macrophages generated >10-fold more NO2(-) + NO3(-) than did 10-day-old, maternal or adult AM. Twenty hours after LPS and IFN-gamma stimulation, 3-day-old AM produced > 2 times more NO2(-) and NO3(-) than did the more mature macrophages. Basal and stimulated O2(.-) release was similar among 3-day-old, 10-day-old and adult AM, while lysozyme concentrations were > 4-fold higher in adult macrophages compared to AM from 3-day-old pups. Rather than having a role in NO(.)-dependent antimicrobial activity, we propose that newborn AM have amplified NO(.) production to modulate their own differentiation and replication after birth. The age-dependent differences in NO(.) synthase expression by AM may lend insight into the regulation of this important enzyme. PMID- 27406412 TI - Respective roles of nitric oxide and superoxide radical in the respiratory burst activity of rat polymorphonuclear leukocytes induced by hyperthyroidism. AB - Administration of single doses of 0.1 mg of L-3,3',5-triiodothyronine (T3)/kg for 3 consecutive day to fed rats elicited a marked increase both in the opsonized zymosan-induced luminal-amplified integrated chemiluminescence (ICL) of isolated polymorphonuclear leukocytes (PMN) in the absence (200%) and presence (228%) of L arginine, and in the rate of superoxide radical (O2(.-)) production (180%). In the presence of L-arginine, the ICL was significantly increased by 57 and 17% over values observed in its absence, in PMN from control rats and T3-treated animals, respectively, an effect that was completely abolished by Nomega-nitro-L arginine. However, the net L-arginine-dependent ICL was comparable in stimulated PMN from both experimental groups, and the respective rates of nitric oxide (NO(.)) production were not significantly different, either in the absence or presence of nitro-L-arginine methyl ester. It is concluded that thyroid hormone induced respiratory burst activity of rat PMN is not dependent on changes in NO(.) synthase activity, but rather on the adaptive increase in O2(.-) generation by NADPH oxidase. PMID- 27406413 TI - Selenium supplementation decreases the pro-oxidant and cardiotoxicity effects of adriamycin in the rat. AB - Adriamycin (doxorubicin; ADR) is an antineoplastic drug used to treat various cancers; however, its chronic us is unfortunately accompanied by cardiotoxicity. Previous results suggested that a free radical mechanism may contribute to ADR toxicity. Because it is often reported that cancer patients are deficient in selenium (Se), we hypothesised that ADR toxicity might be reduced by antioxidant agents such as vitamin E and Se. ADR-induced cardiotoxicity was examined in rats maintained on a Se-supplemented diet. The animals were kept on either a standard (0.22 mg/kg) or a Se-supplemented (2.5 mg/kg) diet starting 4 weeks prior to the first ADR treatment. ADR, or its excipient, was administered intraperitoneally in six equal injections over a period of 3 weeks giving a cumulative dose of 15 mg/kg body weight. Blood was collected in the thoracic cavity and the heart was subjected to a sequence of perfusion/partial ischemia/reperfusion ex vivo. Se status, GPx activities, vitamins E and C and MDA contents were determined on RBC and cardiac homogenates. ADR-treated rats showed a significant decrease in RBC Se (-29%) and in RBC Se-GPx (-34%) compared to the placebo group, and a significant increase in RBC MDA content (+2000%). This latter increase was attenuated by the Se supplementation (+1600%). In parallel, RBC vitamin E decreased markedly in the ADR-treated group (-50%) and was totally restored by the Se supplementation. Cardiac biochemical analyses confirmed the blood results. The present data confirm that a free radical mechanism does contribute to ADR toxicity, and show the importance of balancing the Se levels in ADR-treated subjects to limit its harmful myocardial action. Adecrease in ADR toxicity with no concomitant decrease in its antineoplastic activity would be of considerable value by improving the therapeutic benefit of the drug. PMID- 27406414 TI - Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. AB - The antioxidant activity of an anti-ischemic agent, 3-methyl-1-phenyl-2-pyrazolin 5-one (MCI-186), was examined. The pKa value of MCI-186 is 7.0 and the rate of oxidation of MCI-186 initiated with an azo compound increased with increasing pH, suggesting that the anionic form of MCI-186 is much more reactive than the non ionic form. The major products were 3-methyl-1-phenyl-2-pyrazolin-4,5-dione (4,5 dione) and 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB). Hydrolysis of 4,5-dione gave OPB. The minor intermediate product was 4-hydroxy-4-(3-methyl-1-phenyl-1H pyrazolin-5-on-4-yl)-3-methyl-1-phenyl-1H-pyrazolin-5-one (BPOH). The nucleophilic attack of the anionic form of MCI-186 to 4,5-dione is likely to give BPOH. MCI-186 (50 MUM) inhibited the aerobic oxidation at 37 degrees C of 5.2 mM unilamellar soybean phosphatidylcholine (PC) liposomal membranes, initiated with a water-soluble initiator, as efficientlyas did ascorbate (100 MUM). MCI-186 (50 MUM) also inhibited the oxidation of the same PC liposomal membranes, this time initiated with a lipid-soluble initiator, almost as efficiently as did alpha tocopherol (2 MUM). Furthermore, the combination of MCI-186 with ascorbate or alpha-tocopherol showed almost complete inhibition of PC oxidation induced by both initiators. These data suggest that MCI-186 may work as a good antioxidant in cellular systems as well as in cell-free systems. PMID- 27406415 TI - Role of the prosthetic groups of NADPH-cytochrome P450 reductase in 3 hydroxyanthranilamide-catalyzed, NADPH-dependent superoxide anion production. AB - The role of the prosthetic groups (FAD and FMN) of NADPH-cytochrome P450 reductase (P450 reductase)in 3-hydroxyanthranilamide (3-OH An.Amide)-catalyzed, NADPH-dependent superoxide anion (O2-) production via the reductase was examined using the native and FMN-depleted preparations of P450 reductase which was partially purified from rat liver microsomes. NADPH-dependent O2-production by the FMN-depleted preparation was about 10% of that by the native preparation. 3 OH An. Amide-catalyzed, NADPH-dependent O2-production by the FMN-depleted preparation was less than 10% of that by the native preparation. FMN supplementation returned O2-production to near normal. We observed the same results for NADPH oxidation and hydrogen peroxide formation. O2-production, NADPH oxidation, and hydrogen peroxide formation were inhibited by native superoxide dismutase (SOD), but not by boiled, denatured SOD. These results indicate that the prosthetic groups, especially FMN, of P450 reductase play a critical role in 3-OH An.Amide-catalyzed, NADPH-dependent O2-production via the reductase. PMID- 27406417 TI - Reaction of peroxynitrite with L-tryptophan. PMID- 27406416 TI - Inhibitory effect of phenyl N-terf-butyl nitrone on Kupffer cell phagocytosis. AB - Light microscopy studies of rat liver were conducted after injection of India ink. The data indicated that Kupffer cell phagocytosis was inhibited by C-phenyi N-tert-butyl nitrone (PBN), as well as by the Kupffer cell antagonist gadolinium chloride. PMID- 27406420 TI - Phenolic recovery and bioaccessibility from milled and finished whole grain oat products. AB - While much is known about the benefits of oat fiber, the relevance of phenolics from oat based food products remains unclear. To gain insight into the relevance of phenolics from consumer oat products, the content of phenolics and avenanthramides (AVEs) was followed in 10 oat cultivars as well as milled oat ingredients and ready to eat (RTE) consumer products (puffed cereals and snack bars). Free phenolic content ranged from 17.2 to 228.1 MUg g(-1) DW with AVEs accounting for 57.3-90.6% of the total free phenolics. Bound phenolic content ranged from 141.4 to 680.9 MUg g(-1) DW with ferulic acid accounting for 62-94% of the bound phenolics. Select oat groats were ground to flour and prepared as wet cooked porridges (~20% oat flour in boiling water) or introduced as RTE products into a three stage in vitro digestion to determine phenolic bioaccessibility. The relative bioaccessibility for wet cooked porridges ranged from 0.3-2.6% and from 2.9-28.8% for individual phenolic acids and AVEs, respectively. Puffed oat cereal had significantly higher bioaccessibility compared to matching wet-cook porridge made from the same oat flour (e.g. 83.8% versus 19.1% for AVE A; p < 0.05). Intestinal uptake of bioaccessible oat phenolics from digesta was confirmed by experiments with Caco-2 human intestinal cells. The overall intestinal uptake of oat phenolics was low, ranging between 0.16% and 2.71% across digesta from all oat products. In conclusion, these experiments demonstrate that phenolics naturally present in whole grain oats are recovered well through traditional grain processing, milling and food processing. Furthermore, processing of oat cultivars into a RTE cereal may have a positive impact on the digestive release and bioaccessibility of oat phenolics in the upper GI tract. PMID- 27406421 TI - Two SNPs Associated With Spontaneous Dizygotic Twinning: Effect Sizes and How We Communicate Them. AB - In a recent GWAS of spontaneous dizygotic twinning, Mbarek et al. (The American Journal of Human Genetics, 2016, Vol 98, pp. 898-908) identified two SNPs, rs11031006 (near FSHB) and rs17293443 (in SMAD3). In the present note, we address the question how to present the results in terms of effect sizes in a manner that is comprehensible to the general audience (e.g., mothers of twins, readership of newspapers). We propose to avoid the standard effect sizes such as odds ratios and relative risk as these require some knowledge of probability theory. Rather, we convey the results in terms of the conditional probabilities, but expressed in natural language. PMID- 27406422 TI - Outcomes of General Anesthesia and Conscious Sedation in Endovascular Treatment for Stroke. AB - Background Recent studies have strongly indicated the benefits of endovascular therapy for acute ischemic stroke, but what remains a continued debate is the role for general anaesthesia versus conscious sedation (CS) for such procedures. Retrospective studies have found poorer neurological outcomes in patients who underwent general anesthesia (GA); however, some have revealed worse baseline stroke severity in these patients. Methods This study is a retrospective cohort study aimed at comparing mortality and morbidity of GA versus CS in patients treated with endovascular intervention in acute ischemic stroke. Chi-square and t test analyses were used. Results Patients in the GA (n=42) group were more likely to be deceased than those in the CS (n=67) group at hospital discharge, 3 months, and 6 months poststroke onset. Morbidity, as defined by modified Rankin Score, was significantly greater in the GA group at hospital discharge, and a similar trend was seen in morbidity at 3 months postdischarge. Conclusion General anesthesia for endovascular intervention in acute ischemic stroke was associated with increased mortality and poorer neurological incomes compared with conscious sedation. In our study, age, gender, history of hypertension, history of diabetes, and baseline National Institute of Health Stroke Scale were not significantly different between the groups. Although the need for a randomized, prospective study on this topic is clear, our study represents further corroboration of the safety and efficacy of conscious sedation in these procedures. PMID- 27406423 TI - Intensified Induction and Post-Remission Therapy for Acute Myeloid Leukaemia. AB - Standard induction therapy of acute myeloid leukemia (AML) with standard dose chemotherapy will result in 52-72% of patients achieving a complete remission (CR) and only 20% long term survivors. Newer agents which intensify induction therapy appear to improve the outcome of induction include etoposide, idarubicin and high dose cytarabine. New studies are now required to define new induction combinations and the place of these and other promising new drugs in the treatment. Standard attenuated post-remission therapy is required after standard induction to maintain remission. However, new intensified post-remission therapies have significantly improved outcome in de novo patients. This development has required re-examination of the value of intensive treatment. There is now clear clinical evidence that a dose-response effect is present for cytarabine in AML. The optimal placement of intensified treatment and marrow transplantation requires further study. PMID- 27406424 TI - Optimising Treatment for Elderly Patients with Acute Leukaemia. PMID- 27406425 TI - Why Collaboration is Necessary Between Worldwide Bone Marrow Registries. PMID- 27406426 TI - Haematologic Malignancy Secondary to the Treatment of Lymphoma. AB - Modern-day treatment for the malignant lymphomas has resulted in an improved remission rate and survival. However, in the longer run, many of these regimens are associated with a significant incidence of secondary haematologic malignancies. This study further defines this occurrence. The records from 2196 consecutive patients with lymphoreticular neoplasms were retrospectively reviewed. In each case management was on a standard chemotherapy or irradiation protocol, approved by institutional review committees, and based on histopathology coupled with clinical stage at presentation. Diagnosis of myelodysplasia or acute leukaemia was made according to the French-American British (FAB) criteria. From 1970 to 1990, 475 individuals with Hodgkin's Disease, and a further 1721 with other malignant lymphomas, were treated. Myelodysplasia developed in 4, acute myeloblastic leukaemia in 6, possible acute lymphoblastic leukaemia in 1 and, in the remaining case, precise characterization was not possible. Of these twelve patients, comprising 0.5% of the study cohort, 5 (1.1%) had Hodgkin's Disease and seven (0.4%) other lymphoreticular tumours. The median age was sixty-eight (range 33 to 81) years; seven were male. The median latent period from therapy to onset of the secondary neoplasms was 5.6 years (range 1-15.6). Treatment was possible in four of the twelve: two achieved complete remission but relapsed, two had only partial response. None survived fourteen months. Although the incidence is small, it is again noteworthy that all but one of the patients had received alkylating agents and this re-emphasizes the need to develop effective regimens with Jess carcinogenic potential. PMID- 27406427 TI - Antiphospholipid Antibodies and Associated Clinical Manifestations. AB - The Antiphospholipid Syndrome (APS) is defined by the association between antiphospholipid antibodies, i.e. anticardiolipin (aCL) and/or lupus anticoagulant (LA) antibodies, and one or more of the following clinical manifestations: arterial and venous thrombosis, recurrent abortions and thrombocytopenia (1). Among them, deep venous thromboses, pulmonary embolism and thrombosis of the cerebral arteries are the most frequent events, occurring in approximately 1/3 of the patients. Thrombosis of the placental vessels (2) is considered the cause of the obstetrical complications (recurrent spontaneous abortions, fetal deaths or fetal growth retardation) suffered by approximately 10% of the women with antiphospholipid antibodies (1), whereas a variable degree of thrombocytopenia is reported by about 20-25% of the patients (3). Less commonly, skin necrosis, livedo reticularis, hemolytic anemia, dementia or other neuropsychiatric events and the so-called "catastrophic" APS may also develop in the setting of APS (4, 5). Two types of APS have been described: the "Primary" APS, which occurs in the absence of an underlying disease (6), and the "Secondary" APS, which is related to Systemic Lupus Erythematosus (SLE), other autoimmune or neoplastic diseases or other pathological conditions (7). Noteworthy, a substantial amount of patients suffering from APS are young: 50% of the patients enrolled in the Italian Registry of Antiphospholipid Antibodies were aged less than 40 years (8). PMID- 27406428 TI - The Effect of Hemodialysis on the Expression of Platelet Glycoproteins Ib, IIb/IIIa and P-Selectin. AB - To determine the effect of hemodialysis on expression of platelet receptors in patients with chronic renal failure. DESIGN: Blood sampling performed in chronic HD patients prior to the dialysis session, then 15 and 180 minutes into HD. Both dialysis machine inlet and outlet samples were taken at 15 minutes. Control subjects had a single blood sample taken. PATIENTS: Thirteen adult males on chronic hemodialysis and 20 age and sex matched healthy controls. MEASUREMENTS: Flow-cytometric analysis of platelet GP-Ib, GP-IIb/IIIa, and P-selectin. Plasma vWF multimers were analyzed by SDS-polyacrylamide gel electrophoresis and immunoblotting. RESULTS: Mean channel fluorescence (MCF) for GP lb was significantly (P < 0.05) decreased in pre-dialysis patients compared to controls and decreased further 3 hours into the dialysis session compared to the start of the dialysis treatment (P < 0.01). MCF for GP IIb/IIIa between predialysis patients and controls was similar, but decreased after a single dialysis session (P < 0.01). MCF for P-selectin on platelets was similar in patients and controls, but fewer platelets from the patients expressed P-selectin compared to controls (P < 0.05). Qualitative multimeric analysis of the vWF in patients, pre- and post HD was unchanged. CONCLUSIONS: Alterations in platelet surface expression of GPIb, GPIIb/IIIa, and P-selectin may, partially contribute to the changes in platelet function seen in patients on hemodialysis. It is unlikely that alterations in the surface expression of these receptors alone can adequately account for the complex platelet and hemostatic changes associated with uremia and the HD procedure. PMID- 27406429 TI - Soluble Receptors for Tumor Necrosis Factor and Neopterin as Parameters of Cell Mediated Immune Activation. AB - Tumor necrosis factor-alpha is a pleiotropic cytokine which is capable of inducing numerous immunological and biochemical changes in target cells and tissues, Soluble tumor necrosis factor-alpha receptors function to modulate the biological properties of tumor necrosis factor-alpha by enhancing or counteracting its action. In various pathologic states the production and release of soluble tumor necrosis factor receptors may mediate host response and determine the course and outcome of disease by the interaction with tumor necrosis factor-alpha and competing with cell surface receptors. The actual and forthcoming research of soluble tumor necrosis factor receptors in body fluids such as plasma or serum is a new tool to gain information about immune processes and is providing valuable insight into a variety of pathological conditions. In various diseases concentrations of sTNF-Rs correlate strongly with levels of neopterin, large amounts of which being released from human monocytes/macrophages upon stimulation with interferon-gamma. Like neopterin, sTNF-Rs levels show high accuracy in the follow-up and prognosis of various diseases and correlate with the clinical stage and the progression of human immunodeficiency virus infection and sepsis. In cancer and autoimmune diseases, measurement of sTNF-Rs and neopterin provides useful information for monitoring. The quantification of sTNF Rs and neopterin concentrations often provide even superior information than that obtained with classical disease markers, probably due to the direct involvement of the "interferon-gamma/tumor necrosis factor-alpha system" in the pathogenetic mechanisms of the diseases. Data imply that measurement of sTNF-Rs, especially of the 75kD-type, is a useful adjunct for quantification of the Th-1 type immune response, sharing many characteristics with neopterin. PMID- 27406430 TI - Granulocyte-Colony Stimulating Factor (G-CSF) Administration for Chemotherapy Induced Neutropenia. AB - This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm(3) for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia. PMID- 27406431 TI - Parenteral Iron and Recombinant Human Erythropoietin Therapy to Stimulate Erythropoiesis in Patients Undergoing Repair of Hip Fracture. AB - We have previously demonstrated the value of erythropoietin therapy and oral iron supplementation coupled with autologous blood donation in patients undergoing elective orthopaedic procedures. For patients undergoing non-elective surgery such as repair of hip fracture, however, alternative approaches to blood conservation must be developed. To investigate one approach, patients undergoing surgical repair of hip fracture were administered parenteral iron (Iron Dextran USP, 100 mg daily by continuous intravenous infusion) and recombinant human erythropoietin (EPO, 150 u/kg subcutaneously daily) during hospitalization in order to stimulate erythropoiesis. Of nine evaluable patients, three showed evidence of low iron stores. The median total iron therapy administered was 500 mg (the equivalent of 2 1/2 blood units). The median total EPO dose administered was 737 u/kg. The median estimated red blood cell volume produced by the combined therapy was 398 ml (the equivalent of two blood units). Six of eight patients who had reticulocyte data available showed increases in reticulocyte counts. The median admission and discharge hematocrit levels were 35.2% and 31.8%, respectively. Six of nine patients did not require allogeneic blood units. We conclude that parenteral iron supplementation and EPO therapy can stimulate effective erythropoiesis in hip fracture patients, and provide a possible approach to blood conservation in these non-elective surgical patients. PMID- 27406432 TI - Indications for and Value of Bone Marrow Trephine Biopsy in Haematological Disorders. AB - The bone marrow in haematological disorders has traditionally been investigated in small samples of marrow obtained by aspiration Although the value of solid tissue preparations in the diagnosis of bone marrow disorders has long been recognised (1,2), it is only recently that the technique has gainec acceptance among haematologist and oncologists (3). This is specifically due to the development of new needles (4,5) that ensure an effective, atraumatic procedure and also impose little or no damage upon the biopsied tissue. Further, the technique of processing bone marrow trephine biopsies (BMTB) in plastic (methyl- and glycol-methacrylate) (6,7) eliminates the requirement for decalcification (and its attendant abuse of the specimen) while providing thin 1-2 MUm sections (as opposed to the standard 5-8 MUm paraffin sections) that are stainable with Romanowsky stains (eg. Giemsa, May-Grunwald & Giemsa)instead of the routinely utilised, less specific H & E stain. The introduction of enzyme and immunohistological techniques on plastic(glycolmethacrylate) embedded bone marrow biopsies has improved the diagnostic evaluation of bone marrow (7,8,9). The ability to perform molecular studies on BMTB specimens has now added a new dimension in the diagnostic evaluation of bone marrow in haematological disorders such as the leukaemias, myelodysplastic syndromes and malignant lymphomas with bone marrow infiltration (10,11). PMID- 27406433 TI - Technetium-99m Sestamibi Scanning Reflects Marrow Activity in a beta-Thalassemia Patient Treated with an Allogeneic Bone Marrow Transplant. AB - beta-thalassemia major is a disorder of globin synthesis, resulting in anemia and compensatory bone marrow hyperproliferation. Conventional imaging studies do not measure bone marrow activity reliably. We report on the use of technetium-99m sestamibi (MIBI) in a beta-thalassemia major patient treated with an allogeneic bone marrow transplant. Pre-transplant and early post-transplant MIBI scannings demonstrated generalized marrow uptake, reflecting marrow hyperproliferation. After full engraftment, post-transplant MIBI showed disappearance of abnormal uptake in the skeleton, indicating normalization of the marrow activity. MIBI scan may be used as a noninvasive measure of bone marrow proliferation that may guide hypertransfusion therapy in thalassemia patients. PMID- 27406435 TI - Scalp psoriasis and biologic agents: a retrospective, comparative study from a tertiary psoriasis referral centre. AB - BACKGROUND: The scalp is a frequent and difficult-to-treat localization of psoriasis. Little evidence exists regarding the use of biologic agents in recalcitrant cases of scalp psoriasis that are resistant to other treatment options. OBJECTIVES: To evaluate and compare the efficacy of currently available biologic agents (infliximab, etanercept, adalimumab, ustekinumab) in the treatment of scalp symptoms in patients suffering from moderate to severe plaque psoriasis. MATERIALS AND METHODS: This retrospective cohort study consisted of a review of the database of all psoriasis patients who suffered from scalp symptoms and received biologic treatment between January 2012 and December 2014. The patients were divided into four groups based on the drug administered. Scalp psoriasis severity was assessed by the Psoriasis Scalp Severity Index (PSSI) at baseline and at weeks 4, 12, 24 and 48. Psoriasis severity was evaluated with the Psoriasis Area and Severity Index (PASI) at the same time points. RESULTS: In total, 145 patients were enroled in the study (infliximab n = 35, etanercept n = 30, adalimumab n = 39, ustekinumab n = 41). At week 4, the infliximab group achieved a 74% mean decrease in the PSSI (DeltaPSSI), followed by mean decreases of 61.7%, 53.1% and 53.7% in the ustekinumab, etanercept and adalimumab groups respectively. The differences in the DeltaPSSI were lower at week 48: ustekinumab 94.9%, infliximab 94.3%, etanercept 83.1% and adalimumab 89.0%. The PASI score improved sufficiently in all treatment groups. Infliximab and ustekinumab exhibited greater efficacy at weeks 4 and 12. This difference was not as prominent as that revealed by the PSSI. At week 48, the differences in the DeltaPASI were barely statistically significant (P = 0.048). CONCLUSIONS: All four biologic agents yielded significant improvement in both scalp and skin lesions. Ustekinumab and infliximab exhibited the greatest efficacy, which was clinically meaningful from the early stages of the study. Adalimumab and etanercept followed, yielding satisfactory improvement rates. PMID- 27406437 TI - Aluminum complexes containing biphenolate phosphine ligands: synthesis and living ring-opening polymerization catalysis. AB - This report describes the synthesis, structure, and reactivity of aluminum complexes containing tridentate biphenolate phosphine ligands of the type [RP(2-O 3,5-C6H2tBu2)2]2- (R = tBu (2a), Ph (2b)). Alkane elimination of AlMe3 with one equiv. of H2[2a] or H2[2b] in THF at 0 degrees C cleanly affords colorless crystalline [2a]AlMe(THF) (3a) and [2b]AlMe(THF) (3b), respectively. An X-ray diffraction study of 3a showed it to be a five-coordinate THF-bound species, whose coordination geometry is best described as trigonal bipyramidal, having the phosphorus donor and THF at axial positions. Treatment of either in situ prepared or isolated methyl complexes 3a,b with one equiv. of benzyl alcohol in toluene or THF generated their corresponding benzyloxides {[2a,b]Al(MU2-OCH2Ph)}2 (4a,b). An X-ray diffraction study of 4a revealed a dimeric structure, in which the coordination geometry of aluminum is also distorted trigonal bipyramidal with the tridentate 2a ligand being facially bound. In the presence of one equiv. of benzyl alcohol, complex 3a is a competent catalyst precursor for the living ring opening polymerization of epsilon-caprolactone (epsilon-CL) and rac-lactide (rac LA), producing poly(epsilon-caprolactone) and poly(rac-lactide), respectively, in a controlled manner. As such, well-defined block copolymers of epsilon-CL with rac-LA can also be prepared by catalytic 3a. Kinetic studies revealed that 3a catalyzes the polymerization of rac-lactide at a rate 2-fold faster than that of 3b, indicating the significance of the P-substituent effect on this catalysis. Interestingly, the polymerization rate of rac-lactide by 3a is 16.5 times faster than that of l-lactide under otherwise identical conditions. PMID- 27406436 TI - Deformability of transfused red blood cells is a potent determinant of transfusion-induced change in recipient's blood flow. AB - OBJECTIVE: There is a growing concern regarding the risks in the transfusion of PRBC, as numerous studies have reported negative transfusion outcomes, including reduced blood perfusion. In search of this phenomenon's mechanism, the effect of PRBC deformability, a major determinant of blood flow, on transfusion outcome was explored. METHODS: The effect of PRBC deformability was examined by the transfusion-induced change in recipients' ?SBF, in beta-TM patients, who are routinely treated with lifelong frequent transfusions. SBF was determined using a laser Doppler imager. RESULTS: ?SBF was examined vs PRBC deformability, the transfusion-induced increase in ?Hct and the recipients' SBF before transfusion (SBFB ). ?SBF elevated with increasing PRBC deformability, with a highly significant dependence, while its elevation with ?Hct was much less significant. ?SBF was inversely proportional to the SBFB . CONCLUSIONS: This study provides, for the first time in humans, direct evidence that the deformability of transfused PRBC is a potent effector of transfusion outcome. Currently, PRBC are supplied primarily by the first-in-first-out criteria, while their functionality is ignored. The testing of PRBC hemodynamic quality would introduce a new paradigm into blood banking, which would contribute substantially to improving transfusion therapy. PMID- 27406438 TI - Operative repair of iatrogenic innominate artery to left innominate vein arteriovenous fistula after pacemaker laser lead extraction. PMID- 27406439 TI - Minimally invasive esophagectomy in a 6-year-old girl for the sequelae of corrosive esophagitis. PMID- 27406440 TI - Three-dimensional evaluation of ductal tissue in coarctation of the aorta using X ray phase-contrast tomography. PMID- 27406442 TI - Estimating the probability of underdosing microscopic brain metastases with hippocampal-sparing whole-brain radiation. AB - PURPOSE/OBJECTIVES: Whole-brain radiation for brain metastases can result in cognitive side effects. Hippocampal-sparing techniques have been developed to decrease morbidity, but they carry the risk of underdosing lesions near the hippocampus due to the unavoidable dose gradient from the hippocampal surface to the prescription isodose surface. This study examines the impact of variable levels of hippocampal sparing on the underdosing of potential brain metastases. MATERIALS/METHODS: Helical intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were developed for hippocampal sparing whole-brain treatment. For all plans, 30Gy was prescribed in 10 fractions to result in mean hippocampal doses of 6-12Gy. From a series of expanded shells, we determined the distance from the hippocampus at which the parenchyma would receive less than specified doses. Then, using published data, a mathematical model was constructed to predict the incident probability of potential brain metastases receiving different doses for different levels of hippocampal sparing. RESULTS: Whole-brain radiation plans were able to spare the hippocampi to mean doses of 7-12Gy under our planning constraints; more stringent constraints compromised brain coverage. The dose gradients were ~4% per mm, regardless of the hippocampal constraint, and they decreased sharply by a factor of almost 4 at approximately 15mm from the hippocampi. A mathematical model was constructed and combined the plan information with published data on the distribution of brain metastases, to determine the percentage of potential brain metastases receiving specified doses, as a function of technique and level of hippocampal sparing. CONCLUSIONS: Our results describe the characteristics of an array of hippocampal sparing whole-brain radiation dose distributions. These can be used as a decision making guideline for weighing the benefit of decreased dose to the hippocampi against the cost of decreased dose to potential brain metastases when deciding on a hippocampal-sparing whole-brain irradiation treatment approach. PMID- 27406441 TI - Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer. AB - BACKGROUND AND PURPOSE: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced anal canal carcinoma, although treatment-related side effects can affect patient quality of life (QOL). The purpose was to prospectively evaluate the effects of Tomotherapy (HT) based CCRT on patient reported QOL in locally advanced anal cancer. PATIENTS AND METHODS: Fifty-four patients treated with HT and concurrent 5-fluorouracil/mitomycin-C underwent QOL evaluation at baseline, after treatment, and during follow-up with EORTC core (QLQ-C30) and colorectal (QLQ-CR29) questionnaires. The QOL scores at baseline and post-treatment were compared. RESULTS: All C30 functional symptoms, except emotional and cognitive functioning, were impaired end-of-treatment and recovered by 3months follow-up. The majority of symptom scores were worse end-of-treatment but recovered by 3months except for fecal incontinence (FI), diarrhea, urinary incontinence (UI), and dyspareunia which persisted. FI returned to baseline at 12months while diarrhea, UI, and dyspareunia persisted. CONCLUSIONS: Most impaired functions and symptoms following HT based CCRT were temporary and improved by 3months post-therapy. Late complications affecting QOL were FI, sexual function, UI, and diarrhea. Our observations support routine use of IMRT and emphasize the significance of precise evaluation of sexual, urinary, and anorectal functions before starting CCRT and routine incorporation of QOL evaluations. PMID- 27406443 TI - PrP(c) deficiency and dasatinib protect mouse intestines against radiation injury by inhibiting of c-Src. AB - BACKGROUND & AIM: Despite extensive study of the contribution of cell death and apoptosis to radiation-induced acute intestinal injury, our knowledge of the signaling mechanisms involved in epithelial barrier dysfunction remains inadequate. Because PrP(c) plays a key role in intestinal homeostasis by renewing epithelia, we sought to study its role in epithelial barrier function after irradiation. DESIGN: Histology, morphometry and plasma FD-4 levels were used to examine ileal architecture, wound healing, and intestinal leakage in PrP(c) deficient (KO) and wild-type (WT) mice after total-body irradiation. Impairment of the PrP(c) Src pathway after irradiation was explored by immunofluorescence and confocal microscopy, with Caco-2/Tc7 cells. Lastly, dasatinib treatment was used to switch off the Src pathway in vitro and in vivo. RESULTS: The decrease in radiation-induced lethality, improved intestinal wound healing, and reduced intestinal leakage promoted by PrP(c) deficiency demonstrate its involvement in acute intestinal damage. Irradiation of Cacao2/Tc7 cells induced PrP(c) to target the nuclei associated with Src activation. Finally, the protective effect triggered by dasatinib confirmed Src involvement in radiation-induced acute intestinal toxicity. CONCLUSION: Our data are the first to show a role for the PrP(c)-Src pathway in acute intestinal response to radiation injury and offer a novel therapeutic opportunity. PMID- 27406445 TI - Potential impact of a bedside procedure service on training procedurally competent hospitalists in a community-based residency program. AB - BACKGROUND: The Society of Hospital Medicine has delineated procedures as one of the core competencies for hospitalists. Little is known about whether exposure to a medical procedure service (MPS) impacts the procedural certification rate in internal medicine trainees in a community hospital training program. OBJECTIVE: To determine whether or not exposure to an MPS would impact both the number of procedures performed and the rate of resultant certifications in a community hospital internal medicine training program. DESIGN: Retrospective review. METHODS: Five cohorts of resident physicians and their procedure data were analyzed comparing months where residents were unexposed to the intervention (pre MPS) to months where residents were exposed to the intervention (post-MPS). We calculated the average number of procedures performed per month for pre- versus post-MPS periods. For procedural certification, we compared two proportions: the number of certifications over the number of 6-month pre-MPS periods and the number of certifications over the number of 6-month post-MPS periods. SETTING/SUBJECTS: The study was conducted at a community-based academic medical center. Subjects included all internal medicine residents. RESULTS: We found a statistically significant difference between the groups, with pre-MPS groups performing 4.3 procedures per month compared with post-MPS groups performing 6.7 procedures per month (p=0.0010). For certification rates, we found statistically significant differences in several categories - overall, paracentesis, femoral central lines, and jugular central lines. CONCLUSIONS: This study demonstrated that resident exposure to an MPS statistically significantly increased the total number of procedures performed. This study also showed that overall certification rates were statistically significantly different between the pre- and post-MPS groups for several procedures. PMID- 27406444 TI - Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification. AB - Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells. Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection. This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics. Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively. DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively. Using the Metacore(TM) database, 29 DEPs were enriched in a network involved in p53 regulation. Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection. This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection. PMID- 27406447 TI - Multiple coronary-cameral fistulas to the left ventricle arising from both coronary arteries. AB - Coronary-cameral fistula (CCF) is an anomalous connection between a coronary artery and a cardiac chamber or major vessel, seen in about 0.8% of the cases undergoing coronary angiography. Most patients are asymptomatic and diagnosis is made incidentally during coronary angiography. We present an image case of CCF which was found incidentally during pre-liver transplantation work up. PMID- 27406446 TI - In-hospital and long-term mortality in Takotsubo cardiomyopathy: a community hospital experience. AB - BACKGROUND: Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular dysfunction, frequently precipitated by a stressful event. Despite the favorable course and good long-term prognosis, a variety of complications may occur in the acute phase of the disease. The aim of this study was to evaluate the in-hospital and long-term outcomes of a cohort of TTC patients. METHODS: Fifty-five patients (mean age 68.1+/-12 years) were prospectively followed for a mean of 69.6+/-32.2 months (64,635 days). In-hospital (death, heart failure, arrhythmias) and long-term events (death and recurrences) were recorded. RESULTS: Patients were predominantly women (87.3%) who experienced a recent stressful event (emotional or physical) and were admitted to hospital for chest pain. Eleven patients (20%) had a diagnosis of depressive disorder, and arterial hypertension was the most frequent cardiovascular risk factor. The ECG revealed ST-segment elevation in 43.6% of patients. At angiography, seven cases (12.7%) had at least one significant (>=50%) coronary artery stenosis and four patients (7.3%) had myocardial bridging of the left anterior descending artery. During hospitalization, three patients died (one from cardiac causes) and cardiovascular complications occurred in 12 patients. During follow-up, five patients died (none from cardiac causes), six patients had recurrences within the first year. Two patients had two recurrences: one after 114 days, triggered by an asthma attack as the first event, and the other after 1,850 days. CONCLUSIONS: In TTC patients, in-hospital and long-term mortality is primarily due to non-cardiovascular causes. Recurrences are not infrequent and coronary artery disease is not an uncommon finding. PMID- 27406448 TI - QRS fragmentation: its role in sherlocking the arrhythmogenic heart. AB - The electrocardiogram (ECG) is a commonly available basic diagnostic modality in in-patient, out-patient, and emergency departments. In patients with coronary artery disease (CAD), the presence of a fragmented QRS (f-QRS), which is an extra R wave (R'), notching of the single R wave, notching of the S wave in at least two contiguous leads on the 12-lead ECG, is associated with a myocardial scar from previous myocardial injury. Furthermore, the presence of f-QRS has been shown to be associated with adverse outcomes in CAD and non-CAD patients. In the present paper, we will solely focus on the usefulness and utilization of f-QRS in predicting ventricular tachyarrhythmia in many heart diseases, that is, ischemic cardiomyopathy, non-ischemic cardiomyopathy, hypertrophic obstructive cardiomyopathy, Brugada syndrome, and arrhythmogenic right ventricular cardiomyopathy. In the majority of such cases, ventricular tachyarrhythmia results in sudden cardiac death. Diagnosing them beforehand can lead to prevention and/or early treatment of these arrhythmias to prevent potential morbidity and mortality. PMID- 27406449 TI - A rare case of carcinoid tumor in a tailgut cyst. AB - Tailgut cysts are rare congenital lesions that arise from the failure of regression of the embryological tailgut. We report a case of neoplastic transformation of tailgut cyst to carcinoid tumor which is exceedingly uncommon. PMID- 27406450 TI - Celiac disease unmasked by acute severe iron deficiency anemia. AB - The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID- 27406451 TI - A case of right atrial thrombus secondary to hepatocellular carcinoma. PMID- 27406452 TI - Coronary artery disease in patients with body mass index >=30 kg/m(2): a retrospective chart analysis. AB - OBJECTIVE: In this study, we evaluated obesity as a single risk factor for coronary artery disease (CAD), along with the synergistic effect of obesity and other risk factors. METHODS: A retrospective study of 7,567 patients admitted to hospital for chest pain from 2005 to 2014 and underwent cardiac catheterization. Patients were divided into two groups: obese and normal with body mass index (BMI) calculated as >=30 kg/m(2) and <25, respectively. We assessed the modifiable and non-modifiable risk factors in obese patients and the degree of CAD. RESULTS: Of the 7,567 patients who underwent cardiac catheterization, 414 (5.5%) had a BMI >=30. Of 414 obese patients, 332 (80%) had evidence of CAD. Obese patients displayed evidence of CAD at the age of 57 versus 63.3 in non obese patients (p<0.001). Of the 332 patients with CAD and obesity, 55.4% had obstructive CAD versus 44.6% with non-obstructive CAD. In obese patients with CAD, male gender and history of smoking were major risk factors for development of obstructive CAD (p=0.001 and 0.01, respectively) while dyslipidemia was a major risk factor for non-obstructive CAD (p=0.01). Additionally, obese patients with more than one risk factor developed obstructive CAD compared to non obstructive CAD (p=0.003). CONCLUSION: Having a BMI >=30 appears to be a risk factor for early development of CAD. Severity of CAD in obese patients is depicted on non-modifiable and modifiable risk factors such as the male gender and smoking or greater than one risk factor, respectively. PMID- 27406453 TI - An uncommon cause of chest pain - penetrating atherosclerotic aortic ulcer. AB - Chest pain is a very common symptom and can be of cardiac or non-cardiac origin. It accounts for approximately 5.5 million annual emergency room visits in the United States, according to 2011 CDC data. Penetrating atherosclerotic aortic ulcer (PAU), an uncommon condition, is also a potential cause of chest pain. We here report the case of a 65-year-old woman who presented with atypical chest and back pain. The pain persisted for 4 weeks necessitating two emergency room visits. Initial tests were non-significant including cardiac troponins, an electrocardiogram (EKG), and a chest X-ray on her first visit. Upon her second visit, she underwent a computed tomography angiogram of chest with contrast which revealed a PAU with an intramural hematoma in descending aorta. The PAU was finally diagnosed with an exclusion of other chest pain causes. She was treated non-surgically with a blood pressure control strategy and pain management. After a 2-month period of smoking cessation and following the achievement of a controlled blood pressure, she felt well without chest pain. PMID- 27406454 TI - Hyperpigmentation in a middle aged woman: a common yet underdiagnosed condition. PMID- 27406455 TI - Oral verrucous hyperplasia due to repetitive chewing on lips. PMID- 27406456 TI - Diagnostic testing: a key component of high-value care. AB - This is the fourth article of a series on fundamental concepts in biostatistics and research. In this article, the author reviews the fundamental concepts in diagnostic testing, sensitivity, and specificity and how they relate to the concept of high-value care. The topics are discussed in common language, with a minimum of jargon and mathematics, and with clinical examples. Emphasis is given to conceptual understanding. A companion article will follow focusing on predictive value and prior probability. PMID- 27406457 TI - Metastatic right ventricular mass with intracavitary obliteration. AB - Metastatic cardiac tumors are more common than the primary cardiac tumors. Cervical cancer metastasizing outside of the pelvis is commonly spread to the lungs, liver, bones and lymph nodes than to the heart. Right-sided metastasis to the heart is more common than to the left side. Intramural spread is more common than intracavitary growth of metastatic cardiac tumors leading to delayed clinical presentation. Intracavitary mass can be confused with intracavitary thrombus which can be seen in the setting of pulmonary embolism. Transthoracic echocardiography plays a major role in the decision making and management of pulmonary embolism, and this modality can also be used to diagnose cardiac masses. Other modalities like TEE, cardiac CT, cardiac MRI and PET-CT scan have further utility in delineating these masses. This may help to plan appropriate management of the right ventricular mass particularly in cases where the patient history and CT pulmonary angiography results favor the diagnosis of pulmonary embolism. We present the case of a 49-year-old woman with a history of supracervical hysterectomy and salpingo-oophorectomy on oral estrogen therapy who was admitted with complaints of pleuritic chest pain and respiratory insufficiency after a long flight. Initial work-up showed sub-segmental pulmonary embolus in the right posterior lower lobe pulmonary artery, and the patient was managed on intravenous heparin. Lack of appropriate response to standard therapy led to further evaluation. Multimodality imaging and biopsies revealed a large right intracavitary ventricular metastatic squamous cell tumor, with the cervix as the primary source. PMID- 27406458 TI - Primary squamous cell carcinoma of the rectum: a case report and literature review. AB - Squamous cell carcinoma (SCC) of the rectum is a rare occurrence with an incidence rate of 0.1-0.25% per 1,000 cases. Herein, we report a case of a 52 year-old female who presented with a 2-month history of diffuse lower abdominal pain and hematochezia. Abdominal CT scan revealed a 7-cm irregular rectal mass, and the biopsy showed SCC. PMID- 27406460 TI - Permanent hypopigmentation after triamcinolone injection for tennis elbow. PMID- 27406459 TI - Hypertriglyceridemic pancreatitis associated with confounding laboratory abnormalities. AB - We present the case of a 36-year-old woman who presented to our hospital with epigastric abdominal pain and tenderness. Laboratory evaluation identified high lipase, normal amylase, pseudohyponatremia, and relatively falsely low triglyceride levels (initial value of 2,329 mg/dl which on repeat was found to have corrected value of >10,000 mg/dl). The overall clinical picture was consistent with acute pancreatitis due to hypertriglyceridemia. The patient was commenced on IV insulin and eventually required plasmapheresis with good clinical outcome. This case highlights the importance of being cognizant of falsely low amylase and TG levels that can be present in patients with hypertriglycereidemic pancreatitis. PMID- 27406461 TI - Disseminated gonococcal infection: an unusual presentation. AB - Gonococcus typically affects the mucosal surfaces but in rare cases can spread to bloodstream causing disseminated gonococcal infection (DGI). The usual presentation of DGI is rash, polyarthralgia, and tenosynovitis. We present the case of a 23-year-old female who presented to our hospital with pustular rash and tenosynovitis of hand and was sent home on Augmentin. Her symptoms worsened despite treatment and she presented back to the ED. On investigation, she was found to have DGI and was appropriately treated. DGI should be kept in mind in sexually active youngsters who have only one or two features of the classic triad of rash, tenosynovitis, and arthritis. Timely management and appropriate treatment of DGI is very important to avoid complications and morbidity. PMID- 27406462 TI - Effects of colchicine on pericardial diseases: a review of the literature and current evidence. AB - Colchicine, extracted from the colchicum autumnale plant, used by the ancient Greeks more than 20 centuries ago, is one of the most ancient drugs still prescribed even today. The major mechanism of action is binding to microtubules thereby interfering with mitosis and subsequent modulation of polymorphonuclear leukocyte function. Colchicine has long been of interest in the treatment of cardiovascular disease; however, its efficacy and safety profile for specific conditions have been variably established in the literature. In the subset of pericardial diseases, colchicine has been shown to be effective in recurrent pericarditis and post-pericardiotomy syndrome (PPS). The future course of treatment and management will therefore highly depend on the results of the ongoing large randomized placebo-controlled clinical trial to evaluate the efficacy and safety of colchicine for the primary prevention of several postoperative complications and in the perioperative period. Also, given the positive preliminary outcomes of colchicine usage in pericardial effusions, the future therapeutical use of colchicine looks promising. Further study is needed to clarify its role in these disease states, as well as explore other its role in other cardiovascular conditions. PMID- 27406463 TI - An uncommon complication of a common clinical scenario: exploring reexpansion pulmonary edema with a case report and literature review. AB - Reexpansion pulmonary edema (RPE) is a rare complication that can occur after rapid reinflation of the lung following thoracentesis of a pleural effusion or chest tube drainage of pneumothorax. The severity in clinical presentation can be widely varied from radiographic changes only to rapidly progressive respiratory failure requiring mechanical ventilation. The quick nature of onset and potential for serious decline in a previously stable patient makes it important to prepare, recognize, diagnose, and appropriately manage patients who develop RPE. The standard treatment for RPE consists of supportive care, and there are certain measures that may be taken to reduce the risk, including limiting the amount drained and avoiding excessive negative pleural pressure. Exactly how to prevent RPE remains unclear, however, and varying recommendations exist. This is a case report of RPE after thoracentesis for a pleural effusion and a brief review of literature to date, including potential preventative strategies. PMID- 27406465 TI - A Network Flow Analysis of the Nitrogen Metabolism in Beijing, China. AB - Rapid urbanization results in high nitrogen flows and subsequent environmental consequences. In this study, we identified the main metabolic components (nitrogen inputs, flows, and outputs) and used ecological network analysis to track the direct and integral (direct + indirect) metabolic flows of nitrogen in Beijing, China, from 1996 to 2012 and to quantify the structure of Beijing's nitrogen metabolic processes. We found that Beijing's input of new reactive nitrogen (Q, which represents nitrogen obtained from the atmosphere or nitrogen containing materials used in production and consumption to support human activities) increased from 431 Gg in 1996 to 507 Gg in 2012. Flows to the industry, atmosphere, and household, and components of the system were clearly largest, with total integrated inputs plus outputs from these nodes accounting for 31, 29, and 15%, respectively, of the total integral flows for all paths. The flows through the sewage treatment and transportation components showed marked growth, with total integrated inputs plus outputs increasing to 3.7 and 5.2 times their 1996 values, respectively. Our results can help policymakers to locate the key nodes and pathways in an urban nitrogen metabolic system so they can monitor and manage these components of the system. PMID- 27406464 TI - AgNO3 dependant modulation of glucose mediated respiration kinetics in Escherichia coli at different pH and temperature. AB - The inhibitory role of AgNO3 on glucose-mediated respiration in Escherichia coli has been investigated as a function of pH and temperature using Clark-type electrode, environmental scanning electron microscopy, and computational tools. In the given concentration of bacterial suspension (1 * 108 CFU/ml), E. coli showed an increasing nonlinear trend of tetra-phasic respiration between 1-133 MUM glucose concentration within 20 min. The glucose concentrations above 133 MUM did not result any linear increment in respiration but rather showed a partial inhibition at higher glucose concentrations (266-1066 MUM). In the presence of glucose, AgNO3 caused a concentration-dependent (47-1960 MUM) inhibition of the respiration rate within 4 min of its addition. The respiration rate was the highest at pH 7-8 and then was decreased on either side of this pH range. The inhibitory action of AgNO3 upon bacterial respiration was the highest at 37 degrees C. The observations of the respiration data were well supported by the altered bacterial morphology as observed in electron microscopic study. Docking study indicated the AgNO3 binding to different amino acids of all respiratory complex enzymes in E. coli and thereby explaining its interference with the respiratory chain. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406466 TI - Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases. AB - BACKGROUND AND OBJECTIVES: Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases. METHODS: Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded. RESULTS: Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC. CONCLUSION: Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. (c) 2016 Wiley Periodicals, Inc. PMID- 27406467 TI - Development of near-zero water consumption cement materials via the geopolymerization of tektites and its implication for lunar construction. AB - The environment on the lunar surface poses some difficult challenges to building long-term lunar bases; therefore, scientists and engineers have proposed the creation of habitats using lunar building materials. These materials must meet the following conditions: be resistant to severe lunar temperature cycles, be stable in a vacuum environment, have minimal water requirements, and be sourced from local Moon materials. Therefore, the preparation of lunar building materials that use lunar resources is preferred. Here, we present a potential lunar cement material that was fabricated using tektite powder and a sodium hydroxide activator and is based on geopolymer technology. Geopolymer materials have the following properties: approximately zero water consumption, resistance to high- and low-temperature cycling, vacuum stability and good mechanical properties. Although the tektite powder is not equivalent to lunar soil, we speculate that the alkali activated activity of lunar soil will be higher than that of tektite because of its low Si/Al composition ratio. This assumption is based on the tektite geopolymerization research and associated references. In summary, this study provides a feasible approach for developing lunar cement materials using a possible water recycling system based on geopolymer technology. PMID- 27406469 TI - Application of force-length curve for determination of leg stiffness during a vertical jump. AB - PURPOSE: The aim of this study was to present the methodology for estimation of a leg stiffness during a countermovement jump. The question was asked whether leg stiffness in the countermovement and take-off phases are similar to each other as demonstrated in previous reports. It was also examined whether the stiffness in left lower limb is similar to the one in right lower limb. METHODS: The research was conducted on 35 basketball players. Each participant performed three countermovement jumps with arm swing to the maximum height. Measurements employed a Kistlerforce plate and a BTS SMART system for motion analysis. Leg stiffness (understood as an inclination of the curve of ground reaction forces vs. length) was computed for these parts of countermovement and take-off phases where its value was relatively constant and F(Deltal) relationship was similar to linear. RESULTS: Mean value (+/-SD) of total stiffness of both lower limbs in the countermovement phase was 7.1 +/- 2.3 kN/m, whereas this value in the take-off phase was 7.5 +/- 1 kN/m. No statistically significant differences were found between the leg stiffness in the countermovement and the take-off phases. No statistically significant differences were found during the comparison of the stiffness in the right and left lower limb. CONCLUSIONS: The calculation methodology allows us to estimate the value of leg stiffness based on the actual shape of F(Deltal) curve rather than on extreme values of DeltaF and Deltal. Despite different tasks of the countermovement and the take-off phases, leg stiffness in these phases is very similar. Leg stiffness during a single vertical jump maintains a relatively constant value in the parts with a small value of acceleration. PMID- 27406468 TI - Landscape determinants of fine-scale genetic structure of a small rodent in a heterogeneous landscape (Hluhluwe-iMfolozi Park, South Africa). AB - Small mammals provide ecosystem services, acting, for example, as pollinators and seed dispersers. In addition, they are also disease reservoirs that can be detrimental to human health and they can also act as crop pests. Knowledge of their dispersal preferences is therefore useful for population management and landscape planning. Genetic data were used alongside landscape data to examine the influence of the landscape on the demographic connectedness of the Natal multimammate mouse (Mastomys natalensis) and to identify landscape characteristics that influence the genetic structure of this species across a spatially and temporally varying environment. The most significant landscape features shaping gene flow were aspect, vegetation cover, topographic complexity (TC) and rivers, with western facing slopes, topographic complexity and rivers restricting gene flow. In general, thicket vegetation was correlated with increased gene flow. Identifying features of the landscape that facilitate movement/dispersal in M. natalensis potentially has application for other small mammals in similar ecosystems. As the primary reservoir host of the zoonotic Lassa virus, a landscape genetics approach may have applications in determining areas of high disease risk to humans. Identifying these landscape features may also be important in crop management due to damage by rodent pests. PMID- 27406470 TI - The etiology of social anxiety disorder: An evidence-based model. AB - The current paper presents an update to the model of social anxiety disorder (social phobia) published by Rapee and Spence (2004). It evaluates the research over the intervening 11 years and advances the original model in response to the empirical evidence. We review the recent literature regarding the impact of genetic and biological influences, temperament, cognitive factors, peer relationships, parenting, adverse life events and cultural variables upon the development of SAD. The paper draws together recent literature demonstrating the complex interplay between these variables, and highlights the many etiological pathways. While acknowledging the considerable progress in the empirical literature, the significant gaps in knowledge are noted, particularly the need for further longitudinal research to clarify causal pathways, and moderating and mediating effects. The resulting model will be valuable in informing the design of more effective treatment and preventive interventions for SAD and will provide a useful platform to guide future research directions. PMID- 27406471 TI - Interaction of glucose-derived carbon quantum dots with silver and gold nanoparticles and its application for the fluorescence detection of 6 thioguanine. AB - The interaction of glucose-derived carbon quantum dots (CQDs) with silver (Ag) and gold (Au) nanoparticles (NPs) was explored by fluorescence spectroscopy. Both metal NPs cause an efficient quenching of CQD fluorescence, which is likely due to the energy transfer process between CQDs as donors and metal NPs as acceptors. The Stern-Volmer plots were evaluated and corresponding quenching constants were found to be 1.9 * 1010 and 2.2 * 108 M-1 for AgNPs and AuNPs, respectively. The analytical applicability of these systems was demonstrated for turn-on fluorescence detection of the anti-cancer drug, 6-thioguanine. Because the CQD AgNP system had much higher sensitivity than the CQD-AuNP system, we used it as a selective fluorescence probe in a turn-on assay of 6-thioguanine. Under optimum conditions, the calibration graph was linear from 0.03 to 1.0 MUM with a detection limit of 0.01 MUM. The developed method was applied to the analysis of human plasma samples with satisfactory results. PMID- 27406472 TI - Non-covalent pomegranate (Punica granatum) hydrolyzable tannin-protein complexes modulate antigen uptake, processing and presentation by a T-cell hybridoma line co-cultured with murine peritoneal macrophages. AB - In this work we characterize the interaction of pomegranate hydrolyzable tannins (HT) with hen egg-white lysozyme (HEL) and determine the effects of non-covalent tannin-protein complexes on macrophage endocytosis, processing and presentation of antigen. We isolated HT from pomegranate and complex to HEL, the resulting non covalent tannin-protein complex was characterized by gel electrophoresis and MALDI-TOF MS. Finally, cell culture studies and confocal microscopy imaging were conducted on the non-covalent pomegranate HT-HEL protein complexes to evaluate its effect on macrophage antigen uptake, processing and presentation to T-cell hybridomas. Our results indicate that non-covalent pomegranate HT-HEL protein complexes modulate uptake, processing and antigen presentation by mouse peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a non-covalent pomegranate HT-HEL complex had already reached maximum IL-2 expression. Pomegranate HT may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas. PMID- 27406473 TI - Applications of water stable metal-organic frameworks. AB - The recent advancement of water stable metal-organic frameworks (MOFs) expands the application of this unique porous material. This review article aims at studying their applications in terms of five major areas: adsorption, membrane separation, sensing, catalysis, and proton conduction. These applications are either conducted in a water-containing environment or directly targeted on water treatment processes. The representative and significant studies in each area were comprehensively reviewed and discussed for perspectives, to serve as a reference for researchers working in related areas. At the end, a summary and future outlook on the applications of water stable MOFs are suggested as concluding remarks. PMID- 27406474 TI - DH must ditch short-sighted plans to axe nurse advisers. AB - Specialist care requires specialist services staffed by nurses and doctors who are experts in their field. NHS England is striving to make this more likely for patients with congenital heart disease by concentrating services in a smaller number of trusts, which will therefore deal with more cases and develop staff expertise further. PMID- 27406475 TI - UK is 'unprepared' for predicted nurse shortages. AB - The UK is heading for a major nursing shortage because it has failed to deal with the challenges of an ageing workforce and reliance on overseas staff, the RCN has said. PMID- 27406477 TI - Decisions on safe staffing and ratios should be made locally, says guidance. AB - Safe staffing decisions should be made locally and not be governed by ratios. PMID- 27406476 TI - Nursing on TV. AB - TV presenter Myleene Klass followed in her mother's footsteps for a documentary series on the NHS. PMID- 27406478 TI - 'Rethink plans' to cut heart surgery centres. AB - A matron on a cardiac unit which has been told it can no longer perform children's heart surgery has urged a rethink of the move. PMID- 27406479 TI - Funding cuts 'would put specialist training at risk'. AB - Senior nurses have warned that post-registration training programmes for district and school nurses in England could be closed amid uncertainty over funding. PMID- 27406480 TI - New national guardian for whistleblowers. AB - An NHS England medical director has been appointed to the national whistleblowing guardian role, replacing nurse Dame Eileen Sills, who resigned aft er just two months. PMID- 27406484 TI - 'The nurse advisers DH intends to scrap would be invaluable during Brexit talks,' argues policy expert. AB - An international nursing expert has urged the Department of Health to delay plans to axe its team of nurse advisers, following the Brexit vote. PMID- 27406482 TI - Students with children will be hardest hit by fees. AB - Nursing students with children could lose more than L100 a month under government plans to change healthcare education funding, new research suggests. PMID- 27406486 TI - Patient mortality rates are better with higher proportion of graduate nurses. AB - Patients are more likely to survive when nurses who care for them have a degree, research has revealed. PMID- 27406487 TI - NMC to examine impact of fitness to practise hearings. AB - A project to understand the impact of fitness to practise (FtP) investigations on nurses' mental health is about to get under way at the Nursing and Midwifery Council. The nursing regulator says it is committed to undertaking work to 'better understand' the link between mental health and the investigation process. PMID- 27406490 TI - Anxiety. AB - Essential facts Anxiety is the feeling of fear that occurs when faced with threatening or stressful situations. It is a normal response when confronted with danger, but, if it is overwhelming or the feeling persists, it could be regarded as an anxiety disorder. The Royal College of Psychiatrists says anxiety disorders, including panic disorder, post-traumatic stress disorder and social anxiety disorder, affect about one in ten. PMID- 27406491 TI - Alcohol restrictions have effect on public health. AB - The largest study looking at the link between alcohol and cardiovascular disease shows laws restricting alcohol sales in an American state have had measurable public health effects. PMID- 27406492 TI - Better-educated women more likely to spot breast cancer. AB - Women with fewer qualifications are less likely to spot warning signs of breast cancer, according to a study funded by Cancer Research UK. PMID- 27406494 TI - Cancer campaigns should target ethnic groups. AB - Tailoring campaigns to different cultures could encourage more people from ethnic groups to get cancer symptoms checked out earlier, say researchers. PMID- 27406495 TI - New mums who smoke at lowest level for ten years. AB - The proportion of new mothers in England who smoke has fallen to the lowest level since relevant statistics were first published almost ten years ago, dipping below the national target. PMID- 27406496 TI - Brexit: What now for nurses? AB - The NHS was at the centre of some of the most heated arguments during the run-up to the EU referendum. There were claims and counterclaims about how much money could be diverted from the UK's EU contributions to support it, and concerns about how it could manage without EU staff. PMID- 27406497 TI - Making a role for nurses in CCGs. AB - What do nurses in clinical commissioning groups (CCGs) do? The answer is lots, but their role and influence varies greatly between CCGs. In May, a report from NHS Clinical Commissioners (NHSCC) - the membership organisation of CCGs - highlighted the key responsibilities of nurses and the important contribution they make in what are often pressured and demanding roles (see tinyurl.com/CCG nurses ). PMID- 27406498 TI - The benefits of keeping track. AB - Barcodes are familiar to everyone from their supermarket shop, but the potential they offer for improving health care in the NHS is only just being explored. PMID- 27406499 TI - Brexit will boost pay. AB - Now that we are leaving the European Union we will have more control of our health service. This will allow us to increase the resources available and ensure we have the medical staff needed to keep it running. PMID- 27406500 TI - Mixed messages fuel uncertainty over Brexit. AB - You do a brilliant job for your patients, you are a crucial part of our NHS, and as a country we value you.' PMID- 27406501 TI - Think 'family' to give every child the best start in life. AB - Ensuring children get the best start in life is critical for building healthy, resilient and capable children, young people and adults. PMID- 27406502 TI - A century of stigma. AB - You will I am sure be aware that the RCN is celebrating its centenary this year. Much has been done to recognise the achievements of the RCN since its inception in 1916, and rightly so. PMID- 27406506 TI - Thank you for your support. AB - I would like to give my heartf elt thanks to all your readers who supported the Mary Seacole Memorial Statue Appeal over the past 12 years. PMID- 27406503 TI - Seacole event so inspirational. AB - I was at the unveiling of the statue of Mary Seacole. PMID- 27406507 TI - Austerity is a choice. AB - Our NHS is in a financial crisis, with nine in ten hospitals overspent as a result of years of funding squeezes. PMID- 27406508 TI - Readers' panel - Will nurses be put at risk in the workplace following Brexit? AB - Our experts consider a hot topic of the day. PMID- 27406509 TI - When best-laid plans unravel. AB - I need to streamline my practice, I thought. If I halve time spent on pre operative assessment, more patients will get through the system, which means fewer people hanging around as their cataracts worsen. PMID- 27406510 TI - ECG - Cases, Exams, Quizzes and Tutorial for Continuing Medical Education. AB - There are plenty of ECG apps around, but the variety of options can make it difficult to decide which one to plump for. PMID- 27406513 TI - No more suffering in silence. AB - I have been a humanitarian volunteer for more than ten years, in the UK and abroad. While working at a destitution centre in London - which provided the local population, including refugees and asylum seekers, with practical support and advice on accessing health, legal and other services - a client told me she had been a victim of human trafficking. PMID- 27406514 TI - My non-verbal communication skills made a big difference. AB - Towards the end of the second year of my child nursing degree, I worked on a general paediatric ward. One day a teenage girl was admitt ed with high blood glucose levels. PMID- 27406515 TI - Overweight? Your chances of getting a job are reduced. AB - Nurses who are obese need to be aware that their weight could be damaging their careers as well as their health. PMID- 27406516 TI - Finding your voice in a multidisciplinary team. AB - To provide safe and effective person-centred care, nurses have to communicate with a broad range of professionals from different care settings, working collaboratively to share best practice. PMID- 27406517 TI - 'Experience what you can'. AB - Christine Jones, 54, has more than 30 years' nursing experience. Married with two children, she has been a lung cancer clinical nurse specialist for 10 years. Last month she became Mesothelioma UK's 10th addition to their dedicated team of clinical nurse specialists when she took up her role at Derriford Hospital in Plymouth. PMID- 27406518 TI - How to write a reflective account for revalidation. AB - Rationale and key points This is the fifth in a series of eight articles providing information about the Nursing and Midwifery Council (NMC) revalidation process. This article focuses on preparing five written reflective accounts for revalidation. " Reflective practice encourages nurses and midwives to use their learning to identify areas for improvement. " Reflective practice encourages nurses and midwives to relate their learning to the NMC code of professional standards of practice and behaviour. Reflective activity 'How to' revalidate articles can help to update your practice and provide information about the revalidation process, including how you can record and evidence CPD for revalidation. Reflect on and write a short account of: 1. How recording and evidencing CPD will demonstrate the skills, knowledge and experience you have gained in practice. 2. How you could use this article to educate your colleagues. Subscribers can update their reflective accounts at: rcni.com/portfolio. PMID- 27406519 TI - Parish nursing: an innovative community nursing service. AB - This article explains the concept of parish nursing and provides a historical perspective of this service. It describes the development of a parish nursing service in Heartsease, Norwich, which complements community nursing practice by focusing on the importance of providing spiritual care alongside physical, psychological and social care. Case studies are provided to illustrate the benefits of a parish nursing service to individuals and the community. PMID- 27406521 TI - Malnutrition and dementia. AB - What was the nature of the CPD activity and/or practice-related feedback and/or event or experience in your practice? The CPD article outlined the effects dementia may have on a person's ability to eat and drink safely. It discussed assessment tools to identify patients at risk of malnutrition and management strategies to help maintain nutritional intake. PMID- 27406520 TI - An overview of diabetes. AB - Healthcare professionals in all settings increasingly encounter people with diabetes. Suboptimal control of diabetes may have harmful effects on multiple systems in the body and can result in life-changing and life-threatening complications. Therefore, it is crucial that all healthcare professionals have an understanding of diabetes. This article considers the increase in people developing diabetes worldwide. It defines type 1 and type 2 diabetes and discusses the associated pathophysiology and predisposing factors. The article outlines the basis for the development of the typical signs and symptoms associated with high blood glucose levels. Current guidelines for diagnosing a person with diabetes are considered. PMID- 27406522 TI - 'An utterly amazing nurse'. AB - After three days of worry about my two-year-old daughter, Rosie (pictured), who had become very unwell from chickenpox, we arrived at the emergency department. Previously, three GPs had told us she was fine: she was 'attention seeking' and I was 'exhausted'. The paramedic who arrived at our home told me he wasn't worried about her. But thankfully he acknowledged my concern and took her to hospital. PMID- 27406523 TI - Online. AB - 'There is a disconnect between theory and practice. There is room in research for people of different interests, backgrounds and experiences, and nurses have as much to contribute to academic and research environments as anyone else'. PMID- 27406524 TI - Digital skills training. AB - Can a move to digital transform caring? Deidre Wild and Angela Kydd writing in Nursing Older People discuss how digital skills training in care homes has opened up opportunities for care staff. PMID- 27406525 TI - Career mobility integral to cancer nursing. AB - Why do many nurses find career progression difficult? Nicola James, writing in Cancer Nursing Practice, encourages nurses to consider why they do not benefit from mobility as much as other health professionals, such as doctors. PMID- 27406526 TI - Nutrition. AB - Could a computer nurse improve patients' knowledge of acute heart disease symptoms? Nursing lecturers in Australia have developed an app to teach patients the warning signs. PMID- 27406527 TI - Benefits of a short stay unit. AB - Constance Gray and Martin Christensen write in Nursing Children and Young People on the positive impact of opening a short stay unit. PMID- 27406538 TI - National Speakers. PMID- 27406528 TI - Activation of inflammatory immune gene cascades by lipopolysaccharide (LPS) in the porcine colonic tissue ex-vivo model. AB - The technique of challenging postmortem tissue explants with inflammation inducer such as lipopolysaccharide (LPS) followed by gene expression analysis is used widely for evaluating the immune-suppressing effect of bioactives. Using porcine colonic tissue as an ex-vivo model of mammalian intestinal gut, this study evaluated the effect of incubation time on the integrity of gene transcripts and activation of inflammatory immune gene cascade by LPS treatment. Post-slaughter colon was removed surgically and explants were incubated for 0, 3, 6 and 12 h and the abundance of mRNA transcripts of a panel of 92 immune genes were evaluated using quantitative polymerase chain reaction (qPCR) arrays. The mRNA transcripts were highly intact after 0 and 3 h of incubation; however, after 6 h the degradation was clearly evident. Following 3 h incubation, 98.8% and 100% mRNA transcripts were detectable in the colonic tissue harvested from weaned and mature pigs, respectively. In the explants of weaned piglets, LPS treatment activated inflammatory signalling pathways [high mobility group B1 (HMGB1), dendritic cell maturation, interleukin (IL)-6, IL-8, IL-17F], while these pathways were inhibited by dexamethasone treatment. Activations of inflammatory genes were also evident in the explants collected from the mature pigs subjected to ex-vivo incubation for 3 h in the absence or presence of LPS. It is concluded that the colonic explant remains physiologically viable and responsive to immunological challenge for up to 3 h ex-vivo. PMID- 27406529 TI - Contemporary public perceptions of nursing: a systematic review and narrative synthesis of the international research evidence. AB - AIM: To investigate the current public understanding and perceptions of nursing. BACKGROUND: In recent years, attention to large scale health-care failures has focused considerable concern upon nursing standards. To avoid short-term solutions, and the temptation to see individual failures as representative of the wider profession, it is important to understand contemporary public perceptions of nursing. EVALUATION: A systematic review and narrative synthesis of peer reviewed papers from January 2010 to September 2015. KEY ISSUES: Four main themes were identified: (1) media portrayal of nursing as a troubled profession; (2) entertainment value in demeaning nursing; (3) role incongruity - nursing trusted but not respected; and (4) nursing roles remain poorly understood. CONCLUSIONS: Although there is evidence of strong public trust, this does not generally appear to be born out of an understanding of nursing work and impact; rather it appears to stem from the respect held for the traditional, more sentimental stereotypes of selfless, hardworking young females. IMPLICATIONS FOR NURSING MANAGEMENT: A long-term, strategic solution is required that focuses on public engagement and interaction with the profession in a context wider than personal health/ill health, and that goes beyond the marketing campaigns seen in the past to address recruitment crises. PMID- 27406543 TI - Invited Presentations and Oral Abstracts. PMID- 27406545 TI - Poster Abstracts - Bladder; Renal; Testicular; Supportive Care and Translational Research. PMID- 27406544 TI - Poster Abstracts - Prostate. PMID- 27406546 TI - Sponsor Profiles. PMID- 27406547 TI - Polyunsaturated Fatty Acids and Disease-associated and Cytokine-induced Neurological Manifestations. AB - Fish oil supplementation is suggested as possible mean to improve neurological manifestations of chronic diseases and cytokine immunotherapies. Preclinical and clinical studies show that fish oil supplementation seems able to reduce disease associated anorexia and body weight loss. This improvement could be due to shifts in metabolism and changes in proinflammatory cytokine production and action. omega-3 Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid, are used as substrates for eicosanoid synthesis, competing for enzymes with arachidonic acid, which is a substrate for the synthesis of proinflammatory immunomodulators, such as prostaglandin E2. Fish oil supplementation is generally found to lower production of cytokines including interleukin-1 and tumor necrosis factor-alpha, thereby reducing various immune responses, including inflammation. However, conflicting results regarding the effects of fish oil interventions have been reported. The main factor that emerges from the contradictory reports is the variety of models, assays and methodologies that have been used. This brief review presents an overall perspective on the potential use of omega-3 PUFAs as a nutritional intervention to ameliorate disease-associated and cytokine-induced neurological manifestations. We conclude that substantial further research is required to understand the exact nature of n-3 PUFA-induced immunomodulation in health and disease. PMID- 27406548 TI - Dietary History Affects the Potency of Chronic Opioid Receptor Subtype Antagonist Effects upon Body Weight in Rats. AB - Body weight of rats placed acutely on a palatable diet is significantly reduced following chronic administration of MU (9%), kappa1 (3%) or delta2 (6%) opioid antagonists. Whereas weight loss is comparable in lean Zucker rats (8-11%) following these antagonists, greater weight loss occurs in genetically-obese Zucker rats following chronic MU (10%) and delta2 (7%), relative to kappa1 (2%) antagonism. The present study examined whether rats exposed to high-energy diets (6 weeks) that were either high-carbohydrate or high-fat displayed differential weight and intake reductions following chronic (7 days) daily central administration of equimolar doses (5,20,40 nmol) of selective MU(beta funaltrexamine), kappa1 (nor-binaltorphamine) or delta2 (naltrindole isothiocyanate) opioid antagonists. The high-fat diet stimulated significantly greater weight gain (165 g) than the high-carbohydrate diet. Greater magnitudes and potencies of weight loss were noted for the high-fat diet following MU (11.5%, 3.0 nmol), delta2 (8.4%, 0.01 nmol) and kappa1 (6.2%, 17.8 nmol) antagonists relative to the high-carbohydrate diet MU: 5.8%, 27.5 nmol; delta2: 1.3%, >1000 nmol; kappa1: 2.4%, >1000 nmol). Antagonist-induced weight losses in either dietary group could not be predicted by corresponding intake alterations. These data underscore the importance of dietary history in mediating opioid antagonist effects upon weight, and establishes the MU receptor as the most consistent opioid mediator of weight control. PMID- 27406549 TI - Effect of Carbohydrates and Caffeine on Plasma Amino Acids, Neuroendocrine Responses and Performance in Tennis. AB - Effects of carbohydrate (CHO) and caffeine (CAF) in amounts typically found in sports-drinks on plasma metabolites, neuroendocrine responses and performance in tennis were investigated in 8 skilled players during a 4 h tennis match. In 3 trials players ingested a placebo (T I), a CAF (T II) or a CHO (T III) drink during court changeover. Total intake consisted of 2.81 of fluid, supplemented with 243 g CHO or with 364 mg CAF, respectively. Self-perceived "drive/motivation" and post-exercise hitting accuracy were evaluated. Plasma free fatty acids increments were lower after CHO while CAF administration had no effect. In all trials, plasma branched-chain amino acids (BCAA) concentrations decreased as a result of exercise; however, no differences were observed between trials. Plasma free tryptophan (TRP) to BCAA ratio was augmented in T I and T II while no change from basal level was found in T III. Plasma prolactin (PRL) and growth hormone (HGH) concentrations after cessation of exercise were lower in T III compared with T I and T II. No main effect for treatment was found for plasma ACTH, COR and beta-endorphin. Neither supplement affected number of won games. We conclude that CAF ingestion did not affect the plasma large neutral amino acids concentrations, neuroendocrine system responses or tennis performance. Lower plasma free TRP/BCAA ratio induced by CHO occurred concomitant with reduced plasma PRL and HGH concentrations, suggesting that the brain monoaminergic system might be affected if CHO-containing drinks are consumed during tennis match play. However, the data do not point towards an ergogenic value of reduced plasma free TRP/BCAA ratio. PMID- 27406550 TI - Chronic Diazepam Administration Failed to Induce Tolerance and Withdrawal Syndrome in Perinatally Undernourished Female Rats as Measured in the Open Field Drink Test. AB - Adult female rats, receiving a low protein diet at perinatal age and then recovered with balanced chow (D rats), were evaluated in the Open Field Drink Test (OFDT), after different acute and chronic treatments with benzodiazepines (BZD) ligands, as compared with control (C) female rats. Control and D rats showed similar reactivity to acute administration of diazepam (DZP, 1 mg/kg) and FG 7142 (2.5mg/kg), both BZD ligands with anxiolytic and anxiogenic effects, respectively. After chronic DZP treatment (3mg/kg/day i.p. for 3 weeks), C rats developed tolerance to the anxiolytic effect of DZP as well as withdrawal syndrome upon abrupt interruption of chronic treatment. On the contrary, D animals failed to develop tolerance to the anxiolytic effect of DZP, and did not show an increased anxiety upon withdrawal. The functionality of the GABAA receptor-complex, as measured by (36)Cl(-) uptake in cortical cerebral microsacs, was not altered in the DZP withdrawn rats. The lack of tolerance and withdrawal syndrome may be related to the incapacity of D rats to generate adaptive changes after chronic treatments. For instance, C rats showed a lower anxiety level in the OFDT after chronic vehicle administration, whereas D animals did not evidence such an adaptive response. Furthermore, D rats failed to respond to the anxiolytic effect of DZP after chronic vehicle treatment. These results reassert the deleterious effects of perinatal undernutrition on the capacity to develop adaptive responses to repeated drug administration or adequate stimuli. PMID- 27406551 TI - Effects of Early Concurrent Protein Malnutrition and Environmental Stimulation on the Central Nervous System and Behavior. AB - A complex program of environmental and sensory stimulation was developed to study its potential effects in reversing some of the alterations produced by early protein malnutrition in the brain and behavior of rats. Litters (dam plus 6 male pups) were fed diets containing 8% (malnourished) or 25% (well-nourished) casein. After weaning, the animals were maintained on the same diets as their respective dams until 50 days of age. Environmental stimulation consisted of 3-min daily handling from birth to 50 days of age. Additional stimulation was provided from birth to 50 days of age by rearing the rats in an enriched living cage and exposing the animals to visual, auditory and olfactory stimuli. At 50 days of age the animals were submitted to locomotor and inhibitory avoidance tests. Animals of the same age were sacrificed, the brain removed and divided in telencephalon, brain steam and cerebellum. DNA and RNA were assessed in telencephalon and cerebellum. Protein malnutrition produced brain weight deficits that were partially reversed by environmental stimulation. DNA and RNA levels were reduced by protein malnutrition and increased by environmental stimulation. The behavioral measures showed lower locomotor activity and higher latencies in inhibitory avoidance for malnourished animals as compared to well-nourished animals. Environmental stimulation reduced the aversiveness in the inhibitory avoidance test as showed by lower latencies in the stimulated group of animals. These results suggest that early protein malnutrition impairs brain and behavior of rats and that a complex program of environmental stimulation is beneficial to reverse some of those impairments. PMID- 27406552 TI - Differential Regional Distribution of Enterostatin, an Appetite Inhibiting Peptide, in the Brains of Zucker and Sprague-Dawley Rats. AB - Enterostatins are pentapeptides represented at the amino-terminus of procolipase molecule. Val-Pro-Asp-Pro-Arg or VPDPR is one such enterostatin. Pharmacologic studies suggest a role for VPDPR in appetite regulation and insulin secretion; however, due to the lack of a suitable assay method, the function of endogenous peptide has not been possible to discern until now. In the present investigation, we have shown the presence of a VPDPR-like immunoreactivity (VPDPR-LI) in the rat brain. On further characterization, brain VPDPR-LI was shown not to be due to APGPR, VPGPR, or VPDPR but to another peptide with an epitope similar to VPDPR. We have also examined the distribution of VPDPR-LI in different regions of the brains of Sprague-Dawley and Zucker rats. The results show (a) an uneven distribution of VPDPR-LI with the highest concentration in the striatum of both strains of rats, and (b) significantly lower levels of VPDPR-LI in all brain regions of Zucker compared to Sprague-Dawley rats. PMID- 27406553 TI - Scalable Synthesis of Few-Layer MoS2 Incorporated into Hierarchical Porous Carbon Nanosheets for High-Performance Li- and Na-Ion Battery Anodes. AB - It is still a challenging task to develop a facile and scalable process to synthesize porous hybrid materials with high electrochemical performance. Herein, a scalable strategy is developed for the synthesis of few-layer MoS2 incorporated into hierarchical porous carbon (MHPC) nanosheet composites as anode materials for both Li- (LIB) and Na-ion battery (SIB). An inexpensive oleylamine (OA) is introduced to not only serve as a hinder the stacking of MoS2 nanosheets but also to provide a conductive carbon, allowing large scale production. In addition, a SiO2 template is adopted to direct the growth of both carbon and MoS2 nanosheets, resulting in the formation of hierarchical porous structures with interconnected networks. Due to these unique features, the as-obtained MHPC shows substantial reversible capacity and very long cycling performance when used as an anode material for LIBs and SIBs, even at high current density. Indeed, this material delivers reversible capacities of 732 and 280 mA h g(-1) after 300 cycles at 1 A g(-1) in LIBs and SIBs, respectively. The results suggest that these MHPC composites also have tremendous potential for applications in other fields. PMID- 27406554 TI - Hysteresis of the magnetic properties of soft magnetic gels. AB - We present results of an experimental and theoretical study of the magnetic properties of soft magnetic gels consisting of micron-sized magnetizable particles embedded in a polymer matrix. Experiments demonstrate hysteretic dependences of composite magnetization on an applied magnetic field and non monotonic, with maximum, dependence of the sample susceptibilities on the field. We propose a theoretical approach which describes the main physical features of these experimental results. PMID- 27406555 TI - Delayed surgical repair of cranial burst fracture without strict dura closure: a prudent choice in selected patients? AB - OBJECTIVES: Surgical management of cranial burst fracture (CBF) usually involves craniotomy to remove the devitalized brain tissues, followed by watertight repair of dural tears. However, there were times when the dural tear was so extensive that a substantially large bone flap would have to be removed in order to expose the retracted dural margins before it could be repaired. In such cases, strict dural repair would incur a significantly higher risk of damages to the surrounding neural tissues and severe bleeding, especially when the fracture was in the vicinity of eloquent cortical areas and sinus. Basing on our own clinical experiences, we suggest strict dural closure is not mandatory for these selected patients. METHODS: A retrospective review of patients who underwent cranial surgery for CBF at our hospital was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were performed to evaluate the extent of dural and brain laceration and the existence of extra-cranial cerebral tissues. Routine craniotomy was delivered to remove the lacerated brain tissues and evacuate the hematoma. The dural defect was only partially fixed with patient's own tissues or artificial dura patch. Then the fractured bone flaps were restored using titanium micro plates and screws. Data including preoperative neurological status, surgery related complications, postoperative cranial fracture healing, and clinical outcomes were obtained through clinical and radiological examinations. RESULTS: From October 2004 to March 2013, a total of four patients diagnosed with CBF were treated by this dural closure sparing technique. Their average age was 18.4 months old and the average area of the skull defects was 91 cm(2), with an average interval between primary injury and surgery of 13 days. The diagnosis of CBF was confirmed by intraoperative findings like extrusion of cerebral tissues out of the lacerated dura mater and skull defects. The postoperative courses were uneventful and all patients' neurological functions improved after surgery. Postoperative three dimensional CT reconstruction of the cranial vault showed the skull fractures healed properly in all patients. No patient developed posttraumatic cerebrospinal fluid leak or epilepsy during the on average 24-month follow-up period. CONCLUSIONS: In those selected cases of CBF in whom an extraordinary large craniotomy would be required to expose the entire retracted dura margins, given satisfactory evacuation of devitalized brain tissues and restoration of the bone flaps were achieved, we suggest strict dura closure is not compulsory. PMID- 27406556 TI - Arachnoid cyst: a further anomaly associated with Kallmann syndrome? PMID- 27406557 TI - Apparent diffusion coefficient mapping in medulloblastoma predicts non infiltrative surgical planes. AB - INTRODUCTION: An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery. METHODS: Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles. RESULTS: Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 +/- 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %. CONCLUSIONS: ADC maps are valuable in predicting the infiltrative and non infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma. PMID- 27406558 TI - Traumatic cervical internal carotid artery pseudoaneurysm in a child refractory to initial endovascular treatment: case report and technical considerations. AB - PURPOSE: Optimal management of extracranial carotid artery dissections (eCAD) in pediatric patients is not well documented, and endovascular interventions are rarely reported. METHODS: A 10-year-old girl sustained multiple systemic injuries in a motor vehicle accident, including an eCAD with pseudoaneurysm. She initially failed both aspirin and endovascular stenting with progressive enlargement of a traumatic cervical carotid pseudoaneurysm and stenosis. RESULTS: Second-stage endovascular stent placement with coiling resulted in successful occlusion of the pseudoaneurysm. At 30-month imaging follow-up, the parent vessel remained patent with no evidence of the pseudoaneurysm. CONCLUSION: In the setting of poly trauma, management of eCAD can be complex especially in the pediatric population. There is little data on the endovascular treatment of eCAD in children. Failed endovascular therapies are extremely rare. Our report supports surveillance imaging as repeat endovascular treatment may be necessary. PMID- 27406559 TI - Salmonella Effectors SseF and SseG Interact with Mammalian Protein ACBD3 (GCP60) To Anchor Salmonella-Containing Vacuoles at the Golgi Network. AB - Following infection of mammalian cells, Salmonella enterica serovar Typhimurium (S Typhimurium) replicates within membrane-bound compartments known as Salmonella containing vacuoles (SCVs). The Salmonella pathogenicity island 2 type III secretion system (SPI-2 T3SS) translocates approximately 30 different effectors across the vacuolar membrane. SseF and SseG are two such effectors that are required for SCVs to localize close to the Golgi network in infected epithelial cells. In a yeast two-hybrid assay, SseG and an N-terminal variant of SseF interacted directly with mammalian ACBD3, a multifunctional cytosolic Golgi network-associated protein. Knockdown of ACBD3 by small interfering RNA (siRNA) reduced epithelial cell Golgi network association of wild-type bacteria, phenocopying the effect of null mutations of sseG or sseF Binding of SseF to ACBD3 in infected cells required the presence of SseG. A single-amino-acid mutant of SseG and a double-amino-acid mutant of SseF were obtained that did not interact with ACBD3 in Saccharomyces cerevisiae When either of these was produced together with the corresponding wild-type effector by Salmonella in infected cells, they enabled SCV-Golgi network association and interacted with ACBD3. However, these properties were lost and bacteria displayed an intracellular replication defect when cells were infected with Salmonella carrying both mutant genes. Knockdown of ACBD3 resulted in a replication defect of wild-type bacteria but did not further attenuate the growth defect of a DeltasseFG mutant strain. We propose a model in which interaction between SseF and SseG enables both proteins to bind ACBD3, thereby anchoring SCVs at the Golgi network and facilitating bacterial replication. IMPORTANCE: Upon invasion of epithelial cells, the majority of vacuoles containing Salmonella enterica migrate to the perinuclear region-located Golgi network and remain in this region of the cell during the first few rounds of bacterial replication, forming a clustered microcolony of vacuoles. This process requires the action of SseF and SseG, two effector proteins that are translocated by the Salmonella SPI-2 type III secretion system. However, little is known about how they function. Here, we show that both proteins interact with the mammalian Golgi network-associated protein ACBD3. To our knowledge, the SseF-SseG-ACBD3 interaction is the first example of a tethering complex between a pathogen-containing vacuole and a host cell organelle. PMID- 27406560 TI - Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection. AB - Anti-tumor necrosis factor alpha (anti-TNF-alpha) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-alpha signaling results in the development of nonprotective immunity against C. neoformans We found that transient depletion of TNF-alpha inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-alpha-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-alpha depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4(+) T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-alpha-depleted mice. Taken together, our results indicate that early TNF-alpha signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF alpha may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. IMPORTANCE: Increased susceptibility to invasive fungal infections in patients on anti-TNF-alpha therapies underlines the need for understanding the cellular effects of TNF-alpha signaling in promoting protective immunity to fungal pathogens. Here, we demonstrate that early TNF-alpha signaling is required for classical activation and accumulation of DC in LALN of C. neoformans-infected mice. Subsequent transcriptional initiation of Th17 followed by Th1 programming in LALN results in pulmonary accumulation of gamma interferon- and interleukin-17A-producing T cells and effective fungal clearance. All of these crucial steps are severely impaired in mice that undergo anti-TNF-alpha treatment, consistent with their inability to clear C. neoformans This study identified critical interactions between cells of the innate immune system (DC), the emerging T cell responses, and cytokine networks with a central role for TNF alpha which orchestrate the development of the immune protection against cryptococcal infection. This information will be important in aiding development and understanding the potential side effects of immunotherapies. PMID- 27406561 TI - Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins. AB - The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy-based on the construction of a lectin glycan interaction (LGI) network-to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity. IMPORTANCE: Microbial pathogens may express a wide range of carbohydrate-specific adhesion proteins that mediate adherence to host tissues. Pathogen attachment to host cells is achieved through the binding of these lectin-like adhesins to glycans on human glycoproteins. In only a few cases have the human receptors of pathogenic adhesins been described. We developed a new strategy to predict these interacting receptors. Therefore, we developed a novel LGI network that would allow the mapping of potential adhesin binding receptors in the host with prioritization, based on the experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins (bacterial uroepithelial FimH from E. coli and fungal Epa and Als adhesins from C. glabrata and C. albicans) were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with human-pathogenic viruses and to discover whether FimH adhesin has anti-HIV activity. PMID- 27406562 TI - Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum-Infected Erythrocytes to Endothelial Cells. AB - Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLbeta domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-alpha)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-alpha activated primary brain and lung endothelial cells. IMPORTANCE: Cerebral malaria is a severe neurological complication of P. falciparum infection associated with infected erythrocyte (IE) binding in cerebral vessels. Yet little is known about the mechanisms by which parasites adhere in the brain or other microvascular sites. Here, we studied parasite lines expressing group A DC13-containing PfEMP1 variants, a subset that has previously been shown to have high brain cell- and other endothelial cell-binding activities. We show that DC13-containing PfEMP1 variants have dual EPCR- and ICAM-1-binding activities and that both receptors are involved in parasite adherence to lung and brain endothelial cells. As both EPCR and ICAM-1 are implicated in cerebral malaria, these findings suggest the possibility that parasites with dual binding activities are involved in parasite sequestration to microvascular beds with low CD36 expression, such as the brain, and we urge more research into the multiadhesive properties of PfEMP1 variants. PMID- 27406563 TI - CtaM Is Required for Menaquinol Oxidase aa3 Function in Staphylococcus aureus. AB - Staphylococcus aureus is the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability of S. aureus to cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (o type, bd type, and aa3 type), the genome contains genes encoding only two respiratory oxygen reductases, cydAB and qoxABCD Previous investigation showed that cydAB and qoxABCD are required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of the cydAB and qoxABCD in virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is an aa3-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as a bo3-type menaquinol oxidase. However, the bo3 form of QoxABCD restricts the carbon sources that can support the growth of S. aureus In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiring Firmicutes In total, these studies establish the heme A biosynthesis pathway in S. aureus, determine that QoxABCD is a type aa3 menaquinol oxidase, and reveal CtaM as a new protein required for type aa3 menaquinol oxidase function in multiple bacterial genera. IMPORTANCE: Staphylococcus aureus relies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of the S. aureus electron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain of S. aureus is comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration. PMID- 27406564 TI - Metabolic Regulation as a Consequence of Anaerobic 5-Methylthioadenosine Recycling in Rhodospirillum rubrum. AB - Rhodospirillum rubrum possesses a novel oxygen-independent, aerobic methionine salvage pathway (MSP) for recycling methionine from 5-methylthioadenosine (MTA), the MTA-isoprenoid shunt. This organism can also metabolize MTA as a sulfur source under anaerobic conditions, suggesting that the MTA-isoprenoid shunt may also function anaerobically as well. In this study, deep proteomics profiling, directed metabolite analysis, and reverse transcriptase quantitative PCR (RT qPCR) revealed metabolic changes in response to anaerobic growth on MTA versus sulfate as sole sulfur source. The abundance of protein levels associated with methionine transport, cell motility, and chemotaxis increased in the presence of MTA over that in the presence of sulfate. Purine salvage from MTA resulted primarily in hypoxanthine accumulation and a decrease in protein levels involved in GMP-to-AMP conversion to balance purine pools. Acyl coenzyme A (acyl-CoA) metabolic protein levels for lipid metabolism were lower in abundance, whereas poly-beta-hydroxybutyrate synthesis and storage were increased nearly 10-fold. The known R. rubrum aerobic MSP was also shown to be upregulated, to function anaerobically, and to recycle MTA. This suggested that other organisms with gene homologues for the MTA-isoprenoid shunt may also possess a functioning anaerobic MSP. In support of our previous findings that ribulose-1,5-carboxylase/oxygenase (RubisCO) is required for an apparently purely anaerobic MSP, RubisCO transcript and protein levels both increased in abundance by over 10-fold in cells grown anaerobically on MTA over those in cells grown on sulfate, resulting in increased intracellular RubisCO activity. These results reveal for the first time global metabolic responses as a consequence of anaerobic MTA metabolism compared to using sulfate as the sulfur source. IMPORTANCE: In nearly all organisms, sulfur containing byproducts result from many metabolic reactions. Unless these compounds are further metabolized, valuable organic sulfur is lost and can become limiting. To regenerate the sulfur-containing amino acid methionine, organisms typically employ one of several variations of a "universal" methionine salvage pathway (MSP). A common aspect of the universal MSP is a final oxygenation step. This work establishes that the metabolically versatile bacterium Rhodospirillum rubrum employs a novel MSP that does not require oxygen under either aerobic or anaerobic conditions. There is also a separate, dedicated anaerobic MTA metabolic route in R. rubrum This work reveals global changes in cellular metabolism in response to anaerobic MTA metabolism compared to using sulfate as a sulfur source. We found that cell mobility and transport were enhanced, along with lipid, nucleotide, and carbohydrate metabolism, when cells were grown in the presence of MTA. PMID- 27406565 TI - Transfer of DNA from Bacteria to Eukaryotes. AB - Historically, the members of the Agrobacterium genus have been considered the only bacterial species naturally able to transfer and integrate DNA into the genomes of their eukaryotic hosts. Yet, increasing evidence suggests that this ability to genetically transform eukaryotic host cells might be more widespread in the bacterial world. Indeed, analyses of accumulating genomic data reveal cases of horizontal gene transfer from bacteria to eukaryotes and suggest that it represents a significant force in adaptive evolution of eukaryotic species. Specifically, recent reports indicate that bacteria other than Agrobacterium, such as Bartonella henselae (a zoonotic pathogen), Rhizobium etli (a plant symbiotic bacterium related to Agrobacterium), or even Escherichia coli, have the ability to genetically transform their host cells under laboratory conditions. This DNA transfer relies on type IV secretion systems (T4SSs), the molecular machines that transport macromolecules during conjugative plasmid transfer and also during transport of proteins and/or DNA to the eukaryotic recipient cells. In this review article, we explore the extent of possible transfer of genetic information from bacteria to eukaryotic cells as well as the evolutionary implications and potential applications of this transfer. PMID- 27406566 TI - Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles. AB - Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast (Saccharomyces cerevisiae) are epigenetic elements of inheritance that induce phenotypic changes of their host cells. The prototype yeast prion is the translation termination factor Sup35. Prions composed of Sup35 or its modular prion domain NM are heritable and are transmitted vertically to progeny or horizontally during mating. Interestingly, in mammalian cells, protein aggregates derived from yeast Sup35 NM behave as true infectious entities that employ dissemination strategies similar to those of mammalian prions. While transmission is most efficient when cells are in direct contact, we demonstrate here that cytosolic Sup35 NM prions are also released into the extracellular space in association with nanometer-sized membrane vesicles. Importantly, extracellular vesicles are biologically active and are taken up by recipient cells, where they induce self-sustained Sup35 NM protein aggregation. Thus, in mammalian cells, extracellular vesicles can serve as dissemination vehicles for protein-based epigenetic information transfer. IMPORTANCE: Prions are proteinaceous infectious particles that propagate by templating their quaternary structure onto nascent proteins of the same kind. Prions in yeast act as heritable epigenetic elements that can alter the phenotype when transmitted to daughter cells or during mating. Prion activity is conferred by so-called prion domains often enriched in glutamine and asparagine residues. Interestingly, many mammalian proteins also contain domains with compositional similarity to yeast prion domains. We have recently provided a proof-of-principle demonstration that a yeast prion domain also retains its prion activity in mammalian cells. We demonstrate here that cytosolic prions composed of a yeast prion domain are also packaged into extracellular vesicles that transmit the prion phenotype to bystander cells. Thus, proteins with prion-like domains can behave as proteinaceous information molecules that exploit the cellular vesicle trafficking machinery for intercellular long-distance dissemination. PMID- 27406567 TI - LPS Remodeling Triggers Formation of Outer Membrane Vesicles in Salmonella. AB - Outer membrane vesicles (OMV) are proposed to mediate multiple functions during pathogenesis and symbiosis. However, the mechanisms responsible for OMV formation remain poorly understood. It has been shown in eukaryotic membranes that lipids with an inverted-cone shape favor the formation of positive membrane curvatures. Based on these studies, we formulated the hypothesis that lipid A deacylation might impose shape modifications that result in the curvature of the outer membrane (OM) and subsequent OMV formation. We tested the effect of lipid A remodeling on OMV biogenesis employing Salmonella enterica serovar Typhimurium as a model organism. Expression of the lipid A deacylase PagL resulted in increased vesiculation, without inducing an envelope stress response. Mass spectrometry analysis revealed profound differences in the patterns of lipid A in OM and OMV, with accumulation of deacylated lipid A forms exclusively in OMV. OMV biogenesis by intracellular bacteria upon macrophage infection was drastically reduced in a pagL mutant strain. We propose a novel mechanism for OMV biogenesis requiring lipid A deacylation in the context of a multifactorial process that involves the orchestrated remodeling of the outer membrane. IMPORTANCE: The role of lipid remodeling in vesiculation is well documented in eukaryotes. Similarly, bacteria produce membrane-derived vesicles; however, the molecular mechanisms underlying their production are yet to be determined. In this work, we investigated the role of outer membrane remodeling in OMV biogenesis in S Typhimurium. We showed that the expression of the lipid A deacylase PagL results in overvesiculation with deacylated lipid A accumulation exclusively in OMV. An S Typhimurium DeltapagL strain showed a significant reduction in intracellular OMV secretion relative to the wild-type strain. Our results suggest a novel mechanism for OMV biogenesis that involves outer membrane remodeling through lipid A modification. Understanding how OMV are produced by bacteria is important to advance our understanding of the host-pathogen interactions. PMID- 27406570 TI - Discussion of "Computational Electrocardiography: Revisiting Holter ECG Monitoring". AB - This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Computational Electrocardiography: Revisiting Holter ECG Monitoring" written by Thomas M. Deserno and Nikolaus Marx. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Deserno and Marx. In subsequent issues the discussion can continue through letters to the editor. PMID- 27406569 TI - Erratum for Smith et al., Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells. PMID- 27406568 TI - The Role of Lipid Competition for Endosymbiont-Mediated Protection against Parasitoid Wasps in Drosophila. AB - Insects commonly harbor facultative bacterial endosymbionts, such as Wolbachia and Spiroplasma species, that are vertically transmitted from mothers to their offspring. These endosymbiontic bacteria increase their propagation by manipulating host reproduction or by protecting their hosts against natural enemies. While an increasing number of studies have reported endosymbiont mediated protection, little is known about the mechanisms underlying this protection. Here, we analyze the mechanisms underlying protection from parasitoid wasps in Drosophila melanogaster mediated by its facultative endosymbiont Spiroplasma poulsonii Our results indicate that S. poulsonii exerts protection against two distantly related wasp species, Leptopilina boulardi and Asobara tabida S. poulsonii-mediated protection against parasitoid wasps takes place at the pupal stage and is not associated with an increased cellular immune response. In this work, we provide three important observations that support the notion that S. poulsonii bacteria and wasp larvae compete for host lipids and that this competition underlies symbiont-mediated protection. First, lipid quantification shows that both S. poulsonii and parasitoid wasps deplete D. melanogaster hemolymph lipids. Second, the depletion of hemolymphatic lipids using the Lpp RNA interference (Lpp RNAi) construct reduces wasp success in larvae that are not infected with S. poulsonii and blocks S. poulsonii growth. Third, we show that the growth of S. poulsonii bacteria is not affected by the presence of the wasps, indicating that when S. poulsonii is present, larval wasps will develop in a lipid-depleted environment. We propose that competition for host lipids may be relevant to endosymbiont-mediated protection in other systems and could explain the broad spectrum of protection provided. IMPORTANCE: Virtually all insects, including crop pests and disease vectors, harbor facultative bacterial endosymbionts. They are vertically transmitted from mothers to their offspring, and some protect their host against pathogens. Here, we studied the mechanism of protection against parasitoid wasps mediated by the Drosophila melanogaster endosymbiont Spiroplasma poulsonii Using genetic manipulation of the host, we provide strong evidence supporting the hypothesis that competition for host lipids underlies S. poulsonii-mediated protection against parasitoid wasps. We propose that lipid competition-based protection may not be restricted to Spiroplasma bacteria but could also apply other endosymbionts, notably Wolbachia bacteria, which can suppress human disease-causing viruses in insect hosts. PMID- 27406571 TI - Evaluation of phytic acid utilization by S. cerevisiae strains used in fermentation processes and biomass production. AB - Saccharomyces cerevisiae is a well-studied yeast species used mainly in fermentation processes, bakery, and for SCP (Single Cell Protein) acquisition. The aim of the study was to analyze the possibility of phytic acid utilization as one of the hydrolysis processes carried out by yeast. The analysis of 30 yeast strains used in fermentation and for biomass production, that were grown in media containing phytic acid, revealed a high variability in the biomass production rate and the capability to hydrolyze phytates. No correlation between a high biomass concentration and a high level of phytate hydrolysis was found. Only four analyzed strains (Bayanus IOC Efficience, Sano, PINK EXCEL, FINAROME) were able to reduce the phytic acid concentration by more than 33.5%, from the initial concentration 103.0 +/- 2.1 MUg/ml to the level below 70 MUg/ml. The presented results suggest that the selected wine and fodder yeast can be used as in situ source of phosphohydrolases in fermentation processes, and especially in the production of fodder proteins. However, further studies aimed at the optimization of growing parameters, such as the maximization of phytase secretion, and a comprehensive analysis of the catalytic activity of the isolated phosphohydrolases, are necessary. PMID- 27406572 TI - Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001 2011: A case series and literature review. AB - BACKGROUND: Mycobacterium scrofulaceum is a well-known pathogen associated with cervical lymphadenitis in children. However, pulmonary M. scrofulaceum disease is a rare condition with unknown clinical features. The present study aimed to clarify the clinical features of pulmonary M. scrofulaceum disease described in recent cases and reports. METHODS: We reviewed the medical records of all adult patients with pulmonary M. scrofulaceum disease at Keio University Hospital and the National Center for Global Health and Medicine Center Hospital between 2001 and 2011. We also conducted a review of the PubMed database to identify additional cases of pulmonary M. scrofulaceum disease in adults. RESULTS: Our study identified 8 cases of pulmonary M. scrofulaceum disease at the 2 identified institutions during our study period. Most cases were diagnosed in middle-aged and elderly men with underlying pulmonary diseases such as chronic obstructive pulmonary disease and Mycobacterium avium complex lung disease, as well as those with a history of pulmonary tuberculosis. In contrast, most previously reported cases identified through our literature review had a history of dust inhalation or underlying silicosis. Three of 8 cases at our institutions and 20 of 23 cases from the literature were treated with combination therapies. CONCLUSIONS: We conclude that in the recent histories of our institutions, pulmonary M. scrofulaceum disease has mainly occurred in patients with chronic pulmonary diseases. We further conclude that combination therapies that include clarithromycin might yield better patient outcomes. PMID- 27406574 TI - Positive exercise test? PMID- 27406573 TI - Cloning and expression of a 16-kDa recombinant protein from Angiostrongylus cantonensis for use in immunoblot diagnosis of human angiostrongyliasis. AB - Angistrongylus cantonensis is a zoonotic nematode parasite and causative agent of human angiostrongyliasis, which clinically presents as eosinophilic meningitis or meningoencephalitis. Diagnosis of the disease is problematic since parasitologic findings are infrequent, and infection determinations must be based on the clinical symptoms and serological tests with limited specificities and sensitivities. The aim of the present study was to identify and generate a novel recombinant protein from A. cantonensis and evaluate its efficacy in the diagnosis of human angiostrongyliasis when incorporated into a Western blot serodiagnostic system. A cDNA protein expression library from adult A. cantonensis was constructed, followed by immunoscreening with serum from confirmed infected patients to identify and isolate immunoreactive clones. One clone, designated fAC40, possessed a partial sequence encoding a LisH protein domain with a predicted molecular weight of 16 kDa and containing four predicted antigenic peptides. By incorporating recombinant fAC40 in Western immunoblot tests using a serum panel consisting of confirmed and clinically diagnosed cases of human angiostrongyliasis and other helminthic infections, fAC40 exhibited a sensitivity and specificity of 91.8 and 100 %, respectively, and a positive and negative predictive value of 100 and 97.19 %, respectively, in the diagnosis of angiostrongyliasis. Importantly, it was not reactive with antibodies from serum of patients infected with Gnathostoma spinigerum and Cysticercus cellulosae, infections that clinically present neurological symptoms similar to angiostrongyliasis. These data demonstrate that the 16-kDa recombinant protein from A. cantonensis possesses high potential as a candidate antigen for a more sensitive and specific serodiagnosis of human angiostrongyliasis. PMID- 27406575 TI - Hemiplegic migraine and late-onset photosensitive epileptic seizures. PMID- 27406576 TI - Regular endurance training in adolescents impacts atrial and ventricular size and function. AB - Aims: The aims of the study were to explore the effects of long-term endurance exercise on atrial and ventricular size and function in adolescents and to examine whether these changes are related to maximal oxygen uptake (VO2max). Methods and results: Twenty-seven long-term endurance-trained adolescents aged 13 19 years were individually matched by age and gender with 27 controls. All participants, 22 girls and 32 boys, underwent an echocardiographic examination at rest, including standard and colour tissue Doppler investigation. VO2max was assessed during treadmill exercise. All heart dimensions indexed for body size were larger in the physically active group compared with controls: left ventricular end-diastolic volume 60 vs. 50 mL/m2 (P <0.001), left atrial volume 27 vs. 19 mL/m2 (P < 0.001), and right ventricular (RV) and right atrial area 15 vs. 13 and 9 vs. 7 cm2/m2, respectively (P <0.001 for both). There were strong associations between the size of the cardiac chambers and VO2max. Further, we found improved systolic function in the active group compared with controls: left ventricular ejection fraction 61 vs. 59% (P= 0.036), tricuspid annular plane systolic excursion 12 vs. 10 mm/m2 (P= 0.008), and RV early peak systolic velocity s' 11 vs. 10 cm/s (P = 0.031). Conclusion: Cardiac remodelling to long term endurance exercise in adolescents is manifested by an increase in atrial as well as ventricular dimensions. The physically active group also demonstrated functional remodelling with an increase in TAPSE and systolic RV wall velocity. These findings have practical implications when assessing cardiac enlargement and function in physically active youngsters. PMID- 27406577 TI - Nocebo effect of informed consent: circulatory collapse before elective caesarean section. PMID- 27406579 TI - Interventional radiology for abnormally invasive placenta: do we need an alternative? PMID- 27406578 TI - Maternal sedation during scheduled versus unscheduled cesarean delivery: implications for skin-to-skin contact. AB - BACKGROUND: Early maternal skin-to-skin contact confers numerous benefits to the newborn, but maternal sedation during cesarean delivery could have safety implications for early skin-to-skin contact in the operating room. We compared patient-reported and observer-assessed levels of sedation during unscheduled and scheduled cesarean deliveries. METHODS: Laboring women undergoing unscheduled cesarean delivery with epidural anesthesia, and scheduled cesarean delivery with spinal anesthesia were enrolled. Sedation levels, measured using patient-reported (1=least sedated to 10=most sedated) and observer-assessed (0=most sedated to 5=least sedated) scales, were evaluated at baseline and 15, 30, 45, and 60min following a T4 sensory level. The primary outcomes were patient-reported sedation at 45min and the areas under the sedation curves. RESULTS: Patient-reported levels of sedation were greater at 45min in laboring women undergoing unscheduled (median 7.5, IQR 5-9) versus scheduled cesarean delivery (median 4, IQR 3-6) (difference in medians 3.5, 99% CI 0 to 5). Observer-assessed sedation was not different between groups. The area under the time curve for patient-reported sedation was greater in the unscheduled group, median difference 162 score min (95% CI 52 to 255). The area under the time curve for observer-assessed sedation was greater in the unscheduled group, median difference 26 score min (99% CI 0 to 41). Times to skin-to-skin contact and breastfeeding were not different. CONCLUSIONS: Women undergoing unscheduled cesarean deliveries are more sedated than women undergoing scheduled cesarean deliveries. Skin-to-skin protocols for cesarean deliveries must consider maternal sedation and anesthesiologists should use sedating medications judiciously. PMID- 27406580 TI - Anesthetic management of a parturient with varicella presenting for cesarean delivery. AB - Varicella (chicken pox) infection is associated with a significant risk of maternal and fetal morbidity and mortality. The choice of anesthetic technique, either neuraxial or general anesthesia, in such patients remains controversial. Anesthetic management depends not only on the extent of disease involvement and associated complications, but also on the indication for cesarean delivery. We present the anesthetic management of a 25-year-old parturient with acute varicella infection who underwent emergency cesarean delivery under spinal anesthesia. The risks and benefits of neuraxial anesthesia in the setting of varicella are discussed. PMID- 27406581 TI - Molecular characterization, expression and methylation status analysis of BMP4 gene in skin tissue of Liaoning cashmere goat during hair follicle cycle. AB - Bone morphogenetic protein 4 (BMP4) is a member of the bone morphogenetic protein family (BMPs). It is involved in the development and cycle of hair follicle, as well as, is thought to be a potential candidate gene for cashmere traits in goats. In the present study, we isolated and characterized a full-length open reading frame (ORF) of BMP4 cDNA from the skin tissue of Liaoning cashmere goat, and investigated the transcriptional pattern and methylation status of BMP4 gene in skin tissue of this breed during different stages of hair follicle cycle. The sequence analysis indicated that the isolated cDNA was 1264-bp in length containing a complete ORF of 1230-bp. It encoded a precursor peptide of 409 amino acids with a signal peptide of 19 amino acids. The structural analysis indicated that goat BMP4 contains typical TGF-beta propeptide and TGF-beta domains. In skin tissue, BMP4 is generally transcribed in an ascendant pattern from anagen to telogen. The methylation level of 5' flanking regulatory region of BMP4 gene might be involved in its mRNA expression in skin tissue: a higher BMP4 methylation level in skin coincides with a lower expression of BMP4 mRNA. These results from the present work provided a foundation for further insight into the functional and regulatory characteristics of BMP4 in the development and cycle of hair follicle in Liaoning Cashmere goat. PMID- 27406583 TI - Three new acyltyramines from Anisodus luridus Link et Otto (Solanaceae). AB - Three new acyltyramines, N-[2-(4-hydroxyphenyl)ethyl]hentriacontanamide (1), N-[2 (4-hydroxyphenyl)ethyl]nonacosanamide (2) and N-[2-(4 hydroxyphenyl)ethyl]heneicosanamide (3) have been isolated from n-hexane extract of leaves of Anisodus luridus (Solanaceae). Successive extraction of defatted leaves of A. luridus with methanol afforded a residue on removal of solvent under reduced pressure. Residue was partitioned by means of chloroform and n-butanol. Chromatographic resolution of n-BuOH extract afforded six known compounds, apigenin (4), luteolin (5), quercetin (6), quercetin 3-O-alpha-l-rhamnoside (7), kaempferol 3-O-alpha-rhamnoside (8) and quercetin 3-O-alpha-l-rhamnopyranosyl-(1 >6)-beta-d-glucopyranoside (9). The structures of the isolated compounds were assigned with the help of spectroscopic techniques. This is the first report of isolation of these compounds from this plant. PMID- 27406582 TI - Genetic structuring in a relictual population of screaming hairy armadillo (Chaetophractus vellerosus) in Argentina revealed by a set of novel microsatellite loci. AB - The screaming hairy armadillo (Chaetophractus vellerosus) is a mammal species containing disjunct and isolated populations. In order to assess the effect of habitat fragmentation and geographic isolation, we developed seven new microsatellite loci isolated from low-coverage genome shotgun sequencing data for this species. Among these loci, six microsatellites were found to be polymorphic with 8-26 alleles per locus detected across 69 samples analyzed from a relictual population of the species located in the northeast of the Buenos Aires Province (Argentina). Mean allelic richness and polymorphic information content were 15 and 0.75, with observed and expected heterozygosities ranging from 0.40 to 0.67 and 0.58 to 0.90, respectively. All loci showed departures from Hardy-Weinberg equilibrium. The analysis of population structure in this relictual population revealed three groups of individuals that are genetically differentiated. These newly developed microsatellites will constitute a very useful tool for the estimation of genetic diversity and structure, population dynamics, social structure, parentage and mating system in this little-studied armadillo species. Such genetic data will be particularly helpful for the development of conservation strategies for this isolated population and also for the endangered Bolivian populations previously recognized as a distinct species (Chaetophractus nationi). PMID- 27406584 TI - Utility of MRI versus tumor markers for post-treatment surveillance of marker positive CNS germ cell tumors. AB - Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences. PMID- 27406585 TI - Age alone is not a predictor for survival in glioblastoma. AB - Over half of glioblastoma (GBM) cases are diagnosed in patients older than 65 years. Their median overall survival (OS) is 4-5 months, compared with 12-14 months in patients younger than 70 years. This retrospective audit aims to identify patterns of care and survival of patients diagnosed with GBM at a single institution in Melbourne, Australia. Consecutive histological diagnoses of adult primary GBM from January 2010 to December 2012 were retrospectively identified from medical records. Demographic, treatment and survival characteristics were recorded until death, with follow-up to January 1st 2015. Survival was estimated by Kaplan-Meier method. Planned, sub-group analyses were conducted using multivariate Cox proportional hazards model to identify differences between elderly and younger cohorts, as well as ECOG. 165 patients were identified (36 % aged >=70 years). Those >=70 years had a poorer performance status (ECOG 3-4: 27 vs 10 %, p = .005); poorer median OS (2.6 vs 11.5 months, p < .001); and were less likely to receive adjuvant treatment (no treatment: 40 vs 16 %, p < .001) compared with patients <70 years. Age was not a significant predictor of poorer os (HR 1.0; 0.99-1.03; p > .05), after adjusting for other clinical factors. Significant predictors of poorer os were poor performance status (p = .001), bilateral tumours (p = .04), biopsy only (p = .001), and no adjuvant treatment (p < .001). In patients diagnosed with GBM, those older than 70 years often present with poor performance status, are less likely to receive adjuvant treatment and have inferior os compared with younger patients. Treatment recommendations should be based on performance status/fitness, not age alone. PMID- 27406586 TI - The clinical significance of fascin expression in a newly diagnosed primary glioblastoma. AB - The actin-binding protein fascin has been associated with clinically aggressive tumors and poor prognosis. The purpose of this study was to investigate possibility of fascin expression as a prognostic factor in a newly diagnosed primary glioblastoma (GBM). Between July 2007 and December 2013, 37 out of 126 patients diagnosed with GBM satisfied the following inclusion criteria: (1) the presence of immunohistochemically-available tissue, (2) a new primary GBM, (3) gross-total resection, and (4) standardized adjuvant treatment, known as the Stupp regimen. The median follow-up period was 18 months (range 5-95). According to the staining intensity of fascin, progression-free survival (PFS) in the low intensity fascin group (median PFS 9.0 months; 95 % CI 6.0-12.0) was longer than PFS in the high-intensity fascin group (median PFS 7.0 months; 95 % CI 5.6-10.4; p = 0.024). Overall survival (OS) in the low-intensity fascin group (median OS 20.0 months; 95 % CI 17.7-22.4) was longer than OS in the high-intensity fascin group (median OS 13.0 months; 95 % CI 8.2-17.8; p = 0.031). And, the staining intensity of fascin was a statistically significant factor in PFS and OS according to univariate and multivariate analyses (univariate analysis p = 0.043 and p = 0.043; multivariate analysis p = 0.041 and p = 0.044). Our clinical study showed that fascin expression intensity may be correlated with clinical outcomes of a newly diagnosed primary GBM, especially with regard to PFS and OS. PMID- 27406587 TI - Application of brush cytology for FISH-based detection of 1p/19q codeletion in oligodendroglial tumors. AB - Currently, oligodendroglial tumours (OT) are routinely tested for 1p/19q codeletion, a genetic abnormality of prognostic value. This analysis is most commonly performed by fluorescence in situ hybridization (FISH) on formalin fixed, paraffin embedded (FFPE) tissue sections, which is time-consuming and often difficult to interpret, mainly due to the presence of truncated and overlapping nuclei. To overcome these methodological disadvantages, we investigated the validity of cytospins prepared from brushings of fresh tissue samples for assessing 1p/19q status by FISH. For this purpose, FISH analysis of 1p/19q codeletion was performed on FFPE tissue sections and cytospins prepared from brushing of corresponding fresh tissue in a series of 35 central nervous system tumours (16 OT and 19 non-OT). An aberrant 1p/19q status was found in 11/16 (69 %) OT samples and included codeletion of 1p/19q (7), 1p/19q imbalance (2) isolated 19q deletion (1) and 1p imbalance (1). None of the 19 non-OT samples showed 1p/19q codeletion. Results of FISH were concordant between FFPE sections and cytospins in all cases in which both types of slides gave interpretable results. Interpretation of FISH signals on cytospins was easier and quicker than on FFPE sections. Our study showed that cytospins prepared from brushing of fresh tissue samples allow quick and reliable FISH based analysis of 1p/19q status and can substitute traditional FFPE sections when fresh tissue is available. PMID- 27406588 TI - Mir-449a, a potential diagnostic biomarker for WNT group of medulloblastoma. AB - Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The 5 year disease-free survival rate is rather low. There is a consensus that MB can be divided into at least four clinically, transcriptionally, and genetically distinct molecular variants, being designated as wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4. It poses a great challenge to the design of therapeutic strategy for MB patients. Intensive clinical intervention, including high dose radiotherapy, is commonly used in treatment of high risk MB, most of which are considered to be Group 3 patients. But such intensive therapy should be avoided to protect neurologic function of patients in the lower risk WNT group. In present study, MB subgroup assignment in formalin-fixed paraffin embedded (FFPE) specimens from 45 Chinese patients were performed by Nanostring platform using 22 well-known signature genes. Based on comparative expression profiles of miRNA real-time PCR microarray in MB cells with and without treatment of demethylation reagent, as well as MSP assay, miR-449a was demonstrated to be significantly silenced by aberrant DNA methylation in tumor cells. Real-time PCR showed that expression level of miR-449a in WNT group was significantly different from other subgroups, although it was down-regulated in most of the MB samples. In conclusion, current study demonstrates for the first time the feasibility of using the Nanostring assay for subgrouping of MBs in Chinese patients. In addition, MiR-449a, a candidate tumor suppressor regulated by hypermethylation, is a novel potential diagnostic marker for WNT group of MBs. PMID- 27406590 TI - Public Health England advice on PSA testing. PMID- 27406589 TI - A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma. AB - Antiangiogenic therapy can rapidly reduce vascular permeability and cerebral edema but high doses of bevacizumab may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose bevacizumab in combination with lomustine (CCNU) compared to standard dose bevacizumab in patients with recurrent glioblastoma. Patients (N = 71) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 1:1 to receive bevacizumab monotherapy (10 mg/kg) or low dose bevacizumab (5 mg/kg) in combination with lomustine (90 mg/m(2)). The primary end point was progression-free survival (PFS) based on a blinded, independent radiographic assessment of post-contrast T1-weighted and non-contrast T2/FLAIR weighted magnetic resonance imaging (MRI) using RANO criteria. For 69 evaluable patients, median PFS was not significantly longer in the low dose bevacizumab + lomustine arm (4.34 months, CI 2.96-8.34) compared to the bevacizumab alone arm (4.11 months, CI 2.69-5.55, p = 0.19). In patients with first recurrence, there was a trend towards longer median PFS time in the low dose bevacizumab + lomustine arm (4.96 months, CI 4.17-13.44) compared to the bevacizumab alone arm (3.22 months CI 2.5-6.01, p = 0.08). The combination of low dose bevacizumab plus lomustine was not superior to standard dose bevacizumab in patients with recurrent glioblastoma. Although the study was not designed to exclusively evaluate patients at first recurrence, a strong trend towards improved PFS was seen in that subgroup for the combination of low dose bevacizumab plus lomustine. Further studies are needed to better identify such subgroups that may most benefit from the combination treatment. PMID- 27406591 TI - Flying with eight wings: inter-sex differences in wingbeat kinematics and aerodynamics during the copulatory flight of damselflies (Ischnura elegans). AB - Copulation in the blue-tailed damselfly, Ischnura elegans, can last over 5 hours, during which the pair may fly from place to place in the so-called "wheel position". We filmed copulatory free-flight and analyzed the wingbeat kinematics of males and females in order to understand the contribution of the two sexes to this cooperative flight form. Both sexes flapped their wings but at different flapping frequencies resulting in a lack of synchronization between the flapping of the two insects. Despite their unusual body posture, females flapped their wings in a stroke-plane not significantly different to that of the males (repeated-measures ANOVA, F1,7 = 0.154, p = 0.71). However, their flapping amplitudes were smaller by 42 +/- 17 %, compared to their male mates (t test, t 7 = 9.298, p < 0.001). This was mostly due to shortening of the amplitude at the ventral stroke reversal point. Compared to solitary flight, males flying in copula increased flapping frequency by 19 %, while females decreased flapping amplitude by 27 %. These findings suggest that although both sexes contribute to copulatory flight, females reduce their effort, while males increase their aerodynamic output in order to carry both their own weight and some of the female's weight. This increased investment by the male is amplified due to male I. elegans being typically smaller than females. The need by smaller males to fly while carrying some of the weight of their larger mates may pose a constraint on the ability of mating pairs to evade predators or counter interference from competing solitary males. PMID- 27406592 TI - Deep Intronic Sequence Variants in COL2A1 Affect the Alternative Splicing Efficiency of Exon 2, and May Confer a Risk for Rhegmatogenous Retinal Detachment. AB - COL2A1 mutations causing haploinsufficiency of type II collagen cause type 1 Stickler syndrome that has a high risk of retinal detachment and failure of the vitreous to develop normally. Exon 2 of COL2A1 is alternatively spliced, expressed in the eye but not in mature cartilage and encodes a region that binds growth factors TGFbeta1 and BMP-2. We investigated how both an apparently de novo variant and a polymorphism in intron 2 altered the efficiency of COL2A1 exon 2 splicing and how the latter may act as a predisposing risk factor for the occurrence of posterior vitreous detachment (PVD)-associated rhegmatogenous retinal detachment (RRD) in the general population. Using amplification of illegitimate transcripts and allele-specific minigenes expressed in cultured cells, we demonstrate variability in exon 2 inclusion not only between different control individuals, but also between different COL2A1 alleles. We identify transacting factors that bind to allele-specific RNA sequences, and investigate the effect of knockdown and overexpression of these factors on exon 2 splicing efficiency. Finally, using a specific cohort of patients with PVD-associated RRD and a control population, we demonstrate a significant difference in the frequency of the COL2A1 intronic variant rs1635532 between the two groups. PMID- 27406593 TI - Selection and Characterization of Bacillus thuringiensis (Berliner) (Eubacteriales: Bacillaceae) Strains for Ecdytolopha aurantiana (Lima) (Lepidoptera: Tortricidae) Control. AB - The citrus fruit borer, Ecdytolopha aurantiana (Lima, 1927) (Lepidoptera: Tortricidae), is responsible for major losses to the citrus industry because it causes rot and drop of fruits. The current study aimed to select and characterize Bacillus thuringiensis (Berliner, 1911) strains toxic to E. aurantiana. For this purpose, 47 B. thuringiensis strains were evaluated in selective bioassays using first instar larvae of E. aurantiana. The lethal concentration (LC50) of the most toxic strains was estimated, and the strains were characterized by morphological, biochemical, and molecular methods. Of the 47 strains tested, 10 caused mortality above 85% and showed mean lethal concentrations between 1.05E+7 and 1.54E+8 spores mL-1. The lowest LC50 values were obtained for the HD-1 standard strain and the BR145, BR83, BR52, and BR09 strains. The protein profile showed the presence of Cry proteins of 60, 65, 70, 80, and 130 kDa. The molecular characterization showed the presence of cry1, cry2, cry3, and cry11 genes. The morphological analysis identified three different crystalline inclusions: bipyramidal, round, and cuboidal. The cry1 and cry2 genes were the most frequent among the B. thuringiensis strains evaluated and encode Cry proteins toxic to insects of the order Lepidoptera, which agree with the toxicity results obtained by the selective bioassays against E. aurantiana. The results showed four different B. thuringiensis strains toxic to E. aurantiana at the same level as the HD-1 standard strain, and these strains have biotechnological potential for E. aurantiana control through the production of transgenic plants or the formulation of biopesticides. PMID- 27406594 TI - Exploring the Experience of Life Stress Among Black Women with a History of Fetal or Infant Death: a Phenomenological Study. AB - INTRODUCTION: Disparate birth outcomes among Black women continue to be a major public health problem. Whereas prior research has investigated the influence of stress on Black women's birth outcomes, few studies have explored how stress is experienced among Black women across the life course. The objectives of this study were to describe the experience of stress across the life course among Black women who reported a history of fetal or infant death and to identify stressful life events (SLE) that may not be represented in the widely used SLE inventory. METHODS: Using phenomenological, qualitative research design, in-depth interviews were conducted with six Black women in Kansas who experienced a fetal or infant death. RESULTS: Analyses revealed that participants experienced multiple, co-occurring stressors over the course of their lives and experienced a proliferation of stress emerging in early life and persisting into adulthood. Among the types of stressors cited by participants, history of sexual assault (trauma-related stressor) was a key stressful life event that is not currently reflected in the SLE inventory. CONCLUSION: Our findings highlight the importance of using a life-course perspective to gain a contextual understanding of the experiences of stress among Black women, particularly those with a history of adverse birth outcomes. Further research investigating Black women's experiences of stress and the mechanisms by which stress impacts their health could inform efforts to reduce disparities in birth outcomes. An additional focus on the experience and impact of trauma-related stress on Black women's birth outcomes may also be warranted. PMID- 27406595 TI - Atomic scale observation of oxygen delivery during silver-oxygen nanoparticle catalysed oxidation of carbon nanotubes. AB - To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars-van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes. PMID- 27406596 TI - Parental Reports of Infant and Child Eating Behaviors are not Affected by Their Beliefs About Their Twins' Zygosity. AB - Parental perception of zygosity might bias heritability estimates derived from parent rated twin data. This is the first study to examine if similarities in parental reports of their young twins' behavior were biased by beliefs about their zygosity. Data were from Gemini, a British birth cohort of 2402 twins born in 2007. Zygosity was assessed twice, using both DNA and a validated parent report questionnaire at 8 (SD = 2.1) and 29 months (SD = 3.3). 220/731 (8 months) and 119/453 (29 months) monozygotic (MZ) pairs were misclassified as dizygotic (DZ) by parents; whereas only 6/797 (8 months) and 2/445 (29 months) DZ pairs were misclassified as MZ. Intraclass correlations for parent reported eating behaviors (four measured at 8 months; five at 16 months) were of the same magnitude for correctly classified and misclassified MZ pairs, suggesting that parental zygosity perception does not influence reporting on eating behaviors of their young twins. PMID- 27406597 TI - Individual Differences in Exercise Behavior: Stability and Change in Genetic and Environmental Determinants From Age 7 to 18. AB - Exercise behavior during leisure time is a major source of health-promoting physical activity and moderately tracks across childhood and adolescence. This study aims to investigate the absolute and relative contribution of genes and the environment to variance in exercise behavior from age 7 to 18, and to elucidate the stability and change of genetic and shared environmental factors that underlie this behavior. The Netherlands Twin Register collected data on exercise behavior in twins aged approximately 7, 10, 12, 14, 16 and 18 years (N = 27,332 twins; 48 % males; 47 % with longitudinal assessments). Three exercise categories (low, middle, high) were analyzed by means of liability threshold models. First, a univariate model was fitted using the largest available cross-sectional dataset with linear and quadratic effects of age as modifiers on the means and variance components. Second, a simplex model was fitted on the longitudinal dataset. Heritability was low in 7-year-olds (14 % in males and 12 % in females), but gradually increased up to age 18 (79 % in males and 49 % in females), whereas the initially substantial relative influence of the shared environment decreased with age (from 80 to 4 % in males and from 80 to 19 % in females). This decrease was due to a large increase in the genetic variance. The longitudinal model showed the genetic effects in males to be largely stable and to accumulate from childhood to late adolescence, whereas in females, they were marked by both transmission and innovation at all ages. The shared environmental effects tended to be less stable in both males and females. In sum, the clear age-moderation of exercise behavior implies that family-based interventions might be useful to increase this behavior in children, whereas individual-based interventions might be better suited for adolescents. We showed that some determinants of individual differences in exercise behavior are stable across childhood and youth, whereas others come into play at specific ages. In view of the many benefits of regular exercise, identifying these determinants at specific ages should be a public health priority. PMID- 27406598 TI - A Multifunctional Surface That Simultaneously Balances Hydrophilic Enzyme Catalysis and Hydrophobic Water Repellency. AB - The compatibility of multiple functions at a single interface is difficult to achieve, but is even more challenging when the functions directly counteract one another. This study provides insight into the creation of a simultaneously multifunctional surface formed by balancing two orthogonal functions; water repellency and enzyme catalysis. A partially fluorinated thiol is used to impart bulk hydrophobicity on the surface, and an N-hydroxysuccinimide ester-terminated thiol provides a specific anchoring sites for the covalent enzyme attachment. Different ratios of the two thiols are mixed together to form amphiphilic self assembled monolayers, which are characterized with polarization-modulation infrared reflection-absorption spectroscopy and contact angle goniometry. The enzyme activity is measured by a fluorescence assay. With the results collected here, specific surface compositions are identified at which the orthogonal functions of water repellency and enzyme catalysis are balanced and exist simultaneously. An understanding of how to effectively balance orthogonal functions at surfaces can be extended to a number of higher-scale applications. PMID- 27406599 TI - Electrocardiogram Abnormalities of Caffeine Overdose. PMID- 27406601 TI - Multiple and Concurrent Arrhythmia. PMID- 27406600 TI - Signal Transducer and Activator of Transcription 3/MicroRNA-21 Feedback Loop Contributes to Atrial Fibrillation by Promoting Atrial Fibrosis in a Rat Sterile Pericarditis Model. AB - BACKGROUND: Postoperative atrial fibrillation is a frequent complication in cardiac surgery. The aberrant activation of signal transducer and activator of transcription 3 (STAT3) contributes to the pathogenesis of atrial fibrillation. MicroRNA-21 (miR-21) promotes atrial fibrosis. Recent studies support the existence of reciprocal regulation between STAT3 and miR-21. Here, we test the hypothesis that these 2 molecules might form a feedback loop that contributes to postoperative atrial fibrillation by promoting atrial fibrosis. METHODS AND RESULTS: A sterile pericarditis model was created using atrial surfaces dusted with sterile talcum powder in rats. The inflammatory cytokines interleukin (IL) 1beta, IL-6, transforming growth factor-beta, and tumor necrosis factor-alpha, along with STAT3 and miR-21, were highly upregulated in sterile pericarditis rats. The inhibition of STAT3 by S3I-201 resulted in miR-21 downregulation, which ameliorated atrial fibrosis and decreased the expression of the fibrosis-related genes, alpha-smooth muscle actin, collagen-1, and collagen-3; reduced the inhomogeneity of atrial conduction; and attenuated atrial fibrillation vulnerability. Meanwhile, treatment with antagomir-21 decreased STAT3 phosphorylation, alleviated atrial remodeling, abrogated sterile pericarditis induced inhomogeneous conduction, and prevented atrial fibrillation promotion. The culturing of cardiac fibroblasts with IL-6 resulted in progressively augmented STAT3 phosphorylation and miR-21 levels. S3I-201 blocked IL-6 induced the expression of miR-21 and fibrosis-related genes in addition to cardiac fibroblast proliferation. Transfected antagomir-21 decreased the IL-6-induced cardiac fibroblast activation and STAT3 phosphorylation. The overexpression of miR-21 in cardiac fibroblasts caused the upregulation of STAT3 phosphorylation, enhanced fibrosis-related genes, and increased cell numbers. CONCLUSIONS: Our results have uncovered a novel reciprocal loop between STAT3 and miR-21 that is activated after heart surgery and can contribute to atrial fibrillation. PMID- 27406602 TI - Left Atrial Appendage Electrical Isolation and Concomitant Device Occlusion to Treat Persistent Atrial Fibrillation: A First-in-Human Safety, Feasibility, and Efficacy Study. AB - BACKGROUND: Left atrial appendage (LAA) electric isolation is reported to improve persistent atrial fibrillation (AF) ablation outcomes. However, loss of LAA mechanical function may increase thromboembolic risk. Concomitant LAA electric isolation and occlusion as part of conventional AF ablation has never been tested in humans. We therefore evaluated the feasibility, safety, and efficacy of LAA electric isolation and occlusion in patients undergoing long-standing persistent AF ablation. METHODS AND RESULTS: Patients with long-standing persistent AF (age, 68+/-7 years; left atrium diameter, 46+/-3 mm; and AF duration, 25+/-15 months) underwent AF ablation, LAA electric isolation, and occlusion. Outcomes were compared with a balanced (1:2 ratio) control group who had AF ablation alone. Among 22 patients who underwent ablation, LAA electric isolation was possible in 20. Intraprocedural LAA reconnection occurred in 17 of 20 (85%) patients, predominantly at anterior and superior locations. All were reisolated. LAA occlusion was successful in all 20 patients. There were no major periprocedural complications. Imaging at 45 days and 9 months confirmed satisfactory device position and excluded pericardial effusion. One of twenty (5%) patients had a gap of >=5 mm requiring anticoagulation. Nineteen of twenty (95%) patients stopped warfarin at 3 months. Without antiarrhythmic drugs, freedom from AF at 12 months after a single procedure was significantly higher in the study group (19/20, 95%) than in the control group (25/40, 63%), P=0.036. Freedom from atrial arrhythmias was demonstrated in 12 of 20 (60%) and 18 of 20 (90%) patients after 1 and <=2 procedures (mean, 1.3), respectively. CONCLUSIONS: Persistent AF ablation, LAA electric isolation, and mechanical occlusion can be performed concomitantly. This technique may improve the success of persistent AF ablation while obviating the need for chronic anticoagulation. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02028130. PMID- 27406603 TI - Identification of Concealed and Manifest Long QT Syndrome Using a Novel T Wave Analysis Program. AB - BACKGROUND: Congenital long QT syndrome (LQTS) is characterized by QT prolongation. However, the QT interval itself is insufficient for diagnosis, unless the corrected QT interval is repeatedly >=500 ms without an acquired explanation. Further, the majority of LQTS patients have a corrected QT interval below this threshold, and a significant minority has normal resting corrected QT interval values. Here, we aimed to develop and validate a novel, quantitative T wave morphological analysis program to differentiate LQTS patients from healthy controls. METHODS AND RESULTS: We analyzed a genotyped cohort of 420 patients (22+/-16 years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a novel, proprietary T wave analysis program that quantitates subtle changes in T wave morphology. The top 3 discriminating features in each ECG lead were determined and the lead with the best discrimination selected. Classification was performed using a linear discriminant classifier and validated on an untouched cohort. The top 3 features were Tpeak-Tend interval, T wave left slope, and T wave center of gravity x axis (last 25% of the T wave). Lead V6 had the best discrimination. It could distinguish 86.8% of LQTS patients from healthy controls. Moreover, it distinguished 83.33% of patients with concealed LQTS from controls, despite having essentially identical resting corrected QT interval values. CONCLUSIONS: T wave quantitative analysis on the 12-lead surface ECG provides an effective, novel tool to distinguish patients with either LQT1/LQT2 from healthy matched controls. It can provide guidance while mutation-specific genetic testing is in motion for family members. PMID- 27406604 TI - Impact of New Technologies and Approaches for Post-Myocardial Infarction Ventricular Tachycardia Ablation During Long-Term Follow-Up. AB - BACKGROUND: During the past years, many innovations have been introduced to facilitate catheter ablation of post-myocardial infarction ventricular tachycardia. However, the predictors of outcome after ablation were not thoroughly studied. METHODS AND RESULTS: From 2009 to 2013, consecutive patients referred for post-myocardial infarction ventricular tachycardia ablation were included. The end point of the procedure was complete elimination of local abnormal ventricular activities (LAVA) and ventricular tachycardia (VT) noninducibility. The predictors of outcome with primary end point of VT recurrence were assessed. A total of 125 patients were included (age: 64+/-11 years; 7 women) for 142 procedures. The left ventricle was accessed via transseptal, retrograde aortic, and epicardial approaches in 87%, 33%, and 37% of patients, respectively. Three-dimensional electroanatomical mapping system was used in 70%, multipolar catheter in 51%, and real-time image integration in 38% (from magnetic resonance imaging in 39% and multidetector computed tomography in 93%) of patients. Before ablation, VT was inducible in 75%, and endocardial/epicardial LAVA were present in 88%/75%. After ablation, complete LAVA elimination was achieved in 60%, and VT noninducibility in 83%. During a median follow-up of 850 days (interquartile range, 439-1707), VT recurrence was observed in 36%. Multivariable analysis identified 3 independent outcome predictors: the ability to achieve complete LAVA elimination (R(2)=0.29; P<0.0001; risk ratio=0.52 [0.38-0.70]), the use of real-time image integration (R(2)=0.21; P=0.0006; risk ratio=0.49 [0.33-0.74]), and the use of multipolar catheters (R(2)=0.08; P=0.05; risk ratio=0.75 [0.56-1.00]). CONCLUSIONS: Achievement of complete LAVA elimination and use of scar integration from imaging and multipolar catheters to focus high-density mapping are independent predictors of VT-free survival after catheter ablation for post-myocardial infarction ventricular tachycardia. PMID- 27406605 TI - Outcomes 1 Year After Implantable Cardioverter-Defibrillator Lead Abandonment Versus Explantation for Unused or Malfunctioning Leads: A Report from the National Cardiovascular Data Registry. AB - BACKGROUND: Patients with an unused or malfunctioning implantable cardioverter defibrillator (ICD) lead may have the lead either abandoned or explanted; yet there are limited data on the comparative acute and longer-term safety of these 2 approaches. METHODS AND RESULTS: We examined in-hospital events among 24 908 subject encounters using propensity score 1:1 matching for ICD lead abandonment or explantation in the National Cardiovascular Data Registry (NCDR) ICD Registry (April 2010 to June 2014). Relative to patients undergoing lead abandonment, patients undergoing lead explantation had more in-hospital procedure-related complications: 2.19% (n=273) versus 3.77% (n=469; P<0.001), respectively. Similarly, patients undergoing lead explantation had slightly higher rates of in hospital death: 0.21% (n=26) versus 0.64% (n=80; P<0.001), respectively. At 1 year in a Medicare subset for survival, there was a trend of increased mortality in the explantation group (11% versus 8%; P=0.06). In the Medicare subset analyzed for postprocedure complications, there was no difference with respect to 6-month bleeding (4.80% in both the groups), tamponade (0.38% versus 0.58%), infection (1.34% versus 3.07%), upper extremity thrombosis (0.77% versus 0.96%), pulmonary embolism (0.38% versus 0.96%), or urgent surgery (1.15% for both the groups; P>0.05 for all). CONCLUSIONS: After matching, patients undergoing removal of an unused or malfunctioning ICD lead had slightly higher in-hospital complications and deaths than those with a lead abandonment strategy. Although the 1-year mortality risk was slightly higher in the lead explantation group, this difference was not statistically significant and may be explained by chance. PMID- 27406607 TI - Left Atrial Appendage After Electrical Isolation: To Occlude or Not To Occlude, That Is the Question. PMID- 27406606 TI - Retrograde Coronary Venous Ethanol Infusion for Ablation of Refractory Ventricular Tachycardia. AB - BACKGROUND: Radiofrequency ablation (RFA) of ventricular tachycardia (VT) can fail because of inaccessibility to the VT substrate. Transarterial coronary ethanol ablation can be effective but entails arterial instrumentation risk. We hypothesized that retrograde coronary venous ethanol ablation can be an alternative bail-out approach to failed VT RFA. METHODS AND RESULTS: Out of 334 consecutive patients undergoing VT/premature ventricular contraction ablation, 7 patients underwent retrograde coronary venous ethanol ablation. Six out of 7 patients had failed RFA attempts (including epicardial in 3). Coronary venogram guided venous mapping was performed using a 4F quadripolar catheter or an alligator-clip-connected angioplasty wire. Targeted veins included those with early presystolic potentials and pace-maps matching VT/premature ventricular contraction. An angioplasty balloon (1.5-2*6 mm) was used to deliver 1 to 4 cc of 98% ethanol into a septal branch of the anterior interventricular vein in 5 patients with left ventricular summit VT, a septal branch of the middle cardiac vein, and a posterolateral coronary vein (n=1 each). The clinical VT was successfully ablated acutely in all patients. There were no complications of retrograde coronary venous ethanol ablation, but 1 patient developed pericardial and pleural effusion attributed to pericardial instrumentation. On follow-up of 590+/-722 days, VT recurred in 4 out of 7 patients, 3 of whom were successfully reablated with RFA. CONCLUSIONS: Retrograde coronary venous ethanol ablation is safe and feasible as a bail-out approach to failed VT RFA, particularly those originating from the left ventricular summit. PMID- 27406608 TI - Resolving Myocardial Activation With Novel Omnipolar Electrograms. AB - BACKGROUND: With its inherent limitations, determining local activation times has been the basis of cardiac mapping for over a century. Here, we introduce omnipolar electrograms that originate from the natural direction of a travelling wave and from which instantaneous conduction velocity amplitude and direction can be computed at any single location without first determining activation times. We sought to validate omnipole-derived conduction velocities and explore potential application for localization of sources of arrhythmias. METHODS AND RESULTS: Electrograms from omnipolar mapping were derived and validated using 4 separate models and 2 independent signal acquisition methodologies. We used both electric signals and optical signals collected from monolayer cell preparations, 3 dimensional constructs built with cardiomyocytes derived from human embryonic stem cells, simultaneous optical and electric mapping of rabbit hearts, and in vivo pig electrophysiology studies. Conduction velocities calculated from omnipolar electrograms were compared with wavefront propagation from optical and electric-mapping studies with a traditional local activation time-based method. Bland-Altman analysis revealed that omnipolar measurements on optical data were in agreement with local activation time methods for wavefront direction and velocity within 25 cm/s and 30 degrees , respectively. Similar agreement was also found on electric data. Furthermore, mathematical operations, such as curl and divergence, were applied to omnipole-derived velocity vector fields to locate rotational and focal sources, respectively. CONCLUSIONS: Electrode orientation independent cardiac wavefront trajectory and speed at a single location for each cardiac activation can be determined accurately with omnipolar electrograms. Omnipole-derived vector fields, when combined with mathematical transforms may aid in real-time detection of cardiac activation sources. PMID- 27406609 TI - Costs and Mortality Associated With Multidrug-Resistant Healthcare-Associated Acinetobacter Infections. AB - BACKGROUND Our objective was to estimate the per-infection and cumulative mortality and cost burden of multidrug-resistant (MDR) Acinetobacter healthcare associated infections (HAIs) in the United States using data from published studies. METHODS We identified studies that estimated the excess cost, length of stay (LOS), or mortality attributable to MDR Acinetobacter HAIs. We generated estimates of the cost per HAI using 3 methods: (1) overall cost estimates, (2) multiplying LOS estimates by a cost per inpatient-day ($4,350) from the payer perspective, and (3) multiplying LOS estimates by a cost per inpatient-day from the hospital ($2,030) perspective. We deflated our estimates for time-dependent bias using an adjustment factor derived from studies that estimated attributable LOS using both time-fixed methods and either multistate models (70.4% decrease) or matching patients with and without HAIs using the timing of infection (47.4% decrease). Finally, we used the incidence rate of MDR Acinetobacter HAIs to generate cumulative incidence, cost, and mortality associated with these infections. RESULTS Our estimates of the cost per infection were $129,917 (method 1), $72,025 (method 2), and $33,510 (method 3). The pooled relative risk of mortality was 4.51 (95% CI, 1.10-32.65), which yielded a mortality rate of 10.6% (95% CI, 2.5%-29.4%). With an incidence rate of 0.141 (95% CI, 0.136-0.161) per 1,000 patient-days at risk, we estimated an annual cumulative incidence of 12,524 (95% CI, 11,509-13,625) in the United States. CONCLUSION The estimates presented here are relevant to understanding the expenditures and lives that could be saved by preventing MDR Acinetobacter HAIs. Infect Control Hosp Epidemiol 2016;1-7. PMID- 27406610 TI - Accuracy of pre-contrast imaging in abdominal magnetic resonance imaging of pediatric oncology patients. AB - BACKGROUND: Safety concerns are increasingly raised regarding the use of gadolinium-based contrast media for MR imaging. OBJECTIVE: To determine the accuracy of pre-contrast abdominal MR imaging for lesion detection and characterization in pediatric oncology patients. MATERIALS AND METHODS: We included 120 children (37 boys and 83 girls; mean age 8.94 years) referred by oncology services. Twenty-five had MRI for the first time and 95 were follow-up scans. Two authors independently reviewed pre-contrast MR images to note the following information about the lesions: location, number, solid vs. cystic and likely nature. Pre- and post-contrast imaging reviewed together served as the reference standard. RESULTS: The overall sensitivity was 88% for the first reader and 90% for the second; specificity was 94% and 91%; positive predictive value was 96% and 94%; negative predictive value was 82% and 84%; accuracy of pre contrast imaging for lesion detection as compared to the reference standard was 90% for both readers. The difference between mean number of lesions detected on pre-contrast imaging and reference standard was not significant for either reader (reader 1, P = 0.072; reader 2, P = 0.071). There was substantial agreement (kappa values of 0.76 and 0.72 for readers 1 and 2) between pre-contrast imaging and reference standard for determining solid vs. cystic lesion and likely nature of the lesion. The addition of post-contrast imaging increased confidence of both readers significantly (P < 0.0001), but the interobserver agreement for the change in confidence was poor (kappa 0.12). CONCLUSION: Pre-contrast abdominal MR imaging has high accuracy in lesion detection in pediatric oncology patients and shows substantial agreement with the reference standard for characterization of lesions. Gadolinium-based contrast media administration cannot be completely eliminated but can be avoided in many cases, with the decision made on a case-by case basis, taking into consideration location and type of tumor. PMID- 27406612 TI - Moving the Frontiers of Cancer Chemotherapy for Solid Tumors by Changing the Scope of Drug Development. AB - Our increasing knowledge on the pathogenetic mechanisms involved in the growth of cancer cells and on the molecular basis of cancer has influenced the development of anticancer agents. The realization that new targets should be evaluated for anti-cancer drug treatment has a.o. led to the introduction of the taxoids and topoisomerase I inhibitors. Attacking the known targets in a more sophisticated way led to the development of drugs with increased target specificity like Tomudex and Gemcitabine. Finally, using old drugs more efficiently by using pharmacokinetic and pharmacodynamic ananlysis hold a promise for the near future. PMID- 27406611 TI - The many shades of enhancement: timing of post-gadolinium images strongly influences the scoring of juvenile idiopathic arthritis wrist involvement on MRI. AB - BACKGROUND: Potential long-term side effects of treatment for juvenile idiopathic arthritis are concerning. This has necessitated accurate tools, such as MRI, to monitor treatment response and allow for personalized therapy. OBJECTIVE: To examine the extent to which timing of post-contrast MR images influences the scoring of inflammatory change in the wrist in children with juvenile idiopathic arthritis. MATERIALS AND METHODS: We studied two sets of post-contrast 3-D gradient echo MRI series of the wrist in 34 children with juvenile idiopathic arthritis. These images were obtained immediately after administration of intravenous contrast material and again after approximately 10 min. The dataset was drawn from a prospective multicenter project conducted 2006-2010. We assessed five wrist locations for synovial enhancement, effusion and overall inflammation. Examinations were scored by one radiologist in two sessions - the first was based on the early post-contrast images, and the later session, for which the previous findings were masked, was based on the later post-contrast images. RESULTS: Fifty two of the 170 locations (30.6%) received a higher synovial enhancement score based on the late post-contrast images as compared to the early images. Sixty of the 170 (35%) locations received a higher total inflammation score. The mean scores of synovial enhancement and total inflammation were significantly higher when based on the late post-contrast images as compared to the early post contrast images. CONCLUSION: An MRI-based scoring system for the presence and degree of synovitis should be based on a standardized MR-protocol with a fixed interval between intravenous contrast injection and post-contrast images. PMID- 27406613 TI - Protein Turnover, Energy Expenditure and Body Composition in Patients with Acute Leukaemia Undergoing Chemotherapy. AB - 1. Measurements of whole body protein turnover using the (13)C-leucine tracer technique, of body composition using anthropometric measurements and DEXA scanning, and of resting energy expenditure (REE) assessed by indirect calorimetry were made in 8 patients with acute leukaemia undergoing a single course of chemotherapy. Measurements were made in the post absorptive state immediately before chemotherapy and were repeated close to the time of discharge from hospital (mean days in hospital 31 +/- 4.3, range 22-35), a mean of 23 +/- 4.8 days after completion of chemotherapy. 2. The mean weight loss was 3.63kg (P < 0.001) with significant reductions in the mean non dominant mid arm circumference (1.29cm, P < 0.01), biceps (0.7mm, P < 0.01) and triceps (1.9mm, P < 0.05) skinfold thicknesses. DEXA scanning showed a reduction of mean body fat (1.22kg, P < 0.05) and lean tissue (1.85kg, P < 0.01). 3. There was a reduction in whole body leucine flux (Q) by 35% (P < 0.01) and synthesis (S) by 40% (P < 0.001) with no change in catabolism (C) over the course of admission. 4. There were no significant changes in REE. PMID- 27406615 TI - Interleukin-11: Its Characterization and Physiological Effects. PMID- 27406614 TI - Granulocyte-Macrophage Colony-Stimulating Factor in Newly Diagnosed Adult Patients with Acute Lymphoblastic Leukemia Treated with Conventional Chemotherapy. AB - Twenty consecutive adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) were treated with conventional therapy consisting of daunorubicin, vincristine, prednisone and L-asparaginase in standard doses. Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a single subcutaneous daily dose of 5 microgram per kilogram body weight for fourteen days starting on day 7 of chemotherapy. Twenty two adult patients with acute lymphoblastic leukemia and similar risk characteristics who received the same chemotherapeutic regimen without GM-CSF served as a historical control group. The complete remission rate and the rate of early mortality were similar in both groups of patients. Patients treated with GM-CSF showed significantly faster neutrophil recovery above 0.5 * 10(9)/L than the control patients (P < 0.005). The incidence of febrile episodes and the rate of documented infection were similar in the two groups of patients. PMID- 27406616 TI - Unexpected Epithelial Membrane Antigen (EMA) and Cytokeratin Expression in a Case of Infantile Acute Monoblastic Leukaemia. AB - A previously healthy eleven month old male Malay infant presented with fever, upper respiratory tract infection and right knee swelling. Pallor, bilateral proptosis, hepatosplenomegaly, multiple scalp swellings and a right cheek swelling were observed. Investigations revealed that he had acute monoblastic leukemia or FAB M5a. Immunophenotyping by flow cytometry showed that the blast cells were positive for CD45, CD13, CD33, HLA-DR, CDllc, CD71, EMA, and Cytokeratin. They were negative for CD34, CD19, CD10, CD22, CD2, CD3, CD4, CD7, CD8, CD61, NK, Glycophorin A, and CD14. The monoblasts were used to evaluate anti EMA and anti-cytokeratin. They were unexpectedly found to be positive. Acute monoblastic leukaemias are well known to show extramedullary infiltration and this may be their primary mode of presentation. Thus, in immunochemostry, when using EMA and cytokeratin expression in the differential diagnosis of neoplastic diseases, it is important to consider that monoblasts may express these markers as illustrated by this case. PMID- 27406617 TI - Hereditary Thrombophilic Disease Associated with Defects in the Protein C Anticoagulant System. PMID- 27406618 TI - Nitrite and Nitrate Plasma Levels, as Markers for Nitric Oxide Synthesis, in Thrombotic Thrombocytopenic Purpura (TTP). AB - The enhanced platelet aggregation and thrombosis occurring in TTP is probably due to an unbalance between agents insulting endothelial integrity and natural antithrombotic factors, such as NO. Using a sensitive and specific HPLC assay, we tested the hypothesis of NO involvement in TTP, comparing NO production, as the stable end-products nitrites and nitrates, in the plasma of 29 TTP patients and of 29 healthy subjects matched for sex and age. Average nitrate titer was 25.868 MUM/L in the TTP group vs 24.234 MUM/L in the control group (p = n.s.), while nitrite were undetectable in both groups. Moreover, nitrate titers did not correlate with hemoglobin value, platelet count, LDH values, or with Rose and Eldor's severity score. In conclusion, even though the enhanced platelet aggregation observed in TTP could be due to reduced natural antithrombotic substances, NO involvement in the pathogenesis of TTP appears unlikely. PMID- 27406619 TI - Enhanced Erythropoietin Response to Acute Hypoxemia in Mice with Pharmacological Depression of Erythropoiesis. AB - The recent report of a depression of stimulated production of erythropoietin (EPO) in mice with enhanced erythropoiesis suggests that unknown mechanism (s) other than hypoxia may be involved in the regulation of EPO formation. The present study was thus designed to investigate EPO production during acute hypoxemia in a mouse model in which the oxygen-carrying capacity of blood, the plasma EPO level, and the plasma EPO half-life were within normal values in spite of a marked depression of the red cell production rate (RCPR) induced by cyclophosphamide (CP) administration. Injection of 100 mg/Kg of the drug into adult female CF-1 mice that previously received 0.4 ml of packed red cells depressed markedly the 24-hour RBC 59Fe uptake without affecting the plasma immunoreactive EPO level and the plasma disappearance of 1251-labeled recombinant human EPO. The EPO production rate, calculated from the change in plasma EPO levels and the estimated EPO clearance rate, after 4 h of exposure to hypobaric air was about 2.8 times higher in mice with CP-induced inhibition of the RCPR than in mice with normal RCPR. The results support the hypothesis that the EPO production rate in mammals is not only related to the oxygen supply to the tissues relative to their oxygen needs (main stimulus) but also to the erythroid activity of the marrow (modulatory action). PMID- 27406621 TI - The Diagnosis and Treatment of Iron Deficiency Anaemia. PMID- 27406620 TI - Prenatal Diagnosis of beta-Thalassemia Using Multiplex Allele-Specific Amplification (MASPCR) in Chinese Families. AB - Combining allele-specific amplification (ASPCR) with multiplex PCR, we developed a new approach-multiplex allele-specific amplification (MASPCR) to detect five common types of beta-thalassemia mutations (CD 41-42(-4bp), CD 17 A->T, CD 71-72 (+ A), -28 A-> G and IVS-2-654 C-> T) which account for approximately 80% of all beta-thalassemia alleles in Chinese individuals. Using this technique, prenatal diagnoses were performed for ten pregnancies at risk for beta-thalassemia. All the results were confirmed by PCR/ASO probe hybridization or DNA sequencing. This study suggests that this method is a simple, accurate approach that may further improve the prevention programs for beta-thalassemia that have already dramatically lowered the birth rate of affected children in some parts of the world. PMID- 27406622 TI - Beard infantile hemangioma and subglottic involvement: are median pattern and telangiectatic aspect the clue? AB - BACKGROUND: Identification of patient at risk of subglottic infantile hemangioma (IH) is challenging because subglottic IH can grow fast and cause airway obstruction with a fatal course. OBJECTIVE: To refine the cutaneous IH pattern at risk of subglottic IH. METHODS: Prospective and retrospective review of patients with cutaneous IH involving the beard area. IHs were classified in the bilateral pattern group (BH) or in the unilateral pattern group (UH). Infantile hemangioma topography, subtype (telangiectatic or tuberous), ear, nose and throat (ENT) manifestations and subglottic involvement were recorded. RESULTS: Thirty-one patients (21 BH and 10 UH) were included during a 20-year span. Nineteen patients (16 BH and 3 UH) had subglottic hemangioma. BH and UH group overlap on the median pattern (tongue, gum, lips, chin and neck). Median pattern, particularly the neck area and telangiectatic subtype of IH were significantly associated with subglottic involvement. CONCLUSION: Patients presenting with telangiectatic beard IH localized on the median area need early ENT exploration. They should be treated before respiratory symptoms occur. PMID- 27406623 TI - Kinetic studies of phosphoester hydrolysis promoted by a dimeric tetrazirconium(iv) Wells-Dawson polyoxometalate. AB - The catalytic hydrolysis of a phosphoester bond in the DNA-model substrate 4 nitrophenyl phosphate (NPP) promoted by Zr(iv)-substituted Wells-Dawson Na14[Zr4(P2W16O59)2(MU3-O)2(OH)2(H2O)4].57H2O polyoxometalate (ZrWD 4 : 2) was followed by means of (1)H and (31)P NMR spectroscopy. The hydrolytic reaction proceeded with a rate constant of 8.44 (+/-0.36) * 10(-5) s(-1) at pD 6.4 and 50 degrees C, representing a 300-fold rate enhancement in comparison with the spontaneous hydrolysis of NPP (kobs = 2.81 (+/-0.25) * 10(-7) s(-1)) under the same reaction conditions. The ZrWD 4 : 2 was also active towards hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) and the RNA model substrate 2-hydroxypropyl-4 nitrophenyl phosphate (HPNP). The pD dependence of kobs shows that the rate constants for NPP hydrolysis decrease significantly when the pD values of the reaction mixtures increase. The formation constant (Kf = 190 M(-1)) and catalytic rate constant (kc = 6.40 * 10(-4) s(-1)) for the NPP-ZrWD 4 : 2 complex, activation energy (Ea) of 110.15 +/- 7.06 kJ mol(-1), enthalpy of activation (DeltaH(?)) of 109.03 +/- 6.86 kJ mol(-1), entropy of activation (DeltaS(?)) of 15.20 +/- 2.49 J mol(-1) K(-1), and Gibbs activation energy (DeltaG(?)) of 104.32 +/- 6.09 kJ mol(-1) at 37 degrees C were calculated from kinetic studies. The recyclability of ZrWD 4 : 2 was examined by adding an extra amount (5.0 mM) of NPP twice to a fully hydrolyzed mixture of 5.0 mM NPP and 1.0 mM ZrWD 4 : 2. The interaction between ZrWD 4 : 2 and the P-O bond of NPP was evidenced by a change in the (31)P chemical shift of the (31)P atom in NPP upon addition of ZrWD 4 : 2. Based on (31)P NMR experiments and the kinetic studies, a mechanism for NPP hydrolysis promoted by ZrWD 4 : 2 has been proposed. PMID- 27406625 TI - When the falls expert becomes the fall risk patient: Through the looking-glass. PMID- 27406624 TI - Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination. AB - DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3(+) CD25(+) CD4(+) Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8(+) T cells. We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced K(b)/A12-21-monospecific CD8(+) T cells and autoimmune diabetes. A pCI/ppinsDeltaA12-21 vector (lacking the critical K(b)/A12-21 epitope) did not induce autoimmune diabetes but elicited a systemic Foxp3(+) CD25(+) Treg cell immunity that suppressed diabetes induction by a subsequent injection of the diabetogenic pCI/ppins. TGF-beta expression was significantly enhanced in the Foxp3(+) CD25(+) Treg cell population of vaccinated/ppins-primed mice. Ablation of Treg cells in vaccinated/ppins-primed mice by anti-CD25 antibody treatment abolished the protective effect of the vaccine and enabled diabetes induction by pCI/ppins. Adoptive transfer of Treg cells from vaccinated/ppins-primed mice into PD-L1(-/-) hosts efficiently suppressed diabetes induction by pCI/ppins. We narrowed down the Treg-stimulating domain to a 15-residue ppins76-90 peptide. Vaccine-induced Treg cells thus play a crucial role in the control of de novo primed autoreactive effector CD8(+) T cells in this diabetes model. PMID- 27406626 TI - End of life care in nursing homes: Translating focus group findings into action. AB - Therapeutic options for nursing home residents focus on functional improvement, while inadequate hospital admissions in the dying phase are frequent. The aim of this study was to explore views, attitudes, and concerns among staff and to embark on a process that facilitates end-of-life care on an institutional level. Three focus group interviews were conducted with nursing home staff (nurses, care managers, physicians). The discussants (22) expressed the following issues: workload; ethical conflicts; additional resources; "living palliative care"; deleterious effect of restorative aims; lack of training; fear; knowledge and skills; rituals; lack of attachment, frustration, and abuse; team; discouragement; resilience enhanced by good care; style of communication; avoidance; the "palliative status"; legal concerns and hospital admissions. Nursing home staff expressed willingness to care for the dying. Providing good end of life care may promote professional resilience and personal integrity. Therefore, team issues, fears, and avoidance should be addressed. PMID- 27406627 TI - Involucratusins A-H: Unusual Cadinane Dimers from Stahlianthus involucratus with Multidrug Resistance Reversal Activity. AB - Three novel cadinane dimers, involucratusins A-C (1-3), five unique nor-cadinane dimers, involucratusins D-H (4-8), together with a known compound (9) were isolated from the rhizomes of Stahlianthus involucratus. Their challenging structures and absolute configurations were determined by spectroscopic data, CD experimentation, chemical conversions and single-crystal X-ray diffraction. Compounds 1-3 are unusual cadinane dimers with new connection and novel cores. Compound 4 is a unique nor-cadinane-dimer, and 5 and 6 are two pairs of hemiketal racemates with novel dinor-cadinane-dimer backbone. Compounds 7 and 8 represent unusual dodecanor-cadinane-dimer and tetradecanor-cadinane-dimer carbon skeletons, respectively. The possible biogenetic pathways of 1-8 were proposed, involving nucleophilic addition, SN2 nucleophilic displacement, [3 + 3] benzannulation, oxidative cleavage, decarboxylation, and oxidative phenol coupling reactions. Multidrug resistance (MDR) reversal activity assay of the isolates were evaluated in doxorubicin-resistant human breast cancer cells (MCF 7/DOX). The combined use of these novel cadinane dimers at a concentration of 10 MUM increased the cytotoxicity of doxorubicin by 2.2-5.8-fold. It is the first report about the MDR reversal activity of cadinane dimers. PMID- 27406628 TI - Integrating engineering principles into the medico-legal investigation of a rare fatal rollover car accident involving complex dynamics. AB - Rollover car accidents can be the result of forceful steering or hitting an obstacle that acts like a ramp. Mortality from this type of car accident is particularly high, especially when occupants are thrown out of the vehicle. We report a case of a 67-year-old man who died after a rollover accident that occurred when he was driving a car equipped with a glass moonroof. He was found inside his car with his safety belt correctly fastened and the roof shattered. At autopsy, a wide avulsion injury of the head was observed, which was associated with an atlanto-axial dislocation and full-thickness fracture of the cervical body and posterior facet joints of the seventh cervical vertebra. The data collected at the scene of the accident were integrated with the autopsy results to yield a forensic engineering reconstruction. This reconstruction elucidated the dynamics of the event and correctly ascribed the lesions observed at autopsy to the phases of the rollover. Afterward, an analysis of the scientific literature concerning rollover crash tests was conducted to understand why the driver sustained fatal injuries even though his seatbelt was properly fastened. PMID- 27406629 TI - Mammography and MRI for screening women who underwent chest radiation therapy (lymphoma survivors): recommendations for surveillance from the Italian College of Breast Radiologists by SIRM. AB - Women who underwent chest radiation therapy (CRT) during pediatric/young-adult age (typically, lymphoma survivors) have an increased breast cancer risk, in particular for high doses. The cumulative incidence from 40 to 45 years of age is 13-20 %, similar to that of BRCA mutation carriers for whom contrast-enhanced magnetic resonance imaging (MRI) is recommended. However, in women who underwent CRT, MRI sensitivity is lower (63-80 %) and that of mammography higher (67-70 %) than those observed in women with hereditary predisposition, due to a higher incidence of ductal carcinoma in situ with microcalcifications and low neoangiogenesis. A sensitivity close to 95 % can be obtained only using mammography as an adjunct to MRI. Considering the available evidence, women who underwent CRT before 30 receiving a cumulative dose >=10 Gy should be invited after 25 (or, at least, 8 years after CRT) to attend the following program: 1. interview about individual risk profile and potential of breast imaging; 2. annual MRI using the same protocol recommended for women with hereditary predisposition; 3. annual bilateral two-view full-field digital mammography or digital breast tomosynthesis (DBT) with synthetic 2D reconstructions. Mammography and MRI can be performed at once or alternately every 6 months. In the case of MRI or contrast material contraindications, ultrasound will be performed instead of MRI. Reporting using BI-RADS is recommended. At the age for entering population screening, the individual risk profile will be discussed with the woman about opting for only mammography/DBT screening or for continuing the intensive protocol. PMID- 27406630 TI - Magnetic resonance imaging features of idiopathic granulomatous mastitis: is there any contribution of diffusion-weighted imaging in the differential diagnosis? AB - PURPOSE: To identify the magnetic resonance imaging (MRI) appearance of idiopathic granulomatous mastitis, and the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in distinguishing idiopathic granulomatous mastitis (IGM) from malignant breast lesions. MATERIAL AND METHODS: A total of 37 women (mean age 36 + 8; range 20-67 years) with histopathologic diagnoses of idiopathic granulomatous mastitis were enrolled in the study. Five patients had bilateral IGM, which were evaluated as ten cases. Dynamic MRI findings were categorized as enhancing mass lesion, non-mass enhancement, or both together. The frequency of quadrant involvement, retroareolar involvement, accompanying abscess, ductal ectasia, skin thickening, breast edema, extension to pectoral muscle, and presence of fistula were investigated. The mean apparent diffusion coefficient (ADC) values for lesions, contralateral normal breast parenchyma, pectoralis major muscle, and sternum were measured in patients with invasive cancers (n = 42) and those with mastitis (n = 42). The ADC ratio of the lesions to the contralateral normal breast parenchyma, pectoralis major muscle, and sternum were determined. RESULTS: The findings of idiopathic granulomatous mastitis on MRI were total (in all quadrants) or wide (2 or 3 quadrants) in 30 (71.5 %), retroareolar space involvement in 28 (66.7 %), skin thickening in 21 (50 %), breast edema in 21 (50 %), extension to pectoral muscle in 18 (42.9 %), accompanying abscess formation in 33 (78 %), ductal ectasia in 17 (40.5 %), and fistulas in 13 (31 %). On dynamic contrast-enhanced MRI, 69 % of the patients had mass appearance of IGM. The most frequent enhancement patterns were rim enhancement in 20 (78 %) in masses and clustered ring in 11 (48 %) in non-mass lesions. Early enhancement pattern of IGM was obtained as 'slow' in 29 cases (69 %), 'medium' in 11 cases (26.1) and 'rapid' in 2 (5 %) cases. Time-signal intensity curves were detected as Type-1 in 27 cases (64 %) and Type-2 in 15 cases (36 %). IGM showed significantly lower mean ADC values when compared with the normal parenchyma. When IGM was compared with malignancy, mastitis ADC was 0.98 +/- 0.188 * 10-3, and invasive cancer ADC was 0.95 +/- 0.229 * 10-3. The difference in ADC values of mastitis and invasive cancers proved not to be significant (P = 0.185). Our results had no discriminatory power for IGM versus malignant lesions for either ADC values and ADC ratios of normal breast parenchyma, pectoralis major muscle, and sternum. CONCLUSION: Although not characteristic for idiopathic granulomatous mastitis, masses with rim enhancement or clustered-ring non-mass lesions with segmental distribution on MRI are the most common features of the disease. Ductal ectasia and periductal enhancement were commonly accompanying; this and kinetic analysis are valuable findings for distinguishing IGM from invasive cancer. IGM shows similar ADC values to invasive cancers despite being benign, DW-MRI is not helpful in the differentiation with malignant lesions. PMID- 27406631 TI - Nanogenerators consisting of direct-grown piezoelectrics on multi-walled carbon nanotubes using flexoelectric effects. AB - We report the first attempt to prepare a flexoelectric nanogenerator consisting of direct-grown piezoelectrics on multi-walled carbon nanotubes (mwCNT). Direct grown piezoelectrics on mwCNTs are formed by a stirring and heating method using a Pb(Zr0.52Ti0.48)O3 (PZT)-mwCNT precursor solution. We studied the unit cell mismatch and strain distribution of epitaxial PZT nanoparticles, and found that lattice strain is relaxed along the growth direction. A PZT-mwCNT nanogenerator was found to produce a peak output voltage of 8.6 V and an output current of 47 nA when a force of 20 N is applied. Direct-grown piezoelectric nanogenerators generate a higher voltage and current than simple mixtures of PZT and CNTs resulting from the stronger connection between PZT crystals and mwCNTs and an enhanced flexoelectric effect caused by the strain gradient. These experiments represent a significant step toward the application of nanogenerators using piezoelectric nanocomposite materials. PMID- 27406632 TI - Controlled plasmon enhanced fluorescence by silver nanoparticles deposited onto nanotube arrays. AB - Three-dimensional (3D) plasmonic nanostructures of porous alumina array (PAA) with silver nanoparticles (AgNPs) were prepared for enhancing fluorescence emission. In order to avoid fluorescence quenching effects and obtain clear fluorescence enhancement, the molecules were separated by using such 3D substrates, and the mean distance between the molecules and nanoparticles' surface can be easily controlled by changing the diameters of the PAA tube. It was found that the PAA tube with smaller size provides better fluorescence enhancement. Enhanced cross section, a new fluorescence enhanced factor, combined with the simulation of localized electromagnetic field enhancement was presented to understand the experimental results. PMID- 27406633 TI - Characteristics associated with the application of an ecological approach to preventing childhood obesity. AB - OBJECTIVE: Applying an ecological approach to childhood obesity prevention requires a new way of thinking and working for many community-based practitioners who are used to focusing on individual behaviour change. The present study investigated individual and organizational characteristics associated with the application of an ecological approach by practitioners 6 months post-training. DESIGN: Individual and organizational characteristics and outcomes of a 6-week online training course were assessed at pre-course, post-course and 6-month follow-up. The application of an ecological approach was measured by three outcomes (application of course content, implementation of an action plan and trying a different approach) and analysed using a generalized estimating equation model with a binomial distribution and logit link and linear mixed models. SETTING: An online course for participants in the USA and abroad. SUBJECTS: Public health nutrition and youth development educators and their community partners, and other community practitioners, who completed the course and all three surveys (n 240). RESULTS: One individual characteristic (networking utility) and three organizational characteristics (ecological approach within job scope, funding, course content applied to work) were positively and significantly associated with the application of an ecological approach (P<0.05). Individual characteristics that were negatively and significantly associated with the application of an ecological approach were being a registered dietitian and having >=16 years of work experience (P<0.05). CONCLUSIONS: Training of community practitioners and the scope and funding of their positions should explicitly emphasize the usefulness or utility of networking and the use of an ecological approach for preventing childhood obesity. PMID- 27406634 TI - Modeling the Relative Importance of Nutrient and Carbon Loads, Boundary Fluxes, and Sediment Fluxes on Gulf of Mexico Hypoxia. AB - The Louisiana continental shelf in the northern Gulf of Mexico experiences bottom water hypoxia in the summer. In this study, we applied a biogeochemical model that simulates dissolved oxygen concentrations on the shelf in response to varying riverine nutrient and organic carbon loads, boundary fluxes, and sediment fluxes. Five-year model simulations demonstrated that midsummer hypoxic areas were most sensitive to riverine nutrient loads and sediment oxygen demand from settled organic carbon. Hypoxic area predictions were also sensitive to nutrient and organic carbon fluxes from lateral boundaries. The predicted hypoxic area decreased with decreases in nutrient loads, but the extent of change was influenced by the method used to estimate model boundary concentrations. We demonstrated that modeling efforts to predict changes in hypoxic area on the continental shelf in relationship to changes in nutrients should include representative boundary nutrient and organic carbon concentrations and functions for estimating sediment oxygen demand that are linked to settled organic carbon derived from water-column primary production. On the basis of our model analyses using the most representative boundary concentrations, nutrient loads would need to be reduced by 69% to achieve the Gulf of Mexico Nutrient Task Force Action Plan target hypoxic area of 5000 km(2). PMID- 27406635 TI - The Effect of Educational Software, Video Modelling and Group Discussion on Social-Skill Acquisition Among Students with Mild Intellectual Disabilities. AB - BACKGROUND: People with intellectual and developmental disabilities (IDD) often demonstrate difficulties in social skills. The purpose of this study was to examine the effects of a comprehensive intervention program on the acquisition of social skills among students with mild IDD. METHOD: Single subject multiple baseline design across situations was used for teaching five school-age children with mild IDD social skills embedded in school-based situations. RESULTS: Results demonstrate that the intervention program that included video modelling and games embedded with group discussions and simulations increased the level and use of adequate social behaviours within the school's natural environment. CONCLUSIONS: Results demonstrate the unique attribution of a comprehensive interactive program for acquisition and transfer of participants' social skills such as language pragmatics and social rules within the school environment. Group discussions and simulations were beneficial and enabled both group and personalized instruction through the unique application of the program designed for the study. PMID- 27406636 TI - Correction: Describing team development within a novel GP-led urgent care centre model: a qualitative study. PMID- 27406637 TI - Plea for routinely presenting prediction intervals in meta-analysis. AB - OBJECTIVES: Evaluating the variation in the strength of the effect across studies is a key feature of meta-analyses. This variability is reflected by measures like tau(2) or I(2), but their clinical interpretation is not straightforward. A prediction interval is less complicated: it presents the expected range of true effects in similar studies. We aimed to show the advantages of having the prediction interval routinely reported in meta-analyses. DESIGN: We show how the prediction interval can help understand the uncertainty about whether an intervention works or not. To evaluate the implications of using this interval to interpret the results, we selected the first meta-analysis per intervention review of the Cochrane Database of Systematic Reviews Issues 2009-2013 with a dichotomous (n=2009) or continuous (n=1254) outcome, and generated 95% prediction intervals for them. RESULTS: In 72.4% of 479 statistically significant (random effects p<0.05) meta-analyses in the Cochrane Database 2009-2013 with heterogeneity (I(2)>0), the 95% prediction interval suggested that the intervention effect could be null or even be in the opposite direction. In 20.3% of those 479 meta-analyses, the prediction interval showed that the effect could be completely opposite to the point estimate of the meta-analysis. We demonstrate also how the prediction interval can be used to calculate the probability that a new trial will show a negative effect and to improve the calculations of the power of a new trial. CONCLUSIONS: The prediction interval reflects the variation in treatment effects over different settings, including what effect is to be expected in future patients, such as the patients that a clinician is interested to treat. Prediction intervals should be routinely reported to allow more informative inferences in meta-analyses. PMID- 27406638 TI - Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol. AB - INTRODUCTION: No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study. METHODS: A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity. ETHICS AND DISSEMINATION: The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13). TRIAL REGISTRATION NUMBERS: PACTR201311000621110 and DOH 27-0614-4728; Pre-results. PMID- 27406639 TI - Complementary therapies for labour and birth study: a randomised controlled trial of antenatal integrative medicine for pain management in labour. AB - OBJECTIVE: To evaluate the effect of an antenatal integrative medicine education programme in addition to usual care for nulliparous women on intrapartum epidural use. DESIGN: Open-label, assessor blind, randomised controlled trial. SETTING: 2 public hospitals in Sydney, Australia. POPULATION: 176 nulliparous women with low risk pregnancies, attending hospital-based antenatal clinics. METHODS AND INTERVENTION: The Complementary Therapies for Labour and Birth protocol, based on the She Births and acupressure for labour and birth courses, incorporated 6 evidence-based complementary medicine techniques: acupressure, visualisation and relaxation, breathing, massage, yoga techniques, and facilitated partner support. Randomisation occurred at 24-36 weeks' gestation, and participants attended a 2 day antenatal education programme plus standard care, or standard care alone. MAIN OUTCOME MEASURES: Rate of analgesic epidural use. Secondary: onset of labour, augmentation, mode of birth, newborn outcomes. RESULTS: There was a significant difference in epidural use between the 2 groups: study group (23.9%) standard care (68.7%; risk ratio (RR) 0.37 (95% CI 0.25 to 0.55), p<=0.001). The study group participants reported a reduced rate of augmentation (RR=0.54 (95% CI 0.38 to 0.77), p<0.0001); caesarean section (RR=0.52 (95% CI 0.31 to 0.87), p=0.017); length of second stage (mean difference=-0.32 (95% CI -0.64 to 0.002), p=0.05); any perineal trauma (0.88 (95% CI 0.78 to 0.98), p=0.02) and resuscitation of the newborn (RR=0.47 (95% CI 0.25 to 0.87), p<=0.015). There were no statistically significant differences found in spontaneous onset of labour, pethidine use, rate of postpartum haemorrhage, major perineal trauma (third and fourth degree tears/episiotomy), or admission to special care nursery/neonatal intensive care unit (p=0.25). CONCLUSIONS: The Complementary Therapies for Labour and Birth study protocol significantly reduced epidural use and caesarean section. This study provides evidence for integrative medicine as an effective adjunct to antenatal education, and contributes to the body of best practice evidence. TRIAL REGISTRATION NUMBER: ACTRN12611001126909. PMID- 27406641 TI - Healthcare professional and patient codesign and validation of a mechanism for service users to feedback patient safety experiences following a care transfer: a qualitative study. AB - OBJECTIVE: To develop and validate a mechanism for patients to provide feedback on safety experiences following a care transfer between organisations. DESIGN: Qualitative study using participatory methods (codesign workshops) and cognitive interviews. Workshop data were analysed concurrently with participants, and cognitive interviews were thematically analysed using a deductive approach based on the developed feedback mechanism. PARTICIPANTS: Expert patients (n=5) and healthcare professionals (n=11) were recruited purposively to develop the feedback mechanism in 2 workshops. Workshop 1 explored principles underpinning safety feedback mechanisms, and workshop 2 included the practical development of the feedback mechanism. Final design and content of the feedback mechanism (a safety survey) were verified by workshop participants, and cognitive interviews (n=28) were conducted with patients. RESULTS: Workshop participants identified that safety feedback mechanisms should be patient-centred, short and concise with clear signposting on how to complete, with an option to be anonymous and balanced between positive (safe) and negative (unsafe) experiences. The agreed feedback mechanism consisted of a survey split across 3 stages of the care transfer: departure, journey and arrival. Care across organisational boundaries was recognised as being complex, with healthcare professionals acknowledging the difficulty implementing changes that impact other organisations. Cognitive interview participants agreed the content of the survey was relevant but identified barriers to completion relating to the survey formatting and understanding of a care transfer. CONCLUSIONS: Participatory, codesign principles helped overcome differences in understandings of safety in the complex setting of care transfers when developing a safety survey. Practical barriers to the survey's usability and acceptability to patients were identified, resulting in a modified survey design. Further research is required to determine the usability and acceptability of the survey to patients and healthcare professionals, as well as identifying how governance structures should accommodate patient feedback when relating to multiple health or social care providers. PMID- 27406640 TI - Incidence of adverse drug events in public and private hospitals in Riyadh, Saudi Arabia: the (ADESA) prospective cohort study. AB - OBJECTIVES: To determine the incidence of adverse drug events (ADEs) and assess their severity and preventability in four Saudi hospitals. DESIGN: Prospective cohort study. SETTING: The study included patients admitted to medical, surgical and intensive care units (ICUs) of four hospitals in Saudi Arabia. These hospitals include a 900-bed tertiary teaching hospital, a 400-bed private hospital, a 1400-bed large government hospital and a 350-bed small government hospital. PARTICIPANTS: All patients (>=12 years) admitted to the study units over 4 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidents were collected by pharmacists and reviewed by independent clinicians. Reviewers classified the identified incidents as ADEs, potential ADEs (PADEs) or medication errors and then determined their severity and preventability. RESULTS: We followed 4041 patients from admission to discharge. Of these, 3985 patients had complete data for analysis. The mean+/-SD age of patients in the analysed cohort was 43.4+/ 19.0 years. A total of 1676 ADEs were identified by pharmacists during the medical chart review. Clinician reviewers accepted 1531 (91.4%) of the incidents identified by the pharmacists (245 ADEs, 677 PADEs and 609 medication errors with low risk of causing harm). The incidence of ADEs was 6.1 (95% CI 5.4 to 6.9) per 100 admissions and 7.9 (95% CI 6.9 to 8.9) per 1000 patient-days. The occurrence of ADEs was most common in ICUs (149 (60.8%)) followed by medical (67 (27.3%)) and surgical (29 (11.8%)) units. In terms of severity, 129 (52.7%) of the ADEs were significant, 91 (37.1%) were serious, 22 (9%) were life-threatening and three (1.2%) were fatal. CONCLUSIONS: We found that ADEs were common in Saudi hospitals, especially in ICUs, causing significant morbidity and mortality. Future studies should focus on investigating the root causes of ADEs at the prescribing stage, and development and testing of interventions to minimise harm from medications. PMID- 27406643 TI - Intra-articular bupivacaine after joint arthroplasty: a systematic review and meta-analysis of randomised placebo-controlled studies. AB - OBJECTIVES: To evaluate the efficacy and safety of intra-articular (IA) bupivacaine administered for pain relief after joint arthroplasty. DESIGN: Meta analysis. METHODS: A systematic review was conducted to identify the randomised controlled trials using IA bupivacaine for postoperative pain relief from MEDLINE, Cochrane Library and EMBASE databases (up to October 2015). The standardised mean difference (SMD), the relative risk (RR) and their corresponding 95% CIs were calculated using the RevMan statistical software. RESULTS: A total of 11 randomised controlled trials were included. Statistically significant differences between IA bupivacaine and placebo were observed for the mean visual analogue scale (VAS) values (SMD -0.55; 95% CI -0.89 to -0.22; p<0.001) and narcotic consumption (SMD -0.32; 95% CI -0.55 to -0.08; p=0.008) during the period of 24 hours postoperatively and narcotic consumption during the period between 24 and 48 hours postoperatively (SMD -0.32; 95% CI -0.55 to -0.08; p=0.009). However, there was no significant difference in the mean VAS pain score during the period between 24 and 48 hours postoperatively (SMD -0.09, 95% CI 0.30 to 0.11; p=0.37) and in the incidence of adverse effects 24-72 hours postoperatively (RR 0.97; 95% CI 0.60 to 1.57; p=0.91). CONCLUSIONS: The administration of IA bupivacaine after joint arthroplasty is effective for pain relief without increasing adverse effects. PMID- 27406642 TI - Screening for cognitive impairment with the Montreal Cognitive Assessment in Chinese patients with acute mild stroke and transient ischaemic attack: a validation study. AB - OBJECTIVE: We aimed to establish the cut-off point of the Montreal Cognitive Assessment (MoCA-Beijing) in screening for cognitive impairment (CI) within 2 weeks of mild stroke or transient ischaemic attack (TIA). METHODS: A total of 80 acute mild ischaemic stroke patients and 22 TIA patients were recruited. They received the MoCA-Beijing and a formal neuropsychological test battery. CI was defined by 1.5 SD below the established norms on a formal neuropsychological test battery. RESULTS: Most stroke and TIA patients were in their 50s (53.95+/-11.43 years old), with greater than primary school level of education. The optimal cut off point for MoCA-Beijing in discriminating patients with CI from those with no cognitive impairment (NCI) was 22/23 (sensitivity 85%, specificity 88%, positive predictive value=91%, negative predictive value=80%, classification accuracy=86%). The predominant cognitive deficits were characteristic of frontal subcortical impairment, such as visuomotor speed (46.08%), attention/executive function (42.16%) and visuospatial ability (40.20%). CONCLUSIONS: A MoCA-Beijing cut-off score of 22/23 is optimally sensitive and specific for detecting CI after mild stroke, and TIA in the acute stroke phase, and is recommended for routine clinical practice. PMID- 27406644 TI - Prostate-specific antigen testing in inner London general practices: are those at higher risk most likely to get tested? AB - OBJECTIVES: To investigate the association between factors influencing prostate specific antigen (PSA) testing prevalence including prostate cancer risk factors (age, ethnicity, obesity) and non-risk factors (social deprivation and comorbidity). SETTING: A cross-sectional database of 136 inner London general practices from 1 August 2009 to 31 July 2014. PARTICIPANTS: Men aged >=40 years without prostate cancer were included (n=150 481). PRIMARY OUTCOME: Logistic regression analyses were used to estimate the association between PSA testing and age, ethnicity, social deprivation, body mass index (BMI) and comorbidity while adjusting for age, benign prostatic hypertrophy, prostatitis and tamsulosin or finasteride use. RESULTS: PSA testing prevalence was 8.2% (2013-2014), and the mean age was 54 years (SD 11). PSA testing was positively associated with age (OR 70-74 years compared to 40-44 years: 7.34 (95% CI 6.82 to 7.90)), ethnicity (black) (OR compared to white: 1.78 (95% CI 1.71 to 1.85)), increasing BMI and cardiovascular comorbidity. Testing was negatively associated with Chinese ethnicity and with increasing social deprivation. CONCLUSIONS: PSA testing among black patients was higher compared to that among white patients, which differs from lower testing rates seen in previous studies. PSA testing was positively associated with prostate cancer risk factors and non-risk factors. Association with non-risk factors may increase the risk of unnecessary invasive diagnostic procedures. PMID- 27406645 TI - Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol. AB - INTRODUCTION: Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness. METHODS AND ANALYSIS: This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central-CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea-hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time. ETHICS AND DISSEMINATION: This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02273089; Pre-results. PMID- 27406646 TI - Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study. AB - OBJECTIVES: To investigate geographic variation in guideline-indicated treatments for non-ST-elevation myocardial infarction (NSTEMI) in the English National Health Service (NHS). DESIGN: Cohort study using registry data from the Myocardial Ischaemia National Audit Project. SETTING: All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS. PARTICIPANTS: 357 228 patients with NSTEMI between 1 January 2003 and 30 June 2013. MAIN OUTCOME MEASURE: Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication. RESULTS: The proportion of NSTEMI who received optimal care was low (48 257/357 228; 13.5%) and varied between CCGs (median 12.8%, IQR 0.7-18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0-40.0%) and least for use of an ECG (96.7%, 92.5-98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6-97.1%), and aspirin (90.1%, 85.1-93.3%) and statins (86.4%, 82.3-91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7-16.6%), dietary advice (32.4%, 23.9 41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4-46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between hospital differences (median 64.7%, IQR 57.4-70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 0.976 to 0.999). CONCLUSIONS: Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths. TRIAL REGISTRATION NUMBER: NCT02436187. PMID- 27406648 TI - Alkali metal ion induced cube shaped mesoporous hematite particles for improved magnetic properties and efficient degradation of water pollutants. AB - Mesoporous cube shaped hematite (alpha-Fe2O3) particles were prepared using FeCl3 as an Fe(3+) precursor and 1-butyl-3-methylimidazolium bromide (ionic liquid) as a soft template in the presence of different alkali metal (lithium, sodium and potassium) acetates, under hydrothermal conditions at 150 degrees C/4 h followed by calcination at 350 degrees C. The formation of the alpha-Fe2O3 phase in the synthesized samples was confirmed by XRD, FTIR and Raman spectroscopy. Unlike K(+) ions, intercalation of Li(+) and Na(+) ions occurred in alpha-Fe2O3 crystal layers as evidenced by XRD and Raman spectroscopy. Electron microscopy (FESEM and TEM) images showed the formation of cube-like particles of different sizes in the presence of Li(+), Na(+) and K(+) ions. The mesoporosity of the products was confirmed by N2 adsorption-desorption studies, while their optical properties were analyzed by UV-DRS. Na(+) ion intercalated alpha-Fe2O3 microcubes showed improved coercivity (5.7 kOe) due to increased strain in crystals, and shape and magnetocrystalline anisotropy. Temperature dependent magnetization of the samples confirmed the existence of Morin temperature in the range of 199-260 K. Catalytic degradation of methylene blue (MB), a toxic water pollutant, was studied using the synthesized products via a heterogeneous photo-Fenton process. The degradation products were traced by electrospray ionization-mass spectrometry (ESI-MS). The alpha-Fe2O3 microcubes obtained in the presence of Na(+) ions exhibited a more efficient degradation of MB to non-toxic open chain products. PMID- 27406647 TI - Mortality Reduction in Septic Shock by Plasma Adsorption (ROMPA): a protocol for a randomised clinical trial. AB - INTRODUCTION: There is a lack of evidence in the efficacy of the coupled plasma filtration adsorption (CPFA) to reduce the mortality rate in septic shock. To fill this gap, we have designed the ROMPA study (Mortality Reduction in Septic Shock by Plasma Adsorption) to confirm whether treatment with an adequate dose of treated plasma by CPFA could confer a clinical benefit. METHODS AND ANALYSIS: Our study is a multicentric randomised clinical trial with a 28-day and 90-day follow up and allocation ratio 1:1. Its aim is to clarify whether the application of high doses of CPFA (treated plasma >=0.20 L/kg/day) in the first 3 days after randomisation, in addition to the current clinical practice, is able to reduce hospital mortality in patients with septic shock in intensive care units (ICUs) at 28 and 90 days after initiation of the therapy. The study will be performed in 10 ICUs in the Southeast of Spain which follow the same protocol in this disease (based on the Surviving Sepsis Campaign). Our trial is designed to be able to demonstrate an absolute mortality reduction of 20% (alpha=0.05; 1-beta=0.8; n=190(95*2)). The severity of the process, ensuring the recruitment of patients with a high probability of death (50% in the control group), will be achieved through an adequate stratification by using both severity scores and classical definitions of severe sepsis/septic shock and dynamic parameters. Our centres are fully aware of the many pitfalls associated with previous medical device trials. Trying to reduce these problems, we have developed a training programme to improve the CPFA use (especially clotting problems). ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committees of all the participant centres. The findings of the trial will be disseminated through peer-reviewed journals, as well as national and international conference presentations. TRIAL REGISTRATION NUMBER: NCT02357433; Pre-results. PMID- 27406649 TI - Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women. AB - NEW FINDINGS: What is the central question of this study? Does a clinically relevant intravenous dose of erythropoeitin affect the hypoxic ventilatory response and/or hypoxic pulmonary vasoconstriction in healthy humans? What is the main finding and its importance? Erythropoeitin does not influence the ventilatory and pulmonary vascular responses to acute hypoxia in men or women. Sustained and chronic hypoxia lead to an increase in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical i.v. dose of recombinant human erythropoietin (50 IU kg 1 ) on the isocapnic HVR and HPV in seven male and seven female subjects by exposing them to hypoxia for 20 min (end-tidal PMID- 27406650 TI - Through rose-coloured glasses: An empirical test of narcissistic overestimation. AB - BACKGROUND: Grandiosity is designated as a hallmark trait of narcissism. The current study tested whether narcissistic traits are related to overestimation of a range of agentic performances. METHOD: Eighty-five non-patients executed six objective tasks to assess their level of (emotional) intelligence, first impression, attractiveness, social skills and learning performance. They were also asked to estimate their level of functioning in these six areas. This estimation was given on two moments: before and after performing the objective tasks. Our main variable of interest was the degree to which subjective estimation exceeds objective scores. RESULTS: Narcissistic traits were related to overestimation of (emotional) intelligence, attractiveness and social skills, particularly at a global level before performing the tasks. LIMITATIONS: The use of a homogenous student sample; Mainly agentic performances, were studied. CONCLUSION: Overall, the findings provide a theoretical validation of unwarranted feelings of grandiosity as a core narcissistic criterion. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27406651 TI - Diet adaptation in dog reflects spread of prehistoric agriculture. AB - Adaptations allowing dogs to thrive on a diet rich in starch, including a significant AMY2B copy number gain, constituted a crucial step in the evolution of the dog from the wolf. It is however not clear whether this change was associated with the initial domestication, or represents a secondary shift related to the subsequent development of agriculture. Previous efforts to study this process were based on geographically limited data sets and low-resolution methods, and it is therefore not known to what extent the diet adaptations are universal among dogs and whether there are regional differences associated with alternative human subsistence strategies. Here we use droplet PCR to investigate worldwide AMY2B copy number diversity among indigenous as well as breed dogs and wolves to elucidate how a change in dog diet was associated with the domestication process and subsequent shifts in human subsistence. We find that AMY2B copy numbers are bimodally distributed with high copy numbers (median 2nAMY2B=11) in a majority of dogs but no, or few, duplications (median 2nAMY2B=3) in a small group of dogs originating mostly in Australia and the Arctic. We show that this pattern correlates geographically to the spread of prehistoric agriculture and conclude that the diet change may not have been associated with initial domestication but rather the subsequent development and spread of agriculture to most, but not all regions of the globe. PMID- 27406653 TI - The impact of implementation of the requirements of Standard No. OHSAS 18001:2007 to reduce the number of injuries at work and financial costs in the Republic of Croatia. AB - This article contains the results of research into the impact of implementation of the requirements mentioned in Standard No. OHSAS 18001:2007 to reduce the number of injuries at work and the financial costs incurred in this way. The study was conducted on a determined sample by a written questionnaire survey method in the Republic of Croatia. The objective of the empirical research is to determine the impact of implementation of the requirements of Standard No. OHSAS 18001:2007 to reduce the number of injuries at work and financial costs in Croatia in business organizations that implement these requirements. To provide a broader picture, the research included the collection and analysis of data on the impact of the Standard No. OHSAS 18001:2007 on accidents and fatalities at work. Research findings are based on the analysis of performed statistical data where correlation and regression analysis has been applied. PMID- 27406652 TI - Spin texture of time-reversal symmetry invariant surface states on W(110). AB - We find in the case of W(110) previously overlooked anomalous surface states having their spin locked at right angle to their momentum using spin-resolved momentum microscopy. In addition to the well known Dirac-like surface state with Rashba spin texture near the -point, we observe a tilted Dirac cone with circularly shaped cross section and a Dirac crossing at 0.28 * within the projected bulk band gap of tungsten. This state has eye-catching similarities to the spin-locked surface state of a topological insulator. The experiments are fortified by a one-step photoemission calculation in its density-matrix formulation. PMID- 27406654 TI - Is vestibular rehabilitation effective in improving dizziness and function after unilateral peripheral vestibular hypofunction? An abridged version of a Cochrane Review. AB - INTRODUCTION: Unilateral peripheral vestibular dysfunction (UPVD) is characterized by complaints of dizziness, gaze disturbances and balance impairment. Current management includes medication, physical man oeuvres and exercise regimes, the latter known collectively as vestibular rehabilitation. The aim was to assess the effectiveness of vestibular rehabilitation in people with symptomatic UVPD. EVIDENCE ACQUISITION: A systematic review was conducted for the population of adults diagnosed with symptomatic UPVD, living in the community. We searched all relevant databases and trials registers to identify randomized controlled trials comparing vestibular rehabilitation versus control (e.g. placebo), other treatment (non-vestibular rehabilitation, e.g. pharmacological) or another form of vestibular rehabilitation. We considered possible effectiveness in the domains of symptoms (dizziness) or function (activities, quality of life) and where possible combined results in meta-analyses to provide overall estimates of effect. EVIDENCE SYNTHESIS: We included 39 studies involving 2441 participants with UPVD in the review. Individual and pooled analyses of the primary outcome (frequency of dizziness) showed a statistically significant effect in favor of vestibular rehabilitation over control or no intervention (odds ratio (OR) 2.67, 95% confidence interval (CI) 1.85 to 3.86). Secondary outcomes measures related to levels of activity or participation showed a strong trend towards significant differences between the groups (standardized mean difference -0.83, 95% CI -1.02 to -0.64). However when movement-based vestibular rehabilitation was compared to physical maneuvers for benign paroxysmal positional vertigo (BPPV), where the latter was shown to be superior in cure rate in the short term (OR 0.19, 95% CI 0.07 to 0.49). There were no reported adverse effects and risk of bias was generally low across the studies. CONCLUSIONS: There is moderate to strong evidence that vestibular rehabilitation is a safe, effective management for UPVD. For the specific diagnostic group of BPPV, physical (repositioning) maneuvers are more effective in the short term than exercise-based vestibular rehabilitation; although a combination of the two is effective for longer-term functional recovery. There is insufficient evidence to discriminate between differing forms of vestibular rehabilitation. PMID- 27406656 TI - Pyrene boronic acid cyclic ester: a new fast self-recovering mechanoluminescent material at room temperature. AB - Two pyrene boronic acid cyclic esters, PPB and NPB, were prepared and their solid state fluorescence properties were investigated. Interestingly, the results showed that PPB with a 5-membered ring possessed reversible mechanoluminescence and vapochromic behaviour with a fast self-recovering ability at room temperature, whereas NPB with a 6-membered ring did not. It was demonstrated that the mechanically responsive fluorescence properties of PPB and NPB were highly related to the molecular packing mode and the solid state plasticity. PMID- 27406657 TI - Introduction to Special Issue: Towards Ecologically Valid Protocols for the Assessment of Hearing and Hearing Devices. PMID- 27406655 TI - Time for a Consensus Conference on pain in neurorehabilitation. PMID- 27406658 TI - Theoretical Issues of Validity in the Measurement of Aided Speech Reception Threshold in Noise for Comparing Nonlinear Hearing Aid Systems. AB - BACKGROUND: Adaptive Speech Reception Threshold in noise (SRTn) measurements are often used to make comparisons between alternative hearing aid (HA) systems. Such measurements usually do not constrain the signal-to-noise ratio (SNR) at which testing takes place. Meanwhile, HA systems increasingly include nonlinear features that operate differently in different SNRs, and listeners differ in their inherent SNR requirements. PURPOSE: To show that SRTn measurements, as commonly used in comparisons of alternative HA systems, suffer from threats to their validity, to illustrate these threats with examples of potentially invalid conclusions in the research literature, and to propose ways to tackle these threats. RESEARCH DESIGN: An examination of the nature of SRTn measurements in the context of test theory, modern nonlinear HAs, and listener diversity. STUDY SAMPLE, DATA COLLECTION, AND ANALYSIS: Examples from the audiological research literature were used to estimate typical interparticipant variation in SRTn and to illustrate cases where validity may have been compromised. RESULTS AND CONCLUSIONS: There can be no doubt that SRTn measurements, when used to compare nonlinear HA systems, in principle, suffer from threats to their internal and external/ecological validity. Interactions between HA nonlinearities and SNR, and interparticipant differences in inherent SNR requirements, can act to generate misleading results. In addition, SRTn may lie at an SNR outside the range for which the HA system is designed or expected to operate in. Although the extent of invalid conclusions in the literature is difficult to evaluate, examples of studies were nevertheless identified where the risk of each form of invalidity is significant. Reliable data on ecological SNRs is becoming available, so that ecological validity can be assessed. Methodological developments that can reduce the risk of invalid conclusions include variations on the SRTn measurement procedure itself, manipulations of stimulus or scoring conditions to place SRTn in an ecologically relevant range, and design and analysis approaches that take account of interparticipant differences. PMID- 27406659 TI - A Dynamic Speech Comprehension Test for Assessing Real-World Listening Ability. AB - BACKGROUND: Many listeners with hearing loss report particular difficulties with multitalker communication situations, but these difficulties are not well predicted using current clinical and laboratory assessment tools. PURPOSE: The overall aim of this work is to create new speech tests that capture key aspects of multitalker communication situations and ultimately provide better predictions of real-world communication abilities and the effect of hearing aids. RESEARCH DESIGN: A test of ongoing speech comprehension introduced previously was extended to include naturalistic conversations between multiple talkers as targets, and a reverberant background environment containing competing conversations. In this article, we describe the development of this test and present a validation study. STUDY SAMPLE: Thirty listeners with normal hearing participated in this study. DATA COLLECTION AND ANALYSIS: Speech comprehension was measured for one-, two-, and three-talker passages at three different signal-to-noise ratios (SNRs), and working memory ability was measured using the reading span test. Analyses were conducted to examine passage equivalence, learning effects, and test-retest reliability, and to characterize the effects of number of talkers and SNR. RESULTS: Although we observed differences in difficulty across passages, it was possible to group the passages into four equivalent sets. Using this grouping, we achieved good test-retest reliability and observed no significant learning effects. Comprehension performance was sensitive to the SNR but did not decrease as the number of talkers increased. Individual performance showed associations with age and reading span score. CONCLUSIONS: This new dynamic speech comprehension test appears to be valid and suitable for experimental purposes. Further work will explore its utility as a tool for predicting real-world communication ability and hearing aid benefit. PMID- 27406660 TI - Common Sound Scenarios: A Context-Driven Categorization of Everyday Sound Environments for Application in Hearing-Device Research. AB - BACKGROUND: Evaluation of hearing-device signal-processing features is performed for research and development purposes, but also in clinical settings. Most people agree that the benefit experienced in a hearing-device user's daily life is most important, but laboratory tests are popular since they can be performed uniformly for all participants in a study using sensitive outcome measures. In order to design laboratory tests that have the potential of indicating real-life benefit, there is a need for more information about the acoustic environments and listening situations encountered by hearing-device users as well as by normal hearing people. PURPOSE: To investigate the acoustic environments and listening situations people encounter, and to provide a structured framework of common sound scenarios (CoSS) that can be used for instance when designing realistic laboratory tests. RESEARCH DESIGN: A literature search was conducted. Extracted acoustic environments and listening situations were categorized using a context based approach. A set of common sound scenarios was established based on the findings from the literature. DATA COLLECTION: A number of publications providing data on encountered acoustic environments and listening situations were identified. Focus was on studies including informants who reported or recorded information in field trials. Nine relevant references were found. In combination with data collected at our laboratory, 187 examples of acoustic environments or listening situations were found. RESULTS: Based on the extracted data, a categorization approach based on context (intentions and tasks) was used when creating CoSS. Three intention categories, "speech communication," "focused listening," and "nonspecific" were divided into seven task categories. In each task category, two sound scenarios were described, creating in total 14 common sound scenarios. The literature search showed a general lack of studies investigating acoustic environments and listening situations, in particular studies where normal-hearing informants are included and studies performed outside North America and Western Europe. CONCLUSIONS: A structured framework was developed. Intentions and tasks constitute the main categories in the framework, and 14 common sound scenarios were selected and described. The framework can for instance be used when developing hearing-device signal-processing features, in the evaluation of such features in realistic laboratory tests, and for demonstration of feature effects to hearing-device wearers. PMID- 27406661 TI - Evaluation of Loudspeaker-Based Virtual Sound Environments for Testing Directional Hearing Aids. AB - BACKGROUND: Assessments of hearing aid (HA) benefits in the laboratory often do not accurately reflect real-life experience. This may be improved by employing loudspeaker-based virtual sound environments (VSEs) that provide more realistic acoustic scenarios. It is unclear how far the limited accuracy of these VSEs influences measures of subjective performance. PURPOSE: Verify two common methods for creating VSEs that are to be used for assessing HA outcomes. RESEARCH DESIGN: A cocktail-party scene was created inside a meeting room and then reproduced with a 41-channel loudspeaker array inside an anechoic chamber. The reproduced scenes were created either by using room acoustic modeling techniques or microphone array recordings. STUDY SAMPLE: Participants were 18 listeners with a symmetrical, sloping, mild-to-moderate hearing loss, aged between 66 and 78 yr (mean = 73.8 yr). DATA COLLECTION AND ANALYSIS: The accuracy of the two VSEs was assessed by comparing the subjective performance measured with two-directional HA algorithms inside all three acoustic environments. The performance was evaluated by using a speech intelligibility test and an acceptable noise level task. RESULTS: The general behavior of the subjective performance seen in the real environment was preserved in the two VSEs for both directional HA algorithms. However, the estimated directional benefits were slightly reduced in the model based VSE, and further reduced in the recording-based VSE. CONCLUSIONS: It can be concluded that the considered VSEs can be used for testing directional HAs, but the provided sensitivity is reduced when compared to a real environment. This can result in an underestimation of the provided directional benefit. However, this minor limitation may be easily outweighed by the high realism of the acoustic scenes that these VSEs can generate, which may result in HA outcome measures with a significantly higher ecological relevance than provided by measures commonly performed in the laboratory or clinic. PMID- 27406662 TI - Spatial Acoustic Scenarios in Multichannel Loudspeaker Systems for Hearing Aid Evaluation. AB - BACKGROUND: Field tests and guided walks in real environments show that the benefit from hearing aid (HA) signal processing in real-life situations is typically lower than the predicted benefit found in laboratory studies. This suggests that laboratory test outcome measures are poor predictors of real-life HA benefits. However, a systematic evaluation of algorithms in the field is difficult due to the lack of reproducibility and control of the test conditions. Virtual acoustic environments that simulate real-life situations may allow for a systematic and reproducible evaluation of HAs under more realistic conditions, thus providing a better estimate of real-life benefit than established laboratory tests. PURPOSE: To quantify the difference in HA performance between a laboratory condition and more realistic conditions based on technical performance measures using virtual acoustic environments, and to identify the factors affecting HA performance across the tested environments. RESEARCH DESIGN: A set of typical HA beamformer algorithms was evaluated in virtual acoustic environments of different complexity. Performance was assessed based on established technical performance measures, including perceptual model predictions of speech quality and speech intelligibility. Virtual acoustic environments ranged from a simple static reference condition to more realistic complex scenes with dynamically moving sound objects. RESULTS: HA benefit, as predicted by signal-to-noise ratio (SNR) and speech intelligibility measures, differs between the reference condition and more realistic conditions for the tested beamformer algorithms. Other performance measures, such as speech quality or binaural degree of diffusiveness, do not show pronounced differences. However, a decreased speech quality was found in specific conditions. A correlation analysis showed a significant correlation between room acoustic parameters of the sound field and HA performance. The SNR improvement in the reference condition was found to be a poor predictor of HA performance in terms of speech intelligibility improvement in the more realistic conditions. CONCLUSIONS: Using several virtual acoustic environments of different complexity, a systematic difference in HA performance between a simple reference condition and more realistic environments was found, which may be related to the discrepancy between laboratory and real-life HA performance reported previously. PMID- 27406663 TI - Effects of Hearing Loss on Dual-Task Performance in an Audiovisual Virtual Reality Simulation of Listening While Walking. AB - BACKGROUND: Most activities of daily living require the dynamic integration of sights, sounds, and movements as people navigate complex environments. Nevertheless, little is known about the effects of hearing loss (HL) or hearing aid (HA) use on listening during multitasking challenges. PURPOSE: The objective of the current study was to investigate the effect of age-related hearing loss (ARHL) on word recognition accuracy in a dual-task experiment. Virtual reality (VR) technologies in a specialized laboratory (Challenging Environment Assessment Laboratory) were used to produce a controlled and safe simulated environment for listening while walking. RESEARCH DESIGN: In a simulation of a downtown street intersection, participants completed two single-task conditions, listening-only (standing stationary) and walking-only (walking on a treadmill to cross the simulated intersection with no speech presented), and a dual-task condition (listening while walking). For the listening task, they were required to recognize words spoken by a target talker when there was a competing talker. For some blocks of trials, the target talker was always located at 0 degrees azimuth (100% probability condition); for other blocks, the target talker was more likely (60% of trials) to be located at the center (0 degrees azimuth) and less likely (40% of trials) to be located at the left (270 degrees azimuth). STUDY SAMPLE: The participants were eight older adults with bilateral HL (mean age = 73.3 yr, standard deviation [SD] = 8.4; three males) who wore their own HAs during testing and eight controls with normal hearing (NH) thresholds (mean age = 69.9 yr, SD = 5.4; two males). No participant had clinically significant visual, cognitive, or mobility impairments. DATA COLLECTION AND ANALYSIS: Word recognition accuracy and kinematic parameters (head and trunk angles, step width and length, stride time, cadence) were analyzed using mixed factorial analysis of variances with group as a between-subjects factor. Task condition (single versus dual) and probability (100% versus 60%) were within-subject factors. In analyses of the 60% listening condition, spatial expectation (likely versus unlikely) was a within-subject factor. Differences between groups in age and baseline measures of hearing, mobility, and cognition were tested using t tests. RESULTS: The NH group had significantly better word recognition accuracy than the HL group. Both groups performed better when the probability was higher and the target location more likely. For word recognition, dual-task costs for the HL group did not depend on condition, whereas the NH group demonstrated a surprising dual-task benefit in conditions with lower probability or spatial expectation. For the kinematic parameters, both groups demonstrated a more upright and less variable head position and more variable trunk position during dual-task conditions compared to the walking-only condition, suggesting that safe walking was prioritized. The HL group demonstrated more overall stride time variability than the NH group. CONCLUSIONS: This study provides new knowledge about the effects of ARHL, HA use, and aging on word recognition when individuals also perform a mobility-related task that is typically experienced in everyday life. This research may help inform the development of more effective function-based approaches to assessment and intervention for people who are hard-of-hearing. PMID- 27406665 TI - A Method for Assessing Auditory Spatial Analysis in Reverberant Multitalker Environments. AB - BACKGROUND: Deficits in spatial hearing can have a negative impact on listeners' ability to orient in their environment and follow conversations in noisy backgrounds and may exacerbate the experience of hearing loss as a handicap. However, there are no good tools available for reliably capturing the spatial hearing abilities of listeners in complex acoustic environments containing multiple sounds of interest. PURPOSE: The purpose of this study was to explore a new method to measure auditory spatial analysis in a reverberant multitalker scenario. RESEARCH DESIGN: This study was a descriptive case control study. STUDY SAMPLE: Ten listeners with normal hearing (NH) aged 20-31 yr and 16 listeners with hearing impairment (HI) aged 52-85 yr participated in the study. The latter group had symmetrical sensorineural hearing losses with a four-frequency average hearing loss of 29.7 dB HL. DATA COLLECTION AND ANALYSIS: A large reverberant room was simulated using a loudspeaker array in an anechoic chamber. In this simulated room, 96 scenes comprising between one and six concurrent talkers at different locations were generated. Listeners were presented with 45-sec samples of each scene, and were required to count, locate, and identify the gender of all talkers, using a graphical user interface on an iPad. Performance was evaluated in terms of correctly counting the sources and accuracy in localizing their direction. RESULTS: Listeners with NH were able to reliably analyze scenes with up to four simultaneous talkers, while most listeners with hearing loss demonstrated errors even with two talkers at a time. Localization performance decreased in both groups with increasing number of talkers and was significantly poorer in listeners with HI. Overall performance was significantly correlated with hearing loss. CONCLUSIONS: This new method appears to be useful for estimating spatial abilities in realistic multitalker scenes. The method is sensitive to the number of sources in the scene, and to effects of sensorineural hearing loss. Further work will be needed to compare this method to more traditional single-source localization tests. PMID- 27406664 TI - The Effects of Hearing Impairment, Age, and Hearing Aids on the Use of Self Motion for Determining Front/Back Location. AB - BACKGROUND: There are two cues that listeners use to disambiguate the front/back location of a sound source: high-frequency spectral cues associated with the head and pinnae, and self-motion-related binaural cues. The use of these cues can be compromised in listeners with hearing impairment and users of hearing aids. PURPOSE: To determine how age, hearing impairment, and the use of hearing aids affect a listener's ability to determine front from back based on both self motion and spectral cues. RESEARCH DESIGN: We used a previously published front/back illusion: signals whose physical source location is rotated around the head at twice the angular rate of the listener's head movements are perceptually located in the opposite hemifield from where they physically are. In normal hearing listeners, the strength of this illusion decreases as a function of low pass filter cutoff frequency, this is the result of a conflict between spectral cues and dynamic binaural cues for sound source location. The illusion was used as an assay of self-motion processing in listeners with hearing impairment and users of hearing aids. STUDY SAMPLE: We recruited 40 hearing-impaired participants, with an average age of 62 yr. The data for three listeners were discarded because they did not move their heads enough during the experiment. DATA COLLECTION AND ANALYSIS: Listeners sat at the center of a ring of 24 loudspeakers, turned their heads back and forth, and used a wireless keypad to report the front/back location of statically presented signals and of dynamically moving signals with illusory locations. Front/back accuracy for static signals, the strength of front/back illusions, and minimum audible movement angle were measured for each listener in each condition. All measurements were made in each listener both aided and unaided. RESULTS: Hearing-impaired listeners were less accurate at front/back discrimination for both static and illusory conditions. Neither static nor illusory conditions were affected by high-frequency content. Hearing aids had heterogeneous effects from listener to listener, but independent of other factors, on average, listeners wearing aids exhibited a spectrally dependent increase in "front" responses: the more high-frequency energy in the signal, the more likely they were to report it as coming from the front. CONCLUSIONS: Hearing impairment was associated with a decrease in the accuracy of self-motion processing for both static and moving signals. Hearing aids may not always reproduce dynamic self-motion-related cues with sufficient fidelity to allow reliable front/back discrimination. PMID- 27406667 TI - Lipoxygenase and oxidative damage in cold-stressed maize. PMID- 27406668 TI - Inhibition of the pyridine nucleotide-linked mitochondrial Ca(2+) release by 4 hydroxynonenal: the role of thiolate-disulfide conversion. AB - Rat liver mitochondria contain a specific Ca(2+) release pathway which operates when intramitochondrial NAD(+) is hydrolyzed to ADPribose and nicotinamide. The molecular details of this pathway are incompletely understood. It has been reported that NAD(+) hydrolysis and therefore Ca(2+) release stimulated by t butylhydroperoxide is prevented by 4-hydroxynonenal (HNE). The reason underlying inhibition by HNE, however, remained unclear. It has also been reported that NAD(+) hydrolysis and Ca(2+) release are stimulated when some vicinal thiols are cross-linked, as shown with phenylarsine oxide or gliotoxin (GT). We now show that HNE also prevents the GT-induced Ca(2+) release, but only when given before GT. Conversely, GT stimulates Ca(2+) release only when given before HNE. Inhibition of Ca(2+) release by HNE is reduced by its preincubation with thiol compounds, the effectiveness of which increases with decreasing pKa of their sulfhydryl group. Preincubation of HNE with glutathione at high, but not at low, pH similarly reduces inhibition of Ca(2+) release by HNE. These findings provide evidence that HNE inhibition of Ca(2+) release is due to a modification of mitochondrial thiolates in a way that their cross-linking is prevented, and give further insight into the regulation of Ca(2+) release from intact mitochondria. PMID- 27406669 TI - Mechanisms of antioxidant activities of quercetin and catechin. PMID- 27406670 TI - Apparent superoxide dismutase-like activity of immunoglobulin. AB - Using various superoxide generating systems and nitroblue tetrazolium or cytochrome c as superoxide detector molecules it is possible to assess the superoxide dismutase activity of proteins. Intact antibodies raised to different antigens, the Fab' fragment of anti-TNF [M632] and well-characterized recombinant Fv fragments of the murine antibody NQ11.7.22 appear to possess superoxide dismutase (SOD)-like activity. Kinetic characteristics of the SOD-like activity of NQ11.7.22-Fv fragments suggest an enzymatic property and these fragments behave in an analogous manner to human erythrocyte Cu-Zn SOD. Furthermore, the SOD-like activity of the NQ11.7.22-Fv fragment is affected by certain single point mutations in the amino acid composition and has a pH optimum of 6.2-6.6 which is unlike Cu-Zn SOD (pH 7.8-8.2). A change in tyrosine at the 32 position in the heavy chain and histidine at position 27 of the light chain of the NQ11.7.22-Fv fragment results in a profound reduction in SOD-like activity. Tyrosine at the 32 position in the heavy chain is known to play a significant role in antigen binding suggesting that the SOD-like activity occurs at the antigen-binding site itself. Single-point mutations at the periphery of the antigen combining site on the NQ11.7.22-Fv fragment had little or no effect on SOD-like activity. Further studies show that immunoglobin (lgG-1), a commercially available murine monoclonal antibody, can also enhance the generation of hydrogen peroxide, the product of superoxide dismutation, when present in superoxide producing systems. The generation of hydrogen peroxide was increased by low pH (pH 6.25) with lgG-1 but reduced with Cu-Zn SOD. PMID- 27406671 TI - Insulin activation of NADH ferricyanide reductase in human erythrocytes is mediated by the insulin receptor tyrosine kinase: a comparative study in normal and diabetic states. AB - We have previously reported that NADH ferricyanide reductase in human erythrocytes is stimulated by insulin. Hormone-stimulated activities are attenuated in the presence of glycolytic inhibitors like vanadate, indicating the involvement of glycolysis in the mechanism by which insulin stimulates ferricyanide reduction. Activation of erythrocyte metabolism in response to insulin could be a result of hormone binding to its receptor, inducing phosphorylation of band 3 (at a site for reversible association of glycolytic enzymes) and/or other membrane proteins like the Na(+)/H(+) antiport. Activation of the antiporter protein by insulin can stimulate glycolysis by an increase in intracellular pH, an effect which is prevented by amiloride. Evidence for a role for tyrosine phosphorylation in triggering the reductase activation came from studies with protein kinase inhibitors. Genistein, sphingosine and acridine orange have been shown to prevent insulin-stimulated ferricyanide reduction, implicating tyrosine phosphorylation as an important signal for activation of the enzyme by insulin. To evaluate activation of the enzyme by insulin stimulated phosphorylation, a comparative study was done using erythrocytes from healthy and diabetic humans. We measured ferricyanide reductase activities in basal and insulin stimulated states. Basal activities were lower in diabetics than in normal humans. Nevertheless, hormone stimulated activities were similar, despite earlier reports of decreased receptor phosphorylation of exogenous substrates in type 2 diabetics. These observations, together with previous ones, suggest that insulin-receptor kinase interaction may mediate the action of insulin on human erythrocytes by phosphorylation of cellular proteins like band 3 and/or the Na(+)/H(+) antiport. PMID- 27406672 TI - Left ventricular interstitial 8-hydroxy-deoxyguanosine concentration following myocardial ischemia and reperfusion in anesthetized rats. AB - The effect of myocardial ischemia and reperfusion on left ventricular interstitial 8-hydroxydeoxyguanosine (8-OH-dG), a possible biomarker for in vivo oxidative deoxyribonucleic acid damage, in anesthetized rats was investigated. A microdialysis probe was implanted. Levels of 8-OH-dG in microdialysates were analyzed via an on-line high performance liquid chromatography system equipped with an electrochemical detector. Myocardial ischemia for 10 or 20 min, induced by clamping of the left anterior descending coronary artery, did not affect 8-OH dG levels. However, reperfusion following either 10-min or 20-min ischemia significantly increased 8-OH-dG levels in collected microdialysates. Reperfusion induced increases in 8-OH-dG levels were more prominent in the 20 min ischemia group (as high as 3.5 fold relative to basal levels) than in the 10 min ischemia group as high as 2.0 fold relative to basal levels). In conclusion, we observed that left ventricular interstitial 8-OH-dG concentration increased following myocardial ischemia and reperfusion in anesthetized rats. These results suggest that 8-OH-dG might be a useful biomarker for oxidative damage following myocardial ischemia and reperfusion. PMID- 27406673 TI - Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate mediated hepatic injury. AB - Glutathione (GSH) plays several important roles in the protection of cells against oxidative damage, particularly following exposure to xenobiotics. Ferric nitrilotriacetate (Fe-NTA) is a potent depletor of GSH and also enhances tissue lipid peroxidation. In this study, we show the effect of Fe-NTA treatment on hepatic GSH and some of the glutathione metabolizing enzymes, oxidant generation and liver damage. The level of hepatic GSH and the activities of glutathione reductase, glutathione S-transferase, glutathione peroxidase, and glucose 6 phosphate dehydrogenase all decrease following Fe-NTA administration. In these parameters the maximum decrease occurred at 12 h following Fe-NTA treatment. In contrast, gamma-glutamyl transpeptidase was increased at this time. Not surprisingly, the increase in the activity of gamma-glutamyl transpeptidase and decreases in GSH, glutathione peroxidase, glutathione reductase, glucose 6 phosphate dehydrogenase and glutathione S-transferase were found to be dependent on the dose of Fe-NTA administered. Fe-NTA administration also enhances the production of H2O2 and increases hepatic lipid peroxidation. Parallel to these changes, Fe-NTA enhances liver damage as evidenced by increases in serum transaminases. Once again, the liver damage is dependent on the dose of Fe-NTA and is maximal at 12 h. Pretreatment of animals with antioxidant, butylated hydroxy anisole (BHA), protects against Fe-NTA-mediated hepatotoxicity further supporting the involvement of oxidative stress in Fe-NTA-mediated hepatic damage. In aggregate, our results indicate that Fe-NTA administration eventuates in decreased hepatic GSH, a fall in the activities of glutathione metabolizing enzymes and excessive production of oxidants, all of which are involved in the cascade of events leading to iron-mediated hepatic injury. PMID- 27406674 TI - Free radical reactions involving the angiotensin converting enzyme inhibitor captopril. AB - Using the pulse radiolysis technique, absolute rate constants have been obtained for the reaction of captopril with several free radicals. The results demonstrate that although captopril reacts rapidly with a number of free radicals, such as the hydroxyl radical (k = 5.1 * 10(9) dm(-3)mol(-1)s(-1)) and the thiocyanate radical anion (k = 1.3 * 10(7) dm(-3)mol(-1)s(-1)), it is not exceptional in this ability. Similarly, the reactions with carbon centred radicals although rapid are an order of magnitude slower than those observed with glutathione. Additional lipid peroxidation studies further demonstrate that captopril is a much less effective antioxidant than glutathione. The data go some way to supporting the view that any attenuation of reperfusion injury by captopril is not through a direct free radical scavenging mechanism but may be afforded by other, non radical-mediated mechanisms. PMID- 27406675 TI - The crocin assay for the determination of relative rate constants of alkoxyl radical reactions with the pyridoindole stobadine and with other antioxidants. AB - The water-soluble carotenoid crocin is bleached in aqueous solutions by tert butyloxy radicals (t-BuO(.)) photolytically generated from tert-butyl hydroperoxide. Crocin bleaching as measured at 440 nm can be competitively inhibited by antioxidants. This method therefore allows the determination of the relative reaction rates of these compounds with the t-BuO(.) radicals. In this test system the scavenging effect of the pyridoindole stobadine, a new antioxidant with potential for the treatment of tissue injury caused by oxidative stress, was compared with other known antioxidants. Generally good agreement was observed in two different approaches for the evaluation of the experimental data. The relative rate constants of the antioxidants tested increased in the order: stobadine, chlorpromazine, isoascorbic acid, trolox, ascorbic acid. Since it has been shown previously that stobadine can scavenge alkoxyl radicals also in a non polar environment, this antioxidant property may be important in the inhibition of lipid peroxidation. PMID- 27406676 TI - The synthesis and use of a (15)N and (2)H isotopically-labelled derivative of the spin-trap 3, 5-dibromo-4-nitrosobenzenesulphonic acid. AB - We report the synthesis and use of d2-(15)N isotopically-labelled 3, 5-dibromo-4 nitrosobenzenesulphonic acid (DBNBS-d2-(15)N, as its sodium salt), a spin-trap possessing several advantages over non-labelled DBNBS. The simplification in the electron paramagnetic resonance spectra of radical adducts of DBNBS-d2-(15)N compared with those of DBNBS not only results in increased sensitivity, but also facilitates the assignment and analysis of complex spectra. An example of this simplification is given. PMID- 27406677 TI - Correspondence. PMID- 27406678 TI - Enhanced conversion efficiency in perovskite solar cells by effectively utilizing near infrared light. AB - Up-conversion beta-NaYF4:Yb(3+),Tm(3+)/NaYF4 core-shell nanoparticles (NYF NPs) with a high luminous intensity in the visible light region were synthesized by a hydrothermal reaction process. Photocurrent densities of the mesoscopic perovskite solar cells fabricated by incorporating up-conversion NYF NPs into the electron transporting layer are effectively enhanced. The effects of the thicknesses of the electron transporting layer and the weight ratio of up conversion NYF NPs/TiO2 on the power conversion efficiency (PCE) of the as fabricated devices were also investigated. The results indicate that the PCE of the optimized device achieves 16.9%, which is 20% higher than that of the device without introducing NYF NPs, and the steady-state PCE of the as-fabricated devices is close to its transient-state PCE. The up-conversion effect of NYF NPs is conducive to higher device performance rather than the nanoparticles as scattering centers to increase possible light absorption of the perovskite film or the electronic effect of the NaYF4 shell surface. These results can be further confirmed by finite-difference time-domain simulation. Photoluminescence results suggest that the multiphonon-assistance can accelerate the nonradiative recombination process at a lower temperature. Incorporating NYF NPs into the electron transporting layer opens a new approach to a promising family of electron transporting materials for mesoscopic perovskite solar cells. PMID- 27406679 TI - A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme metabolite coupling in breast cancer. AB - Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured. PMID- 27406680 TI - Low-Voltage Voltammetric Electrowetting of Graphite Surfaces by Ion Intercalation/Deintercalation. AB - We demonstrate low-voltage electrowetting at the surface of freshly cleaved highly oriented pyrolytic graphite (HOPG). Using cyclic voltammetry (CV), electrowetting of a droplet of a sodium perchlorate solution is observed at moderately positive potentials on high-quality (low step edge coverage) HOPG, leading to significant changes in the contact angle and relative contact diameter that are comparable to the results of the widely studied electrowetting on dielectric (EWOD) system, but over a much lower voltage range. The electrowetting behavior is found to be reasonably fast, reversible, and repeatable for at least 20 cyclic scans (maximum tested). In contrast to classical electrowetting, e.g., EWOD, the electrowetting of the droplet on HOPG occurs with the intercalation/deintercalation of anions between the graphene layers of graphite, driven by the applied potential, observed in the CV response, and detected by X ray photoelectron spectroscopy. The electrowetting behavior is strongly influenced by those factors that affect the extent of the intercalation/deintercalation of ions on graphite, such as potential range scan rate, potential polarity, quality of the HOPG substrate (step edge density and step height), and type of anion in the solution. In addition to perchlorate, sulfate salts also promote electrowetting, but some other salts do not. Our findings suggest a new mechanism for electrowetting based on ion intercalation, and the results are important to fundamental electrochemistry as well as to diversifying the means by which electrowetting can be controlled and applied. PMID- 27406681 TI - Patient-specific hemodynamics and stress-strain state of cerebral aneurysms. AB - PURPOSE: Approximately 5% of the adult population has one or more cerebral aneurysm. Aneurysms are one of the most dangerous cerebral vascular pathologies. Aneurysm rupture leads to a subarachnoid hemorrhage with a very high mortality rate of 45-50%. Despite the high importance of this disease there are no criteria for assessing the probability of aneurysm rupture. Moreover, mechanisms of aneurysm development and rupture are not fully understood until now. METHODS: Biomechanical and numerical computer simulations allow us to estimate the behavior of vessels in normal state and under pathological conditions as well as to make a prediction of their postoperative state. Biomechanical studies may help clinicians to find and investigate mechanical factors which are responsible for the initiation, growth and rupture of the cerebral aneurysms. RESULTS: In this work, biomechanical and numerical modeling of healthy and pathological cerebral arteries was conducted. Patient-specific models of the basilar and posterior cerebral arteries and patient-specific boundary conditions at the inlet were used in numerical simulations. A comparative analysis of the three vascular wall models (rigid, perfectly elastic, hyperelastic) was performed. Blood flow and stress-strain state of the two posterior cerebral artery aneurysm models was compared. CONCLUSIONS: Numerical simulations revealed that hyperelastic material most adequately and realistically describes the behavior of the cerebral vascular walls. The size and shape of the aneurysm have a significant impact on the blood flow through the affected vessel and on the effective stress distribution in the aneurysm dome. It was shown that large aneurysm is more likely to rupture than small aneurysm. PMID- 27406683 TI - SUPPRESSING A PEROXIDASE GENE REDUCES SURVIVAL IN THE WHEAT APHID Sitobion avenae. AB - Peroxidases (POXs) make up a large superfamily of enzymes that act in a wide range of biological mechanisms, including maintaining appropriate redox balances within cells, among other actions. In this study, we cloned a sequence that encodes a POX protein, SaPOX, from wheat aphids, Sitobion avenae. Amino acid sequence alignment showed the SaPOX sequence was conserved with POXs from other insect species. SaPOX mRNA accumulations were present in all nymphal and adult stages, at higher levels during the first and second instar, and lower during later stages in the life cycle. Ingestion of dsRNA specific to POX led to reduced SaPOX mRNA accumulation. Sitobion avenae nymphs continuously exposed to dietary dsPOX via an artificial diet led to reduced survival rate and ecdysis index. We infer that POX is important to maintain the growth and development of S. avenae. PMID- 27406684 TI - Ribosomal binding and antibacterial activity of ethylene glycol-bridged apidaecin Api137 and oncocin Onc112 conjugates. AB - Recent surveillance data on antimicrobial resistance predict the beginning of the post-antibiotic era with pan-resistant bacteria even overcoming polymyxin as the last available treatment option. Thus, new substances using novel modes of antimicrobial action are urgently needed to reduce this health threat. Antimicrobial peptides are part of the innate immune system of most vertebrates and invertebrates and accepted as valid substances for antibiotic drug development efforts. Especially, short proline-rich antimicrobial peptides (PrAMP) of insect origin have been optimized for activity against Gram-negative strains. They inhibit protein expression in bacteria by blocking the 70S ribosome exit tunnel (oncocin-type) or the assembly of the 50S subunit (apidaecin-type binding). Thus, apidaecin analog Api137 and oncocin analog Onc112 supposedly bind to different nearby or possibly partially overlapping binding sites. Here, we synthesized Api137/Onc112-conjugates bridged by ethylene glycol spacers of different length to probe synergistic activities and binding modes. Indeed, the antimicrobial activities against Escherichia coli and Pseudomonas aeruginosa improved for some constructs, although the conjugates did not bind better to the 70S ribosome of E. coli than Api137 and Onc112 using 5(6)-carboxyfluorescein labelled Api137 and Onc112 in a competitive fluorescence polarization assay. In conclusion, Api137/Onc112-conjugates showed increased antimicrobial activities against P. aeruginosa and PrAMP-susceptible and -resistant E. coli most likely because of improved membrane interactions, whereas the interaction to the 70S ribosome was most likely not improved relying still on the independent apidaecin- and oncocin-type binding modes. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27406685 TI - A cross-shear deformation for optimizing the strength and ductility of AZ31 magnesium alloys. AB - Magnesium alloys have recently attracted great interest due their lightweight and high specific strength. However, because of their hexagonal close-packed structure, they have few active slip systems, resulting in poor ductility and high mechanical anisotropy at room temperature. In the present work, we used a cross-shear deformation imposed by a differential speed rolling (DSR) technique to improve the room temperature strength and ductility of AZ31 magnesium alloy sheets. To introduce the cross-shear deformation, the sheets were rotated 180 degrees around their longitudinal axis between the adjacent passes of DSR. The sheets of the AZ31 alloy subjected to the cross-shear deformation showed a uniform fine microstructure (1.2 +/- 0.1 MUm) with weak basal textures. The fabricated sheets showed a simultaneous high ultimate tensile strength and elongation-to-failure, i.e., ~333 MPa and ~21%, respectively. These were explained based on the structural features evolved due to the cross-shear deformation by DSR. The high strength was attributed to the uniform fine microstructure, whereas the high ductility was explained based on the basal texture weakening. PMID- 27406686 TI - Fe3O4@Carbon Nanosheets for All-Solid-State Supercapacitor Electrodes. AB - Fe3O4@carbon nanosheet composites were synthesized using ammonium ferric citrate as the Fe3O4/carbon precursor and graphene oxide as the structure-directing agent under a hydrothermal process. The surface chemical compositions, pore structures, and morphology of the composite were analyzed and characterized by nitrogen adsorption isotherms, TG analysis, FT-IR, X-ray photoelectron energy spectrum, transmission electron microscopy, and scanning electron microscopy. The composites showed excellent specific capacitance of 586 F/g, 340 F/g at 0.5 A/g and 10 A/g. The all-solid-state asymmetric supercapacitor device assembled using carbon nanosheets in situ embedded Fe3O4 composite and porous carbon showed a largest energy density of 18.3 Wh/kg at power density of 351 W/kg in KOH/PVA gel electrolyte. The synergism of high special surface to volume ratio, mesoporous structure, graphene-based conduction paths, and Fe3O4 nanoparticles provided a high surface area of ion-accessibility, high electric conductivity, and the utmost utilization of Fe3O4 and resulted in excellent specific capacitance, outstanding rate capability and cycling life as all-solid-state supercapacitor electrodes. PMID- 27406687 TI - Coping with interpersonal mistreatment: the role of emotion regulation strategies and supervisor support. AB - AIM: To examine whether the impact of mistreatment by patients on nurses' burnout can be exacerbated or attenuated depending on emotion-regulation strategies, and to explore the moderating role of supervisor support in the relationship between mistreatment and deep acting. BACKGROUND: Aggression from patients is known to contribute significantly to nurse burnout. To date, the moderating role of emotion regulation strategies in the mistreatment-outcomes relationship has seldom been considered. METHODS: The sample consisted of 105 nurses who were working while studying for their Master's degree. Data were collected using self reported questionnaires. The research hypotheses were tested using hierarchical regression analyses. RESULTS: Mistreatment and surface acting significantly contributed to nurse burnout. Deep acting had a buffering effect on the relationship between mistreatment and depersonalisation. The results also indicate that supervisor support was negatively associated with surface acting and may increase deep acting in response to mistreatment. CONCLUSION: The use of an effective strategy for regulating emotions and supervisor support can protect nurses from the depletion of emotional resources. IMPLICATIONS FOR NURSING MANAGEMENT: By introducing emotion-regulation skills training and by encouraging the availability of support from supervisors, health-care organisations can help nurses better cope with emotionally charged interactions. PMID- 27406688 TI - Diet and Dementia, is there a Link? A Systematic Review. AB - The aim of this systematic review was to determine whether there is cogent and compelling evidence in the published literature for a link between dementia and nutrition. Six case control studies and 5 longitudinal investigations were included. Most of these studies were methodologically flawed. No clear association emerged between nutritional factors and dementia. There were some weak, positive but unconfirmed associations between meat consumption, intake of total fat, saturated fat and cholesterol with dementia incidence. Conversely, regular wine and fish consumption was associated with a decrease of dementia incidence, a finding which was also unconfirmed by independent data. It is concluded that, at present, no firm links have been established between nutritional factors and dementia. The few associations that have been suggested are potentially important and should be investigated further. PMID- 27406689 TI - Maternal Responsiveness of Neonatally Undernourished and Sensory Stimulated Rats: Rehabilitation of Maternal Behavior. AB - The interaction between neonatal food deprivation and early sensory stimulation on four maternal behavioral components of Wistar strain rats was investigated. Dams neonatally underfed by daily mother-litter separation (Experiment 1), showed significant reductions in nest-rating and nursing time as well as increased retrieving latencies and selfgrooming responses compared to controls. Mothers which were neonatally undernourished by the nipple-ligation of their mothers (Experiment 2), exhibited less alterations in nest ratings, nursing time and retrieving latencies with no significant differences in the frequency of self grooming responses, in comparison to controls. Neonatal handling and the exposure to a sensory enriched environment in Experiment 1, ameliorated most of the alterations of neonatally underfed mothers. Moreover, in Experiment 2, the increase in the neonatal sensory stimulation only improves nest ratings performance without consistent effects upon other maternal behavioral responses. Data suggest that sensory stimulation at critical stages of brain ontogeny is able to compensate long-term maternal behavioral deficiencies associated to a severe neonatal undernutrition (Experiment 1), with variable effects following a mild food intake deprivation (Experiment 2). PMID- 27406690 TI - Volume of the Sexually Dimorphic Nucleus of the Preoptic Area in Rats Exposed to a Maternal High Fat Diet. AB - Mice and rats exposed to a maternal diet high in fat have an increased risk of reproductive system tumors later in life. To test whether a part of the hypothalamus associated with sex differentiation, the sexually dimorphic nucleus of the preoptic area (SDN-POA), might be involved, this nucleus was measured in the offspring of female rats on a high, or low fat diet during pregnancy and nursing. The measurements showed that the SDN-POA was smaller in female offspring exposed to a maternal high fat diet than in female offspring exposed to a maternal low fat diet. This could result in endocrine disturbances and thus provide a possible explanation for the linkage between high fat exposure prenatally and increased female reproductive system cancer. PMID- 27406691 TI - A Low Protein, High Carbohydrate Diet Attenuates Alcohol Intake in Rats. AB - To test whether a tryptophan-enhancing diet will reduce alcohol intake as serotonergic drugs do, two studies were conducted. In Experiment 1, 32 male, alcohol-drinking rats were randomly assigned to one of four isocaloric diets containing 25%-protein/65%-carbohydrate, 25%-protein/4%-carbohydrate, 4% protein/65%-carbohydrate, or 4%-protein/4%-carbohydrate. Following a baseline week during which they ate standard lab chow, rats were offered their assigned experimental diet, water, and 5%-alcohol solution ad lib for three weeks. Alcohol and diet intakes were measured daily. In Experiment 2, 32 naive male, alcohol drinking rats were assigned to one of the experimental diets used in Experiment 1. Following a one-week baseline, rats were offered their assigned diet, water, and 5%-alcohol/1%-sucrose solution ad lib for two weeks and then were switched back to standard lab chow for one week, with alcohol intake measured daily. Rats consuming the low protein, high carbohydrate diet drank 60-80% less alcohol than did rats offered other diets. This reduction in alcohol intake is most likely due to increased brain serotonin levels produced by the dietary manipulation. PMID- 27406692 TI - Impaired Response of Serum IGF-I Levels to Puberty in Previously Malnourished Adolescents. AB - Serum levels of IGF-I were measured in Barbadian children, aged 9-15 years, half of whom had experienced protein-energy malnutrition limited to the first year of life. Despite current nutritional adequacy, menarche was delayed more than one year in the girls with a history of early malnutrition and their IGF-I levels failed to show the 60% postmenarchic increase seen in the controls. In addition, the IGF-I levels of boys and girls with prior malnutrition in infancy were not significantly correlated with current anthropometric measurements, whereas IGF-I values of control boys and girls were significantly correlated for almost every growth parameter. Infantile malnutrition may cause an alteration in hypothalamic function resulting both in delayed onset of hypothalamic pituitary functions needed for puberty, and in an impaired growth hormone-IGF-I response. PMID- 27406693 TI - Acute Leptin Administration Increases Hypothalamic Expression of Prepro-orexin mRNA. AB - The hypothalamus plays a central role in the integrated control of feeding. Thus, leptin has been shown to inhibit food intake apparently by inhibition of hypothalamic NPY. It has been proposed that the recently discovered orexigenic peptides named orexins could play a role analogous to that of NPY in the control of feeding. To test this hypothesis we determined the relative levels of hypothalamic prepro-orexin mRNA expression 2 h after a single dose (1 mg/kg, ip) of recombinant murine leptin in 48 h fasted mice by semiquantitative RT-PCR. We found an unexpected increase (34%; p < 0.04) of prepro-orexin mRNA which indicates that the neuronal pathways controlling feeding behaviour are more complex than initially thought and that the short-term regulation of neurotransmitters which control food intake may be different than medium- or long term. PMID- 27406694 TI - The Analysis of Variance (ANOVA). AB - This is the fourth in a series of articles devoted to a simplified description of experimental design, statistical analysis and interpretation. This article deals with a basic description of the analysis of variance (ANOVA) and its methods of computation and hypothesis testing. Examples are provided in which a one-way ANOVA is analyzed; methods for post-ANOVA pair-wise comparisons of treatment means are also discussed. PMID- 27406695 TI - A comparison of hemagglutination inhibition and neutralization assays for characterizing immunity to seasonal influenza A. AB - BACKGROUND: Serum antibody to influenza can be used to identify past exposure and measure current immune status. The two most common methods for measuring this are the hemagglutination inhibition assay (HI) and the viral neutralization assay (NT), which have not been systematically compared for a large number of influenza viruses. METHODS: A total of 151 study participants from near Guangzhou, China, were enrolled in 2009 and provided serum. HI and NT assays were performed for 12 historic and recently circulating strains of seasonal influenza A. We compared titers using Spearman correlation and fit models to predict NT using HI results. RESULTS: We observed high positive mean correlation between HI and NT assays (Spearman's rank correlation, rho=.86) across all strains. Correlation was highest within subtypes and within close proximity in time. Overall, an HI=20 corresponded to NT=10, and HI=40 corresponded to NT=20. Linear regression of log(NT) on log(HI) was statistically significant, with age modifying this relationship. Strain-specific area under a curve (AUC) indicated good accuracy (>80%) for predicting NT with HI. CONCLUSIONS: While we found high overall correspondence of titers between NT and HI assays for seasonal influenza A, no exact equivalence between assays could be determined. This was further complicated by correspondence between titers changing with age. These findings support generalized comparison of results between assays and give further support for use of the hemagglutination inhibition assay over the more resource intensive viral neutralization assay for seasonal influenza A, although attention should be given to the effect of age on these assays. PMID- 27406697 TI - Nanomanipulation and controlled self-assembly of metal nanoparticles and nanocrystals for plasmonics. AB - Localized surface plasmon resonances (LSPRs) associated with metallic nanostructures offer unique possibilities for light concentration beyond the diffraction limit, which can lead to strong field confinement and enhancement in deep subwavelength regions. In recent years, many transformative plasmonic applications have emerged, taking advantage of the spectral and spatial tunability of LSPRs enabled by near-field coupling between constituent metallic nanostructures in a variety of plasmonic metastructures (dimers, metamolecules, metasurfaces, metamaterials, etc.). For example, the "hot spot" formed at the interstitial site (gap) between two coupled metallic nanostructures in a plasmonic dimer can be spectrally tuned via the gap size. Capitalizing on these capabilities, there have been significant advances in plasmon enhanced or enabled applications in light-based science and technology, including ultrahigh sensitivity spectroscopies, light energy harvesting, photocatalysis, biomedical imaging and theranostics, optical sensing, nonlinear optics, ultrahigh-density data storage, as well as plasmonic metamaterials and metasurfaces exhibiting unusual linear and nonlinear optical properties. In this review, we present two complementary approaches for fabricating plasmonic metastructures. We discuss how meta-atoms can be assembled into unique plasmonic metastructures using a variety of nanomanipulation methods based on single- or multiple-probes in an atomic force microscope (AFM) or a scanning electron microscope (SEM), optical tweezers, and focused electron-beam nanomanipulation. We also provide a few examples of nanoparticle metamolecules with designed properties realized in such well controlled plasmonic metastructures. For the spatial controllability on the mesoscopic and macroscopic scales, we show that controlled self-assembly is the method of choice to realize scalable two-dimensional, and three-dimensional plasmonic metastructures. In the section of applications, we discuss some key examples of plasmonic applications based on individual hot spots or ensembles of hot spots with high uniformity and improved controllability. PMID- 27406696 TI - Can Playing an End-of-Life Conversation Game Motivate People to Engage in Advance Care Planning? AB - BACKGROUND: Advance care planning (ACP) involves several behaviors that individuals undertake to prepare for future medical care should they lose decision-making capacity. The goal of this study was to assess whether playing a conversation game could motivate participants to engage in ACP. METHODS: Sixty eight English-speaking, adult volunteers (n = 17 games) from communities around Hershey, Pennsylvania, and Lexington, Kentucky, played a conversation card game about end-of-life issues. Readiness to engage in 4 ACP behaviors was measured by a validated questionnaire (based on the transtheoretical model) immediately before and 3 months postgame and a semistructured phone interview. These behaviors were (1) completing a living will; (2) completing a health-care proxy; (3) discussing end-of-life wishes with loved ones; and (4) discussing quality versus quantity of life with loved ones. RESULTS: Participants' (n = 68) mean age was 51.3 years (standard deviation = 0.7, range: 22-88); 94% of the participants were caucasian and 67% were female. Seventy-eight percent of the participants engaged in ACP behaviors within 3 months of playing the game (eg, updating documents, discussing end-of-life issues). Furthermore, 73% of the participants progressed in stage of change (ie, readiness) to perform at least 1 of the 4 behaviors. Scores on measures of decisional balance and processes of change increased significantly by 3 months postintervention. CONCLUSION: This pilot study found that individuals who played a conversation game had high rates of performing ACP behaviors within 3 months. These findings suggest that using a game format may be a useful way to motivate people to perform important ACP behaviors. PMID- 27406698 TI - WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease. AB - We have performed whole-exome sequencing in a family trio with a 16-year-old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans-phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother. PMID- 27406700 TI - [Formula: see text]Naturalistic tasks performed in realistic environments: a review with implications for neuropsychological assessment. AB - OBJECTIVE: Understanding functional abilities for those with neurologic disorders is a growing area of investigation. In this paper, performance-based naturalistic tasks used to assess cognitive and functional deficits were reviewed to determine current evidence for effectiveness as valid and reliable assessment measures and to make recommendations for future research. METHOD: Performance-based naturalistic tasks were defined as observable, rule-based, open-ended tasks completed in an environment that either mimics the real world or is the real world. Thirty-eight studies, discussed by the environment in which the task was performed (i.e. vocational, kitchen, hospital/store, and home), were reviewed. RESULTS: Many studies were found to have significant methodological limitations (e.g. low sample size) and few studies evaluated the relationship between performance on the naturalistic task and everyday functioning. The efficacy of using naturalistic tasks to better understand functional status has yet to be clearly demonstrated across neurologic populations. Numerous factors, including ease of use, limited research on how to best utilize these tasks, and cost impact the use of naturalistic tasks. Nonetheless, given the promising theoretical foundation, opportunities are ripe for further development of assessment strategies that use contextually relevant environments and allow for enhanced safety and controllability of tasks, increased face validity, capitalization on automatic processes, and improved ecological validity. CONCLUSIONS: Future research is needed to increase the knowledge base regarding the use of naturalistic tasks, especially as they relate to everyday functioning, because of the potential benefits to advance the standard of care for individuals with neurologic conditions. PMID- 27406699 TI - Dual band metamaterial perfect absorber based on artificial dielectric "molecules". AB - Dual band metamaterial perfect absorbers with two absorption bands are highly desirable because of their potential application areas such as detectors, transceiver system, and spectroscopic imagers. However, most of these dual band metamaterial absorbers proposed were based on resonances of metal patterns. Here, we numerically and experimentally demonstrate a dual band metamaterial perfect absorber composed of artificial dielectric "molecules" with high symmetry. The artificial dielectric "molecule" consists of four "atoms" of two different sizes corresponding to two absorption bands with near unity absorptivity. Numerical and experimental absorptivity verify that the dual-band metamaterial absorber is polarization insensitive and can operate in wide-angle incidence. PMID- 27406701 TI - Editorial for "Computational Electrocardiography: Revisiting Holter ECG Monitoring". PMID- 27406702 TI - Oligodendroglial deletion of ESCRT-I component TSG101 causes spongiform encephalopathy. AB - BACKGROUND INFORMATION: Vacuolation of the central nervous system (CNS) is observed in patients with transmissible spongiform encephalopathy, HIV-related encephalopathy and some inherited diseases, but the underlying cellular mechanisms remain poorly understood. Mice lacking the mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase develop progressive, widespread spongiform degeneration of the CNS. MGRN1 ubiquitinates and regulates tumour susceptibility gene 101 (TSG101), a central component of the endosomal trafficking machinery. As loss of MGRN1 is predicted to cause partial TSG101 loss-of-function, we hypothesised that CNS vacuolation in Mgrn1 null mice may be caused by the accumulation of multi-cisternal endosome-like 'class E' vacuolar protein sorting (vps) compartments similar to those observed in Tsg101-depleted cells in culture. RESULTS: To test this hypothesis, Tsg101 was deleted from mature oligodendroglia in vivo. This resulted in severe spongiform encephalopathy, histopathologically similar to that observed in Mgrn1 null mutant mice but with a more rapid onset. Vacuoles in the brains of Tsg101-deleted and Mgrn1 mutant mice labelled with endosomal markers, consistent with an endosomal origin. Vacuoles in the brains of mice inoculated with Rocky Mountain Laboratory (RML) prions did not label with these markers, indicating a different origin, consistent with previously published studies that indicate RML prions have a primary effect on neurons and cause vacuolation in an MGRN1-independent manner. Oligodendroglial deletion of Rab7, which mediates late endosome-to-lysosome trafficking and autophagosome lysosome fusion, did not cause spongiform change. CONCLUSIONS: Our data suggest that the formation of multi-cisternal 'class E' vps endosomal structures in oligodendroglia leads to vacuolation. SIGNIFICANCE: This work provides the first evidence that disrupting multi-vesicular body formation in oligodendroglia can cause white matter vacuolation and demyelination. HIV is known to hijack the endosomal sorting machinery, suggesting that HIV infection of the CNS may also act through this pathway to cause encephalopathy. PMID- 27406703 TI - [Not Available]. PMID- 27406704 TI - Surgery in MEN 2A Patients Older Than 5 Years with Micro-MTC: Outcome at Long term Follow-up. AB - In multiple endocrine neoplasia syndrome type 2A (MEN 2A), early total thyroidectomy (TT; performed before the age of 5 years) is the best option to prevent medullary thyroid carcinoma (MTC) development, but the management of MEN 2A patients diagnosed after childhood is still under debate. Seventeen consecutive patients diagnosed with MEN 2A after the age of 5 years (mean age, 23.3 years) with a pathologic diagnosis of micro-MTC without nodal involvement were enrolled. All patients underwent TT with thymectomy and central compartment lymph node dissection. During surgery, parathyroid tissue removal occurred in 14 patients. No major postoperative complications nor persistent hypoparathyroidism was observed. After a mean follow-up of 16.6 years, no patient developed primary hyperparathyroidism or disease recurrence. Even if TT is recommended before the age of 5, when MEN 2A diagnosis is performed after this age in micro-MTC without nodal involvement, TT with thymectomy and central compartment lymphadenectomy can provide good oncologic and functional results. PMID- 27406705 TI - Effects of Covering Surgical Wounds with Polyglycolic Acid Sheets for Posttonsillectomy Pain. AB - Postoperative pain is a remaining issue in tonsillectomy. Polyglycolic acid (PGA) is a biocompatible material used for absorbent suture reinforcement, and its sheet has been applied for covering defects after resection of oral carcinoma. The aim of this study is to examine whether the attachment of a PGA sheet to surgical wounds would reduce posttonsillectomy pain. In this prospective single blind study, 17 consecutive adult patients were recruited who needed to undergo tonsillectomy, mainly due to habitual tonsillitis. Following bilateral tonsillectomies, a PGA sheet was attached with fibrin glue to only 1 side, without notification to patients of which side. Postoperative pain of each side was separately evaluated with a visual analog scale at 4 time points: before each meal and before sleep. Postoperative pain of both the PGA sheet-attached and nonattached sides was most severe before breakfast among 4 time points. Postoperative pain measured before breakfast was significantly more severe in the PGA sheet-attached side than the nonattached side. As such, this study provided solid data on the negative effects of PGA sheeting on posttonsillectomy pain. PMID- 27406706 TI - Endoscopic Endonasal Repair of Septal Perforation with Interpositional Auricular Cartilage Grafting via a Mucosal Regeneration Technique. AB - We evaluated the efficacy of interpositional auricular cartilage grafting for perforation with an endoscopic endonasal approach via a mucosal regeneration technique. In total, 12 patients with symptomatic septal perforations were operated on by way of an endoscopic endonasal approach after an adequately sized cartilage graft was harvested. The graft was inserted between the circumferentially incised and elevated flaps of the perforation and secured by vertical and horizontal nonabsorbable aligning approximation stitches and prolonged placement of silicone splints. The average perforation size was 12.3 mm (range, 4-19 mm). Bleeding, incrustation, pain, whistling respiration, and nasal congestion symptoms were relieved entirely in 10 of 12 patients (83.3%) who had successful treatment. This study showed that an endoscopic endonasal approach via a mucosal regeneration technique without direct mucosa-to-mucosa repair can be applied successfully without disrupting the neighboring nasal structures for septal perforations up to 20 mm and as effectively as other, more complex surgical interventions. PMID- 27406707 TI - Cricohyoidoepiglottopexy in Laryngeal Trauma. PMID- 27406708 TI - The pathology of incipient polymicrogyria. AB - OBJECTIVE: To characterise the early tissue changes of post encephaloclastic polymicrogyria in the human fetus. METHODS: We identified and reviewed the clinical histories and autopsy pathology of post ischemic fetal cerebral cortical injury at less than 30weeks gestational age (GA). The histology of local cortical abnormalities was examined with neuronal, glial, microglial and vascular immunohistochemical markers. RESULTS: We identified eight cases ranging from 18 to 29weeks GA: 5 cases show full thickness cortical infarcts and 3 show periSylvian post-ischemic necrosis of the cerebral cortex. The maximal age is less than 10weeks after injury. There are abnormalities in gross fissuration as early as one month after injury. Disruption of the pia limitans was associated with a microglial and glial response and full thickness cortical injury. Macrophages were often seen accumulating deep to abnormal cortex. Hyperplasia of the subpial granular cell layer was universal in perilesional cortex. Cajal Retzius neuron hyperplasia, aggregation, and both superficial and deep displacement were noted. Where there was loss and dispersal of early cortical pyramidal neurons there was usually no pseudolaminar necrosis. Radial glia by 18weeks GA showed altered growth patterns and lateral branching. Altered migration of primitive elements was often prominent. Particularly prior to 20weeks GA subadjacent subplate neurons showed striking hypertrophy. CONCLUSIONS: The array of histological changes encompasses all tissue elements of the affected brains, early in the evolution polymicrogyria. Although subpial alterations were ubiquitous, not all changes are referable to alterations in the pia limitans. The role of the necroinflammatory response in the genesis of abnormal cytoarchitecture deserves further study. PMID- 27406710 TI - Gordonia hongkongensis sp. nov., isolated from blood culture and peritoneal dialysis effluent of patients in Hong Kong. AB - Two bacterial strains, HKU50T and HKU46, were isolated in Hong Kong from the blood culture and the peritoneal dialysis effluent of two patients. The strains are Gram-stain-positive, acid-fast, non-motile, non-sporulating bacilli. They grow on Columbia agar with 5 % defibrinated sheep blood and brain-heart infusion agar under aerobic conditions with 5 % CO2 at 37 degrees C as pink-to-orange, non-haemolytic colonies. The strains are catalase-positive and oxidase-negative, and have a unique biochemical profile distinguishable from other closely related species. DNA sequencing revealed that both isolates possessed multiple intra genomic 16S rRNA gene copies (99.8-100 % sequence identities to Gordonia lacunae NRRL B-24551T and Gordonia terrae NRRL B-16283T). Phylogenetic analysis of the 16S rRNA gene, secA1 and gyrB showed that the two isolates formed a distinct branch within the genus Gordonia and were most closely related to G. lacunae and G. terrae. DNA-DNA hybridization demonstrated <=53.7 % and <=49.4 % DNA relatedness between the two isolates and G. lacunae, and between the two isolates and G. terrae, respectively. Hierarchical cluster analysis of MALDI-TOF MS main spectrum profiles showed that strains HKU50T and HKU46 were closely related to each other, but were distinct from G. lacunae, G. terrae, or any other species of the genus Gordonia in the Bruker database. The chemotaxonomic traits of the two strains were highly similar, and the major fatty acids were summed feature 4 (iso C15 : 0 2-OH/C16 : 1trans-9), C16 : 0, C18 : 1cis-9, and tuberculostearic acid. A novel species named Gordonia hongkongensis sp. nov. is proposed to accommodate strains HKU50T and HKU46, with strain HKU50T (=CCOS 955T=CIP 111027T=NBRC 111234T=NCCP 16210T) as the type strain. PMID- 27406709 TI - Valosin-containing protein (VCP)-Adaptor Interactions are Exceptionally Dynamic and Subject to Differential Modulation by a VCP Inhibitor. AB - Protein quality control (PQC) plays an important role in stemming neurodegenerative diseases and is essential for the growth of some cancers. Valosin-containing protein (VCP)/p97 plays a pivotal role in multiple PQC pathways by interacting with numerous adaptors that link VCP to specific PQC pathways and substrates and influence the post-translational modification state of substrates. However, our poor understanding of the specificity and architecture of the adaptors, and the dynamic properties of their interactions with VCP hinders our understanding of fundamental features of PQC and how modulation of VCP activity can best be exploited therapeutically. In this study we use multiple mass spectrometry-based proteomic approaches combined with biophysical studies to characterize the interaction of adaptors with VCP. Our results reveal that most VCP-adaptor interactions are characterized by rapid dynamics that in some cases are modulated by the VCP inhibitor NMS873. These findings have significant implications for both the regulation of VCP function and the impact of VCP inhibition on different VCP-adaptor complexes. PMID- 27406711 TI - Modifying effect of intravenous laser therapy on the protein expression of arginase and epidermal growth factor receptor in type 2 diabetic patients. AB - The epidermal growth factor receptor (EGFR) signaling pathway may be involved in cell activation and may influence the neuronal microenvironment, microglia activation, and production of proinflammatory cytokines. Arginase and nitric oxide synthase (NOS) both use L-arginine as a common substrate. Decreasing the arginase expression may increase L-arginine consumption by NOS and increase nitric oxide (NO) synthesis. Intravenous laser blood irradiation (ILBI) is an effective systemic treatment for different pathologies including diabetes mellitus. Previous studies have shown that low-level laser therapy can have an effect on the release of certain cytokines and growth factors. The aim of this study was to evaluate the effects of ILBI on the expression of arginase and epidermal growth factor receptor in type 2 diabetic patients. We used 630 nm red laser light, 1.5 mW, continuous mode, intravenously for 30 min in 13 type 2 diabetic patients and compared their blood samples using the flow cytometry technique, before and after ILBI. The difference between the percentage of cells before and after therapy was analyzed using repeated-measures ANOVA, and the relationship between EGFR and arginase expression in blood and tissue was evaluated by calculating the Pearson correlation coefficient. We found a significant decrease in the expression of both arginase- and EGFR-positive cells after laser therapy (P < 0.01). In conclusion, laser therapy may have a beneficial effect for diabetic patients via decreasing arginase expression and activation of the NOS/NO pathway which increases NO production and vasodilation, and decreasing EGFR expression which may reduce neuroinflammation and its secondary damages. PMID- 27406713 TI - Messages from forgotten friends: classic cell adhesion molecules inhibit regeneration too. PMID- 27406714 TI - Staff shortages are impeding efforts to improve cancer outcomes in England. PMID- 27406712 TI - Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics. AB - The reactive dicarbonyl metabolite methylglyoxal (MG) is the precursor of the major quantitative advanced glycation endproducts (AGEs) in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. The glyoxalase system in the cytoplasm of cells provides the primary defence against dicarbonyl glycation by catalysing the metabolism of MG and related reactive dicarbonyls. Dicarbonyl stress is the abnormal accumulation of dicarbonyl metabolites leading to increased protein and DNA modification contributing to cell and tissue dysfunction in ageing and disease. It is produced endogenously by increased formation and/or decreased metabolism of dicarbonyl metabolites. Dicarbonyl stress contributes to ageing, disease and activity of cytotoxic chemotherapeutic agents. It contributes to ageing through age-related decline in glyoxalase 1 (Glo-1) activity. Glo-1 has a dual role in cancer as a tumour suppressor protein prior to tumour development and mediator of multi-drug resistance in cancer treatment, implicating dicarbonyl glycation of DNA in carcinogenesis and dicarbonyl-driven cytotoxicity in mechanism of action of anticancer drugs. Glo-1 is a driver of cardiovascular disease, likely through dicarbonyl stress-driven dyslipidemia and vascular cell dysfunction. Dicarbonyl stress is also a contributing mediator of obesity and vascular complications of diabetes. There are also emerging roles in neurological disorders. Glo-1 responds to dicarbonyl stress to enhance cytoprotection at the transcriptional level through stress-responsive increase of Glo-1 expression. Small molecule Glo-1 inducers are in clinical development for improved metabolic, vascular and renal health and Glo-1 inhibitors in preclinical development for multidrug resistant cancer chemotherapy. PMID- 27406716 TI - Adherence in children with growth hormone deficiency treated with r-hGH and the easypodTM device. AB - PURPOSE: Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypodTM, an electronic, fully automated injection device designed to track the time, date and dose administered. METHODS: Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypodTM, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. RESULTS: The easypodTM data showed that 56.7 % of the patients were considered to be fully (>=92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. CONCLUSIONS: The injection-recording system and other characteristics of easypodTM could enhance the ability of physicians to monitor adherence to r-hGH treatment. PMID- 27406717 TI - Production of a new tetracyclic triterpene sulfate metabolite sambacide by solid state cultivated Fusarium sambucinum B10.2 using potato as substrate. AB - The aim of this work is to explore integracide analogues from secondary metabolites of microorganisms. A new tetracyclic triterpene sulfate was produced by solid-state fermentation (SSF) with Fusarium sambucinum B10.2. The tetracyclic triterpene sulfate was identified as (3S,5R,10S,11S,12S,13R,17R,20R)-4,4 dimethylergosta-8,14,24-triene-3,11,12-triol-12-acetate, 3-sulfate on the basis of HRESIMS, NMR and electronic circular dichroism (ECD) spectra and named sambacide (1). The antibacterial and antifungal assays of sambacide (1) showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli. The fermentation conditions including culture media, fermentation temperature and time, were optimized. And potato was selected as the fermentation substrate, 28 degrees C was used as the fermentation temperature, and 20-days fermentation time was determined for F. sambucinum-SSF to produce sambacide (1) with a high yield of 19.04+/-0.82g/kg. This paper provides an efficient approach to produce the antibacterial and antifungal agent sambacide (1) in a very high yield. PMID- 27406719 TI - Cardiovascular disease risk assessment in HIV: navigating data-sparse zones. PMID- 27406718 TI - Heartbeat: Prediction of coronary disease risk with cardiac troponin in the general population. PMID- 27406720 TI - Interview: Professor Peter Weissberg, Medical Director of the BHF. PMID- 27406721 TI - Chronic Lymphocytic Leukemia: An Update on Current Treatment Approaches. AB - During the last two decades, important progress has been made in the understanding of the biology, natural history, and prognosis of chronic lymphocytic leukemia (CLL). In addition, new and more effective treatment modalities are changing the objectives of treatment in patients with CLL. In this regard, the purine analogues offer great promise and fludarabine is already considered the treatment of choice for patients failing standard therapies. The role of purine analogues either alone or combined with other agents as front-line therapy is being actively investigated. Certain situations (e.g, autoimmune cytopenias, hypersplenism) require special treatment approaches (e.g., corticosteroids, splenectomy). Transplants of hemopoietic progenitor cells are also increasingly performed. As a result of these advances, treatment of subjects with CLL can be decided on the basis of the individual risk of each patient and the possibility of curing some of them may become a realistic objective. PMID- 27406722 TI - Effect of GM-CSF, 1, 25-Dihydroxycholecalciferol (Vit.D) and All-Trans-Retinoic Acid (ATRA) on the Proliferation and Differentiation of MDS-Bone Marrow (BM) Cells In Vitro. AB - Myelodysplastic syndromes (MDS) are a heterogenous group of stem cell disorders characterized by an impaired differentiation of the pluripotent stem cell resulting in dysplastic changes of all three hemopoietic lineages. We studied the effect of vitamin D (Vit.D) or all-trans retinoic acid (ATRA; 10(-6) and 10(-8)M) in combination with GM-CSF on the proliferation and differentiation of mononuclear bone marrow-cells (MNC) of 48 MDS-patients as compared to 9 normal bone marrow (BM)-controls in a special colony assay: 30,000 MNC were cultured in agar plugs for 7 days (d) and the resulting colonies immunophenotyped in situ by a panel of monoclonal antibodies. In 14 of 48 cultured MDS-BM-samples hemopoietic clones could be grown which expressed myelomonocytic antigens (CD14 (21%*), CD15 (35%*)) as well as blast antigens (CD20 (9%*), CD34 (10%*), Glycophorin A (Glyco A, 18%*)) whereas all normal BM-colonies were negative for blast markers. Vit.D or ATRA in combination with GM-CSF could not induce an (immunologically measurable) increased differentiation (5 higher percentage of differentiated clones) as compared to GM-CSF alone. We conclude that Vit.D and ATRA have no sufficient differentiation effect on MDS-cells. Our colony assay in combination with immunophenotyping enables an in vitro measurement of differentiation and proliferation in MDS. We suggest the use of this technique to measure effects of therapy in the course of the disease. PMID- 27406723 TI - Effect of Interleukin-1 alpha and Interleukin-1 beta on Erythroid Progenitor Cell Growth in Serum Free Cultures: An In Vitro Study Relevant to the Pathogenesis of the Anemia of Chronic Disease. AB - It has been postulated that interleukin-lalpha (IL-lalpha) and interleukin-1beta (IL-1beta) play a role in the pathogenesis of the anemia of chronic disease by inhibiting the proliferation of human erythroid progenitor cells. In the course of investigating this hypothesis we found that IL-1 type I receptor (IL-1R) mRNA is expressed on erythroid progenitor enriched, primitive human hematopoietic cells (CD34+, c-kit-R(bright)) and on cells isolated from human erythroid burst forming colonies (BFU-E). Nevertheless, when CD34+, c-kit-R(bright) cells were exposed to IL-1alpha and IL-1beta in vitro, cloning efficacy of BFU-E and CFU-E in a serum free culture system was not inhibited. Moreover, in apparent contradiction to the hypothesis being tested, we found that both IL-1 isoforms actually increased the survival of human BFU-E in serum free, growth factor free medium. Accordingly, these results suggest that if IL-1 plays a role in the pathogenesis of the anemia of chronic disease, it is not due to a direct suppressive effect on erythroid cell growth. Rather, our data support the hypothesis that IL-1 may cause the elaboration of another inhibitory cytokine (s) by cells of the marrow microenvironment. PMID- 27406724 TI - Induction of Erythropoiesis by MHC-Mediated Cognate Interactions between B- and T Cells. AB - We have previously shown that the expression of membrane burst-promoting activity (mBPA), an erythropoietic cytokine, by B-lymphocytes is augmented by the addition of allogeneic effector cells to the B-cells. Here, we have examined immune mechanisms involved in the induction/promotion of erythropoiesis as assessed by the capacity of autologous and allogeneic peripheral blood lymphocytes to augment burst-forming unit-erythroid (BFU-E) in normal human bone marrow cells in vitro. Preincubation of mBPA-expressing human B-cells with monoclonal antibodies to major histocompatibility complex (MHC) antigens, abrogated erythropoietic activity of both autologous and allogeneic lymphocytes, suggesting that MHC antigens play a role in regulating the expression of the erythroid growth factor. Inhibition of BFU-E proliferation was also evident when antibodies to MHC class-I or class-II antigens were added directly to marrow culture. Furthermore, addition of anti-CD4 antibody to the cultures of PBL and autologous target BM cells markedly reduced erythroid proliferation induced by PBL. By contrast, anti-CD8 and control (UPC-10) monoclonal antibodies had no effect. These results provide evidence that MHC-mediated cognate interactions between T- and B-lymphocytes may participate in the control of erythropoiesis, either directly or by modulating mBPA function. PMID- 27406725 TI - Modulation of Platelet Aggregation Response by Factors Released from Polymorphonuclear Leukocytes. AB - Various studies, mostly done in vitro have suggested that there is interaction between platelets and polymorphonuclear leukocytes (PMNLs). Both the cells depending upon the experimental conditions release various mediators which modulate their reactivity. In the present review the effects of mediators released from PMNLs and their effect on platelet aggregation has been discussed. The present review summarizes various studies on the release of mediators such as free radicals, arachidonic acid and its metabolites, platelet activating factor, proteases, nitric oxide, ectonucleotidases and other uncharacterized factors from PMNLs. The effect of these mediators on the platelet aggregation response has also been discussed. PMID- 27406726 TI - The Management of Polycythaemia Vera. AB - Thrombo-embolic complications are the commonest cause of morbidity and mortality in untreated PV. Control of the PCV (<0.45) and platelet count (<400 x 10(9)/I) minimizes the risk of these complications. In addition, suppression of megakaryocytic proliferation delays myelofibrotic transformation, which is probably the 'natural' long-term outcome of PV. A small percentage of patients transform to acute leukaemia, particularly after myelofibrotic transformation. Leukaemic transformation is enhanced with some forms of myelosuppression, notably high accumulated doses of chlorambucil and (32)P. Venesection should be used initially to reduce the PCV and subsequently as required. The choice of myelosuppressive agent depend on the patients age. Older patients can be managed with (32)P, low-dose busulphan or pipobroman. Hydroxyurea has a role in the management of patients at all ages, although it possibly enhances the leukaemogenic risk. Therefore, agents such as interferon-alpha or anagrelide should be considered in younger patients. PMID- 27406727 TI - Leucocyte Immunophenotyping: The Need for Standardization. PMID- 27406728 TI - Post Chernobyl Hemoblastoses in the Republic of Belarus (brief communication). AB - Data on the incidence of acute leukemia (AL) in children in the Byelorus Republic is analysed and comparisons made between the incidence of AL prior and subsequent to the Chernobyl accident in 1986. The Byelorus Republic was directly and heavily contaminated at that time and careful records of the incidence of cases of AL and other malignancies have since been kept. Byelorus is divided into large administrative regions-oblasts-which are subdivided into raions. Both the levels of radiation and estimates of chemical pollution in these areas are available. Childhood AL incidence appears to be unrelated to radiation dosage in that no increases were seen in the more radiation contaminated areas. However there appeared to be a more likely relationship with chemical pollution. Adult AL and other myeloproliferative and lymphoproliferative disorders have appeared to increase since 1986 but again the authors attribute this more to rising levels of chemical pollution possibly associated with radiation as a coleukemogen. PMID- 27406729 TI - Myeloma Presenting in the Base of the Skull. AB - Of 385 consecutive patients with a proven diagnosis of myeloma seen over a 15 year period, only four presented with symptoms and signs due to involvement of the skull base. This rare occurrence is in striking contrast to the frequency with which radiologic changes can be demonstrated in the bones of the calvarium during the course of most individual's disease. Response to treatment was obtained in all four, of whom one is a longterm survivor. This experience is reported emphasising the need to consider the possibility of myeloma in people with unexplained craniospinal symptoms and signs. In addition, the radiologic changes are tabulated in the hope that a pattern may emerge which will alert physicians to the presence of this rare situation. PMID- 27406730 TI - Acute Lymphoblastic Leukemia Occurring in a Case of Chronic Lymphocytic Leukemia. AB - Chronic lymphocytic leukemia (CLL) is a disease characterized by variable clinical presentation and a prolonged course. However, a small proportion of cases may evolve to more aggressive forms. These include acute leukemic blastic crises of both myeloid and lymphoid types, prolymphocytoid transformation, lymphoma and multiple myeloma. We describe a case of B-CLL treated with chlorambucil, in whom a picture of acute lymphoblastic leukemia of pre-B type developed. The diagnosis of both forms of leukemia is well documented on the basis of morphological, cytochemical and immunological findings. Documentation and investigation of cases of ALL occurring in CLL is of importance to determine whether the transformation represents a clonal evolution of the original CLL or an independent second malignancy in an immunocomprimised patient. PMID- 27406731 TI - Construction of a recombinant Lactococcus lactis strain expressing a fusion protein of Omp22 and HpaA from Helicobacter pylori for oral vaccine development. AB - OBJECTIVES: To develop orally administrated anti-Helicobacter pylori vaccination, a Lactococcus lactis strain was genetically constructed for fusion expression of H. pylori protective antigens HpaA and Omp22. RESULTS: The fusion gene of omp22 and hpaA with an adapter encoding three glycines was cloned from a plasmid pMAL c2x-omp22-hpaA into Escherichia coli MC1061 and L. lactis NZ3900 successively using a shutter vector pNZ8110. Expression of the fusion gene in L. lactis was induced with nisin resulting in production of proteins with molecular weights of 50 and 28 kDa. Both of them were immunoreactive with mouse anti-H. pylori sera as determined via western blotting. Oral vaccination of BALB/c mice using the L. lactis strain carrying pNZ8110-omp22-hpaA elicited significant systematic humoral immune response (P < 0.05). CONCLUSIONS: This is the first report showing that a fusion protein of two H. pylori antigens was efficiently expressed in L. lactis with immunogenicity. This is a considerable step towards H. pylori vaccines. PMID- 27406734 TI - [Not Available]. PMID- 27406732 TI - Rhizobacterial Community Structures Associated with Native Plants Grown in Chilean Extreme Environments. AB - Chile is topographically and climatically diverse, with a wide array of diverse undisturbed ecosystems that include native plants that are highly adapted to local conditions. However, our understanding of the diversity, activity, and role of rhizobacteria associated with natural vegetation in undisturbed Chilean extreme ecosystems is very poor. In the present study, the combination of denaturing gradient gel electrophoresis and 454-pyrosequencing approaches was used to describe the rhizobacterial community structures of native plants grown in three representative Chilean extreme environments: Atacama Desert (ATA), Andes Mountains (AND), and Antarctic (ANT). Both molecular approaches revealed the presence of Proteobacteria, Bacteroidetes, and Actinobacteria as the dominant phyla in the rhizospheres of native plants. Lower numbers of operational taxonomic units (OTUs) were observed in rhizosphere soils from ATA compared with AND and ANT. Both approaches also showed differences in rhizobacterial community structures between extreme environments and between plant species. The differences among plant species grown in the same environment were attributed to the higher relative abundance of classes Gammaproteobacteria and Alphaproteobacteria. However, further studies are needed to determine which environmental factors regulate the structures of rhizobacterial communities, and how (or if) specific bacterial groups may contribute to the growth and survival of native plants in each Chilean extreme environments. PMID- 27406733 TI - Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. AB - Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases. PMID- 27406735 TI - Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case control assessment of the vaccine adverse event reporting system (VAERS) database. AB - Gardasil is a quadrivalent human papillomavirus (HPV4) vaccine that was approved for use by the US Food and Drug Administration in June 2006. HPV4 vaccine is routinely recommended for administration to women in the USA who are 11-12 years old by the Advisory Committee on Immunization Practices. Previous studies suggest HPV4 vaccine administration was associated with autoimmune diseases. As a consequence, an epidemiological assessment of the vaccine adverse event reporting system database was undertaken for adverse event reports associated with vaccines administered from 2006 to 2014 to 6-39 year-old recipients with a listed US residence and a specified female gender. Cases with the serious autoimmune adverse event (SAAE) outcomes of gastroenteritis (odds ratio (OR) 4.627, 95 % confidence interval (CI) 1.892-12.389), rheumatoid arthritis (OR 5.629, 95 % CI 2.809-12.039), thrombocytopenia (OR 2.178, 95 % CI 1.222-3.885), systemic lupus erythematosus (OR 7.626, 95 % CI 3.385-19.366), vasculitis (OR 3.420, 95 % CI 1.211-10.408), alopecia (OR 8.894, 95 % CI 6.255-12.914), CNS demyelinating conditions (OR 1.585, 95 % CI 1.129-2.213), ovarian damage (OR 14.961, 95 % CI 6.728-39.199), or irritable bowel syndrome (OR 10.021, 95 % CI 3.725-33.749) were significantly more likely than controls to have received HPV4 vaccine (median onset of initial symptoms ranged from 3 to 37 days post-HPV4 vaccination). Cases with the outcome of Guillain-Barre syndrome (OR 0.839, 95 % CI 0.601-1.145) were no more likely than controls to have received HPV4 vaccine. In addition, cases with the known HPV4-related outcome of syncope were significantly more likely than controls to have received HPV4 vaccine (OR 5.342, 95 % CI 4.942-5.777). Cases with the general health outcomes of infection (OR 0.765, 95 % CI 0.428 1.312), conjunctivitis (OR 1.010, 95 % CI 0.480-2.016), diarrhea (OR 0.927, 95 % CI 0.809-1.059), or pneumonia (OR 0.785, 95 % CI 0.481-1.246) were no more likely than controls to have received HPV4 vaccine. Confirmatory epidemiological studies in other databases should be undertaken and long-term clinical consequences of HPV-linked SAAEs should be examined. PMID- 27406736 TI - Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome. AB - Hydroxychloroquine (HCQ) was suggested to play a role in lowering antiphospholipid antibody titers and preventing thrombotic recurrences in patients with systemic lupus erythematosus, but few data are available in patients with primary antiphospholipid syndrome (PAPS). In this retrospective, propensity score-matched cohort study, we evaluated the impact of HCQ on aPL titers and the incidence of thrombotic events in 57 exposed patients compared to 57 not exposed patients. These were matched for sex/type of disease onset/follow up duration, age at the beginning of the follow-up +/-10 years and initial date of the follow-up +/-5 years. At baseline, no significant differences in demographical, clinical and serological features were observed between the two groups except for positive anti-extractable nuclear antigen antibodies (21 % in HCQ exposed vs 0 % in HCQ not exposed, P = 0.001). Both the levels of IgG anti cardiolipin and IgG/IgM anti-beta2-glycoprotein I (anti-beta2GPI) were significantly reduced at end of follow-up compared to the baseline in HCQ-exposed patients, while there were no differences in the other group. Moreover, anti beta2GPI IgG titers were significantly decreased when the end of follow-up was compared between the two groups (P < 0.002). Among patients with a history of thrombosis, the annual incidence of recurrence was 1.16 % in HCQ exposed and 1.71 % in not exposed patients, with a significant reduction in the incidence of arterial events (0 vs 1.14 %). This study shows a strong reduction in aPL titers together with an apparent decrease in the incidence of arterial thrombosis recurrence in PAPS patients treated with HCQ. PMID- 27406737 TI - Two hundreds cases of ASIA syndrome following silicone implants: a comparative study of 30 years and a review of current literature. AB - In this study, we compared one hundred patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone implant incompatibility syndrome diagnosed in 2014 in Maastricht, the Netherlands, with one hundred historical patients with adjuvant breast disease diagnosed in the Baylor College of Medicine, Houston, USA, between 1985 and 1992. Similarities and differences between these two cohorts were identified to determine whether the spectrum of silicone-related disease changed during the last 30 years. Patients with complaints possibly due to silicone-filled breast implants were prospectively examined in the Reinaert Clinic, Maastricht, the Netherlands between January 2014 and October 2014. All patients were evaluated for the fulfilment of ASIA criteria. Results were compared to results of the Baylor College cohort and 18 other reviewed historical cohorts. Clinical manifestations between the Maastricht and Baylor College cohorts were comparable. Fatigue was observed in 98 current patients and in 95 historical patients. Arthralgia was observed in 91 versus 81 historical patients. Myalgia was observed in 54 versus 91 patients. Cognitive impairment was observed in 78 versus 81 patients, pyrexia was observed in 64 versus 52 patients, sicca complaints in 73 versus 72 patients and severe neurological manifestations in 20 versus 32 patients. From the 54 patients who underwent removal of their silicone breast implant, 50 % (n = 27) of the patients experienced improvement of complaints after explantation of the implant. Also, in the 18 reviewed historical cohorts, similar clinical manifestations were described. Our findings suggest that no major changes were present in the observed clinical manifestations between the Maastricht and Baylor College cohorts. Also, despite changes in the principal constituents of the silicone implants during the past fifty years, silicone remained an adjuvant that may 'bleed' and subsequently may be a chronic stimulus to the immune system resulting in similar clinical manifestations as observed in the Maastricht cohort, the Baylor College cohort and 18 other large cohorts of patients. We therefore conclude that silicone-related disease has not changed during the last 30 years. PMID- 27406738 TI - Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents. AB - Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the beta-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates beta-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the beta-cell mechanism that explains the acute, antidiabetic activity of imeglimin. PMID- 27406739 TI - Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis. AB - Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes. Maternal liver and plasma (n = 6-8/group) were collected across 24-h periods (0800, 1200, 1600, 2000, 0000, 0400) from C57Bl/6J mice under isoflurane-nitrous oxide anesthesia prior to and on days 6, 10, 14 and 18 of pregnancy (term = day 19). Hepatic expression of clock genes and glucoregulatory genes was determined by RT-qPCR. Hepatic clock gene expression was substantially altered across pregnancy, most notably in late gestation when the circadian rhythmicity of several clock genes was attenuated (<=64% reduced amplitude on day 18). These changes were associated with a similar decline in rhythmicity of the key glucoregulatory genes Pck1, G6Pase, and Gk, and by day 18, Pck1 was no longer rhythmic. Overall, our data show marked adaptations in the liver clock during mouse pregnancy, changes that may contribute to the altered circadian variation in glucoregulatory genes near term. We propose that the observed reduction of daily oscillations in glucose metabolism ensure a sustained supply of glucose to meet the high demands of fetal growth. PMID- 27406740 TI - Posttranslational modifications and dysfunction of mitochondrial enzymes in human heart failure. AB - Deficiency of energy supply is a major complication contributing to the syndrome of heart failure (HF). Because the concurrent activity profile of mitochondrial bioenergetic enzymes has not been studied collectively in human HF, our aim was to examine the mitochondrial enzyme defects in left ventricular myocardium obtained from explanted end-stage failing hearts. Compared with nonfailing donor hearts, activity rates of complexes I and IV and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase, and aconitase were lower in HF, as determined spectrophotometrically. However, activity rates of complexes II and III and citrate synthase did not differ significantly between the two groups. Protein expression, determined by Western blotting, did not differ between the groups, implying posttranslational perturbation. In the face of diminished total glutathione and coenzyme Q10 levels, oxidative modification was explored as an underlying cause of enzyme dysfunction. Of the three oxidative modifications measured, protein carbonylation was increased significantly by 31% in HF (P < 0.01; n = 18), whereas levels of 4-hydroxynonenal and protein nitration, although elevated, did not differ. Isolation of complexes I and IV and F1FoATP synthase by immunocapture revealed that proteins containing iron-sulphur or heme redox centers were targets of oxidative modification. Energy deficiency in end-stage failing human left ventricle involves impaired activity of key electron transport chain and Krebs cycle enzymes without altered expression of protein levels. Augmented oxidative modification of crucial enzyme subunit structures implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, thus contributing further to reduced bioenergetics in human HF. PMID- 27406741 TI - Defining human insulin-like growth factor I gene regulation. AB - Growth hormone (GH) plays an essential role in controlling somatic growth and in regulating multiple physiological processes in humans and other species. Insulin like growth factor I (IGF-I), a conserved, secreted 70-amino acid peptide, is a critical mediator of many of the biological effects of GH. Previous studies have demonstrated that GH rapidly and potently promotes IGF-I gene expression in rodents and in some other mammals through the transcription factor STAT5b, leading to accumulation of IGF-I mRNAs and production of IGF-I. Despite this progress, very little is known about how GH or other trophic factors control human IGF1 gene expression, in large part because of the absence of any cellular model systems that robustly express IGF-I. Here, we have addressed mechanisms of regulation of human IGF-I by GH after generating cells in which the IGF1 chromosomal locus has been incorporated into a mouse cell line. Using this model, we found that physiological levels of GH rapidly stimulate human IGF1 gene transcription and identify several potential transcriptional enhancers in chromatin that bind STAT5b in a GH-regulated way. Each of the putative enhancers also activates a human IGF1 gene promoter in reconstitution experiments in the presence of the GH receptor, STAT5b, and GH. Thus we have developed a novel experimental platform that now may be used to determine how human IGF1 gene expression is controlled under different physiological and pathological conditions. PMID- 27406742 TI - beta-Cell dedifferentiation, reduced duct cell plasticity, and impaired beta-cell mass regeneration in middle-aged rats. AB - Limitations in beta-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated beta-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. beta-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, beta-cell mass did not change after Px or after gastrin treatment in middle-aged rats. beta-Cell replication and individual beta-cell size were similarly increased after Px in young and middle-aged animals, and beta-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet beta-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory beta-cell hyperplasia and hypertrophy was retained in middle-aged rats, but beta-cell dedifferentiation and impaired duct cell plasticity limited beta-cell regeneration. PMID- 27406743 TI - Robotic ultrasound-guided SBRT of the prostate: feasibility with respect to plan quality. AB - PURPOSE: Advances in radiation therapy delivery systems have enabled motion compensated SBRT of the prostate. A remaining challenge is the integration of fast, non-ionizing volumetric imaging. Recently, robotic ultrasound has been proposed as an intra-fraction image modality. We study the impact of integrating a light-weight robotic arm carrying an ultrasound probe with the CyberKnife system. Particularly, we analyze the effect of different robot poses on the plan quality. METHODS: A method to detect the collision of beams with the robot or the transducer was developed and integrated into our treatment planning system. A safety margin accounts for beam motion and uncertainties. Using strict dose bounds and the objective to maximize target coverage, we generated a total of 7650 treatment plans for five different prostate cases. For each case, ten different poses of the ultrasound robot and transducer were considered. The effect of different sets of beam source positions and different motion margins ranging from 5 to 50 mm was analyzed. RESULTS: Compared to reference plans without the ultrasound robot, the coverage typically drops for all poses. Depending on the patient, the robot pose, and the motion margin, the reduction in coverage may be up to 50 % points. However, for all patient cases, there exist poses for which the loss in coverage was below 1 % point for motion margins of up to 20 mm. In general, there is a positive correlation between the number of treatment beams and the coverage. CONCLUSION: While the blocking of beam directions has a negative effect on the plan quality, the results indicate that a careful choice of the ultrasound robot's pose and a large solid angle covered by beam starting positions can offset this effect. Identifying robot poses that yield acceptable plan quality and allow for intra-fraction ultrasound image guidance, therefore, appears feasible. PMID- 27406744 TI - Reconstituting the Human Immune System. AB - Studying checkpoint blockers and other new immunotherapies is challenging in traditional mouse models because the animals lack B and T cells and have impaired innate immunity. To address these shortcomings, researchers are making progress in reconstituting the human immune system in immunodeficient mouse models. PMID- 27406746 TI - Midfacial involvement in lichen myxedematosus: a clinical pearl in diagnosis. PMID- 27406747 TI - Hypercoagulable State. AB - BACKGROUND: The hypercoagulable state results from a complex interplay of blood coagulation factors, coagulation-inhibitory factors, platelets and the vascular endothelium. Imbalance of the complex interplay between these factors results in thrombosis often complicated by embolism. The causes of thrombosis are varied and maybe congenital or acquired. The current interest is centered on the congenital deficiency of coagulation inhibitors as there is an increasing awareness of their involvement in thrombosis, especially in the young. METHODS: A total of 42 patients with thrombosis were studied. The most common clinical presentation was deep vein thrombosis. All the cases were evaluated for coagulation inhibitors Antithrombin, resistance to activated protein C, Protein C and Protein S using standard assay kits. RESULTS: Resistance to activated protein C (n=10) was seen to be the commonest cause of thrombophilia. This was followed by deficiency of Antithrombin (n-4), Protein C (n=3) and Protein S (n=2). Majority of our cases were in the third decade of life. CONCLUSION: The identification of the underlying aetiology is important for instituting specific therapy and patient management. PMID- 27406745 TI - Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models. AB - The JAK/STAT pathway is an attractive target for breast cancer therapy due to its frequent activation, and clinical trials evaluating JAK inhibitors (JAKi) in advanced breast cancer are ongoing. Using patient biopsies and preclinical models of breast cancer, we demonstrate that the JAK/STAT pathway is active in metastasis. Unexpectedly, blocking the pathway with JAKi enhances the metastatic burden in experimental and orthotopic models of breast cancer metastasis. We demonstrate that this prometastatic effect is due to the immunosuppressive activity of JAKi with ensuing impairment of NK-cell-mediated anti-tumour immunity. Furthermore, we show that immunostimulation with IL-15 overcomes the enhancing effect of JAKi on metastasis formation. Our findings highlight the importance of evaluating the effect of targeted therapy on the tumour environment. The impact of JAKi on NK cells and the potential value of immunostimulators to overcome the weakened tumour immunosurveillance, are worthwhile considering in the clinical setting of breast cancer. PMID- 27406748 TI - [Tuberculosis, a story still relevant]. PMID- 27406749 TI - [Our students are talented!]. PMID- 27406750 TI - [The acoustic niche of screams]. PMID- 27406751 TI - [How bacteria resist to bleach: a new way of repairing oxidized proteins]. PMID- 27406752 TI - [Towards a new paradigm in physiotherapy?]. PMID- 27406753 TI - [A subpopulation of interneurons in the dorsal spinal cord involved in mechanical itch]. PMID- 27406754 TI - [A gene coding for a metalloprotease for the first time implied in heterotaxy]. PMID- 27406755 TI - [Actin and annexin A2: essential partners for the control of neuroendocrine secretion]. PMID- 27406756 TI - [Genetics of schizophrenia: is the complement component 4 a risk factor?]. PMID- 27406757 TI - [PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes]. PMID- 27406758 TI - [A mystery solved: HIV-1 Nef targets SERINC3 and SERINC5]. PMID- 27406759 TI - [Dissemination of prostate cancer: a way paved of fat]. PMID- 27406760 TI - [Hepatitis C, EGFR, cirrhosis and netrin-1: potential implications for HCC onset]. PMID- 27406761 TI - [Unveiling the role of endoplasmic reticulum stress and unfolded protein response in cortical neurogenesis]. PMID- 27406762 TI - [Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects]. PMID- 27406764 TI - [Recent scientific advances in the signalling field under scrutiny by master students (Paris-Saclay university)]. PMID- 27406763 TI - [Rapamycin opens the era of targeted molecular therapy of venous malformations]. PMID- 27406765 TI - [The two-faced Sestrin2 against age-related pathologies]. PMID- 27406766 TI - [Crystal wars: the necroptosis strikes back]. PMID- 27406768 TI - [Mission phagocytosis: how to fit the weapons to the target size]. PMID- 27406767 TI - [Cholangiocyte proliferation induced by bile acids: impact of TGR5]. PMID- 27406769 TI - [Inflammation and muscle regeneration, a double-edged sword]. AB - Muscle injuries are very frequent and are associated with an inflammatory reaction that varies in intensity. Classically the inflammatory process was considered harmful for muscle regeneration and anti-inflammatory agents are still part of a conventional therapy. Over the last decades, it has been demonstrated under some conditions that the inflammatory response could be detrimental for the musculoskeletal tissue. However, accumulating evidence indicate that controlled and efficient inflammatory response is necessary for an optimal muscle recovery. Among the resident and infiltrating leukocytes that participate into the inflammatory process, macrophages play a critical role in muscle regeneration due to their ability to switch from pro-inflammatory to anti-inflammatory phenotypes depending on their microenvironment. The present review synthesizes the recent advances regarding the interactions of the different infiltrating and resident leukocytes on myogenic cell function and muscle regeneration. PMID- 27406770 TI - [Fanconi anemia animal models - How differences can teach us as much as similarities...]. AB - Fanconi Anemia is a rare autosomal recessive genetic disease with heterogenous phenotypes including myelosuppression, congenital malformations and heightened cancer predisposition. FA cells are highly sensitive to cross-linking agents. Since the 90's, at least 19 FANC proteins (FANCA to FANCT) have been identified as working together in a unique pathway detecting and triggering the repair of DNA crosslinks. Since then, the creation of animal models in various species (nematode, fruit fly, zebrafish and mouse) contributed to a better understanding of the physiopathology of the disease. This review aims to summarize the main discoveries made in these in vivo models, as well as to discuss some controversies that arose from these studies. PMID- 27406771 TI - [ManNAc, a new therapeutic agent to reduce Angptl4-induced proteinuria in MCD]. AB - Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD. PMID- 27406772 TI - [Interleukin 2 revival: a revisited model and new therapeutic applications]. AB - Interleukin-2, a cytokine identified as T-cell growth factor, has long been regarded as central to the development and effector activities of immune responses. Several gene knockout mouse studies and observations in humans, however, have undermined that vision, and the discovery of regulatory T cells showed that IL-2, in contrast to the accepted dogma, has the essential function of promoting (1) homeostasis and (2) the function of these T regulator cells the which, limit the action of the effector cells, in particular to prevent the autoimmune reaction drifts. This new paradigm has major implications on the use of IL-2 in therapy, and creates new strategies to manipulate the Teffectors/Tregulators balance. PMID- 27406773 TI - [Impact of opiates on dopaminergic neurons]. AB - Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should however be updated based on recent advances. Thus, the neuroanatomical location of the GABA neurons responsible for this desinhibition has been recently detailed: they belong to a brain structure in continuity with the posterior part of the ventral tegmental area and discovered this past decade. Other data also highlighted the critical role played by glutamatergic transmission in the opioid regulation of dopaminergic neuron activity. During protracted opiate withdrawal, the inhibitory/excitatory balance exerted on dopaminergic neurons is altered. These results are now leading to propose an original hypothesis for explaining the impact of protracted opiate withdrawal on mood. PMID- 27406774 TI - [NO and cancer: itinerary of a double agent]. AB - Protein S-nitrosylation is now recognized as a ubiquitous regulatory mechanism. Like any post-translational modifications, S-nitrosylation is critical for the control of numerous cellular processes. It is now clear that S-nitrosylation is playing a double game, enhancing or inhibiting the tumor growth or the induction of cell death. Thanks to research aimed at demonstrating NO cytotoxic effects, new therapeutic strategies based on NO donor drugs have emerged. Although therapeutic NO donors can target a large number of proteins, the cellular mechanism is still not fully understood. This review reflects the current state of knowledge on S-nitrosylated proteins that take part of the oncogenic and apoptotic signaling, putting forward proteins with potential interest in cancer therapy. PMID- 27406775 TI - [Physics of the radiations and life sciences - The Commissariat a l'energie atomique (CEA) and the biomedical research, a historic overview]. PMID- 27406776 TI - [The CRISPR case, " ready-made " mutations and Lamarckian evolution of an adaptive immunity system]. AB - Since genetics has shown that mutation predates selection, biology has developed within the Darwinian paradigm framework. However, a mechanism that produces favorable mutations preferentially in response to adaptive constraints has been recently identified. This mechanism, the CRISPR-Cas adaptive immunity system, is considered as a bona fide example of Lamarckian evolution, even if it only reflects loosely Lamarck's ideas. This unusual evolutionary process is made possible by two prokaryotic properties: i) somatic and germinal cells are not distinct sets of cells; ii) Archae and Bacteria very frequently integrate DNA fragments from the environment, and they therefore have access to a source of "ready-made" useful genetic information. The CRISPR-Cas is a defense system against viruses and plasmids that is based on the integration of genomic fragments of these infectious agents into the host genome, and that protects the host against subsequent infections. Therefore, this mechanism does produce advantageous mutations by integrating DNA from the environment and allowing its transmission to descendants. In conclusion, most of the time evolution relies on purely Darwinian processes, i.e. mutations occurring at random, but in a small minority of cases the occurrence of mutations is more or less biased, and is therefore more or less Lamarckian. Although they are rare, such processes are nevertheless important to our understanding of the plurality of modes of evolution. PMID- 27406777 TI - [An ideal university? History of the university of Strasbourg from 1919 till 1939 (Francoise Olivier-Utard)]. PMID- 27406778 TI - [Repartee about Philippe Lysy's article]. PMID- 27406779 TI - [Synthetic, really?]. AB - The synthesis of a minimal bacterial genome comprising only 473 genes is an impressive achievement, yet it is only a step towards a really synthetic genome based on first principles: this set of genes was derived from a larger genome by successive elimination of non-essential genes, and 149 of the final 473 genes have no specific (known) biological function. It is nevertheless an important stepping stone towards fully designed minimal genomes. PMID- 27406781 TI - The use of commitment techniques to support weight loss maintenance in obese adolescents. AB - OBJECTIVES: Obesity is a rising problem in adolescents related to unhealthy behaviours. Commitment devises are one type of behavioural intervention that may help people change their behaviours. The current pilot trial tests whether commitment devices delivered via text message help adolescents maintain their recent weight loss. METHODS: During a 12-week pilot trial, adolescents who attended a weight loss camp were randomly assigned to either received text messages that contained only information, i.e. advice, about weight loss management (n = 13) or asked for them to commit to following the same advise (n = 14). RESULTS: The BMI of the adolescents in the commitment group did not change. In contrast, the BMI of adolescents in the information group increased. A linear regression revealed that group was a significant predictor of BMI change. A logistic regression revealed that adolescents in the information group were nearly eight times more likely to regain weight than those in the commitment group. CONCLUSIONS: This is the first study with adolescents to show weight maintenance using a commitment device. The results suggest that commitment devices can help adolescents maintain their recent weight loss. PMID- 27406782 TI - A compendium of temperature responses of Rubisco kinetic traits: variability among and within photosynthetic groups and impacts on photosynthesis modeling. AB - The present study provides a synthesis of the in vitro and in vivo temperature responses of Rubisco Michaelis-Menten constants for CO2 (Kc) and O2 (Ko), specificity factor (Sc,o) and maximum carboxylase turnover rate (kcatc) for 49 species from all the main photosynthetic kingdoms of life. Novel correction routines were developed for in vitro data to remove the effects of study-to-study differences in Rubisco assays. The compilation revealed differences in the energy of activation (?Ha) of Rubisco kinetics between higher plants and other photosynthetic groups, although photosynthetic bacteria and algae were under represented and very few species have been investigated so far. Within plants, the variation in Rubisco temperature responses was related to species' climate and photosynthetic mechanism, with differences in ?Ha for kcatc among C3 plants from cool and warm environments, and in ?Ha for kcatc and Kc among C3 and C4 plants. A negative correlation was observed among ?Ha for Sc/o and species' growth temperature for all data pooled, supporting the convergent adjustment of the temperature sensitivity of Rubisco kinetics to species' thermal history. Simulations of the influence of varying temperature dependences of Rubisco kinetics on Rubisco-limited photosynthesis suggested improved photosynthetic performance of C3 plants from cool habitats at lower temperatures, and C3 plants from warm habitats at higher temperatures, especially at higher CO2 concentration. Thus, variation in Rubisco kinetics for different groups of photosynthetic organisms might need consideration to improve prediction of photosynthesis in future climates. Comparisons between in vitro and in vivo data revealed common trends, but also highlighted a large variability among both types of Rubisco kinetics currently used to simulate photosynthesis, emphasizing the need for more experimental work to fill in the gaps in Rubisco datasets and improve scaling from enzyme kinetics to realized photosynthesis. PMID- 27406783 TI - Fine tuning chloroplast movements through physical interactions between phototropins. AB - Phototropins are plant photoreceptors which regulate numerous responses to blue light, including chloroplast relocation. Weak blue light induces chloroplast accumulation, whereas strong light leads to an avoidance response. Two Arabidopsis phototropins are characterized by different light sensitivities. Under continuous light, both can elicit chloroplast accumulation, but the avoidance response is controlled solely by phot2. As well as continuous light, brief light pulses also induce chloroplast displacements. Pulses of 0.1s and 0.2s of fluence rate saturating the avoidance response lead to transient chloroplast accumulation. Longer pulses (up to 20s) trigger a biphasic response, namely transient avoidance followed by transient accumulation. This work presents a detailed study of transient chloroplast responses in Arabidopsis. Phototropin mutants display altered chloroplast movements as compared with the wild type: phot1 is characterized by weaker responses, while phot2 exhibits enhanced chloroplast accumulation, especially after 0.1s and 0.2s pulses. To determine the cause of these differences, the abundance and phosphorylation levels of both phototropins, as well as the interactions between phototropin molecules are examined. The formation of phototropin homo- and heterocomplexes is the most plausible explanation of the observed phenomena. The physiological consequences of this interplay are discussed, suggesting the universal character of this mechanism that fine-tunes plant reactions to blue light. Additionally, responses in mutants of different protein phosphatase 2A subunits are examined to assess the role of protein phosphorylation in signaling of chloroplast movements. PMID- 27406784 TI - Overexpression of an Arabidopsis cysteine-rich receptor-like protein kinase, CRK5, enhances abscisic acid sensitivity and confers drought tolerance. AB - Receptor-like kinases (RLKs) have been reported to regulate many developmental and defense process, but only a few members have been functionally characterized. In the present study, our observations suggest that one of the RLKs, a membrane localized cysteine-rich receptor-like protein kinase, CRK5, is involved in abscisic acid (ABA) signaling in Arabidopsis thaliana Overexpression of CRK5 increases ABA sensitivity in ABA-induced early seedling growth arrest and promotion of stomatal closure and inhibition of stomatal opening. Interestingly, and importantly, overexpression of CRK5 enhances plant drought tolerance without affecting plant growth at the mature stages and plant productivity. Transgenic lines overexpressing a mutated form of CRK5, CRK5 (K372E) with the change of the 372nd conserved amino acid residue from lysine to glutamic acid in its kinase domain, result in wild-type ABA and drought responses, supporting the role of CRK5 in ABA signaling. The loss-of-function mutation of the CRK5 gene does not affect the ABA response, while overexpression of two homologs of CRK5, CRK4 and CRK19, confers ABA responses, suggesting that these CRK members function redundantly. We further showed that WRKY18, WRKY40 and WRKY60 transcription factors repress the expression of CRK5, and that CRK5 likely functions upstream of ABI2 in ABA signaling. These findings help in understanding the complex ABA signaling network. PMID- 27406785 TI - Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background. AB - Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies. PMID- 27406786 TI - Drooling in Parkinson's disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins. AB - INTRODUCTION: Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD. METHODS: 1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models. RESULTS: 1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm +/- SD: -0.194 +/- 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands. CONCLUSIONS: This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful. PMID- 27406787 TI - Gender-specific uncertainties in the diagnosis of acute coronary syndrome. AB - BACKGROUND: It is unknown whether higher rates of delayed diagnosis and misdiagnosis of acute coronary syndrome (ACS) in women might have contributed to the poorer outcome of women. METHODS: In a prospective diagnostic multicenter study, we recruited patients presenting to the emergency department (ED) with any kind of chest discomfort/chest pain with onset or peak within the last 12 h. We quantified early diagnostic uncertainty for the presence of ACS among treating physicians at the ED after 90 min, possibly responsible for delayed diagnosis, using a visual analogue scale. Late diagnostic uncertainty, possibly responsible for misdiagnosis, was defined as disagreement among two independent cardiologists' adjudication of the final diagnosis after complete work-up. RESULTS: Among 2795 patients (897 women and 1898 men), ACS was the adjudicated final diagnosis in 24 % of women and 35 % of men. Early diagnostic accuracy of clinical judgment of the ED physician for ACS as quantified by the area under the receiver-operating characteristics curve was 0.89 (95 % CI 0.87-0.92) in women and 0.86 (95 % CI 0.85-0.88) in men (p = 0.046). Late diagnostic uncertainty regarding the diagnosis of ACS was 5 % in women and 7 % in men (p = 0.069). CONCLUSION: Diagnostic uncertainty for the presence of ACS in women is not more common as compared to men and does, therefore, not explain the poorer outcome observed in women with ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00470587. PMID- 27406788 TI - Decreased levels of kynurenic acid in prefrontal cortex in a genetic animal model of depression. AB - OBJECTIVE: There is a growing interest in the role of kynurenine pathway and tryptophan metabolites in the pathophysiology of depression. In the present study, the metabolism of tryptophan along the kynurenine pathway was analysed in a rat model of depression. METHODS: Kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were measured by high-performance liquid chromatography (HPLC) in prefrontal cortex (PFC) and frontal cortex (FC) in a rat model of depression, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL) rats. In addition, KYNA was also measured in hippocampus, striatum and cerebellum. RESULTS: KYNA levels were reduced in the PFC of FSL rats compared with FRL rats, but did not differ with regard to the FC, hippocampus, striatum or cerebellum. 3-HK levels in PFC and FC, representing the activity of the microglial branch of the kynurenine pathway, did not differ between the FSL and FRL strains. CONCLUSION: Our results suggest an imbalanced metabolism of the kynurenine pathway in the PFC of FSL rats. PMID- 27406789 TI - Fourth Generation of Next-Generation Sequencing Technologies: Promise and Consequences. AB - In this review, we discuss the emergence of the fourth-generation sequencing technologies that preserve the spatial coordinates of RNA and DNA sequences with up to subcellular resolution, thus enabling back mapping of sequencing reads to the original histological context. This information is used, for example, in two current large-scale projects that aim to unravel the function of the brain. Also in cancer research, fourth-generation sequencing has the potential to revolutionize the field. Cancer Research UK has named "Mapping the molecular and cellular tumor microenvironment in order to define new targets for therapy and prognosis" one of the grand challenges in tumor biology. We discuss the advantages of sequencing nucleic acids directly in fixed cells over traditional next-generation sequencing (NGS) methods, the limitations and challenges that these new methods have to face to become broadly applicable, and the impact that the information generated by the combination of in situ sequencing and NGS methods will have in research and diagnostics. PMID- 27406790 TI - Bacteriocinogenic Potential of Enterococcus faecium Isolated from Wine. AB - A total of 145 lactic acid bacteria isolated from a variety of Turkish red wines during malolactic fermentation were screened to find bacteriocin-producing strains. Among them, 14 isolates of Enterococcus faecium were identified to produce bacteriocins. PCR screening revealed that some isolates harbored entA and entB genes while some harbored entA, entB and entP genes. An isolate designated as Ent. faecium H46 was selected to characterize its bacteriocins. The bacteriocins were purified to homogeneity from culture supernatant by Amberlite XAD-16, cation-exchange and reverse-phase chromatography. MALDI-TOF mass spectrometry analysis identified the bacteriocins as enterocin A and enterocin B. The presence of Ent. faecium is noteworthy since it is not associated with wine fermentation. However, it has been reported as an important wine spoilage organism due to its potential to produce tyramine. Although species of Enterococcus is not known as wine bacteria, contamination by Ent. faecium may arise from grapes or wineries equipments used for wine production. PMID- 27406792 TI - Modelling of an ultra-thin silicatene/silicon-carbide hybrid film. AB - Recently, a well-ordered silicatene/silicon-carbide hybrid thin-film supported on Ru(0 0 0 1) has been reported (2015 Surf. Sci. 632 9-13). The thin-film consist of a monolayer of corner sharing (SiO4)-tetrahedra on top of a (Si2C3) monolayer supported on the Ru(0 0 0 1) surface. This silicatene/silicon-carbide hybrid system may exhibit interesting properties for nano-technological applications and represents another example of a 2D material. We explore the physical and chemical properties of the silicatene/silicon-carbide thin-film using DFT and compare the vibrational spectra with existing experimental data. The characteristics of the silicatene/silicon-carbide hybrid system are compared with those of the bilayer silicatene (pure SiO2 film). We found large differences in the adsorption modes of the two thin-films on the Ru(0 0 0 1) support. Whereas the bilayer-silicatene physisorbs on the Ru(0 0 0 1) surface, the silicatene/silicon-carbide layer binds via chemisorption. The chemical properties of the two thin-films were probed by adsorption of H atoms at various positions, as well as by Al-doping and the formation of hydroxyl groups (Al-OH). These results show that despite the similar structure of the top layer and the identical metal support (Ru), the mixed silicatene/silicon-carbide system behaves quite differently from the pure silica two-layer counterpart. PMID- 27406793 TI - Skermanella rosea sp. nov., isolated from hydrocarbon-contaminated desert sands. AB - A novel Gram-stain-negative, small rod-shaped, motile strain, designated M1T, was isolated from hydrocarbon-contaminated desert sands collected from Kuwait. M1T grew at 12-45 degrees C, pH 6.1-8.8 and 0-4.5 % (w/v) NaCl concentration. Casein, Tween-20 and Tween-80 were hydrolyzed while starch, urea, chitin, DNA and carboxymethyl-cellulose were not hydrolyzed by M1T. C18 : 1omega6c/C18 : 1omega7c, C16 : 0 and C12 : 0 aldehyde were predominant fatty acids with minor amounts of iso-C16 : 1I/C14 : 0 3-OH, C16 : 0 3-OH, C18 : 0, C16 : 1omega6c/C16 : 1omega7c, C16 : 1omega11c and C18 : 1omega9c. Diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were the major polar lipids. Minor amounts of unidentified aminolipids (AL1 2), unidentified phospholipids (PL1-2) and unidentified lipids (L1-4) were also detected. Genomic G+C content was 69.5 mol%. Comparisons of 16S rRNA gene sequence indicate that M1T represent a member of the genus Skermanella in the family Rhodospirillaceae of the class Alphaproteobacteria. M1T has a sequence similarity of 97.5 % with Skermanella aerolata 5416T-32T, 96.7 % with Skermanella stibiiresistens SB22T and <95.7 % with the other two species of the genus Skermanella. DNA-DNA hybridization values between M1T and the type strains of the most closely related species were clearly below the 70 % threshold. Distinct morphological, physiological and genotypic differences from the previously described taxa support the classification of strain M1T as a representative of a novel species in the genus Skermanella, for which the name Skermanella rosea sp. nov. is proposed. The type strain is M1T (=KEMB 2255-458T=JCM 31276T). PMID- 27406791 TI - Coelimination and Survival in Gene Network Evolution: Dismantling the RA Signaling in a Chordate. AB - The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. Outside bacteria and yeast, however, the understanding of the process of gene loss remains elusive, especially in the evolution of animal species. Here, using the dismantling of the retinoic acid metabolic gene network (RA-MGN) in the chordate Oikopleura dioica as a case study, we combine approaches of comparative genomics, phylogenetics, biochemistry, and developmental biology to investigate the mutational robustness associated to biased patterns of gene loss. We demonstrate the absence of alternative pathways for RA-synthesis in O. dioica, which suggests that gene losses of RA-MGN were not compensated by mutational robustness, but occurred in a scenario of regressive evolution. In addition, the lack of drastic phenotypic changes associated to the loss of RA-signaling provides an example of the inverse paradox of Evo-Devo. This work illustrates how the identification of patterns of gene coelimination-in our case five losses (Rdh10, Rdh16, Bco1, Aldh1a, and Cyp26)-is a useful strategy to recognize gene network modules associated to distinct functions. Our work also illustrates how the identification of survival genes helps to recognize neofunctionalization events and ancestral functions. Thus, the survival and extensive duplication of Cco and RdhE2 in O. dioica correlated with the acquisition of complex compartmentalization of expression domains in the digestive system and a process of enzymatic neofunctionalization of the Cco, while the surviving Aldh8 could be related to its ancestral housekeeping role against toxic aldehydes. PMID- 27406794 TI - Synthesis and antibacterial evaluation of macrocyclic diarylheptanoid derivatives. AB - Bacterial infections, caused by Mycobacterium tuberculosis and other problematic bacterial pathogens, continue to pose a significant threat to global public health. As such, new chemotype antibacterial agents are desperately needed to fuel and strengthen the antibacterial drug discovery and development pipeline. As part of our antibacterial research program to develop natural product-inspired new antibacterial agents, here we report synthesis, antibacterial evaluation, and structure-activity relationship studies of an extended chemical library of macrocyclic diarylheptanoids with diverse amine, amide, urea, and sulfonamide functionalities. Results of this study have produced macrocyclic geranylamine and 4-fluorophenethylamine substituted derivatives, exhibiting moderate to good activity against M. tuberculosis and selected Gram-positive bacterial pathogens. PMID- 27406795 TI - Discovery of 2-((3-cyanopyridin-2-yl)thio)acetamides as human lactate dehydrogenase A inhibitors to reduce the growth of MG-63 osteosarcoma cells: Virtual screening and biological validation. AB - Lactate dehydrogenase A (LDHA) has emerged as an attractive target in the oncology field. In this paper, we present the identification of 2-((3 cyanopyridin-2-yl)thio)acetamide-containing compounds as LDHA inhibitors. The in vitro enzymatic assay suggested that inhibitor 9 had good inhibitory potency against LDHA with IC50 value as 1.24MUM. Cytotoxicity assay showed that inhibitor 9 strongly inhibited the proliferation of cancer cell MG-63 (EC50=0.98MUM). These findings indicated that inhibitor 9 could be employed as a lead for developing more potent LDHA inhibitor with anti-proliferative potency. PMID- 27406796 TI - Synthesis of benzimidazole based thiadiazole and carbohydrazide conjugates as glycogen synthase kinase-3beta inhibitors with anti-depressant activity. AB - A series of benzimidazole based thiadiazole and carbohydrazide conjugates have been synthesized and evaluated for inhibition of glycogen synthase kinase-3beta and anti-depressant effect. Compounds 4f, 4j, 5b, 5g and 5i were found to be the most potent inhibitors of GSK-3beta in vitro amongst the twenty-five benzimidazole based thiadiazole and carbohydrazide conjugates synthesized. Compound 5i was also found to exhibit significant antidepressant activity in vivo at 50mg/kg, when compared to fluoxetine, a known antidepressant drug. The molecular docking studies revealed multiple hydrogen bond interactions by the synthesized compounds with various amino acid residues, viz, ASP-133, LYS-183, PRO-136, VAL-135, TYR-134, or LYS-60 at the GSK-3beta receptor site. PMID- 27406797 TI - Ionic liquid-promoted multicomponent synthesis of fused tetrazolo[1,5 a]pyrimidines as alpha-glucosidase inhibitors. AB - A simple and facile synthesis of fused tetrazolo[1,5-a]pyrimidine derivatives based on the multicomponent reaction of acetophenone, dimethylformamidedimethylacetal and 5-aminotetrazole is described. A green chemical synthesis has been achieved by using1-butyl-3-methylimidazolium hydrogen sulfate [Bmim]HSO4 ionic liquid as a reusable medium. Short synthetic route, operational simplicity, good yields, eco-friendliness and recyclability of the ionic liquid are the advantages of this method. The synthesized compounds were screened for alpha-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Inhibition and kinetic studies have shown that compounds 4d and 4g are found to be active showing comparable inhibitory potency with acarbose. Further docking studies of the derivatives with MAL12 homology model identified a similar binding mode consistent with the binding of acarbose. These studies along with in silico predicted ADMET properties suggest that these molecules could represent a new scaffold that may be useful for the development of new anti diabetic drugs. PMID- 27406799 TI - The Management of Essential Thrombocythaemia. AB - Essential thrombocythemia (ET) is a clonal myeloproliferative disorder with a relatively benign clinical course and long survival in most patients. The major cause of mortality and morbidity are thromboembolic complications, which occur more frequently in older subjects or in those with a previous thrombosis. The therapeutic options comprise cytoreductive agents (cytotoxic drugs, interferon, anagrelide) and anti-aggregating drugs. In clinical practice the choice of treatment primarily takes into account the patient's age, history and symptoms. The use of platelet-lowering agents is indicated in patients above 60 years and in those with a history of thrombosis or major bleeding, or very high platelet count (e.g. >1,000 X 10(9)/1). Hydroxyurea has emerged as the treatment of choice after the recent demonstration of its efficacy in reducing not only the platelet count but also thromboembolic complications. Low-dose aspirin may be added in the presence of thrombosis or microvascular disturbances. In younger, asymptomatic patients, an initial policy of observation, without specific treatment, or with only low-dose antiaggregating agents seems reasonable. Doubt about the risk of leukaemia transformation associated with hydroxyurea suggests that the use of interferon or anagrelide should be explored. PMID- 27406798 TI - Lead optimization of a pyrazolo[1,5-a]pyrimidin-7(4H)-one scaffold to identify potent, selective and orally bioavailable KDM5 inhibitors suitable for in vivo biological studies. AB - Starting with a lead [1,5-a]pyrimidin-7(4H)-one-containing molecule (1), we generated potent, selective and orally bioavailable KDM5 inhibitors. Using structure- and property-based approaches, we designed 48 with improved cell potency (PC9 H3K4Me3 EC50=0.34MUM). Furthermore, 48 maintained suitable physiochemical properties and displayed an excellent pharmacokinetic (PK) profile in mice. When dosed orally in mice at 50mg/kg twice a day (BID), 48 showed an unbound maximal plasma concentration (Cmax) >15-fold over its cell EC50, thereby providing a robust chemical probe for studying KDM5 biological functions in vivo. PMID- 27406800 TI - Telomeres, Telomerase and Leukaemia. AB - There is increasing evidence supporting the hypothesis that telomere shortening both in vitro and in vivo is the clock that counts cell divisions and determines the onset of cellular senescence. Cells overcome the senescence mechanisms by stabilising telomere length, probably due to the activity of telomerase that specifically elongates telomeres. The striking observation that almost all malignant cancers have telomerase activity indicate that there is intensive selective pressure of telomerase activation with the progression of malignancy. Indirect support for this view is that benign or pre-cancerous lesions are telomerase silent. The fact that telomerase activity is observed in over 85% of human primary malignancies raises the possibilities that it may be a new marker of cancer with diagnostic and therapeutic potentials. Can such ideas be applied to leukaemias and preleukaemias? Since normal haematopoietic stem cells and their progeny express telomerase activity, it is important to consider whether or not telomere shortening and telomerase activity play any role in leukaemic progression. Telomere reduction has been observed in various leukaemias including in ALL, AML, transformed leukaemias from MDS and late stage of CML and CLL and might be indicative of the length of the disease. Elevated telomerase activity has also been found in ALL, AML, CML and CLL. In AML, patients with chromosomal abnormalities 11q, -5, -7 had higher telomerase activity and unfavourable prognosis; while those with favourable cytogenetics such as t(8:21), inversion 16 showed low levels of telomerase. This suggests that telomerase activity may be a marker for poor prognosis of AML. Unanswered at present is the potential role of telomeres and telomerase in the progression of benign to malignant tumours. Further studies on the expression and regulation of the individual components of telomerase may enable us to clarify the diagnostic and therapeutic potential of telomerase in leukaemias. PMID- 27406801 TI - Serum Levels of Soluble CD 30 and Their Relationship to Tumour Burden and Prognosis in Patients with Hodgkin's Disease. AB - PURPOSE: The purpose of the present study was to examine the relationship between the serum levels of soluble CD 30 (S-sCD 30), the Hodgkin and Reed Sternberg (HRS) cell density and the macroscopic tumour burden in untreated patients with Hodgkin's disease (HD). MATERIALS AND METHODS: In 126 untreated patients with HD diagnosed between 1979-1991, (79 males and 47 females, median age 33 years) S-sCD 30 was measured using frozen serum samples. The number of HRS cells (the HRS cell density) was counted in 10 high-power vision fields. The macroscopic tumour volume was estimated in 70 patients in stages I and II by counting the number of involved sites and scoring them according to size. RESULTS: Soluble CD 30 was detected in the sera of all patients. The levels were significantly higher in patients with high HRS cell density, high macroscopic tumour burden, stages III IV, B symptoms and bulky disease. Patients with high S-sCD 30 had a significantly poorer DFS (p < 0.05) and survival (p < 0.001). High HRS cell density correlated to large macroscopic tumour burden, stage IV disease and B-symptoms. Patients with the highest HRS cell density had a significantly poorer disease-free survival (DFS) (p < 0.01) and survival (p < 0.01). In a multivariate analysis, S sCD 30 was more important as regards prognosis than HRS cell density. CONCLUSIONS: Serum levels of sCD 30 are probably a measurement of tumour burden in HD and are also strongly related to the prognosis. A high number of HRS cells correlated to an extensive spread HD and also to prognosis. PMID- 27406802 TI - Comparison of Rai and Binet Classifications in Chronic Lymphocytic Leukemia. AB - Staging systems are essential for understanding disease, in predicting the outcome, and therapeutic decision making in any tumor as well as chronic lymphocytic leukemia (CLL). In this study, we compared the clinical correlation of the Rai and Binet classification systems in 133 CLL patients. The distribution of 133 patients according to the Rai system was as follows, stage 0:17, I:13, II:45, III:30, IV:28, and in the Binet system stage A:35, B:40, C:58 patients. Median survival of patients according to the Rai staging system was >67.0, >91.0, 63.8, 20.9 and 9.8 months, and >91.0, 63.4, 16.0 months according to Binet, respectively. Although no difference was found between Rai stages 0, I, II (p > 0.05) in terms of median survival, the difference between these stages and stages III and IV was statistically significant (p < 0.05). In the Binet staging system statistically significant survival difference was found between all stages (p < 0.05). We concluded that although both systems are comparable in terms of staging and predicting the outcome of patients with CLL, the Rai staging system appears to have an advantage over the Binet system by defining a subset of patients with excellent prognosis (stage 0) which is included within stage A of the latter. PMID- 27406803 TI - Susceptibility to Infection Due to Diminished Interferon-alpha-Producing Capacity in Patients with Refractory Anemia with Excess of Blasts or Refractory Anemia with Excess of Blasts in Transformation. AB - Peripheral whole blood cells from normal subjects and from 8 patients with refractory anemia with excess of blasts (RAEB) and one patient with RAEB in transformation (RAEB-t) were studied to ascertain their interferon (IFN)-alpha producing capacity. This capacity was determined by time-resolved immuno fluoroassay 20 hrs after the blood cells had been incubated with 500 HA/ml of Sendai virus. The mean IFN-alpha-producing capacity in the peripheral whole blood cells of 35 normal males was 8718 +/- 4683 IU/ml, while that of 49 normal females was 7549 +/- 4731 IU/ml; not a significant difference. All of the RAEB and RAEB-t patients examined showed a significantly low (<2500 IU/ml) IFN-alpha-producing capacity in the peripheral whole blood cells. In addition, the levels of IFN alpha-producing capacity in 1 ml cell suspension containing 1 x 10(6) peripheral mononuclear blood cells were markedly lower in all 5 RAEB patients and the RAEB-t patient examined than those in the normal subjects, when 5 HA of Sendai virus was used. The activities of natural killers were lower in the RAEB/RAEB-t patients than those in the normal subjects. These findings suggest that IFN-alpha producing capacity is diminished in the peripheral whole blood cells of RAEB and RAEB-t patients, and great care is advised regarding infection by virus and bacteria in treatment of these patients. PMID- 27406804 TI - Coexistence of Polycythaemia Vera with Indolent Myeloma in the same Patient. AB - We describe a patient with polycythaemia vera, who in the course of investigations for polycythaemia was also found to have multiple myeloma. A 75 year old Caucasian male was refered for investigations of a raised haemoglobin from a dermatology clinic. He was attending dermatology clinic for intractable, generalised pruritus for 6 months. Initial investigations confirmed the diagnosis of primary proliferative polycythaemia. Further examination of the bone marrow and trephine bone biopsy revealed an increase in plasma cells with morphological atypia. Serum protein electrophoresis confirmed a monoclonal band and urinary examination revealed excretion of Bence Jones proteins. Immunoperoxidase stains of the trephine biopsy confirmed monoclonal light chain restriction. Coexistence of polycythaemia vera and multiple myeloma is an extremely rare situation. PMID- 27406805 TI - Role of Soluble Interleukin-6 Receptor With Interleukin-6 in Human Hematopoiesis. AB - A complex of soluble interleukin-6 receptor (sIL-6R) and interleukin-6 has been shown to play some roles in human hematopoiesis. It activates gp130 signal to stimulate human erythroid, megakaryocytic and primitive hematopoietic progenitor cells, which express gp130 but not IL-6R, in the presence of c-Kit signal mediated by stem cell factor (SCF). The culture system using a combination of sIL 6R, IL-6 and SCF can be useful for ex vivo expansion of human hematopoietic stem/progenitor cells and provide a novel way for gene transfer into human hematopoietic stem cells. PMID- 27406806 TI - Endogenous Erythropoietin, Tumor Necrosis Factor-alpha and Interleukin-6 Levels after Peripheral Blood Stem Cell Transplantation. AB - We investigated the kinetics of plasma concentrations of endogenous erythropoietin (EPO), tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) in patients with metastatic breast cancer who received high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) followed by an administration of recombinant human granulocyte-colony-stimulating factor (rhG-CSF). The plasma levels of these cytokines increased significantly after PBSCT and peak levels were observed on day 6 (median) for EPO, day 14.5 for TNF and day 6 for IL-6. EPO levels inversely correlated with hemoglobin levels (p = 0.0207) but no correlation was found between neutrophil recovery and levels of the cytokines tested. The concentrations of TNF and IL-6 directly correlated with body temperature (p = 0.0470 and <0.0001). The maximum level of IL-6 which occurred within 10 days after PBSCT directly correlated with number of days to achieve a platelet count of >20 X 10(9)/1 (p = 0.0003) and number of platelet transfusions (p = 0.0107), suggesting that the high concentrations of IL-6 could be associated with delayed platelet recovery. PMID- 27406807 TI - Identification of Patients with Storage Pool Deficiency Using ATP Release and Dense Granule Counts. AB - Recent reports have suggested that a significant number of patients with long bleeding times and normal platelet aggregation have storage pool deficiency (SPD). The present study screened 215 patients referred for evaluation of haemostasis because of a clinical bleeding history. SPD was identified by the presence of combined abnormalities in platelet ATP release and electron microscopic dense granule enumeration. Eight percent (17/215) of the patients studied were found to have SPD. Eleven percent (9/80) of patients with prolonged bleeding times had SPD, compared to 6% (8/135) of those with normal bleeding times. Two patients were identified as having both SPD and von Willebrand Disease. Although 12 of 17 SPD patients had prolonged bleeding times and/or abnormal platelet aggregation studies, five patients had neither abnormality and would not have been identified without the more specific tests for dense granule number and function. PMID- 27406808 TI - Skin Necrosis Associated With Heparin-Induced Thrombocytopenia and Thrombosis. AB - Skin necrosis is a rare complication of heparin therapy. Strong evidence suggests an immune-mediated mechanism in which heparin-antibody complexes bind to platelets, resulting in platelet aggregation, thromboembolism, and ischemic necrosis. Heparin-induced thrombocytopenia (HIT) may also occur in response to immune-mediated platelet aggregation. The presence, of heparin-dependent antibodies can be confirmed by platelet aggregometry, (14)C-serotonin release assay (SRA), or enzyme-linked immunosorbent assay (ELISA). Clinical suspicion, early detection and immediate cessation of heparin therapy are important in preventing the potentially severe complications of heparin-induced platelet aggregation. Potential therapeutic approaches include plasmapheresis and alternative forms of anticoagulation such as warfarin, aspirin, dipyridamole, or other novel investigational agents. PMID- 27406809 TI - Owen Stuart Roath (1929-1997). PMID- 27406811 TI - Digital pathology imaging offers more benefits than glass slides and microscopes. PMID- 27406810 TI - Orchestration of gene expression across the seasons: Hypothalamic gene expression in natural photoperiod throughout the year in the Siberian hamster. AB - In nature Siberian hamsters utilize the decrement in day length following the summer solstice to implement physiological adaptations in anticipation of the forthcoming winter, but also exploit an intrinsic interval timer to initiate physiological recrudescence following the winter solstice. However, information is lacking on the temporal dynamics in natural photoperiod of photoperiodically regulated genes and their relationship to physiological adaptations. To address this, male Siberian hamsters born and maintained outdoors were sampled every month over the course of one year. As key elements of the response to photoperiod, thyroid hormone signalling components were assessed in the hypothalamus. From maximum around the summer solstice (late-June), Dio2 expression rapidly declined in advance of physiological adaptations. This was followed by a rapid increase in Mct8 expression (T3/T4 transport), peaking early September before gradually declining to minimum expression by the following June. Dio3 showed a transient peak of expression beginning late-August. A recrudescence of testes and body mass occurred from mid-February, but Dio2 expression remained low until late-April of the following year, converging with the time of year when responsiveness to short-day length is re-established. Other photoperiodically regulated genes show temporal regulation, but of note is a transient peak in Gpr50 around late-July. PMID- 27406812 TI - Ruthenium(II) polypyridyl complexes with hydrophobic ancillary ligand as Abeta aggregation inhibitors. AB - The synthesis, spectral and electrochemical characterization of the complexes of the type [Ru(NN)2(txbg)](2+) where NN is 2,2'-bipyridine (bpy) (1), 1,10 phenanthroline (phen) (2), dipyrido [3,2-d:2',3f] quinoxaline (dpq) (3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4) which incorporate the tetra-xylene bipyridine glycoluril (txbg) as the ancillary ligand are described in detail. Crystal structures of ligand txbg and complex 2 were solved by single crystal X ray diffraction. Thioflavin T (ThT) fluorescence and Transmission Electron Microscopy (TEM) results indicated that at micromolar concentration all complexes exhibit significant potential of Abeta aggregation inhibition, while the ligand txbg displayed weak activity towards Abeta aggregation. Complex 1 showed relatively low inhibition (70%) while complexes 2-4 inhibited nearly 100% Abeta aggregation after 240 h of incubation. The similar potential of complexes 2-4 and absence of any trend in their activity with the planarity of polypyridyl ligands suggests there is no marked effect of planarity of coligands on their inhibitory potential. Further studies on acetylcholinesterase (AChE) inhibition indicated very weak activity of these complexes against AChE. Detailed interactions of Abeta with both ligand and complex 2 have been studied by molecular modeling. Complex 2 showed interactions involving all three polypyridyl ligands with hydrophobic region of Abeta. Furthermore, the toxicity of these complexes towards human neuroblastoma cells was evaluated by MTT assay and except complex 4, the complexes displayed very low toxicity. PMID- 27406813 TI - Study of switching in spin transition compounds within the mechanoelastic model with realistic parameters. AB - Here we reproduce the static and dynamical properties of spin-crossover complexes in the framework of the mechanoelastic model applied to triangular lattices. The switching processes between the high-spin and low-spin states are studied by combining the Monte Carlo method with the elastic lattice relaxation. The transition probabilities between the two states take into account intrinsic parameters, the values of which are approximated from experimental quantities (e.g., the energy gap, and the degeneracy ratio from the thermodynamic enthalpy and the entropy difference between the states), and the elastic force or elastic energy stored in the springs connecting the spin-changing centres. The value of the corresponding spring constant is estimated from the experimentally determined variation of the ligand-field strengths in the two spin states due to the cooperativity and the bulk modulus. Both simulated hysteresis loops and relaxation curves are in agreement with experimental data. Cooperativity related phenomena such as like-spin domain formation and the evolution of the interaction distribution with the HS fraction are also analysed. PMID- 27406814 TI - Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes. AB - AIMS/HYPOTHESIS: Identification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction. METHODS: In this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n = 855). Assessment of the association of metabolite regulating genetic variants with type 2 diabetes was done using data from a meta analysis of genome-wide association studies. RESULTS: Out of 5961 investigated metabolic features, 1120 were associated with prevalent type 2 diabetes and IFG and 70 were annotated to metabolites and replicated in the three cohorts. Fifteen metabolites were associated with incident type 2 diabetes in the four cohorts combined (358 events) following adjustment for age, sex, BMI, waist circumference and fasting glucose. Novel findings included associations of higher values of the bile acid deoxycholic acid and monoacylglyceride 18:2 and lower concentrations of cortisol with type 2 diabetes risk. However, adding metabolites to an existing risk score improved model fit only marginally. A genetic variant within the CYP7A1 locus, encoding the rate-limiting enzyme in bile acid synthesis, was found to be associated with lower concentrations of deoxycholic acid, higher concentrations of LDL-cholesterol and lower type 2 diabetes risk. Variants in or near SGPP1, GCKR and FADS1/2 were associated with diabetes-associated phospholipids and type 2 diabetes. CONCLUSIONS/INTERPRETATION: We found evidence that the metabolism of bile acids and phospholipids shares some common genetic origin with type 2 diabetes. ACCESS TO RESEARCH MATERIALS: Metabolomics data have been deposited in the Metabolights database, with accession numbers MTBLS93 (TwinGene), MTBLS124 (ULSAM) and MTBLS90 (PIVUS). PMID- 27406815 TI - Placental endoplasmic reticulum stress in gestational diabetes: the potential for therapeutic intervention with chemical chaperones and antioxidants. AB - AIMS/HYPOTHESIS: The aim of this work was to determine whether placental endoplasmic reticulum (ER) stress may contribute to the pathophysiology of gestational diabetes mellitus (GDM) and to test the efficacy of chemical chaperones and antioxidant vitamins in ameliorating that stress in a trophoblast like cell line in vitro. METHODS: Placental samples were obtained from women suffering from GDM and from normoglycaemic controls and were frozen immediately. Women with GDM had 2 h serum glucose levels > 9.0 mmol/l following a 75 g oral glucose tolerance test and were treated with diet and insulin when necessary. Western blotting was used to assess markers of ER stress. To test the effects of hyperglycaemia on the generation of ER stress, a new trophoblast-like cell line, BeWo-NG, was generated by culturing in a physiological glucose concentration of 5.5 mmol/l (over 20 passages) before challenging with 10 or 20 mmol/l glucose. RESULTS: All GDM patients were well-controlled (HbA1c 5.86 +/- 0.55% or 40.64 +/- 5.85 mmol/mol, n = 11). Low-grade ER stress was observed in the placental samples, with dilation of ER cisternae and increased phosphorylation of eukaryotic initiation factor 2 subunit alpha. Challenge of BeWo-NG with high glucose activated the same pathways, but this was as a result of acidosis of the culture medium rather than the glucose concentration per se. Addition of chemical chaperones 4-phenylbutyrate and tauroursodeoxycholic acid and vitamins C and E ameliorated the ER stress. CONCLUSIONS/INTERPRETATION: This is the first report of placental ER stress in GDM patients. Chemical chaperones and antioxidant vitamins represent potential therapeutic interventions for GDM. PMID- 27406816 TI - Simvastatin Therapy in the Acute Stage of Traumatic Brain Injury Attenuates Brain Trauma-Induced Depression-Like Behavior in Rats by Reducing Neuroinflammation in the Hippocampus. AB - BACKGROUND: The antidepressant-like effects of simvastatin on traumatic brain injury (TBI) remain unclear. The present study aimed to investigate the neuroprotective effects of simvastatin and determine whether simvastatin attenuates TBI-induced depression-like behavior and, more specifically, acts as an antineuroinflammatory. METHODS: Anesthetized male Sprague-Dawley rats were divided into five groups: sham-operated controls, TBI controls, and TBI treatment with simvastatin 4, 10, or 20 mg/kg. Simvastatin was intraperitoneally injected 0, 24, and 48 h after TBI. The motor function was measured using an inclined plane, and depression-like behavior was evaluated using forced swimming tests. Neuronal apoptosis (markers: NeuN, TUNEL, caspase-3), microglia (marker: OX42) and astrocyte (marker: GFAP) activation, and TNF-alpha expression in the microglia and astrocytes of the hippocampal CA3 area were investigated using immunofluorescence assay. All parameters were measured on the 4th, 8th, and 15th day, or only on the 15th day after TBI. RESULTS: TBI-induced depression-like behavior, which increased duration of immobility, was significantly attenuated by 20 mg simvastatin therapy on day 15 after TBI. TBI-induced neuronal apoptosis, microglia and astrocyte activation, and TNF-alpha expression in the microglia and astrocytes of the CA3 area of the hippocampus were significantly reduced by simvastatin treatment, particularly when 20 mg/kg was administered for 3 days. CONCLUSIONS: Intraperitoneal injection of simvastatin attenuated TBI in rats during the acute stage by reducing neuronal apoptosis, microglia, and TNF-alpha expression, thereby resulting in a reduction of depressive-like behavior. Our results suggest that simvastatin may be a promising treatment for TBI-induced depression-like behavior. PMID- 27406818 TI - EEG Characteristics of Successful Burst Suppression for Refractory Status Epilepticus. AB - BACKGROUND: Refractory status epilepticus (RSE) is often treated with continuous intravenous medications with the goal of EEG burst suppression. Standard advice is to titrate medications to at least 10-s interburst intervals; however, this has not been shown to improve outcome. We examined EEG characteristics in patients treated with IV anesthetic therapy (IVAT) for RSE to determine which EEG characteristics were associated with successful lifting of IVAT (i.e., without recurrence of status epilepticus). METHODS: We screened the clinical continuous EEG database for adult patients treated with IVAT for RSE (excluding patients with anoxic injury). We measured the length of bursts and interburst intervals for each patient, calculated EEG burst suppression ratios, and graded bursts for the amount of epileptiform activity. We compared these characteristics in successful versus unsuccessful IVAT lifting attempts. RESULTS: We included 17 successful and 20 unsuccessful lifting attempts in 19 patients (5 used as a holdout validation set). The interburst intervals, burst suppression ratios, and length of bursts did not differentiate successful and unsuccessful lifting attempts; the amount of epileptiform activity in bursts correlated with success or failure to wean IVAT (p = 0.008). Maximum burst amplitude <125 MUV had 84.6 % sensitivity and 61.1 % specificity for predicting successful lifting. CONCLUSION: The length of interburst intervals and burst suppression did not predict successful termination of RSE in this small cohort. This may suggest that EEG characteristics, rather a strict interburst interval goal, could guide IVAT for RSE. PMID- 27406817 TI - Patient Age and the Outcomes after Decompressive Hemicraniectomy for Stroke: A Nationwide Inpatient Sample Analysis. AB - BACKGROUND: Decompressive hemicraniectomy (DHC) for space-occupying cerebral infarction in older adults remains controversial, and there are limited nationwide data evaluating the outcomes after craniectomy for stroke by patient age. METHODS: Patients who underwent DHC for ischemic stroke were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable logistic regression examined in-hospital mortality and a poor outcome (death, tracheostomy and gastrostomy, or discharge to institutional care). Covariates included year of admission, comorbidities, severity indices, and treatment variables (including the timing of decompression). RESULTS: Craniectomy was performed in 1673 patients: 62.4 % were aged 18-60 years, 20.6 % aged 61-70 years, and 17.0 % aged greater than 70 years. DHC was associated with reduced adjusted odds of in hospital death compared with medical treatment alone among patients with cerebral edema in all age categories, including those older than 70 years (p <= 0.008). However, among surgical patients, the adjusted odds of mortality were significantly greater for patients aged 61-70 (30.7 %, p = 0.02) and greater than 70 years (34.5 %, p = 0.02), but not different for patients aged 51-60 (22.8 %), compared to those aged 18-50 years (19.7 %). The adjusted odds of a poor outcome also increased significantly with age, particularly for patients greater than 60 years. CONCLUSION: In this nationwide analysis, DHC was associated with reduced mortality regardless of patient age, including among those aged greater than 70 years. However, patients aged greater than 60 years treated surgically experienced higher odds of mortality (32.4 %), discharge to institutional care (47.1 %), and a poor outcome (77.0 %) compared with younger patients. PMID- 27406819 TI - Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors. AB - Natural killer (NK) cells are critical players against tumors. The outcome of anti-tumor vaccination protocols depends on the efficiency of NK-cell activation, and efforts are constantly made to manipulate them for immunotherapeutic approaches. Thus, a better understanding of NK-cell activation dynamics is needed. NK-cell interactions with accessory cells and trafficking between secondary lymphoid organs and tumoral tissues remain poorly characterized. Here, we show that upon triggering innate immunity with lipopolysaccharide (LPS), NK cells are transiently activated, leave the lymph node, and infiltrate the tumor, delaying its growth. Interestingly, NK cells are not actively recruited at the draining lymph node early after LPS administration, but continue their regular homeostatic turnover. Therefore, NK cells resident in the lymph node at the time of LPS administration become activated and exert anti-tumor functions. NK-cell activation correlates with the establishment of prolonged interactions with dendritic cells (DCs) in lymph nodes, as observed by two-photon microscopy. Close DC and NK-cell contacts are essential for the localized delivery of DC-derived IL 18 to NK cells, a strict requirement in NK-cell activation. PMID- 27406821 TI - How do we measure up? A comparison of lifestyle-related health risk factors among sampled employees in South African and UK companies. AB - The need to address the growing prevalence of non-communicable diseases through changing the lifestyle behaviours that contribute to them has become a global priority. Settings-based health promotion strategies such as workplace health promotion programmes are growing in an attempt to start meeting this need. In order for settings-based health promotion programmes to be successful, they need to be based on the specific risk profiles of the population for whom they are designed. Workplace health promotion programmes are becoming popular in South Africa, but there are currently few data available about the health risks and lifestyle behaviours of the South African employed population. In order to obtain such data and reward workplace health promotion initiatives, Discovery Health initiated healthy company campaigns in South Africa and the UK. These campaigns took the form of a competition to assess the healthiest companies in each country. Through these campaigns, an extensive data set was collected encompassing UK and South African employees' lifestyle behaviours and health risks. In this article, we used these data to compare self-reported physical activity levels, self-reported fruit and vegetable consumption, calculated BMI, self-reported smoking, mental health indicators, and health screening status of the UK and South African employee samples. We found significant differences across all measures, with the exception of self-reported fruit and vegetable consumption. The findings emphasise the importance of using local data to tailor workplace health promotion programmes for the population for which the programmes have been designed. PMID- 27406820 TI - Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake. AB - The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in intracellular membranes. We developed an oligonucleotide that promotes exon inclusion, which increases the ratio of the full-length to truncated receptor protein. Decreasing the amount of truncated receptor results in the accumulation of full-length, constitutively active receptor at the cell surface. After injection into the third ventricle of mice, the oligonucleotide accumulates in the arcuate nucleus, where it changes alternative splicing of the serotonin 2C receptor and increases pro-opiomelanocortin expression. Oligonucleotide injection reduced food intake in both wild-type and ob/ob mice. Unexpectedly, the oligonucleotide crossed the blood-brain barrier and its systemic delivery reduced food intake in wild-type mice. The physiological effect of the oligonucleotide suggests that a truncated splice variant regulates the activity of the serotonin 2C receptor, indicating that therapies aimed to change pre-mRNA processing could be useful to treat hyperphagia, characteristic for disorders like Prader-Willi syndrome. PMID- 27406822 TI - Challenges of being new to Canada: considerations for physical activity. AB - Immigrants to Canada are less likely to be physically active compared with non immigrants, and the interrelations between personal and environmental factors that influence physical activity for immigrants are largely unexplored. The goal of this qualitative descriptive study was to understand how the experience of being new to Canada impacts opportunities and participation in physical activity. Two focus group interviews with immigrants to Canada were conducted. The first group ( n=7) included multicultural health brokers. The second group ( n=14) included English as a second language students. Qualitative content analysis was used to determine three themes consistent with the research question: transition to Canadian life, commitments and priorities, and accessibility. Discussion was framed using a social ecological model. Implications for practice and policy are suggested including enhanced community engagement, and organizational modifications. Overall, the development and implementation of physical activity policies and practices for newcomers to Canada should be centered on newcomers' perspectives and experiences. PMID- 27406823 TI - Factors influencing medication label viewing in Malaysia. AB - The misuse of medicine is a serious public health issue worldwide. An important factor that contributes to the misuse of medicine is the lack of medication label viewing by consumers. The objective of the present study is to examine the socio economic, demographic and lifestyle factors associated with medication label viewing among Malaysian adults. The empirical analysis is based on a nationally representative data set of 30,992 respondents. An ordered probit model is used to examine different types of medication label viewers. The results of this study suggest that socio-economic (i.e. age, income level, education level, location of residence), demographic (i.e. gender, ethnicity, marital status) and lifestyle factors (i.e. physical activity, smoking) have significant effects on medication label viewing. It is found that age, low-income and low-education level reduce the likelihood of viewing medication label. Based on these findings, several policy implications are suggested. The present study provides policy makers with baseline information regarding which cohorts of individuals to focus on in efforts to increase the frequency of medication label viewing. PMID- 27406824 TI - Development and Testing of the Partnership Scale for Primary Family Caregivers Caring for Patients With Dementia. AB - This article reports the development and preliminary testing of a new scale named "Partnership Scale for Primary Family Caregivers Caring for Patients With Dementia" that measures the ability of primary family caregivers to establish partnerships while providing care for patients with dementia in Japan. The first draft of the scale was developed using qualitative data from interviews with five primary family caregivers; a pool of 39 items was created through a review process with dementia care experts and researchers. An exploratory factor analysis and confirmatory factor analysis were conducted with data from 261 primary family caregivers who completed the instrument. This resulted in a multidimensional scale that consists of three factors with 13 items. The suitability of the model and intraclass correlation coefficient (ICC) values (1, 1) obtained by the test-retest method satisfied statistical standards. The criterion-related validity of the scale was significantly correlated to an external reference, which was the desired outcome. However, some subscales exhibited low internal consistency, demonstrating the need for further research. PMID- 27406825 TI - Precise diagnosis in different scenarios using photoacoustic and fluorescence imaging with dual-modality nanoparticles. AB - Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide comprehensive in vivo physiological and pathological information. However, currently there are limited probes available that can realize both fluorescence and photoacoustic imaging, and advanced biomedical applications for applying this dual-modality imaging approach remain underexplored. In this study, we developed a dual modality photoacoustic-fluorescence imaging nanoprobe, ICG-loaded Au@SiO2, which was uniquely designed, consisting of gold nanorod cores and indocyanine green with silica shell spacer layers to overcome fluorophore quenching. This nanoprobe was examined by both PAI and FMI for in vivo imaging on tumor and ischemia mouse models. Our results demonstrated that the nanoparticles can specifically accumulate at the tumor and ischemic areas and be detected by both imaging modalities. Moreover, this dual-modality imaging strategy exhibited superior advantages for a precise diagnosis in different scenarios. The new nanoprobe with the dual-modality imaging approach holds great potential for diagnosis and stage classification of tumor and ischemia related diseases. PMID- 27406827 TI - Villous Adenoma Arising at the Hepaticojejunostomy Site (HJ Site): First Report of an Unusual Case. PMID- 27406826 TI - Mitochondrial beta-Carotene 9',10' Oxygenase Modulates Prostate Cancer Growth via NF-kappaB Inhibition: A Lycopene-Independent Function. AB - : Despite numerous inquiries into protective roles of lycopene in prostate cancer prevention or therapy, little is known about mechanisms by which lycopene or its metabolites inhibit prostate cancer. The enzyme beta-carotene 9',10'-oxygenase (BCO2), which catalyzes asymmetric cleavage of several carotenoids, is the principal regulator of lycopene metabolism, but the range of BCO2 biological functions is incompletely understood. This study investigated expression and functional roles of BCO2 in human prostate cancer. Expression of the bco2 gene is dramatically decreased in prostate cancer tissue and in a range of prostate cancer cell lines as compared with nonneoplastic prostate tissue and normal prostatic epithelial cells, respectively. Inhibition of DNA methyltransferase activity restored bco2 expression in prostate cancer cell lines tested. Treatment with lycopene or its metabolite, apo-10-lycopenal, also increased bco2 expression and reduced cell proliferation in androgen-sensitive cell lines, but lycopene neither altered bco2 expression nor cell growth in androgen-resistant cells. Notably, restoring bco2 expression in prostate cancer cells inhibited cell proliferation and colony formation, irrespective of lycopene exposure. Exogenous expression of either wild-type BCO2 or a mutant (enzymatically inactive) BCO2 in prostate cancer cells reduced NF-kappaB activity and decreased NF-kappaB nuclear translocation and DNA binding. Together, these results indicate epigenetic loss of BCO2 expression is associated with prostate cancer progression. Moreover, these findings describe previously unanticipated functions of BCO2 that are independent of its enzymatic role in lycopene metabolism. IMPLICATIONS: This study identifies BCO2 as a tumor suppressor in prostate cancer. BCO2-mediated inhibition of NF-kappaB signaling implies BCO2 status is important in prostate cancer progression. Mol Cancer Res; 14(10); 966-75. (c)2016 AACR. PMID- 27406828 TI - A Cell-Penetrating Peptide Targeting AAC-11 Specifically Induces Cancer Cells Death. AB - AAC-11 is an antiapoptotic protein that is upregulated in most cancer cells. Increased expression of AAC-11 confers a survival advantage when cancer cells are challenged with various stresses and contributes to tumor invasion and metastases, whereas its deregulation reduces resistance to chemotherapeutic drugs. The antiapoptotic effect of AAC-11 may be clinically relevant as its expression correlates with poor prognosis in several human cancers. Thus, inactivation of AAC-11 might constitute an attractive approach for developing cancer therapeutics. We have developed an AAC-11-derived cell-penetrating peptide, herein named RT53, mimicking in part the heptad leucine repeat region of AAC-11, which functions as a protein-protein interaction module, and that can prevent AAC-11 antiapoptotic properties. In this study, we investigated the anticancer effects of RT53. Our results indicate that RT53 selectively kills cancer cells while sparing normal cells. RT53 selectively inserts into the membranes of cancer cells, where it adopts a punctate distribution and induces membranolysis and release of danger-associated molecular pattern molecules. Systemic administration of RT53 inhibited the growth of preexisting BRAF wild type and V600E mutant melanoma xenograft tumors through induction of apoptosis and necrosis. Toxicological studies revealed that repetitive injections of RT53 did not produce significant toxicity. Finally, RT53-killed B16F10 cells induced tumor growth inhibition in immunocompetent mice following a rechallenge with live cancer cells of the same type. Collectively, our data demonstrate that RT53 possesses tumor-inhibitory activity with no toxicity in mice, suggesting its potential as a therapeutic agent for the treatment of melanoma and probably other cancers. Cancer Res; 76(18); 5479-90. (c)2016 AACR. PMID- 27406829 TI - Identification of a Natural Killer Cell Receptor Allele That Prolongs Survival of Cytomegalovirus-Positive Glioblastoma Patients. AB - By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells in impacting disease progression in this setting. We characterized 108 glioblastoma patients and 454 healthy controls for HLA-A,-B,-C, NK-cell KIR receptors, and CMV-specific antibodies and correlated these metrics with clinical parameters. Exome sequences from a large validation set of glioblastoma patients and control individuals were examined from in silico databases. We demonstrated that the KIR allele KIR2DS4*00101 was independently prognostic of prolonged survival. KIR2DS4*00101 displayed 100% concordance with cognate HLA-C1 ligands in glioblastoma patients, but not controls. In the context of both HLA-C1/C2 ligands for the KIR2DS4 receptor, patient survival was further extended. Notably, all patients carrying KIR2DS4*00101 alleles were CMV seropositive, but not control individuals, and exhibited increased NK-cell subpopulations, which expressed the cytotoxicity receptors CD16, NKG2D, and CD94/NKG2C. Finally, healthy controls exhibited a reduced risk for developing glioblastoma if they carried two KIR2DS4*00101 alleles, where protection was greatest among Caucasian individuals. Our findings suggest that KIR2DS4*00101 may offer a molecular biomarker to identify intrinsically milder forms of glioblastoma. Cancer Res; 76(18); 5326-36. (c)2016 AACR. PMID- 27406830 TI - The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis. AB - KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. Cancer Res; 76(18); 5383-94. (c)2016 AACR. PMID- 27406831 TI - Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging. AB - Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit. PMID- 27406832 TI - Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound. AB - Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic. PMID- 27406833 TI - External validation of the emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP). AB - OBJECTIVE: The emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP) facilitates low-risk ED chest pain patients early to outpatient investigation. We aimed to validate this rule in a North American population. METHODS: We performed a retrospective validation of the EDACS-ADP using 763 chest pain patients who presented to St Paul's Hospital, Vancouver, Canada, between June 2000 and January 2003. Patients were classified as low risk if they had an EDACS <16, no new ischaemia on ECG and non-elevated serial 0-hour and 2-hour cardiac troponin concentrations. The primary outcome was the number of patients who had a predetermined major adverse cardiac event (MACE) at 30 days after presentation. RESULTS: Of the 763 patients, 317 (41.6%) were classified as low risk by the EDACS-ADP. The sensitivity, specificity, negative predictive value and positive predictive value of the EDACS-ADP for 30-day MACE were 100% (95% CI 94.2% to 100%), 46.4% (95% CI 42.6% to 50.2%), 100% (95% CI 98.5% to 100.0%) and 17.5% (95% CI 14.1% to 21.3%), respectively. CONCLUSIONS: This study validated the EDACS-ADP in a novel context and supports its safe use in a North American population. It confirms that EDACS-ADP can facilitate progression to early outpatient investigation in up to 40% of ED chest pain patients within 2 hours. PMID- 27406834 TI - Discontinuing Tyrosine Kinase Inhibitor Therapy in Chronic Myelogenous Leukemia: Current Understanding and Future Directions. AB - BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically transformed the treatment of patients with chronic myelogenous leukemia (CML). Given the impressive and sustained response to TKI therapy that the majority of treated patients with CML enjoy, recent studies have explored the potential to achieve treatment-free remission in select patients, which may allow these patients to escape the adverse clinical and financial effects associated with life-long TKI therapy. The results of multiple prospective trials have demonstrated that patients who maintain a deep molecular response for at least 2 years with TKI treatment may be eligible for trial of TKI discontinuation. Mounting data indicates that approximately 40% of those who discontinue therapy on trial will remain in remission at least 1 year after TKI discontinuation; the majority of patients with molecular recurrence relapse within the first 6 months after TKI discontinuation, and TKI retreatment is highly effective in restoring response. Sokol score, duration of TKI therapy, depth of molecular response, and the presence of natural killer cells may all be associated with a higher probability of attaining treatment-free remission. Moving forward, emerging data from ongoing TKI discontinuation trials will allow for appropriate selection of patients with CML eligible for this approach, will expand our current understanding of the CML stem cell, and identify therapeutic interventions capable of effectively deleting the malignant hematopoietic stem cell. PMID- 27406836 TI - Description of Trichococcus ilyis sp. nov. by combined physiological and in silico genome hybridization analyses. AB - Species of the genus Trichococcus share high similarity of their 16S rRNA gene sequences (>99 %). Digital DNA-DNA hybridization values (dDDH) among type strains of all described species of the genus Trichococcus (T. flocculiformis DSM 2094T, T. pasteurii DSM 2381T, T. collinsii DSM 14526T, T. palustris DSM 9172T, and T. patagoniensisDSM 18806T) indicated that Trichococcus sp. strain R210T represents a novel species of the genus Trichococcus. The dDDH values showed a low DNA relatedness between strain R210T and all other species of the genus Trichococcus (23-32%). Cells of strain R210T were motile, slightly curved rods, 0.63-1.40*0.48 0.90 um and stained Gram-positive. Growth was optimal at pH 7.8 and at temperature of 30 degrees C. Strain R210T could utilize several carbohydrates, and the main products from glucose fermentation were lactate, acetate, formate and ethanol. The genomic DNA G+C content of strain R210T was 47.9 mol%. Based on morphological, physiological and biochemical characteristics along with measured dDDH values for all species of the genus Trichococcus, it is suggested that strain R210T represents a novel species within the genus Trichococcus, for which the name Trichococcus ilyis sp. nov. is proposed. The type strain is R210T (=DSM 22150T=JCM 31247T). PMID- 27406837 TI - Perioperative cardiology: an inspiring arena for the Chameleon doctor. PMID- 27406838 TI - Sixteen-year nationwide trends in antithrombotic drug use in Denmark and its correlation with landmark studies. AB - OBJECTIVE: Antithrombotic drugs are widely used in the prevention and treatment of cardiovascular diseases; yet, nationwide long-term usage trends remain unexplored. We examined long-term trends in the use of antithrombotic drugs in Denmark. METHODS: Using nationwide prescription data, we obtained information on primary care use of antiplatelet drugs, vitamin K antagonists (VKA), non-vitamin K antagonist oral anticoagulants (NOAC), heparins and fondaparinux during 1999 2014. RESULTS: During the 16-year period, the use of antithrombotic drugs per 1000 inhabitants/day increased from 64 to 96 defined daily doses (DDD), and the prevalence proportion of users doubled from 5.1% to 9.6% of the Danish population. From 1999 to 2014, there was an increased use of both antiplatelet drugs (from 60 to 79 DDD per 1000 inhabitants/day) and VKA (from 4 to 9 DDD per 1000 inhabitants/day). NOAC was marketed in 2008 and had an abrupt rise in use to 8 DDD per 1000 inhabitants/day in 2014. The use of heparins and fondaparinux increased slightly during the study period (from 0 to 0.6 DDD per 1000 inhabitants/day). Hospital use of antithrombotic drugs also increased during the study period, but constituted a minor part of the total use (4 DDD per 1000 inhabitants/day in 2014). CONCLUSIONS: Considerable changes have occurred in the use of antithrombotic drugs during the past 16 years, including the introduction of several new and increasingly used treatment modalities such as NOAC. The trends in use of individual drugs correlate well with the publication of landmark studies. PMID- 27406840 TI - N-(2-Ethylhexyl)carbazole: A New Fluorophore Highly Suitable as a Monomolecular Liquid Scintillator. AB - The synthesis, photophysical properties, and applications in scintillation counting of N-(2-ethylhexyl)carbazole (EHCz) are reported. This molecule displays all of the required characteristics for an efficient liquid scintillator (emission wavelength, scintillation yield), and can be used without any extra fluorophores. Thus, its scintillation properties are discussed, as well as its fast neutron/gamma discrimination. For the latter application, the material is compared with the traditional liquid scintillator BC-501 A, and other liquid fluorescent molecules classically used as scintillation solvents, such as xylene, pseudocumene (PC), linear alkylbenzenes (LAB), diisopropylnaphthalene (DIN), 1 methylnaphthalene (1-MeNapht), and 4-isopropylbiphenyl (iPrBiph). For the first time, an excimeric form of a molecule has been advantageously used in scintillation counting. A moderate discrimination between fast neutrons and gamma rays was observed in bulk EHCz, with an apparent neutron/gamma discrimination potential half of that of BC-501 A. PMID- 27406839 TI - Cell-matrix mechanics and pattern formation in inflammatory cardiovascular calcification. AB - Calcific diseases of the cardiovascular system, such as atherosclerotic calcification and calcific aortic valve disease, are widespread and clinically significant, causing substantial morbidity and mortality. Vascular cells, like bone cells, interact with their matrix substrate through molecular signals, and through biomechanical signals, such as traction forces transmitted from cytoskeleton to matrix. The interaction of contractile vascular cells with their matrix may be one of the most important factors controlling pathological mineralisation of the artery wall and cardiac valves. In many respects, the matricrine and matrix mechanical changes in calcific vasculopathy and valvulopathy resemble those occurring in embryonic bone development and normal bone mineralisation. The matrix proteins provide a microenvironment for propagation of crystal growth and provide mechanical cues to the cells that direct differentiation. Small contractions of the cytoskeleton may tug on integrin links to sites on matrix proteins, and thereby sense the stiffness, possibly through deformation of binding proteins causing release of differentiation factors such as products of the members of the transforming growth factor-beta superfamily. Inflammation and matrix characteristics are intertwined: inflammation alters the matrix such as through matrix metalloproteinases, while matrix mechanical properties affect cellular sensitivity to inflammatory cytokines. The adhesive properties of the matrix also regulate self-organisation of vascular cells into patterns through reaction diffusion phenomena and left-right chirality. In this review, we summarise the roles of extracellular matrix proteins and biomechanics in the development of inflammatory cardiovascular calcification. PMID- 27406841 TI - Impaired CD23 and CD62L expression and tissue inhibitors of metalloproteinases secretion by eosinophils in adults with atopic dermatitis. AB - BACKGROUND: Eosinophils are multifunctional, polymorphonuclear leucocytes that secrete proteins within cytoplasmic granules, such as cytokines, chemokines, metalloproteinases (MMPs) and metalloproteinases tissue inhibitors (TIMPs). Although eosinophilia is a hallmark of atopic dermatitis (AD), several functional aspects of eosinophils remain unknown. OBJECTIVE: We aimed to evaluate the phenotype and functional response of eosinophils under staphylococcal enterotoxin B (SEB) and Toll-like receptor (TLR)-2/6 (FSL-1) stimulation in the secretion of CCL5, MMPs and TIMPs in adults with AD. METHODS: Forty-one adult patients with AD and 45 healthy controls enrolled for the study. Phenotype of eosinophils from granulocytes of peripheral blood was analysed by flow cytometry. We performed evaluation of CCL5 (cytometric bead array), MMP and TIMP (ELISA) secretion, in culture supernatants of purified eosinophils stimulated with SEB or TLR2/6 agonist (FSL-1). RESULTS: We found a higher frequency of LIN1- CCR3+ eosinophils, and decreased expression of CD23 and CD62L receptors in eosinophils of AD patients. There was no difference in MMP and TIMP serum levels between the evaluated groups. However, we detected decreased basal levels of TIMP-1, TIMP-2 and CCL5 in culture supernatants from purified, unstimulated eosinophils from AD patients. CONCLUSION: In adults with AD, phenotypical features of eosinophils reveal decreased expression of early activation and L-selectin receptors. Regarding the functional profile of purified eosinophils related to tissue remodelling in atopic dermatitis, innate immune stimulation (TLR2/6 agonist and SEB) did not affect the ratio of MMP/TIMPs secretion in AD. Our findings reinforce the potential breakdown in tissue remodelling process mediated by eosinophils in AD. PMID- 27406842 TI - Predictors and Prognostic Impact of Progressive Ischemic Mitral Regurgitation in Patients With Advanced Ischemic Cardiomyopathy: A Multimodality Study. AB - BACKGROUND: Ischemic mitral regurgitation (IMR) is associated with poor outcomes. It is unknown what factors contribute to progression of IMR and how progressive IMR affects outcomes. We sought to determine imaging predictors of IMR progression and to determine if progressive IMR is an independent predictor of survival in patients with advanced ischemic cardiomyopathy. METHODS AND RESULTS: Consecutive advanced ischemic cardiomyopathy patients who underwent cardiac magnetic resonance and echocardiograms at baseline with echocardiographic follow up were studied. Cardiac magnetic resonance was used to assess left ventricular volumes, infarct size, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. Repeated measures mixed effects and Cox proportional hazards regression models were built to identify predictors of IMR progression and survival. We evaluated 336 patients (age, 62+/-11 years) over a median follow-up time of 54 months: 154 patients were subsequently revascularized, and 182 patients were medically treated. Ninety-eight patients (29%) demonstrated an increase in EROA values of >=0.1 cm(2). There were 87 adverse events (death or transplant). On multivariable analysis, infarct size (P<0.001), progression in IMR (P=0.008), age (P=0.003), and baseline EROA (P=0.010) were independently associated with adverse events. Independent predictors of IMR progression were as follows: baseline EROA (P<0.001), left ventricular end-systolic volume index (P=0.014), and total scar (P=0.036). CONCLUSIONS: IMR frequently increases in severity, and progression is independently associated with adverse left ventricular remodeling and infarct size, as assessed by cardiac magnetic resonance. Furthermore, IMR progression is a powerful independent predictor of adverse events, even after controlling for the severity of IMR at baseline. PMID- 27406843 TI - Predictors of Long-Term Outcomes in Asymptomatic Patients With Severe Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Exercise Echocardiography. AB - BACKGROUND: In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess incremental prognostic utility of exercise stress echocardiography. METHODS AND RESULTS: We studied 533 such patients (age, 66+/-13 years; 78% men; 31% with coronary artery disease) who underwent exercise stress echocardiography between 2001 and 2012. Clinical, echocardiographic, and exercise variables (metabolic equivalents [METs], % of age sex-predicted METs and heart rate recovery at first minute post exercise) were recorded. The end point was all-cause mortality. The Society of Thoracic Surgeons score, left ventricular ejection fraction, mean resting aortic valve (AV) gradient, indexed AV area, METs, and heart rate recovery were 2.9+/-3%, 58+/-4%, 35+/-11 mm Hg, 0.47+/-0.1 cm(2)/m(2), 7.8+/-3, and 26+/-12 bpm, respectively. Only 50% achieved >100%, whereas 26% achieved <85% age-sex-predicted METs. There were no major exercise stress echocardiography-related complications. Over 6.9+/ 3 years, 341 (64%) underwent AV replacement (54% isolated), and there were 104 (20%) deaths. On multivariable Cox proportional hazard survival analysis, a higher Society of Thoracic Surgeons score (hazard ratio, 1.21), lower % age-sex predicted METs (hazard ratio 1.15), and slower heart rate recovery (hazard ratio, 1.22) were associated with higher longer-term mortality, whereas AV replacement (time-dependent covariate, hazard ratio, 0.26) was associated with improved survival. The addition of % age-sex-predicted METs to the Society of Thoracic Surgeons score resulted in significant reclassification of longer-term mortality risk (integrated discrimination index, 0.07 [0.03-0.11; P<0.001). CONCLUSIONS: In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing exercise stress echocardiography, a lower % of age sex-predicted METs and slower heart rate recovery were associated with longer term mortality, whereas AV replacement was associated with improved survival. PMID- 27406844 TI - Dramatic Response to Tocilizumab Before Emergency Surgery in Severe Active Takayasu Disease. PMID- 27406845 TI - Anticipating the Vicious Circle of Postinfarction Mitral Regurgitation: Imaging Insights. PMID- 27406846 TI - Asymptomatic Patients With Severe Aortic Stenosis Are Not All Created Equal: A Role for Stress Performance and Heart Rate Recovery During Stress Echocardiography? PMID- 27406847 TI - GENDER INFLUENCES DIFFERENTIATION OF CHITIN AMONG BODY PARTS. AB - Earlier reports have established that chitin isolates from each body part of an insect cuticle can exhibit diverse physicochemical properties. But it is still unknown if the gender of the insect can influence characteristics of chitin isolates from different body parts. The present study addresses this question. As a result, important physicochemical differences in the chitin samples from different body parts of Melolontha sp. were recorded on the basis of sex. The chitin samples were extracted from eight different body parts (antennae, head, eyes, thorax, abdomen, elytra, hindwings, and legs) of female and male. The most remarkable variations in the chitin isolates from female and male body parts were recorded in chitin content, crystallinity, thermal stability, and surface morphology. And also it was wondered these chitin isolates from different body parts of female and male could find different applications. To check this hypothesis, the chitin samples from female and male were interacted with bovine serum albumin (BSA) protein and important variations were observed. PMID- 27406848 TI - Metabolic engineering of Cyanobacteria and microalgae for enhanced production of biofuels and high-value products. AB - A lot of research has been performed on Cyanobacteria and microalgae with the aim to produce numerous biotechnological products. However, native strains have a few shortcomings, like limitations in cultivation, harvesting and product extraction, which prevents reaching optimal production value at lowest costs. Such limitations require the intervention of genetic engineering to produce strains with superior properties. Promising advancements in the cultivation of Cyanobacteria and microalgae have been achieved by improving photosynthetic efficiency through increasing RuBisCO activity and truncation of light-harvesting antennae. Genetic engineering has also contributed to final product extraction by inducing autolysis and product secretory systems, to enable direct product recovery without going through costly extraction steps. In this review, we summarize the different enzymes and pathways that have been targeted thus far for improving cultivation aspects, harvesting and product extraction in Cyanobacteria and microalgae. With synthetic biology advancements, genetically engineered strains can be generated to resolve demanding process issues and achieve economic practicality. This comprehensive overview of gene modifications will be useful to researchers in the field to employ on their strains to increase their yields and improve the economic feasibility of the production process. PMID- 27406850 TI - Addressing Physical Health Needs of Individuals With Schizophrenia Using Orem's Theory. AB - People with schizophrenia have increased morbidity and mortality rates associated with poor physical health that requires a holistic and comprehensive nursing approach. Dorothy Orem's self-care deficit nursing theory (SCDNT) has made a substantive contribution to nursing by focusing on people as whole entities who engage with their environment to sustain health. We offer an expanded view of the SCDNT by showing how it is a useful framework for nurses to integrate interpretive, empirical, and critical theoretical perspectives for addressing both the physical and mental health needs for people with schizophrenia. Understanding patient needs through different theoretical lenses will help nurses integrate high-quality, evidence-based care with patients' realities, needs, and values while considering the influence of the broader sociopolitical context. We demonstrate how the SCDNT allows nurses incorporate a critical perspective for critiquing the influence of societal barriers on individual's health and advocate for initiatives to address the complex sociopolitical, economic, and contextual factors that affect the physical well-being of individuals with schizophrenia. PMID- 27406849 TI - Keratosis punctata of the palmar creases in a 68-year-old African-American man. PMID- 27406851 TI - Tepidibacillus decaturensis sp. nov., a microaerophilic, moderately thermophilic iron-reducing bacterium isolated from 1.7 km depth groundwater. AB - A Gram-stain-negative, microaerophilic rod-shaped organism designated as strain Z9T was isolated from groundwater of 1.7 km depth from the Mt. Simon Sandstone of the Illinois Basin, Illinois, USA. Cells of strain Z9T were rod shaped with dimensions of 0.3*(1-10) um and stained Gram-negative. Strain Z9T grew within the temperature range 20-60 degrees C (optimum at 30-40 degrees C), between pH 5 and 8 (optimum 5.2-5.8) and under salt concentrations of 1-5 % (w/v) NaCl (optimum 2.5 % NaCl). In addition to growth by fermentation and nitrate reduction, this strain was able to reduce Fe(III), Mn(IV), Co(III) and Cr(VI) when H2 or organic carbon was available as the electron donor, but did not actively reduce oxidized sulfur compounds (e.g. sulfate, thiosulfate or S0). The G+C content of the DNA from strain Z9T was 36.1 mol%. Phylogenetic analysis of the 16S rRNA gene from strain Z9T showed that it belongs to the class Bacilli and shares 97 % sequence similarity with the only currently characterized member of the genus Tepidibacillus, T.fermentans. Based on the physiological distinctness and phylogenetic information, strain Z9T represents a novel species within the genus Tepidibacillus, for which the name Tepidibacillus decaturensis sp. nov. is proposed. The type strain is Z9T (=ATCC BAA-2644T=DSM 103037T). PMID- 27406852 TI - Influence of acylpeptide hydrolase polymorphisms on valproic acid level in Chinese epilepsy patients. AB - BACKGROUND: Concomitant use of meropenem (MEPM) can dramatically decrease valproic acid (VPA) plasma level. It is accepted that inhibition in acylpeptide hydrolase (APEH) activity by MEPM coadministration was the trigger of this drug drug interaction. AIM: To investigate the influence of APEH genetic polymorphisms on VPA plasma concentration in Chinese epilepsy patients. PATIENTS & METHODS: Urinary VPA-d6 beta-D-glucuronide concentration was determined in 19 patients with VPA treatment alone (n = 10) or concomitant use with MEPM (n = 9). A retrospective study was performed on 149 epilepsy patients to investigate the influence of APEH polymorphisms rs3816877 and rs1131095 on adjusted plasma VPA concentration (CVPA) at steady-state. RESULTS: Urinary VPA-d6 beta-D-glucuronide (VPA-G) concentration was increased significantly in patients with MEPM coadministration. The CVPA of patients carrying the APEH rs3816877 C/C genotype was significantly higher than that of C/T carriers, and the difference was still obvious when stratified by UGT2B7 rs7668258 polymorphism. CONCLUSION: APEH polymorphism has significant influence on VPA pharmacokinetics in Chinese population. PMID- 27406853 TI - Interleukin 31 is involved in intrahepatic cholestasis of pregnancy. AB - Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder characterized by maternal itching and altered liver function. Interleukin (IL)-31 is known to be involved in the pathogenesis of pruritic inflammatory skin diseases. In a three year period, 13 women with a singleton pregnancy and a diagnosis of intrahepatic cholestasis (ICP) were enrolled together with 26 healthy single pregnant women who concluded an uncomplicated pregnancy. The inclusion criteria were itching and elevated levels of liver transaminases. Median serum levels of IL-31 were significantly higher in ICP patients than in the control group (p = 0.004). Furthermore, IL-31 values were directly dependent on liver transaminase levels. PMID- 27406854 TI - Differential Diagnosis in Pediatrics: A Probabilistic Approach. PMID- 27406856 TI - Electrochemically Tunable Resistance of Nanoporous Platinum Produced by Dealloying. AB - The extremely high surface-to-volume ratio of nanoporous platinum (np-Pt) produced by dealloying was applied for tuning electrical resistance by surface charging. In the as-dealloyed state, a characteristic sign-inversion of the charging-induced resistance variation occurs, which can be associated with the electronic structure of PtO. After electrochemical reduction, the relative resistance variations of np-Pt of up to 58% could be generated by electrochemically induced adsorption and desorption, which was 1 order of magnitude larger compared with that of cluster-assembled nanocrystalline Pt. Although the maximum resistance variation was also higher than that of dealloyed nanoporous gold (np-Au), the resistance variation related to the imposed charge was reduced owing to the higher bulk resistance of Pt compared with that of Au. The sign-inversion behavior of the resistance could be recovered by re-oxidation. PMID- 27406857 TI - Electrical impedance spectroscopy of a PET chip sandwiched between two disk electrodes: understanding the contribution of the polymer/electrode interface. AB - This work is devoted to the understanding of the dielectric impedance response of a semi-crystalline polyethylene terephthalate (PET) membrane sandwiched between two disk electrodes under alternate voltage excitation in the frequency range between 1 MHz and 25 mHz. Experimental results obtained for various PET thicknesses (36, 50 and 100 MUm) highlighted the influence of the contact resistance at the electrode/polymer interface. For a better understanding of the PET/electrode interface behaviour, the experiments were compared with simulations performed for three different descriptions: the direct use of electrical equivalent circuits, an analytical model accounting for a power-law distribution of resistivity, and a numerical model (finite element simulations of the whole cell). The results highlight that the resistivity distribution obtained using the power-law model provided an appropriate description of the system in the frequency range investigated while the use of the CPE model is only consistent for low-frequencies (below 1 Hz). PMID- 27406855 TI - Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model. AB - Compelling evidence has indicated that dysregulated glucose metabolism links Alzheimer's disease (AD) and diabetes mellitus (DM) via glucose metabolic products. Nevertheless, because of the lack of appropriate animal models, whether chronic hyperglycemia worsens AD pathologies in vivo remains to be confirmed. Here, we crossed diabetic mice (Pdx1(+/-) mice) with Alzheimer mice (APP/PS1 transgenic mice) to generate Pdx1(+/-)/APP/PS1. We identified robust increases in tau phosphorylation, the loss of the synaptic spine protein, amyloid-beta (Abeta) deposition and plaque formation associated with increased microglial and astrocyte activation proliferation, which lead to exacerbated memory and cognition deficits. More importantly, we also observed increased glucose intolerance accompanied by Pdx1 reduction, the formation of advanced glycation end-products (AGEs), and the activation of the receptor for AGEs (RAGE) signaling pathways during AD progression; these changes are thought to contribute to the processing of Abeta precursor proteins and result in increased Abeta generation and decreased Abeta degradation. Protein glycation, increased oxidative stress and inflammation via hyperglycemia are the primary mechanisms involved in the pathophysiology of AD. These results indicate the pathological relationship between these diseases and provide novel insights suggesting that glycemic control may be beneficial for decreasing the incidence of AD in diabetic patients and delaying AD progression. PMID- 27406858 TI - Dietary habits and neurological features of Parkinson's disease patients: Implications for practice. AB - BACKGROUND & AIMS: Parkinson's disease (PD) patients can benefit considerably from appropriate nutritional care, particularly from diet. However, there is limited evidence on the eating habits of PD patients and their relationship with the features of the disease. METHODS: We conducted a large case-control study. Consecutive PD patients (N = 600) receiving systematic nutritional care and healthy controls (N = 600) matched (1:1) for age, gender, education, physical activity level and residence were studied using a 66-item food frequency questionnaire. The relationship between dietary habits and the following features of PD were investigated in patients: body weight, energy balance, constipation, and levodopa therapy (dose) and its related motor complications. RESULTS: PD patients had lower BMI and reported higher food intake than controls. BMI was found to be inversely associated with disease duration and severity, and levodopa related motor complications, whereas energy intake was positively associated with these variables. An increase in protein intake by 10 g over physiological requirements (0.8 g/kg/day) corresponded to a mean increase in levodopa dose of 0.7 mg/kg/day. Constipation was also associated with higher levodopa requirements. Finally, protein intake and its distribution throughout the day influenced levodopa-related motor complications. CONCLUSION: The management of protein intake and the treatment of constipation should be considered to be an integral part of the care of PD patients. Attention should always be focused on energy intake also. This would result in the maintenance of nutritional status, the optimization of levodopa-therapy and the minimization of its related motor complications. PMID- 27406860 TI - Interaction of chlorhexidine with trisEDTA or miconazole in vitro against canine meticillin-resistant and -susceptible Staphylococcus pseudintermedius isolates from two UK regions. AB - BACKGROUND: Topical therapy is an important alternative to systemic antibacterial therapy for treatment of canine superficial pyoderma in light of the emergence of multidrug-resistant staphylococci. Chlorhexidine is widely used in shampoo products alone or in combination with miconazole or tromethamine ethylenediaminetetraacetic acid (trisEDTA). Comparisons of these combinations have not been made. HYPOTHESIS/OBJECTIVES: To determine minimum inhibitory concentrations (MICs) of combinations of chlorhexidine/miconazole and chlorhexidine/trisEDTA in vitro in a collection of Staphylococcus pseudintermedius (SP) from northern (NUK) and southeastern (SEUK) United Kingdom (UK) sources. METHODS: MICs of chlorhexidine, miconazole, trisEDTA and combinations of chlorhexidine/miconazole (1:1) or chlorhexidine/trisEDTA (80:16:1 and 80:5:1) were determined for 196 canine SP isolates from NUK [49 meticillin resistant (MRSP), 50 meticillin-susceptible (MSSP)] and fom SEUK (48 MRSP, 49 MSSP) using agar dilution. RESULTS: TrisEDTA alone did not inhibit growth. Chlorhexidine/miconazole MICs (median = 0.5 mg/L) were lower than those of either drug alone (P < 0.05) and lower than chlorhexidine/trisEDTA MICs (median = 1 mg/L; P < 0.0005) in each bacterial type and from both regions, except for miconazole in NUK MSSP. An additive interaction was noted between chlorhexidine and miconazole or trisEDTA (80:16:1 ratio) in 79 and 43 isolates, respectively, whereas antagonism between chlorhexidine and trisEDTA was noted for three isolates. NUK isolates were more susceptible than SEUK isolates (P < 0.05), except MRSP exposed to chlorhexidine and the chlorhexidine/trisEDTA (80:16:1) combination. CONCLUSIONS AND CLINICAL IMPORTANCE: These low MICs are likely to be exceeded by topical therapy. Evaluation of the mechanisms by which chlorhexidine combinations interact to reduce MICs is warranted, in view of increasing concerns of biocide tolerance in staphylococci. PMID- 27406859 TI - Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA. AB - BACKGROUND & AIMS: The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. METHODS: Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. RESULTS: The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009). CONCLUSIONS: Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids. PMID- 27406861 TI - Management of Aplasia. AB - Prior to the availability of specific treatment for aplastic anaemia (AA) with antithymocyte globulin (ATG) and cyclosporin or bone marrow transplantation (BMT), most patients died within 6 months of presentation, but the survival of patients with severe AA has improved dramatically over the last two decades and many patients now survive long term. Nevertheless, AA still remains a potentially life threatening disease. Because response to treatment with ATG and cyclosporin is delayed for two to three months and sometimes longer, patients usually need intensive transfusional support and careful attention to infection prophylaxis and treatment, particularly fungal infection. It is important to adopt a careful transfusional policy at diagnosis, in particular to help prevent HLA alloimmunisation which results in refractoriness to platelet transfusions, and sensitisation to minor histocompatibility antigens which is thought to mediate graft rejection between HLA identical siblings. The indications for immunosuppressive therapy or HLA identical sibling BMT are fairly clear, but transplantation from volunteer unrelated donors remains a highly controversial and high risk procedure in patients with AA. The effects of haemopoietic growth factors in AA patients have been perhaps not surprisingly disappointing, and not without significant toxicity, with the exception of granulocyte colony stimulating factor (G-CSF) which is well tolerated clinically. G-CSF may be useful in the treatment of severe resistant infections and it may be of benefit when used after treatment with ATG and cyclosporin. PMID- 27406862 TI - Understanding the Graft-Versus-Leukaemia Reaction. AB - The role of the immune response in control and erradication of leukaemia remains controversial but there is increasing evidence that the principal mechanism of cure after intensive chemotherapy and allogeneic BMT is immune mediated. This is evidenced by the observations of a reduced risk of leukaemia relapse after allogeneic BMT when compared with autologous or syngeneic BMT. Furthermore, an increased incidence of leukaemic relapse has been reported after aggressive GvHD prophylaxis with cyclosporin or lymphocyte depletion. The association between GvHD and the graft-versus-leukaemia activity of allogeneic BMT is strong and has led to a number of workers concluding that GvL might be inseparable from GvHD although there is increasing evidence that this is not so. The lymphocyte subsets responsible for GvHD and GvL remain to be elucidated in man despite intensive efforts. Certainly T cells, natural killer cells and a population of in vivo activated killer cells are involved in GvL and an effective immune response probably requires a combined approach. The target antigens of GvL are also controversial. The majority of GvL studies have been conducted in the allogeneic transplant setting in which activity to leukaemia-specific peptides is easily masked by reactivity to undetected MHC mismatches and to minor histocompatibility antigens. Despite this the search for leukaemia-specific peptides has been fruitful in the case of the product of the BCR/ABL translocation in CML. The ultimate aim of a number of groups in all aspects of oncology is the development of effective and specific immunotherapy. A variety of approaches have been attempted over the last 80 years, including vaccination with irradiated leukaemic blasts and numerous trials of interleukin-2. We now know more about the mechanisms of induction of immunity than ever before and this knowledge, combined with sophisticated molecular biology and virology, promises to revolutionise the immunotherapy of leukaemia over the next ten years. PMID- 27406864 TI - Late Relapse After Allogeneic Bone Marrow Transplant In a Patient With Myelodysplasia. AB - Bone Marrow Transplantation remains the only potentially curative procedure for patients with Myelodysplastic syndrome (MDS). Patients who remain disease free 5 years after transplantation have usually been considered cured, but more recent experience challenges this expectation. We report here a case of MDS who relapsed more than 5 years following transplant, and was then successfully treated with a second transplant. PMID- 27406863 TI - Fluorescence In Situ Hybridization: Trisomy 12 Follow-up In Hairy Cell Leukemia. AB - Peripheral white blood cells from five patients with hairy cell leukemia (HCL) were studied applying fluorescence in situ hybridization (FISH) using heparinized peripheral blood, biotin-labeled chromosome 12-specific alpha satellite DNA probe and biotin fluorescein-labeled avidin to detect hybridization. This methodology is ideal to investigate the incidence of numerical chromosomal abnormalities of both interphase and metaphase cells. Blood samples from 28 normal subjects were included as control samples. Trisomy 12 was considered to be present when >=4% of cells had three hybridization spots. Trisomy 12 was detected in three of the five patients at different stages of their evolution. Trisomy 12 was also evident in two patients upon relapse of the HCL. When treatment with interferon alfa (IFN) and steroids was started, clinical and analytical remission were achieved and trisomy 12 disappeared. In one patient trisomy 12 persisted regardless of treatment with IFN and a good clinical evolution. Our results show that trisomy 12 was detected in HCL with FISH at a higher frequency than that previously reported by cytogenetic analysis in either peripheral blood or in cultivated cell lines. These results indicate that the presence of trisomy 12 may be a useful marker for the presence of HCL cells, to check the percentage of trisomic cells and that trisomy 12 is also a useful marker to indicate the activity of the disease. PMID- 27406865 TI - Microangiopathic Hemolytic Anemia Associated with the use of both Cyclosporin A and FK506 (Tacrolimus) in the Same Patient. AB - Microangiopathic hemolytic anemia (MAHA) is a well recognized complication of cyclosporin A (CyA) immunosupressive therapy post bone marrow and solid organ transplant but has rarely been reported in association with FK506 (tacrolimus), we describe a unique patient in whom both CyA and FK506 appear to have caused microangiopathy following an allogeneic peripheral stem cell transplant. PMID- 27406866 TI - G-CSF Regulates the Expression of mRNA for Collagen Type VI and Collagen VI Production in Human Bone Marrow Stromal Cells. AB - Bone marrow stromal cells produce several extracellular matrix molecules, which are instrumental for progenitor cell attachement, development and survival. Evidence available suggests that collagen type VI produced by marrow stroma, plays a role in progenitor cell attachment and matrix conformation. To investigate whether the steady-state level of collagen VI expression is modulated by growth factors, we analyzed the effect of G-CSF in the expression of collagen type VI mRNA and collagen VI production by human bone marrow stromal cells. Results show that G-CSF, a growth factor extensively used for the mobilization of progenitor cells, decreases the level of expression of collagen type VI mRNA, but not that of mRNA for collagen type I and fibronectin. The downregulation of collagen VI gene expression was paralleled by a decrease in the secretion and accumulation of collagen VI. Since, G-CSF does not influence the growth of stromal cells, the observed effects are not secondary to proliferative stimulation by growth factor. These results suggest that, in addition to the well established action of G-CSF on progenitor and mature cells, it also modulates via stromal cells, the expresion of a particular type of extracellular matrix component. PMID- 27406867 TI - Thrombocytosis in Malignancy: A Paraneoplastic Syndrome? AB - An increased platelet number may be secondary to many conditions. Malignancies are known to induce thrombocytosis in some cases. We report data of paraneoplastic thrombocytosis recognized in 54 out of 159 patient (33.9%) with reactive thrombocytosis diagnosed in our department over the last 10 years. In most of our patients increased platelet count was observed at the time of diagnosis (33.7%) or during the first year thereafter (35.2%). Evidence of other causes for reactive thrombocytosis including iron deficiency, anemia, inflammatory diseases, surgical procedures including splenectomy, and drugs were observed in 74% of our patients. 35% of our subjects had non fatal hemorrhagic or thrombotic accidents. In about one half of our patients, increased levels of fibrinogen, ESR and plasma alpha2 globulins were observed while 5 hydroxytryptamine (5HT) intraplatelet level was normal in about all these patients. The diagnosis of paraneoplastic thrombocytosis must be postulated only after exclusion of all other reactive conditions. Often an increased platelet count in patients with cancer may be considered a reactive phenomenon. PMID- 27406868 TI - The Release of Tissue Factor Pathway Inhibitor and Platelet Factor 4 After Heparin Injection in Patients with Thrombocytosis. AB - Platelet factor 4 (PF4) and tissue factor pathway inhibitor (TFPI) are two proteins with high affinity for heparin. They are each stored in platelets, as well as on endothelial cell surfaces, from where both are displaced or released following an injection of heparin with a rapid and marked increase in serum levels. Prior work has demonstrated that the platelet count is one of the factors affecting the levels of heparin-releasable PF4. We therefore characterized the response to a dose of intravenous heparin previously demonstrated to completely displace PF4 from the non-platelet pool in subjects with normal or increased platelet counts. Seventeen patients with essential thrombocytosis (ET), 10 patients with polycythemia vera and high platelet counts (PV-H), 7 patients with polycythemia vera and normal platelet counts (PV-N) and 10 controls received an initial bolus of 40 I.U./kg of unfractionated heparin, followed 2 hours later by a 2nd bolus of a fixed dose of 1000 I.U. TFPI activity did not show any variation among the different groups, either before (TFPI) or after (HR-TFPI) the first bolus of heparin: ET, TFPI 92.6 +/- 21.5%, HR-TFPI 298.3 +/- 165.8; PV-H, TFPI 91.5 +/- 32.0, HR-TFPI 210 +/- 1.0; PV-N, TFPI 69.4 +/- 24.0, HR-TFPI 203.0 +/- 79.0; C, TFPI 109.5 +/- 33.5, HR-TFPI 234.0 +/- 60.4. TFPI activity returned to basal values prior to the 2nd injection of heparin, which again elicited a rise in TFPI, albeit smaller due to the lower level of heparin injected. In contrast to the lack of any difference between groups with respect to TFPI, the level of heparin-releasable PF4 (HR-PF4) was significantly higher in ET and PV-H patients compared to PV-N patients or controls. However when normalized for platelet count, both PV-H and PV-N had HR-PF4 levels after the 1st heparin injection that were significantly higher than observed in ET patients (PV-H 1.163 + 0.108, PV-N 1.411 + 0.019, ET 0.737 + 0.086 ng/10/3 platelets) supporting an increased platelet activation in PV. Thus, although platelets contain approximately 5-10% of the total amount of TFPI in plasma, they do not affect the major intravascular pool of TFPI mobilizable by heparin. However, since the concentration at the site of vessel wall injury is enhanced several-fold, TFPI could play a role in competing with PF4 to limit thrombus formation in patients with high platelet count. PMID- 27406869 TI - Mean Platelet Volume in Thrombocytopenic, Preterm Infants. AB - We evaluated the use of mean platelet volume (MPV) as a reliable indicator of bacteremia in neonates. We first established normal MPV values in very low birth weight neonates (< 1 kg and >= 1 kg < 1.8 kg, respectively) in the first 47 days of life. We conclude that MPV is not a reliable predictor of sepsis. However, one subset of thrombocytopenic neonates, with birth weights >= 1 kg < 1.8 kg was identified with significantly increased MPV (P < 0.05) compared to the age matched control. In this group, the thrombocytopenia was not associated with sepsis, and the etiology of the decreased platelet count remained to be determined. PMID- 27406870 TI - Principles of the Polymerase Chain Reaction in Haematology. AB - The polymerase chain reaction (PCR) is an automated process that specifically amplifies selected DNA sequences that are usually chosen to reflect the presence of genes, or parts of genes, in the sample material. Since many genetic alterations resulting in the onset of disease are now detectable using PCR, it can be used as both a diagnostic and prognostic tool. Genetic changes can occur in DNA due to mutation, deletion, inversion or chromosomal translocation. As a consequence, genes become either non functional or are aberrantly expressed. Research in recent years has now associated many defined genetic abnormalities with specific diseases. Therefore detection and surveillance of such lesions has led to disease diagnosis and subsequent monitoring of disease progression, for example, during and after administration of therapeutic regimens. The major effect of PCR in this area is that genetically abnormal cells can be detected within a normal cell population at a far lower incidence level than any other existing technology. Moreover, PCR can be used to identify naturally existing genetic polymorphisms that can be used as personal identifiers, or tags, for a given individual. Where these polymorphisms occur within a genetically modified region resulting in disease, identification of the polymorphism within families can be used as a predictor of disease carrier status or likelihood of inheritance of the disease. PMID- 27406871 TI - Reversal of Life-Threatening Vascular Occlusion by Apheresis in Fulminating Plasmodium Falciparum Malaria. AB - Plasmodium falciparum parasitisation can result in a systemic inflammatory response characterised by profound neurologic complications, renal failure, adult respiratory distress syndrome and disseminated intravascular coagulation with high morbidity and mortality. Complete obstruction to medium sized arteries seems not to have been reported before while the role of sequential whole blood and plasma exchange may be an under-utilised intervention that is life-saving in selected cases. A 25 year old patient was referred with mental confusion, rapidly deteriorating vision, hypotensive and oliguric, massive generalised oedema compressing muscles leading to rhabdomyolysis and impending gangrene of both lower limbs. 1,555 mL of whole blood was exchanged in the cell separator to reverse the haemoglobin of 35g/L, remove parasitised and effete red cells while simultaneously correcting hypovolaemia. Thereafter 4,000mL of fresh frozen plasma was similarly exchanged and 3 * 10(11) platelets given to treat the advanced disseminated intravascular coagulation. Anti-malarial therapy was continued with quinine sulphate and doxycycline for the chloroquin-resistant parasites. The tense swelling of the limbs gradually resolved, thereby avoiding fasciotomies, arterial occlusion reversed and microvascular perfusion was re-established with resolution of all symptoms. Tissue loss was eventually limited to fore foot amputation on the left. The patient has been physically and psychologically rehabilitated and discharged after six weeks in hospital. Malaria, when associated with multiple organ failure, is frequently fatal. Where appropriate, complications-due to vascular occlusion-can be promptly reversed with suitable apheresis. This practical approach is relatively inexpensive and should be available in all centres responsible for managing such patients. PMID- 27406872 TI - Breast reconstruction with single-pedicle TRAM flap in breast cancer patients with low midline abdominal scar. AB - Breast reconstruction with transverse rectus abdominis myocutaneous (TRAM) flap is challenging in patients with low midline abdominal scar. In this study, we aimed to investigate the clinical feasibility of immediate breast reconstruction using single-pedicle TRAM (SP-TRAM) flaps in patients with low midline abdominal scar. There were 4 strict selection criteria: 1) presence at least 3 perforators on the pedicle side; 2) perforators with regional average flow velocity of >20 cm/s; 3) upper edge of the abdominal scar at least 4 cm from the umbilicus; and 4) scar age >1 year. Eight breast cancer patients with low midline abdominal scar (scar group) and 20 without (control group) underwent immediate breast reconstruction with SP-TRAM flaps consisting of zone I and III and zone II tissues. Flap complications, donor-site complications, and cosmetic results were compared between the two groups. All flaps survived and both groups presented similar flap and donor site complications, including fat necrosis, seroma, hematoma, infection, delayed wound healing, and abdominal hernia, and patients in both groups had similar aesthetic results (p > 0.05). Thus, the study demonstrated that breast reconstruction using SP-TRAM flap was a safe approach in carefully selected patients with low midline abdominal scar. PMID- 27406874 TI - Evaluating the healthiness of chain-restaurant menu items using crowdsourcing: a new method. AB - OBJECTIVE: To develop a technology-based method for evaluating the nutritional quality of chain-restaurant menus to increase the efficiency and lower the cost of large-scale data analysis of food items. DESIGN: Using a Modified Nutrient Profiling Index (MNPI), we assessed chain-restaurant items from the MenuStat database with a process involving three steps: (i) testing 'extreme' scores; (ii) crowdsourcing to analyse fruit, nut and vegetable (FNV) amounts; and (iii) analysis of the ambiguous items by a registered dietitian. RESULTS: In applying the approach to assess 22 422 foods, only 3566 could not be scored automatically based on MenuStat data and required further evaluation to determine healthiness. Items for which there was low agreement between trusted crowd workers, or where the FNV amount was estimated to be >40 %, were sent to a registered dietitian. Crowdsourcing was able to evaluate 3199, leaving only 367 to be reviewed by the registered dietitian. Overall, 7 % of items were categorized as healthy. The healthiest category was soups (26 % healthy), while desserts were the least healthy (2 % healthy). CONCLUSIONS: An algorithm incorporating crowdsourcing and a dietitian can quickly and efficiently analyse restaurant menus, allowing public health researchers to analyse the healthiness of menu items. PMID- 27406875 TI - Endocrine resistance in hormone-responsive breast cancer: mechanisms and therapeutic strategies. AB - The majority of breast cancers may be considered hormone responsive due to expression of hormone receptors (HR+). Although endocrine therapy is always considered for advanced HR+ breast cancer, the emergence of resistance is inevitable over time and is present from the start in a proportion of patients. In this review, we explore the mechanisms underlying de novo and acquired resistance to endocrine therapy. We comprehensively review newly approved and emerging therapies that have been developed to counteract specific mechanisms of resistance. We discuss the challenges pertinent to this therapeutic arena including the potential relief of negative regulatory feedback inhibition with compensatory pathway activation and the evolution of molecular changes in HR+ breast cancers during treatment. We discuss strategies to address these challenges in order to develop rational therapy approaches for patients with advanced HR+ breast cancer. PMID- 27406873 TI - PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers. AB - The spleen tyrosine kinase (SYK) regulates immune cell activation in response to engagement of a variety of receptors, making it an intriguing target for the treatment of inflammatory and autoimmune disorders as well as certain B-cell malignancies. We have previously reported on the discovery and preclinical characterization of PRT062607, a potent and highly selective inhibitor of SYK that exhibits robust anti-inflammatory activity in a variety of animal models. Here we present data from our first human studies aimed at characterizing the pharmacokinetics (PK), pharmacodynamics (PD), and safety of PRT062607 in healthy volunteers following single and multiple oral administrations. PRT062607 demonstrated a favorable PK profile and the ability to completely inhibit SYK activity in multiple whole-blood assays. The PD half-life in the more sensitive assays was approximately 24 hours and returned to predose levels by 72 hours. Selectivity for SYK was observed at all dose levels tested. Analysis of the PK/PD relationship indicated an IC50 of 324 nM for inhibition of B-cell antigen receptor-mediated B-cell activation and 205 nM for inhibition of FcepsilonRI mediated basophil degranulation. PRT062607 was safe and well tolerated across the entire range of doses. Clinical PK/PD was related to in vivo anti-inflammatory activity of PRT062607 in the rat collagen-induced arthritis model, which predicts that therapeutic concentrations may be safely achieved in humans for the treatment of autoimmune disease. PRT062607 has a desirable PK profile and is capable of safely, potently, and selectively suppressing SYK kinase function in humans following once-daily oral dosing. PMID- 27406877 TI - The analysis of incontinence episodes and other count data in patients with overactive bladder by Poisson and negative binomial regression. PMID- 27406876 TI - Endocrine tumors associated with the vagus nerve. AB - The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors. PMID- 27406878 TI - Effects of rehabilitation treatment of the upper limb in multiple sclerosis patients and predictive value of neurophysiological measures. AB - BACKGROUND: Dysfunctions of the upper limbs occur in the 66% of multiple sclerosis (MS) patients. To date, no data, about the persistence of the effects of a rehabilitation treatment and no prognostic markers of functional improvement, have been established. AIM: The aim of this study was to define clinical data supporting the efficacy of a rehabilitation treatment in MS patients with upper limb impairment and to find prognostic factors for functional improvement. DESIGN: Pre-post comparison prospective study. SETTING: Two tertiary Italian MS centres: Rome and Siena. POPULATION: Twenty-five consecutive MS patients were tested for eligibility. METHODS: We multidimensionally evaluated 25 consecutive patients with MS-related upper limbs impairment through clinical objective, patient-oriented and neurophysiological measures pre and post a16-week rehabilitation treatment on upper limb sensorimotor function. RESULTS: We found a significant improvement in the Nine Hole Peg Test (9-HPT) at either sides, both at an immediate post-training visit (T1) (left: P=0.018, right: P=0.004) and at a 12-week postintervention assessment visit (T2) (left: P=0.033, right: P=0.022). We also found a positive correlation between the 12-week post-training changes in the 9-HPT and the N14-P20 interpeak of the somatosensory evoked potentials, (rho=0.374, P=0.008). CONCLUSIONS: Our study demonstrates that a rehabilitation treatment can lead to an improvement of the upper limb motor performance in MS patients which continues to persist even after 3 months of treatment discontinuation suggesting a possible role of rehabilitation in neuroplasticity changes. Moreover, we found, in the latency of the N14-P20 interpeak, a possible prognostic marker for the effects of a upper limb rehabilitation treatment in MS patients. CLINICAL REHABILITATION IMPACT: The N14-P20 interpeak could be used as a prognostic marker of the effects of rehabilitation of the upper limb. PMID- 27406879 TI - Efficacy of robot-assisted rehabilitation for the functional recovery of the upper limb in post-stroke patients: a randomized controlled study. AB - BACKGROUND: A prompt and effective physical and rehabilitation medicine approach is essential to obtain recovery of an impaired limb to prevent tendon shortening, spasticity and pain. Robot-assisted virtual reality intervention has been shown to be more effective than conventional interventions and achieved greater improvement in upper limb function. AIM: The aim of this study was to evaluate the effectiveness of robotic-assisted motion and activity in addition to PRM for the rehabilitation of the upper limb in post-stroke inpatients. DESIGN: Randomized controlled trial. SETTING: Departments of Physical and Rehabilitation Medicine from three different hospitals (Sarnico, Brescia; Bergamo; Milan). POPULATION: A total of 54 patients and enrolled 23 men and 31 women with post stroke hemiparesis, aged 18 to 80 years old, enrolled from July 2014 to February 2015. METHODS: Of the 54 enrolled patients, 57% were female (mean age 71+/-12 years), and all had upper limb function deficit post-stroke. The experimental group received a passive mobilization of the upper limb through the robotic device ARMEO Spring and the control group received PRM for 6 consecutive weeks (5 days/week) in addition to traditional PRM. We assessed the impact on functional recovery (Functional Independence Measure [FIM] scale), strength (Motricity Index [MI]), spasticity (Modified Ashworth Scale [MAS]) and pain (Numeric Rating Pain Scale [NRPS]). All patients were evaluated by a blinded observer using the outcomes tests at enrollment (T0), after the treatment (T1) and at follow up 6 weeks later (T2). RESULTS: Both control and experimental groups evidenced an improvement of the outcomes after the treatment (MI, Ashworth and NRPS with P<0.05). The experimental group showed further improvements after the follow up (all outcomes with P<0.01). CONCLUSIONS: In the treatment of pain, disability and spasticity in upper limb after stroke, robot-assisted mobilization associated to PRM is as effective as traditional rehabilitation. CLINICAL REHABILITATION IMPACT: Robot-assisted treatment has an impact on upper limb motor function in stroke patients. PMID- 27406880 TI - The role of psychological well-being in multiple sclerosis rehabilitation. AB - BACKGROUND: In patients affected by multiple sclerosis (MS) the disabilities increase during the progression of the disease, with a negative impact on quality of life. Rehabilitation improves motor performances, but remains unclear the role of psychological variables on motor recovery. AIM: The aim of this study was to investigate the role of the psychological well-being during a rehabilitation care in MS patients with moderate to severe disability. DESIGN: Longitudinal study. SETTING: Outpatients in a Neurorehabilitation Unit of Pisa and Ferrara University Hospital. POPULATION: 93 subjects affected by MS with moderate to severe degree of impairment were recruited (43 male, 50 female; mean age 53+/-11.19 years). In relation to the Expanded Disability Status Scale (EDSS) score the sample was divided in two group: Group 1 with moderate impairment (EDSS 4-5.5) and Group 2 with severe impairment (EDSS 6-7). METHODS: Psychological and functional status was assessed before and after a motor rehabilitative treatment, appropriate to their clinical needs. Parameters collected were: Short Form 36, Patient Health Questionnaire, Fatigue Severity Scale, 6-minute walking test and 10-meter walking test. RESULTS: Mood disorders, low quality of life (QoL) and high perceived fatigue are characteristic symptoms in our sample. Results do not show a direct correlation with motor impairment. Mood improves in both groups, while walking endurance and speed ability recovers only in Group 1, on the contrary QoL improves only in Group 2. Regression analysis show that in Group 1 a better QoL predicts a higher motor recovery, whereas in Group 2 the improvement of walking endurance influences the subjective well-being at the discharge. CONCLUSIONS: Subjective well-being is related with the perception of the new condition of life. In less impaired patients psychological status can influence the liability toward rehabilitation treatment, while in more impaired patients motor recovery affect well-being. Therefore, the psychological counselling should be provided during the rehabilitation treatment in order to achieve a successful patients' care. CLINICAL REHABILITATION IMPACT: Our approach contributes to bring out the role of subjective factors on motor rehabilitation outcome and the functional recovery effect on the psychological well-being. The knowledge of subjective needs related to disability degree should be used to customize an appropriate care in MS patients. PMID- 27406881 TI - Vacuum synthesis of magnetic aluminum phthalocyanine on Au(111). AB - Air-unstable magnetic aluminum phthalocyanine (AlPc) molecules are prepared by an on-surface metalation reaction of phthalocyanine with aluminum (Al) atoms on Au(111) in ultrahigh vacuum. Experiments and density functional theory calculations show that an unpaired spin is located on the conjugated isoindole lobes of the molecule rather than at the Al position. PMID- 27406882 TI - Can skin cancer in humans be prevented by alleviation of oxidative stress? AB - The range of photon energies in solar radiation and the diverse cell and molecular targets in skin allow for participation of oxygen radicals and oxidative stress at several levels in the development of skin cancer: DNA damage and mutation, membrane damage, and intracellular signalling. The intense UVA component of sunlight (315-400 nm) is of particular interest because of deep penetration, generation of oxidative damage and having a mutational spectrum which overlaps that of the more carcinogenic UVB (280-315 nm). Many UV-induced mutagenic and signalling events are now understood at the molecular level, and significant protection from UV carcinogenesis has been obtained with antioxidants in experimental animals. There is little evidence to suggest, however, that similar results have been achieved in humans although the converse effect has been established, of elevated skin cancer risk following simultaneous exposure to sunlight and precursors of the pro-oxidant paraquat. The present difficulty in translating these findings to prevent human skin cancer may arise from deficiencies in the models used and incomplete information about the specific responses of the target cells relevant to solar UV. PMID- 27406883 TI - Radical approach to the acute respiratory distress syndrome. AB - The acute respiratory distress syndrome continues to be a major medical problem. Despite recent advances in treatment, such as the use of nitrogen monoxide (NO), extracorporeal membrane oxygenation (ECMO) and specialized ventilatory techniques in maintaining adequate oxygenation, mortality still remains high. The presence of activated neutrophils coupled with high inspired oxygen concentrations provide conditions that favour increased oxidative stress and this has focused attention on the possible role of free radical species in both the initiation and propagation of ARDS. Although there is evidence implicating increased free radical activity in ARDS, much of this is from animal models and the role of intervention in such processes has not been established. Although antioxidant therapy has been suggested as a possible treatment for ARDS the current literature is less than convincing. We examine the available data from human studies and suggest possible further studies and future therapeutic goals. PMID- 27406884 TI - Protein hydroperoxides as new reactive oxygen species. AB - There is convincing evidence for the involvement of Reactive Oxygen Species (ROS) in the initiation and development of various forms of damage in living organisms. Attempts to prevent or limit such damage have been largely unsuccessful, principally because most of the pathways linking the formation of ROS with the end-point pathology are unknown. Evidence summarized in this review suggests that proteins are the most likely initial targets of ROS in cells and that protein hydroperoxides are major products of this interaction. Recent research has shown that the protein hydroperoxides can in turn generate new free radicals, inactivate enzymes, destroy antioxidants, and crosslink with DNA. This suggests that protein hydroperoxides may constitute an important intermediate stage in the development of ROS-induced biological damage, and that they should therefore be regarded as a new form of reactive oxygen species. PMID- 27406885 TI - A monoclonal antibody recognizing the chlorohydrin derivatives of oleic acid for probing hypochlorous acid involvement in tissue injury. AB - A monoclonal antibody against hypochlorous acid-modified oleic acid has been raised to investigate involvement of HOCI in tissue injury. Mice were immunized with an isomeric mixture of chlorohydrin derivatives of oleic acid (18:0 chlorohydrin) conjugated to keyhole limpet haemocyanin (CH-KLH). The chlorohydrin was formed by the treatment of oleic acid with hypochlorous acid. Monoclonal antibodies were raised and the fusion was screened with 18:0-chlorohydrin-bovine serum albumin (CH-BSA) conjugate. A number of antibody-secreting clones were identified and the supernatants were characterized by binding studies and dose response curves. In ELISA, mAb CH-1 had an equivalent titre when either the chlorohydrin or bromohydrin derivative of oleic acid, complexed to bovine serum albumin, was used as screening antigen. The mAb CH-1 recognition of CH-BSA was competed with chlorohydrin and bromohydrin conjugates of BSA and KLH. Similarly, free 18:0-chlorohydrin and the 18:0-chlorohydrin-phosphatidyl choline treated with hypochlorous acid competed with mAb CH-1 binding. The mAb CH-1 also recognised the chlorohydrin derivative of linoleic acid and chlorohydrin formed from palmitoyl, oleyl phosphatidyl choline but with a decreased avidity. Weak cross-reactivity was observed with hydroxy-linoleic acid and linoleic acid hdroperoxide, either as free fatty acid or in phosphatidyl choline. There was minimal competitive binding of mAb CH-1 to free oleic acid, 16:0/18:1 phosphatidylcholine, cholesterol, or cholesterol chlorohydrin. The mAb CH-1 described here may be a useful probe for assessing the involvement of hypochlorous acid in tissue injury. PMID- 27406886 TI - Interactions between bilirubin and reactive oxygen species in liver microsomes and in human neutrophil granulocytes. AB - Bilirubin protects polyunsaturated fatty acids from lipid peroxidation, thus preventing damage by reactive oxygen species to cell membranes and proteins. On the other hand, such reactive oxygen species may contribute to the degradation and elimination of bilirubin. We therefore examined the interactions between bilirubin and reactive oxygen species. Bilirubin is decomposed in microsomes via a NADPH-independent process. This reaction appears to be mediated by H2O2 or by the hydroxyl radical since it is stimulated by exogenous H2O2 and by cytochrome P450 inducers, which increase H2O2 production in microsomes, and is inhibited by the hydroxyl radical scavenger sodium benzoate. These results suggest that cytochrome P450 may act as a peroxidase or as a Fenton catalyst in bilirubin degradation. On the other hand, bilirubin inhibits the NADPH consumption of microsomes as well as the NADPH oxidase activity of human neutrophil granulocytes and the resulting superoxide formation in these cells. This effect on superoxide concentration may be partially due to direct interaction between superoxide and bilirubin, since bilirubin reduces the superoxide concentration in a xanthine oxidase system. Bilirubin degradation is inhibited by superoxide dismutase suggesting that bilirubin may be oxidized in this system by the superoxide radical. The bilirubin-induced reduction in superoxide concentration in the supernatant of granulocytes suggests that hyperbilirubinemia may compromise immune function. PMID- 27406888 TI - Diary. PMID- 27406887 TI - Use of isotopically labelled spin-traps to determine definitively the presence or absence of non-radical addition artefacts in EPR spin-trapping systems. AB - EPR spin-trapping, although a powerful, sensitive technique for the study of free radicals, can be susceptible to artefacts; one of the most intractable to determine has been the non-radical addition of a substrate to a spin-trap followed by oxidation of the product to an EPR-detectable nitroxide. This work details how differentially isotopically labelled spin-traps (either nitroso or nitrone) may be used to determine the presence (or absence) of such artefacts, and provide a semi-quantitative measure of the extent of their contribution to the total EPR spectra in spin-trapping reactions. Artefactual 'ene' addition of the nitroso spin-trap 3,5-dibromo-4-nitroso-benzenesulphonic acid (DBNBS) to tryptophan followed by oxidation to EPR-detectable products has been confirmed, as has its nucleophilic addition to the thiol of glutathione to give non-EPR detectable products. The nitrone alpha-phenyl-N-tert-butylnitrone (PBN) exhibited no such reactivity. PMID- 27406889 TI - Multi-orbital quantum antiferromagnetism in iron pnictides-effective spin couplings and quantum corrections to sublattice magnetization. AB - Effective spin couplings and spin fluctuation induced quantum corrections to sublattice magnetization are obtained in the [Formula: see text] AF state of a realistic three-orbital interacting electron model involving xz, yz and xy Fe 3d orbitals, providing insight into the multi-orbital quantum antiferromagnetism in iron pnictides. The xy orbital is found to be mainly responsible for the generation of strong ferromagnetic spin coupling in the b direction, which is critically important to fully account for the spin wave dispersion as measured in inelastic neutron scattering experiments. The ferromagnetic spin coupling is strongly suppressed as the xy band approaches half filling, and is ascribed to particle-hole exchange in the partially filled xy band. The strongest AF spin coupling in the a direction is found to be in the orbital off-diagonal sector involving the xz and xy orbitals. First order quantum corrections to sublattice magnetization are evaluated for the three orbitals, and yield a significant [Formula: see text] average reduction from the Hartree-Fock value. PMID- 27406890 TI - Tunable switch mediated shikimate biosynthesis in an engineered non-auxotrophic Escherichia coli. AB - Shikimate is a key intermediate in the synthesis of neuraminidase inhibitors. Compared with traditional methods, microbial production of shikimate has the advantages of environmental friendliness, low cost, feed stock renewability, and product selectivity and diversity. Despite these advantages, shikimate kinase I and II respectively encoded by aroK and aroL are inactivated in most shikimate microbial producers, thus requiring the addition of aromatic compounds during the fermentation process. To overcome this problem, we constructed a non-auxotrophic, shikimate-synthesising strain of Escherichia coli. By inactivation of repressor proteins, blocking of competitive pathways and overexpression of key enzymes, we increased the shikimate production of wild-type E. coli BW25113 to 1.73 g/L. We then designed a tunable switch that can conditionally decrease gene expression and substituted it for the original aroK promoters. Expression of aroK in the resulting P-9 strain was maintained at a high level during the growth phase and then reduced at a suitable time by addition of an optimal concentration of inducer. In 5-L fed-batch fermentation, strain P-9 produced 13.15 g/L shikimate without the addition of any aromatic compounds. The tunable switch developed in this study is an efficient tool for regulating indispensable genes involved in critical metabolic pathways. PMID- 27406891 TI - Domain wall pinning in FeCoCu bamboo-like nanowires. AB - The three dimensional nature of cylindrical magnetic nanowires has opened a new way to control the domain configuration as well as the magnetization reversal process. The pinning effect of the periodic diameter modulations on the domain wall propagation in FeCoCu individual nanowires is determined by Magnetic Force Microscopy, MFM. A main bistable magnetic configuration is firstly concluded from MFM images characterized by the spin reversal between two nearly single domain states with opposite axial magnetization. Complementary micromagnetic simulations confirm a vortex mediated magnetization reversal process. A non-standard variable field MFM imaging procedure allows us to observe metastable magnetic states where the propagating domain wall is pinned at certain positions with enlarged diameter. Moreover, it is demonstrated that it is possible to control the position of the pinned domain walls by an external magnetic field. PMID- 27406892 TI - Iterative Exponential Growth Synthesis and Assembly of Uniform Diblock Copolymers. AB - Studies on the phase segregation of unimolecular block copolymers (BCPs) are limited by a lack of reliable, versatile methods for the synthesis of such polymers on the preparative scale. Herein, we describe an advancement of Iterative Exponential Growth (IEG) wherein chiral allyl-based IEG oligomers are subjected to thiol-ene reactions and converted into unimolecular BCPs. With this strategy we have synthesized uniform BCPs with molar masses up to 12.1 kDa on ~1 g scale. BCPs composed of decane-based side chains and either triethyleneglycol- or thioglycerol-based side chains phase-segregate into hexagonal cylinder morphologies. The assembly is not driven by side-chain crystallization, but is instead the result of amorphous BCP assembly. PMID- 27406894 TI - Physicochemical characterization of atorvastatin calcium/ezetimibe amorphous nano solid dispersions prepared by electrospraying method. AB - In the present study, electrospraying was applied as a novel method for the fabrication of amorphous nano-solid dispersions (N-SDs) of atorvastatin calcium (ATV), ezetimibe (EZT), and ATV/EZT combination as poorly water-soluble drugs. N SDs were prepared using polyvinylpyrrolidone K30 as an amorphous carrier in 1:1 and 1:5 drug to polymer ratios and the total solid (including drug and polymer) concentrations of 10 and 20% (w/v). The prepared formulations were further investigated for their morphological, physicochemical, and dissolution properties. Scanning electron microscopy studies indicated that the morphology and diameter of the electrosprayed samples (ESs) were influenced by the solution concentration and drug:polymer ratio, so that an increase in the solution concentration resulted in fiber formation while an increase in the polymer ratio led to enhancement of the particle diameter. Differential scanning calorimetry and X-ray powder diffraction studies together with in vitro dissolution test revealed that the ESs were present in an amorphous form with improved dissolution properties. Infrared spectroscopic studies showed hydrogen-bonding interaction between the drug and polymer in ESs. Since the electrospraying method benefits from the both amorphization and nanosizing effect, this novel approach seems to be an efficient method for the fabrication of N-SDs of poorly water-soluble drugs. PMID- 27406895 TI - An electron poor iridium pincer complex for catalytic alkane dehydrogenation. AB - A novel electron deficient 4,6-bis(trifluoromethyl)-1,3-phenylene diphosphinite ligand 4 was developed and synthesized. Reaction of Ir precursors with ligand 4 gave chloro(hydride) pincer complex 5, which demonstrated a higher TON in alkane dehydrogenation reactions compared to similar phosphinite based pre-catalysts. The formation of cyclooctene (COE) and tert-butylethylene adducts of the 14e catalysts was also studied and the COE adduct is implicated as the resting state of the catalyst. All compounds were characterized by NMR spectroscopy and, in addition, the molecular structures of key complexes were confirmed by X-ray analysis. PMID- 27406893 TI - Direct evidence of specific localization of sesquiterpenes and marchantin A in oil body cells of Marchantia polymorpha L. AB - Liverworts are a rich source of a diverse array of specialized metabolites, such as terpenoids and benzenoids, which are potentially useful for pharmaceutical or agrochemical applications, and also provide clues to elucidate the strategy by which liverworts adapt to the terrestrial environment. Liverworts, belonging to orders Marchantiales and Jungermanniales, possess oil bodies. In Marchantia polymorpha L., oil bodies are confined to scattered idioblastic oil body cells. It has been assumed that the specialized metabolites in M. polymorpha specifically accumulate in the oil bodies in oil body cells; however, no direct evidence was previously available for this specific accumulation. In this study, direct evidence was obtained using micromanipulation techniques coupled with MS analysis that demonstrated the specific accumulation of sesquiterpenoids and marchantin A in the oil body cells of M. polymorpha thalli. It was also observed that the number of oil body cells increased in thalli grown in low-mineral conditions. The amounts of sesquiterpenoids and marchantin A detected in crude extract prepared from the whole thallus were roughly proportional to the number of oil body cells found in a given volume of thallus, suggesting that oil body cell differentiation and sesquiterpenoid and marchantin A biosynthetic pathways are coordinated with each other. PMID- 27406896 TI - Origin of bimodal fluorescence enhancement factors of Chlorobaculum tepidum reaction centers on silver island films. AB - We focus on the spectral dependence of plasmon-induced enhancement of fluorescence of Chlorobaculum tepidum reaction centers. When deposited on silver island film, they exhibit up to a 60-fold increase in fluorescence. The dependence of enhancement factors on the excitation wavelength is not correlated with the absorption spectrum of the plasmonic structure. In particular, the presence of one (or multiple) trimers of the Fenna-Matthews-Olson (FMO) protein reveals itself in bimodal distribution of enhancement factors for the excitation at 589 nm, the wavelength corresponding to bacteriochlorophyll absorption of FMO and the core of the RC. We conclude that the structure of multichromophoric complexes can substantially affect the impact of plasmonic excitations, which is important in the context of assembling functional biohybrid systems. PMID- 27406897 TI - SINODAR ONE, an ongoing randomized clinical trial to assess the role of axillary surgery in breast cancer patients with one or two macrometastatic sentinel nodes. AB - Sentinel lymph node biopsy alone is the current surgical axillary treatment for early-stage breast cancer patients with a negative sentinel lymph node (SLN). The possibility to omit axillary dissection also in presence of positive SLNs has been promoted by the American College of Surgeons Oncology Group (ASOCOG) Z0011 randomized trial. Several limitations and evidences of potential selection bias made this trial fairly controversial. Stronger evidence than currently available is needed on the safety of foregoing axillary dissection in well-defined populations of patients with positive SLNs. The Italian multicentre SINODAR ONE randomized trial here presented was designed with this aim. PMID- 27406898 TI - Three-dimensional mapping of the arteriovenous loop model using two-dimensional histological methods. AB - OBJECTIVES: The aim of this study was to create an analytical tool for the three dimensional distribution of immunohistochemically stained cells in the arteriovenous (AV) loop model of the femoral vessels of rats that fuses two dimensional histological slides into stacks. METHODS: A total of 22 AV loops were implanted into male syngeneic Lewis rats by creating an arteriovenous fistula between the femoral artery and vein by interposing a femoral vein graft of the contralateral extremity. This fistula was embedded into an isolation chamber filled with a fibrin matrix. Specimens were explanted after 7 to 14 days, and the AV loop was processed using standard histological protocols. Immunohistochemical staining for HIF-1alpha and a counter staining with hematoxylin was performed. Various layouts with different cutting planes, regions of interest, and post processing algorithms were evaluated. Results and observations: The proximal-to distal cutting perpendicular to the vascular axis proved to be the best layout for mapping the three-dimensional constructs containing the AV loop. A semi automatic algorithm for the differentiation of immunohistochemical positive and negative cells was developed. CONCLUSION: The newly established methods from this study constitute an excellent tool for the general evaluation of the AV loop model - particularly with regard to the three-dimensional distribution of immunohistochemical positive and negative cells. PMID- 27406899 TI - Marginal bone loss around implants with platform-switched Morse-cone connection: a radiographic cross-sectional study. AB - OBJECTIVES: The aims of the present cross-sectional study are to evaluate the bone remodeling around Morse-cone implants placed subcrestally 1 year after loading and the prevalence of bone loss >0.5 mm after at least 3 years of loading. MATERIAL AND METHODS: Subjects who underwent a radiographic check in 2013 with implants that had been in function for at least 3 years were considered for inclusion. The study population comprised of 145 subjects with a total of 523 implants. At the moment of insertion, all the implants were placed subcrestally from 1 to 3 mm as clinically measured. Radiographs taken at baseline, that is 1 year after loading (T0), and at the follow-up visit in 2013 (T1) were examined. The distance between the rim of the implant and the marginal bone level at mesial and distal aspects of each implant was determined and the mean bone loss calculated. RESULTS: In the total sample, the mean bone loss occurred between baseline and 2013 examination was 0.42 +/- 0.77 mm; at T1 424 implants presented the marginal bone level at the implant rim (78) or above it (346). On the other hand, 99 implants presented the rim above the bone crest. Fifty-one implants that at T1 presented the rim above the bone crest, and that between T0 and T1 had lost at least 0.5 mm, were considered losers: 10 implants lost up to 0.5 mm, 11 lost from 0.6 to 1 mm, 16 lost from 1.1 to 2 mm, and 14 lost more than 2 mm of bone. On a subject basis, 34 subjects (group A) with a total of 200 implant sites presented loser implants, while 111 subjects (group B) with 323 implants displayed non-loser implants. CONCLUSIONS: Within the limits of a cross-sectional study, the results show that Morse-cone implants placed subcrestally in the vast majority of cases (89.9%) are able to maintain the bone crest at level of the rim or above it 1 year after loading. The incidence of loser sites (bone loss >0.5 mm) after at least 3 years of follow-up is 9.7% at implant level and 23.5% at patient level. PMID- 27406900 TI - E3 ubiquitin ligase: A potential regulator in fibrosis and systemic sclerosis. AB - Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis in the skin and internal organs. The pathogenesis of SSc is not completely understood until now. Recently, many studies have focused on the role of E3 ubiquitin ligases in organ fibrosis. However, the possible regulatory mechanisms of E3 ubiquitin ligases in fibrosis and SSc are not well documented. In this review, we summarized that E3 ubiquitin ligases regulated fibrosis through ubiquitin-mediated degradation of TGF-beta/Smad signaling pathway. Moreover, E3 ubiquitin ligases participated in regulating fibrosis by other methods, such as inducing epithelial transition to mesenchymal cell, enhancing the production of TGF-beta and protecting activated hepatic stellate cells from apoptosis. However, the specific regulatory mechanisms of E3 ubiquitin ligases in scleroderma is still not fully understood. There are more works to be done to specify the mechanism of E3 ubiquitin ligases in regulation of fibrosis in SSc. PMID- 27406901 TI - A universal design for a DNA probe providing ratiometric fluorescence detection by generation of silver nanoclusters. AB - DNA-stabilized silver nanoclusters (AgNCs), the fluorescence emission of which can rival that of typical organic fluorophores, have made possible a new class of label-free molecular beacons for the detection of single-stranded DNA. Like fluorophore-quencher molecular beacons (FQ-MBs) AgNC-based molecular beacons (AgNC-MBs) are based on a single-stranded DNA that undergoes a conformational change upon binding a target sequence. The new conformation exposes a stretch of single-stranded DNA capable of hosting a fluorescent AgNC upon reduction in the presence of Ag(+) ions. The utility of AgNC-MBs has been limited, however, because changing the target binding sequence unpredictably alters cluster fluorescence. Here we show that the original AgNC-MB design depends on bases in the target-binding (loop) domain to stabilize its AgNC. We then rationally alter the design to overcome this limitation. By separating and lengthening the AgNC stabilizing domain, we create an AgNC-hairpin probe with consistent performance for arbitrary target sequence. This new design supports ratiometric fluorescence measurements of DNA target concentration, thereby providing a more sensitive, responsive and stable signal compared to turn-on AgNC probes. Using the new design, we demonstrate AgNC-MBs with nanomolar sensitivity and singe-nucleotide specificity, expanding the breadth of applicability of these cost-effective probes for biomolecular detection. PMID- 27406902 TI - Biomechanical and fluid flowing characteristics of intervertebral disc of lumbar spine predicted by poroelastic finite element method. AB - PURPOSE: This study is to reveal the deformation of intervertebral disc (IVD), the stress distribution of solid phase and liquid phase, the variation of fluid flux and flow velocity in lumbar spine and the influence of different permeability parameters on them under intermittent compressive loading. METHODS: A poroelastic FEM of L4-L5 is assigned with different permeability parameters to analyze the deformation, stress distribution and fluid convection under intermittent compressive loads. RESULTS: The results show that the pore pressure of IVD decreases with time, but the effective stress increases under intermittent compressive loads. The axial and radial strain will increase and fluid loss will recover at a more rapid rate if the permeability of endplate increases during unloading period. The velocity vectors show that most of the liquid in the disc flows into vertebrae through endplates and only a small quantity of liquid flows through the annulus fibrosus at the loading step, however, at the unloading step, almost all the liquid flowing into IVD is through the endplates. CONCLUSIONS: The changing rate of pore pressure and effective stresses of nucleus pulposus and annulus fibrosus with higher permeability is smaller than that with smaller permeability. The degenerated endplate (with low permeability) yields high flow velocity decreasing gradient, which might impede liquid inflowing/outflowing smoothly through the endplates. The fluid flowing velocity in loading phase is faster than that in unloading phase, so a short resting time can relieve fatigue, but could not recover to the original liquid condition in IVDs. PMID- 27406903 TI - Structure elucidation and biological activity of antibacterial compound from Micromonospora auratinigra, a soil Actinomycetes. AB - AIMS: The aim of this study was to isolate and characterize the bioactive compound of Micromonospora auratinigra, HK-10 and its antibacterial inhibitory mechanism. METHODS AND RESULTS: An oily bioactive compound was extracted from HK 10 (GenBank accession no. JN381554) and found to have promising antibacterial activity. The compound was characterized as 2-methylheptylisonicotinate (1) by (1) H, (13) C NMR and mass spectroscopy. Minimum inhibitory concentration (MIC) of this molecule was tested by micro broth dilution method and was found to be 70, 40, 80, 60, 60 and 50 MUg for Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, Echerichia coli, Pseudomonas aeruginosa and Mycobacterium abscessus respectively. The effects of compound 1 were studied on bacterial membrane structure using scanning electron microscopy. The results indicated a membrane-disrupting mechanism, resulting in the dysfunction of the cytoplasmic membrane structure and cell death of the pathogenic bacterial strains. Kinetics of growth of the test organisms was also analysed and indicated 2 methylheptylisonicotinate 1 as a bactericidal agent. Furthermore, we have studied the binding affinity of 1 towards different membrane proteins of pathogenic bacteria by in silico analysis. CONCLUSIONS: 2-methylheptylisonicotinate was isolated from M. auratinigra, a rare actinobacterial strain possessing antibacterial activity through a membrane-disrupting mechanism, and has MICs similar to standard antibiotic neomycin sulphate. It is the first report about a strain of M. auratinigra, isolated from Indo-Burma biodiversity hotspot of North east India with new antimicrobial activities. In silico studies have also supported these results performed on various membrane targets of pathogenic bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The antibacterial potential of M. auratinigra is reported for the first time. The results indicate the possible use of 2-methylheptylisonicotinate as a source of antibacterial agent against dreaded human pathogens. PMID- 27406904 TI - Influence of Metal Diboride and Dy2O3 Additions on Microstructure and Properties of MgB2 Fabricated at High Temperatures and under Pressure. AB - High temperatures and under pressure (HTP) processing has been used to study the effects of chemical doping in MgB2. ZrB2, TiB2 and NbB2 were selected as additives since, like MgB2, they have an AlB2-type structure and similar lattice parameters. Dy2O3 was selected as it has been reported to generate nanoscale, secondary intragrain phases in MgB2. While C is known to enter the B-sublattice readily, attempts to dope Zr and other elements onto the Mg site have been less successful due to slow bulk diffusion, low solubility in MgB2, or both. We have used high-temperature, solid-state sintering (1500 degrees C), as well as excursions through the peritectic temperature (up to 1700 degrees C), to investigate both of these limitations. Bulk MgB2 samples doped with MB2 (M = Zr, Ti and Nb) and Dy2O3 additions were synthesized and then characterized. Lattice distortion and high densities of crystal defects were observed in the MgB2 grains around nano-sized MB2 inclusions, this highly defected band contributed to a large increase in Bc2 but was not large enough to increase the irreversibility field. In contrast, distributed intragrain precipitates were formed by Dy2O3 additions which did not change the lattice parameters, Tc, Tc distribution or Bc2 of MgB2, but modified the flux pinning. PMID- 27406905 TI - Interplay between Clinical Guidelines and Organizational Workflow Systems. Experience from the MobiGuide Project. AB - BACKGROUND: Implementing a decision-support system within a healthcare organization requires integration of clinical domain knowledge with resource constraints. Computer-interpretable guidelines (CIG) are excellent instruments for addressing clinical aspects while business process management (BPM) languages and Workflow (Wf) engines manage the logistic organizational constraints. OBJECTIVES: Our objective is the orchestration of all the relevant factors needed for a successful execution of patient's care pathways, especially when spanning the continuum of care, from acute to community or home care. METHODS: We considered three strategies for integrating CIGs with organizational workflows: extending the CIG or BPM languages and their engines, or creating an interplay between them. We used the interplay approach to implement a set of use cases arising from a CIG implementation in the domain of Atrial Fibrillation. To provide a more scalable and standards-based solution, we explored the use of Cross-Enterprise Document Workflow Integration Profile. RESULTS: We describe our proof-of-concept implementation of five use cases. We utilized the Personal Health Record of the MobiGuide project to implement a loosely-coupled approach between the Activiti BPM engine and the Picard CIG engine. Changes in the PHR were detected by polling. IHE profiles were used to develop workflow documents that orchestrate cross-enterprise execution of cardioversion. CONCLUSIONS: Interplay between CIG and BPM engines can support orchestration of care flows within organizational settings. PMID- 27406906 TI - A model to predict anti-tuberculosis activity: value proposition for marine microorganisms. AB - The development of new antibiotics effective against all strains of tuberculosis (TB) is needed. To evaluate the potential of marine microbe-derived natural products as anti-TB leads, we analyzed and compared the physico-chemical properties of 39 current TB drugs and candidates against 60 confirmed mycobacteria-active natural products. We showed that anti-TB natural products sourced from marine microbes have a large overlap with TB drug-like space. A model to predict potential anti-TB drugs is proposed. PMID- 27406908 TI - New cytotoxic trichothecene macrolide epimers from endophytic Myrothecium roridum IFB-E012. PMID- 27406907 TI - Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027. AB - Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site directed mutagenesis of the conserved residues lining this site allowed us to propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase associated enzymes, into an enzyme-sequestered enediyne core intermediate. These findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis. PMID- 27406912 TI - Endocannabinoid Regulation of Cocaine Reinforcement: an Upper or Downer? PMID- 27406913 TI - Biological Functionalization of Conjugated Polymer Nanoparticles for Targeted Imaging and Photodynamic Killing of Tumor Cells. AB - Conjugated polymer nanoparticles composed of PFT/PS as a core and PEG-COOH on the surface were prepared by a reprecipitating method. The CPNs diaplay excellet properties such as good photostability, low cytotoxicity, and strong brightness, etc. The average diamater of CPNs is 30 nm with a spherical morphology. To realize specific imaging in different parts of tumor cells, the bare CPNs with the carboxyls on the surface were conjugated with antibody or peptide by a covalent mode. Studies display that CPNs modified with anti-EpCAM can recognize MCF-7 tumor cells and locate on the membrane, while CPNs conjugated with transcriptional activator protein (Tat) specifically locate in the cytoplasm of MCF-7 cells. On the basis of the ability of CPNs for producing reactive oxygen species (ROS) under light irradiation, photodynamic therapy for tumor cells was investigated. Due to the long distance and wide diffusion range, MCF-7 tumor cells with CPNs/anti-EpCAM have no obvious change with or without white light irradiation. However, CPNs/Tat exhibits higher killing ability for MCF-7 cells. Noticeably, multifunctional CPNs linked with anti-EpCAM and Tat simultaneously not only can specifically target MCF-7 tumor cells, but also may inhibit and kill these cells. This work develops a potential application platform for multifunctional CPNs in locating imaging, photodynamic therapy, and other aspects. PMID- 27406914 TI - Outcomes of induced versus spontaneous labor. AB - PURPOSE: Induced labor is associated with a higher request for analgesia than spontaneous labor. This study compared duration of labor, mode of delivery, quantity of blood loss, type of perineal outcome and neonatal outcomes between women in induced labor and women in spontaneous labor, both on epidural analgesia (administered at cervical dilation <= 4 cm). METHODS: In a two-year longitudinal cohort study, data were gathered from nulliparous women with a single cephalic pregnancy of at least 37 weeks attending the labor and delivery ward in Policlinico San Matteo Fundation-Pavia. Data were compared for women with early labor analgesia in (1) spontaneous labor (Robson group 1) and (2) induced labor (dinoprostone - vaginal insert or gel, Robson group 2a). RESULTS: Of the 1104 women who underwent epidural analgesia in the study period, 531 were included: 326 in spontaneous labor and 205 in induced labor. The only significant difference found was duration of the first stage, which lasted 305 (200-390) min in spontaneous labor compared to 205 min (120-345) in induced labor (p <0.001). CONCLUSIONS: In women on early epidural analgesia, induction is associated with a shorter duration of the first stage of labor and does not affect other outcomes. PMID- 27406915 TI - Recognition of a novel HLA-A*11 variant, HLA-A*11:196, in a Taiwanese unrelated bone marrow stem cell donor. AB - One nucleotide substitution at residue 484 of HLA-A*11:01:01:01 results in a novel allele, HLA-A*11:196. PMID- 27406917 TI - Repulsive van der Waals forces enable Pickering emulsions with non-touching colloids. AB - Emulsions stabilized by solid particles, called Pickering emulsions, offer promising applications in drug delivery, cosmetics, food science and the manufacturing of porous materials. This potential stems from their high stability against coalescence and 'surfactant-free' nature. Generally, Pickering emulsions require that the solid particles are wetted by both phases and as a result, the adsorption free energy is often large with respect to the thermal energy (kBT). Here we provide the first experimental proof for an alternative scenario: non touching (effectively non-wetting), charged, particles that are completely immersed in the oil phase through a balance of charge induced attractions and repulsions caused by van der Waals forces. These particles nonetheless stabilize the emulsion. The main advantage of this novel adsorption mechanism is that these particles can easily be detached from the interface simply by adding salt. This not only makes the finding fundamentally of interest, but also enables a triggered de-emulsification and particle recovery, which is useful in fields like enhanced oil recovery, heterogeneous catalysis, and emulsion polymerization. PMID- 27406916 TI - Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti inflammatory arginase 2 expression in macrophages. AB - Mer signaling increases the transcriptional activity of liver X receptor (LXR) to promote the resolution of acute sterile inflammation. Here, we aimed to understand the pathway downstream of Mer signaling after growth arrest-specific protein 6 (Gas6) treatment that leads to LXR expression and transcriptional activity in mouse bone-marrow derived macrophages (BMDM). Gas6-induced increases in LXRalpha and LXRbeta and expression of their target genes were inhibited in BMDM from STAT1(-/-) mice or by the STAT1-specific inhibitor fludarabine. Gas6 induced STAT1 phosphorylation, LXR activation, and LXR target gene expression were inhibited in BMDM from Mer(-/-) mice or by inhibition of PI3K or Akt. Gas6 induced Akt phosphorylation was inhibited in BMDM from STAT1(-/-) mice or in the presence of fludarabine. Gas6-induced LXR activity was enhanced through an interaction between LXRalpha and STAT1 on the DNA promoter of Arg2. Additionally, we found that Gas6 inhibited lipopolysaccharide (LPS)-induced nitrite production in a STAT1 and LXR pathway-dependent manner in BMDM. Additionally, Mer neutralizing antibody reduced LXR and Arg2 expression in lung tissue and enhanced NO production in bronchoalveolar lavage fluid in LPS-induced acute lung injury. Our data suggest the possibility that the Gas6-Mer-PI3K/Akt-STAT1-LXR-Arg2 pathway plays an essential role for resolving inflammatory response in acute lung injury. PMID- 27406920 TI - Pain management in fibromyalgia. PMID- 27406919 TI - A position statement on the management of patients with pityriasis rosea. AB - Many clinical trials have been conducted on the treatment of pityriasis rosea (PR). Our aim was to establish a position statement for the management of adults with PR based on the best available evidence. We searched PubMed for all reports on randomized controlled trials for the treatment of PR published in the past 30 years. We retrieved 14 articles reporting randomized controlled trials, and found five which met our quality requirements for in-depth analyses. Erythromycin was found in a well-conducted triple-blind study to cast significant impacts on clinical outcomes. However, adverse gastrointestinal effects were fairly common. Another well-conducted study on azithromycin reported no significant benefit. It was reported in three well-conducted studies on oral acyclovir in low dose (400 mg three times daily for 7 days or 400 mg five times daily for 7 days) and high dose (800 mg five times daily for 7 days), that acyclovir is effective in attaining rash regression and lessening the pruritus. When compared against each other, the high-dose regimen demonstrated no benefit over the low-dose regimens. Our statement comprises the follows: (i) The diagnosis of PR should be ascertained; (ii) The patients should be assessed for rash severity and impacts on quality of life; (iii) PR is a self-limiting disease, and most patients do not necessitate any treatment; (iv) For patients necessitating active treatment, oral acyclovir as 400 mg three times daily for 7 days can be considered; (v) Attention should be given to adverse effects and contraindications of acyclovir; (vi) When PR occurs in early pregnancy, oral antiviral therapy could be considered after consulting experienced clinicians; (vii) Inadequate information exists in the use of acyclovir to treatment PR in children and breastfeeding women; and (viii) Treating PR is an off-label use of acyclovir, and this has to be discussed with experienced colleagues and the patients. PMID- 27406922 TI - A Core-Shell Fe/Fe2 O3 Nanowire as a High-Performance Anode Material for Lithium Ion Batteries. AB - The preparation of novel one-dimensional core-shell Fe/Fe2 O3 nanowires as anodes for high-performance lithium-ion batteries (LIBs) is reported. The nanowires are prepared in a facile synthetic process in aqueous solution under ambient conditions with subsequent annealing treatment that could tune the capacity for lithium storage. When this hybrid is used as an anode material for LIBs, the outer Fe2 O3 shell can act as an electrochemically active material to store and release lithium ions, whereas the highly conductive and inactive Fe core functions as nothing more than an efficient electrical conducting pathway and a remarkable buffer to tolerate volume changes of the electrode materials during the insertion and extraction of lithium ions. The core-shell Fe/Fe2 O3 nanowire maintains an excellent reversible capacity of over 767 mA h g(-1) at 500 mA g(-1) after 200 cycles with a high average Coulombic efficiency of 98.6 %. Even at 2000 mA g(-1) , a stable capacity as high as 538 mA h g(-1) could be obtained. The unique composition and nanostructure of this electrode material contribute to this enhanced electrochemical performance. Due to the ease of large-scale fabrication and superior electrochemical performance, these hybrid nanowires are promising anode materials for the next generation of high-performance LIBs. PMID- 27406921 TI - Aquaglyceroporin function in the malaria mosquito Anopheles gambiae. AB - BACKGROUND INFORMATION: Anopheles gambiae is the major mosquito vector for Plasmodium falciparum malaria in sub-Saharan Africa, where it survives in stressful climates. Aquaporin water channels are expressed in all life forms, where they provide environmental adaptation by conferring rapid trans-cellular movement of water (classical aquaporins) or water plus glycerol (aquaglyceroporins). Here, we report an aquaglyceroporin homolog in A. gambiae, AgAQP3 (A. gambiae aquaglyceroporin 3). RESULTS: Despite atypical pore-lining amino acids, AgAQP3 is permeated by water, glycerol and urea, and is not significantly inhibited by 1 mM HgCl2 . AgAQP3 is expressed more heavily in male mosquitoes, yet adult female A. gambiae abundantly express AgAQP3 in Malpighian tubules and gut where large amounts of fluid exchange occur during blood meal digestion, water and nutrient absorption and waste secretion. Reducing expression of AgAQP3 by RNA interference reduces median mosquito survival at 39 degrees C. After an infectious blood meal, mosquitoes with depleted AgAQP3 expression exhibit fewer P. falciparum oocysts in the midgut compared to control mosquitoes. CONCLUSIONS: Our studies reveal critical contributions of AgAQP3 to A. gambiae heat tolerance and P. falciparum development in vivo. SIGNIFICANCE: This study indicates that AgAQP3 may be a major factor explaining why A. gambiae is an important malaria vector mosquito in sub-Saharan Africa, and may be a potential target for novel malaria control strategies. PMID- 27406923 TI - Nutritional and non-nutritional food components modulate phenotypic variation but not physiological trade-offs in an insect. AB - Our understanding of how food modulates animal phenotypes and mediate trade-offs between life-history traits has benefited greatly from the study of combinations of nutritional and non-nutritional food components, such as plant secondary metabolites. We used a fruit fly pest, Anastrepha ludens, to examine phenotypic variation across larval, pupal and adult stages as a function of larval food with varying nutrient balance and content of chlorogenic acid, a secondary metabolite. Larval insects that fed on carbohydrate-biased diets relative to protein exhibited longer larval and pupal developmental periods, were often heavier as pupae and resisted desiccation and starvation for longer periods in the adult stage than insects fed on highly protein-biased diets. Except for a potential conflict between pupal development time and adult desiccation and starvation resistance, we did not detect physiological trade-offs mediated by the nutritional balance in larval food. Chlorogenic acid affected A. ludens development in a concentration and nutrient-dependent manner. Nutrients and host plant secondary metabolites in the larval diet induced changes in A. ludens phenotype and could influence fruit fly ecological interactions. We provide a unique experimental and modelling approach useful in generating predictive models of life history traits in a variety of organisms. PMID- 27406925 TI - Kinetic and Conformational Insights of Protein Adsorption onto Montmorillonite Revealed Using in Situ ATR-FTIR/2D-COS. AB - Protein adsorption onto clay minerals is a process with wide-ranging impacts on the environmental cycling of nutrients and contaminants. This process is influenced by kinetic and conformational factors that are often challenging to probe in situ. This study represents an in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic investigation of the adsorption of a model protein (bovine serum albumin (BSA)) onto a clay mineral (montmorillonite) at four concentrations (1.50, 3.75, 7.50, and 15.0 MUM) under environmentally relevant conditions. At all concentrations probed, FTIR spectra show that BSA readily adsorbs onto montmorillonite. Adsorption kinetics follow an Elovich model, suggesting that primary limitations on adsorption rates are surface-related heterogeneous energetic restrictions associated with protein rearrangement and lateral protein-protein interaction. BSA adsorption onto montmorillonite fits the Langmuir model, yielding K = 5.97 * 10(5) M(-1). Deconvolution and curve fitting of the amide I band at the end of the adsorption process (~120 min) shows a large extent of BSA unfolding upon adsorption at 1.50 MUM, with extended chains and turns increasing at the expense of alpha-helices. At higher concentrations/surface coverages, BSA unfolding is less pronounced and a more compact structure is assumed. Two-dimensional correlation spectroscopic (2D-COS) analysis reveals three different pathways corresponding to adsorbed conformations. At 1.50 MUM, adsorption increases extended chains, followed by a loss in alpha-helices and a subsequent increase in turns. At 3.75 MUM, extended chains decrease and then aggregated strands increase and side chains decrease, followed by a decrease in turns. With 7.50 and 15.0 MUM BSA, the loss of side chain vibrations is followed by an increase in aggregated strands and a subsequent decrease in turns and extended chains. Overall, the BSA concentration and resultant surface coverage have a profound impact on the dynamics of BSA adsorption onto montmorillonite. These results enhance our understanding of the molecular-level protein dynamics and stabilization of organic matter at mineral surfaces. PMID- 27406924 TI - Response to letter to the Editor: Reliability of lumbar movement dysfunction tests for chronic low back pain patients; methodological concerns to avoid misinterpretation. PMID- 27406926 TI - Trends in the diagnosis of bipolar disorder: Has the story changed? AB - OBJECTIVE: A recent study reported an 8% increase in bipolar diagnoses in public and community mental health services in New South Wales from 2003 to 2014, an increase interpreted by the authors as reflecting increasing diagnostic boundaries of bipolar disorder, and bipolar II in particular. If valid, we would expect an increase in hospital admissions for hypomania as well as for mania and so analysed a relevant dataset to test that hypothesis. METHODS: Data were examined for 27,255 individuals hospitalised in NSW psychiatric hospitals over a 14-year period (2000-2014) for ICD-10 diagnosed mania or hypomania and with analyses examining rates of hospitalisation/per year for both mania and for hypomania. RESULTS: While overall admissions for mania and hypomania increased over the study period by 16.4%, admissions for mania increased by 31.0% and admissions for hypomania actually decreased by 32.1%. CONCLUSION: The increased rate in admissions of those with a bipolar disorder appears to reflect a trend over more than four decades. The hypothesis that any increase in the diagnostic boundaries of bipolar II disorder would be associated with an increase in hospitalisation rates was rejected, with the converse trend being identified. PMID- 27406927 TI - Mania associated with self-prescribed acetyl-l-carnitine in a man with bipolar I disorder. AB - OBJECTIVE: Complementary medicines are readily available and becoming increasingly popular. Acetyl-l-carnitine (ALC) is widely recognised as a safe dietary supplement to aid weight loss. We present the case of a patient who had a relapse of mania in the context of ALC use for weight loss over a two week period, on the background of bipolar I disorder previously in remission. The patient's symptoms resolved a few days after ALC was ceased. CONCLUSIONS: Given the high rates of obesity among people with mental illness, it is possible ALC may be utilised in the hope of aiding weight loss. This case highlights the importance of psychiatrists maintaining open communication with their patients about use of complementary medicines, and the risks and benefits of their use. PMID- 27406928 TI - Lifetime rates and correlates of crime victimisation in young people with mental ill-health. AB - OBJECTIVE: Research on crime victimisation in the mentally ill has focused on middle aged cohorts with long-standing illness and functional disability. The rates and correlates of victimisation in young cohorts is largely unknown. METHODS: Participants ( n=776) were aged 12-25 years attending headspace centres in Australia, who consented to a clinical interview and provided self-reported data regarding lifetime victimisation. RESULTS: A quarter of the sample (24.5%) reported crime victimisation, including 18.5% who experienced violent victimisation (mainly physical or sexual assault) and 14.1% non-violent crime. Both forms of victimisation were associated with illicit substance use, sexual orientation, and young adult age, while male gender was specifically associated with non-violent victimisation. Participants who reported violent victimisation were significantly more impaired both functionally and clinically than those reporting non-violent victimisation or no victimisation. CONCLUSIONS: Young people with mental ill-health are vulnerable to criminal victimisation, particularly violent assaults, although the lifetime rates of victimisation are substantially lower than those observed in older cohorts with serious mental illness. Effective, early intervention to address modifiable factors may reduce the risk of further victimisation. PMID- 27406929 TI - Managing melancholic depression: a personal perspective. AB - OBJECTIVES: The objective of this article is to offer a personal perspective on managing melancholia by interpreting both the limited salient evidence base and offering clinical observations. CONCLUSIONS: It is suggested that medication needs to be prioritised, that not all antidepressants are equally potent for those with melancholia and that as response to a single antidepressant alone (especially a narrow-spectrum one) is low, management commonly requires broader spectrum antidepressant drugs and augmentation strategies. PMID- 27406930 TI - Comorbidity Action in the North: a study of services for people with comorbid mental health and drug and alcohol disorders in the northern suburbs of Adelaide. AB - OBJECTIVE: This study identified barriers to and facilitators of mental health (MH) and alcohol and drug (AOD) comorbidity services, in order to drive service improvement. METHOD: Participatory action research enabled strong engagement with community services, including Aboriginal and refugee groups. Surveys, interviews and consultations were undertaken with clinicians and managers of MH, AOD and support services, consumers, families, community advocates and key service providers. Community participation occurred through consultation, advisory and working party meetings, focus groups and workshops. RESULTS: Barriers included inadequate staff training and poor community and workforce knowledge about where to find help. Services for Aboriginal people, refugees, the elderly and youth were inadequate. Service fragmentation ('siloes') occurred through competitive short-term funding and frequent re-structuring. Reliance on the local hospital emergency department was concerning. Consumer trust, an important element in engagement, was often lacking. CONCLUSIONS: Comorbidity should be core business of both MH and AOD services by providing consistent 'no wrong door' care. Non governmental organisations (NGOs) need longer funding cycles to promote stability and retain skilled workers. Comorbidity workforce training for government and NGO staff is required. Culturally appropriate comorbidity services are urgently needed. Despite the barriers, collaboration between clinicians/workers was valued. PMID- 27406931 TI - Applying principles of the Neurosequential Model of Therapeutics across an adolescent day program and inpatient unit. AB - OBJECTIVE: The process of applying the principles of the Neurosequential Model of Therapeutics (NMT) as a practice framework in an Adolescent Day Program and Adolescent Inpatient Unit is described. CONCLUSIONS: NMT as a practice framework guided construction of a neurobiologically sensitive group therapy program whereby specific group therapies can be selected to target a young person's specific clinical needs within the context of a broader mental health treatment plan. The practice framework has been practical, logical and feasible to implement and may encourage other child and adolescent mental health services to consider the application of neuroscience-informed models such as NMT. PMID- 27406932 TI - Enhancing suicide risk assessment: a novel visual metaphor learning tool. AB - OBJECTIVE: Suicide risk assessment is variably taught and learnt by health professionals. The literature indicates that training programs of this fundamental competency need to be enhanced. To facilitate teaching and learning of this core clinical skill, we propose a novel visual metaphor in order to conceptualize suicide risk factors. The design of the proposed visual metaphor was informed by the Cognitive Load Theory to enhance deep learning of the various suicide risk factors. CONCLUSION: The visual metaphor depicting suicide risk factors can potentially improve memory and recall. It activates prior knowledge and is based on educational theory informed design principles. PMID- 27406933 TI - Nanoscale magnetism and novel electronic properties of a bilayer bismuth(111) film with vacancies and chemical doping. AB - Magnetically doped topological insulators (TIs) exhibit several exotic phenomena including the magnetoelectric effect and quantum anomalous Hall effect. However, from an experimental perspective, incorporation of spin moment into 3D TIs is still challenging. Thus, instead of 3D TIs, the 2D form of TIs may open up new opportunities to induce magnetism. Based on first principles calculations, we demonstrate a novel strategy to realize robust magnetism and exotic electronic properties in a 2D TI [bilayer Bi(111) film: abbreviated as Bi(111)]. We examine the magnetic and electronic properties of Bi(111) with defects such as bismuth monovacancies (MVs) and divacancies (DVs), and these defects decorated with 3d transition metals (TMs). It has been observed that the MV in Bi(111) can induce novel half metallicity with a net magnetic moment of 1 MUB. The origin of half metallicity and magnetism in MV/Bi(111) is further explained by the passivation of the sigma-dangling bonds near the defect site. Furthermore, in spite of the nonmagnetic nature of DVs, the TMs (V, Cr, Mn, and Fe) trapped at the 5/8/5 defect structure of DVs can not only yield a much higher spin moment than those trapped at the MVs but also display intriguing electronic properties such as metallic, semiconducting and spin gapless semiconducting properties. The predicted magnetic and electronic properties of TM/DV/Bi(111) systems are explained through density of states, spin density distribution and Bader charge analysis. PMID- 27406934 TI - Predictors of outcome after primary flexor tendon repair in zone 1, 2 and 3. AB - We retrospectively reviewed the outcomes of flexor tendon repairs in zones 1, 2 and 3 in 356 fingers in 291 patients between 2005 and 2010. The mean (standard deviation) active ranges of motion of two interphalangeal joints of the fingers were 98 degrees (40) and 114 degrees (45) at 8 weeks postoperatively and at the last follow-up (mean 7 months, range 3-98), respectively. Using the Strickland criteria, 'excellent' or 'good' function was obtained in 95 (30%) out of 322 fingers at 8 weeks and 107 (48%) out of 225 fingers at the last follow-up. A total of 48 (13%) fingers required reoperation because of rupture, adhesion, contracture or other complications. The prevalence of rupture was 4%. We carried out multiple linear regression analysis to identify the predictors of the active digital motion. The following variables were found as negative predictors: age; smoking; injury localization between subzones 1C and 2C; injury to the little finger; the extent of soft tissue damage; concomitant skeletal injury; delay to surgery; use of a 2-strand Kessler repair technique; attempted suture or preservation of the tendon sheath-pulley system; and resecting or leaving the concomitant superficial flexor tendon cuts untreated. Analysing the 8 weeks results of tendon repairs in zones 1 and 2, early active mobilization was found to be superior to Kleinert's regime. LEVEL OF EVIDENCE: III. PMID- 27406935 TI - Attempts to enhance cross-protection against porcine reproductive and respiratory syndrome viruses using chimeric viruses containing structural genes from two antigenically distinct strains. AB - Due to significant antigenic variations between field isolates of porcine reproductive and respiratory syndrome virus (PRRSV), suboptimal cross-protection between different viruses impedes the effective control of PRRS via vaccination. Our previous study showed that chimeric viruses containing mixed structural genes from two distinct strains (VR2332 and JA142) of PRRSV were highly susceptible to the viral neutralizing activity of antisera generated against both parental strains. In this study, three chimeric viruses (JAP5, JAP56 and JAP2-6) were constructed by replacing ORF5, ORFs 5 and 6, and ORFs 2-6 of VR2332 with the corresponding genes of JA142, respectively, and their ability to confer cross protection against challenge with the VR2332 and JA142 strains was evaluated in vivo. A total of 114 pigs were divided into 6 groups, and each group was intramuscularly injected with one of the 3 chimeric viruses (n=16 pigs per group), VR2332 (n=24), JA142 (n=24), or sham inoculum (n=18). At 44days post inoculation (dpi), these pigs were further divided into 15 groups (n=6 or 8 pigs per group) and intranasally challenged with VR2332, JA142, or sham inoculum. All pigs inoculated with one of the chimeric viruses prior to challenge had lower viremia levels than the challenge control pigs. Prior inoculation with JAP56 markedly decreased viremia to nearly undetectable levels in pigs challenged with either VR2332 or JA142. These results suggest that chimeric viruses harboring mixed structural genes from two distinct PRRSV strains can provide protection against both donor viruses. PMID- 27406937 TI - Rapid identification of lettuce seed germination mutants by bulked segregant analysis and whole genome sequencing. AB - Lettuce (Lactuca sativa) seeds exhibit thermoinhibition, or failure to complete germination when imbibed at warm temperatures. Chemical mutagenesis was employed to develop lettuce lines that exhibit germination thermotolerance. Two independent thermotolerant lettuce seed mutant lines, TG01 and TG10, were generated through ethyl methanesulfonate mutagenesis. Genetic and physiological analyses indicated that these two mutations were allelic and recessive. To identify the causal gene(s), we applied bulked segregant analysis by whole genome sequencing. For each mutant, bulked DNA samples of segregating thermotolerant (mutant) seeds were sequenced and analyzed for homozygous single-nucleotide polymorphisms. Two independent candidate mutations were identified at different physical positions in the zeaxanthin epoxidase gene (ABSCISIC ACID DEFICIENT 1/ZEAXANTHIN EPOXIDASE, or ABA1/ZEP) in TG01 and TG10. The mutation in TG01 caused an amino acid replacement, whereas the mutation in TG10 resulted in alternative mRNA splicing. Endogenous abscisic acid contents were reduced in both mutants, and expression of the ABA1 gene from wild-type lettuce under its own promoter fully complemented the TG01 mutant. Conventional genetic mapping confirmed that the causal mutations were located near the ZEP/ABA1 gene, but the bulked segregant whole genome sequencing approach more efficiently identified the specific gene responsible for the phenotype. PMID- 27406936 TI - Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. AB - AIM: The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. METHODS: A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine. RESULTS: Fifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV. CONCLUSION: Immunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children. CLINICAL TRIAL REGISTRATION: NCT02263703 (ClinicalTrials.gov). PMID- 27406938 TI - The reactive element effect of ceria particle dispersion on alumina growth: A model based on microstructural observations. AB - The oxidation kinetics of alumina-forming metals can be affected by adding a small amount of a reactive (normally rare earth) element oxide (RExOy) and the segregation of the reactive element (RE) ions to the growing alumina grain boundaries (GBs) has been considered as a responsible reason. However, this interpretation remains a controversial issue as to how RE ions are produced by RExOy which is thermodynamically and chemically stable in metals. The question is answered by a model that is based on transmission electron microscopy (TEM) investigation of a CeO2-dispersed nickel aluminide oxidized in air at 1100 degrees C. The CeO2 dispersion is incorporated into the alumina scale by the inward growth of inner alpha-Al2O3, where it partially dissolves producing tetravalent Ce cations which then transform to trivalent cations by trapping electrons. The trivalent cations segregate to the alpha-Al2O3 GBs and diffuse outward along first the GBs and later the twin boundaries (TBs) in the outer gamma-Al2O3 layer, being precipitated as Ce2O3 particles near surface. PMID- 27406940 TI - Resting Energy Expenditure of Children and Adolescents With Nonalcoholic Fatty Liver Disease. AB - BACKGROUND: The mainstay of treatment for pediatric nonalcoholic fatty liver disease (NAFLD) is lifestyle modification, which includes dietary changes that lead to slow but sustained weight loss or weight stabilization in growing children. Accurate estimation of energy requirements is necessary to achieve this goal. The objective of this study was to assess the accuracy of the most commonly used equations in predicting the resting energy expenditure (REE) of children with NAFLD. METHODS: This was a retrospective study performed in a single institution. The predictive accuracy of various equations was assessed by comparing their estimates against the measured REE obtained with indirect calorimetry. Accuracy was defined as an estimate within 10% of measured REE. RESULTS: Fifty-six children (70% male; 52% white and 36% Asian) with a median age of 13 years were included. The median measured REE was 1829 kcal/d. Of the equations studied, the Schofield had the smallest average bias (-32 kcal/d; confidence interval, -121 to 56). The Schofield and Molnar equations were the most accurate, providing REE estimates within 10% of measured in 59% of cases. The remaining equations had lower and variable predictive accuracy. The use of adjusted body weight in predictive equations did not improve the predictive accuracy. CONCLUSION: In a cohort of children and adolescents with NAFLD, the Schofield and Molnar equations performed best in predicting energy expenditure. However, predictive equations were often inaccurate, suggesting that clinicians should interpret their results with caution and consider using indirect calorimetry when available. PMID- 27406939 TI - Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes. AB - OBJECTIVES: The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. METHODS: We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]). RESULTS: We identified six seizure onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable. SIGNIFICANCE: Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA. PMID- 27406941 TI - Metabolites Associated With Malnutrition in the Intensive Care Unit Are Also Associated With 28-Day Mortality. AB - BACKGROUND: We hypothesized that metabolic profiles would differ in critically ill patients with malnutrition relative to those without. MATERIALS AND METHODS: We performed a prospective cohort study on 85 adult patients with systemic inflammatory response syndrome or sepsis admitted to a 20-bed medical intensive care unit (ICU) in Boston. We generated metabolomic profiles using gas and liquid chromatography and mass spectroscopy. We followed this by logistic regression and partial least squares discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis and network model construction of chemical protein target interactions to identify groups of metabolites and pathways that were differentiates in patients with and without malnutrition. RESULTS: Of the cohort, 38% were malnourished at admission to the ICU. Metabolomic profiles differed in critically ill patients with malnutrition relative to those without. Ten metabolites were significantly associated with malnutrition ( P < .05). A parsimonious model of 5 metabolites effectively differentiated patients with malnutrition (AUC = 0.76), including pyroglutamine and hypoxanthine. Using pathway enrichment analysis, we identified a critical role of glutathione and purine metabolism in predicting nutrition. Nutrition status was associated with 28-day mortality, even after adjustment for known phenotypic variables associated with ICU mortality. Importantly, 7 metabolites associated with nutrition status were also associated with 28-day mortality. CONCLUSION: Malnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism, which play principal roles in cellular redox regulation and accelerated tissue adenosine triphosphate degradation, respectively, were significantly altered with malnutrition. PMID- 27406942 TI - Severe Gut Microbiota Dysbiosis Is Associated With Poor Growth in Patients With Short Bowel Syndrome. AB - BACKGROUND: Children with short bowel syndrome (SBS) can vary significantly in their growth trajectory. Recent data have shown that children with SBS possess a unique gut microbiota signature compared with healthy controls. We hypothesized that children with SBS and poor growth would exhibit more severe gut microbiota dysbiosis compared with those with SBS who are growing adequately, despite similar intestinal anatomy. MATERIALS AND METHODS: Stool samples were collected from children with SBS (n = 8) and healthy controls (n = 3) over 3 months. Gut microbiota populations (16S ribosomal RNA sequencing and metagenomic shotgun sequencing) were compared, including a more in-depth analysis of SBS children exhibiting poor and good growth. Statistical analysis was performed using Mann Whitney, Kruskal-Wallis, and chi2 tests as appropriate. RESULTS: Children with SBS had a significant deficiency of the commensal Firmicutes order Clostridiales ( P = .025, Kruskal-Wallis) compared with healthy children. Furthermore, children with SBS and poor growth were deficient in beneficial bacteria known to produce short-chain fatty acids and had expansion of proinflammatory Enterobacteriaceae ( P = .038, Kruskal-Wallis) compared with children with SBS who were growing adequately. Using metabolic function analyses, SBS/poor growth microbiomes were deficient in genes needed for gluconeogenesis but enriched in branched and aromatic amino acid synthesis and citrate cycle pathway genes. CONCLUSIONS: Patients with SBS, particularly those with suboptimal growth, have a marked gut dysbiosis characterized by a paucity of beneficial commensal anaerobes, resulting in a deficiency of key metabolic enzymes found in the gut microbiomes of healthy children. PMID- 27406943 TI - Challenges of Quantifying FODMAPs in Enteral Nutrition Formulas: Evaluation of Artifacts and Solutions. AB - BACKGROUND: Diarrhea associated with enteral nutrition has been attributed to excessive FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) content of formulas. This study aimed to readdress their FODMAP content by measuring fermentation-specific effects after a formula load in healthy participants and by defining issues with analytical methods. METHODS: Breath hydrogen production expressed as mean area under the curve (AUC) for 12 hours after ingestion of 15 g lactulose or 500 mL of 1 of 2 formulas of seemingly different FODMAP content was evaluated in a double crossover design. Quantification of specified FODMAPs via enzymatic and liquid chromatographic assays was assessed with additional controls to investigate the influence of maltodextrin and sucrose present in the formulas, and alternative assays were applied. RESULTS: In 15 hydrogen-producing participants, AUC following both formulas was minimal (<=21 ppm/12 h) compared with 15 g lactulose ( P < .001). Elevated breath hydrogen was detectable when >2.5 g fructo-oligosaccharide was consumed. Maltodextrin showed dose-dependent interference with enzymatic measurement of fructans and coeluted with raffinose with liquid chromatography. Application of an alternative fructan assay that includes additional enzymes to hydrolyze maltodextrins indicated that fructan content was <15% of that previous reported. Galacto-oligosaccharide (GOS) content could not be estimated by chromatography due to maltodextrins. An enzymatic assay, while overestimating GOS content, showed it to be very low. CONCLUSION: FODMAPs were not detected in enteral formulas in human bioassays, and their content may be grossly overestimated mainly due to high formula concentrations of maltodextrin. Better estimates of FODMAP content in enteral formulas can be made by alternative assay approaches. PMID- 27406944 TI - Experiences of patients with intellectual disabilities and carers in GP health information exchanges: a qualitative study. AB - BACKGROUND: Accurate health information exchange (HIE) is pivotal for good quality of care. However, patients with intellectual disabilities (ID) face challenges in processing and exchanging health information around GP consultations. Knowledge of HIE barriers and facilitators, including the roles of carers, may help to improve GP care for people with ID. OBJECTIVE: To gain more insight into HIE barriers and facilitators for ID patients in GP care. METHODS: A qualitative study exploring GP consultation experiences of people with ID (n = 35), professional carers (n = 20) and relatives (n = 15). Transcripts from interviews and focus groups were analyzed using a framework analysis approach. RESULTS: Analyses resulted in four themes: (i) Recognizing patient health needs; (ii) Impaired doctor-patient communication; (iii) Carers' mediating roles during consultations; and (iv) Patients' autonomy and self-determination. Barriers related to communication skills, lack of time, continuity of carers and physicians, information alignment between relative or professional carer and the GP, and information transfer and recording within the patient network. Facilitating factors related mainly to carer interventions, personal connections with patients and GP communication with patients and carers outside the consultation. CONCLUSION: There is considerable HIE potential in patients themselves, as well as in their network, although many barriers have to be overcome to profit from this. GP practices are recommended to adjust consultations and communication practices and to facilitate deployment of the patient's network, while still considering patient autonomy. PMID- 27406945 TI - No Increased Risk of Ketoconazole Toxicity in Drug-Drug Interaction Studies. AB - In July 2013 the U.S. Food and Drug Administration (FDA) released a safety announcement regarding the use of ketoconazole and its adverse drug reactions. The FDA report advised against the use ketoconazole tablets as a first-line treatment for any fungal infections because of the risk of potentially serious drug-drug interactions and liver and adrenal gland complications. The European Medicines Agency (EMA) also proposed to limit the use of oral ketoconazole in fungal infections because of the same risk of harmful effects and interactions. In addition, the FDA also advised against the use of oral ketoconazole in drug interaction studies, in which it has been extensively used as an index inhibitor of drug metabolism. The aim of this investigation was to evaluate the risks of ketoconazole-induced hepatotoxicity described by the FDA and EMA in published drug interaction studies with ketoconazole and compare these data with the toxicity reported for ketoconazole when used as antifungal treatment. In the drug interaction studies (2355 participants; healthy volunteers and patients; median treatment duration, 6 days), only 40 participants were reported to have increased liver transaminase activity (1.7%), and no deaths were reported or associated with ketoconazole. In studies investigating ketoconazole treatment, patients were treated for 276 days (median), and 5.6% of patients had elevated liver enzyme activity. Because of the short treatment period in drug interaction studies the risk of drug-induced hepatic injury is considered very low. As such, we recommend that ketoconazole remain a safe CYP3A index inhibitor for use in drug interaction studies with healthy volunteers. PMID- 27406946 TI - An internal electron reservoir enhances catalytic CO2 reduction by a semisynthetic enzyme. AB - The development of an artificial metalloenzyme for CO2 reduction is described. The small-molecule catalyst [Ni(II)(cyclam)](2+) has been incorporated within azurin. Selectivity for CO generation over H(+) reduction is enhanced within the protein environment, while the azurin active site metal impacts the electrochemical overpotential and photocatalytic activity. The enhanced catalysis observed for copper azurin suggests an important role for intramolecular electron transfer, analogous to native CO2 reducing enzymes. PMID- 27406947 TI - Thirty-five years of CD4 T-cell counting in HIV infection: From flow cytometry in the lab to point-of-care testing in the field. AB - CD4 T-cell counting was introduced in clinical laboratories shortly after the discovery of the human immune deficiency virus (HIV) in the early eighties. In western clinical laboratories, improvements in the CD4 T-cell counting methods were mainly driven by progress in the field of flow cytometry and immunology. In contrast, the development of dedicated CD4 T-cell counting technologies were needs driven. When antiretroviral treatment (ART) was made available on a large scale by international Acquired Immune Deficiency Syndrome (AIDS) relief programs to HIV+ patients living in low income countries in 2003, there was a distinct need for simplified and affordable CD4 T-cell counting technologies. The first decade of 2000, several compact flow cytometers appeared on the market, mainly to the benefit of low income countries with limited resources. More recently, however, portable point-of-care (POC) CD4 T-cell counting devices have been developed especially to improve access to affordable monitoring of HIV+ patients in low income countries. The accuracy of these POC instruments is not yet very well documented as many are still under development and clinical validation but preliminary evidence is encouraging. The new HIV treatment guidelines released by the World Health Organization in 2016 give CD4 T-cell counting a less central role in the management of HIV infection. It is, therefore, to be expected that CD4 T-cell counting will be phased out as a tool to assess eligibility of HIV+ patients for ART in the future. However, CD4 T-cell counting will remain a valuable tool for directing treatment against opportunistic infections. (c) 2016 International Clinical Cytometry Society. PMID- 27406948 TI - Clinical decision-making in azoospermic men: in search of the ideal prediction model. PMID- 27406949 TI - Prediction model for live birth in ICSI using testicular extracted sperm. AB - STUDY QUESTION: Which parameters have a predictive value for live birth in couples undergoing ICSI after successful testicular sperm extraction (TESE-ICSI)? SUMMARY ANSWER: Female age, a first or subsequent started TESE-ICSI cycle, male LH, male testosterone, motility of the spermatozoa during the ICSI procedure and the initial male diagnosis before performing TESE were identified as relevant and independent parameters for live birth after TESE-ICSI. WHAT IS KNOWN ALREADY: In reproductive medicine prediction models are used frequently to predict treatment success, but no prediction model currently exists for live birth after TESE-ICSI. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study between 2007 and 2015 in two academic hospitals including 1559 TESE-ICSI cycles. The prediction model was developed using data from one centre and validation was performed with data from the second centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included couples undergoing ICSI treatment with surgically retrieved sperm from the testis for the first time. In the development set we included 526 couples undergoing 1006 TESE-ICSI cycles. In the validation set we included 289 couples undergoing 553 TESE-ICSI cycles. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.2 for entry). The external validation was based on discrimination and calibration. MAIN RESULTS AND THE ROLE OF CHANCE: We included 224 couples (22.3%) with a live birth in the development set. The occurrence of a live birth was associated with lower female age, first TESE-ICSI cycle, lower male LH, higher male testosterone, the use of motile spermatozoa for ICSI and having obstructive azoospermia as an initial suspected diagnosis. The area under the receiver operating characteristic (ROC) curve was 0.62. From validation data, the model had moderate discriminative capacity (c-statistic 0.67, 95% confidence interval: 0.62-0.72) but calibrated well, with a range from 0.06 to 0.56 in calculated probabilities. LIMITATIONS, REASONS FOR CAUTION: We had a lack of data about the motility of spermatozoa during TESE, therefore, we used motility of the spermatozoa used for ICSI after freeze-thawing, information which is only available during treatment. We had to exclude data on paternal BMI in the model because too many missing values in the validation data hindered testing. We did not include a histologic diagnosis, which would have made our data set less heterogeneous and, finally, our model may not be applicable in centres which have a different policy for the indication for performing sperm extraction. The prognostic value of the model is limited because of a low 'area under the curve'. WIDER IMPLICATIONS OF THE FINDINGS: This model enables the differentiation between couples with a low or high chance to reach a live birth using TESE-ICSI. As such it can aid in the counselling of patients and in clinical decision making. STUDY FUNDING/COMPETING INTERESTS: This study was partly supported by an unconditional grant from Merck Serono (to D.D.M.B. and K.F.) and by the Department of Obstetrics and Gynaecology of Radboud University Medical Center, Nijmegen, The Netherlands, the Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands, and the Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands. Merck Serono had no influence in concept, design, nor elaboration of this study. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 27406951 TI - Anion induced structural transformation in silver-(3,6-dimethoxy-1,2,4,5 tetrazine) coordination polymers under mechanochemical conditions. AB - Mechanochemical reactions of 3,6-dimethoxy-s-tetrazine (dmotz) with AgCF3SO3 and AgClO4 afforded the 1D linear polymer [Ag(dmotz)(CF3SO3)]n (1) and the 2D grid polymer {[Ag(dmotz)2](ClO4)}n (2), respectively. Mechanochemical processes convert 1 to 2 in the presence of an equivalent of [ClO4](-) and dmotz; even on using excess [CF3SO3](-), conversion from 2 to 1 was not observed. PMID- 27406950 TI - Prediction model for obtaining spermatozoa with testicular sperm extraction in men with non-obstructive azoospermia. AB - STUDY QUESTION: Can an externally validated model, based on biological variables, be developed to predict successful sperm retrieval with testicular sperm extraction (TESE) in men with non-obstructive azoospermia (NOA) using a large nationwide cohort? SUMMARY ANSWER: Our prediction model including six variables was able to make a good distinction between men with a good chance and men with a poor chance of obtaining spermatozoa with TESE. WHAT IS KNOWN ALREADY: Using ICSI in combination with TESE even men suffering from NOA are able to father their own biological child. Only in approximately half of the patients with NOA can testicular sperm be retrieved successfully. The few models that have been developed to predict the chance of obtaining spermatozoa with TESE were based on small datasets and none of them have been validated externally. STUDY DESIGN, SIZE, DURATION: We performed a retrospective nationwide cohort study. Data from 1371 TESE procedures were collected between June 2007 and June 2015 in the two fertility centres. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men with NOA undergoing their first TESE procedure as part of a fertility treatment were included. The primary end-point was the presence of one or more spermatozoa (regardless of their motility) in the testicular biopsies.We constructed a model for the prediction of successful sperm retrieval, using univariable and multivariable binary logistic regression analysis and the dataset from one centre. This model was then validated using the dataset from the other centre. The area under the receiver-operating characteristic curve (AUC) was calculated and model calibration was assessed. MAIN RESULTS AND THE ROLE OF CHANCE: There were 599 (43.7%) successful sperm retrievals after a first TESE procedure. The prediction model, built after multivariable logistic regression analysis, demonstrated that higher male age, higher levels of serum testosterone and lower levels of FSH and LH were predictive for successful sperm retrieval. Diagnosis of idiopathic NOA and the presence of an azoospermia factor c gene deletion were predictive for unsuccessful sperm retrieval. The AUC was 0.69 (95% confidence interval (CI): 0.66-0.72). The difference between the mean observed chance and the mean predicted chance was <2.0% in all groups, indicating good calibration. In validation, the model had moderate discriminative capacity (AUC 0.65, 95% CI: 0.62-0.72) and moderate calibration: the predicted probability never differed by more than 9.2% of the mean observed probability. LIMITATIONS, REASONS FOR CAUTION: The percentage of men with Klinefelter syndrome among men diagnosed with NOA is expected to be higher than in our study population, which is a potential selection bias. The ability of the sperm retrieved to fertilize an oocyte and produce a live birth was not tested. WIDER IMPLICATIONS OF THE FINDINGS: This model can help in clinical decision-making in men with NOA by reliably predicting the chance of obtaining spermatozoa with TESE. STUDY FUNDING/COMPETING INTEREST: This study was partly supported by an unconditional grant from Merck Serono (to D.D.M.B. and K.F.) and by the Department of Obstetrics and Gynaecology of Radboud University Medical Center, Nijmegen, The Netherlands, the Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands, and the Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands. Merck Serono had no influence in concept, design nor elaboration of this study. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 27406952 TI - Sweetened beverage consumption is a risk factor for depressive symptoms among adolescents living in Boston, Massachusetts, USA. AB - OBJECTIVE: To investigate the relationship between sweetened beverage consumption and depressive symptoms among adolescents. DESIGN: In a cross-sectional study, adolescents were asked how often they drank soda and fruit drinks in the past 7 d. Depressive symptoms were measured using a brief adapted version of the Modified Depression Scale. Summation scores were standardized using the Z transformation. We used multilevel multiple linear regression models to estimate the association between soda and fruit drink consumption and depressive symptoms. SETTING: The 2008 Boston Youth Survey. SUBJECTS: Adolescents (n 1878), high school students in grades 9-12 of Boston public schools, Massachusetts, USA. RESULTS: Compared with those who never drank soda in the past 7 d, those who consumed soda 2-6 times/week (beta=0.18; 95 % CI 0.04, 0.32) or >=1 times/d (beta=0.29; 95 % CI 0.13, 0.45) had higher depressive symptoms. Similarly, those who consumed fruit drinks 2-6 times/week (beta=0.14; 95 % CI 0.00, 0.28) and those who consumed >=1 times/d (beta=0.22; 95 % CI 0.04, 0.40) had higher depressive symptoms. CONCLUSIONS: Frequent consumption of both soda and fruit drinks is associated with greater depressive symptoms among adolescents. PMID- 27406954 TI - Polymeric nanocapsules with up-converting nanocrystals cargo make ideal fluorescent bioprobes. AB - An innovative approach for up-converting nanoparticles adaptation for bio-related and theranostic applications is presented. We have successfully encapsulated multiple, ~8 nm in size NaYF4 nanoparticles inside the polymeric nanocarriers with average size of ~150 nm. The initial coating of nanoparticles surfaces was preserved due to the hydrophobic environment inside the nanocapsules, and thus no single nanoparticle surface functionalization was necessary. The selection of biodegradable and sugar-based polyelectrolyte shells ensured biocompatibility of the nanostructures, while the choice of Tm(3+) and Yb(3+) NaYF4 nanoparticles co doping allowed for near-infrared to near-infrared bioimaging of healthy and cancerous cell lines. The protective role of organic shell resulted in not only preserved high up-converted emission intensity and long luminescence lifetimes, without quenching from water environment, but also ensured low cytotoxicity and high cellular uptake of the engineered nanocapsules. The multifunctionality of the proposed nanocarriers is a consequence of both the organic exterior part that is accessible for conjugation with biologically important molecules, and the hydrophobic interior, which in future application may be used as a container for co-encapsulation of inorganic nanoparticles and anticancer drug cargo. PMID- 27406955 TI - Biobridge concept in stem cell therapy for ischemic stroke. AB - Stroke causes a significant social and economic burden to the society. Despite advancement in awareness and prevention of stroke, there are still limited treatment options for stroke patients. One of the emerging experimental therapies for stroke is stem cell transplantation. The conventional belief of stem cell mechanisms is that the protective effects are produced by either cell replacement or releasing trophic factors. While the exact mechanisms of action of stem cells are not completely understood, recent evidence demonstrates another possible mechanism of stem cells. This new approach emphasizes on the formation of a biobridge between the damage area and the endogenous neurogenic niches of the brain. The transplanted cells can form a pathway which promotes the proliferation and migration of the endogenous stem cells. This paper discusses the use of stem cell transplantation for stroke with an emphasis on the new biobridge concept. Also discussed are the current challenges faced before this approach can advance to the clinical setting. PMID- 27406953 TI - An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy. AB - Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p=0.043 for the WHO grade II gliomas, p=0.002 for the grade III gliomas and p=0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme. PMID- 27406956 TI - Computer aided detection and classification of acute lymphoblastic leukemia cell subtypes based on microscopic image analysis. AB - Acute lymphoblastic leukemia (ALL) is a cancer that starts from the early version of white blood cells called lymphocytes in the bone marrow. It can spread to different parts of the body rapidly and if not treated, would probably be deadly within a couple of months. Leukemia cells are categorized into three types of L1, L2, and L3. The cancer is detected through screening of blood and bone marrow smears by pathologists. But manual examination of blood samples is a time consuming and boring procedure as well as limited by human error risks. So to overcome these limitations a computer-aided detection system, capable of discriminating cancer from noncancer cases and identifying the cancerous cell subtypes, seems to be necessary. In this article an automatic detection method is proposed; first cell nucleus is segmented by fuzzy c-means clustering algorithm. Then a rich set of features including geometric, first- and second-order statistical features are obtained from the nucleus. A principal component analysis is used to reduce feature matrix dimensionality. Finally, an ensemble of SVM classifiers with different kernels and parameters is applied to classify cells into four groups, that is noncancerous, L1, L2, and L3. Results show that the proposed method can be used as an assistive diagnostic tool in laboratories. PMID- 27406957 TI - Ocular findings in coal miners diagnosed with pneumoconiosis. PMID- 27406959 TI - Molecular cloning, refined chromosomal mapping and structural analysis of the human gene encoding aldehyde oxidase (AOX1), a candidate for the ALS2 gene. AB - Aldehyde oxidase (AOX) is a member of the xanthine oxidase (XO) family of molybdenum hydroxylase, iron-sulfur flavoproteins and is involved in the metabolism of a wide range of native and xenobiotic compounds. The potentially toxic reduced oxygen intermediates (ROI), hydrogen peroxide (H2O2) and superoxide anion (O2(.-)), are generated when reduced AOX becomes oxidized by molecular oxygen, raising the possibility for involvement of AOX in pathophysiology. Indeed, ROI generation by AOX has been directly implicated in hepatic ethanol toxicity. A cDNA encoding human AOX has been cloned, sequenced, and identified as AOX1. AOX1 was proposed as a candidate for an autosomal recessive form of amyotrophic lateral sclerosis (ALS2) because a YAC carrying AOX1 was mapped to the ALS2 locus and was expressed in microglial cells of the spinal cord. As a source of H2O2, AOX could mediate motor neuron degeneration. To provide a basis for further analysis of AOX1 in pathophysiology, and to examine the relationship of the human AOX1 gene to the gene for human xanthine dehydrogenase (XDH), we have studied the chromosomal locus encoding AOX1 in humans. In the present communication, we have analyzed P1 artificial chromosomes containing AOX1. Our refined chromosomal mapping by FISH locates AOX1 very centromere proximal in the 2q33 region at 2q32.3-2q33.1. We present the first complete structural map of an AOX gene and provide direct evidence that human XDH and AOX1 are related by a gene duplication event. In addition, 1500 bp of upstream DNA containing the putative AOX1 promoter were sequenced and expressed. In contrast to the amino acid coding regions, AOX1 and XDH promoter sequences exhibit marked divergence that reflects the differential activation of these closely related genes. Evidence is presented that AOX may be polygenic in humans as it is in plants, Dipterans, and mice. PMID- 27406958 TI - A Synthetic Oxygen Atom Transfer Photocycle from a Diruthenium Oxyanion Complex. AB - Three new diruthenium oxyanion complexes have been prepared, crystallographically characterized, and screened for their potential to photochemically unmask a reactive Ru-Ru?O intermediate. The most promising candidate, Ru2(chp)4ONO2 (4, chp = 6-chloro-2-hydroxypyridinate), displays a set of signals centered around m/z = 733 amu in its MALDI-TOF mass spectrum, consistent with the formation of the [Ru2(chp)4O](+) ([6](+)) ion. These signals shift to 735 amu in 4*, which contains an (18)O-labeled nitrate. EPR spectroscopy and headspace GC-MS analysis indicate that NO2(*) is released upon photolysis of 4, also consistent with the formation of 6. Photolysis of 4 in CH2Cl2 at room temperature in the presence of excess PPh3 yields OPPh3 in 173% yield; control experiments implicate 6, NO2(*), and free NO3(-) as the active oxidants. Notably, Ru2(chp)4Cl (3) is recovered after photolysis. Since 3 is the direct precursor to 4, the results described herein constitute the first example of a synthetic cycle for oxygen atom transfer that makes use of light to generate a putative metal oxo intermediate. PMID- 27406960 TI - Combined effect of 3-aminobenzamide and N-acetylcysteine on HIV replication in chronically infected U937 cells. AB - The existence of a close relationship between apoptosis associated with oxidative stress and the increase of viral progeny in chronically HIV-infected cells has been previously reported. The possibility of modulating both phenomena by using an antioxidant such as N-acetylcysteine (NAC) has also been demonstrated. The present investigation was designed to study the role of the nuclear enzyme poly (ADP-ribose)-polymerase (PARP) when HIV- infected cells are treated with tumour necrosis factor alpha (TNFalpha), a cytokine capable of inducing both apoptosis and intracellular oxygen free radical production. PARP overexpression may result in a rapid drop of intracellular NAD(+) and ATP concentration, thus contributing to cellular redox imbalance. We have used the specific PARP inhibitor 3- aminobenzamide (3-ABA), alone or in a combination with NAC. 3-ABA was only partially capable of inhibiting viral replication and apoptosis induced by TNFalpha. In contrast, the combination of NAC and 3-ABA led to an inhibition of apoptosis as well as to a marked decrease in viral particle production, with a parallel replenishment of intracellular reduced glutathione content. The results reported here confirm the potential role of antioxidant drug treatment in specific phases of HIV infection. PMID- 27406961 TI - Ebselen protects Chinese hamster ovary cells from radiation-induced apoptosis. AB - Radiation-induced apoptosis in chinese hamster ovary (CHO) cell lines is characterized by endonucleolytic cleavage of cellular DNA and changes of cell morphology within hours after radiation exposure. We investigated the capacity of ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], a seleno-organic compound with selenium-dependent glutathione peroxidase (GPx) activity, to protect cells from radiation-induced apoptosis. This phenomenon was studied by the quantitation of apoptotic cells and DNA gel electrophoresis after 6 Gy X-ray exposure. We also measured the activity of GPx and membrane lipid peroxidation. It was observed that 20 uM ebselen efficiently blocked apoptotic cell formation and DNA fragmentation 48 h post irradiation. Furthermore the data demonstrated that lipid peroxides increased significantly in irradiated cells and ebselen inhibited this process by elevating the cellular GPx activity. The results presented here indicate the requirement of free radicals for radiation-induced apoptosis and ultimately may yield insight necessary for designing protocols to modulate the process of radiation-induced apoptosis with antioxidant agents that scavenge radiation-induced free radicals. PMID- 27406962 TI - Pharmacologic interception of heme: a potential therapeutic strategy for the treatment of beta thalassemia? AB - Pro-oxidant effects of hemoglobin-derived heme and iron contribute to the progressive damage observed in beta thalassemic and sickle (HbS) red blood cells. Agents that prevent heme/iron release and inhibit their redox activity might diminish such injury. Consequently, the inhibitory effects of chloroquine (CQ), a heme-binding antimalarial drug, and a novel dichloroquine compound (CQ-D2) on iron release and lipid peroxidation were investigated. In contrast to normal hemoglobin, significant amounts of iron were released from both purified hemin and alpha-hemoglobin chains during incubations with exogenous reduced glutathione (GSH) and/or H2O2. Addition of either CQ or CQ-D2 effectively inhibited GSH- and GSH/H2O2-mediated iron release from hemin (P<0.001). During prolonged incubations (6 h), both CQ and CQ-D2 significantly decreased the release of heme-free iron from both purified hemoglobin and alpha-hemoglobin chains. Interestingly, CQ and CQ-D2 differentially affected the redox availability of the heme-bound iron. The CQ: heme complex significantly enhanced membrane lipid peroxidation whereas CQ-D2 dramatically (P<0.001) inhibited heme-dependent peroxidation to almost baseline levels. In summary, CQ-derivatives which render heme redox inert and prevent the release of free iron from heme might be beneficial in the treatment of certain hemoglobinopathies and, perhaps, other pathologies promoted by delocalized heme/iron. PMID- 27406963 TI - Cigarette smoke induced oxidation of human plasma proteins, lipids, and antioxidants; selective protection by the biothiols dihydrolipoic acid and glutathione. AB - Exposure of human plasma to gas-phase cigarette smoke (CS) causes loss of human plasma antioxidants, protein modification (Frei et al, Biochem J, 1991 277:133 138; Reznick et al, Biochem J, 1992 286: 607-611) and a minimal amount of lipid oxidation. Ascorbic acid was found to prevent CS-induced lipid peroxidation and glutathione (GSH) partially protected against protein modification, as determined by loss of protein -SH groups and by increases in carbonyl content as a measure of protein oxidation. In the present study we demonstrate that dihydrolipoic acid (0.25-1.0 mM) decreases CS-induced protein carbonyls, alpha-tocopherol loss, and lipid hydroperoxide formation in plasma. In contrast GSH (1 mM) failed to influence CS-induced loss of alpha-tocopherol, and was 50% as effective as dihydrolipoate in protecting against CS-induced protein carbonyl formation. On the other hand, lipoic acid (oxidized form of dihydrolipoic acid) and oxidized glutathione (GSSG) had minimal effect in protecting against the CS-induced protein modifications. These findings demonstrate that low molecular weight thiols are capable of modifying the effect of gas-phase CS on biological fluids. Dihydrolipoate appears to be particularly useful in that it was shown to conserve ascorbic acid and alpha-tocopherol, i.e. supporting the antioxidant network concept in protection against protein and lipid oxidation. PMID- 27406964 TI - The effect of histidine modification on copper-dependent lipid peroxidation in human low-density lipoprotein. AB - Lipid peroxidation and subsequent oxidative modification of low-density lipoprotein (LDL) have been implicated as causal events in atherosclerosis. Cu(2+) may play an important role in LDL oxidation by binding to histidine residues of apolipoprotein B-100 (apo B) and initiating and propagating lipid peroxidation. To investigate the role of histidine residues, we used diethylpyrocarbonate (DEPC), a lipid-soluble histidine-specific modifying reagent. When LDL (0.1 mg protein/ml, or 0.2 uM) was incubated with DEPC (1 mM), at least 76 +/- 7% of the histidine residues in apo B were modified. Treatment of LDL with DEPC led to an increase in the rate of Cu(2+)-induced initiation of lipid peroxidation (Ri), but a significant decrease in the rate of propagation. These changes resulted in an overall increased resistance of LDL to oxidation, with a significantly increased lag phase preceding the propagation phase of lipid peroxidation. In contrast to DEPC, ascorbate completely prevented the initiation of LDL oxidation (Ri = 0). Our data indicate that there are two types of copper/histidine binding sites on apo B: those facing the lipid core of the LDL particle, which mediate the propagation of lipid peroxidation and are modified by DEPC; and those found on the surface of the LDL particle exposed to the aqueous environment, which are responsible for mediating the initiation of lipid peroxidation and are modifiable by ascorbate in the presence of Cu(2+). PMID- 27406965 TI - Oxidative damage induced by a novel porphyrin on rat brain mitochondria and its possible implications in therapy. AB - Free radical-induced oxidative damage is involved in several pathological disorders. On the other hand, selective induction of peroxidation in diseased tissue is a promising approach to the treatment of cancer by photodynamic therapy. In this study we have used rat brain mitochondria as a model to evaluate the ability of a new water soluble porphyrin, 5,10,15,20-tetrakis[4 (carboxymethyleneoxy)phenyl]porphyrin (T4CPP), to induce peroxidative damage during photosensitization. Peroxidation in mitochondria, one of the crucial targets of the photodynamic effect, was assessed from the formation of thiobarbituric acid reactive substances and lipid hydroperoxides. The effect on mitochondrial function was estimated from the loss of a mitochondrial marker enzyme, succinate dehydrogenase (SDH). The photodamage was observed to be time- and concentration-dependent of T4CPP. Inhibition studies suggested involvement of singlet oxygen ((1)O2) and, to a lesser extent, of hydroxyl (OH), peroxyl (ROO( )) and superoxide radicals (O2(-)) in the photodamage. The addition of gamma linolenic acid (a promoter of lipid peroxidation) to the system led to an enhancement of the T4CPP-induced peroxidative damage. Thus, our study indicated that the combination of gamma-linolenic acid and T4CPP could enhance the photodynamic effect and has potential applications in photodynamic therapy. PMID- 27406967 TI - SFRR-ASIA/COSTAM/UNESCO-MCBN Workshop: Biological Oxidants & Antioxidants: Molecular Mechanisms and Health Effects. PMID- 27406966 TI - Inhibition of naphthohydroquinone autoxidation by DT-diaphorase (NAD(P)H:[quinone acceptor] oxidoreductase). AB - It has been reported that little redox cycling occurs during the reduction of 2 methyl-1,4-naphthoquinone by DT-diaphorase, suggesting that the reduction product, 2-methyl-1,4-naphthohydroquinone, does not readily undergo autoxidation. In the present study, however, it has been shown that DT-diaphorase, by virtue of its ability to re-reduce the naphthoquinone formed in the oxidation reaction, decreases the rate of autoxidation of 2-methyl-1,4- naphthohydroquinone. Therefore, the low rate of redox cycling observed does not reflect an intrinsic stability of the hydroquinone but inhibition of its autoxidation by the enzyme. Redox cycling of 2,3-dimethyl-, 2,3-dimethoxy- and 2-methoxy-1,4-naphthoquinone, and the autoxidation of their respective hydroquinones, were similarly inhibited by diaphorase. The concentration of the enzyme required for inhibition varied widely among the different compounds, and this was related to the autoxidation rate of the hydroquinone and the rate at which the corresponding quinone was reduced by diaphorase. The behaviour of 2-hydroxy-1,4-naphthoquinone was exceptional in that the rate of redox cycling increased with increasing levels of diaphorase and no inhibition of the autoxidation of the hydroquinone derived from this substance could be demonstrated, even at very high enzyme concentrations. The results of the present experiments indicate that the relative stability of naphthohydroquinones cannot be judged on the basis of studies involving reduction of the quinone by DT-diaphorase and suggest that current concepts on the role of this enzyme in the detoxification of quinones may need revision. PMID- 27406968 TI - Prospective Validation of the NIAID/FAAN Criteria for Emergency Department Diagnosis of Anaphylaxis. AB - BACKGROUND: Anaphylaxis diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis. These criteria were 97% sensitive and 82% specific when retrospectively validated. OBJECTIVE: To prospectively evaluate the diagnostic accuracy of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for diagnosis of anaphylaxis in the emergency department (ED). METHODS: We conducted a prospective observational study of patients seen in our institution's ED from April 2010 to March 2013. Patients seeking care for an allergic reaction and possible anaphylaxis were enrolled. Patients and providers completed questionnaires regarding onset, trigger, and signs and symptoms. Records were reviewed independently and blindly by 2 board-certified allergist immunologists, and their final diagnosis (anaphylaxis vs no anaphylaxis) was used as the reference standard. Two-by-two tables were built, and test characteristics were calculated. RESULTS: Among the 174 enrolled patients, 91 (52%) met the NIAID/FAAN criteria for anaphylaxis. The allergist-immunologists diagnosed 61 cases of anaphylaxis (35%), of which 58 (95%) also satisfied the NIAID/FAAN criteria. The interrater agreement between allergist-immunologists was substantial (kappa = 0.7). Test characteristics (95% CIs) of the NIAID/FAAN criteria were as follows: sensitivity, 95.1% (85.4%-98.7%); specificity, 70.8% (61.4%-78.8%); positive predictive value, 63.7% (52.9%-73.4%); negative predictive value, 96.4% (89.1%-99.1%); positive likelihood ratio, 3.26; and negative likelihood ratio, 0.07. CONCLUSIONS: Prospectively, the NIAID/FAAN criteria continued to be highly sensitive (95%) but had lower specificity (71%) than on retrospective assessment. These criteria are likely to be useful for the diagnosis of anaphylaxis in the ED. PMID- 27406969 TI - Skin testing, graded challenge, and desensitization to von Willebrand factor (VWF) products in type III von Willebrand disease (VWD). PMID- 27406970 TI - Updated epinephrine autoinjector labeling. PMID- 27406971 TI - Preparation and characterization of ZnO-PMMA resin nanocomposites for denture bases. AB - PURPOSE: The aim of the paper was to investigate the antifungal activity of zinc oxide nanoparticles (ZnONPs) against Candida albicans. Some attempts have been made to find out the best way to introduce ZnONPs into polymethyl methacrylate (PMMA) resin material and to determine some parameters of a newly formed composite. MATERIAL AND METHODS: Zinc oxide nanoparticles were manufactured and their basic physical parameters were determined (average particle size, density, specific surface area). Minimal inhibitory concentration (MIC) of ZnONPs was determined for the Candida albicans standard strain. The average size of ZnO conglomerates in the monomer solution of PMMA resin was measured using a dynamic light scattering instrument. PMMA resin samples with incorporated ZnONPs were produced. The morphology of nanopowder and the newly formed composite was examined under a scanning electron microscope (SEM). In addition, the roughness parameter of PMMA resin material was investigated before and after ZnONPs modification. RESULTS: Nanopowder with the average particle size of 30 nm, density of 5.24 g/cm3 and surface area of 39 m2/g was obtained. MIC was determined at the level of 0.75 mg/mL. The average size of ZnO conglomerates in the monomer solution of acrylic resin dropped by 11 times after ultrasound activation. SEM examination of a newly formed composite showed a successful introduction of ZnONPs confirmed by the energy dispersive X-ray spectroscopy (EDS) analysis. There were no statistically significant differences in the biomaterial roughness before and after the modification of ZnONPs. CONCLUSION: Zinc oxide nanoparticles were successfully incorporated into acrylic resin used for the production of denture bases. The presence of nanoparticles with sizes below 100 nm was confirmed. Nevertheless a newly created composite needs to be further investigated to improve its homogeneity, and to check its microbiological properties, strength and biocompatibility prior to its possible clinical use. PMID- 27406974 TI - Recent progress in hollow sphere-based electrodes for high-performance supercapacitors. AB - Hollow spheres have drawn much attention in the area of energy storage and conversion, especially in high-performance supercapacitors owing to their well defined morphologies, uniform size, low density and large surface area. And quite some significant breakthroughs have been made in advanced supercapacitor electrode materials with hollow sphere structures. In this review, we summarize and discuss the synthesis and application of hollow spheres with controllable structure and morphology as electrode materials for supercapacitors. First, we briefly introduce the fabrication strategies of hollow spheres for electrode materials. Then, we discuss in detail the recent advances in various hollow sphere-based electrode materials for supercapacitors, including single-shelled, yolk-shelled, urchin-like, double-shelled, multi-shelled, and mesoporous hollow structure-based symmetric and asymmetric supercapacitor devices. We conclude this review with some perspectives on the future research and development of the hollow sphere-based electrode materials. PMID- 27406972 TI - An investigation of BMP-7 mediated alterations to BMP signalling components in human tenocyte-like cells. AB - The incidence of tendon re-tears post-surgery is an ever present complication. It is suggested that the application of biological factors, such as bone morphogenetic protein 7 (BMP-7), can reduce complication rates by promoting tenogenic characteristics in in vitro studies. However, there remains a dearth of information in regards to the mechanisms of BMP-7 signalling in tenocytes. Using primary human tenocyte-like cells (hTLCs) from the supraspinatus tendon the BMP-7 signalling pathway was investigated: induction of the BMP associated Smad pathway and non-Smad pathways (AKT, p38, ERK1/2 and JNK); alterations in gene expression of BMP-7 associated receptors, Smad pathway components, Smad target gene (ID1) and tenogenic marker scleraxis. BMP-7 increases the expression of specific BMP associated receptors, BMPR-Ib and BMPR-II, and Smad8. Additionally, BMP-7 activates significantly Smad1/5/8 and slightly p38 pathways as indicated by an increase in phosphorylation and proven by inhibition experiments, where p-ERK1/2 and p-JNK pathways remain mainly unresponsive. Furthermore, BMP-7 increases the expression of the Smad target gene ID1, and the tendon specific transcription factor scleraxis. The study shows that tenocyte-like cells undergo primarily Smad8 and p38 signalling after BMP-7 stimulation. The up-regulation of tendon related marker genes and matrix proteins such as Smad8/9, scleraxis and collagen I might lead to positive effects of BMP-7 treatment for rotator cuff repair, without significant induction of osteogenic and chondrogenic markers. PMID- 27406973 TI - Delivering tailored surgery to older cancer patients: Preoperative geriatric assessment domains and screening tools - A systematic review of systematic reviews. AB - The onco-geriatric population is increasing and thus more and more elderly will require surgery; an important treatment modality for many cancer types. This population's heterogeneity demands preoperative risk stratification, which has led to the introduction of Geriatric Assessment (GA) and associated screening tools in surgical oncology. Many reviews have investigated the use of GA in onco geriatric patients. Discrepancies in outcomes between studies currently hamper the implementation of a preoperative GA in clinical practice. A systematic review of systematic reviews was performed in order to investigate assessment tools of the most commonly included GA domains and their predictive ability regarding the adverse postoperative outcomes. All domains - except polypharmacy - were, to a varying degree, associated with different adverse postoperative outcomes. Functional status, comorbidity and frailty were assessed most frequently and were most often significant. The association between domain impairments and adverse postoperative outcomes appeared to be greatly influenced by the study population characteristics and selection bias, as well as the type of assessment tool used due to possible ceiling effects and its sensitivity to detect domain impairments. Frailty seems to be the most important predictor, which underpins the importance of an integrated approach. As it is unlikely that one universal GA will fit all, feasibility, based on the time, expertise, and resources available in daily clinical practice as well as the patient population to hand, should be taken into consideration, when tailoring the 'optimal GA'. PMID- 27406975 TI - The preventive effects of lifestyle intervention on the occurrence of diabetes mellitus and acute myocardial infarction in metabolic syndrome. AB - OBJECTIVES: Metabolic syndrome (MS), as a precursor of diabetes mellitus (DM) and cardiovascular disease, is increasing steadily worldwide. We examined the preventive effects of lifestyle intervention on the occurrence of DM and acute myocardial infarction (AMI) in MS. STUDY DESIGN: Observational study on disease occurrence after lifestyle intervention. METHODS: The lifestyle intervention was administered to subjects with MS participating in a metropolitan lifestyle intervention program for 1 year. The same numbers of non-participating age- and sex-matched subjects with MS were randomly extracted from national health examination data. After intervention or examination, new occurrences of hypertension, DM, and AMI were identified through the national health insurance claims data during 1 year. For DM and AMI, multivariate logistic regression analysis for the factors affecting each disease was performed. RESULTS: In the intervention group and the control group (14,918 in each group), the occurrence of hypertension was 555 (6.07%) and 751 (8.33%), the occurrence of DM was 324 (2.55%) and 488 (3.89%), the occurrence of dyslipidemia was 321 (2.59%) and 373 (2.72%), and the occurrence of AMI was 13 (0.09%) and 26 (0.17%), respectively. In multivariate logistic regression analysis, adjusted odds ratios for intervention were 0.752 (95% confidence interval [CI]: 0.644-0.879) and 0.499 (95% CI: 0.251-0.992) for DM and AMI, respectively, indicating that lifestyle intervention has a preventive effect. CONCLUSIONS: Lifestyle intervention in MS has preventive effects on the occurrence of DM and AMI, and long-term follow-up is needed to evaluate these preventive effects in more detail. PMID- 27406976 TI - Bespoke contrast-matched diblock copolymer nanoparticles enable the rational design of highly transparent Pickering double emulsions. AB - We report the preparation of highly transparent oil-in-water Pickering emulsions using contrast-matched organic nanoparticles. This is achieved via addition of judicious amounts of either sucrose or glycerol to an aqueous dispersion of poly(glycerol monomethacrylate)56-poly(2,2,2-trifluoroethyl methacrylate)500 [PGMA-PTFEMA] diblock copolymer nanoparticles prior to high shear homogenization with an equal volume of n-dodecane. The resulting Pickering emulsions comprise polydisperse n-dodecane droplets of 20-100 MUm diameter and exhibit up to 96% transmittance across the visible spectrum. In contrast, control experiments using non-contrast-matched poly(glycerol monomethacrylate)56-poly(benzyl methacrylate)300 [PGMA56-PBzMA300] diblock copolymer nanoparticles as a Pickering emulsifier only produced conventional highly turbid emulsions. Thus contrast matching of the two immiscible phases is a necessary but not sufficient condition for the preparation of highly transparent Pickering emulsions: it is essential to use isorefractive nanoparticles in order to minimize light scattering. Furthermore, highly transparent oil-in-water-in-oil Pickering double emulsions can be obtained by homogenizing the contrast-matched oil-in-water Pickering emulsion prepared using the PGMA56-PTFEMA500 nanoparticles with a contrast matched dispersion of hydrophobic poly(lauryl methacrylate)39-poly(2,2,2 trifluoroethyl methacrylate)800 [PLMA39-PTFEMA800] diblock copolymer nanoparticles in n-dodecane. Finally, we show that an isorefractive oil-in-water Pickering emulsion enables fluorescence spectroscopy to be used to monitor the transport of water-insoluble small molecules (pyrene and benzophenone) between n dodecane droplets. Such transport is significantly less efficient than that observed for the equivalent isorefractive surfactant-stabilized emulsion. Conventional turbid emulsions do not enable such a comparison to be made because the intense light scattering leads to substantial spectral attenuation. PMID- 27406978 TI - Density functional calculations reveal a flexible version of the copper paddlewheel unit: implications for metal organic frameworks. AB - Density functional theory calculations on [Cu2(O2CR)4L2] systems reveal a change in ground state with increasing Cu-L bond strength. For L = N-heterocyclic carbene (NHC), the Jahn-Teller axis switches from parallel to orthogonal to the Cu-Cu vector and the copper coordination geometry becomes highly flexible. While the calculated dimer/monomer equilibrium for isolated complexes slightly favours monomers, the preformed paddlewheel units embedded in many metal organic frameworks are potential targets for developing novel materials. PMID- 27406977 TI - Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. AB - Hypervirulent Klebsiella pneumoniae is an emerging cause of community-acquired pyogenic liver abscess. First described in Asia, it is now increasingly recognized in Western countries, commonly afflicting those with Asian descent. This raises the question of genetic predisposition versus geospecific strain acquisition. We leveraged on the Antibiotics for Klebsiella Liver Abscess Syndrome Study (A-KLASS) clinical trial ongoing in ethnically diverse Singapore, to prospectively examine the profiles of 70 patients together with their isolates' genotypic and phenotypic characteristics. The majority of isolates belonged to capsule type K1, a genetically homogenous group corresponding to sequence-type 23. The remaining K2, K5, K16, K28, K57 and K63 isolates as well as two novel cps isolates were genetically heterogeneous. K1 isolates carried higher frequencies of virulence-associated genes including rmpA (regulator of mucoid phenotype A), kfu (Klebsiella ferric uptake transporter), iuc (aerobactin), iro (salmochelin) and irp (yersiniabactin) than non-K1 isolates. The Chinese in our patient cohort, mostly non-diabetic, had higher prevalence of K1 infection than the predominantly diabetic non-Chinese (Malays, Indian and Caucasian). This differential susceptibility to different capsule types among the various ethnic groups suggests patterns of transmission (e.g. environmental source, familial transmission) and/or genetic predisposition unique to each race despite being in the same geographical location. PMID- 27406979 TI - Cardiac resynchronization therapy guided by multimodality cardiac imaging. AB - AIMS: Up to 30-45% of implanted patients are non-responders to CRT. We evaluated the role of a 'CRT team' using cardiac magnetic resonance (CMR) and longitudinal myocardial strain to identify the target area defined as the most delayed and viable region for LV pacing. METHODS AND RESULTS: A total of 100 heart failure patients candidates for CRT divided into two groups were enrolled. Group 1 consisted of 50 consecutive patients scheduled for CRT and prospectively included. Group 2 (control) consisted of 50 patients with a CRT device implanted according to standard clinical practice and matched for age, sex, and LVEF with group 1. Patients were evaluated at baseline and at 6-month follow-up. In group 1, patients underwent two-dimensional speckle-tracking assessment of longitudinal myocardial strain and CMR imaging to identify the target area for LV lead pacing. A positive response to CRT was defined as a reduction of >=15% of the LV end systolic volume at 6-month follow-up. A total of 39 (78%) patients of group 1 were classified as responders to CRT whilst in group 2, only 28 (56%) were responders (P = 0.019). The 'CRT team' identified as target for LV pacing the lateral area in 30 (60%) patients, and the anterolateral or posterolateral areas in 12 (24%) patients. In 8 (16%) patients, the target was far from the lateral area, in the anterior or posterior areas. The patients with concordant position exhibited the highest positive response (93.1%) to CRT. CONCLUSIONS: Multimodality cardiac imaging as a guide for CRT implantation is useful to increase response rate. PMID- 27406981 TI - Data Integration for Integrated Research and Care. AB - A national German funding initiative for Medical Informatics focusing at data integration for medicine gives an opportunity to reopen a window to Germany. In the open window appears a best paper selection of the 2015 annual conference of the German Society of Medical Informatics, Biometry and Epidemiology and papers of the German journal GMS Medical Informatics, Biometry and Epidemiology (MIBE). The publications in focus deal with data integration by transferring clinical routine data into an electronic data capture (EDC) system, using natural language processing to make unstructured date processable, measuring quality of record linkage, and by using a unified metadata scheme for integrated documentation in laboratories. Two additional papers present methods for data analysis especially for change point detection in binary sequences and for analyzing categorial data. PMID- 27406982 TI - Is primiparity a risk factor for advanced maternal age pregnancies? AB - OBJECTIVE: Currently, more women are delaying childbearing until their 40s.This study compared the pregnancy and maternal features, pregnancy and foetal outcomes between multiparous and primiparous patients. We compared the same factors between assisted reproductive technology (ART) and non-ART primiparous patients because of the high proportion of ART used in the primiparous patients. METHODS: The study retrospectively examined 1680 patients, 35 years of age and older, between March 2008 and February 2015. RESULTS: Comparing the features of these two groups, there was an increased incidence of employment and the use of ART in primiparous patients, while birthweight tended to be higher in the multiparous group. There were no significant differences in pregnancy complications other than hypertension disorders, such as pre-eclampsia and HELLP syndrome, which were significantly more frequent in primiparous patients. The rates of foetal growth retardation and perinatal death were significantly higher in primiparous women. Comparison of the data between ART and non-ART primiparous patients indicated that the ART group had a higher initial body mass index and a lower smoking rate. No significant differences in pregnancy complications or foetal outcome were observed between these two groups. CONCLUSION: Primiparity is associated with increased pregnancy and foetal complications in advanced age pregnancies. However, the use of ART in this age group does not seem to be an additional risk factor. PMID- 27406980 TI - CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells. AB - Targeted genome editing technology can correct the sickle cell disease mutation of the beta-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system can target DNA sequences around the sickle-cell mutation in the beta-globin gene for site-specific cleavage and facilitate precise correction when a homologous donor template is codelivered. Several pairs of TALENs and multiple CRISPR guide RNAs were evaluated for both on-target and off-target cleavage rates. Delivery of the CRISPR/Cas9 components to CD34+ cells led to over 18% gene modification in vitro. Additionally, we demonstrate the correction of the sickle cell disease mutation in bone marrow derived CD34+ hematopoietic stem and progenitor cells from sickle cell disease patients, leading to the production of wild-type hemoglobin. These results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology. PMID- 27406983 TI - A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells. AB - The prognosis of muscle-invasive bladder cancer with metastasis is poor. There have been no therapeutic improvements for many years, and an innovative therapy for muscle-invasive bladder cancer has been awaited to replace the conventional cytotoxic chemotherapy. Here, we show a candidate method for the treatment of bladder cancer. The combined treatment with a novel histone deacetylase (HDAC) inhibitor, OBP-801, and celecoxib synergistically inhibited cell growth and markedly induced apoptosis through the caspase-dependent pathway in high-grade bladder cancer cells. Furthermore, the combined treatment induced expression of death receptor 5 (DR5). We identified that knockdown of DR5 by small interfering RNA (siRNA) significantly suppressed apoptosis by the combined treatment. Therefore, we conjectured that the apoptosis induced by OBP-801 and celecoxib is at least partially dependent on DR5. However, it was interesting that the combined treatment drastically suppressed expression of DR5 ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). These data suggest that there is no involvement of TRAIL in the induction of apoptosis by the combination, regardless of the dependence of DR5. Moreover, xenograft studies using human bladder cancer cells showed that the combined therapy suppressed tumor growth by upregulating expressions of DR5 and Bim. The inhibition of tumor growth was significantly more potent than that of each agent alone, without significant weight loss. This combination therapy provided a greater benefit than monotherapy in vitro and in vivo These data show that the combination therapy with OBP-801 and celecoxib is a potential novel therapeutic strategy for patients with muscle-invasive bladder cancer. Mol Cancer Ther; 15(9); 2066-75. (c)2016 AACR. PMID- 27406984 TI - BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members. AB - Targeting BET bromodomain proteins using small molecules is an emerging anticancer strategy with clinical evaluation of at least six inhibitors now underway. Although MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional antitumor activities are important. Using the EMU-Myc model of B-cell lymphoma, we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of proapoptotic (Bim) and antiapoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1 mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. EMU-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1 resistance phenotype. These studies provide important information on mechanisms of apoptosis induction and resistance to BET inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. Mol Cancer Ther; 15(9); 2030-41. (c)2016 AACR. PMID- 27406985 TI - MOR209/ES414, a Novel Bispecific Antibody Targeting PSMA for the Treatment of Metastatic Castration-Resistant Prostate Cancer. AB - Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains a highly unmet medical need and current therapies ultimately result in disease progression. Immunotherapy is a rapidly growing approach for treatment of cancer but has shown limited success to date in the treatment of mCRPC. We have developed a novel humanized bispecific antibody, MOR209/ES414, built on the ADAPTIR (modular protein technology) platform, to redirect T-cell cytotoxicity toward prostate cancer cells by specifically targeting T cells through CD3epsilon to prostate cancer cells expressing PSMA (prostate-specific membrane antigen). In vitro cross-linking of T cells with PSMA-expressing tumor cells by MOR209/ES414 triggered potent target-dependent tumor lysis and induction of target-dependent T cell activation and proliferation. This activity occurred at low picomolar concentrations of MOR209/ES414 and was effective at low T-effector to tumor target cell ratios. In addition, cytotoxic activity was equivalent over a wide range of PSMA expression on target cells, suggesting that as few as 3,700 PSMA receptors per cell are sufficient for tumor lysis. In addition to high sensitivity and in vitro activity, MOR209/ES414 induced limited production of cytokines compared with other bispecific antibody formats. Pharmacokinetic analysis of MOR209/ES414 demonstrated a serum elimination half-life in NOD/SCID gamma (NSG) mice of 4 days. Administration of MOR209/ES414 in murine xenograft models of human prostate cancer significantly inhibited tumor growth, prolonged survival, and decreased serum prostate-specific antigen levels only in the presence of adoptively transferred human T cells. On the basis of these preclinical findings, MOR209/ES414 warrants further investigation as a potential therapeutic for the treatment of CRPC. Mol Cancer Ther; 15(9); 2155-65. (c)2016 AACR. PMID- 27406986 TI - Concepts to Target MYC in Pancreatic Cancer. AB - Current data suggest that MYC is an important signaling hub and driver in pancreatic ductal adenocarcinoma (PDAC), a tumor entity with a strikingly poor prognosis. No targeted therapies with a meaningful clinical impact were successfully developed against PDAC so far. This points to the need to establish novel concepts targeting the relevant drivers of PDAC, like KRAS or MYC. Here, we discuss recent developments of direct or indirect MYC inhibitors and their potential mode of action in PDAC. Mol Cancer Ther; 15(8); 1792-8. (c)2016 AACR. PMID- 27406987 TI - Diagnosis of Thin-Capped Fibroatheromas in Intravascular Optical Coherence Tomography Images: Effects of Light Scattering. AB - BACKGROUND: Intravascular optical coherence tomography (IVOCT) images are recorded by detecting light backscattered within coronary arteries. We hypothesize that non-thin-capped fibroatheroma (TCFA) causes may scatter light to create the false appearance of IVOCT TCFA. METHODS AND RESULTS: Ten human cadaver hearts were imaged with IVOCT (n=14 coronary arteries). IVOCT and histological TCFA images were coregistered and compared. Of 21 IVOCT TCFAs (fibrous cap <65 MUm, lipid arc >1 quadrant), only 8 were true histological TCFA. Foam cell infiltration was responsible for 70% of false IVOCT TCFA and caused both thick capped fibroatheromas to appear as TCFA, and the appearance of TCFAs when no lipid core was present. Other false IVOCT TCFA causes included smooth muscle cell rich fibrous tissue (12%) and loose connective tissue (9%). If the lipid arc >1 quadrant (obtuse) criterion was disregarded, 45 IVOCT TCFAs were identified, and sensitivity of IVOCT TCFA detection increased from 63% to 87%, and specificity remained high at 92%. CONCLUSIONS: We demonstrate that IVOCT can exhibit 87% (95% CI, 75%-93%) sensitivity and 92% specificity (95% CI, 86%-96%) to detect all lipid arcs (both obtuse and acute, <1 quadrant) TCFA, and we also propose new mechanisms involving light scattering that explain why other plaque components can masquerade as TCFA and cause low positive predictive value of IVOCT for TCFA detection (47% for obtuse lipid arcs). Disregarding the lipid arc >1 quadrant requirement enhances the ability of IVOCT to detect TCFA. PMID- 27406988 TI - Bilateral Internal Thoracic Artery Configuration for Coronary Artery Bypass Surgery: A Prospective Randomized Trial. AB - BACKGROUND: Bilateral internal thoracic arteries (BITA) have demonstrated superior patency and improved survival in patients undergoing coronary artery bypass grafting. However, the optimal configuration for BITA utilization and its effect on long-term outcome remains uncertain. METHODS AND RESULTS: We randomly assigned 304 patients undergoing coronary artery bypass grafting using BITA to either in situ or Y grafting configurations. The primary end point was 3-year angiographic patency. Secondary end points included major adverse cardiac and cerebrovascular events (ie, death from any cause, stroke, myocardial infarction, or repeat revascularization) at 7 years. More coronary targets were able to be revascularized using internal thoracic arteries in patients randomized to Y grafting versus in situ group (3.2+/-0.8 versus 2.4+/-0.5 arteries/patient; P<0.01). The primary end point did not show significant differences in graft patency between groups. Secondary end points occurred more frequently in the in situ group (P=0.03), with 7-year rates of 34+/-10% in the in situ and 25+/-12% in the Y grafting groups, driven largely by a higher incidence of repeat revascularization in the in situ group (14+/-4.5% versus 7.4+/-3.2% at 7 years; P=0.009). There were no significant differences in hospital mortality or morbidity or in late survival, myocardial infarction, or stroke between groups. CONCLUSIONS: Three-year systematic angiographic follow-up revealed no significant difference in graft patency between the 2 BITA configurations. However, compared with in situ configuration, the use of BITA in a Y grafting configuration results in lower rates of major adverse cardiovascular and cerebrovascular events at 7 years. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01666366. PMID- 27406989 TI - Letter by Chugh et al Regarding Article, "The Rotterdam Radial Access Research: Ultrasound-Based Radial Artery Evaluation for Diagnostic and Therapeutic Coronary Procedures". PMID- 27406990 TI - Response by Costa et al to Letter Regarding Article, "The Rotterdam Radial Access Research: Ultrasound-Based Radial Artery Evaluation for Diagnostic and Therapeutic Coronary Procedures". PMID- 27406991 TI - Understanding Why and When Optical Coherence Tomography Does Not Detect Vulnerable Plaques: Is It Important? PMID- 27406992 TI - Advanced nanoporous TiO2 photocatalysts by hydrogen plasma for efficient solar light photocatalytic application. AB - We report an effect involving hydrogen (H2)-plasma-treated nanoporous TiO2(H TiO2) photocatalysts that improve photocatalytic performance under solar-light illumination. H-TiO2 photocatalysts were prepared by application of hydrogen plasma of assynthesized TiO2(a-TiO2) without annealing process. Compared with the a-TiO2, the H-TiO2 exhibited high anatase/brookite bicrystallinity and a porous structure. Our study demonstrated that H2 plasma is a simple strategy to fabricate H-TiO2 covering a large surface area that offers many active sites for the extension of the adsorption spectra from ultraviolet (UV) to visible range. Notably, the H-TiO2 showed strong .OH free-radical generation on the TiO2 surface under both UV- and visible-light irradiation with a large responsive surface area, which enhanced photocatalytic efficiency. Under solar-light irradiation, the optimized H-TiO2 120(H2-plasma treatment time: 120 min) photocatalysts showed unprecedentedly excellent removal capability for phenol (Ph), reactive black 5(RB 5), rhodamine B (Rho B) and methylene blue (MB) - approximately four-times higher than those of the other photocatalysts (a-TiO2 and P25) - resulting in complete purification of the water. Such well-purified water (>90%) can utilize culturing of cervical cancer cells (HeLa), breast cancer cells (MCF-7), and keratinocyte cells (HaCaT) while showing minimal cytotoxicity. Significantly, H-TiO2 photocatalysts can be mass-produced and easily processed at room temperature. We believe this novel method can find important environmental and biomedical applications. PMID- 27406994 TI - CFTR targeting during activation of human neutrophils. AB - Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, plays critical roles in phagocytic host defense. However, how activated neutrophils regulate CFTR channel distribution subcellularly is not well defined. To investigate, we tested multiple Abs against different CFTR domains, to examine CFTR expression in human peripheral blood neutrophils by flow cytometry. The data confirmed that resting neutrophils had pronounced CFTR expression. Activation of neutrophils with soluble or particulate agonists did not significantly increase CFTR expression level, but induced CFTR redistribution to cell surface. Such CFTR mobilization correlated with cell-surface recruitment of formyl-peptide receptor during secretory vesicle exocytosis. Intriguingly, neutrophils from patients with DeltaF508-CF, despite expression of the mutant CFTR, showed little cell-surface mobilization upon stimulation. Although normal neutrophils effectively targeted CFTR to their phagosomes, DeltaF508-CF neutrophils had impairment in that process, resulting in deficient hypochlorous acid production. Taken together, activated neutrophils regulate CFTR distribution by targeting this chloride channel to the subcellular sites of activation, and DeltaF508-CF neutrophils fail to achieve such targeting, thus undermining their host defense function. PMID- 27406993 TI - Class 3 semaphorins induce F-actin reorganization in human dendritic cells: Role in cell migration. AB - Class 3 semaphorins (Semas) are soluble proteins that are well recognized for their role in guiding axonal migration during neuronal development. In the immune system, Sema3A has been shown to influence murine dendritic cell (DC) migration by signaling through a neuropilin (NRP)-1/plexin-A1 coreceptor axis. Potential roles for class 3 Semas in human DCs have yet to be described. We tested the hypothesis that Sema3A, -3C, and -3F, each with a unique NRP-1 and/or NRP-2 binding specificity, influence human DC migration. In this report, we find that although NRP-1 and NRP-2 are expressed in human immature DCs (imDCs), NRP-2 expression increases as cells mature further, whereas expression of NRP-1 declines dramatically. Elevated levels of RNA encoding plexin-A1 and -A3 are present in both imDCs and mature DC (mDCs), supporting the relevance of Sema/NRP/plexin signaling pathways in these cells. Sema3A, -3C, and -3F bind to human DCs, with Sema3F binding predominantly through NRP-2. The binding of these Semas leads to reorganization of actin filaments at the plasma membrane and increased transwell migration in the absence or presence of chemokine CCL19. Microfluidic chamber assays failed to demonstrate consistent changes in speed of Sema3C-treated DCs, suggesting increased cell deformability as a possible explanation for enhanced transwell migration. Although monocytes express RNA encoding Sema3A, -3C, and -3F, only RNA encoding Sema3C increases robustly during DC differentiation. These data suggest that Sema3A, -3C, and -3F, likely with coreceptors NRP-1, NRP-2, and plexin-A1 and/or -A3, promote migration and possibly other activities of human DCs during innate and adaptive immune responses. PMID- 27406995 TI - Angiogenesis and wound repair: when enough is enough. AB - All animals heal, and the ability to heal is requisite for human health. One aspect of repair that has always been considered to be essential for adequate healing is the creation of a new vasculature via angiogenesis. As adult skin wounds heal, a period of rapid and robust capillary growth creates a vascular bed that has many fold more capillaries than does normal tissue. Over time, most of the newly formed capillaries regress, resulting in a final vascular density similar to that of normal skin. Certainly, new capillaries are necessary to bring nutrients, immune cells, and oxygen to healing wounds. Yet, the presumed functional importance of an overabundance of capillaries has recently been challenged, creating questions about whether excess capillary growth is truly necessary for healing. In particular, studies of wounds that heal exceptionally quickly and with less scar formation, such as those in fetal skin and oral mucosa, show that these tissues heal with a reduced angiogenic burst composed of more mature vessels that provide better oxygenation. The level of angiogenesis in wounds often correlates with the inflammatory response, largely because inflammatory cells produce an abundance of proangiogenic mediators. Both the selective reduction of inflammation and the selective reduction of angiogenesis have now been suggested as ways to improve scarring. These concepts link excessive inflammation and the production of a dense but poorly perfused capillary bed to inferior healing outcomes. PMID- 27406996 TI - Elite controller CD8+ T cells exhibit comparable viral inhibition capacity, but better sustained effector properties compared to chronic progressors. AB - Mechanisms modulating HIV-specific CD8+ T cell-mediated viral inhibition are not well defined. To delineate features of effective control, we compared the ability of CD8+ T cells from HIV ECs and CPs to inhibit HIV ex vivo. ECs showed superior inhibition compared to HAART-treated or untreated CPs in a typical VIA in which CD8+ T cells are rested 3 d before use (P = 0.025). In contrast, comparable antiviral activity was observed in freshly thawed cells. Rested CD8+ T cells underwent apoptosis with preferential loss of HIV-specific cells. EC CD8+ T cells showed greater capacity to sustain polyfunctionality ex vivo compared with those of CPs, and incubation of CD8+ T cells with IL-15 augmented inhibition. These results indicate that superior ex vivo inhibition of viral replication by CD8+ T cells from ECs is associated with enhanced retention of functional qualities and that in vitro antiviral function is enhanced by IL-15. PMID- 27406998 TI - Inhibition of FGF Signalling Pathway Augments the Expression of Pluripotency and Trophoblast Lineage Marker Genes in Porcine Parthenogenetic Blastocyst. AB - The consistent failure to isolate bona fide pluripotent cell lines from livestock indicates that the underlying mechanisms of early lineage specification are poorly defined. Unlike other species, the contrivances of segregation have been comprehensively studied in the mouse. In mouse, FGF/MAPK signalling pathway dictates the segregation of hypoblast (primitive endoderm). However, it is not evident whether this mechanism is also conserved in livestock. Here, in this study, we examined the roles of FGF/MAP kinase signalling pathways in porcine parthenogenetic embryos during the early development. Porcine parthenogenetic embryos were cultured in the medium addition with FGFR inhibitor BGJ398 (10 MUm) or DEMOS. Pluripotency- and lineage-related gene expressions in the early porcine embryos were determined. Compared to control, total cell numbers on day 7 were significantly higher (55 +/- 5.96 vs 47 +/- 1.97, p < 0.05) in embryos cultured in the presence of BGJ398, but had no significant effect on the rate of blastocyst development (47% vs 44%, p > 0.05). Nonetheless, BGJ398 treatment significantly augmented the expression of pluripotency and trophoblast marker genes (SOX2, OCT4, KLF4 and CDX2), but did not significantly change the expression of NANOG and hypoblast marker gene (GATA4). Furthermore, the addition of FGF signalling agonist (FGF2) during the embryo development significantly decreased the expression of pluripotency and trophoblast marker genes (SOX2, NANOG, KLF4 and CDX2), but no significant effect on the expression of OCT4 and GATA4 was observed. Here, we exhibit that inhibition of FGF signalling could improve the quality of the porcine embryo and escalate the chance to capture pluripotency. Besides, it also promotes the trophoblast development of porcine parthenogenetic embryo. In addition, the data suggested that FGF signalling pathway is dispensable for the segregation of hypoblast and epiblast lineages in porcine embryo during the early development. PMID- 27407000 TI - Graphic illustration of a potential problem: a commentary on Morrissey (2016). PMID- 27407001 TI - Cooperative Ordering and Kinetics of Cellulose Nanocrystal Alignment in a Magnetic Field. AB - Cellulose nanocrystals (CNCs) are emerging nanomaterials that form chiral nematic liquid crystals above a critical concentration (C*) and additionally orient within electromagnetic fields. The control over CNC alignment is significant for materials processing and end use; to date, magnetic alignment has been demonstrated using only strong fields over extended or arbitrary time scales. This work investigates the effects of comparatively weak magnetic fields (0-1.2 T) and CNC concentration (1.65-8.25 wt %) on the kinetics and degree of CNC ordering using small-angle X-ray scattering. Interparticle spacing, correlation length, and orientation order parameters (eta and S) increased with time and field strength following a sigmoidal profile. In a 1.2 T magnetic field for CNC suspensions above C*, partial alignment occurred in under 2 min followed by slower cooperative ordering to achieve nearly perfect alignment in under 200 min (S = -0.499 where S = -0.5 indicates perfect antialignment). At 0.56 T, nearly perfect alignment was also achieved, yet the ordering was 36% slower. Outside of a magnetic field, the order parameter plateaued at 52% alignment (S = -0.26) after 5 h, showcasing the drastic effects of relatively weak magnetic fields on CNC alignment. For suspensions below C*, no magnetic alignment was detected. PMID- 27406999 TI - CHIP(-/-)-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications. AB - Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2 terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP(-/-)-mice over the first 8-9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin 5'-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKalpha1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKalpha2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP(-/-)-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models. PMID- 27407002 TI - The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study. AB - BACKGROUND: There is a relationship between liver stiffness measurement (LSM) and outcome of HCV patients. AIM: To evaluate the performance of LSM to predict outcome of HCV patients at risk of liver-related complication. METHODS: We established a retrospective longitudinal cohort of 341 HCV patients with unequivocal cirrhosis. All underwent LSM and were followed from September 2006 to July 2015. Outcome measure was a composite end-point of end-stage liver disease (ESLD) and/or hepatocellular carcinoma (HCC). Cox models and areas under receiver operating characteristic (AUROC) curves were used to evaluate independent risk factors of outcome. RESULTS: Overall, LSM was below the 12.5 kPa threshold in 129 (37.8%) patients, including three-fourth and one-third of patients with or without a sustained virological response respectively. Liver disease progressed in 136 (39.9%) patients after a median observational period of 23.5 months. Older age, male gender, alcohol use disorders, metabolic syndrome and LSM were independent risk factors of liver disease progression. Age, alcohol use disorders and LSM were independently associated with ESLD. Age, gender and metabolic syndrome, but not LSM, were associated with HCC. The AUROC curves for disease progression, ESLD and HCC were 0.67, 0.70 and 0.58 respectively. Patients with a liver stiffness >12.5 kPa were at the highest risk of liver disease progression; below 12.5 kPa, liver stiffness was not discriminant. CONCLUSION: Liver stiffness measurement is not a surrogate of disease progression of HCV patients with cirrhosis. HCV patients with cirrhosis should undergo the recommended follow-up, regardless of liver stiffness measurement. PMID- 27407003 TI - From clinical imaging and computational models to personalised medicine and image guided interventions. AB - This short paper describes the development of the UCL Centre for Medical Image Computing (CMIC) from 2006 to 2016, together with reference to historical developments of the Computational Imaging sciences Group (CISG) at Guy's Hospital. Key early work in automated image registration led to developments in image guided surgery and improved cancer diagnosis and therapy. The work is illustrated with examples from neurosurgery, laparoscopic liver and gastric surgery, diagnosis and treatment of prostate cancer and breast cancer, and image guided radiotherapy for lung cancer. PMID- 27407004 TI - Computer Aided Orthopaedic Surgery: Incremental shift or paradigm change? AB - Computer Aided Orthopaedic Surgery (CAOS) is now about 25 years old. Unlike Neurosurgery, Computer Aided Surgery has not become the standard of care in Orthopaedic Surgery. In this paper, we provide the technical and clinical context raised by this observation in an attempt to elucidate the reasons for this state of affairs. We start with a brief outline of the history of CAOS, review the main CAOS technologies, and describe how they are evaluated. We then identify some of the current publications in the field and present the opposing views on their clinical impact and their acceptance by the orthopaedic community worldwide. We focus on total knee replacement surgery as a case study and present current clinical results and contrasting opinions on CAOS technologies. We then discuss the challenges and opportunities for research in medical image analysis in CAOS and in musculoskeletal radiology. We conclude with a suggestion that while CAOS acceptance may be more moderate than that of other fields in surgery, it still has a place in the arsenal of useful tools available to orthopaedic surgeons. PMID- 27407005 TI - Fmoc solid-phase synthesis of C-terminal modified peptides by formation of a backbone cyclic urethane moiety. AB - C-terminally modified peptides are of high significance due to the therapeutic properties that accompany various C-terminal functional groups and the ability to manipulate them for further applications. Thus, there is a great necessity for an effective solid phase technique for the synthesis of C-terminally modified peptides. Here, we report a universal solid phase strategy for the synthesis of various C-terminal modified peptides which is independent of the type of resins, linkers, and unnatural moieties typically needed for C-terminal modifications. The technique proceeds by the modification of C-terminal serine to a cyclic urethane moiety which results in the activation of the backbone amide chain for nucleophilic displacement by various nucleophiles to generate C-terminally modified acids, esters, N-aryl amides, and alcohols. This cyclic urethane technique (CUT) also provides a general strategy for synthesis of C-terminal protected peptides that can be used for convergent synthesis of large peptides. The C-terminal protecting groups are cleaved by facile hydrolysis to release the free peptide. PMID- 27407006 TI - Filamin A regulates the organization and remodeling of the pericellular collagen matrix. AB - Extracellular matrix remodeling by cell adhesion-related processes is critical for proliferation and tissue homeostasis, but how adhesions and the cytoskeleton interact to organize the pericellular matrix (PCM) is not understood. We examined the role of the actin-binding protein, filamin A (FLNa), in pericellular collagen remodeling. Compared with wild-type (WT), mice with fibroblast-specific deletion of FLNa exhibited higher density but reduced organization of collagen fibers after increased loading of the periodontal ligament for 2 wk. In cultured fibroblasts, FLNa knockdown (KD) did not affect collagen mRNA, but after 24 h of culture, FLNa WT cells exhibited ~2-fold higher cell-surface collagen KD cells and 13-fold higher levels of activated beta1 integrins. In FLNa WT cells, there was 3-fold more colocalization of talin with pericellular cleaved collagen than in FLNa KD cells. MMP-9 mRNA and protein expression were >2-fold higher in FLNa KD cells than in WT cells. Cathepsin B, which is necessary for intracellular collagen digestion, was >3-fold higher in FLNa WT cells than in KD cells. FLNa WT cells exhibited 2-fold more collagen phagocytosis than KD cells, which involved the FLNa actin-binding domain. Evidently, FLNa regulates PCM remodeling through its effects on degradation pathways that affect the abundance and organization of collagen.-Mezawa, M., Pinto, V. I., Kazembe, M. P., Lee, W. S., McCulloch, C. A. Filamin A regulates the organization and remodeling of the pericellular collagen matrix. PMID- 27407007 TI - Ring-polymer molecular dynamical calculations for the F + HCl -> HF + Cl reaction on the ground 12A' potential energy surface. AB - The reaction kinetics of the heavy-light-heavy abstraction reaction F + HCl -> HF + Cl on the ground electronic state potential energy surface (PES) is investigated theoretically by a recently developed ring polymer molecular dynamics (RPMD) approach. First, a new PES is developed by the permutation invariant polynomial neural network (PIP-NN) approach based on 30 620 points sampled over a large configuration space from the latest and most accurate Deskevich-Hayes-Takahashi-Skodje-Nesbitt (DHTSN) PES (J. Chem. Phys., 2006, 124, 224303). Excellent fitting performance was achieved with only 521 parameters. The PIP-NN PES is 11 times faster than the DHTSN PES. Besides, the first analytical derivatives with respect to the coordinates of the atoms have been obtained for the PIP-NN PES. The RPMD rate coefficients on the PIP-NN PES are calculated and compared with available theoretical and experimental results. It is found that the experimental rate coefficients are significantly larger than the theoretical results on the DHTSN PES, due to its overestimated reaction barrier. We conclude that a reliable PES for this important heavy-light-heavy reaction is highly desirable. PMID- 27407008 TI - Transient expression in Nicotiana benthamiana for rapid functional analysis of genes involved in non-photochemical quenching and carotenoid biosynthesis. AB - Plants must switch rapidly between light harvesting and photoprotection in response to environmental fluctuations in light intensity. This switch can lead to losses in absorbed energy usage, as photoprotective energy dissipation mechanisms can take minutes to hours to fully relax. One possible way to improve photosynthesis is to engineer these energy dissipation mechanisms (measured as non-photochemical quenching of chlorophyll a fluorescence, NPQ) to induce and relax more quickly, resulting in smaller losses under dynamic light conditions. Previous studies aimed at understanding the enzymes involved in the regulation of NPQ have relied primarily on labor-intensive and time-consuming generation of stable transgenic lines and mutant populations - approaches limited to organisms amenable to genetic manipulation and mapping. To enable rapid functional testing of NPQ-related genes from diverse organisms, we performed Agrobacterium tumefaciens-mediated transient expression assays in Nicotiana benthamiana to test if NPQ kinetics could be modified in fully expanded leaves. By expressing Arabidopsis thaliana genes known to be involved in NPQ, we confirmed the viability of this method for studying dynamic photosynthetic processes. Subsequently, we used naturally occurring variation in photosystem II subunit S, a modulator of NPQ in plants, to explore how differences in amino acid sequence affect NPQ capacity and kinetics. Finally, we functionally characterized four predicted carotenoid biosynthesis genes from the marine algae Nannochloropsis oceanica and Thalassiosira pseudonana and examined the effect of their expression on NPQ in N. benthamiana. This method offers a powerful alternative to traditional gene characterization methods by providing a fast and easy platform for assessing gene function in planta. PMID- 27407009 TI - Two Mechanisms of Tip Enhancement of Raman Scattering by Protein Aggregates. AB - Tip-enhanced Raman spectroscopy (TERS) is a powerful tool for probing the surface of biological species with nanometer spatial resolution. Here, we report the TER spectra of an individual insulin fibril, the protein cast film and a short peptide (LVEALYL) microcrystal mimicking the fibril core. Two different types of TER spectra were acquired depending on the "roughness" of the probed surface at the molecular level. A fully reproducible, low-intensity, normal Raman-type spectrum was characteristic of the top flat surface of the microcrystal while highly variable, higher intensity TER spectra were obtained for the edges of the microcrystal, cast film, and fibril. As a result, two tip enhancement mechanisms of Raman scattering, long- and short-range, were proposed by analogy with the physical and chemical enhancement mechanisms, respectively, known for surface enhanced Raman spectroscopy. PMID- 27407010 TI - Characterization of Thermal Oxides on 4H-SiC Epitaxial Substrates Using Fourier Transform Infrared Spectroscopy. AB - Fourier transform infrared (FT-IR) spectra were measured for thermal oxides with different electrical properties grown on 4H-SiC substrates. The peak frequency of the transverse optical (TO) phonon mode was blue-shifted by 5 cm-1 as the oxide layer thickness decreased to 3 nm. The blue shift of the TO mode indicates interfacial compressive stress in the oxide. Comparison of data for the oxide on a SiC substrate with that for similar oxides on a Si substrate implies that the peak shift of the TO mode at the SiO2/SiC interface is larger than that of SiO2/Si, which suggests that the interfacial stress for the oxide on the SiC substrate is larger than that on the Si substrate. For the SiO2/SiC interfacial region (<3 nm oxide thickness), despite the fact that the blue shift of the TO modes becomes larger while approaching the oxide/SiC interface, the peak frequency of the TO modes red-shifts at the oxide/SiC interface. The peak frequency shift of the TO mode for the sample without post-oxidation annealing was larger than that for the samples post-annealed in a nitric oxide atmosphere. The channel mobilities are correlated with the degree of shift of the TO mode when the oxide thickness is <3 nm. It appears that the compressive stress at the SiO2/SiC interface generates silicon suboxide components and weakens the Si-O bonds. As the result, the TO mode was red-shifted and the oxygen deficiency increased to relax the compressive stress in the oxide with <3 nm thickness. Fourier transform infrared spectroscopy measurements provide unique and useful information about stress and inhomogeneity at the oxide/SiC interface. PMID- 27407011 TI - Arthroscopically blind anatomical anterior cruciate ligament reconstruction using only navigation guidance: a cadaveric study. AB - BACKGROUND: To develop a preoperative planning and navigation system for anatomic anterior cruciate ligament (ACL) reconstruction and to evaluate the accuracy and the efficacy of anatomical ACL reconstruction using only navigation guidance. METHODS: A three-dimensional (3D) preoperative planning and navigation system was developed from open source libraries. Twenty knees from 10 fresh-frozen human cadavers underwent navigation-only guided double-bundle ACL reconstruction using the transportal technique. A computed tomography (CT) scan was performed after ACL reconstruction to create a 3D surface model of the distal femur. We evaluated the tunnel position by Bernard's quadrant method, the tunnel orientation by measuring the tunnel angle in three projected planes, and the incidence of posterior cortical damage. Then, we compared preoperative planning with the postoperative results. RESULTS: The difference in tunnel position between preoperative planning and the postoperative results was a mean of 2.50+/-1.75mm (range, 0.77 to 5.85mm) in the anteromedial (AM) tunnel and a mean of 3.53+/ 2.20mm (range, 0.39 to 7.92mm) in the posterolateral (PL) tunnel. The difference in tunnel orientation was a mean of 6.74+/-6.70 degrees (range, 0.35 to 25.6 degrees ) in the AM tunnel and a mean of 5.73+/-3.51 degrees (range, 1.58 to 15.04 degrees ) in the PL tunnel. No statically significant difference was observed. Posterior cortical damage developed in seven cases (35%). CONCLUSIONS: Our navigation-only guided ACL reconstruction produced consistent femoral tunnel position and orientation results. The accuracy and consistency of femoral tunneling were improved by using the preoperative planning and navigation system. PMID- 27407012 TI - Direct Observation of Excimer-Mediated Intramolecular Electron Transfer in a Cofacially-Stacked Perylene Bisimide Pair. AB - We have elucidated excimer-mediated intramolecular electron transfer in cofacially stacked PBIs tethered by two phenylene-butadiynylene loops. The electron transfer between energetically equivalent PBIs is revealed by the simultaneous observation of the PBI radical anion and cation bands in the transient absorption spectra. The fluorescence decay time of the excimer states is in good agreement with the rise time of PBI radical bands in transient absorption spectra suggesting that the electron transfer dynamics proceed via the excimer state. We can conclude that the excimer state effectuates the efficient charge transfer in the cofacially stacked PBI dimer. PMID- 27407013 TI - Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. AB - AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin and 13 empagliflozin) involving 30 384 patients, with follow-ups ranging from 24 to 160 weeks, were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture events was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR 1.15; 95% CI 0.71-1.88), dapagliflozin (OR 0.68; 95% CI 0.37-1.25) and empagliflozin (OR 0.93; 95% CI 0.74 1.18) were not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of the null findings with regard to SGLT2 inhibitors. CONCLUSIONS: Our meta-analysis based on available RCT data does not support the harmful effect of SGLT2 inhibitors on fractures, although future safety monitoring from RCTs and real-world data with detailed information on bone health is warranted. PMID- 27407015 TI - The evaluation of the accuracy of shape imaging of prosthetic abutment. AB - PURPOSE: The aim of the study was the in vitro evaluation of the accuracy of shape imaging of abutment teeth using different impression compounds. METHODS: To compare the accuracy of the shape of the numerically imaged real prosthetic abutments with the tested models of abutments obtained with the replica technique, the Geomagic Qualify program was applied. Making use of the licensed program Statistica, statistical analysis of the results obtained was conducted. RESULTS: In the research procedures, analyses were conducted for 10 abutment premolars and 10 abutment molars. The tests allowed us to state that the dimensional accuracy of the models of prosthetic abutments obtained with the application of elastic compounds tested ensures comparable shape imaging. CONCLUSIONS: The objective method developed and applied here is suitable for controlling the imaging of the abutment teeth. The Geomagic Qualify program that was used during the research is a reliable tool of 3D analysis for the estimation of procedure of abutment tooth preparation and indication of an error of shape of prepared occlusal surface, lateral surface of abutment and errors of shaping the chamfer zone. PMID- 27407014 TI - Silk fibroin scaffolds with inverse opal structure for bone tissue engineering. AB - How scaffold porosity, pore diameter and geometry influence cellular behavior is although heavily researched - merely understood, especially in 3D. This is mainly caused by a lack of suitable, reproducible scaffold fabrication methods, with processes such as gas foaming, lyophilization or particulate leaching still being the standard. Here we propose a method to generate highly porous silk fibroin scaffolds with monodisperse spherical pores, namely inverse opals, and study their effect on cell behavior. These silk fibroin inverse opal scaffolds were compared to salt-leached silk fibroin scaffolds in terms of human mesenchymal stem cell response upon osteogenic differentiation signals. While cell number remained similar on both scaffold types, extracellular matrix mineralization nearly doubled on the newly developed scaffolds, suggesting a positive effect on cell differentiation. By using the very same material with comparable average pore diameters, this increase in mineral content can be attributed to either the differences in pore diameter distribution or the pore geometry. Although the exact mechanisms leading to enhanced mineralization in inverse opals are not yet fully understood, our results indicate that control over pore geometry alone can have a major impact on the bioactivity of a scaffold toward stem cell differentiation into bone tissue. (c) 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2074-2084, 2017. PMID- 27407016 TI - Appropriateness and avoidability of terminal hospital admissions: Results of a survey among family physicians. AB - BACKGROUND: Although the acute hospital setting is not considered to be an ideal place of death, many people are admitted to hospital at the end of life. AIM: To examine what proportion of terminal hospital admissions among their patients family physicians consider to have been avoidable and/or inappropriate; which patient, family physician and admission factors are associated with the perceived inappropriateness or avoidability of terminal hospital admissions; and which interventions could have prevented them, from the perspective of family physicians. DESIGN: Survey among family physicians, linked to medical record data. SETTING: Patients who had died non-suddenly in the acute hospital setting of a university hospital in Belgium between January and August 2014. RESULTS: We received 245 completed questionnaires (response rate 70%) and 77% of those hospital deaths ( n = 189) were considered to be non-sudden. Almost 14% of all terminal hospital admissions were considered to be potentially inappropriate, almost 14% potentially avoidable and 8% both, according to family physicians. The terminal hospital admission was more likely to be considered potentially inappropriate or potentially avoidable for patients who had died of cancer, when the patient's life expectancy at the time of admission was limited, by family physicians who had had palliative care training at basic, postgraduate or post academic level, and when the admission was initiated by the patient, partner or other family. CONCLUSION: Timely communication with the patient about their limited life expectancy and the provision of better support to family caregivers may be important strategies in reducing the number of hospital deaths. PMID- 27407017 TI - Synthesis and in vivo Evaluation of Fluorine-18 and Iodine-123 Pyrazolo[4,3-e] 1,2,4-triazolo[1,5-c]pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A2A Receptors. AB - Imaging agents that target adenosine type 2A (A2A ) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson's disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A2A receptor density and function in neurodegenerative diseases. We previously described the successful evaluation of two A2A -specific radiotracers in both nonhuman primates and in subsequent human clinical trials: [(123) I]MNI-420 and [(18) F]MNI-444. Herein we describe the development of both of these radiotracers by selection from a series of A2A ligands, based on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5 c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine-18 or iodine-123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7-(2-(4-(4-(2-[(18) F]fluoroethoxy)phenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl) 7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine ([(18) F]MNI-444) and 7 (2-(4-(2-fluoro-4-[(123) I]iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-amine ([(123) I]MNI-420) as PET and SPECT radiopharmaceuticals for mapping A2A receptors in brain. PMID- 27407019 TI - Introgression of null allele of Kunitz trypsin inhibitor through marker-assisted backcross breeding in soybean (Glycine max L. Merr.). AB - BACKGROUND: Presence of Kunitz trypsin inhibitor (KTI) in soybean seeds necessitates pre-heat treatment of the soy-flour for its inactivation before using it in food and feed products. The heat treatment not only enhances processing costs of the soy-based foods and feeds but also affects seed-protein quality and solubility. Genetic elimination of KTI is an important and effective approach. Therefore, molecular marker-assisted backcross breeding (MABB) approach was adopted for genetic elimination of KTI from two popular soybean genotypes, DS9712 and DS9814. PI542044, an exotic germplasm line was used as donor of the kti allele which inhibits functional KTI peptide production. RESULTS: Foreground selection for the kti allele was performed with three closely linked SSR markers while background selection was done with 93 polymorphic SSR markers. Plants in the BC1F1 generation were found to recover 70.4-87.63 % and 60.26-73.78 % of the recurrent parent genome (RPG) of DS9712 and DS9814, respectively. Similarly, selected plants in the BC2F1 generation had 93.01-98.92 % and 83.3-91.67 % recovery of their respective RPGs. Recombinant selection was performed so as to identify plants with minimal linkage drag. Biochemical analysis of the seeds of the selected plants (ktikti) confirmed absence of KTI peptides in the seeds. Phenotypically, the selected plants were comparable to the respective recurrent parent in yield and other traits. CONCLUSIONS: MABB approach helped in speedy development of 6 KTI free breeding lines of soybean. Such lines will be suitable for the farmers and the soybean industries to use in production of soy-based foods and feeds without pre-heat treatment of the soy-flour. It would contribute towards wider acceptability of soy-based foods and feeds. PMID- 27407018 TI - Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance. AB - Steady-state population pharmacokinetics of a noncommercial immediate-release metformin (hydrochloride) drug product were characterized in 28 severely obese children with insulin resistance. The concentration-time profiles with double peaks were well described by a 1-compartment model with 2 absorption sites. Mean population apparent clearance (CL/F) was 68.1 L/h, and mean apparent volume of distribution (V/F) was 28.8 L. Body weight was a covariate of CL/F and V/F. Estimated glomerular filtration rate was a significant covariate of CL/F (P < .001). SLC22A1 genotype did not significantly affect metformin pharmacokinetics. The response to 6 months of metformin treatment (HbA1c , homeostasis model assessment for insulin resistance, fasting insulin, and glucose changes) did not differ between SLC22A1 wild-type subjects and carriers of presumably low-activity SLC22A1 alleles. However, SLC22A1 variant carriers had smaller reductions in percentage of total trunk fat after metformin therapy, although the percentage reduction in trunk fat was small. The median % change in trunk fat was -2.20% ( 9.00% to 0.900%) and -1.20% (-2.40% to 7.30%) for the SLC22A1 wild-type subjects and variant carriers, respectively. Future study is needed to evaluate the effects of SLC22A1 polymorphisms on metformin-mediated weight reduction in obese children. PMID- 27407020 TI - Highly efficient enzyme encapsulation in a protein nanocage: towards enzyme catalysis in a cellular nanocompartment mimic. AB - The study of enzyme behavior in small nanocompartments is crucial for the understanding of biocatalytic processes in the cellular environment. We have developed an enzymatic conjugation strategy to attach a model enzyme to the interior of a cowpea chlorotic mottle virus capsid. It is shown that with this methodology high encapsulation efficiencies can be achieved. Additionally, we demonstrate that the encapsulation does not affect the enzyme performance in terms of a decreased activity or a hampered substrate diffusion. Finally, it is shown that the encapsulated enzymes are protected against proteases. We believe that our strategy can be used to study enzyme kinetics in an environment that approaches physiological conditions. PMID- 27407021 TI - A dynamic view of dynamic indices. AB - Dynamic indices (based on cardiopulmonary interactions in mechanically ventilated patients in sinus rhythm) have been developed as simple tools for predicting fluid responsiveness in the absence of cardiac output monitoring. Although the earliest dynamic indices relied on the invasive measurement of pulse pressure variations or stroke volume variations, the most recently developed indices are based on non-invasive photoplethysmography. However, a number of confounding factors have been found which decrease the clinical value of these indices. The present experts' opinion explains why changes in dynamic indices during hemodynamic maneuvers might be an interesting alternative to using them accurately at bedside. PMID- 27407022 TI - Diaphragmatic ultrasonography as an adjunct predictor tool of weaning success in patients with difficult and prolonged weaning. AB - BACKGROUND: Diaphragmatic ultrasonography has been recently considered as a new weaning predictor method. Previous studies checked diaphragmatic excursion and thickness during quiet or deep breathing in unselected populations of critically ill patients. Our study aimed to investigate diaphragmatic excursion during quiet and unassisted breathing, in comparison to standard predictor tools, such as Rapid Shallow Breathing Index (RSBI) and Maximal Inspiratory Pressure (Pimax), in patients with difficult and/or prolonged weaning. METHODS: Patients with difficult and/or prolonged weaning, who met the criteria for spontaneous breathing trial, were assessed. The excursion of each hemidiaphragm (DEx) was evaluated by B-mode and M-mode ultrasonography while patient was on quiet breathing and at supine position. RSBI and Pimax were simultaneously recorded and weaning outcome was recorded. RESULTS: Thirteen male and fourteen female patients were included. DEx [median and interquartile range, mm] was 14 (8.5-22) for the right hemidiaphragm (RDEx) and 12 (7-23) for the left (LDEx). We found no difference in DEx between sexes. Among the four weaning predictor tools, LDEx at a cut-off 10 mm was the best index to predict weaning success (sensitivity 86%, specificity 85%, Negative Predictive Value 94%). The optimal cut-off values, as determined by the area under the receiver operating characteristic curve, were 10 mm for RDEx, 7 mm for LDEx, 57 breaths/min/L for RSBI and -20 cmH2O for Pimax. CONCLUSIONS: Our results suggest that DEx threshold of 10 mm and 7 mm for right and left hemidiaphragms respectively could be used as adjunct tool in the predictive algorithm of weaning in difficult to wean patients. PMID- 27407023 TI - Unanticipated difficult airway during Montgomery tube removal in an anesthetized patient. PMID- 27407024 TI - Subtractive Color Filters Based on a Silicon-Aluminum Hybrid-Nanodisk Metasurface Enabling Enhanced Color Purity. AB - Highly efficient subtractive tri-color filters of cyan, magenta, and yellow with enhanced color purity and robustness have been proposed and realized, by exploiting a silicon-aluminum (Si-Al) hybrid-nanodisk (ND) metasurface atop a Si substrate. The aspect ratio of the Si-Al hybrid ND is much lower than that of the conventional Si nanowire, which is disadvantageous due to its fragility and low color purity. In response to incident light impinging upon the metasurface, the hybrid-NDs individually play the role in exciting a magnetic dipole (MD) resonance through the mediation of Mie-scattering between the hybrid ND and air. The light stored in the resonance is coupled to the substrate, giving rise to a suppressed reflection. By virtue of the top Al ND, the excited MD resonance is strongly confined by the Si ND. As a consequence, a near-zero resonant dip that exhibits high off-resonance reflection and narrow bandwidth is produced for embodying highly efficient tri-color filters with enhanced color purity. The spectral position can be tuned by a simple adjustment of the hybrid-ND diameter. A full-color palette was successfully created with a high color purity and large color gamut. The proposed devices may be applied for photorealistic high resolution color printing and holographic displays. PMID- 27407025 TI - Long-term outcome and its predictors in giant cell myocarditis. AB - AIMS: There are no studies focusing on prognostic factors in giant cell myocarditis (GCM). We aimed to identify predictors of transplant-free survival in GCM. METHODS AND RESULTS: We analysed the details of 46 patients with GCM (31 women, mean age 51 +/- 12 years) seen at our hospital since 1991 and followed for the occurrence of cardiac death or transplantation till May 2015. The association of transplant-free survival with patient characteristics, laboratory data on admission, and myocardial histology in the 38 patients diagnosed prior to death or transplantation was examined. Altogether 26 patients died (n = 8) or underwent transplantation (n = 18) a median of 11 months following symptom onset. The 5 year estimate of transplant-free survival was 42% [95% confidence interval (CI) 35-48%]. By Cox regression analysis, the hazard ratio for death or transplantation was 0.87 (95% CI 0.75-0.99) per +5% difference in LVEF, 1.06 (95% CI 1.03-1.10) per + 1000 ng/L difference in NT-proBNP, and 4.57 (95% CI 1.63 11.28) for cardiac troponin-T above the median of 85 ng/L at presentation. The severity of necrosis and fibrosis in myocardial biopsy, graded by the consensus of two cardiac pathologists as none, mild, moderate, or severe, predicted the outcome with a hazard ratio of 7.17 (95% CI 2.29-22.40) for the presence of either necrosis or fibrosis of at least moderate extent. CONCLUSIONS: In GCM, the probability of transplant-free survival is 42% at 5 years from symptom onset. Markers of myocyte injury and cardiac dysfunction help predict the outcome. PMID- 27407026 TI - Steady-state droplet size in montmorillonite stabilised emulsions. AB - The formation of hexadecane-in-water emulsions stabilised by montmorillonite platelets was studied. In this system the platelets form a monolayer around the droplets and the droplet size decreases with increasing platelet volume fraction. However, the number of platelets present exceeds that required for monolayer coverage. The kinetics of emulsification were investigated and coalescence of droplets during turbulent mixing was found to continue even after the droplets had reached their ultimate size. Non-spherical droplets, resulting from arrested coalescence, were not observed suggesting that particles may be desorbing from the interface during the turbulent flow. A kinetic model based on a competition between droplet break-up and coalescence, mediated by particle adsorption and desorption, reproduces experimental trends in droplet diameter. The model can be used to predict the most efficient formulation to minimise droplet diameters for given materials and mixing conditions and sheds light on the processes occurring during emulsification in this system. PMID- 27407027 TI - Risk Factors for Infection After Knee Arthroscopy: Analysis of 595,083 Cases From 3 United States Databases. AB - PURPOSE: To identify and quantify patient- and procedure-related risk factors for post-arthroscopic knee infections using a large dataset. METHODS: An administrative health care database including 8 years of records from 2 large commercial insurers and Medicare (a 5% random sample) was queried to identify all knee arthroscopies performed on patients aged at least 15 years using Current Procedural Terminology (CPT) codes. Each CPT code was designated as a high- or low-complexity procedure, with the former typically requiring accessory incisions or increased operative time. Deep infections were identified by a CPT code for incision and drainage within 90 days of surgery. Superficial infections were identified by International Classification of Diseases, Ninth Revision infection codes without any record of incision and drainage. Patients were compared based on age, sex, body mass index, tobacco use, presence of diabetes, and Charlson Comorbidity Index. RESULTS: A total of 526,537 patients underwent 595,083 arthroscopic knee procedures. Deep postoperative infections occurred at a rate of 0.22%. Superficial infections occurred at a rate of 0.29%. Tobacco use and morbid obesity were the largest risk factors for deep and superficial infections, respectively (P < .001; relative risk of 1.90 and 2.19, respectively). There were also higher infection rates among patients undergoing relatively high-complexity arthroscopies, men, obese patients, diabetic patients, and younger patients (in order of decreasing relative risk). Increased Charlson Comorbidity Index was associated with superficial and total infections (P < .001). CONCLUSIONS: Post arthroscopic knee infections were more frequent among morbidly obese patients, tobacco users, patients undergoing relatively complex procedures, men, obese patients, diabetic patients, relatively young patients, and patients with increased comorbidity burdens in this study population. This knowledge may allow more informed preoperative counseling, aid surgeons in patient selection, and facilitate infection prevention by targeting individuals with higher inherent risk. LEVEL OF EVIDENCE: Level IV, cross-sectional study. PMID- 27407028 TI - Hyaline globules and papillary fragments in cytologic smears from two intra abdominal tumors (ovarian and hepatic) in female patients: A diagnostic pitfall with histologic correlation. AB - Hyaline globules and papillary fragments in cytologic samples from two intra abdominal tumors in young females are presented including the cytological features and the correlation with the histopathologic and immunohistochemical findings. In the first case a cytologic study from an ovarian mass showed papillary structures and isolated tumor cells with epithelioid morphology, irregular reniform-like nuclear contour, pale or vacuolated cytoplasm, abundant hyaline globules and occasional glomeruloid structures resembling Schiller-Duval bodies. Yolk sac tumor (YST) was the diagnosis on the histological slides. Tumor cells showed positivity for cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), alpha-fetoprotein (AFP) and Sal-like protein 4 (SALL4). In case number two the cytologic study from a liver metastasis displayed papillary and rosette-like clusters composed of uniform and bland cells showing occasional long cytoplasmic tails, hyaline globules and nuclear grooves. A diagnosis of hepatic metastasis from solid pseudopapillary neoplasm of the pancreas (SPNP) was rendered from the histology. Tumor cells revealed immunoreactivity for cytokeratin (AE1/AE3), Vimentin, Galectin-1 (GAL-1), Neuron specific-enolase, CD10, progesterone and beta-catenin (nuclear stain). Regarding differential diagnosis, in the patient with the ovarian mass an ovarian clear cell carcinoma was considered, as well as other germ cell tumors or metastatic carcinoma, while in the patient with a liver metastasis a neuroendocrine carcinoma was taken into account. YST and SPNP share some cytological findings, including hyaline globules, papillary structures, clear cells and intercellular eosinophilic basement membrane deposits. Thus, a detailed study and careful interpretation of the cytological, histological and immunohistochemical findings may be worthwhile to avoid a potential misdiagnosis, particularly in the cytologic specimens of the ovarian and/or intra-abdominal mass, when involving young females. Diagn. Cytopathol. 2016;44:935-943. (c) 2016 Wiley Periodicals, Inc. PMID- 27407030 TI - Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles. AB - Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We describe the design and synthesis of novel SERM type ligands based on the 2 arylindole scaffold to selectively target the estrogen receptor in hormone dependent breast cancers. Some of these novel compounds are designed as bisindole type structures, while others are conjugated to a cytotoxic agent based on combretastatin A4 (CA4) which is a potent inhibitor of tubulin polymerisation. The indole compounds synthesised within this project such as 31 and 86 demonstrate estrogen receptor (ER) binding and strong antiproliferative activity in the ER positive MCF-7 breast cancer cell line with IC50 values of 2.71MUM and 1.86MUM respectively. These active compounds induce apoptotic activity in MCF-7 cells with minimal effects on normal peripheral blood cells. Their strong anti cancer effect is likely mediated by the presence of two ER binding ligands for 31 and an ER binding ligand combined with a cytotoxic agent for 86. PMID- 27407029 TI - A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds. AB - Members of arachnida, such as spiders and scorpions, commonly produce venom with specialized venom glands, paralyzing their prey with neurotoxins that specifically target ion channels. Two well-studied motifs, the disulfide-directed hairpin (DDH) and the inhibitor cystine knot motif (ICK), are both found in scorpion and spider toxins. As arachnids, ticks inject a neurotoxin-containing cocktail from their salivary glands into the host to acquire a blood meal, but peptide toxins acting on ion channels have not been observed in ticks. Here, a new neurotoxin (ISTX-I) that acts on sodium channels was identified from the hard tick Ixodes scapularis and characterized. ISTX-I exhibits a potent inhibitory function with an IC50 of 1.6 MUM for sodium channel Nav1.7 but not other sodium channel subtypes. ISTX-I adopts a novel structural fold and is distinct from the canonical ICK motif. Analysis of the ISTX-I, DDH and ICK motifs reveals that the new ISTX-I motif might be an intermediate scaffold between DDH and ICK, and ISTX I is a clue to the evolutionary link between the DDH and ICK motifs. These results provide a glimpse into the convergent evolution of neurotoxins from predatory and blood-sucking arthropods. PMID- 27407031 TI - Synthesis and biological evaluation of 3-substituted 5-benzylidene-1-methyl-2 thiohydantoins as potent NADPH oxidase (NOX) inhibitors. AB - We report the synthesis of novel 3-substituted 5-benzylidene-1-methyl-2 thiohydantoins 3, and their biological evaluation using NADPH oxidase (NOX) 1 and 4. Based on structural and pharmacophore analyses of known inhibitors such as hydroxypyrazole 2, we envisioned interesting 2-thiohydantoin compounds, 3 substituted 5-benzylidene-1-methyl-2-thiohydantoins 3 that would be expected to well match the structural features in 2. Efficient synthesis of eighteen target compounds 3 were achieved through the synthetic pathway of 4->11->3, established after consideration of several plausible synthetic pathways. The inhibitory activities of compounds 3 against NOX 1 and 4 were measured, with some of the target compounds showing similar or higher activities compared with reference 2; in particular, compounds 3bz, 3cz, and 3ez were found to be promising inhibitors of both NOX 1 and 4 with modest isozyme selectivities, which highlights the significance of the 2-thiohydantoin substructure for inhibition of NOX 1 and 4. This marks the first time these compounds have been applied to the inhibition of NOX enzymes. PMID- 27407032 TI - Design, synthesis, and evaluation of Trolox-conjugated amyloid-beta C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer's disease. AB - Two hallmarks of Alzheimer's disease (AD) observed in the brains of patients with the disease include oxidative injury and deposition of protein aggregates comprised of amyloid-beta (Abeta) variants. To inhibit these toxic processes, we synthesized antioxidant-conjugated peptides comprised of Trolox and various C terminal motifs of Abeta variants, TxAbetax-n (x=34, 36, 38, 40; n=40, 42, 43). Most of these compounds were found to exhibit anti-aggregation activities. Among them, TxAbeta36-42 significantly inhibited Abeta1-42 aggregation, showed potent antioxidant activity, and protected SH-SY5Y cells from Abeta1-42-induced cytotoxicity. Thus, this method represents a promising strategy for developing multifunctional AD therapeutic agents. PMID- 27407033 TI - Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo(RLsKDK) for the treatment of inflammatory diseases and cancer metastasis. AB - The metalloproteinase ADAM8 serves as a pivotal catalyst in the development of inflammatory diseases and cancer metastasis. The cyclic peptide cyclo(RLsKDK) has been shown to inhibit the enzymatic activity of ADAM8 with high specificity and potency. Herein we report a structure-activity relationship (SAR) study of cyclo(RLsKDK) that involves the synthesis and biological evaluation of the lead compound and structural analogues thereof. This study provides insight into the ligand-receptor interactions that govern the binding of cyclo(RLsKDK) to the ADAM8 disintegrin domain and represents a stepping stone for the development of new treatments for inflammatory diseases and cancer metastasis. PMID- 27407034 TI - Searching events in AFM force-extension curves: A wavelet approach. AB - An algorithm, based on the wavelet scalogram energy, for automatically detecting events in force-extension AFM force spectroscopy experiments is introduced. The events to be detected are characterized by a discontinuity in the signal. It is shown how the wavelet scalogram energy has different decay rates at different points depending on the degree of regularity of the signal, showing faster decay rates at regular points and slower rates at singular points (jumps). It is shown that these differences produce peaks in the scalogram energy plot at the event points. Finally, the algorithm is illustrated in a tether analysis experiment by using it for the detection of events in the AFM force-extension curves susceptible to being considered tethers. Microsc. Res. Tech. 80:153-159, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27407035 TI - Cobalt oxide nanosheets wrapped onto nickel foam for non-enzymatic detection of glucose. AB - Ultra-sensitive and highly selective detection of glucose is essential for the clinical diagnosis of diabetes. In this paper, an ultra-sensitive glucose sensor was successfully fabricated based on cobalt oxide (Co3O4) nanosheets directly grown on nickel foam through a simple hydrothermal method. Characterizations indicated that the Co3O4 nanosheets are completely and uniformly wrapped onto the surface of nickel foam to form a three-dimensional heterostructure. The resulting self-standing electrochemical electrode presents a high performance for the non enzymatic detection of glucose, including short response time (<10 s), ultra sensitivity (12.97 mA mM(-1) cm(-2)), excellent selectivity and low detection limit (0.058 MUM, S/N = 3). These results indicate that Co3O4 nanosheets wrapped onto nickel foam are a low-cost, practical, and high performance electrochemical electrode for bio sensing. PMID- 27407036 TI - Oncolytic Viruses: Therapeutics With an Identity Crisis. AB - Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms. PMID- 27407037 TI - Use of Locking Plate and Strut Onlay Allografts for Periprosthetic Fracture Around Well-Fixed Femoral Components. AB - BACKGROUND: The purpose of this study was to determine: validated clinical and radiographic outcomes of periprosthetic femoral fractures around stable hip implants treated with plate fixation and additional cortical strut onlay allografts without revision of the stem; radiographic signs of fracture healing; allograft-to-host bone union; resorption of cortical strut allograft; and frequency of complications. METHODS: At our institute, 24 patients (25 hips) were identified with Vancouver type B1 fracture at the tip of the femoral stem and one patient (one hip) was identified with a Vancouver type C fracture of the femur. All these fractures were treated with combined use of locking plate fixation and cortical strut onlay allografts. There were 18 women and 7 men, with an average age of 63 years. Harris hip score and University of California, Los Angeles activity score were used to assess postoperative function. The average duration of follow-up was 3.7 years (range, 1-7 years). RESULTS: Harris hip score at final review was 86 points (range, 65-95 points). University of California, Los Angele activity score averaged 5.8 +/- 1.3 point (range, 3.5-10 points) at final follow up. All but 2 patients returned to their preoperative functional level within 1 year. Twenty-three of 26 hips had fracture union following the first operation. Three hips were failed to obtain fixation because of insufficient length of plate and allograft. Cortical strut onlay allografts were incorporated in the host femur in all hips by one year. Minor resorption of allograft was noticed, but there was no failure of any of the cortical strut allografts. CONCLUSION: The cortical strut onlay allografts facilitated the mechanical stability and the biological fracture healing in addition to plate fixation. PMID- 27407038 TI - Adiposity among 132 479 UK Biobank participants; contribution of sugar intake vs other macronutrients. AB - Background: Policy makers are being encouraged to specifically target sugar intake in order to combat obesity. We examined the extent to which sugar, relative to other macronutrients, was associated with adiposity. Methods: We used baseline data from UK Biobank to examine the associations between energy intake (total and individual macronutrients) and adiposity [body mass index (BMI), percentage body fat and waist circumference]. Linear regression models were conducted univariately and adjusted for age, sex, ethnicity and physical activity. Results: Among 132 479 participants, 66.3% of men and 51.8% of women were overweight/obese. There was a weak correlation (r = 0.24) between energy from sugar and fat; 13% of those in the highest quintile for sugar were in the lowest for fat, and vice versa. Compared with normal BMI, obese participants had 11.5% higher total energy intake and 14.6%, 13.8%, 9.5% and 4.7% higher intake from fat, protein, starch and sugar, respectively. Hence, the proportion of energy derived from fat was higher (34.3% vs 33.4%, P < 0.001) but from sugar was lower (22.0% vs 23.4%, P < 0.001). BMI was more strongly associated with total energy [coefficient 2.47, 95% confidence interval (CI) 2.36-2.55] and energy from fat (coefficient 1.96, 95% CI 1.91-2.06) than sugar (coefficient 0.48, 95% CI 0.41-0.55). The latter became negative after adjustment for total energy. Conclusions: Fat is the largest contributor to overall energy. The proportion of energy from fat in the diet, but not sugar, is higher among overweight/obese individuals. Focusing public health messages on sugar may mislead on the need to reduce fat and overall energy consumption. PMID- 27407039 TI - Psychiatric comorbidity in autism spectrum disorder: Correspondence between mental health clinician report and structured parent interview. AB - Publicly funded mental health services are critical in caring for children with autism spectrum disorder. Accurate identification of psychiatric comorbidity is necessary for effective mental health treatment. Little is known about psychiatric diagnosis for this population in routine mental health care. This study (1) examined correspondence between psychiatric diagnoses reported by mental health clinicians and those derived from a structured diagnostic interview and (2) identified predictors of agreement between clinician-reported and diagnostic interview-derived diagnoses in a sample of 197 children aged 4-14 years with autism spectrum disorder receiving mental health services. Data were drawn from a randomized effectiveness trial conducted in publicly funded mental health services. Non-autism spectrum disorder diagnoses were assessed using an adapted version of the Mini-International Neuropsychiatric Interview, parent version. Cohen's kappa was calculated to examine agreement between Mini International Neuropsychiatric Interview, parent version and clinician-reported diagnoses of comorbid conditions. Children met criteria for an average of 2.83 (standard deviation = 1.92) Mini-International Neuropsychiatric Interview, parent version diagnoses. Agreement was poor across all diagnostic categories (kappa values: 0.06-0.18). Logistic regression identified child gender and clinical characteristics as significant predictors of agreement for specific diagnoses. Results underscore the need for training mental health clinicians in targeted assessment of specific psychiatric disorders and prioritizing treatment development and testing for specific diagnoses to improve care for children with autism spectrum disorder served in publicly funded mental health settings. PMID- 27407041 TI - Social media: Standardized hashtags in #gastroenterology. PMID- 27407040 TI - Self-regulation and quality of life in high-functioning young adults with autism. AB - BACKGROUND: Autism is generally associated with poor functional outcome but little is known about predictors of quality of life, especially during early adulthood. This study was conducted to assess subjective quality of life during early adulthood in high-functioning autism spectrum disorder and its relation with self-regulating abilities. Individuals with high-functioning autism spectrum disorder who progressed into post-secondary higher education ( N = 75) were compared to a typical peer control group ( N = 28) based on behavioral self report questionnaires. The results indicated that individuals with high functioning autism spectrum disorder reported significantly lower subjective quality of life than typical controls ( p < 0.001, effect size ( d) = 1.84). In addition, individuals with high-functioning autism spectrum disorder reported more problems with emotion processing ( p < 0.05, effect size ( d) = 0.79) and daily executive functioning ( p < 0.001, effect size ( d) = 1.29) than controls. A higher level of executive functioning problems was related to lower quality of life in the high-functioning autism spectrum disorder group, but no significant relation between level of emotion processing and subjective quality of life became apparent in the regression analysis. Our findings show that even in high functioning young adults with autism, executive functioning, emotion processing, and subjective quality of life are low compared to typically developing peers. Furthermore, these results emphasize the importance of targeting executive functioning problems in individuals with autism to improve subjective quality of life. PMID- 27407042 TI - IBD: Treatment for acute severe ulcerative colitis. PMID- 27407043 TI - Diagnosis: Rome IV criteria for FGIDs - an improvement or more of the same? PMID- 27407044 TI - Intestinal tract: Sentinel goblet cells flush out bacteria from crypts. PMID- 27407045 TI - NAFLD: Severity of NAFLD in patients who are not obese. PMID- 27407046 TI - GERD: A challenge to our view of reflux oesophagitis pathogenesis. PMID- 27407047 TI - Liver: Novel therapeutic strategy for Wilson disease. PMID- 27407048 TI - Illuminating the dual-hormone hypothesis: About chronic dominance and the interaction of cortisol and testosterone. AB - The dual-hormone hypothesis suggests that testosterone is positively associated with status-seeking tendencies such as aggression and dominance, particularly in individuals with low levels of cortisol. Although recent research supports the dual-hormone hypothesis, its boundary conditions under which the dual-hormone interaction is likely to emerge are not clearly understood. In the present study (N = 153), the dual-hormone hypothesis was empirically tested in the context of an economic game that included a decision whether to dominate another individual. We also examined whether the dual-hormone interaction is more likely to be found in individuals who are chronically prone to dominance tendencies. Results revealed a significant testosterone * cortisol interaction in line with the dual hormone hypothesis. Additionally, the testosterone * cortisol interaction was only significant in individuals with a high level of chronic dominance. Overall, the present work suggests that chronic personality tendencies should be taken into account in order to explore (the boundary conditions) of hormone-behavior associations. Aggr. Behav. 43:85-92, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27407049 TI - Short-term risk of liver and renal injury in hospitalized patients using micafungin: a multicentre cohort study. AB - BACKGROUND: Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice. METHODS: MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis. RESULTS: There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators. CONCLUSION: For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. PMID- 27407050 TI - A Bullous Flare of a Hyperkeratotic Affair: A Case Report. AB - BACKGROUND: Darier's disease is an autosomal dominant genodermatosis typified by hyperkeratotic papules and plaques in a predominately seborrheic distribution. The vesiculo-bullous variant of Darier's disease is rare. Several previously reported cases have demonstrated clinical and microscopic features resembling familial benign chronic pemphigus or Hailey-Hailey disease. OBJECTIVES: The objective of this report is to describe an uncommon presentation of Darier's disease, which has been infrequently described in the literature. METHODS: The authors present a case of bullous flare of long-standing Darier's disease. CONCLUSIONS: Darier's disease may assume several atypical morphologies, including vesiculo-bullous lesions. PMID- 27407051 TI - Niacin: Time to Believe Outcomes Over Surrogate Outcomes: If Not Now, When? PMID- 27407052 TI - Derivation and Validation of Prognosis-Based Age Cutoffs to Define Elderly in Cardiac Surgery. AB - BACKGROUND: The age cutoff to define elderly is controversial in cardiac surgery, empirically ranging from >=65 to >=80 years. Beyond semantics, this has important implications as a starting point for clinical care pathways and inclusion in trials. We sought to characterize the relationship between age and adverse outcomes in patients undergoing cardiac surgery and to derive and validate prognosis-based age cutoffs. METHODS AND RESULTS: Six thousand five hundred seventy one consecutive adult patients undergoing cardiac surgery at 3 hospitals in the United States and Canada were included in the cohort. Logistic regression models and generalized additive models with thin-plate splines were fit to the data. The age distribution was 50 to 59 years in 1244 (18.9%), 60 to 69 years in 2144 (32.6%), 70 to 79 years in 2000 (30.4%), >=80 years in 1183 (18.0%) patients. After controlling for sex and type of operation, the relationship between age and 30-day operative mortality was found to be nonlinear. Receiver operating characteristic analysis showed that the optimal cutoffs to identify older patients at higher risk of operative mortality were greater than 74, 78, and 75 years for isolated coronary bypass, isolated valve surgery, and coronary bypass plus valve surgery, respectively. These age cutoffs were validated in an independent cohort. CONCLUSIONS: The relationship between age and operative mortality is not linear, manifesting a steeper rise after age 75 for coronary bypass and approaching octogenarian age for isolated valve surgery. Rather than using arbitrary age cutoffs to define elderly, the outcomes-based cutoff of >=75 years should be used to identify the population of older adults that has higher risk and may benefit from preoperative geriatric evaluation and optimization. PMID- 27407054 TI - National Survey of UK Consultant Surgeons' Opinions on Surgeon-Specific Mortality Data in Cardiothoracic Surgery. AB - BACKGROUND: In the United Kingdom, cardiothoracic surgeons have led the outcome reporting revolution seen over the last 20 years. The objective of this survey was to assess cardiothoracic surgeons' opinions on the topic, with the aim of guiding future debate and policy making for all subspecialties. METHODS AND RESULTS: A questionnaire was developed using interviews with experts in the field. In January 2015, the survey was sent out to all consultant cardiothoracic surgeons in the United Kingdom (n=361). Logistic regression, bivariate correlation, and the chi(2) test were used to assess whether there was a relationship between answers and demographic variables. Free-text responses were analyzed using the grounded theory approach. The response rate was 73% (n=264). The majority of respondents (58.1% oppose, 34.1% favor, and 7.8% neither) oppose the public release of surgeon-specific mortality data and associate it with several adverse consequences. These include risk-averse behavior, gaming of data, and misinterpretation of data by the public. Despite this, the majority overwhelmingly supports publication of team-based measures of outcome. The free text responses suggest that this is because most believe that quality of care is multifactorial and not represented by an individual's mortality rate. CONCLUSIONS: There is evident opposition to surgeon-specific mortality data among UK cardiothoracic surgeons who associate this with several unintended consequences. Policy makers should refine their strategy behind publication of surgeon-specific mortality data and possibly consider shift toward team-based results for which there will be the required support. Stakeholder feedback and inclusive strategy should be completed before introducing major initiatives to avoid unforeseen consequences and disagreements. PMID- 27407055 TI - Effectiveness of Left Atrial Appendage Exclusion Procedures to Reduce the Risk of Stroke: A Systematic Review of the Evidence. AB - BACKGROUND: Atrial fibrillation is an important cause of cardioembolic stroke. Oral anticoagulants (OAC) reduce stroke risk but increase the risk of serious bleeding. Left atrial appendage (LAA) procedures have been developed to isolate the LAA from circulating blood flow, as an alternative to OAC. We conducted a systematic review of the benefits and harms of surgical and percutaneous LAA exclusion procedures. METHODS AND RESULTS: We searched multiple data sources, including Ovid MEDLINE, Cochrane, and Embase, through January 7, 2015. Of 2567 citations, 20 primary studies met prespecified inclusion criteria. We abstracted data on patient characteristics, stroke, mortality, and adverse effects. We assessed study quality and graded the strength of evidence using published criteria. Trials found low-strength evidence that percutaneous LAA exclusion confers similar risks of stroke and mortality as continued OAC, but this evidence was limited to the Watchman device in patients eligible for long-term OAC. Observational studies found moderate-strength evidence of serious harms with a variety of percutaneous LAA procedures. There is low-strength evidence that surgical LAA exclusion does not add significant harm during heart surgery for another indication, but evidence on stroke reduction is insufficient. CONCLUSIONS: There is limited evidence that the Watchman device may be noninferior to long-term OAC in selected patients. Data on effectiveness of LAA exclusion devices is lacking in patients ineligible for long-term OAC. Percutaneous LAA devices are associated with high rates of procedure-related harms. Although surgical LAA exclusion during heart surgery does not seem to add incremental harm, there is insufficient evidence of benefit. PMID- 27407053 TI - Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs. AB - BACKGROUND: Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown. METHODS AND RESULTS: 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK L; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK L101 [SE L37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs. CONCLUSIONS: In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin based therapy reduced quality of life-adjusted survival and increased hospital costs. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00461630. PMID- 27407056 TI - Fostering a Culture to Support Surgical Outcome Measures. PMID- 27407057 TI - Averted health burden over 4 years at Medecins Sans Frontieres (MSF) Trauma Centre in Kunduz, Afghanistan, prior to its closure in 2015. AB - BACKGROUND: On October 3, 2015, a United States airstrike hit Medecins Sans Frontieres (Doctors Without Borders) Trauma Centre in Kunduz, Afghanistan. Our aim was to describe the care provided and estimate the health burden averted by surgical care at the hospital. We also report the benefit rendered by the Trauma Centre to the health of the local population prior to its destruction. METHODS: All operations performed in an operating theater at the Trauma Centre from its opening on August 30, 2011, to August 31, 2015, were described. Disability adjusted life years averted by operative care over the same period were estimated. RESULTS: The Trauma Centre performed 13,970 operations, which included 17,928 procedures for 6,685 patients. The median age of patients who required operative intervention was 21 years (interquartile range 12-34 years). More than 85% of patients were men (12,034 patients; 86%). Of the 6,685 patients who required operative care, 4,387 suffered unintentional, non-violence-related injuries (66%), while 2,276 suffered violence-related injuries (34%). The perioperative death rate at the facility decreased from 7.2 deaths per 1,000 operations in 2011 to 1.3 deaths in 2015 (P = .03). More than 154,250 disability adjusted life years were averted by operative care (95% confidence interval 153,042-155,465). CONCLUSION: The health burden averted by the surgical care provided at the Trauma Centre was large; it is critically felt by those still living in the region. Access to essential trauma care for all victims of armed conflict is a human right; as directed by International Humanitarian Law, we must guarantee special protection for the wounded, sick, and medical personnel and facilities during war. PMID- 27407059 TI - Cognitive-behavioural treatment for depression in Alzheimer's disease patients: a case study. PMID- 27407058 TI - Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma. AB - BACKGROUND: Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response >=6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma. RESULTS: DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec. CONCLUSION: Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016. PMID- 27407060 TI - Examining hospice enrollment through a novel lens: Decision time. AB - OBJECTIVE: No prior studies on hospice utilization have captured information about the amount of time between when one first learns of hospice as a potential option for care and when he/she actually enrolls. Little is in fact known about this decision-making process. The present study examines hospice enrollment by exploring relationships between hospice decision time and known barriers to care. METHOD: This was an exploratory cross-sectional study. Pearson's r was employed to identify bivariate relationships between barriers to care and decision time for hospice care. Independent-sample t tests and ANOVA were utilized to consider differences in decision time across key variables. RESULTS: Some 90 hospice patients, or their primary decision maker, participated in the study from a not for-profit hospice located in the southern United States. Decision time was correlated with referral source, use of disease-directed treatment, functional status (on the Palliative Performance Scale [PPS]), age, diagnosis, income, race, and spirituality-suggesting that decision time is a pertinent variable when examining hospice utilization. Differences in decision time were found across diagnosis, race, income, and referral source. SIGNIFICANCE OF RESULTS: This study provides implications for policy and practice, particularly for clinicians faced with initial conversations about hospice care. Differences in decision time highlight ongoing needs related to overcoming healthcare disparities, the important role of including families in initial conversations, and the potential need for varied approaches to talking about hospice care based upon diagnosis. Results also highlight the need for policies supportive of concurrent care, where hospice can be accessed alongside curative care. PMID- 27407061 TI - Altered recovery from inhibitory repetitive transcranial magnetic stimulation (rTMS) in subjects with photosensitive epilepsy. AB - OBJECTIVE: To investigate functional changes underlying photosensitivity, we studied the response of the visual cortex to low-frequency, inhibitory repetitive transcranial magnetic stimulation (rTMS) in drug-free patients with photosensitive seizures and healthy volunteers. METHODS: Visual evoked potentials (VEPs) triggered by grating stimuli of different contrasts were recorded in both hemispheres before and after transient functional inactivation of the occipital cortex of one side via low-frequency rTMS (0.5Hz for 20'). VEPs were recorded before (T0), immediately after (T1) and 45' following the completion of rTMS (T2). RESULTS: Baseline amplitudes of the early VEP components (N1 and P1) were enhanced in photosensitive patients. At T1, rTMS produced an inhibitory effect on VEPs amplitudes at all contrasts in the targeted side and a concurrent facilitation of responses in the contralateral hemisphere. Compared with PSE subjects, VEP amplitudes remained persistently dampened in the stimulated hemisphere of controls (Holm-Sidak post-hoc method, p<0.05). In the contralateral hemisphere, we found a clear enhancement of VEP amplitude in photosensitive subjects but not controls at T2 (Holm-Sidak test, p<0.001). CONCLUSIONS: Visual responses recovered more quickly in the stimulated hemisphere, and disinhibition persisted in the contralateral side of photosensitive subjects. SIGNIFICANCE: The rapid recovery of excitability and the persistent transcallosal disinhibition following perturbation of cortical activity may play a role in the pathophysiology of photosensitive epilepsy. PMID- 27407062 TI - Authors' Response. PMID- 27407063 TI - Mantle cell lymphoma-variant Richter syndrome: Detailed molecular-cytogenetic and backtracking analysis reveals slow evolution of a pre-MCL clone in parallel with CLL over several years. AB - Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-based second-line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole-exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of ATM gene or emergence of TP53, CREBBP, NUP214, FUBP1 and SF3B1 gene mutations. Similarly, gene expression analysis revealed vast differences between the MCL and CLL transcriptome, including overexpression of cyclin D1, downregulation of cyclins D2 and D3, or downregulation of IL4R in the MCL clone. Backtracking analysis using quantitative PCR specifically detecting an MCL-restricted focal deletion of TP53 revealed that the pre-MCL clone appeared in the bone marrow and peripheral blood of the patient approximately 4 years before the clinical manifestation of MCL. Both molecular cytogenetic and sequencing data support the hypothesis of a slow development of the pre-MCL clone in parallel to CLL over several years, and thereby exclude the possibility that the transformation event occurred at the stage of the CLL relapse clone by mere t(11;14)(q13;q32) acquisition. PMID- 27407064 TI - Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease. AB - Neprilysin (NEP) is the most important Abeta-degrading enzyme. Its expression level decreases with age and inversely correlated with amyloid accumulation, suggesting its correlation with the late-onset of Alzheimer's disease. Recently, many reports showed that upregulating NEP level is a promising strategy in the prevention and therapy of Alzheimer's disease. Here, we used a sensitive fluorescence-based Abeta digestion assay to screen 25 curcumin analogs for their ability to upregulate NEP activity. To our surprise, four compounds, dihydroxylated curcumin, monohydroxylated demethoxycurcumin, and mono- and di hydroxylated bisdemethoxycurcumin, increased NEP activity, while curcumin did not. The ability of these polyhydroxycurcuminoids to upregulate NEP was further confirmed by mRNA and protein expression levels in the cell and mouse models. Finally, feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Abeta accumulation in the hippocampus and cortex. These polyhydroxycurcuminoids offer hope in the prevention of Alzheimer's disease. PMID- 27407065 TI - The identification and evaluation of two different color variations of tea. AB - BACKGROUND: The tea plant, Camellia sinensis (L.) O. Kuntz, is a perennial woody plant widely cultivated for the production of a popular non-alcoholic beverage. To rapidly identify and evaluate two different color tea varieties (yellowish and purplish), the main phenotypic traits and quality components were tested in the present study. The metabolic profiles of tea shoots and leaves were also analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: The yellowish variation had a higher active level with respect to metabolism of catechins, and the contents of luteolin and kaempferol 3-alpha-d-glucoside were much higher compared to in the other variations. However, the purplish variation had a low content of theanine and a high content of caffeine. The contents of quercetin and kaempferol 3-alpha-d-galactoside were highest in purplish leaves. Moreover, the yellowish variation had the highest total quality scores for green teas and black teas, whereas the purplish variation had the highest scores for oolong teas. CONCLUSION: Both the yellowish variation and the purplish variation represent excellent breeding materials and are worthy of breeding as new tea cultivars. The yellowish variation is more suitable for making high-grade green teas or black teas, whereas the purplish variation is suitable for producing fine quality oolong teas. (c) 2016 Society of Chemical Industry. PMID- 27407066 TI - Pap-tests with non-hyperchromatic dyskariosis are often associated with squamous intraepithelial lesions of the cervix uteri with eosinophilic features. AB - BACKGROUND: Squamous intraepithelial lesions of the cervix uteri with eosinophilic features (eosinophilic dysplasia, ED) are a peculiar type of dysplasia with metaplastic phenotype which was described in histological specimens. The cytological features of these lesions have not been studied yet. METHODS: Histological samples from 66 women with features of ED and positive p16(INK4a) staining were included in the study. Within the previous year, all women had at least one pap-test, whose features were recorded and compared with 31 control samples with high-grade dysplasia of usual type. RESULTS: The previous pap-test showed high-grade dysplastic cells with non-hyperchromatic nuclei in 56/66 (84.8%) cases and metaplastic features in 60/66 (90.9%) cases. Conversely, the dysplastic cells of the usual lesions showed non-hyperchromatic nuclei in 6/31 (19.4%) and metaplastic features in 4/31 (12.9%) cases. Statistical analysis showed significant differences in distribution of the non-hyperchromatic nuclei (P < 0.001), metaplastic features (P < 0.001), presence of both non hyperchromatic nuclei and metaplastic features (P < 0.001) and usual dysplastic features (P < 0.001) among the study and control groups. CONCLUSIONS: A high grade squamous intraepithelial lesion with non-hyperchromatic nuclei or metaplastic features is often found in the pap-test previous to the histological diagnosis of ED and may represent the cytologic correlate of this particular type of dysplasia. Diagn. Cytopathol. 2016;44:783-786. (c) 2016 Wiley Periodicals, Inc. PMID- 27407067 TI - Enhancement of the Catalytic Activity of Chiral H8 -BINOL Titanium Complexes by Introduction of Sterically Demanding Groups at the 3-Position. AB - The activity of chiral titanium catalysts derived from H8 -BINOL ligands in the enantioselective arylation of an aldehyde with PhTi(OiPr)3 is significantly enhanced by an increase of the size of the substituent at the 3-position. High enantioselectivity (> 90 % ee) can be obtained even at a substrate/catalyst ratio (S/C) of 800 for DTBP-H8 -BINOL (DTBP=3,5-di-tert-butylphenyl) and DAP-H8 -BINOL (DAP=3,5-di(9-anthraceny)phenyl). These titanium catalysts are successfully applied to the enantioselective arylation and heteroarylation of aldehydes at a S/C ratio of 400 by using organotitanium reagents generated in situ from bromide precursors. The remarkable weakening of the intramolecular aggregation of the two -Ti(OiPr)3 units in a DPP-H8 -BINOL (DPP=3,5-diphenylpheny)-derived bis-titanium complex is revealed by X-ray and variable-temperature (VT)-NMR studies. Based on these observations, a catalytic cycle, involving the rate-limiting aryl group transfer followed by aldehyde complexation and enantioselective arylation, is proposed to account for the high activity of the 3-substituted H8 -BINOL catalyst system. PMID- 27407068 TI - Three-dimensional protein assemblies directed by orthogonal non-covalent interactions. AB - In this report, an orthogonal non-covalent interaction strategy based on specific recognition between sugar and protein, and host-guest interaction, was employed to construct artificial three dimensional (3D) protein assemblies in the laboratory. PMID- 27407069 TI - Biophysical signalling from and to the (stem) cells: a novel path to regenerative medicine. PMID- 27407070 TI - Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study. AB - Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases. PMID- 27407071 TI - Long-Term Outcomes From Acute Rheumatic Fever and Rheumatic Heart Disease: A Data Linkage and Survival Analysis Approach. AB - BACKGROUND: We investigated adverse outcomes for people with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) and the effect of comorbidities and demographic factors on these outcomes. METHODS: Using linked data (RHD register, hospital, and mortality data) for residents of the Northern Territory of Australia, we calculated ARF recurrence rates, rates of progression from ARF to RHD to severe RHD, RHD complication rates (heart failure, endocarditis, stroke, and atrial fibrillation), and mortality rates for 572 individuals diagnosed with ARF and 1248 with RHD in 1997 to 2013 (94.9% Indigenous). RESULTS: ARF recurrence was highest (incidence, 3.7 per 100 person-years) in the first year after the initial ARF episode, but low-level risk persisted for >10 years. Progression to RHD was also highest (incidence, 35.9) in the first year, almost 10 times higher than ARF recurrence. The median age at RHD diagnosis in Indigenous people was young, especially among males (17 years). The development of complications was highest in the first year after RHD diagnosis: heart failure incidence rate per 100 person-years, 9.09; atrial fibrillation, 4.70; endocarditis, 1.00; and stroke, 0.58. Mortality was higher among Indigenous than non-Indigenous RHD patients (hazard ratio, 6.55; 95% confidence interval, 2.45-17.51), of which 28% was explained by comorbid renal failure and hazardous alcohol use. RHD complications and mortality rates were higher for urban than for remote residents. CONCLUSIONS: This study provides important new prognostic information for ARF/RHD. The residual Indigenous survival disparity in RHD patients, which persisted after accounting for comorbidities, suggests that other factors contribute to mortality, warranting further research. PMID- 27407072 TI - Diabetes-Induced Jagged1 Overexpression in Endothelial Cells Causes Retinal Capillary Regression in a Murine Model of Diabetes Mellitus: Insights Into Diabetic Retinopathy. AB - BACKGROUND: Several mechanisms have been proposed to account for diabetes-induced microvasculopathy (DMV). Although Notch signaling was reported to be affected by glucose metabolism in endothelial cells during developmental angiogenesis, it has not been investigated in vascular remodeling of adult capillaries in relation to diabetes mellitus. METHODS: We induced diabetes mellitus in 8-week-old adult mice by intravenously administering streptozotocin. After 6 weeks, we harvested organs, including retina, heart, and skeletal muscle, and evaluated the capillaries with immunofluorescence and confocal microscopy. We modulated endothelial Notch signaling using chemical inhibitors in wild-type mice or transgenic mice, inducing conditional knockout of Jagged1 or Mib1. RESULTS: DMV was characterized by capillary remodeling, regression, and decreased density. Notch ligand Jagged1, but not delta-like ligand 4, was markedly increased in endothelial cells of diabetic mice. Using endothelium-specific Jagged1 knockdown mice, we found that blocking Jagged1 prevented DMV even under diabetic conditions. Furthermore, in the inducible endothelium-specific Jagged1 knockdown mice, blocking Jagged1 even at 4 weeks after the establishment of DMV could reverse it, leading to normalization of retinal vasculature. A search for downstream signals revealed that diabetes mellitus decreased the nuclear localization of Notch1 intracellular domain and reduced the expression of VE cadherin and N-cadherin in endothelial cells. Chemical Notch inhibition phenocopied DMV in normal mice. CONCLUSIONS: Our findings indicate that diabetes mellitus induces Jagged1 overexpression and suppresses Notch signaling in endothelial cells, leading to DMV in adult mice. We conclude that dysregulated intercellular Notch signaling may be a novel mechanism of DMV. PMID- 27407073 TI - School- and Community-Based Youth Suicide Prevention Interventions: Hot Idea, Hot Air, or Sham? AB - Suicide in young people is a significant health concern, with numerous community- and school-based interventions promising to prevent suicide currently being applied across Canada. Before widespread application of any one of these, it is essential to determine its effectiveness and safety. We systematically reviewed the global literature on one of the most common community suicide prevention interventions in Canada and summarized data on 2 commonly applied school-based suicide prevention programmes. None of these has demonstrated effectiveness in preventing youth suicide or safety in application. Concurrently with their widespread distribution in Canada, the suicide rate in young women has increased the first time in over 3 decades. Policy and regulatory implications of these findings are discussed. PMID- 27407074 TI - The Prevalence of Major Depressive Episodes Is Higher in Urban Regions of Canada. AB - OBJECTIVE: Major depressive disorder is an important contributor to disease burden. Anticipation of service needs is important, yet basic information is lacking. For example, there is no consensus as to whether major depressive episodes (MDE) are more or less prevalent in urban or rural areas. The objective of this study was to determine whether a difference exists in Canada. METHOD: A series of 11 Canadian national cross-sectional studies were examined from 2000 to 2014, providing much greater precision than prior analyses. Survey-specific MDE prevalence estimates were synthesized into a pooled odds ratio comparing urban to rural areas using meta-analytic methods. RESULTS: Differences in the survey specific estimates were not in excess of what would be expected due to sampling variability. This suggests that inconsistency in the prior literature is due to inadequate power and precision, an issue addressed by the meta-analytic pooling. The pooled odds ratio for Canada is 1.18 (95% confidence interval, 1.12 to 1.25), indicating that urban regions have higher MDE prevalence than rural regions. However, the difference is very small and of uncertain significance for policy and planning. CONCLUSIONS: Prevalence of MDE is approximately 18% higher in urban compared to rural regions of Canada. The difference is insufficient to impute differing need for services, but the result resolves an inconsistency in the existing literature and may play a role in future needs assessment. PMID- 27407075 TI - Home-based specialized palliative care in patients with advanced cancer: A systematic review. AB - OBJECTIVE: Due to an urgent need for specialized palliative care (SPC) for patients with advanced cancer, an overview of available information on organization and outcomes of home-based SPC would be valuable. Our systematic review aims to give an overview of available information on the organization and outcomes of home-based SPC for patients with advanced cancer. Outcomes related to place of death, survival time, quality of life, performance status, and symptom management are included. METHOD: A PICO process search strategy consisting of terms related to cancer, palliation, and home care was employed. The search was conducted in PubMed, EMBASE, and Cochrane from January 1, 2000, to January 27, 2015. A hand search of the reference lists of the included studies was also performed. RESULTS: A total of 5 articles (out of 2080 abstracts) were selected for analysis. Three additional studies were added by the hand search. Six observational and two interventional studies were evaluated. In all of these studies, the description of the SPC service was limited to the composition of the staff-no other organizational aspects were detailed. From 44 to 90% of the patients receiving home-based SPC died at home. Studies including survival and quality of life had divergent outcomes, and overall performance status did not improve. However, symptom control did improve over time. SIGNIFICANCE OF RESULTS: There is a lack of controlled clinical trials and organizational descriptions regarding home-based SPC for patients with advanced cancer, resulting in poor information and a lack of evidence. Generally, home-based SPC seems to have some positive effect on pain and dyspnea, but more high-quality studies are required. PMID- 27407076 TI - Electrochemical reactivity and proton transport mechanisms in nanostructured ceria. AB - Electrochemical reactivity and ionic transport at the nanoscale are essential in many energy applications. In this study, time-resolved Kelvin probe force microscopy (tr-KPFM) is utilized for surface potential mapping of nanostructured ceria, in both space and time domains. The fundamental mechanisms of proton injection and transport are studied as a function of environmental conditions and the presence or absence of triple phase boundaries. Finite element modeling is used to extract physical parameters from the experimental data, allowing not only quantification of the observed processes, but also decoupling of their contributions to the measured signal. The constructed phase diagrams of the parameters demonstrate a thermally activated proton injection reaction at the triple phase boundary, and two transport processes that are responsible for the low-temperature proton conductivity of nanostructured ceria. PMID- 27407077 TI - Recruitment challenges and strategies: Lessons learned from an early-stage dyadic intervention (innovative practice). AB - An increasing number of family caregivers are seeking services and support due in large part to the dramatic increase in the number of older adults obtaining dementia diagnoses. This paper describes barriers and challenges experienced by our research team in recruiting early-stage dementia caregiving dyads into research studies. Effective recruitment and screening strategies to address these barriers are also discussed. Recruitment and enrollment success depends on these strategies as well as having well-trained recruitment staff who are knowledgeable about the study and have experience working with older adults, and more specifically, persons with dementia. PMID- 27407078 TI - When the path of least resistance is doing everything. PMID- 27407079 TI - TLR7 agonist-induced bronchodilation: key mechanistic questions remain. PMID- 27407080 TI - The bronchodilatory capacity of imiquimod: the existence of two mechanisms. PMID- 27407081 TI - Response to paper by Singh et al. "Hyperinsulinemia adversely affects lung structure and function". PMID- 27407082 TI - Author response to letter to editor: Hyperinsulinemia adversely affects lung structure and function. PMID- 27407083 TI - Tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2, suppresses renal damage in KKAy/Ta mice, obese and type 2 diabetic animals. AB - OBJECTIVE: Inhibitors of sodium-glucose cotransporter 2 ameliorate hyperglycaemia in diabetes by increasing urinary glucose excretion. However, the effects of sodium-glucose cotransporter 2 inhibitors on tubulointerstitial damage in diabetic nephropathy are not fully elucidated. We examined whether tofogliflozin, an inhibitor of sodium-glucose cotransporter 2, suppressed renal damage in KKAy/Ta mice, obese and type 2 diabetic animals. MATERIALS AND METHODS: Male 8 week-old KKAy/Ta mice or control C57BL/6J mice were kept on a standard diet with or without 0.015% tofogliflozin for 5 weeks. Blood glucose and blood pressure, body and kidney weight, urinary N-acetyl-beta-d-glucosaminidase activity and albumin excretion levels were monitored. RESULTS: Although tofogliflozin treatment did not affect blood pressure, body weight or serum creatinine values, it improved hyperglycaemia and blocked the elevation of urinary N-acetyl-beta-d glucosaminidase activity in KKAy/Ta diabetic mice at 9, 11 and 13 weeks. Furthermore, compared with control mice, urinary albumin excretion levels and kidney weight were increased in 13-week-old KKAy/Ta mice, both of which were suppressed by the treatment with tofogliflozin. CONCLUSION: Our present results demonstrated that tofogliflozin could suppress albuminuria and tubulointerstitial injury in obese and type 2 diabetic mice. Inhibition of glucose entry into tubular cells by tofogliflozin may exert renoprotective properties in diabetes. PMID- 27407084 TI - Evaluation of the role of left atrial strain using two-dimensional speckle tracking echocardiography in patients with diabetes mellitus and heart failure with preserved left ventricular ejection fraction. AB - OBJECTIVE: To evaluate additional role of left atrial two-dimensional speckle tracking echocardiography in patients with diabetes mellitus type 2, 218 patients with heart failure with preserved left ventricular ejection fraction divided according to the presence of diabetes mellitus (108 with and 110 without) were enrolled in the study. METHODS: Traditional parameters using two-dimensional echocardiography and Doppler imaging were measured as expressions of left ventricular diastolic function as well as peak atrial longitudinal strain and peak atrial contraction strain were measured using two-dimensional speckle tracking echocardiography. RESULTS: Global average peak atrial longitudinal strain and peak atrial contraction strain were significantly lower in patients with diabetes mellitus (p = 0.002 and p = 0.001, respectively) and its reduced values were significantly associated with higher prevalence of diabetes mellitus (p = 0.002 and p = 0.001, respectively), its greater severity (p = 0.002 and p = 0.016, respectively) and longer duration only for global average peak atrial longitudinal strain (p = 0.030). Multiple linear regression analysis demonstrated that the presence of diabetes mellitus appeared as independent predictor of reduced global peak atrial longitudinal strain [B = -2.173; 95% confidence interval: -3.870 to (-0.477); p = 0.012] as well of reduced global peak atrial contraction strain [B = -1.30; 95% confidence interval: -2.234 to (-0.366); p = 0.007]. CONCLUSION: Two-dimensional speckle tracking echocardiography appeared as a useful additional tool for detection of left atrial dysfunction in patients with heart failure who have preserved left ventricular ejection fraction and diabetes mellitus who are especially prone to develop cardiovascular complications. PMID- 27407085 TI - The Association Between Perceived Stress and Mortality Among People With Multimorbidity: A Prospective Population-Based Cohort Study. AB - Multimorbidity is common and is associated with poor mental health and high mortality. Nevertheless, no studies have evaluated whether mental health may affect the survival of people with multimorbidity. We investigated the association between perceived stress and mortality in people with multimorbidity by following a population-based cohort of 118,410 participants from the Danish National Health Survey 2010 for up to 4 years. Information on perceived stress and lifestyle was obtained from the survey. We assessed multimorbidity using nationwide register data on 39 conditions and identified 4,229 deaths for the 453,648 person-years at risk. Mortality rates rose with increasing levels of stress in a dose-response relationship (P-trend < 0.0001), independently of multimorbidity status. Mortality hazard ratios (highest stress quintile vs. lowest) were 1.51 (95% confidence interval (CI): 1.25, 1.84) among persons without multimorbidity, 1.39 (95% CI: 1.18, 1.64) among those with 2 or 3 conditions, and 1.43 (95% CI: 1.18, 1.73) among those with 4 or more conditions, when adjusted for disease severities, lifestyle, and socioeconomic status. The numbers of excess deaths associated with high stress were 69 among persons without multimorbidity, 128 among those with 2 or 3 conditions, and 255 among those with 4 or more conditions. Our findings suggested that perceived stress contributes significantly to higher mortality rates in a dose-response pattern, and more stress-associated deaths occurred in people with multimorbidity. PMID- 27407086 TI - Accuracy of Palpation-Guided Catheter Placement for Muscle Pressure Measurements in Suspected Deep Posterior Chronic Exertional Compartment Syndrome of the Lower Leg: A Magnetic Resonance Imaging Study. AB - BACKGROUND: A diagnosis of lower leg deep posterior chronic exertional compartment syndrome (dp-CECS) is made by a dynamic pressure measurement. The insertion of a pressure catheter is guided by anatomic landmarks (freehand) or by ultrasound. The catheter tip is ideally positioned in the tibialis posterior muscle (TP). The accuracy of in vivo catheter placement using lower leg magnetic resonance imaging (MRI) in healthy patients suspected of having dp-CECS has never been studied. PURPOSE: To analyze whether a freehand catheter insertion results in accurate positioning in the TP as confirmed by MRI in patients with suspected dp-CECS. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Catheters were inserted into central portions of the TP using a standard puncturing technique guided by lower leg anatomic landmarks. After timed muscle pressure measurements during a standard provocative treadmill running test, lower leg MRI scans were obtained and evaluated by 2 skilled radiologists. Catheter tip placement was termed accurate (in the TP), suboptimal (in the deep posterior compartment but outside the TP), or inaccurate (outside the deep posterior compartment). RESULTS: Between March 2013 and September 2014, a total of 24 patients (8 male, 16 female; mean age, 30 years [range, 18-54 years]) underwent an intracompartmental pressure (ICP) measurement, followed by MRI. Cardinal symptoms were pain during exertion (20% very severe, 53% severe, and 20% moderate) and tightness (29% very severe, 43% severe). Symptoms were bilateral in 74% of patients. Nine of the 24 patients were diagnosed with dp-CECS based on elevated ICPs. Of the 24 patients, catheter tip placement was accurate in 10 (42%), whereas suboptimal placement was achieved in 9 (38%). Five procedures were inaccurate (transition zone between the deep and superficial compartments, n = 3; in the superficial lower leg compartment, n = 2). Signs of a hematoma were found in 38% of the patients, although there were no associated clinical symptoms. CONCLUSION: Palpation-guided placement of catheters for TP pressure measurements is suboptimal in more than half of the patients with suspected lower leg dp-CECS. Optimizing the pressure catheter tip positioning technique may improve diagnostic accuracy in dp-CECS. PMID- 27407087 TI - Medialized Clavicular Bone Tunnel Position Predicts Failure After Anatomic Coracoclavicular Ligament Reconstruction in Young, Active Male Patients. AB - BACKGROUND: Recent radiographic data have suggested that medialized conoid tunnel placement greater than 25% of absolute clavicular length is correlated with early failure after anatomic coracoclavicular ligament reconstructions. A comparison with a larger active duty military cohort of clinical and radiographic outcomes can serve as a basis for standardizing surgical technique. PURPOSE: To establish the ideal radiographic tunnel position for anatomic coracoclavicular ligament reconstruction and to elucidate variables associated with early loss of reduction and ability to return to active-duty military service. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review of the military's electronic medical record between the years 2000 and 2013 was performed. All anatomic coracoclavicular reconstructions at a single institution were included for analysis, and nonanatomic or revision reconstructions were excluded. Radiographic failure was defined as 6 mm of superior clavicle displacement on immediate postoperative films. RESULTS: A cohort of 38 patients underwent 39 anatomic coracoclavicular reconstructions. Average follow-up time was 26 months (range, 1.2-92 months). A total of 20 radiographic failures were identified, with an average conoid tunnel ratio of 0.27. When conoid tunnel ratios were compared with a reference ratio of 0.20 to 0.25, increased risk of failure was statistically significant with lateralization greater than 0.20 (P = .018; odds ratio [OR] = 40 [95% CI, 1.05-999.06]) or with medialization of 0.251 to 0.30 (P = .002; OR = 39 [95% CI, 1.58-944.36]) or greater than 0.30 (P = .029; OR = 21 [95% CI, 0.77-562.15]). Medialization of the trapezoid position greater than 0.16 (vs a range of 0.13-0.16) was also found to be significant for failure (P < .023; OR = 8 [95% CI, 1.33-48.18]). However, these significant findings did not correlate with symptoms or ability to return to duty (P > .05). CONCLUSION: The optimal technique for treating acromioclavicular separations has yet to be determined. Recently, anatomic coracoclavicular reconstruction has demonstrated biomechanical superiority to previously described methods. The findings of optimal tunnel positioning in anatomic reconstructions from this large active duty military cohort can assist preoperative planning to reduce failure rates when treating these difficult injuries. PMID- 27407088 TI - Anatomic Anterolateral Ligament Reconstruction of the Knee Leads to Overconstraint at Any Fixation Angle. AB - BACKGROUND: Anterior cruciate ligament (ACL) tears are one of the most common injuries among athletes. However, the ability to fully restore rotational stability with ACL reconstruction (ACLR) remains a challenge, as evidenced by the persistence of rotational instability in up to 25% of patients after surgery. Advocacy for reconstruction of the anterolateral ligament (ALL) is rapidly increasing because some biomechanical studies have reported that the ALL is a significant contributor to internal rotational stability of the knee. HYPOTHESIS/PURPOSE: The purpose of this study was to assess the effect of ALL reconstruction (ALLR) graft fixation angle on knee joint kinematics in the clinically relevant setting of a concomitant ACLR and to determine the optimal ALLR graft fixation angle. It was hypothesized that all fixation angles would significantly reduce rotational laxity compared with the sectioned ALL state. STUDY DESIGN: Controlled laboratory study. METHODS: Ten nonpaired fresh-frozen human cadaveric knees underwent a full kinematic assessment in each of the following states: (1) intact; (2) anatomic single-bundle (SB) ACLR with intact ALL; (3) anatomic SB ACLR with sectioned ALL; (4) anatomic SB ACLR with 7 anatomic ALLR states using graft fixation angles of 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , and 90 degrees ; and (5) sectioned ACL and ALL. Internal rotation during a 5-N.m internal rotation torque and anterior translation during an 88-N anterior load were recorded at 15 degrees flexion intervals between 0 degrees and 120 degrees . Axial plane translation and internal rotation during a simulated pivot-shift test (combined 5-N.m internal rotation and 10-N.m valgus torques) were recorded between 0 degrees and 60 degrees . Kinematic changes were measured and compared with the intact state for all reconstructed and sectioned states. RESULTS: Anatomic ALLR at all graft fixation angles significantly overconstrained internal rotation of the knee joint beyond 30 degrees of flexion and at 45 degrees and 60 degrees during the pivot shift test. Furthermore, there were no significant knee kinematic differences between any tested graft fixation angles during anterior drawer, pivot-shift, and internal rotation tests. CONCLUSION: Anatomic ALLR in conjunction with an ACLR significantly reduced rotatory laxity of the knee beyond 30 degrees of knee flexion. However, ALLR, regardless of fixation angle, resulted in significant overconstraint of the knee. CLINICAL RELEVANCE: ALLR at any fixation angle overconstrained native joint kinematics and should be performed with careful consideration. Further investigation into the application and target population for ALLR is strongly recommended. PMID- 27407089 TI - FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. AB - On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36-0.59; P < 0.0001]. Safety data confirmed the known adverse reaction profile of palbociclib. The most common adverse reactions (>20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968-72. (c)2016 AACR. PMID- 27407090 TI - Tumor Expression of Vitamin D Receptor and Breast Cancer Histopathological Characteristics and Prognosis. AB - PURPOSE: Our previous work has shown low serum 25-hydroxyvitamin D concentrations in association with aggressive breast cancer subtypes. Vitamin D receptor (VDR) is central for vitamin D-mediated transcription regulation. Few studies have examined breast VDR expression with tumor characteristics or patient survival. EXPERIMENTAL DESIGN: VDR expression in breast tumor tissue microarrays was determined by immunohistochemistry in 1,114 female patients as low, moderate, and strong expression based on an immunoreactive score, and examined with histopathologic tumor characteristics and survival outcomes including progression free survival, breast cancer-specific survival, and overall survival. RESULTS: A majority (58%) of breast tumors showed moderate or strong VDR expression. VDR expression was inversely related to aggressive tumor characteristics, including large tumor size, hormonal receptor (HR) negativity, and triple-negative subtype (P < 0.05). In addition, VDR expression was also inversely related to Ki-67 expression among patients older than 50 years. Nevertheless, VDR expression was not associated with any patient survival outcomes examined. CONCLUSIONS: In a large patient population, VDR expression is inversely associated with more aggressive breast cancer, but not with breast cancer survival outcomes. The present findings of VDR expression are consistent with our previous results of circulating vitamin D biomarkers, which provide two converging lines of evidence supporting the putative benefits of vitamin D against aggressive breast cancer. Because of the observational nature of our analyses, future studies are warranted to establish the causality of the reported associations. Clin Cancer Res; 23(1); 97-103. (c)2016 AACR. PMID- 27407091 TI - Trajectories of Stress, Depressive Symptoms, and Immunity in Cancer Survivors: Diagnosis to 5 Years. AB - PURPOSE: Five-year disease endpoint trajectories are available for every cancer site. In contrast, there are few longitudinal, biobehavioral studies of survivors extending beyond the first or second year following diagnosis. This gap is addressed with stress, depressive symptom, and immunity data from breast cancer patients followed continuously for 5 years. EXPERIMENTAL DESIGN: Women (N = 113) diagnosed and surgically treated for breast cancer and awaiting adjuvant therapy completed self-report measures of stress and depressive symptoms and provided blood for immune assays [natural killer cell cytotoxicity (NKCC) and T-cell blastogenesis]. Assessments (N = 12) were repeated every 4 to 6 months for 5 years. RESULTS: Multiphase linear mixed models show phases of change and identified specific time points of change. Cancer stress shows two distinct phases of decline, with the change point being 12 months. In contrast, a steep decline in depressive symptoms occurs by 7 months, with stable, low levels thereafter. NKCC shows a steady upward trajectory through 18 months and upper limit stability thereafter, whereas there was no reliable trajectory for T-cell blastogenesis. CONCLUSIONS: For the first time, trajectories and specific time points of change in biobehavioral data for breast cancer survivors are provided, traced through 5 years. Following diagnosis, the breast survivor experience is one of a co-occurrence of change (recovery) in psychologic and innate immunity markers from diagnosis to18 months, and a pattern of stability (depression, NKCC) or continued improvement (stress) through year 5. These data provide new directions for survivorship care and detail of the biobehavioral trajectory. Clin Cancer Res; 23(1); 52-61. (c)2016 AACR. PMID- 27407093 TI - Physical Activity and Cancer Outcomes: A Precision Medicine Approach. AB - There is increasing interest in applying a precision medicine approach to understanding exercise as a potential treatment for cancer. We aimed to inform this new approach by appraising epidemiologic literature relating postdiagnosis physical activity to cancer outcomes overall and by molecular/genetic subgroups. Across 26 studies of breast, colorectal, and prostate cancer patients, a 37% reduction was seen in risk of cancer-specific mortality, comparing the most versus the least active patients (pooled relative risk = 0.63; 95% confidence interval: 0.54-0.73). Risks of recurrence or recurrence/cancer-specific death (combined outcome) were also reduced based on fewer studies. We identified ten studies of associations between physical activity and cancer outcomes by molecular or genetic markers. Two studies showed statistically significant risk reductions in breast cancer mortality/recurrence for the most (versus least) physically active estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) patients, while others showed risk reductions among ER-PR- and triple negative patients. In colorectal cancer, four studies showed statistically significant risk reductions in cancer-specific mortality for patients with high (versus low) physical activity and P21 expression, P27 expression, nuclear CTNNB1 , PTGS2 (COX-2)+, or IRS1 low/negative status. One prostate cancer study showed effect modification by Gleason score. As a means to enhance this evidence, future observational studies are needed that will measure physical activity objectively before and after diagnosis, use standardized definitions for outcomes, control for competing risks, assess nonlinear dose-response relations, and consider reverse causality. Ultimately, randomized controlled trials with clinical cancer outcomes and a correlative component will provide the best evidence of causality, relating exercise to cancer outcomes, overall and for molecular and genetic subgroups. Clin Cancer Res; 22(19); 4766-75. (c)2016 AACR. PMID- 27407092 TI - Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell-like Phenotype via Dysregulation of PITX2. AB - PURPOSE: We previously reported the oncogenic role of paired-like homeodomain 2 (PITX2) in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify the miRNA regulators of PITX2 and the mechanism underlying the pathogenesis of ESCC. EXPERIMENTAL DESIGN: Using miRNA profiling and bioinformatics analyses, we identified miR-644a as a negative mediator of PITX2 in ESCC. A series of in vivo and in vitro assays were performed to confirm the effect of miR-644a on PITX2-mediated ESCC malignancy. RESULTS: ESCC cells and tissues expressed less miR-644a than normal epithelial controls. In patient samples, lower expression of miR-644a in ESCC tissues was significantly correlated with tumor recurrence and/or metastasis, such that miR-644a, PITX2, and the combination of the two were independent prognostic indicators for ESCC patient's survival (P < 0.05). Gain- and loss-of-function studies demonstrated that miR-644a inhibited ESCC cell growth, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo In addition, miR-644a dramatically suppressed self-renewal and stem cell-like traits in ESCC cells. Furthermore, the effect of upregulation of miR-644a was similar to that of PITX2 knockdown in ESCC cells. Mechanistic studies revealed that miR-644a attenuates ESCC cells' malignancy and stem cell-associated phenotype, at least partially, by inactivation of the Akt/GSK-3beta/beta-catenin signaling pathway through PITX2. Furthermore, promoter hypermethylation caused downregulation of miR-644a in ESCC. CONCLUSIONS: Downregulation of miR-644a plays an important role in promoting both aggressiveness and stem-like traits of ESCC cells, suggesting that miR-644a may be useful as a novel prognostic biomarker or therapeutic target for the disease. Clin Cancer Res; 23(1); 298-310. (c)2016 AACR. PMID- 27407095 TI - Intravaginal Administration of Fc-Fused IL7 Suppresses the Cervicovaginal Tumor by Recruiting HPV DNA Vaccine-Induced CD8 T Cells. AB - PURPOSE: The induction of tissue-localized virus-specific CD8 T-cell response is essential for the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. Here, we aimed to elucidate the immunologic role of IL7 in the induction of mucosal cellular immunity. EXPERIMENTAL DESIGN: IL7 was engineered through Fc fusion to enhance mucosal delivery across the genital epithelial barrier. The immunomodulatory role of IL7 was evaluated by monitoring the kinetics of various immune cells and measuring the expression of chemokines and cytokines after intravaginal administration of Fc-fused IL7 (IL7-Fc). The antitumor effects of intramuscular human papillomavirus (HPV) DNA vaccine or topical IL7-Fc alone or in a combinational regimen on mice survival were compared using a orthotopic cervical cancer model. RESULTS: Intravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFNgamma, TNFalpha, IL6, and IL1beta), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, gammadelta T cells, and dendritic cells. Importantly, in this murine cervical cancer model, topical administration of IL7-Fc after intramuscular HPV DNA vaccination increases the number of HPV-specific CD8 T cells in the genital mucosa, but not in the spleen, leading to stronger antitumor activity than the HPV DNA vaccine alone. CONCLUSIONS: Our findings provide an important insight into the immunomodulatory role of IL7-Fc via topical application and the design of therapeutic vaccine regimen that induces effective genital-mucosal CD8 T-cell responses. Clin Cancer Res; 22(23); 5898-908. (c)2016 AACR. PMID- 27407094 TI - Alternative Lengthening of Telomeres and Loss of DAXX/ATRX Expression Predicts Metastatic Disease and Poor Survival in Patients with Pancreatic Neuroendocrine Tumors. AB - PURPOSE: Pancreatic neuroendocrine tumors (PanNET) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing has identified recurrent mutations in the genes DAXX and ATRX, which correlate with loss of protein expression and alternative lengthening of telomeres (ALT). Both ALT and DAXX/ATRX loss were initially reported to be associated with a favorable prognosis; however, recent studies suggest the contrary. Our aims were to assess the prevalence and prognostic significance of ALT and DAXX/ATRX in both primary and metastatic PanNETs. EXPERIMENTAL DESIGN: Telomere-specific FISH and DAXX/ATRX IHC was performed on a multi-institutional cohort of 321 patients with resected PanNET and 191 distant metastases from 52 patients. These results were correlated with clinicopathologic features, including disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: The prevalence of ALT and DAXX/ATRX loss in resected PanNETs was 31% and 26%, respectively, and associated with larger tumor size, higher WHO grade, lymph node metastasis, and distant metastasis (P < 0.001). The 5-year DFS and 10-year DSS of patients with ALT-positive and DAXX/ATRX-negative PanNETs were 40% and 50%, respectively, as compared with 96% and 89%, respectively, for wild-type PanNETs. Among distant metastases, ALT and DAXX/ATRX loss was 67% and 52%, respectively, and only occurred in the setting of an ALT-positive and DAXX/ATRX negative primary PanNET. By multivariate analysis, both ALT and DAXX/ATRX loss were negative, independent prognostic factors for DFS. CONCLUSIONS: ALT and DAXX/ATRX loss in PanNETs was associated with shorter DFS and DSS and likely plays a significant role in driving metastatic disease. Clin Cancer Res; 23(2); 600-9. (c)2016 AACR. PMID- 27407096 TI - Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. AB - Despite more than two decades of publications that offer more innovative model based designs, the classical 3 + 3 design remains the most dominant phase I trial design in practice. In this article, we introduce a new trial design, the Bayesian optimal interval (BOIN) design. The BOIN design is easy to implement in a way similar to the 3 + 3 design, but is more flexible for choosing the target toxicity rate and cohort size and yields a substantially better performance that is comparable with that of more complex model-based designs. The BOIN design contains the 3 + 3 design and the accelerated titration design as special cases, thus linking it to established phase I approaches. A numerical study shows that the BOIN design generally outperforms the 3 + 3 design and the modified toxicity probability interval (mTPI) design. The BOIN design is more likely than the 3 + 3 design to correctly select the MTD and allocate more patients to the MTD. Compared with the mTPI design, the BOIN design has a substantially lower risk of overdosing patients and generally a higher probability of correctly selecting the MTD. User-friendly software is freely available to facilitate the application of the BOIN design. Clin Cancer Res; 22(17); 4291-301. (c)2016 AACR. PMID- 27407097 TI - TXR1 and TSP1 expression varies by the molecular subtypes of breast cancer patients who received previous docetaxel-based first-line chemotherapy. AB - The expression of taxol resistance gene 1 and thrombospondin 1 remains unknown in human breast cancer tissues. In the current study, we sought to measure the mRNA expression levels of taxol resistance gene 1 and thrombospondin 1 in breast cancer tissue and adjacent normal tissue specimens and further analyzed their expression according to the molecular subtypes and age of breast cancer patients who had received taxane-containing regimens. Archived breast cancer and adjacent non-tumor tissue specimens were obtained at Beijing Friendship Hospital, Beijing, China. The mRNA transcript levels of taxol resistance gene 1, thrombospondin 1 and multi-drug resistance 1 were determined by quantitative RT-PCR. Taxol resistance gene 1 and multi-drug resistance 1 protein levels were measured by immunoblotting assays. Forty-nine archived breast cancer tissue specimens were included. The majority of the specimens (65.3%) were of the molecular subtype A followed by triple negative breast cancer (14.3%). The mRNA transcript levels of taxol resistance gene 1 , thrombospondin 1 and multi-drug resistance 1 in breast cancer tissues were higher than those of adjacent normal tissues. The mRNA expression of TXR1 in the HER2 subtype (4.513 +/- 0.810) was the highest and in the Luminal B subtype was the lowest (3.103 +/- 0.417) among the four molecular subtypes. The HER2 subtype also had the highest mRNA expression of thrombospondin 1(4.827 +/- 0.927) and the Luminal B subtype had the lowest TSP1 mRNA level (3.197 +/- 0.565) among the four molecular subtypes. Our study represents the first attempt in delineating taxol resistance gene 1 and thrombospondin 1 expression in breast cancer and we demonstrate that taxol resistance gene 1 and thrombospondin 1 expression may vary according to the molecular subtypes of breast cancer. PMID- 27407098 TI - Intermittent hypoxia training as non-pharmacologic therapy for cardiovascular diseases: Practical analysis on methods and equipment. AB - The global industrialization has brought profound lifestyle changes and environmental pollutions leading to higher risks of cardiovascular diseases. Such tremendous challenges outweigh the benefits of major advances in pharmacotherapies (such as statins, antihypertensive, antithrombotic drugs) and exacerbate the public healthcare burdens. One of the promising complementary non pharmacologic therapies is the so-called intermittent hypoxia training (IHT) via activation of the human body's own natural defense through adaptation to intermittent hypoxia. This review article primarily focuses on the practical questions concerning the utilization of IHT as a non-pharmacologic therapy against cardiovascular diseases in humans. Evidence accumulated in the past five decades of research in healthy men and patients has suggested that short-term daily sessions consisting 3-4 bouts of 5-7 min exposures to 12-10% O2 alternating with normoxic durations for 2-3 weeks can result in remarkable beneficial effects in treatment of cardiovascular diseases such as hypertension, coronary heart disease, and heart failure. Special attentions are paid to the therapeutic effects of different IHT models, along with introduction of a variety of specialized facilities and equipment available for IHT, including hypobaric chambers, hypoxia gas mixture deliver equipment (rooms, tents, face masks), and portable rebreathing devices. Further clinical trials and thorough evaluations of the risks versus benefits of IHT are much needed to develop a series of standardized and practical guidelines for IHT. Taken together, we can envisage a bright future for IHT to play a more significant role in the preventive and complementary medicine against cardiovascular diseases. PMID- 27407099 TI - Cardiac rehabilitation improves the blood plasma properties of cardiac patients. AB - Cardiac rehabilitation (CR) improves exercise tolerance and general function. However, its effects on blood plasma in cardiac patients remain uncertain. Our aim was to examine the effect of comprehensive CR on the oxidative stress parameters and antioxidant plasma status in patients with coronary artery disease (CAD) after cardiac interventions. Exercise-based rehabilitation was established as ergometer training, adjusted for individual patients' physical efficiency. Training was repeated three times a week for two months. The standard biochemical (total cholesterol, HDL, LDL, triglycerides and erythrocyte sedimentation rate) and metabolic parameters (peak oxygen uptake [VO2] and peak workload) were determined. We assessed plasma viscosity, lipid peroxidation, carbonyl compounds levels, glutathione (GSH) and ascorbate (ASC) levels and the non-enzymatic antioxidant capacity of plasma in 12 patients with CAD before and after CR. Parameters were examined before exercise, immediately after exercise, and 1 h later. We also compared morphological and biochemical parameters of blood, as well as other parameters such as heart rate and blood pressure (resting and exercise), VO2max and peak workload (W) before and after CR. Before CR, a significant decrease in GSH concentration was observed 1 h after exercise. Conversely, after CR, GSH, and ASC levels remained unchanged immediately after exercise. However, ASC increased after CR after exercise and 1 h later in comparison to before CR. There was a significant increase in ferric reduction ability of plasma immediately after exercise after CR, when compared with before CR. CR improved several blood biochemical parameters, peak VO2, induced an increase in systolic blood pressure peak, and patients' peak workload. After CR, improvements were detected in oxidative stress parameters, except in the level of carbonyls. These changes may contribute to the increased functional heart capacity and better tolerance to exercise and functional capacity of the patients. These improvements could indicate better prognosis of future cardiac events and hospitalization and better quality of life. PMID- 27407100 TI - Poor concordance between CA-125 and RECIST at the time of disease progression in patients with platinum-resistant ovarian cancer: analysis of the AURELIA trial. AB - BACKGROUND: Data on CA-125 as a predictor of disease progression (PD) in ovarian cancer come predominantly from patients with platinum-sensitive disease receiving chemotherapy alone. We assessed concordance between CA-125-defined and RECIST defined PD using data from the Gynecologic Cancer InterGroup (GCIG) randomized phase III AURELIA trial in platinum-resistant ovarian cancer (PROC). PATIENTS AND METHODS: Patients with PROC were randomized to receive single-agent chemotherapy with or without bevacizumab. PD by CA-125 was defined according to GCIG criteria (except that confirmatory CA-125 measurement was not required). This exploratory analysis included patients with RECIST PD and a CA-125 reading <=28 days before and <=21 days after RECIST-defined PD. RESULTS: Of 218 eligible patients, only 94 (43%, 95% confidence interval 36% to 50%) had concordant RECIST and CA-125 PD status (42% in the chemotherapy-alone arm; 45% in the bevacizumab combination arm, P = 0.6). There was no evidence of CA-125-defined PD in the remaining 124 patients despite PD according to imaging. There were no significant differences in baseline characteristics between patients with PD defined by both RECIST and CA-125 and those with RECIST-only PD. CA-125 was even less sensitive in detecting PD in patients with early (<8 weeks after randomization) compared with later RECIST-defined PD (69% versus 53%, respectively, not meeting CA-125 criteria; P = 0.053). There was no significant difference in survival after PD in patients with concordant PD by RECIST and CA-125 versus those with PD only by RECIST. We validated our findings in an independent study population of PROC. CONCLUSIONS: In this platinum-resistant population, PD was typically detected earlier by imaging than by CA-125, irrespective of bevacizumab treatment. Disease status by CA-125 at the time of PD was not prognostic for overall survival. Regular radiologic assessment as well as symptom benefit assessment should be considered during PROC follow-up. PMID- 27407101 TI - When It's Bad to Be Friendly and Smart: The Desirability of Sociability and Competence Depends on Morality. AB - Morality, sociability, and competence are distinct dimensions in person perception. We argue that a person's morality informs us about their likely intentions, whereas their competence and sociability inform us about the likelihood that they will fulfill those intentions. Accordingly, we hypothesized that whereas morality would be considered unconditionally positive, sociability and competence would be highly positive only in moral others, and would be less positive in immoral others. Using exploratory factor analyses, Studies 1a and 1b distinguished evaluations of morality and sociability. Studies 2 to 5 then showed that sociability and competence are evaluated positively contingent on morality Study 2 demonstrated this phenomenon, while the remaining studies explained it (Study 3), generalized it (Studies 3-5), and ruled out an alternative explanation for it (Study 5). Study 6 showed that the positivity of morality traits is independent of other morality traits. These results support a functionalist account of these dimensions of person perception. PMID- 27407102 TI - An ancestral stomatal patterning module revealed in the non-vascular land plant Physcomitrella patens. AB - The patterning of stomata plays a vital role in plant development and has emerged as a paradigm for the role of peptide signals in the spatial control of cellular differentiation. Research in Arabidopsis has identified a series of epidermal patterning factors (EPFs), which interact with an array of membrane-localised receptors and associated proteins (encoded by ERECTA and TMM genes) to control stomatal density and distribution. However, although it is well-established that stomata arose very early in the evolution of land plants, until now it has been unclear whether the established angiosperm stomatal patterning system represented by the EPF/TMM/ERECTA module reflects a conserved, universal mechanism in the plant kingdom. Here, we use molecular genetics to show that the moss Physcomitrella patens has conserved homologues of angiosperm EPF, TMM and at least one ERECTA gene that function together to permit the correct patterning of stomata and that, moreover, elements of the module retain function when transferred to Arabidopsis Our data characterise the stomatal patterning system in an evolutionarily distinct branch of plants and support the hypothesis that the EPF/TMM/ERECTA module represents an ancient patterning system. PMID- 27407103 TI - Novel functions for Dorsocross in epithelial morphogenesis in the beetle Tribolium castaneum. AB - Epithelial morphogenesis, the progressive restructuring of tissue sheets, is fundamental to embryogenesis. In insects, not only embryonic tissues but also extraembryonic (EE) epithelia play a crucial role in shaping the embryo. In Drosophila, the T-box transcription factor Dorsocross (Doc) is essential for EE tissue maintenance and therefore embryo survival. However, Drosophila possesses a single amnioserosa, whereas most insects have a distinct amnion and serosa. How does this derived situation compare with Doc function in the ancestral context of two EE epithelia? Here, we investigate the Doc orthologue in the red flour beetle, Tribolium castaneum, which is an excellent model for EE tissue complement and for functional, fluorescent live imaging approaches. Surprisingly, we find that Tc-Doc controls all major events in Tribolium EE morphogenesis without affecting EE tissue specification or maintenance. These macroevolutionary changes in function between Tribolium and Drosophila are accompanied by regulatory network changes, where BMP signaling and possibly the transcription factor Hindsight are downstream mediators. We propose that the ancestral role of Doc was to control morphogenesis and discuss how Tc-Doc could provide spatial precision for remodeling the amnion-serosa border. PMID- 27407105 TI - DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach. AB - In eukaryotic cells the CDC7/DBF4 kinase, also known as DBF4-dependent kinase (DDK), is required for the firing of DNA replication origins. CDC7 is also involved in replication stress responses and its depletion sensitises cells to drugs that affect fork progression, including Topoisomerase 2 poisons. Although CDC7 is an important regulator of cell division, relatively few substrates and bona-fide CDC7 phosphorylation sites have been identified to date in human cells. In this study, we have generated an active recombinant CDC7/DBF4 kinase that can utilize bulky ATP analogues. By performing in vitro kinase assays using benzyl thio-ATP, we have identified TOP2A as a primary CDC7 substrate in nuclear extracts, and serine 1213 and serine 1525 as in vitro phosphorylation sites. We show that CDC7/DBF4 and TOP2A interact in cells, that this interaction mainly occurs early in S-phase, and that it is compromised after treatment with CDC7 inhibitors. We further provide evidence that human DBF4 localises at centromeres, to which TOP2A is progressively recruited during S-phase. Importantly, we found that CDC7/DBF4 down-regulation, as well S1213A/S1525A TOP2A mutations can advance the timing of centromeric TOP2A recruitment in S-phase. Our results indicate that TOP2A is a novel DDK target and have important implications for centromere biology. PMID- 27407104 TI - The target spectrum of SdsR small RNA in Salmonella. AB - Model enteric bacteria such as Escherichia coli and Salmonella enterica express hundreds of small non-coding RNAs (sRNAs), targets for most of which are yet unknown. Some sRNAs are remarkably well conserved, indicating that they serve cellular functions that go beyond the necessities of a single species. One of these 'core sRNAs' of largely unknown function is the abundant ~100-nucleotide SdsR sRNA which is transcribed by the general stress sigma-factor, sigmaS and accumulates in stationary phase. In Salmonella, SdsR was known to inhibit the synthesis of the species-specific porin, OmpD. However, sdsR genes are present in almost all enterobacterial genomes, suggesting that additional, conserved targets of this sRNA must exist. Here, we have combined SdsR pulse-expression with whole genome transcriptomics to discover 20 previously unknown candidate targets of SdsR which include mRNAs coding for physiologically important regulators such as the carbon utilization regulator, CRP, the nucleoid-associated chaperone, StpA and the antibiotic resistance transporter, TolC. Processing of SdsR by RNase E results in two cellular SdsR variants with distinct target spectra. While the overall physiological role of this orphan core sRNA remains to be fully understood, the new SdsR targets present valuable leads to determine sRNA functions in resting bacteria. PMID- 27407106 TI - Free energy analysis and mechanism of base pair stacking in nicked DNA. AB - The equilibrium of stacked and unstacked base pairs is of central importance for all nucleic acid structure formation processes. The stacking equilibrium is influenced by intramolecular interactions between nucleosides but also by interactions with the solvent. Realistic simulations on nucleic acid structure formation and flexibility require an accurate description of the stacking geometry and stability and its sequence dependence. Free energy simulations have been conducted on a series of double stranded DNA molecules with a central strand break (nick) in one strand. The change in free energy upon unstacking was calculated for all ten possible base pair steps using umbrella sampling along a center-of-mass separation coordinate and including a comparison of different water models. Comparison to experimental studies indicates qualitative agreement of the stability order but a general overestimation of base pair stacking interactions in the simulations. A significant dependence of calculated nucleobase stacking free energies on the employed water model was observed with the tendency of stacking free energies being more accurately reproduced by more complex water models. The simulation studies also suggest a mechanism of stacking/unstacking that involves significant motions perpendicular to the reaction coordinate and indicate that the equilibrium nicked base pair step may slightly differ from regular B-DNA geometry in a sequence-dependent manner. PMID- 27407107 TI - Investigating essential gene function in Mycobacterium tuberculosis using an efficient CRISPR interference system. AB - Despite many methodological advances that have facilitated investigation of Mycobacterium tuberculosis pathogenesis, analysis of essential gene function in this slow-growing pathogen remains difficult. Here, we describe an optimized CRISPR-based method to inhibit expression of essential genes based on the inducible expression of an enzymatically inactive Cas9 protein together with gene specific guide RNAs (CRISPR interference). Using this system to target several essential genes of M. tuberculosis, we achieved marked inhibition of gene expression resulting in growth inhibition, changes in susceptibility to small molecule inhibitors and disruption of normal cell morphology. Analysis of expression of genes containing sequences similar to those targeted by individual guide RNAs did not reveal significant off-target effects. Advantages of this approach include the ability to compare inhibited gene expression to native levels of expression, lack of the need to alter the M. tuberculosis chromosome, the potential to titrate the extent of transcription inhibition, and the ability to avoid off-target effects. Based on the consistent inhibition of transcription and the simple cloning strategy described in this work, CRISPR interference provides an efficient approach to investigate essential gene function that may be particularly useful in characterizing genes of unknown function and potential targets for novel small molecule inhibitors. PMID- 27407108 TI - Identification of the mRNA targets of tRNA-specific regulation using genome-wide simulation of translation. AB - tRNA gene copy number is a primary determinant of tRNA abundance and therefore the rate at which each tRNA delivers amino acids to the ribosome during translation. Low-abundance tRNAs decode rare codons slowly, but it is unclear which genes might be subject to tRNA-mediated regulation of expression. Here, those mRNA targets were identified via global simulation of translation. In silico mRNA translation rates were compared for each mRNA in both wild-type and a [Formula: see text] sup70-65 mutant, which exhibits a pseudohyphal growth phenotype and a 75% slower CAG codon translation rate. Of 4900 CAG-containing mRNAs, 300 showed significantly reduced in silico translation rates in a simulated tRNA mutant. Quantitative immunoassay confirmed that the reduced translation rates of sensitive mRNAs were [Formula: see text] concentration dependent. Translation simulations showed that reduced [Formula: see text] concentrations triggered ribosome queues, which dissipated at reduced translation initiation rates. To validate this prediction experimentally, constitutive gcn2 kinase mutants were used to reduce in vivo translation initiation rates. This repaired the relative translational rate defect of target mRNAs in the sup70-65 background, and ameliorated sup70-65 pseudohyphal growth phenotypes. We thus validate global simulation of translation as a new tool to identify mRNA targets of tRNA-specific gene regulation. PMID- 27407109 TI - Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases. AB - Genome wide association studies (GWAS) provide a powerful approach for uncovering disease-associated variants in human, but fine-mapping the causal variants remains a challenge. This is partly remedied by prioritization of disease associated variants that overlap GWAS-enriched epigenomic annotations. Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations. In simulation, RiVIERA promising power in detecting causal variants and causal annotations, the multi-trait joint inference further improved the detection power. We applied RiVIERA to model the existing GWAS summary statistics of 9 autoimmune diseases and Schizophrenia by jointly harnessing the potential causal enrichments among 848 tissue-specific epigenomics annotations from ENCODE/Roadmap consortium covering 127 cell/tissue types and 8 major epigenomic marks. RiVIERA identified meaningful tissue-specific enrichments for enhancer regions defined by H3K4me1 and H3K27ac for Blood T-Cell specifically in the nine autoimmune diseases and Brain-specific enhancer activities exclusively in Schizophrenia. Moreover, the variants from the 95% credible sets exhibited high conservation and enrichments for GTEx whole-blood eQTLs located within transcription-factor-binding-sites and DNA-hypersensitive-sites. Furthermore, joint modeling the nine immune traits by simultaneously inferring and exploiting the underlying epigenomic correlation between traits further improved the functional enrichments compared to single trait models. PMID- 27407110 TI - Global transcript structure resolution of high gene density genomes through multi platform data integration. AB - Annotation of herpesvirus genomes has traditionally been undertaken through the detection of open reading frames and other genomic motifs, supplemented with sequencing of individual cDNAs. Second generation sequencing and high-density microarray studies have revealed vastly greater herpesvirus transcriptome complexity than is captured by existing annotation. The pervasive nature of overlapping transcription throughout herpesvirus genomes, however, poses substantial problems in resolving transcript structures using these methods alone. We present an approach that combines the unique attributes of Pacific Biosciences Iso-Seq long-read, Illumina short-read and deepCAGE (Cap Analysis of Gene Expression) sequencing to globally resolve polyadenylated isoform structures in replicating Epstein-Barr virus (EBV). Our method, Transcriptome Resolution through Integration of Multi-platform Data (TRIMD), identifies nearly 300 novel EBV transcripts, quadrupling the size of the annotated viral transcriptome. These findings illustrate an array of mechanisms through which EBV achieves functional diversity in its relatively small, compact genome including programmed alternative splicing (e.g. across the IR1 repeats), alternative promoter usage by LMP2 and other latency-associated transcripts, intergenic splicing at the BZLF2 locus, and antisense transcription and pervasive readthrough transcription throughout the genome. PMID- 27407111 TI - Different N-terminal isoforms of Oct-1 control expression of distinct sets of genes and their high levels in Namalwa Burkitt's lymphoma cells affect a wide range of cellular processes. AB - Oct-1 transcription factor has various functions in gene regulation. Its expression level is increased in several types of cancer and is associated with poor survival prognosis. Here we identified distinct Oct-1 protein isoforms in human cells and compared gene expression patterns and functions for Oct-1A, Oct 1L, and Oct-1X isoforms that differ by their N-terminal sequences. The longest isoform, Oct-1A, is abundantly expressed and is the main Oct-1 isoform in most of human tissues. The Oct-1L and the weakly expressed Oct-1X regulate the majority of Oct-1A targets as well as additional sets of genes. Oct-1X controls genes involved in DNA replication, DNA repair, RNA processing, and cellular response to stress. The high level of Oct-1 isoforms upregulates genes related to cell cycle progression and activates proliferation both in Namalwa Burkitt's lymphoma cells and primary human fibroblasts. It downregulates expression of genes related to antigen processing and presentation, cytokine-cytokine receptor interaction, oxidative metabolism, and cell adhesion, thus facilitating pro-oncogenic processes. PMID- 27407113 TI - S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells. AB - MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery. PMID- 27407114 TI - Multiple consecutive initiation of replication producing novel brush-like intermediates at the termini of linear viral dsDNA genomes with hairpin ends. AB - Linear dsDNA replicons with hairpin ends are found in the three domains of life, mainly associated with plasmids and viruses including the poxviruses, some phages and archaeal rudiviruses. However, their replication mechanism is not clearly understood. In this study, we find that the rudivirus SIRV2 undergoes multiple consecutive replication reinitiation events at the genomic termini. Using a strand-displacement replication strategy, the multiple reinitiation events from one parental template yield highly branched intermediates corresponding to about 30 genome units which generate exceptional 'brush-like' structures. Moreover, our data support the occurrence of an additional strand-coupled bidirectional replication from a circular dimeric intermediate. The multiple reinitiation process ensures rapid copying of the parental viral genome and will enable protein factors involved in viral genome replication to be specifically localised intracellularly, thereby helping the virus to avoid host defence mechanisms. PMID- 27407115 TI - Presidential Address: The New Image of Health-System Pharmacists in New York State. PMID- 27407112 TI - Novel small molecules potentiate premature termination codon readthrough by aminoglycosides. AB - Nonsense mutations introduce premature termination codons and underlie 11% of genetic disease cases. High concentrations of aminoglycosides can restore gene function by eliciting premature termination codon readthrough but with low efficiency. Using a high-throughput screen, we identified compounds that potentiate readthrough by aminoglycosides at multiple nonsense alleles in yeast. Chemical optimization generated phthalimide derivative CDX5-1 with activity in human cells. Alone, CDX5-1 did not induce readthrough or increase TP53 mRNA levels in HDQ-P1 cancer cells with a homozygous TP53 nonsense mutation. However, in combination with aminoglycoside G418, it enhanced readthrough up to 180-fold over G418 alone. The combination also increased readthrough at all three nonsense codons in cancer cells with other TP53 nonsense mutations, as well as in cells from rare genetic disease patients with nonsense mutations in the CLN2, SMARCAL1 and DMD genes. These findings open up the possibility of treating patients across a spectrum of genetic diseases caused by nonsense mutations. PMID- 27407116 TI - NYSCHP Residency Research & Practice Forum 2016: Platform Presentation Abstracts. PMID- 27407118 TI - Of Kith and Kin: Perceptual Enrichment, Expectancy, and Reciprocity in Face Perception. AB - Race powerfully affects perceivers' responses to faces, promoting biases in attention, classification, and memory. To account for these diverse effects, we propose a model that integrates social cognitive work with two prominent accounts of visual processing: perceptual learning and predictive coding. Our argument is that differential experience with a racial ingroup promotes both (a) perceptual enrichment, including richer, more well-integrated visual representations of ingroup relative to outgroup faces, and (b) expectancies that ingroup faces are normative, which influence subsequent visual processing. By allowing for "top down" expectancy-based processes, this model accounts for both experience- and non-experience-based influences, such as motivation, context, and task instructions. Fundamentally, we suggest that we treat race as an important psychological dimension because it structures our social environment, which in turn structures mental representation. PMID- 27407117 TI - Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of beta-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. AB - OBJECTIVE: Standardized, reproducible, and feasible quantification of beta-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS: Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (~50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ~0.3 to ~0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS: Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. PMID- 27407120 TI - The Greatest Show on Earth! PMID- 27407121 TI - Advances in the Care of Adult Patients With Acute Lymphoblastic Leukemia: Optimism Tempered by Reality. PMID- 27407119 TI - Chronic p38 mitogen-activated protein kinase inhibition improves vascular function and remodeling in angiotensin II-dependent hypertension. AB - INTRODUCTION: An excess of angiotensin II (Ang II) causes hypertension and vascular injury. Activation of mitogen-activated protein kinase p38 (p38-MAPK) plays a substantial role in Ang II-dependent organ damage. Recently, we showed that p38-MAPK activation regulates the pressor response to Ang II. This study evaluates the effect of chronic p38-MAPK inhibition in Ang II-dependent hypertension. MATERIALS AND METHODS: C57Bl/6J mice were infused with Ang II for 14 days and either treated with the p38-MAPK inhibitor BIRB796 (50 mg/kg/day) or the vehicle as the control. We assessed vascular function in the aorta and isolated perfused kidneys. RESULTS: Chronic p38-MAPK inhibition did not alter blood pressure at the baseline, but attenuated Ang II-induced hypertension significantly (baseline: 122 +/- 2 versus 119 +/- 4 mmHg; Ang II: 173 +/- 3 versus 155 +/- 3 mmHg; p < 0.001). In addition, BIRB796 treatment improved vascular remodeling by reducing the aortic media-to-lumen ratio and decreasing the expression of the membrane metalloproteinases (MMP) MMP-1 and MMP-9. Moreover, renal vascular dysfunction induced by chronic Ang II infusion was significantly ameliorated in the BIRP796-treated mice. Acute p38-MAPK inhibition also improved vascular function in the aorta and kidneys of Ang II-treated mice, highlighting the important role of p38-MAPK activation in the pathogenesis of vascular dysfunction. CONCLUSIONS: Our findings indicated there is an important role for p38-MAPK in regulating blood pressure and vascular injury, and highlighted its potential as a pharmaceutical target. PMID- 27407122 TI - Whole-Exome Sequencing in Two Extreme Phenotypes of Response to VEGF-Targeted Therapies in Patients With Metastatic Clear Cell Renal Cell Carcinoma. AB - Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC). Patients with mRCC who had received first-line sunitinib or pazopanib and were in 2 extreme phenotypes of response were identified. Extreme responders (ERs) were defined as those with partial response or complete response for 3 or more years (n=13) and primary refractory patients (PRPs) were defined as those with progressive disease within the first 3 months of therapy (n=14). International Metastatic RCC Database Consortium prognostic scores were not significantly different between the groups (P=.67). Considering the genes known to be mutated in RCC at significant frequency, PBRM1 mutations were identified in 7 ERs (54%) versus 1 PRP (7%) (P=.01). In addition, mutations in TP53 (n=4) were found only in PRPs (P=.09). Our data suggest that mutations in some genes in RCC may impact response to VEGF-TT. PMID- 27407123 TI - NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016. AB - These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making. PMID- 27407124 TI - Value, Access, and Cost of Cancer Care Delivery at Academic Cancer Centers. AB - Key challenges facing the oncology community today include access to appropriate, high quality, patient-centered cancer care; defining and delivering high-value care; and rising costs. The National Comprehensive Cancer Network convened a Work Group composed of NCCN Member Institution cancer center directors and their delegates to examine the challenges of access, high costs, and defining and demonstrating value at the academic cancer centers. The group identified key challenges and possible solutions to addressing these issues. The findings and recommendations of the Work Group were then presented at the Value, Access, and Cost of Cancer Care Policy Summit in September 2015 and multi-stakeholder roundtable panel discussions explored these findings and recommendations along with additional items. PMID- 27407125 TI - Adherence to Hematologic Hold Parameters in Carboplatin and Dose-Dense Paclitaxel Chemotherapy for Ovarian Malignancies: A Survey of NCCN Member Institutions. AB - OBJECTIVE: To determine the adherence to hematologic chemotherapy hold parameters for the carboplatin and dose-dense paclitaxel chemotherapy regimen in patients with ovarian, fallopian tube, or primary peritoneal cancers. METHODS: This is a quality assessment survey study. All 26 NCCN Member Institutions were contacted electronically. Hematologic chemotherapy hold parameter values (absolute neutrophil count [ANC] and platelet count) on days 1, 8, and 15 of each cycle were queried. These hold parameters were compared with published data supporting the use of dose-dense chemotherapy regimens in ovarian cancer. RESULTS: The overall survey response rate was 85% (22/26 sites). Of responders, 27% (6 sites) were fully adherent with all hematologic hold parameters and 64% (14 sites) used hold parameters that differed from the published protocol. Specifically, all of these sites use hold parameters higher than those recommended in the literature. Two centers did not have center-specific hold parameters. CONCLUSIONS: Carboplatin and dose-dense paclitaxel chemotherapy has been shown to increase progression-free survival and overall survival in patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancers. However, our study found that two-thirds of queried sites had hold parameters higher than those in the published protocol. Using more stringent hold parameters may lead to compromised clinical outcomes. Further research is necessary to determine the optimal strategy to increase individual site adherence to chemotherapy hematologic hold parameters as specified in published trials. PMID- 27407126 TI - The Current State of Palliative Care for Patients Cared for at Leading US Cancer Centers: The 2015 NCCN Palliative Care Survey. AB - BACKGROUND: ASCO and IOM recommend palliative care (PC) across health care settings for patients with serious illnesses, including cancer. This study provides an overview of the current availability, structure, and basic quality of PC services within NCCN Member Institutions. METHODS: A PC survey was developed by NCCN staff and a working group of PC experts from 11 NCCN Member Institutions under the auspices of the NCCN Best Practices Committee. The survey was piloted and refined by 3 working group members and sent electronically to all 26 NCCN Member Institutions. NCCN staff and working group leaders analyzed the survey data. RESULTS: A total of 22 of 26 institutions responded (85%). All respondents (100%) reported an inpatient PC consult service (staffed by an average of 6.8 full-time equivalents [FTEs], seeing 1,031 consults/year with an average length of stay [LOS] of 10 days). A total of 91% of respondents had clinic-based PC (with an average of 469 consults/year, staffed by an average of 6.8 FTEs, and a 17-day wait time). For clinics, a comanagement care delivery model was more common than strict consultation. Home-based PC (23%) and inpatient PC units (32%) were less prevalent. Notably, 80% of institutions reported insufficient PC capacity compared with demand. Across PC settings, referrals for patients with solid tumors were more common than for hematologic malignancies. Automatic or "triggered" referrals were rare. The most common services provided were symptom management (100%) and advance care planning (96%). Most programs were funded through fee-for-service billing and institutional support. Partnerships with accountable care organizations and bundled payment arrangements were infrequent. PC program data collection and institutional funding for PC research were variable across institutions. CONCLUSIONS: Despite the prevalence of PC inpatient and clinic services among participating NCCN Member Institutions, PC demand still exceeds capacity. Opportunities exist for expansion of home-based PC and inpatient PC units, optimizing referrals, research, and payer collaborations. PMID- 27407127 TI - Care and Outcomes of Patients With Cancer Admitted to the Hospital on Weekends and Holidays: A Retrospective Cohort Study. AB - BACKGROUND: Patients admitted to the hospital on weekends experience worse outcomes than those admitted on weekdays. Patients with cancer may be especially vulnerable to the effects of weekend care. Our objective was to compare the care and outcomes of patients with cancer admitted urgently to the hospital on weekends and holidays versus those of patients with cancer admitted at other times. MATERIALS AND METHODS: This was a retrospective study of all adult patients with cancer having an urgent hospitalization in Canada from 2010 to 2013. Patients admitted to hospital on weekends/holidays were compared with those admitted on weekdays. The primary outcome was 7-day in-hospital mortality. We also compared performance of procedures in the first 2 days of hospital admission and admission to critical care after the first 24 hours. RESULTS: 290,471 hospital admissions were included. Patients admitted to hospital on weekends/holidays had an increased risk of 7-day in-hospital mortality (4.8% vs 4.3%; adjusted odds ratio [OR], 1.13; 95% CI, 1.08-1.17), corresponding to 137 excess deaths per year compared with the weekday group. This risk persisted after restricting the analysis to patients arriving by ambulance (7.1% vs 6.4%; adjusted OR, 1.11; 95% CI, 1.04-1.18). Among those who had procedures in the first 4 days of admission, fewer weekend/holiday-admitted patients had them performed in the first 2 days, for 8 of 9 common procedure groups. There was no difference in critical care admission risk after the first 24 hours. CONCLUSIONS: Patients with cancer admitted to the hospital on weekends/holidays experience higher mortality relative to patients admitted on weekdays. This may result from different care processes for weekend/holiday patients, including delayed procedures. Future research is needed to identify key outcome-driving procedures, and ensure timely access to these on all days of the week. PMID- 27407128 TI - Bone Mineral Density Testing Disparities Among Patients With Breast Cancer Prescribed Aromatase Inhibitors. AB - OBJECTIVES: Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with early-stage, estrogen receptor-positive breast cancer. We designed our study to determine whether women initiating adjuvant therapy with an AI underwent baseline bone mineral density testing, as well as what factors predicted adherence with testing guidelines. METHODS: Medicare Parts A, B, and D claims were used to identify a cohort of women aged 67 years and older with incident breast cancer in 2006 and 2007 who started AI therapy. Medicare claims provided information about bone density testing, as well as demographic and other treatment data through 2012. We also ascertained which patients were treated with bisphosphonates and studied the relationship of bisphosphonate therapy with bone density testing. RESULTS: Approximately two-thirds of patients had baseline bone density testing. Older age, comorbidity, low income, and black race were associated with lower rates of baseline bone density testing. Testing rates decreased substantially with increasing age from 73% for women aged 67 to 70 years to 51% for those 85 years of age and older (adjusted odds ratio for not being tested, 2.48 [Cl, 2.17-2.82]). The proportion of women who had neither bone density testing nor bisphosphonate therapy increased with age as well. CONCLUSIONS: Despite the importance of age as a risk factor for fractures, older women starting treatment with AIs for treatment of breast cancer are less likely to undergo recommended bone density assessment. PMID- 27407130 TI - Cannabinoids for Symptom Management and Cancer Therapy: The Evidence. AB - Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids. Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain. Dronabinol and nabilone are better antiemetics for chemotherapy induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia. Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor. Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity. Paradoxically, cannabinoid receptor antagonists also have antitumor activity. There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using "medical marijuana" in this regard. PMID- 27407129 TI - Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. AB - Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed. PMID- 27407131 TI - Predictive Biomarkers for Molecularly Targeted Therapies in Renal Cell Carcinoma. PMID- 27407133 TI - Reconsidering Temporal Selection in the Attentional Blink. AB - Two episodes of attentional selection cannot occur very close in time. This is the traditional account of the attentional blink, whereby observers fail to report the second of two temporally proximal targets. Recent analyses have challenged this simple account, suggesting that attentional selection during the attentional blink is not only (a) suppressed, but also (b) temporally advanced then delayed, and (c) temporally diffused. Here, we reanalyzed six data sets using mixture modeling of report errors, and revealed much simpler dynamics. Exposing a problem inherent in previous analyses, we found evidence of a second attentional episode only when the second target (T2) follows the first (T1) by more than 100 to 250 ms. When a second episode occurs, suppression and delay reduce steadily as lag increases and temporal precision is stable. At shorter lags, both targets are reported from a single episode, which explains why T2 can escape the attentional blink when it immediately follows T1 (Lag-1 sparing). PMID- 27407134 TI - Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery. AB - Drug delivery in the CNS is limited by endothelial tight junctions forming the impermeable blood-brain barrier. The development of new treatment paradigms has previously been hampered by the restrictiveness of the blood-brain barrier to systemically administered therapeutics. With recent advances in stereotactic localization and noninvasive imaging, we have honed the ability to modulate, ablate, and rewire millimetric brain structures to precisely permeate the impregnable barrier. The wide range of focused radiations offers endless possibilities to disrupt endothelial permeability with different patterns and intensity following 3-dimensional coordinates offering a new world of possibilities to access the CNS, as well as to target therapies. We propose a review of the current state of knowledge in targeted drug delivery using noninvasive image-guided approaches. To this end, we focus on strategies currently used in clinics or in clinical trials such as targeted radiotherapy and magnetic resonance guided focused ultrasound, but also on more experimental approaches such as magnetically heated nanoparticles, electric fields, and lasers, techniques which demonstrated remarkable results both in vitro and in vivo. We envision that biodistribution and efficacy of systemically administered drugs will be enhanced with further developments of these promising strategies. Besides therapeutic applications, stereotactic platforms can be highly valuable in clinical applications for interventional strategies that can improve the targetability and efficacy of drugs and macromolecules. It is our hope that by showcasing and reviewing the current state of this field, we can lay the groundwork to guide future research in this realm. PMID- 27407135 TI - Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti dsDNA antibodies in systemic lupus erythematosus. AB - Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs. PMID- 27407136 TI - Effects of Exercise Intervention on Preventing Letrozole-Exposed Rats From Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development. PMID- 27407137 TI - Endometrial Expression of Homeobox Genes and Cell Adhesion Molecules in Infertile Women With Intramural Fibroids During Window of Implantation. AB - This study was designed to examine the expression and cellular distribution of homeobox ( HOX) genes ( HOXA10 and HOXA11) and cell adhesion molecules (E cadherin, N-cadherin, and beta-catenin) during the window of implantation in infertile women with noncavity-distorting intramural (IM) fibroids (n = 18) and in fertile controls (n = 12). Quantitative real-time polymerase chain reaction and immunohistochemistry were used to evaluate the messenger RNA (mRNA) levels and protein expression, respectively. When compared to fertile controls, reduced HOXA10 and HOXA11 transcript and protein levels were observed in infertile women. However, changes only in the expression of HOXA10 mRNA (-1.72-fold; P = .03) and stromal protein ( P = .001) were statistically significant. Significantly lower E cadherin mRNA (-10.97-fold; P = .02) and protein levels were seen in infertile patients. E-cadherin immunostaining was significantly reduced both in the luminal ( P = .048) and in the glandular ( P = .014) epithelium of endometrium from infertile patients when compared to controls. No significant change was observed either in the mRNA levels or in the immunoexpression of N-cadherin and beta catenin. However, a trend toward lower N-cadherin expression in the luminal epithelium ( P = .054) and decreased beta-catenin expression in the glandular epithelium ( P = .070) was observed in infertile patients. The present findings suggest that altered endometrial HOXA10 and E-cadherin mRNA and protein expression observed in infertile women with IM fibroids during the mid-secretory phase might impair endometrial receptivity leading to infertility in these patients. PMID- 27407138 TI - Elephant Trunk: Argument for All Arches. AB - Background Since Borst and colleagues first applied the elephant trunk technique more than 30 years ago, it has become a standard method in approach for staged repair of an extensive thoracic aneurysm. While the original technique was cumbersome, a number of innovations have significantly improved the results over the past 3 decades. Conclusions Today, total arch replacement with elephant trunk provides simplified staged surgery but, nonetheless, remains a complex surgical procedure. Although many proximal aortic procedures may be addressed with ascending and partial transverse arch replacement, when total or complete transverse arch replacement is required, then the use of the elephant trunk technique, whether standard or frozen, should be considered. PMID- 27407139 TI - A systems-oriented analysis of the grapevine R2R3-MYB transcription factor family uncovers new insights into the regulation of stilbene accumulation. AB - R2R3-MYB transcription factors (TFs) belong to a large and functionally diverse protein superfamily in plants. In this study, we explore the evolution and function of this family in grapevine (Vitis vinifera L.), a high-value fruit crop. We identified and manually curated 134 genes using RNA-Seq data, and named them systematically according to the Super-Nomenclature Committee. We identified novel genes, splicing variants and grapevine/woody-specific duplicated subgroups, suggesting possible neo- and sub-functionalization events. Regulatory network analysis ascribed biological functions to uncharacterized genes and validated those of known genes (e.g. secondary cell wall biogenesis and flavonoid biosynthesis). A comprehensive analysis of different MYB binding motifs in the promoters of co-expressed genes predicted grape R2R3-MYB binding preferences and supported evidence for putative downstream targets. Enrichment of cis-regulatory motifs for diverse TFs reinforced the notion of transcriptional coordination and interaction between MYBs and other regulators. Analysis of the network of Subgroup 2 showed that the resveratrol-related VviMYB14 and VviMYB15 share common co-expressed STILBENE SYNTHASE genes with the uncharacterized VviMYB13 These regulators have distinct expression patterns within organs and in response to biotic and abiotic stresses, suggesting a pivotal role of VviMYB13 in regulating stilbene accumulation in vegetative tissues and under biotic stress conditions. PMID- 27407141 TI - News Feature: Crucial role of belowground biodiversity. PMID- 27407144 TI - Globin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells. AB - The discovery of novel globins in diverse organisms has stimulated intense interest in their evolved function, beyond oxygen binding. Globin X (GbX) is a protein found in fish, amphibians, and reptiles that diverged from a common ancestor of mammalian hemoglobins and myoglobins. Like mammalian neuroglobin, GbX was first designated as a neuronal globin in fish and exhibits six-coordinate heme geometry, suggesting a role in intracellular electron transfer reactions rather than oxygen binding. Here, we report that GbX to our knowledge is the first six-coordinate globin and the first globin protein apart from hemoglobin, found in vertebrate RBCs. GbX is present in fish erythrocytes and exhibits a nitrite reduction rate up to 200-fold faster than human hemoglobin and up to 50 fold higher than neuroglobin or cytoglobin. Deoxygenated GbX reduces nitrite to form nitric oxide (NO) and potently inhibits platelet activation in vitro, to a greater extent than hemoglobin. Fish RBCs also reduce nitrite to NO and inhibit platelet activation to a greater extent than human RBCs, whereas GbX knockdown inhibits this nitrite-dependent NO signaling. The description of a novel, six coordinate globin in RBCs with dominant electron transfer and nitrite reduction functionality provides new insights into the evolved signaling properties of ancestral heme-globins. PMID- 27407143 TI - Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons. AB - The LIM-homeodomain transcription factors Lmx1a and Lmx1b play critical roles during the development of midbrain dopaminergic progenitors, but their functions in the adult brain remain poorly understood. We show here that sustained expression of Lmx1a and Lmx1b is required for the survival of adult midbrain dopaminergic neurons. Strikingly, inactivation of Lmx1a and Lmx1b recreates cellular features observed in Parkinson's disease. We found that Lmx1a/b control the expression of key genes involved in mitochondrial functions, and their ablation results in impaired respiratory chain activity, increased oxidative stress, and mitochondrial DNA damage. Lmx1a/b deficiency caused axonal pathology characterized by alpha-synuclein(+) inclusions, followed by a progressive loss of dopaminergic neurons. These results reveal the key role of these transcription factors beyond the early developmental stages and provide mechanistic links between mitochondrial dysfunctions, alpha-synuclein aggregation, and the survival of dopaminergic neurons. PMID- 27407145 TI - Minimal basilar membrane motion in low-frequency hearing. AB - Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that greatly increases the sound-evoked vibrations of the basilar membrane. We used laser interferometry in vitro and optical coherence tomography in vivo to study the low-frequency part of the guinea pig cochlea, and found that sound stimulation caused motion of a minimal portion of the basilar membrane. Outside the region of peak movement, an exponential decline in motion amplitude occurred across the basilar membrane. The moving region had different dependence on stimulus frequency than the vibrations measured near the mechanosensitive stereocilia. This behavior differs substantially from the behavior found in the extensively studied high-frequency regions of the cochlea. PMID- 27407146 TI - Single-molecule imaging reveals a common mechanism shared by G-quadruplex resolving helicases. AB - G-quadruplex (GQ) is a four stranded DNA secondary structure that arises from a guanine rich sequence. Stable formation of GQ in genomic DNA can be counteracted by the resolving activity of specialized helicases including RNA helicase AU (associated with AU rich elements) (RHAU) (G4 resolvase 1), Bloom helicase (BLM), and Werner helicase (WRN). However, their substrate specificity and the mechanism involved in GQ unfolding remain uncertain. Here, we report that RHAU, BLM, and WRN exhibit distinct GQ conformation specificity, but use a common mechanism of repetitive unfolding that leads to disrupting GQ structure multiple times in succession. Such unfolding activity of RHAU leads to efficient annealing exclusively within the same DNA molecule. The same resolving activity is sufficient to dislodge a stably bound GQ ligand, including BRACO-19, NMM, and Phen-DC3. Our study demonstrates a plausible biological scheme where different helicases are delegated to resolve specific GQ structures by using a common repetitive unfolding mechanism that provides a robust resolving power. PMID- 27407147 TI - The novel regulatory ncRNA, NfiS, optimizes nitrogen fixation via base pairing with the nitrogenase gene nifK mRNA in Pseudomonas stutzeri A1501. AB - Unlike most Pseudomonas, the root-associated bacterium Pseudomonas stutzeri A1501 fixes nitrogen after the horizontal acquisition of a nitrogen-fixing (nif) island. A genome-wide search for small noncoding RNAs (ncRNAs) in P. stutzeri A1501 identified the novel P. stutzeri-specific ncRNA NfiS in the core genome, whose synthesis was significantly induced under nitrogen fixation or sorbitol stress conditions. The expression of NfiS was RNA chaperone Hfq-dependent and activated by the sigma factor RpoN/global nitrogen activator NtrC/nif-specific activator NifA regulatory cascade. The nfiS-deficient mutant displayed reduced nitrogenase activity, as well as increased sensitivity to multiple stresses, such as osmotic and oxidative stresses. Secondary structure prediction and complementation studies confirmed that a stem-loop structure was essential for NfiS to regulate the nitrogenase gene nifK mRNA synthesis and thus nitrogenase activity. Microscale thermophoresis and physiological analysis showed that NfiS directly pairs with nifK mRNA and ultimately enhances nitrogenase activity by increasing the translation efficiency and the half-life of nifK mRNA. Our data also suggest structural and functional divergence of NfiS evolution in diazotrophic and nondiazotrophic backgrounds. It is proposed that NfiS was recruited by nifK mRNA as a novel regulator to integrate the horizontally acquired nif island into host global networks. PMID- 27407148 TI - DNA damage tolerance pathway involving DNA polymerase iota and the tumor suppressor p53 regulates DNA replication fork progression. AB - DNA damage tolerance facilitates the progression of replication forks that have encountered obstacles on the template strands. It involves either translesion DNA synthesis initiated by proliferating cell nuclear antigen monoubiquitination or less well-characterized fork reversal and template switch mechanisms. Herein, we characterize a novel tolerance pathway requiring the tumor suppressor p53, the translesion polymerase iota (POLiota), the ubiquitin ligase Rad5-related helicase like transcription factor (HLTF), and the SWI/SNF catalytic subunit (SNF2) translocase zinc finger ran-binding domain containing 3 (ZRANB3). This novel p53 activity is lost in the exonuclease-deficient but transcriptionally active p53(H115N) mutant. Wild-type p53, but not p53(H115N), associates with POLiota in vivo. Strikingly, the concerted action of p53 and POLiota decelerates nascent DNA elongation and promotes HLTF/ZRANB3-dependent recombination during unperturbed DNA replication. Particularly after cross-linker-induced replication stress, p53 and POLiota also act together to promote meiotic recombination enzyme 11 (MRE11) dependent accumulation of (phospho-)replication protein A (RPA)-coated ssDNA. These results implicate a direct role of p53 in the processing of replication forks encountering obstacles on the template strand. Our findings define an unprecedented function of p53 and POLiota in the DNA damage response to endogenous or exogenous replication stress. PMID- 27407150 TI - Reply to Giner-Sorolla: Relationships between inequality and air rage are robust to additional specifications. PMID- 27407149 TI - COP1 is required for UV-B-induced nuclear accumulation of the UVR8 photoreceptor. AB - The UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) promotes UV-B acclimation and tolerance in Arabidopsis thaliana UVR8 localizes to both cytosol and nucleus, but its main activity is assumed to be nuclear. UV-B photoreception stimulates nuclear accumulation of UVR8 in a presently unknown manner. Here, we show that CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) is required for UV-B-induced nuclear accumulation of UVR8, but bypassing the COP1 requirement for UVR8 nuclear accumulation did not rescue the cop1 mutant UV-B phenotype. Using a glucocorticoid receptor (GR)-based fusion protein system to conditionally localize GR-UVR8 to the nucleus, we have demonstrated that both photoactivation and nuclear localization of UVR8 are required for UV-B-induced photomorphogenic responses. In contrast, there was no UV-B response when UV-B-activated UVR8 was artificially retained in the cytosol. In agreement with a predominantly nuclear activity, constitutively active UVR8(W285A) accumulated in the nucleus also in the absence of UV-B. Furthermore, GR-COP1 expression lines suggested that UV-B activated UVR8 can be coimported into the nucleus by COP1. Our data strongly support localization of UVR8 signaling in the nucleus and a dual role for COP1 in the regulation of UV-B-induced UVR8 nuclear accumulation and in UVR8-mediated UV B signaling. PMID- 27407151 TI - Linear controls are not enough to account for multiplicative confound effects on air rage. PMID- 27407152 TI - Reply to Lenz et al.: Quantifying the smallest microplastics is the challenge for a comprehensive view of their environmental impacts. PMID- 27407153 TI - Microplastic exposure studies should be environmentally realistic. PMID- 27407154 TI - Treatment of Stage IIIA Non-Small-Cell Lung Cancer: A Concise Review for the Practicing Oncologist. AB - Stage IIIA non-small-cell lung cancer occurs in a heterogenous group of patients for whom the best treatment is multimodality therapy with chemotherapy, radiation, and surgery in a select group of individuals. This clinical review intends to answer the most common questions that clinicians face in the decision about the best management in this group. PMID- 27407155 TI - Multidisciplinary Treatment of Stage IIIA Non-Small-Cell Lung Cancer. PMID- 27407156 TI - Treatment of Stage IIIA Non-Small-Cell Lung Cancer: Charting the Next Steps. PMID- 27407157 TI - Allogeneic Hematopoietic Stem-Cell Transplantation for Myelofibrosis: A Practical Review. AB - Myelofibrosis is a myeloproliferative neoplasm with cardinal features of extramedullary hematopoiesis, hepatosplenomegaly, cytopenias, and constitutional symptoms that result in shortened survival and leukemic transformation. It is a disease predominantly of the elderly, and currently available therapies only offer symptom control without curative benefit or ability to alter disease progression. Allogeneic hematopoietic stem-cell transplant (HSCT) is the only potentially curative intervention; however, this is only feasible in younger and medically fit patients and selectively offered to those with high-risk disease. Despite ongoing advancements, HSCT is associated with substantial morbidity and mortality, and the determination of which patients with myelofibrosis are ideal candidates and the selection of the opportune moment to proceed with transplantation remains challenging. This review summarizes our current recommendations for the role of and indications for HSCT in myelofibrosis. PMID- 27407158 TI - Outcome Improvement After Allogeneic Stem-Cell Transplantation in Myelofibrosis. PMID- 27407159 TI - Allogeneic Hematopoietic Stem-Cell Transplantation in Myelofibrosis: Key Messages for Clinical Practice in the Era of Janus Kinase 1/2 Inhibitors. PMID- 27407160 TI - Recent Insights and Advances in the Management of Merkel Cell Carcinoma. AB - Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy with a propensity for recurrence and a poor prognosis. Incidence of MCC is on the rise and is known to increase with advanced age, immunosuppression, and UV exposure. Merkel cell polyomavirus is implicated in the pathogenesis of virus-positive MCC and accounts for 80% of MCCs in the northern hemisphere and 25% in southern latitudes. In contrast, tumorigenesis of virus-negative MCC is linked to UV-induced DNA damage. Interplay between ubiquitous Merkel cell polyomavirus skin infections that commonly occur in healthy skin and other established risk factors, such as immunosuppression and UV exposure, remains poorly understood. Surgery and radiotherapy achieves excellent locoregional control; however, invariably, a significant proportion of patients develop disseminated disease that is incurable. Chemotherapy offers a high response rate for metastatic disease, but responses are short-lived and the impact on survival is not established. Recent advances in our understanding of the genetic landscape and immunobiology of MCC has led to investigation of novel treatments, including immune checkpoint inhibitors, which are likely to rapidly transform the way we manage these patients. We review epidemiologic, clinical, and histopathologic features of MCC; describe recent insights in MCC biology; and discuss novel therapeutic approaches. PMID- 27407161 TI - Importance of Sentinel Lymph Node Biopsy in Merkel Cell Carcinoma. PMID- 27407162 TI - Merkel Cell Carcinoma: An Unusually Immunogenic Cancer Proves Ripe for Immune Therapy. PMID- 27407163 TI - Osseous Sarcoidosis Mimicking Metastatic Cancer on Positron Emission Tomography. PMID- 27407164 TI - Structural insights into the interaction of p97 N-terminus domain and VBM in rhomboid protease, RHBDL4. AB - RHBDL4 is an active rhomboid that specifically recognizes and cleaves atypical, positively charged transmembrane endoplasmic reticulum-associated degradation (ERAD) substrates. Interaction of valosin-containing protein (p97/VCP) and RHBDL4 is crucial to retrotranslocate polyubiquitinated substrates for ERAD pathway. Here, we report the first complex structure of VCP-binding motif (VBM) with p97 N terminal domain (p97N) at 1.88 A resolution. Consistent with p97 adaptor proteins including p47-ubiquitin regulatory X (UBX), gp78-VCP-interacting motif (VIM), OTU1-UBX-like element, and FAF1-UBX, RHBDL4 VBM also binds at the interface between the two lobes of p97N. Notably, the RF residues in VBM are involved in the interaction with p97N, showing a similar interaction pattern with that of FPR signature motif in the UBX domain, although the directionality is opposite. Comparison of VBM interaction with VIM of gp78, another alpha-helical motif that interacts with p97N, revealed that the helix direction is inversed. Nevertheless, the conserved arginine residues in both motifs participate in the majority of the interface via extensive hydrogen bonds and ionic interactions with p97N. We identified novel VBM-binding mode to p97N that involves a combination of two types of p97-cofactor specificities observed in the UBX and VIM interactions. This highlights the induced fit model of p97N interdomain cleft upon cofactor binding to form stable p97-cofactor complexes. Our mutational and biochemical analyses in defining the specific interaction between VBM and p97N have elucidated the importance of the highly conserved VBM, applicable to other VBM containing proteins. We also showed that RHBDL4, ubiquitins, and p97 co-operate for efficient substrate dislocation. PMID- 27407166 TI - Toxicity-Related Factors Associated With Use of Services Among Community Oncology Patients. AB - PURPOSE: Community oncology practices frequently manage chemotherapy-associated toxicities, which may disrupt treatment, impair quality of life, and induce unplanned service use. We sought to understand the patterns and correlates of unplanned health care service use among patients receiving first-cycle chemotherapy at five community-based ambulatory oncology practices. PATIENTS AND METHODS: A survey study examined the dichotomous outcome of unplanned service use, defined as oncologist visits, emergency department visits, and hospitalizations, resulting from toxicity-related factors. Newly diagnosed patients with breast, lung, head and neck, or colorectal cancer or non-Hodgkin lymphoma were recruited during the first chemotherapy cycle. Before beginning the second cycle of chemotherapy, patients completed a questionnaire that measured unplanned service use and overall distress, plus severity of nausea, vomiting, diarrhea, constipation, mouth sores, intravenous catheter problems, pain, fever and chills, extremity edema, and dyspnea on a 5-point scale (1, did not experience; 5, disabling). Medical record reviews captured chemotherapy doses, comorbid conditions, and supportive care interventions. Mixed-effects logistic regression was used to identify factors associated with unplanned service use, with random effects specified for each clinic. RESULTS: Among 106 patients (white, 98%; female, 74.5%; mean age +/- standard deviation, 60 +/- 11 years), frequently reported toxicities were pain, nausea, diarrhea, and constipation. Thirty-six patients (34%) reported unplanned service use: 29% reported oncologist visits, 14% reported emergency department visits, and 8% reported hospitalizations. Factors significantly associated with unplanned service use were high patient-reported distress and receipt of colony-stimulating factor. CONCLUSION: Service use resulting from toxicity-related factors occurs frequently in community oncology settings. Monitoring toxicity patterns and outcomes can inform proactive symptom management approaches to reduce toxicity burden between scheduled visits. PMID- 27407167 TI - Nonadherence to Oral Medications for Chronic Conditions in Breast Cancer Survivors. AB - PURPOSE: Nonadherence to oral endocrine therapy is common among women with breast cancer (BC). Less is known about nonadherence to medications for other chronic conditions among survivors of BC. METHODS: We used the MarketScan Database to identify women older than 18 years who had nonmetastatic BC diagnosed between January 1, 2009, and December 31, 2013. Prescriptions were identified for the following six non-cancer-related conditions: hypertension, thyroid disease, hyperlipidemia, gastroesophageal reflux disease, diabetes, and osteoporosis. The study period was defined as 1 year before BC diagnosis (index date) through 1.5 years after the index date, with a 6-month washout period after the index data to control for adherence during the preoperative period and during chemotherapy if necessary. Adherence was defined as a medication possession ratio >= 80%. Change in adherence was defined as a 20% decrease in the medication possession ratio from the time before diagnosis compared with after treatment. Factors associated with change in adherence were evaluated in multivariable logistic models. RESULTS: Among 36,149 patients diagnosed with BC, the average adherence to these medications before BC was 91.4%. However, after BC treatment, adherence decreased to 77.9% (P < .001). Looking at drugs for each condition, nonadherence ranged from 15.6% to 38% (P < .001). Factors associated with an increase in nonadherence included older age, insurance type, number of medications, and comorbid conditions. CONCLUSION: Decreased adherence to medications for chronic diseases was found in the first year after breast cancer treatment. Breast cancer survivors may need additional interventions to improve their adherence to their medications for chronic conditions. PMID- 27407165 TI - An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour. AB - Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks alpha1-antitrypsin (alpha1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered beta sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the beta-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence alpha1-AT polymerisation. PMID- 27407168 TI - Dysregulation of intracellular trafficking and endosomal sorting in Alzheimer's disease: controversies and unanswered questions. AB - Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques in the brain consisting of an aggregated form of amyloid beta-peptide (Abeta) derived from sequential amyloidogenic processing of the amyloid precursor protein (APP) by membrane-bound proteases beta-site APP-cleaving enzyme 1 (BACE1) and gamma-secretase. The initial processing of APP by BACE1 is re-gulated by intracellular sorting events of the enzyme, which is a prime target for therapeutic intervention. GWAS (genome-wide sequencing studies) have identified several AD-susceptibility genes that are associated with the regulation of membrane trafficking, and substantial evidence now indicates that AD is likely to arise from defective membrane trafficking in either or both of the secretory and endocytic pathways. Considerable progress has been made in defining the intracellular trafficking pathways of BACE1 and APP and the sorting signals of these membrane proteins that define their itineraries. In this review we highlight recent advances in understanding the regulation of the intracellular sorting of BACE1 and APP, discuss how dysregulation of these trafficking events may lead to enhanced generation of the neurotoxic Abeta products in AD and highlight the unresolved questions in the field. PMID- 27407169 TI - Protein lysine methylation by seven-beta-strand methyltransferases. AB - Methylation of biomolecules is a frequent biochemical reaction within the cell, and a plethora of highly specific methyltransferases (MTases) catalyse the transfer of a methyl group from S-adenosylmethionine (AdoMet) to various substrates. The posttranslational methylation of lysine residues, catalysed by numerous lysine (K)-specific protein MTases (KMTs), is a very common and important protein modification, which recently has been subject to intense studies, particularly in the case of histone proteins. The majority of KMTs belong to a class of MTases that share a defining 'SET domain', and these enzymes mostly target lysines in the flexible tails of histones. However, the so-called seven-beta-strand (7BS) MTases, characterized by a twisted beta-sheet structure and certain conserved sequence motifs, represent the largest MTase class, and these enzymes methylate a wide range of substrates, including small metabolites, lipids, nucleic acids and proteins. Until recently, the histone-specific Dot1/DOT1L was the only identified eukaryotic 7BS KMT. However, a number of novel 7BS KMTs have now been discovered, and, in particular, several recently characterized human and yeast members of MTase family 16 (MTF16) have been found to methylate lysines in non-histone proteins. Here, we review the status and recent progress on the 7BS KMTs, and discuss these enzymes at the levels of sequence/structure, catalytic mechanism, substrate recognition and biological significance. PMID- 27407170 TI - The ADAMTS hyalectanase family: biological insights from diverse species. AB - The a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs (ADAMTS) family of metzincins are complex secreted proteins that have diverse functions during development. The hyalectanases (ADAMTS1, 4, 5, 8, 9, 15 and 20) are a subset of this family that have enzymatic activity against hyalectan proteoglycans, the processing of which has important implications during development. This review explores the evolution, expression and developmental functions of the ADAMTS family, focusing on the ADAMTS hyalectanases and their substrates in diverse species. This review gives an overview of how the family and their substrates evolved from non-vertebrates to mammals, the expression of the hyalectanases and substrates in different species and their functions during development, and how these functions are conserved across species. PMID- 27407171 TI - Structure and function of carbonic anhydrases. AB - Carbonic anhydrases (CAs, EC 4.2.1.1) catalyse the interconversion between CO2 and bicarbonate as well as other hydrolytic reactions. Among the six genetic families known to date, the alpha-, beta-, gamma-, delta-, zeta- and eta-CAs, detailed kinetic and X-ray crystallographic studies have allowed a deep understanding of the structure-function relationship in this superfamily of proteins. A metal hydroxide nucleophilic species of the enzyme, and a unique active site architecture, with half of it hydrophilic and the opposing part hydrophobic, allow these enzymes to act as some of the most effective catalysts known in Nature. The CA activation and inhibition mechanisms are also known in detail, with a large number of new inhibitor classes being described in the last years. Apart from the zinc binders, some classes of inhibitors anchor to the metal ion coordinated nucleophile, others occlude the entrance of the active site cavity and more recently, compounds binding outside the active site were described. CA inhibition has therapeutic applications for drugs acting as diuretics, antiepileptics, antiglaucoma, antiobesity and antitumour agents. Targeting such enzymes from pathogens may lead to novel anti-infectives. Successful structure-based drug design campaigns allowed the discovery of highly isoform selective CA inhibitors (CAIs), which may lead to a new generation of drugs targeting these widespread enzymes. The use of CAs in CO2 capture processes for mitigating the global temperature rise has also been investigated more recently. PMID- 27407172 TI - Correction: Chemical ubiquitination for decrypting a cellular code. PMID- 27407173 TI - A meta-analysis of copper level and risk of preeclampsia: evidence from 12 publications. AB - The association between copper level and risk of preeclampsia (PE) has produced inconsistent results. Thus, a meta-analysis was conducted to summarize the evidence from epidemiological studies for copper level and PE risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge up to April 2016. Standardized mean difference (SMD) was performed to combine the results. Random-effect model (REM) was used. Publication bias was estimated using Egger's regression asymmetry test. Twelve articles (10 case-control studies and 2 cross sectional studies) involving 442 PE cases and 463 health controls were included in this meta-analysis. Our pooled results suggested that PE patients had a higher copper level compared with healthy pregnancy controls [summary SMD=0.69, 95% CI: 0.54-0.84, I(2)=96.7%; P<0.001]. The association was also significant in Asian population [SMD=0.73, 95% CI=0.57-0.90, I(2)=97.3%] and European populations [SMD=0.50, 95% CI=0.14-0.86, I(2)=58.9%]. After conducting the subgroup analysis and sensitive analysis, the results showed consistent significant association with the one based on all studies. No publication biases were found. Our analysis indicated that plasma or serum copper level in PE patients was significantly higher than that in healthy pregnancy women. PMID- 27407174 TI - Comparison of interleukin-10 and interleukin-13 in cord blood of infants born by vaginal delivery and caesarean. AB - BACKGROUND: The present study assessed the levels of IL-13 and IL-10 in umbilical cord blood of infants born through normal vaginal delivery and infants born with cesarean section. METHODS: This pilot study was performed on 42 neonates born at Rasool-e-Akram hospital between May 2013 and May 2014 categorized into two groups born by vaginal delivery (n = 21) and those who born by cesarean section (n = 21). RESULTS: No difference was observed between the two groups with normal vaginal delivery and cesarean delivery in the level of IL-13 in umbilical cord blood (1.42 +/- 0.23 versus 1.40 +/- 0.22, respectively, p = 0.785). The mean level of IL-10 in umbilical cord blood in the group with vaginal delivery was 6.35 +/- 2.54 and in another group with cesarean section was 5.69 +/- 2.42 with no significant difference (p = 0.393). According to the multivariate linear regression analyses, no difference was found between the two groups of the mode of delivery in the level of IL-10 (beta = -0.454, SE = 0.802, p = 0.575) and also in the level of IL-13 (beta = 0.012, SE = 0.076, p = 0.877). None of the indicators including gestational age, mother's age, sex of neonate, number of live births, history of abortion, and number of parity could predict increased level of the interleukins in umbilical cord blood. CONCLUSION: Mode of delivery may not be an indicator for altering cord blood levels of IL-13 and IL-10. PMID- 27407175 TI - G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice. AB - Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10-12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G 1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI. PMID- 27407176 TI - Central pontine myelinolysis secondary to hyperglycaemia. AB - Central pontine myelinolysis is characterised by focal osmotic demyelination within the pons. Its clinical presentation varies, but may include acute paralysis, dysarthria and dysphagia. The cause is traditionally associated with overzealous correction of hyponatraemia in patients who are malnourished, alcoholic or chronically ill. However, it may develop in the context of normal serum sodium, since rapid gradient shifts in brainstem osmolalities can occur in other ways. We present an unusual example of central pontine myelinolysis caused by osmotic shifts secondary to hyperglycaemia in a person with type 1 diabetes mellitus and with consistently normal serum sodium concentrations. PMID- 27407177 TI - Non-mydriatic fundus photography: a practical review for the neurologist. AB - Declining proficiency in direct ophthalmoscopy by non-ophthalmologists has spurred a search for alternative methods of ocular fundus examination. Recent technological advances have improved the ease of use and quality of non-mydriatic fundus photography, increasing its suitability for clinical care. As the availability of this technology continues to improve, neurologists will need to be familiar with its advantages, limitations and potential applications in the clinical care of patients with neurological conditions. PMID- 27407178 TI - E-Cigarettes: The Science Behind the Smoke and Mirrors. AB - E-cigarettes are a diverse set of devices that are designed for pulmonary delivery of nicotine through an aerosol, usually consisting of propylene glycol, nicotine, and flavorings. The devices heat the nicotine solution using a battery powered circuit and deliver the resulting vapor into the proximal airways and lung. Although the current devices on the market appear to be safer than smoking combusted tobacco, they have their own inherent risks, which remain poorly characterized due to widespread product variability. Despite rising use throughout the United States, predominantly by smokers, limited evidence exists for their efficacy in smoking cessation. Pending regulation by the FDA will enforce limited disclosures on the industry but will not directly impact safety or efficacy. Meanwhile, respiratory health practitioners will need to tailor their discussions with patients, taking into account the broad range of existing effective smoking cessation techniques, including pharmaceutical nicotine replacement therapy. PMID- 27407179 TI - Pulmonary Rehabilitation in COPD According to Global Initiative for Chronic Obstructive Lung Disease Categories. AB - BACKGROUND: Pulmonary rehabilitation (PR) programs are a mainstay for treatment in COPD. Lung function impairment alone does not predict beneficial effects of PR. The new COPD categories take into account assessment of symptoms, such as dyspnea and exacerbations, which may be important indications for PR. This study evaluates the effect of PR on exercise capacity, symptoms, and health status in different COPD categories. METHODS: Subjects with COPD referred for PR were classified into COPD categories A, B, C, and D. Exercise capacity (6-min walk distance [6MWD] and constant work rate at 80% of peak work rate), symptoms (Mahler's index), and health status (St George Respiratory Questionnaire) were compared before and after PR programs for each COPD category. Changes were analyzed using generalized estimating equations and logistic regression models. RESULTS: One hundred sixty-seven subjects were included (COPD categories A [16%], B [12%], C [31%], and D [41%]). Groups were homogeneous in age, body mass index, smoking pack-years, and comorbidities. Significant improvements in all outcomes were found after adjusting for COPD categories, age, sex, body mass index, and COPD-specific comorbidity index. All COPD categories improved exercise capacity (6MWD and constant work rate). Categories A and C had more pronounced improvements in 6MWD than categories B and D. Symptoms (Mahler's index) also improved significantly in categories A and C, whereas change was not significant in categories B and D. Global health status (St George Respiratory Questionnaire) improved significantly in all COPD categories. Despite these differences, the odds of achieving a minimum clinically important difference in each outcome were similar and without statistical significance for the A, B, and C categories when compared with D. CONCLUSIONS: This study demonstrates that patients in all COPD categories may improve exercise capacity, symptoms, and health status with PR programs, and COPD categories alone may not be sufficient to discriminate which patients may benefit most from them. PMID- 27407181 TI - Functional characteristics, nutritional value and industrial applications of Madhuca longifolia seeds: an overview. AB - New sustainable edible oil sources are desired to achieve supply chain flexibility and cost saving opportunities. Non-traditional fruit seeds are being considered because their constituents have unique chemical properties and may augment the supply of nutritional and functional products. Madhuca longifolia Syn. M. indica (Sapotaceae) is an important economic tree growing throughout the subtropical region of the Indo-Pak subcontinent. Information concerning the exact composition of mahua butter (known also as mowrah butter) from fruit-seeds of buttercup or Madhuca tree is scare. Few studies investigated mahua butter for its composition, nutritional value, biological activities and antioxidative properties. In consideration of potential utilization, detailed knowledge on the chemical composition, nutritional value and industrial applications of mahua butter is of major importance. The diversity of applications to which mahua butter can be put gives this substance great industrial importance. This review summarizes recent knowledge on bioactive compounds, functional properties as well as food and non-food industrial applications of mahua butter. Graphical abstract?. PMID- 27407180 TI - The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion. AB - Stress adaptation plays a pivotal role in biological processes and requires tight regulation of gene expression. In this study, we explored the effect of cellular stress on mRNA polyadenylation and investigated the implications of regulated polyadenylation site usage on mammalian gene expression. High-confidence polyadenylation site mapping combined with global pre-mRNA and mRNA expression profiling revealed that stress induces an accumulation of genes with differentially expressed polyadenylated mRNA isoforms in human cells. Specifically, stress provokes a global trend in polyadenylation site usage toward decreased utilization of promoter-proximal poly(A) sites in introns or ORFs and increased utilization of promoter-distal polyadenylation sites in intergenic regions. This extensively affects gene expression beyond regulating mRNA abundance by changing mRNA length and by altering the configuration of open reading frames. Our study highlights the impact of post-transcriptional mechanisms on stress-dependent gene regulation and reveals the differential expression of alternatively polyadenylated transcripts as a common stress-induced mechanism in mammalian cells. PMID- 27407182 TI - Intellectual assets management and transfer in food science sector in Indian research and development organizations. AB - In recent years, the food science sector has gained importance since the society is focusing on high-quality and safety foods. With a specific end goal to meet this societal need, the research and development organizations in India have adopted innovative technical and research processes, which gave more accentuation on intellectual assessment in food processing industry. The global Intellectual Property regime in food science sector had witnessed an increment in the number of patents filed and granted during 2006-2010. Ever since there has been a gradual increase in the number of patents applied mainly in food processing industries by research organizations related to food sciences, for example, those working under the aegis of ICAR and CSIR in India. In this study, a review has been done on the intellectual assets generated by ICAR and other national research organizations in India, in the food science sector. Emphasis has been given on the global relevance of these assets, modes of IP protection and technology transfer mechanisms followed by different public and private organizations. PMID- 27407184 TI - Promising features of mango (Mangifera indica L.) kernel oil: a review. AB - Mango kernel contains about 15 % good quality edible oil, that is comparable to soybean and cottonseed, which contain about 18-20 % oil. Mango kernel oil (MKO) has lower free fatty acids, carotenoid content and peroxide value, and is usually used without any processing, which is otherwise mandatory for commercial vegetable oils. Palmitic, stearic and oleic acids are the major fatty acids, triglyceride composition and fatty acid profile suggest wide range of trans free options. With 32-36 degrees C melting point, MKO is solid at room temperature, thus, does not require partial hydrogenation for application in foods. MKO can be used as an alternative of cocoa butter, which is used in chocolates and confectionaries. Total phenolic contents and induction period of MKO is greater than many commercial vegetable oils; thus, it can be used as an alternative of synthetic antioxidants for the preservation of fats and oils. Mangiferin, chlorogenic acid, quercetin and caffeic acid are the major phenolic compounds present in MKO. Functional properties of MKO can be further improved through fractionation, transesterification and interesterification for increased industrial applications. PMID- 27407183 TI - Potentiality of botanical agents for the management of post harvest insects of maize: a review. AB - Natural products derived from plants are emerging as potent biorational alternatives to synthetic insecticides for the integrated management of post harvest insects of maize. In this paper, effectiveness of botanicals including plant extracts, essential oils, their isolated pure compounds, plant based nano formulations and their mode of action against storage insects have been reviewed with special reference to maize. Plant based insecticides found to be the most promising means of controlling storage insects of maize in an eco friendly and sustainable manner. This article also throws light on the commercialization of botanicals, their limitations, challenges and future trends of storage insect management. PMID- 27407185 TI - Trends and advances in food analysis by real-time polymerase chain reaction. AB - Analyses to ensure food safety and quality are more relevant now because of rapid changes in the quantity, diversity and mobility of food. Food-contamination must be determined to maintain health and up-hold laws, as well as for ethical and cultural concerns. Real-time polymerase chain reaction (RT-PCR), a rapid and inexpensive quantitative method to detect the presence of targeted DNA-segments in samples, helps in determining both accidental and intentional adulterations of foods by biological contaminants. This review presents recent developments in theory, techniques, and applications of RT-PCR in food analyses, RT-PCR addresses the limitations of traditional food analyses in terms of sensitivity, range of analytes, multiplexing ability, cost, time, and point-of-care applications. A range of targets, including species of plants or animals which are used as food ingredients, food-borne bacteria or viruses, genetically modified organisms, and allergens, even in highly processed foods can be identified by RT-PCR, even at very low concentrations. Microfluidic RT-PCR eliminates the separate sample processing step to create opportunities for point-of-care analyses. We also cover the challenges related to using RT-PCR for food analyses, such as the need to further improve sample handling. PMID- 27407186 TI - Biogenic amines in seafood: a review. AB - The biogenic amines are low molecular weight organic bases present normally in the body with biological activity influencing important physiological functions. The physiological functions of these molecules are achieved by very low concentrations in the tissues. However, significantly high amounts of biogenic amines are produced during processing and storage of seafood as a result of microbial contamination and inadequate storage conditions. Microorganisms having decarboxylase enzyme activity convert amino acids to their respective biogenic amines. Biogenic amines in seafood have been implicated as a major causative agent of food borne illness, where intoxication results from the ingestion of foods containing higher amount of biogenic amines. Hence its identification, quantitation and awareness of this food borne toxin are important in relation to food safety and spoilage. The aim of this paper is to review the basic concepts of seafood quality and safety in relation to biogenic amines along with its control measures and future areas for research. PMID- 27407187 TI - Development and performance evaluation of frustum cone shaped churn for small scale production of butter. AB - The present research was intended to develop a small scale butter churn and its performance by altering churning temperature and churn speed during butter making. In the present study, the cream was churned at different temperatures (8, 10 and 12 degrees C) and churn speeds (35, 60 and 85 rpm). The optimum parameters of churning time (40 min), moisture content (16 %) and overrun (19.42 %) were obtained when cream was churned at churning temperature of 10 degrees C and churn speed of 60 rpm. Using appropriate conditions of churning temperature and churn speed, high quality butter can be produced at cottage scale. PMID- 27407188 TI - Effect of Gallic acid on mechanical and water barrier properties of zein-oleic acid composite films. AB - In this study, the effect of gallic acid on mechanical and water barrier properties of zein-oleic acid 0-4 % composite films was investigated. Molecular weight distribution analysis was carried out to confirm gallic acid induced cross linking through change in molecular weight in fraction containing zein proteins. Results revealed that gallic acid treatment increased tensile strength from 17.9 MPa to 26.0 MPa, decreased water vapour permeability from 0.60 (g mm m(-2) h(-1) kPa(-1)) to 0.41 (g mm m(-2) h(-1) kPa(-1)), increased solubility from 6.3 % to 10.2 % and marginally increased elongation at break from 3.7 % to 4.2 % in zein films only. However, gallic acid treatment in zein-oleic composite films did not significantly influence mechanical and water barrier properties and in most instances irrespective of oleic acid concentration, the properties were negatively affected. Results from scanning electron microscopy showed that both gallic acid treated and untreated zein films and composite films containing 3 % oleic acid had a compact and homogeneous structure while those containing 4 % oleic acid had inhomogeneous structure. The findings have demonstrated that gallic acid treatment can significantly improve mechanical and water barrier properties especially in zein films only as opposed to when used in composite films using zein and oleic acid. PMID- 27407189 TI - Development and shelf-life evaluation of tomato-mushroom mixed ketchup. AB - This study reports on the possibility or suitability of ketchup preparation using mushroom pulp with tomato pulp. The pulp was extracted from mature and sound tomatoes and button mushroom (Agaricus bisporus L.) and subsequently used for preparation of Tomato-Mushroom ketchup. Different combinations of mushroom pulp with tomato pulp were made for ketchup preparation. The ketchup prepared with 50 % tomato pulp and 50 % mushroom pulp obtained highest organoleptic scores and was preferred than other treatments. The organoleptic score for ketch-up prepared by 100 % mushroom pulp was lowest. There was significant increase in protein, crude fibre and ash content whereas TSS, acidity, total sugars and vitamin C decreased significantly with increase in level of mushroom pulp. TSS increased significantly from 27.32 degrees B to 31.03 degrees B during storage for 12 months. Whereas acidity value decreased from 2.22 % to 2.10 %. There was significant decrease in total sugars and increase in reducing sugars during storage at room temperature (RT). Vitamin C content also decreased significantly during storage. All these physico-chemical changes were less at refrigerated temperature (RFT) conditions. The mean value for overall sensory score decreased from 7.80 on zero days to 7.11 at RT and from 7.80 to 7.47 at RFT after 12 months of storage. A significant increase in total plate count of ketch-up was observed during storage at room as well as at refrigerated temperature conditions. However this change was more at RT than RFT. PMID- 27407190 TI - Evaluation of antioxidant activity of loquat fruit (Eriobotrya japonica lindl.) skin and the feasibility of their application to improve the oxidative stability of soybean oil. AB - The effects of ultrasound-assisted, supercritical CO2 and solvent extraction techniques on antioxidant activity of loqua (Eriobotrya japonica Lindl.) skin extract in oxidation stability of soybean oil was evaluated. The antioxidant efficacy of extracts was determined using 2, 2-diphenyl-1-picrylhydrazyl (DPPH(*)) radical scavenging capacity, beta-carotene/linoleic acid, and Rancimat test system. Results showed that solvent extract of loquat fruit skin at 400 ppm had the highest antioxidant activity compared to ultrasound-assisted and supercritical CO2 extracts. Further, solvent extraction was the most effective method for extraction of phenolic compounds. Protective effects of extracts in stabilization of soybean oil during both frying and storage conditions were tested and compared to tert-butyl hydroquinone (TBHQ) by measuring their peroxide value, free fatty acids, conjugated dienes and trienes value. During frying process solvent extract of skin at 400 ppm (SOEA) exhibited stronger antioxidant activity in oil compared to other oil samples, but this antioxidant potential was lower than TBHQ in storage conditions. Present study showed that loquat fruit skin is a good source of natural antioxidant compounds, and has the potential to be used as a substitute for synthetic antioxidants in vegetable oils. PMID- 27407191 TI - A gradient based facile HPLC method for simultaneous estimation of antioxidants extracted from tea powder. AB - A new simple, rapid and precise RP-HPLC method was developed for the extraction and quantitative estimation of caffeine (C), (-)-epigallocatechin gallate (EGCG), (+)-catechin(Ct), (-)-epicatechin(EC), and (-)-epicatechin gallate (ECG) (collectively named as Tea Powder Bioactives TPBAs) extracted from tea powder using different ratios of ethanol: water. The simultaneous determination of TPBAs was performed using the UV spectrophotometric method which employs the absorbance at 205 nm (lambdamax of caffeine and polyphenols). This method is a gradient based HPLC method with a flow rate of 0.8 mL/min using Inertsil ODS 100 * 4.6 mm, 3 MUm column with methanol and ammonium dihydrogen phosphate (pH-2.8) as mobile phase. The method was validated in terms of specificity, precision, linearity, accuracy, limit of quantification (LOQ), and limit of detection (LOD). The linearity of the proposed method was investigated for concentration ranging between 0.5-60 MUg/mL with regression co-efficient, R(2) = 0.999-1.0. This method estimates all the TPBAs simultaneously with enhanced precision and linearity as per the ICH guidelines. Also, to confirm the individual TPBA, the antioxidant property of the each TPBA was analyzed which was commensurate with that of the previous reports. PMID- 27407192 TI - Argentinian pistachio oil and flour: a potential novel approach of pistachio nut utilization. AB - In order to searching a potential novel approach to pistachio utilization, the chemical and nutritional quality of oil and flour from natural, roasted, and salted roasted pistachios from Argentinian cultivars were evaluated. The pistachio oil has high contents of oleic and linoleic acid (53.5 - 55.3, 29 - 31.4 relative abundance, respectively), tocopherols (896 - 916 MUg/g oil), carotenoids (48 - 56 MUg/g oil) and chlorophylls (41 - 70 MUg/g oil), being a good source for commercial edible oil production. The processing conditions did not affect significantly the fatty acid and minor composition of pistachio oil samples. The content of total phenolic (TP) and flavonoids (FL) was not significantly modified by the roasting process, whereas free radical scavenging (DPPH radical) and antioxidant power decreased in a 20% approximately. Furthermore, salted roasted pistachio flour (SRPF) showed a significant decrease in TP and FL content in comparison to others samples. The phenolic profile of pistachio flours evaluated by LC-ESI-QTOF-MS. The major compounds identified were (+)-catechin (38 - 65.6 MUg/g PF d.w.), gallic acid (23 - 36 MUg/g PF d.w.) and cyanidin-3-O-galactoside (21 - 23 MUg/g PF d.w.). The treatments effects on the phenolics constituents of pistachio flour. Roasting caused a significant reduction of some phenolics, gallic acid and (+)- catechin, and increased others, naringenin and luteolin. Salting and roasting of pistachio increased garlic acid and naringenin content. PMID- 27407193 TI - Culture media optimization of Porphyridium purpureum: production potential of biomass, total lipids, arachidonic and eicosapentaenoic acid. AB - Porphyridium purpureum a red marine microalga is known for phycobiliproteins (PB), polyunsaturated fatty acids and sulphated exopolysaccharides. In the present study, effects of media constituents for the production of different polyunsaturated fatty acids from P. purpureum were considered using a response surface methodology (RSM). A second order polynomial was used to predict the response functions in terms of the independent variables such as the concentrations of sodium chloride, magnesium sulphate, sodium nitrate and potassium dihydrogen phosphate. The response functions were production of biomass yield, total lipid and polyunsaturated fatty acids like arachidonic acid (AA 20:4) and eicosapentaenoic acid (EPA 20:5). Results corroborated that maximum Biomass (0.95 gL(-1)) yield was at the concentrations of sodium chloride (14.89 gL(-1)), magnesium sulfate (3.93 gL(-1)) and sodium nitrate (0.96 gL(-1)) and potassium dihydrogen phosphate (0.09 gL(-1)). Optimum total lipid (17.9 % w/w) and EPA (34.6 % w/w) content was at the concentrations of sodium chloride (29.98 gL(-1)), magnesium sulfate (9.34 gL(-1)) and sodium nitrate (1.86 gL(-1)). Variation in concentration of potassium dihydrogen phosphate for both lipid (0.01gL(-1)) and EPA content (0.20 gL(-1)) was observed. The optimum conditions for biomass, total lipid, AA and EPA varied indicating their batch mode of growth and interaction effect of the salt. PMID- 27407194 TI - Nutritional composition and antioxidant activity of Spanish and Virginia groundnuts (Arachis hypogaea L.): a comparative study. AB - Kernels of sixty groundnut genotypes comprising thirty each of Spanish and Virginia groups were characterized and compared for the content of oil, protein, phenols and antioxidant activity along with their fatty acid and sugars profiles. The antioxidant activity for Virginia genotypes was ranged from 12.5 to 16.5 MUM Trolox equivalent activity for Spanish genotypes ranged from 6.8-15.2 MUM. Amongst Virginia types, the highest oleic acid/linoleic acid (O/L) ratio of 2.38 was observed for NRCG 12312 while from Spanish group the highest O/L ratio of 1.24 was observed for NRCG 12731. The sucrose content for Virginia genotypes ranged from 38.5 to 69.0 mg/g while it was 27.9 to 53.3 mg/g for Spanish genotypes. Average myo-inositol content was higher for Spanish genotypes (0.8-2.1 mg/g) compared to Virginia (0.4-1.8 mg/g) while the reverse was true for stachayose content (Spanish: 3.5-7.9 mg/g; Virginia: 4.6-10.3 mg/g). Thus, Virginia genotypes could be preferred to Spanish genotypes for better oil stability and antioxidant activity. PMID- 27407195 TI - The effect of flow rate at different pressures and temperatures on cocoa butter extracted from cocoa nib using supercritical carbon dioxide. AB - The effects of flow rate, different pressures and temperatures on cocoa butter extracted from cocoa nib using supercritical carbon dioxide (scCO2) were investigated. The yield was analyzed for total fat content, triacylglycerol (TG) profile, and fatty acid (FA) profile. Extractions were carried out at pressures of 20 and 35 MPa, temperatures of 50 and 60 degrees C, and CO2 flow rates of 0.5, 1, 2, 4 mL min(-1). The result shows that the yield of cocoa butter extract increased with increasing pressure, temperature, and flow rate and the optimum conditions for the maximum cocoa butter extraction were 35 MPa, 60 degrees C and 2 mL min(-1), repectively. TGs and FAs were found to be similar in composition to those of cocoa butter obtained by conventional methods. The lower molecular weight TGs and FAs showed higher selectivity compared to higher molecular weight TGs and FAs. PMID- 27407196 TI - Cloning and characterization of mersacidin like bacteriocin from Bacillus licheniformis MKU3 in Escherichia coli. AB - A putative gene encoding mersacidin like lantibiotic bacteriocin (lanA) was identified in Bacillus licheniformis genome. The lanA open reading frame codes for 74 amino acids with calculated isoelectric point of 6.7 and molecular mass of 8.2 kDa. The lanA gene was amplified from B. licheniformis MKU3, cloned in pQE30 vector and overexpressed in Escherichia coli M15. The recombinant peptide was purified to homogeneity using Ni-NTA chromatography and the SDS-PAGE analysis of the purified peptide revealed it to be a monomer with molecular mass of ~8.5 kDa. The purified bacteriocin showed wide spectrum activity against gram-positive pathogens. The peptide was found to be stable under in wide range of pH, temperature tolerant and resistant to the proteolytic enzymes. The stable nature of the bacteriocin to high temperature and resistant to various chemicals it also exhibited antimicrobial activity against food-borne pathogens make this bacteriocin as potent attractive antimicrobial agent in food products. PMID- 27407197 TI - Antioxidant components and physico-chemical characteristics of jamun powder supplemented pear juice. AB - Studies were conducted to develop jamun powder supplemented pear juice. Two drying methods (Hot air cabinet drying and freeze drying) were used to prepare jamun pulp powder. Jamun powder was then blended with pear juice at 1, 2, 3, 4 and 5 % levels for preparation of jamun powder supplemented pear juice. Among the drying methods used, freeze dried powder retained better bioactive compounds and possessed higher antioxidant activity as compared to hot air dried jamun powder. Analysis of color properties (L*, a*, b*) revealed lower L*, b* values and higher a* values with progression of supplementation levels indicating decreased brightness of product. Pear juice supplemented with 4 % jamun powder received highest overall acceptability scores and was chosen for development of final product. Physico-chemical characteristics of control pear juice did not vary much from when compared to jamun powder supplemented pear juice. Bioactive components mainly total phenols enhanced (9.24 % higher) with addition of jamun powder in pear juice. Addition of anthocyanins from jamun powder to pear juice upon blending improved antioxidant activity of the final product. Supplemented pear juice had 18.13 % higher antioxidant activity than pear juice without supplementation. Storage period of 6 months resulted in significant (p < 0.05) decrease of bioactive compounds and antioxidant activity in jamun powder supplemented pear juice. PMID- 27407198 TI - Energetic and exergetic performance analysis and modeling of drying kinetics of kiwi slices. AB - This work focused on the effects of the moisture content, slices thickness and microwave power on aspects of energy and exergy, drying kinetics, moisture diffusivity, activation energy, and modeling of the thin layer drying of kiwi slices. Results showed that energy and exergy efficiency increased with increasing microwave power and decreasing slice thickness while values of energy efficiency (15.15-32.27 %) were higher than exergy efficiency (11.35-24.68 %). Also, these parameters decreased with a decrease in moisture content. Specific energy consumption varied from 7.79 to 10.02, 8.59 to 10.77 and 9.57 to16.20 to MJ/kg water evaporated for 3, 6 and 9 mm, respectively. The values of exergy loss were found to be in the range of 5.90 and 14.39 MJ/kg water and decreased as the microwave power increased and slice thickness decreased. Effective diffusivity increased with decreasing moisture content and increasing microwave power and slice thickness. Average effective moisture diffusivity of kiwi slices changes between 1.47 * 10(-9) and 39.29 * 10(-9) m(2)/s within the given variables range. Activation energy (17.96-21.38 W/g) showed a significant dependence on the moisture content. Although the Midilli model showed the best fit, Page's model was selected, since it had almost a similar performance but the model is simpler with two parameters instead of four. PMID- 27407199 TI - Study of sorption behavior, shelf life and colour kinetics of vacuum puffed honey powder at accelerated storage conditions. AB - In the study, the storage life of vacuum puffed honey powder at accelerated storage environment (90 % relative humidity and 36 degrees C) was computed by determining the sticky-point moisture content as the critical parameter of the honey powder. The value of monolayer moisture content in the GAB model was calculated to be 0.081 kg water/kg dry solids by fitting water activity and moisture sorption data. Shelf life of the honey powder was predicted to be 222 days when the powder was packaged in aluminum foil-laminated polyethylene pouches with permeability value of 5.427X10(-8) kg/m(2)//day/Pa. Actual shelf life of honey powder was experimentally determined as 189 days and analysis of mean relative percent derivation modulus (Rd) and root mean square (RMS) established the accuracy and acceptability of the technique for the prediction of shelf life of honey powder. Overall colour deviation pattern followed first order reaction kinetics with rate constant (k1) as 0.037 day(-1). This study revealed overall colour difference of 18.1 till the end of shelf life with drastic change during initial storage period. PMID- 27407200 TI - Effect of ultrasonic pretreatment on physicochemical characteristics and rheological properties of soy protein/sugar Maillard reaction products. AB - Maillard reaction products (MRPs) of soybean protein isolate (SPI) and sugars (glucose and maltose) were prepared by heating in the aqueous dispersion at 95 degrees C for 15 min with ultrasonic pretreatment (ultrasonic power of 200 W) for 20 min. Effect of ultrasonic pretreatment on physicochemical characteristics and rheological properties of SPI/sugar MRPs was investigated. SPI/sugar MRPs prepared with ultrasonic pretreatment had higher degree of glycation (DG), lower browning and less compact tertiary conformation than that with non-ultrasonic pretreatment. Surface hydrophobicity (H0), particle size and rheological properties were measured by fluorescence spectrophotometry, laser particle size analysis and dynamic oscillatory rheometry, respectively. Glycation reduced H0 and particle size as well as weaken the gel network formed by the acidification of GDL. However, ultrasound increased H0 and decreased particle size. This is desirable for the formation of acid-induced gel structure. The ultrasonic pretreatments reduced/eliminate the weakening effect of glycation on the gel network of SPI/sugar MRPs, and even improved the gel properties. PMID- 27407201 TI - A comparative study on the effectiveness of ozonated water and peracetic acid in the storability of packaged fresh-cut melon. AB - Ozonated water and peracetic acid were tested as sanitizers to enhance the storability of fresh-cut melon cubes. Sanitizers were also combined with suitable packaging materials (polypropylene and polylactic acid based plastic films). Fresh-cut melon cubes were stored at 4 degrees C for up to 7 days. Ozonated water and peracetic acid treatments were given by dipping cubes into 0.8 ppm O3 and 100 ppm Tsunami 100TM solutions, respectively, for 3 min. Both sanitizers exhibited efficiency in reducing the total microbial counts on melon cubes (< 2 log CFU g(-1)). Respiratory activity and ethylene production were both affected by the interaction between the sanitizer and the packaging used. Carbon dioxide and oxygen reached 9.89 kPa and 12.20 kPa partial pressures, respectively, using peracetic acid treatment in combination with polypropylene film packaging, consequently developing off-odors starting from day 3. Strong color changes were noted in cubes stored in polylactic acid packaging after 7 days of storage, affecting the sensory quality of the melon cubes. Sensory evaluation (overall visual quality) indicated loss in flavor in the polypropylene packaging. The overall visual quality started to decline on 3rd day because of the development of translucency.Overall, the use of ozone in combination with polypropylene packaging provided the best solution to maintain the quality of melon cubes for up to 5 days of storage at 4 degrees C. PMID- 27407202 TI - Fermentation induced changes in bioactive properties of wine from Phyllanthus with respect to atherosclerosis. AB - Wine was prepared from three varieties of Phyllanthus viz., P. emblica (wild and cultivated) and P. acidus. Among the wines prepared, cultivated Emblica wine had the highest total phenolic (11.02 MUg gallic acid equivalent/ml) and flavonoid (59.46 MUg quercetin equivalent/ml) content. Further gallic acid, syringic acid, protocatechuic acid and caffeic acid were present in higher amounts in wine from the cultivated variety compared to other wines. HPLC analysis showed that in juice of the cultivated variety, gallic acid and coumaric acid were found in higher amounts than that in the corresponding wine. Antioxidant assays, LDL oxidation prevention, foam cell prevention and nitrite scavenging activities (cell lines) were found to be highest in cultivated Emblica juice and wine with an activity of 15 MUg/ml and 14 MUg/ml (nitrite assay) and 108.649 MUg ascorbic acid equivalent/mg and 321.622 MUg ascorbic acid equivalent /mg (total antioxidant capacity) respectively. CD36 expression was reduced and ABCA1 expression was increased to the highest extent by the cultivated Emblica wine and juice. Further, antioxidant activity was seen to increase during the course of fermentation. Sensory analysis showed that cultivated Emblica wine was sweeter compared to the other wines. PMID- 27407203 TI - Enzymatic changes in plum (Prunus salicina Lindl.) subjected to some chemical treatments and cold storage. AB - The objective of the present work is to see the effect of different chemical treatments on pectin methylesterase (PME) activity and softening of the fruits. Purple plums (cv. Satluj) fruits were harvested at colour break stage and treated for 5- minutes in aqueous solutions of salicylic acid at 138, 276 and 414 ppm, Ascorbic acid at 10,000, 20,000 and 30,000 ppm, and Gibberelic acid at 20, 40 and 60 ppm. For control the fruits were dipped in distilled water. Treated fruits were stored at low temperature conditions for 40 days. Physico chemical characteristics and PME activity were determined at 10 day interval. The colour of the fruits improved with respect to a* and b* values progressively throughout the storage, whereas, fruit firmness decreased. Total sugars and PME activity increased before showing a declining trend. Pre-storage application of salicylic acid (414 ppm) significantly delayed colour development. Fruits treated with salicylic acid (414 ppm) retained highest firmness, total sugars and PME activity at the end of storage. PMID- 27407204 TI - Combined infrared-vacuum drying of pumpkin slices. AB - Infrared-vacuum dehydration characteristics of pumpkin (Cucurbita moschata) were evaluated in a combined dryer system. The effects of drying parameters, infrared radiation power (204-272 W), system pressure (5-15 kPa), slice thickness (5 and 7 mm) and time (0-220 min) on the drying kinetics and characteristics of pumpkin slices were investigated. The vacuum pressure, lamp power and slice had significant effect on the drying kinetics and various qualities of the dried pumpkin. Moisture ratios were fitted to 10 different mathematical equations using nonlinear regression analysis. The quadratic equation satisfactorily described the drying behavior of pumpkin slices with the highest r value and the lowest SE values. The effective moisture diffusivity increased with power and ranged between 0.71 and 2.86 * 10(-9) m(2)/s. With increasing in infrared radiation power from 204 to 272 W, beta-carotene content of dried pumpkins decreased from 30.04 to 24.55 mg/100 g. The rise in infrared power has a negative effect on the color changes (DeltaE). The optimum condition was determined as power, 238W, pressure, 5 kPa and slice thickness, 5mm. These conditions resulted into dried pumpkin slices with maximum B-carotene retention. PMID- 27407205 TI - Influence of three different concentration techniques on evaporation rate, color and phenolics content of blueberry juice. AB - The present study was undertaken to assess the effects of three different concentration processes open-pan, rotary vacuum evaporator and microwave heating on evaporation rate, the color and phenolics content of blueberry juice. Kinetics model study for changes in soluble solids content ( degrees Brix), color parameters and phenolics content during evaporation was also performed. The final juice concentration of 65 degrees Brix was achieved in 12, 15, 45 and 77 min, for microwave at 250 and 200 W, rotary vacuum and open-pan evaporation processes, respectively. Color changes associated with heat treatment were monitored using Hunter colorimeter (L*, a* and b*). All Hunter color parameters decreased with time and dependently studied concentration techniques caused color degradation. It was observed that the severity of color loss was higher in open-pan technique than the others. Evaporation also affected total phenolics content in blueberry juice. Total phenolics loss during concentration was highest in open-pan technique (36.54 %) and lowest in microwave heating at 200 W (34.20 %). So, the use of microwave technique could be advantageous in food industry because of production of blueberry juice concentrate with a better quality and short time of operation. A first-order kinetics model was applied to modeling changes in soluble solids content. A zero-order kinetics model was used to modeling changes in color parameters and phenolics content. PMID- 27407206 TI - Spray dried melon seed milk powder: physical, rheological and sensory properties. AB - Melon seed milk (MSM) powder was produced by aiming to get alternative vegetable milk from crushed Kirkagac (Cucumis melo subsp. melo cv. Kirkagac) and Cesme (C. melo subsp. melo cv. Cesme) type melon seeds. MSM was converted to powder form via spray dryer at inlet air temperature of 150 degrees C, air flow rate of 473 l . h(-1), aspiration ratio of 24 m(3) . h(-1)and feed flow rate of 8 ml . min( 1) in order to extend the shelf life and usage area. The moisture content and water activity of samples changed in range of 2.1 to 2.4 % and 0.260 to 0.310, respectively. Bulk densities and the tapped densities of powders were ranged from 340 to 360 kg . m(-3) and 730 and 740 kg . m(-3). MSM powders showed poor flow behavior as determined from Carr Index. The particle densities of powders ranged between and 1069 kg . m(-3). Wettability time of powders was found as 7 s. The Bingham model was the best model fitted to rheological data of MSM beverages. Sensory evaluation test results showed that, the beverage obtained from reconstituted Kirkagac powder achieved the highest score by panelists. PMID- 27407207 TI - Impact of pH and temperature on the colour and betalain content of Colombian yellow pitaya peel (Selenicereus megalanthus). AB - The effects of different pHs (4, 5 and 6), temperatures (4, 20 and 80 degrees C) and storage (up to 12 days) on differential tristimulus colorimetry and betalain content related to the colour of yellow pitaya (Selenicereus megalanthus) have been investigated. The peel of the yellow pitaya was extracted with different solvents to see its colorant capacity. Highly-acidic extracts (pH 4) showed the lowest betalain content, chroma (C* ab = 60 against 70) and the yellow component of the colour (b*). Storage temperature manifested a great influence on CIELAB parameters when yellow pitaya peel was added to highly-acidic foodstuffs, with a tendency towards red hues (h ab , from 100 degrees to 85 degrees ) and remarkable changes on lightness (L*, from 90 to 75) as temperature increased. However, low-acidic extracts (pH 5 and 6) were superior from a colour stability standpoint, not being influential the temperature of storage. All colour changes according to pH and temperature were visually appreciable by human eyes (?E* ab > 3). New opportunities for diversification of colorant market could be possible by employing yellow pitaya peel as natural resource. PMID- 27407208 TI - Effect of hydrocolloids on the energy consumption and quality of frozen noodles. AB - Effects of hydrocolloids such as Sodium polyacrylate, xanthan gum and sodium alginate on the energy consumption and quality of frozen cooked noodles were investigated. Results showed that gelatinization temperature (GT) shortened significantly and texture properties (hardness, firmness, break strength) of frozen cooked noodle were significantly improved by adding different hydrocolloid additives (P < 0.05). Nevertheless, there were no significant differences of glass-transition temperature between hydrocolloid fortified and non fortified frozen cooked noodles. Moreover, the hydrocolloids improved quality of cooked noodle and increased energy consumption, however, xanthan gum showed the best results. The optimized constituents were: sodium polyacrylate 0.13 %, xanthan gum 0.86 %, sodium alginate 0.18 % with predicted sensory scores of 90.30. The study showed that hydrocolloids could be used as modifying agents in frozen cooked noodle process. PMID- 27407209 TI - Fortification of dahi (Indian yoghurt) with omega-3 fatty acids using microencapsulated flaxseed oil microcapsules. AB - The objective of the study was to develop and characterize omega-3 dahi (Indian yoghurt) through fortification of microencapsulated flaxseed oil powder (MFOP). Four different formulations of MFOP were fortified in dahi @ 1, 2 and 3 % levels and the level of addition was optimized on the basis of sensory scores. Dahi fortified at 2 % level was observed comparable to control, which was further studied for titratable acidity, syneresis, firmness, stickiness, oxidative stability (peroxide value), alpha-linolenic acid (ALA, omega-3) content and sensory attributes during 15d of storage. MFOP fortified dahi showed significantly (p < 0.05) higher acidity and percent syneresis after 12d of storage. However, peroxide value remained well below (~0.41) to the maximum permissible limit (5 meq peroxides/kg oil) prescribed by Codex Alimentarius Commission (1999). Gas-liquid chromatography profile showed ~21 % decrease in ALA content in fortified dahi after 15d of storage. Overall, it can be concluded that flaxseed oil microcapsules could be successfully incorporated in dahi; which could serve as a potential delivery system of omega-3 fatty acids. PMID- 27407210 TI - Effect of grain moisture content during milling on pasting profile and functional properties of amaranth fractions. AB - Evaluation of functional properties of milled fractions of grain amaranth may be useful to decide the end uses of the grain. Hence, pasting profiles of amaranth fractions obtained by milling the grains at different moisture contents were studied in relation with their starch profile and also with their swelling power and solubility indices. It was observed that, for flour fraction, the viscosity parameters were lowest at 14-16 % moisture content. Swelling power and solubility indices of the samples varied as a function of grain moisture content. The middling fraction also showed similar pasting pattern with the variation of grain moisture content. The seed coat fractions showed higher gelatinization temperature compared to that of fine flour and middling fractions. However, starch content of the fine seed coat fraction was comparable with that of the flour and middling fractions. The coarse seed coat fraction showed lower viscosity parameters than the other samples. Viscosity parameters correlated well among themselves while, they did not show significant correlation with the starch content. However, the viscosity parameters showed negative correlation with the soluble amylose content. The study revealed that, the fractions obtained by milling the grains at different moisture content show differential pasting profiles and functional properties. PMID- 27407211 TI - Effect of different cooking methods on structure and quality of industrially frozen carrots. AB - The effect of boiling, steaming and microwaving on microstructure, texture and colour of raw and industrially frozen carrots was investigated. The raw carrots, after cooking, showed dehydrated and separated cells with swollen walls. The carrots subjected to blanching, freezing and followed by frozen storage exhibited marked tissue damages indicating deep oriented fissures. Cooking caused cellular dehydration and separation in the tissue, with the same intensity between raw and frozen carrots and independently from the cooking treatment applied. Among different cooking methods, microwaving showed better retention of the initial texture and colour quality for both raw and frozen carrots. On the other hand, the steamed carrots revealed the highest degree of softening and colour differences from the control for both raw and frozen carrots, despite the worst tissue conditions were observed for the boiled carrots. PMID- 27407212 TI - Effect of different doses of nitrogen on protein profiling, pasting and quality attributes of rice from different cultivars. AB - Effect of different level (60, 120 and 180 kg N/ha) of nitrogen (N) application on protein profiling, pasting and cooking quality characteristics of milled rice from different paddy cultivars was evaluated. N dose showed positive correlation with protein content and negative correlation with L*, whiteness and amylose content. N application significantly affected the protein profile, textural and pasting properties of different cultivars. All the cultivars expect PR120 and PAU201, showed an increase in the amount of accumulation of 60 kDa polypeptide with increase in N application. Accumulation of prolamines (16 and 14 kDa) and polypeptides of 38 and 35 kDa increased in all the cultivars. Size exclusion chromatography revealed decrease in low molecular weight subunits and increase in medium molecular weight subunits in all the cultivars upon N application. However, high molecular weight subunits increased in IET21214 and decreased in PR120 and PAU20 upon N application. N application resulted in increase in glutelins and decrease in peak and breakdown viscosity. PAU201 and PR120 showed lower AAC due to low accumulation of 60 kDa granule-bound starch synthase (GBSS), in response to N application. Gumminess and hardness of cooked rice increased with the increase in N dose and the increase was significant at 60 kg N/ha. PMID- 27407213 TI - Probiotic attributes of indigenous Lactobacillus spp. isolated from traditional fermented foods and beverages of north-western Himalayas using in vitro screening and principal component analysis. AB - The present research was designed to explore indigenous probiotic Lactic acid bacteria from traditional fermented foods and beverages of North-western Himalayas for their probiotic potential. It was achieved through a step-by step approach focused on the technological characterization, evaluation of the probiotic traits and adherence ability. Fifty one LAB isolates from traditional fermented foods and beverages were initially screened for their technological properties and among them twenty isolates were selected. These isolates were further characterized and identified using 16S rRNA gene sequencing as Lactobacillus brevis (7 isolates), Lactobacillus casei (5), Lactobacillus paracasei (2), Lactobacillus buchneri (1), Lactobacillus plantarum (1) and Lactobacillus sp. (3). Identified isolates were evaluated by in vitro methods including survival in gastrointestinal tract, antibiotic susceptibility, antimicrobial activity, cell surface characteristics, exopolysacharride production and haemolytic activity. The results of these experiments were used as input data for Principal Component Analysis; thus, to select the most promising probiotic isolates. Three isolates (L. brevis PLA2, L. paracasei PLA8 and L. brevis PLA16) were found to be most technological relevant and promising probiotic candidates in comparison to commercial probiotic strains. L. brevis PLA2 was selected as best isolate with probiotic potential by in vitro adherence to the human intestinal HT-29 cell line. PMID- 27407214 TI - Antioxidant activities of a peptide derived from chicken dark meat. AB - Antioxidant activities against hypochlorite ions and peroxyl radicals of a chicken dark meat hydrolysate digested with pepsin were examined with the myoglobin method based on the structure change of myoglobin due to redox reaction with reactive oxygen species (ROS). A peptide that showed strong antioxidant activity against the peroxyl radical was isolated from the hydrolysate using HPLC equipped with a hydrophobic-interacting column. The sequence of the first five amino acid residues of the peptide was determined as YASGR (Tyr-Ala-Ser-Gly-Arg), and this sequence matched with the amino acid residues 143-147 of chicken beta actin (GenBank: CAA25004.1). The synthetic peptide YASGR showed very high antioxidant activity against the peroxyl radical. Antioxidant activities of the free amino acids, confirmed that the tyrosine residue of this peptide was possibly responsible for antioxidant activity. PMID- 27407215 TI - Effect of gelatinized-retrograded and extruded starches on characteristics of cookies, muffins and noodles. AB - The effect of substitution of wheat flour with gelatinized-retrograded starch (GRS) and extruded starch (ES) at 10 and 20 % levels on characteristics of cookies, muffins and noodles was evaluated. Cookies made by substitution of flour with GRS or ES were lighter in color, showed higher spread ratio and resistant starch (RS) content. Muffins made by substitution of flour with GRS or ES were lighter in color, showed less height, specific volume and gas cells and higher RS content. Muffins containing GRS were less firm while those made by incorporating ES showed higher firmness than those made without substitution. Noodles made with substitution of flour with GRS or ES showed higher RS content and reduced water uptake, gruel solid loss, hardness and adhesiveness. Cookies and noodles prepared with and without substitution of flour with GRS or ES did not show any significant differences in terms of overall acceptability scores. PMID- 27407216 TI - A new measurement approach of ionizing radiation in irradiated trout (Oncorhynchus mykiss) by Randomly Polymorphic DNA-Polymerase Chain Reaction. AB - Trout (Oncorhynchus mykiss) were irradiated at doses of 0.250, 0.500, 1, 3, 5, 7 and 9 kGy in gamma cell. DNAs were extracted from the irradiated samples before and after storage. 1ERP primers were designed, and RAPD-PCR (Randomly Polymorphic DNA-Polymerase Chain Reaction) was applied to make randomly amplifications on the DNA of the irradiated samples. Agarose gel profiles of irradiated fish were obtained to determine change of band profiles. In addition, DNA fragmentation occurring in each dose was determined by comet assay for the verification of methodology developed in this study. The molecular methodology was developed to estimate ionizing radiation (IR) level in irradiated fish. This methodology allows the analysis of the trout irradiated up to the dose limit of around 0.5 kGy and stored for a period of three months. PMID- 27407217 TI - Standardization of the conditions for extraction of polyphenols from pomegranate peel. AB - Pomegranate (Punica granatum) peel possess higher antioxidant activity than the edible portion. Efforts were made to extract dry peel powder at room temperature (28-30 degrees C) using combination of water and ethanol (EtOH, a green combination) and standardize the factors that may affect the extraction efficiency. The storage stability of the extract has been studied for >100 days at room temperature (28-30 degrees C), 4, 0 and -80 degrees C. The extract quality was monitored by measuring the radical scavenging activity (RSA) by diphenyl picrylhydrazyl (DPPH) method, total polyphenol content and by estimating the contents of punicalagins and ellagic acid, the two major ellagitannins present in the peel. The standardized conditions for extraction were found to be; Water and EtOH in 1:1 (v/v) ratio, duration of 24-48 h, ratio of 1:10 for solid to solvent and particle size in the range of 100-400 MU. Consecutive extraction of the peel powder did neither improve the yield nor polyphenol content, hence single extraction was adopted. The extract stored at room temperature for 110 days resulted in 13.2 % loss of polyphenol content followed by 8.9, 2.8, 27.5 and 14.1 % loss in Punicalgin A, B, Ellagic acid and RSA content, respectively. PMID- 27407218 TI - Early diagnosis of rheumatic diseases: an evaluation of the present situation and proposed changes. AB - Musculoskeletal pain is a very common complaint, affecting 30-40% of the European population. It is estimated that approximately 400,000 Poles suffer from inflammatory rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, and a vast majority of those affected are working-age individuals. Patients with suspected arthritis require prompt diagnosis and treatment, as any delays may result in irreversible joint destruction and disability. Currently in Poland, the lag time between the onset of symptoms and diagnosis is, on average, as much as 35 weeks. In this paper, we review the current state of specialist rheumatology care in Poland and propose a reorganised care model that includes early diagnosis of inflammatory arthritis. The main goal we wish to achieve with our reorganised model is to enhance access to outpatient specialist rheumatology care for patients with suspected arthritis. We believe that our model should make it possible to considerably reduce the lag time between GP referral and the diagnosis and treatment by a rheumatologist to as little as 3 to 4 weeks. This article provides a proposal of changes that would achieve this goal and is a summary of the report published by the Institute of Rheumatology in September 2014. PMID- 27407219 TI - Cytokine profiles in axial spondyloarthritis. AB - OBJECTIVES: Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL 23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. MATERIAL AND METHODS: Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient's medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. RESULTS: In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 +/-184.0 pg/ml vs. 14.0 +/-17.1 pg/ml, p < 0.0001 and 45.5 +/-71.9 pg/ml vs. 18.4 +/-14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 +/-246.9 pg/ml vs. 99.9 +/-105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 +/-8.50 pg/ml vs. 2.04 +/-2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. CONCLUSIONS: We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more severe course of aSpA. PMID- 27407220 TI - Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases. AB - OBJECTIVES: Connective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient's clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. MATERIAL AND METHODS: Data from 24 patients with CTD treated with tumor necrosis factor-alpha-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. RESULTS: Patient median height, measured as the change in height standard deviation score, was 0.36 +/-1.07 at disease onset and -0.13 +/-1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 +/-0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. CONCLUSIONS: In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses. PMID- 27407221 TI - The effect of leptin on the respiratory burst of human neutrophils cultured in synovial fluid. AB - OBJECTIVES: Leptin is a hormone responsible for nutritional status and immune competence coordination. In rheumatoid arthritis (RA) increased leptin levels were observed in both serum and synovial fluid. Its influence on development of the disease still remains unclear. So far, research on leptin's influence on the emission of reactive oxygen intermediates (ROI) measured with chemiluminescence (CL) has provided unclear and contradictory results. In this study, we evaluated the influence of leptin on oxidative activity of neutrophils isolated from blood of healthy volunteers and cultured in different amounts of synovial fluid (SF) from patients with RA. MATERIAL AND METHODS: Neutrophils' oxidative metabolism was measured by two types of CL. The first one, luminol-dependent CL (CL-lum), allows one to determine phagocytic activity and the level of ROI generated in a myeloperoxidase-dependent manner. The second method used was lucigenin-dependent CL (CL-luc), which monitors ROI production dependent on the NADPH oxidase enzyme complex located in the cell membranes of neutrophils and enables one to determine the scope of extracellular ROI emission. RESULTS: Neutrophils stimulated by opsonized zymosan show a decrease in the level of CL-lum, proportional to the increasing concentration of both SF and serum collected from healthy donors. The observed effect of decreased CL-lum may, therefore, be dependent on the physical conditions (viscosity of fluids used). None of these experiments showed any effect of leptin on the level of CL-lum. CONCLUSIONS: The present study showed that leptin does not affect the level of any of the CL types in inactive neutrophils incubated in normal serum, and it does not affect the level of oxidative activity in resting neutrophils incubated with SF. However, leptin influences extracellular ROI emission (measured by CL-luc). Leptin reduces extracellular emission of ROI, and this effect is dependent on concentration and duration of exposure to leptin. PMID- 27407222 TI - Current nutritional status of patients with rheumatic diseases in the population of Poland. AB - THE AIM OF THE STUDY: The aim of the study was to evaluate the current state of nutrition of patients with rheumatic diseases in the Polish population. MATERIAL AND METHODS: An anonymous questionnaire study was carried out among the patients of the Institute of Rheumatology in Warsaw in the fourth quarter of 2012. Five hundred questionnaires were distributed, and 397 questionnaires were collected and accepted for further analysis (response rate = 79%). RESULTS: Overweight or obesity was present in more than half (53%) of the patients (overweight in 30.5% of respondents, obesity in 22.6%). Among obese subjects, 43% of men and 37% of women in the study think that their diet is correct. Sixty-eight percent of respondents declared that they do not follow any special diet and only 18% declared that they follow a diet with a reduced quantity of monosaccharides (no sweets). A milk-free diet was followed by 7% of respondents, a meat-free diet by 6%, and a fruit-and-vegetable diet by 5%. Dietary supplements were regularly used by 26.7% of respondents, whereas 33.8% did not use them at all. The average assessment of physical aptitude (Health Assessment Questionnaire - HAQ) in the group of respondents was 0.71. No statistically significant differences were found between higher level of disability (e.g. HAQ >= 1) and the type of diet followed (p = 0.678) or body mass index (BMI) value (p = 0.864) in relation to persons with the value of HAQ < 1. CONCLUSIONS: More than half of patients suffering from rheumatic diseases are overweight or obese, which corresponds to the body weight profile of the population of Poland. Most patients diagnosed with rheumatic diseases do not follow any special diet. In spite of the frequent use of dietary supplements, the patients do not consult a doctor or a dietician about it. The type of diet and BMI value do not differ according to the level of disability. PMID- 27407223 TI - Total ankle replacement - surgical treatment and rehabilitation. AB - Functions of the ankle joint are closely connected with the gait and ability to maintain an upright position. Degenerative lesions of the joint directly contribute to postural disorders and greatly restrict propulsion of the foot, thus leading to abnormal gait. Development of total ankle replacement is connected with the use of the method as an efficient treatment of joint injuries and continuation of achievements in hip and knee surgery. The total ankle replacement technique was introduced as an alternative to arthrodesis, i.e. surgical fixation, which made it possible to preserve joint mobility and to improve gait. Total ankle replacement is indicated in post-traumatic degenerative joint disease and joint destruction secondary to rheumatoid arthritis. In this paper, total ankle replacement and various types of currently used endoprostheses are discussed. The authors also describe principles of early postoperative rehabilitation as well as rehabilitation in the outpatient setting. PMID- 27407224 TI - The role of physiological elements in the future therapies of rheumatoid arthritis. II. The relevance of energy redistribution in the process of chronic inflammation. AB - The reasons for development of chronic inflammation are complex and not fully understood. One of the factors affecting the prolongation of inflammation is changes in cell metabolism, occurring at the center of the inflammatory process. In chronic inflammation there is an imbalance between the processes of storage and consumption of energy reserves. Hypoxia that is a consequence of edema results in transition of white blood cells to anaerobic metabolism. Neutrophils, lymphocytes and macrophages produce active oxygen metabolites which on one hand facilitate the elimination of pathogens, and on the other hand, can cause damage to healthy cells located in the inflamed tissue. In this paper, we discuss the importance of disturbed redistribution of energy as one of the main reasons for transformation of the acute inflammatory process into the chronic one. PMID- 27407225 TI - Post-Lyme disease syndrome. AB - About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well. PMID- 27407226 TI - Heart failure with complete recovery in a patient with systemic lupus erythematosus. AB - We report the case of a 43-year-old female patient who was admitted to the Cardiology Department from the Rheumatology Clinic where she was being treated for multi-organ serositis, fatigue and mild dyspnoea on exertion. The patient had a known medical history of systemic lupus erythematosus (SLE). Following extensive evaluation with blood tests for immunological and viral culprits, cardiac ultrasound, chest and abdominal computed tomography (CT) and heart magnetic resonance imaging (MRI), the diagnosis of effusive constrictive pericarditis secondary to her SLE was made. Treatment with beta-blockers, diuretics and corticosteroids was given with excellent results, and one year post discharge the patient remains asymptomatic. Systemic lupus erythematosus patients often manifest cardiac complications such as pericarditis. The practising physician should always bear in mind this possibility when treating such patients. PMID- 27407227 TI - Coronary artery disease is a significant cause of morbidity and premature death in patients with systemic lupus erythematosus. PMID- 27407228 TI - Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression. AB - OBJECTIVES: Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. MATERIAL AND METHODS: The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases 37 girls (74%) and 13 boys (26%), aged 1.5-17.5 years - during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children - 28 girls (56%) and 22 boys (44%) aged 2-17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0-1-6 months schedule. The antibody concentration of >= 10 mIU/ml in patients is regarded as protective. RESULTS: No protective antibody concentrations were found in 25 cases (50%) in the group of diseased children and only in 2 children in the control group (4%). CONCLUSIONS: The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B. PMID- 27407229 TI - Prevalence of selected organ-specific autoantibodies in rheumatoid arthritis and primary Sjogren's syndrome patients. AB - OBJECTIVES: The aim of the study was to investigate the prevalence of selected organ-specific autoantibodies in rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS) patients, and discuss their clinical significance. MATERIAL AND METHODS: The study included 121 RA and 30 pSS patients. Sera were tested for the presence of autoantibodies to thyroid peroxidase (anti-TPO), thyroglobulin (anti TG), TSH receptor (TRAbs), mitochondrial antigen M2 (AMA-M2-3E) and gliadin analogous fusion peptides (anti-GAF(3X)) using the ELISA method. Non-organ specific antibodies were determined: rheumatoid factor in IgM class, anti citrullinated peptide antibodies and antinuclear antibodies. The occurrence of antibodies was also examined with regards to RA activity. RESULTS: The following autoantibodies were detected in RA patients: anti-TPO - 13 (10.7%), anti-TG - 6 (5%), AMA-M2-3E - 3 (2.5%), anti-GAF(3X) - 5 (4.1%). The respective levels of these autoantibodies in pSS patients were 3 (10%), 2 (6.7%), 4 (13.3%) and 2 (6.7%). Polyautoimmunity was confirmed in 34 RA patients (including 20 cases of autoimmune thyroid disease [AITD]) and in 6 pSS patients (6 cases of AITD). When RA patients were divided into anti-TPO positive and anti-TPO negative groups, we found a statistically significant relationship between groups regarding age and hemoglobin concentration. In pSS patients the anti-TPO positive group was less likely to use immunosuppressive drugs as compared with the anti-TPO negative group. Anti-TPO was significantly more frequently detected in RA + AITD vs. RA, RA + SS + AITD vs. RA and in pSS + AITD vs. pSS patients. CONCLUSIONS: Organ specific autoantibodies are relatively frequently observed in patients with RA and pSS. Their presence is connected with the clinical picture of the diseases. PMID- 27407230 TI - Incidence of Chlamydia trachomatis infection in patients with reactive arthritis. AB - OBJECTIVES: The aim of the study was to evaluate the incidence of Chlamydia trachomatis in patients with reactive arthritis (ReA) within the area of the Podlaskie province (north eastern Poland). MATERIAL AND METHODS: The study concerned 323 patients including 132 women and 191 men diagnosed with ReA. The material for C. trachomatis was collected from the urethra in men and the cervical canal in women. Also, every patient was tested for the presence of anti C. trachomatis IgG class antibodies, while 121 individuals were additionally tested for IgA class antibodies. In the direct studies, the direct immunofluorescence (DIF) method or polymerase chain reaction (PCR) was used. The immunoenzymatic method was used to detect anti-C. trachomatis antibodies. The control group in the case of direct studies comprised 125 individuals, while in the case of serology research it included 127 (IgG) and 109 (IgA) persons. RESULTS: Chlamydia trachomatis infection in the urethral and cervical smears was found in 42 patients (13.0%) including 20 women (15.2%) and 22 men (11.5%). In the control group chlamydia was detected in 3 patients (2.4%) including 4% of women and 2% of men. IgA class antibodies were present in 10/121 (8.3%) patients, similarly in women and in men (8.2% and 8.3% respectively). In the control group the specific IgA class antibodies were found in 3/85 patients (3.5%). Anti-C. trachomatis IgG antibodies were found in 70/323 patients (21.7%), similarly in men and women. CONCLUSIONS: Chlamydia trachomatis is a common bacterial factor observed in the genitourinary system of patients with ReA. The outcomes of studies within the Podlaskie province indicate less frequent presence of chlamydial infection compared with Dolnoslaskie province.No correlations between detecting the presence of C. trachomatis in the urogenital tract and the presence of specific antibodies in the serum of ReA patients were observed.Concurrent direct studies of the urogenital tract and a serological blood test increase the chance of detecting C. trachomatis infection. PMID- 27407231 TI - HLA-B27 detection - comparison of genetic sequence-based method and flow cytometry assay. AB - OBJECTIVES: The presence of human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis. HLA-B27 testing is routinely applied in the diagnosis of this disease. The aim of the present study was to compare two methods of HLA-B27 detection - a genetic sequence-based method and a flow cytometry assay. MATERIAL AND METHODS: Peripheral blood was obtained from 300 individuals with suspected spondyloarthropathy. Expression of HLA-B27 on the T cell surface was analysed by flow cytometry assay using GS145.2 monoclonal antibody specific for HLA-B27. DNA was isolated from the whole blood. Genes coding for HLA-B27, -B40 and -B47:01 were detected by polymerase chain reaction using the MW02/MW09 primer pair. Then, positive samples were sequenced in order to discriminate allelic variations of the HLA-B27 gene. Results of sequencing were analysed using Chromas LITE 2.1.1 software, BLAST software and the IMGT/HLA database. Ambiguous samples were additionally analysed by polymerase chain reaction using E91 and E136 primers amplifying a 135-bp fragment of the human HLA B27 gene. RESULTS: Among 300 samples, 76 were HLA-B27-positive on the basis of flow cytometry analysis. Genetic sequence analysis confirmed positivity of 73 from among 76 samples. Two hundred twenty six samples were HLA-B27-negative, whereas the result of one sample analysis was ambiguous. Fifty-three samples were identified as allelic variation 27:05, 19 samples as allelic variation 27:02, and one sample as allelic variation 27:07. CONCLUSIONS: This study shows that the genetic sequence-based method and the flow cytometry assay give consistent results in 99% of cases. The performed genetic analysis proves that the majority of HLA-B27-positive samples belong to the 27:05 allelic variation, which is strongly associated with high risk of ankylosing spondylitis. PMID- 27407232 TI - Changes in the morbidity and costs of systemic lupus erythematosus in Poland in the years 2008-2012. AB - OBJECTIVES: The goal of the article is to present the changes in morbidity and costs of systemic lupus erythematosus (SLE) in Poland in the 2008-2012 period, depending on the province of residence of the patients based on data reported to the public payer - the National Health Fund. MATERIAL AND METHODS: Based on the ICD-10 code and the patient's personal identity number, the number of patients and medical costs (cost of hospitalization, pharmaceutical, medical procedures, dialysis and specialist consultations) were calculated by province (voivodeship) and urban or rural residence. RESULTS: Annually on average in the assessed period in Poland approximately 20 000 patients were diagnosed with SLE. The studied group was dominated by women (they were 5.2 times more numerous). The morbidity rate was 52.183 patients per 100 thousand inhabitants. Most patients were in the age range of 48-56 years. Average annual expenses for this group of patients over the examined period were USD 16,327 million. Two times more was expended on patients inhabiting cities, approximately 4 times more on women. Calculated per patient, the average cost of therapy was USD 810.63. CONCLUSIONS: The population of SLE patients in Poland is highly stable. The results of analysis indicate 1.64 times more frequent occurrence in urban areas, which may be connected with availability of doctors. The SLE treatment costs in Poland are much lower than in other countries, which is related mainly to the fact that therapy with biological drugs is not financed. PMID- 27407233 TI - Raynaud's phenomenon: new aspects of pathogenesis and the role of nailfold videocapillaroscopy. AB - Raynaud's phenomenon (RP) refers to paroxysmal pallor or cyanosis of the digits of the hands or feet and, infrequently, the tips of the nose or ears (acral parts) owing to cold-induced vasoconstriction of the digital arteries, precapillary arterioles, and cutaneous arteriovenous shunts. Raynaud's phenomenon reflects an exaggeration of normal central and local vasomotor responses to cold or emotion. Raynaud's phenomenon has been classified as primary or secondary, depending on whether it occurs as an isolated condition or is associated mainly with a connective tissue disease. Dysregulation of autonomic and sensitive nerve fibers, functional and structural vessel changes, and intravascular alterations can be observed in the pathogenesis of RP. Nailfold videocapillaroscopy (NVC) is the best non-invasive and repetitive diagnostic technique for detecting morpho functional changes in the microcirculation. Nailfold videocapillaroscopy is accepted in early diagnosis and monitoring of primary and secondary RP. PMID- 27407234 TI - U1-RNP and TLR receptors in the pathogenesis of mixed connective tissue diseasePart I. The U1-RNP complex and its biological significance in the pathogenesis of mixed connective tissue disease. AB - Mixed connective tissue disease (MCTD) is a rare autoimmune syndrome, signified by complex interactions between disease-related phenomena, including inflammation, proliferative vascular arteriopathy, thrombotic events and humoral autoimmune processes. It is still controversial whether MCTD is a distinct clinical entity among systemic connective tissue diseases, although several authors consider that it is distinct and underline characteristic, distinct clinical, serological and immunogenetic features. The putative target of autoimmunity in MCTD is U1-RNP, which is a complex of U1-RNA and small nuclear RNP. Both the U1-RNA component and the specific proteins, particularly U1-70K, engage immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. U1-RNA is capable of inducing manifestations consistent with TLR activation. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins. PMID- 27407235 TI - Polymyositis and dermatomyositis as a risk of developing cancer. AB - Polymyositis (PM) is an idiopathic inflammatory myopathy that affects striated muscles. Dermatomyositis (DM) is an idiopathic inflammatory myopathy with presence of skin symptoms. Both are characterized by acute or subacute onset, symmetrical proximal muscle weakness, the presence of mononuclear cell infiltrates of the muscles and increased activity of muscle enzymes. The treatment still remains glucocorticoids and disease-modifying drugs. Symptoms of PM/DM can be a signal of developing cancer. Known risk factors for cancer in patients with PM/DM are older age, male gender, dysphagia, skin necrosis, cutaneous vasculitis, rapid onset of the disease, elevated creatinine kinase (CK) and C reactive protein (CRP), and an increase in the erythrocyte sedimentation rate (ESR). Recently three new myositis-specific autoantibodies (MSA) predicting the risk of cancer have been discovered: melanoma differentiation-associated protein 5 (anti-MDA-5), transcription intermediary factor 1gamma (TIF-1gamma), and nuclear matrix protein NXP-2. PMID- 27407236 TI - Adult-onset Still's disease as a mask of Hodgkin lymphoma. AB - Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied. PMID- 27407237 TI - Predictors of juvenile idiopathic arthritis course. AB - INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases of joints in children with various and often unfavourable prognosis. It is possible to improve the outcome of the disease in patients with JIA by a correct therapeutic choice made at disease onset - one that enables fast achievement of an inactive disease state and remission. The aim of the investigation was to develop a model/application for automatic calculation of risk of treatment-refractory JIA taking into account the combined action of clinical and cytokine factors. MATERIAL AND METHODS: Disease subtype was determined in 105 patients with JIA, as well as the number of poor prognostic factors and disease activity level. Blood serum cytokine levels (IL-1beta, IL-4, IL-6, IL-8, IL-10, IL-17, TNF-alpha, IFN-gamma) and their soluble receptors and agonists - interleukin 1 receptor agonist (IL-1Ra), soluble interleukin 2 receptor (sCD25), interleukin 6 (sIL6R), soluble tumour necrosis factor receptor 1 (sTNFR1) - were determined in these patients using immunoenzymatic laboratory methods. RESULTS: The following prognostic factors were taken into account in the study: JIA subtype, disease activity, presence of clinically unfavourable factors and cytokine characteristics. We determined that systemic subtype of JIA, moderate and high disease activity, presence of factors of poor disease course and sCD25 and IL-6 levels are statistically significant factors of treatment refractory disease course. A Microsoft Excel application was developed for automatic calculation of risk of treatment-refractory JIA in a specific patient based on 10 factors. CONCLUSIONS: Use of an application for automatic calculation of risk of treatment-refractory JIA enables prediction of JIA disease course in patients at disease onset and personalization of the treatment protocol. PMID- 27407238 TI - Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis. AB - INTRODUCTION: Human leukocyte antigen B27 (HLA-B27) is considered as a risk factor for development of juvenile idiopathic arthritis (JIA). The aim of this study was to analyse the prevalence of HLA-B27 antigen in JIA categories and its influence on disease onset and response to conventional therapy. MATERIAL AND METHODS: The retrospective analysis included 461 unselected children with JIA hospitalized in a single reference rheumatology centre between July 2007 and June 2012. The diagnosis was based on criteria by the International League of Association for Rheumatology. HLA-B27 was determined in 387 of all patients (84%) by hybridization of the amplified, labelled product to immobilize it on the microarray probe. RESULTS: HLA-B27 antigen was found in 104 of 383 affected children (27.2%), 48 of 206 girls (23.3%), and 56 of 177 boys (31.6%) - most frequently in patients with enthesitis-related arthritis (71%), psoriatic arthritis (50%) and unclassified cases (86.7%). The age of JIA onset was slightly (by 1 year) but significantly different in patients with and without HLA-B27 antigen [11 (8.5-14) vs. 10 (5-13.5) years.; p < 0.001]. The use of disease modifying antirheumatic drugs (DMARDs) and corticosteroids was more frequently clinically ineffective in HLA-B27 positive than negative patients (23.1% vs. 15.2%; p = 0.09). Patients with polyarthritis, systemic, and psoriatic arthritis more frequently received biological therapy. HLA-B27 positive patients with enthesitis-related arthritis received biological therapy more frequently than HLA B27 negative ones (20.4% vs. 0, respectively; p = 0.09). CONCLUSIONS: HLA-B27 antigen is a strong risk factor for the development of enthesitis-related arthritis, and to a lesser extent for psoriatic arthritis and extended course of oligoarthritis. The presence of this antigen does not affect the disease onset but seems to predict resistance to therapy with disease-modifying drugs and corticosteroids. PMID- 27407239 TI - Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile. AB - OBJECTIVES: To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies. MATERIAL AND METHODS: The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays. RESULTS: The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (-0.87 +/-0.85), SOC PSMM (-0.47 +/-0.97), PAL (-1.88 +/ 3.58), and BLC (-0.31 +/-1.90). GNT scores under -0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than -0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = -0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = -0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = -0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = -0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = -0.43). The level of anti Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87). CONCLUSIONS: CANTAB reveals a decrease in selected cognitive functions in patients with SLE. ACL IgG and anti dsDNA antibodies indicated SLE patients prone to develop a decrease in cognitive functions. PMID- 27407240 TI - Pain associated with the musculoskeletal system in children from Warsaw schools. AB - OBJECTIVE: To assess the prevalence of pain in the musculoskeletal system and possible reasons for these complaints among early age children from Warsaw schools. MATERIAL AND METHODS: The study was conducted in 34 randomly selected primary schools in Warsaw in 2011. 2748 survey-questionnaires were given to parents or legal guardians by children. Of these, 1509 surveys were subject to a final analysis. The survey included 66 questions regarding, among other things, pain in the musculoskeletal system in children. Additionally, there were questions about possibly occurring diseases, any postural defects, significant obesity, as well as effects of these complaints on the child's physical activity. Survey data regarded 6-7-year-old children. RESULTS: In the group of 1509 respondents, 242 children (16%) complained about pain in the musculoskeletal system. Pain was located most frequently in the knee joints, and more rarely in the spine and joints in the upper extremities. In the group of children who complained about pain, moderate physical activity was statistically significantly limited. According to parents, physicians did not diagnose any medical conditions in 106 children. Joint disease was diagnosed in 33 children. Postural defects were diagnosed in 589 children. In 123 children complaining about pain at least one postural defect was diagnosed. Such defects were diagnosed statistically significantly more rarely (p = 0.011) in 1234 children who did not complain about pain (460 children). Platypodia or other foot deformation was observed in 25% of these children, spinal curvature in 12%, abnormal knee joint position in 11% and uneven hip position in 2% children. Of note, 17% of all children were significantly overweight. In overweight children the prevalence of pain, especially in the knee joints and feet, was significantly higher. CONCLUSIONS: This study aims to underline the problem of musculoskeletal pain in early-age children which limits their physical activity. Also the authors draw attention to the issue of postural defects in a large group of school children. This issue undoubtedly requires more attention and a plan how to create more effective methods of prevention. PMID- 27407241 TI - U1-RNP and Toll-like receptors in the pathogenesis of mixed connective tissue diseasePart II. Endosomal TLRs and their biological significance in the pathogenesis of mixed connective tissue disease. AB - Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP component engages immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. The anti-U1-RNP autoantibodies form an immune complex with self RNA, present in MCTD serum, which can act as endosomal Toll-like receptor (TLR) ligands. Inhibition of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, tumorigenesis and autoimmunity. In this review we summarize current knowledge of endogenous TLRs and discuss their biological significance in the pathogenesis of MCTD. In part I we described the structure, biological function and significance of the U1-RNP complex in MCTD. PMID- 27407242 TI - Metabolomics and its potential in diagnosis, prognosis and treatment of rheumatic diseases. AB - The main aim of metabolomics is to make a comprehensive study of metabolites, the intermediates of biochemical processes in living organisms. Any pathophysiological mechanism caused by disease will inevitably lead to related changes in the concentrations of specific metabolites. In line with this, metabolomics offers a promising laboratory tool for the analysis of potential diagnostic biomarkers that may be used to assess susceptibility to a disease and to evaluate the prognosis and therapeutic response to treatment. Recent data have shown that metabolomics analysis in rheumatoid arthritis has made possible more efficient diagnosis, discrimination between patients with regard to disease activity, prediction of the response to a particular treatment approach, differentiation between rheumatic disease subtypes and greater understanding of the pathophysiology of this disease. Here we characterize metabolomics as a comprehensive laboratory tool and review its potential in the diagnosis, prognosis and treatment of rheumatic diseases such as rheumatoid arthritis. PMID- 27407243 TI - Juvenile idiopathic arthritis complicated by amyloidosis with secondary nephrotic syndrome - effective treatment with tocilizumab. AB - A case report of a boy with juvenile idiopathic arthritis since the age of 2 years, generalized onset, complicated by nephrotic syndrome due to secondary type A amyloidosis is presented. In the patient the disease had an especially severe course, complicated by frequent infections, making routine treatment difficult. Amyloidosis was diagnosed in the 5(th) year of the disease based on a rectal biopsy. Since the disease onset the boy has been taking prednisolone and sequentially cyclosporine A, methotrexate, chlorambucil, etanercept, and cyclophosphamide. Clinical and laboratory remission was observed after treatment with tocilizumab. After 42 months of treatment with tocilizumab the boy's condition is good. There is no pain or joint edema, and no signs of nephrotic syndrome. PMID- 27407244 TI - Unusual location of tuberculosis in the course of tumor necrosis factor alpha inhibitor therapy. AB - Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex mycobacteria. Extrapulmonary tuberculosis usually develops more than two years after infection or many years later. Factors favoring onset of the disease are malnutrition, older age, renal failure, diabetes, cancer, immunosuppression and biological treatment, e.g. tumor necrosis factor alpha (TNF-alpha) inhibitors. The paper presents a case of a 56-year-old patient with ankylosing spondylitis treated with infliximab, diagnosed with tuberculosis of the spleen. The unusual location and uncharacteristic symptoms created a lot of diagnostic difficulties, particularly as during qualification for biological treatment tests are performed to exclude infection with Mycobacterium tuberculosis. Pharmacological treatment of tuberculosis is typical, but in the case of tuberculosis of the spleen, splenectomy also is a method of treatment. The decision was made to implement pharmacological treatment, which proved to be effective, so the patient avoided surgery. PMID- 27407245 TI - Position of magnetic resonance in the imaging of inflammatory rheumatic diseases. PMID- 27407246 TI - Analysis of the clinical picture in patients with osteoarthritis of the spine depending on the type and severity of lesions on magnetic resonance imaging. AB - OBJECTIVES: Spondyloarthritis is the most common pathological change in the spine. In a significant number of cases, it leads to compression of the nervous structures of the spinal canal, causing pain and neurological symptoms. Intervertebral disc pathology is a common cause of root deficits in neurological examination of all types of degenerative changes of the spine structures. Disc herniation is pathologically divided into 4 stages of herniated nucleus pulposus: 1) bulging, 2) protrusion, 3) extrusion, 4) sequestration. The aim of this study is to analyze the correlation between the type and severity of degenerative changes in the spine and the incidence of neurological deficits. MATERIAL AND METHODS: The study included 100 patients: 74 men and 26 women aged 50.2 +/-10.43 years with pain of the spine in the cervical and/or lumbosacral segments and with degenerative changes in the plain radiographs. The mean value of body mass index (BMI) was 27.8 +/-3.95 kg/m(2). Each patient underwent neurological examinations and 1.5 T magnetic resonance imaging MRI of the cervical and/or lumbar spine. RESULTS: Every patient was diagnosed with herniated nucleus pulposus affecting on average 4 +/-2 segments of the spine. The most frequently observed degree of severity of disc herniation was the second (protrusion, 71.9% of all disc disease in 89 patients). Much less frequently found was the third degree (extrusion, 45 patients, 20.1% slipped disc), the first (bulging, 14 patients, 6.3% slipped disc), and least often only a small percentage of fourth degree (sequestration, 4 patients, 1.7% slipped disc). Neurological symptoms (deficits) were observed in 34 patients. They were accompanied by disc herniations in 23.7% of patients. In remaining patients with neurological deficits there was spinal stenosis. No correlation was observed between neurological deficits and stage 1 of disc herniation. CONCLUSIONS: The incidence rate of neurological deficits is correlated with the degree of changes in the spine, as visualized by MRI. PMID- 27407247 TI - Patterns of compensation of functional deficits of the knee joint in patients with juvenile idiopathic arthritis. AB - OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a group of pathological syndromes of unknown aetiology, observed at the developmental age. Their common feature is sustained chronic arthritis with flares and remissions. Clinical signs and symptoms include joint pain, periarticular tissue oedema or articular exudate, frequently associated with hypertrophy of the synovial membrane. The intra- and extra-articular structural damage impairs the motion range and smoothness. The disease process may involve any joint. The knee joint is the most frequently affected in oligo- and polyarthritis. The aim of the study was to determine a direct correlation between disorders of knee joint function and the change in the range of motion of the ankle and hip joints of both lower extremities, and the so-called indirect impact of these changes on patients' posture. MATERIAL AND METHODS: The study included 36 JIA patients and 56 healthy controls aged 8-16 years. The evaluation was based on physical examination. RESULTS: The results showed differences in the values of quality and range of motion between patients and controls. In the patient group pes planovalgus was more frequently associated with knee joint dysfunction along with the inherent restriction of dorsal flexion of the foot. Shortening of the iliotibial band, increased outward rotation of the right lower extremity with enlarged joint contour and augmented inward rotation of the contralateral healthy extremity all proved significant. Changes in motion range in the joints below and over the knee were associated with alterations of antero-posterior spine curvatures and vertebral rotation along the long spinal axis. Based on the results, the mechanism of the compensation is outlined. CONCLUSIONS: The observed differences in the range and quality of motion in the ankle, hip and spinal joints between patients and healthy children provide evidence that dysfunction of the knee joint affects the function of the other above-mentioned levels of the motor system. PMID- 27407248 TI - Rheumatoid arthritis treatment with TNF inhibitors and alternative procedures in case of its failure - results of the Polish survey in the context of EULAR recommendations. AB - INTRODUCTION: According to the European League Against Rheumatism (EULAR), rheumatoid arthritis (RA) treatment aims to achieve remission or low disease activity (LDA) within 6 months. In Poland, despite the existence of the National Health Fund Drug Program (NHF-DP), data on the effects of treatment with biological agents in patients with RA are not publicly available. Also we cannot compare registers from other countries with the Polish results because the rules of the therapeutic program in Poland impose restrictions that do not exist in other countries. For this reason, the data will not be comparable, but the results of the currently used regimen for biological treatment in Poland should be analyzed and compared with the recommendations of the European EULAR as a contribution to further discussion. OBJECTIVES: To determine the tumor necrosis factor alpha (TNF-alpha) inhibitor treatment patterns in RA patients in Poland, to evaluate the frequency and causes of treatment failure as well as post-failure recommendations, and to compare Polish clinical practice enforced by the therapeutic program with the EULAR recommendations. MATERIAL AND METHODS: The data on 895 RA patients were retrospectively collected from routine medical records. A questionnaire was completed only once for each patient. RESULTS: After 3 months of treatment with a TNF-alpha inhibitor, the therapeutic target was achieved in 72% of patients: 4% in remission, 8% LDA, and 60% with moderate disease activity (MDA); after 9 months, 46% had reached the target: 16% in remission, 30% with LDA. An average of 49% of patients presented with MDA or high disease activity (HDA), thus requiring treatment modification. Treatment failure was confirmed in 14% of patients and a modified therapy administered: rituximab (72%) or adalimumab (20%). The most common cause of failure was inefficacy of treatment (70%). CONCLUSIONS: In the Polish therapeutic program, despite the persistence of MDA or HDA, the treatment with TNF inhibitors rarely qualifies as ineffective and therefore is seldom modified by switching to another biologic drug. As long as the initiation of treatment and its modifications are enforced by the NHF-DP and not the recommendations of EULAR, treatment may be less effective and paradoxically cost-intensive. Therefore, it seems obvious that it is necessary to change and adapt the NHF-DP requirements to European standards. PMID- 27407249 TI - Fatigue and interleukin-6 - a multi-faceted relationship. AB - Many connective tissue diseases are characterized by fatigue, which is described in the literature as prostration, weakness, lassitude or asthenia. In many other diseases (autoimmune, neurologic or metabolic) fatigue impinges on daily activities and thus influences the quality of life. Different molecular backgrounds are involved in the development of fatigue. Not only does the immunosuppressive treatment of autoimmune diseases reduce fatigue, but also selective nutritional components may have an effect on secretion of cytokines which are responsible for development of the sensation of tiredness (e.g. secretion of interleukin-6). The beneficial influence of selected food components (such as polyunsaturated omega-3 fatty acids, nutritional antioxidants or adequate fat intake with the diet) on proinflammatory cytokine secretion has been demonstrated in many studies. In this review, the biochemical, neurological and nutritional aspects of fatigue in autoimmune diseases are underlined. PMID- 27407250 TI - DAS28 score vs. ultrasound examination for assessment of rheumatoid arthritis disease activity: comparison and discussion of pros and cons. AB - Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease which is characterized by symetrical multiple joints involvement and extra-articular symptoms. Current EULAR diagnostic criteria for RA include disease activity parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which are used to calculate disease activity scores, including DAS and DAS28. Recently attempts have been made to assess disease activity using imaging diagnostic modalities, such as magnetic resonance imaging (MRI) and ultrasonography (US). Due to significant progress in therapy effectiveness and early RA diagnosis possibility, imaging modalities become increasingly meaningful and many clinical trials confirm their usefulness. However, there are no consistent criteria for objective assessment of therapy effectiveness based on US. Moreover, it is not US availability that limits its common use, but rather significant variability between operators. This is why US remains only an additional tool to assess therapy efficacy with regard to DAS/DAS28 index. PMID- 27407251 TI - The role of physiological elements in future therapies of rheumatoid arthritis. III. The role of the electromagnetic field in regulation of redox potential and life cycle of inflammatory cells. AB - Each material consisting of charged particles can be influenced by a magnetic field. Polarized particles play an essential role in almost all physiological processes. Locally generated electromagnetic fields several physiological processes within the human body, for example: stimulation of nerves, muscles, and cardiac electrical activity. This phenomenon is used today in many medical applications. In this article, we discuss ways in which electromagnetic field affects the physiological and pathological processes in cells and tissues. This knowledge will help to better understand the electrophysiological phenomenon in connective tissue diseases and can bring new therapeutic strategies (in the form of "invisible drugs") for the treatment of rheumatic diseases? PMID- 27407252 TI - Atypical course of Henoch-Schonlein purpura in an adult patient. AB - Henoch-Schonlein purpura is vasculitis of small blood vessels characterized by deposits of IgA immune complexes and also non-thrombocytopenic purpura, abdominal pain, arthritis and renal involvement. It affects people of all ages, but most cases occur in children between 2 and 11 years old, more frequently in boys. The disease is much less common in adults, who often have a more severe course of the disease. The paper presents the case of a 38-year-old female patient with insidious course of the disease, initially dominant skin symptoms and joint pain without signs of inflammation. Symptoms of the disease were initially uncharacteristic and mild, and did not suggest severe and rapid course of the disease. The patient required hospitalization in several departments before final diagnosis of Henoch-Schonlein purpura. The patient was treated with corticosteroids and immunosuppression. Despite the rapid course of the disease, treatment was effective. The patient was discharged in good condition. PMID- 27407253 TI - Inflammatory bowel disease-related arthritis - clinical evaluation and possible role of cytokines. AB - OBJECTIVES: In inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation, rheumatic abnormalities ranging from arthralgia to spondyloarthritis (SpA) are the most common extraintestinal manifestations. The pathogenesis of IBD-related arthritis is unclear. In this study, we search for clinical and immunological differences between patients with IBD-associated spondyloarthritis and IBD patients without SpA symptoms. MATERIAL AND METHODS: Patients with an established diagnosis of IBD, suffering from Lesniowski-Crohn disease (L-CD, n = 24) or ulcerative colitis (UC, n = 27), were enrolled in the study. Clinical evaluation of patients, based on medical history, blood tests, physical and radiological examinations, allowed two subgroups of patients to be established. One subgroup comprised patients fulfilling criteria for both IBD and SpA (IBD + SpA, n = 29), while the other included IBD patients with arthralgia only (IBD, n = 22). Serum concentrations of interleukins (IL-6, IL-10, IL-21, IL 22, IL-23) and interferon gamma (IFN-gamma) were measured by specific enzyme linked immunosorbent assays (ELISA). RESULTS: Patients with IBD + SpA were characterized by shorter disease duration (3 vs. 9 years), higher frequency of HLA-B27 positivity (60.7% vs. 4.5%) and uveitis (20.7% vs. 0%), compared with the IBD subgroup. The serum concentrations of C-reactive protein (CRP) and tested cytokines did not differ between IBD + SpA and IBD patients, or between L-CD and UC groups. However, in the IBD + SpA subgroup there was weak to moderate positive correlation between serum concentrations of CRP and several cytokines (IL-6, IL 21, IFN-gamma), and additional moderate positive correlation between serum concentrations of IL-23 and clinical activity of SpA. By contrast, in IBD subgroup a strong inverse correlation between serum concentrations of Interleukin 23 and CRP was found. CONCLUSIONS: IBD-related spondyloarthritis occurs relatively early, affects mostly HLA-B27(+) individuals, and is often accompanied by ocular involvement. In these patients several circulating cytokines are associated with systemic inflammation. IL-23 seems to be protective in IBD while detrimental in IBD-related spondyloarthritis. PMID- 27407254 TI - Correlation between erythrocyte sedimentation rate and C-reactive protein level in patients with rheumatic diseases. AB - OBJECTIVES: Erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) are the acute phase reactants most commonly determined in patients with rheumatic diseases. The indices are affected by different factors, but both of them are applied for evaluation of the disease activity in patients with inflammatory disorders of the musculoskeletal system. MATERIAL AND METHODS: The authors compared the results of ESR and CRP, which were carried out during routine diagnosis in 200 patients admitted to the Department of Rheumatology. RESULTS: A significant correlation between ESR and CRP was found (ESR after 1 h/CRP: correlation coefficient 0.6944, ESR after 2 h/CRP: correlation coefficient 0.6126). There was no difference in ESR or CRP between male and female patients, and patients older than 40 years had higher ESR and CRP. CONCLUSIONS: The obtained results support the usefulness of both indices in the clinical practice of rheumatologists. PMID- 27407255 TI - Assessment of the usefulness of skin autofluorescence as an indicator of disease activity and of the risk of developing diabetes in patients suffering from rheumatoid arthritis. AB - OBJECTIVES: Diabetes develops much more often in patients suffering from rheumatoid arthritis (RA) than in healthy population. One of the parameters which allow to evaluate the risk of developing diabetes and cardiovascular diseases (CVD) is the level of advanced glycation end products (AGE) in the skin. In patients suffering from RA, an increase in AGE level may be also linked with the course of the underlying disease. The aim of the study was to evaluate the correlation between the AGE level and the course of RA as well as other risk factors for the development of diabetes and CVD. MATERIAL AND METHODS: The study included 148 patients divided into three groups: group I - patients with RA (n = 102, 79 F/23 M), group II - patients with RA and diabetes (n = 21, 14 F/7 M), group III - healthy individuals (n = 25, 16 F/9 M). Each patient underwent a skin autofluorescence signal (SAF) examination with an AGE Reader, which allows the assessment of AGE level, as well as being subjected to the laboratory tests panel. Additionally, patients from group I and II have had their DAS28 (ESR) indicator calculated. RESULTS: In groups I, II, and III, the respective mean SAF values, expressed in arbitrary units [au], were to 2.54, 2.74, and 1.96 au. Between-group differences in terms of mean SAF values were statistically significant (p < 0.05). CONCLUSIONS: Significantly higher mean SAF values in groups I and II as compared to group III suggest that the increase in the AGE level in patients with RA is linked with the underlying disease and does not have to correspond with the real risk of diabetes and CVD. In conclusion, despite the known limitations of the technique, measuring AGE levels allows for closer monitoring of RA patients who are at a higher risk of developing diabetes. PMID- 27407256 TI - Supply and demand for long-term care services from the perspective of leaders of health care institutions. AB - INTRODUCTION: Poland's transition into the stage of intensive population aging imposes changes in demand for different forms of care (including long-term). The proportion of dependent persons (requiring care) in the population continues to increase. The number of people aged 80 and above (in 2013 - 1.48 million) will double by 2050 and reach 3.54 million. The research objective was to gain knowledge on the supply and demand of different institutionalized forms of care services from the healthcare system perspective. MATERIAL AND METHODS: A computer assisted personal interview (CAPI) survey was carried out on a Poland-wide quota sample of health care and nursing centres operating within the healthcare system. The respondent group consisted of 96 directors of health care facilities. RESULTS: In the opinion of more than a half of surveyed directors, supply of health care and nursing centres in their region is insufficient in terms of the needs of both patients and elderly people. In the context of patients, the deficit is observed primarily in health care and treatment centres, long-term nursing care and health care institutions, whereas for the elderly people the main concern is availability of nursing care, day care or social aid centres. More than half of surveyed institutions admit patients requiring care on an ongoing basis; however, in the case of health care and treatment centres more than a year-long waiting time proved to be a frequent phenomenon. In the opinion of the surveyed directors, the key factors influencing the number of available places and waiting time are insufficient financing and personnel deficit. CONCLUSIONS: Introduction of multiple changes to the operation of the care system in Poland is necessary in order to improve its availability, effectiveness and quality. Achievement of this objective requires implementation of a cohesive and integrated system dedicated to monitoring and diagnosing both the supply and demand for different forms of care. PMID- 27407257 TI - Analysis of information on rheumatology from a selected Internet forum in the context of the need for telemedicine solutions. AB - OBJECTIVES: The aim of this study was to determine how often patients and undiagnosed people who complain of musculoskeletal system and rheumatic diseases look for knowledge contained on an Internet forum. Content analysis was used to identify the level of Internet users' activity in the rheumatology section, compared to other areas of medicine. MATERIAL AND METHODS: Material included information posted on the Internet forum established at http://medyczka.pl/. The method employed was a quantitative and qualitative analysis of the content. The method was based on qualitative assessment of the first post in each thread presented on the rheumatologic subforum, by assigning keywords, subjectively determined by the researcher, to such a post. For each keyword a specific definition was established, determining a situation in which a given keyword was used. RESULTS: The quantitative analysis qualified rheumatology in the last place in terms of Internet users' activity compared to other branches of medicine. The qualitative assessment of the rheumatologic forum indicated that the three most common keywords were joint pain (32), joints swelling (13), and schoolage (13). The three most common intentional keywords (arranged in order of their decreasing number) were diagnosis based on symptoms (29), interpretation of the laboratory test results (9), and how to deal with symptoms (8). CONCLUSIONS: The analysis leads to the conclusion that the rheumatologic subforum, along with other subforums listed above, presents a critically low level of discussion. There is a large disproportion between the number of active and passive forum users, suggesting that numerous individuals search the forum for presented information. Based on the qualitative analysis of the information stocks of the rheumatologic subforum, it was established that most of the questions posted concerned young individuals, who complained of joint pain and swelling, and asked for a possible diagnosis based on the presented symptomatology, interpretation of the laboratory test results and alleviation of disease symptoms. PMID- 27407258 TI - Indirect costs of rheumatoid arthritis. AB - It is estimated that in Poland about 400,000 persons in general suffer from inflammatory joint diseases, including rheumatoid arthritis (RA). Epidemiological surveys documenting the frequency and disturbance of musculoskeletal disorders in the Polish population are few in number. Most of the estimations are based on epidemiological data from other countries (prevalence of 0.5-1%). According to the data of the National Health Fund in Poland 135,000-157,000 persons in total are treated because of rheumatoid arthritis per year [ICD10 (International Statistical Classification of Diseases and Related Health Problems): M05, M06]. In the case of this group of diseases indirect costs significantly outweigh the direct costs. Indirect costs increase together with activity level of the disease. The cost analysis of productivity loss of RA patients indicates that sickness absenteeism and informal care are the most burdensome. At the national level it amounts in total from 1.2 billion to 2.8 billion PLN per year, depending on the method of analysis. These costs could be significantly reduced through early diagnosis and introduction of effective treatment. PMID- 27407259 TI - Multiple pulmonary rheumatoid nodules. AB - We present a case of 45-year-old female patient with the diagnosis of seropositive rheumatoid arthritis, who was admitted to our rheumatology department with exacerbation of the disease. The patient's disease activity score (DAS 28) was 6.9. Physical examination revealed changes in the lung auscultation as a rough breathing sound at the middle and lower lobe of the right lung. Chest X-ray revealed multiple nodular densities in both lungs. Lung biopsy was performed for the diagnosis and revealed necrotizing granulomas with central fibrinoid necrosis surrounded by epithelioid cells. Such a histopathological picture is typical for rheumatoid nodules. Finally the patient was treated with rituximab, with significant improvement. PMID- 27407260 TI - Coexistence of rheumatoid arthritis and ankylosing spondylitis. AB - Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic progressive inflammatory diseases, leading to joint damage and reducing the physical fitness of patients. They are among the most common rheumatic diseases. However, their etiology and symptomatology are different. Formerly, AS was often wrongly diagnosed as RA. Today there are no major diagnostic difficulties in differentiation between these diseases, thanks to modern laboratory tests and imaging. However, a problem may arise when the patient has symptoms typical for both diseases simultaneously. Cases of coexistence of RA with AS - according to our best knowledge - are rare. This study aims to compare our experience in diagnosis and treatment of concomitant RA and AS with the experience of other researchers. Implementation of the proper diagnostic algorithm, allowing for correct diagnosis of both diseases in one patient, may be useful for differential diagnosis of similar cases in the future. PMID- 27407261 TI - Infectious complication or exacerbation of granulomatosis with polyangiitis? AB - Granulomatosis with polyangiitis (GPA) is a primary, systemic small vessel vasculitis. The respiratory tract is typically involved in the course of the disease. Abnormalities on the chest radiograph are noted in more than 70% patients at some point during their disease history. In some clinical situations it is difficult to distinguish whether symptoms result from the underlying disease or are a symptom of infection. In these clinical situations, chest computed tomography (CT) can be very useful. We present a patient with GPA localized mainly in the respiratory tract with sudden deterioration of the general state and new abnormalities revealed in the CT of the chest. PMID- 27407262 TI - Disease activity, quality of life and indirect costs of reduced productivity at work, generated by Polish patients with ankylosing spondylitis. AB - OBJECTIVES: The aim of the study was to investigate the association between activity of ankylosing spondylitis (AS) and decrease in quality of life as well as productivity loss of affected patients in a specified group of patients in the Polish setting. MATERIAL AND METHODS: An questionnaire survey was conducted using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) to assess disease activity, as well as the Work Productivity and Activity Impairment Questionnaires to assess productivity loss; quality of life was presented as utility calculated using the EuroQol 5 questionnaire and also measured on a visual analogue scale (VAS). Indirect costs were assessed with the human capital approach implying gross domestic product per capita or gross value added per worker in Poland in 2014 and were expressed in Polish zlotys (PLN) as well as in euros. Correlation was presented using Spearman's rank correlation coefficient. RESULTS: We performed our analysis based on 78 full questionnaires collected. A mean BASDAI score of 5.91 in the analysed group of patients was detected and mean utility of 0.5135 was observed. Average quality of life measured on the visual analogue scale was 46.55. Mean number of days off work was 45.26 days per year and mean on the-job productivity loss was 49.29%. Average annual indirect costs per patient were ?4241 (17 686 PLN) calculated using gross domestic product and ?10 172 (42 417 PLN) estimated using gross value added. Total productivity loss was significantly correlated with disease activity (strong correlation of 0.6005) and utility (moderate correlation of -0.3698). CONCLUSIONS: Ankylosing spondylitis causes a great decrease in quality of life as well as patients' productivity loss associated with both absenteeism and presenteeism. The greater the disease activity is, the lower is the utility, the lower is the quality of life measured on the VAS, and the greater are the total annual indirect costs. Total indirect costs were negatively correlated with utility; although the association was moderate, it was significant. PMID- 27407263 TI - Milk fat globule E-8 and interleukin 17 in systemic lupus erythematosus: partners in crime? AB - OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-factorial, autoimmune disease with a wide array of manifestations. The pro-inflammatory cytokine interleukin (IL)-17 has been implicated in the inflammatory response and tissue damage in SLE; however, its correlation with disease activity is still questionable. Meanwhile, efficient clearance of apoptotic cells is required for immune tolerance. An abnormally low or high level of milk fat globule (MFG-E8) can result in impaired apoptotic cell clearance and the subsequent autoimmune response. In this study, we endeavoured to compare the levels of MFG-E8 and IL-17 in SLE patients and healthy controls and to reveal the alleged association of these levels with SLE disease activity. MATERIAL AND METHODS: Serum samples from 57 SLE patients and 30 healthy control subjects were examined for quantitation of MFG-E8 and IL-17 levels using ELISA. Systemic lupus erythematosus disease activity was calculated using the SLE Disease Activity Index (SLEDAI). Clinical manifestations and laboratory findings of the patients were also recorded. RESULTS: We report that serum MFG-E8 levels were significantly elevated in the sera of SLE patients compared to healthy controls (p-value = 0.019). Likewise, IL 17 levels were higher in SLE patients (p-value < 0.001). A positive correlation was revealed between MFG-E8 level and proteinuria. Surprisingly, there was a poor correlation between disease activity and the levels of either IL-17 or MFG-E8. CONCLUSIONS: Although serum MFG-E8 and IL-17 levels were higher in SLE patients than in normal controls, our results indicate that they cannot accurately reflect the disease activity. Meanwhile, further studies are needed to assess MFG-E8 and IL-17 as potential therapeutic targets in SLE patients. PMID- 27407264 TI - Comparison of clinical and serological parameters in female and male patients with systemic sclerosis. AB - OBJECTIVES: The course of systemic sclerosis (SSc) can differ in female and male patients. According to the literature the incidence rates of diffuse cutaneous SSc, scleroderma renal crisis and digital ulceration are higher in male patients. The aim of the study was to compare selected clinical and serological parameters in male and female patients with SSc. MATERIAL AND METHODS: The study encompassed 101 European Caucasian patients with SSc, including 23 men, hospitalized in the Department of Rheumatology. Patients fulfilled the American Rheumatism Association (ARA) classification criteria for SSc. The study groups of men and women were assessed according to the SSc subtype, incidence of internal organ involvement and presence of antinuclear antibodies considered SSc markers. RESULTS: Diffuse cutaneous (dc) SSc was observed more commonly in men than in women (13/23 vs. 25/78; p = 0.03). The time from the development of Raynaud's phenomenon to the diagnosis was significantly shorter in male compared to female patients (3.2 +/-4.7 vs. 7.5 +/-7.1; p = 0.01). The incidence of scleroderma renal crisis (SRC) was significantly higher (3/23 vs. 2/78; p = 0.04) and of other calcifications significantly lower in the male group compared to the female group (1/23 vs. 20/78; p = 0.02). CONCLUSIONS: We concluded that the incidence of dcSSc is higher in men compared to women. The time from the development of Raynaud's phenomenon to the diagnosis is shorter in the male compare to female group. The incidence of SRC is higher, whereas that of calcifications is lower in SSc men. The serological profiles of female and male patients with SSc are comparable. PMID- 27407265 TI - The relationship between the presence of autoantibodies, indicators of local and systemic inflammation, the serum concentration of B-cell activating factor (BAFF) and the intensity of salivary gland infiltration in patients with primary Sjogren's syndrome - a preliminary study. AB - OBJECTIVES: The aim of this study was to find markers related to activation of B cells, which show a correlation with the systemic inflammation markers - erythrocyte sedimentation rate and C-reactive protein and with the intensity of in situ inflammation. MATERIAL AND METHODS: Forty-one primary Sjogren's syndrome (pSS) patients (33 female, 8 male) of the mean age 52.9 +/-15 years were included. A group of 20 healthy volunteers was applied as a control. Erythrocyte sedimentation rate (ESR), concentration of gamma-globulins, C-reactive protein (CRP) and rheumatoid factor (RF) were measured by routine laboratory tests. Titres of antinuclear antibodies (ANAs) were determined by the indirect immunofluorescence method, while anti-SS-A/SS-B antibodies were detected by both the dot-blot method and an enzyme immunoassay. The concentrations of BAFF in sera were measured by sandwich ELISA. Biopsies of minor salivary glands were taken and the focus score (FS) was calculated. Correlations between quantitative variables were assessed using the Spearman correlation coefficient (r). RESULTS: Serum concentrations of BAFF was significantly higher in the pSS patients than in the control group. The study revealed a statistically significant correlation between ANAs titre and the FS (r = 0.421). Anti-SS-A/Ro and anti-SS-B/La antibodies positively correlated with ESR. There was also a positive correlation between the gamma globulin level and the titres of all tested autoantibodies. CONCLUSIONS: The positive correlation between ANAs and FS confirms the importance of these autoantibodies in the local inflammatory process. The positive correlation between anti-SS-A/SS-B antibodies and ESR suggests involvement of these antibodies in generalization of the inflammatory response. In the pSS group serum concentrations of BAFF were statistically significantly higher than healthy volunteers. All presented results confirm the role of activity of B cells in the course of pSS. PMID- 27407266 TI - Syndromes with chronic non-bacterial osteomyelitis in the spine. AB - Chronic non-bacterial osteomyelitis (CNO) has been known for over of 40 years. It is an underrecognized entity due to the low number of described cases and poor propagation awareness of the problem. Chronic non-bacterial osteomyelitis is usually confused with infectious spondylodiscitis or malignant lesions, both primary and metastatic. Failing to consider CNO as one of possible lesions of the spine among an array of differential diagnoses may lead to a prolonged ineffective treatment increasing treatment-related morbidity. In this paper the authors describe these two syndromes, with a possible autoimmune background - chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO syndrome - that include CNO being among the manifestations. The authors present the spinal symptomatology of CNO for both syndromes published so far to help spine clinicians organize the information for better usage in everyday clinical practice. PMID- 27407268 TI - The many faces of psoriatic arthritis - a challenge to treatment to target? PMID- 27407267 TI - Interleukin 6 blockage-induced neutropenia in a patient with rheumatoid arthritis and resolved hepatitis B. AB - The authors present a case report of a 59-year-old woman with rheumatoid arthritis after documented recovery from hepatitis C (HCV) infection and with resolved HBV infection who has been undergoing successful tocilizumab treatment. The patient experienced moderate to severe neutropenia after consecutive tocilizumab administrations. However, no serious infections or HBV reactivation was recorded during that period. PMID- 27407269 TI - Efficacy of radiation synovectomy (radiosynovectomy or radiosynoviorthesis) with yttrium-90 in exudative inflammation of synovial membrane of knee joints in patients with rheumatic diseases - preliminary report. AB - OBJECTIVES: Hypertrophic and exudative synovitis of the knee is one of the earliest symptoms in rheumatic diseases. In the case of pharmacotherapy failure, other methods which directly remove the inflamed synovial membrane are used - synovectomies. Radiosynovectomy (RSV) is the radiopharmaceutical application of colloidal solution to joint cavities. In this study, the authors assessed the efficacy of knee radiosynovectomy with yttrium-90 (Y-90) in several groups of patients divided into certain rheumatic diseases. MATERIAL AND METHODS: The study group consisted of 70 patients aged from 29 to 65 years with hypertrophic and exudative synovitis of the knee in rheumatic diseases such as rheumatoid arthritis, osteoarthrosis and spondyloarthropathies. Radiopharmaceutical colloid of Y-90, with a radiation dose of 185-222 MBq in a volume of 2-3 ml, was administered to joint. Then the knee joint was immobilized for 72 h. During visits V1, V2, V3 and V4, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured and ultrasound of the knee was performed. Disease activity was evaluated by the WOMAC scale, HAQ and 100-mm visual analog scale (VAS). RESULTS: The most significant difference of synovial hypertrophy, before and after the procedure, was obtained in patients with rheumatoid arthritis. Variability of effusion before and after the procedure in all groups was comparable and statistically significant. The greatest improvement in variability of inflammatory parameters, before and 4 weeks after radiosynovectomy, was observed in patients with rheumatoid arthritis. CONCLUSIONS: In the therapeutic algorithm radiosynovectomy should be located between conservative treatment and operative procedures. Radiosynovectomy does not require hospitalization or prolonged rehabilitation. Radiosynoviorthesis affects the patient's general condition, which is associated with eliminating pain and restoring joint function. PMID- 27407270 TI - Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women - a pilot study. AB - OBJECTIVES: Osteoprotegerin (OPG) has an important role in bone remodeling, and it has been proposed that the OPG gene might be a candidate gene for osteoporosis predisposition. Several studies have already assessed the connection between OPG gene polymorphism and bone mineral density (BMD). In this study we wanted to analyze the association of two polymorphisms in the OPG gene with BMD and bone turnover markers in women with and without osteoporosis. MATERIAL AND METHODS: In 22 postmenopausal women with osteoporosis (aged 65.6 +/-12.6) and 59 women without osteoporosis (aged 60.8 +/-8.7) we analyzed the association of two polymorphisms in the OPG gene with BMD, measured by dual energy absorptiometry and with bone turnover markers (crosslaps and osteoprotegerin). A163G, G209A, T245G and G1181C polymorphisms were determined. RESULTS: No significant differences in age, anthropometry, number of fractures, osteocalcin and cross laps were found between women with and without osteoporosis. Women with osteoporosis were significantly longer in postmenopause. Significantly more women with osteoporosis had AG polymorphism (p = 0.038) compared to women without osteoporosis, while no significant difference was found in prevalence of TT and GG polymorphism between patients with and without osteoporosis. No relationship was found between investigated polymorphism and bone turnover markers. A significant negative correlation between total hip BMD and crosslaps (p = 0.046) as well as between total hip T score and crosslaps (p = 0.044) was found in women without osteoporosis. CONCLUSIONS: Postmenopausal women with osteoporosis had AG polymorphism more frequently than women without osteoporosis. Our results indicate that A163G polymorphism could have an impact on higher bone loss in postmenopausal women. PMID- 27407272 TI - Methotrexate efficacy and tolerability after switching from oral to subcutaneous route of administration in juvenile idiopathic arthritis. AB - OBJECTIVES: Methotrexate (MTX) is one of the most frequently used, highly effective disease-modifying drugs in juvenile idiopathic arthritis (JIA) therapy. The drug can be administered orally or subcutaneously, but the efficacy and tolerance of these two routes of administration raise doubts in JIA patients. The aim of the study was to evaluate MTX efficacy and tolerability after switching from the oral to the subcutaneous route of administration in children with JIA. MATERIAL AND METHODS: A single-centre, questionnaire-based assessment of MTX efficacy and tolerance in 126 unselected JIA patients with longer than 6 months of follow-up was performed. In all patients, MTX was initially administered orally. The response to MTX treatment was analysed according to American College of Rheumatology (ACR) paediatric criteria. RESULTS: Six-month MTX therapy was effective (ACR score >= 30) in 83 children (65.9%). The oral route of MTX administration was changed to subcutaneous in 32 patients after a mean period of 14 months due to intolerance (n = 20) or reluctance to take the oral formulation (n = 12). This group of children was significantly younger (p = 0.02) but did not differ from the group of children that continued oral treatment in other aspects, including MTX dose. Six months after switching from oral to subcutaneous MTX the ACR score remained unchanged. Three children (9.4%) still reported symptoms of drug intolerance. CONCLUSIONS: The switch from oral to subcutaneous MTX may increase the response rate in JIA patients with intolerance of its oral formulation. The reluctance to take oral MTX can be anticipated in early childhood, and should be considered in the individualization of therapy, having also in mind the lower risk of severe gastrointestinal adverse drug reactions. PMID- 27407271 TI - Clinical characteristics of patients with anti-TIF1-gamma antibodies. AB - OBJECTIVES: Inflammatory myopathies are a group of idiopathic, heterogeneous systemic diseases affecting predominantly skeletal muscles, though they can also involve the skin and internal organs. The association between cancer and idiopathic inflammatory myopathies, particularly dermatomyositis, which is termed cancer-associated myositis (CAM), has been reported in the medical literature. A newly described autoantibody to a 155-kDa nuclear protein, identified as transcription intermediary factor 1-gamma (TIF1-gamma), has proven useful for cancer screening in patients with dermatomyositis. MATERIAL AND METHODS: Based on our database of laboratory results, between November 2014 and January 2016, we found 80 patients with a positive autoimmune inflammatory myopathy immunoblot profile. RESULTS: Eleven of 80 patients revealed the presence of anti-TIF1-gamma antibodies: 8 women and 3 men with average age 54.2 years. Dermatomyositis (DM) was diagnosed in 6 cases, polymyositis in 1 case, myositis limited to ocular muscles and rhabdomyolysis in 1 case each, and undifferentiated connective tissue disease in 2 cases. Neoplasm was found in 4 cases. All of those patients had DM. The average time between DM and diagnosis of neoplasm was 7.5 months (from 1 to 18 months). CONCLUSIONS: The association between cancer and idiopathic inflammatory myopathies, particularly DM, is well known, and cancer screening should be obligatory in such patients. So far there is no consensus as to the method or frequency with which patients with an idiopathic inflammatory myopathy should be tested to rule out neoplasm. Detection of anti-TIF1-gamma antibodies in patients with DM gives the clinicians the very important suggestion of CAM. It seems reasonable that these patients should have more detailed and often repeated differential diagnostics. PMID- 27407273 TI - Intestinal microbiota transplant - current state of knowledge. AB - Faecal microbiota transplantation (FMT) has induced a lot scientific interest and hopes for the last couple of years. FMT has been approved as a treatment of recurrent Clostridium difficile colitis. Highly sophisticated molecular DNA identification methods have been used to assess the healthy human microbiome as well as its disturbances in several diseases. The metabolic and immunologic functions of the microbiome have become more clear and understandable. A lot of pathological changes, such as production of short-chain fatty acids or components of the inflammatory cascade, caused by changes in microbiome diversity, variability and richness have been observed among patients suffering from inflammatory bowel diseases, irritable bowel syndrome, type 2 diabetes or rheumatoid arthritis. The published clinical results are encouraging, but still there is huge demand for FMT controlled clinical trials. PMID- 27407274 TI - Osteoporosis diagnostics in patients with rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease. The development of comorbidities often occurs in the course of RA. One of them is osteoporosis, which has serious social and economic effects and may contribute to the increase in the degree of disability and premature death of the patient. Due to the young age in which RA disease occurs, densitometry (DXA) of the lumbar spine is the basic examination in osteoporosis diagnostics. In the course of RA, much more frequently than in healthy persons of the same age, osteoporotic fractures of vertebral bodies occur, which hinder a correct assessment in the DXA test. Rheumatoid arthritis patients often undergo computed tomography (CT) examination of the abdominal cavity for other medical indications than suspected spinal injury. Then, CT examination may also serve for the assessment of bone density, especially in patients with osteoporotic fractures. PMID- 27407275 TI - Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease. AB - Rituximab (RTX) is a monoclonal chimeric antibody directed against the CD20 antigen of B lymphocytes. Late onset neutropenia (LON) is a recognised complication of rituximab usually occurring 4 weeks after the last dose and is reported in both haematological and rheumatological conditions. However, it has never been described in a patient with myositis and systemic sclerosis overlap disease. We describe a case of LON in a 54-year-old man who was diagnosed with myositis and then systemic sclerosis overlap disease. It resolved within 7 days, and the patient did not suffer neutropenic sepsis or any other complications. We propose similar mechanisms for LON as described in other conditions and routine blood monitoring in such patients. PMID- 27407276 TI - Eosinophilic fasciitis after parasite infection. AB - Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non parasitic infections or cancer. PMID- 27407277 TI - Macrophage activation syndrome in a patient with systemic onset of the juvenile idiopathic arthritis. AB - Systemic onset juvenile idiopathic arthritis (sJIA) is defined as arthritis affecting one or more joint usually in the juvenile age group (< 16 years of age) with or preceded by fever of at least 2 weeks duration that is documented to be daily ("quotidian") for at least 3 days which may be associated with evanescent (non-fixed) erythematous rash or generalized lymph node enlargement or hepatomegaly/splenomegaly/both or serositis. Macrophage activation syndrome (MAS) is a life-threatening complication of sJIA marked by sudden onset of non remitting high fever, profound depression in all three blood cell lines (i.e. leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. We report a case of a 16-year-old female patient presenting with high grade fever with joint pains and generalized weakness which proved to be systemic onset juvenile idiopathic arthritis with macrophage activation syndrome after ruling out all other differential diagnoses and responded well to intravenous steroids. PMID- 27407278 TI - Repeat renal biopsy in lupus nephritis - unnecessary harm and risk of complications or important diagnostic tool with clinical consequences? PMID- 27407279 TI - Different expression of chemokines in rheumatoid arthritis and osteoarthritis bone marrow. AB - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. In addition to involvement of the joints, there is growing evidence that inflammatory/autoimmune processes take place in bone marrow, beginning the disease onset. Activated T and B cells accumulate in bone marrow, where also effective antigen presentation takes place. An increased number of activated T cells was observed in RA in comparison to osteoarthritis (OA) bone marrow. In the present study we analyzed the levels of chemokines that may be responsible for accumulation/retention of T-cells in the bone marrow of RA and OA patients. MATERIAL AND METHODS: Bone marrow samples were obtained from RA and OA patients during total hip replacement surgery, and bone marrow plasma was obtained by gradient centrifugation. Levels of the chemokines CX3CL1, CCL5, CCL2, CXCL12 and CXCL1 were measured in bone marrow plasma by specific ELISAs. Comparison between the groups of patients and statistical significance were analyzed by the two-tailed Mann-Whitney U test. RESULTS: Increased levels of CX3CL1 (818 +/-431 pg/ml vs. 502 +/-131 pg/ml, p < 0.0007) and CCL5 (5967 +/-1680 pg/ml vs. 4878 +/-2360 pg/ml, p < 0.05) respectively in bone marrow plasma from RA in comparison with OA patients were observed. In contrast, similar levels of CCL2, CXCL12 and CXCL1 in RA and OA bone marrow suggest that these cytokines do not play a significant role in the observed T cell accumulation in RA bone marrow. CONCLUSIONS: CX3CL1 and CCL5 overproduced in RA bone marrow may contribute to the accumulation of T cells observed in RA bone marrow. PMID- 27407280 TI - Differences in selected medical care parameters in rheumatic disease ward patients of different ages of life. AB - INTRODUCTION: Rheumatic diseases are becoming more and more common in Poland with the ageing of the population. Nearly 18% of the total hospital admissions in Poland result from rheumatic diseases, which was equivalent to 350 thousand cases in the year 2008. These diseases tend to last for many decades, decreasing both the quality of life and income of the patients as well as increasing the medical institutions' workload and society's financial burden. The aim of the study was to determine whether the medical care parameters in a rheumatic disease hospital ward show any significant differences among different patient age groups - especially such that would support taking them into account as a basis for adjusting the financial coverage level of medical services. MATERIAL AND METHODS: Data on hospitalizations at the Rheumatic Diseases Ward of Wroclaw University Hospital in Wroclaw in the years 2009-2015 were analyzed, taking into account the age groups, number of hospital admissions, their duration and causes. Relevant statistical data analysis was performed. DISCUSSION: The study revealed that the number of old patients hospitalized at the rheumatic diseases ward increased over the last 6 years and that such statistically significant differences do exist: on average the old patients not only tend to stay much longer at the hospital, but also suffer from a different and more diverse spectrum of diseases in comparison to their younger counterparts. CONCLUSIONS: The detected differences in medical care parameters support the need for more individualized medical care and increased cost of the hospital stay in the case of older patients. Consequently, those factors justify the necessity to increase the value of medical services in the case of old patients, possibly also taking into account the variation between age subgroups. PMID- 27407281 TI - Do we still need renal biopsy in lupus nephritis? AB - The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment. PMID- 27407282 TI - Capillaroscopy - a role in modern rheumatology. AB - Capillaroscopy is a non-invasive, easy and safe diagnostic technique designed to evaluate small vessels of the microcirculation in the nailfold. It can reveal both the general architecture of capillary rows and fine details of particular vessels. The most important indications for performing capillaroscopy include differential diagnosis of primary and secondary Raynaud's phenomenon, as well as assessment of scleroderma spectrum disorders. In systemic sclerosis capillary abnormalities appear and evolve in a clearly defined sequence called the scleroderma pattern, which correlates with internal organ involvement. Capillaroscopy is also listed as a systemic sclerosis classification criterion recognized by the European League Against Rheumatism (EULAR). With digitized equipment, capillaroscopy allows for precise qualitative and quantitative evaluation of the microcirculation and is a valuable tool in the rheumatologists' daily practice. PMID- 27407283 TI - Social implications of rheumatic diseases. AB - Social consequences of a disease constitute limitations in performing roles relating to working life as well as family and social life caused by the disease, mainly chronic. The aim of the study was to analyze the social consequences of rheumatic diseases in the aspect of disability pensions with respect to incapacity for work and quality of life. The occurrence of rheumatic diseases is related not only to increased risk of different types of organic changes, but above all disability. In Europe almost 50% of persons suffering from diseases of the musculoskeletal system who are currently unemployed were breadwinners. Nearly 60% of them received legal disability status. The loss of work ability is, among other things, the consequence of progressive disability. In Europe 40% of persons suffering from rheumatoid arthritis (RA) had to stop working due to the disease. Most of the persons diagnosed with RA were of working age. It results in the decrease in the quality of life as well as economic difficulties (decreased incomes and increased disease-related costs). In Poland the results of the analysis of the Social Insurance Institution (ZUS) of first-time disability recognition issued for the purpose of disability pensions in 2014 showed that the incapacity for work was caused by diseases relating to general health condition (65.5%). Diseases of the musculoskeletal system were the cause of partial inability to work of 21.6% of persons who received a disability pension for the first time (as many as 5,349 certificates were issued). Early diagnosis and implementation of effective treatment are the necessary conditions for a patient to sustain activity, both professional and social, which is of crucial importance to reduce the negative effects of the disease. PMID- 27407284 TI - Erythema nodosum - review of the literature. AB - Erythema nodosum is the most common form of panniculitis. It may have many aetiological factors. Erythema nodosum occurs three to five times more often in female patients. It appears as erythematous painful rounded nodules, located most often on the anterior surface of the lower extremities, and may be accompanied by systemic symptoms such as fever, malaise and arthralgia. During diagnosis, oncological vigilance should be maintained, because erythema nodosum may be a paraneoplastic symptom. It requires an interdisciplinary approach and exclusion of many underlying causes. PMID- 27407285 TI - Erythema nodosum - presentation of three cases. AB - Erythema nodosum (EN) is a well-known form of panniculitis. It may occur as an idiopathic form and also can be induced by certain clinical conditions such as infections and granulomatous diseases such as sarcoidosis. Erythema nodosum may be accompanied by general symptoms such as fever, weakness, and severe pain, but skin lesions resolve without skin damage. Erythema nodosum occurrence is for the clinician a signal for a wider diagnosis and determination of the cause of occurrence of symptoms. The article presents three cases of EN with different causes and treatment. PMID- 27407286 TI - Coexistence of granulomatosis with polyangiitis (GPA) and Crohn's disease or multiorgan manifestation of the same disease? AB - Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis of unknown aetiology, often related to the antineutrophil cytoplasmic antibody (ANCA). GPA was previously named Wegener's granulomatosis (WG). The disease frequently has multisystemic presentation, targeting mainly the respiratory tract and kidneys, but gastrointestinal involvement is uncommon. Crohn's disease (CD) is an inflammatory bowel disease (IBD) with many extraintestinal manifestations. Clinically, symptoms of WG and CD can mimic each other. In this paper a case of GPA manifested initially by severe multiorgan damage including colitis, regarded to be coexistent CD, is presented. The case illustrates the difficulties in establishing the diagnosis when symptoms of the diseases mimic each other. PMID- 27407287 TI - Scleroderma of geriatric age and scleroderma-like paraneoplastic syndrome - description of two cases. AB - Systemic sclerosis (Ssc) is an autoimmune connective tissue disease of unknown origin, characterized by progressive fibrosis of the skin and internal organs. Immune reactions taking part in Ssc pathogenesis may contribute to cancer development; therefore patients with risk factors for this disease require observation for a neoplastic process. On the other hand, symptoms of Ssc may be a mask of various cancers. Differentiating between the idiopathic form of Ssc and scleroderma-like paraneoplastic syndrome often causes a lot of difficulties. The article presents two cases of Ssc at the beginning of the disease after 60 years of age. The first case was diagnosed as Ssc, whereas in the second case the defined diagnosis was scleroderma-like syndrome in the course of colorectal cancer. This paper presents an analysis of differential diagnostic procedures which were performed and led to the final diagnosis, mentions types of cancers co occurring with Ssc and suggests a screening scheme for cancer development in patients with a diagnosis of Ssc. PMID- 27407288 TI - Genetics and Genomics of the Genus Amycolatopsis. AB - Actinobacteria are gram-positive filamentous bacteria which contains some of the most deadly human pathogens (Mycobacterium tuberculosis, M. leprae, Corynebacterium diphtheriae, Nocardia farcinica), plant pathogens (Streptomyces scabies, Leifsonia xyli) along with organisms that produces antibiotic (Streptomycetes, Amycolatopsis, Salinospora). Interestingly, these bacteria are equipped with an extraordinary capability of producing antibiotics and other metabolites which have medicinal properties. With the advent of inexpensive genome sequencing techniques and their clinical importance, many genomes of Actinobacteria have been successfully sequenced. These days, with the constant increasing number of drug-resistant bacteria, the urgent need for discovering new antibiotics has emerged as a major scientific challenge. And, unfortunately the traditional method of screening bacterial strains for the production of antibiotics has decreased leading to a paradigm shift in the planning and execution of discovery of novel biosynthetic gene clusters via genome mining process. The entire focus has shifted to the evaluation of genetic capacity of organisms for metabolite production and activation of cryptic gene clusters. This has been made possible only due to the availability of genome sequencing and has been augmented by genomic studies and new biotechnological approaches. Through this article, we present the analysis of the genomes of species belonging to the genus Amycolatopsis, sequenced till date with a focus on completely sequenced genomes and their application for further studies. PMID- 27407290 TI - Comparative Genomics Reveals Biomarkers to Identify Lactobacillus Species. AB - Bacteria possessing multiple copies of 16S rRNA (rrs) gene demonstrate high intragenomic heterogeneity. It hinders clear distinction at species level and even leads to overestimation of the bacterial diversity. Fifty completely sequenced genomes belonging to 19 species of Lactobacillus species were found to possess 4-9 copies of rrs each. Multiple sequence alignment of 268 rrs genes from all the 19 species could be classified into 20 groups. Lactobacillus sanfranciscensis TMW 1.1304 was the only species where all the 7 copies of rrs were exactly similar and thus formed a distinct group. In order to circumvent the problem of high heterogeneity arising due to multiple copies of rrs, 19 additional genes (732-3645 nucleotides in size) common to Lactobacillus genomes, were selected and digested with 10 Type II restriction endonucleases (RE), under in silico conditions. The following unique gene-RE combinations: recA (1098 nts) HpyCH4 V, CviAII, BfuCI and RsaI were found to be useful in identifying 29 strains representing 17 species. Digestion patterns of genes-ruvB (1020 nts), dnaA (1368 nts), purA (1290 nts), dnaJ (1140 nts), and gyrB (1944 nts) in combination with REs-AluI, BfuCI, CviAI, Taq1, and Tru9I allowed clear identification of an additional 14 strains belonging to 8 species. Digestion pattern of genes recA, ruvB, dnaA, purA, dnaJ and gyrB can be used as biomarkers for identifying different species of Lactobacillus. PMID- 27407289 TI - Diverse Metabolic Capacities of Fungi for Bioremediation. AB - Bioremediation refers to cost-effective and environment-friendly method for converting the toxic, recalcitrant pollutants into environmentally benign products through the action of various biological treatments. Fungi play a major role in bioremediation owing to their robust morphology and diverse metabolic capacity. The review focuses on different fungal groups from a variety of habitats with their role in bioremediation of different toxic and recalcitrant compounds; persistent organic pollutants, textile dyes, effluents from textile, bleached kraft pulp, leather tanning industries, petroleum, polyaromatic hydrocarbons, pharmaceuticals and personal care products, and pesticides. Bioremediation of toxic organics by fungi is the most sustainable and green route for cleanup of contaminated sites and we discuss the multiple modes employed by fungi for detoxification of different toxic and recalcitrant compounds including prominent fungal enzymes viz., catalases, laccases, peroxidases and cyrochrome P450 monooxygeneses. We have also discussed the recent advances in enzyme engineering and genomics and research being carried out to trace the less understood bioremediation pathways. PMID- 27407291 TI - An In Silico Approach for Identification of the Pathogenic Species, Helicobacter pylori and Its Relatives. AB - Helicobacter is an economically important genus within the phylum Proteobacteria and include many species which cause many diseases in humans. With the conventional methods, it is difficult to identify them easily due to the high genetic similarity among its species. In the present study, 361 16S rRNA (rrs) gene sequences belonging to 45 species of genus Helicobacter were analyzed. Out of these, 264 sequences of 10 clinically relevant species (including Helicobacter pylori) were used. rrs gene sequences were analyzed to obtain a phylogenetic framework tree, in silico restriction enzyme analysis and species-specific conserved motifs. Protein sequences of another housekeeping gene, hsp60 were also subjected to phylogenetic analysis to supplement the data obtained using rrs sequences. Using these approaches, six out of ten species (including H. pylori) were easily segregated, whereas four species namely H. bilis, H. cinaedi, H. felis and Candidatus H. heilmannii were found to be heterogeneous. The above approaches have also helped in segregating unclassified sequences, thus proving them as an easy diagnostic method for identifying members of genus Helicobacter up to species level. PMID- 27407292 TI - Enhancement of Pork Jerky Using Co-cultures of Lactobacillus bulgaricus and Angel Yeast. AB - Strains of Lactobacillus bulgaricus and Angel Yeast were combined to ferment raw pork and make pork jerky. After fermentation, the jerky was dried and then tested for sensory evaluation, pH and free amino acid content. The results showed that the optimal conditions for fermentation using L. bulgaricus and Angel Yeast were: a pH of 6.5, a 1:1 (v/v) ratio of L. bulgaricus to Angel Yeast, a fermentation time of 42 h and temperature of 25 degrees C. The results showed that the pork jerky fermented with the combined strains was not very sour which was close to the pH of 7.0 and had a higher free amino acid content which was more than 68.3 mg/100 g compared with the pork jerky fermented by either L. bulgaricus or Angel Yeast alone. Overall, the results demonstrate that fermentation of raw pork with combined strains of L. bulgaricus and Angel Yeast improves the quality and flavor of pork jerky. PMID- 27407293 TI - Integrative Approach for Producing Hydrogen and Polyhydroxyalkanoate from Mixed Wastes of Biological Origin. AB - In this study, an integrative approach to produce biohydrogen (H2) and polyhydroxyalkanoates (PHA) from the wastes of biological origin was investigated. A defined set of mixed cultures was used for hydrolysis and the hydrolysates were used to produce H2. The effluent from H2 production stage was used for PHA production. Under batch culture, a maximum of 62 l H2/kg of pure potato peels (Total solid, TS 2 %, w/v) and 54 l H2/kg of mixed biowastes (MBW1) was recorded. Using effluent from the H2 production stage of biowaste mixture (MBW1), Bacillus cereus EGU43 could produce 195 mg PHA/l and 15.6 % (w/w). Further, supplementation of GM-2 medium (0.1*) and glucose (0.5 %) in H2 production stage effluents, resulted in significant improvements of up to 11 and 41.7 % of PHA contents, respectively. An improvement of 3.9- and 17-fold in PHA yields as compared to with and without integrative H2 production from the MBW1 has been recorded. This integrative approach seems to be a suitable process to improve the yields of H2 and PHA by mixing biowastes. PMID- 27407294 TI - Bacteriocinogenic Bacteria Isolated from Raw Goat Milk and Goat Cheese Produced in the Center of Mexico. AB - Currently, there are few reports on the isolation of microorganisms from goat milk and goat cheese that have antibacterial activity. In particular, there are no reports on the isolation of microorganisms with antibacterial activity from these products in central Mexico. Our objective was to isolate bacteria, from goat products, that synthesized antimicrobial peptides with activity against a variety of clinically significant bacteria. We isolated and identified Lactobacillus rhamnosus, L. plantarum, L. pentosus, L. helveticus and Enterococcus faecium from goat cheese, and Aquabacterium fontiphilum, Methylibium petroleiphilum, Piscinobacter aquaticus and Staphylococcus xylosus from goat milk. These bacteria isolated from goat cheese were able to inhibit Staphylococcus aureus, Bacillus cereus, Escherichia coli, Listeria monocytogenes, L. inoccua, Pseudomona aeruginosa, Shigella flexneri, Serratia marcescens, Enterobacter cloacae and Klebsiella pneumoniae. In addition, bacteria from goat milk showed inhibitory activity against B. cereus, L. lactis, E. coli, S. flexneri, E. cloacae and K. pneumonia; S. aureus, L. innocua, S. agalactiae and S. marcescens. The bacteriocins produced by these isolates were shown to be acid stable (pH 2-6) and thermotolerant (up to 100 degrees C), but were susceptible to proteinases. When screened by PCR for the presence of nisin, pediocin and enterocin A genes, none was found in isolates recovered from goat milk, and only the enterocin A gene was found in isolates from goat cheese. PMID- 27407295 TI - Vertical Distribution of Bacterial Communities in the Indian Ocean as Revealed by Analyses of 16S rRNA and nasA Genes. AB - Bacteria play an important role in the marine biogeochemical cycles. However, research on the bacterial community structure of the Indian Ocean is scarce, particularly within the vertical dimension. In this study, we investigated the bacterial diversity of the pelagic, mesopelagic and bathypelagic zones of the southwestern Indian Ocean (50.46 degrees E, 37.71 degrees S). The clone libraries constructed by 16S rRNA gene sequence revealed that most phylotypes retrieved from the Indian Ocean were highly divergent from those retrieved from other oceans. Vertical differences were observed based on the analysis of natural bacterial community populations derived from the 16S rRNA gene sequences. Based on the analysis of the nasA gene sequences from GenBank database, a pair of general primers was developed and used to amplify the bacterial nitrate assimilating populations. Environmental factors play an important role in mediating the bacterial communities in the Indian Ocean revealed by canonical correlation analysis. PMID- 27407296 TI - Antagonistic and Biocontrol Potential of Trichoderma asperellum ZJSX5003 Against the Maize Stalk Rot Pathogen Fusarium graminearum. AB - The efficacy of seven strains of Trichoderma asperellum collected from the fields in Southern China was assessed against Fusarium graminearum (FG) the causal agent of corn stalk rot of maize were in vitro for their antagonistic properties followed by statistical model of principal compound analysis to identify the beneficial antagonist T. asperellum strain. The key factors of antagonist activity were attributed to a total of 13 factors including cell wall degrading enzymes (chitnase, protease and beta-glucanases), secondary metabolites and peptaibols and these were analyzed from eight strains of Trichoderma. A linear regression model demonstrated that interaction of enzymes and secondary metabolites of T. asperellum strain ZJSX5003 enhanced the antagonist activity against FG. Further, this strain displayed a disease reduction of 71 % in maize plants inoculated with FG compared to negative control. Pointing out that the T. asperellum strain ZJSX5003 is a potential source for the development of a biocontrol agent against corn stalk rot. PMID- 27407297 TI - Effects of Forest Age on Soil Fungal Community in a Northern Temperate Ecosystem. AB - The polymorphisms of soil fungal rDNA Internal Transcribed Spacer regions were studied in Korean pine forests of various ages (10-100-year-old trees) by means of cloned libraries, and analyzed to determine the effects of the trees' developmental stage on soil fungal community structure. The obtained Shannon diversity index (H) and richness (S) indicated that the diversity of the soil fungal community increased significantly with the development of Korean pines (P < 0.05). In addition, cluster analysis (UPGMA) showed that the soil fungal community variety associated with differently aged Korean pines was higher than 50 %. The soil fungal community diversity correlated significantly with the N content and C/N ratio of the soil (P < 0.05). The results of this study indicate that the age of in Korean pine can affect soil fungal community by altering soil properties, which in turn could affect the nutrient cycling in the forest ecosystem. PMID- 27407298 TI - A Novel Saccharomyces cerevisiae Killer Strain Secreting the X Factor Related to Killer Activity and Inhibition of S. cerevisiae K1, K2 and K28 Killer Toxins. AB - It was determined that Kx strains secrete an X factor which can inhibit all known Saccharomyces cerevisiae killer toxins (K1, K2, K28) and some toxins of other yeast species-the phenomenon not yet described in the scientific literature. It was shown that Kx type yeast strains posess a killer phenotype producing small but clear lysis zones not only on the sensitive strain alpha'1 but also on the lawn of S. cerevisiae K1, K2 and K28 type killer strains at temperatures between 20 and 30 degrees C. The pH at which killer/antikiller effect of Kx strain reaches its maximum is about 5.0-5.2. The Kx yeast were identified as to belong to S. cerevisiae species. Another newly identified S. cerevisiae killer strain N1 has killer activity but shows no antikilller properties against standard K1, K2 and K28 killer toxins. The genetic basis for Kx killer/antikiller phenotype was associated with the presence of M-dsRNA which is bigger than M-dsRNA of standard S. cerevisiae K1, K2, K28 type killer strains. Killer and antikiller features should be encoded by dsRNA. The phenomenon of antikiller (inhibition) properties was observed against some killer toxins of other yeast species. The molecular weight of newly identified killer toxins which produces Kx type strains might be about 45 kDa. PMID- 27407299 TI - Isolation, Identification and Characterization of Two Aluminum-Tolerant Fungi from Acidic Red Soil. AB - Acidic red soil from a forest in Jiangxi Province was selected to isolate aluminum (Al)-resistant microbes, from which eight fungi were isolated. Two strains (S4 and S7) were found to be extremely tolerant to Al concentrations of up to 550 mmol L(-1) and could grow at low pH levels (3.20-3.11). Morphological and 26S rDNA sequence analyses indicated that strain S4 belonged to Eupenicillium, while strain S7 was an unclassified Trichocomaceae. Further investigation showed that both strains were endowed with the ability to resist Al; strain S4 accumulated such a substantial amount of Al that its growth was limited to a larger extent than strain S7. The lower amounts of Al adsorbed in the mycelium and the much larger amounts of Al retained in the medium, in addition to the color change of the culture solution, implied that these two strains may resist Al by preventing Al from entering the cell and by chelating Al by secreting unique metabolites outside of the cell. PMID- 27407300 TI - Characterization of Chromium Waste Form Based on Biocementation by Microbacterium sp. GM-1. AB - This paper demonstrated a biocementation technology for chromium slag by strain GM-1, a calcifying ureolytic bacterium identified as Microbacterium, based on microbially induced calcium carbonate. The characterization of Microbacterium sp. GM-1 was assessed to know the growth curve in different concentrations of Cr(VI). Microbacterium sp. GM-1 was tolerant to a concentration of 120 mg/L Cr(VI). Chromium waste forms were prepared using chromium, sand, soil and bacterial culture. There we had three quality ratios (8:2:1; 8:1:1; 8:2:0.5) of material (chromium, sand and soil, respectively). Bacterial and control chromium waste forms were analyzed by thermal gravimetric analyzer. All bacterial forms (8:2:1; 8:1:1; 8:2:0.5 J) showed sharp weight loss near the decomposition temperature of calcium carbonate between 600 and 700 degrees C. It indicated that the efficient bacterial strain GM-1 had induced calcium carbonate precipitate during bioremediation process. A five step Cr(VI) sequential extraction was performed to evaluate its distribution pattern in chromium waste forms. The percentage of Cr(VI) was found to significantly be decreased in the exchangeable fraction of chromium waste forms and subsequently, that was markedly increased in carbonated fraction after biocementation by GM-1. Further, compressive strength test and leaching test were carried out. The results showed that chromium waste forms after biocementation had higher compressive strength and lower leaching toxicity. Additionally, the samples made of 8:1:1 (m/m/m) chromium + sand + soil were found to develop the highest compressive strength and stand the lowest concentration of Cr(VI) released into the environment. PMID- 27407301 TI - Proteomic Investigation of Photorhabdus Bacteria for Nematode-Host Specificity. AB - Majority of animals form symbiotic relationships with bacteria. Based on the number of bacterial species associating with an animal, these symbiotic associations can be mono-specific, relatively simple (2-25 bacterial species/animal) or highly complex (>10(2)-10(3) bacterial species/animal). Photorhabdus (family-Enterobacteriaceae) forms a mono-specific symbiotic relationship with the entomopathogenic nematode Heterorhabditis. This system provides a tractable genetic model for animal-microbe symbiosis studies. Here, we investigated the bacterial factors that may be responsible for governing host specificity between nematode and their symbiont bacteria using proteomics approach. Total protein profiles of P. luminescens ssp. laumondii (host nematode- H. bacteriophora) and P. luminescens ssp. akhurstii (host nematode- H. indica) were compared using 2-D gel electrophoresis, followed by identification of differentially expressed proteins by MALDI-TOF MS. Thirty-nine unique protein spots were identified - 24 from P. luminescens ssp. laumondii and 15 from P. luminescens ssp. akhurstii. These included proteins that might be involved in determining host specificity directly (for e.g. pilin FimA, outer membrane protein A), indirectly through effect on bacterial secondary metabolism (for e.g. malate dehydrogenase Mdh, Pyruvate formate-lyase PflA, flavo protein WrbA), or in a yet unknown manner (for e.g. hypothetical proteins, transcription regulators). Further functional validation is needed to establish the role of these bacterial proteins in nematode-host specificity. PMID- 27407303 TI - Isolation of Mexican Bacillus Species and Their Effects in Promoting Growth of Chili Pepper (Capsicum annuum L. cv Jalapeno). AB - The purpose of this work was to isolate and identify native bacteria from plants collected in the State of Yucatan, Mexico with the ability to promote growth of chili pepper (Capsicum annuum L. cv Jalapeno). We identified nine bacterial isolates that belong to five species of Bacillus (i.e. Bacillus subtilis, B. flexus, B. cereus, B. megaterium and B. endophyticus) that produced indoleacetic acid (4.0-24.3 ug/mL) with solubilization index of 1.3-1.6. All the bacterial isolates were evaluated based on their ability to promote growth of chili pepper. Plants inoculated with B. subtilis ITC-N67 showed an increase in stem diameter and root volume, whereas inoculation with B. cereus ITC-BL18 increased the number of flower buds, fresh biomass of roots and total fresh biomass. Conversely, B. flexus ITC-P4 and B. flexus ITC-P22 showed deleterious effect on root volume and total biomass. In summary, our data showed that native B. cereus TC-BL18 and B. subtilis ITC-N67 have potential to be used as growth promoting microorganism for chili pepper, particularly in the state of Yucatan, Mexico. PMID- 27407302 TI - Role of Indole Production on Virulence of Vibrio cholerae Using Galleria mellonella Larvae Model. AB - Cell to cell communication facilitated by chemical signals plays crucial roles in regulating various cellular functions in bacteria. Indole, one such signaling molecule has been demonstrated to control various bacterial phenotypes such as biofilm formation and virulence in diverse bacteria including Vibrio cholerae. The present study explores some key factors involved in indole production and the subsequent pathogenesis of V. cholerae. Indole production was higher at 37 degrees C than at 30 degrees C, although the growth at 37 degrees C was slightly higher. A positive correlation was observed between indole production and biofilm formation in V. cholerae. Maximum indole production was detected at pH 7. There was no significant difference in indole production between clinical and environmental V. cholerae isolates, although indole production in one environmental isolate was significantly different. Both growth and indole production showed relevant changes with differences in salinity. An indole negative mutant strain was constructed using transposon mutagenesis and the direct effect of indole on the virulence of V. cholerae was evaluated using Galleria mellonella larvae model. Comparison to the wild type strain, the mutant significantly reduced the mortality of G. mellonella larvae which regained its virulence after complementation with exogenous indole. A gene involved in indole production and the virulence of V. cholerae was identified. PMID- 27407304 TI - Comparison of DOT-ELISA and Standard-ELISA for Detection of the Vibrio cholerae Toxin in Culture Supernatants of Bacteria Isolated from Human and Environmental Samples. AB - A comparison of DOT-ELISA and Standard-ELISA was made for detection of Vibrio cholerae toxin in culture supernatants of bacteria isolated from human and environmental samples. A total of 293 supernatants were tested in a double blind assay. A correlation of 100 % was obtained between both techniques. The cholera toxin was found in 20 Inaba and 3 Ogawa strains. Positive samples were from seafood (17 samples), potable water (1 sample) and sewage (5 samples). The DOT ELISA was useful as the standard-ELISA to confirm the presence of cholera toxin in the environmental samples. PMID- 27407305 TI - ENDOSKELETAL PROSTHESIS: A NEW ERA FOR AMPUTEE. PMID- 27407306 TI - PATIENT SATISFACTION IN PROSTHETIC REHABILITATION PROGRAMME. AB - Patient satisfaction is an important outcome measure independent of other outcomes. Its measurement is important to assess the effectiveness of a programme and to gain insight into the patients' perception of the programme. In this study conducted in a large rehabilitation centre it was found that majority of patients express satisfaction with care inspite of perceived discomfort. Various demographic factors, severity or duration of the disability or the level of rehabilitation do not influence patient satisfaction. Patients express more concern with aspects such as delay in issue of the prosthesis, or hotel component of the hospital services. Patients did not appear too concerned about the level of information provided. Patient satisfaction is an individual reaction to the overall care process and is influenced by the initial expectation level of the patient. Emotional response of the patient appears to be more important determinant of patient satisfaction than the cognitive evaluation. Periodical assessment of patient satisfaction should be an important component of any programme evaluation exercise. PMID- 27407307 TI - ARTHROSCOPIC EVALUATION AND MANAGEMENT OF MENISCAL INJURIES OF THE KNEE. AB - 50 cases of isolated meniscal injuries of the knee were evaluated and managed arthroscopically. 56% of the cases were in 25-35 year age group. In 80% of the cases military training and contact sports was the mode of injury. Maximum (42%) patients reported late (> 2 years) after the injury. On presentation, they had an average Lysholm knee score of 53.76. Medial meniscal lesion was seen in 74%. Commonest pattern of tear encountered was a longitudinal tear (40%). Depending on pattern and extent of lesion, partial meniscectomy (60%), subtotal meniscectomy (14%) and total meniscectomy (26%) were performed. Patients were followed up at six months and one year. The average Lysholm score at 6 months was 83.3 and at one year 79.5. At one year, the patient satisfaction level was 82% and patients who underwent partial meniscectomy had the best results. PMID- 27407308 TI - USEFULNESS OF EVALUATION OF ANTIMEASLES ANTIBODIES IN PRETERM BABIES. AB - As per WHO recommendations, measles vaccine is administered at the age of 9 months which is based on studies demonstrating seroconversion (from positive to negative) at this age. However this contention may not hold good in preterm babies since they may have lower initial levels of passively transferred IgG antimeasles antibodies of maternal origin. To explore this possibility, 50 preterm babies (gestational age less than 37 weeks) were studied for antimeasles antibodies. Serum samples were collected at birth and then at 3 months and 5 months of age in all the cases. Antimeasles antibody assay was done in all the serum samples using ELISA kits. At birth 32% of infants were positive for antimeasles antibodies whereas 60% were weakly positive and 8% were negative. At 3 months of age 50% were sero negative, 2% positive and 40% weakly positive. The sero negativity was found to be 98% at 5 months with only 2% remaining positive. Since seroconversion is seen to occur in this vast majority of preterm infants at the age of 5 months, antimeasles vaccine should be administered at this age to this subset of more vulnerable babies. PMID- 27407309 TI - INDUCTION OF LABOUR WITH MISOPROSTOL - A PROSTAGLANDIN E1 ANALOGUE. AB - The purpose of our study was to compare the safety and efficacy of intravaginal misoprostol versus existing hospital protocol of intracervical dinoprostone and oxytocin for cervical ripening and induction of labour. 200 patients with indication for induction of labour were randomly assigned to receive either intravaginal misoprostol or dinoprostone/oxytocin combination. In first group twenty five micrograms of misoprostol was placed intravaginally every 6 hours till the patient reached active stage of labour. In second group dinoprostone gel 0.5 mg was placed in the endocervix at night and oxytocin induction was started in the early morning. The average interval from start to induction of vaginal delivery was shorter in misoprostol group (1315+/-811 minutes) compared to dinoprostone/oxytocin group (1512+/-712 minutes) (p < 0.01). There was no significant difference in route of delivery. 18% of misoprostol treated patients and 23% of dinoprostone/oxytocin treated patients required Caesarean section. Complications such as uterine tachysystole were significantly higher in misoprostol group (p < 0.01) but it was not associated with increased incidence of uterine hyperstimulation. Perinatal outcome was similar in both groups. PMID- 27407310 TI - A CORRELATIVE STUDY OF MATERNAL HAEMOGLOBIN AND BIRTH WEIGHT. AB - This prospective, cross sectional population study was carried out to determine the relationship between maternal haemoglobin concentration and birth weight in different socioeconomic groups in a tertiary care teaching hospital. 500 cases each from two teaching hospitals about whom information on socioeconomic status, haemoglobin concentration and birth weight was known were included in the study. This was a stratified random study based on the preselected inclusion and exclusion criteria. 149 (14.9%) women belonged to upper socioeconomic group, 119 (11.9%) to upper middle, 125 (12.5%) to lower middle, 90 (9.0%) to upper lower and 517 (51.7%) to lower group. Mean haemoglobin level was found to be lower in low socioeconomic group as compared to high socioeconomic group and was statistically significant (F value of 18.2521 & p 0.000). The lowest Hb level was 4.0g/dl and highest was 15.0g/dL Majority of pregnant women (89.3%) had their lowest haemoglobin level during the second trimester as compared to first trimester (0.8%) and third trimester (9.9%). The mean birth weight in upper socioeconomic group was 2.7508 kg, 2.7556 kg in upper middle group, 2.8802 kg in lower middle group, 2.7876 kg in upper lower group and 2.7515 in lower socioeconomic group. By analysis of variance test it was found that the mean birth weight did not vary significantly between different socioeconomic groups with an F value of 1.3398 and p value of 0.2450. The correlation analysis of haemoglobin concentration with birth weight suggested that for every rise of haemoglobin concentration by 1.0g/dl the birth weight reduced by 03839 kg (highly significant p < 0.001). In the present study there was significant inverse relationship of maternal haemoglobin concentration to birth weight Results are in agreement with the hypothesis that a higher blood viscosity is a risk factor for sub optimal placenta-perfusion. PMID- 27407311 TI - HYSTEROSCOPY IN POSTMENOPAUSAL BLEEDING. AB - The purpose of the present study was to evaluate the utility of hysteroscopy as a diagnostic tool in cases of postmenopausal bleeding. The study includes 42 cases presenting with postmenopausal bleeding on which hysterscopy was performed using rigid hysteroscope (CIRCON) with glycine 1.5% as the distension medium. In 17 of the 42 cases positive hysteroscopic findings were noted which included 2 cases of endometrial carcinoma, 2 cases of postmenopausal endometritis, 4 cases of endometrial polyp, 5 cases of endometrial hyperplasia, 1 case of submucous myoma and 3 cases of endocervical polyp whereas normal postmenopausal endometrium was noticed in rest of the 25 cases. Endometrial biopsy was done in all these cases so that the hysteroscopic findings could be corroborated with tissue diagnosis. Hysteroscopy along with directed endometrial biopsy proved to be a useful diagnostic aid in cases of postmenopausal bleeding. PMID- 27407312 TI - PROBLEMS IN MANAGEMENT OF KALA AZAR: EXPERIENCE FROM BIHAR. AB - 35 cases of Kala-Azar were managed at 200 bedded peripheral hospital, Bihar from Jan 1994 to Jan 1998. Patients presenting with history of fever for more than 3 weeks duration with splenomegaly or hepatosplenomegaly were investigated for Kala Azar. A confirmative diagnosis of Kala-Azar was made in all cases by demonstrating Leishmania amastigote (LD body) in bone marrow or splenic aspirate. All patients were initially treated by sodium stibogluconate (SSG) 20 mg/kg body wt daily for 20 to 40 days depending on response. SSG induced cardiac toxicity was seen in 6 cases (VT-2, ST-T changes-2, QTc Prolongation-2) out of which 1 patient died of refractory ventricular tachyacarida. 9 patients were unresponsive to SSG,8 patients were treated with pentamidine isoethionate (4 mg/kg body wt IV alternate day) 10-15 dosage. 1 patient was treated with amphotericin-B. All the patients showed clinical and parasitological improvement and no relapse was noted at 6 month follow up. 6 patients had associated tuberculosis (Disseminated TB-2, Miliary TB-1, Pulmonary TB-1. Pleural TB-2). 2 patients had associated pneumonia, 1 patient had HIV infection and 1 patient had erythema nodosum leperosum. PMID- 27407314 TI - PRENATAL DIAGNOSIS OF NEURAL TUBE DEFECTS. AB - 14 cases of neural tube defect (NTD) were detected on screening of 1950 pregnant women over a period of 30 months by antenatal ultrasonography (USG) examination, suggesting an incidence of 7.1 per thousand conceptions. The distribution of types of NTD were occult dysraphism 14%, meningocele 14%, myelocele 7%, myelomeningocele 14%, encephalocele 14% and anencephaly 37%. The study established high accuracy of USG screening for antenatal diagnosis of NTD with sensitivity of 85.71% and specificity of 100. PMID- 27407313 TI - IS BETA CELL DYSFUNCTION RESPONSIBLE FOR FLAT GLUCOSE TOLERANCE CURVE IN PRIMARY HYPOTHYROIDISM? (A HYPOTHESIS). AB - An intimate relationship between thyroid hormones and carbohydrate metabolism has long been recognised and oral glucose load produces flat glucose tolerance curve in patients with primary hypothyroidism. Although delayed glucose absorption was proposed to explain flat glucose tolerance curve exact mechanism remains to be elucidated. Hence this study was undertaken to assess glucose and insulin response to OGTT and IVGTT in 25 freshly detected cases of hypothyroidism and 25 healthy control. The cases were matched for sex, age, BMI, and waist hip ratio with controls. Cases and controls with past or family history of obesity, diabetes mellitus, or hypertension were excluded from study. The biochemical profile of the cases and controls was also comparable except for haemoglobin (11.2+/-0.31 vs 12.9+/-0.22 gm/dl)(p=0.0004). Serum cholesterol and triglyceride levels were higher in the cases but difference was not statistically significant Fasting plasma glucose level was significantly lower in hypothyroid patients (78+/-2.2 vs88+/-4.4 mg/dl, p=0.049). The oral glucose tolerance curve was flat with plasma glucose levels significantly lower at 30 minutes. The insulin levels during OGTT were found to be higher in the cases at all stages. There was loss of first phase insulin response to the glucose load during the IVGTT, which was blunted at all stages and the difference was statistically significant at 0 and 3 minutes. Loss of first phase insulin response to IV glucose suggests that there is evidence of beta-cell dysfunction. Patients with hypothyroidism were more insulin sensitive than control and insulin secretion was comparable with controls. Therefore flat glucose tolerance curve can be explained by absence of insulin priming effect leading to decreased glucose absorption followed by increased glucose disposal because of higher insulin levels following OGTT and increased glucose disposal caused by increased insulin sensitivity. PMID- 27407315 TI - STATINS & NEWER HOPE FOR ATHEROSCLEROSIS ASSOCIATED DISEASES. PMID- 27407316 TI - ERRATUM. AB - [This corrects the article DOI: 10.1016/S0377-1237(01)80101-5.]. PMID- 27407317 TI - OXYGEN TOXICITY. AB - Oxygen, the gas vital to sustain life, can also destroy it. It may become toxic at an elevated partial pressure, which may be the result of a rise in inspired oxygen concentration, an increase in environmental pressure or a combination of both. The toxicity tends to express itself most recognizably in one of several forms including central nervous system manifestations, pulmonary signs and symptoms and ocular effects, especially in premature infants. Other forms of toxicity should be expected in severe exposure but are difficult to detect and hence are not often considered important limitations for the use of oxygen. The onset and degree of the toxicity vary with the concentration of the gas used and the duration of exposure. Marked variations in individual susceptibility are found. Prevention of its occurrence and early detection of toxicity are called for, the treatment being symptomatic. PMID- 27407318 TI - PROSTAGLANDINS IN CONGENITAL HEART DISEASE. PMID- 27407319 TI - INTEGRATED CHILD DEVELOPMENT SERVICES (ICDS) SCHEME. AB - Integrated Child Development Services (ICDS) scheme is world's largest community based programme. The scheme is targeted at children upto the age of 6 years, pregnant and lactating mothers and women 16-44 years of age. The scheme is aimed to improve the health, nutrition and education (KAP) of the target community. Launched on 2 October 1975, the scheme has completed 25 years of its operational age. The article describes in brief, the organisation, achievements and drawbacks of this national programme. It also suggests various thrust areas for its betterment and further improvement. PMID- 27407320 TI - AN INTRODUCTION TO ESSENTIALS OF BIO-MEDICAL WASTE MANAGEMENT. AB - The issue of biomedical waste management has assumed great significance in recent times particularly in view of the rapid upsurge of HIV infection. Government of India has made proper handling and disposal of this category of waste a statutory requirement with the publication of gazette notification no 460 dated 27 July 1998. The provisions are equally applicable to our service hospitals and hence there is a need for all the service medical, dental, nursing officers, other paramedical staff and safaiwalas to be well aware of the basic principles of handling, treatment and disposal of biomedical waste. The present article deals with such basic issues as definition, categories and principles of handling and disposal of biomedical waste. PMID- 27407321 TI - SENGSTAKEN - BLACKMORE TUBE. PMID- 27407322 TI - MULTIDRUG - RESISTANT TUBERCULOSIS (MDRTB) IN CHILDREN. PMID- 27407323 TI - MALIGNANT TRANSFORMATION IN A YOUNG ADULT WITH RECURRENT LARYNGEAL PAPILLOMATOSIS. PMID- 27407324 TI - MYCOTIC BRACHIAL ARTERY ANEURYSM FOLLOWING A PERIANAL ABSCESS. PMID- 27407325 TI - PAIN ABDOMEN AT EXTREME ALTITUDES: SINISTER IMPLICATIONS. AB - 2 cases of portal, splenic and superior mesenteric vein thromboses related to prolonged stay at high altitude are presented. Both presented initially with innocuous appearing vague pain in abdomen with no physical signs. Later hepatosplenomegaly, and pleural effusion (left) was also detected. Diagnosis was based on CT scan and colour Doppler study showing thrombosed veins and porto systemic collateral. 1 patient developed a large splenic haematoma requiring splenectomy. Both were managed with early anticoagulation and have done well in the short follow up. PMID- 27407326 TI - AN UNUSUAL FOREIGN BODY IN THE BRONCHUS. PMID- 27407327 TI - MADURA FOOT. PMID- 27407328 TI - THORACIC NEUROBLASTOMA WITH SPONTANEOUS REMISSION. PMID- 27407329 TI - UNUSUAL BILIARY FISTULA. AB - Agenesis of gall bladder is a clinical rarity, as most of the diagnoses are made at autopsy. Preoperative diagnosis of this anomaly is fraught with follies. External biliary fistulae are usually result of complications of trauma or biliary surgery. Internal fistulae on the other hand may result from erosion of wall by a stone, cancerous growth or peptic ulcer. Sites of opening of internal fistulae are stomach, duodenum, jejunum, ileum or colon. These should be suspected if gas shadows are seen in biliary tree. PMID- 27407330 TI - MACROGLOSSIA: A RARE CLINICAL ENTITY. PMID- 27407331 TI - AMNIOTIC BAND SYNDROME. PMID- 27407332 TI - LEIOMYOMA OF OESOPHAGUS (A Report on Two Cases). PMID- 27407333 TI - ABNORMAL CYTOLOGY REPORT AND FURTHER MANAGEMENT OF PRECANCEROUS LESION: EFFECT OF CHANGE TO TBS. PMID- 27407334 TI - TROPICAL PULMONARY EOSINOPHILIA: NOCTURNAL SYMPTOMS. PMID- 27407335 TI - ABNORMAL CYTOLOGY REPORT AND FURTHER MANAGEMENT OF PRECANCEROUS LESION: EFFECT OF CHANGE TO TBS: Reply. PMID- 27407336 TI - SUPRASELLAR PAPILLARY SQUAMOUS EPITHELIOMA (PAPILLARY CRANIOPHARYNGIOMA): Reply. PMID- 27407337 TI - CANCER SCREENING CAMP: OUR EXPERIENCE. PMID- 27407338 TI - SUPRASELLAR PAPILLARY SQUAMOUS EPITHELIOMA (PAPILLARY CRANIOPHARYNGIOMA). PMID- 27407339 TI - LOW BACKACHE: OVER REPORTED BUT UNDERDIAGNOSED? PMID- 27407340 TI - SUBTOTAL THYROIDECTOMY IN THE MANAGEMENT OF GRAVE'S DISEASE. AB - Treatment options for Grave's disease include radio-iodine ablation, which is the standard treatment in the USA, antithyroid drug therapy, which is popular in Japan, and surgery, which is commonly employed in Europe and India. There are very few reports about the outcome of surgery in Grave's disease in the Indian setting. Surgery for Grave's disease is an attractive option in under developed countries to cut short prolonged drug treatment, costly follow up and avoid the need for radio-isotope facilities for 1311 ablation. Aim of the present study was to assess the result of subtotal thyroidectomy in 32 cases of Grave's Disease referred for surgery by the endocrinologist in a teaching hospital. Patients were prepared for surgery with Lugol's iodine and propranalol. Subtotal thyroidectomy was performed by a standard technique, which included dissection and exposure of recurrent laryngeal nerves and parathyroid glands. Actual estimation of weight of the remnant gland was not part of the study. Duration of follow up ranged from 6 months to 4 years. 13 of 32 cases were males. Age ranged from 20 to 57 years. There was 1 death in the immediate post-operative period. There were no cases of permanent hypoparathyroidism or recurrent laryngeal nerve palsy. 1 patient developed temporary hypoparathyroidism. 1 patient developed recurrence of hyperthyroidism and 3 cases developed hypothyroidism all within 2 years of surgery. The study has demonstrated the safety and effectiveness of surgery for Grave's Disease in comparison to the reported high incidence of hypothyroidism following radio-iodine therapy and high recurrence rate after anti thyroid drug therapy. PMID- 27407341 TI - MANAGEMENT OF CONCURRENT GLAUCOMA AND CATARACT BY PHACOTRABECULECTOMY TECHNIQUE: AN EFFECTIVE ALTERNATIVE APPROACH. AB - 30 cases of open angle glaucoma with cataract who underwent phacoemulsification, PMMA phaco profile IOL implantation and trabeculectomy through same incision were critically evaluated. The mean controlled, preoperative intra ocular pressure was 20 mm of Hg (range 18 to 35 mm of Hg) by aplanation method. Mean post operative pressure after 12 months was 13 mm of Hg (range 11 to 22 mm of Hg) intra operative hyphaema, post operative uveitis were noted problems. Periodic, post operative optic disc and field evaluation remained static in 66% cases. Visual acuity of 6/12 or better was achieved in 60% cases. Failure to restore glaucoma control without medication was seen in 13.3% cases after 9-12 months. The combined phacotrabeculectomy is an effective single step technique of managing concurrent glaucoma with cataract. PMID- 27407342 TI - OVARIAN HYPERSTIMULATION SYNDROME DURING INDUCTION OF OVULATION FOR INTRA UTERINE INSEMINATION. AB - Ovarian Hyperstimulation Syndrome (OHSS) is a known iatrogenic complication of ovulation induction. Our experience of such complication while managing basic assisted conception cycles has been analysed in the present study. 12 such cases were identified in 976 cycles studied giving an overall incidence of 1.22%. All the cases were of mild to moderate variety and were managed conservatively. The duration of the complication ranged between 10 days to 6 weeks. Polycystic ovarian disease, LH: FSH ratio of more than 1, presence of four or more secondary follicles were found to be important predictive criteria. Identification of predictive factors of OHSS can be helpful in taking due care while using ovulation inducing drugs. Conception does worsen OHSS, but termination is usually not necessary. PMID- 27407343 TI - "CYBERMEDICINE AND CYBERHEALTHCARE" REVIEW OF MEDICINE ON THE INTERNET. PMID- 27407345 TI - TECHNOLOGY UPDATE: PINLESS EXTERNAL FIXATOR. AB - Pinless fixator is an outstanding system designed for external fixation without invading the medullary canal in polytrauma patients. The pinless external fixation allows immediate stabilization and reduction of compound tibial fractures with or without skin loss. This is an ideal tool for emergency stabilization of tibial fractures in a peripheral setup because the application technique is easy to learn by general surgeons. This device can be applied quickly even under local anaesthesia, average application time being 20 minutes in our setup. It does not transfix the bone and therefore avoids the contamination of the medullary canal and thus does not preclude the use of any further treatment methods eg. repeated wound debridement, soft tissue coverage and internal fixation of the fracture. Transportation to referral centre can be done after application of the external fixator if considered necessary in patients with multiple injuries. PMID- 27407344 TI - VACCINES - WHAT'S NEW? PMID- 27407346 TI - SPASMUS NUTANS. PMID- 27407347 TI - SCLEROSING HAEMANGIOMA OF LUNG PRESENTING AS SPONTANEOUS HAEMOTHORAX. PMID- 27407348 TI - TEMPORAL BONE FRACTURE WITH FACIAL NERVE PALSY. PMID- 27407349 TI - AN UNUSUAL CASE OF REFRACTORY HYPOTENSION FOLLOWING SPINAL ANAESTHESIA. PMID- 27407350 TI - POLYTRAUMA: OCCASIONAL DILEMMA FOR THE SINGLE SURGEON. PMID- 27407351 TI - PSYCHIATRY IN THE NEW MILLENNIUM. PMID- 27407352 TI - LATERAL APPROACH : A BETTER TECHNIQUE FOR SPINAL ANAESTHESIA IN THE MODERN ERA. AB - The most commonly used technique in routine spinal anaesthesia practice is the midline approach, compared to the lateral or paramedian approach. With the better understanding of the technique and introduction of fine gauge spinal needles, this practice needs a rethinking. Lateral approach was used in 60 patients undergoing different surgical procedures below the umbilicus, using 24 or 25 gauge, Quincke spinal needle without an introducer. The result was gratifying. In 77% of the cases the subarachnoid space could be entered in the first attempt. There was no failure. No patient complained of postdural puncture headache or post operative backache. Only one patient reported paraesthesia during needle placement without any residual effect. Various other advantages of the technique are discussed. Thus with due practice, lateral approach is found to be superior in modern day spinal anaesthesia. PMID- 27407353 TI - PSYCHIATRIC EVALUATION OF LIMB FRACTURE PATIENTS. AB - The study included 70 consecutive patients with fracture of the lower and upper limbs each and an equal number of age and sex matched normal control subjects. All the subjects were screened using the General Health Questionnaire (GHQ), the Michigan Alcoholism Screening Test (MAST), Carroll Rating Scale for Depression (CRSD), State-Trait Anxiety Inventory (STAI), Impact of Events Scale (IES), Fatigue Scale (FS) and the Perceived Stress Questionnaire (PSQ). Probable "Psychiatric cases" identified by the questionnaires underwent diagnostic psychiatric evaluation. As compared to normal controls, the limb fracture patients obtained significantly higher scores on the GHQ, MAST, CRSD, IES & FS but not on the STAI & PSQ. Psychiatric evaluation revealed significantly higher prevalence of psychiatric disorders in lower limb fracture patients (n=31) as compared to upper limb fracture patients (n=18) and control subjects (n=6). Limb fracture patients had a high prevalence of alcohol dependence/abuse (243%) and depressive disorders (6.4%). The results indicate that psychological intervention would greatly facilitate the management of these patients. PMID- 27407354 TI - SHOULDER DYSTOCIA : OBSTETRICIAN'S NIGHTMARE. AB - Shoulder dystocia is an uncommon complication of delivery. 12 cases of shoulder dystocia are presented. The study suggests that prediction of shoulder dystocia on the basis of clinical profile is difficult A high index of suspicion is to be maintained in the presence of certain risk factors such as multigravida with large baby having prolonged 1(st) (decelarative phase) and 2(nd) stage of labour necessitating instrumental delivery. High neonatal morbidity (brachial palsy 44% and low Apgar score 44%) was found to be associated with shoulder dystocia. Among the manoeuvres used for the delivery of impacted shoulder, no neonatal injuries were associated with successful McRoberts manoeuvre. However, the success rate of the procedure was only 50%. Fundal pressure in absence of other manoeuvres resulted in 100% complication rate, hence should be condemned. PMID- 27407355 TI - PERSONALITY FACTOR CORRELATES OF GROWTH HORMONE AND HYPOTHERMIC RESPONSE TO BUSPIRONE CHALLENGE IN SUICIDAL SOLDIERS. AB - The biological underpinnings of suicidal behaviour and possible rational pharmacotherapy of persons exhibiting such behaviour is the focus of this study. The study was conducted on 25 male Armed Forces personnel who attempted suicide and 25 matched healthy controls. Hypothermic and Growth Hormone response to Buspirone challenge was measured serially. 11 cases of attempted suicide had subsensitive postsynaptic 5 HT-1A receptors as indicated by blunted Growth Hormone response, while in other suicidal soldiers hypothermic response was markedly blunted indicating subsensitive presynaptic 5HT-IA receptors in the latter. Personality factor assessment carried out by 16 personality factor test, indicated overt extraversion marks for subsensitive postsynaptic 5 HT-IA receptors, while overt intraversion marks for subsensitive presynaptic 5 HT-IA receptors, in suicidal soldiers. In the light of the above, therapeutic options of Serotonin reuptake inhibition, agonist load at presynaptic 5 HT-IA and reciprocal stimulation of postsynatpic 5 HT-IA receptors for prevention of future attempts and completed suicides is discussed. PMID- 27407356 TI - DO PERSONALITY FACTORS DETERMINE THE CHOICE OF PROFESSION? AN EXPLORATIVE STUDY OF FEMALE NURSING AND FEMALE MEDICAL STUDENTS. AB - Medical profession and nursing profession are noble professions. Both professions place heavy emphasis on desirable personality traits of being affectionate, humble and responsible. Personal qualities such as integrity, responsibility and empathy have often been mentioned in the literature as desirable qualities for these professions. The present study was planned to explore these personal attributes. Sample for the study consisted of 26 female medical students of first year MBBS and 29 female nursing students of first year B.Sc. Nursing course. The subjects were matched for age and sex. Personality profile was evaluated by administering 16 Personality Factor Form A. Findings revealed significant differences on factor 'A', 'F', 'H' and 'M'. On second order factors significant differences were noted on introversion-extroversion and independence-subduedness dimension. PMID- 27407357 TI - ACCURACY OF SERUM - ASCITES ALBUMIN GRADIENT IN THE AETIOLOGICAL DIAGNOSIS OF ASCITES. AB - 50 adults with ascites admitted to our hospital were studied. Simultaneous samples of ascitic fluid and blood were collected and subjected to analysis including ascitic fluid total protein and serum ascites albumin gradient The cut off value of serum-ascites albumin gradient for differentiating between high and low gradient was taken as 1.1 gm % and of ascitic fluid protein for differentiating exudate and transudate as 2.5 gm%. The sensitivity, specificity, positive predictive value and negative predictive value of high gradient and transudative ascites in diagnosing portal hypertension were 943%, 60%, 84.6%, 81.8% and 62.9%, 133%, 91.7% and 50% respectively. High gradient ascites is a sensitive test in the diagnosis of portal hypertension as a cause of ascites. The exudate-transudate approach has severe limitations in the differential diagnosis of ascites. PMID- 27407358 TI - PROLONGED FEVER DURING THE TREATMENT OF PULMONARY TUBERCULOSIS. AB - A study was carried out to investigate the causes of prolonged fever or onset of fever, after starting anti-tubercular treatment (ATT) in sputum smear positive, HIV negative patients admitted in a Tuberculosis (TB) Sanatorium for directly observed therapy (DOT). A total of 40 patients were studied. All were males with age ranging from 22-55 years (mean 43 years). There were 22 (55%) patients with radiological extensive disease, 12 (30%) of whom had toxemia of TB (any three of the following, <90% body weight, hypoalbuminemia, hyponatremia, severe normocytic anaemia, <5mm response on tuberculin testing). Radiologically, moderately extensive disease was seen in 9 (22.5%) cases, whereas focal disease was present in another 9 (22.5%) patients. There were 28 (70%) patients who had evidence of dissemination of disease to extra pulmonary organs. It was found that fever occurred because of direct complications of TB in 22.5%, TB hypersensitivity (cold abscess) in 12.5%, drug resistance in 10% and drug reactions in 22.5%. Other diseases were the cause of fever in 32.5%. These included superadded lung infections in 15%, malaria in 7.5% anaemia in 5%. Filariasis and amoebic liver abscess in another 2.5% each. It is concluded that such fevers require a systematic and detailed investigation rather than attributing fever to drug resistance or TB toxemia alone. PMID- 27407359 TI - A STRATEGY FOR RAPID IDENTIFICATION OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS NASAL CARRIER STATUS. AB - Methicillin Resistant Staphylococcus aureus (MRSA) is a multi drug resistant organism responsible for severe outbreaks of life threatening infections in hospitals which are difficult to treat They are spread by nasal carriage among the hospitalised patients, staff and visitors. Mannitol cloxacillin salt agar (MCSA) is a single tube method to identify MRSA. However, tubes showing growth and change in colour on biochemical characterisation often do not prove to be MRSA. In this study we have combined two strategies for the rapid identification and isolation of MRSA by culture in MCSA and multiplex PCR for mecA and femB genes. Anterior nasal swabs obtained from nursing staff and patients admitted to a large referral hospital, were inoculated into MCSA. Of the 100 tubes inoculated, 8 tubes showed change in colour and growth. On conventional testing 4 were MRSA, 3 were methicillin sensitive S aureus (MSSA) and 1 was Methicillin Sensitive Coagulase Negative S aureus (MSCNS). Genotyping by multiplex PCR revealed 5 MRSA, 2 MSSA and 1 MRCNS. The Multiplex PCR technique to rapidly identify presence of mecA and femB genes showed presence of both mecA and femB bands in all MRSA. The methicillin sensitive organisms showed absence of mecA gene while coagulase negative organisms showed absence of the fern B gene. Combining MSCA with multiplex PCR for mec A and fem B genes made the test both rapid and specific. Use of this strategy would enable rapid screening of nasal carriers and early implementation of hospital infection control measures. PMID- 27407360 TI - CORRELATIONSHIP OF CATHEPSIN D AND TOPOISOMERASE II ALPHA WITH NUCLEAR GRADING IN BREAST CANCERS. AB - 56 cases of infiltrating duct carcinoma of the breast were studied for the expression of cathepsin D and topoisomerase II alpha. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Cathepsin D posltivity in tumour cells and stromal cells was seen in 44.6% and 55.4% cases respectively, whereas topoisomerase II alpha positivity was seen in 33.9% cases. In grade II tumours cathepsin D in tumour cells and stromal cells was 44.4% and 47.2% respectively, as compared to 27.8% posltivity for topoisomerase II alpha. The corresponding figures for grade III tumours were 50.0%, 79.6% and 64.3 % respectively. As grade I comprised only 3 cases no statistical correlation could be observed. It is evident that with increase in tumour grade there is a statistical increase in expression of cathepsin D, a lysosomal acidle protease-implicated in the process of tumour invasion and metastasis, and of topoisomerase II alpha, a marker of rapid cell proliferation and aneuploidy. PMID- 27407361 TI - TRENDS AND ISSUES IN RELATION TO ALCOHOL DEPENDENCE IN THE ARMED FORCES. AB - Alcohol dependence syndrome has an estimated prevalence of 1533% of all psychiatric hospitalizations in a year. There is an increasing trend in incidence among JCOs/ORs. The index of admission was highest in Armoured Corps, Mechanized Infantry and Army Medical Corps (AMC). Generally a service personnel becomes dependent at 35 years of age after about 11 years of drinking. The average consumption of alcohol dependent individuals was 6-7 pegs/day. A family history of alcohol abuse/dependence was found in 31 % cases. Alcoholics had high anxiety, depression, extroversion, neuroticism and psychopathic deviate traits. Alcoholism was associated with significantly low self esteem. Significantly more alcoholics were alexithymic as compared to non-alcoholics. The gamma glutamyl transferase (GGT) and mean corpuscular volume (MCV) were found to be useful diagnostic aids for alcoholism. Almost a third of alcoholics have potentially serious physical problems, 20% suffer from various degrees of psychotic phenomena, 40-55% have significant marital, occupational and disciplinary problems, while 3-6.93% attempted deliberate self-harm. Despite wide variations in mode of disposal, after diagnosis only a small percentage of alcoholics remain in service beyond three years. There is need for concerted investigations into the precipitating and perpetuating factors, co-morbidity, the process of change towards betterment and the long-term outcome of alcoholism in service personnel. PMID- 27407362 TI - END OF LIFE CARE DECISIONS AND THE HOSPICE MOVEMENT. AB - Inspite of spectacular technological advances made in the recent years, modern medicine has not been able to deny the inevitability of death. Slowly but surely, the approach towards death is changing with increasing emphasis on various end of life care decisions. Many of these decisions are being actively discussed, debated and practised all over the world. Palliative care in hospice has become an accepted mode of management of terminally ill patients, for whom the prognosis is limited. Increase in life expectancy of the Indian people and a strong movement to authorise ex-servicemen for treatment of malignant and other chronic diseases in service hospitals, requires the Armed Forces to consider these end of life care decisions and plan for terminal care in hospice. PMID- 27407363 TI - LINEZOLID. PMID- 27407364 TI - ANGIOLYMPHOID HYPERPLASIA WITH EOSINOPHILIA: A CASE REPORT. PMID- 27407365 TI - CARDIAC INVOLVEMENT IN SNAKE BITE. PMID- 27407366 TI - KLIPPEL FEIL SYNDROME WITH PULMONARY CYST. PMID- 27407367 TI - BRONCHOESOPHAGEAL FISTULA AND DYNAMIC BRONCHOSCOPY. PMID- 27407368 TI - CONJOINED TWINS. PMID- 27407369 TI - EWING'S SARCOMA OF MANDIBLE - A RARE NEOPLASM. AB - Ewing's sarcoma is a highly malignant tumour seen in the age group of 5 to 25 years, primarily afflicts long bones of the extremities followed by pelvis, ribs and vertebrae. The involvement of this lesion in the mandible accounts for only 2% of the reported cases. Ewing's sarcoma particularly in children, poses difficulty in arriving at a diagnosis and could be established only by histopathological and electron microscopic examination. This is a radiosensitive lesion, however, surgery with chemotherapy is the preferred treatment of choice in mandible. A case of Ewing's sarcoma in a 7 year old female patient was managed by chemotherapy and aggressive surgical approach with gratifying results and no recurrence till date. PMID- 27407370 TI - RESECTION AND ENDOPROSTHETIC RECONSTRUCTION OF KNEE JOINT FOR OSTEOGENIC SARCOMA OF DISTAL FEMUR. PMID- 27407371 TI - A LARGE ASYMPTOMATIC DANDY WALKER CYST IN AN INFANTRY SOLDIER. PMID- 27407372 TI - INTRATHORACIC KIDNEY: A Case Report. PMID- 27407373 TI - A CASE OF BRAIN ABSCESS. PMID- 27407374 TI - FLUID AND ELECTROLYTE CONCEPTS IN NEW BORNS. PMID- 27407375 TI - High Incidence of Severe Parasitemia in Falciparum Malaria: REPLY. PMID- 27407376 TI - High Incidence of Severe Parasitemia in Falciparum Malaria. PMID- 27407377 TI - SEXUALLY TRANSMITTED DISEASES IN AND AROUND GUWAHATI (ASSAM). PMID- 27407378 TI - From the Editor's Desk. PMID- 27407379 TI - Wound Healing - A Surgical Fundamental Revisited. PMID- 27407380 TI - War Wounds - Changing Concepts. AB - The accepted standard treatment of war wounds through the last century has been debridement and delayed primary closure. However, recently, there has been a renewed Interest In primary closure of these wounds. 1481 war wounds were managed by the authors and out of 789 soft tissue injuries, 389 (47%) were closed primarily (group 1) after meticulous debridement and 220 (28%) underwent delayed primary closure (group 2). The infection rate in group 1 was 4.87% compared to 6.36% in group 2. The average hospital stay in group 1 was 15 days, significantly shorter by 10 days than in group 2. In the war zone both time and resources are at a premium and primary closure of selected wounds offers a better alternative to delayed primary closure. PMID- 27407381 TI - Renal Transplantation - Calcutta Experience. AB - 31 renal transplant procedures have been performed at this centre. Renal donors were father in 4, mother in 4, brother in 12, sister in 4, brother-in-law in 1 and wives in 6 cases. Median age of recipients and donors was 35.2 years (20-55) and 38.3 years (24-60) respectively. After a mean follow up of 15.7 months (2 40), graft survival was 96.7% and patient survival 90-3%. Three patients (9.6%) required surgical re-exploration, one each for, peri-graft haematoma, arterial kink and graft artery thrombosis. 6 patients (19.3%) required anti rejection therapy with resultant complete normalisation of graft functions. Medical complications noted were post transplant diabetes mellitus in 6 (19.3%), azathihoprine induced bone marrow suppression in 1(3.2%), tuberculosis in 2 (6.4%), post transplant erythrocytosis in 2 (6.4%) and recurrent urinary tract infection (UTI) in one (3.2%) patients. 3 patients (9.6%) died with functioning graft, one due to lung infection and the other due to haemorrahagic pancreatitis and third due to infective endocarditis. PMID- 27407382 TI - Role of Molecular Typing in Live Related Donor Renal Transplantation. AB - In renal transplantation, a good HLA-DR match is associated with higher success rate of graft outcome. It is particularly so In high risk recipients. Serological HLA-DR typing is not always easy due to a number of technical problems. In view of this, a comparison of serological and molecular typing was done in our institutions. A total of 64 live related donor patients of renal transplantation were studied. Serological typing was done by conventional methods. Molecular HLA class II typing was done by polymerase chain reaction (PCR) based sequence specific oligonucleotide probe (SSOP) hybridization technique. An overall discrepancy of 19.5% was observed in the DR typing obtained by serology and PCR SSOP of all the recipients and donors. 14.5% of cases showed discrepancy in the results of only one DR antigen. Serological typing failure was seen in 10.9% of total cases. In 19.5% cases, only one DR antigen was assigned by PCR-SSOP as compared to two antigens by serological methods. Maximum number of discrepancies were seen in DR 2 antigens. There was no appreciable difference of graft survival shown in the patients typed by both methods. However, higher incidence of acute graft rejection episodes were seen in patients with 1 antigen mismatch as compared to zero mismatch. It is concluded that HLA-DR typing should be carried out by molecular methods as these have been found to be more specific and accurate. PMID- 27407383 TI - Regional Block Anaesthesia - How Effective is it for Extremity Trauma? AB - Regional block anaesthesia (RBA) techniques are eclipsed by the widespread use of general anaesthesia (GA), especially in trauma surgery. This is despite the numerous advantages that regional blocks have to offer. We conducted a study to evaluate efficacy, safety and feasibility of RBA in isolated extremity trauma in war scenario. A prospective study was carried out over a period of eight months. There were a total of 96 patients with splinter, mine blast and gun shot wounds. Supraclavicular or axillary brachial block was employed for upper extremity surgery. 3 in 1 femoral block with classical sciatic block at hip or popliteal fossa was administered for lower limb operations. All patients were stabilized prior to the procedure. A combination of lignocaine 3 mg/kg of 2% and bupivacaine 1.5 mg/kg of 0-5% with dilution to make a volume of 0.75 ml/kg was employed. Assessment was made for onset, duration and degree of anaesthesia. Haemodynamic parameters and oxygen saturation were measured during the peritraumatic period. 92.5% cases had good motor and sensory anaesthesia and permitted unhindered surgery without supplementation. The rest required GA/dissociative anaesthesia (DA). Post operative pain relief lasted for an average of 4-5 hours. No patient had derangement of haemodynamic parameters or oxygen saturation. There was no systemic drug toxicity, local complications or mortality in our series. We found RBA for isolated extremity trauma to be simple, safe and effective with consistent results. PMID- 27407384 TI - A Study of Hostility, Career Choice and Job Satisfaction Among Surgeons. AB - The present study has been carried out to study the hostility pattern of surgeons and compare it with other specialities. 100 teachers working in different specialities in Post Graduate Institute of Medical Sciences (PGIMS) Rohtak (Surgery and allied specialties 21, Medical and allied specialities 14, Non clinical specialities 30) were given Hostility and Direction of Hostility Questionnaire (HDHQ) along with questions regarding their choice of career and Job satisfaction. Hostility pattern did not differ statistically among these groups. Surgeons showed strong aptitude for the field and were contended with their choice of speciality but their Job satisfaction was low. Possible explanations and implications of the study are discussed. PMID- 27407385 TI - The Malone Antegrade Continence Enema Procedure, An Indian Perspective. AB - Eight patients with bowel incontinence underwent an open Malone Antegrade Continence Enema (MACE) procedure between May 1997 to May 2000. Indications for the procedure included high anorectal malformation in 3, bowel dysmotility in 1. spinal dysraphism in 3 and presacral teratoma in 1. Age at presentation varied between 06 to 12 years. All but one patient claimed excellent results. Complications of the procedure included stomal stenosis in 1, stomal leak in 2 and inadequate emptying of effluent in 1. Patient selection was the key to success. All patients except one, were children who were literate and had access to a western toilet Whereas, for the vast majority in the Indian rural setting, the procedure may not be beneficial but for a select group of bowel incontinence children, this procedure may bring a dawn of hope. PMID- 27407386 TI - Is Catgut Really Obsolete? Experience with Buried Subcuticular Catgut Sutures in Operative Wounds. AB - A good scar after surgery is desirable. Skin closure with subcuticular sutures is known to give better scars. Absorbable sutures reduce suture track infection. Catgut is a monofilament absorbable suture, which has not been generally recommended for skin for fear of infection and dehiscence. Buried subcuticular sutures using catgut were given in 350 cases after surgery. Disorders known to impair wound healing were excluded. Infection and dehiscence was noted in only 4.3% cases. Dehiscence in the absence of wound infection was seen in only two cases (0.6%). Excellent healing with fine linear scars was the result in 92% patients. Catgut can be safely used for skin closure by the described technique of buried subcuticular sutures in clean surgical wounds with gratifying results. It has advantages over its synthetic counterparts of easy availability, economy and good handling. The fear of poor result with catgut as a skin suture is unfounded. PMID- 27407387 TI - Computerised Tomography Features in Gliomas. AB - 106 cases of intracranial tumours were evaluated, out of which 42 cases (39.6%) were histologically confirmed as gliomas. Computerised tomography (CT) imaging characteristics of glioma were studied with respect to morphology and contrast enhancement to find a possible correlation between CT appearance and the grade of malignancy. It was found that there is a range of patterns both before and after intravenous contrast, which allows an assessment of grading of the tumour with a fair degree of reliability. PMID- 27407388 TI - Resistant Malaria : Current Concepts and Therapeutic Strategies. PMID- 27407389 TI - Common Medicolegal Problems Faced by Medical Officers of Armed Forces Medical Services. AB - Many a times medical officers of Armed Forces Medical Services face problems concerning policy as well as policy matters la connection with their medico-legal duties and responsibilities. This is particularly so with hospital administrators, pathologists and surgeons. Over and above, the lack of Army Orders and DG Memoranda on this topic makes one feel at a loss. The consequences of mistakes committed while performing medicolegal duties may include strictures from the courts. This article tries to list the common medicolegal problems encountered by medical officers of Armed Forces Medical Services working at different levels and in different capacities, and provides solutions for the same. PMID- 27407390 TI - Equipment Review. PMID- 27407392 TI - Clinical Features And Management Of Snake Bite. PMID- 27407391 TI - Anti-leukotrienes in Childhood Asthma. AB - Bronchial asthma is an inflammatory condition. The inflammatory actions of leukotrienes (LT) B4, C4, D4, and E4 have been shown experimentally to play a role in inflammatory mechanisms, producing asthma. Antileukotrienes (ALT) or leukotrienes antagonists (LA) is a new class of anti-asthma drugs with anti inflammatory role. LT modifiers from the groups of 5 lipoxygenase inhibitor and Cys LT1 receptor antagonists, are found useful in asthma therapy. LAs are of main use in young infants and toddler with recurrent wheezing, children with moderate to severe chronic asthma on steroid therapy and in allergic rhinitis. In chronic asthma they are required to be used for prolonged periods with other anti-asthma agents. Except for Montelukast and Zafirlukast, which can be used in children above two and six years of age respectively, the paediatric use of other agents is yet to be established. However, these agents are essentially safe. The cost of LAs is reasonably high. At present, with available evidence, these drugs are considered promising in management of asthma in children. However, there is need to do more long term clinical trials for ascertaining their effectivity in different types of asthma to compare their effects with long acting B2 agnoists and chromones, so as to optimally explore their utility. PMID- 27407393 TI - Multicentric Castleman's Disease. PMID- 27407394 TI - Melanotic Neuroectodermal Tumour of Infancy. PMID- 27407396 TI - Reduction Mammaplasty Using McKissock Vertical Bipedicle Technique. PMID- 27407395 TI - Unusual Presentation of Fracture Scapula. PMID- 27407397 TI - Retroperitoneal Teratoma in an Adult With Carcinoid as the Main Component. PMID- 27407398 TI - Ischaemic Bowel Disease : A Case Report. PMID- 27407399 TI - Treacher Collins Syndrome : A Report on Two Cases. PMID- 27407400 TI - Mesenchymal Hamartoma of Liver : A Case Report. PMID- 27407401 TI - Dissecting Aortic Aneurysm Presenting as Superior Vena Cava Syndrome. PMID- 27407402 TI - Spinal Anaesthesia for Exploratory Laparotomy in a Six Day Old Neonate : A Case Report. PMID- 27407403 TI - TECHNOLOGY UPDATE - PINLESS FIXATOR: REPLY. PMID- 27407404 TI - TIP OF THE ISSUE. PMID- 27407405 TI - TECHNOLOGY UPDATE - PINLESS FIXATOR. PMID- 27407406 TI - REGIONAL BLOCKS IN EXTREMITY TRAUMA. PMID- 27407407 TI - MEHTAS LIGATURE FORCEPS FOR TONSILLECTOMY. PMID- 27407408 TI - REGIONAL BLOCKS IN EXTREMITY TRAUMA: REPLY. PMID- 27407409 TI - HOSPITAL BEDS IN THE ARMED FORCES: REPLY. PMID- 27407410 TI - HOSPITAL BEDS IN THE ARMED FORCES. PMID- 27407411 TI - PREOPERATIVE BLEEDING TIME AND CLOTTING TIME TESTS :USEFUL OR WASTEFUL? PMID- 27407412 TI - RADICAL CURE OF VIVAX MALARIA : 5 OR 14 DAYS. PMID- 27407413 TI - Foreword. PMID- 27407414 TI - Doctor's Dilemma. PMID- 27407415 TI - Hysteroscopy: Past, Present and Future. PMID- 27407416 TI - Office Hysteroscopy: An Insight. AB - In clinical gynaecology, one comes across a large number of patients with intra uterine pathology. Various investigations have been devised to evaluate these disorders. Hysteroscopy, since its advent has progressed a long way to be recognized as the gold standard in diagnosing intra-uterine pathologies. An attempt to make it an OPD procedure was encouraging. 100 cases of office hysteroscopy were performed at our centre. Pain, patient comfort and acceptability were studied. A favourable outcome was achieved and wider application is recommended. PMID- 27407417 TI - A Study of Breast Feeding Practices Among Families of Armed Forces Personnel in a Large Cantonment. AB - A cross sectional epidemiological study design was undertaken on a randomly selected sample of 175 families of Armed Forces personnel staying in a large cantonment and having at least one child in the age group 3 to 24 months. The mean duration of lactational amenorrhoea was found to be 6.24 months (SD +/- 3.25 months) and that of breast feeding was found to be 11.14 months (SD +/- 6.37 month). The present study observed positive association between the duration of exclusive breast feeding and the duration of lactational amenorrhoea, as well as between the lack of practice of exclusive breast feeding and number of spells of upper respiratory tract infection and acute gastroenteritis. Based on the findings of the study, certain measures to promote the practice of exclusive breast feeding for the first 4-6 months of life have been suggested. PMID- 27407418 TI - Cohort Study on the Recurrence Rate of High Altitude Pulmonary Oedema. AB - Keeping in view the importance of High Altitude Pulmonary Oedema (HAPO) as well as the absence of published evidence as regards recurrence rate of this disease, a cohort study was undertaken, based on data available with the Central Diseases Registry. The inception cohort consisted of all cases of HAPO occurring over a one year period, This cohort was followed up for another 12 months, to observe any recurrence. The study revealed that the recurrence rate of HAPO in terms of Incidence density was 1.83 per 1000 person-months of those who had an initial episode (95% confidence limit 0.53 to 3.13 per 1000 person-months). The cumulative incidence was 32.9 per 1000, over an average follow up of 18 months (95% confidence limit 4.55 to 61.25 per 1000). The time gap between the initial episode and recurrence was 115 to 208 days. All recurrent cases had their initial as well as recurrent episode at the first stage of high altitude (9000 to 12000 feet), with the onset being within 48 hours of entry into high altitude. Based on the findings, some recommendations for prevention of recurrence of HAPO have been submitted. PMID- 27407419 TI - Serum Zinc Levels in Cutaneous Disorders. AB - Serum zinc levels were studied in 75 patients of different cutaneous disorders and 24 healthy controls. It was found to be significantly lower in acne vulgaris (71.5 +/- 21.5ugm/100ml), leprosy(85.9 +/- 26.9ugm/100ml) and psoriasis (93.3 +/- 25.9ugm/100ml) as compared to healthy controls (105.3 +/- 30.1ugm/100ml). No significant correlation was found in other cutaneous disorders studied i.e. vitiligo and aphthous ulcers where serum zinc levels were found to be 97.3 +/- 26.6 ugm/100ml and 105.2 +/- 23.5 ugm/100ml respectively. PMID- 27407420 TI - Role of Ambulatory Blood Pressure Measurement in Diagnosis and Control of Hypertension. AB - Office blood pressure (BP) measurements by sphygmomanometer are not necessarily representative of patient's usual blood pressure. In contrast, ambulatory blood pressure measurements (ABPM) represent a large number of readings and may reflect the actual BP status of an individual. In this study, 150 individuals were studied in 2 groups. 110 patients (group A) had stage I & II, hypertension based on casual BP readings. 26 (23.6%) of them were found to be normontensive as per existing ABPM standard. There were 40 patients with poorly controlled hypertension on multiple drugs (group B). The trough/peak ratio of > 50% was seen in 12.5% of these patients at start of study. This increased to 84.8% after modification of drugs as per the profile on ABPM, thus indicating usefulness in achieving a smoother control. PMID- 27407421 TI - Evaluation of Muscle Strength Among Different Sports Disciplines: Relevance for Improving Sports Performance. AB - A pilot cross-sectional study among 262 service sportsmen belonging to different sports disciplines was carried out to evaluate various indicators of muscle strength, such as peak torque, peak torque to weight, time to peak torque, maximum power, explosive work etc., using isokinetic testing during flexion and extension of the knee joint in sitting positions at different angles. It was found that peak torque varied significantly among the various sports disciplines depending on the requirement of each sports discipline (p < 0.01). The relevance, advantages and limitations of the tests to enhance sports performance have been discussed. However, discussion has been restricted to review of western literature on the subject as no Indian studies in the field were available for comparison. PMID- 27407422 TI - Serum Ornithine Carbamoyl Transferase as a Surrogate Marker in Malaria. AB - Ornithine carbamoyl transferase (OCT) activity and other liver function tests were studied in a total of 50 patients of clinical malaria and 15 controls. They were grouped as group I (positive for malarial parasite on peripheral blood smear, n=18), group II (negative for malarial parasite on peripheral blood smear (PBS) but responded to antimalarials, n=17) and group III (peripheral blood smear negative and did not respond to antimalarial therapy, n=15). The mean OCT levels were significantly raised in group I (6.79 +/- 1.84 IU/L, p value = 0.006) and group II (5.0 +/- 1.15 IU/L, p value = 0.014) as compared to controls (2.5 +/- 1.13 IU/L) and returned to normal after treatment In contrast, group III had normal levels except in a case of kala azar and septicemia where OCT levels were high and increased further on treatment. Taking PBS positivity as a gold standard of diagnostic criteria, OCT had a sensitivity of 83% and specificity of 86% with a high positive predictive value of 88% as compared to ALT which had a lower sensitivity of 55% and specificity of 80%. The clinical response rate in PBS negative cases of fever having high OCT level was 83% as compared to 35% in cases with normal OCT level, making OCT a good surrogate marker of malaria. OCT levels could also be of prognostic significance as 2 cases of cerebral malaria had high OCT levels of 11.1 UAL and 10.7 IU/L, respectively. PMID- 27407423 TI - Evaluation of Cases of Secondary Infertility by Hysterosalpingography and Hysteroscopy. AB - Hysterosalpingography (HSG) and hysteroscopy, two investigative modalities were performed on a group of 50 patients of secondary infertility and the results analysed. In this study, the infertile women were evaluated with HSG followed by hysteroscopy to evaluate the causes of secondary infertility and attempt a correlation between these investigative modalities. The complete agreement between HSG and hysteroscopy was established in 43 (86%) cases. HSG showed a false positive rate of 23% and false negative rate of 6%. The sensitivity of HSG was 77% and specificity 93% in diagnosing uterine conditions. The conditions missed were likely due to the overfilling of the uterus. HSG showed a good correlation with hysteroscopy and being a safe and simple procedure, it should be the preliminary Investigation in infertile patients. Thus, the two investigative modalities were found to be complementary to each other rather than being mutually exclusive. PMID- 27407424 TI - Bioterrorism: An Emerging Public Health Problem. PMID- 27407425 TI - Complications of Hysteroscopic Surgery. PMID- 27407426 TI - Clinical Features and Management of Blast Injuries. PMID- 27407427 TI - Is it Hydranencephaly - A Variant? PMID- 27407428 TI - Cleft Palate Rehabilitation: A Combined Orthodontic Surgical and Prosthodontic Approach. PMID- 27407429 TI - Van Wyk and Grumbach Syndrome (A Syndrome of Incomplete Isosexual Precocity and Juvenile Hypothyroidism). PMID- 27407430 TI - Eccrine Cylindroma of Lip. PMID- 27407431 TI - Adamantinoma of Tibia. PMID- 27407432 TI - Abdominal Tuberculosis - An Enigma. PMID- 27407433 TI - Sjogren - Larsson Syndrome. PMID- 27407434 TI - Rectus Sheath Haematoma. PMID- 27407435 TI - Audit of Blood Requisition: Reply. PMID- 27407436 TI - Audit of Blood Requisition. PMID- 27407437 TI - Stents in Acute Non-Q Wave Myocardial Infarction. PMID- 27407438 TI - Reply: Stents in Non Q Wave Myocardial Infraction. PMID- 27407439 TI - Say No to MMR; Epidemiological Reasons: A Rebuttal. PMID- 27407440 TI - Say Yes to MMR: Ethical, Scientific and Practical Reasons. PMID- 27407441 TI - Reply: Say Yes and No to MMR; 'Theory of Relativity'!! PMID- 27407442 TI - Advanced Trauma Life Support System (ATLS) in a Peripheral Hospital. PMID- 27407443 TI - For Whom Do We Toil? PMID- 27407444 TI - For Whom Do We Toil?: Reply. PMID- 27407445 TI - Multi-drug Regimen in Leprosy and its impact on Prevalence of the Disease. PMID- 27407446 TI - Malaria Control: Current Concepts. PMID- 27407447 TI - Community Based Study of AIDS Awareness and Attitudes among School and College going Teenagers from Rural Background. AB - A community based, cross-sectional, analytical study was undertaken among children aged 13 to 19 years, who were currently studying in high school, intermediate or graduate classes, in a rural area of Maharashtra. A sample of 151 girls and 162 boys formed the material for this study. Data was collected by well qualified, centrally trained interviewers, using a pre-tested instrument, administered by personal interview technique. The study indicated that the general awareness about AIDS was very high, with more than 90% of the respondents having heard of AIDS and also identifying it as an important health problem in our country. However, less than 50% knew correctly about the etiology of AIDS, or the difference between HIV and AIDS. Similarly, a very high proportion of the subjects knew about the modes of transmission, though a much lesser proportion had the knowledge about the role of improperly sterilised syringes and needles. Similarly, a general lack of awareness about other sexually transmitted diseases was noticed. Lacunae in knowledge also existed as regards knowledge about high risk groups, like commercial sex workers (CSWs), intravenous drug users (IVDUs), truck drivers and professional blood donors. A very large majority of the subjects had a very positive and healthy attitude about sex, and did not accept pre or extra marital sex, as well as, were desirous of obtaining AIDS education as a part of school / college curriculum. Based on the findings of the study, certain recommendations on AIDS education in the reference population have been submitted. PMID- 27407449 TI - Biliary Lithiasis: Prevalence and Ultrasound Profile in a Service Hospital. AB - Real time gray scale ultrasonography of upper abdomen was carried out in 1237 cases for varied indications. Overall prevalence of biliary lithiasis was 11.56% with female to male ratio of 4:1. Fifty years and below, female to male ratio was 6.5:1. 88.8% cases of biliary lithiasis were 60 years and below. Gall bladder dyspepsia (61.5%) and right upper quadrant pain (41%) were the main presenting features of biliary lithiasis. 26 patients (18%) presented with acute abdomen. Asymptomatic gallstones were found in 25 (17.5%) cases. Solitary calculus was less common than multiple calculi with a ratio of 1:4. Amongst cases of multiple calculi the small sized (2-4 mm) variety was the maximum (49%) followed by medium sized (5-10mm) and large sized (>10mm) calculi respectively. PMID- 27407448 TI - Study of the Impact of Deltamethrin Impregnated Mosquito Nets on Malaria Incidence at a Military Station. AB - Deltamethrin impregnated mosquito nets have been successfully used all over the world to combat malaria. To study the efficacy of these mosquito nets in the service conditions of Armed Forces, a field trial of Deltamethrin impregnated mosquito nets was carried out at Military Stations 'A' (trial station) and B (control station) between July 96 to June 99. July 96-June 97 was the pretrial year during which base line data was collected for malaria incidence. Three rounds of Deltamethrin impregnation of the mosquito nets were done in the trial station for the actual trial duration (July 97-June 99) in lieu of residual spraying. Antimalaria measures including residual spray were continued as usual in the control station. The intervention led to a significant decline in slide positivity rate and malaria incidence in the trial station. Malaria cases declined by 87% in the trial station whereas the control station noticed an increase by 75% at the end of the trial. PMID- 27407450 TI - Community Dentistry in Armed Forces. AB - The objectives of community dentistry are to motivate the public to change their behaviour and planning for prevention and control of dental diseases. Oral health of army personnel is recognized as equally important in relation to general health. In the present study, the army personnel were inspected comprehensively utilizing the latest WHO survey proforma 1997 to know the pattern of oral diseases, prevalence of deleterious oral habits and treatment needs. The aim of this epidemiological study was to assess the oral health status and treatment needs of army personnel. PMID- 27407451 TI - Aggressiveness - The key to a Successful Outcome in Necrotizing Soft Tissue Infection. AB - 16 patients with necrotizing soft tissue infections were managed during last three years in various service hospitals. The experience indicates that there is considerable overlap in clinical findings and bacteriology. The infections seem to be variations of the same disease process, a spreading necrotizing infection. The number of these patients suggests that there is an increasing incidence of this entity. Staphylococcus and coliforms were the commonest organisms cultured in most of these patients. Because of the high mortality rate upto 50% as reported, we advocate aggressive and early treatment of this condition. Urgent radical exploration, excision of all necrotic tissue and adequate drainage of the deep fascial planes was done in all patients until healthy tissue planes were reached. A strong index of suspicion aids early diagnosis which ensures a favourable outcome. Our study indicates that the lower gastrointestinal tract should be considered as a possible cause of infection in all patients with synergistic gangrene. The involvement of the perineum and scrotum was most common. All these patients were treated with a common approach of resuscitation, broad spectrum antibiotics, immediate surgical excision of all necrotic tissue, aggressive nutritional therapy and early skin coverage with 20% mortality. The infection was primary in 8, postsurgical in 4 and following trauma in 4 cases. In majority of patients, Staphylococcus with beta haemolytic streptococci and E coli were the organisms isolated initially. Mortality was highest in intensive infections extending the abdomen and chest. Aggressive, effective and early treatment of necrotizing soft tissue infections is imperative to prevent a fatal outcome. Urgent radical exploration by the most experienced surgeon available is essential and includes wide excision of all necrotic tissue and adequate drainage of the deep fascial planes until indubitably healthy tissue is experienced. The surgeon must be prepared to proceed to a laparotomy, diverting colostomy or a suprapubic cystotomy where there exists any element of doubt. Aggression is also of significance in resuscitation, early institution of empirical broad spectrum antibiotic therapy, elaborate repeated daily dressings with hydrogen peroxide and to allow further debridement till the process is controlled. PMID- 27407453 TI - Fertility Enhancing Hysteroscopic Surgery: Our Experience. AB - 690 hysteroscopies done over a period of four and a half years for infertility were evaluated. 85 therapeutic hysteroscopic procedures like hysterscopic metroplasty, lysis of intrauterine adhesions, electroresection of fibroids, removal of foreign bodies and cornual cannulation were carried out. These minimally invasive procedures were associated with satisfying results, least morbidity, shorter hospital stay and high patient satisfaction. PMID- 27407452 TI - Random Amplification of Polymorphic DNA Based Typing of Pseudomonas Aeruginosa. AB - Pseudomonas aeruginosa was isolated from various sources during the course of an epidemic outbreak of bacterial endophthalmitis following an eye camp at Sangli, Maharashtra. 15 distinct isolates were obtained from clinical samples. Typing of the 15 isolates was performed by random amplified polymorphic DNA (RAPD) analysis, pyocin typing and antibiogram. RAPD typing was rapid, labour friendly and could be done within six hours. RAPD analysis produced reproducible electrophoretic band patterns on the basis of which three distinct amplification patterns could be visualised. The conventional typing methods were labour intensive and took about 48 hours. However, the results of RAPD typing, pyocin typing and antibiogram did not correlate with each other. This study suggests that RAPD typing could be an additional rapid typing method for studying the epidemiology of infectious disease outbreaks due to P aeruginosa. PMID- 27407454 TI - Lipid Profile In Transplant Patients: A Clinical Study. AB - 15 renal transplant recipients were studied for their lipid profile. The patients were on regular post transplant follow up and had non clinical or laboratory evidence of graft dysfunction, intercurrent infection or post transplant diabetes mellitus for at least 3 months prior to the study. The mean duration of transplant was 15 +/- 9.5 months (range 3-32 months). Majority (86%) were on triple immunosuppression therapy and received a mean prednisolone dose of 10.5 mg. An equal number of healthy subjects were randomly selected and studied for their lipid profile and served as control for the study group. There was no significant change in the HDL-cholesterol level as compared with controls. However, these patients showed a significantly higher LDL-cholesterol and total cholesterol levels. Further, a significant inverse correlation was observed between triglycerides and total cholesterol levels and transplant duration. PMID- 27407455 TI - A Two Year Experience in Continuous Positive Airway Pressure Ventilation Using Nasal Prongs and Pulse Oximetry. AB - In a prospective study 26 of the 116 consecutive neonates suffering from respiratory distress survived on varying concentrations of humidified oxygen. Continuous positive airway pressure (CPAP) of 4-12 cm of water was applied through short nasal prongs to 90 neonates. Haemoglobin oxygen saturation (SaO2) rose in all and it was maintained steadily above 85% in 46 (51%) infants who survived. The mean duration of CPAP among the survivors was 61 hours (range 8-190 hours). Common indications of CPAP ventilation were hyaline membrane disease (HMD) (27.7%), meconium aspiration syndrome (MAS) (20%), apnea of prematurity (18.8%) and asphyxia (17.7%). Neonates weighing >1000 gm faired well with overall survival of 60 to 82.35%. However, among the 16 babies weighing <1000 gm, only 3 (18.75%) survived. 4 infants on CPAP died due to pneumothorax, none had complications of oxygen toxicity. The 44 CPAP failures, fared poorly even when shifted to intermittent positive pressure ventilation (IPPV) regardless of their weight and 1 among the 5 survivors developed grade 1 intraventricular haemorrhage. It was concluded that nasal CPAP ventilation with pulse oximetry is a simple and efficient method of treating respiratory distress in newborns. This technique can be adopted even by smaller hospitals where the equipment and expertise for IPPV and arterial blood gas (ABG) monitoring are not feasible. PMID- 27407456 TI - Innovation: The Simple Stretchers. PMID- 27407457 TI - Artifical Blood. AB - Elimination of unwanted side-effects, especially transfusion-transmitted diseases (HIV and hepatitis) and leucocyte-mediated allosensitisation, is an important goal of modern transfusion medicine. The problems and high cost factor involved in collecting and storing human blood and the pending world-wide shortages are the other driving forces contributing towards the development of blood substitutes. Two major areas of research in this endeavour are haemoglobin-based oxygen carriers (HBOCs) and perfluorochemicals. Even though they do not qualify as perfect red blood cell substitutes, these 'oxygen carrying solutions' have many potential clinical and non clinical usages. These can reach tissues more easily than normal red cells and can deliver oxygen directly. These are not without adverse effects, and extensive clinical trials are being conducted to test their safety and efficacy. New understandings on the mode of action of these products will help to define their utility and application. Only after successful clinical trials can they be used for patient management, after approval by the FDA. PMID- 27407458 TI - Technique of Blood Pressure Measurement. PMID- 27407459 TI - Anaphylactic Reaction: An Overview. PMID- 27407460 TI - Radiological Quiz. PMID- 27407461 TI - An Unusual Herniation Through Omentoplasty Defect. PMID- 27407462 TI - Neglected Posterior Dislocation of Shoulder. PMID- 27407463 TI - Trichotillomania. PMID- 27407464 TI - Ramsay Hunt Syndrome Treated with Oral Acyclovir. PMID- 27407465 TI - Paget's Disease of the Bone. PMID- 27407466 TI - Retroperitoneal Cyst. PMID- 27407467 TI - Shoulder Dystocia. PMID- 27407469 TI - Maternal Haemoglobin and Birth Weight. PMID- 27407468 TI - Goodpasture's Syndrome. PMID- 27407470 TI - Maternal Haemoglobin and Birth Weight: Reply: A Correlative study of Maternal Haemoglobin and Birth Weight. PMID- 27407471 TI - Military Environment nad Fecundity: A Study of Women in Uniform. PMID- 27407472 TI - Aerosol Antisepsis. PMID- 27407473 TI - Military Environment nad Fecundity: A Study of Women in Uniform. PMID- 27407475 TI - NICU Environment : Can we be Ignorant? PMID- 27407474 TI - New Therapies for Rheumatoid Arthritis. PMID- 27407476 TI - Evolving Medical Strategies for Low Intensity Conflicts - A Necessity. AB - Military medicine is the development within the art and science which is designed to carry out a specialized, essential and a highly significant mission under the adverse conditions of war. Low Intensity Conflict (LIC) is a mode of warfare which has come to stay and the Indian Military has to confront it as such. It is a campaign of nerves, less military and more psychological, with soldiers inevitably fighting with hands behind their back. The dichotomy the soldier faces, results in high levels of frustration leading to various stress disorders. The key in casualty survival lies in correct and timely psychological first-aid for which every section and platoon commander should be trained. Post Trauma Stress Disorder caused as a result of traumatic experience can deplete unit's efficiency and therefore needs monitoring for early detection and treatment. Evolving medical strategies for Low Intensity Conflict Operations (LICO), therefore assumes significance. PMID- 27407477 TI - Analgesic Effect of Oral Glucose in Neonates. AB - The International Association for the Study of Pain, has defined pain as "an unpleasant sensory and emotional experience connected with actual or potential tissue damage or described in terms of such damage". It was thought that the newborn baby does not experience pain because of incompletely developed nervous system. However, it has been shown that neurological system known to be associated with pain transmission and modulation, is intact and functional. A study was conducted in our center to study the analgesic effect of administration of oral glucose in various concentrations, in neonates undergoing heel punctures, for collection of blood for investigations. This was compared with the analgesic effects of breast milk (which contains lactose). 125 full term normal neonates with no history of birth asphyxia or underlying neurological abnormality, requiring heel punctures for collection of blood for various investigations were selected for the study. They were matched for gestational age, birth weight and sex distribution and divided into 5 groups of 25 each. One group comprised control subjects and was administered sterile water. 3 groups were administered 1 ml of varying strengths of glucose solutions i.e. 10%, 25% and 50% respectively. The last group was given 1 ml of expressed breast milk (EBM). Prior to heel pricks, state of arousal, baseline heart rate (HR) and transcutaneous oxygen saturation (SpO2) were recorded by pulse oximeter in each neonate. Autolet, a mechanical device for capillary sampling, was used for heel pricks to give equal strength of painful stimulus in each procedure. Audio tape recorder was used to record the cry. The oral solution was administered slowly over 30 seconds by means of a syringe placed in the mouth. Heel puncture was done after 2 minutes, taking all aseptic precautions. HR and SpO2 were monitored using pulse oximeter. Pain response was assessed, by recording duration of crying, change in HR, change in SpO2 and facial action score after the procedure. Mean duration of cry and total cry over 5 minutes was significantly less in groups given 25% and 50% glucose solutions as compared to the control group and babies given EBM. Difference in mean increase in HR, fall in SpO2 were statistically significant between control group, EBM group and neonates given 25% and 50% glucose solutions respectively. Compared to control group, all other administered solutions (10%, 25%, 50% glucose and EBM) were found to reduce physiological and behavioral responses in neonates undergoing heel punctures. 25% and 50% glucose solutions were found to have maximal analgesic effect and both were found to be equally effective. EBM and 10% glucose solution have an equal analgesic effect but less than 25% or 50% glucose. This simple, cheap and safe method of oral analgesia can be easily used in neonates undergoing heel prick procedures during routine neonatal care. PMID- 27407478 TI - Potency Titration of Oral Polio Vaccine by Estimation of Live Virus Content Using Tissue Culture Technique. AB - Representative vaccines from 34 different batches of oral log10 (6.425) and a minimum titre of polio vaccine (OPV) were tested for potency by tissue culture technique. All 34 samples were found to be potent, a maximum titre of log10 (6.425) and a minimum titre of log10 (5.86) was obtained. In addition, 6 vaccines from the immunisation clinic (left over sample after immunisation) were also subjected to potency titration and their potency was found to be within normal limits. Adequate potency confirmed ideal storage condition of the vaccines in Armed Forces set up. PMID- 27407479 TI - Recent Trends in Dealing with Inguinal Hernial Sac. AB - High ligation of the hernial sac is a hallowed and time-honoured concept in inguinal hernia repair and it is considered essential for preventing recurrence. However, this concept has been contested in recent reports. We conducted a prospective study of 186 cases of inguinal hernia repair. In 92 cases the sac was ligated at the neck and excised, in 94 cases the sac was not ligated at all but either simply inverted or excised without ligation. The type of repair was Bassini's repair, Shouldice repair or Lichtenstein's repair. Degree of post operative pain was significantly less in those cases where sac was not ligated. There were no cases of recurrence in either group at 3 years follow up. Ligation of sac in inguinal hernia surgery is not only unnecessary and time consuming but also leads to increased post-operation pain. Recurrence is unaffected by not ligating the sac. PMID- 27407480 TI - Radiological Quiz. PMID- 27407481 TI - Field Trial of Relative Efficacy of Abate and Bacillus thuringiensis Against Simulium himalayense Larvae (Diptera simulidae). AB - Simulium himalayense (Diptera simulidae) are known pests which cause severe biting nuisance in North-East region and breed in its fast flowing rivers and rivulets. A field trial was undertaken to control this nuisance with the help of larvicides and to help ascertain relative efficacy of Abate and B thuringiensis against Simulidae. Abate proved to be an effective larvicide for river treatment wherein 0.1 PPM resulted in 100% larval reduction while in small streams, the treatment with Teknar (Bacillus thuringiensis) with 10 PPM for 10 minutes resulted in 80% larval reduction. The results of the present study showed that Abate was more effective in rivers while B thuringiensis proved to be useful in controlling the breeding in the rivulets. An integrated approach using chemical and biological agents is recommended and considered ecologically sound as it does not affect the fish and potability of water. PMID- 27407482 TI - Clinico-mycological Profile of Superficial Mycosis in a Hospital in North-East India. AB - A clinico-mycological study of superficial mycoses was conducted on 121 cases (98 males and 23 females). Direct microscopy by KOH mount and culture was undertaken to isolate the fungal pathogen in each case. The commonest age group involved was 21-30 years (39.6%). Dermatophytosis was the commonest clinical presentation (70.5%), followed by candidiasis (20.5%) and Pityriasis versicolor (9.0%). The commonest dermatophytosis was Tinea pedis (29.2%), followed by T cruris (26.2%). The commonest dermatophyte isolated was Trichophyton tonsurans (20.5%), followed by T rubrum (8.7%). Cultures grew a high proportion of non dermatophyte moulds (34%), of which Cladosporium spp (37.1%) was the commonest mould isolated. Total KOH positivity rate was 53.3% and total culture positivity rate was 79.1%. Our study revealed a variant local dermatophyte flora, a clinical pattern typical to our work environment in the Defence Services and a high isolation of yeasts and NDM. PMID- 27407483 TI - Surveillance of Scrub Typhus in the fringe areas around Pune : Potential for Transmission does exist. AB - A field based epidemiological study was undertaken to assess the potential of transmission of scrub typhus in the sylvatic and transitional (fringe) areas at ten different locations around Pune. Parameters studied included rodent trapping and identification, entomological parameters, immunological studies on rodent sera, and rodent organ impression smears. The study revealed that Rattus r rufescence, Rattus meltada, Suncus murinus and Rattus blanfordi were the predominant sylvatic rodent species. All the species showed mild to moderate infestation with trombiculid mite larvae, with Rr rufescence and S murinus showing even higher levels of infestation. Pooled rodent sera showed mild rise of OX2 in 13.9%, OX19 in 5.6% and OXK in 9.8% of the pooled sera. The rise in titres was appreciable among rodents from Lonavala, Khadakvasla, Panchet, Singhgadh and Kondhwa areas. Based on the findings of the study, certain recommendations on prevention, surveillance and epidemic investigations of scrub typhus in the Armed Forces have been submitted. PMID- 27407484 TI - Sinugenic Headache and Nasal Endoscopy. AB - This paper presents an evaluation and results of a study conducted on 62 patients out of 140 cases of chronic headache seen in ENT OPD. 32 patients were taken up for minimal endoscopic surgery. 23 cases (72%) have shown significant relief from headache over a period of 6 months or more. 11 cases showed anatomical / pathological variations at the ethmoidalis infundibulum, the commonest cause being enlarged bulla ethmoidalis followed by minimal polyps/polypoidal mucosa at the frontal recess area. Other causes are hyperplastic sinusitis, high posterior septal deviation, large middle turbinate, paradoxical middle turbinate and concha bullosa. PMID- 27407485 TI - Polyacrylamide Gel Affinity Electrophoresis for Separation of Enzyme Isoforms. AB - Affinity electrophoresis of differently glycosylated isoforms of enzymes using lectin as affinity ligand has been reported on support media such as cellulose acetate membrane (CAM) or agarose gel. We report a method for affinity electrophoresis in polyacrylamide gel (PAG) using wheat germ agglutinin (WGA). WGA is added to acrylamide-Bis mixture and incubated for 10 minutes at room temperature. This causes WGA to react covalently with acrylamide and Bis. Polymerization is initiated with addition of N,N,N,N-tetramethylethylene diamine (TEMED) and ammonium persulphate to give polyacrylamide gel with immobilized lectin. This gel has been found to effectively separate differently glycosylated isoforms of alkaline phosphatase (ALP). Concanavalin - A, similarly immobilized, did not give effective separation of ALP isoforms. The immobilization of lectin on polyacrylamide as support media requires less amount of lectin in comparison to CAM and agarose. Additional advantage of affinity electrophoresis on PAG is separation of biomolecules according to size. PMID- 27407486 TI - ECG Quiz. PMID- 27407487 TI - Current Trends in the Management of Typhoid Fever. PMID- 27407488 TI - Intracoronary Radiation. AB - With in-stent restenosis remaining major limitation of coronary stenting and adjunctive pharmacologic therapy and re-stenting having failed to reduce the rates of in-stent restenosis, a new treatment alternative is warranted. Vascular brachytherapy - the intracoronary delivery of radiation has been proposed as one such therapy. Thus far it is an important break-through in combating re-stenosis. Todate, 5 years of clinical data has been generated and further studies are underway to perfect the technology. PMID- 27407490 TI - Improved Device for CO2 Absorption in the One-Man Bag for High Altitude Pulmonary Oedema. PMID- 27407489 TI - Heat Stroke. PMID- 27407491 TI - Evidence Based Neonatology : What is New? (Cochrane Reviews Scan). PMID- 27407492 TI - Chiari Malformation Presenting as Cerebellar Degeneration. PMID- 27407493 TI - Management of Hypothermia with Warm Peritoneal Dialysis. PMID- 27407494 TI - Congenital Absence of Gall Bladder. PMID- 27407495 TI - Hip and Knee Dislocation in the Same Patient : A Case Report. PMID- 27407496 TI - Spontaneous Resolution of Cerebral Arteriovenous Malformation. PMID- 27407497 TI - Pregnancy in an Intravenous Drug User - Problem of Obstetric Management. PMID- 27407498 TI - Rounded Atelectasis - A Case Report. PMID- 27407499 TI - Vertebro-basilar Dolichoectasia with Fusiform Aneurysm : Evaluation by CT Angiography. PMID- 27407500 TI - Malignant Meningioma - Clinicopathological Study of an Unusual Presentation of a Rare Malignancy. PMID- 27407501 TI - Primary Hydatid Cyst of the Spleen. PMID- 27407502 TI - Psychiatric Manifestations in three cases of Acute Intermittent Porphyria. PMID- 27407503 TI - Active Childhood for Healthy Adulthood. PMID- 27407504 TI - Health Survey of Women. PMID- 27407505 TI - Common Medico Legal Problem. PMID- 27407506 TI - Common Medico Legal Problem: Reply. PMID- 27407507 TI - Medico-legal Problems. PMID- 27407508 TI - Medico-legal Problems: Reply. PMID- 27407509 TI - FIRE! PMID- 27407510 TI - Advances in Molecular Diagnosis of Tuberculosis. PMID- 27407511 TI - Film-less Radiology - A Future Perspective. PMID- 27407512 TI - Cryptococcal Meningitis: A Clinicopathological Account of Seven Cases Encountered in a Military Setting. AB - The clinicopathological profile of 7 cases of Cryptococcal meningitis encountered over one year period in a military hospital has been described. Severe persistent headache was the main form of presentation followed by features of progressive ill-health. Age range of cases was 34-55 years (mean 40.8 years). All were males and 6 were serving soldiers. Duration of symptoms ranged from 10 days to 6 weeks. Six patients were positive for HIV-1 antibodies. This was the initial presentation of AIDS in 6 patients accounting for 10.34% among all cases of HIV infection during that year. Both clinical and laboratory findings were subtle. Nuchal rigidity was rare, cerebro spinal fluid (CSF) cell count and protein level was normal in 3 out of 7 cases. Although culture for Cryptococcus was positive in all, it took 10 days to grow in 2 cases. India-ink stain showed scanty number of organisms in 3 cases. Low cell counts in CSF and presence of associated hyponatremia appear to be bad prognostic indicators in Cryptococcal infections of central nervous system. Latex agglutination test is a worthwhile screening test. PMID- 27407513 TI - Fecal Incontinence after Posterior Sagittal Anorectoplasty - Follow up of 2 years. AB - After an anorectal malformation (ARM) is repaired, the goal is fecal continence of the patient. Toilet training is not complete in children below 4 years of age. Manometric and radiological studies need cooperation of the child, and are therefore of little value during the critical preschool years. In this present study, we used only clinical criteria to assess the child for constipation and incontinence after definitive operation. We included all patients of ARM wef 01 April 1998 to 31 March 2000. Only 2 children had crossed 4 years of age at the time of this assessment and therefore it was not possible to assess total continence postoperatively. We found that the incidence of incontinence was less in low anomalies and more in high or intermediate anomalies, while the incidence of constipation was higher in low anomalies and less in high and intermediate anomalies. 31% of all patients born with anorectal malformations and subjected to posterior sagittal anorectoplasty (PSARP) approach were totally continent, 38% suffered with soiling of faeces while 31% had problems of constipation. The higher incidence of constipation as well as incontinence in our study is because of a short follow-up and secondly, these problems are known to improve with passage of time. The purpose of this article is to highlight the problems of bowel control even after the definitive operation and still much more is required to improve the quality of life of these unfortunate children. PMID- 27407514 TI - Behavioural Surveillance Survey Among Troops in a Large Military Station. AB - A cross sectional survey was carried out among the troops located in a large cantonment using the UNAIDS standard survey questionnaire (UN Best Practice Collection) for Behavioural Surveillance Survey (BSS). A total of 556 randomly selected recruits and soldiers were administered the questionnaire. The median age at first sexual encounter was 25 years for service personnel and 18 years for recruits. 5.5% of the recruits and 1.7% of regular soldiers reported having regular sexual partners other than spouse. Among those who had casual sex 46.3% reported using condoms. 52.3% were aware about the two main preventive indicators. Some incorrect beliefs regarding transmission of HIV/AIDS were also present among some of the respondents. The findings have been discussed in relation to previous studies. PMID- 27407515 TI - Transcervical Resection of Endometrium - Will it edge out Hysterectomy. AB - The most frequent indication for hysterectomy is menorrhagia, even though the uterus is normal in a large number of patients. Transcervical resection of the endometrium (TCRE) is a less drastic alternative, but success rates have varied and menorrhagia can recur. 60 patients with menorrhagia due to various causes who failed to respond to medical therapy and did not desire pregnancy and hysterectomy underwent TCRE with hysteroscope. 56 cases have been followed up postoperatively for 3 years. The primary endpoints were women's satisfaction and need for further surgery. The proportion of patients who attained amennorhea 24 months after the procedure was 44.4% and the percentage of patients who attained hypomennorhea was 44.4%. The patients satisfaction rate after 24 months of follow up was 88.8%. Failure of TCRE procedure was encountered in 6.6% of patients. Randomized comparison with hysterectomy has shown short-term benefits in the form of shorter operating time, fewer complications and faster rates of recovery and almost as high satisfaction levels. TCRE is an effective procedure in treating menorrhagia and is an acceptable alternative to medical management and hysterectomy in the treatment of menorrhagia for many women with no other serious disorders. PMID- 27407516 TI - 3-D Spiral Computerised Tomographic Angiography in Evaluation of Potential Renal Donors. AB - A total of 30 potential renal donors aged between 35 and 50 years were subjected to pre-operative 3-Dimensional Spiral Computerised Tomography (CT) angiography with the aim to assess its efficacy in the evaluation of renal vasculature. The investigations were carried out on a Philips Tomoscan AV Spiral CT scanner. Scan parameters included a collimation of 3 mm and table speed of 4 mm/sec. A total of 120 ml of non-ionic contrast was injected at a rate of 4 ml per second using a power injector. The axial images obtained were reconstructed at 2mm intervals and 3-D reconstruction was done using Surface Shaded Display (SSD) and Maximum Intensity Projection (MIP) protocols. CT angiography and its correlation with per operative findings revealed 97 to 100% sensitivity and specificity in identifying the main and accessory renal arteries and veins. The angiogram also excluded the presence of pathologies like polycystic kidney, horse shoe kidney with a thick isthmus and occult renal cell carcinoma that would prevent the patient from being a donor. 3-D spiral CT angiography allows the radiologist to provide the transplant surgeon with precise pre-operative anatomy of the renal vasculature thus reducing the risks and complications associated with the harvesting procedure and increasing the chances of a successful outcome. Thus it is a fast, accurate, inexpensive and minimally invasive procedure that is becoming the modality of choice for the pre-operative evaluation of potential renal transplant donors. PMID- 27407517 TI - Determinants of Smoking Habit among Medical Students. AB - A cross sectional study of smoking habits among medical students was carried out to find out the prevalence of smoking and its association with certain factors such as parental smoking, peer pressure, use of alcohol and other drugs. Prevalence of smoking was 46%. There was significant association of smoking with parental smoking habit, peer pressure, use of alcohol and other drugs. Strategies to counter these social determinants have been discussed. PMID- 27407518 TI - Appendicitis During Pregnancy. AB - Acute appendicitis is the most common extra-uterine surgical emergency requiring immediate surgical intervention during pregnancy [1]. Six young female patients presented with appendicitis during May 1996 to May 2001 in different service hospitals. Five patients underwent emergency appendectomy successfully. Gestational age at presentation included first trimester in 4 patients, second trimester in 2 patients and none in third trimester. 84% had pathologically proven acute appendicitis. One patient presented with appendicular lump in first trimester, proved on ultra sonography examination, which was treated by Oshner Sherren regime and subsequently interval appendectomy was done in second trimester. No long term adverse maternal morbidity or mortality was reported. One patient had premature onset of labour and delivered. Natural history of acute appendicitis is not changed during pregnancy while gestational physiological changes obscure the accurate diagnosis of acute appendicitis. PMID- 27407519 TI - Role of Biopsy from Gastric Corpus in Diagnosis of Helicobacter pylori Infection in Patients on Acid Suppression Therapy. AB - There are reports of migration of Helicobacter pylori from the gastric antrum to the proximal stomach following acid suppression therapy. The diagnosis of H pylori infection is usually based on rapid urease test and histology of gastric antral biopsies. 50 consecutive patients of peptic ulcer, 22 on proton pump inhibitors and 28 on histamine-2 receptor antagonists for at least 4 weeks were subjected to biopsies from the gastric corpus in addition to the antrum at the time of upper gastrointestinal endoscopy. H pylori infection was detected in 42 (84%) patients. The diagnosis was established from both antral and corpus biopsies in 34 (68%) and only antrum in 4 (8%). In 4 patients, 3 on proton pump inhibitors and one on H-2 receptor antagonists, H pylori was isolated only from the corpus. The rapid urease test was positive at a mean time of 67.6 minutes from the antrum as compared to 234.6 minutes from the corpus. Testing for H pylori from the antrum alone and not the corpus would have resulted in a false negative result in 8% patients. Biopsy from the gastric antrum should always be combined with biopsy from gastric corpus for the diagnosis of H pylori infection in patients with dyspepsia on acid suppression therapy. PMID- 27407521 TI - Immunization Coverage at a Military Station. AB - A study was conducted at a military station from Dec 2000 to Feb 2001, to study the exact immunisation coverage for six vaccines under Expanded Programme of Immunization (EPI Vaccines) and Hepatitis B vaccine and to find out unimmunized children. A house to house search was conducted and all the children below five years of age were included in the sample. Children of officers were excluded from the study. Overall 84.2% children were completely immunized for six EPI vaccines and 22.4% children were found to be immunised against Hepatitis B. The coverage for individual EPI vaccines is BCG (93%), DPT/OPV (91%), Measles (88%), DPT/OPV(B) (83%). The immunization coverage declined progressively for the vaccines given at higher ages from 93% for BCG given at birth, to 83% for DPT/OPV (B) given at 18 months of age. The immunisation coverage increased progressively with rank, being lowest in Sepoys (80.3%) and highest among Junior Commissioned Officers (97%). No statistically significant difference was found between static and field units, and the presence or absence of a Regimental Medical Officer in a unit for the immunization coverage. The study indicates that immunization coverage in the station is satisfactory, however efforts are needed to increase the vaccine coverage in the station. PMID- 27407520 TI - Amplatzer Device closure of Atrial Septal Defects and Patent Ductus Arteriosus: Initial Experience. AB - Surgical closure of Atrial Septal Defects (ASD) and Patent Ductus Arteriosus (PDA) can be performed successfully with low mortality. However, the morbidity associated with general anaesthesia, thoracotomy, cardiopulmonary bypass, postoperative monitoring in the intensive care unit, several days of hospital stay and the requirement of blood products is considerable. The expense associated with this morbidity, operative scar and the psychologic trauma to the patient and parents are additional disadvantages of surgery. Hence, the closure of these defects by transcatheter methods with various devices has been evaluated worldwide. We report the initial experience at our centre with closure of secundum ASDs and large PDAs with the Amplatzer Septal Occluder and Amplatzer Duct Occluder. PMID- 27407522 TI - Congestive Heart Failure in Infants and Children. PMID- 27407523 TI - Radiology Image Management in a Teaching Hospital Network Scenario: Initial Experience. AB - INHS Asvini has the distinction of emerging as the first Armed Forces Hospital with networked radiology images, sourced principally from a recently installed Digital Substraction Angiography (DSA) machine (Siemens Polystar Top 1000 MA). In recent times, newer imaging machines offer digital images that are in DICOM format. DICOM denotes 'Digital Imaging and Communications in Medicine". Image management at INHS Asvini, involves transfer of DSA images in DICOM format, their conversion into Joint Photographic Experts Group (JPG) format and subsequent transmission of JPG images through a robust networking system that connects all departments/OPD/Wards, facilitating direct access of images to a variety of specialists and specialities. Clearly, this encouraging outcome is a small but useful step heralding the concept of 'anytime anywhere' images, and has the scalable expansibility of including CT and MRI images in future. PMID- 27407524 TI - Acute Eye Conditions. PMID- 27407525 TI - A Training Aid for IV Access. AB - Starting intravenous drip is one of the first steps in the treatment of a patient. Training is the key to attain proficiency to get intravenous access. PMID- 27407526 TI - Sinonasal Mucormycosis: Diagnosis Using Computed Tomography. PMID- 27407527 TI - Pathological Quiz. PMID- 27407528 TI - Atypical Mycobacterial Injection Abscess. PMID- 27407529 TI - Granulomatous Rosacea or Tuberculid, A Histopathological Dilemma. PMID- 27407530 TI - Allergic Fungal Sinusitis with Mycetoma. PMID- 27407531 TI - Typhoid Fever Presenting as Acute Psychosis. PMID- 27407532 TI - Pulmonary Aspergilloma in Rheumatoid Arthritis. PMID- 27407533 TI - Radiological Quiz. PMID- 27407534 TI - Anaesthetic Management of a Case of Acromegaly in Remote Field Location. PMID- 27407535 TI - CHARGE Syndrome. PMID- 27407536 TI - Invasive to Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease. PMID- 27407537 TI - Mushroom Poisoning. PMID- 27407538 TI - Common Medicolegal Problems Faced by Medical Officers of Armed Forces. PMID- 27407539 TI - Building Safer Healthcare Systems: A Case for Error-in-Medicine Curriculum in Medical Training. PMID- 27407541 TI - Common Medicolegal Problems Faced by Medical Officers of Armed Forces: Reply. PMID- 27407540 TI - Patient Safety: Can the Armed Forces show the way? PMID- 27407542 TI - The Infusion Pump. PMID- 27407543 TI - Growth Disorders. PMID- 27407544 TI - Heart Failure: Current Concepts. PMID- 27407545 TI - Health Emergencies in Large Populations: The Orissa Experience. AB - Natural disasters occur frequently in the country and civic authorities requisition medical aid from the Armed Forces for the succour of populations, with increasing regularity. The recent Orissa floods (2001) saw deployment of a Medical Team and the experiences of the team are discussed. Over a nine day period, 7450 cases were treated on site in medical aid posts established in flood affected areas. Of these patients, 4038 (54.20%) were affected by gastrointestinal illnesses (diarrhoea/acute gastroenteritis); 976 (13.10%) had suffered injuries and were treated accordingly; 2007 (26.94%) cases of respiratory infection were managed. 210 (2.82%) cases of undiagnosed fever were treated, and 18 (0.24%) cases of clinical malaria were diagnosed additionally. Skin and other infections comprised 186 (2.50%) cases of the total. Thus, this study provides a brief outline of the spectrum of illnesses that may be encountered in dealing with flood affected populations, for the benefit of planning for future humanitarian operations. The various stages of a disaster have been brought out, for an insight into the morbidity pattern in such deployments. The concept of "Health Emergencies in Large Populations" is introduced in the discussion, for policy to be evolved. Public health is closely interlinked with disaster management, and the Army with its resource of trained specialists is geared for response in the face of disaster in a professional manner. Recommendations on dealing with future situations under such conditions of deployment have also been made. PMID- 27407546 TI - Missile Injuries of Brain - an Experience in Northern Sector. AB - During a period of one year, from Jan 99 to Dec 99, 60 cases of missile injuries were treated at our centre. 59 were males and one was a female and their average age was 25 years. 43 patients had suffered splinter injuries, 12 had gunshot wounds and 5 had suffered injuries by improvised explosive devices. Glasgow coma scale was < 5 in 8 patients, 5-8 in 14, 8-12 in 30 and 13-15 in 8 patients. Extensive comminution of skull bones was found in 10 patients. 35 patients had more or less clear penetration of the skull and the rest had orbito-cranial or facio-cranial wounds. CT scan revealed small haemorrhagic contusion with in driven bones without mass effect in 15, contusion with mass effect in 36 cases, cortical contusions without in driven bones (tangential injuries) in 3, distant intracranial contusions in 4, intraventricular haemorrhages in 5, multilobar injuries in 14, and unilobar injury in 40. 52 patients were operated upon at our centre of which 30 were operated within 24 hours, 10 between 24 to 48 hours, 12 between 48-72 hours. Six patients were treated conservatively and 2 required only simple closure of scalp wound. Craniectomy was done in 10 and craniotomy in 42 patients. Two patients developed wound sepsis, one each developed aspiration pneumonia, septicemia, deep vein thrombosis and post-traumatic hydrocephalus. On follow up at 6 months, outcome as per Glasgow outcome scale was as follows: good outcome - 42, moderate disability in 7, severe disability in 6 and death in 5 patients. Retained bone fragments were found in 40% on follow up CT scan but none had brain abscess. PMID- 27407547 TI - Collection, Separation, Enumeration and Cryopreservation of Umbilical Cord Blood Haematopoietic Stem Cells - An Experimental Study. AB - Cord blood as a source of haematopoietic stem cells (HSC) has several advantages as it is easily available, involves non-invasive collection procedure and is better tolerated across the HLA barrier. Since the first cord blood transplant in 1988, over 1000 cord blood HSC transplants have been done world wide. The present study was carried out for collection, separation, enumeration and cryopreservation of cord blood HSC. 30 samples of cord blood HSC were collected after delivery of infant prior to expulsion of placenta. The average cord blood volume collected was 101.33ml. Mononuclear cell count ranged from 7.36 to 25.6 * 10(7) ml. Viability count of mononuclear cells was 98.4%. After 6 months of cryopreservation, the viability count on revival was over 82.1%. PMID- 27407548 TI - Blood Ordering Strategies in the Armed Forces - A Proposal. AB - Over ordering blood is a common practice in medicine. This can be corrected by a simple means of changing the blood ordering pattern. A retrospective study was carried out in a tertiary care hospital of Armed Forces for a three year period to study the blood ordering strategies in the hospital. The total units demanded and the corresponding units issued were estimated. Thereafter, transfusion probability and ratio of units cross-matched to actual units transfused (C/T ratio) was calculated. In this study, using Mead's criterion, transfusion probability and C/T ratio, transfusion guidelines for all cases requiring transfusion is proposed. The study also identifies the common cases where 'Type and Screen' (T&S) procedure could be introduced in cases where the transfusion probability is low. The other group where transfusion probability is high, a maximum surgical blood ordering schedule (MSBOS) has been determined to identify the number of units to be cross-matched and kept ready before the procedure. The implementation of this proposal will avoid over-ordering of blood and will promote maximum utilization. PMID- 27407549 TI - Radiological Quiz. PMID- 27407550 TI - Restorative Proctocolectomy with Ileo-anal Reservoir, a Histopathological, Histochemical, and Electron Microscopic Study. AB - This study was conducted to investigate the nature of colonic metaplasia in ileo anal pouches and incidence/frequency of pouchitis in the same. Biopsy specimens from 8 patients with functioning ileal pouches were studied using routine histology, mucin histochemistry and electron microscopy, over a 2 - year period. All 8 patients had villous abnormalities in the form of blunting of villi and sub total or partial villous atrophy. 6 patients had an increase in the goblet cell population and Paneth cell hyperplasia. These changes were supported by electron microscopic findings of a decrease in number and flattening of ileal type microvilli and their transformed morphologic resemblance to colonic type microvilli. All the ileal pouches also had acquired colorectal type sulphomucin, when sections stained with Alcian-blue and High Iron Diamine - Alcian blue, were studied. However, no case of pouchitis as defined in literature, was found in this study. PMID- 27407551 TI - Conventional B-mode Ultrasonography for Evaluation of Retinal Disorders. AB - Sonographic study of 164 patients (328 eyes) in the present series highlights the advantages of ocular ultra sonography (B-mode) in the evaluation of retinal disorders especially in patients with opaque ocular media. B-mode sonography of the eye is a rapid, cheap, safe and reliable investigation for the eye. The sensitivity and specificity of this modality in detecting ocular pathologies has been recorded as extremely high and is of great value to the eye surgeon for a preoperative assessment of the posterior segment when fundoscopy is not possible due to opaque ocular media from various causes. PMID- 27407552 TI - Early Diagnosis of Human Immunodeficiency Virus Infection by p24 Antigen Detection. AB - p24 antigen was estimated in human immunodeficiency virus (HIV) sero-negative individuals attending various sexually transmitted diseases (STD) clinics and also in sero-negative voluntary blood donors. A total of 300 STD cases and 500 voluntary blood donors, who also acted as controls, were included in this study. Antibody to HIV was detected by ELISA and was confirmed by western blot. In sero negative individuals, p24 antigen detection was carried out by standard assay and immune-complex dissociation assay (ICD assay) using ELISA method and confirmation was done by neutralisation assay. In voluntary blood donors, 4 (0.8%) individuals were found to be HIV positive and no sero-negative individual was positive for p24 antigen. 41 out of 300 patients attending STD clinics were found to be positive for HIV and in 259 sero-negative patients, p24 antigen was detected in 6 (2.3%) cases by ICD assay whereas only 4 cases were detected by standard assay. By estimating p24 antigen an additional 2.3% HIV positive cases that were in window period were detected. Further, an ICD assay improves the detection of p24 positive individuals. PMID- 27407553 TI - Nuss Procedure for Pectus Excavatum - An early Experience. AB - The technique of minimally invasive repair of pectus excavatum is a new operation that allows for repair of this deformity without any cartilage resection or sternal osteotomy. The procedure has revolutionized the management of pectus excavatum. Six cases of pectus excavatum were referred to our centre for surgical correction. However, based on Haller's CT index 2 merited surgery. Our results suggest that the minimally invasive repair of pectus excavatum is an exciting operation with minimal morbidity and excellent results. The innovative incorporation of thoracoscopic techniques and small but important modifications to the techniques will make this operation very effective and safe. PMID- 27407554 TI - Endopyelotomy - a Minimally Invasive Surgical Option for Pelvi-ureteric Junction Obstruction: a Study Of 34 Cases. AB - We performed antegrade endopyelotomy in 34 cases in the last 21/2 years. In all cases standardized antegrade percutaneous method was used. A single guide wire and a cold knife were used to perform the endopyelotomy. Nephrostomy tube was retained for 48 hours and the repair stented for 6 weeks. Patients were followed up at 3 months, 6 months and 1 year post-operatively for subjective improvement and objectively by DTPA scans/IVU and ultrasound. The population included 2 bilateral cases, one horseshoe kidney and 3 children. The patient's age ranged from 9-59 years, average 32 years. There were 21 males and 13 females. 28 renal units were primary and 8 were secondary pelviureteric junction (PUJ) obstruction. Follow up period was 3-28 months. Most cases had significant symptomatic and functional recovery postoperatively. Five cases presented with urinary tract infection, which regressed after treatment. At 3(rd) month postoperatively the DTPA/IVU scan was equivocal in 7 cases. In these, a RGP was done which in every case showed a patent PUJ. In 5 cases that were still symptomatic, 6-8 weeks of further stenting produced symptom regression. Two cases failed and needed revision, one by open pyeloplasty and the other by endopyelotomy. Our success rate overall in these cases followed upto 1 year post operatively is 91.6%. We conclude that endopyelotomy is successful across a wide spectrum of cases. PMID- 27407555 TI - Cerebral Edema and its Management. PMID- 27407556 TI - Management of Common Otological Diseases at a Peripheral Medical Set Up. PMID- 27407557 TI - PG Canine Retraction Spring. PMID- 27407558 TI - Buccal Fat Pad Reconstruction in Oral Submucosal Fibrosis. PMID- 27407559 TI - Osteopetrosis. PMID- 27407560 TI - De Quervain's Thyroiditis. PMID- 27407561 TI - Recurrent Deep Neck Space Infections. PMID- 27407562 TI - Early onset Syphilitic Meningoencephalitis presenting as Abnormal Behaviour in a case of HIV Infection. PMID- 27407563 TI - Acute Incapacitating Hyperopia during Hypoglycemic Treatment. PMID- 27407564 TI - Gruber-Frantz Tumour. PMID- 27407565 TI - Neonatal Malaria: Report of two Cases. PMID- 27407566 TI - Organophosphorous Poisoning : an Evidence Based Approach. PMID- 27407567 TI - Anterior Cruciate Ligament Repair : Evolving Trends. PMID- 27407568 TI - Acinetobacter spp as Nosocomial Pathogen : Clinical Significance and Antimicrobial Sensitivity. AB - Acinetobacter spp are ubiquitous aerobic Gram negative coccobacillus, that are now increasingly responsible for a large number of nosocomial infections. In our study, over a period of six months (Jan-Jun 2000) at a tertiary care hospital, 152 (12.9%) isolates of Acinetobacter spp were obtained from a total of 1175 isolates grown from all clinical specimens. Most of the isolates 126 (82.9%) were from hospitalised patients in the spinal cord injury centre, intensive care units and those on prior antibiotic therapy. Community acquired infections were also seen in 26 (17.1%) out patient department (OPD) cases. Isolates were from urine, respiratory exudates, blood and pus/burn wound swabs predominantly. They were resistant to commonly used antibiotics while being sensitive to amikacin, augmentin, piperacillin, netilmicin and cefotaxime. 69.2% isolates exhibited resistance to two or more antibiotics. Clinical co-relation must be under taken to exclude commensal contaminants, before considering it to be a pathogen and prescribing antibiotics to the patient. PMID- 27407569 TI - Phacoemulsification : our experience at a large Military Hospital. AB - Cataract surgery by means of phacoemulsification was started at a large Military Hospital in March 2001. First 70 cases in whom phacoemulsification was performed between 15 March 2001 and 31 December 2001 were followed-up and evaluated. The surgical techniques used, complications and post-operative recovery following this new surgical technique have been discussed. Our experience of conversion from standard extracapsular cataract extraction to phacoemulsification has also been shared. PMID- 27407570 TI - Anterior Cruciate Ligament Reconstruction with Bone Patellar Tendon Bone Graft through a Mini Arthrotomy. AB - Instability after rupture of anterior cruciate ligament (ACL) may lead to recurrent episodes of giving way, an increased risk of meniscal injury and premature degenerative changes. A total of 25 cases with ACL injuries were evaluated after reconstruction with bone patellar tendon bone graft through a mini-arthrotomy. All patients were male. Maximum number of patients were between 25-30 years of age (40%). The most common modality of injury was contact sports (44%). Most common complaint was instability of knee (100%). Average Lysholm score increased from pre-operative of 47 (27-75) to post-operative of 87 (68-95). Two patients (8%) had retropatellar pain. Moderate to severe graft site tenderness was present in 4 (21%). After an average follow up of one year three months, the results were comparable with the results of arthroscopic reconstruction. PMID- 27407572 TI - Delirium Tremens. AB - The varied clinical manifestations and management of 14 male patients with delirium tremens (DT) have been studied. Eight patients were initially hospitalised for diseases unrelated to ethanol abuse i.e. 2 each for gun shot wound, myocardial infarction and stroke, and one each for pneumonia and gastroenteritis. One patient was going through withdrawal because of prodrome of viral hepatitis before he was hospitalised for uncontrolled agitation and delirium. Two known cases of mild essential hypertension on dietary therapy reported for agitation, abnormal behaviour, a single episode of tonic clonic seizure and hypertensive encephalopathy as they could not/did not get alcohol for 3 days. Three patients presented denovo with DT without concomitant illness. The other features besides delirium and hallucinations were tremulousness in 10, tachycardia in 12, fever in 3, diaphoresis in 2 and tonic clonic seizures in 4 patients. The symptoms fluctuated markedly at short intervals and 2 patients did not have any features of sympathetic overactivity. Altered hepatic biochemical parameters and ketonuria with normal blood sugar were noted in 4 and one patients respectively. Other biochemical parameters including serum electrolytes were normal. CT scan brain done for 5 patients revealed subdural haematoma in one. Cerebro spinal fluid (CSF) and EEG findings were noncontributory. All made good recovery with heavy doses of intravenous vitamin B complex, glucose and oral benzodiazepine. Short course of haloperidol was used in 2 patients. Two patients developed pancreatitis during follow up. All patients made complete recovery, and 8 patients have been followed for 8 to 12 months without relapse. The reason for hospitalisation in such cases is often unrelated to alcohol abuse; hence a detailed history of alcoholism is mandatory to identify those at risk as well as for prompt treatment and decreasing the mortality. PMID- 27407571 TI - Treatment of Casualties in a Forward Hospital of Indian Army : Nine year Experience. AB - BACKGROUND: To analyze the outcome of the management of casualties in a level II trauma centre of a forward hospital of Armed Forces over a nine year period. Retrospective analysis of all casualties received in a single forward hospital of Indian Army was carried out. METHOD: During 9 years (1990-1998), a total of 5737 casualties were received in a single level II zonal hospital of the Army in a forward area. Majority of the injuries were caused by bullets, or by fragments of improvised explosive devices. A policy of aggressive resuscitation and early primary repair of injuries was followed. General surgeons routinely performed craniotomies, thoracotomies, laparotomies, stabilization of fractures by fixators and repair of vascular injuries. RESULT: 38% of patients had injuries to several body parts (polytrauma), resulting in a total of 8578 injuries. Region-wise distribution of injuries was as follows : 14.2% head and neck injuries, 13.3% chest wounds, 13.5% abdominal injury and 59% extremity wounds. The overall mortality rate was 3.6%. The complication rate was about 7% with infection as the major complication. The results of primary repair of colonic injuries were similar to those of staged repairs. The results after primary closure of war wounds were better than those treated with delayed primary closure in selected cases. CONCLUSION: Prompt evacuation, speedy resuscitation and early definitive repair of war injuries results in low mortality and morbidity. A motivated and dedicated team and adequate availability of blood and ancillary services adds to the excellent outcome. The policy of primary repair of colonic and selected soft tissue injuries appears justified in selected cases. PMID- 27407573 TI - Laparoscopic Management of Adnexal Masses. AB - Retrospective study of 121 cases of adnexal masses which were managed laparoscopically was carried out. The aim of study was to evaluate the safety and effectiveness of laparoscopic management of adnexal masses. In 120 cases, procedure was completed safely with minimum morbidity. In one case laparotomy had to be done to complete the procedure. In 76 cases cystectomy was done, 26 required salpingo-oophorectomy and 19 required only salpingectomy. Histologic evaluation revealed 30 functional cysts, 36 endometriotic cysts, 11 dermoids, 9 serous cystadenomas, 3 mucinous cystadenomas, 11 parovarian cysts, 19 cases of hydrosalpinx and 2 cases of tuberculosis. PMID- 27407574 TI - Day Care Surgery in Otolaryngology : a three year Prospective Study. AB - Day care surgery is now an integral part of otolaryngology and is widely practised in the West. But in our military setup it still has to gain popularity. A Day Care Surgical Centre was established at Armed Forces Clinic in 1996. In the period May 1998 to Apr 2001, a total of 752 otolaryngology cases were operated at the centre, of which 474 cases were major and 278 cases were minor. All cases were performed under local anaesthesia supplemented by sedation. Strict patient selection criteria were adopted resulting in a low immediate post-operative complication rate (1.46%). None required admission to hospital for the management of complications. The feasibility of performing otolaryngological surgery on a day care basis is demonstrated, especially in nasal and aural cases. The experience gained shows that high medical standards can be achieved with low resource expenditure. Patient selection criteria and guidelines are suggested. PMID- 27407575 TI - Growth Hormone and Prolactin Secretion after External Cranial Irradiation for Extrasellar Tumours. AB - BACKGROUND: Deficiency of one or more anterior pituitary hormones may follow treatment with external radiation when hypothalamo-pituitary axis lies within the field of radiation. Patients with brain tumours who are treated with radiation frequently have growth hormone (GH) deficiency, other neuro-endocrine abnormalities are presumed to be uncommon. The present study has been undertaken with the aim to study GH and prolactin secretion, their relationship with dose of radiotherapy and duration after radiotherapy in patients who have received extracranial radiation for extrasellar tumours. METHOD: In this study, 96 patients who underwent cranial radiation before 12 months, were evaluated. Basal 8 a.m. venous blood samples were taken for estimation of prolactin and GH. Insulin tolerance test was performed for stimulated GH levels. RESULT: GH deficiency was present in 59% patients. Isolated GH deficiency was present in 12 (21%) cases, whereas others had associated hormone deficiency. Height percentiles of prepubertal and pubertal patients were 10(th) to 25(th) (-1.5 to -0.5SD). Patients with isolated GH deficiency had received significantly higher radiation dose than normal pituitary function (5795 +/- 24 vs 4908 +/- 71, p=0.001). Proportion of patients with GH deficiency increased with increasing dose of radiation (p=0.12), fractional dose of radiation (p=0.08) and increasing duration after radiotherapy (p=0.038). GH levels among all decreased significantly with increasing dose of radiation (p=0.02). Hyperprolactinemia was present in 21% of cases. GH deficiency is more common with lower (<5ng/ml) and higher (>15ng/ml) prolactin levels. CONCLUSION: GH deficiency is common after extracranial radiation for extrasellar tumours. GH deficiency is related to dose of radiation, fraction of radiation, and duration after radiotherapy. All prepubertal and pubertal patients with GH deficiency had their height percentile within normal range. Relation of prolactin and GH deficiency indicates that radiation affects both hypothalamus and pituitary. PMID- 27407576 TI - Assessment of Uterine Factor in Infertile Women : Hysterosalpingography vs Hysteroscopy. AB - The objective of this study was to evaluate the diagnostic accuracy of hystero salpingography (HSG) in detecting uterine cavity abnormalities in infertile patients, with reference to hysteroscopy as the gold standard method. 60 infertile women were investigated with both HSG and hysteroscopy. Statistical analysis was performed. As a test for the detection of uterine cavity abnormalities, HSG in comparison with hysteroscopy had 60% sensitivity, 90% specificity, 10% false positive value and 40% false negative value. HSG is not able to diagnose polyps, septum and submucous fibroids with significant accuracy. Therefore hysteroscopy is indicated for confirmation. PMID- 27407577 TI - Effect of Cryopreservation on Semen Sample. AB - There are varied indications of preserving a semen sample for utilization at a later day. However, the freeze-thaw cycle is bound to impart deleterious effect on the fertilizing potential of the sample. 60 semen samples divided into three groups were preserved in this study. On subsequent thawing, after three months it was seen that the yield varied between 66% to 72%. The post thaw percent yield bears a linear relationship with the pre-freeze quality. 5 pregnancies were achieved in the study testifying the preservation of fertilizing ability of the thawed samples. Sub normal semen samples which might be otherwise acceptable in a therapeutic insemination, do not withstand freezing. PMID- 27407578 TI - Cytokines : as useful Prognostic Markers in Lymphoma Cases. AB - Cytokines are believed to be involved in the pathogenesis and enhanced expression in patients with Hodgkin's and Non-Hodgkins lymphoma. Based on this phenomenon, a multicentric study was carried out in various lymphoma cases. The diagnosis of lymphoma was made on tissue biopsies and fine needle aspiration cytology (FNAC). Out of a total of 72 cases studied, 45 were of Hodgkin's lymphoma (62.5%) and 27 cases were of Non-Hodgkin's lymphoma (37.5%). Maximum cases of Hodgkin's disease occurred in the age group of 30-40 years and males outnumbered females. Hodgkin's lymphoma cases were predominantly of mixed cellularity histologic type (46.66%) whereas majority cases of Non-Hodgkin's lymphoma were of high grade histologic type (48.14%) with predominance in the age group 51-60 years. In both these type of lymphomas, the IL-2R and IL-6 levels were found to be increased more than four fold (as compared to healthy controls) (p<0.05). The cytokine levels decreased after chemotherapy in patients showing response to therapy. However, there were few conflicting and unreliable trends in the IL-6 levels after chemotherapy where elevated IL-6 levels persisted in patients in clinical remission. Overall, it was seen that both IL-2R and IL-6 can be used as an indicator for assessing prognosis and drug therapy in lymphoma cases. IL-2R was found to be a better prognostic marker than IL-6 in assessing the response of lymphoma patient to chemotherapy, more so in Hodgkin's disease. PMID- 27407579 TI - Cardio-pulmonary Resuscitation : an overview of Recent Advances in Concepts and Practices. PMID- 27407580 TI - Psychiatric Emergencies. PMID- 27407581 TI - Designing Hospital for better Infection Control: an Experience. AB - The physical design of hospital is an essential component of a hospital's infection control strategy, incorporating infection control issues to minimise the risk of infection transmission. Hospital design therefore, needs to consider the separation of dirty and clean areas, adequate ventilation, lighting and storage facilities and design of patient accommodation areas, including adequate number of wash hand basins and single bed facilities. A 250 bed general hospital was planned keeping in view structural and design elements necessary for success of a good infection control programme. Various National and International Standards like BSI recommendations, JCAHO, IC Standards, DHSS, ASHRAE, AIA and OSHA were studied and compared with our planning parameters. Planning of ward unit, ICU, Operation theatre and Isolation wards were especially reviewed in the light of recent knowledge available in the field of hospital acquired infection and modifications were carried out. Need for effective identification of potential infections, risks in the design of a hospital were stressed. Engineering controls required to reduce the concentration of infectious droplet nuclei in the air and prevention of transmission of disease were highlighted. PMID- 27407583 TI - Beckwith Weidemann Syndrome. PMID- 27407582 TI - Multifetal Pregnancy Reduction. PMID- 27407584 TI - Aesthesioneuroblastoma of Nose. PMID- 27407585 TI - Klippel - Trenaunay Syndrome. PMID- 27407586 TI - Nasal Polyp : a Rare Presentation of Hypereosinophilic Syndrome. PMID- 27407587 TI - Limb Body Wall Complex. PMID- 27407588 TI - Ehlers-Danlos Syndrome Type V. PMID- 27407589 TI - Acute Flaccid Paralysis. PMID- 27407590 TI - Xanthogranulomatous Pyelonephritis : Diagnosis using Computed Tomography. PMID- 27407591 TI - Scrub Typhus, a Case Report : Military and Regional Significance. PMID- 27407592 TI - IODIZED SALT IN THE ARMED FORCES - USAGE FOR BENEFIT. PMID- 27407593 TI - SECURITY AWARENESS. PMID- 27407594 TI - AGGRESSIVENESS - THE KEY TO A SUCCESSFUL OUTCOME IN NECROTIZING SOFT TISSUE INFECTION. PMID- 27407595 TI - NICU ENVIRONMENT. CAN WE BE IGNORANT? PMID- 27407596 TI - AGGRESSIVENESS - THE KEY TO A SUCCESSFUL OUTCOME IN NECROTIZING SOFT TISSUE INFECTION: REPLY. PMID- 27407597 TI - NICU ENVIRONMENT. CAN WE BE IGNORANT?: REPLY. PMID- 27407598 TI - Changing Practice of Gynecologic Oncology based on Current Evidence. PMID- 27407599 TI - HIV / AIDS : Social and Ethical Issues. PMID- 27407600 TI - Effect of short-term Psychiatric Intervention in Cancer Patients. AB - A total of 50 patients undergoing cancer treatment at Malignant Disease Treatment Centre were included in the present study aimed at evaluating the psychological status of cancer patients. All patients filled a specially designed proforma and the following psychological questionnaires : General Health Questionnaire, Carroll Rating Scale for Depression, State-Trait Anxiety Inventory, PGI General Well-being Scale and Quality of Life Scale. Analysis of the results showed that 22 (44%) of the cancer patients had psychiatric disorders and this number had reduced to 12 (24%) after therapy. The difference was statistically significant. Psychiatric treatment also resulted in a statistically significant reduction in level of depression as measured by Carroll Rating Scale for depression. Short term psychiatric treatment was found to be very useful in treating psychiatric morbidity and depression in cancer patients. PMID- 27407601 TI - Prospective Study on the Morbidity Profile of Recruits over one year in three large Regimental Training Centres. AB - Keeping in view the lack of prospective epidemiological data on the incidence of major causes of morbidity specifically among recruits, the present study was undertaken among recruits of three large regimental training centres in a particular cantonment. The study period extended over exactly one training year, from 01 July 2001 to 30 June 2002. Successive batches of recruits entering the training centres during this period were followed up prospectively for hospitalisation in the local military hospital, till they completed their training. The study revealed that the major causes of morbidity were chickenpox and training injuries, including stress fractures. The major causes of invalidments were injuries, pulmonary tuberculosis and mental disorders. The findings have been compared and certain recommendations for preventing / reducing the incidence of major causes of morbidity have been submitted. PMID- 27407602 TI - Vascular applications of Spiral CT : an initial Experience. AB - Since the clinical introduction of computed tomography (CT) in the mid 1970s, several technological and clinical advances have improved image quality and reduced scanning time. During the past decade technological breakthroughs have ushered in an exciting advance in medical imaging : spiral CT. Spiral CT technology with its high speed and volumetric data acquisition has spawned a new vascular imaging technique - spiral CT angiography which is noninvasive, accurate, faster and less expensive than conventional angiography. We report our experience of having performed 100 CT angiographies with 3-D reconstructions of various vascular territories of the body. Details of technique of data acquisition, methods of 3-D reconstruction and clinical applications are discussed. PMID- 27407603 TI - Pain relief following Arthroscopy - a comparative study of Intra-articular Bupivacaine, Morphine and Neostigmine. AB - Pain after arthroscopy is quite distressing. Intra-articular bupivacaine produces transient analgesia and reports of analgesia using intra-articular opioids have produced conflicting results. Recently, spinal administration of neostigmine was shown to produce dose-dependant analgesia. However, this was limited by adverse effects. The purpose of this study was to compare the effects on intra-articular neostigmine, bupivacaine and morphine. 75 patients were randomized to receive intra-articular saline, bupivacaine, morphine, neostigmine and bupivacaine neostigmine after arthroscopic surgery under spinal anaesthesia. Visual analog pain scores (VAS), duration of analgesia as defined as time for first demand for parenteral opioids and the total subsequent consumption of morphine was evaluated. Intra-articular bupivacaine resulted in significant VAS reduction at one and four hours as compared to those receiving intra-articular saline and morphine. Analgesia lasted longer after 500ugm intra-articular neostigmine as compared with bupivacaine, morphine or saline. The need for supplementary analgesia was lowest in the neostigmine group as compared to the other groups. No significant difference was found if bupivacaine was added to neostigmine. Among all the groups, no significant side-effects were observed. PMID- 27407605 TI - Sutureless closure of Operative Skin Wounds. AB - Good tissue union and cosmetically acceptable scar is vital for ideal surgical practice. Since their discovery in 1949, cyanoacrylate compounds have evoked interest as being the ideal "tissue glue". Several different forms of this compound have been developed in order to eliminate tissue toxicity. In this article, we have described a technique of sutureless closure of operative skin wounds and compared it to closure of skin with silk. Inter-group comparison was carried out with respect to the time required for closure, rate of infection, cosmesis and patient acceptance. N-butyl 2-cyanoacrylate was used for sutureless skin closure in 100 patients and compared with skin closure with sutures. The time taken to close the wounds with cyanoacrylate was found to be significantly less, the cosmetic outcome better and patient acceptability higher than when sutures were used. PMID- 27407604 TI - Treatment of Allergic Bronchopulmonary Aspergillosis with Fluconazole and Itraconazole. AB - Treatment of allergic bronchopulmonary aspergillosis (ABPA) has remained both problematic as well as controversial. Although the sheet anchor in treatment of ABPA still remains steroids, various workers have tried oral antifungals (fluconazole and itraconazole) with encouraging results. This study evaluates the effect of fluconazole or itraconazole in the treatment of ABPA patients and compares them with the patients who had received palliative therapy other than antifungals. Case records of 44 proven cases of ABPA treated at our referral service hospital during February 1998 to April 2001 were analyzed. In addition to oral and inhaled bronchodilators, 16 patients received fluconazole 150 mg OD and 13 patients itraconazole 200 mg OD for six months. Response to therapy was assessed clinically, radiologically and by spirometry every 3 months. Patients who did not receive antifungals had chronic course characterized by airway obstruction, recurrent pulmonary consolidation and obstructive defect on pulmonary function test (PFT). Patients treated with itraconazole had better control of asthma symptoms, less requirement of reliever inhalers, steroids and lesser exacerbations of asthma during follow-up even after stopping antifungal. Fluconazole group had better control of symptoms but improvement in other parameters was not statistically significant. From this study it was evident that itraconazole improved the symptoms of airway obstruction, pulmonary functions, pulmonary opacities and decreased exacerbations during follow up. PMID- 27407606 TI - Incidence and Drug Susceptibility pattern of Mycobacterium tuberculosis in HIV infected Patien. AB - Incidence of HIV infection in patients with tuberculosis was found out by serological method (ELISA) with confirmation by Western Blot analysis. Out of 2116 tuberculosis patients tested for HIV, 150 cases were found to be positive for HIV infection (5.73%). Drug susceptibility to first line antitubercular drugs was carried out in 1378 isolates from HIV negative cases and 68 isolates from AIDS cases. The overall resistance pattern to one or more drugs was seen in 13.78% of isolates from HIV negative cases as compared to 7.2% isolates in AIDS cases. Multidrug resistance (MDR) was seen in 8.9% of isolates from HIV negative cases as compared to 4.4% of isolates from AIDS cases. PMID- 27407607 TI - Saving Private Ryan: The Indian Scenario (Rapid Diagnosis of Malaria at Regimental Aid Post). AB - Immunochromatography test (ICT) (Paracheck Pf) for diagnosis of Plasmodium falciparum (Pf) infection was compared with the conventional smear examination method. A total of 350 specimens of blood from cases of fever were investigated (falciparum malaria 220, vivax malaria 100, controls 30). Paracheck Pf ICT was found to have enormous advantages over smear examination due to its high degree of sensitivity, specificity, speed and ease of performance. Paracheck Pf ICT test kits are stable at room temperature. Regimental medical officers (RMOs) and nursing assistants with minimal training can safely practise Paracheck Pf ICT method. Introduction of this test method in the Armed Forces can facilitate early diagnosis and specific treatment of falciparum malaria even at far flung places. This will have enormous beneficial effect in reducing morbidity due to malaria and saving precious lives. In short as well as long term, it is a viable cost effective option. PMID- 27407608 TI - Aggressiveness - the key to a successful outcome in Fournier's Gangrene. AB - Nine patients with Fournier's gangrene were managed during last five years in various service hospitals. Mean age was 51 years (range 21-81 years). Most of these patients were from middle and upper class. Common predisposing factors included diabetes mellitus, alcohol abuse and poor personal hygiene. Streptococcus haemolyticus, Staphylococcus aureus and E coli were the commonest organisms cultured in most of these patients. Our experience indicates that the lower gastrointestinal tract should be considered as a possible cause of infection in all patients with Fournier's gangrene as 5 patients developed this condition following anorectal abscesses. All these patients were treated with a common approach of resuscitation, broad spectrum antibiotics, immediate surgical excision of all necrotic tissue, nutritional therapy and early skin coverage without any mortality. The surgeon should be more aggressive in the initial therapy and make the first surgery more definitive. There is no place for conservative management. The patients with perianal sepsis in elderly should be referred early for surgery. PMID- 27407609 TI - Clinical profile of Solitary Seizures. AB - BACKGROUND: Solitary seizure is one of the controversies in neurology. This study was taken up to study the clinical profile of solitary seizure and the factors related to seizure recurrence with a view to evolve guidelines for management. METHODS: We studied 150 cases of solitary seizure. All our patients were males. The age varied from 18-52 years. The diagnosis of seizure was confirmed with history. Apart from clinical neurological examination, blood counts, urinalysis and screening investigations to exclude possible underlying metabolic disorders were done. Inter-ictal EEG and contrast enhanced CT scan were done. RESULTS: CT scan was abnormal in 28 cases. EEG was abnormal in 33; clinical abnormality was noted in 15 cases. Median follow up duration was 1.2 years. 18 patients had seizure recurrence. Type of seizure, EEG findings (normal or abnormal) and treatment with antiepileptic drugs did not have any effect on seizure recurrence. Seizure recurrence was less common in presence of CT scan abnormality though it was not significant statistically. Routine laboratory tests of blood count, blood sugar and urinalysis were normal in all cases. CONCLUSION: In cases of solitary seizure, type of seizure, results of EEG and CT scan findings are not likely to predict seizure recurrence. Treatment with antiepileptic drugs does not prevent seizure recurrence. Laboratory investigations like blood counts, urinalysis and blood sugar estimation are unlikely to be of value in routine work-up of these cases. PMID- 27407610 TI - Dermatology : the past Milestones and the future Cross-currents. PMID- 27407611 TI - HIV Vaccine Strategies - an Update. PMID- 27407612 TI - Cold Injuries : The Chill Within. PMID- 27407614 TI - Remifentanil hydrochloride : an Opioid for the 21(st) Century. PMID- 27407613 TI - The role of perception in Medication Errors : Implications for Non-Technological Interventions. PMID- 27407615 TI - Delivering Oxygen during Nebulization to Infants and Toddlers. PMID- 27407616 TI - High Altitude induced Ortner's Syndrome. PMID- 27407617 TI - Malaria and Human Immunodeficiency Virus Infection. PMID- 27407618 TI - Glucocorticoid-resistant Bronchial Asthma. PMID- 27407619 TI - Pulmonary Oedema in a survivor of Suicidal Hanging. PMID- 27407621 TI - A case of Fracture in a Newborn delivered by Caesarian Section. PMID- 27407620 TI - Resurfacing of Amputation Stumps using free Tissue Transfer. PMID- 27407623 TI - Nuclear Imaging in Meckel's Diverticulum. PMID- 27407622 TI - Neonatal Polycythaemia. PMID- 27407624 TI - Glomus Tympanicum. PMID- 27407626 TI - IMMUNIZATION COVERAGE AT A MILITARY STATION. PMID- 27407625 TI - Cervical Thymic Cyst. PMID- 27407627 TI - IMMUNIZATION COVERAGE AT A MILITARY STATION: REPLY. PMID- 27407628 TI - EVOLVING MEDICAL STRATEGIES FOR LOW INTENSITY CONFLICTS - A NECESSITY. PMID- 27407629 TI - OUR STRESS-PROOF JAWAN. PMID- 27407630 TI - PATIENT SAFETY & HEALTH CARE. PMID- 27407631 TI - EARLY CONGENITAL SYPHILIS: FORGOTTEN BUT NOT. PMID- 27407632 TI - PATIENT SAFETY & HEALTH CARE: REPLY. PMID- 27407633 TI - Newer Perspectives of Childhood Asthma. PMID- 27407634 TI - From the Editor's Desk. PMID- 27407635 TI - Thrombosis - The Newer Dimensions. PMID- 27407636 TI - Laparoscopic Management of Ectopic Pregnancies. AB - To compare the laparoscopic approach with laparotomy in the treatment of ectopic pregnancy, a retrospective analysis involving 52 patients with ectopic pregnancies was done. The aim of this study was to evaluate the safety and efficacy of laparoscopic surgery for ectopic pregnancies. 30 patients underwent laparoscopic management while 22 patients were managed by conventional laparotomy. In the laparoscopic group, the postoperative morbidity and post hospital stay were significantly less. Although laparoscopic surgery for ectopic pregnancies is a new approach and it is not widely practised in service hospitals, it has more advantages than open surgery and it has been well accepted by the surgeons and patients. It is a safe and feasible approach. PMID- 27407637 TI - Noninvasive Positive Pressure Ventilation in Patients with Acute Respiratory Failure. AB - Noninvasive positive pressure ventilation (NIPPV) delivered by nasal route or facemask is increasingly being used in the management of patients with acute respiratory failure. 45 patients (29 males,16 females) with a mean age of 68.32 years (range 29 to 82 years) having acute onset hypoxemic and/or hypercapnic respiratory failure who were managed with NIPPV in a tertiary care centre of Armed Forces were analyzed retrospectively. Patients with hemodynamic instability, coma and uncooperative patients were excluded from study. Etiology of acute respiratory failure was acute exacerbation of chronic obstructive pulmonary disease (COPD) in 29 patients, adult respiratory distress syndrome (ARDS) in 4 patients, severe kyphoscoliosis in 2 patients, interstitial lung disease (ILD) in 4 patients, lung contusion with pneumonia in 1 patient, thoracoplasty in 1 patient and difficult weaning in 4 patients. Initial resting arterial blood gases showed mean arterial oxygen tension (PaO2) 61 mmHg (range 45 to 78 mmHg), mean arterial carbon dioxide tension (PaCO2) 75.2 mmHg (range 32 to 127 mmHg) and mean arterial pH-7.26 (range 7.03 to 7.45). Mean inspiratory positive airway pressure (IPAP) was 14 cm H2O (range 10 to 20 cm H2O). Mean expiratory positive airway pressure (EPAP) was 5.8 cm H2O (range 4 to 8 cm H2O). On an average, NIPPV was required for 5.4 days (range 2 to 15 days) prior to discharge. 11 patients required long term intermittent NIPPV along with domiciliary oxygen therapy. 9 patients died out of which 4 patients had advanced interstitial lung disease. NIPPV has been found useful in acute respiratory failure due to acute exacerbations of COPD, thoracic wall abnormalities and ARDS. It has not been found useful in hypoxemic respiratory failure due to interstitial lung disease and diffuse interstitial pneumonia. PMID- 27407638 TI - Distraction - A Minimally Invasive Technique for Treating Camptodactyly and Clinodactyly. AB - Camptodactyly and clinodactyly are relatively common congenital anomalies affecting about 1% to 2% of the general population. Though functional impairment is uncommon other than in very severe cases, patients affected do present very often for correction. The kind of surgeries available is as diverse as the aetiology of the conditions. It ranges from simple release of the flexor digitorum sublimis (FDS) to more complex small muscle transfers, rebalance etc. In this short series a relatively easier, minimally invasive technique of distraction has been used to correct these deformities with gratifying results. PMID- 27407639 TI - Effect of Short-term Psychiatric Intervention in Amputees. AB - A total of 40 patients with limb amputations were included in the present study aimed at evaluating the psychological status of amputees. All patients filled a specially designed proforma and the following psychological questionnaires: General Health Questionnaire, Carroll Rating Scale for Depression, State-Trait Anxiety Inventory, Michigan Alcoholism Screening Test and Disability Assessment Questionnaire. Analysis of the results showed that 29 (72.5%) of the amputees had psychiatric disorders and this number had reduced to 20 (50%) after therapy. The difference was statistically significant. Psychiatric treatment also resulted in a statistically significant reduction in level of depression as measured by Carroll Rating scale for Depression. The amputees had the highest score on vocational subscale of Dysfunction Analysis Questionnaire. Short term psychiatric treatment was found to be very useful in treating psychiatric morbidity and depression in amputees. PMID- 27407640 TI - The Challenge of Enterocutaneous Fistulae. AB - During a period of six years, 17 cases of enterocutaneous fistulae arising from the small intestine were managed. Majority of the fistulae, (76%) resulted from surgical complications. There were 6 females and 11 male patients. The mean age of the patients was 40 years. In 9/17 patients (52%) the fistulae arose from the proximal small gut (duodenum and jejunum) and in the remaining 48% from the ileum. Octreotide was used in 11/17 patients (64%). Enteral nutrition was used in 9/17 patients (52%) while re-feed from the proximal gut fistulae was used in 4/9 patients (44%) to maintain the nutrition of the patients. Only one fistula (6%) closed spontaneously. There were 2 deaths (12%) in this study. 14/17 patients (82%) required surgical intervention at some stage for successful closure of intestinal fistula. Aggressive surgical treatment with judicious use of octreotide, nutritional support, stoma care and control of sepsis significantly improves the outcome of small intestinal fistulae. PMID- 27407641 TI - Orocutaneous Manifestations as Markers of Disease Progression in HIV Infection in Indian Setting. AB - CD4, CD8 and absolute lymphocyte counts (ALC) were carried out by flowcytometry in 36 HIV-infected cases with various orocutaneous manifestations, 50 asymptomatic HIV infected individuals and 50 HIV-negative controls. Average CD4 counts and CD4 : CD8 ratio in symptomatic HIV-infected cases were found to be 245.39/cmm and 0.27 respectively, significantly lower than that of HIV-infected asymptomatic individuals (622.4 and 0.45 respectively) and HIV-negative controls (798.81 and 1.03 respectively). Patients with one (77.78%), two (19.44%) and three (2.78%) orocutaneous manifestations had average CD4 counts of280.25, 131.3 and 68/cmm respectively. All the 7 cases with oral mucosal candidiasis had CD4 counts lower than 200/cmm (average 105.28/cmm), thus fulfilling AIDS-defining criteria. Although 6 (85.71%) of the 7 cases had CD4 counts less than 200, Herpes zoster should not be considered as an AIDS-defining illness, as the HIV-infected who had had H zoster in the past had higher CD4 count (average 299/cmm). Dermatoses like seborrhoeic dermatitis and lichen planus, and some infections and infestations like scabies, bacillary angiomatosis, human papilloma virus infection, molluscum contagiosum and dermatophytosis cannot be considered as AIDS defining illnesses per se. PMID- 27407642 TI - Effectiveness of Teaching of Neonatal Resuscitation Programme at a Workshop for a Mixed Population of Medical Personnel. AB - We evaluated the effectiveness of teaching at a neonatal resuscitation programme (NRP) workshop held for 35 medical personnel (including postgraduate trainee doctors, general duty medical officers, nursing officers and probationer nurses) using a one-group pretest-posttest design. None of the participants had any formal exposure to the NRP guidelines. A pre-workshop test of 20 multiple-choice questions was administered to all the participants. At the end of the workshop, the same 20 questions were administered and the two scores compared using t-test for paired data on SPSS statistical software. The mean pre-workshop score was 9.03 (SD 2.66) which improved to a mean of 15.53 (SD 1.93) post-workshop. This improvement was highly significant with p < 0.0001 (two-tailed) and the 95% confidence interval being -7.41 to -5.59. Subgroup analysis revealed that nursing officers and probationer nurses showed highly significant improvement in the post workshop scores while trainee doctors doing Medicine, Pediatrics and the general duty medical officers showed statistically significant improvement in the post workshop scores. This study shows that a medical workshop is an effective means of imparting knowledge to a mixed group of medical personnel. PMID- 27407643 TI - Outcome of Treatment of Alcohol Dependence Syndrome Patients in Military Psychiatry Set Up. AB - BACKGROUND: Many people believe that patients suffering from Alcohol Dependence Syndrome do not respond much to treatment. Such belief may adversely affect the treatment of these patients. This may also alter the attitude of administrators on disposal of these patients. In this study, an attempt was made to observe the treatment outcome of patients suffering from Alcohol Dependence Syndrome. METHOD: Medical documents of all patients suffering from Alcohol Dependence Syndrome who reported for follow up in a general hospital psychiatric centre during the period of 1995-2000, were scrutinized. Patients were divided into three categories - those who were in relapse, those who improved partially and those who maintained abstinence. RESULTS: Out of 341 cases, 146 patients were reviewed after six months, 57 after one year, 50 after one and half years and 88 were reviewed at 2 years and above. When a total was made about the number of relapses, partial improvement and abstinent cases, it was found that 33.16% had relapses, 35.49% cases showed partial improvement and 31.35% cases were abstinent. CONCLUSION: The result was contrary to a prevailing belief that these patients do not respond much to treatment. It showed that two third of the patients improved, out of which one third were abstinent at the time of review. This study is likely to encourage the doctors, patients and administrative authorities to seek treatment of patients suffering from Alcohol Dependence Syndrome as treatment definitely helps many of them. PMID- 27407644 TI - Epidemiological Differentials of Hepatitis B Carrier State in the Army : A Community Based Sero-epidemiological Study. AB - BACKGROUND: Most available studies on seroprevalence of Hepatitis B in the Armed Forces and also at the national level are based on hospital patients and blood donors. Hence, there was a perceived need to undertake a seroepidemiological study on an adequately large and representative random sample of the general cross section of Army personnel, with a view to obtain the exact picture of the frequency and distribution of HBV in the Army. METHODS: A community based cross sectional study with random samples from four groups were drawn, viz recruits from the Army Medical Corps (AMC) and other Arms and Services; AMC personnel and personnel from other Arms and Services who had served for more than 10 years. A structured pretested questionnaire was administered to all participants and blood samples were drawn aseptically subsequently, with separation of serum and testing by ELISA technique for HBsAg. Multivariate analysis using multiple logistic regression procedure was done after appropriate data entry. RESULTS: The overall seroprevalence was 7.9% (95%CI = 6.5% to 9.26%). The differential seroprevalence in the four groups being 7.72%, 7.92%, 8.28% and 7.75% respectively. There was statistically no significant difference as regards the seroprevalence levels [p > 0.05]. As regards serving medical personnel, the seroprevalence was observed to be higher among personnel involved in direct nursing care. On multiple logistic regression analysis, two risk factors emerged as independent and significant predictors of hepatitis B positivity. These were history of sexual exposure with commercial sex workers (CSWs) (OR = 3.06, p < 0.01) and history of having taken injections from civil sources (OR = 1.92, p < 0.001). CONCLUSION: The relatively high level of seroprevalence among recruits has led to certain recommendations on testing and further studies in specific groups, based on the findings of the study. PMID- 27407645 TI - Clinical Evaluation Versus Echocardiography in the Assessment of Rheumatic Heart Disease. AB - BACKGROUND: Rheumatic heart disease (RHD) is still a common form of heart disease among children and young adults, especially in developing countries like India. Between 1940 and 1983, the prevalence rate of RHD varied from 1.8 to 11 per 1000 (national average 6 per 1000), while between 1984 and 1995 the rate varied from 1 to 5.4 per 1000 [1]. The study was carried out to assess the accuracy of a medical student's clinical evaluation of valvular heart disease and compare it with that of an echocardiographic evaluation and to determine the sensitivity, specificity and predictive values of clinical examination as compared to echocardiography for the various lesions in RHD patients. METHOD: 50 children between the ages of 5-16 years, attending the out patient department or admitted in a large teaching hospital, satisfying the criteria of RHD, were included in the study. Each patient underwent detailed clinical evaluation and relevant investigations including echocardiography. RESULTS: Mitral valve was involved most often both by echocardiography and clinically. Isolated aortic valve involvement was rare. The most common lesion was mitral regurgitation (MR) both by auscultation and by echo. Mixed lesions were seen more often than pure lesions. Mitral stenosis (MS) had the highest sensitivity while tricuspid regurgitation (TR) had the highest specificity. MR had the highest positive predictive value and MS the highest negative predictive value. Sensitivity and specificity of aortic regurgitation (AR) was very low when compared to earlier studies. There was a statistically significant difference between echo diagnosis and clinical diagnosis (p < 0.05). CONCLUSION: It is recommended that echocardiography be done routinely for the diagnosis of cardiac lesions in patients of RHD as clinical examination alone can miss various lesions, especially when the lesions are mild or when multiple lesions are present. PMID- 27407646 TI - Medical Certification of Cause of Death. AB - Medical Certificate of Cause of Death, commonly called Death Certificate, is the most frequently issued certificate, at least by a government employed medical officer, if not by a private practitioner. It is common knowledge that many medical officers, even some of those with incomparable medical knowledge and expertise, do not fill up this document of immense medical and legal importance correctly. The reasons may be many, ranging from ignorance to indifference. Medical officers of Armed Forces Medical Services attending refresher courses (MOJC) have always requested the authors for a class on this topic. Considering these aspects, the authors have tried to clarify different issues concerning the question. PMID- 27407648 TI - Initial Management of Burns. AB - Burns is a preventable tragedy, which is unfortunately still common in India. The possibility of disfigurement, death and emotional trauma as a result of burns is a shattering experience to the victim as well as his/her family. Proper initial management can salvage many such unfortunate victims. Burns patients require close monitoring, barrier nursing and sympathetic attitude of medical and paramedical staff in a burns ICU to have a reasonable chance of survival. PMID- 27407647 TI - Improved Method of Human Excreta Disposal in Field Area. AB - Sanitary disposal of human excreta in field area in semi permanent camps established by the Armed Forces personnel is extremely important to ensure hygiene and sanitation of these camps. The existing method of constructing deep trench latrines (DTLs) has several practical problems. An improved method of constructing DTLs has been evolved, tested and tried by an Infantry Division. This method of human excreta disposal has a greater acceptability among the troops. PMID- 27407649 TI - Ventilatory Strategy in Acute Severe Asthma. PMID- 27407650 TI - Ossification of Posterior Longitudinal Ligament. PMID- 27407651 TI - Dandy-Walker Variant : Prenatal Diagnosis by Ultrasonography. PMID- 27407652 TI - Endoscopic Removal of Ethmoidal Foreign Body. PMID- 27407653 TI - Peculiar Phenomenon in a Case of Calcific Tendinitis of the Shoulder. PMID- 27407654 TI - Metastatic Amelanotic Malignant Melanoma with Unknown Primary - A Case Report. PMID- 27407655 TI - Sudan Black B Positive Acute Lymphocytic Leukemia. PMID- 27407656 TI - Cerebral Venous Sinus Thrombosis : A Great Masquerader. PMID- 27407657 TI - Tropical Pyomyositis with Staphylococcal Scalded Skin Syndrome. PMID- 27407658 TI - Bochdalek Hernia in A Child. PMID- 27407659 TI - Desmoplastic Fibroma : Mandible. PMID- 27407660 TI - Multicystic Dysplastic Kidneys : Antenatal Diagnosis. PMID- 27407661 TI - Heart Failure - Current Concepts. PMID- 27407662 TI - Bed Occupancy Rate. PMID- 27407663 TI - Increase in Incidence of Pterygium in High Altitude Areas. PMID- 27407664 TI - Heart Failure - Current Concepts: Reply. PMID- 27407665 TI - Tackling The Smoking Menace In The Army. PMID- 27407666 TI - Preventive Dentistry : An Achievable Dream. PMID- 27407667 TI - Emergence of New Legal and Ethical Dilemmas in Medical Field. PMID- 27407668 TI - Routine Cyclosporine concentration - C2 level Monitoring. Is it helpful during the early post Transplant Period? AB - BACKGROUND: Pre dose or trough blood cyclosporine (CSA) concentration is routinely monitored and the result is used to alter patient's drug dosing. Patients with identical pre dose blood CSA may have very different systemic exposure to the drug. Recently CSA 2 hour post dose level [C2] has been reported to correlate better with drug exposure. We undertook this study to evaluate the influence of trough and C2, CSA concentration monitoring on short-term renal allograft outcomes. METHODS: 25 patients of renal transplant receiving a triple drug regimen of CSA micro emulsion (Panacea Biotec) 8mg/kg, azathioprine 1mg/kg and prednisolone 0.5mg/kg were analyzed prospectively for graft outcomes. CSA levels were monitored in whole blood by radioimmunoassay using monoclonal antibodies, at 72 hours after the transplant. RESULTS: The mean age of patients was 37.08 + 9.1 years. There were 20 males and 5 females. The mean age of donors was 40.2 + 8.2 years. There were 11 related donors with at least a haplomatch, 4 spousal and 10 unrelated donors with a nil antigen match. The mean pre dose CSA concentration was 289.22 + 171.9ng/ml; range (98.8 + 783.41ng/ml). The CSA concentration at 2 hours after the CSA administration was 838 + 310.87ng/ml (range, 169 + 1268ng/ml). 3 (12%) patients had acute rejection. In these patients the mean pre dose CSA concentration was 328.67ng/ml and the mean C2, CSA concentration was 1006.26ng/ml. CSA induced hemolytic uraemic syndrome was diagnosed in one patient. The trough and C2, CSA concentration levels were 174 and 870.83ng/ml respectively in this patient. CONCLUSION: In our study CSA levels, trough and peak showed significant inter patient variability. The trough and C2 concentration levels did not correlate with the episodes of acute rejection. We conclude that in a triple drug regimen with fixed dosing schedules routine trough CSA level monitoring is not helpful in the acute post renal transplant period. PMID- 27407669 TI - Correlates of Job Satisfaction in Medical Officers. AB - BACKGROUND: A study was carried out to assess the job satisfaction of medical officers of the Armed Forces. METHODS: Medical officers having a minimum of five years service, stationed in a large cantonment having a tertiary care service hospital were administered anonymously the scale developed by Brayfield and Rothe to assess job satisfaction. A total of 64 medical officers (22 administrative cadre, 26 specialists and 16 superspecialists), participated in the study. RESULTS: Overall there was a low level of job satisfaction among the medical officers. There was no significant difference in the level of job satisfaction in the three groups. Only 3 each of administrative cadre and specialist officers were in the higher satisfied group. The most common factor stated (91.5% of the respondents), as contributing towards job satisfaction was an opportunity for self-development. Others in decreasing frequency were job security (51.6%), prestige of organization (38.5%), nature of work (28.8%) and opportunity for promotion (21.6%). Factors for dissatisfaction were poor utilization of skills (80.8%), poor promotional prospects (78.4%), inadequate redressal of grievances (72.7%), organizational policy (68.7%) and inadequate pay and allowances (48.7%). CONCLUSION: It was concluded that job satisfaction is a multi-dimensional phenomenon where it is not easy to assign one factor as the sole determinant of satisfaction/dissatisfaction with the job. PMID- 27407670 TI - Neonatal Immune Thrombocytopenia. AB - BACKGROUND: Neonatal immune thrombocytopenia, a consequence of transplacental transfer of antiplatelet antibodies can result in serious bleeding with disastrous consequences in the otherwise healthy newborn. METHODS: Over 2 years at a service hospital, 5 mothers with chronic autoimmune thrombocytopenia and one with maternal alloimmunisation delivered, which comprised the study sample. RESULTS: Of these, two ladies suffered episodes of thrombocytopenia in the current pregnancy. They were provided platelet transfusions and intravenous immunoglobulins. All patients delivered vaginally. Cord blood platelet was normal in all cases. Three babies developed thrombocytopenia, two due to autoimmune and one alloimmune pathology. The nadir of thrombocytopenia occurred in 36-72 hours with recovery taking place in 10 days. The clinical manifestations were petechiae, ecchymosis, gastric bleed and oozing from vitamin K injection site. Two of the affected babies were provided intravenous immunoglobulins and one steroids. Only one of the two mothers who suffered thrombocytopenia during pregnancy and was provided intravenous immunoglobulins was associated with neonatal thrombocytopenia, an inconsistent relation. It was also observed that antenatally provided immunoglobulins raised effectively maternal rather than fetal platelet counts. However, postnatal immunoglobulins were efficacious in thrombocytopenic neonates. CONCLUSION: Thus inspite of several therapeutic and preventive modalities being described, the optimum management strategy of immune mediated perinatal thrombocytopenia is yet in evolution. PMID- 27407671 TI - von Willebrand Disease : A Clinico-haematological Spectrum. AB - BACKGROUND: Bleeding disorders are commonly seen in clinical practice. von Willebrand Disease (vWD), is the commonest and yet a profoundly under diagnosed cause, having a wide spectrum of clinical presentation. Of its three types, type 1 vWD (70% of the total vWD cases) has the mildest and a highly variable clinical and laboratory presentation. METHODS: A series of ten cases of vWD were comprehensively evaluated using recommended diagnostic parameters and therapeutic interventions. RESULTS: All major types of vWD were represented. A female preponderance, with primary presentation in the form of muco-cutaneous bleeds was observed. A positive history of consanguineous parental marriage and family history of bleeding disorder was elicited in two and three patients respectively. Nine patients were found to be anemic and thrombocytopenia was present in only one. Bleeding time by modified template (SIMPLATE) method, along with activated partial thromboplastin time (APTT) was increased in all ten cases and of these, nine had low factor VIII: C levels. Ristocetin induced platelet aggregation studies were abnormal in all the five cases it was performed. vWF:RCo activity determined in one individual was shown to be low. vWF:Ag assay was done in four cases revealing a near complete absence of von Willebrand factor antigen in one and mildly decreased levels in the other three. vWF multimer assay was advised in three cases. DDAVP, plasma derived vWF, blood products and local antifibrinolytics were used as primary modalities of treatment. CONCLUSION: Thus, strong clinical suspicion, thorough clinical evaluation and judicious use of investigations including repeated investigations at different times are needed for making a diagnosis of vWD. PMID- 27407672 TI - Target Gland Dysfunction Following External Cranial Radiation for Extrasellar Tumours. AB - BACKGROUND: Diseases of the pituitary gland manifest as increased or decreased production of one or more of these hormones that in turn trigger a series of secondary hormonal changes in target glands (Thyroid, Adrenal and Gonad). Dysfunction of target glands may follow treatment with external radiation when hypothalamo-pituitary axis lies within the field of radiation. The present study has been undertaken with the aim to study target gland dysfunction and their relationship with dose of radiotherapy and duration after radiotherapy in patients who have received extracranial radiation for extrasellar tumours. METHODS: In this study, 96 patients who underwent cranial radiation 12 months ago were evaluated. Basal 8 am venous blood samples were taken for estimation of triiodothyronine (T3), thyroxin (T4), thyrotropin stimulating hormone (TSH) and basal cortisol estimation. Pooled samples (three samples taken 20 minutes apart and pooled together) were taken for LH, FSH and testosterone (TE) estimation. Insulin tolerance test was performed for stimulated cortisol levels. RESULTS: Target gland dysfunction was present in 72 (75%) patients. Hypogonadism was present in 48 (53%) of post-pubertal patients. 36% of male patients had hypogonadism whereas 100% of female patients had hypogonadism. Patients with hypogonadism were older, received higher doses of radiation and evaluated earlier after radiotherapy than without hypogonadism. Serum testosterone level declined significantly with increasing doses of radiation. Hypoadrenalism was present in 44 patients (46%). There was no significant difference of age, radiation dose and radiation fraction among patients with or without adrenal insufficiency. Proportion of patients with hypoadrenalism increased with increasing duration after radiotherapy. Hypothyroidism was present in 12 patients (13%). Proportion of patients with hypothyroidism doubled with increasing dose of radiation. Serum T3 level declined significantly with increasing doses of radiation. Patients with hypothyroidism had significantly low T3 and T4 level, but significantly higher TSH and basal and peak cortisol levels than patients without hypothyroidism. CONCLUSION: Target gland dysfunction is common after extracranial radiation for extrasellar tumours. Hypogonadism was the commonest followed by hypoadrenalism and hypothyroidism. Target gland dysfunction was related to age, radiation dose and duration after radiotherapy, but not with fraction of radiation. PMID- 27407673 TI - Circumcision : A Time to Rethink. AB - BACKGROUND: Circumcision is one of the most routinely done surgery world over but has no scientific basis to enforce it on all patients. Of late, the operation has been criticized, non-operative methods have been tried and operations preserving the skin of prepuce have been recommended. The presence of physiological phimosis, which is self-correcting by the age of 15 years in children, needs to be differentiated from the pathological variety. METHOD: The child population reporting to Surgery OPD was taken as sectional representative of the Indian communities and socioeconomic strata. A simple protocol was adapted to differentiate true phimosis from the physiological one and data collected. An observational study was done and data collected for last six years. RESULT: 566 children were referred to the hospital and only 212 were subjected to circumcision. Of these, 169 were cases of true phimosis, 7 had paraphimosis and the rest included 9 ritual circumcisions. CONCLUSION: The incidence in this study is much less as compared to the series from the west. Though rare, this simple surgery is often fraught with complications. A refined approach has been planned for referring cases and selection for surgery thereby reducing unnecessary referrals and circumcisions. PMID- 27407674 TI - Cochlear Implant : Anaesthesia Challenges. AB - BACKGROUND: Cochlear implants are now an acceptable therapeutic option for those patients with irreversible hearing loss and deaf-mutism. The surgery is time consuming and complicated. Hence, the technique of anaesthesia plays a crucial role in success of cochlear implant surgery. Cochlear implant patients have various types of syndromes which are important from anaesthetic as well as surgical point of view. Pre-implant preparation requires objective assessment of hearing, plain X-rays of skull and a CT scan of the temporal bone. Anaesthesia is required for objective assessment of hearing in children under five years of age, to obtain X-rays of skull, magnetic resonance imaging (MRI), CT scan, brain evoked response audiometry (BERA) testing and finally for cochlear implant surgery. Anaesthetic considerations include preoperative familiarisation with the patient and his family. Syndromal illnesses have specific anaesthetic significance such as presence of difficult airway or prolonged QT interval. Parental presence is highly desirable during induction of anaesthesia. Electro surgical instruments especially monopolar ones, should not be used once the cochlear implant is in place. METHODS: In our institution, all cases (15 children) received their cochlear implants under general anaesthesia and formed the study group. Children were administered midazolam orally and inj ketamine during CT scan. Our techniques of general anaesthesia were modified to permit use of nerve stimulators during surgery. To minimise the incidence of vertigo particularly after cochleostomy, postoperative nausea and vomiting, all patients received glycopyrrolate and fentanyl citrate intravenously prior to induction. Other agents used were, thiopentone, suxamethonium and end-tidal 1.3 MAC halothane in 1:2 mixture of oxygen and nitrous oxide (O2 and N2O). Electro diathermy was switched off, before the cochlear device was implanted on the patient. Patients were allowed to breathe spontaneously whenever nerve stimulator was used to locate the facial nerve. Inj Ondansetron 0.1 mg/kg was used as anti emetic agent. Postoperative pain relief was initially provided with fentanyl 1 MUg/kg IV and later with syrup ibuprofen. RESULTS: There were no remarkable anaesthetic or surgical complication in our series except perilymph leakage in two cases. PMID- 27407675 TI - Maxillofacial Injuries in Counter Proxy War Posture of the Armed Forces. AB - BACKGROUND: Various maxillofacial injuries, sustained in counter insurgency operations in the counter proxy war posture (CPWP) of the Armed Forces in the Kashmir valley are being treated at various maxillofacial surgical centres. METHOD: Proper triage, documentation of injuries and mode of injuries along with various clinical, radiological and other investigations were carried out before operating these individuals for primary reconstruction of skeletal tissue and facial soft tissue. RESULT: A total of 324 persons with various types of maxillofacial injuries were treated within the period ranging from 01 January 2000 to 30 June 2002 successfully in this centre as a part of the advanced trauma life support (ATLS) system of Combat Medical Support. CONCLUSION: Proper primary reconstruction (soft tissue and skeletal tissue) of the facial region goes a long way in reducing subsequent disfigurement and morbidity. Improving the structural design of the combat head gear for safety and comfort will go a long way in preventing majority of maxillofacial injuries or can at least reduce the severity of these injuries. PMID- 27407676 TI - Functional Voiding Disorders In Children. PMID- 27407678 TI - Biomedical Waste Management : An Infrastructural Survey of Hospitals. AB - BACKGROUND: The Ministry of Environment & Forests notified the Biomedical Waste (management & handling) Rules, 1998" (BMW Mgt) in July 1998. In accordance with the rules, every hospital generating BMW needs to set up requisite BMW treatment facilities on site or ensure requisite treatment of waste at common treatment facility. No untreated BMW shall be kept stored beyond a period of 48 hours. The cost of construction, operation and maintenance of system for managing BMW represents a significant part of overall budget of a hospital if the BMW rules have to be implemented in their true spirit. Two types of costs are required to be incurred by hospitals for BMW Mgt, internal and external. Internal cost is the cost for segregation, mutilation, disinfection, internal storage and transportation including hidden cost of protective equipment. External costs are off site transportation, treatment and final disposal. METHODS: A study of hospitals was carried out from various sectors like Govt, Private, Charitable institutions etc. to assess the infrastructural requirement for BMW Mgt. Cost was worked out for a hospital where all the infrastructure as per each and every requirement of BMW rules had been implemented and then it was compared with other hospitals where hospitals have made compromises on each stage of BMW Mgt. RESULTS: Capital cost incurred by benchmarked hospital of 1047 beds was Rs.3 lakh 59 thousand excluding cost of incinerator and hospital is incurring Rs. 656/- per day as recurring expenditure. Pune city has common regional facility for BMW final disposal. Facility is charging Rs.20 per kg of infectious waste. As on Dec 2001 there were 400 institutions including nursing homes, labs and blood banks which were registered. CONCLUSION: After analyzing the results of study it was felt that there is an urgent need to standardize the infrastructural requirement so that hospitals following BMW rules strictly do not suffer additional costs. PMID- 27407677 TI - Chronic Urticaria : Expanding the Autoimmune Kaleidoscope. PMID- 27407679 TI - Measuring Template For Thyroplasty. PMID- 27407680 TI - Treatment of Acute Mountain Sickness and High Altitude Pulmonary Oedema. PMID- 27407681 TI - Ezetimibe (Zetia). PMID- 27407682 TI - Retropharyngeal Foreign Body. PMID- 27407683 TI - Management of an Isolated Orbital Blow-out Fracture. PMID- 27407684 TI - The Sural Artery Island Flap in Salvage of a Prosthetic Ankle Joint. PMID- 27407685 TI - Submitral Aneurysm of the Left Ventricle. PMID- 27407686 TI - Malignant Peripheral Nerve Sheath Tumor Presenting as a Massive Intra-abdominal Mass. PMID- 27407687 TI - Delayed Endoscopic Retrieval Of Retained Bullet in the Urethra. PMID- 27407688 TI - Palato-pharyngeal Approach to the Parapharyngeal Space. PMID- 27407689 TI - Carcinosarcoma of the Breast With An Unusual Secretory Carcinoma as the Carcinomatous Component. PMID- 27407690 TI - WAR SURGERY: Reply. PMID- 27407691 TI - WAR SURGERY. PMID- 27407692 TI - Carrier Rate of B-haemolytic Streptococcal Throat Infection : Understanding Potential For Prevention. PMID- 27407693 TI - Iatrogenic Disorders. PMID- 27407694 TI - Training and Credentialing in Laparoscopic Surgery - The Need of the Day. PMID- 27407695 TI - Pulmonary Hydatid : Diagnosis and Response to Hypertonic Saline Irrigation and Albendazole. AB - BACKGROUND: Pulmonary hydatid is caused by larval stage of parasite Echinococcus granulosus. Although surgery still remains the definitive therapy, various workers have tried albendazole and sterilization of cysts with varying result. METHODS: 32 patients(21 males, 11 females) of pulmonary hydatid disease with average age 32.5 years(21-51 years) treated by us between Jan 97 to Apr 2001 were analysed. Diagnosis was established clinically, radiologically and by serological testing. 16 patients who had simple cyst were treated with 20 ml percutaneous hypertonic(20%) saline irrigation of the cyst along with albendazole (400 mg twice a day, 6 cycles of 4 weeks with 2 weeks drug free period between the cycles). 13 patients of complicated cysts were treated with 6 cycles of albendazole. All cases were followed up for one year. 16 patients including three fresh cases were subjected to surgical resection. RESULTS: Pleural involvement was noted in 10 patients. On chest radiography 19 patients had homogenous oval or circular cysts, 6 patients had crescent sign and 10 had water lily sign. After percutaneous hypertonic saline irrigation all patients showed initial regression in size and developed complicated cysts with water lily sign but subsequently there was no regression. Of 13 patients treated with albendazole, 3 patients showed complete resolution and 2 patients showed regression of cyst. All these 5 patients had shown regression during first cycle of albendazole. 16 patients were subjected to surgery (6 after saline irrigation, 7 after albendazole course and 3 fresh cases). No difference was noted in these groups on histopathological examination. CONCLUSION: From this study it was evident that those patients who demonstrate regression in size during first cycle of albendazole are likely to benefit and improve with further cycles of it. Those who do not respond should be subjected to surgery. Result of percutaneous hypertonicsaline irrigation as scolicidal was not encouraging. PMID- 27407696 TI - Childhood Bacterial Meningitis and Usefulness of C-reactive Protein. AB - BACKGROUND: C-reactive protein raises rapidly in the first 24-48 hours of occurrence of bacterial meningitis and in large incremental increases thereafter. This prospective study was undertaken in a tertiary care hospital of Armed Forces to ascertain the usefulness of C-reactive protein in early diagnosis of bacterial meningitis. METHODS: All children admitted during the period of study, with clinical suspicion of meningitis were clinically, biochemically, cytologically and bacteriologically investigated to clinch the diagnosis. Blood and CSF were also sent for C-reactive protein assay by latex agglutination test. CSF gram staining, culture and biochemical results were taken as gold standard. CSF and serum CRP were then evaluated against this gold standard. Statistical analysis was done by Epiinfo 6. RESULTS: There were 63 cases of meningitis admitted in the hospital. By gold standard, there were 38 cases of bacterial, 21 cases of tubercular and 4 cases of viral meningitis. H. influenza was the predominant organism grown. CSF C-reactive protein was raised in 33 cases of bacterial and 2 cases of tubercular meningitis. Serum C-reactive protein was raised in 29 cases of bacterial, and eight cases of tubercular meningitis. These tests were negative in all cases of viral meningitis. The sensitivity and specificity of serum and CSF C-reactive protein was 96% and 100%. CONCLUSION: Quantitative and qualitative assay of C-reactive protein is a simple bedside test. It can be completed in 10 minutes and requires only 0.2 ml of blood. This will significantly reduce unnecessary antibiotics to children. PMID- 27407697 TI - Outbreak of Pneumococcal Pneumonia among Military Recruits. AB - BACKGROUND: Between 04 Mar 2002 to 21 Mar 2002, 31 cases of pneumonia were admitted at a military hospital in South India. Most of these cases were young recruits. The out break was investigated to ascertain the cause and suggest preventive measures. METHODS: Detailed epidemiological history was taken from all 31 cases and 100 controls. Case sheets, laboratory reports and chest radiographs were studied. Laboratory investigations included sputum examination by Gram stain and blood cultures on brain heart infusion broth. Cultures grown on liquid media were subcultured on solid media. The regimental centre was visited to note the living and environmental conditions. RESULTS: Epidemiological investigations revealed overcrowding in the regimental centre. The space per recruit was below recommended standards. 51.6% of recruits who contacted pneumonia were sleeping on double deckers as compared to 21% of healthy controls. Blood culture was positive for Streptococcus pneumoniae in 25.8% of the cases. Chest radiograph showed consolidation typical of lobar pneumonia in 67% of the cases. CONCLUSION: The outbreak of pneumococcal pneumonia occurred due to overcrowding. Chilly weather conditions and stress were contributing factors. PMID- 27407698 TI - Local Anaesthesia for Fiberoptic Intubation : A Comparison of Three Techniques. AB - BACKGROUND: The successful conduct of fiberoptic aided intubation is dependent upon effective local anaesthesia. The aim of the study was to compare three different methods of anaesthetizing the airway. METHODS: 60 adult patients (American Society of Anaesthesiologists status I-III and Mallampati class III & IV), scheduled for elective surgery, received sedation followed by spraying of the nares and posterior pharyngeal wall with 4% lignocaine. Thereafter the patients received 4 ml of 4% lignocaine either by transtracheal injection (n=20, group A), via intubating fiberscope (Pentax F1-10P2) using 'spray as you go' technique (n=20, group B) or by nebulizer (Devilbiss 5610W) 20 min before intubation, (n=20, group C). Patients were asked to score the procedure using visual analog scale (VAS) and severity scores. Episodes of coughing, choking, stridor, extra / total local anaesthetic used and intubation times were recorded. Patients were monitored continuously for vital parameters. RESULTS: Group B patients showed better VAS scores with shorter intubation times and had a lower incidence of coughing and choking. The endoscopists' VAS scores also showed a preference for group B. CONCLUSION: In conclusion the 'spray as you go' technique was safe, provided effective local anaesthesia and was preferred by both patients and endoscopists. PMID- 27407699 TI - Effects of BCG Vaccination on Evolution of Leprosy. AB - BACKGROUND: BCG vaccine is considered to have immunoprophylactic potential in leprosy. However controversy exists about the extent of prophylaxis it provides. In view of this, a study was undertaken to see the evolution of disease in established cases of leprosy who were already vaccinated with BCG and to compare it with the cases of leprosy who were not vaccinated with BCG. METHODS: 114 newly diagnosed cases of leprosy were studied. Patients were divided into two groups BCG vaccinated and non-vaccinated. Clinical diagnosis of leprosy was confirmed by bacteriological and histopathological studies in each case. All patients were given standard anti leprosy treatment and were evaluated monthly for a minimum period of one year. RESULTS: All the cases were males in the age group of 20 to 50 years. 25.4% of cases had received BCG vaccine and 74.6% were not vaccinated for the same. No significant difference was observed in the incidence of different types of leprosy in vaccinated and non-vaccinated groups. 25.9% cases in non-vaccinated group developed lepra reaction as compared to 13.8% in vaccinated group. The incidence of deformities and disabilities in vaccinated group was only 10.3% as against 18.8% in non-vaccinated group. The rate of bacillary clearance appeared faster in vaccinated group. CONCLUSIONS: Although there is no significant difference in the pattern of different types of leprosy in BCG vaccinated and non-vaccinated cases, there is reduction in the incidence of reactions as well as deformities and disabilities in BCG vaccinated cases as compared to non-vaccinated cases. PMID- 27407700 TI - Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis. AB - BACKGROUND: The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis. METHODS: 24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months. RESULTS: 10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis. CONCLUSION: Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs. PMID- 27407701 TI - Total Hip Replacement in Avascular Necrosis of Femoral Head. AB - BACKGROUND: A study was conducted to evaluate the role of total hip replacement in cases of advanced avascular necrosis of the head of femur in patients admitted to two tertiary care military hospitals. 20 patients reporting with avascular necrosis of femoral head were taken for study. METHODS: Out of 20 patients, 16 were males and 4 were females. In 7 cases there was history of chronic alcohol intake and among them one patient was on steroids for long time for the treatment of bronchial asthma. 2 patients developed avascular necrosis of the femoral head following pregnancy and in two cases, it was post-traumatic. In the remaining nine cases, no cause was found and were so considered idiopathic. They were evaluated pre-operatively and total hip replacement was done in all twenty cases. RESULTS: Patients were evaluated using Harris hip score. There was improvement of the score in all cases. CONCLUSION: Total hip replacement is a boon for patients of advanced avascular necrosis of femoral head. PMID- 27407702 TI - Reconstruction of Cranial Defects in Armed Forces Personnel - Our Experience. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of heat cured 'poly methyl methacrylate resin prosthesis and to assess the acceptability of the indigenously manufactured titanium mini bone plate and screws in patients treated for repair of cranial defects. METHODS: 17 patients with cranial defect were treated for reconstruction of the skull defect with two types of implants i.e. Acrylic resin plate prosthesis and titanium minibone plates, either in combination or singularly. In these cases, the skull defects resulted from trauma (88.23%) or due to ablative tumour surgery (11.96%). Acrylic implant was used in 12 cases (70.85%), titanium plates and screws in 2 cases (11.76%) and a combination of both of the above in 3 cases (17.64). RESULTS: The primary reconstruction was carried out in 2 cases (11.96%) and secondary reconstruction was done in 15 cases (88.23%). Majority of the cases underwent secondary reconstruction because of the initial surgical emergency requiring quick debulking and closure. In 2 cases where primary reconstruction was done, the second surgery could be avoided with gratifying results. CONCLUSION: 70.85% underwent reconstruction with polymethyl methacrylate resin prosthesis and in the rest either titanium plates were used singly or in combination. Only in one patient, there was rejection of the implant due to infection. In 94% cases the graft was well taken up with excellent results. PMID- 27407703 TI - Nutritional Support In The Critically Ill Child. PMID- 27407704 TI - Embracing a Revolution - Telemedicine. AB - The recent advances in information and communication technologies offer real and practical opportunities to health professionals to share expertise and resources in health care over distances. For a country like India with pockets of medical excellence surrounded by a vast number of badly equipped hospitals with limited specialists, telemedicine could revolutionize health care. The potential of telemedicine seem to be vital in avoiding the frame of travel, in timely getting specialist advise to remote areas, minimizing the cost and of course an opportunity to learn from each other. In developed countries the technological advancement and research aims primarily to satiate the needs of their armed forces and to ensure tactical and technical supremacy. The medical community in the Indian Armed Forces should harness the technologies and embrace this revolution of the information age to provide world class combat casualty care. PMID- 27407705 TI - Cardiac MRI in Congenital Heart Disease - Our Experience. AB - A significant recent advance that has occurred world over in the continuously evolving field of Magnetic Resonance Imaging (MRI) practice is the introduction of Cardiac applications. Cardiac MRI has moved to the centre stage of clinical management strategy by non-invasively imaging the structure as well as function of the heart. It has a wide range of specific applications such as delineation of morphological anatomy, quantification of flow and pressure across cardiac valve dysfunction, evaluation of myocardial function, assessment of infarcts, mapping coronary arteries and so on. Evaluation of congenital heart disease (CHD) is an important application of Cardiac MRI since the morphological details of chambers, septum, defects and anomalous connections are depicted accurately. Besides, flow information across valves, chambers, outflow tracts and shunts are also provided. This article describes our experience in the use of cardiac MRI in congenital heart disease. PMID- 27407706 TI - Techniques in Cardiology : PDA Closure in Children. AB - BACKGROUND: Transcatheter closure of patent ductus arteriosus (PDA) with various devices has been evaluated worldwide and in selected cases can be performed successfully, thus avoiding the morbidity associated with surgical closure. METHODS AND RESULTS: A 2 year old female child presented with PDA and aortic angiography showed large PDA (tubular). This defect can be closed nonsurgically by coils and devices. The coil used are normally 0.038" having delivery system called Flipper, but this child had a large PDA and so was closed by thicker coil 0.052" using a coil-Bioptome-sheath system, which is the first reported case from the Armed Forces. CONCLUSIONS: We report the initial experience at our center of closure of PDA with a new coil-Bioptome-sheath system. PMID- 27407707 TI - Acute Abdomen in Gynaecological Practice. AB - Acute abdomen in pregnancy is due to consequence of pregnancy itself or is totally unrelated to pregnancy. During pregnancy, a woman is at an increased risk of acute abdomen due to various physiological changes. The article discusses the various conditions which can present as acute abdomen in women during pregnancy and in non-pregnant state. The clinician often has a difficult task in diagnosing and managing acute abdomen in pregnancy. Clinical evaluation is further confounded by various anatomical and physiological changes occurring in pregnancy. The growing gravid uterus too causes difficulty in detailed examination. The general reluctance to use conventional X-rays because of pregnancy should be set aside when faced with a seriously ill mother. A reluctance to operate during pregnancy adds unnecessary delay, which increases morbidity for both the mother and the fetus. Adnexal accidents should always be kept in mind in a woman with acute abdomen even if she is not pregnant. Such mistakes should be avoided as prompt diagnosis and appropriate therapy are crucial. A general approach to acute abdominal conditions in pregnancy is to manage these problems considering the risk to mother regardless of the pregnancy. PMID- 27407708 TI - Wegener's Granulomatosis with Fungal Lung Infection in a Child. PMID- 27407709 TI - Preoperative Parathyroid Radionuclide Scintigraphy in Hyperparathyroidism. PMID- 27407710 TI - Mercury Toxicity - A Case Report. PMID- 27407711 TI - Anaesthetic Management of Congenital Lobar Emphysema : A Report of Two Cases. PMID- 27407712 TI - Ileocaecal Endometriosis with Intestinal Obstruction. PMID- 27407713 TI - Signet Ring Carcinoma of the Breast : An Uncommon Type of Breast Carcinoma. PMID- 27407714 TI - Osteoma of the Mastoid Bone - A Case Report. PMID- 27407715 TI - Langerhans' Cell Histiocytosis - Case Report. PMID- 27407716 TI - The Revaccination of Ty 21a. PMID- 27407717 TI - The Revaccination of Ty 21a: Reply. PMID- 27407718 TI - Treatment of Casualties in a Forward Hospital of Indian Army: Nine Years Experience: Reply. PMID- 27407719 TI - Treatment of Casualties in a Forward Hospital of Indian Army: Nine Years Experience. PMID- 27407720 TI - History Taking in Clinical Medicine - A Forgotten Art? PMID- 27407721 TI - JNC VII Creates a New "Prehypertensive" Category. PMID- 27407722 TI - Emotional First Aid - Critical Incident Stress Management. PMID- 27407723 TI - JNC VII Creates a New "Prehypertensive" Category: Reply 2. PMID- 27407724 TI - History Taking in Clinical Medicine - A Forgotten Art?: Reply 1. PMID- 27407725 TI - Arthroscopy : No More Such a Limited Procedure. PMID- 27407726 TI - Arthroscopy : No More Such a Limited Procedure: Reply. PMID- 27407727 TI - What is New in Acute Pancreatitis? PMID- 27407728 TI - Recent Advances in Diagnosis of Cancer. PMID- 27407729 TI - Is Patient's Preference for Medical Care Changing? AB - BACKGROUND: An assorted group of 1000 army personnel below officer's rank was surveyed to find out its preference for medical set up between that of the Armed Forces and the civil. METHODS: Survey for preference of medical treatment was done based on a structured questionnaire. The sample was taken from different states of India covering the entire nation. RESULTS: 65% of the surveyed personnel preferred the Armed Forces medical set up to that of the civil. Yet 35% is a big number going for civil medical set up. About half of the above would choose alternative therapy like homeopathy and ayurveda. CONCLUSION: Two issues come to notice. Whether there is any scope for introducing popular alternative therapy in the Armed Forces and does an improvement in the existing medical set up in the Armed Forces change the preference of the clients? PMID- 27407730 TI - Cannabis Use in Psychiatrie Patients. AB - BACKGROUND: Cannabis abuse has been associated with psychiatric disorders. METHODS: The pattern of cannabis use and incidence of cannabis dependence and cannabis psychosis among 471 consecutive patients admitted to a tertiary care psychiatric center was investigated. RESULTS: Cannabis use was reported by 67 (14.23%) patients of whom 42 (8.92%) were occasional users, 18 (3.82%) were classified as frequent users while 7 (1.49%) fulfilled criteria for cannabis dependence. 3 (0.64%) patients showed symptoms which were characteristic of cannabis psychosis. Among the 67 cannabis users, 56 (83.58%) had their first exposure to cannabis before entering service at 13-19 years of age. The remaining 14 (16.09%) began consuming cannabis 1-5 years after joining service. CONCLUSION: The reasons given for using cannabis were curiosity about its effects 32 (47.76%), peer pressure 17 (25.37%) or traditional use during festivals 18 (26.87%). PMID- 27407731 TI - Inappropriate Use of Hospital Beds in a Tertiary Care Service Hospital. AB - BACKGROUND: The cost of medical care is continuing to rise and cost containment measures need to focus on inappropriate hospitalization. Armed Forces Medical Services ensure universal access to its consumers but continuous increase in patient load is stretching the capability of service hospitals. The present study was undertaken to determine the rate of inappropriate hospitalization in a large tertiary care service hospital. METHODS: Appropriateness Evaluation Protocol (AEP) was used to assess the appropriateness of hospital days, the study being carried out in the acute medical and acute surgical wards of the hospital on randomly selected days over a period of three months. RESULTS: Inappropriate patient days were found to be 29.48% during the study period, with 34% of acute surgical patient days and 24.4% of acute medical patient days found to be inappropriate. No statistically significant difference was observed in the rate of inappropriate hospital stay between serving personnel and ex-servicemen. 31.25% non local patients as compared to 25.81% of local patients were found to have inappropriate hospital stays, though the difference was not found to be statistically significant. 60.71% of inappropriate stays were found in the initial period of admission (1-5 days), the phenomenon being observed both in the acute surgical and acute medical wards. CONCLUSION: The study shows that the rate of inappropriate patient days is quite high among the study population and regular utilization reviews need to be carried out to conserve health care resources available with the service hospitals. PMID- 27407732 TI - Study of p53 and bcl-2 Oncoproteins in Ulcerative Colitis with Dysplasia. AB - BACKGROUND: Dysplasia in ulcerative colitis has been graded on haematoxylin and eosin stain using Riddle's criteria. This system was formed to nullify the inter observer variation. Few cases of early dysplasia were missed when purely screened on morphology. This study was carried out to detect early dysplasia using p53 and bcl-2 oncoproteins. METHODS: A retrospective study was carried out on paraffin blocks of 100 histologically diagnosed cases of ulcerative colitis at a large service hospital. Haematoxylin and Eosin stained (H &E) slides of these cases were re-examined as per standard techniques. RESULTS: On correlating histological grades with p53 immunoscore it was found that 90.76% of cases graded as negative for dysplasia on H & E, got an immunoscore of 0 and other 9.24% cases which were graded as negative for dysplasia got a score 1+. This shows that the immunohistochemistry was able to pick up 6 cases, which were missed by routine histology. Nine out of 11 cases in which the pathologists could not rule out a dysplasia and graded them as indefinite (probably negative for dysplasia) got a score of 0. In these cases possibly the histological features may be construed as an acute inflammation or repair induced dysplasia which were suspicious for neoplastic dysplasia on routine histology sections. On analyzing our findings on bcl-2 immunohistochemistry it was seen that there was no significant concordance (p>0.05) of immunoscore with the grades of dysplasia estimated morphologically. CONCLUSION: Our study recommends that p53 should be used as regular immunohistochemical marker while grading the dysplasia of ulcerative colitis, especially in indefinite cases as it brings objectivity in grading. Our study also came to a conclusion that use of bcl-2 for grading dysplasia of ulcerative colitis is not of any significant help. PMID- 27407733 TI - Psychosocial Variables of Voluntary Blood Donors at Blood Bank of a Medical College. AB - BACKGROUND: This study was undertaken to study the motivational factors leading to voluntary blood donation and understanding the psychosocial variables of blood donors. METHODS: 300 blood donors were selected by systematic random sampling method. RESULT: It was observed that most of the voluntary donors were males (89.3%) and belonged to age group 16-25 years (48%). Most of the donors (93.46%) had studied upto high school and above and 84.33% of the donors belonged to the middle class. 27% of the donors had donated blood previously. The common motivational factors to donate blood were for 'a good cause', 'for the society' and 'to save a life'. 4.67% of them donated blood for self satisfaction. CONCLUSION: Motivation, recruitment and retention of voluntary blood donors are important criteria to achieve safe blood donation. PMID- 27407734 TI - Three Dimensional Spiral CT Imaging of the Musculoskeletal System: Application and Advantages. AB - BACKGROUND: Clinical applications of spiral computed tomography (CT) have increased extensively over the past decade and continue to widen rapidly. The introduction of three-dimensional(3-D) reconstruction in CT technology has revolutionized medical imaging. This advancement has been possible due to the combination of spiral computed tomography and various 3-D reconstruction protocols which have permitted rapid and comprehensive examination of all regions of the body. It has unequivocal advantages in the preoperative planning of craniofacial surgery, assessment of complex fractures of the skeletal system especially pelvis and in the surgical treatment of dysplastic hips in children. METHODS: 3-D spiral CT imaging of various parts of the musculoskeletal system was carried out in 60 cases using available protocols, at the CT scan center of a large tertiary care service hospital. RESULTS: The study provided a new approach in the analysis of complex anatomic relationships of the musculoskeletal system. Therapeutic planning whether surgical or medical was to a great extent aided by the anatomic information available from these images. CONCLUSION: 3-D CT imaging is a rapid, non-invasive and accurate technique for diagnosis, pre-operative evaluation as well as post-operative assessment of a large number of musculoskeletal diseases. 3-D CT studies have come to stay and with continued improvement in CT technology it has now become an integral part of imaging studies of the musculoskeletal system. PMID- 27407735 TI - Phacotrabeculectomy Versus Conventional Combined Technique in Coexisting Glaucoma and Cataract. AB - BACKGROUND: To evaluate and compare efficacy and outcome after single site phacotrabeculectomy and conventional combined surgery in cases of coexisting primary open angle glaucoma and cataract. METHODS: This prospective study on fifty patients of concurrent primary open angle glaucoma and cataract, who had undergone combined surgery as single site phacotrabeculectomy or conventional single site trabeculectomy with extracapsular lens extraction with IOL implantation in 25 cases each. Evaluation was based on operative and postoperative complications, control of IOP and visual outcome. The follow up period ranged between twelve months to eighteen months. RESULTS: The mean medically controlled preoperative intraocular pressure was 22 mm of Hg (Range 18 to 35 mm of Hg) by applanation method of tonometry. The range of postoperative intra-ocular pressure after one year was 11 to 22 mm of Hg in first and 14 to 26 mm Hg in second group. Failure to maintain optimum postoperative IOP without Beta blocker was more frequent after conventional combined procedure. There was no significant difference in incidence and pattern of postoperative complications. CONCLUSION: Phacotrabeculectomy provides effective and sustained visual recovery and adequate control of intraocular pressure as compare to conventional combined procedure. PMID- 27407736 TI - Mine Blast Injuries - Our Experience. AB - BACKGROUND: The sudden increase in incidence and magnitude of mine blast injuries prompted us to highlight the problem and its management. METHODS: The cases of mine blast injuries occurring during mining and demining in a particular geographical area were analysed. Total 27 cases of mine blast injuries occurred during mining or demining operations in a period of 13 months. RESULTS: Various body regions were involved in the mine blast injuries but the main brunt was borne by feet and legs followed by multiple body regions due to splinters. 14 patients underwent below knee (BK) amputation while 4 patients required through knee (TK) amputations. The effect of blast was so severe that most of the cases required 2 to 5 times wound debridements. The initial aggressive debridement / open stump amputation saved the limb and life of all patients. CONCLUSION: A mine blast causes extensive injuries and psychological trauma. Management is needed urgently, surgery is difficult, and amputation is often inevitable. Maximum lives and limbs can be saved with aggressive debridement, repeated inspections and dressings under anaesthesia and definitive closure at optimum time. PMID- 27407737 TI - Outbreak of Multi-drug Resistant Salmonella Typhi Enteric Fever in Mumbai Garrison. AB - BACKGROUND: There was an epidemic of enteric fever in Mumbai garrison during Nov Dec 2000 with more than 150 cases admitted to a tertiary care service hospital. METHODS: All the cases presented with fever and some had splenomegaly, bradycardia, abdominal pain and diarrhoea. The epidemic was investigated by the station health organization (SHO) and the case and bacteriological study was carried out in pathology laboratory of the service hospital. The serological study was carried out at Armed Forces Medical College (AFMC), Pune and the Phage typing was carried out at Lady Harding Medical College, New Delhi. RESULTS: Blood cultures were positive in 92(63%) for Salmonella typhi and Widal test was positive in 83(55%). All strains were resistant to four primary drugs i.e. ampicillin, chloramphenicol, co-trimoxazole and tetracycline. All but two were treated successfully with ceftriaxone. The Salmonella typhi belonged to phage group E1 and biotype I. CONCLUSION: Extensive epidemiological investigation of cases and water sources of cantonment area pointed to a common source of the epidemic i.e. the well near 'Gurudwara'. PMID- 27407738 TI - Termination of Pregnancy in First Trimester - Medical Option. AB - BACKGROUND: The objective of this study was to confirm the effectiveness and safety of methotrexate and misoprostol or misoprostol alone for abortion up to 12 weeks of gestation. METHODS: A group of volunteer patients desiring MTP with gestations up to 84 days (12 weeks) were studied. The patients were divided into 2 groups. Group 1 patients with gestation up to 56 days were further subdivided as (a) Patients who received methotrexate 50 mg IM + misoprostol 800 gms intravaginal and (b) patients who only received 800 gms of misoprostol. Group 2 included the patients who were 8-12 weeks pregnant and they received same treatment as group 1 (b). Outcome measures assessed included successful abortion (complete abortion without need for surgery), side effects, decrease in hemoglobin and mean duration of vaginal bleeding. RESULTS: Complete abortion occurred in 36 (90%) of 40 patients in group 1 (a), 10 (67%) of 15 patients in group 1(b) and 29 (83%) of 35 patients in group 2. There were only 2 patients with clinically significant decrease in hemoglobin, but none required transfusions. Vaginal bleeding lasted 15 +/- 6 days in group 1 (a), 16 +/- 6 days in group 1(b) and 16 +/- 5 days in group 2. All the patients stopped bleeding when endometrial thickness was < 5mm. Five percent women had stomatitis after methotrexate and 44% patients had fever with chills after misoprostol administration. CONCLUSION: Considering the low cost and availability of methotrexate and misoprostol, these drugs constitute a good alternative for medical abortion. They are safe and effective. PMID- 27407739 TI - Introduction of Modern Stretchers in Armed Forces for Improving Casualty Evacuation in Field with Special Reference to Casualty Evacuation in Mountains. AB - Indian Army has two service stretchers, the Stretcher Folding Light Weight and the Ambulance Stretcher Mark II. Few Imported stretchers have limited distribution. Units also improvise stretchers. Troops deployed in the forward areas deserve better stretchers to facilitate casualty evacuation especially in mountains. Modern stretchers suitable for the Indian Armed Forces have been described. If provisioned, they will improve the efficacy of combat survival, and combat medical support in the field, especially in mountains. PMID- 27407740 TI - Skin and Psyche : Diversionary Symbiosis. AB - A significant proportion of patients with skin diseases have associated psychosocial factors. Not only does psychopathology manifest on the skin in absence of any real skin disease, primary skin disorders can also be exacerbated by emotional stress adversely influencing the homeostasis of immunological and inflammatory processes in deeper layers of the skin. Furthermore, many patients develop emotional problems as a result of having disfiguring skin diseases. In addition, some patients having solely sensory disturbances in absence of primary dermatoses or identifiable medical or neurological conditions, as well as some purely dermatologic conditions such as post-herpetic neuralgia may preferentially need psychotherapeutic modalities to address their underlying psychopathology irrespective of the presenting dermatologic manifestation arising out of 'somatisation' of a psychopathology into physical problems. The most obvious course of action of referral to a psychiatrist or another mental health professional may unfortunately not be readily tenable either due to the perceived stigma associated with psychiatric illness or lack of insight on the part of patients. In the interregnum, effective management of the psychologic or/and psychiatric problems can only be done by the dermatologist provided he has an adequate knowledge base and experience to undertake psychotherapeutic modalities. PMID- 27407741 TI - Avian Flu - A Bird's Eye View. AB - Influenza A (H5N1) virus infects a variety of animals, birds and humans. Present ongoing epidemic of this deadly virus in poultry livestock and humans has had major economic and health repercussions. It causes a wide spectrum of clinical features in human beings ranging from mild respiratory tract infection to a fatal pneumonia leading to multi organ system failure. Diagnosis is mainly clinical, aided by lab features like lymphopaenia and non-specific chest X-ray findings. Diagnostic tests are being evolved for rapid and specific diagnosis. Management is mainly symptomatic. Newer and effective antivirals, i.e. amantadine, zanamivir etc are also being tried. PMID- 27407742 TI - Bonded Pendulum Appliance. AB - Orthodontic therapies involving no compliance from patients are the mainstay of modern orthodontics. Class II division 1 malocclusions constitute the bulk of cases requiring extractions to facilitate space gain to correct it. The Pendulum Appliance is an effective and reliable method for distalizing maxillary molars. Its major advantages are minimal dependence on patient compliance, ease of fabrication, one-time activation, adjustment of the springs if necessary to correct minor transverse and vertical molar positions and patient-acceptance. Simple laboratory procedure for fabrication and relatively low cost make it an excellent appliance to be incorporated into regular practice. PMID- 27407743 TI - Status Epilepticus in Children. AB - Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure and identification of etiology. It results from an inability to normally abort an isolated seizure either due to ineffective inhibition, or due to abnormally persistent excessive excitation. Symptomatic SE is more common in younger children and the likely etiology depends on the age of the child. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. Benzodiapenes, phenytoin and phenobarbital form the mainstay of treatment. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Patient education and home management of seizures is important to reduce the morbidity and mortality associated with SE. PMID- 27407744 TI - Arterio-enteric Fistula - An Unusual Complication of Improper Wound Closure. PMID- 27407745 TI - Post-traumatic Massive Abdominal Wall Defect- A Challenge. PMID- 27407746 TI - Facial Nerve Neuroma : A Case Report. PMID- 27407747 TI - Epidural Abscess and Discitis Following Spinal Anaesthesia- A Case Report. PMID- 27407748 TI - Unusual Case of Carpometacarpal Dislocation of All the Four Fingers of Ulnar Side of Hand. PMID- 27407749 TI - The First Allogeneic Bone Marrow Transplantation in the Armed Forces for Thalassemia. PMID- 27407750 TI - Spontaneous Pneumomediastinum in an Adolescent. PMID- 27407751 TI - Immunosuppressives in Peripheral Ulcerative Keratitis. PMID- 27407752 TI - Coexisting Tuberculosis And Mucinous Carcinoma Of Caecum - A Case Report. PMID- 27407753 TI - A Case of Giant Hairy Pigmented Nevus of Face. PMID- 27407754 TI - Psychiatric Intervention in Amputees: Reply. PMID- 27407755 TI - Psychiatric Intervention in Amputees. PMID- 27407756 TI - One Man HAPO Bag: Reply. PMID- 27407757 TI - One Man HAPO Bag. PMID- 27407758 TI - Neonatal Humerus Shaft Fracture Appropriate Treatment Method. PMID- 27407759 TI - External Cephalic Version : An Old Art With New Relevance. PMID- 27407760 TI - Neonatal Humerus Shaft Fracture Appropriate Treatment Method: Reply. PMID- 27407761 TI - Maternal Mortality - Indian Scenario. PMID- 27407762 TI - Maternal and Neonatal Factors Adversely Affecting Breastfeeding in the Perinatal Period. AB - BACKGROUND: Despite its known advantages, breastfeeding rates are low world over. Large number of factors affect breastfeeding. This study was designed to detect maternal and neonatal factors that adversely affect breastfeeding in the perinatal period. METHODS: A prospective, single-blinded study was conducted on randomly chosen mother-infant pairs in the maternity ward of a tertiary care service hospital. Only full term singletons born by normal vaginal delivery were studied. The B.R.E.A.S.T observation score and time spent by the infant at the mother's breast were primary outcome variables. Maternal age, gravida, para status and education level were recorded. Birth weight, sex, gestation age of the infant and time interval from birth to observation were also recorded. Initial univariate analysis followed by multivariate analysis was performed using SPSS ver 7.5 software. RESULTS: A total of 54 mother-infant pairs formed the study group; 19(35.2%) were primigravidas. Primigravidas status of the mother led to significantly lower scores (p<0.04; 95% CI 0.10 to 3.62) as did maternal age < 26 years (p<0.04; 95% CI 0.2. to 3.46) on univariate analysis. Low birth weight (<2500 g) was the only neonatal factor that significantly lowered breastfeeding scores (p<0.02;95%Cl 0.56 to 6.31). On multivariate analysis only primigravida status was significantly associated with lower scores (p<0.02). The alpha value of the study was 5% and the power was 74%. Time spent by infant on breast was not significantly different between primigravida and non-primigravida mothers. CONCLUSION: Primigravida status adversely affects breastfeeding scores; therefore counseling and support should be focused on this group. Extra care should also be taken to ensure adequate breastfeeding by younger mothers and in those with low birth weight infants. Larger studies with long-term follow up will be able to identify other factors and dertermine the effects of focused counseling and support in the perinatal period upon long-term breastfeeding rates. PMID- 27407763 TI - Mode of Detection of HIV Infection - A Retrospective Study of 612 Cases. AB - BACKGROUND: Trends in mode of detection of HIV infection in the Armed Forces required to be analyzed to formulate future strategies for early detection. METHODS: A retrospective study was thus conducted in 612 newly diagnosed HIV positive cases between January 1997 to August 2002. RESULTS: 182(29.74%) patients had already developed Category C conditions when detected to be HIV-positive, 176(96.70%) with mycobacterial disease, majority (67.61%) of them being pulmonary tuberculosis, followed by recurrent bacterial pneumonia in 3 (1.65%), pneumocystis carinii pneumonia (PCP) in 2(1.1%) and oesophageal candidiasis in one (0.55%). Herpes zoster was the third most common mode of detection accounting for 86 (14.05%) of the cases (24.6% of them with involvement of ophthalmic branch of trigeminal nerve), after tuberculosis in 176(28.76%) and blood donors in 98(16.01%), followed by constitutional symptoms in 59(9.64%) cases, investigation for STDs in 56(9.15%), bacterial pneumonia in 6(0.98%) and oral mucosal candidiasis in only one (0.16%) case. None was detected during acute retroviral illness and only 5(0.82%) cases were detected while being investigated for generalized lymphadenopathy. Amongst the cases detected during investigation for STDs, majority (26.79%) were on STD surveillance. 22(3.60%) cases tested positive when their spouses were detected to be HIV-positive, 20(3.27%) while being screened for surgery, 4(0.65%) for posting abroad and 2(0.32%) each during investigation when child was found HIV-positive and investigation for HBV infection. Remaining 69(11.27%) patients were detected during investigation of various related or unrelated conditions including one (0.16%), which reported voluntarily after a high-risk exposure. CONCLUSION: There is a need to encourage voluntary reporting and identify more number of cases during acute retroviral syndrome and PGL stage. PMID- 27407764 TI - Fluoroscopic Guided Fallopian Tube Recanalisation. AB - BACKGROUND: Fluoroscopic fallopian tube recanalisation is a procedure that relieves proximal fallopian tube obstruction with minimal trauma. Commercially available fallopian tube catheterization sets are costly and cumbersome to use. The modified technique used is easy, less traumatic and lessens the procedure and fluoroscopy time. MATERIAL AND METHODS: A headhunter catheter cut 40cm from its tip was introduced into the uterus under direct vision over a 0.035" guide wire. A 50-cm headhunter 3F catheter was passed through tubal ostium. Microguide wire 0.018" (Terumo) was passed into the fallopian tube. On successful recanalisation free peritoneal spill was seen in the peritoneum on injecting contrast through the microcatheter. Fluoroscopic guided fallopian tube recanalisation (FTR) was performed in 21 cases. RESULTS: The procedure was successful with recanalisation of fallopian tubes in 15 cases. Pregnancy was seen in 3 cases (14.2%). Primary infertility was 71.4% and secondary infertility 28.6%. The mean time of the procedure was 21 minutes with a minimum of 10 minutes and maximum of 40 minutes. The fluoroscopy time was between 4 minutes to 20 minutes with a mean of 11 minutes. The patients who conceived had an average age of 28.2 years. CONCLUSION: The modified technique is simpler to perform with low cost, less trauma and procedure time with good results. This study highlights the need of using modified technique for ease of the procedure and reducing fluoroscopy time. PMID- 27407765 TI - A Laboratory Investigation into Oviposition Responses of Aedes aegypti to Some Common Household Substances and Water from Conspecific Larvae. AB - BACKGROUND: The surveillance of Dengue vector - Aedes aegypti, is routinely done by using ovitraps (a dark container filled with water and a wooden paddle/towel cloth provided as a oviposition substrate), which indicates the extent of Aedes activity in an area. METHOD: The study evaluated the oviposition responses of laboratory bred gravid Aedes aegypti to commonly available household substances by use of ovitrap method. RESULTS: Oviposition avoidance or deterrence was exhibited by gravid Aedes to ovitraps baited with salt, fenugreek, vinegar, lime juice, hibiscus leaves, radish and curry leaves, whereas positive oviposition response was noticed to waters from conspecific (of the same species) larvae and cumin seeds baited ovitraps. CONCLUSION: The study findings may be utilized by researchers for further chemical analysis of the active ingredients of the substances found promising with a view to explore the possibility of their use by community and individuals for Aedes surveillance and control. PMID- 27407766 TI - The Curse of HIV: How Well Prepared is our Paramedical Force? AB - BACKGROUND: HIV patient-care is determined by the knowledge and attitudes of the health care workers (HCWs) towards the disease and towards HIV-positive individuals. With increasing incidence of HIV, a need was felt to assess the preparedness of the health care providers in the Armed Forces. METHODS: A population based, cross-sectional, questionnaire based analytical study was undertaken among para medical workers in the setting of a medical college and tertiary care service hospital to assess the knowledge and attitudes of HCWs towards HIV. RESULTS: The study indicated that contrary to the expectations and general belief, important knowledge gaps regarding modes of transmission, clinical course, diagnosis and management of HIV infection still exist among the paramedical workers of the Armed Forces. CONCLUSIONS: The present study has highlighted the urgent need to review the training curriculum of our paramedical workers at all levels and undertake intensive on the job training. The study recommends that medical officers should take full responsibility for imparting correct knowledge and ensuring correct attitude among the paramedical workers. PMID- 27407767 TI - Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces. AB - BACKGROUND: HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV - DNA by Real time - PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals. METHODS: Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector. RESULTS: Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy. CONCLUSION: HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time - PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future. PMID- 27407768 TI - Etiology and Management of Zygomaticomaxillary Complex Fractures in the Armed Forces. AB - BACKGROUND: The nature of duties in the Armed Forces predisposes its personnel to various kinds of injuries. The rise in violence coupled with an exponential increase in motorized population has contributed towards maxillofacial injuries. The aim of this study was to determine the incidence, cause and pattern of various injuries resulting in fracture of the zygomaticomaxillary complex in Armed Forces personnel and their families. METHODS: A study was conducted between January 2001 - December 2002 in maxillofacial surgical wing of an Army Dental Centre with specific regard to age, sex, location and etiology of zygomaticomaxillary complex fracture. Out of 201 maxillofacial injuries received, 87 individuals were treated for zygomaticomaxillary fractures. Majority of the individuals were in their third decade of life and road traffic accident was the leading cause of the fractures. RESULTS: Uneventful recovery was there in 81 individuals (93.10%). Six patients (6.89%) had post operative complications in the form of enophthalmos, hypophthalmos, paraesthesia, diplopia and facial asymmetry. These complications were subsequently treated successfully as a secondary procedure for all the patients. CONCLUSION: Facial bones, especially of the middle third of the face, are composed of a network of fragile bones which give way in case of force to a lesser extent than other parts of the body. It is imperative to educate people regarding the importance of restraints and use of protective headgears/use of seat belts while travelling in motorized transport. PMID- 27407769 TI - Hepatitis C Virus Infection in Haemodialysis Patients: "Wolf in Sheep's Clothing". AB - BACKGROUND: 170 million people are infected with the Hepatitis C virus (HCV) around the world. Approximately 50%-70% patients infected with HCV develop chronic liver disease. Haemodialysis patients constitute an especially important group with high HCV prevalence. Outbreaks of HCV infection in dialysis units have been documented. Detection of anti-HCV antibodies is a convenient and conventional mode of documentation. However, in this group, it has it's own caveats. METHODS: 48 patients who had undergone or were on haemodialysis (HD) and had undergone a minimum of 15 dialysis sittings were studied. HCV infection was documented both by anti-HCV antibody detection and HCV RNA testing. A comparative evaluation of results by both tests was done. RESULTS: Out of a total of 48 patients, HCV RNA was detected in 38 (79.16%) and anti-HCV antibodies in 13(27.07%). Out of 48 patients 10(20.83%) were negative for both parameters. 22.91% (11/48) of patients were positive for both HCV RNA and anti-HCV antibody. 56.25% (27/48) were HCV RNA positive but anti-HCV antibodies were not detectable in their sera. 2 patients (04.16%) had a positive anti-HCV antibody status despite HCV RNA being negative. In 20.83% (10/48) both parameters were undetectable. CONCLUSION: Chronic liver disease (CLD), particularly due to HCV infection, is a major complication amongst haemodialysis (HD) patients. Without reliable assays for antigenemia and the inability of antibody tests to define viremia in all cases, the detection of viral nucleic acid is necessary for diagnosis of active HCV infection. PMID- 27407770 TI - Study of Drug Resistant Pulmonary Tuberculosis. AB - BACKGROUND: Drug resistance has emerged as a major problem in management of pulmonary tuberculosis (PT) with increase in its incidence. METHODS: Sixty patients who presented to a tertiary referral chest centre with drug resistant PT were included in the study out of 835 clinically diagnosed cases of PT treated between January 2000 and May 2002. They were studied to see the incidence, pattern of drug resistance and response to treatment. RESULTS: 7.2% of the clinically diagnosed cases of PT had drug resistance and 14.8% of the 403 strains of mycobacterium tuberculosis (MTB) tested were resistant to one or more antitubercular drugs (ATD). 40 cases (66.7%) had initial resistance and acquired resistance was seen in 20(33.3%) out of the 60 cases of drug resistant PT. Single drug resistance was observed in 21 cases (35%), two drug resistance in 19 (31.7%) and 20(33.3%) cases showed resistance to three or more drugs. Individual drug resistance breakup was: INH(H) - 36(8.9%), Rifampicin (R)-38(9.4%), Ethambutol (E) - 14(3.5%), Streptomycin (S) - 34(8.4%), Pyrazinamide (Z) - 2(0.5%), Ciprofloxacin (C) - 2(0.5%), Ethionamide (N) - 2(0.5%), Cycloserine - 1(0.3%) and Kanamycin - 1(0.3%). 98.3% showed sputum conversion after starting reserve drugs. Average period of sputum conversion was 10 weeks. 3.3% were HIV positive. CONCLUSION: Incidence of drug resistance was not as high as reported by some other workers and majority of the cases showed satisfactory outcome. PMID- 27407772 TI - Management of Soft Tissue Defects of the Ankle and Foot. AB - BACKGROUND: Treatment of soft tissue defect of ankle and foot has always been a challenging problem. METHODS: Thirty patients with soft tissue defects of the ankle and foot who underwent various reconstructive procedures in two tertiary care teaching hospitals were studied. RESULTS: Most of the defects (33%) were located in and around the ankle. Trauma was the major cause (56.6%). Defects were reconstructed with a variety of local, regional, distant and microvascular free flaps. Distally based superficial sural artery flap was used in majority of the cases (40%). Free tissue transfer using radial artery forearm flap was done in three (10%) complex wounds where other flaps were not found to be suitable. Superficial soft tissue defects on the dorsum of foot were resurfaced with split thickness skin grafts in 3 (10%) cases. Out of 27 flaps used, 26 survived completely. One inferiorly based fasciocutaneous flap developed partial necrosis. There was graft loss in one patient which required regrafting with the stored autograft. CONCLUSION: Distally based superficial sural artery flap remains the choice for reconstruction of soft tissue defects of ankle and foot because of its reliable blood supply and easy elevation. PMID- 27407771 TI - Ultrasonography in Patients with Suspected Acute Appendicitis. AB - BACKGROUND: To evaluate the usefulness and limitations of graded compression ultrasonography in the diagnosis of clinically equivocal cases of suspected acute appendicitis at the setting of mid zonal military hospital of India. METHODS: A prospective study, graded compression ultrasonography with self localization was carried out with 3.5 MHz convex, 5 MHz convex and 7.5 MHz linear transducers (Wipro GE) in 69 clinically equivocal suspected cases of acute appendicitis. With maximal compression the anteroposterior diameter of appendix was measured from outer to outer wall. The main criterion for diagnosing appendicitis was demonstration of a non compressible appendix with anteroposterior dimension of 7mm or more. RESULT: Sonologically 36 (52%) cases were diagnosed as appendicitis. Anteroposterior outer diameter of inflamed appendices ranged from 7mm to 21mm (mean 10.5mm). 30 (83%) of 36 patients could accurately self localize the point of maximum tenderness. There were 01 false positive and 04 false negative cases. Sensitivity and specificity were 89.7% and 96.6% respectively. Positive and negative predictive values were 97.2% and 87.8% respectively. Alternative diagnoses were offered in 33 (47.8%) cases. Amongst these 33 cases, 14(42.4%) had abdominal pain of unknown origin. Gynaecologic, urologic and gastrointestinal aetiologies were established in 10(30.3%), 07(21.2%) and 02(6%) cases respectively. CONCLUSION: Graded compression ultrasonography superadded with self localization is an accurate means of diagnosing/excluding appendicitis in clinically equivocal cases of acute appendicitis and it is of great value in establishing alternative diagnoses. PMID- 27407773 TI - Clinical Autopsy vs Medicolegal Autopsy. AB - Post mortem examination of a dead body is carried out to gain insight into the disease process as well as for forensic application of medical knowledge. Although different specialists viz; pathologists and forensic medicine experts, carry out autopsy for these two purposes, on many occasions there may be overlap of these two fields of medicine. A comparative analysis of both these categories of autopsies, namely clinical autopsy and medico legal autopsy, is done in this article with the intention of equipping the specialists in these two fields of medicine with knowledge about the other. PMID- 27407774 TI - Amendments to Indian Drugs and Cosmetics Act and Rules Pertaining to Blood Banks in Armed Forces. PMID- 27407775 TI - Genomic Diversity of Human Immunodeficiency Viruses. AB - BACKGROUND: Globally circulating strains of human immunodeficiency virus type one (HIV-1) exhibit an extraordinary degree of genetic diversity. Sequences derived from HIV-1 strains have historically been classified on the basis of their phylogenetic relationships. The viruses have been classified into groups, subtypes or clades and circulating recombinant forms (CRFs). Groups were originally named M for main, O for outlier and N for Non-M-Non-O. The identification of subtypes and CRFs provides a means of tracking the dissemination of the pandemic. METHODS: Various methods to study the molecular epidemiology of HIV-1 are virus isolation, cloning, DNA sequencing, restricted fragment length polymorphism of the molecularly cloned and amplified genome (PCR RFLP), RNase mismatch cleavage analyses of RNA, RNA heteroduplexes derived from culture amplified virus, primer mismatch sensitive PCR to identify specific mutations, single strand conformational polymorphism (SSCP) to localize mutations arising over short regions of env gene, denaturing gradient gel electrophoresis and serological assays based on V3 peptide. Except for PCR-RFLP and denaturing gradient gel electrophoresis, these techniques do not easily allow simultaneous analyses of multiple sequence variants and include the laborious and selective process of virus co-cultivation or molecular cloning prior to analyses. The extensive DNA sequence analyses remain the gold standard for epidemiological investigations. CONCLUSIONS: Both HIV-1 and HIV-2 are present in India. The Indian strains of HIV1 also show diverse subtypes with HIV1 subtype C predominance. Tracking the genetic diversity has implications towards understanding the evolution of the epidemic, immunopathogenesis, natural course of infection, response to therapy and most importantly vaccine design. PMID- 27407776 TI - Modified Technique of LSCS: The Misgav Ladach Method. PMID- 27407777 TI - An Unusual Case of Incisional Hernia. PMID- 27407778 TI - Congenital Muscular Torticollis. PMID- 27407779 TI - Post-traumatic Pseudocyst of the Spleen. PMID- 27407780 TI - Subdural Empyema: A Rare Complication of Chronic Otitis Media. PMID- 27407781 TI - Adult Bochdalek Hernia. PMID- 27407782 TI - Anaesthetic Management of a Case of Early Pregnancy with Systemic Sclerosis. PMID- 27407783 TI - Ego Strengthening and Eye Movement Desensitization Reprocessing in Post Traumatic Stress Disorder. PMID- 27407784 TI - Congenital Bronchoesophageal Fistula in an Adult. PMID- 27407785 TI - Giant Occipital Encephalocele. PMID- 27407786 TI - Arteriovenous Malformation in Mandible. PMID- 27407787 TI - Non-Syndromal Facial Asymmetry. PMID- 27407788 TI - Collateral Benefit of Deltamethrin Impregnated Mosquito Nets. PMID- 27407789 TI - Pulmonary Oedema in a Survivor of Suicidal Hanging: Reply. PMID- 27407790 TI - Pulmonary Oedema in a Survivor of Suicidal Hanging. PMID- 27407791 TI - High Altitude and its Illness: Reply. PMID- 27407792 TI - High Altitude and its Illness. PMID- 27407793 TI - Quinolones Losing Favour in Enteric Fever. PMID- 27407794 TI - Evolution in Fracture Management. PMID- 27407795 TI - Tamoxifen Therapy for Breast Cancer and Endometrial Pathology. AB - BACKGROUND: Tamoxifen, used as adjuvant therapy for carcinoma breast in postmenopausal women to prevent relapse has estrogenic effect on the endometrium. METHODS: 104 patients on tamoxifen for more than six months were subjected to a clinical examination and transvaginal sonography. Patients with endometrial thickness > 8 mm were further evaluated by hysteroscopy and endometrial biopsy. RESULTS: 35(34%) patients were symptomatic. The average endometrial thickness was 11.2 mm which correlated with duration of tamoxifen use. 27(48%) patients had abnormal hysteroscopic findings. 35 (63%) of endometrial biopsies revealed abnormal endometrium. One case of endometrial carcinoma was diagnosed. The results were statistically analysed. There is a significant association between symptomatic status and endometrial thickness and duration of tamoxifen use. CONCLUSION: All patients on long term tamoxifen should be annually screened for endometrial pathology. PMID- 27407796 TI - Platelet Functions in Cardiopulmonary Bypass Surgery. AB - BACKGROUND: Haemorrhage after Cardio Pulmonary Bypass (CPB) Surgery is a well recognised complication that leads to significant morbidity and mortality. The incidence varies between 5-25% depending upon the clinical situation. Several factors are implicated as causative but none have been precisely proved. METHODS: Our study was an attempt to evaluate the haemostatic defect with particular reference to platelet function abnormalities during cardio pulmonary bypass surgery, in order to reduce the morbidity and mortality associated with post CPB haemorrhage. Flow cytometric evaluation of different platelet glycoproteins like GPIb/IX, GPIIb/IIIa and GMP-140 was done. RESULTS: The marker expression showed deregulation during surgery which returned to base after bypass was terminated. In contrast, the cases with bleeding showed significant variation. P-Selectin (GMP 140) expression decreased progressively till 3(rd) post-operative day showing lack of activation of platelets in cases of severe bleeding. CONCLUSION: Longer duration of CPB initiates plasmin generation through heparin, which raises the PAI-1-tPA complex and thereby down regulating the functions of platelets. This suggests a link between duration of CPB, bleeding, platelet dysfunction and fibrinolysis. Hence serial estimations of the levels of GMP-140 and tPA can predict severe bleeding. PMID- 27407797 TI - Correction of Lower Limb Deformities Using Ilizarov's Technique. AB - BACKGROUND: India accounts for approximately 10 million orthopaedically handicapped children and adults with limb deformity. Ilizarov ring fixator could treat most of these deformities. METHODS: Twenty cases of deformities of lower limb managed with Ilizarov technique during period between March 2001 and February 2003 were studied. RESULTS: 55% were in the age group of 11-30 years. Out of the 20 cases studied, 6 were congenital talipes equino varus, 8 were fixed flexion deformity of knee, 4 were equines deformity of the ankle and 2 were malunited fracture shaft of tibia.4 patients who had recurrence were operated for fixed flexion deformity of the knee. The main complication encountered was pin tract infection, which was seen in 15(75%) cases. In 16(80%) cases, the results were excellent with no recurrence of deformity and patients were able to walk independently. In 4 (20%) cases, recurrence was mild to moderate (10 to 20) but all of them were able to ambulate idependently and carry out their routine activities. CONCLUSION: Ilizarov ring fixator is a superior compared to conventional methods for correction of deformities of lower limb. PMID- 27407798 TI - Outbreak of Viral Hepatitis E in a Regimental Training Centre. AB - BACKGROUND: An outbreak of viral hepatitis occurred in a regimental centre with 265 cases occurring during a 3 months period. METHODS: 190 serum samples were tested for IgM antibodies against viral hepatitis E by Enzyme Immuno Assay (EIA) and for antibodies against Hepatitis A and Hepatitis B viruses. Epidemiological investigation comprised review of surveillance data, filling up epidemiological case sheet, sanitary survey, inspection of water supplies and bacteriological examination of water for coliforms. RESULT: 97.4% of the serum samples were positive for IgM antibodies against Hepatitis E virus. Two leaks were detected in water pipelines, which were passing through contaminated areas around improperly functioning septic tanks and soak pits. The attack rate among recruits being supplied water through leaking pipelines was 11.1% whereas it was 2.89% in those not directly exposed. This difference was statistically significant (p<0.001). Bacteriological examination of water showed a high coliform count. CONCLUSION: The outbreak of viral hepatitis E occurred due to sewage contamination of water pipelines. PMID- 27407799 TI - Terrorism, Trauma and Children. AB - BACKGROUND: Terrorist attacks, armed conflict and all forms of catastrophe, tax our ability to cope, understand and respond to the situation. Children are more vulnerable. MATERIAL & METHOD: 16 children, victims of a terrorist attack in an army residential camp were managed for their physical injuries and evaluated for psychological trauma. RESULTS: All patients recovered from physical injuries, except one baby of two months, who died due to severe chest trauma. 5 children presented with Acute Stress Reaction. 3 recovered well and two, showed persistent poor scholastic performance even after one year. CONCLUSION: A terrorist attack, not only results in physiscal scars but also causes psychological trauma, which requires emotional support and needs to be followed up on a long term basis. PMID- 27407800 TI - Hepatitis G Virus: Prevalence in Blood Donors in Armed Forces. AB - BACKGROUND: A new RNA virus designated hepatitis G virus (HGV) was recently identified. Because HGV has less than 25% sequence or amino acid homology with hepatitis C virus (HCV) and other established Flaviviridae, it is considered to be a new genus in this growing family of hapatotropic viruses. Hepatitis G virus has been associated with hepatitis and is transmitted through parenteral and sexual route. MATERIAL AND METHODS: A study comprising 500 healthy voluntary blood donors (service personnel) was under taken to find out prevalence of HGV. HGV RNA was detected by reverse transcriptase - polymerase chain reaction (RT PCR). Hepatitis B surface antigen (HbsAg) and antibody to HCV were detected by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: Thirteen donors (2.6%) were positive for HGV RNA. 17 donors (3.4%) were positive for antibody to hepatitis C virus (HCV) by ELISA. Co-infection of HGV with hepatitis B virus (HBV) was seen in 5 donors and with HCV infection in 2 donors. Co-infection of HGV, HBV and HCV was not seen in any donor. CONCLUSION: So far there is no conclusive evidence that HGV produces hepatitis. But presence of HGV in hepatitis cases casts a doubt on this finding. Prevalence rate in blood donors may be helpful in future studies when the exact role of HGV is known. PMID- 27407801 TI - Diagnosis of Malaria Infection Using Non Radioactive Malaria Diagnostic System (NOMADS). AB - BACKGROUND: Malaria remains one of the leading causes of morbidity and mortality. A definitive and early diagnosis remains the biggest challenge world-wide. Light microscopy of blood smears has been the gold standard in diagnosis of malaria for decades. This routine microscopic diagnosis is often unreliable and may not be available at many peripheral health centers. Hence newer diagnostic techniques have been developed based on antigen detection. METHOD: Microscopy and Non radioactive Malaria Detection System (NOMADS) to diagnose falciparum malaria were compared. Specificity and sensitivity of this technique and applicability of the kit for rapid and reliable malaria diagnosis were evaluated. 2579 samples of blood were processed. Both thick and thin blood smear examination and NOMADS was carried out on each of them. All smear positive samples and highly suspicious clinical cases were also subjected to detection of HRP-2 antigen by ICT Malaria Pf test. RESULTS: The detection rate for malaria on smear examination (both vivax and falciparum) was highest at Dimapur (7.41%), followed by Tezpur (7.13%), Kolkata (7%), Guwahati (6%) and Changsari (3.6%). All centers had greater incidence of falciparum compared to vivax except Kolkata where only vivax was detected. The sensitivity of NOMADS was 0%, 4.8%, 13.5%, 42.9% and 52.8% at Kolkata, Tezpur, Guwahati, Changsari and Dimapur respectively. The specificity of the test ranged between 91.8% at Changsari to 95.9% at Dimapur. The specificity at Tezpur, Kolkata and Guwahati was 92.3%, 94% and 95.3% respectively. CONCLUSION: The study revealed that the test kit developed needs to be standardised as regards calculation of cut off values for each of the test runs and reproductibility of optical density readings. Immuno-Chromatography Test (ICT) is helpful in early diagnosis, management and follow-up of cases of malignant malaria. PMID- 27407802 TI - Extrapulmonary Tuberculosis in Human Immunodificiency Virus Infection. AB - BACKGROUND: In view of increase in incidence of exptrapulmonary tuberculosis after the epidemic of human immunodeficiency virus infection, the clinical profile of extrapulmonary tuberculosis in patients with HIV infection was studied. METHOD: The study population comprised patients of HIV infection with extrapulmonary tuberculosis. Work up included history, clinical examination, sputum for acid fast bacilli, chext X-ray, ultrasonography (USG) abdomen, fine needle aspiration cytology(FNAC), transbronchial needle aspiration (TBNA) and computed tomography of chest. RESULTS: There were 50 cases, all males with mean age of 35 years. 24(48%) were without pulmonary tuberculosis and 26(52%) had pulmonary tuberculosis. 41(82%) had disseminated disease and 9(18%) involve one site. Fever and weight loss were the most frequent symptoms (79% and 58% respectively) in cases without pulmonary tuberculosis. The most frequent extrapulmonary site was lymph node in 46(92%), followed by spleen in 13(26%), pleura 9(18%), miliary 7(14%) and hepatic 1(2%). The diagnosis was confirmed by invasive methods in 30 out of 50(60%) cases [FNAC in 23(88%), TBNA in 2(25%) and pleural biopsy in 5(55%)]. CONCLUSION: In HIV infected patients, the most common extrapulmonary site is lymph mode followed by spleen. PMID- 27407803 TI - Antibiotic Use in Neonates of Birth-weight < 2000 G Surviving to Discharge. AB - BACKGROUND: Symptoms and signs of infection are non-specific in neonates. Hence, neonates, especially low birth-weight and premature ones, often receive empirical antibiotics. This study was conducted to assess the use of antibiotics in newborns with a birth-weight of < 2000 g at a tertiary care service hospital. METHODS: All infants < 2000 g at birth admitted to NICU were include Data on symptoms, investigations for infection and use of antibiotics were collected in addition to baseline data. The data of those surviving to discharge was analyzed. RESULTS: Out of 52 eligible infants, 3 died; thus data from 49 neonates was analyzed. Preterm infants formed 89.8% of this group while 36.73% were Small for Gestational Age (SGA). Symptoms were present in 22 (44.9%) of whom 13(59.1%) received antibiotics. Lower birth weight, lower gestational age and male sex predisposed to increased antibiotic use. A total of 21 courses of antibiotics were administered which averaged to 1.6 course or 15 days of therapy per patient. The most common combination used was cefotaxime-amikacin in 42.9% followed by ampicillin-gentamicin in 33.3%. The overall mortality for this group was 5.8% while mortality due to infection was 1.9%. CONCLUSION: Attention to asepsis in the NICU, close monitoring and judicious use of antibiotics only when indicated can result in decreased empirical use of antibiotics and better outcome. Low birth-weight, prematurity and male sex are significantly associated with antibiotic use in this study. PMID- 27407804 TI - Distraction Osteogenesis in Management of Mandibular Deformities. AB - BACKGROUND: The concept of Distraction Osteogenesis is applied in Maxillofacial surgery extensively in the recent past, revolutionizing the concept of management of facial deformities specially the mandible. METHODS: This article describes intra oral mandibular distractors in managing mandibular deformities in 9 cases. CONCLUSION: Surgical intervention is possible in very young patients. Distraction Osteogenosis does not reduce the need for orthodontic intervention. A multifarious approach to the problem, should form the basis of treatment of mandibular deformities. PMID- 27407805 TI - Difficulties in Immunohaematology : The Weak D Antigen. AB - BACKGROUND: The Rh blood system is one of the most polymorphic and immunogenic systems known to humans. The expression of Rh blood group antigen is complex. The Rh D antigen is the most important of the antigens that constitute the Rh antigen system. In most cases, D antigen can easily be detected. However, due to variability of expression, weak forms antigen are encountered. The reactivity of weak D with antisera is variable and presents as a problem in blood banking. METHODS: A retrospective analysis for a five-year period was done. Blood samples that were negative for Rh D by immediate spin tube method were tested for weak D antigen by additional lab tests. RESULT: Of 34932 serial Rh grouping tests done in our Blood Bank, the incidence of weak D Rh antigen was 0.189%. All these were confirmed by the antiglobulin test. CONCLUSION: These patients present as a problem for the blood banker and a curiosity to the clinician. Although uncommon, all health care workers should be aware of this entity to avoid anti D alloimmunisation. PMID- 27407806 TI - IgM Chlamydia Trachomatis Antibodies in Cases of Melasma. AB - BACKGROUND: Melasma is an acquired photosensitive hypermelanosis in sun-exposed areas, especially seen in females. The exact cause of this disorder is not known. Association of melasma with chronic pelvic inflammatory disease (PID) has been described earlier. Chlamydia trachomatis is an important etilogical agent in acute and chronic PID and photosensitivity has been described in almost 50% cases of chronic lymphogranuloma venereum caused by 1.1, 1.2 and 13 serovars of C. trachomatis. METHOD: Blood of 38 cases of melasma in women and 31 healthy females was tested for the presence of C. trachomatis IgM antibodies by ELISA. RESULTS: The average age of the patients was 35.6(range 19-51) years and that of controls was 38(range 24-55). 7(18.42%) and 5 (13.16%) of the patients of melasma were positive and borderline positive for IgM antibodies respectively. None of the healthy controls were positive. The difference was statistically significant. CONCLUSION: Melasma in women is most likely due to photosensitivity to C.trachomatis in cases of chronic pelvic inflammatory disease. PMID- 27407807 TI - ENT Disabilities in Candidates for Recruitment. AB - BACKGROUND: Recruitment in the Army is subject to medical fitness as per laid down standards. A study of the frequency of referral and rejection gives us an understanding as to where to lay stress in the Ear Nose Throat Examination during recruitment medical. METHOD: A three year analysis of candidates reporting for review of ENT disabilities was carried out from January 1999 to December 2001. RESULTS: Of the 1156 candidates, 888(76.8%) were found to be fit. The commonest cause for rejection was Wax in ears in 496 cases (43%). 428(86.3%) were found to be fit on review. Chronic suppurative otitis media (21.9%) and tympanosclerosis (21.3%) were the other causes for rejection. CONCLUSION: The desirable situation is wherein the evaluation by the specialist is in minimal variation with that of the initial recruitment medical examination. Awareness to have ears cleaned for wax before appearing for the examination, provision of better examination ambiance and equipment and a short training capsule will be beneficial to reduce the number of review cases to referral hospitals. PMID- 27407808 TI - Japanese Encephalitis : Is Routine Immunization Required? AB - Japanese encephalitis is the leading cause of viral encephalitis in Asia. In endemic areas annual incidence ranges from 10-100 per 100000 population. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropshychiatric sequelae. There is no effective drug treatment for this disease. In recent decades, Japanese encephalitis virus has caused epidemics in previously unaffected countries like India, Myanmar, Nepal, Sri Lanka, Thailand and Viet Nam. No effective environmental control is known. Although socioeconomic improvement and changes in agricultural practices are likely to reduce viral transmission, large-scale vaccination of affected populations with an effective and affordable vaccine appears logical at least in the short term. The impact of large-scale Japanese Encephalitis vaccination is documented in some regions of China and systematic vaccination has contributed to significant decline in incidence in Japan, Republic of Korea and Thailand. PMID- 27407809 TI - Impact of Multidetector CT on 3D CT Angiography. AB - 3D Computed Tomographic Angiography (CTA) is a noninvasive volumetric imaging technique increasingly used for evaluation of vascular system. The introduction of Multidetector CT (MDCT) has increased scanning speed, allowing shorter acquisition time, greater volume coverage and decreased contrast requirement while diminishing respiratory motion artifacts. Thin-slice collimation protocols are routinely used which generate isotropic 3D voxels that improve image quality. The ideal CTA study requires scanning at peak vascular enhancement for optimal opacification of arteries with separation of arteries and veins. MDCT has enabled complete lower extremity inflow and runoff studies with a single injection, as well as thin-section CTA covering the entirety of the Carotid arteries and Circle of Willis. Sixteen row MDCT has increased scanning speed further facilitating the development of novel applications such as coronary CTA. CTA when perfomed with MDCT offers a "one scan - many views" option useful in imaging vascular diseases. CTA has important advantages over conventional angiography, such as reduced risk, diminished time and better patient acceptance. With MDCT, 3D CTA is crossing vessel tortuosity and evaluation of vessel fragility. PMID- 27407810 TI - Polio Eradication in India: Myth or Reality. AB - BACKGROUND: Poliomyelitis has been eradicated from large parts of the world. In South East Asian Region, India and Pakistan remain the only countries where active transmission of the disease persists. A decade-long initiative to eradicate the disease is in progress in India. Initial results were encouraging, with the number of fresh polio decreasing till 2001. The year 2002, however, witnessed a setback, with significant rise in cases of poliomyelitis. METHODS AND RESULTS: The eradication measures have been reviewed. The corrective measures appear to be succeeding. Various facets of eradication and their impact are evaluated. CONCLUSION: Poliomyelitis is controlled but the ultimate target of eradication may still be elusive, keeping in mind operational lacunae and vaccine virus characteristics. PMID- 27407811 TI - Radiosynoviorthesis in the Treatment of Disabling Arthritis. PMID- 27407812 TI - Meningococcal Meningitis. PMID- 27407813 TI - Nesiritide - A New Agent For Acute Decompensated Heart Failure. PMID- 27407814 TI - Rudimentary Horn Pregnancy. PMID- 27407815 TI - Sarcoidosis following Chemotherapy of Essential Thrombocythemia with Hydroxyurea. PMID- 27407816 TI - Gastrointestinal Stromal Tumour (GIST) From an Imaging Perspective. PMID- 27407817 TI - Uterine Lipoma - A Rare Entity. PMID- 27407818 TI - Hydramnios Associated with Foetal Duodenal Atresia. PMID- 27407819 TI - Kluver - Bucy Syndrome Following Herpes Simplex Encephalitis. PMID- 27407820 TI - Case of Objective Tinnitus. PMID- 27407821 TI - Bilateral Emphysematous Pyelonephritis. PMID- 27407822 TI - Exertional Rhabdomyolysis Causing Acute Renal Failure. PMID- 27407823 TI - Laparoscopy: How good could it get!: REPLY. PMID- 27407824 TI - Laparoscopy: How good could it get! PMID- 27407825 TI - Congenital Lobar Emphysema: Diagnosis and Management: REPLY. PMID- 27407826 TI - Congenital Lobar Emphysema: Diagnosis and Management. PMID- 27407827 TI - Prehypertension: A necessity !!! PMID- 27407828 TI - Prehypertension: A necessity !!!: REPLY. PMID- 27407829 TI - Introduction of Modern Stretchers in the Armed Forces. PMID- 27407830 TI - Introduction of Modern Stretchers in the Armed Forces: Reply. PMID- 27407831 TI - Unstable or High Risk Plaque: How Do We Approach It? PMID- 27407832 TI - Newer Frontiers in Hearing Rehabilitation. PMID- 27407833 TI - AC/PC Intraocular Lens Exchange with Penetrating Keratoplasty in Pseudophakic Bullous Keratopathy. AB - BACKGROUND: Evaluation of penetrating keratoplasty in cases of pseudophakic bullous keratopathy with AC/PC IOL exchange. METHODS: This retrospective study included 120 cases of pseudophakic bullous keratopathy managed over 9 years at three tertiary care eye centres followed up for 4 years. Cases were taken up for penetrating keratoplasty along within adjuvant procedures like IOL explantation and Secondary Posterior Chamber IOL implantation over the frill of posterior capsule. RESULTS: Lens exchange with Penetrating Keratoplasty (PK) was done in 93 and PK without lens exchange in 27 cases. 25% required systemic steroids for 2-3 weeks. Re-grafting was performed in 5% and 85% attained moderate visual acuity. CONCLUSION: Intra ocular lens exchange and Posterior chamber IOL are suitable for penetrating keratoplasty in terms of optical clarity, graft survival and visual outcome. PMID- 27407834 TI - Misoprostol as aid in First Trimester MTP. AB - BACKGROUND: Medical Termination of Pregnancy (MTP) is a commonly performed during the first trimester. Dilatation and Evacuation (D & E) mandates rapid dilatation of cervix with metal dilators, which requires anaesthesia and may be associated with trauma to the uterus, cervix and later cervical incompetence. The problem of rapid cervical dilatation is obviated with intravaginal misoprostol. METHODS: Intravaginal misoprostol tablet 200 microgram was inserted, a night prior to MTP to ripen the cervix. Cervix was dilated with metal dilators only in cases where cervix did not loosen up sufficiently. Products of conception were removed by suction. RESULTS: Out of 108 cases cervical dilatation was not required in 96 cases (88.9%). CONCLUSION: Intravaginal misoprostol 200 microgram proved effective as a priming agent prior to MTP in the first trimester. PMID- 27407835 TI - Spiral CT Angiography: Applications in Neurovascular Imaging. AB - BACKGROUND: The advent of Spiral Computed Tomographic (CT) angiography has provided the patients a non-invasive, accurate and fast modality of imaging the vasculature. METHODS: Spiral CT angiography was performed in 30 patients to evaluate intracranial circulation using standard protocols of data acquisition. The images were processed and reconstructed in 3-dimension to delineate anatomy and pathology accurately. RESULTS: The study established that CT angiography is an accurate modality for evaluating the intracranial circulation in a variety of abnormalities. It is safe both in terms of being non-invasive and exposure to radiation. It has a distinct advantage over other non-invasive modalities of imaging like MRI in the evaluation of patients with metallic stents and clips. CONCLUSION: CT angiography has tremendous potential in imaging the intracranial vasculature. It is unquestionably safer than catheter angiography as it avoids arterial puncture and intra-arterial catheter manipulation. It is fast and capable of producing excellent 3-dimensional images of the intracranial vasculature. PMID- 27407836 TI - Hepato-biliary Scintigraphy in diagnosis of Biliary Atresia. AB - BACKGROUND: Biliary Atresia and Neonatal Hepatitis are the two major causes of Persistent Neonatal Jaundice. Differentiation is done by biochemical and radiological tests. Radiological investigations use intra-or extra-hepatic biliary dilation for diagnosing biliary atresia but this is not always reliable. METHODS: 14 neonates with persistent conjugated hyperbilirubinemia who had undergone hepato-biliary scintigraphy were retrospectively evaluated and those having Extrahepatic Biliary Atresia were analyzed with reference to operative findings. RESULTS: 11 out of 14 had Extrahepatic Biliary Atresia during operation whereas 3 proved to be false positive. CONCLUSION: Mebrofenin hepato - biliary scintigraphy is a simple, safe, accurate and cost effective investigation for diagnosis of biliary atresia. PMID- 27407837 TI - Helicobacter pylori in Dyspepsia - Antibiotic Sensitivity and Virulence Patterns. AB - BACKGROUND: Helicobacter pylori is implicated in acute superficial gastritis, chronic atrophic gastritis, gastric carcinoma and MALT associated lymphoma. Though colonization can occur in normal individuals, treatment is given if the organism is associated with virulence factors like vacuolating toxin and cytopathic toxin as coded by vacA and cagA genes respectively. No causal relationship between non-ulcer dyspepsia (NUD) and H pylori has been established. This study was carried out to delineate colonizers from pathogens so that appropriate treatment can be planned. METHOD: 100 patients were recruited, 62 with NUD and 38 age and sex matched controls. 4 gastric biopsies and a serum samples were taken from each patient. The biopsies were examined for H pylori by culture, histopathology, rapid urease test, PCR and serum for IgG, IgM and IgA. RESULTS: Culture showed 22.6% positivity and urease 19% among the test group. Histopathology showed 53.2% superficial gastritis and 30.6% chronic gastritis among the test group (P<0.001), PCR for H pylori was positive in 48.3% and vacA and cagA were 29% and 22.6% respectively (P=0.001) among the tests. IgG, IgM and IgA were 41.9%, 46.8% and 43.5% respectively. CONCLUSION: The culture and rapid urease tests were highly specific with high positive predictive value but if negative, infection cannot be ruled out. Similarly IgA and IgM positivity has high positive predictive value for on-going infection where as IgG may be positive in old healed infections also. PCR assay in biopsy specimens is a valuable technique for detection of H pylori with high specificity and sensitivity. The presence of vacA and cagA genes can differentiate innocuous bystanders and potentially invasive organisms. PMID- 27407838 TI - Low Level Laser Therapy in Treatment of Stress Fractures Tibia: A Prospective Randomized Trial. AB - BACKGROUND: Standard treatment of Stress fracture includes rest, compression, elevation and passive stretching. Low level laser therapy (LLLT) has been described in treatment of joint conditions, tendophaties, musculofascial pains and dermatological conditions. A prospective randomized control study was carried out to assess efficacy of LLLT in treatment of stress fractures in tibia. METHOD: 68 cases were enrolled. 34 each in control and test group. Control cases were treated with placebo and test group with laser-therapy. Complete resolution of pain and tenderness, and return to painless ambulation was taken as end point of therapy in both groups. RESULT: The test group showed earlier resolution of symptoms and painless ambulation with fewer recurrence. CONCLUSION: LLLT appears beneficial in treatment of stress fracture in this preliminary study. A larger multicentric study is indicated to prove the benefit conclusively. PMID- 27407839 TI - Epidemiological Investigation of Forest Malaria among GREF and Army Personnel. AB - BACKGROUND: General Reserve Engineering Forces (GREF) engaged in road construction and military personnel camping in forest areas are at high risk of contacting malaria. METHOD: All cases of malaria were confirmed by peripheral blood smear examination. Neighbouring civilian houses were visited, members interviewed and blood slides taken. Environmental survey included mosquito and larval collection. Epidemiological data on malaria in the state and the district was obtained from civil health authorities. RESULTS: During April-June 2001 there were 27 cases of malaria amongst GREF and army personnel out of 91 deployed giving an attack rate of 29.67%. The attack rate was significantly more in GREF personnel (45%) compared to army personnel (17.65%). All the cases were falciparum malaria. Out of 20 randomly collected blood slides from the civil laborers, 2 (10%) were positive for falciparum malaria. CONCLUSION: For small patrols operating in hyperendemic malarious areas strict personnel protective measures besides chemoprophylaxis needs to be implemented. PMID- 27407840 TI - Posterior Interosseous Artery Flap for Hand Defects. AB - BACKGROUND: Reconstruction of soft tissue defects in the hand need an early, single stage and well vascularised cover to achieve the best functional result. Usually a full thickness graft is required since vital structures like tendons, bones and joints are exposed and often there is need for secondary reconstruction. METHODS: We managed 12 cases of complex defects over the hand in the last 2 years with the posterior interosseous artery flap. RESULTS: In 5 cases the defect was due to blast injury and in 4 because of crush injury. Males predominated in the ratio of 5:1. The defect was most often in the 1(st) web space and the largest flap was 11*8 cm. In all but one case the donor site was covered by split skin graft, which settled well. 2 patients had superficial flap necrosis needing debridement and skin graft. CONCLUSION: Flap based on reverse flow in the posterior interosseous artery is a versatile and reliable source for full thickness cover of complex soft tissue defects in the hand. PMID- 27407841 TI - Amputation in Diabetic Patients. AB - BACKGROUND: Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. The present study examines the amputation risk criterion and the long term outcome in terms of amputations and mortality in patients with diabetic foot. METHODS: 27 patients with diabetic foot lesions were studied. There were 15 patients with early lesions and 10 with advanced lesions. 15 patients were managed conservatively including local amputations and 12 with lower extremity amputations. 80% patients were males in 45-59 years of age group and all patients had more than 6 years of poorly controlled diabetes. RESULTS: Precipitating factors included walking barefoot, history of minor trauma, infection, callosities or burns in 86% of patients. Major lower limb amputations were common in irregularly treated, poorly controlled diabetics due to infection in a limb devitalized by angiopathy and desensitised by neuropathy. CONCLUSION: Diabetic foot ulcers are associated with high morbidity and mortality. Mortality was higher in ischaemic ulcers than neuropathic ulcers. PMID- 27407842 TI - Study of Pigtail Catheters for Tube Thoracostomy. AB - BACKGROUND: To study the efficacy and complications of percutaneous small bore pigtail catheters for tube thoracostomy. METHODS: 50 cases of pleural effusion requiring drainage were enrolled in the study. Pigtail catheters of the size 9 to 12 F were used. RESULTS: The procedure was successful in 46/50 (92%) cases. Fibrinolytic therapy and pleurodesis was successful through these tubes. Complications included blockade in 4 (8%), small pneumothorax in 10 (20%) and chest pain at tube thoracostomy site requiring analgesics in 30 (60%). CONCLUSION: Small bore pigtail catheters are safe, comfortable, cost effective and have few complications especially in loculated pleural effusions. PMID- 27407843 TI - Blistering Beetle Dermatitis: An Outbreak. AB - BACKGROUND: Blister beetles, which are abundant in Madhya Pradesh and Punjab cause peculiar skin lesions. We came across large number of such cases. METHOD: This descriptive study comprised 46 cases of Blistering beetle dermatitis who presented to skin OPD, over a period of one month from 17 April to 15 May 2002. RESULT: All cases belonged to one company of soldiers deployed near an agricultural land. Of the total of 245, 46 personnel suffered from blistering beetle dermatitis with an incidence of 18.7%. A thorough epidemiological investigation was undertaken and beetles of Paederus Fucipes were found incriminating. Further spread was effectively controlled by timely spray of Baygon and Malathion over the infested land. CONCLUSION: In an outbreak of bizarre dermatitis, diagnosis of blistering beetle dermatitis should be kept in mind. Timely diagnosis, epidemiological investigation and insecticide spraying brings down the incidence of new cases. PMID- 27407844 TI - Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment. AB - BACKGROUND: Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment. METHODS: Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fisher's exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year. RESULTS: Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATT-induced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity. CONCLUSION: ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases. PMID- 27407845 TI - Intrapartum Electronic Foetal Monitoring : Does it Lead or Mislead? PMID- 27407846 TI - Emergencies in Dermatology : Acute Skin Failure. AB - Rational understanding of etiopathogenesis of the systemic complications arising out of sudden, severe alterations in structure and function of the skin consequent to the syndrome of acute skin failure clearly establishes the necessity of a dedicated ICU in a skin department. Immune suppression due to increased age, organ transplantation, malignancy, prolonged intake of steroids as also the indiscriminate use of drugs have lead to a spurt in the incidence of widespread, recalcitrant dermatoses with significant potential to eventuate into reaction patterns terminating into acute skin failure, viz. universal erythema and scaling of erythroderma and widespread denudations of bullous dermatoses. Prompt intensive management of all such cases in the ICU on the lines of 100% burns is mandatory. PMID- 27407847 TI - Virtual Scopy with Multidetector CT. AB - Virtual scopy is a computerized, non-invasive technique used in simulating views provided by a fiber optic endoscope. Multidetector CT (MDCT) enhances the technique of Virtual scopy, by its z-axis resolution, faster data acquisition and improved 3D-image quality. The common application included Virtual Colonoscopy, Bronchoscopy, Gastroscopy, Angioscopy, Labyrinthoscopy, Thoracoscopy and Stentoscopy. Of the 45 Virtual scopies referred to Radiology Department at INHS Asvini, the single largest application was Virtual Angioscopy followed by Stentoscopy and the smallest was evaluation of larynx, labyrinth, colon and mediastinum accounting for 3 each. Endoscopy data and histopathological diagnosis was available in 17 patients, who underwent Virtual studies of larynx, airway, stomach, mediastinum and colon. PMID- 27407848 TI - A Simple Modification to Boyle's Anaesthesia Machine. PMID- 27407849 TI - Miltefosine: First Oral Drug for Treatment of Visceral Leishmaniasis. PMID- 27407850 TI - Hypomelanosis of Ito. PMID- 27407851 TI - Retrospective Study of Implant Failure in Orthopaedic Surgery. PMID- 27407852 TI - Multiple Fractures in Neonates and Osteogenesis Imperfecta. PMID- 27407853 TI - Angiosarcoma Presenting as Pleuro-pericardial Effusion. PMID- 27407854 TI - Two Cases of Salmonella Splenic Abscess. PMID- 27407855 TI - Negative Bone-scan in Acute Hematogenous Osteomyelitis. PMID- 27407856 TI - Torsion of Wandering Spleen: Diagnosis using Magnetic Resonance Imaging. PMID- 27407857 TI - Berardinelli Seip Syndrome. PMID- 27407858 TI - Periocular Filarial Lymphoedema. PMID- 27407859 TI - Intestinal Duplication Cyst. PMID- 27407860 TI - Management of Congenital Diaphragmatic Hernia. PMID- 27407861 TI - Management of Congenital Diaphragmatic Hernia: Reply. PMID- 27407862 TI - Telemedicine: A user's perspective. PMID- 27407863 TI - Telemedicine: A user's perspective: Reply. PMID- 27407864 TI - Inappropriate Use of Hospital Beds: Reply. PMID- 27407865 TI - Inappropriate Use of Hospital Beds. PMID- 27407866 TI - Armed Forces Medical Services Saw it Coming Two Decades Back! PMID- 27407867 TI - Salmonella Typhi: A Changing Sensitivity Pattern: Reply. PMID- 27407868 TI - Salmonella Typhi: A Changing Sensitivity Pattern. PMID- 27407869 TI - Congenital Muscular Torticollis: A Few Suggestions Regarding Treatment: Reply. PMID- 27407870 TI - Congenital Muscular Torticollis: A Few Suggestions Regarding Treatment. PMID- 27407871 TI - Life After Cancer. PMID- 27407873 TI - Clinical Appraisal of Indigenous Below Knee Endoskeletal Carbon Fibre Prosthesis. AB - BACKGROUND: Amputation is a catastrophe, which results in physical, social, psychological and economic handicap. Provision of suitable prosthesis (artificial limb) is a major step towards rehabilitation of these patients. METHODS: With an aim to provide comfortable, prosthesis to these patients, Artificial Limb Centre (ALC) Pune, developed Below Knee Carbon Fibre Shaft Endo-Skeletal (BK ES CF) Prosthesis in collaboration with DEBEL, Bangalore, a DRDO establishment. 815 Below Knee Amputee patients have been provided with the newly developed Endo skeletal prostheses at ALC Pune till 31 Dec 2003. New BK ESCF prosthesis was evaluated for its performance by feedback received from 500 patients. RESULTS: More than 86% patients were satisfied with the performance of new prosthesis and they achieved almost normal gait. CONCLUSION: The performance of new BK ESCF prostheses was excellent and it achieved good clientele satisfaction. PMID- 27407872 TI - Significance of Tuberculin Testing in HIV Infection: An Indian Perspective. AB - BACKGROUND: Tuberculin skin testing (TST) is a reliable tool in the diagnosis of tuberculous infection and is important in its control. However, it may be false negative in immunocompromised patients like HIV-infected. METHODS: We examined the pattern of TST results in 523 newly diagnosed HIV-positive patients. CD4, CD8 and absolute lymphocyte counts were done by flowcytometry in 63 of these cases. RESULTS: 56 (44.10%), 15 (11.81%) and 56 (44.10%) of the 127 cases with tuberculosis and 293 (73.99%), 41 (10.35%) and 62 (15.66%) of the 396 cases without any clinical evidence of tuberculosis showed TST results of 0-4, 5-9 and = or > 10 mm respectively. Significantly more (P<0.05) number of cases with TST of = or > 10mm and significantly lesser (P<0.05) number of cases with TST of 0-4 mm are likely to develop tuberculosis. The average CD4+lymphocyte count was found to be significantly lower in cases with nil TST results than with = or >10mm. HIV infected cases associated with tuberculosis with induration on TST had average CD4 counts of 129.5 as compared to 246.3/cmm in those without tuberculosis. CONCLUSION: In India where both these diseases are endemic, tuberculosis may develop during early HIV infection, while the body's immunity is still largely unimpaired and TST shows = or >10mm results in almost 45% of our cases. In another 45% with TST of 0-4mm, the CD4+ lymphocyte count is likely to be lower than 200/cmm. In those with nil induration, TST of 5-9 mm cannot be taken as an independent marker for suspecting tuberculosis in the HIV infected. Hence we recommend that all cases with TST of = or >10mm and cases with nil induratrion with CD4+ count of <200/cmm should be considered as high-risk for developing tuberculosis. PMID- 27407875 TI - Safety and Efficacy of Sodium Bicarbonate versus Hyaluronidase in Peribulbar Anaesthesia. AB - BACKGROUND: 400 cases undergoing surgery for cataract under local anaesthesia were studied. Peribulbar anaesthesia involves injecting a mixture of 2% lignocaine, bupivicaine 0.5% and hyaluronidase into the peripheral space of the orbit through a single infero-lateral point. Sodium bicarbonate has been shown to reduce the time of onset of anaesthesia and pain perception when mixed with local anaesthetics. METHODS: This study compared two groups of patients (200 each), one receiving hyaluronidase mixed anaesthetic and the other sodium bicarbonate buffered anaesthetic. The groups were compared for effectiveness of the anaesthesia, its onset, duration and the final visual outcome. RESULTS AND CONCLUSION: Sodium bicarbonate was shown to reduce the time of onset and increase the successful block rate without any adverse affects. PMID- 27407874 TI - Cervical Disc Replacement for Spondylotic Myeloradiculopathy. AB - BACKGROUND: Cervical disc replacement is a newer concept and rapidly developing surgical treatment. A prospective study was conducted to determine, if accurately implanted Bryan's cervical disc prostheses can provide relief from objective neurological symptoms and signs, stability and normal range of motion in cases of cervical disc prolapse with myeloradiculopathy. MATERIAL AND METHOD: Twenty patients underwent Bryan cervical disc replacement from Jan 2002 to Dec 2003. Young patients between age groups 21 to 50 years with degenerative cervical disc prolapse at C3-C7 with myeloradiculopathy were included in this study. Patients with significant facet joint arthropathy, unstable spine, trauma, tumour, osteoporosis and active infection were excluded from this study. Nurick's grading was used for quantifying the neurological deficit. Patients were operated by anterior cervical approach using a specially designed Bryan's cervical discectomy system. Neurological and radiological outcome was assessed post operatively and at 2,6,12 and 24 months follow up. Outcome analysis was carried out using modified Odom's criteria. The radiographic results were assessed by taking antero posterior (AP) and lateral radiographs of cervical spine to find range of motion and device position. RESULTS: The patients were in the age group of 31 to 50 years. There were 14 (70%) male and 6 (30%) female in this study. Neck pain and brachialgia were the presenting symptoms in all cases, 12 (60%) had radiculopathy and 8 (40%) had myelopathy. Single level disc prolapse was present as per Magnetic Resonance Imaging (MRI) in four (20%) at C4-C5, 12 (60%) at C5-C6 and 4 (20%) at C6-C7. Bryan's disc size 15 was used in 8 (40%) and size 17 was used in 12(60%) patients. During post-operative, 02, 06, 12, and 24 months follow up, the clinical outcome was excellent in 16 (80%) and good in 4 (20%) as per modified Odom's criteria. There was demonstrated improvement in flexion, extension and rotation clinically and radiologically during follow up. There was no migration or displacement of device. CONCLUSION: Cervical disc replacement for cervical disc prolapse with myeloradiculopathy represents an exciting new technology. Patients treated with the Bryan cervical disc prosthesis for single level cervical disc prolapse showed good to excellent improvement in neurological deficit. Clinically and radiologically maintenance of motion was found during follow up. More patients with longer follow up and post operative MRI to find out the protection to adjacent discs from abnormal stress will be required before this prosthesis is accepted as a treatment option. PMID- 27407876 TI - Surgical Approach for Polycystic Ovarian Syndrome in Management of Infertility. AB - BACKGROUND: In patients with Polycystic Ovarian Syndrome (PCOS), resolution of infertility is an important goal of treatment. Wedge resection of the ovaries described as a means to achieve this was practiced in the middle of twentieth century. With the advent of endoscopic surgery, surgical approach for the same condition has been modified. Multi point biopsy, multiple needle puncture, electofulguration and laser fulguration are being tried in the context of PCOS. This project was taken up to evaluate the scope of electo fulguration in clomiphene resistant PCOS. METHODS: Forty patients who did not show sonographic evidence of ovulation with clomiphene citrate (CC) 100mg OD for 05 days in two cycles were subjected to laparoscopy. The patients who did not show any pelvic factor for infertility were alternately assigned to electro - fulguration treatment of ovaries or no fulguration during laparoscopy. These were designated as 'Lap EC' & 'Only CC' group respectively. For 'Only CC' group' stimulation with CC was continued for four cycles with a higher dose 150 mg OD for 05 days. Lap EC group were subjected to CC 100mg OD for 5 days for two cycles in case of non achievement of ovulation in the first two drug free cycles following EC. Folliculometry, HCG administration and Intra Uterine Insemination (IUI) was performed for both groups. RESULTS: Total percentage of ovulatory cycles were 51.8% in EC group compared to 5.26% in the CC group. Overall pregnancy rate of 30% was achieved in the Lap EC group as compared to only 10% in the CC group (p<0.05). CONCLUSION: Laparoscopic electrofulguration of ovaries increases the chances of ovulation and conception. This being a cheaper one time procedure as compared to other expensive ovulation inducing agents, should be the preferred mode and the primary procedure wherever polycystic ovaries are encountered while evaluating a case of infertility by laparoscopy. PMID- 27407877 TI - Value of Silver Binding Nucleolar Organiser Regions (AgNOR) in Squamous Cell Carcinomas of Upper Aero-digestive Tract. AB - BACKGROUND: Study of Silver-binding nucleolar organizing regions (AgNORs) in 50 cases of squamous cell carcinomas (SCC) of upper Aero-digestive tract was carried out with an aim of correlating AgNOR positivity with histological grade of tumour and evaluating value of AgNOR staining in predicting the progress of disease. METHODS: Tissue sections of the cases were stained with 50 percent silver nitrate solution for AgNOR evaluation and the data analysed. All the sections were also stained with haematoxylin and eosin stain for tumour typing and grading. RESULTS: In this study, the mean AgNOR (mAgNOR) score of normal squamous epithelium (50 cases) was 1.56 (range1.00-2.80), that of well differentiated squamous carcinoma (27 cases) was 3.29 (range 2.4-4.6), moderately differentiated squamous carcinoma (21 cases) was 4.29 (range 2.7-5.6) and of poorly differentiated squamous cell carcinoma (2 cases) was 5.21. The mAgNOR scores were statistically significant. Comparison of the percentage AgNOR (pAgNOR) scores between well differentiated and moderately differentiated carcinomas showed that all the pAgNOR values (1-9) were significant. However, pAgNOR 3 and pAgNOR 4 were most significant. Cut off values for pAgNOR score to differentiate between the various grades of squamous cell carcinomas could not be calculated due to lack of data on survival rates. CONCLUSION: AgNOR technique can definitely be used as a supportive tool to routinely performed Hemotoxylin and Eosin staining and may help in prognosis as well as therapeutic decision-making in squamous cell carcinomas. Studies of larger number of cases in a prospective study are needed to arrive at more substantial conclusions. PMID- 27407878 TI - A Study of Midtrimester Abortion using Cerviprime Gel and Extra-Amniotic Prostodin. AB - BACKGROUND: A study was carried out to evaluate the efficacy of intra cervical dinoprostone gel and extra-amniotic prostodin in midtrimester abortions. MATERIAL AND METHOD: A total of 25 cases were included in this study. Dinoprotone gel was inserted intracervically in the evening and next morning Inj Prostodin diluted in saline was injected extra amniotically. The efficacy and side effects of the method were studied. RESULTS: The mean induction abortion interval was found to be 17.32 hrs and there were no failures. 04 cases required assistance for removal of placenta. There were no other complications. CONCLUSION: Intra-cervical dinoprostone gel combined with extraamniotic prostodin is an effective and safe method of mid trimester abortion. PMID- 27407879 TI - Preservation of Spinal Accessory Nerve during Radical Neck Dissection. AB - BACKGROUND: Radical Neck Dissection done in cases of squamous carcinoma of the head and neck with cervical metastases leads to significant morbidity due to the 'shoulder syndrome' arising from denervation and atrophy of the trapezius muscle supplied by the Spinal Accessory Nerve (SAN). Preservation of the SAN (described as Modified RND Type 1) has been described by various workers. METHODS: We present our experience with 24 patients of squamous carcinoma of the head and neck with cervical metastases. MRND Type 1 was performed in those cases where the SAN was not involved by metastatic disease. RESULTS: The SAN could be preserved in all the patients who were cN0, cN1 and cN2. Only one patient who was cN3 required sacrifice of SAN as the nerve was infiltrated by metastatic disease. Shoulder function was good where SAN was preserved. Conclusion : This procedure is oncologically safe and morbidity associated with the "Shoulder Syndrome" was prevented. PMID- 27407880 TI - Evaluation of Suspected Monoclonal Gammopathies: Experience in a Tertiary Care Hospital. AB - BACKGROUND: Monoclonal gammopathies occurs in patients with malignant diseases of plasma cells and lymphocytes and in few benign conditions. The objective of this study was to assess the precision, accuracy and confirmation of monoclonal gammopathies on serum protein electrophoresis (SPE) and the clinical relevance of detection and characterization of M component. METHODS: All samples received for serum electrophoresis in the last 3 years were analysed for data on M band positivity and correlating it with clinical profile of the patients. Immunofixation (IFE), Immunoelectrophoresis (IEP) and IgG, IgM estimation were carried out in few cases. The follow up of cases was done by serial monitoring of SPE and beta2 microglobulin levels. RESULTS: 1155 samples were received during the 3 years period. 282 (24.4%) samples were positive for M component on SPE. Of these, 239 (84.8%) patients had M spike in lambda region and 43 patients had M spike in beta region. The mean load of the M protein band in the lambda region was 37.8% and in beta region was 35.8%. IgG with kappa chain was seen in 40%, IgG with lambda chain was seen in 50%, 5% patients each had IgM with kappa and IgA with lambda light chain. 246 samples (96.5%) had high levels of beta2 microglobulin. Of the 116 cases of multiple myeloma, IgG levels was more commonly raised (5%) as compared to IgA (6.9%) and IgM (5.2%). CONCLUSION: It is recommended that SPE should be performed in patients having unexplained weakness, anaemia, back pain, osteoporosis, osteolytic lesions, fractures, renal insufficiency or recurrent infections. PMID- 27407881 TI - Study of 7 Cases of Giant Cell Tumor of Soft Tissue. AB - BACKGROUND: Primary giant cell tumour of soft tissues is a distinct but uncommon group of neoplasms morphologically identical to osseous giant cell tumor. METHODS: 7 patients with painless growing soft tissue mass, having no attachment to underlying bone, were identified in a four years retrospective study from two zonal hospitals of armed forces. Histopathology of these lesions revealed admixture of multinucleated giant cell with mononuclear cells. All patients were treated by surgical resection and followed up for recurrence. Results : There were 5 male and 2 female patients in the age group of 18 to 56 years. All lesions were superficial, circumscribed and involved extremities except one. Histologic transition between benign and malignant lesion was present in only one of the 7 patients that recurred after three months of surgery for which she had to be operated again. 2 of our 7 cases were lost in follow up. CONCLUSION: Primary giant cell tumour of soft tissues usually present as a painless mass and needs to be differentiated from other giant cell rich soft tissue tumors. Benign clinical course is expected if the lesion is excised adequately. Its biological behaviour to have low malignant potential is recognized; but this cannot be predicted and metastasis does occur rarely. PMID- 27407882 TI - Differentials and Determinants of Syndrome 'X' and its Role as Coronary Risk among Healthy Middle Aged Indian Army Personnel. AB - BACKGROUND: Syndrome 'X', a clustering of impaired glucose tolerance (IGT), raised blood pressure, raised serum triglycerides and low HDL-cholesterol, occurring under the influence of insulin resistance and resultant hyperinsulinaemia, has been hypothesised to be a major risk factor for ischaemic heart disease (IHD). However, there is a lack of research based evidence in this field, in our country. METHODS: The study was a cross-sectional analytical epidemiological design of 614 healthy Indian Army personnel, aged 35 years and above, selected by random sampling. RESULTS: The study indicated that there is a statistically significant (p < 0.001) clustering between fasting hyperinsulinaemia, raised blood pressure, IGT, raised triglycerides and low HDL. The prevalence of syndrome 'X' was 8.47% (95% CI 6.27% to 10.47%). Initial univariate and subsequent multivariate analysis using multiple logistic regression method, indicated that predictors of syndrome 'X' were increasing age, overweight, increasing central (abdominal) obesity, lack of adequate physical exercise and low level of physical fitness. Presence of syndrome 'X' increased the risk of resting ECG changes suggestive of coronary insufficiency (OR = 6.29, p < 0.001). CONCLUSION: Based on the findings, recommendations for prevention of this syndrome have been submitted. PMID- 27407883 TI - Norms of the Rorschach Test for Indian Subjects. AB - BACKGROUND: The clinical utility of the Rorschach test in Indians is hampered by the absence of reliable normative data. Method : The Rorschach by Dlopfer's method was administrated to 1256 subjects consisting of 300 normal army personnel, 300 normal civilians, 250 schizophrenics, 300 neurotics and 106 patients with organic disorders. RESULTS: The Rorschach protocols of normal Indian army personnel and normal civilians showed significant differences from one another and also from the western norms. These differences are culturally determined and are not indicative of low intelligence or psychopathology. Patients with schizophrenia, neurosis, head injury and epilepsy show significant differences from the records of normal subjects. The protocols of army schizophrenics show significant deviations from those of normal army personnel and these changes revert to normal with clinical recovery. CONCLUSION: The Rorschach test is not a culture fee test as claimed earlier. In view of the differences from Western norms, Rorschach protocols of Indians should be interpreted using the norms for Indians. In the case of army personnel the norms for army personnel should be used. While the use of the Rorschach to study the personality patterns of normal individuals and as an aid to clinical diagnosis was strongly supported, the findings of the study indicate that the test can also be employed to assess therapeutic response of patients with schizophrenia. PMID- 27407884 TI - Newer Diagnostic Methods in Oncology. PMID- 27407885 TI - Targeted Therapy in Oncology. PMID- 27407886 TI - Leucodepletion and Blood Products. AB - BACKGROUND: Leucoreduction of blood products is increasingly being employed to produce blood products with residual WBCs < 5 * 10(6) per unit (99.9 percent or a log 3 leucoreduction). Clinical data suggests that non-haemolytic febrile transfusion reactions can be prevented by leucodepletion. The procedure also prevents alloimmunisation to HLA antigens in patients who will repeatedly require transfusion of blood/blood products. METHOD: Of the methods available to reduce the number of WBC in blood products washing of red cells, freezing and deglycerolisation are effective and yield a product with only a 24 hour shelf life. Other methods such as leucodepletion filters are relatively inexpensive, simple and the final product has a normal shelf life. Modern generation of leucoreduction filters and apheresis machines can provide greater than 4 log reduction of WBC. RESULTS: After the introduction of leucodepletion of blood for Thalassemics at our center in 2003, the incidence of non haemolytic febrile transfusion reactions (NHFTR) fell from 4% in 2002 to 1% in 2003. CONCLUSION: In patients undergoing long-term blood transfusion therapy e.g. Thalassemics, alloimmunisation against the HLA antigens on donor white cells is prevented by leucodepletion and prevents NHFTRs. PMID- 27407887 TI - Field Adaptable Tests for Kala-Azar. PMID- 27407888 TI - Biomaterial Update in Restorative Dentistry. PMID- 27407889 TI - Anaesthetic Implication of Von Hippel Lindau Disease. PMID- 27407890 TI - Lingual Thyroid. PMID- 27407891 TI - Benign Neonatal Sleep Myoclonus: Is it so Uncommon? PMID- 27407892 TI - Spontaneous Expulsion of Subconjunctival Cysticercus Cellulosae. PMID- 27407893 TI - A Case of Synchronous Renal Cell Carcinoma (Rt) and Transitional Cell Carcinoma Urinary Bladder. PMID- 27407894 TI - Fatal Cerebral Leucostasis in Acute Leukaemia with Hyperleucocytosis. PMID- 27407895 TI - Why do we miss Metastatic Renal Cell Carcinoma? PMID- 27407896 TI - Hypoplasia of Internal Acoustic Meatus. PMID- 27407897 TI - Internal Iliac Artery Embolisation in Post LSCS Haemorrhage. PMID- 27407898 TI - Uterine Didelphys with Pregnancy and Cervical Incompetence. PMID- 27407899 TI - Resuscitation by Intraosseous Infusion in Newborn. PMID- 27407900 TI - Musculoskeletal Imaging: MRI versus Three Dimensional Spiral CT. PMID- 27407901 TI - Musculoskeletal Imaging: MRI versus Three Dimensional Spiral CT: REPLY. PMID- 27407902 TI - Breast Feeding and Antenatal Preparation. PMID- 27407903 TI - Breast Feeding and Antenatal Preparation: REPLY. PMID- 27407904 TI - Surgery in the War-Zone. PMID- 27407905 TI - Damage Control Surgery for Abdominal Trauma. AB - Damage control is not a modern concept, but the application of this approach represents a new paradigm in surgery, borne out of a need to save patients with severe exsanguinating injuries. Definitive control and repair may be accomplished in the immediate post injury setting but the physiological derangement due to massive shock state resulting from the severe injury and the resuscitation that follows, often leads to a fully repaired but dead patient. The vicious triad of death in trauma, namely hypothermia, acidosis and coagulopathy should be tackled by initial abbreviated laparotomy, correction of physiological derangements and finally definitive repair of all injuries at second laparotomy. The concept needs a dedicated team effort with careful patient selection for achieving the optimal results. PMID- 27407906 TI - Abdominal Compartment Pressure Monitoring - A Simple Technique. PMID- 27407907 TI - Toxic Epidermal Necrolysis : A Case Report. PMID- 27407908 TI - Prostatic Cyst : Association with Autosomal Dominant Polycystic Kidney Disease. PMID- 27407909 TI - Diffuse Axonal Injury. PMID- 27407910 TI - Ectopic Decidual Reaction: A Case Report. PMID- 27407911 TI - Abdominal Cocoon. PMID- 27407912 TI - Dieulafoy's Lesion: An uncommon cause of Upper Gastrointestinal Bleeding. PMID- 27407913 TI - Faun Tail Nevus - A Case Report. PMID- 27407914 TI - Tubercular Osteomyelitis of Skull : A Case Report. PMID- 27407915 TI - Endometrial Polypectomy following Medical Dilatation of Cervix. PMID- 27407916 TI - Jeune Syndrome. PMID- 27407917 TI - Partial Hydatidiform Mole - An Unusual Presentation. PMID- 27407918 TI - Lump in a Lactating Breast. PMID- 27407919 TI - Lipoma of the Corpus Callosum : Diagnosis Using Magnetic Resonance Imaging. PMID- 27407920 TI - Hypercoagulable State: Reply. PMID- 27407922 TI - Systemetic Sclerosis with Early Pregnancy. PMID- 27407921 TI - Hypercoagulable State. PMID- 27407923 TI - REPLY. PMID- 27407924 TI - Administration of Mantoux Test in ARMED FORCES MEDICAL SERVICES - Need for Change. PMID- 27407925 TI - Organ Transplantation in India : Indian Scenario and Perspectives for the Armed Forces. PMID- 27407926 TI - Foot Protective System : A Boon to Demining Soldiers. AB - BACKGROUND: A significant number of soldiers suffer serious injuries or die in the process of demining and a protective device is necessary in such operations. METHODS: All the patients involved in demining operations using the foot protection devices in last one year were analysed. RESULTS: We received 35 patients, of which only five had limb injuries and 30 had eye injuries. Of the five, three had closed calcaneal fractures and two contusion of foot. No fatality, amputation or compound fracture occured. CONCLUSION: Early results after the use of this device during demining operations are encouraging. PMID- 27407927 TI - Management of Rh-isoimmunised Pregnancies : Our Experience. AB - BACKGROUND: The aim of this study was to assess the role of middle cerebral artery peak systolic velocity (MCA-PSV), as measured by doppler ultrasound, in detecting foetal anaemia in Rh- isoimmunised pregnancies. Intra-uterine foetal blood transfusion was performed in such anaemic foetuses to tide over the crisis of foetal immaturity till considered fit for extra-uterine survival. METHODS: Rh isoimmunised pregnancies reporting to a tertiary institute from 2003 to 2005, were screened by doppler ultrasound to estimate MCA-PSV to detect foetal anaemia. If the foetus developed MCA-PSV of more than 1.5 multiple of median (MoM) for the gestational age, foetal blood sampling through cordocentesis was performed to confirm foetal anaemia, followed by intrauterine foetal blood transfusion to all anaemic foetuses at the same sitting. Neonatal outcome was evaluated by recording gestational age at the time of delivery, duration of gestational time gained and need for blood transfusion in the neonatal period. RESULTS: A total of thirteen isoimmunised pregnancies were evaluated. Three pregnancies did not require in utero foetal blood transfusion. Twenty-one intrauterine foetal blood transfusions were performed in the remaining ten patients. Five received blood transfusion in the neonatal period. Intra uterine foetal death occurred in one grossly hydropic foetus and favourable neonatal outcome was recorded in the rest. CONCLUSION: The clinical outcome of these pregnancies justifies the use of doppler studies of MCA PSV in detecting foetal anaemia and intra uterine foetal blood transfusion is the only hope of prolonging pregnancy and salvaging such foetuses. PMID- 27407928 TI - Outcome of Dorsal Onlay Buccal Mucosa Substitution Urethroplasty in Long Strictures of Anterior Urethra. AB - BACKGROUND: The surgical treatment of adult anterior urethral strictures is constantly evolving. Controversy exists over the best means of reconstructing the anterior urethra. METHODS: Twelve patients underwent buccal mucosal urethroplasty for long segment anterior urethral stricture between 2003 and 2005 . Eleven patients with a salvageable urethral plate were treated with one stage dorsal onlay urethroplasty, using a perineal or circumcoronal incision. One patient with a severely scarred urethral plate underwent two-stage urethroplasty. RESULTS: At a mean follow up of 14.2 months (range 2 to 26) one (8.3%) patient had short recurrent stricture, which was treated with optical urethrotomy. The mean maximal urine flow rate improved from 8.3 ml/sec to 18.1 ml/sec after the surgery. There were no donor site complications. All patients had a normal slit like meatus and none had chordee or erectile dysfunction. CONCLUSION: In long stricture of anterior urethra, dorsal onlay buccal mucosa urethroplasty provides excellent intermediate term results with a normal, wide caliber urethra. PMID- 27407929 TI - Tracheo-esophageal Puncture (TEP) for Voice Rehabilitation in Laryngectomised Patients Blom-singer(r) Vs Provox(r) Prosthesis : Our Experience. AB - BACKGROUND: Stage III and IV cancers of larynx and hypopharynx often require total laryngectomy which leaves the patient with severe communication handicap. In such laryngectomised patients tracheo-esophageal puncture is the best way for voice rehabilitation using either Blom-Singer(r) prosthesis or Provox(r) indwelling valve. METHODS: A prospective comparative study of Blom-Singer(r) prosthesis and Provox(r) indwelling valves placed in Tracheo-esophageal Punctures (TEP) for voice rehabilitation following total laryngectomy was carried out at the Tata Memorial Hospital, Mumbai and Malignant Diseases Treatment Centre of Armed Forces, to assess their efficacy. This report comprises of our experience in 41 (39 males and two females) laryngtectomees who underwent TEP of which 15 patients were fitted with low pressure Blom-Singer(r) prostheses and 26 with Provox(r) indwelling prostheses. RESULTS: Prostheses related problems like granuloma formation, leakage, candidal growth over the valves and prosthetic decay were significantly less in the patients fitted with Provox(r) prosthesis. Dislodgement of prosthesis with closure of the tract or persistent fistula formation and creation of false passage, while reinsertion were problems encountered in the Blom-Singer group. After three months, speech assessment revealed a better quality of voice production and patient compliance in maintaining the prosthesis in the case of Provox(r) indwelling valve. CONCLUSION: In Indian scenario where illitracy amongst the patients hinders in maintainence of Blom-Singer(r) prosthesis, Provox(r) indwelling value is an appropriate choice for voice rehabilitation. PMID- 27407930 TI - Comparison of Phaconit Rollable IOL with Acrylic Foldable IOL. AB - BACKGROUND: Phaconit or ultra micro incision phacoemulsification cataract surgery involves phacoemulsification through a 0.9 millimetre sleeveless phaco tip and irrigating chopper followed by implantation of a rollable intraocular lens. The procedure leads to negligible astigmatism and faster visual recovery as compared to phacoemulsification with a foldable intraocular lens. METHODS: This prospective study analysed 80 cases of sub millimetre phaconit surgery with implantation of rollable intraocular lenses(IOL) in 40 cases and acrylic foldable IOL in the remaining 40 cases. Evaluation of efficacy and adaptability of procedure, equipment settings, operative constraints, postoperative complications, keratometric and topographic evaluation of induced astigmatism with visual outcome and patient's rehabilitation were studied. RESULTS: The intraoperative complications were surge/ chamber collapse in 16 (20%), iris chaffing in one and corneal burns in two cases. All cases had an induced astigmatism of less than or equal to +/- 0.25 D in four to six weeks after rollable IOL and +/- 0.5 D to +/- 0.75 D after acrylic IOL implantation. All patients had best-corrected visual acuity of 6/6 by third post operative day. CONCLUSION: Phaconit with rollable IOL is a perfect blend of surgical skill, application of technology and ultra thin IOL. PMID- 27407931 TI - Occupational Hazards among Dental Surgeons. AB - BACKGROUND: This study was conducted to assess and increase the level of awareness of occupational hazards among the dental surgeons of Indian Navy. METHODS: The data was obtained using a self-administrated questionnaire from 17 serving dental surgeons that included questions on personal data, awareness of occupational hazards, safety measures practiced and experience of occupational hazard while in practice. RESULTS: All the respondents were aware of the occupational hazards at workplace and had been vaccinated against Hepatitis B infection. 82.3% had regular exposure to dental amalgam. Backache was the commonest hazard in 70.59% members of the study. CONCLUSION: This study shows that although there appears to be a high level of awareness of exposure to occupational hazards among the dental surgeons of the Indian Navy, the practical steps to prevent them needs to be reinforced. Increased awareness must be created about the dangers of chronic mercury poisoning, its prevention, the importance of regular monitoring of blood mercury levels and the mercury vapour levels in the clinic. PMID- 27407932 TI - Flexible Bronchoscopy in the Evaluation of Mediastinal and Hilar Lymphadenopathy. AB - BACKGROUND: The diagnosis in cases of mediastinal and/or hilar lymphadenopathy with no lung parenchymal involvement is often difficult. We undertook this study to assess the diagnostic value of flexible bronchoscopy (FOB) especially transbronchial needle aspiration (TBNA) and transbronchial lung biopsy (TBLB) in these patients. METHODS: Forty eight patients with hilar and/or mediastinal lymphadenopathy without any parenchymal lung lesions, managed between 2000 to 2004 at a tertiary care centre who underwent FOB were evaluated retrospectively. RESULTS: Out of 48 patients, FOB showed widening of carina in six, widening of secondary carina in four, bulge in airways because of extrinsic compression in seven and endobronchial nodule in two patients. It was normal in rest 29 patients. TBNA was done in all patients and TBLB in 13 patients where clinico radiologic findings were consistent with stage 1 sarcoidosis. FOB established diagnosis in 18 patients (caseating granuloma in eight, noncaseating granuloma in nine, and AFB culture positive in one). It was inconclusive in other patients. One patient developed pneumothorax requiring intercostal tube drainage. CONCLUSION: FOB especially TBNA has an important role in the diagnosis of hilar and mediastinal lymphadenopathy and should be considered before other invasive procedures. PMID- 27407933 TI - A Survey of Deaf Mutes. AB - BACKGROUND: Detection of hearing loss at birth or early childhood is difficult. This bears on the rehabilitation of the child as the golden period of learning is lost. Reliable statistics relating the average age for detection of hearing loss and fitting of hearing aids in children are not available in our country. A survey of 52 deaf mutes was therefore conducted to ascertain the probable causes that lead to deafness. METHODS: The study subjects were 42 deaf mutes from the Government run school for deaf mutes and 10 from ASHA School run by the Army Wives Welfare Association. A questionnaire prepared in Hindi was filled by the parents and data analysed. RESULTS: The average age of detection of hearing loss was 2.8 years and the average age for receiving a hearing aid was 7.6 years. Thus due to the significant reduction of sensory input at the 'golden period of learning' only 50% of those fitted with a hearing aid found it useful. In 42.3% the cause of deafness could not be identified. CONCLUSION: Greater emphasis is required on early diagnosis of childhood deafness and fitment of hearing aid. PMID- 27407934 TI - Management of Combat Related Vascular Injuries in a Zonal Hospital. AB - BACKGROUND: The extremity gunshot wound (GSW) and penetrating splinter injuries from mine blast present a surgical challenge in the treatment of arterial trauma especially at non-vascular surgery centre. Adherence to specific principles of management is required for optimal limb salvage. METHODS: Fourteen vascular injuries in patients of GSW and mine explosions were managed at a zonal military hospital with successful outcome in two years. The diagnosis of arterial injury was done clinically. RESULTS: The commonest site of vascular injury was femoral. The methods of choice for repair were autogenous vein interposition or end-to-end anastomosis. All except for two patients retained a functional limb. CONCLUSION: All surgeons in peripheral hospitals should be trained in vascular injury repair to save life and limb. Our series shows that right timing and prompt treatment of vascular injuries in a peripheral hospital, can give satisfactory results. PMID- 27407935 TI - Uterine Balloon Therapy : An Alternative Therapy for Menorrhagia. AB - BACKGROUND: Menorrhagia is a common problem in women of reproductive age. Its aetiology in the absence of organic pathology, hormonal or haematological disorders remains largely unknown. Traditional medical therapy may not be beneficial in the long run. Hysterectomy for this condition is an invasive over treatment. First generation endometrium ablation techniques aimed at destroying the endometrium, were associated with life threatening complications. The second generation endometrial ablation techniques like uterine thermal balloon therapy have reduced these problems. METHODS: Fifty patients were selected for the procedure between 2002 and 2005. The patients qualified for the procedure if they had completed their family, had normal pelvic ultrasound findings, benign endometrial histology, normal PAP smear and clinically a normal size or bulky uterus. RESULTS: 50% patients were in the age group of 35-45 years. 28(56%) procedures were done under local anaesthesia and 22(44%) under general anaesthesia. The patients were followed up for a period of 3 to 29 months (median 16 months). Seven(14%) had amenorrhoea and 40(80%) had normal periods or hypomenorrhoea. Three(6%) patients continued to have menorrhagia and were considered failures. 94% patients were satisfied with the procedure and there were no complications in this series. Conclusions : Uterine balloon therapy is a simple, safe and effective method for the treatment of menorrhagia in selected patients. PMID- 27407936 TI - A Prospective Randomized Controlled Study of Lichtenstein's Tension Free versus Modified Bassini Repair in the Management of Groin Hernias. AB - BACKGROUND: Bassini's repair and the Lichtenstein's tension free mesh hernioplasty are commonly used hernia repair techniques. A prospective randomized controlled study of Lichtenstein's tension free versus modified Bassini repair in the management of groin hernias was undertaken to compare the technique and postoperative course in the two procedures. METHODS: A prospective study was conducted on patients reporting to Command Hospital (SC) Pune with inguinal hernia. One hundred and ninety six patients were included in the study, operated upon by either of technique and followed up. RESULTS: Study involved 196 patients with 216 primary inguinal hernias, studied over a period of 24 months. A total of 118 Bassini repair and 98 Lichtenstein's repair were done. Of the 196 patients, four were females. Bassini Repair took more time than Lichtenstein's repair, though the difference was not statistically significant (p>0.05). Direct hernias took lesser time to operate than the indirect hernias. Pain on the operative day, in the evening, was similar in both the groups. The commonest complication in both the groups was scar tenderness followed by erythema, scrotal swelling, neuralgia, superficial wound infection, funiculitis and seroma formation in the order of frequency. The average hospital stay was 5.74 days for Bassini's repair as compared to 4.97 days for Lichtenstein's repair. Patients undergoing Bassini's repair took longer (mean 28.4 days) to return to work as compared to those who underwent Lichtenstein's repair (mean 21.4 days) and the difference was statistically significant (p < 0.05). The recurrence rate was similar in Bassini's (6.78%) and Lichtenstein's repair (5.10%). CONCLUSION: The Lichtenstein's tension free mesh hernioplasty was comparatively better than modified Bassini's repair due to its simplicity, less dissection and early ambulation in the postoperative period. Surgeons in training found the technique easier to master than the Bassini's repair. PMID- 27407937 TI - Walking Epidural : An Effective Method of Labour Pain Relief. AB - BACKGROUND: Labour pain can be deleterious for mother and baby. Epidural analgesia relieves labour pains effectively with minimal maternal and foetal side effects. A prospective open label study was undertaken to ascertain effective dosing regime for walking epidural in labour. METHODS: Fifty women with singleton foetus in vertex position were included. Epidural catheter was inserted in L2-3 / L3-4 interspinous space. Initial bolus of 10 ml (0.1% bupivacaine and 0.0002% fentanyl) solution was injected and after the efficacy of block was established, an epidural infusion of the same drug solution was started at the rate of 5 ml/hour. RESULTS: In first stage of labour 80% of the parturient had excellent to good pain relief (visual analogue scale 1 to 3) with standard protocol while 20% parturient required one or more additional boluses. For the second stage, pain relief was good to fair (VAS 4-6) for most of the parturient. The incidence of caesarian section was 4% and 6% needed assisted delivery. No major side effects were observed. CONCLUSION: 0.1% bupivacaine with 0.0002% fentanyl maximizes labour pain relief and minimizes side effects. PMID- 27407938 TI - Holmium : YAG Laser for Intra Corporeal Lithotripsy. PMID- 27407939 TI - Severe Acute Respiratory Syndrome : An Update. PMID- 27407940 TI - Conservative Management of Chronic Renal Failure. PMID- 27407941 TI - Focused Abdominal Sonography in Trauma (FAST). PMID- 27407942 TI - Bleeding in Early Pregnancy. PMID- 27407943 TI - A Case of Adenoid Cystic Carcinoma Parotid with Perineural Spread. PMID- 27407944 TI - Vesicovaginal Fistula : A New Treatment Modality. PMID- 27407945 TI - Subcutaneous Emphysema : An Unusual Presentation of Foreign Body Bronchus. PMID- 27407947 TI - Rupture of Rudimentary Horn Pregnancy. PMID- 27407946 TI - An Interesting Case of Intestinal Obstruction. PMID- 27407948 TI - Rare Presentation of an Intrathoracic Goiter. PMID- 27407949 TI - Intraabdominal lymphangioma : A Case Report. PMID- 27407950 TI - Unusual Complication of Ventriculoperitoneal Shunt: Anal Extrusion. PMID- 27407951 TI - Management of Bilateral Condylar Fractures:Case Review. PMID- 27407952 TI - Antenatal Sonographic Detection of Holoprosencephaly. PMID- 27407953 TI - Recurrent Molar Pregnancy. PMID- 27407954 TI - Spontaneous Rupture of Bladder : A Rare Clinical Entity. PMID- 27407955 TI - Syndrome 'X' - Reflection of an 'Endangered Gender'? PMID- 27407956 TI - Syndrome 'X' - Reflection of an 'Endangered Gender'?: Reply. PMID- 27407957 TI - New Technologies: Should we Embrace them so Fast? PMID- 27407958 TI - New Technologies: Should we Embrace them so Fast?: Reply. PMID- 27407959 TI - Malaria: Continues to be a Scourge. PMID- 27407960 TI - Does Schizophrenia Exist? PMID- 27407961 TI - Renal Transplantation - An Experience of 500 Patients. AB - BACKGROUND: Renal transplantation is the treatment modality of choice for patients with end stage kidney failure. We present our experience of graft and patient survival of initial 500 renal transplants performed between May 1991 and July 2006, at Army Hospital (R&R). MATERIAL AND METHODS: All patients received triple drug immunosuppression with cyclosporine/tacrolimus, azathioprine/ mycophenolate mofetil and steroids. Patients in high risk group received induction therapy with IL-2 receptor blockers/anti-thymocyte globulin. RESULTS: Majority of the recipients (79%) were males, whereas majority of the donors (59.4%) were females. In the donor profile, 385 (77%) transplants were live related, 108 (21.6 %) were spousal and 7 (1.4%) were cadaveric transplants. Mean age of the donors and recipients was 42.11 +/- 11.53 years (range 19-72 years) and 33 +/- 9.39 years (range 5-60 years) respectively. Eighty two patients (16.4%) were lost to follow up and the present data on rejections, patients and graft survival pertains to 418 patients. These patients have been followed up for a mean period of 2.63 years (SE, 0.122; median 1.8 years; range 0-13.36 years). Acute rejection episodes occurred in 115 (27.3%) patients and 95% of these could be reversed with steroids/ATG. Sixty eight patients (16%) have died on follow-up. Our one-year, 5 year and 10 year estimated graft survival is 95.4% (SE, 0.01), 80.5% (SE, 0.03) and 53.1% (SE, 0.09) respectively and patient survival at one year is 93.2% (SE, 0.01). The estimated graft and patient survival in our series is 9.83 (95% CI, 8.92-10.73) and 9.80 (8.93-10.67) years respectively. CONCLUSION: This centre's short-term graft survival of 95.4% is comparable to the best centres of the world. PMID- 27407962 TI - Malaria on the Move : Ecological Considerations for the Armed Forces. AB - BACKGROUND: Armed forces personnel deployed in the North Eastern states of India are vulnerable to falciparum malaria. This vulnerability increases during mobilization of troops. METHODS: Epidemiological case sheet was used for recording individual movement, clinical features and laboratory investigations of each case of malaria. Immunochromotography test (ICT) or Paracheck Pf was used as a rapid test for falciparum malaria at the regimental aid post (RAP). Subsequently, a case control approach was used to ascertain whether the cases of malaria differed significantly from healthy controls in observing antimalaria measures such as the use of mosquito nets, repellants and chemoprophylaxis. RESULT: Nineteen out of 623 soldiers suffered from falciparum malaria during a short period of ten days during operational mobilization. Use of mosquito nets and repellants was significantly less among the cases as compared to healthy controls. There was no significant difference among the two groups regarding compliance with chemoprophylaxis. CONCLUSION: A paradigm of "malaria on the move" or "operational malaria" has been proposed. PMID- 27407963 TI - Non Surgical Management of Pseudoaneurysms. AB - BACKGROUND: The incidence of pseudoaneurysm has increased due to the large number of vascular procedures performed and the widespread use of anticoagulation therapy during procedures. Non-invasive methods for management of pseudoaneurysms comprise of ultrasound guided compression (USGC), thrombin therapy, arterial embolisation and endovascular stent graft insertion. We discuss our experience in the management of fourteen cases of pseudoaneurysms using non surgical techniques. METHODS: During a two year period, fourteen patients presenting with pseudoaneurysms of different regions were treated. RESULT: Of the fourteen patients, eleven were iatrogenic and three were attributable to trauma. There were six cases of pseudoaneurysms of the femoral artery following coronary angiography studies. One patient developed pseudoaneurysm of right popliteal artery after external fixation of fracture right tibia and fibula. Three cases of renal artery pseudoaneurysms occurred following percutaneous nephrolithotomy (PCNL). The cases were evaluated using a varying combination of color doppler, multidetector computerised tomography (CT) and angiography. These cases were treated with ultrasound guided compression (USGC), stent graft and coil embolisation. The selection of method was based on the location and size of pseudoaneurysms besides the efficacy of the technique. USGC was performed in seven, of which six were in the femoral artery and one supraorbital. The technique was unsuccessful in three of the seven, wherein stent graft was deployed in the femoral artery. Coil embolisation was utilised in three cases of renal artery pseudoaneurysms following PCNL. CONCLUSION: Follow up with color doppler and CT angiography within a week, 6 and 12 months period showed successful regression of pseudoaneurysms in all cases. PMID- 27407964 TI - Efficacy of Deltamethrin and Cyfluthrin Impregnated Cloth over Uniform against Mosquito Bites. AB - BACKGROUND: The difficulty with insecticide treated mosquito nets is that in military operation, it may not be practical for the personnel to carry mosquito nets with them. In mobile military operations, availability of pre-treated 'patches of cloth' or 'bands', which can be applied over the uniform at strategic sites, could be a feasible alternative. METHODS: A double blind randomised controlled trial was undertaken among troops deployed in counter-insurgency operations in the northeastern parts of the country, to assess the efficacy of synthetic pyrethroid pretreated patches in reducing man mosquito contact, as compared to conventional repellents. RESULT: The study indicated that pretreated patches, when affixed over the uniform, provided significantly higher protection from mosquito bites, when used in addition to the conventional repellents. CONCLUSION: The study recommends that synthetic pyrethroid treated patches be made available to troops operating in highly malarious areas. PMID- 27407965 TI - Reconstruction of Complex Abdominal Wall Defects. AB - INTRODUCTION: Reconstruction of large abdominal wall defects not amenable to primary closure remains a challenging problem. These defects result from trauma, previous surgery, infection and tumour resection. The primary objectives of abdominal wall reconstructions are to protect abdominal contents and provide functional support. The abdominal wall reconstruction aims at providing basic component parts, i.e. skin, soft tissue and fascia. For large soft tissue defects, pedicled or free flap closure can be used. In clean wounds, fascial replacement is accomplished with synthetic mesh provided there is adequate soft tissue coverage. METHODS: We treated a total of 20 consecutive patients with complex abdominal wall defects utilizing various reconstructive procedures. There were 15 males (75%) and 5 females (25%). The aetiology included dehiscence of laparotomy wounds in eight (40%), following ablative surgery for malignant tumours in seven (35%), trauma in three (15%) and congenital defects in two (10%) cases. The reconstructive procedures consisted of onlay prolene mesh in seven (35%), Gore-Tex (PTFE) dual mesh both as inlay and onlay in five (25%), facial partition release technique in three (15%), inlay prolene mesh covered with omentum and split skin graft in two (10%), inlay prolene mesh covered with expanded skin in two (10%), and Gore-Tex dual mesh covered with latissimus dorsi myocutaneous flap in one (5%) case. Postoperatively none developed mesh infection or extrusion. Three patients with malignant aetiology received postoperative radiotherapy. During follow up, one patient developed ventral hernia cephalad to the repair and one died due to recurrence of abdominal wall malignancy. CONCLUSION: The reconstruction of an abdominal wall defect requires a comprehensive plan of preoperative and post operative care of the patient and aims toward restoration of abdominal structural integrity by a variety of procedures. The use of new biomaterials and tissue expanders provides reliable and durable abdominal wall closure along with good aesthetic results. PMID- 27407966 TI - Immunochromatographic Methods in Malaria Diagnosis. AB - BACKGROUND: Malaria remains a major cause of morbidity and mortality in India. This study was carried out to evaluate the use of parasite lactate dehydrogenase (pLDH) test in diagnosis of malaria. METHODS: Blood slides of 400 patients who presented with fever including 104 patients with clinical features suggestive of malaria were studied. The results were compared with microscopy and another immunochromatography test (ICT) based on detection of histidine rich protein-2 antigen [Pfhrp-2] secreted by Plasmodium falciparum. RESULT: In this study the sensitivity and specificity for detection of Plasmodium vivax was 100% while for Plasmodium falciparum the values were 96% and 100% respectively. CONCLUSION: ICT is useful for diagnosis of malaria caused by Plasmodium falciparum in field but microscopy of a well-prepared blood smear must not be omitted in a laboratory setting. PMID- 27407967 TI - An Outbreak of Food Poisoning in a Military Establishment. AB - BACKGROUND: An outbreak of food poisoning in a military establishment mess was investigated and remedial measures suggested. METHODS: A total of 391 persons had consumed meals in the mess on the day of the outbreak. A detailed food history was taken from available persons and the attack rates of each specific food items were calculated with the relative risks. RESULTS: Of the 391 persons who had consumed meals at the mess, 123 were affected giving an overall attack rate of 31.5%. Majority of the cases had loose motions, fever, pain abdomen and vomiting. The maximum attack rate (65.1%) was for those who had eaten chicken preparation. The relative risk was also highest for those who had eaten chicken at lunch on the day of the outbreak (RR - 33.21, 95% CI 8.39 to 131.53). The mean incubation period was 19.73 hours (range 6 - 57 hours). The median incubation period was 18 hours. Bacteriological confirmation was not successful. CONCLUSION: The chicken dish was the epidemiologically incriminating food item responsible for the outbreak. Clinical and epidemiological features were suggestive of salmonella food poisoning. However, same could not be confirmed bacteriologically. PMID- 27407968 TI - Breast Feeding Practices among Families of Armed Forces Personnel in a Large Cantonment. AB - BACKGROUND: There seems to be a gap in the available literature and scientific knowledge about breast-feeding practices among families of armed forces personnel in our country, which needs to be studied. METHODS: A cross sectional epidemiological study design was undertaken on a randomly selected sample of 175 families of armed forces personnel staying in a large cantonment and having at least one child in the age group of 3-24 months. RESULT: The study observed positive association between various breast feeding practices such as feeding colostrum, demand/scheduled feeding, exclusive breast feeding for 4-6 months, partial breast feeding for 6 - 18 months and various sociodemographic variables such as age, religion, socio-economic status of mother (military rank of husband), parity and place of residence of the mother (where childhood was spent). CONCLUSION: Higher proportion of mothers feeding colostrum was observed because of better educational status of mothers and organized health education activities available to the families of armed forces personnel. Majority (89.14%) gave demand feed and only 10.86% gave scheduled feed. On the other hand a relatively smaller percentage (47.43% and 29.32%) followed the correct practice about duration of exclusive and partial breast-feeding respectively. PMID- 27407969 TI - Psychological Well-being of Medical Students. AB - BACKGROUND: Training in medicine is emotionally demanding. Psychological well being of medical students is a matter of concern. There is lack of Indian studies in this area. METHODS: A total of 105 medical student of one batch were assessed utilizing psychophysiological state inventory, Institute for personality and ability testing (IPAT) anxiety and depression scale, achievement motivation scale, scale for locus of control and 16 PF in three phases at one-year intervals. RESULT: Majority of the students had average achievement, motivation and adaptability. Anxiety and depression scores fell within normal limits. In personality profile factor 'B', 'M' and 'Q41' had changed significantly. Achievement motivation showed significant decreases and CSS1 and PO1 scores showed significant increase during the years of medical education. CONCLUSION: The results demonstrate that over satisfaction and relaxed attitude may have poor academic outcome. PMID- 27407970 TI - Outbreak of Rubella Among Cadets in an Academy. AB - BACKGROUND: Rubella is traditionally considered a childhood disease, but has the potential to cause outbreaks in closed community of young adults. The present paper describes one such outbreak in a military training establishment. METHOD: The cases of rubella outbreak were identified by clinical features (fever, rash and lymphadenopathy) and confirmed by detection of high titre of anti-rubella IgM antibodies by enzyme-linked immunosorbent assay. Initial serum samples were also tested for antibodies against measles, scrub typhus and dengue. Salient epidemiological features of the outbreak were studied. RESULT: 163 cadets were admitted in the local military hospital within two months. The cases presented with fever, coryza, lymphadenopathy and maculopapular rash. 117 (71.78%) of the samples showed presence of anti-rubella IgM antibodies. CONCLUSION: Rubella outbreaks in military communities have the potential to adversely affect military training/operations. The need for administration of vaccination against rubella in such population may be reviewed. PMID- 27407971 TI - Psychiatric Morbidity Pattern in a Child Guidance Clinic. AB - BACKGROUND: There is a paucity of Indian studies on psychiatric morbidity in children. Present work was undertaken in a child guidance clinic in armed forces. METHODS: Retrospective analysis of 213 patients who attended a child guidance clinic was done. RESULTS: Majority (n=138) were boys. 55.9% were referred from paediatric outpatient department while medical officers in periphery referred 38.5%. The diagnoses was mental retardation in 30.97%, behavioral and emotional disorders in 23.06% and neurotic, stress related and somatoform disorders in 15.98% cases. PMID- 27407972 TI - Malaria in Pregnancy. AB - BACKGROUND: Malaria in pregnancy contributes to low birth weight and increased infant mortality. METHODS: The study included 416 pregnant women reporting with fever and the impact of malaria on pregnancy was assessed. RESULT: The study revealed that the protozoal infection affects second trimester more commonly. It increases the chances of abortions, intrapartum foetal distress and meconium stained amniotic fluid. CONCLUSION: Malaria is an important cause of feto maternal morbidity during pregnancy. PMID- 27407973 TI - Controlled FiO2 Therapy to Neonates by Oxygenhood in the Absence of Oxygen Analyzer. AB - BACKGROUND: A study was conducted to evaluate a system of standardizing the oxygen concentration inside the oxygen hood and to develop guidelines for controlled FiO2 administration by changing size of the hood, lid position on the hood and the oxygen flow rate, without an oxygen analyzer. The effect of low flow rates on carbon dioxide (CO2) retention was also studied. METHOD: A dummy patient and thirty neonates, requiring oxygen to be delivered through head box, constituted the material for the study group. Oxygen content in the head box was measured using a standard oxygen analyzer while the size of head box, flow rate and lid position were changed independently and in combination. The head boxes were tested on a dummy patient. These results were analyzed, and applied to thirty neonates requiring oxygen therapy using a head box. RESULT: Volume of headbox had an inverse relation with the oxygen concentration inside the headbox and smaller sized headbox achieved more predictable oxygen concentration at all flow rates. Maximum difference in oxygen concentration by varying the lid position was seen in the large headbox. Keeping the variables constant, oxygen concentration was significantly lower in babies as compared to dummy. No significant CO2 retention was found at a flow rate of four litres per minute (lpm) in small and three lpm in a medium and large head box respectively, while lower flow rates were associated with CO2 retention. CONCLUSION: It is possible to predict the oxygen concentration inside the head box without the use of oxygen analyzer. Larger head box and higher lid position, results in lower oxygen concentration, at a given oxygen flow rate. Oxygen concentration achieved in babies is lesser than the concentration achieved in a dummy. Flow rates of less than four lpm in small and three lpm in medium and large sized head boxes are associated with CO2 retention. These results are not applicable to infants weighing less than 2 kg. PMID- 27407974 TI - Occupational Stress in Naval Personnel. AB - INTRODUCTION: Increased stress levels have been reported and it has been implicated for mental illness amongst service personnel. However no study has been reported among Indian naval sailors. METHODS: Occupational stress and life satisfaction was measured in 413 naval personnel serving afloat and ashore. RESULT: Naval personnel serving on board submarine and ship had lower levels of occupational stress as compared to those serving on shore establishments. Occupational stress scores were higher among junior sailors (36.7%) as compared to officers and senior sailors (20%). Life satisfaction scores were lower in junior sailors. Greater occupational stress was linked to lower life satisfaction. CONCLUSION: The findings of high occupational stress in junior sailors needs to be investigated further with a larger sample. PMID- 27407975 TI - Injuries due to Landmine Blast Referred to Shahid Motahhary Hospital, Iran. AB - BACKGROUND: The health system faced a new problem of an increasing number of civilian victims of landmine explosions at the end of Iran-Iraq war. METHODS: In a descriptive survey from 1998 to 2004, data was collected retrospectively from medical records of Shahid Motahhary Hospital, Urmia University of Medical Sciences, Iran. RESULT: The study covered 156 victims. 80% of the casualties were civilians of which 95% were male. Injuries led to amputation in 73.3% of the victims. The mortality rate was 3.8%. Blood transfusions was given to 93 (62%) victims. There were 52.6% pattern I, 14.6% pattern II and 32.6% pattern III injuries according to International Committee of the Red Cross (ICRC) classification. CONCLUSION: Mine awareness programs should be conducted amongst civilians who live in high-risk areas. Improved health infrastructure with trained personals for emergency care and early transfer of the casualties would reduce morbidity and mortality. Studies are required to understand the social and public health consequences of this problem. PMID- 27407976 TI - Changing Pattern of Alcohol Abuse in the Army before and after AO 3&11/2001. AB - BACKGROUND: The Army Order 3&11/2001 was introduced to curb alcoholism and to weed out habitual alcoholics. Hence a study was carried out in a zonal referral hospital from 01 Jan 2001 to 30 Jun 2003 to assess its effectiveness. METHODS: The subjects consisted of officers, junior commisioned officers and other ranks who satisfied the International Classification of Diseases (ICD) 10 criteria for alcohol dependence. RESULT: Out of 1023 consecutive admissions, alcohol dependent cases numbered 245 (23.95%). They were disposed as under: 57/ 245 (23.6%) in S1 (fit for all duties), 67/245 (27.35%) in S2 (fit for duties with few restrictions), 72/245 (29.39%) in S3 (fit for duties with more restrictions), and 32/245 (13.06%) in S5 (unfit for further service.). CONCLUSION: The data showed that the percentage of cases disposed under fit for all duties had risen four times (23.80 vs 5.86), those invalided out increased by two times (12.70 vs 6.64) and those retained in S2 had reduced (26.46 vs 41.21) after the new policy. PMID- 27407977 TI - Informed Consent. AB - There have been significant changes in the doctor patient relationship with the impact of technology in day-to-day practice. More and more patients are aware of their rights and are keen to make free choice and decision on their treatment. This helps them to choose the treatment of their choice from the options available and to select a physician of their choice. Doctor's decisions are being questioned regarding their correctness and there is a need to educate the patient, on what one offers by way of treatment. In some procedures and types of treatment, patient needs to be educated and informed of the merits and demerits of the treatment available. This will help the patient to make appropriate choice and also to accept some adverse outcome of treatment. Towards this end, all countries are looking afresh at the necessity of Informed Consent. Methods adopted by some countries are highlighted to help our physicians practice them in an appropriate way. A lot of remedial work needs to be done to minimize future litigation, as many doctors misunderstand their legal obligations and haven't caught up with the change in judge's thinking. PMID- 27407978 TI - Combination Vaccines. AB - Infections are still a leading cause of morbidity and mortality in children under five years of age, most of which can be prevented by vaccination. However, there are too many vaccines to be administered, increasing the cost of immunization and visits to the paediatrician. Combination vaccines can be an answer to these problems till the development of a single vaccine containing all the possible antigens. Researchers are aiming at development of an ideal vaccine, which can be given orally at birth, has negligible side effects, is heat stable and is affordable to all the parents. PMID- 27407979 TI - Medical Negligence in Military Hospitals. AB - BACKGROUND: Bringing the doctors under the ambit of Consumer Protection Act has made an impact on doctor-patient relationship. There has been an increase in legal cases of medical negligence in the recent past. This article provides practical information on medical negligence. METHODS: Complaints received at Army Headquarters were studied to understand the factors involved in medical negligence. RESULT: Various aspects of medical negligence including doctor patient relationship in the military set up have been discussed. Preliminary measures to be taken to avoid cases of negligence are enumerated. CONCLUSION: Good communication skills to build a rapport with the patient is the key to avoid majority of the complaints. The doctor must pay due courtesy, respect and care to the patient besides maintaining medical records scrupulously. PMID- 27407980 TI - A Modification for Oxygen Delivery to Intensive Care Unit Ventilator. PMID- 27407981 TI - Caudal Regression Syndrome. PMID- 27407982 TI - Tumoral Calcinosis. PMID- 27407983 TI - Hepatitis - A induced Non Infantile Giant Cell Hepatitis. PMID- 27407984 TI - Discoid Lupus Erythematosus leading to Squamous Cell Carcinoma. PMID- 27407985 TI - Multicentric Tubercular Dactylitis. PMID- 27407986 TI - Cutaneous T-Cell Lymphoma (Mycosis Fungoides). PMID- 27407987 TI - Multifocal Pyomyositis. PMID- 27407988 TI - Endemic Hemoptysis. PMID- 27407989 TI - Post Herpetic Spinal Segmental Paralysis. PMID- 27407990 TI - Paraesophageal Bronchogenic Cyst. PMID- 27407991 TI - A Case of Secretory Glomus Jugulare. PMID- 27407992 TI - A Case of Nosocomial Atypical Mycobacterial Infection. PMID- 27407993 TI - Prospective Medical Studies in the Armed Forces. PMID- 27407994 TI - Transfusion Transmitted Infections in Armed Forces: Prevalence and Trends - Reply. PMID- 27407995 TI - Transfusion Transmitted Infections in Armed Forces: Prevalence and Trends. PMID- 27407996 TI - The Polymeal: A Natural, Safer and Probably Tastier Strategy to Reduce Cardiovascular Disease (Journal Scan) - Reply. PMID- 27407997 TI - The Polymeal: A Natural, Safer and Probably Tastier Strategy to Reduce Cardiovascular Disease (Journal Scan). PMID- 27407998 TI - What's in a Name? PMID- 27407999 TI - Reemergence of Chloramphenicol Sensitivity in Enteric Fever. AB - BACKGROUND: Enteric fever is a global health problem and rapidly developing resistance to various drugs makes the situation more alarming. Drug sensitivity in Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A isolated from 45 blood culture positive cases of enteric fever was tested to determine in-vitro susceptibility pattern of prevalent strains in northern India. METHODS: Strains isolated from 45 blood culture positive cases of typhoid and paratyphoid fever over a period of three years were studied and their sensitivity patterns to chloramphenicol, ampicillin, ciprofloxacin, ceftriaxone, nalidixic acid, amikacin and ofloxacin were analysed. RESULTS: Our results show a high sensitivity of both Salmonella enterica serovar typhi (96%) and Salmonella enterica serovar paratyphi A (100%) to chloramphenicol. Sensitivity to ciprofloxacin and amikacin was 88% and 84% respectively. All the isolates were sensitive to ofloxacin, nalidixic acid and ceftriaxone. Sensitivity of Salmonella enterica serovar paratyphi A was 100% to chloramphenicol, ciprofloxacin, ofloxacin, nalidixic acid and ceftriaxone, 95% to amikacin and 30% to ampicillin. Overall 44 out of 45 isolates of Salmonellae were sensitive to chloramphenicol. CONCLUSION: These findings suggest changing pattern of antibiotic resistance in enteric fever with reemergence of chloramphenicol sensitivity in northern India. PMID- 27408000 TI - Computed Tomographic Findings in 50 Cases of Gall Bladder Carcinoma. AB - BACKGROUND: A retrospective assessment of contrast enhanced computed tomography (CECT) scan findings in histopathologically proven cases of carcinoma of the gallbladder (GB) was performed to review its role in diagnosis, staging and assessment of surgical resectability. METHODS: All the patients had been subjected to a standardised abdominal helical computed tomography scan. Orally administered iodinated contrast was used for opacification of bowel and dynamic intravenous injection of non-ionic iodinated contrast for studying the lesional enhancement and vascular structures. RESULTS: The presence of focal or diffuse mass lesions in the gallbladder fossa, infiltration of a liver and second part of duodenum were the most reliable diagnostic features in carcinoma gallbladder. Regional spread was better delineated on CT scan as compared with ultrasonography. CONCLUSION: CT scan is an effective method for evaluating, characterizing and detecting the spread of GB carcinomas. PMID- 27408001 TI - An Initial Experience of Continuous Peritoneal Dialysis in Children in the Armed Forces. AB - BACKGROUND: Continuous peritoneal dialysis (CPD) is a modality of renal replacement therapy in children with renal failure. A retrospective study analysis of CPD data over four years at our center was carried out. METHODS: Ten children with renal failure on CPD were included. Depending on the supply, peritoneal dialysis (PD) fluids of two different brands were used in the same patients over time. The patient months of CPD were divided into two groups based on the brand of PD fluid used. The rates of complications with the two different fluid brands were compared. RESULTS: The mean age of our patients was 8.8 +/- 2.51 years (range 4 - 13), with a total of 141 patient months of CPD. The mean follow up period was 13.6 months (range 1- 48). The commonest underlying renal pathology was focal segmental glomerulosclerosis in 30%, followed by cresentric glomerulonephritis in 20%. Peritonitis rate was 0.48 episodes per patient year. Patients in Group I had one episode of peritonitis per 53.5 patient months and Group II had one episode per 7.25 patient months (p= 0.021, relative risk of 7.3). Patients in Group I had one episode of hypertensive encephalopathy per 107 patient months and Group II had one episode per 4.8 patient months (p= 0.001, relative risk of 21.9). On analyzing the outcome, four patients were eventually transplanted, three continued on CPD awaiting a renal transplant, two died and one recovered spontaneously. CONCLUSION: CPD is an effective bridge to renal transplant in children with end stage renal disease. The risk of developing peritonitis and hypertensive encephalopathy varied with the brand of fluid used over time in the same set of patients. PMID- 27408002 TI - Renal and Perinephric Abscesses Revisited. AB - BACKGROUND: This study was carried out to assess the spectrum of renal and perinephric space infection among urology patients admitted in the last three years. METHODS: Medical records of patients with renal and perinephric abscess and emphysematous pyelonephritis were reviewed. RESULTS: Out of 2278 patients admitted in last three years, 29 (1.2%) patients suffered from renal and perinephric space infection, 13 (45%) patients had renal abscess, 11 (38%) perinephric abscess and five (17%) emphysematous pyelonephritis. Sixteen (55%) patients recovered conservatively, nine (31%) patients required percutaneous drainage of the abscesses and remaining four (14%) underwent surgical exploration. The overall mortality was 14% in this study. CONCLUSION: Renal and perinephric space infection continues to be a serious urological problem with high mortality rate. A high index of suspicion, prompt diagnosis, appropriate antibiotics and surgical intervention may be effective in reducing mortality. PMID- 27408003 TI - Effect of Erythromycin on Gastric Emptying Time of Low Birth Weight Babies. AB - BACKGROUND: To study the promotility effects of low dose erythromycin on gastric emptying time in a population of normal low birth weight (LBW) neonates on breast feeds with or without nutritional supplements and human milk fortifier (HMF). METHOD: A randomised control trial involving 50 neonates was undertaken and they were given 6mg/kg/day of oral erythromycin or placebo in three divided doses for four consecutive days in the first two weeks of life. The gastric emptying time (GET) was assessed ultrasonographically by measuring the decrease in the antral cross sectional area (ACSA). The time taken for the ACSA to become half the prefeed value, was taken as t/2 or half GET. The babies were also assessed for pre and post intervention side effects of the drug. The results were analysed using SPSS ver 11.5. RESULTS: The test group showed a significant decrease in GET after the intervention. This effect was mainly seen in the preterm babies as compared to term Small for Gestational Age (SGA) babies. The decrease in GET was more in babies born after 34 weeks of gestation as compared to smaller babies. The reduction in GET was seen in babies on breast milk alone and nutritional supplements with breast milk but not when HMF was added. No side effects of the drug were noted. CONCLUSION: Low dose erythromycin is a safe way of decreasing gastric emptying in preterm babies born after 34 weeks of gestation in the first two weeks of life. PMID- 27408004 TI - Serological Evidence of Chronic Chlamydia pneumoniae Infection in Coronary Artery Disease. AB - BACKGROUND: Recent studies have suggested that Chlamydia pneumoniae infection could be involved in atherosclerosis and related clinical manifestations such as coronary artery disease, carotid artery stenosis and myocardial infarction. METHODS: Serum IgG, IgM and IgA antibodies to chlamydia genus specific antigen were measured by enzyme linked immunosorbent assay (ELISA) in 100 cases of angiographically demonstrated coronary artery disease (CAD) and 100 randomly selected healthy individuals as controls after matching for age and sex. All the samples positive for chlamydia genus specific IgG antibodies were then subjected to Chlamydia pneumoniae species specific IgG antibody ELISA. RESULTS: Seroprevalence of chlamydia genus specific IgG antibodies in control group was 59% with an increase in seropositivity with increasing age. The overall seroprevalence of IgG antibodies was 76% in CAD group and the prevalence was significantly high in all age groups as compared to controls. The odds ratio was 2.20 for seropositivity of chlamydia genus specific IgG antibodies in patients with myocardial infarction (MI) and/or angina than in control group. No significant association was observed for IgA and IgM anti-chlamydial antibodies. The odds ratio for prevalence of Chlamydia pneumoniae species specific IgG antibodies in CAD patients increased to 2.55 in comparison to age and sex matched controls. CONCLUSION: Current study supports the reported association between C pneumoniae infection and CAD in Indian population. PMID- 27408005 TI - Study of Clinicobiochemical Spectrum of Hypothyroidism. AB - BACKGROUND: The aim of this study was to assess the clinico biochemical spectrum of hypothyroidism and the relative importance of thyroid function tests, clinical symptoms and signs in thyroid dysfunction. METHODS: A retrospective study was done and 1702 requisitions for screening of hypothyroidism were analysed. The clinical presentation of cases was correlated with the results of thyroid profile tests. RESULTS: 31.5% of the 1702 cases referred had thyroid dysfunction in the form of subclinical or overt hypothyroidism. In the hypothyroid group generalized weakness, weight gain and myxoedema was common. In cases of primary infertility and depression, subclinical and overt hypothyroidism was high (40% and 45.8% respectively). The average age of females with subclinical hypothyroidism was 30.8 years, 5.4 years less than females with overt hypothyroidism. CONCLUSION: We conclude that hypothyroidism is common and often under-diagnosed. Therefore routine evaluation of female patients with weight gain, generalized weakness, infertility, depression and mood changes should include thyroid profile. PMID- 27408006 TI - Evaluation of Four Elastomeric Interocclusal Recording Materials. AB - BACKGROUND: The fabrication of dental prosthesis requires the transfer of interocclusal records from patient's mouth to semi-adjustable articulators using different kinds of recording media. Any inaccuracy in these interocclusal records leads to occlusal errors in the final prosthesis. This study was conducted to evaluate the dimensional changes occurring in the interocclusal recording material over a given period of time and the material's resistance to compression during the cast mounting on the articulator. METHODS: In this in vitro study, the linear dimensional change and compressive resistance of four commercially available elastomeric interocclusal recording media was tested. Three were addition silicones and the fourth was a polyether material. Cylindrical samples of 10mm diameter of each material were prepared in three different thicknesses of 2, 4 and 6mm. Ten samples each of thickness of 2, 4 and 6mm for all four materials were prepared (total of 120 samples). The linear dimensional changes of the samples were evaluated after 24 hours of fabrication. The compressive resistance was measured when each of these was subjected to a constant compressive load of 25 Newtons. RESULTS: The mean linear dimensional change in a horizontal plane was minimum for Kanibite Hard, an addition silicone. Ramitec showed the maximum linear dimensional change. The mean compression distance was least for Futar D Occlusion (an addition silicone) and maximum for Ramitec (a polyether). It was observed that the samples of thickness 2mm for all the materials underwent least compression. CONCLUSION: The compressive resistance of each elastomer was inversely proportional to the thickness of the sample. This implies that minimum thickness of the recording materials should be used for recording maxillomandibular relations without sacrificing the strength of the interocclusal record. PMID- 27408007 TI - A Study of Efficacy of Misoprostol in Missed Abortion. AB - BACKGROUND: Missed abortion is a common emergency where uterine evacuation is performed by surgical means. METHOD: A total of 30 patients were included in this study to evaluate the efficacy of tablet misoprostol for uterine evacuation in cases of missed abortion. The gestational age ranged from 8-22 weeks. 21 out of 30 patients were primigravidae and the rest multigravidae. Tablet misoprostol (200mcg) was applied vaginally in the posterior fornix every eight hours to a maximum of five tablets. Success rate, complications and side effects were the main outcome measures. RESULTS: The procedure was successful in all cases. Two out of 30 cases required check curettage. Gastrointestinal side effects like vomiting and diarrhoea were seen in few cases. CONCLUSION: The use of tablet misoprostol is effective for uterine evacuation in cases of missed abortion. PMID- 27408008 TI - Immunophenotypic Characterization of Benign and Malignant Prostatic Lesions. AB - BACKGROUND: Biopsy diagnosis is the gold standard for differentiating benign and malignant prostatic enlargements. This study was aimed at supplementing biopsy diagnosis with immunophenotypic characters of prostatic lesions. METHODS: Twenty five cases each of nodular hyperplasia and adenocarcinoma prostate were compared for their morphologic appearances and immunophenotyping, by studying antibodies to prostate specific antigen (PSA), transglutaminase, chromogranin and high molecular weight keratin, proliferating cell nuclear antigen, cell death (apoptosis) and neovascularisation (CD 34). RESULTS: Markers of differentiation (PSA and transglutaminase) aided recognition of higher-grade tumours. PSA negativity avoided metaplasia being overcalled as carcinoma. Loss of basal cells around malignant prostatic acini as determined by high molecular weight keratin (HMWK), was useful in foci of atypical small acinar proliferation and in prostatic intraepithelial neoplasia. Assessment of proliferation indices identified subsets of tumours, within conventional morphologic Gleason's grades, with a higher growth fraction. Cell death determination and study of tumour vessels did not offer any improvement on morphology. CONCLUSION: Immunophenotypic assessment helps in refining morphologic diagnosis of prostatic lesions. Differentiation and proliferation markers objectively assess tumour characteristics with their biologic growth potential and are recommended for diagnostic use. They also help in assessement of response to therapy. PMID- 27408009 TI - Identification of Human Immunodeficiency Virus Type-1 Subtypes by Heteroduplex Mobility Assay. AB - BACKGROUND: Human immunodeficiency virus type-1 (HIV-1) has developed marked genomic sequence differences over the course of an epidemic because of an error prone reverse transcriptase (RT), which rapidly incorporates mutations resulting in genomic diversity, altered cell tropism, immune escape and variable resistance to antiretroviral drugs. The best preventive strategy for HIV control is development of an efficacious prophylactic vaccine using the most appropriate (antigenically related) subtypes. On the basis of phylogenetic analysis, HIV strains can be separated into major group "M" consisting of genetic subtypes A-K, "N", the new group and "O", the outlier group. METHODS: Heteroduplex mobility assay (HMA) is a rapid, economical and reliable technique of subtyping HIV-1. It is based on the principle of determining the genomic relatedness and divergence of the unknown sample with the known reference plasmid HIV-1 subtypes by studying the mobility patterns of the resulting heteroduplexes formed on the polyacrylamide gel. RESULT: A total of 70 HIV-1 seropositive samples obtained from service personnel, their families and civilians from service hospitals were analyzed and their subtype distribution studied. 66 (94.28%) were HIV-1 subtype C and two (2.85%) subtype B. In two (2.85%) samples, the subtype distribution was homotypic recombinant, one each of subtype C1 & C2 and C2 & C4 respectively. CONCLUSION: Service personnel and their families represent a divergent population from different regions of India. An analysis of subtypes in these HIV-1 seropositive individuals will help in understanding the geographical distribution and evolution of the virus. Determination of HIV-1 subtypes has significant implications for development of candidate vaccine for India. PMID- 27408010 TI - Aggressive Use of Diagnostic Services is Counterproductive. AB - BACKGROUND: Medical fraternity requisitions diagnostic tests for multiple reasons. More often than not, the tests lead to more tests either to exclude or to confirm doubts raised by the test results. These tests have an inherent morbidity, discomfort and cost. Growing expenditure on diagnostic tests without matching improvement in the health status warrants an internal audit of the laboratory utilization. METHODS: A retrospective utility audit was done for certain routinely advised laboratory tests at a hospital. Blood urea estimation in annual / periodic medical examination (AME/ PME), bleeding and clotting time in pre-anaesthetic check-up and aspartate aminotransferase (AST) and antibodies to hepatitis C virus (anti-HCV) in diagnostic work-up of acute onset jaundice were included in the audit. RESULTS: During the study period, 793 individuals underwent AME / PME and urea estimation did not provide any additional information in these cases which was not inferred by serum creatinine. Similarly, in diagnostic workup of acute onset jaundice, 6049 aspartate aminotransferase (AST) estimations in 1024 patients did not contribute anything more than what was inferred by alanine aminotransferase (ALT). Prevalence of anti HCV antibodies in acute onset jaundice in serving soldiers (11 out of 1225; 0.89%) though more than that in the blood donors from the same population (17 out of 4105; 0.41%) was less than anticipated false positives (18 out of 1225; 1.5%) as per the claimed specificity (98.5%) of the test kit. None of the 2766 bleeding and clotting time tests detected a bleeding or coagulation disorder. CONCLUSION: The study reveals significant overuse of the laboratory that may not be good for the patient and the organization in terms of direct and indirect costs due to false positive results. This laboratory overload adversely affects the quality and availability of laboratory results. Therefore, a test should only be advised, if positive or negative result would dictate a change in patient management. PMID- 27408011 TI - Verrucous Growth on the Toe. PMID- 27408012 TI - Psychiatric Effects of Traumatic Brain Injury. AB - In India 30,000 people die and 1,25,000 become disabled due traumatic brain injury (TBI). The psychiatric sequalae of TBI can be acute and chronic. Chronic sequalae of TBI are usually ignored and may take the form of defects of cognition, memory, perception, language or intelligence. It may also lead to inappropriate aggression, sexual behaviour, personality change, mood changes, neurosis and psychosis. Neuropsychological assessment of TBI can be pharmacological or behavioural. Survivors of TBI are referred to a walking wounded and require to be cared for. PMID- 27408013 TI - Best Treatment Guidelines For Bronchial Asthma. AB - Asthma is a common disease worldwide with significant ethnic and regional variations. An increasing morbidity and mortality, as well as health care burden from asthma have been recognized lately. Several evidence based guidelines have been developed with an aim to standardize and improve the quality of management. These guidelines seek to translate the advances in the understanding of pathogenesis of asthma and in the development of new agents and strategies into practical application at all levels of healthcare. These advocate an assessment of the patients to classify the severity of diseases followed by a step-wise approach to treatment. With the current management we hope to achieve minimum or nil day time and night time symptoms, prevent acute exacerbations and attain normal or near normal lung function, thus improving the overall quality of life. PMID- 27408014 TI - Management of Respiratory Distress in the Newborn. PMID- 27408015 TI - Single Visit Root Canal Treatment. PMID- 27408016 TI - Neonatal Pharyngeal Perforation. PMID- 27408017 TI - Pneumothorax during Laparoscopic Cholecystectomy. PMID- 27408018 TI - Total Phallic Reconstruction using Radial Artery Free Flap. PMID- 27408019 TI - Bartter's Syndrome Masquerading as a Neurometabolic Disorder. PMID- 27408020 TI - Askin Rosai Tumour. PMID- 27408021 TI - Frostbite of the Pinna and Nose. PMID- 27408022 TI - Amyand's Hernia. PMID- 27408023 TI - Ovarian Sex-cord Tumour with Peutz-Jeghers Polyp and Giant Keratoacanthoma. PMID- 27408024 TI - Orbital Pseudotumour. PMID- 27408025 TI - Pigmented Villonodular Synovitis: Dorsum Foot. PMID- 27408026 TI - Acrorenal Mandibular Syndrome. PMID- 27408027 TI - Lymphoedema Vulva. PMID- 27408028 TI - Pneumosinus Dilatans. PMID- 27408029 TI - A Case of Von Hippel Lindau Disease. PMID- 27408030 TI - Unsual Complication of Ventriculoperitoneal Shunts: Anal Extrusion. PMID- 27408031 TI - Unsual Complication of Ventriculoperitoneal Shunts: Anal Extrusion: Reply. PMID- 27408032 TI - Toxic Epidermal Necrolysis: Reply. PMID- 27408033 TI - Toxic Epidermal Necrolysis. PMID- 27408034 TI - ICU Visitors - Is it Time for a Change in Visitation Policy? PMID- 27408035 TI - Duplicate Publications : A Wake Up Call. PMID- 27408036 TI - Hepatitis B Virus Infection: Emerging Challenges for the Armed Forces. PMID- 27408037 TI - Reduction in Drug Prescription using Biofeedback Relaxation in Neurotic and Psychosomatic Disorders. AB - BACKGROUND: There is a paucity of Indian studies on effectiveness of biofeedback in reducing drug prescription in neurotic and stress related disorders. METHODS: Study sample of generalized anxiety disorders (GAD), mixed anxiety depression, obssessive compulsive disorder (OCD), dissociative disorder and headache were assigned to three groups of 28, 23 and 27 patients respectively. Group 1 were subjected to drug therapy, Group 2 to biofeedback and Group 3 to drugs and biofeedback for 12 weeks. All were followed up at six months and one year. RESULT: At the end of one year, in Group 1, 60.71 % had mild and 17.86 % had moderate anxiety levels, while 21.43% required no further follow up. In Group 2, 39.13 % showed mild and 43.48 % had moderate anxiety levels, while 17.39 % required no follow up. In Group 3, 22.22% had mild and 11.13% had moderate levels of anxiety, while 66.66% required no further treatment. CONCLUSIONS: Biofeedback relaxation with pharmacotherapy is useful in select group of neurotic and psychosomatic cases. PMID- 27408038 TI - Hepatitis B e Antigen Negative Chronic Hepatitis in Indian Patients : A Reality. AB - BACKGROUND: Hepatitis B e antigen negative chronic hepatitis (e(-) CHB) with detectable levels of hepatitis B virus DNA (HBV DNA) in serum has been reported in cases from Asia. This study was undertaken to find out prevalence e(-)CHB and to correlate its presence with the clinical status and severity of the illness in cases of chronic liver disease in India. METHODS: All patients of infective hepatitis, who were hepatitis B surface antigen (HBsAg) positive by enzyme-linked immunosorbent assay (ELISA), were evaluated with liver function tests and HBeAg and antiHBe antibody studies. Polymerase chain reaction (PCR) test was carried out to detect HBV DNA qualitatively. RESULT: Out of 2064 samples tested by ELISA, 429 (20.78 %) were HBsAg positive. HBV DNA (qualitative) was performed on all 429 patients and 74 (17.2%) were HBV DNA positive. Of these only 42 (56.75 %) tested positive for HBeAg. Overall, 8.3 % of HBeAg negative patients (32/384) were viraemic with evidence of chronic liver disease/clinical cirrhosis and alteration of transaminase levels, while three cases (0.84 %) HBeAg positive cases did not show presence of HBV DNA. CONCLUSION: This study shows e(-)CHB prevalence rate of 8.3% in patients with HBV infection in India. Since HBeAg negative patients had detectable levels of HBV DNA as seen in HBeAg positive patients, benefit of antiviral therapy should be given to them. Population studies on e(-) CHB cases are needed to determine its true prevalence, natural course and response to therapy. PMID- 27408039 TI - Epidemiological Investigation of an Outbreak of Enteric Fever. AB - BACKGROUND: Ninety five cases of enteric fever among military recruits from a regimental training centre at Maharastra were admitted to the local military hospital in a few weeks time. METHODS: A descriptive epidemiological study and detailed site survey was undertaken. Blood culture, antibiotic sensitivity test (ABST) with serotyping and phage typing of the isolates were done. RESULT: A total of 95 cases occurred from 31 March 2003 to 17 May 2003. Blood culture for Salmonella enterica serovar Typhi was positive in 60 (63.16%) cases. All the isolates showed same serotype - 9, 12: d: Vi and all belonged to phage type E1 biotype 1 indicating single source outbreak. There was one fatality. There was clustering in time and place indicating a common source outbreak. Exploration of water pipeline supply revealed sewage contamination due to pipeline passing close to a overflowing manhole. ABST revealed multi-drug resistance. CONCLUSION: The outbreak of enteric fever occurred due to sewage contamination of drinking water pipeline. PMID- 27408040 TI - ABC and VED Analysis in Medical Stores Inventory Control. AB - BACKGROUND: The basic principle of inventory control is ABC based on cost criteria and VED on criticality. METHODS: Based on ABC-VED matrix, economic analysis of drug expenditure of priced vocabulary of medical stores (PVMS) section 01 for the year 2003 of a 190 bedded service hospital was under taken. RESULT: Out of 493 drugs in PVMS section 01, only 325 drugs were being used in the reference hospital. The total cost of drugs used was Rupees 55,23,503. Of these 325 drugs, 47(14.4%) drugs were Category A, consuming 70% of total expenditure, 73 (22.46 %) drugs Category B consuming 20% and rest 205 drugs (63.7 %) Category C drugs cost only 10% of expenditure. VED categorization done by consensus opinion of medical officers, found 24 (7.3%) drugs vital, 160 (49.3%) essential and rest 141 (43.3 %) desirable. CONCLUSION: On coupling the two techniques ABC-VED matrix was made and drugs were classified in to Category I (AV+BV+CV+AE+AD) comprising 68 drugs, Category II (BE + CE +BD) 159 and Category III (CD) 98 drugs. The management of Category I drugs was monitored by top management resulting in better control on the annual expenses and at the same time making available the vital Category II by middle and Category III at lower mangerial level. PMID- 27408041 TI - Dental Health Requirements for Psychiatric Patients. AB - BACKGROUND: This study was conducted to assess the dental treatment requirements of psychiatric patients in comparison with the non psychiatric patients admitted in the hospital. METHODS: A total of 103 hospitalised psychiatric patients were examined with an equal number of non psychiatric hospitalized patients. RESULT: 73.22 % of psychiatric patients exhibited higher caries index along with higher decayed missing filled teeth (DMFT) as compared to 68.31 % in the control group. The incidence of periodontal diseases were significantly higher among the study group than the controls. There were statistically significant correlation between smoking, family pattern, calculus index and gingival index amongst psychiatric patients. CONCLUSION: There was a higher incidence of caries index, missing teeth and less filled teeth among psychiatric patients, indicating extensive dental treatment requirement for this group. PMID- 27408042 TI - Evaluation of Bioresorbable vis-a-vis Titanium Plates and Screws for Craniofacial Fractures and Osteotomies. AB - BACKGROUND: Rigid internal fixation with metals is a reliable method of achieving osteosynthesis while allowing the patient passive or even functional loading of the fracture or osteotomised bone segments. The disadvantages with metals have led to the introduction of resorbable polymers in rigid internal fixation. METHODS: This study was conducted to evaluate the efficacy of these polymers as compared to titanium in fixation of bone segments fixation in 40 patients of zygomatic complex fractures and craniosynostosis management. The cases were followed up for one year. RESULT: The stability of the fixation was found to be comparable to metallic fixation though the armamentarium and procedure of fixation of resorbable system was more demanding and the technique sensitive. CONCLUSION: The resorbable system is a good system for rigid internal fixation in specific conditions where muscular and stress forces are not a determining factor in fragment displacement. PMID- 27408043 TI - Impact of Protective Footwear on Floor and Air Contamination of Intensive Care Units. AB - BACKGROUND: Use of protective footwear before entering the intensive care units is enforced with the assumption that it lowers the incidence of bacterial floor colonization. The present study was carried out to find the efficacy of protective footwear on bacterial floor colonization. METHODS: The study was carried out in the intensive care unit of a tertiary care hospital. The study was divided into two phases of two weeks each, phase I with and phase II without use of protective footwear. Samples were taken at six different sites namely footwear exchange area; visitors /staff route; partitioned patient cubicle; central monitoring area; open patient cubicle and scrub up areas. Floor samples were taken at 0600, 1100, 1700 and 2200 hours and air samples at 0600 and 1700 hours. Bacteria were identified and colony forming units (cfu) measured from floor and colony forming units/metre(3) (cfu/m3) from air sample cultures. RESULT: A total of 9521 bacterial colony forming units were isolated from 192 samples in phase I from the floor samples and 9971cfu from 192 samples in phase II. From 96 air samples in each phase, a mean of 262 cfu/m(3) in phase I and 220cfu/m(3) in phase II were isolated. The difference between the two phases was statistically not significant (p value > 0.05 for both). CONCLUSION: Floor and air colony counts showed no significant difference in the two phases with and without protective footwear. Protective footwear had no significant impact on bacterial contamination of floors. PMID- 27408044 TI - Gastric Tonometry as a Prognostic Index of Mortality in Sepsis. AB - BACKGROUND: Splanchnic hypoperfusion in sepsis leads to translocation of bacteria from gut and development of multi-organ dysfunction syndrome (MODS), with increased mortality in critically ill patients. Gastric tonometry can detect this hypoperfusion by measuring carbon dioxide tension (PgCO2) and intramucosal pH (pHi) from gastric mucosa. Therapeutic intervention aimed at improving gut perfusion can improve the outcome and prognosticate the mortality in sepsis patients. METHODS: 100 patients with clinical diagnosis of sepsis were included and divided into two groups of 50 each. Group A patients were managed traditionally without gastric tonometry and in Group B gastric tonometry was used for therapeutic intervention. The intramucosal PCO2, pHi, end tidal carbon dioxide tension (EtCO2) and (PgCO2-EtCO2) differences were monitored at 0, 12 and 24 hours interval. RESULT: Overall mortality in Group A was 64 % and 54 % in Group B. In Group B 45% patients developed MODS and 54 % died with low pHi. As an index of mortality low pHi had a sensitivity of 70% and specificity of 65%. CONCLUSION: There is a good correlation between mortality prediction on the basis of pHi and PgCO2-EtCO2 difference and actual mortality in critically ill patients. The gastric tonometer should be used to predict mortality and guide resuscitation in septicemia. PMID- 27408045 TI - Ocular Surface Changes in Primary Open Angle Glaucoma with Long Term Topical Anti Glaucoma Medication. AB - BACKGROUND: Topical life long anti glaucoma medication forms the mainstay of treatment of primary open angle glaucoma. Their long term usage can cause changes in conjunctival epithelium. METHODS: Hundred cases of primary open angle glaucoma were divided into four groups of 25 patients each. Each group was put on Timolol, Pilocarpine, Brimonidine and Latanoprost respectively. Ocular surface changes were monitored using Schirmer's test, tear film break up time (BUT) and conjunctival impression cytology. RESULT: Altered Schirmer's test value was seen in 40% of patients and reduced tear film BUT values in 26%, at the end of one year. These changes were more in patients treated with timolol. Changes in conjunctival cytology such as decrease in goblet cell density, squamous metaplasia and presence of inflammatory cells were seen in significant number of patients at the end of one year treatment. There was direct relation of duration of treatment to various ocular surface changes. CONCLUSION: Ocular surface changes are seen in significant number of patients of primary open angle glaucoma at the end of one year follow up with topical anti glaucoma therapy. Conjunctival impression cytology is a non invasive technique to monitor these changes. PMID- 27408046 TI - Management of Spontaneous Intracerebral Haemorrhage. AB - BACKGROUND: Management of spontaneous intracerebral haemorrhage (SICH) is still an enigma. The study was conducted to find out the most appropriate mode of treatment and other possible inclusion criteria's in addition to clot size. METHODS: Sixty consecutive patients of SICH excluding bleeds due to arteriovenous malformations/aneurysm were included in the study. Patients with moderate and large bleeds, progressive neurological deficit and glasgow coma scale (GCS) of more than five were included in the surgical group and rest treated conservatively. RESULT: Location of the bleed, other co-morbid conditions and GCS at presentations were more important guidelines than size of the bleed. Mortality was more in surgically treated group where cerebellar bleed fared well after evacuation. CONCLUSION: Surgery is preferred in superficially located bleeds and cerebellar bleeds. Intra cranial pressure monitoring will help in categorizing the mode of treatment better than mere clot size. PMID- 27408047 TI - The Role of anti-HBc IgM in Screening of Blood Donors. AB - BACKGROUND: Transfusion transmitted hepatitis B has always been a dreaded disease, with incidence of increased transmission through donated blood. The screening test for hepatitis B infection is detection of HBsAg that does not rule out the risk of transmission of hepatitis B as the donor may be in the 'window period'. During this period, detection of the antibody to the hepatitis B core antigen (anti-HBc) IgM type serves as a useful serological marker. The aim of this study was to screen blood donors for anti-HBc type IgM and anti - HBc Ag total for detection and to find their incidence amongst blood donors. METHODS: 2552 voluntary blood donors were screened by the ELISA method for HBsAg and anti HBc IgM and other mandatory screening markers. 704 of the test blood samples were also screened for anti-HBc total. RESULT: Of the 2552 donor, 47 (1.84 %) cases were HBsAg positive. A total of 11 (0.43 %) blood units were reactive for HBcAg IgM and of these, 10 (0.39 %) were HBsAg negative and reactive for anti HBcAg IgM. Of the 704 samples tested for anti - HBcAg total, 112 (15.9%) samples were reactive. CONCLUSION: Screening of blood for anti-HBc total is practical in the western world as the incidence of HBsAg and anti-HBc is low in these countries and these positive blood units for anti - HBcAg total can be discarded. This may not be practical in India as the incidence of anti- HBcAg total is high in our population. It is recommended that all blood units should be tested for anti - HBc IgM for infectivity status of the blood donors in the window period and to discard blood if positive. PMID- 27408048 TI - Retrospective Study of Injuries in Military Parachuting. AB - BACKGROUND: This paper analyses the rate and patterns of parachuting injuries at the Sultans Oman Parachute Unit (SOPRA) in Oman. METHODS: Data on 150 patients referred to Rustaq Regional Referral Hospital was collected and analysed. The injuries were defined as severe (fractures, dislocation, head trauma) or minor (contusion, bruises, sprains). RESULT: The rate of severe injuries was 9 % and ankle fractures were the commonest. The minor injury rate was 13.5%. The injury rate increased in relation to age (p < 0.001). The type and possible mechanisms of injury are discussed with the recommendation for reducing the injury rates. CONCLUSION: We conclude that our data compares favourably with other studies except for higher incidence of severe injuries. PMID- 27408049 TI - Exercise in the Management of Coronary Artery Disease. AB - Disability adjusted life years (DALYs) lost can be thought of as "healthy years of life lost". DALYs combine years of potential life lost due to premature death with years of productive life lost due to disability. They indicate the total burden of a disease, as opposed to the resulting deaths. Cardiovascular diseases are responsible for 10% of DALYs lost in low and middle income and 18% in high income countries. The incidence of coronary artery disease (CAD) is increasing in developing countries, partly as a result of increasing longevity, urbanization, and lifestyle changes. CAD burden is projected to rise from 47 million DALYs globally in 1990 to 82 million DALYs in 2020, of which 60% would be from developing countries. DALYs lost per thousand population; age standardized estimates for 2002 for India is 20-29 and is amongst the highest in the world. A report by World Health Organisation (WHO) says that by the end of this century, India would account for more than half of the total heart patients in the world and majority of them would be in the younger age group. This highlights the need for early diagnosis and prevention. PMID- 27408050 TI - Carbon Monoxide Poisoning. PMID- 27408051 TI - Pandemic Response and International Health Regulations. PMID- 27408052 TI - Periochip. PMID- 27408053 TI - Survival After Prolonged Cardiopulmonary Resuscitation. PMID- 27408054 TI - Tubercular Abscess following Intramuscular Injections. PMID- 27408055 TI - Synchronous Gut Duplication Cysts : A Rare Presentation. PMID- 27408056 TI - Glomus Tumour : A Rare Presentation. PMID- 27408057 TI - Intussusception : Pain Abdomen in Paediatrics Revisited. PMID- 27408058 TI - Splenic Infarction in Malaria. PMID- 27408059 TI - Eminectomy for the Management of Closed Lock of Temporomandibular Joint. PMID- 27408060 TI - Aggressive Angiomyxoma. PMID- 27408061 TI - Caroli's Disease. PMID- 27408062 TI - Femoral Neuropathy following Vaginal Hysterectomy. PMID- 27408063 TI - Management of Gastroschisis in a Peripheral Hospital. PMID- 27408064 TI - Fat Embolism Syndrome : A Diagnostic Dilemma. PMID- 27408065 TI - Brain Attack and Stroke Team Concept in Thrombolysis for Acute Ischaemic Stroke. PMID- 27408066 TI - Medical Negligence in Military Hospitals. PMID- 27408067 TI - Medical Negligence in Military Hospitals: Reply. PMID- 27408068 TI - Chronic Kidney Disease : The Looming Threat. PMID- 27408069 TI - Lymphoreticular Involvement in Human Immunodeficiency Virus Infection. AB - BACKGROUND: Although lymphadenopathy, hepatomegaly and splenomegaly are commonly seen in human immunodeficiency virus (HIV) infection, little is known about the prognostic significance of these findings. METHOD: A retrospective study of lymphoreticular involvement in 612 HIV-positive patients was done. RESULT: Lymphadenopathy was found in 301 (49.18%), hepatomegaly in 102 (16.66%) and splenomegaly in 58 (9.47%) patients. Sixty eight (32.54%) of the 209 patients with only lymphadenopathy had acquired immunodeficiency syndrome (AIDS), as compared to 70 (23.97%) of the 292 patients without lymphadenopathy or hepatosplenomegaly (chi(2) 4.49, df-1, p<0.05). There was a higher chance of having AIDS if hepatomegaly was present with lymphadenopathy. Eight (72.73%) of 11 patients with hepatomegaly alone, had AIDS. Thirty (68.18%) of 44 cases with splenomegaly, with lymphadenopathy and hepatomegaly, three (50%) of six cases having splenomegaly with lymphadenopathy and one (33.33%) of three cases with splenomegaly had AIDS. Majority of lymphoreticular involvement cases were due to Mycobacterium tuberculosis infection. All 29 cases with abdominal lymphadenopathy and one with hilar lymphadenopathy had AIDS. Bilateral discrete cervical, axillary and inguinal lymphadenopathy was the most common presentation. CD4 counts were significantly (p<0.05) lower in those with lymphadenopathy and hepatosplenomegaly. CONCLUSION: HIV cases with lymphadenopathy and hepatomegaly should be investigated for the presence of opportunistic infection. PMID- 27408070 TI - Retrospective Analysis of Thyroid Cancer Patients. AB - BACKGROUND: Thyroid cancer is a spectrum of neoplasms and manifests in varied forms. The issues related to presentation, management and outcome of patients with thyroid malignancy are highlighted. METHODS: Retrospective analysis of 70 patients and survival analysis for event free survival was done. RESULT: Papillary carcinomas constituted 88 percent followed by follicular cancers at nine percent of all cancers. Females were affected more than males in the ratio of 2.2: 1. Mean age of presentation for papillary cancer was 39 years and for follicular 50 years. Sixteen percent patients had regional and 10 percent distant metastases. Seventeen percent showed raised serum thyroglobulin and 29 percent had an abnormal whole body scan during the follow up. Relapse rate were similar in those receiving 30 mCi of radioiodine and in those receiving more than 30 mCi. CONCLUSION: The study shows that tumour marker thyroglobulin has higher negative predictive value. Overall prognosis for differentiated thyroid cancers is good. PMID- 27408071 TI - Hormone Receptors, Her-2/Neu and Chromosomal Aberrations in Breast Cancer. AB - BACKGROUND: There is a great deal of disparity in the incidence of breast cancer in rural and urban India on one hand and between India and Western population on the other. METHODS: We analysed steroid receptor status in cases of breast cancer in a small sample of patients in armed forces. Infiltrating duct carcinomas of breast recorded histologically in mastectomy specimens in last two years were accessioned in the present study with reference to patient and tumour characteristics. RESULT: In contrast to the higher rates reported in western literature, only 33 % of the tumours expressed estrogen receptors (ER) and progesterone receptors (PR), of which 24% were ER positive and 30% PR positive. Negative steroid receptor status did not correlate with presence or absence of metastatic nodes, however it was predominant amongst the high grade infiltrating duct carcinomas in this study. Necrosis and lymphovascular invasion demonstrated an inverse relationship with the ER/ PR reactivity. 70% of the node positive cases expressed Her -2/ Neu, reflecting a higher immunoreactivity in this subset of patients. Aneusomy for chromosomes 1, 11 and 17 was common in node positive cases. CONCLUSION: Evaluation of chromosomal aberrations by Fluorescent In Situ Hybridization (FISH) technique correlates well with traditional histological parameters. PMID- 27408072 TI - Immunophenotyping of Tumours. AB - BACKGROUND: Immunophenotyping has added a new dimension to improve the diagnostic accuracy of malignant diseases. The emphasis is on its usefulness in planning and institution of specific therapy besides helping in prognostication. METHODS: The study included 83/1385 biopsies of cancer patients over an 18 month period on which immunohistochemical staining (IHC) with monoclonal antibodies were performed. The technique was used to establish the histogenetic origins/expression of the tumours. The study excluded haematolymphoid malignancies. RESULT: Eighty three cases on whom IHC was performed included poorly differentiated tumours (15), metastatic tumours (16), soft tissue tumours (35), central nervous system tumours (9) and miscellaneous (6). Two cases could not be typed. The clinicopathological correlation in terms of the management and the problems related to its misinterpretation are discussed. CONCLUSION: Immunophenotyping of tumours in an oncology set up is significant in the 'Final Diagnosis'. PMID- 27408073 TI - Prevalence and Determinants of Hypertension in a Rural Community. AB - BACKGROUND: There are few epidemiological studies on prevalence of hypertension and its determinants in rural population. This cross sectional study was done to determine the same in a rural community. METHODS: A random sample of 406 people (218 men and 188 women) of 30 years and above was selected from a rural area. The pre tested proforma was used to collect the data by trained doctors. RESULT: Prevalence of smoking and tobacco use was 16%, alcohol intake 9.4 %, daily salt intake (>= 5 gram) 34.2%, daily saturated fat intake (>= 10 % of daily energy intake) 47 .0 % and physical inactivity (work and leisure) as 18.5%. Body Mass Index (BMI) was >= 25 in 18 % and >= 30 in 3.2% men and women. Prevalence of truncal obesity (Waist Hip Ratio: men >= 0.9; women >= 0.8) was 8.5% with higher incidence in men. Prevalence of abdominal obesity (men >= 102 cms; women >= 88 cms) was found in 15.7 % with higher incidence in men. Differences in prevalence of risk factors between men and women were statistically significant in case of smoking, alcohol consumption and abdominal obesity. 18.5% men and women were suffering from systolic hypertension (>= 140 mg Hg) and 15 % from diastolic hypertension (>= 90 mg Hg). Prevalence of risk factors for hypertension was significantly more among subjects suffering from systolic and diastolic hypertension than normotensive subjects. CONCLUSION: Prevalence of systolic hypertension in rural community was 18.5 % and of diastolic hypertension 15% with higher prevalence in the age group of 60 years and above, in case of men and women. There was a significant linear trend in prevalence of systolic hypertension with respect to age group in men whereas it was not significant in case of women. PMID- 27408074 TI - Seroprevalence of Borrelia burgdorferi in North Eastern India. AB - BACKGROUND: There is paucity of data on Lyme disease in India. A seroprevalence study of B burgdorferi infection was carried out in North-Eastern states of India to assess the same. METHODS: Sera from 500 individuals of North-Eastern states of India were tested for IgG antibody by enzyme linked immunosorbent assay using commercial kits containing recombinant antigen. RESULT: Out of 500 persons, 65 (13%) were positive for B burgdorferi specific lgG Females showed higher positivity rate as compared to males (15.86% vs 10.95%). Higher prevalence rate was observed in the age group of 15-30 years in both sexes (11.48% in male and 18.69% in female). Arunachal Pradesh showed higher seroprevalence rate (17.8%) as compared to other North-Eastern states (8.46-9.6%). CONCLUSION: Seropositivity to B burgdorferi suggests infection by the organism and presence of Lyme disease in these areas. Further population and vector biology studies are required to find out the exact species involved in transmission of the organism. PMID- 27408075 TI - Detection of Bacterial Pathogens in Cerebrospinal Fluid using Restriction Fragment Length Polymorphism. AB - BACKGROUND: Polymerase chain reaction (PCR) is useful for rapid microbial detection in body fluids with low microbial load. It is easier to use universal or broad range primers for the amplification of conserved stretches of DNA common to all bacteria like 16S rRNA gene, followed by restriction fragment length polymorphism (RFLP) of PCR products. METHODS: Forty samples of cerebrospinal fluid were collected. After DNA extraction, universal or broad range PCR was performed using two universal primers U1-5'-CCAGCAGCCGCGGTAATACG-3', corresponding to nucleotides 518 to 537 of the Escherichia coli 16S rRNA gene, and U2 - 5'-ATCGG(C/T)TACCTTGTTACGACTTC-3', corresponding to nucleotides 1513 to 1491 of the same gene. The PCR product was subjected to digestion by endonucleases- HaeIII, Mn11, BstB1 and Alu1. Restriction pattern obtained was compared with that of standard organisms to identify the pathogen. The results were compared with conventional methods. RESULT: Universal PCR could detect pathogens in 20% samples within 13-18 hours as compared to 16% by conventional methods. The analytical sensitivity was 10 Gram negative and 250 Gram positive organisms per 200 MUl sample. Overall sensitivity was 83.3% and specificity was 91.2%. CONCLUSION: Universal PCR followed by RFLP of PCR product is a good alternative to conventional diagnosis of bacterial pathogens. PMID- 27408076 TI - Infectious Disease Markers in Blood Donors. AB - BACKGROUND: The infectious disease markers for which blood donors are screened include anti-human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), rapid plasma reagin (RPR) card test for syphilis and malarial parasites. METHODS: A total of 6751 donors were screened over three years to assess the prevalence of infectious disease markers. Screening for anti-HIV I and II, HBsAg and anti-HCV was carried out by enzyme linked immunosorbent assay (ELISA). Syphilis was tested using RPR card test. Malarial parasite was tested by detection of genus specific plasmodium lactate dehydrogenase. RESULT: The overall seropositivity for anti-HIV I and II was nine (0.13%), for HBsAg 67 (0.99%), for anti-HCV 13 (0.19%) and for syphilis 42 (0.62%). No sample showed malarial parasites. There was no significant difference (p>0.05) in the seropositivity of various markers between voluntary and replacement donors. There was a significant decline (p<0.05) in the prevalence of seropositivity for HCV and syphilis, but not for HIV and HBsAg over the three year period of the study. CONCLUSION: The prevalence of infectious disease markers was similar to that reported by other studies. However, no significant difference was seen in the marker positivity in voluntary and replacement donors, which is at variance from other studies. PMID- 27408077 TI - Vector Databank in the Indian Armed Forces. AB - BACKGROUND: Medical intelligence of disease vectors deals with understanding vector distribution and control. METHODS: An entomological baseline survey using standard vector sampling techniques was done as a pilot study to map the vectors of defence importance in two cantonments of Pune with a view to establish a vector databank and impart training to armed forces personnel in vector surveillance. RESULT: The project trained 142 armed forces personnel in surveillance techniques in three years. Seventeen species of mosquitoes comprising of eight vector species were collected. Three other vectors viz. Rhipicephalus sanguineus, Xenopsylla cheopis and Leptotrombidium deliense are reported. CONCLUSION: The study emphasizes the need for vector mapping /surveillance in each area for preventing morbidity and mortality amongst troops. It also focuses on indigenous fabrication of vector sampling tools and training of personnel for capacity building which in turn will enable such surveys to be undertaken in other units and deployment areas. PMID- 27408078 TI - Medical and Surgical Management of Keratomycosis. AB - BACKGROUND: Fungal keratitis is a diagnostic and therapeutic challenge to the ophthalmologist. If not treated energetically it results in marked ocular morbidity and permanent visual loss. METHODS: Twenty five patients of fungal keratitis were studied for their response to management and final visual outcome. RESULT: Males outnumbered females. Medical treatment was successful in 72% cases, while 28% required surgical intervention. Keratoplasty was done in five patients out of which graft was clear in four after one year of follow up. Three of these underwent optical keratoplasty since therapeutic grafts became opaque. CONCLUSION: Early recognition of the disease and institution of prompt therapy is the key to successful management in fungal keratitis. Occasionally surgical management is required to preserve anatomical integrity of the globe and to salvage useful vision. PMID- 27408079 TI - Admission Cardiotocography Screening of High Risk Obstetric Patients. AB - BACKGROUND: To predict the neonatal outcome in high risk obstetric cases by admission cardiotocography (CTG) testing. METHODS: A total of 150 consecutive high risk obstetric patients meeting the inclusion criteria were subjected to admission CTG testing in this prospective study. The CTG tracing was categorized based on Royal College of Obstetricians and Gynaecologists (RCOG) criteria. Specific foetal and neonatal outcome measures were studied and correlated with the admission CTG testing. RESULT: Foetal distress during labour developed in 15% of patients with a normal test and in 73% of patients with an abnormal test. The admission test had a sensitivity of 66.7%, specificity of 93.3% and a positive predictive value of 53.3% for predicting an Apgar score < 5 at birth. Neonatal admission to neonatal intensive care unit was required in 1% of patients with a normal test and 33% of patients with an abnormal test (p <0.01). CONCLUSION: The result of admission cardiotocography testing could be used to identify patients likely to develop adverse foetal outcomes and help in optimal utilization of labour room resources. PMID- 27408080 TI - Cost-effectiveness Analysis for Technology Acquisition. AB - BACKGROUND: In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology. METHODS: The present study analysed cost-effectiveness of an "In-house" magnetic resonance imaging (MRI) scan facility of a large service hospital against outsourcing possibilities. Cost per unit scan was calculated by operating costing method and break-even volume was calculated. Then life-cycle cost analysis was performed to enable total cost visibility of the MRI scan in both "In-house" and "outsourcing of facility" configuration. Finally, cost-effectiveness analysis was performed to identify the more acceptable decision option. RESULT: Total cost for performing unit MRI scan was found to be Rs 3,875 for scans without contrast and Rs 4,129 with contrast. On life-cycle cost analysis, net present value (NPV) of the "In-house" configuration was found to be Rs-(4,09,06,265) while that of "outsourcing of facility" configuration was Rs-(5,70,23,315). Subsequently, cost effectiveness analysis across eight Figures of Merit showed the "In-house" facility to be the more acceptable option for the system. CONCLUSION: Every decision for acquiring high-end technology must be subjected to life-cycle cost analysis. PMID- 27408081 TI - Prostate Cancer - What's New? AB - Research has shown that prostate specific antigen (PSA) is a tumour marker for diagnosis of cancer prostate with significant prognostic value. Screening studies in North America and Europe have revealed that carcinoma prostate is common. Early detection and treatment improves the quality of life besides preventing deaths due to metastatic prostate cancer. Radical prostatectomy and laparoscopic radical prostatectomy has become the standard treatment for localized prostate cancer in all major uro-oncological centres resulting in reduced mortality. Magnetic resonance imaging and positron emission tomography have helped in detecting local and distant spread of cancer prostate. Revised approach to reduce occurrence of prostate cancer by the use of 5 alpha reductase inhibitors like finasteride and dietary supplements has been instituted. The World Health Organisation (WHO) has recommended lifestyle changes to promote men's health and reduce the incidence of prostate cancer. PMID- 27408082 TI - Plasmodium falciparum Containment Strategy. AB - World Health Organization (WHO) estimates 1.7-2.5 million deaths and 300-500 million cases of malaria each year globally. As an initiative WHO has announced Roll Back Malaria (RBM) programme aimed at 50% reduction in deaths due to malaria by 2010. The RBM strategy recommends combination approach with prevention, care, creating sustainable demand for insecticide treated nets (ITNs) and efficacious antimalarials in order to achieve sustainable malaria control. Malaria control in India has travelled a long way from National Malaria Control Programme launched in 1953 to National Vector Borne Diseases Control Programme in 2003. In India, the malaria eradication concept was based on indoor residual spraying to interrupt transmission and mop up cases by vigilance. This programme was successful in reducing the malaria cases from 75 million in 1953 to 2 million but subsequently resulted in vector and parasite resistance as well as increase in P falciparum from 30-48%. In view of rapidly growing resistance of Plasmodium falciparum to conventional monotherapies and its spread in newer areas, the programme was modified with inclusion of RBM interventions and revision of treatment guidelines for malaria. Early case detection and prompt treatment, selective vector control, promotion of personal protective measures including ITNs and information, education, communication to achieve wider community participation will be the key interventions in the revised programme. PMID- 27408083 TI - Ex-Servicemen Medical Aid Group (ESMAG) : The Hidden Force. AB - Natural calamities such as cyclones, floods and earthquakes are common occurrences in the Indian sub continent which require super human effort to contain damage to men and material. Such events put the dedication, endurance capabilities and organizational skills available in the country to a litmus test. It is not surprising therefore, that the Armed Forces are often asked to spearhead the relief work in such disaster situations. So far, the potential for utilization of disciplined and trained ex-servicemen population for such situations has remained untapped due to the lack of an organizational framework. A concept of tapping this large pool of trained manpower is presented. PMID- 27408084 TI - War Affected Children in Afghanistan. PMID- 27408085 TI - Multidisciplinary Management of Oligodontia. PMID- 27408086 TI - Pseudoxanthoma Elasticum. PMID- 27408087 TI - A Case of Intramedullar Epidermoid Cyst. PMID- 27408088 TI - Ileo-ileal Intussusception Caused by Heterotopic Pancreas. PMID- 27408089 TI - Endoscopic Excision of Recurrent Rhinosporidiosis. PMID- 27408090 TI - Congenital Tuberculosis. PMID- 27408091 TI - Cornual Rupture of Uterus. PMID- 27408092 TI - Secretory Meningioma Mimicking Malignancy. PMID- 27408093 TI - Full Spectrum of VACTERL in New Born. PMID- 27408094 TI - Intraluminal Bronchial Carcinoid Resection by Bronchoscopy. PMID- 27408095 TI - Peripheral T Cell Lymphoma Presenting with Hypereosinophilia. PMID- 27408097 TI - Reply. PMID- 27408096 TI - Scrotal Scintigraphy in a Case of Acute Scrotum. PMID- 27408098 TI - Gastric Tonometry as a Prognostic Index of Mortality in Sepsis. PMID- 27408099 TI - Aggressive Use of Diagnostic Services is Counterproductive. PMID- 27408100 TI - ABC and VED Analysis in Medical Stores Inventory Control. PMID- 27408101 TI - Reply. PMID- 27408102 TI - Reply. PMID- 27408103 TI - The Role of anti-HBc IgM Screening of Blood Donors. PMID- 27408104 TI - Reply. PMID- 27408105 TI - Expanding Armamentarium in Heart Disease. PMID- 27408106 TI - Analysis of Non Enemy Action Deaths in Counter Insurgency Operations through Mortuary Services. AB - BACKGROUND: Regional Trauma Centre in the northern India receives the mortal remains of all fallen soldiers for embalming. Non enemy action deaths during counter insurgency operations (CI Ops) were analysed for planning preventive measures. METHODS: Mortal remains received for embalming from Jan 1999 to Dec 2006 were analysed with respect to mode of injury, causation, body parts involved, fatality, seasonal variation and changing trends. RESULT: Accidents accounted for 3.02 deaths per thousand troops and environmental factors were responsible for 1.14 deaths per thousand troops deployed. Accidental deaths peaked in 2000, declined in 2001 and then remained more or less static. Of the accidental deaths, 88% were brought in dead and 12% died after reaching hospital. Road traffic accidents were the major killers accounting for 48.2%, followed by accidental discharge of weapon 35.5%. The latter is showing a rising trend from 8% of total accidents in 2001 to 65% in 2005 and 51% in 2006 (p<.01). Most (49.7%) of the deaths were below 25 years of age. Proportion of persons below 25 years was more in fatalities due to accidental gunshot wound. Amongst the road traffic accidents, 40% died of head injury and 51.2% due to multiple injuries. When deaths occurred due to accidental discharge of own weapon, 36.4% had brain injury and 22% heart injury. Of the environmental fatalities all but one were brought in dead. Majority were due to avalanches and landslides (51.2%), followed by earthquake (22.4%), lightning (12.8%), high altitude pulmonary oedema (10.4%) and hypothermia (3.2%). Most of the deaths due to avalanches occurred in February while all deaths due to earthquake were in October 2005. Of the deaths due to lightning, 75% occurred in April and May. CONCLUSION: Prevention of death caused by road traffic accidents, accidental discharge of weapon, avalanches and lightning will conserve manpower and add to operational preparedness. PMID- 27408107 TI - Regional Anaesthesia Techniques for Orthopaedic Surgery. AB - BACKGROUND: In recent years, there has been a significant resurgence of interest in regional anaesthesia techniques. Despite various advantages, regional anaesthesia is not used to its full potential in orthopaedic surgeries. METHODS: This study was conducted to evaluate the efficacy and safety of regional anaesthesia techniques in 400 consecutive patients, posted for orthopaedic surgeries in a tertiary care centre. Data was analysed for patient profile, type of surgery, nature of anaesthetic technique used, success rate, complications and satisfaction level of patients. RESULT: Age of patients ranged from three months to 92 years with male preponderance (84.5 %). Regional anaesthesia was used in 85% cases. Most frequently used technique for upper limbs was supraclavicular brachial plexus block (12.05 %) followed by interscalene block (5.58 %) and intravenous regional anaesthesia or Bier's block (2.64 %). For lower limbs, subarachnoid block was used in 50 % cases followed by combined spinal-epidural technique (21.47 %) and paravertebral block (4.70 %). Less commonly used techniques like lumbar plexus block, popliteal fossa block, sciatic + femoral nerve blocks were found to be useful but incidence of partial blocks was high. Overall success rate was 96.17 %. In 22.05 % cases supplementation with analgesic / sedative was needed, whereas in 3.82 % cases, technique was converted into general anaesthesia. There was no major complication. Six patients had reversible sensory neuropathy. In 91.64 % cases, satisfaction level was good to excellent. CONCLUSION: Skilfully performed techniques in regional anaesthesia can facilitate excellent surgical anaesthesia and postoperative pain management. PMID- 27408108 TI - How Robust are our Methods of Detecting Impaired Glomerular Filtration Rate in the Intensive Care Unit? AB - BACKGROUND: Serum creatinine is not a sensitive marker to assess early loss of renal function in acute kidney injury. Timed creatinine clearance and several formula used to predict glomreular filtration rate have not been validated. METHODS: In a prospective observational study in 50 adult patients admitted to the intensive care unit with apparent normal renal function, we assessed the glomerular filtration rate by the formula methods and timed creatinine clearance. RESULT: The mean serum creatinine was 0.77mg/dl, SD +/- 0.15 (range 0.5-1.14 mg/dl). The mean measured creatinine clearance was 87.15 ml/min/1.73m(2), SD +/- 20.5 (range 56.9-137 ml/min/1.73m(2)). In 25 (50%) patients, one hour urinary creatinine clearance was <80 ml/min/1.73m(2) and in two (4%) patients, the creatinine clearance was <60 ml/min/1.73m(2). Spearman correlation coefficient and regression analysis revealed a statistically significant correlation for the Cockcroft-Gault and predictive equations when compared with measured creatinine clearance. The differences between the predictive equations and creatinine clearance, as illustrated by the +/-95% confidence interval in the Bland-Altman graphs was very significant [Cockcroft- Gault = -40.3 to 17.7 ml/min/ 1.73m(2), Modification of Diet in Renal Disease equation = -46.2 to 30.6 ml/min/1.73m(2) and the simplified Modification of Diet in Renal Disease equation = -72.8 to 24.8 ml/min/1.73m(2)]. CONCLUSION: Formula methods and creatinine clearance are more sensitive than serum creatinine in detecting early phase of acute kidney injury. However, there is no agreement between these methods of glomerular filtration rate estimation. PMID- 27408109 TI - Exomphalos Defects : A Review of 15 Cases. AB - BACKGROUND: The outcome after repair of exomphalos defects has improved significantly with refinements in surgical techniques, multidisciplinary management and monitoring of intra-abdominal pressures. METHODS: A retrospective study of medical records of 15 cases with omphalocele was done. RESULTS: Antenatal diagnosis was available in six cases. There were eight females and seven males with a mean birth weight of 2.2 kg. Nine babies had associated anomalies. There were nine major (defect size> 5 cm) and six minor defects. Immediate closure in neonatal period was carried out in 12 cases. Urinary bladder pressure (UBP) was measured to assess intra-abdominal pressure in cases where primary closure was difficult. Primary closure was omitted in the event of intravesical pressures exceeding 20 mm Hg (~ 25 cms of water). Primary surgical closure was possible in five (56%) major cases. Two cases were subjected to silo repair followed by delayed primary closure whereas the other two required a Goretex mesh closure. Three minor defects could be repaired primarily whereas the remaining three were managed conservatively and closed at age of 9 to 12 months. There were no significant anaesthetic complications. Elective postoperative ventilation was required in one baby. There were three deaths at ages five, nine and ten months due to unrelated causes. CONCLUSION: Satisfactory outcome is possible in cases with exomphalos defects with intra-operative intravesical pressure assessment forming a convenient method for excluding abdominal compartment syndrome. PMID- 27408110 TI - Anaesthetic Issues in In-vitro Fertilisation. AB - BACKGROUND: Ultrasonically guided transvaginal oocyte retrieval is a relatively short procedure that is performed on an outpatient basis. Any anaesthetic technique may interfere with certain aspects of human oocyte fertilisation or embryo implantation. The optimal anaesthetic technique should allow good surgical anaesthesia with minimal side effects, a short recovery time and high rate of successful pregnancy. METHOD: We present our experience and evaluation of the various techniques studied to carry out this technique. RESULTS AND CONCLUSION: Amongst the various available total intravenous anaesthesia options, propofol/ remifentanil or fentanyl technique of sedation appears to be safe and effective. PMID- 27408111 TI - Splenic Syndrome due to Sickle Cell Trait amongst Indian Soldiers Serving in Kashmir. AB - BACKGROUND: Heterozygous transmission of gene for Haemoglobin S leads to sickle cell trait. Mostly the trait remains silent with no additional morbidity or mortality. When these persons migrate to higher altitudes, in times of high oxygen demand, some of them develop splenic infarction. This is a rare phenomenon and only 47 such cases had been reported till 2005. METHODS: This study was conducted at an Indian military hospital serving the troops deployed in Kashmir valley at altitudes ranging from 5500 ft to 13000 ft. When two consecutive splenectomies for splenic abscesses, turned out to be sickling induced infarction histopathologically, we reviewed splenectomy specimens received in last six years for evidence of sickling. RESULT: Out of 33 splenectomies performed during the period of study, 22 were due to trauma (gun shot injury 11; splinter injury one and blunt injury 10). Of the rest eleven, who presented without any history of trauma, seven had evidence of vascular occlusion with aggregates of sickled red blood cells. In none, Gram stain or Periodic Acid Schiff stain revealed any bacterial or fungal colonies. One patient of splenic syndrome was found to have unrecognised sickle cell trait and he was managed conservatively. CONCLUSION: Sickle cell trait should be excluded before considering splenectomy in ethnically vulnerable patients presenting with splenic syndrome. An uncomplicated splenic infarction can be managed conservatively. PMID- 27408112 TI - Risk Factors for Suicide in Wives of Military Personnel. AB - BACKGROUND: An increasing trend in attempted and completed suicide amongst wives of serving personnel was observed. METHODS: A questionnaire designed to elicit the known risk-factors for suicide, suicide attempts and suicidal ideation by women in the Indian context was administered to 222 wives of Indian military personnel living in a garrison with their husbands. RESULT: A large number (28%) of the sample were child-less. Alcoholism in husband was reported by 22 women and domestic violence by four. Six had been bereaved in the past year. Chronic illness was reported by 10 women and psychiatric illness by four. CONCLUSION: Wives of military personnel may need targeted community interventions focusing on the risk factors for suicide. PMID- 27408113 TI - Comparative Study of Blood Cross Matching Using Conventional Tube and Gel Method. AB - BACKGROUND: Conventionally tube method is used for compatibility and cross matching in transfusion medicine. METHODS: A comparative study was carried out to evaluate the efficacy of conventional tube and gel technique. RESULT: Compatibility testing was performed on 1000 blood samples by conventional test tube method and DiaMed gel method. The results were analysed. CONCLUSION: The gel method was found to be a rapid and reliable procedure without controls. There was no requirement of wash phase in indirect antiglobulin test and sensitivity and specificity was comparable to spin tube method. We conclude that this technique is a better substitute for spin tube method. PMID- 27408114 TI - Percutaneous Closure of Perimembranous Ventricular Septal Defect with Amplatzer Device. AB - BACKGROUND: The Amplatzer perimembranous ventricular septal occluder is an innovative device for percutaneous closure of perimembranous ventricular septal defects (PMVSD). In appropriately selected cases this procedure is safe and effective. METHODS: Fourteen patients with the mean age 10.53 years (range 18 months to 55 years) and mean body weight 20.64 kg (range 6 to 52 kg) underwent PMVSD closure. RESULT: The PMVSD mean diameter was 5.28 mm (range from 4 to 9 mm). Implantation was successful in 92% of the cases and all patients had complete occlusion of the shunt within three months. CONCLUSION: Device orientation was excellent in all cases. Device-related aortic insufficiency, tricuspid insufficiency or left ventricular dysfunction was not observed. One patient had embolisation of the device and another had complete heart block which required a permanent pacemaker implantation. The excellent short term results need to be confirmed over long-term follow-up. PMID- 27408115 TI - Neuroses among Armed Forces Personnel. AB - BACKGROUND: The phenomenon of "Military Family Syndrome" has been hotly debated. Mental disorders are however, important causes of morbidity in the armed forces. METHODS: A cross sectional study was carried out on 600 randomly selected troops and families in a large military station. General Health Questionnaire 12 (GHQ 12) was used as a screening test for neuroses. Neuroses was defined as score of three and above on the GHQ-12. RESULT: Overall prevalence of neuroses was 31.34% with 95% confidence interval between 27.41% and 35.55%. Gender did not have any effect on prevalence of neuroses nor did marital status. The soldiers in the age group of 25-36 years were most affected. Neuroses was more common in the lower ranks and among troops who belonged to arms. Among wives, age, rank and type of service (whether from arms or services) of husband were not associated with neuroses. CONCLUSION: There is a need for preventive psychological services in the armed forces. Leadership and man-management sensitive to changing needs of the soldier should be promoted. PMID- 27408116 TI - Contraceptive Effectiveness of Levonorgestrel Releasing Intrauterine System. AB - BACKGROUND: This study evaluated the contraceptive effectiveness of progesterone releasing intrauterine contraceptive devices (IUCD) and compared it with the Copper T device. METHODS: Seventy patients were selected in each group. Menstrual charts were maintained and data recorded at one, three, six months and one year after insertion of the device. RESULT: One year follow up was completed by 66 patients in the Levonorgestrel Releasing Intrauterine System (LNG-IUS) group and 62 in the Cu T group. They were age, parity and education level matched. The mean duration of menstrual flow for the LNG-IUS group was 3.6 days and that for CuT group was 5.1 days (p>0.05). Insertion of LNG-IUS was found to be significantly difficult than the Cu T 380, with increased pain at insertion (p<0.05). There was no pregnancy in the LNG-IUS group and expulsion rates were low. The most significant difference was scanty periods and at times amenorrhoea in the LNG-IUS group. Termination rates for various reasons were almost equal in both groups. CONCLUSION: Both devices were effective, safe, well accepted and tolerated. LNG IUS scores high in patients with preexisting menorrhagia or dysmenorrhoea while Cu T 380 has advantages of lower cost, ease of insertion and comparable efficacy. PMID- 27408117 TI - Clinical Profile of Special Children at Asha Centre. AB - BACKGROUND: The care of special children suffering from cerebral palsy, deaf mutism, mental retardation (MR) and post encephalitic sequelae etc. is done in the armed forces at "ASHA" centre supported by Army Wives Welfare Association (AWWA). METHODS: The clinical profile and underlying etiological factors in these children were studied. RESULT: Out of 30 children studied, majority were males. The commonest disability was cerebral palsy, seen in 13 (43%) cases followed by mental retardation in six (20%) and post encephalitic sequlae in four (13%) cases. Convulsions were noticed in 12 (40%) cases. The delayed speech was a significant handicap observed in 27 (90%) cases. CONCLUSION: Among the etiological factors, natal causes and infections are leading factors in these children and there is an urgent need to strengthen the existing maternal and child health services in our country. PMID- 27408118 TI - Magnetic Resonance Urography in Obstructive Uropathy. AB - BACKGROUND: Urinary obstruction is one of the few reversible causes of renal failure. Early diagnosis and treatment can salvage the kidney. Presently intravenous urography, ultrasonography, computed tomography and magnetic resonance imaging are in vogue to detect the cause and demonstrate the site of obstruction. METHODS: An evaluation of imaging technique in obstructive uropathy was undertaken in a group of 25 patients. RESULT AND CONCLUSION: Magnetic resonance urography delivered highest accuracy amongst the techniques studied. PMID- 27408119 TI - Acute Mountain Sickness, High Altitude Cerebral Oedema, High Altitude Pulmonary Oedema: The Current Concepts. PMID- 27408120 TI - Coronary Artery Revascularisation : Past, Present and Future. AB - The high prevalence of coronary artery disease has inspired the development of technologies and techniques for coronary revascularisation, including coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). PCI have witnessed the impact of innovation with newer hardware and drug eluting stents (DES). DES have indisputably reduced restenosis, however there is an emerging concern over the risk of late stent thrombosis associated with their use. We discuss the limitations of the current generation DES and review advances in the stent technology. The technology used in CABG has improved, resulting in off-pump coronary artery bypass (OPCAB), endoscopic, video-assisted, and robot assisted CABG with automated one-shot distal anastomotic devices being used increasingly. The difference in adverse outcomes between CABG and PCI continues to decline and the future may witness a close collaboration between the two. PMID- 27408121 TI - Transcranial Magnetic Stimulation : A New Therapeutic Tool in Psychiatry. PMID- 27408122 TI - Dengue Vaccine: The Current Status. AB - Dengue fever is a re-emerging public health problem with two-fifths of the world population being at risk of infection. Since there are no antiviral drugs available against the dengue virus, and vector control programmes have been largely unsuccessful in preventing outbreaks, vaccination seems to be the most viable option for preventing infection. An ideal dengue vaccine should provide long lasting immunity against all four serotypes of the virus. The envelope protein of the virus plays a key role in vaccine development. The present day candidate vaccines includes a live attenuated tetravalent vaccine, intertypic chimaeric vaccines based on live attenuated dengue virus vectors, chimaeric vaccines based on the live attenuated Yellow Fever 17D vector and recombinant vaccines which include vaccines based on flavivirus and non-flavivirus vectors. Tetravalent live attenuated vaccines, intertypic chimaeric vaccines and chimaeric vaccines are being tested in human trials. Recombinant DNA vaccines based on flavivirus and non-flavivirus vectors are being tested in animal trials. Recent studies have shown that the tetravalent formulations may elicit an unbalanced immune response. Research is continuing to find means of obtaining a balanced response to all antigens in the tetravalent formulations. PMID- 27408123 TI - Blood Bank on Wheels : A Novel Concept. AB - The concept of supplying safe and screened blood to casualties in war has been a problem over the years. Using the equipments available in a Corp Blood Supply Unit, we describe a simple modification of a vehicle for blood supply and its potential use as a mobile blood bank. PMID- 27408124 TI - Atovaquone/Proguanil : A New Drug Combination to Combat Malaria. PMID- 27408125 TI - Drug Induced Obsessive Compulsive Disorder in Schizophrenia. PMID- 27408126 TI - Gastric Stromal Tumour presenting as Upper Gastrointestinal Bleed. PMID- 27408127 TI - Supernumerary Tooth in the Nasal Cavity. PMID- 27408128 TI - Management of Gastroschisis in a Remote Hospital. PMID- 27408129 TI - Acute Bilateral Hypopyon in Acute Lymphocytic Leukaemia. PMID- 27408130 TI - Acute Myeloid Leukaemia : AML M0 with 11q deletion. PMID- 27408131 TI - Symmetrical Peripheral Gangrene complicating Staphylococcal Toxic Shock Syndrome. PMID- 27408132 TI - Cervical Pregnancy : An Uncommon Ectopic Pregnancy. PMID- 27408133 TI - Congenital Malaria. PMID- 27408134 TI - Port Site Hernia : A Rare Complication of Laparoscopy. PMID- 27408135 TI - Hiatus Hernia in a Ten Year Old Boy. PMID- 27408136 TI - Pouch and Tunnel Technique for Root Coverage using Palatal Connective Tissue Graft. PMID- 27408137 TI - Adnexal Torsion in Second Trimester of Pregnancy. PMID- 27408138 TI - Dual Transcatheter Intervention in Ventricular Septal Defect and Pulmonary Valvular Stenosis. PMID- 27408139 TI - Surgical Management of Aortic Stenosis in a Child. PMID- 27408140 TI - Medical Negligence in Military Hospitals. PMID- 27408141 TI - Medical Negligence in Military Hospitals: REPLY. PMID- 27408142 TI - Ex-servicemen and Serving Personnel are Consumers at Military Hospitals! PMID- 27408143 TI - Ex-servicemen and Serving Personnel are Consumers at Military Hospitals!: REPLY. PMID- 27408144 TI - Walking into Sunset. PMID- 27408145 TI - Anaesthesia for Paediatric Cardiac MRI. AB - BACKGROUND: General anaesthesia (GA) for cardiac magnetic resonance imaging (MRI) in patients with congenital heart disease (CHD) is challenging for the anaesthesiologist. METHODS: A retrospective review of anaesthesia for cardiac MRI between January 2002 and December 2005 was undertaken. RESULT: 28 children with cardiac disease were subjected to general anaesthesia for cardiac MRI, of which four patients were in ASA Grade I, five in Grade II, seventeen in Grade III and two in Grade IV. Two patients had undergone previous cardiac surgery. All the cases were managed as inpatients, of which 18 had cyanotic cardiac defects (SpO2 between 65 and 85%). On two occasions scans were interrupted because of low oxygen saturation or haemodynamic instability during GA. No patient was admitted to the hospital for complications related to general anaesthesia though all were kept under observation for two hours before being shifted to ward. Five patients had a brief episode of hypotension/desaturation during the MRI and responded quickly to interventions. CONCLUSION: General anaesthesia for cardiac MRI can be administered safely in children with CHD. PMID- 27408146 TI - Primary Plating of Displaced Mid-shaft Clavicular Fractures. AB - BACKGROUND: Recent studies have shown that displaced mid-shaft clavicular fractures do not have assured favourable outcomes with non-operative management and nonunion rates could be as high as 20%. In addition many malunite with significant shortening. Non-union or malunion causes functional deficit and many of them may benefit from primary internal fixation. METHODS: We reviewed the results of twenty cases of displaced/comminuted midclavicular fractures, which were treated with primary open reduction and internal fixation with a reconstruction plate placed over the superior surface of clavicle. RESULT: All the fractures clinically united by eight weeks. As per Rowe criterion 12 had excellent, six good and two fair results. On an average patients had full functional recovery in four months. CONCLUSION: Primary internal fixation of displaced comminuted mid-shaft clavicular fractures leads to predictable and early return to function thus preventing unacceptably high complication rates of nonoperative management of these fractures. PMID- 27408147 TI - Daily Fetal Movement Count Chart : Reducing Perinatal Mortality in Low Risk Pregnancy. AB - BACKGROUND: A reduction or cessation of fetal movements (FMs) is frequently reported by pregnant women resulting in anxiety and concern. Formal counting of FMs by the pregnant woman could possibly identify the fetuses at risk. METHODS: A prospective study was carried out over 500 booked cases after introducing daily fetal movement count (DFMC) Chart in the ninth month of pregnancy. Prior ultrasound (USG) was done in all cases. DFMC chart was used to record number of fetal movements perceived by patient for one hour after food (breakfast, lunch, dinner). Fetal movements were considered satisfactory if the count was three or more on each occasion. RESULT: During the study period, no fetus was lost after introduction of DFMC chart in the 250 cases that were given DFMC chart and delivered in our hospital (Nil perinatal mortality). This was compared with 250 booked cases that were not given DFMC chart but had normal ultrasound done after completion of eight months of pregnancy and followed up. Five intrauterine deaths occurred in the ninth month in control group (2% perinatal mortality). In the DFMC chart group, 15 patients were admitted with decreased fetal movements. Out of these, 12 were discharged after monitoring for three days and three cases were delivered. CONCLUSION: DFMC chart in ninth month of pregnancy helps in identifying at risk fetus in low risk pregnancies in absence of any other adverse factors necessitating early delivery. PMID- 27408148 TI - Impact of Nasal Symptoms on the Quality of Life of Fresh Inductees in High Altitude. AB - BACKGROUND: Troops deployed in high altitude areas of Ladakh face nasal problems in the form of obstructive nasal symptoms and recurrent epistaxis. This study analyses the changes in the nasal mucociliary transit times (NMTT) and deterioration in quality of life of troops on first high altitude induction. METHODS: A prospective study on 100 healthy volunteers was done. Mucociliary transit time was measured and a standardized quality of life questionnaire (RQLQ) administered at onset and after a period of three months in high altitude. Thereafter the subjects were divided into two groups and the study group was administered normal saline nasal drops. The observations were taken and results were statistically analysed after a period of three months. RESULT: The mucociliary transit time was prolonged after a three month stay in high altitude (p< 0.005). Normal saline nasal drops were successful in improving the nasal mucociliary transit times (p < 0.05). There was a statistically significant derangement in the quality of life which was improved by administering normal saline nasal drops (p<0.05). CONCLUSION: An increased muco-cilliary transport time after exposure to high altitude denotes a deranged physiology of the nasal mucosa. This leads to a statistically significant adverse impact on the quality of life of the troops deployed. The use of normal saline nasal drops is a simple and effective method of reversing some of these changes. PMID- 27408149 TI - Management of Mandibular Fractures. AB - BACKGROUND: To evaluate the cases of mandibular fractures treated by open reduction and rigid fixation at the Armed Forces Medical College, Pune. METHODS: Two hundred and thirteen mandibular fractures cases were treated by open reduction and rigid fixation from Jun 1998 to Jun 2006. These were retrospectively analyzed based on the following patient related factors i.e. mode of injury, age and sex distribution, site of injury, associated injuries and surgical treatment. RESULT: The significant finding was that the most common etiology for fracture mandible was road traffic accidents (RTA), [196 (92%)]. Of the patients who reported, 147 (95.4%) were males in the third decade of life. 96 (45%) patients had parasymphysis fractures, 65 (30.5%) had angle fractures, 33 (15%) subcondylar fractures, 17 (7.9%) body fractures and 2(0.9%) had ramus fracture. Early intervention using open reduction and internal fixation was the protocol followed which resulted in minimum morbidity and complications. CONCLUSION: As RTA especially two wheelers accidents appeared to be the most common cause of mandibular fractures, use of suitably designed protective head gear (crash helmets) is advisable. Moreover open reduction and rigid internal fixation appears to be the suitable treatment modality in successful treatment of mandibular fractures in reducing morbidity and complications and ensuring early return to normalcy. PMID- 27408150 TI - Gender Inequality: Is the National Population Policy's Objective of Two Child Norm Heading the Correct Way? AB - BACKGROUND: Male Preference is well known phenomena world wide from ancient ages. A descriptive study was carried out to assess the attitude of women towards birth of son, use of contraception methods and sex determination methods in rural village Kasurdi in Pune district. METHODS: Univariate analysis was carried out by considering each factor determining sex preference separately as well as using a Logistic Regression Model. Adequacy of fit of the model has also been tested. RESULT AND CONCLUSION: Out of 110 respondents interviewed, 62.7% felt that male child is necessary in the family. Univariate analysis revealed that sex of first child, concern undergone for second pregnancy with regards to sex of the child, number of children in family and type of family were significant factors contributing to the son preference. The analysis under the logistic regression model revealed that sex of the first child and concern undergone in second pregnancy with respect to the sex of the second child are the most dominating and significant factors in the causation of son preference. The difference between family sizes when compared with the sex of first child was statistically significant signifying that if the first child is a male then it hardly matters whether the second child is male or female, but if the sex of first child is female then the families land up with bigger family size. On an average most of the respondents favour two children with an equal share of male and female children. PMID- 27408151 TI - Outcome of Alcohol Dependence Syndrome Cases Managed in Armed Forces. AB - BACKGROUND: Army Order for Alcohol Dependence Syndrome gives a structured and strict approach towards disposal of such cases in Indian Armed Forces. Four years have passed since the implementation of the above order. This study was conducted to assess the outcome after implementation of the said order. METHODS: 231 male soldiers reporting for review after six months and one year of initial treatment were included in the study. Data was obtained from history, physical examination, mental state, laboratory and other investigations. The data was analyzed and compared with previous study. RESULT: 231 patients were reviewed in this period of four years, of which 149 patients were reviewed after six months and 77 after one year. Five patients were reviewed beyond one year. 50 - 53% patients have shown complete improvement after the initial treatment and 23.5 - 31% have shown partial improvement after the initial treatment. The rest did not show much improvement. The results are better than the previous results from study conducted before implementation of the new Army Order. CONCLUSION: The study strengthens the validity of the present Army Order, which is structured and may be having a deterrent value, leading to better prognosis. PMID- 27408152 TI - Determinants of Nutritional Status of School Children. AB - BACKGROUND: A cross sectional study was carried out to determine the nutritional status of school children in Army School, Pune. METHODS: Anthropometric survey of 760 school children was carried out and compared against the NCHS/WHO reference standards to determine their nutritional status. Associations of nutritional status with socio-economic status, education status of parents, mothers working status and family size were determined. RESULT: The prevalence of stunting was 13.81%, wasting 6.71% and under nutrition 9.87%. Mothers' educational level, wasting, socio economic status and family size were significantly associated with the nutritional status of the child. CONCLUSION: Maternal educational status, socio-economic status and family size are important determinants of nutritional status of school children. PMID- 27408153 TI - Lithoclast((r)) Master in Intracorporeal Lithotripsy during Percutaneous Nephrolithotomy : Our Experience. AB - BACKGROUND: This study was carried out to compare the efficacy of Lithoclast((r)) Master with pneumolithotriptor during percutaneous nephrolithotomy (PNL) in the treatment of renal staghorn calculi. METHODS: In this prospective study, 60 patients suffering from partial or complete staghorn renal stones were included. Patients were divided randomly in two groups : Groups I and II and underwent PNL for removal of stones. In Group I patients, standard pneumolithotriptor and in Group II, Lithoclast((r)) Master was used for stone fragmentation. The patients were evaluated for rate of fragmentation/clearance, presence of residual fragments by KUB radiograph/ultrasound. Result was analyzed by Chi-square test. RESULT: The rate of fragmentation using Swiss Lithoclast((r)) Master was more effective and quicker in comparison to standard pneumolithotriptor. The average time taken for fragmentation and clearance in Group I using pneumolithotriptor was 65 minutes, whereas it was 58 minutes using Lithoclast(r) Master, which was statistically significant (p< 0.01). Only 4% patients had significant residual fragments (> 4mm) in Group II and 16 (53%) patients in Group I, which was significant (p < 0.01). The complications in both the modalities were insignificant; one (1.33%) patient had bleeding and three (10%) patients had urine leak in Group I; whereas three(10%) patients had bleeding and five (16.7%) urine leak in Group II. CONCLUSION: Lithoclast((r)) Master is an effective intracorporeal lithotripter during percutaneous nephrolithotomy in the treatment of renal staghorn calculi for stone fragmentation/clearance with minimal residual fragments and complications. PMID- 27408154 TI - Role of Ultrasound Therapy in the Healing of Tibial Stress Fractures. AB - BACKGROUND: Stress fracture is the single most common cause for the lost number of manpower days during training. The conventional treatment options begin with rest and cessation of precipitating activity. However the demands of military training provide little tolerance for prolonged periods of rest. In the recent past ultrasound therapy (UST) has been reported to speed up healing of stress fractures. METHODS: In the present study, a total of 67 cases of stress fracture were studied for the effect of ultrasound therapy on healing time. Study protocol used was double blind placebo controlled. RESULT: Study results showed that the mean number of days of incapacitation was 25.46 days in the ultrasound treatment group as compared to 39.92 in the placebo group, a difference of 14 days, which was statistically highly significant. CONCLUSION: The results of the study convincingly prove that ultrasound treatment is effective in cases of stress fracture. PMID- 27408155 TI - Nuchal Cord : A Retrospective Analysis. AB - BACKGROUND: The nuchal cord is often blamed for problems that are encountered during delivery and is often cited as a major cause of fetal distress and perinatal mortality. However, the actual significance of nuchal cord on the outcome of an infant is controversial. A retrospective study was done to investigate the actual frequency of nuchal cords encountered in a hospital setting and to determine its effect on an infant as it passes through the birth canal and immediately after delivery. METHODS: A retrospective study was carried out in 350 deliveries (out of total 367 deliveries) including 65 cases of nuchal cord from July to December 2005. Nuchal cord group was divided into loose nuchal cord (cord could easily be uncoiled before delivery of the newborn) group and tight nuchal cord (cord was needed to be clamped and cut before delivery) group. The mode of delivery, complications and fetal outcome of nuchal cord groups was compared with rest of the deliveries. Seventeen cases (including three cases of nuchal cord) having complications as intrauterine growth retardation, oligohydramnios (AFI <5), antepartum haemorrhage, severe pregnancy induced hypertension and maternal medical complications were excluded. RESULT: We found that the loose nuchal cord group did not have any significant difference in mode of delivery or fetal outcome as compared to control group however the group having tight cord around the neck had significantly higher proportion of fetal distress and low Apgar scores at one minute. CONCLUSION: Loose nuchal cord doesn't increase the chances of cesarean delivery whereas tight cord around the neck may result in lower Apgar scores at one minute and increased incidence of fetal distress. PMID- 27408156 TI - Epidemiological Investigation of a Typhoid Outbreak. AB - BACKGROUND: An outbreak of typhoid fever among school children of a school in military station in central India is reported here. It comprises of 98 students out of which 87 students were from one school. METHODS: Detailed epidemiological case sheets were filled for cases and active case finding surveys were conducted among the school students during the period of study. It included 3313 students of the affected school. RESULT: Attack rate of the affected school was 2.62 percent (RR 13.38, 99% CI of RR 10.8, 16.12). Blood samples were found to have Salmonella typhi in 5.43%. Eighty six blood samples (87.75%) were positive for Widal test. Sanitary survey revealed fecal contamination of water supply leading to the outbreak. CONCLUSION: We recommend having a sound vaccination programme for children, adequate chlorination of water supply and formation of local groups at school level to monitor water quality on a daily basis. PMID- 27408157 TI - Male Andropause : A Myth or Reality. AB - Male andropause, male climacteric or viropause is a condition in which men suffer from complex symptomatology due to low androgen level with aging. After the age of 40 years testosterone level starts declining and andropause corresponds to the age at which a pathogenic threshold is reached. This review summarizes the etiology, consequences, screening, diagnosis, monitoring of androgen deficiency in aging male (ADAM). The pros and cons of testosterone replacement therapy (TRT) in elderly male have been discussed. Currently oral, transdermal, transbuccal, intramuscular, and subcutaneous implants are available for clinical use. The choice is made by physicians based on therapeutic indication and patient preferences. PMID- 27408158 TI - Post-exposure Prophylaxis : What Every Health Care Worker Should Know. PMID- 27408159 TI - Therapy for Cessation of Smoking. AB - Tobacco dependence is a chronic relapsing medical illness. Unfortunately more than 1.1 billion people worldwide smoke tobacco. Tobacco consumption rate is very high in India. Providing three minutes counseling by physicians doubles the cessation rate as compared to no intervention. Nicotine replacement products (gums, transdermal patch, nasal spray, inhaler and lozenge), bupropion and varenicline used with counseling by physicians double the cessation rates at one year. There are drugs like buspirone, naltrexone, mecamylamine and silver acetate; some of which either alone or in combination with any of the above drugs may be routinely used in near future for smoking cessation in at least some specific groups of population. The most difficult problem for patients in smoking cessation is withdrawal symptoms. Counseling with continuous support from physician, family members, friends and overall from the society will help in achieving a higher rate of smoking cessation, with the final aim of making ours a tobacco smoke-free world for future generations. PMID- 27408160 TI - Automated Target Controlled Infusion Systems : The Future of Total Intravenous Anaesthesia. PMID- 27408161 TI - Multivitamins : Use or Misuse? PMID- 27408162 TI - Congenital Cystic Adenomatoid Malformation of Lung. PMID- 27408163 TI - Lobular Capillary Hemangioma of Nasal Cavity. PMID- 27408164 TI - Toxic Epidermal Necrolysis Managed with Immunoglobulin. PMID- 27408165 TI - Lower Gastrointestinal Vascular Malformation in Children. PMID- 27408166 TI - Antenatal Diagnosis of Omphalocele. PMID- 27408167 TI - A Case of Dual Intussusception. PMID- 27408168 TI - REAH : Unusual Case of Unilateral Nasal Blockage. PMID- 27408169 TI - Retrograde Jejunogastric Intussusception with Strangulation after Posterior Gastrojejunostomy. PMID- 27408170 TI - Obturator Hernia : An Elusive Diagnosis. PMID- 27408171 TI - Hereditary Factor X (Stuart-Prower Factor) Deficiency. PMID- 27408172 TI - Case of Dual Chamber Pacemaker with Cross Stimulation. PMID- 27408173 TI - Large Epiphrenic Diverticulum of Esophagus. PMID- 27408174 TI - Ocular Injuries from Plant Sap in Army Soldiers. PMID- 27408175 TI - Congenital Unilateral Bowing of Tibia and Fibula. PMID- 27408176 TI - Tuberculosis of Cervix. PMID- 27408177 TI - A Case of Depression with Narcolepsy. PMID- 27408178 TI - Tear Break-up Time in High Altitude Areas. AB - BACKGROUND: In high altitude areas, patients report with irritation, redness and foreign body sensation in their eyes suggesting tear film abnormality due to low humidity and windy environmental conditions. METHODS: Tear Break- up Time (TBUT) was studied in 100 subjects consisting of local population and those originally from plains residing in high altitude areas in Ladakh. RESULT: There were 24% individuals with TBUT of < 5 seconds, 30% between 6-10 seconds and 46% with TBUT of > 10 seconds. In symptomatic patients with TBUT of <5 seconds, eight cases had irritation of eyes, six foreign body sensation and two cases had pain, watering, irritation and redness of eyes. Pterygium was seen in 12 individuals and inter palpebral congestion in 4 cases. CONCLUSION: A total of 24% cases showed abnormal (<5 seconds) TBUT. Abnormality of tear film in the presence of low humidity and windy condition with high ultraviolet radiation may lead to ocular discomfort and pterygium in these areas. PMID- 27408179 TI - Growth in Children with Steroid Sensitive Nephrotic Syndrome. AB - BACKGROUND: Nephrotic syndrome in children usually has an onset between 2-8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS). METHODS: Data of 35 children with SSNS was analysed retrospectively. They were divided into two groups. Group I received prednisolone only and Group II received levamisole and or cyclophosphamide in addition to steroids. Their heights were recorded at the time of inclusion and again one year later. The SD scores for age were determined. Growth rate as a change in the SD score over one year (Delta SD score) was correlated to the cumulative dose of steroids over the same period using the Pearson's correlation. RESULT: There were 24 (68.6 %) boys and 11 (31.4 %) girls (M:F ratio 2.18:1) in the age group of 17 months to 11 years at inclusion. Group I constituted 19 (54.2 %) and Group II, 16 (45.8 %). Pearson's correlation coefficients for all children, Groups I and II were -0.341, -0.441 and -0.255 respectively indicating "Fair correlation". This indicates that as the cumulative dose of steroid increases the growth retardation becomes more apparent. CONCLUSION: Growth retardation is proportional to the cumulative dose of steroids in children with SSNS. PMID- 27408180 TI - Spectrum of Acute Viral Hepatitis in Southern India. AB - BACKGROUND: The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented. METHODS: A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features. RESULT: Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11-20 and 21-30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A. CONCLUSION: Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India. PMID- 27408181 TI - Maternal Factors for Low Birth Weight Babies. AB - BACKGROUND: Low birth weight is defined as the live births with less than 2.5 kg weight. It is a key determinant of infant survival, health and development. Low birth weight infants are at a greater risk of having a disability and for diseases such as cerebral palsy, visual problems, learning disabilities and respiratory problems. To reduce the low birth weight deliveries, we studied the maternal factors which adversely affect the fetus in utero and their impact on fetus. METHODS: A retrospective study was carried out on 40 low birth weight pregnancies out of 650 deliveries from July 2005 to Jun 2006. Maternal factors like age, parity, pre pregnancy body mass index, hemoglobin levels, bad obstetric history (history of stillbirth/neonatal death in previous pregnancies, three or more spontaneous consecutive abortions), pre eclampsia, fetal distress, mode of deliveries were studied. These results were compared with a random sample of 300 pregnant ladies taken from rest of the deliveries. Cases of multiple pregnancies and stillbirths were excluded. RESULT: We found that prepregnancy maternal body mass index (p<0.01 for BMI <20), unbooked status (p<0.01), pre eclampsia (p <0.01) and bad obstetric history (p<0.01) were the maternal factors which resulted in low birth weight babies in most of the cases. However in 10 (25%) cases, no contributory maternal factor was found. CONCLUSION: Prepregnancy maternal body mass index, unbooked status, pre eclampsia and bad obstetric history are significant maternal factors resulting in low birth weight babies. PMID- 27408182 TI - Hepatitis B Immunisation in Health Care Workers. AB - BACKGROUND: Hepatitis B virus (HBV) infection is an important occupational risk in health care workers (HCW). In spite of HBV vaccine availability in Armed Forces, the high prevalence of HBV infection in HCW continues to be a problem. The study was undertaken to study the HBV vaccine-compliance among HCW. METHODS: A cross-sectional study was conducted at a tertiary care hospital. HCW were requested to fill up the pre set questionnaire to assess the HBV vaccination coverage. RESULT: Amongst 254 HCW, only 57.7% were vaccinated against HBV. The vaccine compliance was lowest among housekeeping professionals. The mean age at vaccination was high (30.5 years). Amongst the vaccine non-compliant subjects, 34.3% were above 30 years of age. 32.2% HCW completed primary vaccination after spending more than 10 years in the profession. Accessibility of HBV vaccine, knowledge and perception of HBV risk were important factors in vaccine non compliance. CONCLUSION: Due to low and delayed HBV vaccine-compliance, HCW continue to be at the risk of occupational HBV. Health education highlighting occupational risk of HBV, accessibility of vaccine and mandatory vaccination of HCW is recommended to increase HBV vaccine compliance among HCW. PMID- 27408183 TI - Renal Transplantation: Experience at a Single Centre. AB - BACKGROUND: Renal transplantation program in the Armed Forces commenced in Feb 1991 and till date 245 patients have undergone renal transplantation at INHS Asvini. We describe our protocols for donor and recipient evaluation and immunosuppression. METHODS: 245 patients received renal transplants during this period, 243 (99.2%) being from live donors. Most of them were started on triple immunosuppression comprising of cyclosporine, azathioprine and prednisolone. Newer drugs like mycophenolate, tacrolimus and sirolimus were administered in a select population. RESULT: 69 (28.1%) of them had at least one episode of acute rejection, most of which were steroid responsive and 13 (18.8%) of them required either anti CD3 monoclonal or anti-thymocyte globulin (ATG). Complete recovery with normal renal function occurred in 54 (78.2%) cases and 15 (21.7%) recovered with residual dysfunction with maximum serum creatinine being 2.1mg/dl. There were three (1.2%) cases of accelerated rejection during the first week of transplantation and one had graft rupture. All three lost their grafts. There were eight (3.2%) cases of acute tubular necrosis, who recovered completely within 8-14 days. Immediate infections included wound sepsis, lower respiratory tract infection, disseminated candidiasis and disseminated aspergillosis. Late infections included pulmonary tuberculosis, disseminated tuberculosis, cytomegalovirus infection and recurrent urinary tract infection. 28 (11.4%) patients developed post transplant diabetes mellitus. At the end of one year and five years, graft and patient survival were 97.2%, 93%, 80.9% and 85.7% respectively. CONCLUSION: Our outcomes show that the transplantation is a viable mode of renal replacement therapy in patients of end stage kidney disease with a near normal rehabilitation. PMID- 27408184 TI - External Versus Endoscopic Dacryocystorhinostomy: A Retrospective Study. AB - BACKGROUND: External dacryocystorhinostomy (DCR) has been the standard surgery for nasolacrimal duct obstruction before the development of endoscopic DCR. METHODS: This retrospective study included 103 patients with 109 cases (6 cases with bilateral disease) of nasolacrimal duct obstruction, of which 55 were treated with external DCR and 54 with endoscopic DCR. They were followed up for a minimum period of six months for surgical outcome. RESULT: The mean age of the patients in both the groups was 30 years. The success rate defined as absence of epiphora in the external DCR group was 90.9% and 95 % in the endoscopic DCR group. Majority of the recurrence, 5 out of the 6 (83.3%) in the external DCR group occurred in the first two months of surgery, while one reported four months after the surgery. The problem of intraoperative hemorrhage encountered in the external DCR group was not faced in the endoscopic DCR group. Revision of DCR was indicated in 9.1 % of cases in external DCR group as compared to 5.5 % in the endoscopic group. Serious complications like keloid formation and cosmetically unacceptable scar were not noticed in the external DCR group. Cerebrospinal fluid (CSF) rhinorrhoea was not encountered in the endoscopic group. CONCLUSION: Both the external DCR and the endoscopic DCR are effective surgical approaches for nasolacrimal duct obstruction with comparable success rate. PMID- 27408185 TI - Study of Disorders of Visual Acuity among Adolescent School Children in Pune. AB - BACKGROUND: Disorders of visual acuity are known to affect the learning abilities of school children. Various authors have reported varying prevalence in India and abroad. METHODS: A rapid, community based survey was conducted to assess the prevalence of disorders of visual acuity among adolescent school children in three schools in Pune Cantonment. A sample of 236 children studying in six sections were examined after random selection by a two stage sampling technique ensuring representation to each of the classes. Visual acuity was assessed for all the children available in the selected section on the date of survey. A questionnaire based study of the knowledge and attitude of the parents of the 50 affected children was also conducted. RESULT: 50 children (25 males and 25 females) were found to have errors of refraction, resulting in prevalence rate of 21.19% with confidence intervals of 15.97% to 26.40%. CONCLUSION: The study highlights significantly high prevalence of uncorrected errors of visual acuity among adolescent school children as well as the need for instituting IEC activities aimed at improving the general lack of appreciation of the seriousness of the problem by the parents and consequent neglect of urgent corrective measures. PMID- 27408186 TI - Blood Transfusion Practices in Military Medicine. AB - BACKGROUND: This observational study was conducted in a small, 45 bed border static hospital, located in a field area, where no blood bank facilities were available. The present study was conducted to elucidate the blood transfusion practices of this hospital. METHODS: A retrospective analysis of all blood transfusions performed in this hospital between Dec 2004 and Dec 2006 was carried out. The data collection included blood group patterns, common indications, haemoglobin levels and complications of blood transfusion. Inferences were based on available data and relevant statistical analysis. RESULT: A total of 246 blood transfusions were administered to 79 recipients during the study period. Only one patient had an Rh negative blood group. The most frequently transfused blood group was A Rh positive. Majority of transfusions were administered to surgical cases and the commonest indication was gunshot wounds with haemorrhagic shock. The mean haemoglobin at admission was 8.93 g/dl. The mean number of blood transfusions per patient was 3.13. No haemolytic or other transfusion reactions occurred in any of the transfusions. CONCLUSION: This study demonstrates that blood transfusions can be safely administered in field conditions despite constraints of not having a blood bank. PMID- 27408187 TI - Cation Exchange High Performance Liquid Chromatography for Diagnosis of Haemoglobinopathies. AB - BACKGROUND: Cation exchange high performance liquid chromatography (HPLC) is emerging as the method of choice for initial screening and diagnosis of haemoglobinopathies. The use of alkaline and acid gel electrophoresis in the developing countries may result in incorrect diagnosis of haemoglobinopathies. The aim of the study is to assess the accuracy and precision of diagnosis of haemoglobinopathies by HPLC and its possible advantage over conventional techniques. METHODS: Over a two year period, 955 patients presenting with anaemia were evaluated by HPLC for diagnosis of haemoglobinopathies. All cases showing 'unknown peaks' and other rare haemoglobin variants on HPLC were further analyzed by agar gel electrophoresis at alkaline pH (8.6) and at acid pH (6.0). RESULT: A total of 137 (14.3%) patients showed different abnormal haemoglobins variants. Of these 91 (66.4%) were diagnosed to have beta - heterozygous thalassaemia based on high level of HbA2 (>3.9%), five (3.7%) as beta - homozygous thalassaemia (HbF 25 - 91%), 15 (10.9%) as sickle cell trait, two (1.5%) as compound heterozygous state of sickle - beta(+) thalassaemia and three (2.2%) patients as homozygous sickle cell anaemia (HbSS). One (0.7%) patient had unknown peak on HPLC with retention time of 4.78 minutes, constituting 16.8% of total haemoglobin. Sickling test was negative. He was diagnosed as HbQ - India heterozygous. Thirteen (9.5%) patients were diagnosed as HbE syndrome and were further sub classified as HbE trait (five cases) and HbE disease (eight cases). Seven (5.1%) patients were diagnosed as Hb - D Punjab heterozygous. CONCLUSION: The simplicity of the sample preparation, superior resolution of the method and accurate quantitation of haemoglobin concentration, combined with complete automation, makes this an ideal methodology for diagnosis of haemoglobinopathies. PMID- 27408188 TI - Prevalence of Human T Cell Leukaemia Virus amongst Blood Donors. AB - BACKGROUND: Human T cell leukaemia virus (HTLV) I/II are retroviruses implicated in transfusion transmitted infection. Present study was undertaken to assess seroprevalence of HTLV in voluntary blood donors along with pattern of blood utilisation. METHODS: A total of 258 healthy blood donors who were free from infectious markers in transfusion as per current transfusion guidelines were enrolled. They were screened for HTLV-I/II antibodies by commercially available enzyme immuno assay (EIA) and their blood utilisation data was analysed. RESULT: Five (1.9%) donors were found seropositive for HTLV-I/II of which 1.2 % were first time and 0.9% were repeat donors. Blood utilisation data revealed 20.9% and 38.8% units were utilised within 5 and 6-14 days of collection respectively. 45.9% recipients were transfused with single blood unit. 42.9% recipients were immunosuppressed due to underlying disease. CONCLUSION: The high prevalence of HTLV in blood donors, coupled with single unit transfusion, use of fresh blood, non availability of acellular blood products and immunosuppression in recipients can lead to significant transfusion transmitted HTLV infection. We suggest judicious use of blood products and screening of blood donors in prevention of transfusion transmitted HTLV-I/II. PMID- 27408189 TI - Unknown Poisoning Amongst Serving Personnel. AB - BACKGROUND: Poisoning is recognized as an important health problem in many countries of the world. There is incomplete information on poisoning accidents, which is a major problem in developing countries. METHODS: A cross-sectional analysis of hospital records of armed forces personnel admitted with a provisional diagnosis of unknown poisoning was carried out. RESULT: Unknown poisoning represented 0.25% of hospital admissions and 6584 man-hours were lost. 85% poisonings occurred at railway station and majority were food related. Average length of stay in the hospital was 14.69 days. Ten patients required intensive care and two patients were admitted to the psychiatry ward. CONCLUSION: Majority of the incidents occurred in railways, signifying the importance of health education and precaution while proceeding on leave. Since, most of the affected were young soldiers, education should start from recruiting centers. Few patients had alcohol intoxication reflecting their dependence potential and need for reinforcing prohibition on alcohol consumption during travel. PMID- 27408190 TI - Chronic Kidney Disease in Children: An Indian Perspective. PMID- 27408191 TI - Diabetes Mellitus in India: The Modern Scourge. AB - India has a high prevalence of diabetes mellitus and the numbers are increasing at an alarming rate. In India alone, diabetes is expected to increase from 40.6 million in 2006 to 79.4 million by 2030. Studies have shown that the prevalence of diabetes in urban Indian adults is about 12.1%, the onset of which is about a decade earlier than their western counterparts and the prevalence of Type 2 diabetes is 4-6 times higher in urban than in rural areas. The risk factors peculiar for developing diabetes among Indians include high familial aggregation, central obesity, insulin resistance and life style changes due to urbanization. Screening for gestational diabetes and impaired glucose tolerance among pregnant women provides a scope for primary prevention of the disease in mothers as well as in their children. The problems of obesity and impaired glucose tolerance (IGT) (important predisposing factors) are not confined to adults alone but children are also increasingly getting affected. Most long standing macro and micro vascular complications are also more common among Indian diabetics as compared to other races and ethnic groups. A strong familial clustering of diabetic nephropathy among Indian Type 2 diabetics has also been noted. Clustering of cardiovascular risk factor like Syndrome X is common among urban Indians. The rising incidence of diabetes and its complications are going to pose a grave health care burden on our country. Timely effective interventions/measures and screening tests for complications at the time of diagnosis becomes imperative not only for early detection, but also to prevent progression to end stage disease. Screening for gestational diabetes among pregnant women would also go a long way in primary prevention of the disease. Life style changes/interventions and drugs like rosiglitazone are the current strategies that can prevent and/or delay the onset of diabetes. Simple interventional strategies like "Eat less, Eat on time and Walk more" can go a long way in preventing these chronic disorders among present as well as in the future generations. PMID- 27408192 TI - Frozen Red Blood Cells in Transfusion. AB - Red blood cells (RBCs) can be cryopreserved with shelf life of 10 years. However, shelf life of deglycerolized RBCs in conventional open system is just 24 hours, resulting in sporadic use of Frozen RBC (FS-RBC). Recently Naval Blood Research Laboratory (NBRL) method using ACP 215 (ACP(TM) 215 Haemonetics Cell Processing System) has been introduced, where shelf life of deglycerolized RBC is 14 days. FS-RBC unit is prepared from single blood donation, which needs to be glycerolized and deglycerolized. NBRL method using ACP 215 in FS-RBC is described. Deglycerolized unit weighed between 325-350 gm with haemoglobin of 15 18 gm/dl and freeze- thaw- wash RBC recovery of 87%. Transfusion of deglycerolized RBC offered advantages such as elimination of need of crossmatching in emergent situations and reduction of transfusion reactions. FS RBC by NBRL method using ACP 215 has advantages such as long shelf life, meeting unexpected high blood demand in mass casualties situations or availability of rare blood group requirement of individual patient. FS-RBC can be a potential candidate for Indian Armed Forces Blood programme for uninterrupted blood supply during peace and war. PMID- 27408193 TI - Recombinant Factor VIIA. PMID- 27408194 TI - Brain Attack : Time to Act Now. PMID- 27408195 TI - Radiological Quiz. PMID- 27408196 TI - Idiopathic Segmental Infarction of the Greater Omentum. PMID- 27408197 TI - Post Cricoid Web Excision. PMID- 27408198 TI - Bilateral Early Cataracts in Type 1 Diabetes. PMID- 27408199 TI - Frontal Mucocele causing Unilateral Proptosis. PMID- 27408200 TI - Meckel's Diverticulum with Mesodiverticular Band : An Unusual Presentation. PMID- 27408202 TI - Erratum. AB - [This corrects the article .]. PMID- 27408201 TI - Macular Hole Surgery : Maiden Experience. PMID- 27408203 TI - Fetal Anomalies in Rheumatoid Arthritis Patient Exposed to Low Dose Methotrexate. PMID- 27408204 TI - Papillary Carcinoma Thyroid in a Thyroglossal Cyst. PMID- 27408205 TI - Lupus Vulgaris with Abscess. PMID- 27408206 TI - Thanatophoric Dysplasia : Antenatal Diagnosis. PMID- 27408207 TI - Hepatic Rupture Complicating HELLP Syndrome in Pregnancy. PMID- 27408208 TI - Mycobacterium fortuitum Infections in Surgical Wounds. PMID- 27408209 TI - Attention to TEN. PMID- 27408210 TI - Toxic Epidermal Necrolysis Managed with Immunoglobulin: Reply. PMID- 27408211 TI - Paradigm Shift in Dental Sciences : Are We In It! PMID- 27408212 TI - Pattern of Fatal Injuries in Counter Terrorist Operations: An Innovative Analysis through Embalming Services. AB - BACKGROUND: Mortal remains of the soldiers killed in counter-terrorist operations in Kashmir valley are sent to their home after undergoing mandatory embalming. METHODS: Injuries on the mortal remains of the soldiers killed in counter terrorist operations between Jan 1999 to Dec 2006 were analysed with respect to the agent, mode of injury, age, rank structure, body parts involved, seasonal variations and changing trends. Fatalities consequent to enemy action across line of control and fatalities of Kargil war were also analysed for comparison. Statistical analysis was done using chi square test for difference in proportions. RESULT: Over the study period, terrorist induced injuries accounted for 8.16 deaths per thousand troops deployed whereas enemy action from across the line of control accounted for 0.63 deaths per thousand. Terrorist induced fatalities peaked in 2001 and thereafter revealed a declining trend ('p' < 0.001). Fatalities due to enemy action across line of control declined to zero since 25 Nov 2003 consequent to effective ceasefire. Of the total fatalities, 89.5% were killed in action (KIA) while 10.5% died of their wounds after reaching the hospital. Fatality to total injured ratio peaked to 29% in 2001 and than stabilized to about 23%. Mean KIA to total casualty ratio was 21%. The rank structure of the fatalities was officers 8.6%, JCOs 7.3%, and Other Ranks 84.1%. Most of the soldiers died young, 51% being below 25 years of age. Out of the terrorist induced fatalities, 78.2% died of gunshot wounds and 21.5% by splinters and improvised explosive devices (IED). The ratio was reversed in enemy induced fatalities and in Kargil war. Fatalities peaked during June to November and declined in winters. Body region wise, 23.4% of all deaths were due to head injury, 8.4% due to neck and maxillofacial injury, 18.4% due to injury to lungs and 11% due to heart injury. Most frequent target of the fatal bullet was brain (25.4%), closely followed by lungs (22.5%) and heart (12.3%). When soldier died of splinters / IED, multiple body parts were injured in 57.5%, brain in 17.3%, face & neck in 3.5%, heart in 6.6%, lungs in 5.3%, abdomen in 3.5% and limbs in 5.8%. Fatality due to head and heart injury peaked in 2001, while multiple injuries peaked in 2000, declined in 2001 and peaked again in 2004 and 2005 ('p' < 0.001). In fatalities of Kargil war, chest injuries were less but multiple injuries were more. CONCLUSION: Most of the fatalities were due to gunshot wounds selectively aimed at head, face, neck and thorax. Therefore, a lightweight flexible and effective bulletproof protection for this area will conserve manpower. PMID- 27408213 TI - Serum Serotonin Abnormality in Depression. AB - BACKGROUND: Serotonin plays an important role in treatment of depression. We evaluated the clinical correlates of plasma serotonin levels in depressed patients before and after treatment. METHODS: Study sample comprised of 40 patients diagnosed on ICD-10 diagnostic criteria, and an equal number of healthy matched controls. Subjects were evaluated on Beck's Depression Inventory (BDI) and Suicide Ideation Scale (SIS), before and after the treatment. Blood samples were collected from all the cases and controls before starting the antidepressant medication with selective serotonin reuptake inhibitors (SSRI's). Serum serotonin levels were measured before and after treatment. RESULT: Significant differences in scores before and after the intervention on BDI, SIS and serotonin levels of cases and controls (p<.000) were noted. Correlation between the serum serotonin levels before and after the treatment, and between the rating scales did not reveal significant association (p > 0.05). Patients with suicidal intentions had lower levels of serotonin. The scores changed after intervention. CONCLUSION: Treatment with SSRI's had shown significant changes in clinical conditions. However these changes did not relate significantly with serum serotonin levels. PMID- 27408214 TI - Laparoscopic Simulators : Are They Useful! AB - BACKGROUND: Laparoscopic surgery has changed the face of medical care forever. The benefits of laparoscopic open surgery have been demonstrated in virtually all major abdominal surgical procedures. Laparoscopy has introduced a new skill set that must be mastered and requires dedicated training. The teaching of laparoscopic operative skills in the clinical setting is constrained by the complexity of procedures, medicolegal and ethical concerns, fiscal and time limitations. This has created the need for formal training outside the operating room. Simulator-based training holds great promise in enhancing surgical education and providing a safe, cost-effective means for practicing techniques prior to their use in the operating room. METHODS: The surgical residents of two batches were recruited for the study. The residents were randomized to either a group that received training on a simulator or a controlled group that did not receive the training or to a group that received training twice. RESULT: The residents who received training on a simulator demonstrated better psychomotor skills in the operation theatre than those who did not. Training in simulator environment can contribute to the development of technical skills relevant to the performance of laparoscopic surgery in vivo. Training at regular intervals will benefit the residents in gaining significant improvement of their psychomotor skills. CONCLUSION: Laparoscopic trainer is a promising tool for training in laparoscopic surgery. PMID- 27408215 TI - Modifications to Increase Efficiency of the Begg Orthodontic Technique. AB - BACKGROUND: Orthodontic appliances that deliver results in a shorter time period without sacrificing the quality of the outcome are preferred. A modified fixed appliance, blending the merits of the Preadjusted Edgewise and Begg appliances was tested. METHODS: Thirty patients each were randomly assigned for treatment with one of the three fixed appliance techniques after qualifying for the inclusion and exclusion criteria established before the study. Peer assessment rating (PAR) index was used to compare the quality of treated cases. Total time as well as chairside time taken for treatment with the three techniques was also compared. ANOVA and paired student 't' test were used for statistical analysis. RESULT: There was a significant reduction in PAR scores with all the three appliances. There was no significant difference in the quality of treatment outcome between the Preadjusted Edgewise appliance (PEA) and the modified Begg appliance. These appliances gave a significantly better improvement as compared to the Begg appliance. Chairside and total time taken was the least with the modified Begg appliance followed by the PEA and Begg appliances. CONCLUSION: The suggested modification of the Begg appliance is efficient and economical as compared to PEA and Begg appliances in the treatment of cases with anterior teeth proclination as one of the elements of malocclusion. PMID- 27408216 TI - Role of Oral Appliances in the Management of Sleep Disorders. AB - BACKGROUND: A study was undertaken with the aim to evaluate the therapeutic and clinical efficacy of oral appliances in the management of upper airway sleep disorders like snoring and obstructive sleep apnea (OSA). METHODS: Oral appliances were prescribed in eight cases of non - apneic snoring and 42 polysomnography (PSG) diagnosed cases of OSA. The cases were assessed on Epworth Sleepiness Scale (ESS) and Apnea - Hypopnea Index (AHI). RESULT: 62.5% of the non - apneic snoring cases reported gross reduction/cessation of snoring. In the OSA cases, the mean AHI and ESS scores decreased from 51.48 +/- 23.70 to 32.78 +/- 18.06 and 12.50 +/- 3.57 to 7.20 +/- 2.917 respectively. A statistically significant (p<0.0001) improvement in AHI and ESS scores was observed. CONCLUSION: Short term therapeutic efficacy of oral appliances therapy in non apneic snoring and OSA cases was observed. PMID- 27408217 TI - Management of Zygomatic Complex Fracture in Armed Forces. AB - INTRODUCTION: The Armed Forces personnel are exposed to various kinds of injuries due to the nature of their duties. Increase in motorized population without taking protective measures and rise in violence has contributed towards maxillofacial injuries. The aim of this study was to determine the incidence, aetiology and management of injuries resulting in fracture of the Zygomatic complex in Armed Forces personnel and their families. METHODS: This study was conducted at Command Military Dental Centre (EC). Out of 90 maxillofacial injuries, 40 individuals (44.4%) were treated for Zygomatic complex fractures, majority were in their third decade of life and RTA was the leading cause. RESULT: Thirty seven individuals (92.5%) recovered uneventfully, while three (7.5%) patients had post operative complications such as enophthalmos, paraesthesia, diplopia, facial asymmetry, palpability of implants and facial nerve paresis. These complications were subsequently treated successfully. CONCLUSION: The midface is composed of fragile bones which get fractured easily. It is imperative to educate people regarding the use of protective headgears/seat belts while travelling in motorized transport. PMID- 27408218 TI - Effect of Antenatal Expression of Breast Milk at Term in Reducing Breast Feeding Failures. AB - BACKGROUND: Though breast feeding is natural, during the first 2-3 days, when enough breast milk is not available with mother, she may introduce bottle feeding erroneously for improving nutrition to her baby. We studied the effect of antenatal expression of breast milk at term in reducing breast feeding failure as compared to conventional method of initiation of breast feeding. METHODS: A prospective study was carried out in 180 booked cases at term. Daily expression of breast milk at least once a day after 37 weeks of pregnancy was introduced in randomly selected 90 pregnant ladies. Prior examination was done to exclude any inverted or cracked nipples and appropriate treatment instituted. RESULT: The study group who expressed breast milk daily after 37 weeks did not find it difficult to initiate breast feeding after vaginal or cesarean delivery. Sufficient milk started flowing within half an hour of initiation of breast feeding in most 85 (94.4%) subjects of study group as compared to 63 (70%) patients of control group, which was statistically significant. There was no increase in any delivery complication. There were two partial breast feeding failures in control group but none in study group. CONCLUSION: Daily antenatal breast milk expression after 37 completed weeks of pregnancy significantly reduced the time for establishing full breast feeding and reduced breast feeding failures. PMID- 27408219 TI - Primary 360 degrees Broad Buckling in Retinal Detachment. AB - BACKGROUND: Chronic rhegmatogenous retinal detachment behaves like proliferative vitreo-retinopathy (PVR) even without evidence of the same. Surgery could be done either with conventional buckling procedures where the extent of buckling is determined by the number and location of the breaks or by primary vitreous surgery. In this study these cases were managed with primary 360 degrees encircling broad buckle without a vitreous procedure. METHODS: 210 eyes, with rhegmatogenous retinal detachment of more than six months duration and with PVR up to C3 (CP3 focal) were subjected to buckling surgery. Trans-scleral cryopexy of the breaks, 360 degrees encircling buckle with a 276 - 279 tire and subretinal fluid drainage was performed. RESULT: Most (85.74%) of the eyes showed anatomical retinal re-attachment. CONCLUSION: Primary broad encircling buckling can be conducted successfully in cases of long standing retinal detachment. PMID- 27408220 TI - Study of Single Donor Platelet (SDP) Preparation by Baxter CS 3000 plus and Haemonetics MCS plus. AB - BACKGROUND: In plateletpheresis blood is withdrawn from a donor in anticoagulant solution and separated into components. Platelets are retained and the remaining components are returned to the individual. METHODS: The present study was aimed to compare the platelet yield and collection efficiency of Baxter CS 3000 plus and Haemonetics MCS plus cell separators and to study adverse donor reactions. Donors were selected as per the set criteria for single donor platelet (SDP) preparation. Donors' samples for pre donation and post donation platelet count were collected in EDTA and for product counts in the sample pouch attached with apheresis kits. The results were obtained by haematology analyzer. Platelet yield and collection efficiency were calculated. RESULT: Results were tabulated for both the cell separators and analyzed. Platelet yield was marginally better with Baxter CS 3000 plus but collection efficiency was better with the Haemonetics MCS plus. Residual white cells were more in single donor platelet concentrate preparation by MCS plus. Adverse donor reactions were similar with both cell separators, in form of mild citrate toxicity and mild to moderate pain at phlebotomy site. CONCLUSION: Findings of the present study along with other factors such as less priming time for kit, portability of cell separator, better patient comfort owing to single arm venous access and lesser cost suggest that Haemonetics MCS plus is a better choice as compared to Baxter CS 3000 plus cell separator. PMID- 27408221 TI - Midline Fractures in Single Maxillary Complete Acrylic vs Flexible Dentures. AB - BACKGROUND: Patients using single maxillary denture against their natural mandibular teeth face the problem of midline fracture in their routine acrylic dentures. Various techniques have failed over the years to address the problem. In this study, flexible denture material (Lucitone) with injection moulding system has been used and evaluated for midline fracture in these patients. METHODS: A total of 58 patients in the age group of 38 to 80 years, who had experienced midline fracture in their acrylic maxillary dentures were selected. They were provided with new dentures using flexible denture material. Various parameters, namely, mastication, phonetics, esthetics and comfort level were evaluated. RESULT: Only two cases reported slight crack in the palatal region of the-maxillary dentures after 18 months of use. Mastication and phonetics were found to be improved with flexible dentures. CONCLUSION: The flexible denture is a promising material for preventing midline fractures in a single maxillary denture. It is well tolerated by the patients as compared to the methyl meth acrylate dentures. PMID- 27408222 TI - Marginal Accuracy of Castings Produced with Different Investment Systems. AB - BACKGROUND: The use of casting ring to produce accurate castings has been challenged with the introduction of a ringless casting technique. This study compared the marginal accuracy of all - metal complete coverage crowns fabricated with ringless, split plastic ring and metal ring investment systems. METHODS: A total of 40 all- metal complete coverage crowns were fabricated on a metal die. The crowns were divided in 4 groups (Group A, B, C and D) of 10 patterns each. A ringless system of investing and casting was used for group A whereas a split plastic ring system was used for group B. Groups C and D utilized metal ring with single and double layers of asbestos free cellulose acetate liner respectively for investing and casting procedures. The restorations were seated on the metal die and the vertical marginal discrepancy was evaluated by measuring the gap between the finish line on the die and the margins of the crown on four specific sites with an optical microscope. Statistical analysis was carried out using ANOVA and multiple comparison "t" test. RESULT: The mean vertical marginal discrepancy for groups A, B, C and D was 95MUm, 136MUm, 128MUm and 104MUm respectively. Vertical marginal discrepancy on each surface was compared among the four groups. Difference of vertical marginal discrepancy on buccal surface (p<0.0001) as well as distal surface (p<0.005) was highly significant whereas it was non-significant on lingual and mesial surfaces (p>0.05). CONCLUSION: Accurate castings with better marginal fit can be produced with ringless casting technique. PMID- 27408223 TI - Maxillary Expansion in Cleft Lip and Palate using Quad Helix and Rapid Palatal Expansion Screw. AB - BACKGROUND: Management of patients with cleft lip and palate (CLP) includes orthodontic treatment prior to bone grafting. Palatal expansion is done using slow or rapid palatal expansions (RPE). Controversy still exists regarding choice of expansion appliances used. This study was conducted to find out whether the Quad helix appliance represents a reasonable alternative to using conventional rapid maxillary expansion appliance among cleft lip and palate patients. METHODS: Twenty cleft lip and palate patients had orthodontic study models taken prior to expansion and at the end of expansion. There pre and post treatment study models were analyzed for changes in intermolar width, molar tipping and molar rotation. RESULT: The difference in molar tipping, increase in intercanine and molar width between slow palatal expansion (SPE) and rapid palatal expansion (RPE) group was not statistically significant. A difference between the two groups was found in the ability to rotate molars. CONCLUSION: The clinical findings suggest that maxillary expansion using the Quad helix appliance represents a reasonable alternative to using conventional rapid maxillary expansion appliances among cleft patients. PMID- 27408224 TI - Organ Donation : Intensive Care Issues in Managing Brain Dead. AB - Organ donation and transplantation is one of the most powerful and dramatic practices in modern medicine. It is the pinnacle of centuries of dreams, massive amounts of accrued knowledge and impressive technical developments. One organ donor has the potential of saving more than five lives and impacting the quality of life of many others via tissue donation. The clinical team has a responsibility to the donor families and the recipient patient to do everything possible to provide best practices supported by the best evidence. These standardized best practices should come from the published evidence which is adapted for use in the specific environment, culture, and infrastructure of the institution. PMID- 27408225 TI - Sedation Guidelines for Gastro Intestinal Endoscopy. AB - Effective sedation is usually a vital precursor to any successful endoscopic procedure. With advanced techniques and medications available today this component of the procedure can be dealt with safely and in an efficient manner. PMID- 27408226 TI - Children in Conflict Zones. AB - The nature of war has changed dramatically. Today's conflicts happen where people live and they take a brutal toll on children. Heavy bombardment and destruction in war creates a humanitarian crisis where there is lack of adequate food, clean water and medicine. The consequences of war can have major impact on the health of children for years to come. Traumatic events can have a profound and lasting impact on the emotional, cognitive, behavioral and physiological functioning of an individual. Depending on the circumstances, the psychosocial impacts of disasters can range from mild stress reactions to problems such as anxiety, depression, substance abuse and post traumatic stress disorders (PTSD). PMID- 27408227 TI - The Highest Battlefield of the World : Medical Problems and Solutions. AB - The Indian Armed Forces Medical Services has been engaged in providing medical to the soldiers serving on Siachen Glacier for the last 25 years. This paper attempts to highlight the medical problems faced by troops on the world's highest battlefield as perceived by a medical officer located on the forward most medical echelon on Siachen Glacier. The medical problems on the glacier include high altitude pulmonary oedema, acute mountain sickness, frost bite chilblains, hypothermia, snow blindness, injury non enemy action due to avalanches, crevasses and fires, carbon monoxide poisoning and problems in disposal of nightsoil. A large number of problems are taken care of by following a well documented acclimatisation drill. However under such conditions providing medical support is a difficult task and requires innovations and improvisations entailing a high degree of mental mobility on the part of medical commanders and the Regimental Medical Officers located on the forward posts. PMID- 27408228 TI - Vitoss Synthetic Cancellous Bone (Void Filler). PMID- 27408229 TI - Methyl Prednisolone in Spinal Cord Injury : Is the Sheen Fading? PMID- 27408230 TI - Radiological Quiz. PMID- 27408231 TI - Interstitial Incisional Hernia following Appendectomy. PMID- 27408232 TI - Lumbar Hernia. PMID- 27408233 TI - Primary Iliac Bone Hydatid Disease : An Unusual Presentation. PMID- 27408234 TI - Cases of Beckwith-Wiedman Syndrome. PMID- 27408235 TI - Post Obstructive Pulmonary Edema Following Attempted Suicide by Hanging. PMID- 27408236 TI - Swyer's Syndrome : An Uncommon Cause of Primary Amenorrhoea. PMID- 27408237 TI - Congenital Hypoplasia of Depressor Angularis Oris Muscle. PMID- 27408238 TI - Management of Bilateral Impacted Maxillary Canines. PMID- 27408240 TI - Pediatric Nephrology Experience in Afghanistan. PMID- 27408239 TI - Gastric Stromal Tumour presenting as Upper Gastrointestinal Bleed. PMID- 27408241 TI - Gastric Stromal Tumour presenting as Upper Gastrointestinal Bleed: Reply. PMID- 27408242 TI - Mid- Clavicular Fractures- A Change in Treatment Strategies? PMID- 27408243 TI - Iatrogenic Amputation of the Great Toe. PMID- 27408244 TI - Mid- Clavicular Fractures- A Change in Treatment Strategies?: Reply. PMID- 27408245 TI - Obesity : More Than Meets The Eye. PMID- 27408246 TI - Impact of Body Mass Index on Left Ventricular Function. AB - BACKGROUND: Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on echocardiographic indices of systolic and diastolic left ventricular function. METHODS: Fifty one obese and 25 normal weight, serving personnel without any other pathological condition were studied. Group I (n=25) consisted of subjects with normal weight and body mass index (BMI <25kg/m(2)), Group II (n=34) of overweight subjects (BMI 25-29.9 kg/m(2)) and Group III (n=17) of obese subjects (BMI >30 kg/m(2)). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by >= 2 SD from the normal weight group. RESULT: Ejection fraction, fractional shortening were increased (p<0.05) in Group II and III. Left ventricular dimensions were increased (p< 0.001) but relative wall thickness was unchanged. Systolic dysfunction was not observed in any of the obese patients. The mitral valve pressure half time (p< 0.01), left atrial diameter (p < 0.01) and the deceleration time were increased (p< 0.01) in obese subjects, while other diastolic variables were unchanged. No difference were found between obesity subgroups. Subclinical diastolic dysfunction was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function. CONCLUSION: Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI. PMID- 27408247 TI - Exclusive Breast Feeding in Low Birth Weight Babies. AB - BACKGROUND: Human milk is the ideal source of nutrition for full term neonates, but there is controversy regarding its use as a nutrition source for preterm and low birth weight infants. However current data supports the use of human milk for low birth weight infants. This study was undertaken to evaluate the growth of both preterm and term small for gestational age infants nursed on exclusive breast milk from birth to four months of age. METHODS: This was a prospective, longitudinal study carried out in a recognized baby-friendly hospital where exclusive breast-feeding is practiced in all neonates. All consecutive low birth weight neonates irrespective of gestational age, born during the study period of two years were included in the study. Assessment of growth parameters included recording of weight (daily when in the hospital and later weekly), length (weekly) and head circumference (weekly) till the age of four months. RESULT: Low birth weight infants, both the preterm and the term small for gestational age, on being exclusively breastfed by their own mothers, gained weight and had an increase in their head circumference and length to the levels almost comparable to the standard fetal- infant growth norms. CONCLUSION: Exclusive breast-feeding results in adequate growth in low birth weight babies including preterms. PMID- 27408248 TI - Beyond Beauty : Botulinum Toxin Use in Anal Fissure. AB - BACKGROUND: Chronic fissure in ano is a common distressing problem with high recurrence rates. Any treatment modality should be simple, effective and reversible with no permanent sequelae. Long term medical management with poor compliance or surgical therapy with risk of incontinence are both less than ideal. In this scenario chemical sphincterotomy using Botulinum toxin offers an alternative modality. METHODS: A total of 30 patients of chronic fissure in ano were treated with Botulinum toxin injection in the internal sphincter. RESULT: All patients had significant symptomatic relief with high rates of fissure healing. The simplicity of administration, lack of complications and cost effectiveness make it a useful alternative to the currently practiced approaches. CONCLUSION: Botulinum toxin offers a simple outpatient treatment of chronic fissure in ano, which is safe, cost effective and reversible without significant complication. It has the potential of being used as a first line treatment in chronic fissure in ano. PMID- 27408249 TI - Adrenaline, Noradrenaline and Dopamine Level Estimation in Depression : Does it Help? AB - BACKGROUND: Abnormalities of catecholaminergic function have been hypothesised in causation of depressive illness. Electroconvulsive therapy (ECT) is postulated to have noradrenergic mechanism of action. We studied the clinical utility of estimating catecholamines level changes after ECT. METHODS: Plasma adrenaline, noradrenaline and dopamine in healthy controls and depressed patients were estimated by high performance liquid chromatography with electrochemical detection method before and after ECT. RESULT: Mean +/- standard deviation of plasma adrenaline, noradrenaline and dopamine in controls was 36.7 +/- 13.2, 209.3 +/- 76, 21.8 +/- 9.5 ng/L respectively, while in depressed patients before and after ECT it was found to be 32.5 +/- 12.0, 419.3 +/- 167.7, 22.1 +/- 16.0ng/ L and 37.2 +/- 19.6, 386.1 +/- 168.4, 22.3 +/- 15.5ng/L respectively. Correlation of adrenaline, noradrenaline and dopamine concentration with scores of Beck Depression Inventory, Suicidal Ideation Scale and Melancholia Inventory was positive but statistically not significant and poor. Based on the cut off values of noradrenaline, only 62% cases could be categorized as abnormal, which after ECT reduced to 50%, whereas post ECT psychiatric ratings was normal in about 78% cases. CONCLUSION: There is no clinical significance of estimating adrenaline, noradrenaline and dopamine in depressed patients. PMID- 27408250 TI - Urodynamic Changes in Pelvic Organ Prolapse and the Role of Surgery. AB - BACKGROUND: Pelvic organ prolapse (POP) is a major health problem of the "elderly" lady. The urological changes associated with POP and the beneficial effects of surgery on these changes continues to be controversial. We studied the urodynamic changes in POP and the effect of definitive surgery on these changes. METHODS: A total of 50 cases of POP, over a two year period, were subjected to urodynamic studies both pre and postoperatively and the data analyzed, to ascertain the effect of surgery on the urological profile of a patient with POP. RESULT: Four of the 50 patients studied had demonstrable stress urinary incontinence and two of these benefited significantly after surgery. In addition it was observed that four new patients developed stress urinary incontinence (SUI) postoperatively. It was also observed that the values of Qmax significantly improved after surgery from 9.2ml/s to 18.6ml/s. CONCLUSION: Definitive surgery improves the urological profile of the patient with POP, to a certain extent. A good clinical examination of patients with POP from the urological viewpoint, is essential preoperatively, to pick up the patients who are likely to develop stress incontinence postoperatively, so that corrective action can be initiated during surgery. PMID- 27408251 TI - Evaluation of Posterior Capsular Opacification following Phacoemulsification, Extracapsular and Small Incision Cataract Surgery. AB - BACKGROUND: Posterior capsular opacification is the most common complication of modern cataract surgery. METHODS: A prospective study was conducted on 150 patients (150 eyes) out of which 50 eyes each underwent cataract surgery by extracapsular cataract extraction, small incision cataract surgery and phacoemulsification technique. On postoperative follow up posterior capsular opacification and Neodymium: Yttrium Aluminium Garnet laser capsulotomy rate was evaluated. RESULT: Posterior capsular opacification rate was significantly less (p=0.03) in eyes which had undergone phacoemulsification as compared to extracapsular cataract extraction. However capsulotomy rate was not statistically significant after comparison of the three surgical techniques of cataract surgery. CONCLUSION: Posterior capsular opacification following cataract surgery can be minimized by the use of small incision cataract surgery and phacoemulsification. PMID- 27408252 TI - Extracorporeal Fixation of Displaced Mandibular Condylar Fracture : Viable Option. AB - BACKGROUND: To present a series of eighteen cases of displaced mandibular condylar fracture managed by extra-corporeal fixation. To evaluate the post operative results in terms of occlusal stability, temporomandibular joint function and radiological findings. METHODS: A series of 18 cases were treated with extra corporeal fixation with mini plate and screws for displaced mandibular condylar fracture. Ramus was exposed through sub mandibular approach. A wire was passed through the angle of mandible to pull the mandible inferiorly. The displaced condyle was retrieved. A suitable bone plate was fixed to the condylar segment and it was repositioned and stabilized with screw with the distal segment. In three cases vertical sub-sigmoid osteotomy was carried out to retrieve the condylar head. After assembling the osteotomised segment and condylar segment, it was repositioned and stabilised in predetermined position. Post operatively the patients were on inter maxillary fixation for a week followed by active physiotherapy. RESULT: The follow up period was between 2-11 years. In nine cases occlusion and mandibular function was good. There was no resorption of the condylar head. One case had complete resorption of the condylar head. Other case had fracture of the bone plate. CONCLUSION: Extracorporeal fixation is an effective method for management of displaced and dislocated condylar fracture. PMID- 27408253 TI - Study of Disabled Treated at Artifical Limb Centre. AB - BACKGROUND: Artificial Limb Centre (ALC), Pune provides comprehensive rehabilitation care to disabled soldiers of Armed Forces. A retrospective study of 16308 Armed Forces personnel treated at ALC, Pune was carried out to analyse the factors resulting in disability and their distribution among the soldiers. METHODS: Records of disabled soldiers treated at ALC, Pune from 14 May 1944 to 31 Dec 2003 were analysed with respect to their age, rank structure, nature of disability, causation and body part involved to find out various factors contributing to disablement and its distribution amongst the soldiers. RESULT: Trauma was the commonest cause of disability in Armed forces personnel and mine blast injury was the most frequent mode of trauma followed by road traffic accident. Study also revealed that lower limb amputation is the most common type of disability and below knee amputation is the most common level of amputation. Maximum disabled personnel were in the age group of 21 to 40 years and other ranks accounted for 92.58 % of the total number. CONCLUSION: War related injuries were the most common cause of disability in the Armed Forces personnel, which affect the young soldiers in their most productive period of life. PMID- 27408254 TI - Trends of Sexually Transmitted Infections : A 33 Year Experience. AB - BACKGROUND: Sexually Transmitted Infections (STIs) are a major public health problem the world over. This study was aimed at analyzing the trends of STIs in a 33 year period at a tertiary care service hospital. METHODS: A retrospective data analysis was done of all the cases diagnosed as STIs during a 33 year period from 1974 to 2006. RESULT: A total of 4532 STIs were seen in 4215 males. The commonest STI was chancroid (37.2%), followed by syphilis (16.2%). The commonest age group involved was the 21-30 year group (57.6 %). STIs declined from a total of 311 cases in 1974 to seven cases in 2006. This trend was mirrored in all major STIs. Multiple STIs were seen in 317 (07.5%) cases. CONCLUSION: The frequency of STIs has shown a distinctly decreasing trend from over the last 33 years. PMID- 27408255 TI - Retrospective Study on Efficacy of Intermaxillary Fixation Screws. AB - BACKGROUND: We evaluated the efficacy of intermaxillary fixation (IMF) screws in the treatment of mandibular fractures. METHODS: Two hundred patients with mandibular fractures, treated by IMF using these screws, were evaluated by pre and postoperative panoramic radiographs. Clinical testing was carried out for vitality and abnormal mobility of teeth adjacent to the site of screw insertions. Other factors such as possible iatrogenic dental injuries, loss, breakage or screw cover by oral mucosa and postoperative occlusion were also studied. RESULT: The most important complication noticed was iatrogenic damage to dental roots. CONCLUSION: Use of intraoral cortical bone screws for IMF is a valid alternative to arch bars in the treatment of mandibular fractures. Iatrogenic injury to dental roots is the commonest problem which can be minimized by an experienced surgeon. PMID- 27408256 TI - Food Poisoning Outbreak in a Military Establishment. AB - BACKGROUND: An outbreak of food poisoning involving 121 persons of a military establishment was investigated. METHODS: On investigation, a total of 94 persons became ill, with an attack rate of 77.7%. The symptoms included nausea, vomiting, abdominal pain, diarrhoea, weakness and fever. The mean incubation period was 2.3 hours while the median was 1.7 hours. Retrospective cohort study incriminated raita as the food item responsible for the outbreak, with a risk ratio of 21.35. Left over food was not available for laboratory analysis. There were no deaths and all affected persons recovered within 24 hours. RESULT: Coagulase positive staphylococci were cultured from the vomitus and stool samples of cases. Nasal and fingernail swabs collected from food handlers also showed staphylococcal growth. The most likely cause of contamination of raita with the enterotoxin could be the staphylococci which had colonised the bodies of food handlers. CONCLUSION: The aggravating factor was the storage of raita at room temperature before its consumption, which provided ideal conditions for enterotoxin formation. PMID- 27408257 TI - Local Drug Delivery with Tetracycline Fiber : An Alternative to Surgical Periodontal Therapy. AB - BACKGROUND: Scaling and root planing is the basic treatment modality for periodontal disease. Mechanical treatment is limited by physical impediments and biochemical considerations. Antimicrobial agents may be used as an adjunct to overcome limitations of mechanical therapy. METHODS: A case-control study was carried out on 30 patients suffering from chronic periodontitis. In Group A only scaling and root planing was carried out whereas in Group B tetracycline fibers were used along with scaling and root planing. RESULT: Tetracycline fibers as an adjunct to scaling and root planing was found to be more effective in reducing inflammation. The number of sites with bleeding on probing were 12 in Group A as compared to four in Group B after 30 days. The mean decrease in probing depth was more in Group B than Group A after 30 and 90 days. General linear model showed that decrease in probing depth was statistically significant with both mechanical therapy as well as adjunctive use of tetracycline fibers. CONCLUSION: Local drug delivery with tetracycline fiber is an effective and simple non surgical method to improve periodontal health which can be practiced even by a general dental practitioner. PMID- 27408258 TI - Prevalence of Noise Induced Hearing Loss in Indian Air Force Personnel. AB - BACKGROUND: Noise exposure is an inherent part of duty of the aircrew and maintenance staff in the Indian Air Force (IAF). An audiometric survey of IAF personnel was carried out to analyze the prevalence and severity of noise induced hearing loss (NIHL). METHODS: An audiometric study of 1000 IAF personnel of various trades, age and exposure groups were carried out at an operational base. Age related correction of 5 dB per decade was applied for personnel above SO years of age. Personal factors like smoking, blood group and use of ear defenders were analysed for their effect on the prevalence of NIHL. RESULT: The study revealed an overall incidence of NIHL of 22.9 % in the personnel with a higher prevalence among the technical trades (26.18 %) as compared to non technical trades (12.5 %). There was a significant increase in prevalence of hearing loss with duration of exposure with 50.8% of personnel above 30 years of exposure having hearing loss. A higher incidence of hearing loss was observed in personnel of blood group O and smokers whereas use of ear defenders was protective. CONCLUSION: The study reveals a significantly increased prevalence of NIHL among the technical trades of the IAF personnel. The deleterious effects of smoking and protective effect of regular use of ear defenders are emphasized. PMID- 27408260 TI - Natural Orifice Transluminal Endoscopic Surgery: Reality or Myth? PMID- 27408259 TI - Seroprevalence of Cytomegalovirus among Voluntary Blood Donors. AB - BACKGROUND: Primary cytomegalovirus (CMV) infection in immunocompetent host is self limiting infection, leading to latency of virus. However congenital CMV and CMV infections in immunocompromised patients are associated with high morbidity and mortality. Transfusion transmitted-cytomegalovirus (TT-CMV) infection in low birth weight neonate and immunocompromised transfusion recipients is being increasingly reported. Studies recommended transfusion of CMV free or CMV safe blood in prevention of TT-CMV. In this background, the study was undertaken to assess the CMV seroprevalence in blood donor. METHODS: A prospective study was conducted in which 431 voluntary blood donors were screened for CMV IgG and IgM by EIA (Enzyme Immuno Assay). RESULT: A total of 379 (87.9 %) voluntary blood donors were seropositive for CMV IgG. There was no statistical difference of CMV seropositivity and age. Further, seven (1.6%) subjects were both CMV IgM and IgG seropositive. CONCLUSION: High seroprevalence of CMV in our donor population is a threat to the blood safety. Strategies in reducing the risk of TT- CMV are discussed. Use of prestorage leucodepleted 'CMV safe' blood components along with judicious use of blood is recommended in prevention of TT-CMV in high risk recipients. PMID- 27408261 TI - WHONET Software for the Surveillance of Antimicrobial Susceptibility. AB - Continuous surveillance of local antimicrobial susceptibility patterns is a must for combating emerging antimicrobial resistance. WHONET is an effective computerized microbiology laboratory data management and analysis program that can provide guidance for empiric therapy of infections, alert clinicians of trends of antimicrobial resistance, guide drug-policy decisions and preventive measures. The program facilitates sharing of data amongst different hospitals by putting each laboratory data into a common code and file format, which can be merged for national or global collaboration of antimicrobial resistance surveillance. The system can be implemented in hospital laboratories of Armed Forces at no additional cost. Cumulative analysis of surveillance data obtained from various hospitals of Armed Forces at higher centers may help in formulating health policies and control measures at various levels. PMID- 27408262 TI - Pathological Quiz. PMID- 27408263 TI - Patient Transport Unit for Aeromedical Evacuation. PMID- 27408264 TI - Intra Abdominal Cystic Lymphangioma in an Adult. PMID- 27408265 TI - Pregnancy with HPV associated Viral Warts. PMID- 27408266 TI - Amniotic Band Disruption Sequence. PMID- 27408267 TI - Differential Diagnosis for Acute Appendicitis: Epiploic Appendagitis. PMID- 27408268 TI - A Case of Primary Peritoneal Hydatidosis. PMID- 27408269 TI - Chickenpox Appearing in Previously Vaccinated Individuals. PMID- 27408270 TI - Focal Ectasia of Internal Jugular Vein. PMID- 27408271 TI - Hypothyroidism Presenting as Dilated Cardiomyopathy. PMID- 27408272 TI - Vaginal Agenesis in Mayer Rokitansky Kuster Hauser Syndrome. PMID- 27408273 TI - Ureter in Sliding Inguinal Hernia. PMID- 27408274 TI - Hearing Preservation in a Case of Acoustic Schwannoma. PMID- 27408275 TI - Melanoma : A Frequently Missed Diagnosis. PMID- 27408276 TI - Study of Disorder of Visual Acuity among Adolescent School Children in Pune. PMID- 27408277 TI - Voluntary and not replacement donors are safe! PMID- 27408278 TI - REPLY. PMID- 27408279 TI - Enteric Fever: Emerging Trends. PMID- 27408281 TI - Spectrum of Childhood Tuberculosis in BCG Vaccinated and Unvaccinated Children. AB - BACKGROUND: Childhood tuberculosis remains a major public health problem in India. We evaluated the impact of BCG vaccination on childhood tuberculosis and the underlying risk factors. METHODS: 100 consecutive children below 12 years diagnosed to have tuberculosis based on the WHO and IAP consensus statement were included in the study. RESULT: Majority(42%) of children with tuberculosis were below four years of age. History of contact with a case of tuberculosis was present in 41 cases. BCG scar was present in 77 cases indicating a poor coverage/uptake of BCG vaccination. Pulmonary form of tuberculosis was seen in 52 and extra pulmonary form in 41 cases. Tubercular lymphadenitis was seen in seven cases, of which more than 70 % were in BCG vaccinated group. There was no statistically significant difference in the type of tuberculosis (pulmonary or extra pulmonary) and BCG vaccination. In the extra pulmonary form, 13 children had neuro-tuberculosis, of which 66% were in BCG unvaccinated group, which was statistically significant (p=0.011). The underlying risk factors were poor socioeconomic status (62%), malnutrition (61%) and poor immunization coverage. CONCLUSION: Higher incidence of pulmonary tuberculosis in BCG vaccinated group was not statistically significant. However, high incidence of neuro-tuberculosis in BCG unvaccinated group was statistically significant. The underlying risk factors were poor socio-economic status, malnutrition and poor immunization coverage and should be taken into consideration in order to prevent morbidity and mortality due to tuberculosis in children. PMID- 27408280 TI - Urodynamic Management of Neurogenic Bladder in Spinal Cord Injury. AB - BACKGROUND: A spinal cord injury is devastating and produces profound changes in the life style of the individual and his family. It is difficult to predict bladder and sphincter behaviour on the basis of clinical somatic neurological deficits. METHODS: A prospective study of 100 spinal cord injury patients was conducted to establish a bladder management protocol. The urodynamic variables were assessed frequently. Clean Intermittent Catheterization (CIC) along with antimuscarinic drugs was instituted and response monitored. Nonresponders were offered Intradetrusor Botulinum toxin. RESULT: Spinal shock lasted for upto six months and only 8% could be converted to CIC during the acute phase. A total of 82% patients underwent three to four urodynamic studies which revealed an increase in cystometric capacity and a decrease in the maximum detrusor pressures. This lowered the incidence of incontinence episodes and prevented upper urinary tract damage. Botulinum toxin provided only temporary relief. CONCLUSION: Aggressive management of neurogenic bladder (NB) dysfunction is a crucial component of the rehabilitation programme for spinal cord injury patients. Repeated urodynamic studies are an essential aid in managing the evolving nature of the bladder dysfunction. Meticulous bladder management protocol can prevent upper urinary tract complications. PMID- 27408282 TI - Conventional Versus Endoscopic Powered Adenoidectomy: A Comparative Study. AB - BACKGROUND: Adenoidectomy is a commonly performed ENT surgery. It is conventionally performed using the curettage method. This present article aims to evaluate endoscopic powered adenoidectomy as an alternative. METHODS: Sixty consecutive cases requiring adenoidectomy were randomized into two groups of thirty each. Group A underwent conventional adenoidectomy using the curettage method and Group B underwent endoscopic assisted micro-debrider adenoidectomy. The parameters studied were intra-operative time, intra-operative bleeding and completeness of resection, collateral damage, post operative pain and recovery time. RESULT: Sixty cases of adenoidectomy were done using conventional surgery and powered endoscopic adenoidectomy in the study period from Aug 04 to Dec 05. The time taken in Group A (conventional surgery) varied from 22-39 minutes (95% Confidence Interval (CI) -27.7 - 30.9)and in Group B (powered endoscopic surgery) from 27-55 minutes(95% CI 36.6 - 41.9) (p<0.05). The average blood loss in Group A was 21 ml (range 10-50) as compared to 31.67 ml (range 10-60) in Group B (p<0.05). The resection was invariably complete in Group B whereas seven(23%) cases had more than 50% residual adenoid tissue in Group A. Three cases in group A had collateral damage whereas in Group B, there were no added injuries. Post operative pain was studied only in cases undergoing adenoidectomy alone. Group A (n=8) demonstrated a pain score of 1.64-2.63-3.63 (95% CI) whereas Group B (n=11) demonstrated a pain score of 1.19-2.13-3.06 (95% CI). This difference was not statistically significant. In group A, the mean recovery period was 3.5 days and 2.93 days in Group B(p<0.05). CONCLUSION: Endoscopic powered adenoidectomy was found to be a safe and effective tool for adenoidectomy. The study parameters where endoscopic powered adenoidectomy fared better were completeness of resection, accurate resection under vision, lesser collateral damage and faster recovery time. On the other hand, conventional adenoidectomy scored in matter of lesser operative time and intra-operative bleeding. PMID- 27408283 TI - Anthropometric Parameters of Armed Forces Personnel. AB - BACKGROUND: The prevalence of obesity has increased globally in the last few decades. Anthropometry is an accepted method of measuring obesity. Charts of weight for height and age as well as Anthropometric indices like Body Mass Index (BMI) are commonly used to define normal, overweight and obese individuals. Weight for height charts currently in use in the Army belong to pre-independence era. It is widely believed that these have been obtained from life insurance tables made for British / American civilian population. The World Health Organization (WHO) encourages its member countries to develop their own reference anthropometric indices. METHODS: Anthropometric measurements were recorded for 902 healthy Armed Forces personnel in the age range of 28 to 52 years selected by stratified random sampling. These measurements were used to obtain mean values, standard deviations, medians and percentiles for various anthropometric parameters. RESULT: BMI for the study subjects ranged from 14.67 to 27.90 kg/m(2) with a mean of 20.52 Kg/m(2). No individual was categorized as obese using the current international cut-off of BMI >30 kg/m(2). With the exception of height, all other anthropometric parameters like weight, BMI, waist circumference, and waist-hip ratio were found to increase with increasing age. Correlation of BMI with waist circumference and BMI with Waist Hip Ratio in the study subjects was found to be statistically significant. The weight for height and age chart developed by this study shows an increase in weight in all age and height categories as compared to the weight for height chart currently in vogue in the Indian Army. CONCLUSION: The weight for height and age chart calculated in our study, shows considerable variation when compared to weight for height and age chart currently being used in Indian Army. The average weight for majority of height and age categories was found to be higher than in the Indian Army chart. It is recommended that a large multi-centric study should be taken up to gather more evidence to replace the current chart. PMID- 27408284 TI - Comparison of Crestal Bone Loss along Two Implant Crest Module Designs. AB - BACKGROUND: Crestal bone loss along the dental implant surface deranges its prognosis and is known to occur with implants having 02 mm smooth crest module/collar design. Implants with rough coated crest module/collar design are said to reduce crestal bone loss. Comparison of crestal bone loss with both crest module/collar designs of implants needs to be done. METHODS: Twenty cases were selected. Each case received one implant with smooth collar design (Group-A) and one implant with coated rough collar design (Group-B). All the 40 implants were prosthetically loaded after a healing period of six months. Crestal bone loss was measured on mesial, distal, buccal and lingual side of each implant using maxillofacial computed tomography at six, twelve and eighteen months time interval after placing the implants. Soft tissue evaluation was carried out around each implant using Gingival, Plaque and Calculus Indices, six and twelve months after loading the implants. RESULT: After 18 months i.e. one year after loading the implants, Group-A implants showed an overall average crestal bone loss of 1.53 mm and Group-B implants showed average bone loss of 1.42 mm, the difference being statistically significant (p < 0.05). For both types of implants, average crestal bone loss was maximum on the buccal side, followed by mesial, lingual and distal sides. Soft tissue evaluation revealed that the tissues remained healthy till the end of study for both types of implants. CONCLUSION: Crestal bone loss was less among implants with rough collar design as compared to smooth collar design. PMID- 27408285 TI - Role of Transpupillary Thermotherapy in Central Serous Chorio-Retinopathy. AB - BACKGROUND: To assess the efficacy of transpupillary thermo therapy (TTT) in cases of chronic central serous chorio- retinopathy (CSCR). METHODS: A prospective evaluation was carried out on 25 cases of chronic CSCR who were subjected to TTT. Resolution of CSCR and improvement in visual acuity was noted after six weeks of therapy. RESULT: Out of 25 patients, 13 (52%) had complete success (resolution of CSCR and improvement in visual acuity > 2 lines on Snellen's chart), 10 (42%) had qualified success (resolution of CSCR but no improvement in visual acuity) and two (8%) had failure to therapy (no resolution of CSCR or improvement in visual acuity). CONCLUSION: TTT maybe a good modality in aiding resolution of subretinal fluid in cases of chronic CSCR. However, improvement in visual function is dependent upon integrity of photo receptor layer of retina which is not influenced by this modality. A controlled study could be undertaken to compare outcome of TTT with conservative management in cases of early CSCR such that deleterious effects of chronic CSCR on the retinal photoreceptor layer are avoided. PMID- 27408286 TI - Profile of Culture Positive Enteric Fever from Bangalore. AB - BACKGROUND: Enteric fever is endemic in India. The aim of this study was to analyse the clinical, laboratory, antibiotic sensitivity profile and response to antibiotics of culture positive enteric fever patients from Bangalore. METHODS: In this retrospective study only culture positive enteric fever patients were taken and their clinical, laboratory, antibiotic sensitivity profile and the clinical response to antibiotics studied. RESULT: Eighty one culture positive enteric fever patients were taken into the study. Presenting symptoms included fever, pain abdomen (18.5%), loose stools (25%), vomiting (33%) and headache (30%). Absolute bradycardia at admission was not found in any of our patients. Normal or low total leucocyte count was seen in 97.5%. Typhoid hepatitis was seen in 8.5%. Salmonella enterica subspecies enterica serovar typhi (S typhi) were isolated in 80% of cases; 83% of all cases showed nalidixic acid resistance. All isolates were sensitive to chloramphenicol and third generation cephalosporins. Ciprofloxacin resistance was found in 19% cases. The time to defervescence in patients treated with ceftriaxone was 4.3 days. There was no statistical difference in time to defervescence in nalidixic acid resistant and sensitive strains. Complications included gastro intestinal bleed and encephalopathy. CONCLUSION: Prevalence of nalidixic acid resistance is high, while clinical resistance to quinolones may be higher than that found in the laboratory which requires detailed study. Chloramphenicol sensitivity has returned and nalidixic acid resistant and sensitive isolates are uniformly sensitive to third generation cephalosporins with no difference in time to defervescence. PMID- 27408287 TI - Prospective Study of Saline Infusion Sonography and Office Hysteroscopy. AB - BACKGROUND: To evaluate the diagnostic potential of saline infusion sonography to pick up uterine cavity lesions and compare it with the gold standard office hysteroscopy. METHODS: Study population consisted of women scheduled for office hysteroscopy for various indications. Uterine cavity of 208 women of the study group were evaluated first by saline infusion sonography and then by office hysteroscopy by two separate examiners. Findings were recorded separately for both procedures and compared. Pain rating was also noted after each procedure. RESULT: In eight patients either or both the procedures could not be performed for various reasons, hence were excluded from the analysis. With saline infusion sonography, pathological findings were identified in 93 (46.5%) patients and hysteroscopy detected lesions in 88 (44%) patients. For all findings combined sensitivity of saline infusion sonography was 90.9%, specificity 88.3%, positive predictive value 86.0% and negative predictive value 92.5% as compared to hysteroscopy. Former was less painful and easier to perform than the latter. CONCLUSION: The findings of saline infusion sonography and office hysteroscopy did not differ significantly. Thus saline infusion sonography is an excellent option for uterine cavity evaluation. PMID- 27408288 TI - Root Canal Treatment Using Thermoplasticized Carrier Condensation Technique. AB - BACKGROUND: The management of pulpally and apically infected teeth has evolved into a modality of conservation with predictable degree of success. Root canal treatment often requires protracted chairside time. A new technique involving placement of thermoplasticized core carrier obturators was compared with conventional lateral condensation technique. METHODS: A prospective, comparative, in-vivo cohort study was carried out on randomly selected 100 patients visiting a tertiary care centre from July 2005 to July 2007, for primary, non-surgical conservative management of teeth requiring root canal treatment. Two groups of fifty cases each were managed with lateral condensation and thermoplasticized core carrier obturation techniques. Outcome variables were rate of obturation and failure rates as assessed by clinical and radiological evaluation. RESULT: The time taken in case of lateral condensation of maxillary central incisor was 17.30 +/- 3.373 minutes and 28.07 +/- 2.586 minutes in case of mandibular molar. In the thermoplasticized carrier condensation technique, for the central incisors it took 13.00 +/- 1.376 minutes and 21.07 +/- 2.463 minutes for mandibular molars. The mean rank value for time taken for obturation as per Mann Whitney U test (p < 0.01) were 27.88 for maxillary incisor and 44.73 for mandibular molar in the lateral condensation technique and 13.13 and 16.27 respectively for thermoplasticized gutta percha carrier condensation. The values were statistically significant. With 16% and 14% cases having unsatisfactory filling as evaluated by post filling radiograph, Chi square test two tailed p value was 0.6836 and there was no statistically significant difference between the two groups. An absolute failure rate of 10% was seen in lateral condensation group and 6% in thermo-plasticized carrier condensation group. Fisher exact 2-tailed p value was 0.71 and the difference in failure rate was not statistically significant. CONCLUSION: Root canal obturation by thermoplasticized core carrier condensation technique is an effective alternative to conventional lateral condensation technique in terms of quick and successful outcome. PMID- 27408289 TI - Teledermatology in Air Force: Our Experience. AB - BACKGROUND: Teledermatology is the science of telemedicine applied to the field of dermatology, with an aim to avoid travelling to nearest specialist facility. METHODS: Patients from Air Force Stations Jaisalmer, Naliya, 5 Air Force Hospital, Jorhat and 9 Air Force Hospital, Halwara were consulted by the dermatologist at Command Hospital (Air Force) Bangalore through the telemedicine network provided by ISRO, Bangalore from March 06 to May 08. RESULT: 115 patients underwent teledermatology consultation using virtual teleconference (VTC) and this was compared with Store and Forward (S and F) consultation at all four stations as well as Face to Face (FTF) consultation at 5 Air Force Hospital Jorhat. Diagnosis concordance was 52.5% and 53% for Jorhat and Halwara for VTC vs S and F, while it was 75% and 25% for Jaisalmer and Naliya. For VTC vs FTF, the concordance improved to 60.66% and for S and F vs FTF it improved to 91.8%. Concordance was better for localized lesions than for generalized lesions especially of the papulosquamous group of disorders. Another reason for the discordance with VTC was poor resolution of cameras at the peripheral units. CONCLUSION: Teledermatology is useful for patient care in the absence of local specialist cover and the patients have to travel long distances resulting in loss of manhours. However, better camera resolution at peripheral centres will result in greater concordance. PMID- 27408290 TI - Visual Prosthesis: Artificial Vision. PMID- 27408291 TI - Clinical Applications of PET and PET-CT. AB - Positron emission tomography (PET) and PET/ computed tomography (CT) are emerging as important imaging techniques and their popularity is growing within the medical fraternity. Though PET has been a useful research tool for many decades its real growth into clinical applications has occurred in the last one decade or so. Currently its major use is in oncologic imaging. However it has a multitude of clinical applications in cardiology, neurology and psychiatry as well. In oncologic imaging, a major advantage of PET is that a single whole-body examination can provide accurate assessment of disease activity and spread. PET/CT amalgamates the functional information of PET with the structural details of the CT scan, thus greatly aiding in accurate staging, therapy response assessment and early detection of recurrent disease. PMID- 27408292 TI - Bioshock: Biotechnology and Bioterrorism. AB - In the recent past, the threat of a global bioterrorist attack has increased dramatically. In addition to the already existing microorganisms and techniques, the recent explosion in biotechnology has considerably added to the arsenal of the bioterrorist. Molecular technologies are now available which can be used by committed bioterrorist groups to manipulate and modify microorganisms so as to make them increasingly infectious, virulent or treatment resistant for causing maximum casualties. Infectious diseases which are likely to be used as bioweapons are Anthrax, Botulism, Plague, Smallpox and Brucella. Molecular techniques like immunoassays and nucleic acid amplification are now available to detect bioattacks. This article discusses the threat of bioterrorism. It also evaluates the molecular diagnostic methods and the future of early containment of a bioterrorist attack using molecular techniques. PMID- 27408293 TI - The First Successful Pediatric Liver Transplant in the Armed Forces. PMID- 27408294 TI - Scalp Metastases from Thyroid Carcinoma. PMID- 27408295 TI - Two Cases of Penetrating Injury of the Neck. PMID- 27408296 TI - Spontaneous Separation of Classical Uterine Scar. PMID- 27408297 TI - Richter's Syndrome. PMID- 27408298 TI - Large Bowel Obstruction by Anomalous Congenital Band. PMID- 27408299 TI - Acute Renal Failure with Hyperkalemia Presenting as Recurrent Syncope. PMID- 27408300 TI - GERD: 'silent refluxers'. PMID- 27408301 TI - Incidence of Hepatitis E Virus Infection in Recipients of Blood or Blood Products Transfusion. AB - BACKGROUND: Hepatitis E, generally known to be transmitted faeco-orally, has been shown to have significant transmission by blood borne route. Paucity of data on asymptomatic viremia in blood donors and higher incidence of Hepatitis E in haemodialysis patients and thalassemics mandate a prospective study of blood recipients to elucidate the exact incidence and natural history of post transfusion Hepatitis E. METHODS: A total of 2000 recipients of blood or blood products transfusion were followed up for two months to detect development of post transfusion Hepatitis E, by clinical examination, transaminases and immunoglobulin M anti hepatitis E virus (IgM anti HEV). Estimation of hepatitis E virus ribonucleic acid (HEV RNA) was done in patients with elevated levels of transaminases. RESULT: Out of 2000 patients, 5(0.25%) were positive for IgM anti HEV at the time of transfusion and were excluded from the study. Rest of 1995 patients were followed up for two months post transfusion. A total of 1303 (65.3%) patients were followed up for two months and 1636 (82.0%) patients at least once in two visits. None of the followed up patients reported development of jaundice or had clinically evident hepatitis, although 62 patients had raised transaminases detected at either one or both the visits. CONCLUSION: All followed up patients were tested for IgM anti HEV at both the visits and none were found to be positive. Patients with raised transaminases were subjected to HEV RNA and all were found to be negative. PMID- 27408302 TI - Toxicity of Low-Dose Intermittent Isotretinoin in Recalcitrant Acne. AB - BACKGROUND: Isotretinoin, an oral retinoid, has been utilized to achieve long term remissions in cases of recalcitrant acne. In the conventional dosage schedule, the use of oral isotretinoin has been limited by the occurrence of biochemical abnormalities such as hypertriglyceridaemia and impaired liver function tests and radiological changes consistent with diffuse idiopathic skeletal hyperostosis. Low-dose intermittent regimen of oral isotretinoin has been evolved as a cost effective alternative to the conventional dosage regimen in cases of acne. This study addresses the issue of adverse effects of low-dose intermittent isotretinoin and the safety of this regimen. METHODS: A total of 60 cases of recalcitrant acne were included in the study. Baseline haematological, biochemical and radiological investigations were carried out. Low-dose intermittent isotretinoin was instituted in a dose of 0.5 mg/kg/day for one week in every four weeks for six months. The investigations were repeated at the end of six months therapy. RESULT: High triglyceride levels occurred in 5% of cases whereas impaired liver function tests and skeletal hyperostosis of the spine were not observed in any case after low-dose intermittent isotretinoin. CONCLUSION: The low-dose intermittent regimen in cases of acne may be utilized to limit the systemic toxicity of oral isotretinoin. PMID- 27408303 TI - Treatment of Endometriosis and Chronic Pelvic Pain with Letrozole and Norethindrone Acetate. AB - BACKGROUND: Endometriosis is encountered in 7-10% of actively menstruating women, with a suspected prevalence as high as 22% in asymptomatic women. It is an important cause of chronic pelvic pain. The aim of this study was to evaluate the efficacy and safety of letrozole in combination with norethindrone acetate and calcium in the management of endometriosis associated pelvic pain. METHODS: Prospective non-randomized open label study was carried out including 20 patients with endometriosis related pelvic pain that was refractory to previous treatments. RESULT: In all 14 patients completed the study. All patients showed significant improvement of pain scores and revealed significant improvement of features of endometriosis on being given letrozole in combination with norethindrone acetate and calcium. CONCLUSION: Letrozole is an effective drug for treatment of endometriosis. PMID- 27408304 TI - Clinicopathological Spectrum of Renal Biopsies in Children. AB - BACKGROUND: Renal biopsy has revolutionized the study of glomerular diseases. A retrospective analysis of 104 consecutive renal biopsies performed in children at a tertiary care referral centre over five years is presented. METHODS: All the biopsies were performed non-ultrasound guided by a single consultant nephrologist. Trucut needles were used in the initial few years and a Magnum biopsy gun (Bard) over subsequent three years. There were 66 boys and 38 girls. RESULT: A male predominance occurred in the older and younger patients. The male: female ratio was 2.2:1, 1:1, and 2.7:1 for the age groups below five years, 5-10 years and above 10 years respectively. All patients tolerated the biopsy well and success rate was 94%. There were minimal complications in the form of post biopsy haematuria (33.3%). Haematuria was mild in most of the cases and settled down within 24 hours. None required transfusion. However, 60% patients had mild discomfort in the form of local pain. There was no mortality, infection or renal loss. The most common indication for a kidney biopsy was nephrotic syndrome. Out of 104 biopsies, 85 were in children with nephrotic syndrome. The commonest primary renal pathology was mesangial proliferative glomerulonephritis (38%), minimal change disease (19%), focal segmental glomerulosclerosis (15%) and membranoproliferative glomerulonephritis (7%). CONCLUSION: Renal biopsy is a safe procedure in experienced hands and the commonest indication for a biopsy in children remains nephrotic syndrome. PMID- 27408305 TI - Efficacy of Second Molar to Achieve Anchorage Control in Maximum Anchorage Cases. AB - BACKGROUND: The aim of the study was to assess the efficacy of inclusion of second molar in treatment at the outset to reinforce anchorage. METHODS: A comparative study comprising of 30 maximum anchorage cases to quantify anchorage loss in two situations was undertaken. Group I consisted of cases in which only first molars were banded and Group II consisted of cases where both first and second molars were banded. A total of seven landmarks were marked and six measurements were recorded on to the pre-treatment and post-treatment lateral cephalogram. RESULT: The difference in pre-treatment and post-treatment values of all the variables were statistically significant (p<0.05) except maxillary central incisor vertical movement (U1 VER), implying a significant post-treatment change. Thus in both the treatment approaches U6 and U1 showed a considerable amount of movement in horizontal and vertical direction and there was rotation which brought about change in angular values. CONCLUSION: The study has successfully quantified the anchorage loss and brought out the advantages of including second molar in treatment at the outset. Not only the anchorage loss is minimized but inclusion of second molar also helps to maximize incisor retraction and helps control angular movement of molar and incisor. Extra time required for second molar banding is well spent, as the benefits are overwhelming. PMID- 27408306 TI - Atypical Squamous Cells of Undetermined Significance : A Follow up Study. AB - BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) is the term in cervical cytology reporting where the changes are suggestive of a sqamous extraepithelial lesion but lack criteria for definition interpretation. Its clinical significance is variable. METHODS: A one year study in a zonal hospital evaluating all cervical smears received for cytology by two pathologists independently and subsequently reported as per the Bethesda guidelines. The patients were folloed up for six months. RESULT: A total of 24 (4%) smears were reported as ASCUS out of 604 examined. Of these, 15 were followed up for one year. Mean age was 39 years and 60% were premenopausal. After six months, 11 cases were reported negative for intraepithelial lesion or malignancy and four showed ASCUS on repeat pap smear. CONCLUSION: ASCUS shows a repression rate of 73%. Colpscopic evaluation should be done only if ASCUS persists. Diligent follow up and biopsy, when indicated is a must. PMID- 27408307 TI - Role of Prophylactic Antibiotics in Laparoscopic Cholecystectomy. AB - BACKGROUND: Antibiotic prophylaxis is routinely administered in laparoscopic cholecystetomy but its role is debatable. METHODS: From January 2004 to August 2008, 417 patients were randomized into 208 in antibiotic group (AG) and 209 in non antibiotic group (NAG). AG received one dose each of injection ciprofloxacin (200 mg) and metronidazole (500mg) preoperatively. NAG was given only intravenous fluids. Besides routine care, all underwent abdominal sonography and liver function tests at least once during the 30 postoperative days. RESULT: Age, sex and co-morbidity distribution were similar in both the groups. One patient who was on weekly 5mg methotraxate (NAG) had erythema around umbilical port. Other three having umbilical discharge recovered without antibiotics. Nine patients had subhepatic collection (5 AG and 4 NAG). One from NAG underwent re-laparoscopy and drainage. Ten patients had fever. Two from AG had basal lung collapse and were given antibiotics. CONCLUSION: Antibiotic prophylaxis is not needed for laparoscopic cholecystectomy. PMID- 27408308 TI - Determination of Working Length of Root Canal. AB - BACKGROUND: This study was undertaken to determine the working length of root canal by microprocessor controlled impedance quotient apex locator and conventional radiographic method. METHODS: Patients whose teeth were to be extracted were selected for this study. A total of 100 teeth in the same or different patients were identified. Biomechanical preparation of the canal was done for smooth negotiation of the entire canal. The electrode of the Root ZXTM was attached to the selected file and the length adjusted till the beep of the Root ZXTM indicated the apical foramen. The electrode was removed but the file was stabilized with the help of soft gutta percha. An intraoral periapical (IOPA) radiograph was taken using basic guidelines. The tooth was then extracted under local anaesthesia along with the file in the tooth. A window was cut on one surface of the root apex approximately 4mm from the apex to expose the root canal. The file tip was identified. The distance of the file tip from the apex was measured under 3X magnification and the reading recorded. Similarly the distance from the file tip to the radiographic apex was measured on the radiograph under magnification and the reading recorded. All the readings were tabulated. The actual distances measured between the extracted tooth, the electronic apex locator and on the radiograph were compared using a paired 't' test to determine the accuracy of each method in relation to the minor diameter. RESULT: It was observed that the radiographic method had a significant variation from the electronic method when compared to the actual measurement on the extracted tooth. CONCLUSION: The electronic method is a more accurate method as compared to radiographic method for determination of working length of the root canal. PMID- 27408309 TI - Ocular Lesions Associated with Human Immunodeficiency Virus Infection. AB - INTRODUCTION: This study was undertaken to document the various ocular manifestations in human immunodeficiency virus (HIV) infected individuals and to correlate such findings with CD4+ T lymphocyte levels in individuals with ocular manifestations. METHODS: A total of 150 patients known to be HIV positive referred to a tertiary level army hospital were included in this cross sectional study. All patients underwent complete ophthalmic evaluation. CD4+ count was done only in patients in whom ocular lesions were noted. RESULT: Most patients (54.66%) were in the 31-40 years age group. Majority of patients (84.66%) were males. Infection was sexually acquired in 91.33% by heterosexual mode. Majority of cases (34%) examined had presented within 12-18 months of being detected positive for HIV. Ocular involvement was present in 76 (50.66%) cases and the commonest ocular lesion encountered was cytomegalovirus (CMV) retinitis in 23 (30.26%) cases. CD4+ count less than 50 cells/ul was consistently associated with ocular manifestations in 36.84% of HIV positive patients. CONCLUSION: This study showed the whole spectrum of ocular lesions in HIV positive cases from CMV retinitis to adnexal lesions. No case of ocular Kaposi's sarcoma was seen in this study. PMID- 27408310 TI - Esthetics and Biocompatibility of Composite Dental Laminates. AB - BACKGROUND: Advances in modern dental materials provide patients with a choice of natural looking veneers to provide esthetic restorations. These may be directly fabricated composite resin veneers or indirectly fabricated veneers. This study was carried out to evaluate the clinical effect of new generation indirect veneering composites and to compare them with veneers fabricated from direct composite restorations. METHODS: The present study was carried out in the Prosthodontics department of a medical college. A total of forty patients requiring restoration of the anterior teeth using composite veneers were selected and either of the two materials was used to fabricate the veneers. RESULT: Clinical evaluation was done for esthetics and periodontal health. Statistical analysis showed that there were no significant changes to the periodontal health during the period of the study. CONCLUSION: The evidence obtained from this study indicates that both direct as well as indirect composite materials had clinically acceptable outcomes in terms of restoration of esthetics. Biocompatibility with the periodontal tissues of both materials was also evident by the improvement in oral health indices used in the study. PMID- 27408311 TI - Laryngopharyngeal Reflux : Larynx on Fire. AB - Laryngopharyngeal Reflux (LPR) is a commonly occurring and recently described clinical entity due to the retrograde flow of gastric contents into the pharynx. It accounts for many symptoms of upper airway including hoarseness, chronic throat irritation and globus sensation. The sensitive laryngeal mucosa is prone to damage by the combination of acid and pepsin. The inflammatory changes that follow are presumed to cause the symptoms and predispose the individual to laryngeal disorders. Diagnosis can usually be made clinically based on symptoms and laryngeal signs but a 24 hour pH metry is essential to establish diagnosis. Treatment centres on lifestyle modifications, vocal hygiene measures and long term use of proton pump inhibitors. Recent research in this field may lead to a better understanding of the pathophysiology of the disease and change the way LPR is managed. PMID- 27408312 TI - Prevalent and Emerging Therapies for Osteoporosis. AB - Osteoporosis and fractures associated with it constitute a real and serious socio medical problem, which only recently has come to the forefront of social consciousness. With increasing number of exservicemen and their dependents, osteoporosis management has become very important in our setup. Currently available pharmacological therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Oral bisphosphonates are the standard treatment for osteoporosis which are associated with significant gastrointestinal side effects and thus poor patient compliance. Newer regimens, including intravenous (IV) formulations of bisphosphonates, have successfully come in vogue with greater patient compliance and equal or better benefits. The real need in osteoporosis treatment is for additional anabolic drugs. The only currently approved anabolic agent for treating osteoporosis is teriparatide (recombinant human parathyroid hormone 1-34), which stimulates new bone formation. Considerable efforts are being made to develop new, more effective treatment for osteoporosis. These novel drugs under trial include those primarily inhibiting osteoclastic bone resorption (like bisphosphonates) such as inhibitors of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling, cathepsin K inhibitors, c-Src kinase inhibitors, integrin inhibitors, chloride channel inhibitors and the drugs with osteo-anabolic actions such as orally active parathyroid hormone (PTH) analogues, calcium sensing receptor antagonists, PTH-related peptide analogues and agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling; sclerostin antibodies). PMID- 27408313 TI - Bioterrorism : A Public Health Perspective. AB - The intentional release or threat of release of biologic agents (i.e. viruses, bacteria, fungi or their toxins) in order to cause disease or death among human population or food crops and livestock to terrorize a civilian population or manipulate the government in the present scenario of increased terrorist activity has become a real possibility. The most important step in the event of a bioterrorist attack is the identification of the event. This can be achieved by generating awareness, having high degree of suspicion and having a good surveillance system to assist quick detection. Bioterrorist attacks could be covert or announced and caused by virtually any pathogenic microorganism. Bioterrorist agents of major concern have been categorized as A, B and C based on the priority of the agents to pose a risk to the national security and the ease with which they can be disseminated. The five phases of activities in dealing with a bioterrorist attack are preparedness phase, early warning phase, notification phase, response phase and recovery phase. A bioterrorism attack in a public place is a public health emergency. Early detection and rapid investigation is the key to contain such attacks. The role of public health epidemiologist is critical not only in determining the scope and magnitude of the attack but also in effective implementation of interventions. PMID- 27408314 TI - Determinants of Acclimatisation in High Altitude. AB - BACKGROUND: A total of 31 cases of effects of high altitude were admitted to a field hospital from a particular sector during the year 2008. This study was hence undertaken to see the efficacy of acclimatisation as well as outline the determinants of acclimatisation. METHODS: The study monitored the transients in the acclimatisation period as well as laid down the guidelines to certify their fitness after the acclimatisation period. RESULT: Almost 4.70% of transients were found unfit to proceed to higher altitudes even after acclimatisation. Tachycardia with oxygen saturation below 90% by digital pulse oximetry were the parameters found to be statistically significant as an indicator to declare a person as not fully acclimatised or otherwise. CONCLUSION: The administrative authorities must ensure that an individual is fully acclimatized, based on the fitness certificates issued, before being dispatched to their units located in high altitude areas. PMID- 27408315 TI - A Case of Intravaginal Foreign Body. PMID- 27408316 TI - Functional Adrenocortical Tumour in Young. PMID- 27408317 TI - Pseudoxanthoma Elasticum with Renal Cortical Calcification. PMID- 27408318 TI - Pancreatic Metastases from Renal Cell Carcinoma Presenting as Intestinal Obstruction. PMID- 27408319 TI - Chicken Pox with Multisystem Complications. PMID- 27408320 TI - Ballantyne Syndrome in Rhesus Isoimmunised Pregnancy. PMID- 27408321 TI - Functional Jaw Orthopaedics for Management of Class II Division 1 Malocclusion. PMID- 27408322 TI - ERRATUM. AB - [This corrects the article DOI: 10.1016/S0377-1237(10)80153-4.]. PMID- 27408323 TI - Neurotoxic Effects of Topical Cyclopentolate. PMID- 27408324 TI - Reversible Bleomycin Toxicity. PMID- 27408325 TI - Granular Cell Tumour of Breast : A Mimic of Carcinoma. PMID- 27408326 TI - Missed Diagnosis of Multiple Endocrine Neoplasia Type 2 B. PMID- 27408327 TI - A Case of Katayama Fever (Acute Schistosomiasis). PMID- 27408328 TI - Isolated Diastematomyelia - A Rare but Crucial Antenatal Diagnosis. PMID- 27408329 TI - Detection of Mycobacterium avium subspecies paratuberculosis in tie-stall dairy herds using a standardized environmental sampling technique and targeted pooled samples. AB - Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of Johne's disease, a chronic contagious enteritis of ruminants that causes major economic losses. Several studies, most involving large free-stall herds, have found environmental sampling to be a suitable method for detecting MAP-infected herds. In eastern Canada, where small tie-stall herds are predominant, certain conditions and management practices may influence the survival and transmission of MAP and recovery (isolation). Our objective was to estimate the performance of a standardized environmental and targeted pooled sampling technique for the detection of MAP-infected tie-stall dairy herds. Twenty-four farms (19 MAP infected and 5 non-infected) were enrolled, but only 20 were visited twice in the same year, to collect 7 environmental samples and 2 pooled samples (sick cows and cows with poor body condition). Concurrent individual sampling of all adult cows in the herds was also carried out. Isolation of MAP was achieved using the MGIT Para TB culture media and the BACTEC 960 detection system. Overall, MAP was isolated in 7% of the environmental cultures. The sensitivity of the environmental culture was 44% [95% confidence interval (CI): 20% to 70%] when combining results from 2 different herd visits and 32% (95% CI: 13% to 57%) when results from only 1 random herd visit were used. The best sampling strategy was to combine samples from the manure pit, gutter, sick cows, and cows with poor body condition. The standardized environmental sampling technique and the targeted pooled samples presented in this study is an alternative sampling strategy to costly individual cultures for detecting MAP-infected tie-stall dairies. Repeated samplings may improve the detection of MAP-infected herds. PMID- 27408330 TI - Association between thermal environment and Salmonella in fecal samples from dairy cattle in midwestern United States. AB - The objective of this study was to describe the association between thermal measures in the barn environment (pen temperature and humidity) and fecal shedding of Salmonella in dairy cattle. A repeated cross-sectional study was conducted within a commercial dairy herd located in the midwestern United States. Five pooled fecal samples were collected monthly from each pen for 9 mo and submitted for microbiological culture. Negative binomial regression methods were used to test the association [incidence rate ratio (IRR)] between Salmonella pen status (the count of Salmonella-positive pools) and thermal environmental parameters [average temperature and temperature humidity index (THI)] for 3 time periods (48 h, 72 h, and 1 wk) before fecal sampling. Salmonella was cultured from 10.8% [39/360; 95% confidence interval (CI): 7.8% to 14.5%] of pooled samples. The highest proportion of positive pools occurred in August. The IRR ranged from 1.26 (95% CI: 1.15 to 1.39, THI 1 wk) to 4.5 (95% CI: 2.13 to 9.51, heat exposure 1 wk) across all thermal parameters and lag time periods measured. For example, the incidence rate of Salmonella-positive pools increased by 54% for every 5 degrees C increment in average temperature (IRR = 1.54; 95% CI: 1.29 to 1.85) and 29% for every 5-unit increase in THI (IRR = 1.29; 95% CI: 1.16 to 1.42) during the 72 h before sampling. The incidence rate ratio for pens exposed to higher temperatures (> 25 degrees C) was 4.5 times (95% CI: 2.13 to 9.51) the incidence rate ratio for pens exposed to temperatures < 25 degrees C in the 72 h before sampling. Likewise, the incidence rate ratio for pens exposed to THI > 70 was 4.23 times greater (95% CI: 2.1 to 8.28) than when the THI was < 70 in the 72 h before sampling. An association was found between the thermal environment and Salmonella shedding in dairy cattle. Further research is warranted in order to fully understand the component risks associated with the summer season and increased Salmonella shedding. PMID- 27408331 TI - Reinfection of adult cattle with rotavirus B during repeated outbreaks of epidemic diarrhea. AB - Rotavirus B (RVB) infection in cattle is poorly understood. The objective of this study was to describe the epidemiological features of repeated outbreaks of epidemic diarrhea due to RVB infection in adult cattle on a large dairy farm complex in Japan. In October 2002, approximately 550 adult cows and approximately 450 in February 2005 had acute watery diarrhea at several farms on the complex. Four months before the first outbreak, RVB antibody-positive rates at subsequently affected farms were significantly lower than at non-affected farms (30% to 32% versus 61% to 67%). During the acute phase of both outbreaks, RVB antibody-positive rates in diarrheal cows tested were as low as 15% to 26%. Most of the farms affected in the second outbreak were also involved in the first outbreak. Some adult cows with RVB diarrhea in the first outbreak showed not only RVB seroresponse, but also RVB shedding in the second outbreak, although none of these cows developed diarrhea. Nucleotide sequences of the VP7 and VP4 genes revealed a close relationship between RVB strains in both outbreaks. Taken together, these results indicate that outbreaks of epidemic RVB diarrhea in adult cows might be influenced by herd immunity and could occur repeatedly at the same farms over several years. To our knowledge, this is the first report on repeated RVB infections in the same cattle. PMID- 27408332 TI - Validation of an assay for quantification of alpha-amylase in saliva of sheep. AB - The objective of this study was to develop a time-resolved immunofluorometric assay (TR-IFMA) for quantification of salivary alpha-amylase in sheep. For that purpose, after the design of the assay, an analytical and a clinical validation were carried out. The analytical validation of the assay showed intra- and inter assay coefficients of variation (CVs) of 6.1% and 10.57%, respectively and an analytical limit of detection of 0.09 ng/mL. The assay also demonstrated a high level of accuracy, as determined by linearity under dilution. For clinical validation, a model of acute stress testing was conducted to determine whether expected significant changes in alpha-amylase were picked up in the newly developed assay. In that model, 11 sheep were immobilized and confronted with a sheepdog to induce stress. Saliva samples were obtained before stress induction and 15, 30, and 60 min afterwards. Salivary cortisol was measured as a reference of stress level. The results of TR-IFMA showed a significant increase (P < 0.01) in the concentration of alpha-amylase in saliva after stress induction. The assay developed in this study could be used to measure salivary alpha-amylase in the saliva of sheep and this enzyme could be a possible noninvasive biomarker of stress in sheep. PMID- 27408333 TI - Effects of the -791(C->T) mutation in the promoter for tumor necrosis factor alpha on gene expression and resistance of Large White pigs to enterotoxigenic Escherichia coli F18. AB - Tumor necrosis factor alpha (TNF-alpha) plays an important role in the immune system. In this study, TNF-alpha expression was analyzed in 11 tissues of 8 piglets resistant to enterotoxigenic Escherichia coli (ETEC) F18 and 8 ETEC F18 susceptible piglets from the Large White breed. The expression levels of TNF alpha were high in immune organs (spleen, lung, thymus, and lymph nodes). The levels were higher in ETEC F18-resistant piglets than in ETEC F18-susceptible piglets, with significant differences in spleen, kidney, thymus, lymph node, and duodenum (P < 0.05). The mutation TNF-alpha -791(C->T) and 3 genotypes (CC, CT, and TT) were identified. The TNF-alpha expression levels in the spleen, kidney, lymph nodes, and duodenum were significantly higher in the TT pigs than in the CC pigs (P < 0.05). Thus, TNF-alpha -791(C->T) has significant effects on mRNA expression and may regulate ETEC F18 resistance of weaning piglets. Therefore, the -791(C->T) mutation of the TNF-alpha gene could be considered an important potential genetic marker of ETEC F18 resistance. PMID- 27408334 TI - Effects of inhibitors of vascular endothelial growth factor receptor 2 and downstream pathways of receptor tyrosine kinases involving phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin or mitogen-activated protein kinase in canine hemangiosarcoma cell lines. AB - Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm with no current effective treatment. Previous studies showed that receptor tyrosine kinases and molecules within their downstream pathways involving phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (m-TOR) or mitogen-activated protein kinase (MAPK) were overexpressed in canine, human, and murine tumors, including HSA. The present study investigated the effects of inhibitors of these pathways in canine splenic and hepatic HSA cell lines using assays of cell viability and apoptosis. Inhibitors of the MAPK pathway did not affect canine HSA cell viability. However, cell viability was significantly reduced by exposure to inhibitors of vascular endothelial growth factor receptor 2 and the PI3K/Akt/m TOR pathway; these inhibitors also induced apoptosis in these cell lines. These results suggest that these inhibitors reduce the proliferation of canine HSA cells by inducing apoptosis. Further study of these inhibitors, using xenograft mouse models of canine HSA, are warranted to explore their potential for clinical application. PMID- 27408335 TI - Relationship of skeletal muscle inflammation with obesity and obesity-associated hyperinsulinemia in horses. AB - Local (skeletal muscle and adipose) and systemic inflammation are implicated in the development of obesity-associated insulin resistance in humans. In horses, obesity is neither strongly nor consistently associated with systemic inflammation. The role of skeletal muscle inflammation in the development of insulin dysregulation (insulin resistance or hyperinsulinemia) remains to be determined. We hypothesized that skeletal muscle inflammation is related to obesity-associated hyperinsulinemia in horses. Thirty-five light-breed horses with body condition scores (BCSs) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS >= 7, resting serum insulin < 30 MUIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin >= 30 MUIU/mL) horses. Inflammatory biomarkers were evaluated in skeletal muscle biopsies and plasma. Relationships between markers of inflammation and BCS were evaluated. To assess the role of inflammation in obesity-associated hyperinsulinemia, markers of inflammation were compared among lean or ideal, normoinsulinemic (L-NI); obese, normoinsulinemic (O NI); and obese, hyperinsulinemic (O-HI) horses. Skeletal muscle and plasma tumor necrosis factor alpha (TNFalpha) concentrations were negatively correlated with BCS. When comparing inflammatory markers among groups, skeletal muscle TNFalpha was lower in the O-HI group than in the O-NI or L-NI groups. In horses, neither skeletal muscle nor systemic inflammation appears to be positively related to obesity or obesity-associated hyperinsulinemia. PMID- 27408336 TI - A new technique for repeated biopsies of the mammary gland in dairy cows allotted to Latin-square design studies. AB - The objective of this study was to develop a technique for carrying out repeated biopsies of the mammary gland of lactating dairy cows that provides enough material to monitor enzyme activities and gene expression in mammary secretory tissue. A total of 16 Holstein cows were subjected to 4 mammary biopsies each at 3-week intervals for a total of 64 biopsies. A 0.75-cm incision was made through the skin and subcutaneous tissue of the mammary gland and a trocar and cannula were inserted using a circular motion. The trocar was withdrawn and a syringe was plugged into the base of the cannula to create a vacuum for sampling mammary tissue. To reduce bleeding, hand pressure was put on the surgery site after biopsy and skin closure and ice was applied for at least 2 h after the biopsy using a cow bra. The entire procedure took an average of 25 min. Two attempts were usually enough to obtain 800 mg of tissue. Visual examination of milk samples 10 d after the biopsy indicated no trace of blood, except in samples from 2 cows. All wounds healed without infection and subcutaneous hematomas resorbed within 7 d. There was no incidence of mastitis throughout the lactation. This technique provides a new tool for biopsy of the mammary gland repeated at short intervals with the main effect being a decrease in milk production. Although secondary complications leading to illness or death are always a risk with any procedure, this biopsy technique was carried out without complications to the health of animals and with no incidence of mastitis during the lactation. PMID- 27408337 TI - Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses. AB - The aim of this study was to determine the pharmacokinetics of amikacin and penicillin G sodium when administered in combination as an intravenous regional limb perfusion (IVRLP) to horses. Seven healthy adult horses underwent an IVRLP in the cephalic vein with 2 g of amikacin sulfate and 10 mill IU of penicillin G sodium diluted to 60 mL in 0.9% saline. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min. Synovial fluid was collected from the metacarpophalangeal joint 35 min and 2, 6, 12, and 24 h after infusion of the antimicrobials. Concentrations of amikacin and penicillin in synovial fluid were quantitated by liquid chromatography tandem-mass spectrometry analysis. Therapeutic concentrations of amikacin and penicillin for equine-susceptible pathogens were achieved in the synovial fluid. Maximum synovial concentrations (Cmax) (mean +/- SE) for amikacin and penicillin were 132 +/- 33 MUg/mL and 8474 +/- 5710 ng/mL, respectively. Only 3 horses had detectable levels of penicillin at 6 h and 1 at the 12 h sample. The combination of amikacin with penicillin G sodium via IVDLP resulted in reported therapeutic concentrations of both antibiotics in the synovial fluid. The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1 and Time > MIC for penicillin was 6 h. At 24 h, the mean concentration of amikacin was still above 4 MUg/mL. Terminal elimination rate constants (T1/2 lambdaz) were 13.6 h and 2.8 h for amikacin and penicillin, respectively. The use of IVDLP with penicillin may therefore not be practical as rapid clearance of penicillin from the synovial fluid requires frequent perfusions to maintain acceptable therapeutic concentrations. PMID- 27408338 TI - Changes in gene expression of tumor necrosis factor alpha and interleukin 6 in a canine model of caerulein-induced pancreatitis. AB - Acute pancreatitis is an inflammatory process that frequently involves peripancreatic tissues and remote organ systems. It has high morbidity and mortality rates in both human and veterinary patients. The severity of pancreatitis is generally determined by events that occur after acinar cell injury in the pancreas, resulting in elevated levels of various proinflammatory mediators, such as interleukin (IL) 1beta and 6, as well as tumor necrosis factor alpha (TNF-alpha). When these mediators are excessively released into the systemic circulation, severe pancreatitis occurs with systemic complications. This pathophysiological process is similar to that of sepsis; thus, there are many striking clinical similarities between patients with septic shock and those with severe acute pancreatitis. We induced acute pancreatitis using caerulein in dogs and measured the change in the gene expression of proinflammatory cytokines. The levels of TNF-alpha and IL-6 mRNA peaked at 3 h, at twice the baseline levels, and the serum concentrations of amylase and lipase also increased. Histopathological examination revealed severe hyperemia of the pancreas and hyperemia in the duodenal villi and the hepatic sinusoid. Thus, pancreatitis can be considered an appropriate model to better understand the development of naturally occurring sepsis and to assist in the effective treatment and management of septic patients. PMID- 27408339 TI - Prevalence of netF-positive Clostridium perfringens in foals in southwestern Ontario. AB - NetF-producing Clostridium perfringens have recently been identified as a cause of necrotizing enteritis in neonatal foals, but little is known about its prevalence in clinically normal foals. Foals (n = 88) ranging in age from < 1 wk to 2 to 4 mo (median age 2 to 4 wk) on 8 horse-breeding farms in Ontario were examined on 1 or 2 occasions for the presence of C. perfringens. Of the foals that tested positive, 5 isolates (n = 675) were examined for the netF and enterotoxin (cpe) genes. Colonization by C. perfringens was most marked in foals < 1 wk of age [4.85 +/- 2.70 log10 colony-forming units (CFU)] and declined markedly over time (1.23 +/- 1.06 log10 CFU at 1 to 2 mo of age). Only 2 isolates possessed the cpe gene and none possessed netF. We concluded that netF-positive C. perfringens does not colonize young foals with any detectable frequency in Ontario and this organism is not likely to be adapted to the intestine of the horse. PMID- 27408340 TI - Protective efficacy by various doses of Salmonella ghost vaccine candidate carrying enterotoxigenic Escherichia coli fimbrial antigen against neonatal piglet colibacillosis. AB - Humoral immune responses and protective efficacy by various doses of Salmonella ghost cells carrying enterotoxigenic Escherichia coli (ETEC) fimbrial antigens for protection against piglet colibacillosis were studied. All groups were orally primed and boosted at 11 and 14 wk of pregnancy, respectively. Group A sows were inoculated with phosphate-buffered saline (PBS), and groups B, C, and D sows were immunized with 2 * 10(9), 2 * 10(10), and 2 * 10(11) ghost cells, respectively. Serum immunoglobulin (Ig) G, and colostrum IgG and IgA levels of groups C and D sows were significantly higher than those of group A sows. In addition, serum IgG and IgA levels in group C and D piglets were significantly increased compared to those of group A piglets. After challenge with wild-type ETEC, diarrhea and mortality were not observed in group C and D piglets, while diarrhea was observed in 88.9% and 58.8% of groups A and B piglets, respectively, and 16.7% mortality was observed in group A piglets. These findings indicate that oral immunization of sows with 2 * 10(10) or 10(11) ghost cells can effectively protect their offspring from colibacillosis. PMID- 27408341 TI - Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep. AB - The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep. PMID- 27408342 TI - CD5 Positive B Lymphoblastic Leukemia: Report of a Case with Review of Literature. AB - We report a rare CD5 positive B cell acute lymphoblastic leukemia (B-ALL) with a review of the clinopathological features and prognosis of previously reported cases in the literature. The aberrant expression of CD 5 antigen is uncommon in B ALL; the morphological differential diagnosis includes blastic mantle cell lymphoma, denovo CD5(+) diffuse large B cell lymphoma and secondary diffuse large cell lymphoma/Richter's transformation. CD5(+) B cell ALL is commonly reported in younger patients (<18 years). Though the expression of T cell antigens is reported to have poor prognosis, the experience with CD5(+) B-ALL is limited to draw any firm conclusion regarding its prognosis. PMID- 27408343 TI - Fanconi Syndrome: A Rare Initial Presentation of Acute Lymphoblastic Leukemia. AB - A-14-year old boy, presented with a short history of excessive thirst and increased urine output. Clinical examination showed pallor, generalized lymphadenopathy and hepatosplenomegaly. For evaluation of his polyuric state he underwent routine laboratory investigations, including renal function test, acid base studies, urine analysis. Blood tests suggested hypokalemia, hypouricemia, hypocalcemia and hyperchloremia with normal liver and kidney function tests. The arterial blood gas analysis was suggestive of normal anion gap metabolic acidosis. Urine analysis was suggestive of hyperuricosuria, hypercalciuria and glycosuria with a positive urine anion gap. His hemogram showed pancytopenia with differential count showing 88% blasts. Bone marrow examination and flowcytometry confirmed the diagnosis of B cell acute lymphoblastic leukemia. Hence this case was atypical and very interesting in the sense that the Fanconi syndrome is very rare to be an initial presenting feature of acute lymphoblastic leukemia. The patient was started on oral as well intravenous supplementation with potassium, bicarbonate, calcium and phosphorus. Simultaneously, as per the modified BFM -90 protocol (four drug based regimen-Prednisolone, vincristine, daunorubicin, cyclophosphamide along with l-asparaginase), he was started on induction protocol. By the end of 3rd week of induction therapy, his urine output started normalizing and finally settled at the end of induction therapy. At present he is in the maintenance phase of chemotherapy. PMID- 27408344 TI - Atypical Presentation of Acute Lymphoblastic Leukemia in a 7 Year Old Child. AB - Seven year child, who had intussusception 4 month before, readmitted for fever and walking difficulty. On examination, child had mild pallor and kyphosis of the spine but no organomegaly, lymphadenopathy or bone pain . Further evaluation revealed hypercalcemia, diffuse osteoporosis with vertebral fracture. Peripheral smear showed no blasts or pancytopenia. Bone marrow aspiration turned out to be a pre B cell ALL. This child had many atypical presentations like intussusception, osteoporosis, vertebral collapse and hypercalcemia without any classical features of ALL. PMID- 27408345 TI - Concurrent Presentation of Therapy Related Acute Myeloid Leukemia in a Case of Neuroblastoma. AB - Therapy related Acute Myeloid Leukemia/Myelodysplastic syndrome (t-AML/MDS) occur due to the direct mutational events of the chemotherapeutic agents and radiotherapy. The disease latency, mutational events and prognosis vary with the type of chemotherapeutic agent. Therapy related Acute Myeloid Leukemia occurring with DNA topoisomerase II inhibitors have a shorter latency period and poor prognosis than anthracyclin based regimens. We report a case of a 9 year old boy who developed t-AML with mixed-lineage-leukemia gene translocation within a year of high dose chemotherapy for stage 4 neuroblastoma. He had residual mass of neuroblastoma in the abdomen and bone marrow. The patient expired within 2 weeks of induction chemotherapy. PMID- 27408346 TI - Bilateral Facial Nerve Palsy in Acute B Cell Lymphoblastic Leukemia: A Case Report and Review of the Literature. AB - Acute lymphoblastic leukemia (ALL) is a haematological malignancy that can involve the central nervous system (CNS). Less than 10 % of patients with ALL have CNS involvement at presentation. The cranial nerve most commonly affected is cranial nerve VII although bilateral involvement is rare. Management and outcomes of these patients are not well understood. Moreover bilateral Bells palsy as a presenting symptom of ALL is extremely uncommon. We report a very unusual presentation of ALL with bilateral facial nerve palsy, and discuss the management strategies and outcomes for patients with ALL that present with cranial nerve palsies. PMID- 27408347 TI - Therapy Related Acute Myeloid Leukemia with t(8;16) Mimicking Acute Promyelocytic Leukemia. AB - Acute myeloid leukemia (AML) with t(8;16)(p11;q13) is a distinct clinical and morphological entity with poor prognosis, which is characterized by a high frequency of extramedullary involvement, most commonly leukemia cutis; association with therapy related AML; frequent coagulopathy and morphologic features overlapping acute promyelocytic leukemia(APL). Herein, we present a case of 47 year-old post-menopausal woman developing secondary AML with t(8;16)(p11;q13) after 1 year of completion of therapy for breast carcinoma. Blasts were granulated with few showing clefted nucleus resembling promyelocytes and immnuophenotyping showed high side scatter with MPO positivity and CD 34 and HLA-DR negativity. In view of promyelocyte like morphology and immunophenotyping of blasts, possibility of APL was considered but, reverse transcription polymerase chain reaction (RT-PCR) for PML-RARalpha fusion transcript came out to be negative. Conventional cytogenetics showed t(8;16)(p11;q13). So, we should keep possibility of t(8;16) (p11;q13) in therapy related acute myeloid leukemia in patient showing clinical and morphological features of acute promyelocytic leukemia. PMID- 27408348 TI - Hemophagocytosis by Leukemic Blasts in T Cell Acute Lymphoblastic Leukemia: An Unusual Finding. AB - Hemophagocytosis shows engulfment of hematopoietic cells by histiocytes and is a property generally associated with cells of the histiocytic lineage. It can be familial or is seen in a wide spectrum of acquired disorders. Hemophagocytosis by leukemic blasts is an uncommon phenomenon and has been reported mainly in acute myeloid leukemia. Its association with acute lymphoblastic leukemia is rare. We present a case of hemophagocytosis by blasts in the bone marrow in a 11 year old boy with T cell-acute lymphoblastic leukemia. PMID- 27408349 TI - Effective Treatment of a Childhood Blastic Plasmacytoid Dendritic Cell Neoplasm with a Cutaneous Tumor Alone by Stem Cell Transplantation with Reduced Intensity Conditioning. AB - Pediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that has an extremely poor prognosis despite the use of intensive chemotherapy. Recently, treatment of BPDCN with bone marrow transplantation (BMT) using myeloablative conditioning has been reported to increase survival in adults. We report a 9-year-old girl with cutaneous BPDCN who was successfully treated with combination chemotherapy followed by BMT using reduced intensity conditioning (RIC), without any adverse complications. The success of this treatment regimen suggests that BMT with RIC may be a feasible option for treating children with cutaneous BPDCN. PMID- 27408350 TI - Fungal Mycotic Aneurysm in a Case of Acute Lymphoblastic Leukemia. AB - We report a case of a 15-year old boy who was managed as a case of B cell lymphoblastic leukaemia with the modified BFM 90 protocol. During the induction phase, he developed febrile neutropenia with sino-pulmonary fungal infection confirmed on histopathology. He developed left sided hemiparesis during in hospital management of febrile neutropenia. Neuroimaging revealed 9.6 * 8.4 mm round well defined aneurysm arising from right cortical artery in distal middle cerebral artery territory. He underwent fronto-temporo-parietal craniectomy with evacuation of the hematoma and excision of the aneurysm. Histopathological examination of excised aneurysmal specimen grew same species of fungus as was cultured from nasal scraping. He recovered fully in next 6 months with minimal residual focal neurological deficits. Presently he is in maintenance phase chemotherapy. We presented this case to illustrate a rare complication of ALL therapy with mycotic aneurysm secondary to invasive fungal infection treated successfully. PMID- 27408351 TI - The Successful Complete Remission Induction by Sorafenib Monotherapy in a FLT3 D835Y-Positive Patient with Refractory Acute Monocytic Leukemia. AB - Sorafenib has been shown to be active in AML patients with FLT3-ITD. However, the effect of sorafenib in AML patients with FLT-TKD has never been well determined. Moreover, acquisition of secondary FLT3 TKD mutations, mainly at D835 (D835F/H/V/Y), are recognized as the major mechanisms of resistance of AML patients with FLT3-ITD to sorafenib. It has been reported that sorafenib induced death of cells that expressed the FLT3-ITD or FLT3-D835G but not cells that expressed the FLT3-D835Y point mutant or wild-type FLT3 in vitro. Here, we report the successful complete remission induction by sorafenib monotherapy in a FLT3 D835Y-positive patient with refractory AML-M5 followed by allogeneic stem cell transplantation. PMID- 27408352 TI - All-Trans-Retinoic-Acid Unmasking Hypercalcemia of Hyperparathyroidism. AB - We present a patient of acute promyelocytic leukaemia managed with all-trans retinoic-acid and arsenic trioxide who developed hypercalcemia with target organ damage. The patient also was simultaneously discovered to be symptomatic from hyperparathyroidism, which was unmasked after ATRA administration. Patient was successfully managed without any interruption of ATRA therapy and parathyroidectomy. We discuss the mechanisms of ATRA in causing hypercalcemia and its possible role in index case in unmasking hyperparathyroidism. Present case refutes Occam's razor and emphasise that known adverse effects shouldn't withhold clinicians from working up for other common causes for a given condition. PMID- 27408353 TI - Aleukemic Leukemia Cutis Presenting as a Sole Sign of Relapsed Paediatric Acute Lymphoblastic Leukemia. AB - The author describes paediatric case of relapsed acute lymphoblastic leukaemia (ALL) presented as aleukemic leukaemia cutis (ALC). A 2 year old child was admitted in tertiary oncology centre. He suffered from pre B cell ALL with absent Philadelphia chromosome. This patient received multiagent induction chemotherapy as per Berlin-Frankfurt-Munster (BFM) protocol for ALL. He achieved remission after 28 days of treatment. Subsequently he presented with multiple skin lesions in the form of multiple small erythematous violaceous macules, papules, plaques and nodules on face, chest and back regions. Histopathological examination of biopsy of skin revealed diffuse infiltration of tumor cells with prominent nucleoli, scant eosinophilic cytoplasm and numerous mitotic figures consistent with LC. Immunohistochemistry was positive for CD 10, CD 19, CD 22, CD 24, CD 79 a and TdT while negative for surface immunoglobulin. At the time of presentation his peripheral blood smear and bone marrow examination was negative for malignant cells. Sanctuary sites including central nervous system and testicles were not involved. So patient was diagnosed as ALC. He was managed as per BFM relapse protocol for ALL. Skin lesions disappeared completely after 2 weeks of treatment. Unfortunately patient developed bone marrow and testicular relapse after 2 months. He was given testicular radiotherapy and systemic chemotherapy for relapsed ALL. But his marrow was showing persistent activity and he expired after 4 months. PMID- 27408354 TI - Acute Lymphoblastic Leukemia in the Course of Polycythemia Vera: A Case Report and Review of Literature. AB - INTRODUCTION: Polycythemia vera (PV) is one of the most common forms of myeloproliferative neoplasms. Acute myeloid leukemia secondary to PV is well reported, and the mechanism has been clarified to some extent. Only a limited number of cases have been reported about the development of acute lymphoblastic leukemia (ALL) in the course of PV, and the possible underlying mechanism has not been explored well. CASE PRESENTATION: A 75-year-old patient who developed ALL 3 years after he was diagnosed with PV. The presence of remarkable splenomegaly, typical immunophenotyping of the peripheral blood and increased expression of serum fibrosis markers indicated the existence of extramedullary hematopoiesis which may ascribe to myelofibrosis. After the treatment of dosage-modulated chemotherapy, the patient got complete remission. CONCLUSION: The JAK2 mutation may the underlying factor that contributes to the development of ALL, and the existence of MF may indicate the progression to post- polycythemic MF, which may be a risk factor for the accelerated transformation. PMID- 27408355 TI - Treatment of an Elderly Patient with Acute Myeloid Leukemia and Invasive Pulmonary Aspergillosis Infection with Combined Allogeneic Hematopoietic Stem Cells Microtransplantation and Voriconazole. AB - Invasive aspergillosis infection (IF) in patients with hematologic malignancies is common. Prognosis of IF in patients with acute myeloid leukemia (AML) not responsive to chemotherapy is very poor, especially when neutropenia is duration. Fractional HLA haplo-identical mobilized neutropenia peripheral blood stem cell (PBSC) transfusion, which was defined as micro-transplantation, was recently adopted in treatment of elder patients with AML and shown to be effective in fasting hemopoiesis recovery. Here we report the outcome of an elderly patient with AML accompanying IF treated with microtransplantation and voriconazole. The patient (female, age 62) was diagnosed relapsed AML accompaning suspected invasive fungal infection. She refused to accept further chemotherapy. PBSC from her daughter were collected and transfused fractionally. Voriconazole was used for anti- aspergillosis treatment. After stem cell infusions, the patient's neutrophil count increased, and platelet transfusion interval extended from 3-4 to 10-14 days. Lung CT indicated that the lesions were significantly absorbed. The patient survived for 257 days. We concluded that for elderly patients with AML and accompanying IF who are not eligible for chemotherapy, microtransplant may be beneficial for improving the efficacy of anti-fungal treatment. PMID- 27408356 TI - Clinical Presentation of Inadvertent Intrathecal Vincristine Masquerading Guillain-Barre Syndrome. AB - Vincristine, a potent chemotherapeutic agent, is highly neurotoxic. If given intrathecally by accident it is almost always fatal. We are reporting a 6 year old girl with acute lymphoblastic leukaemia in complete remission, who was given inadvertent intrathecal Vincristine instead of Methotrexate. She developed gradually progressive quadriplegia and respiratory paralysis requiring prolonged mechanical ventilation, initially mimicking Guillain-Barre Syndrome, both clinically and electro-physiologically. She also developed progressive encephalopathy. The clinical deterioration subsequently plateaued without any significant improvement and after more than 5 months, she finally expired. PMID- 27408357 TI - Acute Lymphoblastic Leukemia Transformation in Polycythemia Vera: A Rare Phenomenon. AB - Leukemic transformation in patients diagnosed with polycythemia vera (PV) is associated with poor prognosis and median survival not exceeding 3 months. To date only a few cases of post-PV acute lymphoblastic leukemia (ALL) have been reported. A 64-year-old female patient developed ALL 4 years after she had met PV criteria. At PV diagnosis a molecular study was positive for the JAK2V617F mutation. Due to high risk features (history of deep vein thrombosis) she was treated with hydroxyurea (HU) with moderate efficacy. She became anemic and thrombocytopenic with mild leukocytosis while still on HU. Blood and bone marrow smears revealed 40 and 100 % of blast cells, respectively. The immunophenotyping of blasts was consistent with a diagnosis of early precursor B cell ALL. She was found to be positive for the JAK2V617F mutation. Patient received an ALL induction regimen and achieved complete remission with negative minimal residual disease by flow cytometry. The post-chemotherapy study for the JAK2V617F mutation was positive. Patient has remained in remission for 4 months. A suitable donor searching was initiated. Post-PV ALL is an extremely rare phenomenon. Due to poor prognosis, an allogeneic stem cell transplantation should be considered in fit patients who achieved remission. PMID- 27408358 TI - Leukemia in Patients with Klinefelter Syndrome: A Report of Two Cases. AB - Klinefelter syndrome (KS) is a chromosome abnormality characterized by a 47, XXY karyotype associated with hypogonadism and infertility. We present two cases of leukemia in patients with KS. The first patient presented with acute promyelocytic leukemia. He relapsed after the end of treatment. The second patient was diagnosed with chronic myeloid leukemia. Treatment with imatinib failed and the patient presented with myeloid blast crisis. PMID- 27408359 TI - Myeloid Sarcoma Of Vulva: A Short Update. PMID- 27408360 TI - Mixed Phenotypic Acute Leukemia Presenting as Mediastinal Mass-2 Cases. AB - Mixed phenotype acute leukemia symbolizes a very small subset of acute leukemia that simply cannot be allocated as lymphoid or myeloid lineage. The 2008 World Health Organisation classification established stringent standard for diagnosis of mixed phenotype acute leukemia, accentuating myeloperoxidase for myeloid lineage, cytoplasmic CD3 for T lineage and CD19 with other B markers for B lineage obligation. Mixed phenotype leukemia is rare and 3-5 % of acute leukmias of all age groups, is associated with poor outcome with overall survival of 18 months. We wish to present two cases of mixed phenotypic acute leukemia who presented with mediastinal masses, were suspected to be T cell lymphoma/leukemia clinically and radiologically. In one case, tissue diagnosis was given as lymphoma for which treatment was given. These cases show that patients diagnosed as lymphoma on histopathology can be cases of mixed phenotype acute leukemia and varying specific treatment protocols and follow up are required. Awareness of these entities will help in proper diagnosis and treatment. PMID- 27408361 TI - APL-The Age-Old Harlequin: Do We See it All? PMID- 27408362 TI - Development of Acute Promyelocytic Leukemia in a Patient With Gouty Arthritis on Long Term Colchicine. AB - Colchicine is a frequently used drug in rheumatological diseases. Acute promyelocytic leukemia developed in a patient who used colchicine for gouty arthritis since 10 years is presented and the possible relation between the long term use of colchicine and hematological malignancies is discussed. PMID- 27408363 TI - Recurrent Sweet's Syndrome in a Case of AML. PMID- 27408364 TI - De Novo Philadelphia Positive Acute Myeloid Leukemia with Extensive Basophilia: A Diagnostic Dilemma. AB - Basophilia in peripheral blood as well as bone marrow is an unusual finding, seen in certain reactive and neoplastic conditions. Amongst the malignant hematological diseases, it is a diagnostic hall mark of chronic myeloproliferative disorders, particularly, chronic myeloid leukemia. Basophilia may also be seen in cases acute myeloid leukemia, particularly FAB AML M2 and M4. Here we document an interesting case of de novo acute myeloid leukemia which had extensive peripheral blood and bone marrow basophilia. Molecular analysis revealed p190, bcr-abl fusion transcript. A short clinical course, absence of organomegaly and features suggestive of an underlying myeloproliferative disorder, aided in establishing a diagnosis of Philadelphia positive de novo acute myeloid leukemia. PMID- 27408365 TI - Chronic Myeloid Leukemia with Extramedullary Blast Crisis: Two Unusual Sites with Review of Literature. AB - Extramedullary blast crisis (EBC) in chronic myeloid leukemia (CML) is a rare phenomenon and represents infiltration of leukemic blasts in areas other than bone marrow. Lymph node is the most common site of involvement by EBC. We herein present a case of CML who suffered from two discrete episodes of EBC at atypical locations (scalp and paravertebral) within an interval duration of nine months. A 38-year-old female was diagnosed as a case of CML with extramedullary blast crisis in scalp at presentation. She received treatment with imatinib 600 mg once daily through Novartis Oncology Access Program (NOA). She achieved hematological remission. However nine months later she was readmitted with spinal shock due to cord compression secondary to paraspinal chloroma. She was started on tablet Nilotinib in view of failure to 1st line therapy. Her compressive myelopathy was treated with pulses of high dose dexamethasone. However soon she died due to pneumonia. PMID- 27408367 TI - "Unusual Cause Of Tophi With Renal Thrombotic Microangiopathy". AB - Chronic neutrophilic leukemia (CNL) is a rare entity amongst myeloproliferative neoplasms (MPNs). The classical presentation of CNL is with splenomegaly, mature neutrophilic leucocytosis and hyperuricemia. We herein report a case who presented with symptoms of acute gouty arthritis. Physical examination showed typical red, tender tophi in the right hand, right foot and both pinnae suggesting an acute episode of gout. During evaluation, moderate splenomegaly, mature neutrophilia, hyperuricemia and sub-nephrotic range range proteinuria were noted. Bone marrow examination and kidney biopsy was done. Final diagnosis of CNL with acute gouty arthritis and chronic renal thrombotic microangiopathy (TMA) was made. Although hyperuricemia is a common finding in MPNs but presentation of our case with symptoms of acute tophi and chronic TMA is atypical. PMID- 27408366 TI - A Case of Dasatinib-Induced Hemorrhagic Colitis Diagnosed by the Lymphocyte Transformation Test in a Chronic Myeloid Leukemia Patient. AB - Dasatinib is an effective treatment option for patients diagnosed with Philadelphia chromosome positive chronic myeloid leukemia and who are non responsive or intolerant to imatinib treatment. Dasatinib, however, is associated with various adverse effects and on rare occasions, may cause hemorrhagic colitis. We report the case of a 68-year-old male patient with dasatinib-induced hemorrhagic colitis, the first such case in Korea. Endoscopic biopsy of the transverse colon demonstrated non-specific inflammatory changes only. Cessation of dasatinib led to the resolution of symptoms, while reintroduction of the therapy led to the recurrence of his bloody diarrhea. To clarify the association between dasatinib and hemorrhagic colitis, the lymphocyte transformation test (LTT) was performed. The LTT result sustained a relatively high proliferation activity in the affected patient compared with almost no proliferation activity in normal control. PMID- 27408368 TI - Chronic Myeloid Leukemia Developing After Successful Treatment of Acute Promyelocytic Leukemia. AB - Acute promyelocytic leukemia (APL) has been regarded as a highly curable disease. Therapy-related leukemia is one of the important late complications that affect long-term survival rates in APL patients. Therapy-related acute myeloid leukemia and myelodysplastic syndrome are the major forms of therapy-related leukemias. We report a rare event of chronic myeloid leukemia (CML) that developed after successful treatment of APL with all-trans-retinoic acid in combination with chemotherapy. Rather unexpectedly, CML developed 7 years after APL. Cytogenetic and molecular studies proved the independence of these two entities. It was found that CML progressed rapidly after a short-term response to a combination therapy with hydroxyurea, interferon-alpha and arsenic trioxide. We propose that optimization of chemotherapy regimen and treatment intensity may reduce the risk of developing a secondary leukemia, while long-term monitoring cytogenetics of APL patients after treatment may help determine the development of a secondary leukemia at early stage. PMID- 27408369 TI - Systemic Mastocytosis with Associated Clonal Hematological Non-Mast Cell Lineage Disorder (MDS-RCMD): A Difficult Disease to Diagnose and Treat. AB - Systemic mastocytosis is a rare and recalcitrant disorder with nonspecific clinical features. Hence, a high index of suspicion is required. Here, we report the case of a 64 years old male presenting with chronic diarrhoea that was evaluated at different centres and treated with multiple lines of therapy. The diagnosis of aggressive systemic mastocytosis was finally clinched following a holistic work up that included a Jejunal biopsy and a laparoscopic lymph node biopsy. Treatment of this disorder is difficult, responses are transient and most patients will eventually relapse, as illustrated by this case. Cladribine, Interferon alpha, steroids and imatinib have limited success in the management of this disease. The role of stem cell transplant is uncertain. PMID- 27408370 TI - Coexisting JAK2V617F and CALR Exon 9 Mutation in Essential Thrombocythemia. AB - Classic "BCR-ABL1-negative" MPN is an operational sub-category of MPN that includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) harboring JAK2V617F as the most common mutation. JAK2V617F can be detected in about 95 % of patients with PV while remaining 5 % of PV patients carry a somatic mutation of JAK2 exon 12. Approximately one-third of patients with ET or PMF do not carry any mutation in JAK2 or MPL. In December 2013, mutations were described in calreticulin (CALR) gene in 67-71 and 56-88 % of JAK2V617F and MPL negative patients with ET and PMF, respectively. Since this discovery CALR mutations have been reported to be mutually exclusive with JAK2V617F or MPL mutations. However recently few studies (eleven published reports) reported the coexistence of JAK2V617F and CALR in MPN. In the present study we are reporting JAK2V617F positive ET patient from our center with coexisting CALR exon 9 mutation type c.1214_1225del12 (p.E405_D408del) that was never reported before as a coexisting mutation and describing in detail the clinical outcomes. PMID- 27408371 TI - Obstructive Uropathy as an Initial Presentation of Primary Myelofibrosis: Case Report and Review of Literature. AB - Primary myelofibrosis (PMF) is a rare hematological disorder associated with progressive cytopenia and extra-medullary hematopoiesis. Acute kidney injury in this disease has been reported from diverse etiologies such as renal and peri renal extramedullary hematopoiesis and tumor lysis syndrome. We report a patient who presented with obstructive uropathy from uric acid stones who was incidentally diagnosed with PMF during workup for persistent thrombocytosis and leukocytosis. Marrow histopathology was unique in presenting features of early PMF despite clinical picture mimicking essential thrombocythemia. Despite a common background of hyperuricemia in myeloproliferative neoplasms, AKI resulting from urate nephrolithiasis has seldom been reported in PMF. Published data on this association and clinical management is reviewed briefly. PMID- 27408372 TI - CD56 Negative Aggressive T Cell Large Granular Lymphocytic Leukemia. AB - T cell large granular lymphocytic leukemia is a clonal proliferation of cytotoxic large granular T cells positive for CD3 and CD8. It is a chronic lymphoproliferative disorder with an indolent course. Therapeutic options include observation and low dose chemotherapy. Rarely, they have an aggressive course. Such cases have expression of NK cell associated antigens like CD56 in the T cells. These cases require more aggressive therapy with acute lymphoblastic leukemia regimens. We report a case of fatal CD56 negative T cell large granular lymphocytic leukemia in a 38 year old lady. PMID- 27408373 TI - Aggressive Lymphomas Diagnosed in the Bone Marrow: Two Illustrative Cases. AB - Lymphomas with subtle patterns in the marrow can be a diagnostic challenge, unless a high index of suspicion is maintained. We present two patients with aggressive lymphomas who presented with cytopenias and the subsequent bone marrow examinations yielded surprising results. These cases highlight the potential usefulness of a bone marrow examination in the diagnosis of lymphomas in the absence of nodal or other tissue specimens. PMID- 27408374 TI - Plasmablastic Lymphoma of Small Intestine: A Rare Case Report with Review of Literature. AB - Plasmablastic lymphoma (PBL) is a rare aggressive neoplasm characterized by diffuse proliferation of large neoplastic cells with plasma cell immunophenotype. Cell of origin of PBL is believed to be a postgerminal center B-lymphocyte or plasmablast. The malignant cells in PBL usually do not express CD20 (B cell marker) but do express markers of plasmacytic differentiation, such as CD38, CD138, or MUM1/IRF4, akin to plasma cell myeloma (PCM). PBL though originally described in the oral cavity, has now been found to occur in extraoral locations as well. Small intestine as a site of PBL has been described very rarely. PBL remains a diagnostic challenge given its overlapping morphologic and immunophenotypic features with other high grade lymphomas and PCM. We report a rare case of PBL of small intestine in a 48 years old HIV infected male patient. To the best of our knowledge this represents sixth case in the literature described in this location. An unusual rare pattern of CD138 positivity by IHC is also reported along with extensive review of literature of PBL in extraoral locations. PMID- 27408375 TI - Clivus and Dural Involvement in a Case of Multiple Myeloma: A Rare Complication of Multiple Myeloma. PMID- 27408376 TI - Flow Cytometry in Diagnosis of Myelomatous Pleural Effusion: A Case Report. AB - Plasma cell myeloma is a multifocal plasma cell neoplasm associated with increased monoclonal protein in serum and/or urine. Pleural effusions in patients with myeloma are uncommon (6 %). However, effusions due to direct infiltration of the pleura by plasma cells (myelomatous pleural effusion) are extremely rare (<1 %) and usually seen with IgA myeloma. The diagnosis of such cases requires pleural fluid cytology, electrophoresis or pleural biopsy. We present a case of myelomatous pleural effusion diagnosed using flow cytometry immunophenotyping in addition to the pleural fluid cytology. A 45 year old female was diagnosed as plasma cell myeloma (IgG kappa) in 2007. She received multiple lines of therapy during the course of her treatment including thalidomide, dexamethasone, lenalidomide, bortezomib, and doxorubicin based regimens. However, the patient had progressive extramedullary disease and developed pleural effusion in 2014. Cytological examination of the pleural fluid showed degenerative changes. Few preserved areas showed mononuclear cells including morphologically abnormal plasma cells. Immunophenotyping of these cells by flow cytometry revealed a pattern indicating neoplastic plasma cells. There was expression of CD38, CD138, and CD56, with absence of CD19, CD10 and CD45. This confirmed the diagnosis of myelomatous pleural effusion. Subsequently, the patient was offered a dexamethasone, cyclophosphamide, etoposide and cisplatin based regimen but, she declined further treatment and succumbed to her disease 3 months later. Myelomatous pleural effusion is a rare complication of plasma cell myeloma. Flow cytometry can be used as an adjunctive technique in its diagnosis particularly in cases with equivocal cytology and electrophoresis findings. PMID- 27408377 TI - Primary Intraocular Diffuse Large B-cell Lymphoma: Diagnostic Difficulties in Deep Retinal Infiltrations with Vitritis. AB - PURPOSE: Primary intraocular lymphoma (PIOL) is a rare malignancy with an aggressive clinical course. It is usually considered as a subset of primary central nervous system lymphoma. Differential diagnosis should include infectious and non-infectious aetiologies, particularly the common masqueraders sarcoidosis, tuberculosis, viral retinitis and syphilis. PATIENT: The article presents a case of bilateral vitreoretinal lymphoma manifesting as uveitis and vitritis resistant to corticosteroid therapy. The final diagnosis was based on a retinal biopsy. RESULTS: The patient was successfully treated with systemic and local therapy. Long-term complete remission (CR) was reached. The relapse of diffuse large B cell lymphoma was revealed in the frontal left lobe after 48 months of CR duration. CONCLUSION: The diagnosis of PIOL is always very difficult. Cooperation of pathologists, ophthalmologists and hematologists is required for a quick and accurate diagnosis. Local and systemic treatment is needed to achieve CR, but the relapse rate remains very high. PMID- 27408378 TI - Immunoglobulin M 'Flare' Seen in a Case of Waldenstrom's Macroglobulinemia: Successfully Managed by Therapeutic Plasma Exchange. AB - Therapeutic plasma exchange (TPE) is a conjunctive modality of treatment along with rituximab to decrease paraproteinemia associated with hyperviscosity. Here we narrate our experience in treating a diagnosed case of Waldenstrom's macroglobulinemia in 70 years old male patient with moderate anemia and severe features of hyperviscosity syndrome by serial TPE and rituximab combined with bortezomib. The patient was relieved of his symptoms after initial two TPE procedures performed on alternative day. However he again developed signs and symptoms of the disease within 6 weeks following second TPE and starting of rituximab (375 mg/m(2) weekly for 4 weeks) therapy with bortezomib. His serum IgM level became as high as 9.901 g/dl suggesting immunoglobulin M 'Flare' due to rituximab therapy. At the end of third TPE he was relieved symptomatically with low IgM level (3.13 g/dl) and discharged in hemodynamically stable condition. Therefore we concluded that careful monitoring of serum viscosity and IgM level are necessary during treatment with rituximab based chemotherapy and TPE should be promptly initiated to control the treatment related hyperviscosity syndrome. PMID- 27408379 TI - Bilateral Tonsillar Enlargement as a First Manifestation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with an Unusual Interfollicular Pattern of Infiltration. AB - Tonsillar lymphoma usually presents as unilateral or bilateral enlargement or as an ulcerative or fungating lesions. Most lymphomas that involve the tonsils are diffuse large B-cell lymphomas and primary low grade lymphomas are exceptional. We report a case of primary B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) affecting tonsils with interfollicular pattern of infiltration in a 54-year-old female who clinically presented with bilateral tonsillar enlargement, sore throat, dysphagia and respiratory difficulty, unresponsive to the conservative treatment. To the best of our knowledge, till date only six cases of CLL/SLL infiltrating tonsils have been reported in the English literature, three of these were known cases of CLL/SLL prior to tonsillectomy. In the present case diagnosis of CLL/SLL was first time established on tonsillar histomorphology and that too with an unusual interfollicular pattern of infiltration. PMID- 27408380 TI - A Case of Chronic Lymphocytic Leukaemia Occurring During Treatment of Chronic Myeloid Leukaemia. PMID- 27408381 TI - A Case Presenting with Splenic Infarct Diagnosed as Primary Bone Marrow CD5 Positive DLBCL: A Clinicopathological Correlation. AB - De novo CD5+ Diffuse large B cell lymphoma (DLBCL) is a rare and aggressive subtype of DLBCL. It is a distinct clinicopathologic entity with complex molecular profile and poor prognosis. A 59 year old female presented with pyrexia of unknown origin since 1 month. On examination, there was severe pallor, hepatosplenomegaly and no palpable lymphadenopathy. Complete blood count revealed bicytopenia with normal total leucocyte count. Liver and renal function tests were normal. Ultrasonography abdomen revealed splenic enlargement with two focal lesions attributed to either splenic abscess or infarcts. Patient was being managed as splenic infarct but continued to have bicytopenia. Further investigation showed elevated serum ferritin, triglycerides and LDH. With a clinical suspicion of infection and haemophagocytic lymphohistiocytosis bone marrow aspiration (BMA) and biopsy (BMBx) was done. BMA showed extensive haemophagocytosis and ~7.4 % large lymphoma-like cells. On this basis PET-CT was suggested which showed enlarged spleen with diffuse uptake. BMBx showed nodular and intrasinusoidal collection of abnormal lymphoid cells. On immunohistochemistry, these cells were positive for CD20, CD5, MUM1, BCL-2, BCL-6 and negative for CD3, CD10 and CD23. CD34 highlighted focal intrasinusoidal pattern. The complete clinicopathological profile suggested the diagnosis of de novo CD5+ DLBCL, with primary hepatosplenic pattern of involvement. CD5+ DLBCL presenting as splenic infarct is very rare. This case was unusual as the diagnosis of a primary aggressive lymphoma with haemophagocytosis was established in a patient who presented with fever and splenic infarct without lymphadenopathy. This indicates the importance of good morphological assessment of a bone marrow aspirate and biopsy to make a correct diagnosis. PMID- 27408382 TI - Rare Occurrence of 3 "H": Hypercalcemia, Hemolytic Anemia and Hodgkin's Lymphoma. AB - Clinicians in hematology practice commonly encounter anemia, hypercalcemia and renal failure, which when present in combination evoke a diagnostic workup for multiple myeloma. We report a 71-years old lady who presented to our hematology clinic with fever and easy fatiguability of 3 months duration and on investigations was found to have anemia and hypercalcemia. Direct Coomb's test characterized the anemia as complement mediated (anti-C3d) hemolysis. Biochemical investigations revealed normal 25(OH) Vitamin D3 and suppressed Parathormone levels and a negative workup for plasma cell dyscrasias, sarcoidosis and autoimmune disorders. CT scan revealed a paravertebral mass with cervical, supraclavicular and abdominal lymphadenopathy along with splenomegaly and left pleural effusion. Biopsy from the paravertebral mass confirmed the diagnosis of Hodgkin's disease (nodular sclerosis) using immunohistochemistry. Bone marrow examination suggested infiltration by lymphoma. Hypercalcemia was managed with saline and zoledronic acid. Administration of prednisolone (1 mg/kg/day) along with chemotherapy (ABVD regimen) led to normalization of calcium and hemoglobin levels. However, hemolysis recurred 2 weeks later and hence, Rituximab (375 mg/m(2)) was administered on a weekly schedule for 4 doses and ABVD (2 weekly) was continued, which brought hemolysis under control. Co-occurrence of two paraneoplastic manifestations (complement mediated hemolytic anemia and hypercalcemia) in Hodgkin's lymphoma is very unusual. Present report aims not only to highlight a rare presentation of Hodgkin's lymphoma but also focus on the role of Rituximab in controlling hemolysis associated with this disease. PMID- 27408383 TI - Synchronous Plasma Cell Myeloma and Acute Myeloid Leukemia in a Therapy-Naive Patient: A Rare Occurrence. AB - Plasma cell proliferations in patients with acute myeloid leukemia (AML) are rare, whether at presentation or during or after therapy. Interpretation requires correlation with the clinical background, drug history as well as inputs from tests for monoclonal gammopathy and end-organ damage. The major diagnostic issues stem from excluding myeloma alone with a plasmablastic morphology that mimics AML as well as reactive or polyclonal plasmacytosis occurring in a bonafide case of AML alone before rendering a rare diagnosis of true dual pathologies. We report a rare case of concurrent AML and plasma cell myeloma in a 55-year-old lady that posed a significant diagnostic challenge. The patient had significant co morbidities complicating the clinical picture and was treatment-naive at the time of diagnosis. Our approach to confirming the diagnosis, as well the challenges faced in flow cytometric analyses are highlighted. The pathogenesis of such dual pathologies remains unresolved, although various conjectures and theories have been propounded in literature. PMID- 27408384 TI - Concomitant Presence of Two Distinct Clones of Chronic Lymphocytic Leukemia and Plasma Cell Myeloma in a Patient. AB - A 74 years old male patient, presented with history of generalized weakness, fatigue, loss of appetite and breathlessness on exertion for past one and a half months. On examination, he was found to have significant pallor and generalized lymphadenopathy (cervical, axillary and inguinal). The skeletal survey showed punched out lytic lesions in skull and pelvic bones. The peripheral smear examination showed lymphocytosis with absolute lymphocyte count of 25,000/MUL. The bone marrow aspirates revealed a hypercellular marrow with 74 % lymphocytes & 14 % plasma cells, suggestive of chronic lymphoplasmacytic disorder. The bone marrow biopsy had two morphologically distinct populations of lymphocytes & plasma cells. The immunohistochemical markers on bone marrow biopsy showed hat plasma cells were positive for CD138 with kappa light chain restriction. Flow cytometry showed B cell population with CD19/CD5 co expression, CD5/CD23 coexpression, were positive for CD22, CD20 and negative for FMC-7 and lambda light chain. In addition, plasma cells were also identified as CD45 negative cells and showed CD38/CD138 co-expression with variable CD19 and CD56 positivity. Serum protein electrophoresis revealed M band, serum immunofixation electrophoresis corresponded to IgA -Kappa. The final diagnosis of chronic lymphocytic leukemia with concomittant presence of plasma cell myeloma was concluded. This case imparts an important message to look for presence of coexisting entities in a single specimen and highlights the benefits of testing both plasma cell and B-cell compartments when the clinical features are not entirely consistent Flow cytometry together with protein electrophoresis can help to clinch difficult and rare dual diagnosis. These cases are rare and pose therapeutic challenge. PMID- 27408385 TI - Complete Remission of Burkitt Lymphoma After Surgical Excision: A Case Report. AB - Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma that has a high proliferation rate. The prognosis for BL is generally favorable, with cure rate of 75-90 % with modern chemoimmunotherapy regimens. Prompt administration of multiagent immunochemotherapy regimens is critical, because BL is almost always fatal if left untreated. Nevertheless here we report a case of BL that is still in complete remission after more than 4 years without any further treatment after surgical excision of the involved lymph node. PMID- 27408386 TI - Cholestasis in a Patient of Multiple Myeloma: A Rare Occurrence of Bortezomib Induced Liver Injury. PMID- 27408387 TI - Occurrence of Double Monoclonal Bands on Protein Electrophoresis: An Unusual Finding. AB - Various techniques of protein electrophoresis are used for detection of monoclonal proteins/paraproteins in serum and/or urine of patients with monoclonal gammopathies. These are detected as the so-called 'M' bands (monoclonal bands) on serum protein electrophoresis and/or immunofixation electrophoresis. In most cases, a single M-band is detected. However, more than one M-band can be detected in the samples of a minor proportion of patients. This condition is termed as 'double gammopathy' or 'biclonal gammopathy'. A knowledge of such an unusual occurrence is essential for recognition and appropriate interpretation of this entity. PMID- 27408388 TI - Ascites as a Manifestation of GVHD: a Rare Phenomenon. AB - Graft versus host disease (GVHD) usually have involvement of classical target organs. Manifestations of Chronic GVHD (cGVHD) are much more protean than acute GVHD. NIH consensus criterion for cGVHD proposes different diagnostic and distinctive features of cGVHD. It acknowledges certain uncommon manifestations that can be attributed to cGVHD only when they are associated with more specific features. Patients rarely may develop such manifestations which are not diagnostic of cGVHD themselves. In the absence of more specific features of cGVHD, they may pose diagnostic challenge. Amongst the rare reported manifestations of cGVHD is serositis manifesting as pleural effusion, pericardial effusion or ascites. We report two patients developing ascites as an isolated manifestation of cGVHD. PMID- 27408389 TI - Glioblastoma Multiforme in a Post Allogeneic Stem Cell Transplant Patient. A Case Report and Literature Review of Post Transplant Neurological Tumors. AB - Seventeen year old boy, a case of relapsed acute lymphoblastic leukemia 10 years post allogeneic transplantation, presented to us with acute onset of right hemiparesis. The imaging revealed contrast enhancing lesion in the frontal lobe, biopsy of the same was consistent with glioblastoma multiforme (GBM). He had received total body irradiation (TBI) based conditioning regimen prior to transplant. GBM was treated with left parietal craniotomy and parietal excision of tumour, followed by radiation therapy with concurrent and adjuvant chemotherapy. Disease progressed while was on adjuvant chemotherapy and patient succumbed to his illness 8 months after the diagnosis of GBM. We report here a here unusual case of GBM in a post transplant patient who received TBI based conditioning regimen. PMID- 27408390 TI - A Rare Case of Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Patient. AB - Post bone marrow transplant patients are susceptible to atypical infections, especially viral pathogens. The risk increases many folds in cases of allogeneic transplantation, which also receive GVHD prophylaxis. Viral pathogens like cytomegalovirus and herpes are the common ones encountered during follow-up period. However, in recent times there have been reports of a variety of disease manifestations of rare viruses like polyoma virus and adenovirus. These viral infections may play a crucial role in morbidity and mortality in immunocompromised patients. We hereby elaborate the follow-up course of a 36-year old post allogeneic transplant patient of acute myeloid leukemia who developed adenovirus related haemorrhagic cystitis. Treatment with oral ribavirin lead to dramatic improvement in symptomatology within a week. This cases re-emphasizes the fact that after ruling out the commoner pathogens, it's of utmost importance to strongly consider the atypical pathogens in such cases. PMID- 27408391 TI - Isolated Breast Relapse of Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation. AB - Isolated breast relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is less often seen. Chronic graft-versus-host disease (cGVHD) is effective in preventing marrow relapse, but cGVHD seems not to be effective extramedullary relapse (EMR). We report the case of isolated breast relapse after first allo-HSCT for acute lymphoblastic leukemia (ALL). A 47-year-old female was diagnosed with ALL achieved complete remission with salvage chemotherapy and underwent allo-HSCT from an HLA-matched sibling male donor. At 17 months post transplant, she presented with a bilateral breast masses that confirmed the diagnosis lymphoblast involvement. She had no evidence of leukemia in her marrow that determined 100 % full-donor chimerism when she was relapsed in her both breasts. PMID- 27408392 TI - Hematopoietic Stem Cell Transplant in Elderly Patients: Experience from a Tertiary Care Centre in Northern India. PMID- 27408393 TI - Importance of Clinically Significant Anti-M Antibody in Hematopoietic Stem Cell Transplantation. AB - Naturally occurring anti-M antibodies are mostly of the IgM class, however, an IgG component can also be present along with IgM. The IgM anti-M antibodies can be ignored if they are not reactive at 37 degrees C, but the patient should receive M antigen-negative red blood cells if the antibody is reactive at 37 degrees C or if it is of IgG class. Here we discuss a case of clinically significant naturally occurring anti-M antibody had both IgM and IgG components in a 3 years old child who was a hematopoietic stem cell donor for her 6 years old sister suffering from beta-thalassemia major. The specificity and immunoglobulin class of the antibody was confirmed by antibody screening at wide thermal range, dithiothreitol treatment of serum and reaction of serum with enzyme treated panel cells. PMID- 27408394 TI - Blood Group Discrepancy-First Sign of Autoimmune Hemolytic Anemia after Hematopoietic Stem Cell Transplantation in a Child. AB - A 12-year-old male child was presented in the emergency with features of anemia and mild icterus on day+67 of HSCT. The child was suffering from Fanconi anemia and undergone HSCT from ABO-matched, fully HLA matched sibling donor. The diagnosis of mixed type AIHA due to cytomegalovirus reactivation was made in the immunohematology laboratory and blood group discrepancy was the first sign of AIHA in this patient. Though the cold agglutinin titer was not significant but the clinical symptoms and laboratory evidences were suggestive of significant hemolysis due to underlying IgG autoantibody. In addition the high complement avidity of IgM autoantibody might also be a contributing factor for clinically significant hemolysis in this case. The patient was successfully treated with phenotype matched blood transfusion, rituximab and oral steroid therapy. PMID- 27408395 TI - Methimazole Induced Total Myeloid Aplasia with Delayed Recovery Despite Granulocyte Colony Stimulating Factor (G-CSF): Marrow Progenitor Recovery Kinetics. AB - An eighteen-year-old female with Graves thyrotoxicosis presented with methimazole induced agranulocytosis and total myeloid aplasia. The bone marrow at presentation showed complete absence of myeloid precursors and striking plasmacytosis. 16 days later, myeloid precursors were still absent morphologically; however bone marrow flow cytometry and cell culture detected an improvement in myelogenesis, which was soon followed by clinical recovery of agranulocytosis. Neutrophil recovery was delayed until day 22 after cessation of methimazole despite G-CSF use, consistent with a direct toxic effect on committed myeloid cells. Our findings suggest that cell culture and flow cytometric evaluation of bone marrow myeloid progenitors can be used as a guide to anticipate neutrophil recovery. PMID- 27408396 TI - Thymoma with Concomitant Pure Red Cell Aplasia, Good's Syndrome and Myasthenia Gravis Responding to Rituximab. AB - Thymomas are often associated with a variety of autoimmune diseases, mostly myasthenia gravis. The association of thymomas with both pure red cell aplasia (PRCA) and Good's syndrome is exceedingly rare. To the best of our knowledge, the combination of a thymoma with manifestations of myasthenia gravis, PRCA, and Good's syndrome, as in our case herein, has not been described before in the medical literature. We present a 90-year-old man initially diagnosed with an asymptomatic thymoma. Later, he developed generalized muscle weakness and was found to have severe anemia. He was diagnosed with PRCA, myasthenia gravis and Good's syndrome. He responded to rituximab with restoration of bone marrow erythroid maturation and stabilization of red blood cell counts. PMID- 27408397 TI - Leukemic Transformation of Severe Aplastic Anemia Following Matched Allogenic Stem Cell Transplantation, Transplanted Again in CR 1. AB - Aplastic anemia (AA) is a life-threatening bone marrow failure disorder, if untreated, is associated with very high mortality. Allogenic bone marrow transplantation (BMT) is the standard of care for severe aplastic anemia (SAA) patients those who are younger than 40 years of age. The development of secondary malignancies in post-BMT setting for AA is a rare, however, well documented phenomenon. Among the secondary malignancies, development of acute myeloid leukemia is even rarer entity. Here we report a case of acute myeloid leukemia following human leucocyte antigen (HLA) matched sibling peripheral blood stem cell transplant (PBSCT) in a case of SAA. The patient achieved complete remission (CR) following chemotherapy and in CR1, a second HLA matched PBSCT from a different donor was offered. The patient is presently in remission at day +180 post-PBSCT. PMID- 27408398 TI - Avascular Necrosis of Head of Femur in Dyskeratosis Congenita - A Rare Presentation. AB - Avascular necrosis of head of femur is a rare presentation in Dyskeratosis Congenita (DC). Aplastic anaemia, increased susceptibility to infections and fatal pulmonary complications often complicate the clinical scenario in these patients leading to short life span and difficulty in performing surgical interventions. The diagnosis initially and subsequent management by total hip replacement posed a great challenge. To our knowledge this is the first case report of any intervention in form of total hip Arthroplasty done in DC. At 5 years of follow up the patient is asymptomatic with no radiographic signs of loosening or lysis. PMID- 27408399 TI - A Novel Mutation of Ribosomal Protein S19 Gene in a Chinese Child with Diamond Blackfan Anemia. PMID- 27408400 TI - Acquired Platelet Dysfunction with Eosinophilia (APDE) Syndrome: A Case Report. AB - Acquired platelet dysfunction with eosinophilia (APDE) is a syndrome which has transient state of platelet dysfunction in the presence of marked eosinophilia. This bleeding disorder, otherwise known as "non-thrombocytopenic purpura with eosinophilia", occurs commonly in children from South-East Asia. We report an 11 years old male child, who presented with ecchymotic patches over lower limbs, of recent onset. His hemogram revealed increased eosinophils with a normal platelet count. Coagulation screen revealed normal parameters except increase in bleeding time. Platelet aggregation studies showed normal platelet aggregation with ristocetin, reduced aggregation with ADP and no aggregation was seen with collagen. PMID- 27408401 TI - Dysfibrinogenemia with Subgaleal Hematoma: An Unusual Presentation. PMID- 27408402 TI - Pulmonary Hypertension and Pulmonary Aspergilloma-Coexistence of Two Rare Sequelae of Pulmonary Embolism. AB - We report a 42 year old non-smoker male who presented with progressive exertional dyspnoea, productive cough with streaky hemoptysis and progressive pedal edema. His physical examination, ECG, chest X-ray and 2D-ECHO revealed features suggestive of right heart failure and pulmonary hypertension. On further evaluation for the cause of pulmonary hypertension, his CT pulmonary angiography revealed features of chronic pulmonary thromboembolism with calcified thrombus in the main pulmonary artery along with pulmonary hypertension. Incidentally the CT also revealed a cavity in the right lung with soft tissue within it. A, trans thoracic needle aspiration of this tissue was suggestive of an aspergilloma. This is a rare case report of co-existence of two uncommon complications of pulmonary embolism-chronic thrombo-embolic pulmonary hypertension and pulmonary Aspergilloma in the same patient. PMID- 27408403 TI - Dasatinib and Dysfunction of Platelets. PMID- 27408404 TI - Co-existent Acquired Haemophilia and Lupus Anticoagulant. A Thorny Issue. PMID- 27408405 TI - Antiphospholipid Antibodies in Indian Women with Spontaneous, Recurrent Fetal Loss. PMID- 27408406 TI - Fatal Delayed Haemolytic Transfusion Reaction and Hyperhaemolysis Syndrome in a Pregnant Woman with Sickle Cell Anaemia. AB - Clinical manifestations of sickle cell disease (SCD) arise from the tendency of the sickle haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape. Sickle cell crisis is a devastating complication that may occur in patients with SCD. If not managed properly permanent organ damage and even death may be the final outcome. A case of a 32-year-old Nigerian lady, Gravida 1 Para 0 in her first trimester, with SCD who developed signs and symptoms of delayed haemolytic transfusion reaction after receiving packed red cell transfusion is demonstrated. Multiple red cell alloantibodies were detected in the patient's plasma; anti-Fy a, anti-Jk b and anti-E. The patient miscarriaged and succumbed to complications of hyperhaemolysis with delayed haemolytic transfusion reaction, acute chest syndrome and renal failure. There is an urgent need for mandatory red cell antibody screen and identification especially in high-risk cases. Prevention of alloimmunization by supplying phenotype-specific red cells is also required. PMID- 27408407 TI - Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis. AB - Hemoglobin Constant Spring [Hb CS; alpha142, Term->Gln (TAA>CAA IN alpha2)] is often missed by routine laboratory testing, especially in subjects with co inheritance of beta-thalassemia or beta-variants. We reported the case of a 1 year-old female with Hb H-CS disease who was born from a father with heterozygous of alpha-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [beta26 (B8) Glu->Lys, GAG>AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease. PMID- 27408408 TI - Sudden Death in Sickle Cell Anaemia: Report of Three Cases with Brief Review of Literature. AB - Vaso-occlusive crisis in sickle cell anaemia is one of the commonest presentations and a leading cause of death. Death can be sudden and unexpected. Herein we present three cases of sickle cell anaemia with sudden death within 3 days of hospitalisation. All the three cases presented with fever and jaundice. Two cases presented consecutively in the same year within a span of 5 months while the other case had presented 2 years prior to these two cases. Infection was the precipitating event in two cases and pregnancy with infection in one. One case in addition had 'right upper quadrant syndrome' and one case had 'acute chest syndrome' (ACS) due to bone marrow fat embolism. Postmortem liver biopsy of all the three cases showed dilated and congested sinusoids with sickled RBCs, kupfer cell prominence with erythrophagocytosis. Lung biopsy of case with ACS showed vessels occluded with bone marrow elements indicating bone marrow fat embolism. PMID- 27408409 TI - Secondary Sea-Blue Histiocytosis in a Patient with Transfusion Dependent HbE-Beta Thalassaemia and Osteosarcoma. AB - Secondary sea-blue histiocytosis occurs more frequently than the primary form and occurs consequent to a wide range of metabolic and haematologic disorders including thalassaemia. We report an 18-year-old Chinese boy with transfusion dependent HbE-beta thalassaemia who complained of pain and swelling at the left iliac crest region for 2 months duration. Physical examination revealed pallor with hepatosplenomegaly. Local examination revealed a huge swelling 12 cm * 12 cm in diameter, firm in consistency and tender. Histopathological examination of the mass revealed an osteosarcoma. His bone marrow aspirate showed numerous sea-blue histiocytes, the cytoplasm of which was closely packed with fine granules that stained blue with May-Grunwald-Giemsa. The nuclei were centrally located in some cells and displaced towards the periphery in other cells. There was no malignant cell infiltration in the marrow. The case is reported due to the co-incidental dual pathology in our patient (HbE-beta thalassaemia and osteosarcoma) and the unusual bone marrow finding of numerous sea-blue histiocytes. PMID- 27408410 TI - Detection of Co-inheritance of Hb Hope and Hb Constant Spring in Three Thai Samples by Capillary Electrophoresis. AB - The diagnosis of co-inheritance of Hb Hope [beta136(H14)Gly -> Asp, GGT > GAT] and Hb constant spring [Hb CS; alpha142, Term -> Gln (TAA > CAA IN alpha2)] by high performance liquid chromatography (HPLC) is difficult because Hb Hope has a HPLC elution pattern similar to that of Hb Pyrgos, Hb New York, Hb Kodaira, and Hb Phimai. Moreover, the Hb CS mRNA, as well as the gene product, are unstable and present at a low level in peripheral blood. We report the use of a capillary electrophoresis (CE) for diagnosis of co-inheritance of Hb Hope and Hb CS in 3 Thai females who had mild anemia with Hb and Hct varying from 91-114 g/L to 0.28 0.36 L/L, respectively. Hb Hope eluted with a retention time of 125-140 s (Zone 10) of CE electrophoregram. Furthermore, the peak of Hb CS at the retention time of 245-250 s (Zone 2) was observed in these samples. In addition, the manual analysis by taking the non-black area under both peaks of HbA and Hb Hope (inverted V) into account provided the corrected Hb CS levels which are useful in screening of heterozygote or homozygote for Hb CS. Thus, the CE method provides an accurate diagnosis of Hb Hope and Hb CS which is useful in genetic counseling, prevention and control programs for these hemoglobinopathies. PMID- 27408412 TI - New Codanin-1 Gene Mutations in a Italian Patient with Congenital Dyserythropoietic Anemia Type I and Heterozygous Beta-Thalassemia. AB - Congenital dyserythropoietic anemia type I is an autosomal recessive disorder associated with macrocytic anemia, ineffective erythropoiesis, iron overloading and characterized by abnormal chromatin ultrastructure in erythroblasts such as internuclear chromatin bridges, spongy heterochromatin and invagination of the nuclear membrane. A 58-year-old Causasian man with chronic hemolytic anemia, heterozygous for beta (+) -globin IVS1, nt110 G>A mutation (causing abnormal alpha:beta globin chain ratio) showed clinical, laboratory and hematological features suggesting diagnosis of CDA1. Sequence analysis of CDA-related genes revealed compound heterozygosity for two novel mutations in the CDAN1 gene: a frameshift mutation 3367 del 4 (TTAG) in exon 25 and a missense mutation c.1811 G>T in exon 11 causing an aminoacid change from glycine to valine at codon 565 (G565V). One of the propositus' brothers showed the same gene mutations. As the CDA1 can mimic thalassemia, a frequent misdiagnosis is possible especially in countries where the prevalence of thalassemia is high. A strong clinical suspicion in patients who do not reveal a clear genetic basis for presumed thalassemia may help clinch the correct diagnosis. PMID- 27408411 TI - Congenital Dyserythropoietic Anemia Type 1: Report of One Patient and Analysis of Previously Reported Patients Treated with Interferon Alpha. AB - Congenital dyserythropoietic anemias are a rare group of inherited anemias characterized by ineffective erythropoiesis and distinct morphological abnormalities in the erythroblasts. Interferon alpha has been shown to be effective in type 1 congenital dyserythropoietic anemia but the optimal duration of therapy is undefined. We present here a 32-years-old female patient diagnosed with type 1 congenital dyserythropoietic anemia precipitated by pregnancy and treated successfully with a short course of interferon alpha resulting in a durable response. A literature search including PubMed database on previously published articles regarding congenital dyserythropoietic anemia type 1 patients treated with interferon is conducted. PMID- 27408413 TI - Five Rare beta Globin Chain Hemoglobin Variants in India. AB - Thalassemias as well as structural hemoglobin (Hb) variants are common monogenic inherited disorders of Hb in India. In this paper we describe 5 rare beta-chain Hb variants identified in the Indian population on the basis of high performance liquid chromatography (HPLC). Of these 3 were identified during antenatal screening of beta-thalassemia while the other 2 cases were referred to us for a diagnostic work up. These 5 Hb variants were Hb British Columbia (beta CD 101 GAG -> AAG), Hb Saint Louis (beta CD28 CTG -> CAG), Hb G Coushatta (beta CD 22 GAA -> GCA), Hb Pyrgos (beta CD 83 GGC -> GAC) and Hb Agenogi (beta CD 90 GAG -> AAG). Hb Saint Louis and Hb G Coushatta eluted in the HbA2 window, Hb British Columbia and Hb Agenogi eluted in the Hb C window while Hb Pyrgos eluted in an unknown window on HPLC. They were all identified by DNA sequencing. The child having Hb St. Louis had hepatosplenomegaly and anemia while the individuals with the other 4 variants were asymptomatic. Rare Hb variants are diagnostic curiosities that may be encountered by laboratories. Correct identification requires the application of more than one technique to avoid misdiagnosing them as more common variants (e.g. St. Louis and G Coushatta as E or D Iran on HPLC. Some, like G Coushatta may interfere with HPLC-based HbA1c estimation). PMID- 27408414 TI - Delayed Serological Transfusion Reaction After Platelet Transfusion Due to Anti e. AB - Delayed serological transfusion reaction (DSTR) is defined as absence of clinical signs of hemolysis and demonstration of new, clinically-significant antibodies against red blood cells after a transfusion, by either positive direct antiglobulin test or positive antibody screen with newly identified RBC alloantibody. Various delayed hemolytic transfusion reaction cases are reported after red cell transfusions. However, the incidence of DSTR after platelet transfusion due to non-Rh(D) antibodies is not much documented. We report here a case of DSTR due to anti-e Rh antibody in a multiply red cell alloimmunized female patient after single donor platelets transfusion. PMID- 27408415 TI - Resolution of Serologic Problems Due to Cold Agglutinins in Chronic Lymphocytic Leukemia. AB - INTRODUCTION: Autoimmune hemolytic anemia can be classified depending on presence of warm, cold or mixed type of autoantibodies that are directed against antigens on the red blood cell surface. Here we report a case of pathological cold agglutinin disease which was eventually detected due to blood group discrepancy. CASE DETAILS: A request was sent to the blood bank for two units of packed red cells in a diagnosed case of CLL which showed type IV discrepancy during blood grouping.The discrepancy was subsequently resolved after warm saline washing of red cells along with repetition of reverse grouping with pre-warmed serum. The direct antiglobulin test was positive and revealed autoanibodies against C3b/C3d only. Indirect antiglobulin test was performed with 3-cell panel in a polyspecific gel card (IgG+C3d) showed a pan-reactive pattern along with a positive autocontrol. Subsequently a cold agglutinin titration was performed and titers of 1024 at 4 degrees C; titer of 2 at room temperature were detected. Dithiothreitol (DTT) treatment of serum was undertaken and IgM type of autoantibody was detected in this case confirming a case of secondary cold agglutinin disease in this patient. Two units of red cells were transfused to this patient after successfully performing cross-match with pre-warmed serum. It was advised from the blood bank that the blood should be transfused slowly through a blood-warmer and patient should be kept in warm condition to avoid in vivo hemolysis due to high titer of cold agglutinin. The transfusion was uneventful and patient is on regular follow-up till now. CONCLUSION: Thus we concluded that serological discrepancies observed in blood bank can successfully guide the bedside transfusion protocol in case of cold agglutinin disease. PMID- 27408416 TI - Hb D: A Not So Rare Hemoglobinopathy. PMID- 27408417 TI - Accidental Poisoning Resulting in Severe Methemoglobinemia in a 14-year-old Girl. PMID- 27408418 TI - Priapism Associated with Homozygous Hb E State: A Causal Association or an Incidental Finding? PMID- 27408419 TI - Reconfirming HPLC-Detected Abnormal Haemoglobins by a Second Independent Technique: A Judicious Approach. PMID- 27408420 TI - Significance of Adopting a Sensitive Technique for Donor Antibody Screening. PMID- 27408421 TI - Neutrophil Erythrocyte Rosettes: An Unusual Manifestation of Autoimmune Hemolytic Anemia. PMID- 27408422 TI - Hematological and Molecular Characterization of Hb J-Buda [alpha61(E10)Lys -> Asn, AAG > AAT]. AB - Hemoglobin (Hb) J-Buda [alpha61(E10)Lys -> Asn, AAG > AAT] is a very rare alpha chain variant found in South-East Asia. We analyzed hematological parameters and provided a rapid molecular analysis method for detection of this hemoglobinopathy in two Thai women who had severe microcytic anemia with Hb and MCV <70 g/L and 80 fL, respectively. The HPLC revealed an abnormal Hb peak eluted ahead of HbA at retention time of 1.91-1.98 min. On CE, the abnormal Hb peak was observed at the electrophoretic zone 12 which corresponded to Hb Bart's. The DNA sequencing revealed the AAG -> AAT mutation at codon 61 for Hb J-Buda on one allele of the alpha1-globin gene. The developed Allele-specific PCR (ASPCR) showed the 455 bp amplified fragment from Hb J-Buda allele. Thus, understanding of hematological characterizations and the developed ASPCR for diagnosis of Hb J-Buda are essential for genetic counseling of this hemoglobinopathy. PMID- 27408423 TI - A Novel A1088T Mutation in the Glucose-6-Phosphate Dehydrogenase Gene Detected by RT-PCR Combined with DNA Sequencing. AB - Human glucose-6-phosphate dehydrogenase deficiency (G6PD) is mostly caused by single nucleotide change in the G6PD gene which leads to single amino acid substitution. Previous trials suggested a few samples had decreased ratio of G6PD/6PGD(<1.00) but no mutation detected by multiple methods. In 138 cases of Chinese children with G6PD deficiency, RT-PCR combined with DNA Sequencing was performed to screen the mutations in the coding region and promoter region of G6PD gene. The mutation detection frequency by this method was 100 %, including a novel missense mutation (1088 A>T) and 13 mutations reported before. The novel mutation predicted an Asn-to-Ile substitution at codon 363, which was identified in a male infant patient. The variant caused by this mutation had reduced enzymatic activity, belonging to WHO Class I. Synonymous or missense mutation was not found in the proximal promoter region of the G6PD gene, which was consistent with earlier findings that G6PD deficiency was not associated with promoter mutations in the G6PD gene. RT-PCR combined with DNA Sequencing could be another alternative for clinically molecular diagnosis of G6PD deficiency. PMID- 27408424 TI - Middle East Respiratory Syndrome and Blood Donation: Topic for Further Study and Discussion. PMID- 27408425 TI - The Frequency of alpha-Globin Gene Triplication in a Southern Chinese Population. PMID- 27408426 TI - Prevalence and Viral Load of Human Parvovirus B19 (B19V) Among Blood Donors in South-East Brazil. AB - The infection of human parvovirus B19 (B19V) is a common event in the general population, including volunteer blood donors. In some cases it can be asymptomatic and can remain persistent for a long period of time. The objective of this study was to examine the B19V DNA prevalence and viral load in first-time volunteer blood donors. Blood samples were collected from 91 primary blood donors at the Regional Blood Center of Ribeirao Preto, Southeast Brazil. Viral detection and quantitation was performed by an in-house TaqMan((r)) real-time PCR with high sensitivity. B19V DNA was detected in one male blood donor (1.0 %) and was characterized by a very low viral load (537.36 copies/mL). Our studies demonstrate that B19V DNA at low titer may be present in apparently healthy individuals. Sensitive molecular diagnostic tools can be applied for the screening of fresh blood derived products in order to prevent transfusion transmitted B19V infection. PMID- 27408427 TI - Transfusion-Associated Graft-Versus-Host Disease with a Non-fatal Course. PMID- 27408428 TI - Misdiagnosis of Bone Metastasis Cancer After Using Adefovir Dipivoxi in a Hepatitis B Patient with Fanconi Syndrome. AB - Adefovir dipivoxil is commonly used for treatment of chronic hepatitis B patients. We present a case of acquired Fanconi syndrome and hypophosphatemic osteomalacia in a patient with chronic hepatitis B who had been treated with ADV for 8 years. A 41-year-old man complained of severe bilateral hypochondrium pain and lower limb weakness, and he had the diagnosis of bone metastasis cancer or multiple myeloma. Laboratory results and radiologic findings suggested Fanconi syndrome with osteomalacia after hospitalized. For it is difficult to accurately diagnose in clinic and prone to misdiagnose, more attention should be paid to the kidney damage in the patients treated with long-term ADV. PMID- 27408429 TI - Successful Management of Refractory Dialysis Independent Wegener's Granulomatosis with Combination of Therapeutic Plasma Exchange and Rituximab. AB - Wegeners granulomatosis (WG) is an autoimmune, antineutrophil cytoplasmic antibody mediated necrotizing vasculitis involving renal, and upper and lower respiratory systems. Treatment relies on a combination of immunosuppressive drugs and tapering regimen of glucocorticoids. Therapeutic plasma exchange (TPE) has been recognized as a second line treatment. We report the successful use of TPE in combination with rituximab in achieving remission in a patient with WG (dialysis independent) not responding to conventional therapy. PMID- 27408430 TI - Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease. AB - Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease. PMID- 27408431 TI - Hypereosinophilia in a Young Patient: Occam's Razor or Hickam's Dictum? AB - Hypereosinophilia is an uncommon clinical problem encountered in hematology practice. While most of such cases are secondary or reactive, a significant fraction of cases are due to clonal myeloproliferative disorders. We report a young patient who presented with marked hypereosinophilia and was investigated extensively for its cause. Finally a common tropical infection was responsible for such marked eosinophilia fulfilling the principle of Occam's razor. The case emphasizes the need to search for treatable reactive causes even in presence of marked hypereosinophilia in a tropical country. PMID- 27408432 TI - Familial Hemophagocytic Lymphohistiocytosis due to Mutation of UNC13D Gene. AB - Hemophagocytic lymphohistiocytosis (HLH) are basically a heterogenous group of clinical syndromes, characterised by activation and non-malignant proliferation of benign histiocytes i.e. lymphocytes and macrophages, leading to a cytokine storm that accounts for the fever, organomegaly and multi-organ dysfunction. Two types of HLH are described, either due to known genetic defect (familial HLH/FHL) or due to some acquired cause either infection or rheumatological diseases. Here we present a case of a 3 months old baby, admitted with fever, hepatosplenomegaly and cytopenia and ultimately was diagnosed to be a case of Familial HLH type 3 due to defect in UNC13D gene as a result of compound heterozygous for two nonsense mutation resulting in the Munc13-4 protein defect. PMID- 27408433 TI - Familial Pelger-Huet Anomaly. AB - Pelger-Huet anomaly is usually autosomal dominant, although it is likely that new mutations are common. This condition is characterized by granulocytes that are either bilobed or completely unsegmented. Here is a report of a 46 year old Indian lady who presented with fever to the hospital and on evaluation, her peripheral blood smear showed extreme hypolobation of granulocytes. Along with normal appearing neutrophils there were many neutrophils with bilobed and single monolobated nuclei which accounted for 82 % of the neutrophils. After identifying these neutrophilic abnormalities which were suggestive of Pelgeroid changes, the other family members were also screened and were found to be having similar morphologic abnormalities in granulocytes. As these changes were evident in granulocytic leucocytes of the patient as well as her mother, both her sisters and her son, with exception of her brother, the diagnosis of familial Pelger-Huet Anomaly was considered in this case. PMID- 27408434 TI - Hemophagocytic Lymphohistiocytosis Associated with Visceral Leishmaniasis: Varied Presentation. AB - Visceral leishmaniasis (VL) is endemic in many parts of India. Rarely, it may be complicated by hemophagocytic lymphohistiocytosis (HLH) that has varied presentation and course. We describe two cases of VL complicated by HLH that were markedly different in clinical presentation, course and management. First case presented with Fever of unknown origin whereas second case had fever with severe bleeding manifestations. VL was diagnosed by bone marrow aspiration and serum rk39 immunodiagnostic test respectively in these cases. HLH was diagnosed by HLH 2004 diagnostic criteria. VL was treated by intravenous amphotericin B in both cases. HLH was managed by treating primary disease in the first case whereas steroid was given for management in the second case. High index of suspicion is crucial for early diagnosis of HLH to reduce morbidity and mortality. PMID- 27408435 TI - Lymphocytic Platelet Satellitism. PMID- 27408436 TI - Anemia and Thrombocytopenia in New H5N6 Influenza: Existed or not? PMID- 27408437 TI - Gelatinous Transformation of Bone Marrow: A Prospective Tertiary Center Study, Indicating Varying Trends in Epidemiology and Pathogenesis. AB - Gelatinous bone marrow transformation (GTBM) also known as serous atrophy is a degenerative change in the hematopoietic bone marrow and is a rare well recognized pathological entity. It was earlier described mainly in association with anorexia nervosa and psychiatric eating disorders, but recently it has been reported in ulcerative colitis, tuberculosis, chronic renal diseases, immuno suppressed states (mainly HIV infection), malignancies and Kala azar. Treatment is based on treating the underlying disease. Our objective was to study the epidemiology and pathogenesis of diseases causing gelatinous transformation of bone marrow, at a tertiary center level. A prospective study was conducted on 732 samples of bone marrow aspirate with the aim of identifying gelatinous transformation in bone marrow aspirates which was confirmed by Alcian blue stain at pH 2.5. The presence of this material was correlated with the hematological profile of the patient, the presenting signs and symptoms and provisional clinical diagnosis at initial visit. Incidence of gelatinous transformation was calculated to be nearly 4.8 % and the condition was more common in males (23) as compared to females (12) (Male:Female = 2:1). Forty percent of the cases were seen in children followed by 37 % in adolescents and young adults. The older individuals comprised only 23 % of the cases. The bone marrow was hypocellular in 21 (60 %), normocellular in 10 (28.5 %) and hypercellular in four cases (11.5 %). Five cases with GTBM progressed to aplastic anaemia of which three were in children. PMID- 27408438 TI - Shoulder Myeloid Sarcoma: An Initial Presentation of CML Blast Crisis. AB - Myeloid sarcoma (MS) represents extra medullary accumulation of the immature cells of granulocytic series and occurs most commonly in the setting of acute myelogenous leukemia. Its occurrence in chronic myeloid leukemia (CML), myelodysplastic syndrome and other myeloproliferative neoplasm is uncommon. We here in report a 35-year old lady who was diagnosed as CML-chronic phase (CP) in the year 2004 and was on imatinib (400 mg OD) since then with regular follow up and good compliance. She had progression to accelerated phase in April 2014 which was managed by increasing the dose of imatinib to 600 mg OD. In August 2015, she presented with complaints of pain and swelling of the left shoulder suggestive of septic arthritis. Investigations revealed an ill-defined lesion involving muscles around the shoulder and clavicle. Absence of response to antibiotics and negative work up for infectious etiology raised the suspicion for MS which was later confirmed by immunohistochemistry of the aspirate from the lesion. Bone marrow examination was consistent with CML-CP. Hence, the diagnosis of CML with extra medullary blast crises was made. Patient was treated with a combination of high dose imatinib, hydroxyurea, cytarabine and local radiotherapy. Rarity of MS involving the shoulder and it's resemblance to septic arthritis has been highlighted in the present case. We emphasize the importance of immunohistochemistry of the aspirate for the timely and correct diagnosis of the cases who do not respond to an initial antibiotic trial. PMID- 27408439 TI - "Red Hand Syndrome" Due to Cytarabine in a Case of Mantle Cell Lymphoma. PMID- 27408440 TI - Isolated Intravascular Large B-cell Lymphoma Presenting with Diffuse Ground Glass Pulmonary Infiltrates. AB - A case of 44-year-old man with dyspnea and CT chest demonstrated bilateral infiltration. Patient was failed to improve with antibiotics and steroid. Finally, video-assisted thoracic surgery-guided lung biopsy was performed and surprisingly revealed intravascular large B cell lymphoma. The patient was subsequently started on chemotherapy with considerable clinical improvement. At the time of last follow-up (4 years from diagnosis); there was no clinical or radiologic evidence of tumor recurrence. PMID- 27408441 TI - Bullae And Blisters: A Rare Case of Bendamustine Skin Toxicity. PMID- 27408442 TI - Kaposiform Hemangioendothelioma in a 3 Months Old Infant. AB - Kaposiform hemangioendothelioma is a rare, highly vascular and aggressive soft tissue tumor frequently associated with Kasabach-Merritt phenomenon, usually seen in early infancy. Early diagnosis by means of MRI and tissue biopsy portends a better outcome. Treatment includes surgical excision when feasible and medical management with steroids, propranolol, vincristine and supportive treatment for coagulopathy. We report a 3 months old female infant who was diagnosed, treated successfully and is now in complete remission. PMID- 27408443 TI - Solitary Extramedullary Plasmacytoma of the Maxillary Sinus, Progressing to Smoldering Multiple Myeloma with Multifocal Skeletal Involvement, which Resolved Completely Following Chemotherapy Alone. AB - Plasmacytoma is an uncommon malignant tumor originating either from plasma cells located in the bone marrow also known as the solitary bone plasmacytoma, or from plasma cells located outside the bone, for e.g. in mucosal surfaces, referred to as the extramedullary plasmacytoma also called the solitary extramedullary plasmacytoma. Both, solitary as well as extramedullary bone plasmacytomas may, particularly in later stages, be accompanied by other osteolytic bone lesions (multifocal bone involvement) and features such as anemia, hypercalcemia, or renal impairment attributable to and indicative of progression to multiple myeloma. These three distinct disorders together comprise the plasma cell neoplasms and essentially represent a continuum of related disease processes. Extramedullary and solitary bone plasmacytomas of the head and neck region are extremely uncommon, and amongst them plasmacytoma of the maxilla is extremely rare. Such a case is being reported here for its rarity. Also, it was associated with multifocal skeletal involvement, making a correct categorization difficult as well as imperative in order to institute the correct treatment. Radiotherapy is considered to be the treatment of choice of plasmacytoma, with adjuvant chemotherapy for multi focal involvement. Surgery is usually limited to biopsy and excision of any residual disease following radiotherapy. The case presented responded extremely well to chemotherapy alone, with a complete resolution of the maxillary tumor, obviating the need for radiotherapy. PMID- 27408444 TI - Solitary Cysticercosis of the Temporalis Muscle: Report of a Rare Case. AB - Patient presented with swelling over right temporal region causing the dilemma over diagnosis. Sonography and CT scan confirmed the presence of cysticercus in right temporal region. Pharmacological management was instituted and the cyst resolved eventually. Ultrasonography and CT imaging play an important role in establishing the diagnosis of rare case of cysticercosis of temporalis muscle and can be treated successfully by pharmacological modality. PMID- 27408445 TI - Malignant Solitary Fibrous Tumor of the Scalp. AB - Solitary fibrous tumors are an uncommon slow growing benign neoplasm originally described as a pleural neoplasm but can also be found in the lung, mediastinum, peritoneum, or any other sites including the head and neck. Malignant solitary fibrous tumors (MSFT) are extremely rare and only few cases have been published in the literature. There have been 19 cases reported of MSFT in the head and neck, but there are no reports of MSFT located within the scalp in the English language literature. We present a case of MSFT arising in the scalp and describe our experience with the clinical presentation, surgical management, and outcome in this pathological condition. PMID- 27408446 TI - Hyoid Bone Fracture: Associated With Head and Neck Trauma-A Rare Case Report. AB - Fractures of hyoid bone resulting from trauma other than strangulation are very rare; hyoid bone fracture associated with panfacial trauma are even rarer. They occur more frequently in young individuals, and in men more than in women [1]. We report a comprehensive review of a case of hyoid bone fracture associated with head and neck trauma, induced by a direct blunt trauma onto the anterior neck. PMID- 27408447 TI - Slow-Growing Large Irritation Fibroma of the Anterior Hard Palate: A Case Report Using Immunohistochemical Analysis. AB - Irritation fibromas are recognized as fibrous lesions, usually reactive hyperplasias; however, the mechanism of enlargement is unclear. This paper reports on an abnormally large irritation fibroma of extremely gradual growth. The immunohistochemical features (CD34, alpha-SMA, vimentin, Ki-67, and TGF alpha) of this irritation fibroma are presented to distinguish reactive hyperplasia from other true fibrous neoplasm diseases. In the only previous study, it was reported that the expression of TGF-alpha might be associated with the development of oral fibromas. Therefore, we investigated the relationship between this exceptionally-large fibrous lesion of extremely slow growth and the immunohistochemical reactivity of TGF-alpha, finding that, in contrast to the previous study, TGF-alpha was not expressed. This is the first study to evaluate the enlargement mechanism of such a large irritation fibroma using the approach of immunohistochemical analysis, and it indicates that such analysis can help elucidate the diverse causes and enlargement mechanisms of irritation fibromas. PMID- 27408448 TI - Respiratory Distress Secondary to Rhabdomyosarcoma of the Tongue and Co-existent Choanal Atresia. AB - Whilst rhabdomyosarcoma (RMS) is the third most common solid tumour in children, congenital RMS of the tongue is extremely rare and usually present as painless progressive mass since birth (Dagher and Helman in Oncologist 4:34-44, 1999; Childs and Goudy in Int J Pediatr Otorhinolaryngol 5:126-128, 2010). In neonates, presentation with respiratory distress is unexpected as neonates are preferential nasal breathers and restricted oral breathing due to tumour usually poses no problem. We herein report a case of rhabdomyosarcoma of the tongue with co existent unilateral choanal atresia, presenting with respiratory distress. The baby developed upper respiratory tract infection following which developed severe respiratory distress. Airway symptoms were precipitated as there was combined obstruction of both the nostrils due to infection or adenoid enlargement and unilateral chonal atresia. Treatment of respiratory distress in the presence of RMS and bilateral nasal pathology must first prioritise the security of the airway, before taking a multi-factorial approach to the therapy of the lingual mass (Childs and Goudy in Int J Pediatr Otorhinolaryngol 5:126-128, 2010). This case illustrates the importance of vigilance with respect to co-existent nasal pathology, in order to avoid the occurrence of complete airway obstruction. We therefore feel that any diagnosis of lingual RMS should warrant a formal examination of both nasal cavities. PMID- 27408449 TI - Benign Spindle Cell Tumour of Mandible and Points of Modification in Reconstruction with Nonvascularised Iliac Crest Graft. AB - Benign fibrous histiocytoma (BFH) is a rare spindle cell tumor occurring in the jaw. It is a benign lesion composed of spindle shaped fibroblasts arranged in a storiform pattern. Literature shows that there are less than hundred reported cases of BFH worldwide and only six reported cases in the mandible. In this article, we are reporting a rare case of BFH in mandible and novel points of modification in reconstruction with nonvascularised iliac crest graft . PMID- 27408450 TI - Metastatic Follicular Carcinoma Thyroid Masquerading as a Primary Jaw Tumor. AB - Metastatic tumours of the oral cavity are rare constituting approximately one percent of all oral malignancies. These tumors are clinically significant as their appearance may be the first indication of an undiscovered malignancy at a distant primary site or the first evidence of dissemination from a known primary tumor. Thyroid cancer metastasizing to the jaw bones is a rare occurrence and very few cases have been described in literature. We present an additional case which in fact masqueraded as a primary jaw tumor. Metastasis to jaw bones is generally associated with poor prognosis with a majority of the patients dying within 6 months of diagnosis. Thyroid cancers however seem to be an exception to this, resectable solitary jaw bone metastasis from differentiated thyroid cancers is associated with a much better prognosis and therefore should be considered for metastatectomy. PMID- 27408451 TI - Immediate, Non Submerged Root Analog Zirconia Implant in Single Rooted Tooth Replacement: Case Report with 2 years Follow Up. AB - This report demonstrates the clinical use of a modified, truly anatomic, root analogue zirconia implant for immediate replacement of a right mandibular first premolar. A 22-year-old female patient with chronic apical periodontitis of the right mandibular first premolar was referred and the tooth was carefully extracted. A truly anatomical, root identical, roughened zirconia implant modified by macro-retentions was manufactured and placed into the extraction socket by tapping 3 days later. After 4 months a composite crown was cemented in place. No complications occurred during the healing period. A good functional and aesthetic result was achieved with minimal bone resorption and soft tissue recession at 18 months follow-up. This report describes the successful clinical use of an immediate, single stage, truly anatomical root-analogue zirconia implant for replacement of a single rooted tooth. Significant modifications such as macro-retentions yielded primary stability and excellent osseointegration. This novel approach is minimally invasive, respects the underlying anatomy and aids socket prevention. In addition the procedure saves time and cost, has good patient acceptance as there is no need for osteotomy, sinus lift or bone augmentation. PMID- 27408453 TI - The Meningioma that Got Cheeky. AB - Extracranial meningiomas are rare with a reported incidence of 1-2 %. Diagnosis is a challenge due to the unusual site of occurrence. The treatment of choice is surgical excision. A case that presented with primary lesion in the cheek with no detected intracranial extension is being reported. PMID- 27408452 TI - Temporal Space Lymphatic Malformation in a 15-Year-Old Adolescent: An Extraordinary Case. AB - Lymphatic malformations-previously called lymphangiomas or cystic hygromas-are regarded as non-malignant primary disorders of the lymphatic system. They appear predominantly in infants and children, with 90 % of cases being diagnosed by the age of 2 years. Also, they constitute an infrequent entity, accounting for 5 % of all benign tumors in infants and children. In adults they are extremely rare. In the present article we present an extraordinary case of a lymphatic malformation that ensued in the temporal area of a 15-year old adolescent. PMID- 27408454 TI - Subcutaneous Benign Fibrous Histiocytoma: Rare Presentation on Cheek-Case Report and Review of Literature. AB - Fibrous histiocytoma is a benign tumor of mesenchymal origin. The tumor frequently appears in sun exposed areas on skin and orbital tissues. The subcutaneous appearance of this tumor in deep soft tissues is rare. We present here the eighth reported case of subcutaneous benign fibrohistiocytoma in a 27 year old male patient. Histopathology of the tumor comprises fibroblastic and histiocytic cells which mimic dermatofibroma, xanthomas and nodular fasciitis. Special stains like vimentin can only differentiate these tumors. PMID- 27408455 TI - Primary Gingival Melanoma: An Important Entity. AB - Primary melanoma of the mandibular gingiva is extremely rare. It is often misinterpreted as a benign pigmented process. The prognosis of this entity is very poor. We report here the first case of primary gingival melanoma described in the Tunisian literature about a 55-year-old smoker having cerebral and pulmonary metastases from gingival melanoma at diagnosis. Our patient underwent brain radiotherapy at a dose of 18 Gy in three sessions but he died with a decline of 3 months before starting systemic therapy. Therefore, each new case should be illustrated to make clinicians aware about the importance of the early diagnosis to improve the poor diagnosis of this entity. PMID- 27408456 TI - An Extremely Rare Case of Accessory Auricle, Polyotia and its Surgical Correction. AB - Certain malformations may occur during the embryonic development of the ear. Accessory auricle has a wide range from a small elevation of skin to a large size to resemble an additional auricle, where the latter is called polyotia. This condition is defined as an accessory auricle that is large enough to closely resemble an additional pinna rather than a skin remnant and cartilage. Polyotia, also known as mirror ear or accessory ear, is a type of ear anomaly in the tragus area, but this term refers to substantial anomalies which resemble an accessory ear, unlike a pre-auricular tag. Here, we present a case of an accessory auricle in a young female adult. The occurrence was unilateral; the subject did not have any audiological disorder. A simple surgical procedure is also mentioned for excision of accessory without any complications. We compared our findings with different cases of accessory auricle in the literature. The clinical importance and genetic association are also discussed. PMID- 27408458 TI - An Unusual Observation During Neck Dissection. AB - External jugular vein (EJV) is a major superficial vein in the neck which drains deeper parts of face and posterior scalp region. Although it follows a predicted pattern in formation, course and termination in general unusually it also exhibits variations which are clinically important. Gross variations in the incidence of these variations in EJV are noted. We report an anomalous course of EJV which drains into internal jugular vein in our case report. Knowledge about EJV and its origin, course and termination is important for surgeons, interventional radiologist, anaesthesiologist, clinicians in general to avoid inadvertent complication. PMID- 27408457 TI - Regeneration of a Compromized Masticatory Unit in a Large Mandibular Defect Caused by a Huge Solitary Bone Cyst: A Case Report and Review of the Regenerative Literature. AB - The reconstructive options for large expansive cystic lesion affecting the jaws are many. The first stage of treatment may involve enucleation or marsupialization of the cyst. Attempted reconstruction of large osseous defects arising from the destruction of local tissue can present formidable challenges. The literature reports the use of bone grafts, free tissue transfer, bone morphogenic protein and reconstruction plates to assist in the healing and rehabilitation process. The management of huge mandibular cysts needs to take into account the preservation of existing intact structures, removal of the pathology and the reconstructive objectives which focus both on aesthetic and functional rehabilitation. The planning and execution of such treatment requires not only the compliance of the patient and family but also their assent as customers with a voice in determining their surgical destiny. The authors would like to report a unique case of a huge solitary bone cyst that had reduced the ramus, angle and part of the body of one side of the mandible to a pencil-thin like strut of bone. A combination of decompression through marsupialization, serial packing, and the fabrication of a custom made obturator facilitated the regeneration of the myo-osseous components of the masticatory unit of this patient. Serial CT scans showed evidence of concurrent periosteal and endosteal bone formation and, quite elegantly, the regeneration of the first branchial arch components of the right myo-osseous masticatory complex. The microenvironmental factors that may have favored regeneration of these complex structures are discussed. PMID- 27408459 TI - Superolateral Dislocation of Intact Mandibular Condyle: A Case Report and Review of Literature. AB - Anteromedial fracture dislocation of the mandibular condyle is common but a superolateral dislocation of an intact condyle is quite rare. This type of dislocation is often misdiagnosed or completely overlooked and hence inadequately addressed. We report a case of a 41-year-old male patient who experienced superolateral dislocation of the intact condyle with symphysis fracture and panfacial fracture following a road-traffic accident, and review of literature of superolateral dislocations from 1967 to 2014. PMID- 27408460 TI - Orthokeratinized Odontogenic Cyst (OOC) of Condylar Head: A Rare Entity. AB - Orthokeratinized odontogenic cyst (OOC) is a rare developmental jaw cyst, considered as distinct entity from odontogenic keratocysts as it exhibits a less aggressive behaviour and a very low rate of recurrence. Most commonly occurs in mandibular molar and ramus region, rarely seen in maxilla and mandibular premolar area. But till now never reported in condyle, this article describes a case of OOC involving the mandibular condylar head in a 41-year-old male. The initial clinical diagnosis was given as TMD based on the clinical features, but radiographic evaluation revealed osteolytic lesion in right side condylar head. Condylotomy was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. We report a rare entity in this article with its management. PMID- 27408461 TI - An Erupted Silent Tumour. AB - Odontomas are the most common odontogenic tumors of the oral cavity which are nonaggressive, hamartomatous in nature consisting of enamel, dentin and cementum. They are called as composite because they contain more than one type of tissue. They are generally asymptomatic, hence recognised on routine radiologic examination. The compound odontoma is composed of multiple small tooth like structures, whereas the complex odontoma consists of a conglomerate mass of enamel and dentine, which bears no anatomical similarity to the tooth. The eruption and infection of odontoma are uncommon, only few cases of erupted complex odontoma are reported in the literature. We report a case of silent erupting complex odontoma. PMID- 27408462 TI - High Palatoglossal Arch: A New Indication for Pre-prosthetic Surgery. AB - Pre-prosthetic surgery helps to overcome the challenge of prosthetic rehabilitation of the patient including restoration of the best masticatory function possible, combined with restoration or improvement of dental and facial esthetics. Maxillary denture prosthesis fabrication should include thorough examination of the soft palate and palatoglossal arch anatomy. This case report emphasizes on high palatoglossal arch as a rare and new cause of loss of posterior palatal seal and thereby retention of maxillary denture with rational, treated by pre-prosthetic surgery, ever reported in literature. PMID- 27408463 TI - Nodular Fasciitis of the Orofacial Region: An Uncommon Differential. AB - Nodular fasciitis is a benign proliferative spindle-cell lesion that presents as a rapidly growing mass arising from the subcutaneous fascia, leading it to be erroneously diagnosed as a sarcoma. These lesions commonly present in individuals in their third to fifth decades of life with no definite gender predilection. They are frequently located on the extremities and the trunk and infrequently in the head and neck region. Lesions in the orofacial region are uncommon. We describe an interesting case of orofacial nodular fasciitis in a 21-year-old boy that essentially summarises the clinical features and management of this pseudosarcomatous reactive proliferative lesion. Clinicians and more so maxillofacial surgeons need to be aware of the distinctions between nodular fasciitis and its malignant mimic (sarcomas) in order to limit overtreatment and the resultant treatment-related morbidities. PMID- 27408464 TI - Simple Correction of the Congenital Cleft Earlobe. AB - The appearance of the ear is an important component of the facial characteristics. Lower auricular malformations are less frequent than total or upper auricular malformations. The patients are affected unilaterally in general. Cleft earlobe is frequently encountered among earlobe anomalies. The presented case may be classified as longitudinal type according to Kitayama (Jpn J Plast Reconstr Surg 11:663-670, 1980). Many of the correction methods may lead to patient discomfort due to possible conspicuous scar. The patient was a 5 year old girl. In the presented case, a simple method has been performed. Satisfactory outcome is achieved. As a simple method applying longitudinal division and rotation procedure does not have marginal excision. Furthermore there is no additional incision outside the cleft margin. Local flap and graft are not applied. Conservative approach was maintained with respect to scar occurrence. This method is not favourable in the case of acquired split earlobe deformities due to the wide cleft surface. Postoperative 3rd-month appearance demonstrated adequate correction. PMID- 27408465 TI - Case Report: Gorham-Stoute Syndrome with Involvement of Majority of Mandible, and Partial Maxillary, Temporal and Zygomatic Bones. AB - The Gorham-Stout syndrome is a rare condition in which spontaneous, progressive resorption of bone occurs. The diagnosis is based on clinical, radiological and histopathological findings after excluding other etiologies and as a result it is often delayed. We present the case of a 21-year-old male diagnosed with Gorham Stout syndrome with involvement of the majority of the mandible, partial involvement of right maxillary, temporal and zygomatic bones and discuss its diagnostic and therapeutic features. PMID- 27408466 TI - Dermoid Cyst of Submental Region Mimicking Pilomatricoma. AB - Diagnosis of midline neck swellings may give a myriad of options, ranging from ranula, thyroglossal duct cyst, cystic hygroma, cystic lymphangioma, epidermoid, dermoid and teratoid cysts to benign or malignant neoplasms of the mucosa or salivary glands and also rare skin appendage tumours like pilomatricoma or pilomatrix carcinoma. Various pitfalls are encountered in diagnosing these midline swellings as most of the features are overlapping. Careful history and examination have to be complemented with other diagnostic aids such as conventional radiography, ultrasonography, aspiration cytology and computed tomography to arrive at a correct diagnosis. Dermoid cysts in the head and neck are relatively uncommon, present in the midline either above or below the mylohyoid muscle thus differentiating it into sublingual and submental dermoids and can grow to a massive size before presenting symptoms if it breaches the mylohyoid muscle. Pilomatricoma is a skin appendage tumour which presents as midline swelling and is usually diagnosed with careful history and certain pathagnomonic features on fine needle aspiration cytology and ultrasonography. Hereby we are presenting a case of a submental swelling which was diagnosed as a dermoid cyst upon excision but which initially posed a diagnostic challenge because of features of pilomatricoma seen on FNAC. PMID- 27408467 TI - Pituitary Adenoma Leads to Adenoid Cystic Carcinoma in the Oral Cavity: An Intriguing Case. AB - Adenoid cystic carcinoma is a tumor of the exocrine glands originating primarily from the minor salivary glands. Though rare but there has been incidences of its spread into intracranial sites via different routes. We report of an intriguing case of remote metastasis of intracranial tumor in the pituitary diagnosed as pituitary adenoma which spread to the oral cavity as adenoid cystic carcinoma. To our knowledge, this is the first reported case of seeding of cells from intra cranial pituitary adenoma to intra-oral site manifesting as adenoid cystic carcinoma. PMID- 27408468 TI - Extranodal Marginal Zone Lymphoma of the Parotid Gland. AB - Non Hodgkin lymphomas correspond to 25 % of all head and neck cancers. These rare tumors only include less than 5 % of malign tumors in parotid region. Differential diagnosis of these tumors cover many malign and benign tumors of the parotid gland. Definite diagnosis depends on sufficient tissue material of parotidectomy specimen. Treatment modality is surgical removal of the lesion with or without additional radiation and chemotherapy depending on the stage of the tumor. Prognosis is better than other forms of the B-cell lymphoma. We present a 54 year old woman who suffered from progressively and slowly growing mass on parotid region, without any inflammatory disease or chronic infection, diagnosed with mucosa associated lymphoid tissue lymphoma of the parotid gland. Parotid gland was totally excised by superficial parotidectomy and there is no recurrence after 5 years postoperative period. PMID- 27408469 TI - Benign Paroxysmal Positional Vertigo Following Sinus Floor Elevation in Patient with Antecedents of Vertigo. AB - Benign paroxysmal positional vertigo (BPPV) is an unfamiliar and rare complication occurring following osteotome sinus floor elevation (OSFE) and simultaneous implant placement. Etiology of this disorder is commonly displacement of otoliths by vibratory forces transmitted by osteotomes and mallet along with the hyperextension of the head during the operation, causing them to float around in the endolymph. This report presents a case of protracted BPPV following OSFE and simultaneous implant placement. A 43-year-old female suffered intense vertigo and nausea immediately after implant placement using an OSFE procedure. Upon further questioning after the procedure she gave an account of two times vertigo history within the last 9 years. Despite nootropic drug medication and canalith repositioning procedure applied by a specialist at operation night, the condition did not improve. Patient did not totally recover and was admitted again after 1 month. After repeated maneuvers, nine dosage intravenous serous fluid and piracetam administration the patient recovered. Duration of these procedures took 10 days and the patient was successfully treated with no recurrence of dizziness. Prevention and management of OSFE related BPPV are reviewed especially in patients having prior vertigo history in this report. PMID- 27408470 TI - Conversion of Aneurysmal Bone Cyst into Fibrous Dysplasia: A Rare Pediatric Case Report. AB - Aneurysmal bone cyst (ABC) is an uncommon, non-neoplastic, expansive and erosive bone lesion. Considered as a pseudocyst due the lack of epithelial lining, the presence of giant cells and similarity to other lesions can make preoperative diagnosis difficult; biopsy findings must be co-related to complete clinical and radiological assessment. ABC's controversial etiopathogenesis and variable clinicopathological presentations have been widely described, but to date, there are just a few reports in literature describing the development of fibrous dysplasia (FD) from an ABC, and even less cases occurring in the jaws. We describe the case of an ABC in an 8 year-old male patient, affecting the body of the mandible, which showed accelerated growth associated to thinning of the buccal, lingual and lower cortical plates. The treatment consisted of repetitive surgical resection, curettage of the lesion and mandibular reinforcement with osteosynthesis reconstruction plates. A 16-month follow-up showed self-limitation of the overgrowth. The final histopathological and radiological analysis confirmed the FD diagnosis. PMID- 27408471 TI - A Conservative Surgical Approach in the Management of Longstanding Chronic Protracted Temporomandibular Joint Dislocation: A Case Report and Review of Literature. AB - Chronic protracted dislocation of the TMJ is a relatively uncommon but extremely unpleasant and distressing condition for a patient. It is also particularly challenging and difficult to treat as it worsens with time due to continuing spasm of the masticatory muscles and progressive fibrosis, adhesions and consolidation in and around the dislocated joint. No definite guidelines or treatment protocols have been laid down in literature till date, towards management of such dislocations. A range of extensive and invasive surgical procedures such as eminectomy, condylectomy, menisectomy, and various osteotomies of the mandibular ramus and body have been performed to reduce these dislocations. A chronic longstanding unilateral TMJ dislocation in a 64-year-old woman was managed successfully and effectively using a modified, rather conservative surgical technique. The aim was to reduce the dislocated condyle (without excessive manipulation of the intra-articular space or extra-articular joint components); and at the same time, to limit further excessive translation of the condyle and restore physiological TMJ biomechanical constraints, to prevent future recurrence. This was achieved by surgically exposing the dislocated joint and manipulating the anterosuperiorly positioned condyle back into the glenoid fossa, aided by a downward distraction of the mandible; followed by soft tissue tethering of the meniscus and fibrous capsule of the joint to the temporal fascia above. The procedure yielded excellent results without any functional limitations or recurrence, and can hence constitute a viable and effective treatment option which can be attempted prior to resorting to the more invasive surgical procedures as described in literature. PMID- 27408472 TI - Intraoral Superficial Angiomyxoma: A Case Report. AB - Angiomyxomas are a group of relatively uncommon myxoid mesenchymal tumors associated with a high risk of local recurrence without any metastatic potential. Till date only five cases of intraoral superficial angiomyxoma have been reported. This is a case report of a middle aged Indian male patient diagnosed with superficial angiomyxoma of lower left buccal vestibule. PMID- 27408473 TI - A Rare Case of Multiloculated Cervical Thymic Cyst Masquerading as Tuberculous Adenitis. AB - Cervical thymic cysts are among the rarest cysts found in the neck. They usually occur during infancy and childhood, and they are extremely rare in adults. They may be found at any level of the pathway of normal thymic descent, from the angle of the mandible to the superior mediastinum. Being uncommon, they are rarely included in the clinical diagnosis of lateral neck masses and are commonly misdiagnosed as branchial cysts, lymphatic malformations, epidermoid cysts, dermoid cysts, lymphadenitis or neoplastic masses. The diagnosis of cervical thymic cyst is rarely made preoperatively and histopathological examination of the excised specimen is the only definitive means of diagnosis in a majority of the reported cases. We report the clinical presentation and therapeutic management of a rare case of multiloculated cervical thymic cyst in a 24-year-old adult which masqueraded as a tuberculous lympadenitis along with a review of literature. PMID- 27408474 TI - A Rare Case of a Recurrent Giant Solitary Fibrous Tumor of the Ciliary Body of the Orbit. AB - Solitary fibrous tumors (SFTs) are uncommon spindle-cell tumors of mesenchymal origin initially described in the pleura and subsequently in other extra-pleural sites. These tumors are categorized as tumors of 'intermediate malignancy' under the World Health Organization classification of soft tissue tumors. SFT was virtually non-existent or misdiagnosed until its characteristic features, particularly the strong and diffuse immuno-reactivity to CD 34 were described. Extra-pleural manifestations of SFT, particularly in the head and neck region are rare. Although a number of isolated case reports of orbital SFTs have been described ever since its initial description in 1994, cases of recurrent SFTs have been very few. Recurrences of these tumors following surgery are considered unusual and metastasis exceptional. We describe clinical presentation and the management challenges of recurrent giant orbital SFT in a 15-year old girl along with a brief review of literature. PMID- 27408475 TI - Congenital Hypertonia of the Temporalis Leading to Trismus Since Birth. AB - Congenital trismus is quite rare especially when its etiology is not the usual. In our case report an 8 year old female patient with no history of forcep delivery, no history of trauma or infection and a non syndromic presents with trismus since birth. After thorough examination we could conclude that the cause is due to hypertonia of the temporalis muscle and its etiology is discussed. PMID- 27408476 TI - Outcomes following the treatment of bicondylar tibial plateau fractures with fine wire circular frame external fixation compared to open reduction and internal fixation: A systematic review. AB - PURPOSE: The aim of this study was to determine whether circular frame external fixation provides better outcome and fewer complications when compared to open reduction internal fixation. METHODS: A systematic search was carried out and studies were critically appraised with narrative data synthesis. RESULTS: The systematic search yielded 131 titles and following a rigorous review only five articles were found to directly compare the two treatment methods. CONCLUSIONS: Fine wire frame external fixation offers a modest advantage of better soft tissue outcomes. All in all, there is no current high-level evidence to suggest that newer osteosynthesis plates provide better results. PMID- 27408477 TI - Schwannoma of the digital nerve and reconstruction with reverse-flow dorsal metacarpal artery flap: A case report. PMID- 27408478 TI - Stress fracture of the ulna in a softball pitcher. AB - BACKGROUND/AIMS: We present a rare case of stress fracture of the diaphysis of the ulna in a softball pitcher. CASE: A thirteen-year-old girl felt pain over the distal third of the right forearm during pitching. Stress fracture was detected as callus formation of the ulna before fracture displacement. When windmill pitching for softball, the pitcher rotates their arm around the shoulder joint and powerfully hits their forearm to their thigh, which is accompanied by simultaneous pronation of the forearm and flexion of the wrist. The ball is then released and this movement is known as "brushing". CONCLUSIONS: The typical throwing form in a softball pitcher can play an important role in stress fractures of the ulna. PMID- 27408479 TI - Osteotomy for deformities in blount disease: A systematic review. PMID- 27408481 TI - The effects of a semi-rigid soled shoe compared to walking barefoot on knee adduction moment. AB - BACKGROUND/PURPOSE: On a background of literature suggesting that certain rigid soled shoes may increase the knee adduction moment during gait this study was performed to look at specific postoperative shoe - the Medishoe. This shoe is used on a daily basis in a district general hospital orthopaedic department for patients post-operatively to protect wounds and fixations. METHODS: Using force plates and an opto-electronic motion capture system with retroreflective markers the knee adduction moment was estimated in ten healthy subject both with and without the shoe during normal gait. The angle at which the ground reaction acted with respect to the ground in the coronal plane as well as the tibiofemoral angle were also calculated using the Qualsys software - both with and without the Medishoe. RESULTS: Two-tailed paired t-tests using a 95% confidence interval showed that there was no significant difference between the two groups in the estimated knee adduction moment (p = 0.238), tibiofemoral angle (p = 0.4952) and the angle of the ground reaction force to the ground (p = 0.059). CONCLUSION: There was no significant difference in the estimated knee adduction moment between the two groups, although there was a statistical trend to an alteration in the angle of the ground reaction force. Further work involving a greater number of subjects and a three dimensional model would further answer the question as to whether these or other post-operative shoes have a significant effect on the knee adduction moment. PMID- 27408480 TI - Examination of a lumbar spine biomechanical model for assessing axial compression, shear, and bending moment using selected Olympic lifts. AB - BACKGROUND/AIMS: Loading during concurrent bending and compression associated with deadlift, hang clean and hang snatch lifts carries the potential for injury to the intervertebral discs, muscles and ligaments. This study examined the capacity of a newly developed spinal model to compute shear and compressive forces, and bending moments in lumbar spine for each lift. METHODS: Five male subjects participated in the study. The spine was modeled as a chain of rigid bodies (vertebrae) connected via the intervertebral discs. Each vertebral reference frame was centered in the center of mass of the vertebral body, and its principal directions were axial, anterior-posterior, and medial-lateral. RESULTS: The results demonstrated the capacity of this spinal model to assess forces and bending moments at and about the lumbar vertebrae by showing the variations among these variables with different lifting techniques. CONCLUSION: These results show the model's potential as a diagnostic tool. PMID- 27408482 TI - Geographic variation in fasciotomy during operative management of tibia fractures. AB - BACKGROUND: Diagnosis and treatment of acute or impending compartment syndrome (ACS) remains a clinical challenge. ACS is a clinical diagnosis, and may be associated with variation in its definition, as well as individual threshold for fasciotomy. We examined regional and state variation in rates of lower extremity fasciotomy associated with operatively managed tibia fractures. METHODS: A total of 313,344 surgically treated tibia fractures were identified via Current Procedural Terminology (CPT) codes using PearlDiver, a private-payer medical record database. Data from the PearlDiver database was compared to the National Trauma Data Bank trauma registry data to corroborate calculated fasciotomy rates. RESULTS: The aggregate United States fasciotomy rate derived from PearlDiver was 2.57%. State fasciotomy rates were wide-ranging (0.03%-11.86%) with an average state rate of 2.22% (n = 47, SD = 2.27). CONCLUSIONS: There was significant state to-state variation in the use of fasciotomy during operative management of tibial fractures. Various factors may have contributed to the observed difference of state fasciotomy rates. LEVEL OF EVIDENCE: This is a Level III epidemiological study retrospectively comparing geographic rates of fasciotomy during operative management of tibia fractures. PMID- 27408483 TI - Treatment of persistent forefoot adduction during ponseti method in treatment of idiopathic talipes equinovarus by minimal soft release. AB - INTRODUCTION: Abductor hallucies tenotomy sometimes necessary in treatment of clubfoot. MATERIAL AND METHODS: Thirty children (45 feet) of one day old up to six months presented with idiopathic clubfoot. Patients were treated using the technique of Ponseti combined by abductor hallucies tenotomy after serial casting. RESULTS: At a mean follow up period of 16.7 months, 43/45 feet were good (95%), 2/45 feet were bad (5%). The mean Pirani score at the final follow up was 1.05. CONCLUSION: Abductor hallucies tenotomy shortens the duration of casts, decrease the cost and risk of leg atrophy. PMID- 27408484 TI - Morbidity index: A score to assess immediate postoperative recovery in TKR patients. AB - BACKGROUND: Every surgical procedure involves certain amount of postoperative morbidity which varies among different surgeries and the same surgery done by different techniques. Minimally invasive surgeries have evolved in all surgical branches and are believed to have a lesser morbidity than the traditional procedures; however there is no score or index to assess the immediate recovery after any surgical procedure in the literature. We tried to devise an immediate postoperative assessment method that takes into account the early recovery phase of patient post total knee arthroplasty (TKA) from day1 to day3. We called it as morbidity index. It consists of a 10 different parameters which could overall assess the patient's postoperative recovery. MATERIALS & METHODS: A prospective study was conducted in order to evaluate feasibility of the morbidity index and its usefulness in assessing the immediate postoperative recovery in TKA. We evaluated 50 consecutive TKA patients and scored at day 1, day 2 and day 3 postoperatively by a morbidity index. RESULTS: The mean score on day one was 13.88 which decreased to 4.68 by day three indicating morbidity has decreased. CONCLUSIONS: The morbidity index can be a tool to assess the immediate postoperative recovery of the patient after TKA and can be used to compare different approaches and procedure. PMID- 27408485 TI - Assessment of failure of cemented polyethylene acetabular component due to bone remodeling: A finite element study. AB - The aim of the study is to determine failure of the cemented polyethylene acetabular component, which might occur due to excessive bone resorption, cement bone interface debonding and fatigue failure of the cement mantle. Three dimensional finite element models of intact and implanted pelvic bone were developed and bone remodeling algorithm was implemented for present analysis. Soderberg fatigue failure diagram was used for fatigue assessment of the cement mantle. Hoffman failure criterion was considered for prediction of cement-bone interface debonding. Results indicate fatigue failure of the cement mantle and implant-bone interface debonding might not occur due to bone remodeling. PMID- 27408486 TI - Shock attenuation properties at heel strike: Implications for the clinical management of the cavus foot. AB - BACKGROUND: This study explored the relationship between foot types and corresponding variations in shock attenuating properties of the heel. METHODS: Thirty matched participants were assigned to 3 groups: pronated, neutral, and supinated. A low-mass accelerometer was mounted to the calcaneus of the right leg of each participant. RESULTS: Acceleration at heel strike for supinators was significantly higher than that in individuals with pronated and neutrally aligned feet. No significant difference was found in mean and maximum acceleration at heel strike between pronators and neutrals. CONCLUSION: Cavus feet undergo significantly higher mean and maximum acceleration forces than neutrally aligned and pronated feet. PMID- 27408487 TI - Nonlinear analysis of postural sway in subjects with below knee amputation during opened and closed eye conditions. AB - OBJECTIVE: The aim of this study was to compare the structure of postural sway in healthy people and amputees with SACH foot (solid ankle cushion heel) and single axis foot during standing. METHODS: Twenty healthy, 10 amputees with single axis foot, and 10 amputees with SACH foot participated in this study. The structure of postural sway of the subjects was evaluated using approximate entropy (ApEn). RESULTS: People with SACH foot prosthesis exhibit increased regularity in postural sway compared to healthy people and people with single axis foot. CONCLUSION: Amputees who used single axis prosthesis achieved appropriate adaptation to their prosthesis device. PMID- 27408488 TI - Investigation of KryptoniteTM bone cement in hybrid screw configurations of locking plate humeral midshaft fixation: A study of surrogate bone model. AB - PURPOSE: Locking compression plates (LCP) allow trauma and orthopedic surgeons to have a variety of options for utilizing locking and non-locking screw features. In this study, the hybrid constructs of mixed unicortical and bicortical screws were investigated for humerus midshaft fractures. The locking and non-locking features were also incorporated into the hybrid LCP constructs. KryptoniteTM bone cement is biocompatible with low exothermic properties and strong metal adhesion. This novel bone cement was incorporated into the non-locking screw feature to compare its mechanical effect with that of a traditional locking screw feature. METHODS: A total of 24 synthetic bones (Sawbones((r)) Inc., USA) were equally divided into three groups (n = 8). The control group obtained traditional LCP fixation (JSM Medimax Inc., India) with bicortical screws, while the hybrid locking constructs employed a mix of bicortical and unicortical screws. The two bicortical screws in hybrid constructs were placed at the end holes of the LCP constructs and the unicortical screws were placed into the remaining holes. The hybrid locking (HL) group contained locking unicortical screws, whereas the hybrid non-locking group (HNK) utilized non-locking screw features incorporating the KryptoniteTM bone cement in the plate/screw bone construct. Specimens were tested by dynamic and static analysis. The eight total constructs were equally divided into two subgroups (n = 4) to conduct axial compression and torsion test individually. The low cyclic test was conducted for dynamic analysis, which included 10,000 cycles at 1 Hz frequency with a cyclic loading of 0-500 N of axial force for the axial compression test and 0-20 degrees of angular displacement for the torsion test. The static analysis was run by a failure test with a nondestructive strain rate of 0.1 mm/s for the axial compression test and 0.5 degrees s(-1) for the torsional test. The construct stiffness of axial compression and torsion were derived from the linear portion of the load displacement curves. The yield strength of axial compression and torsion was determined by using offset methods. The results of stiffness and yield strength were compared by using both one-way ANOVA and Scheffe and Games-Howell post hoc tests to analyze statically significant differences among the three groups. RESULTS: Specimens completed 10,000 cycles in the dynamic analysis of axial and torsional cyclic tests without major deformation. To compare with the control group in static analysis, the HL and HNK groups achieved positive effect in axial stiffness, 12.3% and 10.5% greater than the control group respectively. HL obtained axial yield strength about 12% less than the control group. The HNK group was equivalent with the control group in axial yield strength. The torsional stiffness and yield strength were found similar in three groups, which indicated torsional equivalence among them. The stiffness and yield strength from axial compression and torsion were found statically non-significant among three groups. CONCLUSIONS: Hybrid LCP constructs were initially showed to maintain equivalent axial and torsional stability with the traditional method. KryptoniteTM hosted mechanical and biological advantages for internal plate/screws (PLT) fixation. PMID- 27408489 TI - A practical way to prepare primer human chondrocyte culture. AB - Biological cartilage repair is one of the most important targets for orthopedic surgeons currently. For this purpose, it is mandatory to know how to prepare a chondrocyte culture. In this study, our purpose was to introduce a method enabling orthopedic surgeons to practice their knowledge and skills on molecular experimental setup at cellular level, based on our experiences from previous pilot studies. Thus, we believe it will encourage orthopedic surgeons. PMID- 27408490 TI - Difference in the acetabular cup orientation in standing and supine radiographs. AB - Acetabular orientation changes with that of the pelvis during lying and standing. This study was designed to measure these changes. We assessed 17 BHR replacements using EBRA software. The mean acetabular anteversion was more (p = 0.02) on erect than supine radiographs. Linear regression analysis showed that anteversion and inclination increased in some while decreased in others, and Bland and Altman analysis showed wide limits of agreement. The changes in acetabular orientation are thus subject to significant variations between the patients. We suggest studying the factors affecting acetabular orientation in standing to help reduce joint reaction forces and improve outcomes. PMID- 27408491 TI - Gait analysis and hip extensor function early post total hip replacement. AB - OBJECTIVE: The purpose of this study was to systematically evaluate the sagittal kinematic and kinetic gait patterns in patients in this early post-operative period, to describe them and to better understand the deficiencies in that gait pattern that may help to develop targeted rehabilitation strategies. METHODS: This study evaluated early gait patterns in 10 patients with isolated unilateral hip osteoarthritis who were post-operative for total hip replacement. Kinetic and kinematic assessments - focusing on sagittal plane abnormalities - were performed at 2 weeks pre-operatively and 8 weeks post-operatively. RESULTS: Our results demonstrated that while clinical scoring for pain and functional ability significantly improved post-operatively, as did clinical assessment of range of motion passively, this did not translate to the degree of dynamic improvement in gait. Step length and stride length did not improve significantly. Lack of hip extension in terminal stance associated with excessive anterior pelvic tilt persisted and was associated with a worsening in hip extensor power post operatively. CONCLUSION: Based on our results, post-operative rehabilitation programmes should include extensor muscle exercises to increase power and to retain the operative gain in passive range of motion, which would help to improve gait patterns. PMID- 27408492 TI - Biomechanical properties of tenotomy versus biceps knot in a cadaver model. AB - BACKGROUND: Biceps tenotomy and biceps tenodesis are the primary methods of treating biceps pathology. This study describes a new technique of tenotomy with the goal of autotenodesis to give the biceps a higher load to failure and decreased chance of a Popeye deformity. PURPOSE: The purpose of this study was to evaluate the strength of the "biceps knot", which is an outlet tenodesis of the biceps tendon and compare the biomechanical properties of this technique to tenotomy. METHODS: Ten matched cadaver shoulder pairs were used. In the tenotomy group, an arthroscopic tenotomy was performed at the labral biceps junction using a narrow angled biter. For the biceps knot group, a self-retrieving suture passing device was used to pass a suture as far lateral as possible. The suture was passed from just distal to the biceps insertion on the superior labrum and tied with a standard non-sliding arthroscopic knot. The humerus and biceps tendon were rigidly fixed to a materials testing machine and cyclically loaded at 10-20 N for 100 cycles at 1 Hz. After cyclic testing, a 2 N preload was placed on the tendon and the tendon was pulled in line with the bicipital groove until failure. RESULTS: The peak load to failure for the biceps knot was 58.9 N (SEM 8.2 N) and 37.3 N (SEM 4.6 N) for the tenotomy group (p = 0.046). The average stiffness for the biceps knot group was 4.2 N/mm (SEM 0.4 N/mm) and 3.2 N/mm (SEM 0.2 N/mm) for the tenotomy group (p = 0.031). CONCLUSION: Performing the biceps knot is a quick, easy and cost effective alternative to the current tenodesis options available. PMID- 27408493 TI - Orthopedic application of spikenard herbal rhizome decorated microstructured polymer biocomposites and their in vitro cytotoxicity. AB - The present study explores the synthesis of highly potential polymer biocomposite from Nardostachys jatamansi rhizome extract. The polymer biocomposites were synthesized from methyl methacrylate by free radical polymerization. ATR-IR enunciate the functional groups attributed at 956 cm(-1) (aromatic), a peak appeared at 1685 cm(-1) (-C 000000000000 000000000000 000000000000 111111111111 000000000000 111111111111 000000000000 000000000000 000000000000 O), 1186 cm(-1) (-O-CH3), 1149 cm(-1) (-C-O-C) framework and 1279 cm(-1) (-C-O), which are good agreement for the formation composites. The quantitative evaluations of antimicrobial studies were analyzed by serial dilution method and also improved activity in orthopedic infection pathogens. Cytocompatibility was analyzed by keratinocyte cell lines and it may be used for various biomedical applications. PMID- 27408494 TI - Biological fixation of total hip arthroplasty: Facts and factors. PMID- 27408495 TI - Visual loss after spine surgery: Case report. AB - The presence of postoperative visual loss is a well-known complication, and described in various reports, its low incidence (0.028-0.2%) makes it extremely rare. Two main causes have been determined: Posterior Ischemic Optic Neuropathy and central Retinal Artery Oclusion. The following is a case report of a 52-year old patient that presented visual loss after elective spine surgery that had no complications that could initially explain this complication. Studies were performed and evaluations by ophthalmologists determined that the cause of Posterior Ischemic Optic Neuropathy due to multiple risk factors that the patient had previously and during the surgery. After 3 year follow-up the patient still has total visual loss and no other complications were reported. PMID- 27408496 TI - Plate augmentation with retention of intramedullary nail is effective for resistant femoral shaft non-union. AB - OBJECTIVE: Non-union after intramedullary nail fixation of femur shaft fractures is although infrequent but a challenging condition to treat. The treatment options available to deal with such a situation include exchange nailing, removal of nail and re-osteosynthesis with plating, or Ilizarov fixation. We believe that rotational instability, in the presence of a nail, is one of the main reasons for most of the non-union. We present our experience of plate augmentation leaving the nail in situ for non-union of femoral shaft fracture. METHODS: In this retrospective study, we had operated 16 cases of the femoral shaft non-union, which were treated by plate augmentation and bone grafting (if needed) with retention of the intramedullary interlocking nail in situ. The cases of infected non-union and any fracture less than one-year duration were excluded from the study. RESULTS: Bone grafting was done only in 4 cases with atrophic non-union. We could achieve union in all the cases at an average time of 6.25 months. The average time of surgery between the primary surgery of interlocking nail fixation and the plate augmentation was 13 months. Mean surgical time for plate augmentation and bone grafting was 71 min. No major complication or implant failure was encountered. An average residual shortening of the limb was 0.9 cm and average range of motion of the knee was 115 degrees . CONCLUSION: Plate augmentation seems an effective, reliable, safe and an easy procedure for the treatment of femoral shaft non-union after an intramedullary nailing. PMID- 27408497 TI - Single-step scaffold-based cartilage repair in the knee: A systematic review. AB - Chondral lesions are difficult-to-treat entities that often affect young and active people. Moreover, cartilage has limited intrinsic healing potential. The purpose of this systematic literature review was to analyse whether the single step scaffold-based cartilage repair in combination with microfracturing (MFx) is more effective and safe in comparison to MFx alone. From the three identified studies, it seems that the single-step scaffold-assisted cartilage repair in combination with MFx leads to similar short- to medium-term (up to five years follow-up) results, compared to MFx alone. All of the studies have shown improvements regarding joint functionality, pain and partly quality of life. PMID- 27408498 TI - Spinal infections in children: A review. AB - Spinal infections are uncommon but significant causes of morbidity and hospitalization in the paediatric population. These infections encompass a broad range of conditions, from discitis to osteomyelitis and spinal epidural and intramedullary abscesses. Paediatric spinal infections can be caused by a range of bacterial, viral, fungal and parasitic agents. Ultrastructural differences of the vertebrae and associated structures result in distinct mechanisms of pathogenesis of spinal infections in children compared to adults. The non specific nature of symptoms produced by them can cause considerable diagnostic delays. Magnetic Resonance (MR) imaging can facilitate early identification of the disease, and distinguish it from other spinal pathologies. The association of antimicrobial resistant bacterial strains from some of the cases appears worrisome; as is the increasing incidence of Kingella kingae infections causing spinal infections. Rest and immobilization are the general treatment, and prompt initiation of antimicrobial therapy is warranted to ensure optimal clinical outcome. Most patients generally have a good prognosis; however, early identification and prompt initiation of antimicrobial therapy is essential to achieve the best therapeutic response. PMID- 27408499 TI - Total hip arthroplasty in the developmental dysplasia of the hip using transverse subtrochanteric osteotomy. AB - BACKGROUND: We assessed the results of the transverse subtrochanteric femoral shortening osteotomy technique and the cementless THA process applied to Crowe type III and IV patients with developmental dysplasia of the hips. METHODS: We retrospectively evaluated 25 patients (32 hips) between 2006 and 2014. RESULTS: The mean follow-up time was 5.1 years. The mean preoperative Harris hip score was 49.5, which increased to 87.1 postoperatively. The mean preoperative leg-length discrepancy was 3.6 cm; the mean postoperative discrepancy was 0.5 cm. CONCLUSION: THA with subtrochanteric femoral shortening osteotomy technique is an effective technique for treating developmental dysplasia of the hip. PMID- 27408500 TI - Geographic variations in orthopedic trauma billing and reimbursements for hip and pelvis fractures in the Medicare population. AB - We investigated geographic variations in Medicare spending for DRG 536 (hip and pelvis fracture). We identified 22,728 patients. The median number of charges, discharges, and payments were recorded. Hospitals were aggregated into core based statistical (CBS) areas and the coefficient of variation (CV) was calculated for each area. On average, hospitals charged 3.75 times more than they were reimbursed. Medicare charges and reimbursements demonstrated variability within each area. Geographic variation in Medicare spending for hip fractures is currently unexplained. It is imperative for orthopedists to understand drivers behind such high variability in hospital charges for management of hip and pelvis fractures. PMID- 27408501 TI - Traumatic hip dislocation in Cotonou. AB - PURPOSE: Traumatic hip dislocation is an emergency. We studied their epidemiological, and therapeutic characteristics at Cotonou. METHODS: This was a retrospective study from 2006 to 2014 including all inpatient for traumatic hip dislocation, whose minimum follow-up was 12 months. RESULTS: Twenty-three cases in which 19 males were selected. The mean age was 39.6 years. It was mainly fracture-dislocations (17 cases). Sixteen dislocations were posterior. Reduction average delay was 41.0 h. The treatment was mainly orthopedic (16 cases). Few complications were noted: two osteoarthritis, one death. The functional results were excellent (8 cases), very good (4 cases) and good (8 cases). CONCLUSION: Traumatic hip dislocations require early reduction to avoid complications. PMID- 27408502 TI - The clinical implications of heterotopic ossification in patients treated with radial head replacement for trauma: A case series and review of the literature. AB - Radial head arthroplasty (RHA) is an acceptable treatment for comminuted radial head fractures (RHF). Fourteen patients with no postop HO prophylaxis were treated with RHA for comminuted RHF. A 50% incidence in HO was seen following RHA with a statistically increased risk (p <= 0.05) of reoperation compared to those without HO. Decreased ROM was seen on the affected side (p <= 0.05); patients without HO showed no statistical difference (p >= 0.05) in ROM or grip strength. HO following RHA increases patient risk for reoperation and decreases ROM. We recommend HO prophylaxis with NSAIDs and/or radiotherapy if no direct patient contraindications are found. PMID- 27408503 TI - Management of burst fractures in the thoracolumbar spine. AB - The most common fractures in the spine take place in the thoracolumbar region. Currently there is no consensus regarding optimum treatment. OBJECTIVE: Analyze the current medical literature available regarding treatment of compression fractures of the thoracolumbar spine. METHODS: Research of current literature in medical databases. RESULTS: Regarding current available literature, we found no consensus in the treatment of compression fractures in the thoracolumbar spine. CONCLUSIONS: Burst fractures of the thoracolumbar junction is a very common condition, treatment of each patient must be individualized. Conservative treatment is recommended for stable fractures without neurological compromise and less than 35 degrees of kyphosis. PMID- 27408504 TI - Noise production in ceramic-on-ceramic total hip arthroplasty is associated with lower patient satisfaction and hip scores. AB - BACKGROUND: Ceramic-on-ceramic total hip arthroplasties (THA) are commonly implanted. We investigated the incidence of noise in ceramic-on-ceramic and determined any association with patient satisfaction and hip scores. METHODS: We recruited 140 THA. Questionnaires were completed to assess the incidence and frequency of noise, and satisfaction level. Hip and SF-12 scores were recorded. RESULTS: Forty-two patients (30%) were aware of noise production. Patients with noise production had lower satisfaction, mean hip and SF-12 scores than those with silent hips. CONCLUSION: Given the high incidence of noise in ceramic-on ceramic THA, patients should be counselled on this risk pre-operatively. PMID- 27408505 TI - Evaluation of lower limb axial alignment using digital radiography stitched films in pre-operative planning for total knee replacement. AB - BACKGROUND: For patients with knee osteoarthritis, even slight anatomical variations in the femur or the tibia could affect total limb alignment during total knee replacement (TKR). Our hypothesis implies that the femoral valgus correction angle (VCA) in patients indicated for TKR, is variable and higher than the reported norm of 6 degrees utilized in most intramedullary instrumentation systems, and that tibial bowing may result to a disparity of the tibial mechanical axis to the anatomical axis. METHODS: Our study is a retrospective review of 216 pre-operative arthritic knees, which investigated the lower limb axial alignment using digitally-stitched films. Patients excluded from the study are those with history of previous tibial or femoral osteotomy, secondary gonarthrosis, rheumatoid arthritis, previous femoral or tibial fracture, patients for bilateral TKR, or history of hip surgery. RESULTS: The mean age was 68-years old (range 39-86 years). The mean VCA was 7 degrees (4.7-9.3) for men and 6.6 degrees (4.9-9) for women. However, 71 patients (33%) had more than 7 degrees VCA. Subsequently, 46 patients (21%) had tibial bowing producing an angle >1.5 degrees between its mechanical and anatomic axis. CONCLUSIONS: The 6 degrees standard when used as a guide may result in suboptimal prosthesis positioning during conventional TKR surgery. Therefore our findings suggest that the femoral valgus correction angle has a broad range, and using standard femoral intramedullary guides should not be overlooked. PMID- 27408506 TI - Preoperative assessment of femoral rotation and its relationship with coronal alignment: A magnetic resonance imaging study. AB - This MRI study explores the individual variation of the rotational axes of the distal femur, and investigate the relationship of this variation with overall coronal alignment in the osteoarthritic knee,The mean surgical epicondylar axis (SEA) was 1.7 degrees , anatomical epicondylar axis (AEA) 5.6 degrees and AP trochlea axis (APA) 94.3 degrees external rotation, compared to the posterior condylar line. Investigating this relationship between different coronal alignment groups, there were statistically significant differences between excessive varus and excessive valgus knees for SEA (0.9:3.0 p < 0.001) and AEA (4.7:7.0 p < 0.001). There was no statistical difference for APA (93.9:95.3 p = 0.238). PMID- 27408507 TI - A valuable technique for femoral stem revision in total hip replacement: The in cement revision - A case series and technical note. AB - Revision of a cemented femoral stem can be a challenging procedure. We present a series of cases utilising the "In-cement" revision, whereby the same size stem is introduced into the original cement mantle, without additional cementing. It requires a stable cement mantle in the correct version. We describe the technique and present a review of 23 revision total hip replacements performed over a 5 year period. At average follow-up of 67 months (12-128 months), the overall survivorship was 91.3% with no patient requiring re-revision for stem loosening or mechanical failure. Two patients required re-revision for infection and one of those patients is now deceased. No further operations were required in 21 patients. The "In-cement" revision can be a valuable technique for the revision arthroplasty surgeon. Early results suggest this is a safe and effective technique in the appropriate patient. PMID- 27408508 TI - Midterm results following uncemented, modular, fully porous coated stem used in revision total hip arthroplasty: Comparison of two stem systems. AB - BACKGROUND: Aim of this study was to evaluate stem subsidence and survivorship of implant following implantation of Revitan (Zimmer) and MP (Waldemar Link) stems. METHODS: Retrospective case series with clinical and radiological follow-up of 1 10 years. RESULTS: 47 Revitan and 57 MP stems were analyzed. In 12 cases there was subsidence of the stem present. Two Revitan stems and one MP stem were revised as a result of subsidence. Failure rate was 4.3% for Revitan, 1.8% for MP stem and difference was not statistically significant. CONCLUSION: There is no significant difference in subsidence or survivorship between Revitan and MP stems. PMID- 27408509 TI - Ten-year follow-up results of posterior instrumentation without fusion for traumatic thoracic and lumbar spine fractures. AB - BACKGROUND: This retrospective study aims to present and evaluate the long follow up results of posterior instrumentation without fusion in patients with traumatic thoracic and lumbar fractures. METHODS: 45 patients were operated. The mean follow-up period was 147.6 months. Sagittal plane kyphosis (SPK) and anterior wedge angle (AWA) were evaluated in preoperative and follow-up. RESULTS: SPK and AWA improved significantly in the early postoperative. However, the correction was lost in the 10-year follow-up. The loss of correction was statistically significant in SPK and AWA. CONCLUSION: Posterior instrumentation without fusion is still among the most useful in treatment of traumatic thoracolumbar fractures. PMID- 27408510 TI - Low intensity pulsed ultrasound in the treatment of long bone nonunions: Evaluation of cytokine expression as a tool for objectifying nonunion therapy. AB - BACKGROUND: Nonunion is one of the most common complications in bone healing. After several clinical studies, the effect of low intensity pulsed ultrasound (LIPUS) in the treatment of nonunions remains unclear because of the difficulty in evaluating its effect on bone healing. In former studies, the analysis of serum cytokine expression patterns over time has proven to be an objective method for showing the bone healing process and evaluating nonunion therapies. This study evaluates LIPUS as a treatment option for patients with nonunions based on the analysis of serum cytokine expression. METHODS: In this prospective, single institution study, venous blood samples from 23 patients were taken from October 2012 to October 2013 before starting LIPUS therapy and at the end of week 1 and 2 and after 1, 2, and 3 months. Patients attended clinical and radiological follow up examinations at the same intervals. After treating all patients according to the LIPUS therapy protocol, we divided them into two groups: Group 1 consisted of patients with healing at the nonunion site, and Group 2 consisted of patients with failed nonunion therapy. We measured transforming growth factor-beta1 (TGF beta1), platelet-derived growth factor (PDGF), and basic fibroblastic growth factor (bFGF) at all time-points. RESULTS: The TGF-beta1 serum concentration increased from the pre-treatment value to 1 week within the unsuccessful group. Otherwise, no significant differences between groups in measured cytokines during LIPUS therapy could be detected. CONCLUSION: Our findings suggest that LIPUS does not lead to a significant increase in cytokine levels in patients with nonunions. It is likely that "successful" treatment can be attributed to spontaneous healing. Our results suggest that LIPUS is not a proper treatment for long bone nonunions. PMID- 27408511 TI - An extremely rare case of a glomus tumor in the popliteal fossa. AB - Glomus tumors are the benign perivascular tumors that typically present with hypersensitivity to cold, paroxysmal severe pain, and pinpoint tenderness. This tumor is usually subungual lesions and accounts for 1.6% of all soft-tissue tumors. However, extradigital glomus tumors are extremely rare and can be difficult to diagnose, as they typically have a diameter of less than about 1 cm. We report a glomus tumor in the popliteal fossa of a 17-year-old male patient who experienced severe posterior knee pain while playing sports. A physical examination did not reveal a mass, although a glomus tumor was identified in the popliteal fossa using magnetic resonance imaging. We successfully performed open excision to remove the tumor, and the patient achieved a restored postoperative gait and could perform sports activities with no pain. These tumors are extremely rare in the knee area, and typically have a diameter of less than about 1 cm, which can complicate their diagnosis and treatment, despite the presence of severe pain. Therefore, we recommend that clinicians be aware of extradigital glomus tumors, as careful imaging can facilitate an early diagnosis and treatment. PMID- 27408513 TI - Fentanyl Patch Fatalities: We ALL Have a Role in Prevention! AB - We all have a role in preventing fentanyl patch tragedies. PMID- 27408514 TI - HHS Walks the Middle Ground in Final Ruling on Nondiscrimination: Drug Access and Formulary Construction Still Unguided. AB - HHS walks a middle ground in final nondiscrimination rule. PMID- 27408512 TI - Is there a treatment protocol in which platelet-rich plasma is effective? AB - AIM: We aimed to reveal whether there are prospective suggestions for effective and standard platelet-rich plasma applications. METHODS: We searched for clinical trials and traced all the references of incorporated documents. RESULTS: In literature, there was no study indicating which disease is treated by which mechanism of action, how much dose and content are prepared and applied, when the treatment is applied and how many cures are applied. CONCLUSION: Guides introducing which concentrations of PRP are used for which diseases are to be prepared immediately by a committee which is comprised of primarily orthopedists, clinical pharmacologists and toxicologists. PMID- 27408515 TI - Drug and Device News. AB - Approvals, new indications, regulatory activities, and more. PMID- 27408516 TI - Pharmaceutical Approval Update. AB - Defibrotide sodium (Defitelio) for hepatic veno-occlusive disease; emtricitabine/tenofovir alafenamide (Descovy) for human immunodeficiency virus infection; and infliximabdyyb (Inflectra) for Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. PMID- 27408517 TI - Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. AB - Brexpiprazole (Rexulti): a new monotherapy for schizophrenia and adjunctive therapy for major depressive disorder. PMID- 27408518 TI - CMS to Test Enhanced Medication Therapy Management Model: Aims for Greater Use of Pharmacists, Cost Savings, and Better Outcomes. AB - A new test model starting in five regions in 2017 seeks better integration of pharmacists into the Medicare Part D Medication Therapy Management program, which has severely underperformed since the Part D benefit took effect in 2006. PMID- 27408519 TI - Immunization in the United States: Recommendations, Barriers, and Measures to Improve Compliance: Part 1: Childhood Vaccinations. AB - Childhood vaccination is one of the most effective public health strategies to control and prevent disease, but some parents decline or delay vaccinating their children. A variety of measures have been suggested to overcome vaccine noncompliance. PMID- 27408520 TI - Investigation of the Selection and Timing of Pharmacological Therapy in Community Acquired Bacterial Meningitis. AB - BACKGROUND: Bacterial meningitis is responsible for significant morbidity and mortality, but early appropriate therapy is expected to improve outcomes. National treatment guidelines were published in 2004, but no assessment of their utilization in the U.S. has been reported. OBJECTIVES: To measure adherence to meningitis treatment guidelines and describe patient outcomes in relation to recommended antibiotic and dexamethasone use. METHODS: Retrospective chart reviews were performed on patients with bacterial meningitis who presented to emergency departments at two community teaching hospitals. Timing and appropriateness of antibiotic and dexamethasone use were assessed according to national guidelines. Patient outcomes of mortality, length of hospitalization, and neurological complications were analyzed based on therapies received. RESULTS: A total of 161 cases were identified; 38 met inclusion criteria. Recommended antibiotic regimens were administered to 52.6% of patients, while 26.3% received that regimen within eight hours. Dexamethasone was used in 44.7% of patients, but was administered prior to antibiotics in only 10.5% of cases. Mortality was numerically lower with recommended antibiotic therapy but did not reach statistical significance (5.0% versus 16.7%; P = 0.33). Median length of stay was eight days for patients who received recommended antibiotics and 11 days for those who did not (P = 0.69). One patient who received dexamethasone had a neurological complication at discharge compared with four patients not receiving dexamethasone (5.9% versus 19.0%, P = 0.35). CONCLUSION: Current treatment guidelines provide clinicians with direction on optimal care for patients with bacterial meningitis, and an opportunity exists to improve implementation of these recommendations, which could improve patient outcomes. PMID- 27408521 TI - Prevalence of Delirium and Coma In Mechanically Ventilated Patients Sedated With Dexmedetomidine or Propofol. AB - OBJECTIVE: To assess the prevalence of delirium and coma in mechanically ventilated patients sedated with dexmedetomidine or propofol alone; to evaluate the hospital length of stay for both treatment groups; and to evaluate the level of sedation, adverse effects, and hospital outcomes. METHODS: Medical records were reviewed retrospectively for patients who were admitted to the medical or surgical intensive care units (ICUs) in a 591-bed teaching hospital and who received either dexmedetomidine or propofol alone for 24 hours or more for sedation. RESULTS: A total of 111 patients were included in the study, with 56 patients in the dexmedetomidine group and 55 patients in the propofol group. Results of the analysis showed that the propofol group had a higher prevalence of coma (43.6% versus 12.5%; P < 0.001). Dexmedetomidine patients had a longer median hospital length of stay of 23.5 days (interquartile range [IQR], 11.5-39.5 days) versus 15.0 days (IQR, 7.0-24.0 days; P = 0.01). The rates of delirium were similar in both groups, with 16% in dexmedetomidine-treated patients versus 20% in propofol-treated patients (P = 0.63). CONCLUSION: No difference in the prevalence of delirium was found when comparing the dexmedetomidine- and propofol treated groups. Propofol was associated with more coma and oversedation; dexmedetomidine was associated with longer time to extubation, longer length of stay in the ICU, and longer hospital length of stay. PMID- 27408522 TI - Digestive Disease Week And American Society of Clinical Oncology. AB - We report on key Digestive Disease Week sessions that focused on hepatitis C virus and Clostridium difficile infection, colonoscopy preparation, irritable bowel syndrome, and Crohn's disease. We also review major American Society of Clinical Oncology sessions on breast, pancreatic, ovarian, skin, and brain cancers and multiple myeloma. PMID- 27408523 TI - Research Briefs. PMID- 27408524 TI - The genus Bebryce (Cnidaria, Octocorallia, Plexauridae) at Japan, with descriptions of three new species. AB - Three new deep-water species of Bebryce from Japan are described and depicted using Scanning Electron Microscopy: Bebryce otsuchiensis sp. n., Bebryce rotunda sp. n., and Bebryce satsumaensis sp. n. Bebryce studeri Whitelegge, 1897, was reported from Japanese waters for the first time, bringing the total of Japanese Bebryce species to six. Five of these six species seem to be endemic to Japanese waters and all occur in deep water up to 213 m. A key to the Bebryce species is presented. PMID- 27408525 TI - A new termite (Isoptera, Termitidae, Syntermitinae, Macuxitermes) from Colombia. AB - A new species of termite, Macuxitermes colombicus Postle & Scheffrahn is described from soldiers and workers collected from Departamento Magdalena, Colombia. The soldier of Macuxitermes colombicus differs from its lone congener in having no protuberances on the head capsule. PMID- 27408526 TI - An annotated checklist of Microweiseinae and Sticholotidini of Iran (Coleoptera, Coccinellidae). AB - An updated checklist of the Coccinellidae species of the former subfamily Sticholotidinae recorded from Iran is provided. Eleven species are reported: two species classified presently in the subfamily Microweiseinae (in the genera Paracoelopterus Normand, 1936 and Serangium Blackburn, 1889), and nine species classified in the tribe Sticholotidini of the subfamily Coccinellinae (in the genera Coelopterus Mulsant & Rey, 1852 and Pharoscymnus Bedel, 1906). Pharoscymnus smirnovi Dobzhansky, 1927 is removed from the list of the Coccinellidae of Iran. Distribution of species in Iranian provinces is presented. Data concerning their host plants along with their prey species are also included when known. Morphological features of two rarely collected and poorly known species of Iranian fauna, Pharoscymnus brunneosignatus Mader, 1949 and Pharoscymnus pharoides (Marseul, 1868) are diagnosed and illustrated. PMID- 27408527 TI - Review of Dolichostyrax Aurivillius (Cerambycidae, Lamiinae) in Borneo, with descriptions of three new genera and the first case of (ovo)viviparity in the long-horned beetles. AB - We reviewed the species of genus Dolichostyrax Aurivillius (Cerambycidae: Morimopsini) from Borneo, which included the redescriptions of two species - Dolichostyrax moultoni Aurivillius, 1911 and Dolichostyrax longipes Aurivillius, 1913, with the first female description for the latter. After the examination of the additional material previously identified as Dolichostyrax, we described three new genera - Borneostyrax gen. n., Microdolichostyrax gen. n., and Eurystyrax gen. n. Borneostyrax cristatus sp. n. was described based on the male and female specimens, whilst Microdolichostyrax hefferni sp. n., Microdolichostyrax minutus sp. n. and Eurystyrax nemethi sp. n. are known only from females. All studied species are distributed in the mountain regions of Sabah, with the exception of Dolichostyrax moultoni from Sarawak. An identification key to the genera of Bornean Morimopsini and species of Dolichostyrax, Borneostyrax gen. n., Microdolichostyrax gen. n. and Eurystyrax gen. n. is provided and their distributions and intraspecific morphological variability are discussed. The short and wide ovipositor, loss of spermatheca, and presence of large larvae without apparent eggbursters inside the female abdomens indicate the presence of (ovo)viviparity in Borneostyrax gen. n. This is the first case of this rare phenomenon within Cerambycidae. PMID- 27408528 TI - A revision of the Chinese Aulacidae (Hymenoptera, Evanioidea). AB - The Chinese Aulacidae are revised, keyed and illustrated for the first time. In total twenty-five species are recorded from China, included within two genera Aulacus Jurine, 1807 and Pristaulacus Kieffer, 1900, with five and twenty species respectively. Among the treated species, six are newly described for science: Aulacus magnus sp. n., Pristaulacus calidus sp. n., Pristaulacus centralis sp. n., Pristaulacus fopingi sp. n., Pristaulacus obscurus sp. n., and Pristaulacus pseudoiosephi sp. n. Three species are newly recorded from China: Pristaulacus excisus Turner, 1922, Pristaulacus iosephi Turrisi & Madl, 2013, and Pristaulacus rufobalteatus Cameron, 1907. PMID- 27408529 TI - Braconinae parasitoids (Hymenoptera, Braconidae) emerged from larvae of Lobesia botrana (Denis & Schiffermuller) (Lepidoptera, Tortricidae) feeding on Daphne gnidium L. AB - Bracon admotus Papp, 2000, and three species of the genus Habrobracon Ashmead, 1895, Habrobracon concolorans (Marshall, 1900), Habrobracon hebetor (Say, 1836) and Habrobracon pillerianae Fischer, 1980, were obtained from the larvae of Lobesia botrana (Denis & Schiffermuller, 1775) (Lepidoptera, Tortricidae) feeding on Daphne gnidium Linnaeus, 1753 (Thymelaeaceae) in the natural reserve of Migliarino-San Rossore-Massaciuccoli (Pisa-Central Italy). Bracon admotus, Habrobracon concolorans and Habrobracon pillerianae were found for the first time to be associated with Lobesia botrana, while Habrobracon hebetor was reared for the first time from the larvae of Cryptoblabes gnidiella (Milliere, 1867) (Lepidoptera, Pyralidae, Phycitinae) that was found on the same host plant. Bracon admotus and Habrobracon pillerianae are new to the fauna of Italy and Western Europe. A key is proposed for the determination of Habrobracon species reared from Lobesia botrana and related Palaearctic species of this genus. Habrobracon lineatellae Fisher, 1968 is considered as a valid species. PMID- 27408530 TI - Two new species of the genus Panorpa Linnaeus (Mecoptera, Panorpidae) from Yunnan, China. AB - Two new scorpionfly species, Panorpa reflexa sp. n. and Panorpa parallela sp. n., are described and illustrated from Yunnan Province, China. Panorpa reflexa can be readily differentiated from its congeners by the 3-shaped parameres in male genitalia. Panorpa parallela is unique for its parallel parameres in male genitalia. The number of Panorpa species is raised to four in Yunnan Province, and to 113 throughout China. PMID- 27408531 TI - Synopsis of Central Andean Orthalicoid land snails (Gastropoda, Stylommatophora), excluding Bulimulidae. AB - A faunal overview is presented of the molluscan families Amphibulimidae, Megaspiridae, Odontostomidae, Orthalicidae, Simpulopsidae in Bolivia, Ecuador, and Peru. These Central Andean countries are known for their biodiverse malacofauna, of which the superfamily Orthalicoidea takes relatively a large share. In this paper the five families containing 103 (sub)species, for which systematic information (original publication, type locality, type depository, summarizing literature) and distributional records are presented. All species are illustrated by photographs of the type material or, if this could not be located, by a reproduction of the original figure. The following new taxon is introduced: Thaumastus (Thaumastus) sumaqwayqu sp. n. Junior subjective synonyms are established for: Plekocheilus (Sparnotion) Pilsbry, 1944 = Plekocheilus (Eudolichotis) Pilsbry, 1896; Scholvienia (Thomsenia) Strebel, 1910 = Scholvienia Strebel, 1910; Sultana (Trachyorthalicus) Strebel, 1909 = Sultana (Metorthalicus) Pilsbry, 1899; Plekocheilus (Eurytus) conspicuus Pilsbry, 1932 = Thaumastus (Thaumastus) hartwegi (Pfeiffer in Philippi, 1846); Zebra gruneri Strebel, 1909 = Orthalicus maracaibensis (Pfeiffer, 1856); Scholvienia jaspidea minor Strebel, 1910 = Scholvienia alutacea (Reeve, 1850); Bulimus bifasciatus unicolor Philippi, 1869 = Scholvienia brephoides (d'Orbigny, 1835). A new status is given to Plekocheilus mcgintyi 'Pilsbry' H.B. Baker, 1963 (subspecies of Bulinus piperitus Sowerby I, 1837); Strophocheilus superstriatus var. prodeflexus Pilsbry, 1895 (subspecies of Bulinus piperitus Sowerby I, 1837); Thaumastus (Quechua) salteri maximus Weyrauch, 1967 (subspecies of Thaumastus (Quechua) olmosensis Zilch, 1954); Pseudoglandina agitata Weyrauch, 1967 (nomen inquirendum). New combinations are: Clathrorthalicus corydon (Crosse, 1869), and Cyclodontina chuquisacana (Marshall, 1930). Lectotypes are now designated for Bulimus incisus Hupe, 1857 and Bulinus piperitus Sowerby I, 1837. PMID- 27408532 TI - Species of Elasmogorgia and Euplexaura (Cnidaria, Octocorallia) from Japan with a discussion about the genus Filigella. AB - Octocorals with thread-like colony shape have been re-examined, mainly from Japanese waters. The holotypes of Elasmogorgia filiformis and Filigella boninensis and a syntype of Filigella mitsukurii have been studied. Euplexaura arbuscula is identified and Euplexaura yayoii sp. n. described. PMID- 27408533 TI - The first revision of the carnivorous land snail family Streptaxidae in Laos, with description of three new species (Pulmonata, Stylommatophora, Streptaxidae). AB - The family Streptaxidae in Laos is revised. Twelve species are known, mainly from limestone areas, in the genera Discartemon Pfeiffer, 1856, Perrottetia Kobelt, 1905, Haploptychius Mollendorff, 1906, and Indoartemon Forcart, 1946. Three new species, Perrottetia unidentata sp. n. and Perrottetia megadentata sp. n. from northern and central Laos, and Indoartemon diodonta sp. n. from central Laos, are described. All eight species of these three genera previously recorded from Laos are revised and discussed based on examined material from Laos, Cambodia, Vietnam and Thailand. Type material was examined and lectotypes are designated. Details of genital anatomy and radulae are provided, including the first detailed genitalia and radula descriptions from Haploptychius. Two novelties in Streptaxidae, a vaginal caecum, and the occurrence of aphallic individuals, are reported from Haploptychius pellucens (Pfeiffer, 1863). PMID- 27408534 TI - The mitochondrial genome of the land snail Cernuella virgata (Da Costa, 1778): the first complete sequence in the family Hygromiidae (Pulmonata, Stylommatophora). AB - The land snail Cernuella virgata (da Costa, 1778) is widely considered as a pest to be quarantined in most countries. In this study, the complete mitochondrial genome of Cernuella virgata is published. The mitochondrial genome has a length of 14,147 bp a DNA base composition of 29.07% A, 36.88% T, 15.59% C and 18.46% G, encoding 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes and two ribosomal RNA (rRNA) genes. The complete nucleotide composition was biased toward adenine and thymine, A+T accounting for 69.80%. Nine PCGs and 14 tRNA genes are encoded on the J strand, and the other four PCGs and eight tRNA genes are encoded on the N strand. The genome also includes 16 intergenic spacers. All PCGs start strictly with ATN, and have conventional stop codons (TAA and TAG). All tRNAs fold into the classic cloverleaf structure, except tRNA(Arg) , tRNA(Ser(UCN)) , tRNA(Ser(AGN)) and tRNA(Pro) . The first three lack the dihydrouridine arm while the last lacks the TpsiC arm. There are 502 bp long noncoding regions and 418bp long gene overlaps in the whole mitochondrial genome, accounting for 3.54% and 2.95% of the total length respectively. Phylogenetic analyses based on the sequences of the protein coding genes revealed a sister group relationship between the Hygromiidae and the Helicidae. PMID- 27408535 TI - Three new species of Misionella from northern Brazil (Araneae, Haplogynae, Filistatidae). AB - Three new species of the genus Misionella are described from Brazil: Misionella carajas sp. n. and Misionella aikewara sp. n. from caves in the states of Para and Tocantins and Misionella pallida sp. n. from natural and synanthropic dry areas in the states of Piaui, Maranhao, Rio Grande do Norte and Bahia. These species seem to belong to a distinct group within the genus; the males have an elongate palpal tibia and bulb, a pair of characteristic and hirsute macrosetae in the second metatarsus and the females have internal genitalia with only one pair of spermathecae, with relatively short ducts, lacking the auxiliary receptacles. Their phylogenetic placement and geographic distribution are briefly discussed. PMID- 27408536 TI - Taxonomic recovery of the ant cricket Myrmecophilus albicinctus from M. americanus (Orthoptera, Myrmecophilidae). AB - Myrmecophilus americanus and Myrmecophilus albicinctus are typical myrmecophilous insects living inside ant nests. These species are ecologically important due to the obligate association with tramp ant species, including harmful invasive ant species. However, the taxonomy of these "white-banded ant crickets" is quite confused owing to a scarcity of useful external morphological characteristics. Recently, Myrmecophilus albicinctus was synonymized with Myrmecophilus americanus regardless of the apparent host use difference. To clarify taxonomical relationship between Myrmecophilus albicinctus and Myrmecophilus albicinctus, we reexamined morphological characteristics of both species mainly in the viewpoint of anatomy. Observation of genitalia parts, together with a few external body parts, revealed that Myrmecophilus albicinctus showed different tendency from them of Myrmecophilus americanus. Therefore, we recover Myrmecophilus albicinctus as a distinct species on the basis of the morphology. PMID- 27408537 TI - Three new species of Osmylus Latreille from China (Neuroptera, Osmylidae). AB - Three new species of Osmylus Latreille are described from China: Osmylus maoershanicola sp. n., Osmylus shaanxiensis sp. n. and Osmylus angustimarginatus sp. n. These new species are distinguishable from other related species by the shape of the 9(th) tergite of both sexes, as well as the shape of gonarcus, mediuncus and spermatheca. A key is given to differentiate Palaearctic and Oriental species of Osmylus. PMID- 27408538 TI - The morphology of the immature stages of Metadonus vuillefroyanus (Capiomont, 1868) (Coleoptera, Curculionidae, Hyperini) and notes on its biology. AB - Last instar larva and pupa of Metadonus vuillefroyanus (Capiomont, 1868) (Curculionidae: Hyperini) are described and compared with known larvae of the other 43 hyperine taxa. The thorn-like setae located on distinct black protuberances on the larval body are characteristic features of the genus Metadonus and the subgenus Eririnomorphus of the genus Hypera. The biological singularity of this species was studied and described. The variable colouration of larvae has been confirmed in association with the variability of the host plant's colouration at the studied localities. This species' reported inability to spin cocoons has been disproven. A different type of cocoon with two layers, where the inner layer consists of proteins from Malpighian tubules while the outer layer contains soil particles, is described. This type of cocoon is unique compared with those known from other hyperines, which usually pupate on or above the ground and do not use substrate particles in building their cocoons. PMID- 27408539 TI - Sergey gen. n., a new doryctine genus from temperate forests of Mexico and Cuba (Hymenoptera, Braconidae). AB - The new doryctine genus Sergey gen. n. is described with four new species (Sergey cubaensis Zaldivar-Riveron & Martinez, sp. n., Sergey coahuilensis Zaldivar Riveron & Martinez, sp. n., Sergey tzeltal Martinez & Zalidivar-Riveron, sp. n., Sergey tzotzil Martinez & Zalidivar-Riveron, sp. n.) from temperate forests of Mexico and Cuba. Similar to many other doryctine taxa, the new genus has a considerably elongated, petiolate basal sternal plate of the first metasomal tergite, although it can be distinguished from these by having the mesoscutum sharply declivous anteriorly with sharp anterolateral edges. The described species have been characterised molecularly based on two mitochondrial (COI, cyt b) and one nuclear (28S) gene markers. Based on the mitochondrial gene genealogies reconstructed, the evidence suggests the existence of incomplete lineage sorting or hybridization in the populations from Chiapas and Oaxaca assigned to Sergey tzeltal sp. n. PMID- 27408540 TI - A taxonomic review of the centipede genus Scolopendra Linnaeus, 1758 (Scolopendromorpha, Scolopendridae) in mainland Southeast Asia, with description of a new species from Laos. AB - The centipede genus Scolopendra in mainland Southeast Asia is reviewed taxonomically based on morphological characters, informed by a molecular phylogenetic analysis using sequences from three mitochondrial and nuclear genes (COI, 16S rRNA and 28S rRNA). Eight nominal species of Scolopendra, namely Scolopendra morsitans Linnaeus, 1758, Scolopendra subspinipes Leach, 1816, Scolopendra dehaani Brandt, 1840, Scolopendra multidens Newport, 1844, Scolopendra calcarata Porat, 1876, Scolopendra japonica Koch, 1878, Scolopendra pinguis Pocock, 1891, and Scolopendra dawydoffi Kronmuller, 2012, are redescribed together with some revision of type materials. Geographical variation in each species has been compiled with reference to samples that span their distribution ranges in Southeast Asia and some parts of neighbouring areas such as East Asia, the Indian Ocean, and Africa. Comparative study of traditional taxonomic characters from external morphology provides further information to distinguish some closely related species. Scolopendra cataracta Siriwut, Edgecombe & Panha, sp. n., is described from the southern part of Laos, with additional records in Thailand and Vietnam. The phylogenetic framework for Southeast Asian Scolopendra recognizes Scolopendra calcarata + Scolopendra pinguis, Scolopendra morsitans, and a Scolopendra subspinipes group that unites the other six species as the main clades. Within the Scolopendra subspinipes group, two monophyletic groups can be distinguished by having either slender or short, thick ultimate leg prefemora and different numbers of apical spines on the coxopleuron. Scolopendra arborea Lewis, 1982, is placed in subjective synonymy with Scolopendra dehaani. A survey of external morphology of the genital segments confirms its potential for improving species identification in Scolopendra. Some observations on biology and behaviour are recorded based on field surveys in this area. PMID- 27408541 TI - A revision of Chilicola (Heteroediscelis), a subgenus of xeromelissine bees (Hymenoptera, Colletidae) endemic to Chile: taxonomy, phylogeny, and biogeography, with descriptions of eight new species. AB - The bee subgenus Chilicola (Heteroediscelis) Toro & Moldenke, 1979 (Hymenoptera, Colletidae, Xeromelissinae) is revised. The subgenus is considered endemic to Chile and occurs across a broad range of habitats. Eight new species are described: Chilicola (Heteroediscelis) charizard Monckton, sp. n., Chilicola (Heteroediscelis) curvapeligrosa Monckton, sp. n., Chilicola (Heteroediscelis) guanicoe Monckton, sp. n., Chilicola (Heteroediscelis) katherinae Monckton, sp. n., Chilicola (Heteroediscelis) lickana Monckton, sp. n., Chilicola (Heteroediscelis) mayu Monckton, sp. n., Chilicola (Heteroediscelis) packeri Monckton, sp. n., and Chilicola (Heteroediscelis) randolphi Monckton, sp. n. One of the existing species, Chilicola (Heteroediscelis) valparaiso Toro & Moldenke, 1979, syn. n., is treated as a junior synonym of Chilicola (Heteroediscelis) mantagua Toro & Moldenke, 1979, and the nine remaining valid species are redescribed. Thoroughly illustrated keys to species for males and females are provided, along with habitus images, images of male terminalia, distribution maps for each species, and a map of relevant Chilean biogeographic regions. Results of phylogenetic analyses are presented, based upon 74 morphological characters and on CO1 barcode sequences, analyzed both separately and as a combined dataset. Monophyly of the subgenus is supported, and groupings within the subgenus are discussed in light of a biogeographic analysis of their species distributions (spatial analysis of vicariance), whereby divergence between taxa is found to occur primarily via north-south disjunctions. PMID- 27408542 TI - The family Plectopylidae (Gastropoda, Pulmonata) in Laos with the description of two new genera and a new species. AB - Previously only a single plectopylid species, Helix laomontana L. Pfeiffer, 1862 was reported from Laos. Here we erect Naggsia Pall-Gergely & Muratov, gen. n. for Helix laomontana based on the description of its reproductive anatomy and radula. Another species, Hunyadiscus saurini Pall-Gergely, gen. & sp. n. is described from Northern Laos based on conchological data. Helix (Plectopylis) andersoni Blanford, 1869, which is known from the Burmese-Chinese border region, is also classified within Hunyadiscus Pall-Gergely, gen. n. A third species, Gudeodiscus (Gudeodiscus) messageri raheemi Pall-Gergely & Hunyadi, 2015 is reported from Laos for the first time. The new localities represent the westernmost sites of the genus Gudeodiscus. The reproductive anatomy of the latter species is described. PMID- 27408543 TI - Granopupa in Iran, monophyly, and the fossil Granariinae (Gastropoda, Pulmonata, Chondrinidae). AB - Indisputable Chondrinidae, Granariinae species, characterized by shell shape and apertural dentition, are known from Eocene deposits to the Recent. The generic classification of the extant species is based on conchological, anatomical and molecular data that are available now for most of the known species, including 'Granaria' persica as a representative of the once problematic group of so-called eastern Granaria species. According to molecular and anatomical characters, these eastern species have to be classified with Granopupa granum in Granopupa. Graniberia gen. n. is introduced for Granaria braunii on the basis of molecular and conchological data. For the pre-Pleistocene species, two generic names are equally well available now, viz. Granopupa and Granaria. Shell characters only do not enable a decision here. For the sake of nomenclatorial stability we propose to use Granaria for these species. Because both molecular and anatomical data most likely will never be known for the fossils, it will remain unclear whether the combined extant and extinct Granaria species form a monophyletic group. PMID- 27408544 TI - Redescription of poorly known species of Ceratothoa Dana, 1852 (Crustacea, Isopoda, Cymothoidae), based on original type material. AB - Due to the difficulty in accurately identifying cymothoids, these parasitic isopods are often incorrectly named or confused with other species. Within the genus Ceratothoa, a number of recent studies have aimed at clarifying some of the problematic species; however, several of the less studied species still require revision. This paper redescribes, from type material, several poorly known Ceratothoa species including Ceratothoa angulata, Ceratothoa capri, Ceratothoa carinata, Ceratothoa collaris, Ceratothoa gilberti, Ceratothoa gobii, Ceratothoa guttata, Ceratothoa italica, Ceratothoa oestroides, and Ceratothoa verrucosa, further resolving taxonomic uncertainties within the genus. PMID- 27408545 TI - A new species of Acetalius Sharp from eastern China (Coleoptera, Staphylinidae, Pselaphinae). AB - The genus Acetalius Sharp currently contains two species from Japan. In this paper, a third species, Acetalius grandis Yin & Li, sp. n., is described from eastern China. The foveal pattern of Acetalius, and polymorphism and major diagnostic features of Acetalius grandis are figured. An updated key to Acetalius species is provided. PMID- 27408546 TI - Possible living fossil in Bolivia: A new genus of flea beetles with modified hind legs (Coleoptera, Chrysomelidae, Galerucinae, Alticini). AB - A new genus (Chanealtica) with three new species (Chanealtica cuevas, Chanealtica ellimon, and Chanealtica maxi) from Bolivia is described and illustrated. It is compared with Aphthonoides Jacoby, 1885, Argopistes Motschulsky, 1860, Metroserrapha Bechyne, 1958, Psylliodes Berthold, 1827 and Psyllototus Nadein, 2010. Remarkably, based on the available characters, among all the flea beetles, Chanealtica is mostly similar to an extinct genus Psyllototus. A discussion of diversity and function of the hind leg in flea beetles is provided. PMID- 27408547 TI - A DNA barcode library for ground beetles (Insecta, Coleoptera, Carabidae) of Germany: The genus Bembidion Latreille, 1802 and allied taxa. AB - As molecular identification method, DNA barcoding based on partial cytochrome c oxidase subunit 1 (COI) sequences has been proven to be a useful tool for species determination in many insect taxa including ground beetles. In this study we tested the effectiveness of DNA barcodes to discriminate species of the ground beetle genus Bembidion and some closely related taxa of Germany. DNA barcodes were obtained from 819 individuals and 78 species, including sequences from previous studies as well as more than 300 new generated DNA barcodes. We found a 1:1 correspondence between BIN and traditionally recognized species for 69 species (89%). Low interspecific distances with maximum pairwise K2P values below 2.2% were found for three species pairs, including two species pairs with haplotype sharing (Bembidion atrocaeruleum/Bembidion varicolor and Bembidion guttula/Bembidion mannerheimii). In contrast to this, deep intraspecific sequence divergences with distinct lineages were revealed for two species (Bembidion geniculatum/Ocys harpaloides). Our study emphasizes the use of DNA barcodes for the identification of the analyzed ground beetles species and represents an important step in building-up a comprehensive barcode library for the Carabidae in Germany and Central Europe as well. PMID- 27408548 TI - Reconstructing the historical distribution of the Amur Leopard (Panthera pardus orientalis) in Northeast China based on historical records. AB - The range of the Amur leopard (Panthera pardus orientalis) has decreased dramatically over the last 100 years. This species is still under extreme risk of extinction and conservation efforts are rigorous. Understanding the long-term dynamics of the population decline would be helpful to offer insight into the mechanism behind the decline and endangerment and improve conservation perspectives and strategies. Historical data collection has been the challenge for reconstructing the historical distribution. In China, new gazetteers having systematic compilation and considerable local ecological data can be considered as an important complementary for reconstruction. Therefore, we have set up a data set (mainly based on the new gazetteers) in order to identify the historical range of the Amur Leopard from the 1950s to 2014. The result shows that the Amur leopard was historically widely distributed with large populations in Northeastern China, but it presented a sharp decline after the 1970s. The decline appeared from the plains to the mountains and northeast to southwest since the 1950s. Long-term historical data, mainly from new gazetteers, demonstrates that such resources are capable of tracking species change through time and offers an opportunity to reduce data shortage and enhance understanding in conservation. PMID- 27408549 TI - A new, genetically divergent species of Pseudobaikalia Lindholm, 1909 (Caenogastropoda, Baicaliidae). AB - A new gastropod species, Pseudobaikalia michelae Sitnikoiva & Kovalenkova, sp. n., (family Baicaliidae) is described from Lake Baikal. This is the first new species from the Baicaliidae for forty years. The new species is distinguished from its sister taxa by means of comparative morphology as well as analyses of DNA sequences (mtDNA and an intron of alpha-subunit gene of ATP-synthase). It was found in the southern and central-eastern parts of the lake where it occurs sympatrically with three other baicaliid species. Characters of the female reproductive system (i.e., a long oviduct loop with 2-3 narrow tube-like evaginations) and the aperture (i.e., oval shape with a simple outer lip) place these snails in the genus Pseudobaikalia Lindholm, 1909. The new species is most similar in its shell morphology to the northern Baikal species Pseudobaikalia jentteriana (smooth elongated shape) but differs by a more oval aperture that is slightly angled to the columella. Combined mitochondrial and nuclear sequences in a Bayesian analysis showed that all specimens of Pseudobaikalia michelae sp. n. form a well-supported clade. PMID- 27408550 TI - Species limits in polymorphic mimetic Eniclases net-winged beetles from New Guinean mountains (Coleoptera, Lycidae). AB - Species delimitation was compared in a group of closely related lineages of aposematically colored Eniclases (Coleoptera, Lycidae) using morphology, genetic distances, and Bayesian implementation of the Poisson Tree Processes model. A high diversity of net-winged beetles was found in previously unsampled regions of New Guinea and ten new species are described: Eniclases bicolor sp. n., Eniclases bokondinensis sp. n., Eniclases brancuccii sp. n., Eniclases elelimensis sp. n., Eniclases infuscatus sp. n., Eniclases niger sp. n., Eniclases pseudoapertus sp. n., Eniclases pseudoluteolus sp. n., Eniclases tikapurensis sp. n., and Eniclases variabilis sp. n. Different levels of genetic and morphological diversification were identified in various sister-species pairs. As a result, both morphological and molecular analyses are used to delimit species. Sister-species with uncorrected pairwise genetic divergence as low as 0.45% were morphologically distinct not only in color pattern, but also in the relative size of eyes. Conversely, differences in color pattern regardless of their magnitude did not necessarily indicate genetic distance and intraspecific mimicry polymorphism was common. Additionally, genetic divergence without morphological differentiation was detected in one sister-species pair. Low dispersal propensity, diverse mimicry patterns, and mimetic polymorphism resulted in complex diversification of Eniclases and uncertain species delimitation in recently diversified lineages. PMID- 27408551 TI - Rediscovery and redescription of Dilobitarsus pendleburyi (Coleoptera, Elateridae, Agrypninae) from Southeast Asia. AB - Dilobitarsus pendleburyi Fleutiaux, 1934 is recorded for the first time after its original description and is redescribed. This represents the first record from the Malay Peninsula, Malaysia and Sumatra, Indonesia. The systematic position of this species is discussed. PMID- 27408552 TI - Two new species and new provincial records of aleocharine rove beetles from Newfoundland and Labrador, Canada (Coleoptera, Staphylinidae, Aleocharinae). AB - Two new species, Atheta pseudovestita Klimaszewski & Langor, sp. n., Silusa prettyae Klimaszewski & Langor, sp. n., are described, and 16 new provincial records, including one new country record, of aleocharine beetles are presented for the province of Newfoundland and Labrador. Diagnostics, images of habitus and genital structures, distribution, bionomics information and new locality data are provided for the newly recorded species. A new checklist with 189 species of aleocharines recorded from the province is presented. PMID- 27408553 TI - Fanniidae (Diptera): new synonym, new records and an updated key to males of European species of Fannia. AB - Based on revision of large recent collections of the authors, the following five species are first recorded from the Czech Republic: Fannia collini d'Assis Fonseca, 1966 (simultaneously first record in Central Europe), Fannia lugubrina (Zetterstedt, 1838), Fannia melania (Dufour, 1839), Fannia slovaca Gregor & Rozkosny, 2005, and Fannia brinae Albuquerque, 1951 (simultaneously first record from low altitudes). Another species, Fannia alpina Pont, 1970, is first recorded from Slovak Republic, and Fannia cothurnata (Loew, 1873) is first recorded from Kazakhstan. An updated key to males of European species of Fannia is presented. A list of Czech and Slovak Fanniidae is appended. One new synonym is established: Fannia lucida Chillcott, 1961 is considered junior synonym of Fannia norvegica Ringdahl, 1934. Altogether two species are first recorded from Bohemia [Fannia cothurnata (Loew, 1873) and Fannia vespertilionis Ringdahl, 1934] and three for Moravia [Fannia alpina Pont, 1970, Fannia conspecta Rudzinski, 2003, and Fannia limbata (Tiensuu, 1938) - this species considered in Central Europe very rare was found in numbers near waters both running and standing in early spring under unusually warm temperature conditions]. PMID- 27408554 TI - Amphibians and reptiles of the state of Coahuila, Mexico, with comparison with adjoining states. AB - We compiled a checklist of the amphibians and reptiles of the state of Coahuila, Mexico. The list comprises 133 species (24 amphibians, 109 reptiles), representing 27 families (9 amphibians, 18 reptiles) and 65 genera (16 amphibians, 49 reptiles). Coahuila has a high richness of lizards in the genus Sceloporus. Coahuila has relatively few state endemics, but has several regional endemics. Overlap in the herpetofauna of Coahuila and bordering states is fairly extensive. Of the 132 species of native amphibians and reptiles, eight are listed as Vulnerable, six as Near Threatened, and six as Endangered in the IUCN Red List. In the SEMARNAT listing, 19 species are Subject to Special Protection, 26 are Threatened, and three are in Danger of Extinction. Coahuila is home to several species of conservation concern, especially lizards and turtles. Coahuila is an important state for the conservation of the native regional fauna. PMID- 27408555 TI - Two new species of frogs of the genus Pristimantis from Llanganates National Park in Ecuador with comments on the regional diversity of Ecuadorian Pristimantis (Anura, Craugastoridae). AB - We describe two new species of frogs of the genus Pristimantis from the eastern slopes of the Ecuadorian Andes, at Parque Nacional Llanganates. The new species are characterized by the spiny appearance typical of several species inhabiting montane forests. Pristimantis yanezi sp. n. is most similar to Pristimantis colonensis and Pristimantis incanus but differs from both in groin coloration and by having smaller tubercles on the upper eyelids, heels, and tarsus. Pristimantis llanganati sp. n. is most similar to Pristimantis eriphus and Pristimantis chloronotus. It can be distinguished from Pristimantis eriphus by the color pattern on the scapular region and by having smaller conical tubercles on the dorsum. Pristimantis chloronotus differs from Pristimantis llanganati sp. n. in having a pair of sinuous paravertebral folds. Both new species occur in a region with few amphibian collections and nothing is known about their abundance and ecology. Therefore, it is recommended to assign them to the Data Deficient Red List category. Updated figures of species richness of Pristimantis among biogeographic regions in Ecuador are also presented. Pristimantis reach their highest diversity in Montane Forests of the eastern versant of the Andes. Its species richness across regions cannot be explained by regional area, elevation, temperature, or precipitation. Political endemism in Pristimantis is higher than that of other terrestrial vertebrates. PMID- 27408556 TI - A new substance to relax polychaete worms (Annelida) prior to morphological study. AB - A variety of chemical substances have been used to relax and/or immobilize polychaete worms, and other invertebrates, prior to specimen preparation for morphological examination. To solve difficulties encountered during the study of nereidid polychaetes (Annelida: Phyllodocida), an experiment was designed and carried out to investigate a new relaxing agent to immobilize nereidid specimens and stimulate pharynx eversion. The new substance, Dentol(r) (Khoraman laboratory, Iran), a dental anesthetic and antiseptic medicine containing 10% Carvacrol as the effective ingredient, was used for the first time and compared with other substances that have been used traditionally in polychaete studies. Crosstab analysis showed significant differences between different treatment groups, with Dentol(r) providing much better results for all considered criteria. PMID- 27408557 TI - A new family Lepidocharontidae with description of Lepidocharon gen. n., from the Great Barrier Reef, Australia, and redefinition of the Microparasellidae (Isopoda, Asellota). AB - Lepidocharontidae Galassi & Bruce, fam. n. is erected, containing Lepidocharon Galassi & Bruce, gen. n. and two genera transferred from the family Microparasellidae Karaman, 1934: Microcharon Karaman, 1934 and Janinella Albuquerque, Boulanouar & Coineau, 2014. The genus Angeliera Chappuis & Delamare Deboutteville, 1952 is placed as genus incertae sedis in this family. The Lepidocharontidae is characterised by having rectangular or trapezoidal somites in dorsal view, a single free pleonite, a tendency to reduction of the coxal plates, and the unique uropodal morphology of a large and long uropodal protopod on which the slender uropodal exopod articulates separately and anteriorly to the endopod. Lepidocharon Galassi & Bruce, gen. n. has a 6-segmented antennula, a well-developed antennal scale (rudimentary exopod), long and slender pereiopods 1 7 directed outwards, coxal plates rudimentary, incorporated to the lateral side of the sternites, not discernible in dorsal view, the single pleonite narrower than pereionite 7, scale-like elements bordering the proximal part of male pleopod 1 on posterior side, and stylet-guiding grooves of male pleopod 1 which run parallel to the outer lateral margins of the same pleopod. Lepidocharon priapus Galassi & Bruce, sp. n., type species for the genus, and Lepidocharon lizardensis Galassi & Bruce, sp. n. are described from Lizard Island, northern Great Barrier Reef. The most similar genus is Microcharon, both genera sharing the same general organization of the male pleopods 1 and 2, topology and architecture of the stylet-guiding groove of male pleopod 1, morphology of female operculum, presence of 2 robust claws of different lengths on pereiopodal dactylus 1-7, not sexually dimorphic. Lepidocharon gen. n. differs from Microcharon in the shape of the pereionites, very reduced coxal plates, the presence of imbricate scale-like elements bordering the proximal postero-lateral margins of the male pleopod 1, and the topology of the pereiopods, which are ventro-laterally inserted and directed outwards in Lepidocharon gen. n. and dorso laterally inserted and directed ventrally in Microcharon. Lepidocharon shares with the genus Janinella the morphology of the tergites and the reduced lacinia mobilis of the left mandible, but differs significantly from Janinella in having a well-developed antennal scale, very reduced coxal plates also in females bearing oostegites, the general morphology and spatial arrangement of the stylet guiding groove of male pleopod 1 and the possession of a 6-segmented antennula. The family Microparasellidae is redefined as monotypic, the only genus being Microparasellus Karaman, 1933. PMID- 27408558 TI - Two new species of Echinoderes (Kinorhyncha, Cyclorhagida), E. romanoi sp. n. and E. joyceae sp. n., from the Gulf of Mexico. AB - Meiofauna sampling on the continental shelf of the northern Gulf of Mexico has been ongoing since 2007, on annual cruises in collaboration with the National Marine Fisheries Service laboratory in Pascagoula, Mississippi. This sampling has resulted in numerous new species of kinorhynchs from the shelf sediment, two of which are described in detail in this paper. Other species descriptions from this research effort include Echinoderes augustae, Echinoderes skipperae, and Echinoderes charlotteae. We now describe Echinoderes romanoi sp. n. and Echinoderes joyceae sp. n., which are unique in their spine, tube, and glandular cell outlet patterns. PMID- 27408560 TI - A review of the sarawakensis species group of the ground beetle genus Orthogonius MacLeay, 1825 (Coleoptera, Carabidae, Orthogoniini). AB - The sarawakensis species group of the termitophilous carabid genus Orthogonius MacLeay, 1825 is defined and reviewed. Members of this species group are distributed in Southeast Asia and represented by four species, including two new species: Orthogonius sabahicus sp. n. (Sabah, northern Borneo, Malaysia) and Orthogonius morvanianus sp. n. (southern Thailand). A key to all species of the species group is also provided. PMID- 27408559 TI - The phylogenetic position of a new species of Plakobranchus from West Papua, Indonesia (Mollusca, Opisthobranchia, Sacoglossa). AB - Plakobranchus papua Meyers-Munoz & van der Velde, sp. n. from West Papua (Papua Barat province, Indonesia), is described based on its external morphology, colour pattern, internal anatomy, radula and reproductive system. In a molecular phylogenetic study specimens of this new species were compared with those of ten candidate taxa under the name Plakobranchus ocellatus van Hasselt, 1824. DNA analyses of COI mtDNA showed a clear distinction between Plakobranchus papua sp. n. and "Plakobranchus ocellatus". Plakobranchus papua, sp. n. also differed from all taxa that have been synonymised with Plakobranchus ocellatus. The genus is in dire need of taxonomic revision, preferably based on an integrative analysis involving morphology and DNA of all known Plakobranchus varieties. PMID- 27408561 TI - Caloparyphus palaearcticus sp. n. (Diptera, Stratiomyidae), the first record for the soldier fly genus in the Palaearctic. AB - Caloparyphus palaearcticus sp. n. is described from Russia and two localities in Mongolia and is the first representative of this genus in the Palaearctic and the only species found outside the New World. The morphological characters of the species are described and illustrated, and relationships to related species of Caloparyphus are discussed. PMID- 27408562 TI - Amphibians and Reptiles of the state of Nuevo Leon, Mexico. AB - We compiled a check list of the herpetofauna of Nuevo Leon. We documented 132 species (23 amphibians, 109 reptiles), representing 30 families (11 amphibians, 19 reptiles) and 73 genera (17 amphibians, 56 reptiles). Only two species are endemic to Nuevo Leon. Nuevo Leon contains a relatively high richness of lizards in the genus Sceloporus. Overlap in the herpetofauna of Nuevo Leon and states it borders is fairly extensive. Of 130 native species, 102 are considered species of Least Concern in the IUCN red list, four are listed as Vulnerable, five are listed as Near Threatened, and four are listed as Endangered. According to SEMARNAT, 78 species are not of conservation concern, 25 are subject to Special Protection, 27 are Threatened, and none are listed as in Danger of Extinction. Given current threats to the herpetofauna, additional efforts to understand the ecology and status of populations in Nuevo Leon are needed. PMID- 27408563 TI - A new species of Pristimantis (Amphibia, Anura, Craugastoridae) from the foothills of the Andes in Manu National Park, southeastern Peru. AB - We describe a new species of Pristimantis from the humid sub-montane forest of the Region Cusco in Peru. Pristimantis pluvialis sp. n. was collected in the Kosnipata and Entoro valleys at elevations from 740 to 1110 m a.s.l., near the borders of Manu National Park and within the Huachiperi Haramba Queros Conservation Concession. The new species can be distinguished from other members of the genus Pristimantis by its rostral tubercle, smooth dorsal skin, and by its advertisement call. Pristimantis lacrimosus and Pristimantis waoranii superficially most resemble the new species, but Pristimantis pluvialis sp. n. differs from both species by having a rostral tubercle (absent in Pristimantis waoranii and variable in Pristimantis lacrimosus) and larger size, from Pristimantis lacrimosus by its call emitted at a lower frequency, and from Pristimantis waoranii for its dorsal coloration with dark markings. Two other species have partially overlapping distributions and resemble the new species, Pristimantis mendax and Pristimantis olivaceus, but they produce advertisement calls with much higher dominant frequencies than the advertisement call of the new species. Furthermore, Pristimantis mendax differs from the new species by lacking a rostral tubercle and by having a sigmoid inner tarsal fold, whereas Pristimantis olivaceus differs by being smaller and by having dorsal skin shagreen with scattered tubercles. The new species has snout-vent length of 21.8 26.9 mm in males (n = 12) and 28.8 mm in a single female. PMID- 27408564 TI - Uncitermes almeriae, a new termite species from Amazonia (Isoptera, Termitidae, Syntermitinae). AB - The Neotropical termite genus Uncitermes Rocha & Cancello, 2012 was known from a single species, Uncitermes teevani (Emerson, 1925). In this paper a new species, Uncitermes almeriae sp. n., is described and illustrated from worker and soldier castes, along with observations on the Uncitermes nest. A distribution map with the occurrences of both species is presented. The new species is distinguished from its congener by the presence of short bristles covering the head capsule and frontal tube. PMID- 27408565 TI - A new erythroneurine leafhopper genus from Thailand (Hemiptera, Cicadellidae, Typhlocybinae), with description of three new species. AB - A new genus of tribe Erythroneurini from Thailand, Thaioneura gen. n., including three new species: Thaioneura nigrilinea sp. n. (type species), Thaioneura sinuata sp. n. and Thaioneura suphanburia sp. n., is described and illustrated and a key to species is provided. The new genus exhibits a pattern of interspecific variation in the hind wing venation that has not been observed in other genera of the tribe. PMID- 27408566 TI - A taxonomic account of the genus Stenodynerus from China, with descriptions of five new species (Hymenoptera, Vespidae, Eumeninae). AB - In this paper, 20 species of the genus Stenodynerus are reviewed and identified from China, including five new species: Stenodynerus ninglangensis Ma & Li, sp. n., Stenodynerus reflexus Ma & Li, sp. n., Stenodynerus similibaronii Ma & Li, sp. n., Stenodynerus strigatus Ma & Li, sp. n., and Stenodynerus tenuilamellatus Ma & Li, sp. n., and five new records: Stenodynerus baronii Giordani Soika, Stenodynerus bluethgeni van der Vecht, Stenodynerus picticrus (Thomson), Stenodynerus pullus Gusenleitner and Stenodynerus nepalensis Giordani Soika. The five new species are described and illustrated in detail. Moreover, the diagnostic characters of all new records and known species from China are provided, with a key to the Chinese species of Stenodynerus. PMID- 27408567 TI - Notes on the genus Episcaphium Lewis (Coleoptera, Staphylinidae, Scaphidiinae) with description of a new species from China. AB - A new Episcaphium species collected from Yunnan Province of China is described as Episcaphium zhuxiaoyui sp. n., and its diagnostic characters are illustrated. A new province record of Episcaphium haematoides is reported. A key to the Episcaphium species recorded from China is provided. PMID- 27408568 TI - A revision of the Stenus flammeus group (Coleoptera, Staphylinidae) with descriptions of twelve new species. AB - The Stenus flammeus group is proposed and twelve new species of the group are described: Stenus corniculus sp. n., Stenus daicongchaoi sp. n., Stenus jiajinshanus sp. n., Stenus jindingianus sp. n., Stenus paraflammeus sp. n., Stenus pengzhongi sp. n., Stenus pseudoflammeus sp. n., Stenus punctidorsus sp. n., Stenus tuyueyei sp. n., Stenus xilingmontis sp. n., and Stenus zhoudeyaoi sp. n. from Sichuan Province, and Stenus dabashanus sp. n. from Shaanxi Province. Their diagnostic characters are illustrated and a key to species of the group is provided. PMID- 27408570 TI - Two new species of Brachytrycherus Arrow, 1920 from China (Coleoptera, Endomychidae). AB - Two new species of Brachytrycherus from China, Brachytrycherus conaensis sp. n. and Brachytrycherus curviantennae sp. n. are described and illustrated. Brachytrycherus conaensis sp. n. is the first species of the Handsome Fungus Beetles recorded feeding on Ascomycetes. A key to the species of Brachytrycherus known in China is provided. PMID- 27408569 TI - Predaceous water beetles (Coleoptera, Hydradephaga) of the Lake St Lucia system, South Africa: biodiversity, community ecology and conservation implications. AB - Water beetles are one of the dominant macroinvertebrate groups in inland waters and are excellent ecological indicators, reflecting both the diversity and composition of the wider aquatic community. The predaceous water beetles (Hydradephaga) make up around one-third of known aquatic Coleoptera and, as predators, are a key group in the functioning of many aquatic habitats. Despite being relatively well-known taxonomically, ecological studies of these insects in tropical and subtropical systems remain rare. A dedicated survey of the hydradephagan beetles of the Lake St Lucia wetlands (South Africa) was undertaken between 2013 and 2015, providing the first biodiversity census for this important aquatic group in the iSimangaliso Wetland Park, a UNESCO World Heritage Site within the Maputaland biodiversity hotspot. A total of 32 sites covering the entire spectrum of waterbody types were sampled over the course of three collecting trips. The Lake St Lucia wetlands support at least 68 species of Hydradephaga, a very high level of diversity comparing favourably with other hotspots on the African continent and elsewhere in the world and a number of taxa are reported for South Africa for the first time. This beetle assemblage is dominated by relatively widespread Afrotropical taxa, with few locally endemic species, supporting earlier observations that hotspots of species richness and centres of endemism are not always coincident. Although there was no significant difference in the number of species supported by the various waterbody types sampled, sites with the highest species richness were mostly temporary depression wetlands. This contrasts markedly with the distribution of other taxa in the same system, such as molluscs and dragonflies, which are most diverse in permanent waters. Our study is the first to highlight the importance of temporary depression wetlands and emphasises the need to maintain a variety of wetland habitats for aquatic conservation in this biodiverse region. PMID- 27408571 TI - Assessment of the current state of biodiversity data for butterflies and skippers in the state of Mato Grosso, Brazil (Lepidoptera, Papilionoidea and Hesperioidea). AB - Lepidoptera is one of the four megadiverse insect orders, comprising butterflies and moths. In Brazil, the bulk of knowledge about the butterfly fauna is restricted to some areas in the southeast of the country, with large gaps of knowledge in other areas. The state of Mato Grosso is one of the largest states in Brazil, and holds three of the main Brazilian biomes: Amazon rain forest, Cerrado and Pantanal. However, knowledge about Mato Grosso butterflies is fragmented and restricted to a few localities, and information is scattered in various sources. The aim of this study is to assemble the biodiversity information of the butterfly fauna of the state of Mato Grosso based on historical and recent literature data and collections carried out in the southwest of the state from 2007-2009. Records without precise locality data or taxonomic information were not included. Species identification was based on literature and comparison with specimens in collections; higher and species-level taxonomy were updated based on the Neotropical Checklist of Hesperioidea and Papilionoidea and recent phylogenetic and revisionary taxonomic works. In total, 901 species were recorded in 2,820 occurrence records. This represents 148 species of Hesperiidae, 29 Papilionidae, 28 Pieridae, 77 Lycaenidae, 238 Riodinidae, and 381 Nymphalidae. Of these, 207 species records are from the type specimens of species described in the state. Based on the results and literature records for other Brazilian states and biomes, probably the figures for Mato Grosso are underestimated, particularly in the families Hesperiidae, Lycaenidae and Riodinidae, in that order. Future collecting efforts should be directed towards certain areas of the state, especially in less sampled areas and biomes, as the north of the state and Pantanal. PMID- 27408572 TI - The present state of the leech fauna (Annelida, Hirudinea) in the Upper Irtysh cascade of water reservoirs. AB - Hirudinea is a small and ecologically important group of aquatic organisms. However, up to date, the leech fauna of Kazakhstan is poorly studied. The presence of large under-collected areas, such as the Upper Irtysh basin, makes biodiversity studies concerning these invertebrates from Kazakhstan relevant. In this paper, the latest information on species diversity of the freshwater hirudofauna of the Upper Irtysh cascade of water reservoirs, the Kazakhstan part of Irtysh River, is presented. It includes 10 free-living and parasitic species, of which 7 and 9 inhabit the Shulbinsk and the Bukhtarma reservoirs, respectively. These species belong to 2 orders, 3 families and 6 genera. The faunal list highlights four potentially new morphological species (Alboglossiphonia sp., Erpobdella sp., Piscicola sp. 1 and Piscicola sp. 2). Besides them, another three species Erpobdella vilnensis, Helobdella stagnalis and Theromyzon tessulatum recorded for the first time in the area. The exact systematic position is stated for all leech taxa. Each species from the list accompanied with information on taxonomic synonymy, data on its geographic distribution, and brief summary of morphological and ecological characteristics. PMID- 27408573 TI - A new species of the genus Castoponera (Araneae, Corinnidae) from Sarawak, Borneo, with comparison to a related species. AB - A new species of the genus Castoponera Deeleman-Reinhold, 2001, Castoponera christae sp. n., is described here. The species is closely related to Castoponera lecythus Deeleman-Reinhold, 2001, but can be distinguished by the structures of the male palp and the female genitalia. PMID- 27408574 TI - Sinolatindia petila gen. n. and sp. n. from China (Blattodea, Corydiidae, Latindiinae). AB - Sinolatindia petila gen. n. and sp. n. (Blattodea: Corydiidae: Latindiinae) is reported from Yunnan Province, China. Description, illustrations and a distribution map of the new taxon are provided. Comparisons with the type genus Latindia Stal, 1860 and the genus Homopteroidea Shelford, 1906 are given. PMID- 27408575 TI - Cryptotermes colombianus a new drywood termite and distribution record of Cryptotermes in Colombia. AB - A new species of drywood termite (Kalotermitidae), Cryptotermes colombianus, is described and new records for Cryptotermes cylindroceps and Cryptotermes mangoldi are presented from the Caribbean coast of Colombia. Cryptotermes colombianus is described from two soldiers and genetic sequences. This unusual species differs noticeably from other regional Cryptotermes species for its weak and inconspicuous definition of the frontal and genal horns and its acute angle of the frons with respect to the vertex. Cryptotermes colombianus clustered with species from the Ethiopian and Oriental region and it is closely related to Cryptotermes havilandi. Cryptotermes cylindroceps is widely distributed along the Colombian Caribbean coast, commonly associated with dead wood in mangrove habitats. It also is commonly found in wooden furniture, constituting an important household pest. Cryptotermes mangoldi is reported from the Caribbean mainland for the first time. With these new records, there are now five Cryptotermes species for Colombia, including the pest species Cryptotermes brevis and Cryptotermes dudleyi. This new description raises the numbers of Neotropical Cryptotermes to a total of 34 species, of which 2 are fossils, 4 introduced, and 28 endemic. PMID- 27408576 TI - DNA Barcoding of genus Hexacentrus in China reveals cryptic diversity within Hexacentrus japonicus (Orthoptera, Tettigoniidae). AB - DNA barcoding has been proved successful to provide resolution beyond the boundaries of morphological information. Hence, a study was undertaken to establish DNA barcodes for all morphologically determined Hexacentrus species in China collections. In total, 83 specimens of five Hexacentrus species were barcoded using standard mitochondrial cytochrome c oxidase subunit I (COI) gene. Except for Hexacentrus japonicus, barcode gaps were present in the remaining Hexacentrus species. Taxon ID tree generated seven BOLD's barcode index numbers (BINs), four of which were in agreement with the morphological species. For Hexacentrus japonicus, the maximum intraspecific divergence (4.43%) produced a minimal overlap (0.64%), and 19 specimens were divided into three different BINs. There may be cryptic species within the current Hexacentrus japonicus. This study adds to a growing body of DNA barcodes that have become available for katydids, and shows that a DNA barcoding approach enables the identification of known Hexacentrus species with a very high resolution. PMID- 27408577 TI - Revision on Palaearctic species of Periclistus Forster with description of a new species and its host plant gall (Hymenoptera, Cynipidae). AB - Palaearctic species of Periclistus Forster has been systematically described, but a new inquiline gall-wasp, Periclistus qinghainensis sp. n., is described from China. This species was obtained from an unknown stem gall induced on Rosa sp. Diagnosis, distribution and biology of the new species are described in this paper. After examining the types of Periclistus idoneus Belizin, 1973 and Periclistus capillatus Belizin, 1968, it is concluded that Periclistus idoneus belongs to genus Aulacidea, and Periclistus capillatus is a valid species of Periclistus. A key to the Palaearctic Periclistus species is also given. PMID- 27408578 TI - Description of a new species of Aphanogmus Thomson (Hymenoptera, Ceraphronidae) that parasitizes acarivorous gall midges of Feltiella (Diptera, Cecidomyiidae) in Japan. AB - In 2008-2009, we reared small ceraphronids (about 0.5 mm in body length) from cocoons that had been made possibly by two acarivorous species, Feltiella acarisuga (Vallot) and Feltiella acarivora (Zehntner) (Diptera: Cecidomyiidae) in Okinawa, Japan. Detailed morphological observation revealed that the ceraphronid was a new species of Aphanogmus Thomson (Hymenoptera: Ceraphronidae). We describe it as Aphanogmus flavigastris Matsuo, sp. n. Identification of the Aphanogmus species is essential to evaluate its possibly negative effects on the predatory activity of Feltiella species that have been used as control agents against tetranychid mites. PMID- 27408579 TI - Revision of the Gonioctena nivosa species-group (Coleoptera, Chrysomelidae, Chrysomelinae) in the Holarctic region, with descriptions of two new species. AB - The Gonioctena nivosa species-group of the genus Gonioctena Chevrolat, 1836 is defined and reviewed. It contains six species including two new to science: Gonioctena gracilicornis (Kraatz, 1879), Gonioctena nivosa (Suffrian, 1851), Gonioctena norvegica (Strand, 1936), Gonioctena springlovae (Bechyne, 1948), Gonioctena amurensis Cho & Borowiec, sp. n. and Gonioctena jani Cho & Borowiec, sp. n. Six new synonyms are proposed: Gonioctena nivosa (= Gonioctena arctica alberta Brown, 1952, syn. n., Phytodecta linnaeana bergrothi Jacobson, 1901, syn. n., Phytodecta linnaeanus var. mutatus Achard, 1924, syn. n., Phytodecta linnaeanus var. simplex Achard, 1924, syn. n. and Phytodecta nivosa var. cedehensis Ronchetti, 1922, syn. n.) and Gonioctena norvegica (= Gonioctena janovskii Medvedev, 1976, syn. n.). Phytodecta flavicornis var. limbatipennis Achard, 1924 and Phytodecta nivosa var. bicolor Heyden, 1883 are removed from synonymy with Gonioctena nivosa (Suffrian, 1851) and are synonymized with Gonioctena flavicornis (Suffrian, 1851). Distribution maps, a key to species, color variation, geographic variation of male genitalia and host plants are provided. Ovoviviparity is newly recorded in Gonioctena gracilicornis and Gonioctena nivosa. Lectotypes are designated for Gonioctena affinis, Gonioctena arctica, Gonioctena linnaeana bergrothi and Gonioctena nivosa. PMID- 27408580 TI - PCR primers for 30 novel gene regions in the nuclear genomes of Lepidoptera. AB - We report primer pairs for 30 new gene regions in the nuclear genomes of Lepidoptera that can be amplified using a standard PCR protocol. The new primers were tested across diverse Lepidoptera, including nonditrysians and a wide selection of ditrysians. These new gene regions give a total of 11,043 bp of DNA sequence data and they show similar variability to traditionally used nuclear gene regions in studies of Lepidoptera. We feel that a PCR-based approach still has its place in molecular systematic studies of Lepidoptera, particularly at the intrafamilial level, and our new set of primers now provides a route to generating phylogenomic datasets using traditional methods. PMID- 27408581 TI - Varicus lacerta, a new species of goby (Teleostei, Gobiidae, Gobiosomatini, Nes subgroup) from a mesophotic reef in the southern Caribbean. AB - We describe a new species of goby, Varicus lacerta sp. n., which was collected from a mesophotic reef at Curacao, southern Caribbean. The new species is the tenth species of Varicus, all of which occur below traditional SCUBA depths in the wider Caribbean area. Its placement in the genus Varicus is supported by a molecular phylogenetic analysis of three nuclear genes and the mitochondrial gene cytochrome b. In addition, the new species has one anal-fin pterygiophore inserted anterior to the first haemal spine, which distinguishes Varicus species from most species in the closely related and morphologically similar genus Psilotris. Varicus lacerta sp. n. is distinguished from all other named species of Varicus by the absence of scales, having highly branched, feather-like pelvic fin rays, and in its live coloration. We provide the cytochrome c oxidase I DNA barcode of the holotype and compare color patterns of all species of Varicus and Psilotris for which color photographs or illustrations are available. This study is one of several recent studies demonstrating the utility of manned submersibles in exploring the diversity of poorly studied but species-rich deep-reef habitats. PMID- 27408582 TI - Editorial. PMID- 27408583 TI - High-throughput biodiversity analysis: Rapid assessment of species richness and ecological interactions of Chrysomelidae (Coleoptera) in the tropics. AB - Biodiversity assessment has been the focus of intense debate and conceptual and methodological advances in recent years. The cultural, academic and aesthetic impulses to recognise and catalogue the diversity in our surroundings, in this case of living objects, is furthermore propelled by the urgency of understanding that we may be responsible for a dramatic reduction of biodiversity, comparable in magnitude to geological mass extinctions. One of the most important advances in this attempt to characterise biodiversity has been incorporating DNA-based characters and molecular taxonomy tools to achieve faster and more efficient species delimitation and identification, even in hyperdiverse tropical biomes. In this assay we advocate for a broad understanding of Biodiversity as the inventory of species in a given environment, but also the diversity of their interactions, with both aspects being attainable using molecular markers and phylogenetic approaches. We exemplify the suitability and utility of this framework for large scale biodiversity assessment with the results of our ongoing projects trying to characterise the communities of leaf beetles and their host plants in several tropical setups. Moreover, we propose that approaches similar to ours, establishing the inventories of two ecologically inter-related and species-rich groups of organisms, such as insect herbivores and their angiosperm host-plants, can serve as the foundational stone to anchor a comprehensive assessment of diversity, also in tropical environments, by subsequent addition of trophic levels. PMID- 27408584 TI - Barcoding Chrysomelidae: a resource for taxonomy and biodiversity conservation in the Mediterranean Region. AB - The Mediterranean Region is one of the world's biodiversity hot-spots, which is also characterized by high level of endemism. Approximately 2100 species of leaf beetle (Coleoptera; Chrysomelidae) are known from this area, a number that increases year after year and represents 5/6% of the known species. These features, associated with the urgent need to develop a DNA-based species identification approach for a broad spectrum of leaf beetle species, prompted us to develop a database of nucleotide sequences, with a solid taxonomic background, for all the Chrysomelidae Latreille, 1802 sensu latu inhabiting the Mediterranean region. The Mediterranean Chrysomelidae Barcoding project, which has started in 2009, involves more than fifty entomologists and molecular biologists from different European countries. Numerous collecting campaigns have been organized during the first seven years of the project, which led to the collection of more than 5000 leaf beetle specimens. In addition, during these collecting campaigns two new allochthonous species for Europe, namely Ophraella communa LeSage, 1986 and Colasposoma dauricum Mannerheim, 1849, were intercepted and some species new to science were discovered (e.g., Pachybrachis sassii Montagna, 2011 and Pachybrachis holerorum Montagna et al., 2013). DNA was extracted from 1006 specimens (~13% of the species inhabiting the Mediterranean region) and a total of 910 cox1 gene sequences were obtained (PCR amplification efficiency of 93.8%). Here we report the list of the barcoded subfamilies, genera and the number of species for which cox1 gene sequences were obtained; the metadata associated with each specimen and a list of problematic species for which marker amplification failed. In addition, the nucleotide divergence within and between species and genera was estimated and values of intraspecific nucleotide divergence greater than the average have been discussed. Cryptocephalus quadripunctatus G. A. Olivier, 1808, Cryptocephalus rugicollis G. A. Olivier, 1791 and Exosoma lusitanicum Linnaeus, 1767) are representatives of these cases. PMID- 27408585 TI - Natural history of Javeta pallida Baly, 1858 on Phoenix palms in India (Chrysomelidae, Cassidinae, Coelaenomenoderini). AB - Members of the Old World hispine tribe, Coelaenomenoderini, are documented on host plants of Arecaceae, Cyperaceae, and Zingiberales. A few species are renowned pests of oil palm, especially in Africa. The host plants and natural history of Javeta pallida Baly, 1858, the only Indian species of the tribe, is reported for the first time. These beetles can densely infest indigenous wild date palms, Phoenix sylvestris (L.) Roxb. (Arecaceae), and also use the introduced date palm, Phoenix dactylifera L., which is an expanding crop in India. Javeta females lay single eggs and cover each with an ootheca. All larval stages mine the leaves and pupation occurs within the larval mine. Adults are exophagous, leaving linear feeding trenches. Natural and induced infestations of Javeta pallida on these two palms were observed and the potential of Javeta pallida as a pest of date palm in India is discussed. Javeta pallida completed development on Phoenix palms in 52-88 days (mean 66.38 days) with egg period 11 15 days (mean 12.8 days), larval period 21-54 days (mean 33.02 days) and pupal period 17-23 days (mean 20.52 days). Elasmus longiventris Verma and Hayat and Pediobius imbreus Walker (Hymenoptera: Eulophidae) parasitize the larva and pupa of Javeta pallida. PMID- 27408586 TI - Revision of the legume-feeding leaf beetle genus Madurasia Jacoby, including a new species description (Coleoptera, Chrysomelidae, Galerucinae, Galerucini). AB - Madurasia Jacoby is revised and Madurasia andamanica sp. n., endemic to the Andaman Islands in the Indian Ocean, is described and illustrated. Madurasia obscurella Jacoby, syn. n., is a new junior synonym of Madurasia undulatovittata (Motschulsky), comb. n. A lectotype is designated for Madurasia obscurella. Literature on the biology and management of Madurasia undulatovittata is reviewed. PMID- 27408587 TI - Spatial and environmental correlates of species richness and turnover patterns in European cryptocephaline and chrysomeline beetles. AB - Despite some general concordant patterns (i.e. the latitudinal richness gradient), species richness and composition of different European beetle taxa varies in different ways according to their dispersal and ecological traits. Here, the patterns of variation in species richness, composition and spatial turnover are analysed in European cryptocephaline and chrysomeline leaf beetles, assessing their environmental and spatial correlates. The underlying rationale to use environmental and spatial variables of diversity patterns is to assess the relative support for niche- and dispersal-driven hypotheses. Our results show that despite a broad congruence in the factors correlated with cryptocephaline and chrysomeline richness, environmental variables (particularly temperature) were more relevant in cryptocephalines, whereas spatial variables were more relevant in chrysomelines (that showed a significant longitudinal gradient besides the latitudinal one), in line with the higher proportion of flightless species within chrysomelines. The variation in species composition was also related to environmental and spatial factors, but this pattern was better predicted by spatial variables in both groups, suggesting that species composition is more linked to dispersal and historical contingencies than species richness, which would be more controlled by environmental limitations. Among historical factors, Pleistocene glaciations appear as the most plausible explanation for the steeper decay in assemblage similarity with spatial distance, both in cryptocephalines and chrysomelines. PMID- 27408588 TI - Two new oribatid mites from the Republic of Rwanda. Plasmobates zarae sp. n. (Acari, Plasmobatidae) and Basilobelba spasmenosi sp. n. (Acari, Basilobelbidae). AB - Two new species of oribatid mites, Plasmobates zarae sp. n. and Basilobelba spasmenosi sp. n. are described from the Republic of Rwanda. They can easily be differentiated from other species by a number of characters. Plasmobates zarae sp. n. is differentiated the following characters. four types of particular cerotegumental layers. Integument slightly foveate to smooth on prodorsum; foveate on notogaster; ventral region rugose to smooth.Large rostral setae inserted on protuberance, whip-shaped, with longitudinal pucker; interlamellar setae rod-shaped with triangular scales; interlamellar setae small. Medial band on prodorsum extending to anterior of central part, but not reaching rostrum. Bothridium horn-shaped; opening basally incised with rectilinear wall, internal bothridial rings dentate. Sensillus whip-like, with minute triangular scales. Variably distributed circumgastric macropores. Opisthosomal gland apophysis flat, triangular in lateral view and cylindrical in posterolateral view. Six pairs of notogastral setae, all situated posterior to opisthosomal gland level. Aggenital setae not detected; three pairs of adanal setae; two pairs of anal setae present. Nymphal scalps simple without anterior tuft or filaments, with dentate peripheral ridge. Larval scalp shaped like Chinese hat. Basilobelba spasmenosi sp. n. is characterized by the combination of the following characters: Cerotegument: thick basal layer with amorphous coat and cavities of different sizes, as well as structures resembling small cauliflowers. Setation: simple: notogastral, epimeral, genital, anal; simple long, basally barbate: le, ro setae; simple, whip shaped: ex setae; medium length, sharpened tip with thorns on surface: in setae, leg setae; Flabellate: setae situated in ventral neotrichous zone. Thorn-like barbs and more or less parallel longitudinal grooves present on body surface of le, ro, in and leg setae. Prodorsum: rostrum finger-shaped, relative sizes of setae: le > ro > in > ex. Prodorsal cuticular surface smooth with shallow transversal furrow and two oblique furrows determining two triangular structures. Large humpbacked CSO situated anterior to and in medial line with in setal insertion, dorsal bothridial opening. Notogaster swollen, hemispheric; nine pairs of minute setae, only h1 , h2 , h3 easily identifiable, cuticular wart and dimple clearly visible. Humeral apophysis with longitudinal furrow dorsally. Elongate chelicera with cha, chb setae, behind them a series of scales directed dorsoventrally. Epimeral setation 3-1-3-3, adanal-aggenital neotrichy with between 8-10 setae. Nymphal scalps with very particular bean-shaped structure on either side of the decoupage zone, surrounding horn-like structure. Scalps with cuticular polyhedral reticulate to ovoid structure, often forming a cavity, either completely perforated or with a thin cuticular layer resembling an interior membrane. PMID- 27408589 TI - The genus Paraplonobia Wainstein and Neopetrobia Wainstein (Acari, Trombidiformes, Tetranychidae) from Saudi Arabia: new species, new records and key to the world species of Paraplonobia. AB - The two tetranychid genera Paraplonobia Wainstein and Neopetrobia Wainstein (Trombidiformes: Tetranychidae) are reported for the first time from Saudi Arabia. Three new species Paraplonobia (Anaplonobia) arabica Mirza & Alatawi, sp. n., Paraplonobia (Anaplonobia) haloxylonia Alatawi & Mirza, sp. n. and Paraplonobia (Anaplonobia) tabukensis Kamran & Alatawi, sp. n. are described and illustrated based on adult females, collected from Prosopis juliflora (SW.) Dc. (Fabaceae) and Haloxylon salicornicum Bunge (Amaranthaceae) from two different regions of Saudi Arabia. Neopetrobia mcgregori (Pritchard and Baker) is redescribed and illustrated based on female collected from Cynodon dactylon L. (Poaceae).The diagnostic morphological features including leg chaetotaxy of all known species of the subgenus Anaplonobia is tabulated. A key to the world species of the genus Paraplonobia is also provided. PMID- 27408590 TI - Redescription of Gammarus pseudosyriacus (Karaman & Pinkster, 1977) and description of a new subspecies from southern Iran (Crustacea, Amphipoda, Gammaridae). AB - The present study focused on redescription of Gammarus pseudosyriacus (Karaman & Pinkster, 1977) based on new materials from Zagros Mountains and describes a new subspecies of freshwater amphipod, Gammarus pseudosyriacus issatisi subsp. n., from the southern Zagros Mountains. The work is based on morphological and morphometric comparisons. This new subspecies has features similar to Gammarus pseudosyriacus. The distinct features that distinguish Gammarus pseudosyriacus issatisi subsp. n. from Gammarus pseudosyriacus are the smaller eyes, shorter body length, and shorter flagellum of antenna 1 and 2. PMID- 27408591 TI - Morphological features of larvae of Drusus plicatus Radovanovic (Insecta, Trichoptera) from the Republic of Macedonia with molecular, ecological, ethological, and distributional notes. AB - A description of the larva of Drusus plicatus Radovanovic is given for the first time. The most important diagnostic characters enabling separation from larvae of the other Drusinae from the southeast Europe are listed. Molecular, ecological, and ethological features and distribution patterns of the species are given. Additionally, information on the sympatric caddisfly species of the three springs where larvae and adults of Drusus plicatus were found and presented. PMID- 27408592 TI - New species of Goniocolletes and Trichocolletes (Hymenoptera, Colletidae) from southern Australia. AB - Goniocolletes comatus Maynard, 2013 is redescribed. Goniocolletes wanni sp. n. and the male of Trichocolletes luteorufus Batley & Houston, 2012 are described. PMID- 27408593 TI - Review of the Fannia postica-group Chillcott, 1961 of the genus Fannia Robineau Desvoidy, 1830, with description of two new species from the Palearctic and Oriental regions (Diptera, Fanniidae). AB - A total of 17 species of the Fannia postica-group Chillcott, 1961 from the Palearctic and Oriental regions are reviewed herein, 2 of which are described from China as new: Fannia ningxiaensis Wang & Zhang, sp. n. and Fannia subaethiops Wang & Zhu, sp. n.. Fannia labidocerca Feng & Xue, 2006, originally placed in Fannia serena-group Chillcott, 1961, is moved to the postica-group and re-described. An identification key to the males of known species from these regions is provided. PMID- 27408594 TI - Description of a new catfish genus (Siluriformes, Loricariidae) from the Tocantins River basin in central Brazil, with comments on the historical zoogeography of the new taxon. AB - This study presents the description of a new genus of the catfish subfamily Neoplecostominae from the Tocantins River basin. It can be distinguished from other neoplecostomine genera by the presence of (1) three hypertrophied bicuspid odontodes on the lateral portion of the body (character apparently present in mature males); (2) a large area without odontodes around the snout; (3) a post dorsal ridge on the caudal peduncle; (4) a straight tooth series in the dentary and premaxillary rows; (5) the absence of abdominal plates; (6) a conspicuous series of enlarged papillae just posterior to the dentary teeth; and (7) caudal peduncle ellipsoid in cross section. We used maximum likelihood and Bayesian methods to estimate a time-calibrated tree with the published data on 116 loricariid species using one nuclear and three mitochondrial genes, and we used parametric biogeographic analyses (DEC and DECj models) to estimate ancestral geographic ranges and to infer the colonization routes of the new genus and the other neoplecostomines in the Tocantins River and the hydrographic systems of southeastern Brazil. Our phylogenetic results indicate that the new genus and species is a sister taxon of all the other members of the Neoplecostominae, originating during the Eocene at 47.5 Mya (32.7-64.5 Mya 95% HPD). The present distribution of the new genus and other neoplecostomines may be the result of a historical connection between the drainage basins of the Paraguay and Parana rivers and the Amazon basin, mainly through headwater captures. PMID- 27408595 TI - Taxonomic revision of the rock-dwelling door snail genus Montenegrina Boettger, 1877 (Mollusca, Gastropoda, Clausiliidae). AB - The genus Montenegrina is revised on the basis of material available at the Hungarian Natural History Museum (Budapest), Naturhistorisches Museum Wien (Vienna), and the Naturmuseum Senckenberg (Frankfurt am Main), as well as newly discovered populations. The following new taxa are described: Montenegrina haringae sp. n., Montenegrina lillae sp. n., Montenegrina prokletiana sp. n., Montenegrina sturanyana sp. n., Montenegrina grammica erosszoltani ssp. n., Montenegrina grammica improvisa ssp. n., Montenegrina hiltrudae desaretica ssp. n., Montenegrina hiltrudae selcensis ssp. n., Montenegrina laxa delii ssp. n., Montenegrina nana barinai ssp. n., Montenegrina prokletiana kovacsorum ssp. n., Montenegrina rugilabris golikutensis ssp. n., Montenegrina rugilabris gregoi ssp. n., Montenegrina skipetarica danyii ssp. n., Montenegrina skipetarica gurelurensis ssp. n., Montenegrina skipetarica pifkoi ssp. n., Montenegrina skipetarica puskasi ssp. n., Montenegrina sporadica tropojana ssp. n., Montenegrina sturanyana gropana ssp. n., Montenegrina sturanyana ostrovicensis ssp. n., and Montenegrina tomorosi hunyadii ssp. n. A neotype is designated for Montenegrina helvola (Kuster, 1860), and Montenegrina cattaroensis antivaricostata nom. n. was introduced to replace the junior homonym Clausilia umbilicata costata Boettger, 1907 (non Pfeiffer, 1928). Of each taxon types or specimens from the type localities are figured, and distribution maps are provided. PMID- 27408596 TI - Morphometric and molecular characterization of populations of Pratylenchus kumamotoensis and P. pseudocoffeae (Nematoda, Pratylenchidae) newly recorded in Korea. AB - At least 70 species of root-lesion nematodes, Pratylenchus spp., have been identified worldwide, many of which are serious pests of various agricultural crop plants. In Korea, only 14 species have been recorded in vegetable and fruit fields. Here, we report two new records of root-lesion nematode species in Korea based on morphometric and molecular methods. Soil samples were collected from chrysanthemum cultivars in various regions. Morphometric diagnosis showed that two new records for Korea: Pratylenchus kumamotoensis in Chilgok County and Pratylenchus pseudocoffeae in Geumsan County. In addition, molecular diagnosis using the two sequences of the internal transcribed spacer (ITS) and the D2-D3 region of ribosomal DNA showed that these two species were most similar with those from Japan, Costa Rica and USA. The similarities of the ITS and D2-D3 sequences were 99.85 and 99.74%, respectively, for Pratylenchus kumamotoensis and 99.99 with Costa Rica populations and 99.86% with USA populations, respectively, for Pratylenchus pseudocoffeae. To our knowledge, this is the first report of two species in Korea. PMID- 27408597 TI - Review of the western African millipede genus Diaphorodesmus Silvestri, 1896 (Diplopoda, Polydesmida, Chelodesmidae), with the description of a similar, but new monotypic genus from Cameroon. AB - The genus Diaphorodesmus is revised and shown to comprise only a single species, Diaphorodesmus dorsicornis (Porat, 1894) by priority, with the only other formal congener, Diaphorodesmus attemsii Verhoeff, 1938, considered as its junior subjective synonym, syn. n. A new monotypic genus, Diaphorodesmoides gen. n., is created to include Diaphorodesmoides lamottei sp. n., from southwestern Cameroon. Both these genera seem to be especially similar in sharing remarkable dorsal horns on metaterga 2-4, a unique synapomorphy in the basically Afrotropical subfamily Prepodesminae, family Chelodesmidae, to which they belong. In contrast to Diaphorodesmus which shows two, increasingly short, paramedian horns on each of metaterga 2-4, the ozopores borne on distinct porosteles, and the gonopod prefemoral process and solenophore less strongly elaborate, Diaphorodesmoides gen. n. has a single, increasingly large, central horn on each of metaterga 2-4, the ozopores opening flush dorsolaterally on the surface of poriferous paraterga, and both the gonopod prefemoral process and solenophore especially complex. The genus Campodesmoides VandenSpiegel, Golovatch & Nzoko Fiemapong, 2015, and its sole, and type, species Campodesmoides corniger VandenSpiegel, Golovatch & Nzoko Fiemapong, 2015, are transferred from Campodesmidae to Chelodesmidae and formally synonymized with Diaphorodesmus and Diaphorodesmus dorsicornis, both syn. n. PMID- 27408598 TI - New species and records of Uropodina mites from Iran (Acari, Mesostigmata). AB - In this paper, a new species of the genus Nenteria Oudemans, 1915 is described on the basis of adult female and male specimens collected in soil and litter in parks in Kerman, southeastern Iran, and Tehran, northern Iran. A key to the Iranian species of Nenteria is also presented, and Trachycilliba abantica (Bal & Ozkan, 2007) is reported for the first time in Iran. PMID- 27408599 TI - Description of a new troglomorphic species of Charinus Simon, 1892 from Brazil (Arachnida, Amblypygi, Charinidae). AB - Charinus taboa sp. n. comprises the twenty-second species of the genus described for Brazil. The new species belongs to the eastern Brazilian group, in which all species have sucker-like gonopods. Charinus taboa sp. n. has a marked sexual dimorphism in the pedipalps as do other members of the genus in the country. The description of Charinus taboa sp. n. offers an opportunity to discuss some aspects of ecology, troglomorphism and conservation within the genus. A key to the eastern Brazilian species of Charinus is provided. PMID- 27408600 TI - Three new spider species of the genus Pholcus from the Taihang Mountains of China (Araneae, Pholcidae). AB - In this study, three new species belonging to the genus Pholcus, collected from a forest of the Taihang Mountains, P. R. China, are described under the names of Pholcus papillatus sp. n. (male, female), Pholcus curvus sp. n. (male, female) and Pholcus auricularis sp. n. (male, female). PMID- 27408601 TI - A preliminary synopsis on amber scorpions with special reference to Burmite species: an extraordinary development of our knowledge in only 20 years. AB - A preliminary study on fossil scorpions found in amber, from the Lower Cretaceous through the Palaeocene and up to the Miocene is proposed. Scorpions remain rare among the arthropods found trapped in amber. Only 24 specimens are known from Cretaceous amber, representing eight families and subfamilies, ten genera and 21 species; in parallel, 10 specimens have been recorded from Baltic amber representing seven genera and ten species. A few more recent fossils from Dominican and Mexican amber have also been described. The present study of a new scorpion specimen from the Cretaceous amber of Myanmar (Burmite) resulted in the description of one new species, Betaburmesebuthus bellus sp. n. - belonging to the subfamily Palaeoburmesebuthinae Lourenco, 2015. The new description brings further elements to the clarification of the status of this subfamily, which is now raised to family level. Once again, this new Burmite element attests to the considerable degree of diversity in the Burmese amber-producing forests. PMID- 27408602 TI - Evemphyron sinense, a new genus and species infesting legume seedpods in China (Coleoptera, Attelabidae, Rhynchitinae). AB - A new genus Evemphyron Alonso-Zarazaga, Lv & Wang, gen. n., belonging to Attelabidae Rhynchitinae, is described. Its single species, Evemphyron sinense Alonso-Zarazaga, Lv & Wang, sp. n., was reared from larvae found inside seed pods of the legume Callerya dielsiana (Fabaceae, Millettieae) in Sichuan Province (China). The species is figured and placed in the Deporaini because of the presence of minute labial palpi, the strongly crescentic apex of the postmentum, and the apodemes of male IX sternite and female VIII sternite curved sinistro anterially near their cephalic end. It shows 3-segmented labial palpi and male sex patches on the procoxae, characters that suggest a basal position in the tribe. PMID- 27408603 TI - Further contributions to the Hydradephaga (Coleoptera, Haliplidae, Gyrinidae and Dytiscidae) fauna of Prince Edward Island, Canada: new records, distributions and faunal composition. AB - The Haliplidae, Gyrinidae and Dytiscidae (Coleoptera) of Prince Edward Island, Canada were surveyed during the years 2004-2005. A total of 2450 individuals from 79 species were collected from 98 different localities, among which 30 species are newly recorded from that region. Among these, Acilius sylvanus Hilsenhoff, Rhantus consimilis Motschulsky and Neoporus sulcipennis (Fall) stand out as representing the easternmost reports of these species in Canada. Once removed, Gyrinus aquiris LeConte (Gyrinidae) is reinstated in the faunal list of Prince Edward Island. According to this study and literature 84 species of Hydradephaga are currently known from Prince Edward Island. The Nearctic component of the fauna is made up of 68 species (80.9%) and the Holarctic component of 16 species (19.1%). Most species are characteristic of the Boreal and Atlantic Maritime Ecozones and have a transcontinental distribution. In an examination of the Hydradephaga of insular portions of Atlantic Canada, we found that despite significantly different land areas and different distances to the neighbouring continental mainland the island faunas of Prince Edward Island and insular Newfoundland are very similar in the number of species (84 and 94 species respectively) despite differences in composition. With a land area significantly larger than that of Prince Edward Island, however, the fauna of Cape Breton Island was 39% smaller consisting of 53 species. This difference could be due to the comparative lack of collecting efforts on Cape Breton Island. PMID- 27408604 TI - Species delimitation in the Grayling genus Pseudochazara (Lepidoptera, Nymphalidae, Satyrinae) supported by DNA barcodes. AB - The Palaearctic Grayling genus Pseudochazara encompasses a number of petrophilous butterfly species, most of which are local endemics especially in their centre of radiation in SW Asia and the Balkans. Due to a lack of consistent morphological characters, coupled with habitat induced variability, their taxonomy is poorly understood and species delimitation is hampered. We employed a DNA barcoding approach to address the question of separate species status for several European taxa and provide first insight into the phylogeny of the genus. Unexpectedly we found conflicting patterns with deep divergences between presumably conspecific taxa and lack of divergence among well-defined species. We propose separate species status for Pseudochazara tisiphone, Pseudochazara amalthea, Pseudochazara amymone, and Pseudochazara kermana all of which have separate well supported clades, with the majority of them becoming local endemics. Lack of resolution in the 'Mamurra' species group with well-defined species (in terms of wing pattern and coloration) such as Pseudochazara geyeri, Pseudochazara daghestana and Pseudochazara alpina should be further explored using nuclear molecular markers with higher genetic resolution. PMID- 27408605 TI - The collection of birds from Sao Tome and Principe at the Instituto de Investigacao Cientifica Tropical of the University of Lisbon (Portugal). AB - The former Instituto de Investigacao Cientifica Tropical-IICT (Lisbon, Portugal), recently integrated into the University of Lisbon, gathers important natural history collections from Portuguese-speaking African countries. In this study, we describe the bird collection from the Democratic Republic of Sao Tome and Principe, which was fully taxonomically checked and georeferenced. The IICT bird collection contains 5598 specimens, of which 559 are from Sao Tome and Principe, representing 85 taxa, including 19 endemic species and 13 endemic subspecies of birds. The specimens were collected between 1946 and 1973, although 43% of the records are from 1954 and 45% are from 1970. The geographic distribution of samples covers the whole territory, with a higher number of records from Sao Tome than from Principe. The districts with highest number of records are Pague (equivalent to Principe Island), and Agua Grande and Me-Zochi on Sao Tome. Despite the relatively low number of specimens per taxon, the importance of the collection is considerable due to the high number of endemic and threatened species represented. Furthermore, it adds valuable information to the GBIF network, especially for a country whose two islands are each an Endemic Bird Area and for which substantial gaps in ornithological knowledge remain. PMID- 27408606 TI - Summarizing health-related quality of life (HRQOL): development and testing of a one-factor model. AB - BACKGROUND: Health-related quality of life (HRQOL) is a multi-dimensional concept commonly used to examine the impact of health status on quality of life. HRQOL is often measured by four core questions that asked about general health status and number of unhealthy days in the Behavioral Risk Factor Surveillance System (BRFSS). Use of these measures individually, however, may not provide a cohesive picture of overall HRQOL. To address this concern, this study developed and tested a method for combining these four measures into a summary score. METHODS: Exploratory and confirmatory factor analyses were performed using BRFSS 2013 data to determine potential numerical relationships among the four HRQOL items. We also examined the stability of our proposed one-factor model over time by using BRFSS 2001-2010 and BRFSS 2011-2013 data sets. RESULTS: Both exploratory factor analysis and goodness of fit tests supported the notion that one summary factor could capture overall HRQOL. Confirmatory factor analysis indicated acceptable goodness of fit of this model. The predicted factor score showed good validity with all of the four HRQOL items. In addition, use of the one-factor model showed stability, with no changes being detected from 2001 to 2013. CONCLUSION: Instead of using four individual items to measure HRQOL, it is feasible to study overall HRQOL via factor analysis with one underlying construct. The resulting summary score of HRQOL may be used for health evaluation, subgroup comparison, trend monitoring, and risk factor identification. PMID- 27408607 TI - Future healthy life expectancy among older adults in the US: a forecast based on cohort smoking and obesity history. AB - BACKGROUND: In the past three decades, the elderly population in the United States experienced increase in life expectancy (LE) and disability-free life expectancy (LE(ND)), but decrease in life expectancy with disability (LE(D)). Smoking and obesity are two major risk factors that had negative impacts on these trends. While smoking prevalence continues to decline in recent decades, obesity prevalence has been growing and is currently at a high level. This study aims to forecast the healthy life expectancy for older adults aged 55 to 85 in the US from 2011 to 2040, in relation to their smoking and obesity history. METHODS: First, population-level mortality data from the Human Mortality Database (HMD) and individual-level disability data from the US National Health Interview Survey (NHIS) were used to estimate the transition rates between different health states from 1982 to 2010, using a multi-state life table (MSLT) model. Second, the estimated transition rates were fitted and projected up to 2040, using a modified Lee-Carter model that incorporates cohort smoking and obesity history from NHIS. RESULTS: Mortality and morbidity for both sexes will continue to decline in the next decades. Relative to 2010, men are expected to have 3.2 years gain in LE(ND) and 0.8 years loss in LE(D). For women, there will be 1.8 years gain in LE(ND) and 0.8 years loss in LE(D). By 2040, men and women are expected to spend respectively 80 % and 75 % of their remaining life expectancy between 55 and 85 disability-free. CONCLUSIONS: Smoking and obesity have independent negative impacts on both the survival and disability of the US older population in the coming decades, and are responsible for the present and future gender disparity in mortality and morbidity. Overall, the US older population is expected to enjoy sustained health improvements and compression of disability, largely due to decline in smoking. PMID- 27408608 TI - A systematic review and meta-analysis of carbohydrate benefits associated with randomized controlled competition-based performance trials. AB - BACKGROUND: Carbohydrate supplements are widely used by athletes as an ergogenic aid before and during sports events. The present systematic review and meta analysis aimed at synthesizing all available data from randomized controlled trials performed under real-life conditions. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched systematically up to February 2015. Study groups were categorized according to test mode and type of performance measurement. Subgroup analyses were done with reference to exercise duration and range of carbohydrate concentration. Random effects and fixed effect meta-analyses were performed using the Software package by the Cochrane Collaboration Review Manager 5.3. RESULTS: Twenty-four randomized controlled trials met the objectives and were included in the present systematic review, 16 of which provided data for meta-analyses. Carbohydrate supplementations were associated with a significantly shorter exercise time in groups performing submaximal exercise followed by a time trial [mean difference -0.9 min (95 % confidence interval -1.7, -0.2), p = 0.02] as compared to controls. Subgroup analysis showed that improvements were specific for studies administering a concentration of carbohydrates between 6 and 8 % [mean difference -1.0 min (95 % confidence interval -1.9, -0.0), p = 0.04]. Concerning groups with submaximal exercise followed by a time trial measuring power accomplished within a fixed time or distance, mean power output was significantly higher following carbohydrate load (mean difference 20.2 W (95 % confidence interval 9.0, 31.5), p = 0.0004]. Likewise, mean power output was significantly increased following carbohydrate intervention in groups with time trial measuring power within a fixed time or distance (mean difference 8.1 W (95 % confidence interval 0.5, 15.7) p = 0.04]. CONCLUSION: Due to the limitations of this systematic review, results can only be applied to a subset of athletes (trained male cyclists). For those, we could observe a potential ergogenic benefit of carbohydrate supplementation especially in a concentration range between 6 and 8 % when exercising longer than 90 min. PMID- 27408609 TI - Sellar reconstruction without intrasellar packing after endoscopic surgery of pituitary macroadenomas is better than its reputation. AB - OBJECTIVES: Sellar reconstruction with intrasellar packing following endoscopic resection of pituitary macroadenomas remains a subject of clinical and radiological discussion particularly, when an intraoperative cerebrospinal fluid (CSF) leakage is absent. This study was conducted to contribute our experience with sellar reconstruction after a standard endoscopic surgery of pituitary macroadenomas without intraoperative CSF leakage to the ongoing discussion between techniques with and without intrasellar packing. METHODS: A consecutive series of 47 pituitary macroadenomas undergoing excision via a standard endoscopic endonasal transsphenoidal surgery (EETS) without evident intraoperative CSF leakage were retrospectively evaluated over a 10-months mean follow-up period. According to the sellar reconstruction technique, three groups could be identified: Group A - with no intrasellar packing, Group B - with haemostatic materials packing, and Group C - with abdominal fat packing. Postoperative clinical and radiological assessments of the three groups were documented and analyzed for differences in outcome. RESULTS: Postoperative clinical assessment did not differ significantly between the three groups. In group A, postoperative CSF leakage, sphenoid sinusitis and empty sella syndrome were not observed. However, a significant difference in radiological assessment could be identified; the interpretation of sellar contents in postoperative MRI of group A succeeded earlier and more reliably than in other groups with intrasellar packing. CONCLUSIONS: There is no difference in the incidence of postoperative CSF leakage and empty sella syndrome among the various reconstructive techniques with and without intrasellar packing, irrespective of size and extension of the pituitary adenoma. Sellar reconstruction without intrasellar packing following a standard EETS is not inferior to other techniques with packing and even shows more radiological advantages, which made it our preferred technique, at least if no intraoperative CSF leakage is evident. PMID- 27408610 TI - Heat for wounds - water-filtered infrared-A (wIRA) for wound healing - a review. AB - BACKGROUND: Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and a low thermal load to the skin surface. wIRA corresponds to the major part of the sun's heat radiation, which reaches the surface of the Earth in moderate climatic zones filtered by water and water vapour of the atmosphere. wIRA promotes healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic cellular effects. METHODS: This publication includes a literature review with search in PubMed/Medline for "water-filtered infrared-A" and "wound"/"ulcus" or "wassergefiltertes Infrarot A" and "Wunde"/"Ulkus", respectively (publications in English and German), and additional analysis of study data. Seven prospective clinical studies (of these six randomized controlled trials (RCT), the largest study with n=400 patients) were identified and included. All randomized controlled clinical trials compare a combination of high standard care plus wIRA treatment vs. high standard care alone. The results below marked with "vs." present these comparisons. RESULTS: wIRA increases tissue temperature (+2.7 degrees C at a tissue depth of 2 cm), tissue oxygen partial pressure (+32% at a tissue depth of 2 cm) and tissue perfusion (effect sizes within the wIRA group). wIRA promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain (with respect to alleviation of pain, without any exception during 230 irradiations, 13.4 vs. 0.0 on a visual analogue scale (VAS 0 100), median difference between groups 13.8, 95% confidence interval (CI) 12.3/16.7, p<0.000001) with a substantially reduced need for analgesics (52-69% less in the three groups with wIRA compared to the three control groups in visceral surgery, p=0.000020 and 0.00037 and 0.0045, respectively; total of 6 vs. 14.5 analgesic tablets on 6 surveyed days (of weeks 1-6) in chronic venous stasis ulcers, median difference -8, 95% CI -10/-5, p=0.000002). Further effects are: Faster reduction of wound area (in severely burned children: 90% reduction of wound size after 9 vs. 13 days, after 9 days 89.2% vs. 49.5% reduction in wound area, median difference 39.5% wound area reduction, 95% CI 36.7%/42.2%, p=0.000011; complete wound closure of chronic venous stasis ulcers after 14 vs. 42 days, median difference -21 days, 95% CI -28/-10, p=0.000005). Better overall evaluation of wound healing (surgical wounds: 88.6 vs. 78.5 on a VAS 0-100, median difference 8.9, 95% CI 6.1/12.0, p<0.000001). Better overall evaluation of the effect of irradiation (79.0 vs. 46.8 on a VAS 0-100 with 50 as neutral point, median difference 27.9, 95% CI 19.8/34.6, p<0.000001). Higher tissue oxygen partial pressure during irradiation with wIRA (at a tissue depth of 2 cm 41.6 vs. 30.2 mmHg, median difference 11.9 mmHg, 95% CI 9.6/14.2 mmHg, p<0.000001). Higher tissue temperature during irradiation with wIRA (at a tissue depth of 2 cm 38.9 vs. 36.4 degrees C, median difference 2.6 degrees C, 95% CI 2.2/2.9 degrees C, p<0.000001). Better cosmetic result (84.5 vs. 76.5 on a VAS 0-100, median difference 7.9, 95% CI 3.7/12.0, p=0.00027). Lower wound infection rate (single preoperative irradiation: 5.1% vs. 12.1% wound infections in total, difference 7.0%, 95% CI -12.8%/-1.3%, p=0.017, of these: late wound infections (postoperative days 9-30) 1.7% vs. 7.7%, difference -6.0%, 95% CI -10.3%/-1.7%, p=0.007). Shorter hospital stay (9 vs. 11 postoperative days, median difference 2 days, 95% CI -3/0 days, p=0.022). Most of the effects have been proven with an evidence level of 1a or 1b. CONCLUSION: Water-filtered infrared-A is a useful complement for the treatment of acute and chronic wounds. PMID- 27408612 TI - Juvenile Atlantic cod behavior appears robust to near-future CO2 levels. AB - BACKGROUND: Ocean acidification caused by the anthropogenic release of CO2 is considered a major threat to marine ecosystems. One unexpected impact of elevated water CO2 levels is that behavioral alterations may occur in tropical reef fish and certain temperate fish species. These effects appear to alter many different types of sensory and cognitive functions; if widespread and persistent, they have the potential to cause ecosystem changes. METHODS: We investigated whether economically and ecologically important Atlantic cod also display behavioral abnormalities by exposing 52 juvenile cod to control conditions (500 MUatm, duplicate tanks) or an end-of-the-century ocean acidification scenario (1000 MUatm, duplicate tanks) for one month, during which time the fish were examined for a range of behaviors that have been reported to be affected by elevated CO2 in other fish. The behaviors were swimming activity, as measured by number of lines crossed per minute, the emergence from shelter, determined by how long it took the fish to exit a shelter after a disturbance, relative lateralization (a measure of behavioral turning side preference), and absolute lateralization (the strength of behavioral symmetry). RESULTS: We found no effect of CO2 treatment on any of the four behaviors tested: activity (F = 1.61, p = 0.33), emergence from shelter (F = 0.13, p = 0.76), relative lateralization (F = 2.82, p = 0.50), and absolute lateralization (F = 0.80, p = 0.26). CONCLUSION: Our results indicate that the behavior of Atlantic cod could be resilient to the impacts of near future levels of water CO2. PMID- 27408611 TI - Risk factors for unstructured treatment interruptions and association with survival in low to middle income countries. AB - BACKGROUND: Antiretroviral therapy (ART) treatment interruptions lead to poor clinical outcomes with unplanned or unstructured TIs (uTIs) likely to be underreported. This study describes; uTIs, their risk factors and association with survival. METHODS: Analysis of ART programmatic data from 11 countries across Asia and Africa between 2003 and 2013 where an uTI was defined as a >=90 day patient initiated break from ART calculated from the last day the previous ART prescription would have run out until the date of the next ART prescription. Factors predicting uTI were assessed with a conditional risk-set multiple failure time-to-event model to account for repeated events per subject. Association between uTI and mortality was assessed using Cox proportional hazards, with a competing risks extension to test for the influence of lost to follow-up (LTFU). RESULTS: 40,632 patients were included from 11 countries across 33 sites (17 Africa, 16 Asia). Median duration of follow-up was 1.61 years (IQR 0.54-3.31 years), 3386 (8.3 %) patients died, and 3453 (8.5 %) were LTFU. There were 14,817 uTIs, with 10,162 (25 %) patients having more than one uTI. In the adjusted model males were at lower risk of uTI (aHR 0.94, p < 0.01, and age 20-59 was protective compared to <20 years (20-39 years aHR 0.87, p < 0.01; 40-59 years aHR 0.86, p < 0.01). Preserved immune function, as measured by higher CD4 cell count, was associated with a reduced rate of uTI compared to CD4 <200 cells/MUL (CD4 200-350 cells/MUL aHR 0.89, p < 0.01; CD4 >350 cells/MUL aHR 0.87, p < 0.01), whereas advanced clinical disease was associated with increased uTI rate (WHO stage 3 aHR 1.10, p < 0.01; WHO stage 4 aHR 1.21, p < 0.01). There was no relationship between uTI and mortality after adjusting for disease status and considering LTFU as a competing risk. CONCLUSIONS: uTIs were frequent in people in ART programs in low-middle income countries and associated with younger age, female gender and advanced HIV. uTI did not predict survival when loss to follow-up was considered a competing risk. Further evaluation of uTI predictors and interventions to reduce their occurrence is warranted. PMID- 27408614 TI - The high cost of half-hearted breastfeeding promotion in Germany. AB - The economic value of breastfeeding to the society at large is under researched and its importance as a preventive public health strategy is underestimated. What little research there is indicates that considerable savings would accrue from following the WHO/UNICEF advice to breastfeed exclusively for six months and continue breastfeeding along with complementary foods for two years or more. Despite relatively high breastfeeding initiation in Germany, neither exclusive breastfeeding nor breastfeeding duration come close to international recommendations. Breastfeeding is mostly regarded as a woman's personal choice and the government has been slow to engage in breastfeeding promotion, support and research. Some structures in Germany do offer support for breastfeeding women - including the growing number of Baby Friendly Hospital Initiative (BFHI) certified hospitals and a comprehensive maternity leave policy. However, the costs of breastfeeding are mostly borne by the mothers and those for breastfeeding training mostly by the individual health care workers or hospital, while the health insurance companies and society-at-large are profiting from the financial savings from exclusive and long-term breastfeeding. Factors which might improve breastfeeding rates and duration in this country include broad expansion of and financial support for both BFHI hospitals as well as training for the health care personnel who support the mother-infant dyad during the breastfeeding period. PMID- 27408613 TI - Liver fat accumulation in response to overfeeding with a high-fat diet: a comparison between South Asian and Caucasian men. AB - BACKGROUND: South Asians were reported to have a higher liver fat content as compared to BMI-matched Caucasians. This study compared the increase in liver fat content in response to overfeeding with a high fat diet in South Asian and Caucasian men when matched for body fat percentage. METHODS: Ten South Asian men (BMI 18-29 kg/m(2)) and 10 Caucasian men (BMI 22-33 kg/m(2)), aged 20-40 y, matched for body fat percentage, were included. A weight maintenance diet was given for 3 days based on the individual energy requirement. Individual energy requirement of the subjects was calculated based on their body composition (measured by hydro densitometry and deuterium dilution) and activity counts (accelerometer). Liver fat content was measured before and after 4 days of overfeeding (50 % excess energy need) with a high fat diet (60 % energy from fat). Fat distribution was measured by anthropometry and an MRI scan of the abdomen while liver fat content using 1H-MRS. RESULTS: While having a similar body fat % (P = 0.58), South Asians had a lower BMI (P = 0.04) than Caucasians. Liver fat content at baseline did not differ between ethnicities (P = 0.48) and was associated with visceral fat area (P = 0.002, R(2) = 0.56) but not with ethnicity (P = 0.13). Overfeeding with a high fat diet significantly increased liver fat (P = 0.01) but the increase did not differ between ethnicities (P = 0.47). There was no difference in the total abdominal fat area (P = 0.37), subcutaneous abdominal fat area (P = 0.18) and visceral fat area (VAT, P = 0.32). However as a percentage of the total abdominal fat area, VAT was higher in South Asians (P = 0.003). CONCLUSION: Despite a relatively higher percentage of visceral fat area, liver fat increased similarly in South Asian and Caucasian men in response to overfeeding with a high fat diet. TRIAL REGISTRATION: The study was registered in the public trial registry www.ccmo.nl No. NL31217.068.10. PMID- 27408615 TI - Growth and stress response in Arabidopsis thaliana, Nicotiana benthamiana, Glycine max, Solanum tuberosum and Brassica napus cultivated under polychromatic LEDs. AB - BACKGROUND: The use of light emitting diodes (LEDs) brings several key advantages over existing illumination technologies for indoor plant cultivation. Among these are that LEDs have predicted lifetimes from 50-100.000 hours without significant drops in efficiency and energy consumption is much lower compared to traditional fluorescent tubes. Recent advances allow LEDs to be used with customized wavelengths for plant growth. However, most of these LED growth systems use mixtures of chips emitting in several narrow wavelengths and frequently they are not compatible with existing infrastructures. This study tested the growth of five different plant species under phosphor coated LED-chips fitted into a tube with a standard G13 base that provide continuous visible light illumination with enhanced blue and red light. RESULTS: The LED system was characterized and compared with standard fluorescence tubes in the same cultivation room. Significant differences in heat generation between LEDs and fluorescent tubes were clearly demonstrated. Also, LED lights allowed for better control and stability of preset conditions. Physiological properties such as growth characteristics, biomass, and chlorophyll content were measured and the responses to pathogen assessed for five plant species (both the model plants Arabidopsis thaliana, Nicotiana bentamiana and crop species potato, oilseed rape and soybean) under the different illumination sources. CONCLUSIONS: We showed that polychromatic LEDs provide light of sufficient quality and intensity for plant growth using less than 40% of the electricity required by the standard fluorescent lighting under test. The tested type of LED installation provides a simple upgrade pathway for existing infrastructure for indoor plant growth. Interestingly, individual plant species responded differently to the LED lights so it would be reasonable to test their utility to any particular application. PMID- 27408616 TI - Current status of acupuncture and moxibustion in China. AB - Acupuncture and moxibustion are more integrated in the Chinese healthcare system than in the national healthcare systems of other countries. Development of acupuncture and moxibustion in China is making progress in this field. For overseas researchers, this commentary offers perspectives on the current status of acupuncture and moxibustion in China and examines relevant opportunities and challenges in healthcare reforms. There has been a steady increase in the number of undergraduates and postgraduates studying acupuncture and moxibustion in Chinese Medicine (CM) universities in China over the past decade. The legislation of CM physicians that was established in 1999 and the launch of continuing medical education in CM in 2002 have ensured the basic competency of practitioners. The Chinese Government has also shown support for CM development by increasing investment in related fields of research and administration. New challenges have emerged as the healthcare landscape in China has evolved over the past decade. It is important to harness the potential of acupuncture and moxibustion to create a value-driven healthcare system that meets the health needs of a rapidly aging society. PMID- 27408618 TI - TagDigger: user-friendly extraction of read counts from GBS and RAD-seq data. AB - BACKGROUND: In genotyping-by-sequencing (GBS) and restriction site-associated DNA sequencing (RAD-seq), read depth is important for assessing the quality of genotype calls and estimating allele dosage in polyploids. However, existing pipelines for GBS and RAD-seq do not provide read counts in formats that are both accurate and easy to access. Additionally, although existing pipelines allow previously-mined SNPs to be genotyped on new samples, they do not allow the user to manually specify a subset of loci to examine. Pipelines that do not use a reference genome assign arbitrary names to SNPs, making meta-analysis across projects difficult. RESULTS: We created the software TagDigger, which includes three programs for analyzing GBS and RAD-seq data. The first script, tagdigger_interactive.py, rapidly extracts read counts and genotypes from FASTQ files using user-supplied sets of barcodes and tags. Input and output is in CSV format so that it can be opened by spreadsheet software. Tag sequences can also be imported from the Stacks, TASSEL-GBSv2, TASSEL-UNEAK, or pyRAD pipelines, and a separate file can be imported listing the names of markers to retain. A second script, tag_manager.py, consolidates marker names and sequences across multiple projects. A third script, barcode_splitter.py, assists with preparing FASTQ data for deposit in a public archive by splitting FASTQ files by barcode and generating MD5 checksums for the resulting files. CONCLUSIONS: TagDigger is open source and freely available software written in Python 3. It uses a scalable, rapid search algorithm that can process over 100 million FASTQ reads per hour. TagDigger will run on a laptop with any operating system, does not consume hard drive space with intermediate files, and does not require programming skill to use. PMID- 27408617 TI - H. pylori infection is related to mitochondrial microsatellite instability in gastric carcinogenesis. AB - BACHGROUND: To assess the correlation of H. pylori infection with mitochondrial microsatellite instability (mtMSI) and IL-8 in gastric carcinogenesis. METHODS: H. pylori infection was evaluated through histology and a urease breath test; mtMSI was measured using PCR-single strand conformation polymorphism (PCR-SSCP); IL-8 was analyzed with ELISA methods. RESULTS: The detection rate of mtMSI was significantly higher in specimens with H. pylori infection than in those without H. pylori infection (P < 0.05). The levels of IL-8 were significantly higher in specimens with mtMSI than in those without mtMSI (P < 0.01).An association of mtMSI with the intestinal histological type was found (P < 0.05). Increased IL-8 levels induced by H. pylori were related to the invasion, lymphnode spreading and clinical stage of gastric cancer (P < 0.05). CONCLUSIONS: H. pylori infection is related to mitochondrial microsatellite instability in the early steps of gastric cancer development. IL-8 may play a role in the development of mtMSI induced by H. pylori. Our results support a role for mtMSI in different mechanisms of gastric carcinogenesis. PMID- 27408619 TI - The Friendship Bench programme: a cluster randomised controlled trial of a brief psychological intervention for common mental disorders delivered by lay health workers in Zimbabwe. AB - BACKGROUND: Common mental disorders (CMD) are a leading cause of disability globally. Emerging evidence indicates that in low and middle income countries the treatment gap for CMD can be addressed through the use of trained and supervised lay health workers (LHWs). Few clinical trials have evaluated the use of such task-shifting approaches in sub-Saharan Africa. In Zimbabwe, we have successfully piloted a task-shifting intervention delivered by LHWs. This protocol describes a cluster randomised controlled trial to assess the effectiveness of this intervention. METHODS: Each of 24 randomly selected clinics from a pool of 42 in Harare will recruit 24 participants (N = 576). The clinics are randomised in a 1:1 ratio to receive either the intervention package [a problem solving therapy package delivered over a 4-6 week period by LHWs (N = 24) followed by a 6-week group support programme which focuses mainly on teaching a craft skill] or enhanced usual care, which includes usual care and psycho-education. Primary care attenders aged 18 years and above who score positive on a locally validated CMD screening questionnaire (Shona Symptom Questionnaire, SSQ-14) will be eligible for recruitment and asked for informed consent to participate in the trial. The primary measure is the SSQ score at 6 months. CONCLUSION: This effectiveness trial using LHWs to address the treatment gap for CMD will contribute to the body of knowledge on the feasibility and ability for scale-up of interventions for CMD. TRIAL REGISTRATION: PACTR201410000876178. PMID- 27408620 TI - Nonsuicidal self-injury: a condition for further study. PMID- 27408621 TI - Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration. AB - BACKGROUND: Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications. The effects of LV on target cells are expected to be limited to gene delivery. Yet, human hematopoietic CD34+ cells respond to functional LVs as well as several types of non-integrating LVs by genome-wide DNA methylation changes. RESULTS: A new algorithm for the analysis of 450K Illumina data showed that these changes were marked by de novo methylation. The same 4126 cytosines located in islands corresponding to 1059 genes were systematically methylated. This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette. Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response. CONCLUSION: These findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome. PMID- 27408623 TI - Pathotypes and probiotics: response to a commentary on the detection of a Shiga toxin producing Escherichia coli in a Crohn's disease patient. AB - A recent report on the detection in a Crohn's disease (CD) patient of an adherent and invasive Shiga toxin producing Escherichia coli (STEC) (Gut pathogens 2015, 7:2) prompted a commentary expressing some skepticism on the significance of the paper findings (Gut pathogens 2015, 7:15). Besides focusing on recurrent issues concerning the difficulties in defining a pathogen, the opinion considers recent data demonstrating the presence of virulence factors in a commercial probiotic. In response to the commentary's observations, additional information on the described STEC strain, as well as a short discussion on CD associated E. coli are presented here. PMID- 27408622 TI - Implementation of blinded outcome assessment in the Effective Verruca Treatments trial (EverT) - lessons learned. AB - BACKGROUND: Trials using inadequate levels of blinding may report larger effect sizes than blinded studies. It has been suggested that blinded outcome assessment in open trials may in some cases be undertaken by assessments of photographs. The aim of this paper is to explore the effect of using different methods to assess the primary outcome in the EVerT (Effective Verruca Treatments) trial. It also aims to give an overview of the experiences of using digital photographs within the trial. METHODS: We undertook a secondary analysis to explore the effect of using three different methods to assess the primary outcome in the EVerT trial: assessment of digital photographs by blinded healthcare professionals; blinded healthcare professional assessment at the recruiting site and patient self report. The verruca clearance rates were calculated using the three different methods of assessment. A Cohen's kappa measure of inter-rater agreement was used to assess the agreement between the methods. We also investigated the experiences of healthcare professionals using digital photographs within the trial. RESULTS: Digital photographs for 189 out of 240 (79 %) patients in the trial were received for outcome assessment. Of the 189 photographs, 30 (16 %) were uninterpretable. The overall verruca clearance rates were 21 % (43/202,) using the unblinded patient self-reported outcome, 6 % (9/159,) using blinded assessment of digital photographs and 14 % (30/210,) using blinded outcome assessment at the site. CONCLUSIONS: Despite differences in the clearance rates found using different methods of outcome assessment, this did not change the original conclusion of the trial, that there is no evidence of a difference in effectiveness between cryotherapy and salicylic acid. Future trials using digital photographs should consider individual training needs at sites and have a backup method of assessment agreed a priori. TRIAL REGISTRATION: ISRCTN Registry ISRCTN18994246. PMID- 27408624 TI - Comparative genomic analysis of Klebsiella pneumoniae subsp. pneumoniae KP617 and PittNDM01, NUHL24835, and ATCC BAA-2146 reveals unique evolutionary history of this strain. AB - BACKGROUND: Klebsiella pneumoniae subsp. pneumoniae KP617 is a pathogenic strain that coproduces OXA-232 and NDM-1 carbapenemases. We sequenced the genome of KP617, which was isolated from the wound of a Korean burn patient, and performed a comparative genomic analysis with three additional strains: PittNDM01, NUHL24835 and ATCC BAA-2146. RESULTS: The complete genome of KP617 was obtained via multi-platform whole-genome sequencing. Phylogenetic analysis along with whole genome and multi-locus sequence typing of genes of the Klebsiella pneumoniae species showed that KP617 belongs to the WGLW2 group, which includes PittNDM01 and NUHL24835. Comparison of annotated genes showed that KP617 shares 98.3 % of its genes with PittNDM01. Nineteen antibiotic resistance genes were identified in the KP617 genome: bla OXA-1 and bla SHV-28 in the chromosome, bla NDM-1 in plasmid 1, and bla OXA-232 in plasmid 2 conferred resistance to beta lactams; however, colistin- and tetracycline-resistance genes were not found. We identified 117 virulence factors in the KP617 genome, and discovered that the genes encoding these factors were also harbored by the reference strains; eight genes were lipopolysaccharide-related and four were capsular polysaccharide related. A comparative analysis of phage-associated regions indicated that two phage regions are specific to the KP617 genome and that prophages did not act as a vehicle for transfer of antimicrobial resistance genes in this strain. CONCLUSIONS: Whole-genome sequencing and bioinformatics analysis revealed similarity in the genome sequences and content, and differences in phage-related genes, plasmids and antimicrobial resistance genes between KP617 and the references. In order to elucidate the precise role of these factors in the pathogenicity of KP617, further studies are required. PMID- 27408627 TI - Breathe: exploring respiratory health and exercise. AB - The June issue of Breathe explores topics relating to respiratory health and exercise http://ow.ly/L3Zy300oWUN. PMID- 27408625 TI - Mechanism of spacer integration links the CRISPR/Cas system to transposition as a form of mobile DNA. AB - It has recently become clear that many bacterial and archaeal species possess adaptive immune systems. These are typified by multiple copies of DNA sequences known as clustered regularly interspaced short palindromic repeats (CRISPRs). These CRISPR repeats are the sites at which short spacers containing sequences of previously encountered foreign DNA are integrated, and the spacers serve as the molecular memory of previous invaders. In vivo work has demonstrated that two CRISPR-associated proteins - Cas1 and Cas2 - are required for spacer integration, but the mechanism by which this is accomplished remained unclear. Here we review a recent paper describing the in vitro reconstitution of CRISPR spacer integration using purified Cas1 and Cas2 and place the results in context of similar DNA transposition reactions and the crystal structure of the Cas1/Cas2 complex. PMID- 27408628 TI - Paediatric HERMES: European accreditation of training centres in paediatric respiratory medicine. AB - HERMES: European accreditation of training centres in paediatric respiratory medicine http://ow.ly/ZBmUg. PMID- 27408629 TI - Self-fill oxygen technology: benefits for patients, healthcare providers and the environment. AB - "Non-delivery" home oxygen technologies that allow self-filling of ambulatory oxygen cylinders are emerging. They can offer a relatively unlimited supply of ambulatory oxygen in suitably assessed people who require long-term oxygen therapy (LTOT), providing they can use these systems safely and effectively. This allows users to be self-sufficient and facilitates longer periods of time away from home. The evolution and evidence base of this technology is reported with the experience of a national service review in Scotland (UK). Given that domiciliary oxygen services represent a significant cost to healthcare providers globally, these systems offer potential cost savings, are appealing to remote and rural regions due to the avoidance of cylinder delivery and have additional lower environmental impact due to reduced fossil fuel consumption and subsequently reduced carbon emissions. Evidence is emerging that self-fill/non-delivery oxygen systems can meet the ambulatory oxygen needs of many patients using LTOT and can have a positive impact on quality of life, increase time spent away from home and offer significant financial savings to healthcare providers. EDUCATIONAL AIMS: Provide update for oxygen prescribers on options for home oxygen provision.Provide update on the evidence base for available self-fill oxygen technologies.Provide and update for healthcare commissioners on the potential cost-effective and environmental benefits of increased utilisation of self-fill oxygen systems. PMID- 27408630 TI - Dysfunctional breathing and reaching one's physiological limit as causes of exercise-induced dyspnoea. AB - KEY POINTS: Excessive exercise-induced shortness of breath is a common complaint. For some, exercise-induced bronchoconstriction is the primary cause and for a small minority there may be an alternative organic pathology. However for many, the cause will be simply reaching their physiological limit or be due to a functional form of dysfunctional breathing, neither of which require drug therapy.The physiological limit category includes deconditioned individuals, such as those who have been through intensive care and require rehabilitation, as well as the unfit and the fit competitive athlete who has reached their limit with both of these latter groups requiring explanation and advice.Dysfunctional breathing is an umbrella term for an alteration in the normal biomechanical patterns of breathing that result in intermittent or chronic symptoms, which may be respiratory and/or nonrespiratory. This alteration may be due to structural causes or, much more commonly, be functional as exemplified by thoracic pattern disordered breathing (PDB) and extrathoracic paradoxical vocal fold motion disorder (pVFMD).Careful history and examination together with spirometry may identify those likely to have PDB and/or pVFMD. Where there is doubt about aetiology, cardiopulmonary exercise testing may be required to identify the deconditioned, unfit or fit individual reaching their physiological limit and PDB, while continuous laryngoscopy during exercise is increasingly becoming the benchmark for assessing extrathoracic causes.Accurate assessment and diagnosis can prevent excessive use of drug therapy and result in effective management of the cause of the individual's complaint through cost-effective approaches such as reassurance, advice, breathing retraining and vocal exercises. This review provides an overview of the spectrum of conditions that can present as exercise- induced breathlessness experienced by young subjects participating in sport and aims to promote understanding of the need for accurate assessment of an individual's symptoms. We will highlight the high incidence of nonasthmatic causes, which simply require reassurance or simple interventions from respiratory physiotherapists or speech pathologists. PMID- 27408631 TI - Exercise training in idiopathic pulmonary fibrosis: is it of benefit? AB - KEY POINTS: Exercise training has been proven to be a safe and effective behavioural intervention for prevention and rehabilitation of chronic conditions.Despite the complexity of the signs and symptoms presented in IPF, supervised exercise training is a feasible and effective treatment for clinical improvement.Emerging data show significant enhancements in exercise capacity, dyspnoea and quality of life among IPF patients after exercise training interventions.Understanding of the principles of exercise training and the pathophysiology of IPF are essential for effective exercise programme delivery. EDUCATIONAL AIMS: To describe the current evidence supporting exercise training for IPF.To highlight the importance of exercise physiology principles in rehabilitation treatment of patients with IPF.To introduce an effective practical exercise programme for IPF.To discuss the possible underlying physiological mechanisms of training effects in IPF. Exercise is a well-documented safe and effective intervention for prevention and rehabilitation of chronic diseases. Idiopathic pulmonary fibrosis (IPF) is a chronic deadly lung disease associated with severe signs and symptoms, exercise intolerance, diminished quality of life and poor prognosis. In the short term, supervised exercise training programmes have demonstrated clinical benefits in improving exercise capacity, dyspnoea and quality of life in patients with IPF. The underlying mechanisms of chronic adaption to a regular exercise regimen in IPF have yet to be well described and require further investigation. The available data underscore the importance of implementing training principles to target the pathophysiological impairments of IPF in order to optimise training adaption and enhance the outcomes. The current exercise training data in IPF provide sufficient evidence of clinical benefit for consideration to be given to recommending exercise-based pulmonary rehabilitation as standard of care for IPF. PMID- 27408632 TI - Endurance training: is it bad for you? AB - EDUCATIONAL AIMS: To illustrate the characteristics of endurance exercise training and its positive effects on health.To provide an overview on the effects of endurance training on airway cells and bronchial reactivity.To summarise the current knowledge on respiratory health problems in elite athletes. Endurance exercise training exerts many positive effects on health, including improved metabol-ism, reduction of cardiovascular risk, and reduced all-cause and cardiovascular mortality. Intense endurance exercise causes mild epithelial injury and inflammation in the airways, but does not appear to exert detrimental effects on respiratory health or bronchial reactivity in recreational/non-elite athletes. Conversely, elite athletes of both summer and winter sports show increased susceptibility to development of asthma, possibly related to environmental exposures to allergens or poor conditioning of inspired air, so that a distinct phenotype of "sports asthma" has been proposed to characterise such athletes, who more often practise aquatic and winter sports. Overall, endurance training is good for health but may become deleterious when performed at high intensity or volume. PMID- 27408633 TI - The World Anti-Doping Code: can you have asthma and still be an elite athlete? AB - KEY POINTS: The World Anti-Doping Code (the Code) does place some restrictions on prescribing inhaled beta2-agonists, but these can be overcome without jeopardising the treatment of elite athletes with asthma.While the Code permits the use of inhaled glucocorticoids without restriction, oral and intravenous glucocorticoids are prohibited, although a mechanism exists that allows them to be administered for acute severe asthma.Although asthmatic athletes achieved outstanding sporting success during the 1950s and 1960s before any anti-doping rules existed, since introduction of the Code's policies on some drugs to manage asthma results at the Olympic Games have revealed that athletes with confirmed asthma/airway hyperresponsiveness (AHR) have outperformed their non-asthmatic rivals.It appears that years of intensive endurance training can provoke airway injury, AHR and asthma in athletes without any past history of asthma. Although further research is needed, it appears that these consequences of airway injury may abate in some athletes after they have ceased intensive training. The World Anti-Doping Code (the Code) has not prevented asthmatic individuals from becoming elite athletes. This review examines those sections of the Code that are relevant to respiratory physicians who manage elite and sub-elite athletes with asthma. The restrictions that the Code places or may place on the prescription of drugs to prevent and treat asthma in athletes are discussed. In addition, the means by which respiratory physicians are able to treat their elite asthmatic athlete patients with drugs that are prohibited in sport are outlined, along with some of the pitfalls in such management and how best to prevent or minimise them. PMID- 27408634 TI - A young man with dyspnoea and audible expiration: the loops never lie. AB - Spirometry provides clues to solving this puzzle of dyspnoea and wheeze in a young nonsmoker-the loops never lie! http://ow.ly/YC9zI A 10 s recording of expiratory sounds from this case can be found at: http://ow.ly/UVVu300moD1. PMID- 27408635 TI - The respiratory muscles during exercise. AB - Although during exercise respiratory muscles are finely controlled, they can contribute to limit performance http://ow.ly/qYUc300m9uP. PMID- 27408636 TI - LSC 2016: from system approaches in lung disease to getting the job you want. AB - Highlights of the Lung Science Conference 2016 http://ow.ly/4nsKG2. PMID- 27408638 TI - Hot Topics from the Assemblies. PMID- 27408637 TI - Targeted therapies for lung cancer: how did the game begin? AB - Landmark studies on genetic alterations underlying NSCLC have led to tailored therapies http://ow.ly/4nq0Ps. PMID- 27408639 TI - Radiology corner. PMID- 27408641 TI - Confidences de Salon: Agnes Boots. AB - Chair of the ERS Junior Members Committee, Agnes Boots, provides an insight into her life http://ow.ly/O3MX3004ktS. PMID- 27408640 TI - Assembly 8: where surgeons and pulmonologists meet. AB - Meet ERS Assembly 8: Thoracic surgery and transplantation http://ow.ly/4mIBJ3. PMID- 27408642 TI - Pulmonary rehabilitation in adults. AB - Pulmonary rehabilitation can help people with long-term lung conditions whose symptoms, such as breathlessness and being easily tired out by daily activities, seriously impact their lives. PMID- 27408643 TI - Advanced noninvasive ventilation course: the participants' view. AB - In November 2015, ERS held its first advanced noninvasive ventilation course. Here, two participants give their views of the course. PMID- 27408646 TI - Persistent hypokalaemia and abnormal chest radiography. AB - A case report of an interesting paraneoplastic syndrome http://ow.ly/YGAR3. PMID- 27408644 TI - Common causes of dyspnoea in athletes: a practical approach for diagnosis and management. AB - KEY POINTS: "Dyspnoea" during exercise is a common complaint in seemingly otherwise healthy athletes, which may be associated with fatigue and underperformance.Because dyspnoea is an general term and may be caused by numerous factors, ranging from poor aerobic fitness to serious, potentially fatal respiratory and nonrespiratory pathologies, it is important for clinicians to obtain an appropriate case history and ask relevant exercise-specific questions to fully characterise the nature of the complaint so that a targeted diagnostic plan can be developed.Exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction are two common causes of dyspnoea in athletes, and both are regularly misdiagnosed and mismanaged due to poor adherence to available practice parameters.Aside from airway dysfunction, iron deficiency and anaemia, infectious disease, and musculoskeletal conditions are common problems in athletes which ultimately may lead to complaints of dyspnoea. EDUCATIONAL AIMS: To inform readers of the common causes of dyspnoea encountered in athletes.To highlight that airway diseases, such as asthma and exercise-induced bronchoconstriction, are commonly misdiagnosed and mismanaged.To introduce readers to common nonairway causes of dyspnoea in athletes, including clinical features and general principles of diagnosis, and management.To emphasise the importance of a detailed case history and proper adherence to established protocols in evaluating and managing the dyspnoeic athlete.To provide readers with a general framework of appropriate questions that are useful for developing a targeted diagnostic plan for evaluating dyspnoeic athletes. Dyspnoea during exercise is a common chief complaint in athletes and active individuals. It is not uncommon for dyspnoeic athletes to be diagnosed with asthma, "exercise-induced asthma" or exercise induced bronchoconstriction based on their symptoms, but this strategy regularly leads to misdiagnosis and improper patient management. Dyspnoea during exercise can ultimately be caused by numerous respiratory and nonrespiratory conditions, ranging from nonpathological to potentially fatal in severity. As, such it is important for healthcare providers to be familiar with the many factors that can cause dyspnoea during exercise in seemingly otherwise-healthy individuals and have a general understanding of the clinical approach to this patient population. This article reviews common conditions that ultimately cause athletes to report dyspnoea and associated symptoms, and provides insight for developing an efficient diagnostic plan. PMID- 27408645 TI - COPD and exercise: does it make a difference? AB - KEY POINTS: Physiological changes are observed following a structured exercise training programme in patients with COPD, without changes in resting lung function.Exercise training is the cornerstone of a comprehensive pulmonary rehabilitation programme in patients with COPD.Most comorbidities in patients referred for pulmonary rehabilitation remain undiagnosed and untreated.After careful screening, it is safe for COPD patients with comorbidities to obtain significant and clinically relevant improvements in functional exercise capacity and health status after an exercise-based pulmonary rehabilitation programme. EDUCATIONAL AIMS: To inform readers of the positive effects of exercise-based pulmonary rehabilitation in patients with COPD, even with comorbid conditions.To inform readers of the importance of physical activity in patients with COPD. Exercise training is widely regarded as the cornerstone of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). Indeed, exercise training has been identified as the best available means of improving muscle function and exercise tolerance in patients with COPD. So, exercise training truly makes a difference in the life of patients with COPD. In this review, an overview is provided on the history of exercise training (as standalone intervention or as part of a comprehensive pulmonary rehabilitation programme), exercise training in comorbid patients with COPD, and the impact of physical activity counselling in a clean air environment. PMID- 27408647 TI - A persistent pneumothorax? 5-year follow-up after diagnosis of Swyer-James MacLeod syndrome. AB - Swyer-James-MacLeod syndrome should be considered in healthy patients with unilateral pulmonary hyperlucency http://ow.ly/YWps9. PMID- 27408649 TI - Zollinger-Ellison syndrome: Revelation of the gastrinoma triangle. AB - Zollinger-Ellison syndrome is a complex condition in which one or more tumors form in the patient's pancreas or upper duodenum. These tumors, called gastrinomas, secrete excessive amounts of gastrin, and almost all develop ulcers. The vast majority of gastrinomas are present within the "gastrinoma triangle," which is composed of the porta hepatis, duodenal sweep, and pancreatic head. As surgery remains the treatment of choice, localization of the primary lesion is often challenging but essential. We present a 50-year-old man with a tentative diagnosis of Zollinger-Ellison syndrome. His In-111 pentetreotide scan, fused onto a Tc-99m abdomen image, revealed an avid lesion adjacent to the duodenal loop. Operative resection was performed, and a primary pancreatic gastrinoma was diagnosed by immunohistochemical staining. The neuroendocrine tumors have somatostatin receptors upon them. Therefore, a penteteotide scan, using In-111 radiolabelled somatostatin analogues, is the current technique of choice. This dual-isotope display permits a visual perception of anatomic landmarks around the lesion. PMID- 27408650 TI - Multimodality imaging in parathyroid carcinoma: A tale of two nodules. AB - Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. Clinical indicators of carcinoma include the severity of hyperparathyroidism and presence of a palpable neck mass. Definitive diagnosis requires surgical resection and specimen histology, or documentation of metastatic disease. We present a case of parathyroid carcinoma in a young female patient with severe hyperparathyroidism, who was also found to have subclinical hyperthyroidism in the setting of an intercurrent, solitary, functioning thyroid adenoma. A diagnostic approach to parathyroid disease, combining multimodality imaging and clinicopathologic features, is discussed. PMID- 27408651 TI - Incremental value of CT in the localization of parathyroid adenomas. AB - The diagnosis of hyperparathyroidism rests on clinical and biochemical laboratory criteria. Once the diagnosis is established, it is the function of diagnostic imaging to pre-operatively find the suspected parathyroid adenoma. Traditionally, nuclear medicine techniques such as 99mTc-Sestamibi scan and ultrasound evaluation have been the mainstay in finding the neoplasm. However, results are not always satisfactory, and accurately identifying parathyroid adenomas, especially when they are multiple, remains a challenge. We report a case where careful correlation with contrast-enhanced diagnostic CT scan of the neck helped localize two parathyroid adenomas. PMID- 27408648 TI - Recent developments on the role of epigenetics in obesity and metabolic disease. AB - The increased prevalence of obesity and related comorbidities is a major public health problem. While genetic factors undoubtedly play a role in determining individual susceptibility to weight gain and obesity, the identified genetic variants only explain part of the variation. This has led to growing interest in understanding the potential role of epigenetics as a mediator of gene-environment interactions underlying the development of obesity and its associated comorbidities. Initial evidence in support of a role of epigenetics in obesity and type 2 diabetes mellitus (T2DM) was mainly provided by animal studies, which reported epigenetic changes in key metabolically important tissues following high fat feeding and epigenetic differences between lean and obese animals and by human studies which showed epigenetic changes in obesity and T2DM candidate genes in obese/diabetic individuals. More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations. These studies have also reported epigenetic differences between obese/T2DM adults and healthy controls and epigenetic changes in association with nutritional, weight loss, and exercise interventions. There is also increasing evidence from both human and animal studies that the relationship between perinatal nutritional exposures and later risk of obesity and T2DM may be mediated by epigenetic changes in the offspring. The aim of this review is to summarize the most recent developments in this rapidly moving field, with a particular focus on human EWAS and studies investigating the impact of nutritional and lifestyle factors (both pre- and postnatal) on the epigenome and their relationship to metabolic health outcomes. The difficulties in distinguishing consequence from causality in these studies and the critical role of animal models for testing causal relationships and providing insight into underlying mechanisms are also addressed. In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time. While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease. PMID- 27408652 TI - Concurrent renal-cell carcinoma and cutaneous leiomyomas: A case of HLRCC. AB - A 51-year-old Caucasian female presenting with renal-cell cancer and cutaneous leiomyomas was later diagnosed with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome. HLRCC is an autosomal dominant condition caused by a mutation in the fumarate hydratase gene, which encodes for an enzyme in the citric acid cycle. This syndrome has been reported in over 100 families throughout the world, the majority of whom are of Eastern European descent. Those with this syndrome have a significantly increased risk of developing renal-cell carcinoma, cutaneous leiomyomas, and uterine leiomyomas, and a smaller chance of developing uterine leiomyosarcomas. This syndrome has a relatively poor prognosis, with tumor metastasis occurring in approximately 50% of patients. However, more aggressive prophylactic measures and recent studies have shown potential to improve patient prognosis. PMID- 27408653 TI - Lymphoepithelioma-like carcinoma of the breast. AB - Lymphoepithelioma-like carcinoma of the breast is a rare malignancy, with fewer than 20 cases documented in the literature. Given the paucity of reported cases, there is limited information available to guide the diagnosis and management of patients with this tumor. We present a case of a 39-year-old woman with a palpable right breast mass that was initially diagnosed by core needle biopsy as infiltrating carcinoma with prominent lymphoplasmacytic stroma. Subsequent neoadjuvant chemotherapy with docetaxel, doxorubicin, and cyclophosphamide resulted in a marked decrease in the size of the mass. After wide local surgical excision, pathology revealed a lymphoepithelioma-like carcinoma of the breast. Given the excellent treatment response, our experience may help clinicians determine future therapeutic strategies for this rare breast tumor. PMID- 27408654 TI - Combined rheolytic thrombectomy and stent placement in SVC and brachiocephalic vein thrombosis due to metastatic lymphadenopathy. AB - The current management of neoplastic obstruction, SVC, and brachiocephalic vein thrombosis, especially of SVC, is based on the combined use of interventional (endovascular thrombolysis or thrombectomy, stent placement) and noninterventional (radiation, chemotherapy) means of treatment. We present the case of a forty-year-old woman with SVC and left brachiocephalic vein thrombosis secondary to lymph node metastasis of non-small-cell lung cancer. A combination of rheolytic thrombectomy (Angiojet device) and stent placement was performed for both venous sites with complete technical success. We discuss the principles of percutaneous rheolytic thrombectomy, its effectiveness, and potential complications. PMID- 27408656 TI - Key imaging characteristics for preoperative identification of cavernous sinus hemangioma. AB - Cavernous sinus hemangiomas are relatively rare but have characteristic imaging features. We present a case of a large extra-axial middle cranial fossa mass arising from the cavernous sinus in a 51-year-old female, and we describe the unique features and complications of this intracranial tumor. With the proper pre operative diagnosis, an appropriate plan can be created for these highly vascular lesions, minimizing the risks involved with surgery. PMID- 27408655 TI - Primary intramedullary melanocytoma in the cervical spinal cord: Case report and literature review. AB - A 63-year-old man with right hemiparesis was found (on MRI) to have an expansive intramedullary tumorous lesion at the C2-C3 level. After complete neurosurgical tumor resection, the tumor was histologically categorized as an intermediate grade of intramedullary melanocytoma, an uncommon neoplasm. Based on this peculiar case and review of the literature, radical surgical resection appears to be the therapy of choice for intramedullary melanocytomas. However, their high recurrence rate and aggressive behavior suggest the need for close followup with serial MRI. PMID- 27408657 TI - Right cerebellar infarction due to ipsilateral neck-rotation-induced right vertebral artery compression and occlusion, demonstrated by CT angiography. AB - Rotation-induced vertebral artery compression and occlusion with the outcome of cerebellar infarction (as opposed to the outcome of transient ischemia from hemodynamic insufficiency, known as bow hunter's stroke) is extremely rare. We report a 40-year-old male who suffered from ipsilateral neck-rotation-induced right vertebral artery compression and occlusion that resulted in right cerebellar infarction. In most reported cases, the rotation-compressed vertebral artery is located at the C1-2 level; however, our patient's compressed artery was located at the C6-7 level as demonstrated clearly by 3-dimensional CT angiography. This case report is based on a literature review and an investigation of the likely factors of this specific incident via the patient's personal details, clinical course, and diagnostic images. PMID- 27408658 TI - Isolated traumatic rupture of the gallbladder. AB - Gallbladder injury resulting from blunt abdominal trauma is rare, being found in only about 2% of patients who undergo laparotomy for abdominal trauma. Its small size and anatomic location-partially embedded in the liver tissue, surrounded by the omentum and intestines, and overlaid by the rib cage-provides good protection. Diagnosis can be difficult, and delay may result in the development of weight loss, nausea, vomiting, abdominal distension, jaundice, ascites, and abdominal pains. Delayed imaging with computed tomography can aid in diagnosis, especially in differentiating benign processes from true gallbladder injuries. Treatment for gallbladder injury is most commonly cholecystectomy. Mortality rates in patients with gallbladder injuries are related to associated injuries, including cardiac, thoracic or intra-abdominal hemorrhage, or multi-organ failure and/or brain damage. In isolated gallbladder injury, the prognosis is good. PMID- 27408659 TI - Coccidioidomycosis osteomyelitis of the knee in a 23-year-old diabetic patient. AB - Coccidioidomycosis is a pulmonary infection caused by the dimorphic fungi Coccidioides immitis and Coccidioidomycosis posadasii. This disease is endemic to the southwestern United States and has a predilection for immunocompromised patients. Diabetes mellitus has been shown to be a strong risk factor for acquiring this infection in these states. Most cases are asymptomatic or present with mild pulmonary symptoms. However, untreated pulmonary mycosis can lead to disseminated infection, most often involving meningitis, osteomyelitis, or skin and soft-tissue infections. When there is arthritis, the knee is the most common site of infection. We present a case of a 23-year-old male with longstanding, uncontrolled Type 1 diabetes mellitus who was found to have pulmonary coccidioidomycosis following diagnosis of coccidioidomycosis osteomyelitis of the knee. PMID- 27408660 TI - In utero diagnosis of caudal regression syndrome. AB - We present a case of caudal regression syndrome (CRS), a relatively uncommon defect of the lower spine accompanied by a wide range of developmental abnormalities. CRS is closely associated with pregestational diabetes and is nearly 200 times more prevalent in infants of diabetic mothers (1, 2). We report a case of prenatally suspected CRS in a fetus of a nondiabetic mother and discuss how the initial neurological abnormalities found on imaging correlate with the postnatal clinical deficits. PMID- 27408661 TI - Spontaneous ovarian hyperstimulation syndrome with primary hypothyroidism: Imaging a rare entity. AB - Ovarian hyperstimulation syndrome is a disorder associated with ovulation induction and is rarely seen in pregnant women. Very few cases of spontaneous ovarian hyperstimulation syndrome have been reported in a woman who is neither pregnant nor undergoing ovulation therapy. This case report describes how spontaneous ovarian hyperstimulation syndrome is associated with primary hypothyroidism in a 25-year-old, nonpregnant woman who is not on ovulation induction therapy. Imaging and laboratory findings confirmed the diagnosis of this rare entity, which aided the clinicians in providing prompt management and in preventing further complications. PMID- 27408662 TI - Lumbosacral lipomyelomeningocele with anomalous osseous limb in a 3-month-old female. AB - A patient with lipomyelomeningocele (known in utero) presented for MRI characterization prior to surgical procedure at three months of age. Cross sectional imaging revealed a spinal dysraphism of the lower lumbar spine, with a posterior spinal defect spanning L4 to S2 subcutaneous fat intrusion, and distal spinal cord extrusion. An osseous excrescence was also appreciated, articulating with the left iliac bone. This case demonstrates the youngest known lipomyelomeningocele with accessory limb and the abnormal growth of multiple tissue types at the site of spinal dysraphism-a potential consequence of dedifferentiated cell proliferation originating from a secondary neural tube defect or rachipagus parasitic twinning. PMID- 27408663 TI - Traumatic rupture of an intracranial dermoid cyst. AB - Intracranial dermoid cysts are congenital tumors of ectodermal origin. Rupture of these cysts can occur spontaneously, but rupture in association with trauma is reported infrequently. The diagnosis of rupture is made by the presence of lipid (cholesterol) droplets in the subarachnoid spaces and ventricles. Nonenhanced CT of the head demonstrates multiple foci of low attenuation that correspond with hyperintense signal on T1-weighted MRI. We present a case of an adult patient with rupture of an intracranial dermoid cyst, precipitated by minor trauma. PMID- 27408664 TI - 40-year-old female with menorrhagia and abdominal pain: A case of metastatic gestational trophoblastic neoplasia. AB - Choriocarcinoma is part of a rare spectrum of placental abnormalities known as gestational trophoblastic disease (GTD). It is the most invasive form of GTD, with a mortality rate approaching 100% if left untreated. It spreads predominantly hematogenously to multiple target sites, most commonly the lungs. Due to its hypervascular nature, it is often complicated by bleeding. We describe a case of choriocarcinoma in a 40-year-old female with metastases to the lungs, brain, and bilateral kidneys resulting in large retroperitoneal hematomas. PMID- 27408665 TI - Computed tomography of acute heart failure: A novel case and literature review. AB - Computed tomography (CT) is used in patients whose conditions span the gamut from healthy to critically ill. In the specific subset of patients with cardiac arrest or imminent cardiac failure who receive contrast-enhanced CT, extant literature illustrates a set of imaging findings that include inferior vena cava and hepatic parenchymal contrast reflux, pooling, and layering in a dependent fashion. We review the literature and present a case in which these findings are demonstrated along with renal venointerstitial reflux, a finding that has not been previously described. PMID- 27408666 TI - Renal arteriovenous malformation presenting with massive hematuria. AB - Renal arteriovenous malformations are abnormal communications between the intrarenal arterial and venous systems. They are a rare cause of hematuria. Color Doppler ultrasonography, multislice CT angiography, and DSA are important tools for making the diagnosis. We describe the case of a 62-year-old man with renal arteriovenous malformation who presented with gross hematuria. PMID- 27408667 TI - Postseptal Weight Placement for Paralytic Lagophthalmos. PMID- 27408668 TI - Isolated Medial Orbital Wall Blowout Fracture. PMID- 27408669 TI - Cognitive Skills and the Aging Brain: What to Expect. AB - Whether it's a special episode on the PBS series, "The Secret Life of the Brain" or an entire issue dedicated to the topic in the journal Science, a better understanding of the aging brain is viewed as a key to an improved quality of life in a world where people live longer. Despite dementia and other neurobiological disorders that are associated with aging, improved imaging has revealed that even into our seventies, our brains continue producing new neurons. Our author writes about how mental health functions react to the normal aging process, including why an aging brain may even form the basis for wisdom. PMID- 27408670 TI - Frances E. Jensen's The Teenage Brain. AB - The unpredictable and sometimes incomprehensible moods and behaviors of a teenager can be a head-scratching mystery-especially to parents. Hormones, boredom, social media, peer pressure, and drugs and alcohol are just a few of the factors to consider. Frances E. Jensen, M.D., professor and chair of neurology at the University of Pennsylvania and the mother of two sons who are now in their twenties (along with Washington Post health and science reporter and Pulitzer Prize winner Amy Ellis Nutt) look at the emerging science of the adolescent brain and provide advice based on Jensen's own research and experience as a single mother. PMID- 27408671 TI - Review: Tales from Both Sides of the Brain. AB - Our brain has two hemispheres that specialize in different jobs-the right side processes spatial and temporal information, and the left side controls speech and language. How these two sides come together to create one mind is explained by pioneering neuroscientist Michael Gazzaniga in his new book, Tales from Both Sides of the Brain : A Life in Neuroscience (Ecco/Harper Collins, 2015). Gazzaniga is director of the SAGE Center for the Study of the Mind at the University of California, Santa Barbara, and a Dana Alliance member. PMID- 27408672 TI - John Seamon's Memory & Movies: What Films Can Teach Us about Memory. AB - From trauma to amnesia to senior moments, memory has been a major plot line in films since the 1942 classic, Random Harvest. John Seamon, an author and professor of psychology whose research includes how a camera aids memory and the impact of storytelling on memory, has shifted his lens to focus on how memory has been portrayed in one of the world's most beloved art forms. PMID- 27408673 TI - Lithium to the Rescue. AB - Lithium, an element that Mother Nature has put in some drinking water sources, has been used for its curative powers for centuries. Today, it's given in capsule form as a mood stabilizer for bipolar disorder and depression. New research, however, reveals its role as a neuroprotector, and suggests that a better understanding of the role enzymes modulated by lithium play could lead to new treatments for Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other neurodegenerative disorders. PMID- 27408674 TI - The Changing Face of Recreational Drug Use. AB - Our author writes that recent data from the United Nations Office of Drugs and Crime indicate that 540 different drugs classified as new psychoactive substances (NPS) have been identified worldwide as of 2014, and this number is expected to rise. His article describes the complexity of the NPS problem, what is known about the molecular mechanisms of action, and the pharmacological effects of NPS. It also highlights some of the considerable challenges in dealing with this emerging issue. PMID- 27408675 TI - David Casarett's Stoned: A Doctor's Case for Medical Marijuana. AB - With legal cannabis sales at $5.4 billion in 2015 and expected to rise by another billion this year in the United States, legalization and marijuana's impact on health is a hot topic of national debate. Casarett, a physician at the University of Pennsylvania, immerses himself in the culture, science, and smoke of medical marijuana in order to sort out the truth behind the buzz. Our reviewer, who has authored more than 120 research papers and reviews on the regulation of synaptic inhibition and endocannabinoids, tell us what the author got right, but also overlooked on his journey to learn more about a complex and controversial subject. PMID- 27408676 TI - The Malignant Protein Puzzle. AB - When most people hear the words malignant and brain, cancer immediately comes to mind. But our authors argue that proteins can be malignant too, and can spread harmfully through the brain in neurodegenerative diseases that include Alzheimer's, Parkinson's, CTE, and ALS. Studying how proteins such as PrP, amyloid beta, tau, and others aggregate and spread, and kill brain cells, represents a crucial new frontier in neuroscience. PMID- 27408677 TI - Imaging the Neural Symphony. AB - Since the start of the new millennium, a method called two-photon microscopy has allowed scientists to peer farther into the brain than ever before. Our author, one of the pioneers in the development of this new technology, writes that "directly observing the dynamics of neural networks in an intact brain has become one of the holy grails of brain research." His article describes the advances that led to this remarkable breakthrough-one that is helping neuroscientists better understand neural networks. PMID- 27408678 TI - The Neuro Funding Rollercoaster. AB - Compared to the money dedicated to cancer and cardiology, funding for neuroscience research has lagged behind for decades. But things are starting to change. From the White House's Brain Initiative to the Ice Bucket Challenge for ALS to some recent sizeable gifts to universities, money for brain research appears to be on the rise. But, as our author explains, research and development funding from private and corporate lenders for cognitive neuroscience-an area that he has spent years tracking-is also vital to the quality of life for millions of people. PMID- 27408679 TI - A New Approach for Epilepsy. AB - About one-third of the 65 million people worldwide affected by epilepsy are treatment-resistant, and the degree to which they suffer from seizures and convulsions can vary widely. Problems occur when nerve cells in the brain fail to communicate properly. A new study has found that inhibiting an enzyme that is critical in metabolic communication has an anti-seizure effect in epileptic mice. These findings, the authors believe, may very well initiate a shift to new therapeutic approaches. PMID- 27408680 TI - High quality genome sequence and description of Enterobacter mori strain 5-4, isolated from a mixture of formation water and crude-oil. AB - Enterobacter mori strain 5-4 is a Gram-negative, motile, rod shaped, and facultatively anaerobic bacterium, which was isolated from a mixture of formation water (also known as oil-reservior water) and crude-oil in Karamay oilfield, China. To date, there is only one E. mori genome has been sequenced and very little knowledge about the mechanism of E. mori adapted to the petroleum reservoir. Here, we report the second E. mori genome sequence and annotation, together with the description of features for this organism. The 4,621,281 bp assembly genome exhibits a G + C content of 56.24% and contains 4,317 protein coding and 65 RNA genes, including 5 rRNA genes. PMID- 27408681 TI - Permanent draft genome sequence of sulfoquinovose-degrading Pseudomonas putida strain SQ1. AB - Pseudomonas putida SQ1 was isolated for its ability to utilize the plant sugar sulfoquinovose (6-deoxy-6-sulfoglucose) for growth, in order to define its SQ degradation pathway and the enzymes and genes involved. Here we describe the features of the organism, together with its draft genome sequence and annotation. The draft genome comprises 5,328,888 bp and is predicted to encode 5,824 protein coding genes; the overall G + C content is 61.58 %. The genome annotation is being used for identification of proteins that might be involved in SQ degradation by peptide fingerprinting-mass spectrometry. PMID- 27408682 TI - Long noncoding RNAs in DNA methylation: new players stepping into the old game. AB - Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level. Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation. Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs). PMID- 27408683 TI - Spinal neurenteric cyst in a dog. AB - A 2-year-old female crossbreed dog was presented with progressive ataxia and paraparesis. A T3-L3 spinal lesion was determined by neurological examination. Magnetic resonance imaging (MRI) revealed an ovoid-shaped, well-circumscribed mass affecting the spinal cord at the level of the T9 vertebra. A left hemilaminectomy and a durotomy at the level of T9 allowed discovery of an ovoid deformation of the meninges with a cystic appearance. En bloc removal was performed and appeared to be complete. Pathological analysis showed a voluminous cystic lesion lined by a heterogeneous epithelium. Three types of epithelium were present: a pseudostratified columnar epithelium, a stratified squamous epithelium and a transitional epithelium. Mucus production, the morphology of some cells with microvilli at the apical pole and immunohistochemical assays were highly in favor of an endodermal origin of the cyst. The age of the dog, anamnesis, MRI study and histological findings were consistent with an intradural neurenteric cyst as described in humans. Total surgical removal led to a progressive clinical improvement with no recurrence at 18 months. We report an unusual intradural extramedullary cyst, called a neurenteric cyst, in a 2-year-old female crossbreed dog. This type of cyst is well-known in humans but has never been described in dogs. We propose that neurenteric cysts should be included in the differential diagnoses for tumor-like or cystic intradural lesions in the young dog. Prognosis for this type of cyst seems to be good, as total surgical removal led to a progressive clinical improvement with no recurrence at 18 months. PMID- 27408685 TI - "The molecule's the thing:" the promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results. AB - Clinical genomics is now a reality and lies at the heart of individualized medicine efforts. The success of these approaches is evidenced by the increasing volume of publications that report causal links between genomic variants and disease. In spite of early success, clinical genomics currently faces significant challenges in establishing the relevance of the majority of variants identified by next generation sequencing tests. Indeed, the majority of mutations identified are harbored by proteins whose functions remain elusive. Herein we describe the current scenario in genomic testing and in particular the burden of variants of unknown significance (VUSs). We highlight a role for molecular modeling and molecular dynamic simulations as tools that can significantly increase the yield of information to aid in the evaluation of pathogenicity. Though the application of these methodologies to the interpretation of variants identified by genomic testing is not yet widespread, we predict that an increase in their use will significantly benefit the mission of clinical genomics for individualized medicine. PMID- 27408684 TI - Voltage-gated sodium channel as a target for metastatic risk reduction with re purposed drugs. AB - OBJECTIVE: To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties. MATERIAL AND METHODS: A review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it was tested with this purpose in the experimental and clinical settings. RESULTS: The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole. Each of them are independently described and analyzed. CONCLUSIONS: The above mentioned pharmaceuticals have shown anti-metastatic and anti-invasion activity and many of them deserve to be tested in well-planned clinical trials as adjunct therapies for solid tumors and as anti-metastatic agents. Antiepileptic drugs like phenytoin, carbamazepine and valproate and the vasodilator flunarizine emerged as particularly useful for anti metastatic purposes. PMID- 27408686 TI - Assessment of pharmacogenomic agreement. AB - In 2013 we published an analysis demonstrating that drug response data and gene drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. Reanalyzing the authors' published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings. PMID- 27408687 TI - Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa. AB - Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB) is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India. PMID- 27408688 TI - Case Report: Kikuchi-Fujimoto disease: a diagnostic and therapeutic dilemma following pretransplant nephrectomy for a 2.35 Kg kidney. AB - Kikuchi-Fujimoto disease (KFD) is an extremely rare disease with a worldwide distribution and higher prevalence in Asians. It is a benign and self-limiting disorder, characterized by regional cervical lymphadenopathy accompanied with mild fever and night sweats. Lymph node histopathology is diagnostic and treating physicians should be aware of this entity as it may mimic other systemic diseases like systemic lupus erythematosus, tuberculosis, malignant lymphoma, and more rarely adenocarcinoma. Key features on lymph node biopsy are fragmentation, necrosis and karyorrhexis. Treatment includes symptomatic care, analgesics antipyretics, corticosteroids and spontaneous recovery occurs in 1 to 4 months. We report a case of adult polycystic kidney disease (ADPKD) with end stage renal disease and episodes of fever and cervical lymphadenopathy. The infectious screen was negative and on extensive workup, the patient was found to have histiocytic necrotizing lymphadenitis, which clinched the diagnosis of KFD. PMID- 27408689 TI - Stroke rehabilitation research needs to be different to make a difference. AB - Stroke continues to be a major cause of adult disability. In contrast to progress in stroke prevention and acute medical management, there have been no major breakthroughs in rehabilitation therapies. Most stroke rehabilitation trials are conducted with patients at the chronic stage of recovery and this limits their translation to clinical practice. Encouragingly, several multi-centre rehabilitation trials, conducted during the first few weeks after stroke, have recently been reported; however, all were negative. There is a renewed focus on improving the quality of stroke rehabilitation research through greater harmonisation and standardisation of terminology, trial design, measures, and reporting. However, there is also a need for more pragmatic trials to test interventions in a way that assists their translation to clinical practice. Novel interventions with a strong mechanistic rationale need to be tested in both explanatory and pragmatic trials if we are to make a meaningful difference to stroke rehabilitation practice and outcomes. PMID- 27408690 TI - Recent advances in understanding transcription termination by RNA polymerase II. AB - Transcription termination is a fundamental process in which RNA polymerase ceases RNA chain extension and dissociates from the chromatin template, thereby defining the end of the transcription unit. Our understanding of the biological role and functional importance of termination by RNA polymerase II and the range of processes in which it is involved has grown significantly in recent years. A large set of nucleic acid-binding proteins and enzymes have been identified as part of the termination machinery. A greater appreciation for the coupling of termination to RNA processing and metabolism has been recognized. In addition to serving as an essential step at the end of the transcription cycle, termination is involved in the regulation of a broad range of cellular processes. More recently, a role for termination in pervasive transcription, non-coding RNA regulation, genetic stability, chromatin remodeling, the immune response, and disease has come to the fore. Interesting mechanistic questions remain, but the last several years have resulted in significant insights into termination and an increasing recognition of its biological importance. PMID- 27408691 TI - Super resolution microscopy is poised to reveal new insights into the formation and maturation of dendritic spines. AB - Dendritic spines and synapses are critical for neuronal communication, and they are perturbed in many neurological disorders; however, the study of these structures in living cells has been hindered by their small size. Super resolution microscopy, unlike conventional light microscopy, is diffraction unlimited and thus is well suited for imaging small structures, such as dendritic spines and synapses. Super resolution microscopy has already revealed important new information about spine and synapse morphology, actin remodeling, and nanodomain composition in both healthy cells and diseased states. In this review, we highlight the advancements in probes that make super resolution more amenable to live-cell imaging of spines and synapses. We also discuss recent data obtained by super resolution microscopy that has advanced our knowledge of dendritic spine and synapse structure, organization, and dynamics in both healthy and diseased contexts. Finally, we propose a series of critical questions for understanding spine and synapse formation and maturation that super resolution microscopy is poised to answer. PMID- 27408692 TI - Chemotherapy-induced peripheral neuropathy: an update on the current understanding. AB - Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. PMID- 27408693 TI - Statin-induced diabetes: incidence, mechanisms, and implications. AB - Persuasive data from many randomized controlled trials and large, long-term observational studies indicate a modestly increased risk for the emergence of new diabetes after statin initiation. Several meta-analyses of many statin trials as well as longitudinal population-based studies suggest that the risk factors for diabetes in statin-treated persons include underlying risk for diabetes at baseline (specifically features of metabolic syndrome), the intensity of statin therapy, certain genetic traits independent of diabetes risk, and adherence to lifestyle factors. Limited data suggest statins modestly worsen hyperglycemia and A1c levels in those with pre-existing diabetes or glucose intolerance. The precise mechanism(s) of diabetogenesis with statin therapy are unclear, but impaired insulin sensitivity and compromised beta cell function via enhanced intracellular cholesterol uptake due to inhibition of intracellular cholesterol synthesis by statins, as well as other mechanisms, may be involved. Furthermore, while statins are known to have anti-inflammatory effects, it is hypothesized that, under dysmetabolic conditions, they might have pro-inflammatory effects via induction of certain inflammasomes. This concept requires further elucidation in the human. Finally, it is clear that the risk-benefit ratio for cardiovascular disease events is strongly in favor of statin therapy in those at risk, despite the emergence of new diabetes. Adherence to lifestyle regimen is critical in the prevention of new diabetes on statins. PMID- 27408694 TI - Management of postpartum haemorrhage. AB - Postpartum Haemorrhage (PPH) is a major cause of maternal morbidity and mortality. Treatment of acquired coagulopathy observed in severe PPH is an important part of PPH management, but is mainly based on literature in trauma patients, and data thus should be interpreted with caution. This review describes recent advances in transfusion strategy and in the use of tranexamic acid and fibrinogen concentrates in women with PPH. PMID- 27408695 TI - The regulation of hematopoietic stem cell populations. AB - Evidence presented over the last few years indicates that the hematopoietic stem cell (HSC) compartment comprises not just one but a number of different cell populations. Based on HSCs' proliferation and engraftment potential, it has been suggested that there are two classes of HSC, with long- and short-term engraftment potential. HSC heterogeneity seems to involve differentiation capacities as well, since it has been shown that some HSC clones are able to give rise to both myeloid and lymphoid progeny, whereas others are lymphoid deficient. It has been recognized that HSC function depends on intrinsic cell regulators, which are modulated by external signals. Among the former, we can include transcription factors and non-coding RNAs as well as epigenetic modifiers. Among the latter, cytokines and extracellular matrix molecules have been implicated. Understanding the elements and mechanisms that regulate HSC populations is of significant relevance both in biological and in clinical terms, and research in this area still has to face several complex and exciting challenges. PMID- 27408696 TI - Production of Basal Bodies in bulk for dense multicilia formation. AB - Centriole number is normally under tight control and is directly linked to ciliogenesis. In cells that use centrosomes as mitotic spindle poles, one pre existing mother centriole is allowed to duplicate only one daughter centriole per cell cycle. In multiciliated cells, however, many centrioles are generated to serve as basal bodies of the cilia. Although deuterosomes were observed more than 40 years ago using electron microscopy and are believed to produce most of the basal bodies in a mother centriole-independent manner, the underlying molecular mechanisms have remained unknown until recently. From these findings arise more questions and a call for clarifications that will require multidisciplinary efforts. PMID- 27408698 TI - Mechanisms of low back pain: a guide for diagnosis and therapy. AB - Chronic low back pain (CLBP) is a chronic pain syndrome in the lower back region, lasting for at least 3 months. CLBP represents the second leading cause of disability worldwide being a major welfare and economic problem. The prevalence of CLBP in adults has increased more than 100% in the last decade and continues to increase dramatically in the aging population, affecting both men and women in all ethnic groups, with a significant impact on functional capacity and occupational activities. It can also be influenced by psychological factors, such as stress, depression and/or anxiety. Given this complexity, the diagnostic evaluation of patients with CLBP can be very challenging and requires complex clinical decision-making. Answering the question "what is the pain generator" among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a mis-diagnosis can generate therapeutical mistakes. Traditionally, the notion that the etiology of 80% to 90% of LBP cases is unknown has been mistaken perpetuated across decades. In most cases, low back pain can be attributed to specific pain generator, with its own characteristics and with different therapeutical opportunity. Here we discuss about radicular pain, facet Joint pain, sacro-iliac pain, pain related to lumbar stenosis, discogenic pain. Our article aims to offer to the clinicians a simple guidance to identify pain generators in a safer and faster way, relying a correct diagnosis and further therapeutical approach. PMID- 27408697 TI - Models of intestinal infection by Salmonella enterica: introduction of a new neonate mouse model. AB - Salmonella enterica serovar Typhimurium is a foodborne pathogen causing inflammatory disease in the intestine following diarrhea and is responsible for thousands of deaths worldwide. Many in vitro investigations using cell culture models are available, but these do not represent the real natural environment present in the intestine of infected hosts. Several in vivo animal models have been used to study the host-pathogen interaction and to unravel the immune responses and cellular processes occurring during infection. An animal model for Salmonella-induced intestinal inflammation relies on the pretreatment of mice with streptomycin. This model is of great importance but still shows limitations to investigate the host-pathogen interaction in the small intestine in vivo. Here, we review the use of mouse models for Salmonella infections and focus on a new small animal model using 1-day-old neonate mice. The neonate model enables researchers to observe infection of both the small and large intestine, thereby offering perspectives for new experimental approaches, as well as to analyze the Salmonella-enterocyte interaction in the small intestine in vivo. PMID- 27408699 TI - Recent advances in understanding ichthyosis pathogenesis. AB - The ichthyoses, also known as disorders of keratinization (DOK), encompass a heterogeneous group of skin diseases linked by the common finding of abnormal barrier function, which initiates a default compensatory pathway of hyperproliferation, resulting in the characteristic clinical manifestation of localized and/or generalized scaling. Additional cutaneous findings frequently seen in ichthyoses include generalized xerosis, erythroderma, palmoplantar keratoderma, hypohydrosis, and recurrent infections. In 2009, the Ichthyosis Consensus Conference established a classification consensus for DOK based on pathophysiology, clinical manifestations, and mode of inheritance. This nomenclature system divides DOK into two main groups: nonsyndromic forms, with clinical findings limited to the skin, and syndromic forms, with involvement of additional organ systems. Advances in next-generation sequencing technology have allowed for more rapid and cost-effective genetic analysis, leading to the identification of novel, rare mutations that cause DOK, many of which represent phenotypic expansion. This review focuses on new findings in syndromic and nonsyndromic ichthyoses, with emphasis on novel genetic discoveries that provide insight into disease pathogenesis. PMID- 27408700 TI - Thirty-five years of research into ribozymes and nucleic acid catalysis: where do we stand today? AB - Since the discovery of the first catalytic RNA in 1981, the field of ribozyme research has developed from the discovery of catalytic RNA motifs in nature and the elucidation of their structures and catalytic mechanisms, into a field of engineering and design towards application in diagnostics, molecular biology and medicine. Owing to the development of powerful protocols for selection of nucleic acid catalysts with a desired functionality from random libraries, the spectrum of nucleic acid supported reactions has greatly enlarged, and importantly, ribozymes have been accompanied by DNAzymes. Current areas of research are the engineering of allosteric ribozymes for artificial regulation of gene expression, the design of ribozymes and DNAzymes for medicinal and environmental diagnostics, and the demonstration of RNA world relevant ribozyme activities. In addition, new catalytic motifs or novel genomic locations of known motifs continue to be discovered in all branches of life by the help of high-throughput bioinformatic approaches. Understanding the biological role of the catalytic RNA motifs widely distributed in diverse genetic contexts belongs to the big challenges of future RNA research. PMID- 27408701 TI - Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. AB - Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID- 27408702 TI - Recent insights: mesenchymal stromal/stem cell therapy for acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) causes respiratory failure, which is associated with severe inflammation and lung damage and has a high mortality and for which there is no therapy. Mesenchymal stromal/stem cells (MSCs) are adult multi-progenitor cells that can modulate the immune response and enhance repair of damaged tissue and thus may provide a therapeutic option for ARDS. MSCs demonstrate efficacy in diverse in vivo models of ARDS, decreasing bacterial pneumonia and ischemia-reperfusion-induced injury while enhancing repair following ventilator-induced lung injury. MSCs reduce the pro-inflammatory response to injury while augmenting the host response to bacterial infection. MSCs appear to exert their effects via multiple mechanisms-some are cell interaction dependent whereas others are paracrine dependent resulting from both soluble secreted products and microvesicles/exosomes derived from the cells. Strategies to further enhance the efficacy of MSCs, such as by overexpressing anti-inflammatory or pro-repair molecules, are also being investigated. Encouragingly, early phase clinical trials of MSCs in patients with ARDS are under way, and experience with these cells in trials for other diseases suggests that the cells are well tolerated. Although considerable translational challenges, such as concerns regarding cell manufacture scale-up and issues regarding cell potency and batch variability, must be overcome, MSCs constitute a highly promising potential therapy for ARDS. PMID- 27408703 TI - Recent advances in molecular genetics of melanoma progression: implications for diagnosis and treatment. AB - According to the multi-step carcinogenesis model of cancer, initiation results in a benign tumor and subsequent genetic alterations lead to tumor progression and the acquisition of the hallmarks of cancer. This article will review recent discoveries in our understanding of initiation and progression in melanocytic neoplasia and the impact on diagnostic dermatopathology. PMID- 27408704 TI - Advances in genetics: widening our understanding of prostate cancer. AB - Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients. PMID- 27408706 TI - Urinary tract infection in the setting of vesicoureteral reflux. AB - Vesicoureteral reflux (VUR) is the most common underlying etiology responsible for febrile urinary tract infections (UTIs) or pyelonephritis in children. Along with the morbidity of pyelonephritis, long-term sequelae of recurrent renal infections include renal scarring, proteinuria, and hypertension. Treatment is directed toward the prevention of recurrent infection through use of continuous antibiotic prophylaxis during a period of observation for spontaneous resolution or by surgical correction. In children, bowel and bladder dysfunction (BBD) plays a significant role in the occurrence of UTI and the rate of VUR resolution. Effective treatment of BBD leads to higher rates of spontaneous resolution and decreased risk of UTI. PMID- 27408705 TI - Extracoporeal photopheresis treatment of acute graft-versus-host disease following allogeneic haematopoietic stem cell transplantation. AB - Acute graft-versus-host disease (aGvHD) continues to be a major obstacle to allogeneic haematopoietic stem cell transplantation. Thymic damage secondary to aGvHD along with corticosteroids and other non-selective T lymphocyte-suppressive agents used in the treatment of aGvHD concurrently impair thymopoiesis and negatively impact on immunoreconstitution of the adaptive immune compartment and ultimately adversely affect clinical outcome. Extracorporeal photopheresis (ECP) is an alternative therapeutic strategy that appears to act in an immunomodulatory fashion, potentially involving regulatory T lymphocytes and dendritic cells. By promoting immune tolerance and simultaneously avoiding systemic immunosuppression, ECP could reduce aGvHD and enable a reduction in other immunosuppression, allowing thymic recovery, restoration of normal T lymphopoiesis, and complete immunoreconstitution with improved clinical outcome. Although the safety and efficacy of ECP has been demonstrated, further randomised controlled studies are needed as well as elucidation of the underlying mechanisms responsible and the effect of ECP on thymic recovery. PMID- 27408707 TI - Recent Insights into Cell Surface Heparan Sulphate Proteoglycans and Cancer. AB - A small group of cell surface receptors are proteoglycans, possessing a core protein with one or more covalently attached glycosaminoglycan chains. They are virtually ubiquitous and their chains are major sites at which protein ligands of many types interact. These proteoglycans can signal and regulate important cell processes, such as adhesion, migration, proliferation, and differentiation. Since many protein ligands, such as growth factors, morphogens, and cytokines, are also implicated in tumour progression, it is increasingly apparent that cell surface proteoglycans impact tumour cell behaviour. Here, we review some recent advances, emphasising that many tumour-related functions of proteoglycans are revealed only after their modification in processes subsequent to synthesis and export to the cell surface. These include enzymes that modify heparan sulphate structure, recycling of whole or fragmented proteoglycans into exosomes that can be paracrine effectors or biomarkers, and lateral interactions between some proteoglycans and calcium channels that impact the actin cytoskeleton. PMID- 27408708 TI - Recent advances in imaging subcellular processes. AB - Cell biology came about with the ability to first visualize cells. As microscopy techniques advanced, the early microscopists became the first cell biologists to observe the inner workings and subcellular structures that control life. This ability to see organelles within a cell provided scientists with the first understanding of how cells function. The visualization of the dynamic architecture of subcellular structures now often drives questions as researchers seek to understand the intricacies of the cell. With the advent of fluorescent labeling techniques, better and new optical techniques, and more sensitive and faster cameras, a whole array of questions can now be asked. There has been an explosion of new light microscopic techniques, and the race is on to build better and more powerful imaging systems so that we can further our understanding of the spatial and temporal mechanisms controlling molecular cell biology. PMID- 27408709 TI - Dynamical systems, attractors, and neural circuits. AB - Biology is the study of dynamical systems. Yet most of us working in biology have limited pedagogical training in the theory of dynamical systems, an unfortunate historical fact that can be remedied for future generations of life scientists. In my particular field of systems neuroscience, neural circuits are rife with nonlinearities at all levels of description, rendering simple methodologies and our own intuition unreliable. Therefore, our ideas are likely to be wrong unless informed by good models. These models should be based on the mathematical theories of dynamical systems since functioning neurons are dynamic-they change their membrane potential and firing rates with time. Thus, selecting the appropriate type of dynamical system upon which to base a model is an important first step in the modeling process. This step all too easily goes awry, in part because there are many frameworks to choose from, in part because the sparsely sampled data can be consistent with a variety of dynamical processes, and in part because each modeler has a preferred modeling approach that is difficult to move away from. This brief review summarizes some of the main dynamical paradigms that can arise in neural circuits, with comments on what they can achieve computationally and what signatures might reveal their presence within empirical data. I provide examples of different dynamical systems using simple circuits of two or three cells, emphasizing that any one connectivity pattern is compatible with multiple, diverse functions. PMID- 27408710 TI - High osteoporosis risk among East Africans linked to lactase persistence genotype. AB - This ecological correlation study explores the marked differential in osteoporosis susceptibility between East and West Africans. African tsetse belt populations are lactase non-persistent (lactose intolerant) and possess none of the genetic polymorphisms carried by lactase persistent (lactose tolerant) ethnic populations. What appears paradoxical, however, is the fact that Niger Kordofanian (NK) West African ethnicities are also at minimal risk of osteoporosis. Although East Africans share a genetic affinity with NK West Africans, they display susceptibility rates of the bone disorder closer to those found in Europe. Similar to Europeans, they also carry alleles conferring the lactase persistence genetic traits. Hip fracture rates of African populations are juxtaposed with a global model to determine whether it is the unique ecology of the tsetse-infested zone or other variables that may be at work. This project uses MINITAB 17 software for regression analyses. The research data are found on AJOL (African Journals Online), PUBMED and JSTOR (Scholarly Journal Archive). Data showing the risk of osteoporosis to be 80 times higher among East Africans with higher levels of lactase persistence than lactase non-persistence West Africans are compared with global statistics. Hip fracture rates in 40 countries exhibit a high Pearson's correlation of r=0.851, with P-value=0.000 in relation to dairy consumption. Lower correlations are seen for hip fracture incidence vis a-vis lactase persistence, per capita income and animal protein consumption. Ethnic populations who lack lactase persistence single-nucleotide polymorphisms may be at low risk of developing osteoporosis. PMID- 27408712 TI - Incarcerated ovarian herniation of the canal of Nuck in a female infant: Ultrasonographic findings and review of literature. AB - INTRODUCTION: Inguinal hernia with containing the ovary presenting as a palpable groin mass is an uncommon congenital condition, and it may cause complications such as strangulation, torsion, and infertility. We present a case of ovarian herniation into inguinal canal with sonographic findings. PRESENTATION OF CASE: A 15-day-old infant girl visited our hospital with the complaints of palpable mass in the right groin. On physical examination, a palpable non-movable mass was found in the right inguinal region, and it was irreducible. During sonographic examination, a well-circumscribed solid mass containing small cysts was found. Then, oophorectomy with high inguinal ligation was performed, and the patient was doing well after surgery. DISCUSSION: The canal of Nuck is an abnormal patent pouch of the parietal peritoneum extending to the round ligament of the uterus into the labia majora through the inguinal ring. When this canal obliterates incompletely, inguinal herniation of ovary or hydrocele occur in the female children. In the clinical practice, ovarian herniation should be differentiated from a hernia containing intestine, fat, fluid, or lymph nodes. Therefore, a careful sonographic evaluation is mandatory to make an accurate diagnosis in female infants with palpable inguinal mass. CONCLUSION: Ultrasound (US) with color Doppler US can be helpful to the diagnosis of ovarian herniation through the canal of Nuck and hernia-related complications. PMID- 27408711 TI - Models of ex vivo explant cultures: applications in bone research. AB - Ex vivo explant culture models are powerful tools in bone research. They allow investigation of bone and cartilage responses to specific stimuli in a controlled manner that closely mimics the in vivo processes. Because of limitations in obtaining healthy human bone samples the explant growth of animal tissue serves as a platform to study the complex physico-chemical properties of the bone. Moreover, these models enable preserving important cell-cell and cell-matrix interactions in order to better understand the behaviour of cells in their natural three-dimensional environment. Thus, the use of bone ex vivo explant cultures can frequently be of more physiological relevance than the use of two dimensional primary cells grown in vitro. Here, we describe isolation and ex vivo growth of different animal bone explant models including metatarsals, femoral heads, calvaria, mandibular slices and trabecular cores. We also describe how these explants are utilised to study bone development, cartilage and bone metabolism, cancer-induced bone diseases, stem cell-driven bone repair and mechanoadaptation. These techniques can be directly used to understand mechanisms linked with bone physiology or bone-associated diseases. PMID- 27408713 TI - The surgical management of male breast cancer: Time for an easy access national reporting database? AB - INTRODUCTION: Male breast cancer is extremely rare with an incidence of less than 1% of all breast cancers. Literature reports a peak of incidence at roughly 71 years of age. Management currently follows the same clinical pathways as female breast cancer as a general rule. METHODS: A retrospective search for all patients who were referred and diagnosed with male breast cancer at our centre was undertaken. Patients notes were then explored for demographics, histological staging, multidisciplinary team meeting outcome and treatment. A literature search including the search terms 'Male Breast Cancer AND Surgery' or 'Male Breast Cancer AND Experience' were used. Non English language articles, or those without abstracts were excluded. RESULTS: Seven patients were reviewed over 3 years (2006-2009). Mean agea was 69 years and mean lesion size was 15 mm. Histology was invasive ductal carcinoma for all patients. All patients were ER receptor positive. Two patients were HER2 positive. Five patients were offered mastectomy. One patient refused treatment. In follow up at 36 months there were 3 recurrences. 1 patient was lost to follow up. There were 3 mortalities. The literature search identified 72 articles. Articles were subdivided into those that discussed the surgical management of male breast cancer (n = 8), articles that discussed male breast cancer as podium presentations or posters with no full text article publication (n = 13) and finally full text publications of case experience of male breast cancer (n = 21). DISCUSSION: We report a series of seven cases of male breast cancer encountered over three years, evaluating patient demographics as well as treatment and outcomes. In our series patients were managed with mastectomy. New evidence is questioning the role of mastectomy against breast conserving surgery in male patients. Furthermore there is a lack of reporting infrastructure for national data capture of the benefits of surgical modalities. Literature review highlights the varied clinical experience between units that remains reported as podium presentation but not published. The establishment of an online international reporting registry would allow for efficient analysis of surgical outcomes to improve patient care from smaller single centres. This would facilitate large scale meta analysis by larger academic surgical centres. PMID- 27408714 TI - Perineal Paget's disease: A rare disorder and review of literature. AB - INTRODUCTION: Extramammary Paget's disease (EMPD) occurs commonly in perineum, vulva and perineal region and is considered as a complex disorder due to different clinical and histological features. PRESENTATION OF CASE: A 61 years old woman had a dermatologic evaluation for anal itch and underwent a skin biopsy with diagnostic of Paget disease in perianal region. Pelvic magnetic resonance showed a huge tumor which involved skin, derma and gluteus and she firstly refused any surgical treatment. One year later, because of increasing of the tumor and bleeding, she underwent the surgical procedure with a complete excision, resection of the skin of the anus, inguinal lymphadenectomy and left colostomy. Because of lymph nodes metastasis, a VLS Miles was sequentially performed. She started oncological follow up that showed liver, lung and pelvic metastasis. She survived for 24 months after surgery. DISCUSSION: In literature, less than 200 cases of perineal Paget's disease have been reported. EMPD in some cases has an associated adenocarcinoma, which has been associated with a worse prognosis and high mortality. Wrong diagnosis and a superficial consideration of a benign evolution should be considered as the first mistake in clinical practice. CONCLUSION: Our surgical approach is considered in literature as the best one for those cases, followed by the oncological treatment. Those patients need to be better studied and more attention should be paid to the clinical presentation. PMID- 27408715 TI - The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. AB - AIM: To investigate the effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. MATERIAL AND METHODS: This controlled, randomized, prospective cohort was carried out on 40 patients who admitted for surgery due to hyperthyroidism. Cases were randomly assigned to receive either preoperative treatment with Lugol solution (Group 1) or no preoperative treatment with Lugol solution (Group 2). Group 3 (n = 10) consisted of healthy adults with no known history and signs of hyperthyroidism. Blood flow through the thyroid arteries of patients was measured by color flow Doppler ultrasonography. Free T3, free T4, TSH, thyroid volume and the resistance index of the four main thyroid arteries were measured in all patients. RESULTS: There was not a significant difference between gender, preoperative serum thyroid hormone levels, or thyroid gland volumes between groups 1 and 2. The mean blood flow of the patients in Group 1 was significantly lower than values in Group 2. When age, gender, thyroid hormone, TSH, thyroid volume, blood flow, and Lugol solution treatment were included as independent variables, Lugol solution treatment (OR, 7.40; 95% CI, 1.02-58.46; p = 0.001) was found to be the only significant independent determinant of intraoperative blood loss. Lugol solution treatment resulted in a 7.40-fold decrease in the rate of intraoperative blood loss. CONCLUSION: Preoperative Lugol solution treatment was found to be a significant independent determinant of intraoperative blood loss. Moreover, preoperative Lugol solution treatment decreased the rate of blood flow, and intraoperative blood loss during thyroidectomy. PMID- 27408718 TI - Improving asthma severity and control screening in a primary care pediatric practice. AB - Asthma is the most commonly encountered chronic disease in children. Periodic assessment of asthma severity and control is an integral part of asthma management, but patients with uncontrolled asthma don't always schedule routine asthma care visits. The aim of this project was to improve asthma control and severity screening in a primary care setting by using a validated tool for all visits for patients with a diagnosis of asthma aged 4-21 years. Our QI team developed a protocol to administer the Asthma Control Test (TM), a validated questionnaire to assess asthma control. The stakeholders involved were the physicians, nursing staff, and the Health Information Team (HIT). All patients who had a prior diagnosis of asthma or with an asthma medication in their chart, who presented for any clinical visit including asthma were administered ACT. The staff scored the ACT and included the form in the encounter sheet so that the physicians can review the scores, address the asthma control, severity, and document in the chart. The number of patients whose asthma control was assessed improved from 10% per year to 85% after the three PDSA cycles. Administration of the tool did not impact the flow of the patients in a busy primary care practice. Screening asthma severity and control for patients diagnosed with asthma with a validated questionnaire when presenting for any chief complaint including asthma will help the provider address the severity and control of asthma symptoms in a timely manner and would potentially help prevent unwanted emergency department or urgent care usage. PMID- 27408716 TI - Efficient production of pronuclear embryos in breeding and nonbreeding season for generating transgenic sheep overexpressing TLR4. AB - BACKGROUND: Brucella is a zoonotic Gram-negative pathogen that causes abortion and infertility in ruminants and humans. TLR4 is the receptor for LPS which can recognize Brucella and initiate antigen-presenting cell activities that affect both innate and adaptive immunity. Consequently, transgenic sheep over-expressing TLR4 are an suitable model to investigate the effects of TLR4 on preventing Brucellosis. In this study, we generated transgenic sheep overexpressing TLR4 and aimed to evaluate the effects of different seasons (breeding and non-breeding season) on superovulation and the imported exogenous gene on growth. RESULTS: In total of 43 donor ewes and 166 recipient ewes in breeding season, 37 donor ewes and 144 recipient ewes in non-breeding season were selected for super-ovulation and injected embryo transfer to generate transgenic sheep. Our results indicated the no. of embryos recovered of donors and the rate of pronuclear embryos did not show any significant difference between breeding and non-breeding seasons (P > 0.05). The positive rate of exogenous TLR4 tested were 21.21 % and 22.58 % in breeding and non-breeding season by Southern blot. The expression level of TLR4 in the transgenic sheep was 1.5 times higher than in the non-transgenic group (P < 0.05). The lambs overexpressing TLR4 had similar growth performance with non transgenic lambs, and the blood physiological parameters of transgenic and non transgenic were both in the normal range and did not show any difference. CONCLUSIONS: Here we establish an efficient platform for the production of transgenic sheep by the microinjection of pronuclear embryos during the whole year. The over-expression of TLR4 had no adverse effect on the growth of the sheep. PMID- 27408717 TI - Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function. AB - Obesity is currently one of the major epidemics of this millennium and affects individuals throughout the world. It causes multiple systemic complications, some of which result in severe impairment of organs and tissues. These complications involve mechanical changes caused by the accumulation of adipose tissue and the numerous cytokines produced by adipocytes. Obesity also significantly interferes with respiratory function by decreasing lung volume, particularly the expiratory reserve volume and functional residual capacity. Because of the ineffectiveness of the respiratory muscles, strength and resistance may be reduced. All these factors lead to inspiratory overload, which increases respiratory effort, oxygen consumption, and respiratory energy expenditure. It is noteworthy that patterns of body fat distribution significantly influence the function of the respiratory system, likely via the direct mechanical effect of fat accumulation in the chest and abdominal regions. Weight loss caused by various types of treatment, including low-calorie diet, intragastric balloon, and bariatric surgery, significantly improves lung function and metabolic syndrome and reduces body mass index. Despite advances in the knowledge of pulmonary and systemic complications associated with obesity, longitudinal randomized studies are needed to assess the impact of weight loss on metabolic syndrome and lung function. PMID- 27408720 TI - Withholding treatment and intellectual disability: Second survey on end-of-life decisions in Switzerland. AB - BACKGROUND: As people live longer, they are more likely to die over a prolonged period from incurable, chronic illnesses that occur more frequently in old age. Therefore, people will experience an increase in end-of-life discussions and decisions. AIM: The aim of this study was to explore the prevalence and nature of end-of-life decisions for people with disabilities in Swiss residential homes. DESIGN: A cross-sectional survey in the three biggest German-speaking regions in Switzerland (N = 209) was conducted. SETTING: All of the residential homes for adults with disabilities (N = 209) were invited to participate in a cross sectional survey. The response quote was 76.7%. Directors provided information on 82 deaths. Chi-square and t-tests were used to study differences in prevalence and nature of end-of-life decisions between people with intellectual disability (ID) and people with other disabilities. RESULTS: An end-of-life decision was taken in 53.7% of the cases (n = 44). For people with ID, the decision to withhold treatment had been taken more often (28.9%, 13 cases) than for people with other disabilities (8.1%, 3 cases) (chi(2) (1, N = 82) = 5.58, p = 0.017). CONCLUSION: The study provides insight in end-of-life decision-making for people with disabilities in Switzerland. The results have implications on surrogate decision-making for people with ID living in residential homes. As the study partly confirms the results of previous studies, further studies will be necessary. PMID- 27408721 TI - The European Heart Rhythm Association: On the Move Towards the Future of Electrophysiology. PMID- 27408719 TI - Epidemiology of eating disorders, eating disordered behaviour, and body image disturbance in males: a narrative review. AB - Challenges to epidemiological studies of eating and related body image disturbance disorders in males include, in addition to low base rates and the predominance of residual diagnostic categories, the female-centric nature of current classification schemes and the consequent lack of appropriate assessment instruments. In this narrative review, we summarise epidemiological data regarding the prevalence and correlates of eating disorders, related body image disturbance disorders, and eating disorder features in males. Attention is focused on disorders most likely to be observed among males, such as muscle dysmorphia and muscularity-oriented excessive exercise. It is argued that, given the multiple challenges involved in research of this kind, a focus on features is more likely to advance the field than a focus on diagnoses. In terms of correlates, we focus on impairment and help-seeking, since these issues are most relevant in informing public health burden, service provision, and related issues. We end with some thoughts about current gaps in the knowledge base and directions for future research that we consider to be most promising. PMID- 27408723 TI - The dual role of rivers in facilitating or hindering movements of the false heath fritillary butterfly. AB - BACKGROUND: Species movement responses to landscape structures have been studied using a variety of methods, but movement research is still in need of simple methods that help predicting and comparing movements across structurally different landscapes. We demonstrate how habitat-specific movement models can be used to disentangle causes of differentiated movement patterns in structurally different landscapes and to predict movement patterns in altered and artificial landscapes. In our case study, we studied the role of riparian landscapes to the persistence of the endangered false heath fritillary butterfly (Melitaea diamina) in its newly discovered coastal distribution region in Finland. We compared the movement parameters of the riparian population to two reference populations by using capture-recapture data and habitat-specific diffusion modelling, and analysed the role of the river and riverbank buffer zones in facilitating or hindering false heath fritillary movement with movement simulations. RESULTS: The riparian population of the false heath fritillary did not show major differences to reference populations in terms of movement parameters within breeding habitat, high-quality matrix and low-quality matrix. However, movement simulations showed that the habitat-specific movement parameters estimated for the false heath fritillary can lead into markedly different movement patterns in structurally different landscapes. An artificial riparian landscape mimicking those of the coastal distribution resulted into more directional, longitudinal movements both parallel and perpendicular to the river than a more mosaic-like landscape, but the existence of the river in the landscape reduced movements across the river. CONCLUSIONS: Our study demonstrates how habitat-specific movement models enable comparisons of movement patterns across structurally different real, altered and artificial landscapes. As such, they can be used to compare movement parameters across populations, to study the effects of management interventions to endangered species and to identify areas that have high sensitivity to individual movement. In our case study, the river is shown to perform a dual role for the movements of the riparian false heath fritillary population. Whereas the river acts as a moderate movement barrier for the false heath fritillary, the longitudinal configuration of riverbank habitats provides a means especially for the male false heath fritillaries to move across the landscape. PMID- 27408722 TI - Pharmacological Therapy of Tachyarrhythmias During Pregnancy. AB - Tachyarrhythmias are the most frequently observed cardiac complications during pregnancy. The majority of these maternal and foetal arrhythmias are supraventricular tachyarrhythmias; ventricular tachyarrhythmias are rare. The use of anti-arrhythmic drugs (AADs) during pregnancy is challenging due to potential foetal teratogenic effects. Maintaining stable and effective therapeutic maternal drug levels is difficult due to haemodynamic and metabolic alterations. Pharmacological treatment of tachyarrhythmias is indicated in case of maternal haemodynamic instability or hydrops fetalis. Evidenc e regarding the efficacy and safety of AAD therapy during pregnancy is scarce and the choice of AAD should be based on individual risk assessments for both mother and foetus. This review outlines the current knowledge on the development of tachyarrhythmias during pregnancy, the indications for and considerations of pharmacological treatment and its potential side-effects. PMID- 27408724 TI - Patch-use dynamics by a large herbivore. AB - BACKGROUND: An adaption of the optimal foraging theory suggests that herbivores deplete, depart, and finally return to foraging patches leaving time for regrowth [van Moorter et al., Oikos 118:641-652, 2009]. Inter-patch movement and memory of patches then produce a periodic pattern of use that may define the bounds of a home range. The objective of this work was to evaluate the underlying movements within home ranges of elk (Cervus elaphus) according to the predictions of this theory. Using a spatial temporal permutation scan statistic to identify foraging patches from GPS relocations of cow elk, we evaluated return patterns to foraging patches during the 2012 growing season. Subsequently, we used negative binomial regression to assess environmental characteristics that affect the frequency of returns, and thereby characterize the most successful patches. RESULTS: We found that elk return to known patches regularly over a season, on average after 15.4 (+/-5.4 SD) days. Patches in less-rugged terrain, farther from roads and with high productivity were returned to most often when controlling for the time each patch was known to each elk. CONCLUSIONS: Instead of diffusion processes often used to describe animal movement, our research demonstrates that elk make directed return movements to valuable foraging sites and, as support for Van Moorter et al.'s [Oikos 118:641-652, 2009] model, we submit that these movements could be an integral part of home-range development in wild ungulates. PMID- 27408725 TI - Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC. AB - Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC. PMID- 27408726 TI - Prognostic factors associated with mortality of drug-resistant Acinetobacter baumannii ventilator-associated pneumonia. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) caused by drug-resistant Acinetobacter baumannii is associated with high mortality in critically ill patients. We identified the prognostic factors of 30-day mortality in patients with VAP caused by drug-resistant A. baumannii and compared survival outcomes among multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug resistant (PDR) A. baumannii VAP. METHODS: A retrospective cohort study was conducted in the Medical Intensive Care Unit at Chiang Mai University Hospital, Thailand. All adult patients diagnosed with A. baumannii VAP between 2005 and 2011 were eligible. Univariable and multivariable Cox's proportional hazards regression were performed to identify the prognostic factors of 30-day mortality. RESULTS: A total of 337 patients with microbiologically confirmed A. baumannii VAP were included. The proportion of drug-sensitive (DS), MDR, XDR, and PDR A. baumannii were 9.8%, 21.4%, 65.3%, and 3.6%, respectively. The 30-day mortality rates were 21.2%, 31.9%, 56.8%, and 66.7%, respectively. The independent prognostic factors were SOFA score >5 (hazard ratio (HR) = 3.33, 95% confidence interval (CI) 1.94-5.72, P < 0.001), presence of septic shock (HR = 2.66, 95% CI 1.71-4.12, P < 0.001), Simplified Acute Physiology Score (SAPS) II >45 (HR = 1.58, 95% CI 1.01-2.46, P = 0.045), and inappropriate initial antibiotic treatment (HR = 1.53, 95% CI 1.08-2.20, P = 0.016). CONCLUSIONS: Drug-resistant A. baumannii, particularly XDR and PDR, was associated with a high mortality rate. Septic shock, high SAPS II, high SOFA score, and inappropriate initial antibiotic treatment were independent prognostic factors for 30-day mortality. PMID- 27408727 TI - How unclogging a sink can be lethal: case report of an accidental methyl bromide poisoning leading to a multiple organ failure. AB - Methyl bromide (CH3Br) is a colorless and odorless volatile gas, used as an insecticide, fire extinguisher, fumigant, and refrigerant. Although forbidden since 1987 for domestic use, it is still used in industry, for example, to fumigate agricultural fields which are for importation in the United States. Here is the case of a 74-year-old man who was accidentally exposed to methyl bromide after using an old fire extinguisher. Even though he finally survived, he developed a severe multiple organ failure and spent 2 months in intensive care unit. We present in this report all the difficulties we had to diagnose this unusual poisoning. PMID- 27408728 TI - Extracorporeal membrane oxygenation for acute respiratory distress syndrome. AB - Extracorporeal membrane oxygenation (ECMO) can be a lifesaving therapy in patients with refractory severe respiratory failure or cardiac failure. Severe acute respiratory distress syndrome (ARDS) still has a high-mortality rate, but ECMO may be able to improve the outcome. Use of ECMO for respiratory failure has been increasing since 2009. Initiation of ECMO for adult ARDS should be considered when conventional therapy cannot maintain adequate oxygenation. ECMO can stabilize gas exchange and haemodynamic compromise, consequently preventing further hypoxic organ damage. ECMO is not a treatment for the underlying cause of ARDS. Because ARDS has multiple causes, the diagnosis should be investigated and treatment should be commenced during ECMO. Since ECMO is a complicated and high risk therapy, adequate training in its performance and creation of a referring hospital network are essential. ECMO transport may be an effective method of transferring patients with severe ARDS. PMID- 27408729 TI - The role of spontaneous effort during mechanical ventilation: normal lung versus injured lung. AB - The role of preserving spontaneous effort during mechanical ventilation and its interaction with mechanical ventilation have been actively investigated for several decades. Inspiratory muscle activities can lower the pleural components surrounding the lung, leading to an increase in transpulmonary pressure when spontaneous breathing effort is preserved during mechanical ventilation. Thus, increased transpulmonary pressure provides various benefits for gas exchange, ventilation pattern, and lung aeration. However, it is important to note that these beneficial effects of preserved spontaneous effort have been demonstrated only when spontaneous effort is modest and lung injury is less severe. Recent studies have revealed the 'dark side' of spontaneous effort during mechanical ventilation, especially in severe lung injury. The 'dark side' refers to uncontrollable transpulmonary pressure due to combined high inspiratory pressure with excessive spontaneous effort and the injurious lung inflation pattern of Pendelluft (i.e., the translocation of air from nondependent lung regions to dependent lung regions). Thus, during the early stages of severe ARDS, the strict control of transpulmonary pressure and prevention of Pendelluft should be achieved with the short-term use of muscle paralysis. When there is preserved spontaneous effort in ARDS, spontaneous effort should be maintained at a modest level, as the transpulmonary pressure and the effect size of Pendelluft depend on the intensity of the spontaneous effort. PMID- 27408731 TI - Transport choice when travelling to a sports facility: the role of perceived route features - Results from a cross-sectional study in the Netherlands. AB - BACKGROUND: Physical activity and sedentary behaviour are independently associated with health outcomes, where physical activity (PA) is associated with health benefits and sedentary behaviour is associated with health risks. One possible strategy to counteract sedentary behaviour is to stimulate active transport use. As monitoring studies in the Netherlands have shown that among sedentary people the proportion of adults who engage in sports (hereafter: sports practitioners) is 62.3%, sports practitioners seem a feasible target group for this strategy. Previous studies have generally reported associations between neighbourhood characteristics and active transport use. However, the neighbourhood covers only part of the route to a certain destination. Therefore, we examined the association between perceived route features and transport choice when travelling up to 7.5 kilometres to a sports facility among sports practitioners. METHODS: For 1118 Dutch sports practitioners - who indicated that they practice a sport and travel to a sports facility - age 18 and older, data on transport choice and perceived features of the route to a sports facility were gathered. Participants were classified into one of three transport groups based on their transport choice: car users, cyclists and walkers. Participants were asked whether perceived route features influenced their transport choice. Logistic regression was used to model the odds of cycling versus car use and walking versus car use in the association with perceived route features, adjusted for potential confounders. RESULTS: Perceived traffic safety was associated with lower odds of cycling (OR: 0.36, 95% CI: 0.15-0.86). Perceived route duration was associated with lower odds of both cycling (OR: 0.54, 95%CI: 0.39-0.75) and walking (OR: 0.60, 95%CI: 0.36-1.00). Perceived distance to a sports facility and having to make a detour when using other transport modes than the chosen transport mode were associated with higher odds of both cycling and walking (ORrange: 1.82-5.21). What and who people encountered during their trip (i.e. visual aspects) was associated with higher odds of both cycling and walking (ORrange: 2.40-3.69). CONCLUSIONS: Perceived traffic safety, duration, distance, detour, and visual aspects, when travelling to a sports facility were associated with transport choice. Therefore, the perception of route features should be considered when stimulating active transport use among sports practitioners. PMID- 27408732 TI - "Actinomyces ihumii," a new bacterial species isolated from the digestive microbiota of a HIV-infected patient. AB - We report the main properties of "Actinomyces ihumii" strain SD1 (= CSUR P2006) isolated from the stool of a 50-year-old HIV-infected man. PMID- 27408730 TI - Biomechanical symmetry in elite rugby union players during dynamic tasks: an investigation using discrete and continuous data analysis techniques. AB - BACKGROUND: While measures of asymmetry may provide a means of identifying individuals predisposed to injury, normative asymmetry values for challenging sport specific movements in elite athletes are currently lacking in the literature. In addition, previous studies have typically investigated symmetry using discrete point analyses alone. This study examined biomechanical symmetry in elite rugby union players using both discrete point and continuous data analysis techniques. METHODS: Twenty elite injury free international rugby union players (mean +/- SD: age 20.4 +/- 1.0 years; height 1.86 +/- 0.08 m; mass 98.4 +/- 9.9 kg) underwent biomechanical assessment. A single leg drop landing, a single leg hurdle hop, and a running cut were analysed. Peak joint angles and moments were examined in the discrete point analysis while analysis of characterising phases (ACP) techniques were used to examine the continuous data. Dominant side was compared to non-dominant side using dependent t-tests for normally distributed data or Wilcoxon signed-rank test for non-normally distributed data. The significance level was set at alpha = 0.05. RESULTS: The majority of variables were found to be symmetrical with a total of 57/60 variables displaying symmetry in the discrete point analysis and 55/60 in the ACP. The five variables that were found to be asymmetrical were hip abductor moment in the drop landing (p = 0.02), pelvis lift/drop in the drop landing (p = 0.04) and hurdle hop (p = 0.02), ankle internal rotation moment in the cut (p = 0.04) and ankle dorsiflexion angle also in the cut (p = 0.01). The ACP identified two additional asymmetries not identified in the discrete point analysis. CONCLUSIONS: Elite injury free rugby union players tended to exhibit bi-lateral symmetry across a range of biomechanical variables in a drop landing, hurdle hop and cut. This study provides useful normative values for inter-limb symmetry in these movement tests. When examining symmetry it is recommended to incorporate continuous data analysis techniques rather than a discrete point analysis alone; a discrete point analysis was unable to detect two of the five asymmetries identified. PMID- 27408734 TI - Haloferax massiliensis sp. nov., the first human-associated halophilic archaea. AB - We report the main characteristics of Haloferax massiliensis strain Arc-Hr(T) (= CSUR P974) isolated from stool specimen of a 22-year-old Amazonian obese female patient. PMID- 27408733 TI - "Emergencia timonensis," a new bacterium isolated from the stool of a healthy patient. AB - We present the essential characteristics of "Emergencia timonensis" strain SN18 (= CSUR P2260), a new member of the order Clostridiales that was isolated from the stool of healthy patient. PMID- 27408735 TI - "Africanella massiliensis," a new bacterial genus isolated from human gut microbiota. AB - We report the main characteristics of "Africanella massiliensis" strain Marseille P2538 (= CSUR P2538), isolated from the gut microbiota of a healthy 44-month-old girl from Niger. PMID- 27408736 TI - 'Peptoniphilus raoultii' sp. nov., a new species isolated from human female genital tract. AB - We report the principal characteristics of 'Peptoniphilus raoultii' strain KHD4 (= CSUR P0110), a new member of the Peptoniphilus genus. Strain KHD4 was isolated from the vaginal flora of a 33-year-old woman with bacterial vaginosis. PMID- 27408737 TI - Christensenella timonensis, a new bacterial species isolated from the human gut. AB - We propose a new species, Christensenella timonensis, strain Marseille-P2437(T) (CSUR P2437(T)), which was isolated from gut microbiota of a 66-year-old patient as a part of culturomics study. C. timonensis represents the second species isolated within the Christensenella genus. PMID- 27408738 TI - Butyricimonas virosa bacteraemia and bowel disease: case report and review. AB - Only two cases of human infection with the anaerobic Gram-negative bacillus Butyricimonas virosa have been previously reported. We describe the case of a 69 year-old man with B. virosa and diverticulitis, further supporting an association of bacteraemia with this pathogen to bowel disease. We also summarize the characteristics of the previously described cases. PMID- 27408739 TI - 'Peptoniphilus pacaensis' sp. nov., a new species isolated from human female genital tract. AB - We relate here the primary characteristics of 'Peptoniphilus pacaensis' strain KHD5 (= CSUR P2271), a new member of the Peptoniphilus genus. Strain KHD5 was isolated from a vaginal sample of a 33-year-old woman exhibiting a bacterial vaginosis. PMID- 27408740 TI - Mitral endocarditis due to Rothia aeria with cerebral haemorrhage and femoral mycotic aneurysms, first French description. AB - Rothia aeria is a Rothia species from the Micrococcaceae family. We report here the first French R. aeria endocarditis complicated by brain haemorrhage and femoral mycotic aneurysms. Altogether, severity and antimicrobial susceptibility should make us consider the management of R. aeria endocarditis as Staphylococcus aureus methicillin-susceptible endocarditis. PMID- 27408741 TI - 'Negativicoccus massiliensis', a new species identified from human stool from an obese patient after bariatric surgery. AB - We report here the main characteristics of 'Negativicoccus massiliensis' strain AT7 (CSURP = P2082, DSM = 100853) isolated from a stool sample collected from a 47-year-old obese French man before bariatric surgery. PMID- 27408742 TI - 'Marseilla massiliensis' gen. nov., sp. nov., isolated from human right colon. AB - We report here the main characteristics of 'Marseilla massiliensis' strain Marseille-P2475(T) (CSURP2475) isolated from the human right colon. PMID- 27408743 TI - 'Bacteroides mediterraneensis' sp. nov., a new human-associated bacterium isolated from ileum specimen. AB - We report here the main characteristics of 'Bacteroides mediterraneensis' strain Marseille-P2644(T) (CSURP2644) that was isolated from the stored samples of gut. PMID- 27408744 TI - Infective endocarditis caused by Streptococcus tigurinus-like organisms. AB - Streptococcus species are important causes of infective endocarditis but species identification remains challenging. We report two cases of infective endocarditis due to Streptococcus tigurinus-like organisms, which were first identified by 16S ribosomal RNA gene sequence analysis and subsequently confirmed using phylogeny based on the analysis of the shetA gene encoding exfoliative toxin. PMID- 27408745 TI - 'Mediterranea massiliensis' gen. nov., sp. nov., a new human-associated bacterium isolated from the right and left colon lavage of a 58-year-old patient. AB - We report here the main characteristics of 'Mediterranea massiliensis' strain Marseille-P2645(T) (CSURP2645) that was isolated from stored samples of gut. PMID- 27408746 TI - Anaerococcus urinomassiliensis sp. nov., isolated from a urine sample of a 17 year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis. AB - We report the main characteristics of 'Anaerococcus urinomassiliensis' strain FC4(T) (CSURP2143) that was isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis. PMID- 27408747 TI - Corrigendum to "First detection of Aspergillus fumigatus azole resistant strain due to Cyp51A TR46/Y121F/T289A in an azole-naive patient in Spain" [New Microbes New Infect 6 (2015) 33-34]. AB - [This corrects the article DOI: 10.1016/j.nmni.2015.04.005.]. PMID- 27408748 TI - On-line micro column preconcentration system based on amino bimodal mesoporous silica nanoparticles as a novel adsorbent for removal and speciation of chromium (III, VI) in environmental samples. AB - BACKGROUND: Chromium (VI) has toxic and carcinogenic effects. So, determination and speciation of chromium in environmental samples is very important in view of health hazards. In this study, solid phase extraction (SPE) based on bulky amine functionalized bimodal mesoporous silica nanoparticles (NH2-UVM-7) as a novel nanoadsorbent was applied for preconcentration and speciation of chromium (III, VI) in water samples. METHODS: UVM-7 was synthesized via atrane route and subsequently functionalized with amino silane via grafting method. In SPE procedure, polymer tubing as a micro-column was filled with NH2-UVM-7 adsorbent. Preconcentration and speciation of Cr (III) and Cr (VI) ions with NH2-UVM-7 were obtained in water samples due to the fact that only Cr (VI) ions can be complexed with-NH2 groups at optimized pH. Finally, chromium concentration was determined by flame atomic absorption spectrometry (F-AAS). RESULTS: TEM, XRD, and SEM results confirmed the beneficial properties of NH2-UVM-7 as the adsorbent for chromium extraction. Under the optimal conditions, linear calibration curve, detection limit and preconcentration factor were obtained 6-320 MUg/ L, 1.2 MUg/L and 66.7, respectively (RSD < 5 %). The efficiency of nanoadsorbent for preconcentration and extraction of Cr (VI) was 96 %, whereas it was less than 5 % for Cr (III). CONCLUSIONS: The developed NH2-UVM7-based SPE/F-AAS method has enough sensitively and simplicity for speciation and determination of Cr (VI) and Cr (III) ions in real water samples. Good recoveries, with low detection limits and good preconcentration factors are the main advantages of this procedure. PMID- 27408749 TI - Long term follow-up of a phase II trial of multimodal therapy given in a "sandwich" method for stage III, IV, and recurrent endometrial cancer. AB - BACKGROUND: Our objective was to determine if previously reported overall survival (OS) and progression-free survival (PFS) rates are maintained long term following multimodal therapy for advanced and recurrent endometrial cancer and to assess the lymphedema rates associated with this therapy. METHODS: Women with advanced-stage or recurrent endometrial cancer were recruited between 9/2004 and 6/2009 to our previously published Phase II trial. Patients received intravenous docetaxel (75 mg/m2) and carboplatin (AUC = 6) every 3 weeks for 3 cycles before and after radiation therapy. Patient outcomes were updated in July 2014. Data abstracted included presence of lymphedema, disease progression, and death. OS and PFS estimates at 5 years were calculated using Kaplan-Meier methods. RESULTS: Of the 41 patients enrolled, 10 (24 %) had stage IIIA and 21 (51 %) had stage IIIC disease; 32 (78 %) had endometrioid histology; and 35 (85 %) completed the protocol. With a median follow-up of 5 years, 15 of 41 patients have died. The Kaplan-Meier estimate and 95 % CI for OS at 5 years was 70 % (53-82 %). Excluding the two patients with recurrent disease at enrollment, 15 of 39 patients progressed or died during follow-up. The Kaplan-Meier estimate and 95 % CI for PFS at 5 years was 66 % (48-78 %). Fifteen patients (37 %) had medical record documentation of lymphedema following treatment. CONCLUSIONS: After additional follow-up, OS and PFS estimates remain high and in-field recurrences low following "sandwich" therapy. The "sandwich" method remains efficacious for women with stage III-IV or recurrent endometrial cancer. PMID- 27408750 TI - The Qatar genome: a population-specific tool for precision medicine in the Middle East. AB - Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual genome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%) and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in QTRG. The benefit for using QTRG varies across ancestries, a factor that should be taken into consideration when selecting an appropriate reference for analysis. PMID- 27408751 TI - Novel mutations in the COL2A1 gene in Japanese patients with Stickler syndrome. AB - Stickler syndrome is an inherited connective tissue disorder that affects the eyes, cartilage and articular tissues. The phenotypes of Stickler syndrome include congenital high myopia, retinal detachment, premature joint degeneration, hearing impairment and craniofacial anomalies, such as cleft palate and midline facial hypoplasia. The disease is genetically heterogeneous, and the majority of the cases are caused by mutations in the COL2A1 gene. We examined 40 Japanese patients with Stickler syndrome from 23 families to determine whether they had mutations in the COL2A1 gene. This analysis was conducted by examining each patient's genomic DNA by Sanger sequencing. Five nonsense, 4 splicing and 8 deletion mutations in the COL2A1 gene were identified, accounting for 21 of the 23 families. Different mutations of the COL2A1 gene were associated with similar phenotypes but with different degrees of expressivity. PMID- 27408752 TI - Novel variation at chr11p13 associated with cystic fibrosis lung disease severity. AB - Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism. PMID- 27408753 TI - Should temporary hemodialysis catheter insertion remain a requirement of nephrology residency training? AB - PURPOSE OF REVIEW: Recently, there has been much debate about the practicality and utility of training nephrology fellows in temporary hemodialysis catheter insertion. SOURCES OF INFORMATION: Literature review along with the authors' opinion. FINDINGS: This skill can be taught easily, in a controlled fashion to maximize success and minimize complications. In order to achieve this training centres should be required to teach using simulation based mastery learning and ultrasound guidance. Employing these strategies makes the inexperienced operator perform at the level of an experienced operator. As a specialty, nephrologists have a responsibility to provide hemodialysis in a timely fashion during emergencies, meaning nephrologists should be able to insert temporary hemodialysis catheters. We should take ownership over this skill and depend on no other specialty. LIMITATIONS: Limited data has been published on this subject. IMPLICATIONS: Temporary hemodialysis catheter insertion should be maintained as a core competency by the Royal College. PMID- 27408754 TI - Percutaneous native renal biopsy adequacy: a successful interdepartmental quality improvement activity. AB - BACKGROUND: An adequate renal biopsy is essential for diagnosis and treatment of medical renal disease. OBJECTIVE: We evaluated two initiatives to improve adequacy of renal biopsy samples at our centre. DESIGN: Retrospective determination of renal biopsy adequacy. SETTING: Queen Elizabeth II Health Sciences Centre. PATIENTS: Patients undergoing medical renal biopsies. MEASUREMENTS: Renal biopsy adequacy. METHODS: The first initiative was to restrict the performance of biopsies to a smaller group of radiologists and to include a comment on biopsy adequacy in every pathology report. The second initiative was to introduce on-site adequacy assessment by a medical laboratory technologist. Native renal and allograft biopsy adequacies were calculated for three periods: 1) baseline, October 2005 to September 2006; 2) after implementation of the first initiative, January 2007 to September 2011; and 3) after implementation of the second initiative, October 2011 to September 2012. A subset of native renal biopsies was examined to determine if there was a relationship between adequacy and number of passes. RESULTS: The percentages of adequate native renal biopsies during the first, second, and third periods were 31%, 72% and 90%, respectively. This represents a significant increase (40%, p < 0.0001) in adequacy following the first initiative, and another significant increase (18%, p = 0.0003) following the second initiative. The percentages of adequate renal allograft biopsies during the first, second, and third periods were 75%, 56% and 69%, respectively. These changes in adequacy were not statistically significant. In the subset of native renal biopsies examined, a biopsy comprising more than three cores was not associated with increase in adequacy. LIMITATIONS: The most important limitation is the lack of generally accepted and applied adequacy criteria limiting generalizability of our findings. CONCLUSIONS: Restricting the performance of biopsies to subspecialist operators, including an adequacy statement in the renal biopsy report and on-site adequacy assessment were effective in significantly improving native renal biopsy adequacy. This improvement appeared unrelated to an increase in the number of passes taken with a biopsy needle. Neither initiative improved the low adequacy of allograft biopsies. PMID- 27408756 TI - Expression patterns of TRalpha and CRABPII genes in Chinese cashmere goat skin during prenatal development. AB - BACKGROUND: The physiologic characteristics of the cashmere trait and many of the differentially expressed genes relevant to hair cycling have been extensively studied, whereas genes involved in the prenatal development of hair follicles have been poorly investigated in cashmere goats. The aim of this study, therefore, was to quantify the time-course changes in the expressions of TRalpha and CRABPII genes in the fetal skin of Chinese cashmere goats at the multiple embryonic days (E70, E75, E80, E90, E100, E120 and E130) using real-time quantitative PCR (RT-qPCR). RESULTS: RT-qPCR showed that TRalpha was expressed at E70 with relatively high level and then slightly decreased (E75, E80, and E90). The highest expression of TRalpha mRNA was revealed at E130 (P > 0.05). The expression pattern of CRABPII mRNA showed an 'up-down-up' trend, which revealed a significantly highest expression at E75 (P < 0.05) and was down-regulated during E80 to E120 (P < 0.05) and mildly increased at E130, subsequently. CONCLUSION: This study demonstrated that TRalpha and CRABPII genes expressed in different levels during prenatal development of cashmere. The present study will be helpful to provide the comprehensive understanding of TRalpha and CRABPII genes expressions during cashmere formation and lay the ground for further studies on their roles in regulation of cashmere growth in goats. PMID- 27408755 TI - Mass screening for chronic kidney disease in rural and remote Canadian first nations people: methodology and demographic characteristics. AB - BACKGROUND: Screening the general population for Chronic Kidney Disease is not currently recommended.. Rural and remote Canadian First Nations people suffer a disproportionate burden of Kidney Failure. The Fi rst N at i ons Community Based S creening to Improve Kidney He alth and Prevent D ialysis ( FINISHED ) project intends to test the hypothesis that a mobile, mass screening initiative available to all First Nations people 10 years of age and older residing in rural and/or remote communities, is feasible, will improve health outcomes and is cost effective. OBJECTIVES: The objective of this manuscript is to describe the key elements required to design, implement and evaluate such a program and describe key characteristics of our screened cohort. DESIGN: Methods and cohort description. SETTING: 11 First Nations communities within 2 Tribal Councils in Manitoba, Canada. PATIENTS: All First Nations individuals between the ages of 10 80 living in the 11communities were eligible for the screening initiative. MEASUREMENTS: Screening Rates achieved within communities. METHODS: An interdisciplinary team partnership was established between the Diabetes Integration Project and the Manitoba Renal Program. Stakeholder consultation was obtained and protocols developed to mass screen community members using point of care testing equipment. All people screened were risk stratified, counselled and referred to nephrologists as required in real time, based on risk. RESULTS: As of August 31, 2014, 1480 people in 11 communities over 2 Tribal Councils have been successfully screened. A mean screening rate of 21% of all community members eligible (aged 10-80) has been achieved. All patients at intermediate or high risk of kidney failure have been seen by nephrologists within 1 month of screening. LIMITATIONS: Long term outcomes of kidney failure rates not assessed for at least 5 years. Alternative public health initiatives to reduce kidney failure not investigated. CONCLUSIONS: Point of care mass screening, real time risk prediction and counselling of First Nations people at high risk of Kidney Failure is feasible in rural and remote communities. Further analysis of this cohort will describe theepidemiology of CKD in these communities, and test the cost effectiveness of this strategy. PMID- 27408757 TI - A mini review on pregnant mothers with cancer: A paradoxical coexistence. AB - The diagnosis of cancer during pregnancy at least in the Western world is a rare phenomenon, but this might be raised into the future due to late pregnancies in the modern societies. The coexistence of pregnancy and cancer implicates numerous medical, ethical, psychological and sometimes religious issues between the mother, the family and the treating physician. Breast, cervical cancer, melanoma and lymphoma are the most common malignancies diagnosed during pregnancy. Diagnostic or therapeutic irradiation requires careful application, whereas systemic chemotherapy is not allowed during the first trimester of pregnancy due to lethal or teratogenic effects as well as to congenital malformations. In some gestational cancers, tumor cells can invade the placenta or the fetus. PMID- 27408758 TI - A review on thyroid cancer during pregnancy: Multitasking is required. AB - Thyroid cancer is the second most common cancer diagnosed during pregnancy after breast cancer. The goal of management is to control malignancy and prevent maternal and fetal complications as a result of maternal hypothyroidism. The role of female sex hormones as an etiologic factor was investigated, with no clear association. Pregnancy can cause an increase in size of a previously existed thyroid nodule through the structural similarity between TSH and BHCG, and the normally expressed estrogen receptors on thyroid gland cells. Effect of pregnancy on development and prognosis of differentiated thyroid malignancies (papillary and follicular) has also been studied. The prognosis of thyroid cancer is not worse in patients diagnosed during pregnancy or those who got pregnant after curative treatment. Termination of pregnancy is not indicated at all, surgery can be delayed till after delivery except in rapidly growing aggressive tumors. While radioactive iodine ablation is absolutely contra-indicated, the new systemic therapies are not well studied during pregnancy. However, almost all these new agents are classified as FDA category C or D and are better to be avoided. The effect of pregnancy on other types of thyroid cancer (medullary and anaplastic thyroid tumors) is not well studied because of very low incidence with pregnancy. The endocrinological management of thyroid cancer during pregnancy is of utmost importance. The hypothyroidism after total thyroidectomy can cause fetal hypothyroidism. Therefore, the management of thyroid cancer related to pregnancy needs a multidisciplinary team. PMID- 27408759 TI - Lung cancer during pregnancy: A narrative review. AB - Lung cancer, the leading cause of cancer deaths in males for decades, has recently become one of commonest causes for women too. As women delay the start of their family, the co-existence of cancer and pregnancy is increasingly observed. Nevertheless, lung cancer during pregnancy remains a rather uncommon condition with less than 70 cases published in recent years. Non-small cell lung carcinoma is the commonest type accounting for about 85% of all cases. Overall survival rates are low. Chemotherapy and/or targeted treatment have been used with poor outcomes. The disease has been also found to affect the products of conception with no short- or long-term consequences for the neonate. This article is referring to a narrative review of lung cancers diagnosed in pregnant women around the world. PMID- 27408760 TI - Review on renal cell carcinoma and pregnancy: A challenging situation. AB - Renal cell carcinoma is rarely diagnosed during pregnancy. Its management is a real challenge due to the sparse literature and lack of standard guidelines. In this situation, the diagnosis is often delayed as the clinical presentation might resemble other pregnancy-related disorders but it should be one of the diagnostic possibilities in women with recurrent or refractory urinary tract symptoms, renal pain, or mass that could be palpated. Diagnostic approach may include ultrasound examination and sometimes magnetic resonance imaging. If localized, surgery would be the preferred line of treatment. Other treatment modalities, end results of treatment, and review of literature of this rare association will be presented. PMID- 27408761 TI - Bone and soft tissue sarcomas during pregnancy: A narrative review of the literature. AB - Bone or soft tissue sarcomas are rarely diagnosed during pregnancy. Until today 137 well documented cases have been reported in the English literature between 1963 and 2014. Thirty-eight pregnant mothers were diagnosed with osteosarcoma, Ewing's sarcoma or chondrosarcoma, whereas 95 other cases of soft tissue sarcomas of various types have been documented. We present the clinical picture and therapeutic management of this coexistence. PMID- 27408762 TI - Hematologic malignancies during pregnancy: A review. AB - Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy. Also, many imaging studies may be hazardous during pregnancy. Management of these malignancies during pregnancy induces many treatment-related risks for mother and baby and should consider patient's preferences for pregnancy continuation. In this article, hematologic malignancies diagnosed in pregnant patients including acute leukemias, chronic myeloid leukemia, lymphomas, multiple myeloma and myeloproliferative neoplasms, will be reviewed, including diagnostic and management strategies and their impact on the pregnant patient and the developing fetus. PMID- 27408763 TI - Biosorptive uptake of Fe(2+), Cu(2+) and As(5+) by activated biochar derived from Colocasia esculenta: Isotherm, kinetics, thermodynamics, and cost estimation. AB - The adsorptive capability of superheated steam activated biochar (SSAB) produced from Colocasia esculenta was investigated for removal of Cu(2+), Fe(2+) and As(5+) from simulated coal mine wastewater. SSAB was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and Brunauer-Emmett Teller analyser. Adsorption isotherm indicated monolayer adsorption which fitted best in Langmuir isotherm model. Thermodynamic study suggested the removal process to be exothermic, feasible and spontaneous in nature. Adsorption of Fe(2+), Cu(2+) and As(5+) on to SSAB was found to be governed by pseudo-second order kinetic model. Efficacy of SSAB in terms of metal desorption, regeneration and reusability for multiple cycles was studied. Regeneration of metal desorbed SSAB with 1 N sodium hydroxide maintained its effectiveness towards multiple metal adsorption cycles. Cost estimation of SSAB production substantiated its cost effectiveness as compared to commercially available activated carbon. Hence, SSAB could be a promising adsorbent for metal ions removal from aqueous solution. PMID- 27408764 TI - Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women. AB - Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47-78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID- 27408765 TI - External fixation is more suitable for intra-articular fractures of the distal radius in elderly patients. AB - The purpose of this study was to compare the functional outcomes, psychological impact, and complication rates associated with external fixation and volar or dorsal plating in relation to the functional parameters following treatment of intra-articular fractures of the distal radius (IFDR) in patients older than 65 years. We hypothesized that using volar or dorsal plating would improve functional outcomes, but that it would be associated with more complications and equivalent functional outcomes when compared with the external fixation group. A total of 123 consecutive patients suffering from IFDR were recruited into the study. The patients were measured for clinical, radiological, and psychosocial functioning outcomes and were followed up after 1 week and 3, 6 and 12 months. After 3 months, the plating group had better pronation (P=0.001), supination, (P=0.047) and extension (P=0.043) scores. These differences were somewhat attenuated by 6 months and disappeared at 1 year. The plating group had a greater occurrence of wound infection (P=0.043), tendonitis, (P=0.024) and additional surgery compared with the external fixation group. The only TNO-AZL Adult Quality of Life scores in the plating group that were lower than those in the external fixation group were in the "gross motor" category (walking upstairs, bending over, walking 500 yards; P=0.023). Internal fixation was more advantageous than external fixation in the early rehabilitation period; after 1 year the outcomes were similar. The plating group showed significantly higher levels of wound infection and tendonitis and had a greater need for additional surgeries. PMID- 27408766 TI - Clinical and genetic findings in a Chinese family with VDR-associated hereditary vitamin D-resistant rickets. AB - Hereditary vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. This disorder is caused by homogeneous or heterogeneous mutations affecting the function of the vitamin D receptor (VDR), which lead to complete or partial target organ resistance to the action of 1,25-dihydroxy vitamin D. A non-consanguineous family of Chinese Han origin with one affected individual demonstrating HVDRR was recruited, with the proband evaluated clinically, biochemically and radiographically. To identify the presence of mutations in the VDR gene, all the exons and exon-intron junctions of the VDR gene from all family members were amplified using PCR and sequenced. The proband showed rickets, progressive alopecia, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. She also suffered from epilepsy, which is rarely seen in patients with HVDRR. Direct sequencing analysis revealed a homozygous missense mutation c.122G>A (p.C41Y) in the VDR gene of the proband, which is located in the first zinc finger of the DNA-binding domain. Both parents had a normal phenotype and were found to be heterozygous for this mutation. We report a Chinese Han family with one individual affected with HVDRR. A homozygous missense mutation c.122G>A (p.C41Y) in the VDR gene was found to be responsible for the patient's syndrome. In contrast to the results of treatment of HVDRR in other patients, our patient responded well to a supplement of oral calcium and a low dose of calcitriol. PMID- 27408767 TI - Cerebral phaeohyphomycosis by Fonsecaea monophora: Report in a patient with AIDS and a ring enhancing lesion. AB - Fungal infections are infrequent causes of brain abscesses. Fonsecaea monophora is a dematiaceous fungus that appears to be neurotropic. We report a case of Fonsecaea monophora infection in a patient with acquired immunodeficiency syndrome, and review previous reports of brain abscesses by this organism. PMID- 27408768 TI - The D-Day of ghrelin. PMID- 27408769 TI - Unforeseen role for glucocorticoids in combinatorial anti-obesity pharmacology. PMID- 27408770 TI - Autonomous interconversion between adult pancreatic alpha-cells and beta-cells after differential metabolic challenges. AB - BACKGROUND: Evidence hints at the ability of beta-cells to emerge from non-beta cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous beta-cell regeneration without genetic or pharmacological manipulations remain to be determined. METHODS & RESULTS: Using PANIC-ATTAC mice, a model of titratable, acute beta-cell apoptosis capable of autonomous, and effective islet mass regeneration, we demonstrate that an extended washout of residual tamoxifen activity is crucial for beta-cell lineage tracing studies using the tamoxifen-inducible Cre/loxP systems. We further establish a doxycycline-inducible system to label different cell types in the mouse pancreas and pursued a highly quantitative assessment to trace adult beta cells after various metabolic challenges. Beyond proliferation of pre-existing beta-cells, non-beta-cells contribute significantly to the post-challenge regenerated beta-cell pool. alpha-cell trans-differentiation is the predominant mechanism upon post-apoptosis regeneration and multiparity. No contributions from exocrine acinar cells were observed. During diet-induced obesity, about 25% of alpha-cells arise de novo from beta-cells. Ectopic expression of Nkx6.1 promotes alpha-to-beta conversion and insulin production. CONCLUSIONS: We identify the origins and fates of adult beta-cells upon post-challenge upon autonomous regeneration of islet mass and establish the quantitative contributions of the different cell types using a lineage tracing system with high temporal resolution. PMID- 27408771 TI - Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets. AB - OBJECTIVE: Complex local crosstalk amongst endocrine cells within the islet ensures tight coordination of their endocrine output. This is illustrated by the recent demonstration that the negative feedback control by delta cells within pancreatic islets determines the homeostatic set-point for plasma glucose during mouse postnatal development. However, the close association of islet endocrine cells that facilitates paracrine crosstalk also complicates the distinction between effects mediated directly on beta cells from indirect effects mediated via local intermediates, such as somatostatin from delta cells. METHODS: To resolve this problem, we generated reporter mice that allow collection of pure pancreatic delta cells along with alpha and beta cells from the same islets and generated comprehensive transcriptomes for each islet endocrine cell type. These transcriptomes afford an unparalleled view of the receptors expressed by delta, alpha and beta cells, and allow the prediction of which signal targets which endocrine cell type with great accuracy. RESULTS: From these transcriptomes, we discovered that the ghrelin receptor is expressed exclusively by delta cells within the islet, which was confirmed by fluorescent in situ hybridization and qPCR. Indeed, ghrelin increases intracellular calcium in delta cells in intact mouse islets, measured by GCaMP6 and robustly potentiates glucose-stimulated somatostatin secretion on mouse and human islets in both static and perfusion assays. In contrast, des-acyl-ghrelin at the same dose had no effect on somatostatin secretion and did not block the actions of ghrelin. CONCLUSIONS: These results offer a straightforward explanation for the well-known insulinostatic actions of ghrelin. Rather than engaging beta cells directly, ghrelin engages delta cells to promote local inhibitory feedback that attenuates insulin release. These findings illustrate the power of our approach to resolve some of the long-standing conundrums with regard to the rich feedback that occurs within the islet that is integral to islet physiology and therefore highly relevant to diabetes. PMID- 27408772 TI - PI3 kinases p110alpha and PI3K-C2beta negatively regulate cAMP via PDE3/8 to control insulin secretion in mouse and human islets. AB - OBJECTIVES: Phosphatidylinositol-3-OH kinase (PI3K) signalling in the endocrine pancreas contributes to glycaemic control. However, the mechanism by which PI3K modulates insulin secretion from the pancreatic beta cell is poorly understood. Thus, our objective was two-fold; to determine the signalling pathway by which acute PI3K inhibition enhances glucose-stimulated insulin secretion (GSIS) and to examine the role of this pathway in islets from type-2 diabetic (T2D) donors. METHODS: Isolated islets from mice and non-diabetic or T2D human donors, or INS 832/13 cells, were treated with inhibitors of PI3K and/or phosphodiesterases (PDEs). The expression of PI3K-C2beta was knocked down using siRNA. We measured insulin release, single-cell exocytosis, intracellular Ca(2+) responses ([Ca(2+)]i) and Ca(2+) channel currents, intracellular cAMP concentrations ([cAMP]i), and activation of cAMP-dependent protein kinase A (PKA) and protein kinase B (PKB/AKT). RESULTS: The non-specific PI3K inhibitor wortmannin amplifies GSIS, raises [cAMP]i and activates PKA, but is without effect in T2D islets. Direct inhibition of specific PDE isoforms demonstrates a role for PDE3 (in humans and mice) and PDE8 (in mice) downstream of PI3K, and restores glucose responsiveness of T2D islets. We implicate a role for the Class II PI3K catalytic isoform PI3K-C2beta in this effect by limiting beta cell exocytosis. CONCLUSIONS: PI3K limits GSIS via PDE3 in human islets. While inhibition of p110alpha or PIK C2beta signalling per se, may promote nutrient-stimulated insulin release, we now suggest that this signalling pathway is perturbed in islets from T2D donors. PMID- 27408773 TI - Lack of AKT in adipocytes causes severe lipodystrophy. AB - OBJECTIVE: Adipose depot mass is tightly regulated to maintain energy homeostasis. AKT is a critical kinase in the insulin-signaling cascade that is required for the process of adipogenesis in vitro. However, the role of AKT in the maintenance and/or function of mature adipocytes in vivo had not been examined. METHODS: To study this, we deleted Akt1 and Akt2 in adipocytes of mice using the AdipoQ-Cre driver. RESULTS: Strikingly, mice lacking adipocyte AKT were severely lipodystrophic, having dramatically reduced gonadal adipose and no discernible subcutaneous or brown adipose tissue. As a result, these mice developed severe insulin resistance accompanied by fatty liver, hepatomegaly and with enlarged islets of Langerhans. CONCLUSIONS: These data reveal the critical role of adipocyte AKT and insulin signaling for maintaining adipose tissue mass. PMID- 27408774 TI - Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue specific insulin receptor ablation. AB - OBJECTIVE: Insulin signaling plays pivotal roles in the development and metabolism of many tissues and cell types. A previous study demonstrated that ablation of insulin receptor (IR) with aP2-Cre markedly reduced adipose tissues mass and protected mice from obesity. However, multiple studies have demonstrated widespread non-adipocyte recombination of floxed alleles in aP2-Cre mice. These findings underscore the need to re-evaluate the role of IR in adipocyte and systemic metabolism with a more adipose tissue-specific Cre mouse line. METHODS: We generated and phenotyped a new adipose tissue-specific IR mouse model using the adipose tissue-specific Adipoq-Cre line. RESULTS: Here we show that the Adipoq-Cre-mediated IR KO in mice leads to lipodystrophy and metabolic dysfunction, which is in stark contrast to the previous study. In contrast to white adipocytes, absence of insulin signaling does not affect development of marrow and brown adipocytes, but instead is required for lipid accumulation particularly for the marrow adipocytes. Lipodystrophic IR KO mice have profound insulin resistance, hyperglycemia, organomegaly, and impaired adipokine secretion. CONCLUSIONS: Our results demonstrate differential roles for insulin signaling for white, brown, and marrow adipocyte development and metabolic regulation. PMID- 27408775 TI - AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue. AB - OBJECTIVE: Characterize the cellular and molecular events responsible for lipodystrophy in AGPAT2 deficient mice. METHODS: Adipose tissue and differentiated MEF were assessed using light and electron microscopy, followed by protein (immunoblots) and mRNA analysis (qPCR). Phospholipid profiling was determined by electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS: In contrast to adult Agpat2 (-/-) mice, fetuses and newborn Agpat2 (-/-) mice have normal mass of white and brown adipose tissue. Loss of both the adipose tissue depots occurs during the first week of postnatal life as a consequence of adipocyte death and inflammatory infiltration of the adipose tissue. At the ultrastructural level, adipose tissue of newborn Agpat2 (-/-) mice is virtually devoid of caveolae and has abnormal mitochondria and lipid droplets. Autophagic structures are also abundant. Consistent with these findings, differentiated Agpat2 (-/-) mouse embryonic fibroblasts (MEFs) also have impaired adipogenesis, characterized by a lower number of lipid-laden cells and ultrastructural abnormalities in lipid droplets, mitochondria and plasma membrane. Overexpression of PPARgamma, the master regulator of adipogenesis, increased the number of Agpat2 (-/-) MEFs that differentiated into adipocyte-like cells but did not prevent morphological abnormalities and cell death. Furthermore, differentiated Agpat2 (-/-) MEFs have abnormal phospholipid compositions with 3-fold increased levels of phosphatidic acid. CONCLUSION: We conclude that lipodystrophy in Agpat2 (-/-) mice results from postnatal cell death of adipose tissue in association with acute local inflammation. It is possible that AGPAT2 deficient adipocytes have an altered lipid filling or a reduced capacity to adapt the massive lipid availability associated with postnatal feeding. PMID- 27408777 TI - G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle. AB - OBJECTIVE: Recent data suggest that adipose triglyceride lipase (ATGL) plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2), recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. METHODS: We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. RESULTS: G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05) while G0S2 knockdown strongly reduces (-68%, p < 0.001) triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4) expression (5.4 fold, p < 0.001). Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro. CONCLUSION: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism. PMID- 27408776 TI - Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. AB - OBJECTIVE: A novel approach to regulate obesity-associated adipose inflammation may be through metabolic reprogramming of macrophages (MPhis). Broadly speaking, MPhis dependent on glucose are pro-inflammatory, classically activated MPhis (CAM), which contribute to adipose inflammation and insulin resistance. In contrast, MPhis that primarily metabolize fatty acids are alternatively activated MPhis (AAM) and maintain tissue insulin sensitivity. In actuality, there is much flexibility and overlap in the CAM-AAM spectrum in vivo dependent upon various stimuli in the microenvironment. We hypothesized that specific lipid trafficking proteins, e.g. fatty acid transport protein 1 (FATP1), would direct MPhi fatty acid transport and metabolism to limit inflammation and contribute to the maintenance of adipose tissue homeostasis. METHODS: Bone marrow derived MPhis (BMDMs) from Fatp1 (-/-) and Fatp1 (+/+) mice were used to investigate FATP1 dependent substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. We also generated C57BL/6J chimeric mice by bone marrow transplant specifically lacking hematopoetic FATP1 (Fatp1 (B-/-)) and controls Fatp1 (B+/+). Mice were challenged by high fat diet (HFD) or low fat diet (LFD) and analyses including MRI, glucose and insulin tolerance tests, flow cytometric, histologic, and protein quantification assays were conducted. Finally, an FATP1 overexpressing RAW 264.7 MPhi cell line (FATP1-OE) and empty vector control (FATP1-EV) were developed as a gain of function model to test effects on substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. RESULTS: Fatp1 is downregulated with pro-inflammatory stimulation of MPhis. Fatp1 (-/-) BMDMs and FATP1-OE RAW 264.7 MPhis demonstrated that FATP1 reciprocally controled metabolic flexibility, i.e. lipid and glucose metabolism, which was associated with inflammatory response. Supporting our previous work demonstrating the positive relationship between glucose metabolism and inflammation, loss of FATP1 enhanced glucose metabolism and exaggerated the pro-inflammatory CAM phenotype. Fatp1 (B-/-) chimeras fed a HFD gained more epididymal white adipose mass, which was inflamed and oxidatively stressed, compared to HFD-fed Fatp1 (B+/+) controls. Adipose tissue macrophages displayed a CAM-like phenotype in the absence of Fatp1. Conversely, functional overexpression of FATP1 decreased many aspects of glucose metabolism and diminished CAM-stimulated inflammation in vitro. FATP1 displayed acyl-CoA synthetase activity for long chain fatty acids in MPhis and modulated lipid mediator metabolism in MPhis. CONCLUSION: Our findings provide evidence that FATP1 is a novel regulator of MPhi activation through control of substrate metabolism. Absence of FATP1 exacerbated pro-inflammatory activation in vitro and increased local and systemic components of the metabolic syndrome in HFD-fed Fatp1 (B-/-) mice. In contrast, gain of FATP1 activity in MPhis suggested that Fatp1-mediated activation of fatty acids, substrate switch to glucose, oxidative stress, and lipid mediator synthesis are potential mechanisms. We demonstrate for the first time that FATP1 provides a unique mechanism by which the inflammatory tone of adipose and systemic metabolism may be regulated. PMID- 27408778 TI - Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl glycine export. AB - OBJECTIVE: A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. METHODS: Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES). We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism. RESULTS: LF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH), was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp. CONCLUSIONS: Our data are consistent with a model wherein elevated circulating BCAA contribute to development of obesity related insulin resistance by interfering with lipid oxidation in skeletal muscle. BCAA-dependent lowering of the skeletal muscle glycine pool appears to contribute to this effect by slowing acyl-glycine export to the urine. PMID- 27408779 TI - Limiting glucocorticoid secretion increases the anorexigenic property of Exendin 4. AB - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) analogs are attractive options for the treatment of type II diabetes and obesity because of their incretin and anorexigenic effects. Peripheral administration of the GLP-1R agonist Exendin-4 (Ex-4) also increases glucocorticoid secretion in rodents and humans, but whether the released glucocorticoids interact with Ex-4's anorexigenic effect remains unclear. METHODS: To test this, we used two experimental approaches that suppress corticosterone secretion and then assessed Ex-4 effects on eating in adult male rats. First, we combined acute and chronic low dose dexamethasone treatment with Ex-4. Second, we ablated hindbrain catecholamine neurons projecting to the hypothalamus with anti-dopamine-beta-hydroxylase-saporin (DSAP) to block Ex-4 induced corticosterone secretion. RESULTS: Combining dexamethasone and Ex-4 produced a larger acute anorexigenic effect than Ex-4 alone. Likewise, chronic dexamethasone and Ex-4 co-treatment produced a synergistic effect on eating and greater body weight loss in diet-induced obese rats than Ex-4 alone. DSAP lesions not only blunted Ex-4's ability to increase corticosterone secretion, but potentiated the anorexigenic effect of Ex-4, indicating that Ex-4-dependent corticosterone secretion opposes Ex-4's actions. Consistent with the enhancement of Ex-4's anorexigenic effect, DSAP lesion altered Ex-4-dependent changes in neuropeptide Y, preproglucagon, and corticotropin releasing hormone gene expression involved in glucocorticoid feedback. CONCLUSIONS: Our findings demonstrate that limiting glucocorticoid secretion and actions with low dose dexamethasone or DSAP lesion increases Ex-4's ability to reduce food intake and body weight. Novel glucocorticoid receptor based mechanisms, therefore, may help enhance GLP-1-based obesity therapies. PMID- 27408781 TI - PGC-1alpha expression in murine AgRP neurons regulates food intake and energy balance. AB - OBJECTIVE: Food intake and whole-body energy homeostasis are controlled by agouti related protein (AgRP) and pro-opiomelanocortin (POMC) neurons located in the arcuate nucleus of the hypothalamus. Key energy sensors, such as the AMP activated protein kinase (AMPK) or sirtuin 1 (SIRT1), are essential in AgRP and POMC cells to ensure proper energy balance. In peripheral tissues, the transcriptional coactivator PGC-1alpha closely associates with these sensors to regulate cellular metabolism. The role of PGC-1alpha in the ARC nucleus, however, remains unknown. METHODS: Using AgRP and POMC neurons specific knockout (KO) mouse models we studied the consequences of PGC-1alpha deletion on metabolic parameters during fed and fasted states and on ghrelin and leptin responses. We also took advantage of an immortalized AgRP cell line to assess the impact of PGC 1alpha modulation on fasting induced AgRP expression. RESULTS: PGC-1alpha is dispensable for POMC functions in both fed and fasted states. In stark contrast, mice carrying a specific deletion of PGC-1alpha in AgRP neurons display increased adiposity concomitant with significantly lower body temperature and RER values during nighttime. In addition, the absence of PGC-1alpha in AgRP neurons reduces food intake in the fed and fasted states and alters the response to leptin. Finally, both in vivo and in an immortalized AgRP cell line, PGC-1alpha modulates AgRP expression induction upon fasting. CONCLUSIONS: Collectively, our results highlight a role for PGC-1alpha in the regulation of AgRP neuronal functions in the control of food intake and peripheral metabolism. PMID- 27408780 TI - Melanocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss. AB - OBJECTIVE: Appetitive responses to weight loss are mediated by a nutrient-sensing neural network comprised of melanocortin neurons. The role of neural melanocortin 3 receptors (MC3R) in mediating these responses is enigmatic. Mc3r knockout mice exhibit a paradoxical phenotype of obesity and reduced feeding-related behaviors in situations of nutrient scarcity. Here we examined whether MC3Rs expressed in mesolimbic neurons regulate feeding-related motivational responses. METHODS: Interactions between Mc3r genotype, cognitive function and energy balance on food self-administration were assessed using operant conditioning with fixed- and progressive ratio (FR1/PR1) settings. Inhibition of Mc3r transcription by a loxP flanked transcriptional blocker (TB) in C57BL/6JN mice (Mc3r (TB/TB) ) was reversed in mesolimbic neurons using DAT-Cre (DAT-MC3R). RESULTS: Caloric restriction (CR) caused 10-15% weight loss and increased motivation to acquire food rewards during training sessions. c-Fos-expression in the nucleus accumbens was increased 1 h following food presentation. While exhibiting weight loss, total food self-administration, enhanced motivation to self-administer food rewards in training sessions held during CR and c-Fos-activation in the nucleus accumbens following re-feeding were all markedly attenuated in Mc3r (TB/TB) mice. In contrast, cognitive abilities were normal in Mc3r (TB/TB) mice. Total food self-administration during FR1 sessions was not rescued in DAT-MC3R mice, however enhanced motivational responses to self-administer food rewards in PR1 conditions were restored. The nutrient-partitioning phenotype observed with Mc3r-deficiency was not rescued in DAT-MC3R mice. CONCLUSIONS: Mesolimbic MC3Rs mediate enhanced motivational responses during CR. However, they are insufficient to restore normal caloric loading when food is presented during CR and do not affect metabolic conditions altering nutrient partitioning. PMID- 27408782 TI - Immunoglobulin G4-related pleuritis - A case report. AB - Immunoglobulin G4-related disease (IgG4-RD) is a chronic disease that presents with inflammation and fibrosis of involved tissue. It encompasses several disorders previously described using different terms, but all disorders are characterised by IgG4-positive plasma cells and lymphocytes infiltration of tissues. We report a rare case of a 58-year-old man with IgG4-related pleural disease without other systemic manifestations. The diagnosis was based on characteristic changes on PET-CT and typical histopathology in a pleural specimen. The patient's condition improved following immunosuppressive therapy. PMID- 27408784 TI - Bronchiolitis obliterans organizing pneumonia associated with achalasia: A case report. AB - There is little mention in the literature about achalasia as an etiologic factor of Bronchiolitis obliterans organizing pneumonia (BOOP). In this study, a case of BOOP, which appeared to be secondary to achalasia is reported. A 35 years old man present with nonproductive cough, chills and fever from two month ago. Due to permanent consolidation in mid zone of right lung and unresponsive to antibiotics, transthoracic needle biopsy was done that showed BOOP. Due to esophageal dilatation in chest computerized tomography (CT) scan, endoscopy and esophagogram was done that showed achalasia. After surgery and a course of corticosteroid the patient condition became well. This report demonstrates that achalasia may be associated with BOOP. PMID- 27408783 TI - Acute eosinophilic pneumonia caused by camostat mesilate: The first case report. AB - Camostat mesilate is in widespread clinical use mainly to treat chronic pancreatitis, and drug-induced lung injury has not been previously reported. However, pulmonary infiltration with peripheral blood eosinophilia appeared after taking camostat mesilate for ten days. The histological findings showed eosinophilic infiltration into the alveolar space and interstitum, and drug lymphocyte stimulation test of peripheral blood was positive. Both peripheral blood eosinophilia and pulmonary involvements improved two weeks later with the cessation of this drug. To the best of our knowledge, this case is the first report of camostat mesilate-induced acute eosinophilic pneumonia. PMID- 27408785 TI - Pulmonary arterial hypertension secondary to adult-onset Still's disease: Response to cyclosporine and sildenafil over 15 years of follow-up. AB - Adult onset Still's disease (AOSD) is an autoimmune disease characterized by systemic inflammation and is a rarely reported cause of pulmonary arterial hypertension (PAH). We describe the clinical course of a 40-year-old woman who presented with PAH 19 months after a diagnosis of AOSD. Sildenafil and immunosuppressive therapy with cyclosporine resulted in clinical and hemodynamic improvement with long-term survival 15 years after her initial presentation of AOSD. We review the literature for published cases of PAH due to AOSD and discuss the potential mechanisms relating inflammatory diseases and PAH. PMID- 27408786 TI - Acute respiratory distress syndrome due to severe pulmonary tuberculosis treated with extracorporeal membrane oxygenation: A case report and review of the literature. AB - Mortality in patients with pulmonary tuberculosis remains high, especially in those who develop acute respiratory distress syndrome (ARDS). We report on a-48 year-old man with ARDS due to severe pulmonary tuberculosis who was rescued by extracorporeal membrane oxygenation (ECMO). He was initially hospitalized in the intensive care unit and noninvasive positive-pressure ventilation started. He was also administered anti-tuberculosis drugs and received systemic corticosteroid therapy. Six days later, further deterioration of gas exchange prompted the decision to intubate. However, he experienced progressive deterioration of arterial oxygenation despite conventional ventilatory support. We therefore decided to administer ECMO on day 9. After initiation of these treatments and ECMO support, pulmonary infiltrate and oxygenation status gradually improved and ECMO was discontinued on day 52. The patient was finally discharged from our hospital without severe disability. ECMO should be considered one of the treatment options for the management of ARDS due to severe pulmonary tuberculosis. PMID- 27408787 TI - Pulmonary alveolar proteinosis and Niemann Pick disease type B: An unexpected combination. AB - BACKGROUND: Pulmonary involvement in Niemann-Pick disease (NPD) is a common finding, especially in type B. It usually manifests with symptoms of restrictive lung disease appearing in adulthood but showing gradual deterioration over time. Treatment options have been dramatically limited, with whole lung lavage offering only temporary improvement. Pulmonary alveolar proteinosis (PAP) has been previously mentioned as part of lung disease in NPD, but only in rare cases of type C2. This is the first study that reports the coexistence of autoimmune PAP with NPD type B. CASE PRESENTATION: An 8 year old female patient with the diagnosis of NPD type B and a 2-year history of respiratory symptoms, presented with another episode of severe respiratory distress. Chest imaging revealed a "crazy paving pattern", raising concern for PAP. After admission to the intensive care unit and application of non-invasive positive pressure ventilation, a whole lung lavage was performed with return of a milky-appearing proteinaceous fluid. Her status post-lavage was markedly improved, while genetic testing placed the diagnosis of autoimmune PAP. The patient was initiated on inhaled GM-CSF treatment and shows a beneficial outcome to date. CONCLUSIONS: In spite of the patient's symptoms being consistent with NPD type of lung involvement, clinical findings raised the suspicion of an underlying disorder, which surprisingly proved to be PAP. The detection of anti-GM-CSF autoantibodies in our patient allowed the initiation of inhaled GM-CSF treatment, which is likely to prove more beneficial in her prognosis than repeated lung lavages. PMID- 27408788 TI - Acute myeloid leukemia in the older adults. AB - AML is an aggressive hematological malignancy with highest incidence in the older adults. The adverse features of AML in the elderly, and the frailties and comorbidities frequently present in them, make their management a particularly difficult therapeutic challenge. In this context, it is important to assess carefully patient- as well as disease-associated prognostic features with validated tools. The fittest patients should be considered for curative therapy, such as bone marrow transplantation, whereas low intensity options may be more appropriate for frail patients. Here we review how to assess patients with elderly AML and the treatments options available for them. PMID- 27408789 TI - Occupancy of pramipexole (Sifrol) at cerebral dopamine D2/3 receptors in Parkinson's disease patients. AB - Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 * 0.7 mg p.d.), and again at a later date, after withholding pramipexole 48-72 h (OFF-Sifrol); in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ? 0.01) occupancy at [(18)F]fallypride binding sites in globus pallidus (8%) thalamus (9%) and substantia nigra (19%), as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum. PMID- 27408790 TI - Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry. AB - A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP) consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure. PMID- 27408791 TI - Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network. AB - The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network is an ongoing multi-center collaborative research group established to conduct integrated studies in participants with urologic chronic pelvic pain syndrome (UCPPS). The goal of these investigations is to provide new insights into the etiology, natural history, clinical, demographic and behavioral characteristics, search for new and evaluate candidate biomarkers, systematically test for contributions of infectious agents to symptoms, and conduct animal studies to understand underlying mechanisms for UCPPS. Study participants were enrolled in a one-year observational study and evaluated through a multisite, collaborative neuroimaging study to evaluate the association between UCPPS and brain structure and function. 3D T1-weighted structural images, resting-state fMRI, and high angular resolution diffusion MRI were acquired in five participating MAPP Network sites using 8 separate MRI hardware and software configurations. We describe the neuroimaging methods and procedures used to scan participants, the challenges encountered in obtaining data from multiple sites with different equipment/software, and our efforts to minimize site-to-site variation. PMID- 27408792 TI - Cortical amyloid burden and age moderate hippocampal activity in cognitively normal adults. AB - Neurodegeneration in the medial temporal lobe, particularly in the hippocampus, is viewed as the primary source of AD-related memory deficits. Yet, in the earliest preclinical phase of Alzheimer's disease (AD), amyloid-beta (Abeta) plaques deposit primarily in the neocortex, not in the medial temporal lobe. Tau tangles, however, do often aggregate in the medial temporal lobe in parallel with amyloid deposition in the neocortex in AD. In the present study, we focused on the relationship between cortical amyloid deposition and hippocampal activity during a memory-encoding task in a sample of cognitively-normal elderly aged 60 89. We hypothesized that age would moderate the Abeta effect on hippocampal activity, and could explain some of the mixed findings in the literature. We report that high cortical Abeta load was associated with lower task-related hippocampal activity during memory encoding. Importantly, this relationship was found more evident in the younger elderly, even after controlling for subsequent recognition memory of the in-scanner task and a general episodic memory construct score. Furthermore, regional cerebrovascular reactivity measured in a subset of participants showed little role in modifying the age-dependent Abeta effect on hippocampal activity. Our findings support the idea that age is an important variable in understanding hippocampal function in preclinical AD. PMID- 27408793 TI - Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model. PMID- 27408794 TI - Cerebral white matter structure is associated with DSM-5 schizophrenia symptom dimensions. AB - Diffusion tensor imaging (DTI) studies have provided evidence of widespread white matter (WM) abnormalities in schizophrenia. Although these abnormalities appear clinically significant, the relationship to specific clinical symptoms is limited and heterogeneous. This study examined the association between WM microstructure and the severity of the five main DSM-5 schizophrenia symptom dimensions. DTI was measured in forty patients with schizophrenia spectrum disorders. Using Tract Based Spatial Statistics controlling for age, gender and antipsychotic dosage, our analyses revealed significant negative relationships between WM microstructure and two DSM-5 symptom dimensions: Whereas abnormal psychomotor behavior was particularly related to WM of motor tracts, negative symptoms were associated with WM microstructure of the prefrontal and right temporal lobes. However, we found no associations between WM microstructure and delusions, hallucinations or disorganized speech. These data highlight the relevance of characteristic WM disconnectivity patterns as markers for negative symptoms and abnormal psychomotor behavior in schizophrenia and provide evidence for relevant associations between brain structure and aberrant behavior. PMID- 27408795 TI - Connectome-scale assessment of structural and functional connectivity in mild traumatic brain injury at the acute stage. AB - Mild traumatic brain injury (mTBI) accounts for over one million emergency visits each year in the United States. The large-scale structural and functional network connectivity changes of mTBI are still unknown. This study was designed to determine the connectome-scale brain network connectivity changes in mTBI at both structural and functional levels. 40 mTBI patients at the acute stage and 50 healthy controls were recruited. A novel approach called Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOLs) was applied for connectome-scale analysis of both diffusion tensor imaging and resting state functional MRI data. Among 358 networks identified on DICCCOL analysis, 41 networks were identified as structurally discrepant between patient and control groups. The involved major white matter tracts include the corpus callosum, and superior and inferior longitudinal fasciculi. Functional connectivity analysis identified 60 connectomic signatures that differentiate patients from controls with 93.75% sensitivity and 100% specificity. Analysis of functional domains showed decreased intra-network connectivity within the emotion network and among emotion-cognition interactions, and increased interactions among action-emotion and action-cognition as well as within perception networks. This work suggests that mTBI may result in changes of structural and functional connectivity on a connectome scale at the acute stage. PMID- 27408796 TI - Cortical thickness in relation to clinical symptom onset in preclinical AD. AB - Mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia are preceded by a phase of disease, referred to as 'preclinical AD', during which cognitively normal individuals have evidence of AD pathology in the absence of clinical impairment. This study examined whether a magnetic resonance imaging (MRI) measure of cortical thickness in brain regions, collectively known as 'AD vulnerable' regions, predicted the time to onset of clinical symptoms associated with MCI and whether cortical thickness was similarly predictive of clinical symptom onset within 7 years post baseline versus progression at a later point in time. These analyses included 240 participants from the BIOCARD study, a cohort of longitudinally followed individuals who were cognitively normal at the time of their MRI (mean age = 56 years). Participants have been followed for up to 18 years (M follow-up = 11.8 years) and 50 participants with MRIs at baseline have developed MCI or dementia over time (mean time to clinical symptom onset = 7 years). Cortical thickness in AD vulnerable regions was based on the mean thickness of eight cortical regions. Using Cox regression models, we found that lower mean cortical thickness was associated with an increased risk of progression from normal cognition to clinical symptom onset within 7 years of baseline (p = 0.03), but not with progression > 7 years from baseline (p = 0.30). Lower cortical thickness was also associated with higher levels of phosphorylated tau, measured in cerebrospinal fluid at baseline. These results suggest that cortical thinning in AD vulnerable regions is detectable in cognitively normal individuals several years prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI, and that the changes are more likely to be evident in the years proximal to clinical symptom onset, consistent with hypothetical AD biomarker models. PMID- 27408797 TI - Patterns of white matter damage are non-random and associated with cognitive function in secondary progressive multiple sclerosis. AB - In multiple sclerosis (MS), white matter damage is thought to contribute to cognitive dysfunction, which is especially prominent in secondary progressive MS (SPMS). While studies in healthy subjects have revealed patterns of correlated fractional anisotropy (FA) across white matter tracts, little is known about the underlying patterns of white matter damage in MS. In the present study, we aimed to map the SPMS-related covariance patterns of microstructural white matter changes, and investigated whether or not these patterns were associated with cognitive dysfunction. Diffusion MRI was acquired from 30 SPMS patients and 32 healthy controls (HC). A tensor model was fitted and FA maps were processed using tract-based spatial statistics (TBSS) in order to obtain a skeletonised map for each subject. The skeletonised FA maps of patients only were decomposed into 18 spatially independent components (ICs) using independent component analysis. Comprehensive cognitive assessment was conducted to evaluate five cognitive domains. Correlations between cognitive performance and (1) severity of FA abnormalities of the extracted ICs (i.e. z-scores relative to FA values of HC) and (2) IC load (i.e. FA covariance of a particular IC) were examined. SPMS patients showed lower FA values of all examined patterns of correlated FA (i.e. spatially independent components) than HC (p < 0.01). Tracts visually assigned to the supratentorial commissural class were most severely damaged (z = - 3.54; p < 0.001). Reduced FA was significantly correlated with reduced IC load (i.e. FA covariance) (r = 0.441; p < 0.05). Lower mean FA and component load of the supratentorial projection tracts and limbic association tracts classes were associated with worse cognitive function, including executive function, working memory and verbal memory. Despite the presence of white matter damage, it was possible to reveal patterns of FA covariance across SPMS patients. This could indicate that white matter tracts belonging to the same cluster, and thus with similar characteristics, tend to follow similar trends during neurodegeneration. Furthermore, these underlying FA patterns might help to explain cognitive dysfunction in SPMS. PMID- 27408798 TI - DEMARCATE: Density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer. AB - Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher-Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques. PMID- 27408800 TI - Reduced helminth parasitism in the introduced bank vole (Myodes glareolus): More parasites lost than gained. AB - Introduced species are often less parasitised compared to their native counterparts and to ecologically similar hosts in the new environment. Reduced parasitism may come about due to both the loss of original parasites and low acquisition of novel parasites. In this study we investigated the intestinal helminth parasites of the introduced bank vole (Myodes glareolus) in Ireland. Results were compared to data from other European studies and to the intestinal helminth fauna of an ecologically similar native rodent in Ireland, the wood mouse (Apodemus sylvaticus). The helminth fauna of introduced bank voles exhibited low diversity with only 3 species recovered: Aspiculuris tianjinensis; Aonchotheca murissylvatici and Taenia martis larvae. In particular, no adult parasites with indirect life-cycles were found in bank voles suggesting that indirectly transmitted parasites are less likely to establish in invasive hosts. Also, the results of this study add support to the enemy release hypothesis. PMID- 27408801 TI - Gray fox (Urocyon cinereoargenteus) parasite diversity in central Mexico. AB - Mexico has a long history of parasitological studies in communities of vertebrates. However, the mega diversity of the country makes fauna inventories an ongoing priority. Presently, there is little published on the parasite fauna of gray foxes (Urocyon cinereoargenteus Schereber, 1775) and this study provides new records of parasites for gray foxes in central Mexico. It is a continuation of a series of previous parasitological studies conducted with this carnivore in Mexico from 2003 to the present. A total of 24 foxes in the Parque Nacional El Cimatario (PANEC) were trapped, anaesthetized, and parasites recovered. The species found were Dirofilaria immitis, Ctenocephalides canis, C. felis, Euhoplopsillus glacialis affinis (first report for gray foxes in Mexico) Pulex simulants, and Ixodes sp. Three additional gray fox carcasses were necropsied and the parasites collected were adult nematodes Physaloptera praeputialis and Toxocara canis. The intensive study of the gray fox population selected for the 2013-2015 recent period allowed for a two-fold increase in the number of parasite species recorded for this carnivore since 2003 (nine to 18 parasite species), mainly recording parasitic arthropods, Dirofilaria immitis filariae and adult nematodes. The parasite species recorded are generalists that can survive in anthropic environments; which is characteristic of the present ecological scenario in central Mexico. The close proximity of the PANEC to the city of Santiago de Queretaro suggests possible parasite transmission between the foxes and domestic and feral dogs. Furthermore, packs of feral dogs in the PANEC might have altered habitat use by foxes, with possible impacts on transmission. PMID- 27408799 TI - Antiretroviral therapy affects the z-score index of deviant cortical EEG rhythms in naive HIV individuals. AB - OBJECTIVE: Here we tested the effect of combined antiretroviral therapy (cART) on deviant electroencephalographic (EEG) source activity in treatment-naive HIV individuals. METHODS: Resting state eyes-closed EEG data were recorded before and after 5 months of cART in 48 male HIV subjects, who were naive at the study start. The EEG data were also recorded in 59 age- and sex-matched healthy subjects as a control group. Frequency bands of interest included delta, theta, alpha1, alpha2 and alpha3, based on alpha frequency peak specific to each individual. They also included beta1 (13-20 Hz) and beta2 (20-30 Hz). Low resolution brain electromagnetic tomography (LORETA) estimated EEG cortical source activity in frontal, central, temporal, parietal, and occipital regions. RESULTS: Before the therapy, the HIV group showed greater parietal delta source activity and lower spatially diffuse alpha source activity compared to the control group. Thus, the ratio of parietal delta and alpha3 source activity served as an EEG marker. The z-score showed a statistically deviant EEG marker (EEG +) in 50% of the HIV individuals before therapy (p < 0.05). After 5 months of cART, delta source activity decreased, and alpha3 source activity increased in the HIV subjects with EEG + (about 50% of them showed a normalized EEG marker). CONCLUSIONS: This procedure detected a deviant EEG marker before therapy and its post-therapy normalization in naive HIV single individuals. SIGNIFICANCE: The parietal delta/alpha3 EEG marker may be used to monitor cART effects on brain function in such individuals. PMID- 27408802 TI - Intraoperative mapping of expressive language cortex using passive real-time electrocorticography. AB - In this case report, we investigated the utility and practicality of passive intraoperative functional mapping of expressive language cortex using high resolution electrocorticography (ECoG). The patient presented here experienced new-onset seizures caused by a medium-grade tumor in very close proximity to expressive language regions. In preparation of tumor resection, the patient underwent multiple functional language mapping procedures. We examined the relationship of results obtained with intraoperative high-resolution ECoG, extraoperative ECoG utilizing a conventional subdural grid, extraoperative electrical cortical stimulation (ECS) mapping, and functional magnetic resonance imaging (fMRI). Our results demonstrate that intraoperative mapping using high resolution ECoG is feasible and, within minutes, produces results that are qualitatively concordant to those achieved by extraoperative mapping modalities. They also suggest that functional language mapping of expressive language areas with ECoG may prove useful in many intraoperative conditions given its time efficiency and safety. Finally, they demonstrate that integration of results from multiple functional mapping techniques, both intraoperative and extraoperative, may serve to improve the confidence in or precision of functional localization when pathology encroaches upon eloquent language cortex. PMID- 27408804 TI - Status epilepticus caused by cerebral amyloid angiopathy-related inflammation. AB - This report discusses a case of nonconvulsive status epilepticus, caused by cerebral amyloid angiopathy-related inflammation. Brain biopsy demonstrated cerebral amyloid angiopathy, with clinical and radiographic features indicative of a fluctuating inflammatory process. Immunomodulatory treatment with pulse steroids resulted in rapid and dramatic clinical and radiographic improvement. Cerebral amyloid angiopathy-related inflammation should be considered in the differential diagnosis of new-onset seizures after the age of 40, when associated with fluctuating multifocal T2 hyperintensities and petechial hemorrhages on gradient echo (GRE) or susceptibility-weighted (SWI) MRI sequences. PMID- 27408803 TI - Electrocorticographic mapping of expressive language function without requiring the patient to speak: A report of three cases. AB - OBJECTIVE: Patients requiring resective brain surgery often undergo functional brain mapping during perioperative planning to localize expressive language areas. Currently, all established protocols to perform such mapping require substantial time and patient participation during verb generation or similar tasks. These issues can make language mapping impractical in certain clinical circumstances (e.g., during awake craniotomies) or with certain populations (e.g., pediatric patients). Thus, it is important to develop new techniques that reduce mapping time and the requirement for active patient participation. Several neuroscientific studies reported that the mere auditory presentation of speech stimuli can engage not only receptive but also expressive language areas. Here, we tested the hypothesis that submission of electrocorticographic (ECoG) recordings during a short speech listening task to an appropriate analysis procedure can identify eloquent expressive language cortex without requiring the patient to speak. METHODS: Three patients undergoing temporary placement of subdural electrode grids passively listened to stories while we recorded their ECoG activity. We identified those sites whose activity in the broadband gamma range (70-170 Hz) changed immediately after presentation of the speech stimuli with respect to a prestimulus baseline. RESULTS: Our analyses revealed increased broadband gamma activity at distinct locations in the inferior frontal cortex, superior temporal gyrus, and/or perisylvian areas in all three patients and premotor and/or supplementary motor areas in two patients. The sites in the inferior frontal cortex that we identified with our procedure were either on or immediately adjacent to locations identified using electrical cortical stimulation (ECS) mapping. CONCLUSIONS: The results of this study provide encouraging preliminary evidence that it may be possible that a brief and practical protocol can identify expressive language areas without requiring the patient to speak. This protocol could provide the clinician with a map of expressive language cortex within a few minutes. This may be useful as an adjunct to ECS interrogation or as an alternative to mapping using functional magnetic resonance imaging (fMRI). In conclusion, with further development and validation in more subjects, the approach presented here could help in identifying expressive language areas in situations where patients cannot speak in response to task instructions. PMID- 27408805 TI - Nonconvulsive status epilepticus cases arising in connection with cephalosporins. AB - Cephalosporins, particularly cefepime, exert neurotoxic side effects that can lead to status epilepticus. These neurotoxic side effects include myoclonus, dystonic movements, tremor, asterixis, seizure, status epilepticus, encephalopathy, and sometimes coma. Status epilepticus, particularly nonconvulsive status epilepticus (NCSE), is a well-known but unusual complication in patients with altered renal function who were receiving treatment with intravenous cephalosporins, especially cefepime. We reviewed the clinical and electroencephalographic (EEG) characteristics of 7 patients with renal failure who developed consciousness alterations with changes in EEG activity while being treated with cephalosporins. All patients developed renal failure: six patients had chronic renal failure, one patient had acute renal failure, and two patients were administered hemodialysis. Nonconvulsive status epilepticus was observed between 2 and 8 days (average of 5.6 days) after initiation of cephalosporins. Cephalosporins are epileptogenic drugs, especially when used in excessive doses or when renal function is impaired. Critically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Clinical and electrophysiological results of patients guide the diagnosis of NCSE by healthcare providers. PMID- 27408806 TI - De novo transcriptome assembly of 'Angeleno' and 'Lamoon' Japanese plum cultivars (Prunus salicina). AB - Japanese plum (Prunus salicina L.) is a fruit tree of the Rosaceae family, which is an economically important stone fruit around the world. Currently, Japanese plum breeding programs combine traditional breeding and plant physiology strategies with genetic and genomic analysis. In order to understand the flavonoid pathway regulation and to develop molecular markers associated to the fuit skin color (EST-SSRs), we performed a next generation sequencing based on Illumina Hiseq2000 platform. A total of 22.4 GB and 21 GB raw data were obtained from 'Lamoon' and 'Angeleno' respectively, corresponding to 85,404,726 raw reads to 'Lamoon' and 79,781,666 to 'Angeleno'. A total of 139,775,975 reads were filtered after removing low-quality reads and trimming the adapter sequences. De novo transcriptome assembly was performed using CLC Genome Workbench software and a total of 54,584 unique contigs were generated, with an N50 of 1343 base pair (bp) and a mean length of 829 bp. This work contributed with a specific Japanese plum skin transcriptome, providing two libraries of contrasting fruit skin color phenotype (yellow and red) and increasing substantially the GB of raw data available until now for this specie. PMID- 27408807 TI - Transcriptional profiling of foam cells in response to hypercholesterolemia. AB - Hypercholesterolemia is a main risk factor for atherosclerosis development. Arterial macrophages, or foam cells, take-up and process lipoprotein particles deposited in arteries, and store much of the cholesterol carried by these particles in their cytoplasm. However, the effects of exposure to different cholesterol levels on foam cells remain poorly understood. Given the remarkable plasticity of macrophages in response to environmental variables, studies on macrophage biology should ideally be performed in the environment where they exert their physiological functions, namely atherosclerotic lesions in the case of foam cells. We used a mouse model of atherosclerosis, the apolipoprotein E deficient mouse, to study in vivo the transcriptional response of foam cells to short- and long-term elevations in plasma cholesterol, induced by feeding mice a western type diet. The microarray data sets from this study have been deposited in NCBI's Gene Expression Omnibus under the accession number GSE70619. Here we provide detailed information on the experimental set-up, on the isolation of RNA by laser capture microdissection, and on the methodology used for RNA amplification and analysis by microarray and quantitative real-time PCR. PMID- 27408808 TI - Gene expression analysis of Solanum lycopersicum and Solanum habrochaites under drought conditions. AB - Drought is one of the limiting environmental factors that affect crop production worldwide. Understanding the molecular mechanism of drought stress is the key to developing drought tolerant crop. In this experiment we performed expression profiling of tomato plants under water deficit conditions using microarray technology. The data set we generated (available in the NCBI/GEO database under GSE22304) has been analyzed to identify genes that are involved in the regulation of tomato's responses to drought. PMID- 27408809 TI - Comparative transcriptome analysis of ginger variety Suprabha from two different agro-climatic zones of Odisha. AB - Ginger (Zingiber officinale Rosc.), a well-known member of family Zingiberaceae, is bestowed with number of medicinal properties which is because of the secondary metabolites, essential oil and oleoresin, it contains in its rhizome. The drug yielding potential is known to depend on agro-climatic conditions prevailing at the place cultivation. Present study deals with comparative transcriptome analysis of two sample of elite ginger variety Suprabha collected from two different agro-climatic zones of Odisha. Transcriptome assembly for both the samples was done using next generation sequencing methodology. The raw data of size 10.8 and 11.8 GB obtained from analysis of two rhizomes S1Z4 and S2Z5 collected from Bhubaneswar and Koraput and are available in NCBI accession number SAMN03761169 and SAMN03761176 respectively. We identified 60,452 and 54,748 transcripts using trinity tool respectively from ginger rhizome of S1Z4 and S2Z5. The transcript length varied from 300 bp to 15,213 bp and 8988 bp and N50 value of 1415 bp and 1334 bp respectively for S1Z4 and S2Z5. To the best of our knowledge, this is the first comparative transcriptome analysis of elite ginger cultivars Suprabha from two different agro-climatic conditions of Odisha, India which will help to understand the effect of agro-climatic conditions on differential expression of secondary metabolites. PMID- 27408810 TI - MicroRNA gene expression signatures in long-surviving malignant pleural mesothelioma patients. AB - Malignant pleural mesothelioma (MPM) is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the world's highest rates of MPM and the incidence is yet to peak. The prognosis for patients with MPM is poor and median survival following diagnosis is 4-18 months. Currently, no or few effective therapies exist for MPM. Trials of targeted agents such as antiangiogenic agents (VEGF, EGFR) or ribonuclease inhibitors (ranpirnase) largely failed to show efficacy in MPM Tsao et al. (2009) [1]. A recent study, however, showed that cisplatin/pemetrexed + bevacizumab (a recombinant humanized monoclonal antibody that inhibit VEGF) treatment has a survival benefit of 2.7 months Zalcman et al. (2016) [2]. It remains to be seen if this targeted therapy will be accepted as a new standard for MPM. Thus the unmet needs of MPM patients remain very pronounced and almost every patient will be confronted with drug resistance and recurrence of disease. We have identified unique gene signatures associated with prolonged survival in mesothelioma patients undergoing radical surgery (EPP, extrapleural pneumonectomy), as well as patients who underwent palliative surgery (pleurectomy/decortication). In addition to data published in Molecular Oncology, 2015;9:715-26 (GSE59180) Kirschner et al. (2015) , we describe here additional data using a system-based approach that support our previous observations. This data provides a resource to further explore microRNA dynamics in MPM. PMID- 27408812 TI - The draft genome sequence and annotation of the desert woodrat Neotoma lepida. AB - We present the de novo draft genome sequence for a vertebrate mammalian herbivore, the desert woodrat (Neotoma lepida). This species is of ecological and evolutionary interest with respect to ingestion, microbial detoxification and hepatic metabolism of toxic plant secondary compounds from the highly toxic creosote bush (Larrea tridentata) and the juniper shrub (Juniperus monosperma). The draft genome sequence and annotation have been deposited at GenBank under the accession LZPO01000000. PMID- 27408811 TI - Genome-wide identification and characterization of R2R3MYB family in Rosaceae. AB - Transcription factors R2R3MYB family have been associated with the control of secondary metabolites, development of structures, cold tolerance and response to biotic and abiotic stress, among others. In recent years, genomes of Rosaceae botanical family are available. Although this information has been used to study the karyotype evolution of these species from an ancestral genome, there are no studies that treat the evolution and diversity of gene families present in these species or in the botanical family. Here we present the first comparative study of the R2R3MYB subfamily of transcription factors in three species of Rosaceae family (Malus domestica, Prunus persica and Fragaria vesca). We described 186, 98 and 86 non-redundant gene models for apple, peach and strawberry, respectively. In this research, we analyzed the intron-exon structure and genomic distribution of R2R3MYB families mentioned above. The phylogenetic comparisons revealed putative functions of some R2R3MYB transcription factors. This analysis found 44 functional subgroups, seven of which were unique for Rosaceae. In addition, our results showed a highly collinearity among some genes revealing the existence of conserved gene models between the three species studied. Although some gene models in these species have been validated under several approaches, more research in the Rosaceae family is necessary to determine gene expression patterns in specific tissues and development stages to facilitate understanding of the regulatory and biochemical mechanism in this botanical family. PMID- 27408813 TI - Transcriptomic analyses of Hand2 transgenic embryos. AB - In this article, we further provide the data generated for the previously published research article "Specification of jaw identity by the Hand2 transcription factor." To better understand the downstream genes of the basic helix-loop-helix transcription factor Hand2, we generated double-transgenic mice (Hand2 (NC) ) by intercrossing CAG-floxed CAT-Hand2 mice with Wnt1-Cre mice for conditional activation of Hand2 expression in the neural crest. Altered expression of Hand2 induces transformation of the upper jaw to the lower jaw in Hand2 (NC) mutant mice. This data article provides Tables detailing the differentially expressed genes between wild-type and Hand2 (NC) mutant embryos. The raw array data of our transcriptomes as generated using Affymetrix microarrays are available on the NCBI Gene Expression Omnibus (GEO) browser (Reference number GSE75805). PMID- 27408814 TI - Metagenomic analysis of microbial community of an Amazonian geothermal spring in Peru. AB - Aguas Calientes (AC) is an isolated geothermal spring located deep into the Amazon rainforest (7 degrees 21'12" S, 75 degrees 00'54" W) of Peru. This geothermal spring is slightly acidic (pH 5.0-7.0) in nature, with temperatures varying from 45 to 90 degrees C and continually fed by plant litter, resulting in a relatively high degree of total organic content (TOC). Pooled water sample was analyzed at 16S rRNA V3-V4 hypervariable region by amplicon metagenome sequencing on Illumina HiSeq platform. A total of 2,976,534 paired ends reads were generated which were assigned into 5434 numbers of OTUs. All the resulting 16S rRNA fragments were then classified into 58 bacterial phyla and 2 archaeal phyla. Proteobacteria (88.06%) was found to be the highest represented phyla followed by Thermi (6.43%), Firmicutes (3.41%) and Aquificae (1.10%), respectively. Crenarchaeota and Euryarchaeota were the only 2 archaeal phyla detected in this study with low abundance. Metagenomic sequences were deposited to SRA database which is available at NCBI with accession number SRX1809286. Functional categorization of the assigned OTUs was performed using PICRUSt tool. In COG analysis "Amino acid transport and metabolism" (8.5%) was found to be the highest represented category whereas among predicted KEGG pathways "Metabolism" (50.6%) was the most abundant. This is the first report of a high resolution microbial phylogenetic profile of an Amazonian hot spring. PMID- 27408816 TI - Microarray analysis of microRNA expression in mouse fetus at 13.5 and 14.5 days post-coitum in ear and back skin tissues. AB - There is no information regarding the role of microRNAs in the development of the external ear in mammals. The purpose of this study was to determine the stage specific expression of microRNA during external ear development in mice under normal conditions. GeneChip miRNA 3.0 arrays by Affymetrix were used to obtain miRNA expression profiles from mice fetal pinnae and back skin tissues at 13.5 days-post-coitum (dpc) and 14.5 dpc. Biological triplicates for each tissue were analyzed; one litter represents one biological replica, each litter had 16 fetuses on average. The results were analyzed with Affymetrix's Transcriptome Analysis Console software to identify differentially expressed miRNAs. The inquiry showed significant differential expression of 25 miRNAs at 13.5 dpc and 31 at 14.5 dpc, some of these miRNAs were predicted to target genes implicated in external ear development. One example is mmu-miR-10a whose low expression in pinnae is known to impact ear development by modulating Hoxa1 mRNA levels Garzon et al. (2006), Gavalas et al. (1998) [1], [2]. Other findings like the upregulation of mmu-miR-200c and mmu-miR-205 in the pinnae tissues of healthy mice are in agreement with what has been reported in human patients with microtia, in which down regulation of both miRNAs has been found Li et al. (2013) [3]. This study uncovered a spatiotemporal pattern of miRNA expression in the external ear, which results from continuous transcriptional changes during normal development of body structures. All microarray data are available at the Gene Expression Omnibus (GEO) at NCBI under accession number GSE64945. PMID- 27408815 TI - Transcriptome profiling of TDC cluster deletion mutant of Enterococcus faecalis V583. AB - The species Enterococcus faecalis is able to catabolise the amino acid tyrosine into the biogenic amine tyramine by the tyrosine decarboxilase (TDC) pathway Ladero et al. (2012) [1]. The TDC cluster comprises four genes: tyrS, an aminoacyl-tRNA synthetase-like gene; tdcA, which encodes the tyrosine decarboxylase; tyrP, a tyrosine/tyramine exchanger gene and nhaC-2, which encodes an Na(+)/H(+) antiporter and whose role in the tyramine biosynthesis remains unknown [2]. In E. faecalis V583 the last three genes are co-transcribed as a single polycistronic mRNA forming the catabolic operon, while tyrS is transcribed independently of the catabolic genes as a monocistronic mRNA [2]. The catabolic operon is transcriptionally induced by tyrosine and acidic pH. On the opposite, the tyrS expression is repressed by tyrosine concentrations [2]. In this work we report the transcriptional profiling of the TDC cluster deletion mutant (E. faecalis V583 DeltaTDC) [2] compared to the wild-type strain, both grown in M17 medium supplemented with tyrosine. The transcriptional profile data of TDC cluster-regulated genes were deposited in the Gene Expression Omnibus (GEO) database under accession no. GSE77864. PMID- 27408817 TI - De Novo transcriptome assembly of Zingiber officinale cv. Suruchi of Odisha. AB - Zingiber officinale Rosc., known as ginger, is an Asian crop, popularly used in every household kitchen and commercially used in bakery, beverage, food and pharmaceutical industries. The present study deals with de novo transcriptome assembly of an elite ginger cultivar Suruchi by next generation sequencing methodology. From the analysis 10.9 GB raw data was obtained which can be available in NCBI accession number SAMN03761185. We identified 41,969 transcripts using Trinity RNA-Seq from ginger rhizome of Suruchi variety from Odisha. The transcript length varied from 300 bp to 8404 bp with a total length of 3,96,40,526 bp and N50 of 1251 bp. To the best of our knowledge, this is the first transcriptome data of an elite ginger cultivar Suruchi released for Odisha state of India which will help molecular biologists to develop genetic markers for identification of cultivars. PMID- 27408818 TI - Functional profiling of cyanobacterial genomes and its role in ecological adaptations. AB - With the availability of complete genome sequences of many cyanobacterial species, it is becoming feasible to study the broad prospective of the environmental adaptation and the overall changes at transcriptional and translational level in these organisms. In the evolutionary phase, niche-specific competitive forces have resulted in specific features of the cyanobacterial genomes. In this study, functional composition of the 84 different cyanobacterial genomes and their adaptations to different environments was examined by identifying the genomic composition for specific cellular processes, which reflect their genomic functional profile and ecological adaptation. It was identified that among cyanobacterial genomes, metabolic genes have major share over other categories and differentiation of genomic functional profile was observed for the species inhabiting different habitats. The cyanobacteria of freshwater and other habitats accumulate large number of poorly characterized genes. Strain specific functions were also reported in many cyanobacterial members, of which an important feature was the occurrence of phage-related sequences. From this study, it can be speculated that habitat is one of the major factors in giving the shape of functional composition of cyanobacterial genomes towards their ecological adaptations. PMID- 27408819 TI - Clinical response to eliglustat in treatment-naive patients with Gaucher disease type 1: Post-hoc comparison to imiglucerase-treated patients enrolled in the International Collaborative Gaucher Group Gaucher Registry. AB - Eliglustat is a recently approved oral therapy in the United States and Europe for adults with Gaucher disease type 1 who are CYP2D6 extensive, intermediate, or poor metabolizers (> 90% of patients) that has been shown to decrease spleen and liver volume and increase hemoglobin concentrations and platelet counts in untreated adults with Gaucher disease type 1 and maintain these parameters in patients previously stabilized on enzyme replacement therapy. In a post-hoc analysis, we compared the results of eliglustat treatment in treatment-naive patients in two clinical studies with the results of imiglucerase treatment among a cohort of treatment-naive patients with comparable baseline hematologic and visceral parameters in the International Collaborative Gaucher Group Gaucher Registry. Organ volumes and hematologic parameters improved from baseline in both treatment groups, with a time course and degree of improvement in eliglustat treated patients similar to imiglucerase-treated patients. PMID- 27408820 TI - Creatine transporter deficiency: Novel mutations and functional studies. AB - X-linked cerebral creatine deficiency (MIM 300036) is caused by deficiency of the creatine transporter encoded by the SLC6A8 gene. Here we report three patients with this condition from Israel. These unrelated patients were evaluated for global developmental delays and language apraxia. Borderline microcephaly was noted in one of them. Diagnosis was prompted by brain magnetic resonance imaging and spectroscopy which revealed normal white matter distribution, but absence of the creatine peak in all three patients. Biochemical testing indicated normal plasma levels of creatine and guanidinoacetate, but an increased urine creatine/creatinine ratio. The diagnosis was confirmed by demonstrating absent ([14])C-creatine transport in fibroblasts. Molecular studies indicated that the first patient is hemizygous for a single nucleotide change substituting a single amino acid (c.619 C > T, p.R207W). Expression studies in HeLa cells confirmed the causative role of the R207W substitution. The second patient had a three base pair deletion in the SLC6A8 gene (c.1222_1224delTTC, p.F408del) as well as a single base change (c.1254 + 1G > A) at a splicing site in the intron-exon junction of exon 8, the latter occurring de novo. The third patient, had a three base pair deletion (c.1006_1008delAAC, p.N336del) previously reported in other patients with creatine transporter deficiency. These three patients are the first reported cases of creatine transporter deficiency in Israel. PMID- 27408821 TI - Hypothyroidism in late-onset Pompe disease. AB - PURPOSE: In Pompe disease, a deficiency of acid alpha-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. METHODS: Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. RESULTS: The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p < 0.001 compared with the general UMMC adult population). CONCLUSIONS: Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease. PMID- 27408822 TI - Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation. AB - Leigh syndrome is a mitochondrial disease caused by mutations in different genes, including ATP6A for which no known therapy is available. We report a case of adult-onset Leigh syndrome with response to immunotherapy. A twenty year-old woman with baseline learning difficulties was admitted with progressive behavioral changes, diplopia, headaches, bladder incontinence, and incoordination. Brain MRI and PET scan showed T2 hyperintensity and increased uptake in bilateral basal ganglia, respectively. Autoimmune encephalitis was suspected and she received plasmapheresis with clinical improvement. She was readmitted 4 weeks later with dysphagia and aspiration pneumonia. Plasmapheresis was repeated with resolution of her symptoms. Given the multisystem involvement and suggestive MRI changes, genetic testing was done, revealing a homoplasmic T9176C ATPase 6 gene mtDNA mutation. Monthly IVIG provided clinical improvement with worsening when infusions were delayed. Leigh syndrome secondary to mtDNA T9176C mutations could have an autoimmune mechanism that responds to immunotherapy. PMID- 27408824 TI - Considerations about the in situ derivatization and fractionation of EFA and NEFA in biological and food samples. AB - Despite their important role in tissues, fluids and foods, the analysis of non esterified fatty acids (NEFA) as methyl esters (NEFAME) is performed using expensive, cumbersome and time-consuming procedures that needs of isolation, fractionation and derivatization steps. However, Yi et al. [1] proposed a promising in situ, single-step procedure to analyze esterified fatty acids (EFA) and NEFA from a same sample on the basis that acylglycerols and free fatty acids can be derivatized using specific reactions. However, according to the data presented in this research work, some modifications need to be performed to increase the reliability of the method:*Increment of the transesterification performance by adding hexane to the reaction mixture, decreasing the time for the derivatization of acylglycerols from 10 min to 3-4 min and stopping the reaction with sulfuric acid.*Avoid cross-contamination of the NEFAME extract by adding 500 MUL of water after collection of EFA methyl esters (EFAME).*Samples are spiked with three internal standards: a triacylglycerol (to calculate the concentration of EFA), a free fatty acid (to calculate NEFA) and a FAME (to control isolation of FAME and cross-contamination). PMID- 27408823 TI - Polymorphisms of apolipoprotein E and aneurysmal subarachnoid haemorrhage: A meta analysis. AB - Subarachnoid haemorrhage (SAH) is characterised by bleeding in the subarachnoid space in the brain. There are various polymorphisms in genes which are associated with this disease. We performed a systematic meta- analysis to investigate the relationship of APOE polymorphism on aSAH. A comprehensive literature search was done in the Pubmed database, Science Direct, Cochrane library and Google Scholar. The OR and 95% CI were evaluated for the gene and aSAH association using fixed and random effect models. Publication bias was assessed using Begg's funnel plot and Egger's regression test. All statistical evaluations were done using the software Review Manager 5.0 and Comprehensive Meta Analysis v2.2.023. A total of 9 studies were assessed on APOE polymorphism (1100 Cases, 2732 Control). Meta analysis results showed significant association in epsilon2/ epsilon2 versus epsilon3/epsilon3, epsilon2 versus epsilon3 genetic models and epsilon2 allele frequency. In subgroup analysis statistically significant association was observed in Asians in the genetic models epsilon2/ epsilon2 versus epsilon3/epsilon3, epsilon2/epsilon3 versus epsilon3/epsilon3, epsilon2 versus epsilon3 and also in epsilon2 allele frequency. However, in Caucasian population only epsilon2/epsilon2 versus epsilon3/epsilon3 genetic model showed significant association between APOE and risk of aSAH. In this meta-analysis study, the epsilon2/epsilon2 genotype is associated with increased risk of aSAH. PMID- 27408825 TI - Determination of dimensions of exfoliating materials in aqueous suspensions. AB - A method for measurement of dimensions of platy particles of exfoliating, or delaminating, materials, such as clays, in aqueous suspensions in situ is proposed. Equivalent spherical diameter (esd), measured by many common methods, depends more on the major (lateral) dimension of a particle, while it is less sensitive to changes of the particle thickness. Addition of the second method, results of which are a function of the particle diameter and thickness too, would provide more accurate determination of the particle dimensions. Previously, a combination of low-temperature nitrogen adsorption (BET) and dynamic light scattering (DLS) methods for determination of specific surface area of dry powder of platy particles and their esd in suspension was suggested. While such combination was suitable for measurement of particle size for non-exfoliating materials, it gave incorrect results for exfoliating materials, which dramatically change their surface area when dispersed in liquid. We modify this method by substituting BET method with NMR relaxometry, which allows to measure wetted surface area of the dispersed material directly in suspension. The advantages of this method are:*More accurate determination of diameter and thickness of platy, particularly exfoliating, materials directly in suspension.*Possibility of routine monitoring of particle size changes during the dispersing process. PMID- 27408826 TI - Aqueous based reflux method for green synthesis of nanostructures: Application in CZTS synthesis. AB - The aqueous based reflux method useful for the green synthesis of nanostructures is described in detail. In this method, the parameters: the order of addition of precursors, the time of the reflux and the cooling rate should be optimized in order to obtain the desired phase and morphology of the nanostructures. The application of this method is discussed with reference to the synthesis of CZTS nanoparticles which have great potential as an absorber material in the photovoltaic devices. The highlights of this method are:*Simple.*Low cost.*Aqueous based. PMID- 27408827 TI - The optimal algorithm for Multi-source RS image fusion. AB - In order to solve the issue which the fusion rules cannot be self-adaptively adjusted by using available fusion methods according to the subsequent processing requirements of Remote Sensing (RS) image, this paper puts forward GSDA (genetic iterative self-organizing data analysis algorithm) by integrating the merit of genetic arithmetic together with the advantage of iterative self-organizing data analysis algorithm for multi-source RS image fusion. The proposed algorithm considers the wavelet transform of the translation invariance as the model operator, also regards the contrast pyramid conversion as the observed operator. The algorithm then designs the objective function by taking use of the weighted sum of evaluation indices, and optimizes the objective function by employing GSDA so as to get a higher resolution of RS image. As discussed above, the bullet points of the text are summarized as follows.*The contribution proposes the iterative self-organizing data analysis algorithm for multi-source RS image fusion.*This article presents GSDA algorithm for the self-adaptively adjustment of the fusion rules.*This text comes up with the model operator and the observed operator as the fusion scheme of RS image based on GSDA. The proposed algorithm opens up a novel algorithmic pathway for multi-source RS image fusion by means of GSDA. PMID- 27408828 TI - Determination of Sb(III) and Sb(V) by HPLC-Online isotopic dilution-ICP MS. AB - This work provides a method with application of valid techniques to extract and determinate inorganic species of antimony (Sb) for water. The procedure involves*the simultaneous accumulation of Sb(III) and Sb(V) on passive samplers like Diffusive Gradient in Thin Films (DGT) with iron (Fe) oxide gel, eliminating the risk of speciation changes due to transport and storage;*application of less concentrated acid (50 mM Na2EDTA) for elution and preservation of Sb species from DGT resin;*subsequent analytical determination of inorganic species with High Performance Liquid Chromatography-Isotopic Dilution-Inductively Coupled Plasma Mass Spectrometer (HPLC-ID-ICP MS) based on determination of the isotope ratio ((123)Sb/(121)Sb) of isotopes in the samples after spiking with 123Sb enriched standard solution, reducing the effect of signal drift and matrix effect on the final value. PMID- 27408829 TI - AZDAST the new horizon in antimicrobial synergism detection. AB - The attempts via introducing many methods have been conducted to select the best antibiotic combination in the treatment of seriously ill patients. Operational or interpretational complexity or time-consuming along with sufficient accuracy led to postpone routine clinical use of these tests until today, despite the urgent need for them. By this study and proposed method, selection of the best double antibiotic synergistic combination against resistant pathogen is simply same as Kirby-Bauer antibiotic susceptibility test. It seems, precise and reliable results (very low coefficient of variation) will be introduced it as a routine accurate diagnostic doubled antimicrobial synergism test.*The objective of this study was to introduce a novel method in antibiotic interaction detection.*It demonstrates high sensitivity and accuracy.*Easy implementation by routine microbiology labs materials and equipment and so easy stand-alone interpretation seems to make it friendly test be able to replacing the previous methods. PMID- 27408830 TI - Determining wave direction using curvature parameters. AB - The curvature of the sea wave was tested as a parameter for estimating wave direction in the search for better results in estimates of wave direction in shallow waters, where waves of different sizes, frequencies and directions intersect and it is difficult to characterize. We used numerical simulations of the sea surface to determine wave direction calculated from the curvature of the waves. Using 1000 numerical simulations, the statistical variability of the wave direction was determined. The results showed good performance by the curvature parameter for estimating wave direction. Accuracy in the estimates was improved by including wave slope parameters in addition to curvature. The results indicate that the curvature is a promising technique to estimate wave directions.*In this study, the accuracy and precision of curvature parameters to measure wave direction are analyzed using a model simulation that generates 1000 wave records with directional resolution.*The model allows the simultaneous simulation of time series wave properties such as sea surface elevation, slope and curvature and they were used to analyze the variability of estimated directions.*The simultaneous acquisition of slope and curvature parameters can contribute to estimates wave direction, thus increasing accuracy and precision of results. PMID- 27408831 TI - Development of methodologies for virus detection in soybean and wheat seeds. AB - Seeds that contain large amounts of oil, starch, fibers and phenols are the most difficult tissues for RNA extraction. Currently, there are some reports of virus detection in seeds using commercial kits for RNA extraction. However, individual seeds were used, which may not be always suitable for analyses that deal with large amounts of seeds. Sangha [1] described a simple, quick and efficient protocol for RNA extraction and downstream applications in a group of seeds of jatropha (Jatropha curcas), mustard (Brassica sp.) and rice (Oryza sativa). We tested this protocol for soybean (Glycine max), maize (Zea mays), wheat (Triticum aestivum) and triticale (*Triticosecale) seeds and further reverse transcription PCR (RT-PCR)/quantitative real-time PCR (qPCR) in order to have a faster and more practical method for virus detection from seeds than the traditional scheme of seed planting and subsequent Elisa/RT-PCR from leaves. The essential points in the method are:*Some modifications in the protocol [1] were done in order to increase performance: Wheat and triticale seeds are incubated with water prior to maceration. An amount of 1.2 g of dry soybean seeds is used to maceration.*RT-PCR is used for detection of Wheat streak mosaic virus from wheat seeds and RT-qPCR for detection of Soybean mosaic virus from soybean seeds.*The method may be tested for other viruses, however, pre-validation will be needed. PMID- 27408832 TI - Voxelization algorithms for geospatial applications: Computational methods for voxelating spatial datasets of 3D city models containing 3D surface, curve and point data models. AB - Voxel representations have been used for years in scientific computation and medical imaging. The main focus of our research is to provide easy access to methods for making large-scale voxel models of built environment for environmental modelling studies while ensuring they are spatially correct, meaning they correctly represent topological and semantic relations among objects. In this article, we present algorithms that generate voxels (volumetric pixels) out of point cloud, curve, or surface objects. The algorithms for voxelization of surfaces and curves are a customization of the topological voxelization approach [1]; we additionally provide an extension of this method for voxelization of point clouds. The developed software has the following advantages:*It provides easy management of connectivity levels in the resulting voxels.*It is not dependant on any external library except for primitive types and constructs; therefore, it is easy to integrate them in any application.*One of the algorithms is implemented in C++ and C for platform independence and efficiency. PMID- 27408834 TI - Asia Oceania Journal of Nuclear Medicine & Biology; A big step forward to advance scientific publication & cooperation in the region. PMID- 27408833 TI - An LC-MS/MS method for the determination of budesonide and 16alpha hydroxyprednisolone in dog plasma. AB - Although budesonide is frequently used in veterinary medicine for the treatment of canine respiratory and bowel inflammatory diseases, knowledge is lacking regarding its kinetics in this species. We developed and validated a liquid chromatography-tandem mass spectrometry method for the determination of budesonide and its metabolite 16alpha-hydroxyprednisolone in dog plasma. The analytes were extracted by solid phase extraction and analysis was performed by high performance liquid chromatography-tandem mass spectrometry, with positive electrospray ionization.*This method allows budesonide and one of its main metabolites to be simultaneously quantified in dog plasma at fairly low concentrations.*The proposed protocol is very easy and fast to execute, without compromising analytical performances.*A small amount (0.5 mL) of plasma is required, making this approach suitable for pharmacokinetic studies also in small sized dogs. PMID- 27408835 TI - History and Perspectives of AOFNMB. PMID- 27408836 TI - Both F-18 FDG-avidity and Malignant Shape of Cervical Lymph Nodes on PET/CT after Total Thyroidectomy Predict Resistance to High-dose I-131 Therapy in Patients with Papillary Thyroid Cancer. AB - OBJECTIVE: Resistance of metastatic lymph nodes (LNs) to high dose I-131 therapy is associated with high morbidity in patients with differentiated thyroid cancer. We evaluated the role of F-18 FDG PET/CT in the prediction of resistance to high dose I-131 therapy in patients with papillary thyroid cancer. METHODS: The subjects were 307 patients who underwent total or near total thyroidectomy followed by high dose (5.55-6.66 GBq) I-131 therapy. We divided the patients into three subgroups by visual assessment of regional LNs: FDG-avid LNs with a malignant shape on CT (PET/CT-positive group), FDG-avid LNs with a benign shape on CT (PET/CT-intermediate group) and no FDG-avid lesion (PET/CT-negative group). We measured the maximum SUV (SUVmax) of FDG-avid LNs in each patient. The presence or absence of focal increased uptake of I-131 was evaluated by whole body scan (WBS), and was denoted as WBS-positive group or WBS-negative group, respectively. Resistance to therapy was defined as presence of thyroglobulin (Tg) in serum (Tg >=1.0 ng/ml) 3-6 months after I-131 therapy. Univariate and multivariate analyses were performed to determine the relationship between resistance to I-131 therapy and various clinico-pathologic variables. RESULTS: PET/CT-positive, intermediate, and negative groups included 20 (6.5%), 44 (14.3%) and 243 (79.2%) patients, respectively. The mean SUVmax was significantly higher in the PET/CT-positive group than that of the PET/CT-intermediate group (4.6 vs. 2.7, P <0.001). Univariate analysis revealed that the PET/CT-positive group (P <0.001), T2-4 stage (P <0.001), N1b stage (P = 0.001), lower dose (5.55 GBq) of I 131 (P <0.001), and the WBS-positive group (P = 0.029) were associated with resistance to therapy. In multivariate analysis, the PET/CT-positive group, lower dose of I-131, N1b stage, and T2-4 stage remained significant with odds ratios of 10.07 (P <0.001), 3.82 (P <0.001), 3.58 (P = 0.001), and 2.53 (P = 0.009), respectively. CONCLUSION: FDG-avidity and malignant shape of cervical LNs on pre therapy FDG PET/CT were a strong risk factors predicting resistance to high dose I-131 therapy. A lower dose of administered I-131 (5.55 GBq) and more extensive tumors (T2-4 and N1b) were also associated with resistance to high dose I-131 therapy. PMID- 27408837 TI - Clinical value and severity of myocardial perfusion defects in asymptomatic diabetic patients with negative or weakly positive exercise treadmill test. AB - OBJECTIVE: Although coronary artery disease (CAD) is the leading cause of death in type 2 diabetic patients, it is frequently asymptomatic. Myocardial perfusion imaging (MPI) is reported to show ischemia in a significant number of asymptomatic diabetic patients. We studied the prevalence and severity of myocardial perfusion defects in asymptomatic diabetic patients and its clinical impact. METHODS AND PATIENTS: One hundred thirty consecutive asymptomatic patients, aged 35-65 years with type 2 diabetes mellitus and with no history of CAD and no cardiac symptoms were recruited in the study. Echocardiography, electrocardiography (ECG), routine laboratory tests and exercise treadmill test (ETT) were performed and patients with weakly positive or negative ETT underwent Dipyridamole MPI. Patients with positive ETT were referred to coronary angiography. Patients were followed for at least 17 months (mean 21.7 months) and any cardiac event was recorded. RESULTS: We studied 81 female and 49 male patients with mean age of 51.8 years. Negative, weakly positive and positive ETT result was noted in 74.3%, 15% and 10.7% respectively. 75% of patients with positive ETT had coronary artery disease in angiography. Gated myocardial perfusion SPECT was done in 106 patients. MPI showed reversible defect in 26.9% of the patients with a mean summed stress score of 3.3+/-1.8. Follow up completed in 112 patients and only one patient with abnormal MPI underwent coronary angiography followed by PTCA. No cardiac death, MI, UA or hospital admission occurred among our patients during follow up (17-26 months). Mean stress end diastolic volume (EDV) was significantly higher in patients with reversible defect compared to patients without reversible defect based on MPI findings (62.0+/-31.6 Vs 48.5+/-18.4 ml, P=0.04). Blood glucose and HbA1c were significantly higher in patients with ischemia compared to patients without ischemia (P<0.05). Meanwhile the ratio of TG to HDL was 6.06+/-3.2 in ischemic patients compared to 4.8+/-2.3 in normal subjects (P=0.03). CONCLUSION: Reversible defects are commonly seen in myocardial perfusion SPECT in asymptomatic diabetic patients and are mild in severity and not associated with adverse cardiac events. Routine approach for detection of CAD beginning with ETT seems to be appropriate in these patients. PMID- 27408838 TI - Thyroid hormone replacement one day before (131)I therapy in patients with well differentiated thyroid cancer. AB - OBJECTIVE: The current study aimed to determine the efficacy of radioiodine-131 ((131)I) ablation therapy with thyroid hormone replacement one day before (131)I administration in patients with well-differentiated thyroid cancer (DTC). METHODS: This retrospective study included 29 patients who underwent (131)I therapies twice for DTC during 6-12 months. Since all the patients obviously had residual lesions by their serum thyroglobulin levels or their scintigrams at the first therapies, they underwent the second (131)I therapies without diagnostic scintigraphy after the first therapies. After confirming the sufficient elevation of TSH concentration, thyroid hormone replacement was resumed one day before (131)I administration (3.7-7.4GBq). The ablation rate of thyroid remnant at the first (131)I therapy was evaluated by comparing (131)I post-therapeutic images of the two treatments. RESULTS: Three patients were administrated thyroid hormone after (131)I therapy because of insufficient TSH concentration under thyroid hormone withdrawal. In the remaining 26 patients, 41 thyroid remnant accumulations were detected in all 26 patients at the first (131)I therapy. Based on the second (131)I post-therapeutic images, successful ablation was confirmed in 24 of 26 patients (92.3%) and 38 of 41 sites (92.7%), which was comparable with historically reported ablation rates. CONCLUSION: Thyroid hormone replacement one day before (131)I therapy could provide a sufficiently high ablation rate in patients with DTC. PMID- 27408839 TI - Treatment efficacy of (153)Sm-EDTMP for painful bone metastasis. AB - INTRODUCTION: Involvement of the skeleton can cause an excruciating pain in two thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. METHODS: 28 patients (14 males and 14 females) aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. RESULTS: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean+/-SD=15.22+/-7.8). 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%). The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. CONCLUSION: Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved. PMID- 27408840 TI - Synthesis, Radioiodination and Biodistribution Evaluation of 5-(2-amimo-4-styryl pyrimidine-4-yl)-4-methoxybenzofuran-6-ol. AB - This study describes the organic synthesis of 5-(2-amimo-4-styryl pyrimidine-4 yl)-4-methoxy benzofuran-6-ol (SPBF) as an example of a benzofuran derivative used as a new series of amyloid imaging agents. These benzofuran derivatives may be useful amyloid imaging agents for detecting B-amyloid plagues in the brain of Alzheimer's disease. The precursor is 1-[6-hydroxy-4-methoxybenzofuran-5-yl] phenyl butadiene ketone, which react with guanidine hydrochloride. The purification process was done via crystallization using solvent ethanol. The overall yield was 75% and the structure of the synthesized compound was confirmed by correct analytical and spectral data. Also, The synthesized compound was labeled with radioactive iodine -125 via electrophilic substitution reaction, in the presence of iodogen as an oxidizing agent, the labeling process was carried out at 95 degrees C for 20min. The radiochemical yield was determined by using a thin layer chromatography and the yield was equal to 80%. Preliminary an in-vivo study examined normal mice after intravenous injection through the tail vein and the data showed the labeling compound was quickly cleared from most body organs. The radioiodinated compound showed high brain uptake. The results of this study suggest that radioiodinated (SPBF) may be useful as a brain imaging agents. PMID- 27408841 TI - Evaluation of Cardiac Mitochondrial Function by a Nuclear Imaging Technique using Technetium-99m-MIBI Uptake Kinetics. AB - Mitochondria play an important role in energy production for the cell. The proper function of a myocardial cell largely depends on the functional capacity of the mitochondria. Therefore it is necessary to establish a novel and reliable method for a non-invasive assessment of mitochondrial function and metabolism in humans. Although originally designed for evaluating myocardial perfusion, (99m)Tc-MIBI can be also used to evaluate cardiac mitochondrial function. In a clinical study on ischemic heart disease, reverse redistribution of (99m)Tc-MIBI was evident after direct percutaneous transluminal coronary angioplasty. The presence of increased washout of (99m)Tc-MIBI was associated with the infarct-related artery and preserved left ventricular function. In non-ischemic cardiomyopathy, an increased washout rate of (99m)Tc-MIBI, which correlated inversely with left ventricular ejection fraction, was observed in patients with congestive heart failure. Increased (99m)Tc-MIBI washout was also observed in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and in doxorubicin-induced cardiomyopathy. Noninvasive assessment of cardiac mitochondrial function could be greatly beneficial in monitoring possible cardiotoxic drug use and in the evaluation of cardiac damage in clinical medicine. PMID- 27408842 TI - Ectopic papillary thyroid carcinoma in the mediastinum without any tumoral involvement in the thyroid gland. A Case report. AB - Ectopic thyroid tissue results from abnormal embryologic development and migration of the thyroid gland. True malignant transformation in ectopic thyroid tissue is extremely rare and is always diagnosed after surgical excision of the lesion by pathology examinations. There are well-documented cases of ectopic thyroid cancer while primary tumoral lesion occurs in the orthotopic thyroid, but only rare cases of ectopic PTC without any evidence of occult thyroid cancer in the orthotopic thyroid or cervical lymph nodes have been reported. We report on a 39 year old woman who was operated for a mediastinal mass. The initial diagnosis was a malignant thymic lesion, which was later confirmed to be a papillary thyroid carcinoma. Consequently, total thyroidectomy was performed and pathology report showed normal thyroid tissue with no evidence of any neoplastic involvement. Until now, only one similar case has been reported. PMID- 27408843 TI - The Asian Nuclear Medicine Board (ANMB); Why Do We Need It? PMID- 27408844 TI - (99m)Tc-MIBI Washout Rate to Evaluate the Effects of Steroid Therapy in Cardiac Sarcoidosis. AB - OBJECTIVE: We sought to determine the usefulness of the (99m)Tc-MIBI (MIBI) washout rate for the evaluation of steroid therapy in cardiac sarcoidosis (CS). METHODS: Eleven CS patients underwent MIBI myocardial SPECT both before and 6 months after initiating steroid therapy. The washout rate (WOR) of MIBI was calculated using early and delayed polar map images. The washout score (WOS) of MIBI was derived from the difference between the early and delayed total defect scores (TDS). RESULTS: Serum ACE and BNP exhibited significant improvement after the therapy (p = 0.004, p = 0.045). In the LV function, EDV and E/A ratio exhibited significant improvement after the therapy (p = 0.041, p = 0.007), while there were no significant differences between before and after therapy in EF or ESV. Early and delayed TDS showed no significant differences between before and after the therapy. In contrast, WOR differed significantly (p <. 0001), while WOS did not differ significantly between before and after the therapy. CONCLUSION: The washout rate of MIBI is suitable for assessment of cardiac function in CS with steroid therapy, being especially better than the washout score of MIBI for assessment of disease activity of mild myocardial damage in CS with steroid therapy. PMID- 27408845 TI - Translation of Methodology Used In Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction. AB - INTRODUCTION: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly uses rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to intervention. METHODS: Eighteen sheep were enrolled in a pilot study to evaluate [(99m)Tc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement was measured using Kappa (kappa). Power determined the sample sizes needed to show statistically significant changes due to intervention. RESULTS: Ten sheep completed the full protocol. Data processed was performed with pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15%-35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (K=0.89). Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion. CONCLUSION: This study demonstrates the suitability of large animal models for imaging with standard MPI protocols and its feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair. PMID- 27408846 TI - Is (99m)Tc-MIBI scintigraphy a predictor of response to pre-operative neoadjuvant chemotherapy in Osteosarcoma? AB - OBJECTIVES: Multidrug resistance (MDR), which may be due to the over expression of P-glycoprotein (Pgp) and/or MRP, is a major problem in neoadjuvant chemotherapy of osteosarcoma. The aim of this study was to investigate the role of Tc-99m MIBI scan for predicting the response to pre-operative chemotherapy. METHODS: Twenty-five patients (12 males and 13 females, aged between 8 and 52y) with osteosarcoma were studied. Before the chemotherapy, planar (99m)Tc-MIBI anterior and posterior images were obtained 10-min [tumor-to-background ratio: (T1/B1)10min] and 3-hr after tracer injection. After completion of chemotherapy, again (99m)Tc-MIBI scan was performed at 10-min after tracer injection. In addition to calculation of decay corrected tumor to background (T/B) ratios, using the 10-min and 3-hr images of the pre-chemotherapy scintigraphy, percent wash-out rate (WR%) of (99m)Tc-MIBI was calculated. Using the 10-min images of the pre- and post-chemotherapy scans, the percent reduction in uptake at the tumor site after treatment (Red%) was also calculated. Then after surgical resection, tumor response was assessed by percentage of necrosis. RESULTS: All patients showed significant (99m)Tc-MIBI uptake in early images. Only 9 patients showed good response to chemotherapy (necrosis>=90%) while 16 patients were considered as non-responder (necrosis<90%). There was no statistical significant difference between non-responders and responders in (T1/B1)10min.There was a significant negative correlation between WR% and percentage of necrosis (P=0.001). On the other hand, there was a significant correlation between Red% and percentage of necrosis (P<0.001).There was also statistical significant difference in WR% and Red% between non-responders and responders (both P< 0.001). CONCLUSION: Washout rate of (99m)Tc-MIBI in pre-chemotherapy scintigraphy as well as Red% using pre- and post-chemotherapy MIBI scintigraphy are useful methods for predicting response to neoadjuvant chemotherapy. PMID- 27408847 TI - Differential impact of multi-focus fan beam collimation with L-mode and conventional systems on the accuracy of myocardial perfusion imaging: Quantitative evaluation using phantoms. AB - OBJECTIVES: A novel IQ-SPECTTM method has become widely used in clinical studies. The present study compares the quality of myocardial perfusion images (MPI) acquired using the IQ-SPECTTM (IQ-mode), conventional (180 degrees apart: C mode) and L-mode (90 degrees apart: L-mode) systems. We assessed spatial resolution, image reproducibility and quantifiability using various physical phantoms. METHODS: SPECT images were acquired using a dual-headed gamma camera with C-mode, L-mode, and IQ-mode acquisition systems from line source, pai and cardiac phantoms containing solutions of (99m)Tc. The line source phantom was placed in the center of the orbit and at +/- 4.0, +/- 8.0, +/- 12.0, +/- 16.0 and +/- 20.0 cm off center. We examined quantifiability using the pai phantom comprising six chambers containing 0.0, 0.016, 0.03, 0.045, 0.062, and 0.074 MBq/mL of 99m-Tc and cross-calibrating the SPECT counts. Image resolution and reproducibility were quantified as myocardial wall thickness (MWT) and %uptake using polar maps. RESULTS: The full width at half maximum (FWHM) of the IQ-mode in the center was increased by 11% as compared with C-mode, and FWHM in the periphery was increased 41% compared with FWHM at the center. Calibrated SPECT counts were essentially the same when quantified using IQ-and C-modes. IQ-SPECT images of MWT were significantly improved (P<0.001) over L-mode, and C-mode SPECT imaging with IQ-mode became increasingly inhomogeneous, both visually and quantitatively (C-mode vs. L-mode, ns; C-mode vs. IQ-mode, P<0.05). CONCLUSION: Myocardial perfusion images acquired by IQ-SPECT were comparable to those acquired by conventional and L-mode SPECT, but with significantly improved resolution and quality. Our results suggest that IQ-SPECT is the optimal technology for myocardial perfusion SPECT imaging. PMID- 27408848 TI - Impact of PET - CT motion correction in minimizing the gross tumor volume in non small cell lung cancer. AB - OBJECTIVES: To investigate the impact of respiratory motion on localization, and quantification of lung lesions for the Gross Tumor Volume utilizing a fully automated Auto3Dreg program and dynamic NURBS-based cardiac-torso digitized phantom (NCAT). METHODS: Respiratory motion may result in more than 30% underestimation of the SUV values of lung, liver and kidney tumor lesions. The motion correction technique adopted in this study was an image-based motion correction approach using, a voxel-intensity-based and a multi-resolution multi optimization (MRMO) algorithm. The NCAT phantom was used to generate CT attenuation maps and activity distribution volumes for the lung regions. All the generated frames were co-registered to a reference frame using a time efficient scheme. Quantitative assessment including Region of Interest (ROI), image fidelity and image correlation techniques, as well as semi-quantitative line profile analysis and qualitatively overlaying non-motion and motion corrected image frames were performed. RESULTS: The largest motion was observed in the Z direction. The greatest translation was for the frame 3, end inspiration, and the smallest for the frame 5 which was closet frame to the reference frame at 67% expiration. Visual assessment of the lesion sizes, 20-60mm at 3 different locations, apex, mid and base of lung showed noticeable improvement for all the foci and their locations. The maximum improvements for the image fidelity were from 0.395 to 0.930 within the lesion volume of interest. The greatest improvement in activity concentration underestimation was 7.7% below the true activity for the 20 mm lesion in comparison to 34.4% below, prior to correction. The discrepancies in activity underestimation were reduced with increasing the lesion sizes. Overlaying activity distribution on the attenuation map showed improved localization of the PET metabolic information to the anatomical CT images. CONCLUSION: The respiratory motion correction for the lung lesions has led to an improvement in the lesion size, localization and activity quantification with a potential application in reducing the size of the PET GTV for radiotherapy treatment planning applications and hence improving the accuracy of the regime in treatment of lung cancer. PMID- 27408849 TI - Assessment of epidermal growth factor receptor status in glioblastomas. AB - OBJECTIVES: Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline ([(125)I]PYK) is promising for the evaluation of the epidermal growth factor receptor (EGFR) status and prediction of gefitinib treatment of non-small cell lung cancer. EGFR is over-expressed and mutated also in glioblastoma. In the present study, the expressions and mutation of EGFR were tested with [(125)I] PYK in glioblastoma in vitro and in vivo to determine whether this could be used to predict the sensitivity of glioblastoma to gefitinib treatment. METHODS: Glioblastoma cell lines with different expression of EGFR were tested. Growth inhibition of cell lines by gefitinib was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) colorimetric assay. Uptake levels of [(125)I]PYK were evaluated in cell lines in vitro. Tumor targeting of [(125)I]PYK was examined by a biodistribution study and imaging by single photon emission computed tomography (SPECT). RESULTS: High concentrations of gefitinib were needed to suppress EGFR-mediated proliferation. The uptake of [(125)I] PYK in cell lines in vitro was low, and showed no correlation with EGFR expression or mutation status. Biodistribution study and SPECT imaging with [(125)I]PYK for xenografts showed no [(125)I]PYK uptake. CONCLUSION: The results showed prediction of gefitinib effectiveness was difficult in glioblastoma by [(125)I]PYK, which might be due to the complicated expression of EGFR status in glioblastoma. Thus, new tracers for sites downstream of the mutant EGFR should be investigated in further studies. PMID- 27408850 TI - A case of dupable duple duplicity and duplexity. AB - Duplication anomalies are quite common with ureteral duplication anomalies being the most frequent. Despite the relatively frequent incidence of a horseshoe kidney and duplication anomalies in any individual patient, the combination of horseshoe kidney and bilateral ureteric duplication is a very rare entity and very few cases have been reported to date. We present a case of a patient with a novel combination of a horseshoe kidney and multiple rare congenital renal anomalies and their sequelae. PMID- 27408851 TI - Subcutaneous Extravasation of Sr-89: Usefulness of Bremsstrahlung Imaging in Confirming Sr-89 Extravasation and in the Decision Making for the Choice of Treatment Strategies for Local Radiation Injuries Caused by Sr-89 Extravasation. AB - A male patient in his 20s presented at our clinic with pain caused by bone metastases of the primitive neuroectodermal tumor, and Sr-89 was administrated to palliate the pain. After receiving the injection, the patient complained of a slight burning pain at the catheterized area. Slight reddening and small circular swelling (diameter, 0.5 cm) were observed at the catheterized area. Sr-89 extravasation was suspected. To estimate the amount of subcutaneous Sr-89 leakage, bremsstrahlung imaging was immediately performed. We speculated that the skin-absorbed dose from subcutaneous infiltration of Sr-89 was 1.78 Gy. The mildest clinical sign of local radiation injury was erythema. The received dose was higher than 3 Gy, and the time of onset was from 2 to 3 weeks. In our patient, local radiation injuries (LRIs) did not occur. Though requiring further verification, subsequent bremsstrahlung imaging and estimation of the skin absorbed dose from the subcutaneous infiltration of Sr-89 are useful in confirming Sr-89 extravasation and in the decision making for the choice of treatment strategies for LRIs caused by Sr-89 extravasation. PMID- 27408852 TI - AOJNMB in its second year of publication. PMID- 27408853 TI - In vivo imaging of cellular proliferation in renal cell carcinoma using 18F fluorothymidine PET. AB - OBJECTIVES: The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). METHODS: Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. RESULTS: The SUVmax (maximum standardized uptake value) mean+/-SD for FLT in tumour was 2.59+/-1.27, compared to normal kidney (2.47+/-0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60+/-1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki 67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean +/- SD of 13.3%+/-9.2 (range 2.2% - 36.3%). CONCLUSION: There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology. PMID- 27408854 TI - (18)F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value. AB - OBJECTIVES: Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. METHODS: We analyzed the (18)F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The (18)F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. RESULTS: Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). CONCLUSION: An association exists between high SUV and HER2 overexpression and (18)F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma. PMID- 27408855 TI - Detection of prostate cancer by an FDG-PET cancer screening program: results from a Japanese nationwide survey. AB - OBJECTIVES: The aim of this study was to analyze detection rates and effectiveness of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) cancer screening program for prostate cancer in Japan, which is defined as a cancer-screening program for subjects without known cancer. It contains FDG-PET aimed at detection of cancer at an early stage with or without additional screening tests such as prostate-specific antigen (PSA) and magnetic resonance imaging (MRI). METHODS: A total of 92,255 asymptomatic men underwent the FDG-PET cancer screening program. Of these, 504 cases with findings of possible prostate cancer in any screening method were analyzed. RESULTS: Of the 504 cases, 165 were verified as having prostate cancer. Of these, only 61 cases were detected by FDG PET, which result in 37.0% relative sensitivity and 32.8% positive predictive value (PPV). The sensitivity of PET/computed tomography (CT) scanner was higher than that of dedicated PET (44.0% vs. 20.4%). However, the sensitivity of FDG-PET was lower than that of PSA and pelvic MRI. FDG-PET did not contribute to improving the sensitivity and PPV when performed as combined screening. CONCLUSION: PSA should be included in FDG-PET cancer screening programs to screen for prostate cancer. PMID- 27408856 TI - Influences of reconstruction and attenuation correction in brain SPECT images obtained by the hybrid SPECT/CT device: evaluation with a 3-dimensional brain phantom. AB - OBJECTIVES: The aim of this study was to evaluate the influences of reconstruction and attenuation correction on the differences in the radioactivity distributions in (123)I brain SPECT obtained by the hybrid SPECT/CT device. METHODS: We used the 3-dimensional (3D) brain phantom, which imitates the precise structure of gray matter, white matter and bone regions. It was filled with (123)I solution (20.1 kBq/mL) in the gray matter region and with K2HPO4 in the bone region. The SPECT/CT data were acquired by the hybrid SPECT/CT device. SPECT images were reconstructed by using filtered back projection with uniform attenuation correction (FBP-uAC), 3D ordered-subsets expectation-maximization with uniform AC (3D-OSEM-uAC) and 3D OSEM with CT-based non-uniform AC (3D-OSEM CTAC). We evaluated the differences in the radioactivity distributions among these reconstruction methods using a 3D digital phantom, which was developed from CT images of the 3D brain phantom, as a reference. The normalized mean square error (NMSE) and regional radioactivity were calculated to evaluate the similarity of SPECT images to the 3D digital phantom. RESULTS: The NMSE values were 0.0811 in FBP-uAC, 0.0914 in 3D-OSEM-uAC and 0.0766 in 3D-OSEM-CTAC. The regional radioactivity of FBP-uAC was 11.5% lower in the middle cerebral artery territory, and that of 3D-OSEM-uAC was 5.8% higher in the anterior cerebral artery territory, compared with the digital phantom. On the other hand, that of 3D-OSEM-CTAC was 1.8% lower in all brain areas. CONCLUSION: By using the hybrid SPECT/CT device, the brain SPECT reconstructed by 3D-OSEM with CT attenuation correction can provide an accurate assessment of the distribution of brain radioactivity. PMID- 27408857 TI - Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours. AB - OBJECTIVES: The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). METHODS: 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. RESULTS: (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). CONCLUSION: (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options. PMID- 27408858 TI - Extranodal involvement in lymphoma - A Pictorial Essay and Retrospective Analysis of 281 PET/CT studies. AB - OBJECTIVES: The aim of this study is to evaluate the role of PET-CT in identification of different patterns of extranodal involvement in Hodgkin's disease (HD) and Non-Hodgkin's Lymphoma (NHL) and to enlist the common sites of extranodal involvement in each histological type and compare our results with the existing literature. METHODS: In this retrospective study of 281 cases of lymphomas of various histologies, we illustrate the spectrum of PET/CT features of extranodal lymphoma (ENL) of commonly involved organs and compare our result with the literature. RESULT: Extranodal appearance in lymphoma is strikingly varied. Diffuse large B cell lymphoma (DLBCL) is the commonest histological subtype and gastrointestinal tract is the commonest anatomical subsite in NHL. Skeletal system is the commonest site for involvement in HD. CONCLUSION: A broad spectrum of extranodal organs is involved in various subtype of lymphoma which can be depicted in PET-CT in the most appropriate manner. Familiarity with the pattern of involvement is essential for comprehensive management. PMID- 27408859 TI - (18)F-FDG PET/CT in Neurolymphomatosis: Report of 3 Cases. AB - Neurolymphomatosis is a rare manifestation of non-Hodgkin lymphoma characterized by infiltration of peripheral nerves, nerve roots, plexus and cranial nerves by malignant lymphocytes. This report presents positron emission tomography/computed tomography (PET/CT)imaging with 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F-FDG) in 3 cases of non-Hodgkin lymphoma with nerve infiltration, including one newly diagnosed lymphoma, one recurrent lymphoma in previous nerve lesions and one newly recurrent lymphoma. PET/CT could reveal the affected neural structures including cranial nerves, spinal nerve roots, brachial plexus, cervicothoracic ganglion, intercostal nerves, branches of the vagus nerve, lumbosacral plexus and sciatic nerves. There was relative concordance between PET/CT and MRI in detection of affected cranial nerves. PET/CT seemed to be better than MRI in detection of affected peripheral nerves. (18)F-FDG PET/CT was a whole-body imaging technique with the ability to reveal the affected cranial nerves, peripheral nerves, nerve roots and plexus in non-Hodgkin lymphoma. A thorough understanding of disease and use of advanced imaging modalities will increasingly detect neurolymphomatosis. PMID- 27408860 TI - Early detection of intravascular large B-cell lymphoma by (18)FDG-PET/CT with diffuse FDG uptake in the lung without respiratory symptoms or chest CT abnormalities. AB - Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of systemic extranodal non-Hodgkin diffuse large B-cell lymphoma (DLBCL). We report a rare case of IVLBCL who showed diffuse 18F-fluorodeoxyglucose (FDG) uptake in the lung in FDG-positron emission tomography/computed tomography (PET/CT) without respiratory symptoms or chest CT abnormalities. Serum biochemical studies showed a raised level of lactate dehydrogenase (LDH) and serum soluble interleukin-2 receptor (sIL-2R), which suggested the presence of malignant lymphoma strongly. A non-contrast CT showed no abnormalities in the lung fields, no lymphadenopathy was found. FDG-PET/CT revealed diffuse FDG uptake in the both lungs and in spleen as well as multiple hot spots in the liver. Under the suspicion of IVLBCL especially by the diffuse FDG uptake in the lung, a random skin biopsy was performed from three regions, the left forearm, right abdomen and left thigh in which there had been no evidence of FDG uptake. The definite diagnosis of IVLBCL was made based on the pathological analysis of the specimen from the left thigh. She achieved complete remission (CR) after combined chemoimmunotherapy. FDG PET/CT was useful for the early detection of IVLBCL even without respiratory symptoms or any abnormal findings by chest CT. PMID- 27408861 TI - Usefulness of three-phase bone scintigraphy and SPECT/CT for the diagnosis of bone lesions of systemic sarcoidosis. AB - We report a three-phase bone scintigraphy for the diagnosis of a peripheral bone lesion caused by systemic sarcoidosis. A 32-year-old man with suspected osteomyelitis of the right forefinger underwent three-phase bone scintigraphy with Tc-99m hydroxymethylene diphosphonate (HMDP) and single-photon emission computed tomography/computed tomography (SPECT/CT). The lesion was rich in blood flow according to flow study and blood pool study on bone scintigraphy, and was associated with an osteolytic change on SPECT/CT imaging performed 3 hours after injection of a radioisotope (RI). Whole-body bone scintigraphy indicated multiple high levels of abnormal RI accumulation. The findings of the three-phase bone scintigraphy and SPECT/CT suggested the presence of systemic sarcoidosis; however, a subsequent (18)F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) could not exclude the possibility of multiple metastases from testicular tumors. Therefore, testicular enucleation was performed, and the pathological examination confirmed the presence of sarcoidosis. PMID- 27408862 TI - SPECT/CT imaging in bone scintigraphy of a case of clavicular osteoma. AB - Osteoma is a benign bone-forming tumor that usually arises in the craniofacial bones and rarely in the long bones. Clavicular involvement is extremely rare. We report a 51-year-old woman with osteoma of the left clavicle. Radiograph of the left shoulder showed a well-defined lobulated blastic mass in the proximal and mid-portion of the left clavicle. Bone scintigraphy was performed 4 hours after an intravenous injection of Tc-99m hydroxymethylene diphosphonate (HMDP). Whole body image showed a focus of intensely increased uptake in the clavicle. Single photon emission computed tomography / computed tomography (SPECT/CT) images were also acquired and clearly showed intense uptake at the tumor site. Integrated SPECT/CT imaging supplies both functional and anatomic information about bone the SPECT imaging improves sensitivity compared with planar imaging, the CT imaging provides precise localization of the abnormal uptake, and information on the shape and structure of the abnormalities improves the specificity of the diagnosis. PMID- 27408863 TI - Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience. AB - OBJECTIVES: Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. METHODS: The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in-. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 500 Ga-68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3+/-0.2% for 2011, 76.7+/-0.4% for 2012 and 75.0+/-0.3% for 2013. Ga-68 DOTATATE yields for 2011, 2012, and 2013 were 81.8+/-0.4%, 82.2+/-0.4% and 87.9+/-0.4%, respectively. These exceed the manufacturer's expected value of approximately 70%. Germanium breakthrough averaged 8.6*10(-6)% of total activity which is well below the recommended level of 0.001%. The average ITLC-measured radiochemical purity was above 98.5% and the average HPLC-measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. CONCLUSION: In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga-68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP-compliant and has low maintenance and acceptable running costs. This system together with the recommended (68)Ge/(68)Ga generator is well suited for use in a hospital-based radiopharmacy. PMID- 27408864 TI - Phase IIa Clinical Trial of Trans-1-Amino-3-(18)F-Fluoro-Cyclobutane Carboxylic Acid in Metastatic Prostate Cancer. AB - OBJECTIVES: We performed a phase IIa clinical trial of trans-1-amino-3-(18)F fluoro-cyclobutane carboxylic acid (anti-(18)F-FACBC), a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. METHODS: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-(18)F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti (18)F-FACBC uptake were evaluated from dynamic imaging. RESULTS: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-(18)F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-(18)F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-(18)F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-(18)F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. CONCLUSION: The results of this phase IIa clinical trial indicated the safety of anti-(18)F-FACBC in patients with prostate cancer and the potential of anti-(18)F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326. PMID- 27408865 TI - Development of (111)In-labeled porphyrins for SPECT imaging. AB - OBJECTIVES: The aim of this research was the development of (111)In-labeled porphyrins as possible radiopharmaceuticals for the imaging of tumors. METHODS: Ligands, 5, 10, 15, 20-tetrakis (3, 5-dihydroxyphenyl) porphyrin) (TDHPP), 5, 10, 15, 20-tetrakis (4-hydroxyphenyl) porphyrin (THPP) and 5, 10, 15, 20-tetrakis (3,4-dimethoxyphenyl) porphyrin) (TDMPP) were labeled with (111)InCl3 (produced from proton bombardment of natCd target) in 60 min at 80 oC. Quality control of labeled compounds was performed via RTLC and HPLC followed by stability studies in final formulation and presence of human serum at 37 oC for 48 h as well as partition coefficient determination. The biodistribution studies performed using tissue dissection and SPECT imaging up to 24h. RESULTS: The complexes were prepared with more than 99% radiochemical purity (HPLC and RTLC) and high stability to 48 h. Partition coefficients (calculated as log P) for (111)In TDHPP, (111)In-THPP and (111)In-TDMPP were 0.88, 0.8 and 1.63 respectively. CONCLUSION: Due to urinary excretion with fast clearance for (111)In-TDMPP, this complex is probably a suitable candidate for considering as a possible tumor imaging agent. PMID- 27408866 TI - Effect of Post-Reconstruction Gaussian Filtering on Image Quality and Myocardial Blood Flow Measurement with N-13 Ammonia PET. AB - OBJECTIVES: In order to evaluate the effect of post-reconstruction Gaussian filtering on image quality and myocardial blood flow (MBF) measurement by dynamic N-13 ammonia positron emission tomography (PET), we compared various reconstruction and filtering methods with image characteristics. METHODS: Dynamic PET images of three patients with coronary artery disease (male-female ratio of 2:1; age: 57, 53, and 76 years) were reconstructed, using filtered back projection (FBP) and ordered subset expectation maximization (OSEM) methods. OSEM reconstruction consisted of OSEM_2I, OSEM_4I, and OSEM_6I with 2, 4, and 6 iterations, respectively. The images, reconstructed and filtered by Gaussian filters of 5, 10, and 15 mm, were obtained, as well as non-filtered images. Visual analysis of image quality (IQ) was performed using a 3-grade scoring system by 2 independent readers, blinded to the reconstruction and filtering methods of stress images. Then, signal-to-noise ratio (SNR) was calculated by noise and contrast recovery (CR). Stress and rest MBF and coronary flow reserve (CFR) were obtained for each method. IQ scores, stress and rest MBF, and CFR were compared between the methods, using Chi-square and Kruskal-Wallis tests. RESULTS: In the visual analysis, IQ was significantly higher by 10 mm Gaussian filtering, compared to other sizes of filter (P<0.001 for both readers). However, no significant difference of IQ was found between FBP and various numbers of iteration in OSEM (P=0.923 and 0.855 for readers 1 and 2, respectively). SNR was significantly higher in 10 mm Gaussian filter. There was a significant difference in stress and rest MBF between several vascular territories. However CFR was not significantly different according to various filtering methods. CONCLUSION: Post reconstruction Gaussian filtering with a filter size of 10 mm significantly enhances the IQ of N-13 ammonia PET-CT, without changing the results of CFR calculation. PMID- 27408867 TI - Performance of Myocardial Perfusion Imaging Using Multi-focus Fan Beam Collimator with Resolution Recovery Reconstruction in a Comparison with Conventional SPECT. AB - OBJECTIVES: IQ-SPECT is an advanced high-speed SPECT modality for myocardial perfusion imaging (MPI), which uses a multi-focus fan beam collimator with resolution recovery reconstruction. The aim of this study was to compare IQ-SPECT with conventional SPECT in terms of performance, based on standard clinical protocols. In addition, we examined the concordance between conventional and IQ_SPECT in patients with coronary artery disease (CAD). METHODS: Fifty-three patients, undergoing rest-gated MPI for the evaluation of known or suspected CAD, were enrolled in this study. In each patient, conventional SPECT ((99m)Tc tetrofosmin, 9.6 min and (201)Tl, 12.9 min) was performed, immediately followed by IQ-SPECT, using a short acquisition time (4.3 min for (99m)Tc-tetrofosmin and 6.2 min for (201)Tl). A quantitative analysis was performed on an MPI polar map, using a 20-segment model of the left ventricle. An automated analysis by gated SPECT was carried out to determine the left ventricular volume and function including end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF). The degree of concordance between conventional SPECT and IQ-SPECT images was evaluated according to linear regression and Bland-Altman analyses. RESULTS: The segmental percent uptake exhibited a significant correlation between IQ-SPECT and conventional SPECT (P<0.05). The mean differences in (99m)Tc-tetrofosmin studies were 1.1+/-6.6% (apex), 2.8+/-5.7% (anterior wall), 2.9+/-6.2% (septal wall), 4.9+/-6.7% (lateral wall), and 1.8+/-5.6% (inferior wall). Meanwhile, regarding the (201)Tl-SPECT studies, these values were 1.6+/-6.9%, 2.0+/-6.6%, 2.1+/-5.9%, 3.3+/-7.2%, and 2.4+/-5.8%, respectively. Although the mean LVEF in IQ-SPECT tended to be higher than that observed in conventional SPECT (conventional SPECT=64.8+/-11.8% and IQ SPECT=68.3+/-12.1% for (99m)Tc-tetrofosmin; conventional SPECT= 56.0+/-11.7% and IQ-SPECT=61.5+/-12.2% for (201)Tl), quantitative parameters were not significantly different between IQ-SPECT and conventional SPECT. CONCLUSION: According to the (99m)Tc-tetrofosmin and (201)Tl protocols, IQ-SPECT images were comparable to and in agreement with conventional SPECT images. Our results suggest that IQ-SPECT is a useful technology for MPI SPECT, and can lead to an increase in scan efficiency and patient comfort. PMID- 27408868 TI - Quality Assessment of Research Articles in Nuclear Medicine Using STARD and QUADAS-2 Tools. AB - OBJECTIVES: Diagnostic nuclear medicine is being increasingly employed in clinical practice with the advent of new technologies and radiopharmaceuticals. The report of the prevalence of a certain disease is important for assessing the quality of that article. Therefore, this study was performed to evaluate the quality of published nuclear medicine articles and determine the frequency of reporting the prevalence of studied diseases. METHODS: We used Standards for Reporting of Diagnostic Accuracy (STARD) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklists for evaluating the quality of articles published in five nuclear medicine journals with the highest impact factors in 2012. The articles were retrieved from Scopus database and were selected and assessed independently by two nuclear medicine physicians. Decision concerning equivocal data was made by consensus between the reviewers. RESULTS: The average STARD score was approximately 17 points, and the highest score was 17.19+/-2.38 obtained by the European Journal of Nuclear Medicine. QUADAS-2 tool showed that all journals had low bias regarding study population. The Journal of Nuclear Medicine had the highest score in terms of index test, reference standard, and time interval. Lack of clarity regarding the index test, reference standard, and time interval was frequently observed in all journals including Clinical Nuclear Medicine, in which 64% of the studies were unclear regarding the index test. Journal of Nuclear Cardiology had the highest number of articles with appropriate reference standard (83.3%), though it had the lowest frequency of reporting disease prevalence (zero reports). All five journals had the same STARD score, while index test, reference standard, and time interval were very unclear according to QUADAS-2 tool. Unfortunately, data were too limited to determine which journal had the lowest risk of bias. In fact, it is the author's responsibility to provide details of research methodology so that the reader can assess the quality of research articles. CONCLUSION: Five nuclear medicine journals with the highest impact factor were comparable in terms of STARD score, although they all showed lack of clarity regarding index test, reference standard, and time interval, according to QUADAS-2. The current data were too limited to determine the journal with the lowest bias. Thus, a comprehensive overview of the research methodology of each article is of paramount importance to enable the reader to assess the quality of articles. PMID- 27408869 TI - Serial Myocardial Imaging after a Single Dose of Thallium-201. AB - Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise), showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise). Cardiac biomarkers were negative in the clinical course. PMID- 27408870 TI - Radionuclide Treatment with 153Sm-EDTMP is Effective for the Palliation of Bone Pain in the Context of Extensive Bone Marrow Metastases: A Case Report. AB - Radionuclide therapy is widely used as an effective modality in the management of bone pain. The main indication for this treatment is symptomatic bone metastases, confirmed by bone scintigraphy. We present a case of small cell lung cancer (SCLC) stage T4N2M1b, with a good metabolic response to systemic therapy and radiotherapy of the primary tumor and locoregional disease, which became metabolically less active and remarkably smaller in size (reduction to 1/6 of the original volume). In spite of the good overall response, the patient developed a syndrome with severe bone pain and had progression in the bone marrow metastases, confirmed by (18)F-FDG PET/CT. The patient received (153)Sm-EDTMP treatment with a good clinical response. However, in the whole body bone scan with the therapeutic dose, there was no visual evidence of bone metastasis. Retrospectively, by drawing the region of interest, it was possible to identify one metastatic site. The possible mechanisms of the efficacy of this treatment modality, in this specific setting, are also discussed. PMID- 27408871 TI - Inappropriate Intra-cervical Injection of Radiotracer for Sentinel Lymph Node Mapping in a Uterine Cervix Cancer Patient: Importance of Lymphoscintigraphy and Blue Dye Injection. AB - Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra-cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra-cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra-operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that pre-operative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged. PMID- 27408872 TI - Inflammatory Pseudotumor in the Epidural Space of Lumbosacral Spine on (18)F-FDG PET/CT. AB - An inflammatory pseudotumor (IPT) is a rare benign lesion, characterized by non neoplastic proliferation of inflammatory cells and presence of intermingling collagen fibers. IPT commonly occurs in the lungs and orbita, while an intraspinal IPT is extremely rare. IPT can mimic both clinically and radiologically malignant processes, and making a definitive preoperative diagnosis is often difficult. Recently, 18-fluorine fluorodeoxyglucose ((18)F FDG) has been reported to accumulate in IPT in the lung, spleen, liver, pancreas, colon, orbit, mediastinum, and mesentery. However, to the best of our knowledge, accumulation of (18)F-FDG has not been reported in lumbosacral intraspinal IPT. Herein, we report a case of IPT in the epidural space of the lumbar spine, using the imaging findings of (18)F-FDG positron emission tomography-computed tomography (PET/CT) and contrast-enhanced magnetic resonance imaging (MRI). This is the first case of IPT in the epidural space, depicted by (18)F-FDG PET/CT, which revealed a homogeneous, intense (18)F-FDG uptake. PMID- 27408873 TI - History and Perspectives of Nuclear Medicine in Thailand. PMID- 27408874 TI - AOJNMB changed its publication date; New Year, New Issue! PMID- 27408875 TI - Radiation-induced myocardial perfusion abnormalities in breast cancer patients following external beam radiation therapy. AB - OBJECTIVES: Radiation therapy for breast cancer can induce myocardial capillary injury and increase cardiovascular morbidity and mortality. A prospective cohort was conducted to study the prevalence of myocardial perfusion abnormalities following radiation therapy of left-sided breast cancer patients as compared to those with right-sided cancer. METHODS: To minimize potential confounding factors, only those patients with low 10-year risk of coronary artery disease (based on Framingham risk scoring) were included. All patients were initially treated by modified radical mastectomy and then were managed by postoperative 3D Conformal Radiation Therapy (CRT) to the surgical bed with an additional 1-cm margin, delivered by 46-50 Gy (in 2 Gy daily fractions) over a 5-week course. The same dose-adjusted chemotherapy regimen (including anthracyclines, cyclophosphamide and taxol) was given to all patients. Six months after radiation therapy, all patients underwent cardiac SPECT for the evaluation of myocardial perfusion. RESULTS: A total of 71 patients with a mean age of 45.3+/-7.2 years [35 patients with leftsided breast cancer (exposed) and 36 patients with right sided cancer (controls)] were enrolled. Dose-volume histogram (DVH) [showing the percentage of the heart exposed to >50% of radiation] was significantly higher in patients with left-sided breast cancer. Visual interpretation detected perfusion abnormalities in 42.9% of cases and 16.7% of controls (P=0.02, Odds ratio=1.46). In semiquantitative segmental analysis, only apical (28.6% versus 8.3%, P=0.03) and anterolateral (17.1% versus 2.8%, P=0.049) walls showed significantly reduced myocardial perfusion in the exposed group. Summed Stress Score (SSS) of>3 was observed in twelve cases (34.3%), while in five of the controls (13.9%),(Odds ratio=1.3). There was no significant difference between the groups regarding left ventricular ejection fraction. CONCLUSION: The risk of radiation induced myocardial perfusion abnormality in patients treated with CRT on the left hemi thorax is not low. It is reasonable to minimize the volume of the heart being in the field of radiation employing didactic radiation planning techniques. Also it is advisable to screen these patients with MPI-SPECT, even if they are clinically asymptomatic, as early diagnosis and treatment of silent ischemia may change the outcome. PMID- 27408876 TI - FDG-Avid Portal Vein Tumor Thrombosis from Hepatocellular Carcinoma in Contrast Enhanced FDG PET/CT. AB - OBJECTIVES: In this study, we aimed to describe the characteristics of portal vein tumor thrombosis (PVTT), complicating hepatocellular carcinoma (HCC) in contrast-enhanced FDG PET/CT scan. METHODS: In this retrospective study, 9 HCC patients with FDG-avid PVTT were diagnosed by contrast-enhanced fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), which is a combination of dynamic liver CT scan, multiphase imaging, and whole body PET scan. PET and CT DICOM images of patients were imported into the PET/CT imaging system for the re-analysis of contrast enhancement and FDG uptake in thrombus, the diameter of the involved portal vein, and characteristics of liver tumors and metastasis. RESULTS: Two patients with previously untreated HCC and 7 cases with previously treated HCC had FDG-avid PVTT in contrast-enhanced FDG PET/CT scan. During the arterial phase of CT scan, portal vein thrombus showed contrast enhancement in 8 out of 9 patients (88.9%). PET scan showed an increased linear FDG uptake along the thrombosed portal vein in all patients. The mean greatest diameter of thrombosed portal veins was 1.8 +/- 0.2 cm, which was significantly greater than that observed in normal portal veins (P<0.001). FDG uptake level in portal vein thrombus was significantly higher than that of blood pool in the reference normal portal vein (P=0.001). PVTT was caused by the direct extension of liver tumors. All patients had visible FDG-avid liver tumors in contrast-enhanced images. Five out of 9 patients (55.6%) had no extrahepatic metastasis, 3 cases (33.3%) had metastasis of regional lymph nodes, and 1 case (11.1%) presented with distant metastasis. The median estimated survival time of patients was 5 months. CONCLUSION: The intraluminal filling defect consistent with thrombous within the portal vein, expansion of the involved portal vein, contrast enhancement, and linear increased FDG uptake of the thrombus extended from liver tumor are findings of FDG-avid PVTT from HCC in contrast-enhanced FDG PET/CT. PMID- 27408877 TI - (11)C-Choline and FDG PET/CT Imaging of Primary Cholangiocarcinoma: A Comparative Analysis. AB - OBJECTIVES: This study aimed to compare the diagnostic values of (11)C-choline and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with cholangiocarcinoma (CCA). METHODS: This prospective study was conducted on 10 patients (6 males and 4 females), aged 42 69 years, suspected of having CCA based on CT or magnetic resonance imaging (MRI) results. (11)C-choline and (18)F-FDG PET/CT studies were performed in all patients over 1 week. PET/CT results were visually analyzed by 2 independent nuclear medicine physicians and quantitatively by calculating the tumor-to background ratio (T/B). RESULTS: No (11)C-choline PET/CT uptake was observed in primary extrahepatic or intrahepatic CCA cases. Intense (18)F-FDG avidity was detected in the tumors of 8 patients (%80). Two patients, who were (18)F-FDG negative, had primary extrahepatic CCA. Ki-67 measurements were positive in all patients (range; 14.2%-39.9%). The average T/B values of (11)C-choline and (18)F FDG were 0.4+/-0.2 and 2.0+/-1.0 in all cases of primary CCA, respectively; these values were significantly lower for (11)C-choline (P<0.005). Both FDG and (11)C choline PET/CT detected metastatic CCA foci in all 8 patients (two patients had no metastases). CONCLUSION: As the results suggested, primary CCA lesions showed a poor avidity for (11)C-choline, whereas (18)F-FDG PET/CT was of value for the detection of most primary CCA cases. In contrast to primary lesions, metastatic CCA lesions showed (11)C-choline avidity. PMID- 27408878 TI - Extremity Radioactive Iodine Uptake on Post-therapeutic Whole Body Scan in Patients with Differentiated Thyroid Cancer. AB - OBJECTIVES: We investigated a frequency of lower extremity uptake on the radioactive iodine (RAI) whole body scan (WBS) after RAI treatment in patients with differentiated thyroid cancer, in order to retrospectively examine whether or not the frequency was pathological. METHODS: This retrospective study included 170 patients with thyroid cancer, undergoing RAI treatment. Overall, 99(58%) and 71(42%) patients received single and multiple RAI treatments, respectively. Post therapeutic WBS was acquired after 3 days of RAI administration. For patients with multiple RAI treatments, the WBS of their last RAI treatment was evaluated. Lower extremity uptake on post-therapeutic WBS was classified into 3 categories: bilateral femoral uptake (type A), bilateral femoral and tibia uptake (type B), and uptake in bilateral upper and lower extremities (type C). Then, the patients with RAI uptake in the lower extremities on WBS were analyzed with clinical parameters. RESULTS: Overall, 99 patients (58%) had the extremity uptake on their posttherapeutic RAI WBS. As the results indicated, 42, 53, and 4 patients had type A, type B, and type C uptakes, respectively. Lower extremity uptake was significantly associated with younger age, not only in subjects with multiple RAI treatments but also in all the patients (P<0.05). Accumulation in patients with multiple RAI treatments was more frequent than patients with single RAI treatment (P<0.05). Lower extremity uptake was not associated with counts of the white blood cell count, hemoglobin level, platelet count, estimated glomerular filtration rate, effective half-time of RAI, serum TSH level, and anti-Tg concentration. CONCLUSION: About half of the patients had lower extremity uptake on the posttherapeutic RAI WBS, especially younger patients and those with multiple courses of RAI treatment. Bilateral lower extremity's RAI uptake on the posttherapeutic WBS should be considered as physiological RAI distribution in bone marrow. PMID- 27408879 TI - Production, biodistribution assessment and dosimetric evaluation of (177)Lu-TTHMP as an agent for bone pain palliation. AB - OBJECTIVES: Recently, bone-avid radiopharmaceuticals have been shown to have potential benefits for the treatment of widespread bone metastases. Although (177)Lu-triethylene tetramine hexa methylene phosphonic acid (abbreviated as (177)Lu-TTHMP), as an agent for bone pain palliation, has been evaluated in previous studies, there are large discrepancies between the obtained results. In this study, production, quality control, biodistribution, and dose evaluation of (177)Lu-TTHMP have been investigated and compared with the previously reported data. METHODS: TTHMP was synthesized and characterized, using spectroscopic methods. Radiochemical purity of the (177)Lu-TTHMP complex was determined using instant thin-layer chromatography (ITLC) and high performance liquid chromatography (HPLC) methods. The complex was injected to wild-type rats and biodistribution was studied for 7 days. Preliminary dose evaluation was investigated based on biodistribution data in rats. RESULTS: (177)Lu was prepared with 2.6-3 GBq/mg specific activity and radionuclide purity of 99.98%. (177)Lu TTHMP was successfully prepared with high radiochemical purity (>99%). The complex showed rapid bone uptake, while accumulation in other organs was insignificant. Dosimetric results showed that all tissues received almost insignificant absorbed doses in comparison with bone tissues. CONCLUSION: Based on the obtained results, this radiopharmaceutical can be a good candidate for bone pain palliation therapy in skeletal metastases. PMID- 27408880 TI - Dual radioisotopes simultaneous SPECT of (99m)Tc-tetrofosmin and (123)I-BMIPP using a semiconductor detector. AB - OBJECTIVES: The energy resolution of a cadmium-zinc-telluride (CZT) solid-state semiconductor detector is about 5%, and is superior to the resolution of the conventional Anger type detector which is 10%. Also, the window width of the high energy part and of the low-energy part of a photo peak window can be changed separately. In this study, we used a semiconductor detector and examined the effects of changing energy window widths for (99m)Tc and (123)I simultaneous SPECT. METHODS: The energy "centerline" for (99m)Tc was set at 140.5 keV and that for (123)I at 159.0 keV. For (99m)Tc, the "low-energy-window width" was set to values that varied from 3% to 10% of 140.5 keV and the "high-energy-window width" were independently set to values that varied from 3% to 6% of 140.5 keV. For (123)I, the "low energy-window-width" varied from 3% to 6% of 159.0 keV and the high-energy-window width from 3% to 10% of 159 keV. In this study we imaged the cardiac phantom, using single or dual radionuclide, changing energy window width, and comparing SPECT counts as well as crosstalk ratio. RESULTS: The contamination to the (123)I window from (99m)Tc (the crosstalk) was only 1% or less with cutoffs of 4% at lower part and 6% at upper part of 159KeV. On the other hand, the crosstalk from (123)I photons into the (99m)Tc window mostly exceeded 20%. Therefore, in order to suppress the rate of contamination to 20% or less, (99m)Tc window cutoffs were set at 3% in upper part and 7% at lower part of 140.5 KeV. The semiconductor detector improves separation accuracy of the acquisition inherently at dual radionuclide imaging. In, this phantom study we simulated dual radionuclide simultaneous SPECT by (99m)Tc-tetrofosmin and (123)I-BMIPP. CONCLUSION: We suggest that dual radionuclide simultaneous SPECT of (99)mTc and (123)I using a CZT semiconductor detector is possible employing the recommended windows. PMID- 27408881 TI - Thyroid Nodule Imaging, Status and Limitations. PMID- 27408882 TI - (18)F-FDG PET/CT Imaging of Primary Hepatic Neuroendocrine Tumor. AB - Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare neoplasms. Herein, we report a case of a 70- year-old man with a hepatic mass. The non contrast computed tomography (CT) image showed a low-density mass, and dynamic CT images indicated the enhancement of the mass in the arterial phase and early washout in the late phase. F-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and fused PET/CT images showed increased uptake in the hepatic mass. Whole-body (18)F-FDG PET images showed no abnormal activity except for the liver lesion. Presence of an extrahepatic tumor was also ruled out by performing upper gastrointestinal endoscopy, total colonoscopy, and chest and abdominal CT. A posterior segmentectomy was performed, and histologic examination confirmed a neuroendocrine tumor (grade 1). The patient was followed up for about 2 years after the resection, and no extrahepatic lesions were radiologically found. Therefore, the patient was diagnosed with PHNET. To the best of our knowledge, no previous case of PHNET have been detected by (18)F-FDG PET imaging. PMID- 27408883 TI - SPECT/CT Fusion in the Diagnosis of Hyperparathyroidism. AB - OBJECTIVES: In this study, we aimed to analyze the relationship between the diagnostic ability of fused single photon emission computed tomography/ computed tomography (SPECT/CT) images in localization of parathyroid lesions and the size of adenomas or hyperplastic glands. METHODS: Five patients with primary hyperparathyroidism (PHPT) and 4 patients with secondary hyperparathyroidism (SHPT) were imaged 15 and 120 minutes after the intravenous injection of technetium99m-methoxyisobutylisonitrile ((99m)Tc-MIBI). All patients underwent surgery and 5 parathyroid adenomas and 10 hyperplastic glands were detected. Pathologic findings were correlated with imaging results. RESULTS: The SPECT/CT fusion images were able to detect all parathyroid adenomas even with the greatest axial diameter of 0.6 cm. Planar scintigraphy and SPECT imaging could not detect parathyroid adenomas with an axial diameter of 1.0 to 1.2 cm. Four out of 10 (40%) hyperplastic parathyroid glands were diagnosed, using planar and SPECT imaging and 5 out of 10 (50%) hyperplastic parathyroid glands were localized, using SPECT/CT fusion images. CONCLUSION: SPECT/CT fusion imaging is a more useful tool for localization of parathyroid lesions, particularly parathyroid adenomas, in comparison with planar and or SPECT imaging. PMID- 27408884 TI - High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand. AB - OBJECTIVES: The aim of this study was to determine whether high-dose radioactive iodine (Na(131)I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. METHODS: A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects' willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dosimeter, respectively. RESULTS: Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). CONCLUSION: A safe (131)I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers. PMID- 27408885 TI - Imaging Cellular Proliferation in Prostate Cancer with Positron Emission Tomography. AB - Prostate cancer remains a major public health problem worldwide. Imaging plays an important role in the assessment of disease at all its clinical phases, including staging, restaging after definitive therapy, evaluation of therapy response, and prognostication. Positron emission tomography with a number of biologically targeted radiotracers has been demonstrated to have potential diagnostic and prognostic utility in the various clinical phases of this prevalent disease. Given the remarkable biological heterogeneity of prostate cancer, one major unmet clinical need that remains is the non-invasive imaging-based characterization of prostate tumors. Accurate tumor characterization allows for image-targeted biopsy and focal therapy as well as facilitates objective assessment of therapy effect. PET in conjunction with radiotracers that track the thymidine salvage pathway of DNA synthesis may be helpful to fulfill this necessity. We review briefly the preclinical and pilot clinical experience with the two major cellular proliferation radiotracers, [(18)F]-3'-deoxy-3'-fluorothymidine and [(18)F]-2' fluoro-5-methyl-1-beta-D-arabinofuranosyluracil in prostate cancer. PMID- 27408886 TI - Usefulness of an Automatic Quantitative Method for Measuring Regional Cerebral Blood Flow Using (99m)Tc Ethyl Cysteinate Dimer Brain Uptake Ratio. AB - OBJECTIVES: Improved brain uptake ratio (IBUR), employing (99m)Tc-ethyl cysteinate dimer ((99m)Tc-ECD), is an automatic non-invasive method for quantitatively measuring regional cerebral blood flow (rCBF). This method was developed by the reconstruction of the theory and linear regression equation, based on rCBF measurement by H2 (15)O positron emission tomography. Clarification of differences in rCBF values obtained by Patlak plot (PP) and IBUR method is important for clinical diagnosis during the transition period between these methods. Our purpose in this study was to demonstrate the relationship between rCBF values obtained by IBUR and PP methods and to evaluate the clinical applicability of IBUR method. METHODS: The mean CBF (mCBF) and rCBF values in 15 patients were obtained using the IBUR method and compared with PP method values. RESULTS: Overall, mCBF and rCBF values, obtained using these independent techniques, were found to be correlated (r=0.68). The mCBF values obtained by the IBUR method ranged from 18.9 to 44.9 ml/100g/min, whereas those obtained by the PP method ranged from 34.7 to 48.1 ml/100g/min. The rCBF values obtained by the IBUR method ranged from 16.3 to 60.2 ml/100g/min, whereas those obtained by the PP method were within the range of 26.7-58.8 ml/100g/min. CONCLUSION: The ranges of mCBF and rCBF values, obtained by the IBUR method, were approximately 60% lower than those obtained by the PP method; therefore, this method can be useful for diagnosing lower flow area. Re-analysis of prior PP data, using the IBUR method, could be potentially useful for the clinical follow-up of rCBF. PMID- 27408887 TI - Importance of Defect Detectability in Positron Emission Tomography Imaging of Abdominal Lesions. AB - OBJECTIVES: This study was designed to assess defect detectability in positron emission tomography (PET) imaging of abdominal lesions. METHODS: A National Electrical Manufactures Association International Electrotechnical Commission phantom was used. The simulated abdominal lesion was scanned for 10 min using dynamic list-mode acquisition method. Images, acquired with scan duration of 1-10 min, were reconstructed using VUE point HD and a 4.7 mm full-width at half maximum (FWHM) Gaussian filter. Iteration-subset combinations of 2-16 and 2-32 were used. Visual and physical analyses were performed using the acquired images. To sequentially evaluate defect detectability in clinical settings, we examined two middle-aged male subjects. One had a liver cyst (approximately 10 mm in diameter) and the other suffered from pancreatic cancer with an inner defect region (approximately 9 mm in diameter). RESULTS: In the phantom study, at least 6 and 3 min acquisition durations were required to visualize 10 and 13 mm defect spheres, respectively. On the other hand, spheres with diameters >=17 mm could be detected even if the acquisition duration was only 1 min. The visual scores were significantly correlated with background (BG) variability. In clinical settings, the liver cyst could be slightly visualized with an acquisition duration of 6 min, although image quality was suboptimal. For pancreatic cancer, the acquisition duration of 3 min was insufficient to clearly describe the defect region. CONCLUSION: The improvement of BG variability is the most important factor for enhancing lesion detection. Our clinical scan duration (3 min/bed) may not be suitable for the detection of small lesions or accurate tumor delineation since an acquisition duration of at least 6 min is required to visualize 10 mm lesions, regardless of reconstruction parameters. Improvements in defect detectability are important for radiation treatment planning and accurate PET based diagnosis. PMID- 27408888 TI - Prognostic Value of FDG-PET, Based on the Revised Response Criteria, in Patients with Malignant Lymphoma: A Comparison with CT/MRI Evaluations, Based on the International Working Group/Cotswolds Meeting Criteria. AB - OBJECTIVES: Post-treatment evaluations by CT/MRI (based on the International Working Group/Cotswolds meeting guidelines) and PET (based on Revised Response Criteria), were examined in terms of progression-free survival (PFS) in patients with malignant lymphoma (ML). METHODS: 79 patients, undergoing CT/MRI for the examination of suspected lesions and whole-body PET/CT before and after therapy, were included in the study during April 2007-January 2013. The relationship between post-treatment evaluations (CT/MRI and PET) and PFS during the follow-up period was examined, using Kaplan-Meier survival analysis. The patients were grouped according to the histological type into Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and other histological types. The association between post-treatment evaluations (PET or PET combined with CT/MRI) and PFS was examined separately. Moreover, the relationship between disease recurrence and serum soluble interleukin-2 receptor, lactic dehydrogenase, and C-reactive protein levels was evaluated before and after the treatment. RESULTS: Patients with incomplete remission on both CT/MRI and PET had a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET and those exhibiting incomplete remission on CT/MRI and complete remission on PET (P<0.001). Post-treatment PET evaluations were strongly correlated with patient outcomes in cases with HL or DLBCL (P<0.01) and other histological types (P<0.001). In patients with HL or DLBCL, incomplete remission on both CT/MRI and PET was associated with a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET (P<0.05) and those showing incomplete remission on CT/MRI and complete remission on PET (P<0.01). In patients with other histological types, incomplete remission on both CT/MRI and PET was associated with a significantly shorter PFS, compared to cases with complete remission on both CT/MRI and PET (P<0.001). None of the serum parameters differed significantly between recurrent and non-recurrent cases. CONCLUSION: Post treatment PET evaluations were well correlated with the outcomes of patients with ML, exhibiting FDG uptake. Among patients with HL or DLBCL, a post-treatment complete remission on PET was predictive of a relatively long PFS. For predicting the prognosis of patients with other histological types, a combination of CT/MRI and PET, rather than PET alone, is recommended. PMID- 27408889 TI - Preparation and Quality Control of (68)Ga-Citrate for PET Applications. AB - OBJECTIVES: In nuclear medicine studies, gallium-68 ((8)Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced (68)Ge/(68)Ga generator, a simple technique for the synthesis and quality control of (68)Ga-citrate was introduced; followed by preliminary animal studies. METHODS: (68)GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. (68)Ga citrate was prepared from eluted (68)GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. RESULTS: (68)Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, Fe<0.3 ppm and Zn<0.2 ppm) within 15 min at 500C. The biodistribution of (68)Ga-citrate was consistent with former reports up to 120 minutes. CONCLUSION: This study demonstrated the possible in-house preparation and quality control of (68)Ga citrate, using a commercially available (68)Ge/(68)Ga generator for PET imaging throughout the country. PMID- 27408890 TI - Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System. AB - OBJECTIVES: Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 ((90)Y) and lutetium-177 ((177)Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. METHODS: All syntheses were carried out using the Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer(r) automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) (177)Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 17 [(177)Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [(177)Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 +/- 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 +/- 1.5%) for this period. CONCLUSIONS: The automated synthesis of [(177)Lu]-DOTATATE using Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer(r) system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA (177)Lu and almost negligible radiation exposure of the operators. PMID- 27408891 TI - FDG-PET/CT and CT Findings of a Benign Solitary Fibrous Tumor of the Kidney; Correlation with Pathology. AB - Herein, we report the F-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) findings of a benign solitary fibrous tumor (SFT) of the kidney. The patient was a 63-year-old woman with a mass in the right kidney (10*9.7 cm), incidentally found on CT images. The CT scan showed a lobulated tumor arising from the hilum of the right kidney. The tumor consisted of two components with different patterns of enhancement. Most of the tumor demonstrated moderate enhancement from the corticomedullary to nephrographic phase. A small nodular component at the caudal portion of the tumor showed avid enhancement in the corticomedullary phase and rapid washout in the nephrographic phase in contrast-enhanced CT. FDG-PET/CT was performed and showed weak FDG accumulation (SUVmax=2.30 and 1.91 in the main and small caudal components). Although renal cell carcinoma was preoperatively diagnosed, histopathological examination revealed renal SFT, with no malignant potential. Therefore, when a renal tumor with contrast-medium enhancement and low FDG accumulation is demonstrated, SFT should be considered as a differential diagnosis in addition to renal cell carcinoma. PMID- 27408892 TI - Dual-time-point FDG-PET/CT Imaging of Temporal Bone Chondroblastoma: A Report of Two Cases. AB - Temporal bone chondroblastoma is an extremely rare benign bone tumor. We encountered two cases showing similar imaging findings on computed tomography (CT), magnetic resonance imaging (MRI), and dual-time-point (18)F fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT. In both cases, CT images revealed temporal bone defects and sclerotic changes around the tumor. Most parts of the tumor showed low signal intensity on T2-weighted MRI images and non-uniform enhancement on gadolinium contrast-enhanced T1-weighted images. No increase in signal intensity was noted in diffusion-weighted images. Dual-time-point PET/CT showed markedly elevated (18)F-FDG uptake, which increased from the early to delayed phase. Nevertheless, immunohistochemical analysis of the resected tumor tissue revealed weak expression of glucose transporter-1 and hexokinase II in both tumors. Temporal bone tumors, showing markedly elevated (18)F-FDG uptake, which increases from the early to delayed phase on PET/CT images, may be diagnosed as malignant bone tumors. Therefore, the differential diagnosis should include chondroblastoma in combination with its characteristic findings on CT and MRI. PMID- 27408893 TI - Role of Pre-therapeutic (18)F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma. AB - OBJECTIVES: The present study aimed to evaluate the role of pre-therapeutic (18)fluorine-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) and maximum standardized uptake value (SUVmax) in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of the patients. METHODS: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy), who underwent pre-operative (18)F-FDG PET-CT staging between January 2009 and June 2014. All the patients underwent contrast enhanced CT and non-contrasted (18)F-FDG PET-CT evaluations. The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan Meier product-limit method. RESULTS: In a total of 40 patients, (18)F-FDG PET-CT scan led to changes in disease stage in 26 (65.0%) cases, with upstaging and downstaging reported in 10 (25.0%) and 16 (40.0%) patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the (18)F-FDG PET CT scan alone, the median survival of patients in the palliative group was 4.0 (95% CI 3.0-5.0) months, whereas the median survival in the curative group has not been reached, based on the 12-month follow-up. Selection of treatment strategy on the basis of (18)F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03) and marginally significant at 12 months (P=0.03). On the basis of SUVmax, the relation between survival and SUVmax was not statistically significant. CONCLUSION: (18)F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre-treatment SUVmax failed to stablish its usefulness in the assessment of patient prognosis and survival outcome. PMID- 27408894 TI - Evaluation of Simultaneous Dual-radioisotope SPECT Imaging Using (18)F fluorodeoxyglucose and (99m)Tc-tetrofosmin. AB - OBJECTIVES: Use of a positron emission tomography (PET)/single-photon emission computed tomography (SPECT) system facilitates the simultaneous acquisition of images with fluorine-18 fluorodeoxyglucose ((18)F-FDG) and technetium ((99m)Tc) tetrofosmin. However, (18)F has a short half-life, and 511 keV Compton-scattered photons are detected in the (99m)Tc energy window. Therefore, in this study, we aimed to investigate the consequences of these facts. METHODS: The crosstalk correction for images in the (99m)Tc energy window involved the dual energy window (DEW) subtraction method. In phantom studies, changes in the count of uniform parts in a phantom (due to attenuation from decay), signal detectability in the hot-rod part of the phantom, and the defect contrast ratio in a cardiac phantom were examined. RESULTS: For (18)F-FDG in the step-and-shoot mode, nearly a 9% difference was observed in the count of projection data between the start and end positions of acquisition in the uniform part of the phantom. Based on the findings, the detectability of 12 mm hot rods was relatively poor. In the continuous acquisition mode, the count difference was corrected, and detectability of the hot rods was improved. The crosstalk from (18)F to the (99m)Tc energy window was approximately 13%. In the cardiac phantom, the defect contrast in (99m)Tc images from simultaneous dual-radionuclide acquisition was improved by approximately 9% after DEW correction; the contrast after correction was similar to acquisition with (99m)Tc alone. CONCLUSION: Based on the findings, the continuous mode is useful for (18)F-FDG acquisition, and DEW crosstalk correction is necessary for (99m)Tc-tetrofosmin imaging. PMID- 27408895 TI - Evaluation of Iterative Reconstruction Method and Attenuation Correction in Brain Dopamine Transporter SPECT Using an Anthropomorphic Striatal Phantom. AB - OBJECTIVES: The aim of this study was to determine the optimal reconstruction parameters for iterative reconstruction in different devices and collimators for dopamine transporter (DaT) single-photon emission computed tomography (SPECT). The results were compared between filtered back projection (FBP) and different attenuation correction (AC) methods. METHODS: An anthropomorphic striatal phantom was filled with (123)I solutions at different striatum-to-background radioactivity ratios. Data were acquired using two SPECT/CT devices, equipped with a low-to-medium-energy general-purpose collimator (cameras A-1 and B-1) and a low-energy high-resolution (LEHR) collimator (cameras A-2 and B-2). The SPECT images were once reconstructed by FBP using Chang's AC and once by ordered subset expectation maximization (OSEM) using both CTAC and Chang's AC; moreover, scatter correction was performed. OSEM on cameras A-1 and A-2 included resolution recovery (RR). The images were analyzed, using the specific binding ratio (SBR). Regions of interest for the background were placed on both frontal and occipital regions. RESULTS: The optimal number of iterations and subsets was 10i10s on camera A-1, 10i5s on camera A-2, and 7i6s on cameras B-1 and B-2. The optimal full width at half maximum of the Gaussian filter was 2.5 times the pixel size. In the comparison between FBP and OSEM, the quality was superior on OSEM reconstructed images, although edge artifacts were observed in cameras A-1 and A 2. The SBR recovery of OSEM was higher than that of FBP on cameras A-1 and A-2, while no significant difference was detected on cameras B-1 and B-2. Good linearity of SBR was observed in all cameras. In the comparison between Chang's AC and CTAC, a significant correlation was observed on all cameras. The difference in the background region influenced SBR differently in Chang's AC and CTAC on cameras A-1 and B-1. CONCLUSION: Iterative reconstruction improved image quality on all cameras, although edge artifacts were observed in images captured by cameras with RR. The SBR of OSEM with RR was higher than that of FBP, while the SBR of OSEM without RR was equal to that of FBP. Also, the SBR of Chang's AC varied with different background regions in cameras A-1 and B-1. PMID- 27408896 TI - Validation of Computed Tomography-based Attenuation Correction of Deviation between Theoretical and Actual Values in Four Computed Tomography Scanners. AB - OBJECTIVES: In this study, we aimed to validate the accuracy of computed tomography-based attenuation correction (CTAC), using the bilinear scaling method. METHODS: The measured attenuation coefficient (MUm) was compared to the theoretical attenuation coefficient (MUt), using four different CT scanners and an RMI 467 phantom. The effective energy of CT beam X-rays was calculated, using the aluminum half-value layer method and was used in conjunction with an attenuation coefficient map to convert the CT numbers to MUm values for the photon energy of 140 keV. We measured the CT number of RMI 467 phantom for each of the four scanners and compared the MUm and MUt values for the effective energies of CT beam X-rays, effective atomic numbers, and physical densities. RESULTS: The MUm values for CT beam X-rays with low effective energies decreased in high construction elements, compared with CT beam X-rays of high effective energies. As the physical density increased, the MUm values elevated linearly. Compared with other scanners, the MUm values obtained from the scanner with CT beam X-rays of maximal effective energy increased once the effective atomic number exceeded 10.00. The MUm value of soft tissue was equivalent to the MUt value. However, the ratios of maximal difference between MUm and MUt values were 25.4% (lung tissue) and 21.5% (bone tissue), respectively. Additionally, the maximal difference in MUm values was 6.0% in the bone tissue for each scanner. CONCLUSION: The bilinear scaling method could accurately convert CT numbers to MU values in soft tissues. PMID- 27408898 TI - Preparation and Biological Study of (68)Ga-DOTA-alendronate. AB - OBJECTIVES: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium 68 ((68)Ga). METHODS: DOTA-ALN was synthesized and characterized, followed by (68)Ga-DOTA-ALN preparation, using DOTA-ALN and (68)GaCl3 (pH: 4-5) at 92-95 degrees C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats. RESULTS: The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol) after solid phase purification and was stabilized for up to 90 min with a log P value of -2.91. Maximum ligand binding (65%) was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (<1%) at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection. CONCLUSION: The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors. PMID- 27408897 TI - Physiologically Based Pharmacokinetic (PBPK) Model for Biodistribution of Radiolabeled Peptides in Patients with Neuroendocrine Tumours. AB - OBJECTIVES: The objectives of this work was to assess the benefits of the application of Physiologically Based Pharmacokinetic (PBPK) models in patients with different neuroendocrine tumours (NET) who were treated with Lu-177 DOTATATE. The model utilises clinical data on biodistribution of radiolabeled peptides (RLPs) obtained by whole body scintigraphy (WBS) of the patients. METHODS: The blood flow restricted (perfusion rate limited) type of the PBPK model for biodistribution of radiolabeled peptides (RLPs) in individual human organs is based on the multi-compartment approach, which takes into account the main physiological processes in the organism: absorption, distribution, metabolism and excretion (ADME). The approach calibrates the PBPK model for each patient in order to increase the accuracy of the dose estimation. Datasets obtained using WBS in four patients have been used to obtain the unknown model parameters. The scintigraphic data were acquired using a double head gamma camera in patients with different neuroendocrine tumours who were treated with Lu-177 DOTATATE. The activity administered to each patient was 7400 MBq. RESULTS: Satisfactory agreement of the model predictions with the data obtained from the WBS for each patient has been achieved. CONCLUSION: The study indicates that the PBPK model can be used for more accurate calculation of biodistribution and absorbed doses in patients. This approach is the first attempt of utilizing scintigraphic data in PBPK models, which was obtained during Lu-177 peptide therapy of patients with NET. PMID- 27408899 TI - Hepatosplenic Candidiasis Detected by (18)F-FDG-PET/CT. AB - Hepatosplenic candidiasis is a fungal infection, which mostly affects patients with hematologic malignancies such as leukemia. The pathogenesis of this infection is not clear yet, and the liver is the most commonly affected organ. Diagnosis of hepatosplenic candidiasis can be only established via biopsy, since computed tomography (CT) scan, ultrasonography, and magnetic resonance imaging (MRI) yield non-specific results. The role of fluorine-18 fluorodeoxyglucose positron emission tomography /computed tomography ((18)F-FDG PET/CT) in diagnosis of hepatosplenic candidiasis remains undetermined, considering a few evidences in the literature. In this case report, we present the case of a 47-year-old patient, affected by acute myeloid leukemia, which was treated with three cycles of chemotherapy, resulting in the development of neutropenia and fever following the last cycle. The (18)F-FDG PET/CT scan showed some foci of intense FDG uptake in the liver and spleen. The subsequent diagnostic investigations (i.e., abdominal CT scan and biopsy) were suggestive of hepatosplenic candidiasis. The patient was started on antifungal treatment with fluconazole. After one month, the clinical conditions were resolved, and the subsequent abdominal CT scan was negative. PMID- 27408900 TI - Myocardial Perfusion SPECT Imaging in Dextrocardia with Situs Inversus: A Case Report. AB - Dextrocardia is a cardiac positional anomaly in which the heart is located in the right hemithorax with its base-to-apex axis directed to the right and caudad. Situs inversus is an autosomal recessive disorder that causes organs in the chest and abdomen to be positioned in a mirror image from their normal position. Dextrocardia may occur in isolation or as part of situs inversus. Similarly, situs inversus may occur with or without dextrocardia. Situs inversus accompanied with dextrocardia (situs inversus totalis) is a rare congenital abnormality occurring in 0.01% of live births. Herein, we present the case of a 35-year-old man with previously diagnosed situs inversus totalis with mirror-image dextrocardia, referred to our facility for diagnosis of coronary artery disease (CAD). The incidence and presentation of CAD in patients with dextrocardia are similar to the normal population. However, considerable attention should be paid to the acquisition of myocardial perfusion scintigraphy and data processing/analysis in this group of patients. The present case highlights the distinctive applications and potential pitfalls of myocardial perfusion single photon emission computed tomography (SPECT) imaging in patients with dextrocardia. PMID- 27408901 TI - Nuclear Medicine in the Philippines: A Glance at the Past, a Gaze at the Present, and a Glimpse of the Future. AB - While the introduction of radioactive tracers in the study of metabolic pathways has been well-documented in clinical thyroidology as early as 1924, the widespread utilization in other clinical specialties has been hampered by slow developments in radiation-detecting devices and in the production of appropriate radiopharmaceuticals, in addition to the morbid fear of radiation. In the Philippines, the first radioisotope laboratory was established in 1956. Ten years later, the Philippine Society of Nuclear Medicine was formed. Through the years, challenges were overcome, foundations were laid down, growth was encouraged, friendships with other organizations were built, adjustments were made, and rules were enforced. To date, there are approximately 58 nuclear medicine centers randomly distributed from north to south of the Philippines, 7 accredited nuclear medicine training institutions, 95 board-certified nuclear medicine physicians (a few of whom are also internationally recognized), and a regionally-indexed Philippine Journal of Nuclear Medicine. Qualifying examinations for technologists were also recently instated. International relations are constantly strengthened by sending trainees abroad and accepting foreign trainees here, as well as participating in conferences and other endeavors. While the cost of putting up nuclear medicine centers in the Philippines is still prohibitive, it should not pose too much of a constraint as there are foreign and local parties willing to help. With appropriate instrumentation, targeting radiopharmaceuticals and trained human resources, nuclear medicine can indeed contribute much to health care delivery. PMID- 27408902 TI - Markedly Elevated Liver Enzymes in Choledocholithiasis in the absence of Hepatocellular Disease: Case Series and Literature Review. AB - Liver enzyme levels are commonly obtained in the evaluation of many conditions. Elevated alanine transaminase and aspartate transaminase have traditionally been considered a "hepatocellular" pattern concerning for ischemic, viral, or toxic hepatitis. Elevations in these levels pose a diagnostic dilemma in patients without a clinical picture consistent with liver disease. On the other hand, elevated alkaline phosphatase historically represents a "cholestatic" pattern concerning for gallbladder and biliary tract disease. Often, patients present with a "mixed" picture of elevation in all 3 liver enzymes, further confounding the clinical scenario. We present 4 cases of women with severe upper abdominal pain and markedly elevated transaminases. Three of the patients had accompanying jaundice. A higher rise in enzyme levels was seen in those who had greater bile duct dilation. All patients saw a rapid decrease in transaminases after biliary decompression, along with a fall in alkaline phosphatase and total bilirubin levels. No evidence of liver disease was found, nor were there any signs of hepatocellular disease on imaging. The patients were ultimately found to have choledocholithiasis on endoscopic retrograde cholangiopancreatography with no hepatocellular disease. Furthermore, our cases show that severe abdominal pain in the setting of elevated liver enzymes is likely associated with biliary disease rather than a primary hepatic process. Recognition of this rare pattern of markedly elevated transaminases in isolated biliary disease can aid in avoiding unnecessary evaluation of primary hepatic disease and invasive surgical interventions such as liver biopsy. PMID- 27408903 TI - Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease. AB - Huntington's disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi based therapy for this disease. PMID- 27408904 TI - Multilineage transduction of resident lung cells in vivo by AAV2/8 for alpha1 antitrypsin gene therapy. AB - In vivo gene delivery has long represented an appealing potential treatment approach for monogenic diseases such as alpha1-antitrypsin deficiency (AATD) but has proven challenging to achieve in practice. Alternate pseudotyping of recombinant adeno-associated virus (AAV) vectors is producing vectors with increasingly heterogeneous tropic specificity, giving researchers the ability to target numerous end-organs affected by disease. Herein, we describe sustained pulmonary transgene expression for at least 52 weeks after a single intratracheal instillation of AAV2/8 and characterize the multiple cell types transduced within the lung utilizing this approach. We demonstrate that lung-directed AAV2/8 is able to achieve therapeutic alpha-1 antitrypsin (AAT) protein levels within the lung epithelial lining fluid and that AAT gene delivery ameliorates the severity of experimental emphysema in mice. We find that AAV2/8 efficiently transduces hepatocytes in vivo after intratracheal administration, a finding that may have significance for AAV-based human gene therapy studies. These results support direct transgene delivery to the lung as a potential alternative approach to achieve the goal of developing a gene therapy for AATD. PMID- 27408905 TI - Prevesical Calcification and Hydronephrosis in a Girl Treated for Vesicoureteral Reflux. AB - The endoscopic STING procedure using Deflux is a common and minimal invasive treatment for vesicoureteral reflux. Herein we present the case of an 11-year-old girl with loin pain and de novo hydronephrosis and megaureter on the left. Ultrasound and plain abdominal X-ray demonstrated a calcification at the ureterovesical junction. She had been treated with Deflux injections 5 years before. The clinical quiz addresses the differential diagnosis, workup, and pathogenesis of calcifications at the ureterovesical junction following endoscopic reflux therapy. PMID- 27408907 TI - Data on correlation between Abeta42 structural aggregation propensity and toxicity in bacteria. AB - Protein aggregation and amyloid formation is a hallmark of an increasing number of human disorders. Because protein aggregation is deleterious for the cell physiology and results in a decrease in overall cell fitness, it is thought that natural selection acts to purify aggregating proteins during evolution. This data article contains complementary figures and results related to the research article entitled "Selection against toxic aggregation-prone protein sequences in bacteria" (Navarro et al., 2014) [1]. Here, we used the AGGRESCAN3D (A3D) server, a novel in house predictor that forecasts protein aggregation properties in protein structures to illustrate a striking correlation between the structure based predictions of aggregation propensities for Alzheimer's Abeta42 peptide variants and their previously reported deleterious effects in bacteria. PMID- 27408906 TI - Reinforcement learning with Marr. AB - To many, the poster child for David Marr's famous three levels of scientific inquiry is reinforcement learning-a computational theory of reward optimization, which readily prescribes algorithmic solutions that evidence striking resemblance to signals found in the brain, suggesting a straightforward neural implementation. Here we review questions that remain open at each level of analysis, concluding that the path forward to their resolution calls for inspiration across levels, rather than a focus on mutual constraints. PMID- 27408908 TI - Mass-spectrometry analysis of histone post-translational modifications in pathology tissue using the PAT-H-MS approach. AB - Aberrant histone post-translational modifications (hPTMs) have been implicated with various pathologies, including cancer, and may represent useful epigenetic biomarkers. The data described here provide a mass spectrometry-based quantitative analysis of hPTMs from formalin-fixed paraffin-embedded (FFPE) tissues, from which histones were extracted through the recently developed PAT-H MS method. First, we analyzed FFPE samples from mouse spleen and liver or human breast cancer up to six years old, together with their corresponding fresh frozen tissue. We then combined the PAT-H-MS approach with a histone-focused version of the super-SILAC strategy-using a mix of histones from four breast cancer cell lines as a spike-in standard- to accurately quantify hPTMs from breast cancer specimens belonging to different subtypes. The data, which are associated with a recent publication (Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples (Noberini, 2015) [1]), are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD002669. PMID- 27408909 TI - Observation of an E2 (Ubc9)-homodimer by crystallography. AB - Post-translational modifications by the small ubiquitin-like modifiers (SUMO), in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009) [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2) for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A). This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1), SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015) [2], [3], [4], [5], [6], [7], [8], [9], [10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999) [10], [11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C). The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The data presented here are related to the research article entitled, "RWD domain as an E2 (Ubc9) interaction module" (Alontaga et al., 2015) [10]. The data of the crystal structure has been deposited to RCSB protein data bank with identifier: 4Y1L. PMID- 27408910 TI - X-ray diffraction and NMR data for the study of the location of idebenone and idebenol in model membranes. AB - Here we present some of our data about the interaction of idebenone and idebenol with dipalmitoyl-phosphatidylcholine (DPPC). In particular, we include data of small angle X-ray diffraction (SAXD) and wide angle X-ray diffraction experiments, obtention of electronic profiles of the membranes, (2)H-NMR and (31)P-NMR, as part of the research article: "Both idebenone and idebenol are localized near the lipid-water interface of the membrane and increase its fluidity" (Gomez-Murcia et al., 2016) [1]. These data were obtained from model membranes that included different proportions of idebenone and idebenol, at temperatures both above and below of the gel to fluid phase. The X-ray experiments were carried out by using a modified Kratky compact camera (MBraun Graz-Optical Systems, Graz Austria), incorporating two coupled linear position sensitive detectors. The NMR data were collected from a a Bruker Avance 600 instrument. PMID- 27408911 TI - Data on the role of starch and ammonia in green synthesis of silver and iron oxide nanoparticles. AB - Green synthesis of nanoparticles by using starch has recently attracted considerable attention due to their biodegradability, non-toxicity, and cost effectiveness. The data presented in this article are related to the article entitled "Evaluation of antibacterial activity of Ag/Fe3O4 nanocomposites synthesized by using starch" (Ghaseminezhad and Shojaosadati, 2016) [1]. Here, Fe3O4 nanoparticles and silver nanoparticles were synthesized by using starch under alkaline condition. Hydrodynamic diameter of starch and starch coated silver nanoparticles were determined under heat treatment and different pH. This data also display absorbance peak of silver nanoparticles synthesized by starch under different pH conditions (6.5, 8, and 10). Iodometric titration confirmed that both components of starch (amylose and amylopectin) can adsorb on the surface of Fe3O4 nanoparticles. PMID- 27408913 TI - Datasets for transcriptomic analyses of maize leaves in response to Asian corn borer feeding and/or jasmonic acid. AB - Corn is one of the most widely grown crops throughout the world. However, many corn fields develop pest problems such as corn borers every year that seriously affect its yield and quality. Corn's response to initial insect damage involves a variety of changes to the levels of defensive enzymes, toxins, and communicative volatiles. Such a dramatic change secondary metabolism necessitates the regulation of gene expression at the transcript level. In this paper, we summarized the datasets of the transcriptome of corn plants in response to corn stalk borers (Ostrinia furnacalis) and/or methyl jasmonate (MeJA). Altogether, 39, 636 genes were found to be differentially expressed. The sequencing data are available in the NCBI SRA database under accession number SRS965087. Our dataset will provide more scientific and valuable information for future work such as the study of the functions of important genes or proteins and develop new insect resistant maize varieties. PMID- 27408912 TI - Data on cytochrome c oxidase assembly in mice and human fibroblasts or tissues induced by SURF1 defect. AB - This paper describes data related to a research article entitled "Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects" [1]. This paper includes data of the quantitative analysis of individual forms of respiratory chain complexes I, III and IV present in SURF1 knockout (SURF1 (-/-) ) and control (SURF1 (+/+) ) mouse fibroblasts and tissues and in fibroblasts of human control and patients with SURF1 gene mutation. Also it includes data demonstrating response of complex IV, cytochrome c oxidase (COX), to reversible inhibition of mitochondrial translation in SURF1 (-/-) mouse and SURF1 patient fibroblast cell lines. PMID- 27408914 TI - Validation data of a rabbit antiserum and affinity purified polyclonal antibody against the N-terminus of human GPR30. AB - Rabbit antiserum was generated against the N-terminus of human GPR30 followed by peptide affinity purification. In this article, the methodology used and validation data are presented. The peptide affinity purified polyclonal antibody specifically detects human GPR30 in ELISA and on western blots of total protein prepared from human breast cancer cell lines. PMID- 27408915 TI - Mass spectrometry data for in vitro protein profiles in early and late stages of Douglas-fir xylogenesis. AB - A Douglas-fir tissue culture system was developed [1] that could be induced to differentiate into tracheary elements (fibers) making it possible to monitor xylogenesis in vitro by a proteomics approach. Two proteomes, one from an early and one from a late stage of fiber differentiation process were analyzed and compared. Obtained mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository [2] with the dataset identifiers PXD001484 and DOI:10.6019/ PXD001484 [3]. PMID- 27408916 TI - Glyco-centric lectin magnetic bead array (LeMBA) - proteomics dataset of human serum samples from healthy, Barrett's esophagus and esophageal adenocarcinoma individuals. AB - This data article describes serum glycoprotein biomarker discovery and qualification datasets generated using lectin magnetic bead array (LeMBA) - mass spectrometry techniques, "Serum glycoprotein biomarker discovery and qualification pipeline reveals novel diagnostic biomarker candidates for esophageal adenocarcinoma" [1]. Serum samples collected from healthy, metaplastic Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) individuals were profiled for glycoprotein subsets via differential lectin binding. The biomarker discovery proteomics dataset consisting of 20 individual lectin pull-downs for 29 serum samples with a spiked-in internal standard chicken ovalbumin protein has been deposited in the PRIDE partner repository of the ProteomeXchange Consortium with the data set identifier PRIDE: PXD002442. Annotated MS/MS spectra for the peptide identifications can be viewed using MS-Viewer () using search key "jn7qafftux". The qualification dataset contained 6-lectin pulldown coupled multiple reaction monitoring-mass spectrometry (MRM-MS) data for 41 protein candidates, from 60 serum samples. This dataset is available as a supplemental files with the original publication [1]. PMID- 27408918 TI - Dataset of integrin-linked kinase protein: Protein interactions in cardiomyocytes identified by mass spectrometry. AB - Using hearts from mice overexpressing integrin linked kinase (ILK) behind the cardiac specific promoter alphaMHC, we have performed immunoprecipitation and mass spectrometry to identify novel ILK protein:protein interactions that regulate cardiomyocyte activity and calcium flux. Integrin linked kinase complexes were captured from mouse heart lysates using a commercial antibody, with subsequent liquid chromatography tandem mass spectral analysis. Interacting partners were identified using the MASCOT server, and important interactions verified using reverse immunoprecipitation and mass spectrometry. All ILK interacting proteins were identified in a non-biased manner, and are stored in the ProteomeXchange Consortium via the PRIDE partner repository (reference ID PRIDE: PXD001053). The functional role of identified ILK interactions in cardiomyocyte function and arrhythmia were subsequently confirmed in human iPSC cardiomyocytes. PMID- 27408917 TI - DNA damage response and repair data with pharmacological modulators of Tousled. AB - Human Tousled kinase 1 (TLK1) plays an important role in chromatin remodeling, replication, and DNA damage response and repair. TLK1 activity is immediately, but transiently, downregulated after genotoxic insult, and its recovery is important for exit from checkpoint arrest and cell survival after radiation. The data in this article compliments research presented in the paper titled, "Tousled kinase activator, gallic acid, promotes DNA repair and suppresses radiation cytotoxicity in salivary gland cells" [1]. The identification of small molecule activators and inhibitors of TLK1 provided an opportunity to pharmacologically alter the protein's activity to elucidate its role in DNA damage response pathways. TLK1 effectors, gallic acid (GA) and thioridazine (THD) activate and inhibit the kinase, respectively, and the data report on the impact of these compounds and the significance of TLK1 to DNA break repair and the survival of human salivary acinar cells. PMID- 27408919 TI - Interlaboratory validation data on real-time polymerase chain reaction detection for unauthorized genetically modified papaya line PRSV-YK. AB - This article is referred to research article entitled "Whole genome sequence analysis of unidentified genetically modified papaya for development of a specific detection method" (Nakamura et al., 2016) [1]. Real-time polymerase chain reaction (PCR) detection method for unauthorized genetically modified (GM) papaya (Carica papaya L.) line PRSV-YK (PRSV-YK detection method) was developed using whole genome sequence data (DDBJ Sequenced Read Archive under accession No. PRJDB3976). Interlaboratory validation datasets for PRSV-YK detection method were provided. Data indicating homogeneity of samples prepared for interlaboratory validation were included. Specificity and sensitivity test data for PRSV-YK detection method were also provided. PMID- 27408920 TI - Data on morphology, large-scale chromatin configuration and the occurrence of proteins and rRNA in nucleolus-like bodies of fully-grown mouse oocytes in different fixatives. AB - Here we provide data on accessibility of nucleolus-like bodies (NLBs) of fully grown (GV) mouse oocytes to fluorescence in situ hybridization (FISH) probes and anti-nucleolar antibodies as well as on oocyte general morphology and large scale chromatin configuration, which relate to the research article "High-resolution microscopy of active ribosomal genes and key members of the rRNA processing machinery inside nucleolus-like bodies of fully-grown mouse oocytes" (Shishova et al., 2015 [1]). Experimental factors include: a cross-linking reagent formaldehyde and two denaturing fixatives, such as 70% ethanol and a mixture of absolute methanol and glacial acetic acid (3:1, v/v). PMID- 27408921 TI - Data on the occurrence of corticolous myxomycetes from Denali National Park, Alaska. AB - This data set contains data about corticolous (bark-inhabiting) myxomycetes from a 100*100 m(2) plot including ca. 380 trees of Picea glauca (white spruce), of which 260 were large enough that bark could been sampled to prepare moist chamber cultures. At the end of the data set records of myxomycetes from 66 moist chambers prepared with bark of deciduous trees and shrubs, and outermost twiglets of P. glauca are included. These were sampled around the plot for purposes of comparison. A second data set shows measured tree parameters for the 380 trees examined in the plot. Data were used for a statistical analysis to search for environmental factors decisive for the occurrence of corticolous myxomycetes (Schnittler et al., 2016) [1]. PMID- 27408922 TI - Data on expression of lipoxygenases-5 and -12 in the normal and acetaminophen damaged liver. AB - Here we present additional data on the expression of lipoxygenases -5 and -12 in the normal and acetaminophen-damaged liver, which are associated with our manuscript recently published in Chemico-Biological Interactions on lipid metabolism and eicosanoid signaling pathways involved in acetaminophen-induced liver damage in a mouse model (http://dx.doi.org/10.1016/j.cbi.2015.10.019 [1]). It has been demonstrated that the expression of lipoxygenase-5 and leukotriene formation are increased in the livers of rats with carbon tetrachloride (CCl4) induced cirrhosis (http://dx.doi.org/10.1053/gast.2000.17831 [2]). In addition, the lipoxygenase-12 is known to be expressed in the resident macrophage population of the liver (http://dx.doi.org/10.1016/S0014-5793(99)00396-8 [3]). Mice were injected with acetaminophen, and at 48 h their livers were processed for immunohistochemistry with anti-mouse lipoxygenase-5 and -12 antibodies. At the same time point, the RNA was also extracted from the liver to assess the expression of lipoxygenase-5 and -12 genes via qPCR analysis. Our results show that lipoxygenase-5 expression, but not that of lipoxygenase-12, changes significantly in the acetominophen-damaged liver. PMID- 27408923 TI - Characterization data on the topical carrier DDC642. AB - This article contains original data, figures and methods used in the characterization of the liposomal carrier 'DDC642' for topical applications, described in "An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: proof-of-concept in the treatment of psoriasis" (Desmet et al., 2016) [1]. Several elastic liposomal formulations have been evaluated for their ability to encapsulate and deliver RNA interference (RNAi) molecules to cultured primary skin cells. The efficiency and effectiveness of these liposomes were compared to that of our previously characterized liposomes, the 'SECosomes' (SEC) (Geusens et al., 2010) [2]. After selection of a potential superior carrier, based on encapsulation and transfection efficiency data (Desmet et al., 2016) [1], the selected DDC642 liposomes were characterized more in-depth. Herein, a detailed characterization of the DDC642 liposome and RNAi-loaded lipoplexes is given, including the matching protocols. PMID- 27408924 TI - Data for amino acid alignment of Japanese stingray melanocortin receptors with other gnathostome melanocortin receptor sequences, and the ligand selectivity of Japanese stingray melanocortin receptors. AB - This article contains structure and pharmacological characteristics of melanocortin receptors (MCRs) related to research published in "Characterization of melanocortin receptors from stingray Dasyatis akajei, a cartilaginous fish" (Takahashi et al., 2016) [1]. The amino acid sequences of the stingray, D. akajei, MC1R, MC2R, MC3R, MC4R, and MC5R were aligned with the corresponding melanocortin receptor sequences from the elephant shark, Callorhinchus milii, the dogfish, Squalus acanthias, the goldfish, Carassius auratus, and the mouse, Mus musculus. These alignments provide the basis for phylogenetic analysis of these gnathostome melanocortin receptor sequences. In addition, the Japanese stingray melanocortin receptors were separately expressed in Chinese Hamster Ovary cells, and stimulated with stingray ACTH, alpha-MSH, beta-MSH, gamma-MSH, delta-MSH, and beta-endorphin. The dose response curves reveal the order of ligand selectivity for each stingray MCR. PMID- 27408925 TI - Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs. AB - We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands. PMID- 27408926 TI - Data on electrical energy conservation using high efficiency motors for the confidence bounds using statistical techniques. AB - In this article, we describe details of the data used in the research paper "Confidence bounds for energy conservation in electric motors: An economical solution using statistical techniques" [1]. The data presented in this paper is intended to show benefits of high efficiency electric motors over the standard efficiency motors of similar rating in the industrial sector of Pakistan. We explain how the data was collected and then processed by means of formulas to show cost effectiveness of energy efficient motors in terms of three important parameters: annual energy saving, cost saving and payback periods. This data can be further used to construct confidence bounds for the parameters using statistical techniques as described in [1]. PMID- 27408927 TI - Dataset of protein changes induced by cold acclimation in red clover (Trifolium pratense L.) populations recurrently selected for improved freezing tolerance. AB - The data provide an overview of proteomic changes in red clover (Trifolium pratense L.) in response to cold acclimation and recurrent selection for superior freezing tolerance. Proteins were extracted from crowns of two red clover cultivars grown under non-acclimated or cold-acclimated conditions, and plants obtained from the initial genetic background (TF0) and from populations obtained after three (TF3) and four cycles (TF4) of recurrent selection for superior freezing tolerance. Proteins were analyzed using a two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled to mass spectroscopy (MS and MS/MS). Differentially regulated proteins were subsequently identified using MALDI TOF/TOF analysis. The data are related to a recently published research article describing proteome composition changes associated with freezing tolerance in red clover, "A proteome analysis of freezing tolerance in red clover (Trifolium pratense L.)" (Bertrand et al., 2016 [1]). They are available in the ProteomeXchange Consortium database via the PRIDE partner repository under the dataset identifier PRIDE: PXD003689. PMID- 27408928 TI - Microarray dataset of Jurkat cells following miR-93 over-expression. AB - The dataset presented here represents a microarray experiment of Jurkat cell line over-expressing miR-93 after lentiviral transgenic construct transduction. Three biological replicates have been performed. We further provide normalized and processed data, log2 Fold Change based ranked list and GOterms resulting table. The raw microarray data are available in the ArrayExpress database (www.ebi.ac.uk/arrayexpress) under accession number ArrayExpress: E-MTAB-4588. PMID- 27408929 TI - Genomics dataset of unidentified disclosed isolates. AB - Analysis of DNA sequences is necessary for higher hierarchical classification of the organisms. It gives clues about the characteristics of organisms and their taxonomic position. This dataset is chosen to find complexities in the unidentified DNA in the disclosed patents. A total of 17 unidentified DNA sequences were thoroughly analyzed. The quick response codes were generated. AT/GC content of the DNA sequences analysis was carried out. The QR is helpful for quick identification of isolates. AT/GC content is helpful for studying their stability at different temperatures. Additionally, a dataset on cleavage code and enzyme code studied under the restriction digestion study, which helpful for performing studies using short DNA sequences was reported. The dataset disclosed here is the new revelatory data for exploration of unique DNA sequences for evaluation, identification, comparison and analysis. PMID- 27408930 TI - Deep morphea induced by interferon-beta1b injection. PMID- 27408931 TI - Aquagenic palmoplantar keratoderma with dorsal hand involvement in an adolescent female. PMID- 27408932 TI - Eczema craquele associated with nephrotic syndrome. PMID- 27408933 TI - Pancreatic panniculitis preceding acute pancreatitis and subsequent detection of an intraductal papillary mucinous neoplasm: A case report. PMID- 27408934 TI - Keratoacanthoma-appearing melanoma metastases in a patient receiving pembrolizumab therapy. PMID- 27408935 TI - Cutaneous mucinosis of infancy. PMID- 27408936 TI - Restoration of vaginal anatomy after extensive posterior wall resection utilizing human acellular dermal matrix. PMID- 27408937 TI - Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. AB - INTRODUCTION: Levels of Alzheimer's disease (AD)-related proteins in plasma neuronal derived exosomes (NDEs) were quantified to identify biomarkers for prediction and staging of mild cognitive impairment (MCI) and AD. METHODS: Plasma exosomes were extracted, precipitated, and enriched for neuronal source by anti L1CAM antibody absorption. NDEs were characterized by size (Nanosight) and shape (TEM) and extracted NDE protein biomarkers were quantified by ELISAs. Plasma NDE cargo was injected into normal mice, and results were characterized by immunohistochemistry to determine pathogenic potential. RESULTS: Plasma NDE levels of P-T181-tau, P-S396-tau, and Abeta1-42 were significantly higher, whereas those of neurogranin (NRGN) and the repressor element 1-silencing transcription factor (REST) were significantly lower in AD and MCI converting to AD (ADC) patients compared to cognitively normal controls (CNC) subjects and stable MCI patients. Mice injected with plasma NDEs from ADC patients displayed increased P-tau (PHF-1 antibody)-positive cells in the CA1 region of the hippocampus compared to plasma NDEs from CNC and stable MCI patients. CONCLUSIONS: Abnormal plasma NDE levels of P-tau, Abeta1-42, NRGN, and REST accurately predict conversion of MCI to AD dementia. Plasma NDEs from demented patients seeded tau aggregation and induced AD-like neuropathology in normal mouse CNS. PMID- 27408938 TI - Plasma phospholipids and prevalence of mild cognitive impairment and/or dementia in the ARIC Neurocognitive Study (ARIC-NCS). AB - INTRODUCTION: Phospholipids are altered in brains of patients with dementia and some studies suggest their plasma levels may be useful in the detection of mild cognitive impairment (MCI) and dementia. METHODS: We measured 188 plasma metabolites in participants who underwent a detailed neuropsychological assessment and classified as normal (n = 153), MCI (n = 145), or dementia (n = 143) by expert adjudication. RESULTS: Among 10 phospholipids recently implicated as altered in dementia, higher concentration of PC aa C36:6 was significantly associated with decreased prevalence of dementia (odds ratio = 0.71, 95% confidence interval = 0.50-1.00 per 1-SD increase). Adding these phospholipids to a model including multiple predictors of dementia led to only minimal improvement in detection (C statistic changed from 0.702 to 0.71). DISCUSSION: Some phospholipids and metabolites were altered in MCI and dementia but cross sectional association was relatively weak and did not improve detection of MCI and dementia beyond information provided by clinical variables. PMID- 27408939 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. AB - Many scientists attempt to publish their work in a journal with the highest possible journal impact factor (IF). Despite widespread condemnation of the use of journal IFs to assess the significance of published work, these numbers continue to be widely misused in publication, hiring, funding, and promotion decisions (1, 2). PMID- 27408940 TI - [Comment on "Initial surgical versus conservative strategies in patients with asymptomatic severe aortic stenosis"]. PMID- 27408941 TI - In memoriam Christian Boutin (1933-2015). PMID- 27408943 TI - IN RESPONSE. PMID- 27408942 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY--CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN--2015--EXECUTIVE SUMMARY. PMID- 27408944 TI - Predicting home-clinic blood pressure differences. PMID- 27408945 TI - Blood pressure effects of SGLT2 inhibitors make them an attractive option in diabetic patients with hypertension. PMID- 27408947 TI - Obituary. PMID- 27408946 TI - ARAs to the RESCUE. PMID- 27408948 TI - [Not Available]. PMID- 27408949 TI - The RAB GTPase RABA1e localizes to the cell plate and shows distinct subcellular behavior from RABA2a under Endosidin 7 treatment. AB - Cytokinesis in plants requires the activity of RAB GTPases to regulate vesicle mediated contribution of material to the developing cell plate. While some plant RAB GTPases have been shown to be involved in cell plate formation, many still await functional assignment. Here, we report cell plate localization for YFP RABA1e in Arabidopsis thaliana and use the cytokinesis inhibitor Endosidin 7 to provide a detailed description of its localization compared to YFP-RABA2a. Differences between YFP-RABA2a and YFP-RABA1e were observed in late-stage cell plates under DMSO control treatment, and became more apparent under Endosidin 7 treatment. Taken together, our results suggest that individual RAB GTPases might make different contributions to cell plate formation and further demonstrates the utility of ES7 probe to dissect them. PMID- 27408950 TI - Robert Nussenblatt. PMID- 27408951 TI - High-throughput collagen fingerprinting of intact microfaunal remains; a low cost method for distinguishing between murine rodent bones. AB - RATIONALE: Microfaunal skeletal remains can be sensitive indicators of the contemporary ecosystem in which they are sampled and are often recovered in owl pellets in large numbers. Species identification of these remains can be obtained using a range of morphological criteria established for particular skeletal elements, but typically dominated by a reliance on cranial characters. However, this can induce biases under different environmental and taphonomic conditions. The aim of this research was to develop a high-throughput method of objectively identifying rodent remains from archaeological deposits using collagen fingerprinting, most notably the identification of rats from other myomorph rodents as a means to identify disturbances in the archaeofauna through the presence of invasive taxa not contemporary with the archaeological deposits. METHODS: Collagen was extracted from complete microfaunal skeletal remains in such a manner as to leave the bones morphologically intact (i.e., weaker concentration of acid than previously used over shorter length of time). Acid soluble collagen was then ultrafiltered into ammonium bicarbonate and digested with trypsin prior to dilution in the MALDI matrix and acquisition of peptide mass fingerprints using a matrix-assisted laser desorption/ionisation time-of flight (MALDI-TOF) mass spectrometer. RESULTS: Collagen fingerprinting was able to distinguish between Rattus, Mus, Apodemus and Micromys at the genus level; at the species level, R. rattus and R. norvegicus could be separated whereas A. flavicollis and A. sylvaticus could not. A total of 12,317 archaeological microvertebrate samples were screened for myomorph signatures but none were found to be invasive rats (Rattus) or mice (Mus). Of the contemporary murine fauna, no harvest mice (Micromys) were identified and only 24 field mouse (Apodemus) discovered. CONCLUSIONS: As a result, no evidence of recent bioturbation could be inferred from the faunal remains of these archaeological deposits. More importantly this work presents a method for high-throughput screening of specific taxa and is the first application of collagen fingerprinting to microfaunal remains of archaeological specimens. PMID- 27408952 TI - Assembly of a Metalloporphyrin-Polyoxometalate Hybrid Material for Highly Efficient Activation of Molecular Oxygen. AB - Organic metalloporphyrins and inorganic polyoxometalates (POMs) are two kinds of efficient molecular catalysts to prompt a variety of chemical reactions. They have been used as active moieties for the synthesis of porous materials to realize highly efficient heterogeneous catalysis. Both of them are regarded as the organic/inorganic equivalent counterparts to complement the individual features. Therefore, the combination of metalloporphyrins and POMs in the same hybrid materials might generate interesting catalytic properties by emerging their unique individual functions. To avoid the random connections between metalloporphyrins, POMs, and lanthanide connecting nodes, we have developed a "step-by-step" aggregation strategy, including the reaction of POMs with metal ions to bind metal nodes on the surfaces of POMs at the first step and the reaction of the resulting POM derivatives with metalloporphyrin linkers to result in hybrid materials at the second step. Catalytic experiments demonstrate that the resulting hybrid material exhibits interesting catalytic properties in the heterogeneous epoxidation of olefins, in which the conversion, epoxide selectivity, turnover number, and turnover frequency for the epoxidation of styrene to (1,2-epoxyethyl)benzene are >99%, 94%, 220000, and 22000 h(-1), respectively. These results demonstrate that the collaborative work of multiple active sites in hybrid materials can achieve superior high efficiency in heterogeneous catalysis. PMID- 27408953 TI - Probing Mechanisms for Inverse Correlation between Rate Performance and Capacity in K-O2 Batteries. AB - Owing to the formation of potassium superoxide (K+ + O2 + e- = KO2), K-O2 batteries exhibit superior round-trip efficiency and considerable energy density in the absence of any electrocatalysts. For further improving the practical performance of K-O2 batteries, it is important to carry out a systematic study on parameters that control rate performance and capacity to comprehensively understand the limiting factors in superoxide-based metal-oxygen batteries. Herein, we investigate the influence of current density and oxygen diffusion on the nucleation, growth, and distribution of potassium superoxide (KO2) during the discharge process. It is observed that higher current results in smaller average sizes of KO2 crystals but a larger surface coverage on the carbon fiber electrode. As KO2 grows and covers the cathode surface, the discharge will eventually end due to depletion of the oxygen-approachable electrode surface. Additionally, higher current also induces a greater gradient of oxygen concentration in the porous carbon electrode, resulting in less efficient loading of the discharge product. These two factors explain the observed inverse correlation between current and capacity of K-O2 batteries. Lastly, we demonstrate a reduced graphene oxide-based K-O2 battery with a large specific capacity (up to 8400 mAh/gcarbon at a discharge rate of 1000 mA/gcarbon) and a long cycle life (over 200 cycles). PMID- 27408956 TI - Let's Exercise Our Ingenuity. PMID- 27408957 TI - Letters. PMID- 27408954 TI - Agenda Setting During Follow-Up Encounters in a University Primary Care Outpatient Clinic. AB - At the beginning of the medical encounter, clinicians should elicit patients' agendas several times using open-ended questions. Little is known, however, about how many times physicians really solicit a patient's agenda during follow-up encounters. The objective was to analyze the number of agenda solicitations by physicians, of agendas initiated by physicians, and of patients' spontaneous agendas during the beginning and the entire encounter. We analyzed 68 videotaped follow-up encounters at a university primary care outpatient clinic. The number of different types of agenda setting was searched for and analyzed using negative binomial regression or logistic regression models. Physicians solicited agendas a mean +/- SD of 0.8 +/- 0.7 times/patient during the first 5 minutes and 1.7 +/- 1.2 times/patient during the entire encounter. Physicians in 32.4% of encounters did not solicit the patient agenda, and there were never more than two physician's solicitations during the first 5 minutes. The mean number of physician's solicitations of the patients' agenda was 42% lower among female physicians during the first 5 minutes and 34% lower during the entire encounter. The number of agendas initiated by physicians was 1.2 +/- 1.2/patient during the beginning and 3.2 +/- 2.3/patient during the entire encounter. In 58.8% of the encounters, patients communicated their agendas spontaneously. There were twice as many patient spontaneous agendas (IRR = 2.12, p = .002) with female physicians than with males. This study showed that agenda solicitation with open-ended questions in follow-up encounters does not occur as often as recommended. There is thus a risk of missing new agendas or agendas that are important to the patient. PMID- 27408958 TI - A need to know. PMID- 27408959 TI - Scanning sports. PMID- 27408962 TI - Become as Little Children. PMID- 27408960 TI - Brief reports. PMID- 27408963 TI - Isometric Exercise and the Cardiovascular System. AB - In brief: There is little evidence that isometric exercise benefits the cardiovascular system, and many physicians believe that it imposes undue demands on the myocardium, so they prohibit such exercises for middle-aged or coronary disease patients. This review article examines the validity of this conclusion by summarizing the effects of isometric exercise on heart rate, blood pressure, myocardial demand, cardiac output, peripheral blood flow, and left ventricular function. Dr. Fardy concludes that isometric exercise is less hazardous than has been presumed and says guidelines should be established according to each patient's history. PMID- 27408964 TI - Hepatitis B in an Athlete. AB - In brief: An athlete had an active case of hepatitis B that probably resulted from inadequate sterilization of acupuncture needles five months before the onset of the disease. Therefore, it is important to be sure that acupuncture needles are properly sterilized. PMID- 27408965 TI - On-Field Physician Assessment of High School Football Injuries. AB - In brief: This study analyzed junior and senior high school football injuries with on-the-field evaluation and data collection by physicians. More injuries occurred during varsity than freshman games, and contusions, sprains, strains, and other orthopedic injuries to the extremities were the most common. There was only one concussion in 31 games. This low incidence may be due to more effective football helmets. More injuries occurred on rainy days and muddy fields in this study, which contrasts with previous reports. The authors conclude that the average of one significant injury every five games suggests the need for continued medical coverage at football games. PMID- 27408966 TI - Weight Reduction in Wrestling. AB - In brief: A physician, a psychologist, a physiologist, a wrestling coach, and a wrestler discuss the status of weight reduction in wrestling, including weight classes, methods of weight control, and the physiological effects of those methods. Weight-loss practices such as fasting and dehydration by working out in hot rooms wearing rubber or plastic suits and using saunas, hot boxes, and diuretics have been linked to depression, decreased learning capability, renal problems, and growth reduction. The panelists describe how to determine a wrestler's optimal weight class and discuss the best methods for weight control. PMID- 27408967 TI - Characteristics of National-Class Race Walkers. AB - In brief: Physiological and selected Psychological characteristics of nine highly trained race walkers were studied and the results compared to those for distance runners and other athletes of similar age. The percent body fat of the race walkers was similar to or lower than the other athletes. Their VO2 max of 62.9 ml. kg(-1). min(-1) was significantly higher than active men of comparable age and similar to or higher than many athletes, but significantly lower than world class endurance athletes. PMID- 27408968 TI - Neuromuscular Facilitation Techniques in Sportsmedicine. AB - In brief: One hundred eleven athletic trainers were surveyed about their use of seven neuromuscular facilitation (NF) techniques, what regions of the body they treated with NF, and which NF technique is most effective for a particular injury. Based on the information from this study, N F seems to have three roles: rehabilitation, prevention of injury, and warm-up. NF techniques were used most frequently for injuries to the knee, hip, and shoulder. Hamstring injuries responded best to NF treatment. PMID- 27408969 TI - Coming in sportsmedicine. PMID- 27408970 TI - Exercise-Induced Asthma in Cold Weather. AB - In brief: A 29-year-old distance runner developed wheezing, chest tightness, and cough associated with training or racing in temperatures below 0 C. He had been running for four years and had recently moved to Colorado from Texas. The subject was treated with 2.5 mg of terbutaline orally one hour before running, and his symptoms completely resolved. Premedication was required only during the winter months. This case illustrates that with proper management and premedication tailored to the individual, athletes susceptible to exercise-induced asthma can participate at an essentially normal level throughout the year. PMID- 27408971 TI - Perceived Exertion: One Measure of Exercise Intensity. AB - Gunnar Borg developed the rating of perceived exertion to measure long-term changes in work capacity. Now it is used to monitor exercise programs for at-risk individuals and cardiac patients. PMID- 27408973 TI - Canada: A Model for US Sportsmedicine? AB - The author suggests that a US sportsmedicine council similar to Canada's could benefit both amateur sport and the general public. PMID- 27408972 TI - Joy of Movement: High Priority for Physical Educator. AB - The 'new breed' of physical educators think that physical education classes should teach children the joy of movement rather than arbitrary levels of fitness or sports skills. PMID- 27408974 TI - Sportsmedicine Directory 1981. PMID- 27408975 TI - Meeting notes. PMID- 27408976 TI - Tennis Camp: Days of Challenge, Dreams of Glory. AB - Tennis aficionados will enjoy this comparison of the philosophy, instruction, accommodations, and cost of two intensive weekend tennis camps: All American Sports in Quogue, Long Island, and the Australian Tennis Institute near Tarpon Springs, Florida. PMID- 27408977 TI - Developing Flexibility by Overcoming the Stretch Reflex. PMID- 27408980 TI - Ruthenium-Catalyzed Direct and Selective C-H Cyanation of N-(Hetero)aryl-7 azaindoles. AB - An efficient, highly regioselective, and scalable ruthenium-catalyzed o-aryl C-H mono-cyanation of N-aryl-7-azaindoles to form N-(2-cyanoaryl)-7-azaindoles has been developed through N-directed ortho C-H activation using N-cyano-N-phenyl-p toluenesulfonamide as cyanating reagent in the presence of AgOTf and NaOAc in DCE. A range of substrates has furnished cyanated azaindoles in good to excellent yields under the simple reaction conditions. Involvement of C-H metalation has been supported by a kinetic study. This methodology provides easy access to a class of pharmaceutically significant molecules and their precursors. PMID- 27408982 TI - Triboelectric Nanogenerators for Blue Energy Harvesting. AB - Blue energy in the form of ocean waves offers an enormous energy resource. However, it has yet to be fully exploited in order to make it available for the use of mankind. Blue energy harvesting is a challenging task as the kinetic energy from ocean waves is irregular in amplitude and is at low frequencies. Though electromagnetic generators (EMGs) are well-known for harvesting mechanical kinetic energies, they have a crucial limitation for blue energy conversion. Indeed, the output voltage of EMGs can be impractically low at the low frequencies of ocean waves. In contrast, triboelectric nanogenerators (TENGs) are highly suitable for blue energy harvesting as they can effectively harvest mechanical energies from low frequencies (<1 Hz) to relatively high frequencies (~kHz) and are also low-cost, lightweight, and easy to fabricate. Several important steps have been taken by Wang's group to develop TENG technology for blue energy harvesting. In this Perspective, we describe some of the recent progress and also address concerns related to durable packaging of TENGs in consideration of harsh marine environments and power management for an efficient power transfer and distribution for commercial applications. PMID- 27408983 TI - Tensiometric Characterization of Superhydrophobic Surfaces As Compared to the Sessile and Bouncing Drop Methods. AB - We have considered in this work the Wilhelmy plate tensiometer to characterize the wetting properties of two model surface textures: (i) a series of three superhydrophobic micropillared surfaces and (ii) a series of two highly water repellent surfaces microtextured with a femtosecond laser. The wetting forces obtained on these surfaces with the Wilhelmy plate technique were compared to the contact angles of water droplets measured with the sessile drop technique and to the bouncing behavior of water droplets recorded at a high frame rate. We showed that it is possible with this technique to directly measure triple-line anchoring forces that are not accessible with the commonly used sessile drop technique. In addition, we have demonstrated on the basis of the bouncing drop experiments wetting transitions induced by the specific test conditions associated with the Wilhelmy plate tensiometer for the two series of textured surfaces. Finally, the tensiometer technique is proposed as an alternative test for characterizing the wetting properties of highly liquid-repellent surface, especially under immersion conditions. PMID- 27408981 TI - Parkinson's disease psychosis: therapy tips and the importance of communication between neurologists and psychiatrists. AB - Parkinson's disease (PD) is a chronic and complex neurodegenerative disorder resulting in a mixture of motor and nonmotor symptoms. Psychosis develops in around 60% of PD patients during and can be one of the most challenging nonmotor symptoms. PD psychosis is considered the single greatest precipitant for nursing home placement. PD psychosis is an independent predictor of increased mortality, and there is no 'ideal' or universal treatment strategy. The treatment approach to PD psychosis should be tailored and individualized for each patient. In this review, we will discuss PD psychosis and provide practical treatment considerations for neurologists, psychiatrists and other healthcare professionals. We stress the importance of real-time communication between members of the healthcare team. PMID- 27408984 TI - Parents' socioeconomic factors related to high antibiotic prescribing in primary health care among children aged 0-6 years in the Capital Region of Denmark. AB - OBJECTIVE: To investigate the distribution of antibiotic prescriptions in primary health care among children aged 0-6 years and its association with socioeconomic factors. DESIGN: A cross-sectional study describing antibiotic prescriptions and socioeconomic factors, using different population-based registers from Statistics Denmark. SETTING: Antibiotic prescriptions in 2012 from primary health care in the Capital Region of Denmark. SUBJECTS: The population of children aged 0-6 years (n = 139,398) in the Capital Region of Denmark. MAIN OUTCOME MEASURES: High use of antibiotics identified by number of antibiotic prescriptions (>= 3 prescriptions per year) and defined daily doses (DDD). A multinomial logistic regression analysis estimating the association between high antibiotic use and parents' education, employment status, income, child's sex, and ethnic background. RESULTS: Ten percent of children accounted for 25% of the total use DDD. There was a clear tendency that the risk for high antibiotic use increased as parental educational level decreased. The risk for high use was the highest among children of mothers and fathers with basic schooling <=10 years (OR 1.60, 95% CI 1.29-1.98, and OR 1.60, 95% CI 1.34-1.91, respectively). Low income and unemployment were not associated with high antibiotic use. CONCLUSION: Socioeconomic factors can only partially explain differences in antibiotic use. Further research is needed to clarify the unequal distribution of antibiotic prescribing and the association between high antibiotic use and low educational level. This would provide valuable information in the planning of strategies to promote rational use of antibiotics among children. KEY POINTS The Capital Region of Denmark has the highest rate of antibiotic prescribing in Denmark. Preschool children are among the age groups with the highest use. Ten percent of the children accounted for 25% of the total antibiotic use. Low parental educational level was associated with increased antibiotic use. Parents' income or employment status was not found to be associated with high antibiotic use. PMID- 27408985 TI - The cardioprotective effect of naringenin against ischemia-reperfusion injury through activation of ATP-sensitive potassium channel in rat. AB - Naringenin (Nari) has antioxidative and anti-atherosclerosis effects, and activation of ATP-sensitive potassium channel (KATP) can offer cardiac protection. We hypothesized that Nari protects the heart against ischemia reperfusion (I-R) injury through activation of KATP. Isolated hearts from adult male Sprague-Dawley rats experienced a 30-min global ischemia followed by 60-min reperfusion (120 min for the infarct size determination). The hearts were treated with Nari (NARI); Nari plus glibenclamide (GLI), a non-specific ATP-sensitive potassium channel blocker (NARI+GLI); and Nari plus 5-hydroxy decanoic acid (5 HD), a mitochondrial membrane ATP-sensitive potassium channel blocker (NARI+5 HD). The left ventricular pressure, lactate dehydrogenates (LDH) in coronary effluent, superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardium, and myocardial infarct area were measured. Nari above 2.5 MUmol/L improved the recovery of left ventricular function, decreased LDH in coronary effluent, and reduced myocardial infarct area. The SOD activity was increased and MDA was decreased in Nari-treated myocardium. The cardioprotective effect of Nari was canceled by GLI and 5-HD. In conclusion, Nari has a cardioprotective effect against I-R injury, which may be carried out through activating ATP-sensitive potassium channels in both cell and mitochondrial membrane, and enhancing myocardial antioxidant capacity. PMID- 27408986 TI - Effect of solids retention time on nitrogen and phosphorus removal from municipal wastewater in a sequencing batch membrane bioreactor. AB - This study evaluated the removal of organic matter, nitrogen and phosphate from a municipal wastewater in a sequencing batch membrane bioreactor (SBMBR) operated at different solids retention times (SRTs) and subjected to different aeration profiles. The results demonstrated that SRT reduction from 80 to 20 d had a negligible effect on chemical oxygen demand (COD) removal and only a slight negative effect on nitrification. COD removal efficiency remained stable at 97%, whereas ammonium removal decreased from 99% to 97%. The total nitrogen removal efficiency was improved by SRT reduction, increasing from 80% to 86%. Although the total phosphorus (TP) removal was not significantly affected by the SRT reduction, ranging from 40-49%, the P-release and P-uptake processes were observed to increase as the SRT was reduced. The implementation of a pre-aeration phase in the SBMBR operating cycle allowed a higher TP removal performance, which reached up to 76%. Batch tests suggested that the fraction of phosphate removed anoxically from the total (anoxic + aerobic) phosphate removal decreased with the SRT reduction. PMID- 27408987 TI - Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation. AB - To determine the effects of a mushroom blend containing Cordyceps militaris on high-intensity exercise after 1 and 3 weeks of supplementation. Twenty-eight individuals (Mean +/- standard deviation [SD]; Age = 22.7 +/- 4.1 yrs; Height = 175.4 +/- 8.7 cm; Weight = 71.6 +/- 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (%drop) were recorded during a 3 minute maximal cycle test with resistance at 4.5% body weight. Subjects consumed 4 g.d-1 mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks. Exercise tests were separated by at least 48 hours and repeated following supplementation periods. One week of supplementation elicited no significant time * treatment interaction for VO2max (p = 0.364), VT (p = 0.514), TTE (p = 0.540), RPP (p = 0.134), AvgP (p = 0.398), or %drop (p = 0.823). After 3 weeks, VO2max significantly improved (p = 0.042) in MR (+4.8 ml.kg-1.min-1), but not PL (+0.9 ml.kg-1.min-1). Analysis of 95% confidence intervals revealed significant improvements in TTE after 1- (+28.1 s) and 3 weeks (+69.8 s) in MR, but not PL, with additional improvements in VO2max (+4.8 ml.kg-1.min-1) and VT (+0.7 l.min-1) after 3 weeks. Acute supplementation with a Cordyceps militaris containing mushroom blend may improve tolerance to high-intensity exercise; greater benefits may be elicited with consistent chronic supplementation. PMID- 27408988 TI - Continuous Fluorescence Imaging of Intracellular Calcium by Use of Ion-Selective Nanospheres with Adjustable Spectra. AB - Continuous fluorescence imaging of intracellular ions in various spectral ranges is important for biological studies. In this paper, fluorescent calcium-selective nanospheres, including calix[4]arene-functionalized bodipy (CBDP) or 9 (diethylamino)-5-[(2-octyldecyl)imino]benzo[a]phenoxazine (ETH 5350) as the chromoionophore, were prepared to demonstrate intracellular calcium imaging in visible or near-IR regions, respectively. The fluorescence of the nanospheres was controlled by the chromoionophore, and thus the spectral range for detection was adjustable by choosing the proper chromoionophore. The response time of the nanospheres to calcium was typically 1 s, which allowed accurate measurement of intracellular calcium. These nanospheres were loaded into cells through free endocytosis and exhibited fluorescence for 24 h, and their intensity was correlated with the elevation of intracellular calcium upon stimulation. The successful demonstration of calcium imaging by use of ion-selective nanospheres within two spectral ranges in 24 h supported that these nanospheres could be applied for continuous imaging of intracellular ions with adjustable spectra. PMID- 27408989 TI - Jatropha curcas and assisted phytoremediation of a mine tailing with biochar and a mycorrhizal fungus. AB - Soil pollution is an important ecological problem worldwide. Phytoremediation is an environmental-friendly option for reducing metal pollution. A greenhouse experiment was conducted to determine the growth and physiological response, metal uptake, and the phytostabilization potential of a nontoxic Jatropha curcas L. genotype when grown in multimetal-polluted conditions. Plants were established on a mine residue (MR) amended or not amended with corn biochar (B) and inoculated or not inoculated with the mycorrhizal fungus Acaulospora sp. (arbuscular mycorrhizal fungus, AMF). J. curcas was highly capable of growing in an MR and showed no phytotoxic symptoms. After J. curcas growth (105 days), B produced high desorption of Cd and Pb from the MR; however, no increases in metal shoot concentrations were observed. Therefore, Jatropha may be useful for phytostabilization of metals in mine tailings. The use of B is recommended because improved MR chemical properties conduced to plant growth (cation-exchange capacity, organic matter content, essential nutrients, electrical conductivity, water-holding capacity) and plant growth development (higher biomass, nutritional and physiological performance). Inoculation with an AMF did not improve any plant growth or physiological plant characteristic. Only higher Zn shoot concentration was observed, but it was not phytotoxic. Future studies of B use and its long term effect on MR remediation should be conducted under field conditions. PMID- 27408990 TI - Pembrolizumab: the value of PDL1 biomarker in head and neck cancer. PMID- 27408991 TI - Dramatic treatment response of cutaneous plasmablastic lymphoma in an HIV patient: a case report. AB - Plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma, characterized by rapid progression and is associated with a poor outcome. We report a 35-year-old male with poorly controlled HIV infection and AIDS who presented with skin lesions and swelling throughout the body. Computed tomography (CT) revealed innumerable enhancing soft tissue masses within the subcutaneous soft tissues and lymphadenopathy. Plasmablastic lymphoma was diagnosed, patient was treated with chemotherapy, and post treatment CT demonstrated complete resolution. Imaging plays a key role in the diagnosis and surveillance of this disease. PMID- 27408992 TI - Ultrasound shear wave elastography in assessment of muscle stiffness in patients with Parkinson's disease: a primary observation. AB - OBJECTIVE: The aim of this study was to assess the capability of ultrasound shear wave elastography (SWE) in evaluating the muscle stiffness in patients with Parkinson's diseases (PD). METHODS: Ultrasound SWE of the longitudinal biceps brachii was performed on 46 patients with PD and 31 healthy controls from May 2013 to October 2013. The stiffness of the biceps brachii muscles measured with quantitative Young's modulus (kPa) was compared between the remarkably symptomatic arms and mildly symptomatic arms in the PD and between PD and controls with unpaired t test. The correlation between the Young's modulus of the biceps brachii measured by SWE and motion scores assessed by unified Parkinson's disease rating scale (UPDRS) part III was analyzed by Pearson's correlation coefficient. The reliability of SWE in assessment of biceps brachii stiffness was tested using intraclass correlation coefficient (ICC). RESULTS: The mean Young's modulus of biceps brachii in remarkably symptomatic arms, mildly symptomatic arms, and healthy controls was 59.94+/-20.91 kPa, 47.77+/-24.00 kPa, and 24.28+/ 5.09 kPa, respectively. A significant difference in Young's modulus of biceps brachii was found between healthy controls and all PD patients (all P<.05); however, it was not between remarkably symptomatic and mildly symptomatic arms. A positive linear correlation was found between the Young's modulus of the biceps brachii and the motion score by UPDRS in patients with PD (r=0.646, P=.000). The ICC for interobserver and intraobserver variation in measuring Young's modulus of the biceps brachii with SWE was 0.74 (95% confidence interval 0.68-0.78) and 0.78 (95% confidence interval 0.75-0.82), respectively. CONCLUSIONS: SWE of the biceps brachii can be used as a quantitative assessment of muscle stiffness in the patients with PD. PMID- 27408993 TI - A Fast Progressing, Space-Occupying Lesion on the Brain of an HIV-Infected Patient. PMID- 27408994 TI - Intrinsic Negative Poisson's Ratio for Single-Layer Graphene. AB - Negative Poisson's ratio (NPR) materials have drawn significant interest because the enhanced toughness, shear resistance, and vibration absorption that typically are seen in auxetic materials may enable a range of novel applications. In this work, we report that single-layer graphene exhibits an intrinsic NPR, which is robust and independent of its size and temperature. The NPR arises due to the interplay between two intrinsic deformation pathways (one with positive Poisson's ratio, the other with NPR), which correspond to the bond stretching and angle bending interactions in graphene. We propose an energy-based deformation pathway criteria, which predicts that the pathway with NPR has lower energy and thus becomes the dominant deformation mode when graphene is stretched by a strain above 6%, resulting in the NPR phenomenon. PMID- 27408995 TI - In Memoriam J.C. Lavigne, past president RBSS 1982. PMID- 27408996 TI - Effect of Human Breast Milk on the Expression of Proinflammatory Cytokines in Caco-2 Cells after Hypoxia/Re-Oxygenation. AB - BACKGROUND: Neonatal necrotizing enterocolitis is a common and often fatal gastrointestinal disease, especially in premature infants. To study potential mechanisms underlying the protective effect of breast milk on neonatal necrotizing enterocolitis, we induced intestinal inflammation in a Caco-2 cell model of neonatal necrotizing enterocolitis by hypoxia/re-oxygenation to investigate whether breast milk supernatant fluid inhibited the expression of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha. METHODS: Caco-2 cells were divided into normal (control) and neonatal necrotizing enterocolitis groups. Neonatal necrotizing enterocolitis was mimicked by exposing Caco-2 cells to hypoxia/re-oxygenation. Cells were independently maintained in minimal essential medium alone, minimal essential medium containing 5% breast milk supernatant, or 5% boiled breast milk supernatant. Production of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was investigated in cell culture supernatants by ELISA, reverse transcription polymerase chain reaction, and immunofluorescence. RESULTS: Hypoxia/re-oxygenation significantly increased the expression of interleukin 1beta, interleukin-6, and tumor necrosis factor-alpha. In the normal group, breast milk supernatant and boiled breast milk supernatant markedly downregulated the expression of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha when compared with the minimal essential medium group, with the reduction in inter-leukin-1beta expression being more pronounced in the breast milk group. In Caco-2 cells undergoing hypoxia/re-oxygenation, both breast milk supernatant and boiled breast milk supernatant significantly reduced the expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, where the decrease in interleukin-1beta expression was greater in the breast milk group. CONCLUSIONS: Breast milk supernatant fluid inhibited the expression of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in Caco-2 cells, especially after hypoxia/re-oxygenation. This may be one of the mechanisms underlying the protective effect of breast milk on neonatal necrotizing enterocolitis. PMID- 27408997 TI - Clinical Benefit of 3 Tesla Magnetic Resonance Imaging Rescanning in Patients With Focal Epilepsy and Negative 1.5 Tesla Magnetic Resonance Imaging. AB - BACKGROUND: Magnetic resonance imaging is an essential tool in the pre-surgical evaluation of patients with drug-resistant epilepsy. OBJECTIVE: Our aim was to assess the value of re-imaging patients with focal drug-resistant epilepsy. METHODS: Thirty patients with negative or non-conclusive 1.5 Tesla magnetic resonance imaging were rescanned with 1.5T and 3T. All of them had previous 1.5 scans with no seizure protocol in a non-specialized center. Two neuroradiologists who were blinded to prior imaging results randomly reviewed the magnetic resonance images. Kappa score was used to assess the reliability. RESULTS: Mean age of patients was 30 (SD +/- 11) years. The intra-observer agreement for the first radiologist was 0.74 for 1.5T and 0.71 for 3T. In the second radiologist it was 0.82 and 0.66, respectively. Three lesions (10%) were identified by general radiologists in non-specialized centers using a 1.5T standard protocol. In our center a consensus between two neuroradiologists using epilepsy protocol identified seven lesions (23%) using 1.5T and 10 (33%) using 3T (p < 0.01). In 28% of patients this additional information resulted in a change in clinical management. CONCLUSIONS: 3T magnetic resonance imaging rescanning improves the diagnostic yield in patients with focal epilepsy and previous negative 1.5T magnetic resonance imaging. Use of 3T magnetic resonance imaging, epilepsy protocols, and interpretation by experienced neuroradiologists is highly recommended. PMID- 27408998 TI - Effect of Passive Smoking on the Growth of Pulmonary Function and Respiratory Symptoms in Schoolchildren. AB - BACKGROUND: Environmental tobacco smoke affects the current and future health of children. OBJECTIVE: To determine whether schoolchildren aged 8-17 years old residing at an altitude of 2,240 m and exposed to tobacco smoke at home presented a reduction in the growth of pulmonary function and a greater problem of respiratory symptoms and infections compared with non-exposed children. MATERIALS AND METHODS: We followed, with questionnaires and spirometry, 1,632 boys and 1,555 girls from Mexico City and its metropolitan area (the Metropolitan Study to Evaluate the Chronic Effects of Pollution in School-age Children [EMPECE]) every six months for six years. The impact of passive smoking was estimated by mixed effects models and Generalized Linear and Latent Mixed Models (GLLAMM), stratifying by gender and adjusting for age, height, weight, and ozone levels. RESULTS: Passive smoking (reported by one-half of participants) was associated with reduced spirometric lung function (log transformed or as Z-scores) and a higher frequency of self-reported respiratory symptoms and respiratory infections. Levels of forced expiratory volume in 1 second and forced vital capacity in individuals exposed to passive smoking were 6.8 and 14.1 ml, respectively, below those of non-exposed children, and these values decreased with increasing number of smokers at home and higher ozone levels. CONCLUSIONS: Passive smoking in children is a significant risk factor for respiratory disease and reduced lung function growth, which are additive with levels of air pollution, asthma, and the presence of respiratory symptoms. PMID- 27408999 TI - HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes. AB - BACKGROUND: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific beta-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes. OBJECTIVE: To evaluate the association of HLA risk haplotype HLA-DRB1/ DQA1/-DQB1 with beta-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls. METHODS: We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and beta-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data. RESULTS: We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*03:02, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype. CONCLUSIONS: The DRB1*04/DQA1*03/DQB1*03:02 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population. PMID- 27409000 TI - Globe Salvage With Intra-Arterial Topotecan-Melphalan Chemotherapy in Children With a Single Eye. AB - INTRODUCTION: Intra-arterial chemotherapy is a novel therapeutic modality for retinoblastoma patients. Intra-arterial chemotherapy involves the administration of a super-selective drug through the ophthalmic artery, resulting in better ocular penetration and low systemic toxicity. OBJECTIVE: The aim of this report was to evaluate the feasibility of intra-arterial chemotherapy in a large referral center in Mexico City. METHODS: We included patients with bilateral retinoblastoma, one enucleation, and active disease in the other eye after at least two courses of systemic chemotherapy combined with topical treatments. All patients were treated with three courses of a combination of melphalan 4 mg and topotecan 1 mg. Patients were examined under general anesthesia three weeks after each chemotherapy cycle. RESULTS: From 14 eligible patients, three could not be treated due to inaccessibility of the ophthalmic artery. A complete response was observed in 5/11 patients, three in Stage C according to the International Classification for Intraocular Retinoblastoma, one in Stage D, and one in Stage B. The eyes of three patients were enucleated as a result of active/progressive disease, one in Stage B and two in Stage D. Eye preservation was 55% after a mean follow-up of 171 days (range 21-336). CONCLUSIONS: Super-selective intra-arterial chemotherapy is safe and effective for preventing the enucleation of 55% of affected eyes in this group of patients. PMID- 27409002 TI - Clinical Characteristics and Mortality of Influenza A H1N1 and Influenza-Like Illness in Mexico City in the 2013-2014 Winter Season. AB - BACKGROUND: The 2013-2014 influenza season in Mexico City was severe and mainly due to influenza A H1N1, as was the 2009 pandemic. OBJECTIVE: To describe features of the outbreak and to compare the characteristics of patients with and without viral identification. METHODS: We reviewed the medical charts of all individuals with influenza or influenza-like illness admitted to a referral hospital for respiratory diseases in Mexico City from January 2013 to March 2014, whether influenza virus was identified or not. RESULTS: We included 233 patients with influenza-like illness, 99 of whom had laboratory confirmed influenza; one half of all patients required mechanical ventilation and 25% were admitted to the intensive care unit. Patients with confirmed influenza had a more severe disease than those without confirmation. A total of 52 (22.3%) patients died in hospital; survival was greater among patients hospitalized in the intensive care unit compared with those who remained in regular wards. CONCLUSIONS: Influenza A H1N1 continues to cause significant outbreaks in Mexico City. Patients with influenza like illness had a similar clinical course regardless of laboratory confirmation of influenza, suggesting that their illness likely belonged to the same outbreak. Mechanical ventilation in regular hospital wards may be lifesaving, although the outcome is worse than at an intensive care unit. PMID- 27409001 TI - Lethal Keratitis, Ichthyosis, and Deafness Syndrome Due to the A88V Connexin 26 Mutation. AB - Keratitis-ichthyosis-deafness syndrome is a well-characterized disease that has been related to mutations in the GJB6 gene. Clinical features such as erythrokeratoderma, palmoplantar keratoderma, alopecia, and progressive vascularizing keratitis, among others, are well known in this entity. In this report we describe a newborn female patient diagnosed with keratitis-ichthyosis deafness syndrome with a lethal outcome due to sepsis. The patient harbored the mutation A88V that has been previously reported in lethal cases. PMID- 27409004 TI - Suicide Among Farmers in France: Occupational Factors and Recent Trends. AB - Numerous studies have found agricultural workers, including farmers, at elevated risk of suicide, and socioeconomic conditions have been suggested as one of the important determinants of this mortality cause. The real agricultural income per worker in Europe increased steadily from 2005 to 2007 and then fell by 1.8% in 2008 and by 11.6% in 2009. This drop was particularly pronounced in France. Repeated cross-sectional studies were conducted to investigate suicide mortality rates among French farmers in 2007-2009. The study population included all French farmers enrolled yearly in the compulsory Agricultural Social Security and Health Insurance (CCMSA). Most of the mean of 500,164 subjects per year were men (68%). National cause-specific mortality rates were used to calculate standardized mortality ratios (SMRs) and associated 95% confidence intervals (95% CIs) for both genders and for each of the 3 years. During the 3-year study period, 2,769 men and 997 women died. Suicide accounted for 417 of the men's (15%) and 68 of the women's (6.8%) deaths. Hanging was the most frequent method of suicide for both. Compared with the general population, the increased rate of suicide deaths among male farmers was 28% in 2008 and 22% in 2009. This increased rate was particularly high among those aged 45-54 years (31%) and 55-64 years (47%) in 2008 (and in the 55-64-year-old group in 2009 (64%). Two specific types of farming activity were associated with increased suicide mortality rates in both 2008 and 2009: dairy cattle farming (SMR = 1.56 [95% CI: 1.09-2.15] and SMR=1.47 [95% CI: 1.01-2.04]) and beef cattle farming (SMR = 2.27 [95% CI: 1.59-3.10] and SMR = 1.57 [95% CI: 1.01-2.27]). These results may be useful for a better understanding of the situation from an epidemiological standpoint and for improving suicide prevention policies in this particular population. PMID- 27409005 TI - Numerical analysis of double chirp effect in tapered and linearly chirped fiber Bragg gratings. AB - In this paper, a theoretical analysis of recently developed tapered chirped fiber Bragg gratings (TCFBG) written in co-directional and counter-directional configurations is presented. In particular, the effects of the synthesis of chirps resulting from both a fused taper profile and a linearly chirped fringe pattern of the induced refractive index changes within the fiber core are extensively examined. For this purpose, a numerical model based on the transfer matrix method (TMM) and the coupled mode theory (CMT) was developed for such a grating. The impact of TCFBG parameters, such as grating length and steepness of the taper transition, as well as the effect of the fringe pattern chirp rate on the spectral properties of the resulting gratings, are presented. Results show that, by using the appropriate design process, TCFBGs with reduced or enhanced resulting chirp, and thus with widely tailored spectral responses, can be easily achieved. In turn, it reveals a great potential application of such structures. The presented numerical approach provides an excellent tool for TCFBG design. PMID- 27409003 TI - G80A Single Nucleotide Polymorphism in Reduced Folate Carrier-1 Gene in a Mexican Population and its Impact on Survival in Patients with Acute Lymphoblastic Leukemia. AB - BACKGROUND: Hyper-CVAD is the treatment for patients with acute lymphoblastic leukemia in our institution. OBJECTIVE: To evaluate the impact of single nucleotide polymorphisms at genes associated with methotrexate metabolism on survival. METHODS: The presence of the single nucleotide polymorphisms G80A at reduced folate carrier-1 gene and C677T in the methylenetetrahydrofolate reductase gene was determined by denaturing high performance liquid chromatography and validated by sequencing. Both single nucleotide polymorphisms were evaluated in 71 healthy donors and in an exploratory pilot trial with acute lymphoblastic leukemia patients to determine the influence of these single nucleotide polymorphisms on clinical outcome. Clinical characteristics, response, and outcome were registered. A Cox regression analysis was done to evaluate factors influencing response and overall survival. RESULTS: There were no differences in the frequency of single nucleotide polymorphisms between volunteers and acute lymphoblastic leukemia patients according to the Hardy Weinberg test. Sensitivity and specificity were 72 and 91% for the G80A, and 64 and 75% for the C677T, respectively. The multivariate analysis showed that the T immunophenotype and the presence of single nucleotide polymorphism G80A reduced folate carrier-1 were associated with a shorter relapse-free survival and overall survival. CONCLUSIONS: The presence of G80A single nucleotide polymorphism at reduced folate carrier-1 gene in acute lymphoblastic leukemia patients was associated with a poorer prognosis. PMID- 27409006 TI - Self-homodyne free-space optical communication system based on orthogonally polarized binary phase shift keying. AB - A self-homodyne laser communication system based on orthogonally polarized binary phase shift keying is demonstrated. The working principles of this method and the structure of a transceiver are described using theoretical calculations. Moreover, the signal-to-noise ratio, sensitivity, and bit error rate are analyzed for the amplifier-noise-limited case. The reported experiment validates the feasibility of the proposed method and demonstrates its advantageous sensitivity as a self-homodyne communication system. PMID- 27409007 TI - Toward a mid-infrared femtosecond laser system with suspended-core tungstate tellurite glass fibers. AB - A simple design of a fiber laser system for generating high-quality pulses with a duration of order 100 fs with ultrabroad wavelength tunability in the 2-5 MUm range is discussed. This design incorporates conventional fs near-IR lasers and specially developed tungstate-tellurite fibers with two zero-dispersion wavelengths (ZDW) and relies on nonlinear wavelength conversion via either soliton self-frequency shift (SSFS) or red-shifted dispersive wave (DW) generation. The fiber parameters needed for such optical conversion have been scanned numerically and showed a possibility of SSFS beyond 4 MUm and of DW generation beyond 5 MUm. We have also studied and prepared tungstate-tellurite glasses and preforms that are highly stable against crystallization, exhibit extremely low level of hydroxyl groups absorption, and from which the suspended core two-ZDW fibers can be manufactured. PMID- 27409008 TI - Two-dimensional analytical modeling of a linear variable filter for spectral order sorting. AB - A two-dimensional thin film thickness model based on the geometry of a commercial coater which can calculate more effectively the profiles of linear variable filters (LVFs) has been developed. This is done by isolating the substrate plane as an independent coordinate (local coordinate), while the rotation and translation matrices are used to establish the coordinate transformation and combine the characteristic vector with the step function to build a borderline which can conclude whether the local mask will block the deposition or not. The height of the local mask has been increased up to 40 mm in the proposed model, and two-dimensional simulations are developed to obtain a thin film profile deposition on the substrate inside the evaporation chamber to achieve the specific request of producing a LVF zone width in a more economical way than previously reported [Opt. Express23, 5102 (2015)OPEXFF1094 408710.1364/OE.23.005102]. PMID- 27409009 TI - Fused fiber micro-knots. AB - We present fusing of a fiber micro-knot by a CO2 laser beam. We demonstrate tuning of the coupling strength and tuning of the spectral resonance of the micro-knot by the fusing process. The experimental results reveal that fusing the fiber micro-knots increases the coupling efficiency and improves the robustness and the stability of the micro-knots. PMID- 27409010 TI - Anisotropic acousto-optic interaction in tellurium crystal with acoustic walk off. AB - The influence of the acoustic beam energy walk-off on characteristics of anisotropic Bragg diffraction of light is studied theoretically by the example of a tellurium single crystal. Calculations for wide ranges of Bragg angles and ultrasound frequencies are produced on the basis of an original solution of the acousto-optic (AO) interaction problem, which takes into consideration the acoustic walk-off. It is established that the walk-off can substantially change the region of AO interaction, resulting in narrowing or broadening of the frequency characteristic depending on the crystal cut, acoustic frequency, incident light polarization, and walk-off angle sign. PMID- 27409011 TI - General construction method for a rotationally symmetric ultrashort distance catadioptric projector. AB - In this work, the off-axis imaging of a fan of rays with a rotationally symmetric mirror is studied, based on which a general construction method is proposed for the design of a rotationally symmetric ultrashort distance catadioptric projector. With the proposed method, the intermediate images at arbitrary planes of incidence can be obtained, and thus the designer has the freedom to choose suitable intermediate images to simplify the aberration correction of the catadioptric starting point. To prove the effectiveness of the proposed method, the construction process of a convex-type ultrashort distance catadioptric projector is presented. The intermediate image at the meridional plane is discontinuous, and the image distances for some fields are infinite. In contrast, the intermediate image at the sagittal plane is continuous, smooth, and finite and thus is selected to correct the skew aberrations in the catadioptric starting point. An initial configuration, which has small aberrations, is obtained without increasing the system complexity. Further automatic optimization is applied to the initial configuration to get the optimal solution. The simulated performance of the optimal solution is excellent. PMID- 27409012 TI - Laser confocal radius measurement method for unpolished spheres. AB - A laser confocal radius measurement method for unpolished spheres (CRMUS) is proposed for measuring the radius of an unpolished sphere during optical sphere processing. CRMUS uses the laser confocal focusing technique to accurately identify the cat's eye and confocal positions of the unpolished sphere, and then uses the distance between the cat's eye and confocal positions measured by a distance measurement interferometer to derive the radius. The partially coherent optical theoretical model of the CRMUS derived indicates that the CRMUS is able to measure the radius of the unpolished sphere with a roughness of less than 0.15 MUm. Using an unpolished sphere made of Schott BK7 as the test sphere, experimental results indicate that the CRMUS has a relative expanded uncertainty of less than 20 ppm. The CRMUS could greatly increase processing efficiency. PMID- 27409013 TI - Supercontinuum based absorption spectrometer for cycle-resolved multiparameter measurements in a rapid compression machine. AB - A broadband supercontinuum (SC) based absorption spectrometer capable of cycle resolved multiparameter measurements at internal combustion (IC) engine conditions is presented. Three parameters, temperature, pressure and water mole fraction, were extracted from broadband near-infrared H2O absorption spectra, spanning the wavelength-range from 1340 to 1405.5 nm, which exhibits a large number of specific H2O transitions. The spectrometer is based on spatial domain detection and features a near-infrared line scan camera as a detector. Measurements were performed during a compression cycle of a rapid compression machine comprising a pressure and temperature range from 2.5 to 65 bar and 300 to 900 K, respectively. With the new spectrometer, we are for the first time, based on the authors' knowledge, able to perform measurements based on SC radiation over a complete compression and expansion stroke at measurement rates up to 50 kHz. A detailed overview is provided about the best match algorithm between theory and experiments, including parameters from two different spectral databases, namely the Barber-Tennyson database (BT2) and HITRAN2012. The results indicate that spectral broadening effects are not properly described by theory, especially at pressure levels exceeding 20 bar, which culminates in a clear underestimation of the derived pressure data by SC absorption spectroscopy. Nevertheless, temperature can be determined accurately by performing a three parameter fit based on water mole fraction, temperature, and pressure. In contrast, making use of pressure transducer data as look-up values and varying only temperature and H2O mole fraction to find the best match leads to a clear overestimation of temperature at elevated pressures. PMID- 27409014 TI - Characterization of prospective explosive materials using terahertz time-domain spectroscopy. AB - We investigated six prospective explosive materials in the terahertz range using time-domain spectroscopy. A family of energetic azotetrazolate salts and two caged nitramines were studied. A number of distinct spectral features were observed in the 0.8-3.2 THz frequency range. In transmission configuration in ambient temperature, we determined the absorption coefficient and the refractive index of the materials, which were compressed as pellets. Because the visibility of some absorption peaks was not clear, additionally we performed characterization of these materials in a temperature range from -175 degrees C to 0 degrees C, which resulted in highlighting peaks with low amplitude. Because the considered explosives are insensitive to compression, we also measured them using an attenuated total reflection (ATR) technique, in which sample preparation is easier than with pressed pellets. The absorption peaks measured by ATR agree well with those determined in transmission. This suggests that ATR also can be used for identification of these classes of materials. PMID- 27409015 TI - Q-switched fiber laser based on an acousto-optic modulator with injection seeding technique. AB - The operation mechanism and the pulse property of an actively Q-switched erbium doped fiber laser based on an acousto-optic modulator (AOM) switch with the injection seeding technique are investigated. Our results show that the Q switched pulses can be locked to oscillate near a fixed frequency higher than that of the seed laser, though the frequency-shift effect of the AOM impedes stable cavity mode oscillations. The operation mechanism of such Q-switch fiber lasers can be explained by the mutual locking-in among the shifted frequency components originated from the injected coherence seed with the help of the gain dynamics of the Q-switch cavity. Moreover, narrow-linewidth Q-switched pulses with different repetition rates can be obtained with different cavity lengths for incredibly stable output pulses without any use of cavity-stabilized techniques. PMID- 27409016 TI - Loop gain stabilizing with an all-digital automatic-gain-control method for high precision fiber-optic gyroscope. AB - For a fiber-optic gyroscope (FOG) using electronic dithers to suppress the dead zone, without a fixed loop gain, the deterministic compensation for the dither signals in the control loop of the FOG cannot remain accurate, resulting in the dither residuals in the FOG rotation rate output and the navigation errors in the inertial navigation system. An all-digital automatic-gain-control method for stabilizing the loop gain of the FOG is proposed. By using a perturbation square wave to measure the loop gain of the FOG and adding an automatic gain control loop in the conventional control loop of the FOG, we successfully obtain the actual loop gain and make the loop gain converge to the reference value. The experimental results show that in the case of 20% variation in the loop gain, the dither residuals are successfully eliminated and the standard deviation of the FOG sampling outputs is decreased from 2.00 deg/h to 0.62 deg/h (sampling period 2.5 ms, 10 points smoothing). With this method, the loop gain of the FOG can be stabilized over the operation temperature range and in the long-time application, which provides a solid foundation for the engineering applications of the high-precision FOG. PMID- 27409017 TI - Ptychography for optical metrology with limited translation knowledge. AB - We introduce unknown-transverse translation diversity phase retrieval: a ptychographic algorithm for optical metrology when a subaperture is translating through a plane conjugate to the exit pupil in a very poorly known fashion. The algorithm estimates the direction of translation and the distance traveled by the subaperture from one point spread function (PSF) to the next. It also estimates unknown point target motion and rotations of the subaperture between PSF acquisitions from the PSF data. PMID- 27409018 TI - Phase gradient algorithm method for three-dimensional holographic ladar imaging. AB - Three-dimensional (3D) holographic ladar uses digital holography with frequency diversity to add the ability to resolve targets in range. A key challenge is that since individual frequency samples are not recorded simultaneously, differential phase aberrations may exist between them, making it difficult to achieve range compression. We describe steps specific to this modality so that phase gradient algorithms (PGA) can be applied to 3D holographic ladar data for phase corrections across multiple temporal frequency samples. Substantial improvement of range compression is demonstrated with a laboratory experiment where our modified PGA technique is applied. Additionally, the PGA estimator is demonstrated to be efficient for this application, and the maximum entropy saturation behavior of the estimator is analytically described. PMID- 27409019 TI - Region-confined restoration method for motion-blurred star image of the star sensor under dynamic conditions. AB - Under dynamic conditions, the centroiding accuracy of the motion-blurred star image decreases and the number of identified stars reduces, which leads to the degradation of the attitude accuracy of the star sensor. To improve the attitude accuracy, a region-confined restoration method, which concentrates on the noise removal and signal to noise ratio (SNR) improvement of the motion-blurred star images, is proposed for the star sensor under dynamic conditions. A multi-seed region growing technique with the kinematic recursive model for star image motion is given to find the star image regions and to remove the noise. Subsequently, a restoration strategy is employed in the extracted regions, taking the time consumption and SNR improvement into consideration simultaneously. Simulation results indicate that the region-confined restoration method is effective in removing noise and improving the centroiding accuracy. The identification rate and the average number of identified stars in the experiments verify the advantages of the region-confined restoration method. PMID- 27409020 TI - Convex optimization-based windowed Fourier filtering with multiple windows for wrapped-phase denoising. AB - The windowed Fourier filtering (WFF), defined as a thresholding operation in the windowed Fourier transform (WFT) domain, is a successful method for denoising a phase map and analyzing a fringe pattern. However, it has some shortcomings, such as extremely high redundancy, which results in high computational cost, and difficulty in selecting an appropriate window size. In this paper, an extension of WFF for denoising a wrapped-phase map is proposed. It is formulated as a convex optimization problem using Gabor frames instead of WFT. Two Gabor frames with differently sized windows are used simultaneously so that the above mentioned issues are resolved. In addition, a differential operator is combined with a Gabor frame in order to preserve discontinuity of the underlying phase map better. Some numerical experiments demonstrate that the proposed method is able to reconstruct a wrapped-phase map, even for a severely contaminated situation. PMID- 27409021 TI - Propagation of an optical vortex carried by a partially coherent Laguerre Gaussian beam in turbulent ocean. AB - The analytical formulas for the orbital angular momentum (OAM) mode probability density, signal OAM mode detection probability, and spiral spectrum of partially coherent Laguerre-Gaussian (LG) beams with optical vortices propagation in weak horizontal oceanic turbulent channels were developed, based on the Rytov approximation theory. The effect of oceanic turbulence and beam source parameters on the propagation behavior of the optical vortices carried by partially coherent LG beams was investigated in detail. Our results indicated that optical turbulence in an ocean environment produced a much stronger effect on the optical vortex than that in an atmosphere environment; the effective range of the signal OAM mode of LG beams with a smaller ratio of the mode crosstalk was limited to only several tens of meters in turbulent ocean. The existence of oceanic turbulence evidently induced OAM mode crosstalk and spiral spectrum spread. The effects of oceanic turbulence on the OAM mode detection probability increased with the increase of radial and azimuthal mode orders, oceanic turbulent equivalent temperature structure parameter, and temperature-salinity balance parameter. The spatial partial coherence of the beam source would enhance the effect of turbulent aberrations on the signal OAM mode detection probability, and fully coherent vortex beams provided better performance than partially coherent ones. Increasing wavelength of the vortex beams would help improve the performance of this quantum optical communication system. These results might be of interest for the potential application of optical vortices in practical underwater quantum optical communication among divers, submarines, and sensors in the ocean environment. PMID- 27409022 TI - Performance analysis of fiber-based free-space optical communications with coherent detection spatial diversity. AB - The performances of fiber-based free-space optical (FSO) communications over gamma-gamma distributed turbulence are studied for multiple aperture receiver systems. The equal gain combining (EGC) technique is considered as a practical scheme to mitigate the atmospheric turbulence. Bit error rate (BER) performances for binary-phase-shift-keying-modulated coherent detection fiber-based free-space optical communications are derived and analyzed for EGC diversity receptions through an approximation method. To show the net diversity gain of a multiple aperture receiver system, BER performances of EGC are compared with a single monolithic aperture receiver system with the same total aperture area (same average total incident optical power on the aperture surface) for fiber-based free-space optical communications. The analytical results are verified by Monte Carlo simulations. System performances are also compared for EGC diversity coherent FSO communications with or without considering fiber-coupling efficiencies. PMID- 27409023 TI - Lidar measurements of solid rocket propellant fire particle plumes. AB - This paper presents the first, to our knowledge, direct measurement of aerosol produced by an aluminized solid rocket propellant (SRP) fire on the ground. Such fires produce aluminum oxide particles small enough to loft high into the atmosphere and disperse over a wide area. These results can be applied to spacecraft launchpad accidents that expose spacecraft to such fires; during these fires, there is concern that some of the plutonium from the spacecraft power system will be carried with the aerosols. Accident-related lofting of this material would be the net result of many contributing processes that are currently being evaluated. To resolve the complexity of fire processes, a self consistent model of the ground-level and upper-level parts of the plume was determined by merging ground-level optical measurements of the fire with lidar measurements of the aerosol plume at height during a series of SRP fire tests that simulated propellant fire accident scenarios. On the basis of the measurements and model results, the Johns Hopkins University Applied Physics Laboratory (JHU/APL) team was able to estimate the amount of aluminum oxide (alumina) lofted into the atmosphere above the fire. The quantification of this ratio is critical for a complete understanding of accident scenarios, because contaminants are transported through the plume. This paper provides an estimate for the mass of alumina lofted into the air. PMID- 27409024 TI - Using maximum spectrum of continuous wavelet transform for demodulation of an overlapped spectrum in a fiber Bragg grating sensor network. AB - The maximum spectrum of the continuous wavelet transform (MSCWT) is proposed to demodulate the central wavelengths for the overlapped spectrum in a serial fiber Bragg grating (FBG) sensing system. We describe the operation principle of the MSCWT method. Moreover, the influence of the interval gap between two FBG wavelengths, 3 dB bandwidths, and optical powers of the reflected spectra are discussed. The simulation and experimental results indicate that the MSCWT can resolve an overlapped spectrum and decode the central wavelength with high accuracy. More importantly, the proposed peak detection method can enhance the sensing capacity of a wavelength division multiplexing FBG sensor network. PMID- 27409025 TI - Refractive index gratings in electro-optic polymer thin films. AB - Refractive index gratings have been inscribed in polymer thin films by permanently photobleaching the organic chromophore PYR-3 dopant. The grating inscription process was investigated in detail for the purpose of improving the diffraction efficiency (eta) of the PYR-3 doped polymer gratings. Three processes were identified that contributed to the eta of the first diffracted order: a periodic change in the refractive index due to photobleaching of the PYR-3, formation of the surface relief grating as a consequence of free volume change during bleaching, and the introduction of periodic, strain-induced changes in the refractive index. PMID- 27409026 TI - Thin film multilayer filters for solar EUV telescopes. AB - Al, with a passband in the wavelength range of 17-60 nm, and Zr, with a passband in the wavelength range of 6.5-17 nm, thin films on a support grid or support membrane are frequently used as UV, visible, and near-IR blocking filters in solar observatories. Although they possess acceptable optical performance, these filters also have some shortcomings such as low mechanical strength and low resistance to oxidation. These shortcomings hinder meeting the requirements for filters of future telescopes. We propose multilayer thin film filters on the basis of Al, Zr, and other materials with improved characteristics. It was demonstrated that stretched multilayer films on a support grid with a mesh size up to 5 mm can withstand vibration loads occurring during spacecraft launch. A large mesh size is preferable for filters of high-resolution solar telescopes, since it allows image distortion caused by light diffraction on the support grid to be avoided. We have investigated the thermal stability of Al/Si and Zr/Si multilayers assuming their possible application as filters in the Intergelioprobe project, in which the observation of coronal plasma will take place close to the Sun. Zr/Si films show high thermal stability and may be used as blocking filters in the wavelength range of 12.5-17 nm. Al/Si films show lower thermal stability: a significant decrease in the film's transmission in the EUV spectral range and an increase in the visible spectrum have been observed. We suppose that the low thermal stability of Al/Si films restricts their application in the Intergelioprobe project. Thus, there is a lack of filters for the wavelength range of lambda>17 nm. Be/Si and Cr/Si filters have been proposed for the wavelength range near 30.4 nm. Although these filters have lower transparency than Al/Si, they are superior in thermal stability. Multilayer Sc/Al filters with relatively high transmission at a wavelength of 58.4 nm (HeI line) and simultaneously sufficient rejection in the wavelength range near 30.4 nm (HeII line) have been fabricated. They are planned to be used in the project KORTES, whose telescopes will have an EUV channel at 58.4 nm. PMID- 27409027 TI - Boundary condition thermometry using a thermographic-phosphor-coated thin filament. AB - Thermographic phosphors (TPs) exhibit a temperature sensitive emission spectrum when excited with ultraviolet radiation. In this study, 14 MUm diameter SiC fibers are coated with ZnO or Dy:YAG using a ceramic binder to a total diameter of 70+/-9 MUm. ZnO and Dy:YAG fibers were used to measure fiber temperatures in the range of 294-450 K and 450-1245 K, respectively. The coated fiber provides higher signal levels compared to TP particle seeding and is no more invasive than the commonly used thermocouple. A calibration is performed to relate fiber temperature to the ratio of luminescent signal collected within two different bands of the fiber emission spectrum. Temperature was measured along the inlet of a series of nitrogen diluted ethylene diffusion flames stabilized on the Yale coflow burner to determine suitable thermal boundary conditions for computational modeling. The boundary condition temperatures were derived from a spline fitting of data acquired from the two fiber types in order to obtain fiber temperature sensitivity from 294 to 1245 K. The peak near-burner temperature was found to be higher than ambient conditions and to increase and shift its location radially outward with increased fuel percentage. PMID- 27409028 TI - Simple parametric model for intensity calibration of Cassini composite infrared spectrometer data. AB - Accurate intensity calibration of a linear Fourier-transform spectrometer typically requires the unknown science target and the two calibration targets to be acquired under identical conditions. We present a simple model suitable for vector calibration that enables accurate calibration via adjustments of measured spectral amplitudes and phases when these three targets are recorded at different detector or optics temperatures. Our model makes calibration more accurate both by minimizing biases due to changing instrument temperatures that are always present at some level and by decreasing estimate variance through incorporating larger averages of science and calibration interferogram scans. PMID- 27409029 TI - Characterization of drying paint coatings by dynamic speckle and holographic interferometry measurements. AB - In this work we implemented dynamic speckle and holographic interferometry techniques to characterize the drying process of solvent-based paint coatings. We propose a simple way to estimate drying time by measuring speckle activity and incrementally fitting experimental data through standard regression algorithms. This allowed us to predict drying time after about 20-30 min of paint application, which is fast compared to usual times required to reach the so called tack-free state (~2 h). In turn, we used holographic interferometry to map small thickness variations in the coating surface during drying. We also demonstrate that results obtained from both techniques correlate with each other, which allows us to improve the accuracy of the drying time estimation. PMID- 27409030 TI - Experimental capabilities of 0.4 PW, 1 shot/min Scarlet laser facility for high energy density science. AB - We report on the recently completed 400 TW upgrade to the Scarlet laser at The Ohio State University. Scarlet is a Ti:sapphire-based ultrashort pulse system that delivers >10 J in 30 fs pulses to a 2 MUm full width at half-maximum focal spot, resulting in intensities exceeding 5*1021 W/cm2. The laser fires at a repetition rate of once per minute and is equipped with a suite of on-demand and on-shot diagnostics detailed here, allowing for rapid collection of experimental statistics. As part of the upgrade, the entire laser system has been redesigned to facilitate consistent, characterized high intensity data collection at high repetition rates. The design and functionality of the laser and target chambers are described along with initial data from commissioning experimental shots. PMID- 27409031 TI - Phase-retrieval-based attacks on linear-canonical-transform-based DRPE systems. AB - The hybrid input-output algorithm, error reduction algorithm, and combinations of both phase retrieval algorithms are applied to perform ciphertext-only attacks on linear canonical transform (LCT)-based amplitude encoding double-random-phase encryption (DRPE) systems. Special cases of LCT-based DRPE systems, i.e., Fourier transform-based, fractional-Fourier-transform-based, and Fresnel-transform-based DRPE, can also be successfully attacked using the method proposed. Numerical simulations are performed to demonstrate the efficacy of the proposed attacking method. PMID- 27409032 TI - 360 deg full-parallax light-field display using panoramic camera. AB - One of the common approaches to achieving vertical parallax for the horizontal parallax-only light-field display is to introduce the viewer-tracking method. A panoramic camera is assembled in a 360 deg scanning light-field display system for the full-parallax demand in this study, wherein the image generation algorithm is improved to be sensitive to multiple viewer positions, and the tracking and rendering are processed in real time. The horizontal-parallax-only light-field display using a panoramic camera is determined to be able to achieve smooth and consecutive full-parallax performance for multiple viewers in a 360 deg range. PMID- 27409033 TI - Amplified spontaneous emission from DCJTB encapsulated in mesostructured composite silica SBA-15. AB - Amplified spontaneous emission (ASE) characteristics of a red dye 4 (Dicyanomethylene)-2-t-butyl-6-(1,1,7,7- etramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) encapsulated in a highly ordered mesoporous SBA-15 were studied. The mesoporous composite silica film loaded with organic dye has been successfully synthesized by a solgel reaction process and a simple postgrafting method at room temperature. The spectrum narrowing phenomena has been observed when the composite film is pumped at lambdap=532 nm by a Nd:YAG ed laser. There is a substantial reduction in the full width at half-maximum of the emitting light, which is one of the signatures of the presence of ASE. The ASE threshold and net gain, respectively, reached 0.03 mJ pulse-1 and 34.7 cm-1 for the DCJTB encapsulated in mesoporous SBA-15 film. The optimized ASE properties owe much to the effects of the better spatial confinement of the molecules in the ordered mesoporous structure of the host SBA-15. PMID- 27409034 TI - Aero-optical effects of an optical seeker with a supersonic jet for hypersonic vehicles in near space. AB - The aero-optical effects of an optical seeker with a supersonic jet for hypersonic vehicles in near space were investigated by three suites of cases, in which the altitude, angle of attack, and Mach number were varied in a large range. The direct simulation Monte Carlo based on the Boltzmann equation was used for flow computations and the ray-tracing method was used to simulate beam transmission through the nonuniform flow field over the optical window. Both imaging displacement and phase deviation were proposed as evaluation parameters, and along with Strehl ratio they were used to quantitatively evaluate aero optical effects. The results show that aero-optical effects are quite weak when the altitude is greater than 30 km, the imaging displacement is related to the incident angle of a beam, and it is minimal when the incident angle is approximately 15 degrees . For reducing the aero-optical effects, the optimal location of an aperture should be in the middle of the optical window. PMID- 27409035 TI - Analysis and improvement of accuracy, sensitivity, and resolution of the coherent gradient sensing method. AB - The coherent gradient sensing (CGS) method, one kind of shear interferometry sensitive to surface slope, has been applied to full-field curvature measuring for decades. However, its accuracy, sensitivity, and resolution have not been studied clearly. In this paper, we analyze the accuracy, sensitivity, and resolution for the CGS method based on the derivation of its working principle. The results show that the sensitivity is related to the grating pitch and distance, and the accuracy and resolution are determined by the wavelength of the laser beam and the diameter of the reflected beam. The sensitivity is proportional to the ratio of grating distance to its pitch, while the accuracy will decline as this ratio increases. In addition, we demonstrate that using phase gratings as the shearing element can improve the interferogram and enhance accuracy, sensitivity, and resolution. The curvature of a spherical reflector is measured by CGS with Ronchi gratings and phase gratings under different experimental parameters to illustrate this analysis. All of the results are quite helpful for CGS applications. PMID- 27409037 TI - Influence of gas humidity on the reflection coefficient of multilayer dielectric mirrors. AB - The influence of water vapor on the reflection coefficient of multilayer mirrors was studied using a gas cell with multiple reflections from the mirrors. A strong change in the reflection coefficient of the mirrors (up to 0.9%) was found when water vapor under a pressure of 23 mbar was injected into the cell, which was interpreted as a change in the refraction index of the layers of multilayer coatings when water vapor penetrated into the porous coating structure. PMID- 27409036 TI - Transition of lasing modes in polymeric opal photonic crystal resonating cavity. AB - We demonstrate the transition of lasing modes in the resonating cavity constructed by polystyrene opal photonic crystals and 7 wt. % tert-butyl Rhodamine B doped polymer film. Both single mode and multiple mode lasing emission are observed from the resonating cavity. The lasing threshold is determined to be 0.81 MUJ/pulse for single mode lasing emission and 2.25 MUJ/pulse for multiple mode lasing emission. The single mode lasing emission is attributed to photonic lasing resulting from the photonic bandgap effect of the opal photonic crystals, while the multiple mode lasing emission is assigned to random lasing due to the defects in the photonic crystals. The result would benefit the development of low threshold polymeric solid state photonic crystal lasers. PMID- 27409038 TI - Large radius of curvature measurement based on virtual quadratic Newton rings phase-shifting moire-fringes measurement method in a nonnull interferometer. AB - We have proposed a virtual quadratic Newton rings phase-shifting moire-fringes measurement method in a nonnull interferometer to measure the large radius of curvature for a spherical surface. In a quadratic polar coordinate system, linear carrier testing Newton rings interferogram and virtual Newton rings interferogram form the moire fringes. It is possible to retrieve the wavefront difference data between the testing and standard spherical surface from the moire fringes after low-pass filtering. Based on the wavefront difference data, we deduced a precise formula to calculate the radius of curvature in the quadratic polar coordinate system. We calculated the retrace error in the nonnull interferometer using the multi-configuration model of the nonnull interferometric system in ZEMAX. Our experimental results indicate that the measurement accuracy is better than 0.18% for a spherical mirror with a radius of curvature of 41,400 mm. PMID- 27409039 TI - Confusion: Submission of conference papers to Applied Optics: editorial. AB - Applied Optics Editor Ron Driggers explains the new policy for considering expanded conference papers in OSA journals. PMID- 27409040 TI - Impact of pulsed light on cellular activity of Salmonella enterica. AB - AIMS: The objective of this study was a comprehensive characterization of physiological changes of Salmonella enterica induced by intense broad spectrum pulsed light (PL). After exposing the bacteria to this nonthermal decontamination technology on a gel surface, multiple viability parameters beyond culturability were assessed. METHODS AND RESULTS: By applying flow cytometry, a luciferin luciferase bioluminescence assay and a microplate assay to measure the current redox activity, the impact of pulsed light on the membrane potential, membrane integrity, esterase activity, efflux pump activity, expression of the green fluorescent protein (GFP), respiration activity and ATP-content of Salm. enterica ATCC BAA-1045 was determined. These culture-independent methods for assessing the bacterial activity were compared to the ability to grow on tryptic soy agar. It is shown that this strain is rather sensitive to PL considering colony count reductions, while on the other hand unculturable bacteria still exhibit significant cellular energetic functions. However, this residual activity after PL exposure significantly decreases during sample storage in buffer for 24 h. This study also shows that the GFP expression of PL-treated cells which have rendered unculturable is severely reduced. CONCLUSIONS: This study reveals that although not all cellular functions of Salm. enterica are immediately shut down after PL exposure, the synthesis of new GFP is strongly reduced and affected to a similar extent as the culturability. SIGNIFICANCE AND IMPACT OF THE STUDY: It is shown for the first time, that even there is significant bacterial activity measurable after PL exposure, it is likely that nongrowing pathogenic bacteria like Salm. enterica are unable to express proteins, which is of great importance regarding their pathogenicity. PMID- 27409041 TI - Watchful Waiting for Cases of Pediatric Otitis Media: Modeling Parental Response to Physician Advice. AB - Watchful waiting (WW) can reduce unnecessary antibiotic use in the treatment of pediatric otitis media (ear infection), but its utility is impaired by underutilization and noncompliance. Guided by advice response theory, the current study proposes advantage and capacity as factors that predict how caregivers evaluate and respond affectively to WW. Parents (N = 373) of at least 1 child age 5 years or younger completed questionnaires that assessed responses to hypothetical WW advice for their youngest child. Perceptions of advantage from WW and the capacity to monitor and manage symptoms predicted advice quality, physician trust, and future compliance both directly and indirectly through negative affect. The findings suggest the elaboration of advice response theory to include more aspects of advice content evaluation (e.g., advantage) and the influence of negative affect. The study also provides practical guidance for physicians seeking to improve caregiver reception of WW advice. PMID- 27409042 TI - Influence of bicortical techniques in internal connection placed in premaxillary area by 3D finite element analysis. AB - The aim of study was to evaluate the stress distribution in implant-supported prostheses and peri-implant bone using internal hexagon (IH) implants in the premaxillary area, varying surgical techniques (conventional, bicortical and bicortical in association with nasal floor elevation), and loading directions (0 degrees , 30 degrees and 60 degrees ) by three-dimensional (3D) finite element analysis. Three models were designed with Invesalius, Rhinoceros 3D and Solidworks software. Each model contained a bone block of the premaxillary area including an implant (IH, O4 * 10 mm) supporting a metal-ceramic crown. 178 N was applied in different inclinations (0 degrees , 30 degrees , 60 degrees ). The results were analyzed by von Mises, maximum principal stress, microstrain and displacement maps including ANOVA statistical test for some situations. Von Mises maps of implant, screws and abutment showed increase of stress concentration as increased loading inclination. Bicortical techniques showed reduction in implant apical area and in the head of fixation screws. Bicortical techniques showed slight increase stress in cortical bone in the maximum principal stress and microstrain maps under 60 degrees loading. No differences in bone tissue regarding surgical techniques were observed. As conclusion, non-axial loads increased stress concentration in all maps. Bicortical techniques showed lower stress for implant and screw; however, there was slightly higher stress on cortical bone only under loads of higher inclinations (60 degrees ). PMID- 27409043 TI - Screening of biomethane production potential from dominant microalgae. AB - The use of microalgae for biomethane production has been considerably increasing during the recent years. In this study, four dominant species belonging to the genera Scenedesmus, Chlorella, Dunaliella and Nostoc were selected. The influence of different genera with several morphological, structural and physicochemical characteristics on methane production was assessed in biochemical methane potential (BMP) tests. The ultimate methane yield values were 332 +/- 24, 211 +/- 2, 63 +/- 17 and 28 +/- 10 mL CH4/g VSadded for Scenedesmus obliquus, Chlorella sorokiniana, Dunaliella salina and Nostoc sp., respectively. The highest methane production was achieved by microalga species that had no complex cell wall or wall basically composed by proteins and simple sugars such as in S. obliquus, whereas lower methane yields were found for D. salina and Nostoc sp., due to the salinity effects and cell wall composition in terms of complex polysaccharide and glycolipid layers, respectively. Kinetic constant values obtained in the BMP tests ranged between 1.00 +/- 0.08 and 0.097 +/- 0.005 days(-1) for D. salina and S. obliquus, respectively. PMID- 27409044 TI - Distinguishing computed tomography findings in patients with empty nose syndrome. AB - BACKGROUND: Given the lack of basic diagnostic criteria for empty nose syndrome (ENS), we sought to define whether consistent radiographic characteristics could be identified to aid in the development of such criteria. METHODS: Computed tomography (CT) scans were collected from 65 patients diagnosed with ENS, patients with a history of submucosal inferior turbinate reduction (ITR) without ENS, and patients without a history of sinonasal procedures. Measurements were taken at the level of the nasolacrimal duct, including the inferior turbinate (IT) mucosal thickness, and the widest distances between septum-IT, nasal floor IT, lateral nasal wall-IT, and septum-lateral nasal wall. The thickest sites of soft tissue density of the nasal cavity floor, septum, and lateral wall were also measured in the anterior, central, and posterior segments of the nasal cavity. RESULTS: The mucosal thickness of both the central and posterior segments of the septum in ENS subjects was significant when compared to ITR without ENS (p < 0.01) and control subjects (p < 0.01). Constant landmarks such as the agger nasi, the presence of middle turbinate, and the nasolacrimal duct defined a simple set of landmarks that can serve as the start of the central-nasal region, and a cutoff >2.64 mm and >1.32 mm in the central nasal and posterior nasal regions provided the highest likelihood of differentiating ENS patients from ITR without ENS patients. CONCLUSION: These findings provide evidence there are 2 objective radiographic changes (central and posterior septal mucosa) that suggest ENS patients can be discriminated based on mucosal CT findings. PMID- 27409047 TI - The Witches of Macbeth. PMID- 27409048 TI - The Toxic Touch-Cutaneous Poisoning in Classics and Shakespeare. PMID- 27409049 TI - The Leper King. PMID- 27409050 TI - Flower Power-The Versatility of Bloodroot. PMID- 27409051 TI - The Golden Ratio of Beauty-A Hidden Treasure. PMID- 27409052 TI - Confirmatory Testing for Onychomycosis. PMID- 27409053 TI - Confirmatory Testing for Onychomycosis. PMID- 27409054 TI - Confirmatory Testing for Onychomycosis-Reply. PMID- 27409055 TI - Saint Anthony's Fire. PMID- 27409056 TI - Hypoxia-induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia inducible factors-1alpha protein. AB - BACKGROUND: Hypoxia is the most important stimulus leading to up-regulation of vascular endothelial growth factor (VEGF) in the retina via elevation of hypoxia inducible factors-1alpha (HIF-1alpha) protein. The purpose of this study was to test the effects of melatonin on the expression of VEGF and HIF-1alpha in the cultured human retinal pigment epithelial (RPE) cells under normoxia and hypoxia. METHOD: An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2 ) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without melatonin under normoxia and hypoxia. The protein and RNA levels of VEGF and HIF-1alpha were measured by ELISA kits and RT-PCR, respectively. RESULT: Hypoxia induced a significant increase of expression and secretion of VEGF and accumulation of HIF-1alpha protein in RPE cells (P < 0.05). Melatonin at 10-5 to 10-8 M significantly inhibited hypoxia-induced expression, the secretion of VEGF and the accumulation of HIF-1alpha protein (P < 0.05), but not affected expression of VEGF and HIF-1alpha under normoxia (P > 0.05). CONCLUSION: This study suggests that melatonin may have potential value in the prevention and treatment of various retinal diseases associated with increase of VEGF, vascular leakage and angiogenesis. PMID- 27409057 TI - THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I ANDCLINICALLY UNCONTROLLED TYPE 2 DIABETES. AB - INTRODUCTION : Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. OBJECTIVE : To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. METHOD : Research was conducted in PubMed, Medline, PubMed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetesmellitus. In addition, representatives of the societiesinvolved, as an expert panel, issued opinions. RESULTS : Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMI<35 kg/m2; Safety of metabolic surgery in patients with BMI<35 kg/m2; Long-term effects of surgery in patients with baseline BMI<35 kg/m2 and Proposal for a Metabolic Risk Score. CONCLUSION : Metabolic surgery has well-defined mechanisms of action both in experimental and human studies. Gastrointestinal interventions in T2DM patients with IMC<=35 kg/m2 has similar safety and efficacy when compared to groups with greater BMIs, leading to the improvement of diabetes in a superior manner than clinical treatment and lifestyle changes, in part through weight loss independent mechanisms . There is no correlation between baseline BMI and weight loss in the long term with the success rate after any surgical treatment. Gastrointestinal surgery treatment may be an option for patients with T2DM without adequate clinical control, with a BMI between 30 and 35, after thorough evaluation following the parameters detailed in Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. INTRODUCAO: Mesmo considerando o avanco do tratamento clinico ocorrido nos ultimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda sao desanimadores quanto ao controle da obesidade e da diabete melito tipo 2(DMT2),com grande parcela de doentes em tratamento clinico ficando fora da meta desejada de controle. OBJETIVO: Apresentar proposta de Escore de Risco Metabolico para melhor orientar a indicacao cirurgica do diabete em pacientes com indice de massa corporea (IMC) mais baixo nos quais o uso de procedimento cirurgico para obesidade ainda e controverso. METODO: Foi realizada pesquisa nas bases de dados PubMed, Medline, PubMed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabolica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opinioes em pontos nos quais nao existia na literatura trabalhos com graus de evidencia elevados. RESULTADOS: Foram encontrados 45 artigos relacionadosque foram analisados pelos criterios da medicina baseada em evidencias.As opinioes agrupadas procuraram responder as seguintes questoes: Porque cirurgia metabolica e nao bariatrica?;Mecanismos envolvidos no controle glicemico; IMC como criterio isolado de indicacao cirurgica para o DMT2 nao controlado; Resultados de estudos de cirurgia metabolica em IMC<35 kg/m2; Seguranca da cirurgia metabolica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabolico. CONCLUSAO: A cirurgia metabolica tem mecanismos de acao bem definidos tanto em estudos experimentais quanto em seres humanos. As intervencoes gastrointestinais em diabeticos com IMC<=35 kg/m2 possuem seguranca e eficacia semelhantes aos grupos com IMCs maiores, levando a melhora do diabete de forma superior aos tratamentos clinicos e mudancas de estilo de vida, em parte atraves de mecanismos independentes da perda ponderal. Nao ha correlacao entre o IMC inicial e perda ponderal em longo prazo com os indices de sucesso do tratamento cirurgico. O tratamento cirurgico e opcao para os pacientes portadores de DMT2 sem adequado controle clinico, com IMC entre 30 e 35, apos minuciosa avaliacao seguindo os parametros dispostos no Escore de Risco Metabolico aqui proposto. DGYR e a tecnica indicada para os pacientes selecionados no Escore, existindo a possibilidade de indicacao da gastrectomia vertical para os casos em que exista contraindicacao para ela. O paciente deve ser avaliado por equipe multiprofissional envolvida na indicacao, preparo e acompanhamento apos as operacoes e acompanhados com monitorizacao de complicacoes micro e macrovasculares. PMID- 27409058 TI - Retrograde Transpedal Access for Revascularization of Below-the-Knee Arteries in Patients with Critical Limb Ischemia after an Unsuccessful Antegrade Transfemoral Approach. AB - PURPOSE: To evaluate the safety and technical and clinical success of endovascular below-the-knee (BTK) artery revascularization by a retrograde transpedal access. MATERIALS AND METHODS: We retrospectively identified 16/172 patients (9.3 %) with endovascular BTK revascularization in whom a transfemoral approach had failed and transpedal access had been attempted. The dorsal pedal (n = 13) or posterior tibial (n = 3) artery was accessed using a dedicated access set and ultrasound guidance. The procedure was finished in antegrade fashion by plain old balloon angioplasty (POBA). Comorbidities, vessel diameter and calcification at the access site were recorded. The analyzed outcomes were technical success, procedural complications, procedure time, crossing (guidewire beyond lesion and intra-luminal) and procedural (residual stenosis < 30 % after POBA) success, and limb salvage. RESULTS: Diabetes, coronary artery disease and hypertension were present in 15 patients (93.8 %), and both renal impairment and previous amputations in 7 (43.8 %). Pedal access vessel calcification was present in 5/16 patients (31.3 %). The mean diameter was 1.75 +/-0.24 mm. The procedure time was 92.4 +/-23 min. The success rate for achieving retrograde access was 100 %. Retrograde crossing was successful in 12/16 patients (75.0 %). Procedural success was observed in 10/16 patients (68.8 %). Minor complications occurred in 2/16 patients (12.5 %). The rate of limb salvage was 72.9 %, and the overall survival was 100 % at 12 months. Major amputations after revascularization occurred in 2/16 patients (12.5 %). CONCLUSION: If an antegrade transfemoral approach to BTK lesions fails, a retrograde transpedal approach may nevertheless facilitate treatment. This approach appears to be safe and offers high technical and acceptable clinical success rates. KEY POINTS: * Retrograde approaches via transpedal or transtibial vessels are safe and offer high technical success.* One problem after technically successful puncture might be the re-entry following subintimal retrograde lesion crossing.* After a failed attempt at antegrade revascularization of a BTK occlusion, a retrograde approach should be performed. Citation Format: * Goltz JP, Planert M, Horn M et al. Retrograde Transpedal Access for Revascularization of Below-the-Knee Arteries in Patients with Critical Limb Ischemia after an Unsuccessful Antegrade Transfemoral Approach. Fortschr Rontgenstr 2016; 188: 940 - 948. PMID- 27409059 TI - [Not Available]. PMID- 27409060 TI - [Not Available]. PMID- 27409061 TI - [Not Available]. PMID- 27409062 TI - ? PMID- 27409063 TI - Rehabilitative intervention during and after pediatric hematopoietic stem cell transplantation: An analysis of the existing literature. AB - Hematopoietic stem cell transplantation is a therapeutic strategy for several oncohematological diseases. It increases survival rates but leads to a high incidence of related effects. The objective of this paper was to examine the existing literature on physical exercise interventions among pediatric HSCT recipients to explore the most often utilized rehabilitative assessment and treatment tools. Studies published from 2002 to April 1, 2015 were selected: 10 studies were included. A previous literary review has shown that rehabilitation programs have a positive impact on quality of life. Our analysis identified some significant outcome variables and shared intervention areas. PMID- 27409064 TI - Erratum. AB - [This corrects the article doi: 10.1590/1518-8345.0995.2679] [This corrects the article doi: 10.1590/1518-8345.1082.2669] [This corrects the article doi: 10.1590/1518-8345.1069.2672] [This corrects the article doi: 10.1590/1518 8345.0963.2678] [This corrects the article doi: 10.1590/0104-1169.0498.2642] [This corrects the article doi: 10.1590/0104-1169.0478.2663]. PMID- 27409065 TI - Gap expansion in old-growth subarctic forests: the climate-pathogen connection. AB - We tested the hypothesis considering old-growth subarctic woodlands, free of fire, insect and stand-scale blowdown disturbances, to be at equilibrium with the climate. To do so, we explored the status of Hudsonian woodlands based on the natality/mortality ratio. The gap history of the woodland was reconstructed based on mapping and dating of dead gap-spruces (Picea mariana). Among the 25 gaps studied, 763 dead trees and only 14 saplings were recorded. The center of some gaps remained treeless over the last 1000 yr, and gap area doubled over the last 100 yr. The status of the tree population is in a demographic disequilibrium caused by the small replacement of dead spruces in all of the gaps. Episodes of 'mass' mortality occurred during several decades corresponding to years of favorable tree-ring growth. The natural process of gap-filling appears to be ineffective under current conditions. Good tree-ring growth of dying trees suggests abundant precipitation during the mortality episodes, but precipitation appears to be involved indirectly in the mortality process. The main cause of the widespread tree mortality during the last centuries of gap expansion appears to be biotic in origin. The impact of pathogenic fungal disease linked to late-lying snow cover is proposed for the mortality events. PMID- 27409066 TI - Synthetic Biological Protein Nanowires with High Conductivity. AB - Genetic modification to add tryptophan to PilA, the monomer for the electrically conductive pili of Geobacter sulfurreducens, yields conductive protein filaments 2000-fold more conductive than the wild-type pili while cutting the diameter in half to 1.5 nm. PMID- 27409067 TI - Genetic Analysis of Japanese Children With Acute Recurrent and Chronic Pancreatitis. AB - OBJECTIVES: Causes of acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) are sometimes difficult to determine in children. In such patients, genetic analysis may prove helpful. The present study analyzed mutations of cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), chymotrypsin C (CTRC), and carboxypeptidase A1 (CPA1) and investigated the clinical features of children with these mutations. METHODS: Genetic analyses of mutations in these 4 genes were conducted in 128 patients with ARP or CP. Characteristics of the patients showing mutations were investigated using medical records. RESULTS: Fifty of the 128 (39.1%) subjects had at least 1 mutation (median age at onset, 7.6 years). Abdominal pain was the presenting symptom of pancreatitis in 48 of the 50 patients (96%). Fifteen of those 50 patients (30.0%) had a family history of pancreatitis. Gene mutations were present in PRSS1 in 26 patients, SPINK1 in 23, CTRC in 3, and CPA1 in 5. In the 31 patients with mutations in SPINK1, CTRC, or CPA1, 16 (51.6%) had homozygous or heterozygous mutations with other mutations. Three patients underwent surgery and another 4 patients underwent endoscopy to manage ARP or CP. Although 3 of the 7 patients complained of mild abdominal pain, none of those 7 patients experienced any obvious episode of ARP after treatment. CONCLUSIONS: In pediatric patients with idiopathic ARP and CP, genetic analysis is useful for identifying the cause of pancreatitis. Early endoscopic or surgical treatment prevents ARP by extending the interval between episodes of pancreatitis in this population. PMID- 27409068 TI - A Dinitrogen Dicopper(I) Complex via a Mixed-Valence Dicopper Hydride. AB - Low-temperature reaction of the tris(pyrazolyl)borate copper(II) hydroxide [(iPr2) TpCu]2 (MU-OH)2 with triphenylsilane under a dinitrogen atmosphere gives the bridging dinitrogen complex [(iPr2) TpCu]2 (MU-1,2-N2 ) (3). X-ray crystallography reveals an only slightly activated N2 ligand (N-N: 1.111(6) A) that bridges between two monovalent (iPr2) TpCu fragments. While DFT studies of mono- and dinuclear copper dinitrogen complexes suggest weak pi-backbonding between the d(10) Cu(I) centers and the N2 ligand, they reveal a degree of cooperativity in the dinuclear Cu-N2 -Cu interaction. Addition of MeCN, CNAr(2,6 Me) , or O2 to 3 releases N2 with formation of (iPr2) TpCu(L) (L=NCMe, CNAr(2,6 Me2) ) or [(iPr2) TpCu]2 (MU-eta(2) :eta(2) -O2 ) (1). Addition of triphenylsilane to [(iPr2) TpCu]2 (MU-OH)2 in pentane allows isolation of a key intermediate [(iPr2) TpCu]2 (MU-H) (5). Although 5 thermally decays under N2 to give 3, it reduces unsaturated substrates, such as CO and HC=CPh to HC(O)H and H2 C=CHPh, respectively. PMID- 27409069 TI - Increased bone turnover, osteoporosis, progressive tibial bowing, fractures, and scoliosis in a patient with a final-exon SATB2 frameshift mutation. AB - Haploinsufficiency of SATB2 causes cleft palate, intellectual disability with deficient speech, facial and dental abnormalities, and other variable features known collectively as SATB2-associated syndrome. This phenotype was accompanied by osteoporosis, fractures, and tibial bowing in two previously reported adult patients; each possessed SATB2 mutations either predicted or demonstrated to escape nonsense-mediated decay, suggesting that the additional bone defects result from a dominant negative effect and/or age-dependent penetrance. These hypotheses remain to be confirmed, as do the specific downstream defects causing bone abnormalities. We report a SATB2 mutation (c.2018dupA; p.(H673fs)) in a 15 year-old patient whose SATB2-associated syndrome phenotype is accompanied by osteoporosis, fractures, progressive tibial bowing, and scoliosis. As this homeodomain-disrupting and predicted truncating mutation resides within the final exon of SATB2, escape from nonsense-mediated decay is likely. Thus, we provide further evidence of bone phenotypes beyond those typically associated with SATB2 associated syndrome in individuals with potential dominant-negative SATB2 alleles, as well as evidence for age-dependence of bone features. Elevations in alkaline phosphatase, urinary N-telopeptide/creatinine ratio, and osteocalcin in the patient indicate increased bone turnover. We propose surveillance and treatment with osteoclast inhibitors to prevent fractures and to slow progressive bone deformities. (c) 2016 Wiley Periodicals, Inc. PMID- 27409070 TI - Primary olfactory cortex in autism and epilepsy: increased glial cells in autism. AB - Autism Spectrum Disorder is characterized by sensory anomalies including impaired olfactory identification. Between 5 and 46 percent of individuals with autism have a clinical diagnosis of epilepsy. Primary olfactory cortex (piriform cortex) is central to olfactory identification and is an epileptogenic structure. Cytoarchitectural changes in olfactory cortex may underlie olfactory differences seen in autism. Primary olfactory cortex was sampled from 17 post-mortem autism cases with and without epilepsy, 11 epilepsy cases without autism and 11 typically developed cases. Stereological and neuropathological methods were used to quantify glial, pyramidal and non-pyramidal cell densities in layers of the piriform as well as identify pathological differences in this area and its neighbouring region, the olfactory tubercle. We found increased layer II glial cell densities in autism with and without epilepsy, which were negatively correlated with age and positively correlated with levels of corpora amylacea in layer I. These changes were also associated with greater symptom severity and did not extend to the olfactory tubercle. Glial cell organization may follow an altered trajectory of development with age in autism. The findings are consistent with other studies implicating increased glial cells in the autism brain. Altered cytoarchitecture may contribute to sensory deficits observed in affected individuals. This study provides evidence that autism is linked to alterations in the cytoarchitectural structure that underlies primary sensory processes and is not restricted to heteromodal ("higher") cognitive centers. PMID- 27409072 TI - Omitted Statistical Analysis Description and Errors in Figure. PMID- 27409071 TI - Differences in the prevalence of musculoskeletal symptoms among female and male custodians. AB - BACKGROUND: The prevalence of musculoskeletal symptoms among custodians is high. We sought to compare musculoskeletal symptoms between female and male custodians and to explore how task might affect this relationship. METHODS: A cross sectional study was performed among 712 custodians who completed a survey assessing upper extremity, back, and lower extremity musculoskeletal symptoms and exposure to cleaning tasks. Chi-square tests and logistic regression analyses were used to test for associations between gender, cleaning tasks, and musculoskeletal symptoms. RESULTS: Gender was significantly (P < 0.05) associated with musculoskeletal symptoms in chi(2) tests and multivariate analyses. The prevalence ratio of symptoms among women was roughly 50% higher than men, regardless of the tasks that workers performed. CONCLUSIONS: The prevalence of musculoskeletal symptoms differed for female and male custodians and appeared to be consistent across a range of job tasks. Am. J. Ind. Med. 59:841-852, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27409073 TI - Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome. PMID- 27409075 TI - Proceedings of the 3rd IPLeiria's International Health Congress : Leiria, Portugal. 6-7 May 2016. PMID- 27409074 TI - The long-term efficacy of combining nucleos(t)ide analog and low-dose hepatitis B immunoglobulin on post-transplant hepatitis B virus recurrence. AB - BACKGROUND: The aim of this study was to determine the long-term efficacy of nucleos(t)ide analog (NA) and low-dose hepatitis B immunoglobulin (HBIG) combination treatment for preventing post-transplant hepatitis B virus (HBV) recurrence. METHODS: A total of 296 patients with HBV-associated liver disease who underwent liver transplantation (LT) were enrolled. A combination of a daily NA and low-dose HBIG was used after LT. RESULTS: The median follow-up period was 46 months. HBV recurrence occurred in eight patients. The cumulative probability of HBV recurrence at 1, 3, 5, and 7 years was 1%, 3%, 3%, and 4%, respectively. Seven were on lamivudine (LMV) or adefovir dipivoxil (ADV), or LMV and ADV and HBIG combination treatment and one entecavir (ETV) and HBIG. With Cox regression analysis, HBV recurrence was determined to be associated with the presence of hepatocellular cancer (HCC) prior to LT (HR: 12.3, P=.02). Overall, 44 patients died. Survival was significantly better in the ETV or tenofovir disoproxil fumarate (TDF) and HBIG group than the other group (P<.001). CONCLUSION: The combination of ETV or TDF and low-dose HBIG achieved a more favorable prophylaxis against HBV recurrence after LT. The presence of HCC prior to LT was associated with post-transplant HBV recurrence. PMID- 27409076 TI - The Use and Reporting of the Cross-Over Study Design in Clinical Trials and Systematic Reviews: A Systematic Assessment. AB - BACKGROUND: Systematic reviews of treatment interventions in stable or chronic conditions often require the synthesis of clinical trials with a cross-over design. Previous work has indicated that methodology for analysing cross-over data is inadequate in trial reports and in systematic reviews assessing trials with this design. OBJECTIVE: We assessed systematic review methodology for synthesising cross-over trials among Cochrane Cystic Fibrosis and Genetic Disorders Group reviews published to July 2015, and assessed the quality of reporting among the cross-over trials included in these reviews. METHODOLOGY: We performed data extraction of methodology and reporting in reviews, trials identified and trials included within reviews. PRINCIPAL FINDINGS: We reviewed a total of 142 Cochrane systematic reviews including 53 reviews which synthesised evidence from 218 cross-over trials. Thirty-three (63%) Cochrane reviews described a clear and appropriate method for the inclusion of cross-over data, and of these 19 (56%) used the same method to analyse results. 145 cross-over trials were described narratively or treated as parallel trials in reviews but in 30 (21%) of these trials data existed in the trial reports to account for the cross-over design. At the trial level, the analysis and presentation of results were often inappropriate or unclear, with only 69 (32%) trials presenting results that could be included in meta-analysis. CONCLUSIONS: Despite development of accessible, technical guidance and training for Cochrane systematic reviewers, statistical analysis and reporting of cross-over data is inadequate at both the systematic review and the trial level. Plain language and practical guidance for the inclusion of cross-over data in meta-analysis would benefit systematic reviewers, who come from a wide range of health specialties. Minimum reporting standards for cross-over trials are needed. PMID- 27409078 TI - A Meta-Analysis and Systematic Review on the Association between Human Papillomavirus (Types 16 and 18) Infection and Esophageal Cancer Worldwide. AB - BACKGROUND: Esophageal cancer is a common and aggressive malignant tumor. This study aimed to investigate the association between human papillomavirus (HPV) Types 16 and 18 and esophageal carcinoma (EC) in the world population by conducting a meta-analysis. MATERIALS AND METHODS: Computerized bibliographic and manual searches were performed to identify all eligible literatures between 1982 and 2014. PUBMED (http://www.ncbi.nlm.nih.gov/pubmed/) and CNKI (http://www.cnki.net/) were the primary sources of case-control studies, and key words used include human papillomavirus, HPV, esophageal, esophagus, cancer, carcinoma, and tumor. All searches were performed by reviewing articles and abstracts cited in the published systematic reviews and case-control studies. Prospective studies that reported relative risk (RR) estimates with 95% CIs for the association between HPV and EC were included. RESULTS: Thirty-three randomized studies were identified, and the main features of these trials were included in this systematic review. HPV infection rate in the EC group was 46.5%, while HPV infection rate in the control group was 26.2% (OR = 1.62; 95% CI, 1.33 1.98). In China, the merger OR value was 1.62 (95% CI: 1.26-2.07); while in the Asian region, the merger OR value was 1.63 (95% CI: 1.29-2.04). There were statistical differences in HPV testing due to different detection methods such as PCR, IHC and ISH. In the PCR detection group, the merger OR value was 1.61 (95% CI: 1.33-1.95). CONCLUSIONS: These results indicate that HPV infection and the incidence of EC are closely associated. PMID- 27409077 TI - The Genomic Sequence of the Oral Pathobiont Strain NI1060 Reveals Unique Strategies for Bacterial Competition and Pathogenicity. AB - Strain NI1060 is an oral bacterium responsible for periodontitis in a murine ligature-induced disease model. To better understand its pathogenicity, we have determined the complete sequence of its 2,553,982 bp genome. Although closely related to Pasteurella pneumotropica, a pneumonia-associated rodent commensal based on its 16S rRNA, the NI1060 genomic content suggests that they are different species thriving on different energy sources via alternative metabolic pathways. Genomic and phylogenetic analyses showed that strain NI1060 is distinct from the genera currently described in the family Pasteurellaceae, and is likely to represent a novel species. In addition, we found putative virulence genes involved in lipooligosaccharide synthesis, adhesins and bacteriotoxic proteins. These genes are potentially important for host adaption and for the induction of dysbiosis through bacterial competition and pathogenicity. Importantly, strain NI1060 strongly stimulates Nod1, an innate immune receptor, but is defective in two peptidoglycan recycling genes due to a frameshift mutation. The in-depth analysis of its genome thus provides critical insights for the development of NI1060 as a prime model system for infectious disease. PMID- 27409079 TI - Cost and Impact of Voluntary Medical Male Circumcision in South Africa: Focusing the Program on Specific Age Groups and Provinces. AB - BACKGROUND: In 2012, South Africa set a goal of circumcising 4.3 million men ages 15-49 by 2016. By the end of March 2014, 1.9 million men had received voluntary medical male circumcision (VMMC). In an effort to accelerate progress, South Africa undertook a modeling exercise to determine whether circumcising specific client age groups or geographic locations would be particularly impactful or cost effective. Results will inform South Africa's efforts to develop a national strategy and operational plan for VMMC. METHODS AND FINDINGS: The study team populated the Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0) with HIV incidence projections from the Spectrum/AIDS Impact Module (AIM), as well as national and provincial population and HIV prevalence estimates. We derived baseline circumcision rates from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey. The model showed that circumcising men ages 20-34 offers the most immediate impact on HIV incidence and requires the fewest circumcisions per HIV infection averted. The greatest impact over a 15 year period is achieved by circumcising men ages 15-24. When the model assumes a unit cost increase with client age, men ages 15-29 emerge as the most cost effective group. When we assume a constant cost for all ages, the most cost effective age range is 15-34 years. Geographically, the program is cost saving in all provinces; differences in the VMMC program's cost-effectiveness across provinces were obscured by uncertainty in HIV incidence projections. CONCLUSION: The VMMC program's impact and cost-effectiveness vary by age-targeting strategy. A strategy focusing on men ages 15-34 will maximize program benefits. However, because clients older than 25 access VMMC services at low rates, South Africa could consider promoting demand among men ages 25-34, without denying services to those in other age groups. Uncertainty in the provincial estimates makes them insufficient to support geographic targeting. PMID- 27409080 TI - Visualization of the Epiblast and Visceral Endodermal Cells Using Fgf5-P2A-Venus BAC Transgenic Mice and Epiblast Stem Cells. AB - Fibroblast growth factor 5 (Fgf5) has been widely used as a marker for the epiblast in the postimplantation embryo and epiblast stem cells (mEpiSCs) in the mouse, making it valuable for study of differentiation of various tissues and epiblast cells in vivo and in vitro. Here, we report for the first time the generation of Fgf5-P2A-Venus BAC transgenic (Tg) mice and show that the BAC Tg can recapitulate endogenous Fgf5 expression in epiblast and visceral endodermal cells of E6.5 and 7.5 embryos. We also show that Fgf5-P2A-Venus BAC Tg mEpiSCs in the undifferentiated state expressed abundant Venus, and upon reprogramming into naive state, Venus was suppressed. Furthermore, while most Tg mEpiSCs expressed Venus abundantly, surprisingly the Tg mEpiSCs contained a minor subpopulation of Venus-negative cells that were capable of conversion to Venus-positive cells, indicating that even Fgf5 expression shows dynamic heterogeneity in mEpiSCs. Taken together, Fgf5-P2A-Venus BAC Tg mice and mEpiSCs generated in this study will be useful for developmental biology as well as stem cell biology research. PMID- 27409082 TI - A New Random Walk for Replica Detection in WSNs. AB - Wireless Sensor Networks (WSNs) are vulnerable to Node Replication attacks or Clone attacks. Among all the existing clone detection protocols in WSNs, RAWL shows the most promising results by employing Simple Random Walk (SRW). More recently, RAND outperforms RAWL by incorporating Network Division with SRW. Both RAND and RAWL have used SRW for random selection of witness nodes which is problematic because of frequently revisiting the previously passed nodes that leads to longer delays, high expenditures of energy with lower probability that witness nodes intersect. To circumvent this problem, we propose to employ a new kind of constrained random walk, namely Single Stage Memory Random Walk and present a distributed technique called SSRWND (Single Stage Memory Random Walk with Network Division). In SSRWND, single stage memory random walk is combined with network division aiming to decrease the communication and memory costs while keeping the detection probability higher. Through intensive simulations it is verified that SSRWND guarantees higher witness node security with moderate communication and memory overheads. SSRWND is expedient for security oriented application fields of WSNs like military and medical. PMID- 27409083 TI - Asia Pacific Stroke Conference 2016. Abstracts of the Annual Conference of theAsia Pacific Stroke Organization (APSO) Combined with Stroke Society of Australasia, Brisbane, Qld., Australia, July 14-17, 2016: Abstracts. PMID- 27409081 TI - The Actin Filament-Binding Protein Coronin Regulates Motility in Plasmodium Sporozoites. AB - Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics. PMID- 27409084 TI - Introducing Meta-Partition, a Useful Methodology to Explore Factors That Influence Ecological Effect Sizes. AB - The study of the heterogeneity of effect sizes is a key aspect of ecological meta analyses. Here we propose a meta-analytic methodology to study the influence of moderators in effect sizes by splitting heterogeneity: meta-partition. To introduce this methodology, we performed a meta-partition of published data about the traits that influence species sensitivity to habitat loss, that have been previously analyzed through meta-regression. Thus, here we aim to introduce meta partition and to make an initial comparison with meta-regression. Meta-partition algorithm consists of three steps. Step 1 is to study the heterogeneity of effect sizes under the assumption of fixed effect model. If heterogeneity is found, we perform step 2, that is, to partition the heterogeneity by the moderator that minimizes heterogeneity within a subset while maximizing heterogeneity between subsets. Then, if effect sizes of the subset are still heterogeneous, we repeat step 1 and 2 until we reach final subsets. Finally, step 3 is to integrate effect sizes of final subsets, with fixed effect model if there is homogeneity, and with random effects model if there is heterogeneity. Results show that meta-partition is valuable to assess the importance of moderators in explaining heterogeneity of effect sizes, as well as to assess the directions of these relations and to detect possible interactions between moderators. With meta-partition we have been able to evaluate the importance of moderators in a more objective way than with meta-regression, and to visualize the complex relations that may exist between them. As ecological issues are often influenced by several factors interacting in complex ways, ranking the importance of possible moderators and detecting possible interactions would make meta-partition a useful exploration tool for ecological meta-analyses. PMID- 27409085 TI - [Pancreas cancer]. PMID- 27409086 TI - [Rol of double-balloon enteroscopy in the management of small intestine diseases: experience in the National Hospital Guillermo Almenara Irigoyen, Lima, Peru]. AB - OBJECTIVE: Evaluate the diagnostic and therapeutic utility, safeness, efficacy and complications of double-balloon enteroscopy (DBE). MATERIAL AND METHODS: This prospective, descriptive study of DBE took place between July 2010 and June 2015 at the service of Gastroenterology of Hospital Nacional Guillermo Almenara Irigoyen- Lima Peru. 129 DBE were performed in 121 patients with the Fujinon EN 450T5 double balloon enteroscope, with conscious sedation and with previous bowel preparation. All of them signed an informed consent. RESULTS: The mean age was 56.6 years. Capsule endoscopy intestinal study was performed previously in 77 patients (63.6%). The most frequent indication for DBE was bleeding of middle intestine (61.2%). The approach used was more antegrade (69%). The maximum distance reached was 570 cm in antegrade method. The average duration for both routes is 117.45 minutes. Vascular ecstasies (56.1%) were the most frequent causes of obscure gastrointestinal bleeding. The diagnostic yield was 83.7%, higher than other series. The most widely used therapeutic procedure was argon plasma thermo coagulation. Like other studies, patients had good tolerance to the procedure and no major complications. CONCLUSIONS: In our patients studied the EDB has proven to be a secure, useful and efficient technique for the diagnosis and treatment of several diseases of the small intestine, especially in obscure gastrointestinal bleeding. PMID- 27409087 TI - [Microbiological and resistance profiles of community acquired and nosocomial intra abdominal infections in surgery of National Hospital Guillermo Almenara, Lima, Peru]. AB - OBJECTIVE: To determine the microbiological and resistance profiles of community acquired and nosocomial intra abdominal infections (IAIs) at the Surgery Service of Emergency and surgery critical care units from the Hospital Nacional Guillermo Almenara Irigoyen. MATERIAL AND METHODS: From August 1st, 2013 till July 31st, 2014, patients undergoing surgery/interventional drainage for IAIs were included. RESULTS: The suitable cultures for the analysis were 169 (74 bile and 95 no bile cultures; 142 community acquired and 27 nosocomials). The microorganims more frequently isolated were E. coli (63.3%), K. pneumoniae (12%) and Enterococcus spp. (10%). The 43.5% of E. coli and the 21.23% of Klebsiella were ESBL producers. The carbapenems were the most active agents in vitro (100%), while the quinolones showed high resistance (>50%). CONCLUSIONS: E. coli was the most common microorganism in the IAIs. Because of the quinolonea?TMs high a?oein vitroa?? resistance, they should not be recommended as initial empirical therapy. PMID- 27409088 TI - [Celiac disease and negative serology villous atrophy: histological comparison and immunohistochemical study of CD3, CD4, CD8 and CD56 lymphocytes]. AB - There is a group of enteropathies recently known as seronegative villous atrophy (SNVA), which can simulate celiac disease. OBJECTIVE: The aim of this study was to describe histological and immunohistochemical differences between a group of Celiac disease and SNVA patients. MATERIAL AND METHODS: Microscopy reexamination and Immunohistochemistry study were performed for a group of 15 celiac patients and 19 SNVA patients. Histological features as severe atrophy, crypt hyperplasia, plasma cells number, eosinophils number, neutrophils presence were studied; CD4, CD8, CD3, and CD56 markers were studied through immunohistochemistry. RESULTS: There was a significant difference between the frequency of observation of crypt hyperplasia (p=0.0348) and plasma cells (p=0.0348) in celiac disease patients than SNVA patients. In celiac disease was bigger. The number and distribution of CD 8, CD4 and CD56 lymphocytes was similar in both groups. The percentage of CD3 positive intraepithelial lymphocytes (p=0.0144) was higher in SNVA. CONCLUSION: Histological and immunohistochemical evaluation shows more similarities than differences. The differences found in this study suggest more humoral immune response in celiac disease than in SNVA. PMID- 27409089 TI - [Gastroduodenal mucosal injuries by aspirine. Management of the risks]. AB - BACKGROUND: Aspirin is one of the most used drugs around the Word, it has wide therapeutic indications. From its original indications, as analgesic and anti inflammatory and due to its platelet antiaggregate properties, this drug has become in the most employed medicine to prevent cardiovascular disease. Never the less, it is a drug with adverse effects and gastrointestinal toxicity indeed. OBJECTIVES: To identify the reasons of using aspirin, endoscopic findings on gastropathy caused by ASA and the relative risk of developing mucosal lesions. This based on a sample of adult patients in a chosen particular institution. MATERIALS AND METHODS: Prospective study of cases and controls, from January 1 to June 31, 2014, with patients with high digestive endoscopy. In the medical center Endocentro Bogota D.C. it was selected the people with aspirin consumption on 500 mg per day dose or less taken for more than six months prior the endoscopy. RESULTS: We selected 602 patients, 534 (88%) were women and 168 (12%) were men, with an age range from 17 to 92 years and with an average of 51.8 years. 107 patients were the aspirin users, 59 (55%) were women and 48 (45%) were men, with an range from 23 to 85 years and with an average of 58 years. The follow relative risks were found: gastroduodenal erosions RR=4.9 (95%IC 3.87-8.37), gastric ulcer RR=2.4 (95%IC 1.3-9.0), duodenal ulcer RR=2.8 (95%IC 1.3-7.0) any kind of gastrointestinal injury RR=5.5 (95%IC 4.1-7.2) aspirin users without any indication to the risk of develop any mucosa injury RR=2.0 (95%IC 1.4-3.0). CONCLUSIONS: This study showed an important proportion (18%) of dispatched aspirin users adults to digestive endoscopy, the 13.8% of them have a clear indication to use it, a substantial percent (13%) cannot inform any medical reason; the aspirin usage for more than six months in doses lower than 500 mg per day increases the mucosal gastroduodenal injury prevalence (58%)and relative risk of suffering these injuries are high. PMID- 27409090 TI - [Caustics injuries in the upper gastrointestinal tract: clinical and endoscopic features]. AB - OBJECTIVE: To describe the clinical and endoscopic features of caustics injuries in the upper gastrointestinal tract in patients of the National Hospital Daniel Alcides Carrion. MATERIALS AND METHODS: A descriptive study was conducted; the study populations were patients diagnosed with caustic ingestion who were admitted into the Gastroenterology service of the HNDAC to perform an upper endoscopy during the period of January 2009 to December 2012. We documented the type of caustic substance ingested, cause of intake, amount ingested, intake mode, signs or symptoms present, endoscopic findings as classified by Zargar, presence of complications and treatment performed. Analysis was performed comparing them based on the ingested caustic type: acid or alkali. RESULTS: We obtained 91 patients; the average age was 30.6A+/-16.3 years. Caustic substances ingested were: bleach (sodium hypochlorite) in 71 (78%) patients, muriatic acid (hydrochloric acid) in 18 (20%) patients, caustic soda in 2 (2%) patients. The average intake was 136ml (30-500 ml). The most frequent signs and symptoms were vomiting, abdominal pain, nausea and sore throat. The 46% of patients had injuries. 100% of patients who ingested acid and 33% who ingested alkali had lesions. Five (5%) patients had oropharyngeal lesions, 24 (26%) in the esophagus, 36 (40%) in the stomach and 12 (13%) in the duodenum. Grade I lesions were found in 10 (11%) patients, 16 (18%) patients with grade II lesions and 15 (16%) of patients with grade III, 12 patients who toke acid had lesions of grade III. Esophageal stricture was found in 2 (2%) patients, gastric stenosis in 7 (8%) patients and esophageal and gastric stenosis in 3 (3%) patients. Two patients required pneumatic dilation and 10 surgical treatments. CONCLUSION: Most injuries were found in the stomach. Acidic injuries occur more frequently and with greater severity than alkaline. Acidic substances produce esophageal or gastric stenosis more frequently than alkaline. PMID- 27409091 TI - [Comparison between Glascow-Blatchford, Rockall and AIMS65 scores in patients with upper gastrointestinal bleeding in a hospital in Lima, Peru]. AB - OBJECTIVE: Identify the best score that predicts each variable outcome (mortality, rebleeding and need for transfusion for more than 2 red blood cells pack) in patients with upper gastrointestinal bleeding until 30 days of the event. Material y methods: Patients included were those over 18 years, who had upper gastrointestinal bleeding between January 2014 to June 2015 in a general hospital of third level. The data was analyzed by the area under the curve ROC (Receiver Operating Characteristic). RESULTS: In total, there were 231 cases of upper gastrointestinal bleeding, 154 (66.7%) cases were male, the average age was 57.8 A+/- 20.02 years, the most common cause of bleeding was peptic ulcer: 111 (48.1%) cases, the mortality rate and rebleeding was 7.8% and 3.9% respectively. 5 patients were excluded from the analysis because they do not count with endoscopy study, the analysis was performed in 226 rest. In the evaluation of mortality, it was found an area under the curve ROC for Glasgow-Blatchford: 0.73, Rockall score: 0.86 and AIMS65 score: 0.90 (p<0.05) to predict rebleeding the Glasgow-Blatchford score: 0.73 Rockall score: 0.66 and AIMS65 score: 0.64 (p=0.41) and transfusion requirements of more than 2 globular packages the Glasgow-Blatchford score: 0.72, Rockall score: 0.67 and AIMS65 score: 0.77 (p=0.09). CONCLUSIONS: AIMS65 score is a good predictor of mortality and is useful in predicting the need for more than 2 transfusions of red blood cells pack compared to score Glasgow-Blatchford and Rockall score. PMID- 27409092 TI - Irritable bowel syndrome and intestinal parasites: a view from South America. AB - Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of uncertain etiology. Several studies have proposed the possible role of intestinal parasites in the pathogenesis of IBS. We aimed to summarize the epidemiological studies that describe a possible link between intestinal parasites and IBS, with special interest in endemic areas for intestinal parasitism such as South America. A comprehensive review of the literature was conducted by using the keywords: irritable bowel syndrome, intestinal parasites, protozoan infection, soil-transmitted helminths and South America. Giardia lamblia may cause IBS symptoms that can persist several years after effective treatment. Dientamoeba fragilis can cause IBS-like symptoms, but low sensitive parasitological techniques may fail to detect it. Entamoeba histolytica can cause a chronic non dysenteric colitis, but several studies have failed to find an association with IBS. The role of Blastocystis hominis in IBS remains controversial. In addition, epidemiological studies evaluating the effect of soil-transmitted helminths in IBS are scant. Symptoms elicited by intestinal parasites may resemble to those in IBS, especially in endemic areas such as South America, where both the prevalence of IBS and intestinal parasitism are high. Whether these organisms are the cause or contributing factors in IBS remains a subject of study. Routine parasitologicalexamination of stools in individuals who full-fit the criteria for IBS should be included upon initial assessment in endemic countries. PMID- 27409093 TI - [Actinic enteritis as a cause of digestive bleeding of obscure origin]. AB - Chronic actinic enteritis is a malfunction of the small bowel, occurring in the 6 months post-radiotherapy, and it can be manifestated as malabsortion, stenosis, fistula formation, local abscesses, perforation and bleeding, We report a case of an elderly patient who presents an episode of obscure gastrointestinal bleeding (OGIB) secondary to actinic enteritis. She is a 64-year- old female patient with the past medical history of cervical cancer who received radiotherapy and brachytherapy. One year after the treatment, the patient presents a chronic episode of melena and symptomatic anemia and 1 week before the admission she had hematochezia. At admission she has hemodynamic instability with a hemoglobin value of 2.7 gr/dl. We did an upper endoscopy, a colonoscopy and abdomino-pelvic tomography without any findings of the bleedinga?TMs source. Reason why an endoscopic capsule was done, showing bleeding areas in the medial and distal small bowel. The patient had another gastrointestinal bleeding requiring a surgery where they decide to do a resection of the small bowel and a right hemicholectomy. The pathology was compatible with actinic enteritis. The patient after the surgery had a torpid evolution, and finally dies. We describe this case and do a review of all the existent data around the world, because is the first case reported in Peru of an actinic enteritis as a cause of OGIB. PMID- 27409094 TI - [Peutz Jeghers syndrome. Report of five cases]. AB - The Peutz Jeghers Syndrome (PJS) is characterized by gastrointestinal hamartomatous polyps and mucocutaneous pigmentation, are at high risk of bowel resections because ischemia secondary to intussusception. The risk of gastrointestinal cancer is nine more than the general population. We report five patients diagnosed with SPG, four had intestinal intussusception, one upper gastrointestinal bleeding and one died with pancreatic neoplasia. PMID- 27409095 TI - [Mucinous adenocarcinoma of the appendix. Report of a case]. AB - Mucinous adenocarcinoma of the appendix is a rare neoplasm with an incidence rate of 0.08% of all malignancies. The diagnosis is usually made by biopsy because its clinical presentation may mimic other diseases of structures located in the right lower quadrant. Currently, the treatment is still controversial, being surgery the best option. This report describes a patient with a history of appendectomy 27 years ago that is hospitalized for a painful mass in the lower abdomen associated with carcinoembryonic antigen of 138 ng/dl. PMID- 27409096 TI - [Duodenal adenocarcinoma: a rare diagnosis]. AB - Duodenal adenocarcinoma is a rare disease whose symptoms are usually vomit, weight loss and lack of appetite; appearing more frequently in men in their sixties. Upper gastrointestinal endoscopy is the technique chosen for its diagnosis, also relying on other techniques such as endoscopic ultrasonography or computed tomography for the extension study. In this regard we report the case of a patient diagnosed of bulbar duodenal adenocarcinoma in our hospital. PMID- 27409097 TI - [Association between ulcerative colitis and primary esclerosing cholangitis]. AB - Ulcerative Colitis (UC) is associated to Primary Sclerosing Cholangitis (PSC) in 80% of cases, and this association is more common than the one with Crohna?TMs disease. Nevertheless, the prevalence of PSC in patients with UC is only 2.9% in Latin America. We present the case of a female patient who presents a clinical history characterized for chronic diarrhea of one year of evolution, associated to fever, oral ulcers and loss of weight. In the laboratory results there is an elevation in the following: alkaline phosphatase, GGT, ALT and AST, for that reason we decide to do an abdominal ultrasound finding a hepatomegaly. In the colonoscopy we found an ulcerative colitis. Later, we do a magnetic resonance cholangiopancreatography, because of the diagnosis of UC and the abnormalities at the liver function tests, diagnosing PSC associated to UC. At that moment, the patient starts treatment with sulfasalazine that is stopped because of an adverse effect, starting prednisone and azathioprine. The patient then is discharged with the medication already mentioned and has a favorable clinical outcome. We decide to report the case because is the second reported case in Peru, being this association not commonly found in the South hemispheric. PMID- 27409098 TI - Colorectal cancer in Latin America. Novel concerns. PMID- 27409099 TI - Mechanical analysis and force chain determination in granular materials using digital image correlation. AB - The mechanical behaviors of granular materials are governed by the grain properties and microstructure of the materials. We conducted experiments to study the force transmission in granular materials using plane strain tests. The large amount of nearly continuous displacement data provided by the advanced noncontact experimental technique of digital image correlation (DIC) has provided a means to quantify local displacements and strains at the particle level. The average strain of each particle could be calculated based on the DIC method, and the average stress could be obtained using Hooke's law. The relationship between the stress and particle force could be obtained based on basic Newtonian mechanics and the balance of linear momentum at the particle level. This methodology is introduced and validated. In the testing procedure, the system is tested in real 2D particle cases, and the contact forces and force chain are obtained and analyzed. The system has great potential for analyzing a real granular system and measuring the contact forces and force chain. PMID- 27409100 TI - Integrated label-free optical biochemical sensor with a large measurement range based on an angular grating-microring resonator. AB - We propose and design a photonic-integrated optical biochemical sensor, which comprises a microring resonator and angular gratings in a silicon-on-insulator waveguide. With the combination of the angular gratings, the measurement range of the angular grating-microring resonator-based sensor significantly increases without the restriction of a free spectral range. Optimization of the several key structural parameters is investigated to achieve favorable transmission properties. A high-quality factor of more than 1.03*105 can meet the requirements of high sensitivity and low detection limit. The simulation results on the biochemical bulk sensing show that a concentration sensitivity of more than 95.27 pm/% and detection limit of less than 0.329% can be obtained. A large measurement range of 50.2 nm is achieved by the combination of the angular gratings. The investigation on the combination of microring resonator and angular grating is a valuable exploration of the liquid and gas biomedical sensing for the ultra-large measurement range. PMID- 27409101 TI - Wide-area and omnidirectional optical detector arrays using modular optical elements. AB - This paper presents novel, modular optical detector arrays of various shapes and configurations. Recently developed Modular Optical Wireless Elements (MOWE) architecture serves as the basis for large and complex optical detector arrays that can be constructed as geometric shells and provide wide-area even omnidirectional field-of-view (FoV). Programmable optical modules synchronously sample the environment, and then route measurements to the user through a dedicated electrical backbone. The arrays are inexpensive, easy to construct, and can be made with homogeneous/inhomogeneous optical properties. Applications include remote sensing, motion detection, optical navigation, and medical imaging, among others. We present the MOWE detector array concept with a detailed optical analysis and a suggested design methodology, as well as a number of various demonstrations. We also utilize wavelength-diversity of MOWE arrays to demodulate two overlapping signals, showing that many diversity-based algorithms can be conveniently prototyped and implemented. PMID- 27409102 TI - Compact high-resolution Littrow conical diffraction spectrometer. AB - This paper presents a compact high-resolution Littrow conical diffraction spectrometer (LCDS) that includes an echelle grating for horizontally dispersing the incident light beam into several high diffraction orders, a prism for vertically separating the overlapping diffraction orders, and a shared focusing lens used for both the incident and dispersed beams. The unique design of the optics enables the LCDS to give high dispersion on the detector without requiring a large field of view and, therefore, to achieve the benefits of high spectral resolution and compactness. The use of the Littrow conical diffraction coupled with the shared focusing lens makes the LCDS more compact. The formulas of the footprint of the dispersed spectra are derived, and the numerical simulation is given. The design calculations for application of the LCDS to an optical coherence tomography system are illustrated by an example. PMID- 27409103 TI - Extended-field coverage hyperspectral camera based on a single-pixel technique. AB - A spectral single-pixel imaging system facilitates effective image compression, but the imaging region is limited by its single detector. This paper presents a hyperspectral camera that allows extended-field coverage to be collected by one detector. Compressive data of a large field of view is achieved by our highly sensitive detection camera, which can be extended to near-infrared or infrared spectral monitoring. We acquire a hyperspectral datacube of 256*256 spatial pixels and 3 nm spectral resolution at a sampling rate of 25%. Finally, we apply our camera to monitoring fruit freshness nondestructively by differentiating a banana's ripeness over time. PMID- 27409104 TI - Experimental realization of an achromatic magnetic mirror based on metamaterials. AB - Our work relates to the use of metamaterials engineered to realize a metasurface approaching the exotic properties of an ideal object not observed in nature, a "magnetic mirror." Previous realizations were based on resonant structures that implied narrow bandwidths and large losses. The working principle of our device is ideally frequency-independent, it does not involve resonances and it does not rely on a specific technology. The performance of our prototype, working at millimeter wavelengths, has never been achieved before and it is superior to any other device reported in the literature, both in the microwave and optical regions. The device inherently has large bandwidth (144%), low losses (<1%), and is almost independent of incidence angle and polarization state, and thus approaches the behavior of an ideal magnetic mirror. Applications of magnetic mirrors range from low-profile antennas, absorbers to optoelectronic devices. Our device can be realized using different technologies to operate in other spectral regions. PMID- 27409105 TI - Coherent imaging with a resonance domain diffractive lens in laser light. AB - We investigated coherent imaging with a binary off-axis resonance domain diffractive lens using three lasers in visible wavelengths. The relations between the dispersion of this lens, shape of its point spread function, and spectral properties of these lasers were analyzed theoretically and experimentally. In particular, we measured the point spread function, imaging contrast, and diffraction efficiency. Experimental results proved the feasibility of imaging with low distortion and more than 83% diffraction efficiency in laser light. PMID- 27409106 TI - Design of a polymer-filled silicon nitride strip/slot asymmetric hybrid waveguide for realizing both flat dispersion and athermal operation. AB - An asymmetric strip/slot hybrid silicon nitride waveguide is designed to simultaneously realize athermal operation and flat dispersion. The slot filling and upper cladding materials are negative thermal-optical coefficient (TOC), low refractive index polyurethane acrylate, while the left and right cladding layers are positive TOC, high refractive index silicon nitride. With suitable waveguide parameter selection, an optimum strip/slot hybrid silicon nitride waveguide exhibits an effective TOC of 1.263*10-7/K at 1550 nm, flattened dispersion in the wavelength range from 1200 to 1800 nm with the maximum dispersion of 30.51 ps/(nm.km), and a minimum of 10.89 ps/(nm.km). The proposed hybrid waveguide has great potential in building up broadband athermal microresonator optical frequency combs. PMID- 27409107 TI - Features of the non-linearity specific to two-phonon light scattering controlled by elastic waves with linear losses: potentials for high-resolution spectral analysis. AB - New physical details inherent in the non-collinear two-phonon Bragg light scattering controlled by ultrahigh frequency elastic waves of finite amplitude are studied in wide-aperture crystals exhibiting moderate linear acoustic losses. Recently, it had been demonstrated that the Bragg regime of light scattering exhibits the specific acousto-optical non-linearity with a set of unit-level maxima. Now, additionally to our previous analysis, we present an advanced analytical description of this phenomenon in the amplitude and frequency domains, and what is more, we orient it mainly at the second unit-level maximum. This non linearity, together with the linear acoustic losses in an acousto-optical cell, produces a new effect of non-linear apodization. The light beam leaving the cell can suppress the side lobes and grow the dynamic range within the potential optical spectrum analysis. After that, we characterize comprehensively an acousto optical cell, made of calomel and working within the second maximum of two-phonon light scattering, as a dispersive optical component. Finally, the results of our proof-of-principle experiments with the calomel-made cell operating in the chosen regime are presented and discussed. PMID- 27409108 TI - Unmixing multiple adjacent fluorescent targets with multispectral excited fluorescence molecular tomography. AB - Fluorescence molecular tomography (FMT) can visualize biological activities at cellular and molecular levels in vivo, and has been extensively used in drug delivery and tumor detection research of small animals. The ill-posedness of the FMT inverse problem makes it difficult to reconstruct and unmix multiple adjacent fluorescent targets that have different functional features but are labeled with the same fluorochrome. A method based on independent component analysis for multispectral excited FMT was proposed in our previous study. It showed that double fluorescent targets with certain edge-to-edge distance (EED) could be unmixed by the method. In this study, the situation is promoted to unmix multiple adjacent fluorescent targets (i.e., more than two fluorescent targets and EED=0). Phantom experiments on the resolving ability of the proposed algorithm demonstrate that the algorithm performs well in unmixing multiple adjacent fluorescent targets in both lateral and axial directions. And also, we recovered the locational information of each independent fluorescent target and described the variable trends of the corresponding fluorescent targets under the excitation spectrum. This method is capable of unmixing multiple fluorescent targets with small EED but labeled with the same fluorochrome, and may be used in imaging of nonspecific probe targeting and metabolism of drugs. PMID- 27409109 TI - In situ plankton and fish detection based on optical gated sampling. AB - For the in situ detection technologies of planktons and fishes, optical cameras traditionally have a small and fixed sampling volume with a strong target-sized dependent (typically<1 mm), and imaging sonar has lower spatial resolution (typically>2 cm) with a problem of species identification. To solve the above problems, this paper proposes an in situ detection method of optical gated sampling for millimeter- to centimeter-scale plankton and fish detection. In this method, the sampling volume can be flexibly adjusted by matching the temporal parameters of gate pulses and illuminator laser pulses to satisfy target observation with different sizes. The gated sampling suppresses the backscattering of water and also filters the environment background so that transparent planktons can be detected by high contrast. Furthermore, the sampling volume is determined by the convolution of gate pulses and laser pulses, and thus the target abundance is derived. Theory and simulation of abundance measurement are established. In experiments, transparent jellyfishes are recorded with a spatial resolution of better than 100 MUm. In addition, proof experiments of sampling volume adjustment and abundance measurement are demonstrated. PMID- 27409110 TI - Methodology of contact stress analysis of gearwheel by means of experimental photoelasticity. AB - The subject of this paper is the analysis of contact stresses that occur between the teeth of a gear. The analysis was carried out by means of reflection photoelasticity, which is an experimental method rarely used in this field. Contact stresses assessed in the experiment are compared with values assessed through an analytical calculation while using the Airy stress function or Hertzian relations. PMID- 27409111 TI - Polarimetric parameters associated to special microstructured fibers. AB - The Mueller matrices associated to six homemade special index-guiding microstructured fibers are determined at a transmission wavelength of 1550 nm. Diattenuation, polarizance, and polarization-dependent loss, among other polarimetric parameters, are determined from the Mueller matrix associated to a 2 m length of each fiber studied here. Results show that the fiber fabrication parameters have a clear effect on the output degree of polarization (DoP), providing an inverse relationship between the DoP output and the relative hole diameter, the d/Lambda value. PMID- 27409112 TI - Size and dielectric-environment dependence of transversal resonance modes of localized surface plasmons in silver nanorods. AB - Tuning transversal resonance modes of localized surface plasmons (LSPs) by the size and the ambient dielectric medium of Ag nanorods is presented. It is found that the resonance wavelength and intensity of the transversal modes of LSPs are closely related to the dimensions of the Ag nanorods embedded in anodic aluminum oxide membranes. The transversal resonance peak exhibits obvious redshifts from 365 to 396 nm with increasing nanorod diameter from 40 to 80 nm, and the resonance intensity remarkably enhances with increasing nanorod diameter. In addition, it is observed that the transversal resonance modes of LSPs in Ag nanorods are strongly sensitive to their surrounding dielectric medium such as water, ethanol, and cetyltrimethylammonium bromide, and the transversal resonance peak distinctly redshifts from 422 to 467 nm when the refractive index of the dielectric medium increases from 1.342 to 1.435. As a result, a refractive index sensitivity of up to 484 nm/RIU can be achieved based on the transversal resonance modes. The transverse resonance modes of LSPs in the Ag nanorods can be used for sensitive quantification of chemical and biological species. PMID- 27409113 TI - Passive Q-switching of microchip lasers based on Ho:YAG ceramics. AB - A Ho:YAG ceramic microchip laser pumped by a Tm fiber laser at 1910 nm is passively Q-switched by single- and multi-layer graphene, single-walled carbon nanotubes (SWCNTs), and Cr2+:ZnSe saturable absorbers (SAs). Employing SWCNTs, this laser generated an average power of 810 mW at 2090 nm with a slope efficiency of 68% and continuous wave to Q-switching conversion efficiency of 70%. The shortest pulse duration was 85 ns at a repetition rate of 165 kHz, and the pulse energy reached 4.9 MUJ. The laser performance and pulse stability were superior compared to graphene SAs even for a different number of graphene layers (n=1 to 4). A model for the description of the Ho:YAG laser Q-switched by carbon nanostructures is presented. This modeling allowed us to estimate the saturation intensity for multi-layered graphene and SWCNT SAs to be 1.2+/-0.2 and 7+/-1 MW/cm2, respectively. When using Cr2+:ZnSe, the Ho:YAG microchip laser generated 11 ns/25 MUJ pulses at a repetition rate of 14.8 kHz. PMID- 27409114 TI - Research on temperature field of KDP crystal under ion beam cleaning. AB - KH2PO4 (KDP) crystal is a kind of excellent nonlinear optical component used as a laser frequency conversion unit in a high-power laser system. However, KDP crystal has raised a huge challenge in regards to its fabrication for high precision: KDP crystal has special physical and chemical characteristics. Abrasive-free water-dissolution magnetorheological finishing is used in KDP figuring in our lab. But the iron powders of MRF fluid are easily embedded into the soft surface of KDP crystal, which will greatly decrease the laser-induced damage resistance. This paper proposes to utilize ion beam figuring (IBF) technology to figure and clean the surface of a KDP component. Although IBF has many good performances, the thermal effect control is a headachy problem for the KDP process. To solve this problem, we have established its thermal effect models, which are used to calculate a component's surface temperature and thermal gradient in the whole process. By this way, we can understand how to control a temperature map and its gradient in the IBF process. Many experiments have been done to validate and optimize this method. Finally, a KDP component with the size of 200*200*12 mm is successfully processed by this method. PMID- 27409115 TI - Controlling the propagation of an optical vortex through two-dimensional ordered and disordered waveguide arrays using topological charge. AB - In this paper, we study the propagation of a radially symmetric optical vortex whose amplitude is independent of topological charge in ordered and disordered 2D arrays of coupled waveguides. It is first demonstrated that the topological charge variation affects the beam spreading in the completely ordered arrays. For a low refractive index contrast between waveguides and their surroundings, the effective width at the output end of the optical lattice versus topological charge shows an oscillatory behavior. However, for a higher refractive index contrast, as the topological charge increases from 0 to 10, the effective width reaches a maximum value and then falls. Then, we investigate the effects of topological charge variation on the wave propagation through the waveguide array in the presence of different disorder strengths. Our results here confirm that the behavior of effective width versus the topological charge in the disordered array significantly depends on the average of the refractive index of the waveguides. Although the intensity of the input radially symmetric vortex beam is independent of the topological charge, for low disorder levels, the effective width and intensity distribution at the output end is strongly sensitive to the topological charge or the polar phase of the vortex beam. It is also demonstrated that, for strongly disordered arrays, the effective width and output beam profile shows no considerable change with variation of the topological charge. These effects are due to the discrete diffraction phenomenon and its dependence on the helical wavefront of the optical vortex whose form is determined by the topological charge. Therefore, it is demonstrated here that angular phase affects the beam broadening in an array of coupled optical waveguides. PMID- 27409116 TI - Interferometric out-of-focus imaging of ice particles with overlapping images. AB - It is shown that the size and relative positions of two irregular rough particles can be analyzed using interferometric out-of-focus imaging despite the overlapping of their out-of-focus images. Simulations are confirmed by experiments done with ice particles generated in a freezing column. PMID- 27409117 TI - Laser multi-reflection differential confocal long focal-length measurement. AB - We propose a new laser multi-reflection differential confocal focal-length measurement (LDCFM) method to meet the requirements of high-precision measurements of long focal lengths. An optical flat and a reflector are placed behind a test lens for reflecting the measuring beam repeatedly. Then, LDCFM uses the property that the null points of differential confocal response curves precisely correspond to the convergence points of the multi-reflected measuring beam to exactly determine the positions of the convergence points accurately. Subsequently, the position variation of the reflector is measured with different reflection times by using a distance-measuring instrument, and thereby the long focal length is measured precisely. Theoretical analyses and preliminary experimental results indicate that the LDCFM method has a relative expanded standard uncertainty (k=2) of 0.04% for the test lens with a focal length of 9.76 m. The LDCFM method can provide a novel approach for high-precision focal-length measurements. PMID- 27409118 TI - Design of anamorphic magnification high-numerical aperture objective for extreme ultraviolet lithography by curvatures combination method. AB - An anamorphic magnification extreme ultraviolet (EUV) lithographic objective could increase the size of the exposure field at a wafer in the orthogonal scanning direction to improve the throughput of the lithographic system. In this paper, we present a curvatures combination method for an anamorphic magnification EUV lithographic objective with high numerical aperture (NA). This method achieves an anamorphic magnification initial structure by use of the double curvature surfaces, which are formed by combining the curvatures of the corresponding surfaces into two coaxial spherical systems. A series of control measures is taken to design the two coaxial spherical systems for ensuring the rationalities of the initial structure and the surfaces after combining. The image quality of the anamorphic initial structure is optimized by a gradual optimization process. Finally, as an example, we design an Mx1/4 and My1/8 anamorphic magnification EUV lithographic objective with the presented design method. This objective achieves 0.5 NA and a 26 mm*16.5 mm exposure field at the wafer. The wavefront error RMS reaches 0.06lambda (lambda=13.5 nm), and the distortion is less than 2.8 nm. The design result proves the availability of the curvatures combination method. PMID- 27409119 TI - Geometrical constraint experimental determination of Raman lidar overlap profile. AB - A simple experimental method to determine the overlap profile of Raman lidar is presented in this paper. Based on Mie and Raman backscattering signals and a geometrically constrained condition, the overlap profile of a Raman lidar system can be determined. Our approach simultaneously retrieves the lidar ratio of aerosols, which is one of the most important sources of uncertainty in the overlap profile determination. The results indicate that the overlap factor is significantly influenced by the lidar ratio in experimental methods. A representative case study indicates that the correction of the overlap profile obtained by this method is practical and feasible. PMID- 27409120 TI - Dual-wavelength passively Q-switched Nd:GYSGG laser by tungsten disulfide saturable absorber. AB - A dual-wavelength passively Q-switched Nd:GYSGG laser using vacuum evaporating tungsten disulfide (WS2) as a saturable absorber was demonstrated for the first time to the best of our knowledge. The WS2 saturable absorber was prepared simply by evaporating nanometer WS2 powders onto a quartz substrate in a vacuum. By inserting the WS2 saturable absorber into the laser cavity, stable Q-switched laser operation was achieved with a maximum average output power of 367 mW, a pulse repetition rate of 70.7 kHz, the shortest pulse width of 591 ns, and pulse energy of about 1.05 MUJ. By vacuum evaporation method, a high-quality WS2 saturable absorber can be produced, and it seems to be a suitable method for fabrication of 2D transition metal dichalcogenides. PMID- 27409121 TI - Luminous efficacy enhancement of ultraviolet-excited white light-emitting diodes through multilayered phosphor-in-glass. AB - To enhance the luminous efficacy of ultraviolet-excited white light-emitting diodes (WLEDs), a novel packaging structure that is based on a multilayered red, green, and blue (RGB) phosphor-in-glass (PiG) was proposed. The RGB PiG was prepared by screenprinting and low temperature sintering, and the effects of different configuration orders of RGB phosphor layers on the optical performance of WLEDs were studied. Compared with the conventional mixed-RGB PiG, the luminous efficacy of WLEDs packaged by the multilayered PiG with the order of R-G-B is increased by 8.2% at the driving current of 500 mA, and the corresponding correlated color temperature (CCT) and color rendering index (CRI) are 2984 K and 86.8, respectively. Moreover, the WLEDs packaged by multilayered G-R-B PiG yield the highest luminous efficacy of 27.19 lm/W at the expense of color quality, which is still an acceptable warm light, with a CCT of 3326 K and a CRI of 84.2. PMID- 27409122 TI - Diffractive optics development using a modified stack-and-draw technique. AB - We present a novel method for the development of diffractive optical elements (DOEs). Unlike standard surface relief DOEs, the phase shift is introduced through a refractive index variation achieved by using different types of glass. For the fabrication of DOEs we use a modified stack-and-draw technique, originally developed for the fabrication of photonic crystal fibers, resulting in a completely flat element that is easy to integrate with other optical components. A proof-of-concept demonstration of the method is presented-a two dimensional binary optical phase grating in the form of a square chessboard with a pixel size of 5 MUm. Two types of glass are used: low refractive index silicate glass NC21 and high refractive index lead-silicate glass F2. The measured diffraction characteristics of the fabricated component are presented and it is shown numerically and experimentally that such a DOE can be used as a fiber interconnector that couples light from a small-core fiber into the several cores of a multicore fiber. PMID- 27409123 TI - Gain change by adjusting the pumping wavelength in an end-pumped Nd:YVO4 amplifier. AB - In this paper, the performance of an end-pumped laser amplifier was experimentally studied by adjusting the pumping wavelength of a laser diode. An interesting phenomenon was observed: that the gain would decrease with an increase in absorbed pump power. The scaled output power of 0.3 at. % doped 20 mm long Nd:YVO4 crystal decreased from 0.48 to 0.2 W when the absorbed pump power increased from 17.5 to 17.8 W. Theoretical analysis was demonstrated according to our previous model. The long crystal length is the main reason for the observed phenomenon. This phenomenon could be utilized to enhance amplifier gain and improve thermal performance, including the maximal temperature and thermal stress of the crystal. PMID- 27409124 TI - Varied-line-spacing switchable holographic grating using polymer-dispersed liquid crystal. AB - A varied-line-spacing switchable holographic grating is demonstrated through a changeable interference pattern recorded in polymer-dispersed liquid crystal. The pattern is generated by the interference between one plane wave and another cylindrical wave. The line spacing and the period of grating can be controlled by varying the distance between the cylindrical lens and the grating sample and by changing the exposure angle between the two beams. Experimental period measurements and calculations show good agreement with the theoretical results. High diffraction efficiency of more than 80% for the middle period of the grating has been achieved under appropriate exposure time of 120 s and intensity of 19.1 mW/cm2. In addition, the diffraction can be switched on and off by virtue of the external driving voltage of approximately 120 V. The grating also possesses a fast response with a rise time of 300 MUs and a fall time of 750 MUs. This grating, which can change the period in the grating structure to allow switchable diffraction of transmitted light, shows great potential application for diffractive optics. PMID- 27409125 TI - Temperature measurements in metalized propellant combustion using hybrid fs/ps coherent anti-Stokes Raman scattering. AB - We apply ultrafast pure-rotational coherent anti-Stokes Raman scattering (CARS) for temperature and relative oxygen concentration measurements in the plume emanating from a burning, aluminized ammonium-perchlorate propellant strand. Combustion of these metal-based propellants is a particularly hostile environment for laser-based diagnostics, with intense background luminosity and scattering from hot metal particles as large as several hundred micrometers in diameter. CARS spectra that were previously obtained using nanosecond pulsed lasers in an aluminum-particle-seeded flame are examined and are determined to be severely impacted by nonresonant background, presumably as a result of the plasma formed by particulate-enhanced laser-induced breakdown. Introduction of femtosecond/picosecond (fs/ps) laser pulses improves CARS detection by providing time-gated elimination of strong nonresonant background interference. Single laser-shot fs/ps CARS spectra were acquired from the burning propellant plume, with picosecond probe-pulse delays of 0 and 16 ps from the femtosecond pump and Stokes pulses. At zero delay, nonresonant background overwhelms the Raman resonant spectroscopic features. Time-delayed probing results in the acquisition of background-free spectra that were successfully fit for temperature and relative oxygen content. Temperature probability densities and temperature/oxygen correlations were constructed from ensembles of several thousand single-laser shot measurements with the CARS measurement volume positioned within 3 mm or less of the burning propellant surface. The results show that ultrafast CARS is a potentially enabling technology for probing harsh, particle-laden flame environments. PMID- 27409126 TI - Shaping of steel mold surface of lens array by electrical discharge machining with spherical ball electrode. AB - We propose a method for fabricating a spherical lens array mold by electrical discharge machining (EDM) with a ball-type electrode. The electrode is constructed by arranging conductive spherical balls in an array. To fundamentally examine the applicability of the proposed EDM method to the fabrication of lens array molds, we use an electrode having a single ball to shape a lens array mold made of stainless steel with 16 spherical elements, each having a maximum depth of 0.5 mm. As a result, a mold surface is successfully shaped with a peak-to valley shape accuracy of approximately 10 MUm, and an average surface roughness of 0.85 MUm. PMID- 27409128 TI - Primordial Prevention and Wearable Health Devices: The Wearables in Cardiology. PMID- 27409127 TI - [Scientific Assessment of 350 Failed Metasul-LDH(r) Hip Prostheses with DUROM(r) Acetabulum Component with Probable Conus Insufficiency, Implanted in a Single Centre During 2003 to 2008]. AB - Introduction: The revision rates were high for patients with Metasul-LDH(r) hip prosthesis (LDH = large-diameter head) with DUROM(r) acetabulum components implanted in a single centre between 2003 and 2008. This suggested that there was a system-related weakness in total hip replacements with large diameter heads. It was suspected that the tapered connection between head and stem was responsible for the implantation failure. This led to a scientific reappraisal of the unsuccessful hip prostheses, in order to clarify whether there was a tribological problem or a cone failure. Method: To this end, data on serum metal concentrations, types of prosthesis and stem alloys were collected and analysed for the 315 patients with 350 DUROM(r)-LDH-HTP. Results: There were significant differences between blood metal concentrations in patients with different types of stem. For patients with titanium stems, there were more serious affects on bone substance surrounding the affected joint, and significantly higher serum cobalt concentrations. Conclusion: It was concluded that the problem did not lie with the tribology of the sliding surfaces, but with the cone-stem connection. PMID- 27409129 TI - Case 4/2016: 32-Year-Old Female, with Critical Pulmonary Valve Stenosis. Operated at 4 Months of Age, in Normal Healing Evolution. PMID- 27409130 TI - Drug-Coated Balloon Treatment of Very Late Stent Thrombosis Due to Complicated Neoatherosclerosis. AB - We describe the treatment of a patient presenting with very-late stent thrombosis with the use of a drug-coated balloon. In this patient, optical coherence tomography disclosed that ruptured and complicated neoatherosclerosis was the underlying substrate responsible for the episode of very-late stent thrombosis. The potential use of drug-coated balloons in this unique scenario is discussed. PMID- 27409131 TI - Left Ventricular Rigid Body Rotation in Ebstein's Anomaly from the MAGYAR-Path Study. PMID- 27409132 TI - Predictors of Atrial Fibrillation Recurrence in Hyperthyroid and Euthyroid Patients. PMID- 27409133 TI - Can reactivity to stress and family environment explain memory and executive function performance in early and middle childhood? AB - INTRODUCTION: According to the literature, children's overall reactivity to stress is associated with their socioeconomic status and family environment. In turn, it has been shown that reactivity to stress is associated with cognitive performance. However, few studies have systematically tested these three constructs together. OBJECTIVE: To investigate the relationship between family environment, salivary cortisol measurements and children's memory and executive function performance. METHOD: Salivary cortisol levels of 70 children aged 9 or 10 years were measured before and after performing tasks designed to assess memory and executive functions. Questionnaires on socioeconomic issues, family environment and maternal psychopathologies were administered to participants' families during the children's early childhood and again when they reached school age. RESULTS: Data were analyzed by calculating correlations between variables and conducting hierarchical regression. High cortisol levels were associated with poorer working memory and worse performance in tasks involving executive functions, and were also associated with high scores for maternal psychopathology (during early childhood and school age) and family dysfunction. Family environment variables and changes in cortisol levels explain around 20% of the variance in performance of cognitive tasks. CONCLUSION: Family functioning and maternal psychopathology in early and middle childhood and children's stress levels were associated with children's working memory and executive functioning. PMID- 27409134 TI - Cross-cultural adaptation of the Cyberchondria Severity Scale for Brazilian Portuguese. AB - INTRODUCTION: The internet has proven to be a valuable resource for self-care, allowing access to information and promoting interaction between professionals, caregivers, users of health care services and people interested in health information. However, recurring searches are often related to excessive health anxiety and a phenomenon known as cyberchondria can have impacts on physical and mental health. Within this background, a Cyberchondria Severity Scale has been developed to differentiate healthy and unhealthy behavior in internet searches for health information, based on the following criteria: compulsion, distress, excesses, and trust and distrust of health professionals. OBJECTIVE: To conduct cross-cultural adaptation of the Cyberchondria Severity Scale for Brazilian Portuguese, because of the lack of an appropriate instrument for Brazil. METHODS: This study was authorized by the original author of the scale. The process was divided into the following four steps: 1) initial translation, 2) back translation, 3) development of a synthesized version, and 4) experimental application. RESULTS: Translation into Brazilian Portuguese required some idiomatic expressions to be adapted. In some cases, words were not literally translated from English into Portuguese. Only items 7, 8, 12, 23 and 27 were altered, as a means of both conforming to proper grammar conventions and achieving easy comprehension. The items were rewritten without loss of the original content. CONCLUSION: This paper presents a translated version of the Cyberchondria Severity Scale that has been semantically adapted for the Brazilian population, providing a basis for future studies in this area, which should in turn contribute to improved understanding of the cyberchondria phenomenon in this population. PMID- 27409135 TI - Family burden in schizophrenia: the influence of age of onset and negative symptoms. AB - OBJECTIVES: To investigate the determinants of family burden in a sample of patients with schizophrenia and their caregivers. METHODS: Thirty-one stable patients with schizophrenia and their main caregivers were recruited. Sociodemographic variables were assessed in a semi-structured interview, and positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed with the Schizophrenia Cognition Rating Scale (SCoRS). Levels of burden on caregivers were assessed with the Family Burden Interview Schedule (FBIS). Interactions among variables were analyzed using Pearson correlations and linear regression analysis. RESULTS: Objective and subjective FBIS scores were 1.9 (standard deviation [SD] = 0.5) and 2.4 (SD = 0.6) respectively. Objective burden correlated positively with positive and negative symptoms, and cognitive impairment. Subjective burden correlated positively with positive symptoms and negatively with mean age of disease onset. Positive, negative and cognitive symptoms accounted for 47.6% of the variance of objective burden, with negative symptoms accounting independently for 30.3%. Age of onset, parents as caregivers and positive symptoms accounted for 28% of the variance of subjective burden, with age of onset independently explaining 20.3%. CONCLUSION: Patients' clinical and sociodemographic variables are important determinants of family burden in schizophrenia. Objective burden is predicted by symptoms, particularly negative ones. Subjective burden is predicted by symptoms and sociodemographic variables, particularly age of disease onset. PMID- 27409136 TI - Phonemic verbal fluency and severity of anxiety disorders in young children. AB - INTRODUCTION: Previous studies have implicated impaired verbal fluency as being associated with anxiety disorders in adolescents. OBJECTIVES: To replicate and extend previously reported evidence by investigating whether performance in phonemic verbal fluency tasks is related to severity of anxiety symptoms in young children with anxiety disorders. We also aim to investigate whether putative associations are independent from co-occurring attention deficit hyperactivity disorder (ADHD) symptoms. METHODS: Sixty children (6-12 years old) with primary diagnoses of anxiety disorders participated in this study. Severity of symptoms was measured using clinician-based, parent-rated and self-rated validated scales. Verbal fluency was assessed using a simple task that measures the number of words evoked in 1-minute with the letter F, from which we quantified the number of isolated words, number of clusters (groups of similar words) and number of switches (transitions between clusters and/or between isolated words). RESULTS: There was a significant association between the number of clusters and anxiety scores. Further analysis revealed associations were independent from co-occurring ADHD symptoms. CONCLUSION: We replicate and extend previous findings showing that verbal fluency is consistently associated with severity in anxiety disorders in children. Further studies should explore the potential effect of cognitive training on symptoms of anxiety disorders. PMID- 27409137 TI - Semantic validation of the ISPCAN Child Abuse Screening Tools (ICAST) in Brazilian Portuguese. AB - OBJECTIVE: The International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tools (ICAST) is a battery of questionnaires created by the World Health Organization, the United Nations and ISPCAN for researching maltreatment in childhood. This study aims to translate, to adapt and to validate the semantic equivalence of all items on the three questionnaires: ICAST-C (ICAST version for Children), ICAST-R (Retrospective Interview) and ICAST-P (ICAST version for Parents). METHODS: The process of translation and semantic validation comprised five methodological steps: 1) translation; 2) back-translation; 3) correction and semantic adaptation; 4) validation of content by professional experts in the area of abuse in childhood; and 5) a study of their acceptability to a sample of the target population, using a verbal rating scale. RESULTS: In the evaluation of the expert committee, there was need to adapt several words for the Brazilian population while maintaining semantic and conceptual equivalence. In the ICAST-C acceptability study, children exhibited some difficulty understanding 7 of the items (out of 69 questions). For ICAST-P, parents reported a lack of clarity in 5 items (out of 57 questions). These issues were resolved and the Brazilian version of ICAST 3.0 was concluded. CONCLUSION: The ICAST battery is an internationally recognized tool and the process of translation into Portuguese and semantic adaptation was performed successfully. The final version proved to be easily understandable and semantic validation results were adequate. This battery has proved useful in investigation of childhood maltreatment. PMID- 27409138 TI - Effects of augmentation agents in autistic disorder patients treated with risperidone: a systematic review and a meta-analysis. PMID- 27409139 TI - Venlafaxine induced akathisia: a case report. PMID- 27409140 TI - Copper Exchange and Redox Activity of a Prototypical 8-Hydroxyquinoline: Implications for Therapeutic Chelation. AB - The N-truncated beta-amyloid (Abeta) isoform Abeta4-x is known to bind Cu(2+) via a redox-silent ATCUN motif with a conditional Kd = 30 fM at pH 7.4. This study characterizes the Cu(2+) interactions and redox activity of Abetax-16 (x = 1, 4) and 2-[(dimethylamino)-methyl-8-hydroxyquinoline, a terdentate 8-hydroxyquinoline (8HQ) with a conditional Kd(CuL) = 35 pM at pH 7.4. Metal transfer between Cu(Abeta1-16), CuL, CuL2, and ternary CuL(NIm(Abeta)) was rapid, while the corresponding equilibrium between L and Abeta4-16 occurred slowly via a metastable CuL(NIm(Abeta)) intermediate. Both CuL and CuL2 were redox-silent in the presence of ascorbate, but a CuL(NIm) complex can generate reactive oxygen species. Because the NIm(Abeta) ligand will be readily exchangeable with NIm ligands of ubiquitous protein His side chains in vivo, this class of 8HQ ligand could transfer Cu(2+) from inert Cu(Abeta4-x) to redox-active CuL(NIm). These findings have implications for the use of terdentate 8HQs as therapeutic chelators to treat neurodegenerative disease. PMID- 27409141 TI - Microbubbles with a Self-Assembled Poloxamer Shell and a Fluorocarbon Inner Gas. AB - The numerous applications of microbubbles in food science and medicine call for a better understanding and control of the effects of the properties of their shells on their stability and ability to resonate at chosen frequencies when submitted to an ultrasound field. We have investigated both millimetric and micrometric bubbles stabilized by an amphiphilic block copolymer, Poloxamer 188 (e.g., Pluronic F-68). Although Pluronic F-68 is routinely being used as a dispersing and foaming agent to facilitate phospholipid-based microbubble preparation, it has never been studied as a shell component per se. First, we investigated the adsorption kinetics of Pluronic F-68 at the interface between water and air, or air saturated with vapors of perfluorohexane (F-hexane), using bubble profile tensiometry analysis. F-Hexane was found to strongly accelerate the adsorption of Pluronic F-68 (at low concentrations) and decrease the interfacial tension values at equilibrium (at all concentrations). We also found that relatively stable microbubbles could unexpectedly be prepared from Pluronic F-68 in the absence of any other surfactant, but only when F-hexane was present. These bubbles showed an only limited volume increase over ~3 h, while a 10-fold increase in size occurred within 200 s in the absence of a fluorocarbon. Remarkably, their deflation rate decreased when the Pluronic F-68 concentration decreased, suggesting that bubbles with semidilute copolymer coverage are more stable than those more densely covered by copolymer brushes. Single-bubble experiments using laser Doppler vibratometry showed that, by contrast with other surfactant-coated microbubbles, the resonance radius of the Pluronic F-68-coated microbubbles was lower than that of naked microbubbles, meaning that they are less elastic. It was also found that the bubble's vibrational displacement amplitude decreased substantially when the microbubbles were covered with Pluronic F-68, an effect that was further amplified by F-hexane. PMID- 27409142 TI - l-Cystine Diamides as l-Cystine Crystallization Inhibitors for Cystinuria. AB - l-Cystine bismorpholide (1a) and l-cystine bis(N'-methylpiperazide) (1b) were seven and twenty-four times more effective than l-cystine dimethyl ester (CDME) in increasing the metastable supersaturation range of l-cystine, respectively, effectively inhibiting l-cystine crystallization. This behavior can be attributed to inhibition of crystal growth at microscopic length scale, as revealed by atomic force microscopy. Both 1a and 1b are more stable than CDME, and 1b was effective in vivo in a knockout mouse model of cystinuria. PMID- 27409143 TI - Multiscale Analysis for Field-Effect Penetration through Two-Dimensional Materials. AB - Gate-tunable two-dimensional (2D) materials-based quantum capacitors (QCs) and van der Waals heterostructures involve tuning transport or optoelectronic characteristics by the field effect. Recent studies have attributed the observed gate-tunable characteristics to the change of the Fermi level in the first 2D layer adjacent to the dielectrics, whereas the penetration of the field effect through the one-molecule-thick material is often ignored or oversimplified. Here, we present a multiscale theoretical approach that combines first-principles electronic structure calculations and the Poisson-Boltzmann equation methods to model penetration of the field effect through graphene in a metal-oxide-graphene semiconductor (MOGS) QC, including quantifying the degree of "transparency" for graphene two-dimensional electron gas (2DEG) to an electric displacement field. We find that the space charge density in the semiconductor layer can be modulated by gating in a nonlinear manner, forming an accumulation or inversion layer at the semiconductor/graphene interface. The degree of transparency is determined by the combined effect of graphene quantum capacitance and the semiconductor capacitance, which allows us to predict the ranking for a variety of monolayer 2D materials according to their transparency to an electric displacement field as follows: graphene > silicene > germanene > WS2 > WTe2 > WSe2 > MoS2 > phosphorene > MoSe2 > MoTe2, when the majority carrier is electron. Our findings reveal a general picture of operation modes and design rules for the 2D-materials-based QCs. PMID- 27409144 TI - o-Iodoxybenzoic Acid-Initiated One-Pot Synthesis of 4-Arylthio-1,2 naphthoquinones, 4-Arylthio-1,2-diacetoxynaphthalenes, and 5-Arylthio-/5 Aminobenzo[a]phenazines. AB - 1,2-Naphthoquiones and their derivatives constitute an important category of compounds of relevance in pharmaceutical and material chemistry. It is shown that 1,2-naphthoquinones generated by o-iodoxybenzoic acid-mediated oxidation of 2 naphthols can be subjected to a cascade of reactions, namely oxidation, Michael addition, reduction, acetylation, and cyclocondensation, in the same pot to afford diverse 4-arylthio-1,2-naphthoquinones 2, 4-arylthio-1,2 diacetoxynaphthalenes 3, and 5-arylthio-/5-aminobenzo[a]phenazines 4 in very good isolated yields. The multistep single-pot synthesis occurs smoothly in DMF at rt. PMID- 27409145 TI - Sequence-Specific Post-Synthetic Oligonucleotide Labeling for Single-Molecule Fluorescence Applications. AB - The sequence-specific fluorescence labeling of nucleic acids is a prerequisite for various methods including single-molecule Forster resonance energy transfer (smFRET) for the detailed study of nucleic acid folding and function. Such nucleic acid derivatives are commonly obtained by solid-phase methods; however, yields decrease rapidly with increasing length and restrict the practicability of this approach for long strands. Here, we report a new labeling strategy for the postsynthetic incorporation of a bioorthogonal group into single stranded regions of both DNA and RNA of unrestricted length. A 12-alkyne-etheno-adenine modification is sequence-selectively formed using DNA-templated synthesis, followed by conjugation of the fluorophore Cy3 via a copper-catalyzed azide alkyne cycloaddition (CuAAC). Evaluation of the labeled strands in smFRET measurements shows that the strategy developed here has the potential to be used for the study of long functional nucleic acids by (single-molecule) fluorescence or other methods. To prove the universal use of the method, its application was successfully extended to the labeling of a short RNA single strand. As a proof-of concept, also the labeling of a large RNA molecule in form of a 633 nucleotide long construct derived from the Saccharomyces cerevisiae group II intron Sc.ai5gamma was performed, and covalent attachment of the Cy3 fluorophore was shown with gel electrophoresis. PMID- 27409146 TI - Direct Discharges of Domestic Wastewater are a Major Source of Phosphorus and Nitrogen to the Mediterranean Sea. AB - Direct discharges of treated and untreated wastewater are important sources of nutrients to coastal marine ecosystems and contribute to their eutrophication. Here, we estimate the spatially distributed annual inputs of phosphorus (P) and nitrogen (N) associated with direct domestic wastewater discharges from coastal cities to the Mediterranean Sea (MS). According to our best estimates, in 2003 these inputs amounted to 0.9 * 10(9) mol P yr(-1) and 15 * 10(9) mol N yr(-1), that is, values on the same order of magnitude as riverine inputs of P and N to the MS. By 2050, in the absence of any mitigation, population growth plus higher per capita protein intake and increased connectivity to the sewer system are projected to increase P inputs to the MS via direct wastewater discharges by 254, 163, and 32% for South, East, and North Mediterranean countries, respectively. Complete conversion to tertiary wastewater treatment would reduce the 2050 inputs to below their 2003 levels, but at an estimated additional cost of over ?2 billion yr(-1). Management of coastal eutrophication may be best achieved by targeting tertiary treatment upgrades to the most affected near-shore areas, while simultaneously implementing legislation limiting P in detergents and increasing wastewater reuse across the entire basin. PMID- 27409147 TI - Gender Bias in the Measurement of Workaholism. AB - Past research suggests gender differences in workaholism might be due to differences in how men and women respond to the item content in workaholism measures. Using item response theory differential item functioning, we show women are less likely to report some workaholism items, leading to contamination. Specifically, women are less likely to report spending more time at work than other activities, and staying at work longer than others. We speculate that societal norms and practical restrictions on women's time results in lower endorsement rates for these items compared to men, and thus underestimates their workaholism. Results contradict past findings that men and women are similar in regard to workaholism and suggest women are in fact higher in workaholism than men. Limitations and future directions are discussed. PMID- 27409148 TI - A case of intraparotid schwannoma in a juvenile: Clinical, pathological, ultrastructural, and immunohistopathological study, including an examination of Ki-67 and MCM-3 expressions. AB - Pleomorphic adenoma, the most common benign nonvascular tumor of the parotid gland in juveniles, should be differentiated from other extremely rare tumors, including schwannoma. In this article, we present a rare case of an intraparotid schwannoma in a juvenile, along with the patient history, a description of pathological features, and the results of ultrastructural and immunohistochemical examination. The respective labeling indexes of Ki-67 and MCM-3, i.e., the mean proportions of positive tumor cells out of 1000 tumoral cells counted in 10 microscopic fields at *400 magnification, given as a percentage, were found to be 0.82% and 0.4%, respectively. PMID- 27409151 TI - The use of a portable three-lead ECG monitor to detect atrial fibrillation in general practice. AB - OBJECTIVE: To evaluate how well an inexpensive portable three-lead ECG monitor PEM identified patients with atrial fibrillation (AF) compared to a normal 12 lead ECG. DESIGN: Cross-sectional method comparison study. SETTING: From April 2014 to February 2015, we included patients coming to the general practice clinic "Laegerne Slojfen", Aalborg, Denmark for a routine ECG. Patients with severe dementia, mental illness or poor ECG readings were excluded. After oral and written informed consent an ECG and PEM recordings were obtained simultaneously. The PEM recordings were analyzed by two general practitioners (GPs) in training and ECG recordings were evaluated by a senior GP and a cardiologist. Both the PEM and the ECG recordings were analysed blinded. SUBJECTS: Ninety-three patients were included and four were excluded due to poor ECG readings. MAIN OUTCOME MEASURES: The sensitivity and specificity of PEM compared to a standard 12-lead ECG. RESULTS: Eighty-nine of the 93 (95.7%) patients had ECGs of a satisfactory technical quality and were included in the study. The sensitivity of diagnosing AF by PEM recordings was 86.7% and the specificity was 98.7% when compared to a 12-lead ECG. According to the cardiologist, the misclassification of three PEM recordings were due to interpretation errors and not related to the PEM recording per se. CONCLUSIONS: The inexpensive portable PEM device recording diagnosed AF with a high sensitivity and specificity. KEY POINTS Simple ECG monitors could be useful to identify atrial fibrillation and thereby lead to a better prevention of stroke. The PEM device was easy to use and 95.7% of the recordings were technically acceptable for detecting atrial fibrillation. The PEM device has a high sensitivity and specificity in detecting atrial fibrillation compared to a standard 12-lead ECG. Further studies should evaluate the clinical usefulness of the PEM device, e.g. to detect intermittent atrial fibrillation. PMID- 27409149 TI - MicroRNA Profiling Reveals a Role for MicroRNA-218-5p in the Pathogenesis of Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis. OBJECTIVES: To identify dysregulated miRNAs in lung tissue of patients with chronic obstructive pulmonary disease (COPD). METHODS: We performed miRNA and mRNA profiling using high throughput stem-loop reverse transcriptase quantitative polymerase chain reaction and mRNA microarray, respectively, on lung tissue of 30 patients (screening cohort) encompassing 8 never-smokers, 10 smokers without airflow limitation, and 12 smokers with COPD. Differential expression of miRNA-218-5p (miR-218-5p) was validated by reverse transcriptase quantitative polymerase chain reaction in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. MEASUREMENTS AND MAIN RESULTS: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR 218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. CONCLUSIONS: We highlight a role for miR-218-5p in the pathogenesis of COPD. PMID- 27409150 TI - Deep brain stimulation for Parkinson's disease: current status and future outlook. AB - Parkinson's disease is a neurodegenerative condition secondary to loss of dopaminergic neurons in the substantia nigra pars compacta. Surgical therapy serves as an adjunct when unwanted medication side effects become apparent or additional therapy is needed. Deep brain stimulation emerged into the forefront in the 1990s. Studies have demonstrated improvement in all of the cardinal parkinsonian signs with stimulation. Frameless and 'mini-frame' stereotactic systems, improved MRI for anatomic visualization, and intraoperative MRI-guided placement are a few of the surgical advances in deep brain stimulation. Other advances include rechargeable pulse generators, voltage- or current-based stimulation, and enhanced abilities to 'steer' stimulation. Work is ongoing investigating closed-loop 'smart' stimulation in which stimulation is predicated on neuronal feedback. PMID- 27409152 TI - Imposing limits on autonomous systems. AB - Our present era is witnessing the genesis of a sea-change in the way that advanced technologies operate. Amongst this burgeoning wave of untrammelled automation there is now beginning to arise a cadre of ever-more independent, autonomous systems. The degree of interaction between these latter systems with any form of human controller is becoming progressively more diminished and remote; and this perhaps necessarily so. Here, I advocate for human-centred and human favouring constraints to be designed, programmed, promulgated and imposed upon these nascent forms of independent entity. I am not sanguine about the collective response of modern society to this call. Nevertheless, the warning must be voiced and the issue debated, especially among those who most look to mediate between people and technology. Practitioner Summary: Practitioners are witnessing the penetration of progressively more independent technical orthotics into virtually all systems' operations. This work enjoins them to advocate for sentient, rational and mindful human-centred approaches towards such innovations. Practitioners need to place user-centred concerns above either the technical or the financial imperatives which motivate this line of progress. PMID- 27409153 TI - Toxicity and bioremediation of As(III) and As(V) in the green microalgae Botryococcus braunii: A laboratory study. AB - Worldwide threats of fuel shortages in the near future and climate change because of greenhouse gas emissions are posing severe challenges and therefore it is vital to search for sustainable ways of preventing the consequences. The dual use of microalgae for phycoremediation and biomass production for sustainable biofuel production is a viable choice. Phycoremediation of As(III) and As(V) ions using microalgae was investigated in a two-staged batch reactor. Accumulation and toxicity of inorganic arsenic forms (As(III) and As(V)) to green microalgae Botryococcus braunii depend on environmental factors. Dissolved oxygen and pH cycles did not significantly differ due to the absence or presence of arsenic (either As(III) or As(V)) ions in the culture. Monod model was utilized for representing the growth kinetics of microalgae in pure media containing various concentrations of nitrate ions. Maximum specific growth rate and saturation constant were found to be 0.14788 d-1 and 0.00105 g/L, respectively. With the increase in concentration of phosphate in growth medium, the growth of microalgae increased. Media with NaCl (1.0 g/L) and NaHCO3 (1 g/L) resulted in higher maximum biomass concentration. Effect of coexisting ions on phycoremediation of As(III) and As(V) ions using microalgae was studied. PMID- 27409155 TI - Immunoregulatory pathways following strong inflammatory processes markedly impair CD4+ T cell responses. AB - As the research and use of immunotherapies is expanding, isolating ideal combinational strategies has become the next goal for many investigators. Vaccine therapies are also becoming one of the many combinational strategies being utilized in conjunction with immunostimulatory antibodies such as checkpoint blockade or adjuvants to stimulate immune responses. Here we review aspects of the immune responses that remain to be considered for designing future targeted therapies given the recent findings of the role of out of order T cell activation signaling. Specifically, we review some considerations in generating primary T cell responses under conditions of strong immunostimulatory signals based on recent studies completed by our group and others. PMID- 27409156 TI - Acute Illness Associated with Exposure to a New Soil Fumigant Containing Dimethyl Disulfide-Hillsborough County, Florida, 2014. AB - Dimethyl disulfide (DMDS) is a new soil fumigant that is considered a replacement for methyl bromide. In 2014, the Florida Department of Health (FDOH) received several complaints of illness following a strong DMDS odor in Hillsborough County. Public health investigation of DMDS-related illness was conducted to assess illness and identify areas to target for prevention activities. This investigation included surveillance, interviews, review of medical records, review of supporting documentation, and determination of pesticide-related illness and injury case status. FDOH interviewed 66 people complaining of illness related to DMDS. Thirty-two were classified as possible and 11 as suspicious cases of DMDS-related illness. Among cases, the mean age was 48 years (range: 3 71 years). The majority were non-Hispanic (n = 43, 100%), white (n = 40, 93%), and female (n = 23, 53.5%). The most common signs and symptoms reported by exposed people included eye pain, throat irritation, nausea, dizziness, headache, and fatigue. There were 88% of cases classified as having low severity of illness and 12% classified as having moderate severity. The average distance from an application site among individuals who reported being exposed at or near their home was 0.74 miles for those classified as cases (n = 36) and 2.84 miles for those not classified as cases (n = 21, P < .05). This is the first known comprehensive report of DMDS-related illness in humans. Even though illnesses associated with DMDS in this investigation were generally of low severity, it is important to identify better ways to prevent off-target movement of DMDS and to improve notification to communities when nearby DMDS applications are planned. PMID- 27409157 TI - Validation of Turkish version of brief negative symptom scale. AB - OBJECTIVE: Negative symptoms in schizophrenia have been assessed by many instruments. However, a current consensus on these symptoms has been built and new tools, such as the Brief Negative Symptom Scale (BNSS), are generated. This study aimed to evaluate reliability and validity of the Turkish version of BNSS. METHODS: The scale was translated to Turkish and backtranslated to English. After the approval of the translation, 75 schizophrenia patients were interviewed with BNSS, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS) and Extrapyramidal Symptom Rating Scale (ESRS). Reliability and validity analyses were then calculated. RESULTS: In the reliability analysis, the Cronbach's alpha coefficient was 0.96 and item-total score correlation coefficients were between 0.655-0.884. The intraclass correlation coefficient was 0.665. The inter-rater reliability was 0.982 (p < 0.0001). In the validity analysis, the total score of BNSS-TR was correlated with PANSS Total Score, Positive Symptoms Subscale, Negative Symptoms Subscale, and General Psychopathology Subscale. CDSS and ESRS were not correlated with BNSS-TR. The factor structure of the scale was consisting the same items as in the original version. CONCLUSIONS: Our study confirms that the Turkish version of BNSS is an applicable tool for the evaluation of negative symptoms in schizophrenia. PMID- 27409154 TI - Genotype influence in responses to therapy for atrial fibrillation. AB - INTRODUCTION: Over the last decade, tremendous progress has been made in defining the genetic architecture of atrial fibrillation (AF). This has in part been driven by poor understanding of the pathophysiology of AF, limitations of current therapies and failure to target therapies to the underlying mechanisms. AREAS COVERED: Genetic approaches to AF have identified mutations encoding cardiac ion channels, and signaling proteins linked with AF and genome-wide association studies have uncovered common genetic variants modulating AF risk. These studies have provided important insights into the underlying mechanisms of AF and defined responses to therapies. Common AF-risk alleles at the chromosome 4q25 locus modulate response to antiarrhythmic drugs, electrical cardioversion and catheter ablation. While the translation of these discoveries to the bedside care of individual patients has been limited, emerging evidence supports the hypothesis that genotype-directed approaches that target the underlying mechanisms of AF may not only improve therapeutic efficacy but also minimize adverse effects. Expert commentary: There is an urgent need for randomized controlled trials that are genotype-based for the treatment of AF. Nonetheless, emerging data suggest that selecting therapies for AF that are genotype-directed may soon be upon us. PMID- 27409158 TI - Antihypertensive effects of fargesin in vitro and in vivo via attenuating oxidative stress and promoting nitric oxide release. AB - Fargesin, a bioactive neolignan isolated from magnolia plants, is widely used in the treatment of managing rhinitis, inflammation, histamine, sinusitis, and headache. To provide more biological information about fargesin, we investigated the effects of fargesin on rat aortic rings and 2-kidney, 1-clip (2K1C) hypertensive rats. In vitro, fargesin caused concentration-dependent vasorelaxation in rat isolated aortic rings induced by KCl and norepinephrine. The effect was weakened by endothelium denudation and nitric oxide (NO) synthesis inhibition. In vivo, the evolution of systolic blood pressure (SBP) was followed by weekly measurements. Angiotensin II (Ang II) and endothelin (ET) levels, NO and nitric oxide synthase (NOS), and plasma and liver oxidative stress markers were determined at the end of the experimental period. After 5 weeks of fargesin treatment, we found that fargesin treatment reduced SBP, cardiac hypertrophy, and Ang II and ET levels of hypertensive rats. Increased NOS activity and NO level were observed in fargesin-treated rats. Normalisation of plasma MDA concentrations and improvement of the antioxidant defence system in plasma and liver accompanied the antihypertensive effect of fargesin. Taken together, these results provided substantial evidences that fargesin has antihypertensive effect in 2K1C hypertensive rats via inhibiting oxidative stress and promoting NO release. PMID- 27409159 TI - Immunotherapy for oesophagogastric cancer. AB - INTRODUCTION: Gastric and oesophageal cancers are a pressing global health problem with high mortality rates and poor outcomes for advanced disease. The mainstay of treatment in the palliative setting has traditionally been chemotherapy, which accrues only modest survival benefits. As with other cancer types, there is increasing interest in the use of immunotherapy approaches to improve outcomes. AREAS COVERED: This paper reviews the aetiological and genetic characteristics of oesophagogastric (OG) cancers relevant to the application of immunotherapy and outlines the historical, present-day and potential future applications of immunotherapy in their management. EXPERT OPINION: The use of agents targeting the PD1 pathway have led to impressive and durable responses in a minority of OG cancer patients and it would be expected that combinatorial approaches with chemotherapy, radiotherapy and other biological agents will improve responses further. Identification of clinically robust biomarkers is crucial in refining such approaches moving forwards. The application of modern sequencing technology to the development of personalized neoantigen-based vaccines represents an exciting amalgamation of genomics and immunotherapy, with potentially important clinical implications in OG cancer. PMID- 27409160 TI - Metabolic control of female puberty: potential therapeutic targets. AB - INTRODUCTION: The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. AREAS COVERED: This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. EXPERT OPINION: The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress. PMID- 27409161 TI - Anaerobic digestion of spring and winter wheat: Comparison of net energy yields. AB - Anaerobic digestion of wheat was investigated under batch conditions. The article compares the potential net energy yield between a winter wheat (sown in the autumn) and a spring wheat (sown in the spring) grown in the same year and harvested at the same growth stage in the same farm. The spring wheat had a slightly higher biochemical methane potential and required lower energy inputs in cultivation, but produced a lower dry biomass yield per hectare, which resulted in winter wheat providing the best overall net energy yield. The difference was small; both varieties gave a good net energy yield. Spring sowing may also offer the opportunity for growing an additional over-winter catch crop for spring harvest, thus increasing the overall biomass yield per hectare, with both crops being potential digester feedstocks. PMID- 27409162 TI - YAP promotes erlotinib resistance in human non-small cell lung cancer cells. AB - Yes-associated protein (YAP) is a main mediator of the Hippo pathway, which promotes cancer development. Here we show that YAP promotes resistance to erlotinib in human non-small cell lung cancer (NSCLC) cells. We found that forced YAP overexpression through YAP plasmid transfection promotes erlotinib resistance in HCC827 (exon 19 deletion) cells. In YAP plasmid-transfected HCC827 cells, GTIIC reporter activity and Hippo downstream gene expression of AREG and CTGF increased significantly (P<0.05), as did ERBB3 mRNA expression (P<0.05). GTIIC reporter activity, ERBB3 protein and mRNA expression all increased in HCC827 erlotinib-resistance (ER) cells compared to parental HCC827 cells. Inhibition of YAP by small interfering RNA (siRNA) increased the cytotoxicity of erlotinib to H1975 (L858R+T790M) cells. In YAP siRNA-transfected H1975 cells, GTIIC reporter activity and downstream gene expression of AREG and CTGF decreased significantly (P<0.05). Verteporfin, YAP inhibitor had an effect similar to that of YAP siRNA; it increased sensitivity of H1975 cells to erlotinib and in combination with erlotinib, synergistically reduced migration, invasion and tumor sphere formation abilities in H1975 cells. Our results indicate that YAP promotes erlotinib resistance in the erlotinib-sensitive NSCLC cell line HCC827. Inhibition of YAP by siRNA increases sensitivity of erlotinib-resistant NSCLC cell line H1975 to erlotinib. PMID- 27409163 TI - Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases. AB - Luminal A breast cancer is the most common breast cancer subtype which is usually treated with selective estrogen receptor modulators (SERMS) like tamoxifen. Nevertheless, one third of estrogen receptor positive breast cancer patients initially do not respond to endocrine therapy and about 40% of luminal A breast tumors recur in five years. In this study, we investigated an alternative treatment approach by combining tamoxifen and salinomycin in luminal A breast cancer cell lines. We have found that salinomycin induces an additional cytotoxic effect by inhibiting the ligand independent activation of ERalpha. Thereby salinomycin increases the intracellular calcium level. This leads to a premature fusion of endosomes with lysosomes and thus to the degradation of Egfr family members. Since this process is essential for luminal A breast cancer cells to circumvent tamoxifen treatment, the combination of both drugs induces cytotoxicity in tamoxifen sensitive as well as resistant luminal A breast cancer cell lines. PMID- 27409164 TI - MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2. AB - microRNA-27a (miR-27a) is frequently dysregulated in human carcinoma, including gastric cancer. The B-cell translocation gene 2 (BTG2) has been implicated in gastric carcinogenesis. However, till now, the link between miR-27a and BTG2 in gastric cancer has not been reported. Here, we found that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer tissues and cell lines, whereas the expression level of miR-27-3p in gastric cancer was significantly higher than that of miR-27a-5p. And overexpression of miR-27a-3p, but not miR-27a-5p, markedly promoted gastric cancer cell proliferation in vitro as well as tumor growth in vivo. Further experiments revealed that BTG2 was a direct and functional target of miR-27a-3p in gastric cancer and miR-27a-3p inhibition obviously up-regulated the expression of BTG2. In turn, overexpression of BTG2 triggered G1/S cell cycle arrest, induced subsequent apoptosis, and inhibited C-myc activation following Ras/MEK/ERK signaling pathway, which involved in the biological effects of miR 27a-3p/BTG2 axis on gastric carcinogenesis and cancer progression. Overall, these results suggested that the miR-27a-3p/BTG2 axis might represent a promising diagnostic biomarker for gastric cancer patients and could be a potential therapeutic target in the management of gastric cancer. PMID- 27409165 TI - Nuclear IKKalpha mediates microRNA-7/-103/107/21 inductions to downregulate maspin expression in response to HBx overexpression. AB - Maspin is a tumor suppressor that stimulates apoptosis and inhibits metastasis in various cancer types, including hepatocellular carcinoma (HCC). Our previous study has demonstrated that HBx induced microRNA-7, 103, 107, and 21 expressions to suppress maspin expression, leading to metastasis, chemoresistance, and poor prognosis in HCC patients. However, it remains unclear how HBx elicits these microRNA expressions. HBx has been known to induce aberrant activation and nuclear translocation of inhibitor-kappaB kinase-alpha (IKKalpha) to promote HCC progression. In this study, our data further revealed that nuclear IKKalpha expression was inversely correlated with maspin expression in HBV-associated patients. Nuclear IKKalpha but not IKKbeta reduced maspin protein and mRNA expression, and inhibition of IKKalpha reverses HBx-mediated maspin downregulation and chemoresistance. In response to HBx overexpression, nuclear IKKalpha was further demonstrated to induce the gene expressions of microRNA-7, 103, -107, and -21 by directly targeting their promoters, thereby leading to maspin downregulation. These findings indicated nuclear IKKalpha as a critical regulator for HBx-mediated microRNA induction and maspin suppression, and suggest IKKalpha as a promising target to improve the therapeutic outcome of HCC patients. PMID- 27409166 TI - Comprehensive profiling and quantitation of oncogenic mutations in non small-cell lung carcinoma using single molecule amplification and re-sequencing technology. AB - Activating and resistance mutations in the tyrosine kinase domain of several oncogenes are frequently associated with non-small cell lung carcinoma (NSCLC). In this study we assessed the frequency, type and abundance of EGFR, KRAS, BRAF, TP53 and ALK mutations in tumour specimens from 184 patients with early and late stage disease using single molecule amplification and re-sequencing technology (SMART). Based on modelling of EGFR mutations, the detection sensitivity of the SMART assay was at least 0.1%. Benchmarking EGFR mutation detection against the gold standard ARMS-PCR assay, SMART assay had a sensitivity and specificity of 98.7% and 99.0%. Amongst the 184 samples, EGFR mutations were the most prevalent (59.9%), followed by KRAS (16.9%), TP53 (12.7%), EML4-ALK fusions (6.3%) and BRAF (4.2%) mutations. The abundance and types of mutations in tumour specimens were extremely heterogeneous, involving either monoclonal (51.6%) or polyclonal (12.6%) mutation events. At the clinical level, although the spectrum of tumour mutation(s) was unique to each patient, the overall patterns in early or advanced stage disease were relatively similar. Based on these findings, we propose that personalized profiling and quantitation of clinically significant oncogenic mutations will allow better classification of patients according to tumour characteristics and provide clinicians with important ancillary information for treatment decision-making. PMID- 27409167 TI - Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer. AB - Phosphoinositide (PIP) phosphatases such as myotubularins (MTMs) inhibit growth factor receptor signaling. However, the function of myotubularin-related protein 7 (MTMR7) in cancer is unknown. We show that MTMR7 protein was down-regulated with increasing tumor grade (G), size (T) and stage (UICC) in patients with colorectal cancer (CRC) (n=1786). The presence of MTMR7 in the stroma correlated with poor prognosis, whereas MTMR7 expression in the tumor was not predictive for patients' survival. Insulin reduced MTMR7 protein levels in human CRC cell lines, and CRC patients with type 2 diabetes mellitus (T2DM) or loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) had an increased risk for MTMR7 loss. Mechanistically, MTMR7 lowered PIPs and inhibited insulin-mediated AKT-ERK1/2 signaling and proliferation in human CRC cell lines. MTMR7 provides a novel link between growth factor signaling and cancer, and may thus constitute a potential marker or drug target for human CRC. PMID- 27409168 TI - Effect of perineoplasm perinephric adipose tissues on migration of clear cell renal cell carcinoma cells: a potential role of WNT signaling. AB - To investigate the cellular and molecular interactions between clear-cell renal cell carcinoma (ccRCC) and perinephric adipose tissue (PAT), perineoplasm PAT, PAT away from the neoplasm, renal sinus and subcutaneous adipose tissues were collected at the time of renal surgery for renal masses and conditioned medium (CM) was generated from 62 patients. Perineoplasm PAT CMs from 44 out of 62 (about 71%) of patients with ccRCC or benign renal diseases (e.g. oncocytomas, angiomyolipomas, multicystic kidney, interstitial fibrosis, etc.) enhanced the migration of CaKi-2 cells. Perineoplasm PAT CMs from ccRCC significantly increased migration of ACHN and CaKi-2 cells by ~8.2 and ~2.4 folds, respectively, relative to those from benign renal diseases, whereas there is no significant difference in migration between ccRCC and benign renal diseases in CMs collected from culturing PAT away from neoplasm, renal sinus and subcutaneous adipose tissues. High Fuhrman Grade was associated with increased migration of Caki-2 cells by perineoplasm PAT CMs. Perineoplasm PATs from pT3 RCCs overexpressed multiple WNTs and their CMs exhibited higher WNT/beta-catenin activity and increased the migration of Caki-2 cells compared to CMs from benign neoplasms. Addition of secreted WNT inhibitory factor-1 recombinant protein into perineoplasm PAT CMs completely blocked the cell migration. These results indicate that WNT related factors from perineoplasm PAT may promote progression of local ccRCC to locally advanced (pT3) disease by increasing ccRCC cell mobility. PMID- 27409169 TI - VPS34 regulates TSC1/TSC2 heterodimer to mediate RheB and mTORC1/S6K1 activation and cellular transformation. AB - VPS34 is reported to activate S6K1 and is implicated in regulating cell growth, the mechanisms of which remain elusive. Here, we describe novel mechanisms by which VPS34 upregulates mTOR/S6K1 activity via downregulating TSC2 protein and activating RheB activity. Specifically, upregulation of VPS34 lipid kinase increases local production of ptdins(3)p in the plasma membrane, which recruits PIKFYVE, a FYVE domain containing protein, to ptdins(3)p enriched regions of the plasma membrane, where VPS34 forms a protein complex with PIKFYVE and TSC1. This in turn disengages TSC2 from the TSC1/TSC2 heterodimer, leading to TSC2 ubiquitination and degradation. Downregulation of TSC2 promotes the activation of RheB and mTOR/S6K1. When VPS34 lipid kinase activity is increased by introduction of an H868R mutation, ptdins(3)p production at the plasma membrane is dramatically increased, which recruits more PIKFYVE and TSC1 molecules to the plasma membrane. This results in the enhanced TSC2 ubiquitination and degradation, and subsequent activation of RheB and mTORC1/S6K1, leading to oncogenic transformation. The role played by VPS34 in regulating mTOR/S6K1 activity and cellular transformation is underscored by the fact that the VPS34 kinase dead mutant blocks VPS34-induced recruitment of PIKFYVE and TSC1 to the plasma membrane. This study provides mechanistic insight into the cellular function of VPS34 in regulating oncogenic transformation and important indications for identifying VPS34 specific mutations in human cancers. PMID- 27409171 TI - Serum neuron-specific enolase levels are upregulated in patients with acute lymphoblastic leukemia and are predictive of prognosis. AB - We explored the relationship between neuron-specific enolase (NSE) levels and the clinical features of acute lymphoblastic leukemia (ALL). Seventy ALL patients and forty-two healthy controls were enrolled in this study, and their serum NSE levels were measured using an electrochemiluminescence assay. The serum NSE concentration was higher in ALL patients than in healthy controls. In ALL patients, the mean serum NSE level declined after complete remission (CR) but increased with relapse. In addition, the mean serum NSE level was lower in the CR group than in the non-CR group. High NSE levels were associated with poorer progression-free and overall survival than low NSE levels. Serum NSE levels closely correlated with several clinical features, including the immunophenotype, risk stratification and serum lactate dehydrogenase levels. Multivariate analysis revealed that high NSE expression was an independent prognostic factor in adult ALL patients. NSE mRNA levels were also higher in ALL cell lines and bone marrow mononuclear cells from ALL patients than in control cells. These results suggested that NSE could be a clinical prognostic factor and a potential therapeutic target in ALL. PMID- 27409172 TI - Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer. AB - Treatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functional consequence of induced epithelial plasticity on AR regulation during disease progression to identify factors important for treatment resistant and metastatic prostate cancer. We pinpoint the epithelial plasticity transcription factor, Snail, at the nexus of enzalutamide resistance and prostate cancer metastasis both in preclinical models of prostate cancer and in patients. In patients, Snail expression is associated with Gleason 9-10 high-risk disease and is strongly overexpressed in metastases as compared to localized prostate cancer. Snail expression is also elevated in enzalutamide-resistant prostate cancer cells compared to enzalutamide-sensitive cells, and downregulation of Snail re-sensitizes enzalutamide-resistant cells to enzalutamide. While activation of Snail increases migration and invasion, it is also capable of promoting enzalutamide resistance in enzalutamide-sensitive cells. This Snail mediated enzalutamide resistance is a consequence of increased full-length AR and AR-V7 expression and nuclear localization. Downregulation of either full-length AR or AR-V7 re-sensitizes cells to enzalutamide in the presence of Snail, thus connecting Snail-induced enzalutamide resistance directly to AR biology. Finally, we demonstrate that Snail is capable of mediating-resistance through AR even in the absence of AR-V7. These findings imply that increased Snail expression during progression to metastatic disease may prime cells for resistance to AR-targeted therapies by promoting AR activity in prostate cancer. PMID- 27409173 TI - The bile acid receptor GPBAR1 (TGR5) is expressed in human gastric cancers and promotes epithelial-mesenchymal transition in gastric cancer cell lines. AB - GPBAR1 (also known as TGR5) is a bile acid activated receptor expressed in several adenocarcinomas and its activation by secondary bile acids increases intestinal cell proliferation. Here, we have examined the expression of GPBAR1 in human gastric adenocarcinomas and investigated whether its activation promotes the acquisition of a pro-metastatic phenotype. By immunohistochemistry and RT-PCR analysis we found that expression of GPBAR1 associates with advanced gastric cancers (Stage III-IV). GPBAR1 expression in tumors correlates with the expression of N-cadherin, a markers of epithelial-mesenchymal transition (EMT) (r=0.52; P<0.01). Expression of GPBAR1, mRNA and protein, was detected in cancer cell lines, with MKN 45 having the higher expression. Exposure of MKN45 cells to GPBAR1 ligands, TLCA, oleanolic acid or 6-ECDCA (a dual FXR and GPBAR1 ligand) increased the expression of genes associated with EMT including KDKN2A, HRAS, IGB3, MMP10 and MMP13 and downregulated the expression of CD44 and FAT1 (P<0.01 versus control cells). GPBAR1 activation in MKN45 cells associated with EGF-R and ERK1 phosphorylation. These effects were inhibited by DFN406, a GPBAR1 antagonist, and cetuximab. GPBAR1 ligands increase MKN45 migration, adhesion to peritoneum and wound healing. Pretreating MKN45 cells with TLCA increased propensity toward peritoneal dissemination in vivo. These effects were abrogated by cetuximab. In summary, we report that GPBAR1 is expressed in advanced gastric cancers and its expression correlates with markers of EMT. GPBAR1 activation in MKN45 cells promotes EMT. These data suggest that GPBAR1 antagonist might have utility in the treatment of gastric cancers. PMID- 27409174 TI - High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis. AB - Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher levels of WISP1. Downregulation of WISP1 inhibited cell proliferation and invasion through increasing apoptosis and blocking cell cycle at G1 phase in CC LOVO and RKO cells. Besides, Gene set enrichment analysis (GSEA) revealed that relative genes involved in the Cell adhesion molecules and Cytokine-cytokine receptor interaction pathways were enriched in WISP1-higher expression patients. Western blot analysis showed that Cell adhesion molecules pathway associated genes (ICAM- 1, VCAM-1, SDC2 and CDH2) and Cytokine-cytokine receptor interaction pathway associated genes (VEGFC, CCL18, CXCR4 and TGFBR1) were also modulated by WISP1 downregulation. Then, we found that the protein beta-catenin was identified as a binding partner of WISP1 and mediated the functions of WISP1 through promoting cell proliferation and invasion in LOVO and RKO cells. Further in vivo tumor formation study in nude mice indicated that inhibition of WISP1 delayed the progress of tumor formation and inhibited PCNA expression. These results indicate that WISP1 could act as an oncogene and may serve as a promising therapeutic strategy for colon cancer. PMID- 27409175 TI - Induction of HOXA9 expression in three-dimensional organotypic culture of the Claudin-low breast cancer cells. AB - The gene expression signatures of the molecular intrinsic subtypes of breast cancer are regulated by epigenetic mechanisms such as methylation of CpG islands in gene promoters. Epigenetic codes can be regulated by the tumor microenvironment. The Claudin-low subtype is associated with triple-negative invasive ductal carcinomas in patients. Herein we explored epigenetic regulation of gene expression in the Claudin-low breast cancer cells by extracellular matrix (ECM), a key component of the tumor microenvironment. We modeled attachment to ECM using laminin rich ECM three-dimensional organotypic culture (lrECM 3D). In 2D and lrECM 3D cultures we examined expression of the homeobox (HOX) genes that epigenetically regulated in development and cancer. We demonstrated induction of the selected HOX genes in lrECM 3D culture of the Claudin-low breast cancer cells MDA-MB-231 and Hs578T. In particular activation of HOXA9 expression in lrECM 3D culture required binding of bromodomain containing 4 to the HOXA9 promoter and involved CpG hypomethylation. Our findings warrant further investigation of the ECM-regulated epigenetic coding of gene expression in the Claudin-low breast cancer. PMID- 27409176 TI - Synthetic low-density lipoprotein (sLDL) selectively delivers paclitaxel to tumor with low systemic toxicity. AB - Low density lipoprotein (LDL), which is a principal carrier for the delivery of cholesterol, has been used as a great candidate for the delivery of drugs to tumor based on the great requirements for cholesterol of many cancer cells. Mimicking the structure and composition of LDL, we designed a synthetic low density lipoprotein (sLDL) to encapsulate paclitaxel-alpha linolenic acid (PALA) for tumor therapy. The PALA loaded sLDL (PALA-sLDL) and PALA-loaded microemulsion (PALA-ME, without the binding domain for LDLR) displayed uniform sizes with high drug loading efficiency (> 90%). In vitro studies demonstrated PALA-sLDL exhibited enhanced cellular uptake capacity and better cytotoxicity to LDLR over expressed U87 MG cells as compared to PALA-ME. The uptake mechanisms of PALA-sLDL were involved in a receptor mediated endocytosis and macropinocytosis. Furthermore, the in vivo biodistribution and tumor growth inhibition studies of PALA-sLDL were investigated in xenograft U87 MG tumor-bearing mice. The results showed that PALA-sLDL exhibited higher tumor accumulation than PALA-ME and superior tumor inhibition efficiency (72.1%) compared to Taxol(r) (51.2%) and PALA-ME (58.8%) but with lower toxicity. These studies suggested that sLDL is potential to be used as a valuable carrier for the selective delivery of anticancer drugs to tumor with low systemic toxicity. PMID- 27409179 TI - Realistic limits for subpixel movement detection. AB - Object tracking with subpixel accuracy is of fundamental importance in many fields since it provides optimal performance at relatively low cost. Although there are many theoretical proposals that lead to resolution increments of several orders of magnitude, in practice this resolution is limited by the imaging systems. In this paper we propose and demonstrate through simple numerical models a realistic limit for subpixel accuracy. The final result is that maximum achievable resolution enhancement is connected with the dynamic range of the image, i.e., the detection limit is 1/2?(nr.bits). The results here presented may aid in proper design of superresolution experiments in microscopy, surveillance, defense, and other fields. PMID- 27409177 TI - Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation. AB - BACKGROUND: Evidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood. RESULTS: SAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no infection patients within 48h after stroke onset. NA significantly increased IL 10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing beta-arrestin2 expression which reduced the activation of the NF-kappaB pathway. Propranolol reversed this effect of NA by reducing beta-arrestin2 expression. MATERIALS AND METHODS: A systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of beta-arrestin2, NF-kappaB, IkappaBalpha and phosphor-IkappaBalpha were performed to assess the activation of the sympathetic pathway. CONCLUSION: IL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration. PMID- 27409180 TI - Tunable narrow linewidth AlGaInP semiconductor disk laser for Sr atom cooling applications. AB - We report a frequency-stabilized semiconductor disk laser based on AlGaInP and operating at 689 nm, a wavelength of interest for atomic clocks based on strontium atoms. With a gain structure designed for emission at around 690 nm, more than 100 mW of output power are generated in single-frequency operation. We show that the source can be tuned over 8 nm with pm precision. By servo-locking the frequency to the side of fringe of a reference cavity, we demonstrate rms frequency noise of 5.2 kHz. PMID- 27409181 TI - Control of evanescent field using a dynamic waveguide composed of gelatin-coated few-layer fiber. AB - We report here the results of our studies on dynamic refractive-index (RI) profile few-layer fibers in view of controlling the mode-field profile, in particular the evanescent tails under varying structural configuration. We experimentally fabricate dynamic RI profile few-layer fibers using thin gelatin coating on selectively etched fibers and illustrate how the excitation of various modes and the evanescent field at the interface can be controlled with changing humidity parameter. As a technology outcome of this research, we demonstrate through an optimized structural configuration a well performing fiber-optic high (70%-98%) relative humidity (RH) sensor with sensitivity as high as -1.07 dBm/%RH. PMID- 27409182 TI - Large-mode-area single-polarization single-mode photonic crystal fiber: design and analysis. AB - A rectangular core photonic crystal fiber structure has been presented and analyzed for single-polarization single-mode operation. Single-polarization is obtained with asymmetric design and by introducing different loss for x polarization and y-polarization of fundamental modes. Single-polarization single mode operation of the proposed photonic crystal fiber is investigated in detail by using a full vector finite element method with an anisotropic perfectly matched layer. The variations of the confinement loss and effective mode area of x-polarization and y-polarization of fundamental modes have been simulated by varying the structural parameters of the proposed photonic crystal fiber. At the optimized parameters, confinement loss and effective mode area is obtained as 0.94 dB/m and 60.67 MUm2 for y-polarization as well as 26.67 dB/m and 67.23 MUm2 for x-polarization of fundamental modes, respectively, at 1.55 MUm. Therefore simulation results confirmed that, 0.75 m length of fiber will be sufficient to get a y-polarized fundamental mode with an effective mode area as large as 60.67 MUm2. PMID- 27409178 TI - TREM-1 expression in craniopharyngioma and Rathke's cleft cyst: its possible implication for controversial pathology. AB - Whether a mixed type of craniopharyngioma (CP) exists and whether papillary craniopharyngioma (pCP) is on a histopathological continuum with Rathke's cleft cyst (RCC) remain controversial. Herein, we examined the expression and localization of beta-catenin, BRAF p.V600E (V600E), and triggering receptor expressed on myeloid cells-1 (TREM-1) in 58 samples including 20 pCPs, 26 adamantinomatous craniopharyngiomas (aCP), and 12 RCCs. Five aCPs were diagnosed with mixed type CPs and the remaining 21 cases were pure aCPs. Four of the 12 RCCs presented with significant squamous epithelium (SE). V600E immunoreactivity was observed in all pCPs in the cytoplasm, but not in the nuclei. aCPs and RCCs, including mixed type CP, did not express V600E. Nuclear beta-catenin translocation was detected exclusively in aCPs. TREM-1 was expressed in pCPs. Additionally, TREM-1 expression was detected in the SE of 5 "mixed type" CPs, while it was absent in pure aCPs. TREM-1 was expressed in 4 RCCs with SE, but not in the remaining 8 RCCs. TREM-1 mRNA levels were compared in cultured pCP and aCP cells. TREM-1 mRNA level was significantly (p < 0.001; up to 4.045 fold) higher in pCPs than in aCPs. Western blotting revealed a significantly (p < 0.001; up to 7.19 fold) lower level of TREM-1 expression in aCP cells compared to that in pCP cells. Our findings further supported that RCC and pCP may represent two ends of a morphological spectrum. A variant showing overlapping histological features of aCP and pCP should not be considered as a mixed type. PMID- 27409183 TI - Laser galvanometric scanning system for improved average power uniformity and larger scanning area. AB - A new laser galvanometric scanning optical system incorporating a dynamic-tilt focusing lens is proposed to improve the laser spot performance in adaptive manufacturing applications. The simulations focus specifically on the laser spot size, the spot profile, the spot position, the spot energy distribution, and the size of the scanning working field. It is shown that for a designed spot size of 50 MUm, the proposed system achieves an average spot size of 50.5 MUm. Moreover, the maximum position deviation of the laser beam is reduced from (x=-3.02%, y=1.30%) in a traditional scanning system to (x=-0.055%, y=0.162%) in the proposed system. Finally, the maximum working field area is increased by around 240% compared to that of a traditional system. Overall, the results show that the proposed laser galvanometric scanning system achieves a small spot size, a symmetrical and round spot profile, a uniform spot energy distribution, and a large working area. As a result, it is ideally suited to rapid prototyping applications. PMID- 27409184 TI - All-optical implementation of a time-domain ptychographic pulse reconstruction setup. AB - An all-optical implementation of pulse reconstruction using time-domain ptychography has been demonstrated showing excellent results. The implementation was easy to set up and eliminated a number of drawbacks found in other second order techniques, such as the beam splitter modifying the pulse under consideration, the time ambiguity, or the strict correspondence between time delay increment and temporal resolution. Ptychography generally offers superior performance compared to algorithms based on general projections, requires considerably less computational effort, and is much less susceptible to noise. PMID- 27409185 TI - Angular spectrum method with compact space-bandwidth: generalization and full field accuracy. AB - A recent Letter [Opt. Lett.40, 3420 (2015)OPLEDP0146-959210.1364/OL.40.003420] reported a modified angular spectrum method that uses a sampling scheme based on a compact space-bandwidth product representation. That technique is useful for focusing and defocusing propagation cases and is generalized here for the case of propagation between two defocus planes. The proposed method employs paraxial spherical phase factors and modified propagation kernels to reduce the size of the numerical space-bandwidth product needed for wave field calculations. A Wigner distribution analysis is carried out in order to ensure high accuracy of the calculations in the entire computational domain. This is achieved by analyzing the evolution of the generalized space-bandwidth product when passing through the propagation algorithm for various space-frequency constraints. The results allow the derivations of sampling criteria, and, despite this, also show that a small amount of space/frequency zero padding significantly extends the capability of the recently reported modified angular spectrum method. Simulations validate the high accuracy of that method and verify a computational and memory gain of more than two orders of magnitude when comparing this technique with the conventional angular spectrum method. PMID- 27409186 TI - Subwavelength micropolarizer in a gold film for visible light. AB - We have designed and fabricated a 100 MUm*100 MUm four-sector binary subwavelength reflecting polarization microconverter in a gold film. Using finite difference time-domain-aided numerical simulations and experiments, the micropolarizer was shown to convert an incident linearly polarized Gaussian beam of wavelength 532 nm into an azimuthally polarized beam. Conditions for generating on-axis regions of nonzero intensity when using propagating optical vortices with different initial polarization were deduced. By putting a spiral phase plate into an azimuthally polarized beam, the intensity pattern was shown to change from diffraction rings to a central peak. PMID- 27409187 TI - Dispersion engineering in nonlinear soft glass photonic crystal fibers infiltrated with liquids. AB - We present a numerical study of the dispersion characteristic modification of nonlinear photonic crystal fibers infiltrated with liquids. A photonic crystal fiber based on the soft glass PBG-08, infiltrated with 17 different organic solvents, is proposed. The glass has a light transmission window in the visible mid-IR range of 0.4-5 MUm and has a higher refractive index than fused silica, which provides high contrast between the fiber structure and the liquids. A fiber with air holes is designed and then developed in the stack-and-draw process. Analyzing SEM images of the real fiber, we calculate numerically the refractive index, effective mode area, and dispersion of the fundamental mode for the case when the air holes are filled with liquids. The influence of the liquids on the fiber properties is discussed. Numerical simulations of supercontinuum generation for the fiber with air holes only and infiltrated with toluene are presented. PMID- 27409188 TI - Rayleigh backscattering from the fundamental mode in multimode optical fibers. AB - Rayleigh backscattering produced by an incident fundamental mode in a multimode optical fiber is analyzed using a diffraction technique, with a full set of backward-propagating modes being taken into consideration. Explicit formulas are derived for mode excitation efficiency via radial distributions of the mode fields, and it is proved that only half-azimuthal modes are backscattered by the incident wave of a fixed polarization. Advanced analytical expressions are developed for fibers with a quadratic refractive-index profile, and mode groups of even numbers, composed of modes with equal propagation constants, are stated to be excited with equal efficiencies. PMID- 27409189 TI - In vivo optical interferometric imaging of human skin utilizing monochromatic light source. AB - We have demonstrated tomographic imaging of in vivo human skin with an optical interferometric imaging technique using a monochromatic light source. The axial resolution of this method is determined by the center wavelength and the NA of the objective and is irrelevant to the bandwidth of the light source in contrast to optical coherence tomography. Our imaging system is constructed with low priced and small-sized compact disk optical pickup components, a laser diode, a high NA objective, and a voice coil actuator. In spite of its low cost and small size, our imaging system can visualize the structure of human skin as clearly as a commercial reflectance confocal microscope. PMID- 27409190 TI - Wide bandwidth dual-frequency ultrasound measurements based on fiber laser sensing technology. AB - A dual-frequency ultrasound measurement system based on a distributed Bragg reflector (DBR) fiber laser sensor in a liquid medium was presented. To compare the dual-frequency measurement performance of a DBR fiber laser acoustic sensor with that of a piezoelectric (PZT) ultrasound sensor, two experiments were performed. First, we fixed the driving frequencies of two ultrasound signals at 3 and 5 MHz, and decreased the driving voltage from 15 to 3 V. The outputs of the DBR acoustic sensor show flat-balanced response to dual-frequencies, compared with the PZT acoustic sensor whose response to one of the dual-frequency signals (5 MHz in this paper) has been covered by noise at low acoustic pressure. Then we increased the acoustic pressure by fixing the driving voltage at 20 V, and changed the frequency spacing between the two ultrasound signals. By analyzing the frequency response, sensitivity, signal-to-noise ratio, and noise equivalent pressure of two acoustic sensors under different frequencies, we found that the response of the DBR sensor to wideband dual-frequency is stable, while the response of the PZT sensor deteriorates sharply with increasing frequency spacing. The results demonstrate that the DBR fiber laser sensor performs better for wide bandwidth dual-frequency ultrasound measurements. PMID- 27409191 TI - Design and experimental demonstration of electromagnetic actuation utilized on micrograting accelerometers. AB - This paper presents the design, analysis, and experimental demonstration of electromagnetic actuation utilized on micrograting accelerometers. It mainly consists of a permanent magnet and a driving coil made of three planar printed circuit board coils. A silicon movable platform and the permanent magnet with an axial magnetization of 750*103 A/m form the proof mass. The eight cantilever beams and the movable platform are made by means of the etching process, and the aluminum micrograting is fabricated by the lift-off process. Experimental data show that the electromagnetic force can reach 1.41 mN when the driving voltage is about 2.96 V. The linear operating region of the accelerometer is [-1 g,1 g] under a driving voltage of -2.8 to 2.96 V. A mean sensitivity of 2.82 V/g is obtained by three repeated feedback experiments. In addition, a linear operating region of [-2.2 g,2.2 g] is calculated when the driving voltage is [-7 V,7 V]. There is a linear relation between the driving voltage and the input acceleration. PMID- 27409192 TI - Depth measurement using structured light and spatial frequency. AB - This paper proposes a novel design of an optical system for depth measurement, adopting a computer-generated hologram to project a periodic line pattern from which a coaxial triangulation is performed. The spatial periodicity of diffraction images captured in the system is converted to the frequency domain, and the relative depth of the plane of interest is acquired. The experimental results show that the system could achieve resolution in the range of 1 mm over a relative depth range of ~300-600 mm from the camera. The standard deviations are 0.71 and 0.46 mm for two experiments. PMID- 27409193 TI - Linearly polarized Q-switched ceramic laser made with anisotropic nanostructured thin films. AB - A polarizing laser mirror was made of an alternating sequence of low and high refractive index layers of titanium oxide using glancing angle deposition (GLAD). Large refractive index contrast and large birefringence, reaching 0.5 and 0.1, respectively, could be obtained from one single raw material by changing the deposition conditions. The laser mirror could withstand a train of 2.7 ns, single mode pulses at 680 Hz, lambda=1030 nm, and peak power density of 670 MW/cm2 when used as an output coupler of a passively Q-switched (Yb0.1Y0.9)3Al5O12 ceramic laser. The polarization extinction ratio was found to be better than 30 dB both in continuous-wave and pulsed regimes. These results indicate that polarizing laser mirrors made from nanostructured thin films with GLAD, in addition to being simple to fabricate, can withstand high pulse energy density. PMID- 27409194 TI - Restoring atmospheric-turbulence-degraded images. AB - Image data experiences geometric distortions and spatial-temporal varying blur due to the strong effects of random spatial and temporal variations in the optical refractive index of the communication path. Simultaneously removing these effects from an image is a challenging task. An efficient approach is proposed in this paper to address this problem. The approach consists of four steps. First, a frame selection strategy is employed by proposing an unsupervised k-means clustering technique. Second, a B-spline-based nonrigid image registration is carried out to suppress geometric distortions. Third, a spatiotemporal kernel regression is proposed by introducing the local sharp patch concept to fuse the registered frame sequences into an image. Finally, a blind deconvolution technique is employed to deblur the fused image. Experiments are carried out with synthetic and real-world turbulence-degraded data by implementing the proposed method and two recently reported methods. The proposed method demonstrates significant improvement over the two reported methods in terms of alleviating blur and distortions, as well as improving visual quality. PMID- 27409195 TI - Random lasing at the edge of a TiO2 nanotube thin film. AB - In this paper, we introduce a random laser in which lasing action is observed at the edge of a dye-doped TiO2 thin film. A TiO2 nanotube membrane serves as a disordered structure that enhances the optical multiple scattering effect, while Rhodamine 6G dissolved in ethylene glycol is used as a gain medium. In the experiment, a random laser with a low threshold is observed when optically pumped at the fringe of a TiO2 nanotube membrane, which makes it practical for microfluidic integration. Simulation results show that multiple scattered light between the nanotubes and ethylene glycol solution is more likely to form a resonance loop with the help of a random edge structure. This well interrupted the appearance of coherent spikes in the emission laser spectrum in the experiment. The edge random laser offers simplicity and convenience in both fabrication and operation, which makes it a promising component for optofluidic laser integration with TiO2 functional material. PMID- 27409196 TI - Tunable broadband optical field enhancement in graphene-based slot waveguide at infrared frequencies. AB - Tunable broadband optical field enhancements are demonstrated for graphene-based nanoscale slot waveguides, and the extremely strong field intensity inside the slot region is produced based on the ultrahigh effective mode index. Analytic formulas are obtained to reveal the dependence of enhanced optical fields and effective mode index on the gap distance, the Fermi energy, the width of nanoribbons, and the background medium. We show that most of the optical field is concentrated within the slot regions with the normalized power about up to 86%, and the averaged optical field intensity reaches 104 MUm-2 for the slot waveguide with a 3 nm gap distance and 50 nm width. Meanwhile, the optical field enhancement effect is broadband at infrared frequencies and controlled by Fermi energy via bias electrical voltage for graphene. PMID- 27409197 TI - Modeling and analysis of distributed feedback quantum dot passively mode-locked lasers. AB - In this paper, we investigate numerically two proposed monolithic distributed feedback quantum dot passively mode-locked lasers (DFB-QDMLLs) with and without gratings in the saturable absorber (SA) section in order to enhance two important performances of QDMLLs for ultrahigh-bit-rate and single-mode applications. We find out that depending on the length of the grating, optical pulses with durations of about 3-8 ps at approximately 2nd and 4th harmonics of cavity round trip frequencies can be generated by the proposed structures. We also compare the temporal and spectral behaviors of these structures under specified bias conditions and SA lengths. It is shown that DFB-QDMLLs have the ability to generate optical pulses with more peak power than grating-embedded saturable absorber (GESA-DFB-QDMLL) structures which generate shorter pulses with narrower spectral bandwidths. We also show that DFB-QDMLLs operate in a larger range of absorber voltages while the other structure is very sensitive to absorber voltage and operates well for middle ranges of this parameter. PMID- 27409198 TI - Semi-analytical solution for the temperature profiles in solid-state laser disks mounted on heat spreaders. AB - Temperature profiles in pumped solid-state laser disks are generally calculated numerically by using finite-element programs to solve the heat conduction equation in the disk and the heat spreader. Analytical expressions exist for the longitudinal temperature profile in the case of an infinitely thick heat spreader or in the limit of zero thickness of the disk. We are presenting a simplified, semi-analytical method to calculate the three-dimensional temperature profiles for any disk or heat spreader dimensions by solving the heat conduction equation using Hankel transforms. This method allows for straightforward optimization of the cooling properties of heat-sink-mounted solid-state and semiconductor disk lasers. PMID- 27409199 TI - Application of strongly overcoupled resonant modes of long-period fiber gratings to measure the adulteration of olive oil. AB - We have shown that strongly overcoupled resonant modes of long-period fiber gratings (LPFGs) can be used to assess the adulteration of olive oil. In this background, we investigate the response characteristics of strongly overcoupled resonant modes of different orders to a surrounding medium, the refractive index (RI) of which is greater than that of the fiber cladding, and in the range where a precise refractive index measurement is immensely useful for inspecting the quality of olive oils and other edible oils. A theoretical simulation that would help in designing a sensor with suitable sensitivity and range of measurement has been presented in detail and also validated with experimental results. It was interesting to observe that in a high RI surrounding, a lower order overcoupled resonant mode is much more sensitive as compared to a higher-order one having a similar coupling coefficient. A quantitative analysis demonstrates that for a particular LPFG, the sensitivity of a strongly overcoupled LP06 mode was found to be ~2000 dB/RIU, while that of the LP07 mode having similar coupling strength was ~550 dB/RIU in the surrounding refractive index range from 1.458 to 1.520. The results have been validated experimentally. PMID- 27409200 TI - CFSpro: ray tracing for design and optimization of complex fenestration systems using mixed dimensionality approach. AB - Advanced optical ray tracing software, CFSpro, was developed for the study and optimization of complex fenestration systems (CFSs). Using an algorithm mixing 2D and 3D approaches, accurate computation of large numbers of rays in extruded geometries can be performed and visualized in real time. A thin film model was included to assess the spectral control provided by coatings. In this paper, the ray tracing model is described and validated. A novel glazing, engineered with this simulation tool, is presented. It combines the functions of daylight provision, glare protection, and seasonal thermal control while conserving a view to the outside at near normal incidence. PMID- 27409201 TI - Modulation of stimulated emission of ZnO nanowire based on electromechanical vibration. AB - An optical modulator is proposed using a double-clamped nanoelectromechanical resonator. Electromechanical-optical analysis has been performed to validate the idea. The electromechanical simulation involves the nonlocal effect as the resonator is in nanometer scale. Stimulated emission theory has been used to model the luminescence of the nanowire due to the addition of piezoelectric charges subjected to mechanical strains. Results successfully demonstrate both the intensity modulation and frequency filtering, providing an integrated solution in applications such as quantum entanglement experiments. PMID- 27409202 TI - Efficient adaptation of complex-valued noiselet sensing matrices for compressed single-pixel imaging. AB - Minimal mutual coherence of discrete noiselets and Haar wavelets makes this pair of bases an essential choice for the measurement and compression matrices in compressed-sensing-based single-pixel detectors. In this paper, we propose an efficient way of using complex-valued and nonbinary noiselet functions for object sampling in single-pixel cameras with binary spatial light modulators and incoherent illumination. The proposed method allows us to determine m complex noiselet coefficients from m+1 binary sampling measurements. Further, we introduce a modification to the complex fast noiselet transform, which enables computationally efficient real-time generation of the binary noiselet-based patterns using efficient integer calculations on bundled patterns. The proposed method is verified experimentally with a single-pixel camera system using a binary spatial light modulator. PMID- 27409203 TI - Laser scanning by rotating polarization gratings. AB - Laser beam scanning can be realized using two independently rotating, inline polarization gratings, termed Risley gratings, in a fashion similar to Risley prisms. The analytical formulas of pointing position as well as their inverse solutions are described. On this basis, the beam scanning is investigated and the performance of scanning imaging is evaluated. It is shown that the scanning function in 1D scanning evolves from a sinusoidal to triangular scan and the duty cycle increases rapidly as the ratio of grating period to wavelength is reduced toward 2. The scan pattern in 2D scanning is determined by the ratio k of the gratings' rotatory frequency. In imaging applications, when k tends toward 1 or 1, the scan pattern becomes dense and is inclined to be spiral or rose-like, respectively, which is desirable for the purpose of enhancing spatial resolution. There is a direct trade-off between spatial resolution and frame rate. The spiral and rose scanning enable multiresolution imaging, providing a preview of the scanned area in a fraction of the overall scan time, which is extremely useful for fast, real-time imaging applications. PMID- 27409204 TI - Lensless reflective point diffraction interferometer. AB - A lensless reflective point diffraction interferometer (LRPDI) is proposed for dynamic wavefront measurement. The point diffraction interferometer is integrated on a small substrate with properly designed thin film, which is used for generating the interferogram with high carrier frequency at a CCD target. By lensless imaging, the complex amplitude at the CCD target can be propagated to the conjugated plane of the exit pupil of an incident wavefront, which not only avoids the edge diffraction in the interferogram, but also eliminates systematic error. The accuracy of LRPDI is demonstrated by simulation and experiment, and a precision better than 1/150 wavelength is achieved. The new design with lensless imaging processing is suitable for dynamic wavefront measurement. PMID- 27409205 TI - Beam distortion of rotation double prisms with an arbitrary incident angle. AB - The distortion of beam shape in rotation Risley prisms is discussed in this paper. Using the ray-tracing method based on vector refraction theorem, a rigorous theoretical model of beam distortion with an arbitrary incident angle is established to explore the influencing factors. For a specified double-prism pair, the emergent beam is squeezed in one direction while stretched in the mutual perpendicular direction, the distortion of which is determined by the relative rotation angle. Moreover, the distortion of beam shape is greatly influenced by the wedge angles and the refractive indices of the prisms, as well as different double-prism configurations, while uncorrelated to the prism thickness and the distance between two prisms. This paper demonstrates the regular change of the beam shape with multiparameter variations in rotation double prisms, which can be applied to the design of rotation double-prism systems. PMID- 27409206 TI - Target-in-the-loop remote sensing of laser beam and atmospheric turbulence characteristics. AB - A new target-in-the-loop (TIL) atmospheric sensing concept for in situ remote measurements of major laser beam characteristics and atmospheric turbulence parameters is proposed and analyzed numerically. The technique is based on utilization of an integral relationship between complex amplitudes of the counterpropagating optical waves known as overlapping integral or interference metric, whose value is preserved along the propagation path. It is shown that the interference metric can be directly measured using the proposed TIL sensing system composed of a single-mode fiber-based optical transceiver and a remotely located retro-target. The measured signal allows retrieval of key beam and atmospheric turbulence characteristics including scintillation index and the path integrated refractive index structure parameter. PMID- 27409207 TI - Quantitative phase imaging using transport of intensity equation with multiple bandpass filters. AB - A phase imaging based on the transport of intensity equation using multiple bandpass filters is proposed. The proposed method enables us to measure a phase distribution quantitatively from through-focus intensity images obtained by using a white light source and multiple bandpass filters. The technique improves the accuracy of a phase measurement by increasing the number of intensity images obtained at different defocused positions. The feasibility of the phase measurement and the improvement in the accuracy with the increasing the through focus images are confirmed by numerical simulations and optical experiments. PMID- 27409208 TI - Limits imposed by nonlinear coupling on rotation sensitivity of a semiconductor ring laser gyroscope. AB - The sensitivity of a monolithically integrated semiconductor ring laser gyro is severely limited by the high value of the lock-in threshold. In this work, we calculate the lock-in threshold using perturbation theory and coupled mode theory analysis. It is shown that gyro sensitivity is limited to an input rotation rate of 108 deg / h due to nonlinear coupling between the countertraveling modes. This coupling arises due to the backreflection of modes from moving index gratings, induced by rotation. Lock-in threshold is directly proportional to the strength of nonlinear coupling and spatial overlap of the modes' energy densities with periodic index perturbations. PMID- 27409209 TI - Implementation of a long range, distributed-volume, continuously variable turbulence generator. AB - We have constructed a 180-m-long distributed, continuously variable atmospheric turbulence generator to study high-power laser beam propagation. This turbulence generator operates on the principle of free convection from a heated surface placed below the entire propagation path of the beam, similar to the situation in long-distance horizontal propagation for laser communications, power beaming, or directed energy applications. The turbulence produced by this generator has been characterized through constant-temperature anemometry, as well as by the scintillation of a low-power laser beam. PMID- 27409210 TI - Compressive sensing spectroscopy with a single pixel camera. AB - Spectrometry requires high spectral resolution and high photometric precision while also balancing cost and complexity. We address these requirements by employing a compressive-sensing camera capable of improving signal acquisition speed and sensitivity in limited signal scenarios. In particular, we implement a fast single pixel spectrophotometer with no moving parts and measure absorption and emission spectra comparable with commercial products. Our method utilizes Hadamard matrices to sample the spectra and then minimizes the total variation of the signal. The experimental setup includes standard optics and a grating, a low cost digital micromirror device, and an intensity detector. The resulting spectrometer produces a 512 pixel spectrum with low mean-squared error and up to a 90% reduction in data acquisition time when compared with a standard spectrophotometer. PMID- 27409211 TI - Highly efficient reflective Dammann grating with a triangular structure. AB - A highly efficient reflective Dammann grating with a triangular structure operating at 1064 nm wavelength under normal incidence for TE polarization is designed and fabricated. Rigorous coupled wave analysis and particle swarm optimization algorithms are adopted to design and analyze the properties. The triangular reflective grating could cancel the 0th order, and the mechanism is clarified by the simplified modal method. The gratings are fabricated by direct laser writing lithography. The diffraction efficiency of fabricated grating is more than 86% at 1064 nm wavelength (97.6% in theory). This reflective grating should be a useful optical element in the field of high-power lasers as well as other reflective applications. PMID- 27409212 TI - Four-zone varifocus mirrors with adaptive control of primary and higher-order spherical aberration. AB - Electrostatically actuated deformable mirrors with four concentric annular electrodes can exert independent control over defocus as well as primary, secondary, and tertiary spherical aberration. In this paper we use both numerical modeling and physical measurements to characterize recently developed deformable mirrors with respect to the amount of spherical aberration each can impart, and the dependence of that aberration control on the amount of defocus the mirror is providing. We find that a four-zone, 4 mm diameter mirror can generate surface shapes with arbitrary primary, secondary, and tertiary spherical aberration over ranges of +/-0.4, +/-0.2, and +/-0.15 MUm, respectively, referred to a non normalized Zernike polynomial basis. We demonstrate the utility of this mirror for aberration-compensated focusing of a high NA optical system. PMID- 27409213 TI - Single-shot absolute 3D shape measurement with Fourier transform profilometry. AB - Fourier transform profilometry (FTP) is one of the frequently adopted three dimensional (3D) shape measurement methods due to its ability to recover single shot 3D shapes, yet it is challenging to retrieve the absolute phase map solely from one single grayscale fringe image. This paper presents a computational framework that overcomes this limitation of FTP with digital fringe projection (DFP). By using geometric constraints, an absolute phase map can be retrieved point-by-point from one single grayscale fringe image. Experiments demonstrate the success of our proposed framework with single-shot absolute 3D shape measurement capability. PMID- 27409214 TI - Effects of surface materials on polarimetric-thermal measurements: applications to face recognition. AB - Materials, such as cosmetics, applied to the face can severely inhibit biometric face-recognition systems operating in the visible spectrum. These products are typically made up of materials having different spectral properties and color pigmentation that distorts the perceived shape of the face. The surface of the face emits thermal radiation, due to the living tissue beneath the surface of the skin. The emissivity of skin is approximately 0.99; in comparison, oil- and plastic-based materials, commonly found in cosmetics and face paints, have an emissivity range of 0.9-0.95 in the long-wavelength infrared part of the spectrum. Due to these properties, all three are good thermal emitters and have little impact on the heat transferred from the face. Polarimetric-thermal imaging provides additional details of the face and is also dependent upon the thermal radiation from the face. In this paper, we provide a theoretical analysis on the thermal conductivity of various materials commonly applied to the face using a metallic sphere. Additionally, we observe the impact of environmental conditions on the strength of the polarimetric signature and the ability to recover geometric details. Finally, we show how these materials degrade the performance of traditional face-recognition methods and provide an approach to mitigating this effect using polarimetric-thermal imaging. PMID- 27409215 TI - Effects of anisotropic turbulence on average polarizability of Gaussian Schell model quantized beams through ocean link. AB - Based on the spatial power spectrum of the refractive index of anisotropic turbulence, the average polarizability of the Gaussian Schell-model quantized beams and lateral coherence length of the spherical wave propagating through the ocean water channel are derived. Numerical results show that, in strong temperature fluctuation, the depolarization effects of anisotropic turbulence are inferior to isotropic turbulence, as the other parameters of two links are the same. The depolarization effects of salinity fluctuation are less than the effects of the temperature fluctuation; the average polarizability of beams increases when increasing the inner scale of turbulence and the source's transverse size; and the larger rate of dissipation of kinetic energy per unit mass of fluid enhances the average polarizability of beams. The region of the receiving radius is smaller than the characteristic radius and the average polarizability of beams in isotropy turbulence is smaller than that of beams in anisotropy turbulence. However, the receiving radius region is larger than a characteristic radius and the average polarizability of beams in isotropy turbulence is larger than that of beams in anisotropy turbulence. PMID- 27409216 TI - Imprinting high-gradient topographical structures onto optical surfaces using magnetorheological finishing: manufacturing corrective optical elements for high power laser applications. AB - Corrective optical elements form an important part of high-precision optical systems. We have developed a method to manufacture high-gradient corrective optical elements for high-power laser systems using deterministic magnetorheological finishing (MRF) imprinting technology. Several process factors need to be considered for polishing ultraprecise topographical structures onto optical surfaces using MRF. They include proper selection of MRF removal function and wheel sizes, detailed MRF tool and interferometry alignment, and optimized MRF polishing schedules. Dependable interferometry also is a key factor in high gradient component manufacture. A wavefront attenuating cell, which enables reliable measurement of gradients beyond what is attainable using conventional interferometry, is discussed. The results of MRF imprinting a 23 MUm deep structure containing gradients over 1.6 MUm / mm onto a fused-silica window are presented as an example of the technique's capabilities. This high-gradient element serves as a thermal correction plate in the high-repetition-rate advanced petawatt laser system currently being built at Lawrence Livermore National Laboratory. PMID- 27409217 TI - Photometric correction for an optical CCD-based system based on the sparsity of an eight-neighborhood gray gradient. AB - In an optical measurement and analysis system based on a CCD, due to the existence of optical vignetting and natural vignetting, photometric distortion, in which the intensity falls off away from the image center, affects the subsequent processing and measuring precision severely. To deal with this problem, an easy and straightforward method used for photometric distortion correction is presented in this paper. This method introduces a simple polynomial fitting model of the photometric distortion function and employs a particle swarm optimization algorithm to get these model parameters by means of a minimizing eight-neighborhood gray gradient. Compared with conventional calibration methods, this method can obtain the profile information of photometric distortion from only a single common image captured by the optical CCD-based system, with no need for a uniform luminance area source used as a standard reference source and relevant optical and geometric parameters in advance. To illustrate the applicability of this method, numerical simulations and photometric distortions with different lens parameters are evaluated using this method in this paper. Moreover, the application example of temperature field correction for casting billets also demonstrates the effectiveness of this method. The experimental results show that the proposed method is able to achieve the maximum absolute error for vignetting estimation of 0.0765 and the relative error for vignetting estimation from different background images of 3.86%. PMID- 27409218 TI - Investigation of a broadband refractory metal metamaterial absorber at terahertz frequencies. AB - A broadband, polarization-independent, and wide-angle refractory metal metamaterial absorber is numerically investigated at terahertz frequencies, which consists of a periodic array of a chromium metallic loop and a chromium metallic film separated by a polyimide layer. Results show that a higher than 90% broadband absorption can be achieved for the range of frequencies from 1.00 through 2.43 THz, and the full absorption width at half-maximum can attain 110.80%, which is considerably larger than in previously reported results. Moreover, the greater than 90% broadband absorption response can still be maintained when the incidence angle increases to 45 degrees . The physical origin of the proposed broadband absorber originates from localized surface plasmon resonances of the single metallic loop resonator. Furthermore, the designed concept also can be achieved in the visible and near-infrared region by rationally designing the dimensions of the absorber. This compact design has potential applications in stealth technology, energy harvesting, and thermal imaging. PMID- 27409219 TI - Beam propagation of efficient frequency-doubled optical vortices. AB - Frequency doubling of optical vortices is demonstrated with an optical-optical efficiency exceeding 70%, using a spiral phase plate at a fundamental vortex energy of 10.6 mJ. Beam propagation of the doubled vortex output is also investigated both experimentally and theoretically. Spatial transforms in the output during propagation are observed. PMID- 27409220 TI - Effect of photometric detector spectral response quality on white LED spectral mismatch correction factors. AB - Light-emitting-diode (LED)-based solid-state lighting has become a real option for private and public lighting after achieving high total luminous flux (TLF) and luminous efficacy levels, thus promoting the development of energy efficient use regulation to be fulfilled by LED lamps and LED luminaires. Here, we propose a photometer-quality-based fast-checking criterion. This allows photometric technicians to perform a quick evaluation of the photometric head spectral response quality effect on the LED source spectral mismatch correction factor when determining the TLF and luminous efficacy minimum approved levels performance parameters subject to mandatory verification by the conformity assessment procedures technically supporting the corresponding regulation. The proposed criterion applies for a wide range of photometric detector heads' qualities (2.6%<=f1'<=36.4%). PMID- 27409221 TI - Reflectance and fluorescence characterization of maize species using field laboratory measurements and lidar remote sensing. AB - Laser-induced fluorescence is an important technique to study photosynthesis and plants. Information on chlorophyll and other pigments can be obtained. We have been using a mobile laboratory in a Chinese experimental farm setting to study maize (Zea mays L.) leaves by reflectance and fluorescence measurements and correlated the spectroscopic signals to the amount of fertilizer supplied. Further, we studied five different species of maize using the remote monitoring of the fluorescence signatures obtained with the same mobile laboratory, but now in a laser radar remote-sensing configuration. The system separation from the target area was 50 m, and 355 nm pulsed excitation using the frequency-tripled output from an Nd:YAG laser was employed. Principal component analysis and linear discriminant analysis were combined to identify the different maize species using their fluorescence spectra. Likewise, the spectral signatures in reflectance and fluorescence frequently allowed us to separate different fertilizer levels applied to plants of the same species. PMID- 27409222 TI - Solid, good, and great program managers/principal investigators: editorial. AB - Editor-in-Chief Ron Driggers provides suggestions on how to become a successful program manager or principal investigator. PMID- 27409223 TI - An Innovative Intra-articular Osteotomy in the Treatment of Posterolateral Tibial Plateau Fracture Malunion. AB - Posterolateral tibial plateau fractures are not uncommon and the diagnosis can be easily missed. The treatment is technically demanding, which can easily lead to malunion of the posterolateral tibial plateau fracture. Here, we describe an innovative intra-articular osteotomy for the treatment of posterolateral tibial plateau fracture malunion. From 2010 through 2012, 13 patients with a posterolateral tibial plateau fracture malunion were treated in our trauma center. The patients were referred because of instability or knee pain. The instability was confirmed by physical examinations preoperatively. The depression malunion and lower limb alignment were evaluated on X-rays and computed tomography scans. All posterolateral tibial plateau fracture malunions were treated with an innovative intra-articular osteotomy via an extended anterolateral approach. The mean follow-up was 19.6 months (range, 14-28 months). The posterolateral osteotomy healed at an average of 15.1 weeks. The depression malunion was corrected in all patients, which was from 15.4 mm preoperatively to 3.3 mm at 12 months postoperatively. The average Lysholm, Knee Society Score, and visual analog scale scores were 91.7, 92.5, and 0.5, respectively. No loss of reduction, nonunion, or wound infection was observed. An innovative intra articular osteotomy via an extended anterolateral approach is an effective treatment for posterolateral tibial plateau fracture malunion. The treatment achieved satisfactory functional results and knee stability restoration. PMID- 27409225 TI - Phytotherapy in reducing glycemic index and testicular oxidative stress resulting from induced diabetes: a review. AB - Oxidative stress plays a main role in the development of diabetes complications. The impairment of gonadal antioxidant potential and endocrine disturbance in diabetic males causes testicular damage and failure in sperm production. Plants have been widely used to control diabetes due their hypoglycemic and antioxidant potential, contributing towards the recovery of testicular function. Current study comprises a review of the literature on the main medicinal plants used in the recovery of testicular oxidative damage in animals with experimental diabetes. Eighteen plant species in the nineteen studies selected from the search strategy were evaluated. Plant extracts were evaluated according to their effects on blood glucose and insulin levels, antioxidant enzymes and oxidant levels, lipid peroxidation, total protein, testosterone levels, gonadosomatic index, diameter of seminiferous tubules, seminiferous epithelium height and integrity, number of germ cells at stage VII and apoptosis in the seminiferous epithelium, sperm production, motility, viability and morphology. After the analysis of the studies, it was observed that plant species, used alone or in combination, may control testicular oxidative damage triggered by diabetes. The antioxidant potential varies among species, with some plants proving to have a better performance in the recovery of reproduction parameters than others. PMID- 27409224 TI - Effects of flooding stress in 'Micro-Tom' tomato plants transformed with different levels of mitochondrial sHSP23.6. AB - Soil flooding is an environmental stressor for crops that can affect physiological performance and reduce crop yields. Abiotic stressors cause changes in protein synthesis, modifying the levels of a series of proteins, especially the heat shock proteins (HSP), and these proteins can help protect the plants against abiotic stress. The objective of this study was to verify if tomato plants cv. Micro-Tom from different genotypes with varying expression levels of MT-sHSP23.6 (mitochondrial small heat shock proteins) have different responses physiological to flooding. Plants from three genotypes (untransformed, MT sHSP23.6 sense expression levels and MT-sHSP23.6 antisense expression levels) were cultivated under controlled conditions. After 50 days, the plants were flooded for 14 days. After this period half of the plants from each genotype were allowed to recover. Chlorophyll fluorescence, gas exchange, chlorophyll index, leaf area and dry matter were evaluated. Flood stress affected the photosynthetic electron transport chain, which is related to inactivation of the oxygen-evolving complex, loss of connectivity among units in photosystem II, oxidation-reduction of the plastoquinone pool and activity of photosystem I. The genotype with MT sHSP23.6 sense expression levels was less sensitive to stress from flooding. PMID- 27409226 TI - Cotylogaster basiri Siddiqi & Cable, 1960 (Aspidobothrea: Aspidogastridae) in Pogonias cromis (Linnaeus, 1766) (Perciformes: Sciaenidae): first report from Brazil. AB - Up until now, there have been few studies of the helminth fauna of Brazilian populations of Pogonias cromis. In North America, P. cromis is known to be a definitive host of Cotylogaster basiri, although there have been no reports of any species of Cotylogaster infecting fish in Brazil. During necropsies of marine fish obtained from professional fisherman in the state of Rio Grande do Sul, Brazil, specimens of C. basiri were found in the intestine and rectum of P. cromis. In comparison with previous studies, differences were found in relation to the number of lobes in the buccal disc and the development of the biocellate larvae in the eggs of C. basiri. This is the first report of C. basiri in P. cromis from Brazil, contributing to the understanding of the helminth fauna of this fish from the coastal zone of Brazil. PMID- 27409227 TI - Death of pastures syndrome: tissue changes in Urochloa hybrida cv. Mulato II and Urochloa brizantha cv. Marandu. AB - The quality of forage production is a prerequisite to raising livestock. Therefore, income losses in this activity, primarily cattle raising, can result in the impossibility of economic activity. Through the qualitative and quantitative anatomical study of Urochloa hybrida cv. Mulato II and U. brizantha cv. Marandu, we searched for descriptions and compared changes in the individual vegetative body from populations with death syndrome pastures (DPS). Specimens were collected at different physiological stages from farms in northern Mato Grosso. After collection, the individuals were fixed in FAA50 and stored in 70% alcohol. Histological slides were prepared from the middle third of the sections of roots, rhizomes, and leaves, and the proportions and characteristics of tissues were evaluated in healthy, intermediate, and advanced stages of DPS. Changes were compared between cultivars. With the advancement of the syndrome, the following changes were observed: a more marked decrease in the length of roots in U. hybrida; disorganization of the cortical region of the roots and rhizome cultivars; fungal hyphae in roots and aerenchyma formation in U. hybrida; a decrease in sclerenchyma fiber proportions in roots and leaves; sclerification of the epidermis of U. brizantha rhizomes; and an increase in pericyclic fibers in U. hybrida. Furthermore, there was a decrease in the volume of epidermal cells of the abaxial face of the leaves of both cultivars, with a greater reduction in U. hybrida; a gradual decrease in thickness in the midrib of leaves similar to leaf mesophyll; conduction system obstructions; partial or total cell lysis in roots and rhizomes affected by the syndrome. Obstructions in sieve tube element and companion cells, and sometimes obstruction in xylem vessel elements. The evolution of DPS in cultivars was similar, but there were variations, arising probably from the physiological response to stress, such as aerenchyma formation in the root and increased pericycle in the rhizome of U. hybrida. PMID- 27409228 TI - Distribution and fluctuations of backswimmers (Notonectidae) in a tropical shallow lake and predation on microcrustaceans. AB - Notonectids are widely distributed in freshwaters and can prey on zooplankton in temperate lakes. However, its role in structuring the zooplankton community is unknown in tropical lakes. Thus, our objective was to study the notonectid Martarega uruguayensis in a Brazilian tropical shallow lake to evaluate its potential as a zooplankton predator. Its horizontal distribution was analized in the lake throughout one year in fortnightly samplings. Backswimmers were more abundant (mean density 162.9 +/- 25.8 ind.m-2) in the cool-dry season, with a strong preference by the littoral zone (mean density 139.9 +/- 17.5 ind.m-2). Laboratory experiments were undertaken with young and adult notonectid and the two most abundant cladocerans, Daphnia gessneri and Ceriodaphnia richardi, as prey. Predation by backswimmers in the laboratory showed that only juveniles fed on microcrustaceans (mean ingestion rate of 1.2 +/- 0.2 Daphnia and 1.0 +/- 0.2 Ceriodaphnia per predator per hour), without size selectivity. Adult insects probably have difficulties in detecting and manipulating small planktonic organisms. On the other hand, young instars might influence zooplankton community, especially in the littoral zone of the lake. This study does contribute to a better understanding of trophic interactions in tropical shallow lakes and is the first to investigate the predation of a notonectid on microcrustaceans from Lake Monte Alegre. PMID- 27409229 TI - Midgut of the diplopod Urostreptus atrobrunneus: structure, function, and redefinition of hepatic cells. AB - Diplopods are considered important macroarthropods the soil as part of its maintenance and balance. These animals usually do not occur in high densities, but population explosions caused by environmental disturbances, climate changes, and use of pesticides that eliminate possible competitors, have been reported. The millipede Urostreptus atrobrunneus Pierozzi and Fontanetti, 2006 have become a nuisance to humans in infestation sites in urban centers of the state of Sao Paulo, Brazil. As a contribution to the understanding of this potential pest, this study describes the histology, histochemistry, and ultrastructure of the U. atrobrunneus midgut, and presents the redefinition of hepatic cells somewhat controversial in the literature. The region of the midgut is characterized by the absence of a cuticular intima, and composed of a pseudostratified epithelium on a thick basal membrane, followed by a muscle layer, a layer of hepatic cells, lined by an external membrane. The morphology observed in U. atrobrunneus is similar to that reported for other species of diplopods. The hepatic cells have been previously described as randomly without forming a layer, however, the present results clearly demonstrate that these cells form a continuous layer over the whole midgut. PMID- 27409230 TI - Reproductive parameters of Phytoseiulus macropilis (Banks) fed with Tetranychus urticae Koch (Acari: Phytoseiidae, Tetranychidae) in laboratory. AB - Predatory mites that belong to the Phytoseiidae family are one of the main natural enemies of phytophagous mites, thus allowing for their use as a biological control. Phytoseiulus macropilis (Banks, 1904) (Acari: Phytoseiidae) is among the main species of predatory mites used for this purpose. Tetranychus urticae Koch, 1836 (Acari: Tetranychidae) is considered to be one of the most important species of mite pests and has been described as attacking over 1,100 species of plants in 140 families with economic value. The objective of the present study was to investigate, in the laboratory, the reproductive parameters of the predatory mite P. macropilis when fed T. urticae. Experiments were conducted under laboratory conditions at 25 +/- 2 degrees C of temperature, 70 +/- 10% RH and 14 hours of photophase. In addition, biological aspects were evaluated and a fertility life table was established. The results of these experiments demonstrated that the longevity of adult female was 27.5 days and adult male was 29.0 days. The population was estimated to increase approximately 27 times (Ro) in mean generation time (T), which was 17.7 days. Lastly, the mite population grew 1.2 times/day (lambda) and doubled every 3.7 days (TD). PMID- 27409231 TI - Ecomorphological correlates of twenty dominant fish species of Amazonian floodplain lakes. AB - Fishes inhabiting Amazonian floodplain lakes exhibits a great variety of body shape, which was a key advantage to colonize the several habitats that compose these areas adjacent to the large Amazon rivers. In this paper, we did an ecomorphological analysis of twenty abundant species, sampled in May and August 2011, into two floodplain lakes of the lower stretch of the Solimoes River. The analysis detected differences among species, which could be probably associated with swimming ability and habitat use preferences. PMID- 27409232 TI - Focus on Surgical Outcomes That Matter to Older Patients. PMID- 27409233 TI - Disease surveillance of Atlantic herring: molecular characterization of hepatic coccidiosis and a morphological report of a novel intestinal coccidian. AB - Surveillance for pathogens of Atlantic herring, including viral hemorrhagic septicemia virus (VHSV), Ichthyophonus hoferi, and hepatic and intestinal coccidians, was conducted from 2012 to 2016 in the NW Atlantic Ocean, New Jersey, USA. Neither VHSV nor I. hoferi was detected in any sample. Goussia clupearum was found in the livers of 40 to 78% of adult herring in varying parasite loads; however, associated pathological changes were negligible. Phylogenetic analysis based on small subunit 18S rRNA gene sequences placed G. clupearum most closely with other extraintestinal liver coccidia from the genus Calyptospora, though the G. clupearum isolates had a unique nucleotide insertion between 604 and 729 bp that did not occur in any other coccidian species. G. clupearum oocysts from Atlantic and Pacific herring were morphologically similar, though differences occurred in oocyst dimensions. Comparison of G. clupearum genetic sequences from Atlantic and Pacific herring revealed 4 nucleotide substitutions and 2 gaps in a 1749 bp region, indicating some divergence in the geographically separate populations. Pacific G. clupearum oocysts were not directly infective, suggesting that a heteroxenous life cycle is likely. Intestinal coccidiosis was described for the first time from juvenile and adult Atlantic herring. A novel intestinal coccidian species was detected based on morphological characteristics of exogenously sporulated oocysts. A unique feature in these oocysts was the presence of 3 long (15.1 +/- 5.1 um, mean +/-SD) spiny projections on both ends of the oocyst. The novel morphology of this coccidian led us to tentatively name this parasite G. echinata n. sp. PMID- 27409234 TI - Occurrence of salmonid alphavirus (SAV) and piscine orthoreovirus (PRV) infections in wild sea trout Salmo trutta in Norway. AB - Viral diseases represent a serious problem in Atlantic salmon (Salmo salar L.) farming in Norway. Pancreas disease (PD) caused by salmonid alphavirus (SAV) and heart and skeletal muscle inflammation (HSMI) caused by piscine orthoreovirus (PRV) are among the most frequently diagnosed viral diseases in recent years. The possible spread of viruses from salmon farms to wild fish is a major public concern. Sea trout S. trutta collected from the major farming areas along the Norwegian coast are likely to have been exposed to SAV and PRV from farms with disease outbreaks. We examined 843 sea trout from 4 counties in Norway for SAV and PRV infections. We did not detect SAV in any of the tested fish, although significant numbers of the trout were caught in areas with frequent PD outbreaks. Low levels of PRV were detected in 1.3% of the sea trout. PRV-infected sea trout were caught in both salmon farming and non-farming areas, so the occurrence of infections was not associated with farming intensity or HSMI cases. Our results suggest that SAV and PRV infections are uncommon in wild sea trout. Hence, we found no evidence that sea trout are at risk from SAV or PRV released from salmon farms. PMID- 27409235 TI - Incidence of antimicrobial-resistance genes and integrons in antibiotic-resistant bacteria isolated from eels and aquaculture ponds. AB - The overuse of antimicrobials in aquaculture has promoted the selection of antimicrobial-resistant bacteria. Here we investigated the abundance of antimicrobial-resistance genes and integrons in 108 strains of antibiotic resistant bacteria isolated from eels and aquaculture ponds in China. Conventional PCR was implemented to examine common antibiotic-resistance genes, integrons, and their gene cassette arrays. The results showed that the antibiotic resistance genes blaTEM, tetC, sulI, aadA, floR, and qnrB were detected at high percentages, as were a number of other resistance genes. Class I integrons were present in 79.63% of the strains, and 10 out of 108 isolates carried class II integrons. Class III integrons were not detected. Three strains carried both class I and class II integrons, and 73.26% of the class I integron-positive isolates contained the qacEDelta1/sul1 gene. Fourteen types of integron cassette arrays were found among class I integron-positive isolates. A new array, dfrB4 catB3-blaOXA-10-aadA1, was discovered in this study. The gene cassette array dfrA12-orfF-aadA2 was the most widely distributed. In summary, 23 different gene cassettes encoding resistance to 8 classes of antibiotics were identified in the class I integrons, and the main cassettes contained genes encoding resistance to aminoglycosides (aad) and trimethoprim (dfr). All class II integron-positive strains had only a single gene cassette array, viz. dfrA1-catB2-sat2-aadA1. High levels of antimicrobial-resistance genes and integrons in eels and auqauculture ponds suggest that the overuse of antimicrobials should be strictly controlled and that the levels of bacterial antimicrobial-resistance genes in aquaculture should be monitored. PMID- 27409236 TI - Ichthyophonus parasite phylogeny based on ITS rDNA structure prediction and alignment identifies six clades, with a single dominant marine type. AB - Despite their widespread, global impact in both wild and cultured fishes, little is known of the diversity, transmission patterns, and phylogeography of parasites generally identified as Ichthyophonus. This study constructed a phylogeny based on the structural alignment of internal transcribed spacer (ITS) rDNA sequences to compare Ichthyophonus isolates from fish hosts in the Atlantic and Pacific oceans, and several rivers and aquaculture sites in North America, Europe, and Japan. Structure of the Ichthyophonus ITS1-5.8S-ITS2 transcript exhibited several homologies with other eukaryotes, and 6 distinct clades were identified within Ichthyophonus. A single clade contained a majority (71 of 98) of parasite isolations. This ubiquitous Ichthyophonus type occurred in 13 marine and anadromous hosts and was associated with epizootics in Atlantic herring, Chinook salmon, and American shad. A second clade contained all isolates from aquaculture, despite great geographic separation of the freshwater hosts. Each of the 4 remaining clades contained isolates from single host species. This study is the first to evaluate the genetic relationships among Ichthyophonus species across a significant portion of their host and geographic range. Additionally, parasite infection prevalence is reported in 16 fish species. PMID- 27409237 TI - Experimental inoculation of Louisiana red swamp crayfish Procambarus clarkii with white spot syndrome virus (WSSV). AB - The red swamp crayfish Procambarus clarkii represents an important aquaculture species responsible for over half of all commercial aquaculture profits in Louisiana, USA. White spot syndrome virus (WSSV) is highly pathogenic in crustacean species and induces mass mortality in aquaculture operations worldwide. Natural outbreaks of WSSV occur yearly in cultured populations of crayfish in Louisiana. The goal of this study was to better understand the infectivity of WSSV in P. clarkii, by determining the minimum lethal dose necessary to initiate infection and to measure the resulting cumulative mortality following infection with different doses. A real time quantitative PCR (qPCR) method was used to detect WSSV in DNA extracted from gill tissue to ensure P. clarkii study populations were WSSV-free before the start of trials. Viable viral particles were isolated from naturally infected P. clarkii gill tissue and quantified using a novel digital PCR approach. Three infectivity trials were performed, and WSSV inocula were created by serial dilution, generating 5 treatments per trial. Five crayfish (weighing ~25 g) per dilution per trial received viral inoculations. Mortality was monitored daily for the duration of the trial in order to construct a median lethal dose (LD50) curve, and probit regression analysis was used to determine LD50 concentrations of viral particles. Knowledge of the infectivity of WSSV in native crayfish populations is of critical importance to the management of the commercial crayfish aquaculture industry in Louisiana. This is the first study to investigate the infectivity and to determine the LD50 of the Louisiana strain of WSSV in native crayfish. PMID- 27409238 TI - External injuries of Morelet's crocodile Crocodylus moreletii in Campeche, Mexico. AB - Analysis of external injuries in captive and free-ranging Morelet's crocodiles Crocodylus moreletii was performed in the northern wetlands of Campeche, Mexico. From March to September of 2007, a total of 52 free-ranging and 51 captive Morelet's crocodiles were studied. Captive crocodiles presented significantly more injuries. Sixteen free-ranging crocodiles presented some type of lesion, mostly superficial abrasions. Nineteen captive crocodiles presented lesions, mostly incisions from agonistic interactions. Overall, the injuries with highest prevalence were the incisions. The tail was the most frequently injured body region. Injuries were more common in adults than in other size classes. Conversely, the presence of lesions caused by the parasite Paratrichosoma spp. was greater in crocodiles captured in the coastal channels (mangrove habitat). The information presented here is important to understand some of the effects of individual interactions and to foresee and manage the consequences of conservation and management activities of crocodile populations. PMID- 27409239 TI - Ectopic pregnancy with associated gestational choriocarcinoma in a California sea lion (Zalophus californianus). AB - A wild-born, captive-reared, 14 yr old, primiparous female California sea lion Zalophus californianus presented for anorexia of 14 d duration and abdominal distention. Routine complete blood cell count revealed leukocytosis with a neutrophilia, and serum chemistry revealed hypoalbumenemia and hyponatremia. Treatment with broad spectrum antibiotics and non-steroidal anti-inflammatories were started, but the animal continued to decline. Abdominal radiographs revealed a mature mineralized fetal skull and spine in the caudal abdomen and abdominal ultrasound revealed ascites but could not confirm the fetus. The patient was taken to surgery where a full term fetus was found outside of the uterus but within the fetal membranes, representing a secondary ectopic pregnancy. The patient passed away during surgery and was taken to necropsy. Gross necropsy revealed a diffuse peritonitis with yellow deposits over the serosal surfaces of the abdominal organs. The uterus appeared intact grossly and the ovaries appeared abnormal. The mesenteric, renal, and sub-lumbar nodes were enlarged and edematous. Histopathology revealed choriocarcinoma in the right uterine horn with evidence of chronic uterine rupture and protrusion of the placental tissue into the abdomen. The choriocarcinoma had metastasized locally as well as to the liver, spleen and lung. Choriocarcinoma is a highly malignant trophoblastic neoplasm that is rare in domestic animals. This case represents, to the authors' knowledge, the first report of gestational choriocarcinoma causing secondary ectopic pregnancy in a California sea lion and presents questions regarding pregnancy monitoring and management in a population of captive, minimally trained California sea lions. PMID- 27409240 TI - Detection of a new microsporidium Perezia sp. in shrimps Penaeus monodon and P. indicus by histopathology, in situ hybridization and PCR. AB - Samples of microsporidia-infected shrimps exhibiting clinical signs of cotton shrimp disease were collected from Madagascar, Mozambique, and the Kingdom of Saudi Arabia from 2005 to 2014. The tails of the infected shrimps appeared opaque and whitish; subsequent histological examination revealed the presence of cytoplasmic inclusions and mature spores in tissues of the muscle, hepatopancreas, gills, heart, and lymphoid organ. PCR analysis targeting the small subunit rDNA (SSU rDNA) from infected samples resulted in the amplification of a 1.2 kbp SSU rDNA sequence fragment 94% identical to the corresponding region in the genome of the microsporidian Perezia nelsoni, which infects populations of Penaeus setiferus in the USA. Its SSU rDNA sequence was 100% identical among isolates from Madagascar and Saudi Arabia, indicating that shrimps from the Red Sea and Indian Ocean were infected with the same microsporidium, the novel Perezia sp. A 443 bp fragment of the SSU rDNA sequence was cloned, labeled with digoxigenin and subjected to an in situ hybridization assay with tissue sections of Perezia sp.-infected Penaeus monodon from Madagascar and Mozambique, and P. indicus from Saudi Arabia. The probe hybridized to the mature spores in the hepatopancreas and muscle from which the spores had been obtained for DNA isolation. This assay was specific, showing no reaction to another microsporidium, Enterocytozoon hepatopenaei (EHP), infecting the hepatopancreas of shrimp P. stylirostris cultured in SE Asian countries. We also developed an SSU rDNA-based PCR assay, specific for the novel Perezia sp. This PCR did not react to EHP, nor to genomic DNA of shrimp and other invertebrates. PMID- 27409241 TI - Isolation and genetic characterization of Nocardia seriolae from snubnose pompano Trachinotus blochii in Vietnam. AB - A total of 480 cage-cultured fish were collected from 4 coastal provinces in central Vietnam to investigate the causative agent of nocardiosis. Fish displayed unique characteristics such as paleness and lethargy and exhibited haemorrhages and ulcers on the skin. Prominent white nodules varying in size were observed in the spleen, kidney, and liver. Furthermore, histopathological sections showed typical granulomatous lesions in these organs. Using the Ziehl-Neelsen staining method, isolated bacteria exhibited acid-fast, bead-like filament morphology when cultured in brain-heart infusion medium or Ogawa medium. Phylogenetic analysis of 16S rDNA confirmed that the isolated bacterium was Nocardia seriolae. This study demonstrates for the first time an outbreak of N. seriolae in snubnose pompano in central Vietnam. PMID- 27409242 TI - Peculiar Aqueous Solubility Trend in Cucurbiturils Unraveled by Atomistic Simulations. AB - Cucurbiturils (CBs) compose a family of macrocycles whose elementary unit is glycouril (GLYC). CBs are of high interest in chemistry and biology due to their versatile applications, ranging from sensors to advanced drug-delivery systems. Here, we report a systematic hydration study of all currently known CBs by classical molecular dynamics simulations to understand their different aqueous solubilities, as revealed in the experiments. Water readily penetrates CBs, including the smallest CB, that is, CB[5]. The number of CB[n]-water hydrogen bonds can be assessed as 2 * n. The hydration enthalpies of the CBs were found to be significantly favorable, due to a number of strong hydrogen bonds with water. However, these enthalpy gains are not enough to compensate for an even larger entropic penalty due to modifying a genuine bulk arrangement of water molecules. We found that the free energy of hydration moderately but uniformly increases with the number of GLYCs. Therefore, the better solubility of odd-numbered CBs is independent of the CB-water interactions, either an enthalpic or entropic contribution. The higher solubilities of CB[n]s with n = 5, 7, or 9 occur exclusively because of their amorphous solid states. Our results allow the prognosis of the aqueous solubilities of not-yet-synthesized CBs. PMID- 27409244 TI - A Water-Stable Metal-Organic Framework with a Double-Helical Structure for Fluorescent Sensing. AB - Water instability is a crucial limiting factor in the practical application of most fluorescent metal-organic frameworks (MOFs). Here, by introducing a fascinating double-helical structure generated through dense stacking of organic ligands, a water-stable fluorescence MOF has been synthesized, namely, [Cd2(tib)2(bda)2].(solvent)n (1) [tib =1,3,5-tris(1-imidazolyl) benzene; H2bda = 2,2'-biphenyl dicarboxylic acid]. This helical structure helps to enhance the stability of 1 against common organic solvents and water, even acid/base aqueous solutions with a pH value ranging from 3 to 11. Furthermore, this material can be a potential fluorescent sensor for ketones. PMID- 27409243 TI - A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation. AB - Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal distribution of cAMP at the subcellular level could be important for developing new strategies for the prevention or treatment of unfavorable responses associated with different disease states. PMID- 27409245 TI - Electroformation of Giant Unilamellar Vesicles: Investigating Vesicle Fusion versus Bulge Merging. AB - Partially ordered stacks of phospholipid bilayers on a flat substrate can be obtained by the evaporation of a spread droplet of phospholipid-in-chloroform solution. When exposed to an aqueous buffer, numerous micrometric buds populate the bilayers, grow in size over minutes, and eventually detach, forming the so called liposomes or vesicles. While observation of vesicle growth from a hydrated lipid film under an optical microscope suggests numerous events of vesicle fusion, there is little experimental evidence for discriminating between merging of connected buds, i.e., a shape transformation that does not imply bilayer fusion and real membrane fusion. Here, we use electroformation to grow giant unilamellar vesicles (GUVs) from a stack of lipids in a buffer containing either (i) nanometric liposomes or (ii) previously prepared GUVs. By combining different fluorescent labels of the lipids in the substrate and in the solution, and by performing a fluorescence analysis of the resulting GUVs, we clearly demonstrate that merging of bulges is the essential pathway for vesicle growth in electroformation. PMID- 27409246 TI - Design, Synthesis, and Initial Evaluation of Affinity-Based Small-Molecule Probes for Fluorescent Visualization and Specific Detection of Keap1. AB - Keap1 is a pluripotent protein which plays a predominant role in cellular homeostasis and stress responses. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of Keap1 depends on tools for specific and real-time detection of Keap1. Herein, we report the development of functional affinity-based small-molecule probes which can overcome some shortcomings of current methods and be applied in further studying the function of Keap1. PMID- 27409247 TI - Stereospecific Preparations of P-Stereogenic Phosphonothioates and Phosphonoselenoates. AB - P-Stereogenic phosphonothioates and phosphonoselenoates were readily prepared utilizing RP-menthyl phenylphosphite 1 by two methods. The first method used elemental sulfur or selenium to react with 1, followed by alkylation of the intermediates with alkyl halides. The second used 1 to react with disulfide or diselenide. Both methods stereospecifically produced the title compounds in nearly quantitative yields under mild conditions. Stereospecific chalcogenation of the phosphoryl was proposed as the key step in these reactions. PMID- 27409248 TI - Normal and Frictional Interactions between Liposome-Bearing Biomacromolecular Bilayers. AB - Highly efficient lubricating boundary layers at biosurfaces such as cartilage have been proposed to comprise phospholipids complexed with biomacromolecules exposed at the surfaces. To gain insight into this, a systematic study on the normal and frictional forces between surfaces bearing a sequentially deposited model alginate-on-chitosan bilayer, bearing different adsorbed phosphatidylcholine (PC) liposomes, was carried out using a surface force balance. Structures of the resulting surface complexes were determined using atomic force microscopy (AFM) and cryo-scanning electron microscopy (cryo-SEM). The liposome/lipid-polymer complexes could maintain their integrity up to high pressures in terms of both normal and shear interactions between the surfaces, which were repeatable, reproducible, and revealed very low friction (coefficient of friction MU down to 10(-3)-10(-4), depending on the PC used) up to pressures of hundreds of atm. We attribute this remarkable lubrication capability ultimately to hydration lubrication acting at the hydrated phosphocholine headgroups of the PC lipids, either exposed at the liposome surfaces or through complexation with the polyelectrolyte bilayer. Values of MU, while low, were roughly an order of magnitude higher than for the same PC vesicles adsorbed on bare mica, a difference attributed to their lower density on the bilayer; the bilayer, however, stabilized the PC-vesicles far better than bare mica against rupture and shear at high compressions and sliding. PMID- 27409249 TI - From Peptide Aptamers to Inhibitors of FUR, Bacterial Transcriptional Regulator of Iron Homeostasis and Virulence. AB - FUR (Ferric Uptake Regulator) protein is a global transcriptional regulator that senses iron status and controls the expression of genes involved in iron homeostasis, virulence, and oxidative stress. Ubiquitous in Gram-negative bacteria and absent in eukaryotes, FUR is an attractive antivirulence target since the inactivation of the fur gene in various pathogens attenuates their virulence. The characterization of 13-aa-long anti-FUR linear peptides derived from the variable part of the anti-FUR peptide aptamers, that were previously shown to decrease pathogenic E. coli strain virulence in a fly infection model, is described herein. Modeling, docking, and experimental approaches in vitro (activity and interaction assays, mutations) and in cells (yeast two-hybrid assays) were combined to characterize the interactions of the peptides with FUR, and to understand their mechanism of inhibition. As a result, reliable structure models of two peptide-FUR complexes are given. Inhibition sites are mapped in the groove between the two FUR subunits where DNA should also bind. Another peptide behaves differently and interferes with the dimerization itself. These results define these novel small peptide inhibitors as lead compounds for inhibition of the FUR transcription factor. PMID- 27409250 TI - Influence of Stream Bottom Substrate on Retention and Transport of Vertebrate Environmental DNA. AB - While environmental DNA (eDNA) is now being regularly used to detect rare and elusive species, detection in lotic environments comes with a caveat: The species being detected is likely some distance upstream from the point of sampling. Here, we conduct a series of seminatural stream experiments to test the sensitivity of new digital droplet PCR (ddPCR) to detect low concentrations of eDNA in a lotic system, measure the residence time of eDNA compared to a conservative tracer, and we model the transport of eDNA in this system. We found that while ddPCR improves our sensitivity of detection, the residence time and transport of eDNA does not follow the same dynamics as the conservative tracer and necessitates a more stochastic framework for modeling eDNA transport. There was no evidence for differences in the transport of eDNA due to substrate type. The relatively large amount of unexplained variability in eDNA transport reveals the need for uncovering mechanisms and processes by which eDNA is transported downstream leading to species detections, particularly when inferences are to be made in natural systems where eDNA is being used for conservation management. PMID- 27409251 TI - The circadecadal rhythm of oscillation of umbilical cord blood parameters correlates with geomagnetic activity - An analysis of long-term measurements (1999-2011). AB - Recently, we have shown that the contents of total nucleated cells (TNCs) and CD34+ hematopoietic stem and progenitor cells (CD34+ HSPCs) as well as the cord blood volume (CBV) in umbilical cord blood (UCB) show a circadecadal (~10 years) rhythm of oscillation. This observation was based on an analysis of 17,936 cord blood donations collected during 1999-2011. The aim of the present study was to investigate whether this circadecadal rhythm of oscillation in TNCs, CD34+ HSPCs and CBV is related to geomagnetic activity. For the analysis, the yearly averages of TNCs, CD34+ HSPCs and CBV in UCB were correlated with geomagnetic activity (Dcx index). Our analysis revealed that (i) all three UCB parameters were statistically significantly correlated with the level of geomagnetic activity, (ii) CBV showed a linear correlation with the Dcx index (r = 0.5290), (iii) the number of TNCs and CD34+ HSPCs were quadratic inversely correlated with the Dcx index (r = -0.5343 and r = -0.7749, respectively). Furthermore, (iv) CBV and the number of TNCs were not statistically significantly correlated with the number of either modest or intense geomagnetic storms per year, but (v) the number of CD34+ HSPCs was statistically significantly correlated with the number of modest (r = 0.9253) as well as intense (r = 0.8683) geomagnetic storms per year. In conclusion, our study suggests that UCB parameters correlate with the state of the geomagnetic field (GMF) modulated by solar activity. Possible biophysical mechanisms underlying this observation, as well as the outcome of these findings, are discussed. PMID- 27409252 TI - Spotlight on the three main hepatic fibrogenic cells in HCV-infected patients: Multiple immunofluorescence and ultrastructure study. AB - The present work deals with the simultaneous ultrastructure and triple immunofluorescence study of the three main hepatic fibrogenic cells, hepatic stellate cell, myofibroblast (MF), and fibroblast, in a group of hepatitis C virus (HCV) RNA positive patients, as their exact interrelation behavior in vivo with the progress of hepatic fibrosis is still inadequate. In this study, for the first time, cells having the morphological characteristic of MF and not bone marrow fibrocytes were revealed in liver portal vessels. This necessitates the reevaluation of the available knowledge concerning bone marrow fibrocyte. Also, the distribution, cellular interrelations, and the fate of MF were highlighted. PMID- 27409254 TI - a need to know. PMID- 27409255 TI - Letters. PMID- 27409256 TI - Editor's notes. PMID- 27409253 TI - Objective Assessment of Adherence to Inhalers by Patients with Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported. OBJECTIVES: To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA). METHODS: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCA device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use. MEASUREMENTS AND MAIN RESULTS: Patients with COPD (n = 244) were recruited. The mean age was 71 years, mean FEV1 was 1.3 L, and 59% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses, and critical technique errors, thus incorporating both intentional and unintentional nonadherence, a measure "actual adherence" was calculated. Mean actual adherence was 22.6% of that expected if the doses were taken correctly and on time. Six percent had an actual adherence greater than 80%. Hierarchical clustering found three equally sized well-separated clusters corresponding to distinct patterns. Cluster 1 (34%) had low inhaler use and high error rates. Cluster 2 (25%) had high inhaler use and high error rates. Cluster 3 (36%) had overall good adherence. Poor lung function and comorbidities were predictive of poor technique, whereas age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique. CONCLUSIONS: These data may inform clinicians in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD. PMID- 27409257 TI - Brief Reports. PMID- 27409259 TI - names and faces. PMID- 27409258 TI - coming in sportsmedicine. PMID- 27409260 TI - scanning sports. PMID- 27409262 TI - running wild. PMID- 27409264 TI - Editorial. PMID- 27409265 TI - Exercise and Cystic Fibrosis. AB - In brief: Cystic fibrosis (CF) patients are likely to be less fit than their normal peers, but most can exercise safely. Recent studies show that exercise programs can increase fitness and exercise tolerance. They can also increase the endurance of the respiratory muscles, although pulmonary function will not change. Exercise may be as beneficial as traditional chest physical therapy and postural drainage for getting mucus up from the lungs, but the authors recommend that patients continue therapy until this is confirmed. Because CF patients lose significantly more salt in their sweat than normal people, the authors recommend ample water intake and free access to the salt shaker. PMID- 27409266 TI - Headache in Athletes. AB - In brief: Headache is a common problem in sports medicine, and headache in athletes may differ in some aspects from headache in nonathletes. This article presents an overview of headache and several case histories of headache problems that might be seen by primary care sports physicians. Most athletes' headaches may be secondary to migraine or muscle tension, or they may be cluster headaches. Sometimes no structural cause can be found. Thorough workups are needed to find the causes whenever possible. The physician should keep in mind the athlete's special concerns, such as staying as active as possible. PMID- 27409267 TI - Treatment of Acromioclavicular Sprains in Athletes. AB - In brief: The most common mechanism of acromioclavicular joint trauma is injury by direct force that occurs when the patient falls onto the point of the shoulder, usually with the arm at the side in adduction. Mild and moderate sprains are treated conservatively with ice and range-of-motion exercises. In addition, moderate sprains are immobilized. Physicians must choose "nontreatment," conservative treatment, or surgery for severe sprains after considering the concomitant injuries, general surgical risks, cosmetic results, length of treatment, extremity involved, and the patient's age. Specific surgical procedures vary according to age, type of ligament tear, and the condition of the distal clavicle. PMID- 27409268 TI - Equestrian Injuries. AB - In brief: It has always been assumed that participants in equestrian sports are at high risk of serious injury and that minor injuries are common. This study of American Horse Shows Association and United States Pony Clubs horse shows tried to determine if shows are as safe as or safer than other sports, what the accident rate is for horse shows, if any factors influence the accident rate, and what types of accidents and injuries occur. There were 290 reported injuries and two deaths in the 984 responding shows. The accident rate per entry was 0.0003. There was no statistically significant relationship between any external factors and the accident rate. Anecdotes usually indicate a preponderance of shoulder injuries, but the statistics did not find this to be so. Bruises and being "shook up" accounted for 45.5% of the injuries, and fractures 15.5%. PMID- 27409269 TI - Wrestling Injuries in North Carolina High Schools. AB - In brief: Using data on 1,091 North Carolina high school wrestlers during 49 team seasons, the authors attempted to relate the number, type, and severity of wrestling injuries to factors such as mat surfaces, endurance exercises, weight- reducing methods, protective equipment, and coaching experience. Most of the 248 injuries were minor, causing little time loss, but 57 (23%) were so severe that athletes missed an entire season. Possible contributory factors were inappropriate endurance training shoes, infrequent headgear use during practice, less than optimum wrestler-to-coach ratios, and potentially dangerous weight reduction methods. PMID- 27409270 TI - Neurological Injuries in Winter Sports. AB - In brief: Eighty-two of the 126 patients with neurological injuries caused by winter sports sustained concussion. Twenty-nine of these concussions were caused by collisions while skiing. Injuries also were related to inner tubes, snow disks, sleds, toboggans, a ski bob, a snowmobile, and a Sno-Cat. Six accidents were related to chair lifts. The author believes that for every 100 patients who have skiing injuries requiring orthopedic treatment, five to ten sustain injuries to the neurological system. The worst injuries in this study involved hitting trees, other skiers, boulders, or ski lift equipment or performing aerial maneuvers. PMID- 27409271 TI - AAFDBI: Bringing Fitness to Corporate America. AB - AAFDBI has been successful In selling the virtues of employee fitness programs, but their contribution to the bottom line Is hard to prove. PMID- 27409272 TI - Are Employee Fitness Programs for Everyone? PMID- 27409273 TI - Meeting notes. PMID- 27409275 TI - Sportsmedicine adviser. PMID- 27409277 TI - Pharmaceutical patent law: expert perspectives from around the globe. PMID- 27409278 TI - Acceptance of internet-based hearing healthcare among adults who fail a hearing screening. AB - OBJECTIVE: This study measured help-seeking readiness and acceptance of existing internet-based hearing healthcare (IHHC) websites among a group of older adults who failed a hearing screening (Phase 1). It also explored the effects of brief training on participants' acceptance of IHHC (Phase 2). STUDY SAMPLE: Twenty seven adults (age 55+) who failed a hearing screening participated. DESIGN: During Phase 1 participants were administered the University of Rhode Island Change Assessment (URICA) and patient technology acceptance model (PTAM) Questionnaire. During Phase 2 participants were randomly assigned to a training or control group. Training group participants attended an instructional class on existing IHHC websites. The control group received no training. The PTAM questionnaire was re-administered to both groups 4-6 weeks following the initial assessment. RESULTS: The majority of participants were either considering or preparing to do something about their hearing loss, and were generally accepting of IHHC websites (Phase 1). The participants who underwent brief IHHC training reported increases in hearing healthcare knowledge and slight improvements in computer self-efficacy (Phase 2). CONCLUSIONS: Older adults who fail hearing screenings may be good candidates for IHHC. The incorporation of a simple user interface and short-term training may optimize the usability of future IHHC programs for this population. PMID- 27409279 TI - The effect of individual differences in working memory in older adults on performance with different degrees of automated technology. AB - A leading hypothesis to explain older adults' overdependence on automation is age related declines in working memory. However, it has not been empirically examined. The purpose of the current experiment was to examine how working memory affected performance with different degrees of automation in older adults. In contrast to the well-supported idea that higher degrees of automation, when the automation is correct, benefits performance but higher degrees of automation, when the automation fails, increasingly harms performance, older adults benefited from higher degrees of automation when the automation was correct but were not differentially harmed by automation failures. Surprisingly, working memory did not interact with degree of automation but did interact with automation correctness or failure. When automation was correct, older adults with higher working memory ability had better performance than those with lower abilities. But when automation was incorrect, all older adults, regardless of working memory ability, performed poorly. Practitioner Summary: The design of automation intended for older adults should focus on ways of making the correctness of the automation apparent to the older user and suggest ways of helping them recover when it is malfunctioning. PMID- 27409280 TI - Coming in postgraduate medicine. PMID- 27409281 TI - Problems solutions. PMID- 27409282 TI - What's happening in medicine. PMID- 27409283 TI - Washington background. PMID- 27409285 TI - ReadySource on Headache. PMID- 27409284 TI - Self-test. PMID- 27409286 TI - Clinical Outlines. PMID- 27409287 TI - Pamphlets for Patients. PMID- 27409289 TI - Therapeutic Index to Advertisers. PMID- 27409290 TI - Native rhizobia from Zn mining soil promote the growth of Leucaena leucocephala on contaminated soil. AB - Plants on contaminated mining soils often show a reduced growth due to nutrient depletion as well as trace elements (TEs) toxicity. Since those conditions threat plant's survival, plant growth-promoting rhizobacteria (PGPRs), such as rhizobia, might be of crucial importance for plant colonization on TE-contaminated soils. Native rhizobia from mining soils are promising candidates for bioaugmented phytoremediation of those soils as they are adapted to the specific conditions. In this work, rhizobia from Zn- and Cd-contaminated mining soils were in vitro screened for their PGP features [organic acids, indole-3-acetic acid (IAA), and siderophore (SID) production; 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity; and Ca3(PO4)2 solubilization] and Zn and Cd tolerance. In addition, some type and reference rhizobia strains were included in the study as well. The in vitro screening indicated that rhizobia and other native genera have great potential for phytoremediation purposes, by exerting, besides biological N2 fixation, other plant growth-promoting traits. Leucaena leucocephala Mesorhizobium sp. (UFLA 01-765) showed multielement tolerance and an efficient symbiosis on contaminated soil, decreasing the activities of antioxidative enzymes in shoots. This symbiosis is a promising combination for phytostabilization. PMID- 27409291 TI - Commentary on "New Perspectives on Drug Education/Prevention". PMID- 27409292 TI - Dr. Rosenbaum Responds. PMID- 27409294 TI - On-demand ultrasonography assessment in the most symptomatic joint supports the 8 joint score system for management of rheumatoid arthritis patients. AB - OBJECTIVES: To investigate whether on-demand ultrasonography (US) assessment alongside a routine examination is useful in the management of rheumatoid arthritis (RA). METHODS: US was performed in eight (bilateral MCP 2, 3, wrist and knee) joints as the routine in a cumulative total of 406 RA patients. The most symptomatic joint other than the routine joints was additionally scanned. Power Doppler (PD) and gray-scale images were scored semiquantitatively. Eight-joint scores were calculated as the sum of individual scores for the routine joints. RESULTS: The most symptomatic joint was found among the routine joints in 209 patients (Group A) and in other joints in 148 (Group B). The PD scores of the most symptomatic joint correlated well with the 8-joint scores in Group A (rs = 0.66), but not in Group B (rs = 0.33). The sensitivity and specificity of assessment of the most symptomatic joint for routine assessment positivity were high (84.0% and 100%, respectively) in Group A, but low (50.0% and 61.8%, respectively) in Group B. Additional examination detected synovitis in 38% of Group B with negative results in the routine. CONCLUSIONS: On-demand US assessment in the most symptomatic joint, combined with the routine assessment, is useful for detecting RA synovitis. PMID- 27409295 TI - MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure. AB - INTRODUCTION: Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways. PMID- 27409296 TI - In Memoriam Robert Ponlot (1923-2008): L'esprit du coeur dans une main de bienfaisance. PMID- 27409297 TI - Combined approach of isotope mass balance and hydrological water balance methods to constrain the sources of lake water as exemplified on the small dimictic lake Silbersee, northern Germany. AB - Stable isotopes of hydrogen and oxygen are often used for water balance calculations of lakes. We present an approach combining the lake water balance with an isotope mass balance to constrain the sources and sinks of the water of a small dimictic lake subjected to eutrophication. Meteorological and hydraulic data in combination with measured isotope signatures of the different water compartments enabled to assess the degree of surface water/groundwater interaction and the amount of overland flow into the lake. Groundwater could be excluded as a lake water source, as its water level was always below the lake water level. In the absence of a channelled inflow, precipitation and overland flow were the remaining options, whereby the latter was only active during periods of exceptionally high rainfall. While the groundwater signatures adjacent to the lake showed an influence of lake water, the lake water balance itself indicated that the associated volumetric water loss to groundwater is rather negligible. In the present case, only a combined assessment of hydrological and isotopic data allowed for an accurate characterization of the studied lake and a quantification of its water sources and sinks, highlighting the importance of using more than one methodological approach for such a purpose. PMID- 27409298 TI - Descriptive Statistics of the Genome: Phylogenetic Classification of Viruses. AB - The typical process for classifying and submitting a newly sequenced virus to the NCBI database involves two steps. First, a BLAST search is performed to determine likely family candidates. That is followed by checking the candidate families with the pairwise sequence alignment tool for similar species. The submitter's judgment is then used to determine the most likely species classification. The aim of this article is to show that this process can be automated into a fast, accurate, one-step process using the proposed alignment-free method and properly implemented machine learning techniques. We present a new family of alignment free vectorizations of the genome, the generalized vector, that maintains the speed of existing alignment-free methods while outperforming all available methods. This new alignment-free vectorization uses the frequency of genomic words (k-mers), as is done in the composition vector, and incorporates descriptive statistics of those k-mers' positional information, as inspired by the natural vector. We analyze five different characterizations of genome similarity using k-nearest neighbor classification and evaluate these on two collections of viruses totaling over 10,000 viruses. We show that our proposed method performs better than, or as well as, other methods at every level of the phylogenetic hierarchy. The data and R code is available upon request. PMID- 27409293 TI - Immunization of HIV-infected adult patients - French recommendations. AB - Human immunodeficiency virus (HIV)-infected patients remain at increased risk of infection including vaccine-preventable diseases. Vaccines are therefore critical components in the protection of HIV-infected patients from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV infected patients persist and vaccine coverage in this population could be improved. This article presents the French recommendations regarding immunization of HIV-infected adults in the light of the evidence-based literature on the benefits and the potential risks of vaccines among this vulnerable population. PMID- 27409299 TI - Glutamate-Based Drug Discovery for Novel Antidepressants. AB - INTRODUCTION: Classic antidepressants that modulate monoaminergic systems are not sufficiently effective and require long systematic application. Recent studies suggest that substances that modulate glutamatergic system may produce an antidepressant effect which is not only faster but also more sustained. AREAS COVERED: In this paper, the authors summarize the results of studies on antidepressant action of ketamine in patients with severe refractory depression, which have demonstrated high efficacy in a very short time after a single dose. Due to the adverse effects of ketamine that substantially exclude it from the daily use by patients, efforts have been made to find other NMDA receptor antagonists, which could mimic the therapeutic effect of ketamine but without the side effects. Intensive studies to elucidate ketamine's mechanism of antidepressant action have also been conducted. Herein, the results of research showing that metabotropic glutamate (mGlu) receptors could be the target of novel antidepressants are also presented. EXPERT OPINION: The intensive preclinical and clinical research on NMDA and mGlu receptor ligands, which is currently going on, could contribute to the awaited breakthrough in the field of novel antidepressant drug discovery. This line of research may also lead to a new understanding of the biological basis of depression. PMID- 27409301 TI - Binary-tree encryption strategy for optical multiple-image encryption. AB - In traditional optical multiple-image encryption schemes, different images typically have almost the same encryption or decryption process. Provided that an attacker manages to correctly decrypt some image, the conventional attacks upon other images are much easier to be made. In this paper, a binary-tree encryption strategy for multiple images is proposed to resist the attacks in this case. The encryption schemes produced by this strategy can not only increase the security of multiple-image encryption, but also realize an authority management with high security among the users sharing a cipher image. For a simulation test, we devise a basic binary-tree encryption scheme, whose encryption nodes are based on an asymmetric double random phase encoding in the gyrator domain. The favorable simulation results about the tested scheme can testify to the feasibility of the strategy. PMID- 27409302 TI - Active and passive imaging of clothes in the NIR and SWIR regions for reflectivity analysis. AB - We perform statistical analysis of data from active and passive imaging sensors in the near infrared (NIR) and short wavelength infrared (SWIR) wavelength bands. The data were obtained from measurements performed on clothing in a field campaign and in the laboratory. We show that reflectivity data from active imaging can be fitted to Gaussian functions, although earlier theory proposes gamma-gamma functions. We analyze the reflectivity data collected during the field campaign and compare that data with data obtained in the laboratory. We focus on the added value of active imaging when combined with passive imaging to distinguish different clothes for friend/foe identification. PMID- 27409300 TI - Associations of Poor Housing with Mental Health Among North Carolina Latino Migrant Farmworkers. AB - This analysis examines the associations of housing conditions with mental health among migrant farmworkers. Data are from a 2010 cross-sectional study conducted in 16 North Carolina counties. Interviews and housing inspections were completed with 371 farmworkers in 186 camps. Mental health measures included depression (Center for Epidemiologic Studies Depression Scale, CES-D), anxiety (Personality Assessment Inventory, PAI), and alcohol misuse (Alcohol Use Disorders Identification Test, AUDIT-C). Housing measures were number of people per sleeping room, perceived security of self and belongings, having a key to dwelling's door, having bedroom storage, toilet privacy issues, and number of housing regulation violations. Sixty (16.7%) participants had substantial depressive symptoms (CES-D >=10), 31 (8.8%) had substantial anxiety (PAI >=27), and 185 (50.1%) had the potential for alcohol misuse (AUDIT-C >=4). Those with 5+ persons sleeping per room were more likely to have a depression score >=10 (31.5% vs. 13-14%, P = .01) and an anxiety scores >=27 (19.6% vs. 5-9%, P = .02). Those who did not feel they or their belongings were secure were more likely to have a depression score >=10 (19.4% vs. 9.1%, P = .01). Those without a key were more likely to have an anxiety score >=27 (11.5% vs. 5.1%, P = .04). Those with no bedroom storage were more likely to have a depression score >=10 (28.9% vs. 14.9%, P = .03). This article suggests links between poor housing and farmworkers' mental health. These results inform regulations surrounding farmworker housing and inform health care providers on how to prevent and treat poor mental health among migrant farmworkers. PMID- 27409303 TI - Large aperture focus stacking with max-gradient flow by anchored rolling filtering. AB - Focus stacking is a computational technique to extend the depth of field through combining multiple images taken at various focus distances. However, in the large aperture case, there are always defects caused by the large blur scale, which, to the best of our knowledge, has not been well studied. In our work, we propose a max-gradient flow-based method to reduce artifacts and obtain a high-quality all in-focus image by anchored rolling filtering. First, we define a max-gradient flow to describe the gradient propagation in the stack. The points are divided into trivial and source points with this flow. The source points are extracted as true edge points and are utilized as anchors to refine the depth map and the composited all-in-focus image iteratively. The experiments show that our method can effectively suppress the incorrect depth estimations and give a high-quality all-in-focus image. PMID- 27409304 TI - Comparison of 2D and 3D flame topography measured by planar laser-induced fluorescence and tomographic chemiluminescence. AB - The goal of this work was to contrast and compare the 2D and 3D flame topography of a turbulent flame. The 2D measurements were obtained using CH-based (methylidyne radical-based) planar laser-induced fluorescence (PLIF), and the 3D measurements were obtained through a tomographic chemiluminescence (TC) technique. Both PLIF and TC were performed simultaneously on a turbulent premixed Bunsen flame. The PLIF measurements were then compared to a cross section of the 3D TC measurements, both to provide a validation to the 3D measurements and also to illustrate the differences in flame structures inferred from the 2D and 3D measurements. PMID- 27409305 TI - Fingerprint detection and mapping using a phase shifted coherent gradient sensing technique. AB - In this paper, a full field technique for mapping a latent fingerprint using a coherent gradient sensing (CGS) sensor is proposed. Collimated light from an He Ne laser illuminates a specimen comprising a fingerprint implanted onto a reflecting surface. Reflected light from the specimen is analyzed using the CGS sensor comprising a pair of gratings. Reflected light carries information regarding the depth and orientation of furrows and ridges in the fingerprint. The topological information of the fingerprint is retrieved using four-step phase shifting interferometry. Well-defined 2D and 3D phase plots have been reconstructed to map the topography of the human fingerprint. The recorded slope data reconstructs the information regarding the separation and depth of the ridges in the latent fingerprint. The proposed technique is noninvasive and full field and does not require any kind of chemical or physical treatment. The sensor is very simple, yields interferometric sensitivity, and has the advantages of easy alignment, compactness, and low cost. PMID- 27409306 TI - Fourier transform spectrometer based on Fabry-Perot interferometer. AB - We analyze the Fourier transform spectrometer based on a symmetric/asymmetric Fabry-Perot interferometer. In this spectrometer, the interferogram is obtained by recording the intensity as a function of the interferometer length. Then, we recover the spectrum by applying the discrete Fourier transform (DFT) directly on the interferogram. This technique results in spectral harmonic overlap and fictitious wavenumber components outside the original spectral range. For this purpose, in this work, we propose a second method to recover the spectrum. This method is based on expanding the DFT of the interferogram and the spectrum by a Haar or box function. By this second method, we recovered the spectrum and got rid of the fictitious spectral components and spectral harmonic overlap. PMID- 27409307 TI - Quadrature wavelength scanning interferometry. AB - A novel method to double the measurement range of wavelength scanning interferometery (WSI) is described. In WSI the measured optical path difference (OPD) is affected by a sign ambiguity, that is, from an interference signal it is not possible to distinguish whether the OPD is positive or negative. The sign ambiguity can be resolved by measuring an interference signal in quadrature. A method to obtain a quadrature interference signal for WSI is described, and a theoretical analysis of the advantages is reported. Simulations of the advantages of the technique and of signal errors due to nonideal quadrature are discussed. The analysis and simulation are supported by experimental measurements to show the improved performances. PMID- 27409308 TI - High power single-frequency Innoslab amplifier. AB - A laser diode array (LDA) end-pumped continuous-wave single-frequency Innoslab amplifier has been demonstrated. The Gaussian ray bundle method was used to model the light propagation in the Innoslab amplifier for the first time to the best of our knowledge. With discrete reflectors, the maximum output of 60 W with a linewidth of 44 MHz was achieved under the pump power of 245 W, corresponding to the optical-optical efficiency of 24.5%. The beam quality factor M2 at the output power of 51 W in the horizontal and vertical direction was measured to be 1.4 and 1.3, respectively. The long-term power instability in 2 h was less than 0.25%. PMID- 27409309 TI - Angle-invariant imaging using a total internal reflection virtual aperture. AB - Conventional lens stops, implemented with an absorptive physical aperture, have an angle-dependent projection that introduces field dependent loss and reduces diffraction-limited resolution. Retro-telephoto lenses obtain uniform response using aberration vignetting, but this results in low wide-angle resolution and significant lens volume. However, an angle-independent "virtual" aperture can be created by total internal reflection (TIR) from a thin low index layer inside the lens. We apply this to monocentric wide-angle imaging and find a simple relationship between the filtering layer index and radius and the resulting lens F/#. We provide two detailed designs of lenses with 12 mm focal length and a F/2.5 TIR stop, one using a low index adhesive within a solid fixed-focus lens, the other using an air cavity within an adjustable focus lens. We show the designs provide absolutely uniform resolution and light collection over an angle range of 84 degrees and 106 degrees , respectively, resulting in a dramatic improvement of both light collection and angular resolution per unit volume over conventional wide-angle lenses. PMID- 27409310 TI - Optimization of Ta2O5 optical thin film deposited by radio frequency magnetron sputtering. AB - Radio frequency magnetron sputtering has been used here to find the parameters at which to deposit Ta2O5 optical thin films with negligible absorption in the visible spectrum. The design of experiment methodology was employed to minimize the number of experiments needed to find the optimal results. Two independent approaches were used to determine the index of refraction n and k values. PMID- 27409311 TI - Determination of nonlinear nanomechanical resonator-qubit coupling coefficient in a hybrid quantum system. AB - We have theoretically investigated a hybrid system that is composed of a traditional optomechanical component and an additional charge qubit (Cooper pair box) that induces a new nonlinear interaction. It is shown that the peak in optomechanically induced transparency has been split by the new nonlinear interaction, and the width of the splitting is proportional to the coupling coefficient of this nonlinear interaction. This may give a way to measure the nanomechanical oscillator-qubit coupling coefficient in hybrid quantum systems. PMID- 27409312 TI - Practical system for generating digital mixed reality video holograms. AB - We propose a practical system that can effectively mix the depth data of real and virtual objects by using a Z buffer and can quickly generate digital mixed reality video holograms by using multiple graphic processing units (GPUs). In an experiment, we verify that real objects and virtual objects can be merged naturally in free viewing angles, and the occlusion problem is well handled. Furthermore, we demonstrate that the proposed system can generate mixed reality video holograms at 7.6 frames per second. Finally, the system performance is objectively verified by users' subjective evaluations. PMID- 27409313 TI - Verification and improvement of equivalent refractive index models for evaluating the shielding effectiveness of high-transmittance double-layer metallic meshes. AB - The validity of real and complex equivalent refractive index models (ERIMs) is verified for a shielding effectiveness evaluation of high-transmittance double layer metallic meshes. Theoretical and experimental studies show that the real ERIM is invalid for thin substrates and inaccurate for thick substrates for double-layer meshes, although it has long been used successfully for single-layer meshes. However, the complex ERIM shows more reasonable results not only for double-layer but also for single-layer meshes, and the evaluation accuracy is further improved by modifying the equivalent reactance coefficient using least squares fitting. Therefore, the modified complex ERIM is applicable in most conditions. PMID- 27409314 TI - Analytical solution for first-order scattering in bistatic radiative transfer interaction problems of layered media. AB - An approximate solution to the radiative transfer equation for bistatic scattering from a rough surface covered by a tenuous distribution of particulate (scattering and absorbing) media is derived by means of a series expansion in the scattering coefficient kappas of the covering layer up to the first order. The formulation of the successive orders of a scattering series is reviewed, and an analytic solution to the first-order interaction contribution is given by means of a series expansion of the azimuthally averaged product of the bidirectional reflectance distribution function of the surface and the scattering phase function of the covering layer. PMID- 27409315 TI - Fluorescence plasmonic enhancement of FITC labeled PS nanoparticles coupled to silver island films. AB - Optical properties of a fluorescence molecule can be drastically changed by surface plasmons excited in neighboring metallic nanostructures. Here we investigated the fluorescence enhancement behavior of fluorescein isothiocyanate (FITC) labeled polystyrene nanoparticles coupled to silver island films (SIFs) via a 15 nm polymethyl methacrylate separation layer theoretically and experimentally. Up to 24-fold fluorescence enhancement was experimentally achieved when the annealing time of the 25 nm Ag films was 50 min, which is in good agreement with the theoretical simulation result based on the finite difference time-domain method. Furthermore, significant fluorescence spectral distortion on SIFs was also observed compared with samples on glass slides, which is sufficiently related to the scattering properties of SIFs and the lifetimes of FITC. PMID- 27409316 TI - Directional random laser source consisting of a HC-ARROW reservoir connected to channels for spectroscopic analysis in microfluidic devices. AB - Light sources are used in optofluidic devices for real-time system control and quantitative analysis of important process parameters. In this work, we present a random laser source using a hollow-core antiresonant reflecting optical waveguide (HC-ARROW) containing the gain media inside a reservoir to reduce dye bleaching, which is connected to microchannel waveguides to increase beam directionality. The device is pumped externally and emits a highly coherent and collimated laser beam. PMID- 27409317 TI - Optimization of multi-grating volume holographic spectrum splitters for photovoltaic applications. AB - Recent research has shown that using multiple diverse-bandgap photovoltaic (PV) cells in conjunction with a spectrum splitting optical system can significantly improve PV power generation efficiency. Although volume Bragg gratings (VBGs) can serve as effective spectrum splitters, the inherent dispersion of a VBG can be detrimental given a broad-spectrum input. The performance of a single holographic spectrum splitter element can be improved by utilizing multiple single volume gratings, each operating in a slightly different spectral band. However, care must be taken to avoid inter-grating coupling effects that limit the ultimate performance. This work explores broadband two-grating holographic optical elements (HOEs) in multiplexed (single element) and sandwiched-grating arrangements. Particle swarm optimization is used to tailor these systems to the solar spectrum, taking into account both efficiency and dispersion. Both multiplexed and sandwiched two-grating systems exhibit performance improvements over single-grating solutions, especially when reduced dispersion is required. Under a +/-2 degrees constraint on output angular spread from wavelength dispersion, sandwiched-, multiplexed-, and single-grating systems exhibit power conversion efficiencies of 82.1%, 80.9%, and 77.5%, respectively, compared to an ideal bandpass spectrum splitter. Dispersion performance can be further improved by employing more than two VBGs in the spectrum splitter, but efficiency is compromised by additional cross-coupling effects. Multiplexed-grating systems are especially susceptible to these effects, but have the advantage of utilizing only a single HOE. PMID- 27409318 TI - Photoreduced silver nanoparticles grown on femtosecond laser ablated, D-shaped fiber probe for surface-enhanced Raman scattering. AB - Surface-enhanced Raman scattering (SERS) probes are made by facile photochemical deposition of silver nanoparticles on a femtosecond (fs) laser ablated, D-shaped fiber. The structure and surface morphology of the probe are investigated by scanning electron microscopy. High-quality SERS signals are detected using Rhodamine 6G molecules via an in situ sensing mode. Experimental results show that the SERS signals increase with the increase of the length of fs laser ablated, D-shaped zone. Our D-shaped fiber SERS probe shows a feasible method for a large active area, high performance, and real-time and remote measurement of SERS signals in biochemical analysis. PMID- 27409319 TI - Shack-Hartmann wavefront sensor with large dynamic range by adaptive spot search method. AB - A Shack-Hartmann wavefront sensor (SHWFS) that consists of a microlens array and an image sensor has been used to measure the wavefront aberrations of human eyes. However, a conventional SHWFS has finite dynamic range depending on the diameter of the each microlens. The dynamic range cannot be easily expanded without a decrease of the spatial resolution. In this study, an adaptive spot search method to expand the dynamic range of an SHWFS is proposed. In the proposed method, spots are searched with the help of their approximate displacements measured with low spatial resolution and large dynamic range. By the proposed method, a wavefront can be correctly measured even if the spot is beyond the detection area. The adaptive spot search method is realized by using the special microlens array that generates both spots and discriminable patterns. The proposed method enables expanding the dynamic range of an SHWFS with a single shot and short processing time. The performance of the proposed method is compared with that of a conventional SHWFS by optical experiments. Furthermore, the dynamic range of the proposed method is quantitatively evaluated by numerical simulations. PMID- 27409320 TI - Gain-switched Ti:sapphire laser-based photoacoustic imaging. AB - We demonstrate photoacoustic (PA) imaging using a compact gain-switched Ti:sapphire laser. Additionally, a simple laser configuration is provided. The Ti:sapphire laser is pumped using a frequency-doubled pulsed neodymium-doped yttrium aluminum garnet pulse laser operating at a repetition rate of 10 Hz, with a pump energy of 37 mJ. No water cooling is required for the Ti:sapphire crystal. The output pulse energy and pulse duration of the laser are 13.6 mJ and 11 ns, respectively. Thus, the power conversion efficiency is 36.7%. As the end mirror in a laser cavity is adjusted in a horizontal direction, the output wavelength can be tuned within a range of 725-880 nm with a spectral bandwidth of approximately 1 nm. The laser has a small footprint size of 50 cm*35 cm including even laser pumping. Because the near-infrared region has significant advantages in the context of absorption and scattering in biological tissues, our laser can be used for PA imaging. Apart from obtaining PA images of a tube filled with indocyanine green immersed in water and placed under chicken breast tissue, our laser system could also be used for the simultaneous PA and ultrasound (US) dual modality imaging of blood vessels lying beneath the skin of a human middle finger. We used a commercially available US machine for the PA and US dual modality imaging. PMID- 27409321 TI - Investigation of ellipsometric parameters of 2D microrough surfaces by FDTD. AB - Ellipsometry is a powerful method for measuring the optical constants of materials and is very sensitive to surface roughness. In previous ellipsometric measurement of optical constants of solid materials with rough surfaces, researchers frequently used effective medium approximation (EMA) with roughness already known to fit the complex refractive index of the material. However, the ignored correlation length, the other important parameter of rough surfaces, will definitely result in fitting errors. Hence it is necessary to consider the influence of surface roughness and correlation length on the ellipsometric parameters Delta (phase difference) and Psi (azimuth) characterizing practical systems. In this paper, the influence of roughness of two-dimensional randomly microrough surfaces (relative roughness sigma/lambda ranges from 0.001 to 0.025) of silicon on ellipsometric parameters was simulated by the finite-difference time-domain method which was validated with experimental results. The effects of incident angle, relative roughness, and correlation length were numerically investigated for two-dimensional Gaussian distributed randomly microrough surfaces, respectively. The simulated results showed that compared with the smooth surface, only tiny changes of the ellipsometric parameter Delta could be observed for microrough silicon surface in the vicinity of the Brewster angle, but obviously changes of Psi occur especially in the vicinity of the Brewster angle. More differences between the ellipsometric parameters of the rough surface and smooth surface can been seen especially in the vicinity of the Brewster angle as the relative roughness sigma/lambda increases or correlation length tau decreases. The results reveal that when we measure the optical constants of solid materials by ellipsometry, the smaller roughness, larger correlation length and larger incident wavelength will lead to the higher precision of measurements. PMID- 27409322 TI - Image restoration method for longitudinal laser tomography based on degradation matrix estimation. AB - Target images captured by longitudinal laser tomography are usually degraded by nonuniform laser beams transmitting through inhomogeneous scattering mediums. An image restoration method with a total variation model is proposed for eliminating the main influence of inhomogeneous scattering mediums from degraded target images. Based on the physical signal relevance between the target layer and the scattering medium layer, the degradation matrix of the target image is approximately estimated by the specified backscattering images of the scattering mediums. Simulations and experiments are performed to verify the validity and feasibility of the proposed method, and all the results demonstrate that the proposed model works well and helps us to achieve the real target images, which represent the reflectivity distributions of the targets standing behind the inhomogeneous scattering mediums and which will benefit target recognition and identification. PMID- 27409323 TI - Phase tuning in two-dimensional coherently coupled vertical-cavity surface emitting laser array. AB - Implant-defined vertical-cavity surface-emitting laser (VCSEL) arrays can be designed to operate in in-phase mode. However, the nonuniformities in fabrication process impact the resonance selection and the devices do not follow expected trends. Coherent coupling was demonstrated in three-element VCSEL arrays via phase tuning of elements. In-phase mode and out-of-phase mode were both achieved in most of the arrays. Moreover, coherent coupling can decrease the threshold current of elements in the array. Improved output power was also clearly observed when the array operated in the in-phase mode. Arbitrary phase combination of the array elements can be obtained via the phase tuning. This technology is able to improve the reproducibility and practicability of the implant-defined coherently coupled VCSEL array. PMID- 27409324 TI - 759 fs pulse generation with Nd3+-doped CNGS ordered crystal based on a semiconductor saturable absorber mirror. AB - A diode-pumped passively continuous wave mode-locked laser at 1064.2 nm based on an ordered Nd:CNGS crystal has been experimentally investigated (for the first time, to our knowledge). Stable mode-locked pulses with a duration of 759 fs were produced at a repetition rate of 43.2 MHz. It is the shortest pulse generation of mode-locked lasers based on Nd3+-doped ordered crystal, as far as we know. A maximum average mode-locked output power of 133 mW was obtained at the absorbed pumped power of 6.7 W, and corresponding single-pulse energy and peak power were determined to be 3.1 nJ and 4.1 kW, respectively. The results indicate that the Nd:CNGS as an ordered crystal is indeed a potential candidate as a femtosecond laser gain medium. PMID- 27409325 TI - On optimal filtering of measured Mueller matrices. AB - While any 2D mixed state of polarization of light can be represented by a combination of a pure state and a fully random state, any Mueller matrix can be represented by a convex combination of a pure component and three additional components whose randomness is scaled in a proper and objective way. Such characteristic decomposition constitutes the appropriate framework for the characterization of the polarimetric randomness of the system represented by a given Mueller matrix and provides criteria for the optimal filtering of noise in experimental polarimetry. PMID- 27409326 TI - Simple method for determination of parameters of cemented doublet. AB - This paper proposes a simple noninvasive method that makes it possible to calculate the inner design parameters of the cemented doublet using measurements of its chosen paraxial optical and geometrical parameters without any damage to the system under testing (e.g., dismantling). Derived formulas are based on the knowledge of measured values of the lenses thicknesses, the radii of curvatures of the first and the last doublet's surfaces, the paraxial focal length, and positions of the object and the image focal point. Practical usefulness of the proposed method is demonstrated on the real measurement of a known doublet. PMID- 27409327 TI - Hybrid approach for fast occlusion processing in computer-generated hologram calculation. AB - A hybrid approach for fast occlusion processing in computer-generated hologram calculation is studied in this paper. The proposed method is based on the combination of two commonly used approaches that complement one another: the point-source and wave-field approaches. By using these two approaches together, the proposed method thus takes advantage of both of them. In this method, the 3D scene is first sliced into several depth layers parallel to the hologram plane. Light scattered by the scene is then propagated and shielded from one layer to another using either a point-source or a wave-field approach according to a threshold criterion on the number of points within the layer. Finally, the hologram is obtained by computing the propagation of light from the nearest layer to the hologram plane. Experimental results reveal that the proposed method does not produce any visible artifact and outperforms both the point-source and wave field approaches. PMID- 27409328 TI - CR-100 synthetic zeolite adsorption characteristics toward Northern Banat groundwater ammonia. AB - The adsorption characteristics of synthetic zeolite CR-100 in a fixed-bed system using continuous flow of groundwater containing elevated ammonia concentration were examined. The possibilities for adsorbent mass calculation throughout mass transfer zone using novel mathematical approach as well as zeolite adsorption capacity at every sampling point in time or effluent volume were determined. The investigated adsorption process consisted of three clearly separated steps indicated to sorption kinetics. The first step was characterized by decrease and small changes in effluent ammonia concentration vs. experiment time and quantity of adsorbed ammonia per mass unit of zeolite. The consequences of this phenomenon were showed in the plots of the Freundlich and the Langmuir isotherm models through a better linear correlation according as graphical points contingent to the first step were not accounted. The Temkin and the Dubinin-Radushkevich isotherm models showed the opposite tendency with better fitting for overall measurements. According to the obtained isotherms parameter data, the investigated process was found to be multilayer physicochemical adsorption, and also that synthetic zeolite CR-100 is a promising material for removal of ammonia from Northern Banat groundwater with an ammonia removal efficiency of 90%. PMID- 27409329 TI - Reduced Oral Bioavailability and Altered Pharmacokinetics of Saquinavir by Co administration with Biochanin A in Rats. AB - The study was aim to assess the impact of biochanin A on the oral bioavailability and pharmacokinetics (PK) of saquinavir (SQV), a substrate of P-glycoprotein (P gp), in rats. 10 male rats were randomized into 2 groups of equal size, and administered orally 30 mg/kg SQV with or without 20 mg/kg biochanin A. The PK of SQV was assessed using non-compartmental analysis. Results revealed that the area under the plasma concentration-time curve of SQV from time zero to time infinity (AUC0-infinity) was reduced by 51.39% by biochanin A (P=0.038); while the apparent systemic clearance (CL/F) was increased by 87.62% (P=0.028). Double peak phenomenon was observed in the plasma SQV profiles. Biochanin A increased the first peak, yet decreased the second peak of plasma SQV levels. Our study demonstrates that biochanin A can significantly reduce SQV oral bioavailability and alter SQV PK profiles in rats. Findings in this study suggest a precaution in the clinic when SQV is administered with dietary/herbal supplements that contain biochanin A. PMID- 27409330 TI - Designing and in Silico Analysis of PorB Protein from Chlamydia Trachomatis for Developing a Vaccine Candidate. AB - Bakground: Chlamydia trachomatis is an obligate, intracellular, gram-negative bacterium that causes sexually transmitted infections. The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is a target for neutralizing antibodies (Abs); thus, making it important for vaccine development. Methods: We used an in silico strategy and homology modeling algorithms and focused on PorB of C. trachomatis and explained its characterization with the help of bioinformatic tools to introduce it as a candidate for novel drug and vaccine design. In this study, physicochemical characterization, secondary and 3D structure, and functional site prediction were investigated. Then, a B cell epitope was analyzed using Immune Epitope Database, which predicts the target region and helps in vaccine development. Results: PorB is a surface-exposed protein comprising 340 amino acids and frequently appears (61.76%) as a random coiled structure. PorB was present outside the cell and the maximum length of the predicted epitope was from amino acids 91-108, i. e., 18 amino acids long. This epitope can be considered for designing Abs and vaccines against C. trachomatis. Conclusion: Although many attempts have been made to develop a vaccine against C. trachomatis, no protective vaccines are available to date. More detailed studies focusing on PorB should be performed to design vaccines against C. trachomatis because of the presence of different immunization protocols and requirement of different protective mechanisms. PMID- 27409331 TI - Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia. AB - We evaluated the impact of postprandial glycemia on blood levels of pro inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon alpha (IFN-alpha), interferon-gamma (IFN-gamma), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-gamma inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-gamma (MIG), macrophage inflammatory protein-1alpha (MIP-1alpha), interleukin-1beta (IL-1beta), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor alpha (TNFalpha), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1alpha (MIP 1alpha), and 1beta (MIP-1beta) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL 17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL 5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia was associated with increased blood levels of anti inflammatory and pro-inflammatory cytokines. PMID- 27409332 TI - Enhancement of anti-OVA IgG2c production in vivo by enalapril. AB - Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA) specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8 week-old C57BL/6 females mice (3-4/group) were subcutaneously immunized with OVA (10 MUg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at -20 degrees C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production. PMID- 27409334 TI - Obesity inversely correlates with prostate-specific antigen levels in a population with normal screening results of prostate cancer in northwestern China. AB - Serum prostate-specific antigen (PSA) is a diagnostic biomarker of prostate cancer and is possibly associated with obesity. This study aimed to explore the relationships between obesity indicators [body mass index (BMI) and waist circumference (WC)] with PSA in Chinese men. A cross-sectional study of men aged 30-85 years undergoing prostate cancer screening was conducted from August 2008 to July 2013 in Xi'an, China. Data were obtained from clinical reports, condition was recorded based on self-report including demographics, weight, height, and WC (>90 cm=obese). Fasting blood glucose (FBG) and prostate volume (PV) were assessed clinically. Patients were grouped by BMI (normal=22.9, overweight=23 27.4, obese>=27.5 kg/m2). PSA parameters of density (PSAD), PSA serum level, and PSA increasing rate per year (PSAR) were calculated per BMI and age groups (30 40, 41-59, 60-85 years). Obesity indicators (BMI and WC) and PSA parameter relationships were modeled by age-stratified linear regression. Of 35,632 Chinese men surveyed, 13,084 were analyzed, including 13.44% obese, 57.44% overweight, and 29.12% normal weight, according to BMI; 25.84% were centrally (abdominally) obese according to WC. BMI and WC were negatively associated with all PSA parameters, except PSAD and PSAR [P<0.05, BMI: beta=-0.081 (95%CI=-0.055 to 0.036), WC: beta=-0.101 (-0.021 to -0.015)], and independent of FBG and PV (P<0.05) in an age-adjusted model. In conclusion, obesity was associated with lower PSA in Chinese men. Therefore, an individual's BMI and WC should be considered when PSA is used to screen for prostate cancer. PMID- 27409333 TI - Does the incremental shuttle walk test require maximal effort in young obese women? AB - Obesity is a chronic disease with a multifaceted treatment approach that includes nutritional counseling, structured exercise training, and increased daily physical activity. Increased body mass elicits higher cardiovascular, ventilatory and metabolic demands to varying degrees during exercise. With functional capacity assessment, this variability can be evaluated so individualized guidance for exercise training and daily physical activity can be provided. The aim of the present study was to compare cardiovascular, ventilatory and metabolic responses obtained during a symptom-limited cardiopulmonary exercise test (CPX) on a treadmill to responses obtained by the incremental shuttle walk test (ISWT) in obese women and to propose a peak oxygen consumption (VO2) prediction equation through variables obtained during the ISWT. Forty obese women (BMI >=30 kg/m2) performed one treadmill CPX and two ISWTs. Heart rate (HR), arterial blood pressure (ABP) and perceived exertion by the Borg scale were measured at rest, during each stage of the exercise protocol, and throughout the recovery period. The predicted maximal heart rate (HRmax) was calculated (210 - age in years) (16) and compared to the HR response during the CPX. Peak VO2 obtained during CPX correlated significantly (P<0.05) with ISWT peak VO2 (r=0.79) as well as ISWT distance (r=0.65). The predictive model for CPX peak VO2, using age and ISWT distance explained 67% of the variability. The current study indicates the ISWT may be used to predict aerobic capacity in obese women when CPX is not a viable option. PMID- 27409335 TI - Sida tuberculata (Malvaceae): a study based on development of extractive system and in silico and in vitro properties. AB - Sida tuberculata (Malvaceae) is a medicinal plant traditionally used in Brazil as an antimicrobial and anti-inflammatory agent. Here, we aimed to investigate the different extractive techniques on phytochemical parameters, as well as to evaluate the toxicity and antioxidant capacity of S. tuberculata extracts using in silico and in vitro models. Therefore, in order to determine the dry residue content and the main compound 20-hydroxyecdysone (20E) concentration, extracts from leaves and roots were prepared testing ethanol and water in different proportions. Extracts were then assessed by Artemia salina lethality test, and toxicity prediction of 20E was estimated. Antioxidant activity was performed by DPPH and ABTS radical scavenger assays, ferric reducing power assay, nitrogen derivative scavenger, deoxyribose degradation, and TBARS assays. HPLC evaluation detected 20E as main compound in leaves and roots. Percolation method showed the highest concentrations of 20E (0.134 and 0.096 mg/mL of extract for leaves and roots, respectively). All crude extracts presented low toxic potential on A. salina (LD50 >1000 ug/mL). The computational evaluation of 20E showed a low toxicity prediction. For in vitro antioxidant tests, hydroethanolic extracts of leaves were most effective compared to roots. In addition, hydroethanolic extracts presented a higher IC50 antioxidant than aqueous extracts. TBARS formation was prevented by leaves hydroethanolic extract from 0.015 and 0.03 mg/mL and for roots from 0.03 and 0.3 mg/mL on egg yolk and rat tissue, respectively (P<0.05). These findings suggest that S. tuberculata extracts are a considerable source of ecdysteroids and possesses a significant antioxidant property with low toxic potential. PMID- 27409336 TI - Effects of fluoride on proliferation and mineralization in periodontal ligament cells in vitro. AB - Fluoride, which is often added to toothpaste or mouthwash in order to protect teeth from decay, may be a novel therapeutic approach for acceleration of periodontal regeneration. Therefore, we investigated the effects of fluoride on proliferation and mineralization in human periodontal ligament cells in vitro. The periodontal ligament cells were stimulated with various concentrations of NaF added into osteogenic inductive medium. Immunohistochemistry of cell identification, cell proliferation, alkaline phosphatase (ALP) activity assay, Alizarin red S staining and quantitative real-time-polymerase chain reaction (RT PCR) were performed. Moderate concentrations of NaF (50-500 MUmol/L) had pro proliferation effects, while 500 MUmol/L had the best effects. ALP activity and calcium content were significantly enhanced by 10 MUmol/L NaF with osteogenic inductive medium. Quantitative RT-PCR data varied in genes as a result of different NaF concentrations and treatment periods. We conclude that moderate concentrations of NaF can stimulate proliferation and mineralization in periodontal ligament cells. These in vitro findings may provide a novel therapeutic approach for acceleration of periodontal regeneration by addition of suitable concentrations of NaF into the medication for periodontitis treatment, i.e., into periodontal packs and tissue patches. PMID- 27409337 TI - Sentinel node biopsy using blue dye and technetium99 in advanced gastric cancer: anatomical drainage and clinical application. AB - Lymph node metastases are an independent prognosis factor in gastric carcinoma (GC) patients. Radical lymphadenectomy can improve survival but it can also increase surgical morbidity. As a principle, sentinel node (SN) navigation surgery can avoid unnecessary lymphadenectomy without compromising prognosis. In this pilot study, 24 patients with untreated GC were initially screened for SN navigation surgery, of which 12 were eligible. Five patients had T2 tumors, 5 had T3 tumors and 2 had T1 tumors. In 33% of cases, tumor diameter was greater than 5.0 cm. Three hundred and eighty-seven lymph nodes were excised with a median of 32.3 per patient. The SN navigation surgery was feasible in all patients, with a median of 4.5 SNs per patient. The detection success rate was 100%. All the SNs were located in N1 and N2 nodal level. In 70.9% of cases, the SNs were located at lymphatic chains 6 and 7. The SN sensitivity for nodal staging was 91.6%, with 8.3% of false negative. In 4 patients who were initially staged as N0, the SNs were submitted to multisection analyses and immunohistochemistry, confirming the N0 stage, without micrometastases. In one case initially staged as negative for nodal metastases based on SN analyses, metastases in lymph nodes other than SN were found, resulting in a 20% skip metastases incidence. This surgery is a reproducible procedure with 100% detection rate of SN. Tumor size, GC location and obesity were factors that imposed some limitations regarding SN identification. Results from nodal multisection histology and immunohistochemistry analysis did not change initial nodal staging. PMID- 27409338 TI - Rituximab in children with steroid-dependent nephrotic syndrome: experience of a tertiary center and review of the literature. AB - OBJECTIVES: Rituximab (RTX) is a new treatment option in children with difficult to-treat steroid-dependent nephrotic syndrome (SDNS). We evaluated the experience of our tertiary center and reviewed the current literature. METHODS: This is a retrospective single-center study evaluating the efficacy and safety of RTX in children with difficult-to-treat SDNS. Age at diagnosis, type and duration of immunosuppression, age at administration, dose of RTX, possible adverse events, number of relapses, duration of remission, and B-cell count after administration of RTX were analyzed. RESULTS: Nine children with a median age at diagnosis of nephrotic syndrome of 4.75 (range 1.33-11.33) years and a median age at administration of RTX of 16.08 (range 3.33-19.25) years were included. Before administration of RTX they had a median number of relapses per year of 1.70 (range 0.82-4.80). At last follow-up (median 2.75 years, range 0.58-3.92), a reduction in the number of relapses per year to 0.26 (range 0-2.18) was noted, despite cessation or lowering the dose of immunosuppressive therapy. Four patients achieved complete remission after the first administration of RTX, four more patients after subsequent doses of RTX. No severe adverse events were noted. CONCLUSION: RTX was an effective and safe therapeutic option in our cohort of children with difficult-to-treat SDNS, resulting in a significant reduction of yearly relapses in the absence of severe adverse events and facilitating the reduction of other immunosuppressive medication. PMID- 27409339 TI - Nonlinear tumor evolution from dysplastic nodules to hepatocellular carcinoma. AB - Dysplastic nodules are premalignant neoplastic nodules found in explanted livers with cirrhosis. Genetic signatures of premalignant dysplastic nodules (DNs) with concurrent hepatocellular carcinoma (HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis. We analyzed four patients with multifocal nodular lesions and cirrhotic background by whole-exome sequencing (WES). The genomic profiles of somatic single nucleotide variations (SNV) and copy number variations (CNV) in DNs were compared to those of HCCs. The number and variant allele frequency of somatic SNVs of DNs and HCCs in each patient was identical along the progression of pathological grade. The somatic SNVs in DNs showed little conservation in HCC. Additionally, CNVs showed no conservation. Phylogenetic analysis based on SNVs and copy number profiles indicated a nonlinear segregation pattern, implying independent development of DNs and HCC in each patient. Thus, somatic mutations in DNs may be developed separately from other malignant nodules in the same liver, suggesting a nonlinear model for hepatocarcinogenesis from DNs to HCC. PMID- 27409341 TI - Synthetic ligands of death receptor 5 display a cell-selective agonistic effect at different oligomerization levels. AB - DR4 (Death Receptor 4) and DR5 (Death Receptor 5) are two potential targets for cancer therapy due to their ability to trigger apoptosis of cancer cells, but not normal ones, when activated by their cognate ligand TRAIL (TNF related apoptosis inducing ligand). Therapies based on soluble recombinant TRAIL or agonist antibodies directed against one of the receptors are currently under clinical trials. However, TRAIL-R positive tumor cells are frequently resistant to TRAIL induced apoptosis. The precise mechanisms of this resistance are still not entirely understood. We have previously reported on synthetic peptides that bind to DR5 (TRAILmim/DR5) and induce tumor cell apoptosis in vitro and in vivo. Here, we showed that while hexameric soluble TRAIL is able to efficiently kill the DR5 positive lymphoma Jurkat or the carcinoma HCT116, these cells are resistant to apoptosis induced by the divalent form of TRAILmim/DR5 and are poorly sensitive to apoptosis induced by an anti-DR5 agonist monoclonal antibody. This resistance can be restored by the cross-linking of anti-DR5 agonist antibody but not by the cross-linking of the divalent form of TRAILmim/DR5. Interestingly, the divalent form of TRAILmim/DR5 that induced apoptosis of DR5 positive BJAB cells, acts as an inhibitor of TRAIL-induced apoptosis on Jurkat and HCT116 cells. The rapid internalization of DR5 observed when treated with divalent form of TRAILmim/DR5 could explain the antagonist activity of the ligand on Jurkat and HCT116 cells but also highlights the independence of the mechanisms responsible for internalization and activation when triggering the DR5 apoptotic cascade. PMID- 27409342 TI - Meta-dimensional data integration identifies critical pathways for susceptibility, tumorigenesis and progression of endometrial cancer. AB - Endometrial Cancer (EC) is one of the most common female cancers. Genome-wide association studies (GWAS) have been investigated to identify genetic polymorphisms that are predictive of EC risks. Here we utilized a meta dimensional integrative approach to seek genetically susceptible pathways that may be associated with tumorigenesis and progression of EC. We analyzed GWAS data obtained from Connecticut Endometrial Cancer Study (CECS) and identified the top 20 EC susceptible pathways. To further verify the significance of top 20 EC susceptible pathways, we conducted pathway-level multi-omics analyses using EC exome-Seq, RNA-Seq and survival data, all based on The Cancer Genome Atlas (TCGA) samples. We measured the overall consistent rankings of these pathways in all four data types. Some well-studied pathways, such as p53 signaling and cell cycle pathways, show consistently high rankings across different analyses. Additionally, other cell signaling pathways (e.g. IGF-1/mTOR, rac-1 and IL-5 pathway), genetic information processing pathway (e.g. homologous recombination) and metabolism pathway (e.g. sphingolipid metabolism) are also highly associated with EC risks, diagnosis and prognosis. In conclusion, the meta-dimensional integration of EC cohorts has suggested some common pathways that may be associated from predisposition, tumorigenesis to progression. PMID- 27409343 TI - Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas. AB - The forkhead box M1 (FOXM1) transcription factor gene has been implicated in almost all human cancer types. It would be an ideal biomarker for cancer detection but, to date, its translation into a cancer diagnostic tool is yet to materialise. The quantitative Malignancy Index Diagnostic System (qMIDS) was the first FOXM1 oncogene-based diagnostic test developed for quantifying squamous cell carcinoma aggressiveness. The test was originally validated using head and neck squamous cell carcinomas (HNSCC) from European patients. The HNSCC gene expression signature across geographical and ethnic differences is unknown. This is the first study evaluated the FOXM1-based qMIDS test using HNSCC specimens donated by ethnic Chinese patients. We tested 50 Chinese HNSCC patients and 18 healthy subjects donated 68 tissues in total. qMIDS scores from the Chinese cohort were compared with the European datasets (n = 228). The median +/- SD scores for the Chinese cohort were 1.13 +/- 0.66, 4.02 +/- 1.66 and 5.83 +/- 3.13 in healthy oral tissues, adjacent tumour margin and HNSCC core tissue, respectively. Diagnostic test efficiency between the Chinese and European datasets was almost identical. Consistent with previous European data, qMIDS scores for HNSCC samples were not influenced by gender or age. The degree of HNSCC differentiation, clinical stage and lymphatic metastasis status were found to be correlated with qMIDS scores. This study provided the first evidence that the pathophysiology of HNSCC was molecularly indistinguishable between the Chinese and European specimens. The qMIDS test robustly quantifies a universal FOXM1-driven oncogenic program, at least in HNSCC, which transcends ethnicity, age, gender and geographic origins. PMID- 27409344 TI - Systemic immune-inflammation index predicts the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib. AB - BACKGROUND: In this retrospective analysis, we explored the prognostic and predictive value of the systemic immune-inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, at baseline and changes at week 6 during first-line sunitinib in patients with metastatic renal cell cancer (RCC). RESULTS: Patients were stratified into high SII (>= 730) and low SII (< 730) groups. SII was associated with objective response, p < 0.0001. The median PFS was 6.3 months (95% CI 5.5-8.9) in patients with SII >= 730 and 18.7 months (95% CI 14.7-22.8) in those with SII < 730, p < 0.0001. The median OS was 43.6 months (95% CI 35.3-52.1) in patients with SII < 730, and 13.5 months (95% CI 9.8-18.5) in those with SII >= 730, p < 0.0001. In multivariate analysis, performance status, IMDC score and SII were able to predict OS (HR = 3.29, HR = 1.71 and HR = 1.79, respectively). MATERIALS AND METHODS: We included 335 consecutive RCC patients treated with first-line sunitinib. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan Meier method and compared with logrank test. The impact of SII conversion at week 6 of treatment on PFS and OS was evaluated by Cox regression analyses. CONCLUSIONS: The SII and its changes during treatment represent a powerful prognostic indicator of clinical outcome in patients with metastatic RCC. PMID- 27409345 TI - Loss of MYC and E-box3 binding contributes to defective MYC-mediated transcriptional suppression of human MC-let-7a-1~let-7d in glioblastoma. AB - Previously, we reported that MYC oncoprotein down-regulates the transcription of human MC-let-7a-1~let-7d microRNA cluster in hepatocarcinoma (HCC). Surprisingly, in silico analysis indicated that let-7 miRNA expression levels are not reduced in glioblastoma (GBM). Here we investigated the molecular basis of this differential expression. Using human GBM U87 and U251 cells, we first demonstrated that forced over-expression of MYC indeed could not down-regulate the expression of human MC-let-7a-1~let-7d microRNA cluster in GBM. Furthermore, analysis of MC-let-7a-1~let-7d promoter in GBM indicated that MYC failed to inhibit the promoter activity. Pearson's correlation and Linear Regression analysis using the expression data from GSE55092 (HCC) and GSE4290 (GBM) demonstrated a converse relationship of MC-let-7a-1~let-7d and MYC only in HCC but not in GBM. To understand the underlying mechanisms, we examined whether MYC could bind to the non-canonical E-box 3 located in the promoter of MC-let-7a 1~let-7d. Results from both chromatin immune-precipitation (ChIP) and super-shift assays clearly demonstrated the loss of MYC and E-box 3 binding in GBM, suggesting for the first time that a defective MYC and E-box3 binding in GBM is responsible for the differential MYC mediated transcriptional inhibition of MC let-7a-1~let-7d and potentially other tumor suppressors. MYC and let-7 are key oncoprotein and tumor suppressor, respectively. Understanding the molecular mechanisms of their regulations will provide new insight and have important implications in the therapeutics of GBM as well as other cancers. PMID- 27409346 TI - Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma. AB - Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient derived cell lines. We have analyzed three metastases from a patient with high grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis. Genomic aberrations of several potentially targetable genes, including amplification of KITLG and FRS2, in addition to amplification of CDK4 and MDM2, characteristic of this disease, were identified. We evaluated the efficacy of drugs targeting these aberrations or the corresponding signaling pathways in a cell line derived from the patient. Interestingly, the pan-FGFR inhibitor NVP-BGJ398, which targets FGFR upstream of FRS2, strongly inhibited cell proliferation in vitro and induced an accumulation of cells into the G0 phase of the cell cycle. This study indicates that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2. PMID- 27409349 TI - Leveraging the Information from Markov State Models To Improve the Convergence of Umbrella Sampling Simulations. AB - Umbrella sampling (US) simulation is a highly effective method for sampling the conformations of a complex system within a small subspace of predefined coordinates. In a typical US stratification strategy, biasing "window" potentials spanning the subspace of interest are introduced to narrow down the range of accessible conformations and accelerate the sampling. The speed of convergence in each biased window simulation may, however, differ. For example, windows that coincide with a large energetic barrier along a coordinate that is orthogonal to the predefined subspace are often plagued by slow relaxation timescales. Here, we design a method that can quantitatively detect this type of issue and gain further insight into the origin of the slow relaxation timescale. Once the problematic windows affected by slow convergence are identified, additional simulations limited to only these windows can be carried out, thereby reducing the overall computational effort. Several possible approaches aimed at performing US simulations adaptively are discussed, and their respective performance is illustrated using a simple model system. Last, simulations of an atomic deca alanine system are used to demonstrate the efficacy of analyzing US simulation trajectories using the proposed method. PMID- 27409348 TI - Identification and validation of regulatory SNPs that modulate transcription factor chromatin binding and gene expression in prostate cancer. AB - Prostate cancer (PCa) is the second most common solid tumor for cancer related deaths in American men. Genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with the increased risk of PCa. Because most of the susceptibility SNPs are located in noncoding regions, little is known about their functional mechanisms. We hypothesize that functional SNPs reside in cell type-specific regulatory elements that mediate the binding of critical transcription factors (TFs), which in turn result in changes in target gene expression. Using PCa-specific functional genomics data, here we identify 38 regulatory candidate SNPs and their target genes in PCa. Through risk analysis by incorporating gene expression and clinical data, we identify 6 target genes (ZG16B, ANKRD5, RERE, FAM96B, NAALADL2 and GTPBP10) as significant predictors of PCa biochemical recurrence. In addition, 5 SNPs (rs2659051, rs10936845, rs9925556, rs6057110 and rs2742624) are selected for experimental validation using Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay in LNCaP cells, showing allele-specific enhancer activity. Furthermore, we delete the rs2742624-containing region using CRISPR/Cas9 genome editing and observe the drastic downregulation of its target gene UPK3A. Taken together, our results illustrate that this new methodology can be applied to identify regulatory SNPs and their target genes that likely impact PCa risk. We suggest that similar studies can be performed to characterize regulatory variants in other diseases. PMID- 27409347 TI - The down-regulated ING5 expression in lung cancer: a potential target of gene therapy. AB - ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. We found that ING5 overexpression not only inhibited proliferation, migration, and invasion, but also induced G2 arrest, differentiation, autophagy, apoptosis, glycolysis and mitochondrial respiration in lung cancer cells. ING5 transfection up-regulated the expression of Cdc2, ATG13, ATG14, Beclin-1, LC-3B, AIF, cytochrome c, Akt1/2/3, ADFP, PFK-1 and PDPc, while down-regulated the expression of Bcl-2, XIAP, survivin,beta-catenin and HXK1. ING5 transfection desensitized cells to the chemotherapy of MG132, paclitaxel, and SAHA, which paralleled with apoptotic alteration. ING5 overexpression suppressed the xenograft tumor growth by inhibiting proliferation and inducing apoptosis. ING5 expression level was significantly higher in normal tissue than that in lung cancer at both protein and mRNA levels. Nuclear ING5 expression was positively correlated with ki-67 expression and cytoplasmic ING5 expression. Cytoplasmic ING5 expression was positively associated with lymph node metastasis, and negatively with age, lymphatic invasion or CPP32 expression. ING5 expression was different in histological classification: squamous cell carcinoma > adenocarcinoma > large cell carcinoma > small cell carcinoma. Taken together, our data suggested that ING5 downregulation might involved in carcinogenesis, growth, and invasion of lung cancer and could be considered as a promising marker to gauge the aggressiveness of lung cancer. It might be employed as a potential target for gene therapy of lung cancer. PMID- 27409350 TI - Assessment of nanoparticles and metal exposure of airport workers using exhaled breath condensate. AB - Aircraft engine exhaust increases the number concentration of nanoparticles (NP) in the surrounding environment. Health concerns related to NP raise the question of the exposure and health monitoring of airport workers. No biological monitoring study on this profession has been reported to date. The aim was to evaluate the NP and metal exposure of airport workers using exhaled breath condensate (EBC) as a non-invasive biological matrix representative of the respiratory tract. EBC was collected from 458 French airport workers working either on the apron or in the offices. NP exposure was characterized using particle number concentration (PNC) and size distribution. EBC particles were analyzed using dynamic light scattering (DLS) and scanning electron microscopy coupled to x-ray spectroscopy (SEM-EDS). Multi-elemental analysis was performed for aluminum (Al), cadmium (Cd) and chromium (Cr) EBC contents. Apron workers were exposed to higher PNC than administrative workers (p < 0.001). Workers were exposed to very low particle sizes, the apron group being exposed to even smaller NP than the administrative group (p < 0.001). The particulate content of EBC was brought out by DLS and confirmed with SEM-EDS, although no difference was found between the two study groups. Cd concentrations were higher in the apron workers (p < 0.001), but still remained very low and close to the detection limit. Our study reported the particulate and metal content of airport workers airways. EBC is a potential useful tool for the non-invasive monitoring of workers exposed to NP and metals. PMID- 27409351 TI - YCa3(CrO)3(BO3)4: A Cr(3+) Kagome Lattice Compound Showing No Magnetic Order down to 2 K. AB - We report a new gaudefroyite-type compound YCa3(CrO)3(BO3)4, in which Cr(3+) ions (3d(3), S = 3/2) form an undistorted kagome lattice. Using a flux agent, the synthesis was significantly accelerated with the typical calcining time reduced from more than 2 weeks to 2 d. The structure of YCa3(CrO)3(BO3)4 was determined by combined Rietveld refinements against X-ray and neutron diffraction data. Symmetry distortion refinement starting from a disordered YCa3(MnO)3(BO3)4 model was applied to avoid overparameterization. There are two ordering models, namely, K2-1 and K2-2, with the space groups P63 (No. 173) and P3 (No. 147), respectively, that differ in the [BO3] ordering between different channels (in phase or out-of-phase). Both models give similarly good fits to the diffraction data. YCa3(CrO)3(BO3)4 is an insulator with the major band gap at Eg = 1.65 eV and a second transition at 1.78 eV. Magnetically, YCa3(CrO)3(BO3)4 is dominated by anti-ferromagnetic exchange along edge-sharing CrO6 octahedral chains perpendicular to the kagome planes, with Theta ~ -120 K and MUeff ~ 3.92 MUB. The compound shows no spin ordering or freezing down to at least 2 K. PMID- 27409352 TI - Continuous On-Chip Cell Separation Based on Conductivity-Induced Dielectrophoresis with 3D Self-Assembled Ionic Liquid Electrodes. AB - Dielectrophoresis (DEP) has been widely explored to separate cells for various applications. However, existing DEP devices are limited by the high cost associated with the use of noble metal electrodes, the need of high-voltage electric field, and/or discontinuous separation (particularly for devices without metal electrodes). We developed a DEP device with liquid electrodes, which can be used to continuously separate different types of cells or particles based on positive DEP. The device is made of polydimethylsiloxane (PDMS), and ionic liquid is used to form the liquid electrodes, which has the advantages of low cost and easy fabrication. Moreover, the conductivity gradient is utilized to achieve the DEP-based on-chip cell separation. The device was used to separate polystyrene microbeads and PC-3 human prostate cancer cells with 94.7 and 1.2% of the cells and microbeads being deflected, respectively. This device is also capable of separating live and dead PC-3 cancer cells with 89.8 and 13.2% of the live and dead cells being deflected, respectively. Moreover, MDA-MB-231 human breast cancer cells could be separated from human adipose-derived stem cells (ADSCs) using this device with high purity (81.8 and 82.5% for the ADSCs and MDA-MB-231 cells, respectively). Our data suggest the great potential of cell separation based on conductivity-induced DEP using affordable microfluidic devices with easy operation. PMID- 27409353 TI - Heat Transfer through a Condensate Droplet on Hydrophobic and Nanostructured Superhydrophobic Surfaces. AB - Understanding the fundamental mechanisms governing vapor condensation on nonwetting surfaces is crucial to a wide range of energy and water applications. In this paper, we reconcile classical droplet growth modeling barriers by utilizing two-dimensional axisymmetric numerical simulations to study individual droplet heat transfer on nonwetting surfaces (90 degrees < thetaa < 170 degrees ). Incorporation of an appropriate convective boundary condition at the liquid vapor interface reveals that the majority of heat transfer occurs at the three phase contact line, where the local heat flux can be up to 4 orders of magnitude higher than at the droplet top. Droplet distribution theory is incorporated to show that previous modeling approaches underpredict the overall heat transfer by as much as 300% for dropwise and jumping-droplet condensation. To verify our simulation results, we study condensed water droplet growth using optical and environmental scanning electron microscopy on biphilic samples consisting of hydrophobic and nanostructured superhydrophobic regions, showing excellent agreement with the simulations for both constant base area and constant contact angle growth regimes. Our results demonstrate the importance of resolving local heat transfer effects for the fundamental understanding and high fidelity modeling of phase change heat transfer on nonwetting surfaces. PMID- 27409355 TI - Bronsted Acid Catalyzed Homoconjugate Addition of Organotrifluoroborates to Arylated Cyclopropyl Ketones. AB - A novel and practical homoconjugate addition of alkenyl, alkynyl, heteroaryl, and aryl trifluoroborates to arylated cyclopropyl ketones to synthesize gamma,gamma disubstituted ketones is reported. A preliminary mechanistic proposal involving ketone protonation, an intermediary carbocation, and intermolecular nucleophile addition has been made based on control studies. PMID- 27409356 TI - "Grafting to" of RAFTed Responsive Polymers to Glass Substrates by Thiol-Ene and Critical Comparison to Thiol-Gold Coupling. AB - Surface-grafted polymers have been widely applied to modulate biological interfaces and introduce additional functionality. Polymers derived from reversible addition-fragmentation transfer (RAFT) polymerization have a masked thiol at the omega-chain end providing an anchor point for conjugation and in particular displays high affinity for gold surfaces (both flat and particulate). In this work, we report the direct grafting of RAFTed polymers by a "thiol-ene click" (Michael addition) onto glass substrates rather than gold, which provides a more versatile surface for subsequent array-based applications but retains the simplicity. The immobilization of two thermoresponsive polymers are studied here, poly[oligo(ethylene glycol) methyl ether methacrylate] (pOEGMA) and poly(N isopropylacrylamide) (pNIPAM). Using a range of surface analysis techniques the grafting efficiency was compared to thiol-gold and was quantitatively compared to the gold alternative using quartz crystal microbalance. It is shown that this method gives easy access to grafted polymer surfaces with pNIPAM resulting in significantly increased surface coverage compared to pOEGMA. The nonfouling (protein resistance) character of these surfaces is also demonstrated. PMID- 27409357 TI - Identification of Four Kinds of 2',3'-cNMPs in Escherichia coli and a Method for Their Preparation. AB - Four kinds of 2',3'-cNMPs have been identified in animals and plants, and their physiological roles are also suggested. However, in prokaryotes, while 2',3'-cCMP and 2',3'-cUMP are reported, 2',3'-cGMP or 2',3'-cAMP have never been identified from bacteria or archaea. In addition, there has been no biological method to prepare these cyclic nucleotides. During the study of a novel gene LfliZ from deep-sea bacterium Pseudoalteromonas sp. SM9913, we found that the recombinant LfliZ oligomers contained endogenous substrates, which were then identified to be 2',3'-cCMP, 2',3'-cUMP, 2',3'-cGMP, and 2',3'-cAMP, showing the first evidence for the biological existence of four kinds of 2',3'-cNMPs in prokaryotes. In addition, we further developed a biological method to simultaneously prepare four kinds of 2',3'-cNMPs from Escherichia coli through expressing LfliZ. PMID- 27409354 TI - Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds. AB - Peptidyl-proline isomerases (PPIases) are a chaperone superfamily comprising the FK506-binding proteins (FKBPs), cyclophilins, and parvulins. PPIases catalyze the cis/trans isomerization of proline, acting as a regulatory switch during folding, activation, and/or degradation of many proteins. These "clients" include proteins with key roles in cancer, neurodegeneration, and psychiatric disorders, suggesting that PPIase inhibitors could be important therapeutics. However, the active site of PPIases is shallow, solvent-exposed, and well conserved between family members, making selective inhibitor design challenging. Despite these hurdles, macrocyclic natural products, including FK506, rapamycin, and cyclosporin, bind PPIases with nanomolar or better affinity. De novo attempts to derive new classes of inhibitors have been somewhat less successful, often showcasing the "undruggable" features of PPIases. Interestingly, the most potent of these next-generation molecules tend to integrate features of the natural products, including macrocyclization or proline mimicry strategies. Here, we review recent developments and ongoing challenges in the inhibition of PPIases, with a focus on how natural products might inform the creation of potent and selective inhibitors. PMID- 27409358 TI - Investigation of the Switching Mechanism in TiO2-Based RRAM: A Two-Dimensional EDX Approach. AB - The next generation of nonvolatile memory storage may well be based on resistive switching in metal oxides. TiO2 as transition metal oxide has been widely used as active layer for the fabrication of a variety of multistate memory nanostructure devices. However, progress in their technological development has been inhibited by the lack of a thorough understanding of the underlying switching mechanisms. Here, we employed high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) combined with two-dimensional energy dispersive X-ray spectroscopy (2D EDX) to provide a novel, nanoscale view of the mechanisms involved. Our results suggest that the switching mechanism involves redistribution of both Ti and O ions within the active layer combined with an overall loss of oxygen that effectively render conductive filaments. Our study shows evidence of titanium movement in a 10 nm TiO2 thin-film through direct EDX mapping that provides a viable starting point for the improvement of the robustness and lifetime of TiO2-based resistive random access memory (RRAM). PMID- 27409359 TI - The Role of Iron-Bearing Minerals in NO2 to HONO Conversion on Soil Surfaces. AB - Nitrous acid (HONO) accumulates in the nocturnal boundary layer where it is an important source of daytime hydroxyl radicals. Although there is clear evidence for the involvement of heterogeneous reactions of NO2 on surfaces as a source of HONO, mechanisms remain poorly understood. We used coated-wall flow tube measurements of NO2 reactivity on environmentally relevant surfaces (Fe (hydr)oxides, clay minerals, and soil from Arizona and the Saharan Desert) and detailed mineralogical characterization of substrates to show that reduction of NO2 by Fe-bearing minerals in soil can be a more important source of HONO than the putative NO2 hydrolysis mechanism. The magnitude of NO2-to-HONO conversion depends on the amount of Fe(2+) present in substrates and soil surface acidity. Studies examining the dependence of HONO flux on substrate pH revealed that HONO is formed at soil pH < 5 from the reaction between NO2 and Fe(2+)(aq) present in thin films of water coating the surface, whereas in the range of pH 5-8 HONO stems from reaction of NO2 with structural iron or surface complexed Fe(2+) followed by protonation of nitrite via surface Fe-OH2(+) groups. Reduction of NO2 on ubiquitous Fe-bearing minerals in soil may explain HONO accumulation in the nocturnal boundary layer and the enhanced [HONO]/[NO2] ratios observed during dust storms in urban areas. PMID- 27409360 TI - Atomic-Level Characterization of the Chain-Flipping Mechanism in Fatty-Acids Biosynthesis. AB - During fatty acids biosynthesis the elongating acyl chain is sequestered within the core of the highly conserved acyl carrier protein (ACP). At each catalytic step, the acyl intermediates are transiently delivered from ACP to the active site of the enzymatic counterparts and, at the same time, are protected from the solvent to prevent nonselective reactivity. Yet, the molecular determinants of such a universal transition-termed chain flipping-remain poorly understood. Here we capture the atomic-level details of the chain-flipping mechanism by using metadynamics simulations. We observe the fatty-acid chain gliding through the protein-protein interface with barely 30% of its surface exposed to water molecules. The small ACP's helix III acts as gatekeeper of the process, and we find its conformational plasticity critical for a successful substrate transfer. The results are in agreement with a wide range of experimental observations and provide unprecedented insight on the molecular determinants and driving forces of the chain-flipping process. PMID- 27409361 TI - Dispersion Corrections to the Surface Tension at Planar Surfaces. PMID- 27409362 TI - Dynamic Properties of DNA-Programmable Nanoparticle Crystallization. AB - The dynamics of DNA hybridization is very important in DNA-programmable nanoparticle crystallization. Here, coarse-grained molecular dynamics is utilized to explore the structural and dynamic properties of DNA hybridizations for a self complementary DNA-directed nanoparticle self-assembly system. The hexagonal close packed (HCP) and close-packed face-centered cubic (FCC) ordered structures are identified for the systems of different grafted DNA chains per nanoparticle, which are in good agreement with the experimental results. Most importantly, the dynamic crystallization processes of DNA hybridizations are elucidated by virtue of the mean square displacement, the percentage of hybridizations, and the lifetime of DNA bonds. The lifetime can be modeled by the DNA dehybridization, which has an exponential form. The lifetime of DNA bonds closely depends on the temperature. A suitable temperature for the DNA-nanoparticle crystallization is obtained in the work. Moreover, a too large volume fraction hinders the self assembly process due to steric effects. This work provides some essential information for future design of nanomaterials. PMID- 27409366 TI - Letters. PMID- 27409363 TI - Glomerular basement membrane thickness among the Saudi population. AB - The aim of this work was to determine the mean glomerular basement membrane (GBM) thickness in the Saudi population. We calculated the average GBM thickness in patients diagnosed with minimal change disease, and the ultrastructural analysis of at least three glomeruli was reviewed using a digital camera installed in an electron microscope. There were a total of 53 cases from 53 Saudi patients aged 2 70 years old. The mean GBM thickness for all cases was 323.6 +/- 49.5 nm. There was no significant statistical difference in the mean GBM thickness between males and females. There were significant differences in the mean GBM thickness between all age groups, except for between the age groups 18-60 and >60 years old, where GBM thickness did not differ significantly. Age was significantly correlated with definite progression or diminution in the thickness of the GBM. The mean GBM thickness in our Saudi sample population was comparable to the very few reported measurements in the literature. There was no significant association between GBM thickness and gender; however, GBM thickness is directly proportional to age, up to 60 years old. PMID- 27409364 TI - Biochemical markers of bone metabolism during early orthodontic tooth movement with aligners. AB - OBJECTIVE: To evaluate the expression of receptor activator of nuclear factor kappa ligand (RANKL), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1beta (IL-1beta), and transforming growth factor beta1 (TGF-beta1) in the gingival crevicular fluid (GCF) of teeth subjected to orthodontic forces released by aligners. MATERIALS AND METHODS: A total of 10 healthy, adult patients were selected to participate in this split-mouth study. The treatment plan was designed to obtain only one movement with the first aligner: distalization of a second molar. GCF samples were obtained from pressure and tension sites of the test tooth and from the mesiobuccal and distobuccal sites of the control tooth. The GCF sample volumes were measured using a Periotron 8000. Levels of TGF-beta, IL-1beta, RANKL, OPG, and OPN were measured by enzyme-linked immunosorbent assay. RESULTS: IL-1beta showed a significant increase at the pressure sites after 1 week and 3 weeks with respect to baseline (P < .05) compared with control sites. The kinetics of TGF-1beta and OPN were characterized by a significant increase at the tension sites of the test teeth (P < .05) after 3 weeks from the application of orthodontic force. The RANKL level was significantly increased at pressure and tension sites after 1 hour and after 1 week from the application of the orthodontic forces (P = .023 and P = .043, respectively). CONCLUSIONS: An increased concentration of bone modeling and remodeling mediators at the pressure sites (IL-1beta, RANKL) and tension sites (TGF-1beta, OPN) was observed. These scenarios are compatible with previous in vivo and in vitro studies investigating the biological effects of orthodontic tooth movement. PMID- 27409367 TI - Brief reports. PMID- 27409368 TI - Scanning sports. PMID- 27409370 TI - Hazelden: Putting Athletes' Drug Abuse in Perspective. AB - The National Football League's drug abuse program is overseen by the Hazelden Foundation, a rural Minnesota treatment center that offers a strong antidote to the 'bright lights and glory' NFL life-style. PMID- 27409369 TI - Restoring a Child's Faith. PMID- 27409373 TI - Eliminate Boxing Gloves. PMID- 27409374 TI - Musculoskeletal and Cardiopulmonary Characteristics of the Professional Ballet Dancer. AB - In brief: Sixteen professional ballet dancers from the Ohio Ballet in Akron were x-rayed, tested on a Cybex dynamometer, and tested for maximal aerobic power on a treadmill to determine musculoskeletal and cardiopulmonary capabilities. The x rays indicated that the dancers had metatarsal abnormalities characteristic of such artists. The Cybex data were considered normal for the knee. The dancers had higher than normal cardiopulmonary capacity, although it was still in the range of nonendurance athletes. PMID- 27409375 TI - How I Manage Ingrown Toenails. AB - In brief: An ingrown toenail is one of the most common diseases of the nail. Initial treatment includes trimming away the ingrown area and soaking the foot in Epsom salt, or a combination of Epsom salt and pHisoHex or Betadine. If inflammation, localized cellulitis, and pain do not resolve rapidly, chemocautery with phenol or a surgical partial matricectomy can be carried out. PMID- 27409376 TI - Hockey: Optimizing Performance and Safety. AB - In brief: A panel of physiologists, orthopedists, and a physical therapist discuss hockey performance, training, injuries, and equipment. Heart rate monitoring, muscle biopsies, and analyses of the physiological demands of hockey show that training with short work/rest ratios and practicing skills before endurance will optimize performance. Most injuries occur during games vs practice, and the incidence is higher at the beginning of the season due to lack of conditioning and inadequate equipment. Injuries increase again at the end of the season because of the fierce competition for play-off positions. PMID- 27409377 TI - Side Effects of Anabolic Steroids in Weight-Trained Men. AB - In brief: This study documents the patterns of use of anabolic steroids in 32 body builders and power lifters. These subjects and seven control athletes who had never used steroids were interviewed and underwent a medical examination including 28 diagnostic blood tests and a urinalysis. Gynecomastia was detected in 4 of the 20 current users and 1 of the other 19 subjects. Sixty-seven percent of users reported temporary changes in libido, and 56% reported a temporary increase in irritability or aggressive behavior. Physicians should tell patients about the possible adverse side effects of such agents. PMID- 27409378 TI - Blood Glucose Regulation in an Insulin-Dependent Diabetic Backpacker. AB - In brief: Glucose regulation in an insulin-dependent diabetic man during a six day backpacking trip was compared to six days at home, where he ran about 5 miles daily. The energy expenditure of backpacking was estimated from an equation based on total weight (body plus pack), and the energy cost of running was determined from heart rate-oxygen uptake relationship. Insulin dosage was the same throughout, and food intake was altered to match the additional energy expenditure. Blood glucose values taken four times each day fluctuated less at home than in the mountains, but most mean values were consistent with recommended criteria for good diabetic control. PMID- 27409379 TI - Is More Better? Another Look at ACSM. AB - Growth and diversity. Sounds like an investment plan. And maybe It is-for members of the American College of Sports Medicine. PMID- 27409381 TI - Hip Pointer Padding for Women. PMID- 27409380 TI - Wilderness Seminars: Rugged Adventure. AB - Programs run by the National Outdoor Leadership School offer participants the chance to learn how to be comfortable with the winter wilderness. PMID- 27409382 TI - How to Become a Sports Medicine Physician. AB - Dr. Virgin, a dedicated team physician, warns against succumbing to the pressures of coaches, parents, and fans when diagnosing and treating injured players during games. PMID- 27409383 TI - Names and faces. PMID- 27409385 TI - The Myth of Electrical Exercise. PMID- 27409387 TI - An fMRI and effective connectivity study investigating miss errors during advice utilization from human and machine agents. AB - As society becomes more reliant on machines and automation, understanding how people utilize advice is a necessary endeavor. Our objective was to reveal the underlying neural associations during advice utilization from expert human and machine agents with fMRI and multivariate Granger causality analysis. During an X ray luggage-screening task, participants accepted or rejected good or bad advice from either the human or machine agent framed as experts with manipulated reliability (high miss rate). We showed that the machine-agent group decreased their advice utilization compared to the human-agent group and these differences in behaviors during advice utilization could be accounted for by high expectations of reliable advice and changes in attention allocation due to miss errors. Brain areas involved with the salience and mentalizing networks, as well as sensory processing involved with attention, were recruited during the task and the advice utilization network consisted of attentional modulation of sensory information with the lingual gyrus as the driver during the decision phase and the fusiform gyrus as the driver during the feedback phase. Our findings expand on the existing literature by showing that misses degrade advice utilization, which is represented in a neural network involving salience detection and self processing with perceptual integration. PMID- 27409389 TI - Editor's mail. PMID- 27409388 TI - Coming in postgraduate medicine. PMID- 27409390 TI - Problems Solutions. PMID- 27409391 TI - What's happening in medicine. PMID- 27409392 TI - Washington Background. PMID- 27409393 TI - Physician-at-Large. PMID- 27409397 TI - Therapeutic Index to Advertisers. PMID- 27409394 TI - Infectious Process Complicating Renal Transplantation. PMID- 27409398 TI - Citrinin in cereals and feedstuffs coming from Croatia and Bosnia & Herzegovina. AB - The aim of this study was to investigate the occurrence of citrinin in different cereals (n = 341) and feedstuffs (n = 67) coming from farms and feed factories established in Croatia and Bosnia & Herzegovina. The highest mean citrinin concentration (103 +/- 102 ug/kg) was observed in cereals sampled in Bosnia & Herzegovina during 2014, although significantly different levels between the two countries were not observed. Across the cereal samples, the maximal citrinin concentration was determined in wheat (429 ug/kg), while across the feedstuffs, the highest concentration was found in pig feed (63 ug/kg). Despite of the increased citrinin levels found in some samples, especially wheat, the obtained values cannot be compared against the maximum limits, since no such levels are stipulated under the applicable legislation. But, given that data on citrinin are very scarce, they can serve as an indicator of cereal and feed contamination in this part of Europe. PMID- 27409399 TI - Findings made in gene panel to whole genome sequencing: data, knowledge, ethics - and consequences? AB - INTRODUCTION: Improvements in sequencing technologies have helped to refine diagnosis and patient stratification via molecular genetic testing for a number of conditions. Consequently, sequencing has increasingly entered clinical routine. Reduced cost, combined with enhanced throughput has helped to place sequencing also in the commercial market thus moving beyond particular indications. Diverse kinds of sequencing approaches are applied, ranging from gene panel to whole-genome sequencing. All these have proven successful in the identification of causal and therapeutically relevant alterations to the benefit of patients. However, a number of technical and ethical issues induce challenges that require their appreciation, societal discussion and consensual decision. Areas covered: In the following paper, advantages and disadvantages of different DNA sequencing strategies towards their application within and outside a clinical context are discussed particularly in the light of the incidence and impact genetic findings have at the personal as well as societal level. Expert commentary: We regard the comprehensive education of citizens about these challenges a prerequisite to reach a societal consensus on the exploitation of the huge opportunities while not neglecting the potential and real dangers that are associated with the resulting data. PMID- 27409400 TI - Association of VDR ApaI and TaqI Gene Polymorphisms with the Risk of Scleroderma and Behcet's Disease. AB - Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms have been reported in autoimmune diseases. However, their role in Behcet's disease (BD) and scleroderma remains inconclusive. Our aim was to evaluate vitamin D receptor (ApaI, TaqI) gene polymorphisms in relation to Behcet's disease and scleroderma in Egyptians. The study was conducted on 54 patients with BD, 30 scleroderma patients, and 60 healthy control subjects. VDR (ApaI, TaqI) gene polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. The "a" allele of ApaI (A/a) polymorphism was significantly associated with increased BD risk (OR = 2.09, 95% CI = 1.18-3.71, p = 0.011), while the TaqI "tt" genotype was significantly lower in BD patients as compared to control subjects (OR = 0.35, 95% CI = 0.13-0.9, p = 0.026). Carriage of "aT" VDR haplotype was significantly associated with higher BD risk (OR = 2.28, 95% = 1.14-4.56, p = 0.022). In conclusion, our findings suggest that VDR gene polymorphisms have a significant association with BD in Egyptian patients. PMID- 27409401 TI - Shape-dependent photocatalytic hydrogen evolution activity over a Pt nanoparticle coupled g-C3N4 photocatalyst. AB - Cubic, octahedral and spherical platinum (Pt) nanoparticles (NPs) ex situ supported on a graphitic carbon nitride (g-C3N4) substrate are synthesized using a colloidal adsorption-deposition method for photocatalytic hydrogen evolution reactions. These Pt NPs of different shapes have similar sizes of around 10 nm but have different facets exposed. It is found that the visible-light-driven photocatalytic activities for the Pt/g-C3N4 hybrid photocatalysts follow the order as: cubic Pt/g-C3N4 < octahedral Pt/g-C3N4 < spherical Pt/g-C3N4, revealing the significant cocatalyst shape-sensitive photocatalytic activity in the Pt/g C3N4 hybrids. This is mainly due to the different surface atomic structures of different exposed facets of Pt NPs, which lead to the disparity of active sites and adsorption energies in photocatalytic reactions. PMID- 27409403 TI - Cadmium absorption and transportation pathways in plants. AB - Controlling the uptake, transport, translocation, and accumulation of excessive amounts of cadmium from polluted environments is critical for plants and, consequently, humans with regard to food safety. Plants adopt various cellular and molecular mechanisms to minimize Cd toxicity. Upon exposure to Cd, plants initially implement avoidance strategies, such as production of organic acids, chelation, and sequestration, to prevent metal access to root cells. Nevertheless, Cd can be transported through the roots, stems, and leaves via apoplastic and symplastic pathways. These processes have been controlled by specific sites at the root surface and root cortex, in cells responsible for loading the root xylem, at the transition between the vascular systems of the root and the shoot, and in connecting tissues and cells at the stem. Although resistance to heavy metal cadmium can be achieved by either avoidance or tolerance, genetic basis to tolerance is therefore implied, in that these mechanisms are heritable attributes of tolerant mutants or genotypes. PMID- 27409404 TI - Reoperation for Recurrent Glioblastoma and Its Association With Survival Benefit. AB - BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor. Despite current treatment, recurrence is inevitable. There are no clear guidelines for treatment of recurrent glioblastoma. OBJECTIVE: To investigate factors at initial surgery predictive of reoperation, and the prognostic variables associated with survival, including reoperation for recurrence. METHODS: A retrospective cohort study was performed, including adult patients diagnosed with glioblastoma between January 2010 and December 2013. Student t test and Fisher exact test compared continuous and categorical variables between reoperation and nonreoperation groups. Univariable and Cox regression multivariable analysis was performed. RESULTS: In a cohort of 204 patients with de novo glioblastoma, 49 (24%) received reoperation at recurrence. The median overall survival in the reoperation group was 20.1 months compared with 9.0 months in the nonreoperation group (P = .001). Reoperation was associated with longer overall survival in our total population (hazard ratio, 0.646; 95% confidence interval, 0.543-0.922; P = .016) but subject to selection bias. Subgroup analyses excluding patients unlikely to be considered for reoperation suggested a much less significant effect of reoperation on survival, which warrants further study with larger cohorts. Factors at initial surgery predictive for reoperation were younger age, smaller tumor size, initial extent of resection >=50%, shorter inpatient stay, and maximal initial adjuvant therapy. When unfavorable patient characteristics are excluded, reoperation is not an independent predictor of survival. CONCLUSION: Patients undergoing reoperation have favorable prognostic characteristics, which may be responsible for the survival difference observed. We recommend that a large clinical registry be developed to better aid consistent and homogenous data collection. ABBREVIATIONS: ECOG, Eastern Cooperative Oncology GroupEOR, extent of resectionIDH-1, isocitrate dehydrogenase 1IP, inpatientMGMT, O-methylguanine methyltransferaseOS, overall survivalPFS, progression-free survivalRMH, Royal Melbourne Hospital. PMID- 27409405 TI - Commentary: Percutaneous Balloon Compression vs Percutaneous Retrogasserian Glycerol Rhizotomy for the Primary Treatment of Trigeminal Neuralgia. PMID- 27409406 TI - Commentary: Surgical Management of the Elderly With Traumatic Cervical Spinal Cord Injury: A Cost-Utility Analysis. PMID- 27409408 TI - Bone change after surgical treatment of mucous cyst at the interphalangeal joint of the great toe in a patient with rheumatoid arthritis. AB - Digital mucous cysts are a type of benign cysts of the digits, typically located at the distal interphalangeal joints or in the proximal nail fold, which usually occur on the hands. The diagnosis of digital mucous cysts is relatively easy because of its light-transmitting property, but the treatment is often difficult because of complications including recurrence, infection, diminished range of motion, and nail deformity. We report a case of rheumatoid arthritis (RA) showing good course after surgical treatment of mucous cyst at the interphalangeal joint of the great toe. In a case of RA, combination of synovectomy with surgical treatment of mucous cyst might be effective. PMID- 27409409 TI - Assessment of the origin and geothermal potential of the thermal waters by hydro isotope geochemistry: Eskisehir province, Turkey. AB - The thermal fluids vented over Eskisehir province have been investigated for their origin and to estimate the geothermal potential of the area. Thermal waters as well as bubbling and dissolved gases were collected and analysed for their chemical and isotopic features. Their isotopic composition varies in the range from -11.5 to -7.7 0/00 for delta18O, -84 and -57 0/00 for delta2H, and 0-7.2 TU for tritium. The gases (bubbling and dissolved) are mostly N2-dominated with a significant amount of CO2. The helium isotopic ratios are in the range of 0.2 0.66 R/Rac, indicate remarkable mantle-He contribution ranging between 2 and 10 % in the whole study area. Considering the estimated geothermal gradient about three times higher than the normal gradient, and the reservoir temperatures estimated to be between 50 and 100 degrees C using quartz and chalcedony geothermometers, a circulation model was built where possible mixing with shallow waters cool down the uprising geothermal fluids. PMID- 27409410 TI - Prostaglandin D2 receptor antagonists in early development as potential therapeutic options for asthma. AB - INTRODUCTION: Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that interfere with the innate inflammatory response in asthma have been identified. Promising preliminary results concern the signaling cascade promoted by prostaglandin D2 (PGD2) and its receptor antagonists. AREAS COVERED: The aim of this review is to provide the most recent clinical and preclinical data on the efficacy and safety of newly developed compounds for the treatment of allergic asthma. The authors will present an overview of the pathogenetic molecular mechanisms sustaining the chronic inflammatory response in asthma; the focus will be then directed on the mediators of the PGD2 pathway, the chemoattractant receptor-homologous molecule expressed on TH2 cells, and their latest antagonists developed. EXPERT OPINION: Bronchodilators and corticosteroids are not sufficient to achieve a satisfactory management of all asthmatic patients; the development of new specific treatments appears therefore essential. The good results in terms of cellular, functional and clinical outcomes, together with an acceptable safety of the CRTh2 antagonists represent a promising start for a tailored management of allergic asthma. PMID- 27409411 TI - A Dynamic Anesthesia System for Long-Term Imaging in Adult Zebrafish. AB - Long-term in vivo imaging in adult zebrafish (i.e., 1-24 h) has been limited by the fact that regimens for long-term anesthesia in embryos and larvae are ineffective in adults. Here, we examined the potential for dynamic administration of benzocaine to enable long-term anesthesia in adult zebrafish. We developed a computer-controlled perfusion system comprised of programmable peristaltic pumps that enabled automatic exchange between anesthetic and system water. Continuous administration of benzocaine in adult zebrafish resulted in a mean time to respiratory arrest of 5.0 h and 8-h survival of 14.3%. We measured characteristic sedation and recovery times in response to benzocaine, and used them to devise an intermittent dosing regimen consisting of 14.5 min of benzocaine followed by 5.5 min of system water. Intermittent benzocaine administration in adult zebrafish resulted in a mean time to respiratory arrest of 7.6 h and 8-h survival of 71.4%. Finally, we performed a single 24-h trial and found that intermittent dosing maintained anesthesia in an adult zebrafish over the entire 24-h period. In summary, our studies demonstrate the potential for dynamic administration of benzocaine to enable prolonged anesthesia in adult zebrafish, expanding the potential for imaging in adult physiologies that unfold over 1-24 h. PMID- 27409413 TI - Comparing Occupational Health and Safety Management System Programming with Injury Rates in Poultry Production. AB - Effective methods to reduce work-related injuries and illnesses in animal production agriculture are sorely needed. One approach that may be helpful for agriculture producers is the adoption of occupational health and safety management systems. In this replication study, the authors compared the injury rates on 32 poultry growing operations with the level of occupational health and safety management system programming at each farm. Overall correlations between injury rates and programming level were determined, as were correlations between individual management system subcomponents to ascertain which parts might be the most useful for poultry producers. It was found that, in general, higher levels of occupational health and safety management system programming were associated with lower rates of workplace injuries and illnesses, and that Management Leadership was the system subcomponent with the strongest correlation. The strength and significance of the observed associations were greater on poultry farms with more complete management system assessments. These findings are similar to those from a previous study of the dairy production industry, suggesting that occupational health and safety management systems may hold promise as a comprehensive way for producers to improve occupational health and safety performance. Further research is needed to determine the effectiveness of such systems to reduce farm work injuries and illnesses. These results are timely given the increasing focus on occupational safety and health management systems. PMID- 27409412 TI - Improved Versions of Common Estimators of the Recombination Rate. AB - The scaled recombination parameter [Formula: see text] is one of the key parameters, turning up frequently in population genetic models. Accurate estimates of [Formula: see text] are difficult to obtain, as recombination events do not always leave traces in the data. One of the most widely used approaches is composite likelihood. Here, we show that popular implementations of composite likelihood estimators can often be uniformly improved by optimizing the trade-off between bias and variance. The amount of possible improvement depends on parameters such as the sequence length, the sample size, and the mutation rate, and it can be considerable in some cases. It turns out that approximate Bayesian computation, with composite likelihood as a summary statistic, also leads to improved estimates, but now in terms of the posterior risk. Finally, we demonstrate a practical application on real data from Drosophila. PMID- 27409414 TI - Proceedings of the 2016 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Scientific Meeting : Toronto, Canada. 14-17 April 2016. PMID- 27409415 TI - Severe dyslipidemia and immune activation in HIV patients with dysglycemia. AB - BACKGROUND AND OBJECTIVE: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients is poorly understood. METHODS: We retrospectively analyzed the clinical data of 180 HIV patients, including 153 patients undergoing highly active antiretroviral therapy (HAART) and 27 HAART-naive patients. DM was defined as fasting serum glucose levels >=126 mg/dl, and impaired fasting glucose (IFG) was defined as serum glucose levels of 101-125 mg/dl at two different time points. Lipid metabolic indexes were measured. CD4+, CD8+, and CD8+ HLA-DR+ T cells were determined by flow cytometry. RESULTS: IFM and DM percentages were higher in the HAART group than in the HAART-naive group (59.5% vs. 48.1% and 21.6% vs. 7.4%, respectively; p < 0.01). Additionally, DM percentage was high in patients receiving HAART containing protease inhibitors. Serum levels of triglycerides and very low density lipoprotein cholesterol were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Serum triglyceride levels were higher in HAART-naive DM patients than in other patients (p < 0.05). CD8+ and CD8+ HLA-DR+ cell counts were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Ordinal logistic regression analysis suggested that TRIG, VLDL, CD8, and HAART were predictors of glucose metabolic disorders. CONCLUSION: HIV patients with hyperglycemia have severe dyslipidemia and immune activation, and HAART is an important impact factor of glucose and lipid metabolic disorders. PMID- 27409416 TI - Properties and cellular effects of particulate matter from direct emissions and ambient sources. AB - The pollution of particulate matter (PM) is of great concern in China and many other developing countries. It is generally recognized that the toxicity of PM is source and property dependent. However, the relationship between PM properties and toxicity is still not well understood. In this study, PM samples from direct emissions of wood, straw, coal, diesel combustion, cigarette smoking and ambient air were collected and characterized for their physicochemical properties. Their expression of intracellular reactive oxygen species (ROS) and levels of inflammatory cytokines (i.e., tumor necrosis factor-alpha (TNF-alpha)) was measured using a RAW264.7 cell model. Our results demonstrated that the properties of the samples from different origins exhibited remarkable differences. Significant increases in ROS were observed when the cells were exposed to PMs from biomass origins, including wood, straw and cigarettes, while increases in TNF-alpha were found for all the samples, particularly those from ambient air. The most important factor associated with ROS generation was the presence of water-soluble organic carbon, which was extremely abundant in the samples that directly resulted from biomass combustion. Metals, endotoxins and PM size were the most important properties associated with increases in TNF-alpha expression levels. The association of the origins of PM particles and physicochemical properties with cytotoxic properties is illustrated using a cluster analysis. PMID- 27409417 TI - Relationship between the presence of videolaryngoscopic signs suggestive of laryngopharyngeal reflux and voice disorders in teachers. AB - OBJECTIVE: To analyze the relationship between the presence of videolaryngoscopic signs suggestive of laryngopharyngeal reflux (LPR) and voice disorder (VD) in teachers. METHODS: this is a cross-sectional study with convenience sample and inclusion criteria as subjects 18 years or older, be a teacher female, seek care with complaint of VD and/or LPR. The exclusion criteria included smoking and presence of respiratory changes. All subjects concluded the following instruments: Vocal Production Condition - Teacher (VPC-T), including the Screening Index for Voice Disorder (SIVD); and Voice Handicap Index (VHI). Speech samples were collected for voice perceptual assessment and all of them were submitted to otorhinolaryngology review. RESULTS: We evaluated 121 teachers, with a mean age of 43 years and 7.8 class hours per day. Only 24.0% of the teachers did not have vocal cord lesions and 42.1% had videolaryngoscopic signs suggestive of LPR. In the group of teachers with presence of Signs suggestive of LPR, the most common symptoms of SIVD were dry throat, hoarseness, throat clearing; the average VHI was 17.9 points. There was no association between voice disorder and presence of videolaryngoscopic signs suggestive of LPR. The independent factors for the LPR in the multiple binary logistic regression analysis were age and VHI score (tertile: 13-20). CONCLUSION: There was no association between VD and LPR, but between age and VHI score. PMID- 27409418 TI - Cross-cultural adaptation of the Brazilian version of the 'Questionnaire Des Symptomes Vocaux'. AB - PURPOSE: This article aims to present the cultural equivalence of the Brazilian version of the 'Questionnaire des Symptomes Vocaux' (QSV). METHODS: The questionnaire was translated into Portuguese by two Brazilian bilingual speech language pathologists who were informed about the purpose of this research. The back translation was performed by a third bilingual Brazilian speech-language pathologist, who was also a French teacher and had not participated in the previous stage. After the comparison of translations, a final version of the questionnaire was produced and called 'Questionario de Sintomas Vocais Pediatrico (QSV-P)', which was administered to 32 individuals (16 children/adolescents with vocal complaints and their parents). The inclusion criterion was the vocal complaint and/or vocal quality altered on the perceptual auditory evaluation. The option "not applicable" was added to each item of the protocol. RESULTS: During the process of translation and cultural adaptation, no item was changed and/or eliminated from the questions. The QSV-P kept the same structure as the original French version with 31 questions, which can be responded by children/adolescents (6-18 years) and their parents, regarding the physical, emotional and social functioning of the vocal problem. CONCLUSION: The cultural equivalence of the Brazilian version of the 'Questionnaire des Symptomes Vocaux', entitled 'Questionario de Sintomas Vocais Pediatrico', was demonstrated. The QSV-P validation is currently being done. PMID- 27409419 TI - Influence of speech sample on perceptual rating of hypernasality. AB - PURPOSE: To investigate the influence of speech sample of spontaneous conversation or sentences repetition on intra and inter-rater hypernasality reliability. METHODS: One hundred and twenty audio recorded speech samples (60 containing spontaneous conversation and 60 containing repeated sentences) of individuals with repaired cleft palate+/-lip, both genders, aged between 6 and 52 years old (mean=21+/-10) were selected and edited. Three experienced speech and language pathologists rated hypernasality according to their own criteria using 4 point scale: 1=absence of hypernasality, 2=mild hypernasality, 3=moderate hypernasality and 4=severe hypernasality, first in spontaneous speech samples and 30 days after, in sentences repetition samples. Intra- and inter-rater agreements were calculated for both speech samples and were statistically compared by the Z test at a significance level of 5%. RESULTS: Comparison of intra-rater agreements between both speech samples showed an increase of the coefficients obtained in the analysis of sentences repetition compared to those obtained in spontaneous conversation. Comparison between inter-rater agreement showed no significant difference among the three raters for the two speech samples. CONCLUSION: Sentences repetition improved intra-raters reliability of perceptual judgment of hypernasality. However, the speech sample had no influence on reliability among different raters. PMID- 27409420 TI - Efficacy of trastuzumab beyond progression in HER2 positive advanced gastric cancer: a multicenter prospective observational cohort study. AB - INTRODUCTION: Trastuzumab plus chemotherapy is the standard first-line regimen in HER2 positive advanced gastric cancer (AGC), but lack of data in post-progression treatment. So, it is worth evaluating the efficacy of continuing trastuzumab after failure of the first-line trastuzumab based treatment. METHODS: 59 patients were enrolled from Zhongshan Hospital Fudan University, Sun Yat-sen University Cancer Center and Peking University Cancer Hospital between September 2012 and Oct 2015. Patients were divided into two groups according to the second line regimens: with or without trastuzumab. The primary endpoint was progression free survival of second line therapy (PFS2). Secondary end points included overall survival (OS), response rate, and adverse events (AEs). RESULTS: Baseline factors were well balanced between two groups. 32 patients treated with trastuzumab plus second line chemotherapy (group A) and 27 patients received chemotherapy alone (group B). The median follow-up time was 7.60 months (range 1.50-32.50). Longer median PFS2 was observed in group A than in group B (3.1 vs 2.0 months, P=0.008). There was no significant differences of median OS2 calculating from the second line therapy (10.5 vs 6.5 months, P=0.172) between two groups. Response rate was 9.3% in group A compared with 3.7% in group B (P=0.617). AEs were similar in two groups including cardiac safety. Subgroup analysis showed that factors of male, age<65, good performance status, HER2 immunohistochemical (IHC) 2+ and poor response to first line indicated superior PFS2 in patients continuing trastuzumab to those treated with chemotherapy alone. CONCLUSION: Continuing treatment of trastuzumab beyond first line therapy progression showed effective and safe in AGC. PMID- 27409422 TI - 14-3-3zeta and aPKC-iota synergistically facilitate epithelial-mesenchymal transition of cholangiocarcinoma via GSK-3beta/Snail signaling pathway. AB - Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3zeta and atypical protein kinase C-iota (aPKC-iota) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3 3zeta and aPKC-iota co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3beta)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3zeta and aPKC-iota was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3zeta and aPKC-iota expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3zeta and aPKC-iota. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3zeta and aPKC-iota regulated each other. In addition, 14-3-3zeta and aPKC-iota pretreatment by si-RNA inhibit the phosphorylated GSK-3beta and Snail expression during EMT. Meanwhile, silence of 14-3-3zeta or aPKC-iota suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3zeta and aPKC-iota synergistically facilitate EMT of CCA via GSK-3beta/Snail signalling pathway, and may be potential therapeutic target for CCA. PMID- 27409423 TI - Altered phenotypic and functional characteristics of CD3+CD56+ NKT-like cells in human gastric cancer. AB - CD3+CD56+ natural killer T (NKT)-like cells are a group of CD3+ T cells sharing characteristics of NK and T cells and constitute a major component of host anti tumor immune response in human cancer. However, the nature, function and clinical relevance of CD3+CD56+ NKT-like cells in human gastric cancer (GC) remain unclear. In this study, we showed that the frequencies of CD3+CD56+NKT-like cells in GC tumors were significantly decreased and low levels of tumor-infiltrating CD3+CD56+ NKT-like cells were positively correlated with poor survival and disease progression. Most CD3+CD56+NKT-like cells in GC tumors were CD45RA-CD27+/ central/effector-memory cells with decreased activity and lower expression levels of CD69, NKG2D and DNAM-1 than those in non-tumor tissues. We further observed that tumor-infiltrating CD3+CD56+ NKT-like cells had impaired effector function as shown by decreased IFN-gamma, TNF-alpha, granzyme B and Ki-67 expression. Moreover, in vitro studies showed that soluble factors released from GC tumors could induce the functional impairment of CD3+CD56+ NKT-like cells. Collectively, our data indicate that decreased tumor-infiltrating CD3+CD56+ NKT like cells with impaired effector function are associated with tumor progression and poor survival of GC patients, which may contribute to immune escape of GC. PMID- 27409426 TI - Focused fields of given power with maximum longitudinal electric field component inside a substrate. AB - Closed formulas are presented for the electromagnetic field of given power in the lens pupil, which maximizes the longitudinal electric field when focusing through an interface at arbitrary depth along the optical axis. The optimum pupil field is found to be a continuous, monotonously increasing function of the radial pupil coordinate, which differs considerably from the commonly used annular illumination. Several cases of pupil fields and focused fields are shown for different materials, NA, and focusing depth. Also, the effect of absorbing media is considered. PMID- 27409424 TI - Identification of a circulating microRNA signature to distinguish recurrence in breast cancer patients. AB - There is an urgent need for novel noninvasive prognostic biomarkers for monitoring the recurrence of breast cancer. The purpose of this study is to identify circulating microRNAs that can predict breast cancer recurrence. We conducted a microRNA profiling experiment in serum samples from 48 breast cancer patients using Exiqon miRCURY microRNA RT-PCR panels. Significantly differentiated miRNAs for recurrence in the discovery profiling were further validated in an independent set of sera from 20 patients with breast cancer recurrences and 22 patients without recurrences. We identified seven miRNAs that were differentially expressed between breast cancer patients with and without recurrences, including four miRNAs upregulated (miR-21-5p, miR-375, miR-205-5p, and miR-194-5p) and three miRNAs downregulated (miR-382-5p, miR-376c-3p, and miR 411-5p) for recurrent patients. Using penalized logistic regression, we built a 7 miRNA signature for breast cancer recurrence, which had an excellent discriminating capacity (concordance index=0.914). This signature was significantly associated with recurrence after adjusting for known prognostic factors, and it was applicable to both hormone-receptor positive (concordance index=0.890) and triple-negative breast cancers (concordance index=0.942). We also found the 7-miRNA signature were reliably measured across different runs of PCR experiments (intra-class correlation coefficient=0.780) and the signature was significantly higher in breast cancer patients with recurrence than healthy controls (p=1.1x10-5). In conclusion, circulating miRNAs are promising biomarkers and the signature may be developed into a minimally invasive multi-marker blood test for continuously monitoring the recurrence of breast cancer. It should be further validated for different subtypes of breast cancers in longitudinal studies. PMID- 27409425 TI - Multiparameter comparative analysis reveals differential impacts of various cytokines on CART cell phenotype and function ex vivo and in vivo. AB - Exogenous cytokines are widely applied to enhance the anti-tumor ability of immune cells. However, systematic comparative studies of their effects on chimeric antigen receptor (CAR)-engineered T (CART) cells are lacking. In this study, CART cells targeting folate receptor-alpha were generated and expanded ex vivo in the presence of different cytokines (IL-2, IL-7, IL-15, IL-18, and IL 21), and their expansion, phenotype and cytotoxic capacity were evaluated, in vitro and in vivo. Moreover, the effect of the administration of these cytokines along with CART cells in vivo was also studied. IL-2, IL-7, and IL-15 favored the ex vivo expansion of CART cells compared to other cytokines or no cytokine treatment. IL-7 induced the highest proportion of memory stem cell-like CART cells in the final product, and IL-21 supported the expansion of CART cells with a younger phenotype, while IL-2 induced more differentiated CART cells. IL-2 and IL-15-exposed CART cells secreted more proinflammatory cytokines and presented stronger tumor-lysis ability in vitro. However, when tested in vivo, CART cells exposed to IL-2 ex vivo showed the least anti-tumor effect. In contrast, the administration of IL-15 and IL-21 in combination with CART cells in vivo increased their tumor killing capacity. According to our results, IL-7 and IL-15 show promise to promote ex vivo expansion of CART cells, while IL-15 and IL-21 seem better suited for in vivo administration after CART cell infusion. Collectively, these results may have a profound impact on the efficacy of CART cells in both hematologic and solid cancers. PMID- 27409427 TI - Always-on low-power optical system for skin-based touchless machine control. AB - Embedded vision systems are smart energy-efficient devices that capture and process a visual signal in order to extract high-level information about the surrounding observed world. Thanks to these capabilities, embedded vision systems attract more and more interest from research and industry. In this work, we present a novel low-power optical embedded system tailored to detect the human skin under various illuminant conditions. We employ the presented sensor as a smart switch to activate one or more appliances connected to it. The system is composed of an always-on low-power RGB color sensor, a proximity sensor, and an energy-efficient microcontroller (MCU). The architecture of the color sensor allows a hardware preprocessing of the RGB signal, which is converted into the rg space directly on chip reducing the power consumption. The rg signal is delivered to the MCU, where it is classified as skin or non-skin. Each time the signal is classified as skin, the proximity sensor is activated to check the distance of the detected object. If it appears to be in the desired proximity range, the system detects the interaction and switches on/off the connected appliances. The experimental validation of the proposed system on a prototype shows that processing both distance and color remarkably improves the performance of the two separated components. This makes the system a promising tool for energy efficient, touchless control of machines. PMID- 27409428 TI - Propagation properties of Airy-Gaussian vortex beams through the gradient-index medium. AB - Propagation of Airy-Gaussian vortex (AiGV) beams through the gradient-index medium is investigated analytically and numerically with the transfer matrix method. Deriving the analytic expression of the AiGV beams based on the Huygens diffraction integral formula, we obtain the propagate path, intensity and phase distributions, and the Poynting vector of the first- and second-order AiGV beams, which propagate through the paraxial ABCD system. The ballistic trajectory is no longer conventional parabolic but trigonometric shapes in the gradient-index medium. Especially, the AiGV beams represent the singular behavior at the propagation path and the light intensity distribution. The phase distribution and the Poynting vector exhibit in reverse when the AiGV beams through the singularity. As the order increases, the main lobe of the AiGV beams is gradually overlapped by the vortex core. Further, the sidelobe weakens when the AiGV beams propagate nearly to the singularity. Additionally, the figure of the Poynting vector of the AiGV beams proves the direction of energy flow corresponding to the intensity distribution. The vortex of the second-order AiGV beams is larger, and the propagation velocity is faster than that of the first order. PMID- 27409429 TI - Omnidirectional transformation-optics cloak made from lenses and glenses. AB - We present a design for an omnidirectional transformation-optics (TO) cloak comprising thin lenses and glenses (generalized thin lenses) [J. Opt. Soc. Am. A33, 962 (2016)1084-7529JOAOD610.1364/JOSAA.33.000962]. It should be possible to realize such devices in pixelated form. Our design is a piecewise nonaffine generalization of piecewise affine pixelated-TO devices [Proc. SPIE9193, 91931E (2014)PSISDG0277-786X10.1117/12.2061404; J. Opt18, 044009 (2016)]. It is intended to be a step in the direction of TO devices made entirely from lenses, which should be readily realizable on large length scales and for a broad range of wavelengths. PMID- 27409430 TI - Aperture averaging in multiple-input single-output free-space optical systems using partially coherent radial array beams. AB - Multiple-input single-output (MISO) techniques are employed in free-space optical (FSO) links to mitigate the degrading effects of atmospheric turbulence. In this paper, for the MISO FSO system, a partially coherent radial array and a finite sized receiver aperture are used at the transmitter and the receiver, respectively. Using the extended Huygens-Fresnel principle, we formulate the average power and the power correlation at the finite-sized slow detector in weak atmospheric turbulence. System performance indicators such as the power scintillation index and the aperture averaging factor are determined. Effects of the source size, ring radius, receiver aperture radius, link distance, and structure constant and the degree of source coherence are analyzed on the performance of the MISO FSO system. In the limiting cases, the numerical results are found to be the same when compared to the existing coherent and partially coherent Gaussian beam scintillation indices. PMID- 27409431 TI - Colorimetric analysis of outdoor illumination across varieties of atmospheric conditions. AB - Solar illumination at ground level is subject to a good deal of change in spectral and colorimetric properties. With an aim of understanding the influence of atmospheric components and phases of daylight on colorimetric specifications of downward radiation, more than 5,600,000 spectral irradiance functions of daylight, sunlight, and skylight were simulated by the radiative transfer code, SBDART [Bull. Am. Meteorol. Soc.79, 2101 (1998)], under the atmospheric conditions of clear sky without aerosol particles, clear sky with aerosol particles, and overcast sky. The interquartile range of the correlated color temperatures (CCT) for daylight indicated values from 5712 to 7757 K among the three atmospheric conditions. A minimum CCT of ~3600 K was found for daylight when aerosol particles are present in the atmosphere. Our analysis indicated that hemispheric daylight with CCT less than 3600 K may be observed in rare conditions in which the level of aerosol is high in the atmosphere. In an atmosphere with aerosol particles, we also found that the chromaticity of daylight may shift along the green-purple direction of the Planckian locus, with a magnitude depending on the spectral extinction by aerosol particles and the amount of water vapor in the atmosphere. The data analysis showed that an extremely high value of CCT, in an atmosphere without aerosol particles, for daylight and skylight at low sun, is mainly due to the effect of Chappuis absorption band of ozone at ~600 nm. In this paper, we compare our data with well-known observations from previous research, including the ones used by the CIE to define natural daylight illuminants. PMID- 27409432 TI - Design of channeled partial Mueller matrix polarimeters. AB - In this paper, we introduce a novel class of systems called channeled partial Mueller matrix polarimeters (c-pMMPs). Their analysis benefits greatly by drawing from the concepts of generalized construction of channeled polarimeters as described by the modulation matrix. The modulation matrix resembles that of the data reduction method of a conventional polarimeter, but instead of using Mueller vectors as the bases, attention is focused on the Fourier properties of the measurement conditions. By leveraging the understanding of the measurement's structure, its decomposition can be manipulated to reveal noise resilience and information about the polarimeter's ability to measure the aspect of polarization that are important for any given task. We demonstrate the theory with a numerical optimization that designs c-pMMPs for the task of monitoring the damage state of a material as presented earlier by Hoover and Tyo [Appl. Opt.46, 8364 (2007)APOPAI0003-693510.1364/AO.46.008364]. We select several example systems that produce a fewer-than-full-system number of channels yet retain the ability to discriminate objects of interest. Their respective trade-offs are discussed. PMID- 27409433 TI - Polarization oscillations of near-field thermal emission. AB - We consider the polarization of thermal emission in the near field of various materials, including dielectrics and metallic systems with resonant surface modes. We find that, at thermal equilibrium, the degree of polarization exhibits spatial oscillations with a period of approximately half the optical wavelength, independent of material composition. This result contrasts with that of Setala et al. [Phys. Rev. Lett.88, 123902 (2002)PRLTAO0031 900710.1103/PhysRevLett.88.123902], who find monotonic decay of the degree of polarization for systems in local thermal equilibrium. PMID- 27409434 TI - Hue-preserving and saturation-improved color histogram equalization algorithm. AB - In this paper, an algorithm is proposed to improve contrast and saturation without color degradation. The local histogram equalization (HE) method offers better performance than the global HE method, whereas the local HE method sometimes produces undesirable results due to the block-based processing. The proposed contrast-enhancement (CE) algorithm reflects the characteristics of the global HE method in the local HE method to avoid the artifacts, while global and local contrasts are enhanced. There are two ways to apply the proposed CE algorithm to color images. One is luminance processing methods, and the other one is each channel processing methods. However, these ways incur excessive or reduced saturation and color degradation problems. The proposed algorithm solves these problems by using channel adaptive equalization and similarity of ratios between the channels. Experimental results show that the proposed algorithm enhances contrast and saturation while preserving the hue and producing better performance than existing methods in terms of objective evaluation metrics. PMID- 27409435 TI - Improving the axial and lateral resolution of three-dimensional fluorescence microscopy using random speckle illuminations. AB - We consider a fluorescence microscope in which several three-dimensional images of a sample are recorded for different speckle illuminations. We show, on synthetic data, that by summing the positive deconvolution of each speckle image, one obtains a sample reconstruction with axial and transverse resolutions that compare favorably to that of an ideal confocal microscope. PMID- 27409436 TI - Spectral imaging using consumer-level devices and kernel-based regression. AB - Hyperspectral reflectance factor image estimations were performed in the 400-700 nm wavelength range using a portable consumer-level laptop display as an adjustable light source for a trichromatic camera. Targets of interest were ColorChecker Classic samples, Munsell Matte samples, geometrically challenging tempera icon paintings from the turn of the 20th century, and human hands. Measurements and simulations were performed using Nikon D80 RGB camera and Dell Vostro 2520 laptop screen as a light source. Estimations were performed without spectral characteristics of the devices and by emphasizing simplicity for training sets and estimation model optimization. Spectral and color error images are shown for the estimations using line-scanned hyperspectral images as the ground truth. Estimations were performed using kernel-based regression models via a first-degree inhomogeneous polynomial kernel and a Matern kernel, where in the latter case the median heuristic approach for model optimization and link function for bounded estimation were evaluated. Results suggest modest requirements for a training set and show that all estimation models have markedly improved accuracy with respect to the DE00 color distance (up to 99% for paintings and hands) and the Pearson distance (up to 98% for paintings and 99% for hands) from a weak training set (Digital ColorChecker SG) case when small representative training data were used in the estimation. PMID- 27409437 TI - Generalized beam quality factor of aberrated truncated Gaussian laser beams: erratum. AB - A correction is given for Eqs. (10a) and (10b) [J. Opt. Soc. Am. A28, 1372 (2011)JOAOD60740-323210.1364/JOSAA.28.001372]. PMID- 27409439 TI - Closed fringe demodulation using phase decomposition by Fourier basis functions. AB - We report a new technique for the demodulation of a closed fringe pattern by representing the phase as a weighted linear combination of a certain number of linearly independent Fourier basis functions in a given row/column at a time. A state space model is developed with the weights of the basis functions as the elements of the state vector. The iterative extended Kalman filter is effectively utilized for the robust estimation of the weights. A coarse estimate of the fringe density based on the fringe frequency map is used to determine the initial row/column to start with and subsequently the optimal number of basis functions. The performance of the proposed method is evaluated with several noisy fringe patterns. Experimental results are also reported to support the practical applicability of the proposed method. PMID- 27409438 TI - General analytical expressions for the impact of polarization aberration on lithographic imaging under linearly polarized illumination. AB - With the shrinking of the critical dimension, the impact of polarization aberration on lithographic imaging becomes increasingly prominent. In this paper, the linear relationships between the image placement error and odd Pauli-Zernike polarization aberrations, as well as those between the best focus shift and even Pauli-Zernike polarization aberrations, are established by analyzing the imaging of the alternating phase-shifting mask. The relational expressions of the polarization aberration sensitivities (PAS) and the polarization angle of illumination are obtained based on these linear relationships. Then the expressions for the zero-value points and extremum points of the PAS are derived, and the impact of the polarization angle of illumination on the PAS is analyzed. The derived analytical expressions match the simulation results well; these can be used to analyze the detrimental impact of polarization aberration on lithographic imaging and provide a theoretical basis for exploring polarization aberration measurement and control techniques. PMID- 27409440 TI - First-principles definition and measurement of planetary electromagnetic-energy budget. AB - The imperative to quantify the Earth's electromagnetic-energy budget with an extremely high accuracy has been widely recognized but has never been formulated in the framework of fundamental physics. In this paper we give a first-principles definition of the planetary electromagnetic-energy budget using the Poynting vector formalism and discuss how it can, in principle, be measured. Our derivation is based on an absolute minimum of theoretical assumptions, is free of outdated notions of phenomenological radiometry, and naturally leads to the conceptual formulation of an instrument called the double hemispherical cavity radiometer (DHCR). The practical measurement of the planetary energy budget would require flying a constellation of several dozen planet-orbiting satellites hosting identical well-calibrated DHCRs. PMID- 27409441 TI - Large color gamut displays with diffraction gratings. AB - The ability to display a broad variety of colors has great benefits not only in the context of entertainment but also as a means to streamline design in prototyping and manufacturing processes. Displays that use RGB filters or backlights cannot span all colors that occur in nature. To improve the accuracy of color reproduction, there have been attempts to include additional color primaries in displays. Existing solutions, however, have an impact on cost, scalability, and spatial resolution and are predominantly applicable to projection systems. We propose an approach based on combining diffraction grating extractors and the HANS imaging pipeline initially developed for printing. This combination offers unprecedented potential to attain large color gamuts with the same backlights commercially used today. PMID- 27409442 TI - Classical theory of thermal radiation from a solid. AB - In this work, a solid at a finite temperature is modeled as an ensemble of identical atoms, each of which moves around a lattice site inside an isotropic harmonic potential. The motion of one such atom is studied first. It is found that the atom moves like a time-dependent current density and, thus, can emit electromagnetic radiation. Since all the atoms are identical, they can radiate, too. The resultant radiation from the atoms is the familiar thermal radiation from the solid. After its general expression is obtained, the intensity of the thermal radiation is discussed for its properties, and specifically calculated in the low-temperature limit. Both atomic motion and radiation are formulated in the classical domain. PMID- 27409443 TI - Application of the Quanta image sensor concept to linear polarization imaging-a theoretical study. AB - Research efforts in linear polarization imaging have largely targeted the development of novel polarizing filters with improved performance and the monolithic integration of image sensors and polarization filter arrays. However, as pixel sizes in CMOS image sensors continue to decrease, the same limitations that have an impact on color and monochrome CMOS image sensors will undoubtedly affect polarization imagers. Issues of low signal capacity and dynamic range in small pixels will severely limit the useful polarization information that can be obtained. In this paper, we propose to leverage the benefits of the relatively new Quanta image sensor (QIS) concept to mitigate the anticipated limitations of linear polarization imaging as pixel sizes decrease. We address, by theoretical calculation and simulation, implementation issues such as alignment of polarization filters over extremely small pixels used in the QIS concept and polarization image formation from single-bit output of such pixels. We also present design innovations aimed at exploiting the benefits of this new imaging concept for simultaneous color and linear polarization imaging. PMID- 27409444 TI - Visual effect of a linear Fresnel lens illuminated with a directional backlight. AB - A linear Fresnel lens illuminated by a directional backlight is studied. The light distribution on the lens surface visualized by a retina is simulated with a Monte Carlo ray-tracing technique, and the visualized display uniformity on the lens surface is found to depend critically on the lens quality as well as on the viewing position away from the light propagation axis. The effect of the light source configuration as well as the deviation of the microstructures of the Fresnel lens from ideal structure are studied. The simulation is verified with an experimental study, and good agreement between numerical and experimental results is obtained. Design guidelines are presented for a backlight-illuminated system to achieve high-quality uniform flat-panel two-dimensional and autostereoscopic displays. PMID- 27409445 TI - Security authentication with a three-dimensional optical phase code using random forest classifier. AB - An object with a unique three-dimensional (3D) optical phase mask attached is analyzed for security and authentication. These 3D optical phase masks are more difficult to duplicate or to have a mathematical formulation compared with 2D masks and thus have improved security capabilities. A quick response code was modulated using a random 3D optical phase mask generating a 3D optical phase code (OPC). Due to the scattering of light through the 3D OPC, a unique speckle pattern based on the materials and structure in the 3D optical phase mask is generated and recorded on a CCD device. Feature extraction is performed by calculating the mean, variance, skewness, kurtosis, and entropy for each recorded speckle pattern. The random forest classifier is used for authentication. Optical experiments demonstrate the feasibility of the authentication scheme. PMID- 27409446 TI - Dynamic video encryption algorithm for H.264/AVC based on a spatiotemporal chaos system. AB - Video encryption schemes mostly employ the selective encryption method to encrypt parts of important and sensitive video information, aiming to ensure the real time performance and encryption efficiency. The classic block cipher is not applicable to video encryption due to the high computational overhead. In this paper, we propose the encryption selection control module to encrypt video syntax elements dynamically which is controlled by the chaotic pseudorandom sequence. A novel spatiotemporal chaos system and binarization method is used to generate a key stream for encrypting the chosen syntax elements. The proposed scheme enhances the resistance against attacks through the dynamic encryption process and high-security stream cipher. Experimental results show that the proposed method exhibits high security and high efficiency with little effect on the compression ratio and time cost. PMID- 27409447 TI - Analytic calculation of vortex diffraction by a triangular aperture. AB - We present an analytic calculation of the diffraction of a vortex beam by a triangular aperture. This calculation is used to study the diffraction of multimode vortex beams and off-axis vortex beams. Implications of these results for the effectiveness of diffraction as a vortex detection method are discussed. PMID- 27409448 TI - Transmission tomography of forward-scattering structures. AB - A method of multiple-shot scatter correction in transmission tomography systems is considered. It is assumed that the scattering is confined within a cone of relatively small angles, and the propagation is governed by a standard parabolic wave equation. An approximate directed-wave propagator may then be obtained, which relates a set of diffraction patterns measured for a multitude of point sources, to a linogram of the object. Introducing a specially designed coordinate transformation, we rewrite this propagator in a separable form as a paired Fresnel transform. Further, a corresponding inverse operator is applied to extract emulated projections (constituting jointly a sinogram) of the object from the measured data. Apart from the original algorithm, which suffers essentially from truncation errors, its improved, considerably more robust version is also constructed. The estimated sinograms may be inverted by any of the existing methods including a filtered back-projection or algebraic reconstruction techniques. The results of simulations show an essential reduction of diffraction/scattering artifacts and improved resolution of reconstructed images. At the same time it is found that scatter correction may cause object-dependent ring artifacts observed in the tomograms. PMID- 27409449 TI - Replacement of the Lorentz law for the shape of the spectral lines in the infrared region. AB - We propose a new phenomenological law for the shape of the spectral lines in the infrared, which accounts for the exponential decay of the extinction coefficient in the high-frequency region, observed in many spectra. We apply this law to the measured infrared spectra of LiF, NaCl, and MgF2, finding good agreement over a wide range of frequencies. PMID- 27409450 TI - Contextual phase estimation from two-plane intensity measurements. AB - In this work we construct examples of paraxial light fields whose intensities defined at all points in space do not have a corresponding cross-spectrally pure field amplitude reproducing the same set of transported intensities at all transverse planes. Nevertheless, two spatially separated transverse plane intensities as drawn from these examples are shown to have a corresponding cross spectrally pure field amplitude, which, through paraxial free propagation between these two planes, reproduces the drawn transverse plane intensities. And the phase associated with such a field amplitude at a given transverse plane is found to be contextual, and intrinsically dependent on the pairing plane. PMID- 27409451 TI - Enhanced manifold regularization for semi-supervised classification. AB - Manifold regularization (MR) has become one of the most widely used approaches in the semi-supervised learning field. It has shown superiority by exploiting the local manifold structure of both labeled and unlabeled data. The manifold structure is modeled by constructing a Laplacian graph and then incorporated in learning through a smoothness regularization term. Hence the labels of labeled and unlabeled data vary smoothly along the geodesics on the manifold. However, MR has ignored the discriminative ability of the labeled and unlabeled data. To address the problem, we propose an enhanced MR framework for semi-supervised classification in which the local discriminative information of the labeled and unlabeled data is explicitly exploited. To make full use of labeled data, we firstly employ a semi-supervised clustering method to discover the underlying data space structure of the whole dataset. Then we construct a local discrimination graph to model the discriminative information of labeled and unlabeled data according to the discovered intrinsic structure. Therefore, the data points that may be from different clusters, though similar on the manifold, are enforced far away from each other. Finally, the discrimination graph is incorporated into the MR framework. In particular, we utilize semi-supervised fuzzy c-means and Laplacian regularized Kernel minimum squared error for semi supervised clustering and classification, respectively. Experimental results on several benchmark datasets and face recognition demonstrate the effectiveness of our proposed method. PMID- 27409452 TI - Optimal channels for channelized quadratic estimators. AB - We present a new method for computing optimized channels for estimation tasks that is feasible for high-dimensional image data. Maximum-likelihood (ML) parameter estimates are challenging to compute from high-dimensional likelihoods. The dimensionality reduction from M measurements to L channels is a critical advantage of channelized quadratic estimators (CQEs), since estimating likelihood moments from channelized data requires smaller sample sizes and inverting a smaller covariance matrix is easier. The channelized likelihood is then used to form ML estimates of the parameter(s). In this work we choose an imaging example in which the second-order statistics of the image data depend upon the parameter of interest: the correlation length. Correlation lengths are used to approximate background textures in many imaging applications, and in these cases an estimate of the correlation length is useful for pre-whitening. In a simulation study we compare the estimation performance, as measured by the root-mean-squared error (RMSE), of correlation length estimates from CQE and power spectral density (PSD) distribution fitting. To abide by the assumptions of the PSD method we simulate an ergodic, isotropic, stationary, and zero-mean random process. These assumptions are not part of the CQE formalism. The CQE method assumes a Gaussian channelized likelihood that can be a valid for non-Gaussian image data, since the channel outputs are formed from weighted sums of the image elements. We have shown that, for three or more channels, the RMSE of CQE estimates of correlation length is lower than conventional PSD estimates. We also show that computing CQE by using a standard nonlinear optimization method produces channels that yield RMSE within 2% of the analytic optimum. CQE estimates of anisotropic correlation length estimation are reported to demonstrate this technique on a two-parameter estimation problem. PMID- 27409453 TI - Muscle hypertrophy as the presenting sign in a patient with a complete FHL1 deletion. AB - Four and a half LIM protein 1 (FHL1/SLIM1) has recently been identified as the causative gene mutated in four distinct diseases affecting skeletal muscle that have overlapping features, including reducing body myopathy, X-linked myopathy, X linked dominant scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy. FHL1 localises to the sarcomere and the sarcolemma and is believed to participate in muscle growth and differentiation as well as in sarcomere assembly. We describe in this case report a boy with a deletion of the entire FHL1 gene who is now 15 years of age and presented with muscle hypertrophy, reduced subcutaneous fat, rigid spine and short stature. This case is the first, to our knowledge, with a complete loss of the FHL1 protein and MAP7D3 in combination. It supports the theory that dominant negative effects (accumulation of cytotoxic-mutated FHL1 protein) worsen the pathogenesis. It extends the phenotype of FHL1-related myopathies and should prompt future testing in undiagnosed patients who present with unexplained muscle hypertrophy, contractures and rigid spine, particularly if male. PMID- 27409454 TI - 2'-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA. AB - Electron paramagnetic resonance (EPR) spectroscopy is a powerful method to elucidate molecular structure through the measurement of distances between conformationally well-defined spin labels. Here we report a sequence-flexible approach to the synthesis of double spin-labeled DNA duplexes, where 2' alkynylnucleosides are incorporated at terminal and internal positions on complementary strands. Post-DNA synthesis copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with a variety of spin labels enable the use of double electron-electron resonance experiments to measure a number of distances on the duplex, affording a high level of detailed structural information. PMID- 27409455 TI - Outcomes After Anticoagulation for Traumatic Arterial Injuries of the Extremity. PMID- 27409456 TI - Modulation of Defects in Semiconductors by Facile and Controllable Reduction: The Case of p-type CuCrO2 Nanoparticles. AB - Optical and electrical characteristics of solid materials are well-known to be intimately related to the presence of intrinsic or extrinsic defects. Hence, the control of defects in semiconductors is of great importance to achieve specific properties, for example, transparency and conductivity. Herein, a facile and controllable reduction method for modulating the defects is proposed and used for the case of p-type delafossite CuCrO2 nanoparticles. The optical absorption in the infrared region of the CuCrO2 material can then be fine-tuned via the continuous reduction of nonstoichiometric Cu(II), naturally stabilized in small amounts. This reduction modifies the concentration of positive charge carriers in the material, and thus the conductive and reflective properties, as well as the flat band potential. Indeed, this controllable reduction methodology provides a novel strategy to modulate the (opto-) electronic characteristics of semiconductors. PMID- 27409457 TI - Smart Polymeric Nanocarriers of Met-enkephalin. AB - This study describes a novel approach to polymeric nanocarriers of the therapeutic peptide met-enkephalin based on the aggregation of thermoresponsive polymers. Thermoresponsive bioconjugate poly((di(ethylene glycol) monomethyl ether methacrylate)-ran-(oligo(ethylene glycol) monomethyl ether methacrylate) is synthesized by AGET ATRP using modified met-enkephalin as a macroinitiator. The abrupt heating of bioconjugate water solution leads to the self-assembly of bioconjugate chains and the formation of mesoglobules of controlled sizes. Mesoglobules formed by bioconjugates are stabilized by coating with cross-linked two-layer shell via nucleated radical polymerization of N-isopropylacrylamide using a degradable cross-linker. The targeting peptide RGD, containing the fluorescence marker carboxyfluorescein, is linked to a nanocarrier during the formation of the outer shell layer. In the presence of glutathione, the whole shell is completely degradable and the met-enkephalin conjugate is released. It is anticipated that precisely engineered nanoparticles protecting their cargo will emerge as the next-generation platform for cancer therapy and many other biomedical applications. PMID- 27409458 TI - DFT Calculations with van der Waals Interactions of Hydrated Calcium Carbonate Crystals CaCO3.(H2O, 6H2O): Structural, Electronic, Optical, and Vibrational Properties. AB - The role of hydration on the structural, electronic, optical, and vibrational properties of monohydrated (CaCO3.H2O, hexagonal, P31, Z = 9) and hexahydrated (CaCO3.6H2O, monoclinic, C2/c, Z = 4) calcite crystals is assessed with the help of published experimental and theoretical data applying density functional theory within the generalized gradient approximation and a dispersion correction scheme. We show that the presence of water increases the main band gap of monohydrocalcite by 0.4 eV relative to the anhydrous structure, although practically not changing the hexahydrocalcite band gap. The gap type, however, is modified from indirect to direct as one switches from the monohydrated to the hexahydrated crystal. A good agreement was obtained between the simulated vibrational infrared and Raman spectra and the experimental data, with an infrared signature of hexahydrocalcite relative to monohydrocalcite being observed at 837 cm(-1). Other important vibrational signatures of the lattice, water molecules, and CO3(2-) were identified as well. Analysis of the phonon dispersion curves shows that, as the hydration level of calcite increases, the longitudinal optical-transverse optical phonon splitting becomes smaller. The thermodynamics properties of hexahydrocalcite as a function of temperature resemble closely those of calcite, while monohydrocalcite exhibits a very distinct behavior. PMID- 27409459 TI - The Development, Commercialization, and Impact of Optical Coherence Tomography. AB - This review was written for the special issue of IOVS to describe the history of optical coherence tomography (OCT) and its evolution from a nonscientific, historic perspective. Optical coherence tomography has become a standard of care in ophthalmology, providing real-time information on structure and function - diagnosing disease, evaluating progression, and assessing response to therapy, as well as helping to understand disease pathogenesis and create new therapies. Optical coherence tomography also has applications in multiple clinical specialties, fundamental research, and manufacturing. We review the early history of OCT describing how research and development evolves and the important role of multidisciplinary collaboration and expertise. Optical coherence tomography had its origin in femtosecond optics, but used optical communications technologies and required advanced engineering for early OCT prototypes, clinical feasibility studies, entrepreneurship, and corporate development in order to achieve clinical acceptance and clinical impact. Critical advances were made by early career researchers, clinician scientists, engineering experts, and business leaders, which enabled OCT to have a worldwide impact on health care. We introduce the concept of an "ecosystem" consisting of research, government funding, collaboration and competition, clinical studies, innovation, entrepreneurship and industry, and impact - all of which must work synergistically. The process that we recount is long and challenging, but it is our hope that it might inspire early career professionals in science, engineering, and medicine, and that the clinical and research community will find this review of interest. PMID- 27409460 TI - Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra High Resolution OCT Imaging. AB - PURPOSE: We examined if light induces changes in the retinal structure that can be observed using optical coherence tomography (OCT). METHODS: Normal C57BL/6J mice (age 3-6 months) adapted to either room light (15 minutes to ~5 hours, 50 500 lux) or darkness (overnight) were imaged using a Bioptigen UHR-OCT system. Confocal histologic images were obtained from mice killed under light- or dark adapted conditions. RESULTS: The OCT image of eyes adapted to room light exhibited significant increases (6.1 +/- 0.8 MUm, n = 13) in total retina thickness compared to the same eyes after overnight dark adaptation. These light adapted retinal thickness changes occurred mainly in the outer retina, with the development of a hyporeflective band between the RPE and photoreceptor-tip layers. Histologic analysis revealed a light-evoked elongation between the outer limiting membrane and Bruch's membrane from 45.8 +/- 1.7 MUm in the dark (n = 5) to 52.1 +/- 3.7 MUm (n = 5) in the light. Light-adapted retinas showed an increase of actin staining in RPE apical microvilli at the same location as the hyporeflective band observed in OCT images. Elongation of the outer retina could be detected even with brief light exposures, increasing 2.1 +/- 0.3 MUm after 15 minutes (n = 9), and 4.1 +/- 1.0 MUm after 2 hours (n = 6). Conversely, dark adaptation caused outer retinal shortening of 1.4 +/- 0.4 MUm (n = 7) and 3.0 +/- 0.5 MUm (n = 8) after 15 minutes and 2 hours, respectively. CONCLUSIONS: Light adaption induces an increase in the thickness of the outer retina and the appearance of a hyporeflective band in the OCT image. This is consistent with previous reports of light-induced fluid accumulation in the subretinal space. PMID- 27409461 TI - Evaluating the Effects of Riboflavin/UV-A and Rose-Bengal/Green Light Cross Linking of the Rabbit Cornea by Noncontact Optical Coherence Elastography. AB - PURPOSE: The purpose of this study was to use noncontact optical coherence elastography (OCE) to evaluate and compare changes in biomechanical properties that occurred in rabbit cornea in situ after corneal collagen cross-linking by either of two techniques: ultraviolet-A (UV-A)/riboflavin or rose-Bengal/green light. METHODS: Low-amplitude (<=10 MUm) elastic waves were induced in mature rabbit corneas by a focused air pulse. Elastic wave propagation was imaged by a phase-stabilized swept source OCE (PhS-SSOCE) system. Corneas were then cross linked by either of two methods: UV-A/riboflavin (UV-CXL) or rose-Bengal/green light (RGX). Phase velocities of the elastic waves were fitted to a previously developed modified Rayleigh-Lamb frequency equation to obtain the viscoelasticity of the corneas before and after the cross-linking treatments. Micro-scale depth resolved phase velocity distribution revealed the depth-wise heterogeneity of both cross-linking techniques. RESULTS: Under standard treatment settings, UV-CXL significantly increased the stiffness of the corneas by ~47% (P < 0.05), but RGX did not produce statistically significant increases. The shear viscosities were unaffected by either cross-linking technique. The depth-wise phase velocities showed that UV-CXL affected the anterior ~34% of the corneas, whereas RGX affected only the anterior ~16% of the corneas. CONCLUSIONS: UV-CXL significantly strengthens the cornea, whereas RGX does not, and the effects of cross-linking by UV-CXL reach deeper into the cornea than cross-linking effects of RGX under similar conditions. PMID- 27409462 TI - Measurement of Retinal Vascular Caliber From Optical Coherence Tomography Phase Images. AB - PURPOSE: To compare retinal vessel calibers extracted from phase-sensitive optical coherence tomography (OCT) images with vessel calibers as obtained from the Retinal Vessel Analyzer (RVA). METHODS: Data from previously published studies in 13 healthy subjects breathing room air (n = 214 vessels) and 7 subjects breathing 100% oxygen (n = 101 vessels) were used. Vessel calibers from OCT phase images were measured vertically along the optical axis by three independent graders. The data from RVA fundus images were corrected for magnification to obtain absolute values. RESULTS: The average vessel diameter as obtained from OCT images during normoxia was lower than from RVA images (83.8 +/- 28.2 MUm versus 86.6 +/- 28.0 MUm, P < 0.001). The same phenomenon was observed during 100% oxygen breathing (OCT: 81.0 +/- 22.4 MUm, RVA: 85.5 +/- 26.0 MUm; P = 0.001). Although the agreement between the two methods was generally high, the difference in individual vessels could be as high as 40%. These differences were neither dependent on absolute vessel size nor preferably found in specific subjects. Interobserver differences between OCT evaluators were much lower than differences between the techniques. CONCLUSIONS: Extracting vessel calibers from OCT phase images may be an attractive approach to overcome some of the problems associated with fundus imaging. The source of differences in vessel caliber between the two methods remains to be investigated. In addition, it remains unclear whether OCT-based vessel caliber measurement is superior to fundus camera based imaging in risk stratification for systemic or ocular disease. (ClinicalTrials.gov numbers, NCT00914407, NCT02531399.). PMID- 27409463 TI - Imaging Foveal Microvasculature: Optical Coherence Tomography Angiography Versus Adaptive Optics Scanning Light Ophthalmoscope Fluorescein Angiography. AB - PURPOSE: To compare the use of optical coherence tomography angiography (OCTA) and adaptive optics scanning light ophthalmoscope fluorescein angiography (AOSLO FA) for characterizing the foveal microvasculature in healthy and vasculopathic eyes. METHODS: Four healthy controls and 11 vasculopathic patients (4 diabetic retinopathy, 4 retinal vein occlusion, and 3 sickle cell retinopathy) were imaged with OCTA and AOSLO FA. Foveal perfusion maps were semiautomatically skeletonized for quantitative analysis, which included foveal avascular zone (FAZ) metrics (area, perimeter, acircularity index) and vessel density in three concentric annular regions of interest. On each set of OCTA and AOSLO FA images, matching vessel segments were used for lumen diameter measurement. Qualitative image comparisons were performed by visual identification of microaneurysms, vessel loops, leakage, and vessel segments. RESULTS: Adaptive optics scanning light ophthalmoscope FA and OCTA showed no statistically significant differences in FAZ perimeter, acircularity index, and vessel densities. Foveal avascular zone area, however, showed a small but statistically significant difference of 1.8% (P = 0.004). Lumen diameter was significantly larger on OCTA (mean difference 5.7 MUm, P < 0.001). Microaneurysms, fine structure of vessel loops, leakage, and some vessel segments were visible on AOSLO FA but not OCTA, while blood vessels obscured by leakage were visible only on OCTA. CONCLUSIONS: Optical coherence tomography angiography is comparable to AOSLO FA at imaging the foveal microvasculature except for differences in FAZ area, lumen diameter, and some qualitative features. These results, together with its ease of use, short acquisition time, and avoidance of potentially phototoxic blue light, support OCTA as a tool for monitoring ocular pathology and detecting early disease. PMID- 27409464 TI - Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration. AB - PURPOSE: To explain the pivotal role optical coherence tomography (OCT) imaging had in the development of antiangiogenic therapies for the treatment of neovascular age-related macular degeneration (nvAMD). METHODS: A historical literature review was combined with personal perspectives from the introduction of OCT imaging and the early clinical use of vascular endothelial growth factor (VEGF) inhibitors. RESULTS: At the time that OCT emerged, the gold standard for imaging of nvAMD was fluorescein angiography (FA), a time-consuming, dye-based, invasive technique that provided en face images of the retina and was used to characterize leakage, perfusion status, and the types of macular neovascularization (MNV). In comparison, OCT imaging was a fast, safe, noninvasive technique that complemented FA imaging by providing cross-sectional images of the macula. OCT was able to visualize and quantify the macular fluid that was associated with the presence of excess VEGF, which was identified by intraretinal fluid, subretinal fluid, and fluid under the retinal pigment epithelium (RPE). Clinicians quickly appreciated the benefits of OCT imaging for following macular fluid after anti-VEGF therapy. By observing the qualitative and quantitative changes in macular fluid depicted by OCT imaging, clinicians were empowered to compare anti-VEGF drugs and move from fixed-dosing regimens to patient-specific dosing strategies requiring fewer injections. CONCLUSIONS: Optical coherence tomography imaging was adopted as a VEGF-meter, a method to detect excess VEGF, and evolved to become the gold standard imaging strategy for diagnosing nvAMD, assessing treatment responses to anti-VEGF drugs, deciding when to re-treat, and evaluating disease progression. PMID- 27409465 TI - Retinal Blood Flow Response to Hyperoxia Measured With En Face Doppler Optical Coherence Tomography. AB - PURPOSE: To use multiplane en face Doppler optical coherence tomography (OCT) to measure the change in total retinal blood flow (TRBF) in response to hyperoxia. METHODS: One eye of each healthy human participant (n = 8) was scanned with a commercial high-speed (70-kHz) spectral OCT system. Three repeated scans were captured at baseline and after 10 minutes of oxygen (hyperoxia) by open nasal mask. The procedure was performed twice on day 1 and once more on day 2. Blood flow of each vein was estimated using Doppler OCT at an optimized en face plane. The TRBF was summed from all veins at the optic disc. The TRBF hyperoxic response was calculated as the TRBF percent change from baseline. RESULTS: Participants experienced a 23.6% +/- 10.7% (mean +/- standard deviation [SD]) decrease (P < 0.001, paired t-test) in TRBF during hyperoxia. The within-day repeatability of baseline TRBF was 4.1% and the between-day reproducibility was 10.9% coefficient of variation (CV). Between-grader reproducibility was 3.9% CV. The repeatability and reproducibility (pooled SD) of hyperoxic response were 6.1% and 6.4%, respectively. CONCLUSIONS: The multiplane en face Doppler OCT algorithm was able to detect, in all participants, a decreased TRBF in response to hyperoxia. The response magnitude for each participant varied among repeated trials, and the averaging of multiple trials was helpful in establishing the individual response. This technique shows good potential for the clinical investigation of vascular autoregulation. PMID- 27409466 TI - Impact of Microscope-Integrated OCT on Ophthalmology Resident Performance of Anterior Segment Surgical Maneuvers in Model Eyes. AB - PURPOSE: The integration of swept-source optical coherence tomography (SS-OCT) into the operating microscope enables real-time, tissue-level three-dimensional (3D) imaging to aid in ophthalmic microsurgery. In this prospective randomized controlled study, we evaluated the impact of SS microscope-integrated OCT (MI OCT) on ophthalmology residents' performance of ophthalmic microsurgical maneuvers. METHODS: Fourteen ophthalmology residents from a single institution were stratified by year of training and randomized to perform four anterior segment surgical maneuvers on porcine eyes with (MI-OCT+) or without (MI-OCT-) direct intraoperative OCT guidance. Subsequently, both groups repeated the same maneuvers without MI-OCT feedback to test whether initial MI-OCT experience affected subsequent surgical performance. Finally, the MI-OCT- group was crossed over and allowed to repeat the same maneuvers with direct MI-OCT guidance. Each resident completed a survey at the completion of the study. RESULTS: With direct MI-OCT feedback, residents demonstrated enhanced performance in depth-based anterior segment maneuvers (corneal suture passes at 50% and 90% depth and corneal laceration repair) compared with the residents operating without MI-OCT. Microscope-integrated OCT+ residents continued to outperform the controls when both groups subsequently operated without MI-OCT. For clear corneal wound geometry, there was no statistically significant effect of MI-OCT as applied in this study. Overall, the resident surgeons rated their subjective experience of using MI-OCT very favorably. CONCLUSIONS: Microscope-integrated OCT feedback enhances performance of ophthalmology residents in select anterior segment surgical maneuvers. Microscope-integrated OCT represents a valuable tool in the surgical education of ophthalmology residents. PMID- 27409467 TI - Structural Changes Induced by a Corneal Shape-Changing Inlay, Deduced From Optical Coherence Tomography and Wavefront Measurements. AB - PURPOSE: Changes to the anterior stroma and epithelium induced by a meniscus shaped corneal inlay are presented. The hypothesis that local curvature is a driver of epithelial remodeling is tested. METHODS: Records of 30 subjects enrolled in a prospective clinical investigation of the inlay, implanted in emmetropic presbyopic subjects, were analyzed. The change to the anterior corneal surface was measured using wavefront techniques. The epithelial thinning profile was measured using Fourier domain optical coherence tomography. The stromal change was calculated from the two measurements. RESULTS: The inlay's volume displaced the stroma anterior to the inlay, which was reflected in the change of Bowman's layer shape. The epithelium anterior to the inlay thinned by 18.4 +/- 7.1 MUm. Peripheral to the inlay's diameter (2 mm), circumferential epithelial thickening extended the change to the anterior corneal surface to approximately twice the inlay diameter. The central anterior corneal surface rose by 9.8 +/- 3.4 MUm, creating a progressive add power profile. The epithelial thinning was linearly related to the curvature of the alteration to the anterior surface height, consistent with a theoretical model. CONCLUSIONS: When a meniscus-shaped corneal inlay is placed beneath a corneal flap, the flap's stroma takes on predominately the inlay's shape. The epithelium remodels within a zone approximately twice the inlay diameter, with an anterior corneal height change providing improved near and intermediate vision. The relationship between the epithelial, stromal, and anterior corneal surface changes confirms the hypothesis that epithelial changes are greatest in regions of greater local surface curvature. PMID- 27409468 TI - Comparison of Newer IOL Power Calculation Methods for Eyes With Previous Radial Keratotomy. AB - PURPOSE: To evaluate the accuracy of the optical coherence tomography-based (OCT formula) and Barrett True K (True K) intraocular lens (IOL) calculation formulas in eyes with previous radial keratotomy (RK). METHODS: In 95 eyes of 65 patients, using the actual refraction following cataract surgery as target refraction, the predicted IOL power for each method was calculated. The IOL prediction error (PE) was obtained by subtracting the predicted IOL power from the implanted IOL power. The arithmetic IOL PE and median refractive PE were calculated and compared. RESULTS: All formulas except the True K produced hyperopic IOL PEs at 1 month, which decreased at >=4 months (all P < 0.05). For the double-K Holladay 1, OCT formula, True K, and average of these three formulas (Average), the median absolute refractive PEs were, respectively, 0.78 diopters (D), 0.74 D, 0.60 D, and 0.59 D at 1 month; 0.69 D, 0.77 D, 0.77 D, and 0.61 D at 2 to 3 months; and 0.34 D, 0.65 D, 0.69 D, and 0.46 D at >=4 months. The Average produced significantly smaller refractive PE than did the double-K Holladay 1 at 1 month (P < 0.05). There were no significant differences in refractive PEs among formulas at 4 months. CONCLUSIONS: The OCT formula and True K were comparable to the double-K Holladay 1 method on the ASCRS (American Society of Cataract and Refractive Surgery) calculator. The Average IOL power on the ASCRS calculator may be considered when selecting the IOL power. Further improvements in the accuracy of IOL power calculation in RK eyes are desirable. PMID- 27409469 TI - Quantitative Evaluation of the Natural Progression of Keratoconus Using Three Dimensional Optical Coherence Tomography. AB - PURPOSE: We quantified the chronologic progression of keratoconus using anterior segment optical coherence tomography (AS-OCT). METHODS: A total of 217 eyes from 113 patients with keratoconus, keratoconus suspect, or forme fruste keratoconus were evaluated by corneal tomography using swept-source OCT. Age-dependent changes in the radius of the posterior best-fit sphere (Rpost), minimum corneal thickness (Tmin), and distance from the thinnest point to the corneal vertex (Dmin) were examined over follow-up periods of up to 5.79 years and were analyzed using generalized estimating equation (GEE) nonlinear regression model. RESULTS: Annual changes in Rpost (mean, -0.017 mm) and Tmin (-2.69 MUm) were significantly higher in younger patients (P < 0.01, GEE nonlinear regression) and in patients with higher maximal K value (Kmax; P < 0.01, GEE nonlinear regression), whereas no changes were observed in Dmin. Even in patients 30 years or older, 14% of eyes revealed remarkable progression in Rpost. In eyes with acute hydrops, annual changes in Rpost (-0.22 mm) and Tmin (-33.8 MUm) before acute corneal hydrops were more than 10 times faster than those in other eyes (P < 0.001, GEE nonlinear regression). CONCLUSIONS: Chronologic measurements of corneal tomography in keratoconus demonstrated that the progression of steepening at posterior corneal surface was found not only in patients under 30 years but also in older patients, particularly in advanced keratoconus. The rate of progression can be measured by mapping of corneal curvature and thickness using OCT, and the risk of progression was greater in younger patients with steeper Kmax. PMID- 27409470 TI - Corneal Epithelial Remodeling Induced by Small Incision Lenticule Extraction (SMILE). AB - PURPOSE: To assess the reactive changes of the corneal epithelial thickness (ET) profile induced by small incision lenticule extraction (SMILE) for treatment of myopia. METHODS: This prospective observational study included 46 eyes of 23 patients that were scheduled for myopic SMILE. High-resolution spectral-domain optical coherence tomography (SD-OCT) and a custom image segmentation algorithm were applied to measure corneal ET at multiple time points within the central 5 mm zone. Postoperative ET alterations were correlated with treatment parameters and refractive outcomes. RESULTS: Mean age was 33 +/- 6 years and mean spherical equivalent of surgical refractive correction was -4.78 +/- 1.75 diopters. The average ET (averaged over the central 5-mm zone) increased from 52.3 +/- 3.6 MUm preoperatively to 57.7 +/- 5.1 MUm 6 months postoperatively (P < 0.01). Average ET was 101.9% of the preoperative thickness at 24 hours postoperatively, 103.2% at 1 week, 106.7% at 6 weeks, 109.3% at 3 months, and 110.4% at 6 months postoperatively. The epithelial thickening response could be modeled by an exponential recovery function and stabilized after 3 months. The extent of epithelial hyperplasia was highly dependent on the magnitude of the induced refractive correction (P = 0.002). CONCLUSIONS: In this initial study of corneal ET remodeling after myopic SMILE, significant epithelial thickening was detected as a function of the extent of surgical refractive correction. Moreover, the epithelial remodeling response to the corneal refractive change appeared to decrease with higher age. In our hands, the observed epithelial changes did not appear to affect the refractive outcome of SMILE. (ClinicalTrials.gov number, NCT02614625). PMID- 27409471 TI - The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis. AB - PURPOSE: To determine the feasibility and accuracy of spectral-domain optical coherence tomography (SD-OCT) based grading of anterior chamber cell, using aqueous sampling as a standard, in a rabbit model of anterior uveitis. METHODS: Adult Dutch-belted rabbits were preimmunized with M. tuberculosis (Tb) H37RA antigen, 1 week prior to induction of anterior uveitis with an intracameral injection of Tb antigen. The anterior chamber was imaged with SD-OCT, followed by a slit lamp examination. Two independent, trained graders recorded their estimate of anterior chamber cell count using the Standardization of Uveitis Nomenclature (SUN) scores for each eye prior to performing an anterior chamber tap to determine the aqueous cell density using a hemocytometer. Using the aqueous cell density as a standard, correlation with SD-OCT counts were compared to those with SUN scores. RESULTS: Overall, SD-OCT correlated well with the hemocytometer counts (Spearman coefficient = 0.53, P < 0.001) compared with SUN grading and hemocytometer counts (Spearman coefficient = 0.02, P = 0.88). The correlation improved to 0.65 (P < 0.001) when we excluded eyes with corneal thickness >= 470 MUm. Eyes with corneal thickness >= 470 MUm exhibited the greatest degree of ocular inflammation and corneal opacity. CONCLUSIONS: In our rabbit model, SD-OCT grading of anterior chamber cell correlated significantly better with aqueous cell counts, compared to traditional slit lamp grading. Spectral-domain optical coherence tomography grading of anterior chamber cell may be a good alternative to SUN grading. Although SUN grading remains the clinical gold standard, alternative quantitative methods to assess ocular inflammation could provide insight into disease mechanism and aid in measuring treatment response. PMID- 27409472 TI - Effects of Valsalva Maneuver on Anterior Chamber Parameters and Choroidal Thickness in Healthy Chinese: An AS-OCT and SS-OCT Study. AB - PURPOSE: This study concurrently evaluated the effects of the Valsalva maneuver (VM) on the anterior and posterior ocular biometric parameters in a healthy Chinese cohort. METHODS: This prospective, cross-sectional study used anterior segment optical coherence tomography (AS-OCT) and swept-source optical coherence tomography (SS-OCT) to measure the anterior and posterior ocular biometric parameters before and during the VM. Sixty-three volunteers (126 eyes; 17 males and 46 females) were enrolled. The IOP, blood pressure (BP), and refractive error were recorded before and during a VM. RESULTS: The mean IOP showed a statistically significant increase (from 13.86-14.25 mm Hg, P = 0.005), but the different layers of the retina and the choroidal thickness (CT) showed no significant changes. The anterior chamber parameters decreased sharply from the baseline, with a smaller angle opening distance (AOD500; from 0.35-0.31 mm, P < 0.001), AOD750 (from 0.44-0.39 mm, P = 0.007), trabecular-iris space area (TISA500; from 0.14-0.13 mm, P = 0.027), TISA750 (from 0.25-0.23 mm, P = 0.007), and anterior chamber volume (ACV; from 143.09-139.84 mm3P = 0.036). Regression analyses revealed an association between DeltaIOP and the baseline IOP (beta = 0.26 [0.15, 0.37], P < 0.001) and DeltaACW (beta = -3.24 [-5.65, -0.83], P = 0.008). CONCLUSIONS: This study is the first to provide simultaneous evaluation of the effects of the VM on anterior and posterior ocular biometric parameters. The VM caused a significant IOP increase and narrowing of the angles in healthy subjects. However, it did not change the CT in the macular region. The relationship between IOP elevation and choroidal expansion during the VM needs further investigation. PMID- 27409473 TI - Posterior Eye Shape Measurement With Retinal OCT Compared to MRI. AB - PURPOSE: Posterior eye shape assessment by magnetic resonance imaging (MRI) is used to study myopia. We tested the hypothesis that optical coherence tomography (OCT), as an alternative, could measure posterior eye shape similarly to MRI. METHODS: Macular spectral-domain OCT and brain MRI images previously acquired as part of the Singapore Epidemiology of Eye Diseases study were analyzed. The right eye in the MRI and OCT images was automatically segmented. Optical coherence tomography segmentations were corrected for optical and display distortions requiring biometry data. The segmentations were fitted to spheres and ellipsoids to obtain the posterior eye radius of curvature (Rc) and asphericity (Qxz). The differences in Rc and Qxz measured by MRI and OCT were tested using paired t tests. Categorical assignments of prolateness or oblateness using Qxz were compared. RESULTS: Fifty-two subjects (67.8 +/- 5.6 years old) with spherical equivalent refraction from +0.50 to -5.38 were included. The mean paired difference between MRI and original OCT posterior eye Rc was 24.03 +/- 46.49 mm (P = 0.0005). For corrected OCT images, the difference in Rc decreased to -0.23 +/- 2.47 mm (P = 0.51). The difference between MRI and OCT asphericity, Qxz, was 0.052 +/- 0.343 (P = 0.28). However, categorical agreement was only moderate (kappa = 0.50). CONCLUSIONS: Distortion-corrected OCT measurements of Rc and Qxz were not statistically significantly different from MRI, although the moderate categorical agreement suggests that individual differences remained. This study provides evidence that with distortion correction, noninvasive office-based OCT could potentially be used instead of MRI for the study of posterior eye shape. PMID- 27409475 TI - Normative Data for Vascular Density in Superficial and Deep Capillary Plexuses of Healthy Adults Assessed by Optical Coherence Tomography Angiography. AB - PURPOSE: To establish a normative database for vascular density (VD) and foveal avascular zone (FAZ) at the superficial (SCP) and deep capillary plexus (DCP) in healthy subjects with optical coherence tomography (OCT) angiography. METHODS: The study was a retrospective chart review of healthy patients who had undergone OCT angiography imaging. A 3- * 3-mm area, centered on the fovea, was scanned for all the study eyes. The automated segmentation allowed separate analysis of the SCP, the DCP, and a comprehensive C-scan including both vascular layers. On the obtained images, VD and FAZ measurements were computed. Interobserver reproducibility and intraobserver repeatability were also assessed. RESULTS: A total of 135 eyes of 70 subjects (51% male) were analyzed. The mean age was 48.3 +/- 17.5. We divided patients into group 1, from 20 to 39 years of age; group 2, from 40 to 59 years; and group 3, age 60 years or older. At the level of the SCP, mean VD and mean FAZ +/- SD were, respectively, 52.58 +/- 3.22% and 0.28 +/- 0.1 mm2. At the level of the DCP, mean VD and mean FAZ were 57.87 +/- 2.82% and 0.37 +/- 0.12 mm2, respectively. The mean VD was significantly higher (P < 0.05) in DCP compared with SCP in all Early Treatment Diabetic Retinopathy Study (ETDRS) sectors and in all age groups. Vascular density was higher in women than in men after 60 years (P < 0.01). After adjustment on the signal strength index (SSI), the mean VD remained directly correlated with the age range and sex. The mean FAZ area was lower in group 3 (P < 0.05). Interobserver reproducibility was 0.78 to 0.99 in SCP and 0.67 to 0.92 in DCP, and intraobserver repeatability was 0.64 to 0.93 in SCP and 0.63 to 0.87 in DCP. CONCLUSIONS: Our study has provided, for the first time, age-related VD mapping data using OCT angiography in healthy subjects. The prototype software used in this study may help to improve the concept of VD grading with high inter- and intraexaminer repeatability and interexaminer reproducibility. PMID- 27409474 TI - Relationship Between Retinal Perfusion and Retinal Thickness in Healthy Subjects: An Optical Coherence Tomography Angiography Study. AB - PURPOSE: To investigate the relationship between retinal perfusion and retinal thickness in the peripapillary and macular areas of healthy subjects. METHODS: Using spectral-domain optic coherence tomography and split-spectrum amplitude decorrelation angiography (SSADA) algorithm, retinal perfusion and retinal thicknesses in the macular and peripapillary areas were measured in healthy volunteers, and correlations among these variables were analyzed. RESULTS: Overall, 64 subjects (121 eyes) including 28 males and 36 females with a mean +/- SD age of 38 +/- 13 years participated. Linear mixed-models showed that vessel area density was significantly correlated with the inner retinal thickness (from the inner limiting membrane to the outer border of the inner nucleus layer; P < 0.05), but not with the thickness of the full retina (P > 0.05) in the parafoveal area. The area of the foveal capillary-free zone was negatively correlated with the inner and full foveal thicknesses (all P < 0.001). In the peripapillary area, the vessel area density was positively correlated with the thickness of the retinal nerve fiber layer (P < 0.001). CONCLUSIONS: In healthy subjects, retinal perfusion in small vessels was closely correlated with the thickness of the inner retinal layers in both the macular and peripapillary areas. PMID- 27409476 TI - Optical Coherence Tomography Angiography Evaluation of the Parafoveal Vasculature and Its Relationship With Ocular Factors. AB - PURPOSE: To determine the size and characteristics of the superficial and deep foveal avascular zone (FAZ) in healthy adults by using optical coherence tomography angiography (OCT-A), and to ascertain the effects of demographic and ocular parameters on the FAZ size. METHODS: In a prospective cohort study of 117 healthy volunteers, foveal-centered 3 * 3-mm OCT-A scans were manually graded by certified graders to determine the size of the superficial and deep FAZ. Multiple linear regression analyses were performed to evaluate the impact of demographics and ocular factors, including central retinal thickness (CRT), choroidal thickness, axial length (AL), and spherical equivalent (SE) on superficial and deep FAZ areas. RESULTS: The mean age of the participants was 22.5 years, with mean AL of 25.4 mm and mean SE of -4.3 diopters. The mean CRT was 262.8 MUm (range, 220-316 MUm). The mean superficial FAZ area was 0.24 mm2, while the deep FAZ area was 0.38 mm2 (P < 0.001). Females had a larger superficial (P < 0.001) and deep FAZ (P < 0.001). On univariate linear regression, both superficial and deep FAZ areas had significant correlations with CRT, sex, AL, and SE, but not with age. By multiple linear regression analysis, in normal eyes, superficial FAZ area varied significantly with CRT and sex. Among eyes with high myopia, both superficial and deep FAZ varied significantly with CRT, sex, and choroidal thickness. CONCLUSIONS: The superficial and deep FAZ areas varied significantly among healthy eyes. Factors such as CRT, sex, SE, AL, and choroidal thickness influence the size of the FAZ. PMID- 27409477 TI - OCT-Based Macular Structure-Function Correlation in Dependence on Birth Weight and Gestational Age-the Giessen Long-Term ROP Study. AB - PURPOSE: To compare retinal layer thicknesses in preterm and term-born children using spectral-domain optical coherence tomography (SD-OCT) and to correlate structure with retinal function. METHODS: We performed SD-OCT single and volume scans in the foveal region of premature children aged 6 to 13 years without ROP (no-ROP, n = 100) and with spontaneously regressed ROP (sr-ROP, n = 50) documented with wide-angle digital imaging during routine screening for acute ROP, and 30 age-matched term-born children. Retinal layer segmentation and analysis was performed with custom-made software in single and volume-scans using an Early Treatment of Diabetic Retinopathy Study grid-based method, and compared to light increment sensitivity (LIS) data obtained with a microperimeter at eccentricity points of 0 degrees , 2.8 degrees , and 8 degrees , as previously described. RESULTS: Overall, seven children had to be excluded due to poor image quality (n = 1 no-ROP; n = 2 sr-ROP; n = 4 term). Total retina, ganglion cell + inner plexiform layer (GCL+) and outer nuclear layer + external limiting membrane (ONL+) thickness at the foveal center in no-ROP and sr-ROP were significantly higher compared with term children. Gestational age (GA) and birth weight (BW) were inversely correlated with these layer thicknesses. Rod and cone outer segment length did not differ in either group. The ratio of ONL+ to the whole retina at 0 degrees correlated significantly with reduced LIS. CONCLUSIONS: Increased thicknesses of the entire retina or specific layers at the fovea did not correlate with functional loss; but a thinner ONL in retinae without foveal pit did. This reduced ONL+ ratio is potentially caused by a reduced foveal cone density and may be the first morphologic functional correlate in prematurity and ROP. PMID- 27409478 TI - Optical Coherence Tomography Angiography in Central Retinal Vein Occlusion: Correlation Between the Foveal Avascular Zone and Visual Acuity. AB - PURPOSE: To investigate the relationship between best-corrected visual acuity (BCVA) and the foveal avascular zone (FAZ) in patients with central retinal vein occlusion (CRVO) evaluated with optical coherence angiography (OCT-A). METHODS: The study was a prospective consecutive case series including 24 patients with CRVO. All patients received either aflibercept or ranibizumab intravitreal injections prior to analysis. Best-corrected visual acuity and FAZ were evaluated in eyes without macular edema. The FAZ areas were evaluated with OCT-A in both the superficial and deep capillary plexus layers by using 3 * 3-mm images of the macula. Disruption of the ellipsoid zone (EZ) was also analyzed. RESULTS: The mean superficial FAZ area measured 0.76 mm2 (95% confidence interval [CI] 0.50 1.13). The mean deep FAZ area measured 1.12 mm2 (95% CI 0.77-1.47). In a multivariable analysis a negative correlation was found between the BCVA and the superficial FAZ area (r = -0.54, P = 0.03). The correlation between the BCVA and deep FAZ area did not meet statistical significance (r = -0.43, P = 0.09). In a multivariable analysis, disruption of the ellipsoid zone was significantly correlated to a larger superficial FAZ area (r = 0.68, P = <0.001) and poor visual acuity (r = 0.75, P < 0.001). CONCLUSIONS: Optical coherence tomography-A is a novel technique that allows segmented evaluation of the FAZ in patients with CRVO providing additional prognostic information. The FAZ areas were enlarged both in the superficial and the deep capillary networks. A significant correlation was found between BCVA and the FAZ area in CRVO patients without macular edema (ClinicalTrials.gov, number NCT02274259). PMID- 27409479 TI - En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease. AB - PURPOSE: We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). METHODS: We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. RESULTS: The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P < 0.001). Moreover, the longitudinal analysis, performed in 98 patients, showed a significant enlargement of macular lesion area at an estimated exponential rate of 4.6% per year (P = 0.046), together with a significant worsening of BCVA (0.06 logMAR per year; P < 0.001) and a significant decrease of macular thickness (1.6% per year; P = 0.005) over the follow-up. CONCLUSIONS: The current study describes, for the first time in literature, a longitudinal analysis of the macular lesion area assessed by SD-OCT in STGD1 disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials. PMID- 27409480 TI - Outer Retinal Changes Including the Ellipsoid Zone Band in Usher Syndrome 1B due to MYO7A Mutations. AB - PURPOSE: To study transition zones from normal to abnormal retina in Usher syndrome IB (USH1B) caused by myosin 7A (MYO7A) mutations. METHODS: Optical coherence tomography (OCT) scattering layers in outer retina were segmented in patients (n = 16, ages 2-42; eight patients had serial data, average interval 4.5 years) to quantify outer nuclear layer (ONL) and outer segments (OS) as well as the locus of EZ (ellipsoid zone) edge and its extent from the fovea. Static perimetry was measured under dark-adapted (DA) and light-adapted (LA) conditions. RESULTS: Ellipsoid zone edge in USH1B-MYO7A could be located up to 23 degrees from the fovea. Ellipsoid zone extent constricted at a rate of 0.51 degrees /year with slower rates at smaller eccentricities. A well-defined EZ line could be associated with normal or abnormal ONL and/or OS thickness; detectable ONL extended well beyond EZ edge. At the EZ edge, the local slope of LA sensitivity loss was 2.6 (+/-1.7) dB/deg for central transition zones. At greater eccentricities, the local slope of cone sensitivity loss was shallower (1.1 +/- 0.4 dB/deg for LA) than that of rod sensitivity loss (2.8 +/- 1.2 dB/deg for DA). CONCLUSIONS: In USH1B-MYO7A, constriction rate of EZ extent depends on the initial eccentricity of the transition. Ellipsoid zone edges in the macula correspond to large local changes in cone vision, but extramacular EZ edges show more pronounced losses on rod-based vision tests. It is advisable to use not only the EZ line but also other structural and functional parameters for estimating natural history of disease and possible therapeutic effects in future clinical trials of USH1B-MYO7A. PMID- 27409481 TI - Spectral-Domain Optical Coherence Tomography Findings in Neurofibromatosis Type 2. AB - PURPOSE: Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease, characterized by bilateral vestibular schwannomas, multiple central nervous system (CNS) tumors, skin tumors, and juvenile cataract. The present study assessed retinal abnormalities using spectral-domain optical coherence tomography (SD-OCT) in a case series of NF2 patients. METHODS: Nine NF2 patients from the neurofibromatosis outpatient reference center of the Federal University of Minas Gerais, in Brazil, were submitted to a complete anamnesis and a detailed ophthalmic evaluation, including SD-OCT, to detect retinal lesions. RESULTS: Of the nine NF2 patients evaluated, five had an early onset (<20 years) of NF2, and four patients had a late onset (>20 years) of symptoms. SD-OCT scans revealed retinal abnormalities in every patient with early onset (EOS) and in two patients with late onset (LOS) of the disease. In the EOS group, SD-OCT scans revealed flame-shaped epiretinal membranes (ERM) with peculiar characteristics in four eyes of three patients. Two patients had fine undulations of the inner retinal surface with a subtle ERM. Retinal hamartomas were present in four eyes of three patients with EOS; in two eyes, they were subclinical and were detected only by SD-OCT scans. In two patients with LOS and one patient with EOS, SD-OCT scans revealed retinal tufts of a nerve fiber layer. CONCLUSIONS: SD-OCT revealed ERM in most patients with NF2, therefore it may be a valuable exam for evaluating NF2 patients. Epiretinal membranes in NF2 has unique features, distinguishing it from idiopathic ERM or membranes associated with other diseases. We suggest that flame shaped ERM seems to be specific for NF2 and that ERM can be considered as an important diagnostic sign of NF2. PMID- 27409482 TI - Multimodal Imaging of Macular Telangiectasia Type 2: Focus on Vascular Changes Using Optical Coherence Tomography Angiography. AB - PURPOSE: To report morphologic features of idiopathic macular telangiectasia (MacTel) type 2 by means of optical coherence tomography angiography (OCTA) and to compare these findings to fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), confocal blue reflectance (CBR), and spectral-domain OCT (SD-OCT). In addition, foveal vessel density and parafoveal vascular density (PFVD), and foveal retinal thickness and parafoveal retinal thickness (PFRT) were compared between MacTel 2 patients and normal aged-matched controls. METHODS: Eight patients (15 eyes) with MacTel 2 and 17 normal controls (17 eyes) underwent retinal multimodal imaging assessment and grading. Results from different imaging techniques were used to compare interimaging modalities. Objective quantification of retinal vessel density and macular thickness was evaluated in MacTel 2 patients (15 eyes). RESULTS: In MacTel 2 eyes a comparison of OCTA to the other imaging techniques showed that the strongest correlations were present with SD OCT, early FFA, and late FFA. Moderate correlations were found between OCTA and CBR and FAF. Foveal vessel density was significantly lower in MacTel 2 eyes than control eyes both in the superficial plexus (23.74% vs. 33.14%; P = 0.003) and in the deep plexus (24.63% vs. 34.21%; P = 0.005). Superficial PFVD was significantly different in the two groups (47.06% vs. 51.40%; P = 0.005) but not the deep PFVD. Foveal retinal thickness was 214.13 MUm in MacTel 2 eyes and 258.18 MUm in normal controls, and PFRT was 279.60 and 323.29 MUm, respectively (P < 0.0001). CONCLUSIONS: Optical coherence tomography angiography is useful for retinal vasculature characterization in MacTel type 2 patients and showed a high correlation with well-established imaging techniques. PMID- 27409483 TI - Optical Coherence Tomography Angiography. AB - Optical coherence tomography angiography (OCTA) is a noninvasive approach that can visualize blood vessels down to the capillary level. With the advent of high speed OCT and efficient algorithms, practical OCTA of ocular circulation is now available to ophthalmologists. Clinical investigations that used OCTA have increased exponentially in the past few years. This review will cover the history of OCTA and survey its most important clinical applications. The salient problems in the interpretation and analysis of OCTA are described, and recent advances are highlighted. PMID- 27409484 TI - Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography. AB - PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) was used to characterize the retinal phenotype, natural history, and treatment responses in a mouse model of X-linked retinoschisis (Rs1-KO) and to identify new structural markers of AAV8-mediated gene therapy outcome. METHODS: Optical coherence tomography scans were performed on wild-type and Rs1-KO mouse retinas between 1 and 12 months of age and on Rs1-KO mice after intravitreal injection of AAV8 scRS/IRBPhRS (AAV8-RS1). Cavities and photoreceptor outer nuclear layer (ONL) thickness were measured, and outer retina reflective band (ORRB) morphology was examined with age and after AAV8-RS1 treatment. Outer retina reflective band morphology was compared to immunohistochemical staining of the outer limiting membrane (OLM) and photoreceptor inner segment (IS) mitochondria and to electron microscopy (EM) images of IS. RESULTS: Retinal cavity size in Rs1-KO mice increased between 1 and 4 months and decreased thereafter, while ONL thickness declined steadily, comparable to previous histologic studies. Wild-type retina had four ORRBs. In Rs1-KO, ORRB1was fragmented from 1 month, but was normal after 8 months; ORRB2 and ORRB3 were merged at all ages. Outer retina reflective band morphology returned to normal after AAV-RS1 therapy, paralleling the recovery of the OLM and IS mitochondria as indicated by anti-beta-catenin and anti-COX4 labeling, respectively, and EM. CONCLUSIONS: Spectral-domain OCT is a sensitive, noninvasive tool to monitor subtle changes in retinal morphology, disease progression, and effects of therapies in mouse models. The ORRBs may be useful to assess the outcome of gene therapy in the treatment of X-linked retinoschisis patients. PMID- 27409485 TI - Changes in Neovascular Lesion Hyperreflectivity After Anti-VEGF Treatment in Age Related Macular Degeneration: An Integrated Multimodal Imaging Analysis. AB - PURPOSE: To correlate presence of hyperreflective material (HRM) on spectral domain optical coherence tomography (SD-OCT) with color fundus photography (CFP) in patients with different subtypes of neovascular age-related macular degeneration (n-AMD). METHODS: Retrospective assessments were made at baseline and months 1, 3, and 12 after initiation of treatment. At baseline, CFP images were graded for the presence of blood, fibrin and lipid exudates, and retinal angiograms for n-AMD subtype. At the four selected visits, SD-OCT scans were graded for HRM type (well-defined or undefined) and location (subretinal, intraretinal, and subretinal pigment epithelium [RPE]), integrity of RPE, ellipsoid zone, and external limiting membrane (ELM). RESULTS: A total of 121 eyes with active n-AMD from 117 patients were included. At baseline, undefined HRM was strongly associated with fibrin on CFP (chi2 = 39.87; P < 0.001). The overall prevalence of HRM decreased from 85.9% at baseline to 52.9% by month 12. From baseline to month 12, undefined HRM decreased (53.7% vs. 7.4%, respectively) and well-defined HRM increased (32.2% vs. 45.5%, respectively). Sub-RPE HRM, which was infrequent at baseline, increased up to 30.6% by month 12. At month 12, eyes with no HRM had the best mean final best-corrected visual acuity (BCVA), and those with undefined HRM the worst. Multivariate regression analysis showed that ELM disruption at both baseline and month 12 was a negative predictive factor for final BCVA (P = 0.001 and P < 0.001, respectively), whereas presence of subretinal fluid at month 12 and number of treatments were positive predictors for final BCVA (P = 0.007 and P = 0.041, respectively), but the covariates describing HRM did not reach statistical significance in these models. CONCLUSIONS: In eyes with n-AMD, location and morphology of HRM changed after anti-VEGF treatment, and differences were observed in the various choroidal neovascularization (CNV) subtypes. After anti-VEGF treatment, it was well-defined HRM in the sub-RPE space that was observed mostly. PMID- 27409486 TI - Relationship Between Presumptive Inner Nuclear Layer Thickness and Geographic Atrophy Progression in Age-Related Macular Degeneration. AB - PURPOSE: To analyze inner retinal changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration and identify morphological cues for progression. METHODS: A total of 100 eyes with GA were assessed in this longitudinal, observational case series. Patients with GA and absent confounding pathology were compared with age-matched controls. The retinal layers on spectral domain optical coherence tomography, acquired in tracking mode, were segmented manually on central scans through the fixation point. Zones of GA were defined based on choroidal signal enhancement from retinal pigment epithelium loss. An area of unaffected temporal retina was used for comparison. Progression of GA was quantified with fundus autofluorescence. RESULTS: We analyzed 41 eyes of 41 patients (mean age 79.2 +/- 6.7 years). In areas of GA, the layer representing the inner nuclear layer (INL) in healthy retina was increased in thickness. Thickness of this presumptive INL was inversely correlated with best-corrected visual acuity (r = -0.48, P < 0.01). The presumptive INL thickness increase in atrophic areas was less marked in eyes with foveal sparing. Increased INL thickness in areas adjacent to GA was associated with a higher progression rate. CONCLUSIONS: Optical coherence tomography findings demonstrate that atrophy of the retinal pigment epithelium-photoreceptor complex in GA is associated with an increase of thickness of the presumptive INL, presumably caused by remodeling of the degenerating retina. Similar alterations in the retina adjacent to areas clinically affected by GA were associated with higher atrophy progression rates. PMID- 27409487 TI - Type 1 Choroidal Neovascularization Lesion Size: Indocyanine Green Angiography Versus Optical Coherence Tomography Angiography. AB - PURPOSE: To evaluate the size of type 1 choroidal neovascularization (CNV) in neovascular AMD by optical coherence tomography angiography (OCTA) and to compare with indocyanine green angiography (ICGA). METHODS: Patients diagnosed type 1 CNV underwent multimodal imaging by fluorescein angiography (FA), ICGA, spectral domain (SD)-OCT, and OCTA. Lesion size was measured both on OCTA at the choriocapillaris level with "select area" and "vessel area" functions, incorporated in AngioVue software and on ICGA at intermediate and late phases, by two masked independent readers. RESULTS: Nineteen eyes of 17 patients (mean age 80.6 +/- 8.36) were included in the analysis. Mean visual acuity was 0.2 logMAR. All OCTA revealed a high flow neovascular network in the choriocapillaris segmentation. On OCTA, interclass correlation between readers 1 and 2 was 0.96 (95% confidence interval [CI] 0.94-0.99) for select area and 0.97 (95% CI 0.96 0.99) for vessel area. The difference between lesion size in OCTA versus ICGA was detected in all eyes and it was statistically significant for both readers (P < 0.05). CONCLUSIONS: Optical coherence tomography angiography provides both quantitative and qualitative information on type 1 CNV and appears as a new reproducible way to evaluate CNV area and vessels area. Type 1 CNV lesion size in the choriocapillaris segmentation of OCTA and ICGA intermediate and late phases revealed that the OCTA size is significantly smaller than the ICGA size. This supports the idea that OCTA could be considered for evaluation of the neovascular lesion and for evaluation of therapeutic responses. PMID- 27409488 TI - A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization. AB - PURPOSE: To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. METHODS: Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. RESULTS: A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naive disease (P < 0.05, respectively). CONCLUSIONS: En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV. PMID- 27409489 TI - Characteristics of Polypoidal Choroidal Vasculopathy Evaluated by Optical Coherence Tomography Angiography. AB - PURPOSE: The purpose of this study was to compare the angiographic findings of polypoidal choroidal vasculopathy (PCV) detected by indocyanine green angiography (ICGA) and en face optical coherence tomography angiography (OCTA). METHODS: The study design was a retrospective chart review of 20 eyes with a clinical diagnosis of treatment-naive PCV, seen at Nagoya City University Hospital between December 2014 and January 2016. Indocyanine green angiography was performed with Heidelberg Retina Angiography 2 and OCTA was performed by using Avanti RTVue XR. RESULTS: Twenty eyes of 20 patients (18 male, 2 female) were studied. Average age was 71.9 years. Manual segmentation was required to detect the pathologic lesions of PCV in all cases. The polypoidal lesions were detected in 20 eyes (100%) by ICGA, and in 17 eyes (85%) by OCTA. The number of polypoidal lesions detected by OCTA averaged 2.6 +/- 1.9, with an average of 2.0 +/- 1.1 by ICGA (P < 0.05). The branching vascular network (BVN) was detected in 14 eyes (70%) by ICGA and in 14 eyes (70%) by OCTA. All of the BVNs detected by OCTA were located between the RPE and Bruch's membrane. CONCLUSIONS: Despite the manual segmentation required, en face OCTA enabled us to analyze the angiographic features of PCV combined with longitudinal image (B-scan). En face OCTA may be useful for understanding the pathogenesis of PCV and managing PCV. PMID- 27409490 TI - Imaging Laser-Induced Choroidal Neovascularization in the Rodent Retina Using Optical Coherence Tomography Angiography. AB - PURPOSE: The purpose of this study was to evaluate the performance of optical coherence tomography angiography (OCTA) in visualizing laser-induced choroidal neovascularization (CNV) in the rodent retina. METHODS: Choroidal neovascularization was induced via laser photocoagulation in 2 male Brown Norway rats and 2 male C57BL/6 mice. For qualitative comparison, the animals were imaged in vivo with OCTA, indocyanine green angiography (ICGA), and fluorescein angiography (FA), and ex vivo with immunofluorescence confocal microscopy, 14 days post laser photocoagulation without anti-vascular endothelial growth factor (anti-VEGF) intervention. For longitudinal quantitative analysis, CNV was induced in 6 additional male C57BL/6 mice. Three mice intravitreally received an anti VEGF agent and the remaining 3 mice phosphate buffered saline (PBS) vehicle 7 days post laser photocoagulation. These animals were imaged using OCTA 6, 14, and 21 days post laser photocoagulation. The area and volume of the laser-induced CNV lesions were measured longitudinally. RESULTS: In both mice and rats, OCTA qualitatively showed high correlation with FA, ICGA, and immunofluorescence imaging. Unlike FA and ICGA, which does not show the microvasculature due to dye leakage, OCTA visualized the CNV microvasculature with resolution and contrast comparable to immunofluorescence images. Longitudinal imaging enabled normalization of the CNV area and volume, reducing inherent variation in the CNV size. By using only 3 mice in each group, statistically significant differences (P < 0.01) in the CNV area and volume could be demonstrated. CONCLUSIONS: Optical coherence tomography angiography enables noninvasive visualization of the laser induced CNV microvasculature in the rodent retina with high resolution and tissue lumen contrast, providing quantifiable in vivo measurements for longitudinal analysis. PMID- 27409492 TI - New Insights Into Microaneurysms in the Deep Capillary Plexus Detected by Optical Coherence Tomography Angiography in Diabetic Macular Edema. AB - PURPOSE: To study the association between the distributions of microaneurysms detected by en face optical coherence tomography angiography (OCTA) and diabetic macular edema (DME). METHODS: The study design was a retrospective chart review of 27 patients (33 eyes) with DME. The eyes were scanned using OCTA (6 * 6 mm) and spectral-domain (SD) OCT macular cube. Each of the images of the capillary plexus was overlaid onto the image of the topographic map, and the densities of the microaneurysms were measured by ImageJ software. The association between the distribution of microaneurysms and macular edema was evaluated. RESULTS: For microaneurysms in areas with and without edema, 77.3 +/- 8.1% of these microaneurysms were located in the deep capillary plexuses (DCP). However, in areas of edema where the retinal thickness was more than 400 MUm, 91.3 +/- 9.1% of the microaneurysms were found in the DCP. This difference was statistically significant (P < 0.001). In the macular edema area, there was a significantly higher density of microaneurysms in the DCP compared to the superficial capillary plexuses (1.71/mm2 vs. 0.17/mm2, P < 0.001). There was also a significant correlation between the macular volume and the density of microaneurysms in the DCP in edema (r = 0.63, P < 0.001). CONCLUSIONS: Our study demonstrated a high proportion of microaneurysms in the DCP, as well as a novel association between the distributions of microaneurysms detected by OCTA and DME. Results also indicated that microaneurysms located in the DCP contribute to the pathogenesis of DME. PMID- 27409491 TI - Alterations in Retinal Layer Thickness and Reflectance at Different Stages of Diabetic Retinopathy by En Face Optical Coherence Tomography. AB - PURPOSE: This article reports a method for en face optical coherence tomography (OCT) imaging and quantitative assessment of alterations in both thickness and reflectance of individual retinal layers at different stages of diabetic retinopathy (DR). METHODS: High-density OCT raster volume scans were acquired in 29 diabetic subjects divided into no DR (NDR) or non-proliferative DR (NPDR) groups and 22 control subjects (CNTL). A customized image segmentation method identified eight retinal layer interfaces and generated en face thickness maps and reflectance images for nerve fiber layer (NFL), ganglion cell and inner plexiform layers (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE). Mean thickness and intensity values were calculated in nine macular subfields for each retinal layer. RESULTS: En face thickness maps and reflectance images of retinal layers in CNTL subjects corresponded to normal retinal anatomy. Total retinal thickness correlated negatively with age in nasal subfields (R <=-0.31; P <= 0.03, N = 51). In NDR subjects, NFL and OPL thickness were decreased (P = 0.05), and ONL thickness was increased (P = 0.04) compared to CNTL. In NPDR subjects, GCLIPL thickness was increased in perifoveal subfields (P< 0.05) and INL intensity was higher in all macular subfields (P = 0.04) compared to CNTL. CONCLUSIONS: Depth and spatially resolved retinal thickness and reflectance measurements are potential biomarkers for assessment and monitoring of DR. PMID- 27409493 TI - Visualization of Changes in the Choriocapillaris, Choroidal Vessels, and Retinal Morphology After Focal Laser Photocoagulation Using OCT Angiography. AB - PURPOSE: To utilize optical coherence tomography (OCT) and OCT angiography (OCTA) to describe alterations in the retinal and choriocapillaris vasculature following remote laser photocoagulation. Lesions are classified on the basis of choriocapillaris alteration as evaluated on en face OCTA. METHODS: This was a retrospective, cross-sectional study analyzing 28 laser photocoagulation scars from 8 patients treated for diabetic macular edema. All eyes were analyzed using a combination of OCTA, en face and cross-sectional OCT, and fundus photography. Two masked readers scored images for alterations at the level of the retinal pigment epithelium (RPE), choroid, and choriocapillaris. Laser photocoagulation lesions were classified as deep if choriocapillaris alteration was present on OCTA; lesions were classified as superficial if no choriocapillaris alteration was present on OCTA. RESULTS: Optical coherence tomography angiography was found to be useful for evaluation of choriocapillaris alteration underlying regions of laser scarring. Of the 28 analyzed laser scars, 13 were classified as superficial and 15 were classified as deep. CONCLUSIONS: Optical coherence tomography angiography can be used to visualize choriocapillaris alterations associated with focal laser photocoagulation treatment. PMID- 27409494 TI - Quantifying Microvascular Density and Morphology in Diabetic Retinopathy Using Spectral-Domain Optical Coherence Tomography Angiography. AB - PURPOSE: To quantify changes in retinal microvasculature in diabetic retinopathy (DR) by using spectral-domain optical coherence tomography angiography (SD-OCTA). METHODS: Retrospective, cross-sectional, observational study of healthy and diabetic adult subjects with and without DR. Retinal microvascular changes were assessed by using SD-OCTA images and an intensity-based optical microangiography algorithm. A semiautomated program was used to calculate indices of microvascular density and morphology in nonsegmented and segmented SD-OCTA images. Microvascular density was quantified by using skeleton density (SD) and vessel density (VD), while vessel morphology was quantified as fractal dimension (FD) and vessel diameter index (VDI). Statistical analyses were performed by using the Student's t-test or analysis of variance with post hoc Tukey honest significant difference tests for multiple comparisons. RESULTS: Eighty-four eyes with DR and 14 healthy eyes were studied. Spearman's rank test demonstrated a negative correlation between DR severity and SD, VD, and FD, and a positive correlation with VDI (rho = -0.767, -0.7166, -0.768, and +0.5051, respectively; P < 0.0001). All parameters showed high reproducibility between graders (ICC = 0.971, 0.962, 0.937, and 0.994 for SD, VD, FD, and VDI, respectively). Repeatability (kappa) was greater than 0.99 for SD, VD, FD, and VDI. CONCLUSIONS: Vascular changes in DR can be objectively and reliably characterized with SD, VD, FD, and VDI. In general, decreasing capillary density (SD and VD), branching complexity (FD), and increasing average vascular caliber (VDI) were associated with worsening DR. Changes in capillary density and morphology were significantly correlated with diabetic macular edema. PMID- 27409496 TI - Enhanced-Depth Imaging Optical Coherence Tomography of the Human Choroid In Vivo Compared With Histology After Enucleation. AB - PURPOSE: This study compared in vivo enhanced-depth imaging optical coherence tomography (EDI-OCT) with ex vivo histology of the choroid in human eyes. METHODS: Three eyes in three patients with advanced iris melanoma without posterior segment involvement underwent EDI-OCT less than 24 hours prior to enucleation and, in one eye, immediately after enucleation. Following fixation in 4% buffered formaldehyde and paraffin embedding, serial sections of the whole eye were cut horizontally, mounted, stained with hematoxylin-eosin and digitized. Alignment between histology and EDI-OCT was made on landmarks such as retinal vessel, the foveal depression, ciliary arteries, drusen, and nevi. RESULTS: Intra and interindividual variations in relative choroidal thickness were comparable between the two modalities. After histologic fixation of the three melanoma eyes, the fullness of the choroidal vessels was reduced and subfoveal choroid thickness reduced to 56%, 45%, and 56%, respectively, of its in vivo thickness on EDI-OCT. CONCLUSIONS: There were no identifiable discrepancies in choroidal structural patterns between clinical EDI-OCT and histologic sections except that after enucleation and histologic fixation choroidal thickness was reduced to roughly half of its in vivo value, a phenomenon that may reflect the high content of blood vessels in the choroid. PMID- 27409497 TI - Visual Function and Central Retinal Structure in Choroideremia. AB - PURPOSE: To define the clinical phenotype of a cohort of patients affected with choroideremia. METHODS: A retrospective study of patients with choroideremia included two centers. Data collected included age, visual acuity, refractive error, color vision, kinetic perimetry, optical coherence tomography (OCT), and genotype information. RESULTS: Sixty male participants were recruited. Genotype information was available for 58 cases, and nonsense mutations were most commonly observed. Eight novel mutations were identified including a missense mutation. The mean age at the first visit was 30.1 years (range, 5-65 years) and thirty seven patients (61%) had more than one visit with a mean follow-up period of 10.3 years (range, 1-23 years). Visual acuity was not associated with age for patients younger than 30 years (P = 0.46) but significantly associated with age for the age group above 30 years (P < 0.0001). Central retinal thickness was significantly associated with visual acuity (P = 0.03) and with age (P = 0.0014). The extent of visual field documented by kinetic perimetry showed a negative correlation with age to tested stimuli; the smallest target used (I-4e) showed the earliest and most rapid deterioration below the age of 20 years (P = 0.0032). Color vision was abnormal in 46.7% of cases (mean age, 36.3 years; range, 18-61 years), which was associated with older age (P = 0.0039). Central OCT images were abnormal in all cases, as early as age 10 years. Outer retinal tubulations were observed in all but five patients. No genotype-phenotype correlation was observed. CONCLUSIONS: This comprehensive structural and functional characterization of a large cohort of patients with molecularly confirmed choroideremia indicates that certain parameters are not changing significantly with time while others are. The latter warrants a prospective natural history study, ultimately to be considered as outcome measures for interventional clinical trials. PMID- 27409495 TI - Optical Coherence Tomography for Retinal Surgery: Perioperative Analysis to Real Time Four-Dimensional Image-Guided Surgery. AB - Magnification of the surgical field using the operating microscope facilitated profound innovations in retinal surgery in the 1970s, such as pars plana vitrectomy. Although surgical instrumentation and illumination techniques are continually developing, the operating microscope for vitreoretinal procedures has remained essentially unchanged and currently limits the surgeon's depth perception and assessment of subtle microanatomy. Optical coherence tomography (OCT) has revolutionized clinical management of retinal pathology, and its introduction into the operating suite may have a similar impact on surgical visualization and treatment. In this article, we review the evolution of OCT for retinal surgery, from perioperative analysis to live volumetric (four dimensional, 4D) image-guided surgery. We begin by briefly addressing the benefits and limitations of the operating microscope, the progression of OCT technology, and OCT applications in clinical/perioperative retinal imaging. Next, we review intraoperative OCT (iOCT) applications using handheld probes during surgical pauses, two-dimensional (2D) microscope-integrated OCT (MIOCT) of live surgery, and volumetric MIOCT of live surgery. The iOCT discussion focuses on technological advancements, applications during human retinal surgery, translational difficulties and limitations, and future directions. PMID- 27409498 TI - In Vivo Detection of Laminar and Peripapillary Scleral Hypercompliance in Early Monkey Experimental Glaucoma. AB - PURPOSE: To compare optical coherence tomography (OCT) detected, optic nerve head (ONH) compliance within control and experimental glaucoma (EG) eyes of 15 monkeys at EG onset. METHODS: Intraocular pressure (IOP) was chronically elevated in one eye of each animal using a laser. Experimental glaucoma onset was identified using confocal scanning laser tomography (CSLT). Optical coherence tomography ONH imaging (40 radial B-scans) was performed at 10 mm Hg before and after laser. At EG onset, OCT scans were obtained at IOP 10 and 30 mm Hg. Optical coherence tomography landmarks within the IOP 10/30 images were delineated to quantify IOP 10/30 differences (compliance) for anterior lamina cribrosa surface depth (ALCSD) relative to Bruch's membrane opening (BMO) (ALCSD-BMO), ALCSD relative to peripheral BM (ALCSD-BM), and BMO depth relative to peripheral BM (BMOD-BM). A linear mixed effects model assessed for acute IOP elevation effects, control versus EG eye effects, and their interaction. RESULTS: Effects of IOP elevation were greater in EG versus control eyes for ALCSD-BMO (-46 +/- 45 vs. -8 +/- 13 MUm, P = 0.0042) and ALCSD-BM (-92 +/- 64 vs. -42 +/- 22 MUm, P = 0.0075). Experimental glaucoma eye-specific ALCSD-BMO and ALCSD-BM compliance exceeded the range of control eye compliance in 9 and 8 of the 15 EG eyes, respectively. Post laser peak IOP (R2 = 0.798, P < 0.0001) and post-laser mean IOP (R2 = 0.634, P < 0.0004) most strongly correlated to EG versus control eye differences in ALCSD BMO compliance. CONCLUSIONS: Laminar (ALCSD-BMO) and peripapillary scleral (ALCSD BM) hypercompliance are present in most monkey eyes at the onset of EG. PMID- 27409499 TI - Comparing Optic Nerve Head Rim Width, Rim Area, and Peripapillary Retinal Nerve Fiber Layer Thickness to Axon Count in Experimental Glaucoma. AB - PURPOSE: We compare spectral-domain optical coherence tomography (SDOCT) measurements of minimum rim width (MRW), minimum rim area (MRA), and peripapillary retinal nerve fiber layer thickness (RNFLT) to complete orbital optic nerve axon counts in nonhuman primates (NHP) with unilateral experimental glaucoma (EG). METHODS: Biweekly SDOCT measurements of MRW, MRA, and RNFLT were acquired under manometric IOP control (10 mm Hg) in 51 NHP during baseline (mean +/- SD, 5.0 +/- 1.6 sessions) and after laser photocoagulation was applied to the trabecular meshwork of one eye to induce chronic IOP elevation. At the study endpoint (predefined for each NHP), 100% axon counts were obtained from each optic nerve. RESULTS: For SDOCT parameters at baseline, the correlation between the two eyes of each animal was strongest for RNFLT (R = 0.97) and MRW (R = 0.97), but lower for MRA (R = 0.85). At the final time point, average values in EG eyes relative to control eyes were: -22% for RNFLT, -38% for MRW, -36% for MRA, and -36% for optic nerve axons. The correlation with axon counts was strongest for RNFLT (R = 0.81), compared to MRW (R = 0.72, P = 0.001) or MRA (R = 0.70, P = 0.001). Diagnostic sensitivity was 75% for RNFLT, 90% for MRW, and 88% for MRA; all had 100% specificity. CONCLUSIONS: Peripapillary RNFLT was correlated more closely with total orbital optic nerve axon count than were the ONH parameters MRW or MRA. This is likely because glaucomatous deformation (beyond axon loss alone) has a greater influence on the ONH parameters MRW and MRA than on RNFLT. PMID- 27409500 TI - Optic Nerve Head Measurements With Optical Coherence Tomography: A Phantom-Based Study Reveals Differences Among Clinical Devices. AB - PURPOSE: Optical coherence tomography (OCT) can monitor for glaucoma by measuring dimensions of the optic nerve head (ONH) cup and disc. Multiple clinical studies have shown that different OCT devices yield different estimates of retinal dimensions. We developed phantoms mimicking ONH morphology as a new way to compare ONH measurements from different clinical OCT devices. METHODS: Three phantoms were fabricated to model the ONH: One normal and two with glaucomatous anatomies. Phantoms were scanned with Stratus, RTVue, and Cirrus clinical devices, and with a laboratory OCT system as a reference. We analyzed device reported ONH measurements of cup-to-disc ratio (CDR) and cup volume and compared them with offline measurements done manually and with a custom software algorithm, respectively. RESULTS: The mean absolute difference between clinical devices with device-reported measurements versus offline measurements was 0.082 vs. 0.013 for CDR and 0.044 mm3 vs. 0.019 mm3 for cup volume. Statistically significant differences between devices were present for 16 of 18 comparisons of device-reported measurements from the phantoms. Offline Cirrus measurements tended to be significantly different from those from Stratus and RTVue. CONCLUSIONS: The interdevice differences in CDR and cup volume are primarily caused by the devices' proprietary ONH analysis algorithms. The three devices yield more similar ONH measurements when a consistent offline analysis technique is applied. Scan pattern on the ONH also may be a factor in the measurement differences. This phantom-based study has provided unique insights into characteristics of OCT measurements of the ONH. PMID- 27409501 TI - The Relative Odds of Progressing by Structural and Functional Tests in Glaucoma. AB - PURPOSE: The purpose of this study was to evaluate the effect of disease severity and number of tests acquired during follow-up on the relative odds of identifying progression by structural or functional tests in glaucoma. METHODS: This was an observational cohort study involving 462 eyes of 305 patients with glaucoma and 62 eyes of 49 healthy subjects. Glaucoma patients and healthy subjects were followed for an average of 3.6 +/- 0.9 and 3.8 +/- 0.9 years, with a median (interquantile range) of 8 (6-9) and 7 (6-8) visits, respectively. At each visit, subjects underwent visual field assessment with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) evaluation by spectral-domain optical coherence tomography (SD-OCT). Slopes of change in SAP mean sensitivity and OCT RNFL thickness over time were estimated by linear regression using progressively cumulative visits over time. Cutoff values for age-related expected rates of change for each test were obtained from the healthy group. Progression by SD-OCT and/or SAP was determined if the slope of change was statistically significant and also lower (faster) than the fifth percentile cutoff calculated from the healthy group. A generalized estimating equation logistic regression model was used to evaluate the relative odds of progressing by OCT versus SAP in glaucoma eyes. RESULTS: Eyes with less severe disease at baseline had a higher chance of being detected as progressing by SD-OCT but not by SAP, whereas an increase in disease severity at baseline increased the chance that the eye would be detected as progressing by SAP but not SD-OCT. Each 1 dB higher MD was associated with a 5% increase in the odds of detecting progression by SD-OCT versus SAP (odds ratio = 1.05 per 1 dB; 95% confidence interval: 1.01-1.09; P = 0.005). CONCLUSIONS: The ability to detect glaucoma progression by SAP versus SD-OCT is significantly influenced by the stage of disease. Our results may provide useful information for guiding clinicians on the relative utility of these tests for detecting change throughout the disease continuum. PMID- 27409502 TI - The Pattern of Visual Fixation Eccentricity and Instability in Optic Neuropathy and Its Spatial Relationship to Retinal Ganglion Cell Layer Thickness. AB - PURPOSE: The purpose of this study was to assess whether clinically useful measures of fixation instability and eccentricity can be derived from retinal tracking data obtained during optical coherence tomography (OCT) in patients with optic neuropathy (ON) and to develop a method for relating fixation to the retinal ganglion cell complex (GCC) thickness. METHODS: Twenty-nine patients with ON underwent macular volume OCT with 30 seconds of confocal scanning laser ophthalmoscope (cSLO)-based eye tracking during fixation. Kernel density estimation quantified fixation instability and fixation eccentricity from the distribution of fixation points on the retina. Preferred ganglion cell layer loci (PGCL) and their relationship to the GCC thickness map were derived, accounting for radial displacement of retinal ganglion cell soma from their corresponding cones. RESULTS: Fixation instability was increased in ON eyes (0.21 deg2) compared with normal eyes (0.06982 deg2; P < 0.001), and fixation eccentricity was increased in ON eyes (0.48 degrees ) compared with normal eyes (0.24 degrees ; P = 0.03). Fixation instability and eccentricity each correlated moderately with logMAR acuity and were highly predictive of central visual field loss. Twenty-six of 35 ON eyes had PGCL skewed toward local maxima of the GCC thickness map. Patients with bilateral dense central scotomas had PGCL in homonymous retinal locations with respect to the fovea. CONCLUSIONS: Fixation instability and eccentricity measures obtained during cSLO-OCT assess the function of perifoveal retinal elements and predict central visual field loss in patients with ON. A model relating fixation to the GCC thickness map offers a method to assess the structure-function relationship between fixation and areas of preserved GCC in patients with ON. PMID- 27409503 TI - Glaucoma Increases Retinal Surface Contour Variability as Measured by Optical Coherence Tomography. AB - PURPOSE: We investigated the feasibility of glaucoma detection by measuring retinal surface contour variability (RSCV) using optical coherence tomography (OCT). METHODS: The peripapillary region in one eye of each participant was scanned over an 8 * 8 mm area with a swept source OCT prototype. The retinal surface contour was sampled at approximately 1.5- to 3.5-mm radius circles centered on the optic nerve head. The RSCV is defined as the average log value within a middle spatial frequency band of the Fourier transform to the elevation profile of the inner retinal surface. The spatial frequency band was optimized to distinguish glaucoma from normal. Nerve fiber layer thickness (NFLT) was sampled around a 1.7-mm radius circle. Glaucoma severity was assessed by automated static perimetry. RESULTS: We enrolled 17 glaucomatous eyes and 17 healthy eyes. A great majority of the glaucoma group were in the early stage (visual field mean deviation average -2.48 +/- 3.73 dB). Significant differences were found for RSCV between glaucoma and control eyes (P < 0.003) at all radii. The area under the receiver operating characteristic curve (AROC = 0.90) of RSCV was best at the 3.5 mm radius. This was not significantly better than NFLT (AROC = 0.84). With the 99% specificity, the glaucoma detection sensitivity was 53% for RSCV and 29% for NFLT (P = 0.13). CONCLUSIONS: Retinal surface contour variability was significantly increased in glaucoma patients. The diagnostic accuracy of RSCV was equal to NFLT in early glaucoma. Since the RSCV detects small-scale focal damage and the average NFLT measures global damage, they provide different diagnostic information that may be synergistic. PMID- 27409504 TI - Correlation Between En Face Optical Coherence Tomography Defects of the Inner Retinal Layers and Ganglion Cell Inner Plexiform Layer Analysis After Internal Limiting Membrane Peeling for Idiopathic Full-Thickness Macular Hole. AB - PURPOSE: The purpose of this study was to report en face optical coherence tomography (OCT) inner retinal changes after internal limiting membrane (ILM) peeling for idiopathic full-thickness macular hole (IFTMH) and to correlate these findings with macular ganglion cell inner plexiform layer (GC-IPL) analysis. METHODS: This prospective study included 20 patients with IFTMH treated using pars plana vitrectomy with ILM peeling. All patients were analyzed using en face OCT at 6 months after surgery to determinate the effect of ILM peeling on the inner retinal layers. Correlation between the GC-IPL en face OCT findings and that obtained by three-dimensional volumetric OCT scanning also was performed. RESULTS: Seven patients (35%) showed defects in the retinal nerve fiber layer (RNFL) that appeared as multiple dark dots with no visible defects at the GC-IPL, either with en face OCT or 3D volumetric OCT scanning. Thirteen patients (65%) showed a similar combination of RNFL defects and well-circumscribed defects in the underlying GC-IPL. These defects could be visualized on en face OCT display, and they correlated with areas of GC-IPL thinning detected in the 3D volumetric OCT scanning. CONCLUSIONS: With ILM peeling, en face OCT scanning showed two forms of inner retinal layers changes. The first form was the concentric macular dark spots (CMDS) with intact GC-IPL. The second form appeared in the CMDS with evident localized defects in the underlying GC-IPL. These defects correlate with the areas of GC-IPL thinning detected using 3D volumetric OCT scanning. PMID- 27409506 TI - Key Developments for Partial Coherence Biometry and Optical Coherence Tomography in the Human Eye Made in Vienna. AB - PURPOSE: To describe key developments of optical biometry and optical coherence tomography (OCT) for ophthalmic applications made by one of the pioneering research groups. METHODS: Partial coherence interferometry (PCI) as the basic ranging technology for modern optical biometry and for OCT was introduced for biomedical applications in the 1980s. Later, Fourier domain (FD) OCT was introduced and demonstrated to provide superior sensitivity as compared to time domain OCT. Further developments comprised ultrahigh-resolution OCT and deep penetration OCT at wavelengths of approximately 1050 nm. Important functional extensions comprise Doppler OCT/OCT angiography, polarization-sensitive OCT, and adaptive optics OCT. RESULTS: High-precision PCI biometry has found extensive applications in cataract surgery and in research on intraocular lens design. Optical coherence tomography, especially in the second-generation variant of FD OCT, is now indispensable for ocular diagnostics in general and for retinal diagnostics in particular; 1050 nm OCT shows improved penetration into deeper layers like the choroid. CONCLUSIONS: The contributions of the Vienna research group helped to establish PCI biometry and FD OCT as the gold standards in their respective fields. PMID- 27409505 TI - Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes. AB - PURPOSE: The purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients. METHODS: Two hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-MUm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy. RESULTS: Age-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 +/- 7%, 60.3 +/- 5%, and 64.2 +/- 3%, respectively; P < 0.001; and wiVD: 46.2 +/- 6%, 51.3 +/- 5%, and 56.6 +/- 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65). CONCLUSIONS: Optical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT A measurements reflect damage to tissues relevant to the pathophysiology of OAG. PMID- 27409508 TI - Pediatric Optical Coherence Tomography in Clinical Practice-Recent Progress. AB - PURPOSE: Optical coherence tomography (OCT) has revolutionized the diagnosis and management of adult retinal and optic nerve disease. Children were deprived of this technology until the recent development of handheld spectral-domain OCT (HH SDOCT). In this article, we review the applications of OCT imaging in pediatric ophthalmology. METHODS: This study was a review of the literature. RESULTS: The acquisition and interpretation of pediatric tomograms differ significantly from those for adults, with adjustments needed to account for the shorter axial lengths, higher refractive errors, and ongoing retinal and optic nerve development in the pediatric eye. Handheld SDOCT is increasingly being used as an adjunctive diagnostic tool in retinopathy of prematurity (ROP) and nonaccidental injury (NAI) by providing additional morphologic information that is not normally clinically discernible. The role of HH-SDOCT in streamlining diagnosis in infantile nystagmus syndrome, retinal dystrophies, and degenerations has been established. Optical coherence tomography can also help differentiate between pediatric intraocular tumors, for example, hamartomas and retinoblastoma; monitor tumor progression; and monitor treatment response. In addition, HH-SDOCT is establishing its role as a noninvasive monitoring tool in children affected by optic nerve pathology such as glaucoma, optic nerve atrophy and hypoplasia, optic pathway glioma, and pseudotumor cerebri. CONCLUSIONS: Handheld SDOCT can provide novel insights into the natural history of retinal and optic nerve diseases in young children. For example, in achromatopsia and albinism, in vivo OCT studies have provided evidence of altered but ongoing retinal development in early childhood, which suggests that potentially targeting treatment at an earlier age may optimize visual function by normalizing retinal development. PMID- 27409509 TI - Technology and the Glaucoma Suspect. AB - PURPOSE: To determine and compare the diagnostic performance of spectral-domain optical coherence tomography (SD-OCT), stereoscopic disc photographs, and automated perimetry as assessed by a group of glaucoma specialists in differentiating individuals with early glaucoma from suspects. METHODS: Forty-six eyes (46 patients) with suspicious optic nerves had previously undergone SD-OCT scans, 24-2 visual fields (VFs), and optic disc photographs. The average VF mean deviation was -1.97 +/- 2.09 (SD) dB. Four glaucoma specialists examined the 138 individual diagnostic tests and classified the patient as likely glaucomatous or nonglaucomatous based on the results of a single test. The diagnostic performances of each of the three tests were compared to a previously determined reference standard, based on the consensus of a separate panel of four glaucoma specialists who examined all three tests together. RESULTS: Among the four specialists, the interobserver agreement across the three diagnostic tests was poor for VF and photos, with kappa (kappa) values of 0.13 and 0.16, respectively, and moderate for OCT, with kappa value of 0.40. Using panel consensus as reference standard, OCT had the highest discriminative ability, with an area under the curve (AUC) of 0.99 (95% 0.96-1.0) compared to photograph AUC 0.85 (95% 0.73-0.96) and VF AUC 0.86 (95% 0.76-0.96), suggestive of closer performance to that of a group of glaucoma specialists. CONCLUSIONS: Compared to VF and disc photography, SD-OCT, when used alone, had better internal agreement as well as better agreement with the consensus of clinicians using all available data. Future studies should evaluate best practices for SD-OCT interpretation. PMID- 27409507 TI - A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future. AB - PURPOSE: Optical coherence tomography (OCT) has enabled "virtual biopsy" of the living human retina, revolutionizing both basic retina research and clinical practice over the past 25 years. For most of those years, in parallel, adaptive optics (AO) has been used to improve the transverse resolution of ophthalmoscopes to foster in vivo study of the retina at the microscopic level. Here, we review work done over the last 15 years to combine the microscopic transverse resolution of AO with the microscopic axial resolution of OCT, building AO-OCT systems with the highest three-dimensional resolution of any existing retinal imaging modality. METHODS: We surveyed the literature to identify the most influential antecedent work, important milestones in the development of AO-OCT technology, its applications that have yielded new knowledge, research areas into which it may productively expand, and nascent applications that have the potential to grow. RESULTS: Initial efforts focused on demonstrating three-dimensional resolution. Since then, many improvements have been made in resolution and speed, as well as other enhancements of acquisition and postprocessing techniques. Progress on these fronts has produced numerous discoveries about the anatomy, function, and optical properties of the retina. CONCLUSIONS: Adaptive optics OCT continues to evolve technically and to contribute to our basic and clinical knowledge of the retina. Due to its capacity to reveal cellular and microscopic detail invisible to clinical OCT systems, it is an ideal companion to those instruments and has the demonstrable potential to produce images that can guide the interpretation of clinical findings. PMID- 27409511 TI - Appearance of the Retina With Full-Field Optical Coherence Tomography. AB - PURPOSE: To interpret full-field optical coherence tomography (FFOCT) images of ex vivo retina. METHODS: Flatmounted retinas of human, primate, pig, sheep, rat, and mouse were imaged using FFOCT. To identify retinal ganglion and amacrine cells, fixed samples immunolabeled against Tuj1 and Brn3a or live samples labeled in vitro with green fluorescent protein (GFP) were analyzed by combining FFOCT, fluorescence confocal microscopy (FCM), and fluorescence-FFOCT. To investigate postmortem tissue changes, time series were acquired over 48 hours and on fresh versus fixed tissue. RESULTS: With FFOCT, cell types and features such as nerve fiber bundles and RGC somas were resolved without use of contrast agents at 1-MUm xyz resolution. Cell somas in the ganglion cell layer (GCL) in large mammals appeared predominantly bright with dark contours, while in rodents, GCL somas appeared dark with bright contours. RGC axon to soma junctions could be traced in the three-dimensional (3D) image stacks. Time series revealed undulation of retinal tissue samples over 48 hours, though no degradation of individual cells was detected, while paraformaldehyde fixation caused increased scattering and shrinkage. CONCLUSIONS: Full-field OCT reveals micrometric morphologic detail in the retina without the use of contrast agents. We observed interspecies differences in optical properties of GCL somas. Fixation significantly alters retinal transparency hence reducing the visibility of microscopic features. PMID- 27409510 TI - Visible-Light Optical Coherence Tomography Angiography for Monitoring Laser Induced Choroidal Neovascularization in Mice. AB - PURPOSE: This study sought to determine the earliest time-point at which evidence of choroidal neovascularization (CNV) could be detected with visible-light optical coherence tomography angiography (vis-OCTA) in a mouse model of laser induced CNV. METHODS: Visible light-OCTA was used to study laser-induced CNV at different time-points after laser injury to monitor CNV development and measure CNV lesion size. Measurements obtained from vis-OCTA angiograms were compared with histopathologic measurements from isolectin-stained choroidal flatmounts. RESULTS: Choroidal neovascularization area measurements between the vis-OCTA system and isolectin-stained choroidal flatmounts were significantly different in area for days 2 to 4 postlaser injury, and were not significantly different in area for days 5, 7, and 14. Choroidal neovascularization area measurements taken from the stained flatmounts were larger than their vis-OCTA counterparts for all time-points. Both modalities showed a similar trend of CNV size increasing from the day of laser injury until a peak of day 7 postlaser injury and subsequently decreasing by day 14. CONCLUSIONS: The earliest vis-OCTA can detect the presence of aberrant vessels in a mouse laser-induced CNV model is 5 days after laser injury. Visible light-OCTA was able to visualize the maximum of the CNV network 7 days postlaser injury, in accordance with choroidal flatmount immunostaining. Visible light-OCTA is a reliable tool in both detecting the presence of CNV development, as well as accurately determining the size of the lesion in a mouse laser-induced CNV model. PMID- 27409512 TI - Gender-Specific Toxicological Effects of Chronic Exposure to Pure Microcystin-LR or Complex Microcystis aeruginosa Extracts on Adult Medaka Fish. AB - Cyanobacterial blooms often occur in freshwater lakes and constitute a potential health risk to human populations, as well as to other organisms. However, their overall and specific implications for the health of aquatic organisms that are chronically and environmentally exposed to cyanobacteria producing hepatotoxins, such as microcystins (MCs), together with other bioactive compounds have still not been clearly established and remain difficult to assess. The medaka fish was chosen as the experimental aquatic model for studying the cellular and molecular toxicological effects on the liver after chronic exposures (28 days) to environmentally relevant concentrations of pure MC-LR, complex extracts of MC producing or nonproducing cyanobacterial biomasses, and of a Microcystis aeruginosa natural bloom. Our results showed a higher susceptibility of females to the different treatments compared to males at both the cellular and the molecular levels. Although hepatocyte lysis increased with MC-containing treatments, lysis always appeared more severe in the liver of females compare to males, and the glycogen cellular reserves also appeared to decrease more in the liver of females compared to those in the males. Proteomic investigations reveal divergent responses between males and females exposed to all treatments, especially for proteins involved in metabolic and homeostasis processes. Our observations also highlighted the dysregulation of proteins involved in oogenesis in female livers. These results suggest that fish populations exposed to cyanobacteria blooms may potentially face several ecotoxicological issues. PMID- 27409513 TI - Superior Light-Harvesting Heteroleptic Ruthenium(II) Complexes with Electron Donating Antennas for High Performance Dye-Sensitized Solar Cells. AB - Three heteroleptic polypyridyl ruthenium complexes, RC-41, RC-42, and RC-43, with efficient electron-donating antennas in the ancillary ligands were designed, synthesized, and characterized as sensitizers for dye-sensitized solar cell. All the RC dye sensitizers showed remarkable light-harvesting capacity and broadened absorption range. Significantly, RC-43 obtained the lower energy metal-ligand charge transfer (MLCT) band peaked at 557 nm with a high molar extinction coefficient of 27 400 M(-1) cm(-1). In conjunction with TiO2 photoanode of submicrospheres and iodide-based electrolytes, the DSSCs sensitizing with the RC sensitizers, achieved impressively high short-circuit current density (19.04 mA cm(-2) for RC-41, 19.83 mA cm(-2) for RC-42, and 20.21 mA cm(-2) for RC-43) and power conversion efficiency (10.07% for RC-41, 10.52% for RC-42, and 10.78% for RC-43). The superior performances of RC dye sensitizers were attributed to the enhanced light-harvesting capacity and incident-photon-to-current efficiency (IPCE) caused by the introduction of electron-donating antennas in the ancillary ligands. The interfacial charge recombination/regeneration kinetics and electron lifetime were further evaluated by the electrochemical impedance spectroscopy (EIS) and transient absorption spectroscopy (TAS). These data decisively revealed the dependences on the photovoltaic performance of ruthenium sensitizers incorporating electron-donating antennas. PMID- 27409514 TI - Iron Ion and Iron Hydroxide Adsorption to Charge-Neutral Phosphatidylcholine Templates. AB - Surface-sensitive X-ray scattering and spectroscopy techniques reveal significant adsorption of iron ions and iron-hydroxide (Fe(III)) complexes to a charge neutral zwitterionic template of phosphatidylcholine (PC). The PC template is formed by a Langmuir monolayer of dipalmitoyl-PC (DPPC) that is spread on the surface of 2 to 40 MUM FeCl3 solutions at physiological levels of KCl (100 mM). At 40 MUM of Fe(III) as many as ~3 iron atoms are associated with each PC group. Grazing incidence X-ray diffraction measurements indicate a significant disruption in the in-plane ordering of DPPC molecules upon iron adsorption. The binding of iron-hydroxide complexes to a neutral PC surface is yet another example of nonelectrostatic, presumably covalent bonding to a charge-neutral organic template. The strong binding and the disruption of in-plane lipid structure has biological implications on the integrity of PC-derived lipid membranes, including those based on sphingomyelin. PMID- 27409516 TI - Triggering Violence in Psychosis. PMID- 27409515 TI - n->pi* Interactions Are Competitive with Hydrogen Bonds. AB - Because carbonyl groups can participate in both hydrogen bonds and n->pi* interactions, these two interactions likely affect one another. Herein, enhancement of an amidic n->pi* interaction is shown to reduce the ability of beta-keto amides to tautomerize to the enol, indicating decreased hydrogen bonding capacity of the amide carbonyl group. Thus, an n->pi* interaction can have a significant effect on the strength of a hydrogen bond to the same carbonyl group. PMID- 27409517 TI - Polyprenylated Benzoylphloroglucinols with DNA Polymerase Inhibitory Activity from the Fruits of Garcinia schomburgkiana. AB - Chemical investigation of the fruits of Garcinia schomburgkiana collected in Vietnam led to the isolation of eight new schomburgkianones, A-H (1-8), four known (9-12) polyprenylated benzoylphloroglucinols, and four known biflavonoids. The structures of these compounds were elucidated by spectroscopic and chemical means. The absolute configuration at C-40 of 1 and 2 was determined by (1)H NMR analyses of their MPA esters. The configuration of the bicyclo[3.3.1]nonane core of the polyprenylated benzoylphloroglucinols was assigned by comparison of their experimental ECD spectra with those of related compounds. The polyprenylated benzoylphloroglucinols exhibited inhibitory activities against mammalian DNA polymerases alpha and lambda, with IC50 values ranging from 5.0 to 8.8 MUM. Compounds 1, 2, 4, 5, and 9-11 showed cytotoxic effects against HeLa human cervical cancer cells with median lethal dose values lower than 10 MUM. PMID- 27409518 TI - Development of a New Generation of Stable, Tunable, and Catalytically Active Nanoparticles Produced by the Helium Nanodroplet Deposition Method. AB - Nanoparticles (NPs) are revolutionizing many areas of science and technology, often delivering unprecedented improvements to properties of the conventional materials. However, despite important advances in NPs synthesis and applications, numerous challenges still remain. Development of alternative synthetic method capable of producing very uniform, extremely clean and very stable NPs is urgently needed. If successful, such method can potentially transform several areas of nanoscience, including environmental and energy related catalysis. Here we present the first experimental demonstration of catalytically active NPs synthesis achieved by the helium nanodroplet isolation method. This alternative method of NPs fabrication and deposition produces narrowly distributed, clean, and remarkably stable NPs. The fabrication is achieved inside ultralow temperature, superfluid helium nanodroplets, which can be subsequently deposited onto any substrate. This technique is universal enough to be applied to nearly any element, while achieving high deposition rates for single element as well as composite core-shell NPs. PMID- 27409519 TI - Adaptive Resolution Simulation of Supramolecular Water: The Concurrent Making, Breaking, and Remaking of Water Bundles. AB - The adaptive resolution scheme (AdResS) is a multiscale molecular dynamics simulation approach that can concurrently couple atomistic (AT) and coarse grained (CG) resolution regions, i.e., the molecules can freely adapt their resolution according to their current position in the system. Coupling to supramolecular CG models, where several molecules are represented as a single CG bead, is challenging, but it provides higher computational gains and connection to the established MARTINI CG force field. Difficulties that arise from such coupling have been so far bypassed with bundled AT water models, where additional harmonic bonds between oxygen atoms within a given supramolecular water bundle are introduced. While these models simplify the supramolecular coupling, they also cause in certain situations spurious artifacts, such as partial unfolding of biomolecules. In this work, we present a new clustering algorithm SWINGER that can concurrently make, break, and remake water bundles and in conjunction with the AdResS permits the use of original AT water models. We apply our approach to simulate a hybrid SPC/MARTINI water system and show that the essential properties of water are correctly reproduced with respect to the standard monoscale simulations. The developed hybrid water model can be used in biomolecular simulations, where a significant speed up can be obtained without compromising the accuracy of the AT water model. PMID- 27409520 TI - N,N'-Diamidocarbenes: Isolable Divalent Carbons with Bona Fide Carbene Reactivity. AB - Since the first reported isolation of a carbene just over a quarter century ago, the study of such compounds-including stable derivatives-has flourished. Indeed, N-heterocyclic carbenes (NHCs), of which imidazolylidenes and their derivatives are the most pervasive subclass, feature prominently in organocatalysis, as ligands for transition metal catalysts, and as stabilizers of reactive species. However, imidazolylidenes (and many other NHCs) typically lack the reactivity characteristic of electrophilic carbenes, including insertion into unactivated C H bonds, participation in [2 + 1] cycloadditions, and reaction with carbon monoxide. This has led to debates over whether NHCs are truly carbenic in nature or perhaps better regarded as ylides. The fundamental and synthetic utility of transformations that involve electrophilic carbenes has motivated our group and others to expand the reactivity of NHCs and other stable carbenes to encompass electrophilic carbene chemistry. These efforts have led to the development of the diamidocarbenes (DACs), a stable and unique subset of the NHCs that feature carbonyl groups inserted into the N-heterocyclic scaffold. To date, crystalline five-, six-, and seven-membered DACs have been prepared and studied. Unlike imidazolylidenes, which are often designated as prototypical NHCs, the DACs exhibit a reactivity profile similar to that of bona fide carbenes, reactive species that are less "tamed" by heteroatom pi conjugation. The DACs engage in [2 + 1] cycloadditions with electron-rich or -poor alkenes, aldehydes, alkynes, and nitriles, and doing so in a reversible manner in some cases. They also react with isonitriles, reversibly couple to CO, and mediate the dehydrogenation of hydrocarbons. Such rich chemistry may be rationalized in terms of their ambiphilicity: DACs are nucleophilic, as required for some of the reactions above, yet also have electrophilic character, as evidenced by their insertions into unactivated N-H and C-H bonds, including nonacidic derivatives. As will become clear, such reactivity is unique among isolable carbenes. DAC chemistry is expected to find applications in synthesis, dynamic covalent chemistry, and catalysis. For example, the hydrolysis of DAC-derived diamidocyclopropanes and propenes affords carboxylic acids and cyclopropenones, respectively. These new hydrocarboxylation and carbonylation methodologies are significant in that they represent alternatives to processes that typically involve precious metals and gaseous carbon monoxide. Future efforts in this area may involve modifications that transform the stoichiometric conversions facilitated by DACs into catalytic variants. In this context, the reversible binding of CO to DACs is an indication that the latter may serve as a blueprint for the development of more electrophilic, stable carbenes with the capacity to activate other challenging small molecules. PMID- 27409521 TI - Breath Analysis Based on Surface-Enhanced Raman Scattering Sensors Distinguishes Early and Advanced Gastric Cancer Patients from Healthy Persons. AB - Fourteen volatile organic compound (VOC) biomarkers in the breath have been identified to distinguish early gastric cancer (EGC) and advanced gastric cancer (AGC) patients from healthy persons by gas chromatography-mass spectrometry coupled with solid phase microextraction (SPME). Then, a breath analysis approach based on a surface-enhanced Raman scattering (SERS) sensor was developed to detect these biomarkers. Utilizing hydrazine vapor adsorbed in graphene oxide (GO) film, the clean SERS sensor is facilely prepared by in situ formation of gold nanoparticles (AuNPs) on reduced graphene oxide (RGO) without any organic stabilizer. In the SERS sensor, RGO can selectively adsorb and enrich the identified biomarkers from breath as an SPME fiber, and AuNPs well dispersed on RGO endow the SERS sensor with an effective detection of adsorbed biomarkers. Fourteen Raman bands associated with the biomarkers are selected as the fingerprints of biomarker patterns to distinguish persons in different states. The approach has successfully analyzed and distinguished different simulated breath samples and 200 breath samples of clinical patients with a sensitivity of higher than 83% and a specificity of more than 92%. In conclusion, the VOC biomarkers and breath analysis approach in this study can not only diagnose gastric cancer but also distinguish EGC and AGC. This work has great potential for clinical translation in primary screening diagnosis and stage determination of stomach cancer in the near future. PMID- 27409522 TI - Do nasal septal deformities have anything to do with chronic rhinosinusitis? PMID- 27409523 TI - Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men. AB - OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG. PMID- 27409524 TI - Readiness for Implementation of Lung Cancer Screening. A National Survey of Veterans Affairs Pulmonologists. AB - RATIONALE: To mitigate the potential harms of screening, professional societies recommend that lung cancer screening be conducted in multidisciplinary programs with the capacity to provide comprehensive care, from screening through pulmonary nodule evaluation to treatment of screen-detected cancers. The degree to which this standard can be met at the national level is unknown. OBJECTIVES: To assess the readiness of clinical facilities in a national healthcare system for implementation of comprehensive lung cancer screening programs, as compared with the ideal described in policy recommendations. METHODS: This was a cross sectional, self-administered survey of staff pulmonologists in pulmonary outpatient clinics in Veterans Health Administration facilities. MEASUREMENTS AND MAIN RESULTS: The facility-level response rate was 84.1% (106 of 126 facilities with pulmonary clinics); 88.7% of facilities showed favorable provider perceptions of the evidence for lung cancer screening, and 73.6% of facilities had a favorable provider-perceived local context for screening implementation. All elements of the policy-recommended infrastructure for comprehensive screening programs were present in 36 of 106 facilities (34.0%); the most common deficiencies were the lack of on-site positron emission tomography scanners or radiation oncology services. Overall, 26.5% of Veterans Health Administration facilities were ideally prepared for lung cancer screening implementation (44.1% if the policy recommendations for on-site positron emission tomography scanners and radiation oncology services were waived). CONCLUSIONS: Many facilities may be less than ideally positioned for the implementation of comprehensive lung cancer screening programs. To ensure safe, effective screening, hospitals may need to invest resources or coordinate care with facilities that can offer comprehensive care for screening through downstream evaluation and treatment of screen-detected cancers. PMID- 27409525 TI - Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities. AB - BACKGROUND: A total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described. METHODS: Sixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-. RESULTS: Demographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0-14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q- patients (5/11) than non-13q- patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q- patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months-9.5 years). CONCLUSIONS: 13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure. PMID- 27409526 TI - Seasonality and BDNF polymorphism influences depression outcome in patients with atopic dermatitis and psoriasis. AB - OBJECTIVES: To examine the effect of seasonality and rs6265 genotype on depression outcome and brain-derived neurotrophic factor (BDNF) level with dermatitis patients from onset through remission. METHODS: Atopic dermatitis (AD, 56) and psoriasis (PS, 33) patients and healthy controls (HC, 49) were recruited over the 2014 calendar year. Patients were subdivided by immunoglobulin E (IgE) sensitivity (AD only), season and rs6265 genotype. Assessments were performed at onset and week 10 (Hamilton Depression Rating Scale [HAM-D], SCORAD/PASI, IgE, BDNF). Patients received standard corticosteroid and antihistamine interventions. RESULTS: All patients responded to corticosteroid treatment. Seasonally differential outcomes were observed in all groups. HAM-D was elevated at onset and improved over 10 weeks: AD cohort 1 (autumn/winter, AD-1) patients improved and AD cohort 2 (spring/summer, AD-2) patients remained elevated. BDNF levels were elevated in AD and seasonal differential: AD-2 declined at 10 weeks, whereas AD-1 remained high (intrinsic AD) or elevated further (extrinsic AD). PS cohort 2 declined to below control at 10 weeks. AD Val/Val had persistently elevated HAM-D and AD Val/Met were either normal (AD-1) or persistently elevated (AD-2). CONCLUSIONS: Findings presented here suggest a strong influence of seasonality on depression outcome and BDNF expression in AD and PS and likely reflect separate patient populations which differentially respond to environment-based stressors. PMID- 27409527 TI - Surgical resection of two independent primary intimal sarcomas in the left atrium. AB - Primary intimal sarcoma of the heart is an extremely rare tumor that is known to have a very poor prognosis. We present a case of a 65-year-old man who suffered from deteriorating congestive heart failure due to a severe mitral stenosis caused by a large mobile left atrial tumor. The patient underwent an emergency operation of the tumor in the left atrium. The tumor was attached to the inferior wall of the left atrium. After the resection of the tumor, a second tumor on the interatrial septum, which had not been detected in the preoperative investigation, was discovered and resected. The patient developed acute respiratory failure soon after the operation and succumbed to his illness. The appearance of the main tumor was cauliflower-like, which strongly suggested the possibility of malignancy. Immunohistochemistry revealed that the neoplastic cells were positive for vimentin, desmin, p16, and especially murine double minute 2 (MDM-2). The first tumor was CD34 positive and cdk4 negative, but the second tumor was more anaplastic and CD34 negative and cdk4 positive, which suggests a different origin of the two tumors. The two tumors were diagnosed as intimal sarcomas by MDM-2, which is currently considered a conclusive marker. This is an exceptionally rare case of two simultaneous and possibly independent primary intimal sarcomas in the left atrium. PMID- 27409529 TI - Editor's mail. PMID- 27409531 TI - What's happening in medicine! PMID- 27409530 TI - Problems/Solutions. PMID- 27409528 TI - Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum-Pressure Accelerated Movement (V-PAM). AB - Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum-Pressure Accelerated Movement (V-PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead-end channels and closed chambers. Operation of the V-PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas-permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V-PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V-PAM for rapid filling of temperature-sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V-PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs-on-chips, and biomimetic studies. PMID- 27409532 TI - Washington background. PMID- 27409533 TI - Introduction. PMID- 27409534 TI - Ready Source on Gastrointestinal Disorders. PMID- 27409535 TI - Therapeutic Index to Advertisers. PMID- 27409537 TI - Scanning sports. PMID- 27409536 TI - Double red blood cell collection: comparison of three apheresis systems. AB - BACKGROUND: We compared three instruments for double red blood cell (DRBC) collection to efficiently optimize our RBC inventory. STUDY DESIGN AND METHODS: Instruments compared were the TerumoBCT Trima Accel (Trima), the Fenwal Alyx (Alyx), and the Haemonetics MCS+ 8150 (MCS+). Forty consecutive collections (80 products) per instrument were evaluated for hemoglobin (Hb) content, leukoreduction, collection time, instrument efficiency, donor acceptance, and reactions. The total number of whole blood donors who could be eligible for DRBC collection was analyzed. All collections were as per the manufacturer recommendations with target volume of 360 or 400mL. Leukoreduction was integral to the collection procedure for the Alyx and Trima, while it was a separate process for the MCS+. RESULTS: The total numbers of whole blood donors who could be eligible for DRBC collection were 10,116 for the MCS+, 9378 for the Alyx, and 8573 for the Trima. All units collected had more than 42.5 g of Hb. Mean Hb levels were as follows: Trima, 59.2 g; Alyx, 56.8 g; and MCS+, 51.5 g. Donor times for the Trima, Alyx, and MCS+ were 52, 45, and 52 minutes, respectively. Technician times for the Trima, Alyx, and MCS+ (without filtration) were 87, 73, and 64 minutes. All collected products had fewer than 5 * 10(6) white blood cells. CONCLUSIONS: All three instruments would be capable of collecting an acceptable leukoreduced DRBC product. The Alyx was most portable, with the shortest donor time and total technician time (considering filtration time) and highest collection efficiency and would collect from more donors than the Trima. We thus chose the Alyx as it best fits the specific needs of our center. PMID- 27409538 TI - Letters. PMID- 27409541 TI - A need to know. PMID- 27409542 TI - The Very Young Athlete. PMID- 27409544 TI - Coming in sportsmedicine. PMID- 27409543 TI - Brief reports. PMID- 27409545 TI - American Academy of Pediatrics. PMID- 27409546 TI - Living With Style. PMID- 27409547 TI - Heart Rate and Energy Expenditure During Aqua Dynamics. AB - In brief: The heart rate, oxygen uptake, and energy expenditure of three young women were measured during 20-minute low-gear, 30-minute middle-gear, and 60 minute high-gear aqua dynamics workouts. All three workouts were moderate in intensity, eliciting average heart rates of 132 to 143 beats min(-1) (70% to 77% HR max), average oxygen uptakes of 1.2 to 1.3 liters min(-1) (51% to 57% VO2 max), and average energy expenditures of 5.9 to 6.5 kcals min(-1) The findings indicate that aqua dynamics could be a beneficial conditioning program for people who have relatively low physical work capacity and enjoy swimming but cannot conveniently engage in lap swimming. PMID- 27409548 TI - Proper Fitting and Use of Crutches. AB - In brief: Injured athletes who need crutches must be fitted correctly and taught their proper use to help prevent further injury, undue complications, and discouragement. Crutches should reach to about two finger widths below the armpit, and the handgrip should be adjusted so the elbow is flexed 25 degrees to 30 degrees with the wrist straight. The weight should be supported through the palms on the handgrips. The three-point gait is used when only one foot, ankle, or knee is injured. Proper instruction is extremely important for negotiating stairs. PMID- 27409549 TI - The Shrugged-Off Shoulder: A Comparison of Patients With Recurrent Shoulder Subluxations and Dislocations. AB - In brief: Patients with recurrent anterior shoulder subluxations and dislocations are compared in terms of recurrences, delays in diagnoses, and treatments. Based on these criteria, the subluxers experienced substantially more disability than the dislocators. Since shoulder instability is such a frequent problem in athletes (sports caused the initial episode in nearly 70% of the patients), professionals who deal with athletic injuries must be aware of the shoulder subluxation syndrome, recognize It early, and quickly initiate appropriate treatments. PMID- 27409550 TI - Skin Disorders in Athletes: Identification and Management. AB - In brief: Diagnosis of common skin problems in athletes is sometimes complicated by secondary changes due to various locker room remedies, sweat, and trauma. The 15 categories of skin problems discussed in this article can be differentiated and accurately diagnosed if the physician considers the possible clinical presentations and the patient's history, and if he or she performs the appropriate microscopic studies and cultures. Treatment must be specific, and the patient must have a clear understanding of the dangers of not stringently following instructions. Early diagnosis, supervision of treatment, and instituting preventive measures will minimize healing time and prevent spreading and/or recurrences of these disorders. PMID- 27409551 TI - Is Lactic Acid Related to Delayed-Onset Muscle Soreness? AB - In brief: The authors tested the hypothesis that delayed-onset muscular soreness after running is related to the production of lactic acid during the exercise. Blood lactic acid concentration was measured before and during 45 minutes of treadmill running, one time on the level and once at a-10% incline. Blood lactic acid concentration and subjective sensations of muscular soreness were assessed at intervals for 72 hours after the runs. Lactic acid concentration was significantly increased during running on the level, but subjects experienced no significant postexercise muscular soreness. Lactic acid was never elevated in downhill runners, but subjects experienced significant delayed-onset soreness. Results indicated that lactic acid is not related to exercise-induced delayed onset muscle soreness. PMID- 27409552 TI - Carboxyhemoglobin Levels in New York City Runners. AB - In brief: Carboxyhemoglobin (COHb) blood levels were measured in 16 New York City runners before and after one-half hour of exercise. Subjects exercised along a highway and in a park under similar weather conditions during rush-hour traffic. These COHb levels were compared to those of ten healthy, nonsmoking volunteers who stood quietly for the same time period at one of the exercise locations. The runners' COHb rose during exercise at both locations from 1.7% to 5.1% and from 1.3% to 4.2% (p <.001). COHb levels also increased in the nonrunners but to a lesser extent (from 0.83% to 2.44%, p <.05). The data indicate that running or standing near traffic in an urban area raises COHb to the levels found in chronic cigarette smokers. These findings quantify potentially harmful exposure to carbon monoxide fumes in an urban environment. PMID- 27409553 TI - Epidural Hematoma in Lacrosse. AB - In brief: Several hours after being hit by a lacrosse stick in the left temporoparietal area slightly anterior to the ear, a lacrosse player was found unresponsive and wrapped in a blanket in his dormitory room. He had not lost consciousness during the game, sat out only five minutes, and completed the game. His Glasgow Coma Scale score was 12 of a possible 15. A CT scan showed an epidural hematoma and a skull fracture. He underwent an immediate left temporoparietal craniotomy and evacuation of the epidural hematoma. He recovered fully and requested permission to return to play six months after the injury. The authors think that an improved lacrosse helmet design would help prevent this type of injury. PMID- 27409554 TI - Primary Care Physicians: First Stop for Exercise Advice? AB - Patients are urged to consult a physician before starting an exercise program, but how many do and what advice do they receive? PMID- 27409555 TI - A Profile of the College Female Athlete. AB - The number of women participating in collegiate sports has more than doubled in the last five years and is believed to be more than 10 million. Women compete in 77 collegiate championships in 18 sports, and athletic scholarships for women are increasing. PMID- 27409556 TI - Weight Training and Weight Lifting: Information for the Pediatrician. PMID- 27409558 TI - The Effect of Exercise on Cholesterol Levels. PMID- 27409557 TI - You Can't Exhaust Florida's Gulf Coast Keys. AB - South of Sarasota, a tiny archipelago curves neatly out Into the Gulf around a lovely coastal sound. The pearl In the chain is called Cabbage Key. PMID- 27409559 TI - An Athletic Training Room for 10,000. PMID- 27409562 TI - Is Excessive Sweating Healthy? PMID- 27409560 TI - David Costill: Human Performance Is His Business. AB - Dave Costill is as committed to exercise physiology research as he is to getting the results to athletes, but sometimes he risks a loss of credibility with scientific peers. PMID- 27409563 TI - Eye Movements of Radiologists Reflect Expertise in CT Study Interpretation: A Potential Tool to Measure Resident Development. AB - Purpose To establish potential markers of visual expertise in eye movement (EM) patterns of early residents, advanced residents, and specialists who interpret abdominal computed tomography (CT) studies. Materials and Methods The institutional review board approved use of anonymized CT studies as research materials and to obtain anonymized eye-tracking data from volunteers. Participants gave written informed consent. Early residents (n = 15), advanced residents (n = 14), and specialists (n = 12) viewed 26 abdominal CT studies as a sequence of images at either 3 or 5 frames per second while EMs were recorded. Data were analyzed by using linear mixed-effects models. Results Early residents' detection rate decreased with working hours (odds ratio, 0.81; 95% confidence interval [CI]: 0.73, 0.91; P = .001). They detected less of the low visual contrast (but not of the high visual contrast) lesions (45% [13 of 29]) than did specialists (62% [18 of 29]) (odds ratio, 0.39; 95% CI: 0.25, 0.61; P < .001) or advanced residents (56% [16 of 29]) (odds ratio, 0.55; 95% CI: 0.33, 0.93; P = .024). Specialists and advanced residents had longer fixation durations at 5 than at 3 frames per second (specialists: beta = .01; 95% CI: .004, .026; P = .008; advanced residents: beta = .04; 95% CI: .03, .05; P < .001). In the presence of lesions, saccade lengths of specialists shortened more than those of advanced (beta = .02; 95% CI: .007, .04; P = .003) and of early residents (beta = .02; 95% CI: .008, 0.04; P = .003). Irrespective of expertise, high detection rate correlated with greater reduction of saccade length in the presence of lesions (beta = -.10; 95% CI: -.16, -.04; P = .002) and greater increase at higher presentation speed (beta = .11; 95% CI: .04, .17; P = .001). Conclusion Expertise in CT reading is characterized by greater adaptivity in EM patterns in response to the demands of the task and environment. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27409564 TI - Hepatic Thermal Ablation: Effect of Device and Heating Parameters on Local Tissue Reactions and Distant Tumor Growth. AB - Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammation and distant pro-oncogenic effects compared with hepatic radiofrequency ablation (RFA) in an animal model. Materials and Methods In this institutional Animal Care and Use Committee-approved study, F344 rats (150 gm, n = 96) with subcutaneous R3230 breast adenocarcinoma tumors had normal non-tumor bearing liver treated with RFA (70 degrees C * 5 minutes), rapid higher-power MWA (20 W * 15 seconds), slower lower-power MWA (5 W * 2 minutes), or a sham procedure (needle placement without energy) and were sacrificed at 6 hours to 7 days (four time points; six animals per arm per time point). Ablation settings produced 11.4 mm +/- 0.8 of coagulation for all groups. Distant tumor growth rates were determined to 7 days after treatment. Liver heat shock protein (HSP) 70 levels (at 72 hours) and macrophages (CD68 at 7 days), tumor proliferative indexes (Ki-67 and CD34 at 7 days), and serum and tissue levels of interleukin 6 (IL-6) at 6 hours, hepatocyte growth factor (HGF) at 72 hours, and vascular endothelial growth factor (VEGF) at 72 hours after ablation were assessed. All data were expressed as means +/- standard deviations and were compared by using two-tailed t tests and analysis of variance for selected group comparisons. Linear regression analysis of tumor growth curves was used to determine pre- and posttreatment growth curves on a per-tumor basis. Results At 7 days, hepatic ablations with 5-W MWA and RFA increased distant tumor size compared with 20-W MWA and the sham procedure (5-W MWA: 16.3 mm +/- 1.1 and RFA: 16.3 mm +/- 0.9 vs sham: 13.6 mm +/- 1.3, P < .01, and 20-W MWA: 14.6 mm +/- 0.9, P < .05). RFA and 5-W MWA increased postablation tumor growth rates compared with the 20-W MWA and sham arms (preablation growth rates range for all arms: 0.60-0.64 mm/d; postablation: RFA: 0.91 mm/d +/- 0.11, 5-W MWA: 0.91 mm/d +/- 0.14, P < .01 vs pretreatment; 20-W MWA: 0.69 mm/d +/- 0.07, sham: 0.56 mm/d +/- 1.15; P = .48 and .65, respectively). Tumor proliferation (Ki-67 percentage) was increased for 5-W MWA (82% +/- 5) and RFA (79% +/- 5), followed by 20-W MWA (65% +/- 2), compared with sham (49% +/- 5, P < .01). Likewise, distant tumor microvascular density was greater for 5-W MWA and RFA (P < .01 vs 20-W MWA and sham). Lower-energy MWA and RFA also resulted in increased HSP 70 expression and macrophages in the periablational rim (P < .05). Last, IL-6, HGF, and VEGF elevations were seen in 5 W MWA and RFA compared with 20-W MWA and sham (P < .05). Conclusion Although hepatic MWA can incite periablational inflammation and increased distant tumor growth similar to RFA in an animal tumor model, higher-power, faster heating protocols may potentially mitigate such undesired effects. (c) RSNA, 2016. PMID- 27409565 TI - Predictive abilities of the HAS-BLED and ORBIT bleeding risk scores in non warfarin anticoagulated atrial fibrillation patients: An ancillary analysis from the AMADEUS trial. AB - BACKGROUND: Simple bleeding risk scores have been proposed to predict bleeding events, in patients anticoagulated using non-warfarin anticoagulants. We compared the relative predictive values of two bleeding risk scores, HAS-BLED and ORBIT, in non-warfarin anticoagulated patients with atrial fibrillation (AF). METHODS AND RESULTS: In a post-hoc ancillary analysis of 'clinically relevant bleeding' events amongst 2283 patients in the idraparinux arm in the AMADEUS trial. The two scores performed modestly in predicting both bleeding outcomes, although there was a trend for better HAS-BLED score performance in predicting any clinically relevant bleeding [c-indexes in HAS-BLED vs. ORBIT; 0.61 (95% CI; 0.58-0.64) vs. 0.58 (95% CI; 0.55-0.61); c-index difference=0.03, z-score=1.84, p=0.06)]. Using the HAS-BLED score compared with the ORBIT score correctly and significantly reclassified 15.6% of the population (95% CI: 4.3 to 27.0; p=0.007). Decision curve analyses confirmed the increasing ability to correctly identify patients who would bleed using the HAS-BLED score versus the ORBIT score, over a wide range of thresholds for any clinically relevant bleeding risk predictions. CONCLUSION: In this comparison of the HAS-BLED and ORBIT scores in a cohort of non-warfarin anticoagulated patients with AF, we show that the HAS-BLED score more accurately predicted any clinically relevant bleeding amongst patients with AF who were anticoagulated with a non-warfarin anticoagulant, when compared with the ORBIT score. PMID- 27409566 TI - A case of very late single leaflet detachment after percutaneous edge-to-edge mitral valve repair (PMVR). PMID- 27409567 TI - Liver cytolysis in acute heart failure: What does it mean? Clinical profile and outcomes of a prospective hospital cohort. AB - Abnormal liver function tests (LFTs) are a common manifestation of heart failure (HF). Our purpose was to characterize patients hospitalized for acute HF (AHF) with liver cytolysis, analyze cytolysis predictors and explore its prognostic implications. METHODS: In a prospective cohort study, we enrolled patients with AHF consecutively admitted to the Internal Medicine Department of University Hospital between January 2009 and December 2010, and recorded demographic, clinical, laboratory and echocardiogram parameters. A logistic regression was done to identify cytolysis predictors. In survival analysis primary endpoints were all-cause death, readmission due to AHF, and the combined event of all-cause death and readmission for AHF at 90days of follow-up. RESULTS: Fifty-eight patients had cytolysis at admission. AHF attributed to atrial fibrillation (OR 3.235), higher heart rate at admission (OR 1.028), cold/wet profile at admission (OR 7.12) and ejection fraction <30% (OR 2.316) were independent predictors of cytolysis. Death occurred more frequently during follow-up in the cytolysis group (27.6 vs. 15.1%, p=0.014, respectively). On survival analysis, cytolysis remained an independent predictor of death at 90days when adjusted to age (HR 1.066), male gender (HR 1.884), valvular etiology (HR 2.365), neurologic status at admission (sleepy HR 3.854; confusion HR 3.176) and cardiac output (HR 0.762). CONCLUSION: Cytolysis may be a marker of systemic hypoperfusion, so strategies to improve hemodynamic profile should be considered, especially in the presence of cold/wet clinical profile, AHF attributed to AF, tachycardia, and EF<30%. Cytolysis is associated with higher mortality at 90days in patients with AHF. PMID- 27409568 TI - Prevalence and distribution of ideal cardiovascular health metrics and association with metabolic syndrome in Japanese male workers. PMID- 27409569 TI - Use of remote monitoring in the management of ICD end-of-life: Data from the DECODE registry. PMID- 27409571 TI - Paradoxical Eisenmengerization Reversal of an obligatory shunt. PMID- 27409570 TI - Incidence, timing, predictors and impact of acute heart failure complicating ST segment elevation myocardial infarction in patients treated by primary percutaneous coronary intervention. AB - BACKGROUND: Acute heart failure (AHF) complicating ST-segment elevation myocardial infarction (STEMI) is recognized as an ominous complication. Previous studies mostly reported outcomes of heterogeneous, non-contemporary population. Moreover, few studies assessed the prognosis of AHF according to its timing. This study evaluated incidence, predictors and impact of AHF according to its timing in a homogeneous STEMI patients population treated by primary percutaneous coronary intervention (pPCI). METHODS: Data from 6282 patients included in a prospective multicenter registry were analyzed. Patients with AHF (Killip class>I) were compared to patients without AHF and patients with admission AHF were compared to patients who developed in-hospital AHF. In-hospital mortality was the primary endpoint of the study. Propensity-score matching and multivariable regression were used to adjust for confounders. RESULTS: A total of 1328 patients (21.1%) presented AHF: 739 on admission and 589 during hospitalization. AHF was associated with a markedly increased in-hospital mortality rate (19.9% vs. 0.8%, p<0.001). There was a gradual excess risk with each Killip class and admission AHF patients displayed the highest crude mortality rate (24.1%). By multivariable analysis, AHF was the strongest independent predictor of in-hospital mortality (HR=3.852 (2.303-6.442), p<0.001) without evidence of any difference according to its timing (HR=0.947 (0.638 1.372), p=0.767). These results were consistent after extensive adjustment on baseline characteristics in the matched cohorts. Among other predictors, pPCI beyond guidelines-recommended delays and stent thrombosis were independently associated with AHF. CONCLUSION: AHF regardless of its timing remains a common and dreadful complication of STEMI in the contemporary era. PMID- 27409572 TI - Dried blood spots for newborn screening allows easy determination of a high heteroplasmy rate in severe infantile cardiomyopathy. PMID- 27409573 TI - 17q12 deletion and duplication syndrome in Denmark-A clinical cohort of 38 patients and review of the literature. AB - 17q12 deletions and duplications are two distinct, recurrent chromosomal aberrations usually diagnosed by chromosomal microarray analysis (CMA). The aberrations encompass the genes, HNF1B, LHX1, and ACACA, among others. We here describe a large national cohort of 12 phenotyped patients with 17q12 deletions and 26 phenotyped patients with 17q12 duplications. The total cohort includes 19 index patients and 19 family members. We also reviewed the literature in order to further improve the basis for the counseling. We emphasize that renal disease, learning disability, behavioral abnormalities, epilepsy, autism, schizophrenia, structural brain abnormalities, facial dysmorphism, and joint laxity are features seen in both the 17q12 deletion syndrome and the reciprocal 17q12 duplication syndrome; and we extend the list of features seen in both patient categories to include strabismus, esophageal defects, and duodenal atresia. Delayed language development, learning disability, kidney involvement, and eye dysmorphism and strabismus were the most consistently shared features among patients with 17q12 deletion. Patients with 17q12 duplications were characterized by an extremely wide phenotypic spectrum, including a variable degree of learning disabilities, delayed language development, delayed motor milestones, and a broad range of psychiatric and neurological features. This patient group also included adults achieving an academic degree. Assessing index patients and non-index patients separately, our observations illustrate that an overall milder disease burden is seen, in particular in patients with 17q12 duplications who are ascertained on the duplication rather than the phenotype. This evidence may be useful in prenatal counseling. (c) 2016 Wiley Periodicals, Inc. PMID- 27409574 TI - Sigmatropic Rearrangement of Vinyl Aziridines: Expedient Synthesis of Cyclic Sulfoximines from Chiral Sulfinimines. AB - A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, and tolerates a wide substrate scope. A one-pot process starting directly from sulfinimines provides access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine, by transformation of a cyclic sulfoximine into a pyrroline, is also disclosed. PMID- 27409575 TI - Hospital workers bypass traditional occupational injury reporting systems when reporting patient and visitor perpetrated (type II) violence. AB - BACKGROUND: Under-reporting of type II (patient/visitor-on-worker) violence by workers has been attributed to a lack of essential event details needed to inform prevention strategies. METHODS: Mixed methods including surveys and focus groups were used to examine patterns of reporting type II violent events among ~11,000 workers at six U.S. hospitals. RESULTS: Of the 2,098 workers who experienced a type II violent event, 75% indicated they reported. Reporting patterns were disparate including reports to managers, co-workers, security, and patients' medical records-with only 9% reporting into occupational injury/safety reporting systems. Workers were unclear about when and where to report, and relied on their own "threshold" of when to report based on event circumstances. CONCLUSIONS: Our findings contradict prior findings that workers significantly under-report violent events. Coordinated surveillance efforts across departments are needed to capture workers' reports, including the use of a designated violence reporting system that is supported by reporting policies. Am. J. Ind. Med. 59:853-865, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27409576 TI - Gray level Co-occurrence Matrices (GLCM) to assess microstructural and textural changes in pre-implantation embryos. AB - The preimplantation embryo is extraordinarily sensitive to environmental signals and events such that perturbations can alter embryo metabolism and program an altered developmental trajectory, ultimately affecting the phenotype of the adult individual; indeed, the physical environment associated with in vitro embryo culture can attenuate development. Defining the underlying metabolic changes and mechanisms, however, has been limited by the imaging technology used to evaluate metabolites and structural features in the embryo. Here, we assessed the impact of in vitro fertilization and culture on mouse embryos using three metabolic markers: peroxyfluor 1 (a reporter of hydrogen peroxide), monochlorobimane (a reporter of glutathione), and Mitotracker Deep Red (a marker of mitochondria). We also evaluated the distribution pattern of histone 2AX gamma (gammaH2AX) in the nuclei of 2- and 8-cell embryos and blastocysts to investigate the degree of DNA damage caused by in vitro embryo culture. In vitro-fertilized embryos, in vivo developed embryos, and in vivo-fertilized embryos recovered and cultured in vitro were compared at the 2-, 8-cell, and blastocyst stages. In addition to assessments based on fluorescence intensity, textural analysis using Gray Level Co-occurrence Matrix (GLCM), a statistical approach that assesses texture within an image, was used to evaluate peroxyfluor 1, monochlorobimane, and Mitotracker Deep Red staining in an effort to develop a robust metric of embryo quality. Our data provide strong evidence of modified metabolic parameters identifiable as altered fluorescence texture in embryos developed in vitro. Thus, texture analysis approach may provide a means of gaining additional insight into embryo programming beyond conventional measurements of staining intensity for metabolic markers. Mol. Reprod. Dev. 83: 701-713, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27409577 TI - Multiple myeloma: disease response assessment. AB - Precise assessment of response to therapy is of high importance in every phase of multiple myeloma (MM). In addition to the well-established role of monoclonal protein for clinical monitoring, several methods of minimal residual disease evaluation, both inside and outside the bone marrow (BM), are to date available. Next generation flow cytometry and sequencing are probably the best approaches at the BM level, being highly sensitive and uniformly applied. FDG PET/CT is the best imaging technique for evaluating and monitoring response to therapy outside the BM. Functional whole-body MRI techniques (DCE and DWI) seem promising for response evaluation and need further studies. Standardization of most of these techniques is in progress. PMID- 27409578 TI - Early stage, bulky Hodgkin lymphoma patients have a favorable outcome when treated with or without consolidative radiotherapy: potential role of PET scan in treatment planning. PMID- 27409579 TI - Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases. AB - BACKGROUND: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. METHODS: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. RESULTS: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. CONCLUSIONS: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests. PMID- 27409580 TI - Association between opioid use and readmission following liver transplantation. AB - The aim of this study was to assess the independent association between pre transplant prescription opioid use and readmission following liver transplantation. We reviewed the medical records of all patients at a single medical center undergoing primary, single-organ, liver transplantation from 2004 to 2014. We assessed factors associated with hospital readmission 30 days and 1 year after hospital discharge using multivariable competing risk regression models. Among 1056 transplant recipients, 49 (4.6%) were prescribed pre transplant prescription opioids. Readmission occurred in 421 (40%) patients within 30 days and 689 (65%) within 1 year. Patients with pre-transplant opioid use had a significantly higher risk of readmission at 30 days (HR 1.7; 95% CI 1.1 2.5) and a non-significantly elevated risk at 1 year (HR 1.4; 95% CI 1.0-1.9) when controlling for other potential confounders. Although pain was the major reason for readmission in only 12 (3%) patients at 30 days and 33 (6%) patients at 1 year, pre-transplant opioid use was significantly associated with pain related readmission at both time points. In conclusion, prescription opioid use pre-transplantation was significantly associated with all-cause 30-day readmissions and pain-related readmissions at 30 days and 1 year. PMID- 27409583 TI - Comparative Study on Two Different Methods for Determination of Hydraulic Conductivity of HeLa Cells During Freezing. AB - BACKGROUND: The measurement of hydraulic conductivity of the cell membrane is very important for optimizing the protocol of cryopreservation and cryosurgery. There are two different methods using differential scanning calorimetry (DSC) to measure the freezing response of cells and tissues. Devireddy et al. presented the slow-fast-slow (SFS) cooling method, in which the difference of the heat release during the freezing process between the osmotically active and inactive cells is used to obtain the cell membrane hydraulic conductivity and activation energy. Luo et al. simplified the procedure and introduced the single-slow (SS) cooling protocol, which requires only one cooling process although different cytocrits are required for the determination of the membrane transport properties. To the best of our knowledge, there is still a lack of comparison of experimental processes and requirements for experimental conditions between these two methods. This study made a systematic comparison between these two methods from the aforementioned aspects in detail. METHODS: The SFS and SS cooling methods mentioned earlier were utilized to obtain the reference hydraulic conductivity (Lpg) and activation energy (ELp) of HeLa cells by fitting the model to DSC data. RESULTS: With the SFS method, it was determined that Lpg = 0.10 MUm/(min.atm) and ELp = 22.9 kcal/mol; whereas the results obtained by the SS cooling method showed that Lpg = 0.10 MUm/(min.atm) and ELp = 23.6 kcal/mol. CONCLUSIONS: The results indicated that the values of the water transport parameters measured by two methods were comparable. In other words, the two parameters can be obtained by comparing the heat releases between two slow cooling processes of the same sample according to the SFS method. However, the SS method required analyzing heat releases of samples with different cytocrits. Thus, more experimental time was required. PMID- 27409582 TI - Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study. AB - Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors. PMID- 27409584 TI - The Power of Three: Coral Reefs, Seagrasses and Mangroves Protect Coastal Regions and Increase Their Resilience. AB - Natural habitats have the ability to protect coastal communities against the impacts of waves and storms, yet it is unclear how different habitats complement each other to reduce those impacts. Here, we investigate the individual and combined coastal protection services supplied by live corals on reefs, seagrass meadows, and mangrove forests during both non-storm and storm conditions, and under present and future sea-level conditions. Using idealized profiles of fringing and barrier reefs, we quantify the services supplied by these habitats using various metrics of inundation and erosion. We find that, together, live corals, seagrasses, and mangroves supply more protection services than any individual habitat or any combination of two habitats. Specifically, we find that, while mangroves are the most effective at protecting the coast under non storm and storm conditions, live corals and seagrasses also moderate the impact of waves and storms, thereby further reducing the vulnerability of coastal regions. Also, in addition to structural differences, the amount of service supplied by habitats in our analysis is highly dependent on the geomorphic setting, habitat location and forcing conditions: live corals in the fringing reef profile supply more protection services than seagrasses; seagrasses in the barrier reef profile supply more protection services than live corals; and seagrasses, in our simulations, can even compensate for the long-term degradation of the barrier reef. Results of this study demonstrate the importance of taking integrated and place-based approaches when quantifying and managing for the coastal protection services supplied by ecosystems. PMID- 27409585 TI - Integrated Tree-Ring-Radiocarbon High-Resolution Timeframe to Resolve Earlier Second Millennium BCE Mesopotamian Chronology. AB - 500 years of ancient Near Eastern history from the earlier second millennium BCE, including such pivotal figures as Hammurabi of Babylon, Samsi-Adad I (who conquered Assur) and Zimrilim of Mari, has long floated in calendar time subject to rival chronological schemes up to 150+ years apart. Texts preserved on clay tablets provide much information, including some astronomical references, but despite 100+ years of scholarly effort, chronological resolution has proved impossible. Documents linked with specific Assyrian officials and rulers have been found and associated with archaeological wood samples at Kultepe and Acemhoyuk in Turkey, and offer the potential to resolve this long-running problem. Here we show that previous work using tree-ring dating to place these timbers in absolute time has fundamental problems with key dendrochronological crossdates due to small sample numbers in overlapping years and insufficient critical assessment. To address, we have integrated secure dendrochronological sequences directly with radiocarbon (14C) measurements to achieve tightly resolved absolute (calendar) chronological associations and identify the secure links of this tree-ring chronology with the archaeological-historical evidence. The revised tree-ring-sequenced 14C time-series for Kultepe and Acemhoyuk is compatible only with the so-called Middle Chronology and not with the rival High, Low or New Chronologies. This finding provides a robust resolution to a century of uncertainty in Mesopotamian chronology and scholarship, and a secure basis for construction of a coherent timeframe and history across the Near East and East Mediterranean in the earlier second millennium BCE. Our re-dating also affects an unusual tree-ring growth anomaly in wood from Porsuk, Turkey, previously tentatively associated with the Minoan eruption of the Santorini volcano. This tree-ring growth anomaly is now directly dated ~1681-1673 BCE (68.2% highest posterior density range), ~20 years earlier than previous assessments, indicating that it likely has no association with the subsequent Santorini volcanic eruption. PMID- 27409586 TI - Prediction CH4 Emissions from the Wetlands in the Sanjiang Plain of Northeastern China in the 21st Century. AB - The Sanjiang Plain has been experienced significant wetland loss due to expanded agricultural activities, and will be potentially restored by the China National Wetland Conservation Action Plan (NWCP) in future. The objective of this study is to evaluate the impact of future climate warming and wetland restoration on wetland CH4 emissions in northeast China. We used an atmosphere-vegetation interaction model (AVIM2) to drive a modified biogeophysical model (CH4MODwetland), and projected CH4 flux variations from the Sanjiang Plain wetlands under different Representative Concentration Pathway scenarios throughout the 21st century. Model validation showed that the regressions between the observed and simulated CH4 fluxes by the modified model produced an R2 of 0.49 with a slope of 0.87 (p<0.001, n = 237). According to the AVIM2 simulation, the net primary productivity of the Sanjiang Plain wetlands will increase by 38.2 g m-2 yr-1, 116.6 g m-2 yr-1 and 250.4 g m-2 yr-1 under RCP 2.6, RCP 4.5 and RCP 8.5, respectively, by the end of this century. For RCP 2.6, 4.5 and 8.5 scenarios, the CH4 fluxes will increase by 5.7 g m-2 yr-1, 57.5 g m-2 yr-1 and 112.2 g m-2 yr-1. Combined with the wetland restoration, the regional emissions will increase by 0.18-1.52 Tg. The CH4 emissions will be stimulated by climate change and wetland restoration. Regional wetland restoration planning should be directed against different climate scenarios in order to suppress methane emissions. PMID- 27409588 TI - Incidence of Congenital Heart Disease: The 9-Year Experience of the Guangdong Registry of Congenital Heart Disease, China. AB - There are 16.5 million newborns in China annually. However, the incidence of congenital heart disease (CHD) has not been evaluated. In 2004, we launched an active province-wide hospital-based CHD registry in the Guangdong Province of southern China. In this study, we examined the incidence of CHD and its subtypes from 2004 to 2012 and compared our findings to the literature. Our results indicate there is an increasing trend of CHD incidence. The increase in incidence occurred mainly for single lesion and the most common subtypes (e.g., ventricular or atrial septal defect, patent ductus arteriosus). There were no increases found for multiple lesions or more complex subtypes. The proportion of CHD cases that were detected early (e.g., 1 week) increased over time. The incidence of CHD stabilized in 2010-2012 with the average cumulative incidences of 9.7, 9.9, and 11.1 per 1,000 live births at 1 week, 1 month, and 1 year, respectively. The incidences of CHD subtypes were comparable with recent international results. The data did not support previous reports that Asian children have a higher incidence of pulmonary outflow obstructions and lower incidence of transposition of the great arteries. However, there was a lower incidence of left ventricular outflow tract obstructions observed in our series. The increase in CHD incidence observed over time was due to improved detection and diagnosis. The true incidence of CHD in China was approximately 11.1 per 1,000 live births, which is higher than previously reported. PMID- 27409587 TI - Effects of Chicken Interferon Gamma on Newcastle Disease Virus Vaccine Immunogenicity. AB - More effective vaccines are needed to control avian diseases. The use of chicken interferon gamma (chIFNgamma) during vaccination is a potentially important but controversial approach that may improve the immune response to antigens. In the present study, three different systems to co-deliver chIFNgamma with Newcastle disease virus (NDV) antigens were evaluated for their ability to enhance the avian immune response and their protective capacity upon challenge with virulent NDV. These systems consisted of: 1) a DNA vaccine expressing the Newcastle disease virus fusion (F) protein co-administered with a vector expressing the chIFNgamma gene for in ovo and booster vaccination, 2) a recombinant Newcastle disease virus expressing the chIFNgamma gene (rZJ1*L/IFNgamma) used as a live vaccine delivered in ovo and into juvenile chickens, and 3) the same rZJ1*L/IFNgamma virus used as an inactivated vaccine for juvenile chickens. Co administration of chIFNgamma with a DNA vaccine expressing the F protein resulted in higher levels of morbidity and mortality, and higher amounts of virulent virus shed after challenge when compared to the group that did not receive chIFNgamma. The live vaccine system co-delivering chIFNgamma did not enhanced post vaccination antibody response, nor improved survival after hatch, when administered in ovo, and did not affect survival after challenge when administered to juvenile chickens. The low dose of the inactivated vaccine co delivering active chIFNgamma induced lower antibody titers than the groups that did not receive the cytokine. The high dose of this vaccine did not increase the antibody titers or antigen-specific memory response, and did not reduce the amount of challenge virus shed or mortality after challenge. In summary, regardless of the delivery system, chIFNgamma, when administered simultaneously with the vaccine antigen, did not enhance Newcastle disease virus vaccine immunogenicity. PMID- 27409589 TI - Robustness to Faults Promotes Evolvability: Insights from Evolving Digital Circuits. AB - We demonstrate how the need to cope with operational faults enables evolving circuits to find more fit solutions. The analysis of the results obtained in different experimental conditions indicates that, in absence of faults, evolution tends to select circuits that are small and have low phenotypic variability and evolvability. The need to face operation faults, instead, drives evolution toward the selection of larger circuits that are truly robust with respect to genetic variations and that have a greater level of phenotypic variability and evolvability. Overall our results indicate that the need to cope with operation faults leads to the selection of circuits that have a greater probability to generate better circuits as a result of genetic variation with respect to a control condition in which circuits are not subjected to faults. PMID- 27409590 TI - A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M. tuberculosis Infected South Africans. AB - We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb), in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context of an infection and human population setting. We determined the epitope repertoire of eleven representative Mtb antigens and a large panel of previously defined Mtb epitopes. We estimated that our analytic methods detected 50-75% of the total response in a cohort of 63 individuals. As expected, responses were highly heterogeneous, with responses to a total of 125 epitopes detected. The 66 top epitopes provided 80% coverage of the responses identified in our study. Using a panel of 48 HLA class II-transfected antigen-presenting cells, we determined HLA class II restrictions for 278 epitope/donor recognition events (36% of the total). The majority of epitopes were restricted by multiple HLA alleles, and 380 different epitope/HLA combinations comprised less than 30% of the estimated Mtb specific response. Our results underline the complexity of human T cell responses at a population level. Efforts to capture and characterize this broad and highly HLA promiscuous Mtb-specific T cell epitope repertoire will require significant peptide multiplexing efforts. We show that a comprehensive "megapool" of Mtb peptides captured a large fraction of the Mtb-specific T cells and can be used to characterize this response. PMID- 27409593 TI - Effects of audiovisual distraction on children's behaviour during dental treatment: a randomized controlled clinical trial. AB - AIM: Dental anxiety leads to undesirable distresses such as avoidance of dental treatment and increase stress among caregivers that consequently affect the treatment quality. The aim of this study was therefore to evaluate the effectiveness of viewing videotaped cartoons using an eyeglass system (i theatreTM) as an audiovisual (AV) distraction technique on behaviour and anxiety in children receiving dental restorative treatment. METHODS: Fifty-six consecutive children patients who presented for treatment and met inclusion criteria were included and randomly divided into two groups; a control group without distraction (CTR-group) and a distraction-group (AV-group). Three dental treatment visits were provided for each patient. Anxiety and cooperative behaviour were assessed with the Facial Image Scale (FIS) and the Modified Venham's clinical ratings of anxiety and cooperative behaviour scale (MVARS). The vital signs, blood pressure and pulse were also taken. RESULTS: The AV-group showed significantly lower MVARS scores than the CTR-group (p = 0.029), and the scores decreased significantly during treatment in the AV-group (p = 0.04). Further, the pulse rate was significantly increased in the CTR-group during injection with local anaesthesia (p = 0.02), but not in the AV-group. CONCLUSION: AV distraction seems to be an effective method in reducing fear and anxiety in children during dental treatment. Further, children who used eyeglass goggle display as a distraction tool during dental treatment reported not only less anxiety than control groups but also showed more positive responses after injection with local anaesthesia. Hence, AV-distraction seems to be a useful tool to decrease the distress and dental anxiety during dental treatment. PMID- 27409591 TI - Molecular Diversity between Salivary Proteins from New World and Old World Sand Flies with Emphasis on Bichromomyia olmeca, the Sand Fly Vector of Leishmania mexicana in Mesoamerica. AB - BACKGROUND: Sand fly saliva has been shown to have proteins with potent biological activities, salivary proteins that can be used as biomarkers of vector exposure, and salivary proteins that are candidate vaccines against different forms of leishmaniasis. Sand fly salivary gland transcriptomic approach has contributed significantly to the identification and characterization of many of these salivary proteins from important Leishmania vectors; however, sand fly vectors in some regions of the world are still neglected, as Bichromomyia olmeca (formerly known as Lutzomyia olmeca olmeca), a proven vector of Leishmania mexicana in Mexico and Central America. Despite the importance of this vector in transmitting Leishmania parasite in Mesoamerica there is no information on the repertoire of B. olmeca salivary proteins and their relationship to salivary proteins from other sand fly species. METHODS AND FINDINGS: A cDNA library of the salivary glands of wild-caught B. olmeca was constructed, sequenced, and analyzed. We identified transcripts encoding for novel salivary proteins from this sand fly species and performed a comparative analysis between B. olmeca salivary proteins and those from other sand fly species. With this new information we present an updated catalog of the salivary proteins specific to New World sand flies and salivary proteins common to all sand fly species. We also report in this work the anti-Factor Xa activity of Lofaxin, a salivary anticoagulant protein present in this sand fly species. CONCLUSIONS: This study provides information on the first transcriptome of a sand fly from Mesoamerica and adds information to the limited repertoire of salivary transcriptomes from the Americas. This comparative analysis also shows a fast degree of evolution in salivary proteins from New World sand flies as compared with Old World sand flies. PMID- 27409594 TI - Temporal 18O and deuterium variations in hydrologic components of a small watershed during a typhoon event. AB - The differences between delta18O and delta2H in throughfall and open rainfall were studied for a selected typhoon event in a watershed within the Taihu Lake drainage basin, eastern China. In this event, the isotopic composition of precipitation exhibited a strong temporal variation. Comparison results show that an isotopic composition difference existed not only between gross rainfall and average incremental rainfall, but also between different calculation methods used to derive average. The differences between incremental precipitation and throughfall isotopic composition were observed in this study. Considering the temporal variation in rainfall and throughfall during this typhoon event, the incremental value can have an effect on hydrograph separation more accurately in evaluating the importance of 'new' water. In addition, isotopic fluctuations of surface water and groundwater differed from those of rainfall and throughfall throughout the event. PMID- 27409595 TI - Comparable Allogeneic Hematopoietic Cell Transplantation Outcome of a Haplo Identical Family Donor with an Alternative Donor in Adult Aplastic Anemia. AB - We performed a study on allogeneic hematopoietic cell transplantation (alloHCT) from an HLA-haplo-identical familial donor (haploFD) using a busulfan-fludarabine antithymocyte globulin conditioning regimen for severe aplastic anemia (sAA) and hypoplastic myelodysplastic syndrome. For the comparison between a haploFD and an alternative donor (AD; matched unrelated or partially matched donor) for sAA in adults, we collected haploFD data retrospectively and prospectively. Forty-eight AD cases were selected for the comparison with 16 haploFD cases. All transplantation outcomes except for extensive chronic graft versus host disease (GvHD) were similar. The frequencies of hepatic sinusoidal obstruction syndrome (p = 1.000), acute GvHD (p = 0.769), grade 3/4 acute GvHD (p = 0.258), chronic GvHD (p = 0.173), extensive chronic GvHD (p = 0.099), primary neutrophil engraftment failure (p = 1.000), secondary graft failure (p = 1.000) and platelet engraftment failure (p = 0.505) were similar. Time to neutrophil engraftment was faster in haploFD (p = 0.003), while the cumulative incidence of platelet engraftment was similar (p = 0.505). Overall survival was also similar between AD and haploFD (p = 0.730). In conclusion, alloHCT from haploFD in sAA was comparable with alloHCT from AD, but extensive chronic GvHD seemed frequent in haploFD. Therefore alloHCT from haploFD could be an alternative approach for alloHCT from AD in adult sAA. PMID- 27409597 TI - Protective Effects of Costunolide against Hydrogen Peroxide-Induced Injury in PC12 Cells. AB - Oxidative stress-mediated cellular injury has been considered as a major cause of neurodegenerative diseases including Alzheimer's and Parkinson's diseases. The scavenging of reactive oxygen species (ROS) mediated by antioxidants may be a potential strategy for retarding the diseases' progression. Costunolide (CS) is a well-known sesquiterpene lactone, used as a popular herbal remedy, which possesses anti-inflammatory and antioxidant activity. This study aimed to investigate the protective role of CS against the cytotoxicity induced by hydrogen peroxide (H2O2) and to elucidate potential protective mechanisms in PC12 cells. The results showed that the treatment of PC12 cells with CS prior to H2O2 exposure effectively increased the cell viability. Furthermore, it decreased the intracellular ROS, stabilized the mitochondria membrane potential (MMP), and reduced apoptosis-related protein such as caspase 3. In addition, CS treatment attenuated the cell injury by H2O2 through the inhibition of phosphorylation of p38 and the extracellular signal-regulated kinase (ERK). These results demonstrated that CS is promising as a potential therapeutic candidate for neurodegenerative diseases resulting from oxidative damage and further research on this topic should be encouraged. PMID- 27409596 TI - Photocatalytic Water Splitting-The Untamed Dream: A Review of Recent Advances. AB - Photocatalytic water splitting using sunlight is a promising technology capable of providing high energy yield without pollutant byproducts. Herein, we review various aspects of this technology including chemical reactions, physiochemical conditions and photocatalyst types such as metal oxides, sulfides, nitrides, nanocomposites, and doped materials followed by recent advances in computational modeling of photoactive materials. As the best-known catalyst for photocatalytic hydrogen and oxygen evolution, TiO2 is discussed in a separate section, along with its challenges such as the wide band gap, large overpotential for hydrogen evolution, and rapid recombination of produced electron-hole pairs. Various approaches are addressed to overcome these shortcomings, such as doping with different elements, heterojunction catalysts, noble metal deposition, and surface modification. Development of a photocatalytic corrosion resistant, visible light absorbing, defect-tuned material with small particle size is the key to complete the sunlight to hydrogen cycle efficiently. Computational studies have opened new avenues to understand and predict the electronic density of states and band structure of advanced materials and could pave the way for the rational design of efficient photocatalysts for water splitting. Future directions are focused on developing innovative junction architectures, novel synthesis methods and optimizing the existing active materials to enhance charge transfer, visible light absorption, reducing the gas evolution overpotential and maintaining chemical and physical stability. PMID- 27409598 TI - In Situ Enzymatically Generated Photoswitchable Oxidase Mimetics and Their Application for Colorimetric Detection of Glucose Oxidase. AB - In this study, a simple and amplified colorimetric assay is developed for the detection of the enzymatic activity of glucose oxidase (GOx) based on in situ formation of a photoswitchable oxidase mimetic of PO4(3-)-capped CdS quantum dots (QDs). GOx catalyzes the oxidation of 1-thio-beta-d-glucose to give 1-thio-beta-d gluconic acid which spontaneously hydrolyzes to beta-d-gluconic acid and H2S; the generated H2S instantly reacts with Cd(2+) in the presence of Na3PO4 to give PO4(3-)-stabilized CdS QDs in situ. Under visible-light (lambda >= 400 nm) stimulation, the PO4(3-)-capped CdS QDs are a new style of oxidase mimic derived by producing some active species, such as h+, (*)OH, O2(*-) and a little H2O2, which can oxidize the typical substrate (3,3,5,5-tetramethylbenzydine (TMB)) with a color change. Based on the GOx-triggered growth of the oxidase mimetics of PO4(3-)-capped CdS QDs in situ, we developed a simple and amplified colorimetric assay to probe the enzymatic activity of GOx. The proposed method allowed the detection of the enzymatic activity of GOx over the range from 25 MUg/L to 50 mg/L with a low detection limit of 6.6 MUg/L. We believe the PO4(3-)-capped CdS QDs generated in situ with photo-stimulated enzyme-mimicking activity may find wide potential applications in biosensors. PMID- 27409599 TI - Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives. AB - A small series of tetrahydroindazoles was prepared, starting from 2 acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green method for the synthesis of substituted tetrahydroindazole derivatives. The in vitro antioxidant activity was evaluated using the DPPH and ABTS methods. In these assays, 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) showed moderate DPPH decoloring activity, while 3-methyl-4,5,6,7-tetrahydro-1H indazole (3a), 3-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indazole (3b) and 2-(4 fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) were the most active in the ABTS assay. All compounds were well characterized by IR, 1H-, (13)C-NMR and GC-MS spectroscopy and physical data, while the structure of 4-(3-methyl 4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid (3e) was also determined by single crystal X-ray analysis. PMID- 27409600 TI - Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects. AB - Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, with supercritical fluid extraction highlighted as a promising eco friendly alternative providing exceptional separation and protection from degradation of unstable polyphenols. The protective role of polyphenols against reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and predators results in several beneficial biological activities giving rise to prophylaxis or possibly even to a cure for several prevailing human diseases, especially various cancer types. Omnipresence, specificity of the response and the absence of or low toxicity are crucial advantages of polyphenols as anticancer agents. The main problem represents their low bioavailability and rapid metabolism. One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells. Another, more practiced, solution is the use of mixtures of various polyphenols that bring synergistic effects, resulting in lowering of the required therapeutic dose and in multitargeted action. The combination of polyphenols with existing drugs and therapies also shows promising results and significantly reduces their toxicity. PMID- 27409601 TI - Site-Specific, Covalent Immobilization of Dehalogenase ST2570 Catalyzed by Formylglycine-Generating Enzymes and Its Application in Batch and Semi-Continuous Flow Reactors. AB - Formylglycine-generating enzymes can selectively recognize and oxidize cysteine residues within the sulfatase sub motif at the terminus of proteins to form aldehyde-bearing formylglycine (FGly) residues, and are normally used in protein labeling. In this study, an aldehyde tag was introduced to proteins using formylglycine-generating enzymes encoded by a reconstructed set of the pET28a plasmid system for enzyme immobilization. The haloacid dehalogenase ST2570 from Sulfolobus tokodaii was used as a model enzyme. The C-terminal aldehyde-tagged ST2570 (ST2570CQ) exhibited significant enzymological properties, such as new free aldehyde groups, a high level of protein expression and improved enzyme activity. SBA-15 has widely been used as an immobilization support for its large surface and excellent thermal and chemical stability. It was functionalized with amino groups by aminopropyltriethoxysilane. The C-terminal aldehyde-tagged ST2570 was immobilized to SBA-15 by covalent binding. The site-specific immobilization of ST2570 avoided the chemical denaturation that occurs in general covalent immobilization and resulted in better fastening compared to physical adsorption. The site-specific immobilized ST2570 showed 3-fold higher thermal stability, 1.2 fold higher catalytic ability and improved operational stability than free ST2570. The site-specific immobilized ST2570 retained 60% of its original activity after seven cycles of batch operation, and it was superior to the ST2570 immobilized to SBA-15 by physical adsorption, which loses 40% of its original activity when used for the second time. It is remarkable that the site-specific immobilized ST2570 still retained 100% of its original activity after 10 cycles of reuse in the semi-continuous flow reactor. Overall, these results provide support for the industrial-scale production and application of site-specific, covalently immobilized ST2570. PMID- 27409602 TI - Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer. AB - The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% +/- 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)3(H2O)3]+ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 degrees C with a relatively low lipophilicity (logD = 2.15 +/- 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 +/- 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% +/- 0.17% and 7.87% +/- 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation. PMID- 27409603 TI - MMP-9 Serum Levels in Schizophrenic Patients during Treatment Augmentation with Sarcosine (Results of the PULSAR Study). AB - AIM: Find changes in matrix metallopeptidase-9 (MMP-9) levels during augmentation of antipsychotic treatment with sarcosine and a relationship between schizophrenia symptoms severity and initial level of MMP-9. METHOD: Fifty-eight patients with diagnosis of schizophrenia with predominant negative symptoms participated in a six-month prospective RCT (randomized controlled trial). The patients received two grams of sarcosine (n = 28) or placebo (n = 30) daily. At the beginning, after six weeks and after six months MMP-9 levels were measured. Severity of symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: MMP 9 serum levels were stable after six weeks and six months in both groups. We noted improvement in negative symptoms, general psychopathology and total PANSS score in sarcosine group compared to placebo; however, there was no correlations between serum MMP-9 concentrations and PANSS scores in all assessments. Initial serum MMP-9 concentrations cannot be used as an improvement predictor acquired during sarcosine augmentation. CONCLUSIONS: Our results indicate that either MMP 9 is not involved in the N-methyl-d-aspartate (NMDA)-dependent mechanism of sarcosine action in terms of clinical parameters or sarcosine induced changes in peripheral MMP-9 concentrations cannot be detected in blood assessments. PMID- 27409604 TI - Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status. AB - Tenascin C expression correlates with tumor grade and indicates worse prognosis in several tumors. Epidermal growth factor receptor (EGFR) plays an important role in driving proliferation in many tumors. Loss of E-cadherin function is associated with tumor invasion and metastasis. Thyroid transcription factor-1 (TTF-1) is involved in rearranged during transfection (RET) transcription in Hirschsprung's disease. Tenascin C, EGFR, E-cadherin, TTF-1-expression, and their correlations with RET mutation status were investigated in 30 patients with medullary thyroid carcinoma (MTC) (n = 26) or C-cell hyperplasia (n = 4). Tenascin C was found in all, EGFR in 4/26, E-cadherin in 23/26, and TTF-1 in 25/26 MTC. Tenascin C correlated significantly with tumor proliferation (overall, r = 0.61, p < 0.005; RET-mutated, r = 0.81, p < 0.01). E-cadherin showed weak correlation, whereas EGFR and TTF-1 showed no significant correlation with tumor proliferation. EGFR, E-cadherin, and TTF-1 showed weak correlation with proliferation of RET-mutated tumors. Correlation between TTF-1 and tenascin C, E cadherin, and EGFR was r = -0.10, 0.37, and 0.21, respectively. In conclusion, MTC express tenascin C, E-cadherin, and TTF-1. Tenascin C correlates significantly with tumor proliferation, especially in RET-mutated tumors. EGFR is low, and tumors expressing EGFR do not exhibit higher proliferation. TTF-1 does not correlate with RET mutation status and has a weak correlation with tenascin C, E-cadherin, and EGFR expression. PMID- 27409605 TI - Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution. AB - This follow-up paper completes the author's investigations to explore the in solution structural preferences and relative free energies of all OH-substituted oxazole, thiazole, isoxazole, and isothiazole systems. The polarizable continuum dielectric solvent method calculations in the integral-equation formalism (IEF PCM) were performed at the DFT/B97D/aug-cc-pv(q+(d))z level for the stable neutral tautomers with geometries optimized in dichloromethane and aqueous solution. With the exception of the predictions for the predominant tautomers of the 3OH isoxazole and isothiazole, the results of the IEF-PCM calculations for identifying the most stable tautomer of the given species in the two selected solvents agreed with those from experimental investigations. The calculations predict that the hydroxy proton, with the exception for the 4OH isoxazole and 4OH isothiazole, moves preferentially to the ring nitrogen or to a ring carbon atom in parallel with the development of a C=O group. The remaining, low-fraction OH tautomers will not be observable in the equilibrium compositions. Relative solvation free energies obtained by the free energy perturbation method implemented in Monte Carlo simulations are in moderate accord with the IEF-PCM results, but consideration of the DeltaGsolv/MC values in calculating DeltaG(s)tot maintains the tautomeric preferences. It was revealed from the Monte Carlo solution structure analyses that the S atom is not a hydrogen-bond acceptor in any OH-substituted thiazole or isothiazole, and the OH-substituted isoxazole and oxazole ring oxygens may act as a weak hydrogen-bond acceptor at most. The molecules form 1.0-3.4 solute-water hydrogen bonds in generally unexplored numbers at some specific solute sites. Nonetheless, hydrogen-bond formation is favorable with the NH, C=O and OH groups. PMID- 27409606 TI - Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer. AB - Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54-90); the median prostate-specific antigen was 66 ng/dL (0.1-99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07-0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39-3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy. PMID- 27409607 TI - Regulation of Intestinal Epithelial Calcium Transport Proteins by Stanniocalcin-1 in Caco2 Cells. AB - Stanniocalcin-1 (STC1) is a calcium and phosphate regulatory hormone. However, the exact molecular mechanisms underlying how STC1 affects Ca(2+) uptake remain unclear. Here, the expression levels of the calcium transport proteins involved in transcellular transport in Caco2 cells were examined following over-expression or inhibition of STC1. These proteins include the transient receptor potential vanilloid members (TRPV) 5 and 6, the plasma membrane calcium ATPase 1b (PMCA1b), the sodium/calcium exchanger (NCX1), and the vitamin D receptor (VDR). Both gene and protein expressions of TRPV5 and TRPV6 were attenuated in response to over expression of STC1, and the opposite trend was observed in cells treated with siRNASTC1. To further investigate the ability of STC1 to influence TRPV6 expression, cells were treated with 100 ng/mL of recombinant human STC1 (rhSTC1) for 4 h following pre-transfection with siRNASTC1 for 48 h. Intriguingly, the increase in the expression of TRPV6 resulting from siRNASTC1 was reversed by rhSTC1. No significant effect of STC1 on the expression of PMCA1b, NCX1 or VDR was observed in this study. In conclusion, the effect of STC1 on calcium transport in intestinal epithelia is due to, at least in part, its negative regulation of the epithelial channels TRPV5/6 that mediate calcium influx. PMID- 27409608 TI - Identification of Pathways in Liver Repair Potentially Targeted by Secretory Proteins from Human Mesenchymal Stem Cells. AB - BACKGROUND: The beneficial impact of mesenchymal stem cells (MSC) on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC. METHODS: Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses. RESULTS: MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1) increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM) decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT) and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor) signalling pathways as relevant networks. Relationships to transforming growth factor beta (TGF-beta) and hypoxia-inducible factor 1-alpha (HIF1-alpha) signalling seemed also relevant. CONCLUSION: MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration. PMID- 27409610 TI - Inhibition of AQP1 Hampers Osteosarcoma and Hepatocellular Carcinoma Progression Mediated by Bone Marrow-Derived Mesenchymal Stem Cells. AB - The complex cross-talk between tumor cells and their surrounding stromal environment plays a key role in the pathogenesis of cancer. Among several cell types that constitute the tumor stroma, bone marrow-derived mesenchymal stem cells (BM-MSCs) selectively migrate toward the tumor microenvironment and contribute to the active formation of tumor-associated stroma. Therefore, here we elucidate the involvement of BM-MSCs to promote osteosarcoma (OS) and hepatocellular carcinoma (HCC) cells migration and invasion and deepening the role of specific pathways. We analyzed the function of aquaporin 1 (AQP1), a water channel known to promote metastasis and neoangiogenes. AQP1 protein levels were analyzed in OS (U2OS) and HCC (SNU-398) cells exposed to conditioned medium from BM-MSCs. Tumor cell migration and invasion in response to BM-MSC conditioned medium were evaluated through a wound healing assay and Boyden chamber, respectively. The results showed that the AQP1 level was increased in both tumor cell lines after treatment with BM-MSC conditioned medium. Moreover, BM-MSCs mediated tumor cell migration and invasion were hampered after treatment with AQP1 inhibitor. These data suggest that the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and HCC cell migration and invasion through involvement of AQP1. PMID- 27409609 TI - Hepatocyte and Sertoli Cell Aquaporins, Recent Advances and Research Trends. AB - Aquaporins (AQPs) are proteinaceous channels widespread in nature where they allow facilitated permeation of water and uncharged through cellular membranes. AQPs play a number of important roles in both health and disease. This review focuses on the most recent advances and research trends regarding the expression and modulation, as well as physiological and pathophysiological functions of AQPs in hepatocytes and Sertoli cells (SCs). Besides their involvement in bile formation, hepatocyte AQPs are involved in maintaining energy balance acting in hepatic gluconeogenesis and lipid metabolism, and in critical processes such as ammonia detoxification and mitochondrial output of hydrogen peroxide. Roles are played in clinical disorders including fatty liver disease, diabetes, obesity, cholestasis, hepatic cirrhosis and hepatocarcinoma. In the seminiferous tubules, particularly in SCs, AQPs are also widely expressed and seem to be implicated in the various stages of spermatogenesis. Like in hepatocytes, AQPs may be involved in maintaining energy homeostasis in these cells and have a major role in the metabolic cooperation established in the testicular tissue. Altogether, this information represents the mainstay of current and future investigation in an expanding field. PMID- 27409611 TI - Nuclear Receptor Regulation of Aquaporin-2 in the Kidney. AB - Aquaporin-2 (AQP2) is a vasopressin-regulated water channel responsible for regulating water reabsorption through the apical plasma membrane of the principal cells of renal collecting ducts. It has been found that dysregulation and dysfunction of AQP2 cause many disorders related to water balance in people and animals, including polyuria and dilutional hyponatremia. Classically, AQP2 mRNA and protein expression and its membrane translocation are regulated by systemic vasopressin involving short-term regulation of AQP2 trafficking to and from the apical plasma membrane and long-term regulation of the total amount of the AQP2 protein in the cell. Recently, increasing evidence has demonstrated that collecting duct AQP2 expression and membrane translocation are also under the control of many other local factors, especially nuclear receptors. Here, we briefly review the progress of studies in this area and discuss the role of nuclear receptors in the regulation of water reabsorption via affecting AQP2 expression and function. PMID- 27409612 TI - Strawberry Achenes Are an Important Source of Bioactive Compounds for Human Health. AB - Strawberries are highly appreciated for their taste, nutritional value and antioxidant compounds, mainly phenolics. Fruit antioxidants derive from achenes and flesh, but achene contribution to the total fruit antioxidant capacity and to the bioaccessibility after intake is still unknown. In this work, the content of total phenolic compounds, flavonoids, anthocyanins and antioxidant capacity (TEAC, FRAP and DPPH) of achenes and flesh were compared in non-digested as well as in gastric and intestinal extracts after in vitro digestion. Results showed that, despite strawberry achenes represent a small fraction of the fruit, their contribution to total fruit antioxidant content was more than 41% and accounted for 81% of antioxidant capacity (TEAC). Achenes have higher quantity and different quality of antioxidants in non-digested and digested extracts. Antioxidant release was higher in the in vitro gastric digested extracts, but digestion conditions did not only affect quantity but quality, resulting in differences in antioxidant capacity and highlighting the importance of simulating physiological-like extraction conditions for assessing fruit antioxidant properties on human health. These results give new insights into the use of strawberry achenes as a source of bioactive compounds to be considered in strawberry breeding programs for improving human health. PMID- 27409613 TI - MAL Daylight Photodynamic Therapy for Actinic Keratosis: Clinical and Imaging Evaluation by 3D Camera. AB - Non-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild-moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex((c)) camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1-3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL-PDT's increasing compliance. PMID- 27409614 TI - Neuroprotective Effect of Puerarin on Glutamate-Induced Cytotoxicity in Differentiated Y-79 Cells via Inhibition of ROS Generation and Ca(2+) Influx. AB - Glutamate toxicity is estimated to be the key cause of photoreceptor degeneration in the pathogenesis of retinal degenerative diseases. Oxidative stress and Ca(2+) influx induced by glutamate are responsible for the apoptosis process of photoreceptor degeneration. Puerarin, a primary component of Kudzu root, has been widely used in the clinical treatment of retinal degenerative diseases in China for decades; however, the detailed molecular mechanism underlying this effect remains unclear. In this study, the neuroprotective effect of puerarin against glutamate-induced cytotoxicity in the differentiated Y-79 cells was first investigated through cytotoxicity assay. Then the molecular mechanism of this effect regarding anti-oxidative stress and Ca(2+) hemostasis was further explored with indirect immunofluorescence, flow cytometric analysis and western blot analysis. Our study showed that glutamate induced cell viability loss, excessive reactive oxygen species (ROS) generation, calcium overload and up-regulated cell apoptosis in differentiated Y-79 cells, which effect was significantly attenuated with the pre-treatment of puerarin in a dose-dependent manner. Furthermore, our data indicated that the neuroprotective effect of puerarin was potentially mediated through the inhibition of glutamate-induced activation of mitochondrial dependent signaling pathway and calmodulin-dependent protein kinase II (CaMKII) dependent apoptosis signal-regulating kinase 1(ASK-1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. The present study supports the notion that puerarin may be a promising neuroprotective agent in the prevention of retinal degenerative diseases. PMID- 27409615 TI - Bacteria-Templated NiO Nanoparticles/Microstructure for an Enzymeless Glucose Sensor. AB - The bacterial-induced hollow cylinder NiO (HCNiO) nanomaterial was utilized for the enzymeless (without GOx) detection of glucose in basic conditions. The determination of glucose in 0.05 M NaOH solution with high sensitivity was performed using cyclic voltammetry (CV) and amperometry (i-t). The fundamental electrochemical parameters were analyzed and the obtained values of diffusion coefficient (D), heterogeneous rate constant (ks), electroactive surface coverage (G), and transfer coefficient (alpha-alpha) are 1.75 * 10(-6) cm2/s, 57.65 M( 1).s(-1), 1.45 * 10(-10) mol/cm2, and 0.52 respectively. The peak current of the i-t method shows two dynamic linear ranges of calibration curves 0.2 to 3.5 uM and 0.5 to 250 uM for the glucose electro-oxidation. The Ni(2+)/Ni(3+) couple with the HCNiO electrode and the electrocatalytic properties were found to be sensitive to the glucose oxidation. The green chemistry of NiO preparation from bacteria and the high catalytic ability of the oxyhydroxide (NiOOH) is the good choice for the development of a glucose sensor. The best obtained sensitivity and limit of detection (LOD) for this sensor were 3978.9 uA mM(-1).cm(-2) and 0.9 uM, respectively. PMID- 27409616 TI - Source Authentication for Code Dissemination Supporting Dynamic Packet Size in Wireless Sensor Networks. AB - Code dissemination in wireless sensor networks (WSNs) is a procedure for distributing a new code image over the air in order to update programs. Due to the fact that WSNs are mostly deployed in unattended and hostile environments, secure code dissemination ensuring authenticity and integrity is essential. Recent works on dynamic packet size control in WSNs allow enhancing the energy efficiency of code dissemination by dynamically changing the packet size on the basis of link quality. However, the authentication tokens attached by the base station become useless in the next hop where the packet size can vary according to the link quality of the next hop. In this paper, we propose three source authentication schemes for code dissemination supporting dynamic packet size. Compared to traditional source authentication schemes such as MUTESLA and digital signatures, our schemes provide secure source authentication under the environment, where the packet size changes in each hop, with smaller energy consumption. PMID- 27409617 TI - Mobile Autonomous Sensing Unit (MASU): A Framework That Supports Distributed Pervasive Data Sensing. AB - Pervasive data sensing is a major issue that transverses various research areas and application domains. It allows identifying people's behaviour and patterns without overwhelming the monitored persons. Although there are many pervasive data sensing applications, they are typically focused on addressing specific problems in a single application domain, making them difficult to generalize or reuse. On the other hand, the platforms for supporting pervasive data sensing impose restrictions to the devices and operational environments that make them unsuitable for monitoring loosely-coupled or fully distributed work. In order to help address this challenge this paper present a framework that supports distributed pervasive data sensing in a generic way. Developers can use this framework to facilitate the implementations of their applications, thus reducing complexity and effort in such an activity. The framework was evaluated using simulations and also through an empirical test, and the obtained results indicate that it is useful to support such a sensing activity in loosely-coupled or fully distributed work scenarios. PMID- 27409619 TI - An Optical Sensor for Measuring the Position and Slanting Direction of Flat Surfaces. AB - Automated optical inspection is a very important technique. For this reason, this study proposes an optical non-contact slanting surface measuring system. The essential features of the measurement system are obtained through simulations using the optical design software Zemax. The actual propagation of laser beams within the measurement system is traced by using a homogeneous transformation matrix (HTM), the skew-ray tracing method, and a first-order Taylor series expansion. Additionally, a complete mathematical model that describes the variations in light spots on photoelectric sensors and the corresponding changes in the sample orientation and distance was established. Finally, a laboratory prototype system was constructed on an optical bench to verify experimentally the proposed system. This measurement system can simultaneously detect the slanting angles (x, z) in the x and z directions of the sample and the distance (y) between the biconvex lens and the flat sample surface. PMID- 27409618 TI - Microchambers with Solid-State Phosphorescent Sensor for Measuring Single Mitochondrial Respiration. AB - It is now well established that, even within a single cell, multiple copies of the mitochondrial genome may be present (genetic heteroplasmy). It would be interesting to develop techniques to determine if and to what extent this genetic variation results in functional variation from one mitochondrion to the next (functional heteroplasmy). Measuring mitochondrial respiration can reveal the organelles' functional capacity for Adenosine triphosphate (ATP) production and determine mitochondrial damage that may arise from genetic or age related defects. However, available technologies require significant quantities of mitochondria. Here, we develop a technology to assay the respiration of a single mitochondrion. Our "micro-respirometer" consists of micron sized chambers etched out of borofloat glass substrates and coated with an oxygen sensitive phosphorescent dye Pt(II) meso-tetra(pentafluorophenyl)porphine (PtTFPP) mixed with polystyrene. The chambers are sealed with a polydimethylsiloxane layer coated with oxygen impermeable Viton rubber to prevent diffusion of oxygen from the environment. As the mitochondria consume oxygen in the chamber, the phosphorescence signal increases, allowing direct determination of the respiration rate. Experiments with coupled vs. uncoupled mitochondria showed a substantial difference in respiration, confirming the validity of the microchambers as single mitochondrial respirometers. This demonstration could enable future high-throughput assays of mitochondrial respiration and benefit the study of mitochondrial functional heterogeneity, and its role in health and disease. PMID- 27409620 TI - Highly Sensitive Temperature Sensors Based on Fiber-Optic PWM and Capacitance Variation Using Thermochromic Sensing Membrane. AB - In this paper, we propose a temperature/thermal sensor that contains a Rhodamine B sensing membrane. We applied two different sensing methods, namely, fiber-optic pulse width modulation (PWM) and an interdigitated capacitor (IDC)-based temperature sensor to measure the temperature from 5 degrees C to 100 degrees C. To the best of our knowledge, the fiber-optic PWM-based temperature sensor is reported for the first time in this study. The proposed fiber-optic PWM temperature sensor has good sensing ability; its sensitivity is ~3.733 mV/ degrees C. The designed temperature-sensing system offers stable sensing responses over a wide dynamic range, good reproducibility properties with a relative standard deviation (RSD) of ~0.021, and the capacity for a linear sensing response with a correlation coefficient of R2 ~ 0.992 over a wide sensing range. In our study, we also developed an IDC temperature sensor that is based on the capacitance variation principle as the IDC sensing element is heated. We compared the performance of the proposed temperature-sensing systems with different fiber-optic temperature sensors (which are based on the fiber-optic wavelength shift method, the long grating fiber-optic Sagnac loop, and probe type fiber-optics) in terms of sensitivity, dynamic range, and linearity. We observed that the proposed sensing systems have better sensing performance than the above mentioned sensing system. PMID- 27409621 TI - Stair-Walking Performance in Adolescents with Intellectual Disabilities. AB - Most individuals with intellectual disabilities (ID) demonstrate problems in learning and movement coordination. Consequently, they usually have difficulties in activities such as standing, walking, and stair climbing. To monitor the physical impairments of these children, regular gross motor evaluation is crucial. Straight-line level walking is the most frequently used test of their mobility. However, numerous studies have found that unless the children have multiple disabilities, no significant differences can be found between the children with ID and typically-developed children in this test. Stair climbing presents more challenges than level walking because it is associated with numerous physical factors, including lower extremity strength, cardiopulmonary endurance, vision, balance, and fear of falling. Limited ability in those factors is one of the most vital markers for children with ID. In this paper, we propose a sensor-based approach for measuring stair-walking performance, both upstairs and downstairs, for adolescents with ID. Particularly, we address the problem of sensor calibration to ensure measurement accuracy. In total, 62 participants aged 15 to 21 years, namely 32 typically-developed (TD) adolescents, 20 adolescents with ID, and 10 adolescents with multiple disabilities (MD), participated. The experimental results showed that stair-walking is more sensitive than straight line level walking in capturing gait characteristics for adolescents with ID. PMID- 27409622 TI - A Novel Wearable Device for Food Intake and Physical Activity Recognition. AB - Presence of speech and motion artifacts has been shown to impact the performance of wearable sensor systems used for automatic detection of food intake. This work presents a novel wearable device which can detect food intake even when the user is physically active and/or talking. The device consists of a piezoelectric strain sensor placed on the temporalis muscle, an accelerometer, and a data acquisition module connected to the temple of eyeglasses. Data from 10 participants was collected while they performed activities including quiet sitting, talking, eating while sitting, eating while walking, and walking. Piezoelectric strain sensor and accelerometer signals were divided into non overlapping epochs of 3 s; four features were computed for each signal. To differentiate between eating and not eating, as well as between sedentary postures and physical activity, two multiclass classification approaches are presented. The first approach used a single classifier with sensor fusion and the second approach used two-stage classification. The best results were achieved when two separate linear support vector machine (SVM) classifiers were trained for food intake and activity detection, and their results were combined using a decision tree (two-stage classification) to determine the final class. This approach resulted in an average F1-score of 99.85% and area under the curve (AUC) of 0.99 for multiclass classification. With its ability to differentiate between food intake and activity level, this device may potentially be used for tracking both energy intake and energy expenditure. PMID- 27409623 TI - Internet of Things: A Review of Surveys Based on Context Aware Intelligent Services. AB - The Internet of Things (IoT) has made it possible for devices around the world to acquire information and store it, in order to be able to use it at a later stage. However, this potential opportunity is often not exploited because of the excessively big interval between the data collection and the capability to process and analyse it. In this paper, we review the current IoT technologies, approaches and models in order to discover what challenges need to be met to make more sense of data. The main goal of this paper is to review the surveys related to IoT in order to provide well integrated and context aware intelligent services for IoT. Moreover, we present a state-of-the-art of IoT from the context aware perspective that allows the integration of IoT and social networks in the emerging Social Internet of Things (SIoT) term. PMID- 27409624 TI - TRPM8 Puts the Chill on Prostate Cancer. AB - Prostate cancer (PCa) is one of the most frequently diagnosed cancers in developed countries. Several studies suggest that variations in calcium homeostasis are involved in carcinogenesis. Interestingly, (Transient Receptor Potential Melastatin member 8) TRPM8 calcium permeable channel expression is differentially regulated during prostate carcinogenesis, thereby suggesting a potential functional role for this channel in those cell processes, which are important for PCa evolution. Indeed, several studies have shown that TRPM8 plays a key role in processes such as the proliferation, viability and cell migration of PCa cells. Where cell migration is concerned, TRPM8 seems to have a protective anti-invasive effect and could be a particularly promising therapeutic target. The goal of this review is to inventory advances in understanding of the role of TRPM8 in the installation and progression of PCa. PMID- 27409625 TI - Environmental Health Related Socio-Spatial Inequalities: Identifying "Hotspots" of Environmental Burdens and Social Vulnerability. AB - Differential exposure to multiple environmental burdens and benefits and their distribution across a population with varying vulnerability can contribute heavily to health inequalities. Particularly relevant are areas with high cumulative burdens and high social vulnerability termed as "hotspots". This paper develops an index-based approach to assess these multiple burdens and benefits in combination with vulnerability factors at detailed intra-urban level. The method is applied to the city of Dortmund, Germany. Using non-spatial and spatial methods we assessed inequalities and identified "hotspot" areas in the city. We found modest inequalities burdening higher vulnerable groups in Dortmund (CI = 0.020 at p < 0.05). At the detailed intra-urban level, however, inequalities showed strong geographical patterns. Large numbers of "hotspots" exist in the northern part of the city compared to the southern part. A holistic assessment, particularly at a detailed local level, considering both environmental burdens and benefits and their distribution across the population with the different vulnerability, is essential to inform environmental justice debates and to mobilize local stakeholders. Locating "hotspot" areas at this detailed spatial level can serve as a basis to develop interventions that target vulnerable groups to ensure a health conducive equal environment. PMID- 27409626 TI - Assessing a New Method for Measuring Fetal Exposure to Mercury: Newborn Bloodspots. AB - BACKGROUND: Measuring mercury in newborn bloodspots to determine fetal exposures is a novel methodology with many advantages. Questions remain, however, about its reliability as an estimate of newborn exposure to mercury. METHODS: We studied mercury concentrations in paired bloodspots and cord blood from a convenience sample of 48 Minnesota women and infants. RESULTS: The limit of detection for bloodspots was higher than for cord blood (0.7 and 0.3 MUg/L in bloodspots and cord blood, respectively) with the result that mercury was detected in only 38% of newborn bloodspots compared to 62% of cord blood samples. The geometric mean mercury concentration in cord blood was 0.6 MUg/L. Mercury concentrations were almost uniformly lower in bloodspots than in cord blood (mean ratio (+/-SD) = 0.85 +/- 0.4), their mean value was significantly less than that for the cord blood (p = 0.02), and the two methods were highly correlated (r = 0.82). CONCLUSION: These preliminary findings indicate that newborn bloodspot mercury measurements have utility; however, until bloodspot analyses are more sensitive, they are likely to underestimate in utero exposure. PMID- 27409627 TI - A Community-Based Study of Quality of Life and Depression among Older Adults. AB - The goal of the study was to assess the quality of life (QOL) and depression and provide further insights into the relationship between QOL and depression among community-dwelling elderly Chinese people. Baseline data were collected from 1168 older adults (aged >= 60) in a large, prospective cohort study on measurement and evaluation of health-promoting and health-protecting behaviors intervention on chronic disease in different community-dwelling age groups. QOL was assessed using the 26-item, World Health Organization Quality of Life, brief version (WHOQOL-BREF) and depression was assessed using the 30-item Geriatric Depression Scale (GDS). The mean WHOQOL-BREF score for all dimensions was approximately 60, with the highest mean value (61.92) observed for social relationships, followed by environment, physical health, and psychological health domains. In this cohort, 26.1% of elderly urban adults met GDS criteria for depression. There were negative correlations between physical health (Odds Ratio (OR) = 0.928, 95% Confidence Interval (CI): 0.910-0.946), psychological health (OR = 0.906, 95% CI: 0.879-0.934), environment (OR = 0.966, 95% CI: 0.944-0.989) and depression among elderly people. Those with depression were older, less educated, had a lower monthly income, and were more likely to report insomnia. All WHOQOL-BREF domains, with the exception of the social domain were negatively correlated with depression. PMID- 27409628 TI - Air Quality and Health Impacts of Future Ethanol Production and Use in Sao Paulo State, Brazil. AB - It is often argued that liquid biofuels are cleaner than fossil fuels, and therefore better for human health, however, the evidence on this issue is still unclear. Brazil's high uptake of ethanol and role as a major producer makes it the most appropriate case study to assess the merits of different biofuel policies. Accordingly, we modeled the impact on air quality and health of two future fuel scenarios in Sao Paulo State: a business-as-usual scenario where ethanol production and use proceeds according to government predictions and a counterfactual scenario where ethanol is frozen at 2010 levels and future transport fuel demand is met with gasoline. The population-weighted exposure to fine particulate matter (PM2.5) and ozone was 3.0 MUg/m3 and 0.3 ppb lower, respectively, in 2020 in the scenario emphasizing gasoline compared with the business-as-usual (ethanol) scenario. The lower exposure to both pollutants in the gasoline scenario would result in the population living 1100 additional life years in the first year, and if sustained, would increase to 40,000 life-years in year 20 and continue to rise. Without additional measures to limit emissions, increasing the use of ethanol in Brazil could lead to higher air pollution related population health burdens when compared to policy that prioritizes gasoline. PMID- 27409629 TI - Health Impact Assessment of Air Pollution in Sao Paulo, Brazil. AB - Epidemiological research suggests that air pollution may cause chronic diseases, as well as exacerbation of related pathologies such as cardiovascular and respiratory morbidity and mortality. This study evaluates air pollution scenarios considering a Health Impact Assessment approach in Sao Paulo, Brazil. We have analyzed abatement scenarios of Particulate Matter (PM) with an aerodynamic diameter <10 MUm (PM10), <2.5 MUm (PM2.5) and ozone concentrations and the health effects on respiratory and cardiovascular morbidity and mortality in the period from 2009 to 2011 through the APHEKOM tool, as well as the associated health costs. Considering World Health Organization (WHO) standards of PM2.5 (10 MUg/m3), Sao Paulo would avoid more than 5012 premature deaths (equivalent to 266,486 life years' gain) and save US$15.1 billion annually. If Sao Paulo could even diminish the mean of PM2.5 by 5 MUg/m3, nearly 1724 deaths would be avoided, resulting in a gain of US$ 4.96 billion annually. Reduced levels of PM10, PM2.5 and ozone could save lives and an impressive amount of money in a country where economic resources are scarce. Moreover, the reduced levels of air pollution would also lower the demand for hospital care, since hospitalizations would diminish. In this sense, Brazil should urgently adopt WHO air pollution standards in order to improve the quality of life of its population. PMID- 27409630 TI - Heat Shock Enhances the Expression of the Human T Cell Leukemia Virus Type-I (HTLV-I) Trans-Activator (Tax) Antigen in Human HTLV-I Infected Primary and Cultured T Cells. AB - The environmental factors that lead to the reactivation of human T cell leukemia virus type-1 (HTLV-I) in latently infected T cells in vivo remain unknown. It has been previously shown that heat shock (HS) is a potent inducer of HTLV-I viral protein expression in long-term cultured cell lines. However, the precise HTLV-I protein(s) and mechanisms by which HS induces its effect remain ill-defined. We initiated these studies by first monitoring the levels of the trans-activator (Tax) protein induced by exposure of the HTLV-I infected cell line to HS. HS treatment at 43 degrees C for 30 min for 24 h led to marked increases in the level of Tax antigen expression in all HTLV-I-infected T cell lines tested including a number of HTLV-I-naturally infected T cell lines. HS also increased the expression of functional HTLV-I envelope gp46 antigen, as shown by increased syncytium formation activity. Interestingly, the enhancing effect of HS was partially inhibited by the addition of the heat shock protein 70 (HSP70) inhibitor pifithlin-MU (PFT). In contrast, the HSP 70-inducer zerumbone (ZER) enhanced Tax expression in the absence of HS. These data suggest that HSP 70 is at least partially involved in HS-mediated stimulation of Tax expression. As expected, HS resulted in enhanced expression of the Tax-inducible host antigens, such as CD83 and OX40. Finally, we confirmed that HS enhanced the levels of Tax and gp46 antigen expression in primary human CD4+ T cells isolated from HTLV-I infected humanized NOD/SCID/gammac null (NOG) mice and HTLV-I carriers. In summary, the data presented herein indicate that HS is one of the environmental factors involved in the reactivation of HTLV-I in vivo via enhanced Tax expression, which may favor HTLV-I expansion in vivo. PMID- 27409633 TI - Increasing Plant Based Foods or Dairy Foods Differentially Affects Nutrient Intakes: Dietary Scenarios Using NHANES 2007-2010. AB - Diets rich in plant foods and lower in animal-based products have garnered increased attention among researchers, dietitians and health professionals in recent years for their potential to, not only improve health, but also to lessen the environmental impact. However, the potential effects of increasing plant based foods at the expense of animal-based foods on macro- and micronutrient nutrient adequacy in the U.S. diet is unknown. In addition, dairy foods are consistently under consumed, thus the impact of increased dairy on nutrient adequacy is important to measure. Accordingly, the objective of this study was to use national survey data to model three different dietary scenarios to assess the effects of increasing plant-based foods or dairy foods on macronutrient intake and nutrient adequacy. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 for persons two years and older (n = 17,387) were used in all the analyses. Comparisons were made of usual intake of macronutrients and shortfall nutrients of three dietary scenarios that increased intakes by 100%: (i) plant-based foods; (ii) protein-rich plant-based foods (i.e., legumes, nuts, seeds, soy); and (iii) milk, cheese and yogurt. Scenarios (i) and (ii) had commensurate reductions in animal product intake. In both children (2-18 years) and adults (>=19 years), the percent not meeting the Estimated Average Requirement (EAR) decreased for vitamin C, magnesium, vitamin E, folate and iron when plant-based foods were increased. However the percent not meeting the EAR increased for calcium, protein, vitamin A, and vitamin D in this scenario. Doubling protein-rich plant-based foods had no effect on nutrient intake because they were consumed in very low quantities in the baseline diet. The dairy model reduced the percent not meeting the EAR for calcium, vitamin A, vitamin D, magnesium, and protein, while sodium and saturated fat levels increased. Our modeling shows that increasing plant-based foods could lead to unintended dietary outcomes without simultaneous changes in the types and amounts of plant foods currently consumed. Increasing dairy foods, which are currently under-consumed, could assist in improving the intakes of many nutrients of concern. PMID- 27409631 TI - Food Habits, Lifestyle Factors, and Risk of Prostate Cancer in Central Argentina: A Case Control Study Involving Self-Motivated Health Behavior Modifications after Diagnosis. AB - Cancer is the second most important non-communicable disease worldwide and disproportionately impacts low- to middle-income countries. Diet in combination with other lifestyle habits seems to modify the risk for some cancers but little is known about South Americans. Food habits of Argentinean men pre- and post diagnosis of prostate cancer (n = 326) were assessed along with other lifestyle factors. We studied whether any of the behaviors and risk factors for prostate cancer were found in men with other cancers (n = 394), compared with control subjects (n = 629). Before diagnosis, both cases reported a greater mean consumption of meats and fats and lower intakes of fruits, green vegetables, cruciferous vegetables, legumes, nuts, seeds, and whole grains than the controls (all p < 0.001). After diagnosis, cases significantly reduced the intake of meats and fats, and reported other dietary modifications with increased consumption of fish, fruits (including red fruits in prostate cancer), cruciferous vegetables, legumes, nuts, and black tea (all p < 0.001). Additional lifestyle aspects significantly predominant in cases included a reduced quality of sleep, emotional stress, low physical activity, tobacco smoking, alcohol consumption, living in rural areas, and being exposed to environmental contaminants. Argentinian men were predisposed to modify their unhealthy dietary habits and other lifestyle factors after cancer diagnosis. PMID- 27409632 TI - Preventive Effects of Fermented Brown Rice and Rice Bran against Prostate Carcinogenesis in TRAP Rats. AB - Fermented brown rice and rice bran with Aspergillus oryzae (FBRA) is considered to have the potential to prevent chemically-induced carcinogenesis in multiple organs of rodents. In the present study, we evaluated the possible chemopreventive effects of FBRA against prostate tumorigenesis. Six-week-old male rats of the transgenic rat for adenocarcinoma of prostate (TRAP) strain were fed diets containing 5% or 10% FBRA for 15 weeks. Animals were sacrificed at 21 weeks of age, and the ventral and lateral prostate were removed for histopathological evaluation and immunoblot analyses. FBRA decreased the incidence of adenocarcinoma in the lateral prostate and suppressed the progression of prostate carcinogenesis. Treatment with FBRA induced apoptosis and inhibited cell proliferation in histologically high-grade prostatic intraepithelial neoplasias. Phospho-AMP-activated kinase alpha (Thr172) was up-regulated in the prostate of rats fed the diet supplemented with FBRA. These results indicate that FBRA controls tumor growth by activating pathways responsive to energy deprivation and suggest that FBRA has translational potential for the prevention of human prostate cancer. PMID- 27409634 TI - Relationships of Dietary Histidine and Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study. AB - Our previous studies have demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women and high-fat diet-induced obese rats. However, the effects of dietary histidine on general population are not known. The objective of this Internet-based cross sectional study was to evaluate the associations between dietary histidine and prevalence of overweight/obesity and abdominal obesity in northern Chinese population. A total of 2376 participants were randomly recruited and asked to finish our Internet-based dietary questionnaire for the Chinese (IDQC). Afterwards, 88 overweight/obese participants were randomly selected to explore the possible mechanism. Compared with healthy controls, dietary histidine was significantly lower in overweight (p < 0.05) and obese (p < 0.01) participants of both sexes. Dietary histidine was inversely associated with body mass index (BMI), waist circumference (WC) and blood pressure in overall population and stronger associations were observed in women and overweight/obese participants. Higher dietary histidine was associated with lower prevalence of overweight/obesity and abdominal obesity, especially in women. Further studies indicated that higher dietary histidine was associated with lower fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), 2-h postprandial glucose (2 h-PG), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C-reactive protein (CRP), malonaldehyde (MDA) and vaspin and higher glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and adiponectin of overweight/obese individuals of both sexes. In conclusion, higher dietary histidine is inversely associated with energy intake, status of insulin resistance, inflammation and oxidative stress in overweight/obese participants and lower prevalence of overweight/obesity in northern Chinese adults. PMID- 27409635 TI - Avenanthramides Prevent Osteoblast and Osteocyte Apoptosis and Induce Osteoclast Apoptosis in Vitro in an Nrf2-Independent Manner. AB - Oats contain unique bioactive compounds known as avenanthramides (AVAs) with antioxidant properties. AVAs might enhance the endogenous antioxidant cellular response by activation of the transcription factor Nrf2. Accumulation of reactive oxygen species plays a critical role in many chronic and degenerative diseases, including osteoporosis. In this disease, there is an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts, which is accompanied by increased osteoblast/osteocyte apoptosis and decreased osteoclast apoptosis. We investigated the ability of the synthethic AVAs 2c, 2f and 2p, to 1-regulate gene expression in bone cells, 2-affect the viability of osteoblasts, osteocytes and osteoclasts, and the generation of osteoclasts from their precursors, and 3 examine the potential involvement of the transcription factor Nrf2 in these actions. All doses of AVA 2c and 1 and 5 uM dose of 2p up-regulated collagen 1A expression. Lower doses of AVAs up-regulated OPG (osteoprotegerin) in OB-6 osteoblastic cells, whereas 100 MUM dose of 2f and all concentrations of 2c down regulated RANKL gene expression in MLO-Y4 osteocytic cells. AVAs did not affect apoptosis of OB-6 osteoblastic cells or MLO-Y4 osteocytic cells; however, they prevented apoptosis induced by the DNA topoisomerase inhibitor etoposide, the glucocorticoid dexamethasone, and hydrogen peroxide. AVAs prevented apoptosis of both wild type (WT) and Nrf2 Knockout (KO) osteoblasts, demonstrating that AVAs induced survival does not require Nrf2 expression. Further, KO osteoclast precursors produced more mature osteoclasts than WT; and KO cultures exhibited less apoptotic osteoclasts than WT cultures. Although AVAs did not affect WT osteoclasts, AVA 2p reversed the low apoptosis of KO osteoclasts. These in vitro results demonstrate that AVAs regulate, in part, the function of osteoblasts and osteocytes and prevent osteoblast/osteocyte apoptosis and increase osteoclast apoptosis; further, these regulatory actions are independent of Nrf2. PMID- 27409637 TI - Respiratory Effects of Sarafotoxins from the Venom of Different Atractaspis Genus Snake Species. AB - Sarafotoxins (SRTX) are endothelin-like peptides extracted from the venom of snakes belonging to the Atractaspididae family. A recent in vivo study on anesthetized and ventilated animals showed that sarafotoxin-b (SRTX-b), extracted from the venom of Atractaspis engaddensis, decreases cardiac output by inducing left ventricular dysfunction while sarafotoxin-m (SRTX-m), extracted from the venom of Atractaspis microlepidota microlepidota, induces right ventricular dysfunction with increased airway pressure. The aim of the present experimental study was to compare the respiratory effects of SRTX-m and SRTX-b. Male Wistar rats were anesthetized, tracheotomized and mechanically ventilated. They received either a 1 LD50 IV bolus of SRTX-b (n = 5) or 1 LD50 of SRTX-m (n = 5). The low frequency forced oscillation technique was used to measure respiratory impedance. Airway resistance (Raw), parenchymal damping (G) and elastance (H) were determined from impedance data, before and 5 min after SRTX injection. SRTX-m and SRTX-b injections induced acute hypoxia and metabolic acidosis with an increased anion gap. Both toxins markedly increased Raw, G and H, but with a much greater effect of SRTX-b on H, which may have been due to pulmonary edema in addition to bronchoconstriction. Therefore, despite their structural analogy, these two toxins exert different effects on respiratory function. These results emphasize the role of the C-terminal extension in the in vivo effect of these toxins. PMID- 27409638 TI - Antisense-Based Progerin Downregulation in HGPS-Like Patients' Cells. AB - Progeroid laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS, OMIM #176670), are premature and accelerated aging diseases caused by defects in nuclear A-type Lamins. Most HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type Lamins. This mutation activates a cryptic splice site leading to the deletion of 50 amino acids at its carboxy terminal domain, resulting in a truncated and permanently farnesylated Prelamin A called Prelamin A Delta50 or Progerin. Some patients carry other LMNA mutations affecting exon 11 splicing and are named "HGPS-like" patients. They also produce Progerin and/or other truncated Prelamin A isoforms (Delta35 and Delta90) at the transcriptional and/or protein level. The results we present show that morpholino antisense oligonucleotides (AON) prevent pathogenic LMNA splicing, markedly reducing the accumulation of Progerin and/or other truncated Prelamin A isoforms (Prelamin A Delta35, Prelamin A Delta90) in HGPS-like patients' cells. Finally, a patient affected with Mandibuloacral Dysplasia type B (MAD-B, carrying a homozygous mutation in ZMPSTE24, encoding an enzyme involved in Prelamin A maturation, leading to accumulation of wild type farnesylated Prelamin A), was also included in this study. These results provide preclinical proof of principle for the use of a personalized antisense approach in HGPS-like and MAD-B patients, who may therefore be eligible for inclusion in a therapeutic trial based on this approach, together with classical HGPS patients. PMID- 27409636 TI - Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways. AB - Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation and/or by directly mediating cell death, all through the toxin activity upon degradation of antitoxin. Intensive study has revealed specific details of TA module functions, but significant gaps remain about the molecular details of activation via antitoxin degradation used by different bacteria and in different environments. This review summarizes the current state of knowledge about the interaction of antitoxins with cellular proteases Lon and ClpP to mediate TA module activation. An understanding of these processes can answer long-standing questions regarding stochastic versus specific activation of TA modules and provide insight into the potential for manipulation of TA modules to alter bacterial growth. PMID- 27409639 TI - Long Noncoding RNA and mRNA Expression Profiles in the Thyroid Gland of Two Phenotypically Extreme Pig Breeds Using Ribo-Zero RNA Sequencing. AB - The thyroid gland is an important endocrine organ modulating development, growth, and metabolism, mainly by controlling the synthesis and secretion of thyroid hormones (THs). However, little is known about the pig thyroid transcriptome. Long non-coding RNAs (lncRNAs) regulate gene expression and play critical roles in many cellular processes. Yorkshire pigs have a higher growth rate but lower fat deposition than that of Jinhua pigs, and thus, these species are ideal models for studying growth and lipid metabolism. This study revealed higher levels of THs in the serum of Yorkshire pigs than in the serum of Jinhua pigs. By using Ribo-zero RNA sequencing-which can capture both polyA and non-polyA transcripts the thyroid transcriptome of both breeds were analyzed and 22,435 known mRNAs were found to be expressed in the pig thyroid. In addition, 1189 novel mRNAs and 1018 candidate lncRNA transcripts were detected. Multiple TH-synthesis-related genes were identified among the 455 differentially-expressed known mRNAs, 37 novel mRNAs, and 52 lncRNA transcripts. Bioinformatics analysis revealed that differentially-expressed genes were enriched in the microtubule-based process, which contributes to THs secretion. Moreover, integrating analysis predicted 13 potential lncRNA-mRNA gene pairs. These data expanded the repertoire of porcine lncRNAs and mRNAs and contribute to understanding the possible molecular mechanisms involved in animal growth and lipid metabolism. PMID- 27409641 TI - Electrochemical Potential Gradient as a Quantitative in Vitro Test Platform for Cellular Oxidative Stress. AB - Oxidative stress in a biological system is often defined as a redox imbalance within cells or groups of cells within an organism. Reductive-oxidative (redox) imbalances in cellular systems have been implicated in several diseases, such as cancer. To better understand the redox environment within cellular systems, it is important to be able to characterize the relationship between the intensity of the oxidative environment, characterized by redox potential, and the biomolecular consequences of oxidative damage. In this study, we show that an in situ electrochemical potential gradient can serve as a tool to simulate exogenous oxidative stress in surface-attached mammalian cells. A culture plate design, which permits direct imaging and analysis of the cell viability, following exposure to a range of solution redox potentials, was developed. The in vitro oxidative stress test vessel consists of a cell growth flask fitted with two platinum electrodes that support a direct current along the flask bottom. The applied potential span and gradient slope can be controlled by adjusting the constant current magnitude across the vessel with spatially localized media potentials measured with a sliding reference electrode. For example, the viability of Chinese Hamster Ovary cells under a gradient of redox potentials indicated that cell death was initiated at approximately 0.4 V vs. standard hydrogen electrode (SHE) media potential and this potential could be modified with antioxidants. This experimental platform may facilitate studies of oxidative stress characteristics on different types of cells by enabling imaging live cell cultures that have been exposed to a gradient of exogenous redox potentials. PMID- 27409640 TI - Virulence Studies of Different Sequence Types and Geographical Origins of Streptococcus suis Serotype 2 in a Mouse Model of Infection. AB - Multilocus sequence typing previously identified three predominant sequence types (STs) of Streptococcus suis serotype 2: ST1 strains predominate in Eurasia while North American (NA) strains are generally ST25 and ST28. However, ST25/ST28 and ST1 strains have also been isolated in Asia and NA, respectively. Using a well standardized mouse model of infection, the virulence of strains belonging to different STs and different geographical origins was evaluated. Results demonstrated that although a certain tendency may be observed, S. suis serotype 2 virulence is difficult to predict based on ST and geographical origin alone; strains belonging to the same ST presented important differences of virulence and did not always correlate with origin. The only exception appears to be NA ST28 strains, which were generally less virulent in both systemic and central nervous system (CNS) infection models. Persistent and high levels of bacteremia accompanied by elevated CNS inflammation are required to cause meningitis. Although widely used, in vitro tests such as phagocytosis and killing assays require further standardization in order to be used as predictive tests for evaluating virulence of strains. The use of strains other than archetypal strains has increased our knowledge and understanding of the S. suis serotype 2 population dynamics. PMID- 27409643 TI - Comparison of ProSeal laryngeal mask airway (PLMA) with cuffed and uncuffed endotracheal tubes in infants. AB - We aimed to compare cuffed and uncuffed endotracheal tubes (ETTs) with ProSealTM laryngeal mask airway (PLMA) in terms of airway security and extubation, starting out from the hypothesis that PLMA will provide alternative airway safety to the endotracheal tubes, and that airway complications will be less observed. After obtaining approval from the local Ethics Committee and parental informed consent, 120 pediatric patients 1-24 months old, American Society of Anesthesiologists physical status I-II, requiring general anesthesia for elective lower abdominal surgery, were randomized into PLMA (Group P, n = 40), cuffed ETT (Group C, n = 40), and uncuffed ETT (Group UC, n = 40) groups. The number of intubation or PLMA insertion attempts was recorded. Each patient's epigastrium was auscultated for gastric insufflation, leak volumes and air leak fractions (leak volume/inspiratory volume) were recorded. Post-operative adverse events related to airway management were also followed up during the first post-operative hour. Demographic and surgical data were similar among the groups. There were significantly fewer airway manipulations in the Group P than in the other groups (p < 0.01), and leak volume and air leak fractions were greater in the Group UC than in the other two groups (p < 0.01). Laryngospasm was significantly lower in the Group P during extubation and within the first minute of post-extubation than in the other groups (p < 0.01). Based on this study, PLMA may be a good alternative to cuffed and uncuffed ETTs for airway management of infants due to the ease of manipulation and lower incidence of laryngospasm. PMID- 27409644 TI - Pregnancy Suppresses the Daily Rhythmicity of Core Body Temperature and Adipose Metabolic Gene Expression in the Mouse. AB - Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesized that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy-induced changes in clock gene expression. Gonadal adipose tissue and plasma were collected from C57BL/6J mice before and on days 6, 10, 14, and 18 of pregnancy (term 19 d) at 4 hour intervals across a 24-hour period. Adipose expression of clock genes and downstream metabolic genes were determined by quantitative RT-PCR, and Tc was measured by intraperitoneal temperature loggers. Adipose clock gene expression showed robust rhythmicity throughout pregnancy, but absolute levels varied substantially across gestation. Rhythmic expression of the metabolic genes Lipe, Pnpla2, and Lpl was clearly evident before pregnancy; however, this rhythmicity was lost with the onset of pregnancy. Tc rhythm was significantly altered by pregnancy, with a 65% decrease in amplitude by term and a 0.61 degrees C decrease in mesor between days 6 and 18. These changes in Tc, however, did not appear to be linked to adipose clock gene expression across pregnancy. Overall, our data show marked adaptations in the adipose clock in pregnancy, with an apparent decoupling of adipose clock and lipolytic/lipogenic gene rhythms from early in gestation. PMID- 27409642 TI - Mucin-Type O-Glycosylation in Gastric Carcinogenesis. AB - Mucin-type O-glycosylation plays a crucial role in several physiological and pathological processes of the gastric tissue. Modifications in enzymes responsible for key glycosylation steps and the consequent abnormal biosynthesis and expression of their glycan products constitute well-established molecular hallmarks of disease state. This review addresses the major role played by mucins and associated O-glycan structures in Helicobacter pylori adhesion to the gastric mucosa and the subsequent establishment of a chronic infection, with concomitant drastic alterations of the gastric epithelium glycophenotype. Furthermore, alterations of mucin expression pattern and glycan signatures occurring in preneoplastic lesions and in gastric carcinoma are also described, as well as their impact throughout the gastric carcinogenesis cascade and in cancer progression. Altogether, mucin-type O-glycosylation alterations may represent promising biomarkers with potential screening and prognostic applications, as well as predictors of cancer patients' response to therapy. PMID- 27409645 TI - Evaluation of Immortalized AVPV- and Arcuate-Specific Neuronal Kisspeptin Cell Lines to Elucidate Potential Mechanisms of Estrogen Responsiveness and Temporal Gene Expression in Females. AB - In females, ovarian estradiol modulates kisspeptin (Kiss-1) synthesis to act as an obligatory regulator of downstream gonadotropin release in vivo, via stimulation of GnRH neurons. Changes in the ovarian condition are relayed to the neuroendocrine hypothalamus via two sexually dimorphic Kiss-1 populations, located in the anteroventral periventricular (AVPV) and arcuate nuclei, conveying estradiol-positive and -negative feedback, respectively. To elucidate how differential responsiveness to estradiol is mediated in these populations, we generated two kisspeptin-secreting cell lines from an adult kiss1-green fluorescent protein (GFP) female mouse. These lines recapitulate in vivo responsiveness to estradiol, with KTaV-3 (AVPV) cells demonstrating significantly increased kiss1 expression under high physiological estradiol exposure, whereas KTaR-1 (arcuate) cells exhibit kiss1 suppression after lower estradiol exposure. Baseline expression of estrogen receptor-alpha (esr1) differs significantly between KTaV-3 and KTaR-1 cells, with KTaR-1 cells demonstrating higher basal expression of esr1. Estradiol stimulation of kiss1 expression in KTaV-3 cells is modulated in a dose-dependent manner up to 25.0 pM, with less responsiveness observed at higher doses (>50.0 pM). In contrast, KTaR-1 kiss1 attenuates at lower estradiol doses (2.0-5.0 pM), returning to baseline levels at 25.0 pM and greater. Furthermore, the expression of the core clock genes bmal1 and per2 show normal rhythms in KTaV-3 cells, regardless of estradiol treatment. Conversely, KTaR-1 antiphasic transcription of bmal1 and per2 is phase delayed by low estradiol treatment. Strikingly, estradiol induces circadian rhythms of kiss1 expression only in KTaV-3 cells. Further exploration into estradiol responsiveness will reveal mechanisms responsible for the differential expression pattern demonstrated in vivo between these cell types. PMID- 27409647 TI - Expanding Porencephalic Cysts: Prenatal Imaging and Differential Diagnosis. AB - OBJECTIVES: The aim of this study was to report the prenatal imaging findings of expanding porencephalic cyst, which have not been previously described in the prenatal period, and to underline that these lesions can involve the cerebellum and not exclusively the supratentorial structures. MATERIALS AND METHODS: This is a retrospective observational study of five cases with a prenatal diagnosis of expanding porencephalic cyst. RESULTS: The cystic lesion was located in the supra and infratentorial space in 2 cases, respectively, or in both in one case. The lesion expanded into the pericerebral space or communicated with the ventricular system in 4 and 1 cases, respectively. Differential diagnosis included tumoural lesion in 2 cases because of internal echogenic components related to haemorrhagic changes, which were identified using foetal MRI, and arachnoid cyst in 2 cases because of expansion into the pericerebral space. In the last case, communication within the ventricular system mimicked a unilateral ventriculomegaly. CONCLUSION: Differential diagnosis of any cystic lesion with extra-axial component should include expanding porencephalic cyst. Foetal MRI is helpful to differentiate this entity from extra-axial lesions such as arachnoid cysts but also from rare tumours. PMID- 27409648 TI - Changes in fruit, vegetable and juice consumption after the diagnosis of type 2 diabetes: a prospective study in men. AB - Given the importance of prevention of complications in type 2 diabetes (T2D), we aimed to examine changes over time in consumption of fruits, vegetables and juice among men who were diagnosed with T2D in comparison with men without diabetes. The prospective Cohort of Swedish Men, aged 45-79 years in 1997, was used to examine changes in diet after diagnosis of T2D. Dietary intake was assessed using FFQ in 1997 and 2009. In all, 23 953 men who were diabetes free at baseline (1997) and completed both FFQ were eligible to participate in the study. Diagnosis of T2D was reported by subjects and ascertained through registers. Multivariable linear mixed models were used to examine changes in mean servings/week over time. In total, 1741 men developed T2D during the study period. Increased consumption of vegetables and fruits was observed among those who developed T2D (equivalent to 1.6 servings/week, 95 % CI 1.08, 2.03) and men who remained diabetes free (0.7 servings/week, 95 % CI 0.54, 0.84). Consumption of juice decreased by 0.6 servings/week (95 % CI -0.71, -0.39) among those who developed T2D and increased by 0.1 servings/week (95 % CI 0.05, 0.15) in those who were diabetes free. Changes over time and between groups were statistically significant. Although improvements in diet were observed, only 36 % of those with T2D and 35 % of those without diabetes consumed >=5 servings of fruits and vegetables/d in 2009. PMID- 27409649 TI - The Brazilian orthodontic storm. PMID- 27409646 TI - Minireview: Lymphangioleiomyomatosis (LAM): The "Other" Steroid-Sensitive Cancer. AB - Lymphangioleiomyomatosis (LAM) is a devastating rare lung disease affecting primarily childbearing age women in which tumors consisting of abnormal smooth muscle-like cells grow within the lungs and progressively lead to loss of pulmonary function. LAM cells metastasize to the lungs, predominantly through the lymphatics; however, the source of the LAM cell is still unknown. LAM cells contain inactivating mutations in genes encoding tuberous sclerosis 1 or 2, proteins that normally limit cell growth through suppression of mammalian target of rapamycin complex 1. As of today, sirolimus (an mammalian target of rapamycin complex 1 inhibitor) is the only treatment, available for LAM patients that is approved by the Food and Drug Administration; however, this drug and others in its class provide stabilization but not remission of LAM. One of the biggest problems in treating LAM is that both the origin of the LAM cells and the mechanism of the sexual dimorphism in LAM are still not understood. LAM cells express estrogen and progesterone receptors, and lung function declines during periods of high circulating estrogen levels. Moreover, numerous basic research studies find that estrogen is a key driving force in LAM cell proliferation, migration, and metastasis. In this review, we highlight recent insights regarding the role of steroid hormones in LAM and discuss possible explanations for the profound female sexual dimorphism of LAM. PMID- 27409650 TI - Gingival recession: its causes and types, and the importance of orthodontic treatment. AB - Gingival recession has direct causes and predisposing factors. Orthodontic treatment is able to prevent recession and even contribute to its treatment, with or without periodontal approach, depending on the type and severity of gingival tissue damage. There is no evidence on the fact that orthodontic treatment alone might induce gingival recession, although it might lead the affected teeth (usually mandibular incisors or maxillary canines) to be involved in situations that act as predisposing factors, allowing direct causes to act and, therefore, trigger recession, especially when the buccal bone plate is very thin or presents with dehiscence. Several aspects regarding the relationship between orthodontic treatment and gingival recession have been addressed, and so has the importance of the periosteum to the mechanism of gingival recession formation. Clinical as well as experimental trials on the subject would help to clarify this matter, of which understanding is not very deep in the related literature. PMID- 27409651 TI - An interview with Roberto Lima Filho. PMID- 27409652 TI - Association between oronasopharyngeal abnormalities and malocclusion in Northeastern Brazilian preschoolers. AB - OBJECTIVE: Evidence is contradictory regarding the association between oronasopharyngeal abnormalities and malocclusion. The aim of the present study was to assess the association between oronasopharyngeal abnormalities and malocclusion (anterior open bite and posterior crossbite) in preschoolers. METHODS: A cross-sectional study was conducted with a representative sample of 732 preschoolers aged 3-5 years old selected randomly from private and public preschools. Anterior open bite (AOB) and posterior crossbite (PC) were evaluated through a clinical exam. Parents/caregivers answered a questionnaire addressing sociodemographic indicators and oronasopharyngeal issues. Statistical analysis involved descriptive analysis and Poisson regression (p < 0.05). RESULTS: The prevalences of AOB and PC were 21.0% and 11.6%, respectively. Being three years old (PR = 1.244; 95% CI = 1.110-1.394; p < 0.001), being four years old (PR = 1.144; 95% CI = 1.110 - 1.394; p = 0.015), absence of allergy (PR = 1.158; 95% CI = 1.057 - 1.269; p = 0.002), not having undergone nose surgery (PR = 1.152; 95% CI = 1.041 - 1.275; p = 0.006) and having a sore throat more than five times in the same year (PR = 1.118; 95% CI = 1.011 - 1.237; p = 0.030) were significantly associated with AOB. The absence of asthma (PR = 1.082; 95% CI = 1.012 - 1.156; p = 0.020), not having undergone throat surgery (PR = 1.112; 95% CI = 1.068 - 1.158; p < 0.001) and not having undergone nose surgery (PR = 1.114; 95% CI = 1.069 - 1.160; p < 0.001) remained associated with PC. CONCLUSION: Significant associations were found between oronasopharyngeal-reported abnormalities and the presence of AOB and PC in preschoolers. PMID- 27409653 TI - Superelasticity and force plateau of nickel-titanium springs: an in vitro study. AB - OBJECTIVE: This paper analyzed whether nickel-titanium closed coil springs (NTCCS) have a different superelastic (SE) behavior according to activation and whether their force plateau corresponds to that informed by the manufacturer. METHODS: A total of 160 springs were divided into 16 subgroups according to their features and activated proportionally to the length of the extensible part (NiTi) of the spring (Y). The force values measured were analyzed to determine SE rates and force plateaus, which were mathematically calculated. These plateaus were compared to those informed by the manufacturer. Analysis of variance was accomplished followed by Tukey post-hoc test to detect and analyze differences between groups. RESULTS: All subgroups were SE at the activation of 400% of Y length, except for: subgroups 4B and 3A, which were SE at 300%; subgroups 4E and 4G, which were SE at 500%; and subgroup 3C, which was SE at 600%. Subgroup 3B did not show a SE behavior. Force plateaus depended on activation and, in some subgroups and some activations, were similar to the force informed. CONCLUSIONS: Most of the springs showed SE behavior at 400% of activation. Force plateaus are difficult to compare due to lack of information provided by manufacturers. PMID- 27409654 TI - Efficiency of two protocols for maxillary molar intrusion with mini-implants. AB - OBJECTIVE: The aim of this study was to compare the efficiency of two protocols for maxillary molar intrusion with two or three mini-implants. METHODS: Twenty five maxillary first molars extruded for loss of their antagonists in adult subjects were selected. The sample was divided into two groups, according to the intrusion protocol with two or three mini-implants. Group 1 consisted of 15 molars that were intruded by two mini-implants. Group 2 consisted of 10 molars intruded by three mini-implants. Changes with treatment were analyzed in lateral cephalograms at the beginning and at the end of intrusion of maxillary molars. RESULTS: Results showed that there was no difference in efficiency for the two intrusion protocols. It was concluded that extruded maxillary molars can be intruded with two or three mini-implants with similar efficiency. PMID- 27409655 TI - Validity of the Psychosocial Impact of Dental Aesthetics Questionnaire for use on Brazilian adolescents. AB - INTRODUCTION: The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) is a multi-item psychometric instrument used to assess patients' perspective of the impact specifically related to Orthodontics. The cross-culturally adapted Brazilian version of the PIDAQ has demonstrated good reliability, validity and acceptability. OBJECTIVE: The aim of the present study was to test the validity and reliability of the Brazilian version of the PIDAQ for use among adolescents aged between 11 and 14 years old. METHODS: Having established the possibility of maintaining the operational characteristics of the Brazilian version of PIDAQ for the target age group, 194 individuals in the city of Belo Horizonte, Brazil, completed the questionnaire. The subjects were examined for the presence/absence of malocclusion based on the criteria of the Dental Aesthetic Index (DAI) to test discriminant validity. Internal consistency was measured by means of Cronbach's alpha coefficient which ranged from 0.59 to 0.86 for the subscales. Test-retest reliability was assessed by means of intraclass correlation coefficient which ranged from 0.54 to 0.89 for aesthetic concern and psychological impact. RESULTS: Discriminant validity revealed that subjects without malocclusion had different PIDAQ scores in comparison to those with malocclusion. CONCLUSION: These findings suggest that the Brazilian version of PIDAQ for adolescents has satisfactory psychometric properties and is applicable to this age group in Brazil. PMID- 27409656 TI - Cephalometric evaluation of the effects of the Twin Block appliance in subjects with Class II, Division 1 malocclusion amongst different cervical vertebral maturation stages. AB - OBJECTIVES: To evaluate the cephalometric changes in skeletal, dentoalveolar and soft tissue variables induced by Clark's Twin Block (CTB) in Class II, Division 1 malocclusion patients and to compare these changes in different cervical vertebral maturation stages. METHODS: Pre- and post-treatment/observation lateral cephalograms of 53 Class II, Division 1 malocclusion patients and 60 controls were compared to evaluate skeletal, dentoalveolar and soft tissue changes. Skeletal maturity was assessed according to cervical vertebral maturation stages. Pre- and post-treatment/observation mean changes and differences (T2-T1) were compared by means of Wilcoxon sign rank and Mann-Whitney U-tests, respectively. Intergroup comparisons between different cervical stages were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (p <= 0.05) . RESULTS: When compared with controls, there was a significant reduction in ANB angle (p < 0.001), which was due to a change in SNB angle in CS-2 and CS-3 (p < 0.001), and in SNA (p < 0.001) and SNB (p = 0.016) angles in the CS-4 group. There was significant increase in the GoGn-SN angle in CS-2 (p = 0.007) and CS-4 (p = 0.024), and increase in Co-Gn and Go-Gn amongst all cervical stages (p < 0.05). There was significant decrease in U1-SN and increase in IMPA amongst all cervical stages (p < 0.05). There was significant retraction of the upper lip in CS-3 (p = 0.001), protrusion of the lower lip in CS-2 (p = 0.005), increase in nasolabial angle in CS-4 (p = 0.006) and Z-angle in CS-3 (p = 0.016), reduction in H-angle in CS-2 (p = 0.013) and CS-3 (p = 0.002) groups. When pre- and post-treatment mean differences were compared between different cervical stages, significant differences were found for SNA, SNB and UI-SN angles and overjet. . CONCLUSIONS: The Twin-Block along with the normal craniofacial growth improves facial esthetics in Class II, Division 1 malocclusion by changes in underlying skeletal and dentoalveolar structures. The favorable mandibular growth occurs during any of the cervical vertebral maturation stages, with more pronounced effect during CS-3 stage. PMID- 27409657 TI - Bilateral en-masse distalization of maxillary posterior teeth with skeletal anchorage: a case report. AB - OBJECTIVE: The aim of this study was to introduce a new method for bilateral distal movement of the entire maxillary posterior segment. CASE REPORT: A 17-year old girl with Class I skeletal malocclusion (end-to-end molar relationships, deviated midline and space deficiency for left maxillary canine) was referred for orthodontic treatment. She did not accept maxillary first premolars extraction. A modified Hyrax appliance (Dentaurum Ispringen, Germany) was used for bilateral distalization of maxillary posterior teeth simultaneously. Expansion vector was set anteroposteriorly. Posterior legs of Hyrax were welded to first maxillary molar bands. All posterior teeth on each side consolidated with a segment of 0.017 * 0.025-in stainless steel wire from the buccal side. Anterior legs of Hyrax were bent into eyelet form and attached to the anterior palate with two mini-screws (2 * 10 mm) (Jeil Medical Corporation Seoul, South Korea). Hyrax opening rate was 0.8 mm per month. Lateral cephalometric radiographs were used to evaluate the extent of distal movement. 3.5-mm distalization of posterior maxillary teeth was achieved in five months. RESULTS: A nearly bodily distal movement without anchorage loss was obtained. CONCLUSION: The mini-screw supported modified Hyrax appliance was found to be helpful for achieving en-masse distal movement of maxillary posterior teeth. PMID- 27409659 TI - Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern. AB - This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as one of the requirements to become diplomate by the BBO. PMID- 27409658 TI - Class II malocclusion with accentuated occlusal plane inclination corrected with miniplate: a case report. AB - INTRODUCTION: A canted occlusal plane presents an unesthetic element of the smile. The correction of this asymmetry has been typically considered difficult by orthodontists, as it requires complex mechanics and may sometimes even require orthognathic surgery. OBJECTIVE: This paper outlines the case of a 29-year-old woman with Class II malocclusion, pronounced midline deviation and accentuated occlusal plane inclination caused by mandibular deciduous molar ankylosis. METHODS: The patient was treated with a miniplate used to provide anchorage in order to intrude maxillary teeth and extrude mandibular teeth on one side, thus eliminating asymmetry. Class II was corrected on the left side by means of distalization, anchored in the miniplate as well. On the right side, maxillary first premolar was extracted and molar relationship was kept in Class II, while canines were moved to Class I relationship. The patient received implant prosthetic rehabilitation for maxillary left lateral incisor and mandibular left second premolar. RESULTS: At the end of treatment, Class II was corrected, midlines were matched and the canted occlusal plane was totally corrected, thereby improving smile function and esthetics. PMID- 27409660 TI - Improving gingival smile by means of guided bone regeneration principles. AB - OBJECTIVE: This study evaluated the effectiveness of guided bone regeneration (GBR) carried out with xenogenic bone substitute (Bio-OssTM) and collagen resorbable membrane (Bio-GideTM) to improve gingival smile (GS) in patients with excessive vertical maxillary growth (EVMG). METHODS: Twelve healthy women aged between 20 and 49 years old (mean age of 26 years), with 5 mm or more of gingival exposure during fully posed smile (FPS) due to EVMG, were included. Baseline digital photographs were taken with standardized head position at rest and FPS. In eight out of 12 cases, crown lengthening procedure was indicated and the initial incision was made 2 to 4 mm from the gingival margin. In four cases, with no indication for crown lengthening procedure, a sulcular incision was performed. GBR was performed in all cases, using micro screws and/or titanium mesh associated with Bio-OssTM and Bio-GideTM. After 10 days, sutures were removed. Recall appointments were scheduled at 1, 6, and 12 months when standardized photographs were again taken. ImageToolTM software was used to measure the gingival exposure (GE) during FPS from the standardized close-up smile photographs at baseline and 12 months. RESULTS: GE mean at baseline was 275.44 mm2. After 12 months, patients who undergone exclusively GBR procedure, presented GE reduction of 40.7%, ? = 112.01 mm2 (statistically significant, p = 0.12), and patients who had crown lengthening associated with the graft had a reduction of 60%, ? = 167.01 mm2. CONCLUSION: Our results using GBR to improve GS in cases of EVMG showed an exceptionally high patient acceptance and satisfaction. One-year follow-up confirmed stable results. PMID- 27409661 TI - Promoter Identification and Transcription Analysis of Penicillin-Binding Protein Genes in Streptococcus pneumoniae R6. AB - Penicillin-binding proteins (PBPs) are membrane-associated enzymes, which are involved in the last two steps of peptidoglycan biosynthesis, and some of them are key players in cell division. Furthermore, they are targets of beta-lactams, the most widely used antibiotics. Nevertheless, very little is known about the expression and regulation of PBP genes. Using transcriptional mapping, we now determined the promoter regions of PBP genes from the laboratory strain Streptococcus pneumoniae R6 and examined the expression profile of these six promoters. The extended -10 region is highly conserved and complies with a sigma(A)-type promoter consensus sequence. In contrast, the -35 region is poorly conserved, indicating the possibility for differential PBP regulation. All PBP promoters were constitutively expressed and highly active during the exponential and early stationary growth phase. However, the individual expression of PBP promoters varied approximately fourfold, with pbp1a being the highest and pbp3 the lowest. Furthermore, the deletion of one nucleotide in the spacer region of the PBP3 promoter reduced pbp3 expression ~10-fold. The addition of cefotaxime above the minimal inhibitory concentration (MIC) did not affect PBP expression in the penicillin-sensitive R6 strain. No evidence for regulation of S. pneumoniae PBP genes was obtained. PMID- 27409663 TI - Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization. AB - Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or beta-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs-induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs-up regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells. PMID- 27409664 TI - The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelial-mesenchymal transition in breast cancer. AB - Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPR-Cas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant p53 which acts as a 'molecular switch' between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53-mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis. PMID- 27409665 TI - Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer. AB - The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1-1.52, p = 0.001; Iota2 = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88-2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC. PMID- 27409666 TI - CCL2/CCR2 axis is associated with postoperative survival and recurrence of patients with non-metastatic clear-cell renal cell carcinoma. AB - PURPOSE: Chemokine (C-Cmotif) ligand 2 (CCL2) is a major chemokine that recruit monocytes and macrophages to the sites of inflammation. Recent researches have clarified that overexpression of CCL2 is associated with unfavorable prognosis in various cancer types. In this study, we aim to determine the prognostic value of CCL2 expression as well as its receptor C-C motif receptor type 2 (CCR2) in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) after surgery. RESULTS: Both high CCL2 and CCR2 expression were remarkably correlated with shortened survival time (P < 0.001 and P < 0.001, respectively) and increased risk of recurrence (P = 0.001 and P = 0.003, respectively). The combination of CCL2 and CCR2 expression (CCL2/CCR2 signature) could offer a better prognostic stratification. Furthermore, multivariate analyses identified CCL2/CCR2 signature as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) (P = 0.007 and P = 0.043, respectively). The incorporation of CCL2/CCR2 signature would refine individual risk stratification and predictive accuracy of the well-established models. MATERIALS AND METHODS: We retrospectively examined the intratumoral expression of CCL2 and CCR2 by immunohistochemical staining in 268 histologically proven non-metastatic ccRCC patients receiving surgery in a single institution between 2001 and 2004. Kaplan Meier analysis and Cox regression were applied to determine the prognostic value of CCL2 and CCR2 expression. Concordance index was calculated to compare predictive accuracy of the established models. CONCLUSIONS: Combined CCL2 and CCR2 expression emerges as an independent prognostic factor for non-metastatic ccRCC patients after surgical treatment. PMID- 27409667 TI - SUMOylation of PES1 upregulates its stability and function via inhibiting its ubiquitination. AB - PES1 is a component of the PeBoW complex, which is required for the maturation of 28S and 5.8S ribosomal RNAs, as well as for the formation of the 60S ribosome. Deregulation of ribosomal biogenesis can contribute to carcinogenesis. In this study, we showed that PES1 could be modified by the small ubiquitin-like modifier (SUMO) SUMO-1, SUMO-2 and SUMO-3, and SUMOylation of PES1 was stimulated by estrogen (E2). One major SUMOylation site (K517) was identified in the C-terminal Glu-rich domain of PES1. Substitution of K517 with arginine abolished the SUMOylation of PES1. SUMOylation also stabilized PES1 through inhibiting its ubiquitination. In addition, PES1 SUMOylation positively regulated the estrogen signaling pathway. SUMOylation enhanced the ability of PES1 to promote estrogen receptor alpha (ERalpha)-mediated transcription by increasing the stability of ERalpha, both in the presence and absence of E2. Moreover, SUMOylation of PES1 also increased the proportion of S-phase cells in the cell cycle and promoted the proliferation of breast cancer cells both in vitro and in vivo. These findings showed that posttranslational modification of PES1 by SUMOylation may serve as a key factor that regulates the function of PES1 in vivo. PMID- 27409669 TI - sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS. AB - Colorectal cancer (CRC) is aggressive and associated with TLR4-MD-2 signaling. Toll-like receptor 4 (TLR4) and myeloid differentiation protein 2 (MD-2) were highly expressed in human CRC. The soluble form of extracellular TLR4 domain (sTLR4) and MD-2 may have important roles in binding lipopolysaccharide (LPS). In this study, sTLR4 and MD-2 protein and prepared sTLR4/MD-2 complex were synthesized successfully to restrain LPS-TLR4/MD-2 activation by competing with cellular membrane TLR4 for binding LPS. The sTLR4/MD-2 complex can significantly attenuate LPS induced pro-inflammatory and migration cytokine production in vitro and in vivo, and inhibit the effect of LPS on the cell cycle, migration and invasion of human CRC cells in vitro. Administration of sTLR4/MD-2 complex protected mice from tumor both in xenograft and implantation metastasis model. The sTLR4/MD-2 complex treated mice had smaller tumor, less body weight loss and lower expression of inflammatory cytokines. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model was used as an experimental platform to simulate the physiological and pathological processes of cancers associated with chronic intestinal inflammation. AOM/DSS-induced tumors were inhibited in mice treated by sTLR4/MD-2 complex. It is demonstrated in our study that sTLR4/MD 2 complex could inhibit CRC by competing with binding LPS, raising the complex's possibility of a new prevention agent against CRC. PMID- 27409670 TI - Role of alpha7-nicotinic acetylcholine receptor in nicotine-induced invasion and epithelial-to-mesenchymal transition in human non-small cell lung cancer cells. AB - Nicotine via nicotinic acetylcholine receptors (nAChRs) stimulates non-small cell lung cancer (NSCLC) cell invasion and epithelial to mesenchymal transition (EMT) which underpin the cancer metastasis. However, the receptor subtype-dependent effects of nAChRs on NSCLC cell invasion and EMT, and the signaling pathway underlying the effects remain not fully defined. We identified that nicotine induced NSCLC cell invasion, migration, and EMT; the effects were suppressed by pharmacological intervention using alpha7-nAChR selective antagonists or by genetic intervention using alpha7-nAChR knockdown via RNA inference. Meanwhile, nicotine induced activation of MEK/ERK signaling in NSCLC cells; alpha7-nAChR antagonism or MEK/ERK signaling pathway inhibition suppressed NSCLC cell invasion and EMT marker expression. These results indicate that nicotine induces NSCLC cell invasion, migration, and EMT; the effects are mediated by alpha7-nAChRs and involve MEK/ERK signaling pathway. Delineating the effect of nicotine on the NSCLC cell invasion and EMT at receptor subtype level would improve the understanding of cancer biology and offer potentials for the exploitation of selective ligands for the control of the cancer metastasis. PMID- 27409668 TI - Branched multipeptide immunotherapy for glioblastoma using human leukocyte antigen-A*0201-restricted cytotoxic T-lymphocyte epitopes from ERBB2, BIRC5 and CD99. AB - We investigated the use of cytotoxic T-lymphocyte (CTL) epitopes in peptide immunotherapy for glioblastoma. Three peptides (ERBB2, BIRC5 and CD99) were selected based on their peptide-T2 cell binding affinities and combined in a multipeptide cocktail or a branched multipeptide synthesized with mini polyethylene glycol spacers. Dendritic cells (DCs) pulsed with the multipeptide cocktail or branched multipeptide were compared based on their immunophenotype and cytokine secretion. FACS analysis of alpha-type 1 polarized dendritic cells (alphaDC1s) revealed that both groups highly expressed CD80, CD83 and CD86, indicating that both treatments efficiently generated mature alphaDC1s with the expected phenotype. Production of IL-12p70, IL-12p40 and IL-10 also increased upon alphaDC1 maturation in both groups. CTLs stimulated by either alphaDC1 group ("DC-CTLs") included numerous IFN-gamma-secreting cells against T2 cells loaded with the corresponding multipeptides. Large numbers of IFN-gamma-secreting cells were observed when human glioblastoma cell lines and primary cells were treated with multipeptide-pulsed DC-CTLs. Both multipeptide-pulsed DC-CTL groups exhibited cytotoxic activity of 40-60% against the U251 cell line and 60-80% against primary cells. Branched multipeptide from ERBB2, BIRC5 and CD99 stably bound with T2 cells, and its cytotoxicity toward target cells was similar to that of the multipeptide cocktail. Thus, branched multipeptides could be promising candidates for immunotherapeutic glioblastoma treatment. PMID- 27409671 TI - Cetuximab response in CRC patient-derived xenografts seems predicted by an expression based RAS pathway signature. AB - Cetuximab is an approved treatment for metastatic colorectal carcinoma (mCRC) with codon 12/13-KRAS mutations, recently questioned for its validity, and alternative mutation-based biomarkers were proposed. We set out to investigate whether an expression signature can also predict response by utilizing a cetuximab mouse clinical trial (MCT) dataset on a cohort of 25 randomly selected EGFR+ CRC patient-derived xenografts (PDXs). While we found that the expression of EGFR and its ligands are not predictive of the cetuximab response, we tested a published RAS pathway signature, a 147-gene expression signature proposed to describe RAS pathway activity, against this MCT dataset. Interestingly, our study showed that the observed cetuximab activity has a strong correlation with the RAS pathway signature score, which was also demonstrated to have a certain degree of correlation with a historic clinical dataset. Altogether, the independent validations in unrelated datasets from independent cohort of CRCs strongly suggest that RAS pathway signature may be a relevant expression signature predictive of CRC response to cetuximab. Our data seem to suggest that an mRNA expressing signature may also be developed as a predictive biomarker for drug response, similarly to genetic mutations. PMID- 27409673 TI - AIM2 inhibits autophagy and IFN-beta production during M. bovis infection. AB - Mycobacteria can trigger the AIM2 inflammasome, autophagy activation and type-I interferon release, which are both activated by cytosolic DNA. We have recently demonstrated that activation of the AIM2 inflammasome during M. bovis infection is the result of mycobacterial translocation into the cytosol. To elucidate the effects of inflammasome activation on autophagy, we investigated the role of the AIM2 inflammasome from macrophages infected with a virulent strain of M. bovis. The results showed that the M. bovis-induced AIM2 inflammasome activation decreases autophagy in immortalized and primary murine macrophages. This relied on the inflammasome sensor AIM2 which conjugates with cytosolic DNA to inhibit the STING-dependent pathway involved in selective autophagy and interferon-beta release in Mycobacterium-infected macrophages. These results suggest that the AIM2 cytosolic DNA sensor may conjugate competitively with cytosolic M. bovis DNA to restrict M. bovis induced STING-TBK1-dependent autophagy activation and IFN beta secretion. PMID- 27409672 TI - Stress-induced phosphoprotein-1 maintains the stability of JAK2 in cancer cells. AB - Overexpression of stress-induced phosphoprotein 1 (STIP1) - a co-chaperone of heat shock protein (HSP) 70/HSP90 - and activation of the JAK2-STAT3 pathway occur in several tumors. Combined treatment with a HSP90 inhibitor and a JAK2 inhibitor exert synergistic anti-cancer effects. Here, we show that STIP1 stabilizes JAK2 protein in ovarian and endometrial cancer cells. Knock-down of endogenous STIP1 decreased JAK2 and phospho-STAT3 protein levels. The N-terminal fragment of STIP1 interacts with the N-terminus of JAK2, whereas the C-terminal DP2 domain of STIP1 mediates the interaction with HSP90 and STAT3. A peptide fragment in the DP2 domain of STIP1 (peptide 520) disrupted the interaction between STIP1 and HSP90 and induced cell death through JAK2 suppression. In an animal model, treatment with peptide 520 inhibited tumor growth. In summary, STIP1 modulates the function of the HSP90-JAK2-STAT3 complex. Peptide 520 may have therapeutic potential in the treatment of JAK2-overexpressing tumors. PMID- 27409675 TI - Sex-specific metabolic interactions between liver and adipose tissue in MCD diet induced non-alcoholic fatty liver disease. AB - Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease. PMID- 27409676 TI - Sitagliptin and heart failure hospitalization in patients with type 2 diabetes. AB - This study evaluated the risk of heart failure hospitalization in a 1:1 matched pair sample of sitagliptin ever and never users derived from the Taiwan's National Health Insurance. A total of 85,859 ever users and 85,859 never users matched on 8 digits of propensity score were followed for the first event of heart failure hospitalization until December 31, 2011. The treatment effect (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Additionally, adjusted hazard ratios for heart failure were estimated for the baseline characteristics in sitagliptin ever users. Results showed that the incidence of heart failure hospitalization was 1,020.16 and 832.54 per 100,000 person-years, respectively, for ever and never users, with an overall hazard ratio (95% confidence intervals) of 1.262 (1.167-1.364). While compared to never users, the respective hazard ratio for the first, second, and third tertile of cumulative duration < 3.7, 3.7-10.3 and >10.3 months was 2.721 (2.449-3.023), 1.472 (1.318-1.645) and 0.515 (0.447-0.594). Older age, longer diabetes duration, male sex, and use of insulin, sulfonylurea, calcium channel blockers, aspirin, ticlopidine, clopidogrel and dipyridamole were significantly associated with a higher risk in sitagliptin users, but dyslipidemia and use of metformin and statin were protective. In conclusion, sitagliptin increases the risk of heart failure hospitalization within one year of its use, but reduces the risk thereafter. Some factors predisposing to sitagliptin-related heart failure are worthy of attention in clinical practice. PMID- 27409674 TI - Inhibitory effect of thiacremonone on MPTP-induced dopaminergic neurodegeneration through inhibition of p38 activation. AB - Neuroinflammation is implicated for dopaminergic neurodegeneration. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects on several inflammatory disease models. To investigate the protective effect of thiacremonone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment and dopaminergic neurodegeneration, 8 week old ICR mice were given thiacremonone (10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of MPTP (15 mg/kg, four times with 2 h interval) during the last 7 days of treatment. Our data showed that thiacremonone decreased MPTP induced behavioral impairments (Rotarod test, Pole test, and Gait test), dopamine depletion and microglia and astrocytes activations as well as neuroinflammation. Higher activation of p38 was found in the substantia nigra and striatum after MPTP injection, but p38 activation was reduced in thiacremonone treated group. In an in vitro study, thiacremonone (1, 2, and 5 MUg/ml) effectively decreased MPP+ (0.5 mM)-induced glial activation, inflammatory mediators generation and dopaminergic neurodegeneration in cultured astrocytes and microglial BV-2 cells. Moreover, treatment of p38 MAPK inhibitor SB203580 (10 MUM) further inhibited thiacremonone induced reduction of neurodegeneration and neuroinflammation. These results indicated that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and dopaminergic neurodegeneration through inhibition of p38 activation. PMID- 27409678 TI - Small field tritanopia in the peripheral retina. AB - If stimuli are made sufficiently small, color-normal individuals report a loss in hue perception, in particular a decrease in the perception of green, in both the fovea and peripheral retina. This effect is referred to as small field tritanopia. It is not clear, however, how rod input may alter the dynamics of small field tritanopia in the peripheral retina. This paper looks at peripheral hue-naming data obtained for small stimuli at mesopic and photopic retinal illuminances under conditions that minimize (bleach) and maximize (no bleach) rod contribution. The data show that attenuation in the perception of green occurs with larger stimuli in the no-bleach condition than in the bleach condition. As retinal illuminance increases, the stimulus size that elicits small field tritanopia decreases, but the stimulus size is still larger under the no-bleach condition. Small field tritanopia in both the bleach and no-bleach conditions may be related to short-wavelength-sensitive (S) cone activity and its potential role in the mediation of the perception of green. The differences in stimulus size for small field tritanopia may be explained by rod input into the magnocellular and koniocellular pathways, which compromises the strength of the chromatic signals and creates a differential loss in the perception of green as compared to the other elemental hues. PMID- 27409679 TI - Mie scattering of highly focused, scalar fields: an analytic approach. AB - We present a method for modeling the scattering of a focused scalar field incident on a spherical particle. This approach involves the expansion of the incident field in an orthonormal basis of closed-form solutions of the Helmholtz equation which are nonparaxial counterparts of Laguerre-Gaussian beams. This method also allows for the analytic calculation of the forces and torques exerted on a particle at any position with respect to the beam's focus. PMID- 27409680 TI - Introduction to the Maxwell Garnett approximation: tutorial. AB - This tutorial is devoted to the Maxwell Garnett approximation and related theories. Topics covered in this first, introductory part of the tutorial include the Lorentz local field correction, the Clausius-Mossotti relation and its role in the modern numerical technique known as the discrete dipole approximation, the Maxwell Garnett mixing formula for isotropic and anisotropic media, multicomponent mixtures and the Bruggeman equation, the concept of smooth field, and Wiener and Bergman-Milton bounds. PMID- 27409677 TI - Long non-coding RNA BC087858 induces non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT in non-small-cell lung cancer. AB - Our previous study demonstrated that long non-coding RNA (lncRNA) BC087858 could stimulate acquired resistance to EGFR-TKIs in non-small cell lung (NSCLC) but the specific regulatory mechanism remained unknown. We aimed to explore the role and mechanism of lncRNA BC087858 on EGFR-TKIs acquired resistance. LncRNA BC087858 mRNA expression was detected by reverse transcription polymerase chain reaction in different NSCLC cell lines and tissues. The relationship between BC087858 expression and clinicopathological factors was performed by Cox multivariate regression analysis. Small-interfering RNA, flow cytometry and trans-well assay were conducted to explore the biological functions of BC087858. Western blotting was used to analyze the target proteins expression. Over-expression was observed in NSCLC cells and patients with acquired resistance to EGFR-TKIs and significantly associated with a shorter progression-free survival (PFS) (12.0 vs. 17.0 months, P = 0.0217) in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (median PFS 17.6 vs. 12.5 months, P = 0.522) but in patients with non-T790M (median PFS 8.0 vs. 18.25 months,P = 0.0427). Down-regulation of BC087858 could significantly promote PC9/R and PC9/G2 cells invasion (P < 0.05; respectively). BC087858 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the PI3K/AKT and MEK/ERK pathways and epithelial mesenchymal transition (EMT) via up- regulating ZEB1 and Snail. In conclusion, LncRNA BC087858 could promote cells invasion and induce non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT via up- regulating ZEB1 and Snail in NSCLC. PMID- 27409681 TI - Sufficient conditions for the avoidance of spectral dispersion in optical prisms. AB - Prisms are common optical elements consisting of only flat boundary surfaces. Two conditions need to be fulfilled to avoid chromatic aberration for a prism, namely, no mutual image tilt and no mutual image shift for different wavelengths. Mutual image tilt occurs when the unit directional vector of the exit ray varies as a function of the prism's refractive index, resulting in spectral dispersion. In a previous study by the present group [Appl. Opt.45, 3951 (2006)APOPAI0003 693510.1364/AO.45.003951], it was shown that when the rays enter and exit a prism perpendicularly, image reorientation is achieved without spectral dispersion. The present study derives a further sufficient condition to avoid spectral dispersion caused by refraction. The condition explains the ability of Dove prisms and solid glass corner cubes to produce the required image orientation even when the entrance and exit rays are not normal to the respective boundary surfaces. In general, the proposed condition provides a useful analytical guideline for avoiding spectral dispersion in a wide variety of optical systems. PMID- 27409682 TI - Retinal image registration via feature-guided Gaussian mixture model. AB - Registration of retinal images taken at different times, from different perspectives, or with different modalities is a critical prerequisite for the diagnoses and treatments of various eye diseases. This problem can be formulated as registration of two sets of sparse feature points extracted from the given images, and it is typically solved by first creating a set of putative correspondences and then removing the false matches as well as estimating the spatial transformation between the image pairs or solved by estimating the correspondence and transformation jointly involving an iteration process. However, the former strategy suffers from missing true correspondences, and the latter strategy does not make full use of local appearance information, which may be problematic for low-quality retinal images due to a lack of reliable features. In this paper, we propose a feature-guided Gaussian mixture model (GMM) to address these issues. We formulate point registration as the estimation of a feature-guided mixture of densities: A GMM is fitted to one point set, such that both the centers and local features of the Gaussian densities are constrained to coincide with the other point set. The problem is solved under a unified maximum likelihood framework together with an iterative expectation-maximization algorithm initialized by the confident feature correspondences, where the image transformation is modeled by an affine function. Extensive experiments on various retinal images show the robustness of our approach, which consistently outperforms other state-of-the-art methods, especially when the data is badly degraded. PMID- 27409683 TI - Enhancement of Rayleigh scattering in a two-dimensional Fabry-Perot resonator loaded with impurities. AB - We study wave transmission through a Fabry-Perot resonator (FPR) loaded with point-like impurities. We show both analytically in the framework of the coupled mode theory and numerically that there are two different regimes for transmission dependent on the quality of the FPR mirrors. For low quality, we obtain transmittance very similar to the clean FPR with slightly shifted Lorentz peaks. However, for good quality, the transmittance peaks are strongly reduced and substituted with Gaussian peaks because of multiple scattering of waves by each impurity. As a side effect, we observe the angular (channel) conversion in the disordered FPR. We demonstrate that the resonant peaks are dependent on the concentration of impurities to pave a way for resonant measurement of the concentration. PMID- 27409684 TI - Properties of laser speckle images produced from narrow elliptical illumination regions. AB - The properties of laser speckles formed by laser light scattered from narrow elliptical illumination regions on a rough surface are investigated. Analytical expressions are derived for the correlation between 1D pixel data arrays in single speckle images and between averaged pixel data arrays of speckle images from different illumination regions. In deriving the formulas, the phase shift of the scattered light is expressed by a function that approximates the roughness of the illuminated surface. Experimental results are interpreted by the formulas, and the parameters of the formulas are evaluated. PMID- 27409685 TI - Holographic imaging through a scattering medium by diffuser-aided statistical averaging. AB - We introduce a practical digital holographic method capable of imaging through a diffusive or scattering medium. The method relies on statistical averaging from a rotating ground glass diffuser to negate the adverse effects caused by speckle introduced by a static diffuser or scattering medium. In particular, a setup based on Fourier transform holography is used to show that an image can be recovered after scattering by introducing an additional diffuser in the optical setup. This method is capable of recovering object information from behind a scattering layer in biomedical or military imaging applications. PMID- 27409686 TI - Open-geometry Fourier modal method: modeling nanophotonic structures in infinite domains. AB - We present an open-geometry Fourier modal method based on a new combination of open boundary conditions and an efficient k-space discretization. The open boundary of the computational domain is obtained using basis functions that expand the whole space, and the integrals subsequently appearing due to the continuous nature of the radiation modes are handled using a discretization based on nonuniform sampling of the k space. We apply the method to a variety of photonic structures and demonstrate that our method leads to significantly improved convergence with respect to the number of degrees of freedom, which may pave the way for more accurate and efficient modeling of open nanophotonic structures. PMID- 27409687 TI - Invariant quantities of a nondepolarizing Mueller matrix. AB - Orthogonal Mueller matrices can be considered as corresponding either to retarders or to generalized transformations of the polarization basis for the representation of Stokes vectors, so that they constitute the only type of Mueller matrices that preserve the degree of polarization and the intensity of any partially polarized input Stokes vector. The physical quantities that remain invariant when a nondepolarizing Mueller matrix is transformed through its product by different types of orthogonal Mueller matrices are identified and interpreted, providing a better knowledge of the information contained in a nondepolarizing Mueller matrix. PMID- 27409688 TI - Nonrigid registration of remote sensing images via sparse and dense feature matching. AB - In this paper, we propose a novel formulation for building pixelwise alignments between remote sensing images under nonrigid transformation based on matching both sparsely and densely sampled features. Our formulation contains two coupling variables: the nonrigid geometric transformation and the discrete dense flow field. To match sparse features, we fit a geometric transformation specified in a reproducing kernel Hilbert space and impose a locally linear constraint to regularize the transformation. To match dense features, we compute a dense flow field by using a formulation analogous to scale invariant feature transform (SIFT) flow which allows nonrigid matching across different scene appearances. An additional term is introduced to ensure the coherence between the two variables, and we alternatively solve for one variable under the assumption that the other is known. Extensive experiments on both synthetic and real remote sensing images demonstrate that our approach greatly outperforms state-of-the-art methods, particularly when the data contain severe degradations. PMID- 27409689 TI - Polarized light transport in refractive weak scattering media. AB - This paper is devoted to modeling of the light transport in refractive and weak scattering media by means of the vector radiative transfer equation. In refractive media polarization of light depends not only on the law of scattering but also on the refractive index distribution and can change along curved light trajectories according to the Rytov law of the polarization ellipse rotation. Results of numerical simulations are presented in the form of CCD camera images, which is how data are acquired in tomographic imaging experiments. PMID- 27409690 TI - Geometry of the Mueller matrix spectral decomposition. AB - An arbitrary Mueller matrix can be decomposed into a sum of up to four deterministic Mueller-Jones matrices, with strengths given by the eigenvalues of an associated Hermitian matrix. A geometrical representation of the eigenvalues in terms of the matrix invariants, using a barycentric (quaternary) plot, is presented. Different polarization purity measures can be expressed in terms of the barycentric coordinates. PMID- 27409691 TI - Optical trapping force and torque on spheroidal Rayleigh particles with arbitrary spatial orientations. AB - We investigate the spatial orientation dependence of optical trapping forces and intrinsic torques exerted on spheroidal Rayleigh particles under irradiation of highly focused linearly and circularly polarized beams. It is revealed that the maximal trapping forces and torques strongly depend on the orientation of the spheroid, and the spheroidal particle is driven to be stably trapped at the beam focus with its major axis perpendicular to the optical axis. For a linearly polarized trapping beam, the optical torque is always perpendicular to the plane containing the major axis and the polarization direction of the incident beam. Therefore, the spheroid tends to rotate its major axis along with the polarization direction. However, for a circularly polarized trapping beam, the optical torque is always perpendicular to the plane containing the major axis and the optical axis. What is different from the linear polarization case is that the spheroid tends to have the major axis parallel to the projection of the major axis in the transverse plane. The optical torque in the circular polarization case is half of that in the linear polarization case. These optical trapping properties may be exploited in practical optical manipulation, especially for the nonspherical particle's trapping. PMID- 27409692 TI - Quantum polarization fluctuations of an Airy beam in turbulent atmosphere in a slant path. AB - Polarization of light has many applications in quantum information processing, including quantum teleportation and dense coding. In this paper, we investigate the polarization fluctuations of Airy beams propagating in a slant turbulent channel under the "few-photon" limit. Using the quantum Stokes parameters and the quantum degree of polarization, we demonstrate that the degree of polarization of Airy beams increases significantly with the large number of the detection photons, and a higher photon-number level can retain the stability of polarization. Numerical simulations show that the longer propagation distance and the stronger turbulence will lead to less oscillatory behaviors and a decrease in the polarization degree of Airy beams, but a bigger exponential truncation factor will cause an increase in the polarization degree of Airy beams. In contrast with Gaussian beams, the degree of polarization of Airy beams is less affected by atmospheric turbulence and propagation distance under the same conditions, which means that Airy beams possess a resilient ability against turbulence-induced perturbations. These results indicate that Airy beams have great potential for applications in long-distance free-space optical communications to improve the performance of a polarization-encoded free-space quantum communication system. PMID- 27409693 TI - Detection of imprecise estimations for polarization-resolved second-harmonic generation microscopy. AB - Second-harmonic generation microscopy can provide estimation of some local molecule distribution properties. However, in order not to get erroneous conclusions, it is important to detect measurements with insufficient precision. Such a detection technique is developed considering an approximation of the ultimate precision provided by the Cramer-Rao bound. This method is characterized and a simple approximation of its detection and false alarm probabilities is developed. PMID- 27409694 TI - Vector Laguerre-Gauss beams with polarization-orbital angular momentum entanglement in a graded-index medium. AB - It is shown that the vector-vortex Laguerre-Gauss modes with polarization-orbital angular momentum (OAM) entanglement are the vector solutions of the Maxwell equations in a graded-index medium. Focusing of linearly and circularly polarized vortex light beams with nonzero azimuthal and radial indices in a cylindrical graded-index waveguide is investigated. The wave shape variation with distance taking into account the spin-orbit and nonparaxial effects is analyzed. The effect of long-term periodic revival of wave packets due to mode interference in a graded-index cylindrical optical waveguide is demonstrated. High efficiency transfer of a strongly focused spot through an optical waveguide over large distances takes place with a period of revival. PMID- 27409695 TI - Improved estimation of reflectance spectra by utilizing prior knowledge. AB - Estimating spectral reflectance has attracted extensive research efforts in color science and machine learning, motivated through a wide range of applications. In many practical situations, prior knowledge is available that ought to be used. Here, we have developed a general Bayesian method that allows the incorporation of prior knowledge from previous monochromator and spectrophotometer measurements. The approach yields analytical expressions for fast and efficient estimation of spectral reflectance. In addition to point estimates, probability distributions are also obtained, which completely characterize the uncertainty associated with the reconstructed spectrum. We demonstrate that, through the incorporation of prior knowledge, our approach yields improved reconstruction results compared with methods that resort to training data only. Our method is particularly useful when the spectral reflectance to be recovered resides beyond the scope of the training data. PMID- 27409696 TI - Feasibility study for super-resolution 3D integral imaging using time-multiplexed compressive coding. AB - We propose a novel super-resolution 3D II method using a time-multiplexed coding mask for improving the resolution of 3D imaging based on compressive sensing (CS) theory. Instead of sensing raw pixel data, the recording device measures the compressive samples of the observed 3D scene through a coding mask placed in the aerial pickup plane in a 3D II system. With the aid of CS framework, we design an optimum coding mask pattern and use the time-multiplexed scheme to achieve a sequence of low-resolution elemental images (EIs), which contain the subpixel details of the observed 3D scene. The super-resolution EIs array is further recovered by an optimization algorithm. Both computational reconstruction and optical experimental results show the validity of the proposed method. PMID- 27409697 TI - Propagation of polarized waves in inhomogeneous media. AB - A parabolic equation for electromagnetic wave propagation in a random medium is extended to include the depolarization effects in the narrow-angle, forward scattering setting. Closed-form parabolic equations for propagation of the coherence tensor are derived under a Markov approximation model. For a general partially coherent and partially polarized beam wave, this equation can be reduced to a system of ordinary differential equations, allowing a simple numeric solution. An analytical solution exists for statistically homogeneous waves. Estimates based on the perturbation solution support the common knowledge that the depolarization at the optical frequencies is negligible for atmospheric turbulence propagation. These results indicate that the recently published theory [Opt. Lett.40, 3077 (2015)10.1364/OL.40.003077] is not valid for atmospheric turbulence. PMID- 27409698 TI - Propagation of polarized waves in inhomogeneous media: comment. AB - It is argued in J. Opt. Soc. Am. A.33, 1385 (2016) that some of our previous results on the evolution of the polarization state of electromagnetic beams propagating in atmospheric turbulence are not valid and/or our work is not useful. We address such arguments and give clarifications. PMID- 27409699 TI - Stokes-vector and Mueller-matrix polarimetry [Invited]. AB - This paper reviews the current status of instruments for measuring the full 4*1 Stokes vector S, which describes the state of polarization (SOP) of totally or partially polarized light, and the 4*4 Mueller matrix M, which determines how the SOP is transformed as light interacts with a material sample or an optical element or system. The principle of operation of each instrument is briefly explained by using the Stokes-Mueller calculus. The development of fast, automated, imaging, and spectroscopic instruments over the last 50 years has greatly expanded the range of applications of optical polarimetry and ellipsometry in almost every branch of science and technology. Current challenges and future directions of this important branch of optics are also discussed. PMID- 27409700 TI - Accurate radiative transfer calculations for layered media. AB - Simple yet accurate results for radiative transfer in layered media with discontinuous refractive index are obtained by the method of K-integrals. These are certain weighted integrals applied to the angular intensity distribution at the refracting boundaries. The radiative intensity is expressed as the sum of the asymptotic angular intensity distribution valid in the depth of the scattering medium and a transient term valid near the boundary. Integrated boundary equations are obtained, yielding simple linear equations for the intensity coefficients, enabling the angular emission intensity and the diffuse reflectance (albedo) and transmittance of the scattering layer to be calculated without solving the radiative transfer equation directly. Examples are given of half space, slab, interface, and double-layer calculations, and extensions to multilayer systems are indicated. The K-integral method is orders of magnitude more accurate than diffusion theory and can be applied to layered scattering media with a wide range of scattering albedos, with potential applications to biomedical and ocean optics. PMID- 27409701 TI - Scanning Fourier transform spectrometer in the visible range based on birefringent wedges. AB - We introduce a spectrometer capable of measuring sample absorption spectra in the visible regime, based on a time-domain scanning Fourier transform (FT) approach. While infrared FT spectrometers typically employ a Michelson interferometer to create the two delayed light replicas, the proposed apparatus exploits a compact common-mode passive interferometer that relies on the use of birefringent wedges. This ensures excellent path-length stability (~lambda/300) and accuracy, with no need for active feedback or beam tracking. We demonstrate the robustness of the technique measuring the transmission spectrum of a colored bandpass filter over one octave of bandwidth and compare the results with those obtained with a commercial spectrophotometer. PMID- 27409702 TI - Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy. AB - Multiphoton microscopy (MPM) combined with fluorescence lifetime imaging microscopy (FLIM) has enabled three-dimensional quantitative molecular microscopy in vivo. The signal-to-noise ratio (SNR), and thus the imaging rate of MPM-FLIM, which is fundamentally limited by the shot noise and fluorescence saturation, has not been quantitatively studied yet. In this paper, we investigate the SNR performance of the frequency-domain (FD) MPM-FLIM with two figures of merit: the photon economy in the limit of shot noise, and the normalized SNR in the limit of saturation. The theoretical results and Monte Carlo simulations find that two photon FD-FLIM requires 50% fewer photons to achieve the same SNR as conventional one-photon FLIM. We also analytically show that the MPM-FD-FLIM can exploit the DC and higher harmonic components generated by nonlinear optical mixing of the excitation light to improve SNR, reducing the required number of photons by an additional 50%. Finally, the effect of fluorophore saturation on the experimental SNR performance is discussed. PMID- 27409703 TI - Deconvolution methods for structured illumination microscopy. AB - We compare two recently developed multiple-frame deconvolution approaches for the reconstruction of structured illumination microscopy (SIM) data: the pattern illuminated Fourier ptychography algorithm (piFP) and the joint Richardson-Lucy deconvolution (jRL). The quality of the images reconstructed by these methods is compared in terms of the achieved resolution improvement, noise enhancement, and inherent artifacts. Furthermore, we study the issue of object-dependent resolution improvement by considering the modulation transfer functions derived from different types of objects. The performance of the considered methods is tested in experiments and benchmarked with a commercial SIM microscope. We find that the piFP method resolves periodic and isolated structures equally well, whereas the jRL method provides significantly higher resolution for isolated objects compared to periodic ones. Images reconstructed by the piFP and jRL algorithms are comparable to the images reconstructed using the generalized Wiener filter applied in most commercial SIM microscopes. An advantage of the discussed algorithms is that they allow the reconstruction of SIM images acquired under different types of illumination, such as multi-spot or random illumination. PMID- 27409704 TI - Multifluorophore localization as a percolation problem: limits to density and precision. AB - We show that the maximum desirable density of activated fluorophores in a superresolution experiment can be determined by treating the overlapping point spread functions as a problem in percolation theory. We derive a bound on the density of activated fluorophores, taking into account the desired localization accuracy and precision, as well as the number of photons emitted. Our bound on density is close to that reported in experimental work, suggesting that further increases in the density of imaged fluorophores will come at the expense of localization accuracy and precision. PMID- 27409705 TI - Note on the classification of super-resolution in far-field microscopy and information theory. AB - In recent years, several far-field microscopy techniques have been developed which manage to overcome the diffraction limit of resolution. A unifying classification scheme for them is clearly desirable. We argue that existing schemes based on the information capacity of the optical system cannot easily be extended to cover, e.g., stimulated emission depletion microscopy or techniques based on single-molecule imaging. We suggest a classification based on a reconstruction of the Abbe limit. PMID- 27409707 TI - High-numerical-aperture microscopy with a rotating point spread function. AB - Rotating point spread function (PSF) microscopy via spiral phase engineering can localize point sources over large focal depths in a snapshot mode. The present work gives an approximate vector-field analysis of an improved rotating PSF design that encodes both the 3D location and polarization state of a monochromatic point dipole emitter for high-numerical-aperture microscopy. By examining the angle of rotation and the spatial form of the PSF, one can jointly localize point sources and determine the polarization state of light emitted by them over a 3D field in a single snapshot. Results of numerical simulations of noisy data frames under Poisson shot noise conditions and the errors in the recovery of 3D location and dipole orientation for a single point source are discussed. PMID- 27409706 TI - Fisher information theory for parameter estimation in single molecule microscopy: tutorial. AB - Estimation of a parameter of interest from image data represents a task that is commonly carried out in single molecule microscopy data analysis. The determination of the positional coordinates of a molecule from its image, for example, forms the basis of standard applications such as single molecule tracking and localization-based super-resolution image reconstruction. Assuming that the estimator used recovers, on average, the true value of the parameter, its accuracy, or standard deviation, is then at best equal to the square root of the Cramer-Rao lower bound. The Cramer-Rao lower bound can therefore be used as a benchmark in the evaluation of the accuracy of an estimator. Additionally, as its value can be computed and assessed for different experimental settings, it is useful as an experimental design tool. This tutorial demonstrates a mathematical framework that has been specifically developed to calculate the Cramer-Rao lower bound for estimation problems in single molecule microscopy and, more broadly, fluorescence microscopy. The material includes a presentation of the photon detection process that underlies all image data, various image data models that describe images acquired with different detector types, and Fisher information expressions that are necessary for the calculation of the lower bound. Throughout the tutorial, examples involving concrete estimation problems are used to illustrate the effects of various factors on the accuracy of parameter estimation and, more generally, to demonstrate the flexibility of the mathematical framework. PMID- 27409708 TI - Single molecule image formation, reconstruction and processing: introduction. AB - The ability to image at the single molecule scale has revolutionized research in molecular biology. This feature issue presents a collection of articles that provides new insights into the fundamental limits of single molecule imaging and reports novel techniques for image formation and analysis. PMID- 27409709 TI - Rapamycin and rapalogs for tuberous sclerosis complex. AB - BACKGROUND: Previous studies have shown potential benefits of rapamycin or rapalogs for treating people with tuberous sclerosis complex. Although everolimus (a rapalog) is currently approved by the FDA (U.S. Food and Drug Administration) and the EMA (European Medicines Agency) for tuberous sclerosis complex-associated renal angiomyolipoma and subependymal giant cell astrocytoma, applications for other manifestations of tuberous sclerosis complex have not yet been established. A systematic review is necessary to establish the clinical value of rapamycin or rapalogs for various manifestations in tuberous sclerosis complex. OBJECTIVES: To determine the effectiveness of rapamycin or rapalogs in people with tuberous sclerosis complex for decreasing tumour size and other manifestations and to assess the safety of rapamycin or rapalogs in relation to their adverse effects. SEARCH METHODS: Relevant studies were identified by authors from the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and clinicaltrials.gov. Relevant resources were also searched by the authors, such as conference proceedings and abstract books of conferences, from e.g. the Tuberous Sclerosis Complex International Research Conferences, other tuberous sclerosis complex-related conferences and the Human Genome Meeting. We did not restrict the searches by language as long as English translations were available for non English reports.Date of the last searches: 14 March 2016. SELECTION CRITERIA: Randomized or quasi-randomized studies of rapamycin or rapalogs in people with tuberous sclerosis complex. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors using standard acquisition forms. The data collection was verified by one author. The risk of bias of each study was independently assessed by two authors and verified by one author. MAIN RESULTS: Three placebo controlled studies with a total of 263 participants (age range 0.8 to 61 years old, 122 males and 141 females, with variable lengths of study duration) were included in the review. We found high-quality evidence except for response to skin lesions which was judged to be low quality due to the risk of attrition bias. Overall, there are 175 participants in the treatment arm (rapamycin or everolimus) and 88 in the placebo arm. Participants all had tuberous sclerosis complex as proven by consensus diagnostic criteria as a minimum. The quality in the description of the study methods was mixed, although we assessed most domains as having a low risk of bias. Blinding of treatment arms was successfully carried out in all of the studies. However, two studies did not report allocation concealment. Two of the included studies were funded by Novartis Pharmaceuticals.Two studies (235 participants) used oral (systemic) administration of everolimus (rapalog). These studies reported response to tumour size in terms of the number of individuals with a reduction in the total volume of tumours to 50% or more relative to baseline. Significantly more participants in the treatment arm (two studies, 162 participants, high quality evidence) achieved a 50% reduction in renal angiomyolipoma size, risk ratio 24.69 (95% confidence interval 3.51 to 173.41) (P = 0.001). For the sub-ependymal giant cell astrocytoma, our analysis of one study (117 participants, high quality evidence) showed significantly more participants in the treatment arm achieved a 50% reduction in tumour size, risk ratio 27.85 (95% confidence interval 1.74 to 444.82) (P = 0.02). The proportion of participants who showed a skin response from the two included studies analysed was significantly increased in the treatment arms, risk ratio 5.78 (95% confidence interval 2.30 to 14.52) (P = 0.0002) (two studies, 224 participants, high quality evidence). In one study (117 participants), the median change of seizure frequency was -2.9 in 24 hours (95% confidence interval -4.0 to -1.0) in the treatment group versus -4.1 in 24 hour (95% confidence interval -10.9 to 5.8) in the placebo group. In one study, one out of 79 participants in the treatment group versus three of 39 in placebo group had increased blood creatinine levels, while the median percentage change of forced expiratory volume at one second in the treatment arm was -1% compared to 4% in the placebo arm. In one study (117 participants, high quality evidence), we found that those participants who received treatment had a similar risk of experiencing adverse events compared to those who did not, risk ratio 1.07 (95% confidence interval 0.96 - 1.20) (P = 0.24). However, as seen from two studies (235 participants, high quality evidence), the treatment itself led to significantly more adverse events resulting in withdrawal, interruption of treatment, or reduction in dose level, risk ratio 3.14 (95% confidence interval 1.82 to 5.42) (P < 0.0001).One study (28 participants) used topical (skin) administration of rapamycin. This study reported response to skin lesions in terms of participants' perception towards their skin appearance following the treatment. There was a tendency of an improvement in the participants' perception of their skin appearance, although not significant, risk ratio 1.81 (95% confidence interval 0.80 to 4.06, low quality evidence) (P = 0.15). This study reported that there were no serious adverse events related to the study product and there was no detectable systemic absorption of the rapamycin during the study period. AUTHORS' CONCLUSIONS: We found evidence that oral everolimus significantly increased the proportion of people who achieved a 50% reduction in the size of sub-ependymal giant cell astrocytoma and renal angiomyolipoma. Although we were unable to ascertain the relationship between the reported adverse events and the treatment, participants who received treatment had a similar risk of experiencing adverse events as compared to those who did not receive treatment. Nevertheless, the treatment itself significantly increased the risk of having dose reduction, interruption or withdrawal. This supports ongoing clinical applications of oral everolimus for renal angiomyolipoma and subependymal giant cell astrocytoma. Although oral everolimus showed beneficial effect on skin lesions, topical rapamycin only showed a non-significant tendency of improvement. Efficacy on skin lesions should be further established in future research. The beneficial effects of rapamycin or rapalogs on tuberous sclerosis complex should be further studied on other manifestations of the condition. PMID- 27409710 TI - Association of Loss of Independence With Readmission and Death After Discharge in Older Patients After Surgical Procedures. AB - IMPORTANCE: Older adults are at increased risk for adverse events after surgical procedures. Loss of independence (LOI), defined as a decline in function or mobility, increased care needs at home, or discharge to a nonhome destination, is an important patient-centered outcome measure. OBJECTIVE: To evaluate LOI among older adult patients after surgical procedures and examine the association of LOI with readmission and death after discharge in this population. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study examined 9972 patients 65 years and older with known baseline function, mobility, and living situation undergoing inpatient operations from January 2014 to December 2014 at 26 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program Geriatric Surgery Pilot Project. A total of 4895 patients were excluded because they were totally dependent, classified as class 5 by the American Society of Anesthesiologists, undergoing orthopedic or spinal procedures, or died prior to discharge. EXPOSURES: Loss of independence at time of discharge. MAIN OUTCOMES AND MEASURES: Readmission and death after discharge. RESULTS: Of the 5077 patients included in this study, 2736 (53.9%) were female and 3876 (76.3%) were white, with a mean (SD) age of 75 (7) years. For this cohort, LOI increased with age; LOI occurred in 1386 of 2780 patients (49.9%) aged 65 to 74 years, 1162 of 1726 (67.3%) aged 75 to 84 years, and 479 of 571 (83.9%) 85 years and older (P < .001). Readmission occurred in 517 patients (10.2%). In a risk-adjusted model, LOI was strongly associated with readmission (odds ratio, 1.7; 95% CI, 1.4-2.2) and postoperative complication (odds ratio, 6.7; 95% CI, 4.9-9.0). Death after discharge occurred in 69 patients (1.4%). After risk adjustment, LOI was the strongest factor associated with death after discharge (odds ratio, 6.7; 95% CI, 2.4-19.3). Postoperative complication was not significantly associated with death after discharge. CONCLUSIONS AND RELEVANCE: Loss of independence, a patient-centered outcome, was associated with postoperative readmissions and death after discharge. Loss of independence can feasibly be collected across multiple hospitals in a national registry. Clinical initiatives to minimize LOI will be important for improving surgical care for older adults. PMID- 27409711 TI - Dynamics of Inter-DNA Chain Interaction of Photoresponsive DNA. AB - Photoresponsive DNA modified with azobenzene is an attractive design molecule for efficient photoregulation of DNA hybridization, which may be used for controlling DNA functions. Although the essential step of photocontrolling DNA is the initial isomerization of the azobenzene, the dissociation/association kinetics remain unknown. Here, the time-resolved diffusion method was used to trace the dissociation/association processes of photoresponsive DNA. Although the isomerization of azobenzene occurs in picoseconds, the dissociation of the double stranded DNA to single-stranded DNA triggered by the trans to cis isomerization takes place ~10(7) times slower, with a time constant of 670 MUs at 200 MUM. From the concentration dependence, the dissociation and association rates were determined. Furthermore, the reaction rate from the single- to double-stranded DNA after the cis to trans isomerization was measured to be 3.6 ms at 200 MUM. The difference in the melting temperatures of DNA between tethered trans- and cis azobenzene is explained by the different rate of dissociation of the double stranded form. PMID- 27409713 TI - Sterols and Stanols Preserved in Pond Sediments Track Seabird Biovectors in a High Arctic Environment. AB - Seabirds are major vertebrates in the coastal ecosystems of the Canadian High Arctic, where they transport substantial amounts of marine-derived nutrients and pollutants from oceans to land by depositing guano and stomach oils to their nesting area, which often includes nearby freshwater ponds. Here we present novel indicators for evaluating the impact of seabirds on freshwater ecosystems. The ratio of cholesterol/(cholesterol + sitosterol) in pond sediments showed significant enrichment near a nesting colony of northern fulmars (Fulmarus glacialis) and was significantly correlated with ornithogenic enrichment of sediment as determined by sedimentary delta(15)N. The sterol ratio was also correlated with several bioaccumulative persistent organic pollutants (POPs), suggesting its usefulness in tracking biovector enrichment of contaminants. Human derived epicoprostanol was also analyzed in the sediments, and its relationship with an abandoned, prehistoric camp was recorded, suggesting its potential as a tracer of prehistoric human activities in the Arctic. Sterols and stanols preserved in sediments appear to be useful geochemical tools that will inform our understanding of migratory species and the presence of prehistoric human populations in the Arctic, and possibly other animal populations. PMID- 27409714 TI - A Method for the Efficient Fabrication of Multifunctional Mosaic Membranes by Inkjet Printing. AB - Most conventional membrane systems are based on size-selective materials that permeate smaller molecules and retain larger ones. However, membranes that can permeate larger molecules more rapidly than smaller ones could find widespread utilization in multiple arenas of technology. Charge mosaic membranes are one example of such a system. Due to their unique nanostructure, which consists of discrete oppositely charged domains, charge mosaics are capable of permeating large dissolved salts more rapidly than smaller water molecules. Here, we present a combined inkjet printing and template synthesis technique to prepare charge mosaic membranes in a rapid and straightforward manner and demonstrate the unique transport properties that result from the mosaic membrane design. Poly(vinyl alcohol)-based composite inks containing poly(diallyldimethylammonium chloride) or poly(sodium 4-styrenesulfonate) were used to pattern positively charged or negatively charged domains, respectively, on the surface of a polycarbonate track etched membrane with 30 nm pores. The ability to control the net surface charge of the mosaic membranes through the rational deposition of oppositely charged materials was demonstrated and confirmed through nanostructural characterization, electrokinetic measurements, and piezodialysis experiments. Namely, mosaic membranes that possessed an overall neutral charge (i.e., membranes that had equal coverage of positively and negatively charged domains) were capable of enriching the concentration of potassium chloride in the solution that permeated through the membrane. These membranes can be deployed in the many established and emerging nanoscale technologies that rely on the selective transport and separation of ionic solutes from solution. Furthermore, because of the flexibility provided by the membrane fabrication platform, the efforts reported in this work can be extended to other mosaic designs with myriad other functional components. PMID- 27409712 TI - Antimicrobial Graft Copolymer Gels. AB - In view of the growing worldwide rise in microbial resistance, there is considerable interest in designing new antimicrobial copolymers. The aim of the current study was to investigate the relationship between antimicrobial activity and copolymer composition/architecture to gain a better understanding of their mechanism of action. Specifically, the antibacterial activity of several copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and 2 hydroxypropyl methacrylate (HPMA) toward Staphylococcus aureus was examined. Both block and graft copolymers were synthesized using either atom transfer radical polymerization or reversible addition-fragmentation chain transfer polymerization and characterized via (1)H NMR, gel permeation chromatography, rheology, and surface tensiometry. Antimicrobial activity was assessed using a range of well known assays, including direct contact, live/dead staining, and the release of lactate dehydrogenase (LDH), while transmission electron microscopy was used to study the morphology of the bacteria before and after the addition of various copolymers. As expected, PMPC homopolymer was biocompatible but possessed no discernible antimicrobial activity. PMPC-based graft copolymers comprising PHPMA side chains (i.e. PMPC-g-PHPMA) significantly reduced both bacterial growth and viability. In contrast, a PMPC-PHPMA diblock copolymer comprising a PMPC stabilizer block and a hydrophobic core-forming PHPMA block did not exhibit any antimicrobial activity, although it did form a biocompatible worm gel. Surface tensiometry studies and LDH release assays suggest that the PMPC-g-PHPMA graft copolymer exhibits surfactant-like activity. Thus, the observed antimicrobial activity is likely to be the result of the weakly hydrophobic PHPMA chains penetrating (and hence rupturing) the bacterial membrane. PMID- 27409715 TI - Laser-Induced Spallation of Microsphere Monolayers. AB - The detachment of a semiordered monolayer of polystyrene microspheres adhered to an aluminum-coated glass substrate is studied using a laser-induced spallation technique. The microsphere-substrate adhesion force is estimated from substrate surface displacement measurements obtained using optical interferometry, and a rigid-body model that accounts for the inertia of the microspheres. The estimated adhesion force is compared with estimates obtained using an adhesive contact model together with interferometric measurements of the out-of-plane microsphere contact resonance, and with estimated work of adhesion values for the polystyrene aluminum interface. Scanning electron microscope images of detached monolayer regions reveal a unique morphology, namely, partially detached monolayer flakes composed of single hexagonal close packed crystalline domains. This work contributes to the fields of microsphere adhesion and contact dynamics, and demonstrates a unique monolayer delamination morphology. PMID- 27409716 TI - Palladium-Catalyzed 6-Endo Selective Alkyl-Heck Reactions: Access to 5-Phenyl 1,2,3,6-tetrahydropyridine Derivatives. AB - A new type of palladium-catalyzed 6-endo-selective alkyl-Heck reaction of unactivated alkyl iodides has been described. This strategy provides efficient access to a variety of 5-phenyl-1,2,3,6-tetrahydropyridine derivatives, which are important structural motifs for bioactive molecules. This process displays a broad substrate scope with excellent 6-endo selectivity. Mechanistic investigations reveal that this alkyl-Heck reaction performs via a hybrid palladium-radical process. PMID- 27409717 TI - How Similar Are the Disorders Included Under the Umbrella of Obsessive-Compulsive Disorder and Related Disorders? PMID- 27409718 TI - Two's Company, Three's a Crowd: Exciton Localization in Cofacially Arrayed Polyfluorenes. AB - Understanding the mechanisms of long-range energy transfer through polychromophoric assemblies is critically important in photovoltaics and biochemical systems. Using a set of cofacially arrayed polyfluorenes (Fn), we investigate the mechanism of (singlet) exciton delocalization in pi-stacked polychromophoric assemblies. Calculations reveal that effective stabilization of an excimeric state requires an ideal sandwich-like arrangement; yet surprisingly, emission spectroscopy indicates that exciton delocalization is limited to only two fluorene units for all n. Herein, we show that delocalization is determined by the interplay between the energetic gain from delocalization, which quickly saturates beyond two units in larger Fn, and an energetic penalty associated with structural reorganization, which increases linearly with n. With these insights, we propose a hopping mechanism for exciton transfer, based upon the presence of multiple excimeric tautomers of similar energy in larger polyfluorenes (n >= 4) together with the anticipated low thermal barrier of their interconversion. PMID- 27409719 TI - A New Anisotropic Charge-Equilibration Method for Self-Assembly of Organics on Metal Surface: d-Alaninol on Cu(100). AB - The supramolecular chemistry at surfaces has been extensively studied by quantum and classical computational models in order to simulate and reproduce the correct energetics and structures of adsorbed molecules on surfaces at various coverages. We have developed a classical tool able to sample the configuration space overcoming the topological constraints of the standard classical molecular dynamics. Our model is based on the charge equilibration procedure combined with an anisotropic pairwise atomic interaction where an angular dependence, with respect to the metal surface, is explicitly taken into account. The d-alaninol molecule has been chosen as a prototype of a flexible and multifunctional chemical compound which can form manifold complex configurations upon absorption on a metal surface. A detailed analysis of molecular structures and energetics of partial and full coverage has been carried out. The experimental STM image of the monolayer is correctly reproduced by our calculations, indicating that this new approach represents a step forward in the efficient simulation of complex molecular self-assembly. PMID- 27409720 TI - Classics in Chemical Neuroscience: Methylphenidate. AB - As the first drug to see widespread use for the treatment of attention deficit hyperactivity disorder (ADHD), methylphenidate was the forerunner and catalyst to the modern era of rapidly increasing diagnosis, treatment, and medication development for this condition. During its often controversial history, it has variously elucidated the importance of dopamine signaling in memory and attention, provoked concerns about pharmaceutical cognitive enhancement, driven innovation in controlled-release technologies and enantiospecific therapeutics, and stimulated debate about the impact of pharmaceutical sales techniques on the practice of medicine. In this Review, we will illustrate the history and importance of methylphenidate to ADHD treatment and neuroscience in general, as well as provide key information about its synthesis, structure-activity relationship, pharmacological activity, metabolism, manufacturing, FDA-approved indications, and adverse effects. PMID- 27409721 TI - Macular Effects of Silicone Oil Tamponade: Optical Coherence Tomography Findings During and After Silicone Oil Removal. AB - OBJECTIVE: To investigate retinal morphologic changes during silicone oil tamponade and after its removal using spectral domain OCT (SD-OCT) imaging. MATERIALS AND METHODS: Retrospective review of 12 patients who underwent silicone oil tamponade for repair of retinal detachments. Macular OCT scans and volumetric thickness maps were examined qualitatively and quantitatively. RESULTS: Volumetric OCT revealed two distinct patterns during silicone oil: macular thickening (Group A) and macular thinning (Group B). In Group A, mean foveal thickness (507 +/- 169 um vs. 407 +/- 163 um, p = 0.003) and mean macular volume (11.6 +/- 2.4 mm3 vs. 9.9 +/- 1.5 mm3) were significantly increased during tamponade compared to post-oil removal. Group B had significantly decreased mean foveal thickness (210 +/- 38 um vs. 276 +/- 58 um, p = 0.009) and macular volume (7.3 +/- 1.8 mm3 vs. 8.4 +/- 1.8 mm3) during tamponade. Importantly, resolution of macular changes occurred without further intervention and was associated with improved visual acuity in both groups. CONCLUSION: Our series suggests that when faced with unexplained macular edema or macular thinning during tamponade, silicone oil removal alone can achieve resolution of these structural changes. PMID- 27409722 TI - Reply to: Do nasal septal deformities have anything to do with chronic rhinosinusitis? PMID- 27409723 TI - Urethral diverticulectomy with Martius labial fat pad interposition improves symptom resolution and reduces recurrence. AB - OBJECTIVE: To assess the presenting features and medium-term symptomatic outcomes in women having excision of urethral diverticulum with Martius labial fat pad (MLFP) interposition. PATIENTS AND METHODS: We reviewed our prospective database of all female patients having excision of a symptomatic urethral diverticulum between 2007 and 2015. Data on demographics, presenting symptoms and clinical features were collected, as well as postoperative outcomes. RESULTS: In all, 70 women with a mean (range) age of 46.5 (24-77) years underwent excision of urethral diverticulum with MLFP interposition. The commonest presenting symptoms were a urethral mass (69%), urethral pain (61%), and dysuria (57%). Pre-existing stress urinary incontinence (SUI) was present in 41% (29) of the women. After surgery, at a mean (SD) of 18.9 (16.4) months follow-up (median 14 months), complete excision of urethral diverticulum was achieved in all the women, with resolution of urethral mass, dysuria and dyspareunia in all, and urethral pain in 81%. Immediately after surgery, 10 (24%) patients reported de novo SUI, which resolved with time and pelvic floor muscle training such that at 12 months only five (12%) reported continued SUI. There was one symptomatic diverticulum recurrence (1.4%). CONCLUSIONS: The commonest presenting symptom of a female urethral diverticulum is urethral pain followed by dysuria and dyspareunia. Surgical excision with MLFP interposition results in complete resolution of symptoms in most women. The incidence of persistent de novo SUI in an expert high volume centre is 12%. PMID- 27409724 TI - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Mediastinal Staging in a Community Medical Center. AB - RATIONALE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) and positron emission tomography (PET)-computed tomography (CT) are valuable tools for lung cancer staging. Data from tertiary referral centers suggest that these modalities are superior to mediastinoscopy in mediastinal staging. OBJECTIVES: To validate EBUS-TBNA for lung cancer staging in a community center with operators with various levels of experience. METHODS: At an 800-bed community hospital, we reviewed all cases where EBUS-TBNA and PET-CT were performed for mediastinal staging by one of seven private practice pulmonologists. Cases were reviewed with lymph node dissection by mediastinoscopy after negative EBUS-TBNA. MEASUREMENTS AND MAIN RESULTS: Of the 333 cases that were reviewed, 44 underwent mediastinoscopy after negative EBUS-TBNA. Four patients were positive for malignancy at stations 4R and 7 lymph nodes. In none of these cases did EBUS-TBNA reveal lymphoid tissue confirming the sample location. PET-CT showed mediastinal lymph nodes with increased avidity in two of the false-negative cases. EBUS-TBNA plus PET-CT had a sensitivity, specificity, and negative predictive value of 98.86, 100, and 94.87%, respectively, compared with mediastinoscopy for detecting metastasis. CONCLUSIONS: EBUS-TBNA is accurate in detecting mediastinal metastasis of lung cancer in the community setting. PET CT without uptake in lymph nodes reduces the likelihood of malignancy but cannot rule out mediastinal involvement. PMID- 27409726 TI - Melanocytes from the outer root sheath of human hair and epidermal melanocytes display improved melanotic features in the niche provided by cGEL, oligomer-cross linked gelatin-based hydrogel. AB - Non-invasively based cell treatments of depigmented skin disorders are largely limited by means of cell sampling as much as by their routes of application. Human melanocytes cultivated from the outer root sheath of hair follicle (HUMORS) are among the cell types that fit the non-invasive concept by being cultivated out of a minimal sample: hair root. Eventual implementation of HUMORS as a graft essentially depends on a choice of suitable biocompatible, biodegradable carrier that would mechanically and biologically support the cells as transient niche and facilitate their engraftment. Hence, the melanotic features of follicle-derived HUMORS and normal human epidermal melanocytes (NHEM) in engineered scaffolds based on collagen, the usual leading candidate for graft material for a variety of skin transplantation procedures were tested. Hydrogel named cGEL, an enzymatically degraded bovine gelatin chemically cross-linked with an oligomeric copolymer synthesized from pentaerythritol diacrylate monostearate (PEDAS), maleic anhydride (MA), and N-isopropylacrylamide (NiPAAm) or diacetone acrylamide (DAAm), was used. The cGEL provided a friendly three-dimensional (3D) cultivation environment for human melanocytes with increased melanin content of the 3D cultures in comparison to Collagen Cell Carrier(r) (CCC), a commercially available bovine decellularized collagen membrane, and electrospun polycaprolactone (PCL) matrices. One of the cGEL variants fostered not only a dramatic increase in melanin production but also a significant enhancement of melanotic gene PAX3, PMEL, TYR, and MITF expression in comparison to that of both CCC full-length collagen and PCL scaffolds, providing a clearly superior melanocyte niche that may be a suitable candidate for grafting carriers. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3115-3126, 2016. PMID- 27409727 TI - Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy. AB - OBJECTIVES: Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. METHODS: One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. RESULTS: There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4 hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. CONCLUSIONS: Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia. PMID- 27409728 TI - MicroRNA expression profiling of Chinese follicular lymphoma by microarray: A preliminary study. AB - BACKGROUND: MicroRNAs (miRNAs) have been widely regarded as crucial regulators in various biological processes involved in carcinogenesis. However, the comprehensive miRNA profiles of Chinese follicular lymphoma (FL) remains completely unknown. METHODS: The Exiqon miRCURY LNATM microRNA Array (v.18.0) was used to detect the miRNA expression profiles of three Chinese FL samples, and compared to three reactive lymphatic nodes (RLN). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the selected miRNAs in different series. Three databases (miRAnda, miRBase and TargetScan) were used to predict the putative target genes. Bioinformatic analysis (gene ontology analysis and pathway analysis) was performed for further evaluation. RESULTS: The microarray assay demonstrated that 1643 miRNAs were expressed; in which 103 miRNAs were upregulated and 68 miRNAs were downregulated, according to P-value (<0.05) and fold change (FC>2-fold). Furthermore, qRT-PCR was used to confirm that miR-17-5p, miR-20a-5p and miR-19a-3p were upregulated, and miR-3615 was downregulated (P<0.05). Bioinformatic analysis (gene ontology analysis and pathway analysis) was used for further evaluation. Pathway analysis indicated that 25 pathways corresponded to differentially expressed miRNAs (P-value cut-off is 0.05). Furthermore, miR-17-5p, miR-20a-5p and miR-19a-3p were validated by qRT PCR in an independent series including five FL3a and five RLN cases. Data analysis revealed that the changing trend of miR-19a-3p and miR-17-5p expression in the independent series was basically identical with that of the microarray data. CONCLUSIONS: Our results are the first to reveal the miRNA expression profiling of Chinese FL and three upregulated miRNAs. Furthermore, the expression of miR-19a-3p and miR-17-5p were found to be significantly upregulated in FL3a. Further study needs to be urgently performed to reveal its potential role in the pathogenesis of FL in the near future. PMID- 27409729 TI - Breast cancer imaging using radiolabelled somatostatin analogues. AB - Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36-100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22-100%. Furthermore, false negatives and false positives were reported. In the majority of the studies scan outcome was not associated with BC subtype. PMID- 27409731 TI - Coming in postgraduate medicine. PMID- 27409732 TI - Editor's mail. PMID- 27409730 TI - Methods to Characterize the Oligonucleotide Functionalization of Quantum Dots. AB - Currently, DNA nanotechnology offers the most programmable, scalable, and accurate route for the self-assembly of matter with nanometer precision into 1, 2, or 3D structures. One example is DNA origami that is well suited to serve as a molecularly defined "breadboard", and thus, to organize various nanomaterials such as nanoparticles into hybrid systems. Since the controlled assembly of quantum dots (QDs) is of high interest in the field of photonics and other optoelectronic applications, a more detailed view on the functionalization of QDs with oligonucleotides shall be achieved. In this work, four different methods are presented to characterize the functionalization of thiol-capped cadmium telluride QDs with oligonucleotides and for the precise quantification of the number of oligonucleotides bound to the QD surface. This study enables applications requiring the self-assembly of semiconductor-oligonucleotide hybrid materials and proves the conjugation success in a simple and straightforward manner. PMID- 27409733 TI - Problems solutions. PMID- 27409734 TI - What's happening in medicine. PMID- 27409736 TI - Physician-at-large. PMID- 27409735 TI - Washington background. PMID- 27409737 TI - Editorials. PMID- 27409740 TI - Therapeutic Index to Advertisers. PMID- 27409741 TI - Coming in sportsmedicine. PMID- 27409738 TI - Polyuric Syndrome. PMID- 27409744 TI - Names and faces. PMID- 27409742 TI - Letters. PMID- 27409745 TI - Scanning sports. PMID- 27409747 TI - Reagan's Recovery: A Lesson. PMID- 27409746 TI - Running Is Not Enough. PMID- 27409748 TI - Brief reports. PMID- 27409749 TI - The Fitness Facility as a Rehabilitation Care Extender. AB - In brief: Fitness facilities can play an important role in the postacute rehabilitation of injured recreational athletes, especially now that sports medicine practitioners are widely accessible. Such facilities offer special equipment necessary for rehabilitation; their hours suit the recreational athlete's schedule; they can reduce the cost of rehabilitation; and they can help make the injured person the primary agent rather than a passive participant in re habilitation. But patients need supervision by a practitioner to pursue such active rehabilitation safely. The practitioner should know what equipment the patient's health club has and should give him or her detailed instructions for rehabilitative exercises. PMID- 27409750 TI - Characterization of the Patient Population in a Sports Medicine Facility. AB - In brief: This article presents a statistical portrait of the injuries seen over a five-year period at a large sports medicine facility that serves primarily recreational athletes. About half of the 10,271 injuries treated were caused by overuse. Overuse problems exceeded acute injuries in running, tennis, figure skating, and aerobic dance, while acute injuries were more common in skiing, basketball, football, and soccer. The knee was the anatomic area most often injured in all of the major sports. The prevalence of overuse injuries indicates the importance of instructing patients in prevention methods. PMID- 27409751 TI - Inadequate Nutrition and Chronic Calorie Restriction in Adolescent Ballerinas. AB - In brief: Studies show that adult ballerinas practice poor nutrition habits, but little research has been done on adolescent dancers. The authors analyzed the diet composition of 92 female ballet dancers aged 12 to 17 enrolled in six professional schools. Three- day diet histories were used to compile data, and a dietitian worked with the dancers to ensure accuracy in record keeping. The results showed poor nutrition habits and low calorie and nutrition intake. Sixty percent routinely took vitamin or mineral supplements, but not properly. Unfortunately, the dancers' desire to maintain a sylphlike, willowy body makes them unwilling to consume the number of calories required for a healthy diet. A nutrition class in the dance school curriculum would help increase their knowledge and improve their dietary habits. PMID- 27409752 TI - Exertional Headache. AB - In brief: Exertional headache is an acute headache of short duration brought on by some forms of activity. It is usually considered benign. Neurological and radiological studies on a limited number of college students with this complaint failed to reveal any abnormalities. Reducing the stressful activity seems to be beneficial, and a simple prostaglandin inhibitor is currently recommended for relief of pain. Physicians should consider the possibility of preexisting abnormalities in patients whose symptoms persist. PMID- 27409753 TI - Medical Complaints After a Marathon Run in Cool Weather. AB - In brief: Little information is available about medical complaints after marathons held in cool weather. To obtain such information medical records were maintained on every runner requesting medical attention after the Bostonfest Marathon on Oct 30, 1983. One hundred sixty-four (11.5%) of the runners finishing the race requested medical attention at the finish line. Men and women requested attention with equal frequency, but younger (20 to 30 years old) and faster (finishing in less than 3:00) runners sought medical attention more often than the older and slower runners. The complaints and symptoms of runners after the race were similar to those of runners following warm-weather races. PMID- 27409754 TI - A Psychological Study of Health, Injury, and Performance in Athletes on the US Alpine Ski Team. AB - In brief: We assessed life events, depression, and general well-being (health concerns, energy, life satisfaction, cheerfulness, tension, and emotional control) in 73 members of the US Alpine Ski Team. We compared these psychological factors with subsequent surveys of general health, illness, and athletic performance and found that psychological status (especially general well-being) was associated with subsequent health problems, injuries, and performance levels. These findings indicate that coaches and sports medicine specialists must be sensitive to psychological disorders in elite athletes and provide appropriate clinical assessment and treatment. PMID- 27409755 TI - Preventing Overuse Cycling Injuries. AB - In brief: Concurrent with the renaissance in bicycling has come an increase in associated injuries. The most common problem the author sees in his practice is knee pain-usually chondromalacia patellae, patellar tendinitis, or bursitis. The patellofemoral joint is under particular stress in bicycling, and many new recreational riders make two errors: setting the saddle too low and the gears too high. These mistakes cause excessive pressure on the patellofemoral joint. Obtaining the best-fitting bicycle and saddle, adjusting the saddle properly, and using lower gears will help prevent such problems. PMID- 27409756 TI - A Survey of Overuse and Traumatic Hip and Pelvic Injuries in Athletes. AB - In brief: Two hundred and twenty-two hip and pelvic injuries in 204 patients (114 men and 90 women) were retrospectively assessed at a general sports medicine clinic over a two-year period. The three most common bone injuries were sacroiliitis, pelvic and femoral neck stress fractures, and osteitis pubis. The three most common soft-tissue injuries were gluteus medius strain/tendinitis, trochanteric bursitis, and hamstring strain. Running, fitness classes, and racket sports were the most commonly involved activities. Overuse accounted for 82.4% of injuries and trauma 17.6%. Treatment consisted of modified activity, local muscle rehabilitation, physiotherapy, oral anti-inflammatory medication, infrequent corticosteroid injection, orthoses and/or heel lifts, change of footwear, and gradual reintroduction of the specific sport. PMID- 27409757 TI - Instructor Certification: Making Fitness Programs Safer? AB - Certification for fitness instructors-a watchword for safety, reliability, and high standards-has suddenly become the rage in the exercise industry. Unfortunately, it's caveat emptor when shopping for the best instructor; greed and competition inspire shoddy as well as quality training programs. PMID- 27409758 TI - Wheelers Make Strides, All Disabled People Win. AB - Advances in wheelchair design have been spurred by increased interest in wheelchair sports. Those advances have led to high levels of competition for wheelchair athletes plus better opportunities for all disabled people. PMID- 27409759 TI - Abstracts at a glance. PMID- 27409760 TI - Considering the Stationary Cycle. AB - Riding to nowhere on a stationary cycle may be the most boring form of exercise. Nonetheless, it is safe, convenient, and useful in the rehabilitation of some illnesses and injuries. Moreover, a new generation of exercycles sport a variety of "whistles and bells" that may keep users interested. PMID- 27409761 TI - Hyperventilation in Athletes. PMID- 27409764 TI - Massage for Athletes. PMID- 27409762 TI - Snuffing Out the Use of Smokeless Tobacco. AB - Awareness of smokeless tobacco's potential health risks has increased during a period of tremendous popularity for what has been perceived as a safe alternative to smoking. Warning: Smokeless tobacco may be hazardous to your health. PMID- 27409765 TI - Disorganized attachment and risk assessment: A topic for ongoing discussion. PMID- 27409766 TI - Stimuli-Responsive Shape Switching of Polymer Colloids by Temperature-Sensitive Absorption of Solvent. AB - The dynamic manipulation of colloidal particle shape offers a novel design mechanism for the creation of advanced responsive materials. To this end, we introduce a versatile new strategy for shape control of anisotropic polymeric colloidal particles. The concept utilizes temperature-sensitive absorption of a suitable solvent from a binary mixture. Specifically, increasing the temperature in the vicinity of the demixing transition of a binary mixture causes more solvent to be absorbed into the polymeric colloidal particle, which, in turn, lowers the glass transition temperature of the polymer inside the particle, with a concomitant decrease in viscosity. The balance between the internal viscosity and surface tension of the particle is thus disrupted, and the anisotropic shape of the particle shifts to become more spherical. Subsequent rapid temperature quenching can halt the process, leaving the particle with an intermediate anisotropy. The resultant shape anisotropy control provides new routes for studies of the phase transitions of anisotropic colloids and enables the fabrication of unique particles for materials applications. PMID- 27409767 TI - Warning Triggers in Environmental Hazards: Who Should Be Warned to Do What and When? AB - Determining the most effective public warnings to issue during a hazardous environmental event is a complex problem. Three primary questions need to be answered: Who should take protective action? What is the best action? and When should this action be initiated? Warning triggers provide a proactive means for emergency managers to simultaneously answer these questions by recommending that a target group take a specified protective action if a preset environmental trigger condition occurs (e.g., warn a community to evacuate if a wildfire crosses a proximal ridgeline). Triggers are used to warn the public across a wide variety of environmental hazards, and an improved understanding of their nature and role promises to: (1) advance protective action theory by unifying the natural, built, and social themes in hazards research into one framework, (2) reveal important information about emergency managers' risk perception, situational awareness, and threat assessment regarding threat behavior and public response, and (3) advance spatiotemporal models for representing the geography and timing of disaster warning and response (i.e., a coupled natural-built-social system). We provide an overview and research agenda designed to advance our understanding and modeling of warning triggers. PMID- 27409768 TI - Effect of blastocoel fluid reduction before vitrification on gene expression in mouse blastocysts. AB - Artificial collapse of the blastocoel cavity before vitrification can improve the quality of warmed embryos, yet how reduction of blastocoel fluid impacts formation of the blastocyst cell lineages is not clear. The present study assessed the effect of pre-vitrification blastocoel fluid reduction on the survival, hatching rate, and the expression of genes related to apoptosis (Tp53), pluripotency (Pou5f1, Nanog), and differentiation (Cdx2, Eomes, Gata6) in mouse blastocysts. In vivo-produced blastocysts were randomly divided into three groups: The first group was vitrified and warmed; the second group underwent artificial collapse of the blastocoel cavity prior to vitrification and warming; the third group served as the control, in which neither vitrification or artificial collapse was performed. The survival rate of treatment groups was similar to the control group, whereas the hatching rate of artificial collapse/vitrified blastocysts was significantly higher than vitrified blastocysts. Quantitative reverse-transcription PCR analysis revealed a considerable reduction in the expression of Cdx2, Eomes, Gata6, Grb2, and Tp53 transcripts following artificial collapse/vitrification in comparison to the vitrification-alone group; the abundance of Pou5f1 and Nanog, however, did not change. These results suggest that artificial collapse of the blastocoel cavity before vitrification leads to relatively normal expression of apoptosis and development-related genes plus higher hatching rates. Mol. Reprod. Dev. 83: 735 742, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27409770 TI - Functional Promoter Polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and Their Synergism with MMP-7 A-181G in Multiple Sclerosis. AB - Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Matrix metalloproteinases (MMPs) play an important role in breakdown of blood-brain barrier, transmigration, and invasion of immune cells and formation of MS lesions. The aim of present study was to investigate the influence of MMP-2 C-735T and MMP-9 C-1562T variants and their synergism with MMP-7 A-181G on susceptibility to MS. In a case-control study 125 MS patients and 235 healthy individuals from Western Iran were investigated. The various genotypes of MMP-2, MMP-9, and MMP-7 were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In females the presence of MMP-2 C allele was associated with an increased risk of MS (OR = 1.69, p = 0.041). No significant difference was detected between the frequency of MMP-9 T allele in MS patients (8.2%) and controls (12.8%, p = 0.068). The concomitant presence of both MMP-2 C and MMP-7 G alleles was associated with 1.82-fold increased risk of MS (p = 0.002). Also, a synergism was detected between MMP-9 C and MMP-7 G alleles that elevated the risk of MS by 1.5-times (p = 0.035). The presence of haplotype MMP-9 T, MMP-7 G, and MMP-2 C (TGC) compared to haplotype CAG increased the risk of MS by 3.13-fold (p = 0.16). The present study suggests that gene-gene interactions and variants of more genes instead of single gene might play a role in susceptibility to MS. We indicated that synergism between variants of MMP-2, MMP 7, and MMP-9 genes might increase the risk of MS. PMID- 27409771 TI - Alternative Mating Tactics in Male Chameleons (Chamaeleo chamaeleon) Are Evident in Both Long-Term Body Color and Short-Term Courtship Pattern. AB - Alternative mating tactics in males of various taxa are associated with body color, body size, and social status. Chameleons are known for their ability to change body color following immediate environmental or social stimuli. In this study, we examined whether the differential appearance of male common chameleon during the breeding season is indeed an expression of alternative mating tactics. We documented body color of males and used computer vision techniques to classify images of individuals into discrete color patterns associated with seasons, individual characteristics, and social contexts. Our findings revealed no differences in body color and color patterns among males during the non-breeding season. However, during the breeding season males appeared in several color displays, which reflected body size, social status, and behavioral patterns. Furthermore, smaller and younger males resembled the appearance of small females. Consequently, we suggest that long-term color change in males during the breeding season reflects male alternative mating tactics. Upon encounter with a receptive female, males rapidly alter their appearance to that of a specific brief courtship display, which reflects their social status. The females, however, copulated indiscriminately in respect to male color patterns. Thus, we suggest that the differential color patterns displayed by males during the breeding season are largely aimed at inter-male signaling. PMID- 27409773 TI - Drive: Theory and Construct Validation. AB - This article explicates the theory of drive and describes the development and validation of two measures. A representative set of drive facets was derived from an extensive corpus of human attributes (Study 1). Operationalised using an International Personality Item Pool version (the Drive:IPIP), a three-factor model was extracted from the facets in two samples and confirmed on a third sample (Study 2). The multi-item IPIP measure showed congruence with a short form, based on single-item ratings of the facets, and both demonstrated cross informant reliability. Evidence also supported the measures' convergent, discriminant, concurrent, and incremental validity (Study 3). Based on very promising findings, the authors hope to initiate a stream of research in what is argued to be a rather neglected niche of individual differences and non-cognitive assessment. PMID- 27409772 TI - Nest Bacterial Environment Affects Microbiome of Hoopoe Eggshells, but Not That of the Uropygial Secretion. AB - The study of associations between symbiotic bacterial communities of hosts and those of surrounding environments would help to understand how bacterial assemblages are acquired, and how they are transmitted from one to another location (i.e. symbiotic bacteria acquisition by hosts). Hoopoes (Upupa epops) smear their eggshells with uropygial secretion (oily secretion produced in their uropygial gland) that harbors antibiotic producing bacteria. Trying to elucidate a possible role of nest material and cloaca microbiota in determining the bacterial community of the uropygial gland and the eggshells of hoopoes, we characterized bacterial communities of nest material, cloaca, uropygial gland and eggshells by the ARISA fingerprinting. Further, by adding material with scarce bacteria and antimicrobial properties, we manipulated the bacterial community of nest material and thus tested experimentally its effects on the microbiomes of the uropygial secretion and of the eggshells. The experiment did not influence the microbiome of the uropygial secretion of females, but affected the community established on eggshells. This is the first experimental evidence indicating that nest material influences the bacterial community of the eggshells and, therefore, probability of embryo infection. Some of the bacterial strains detected in the secretion were also in the bacterial communities of the nest material and of cloaca, but their occurrence within nests was not associated, which suggests that bacterial environments of nest material and cloaca are not sources of symbiotic bacteria for the gland. These results do not support a role of nest environments of hoopoes as reservoirs of symbiotic bacteria. We discuss possible scenarios explaining bacterial acquisition by hoopoes that should be further explored. PMID- 27409774 TI - Hepatic abscess: a rare complication after liver transplant. AB - BACKGROUND: This study was conducted to evaluate the predisposing factors, microbiology, treatment, and outcomes associated with hepatic abscess, a rare but serious complication which may accur after an orthotopic liver transplant (OLT). METHODS: This was a retrospective study based on a prospectively maintained database of 1100 patients who underwent OLT at the Medical University of Warsaw. An abscess was defined on imaging as solitary or multiple localized parenchymal collections in patients with clinical signs of infection, with or without positive cultures from blood or abscess aspirate. RESULTS: Fifteen patients (1.4%) developed hepatic abscess, including 12 (80%) with multiple abscesses. Predisposing factors included biliary pathology (eight patients), hepaticojejunostomy (six patients), and hepatic artery stenosis or thrombosis (five patients). Ten patients were treated using multiple percutaneous and endoscopic interventional procedures in addition to antimicrobial treatment whereas five were treated solely with antibiotics. Five patients (33.3%) died due to multi-organ failure secondary to abscess treatment, including one unsuccessful case of re-OLT. Thirteen patients (87%) had bacterial growth and five (33.3%) had fungal growth in their blood or abscess aspirates. CONCLUSIONS: Hepatic abscess after liver transplantation may be treated successfully with percutaneous and endoscopic intervention, along with antibiotics according to the results of microbial cultures of blood and/or abscess aspirates. PMID- 27409775 TI - Palliative care must progress. PMID- 27409776 TI - Small change, big difference. PMID- 27409777 TI - Childhood lymphoedema and 'Lymphaletics': overcoming barriers. AB - Primary lymphoedema is a complex condition that causes tissue swelling, usually in one or more of the limbs, but lymphatic drainage of the head, trunk or deeper organs may also be affected. It can manifest in swelling at any time from birth meaning there are a number of children affected by this condition. While it is rare in childhood there are too few professionals experienced in diagnosis and treatment, which results in delays in identification and referral to appropriate services for diagnosis and treatment. The Children's Lymphoedema Special Interest Group (CLSIG) was formed in 2010 by a group of lymphoedema specialists in a bid to raise awareness, improve service provision, and enhance practitioner knowledge. One of the aims of the group was to deliver a 'fun day' (Lymphaletics) for children with lymphoedema and their families to encourage physical activity and social interaction with children who have similar problems, and to provide a source of parent-to-parent support. This article discusses the issues for children and their families, and the aims and format of the event. PMID- 27409778 TI - Using new research to improve treatment and management of lymphoedema. PMID- 27409779 TI - BJN Awards 2016: Oedema and Lipoedema Nurse of the Year Runner up 2016. PMID- 27409780 TI - Nurses' experiences of leech therapy in plastic and reconstructive surgery. AB - The aim of this study was to explore nurses' experience of using leech therapy. Leech therapy is useful in promoting revascularisation of skin grafts. Nurse disquiet in their role as leech therapists has been noted. This study explored the experience of Irish nurses. A qualitative design with an interview schedule was used to learn about emotional and practical clinical experiences. Interviews were carried out with seven nurses working with leeches in reconstructive surgery in 2013. These interviews were coded and explored for themes. Results revealed that many nurses feel aversion to the use of leeches. This may be associated with the use of a parasitic organism as treatment in conflict with the nurse's role in cross infection. It was also found that management of a nurse's own and patient's emotional responses is required. In conclusion, preparation for the role of leech therapy beyond the purely practical is necessary, and should explore affective responses of the practitioner and patients. PMID- 27409781 TI - The day surgery experience from the perspective of service users. AB - Although health policy would suggest that day surgery is the best service for patients undergoing a surgical procedure, it is important to consider the patient and whether this type of service is what they want. This information can be generated through a service evaluation with the results used to inform local decision-making, changes to care delivery and improvements in patient care. This article describes the results of a service evaluation performed in a single-site day surgery unit. PMID- 27409782 TI - Can NHS politics, power and conflict ever be a good thing for nurses? AB - This article explores how organisational politics, power and conflict have a positive role to play for nurses in NHS organisational change and improvement, rather than always leading to disagreement and dispute. PMID- 27409783 TI - 'So why did you become a nurse?' Reflections from a second-year student. PMID- 27409784 TI - Patient safety in acute care: are we going around in circles? AB - This article provides a critical discussion examining why adult patients continue to unnecessarily deteriorate and die despite repeated healthcare policy initiatives. After considering the policy background and reviewing current trends in the data, it proposes some solutions that, if enacted, would, the authors believe, have a direct impact on survival rates. Health professionals working in hospitals are failing to recognise signs of physiological deterioration. As a result, adult patients are dying unnecessarily, estimated to be in the region of 1000 a month. This is despite international healthcare policy requiring practitioners to be appropriately trained to recognise the deteriorating adult patient and to intervene. A literature review centred on health policy for England from 1999 to 2015 was undertaken, with reference to international policy and practice. This article also draws on the authors' combined clinical experience, which is underpinned by relevant research and theory. The implications for nursing could be significant. Change is urgently required otherwise people will continue to die unnecessarily. Health professionals, healthcare organisations and international governments working together can prevent unnecessary deaths from happening within acute hospitals. PMID- 27409785 TI - The role of service-user feedback in undergraduate nursing courses. AB - There is an increasing expectation that service users should contribute in a meaningful way to student nurse education courses. This article describes how service-user feedback on undergraduate student nurses' performance during practice learning opportunities (PLOs) gives an insight into the qualities service users value in student nurses. At Cardiff University, the new Bachelor of Nursing course, launched in September 2012, took into account the Nursing and Midwifery (NMC) standards for preregistration, implementing a mechanism for service users to feed back on students' clinical performance. To facilitate this service, user/carer feedback pages were inserted into the students' bound clinical practice portfolio. A large sample of the clinical portfolios (n=100) from one cohort across adult, child and mental health nursing fields were examined at the end of year 1, year 2 and again at the end of year 3, and service users' comments collated. In considering the words used by service users, the authors propose that they reflected the six fundamental values-or 6Cs-of care, compassion, competence, communication, courage and commitment that underpin the delivery of excellent care. Conclusions drawn from the feedback were that students exhibited the caring and professional qualities that service users value, and indeed showed the dignity and respect for patients and people that the profession demands. PMID- 27409786 TI - A study into psychosocial factors as predictors of work-related fatigue. AB - OBJECTIVE: To explore and determine relationship between psychosocial factors and work-related fatigue among emergency and critical care nurses in Brunei. METHODS: Cross-sectional study conducted on all emergency and critical care nurses across Brunei public hospitals from February to April 2016. RESULTS: 201 nurses participated in the study (82% response rate). A total of 36% of the variance of chronic fatigue was explained by stress, trust in management, decision latitude, self-rated health, and work-family conflict. Burnout, self-rated health, commitment to workplace, and trust in management explained 30% of the variance of acute fatigue. Stress, work-family conflict and reward explained 28% of the variance of intershift recovery after controlling for significant sociodemographic variables. Smoking was identified as an important sociodemographic factor for work-related fatigue. CONCLUSIONS: Psychosocial factors were good predictors of work-related fatigue. A range of psychosocial factors were established, however more research is required to determine all possible causation factors of nurses' work-related fatigue. PMID- 27409787 TI - Nurse migration and the EU: how are UK nurses prepared? PMID- 27409788 TI - Support for nurses: paying it forward. AB - Sarah Kahn, Deputy Editor, BJN, speaks to Joan Pons Laplana who was awarded third place at this year's BJN Awards for Nurse of the Year. Joan had not wanted to become a nurse, but by sheer luck (realised in retrospect) that is what he ended up doing. Today, he uses his motivation to raise funds and share nursing knowledge. PMID- 27409790 TI - Ensuring optimal health care for LGBT patients. AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses a Royal College of Nursing policy that highlights the complexities of providing high-quality and non-discriminatory health care. PMID- 27409789 TI - Safeguarding research participants who lack decision-making capacity. AB - Richard Griffith outlines the requirements that must be met when conducting research with participants who lack decision-making capacity. What legal and ethical issues must researchers bear in mind? PMID- 27409791 TI - A rocky road lies ahead for the Healthcare Safety Investigation Branch. AB - John Tingle discusses the expert advisory group report on the establishment of the new healthcare safety organisation for England that came into existence on 1 April 2016. PMID- 27409792 TI - From staff nurse to nurse consultant. PMID- 27409793 TI - Being positive about reshaping roles. PMID- 27409794 TI - Expression of the Bovine NK-Lysin Gene Family and Activity against Respiratory Pathogens. AB - Unlike the genomes of many mammals that have a single NK-lysin gene, the cattle genome contains a family of four genes, one of which is expressed preferentially in the lung. In this study, we compared the expression of the four bovine NK lysin genes in healthy animals to animals challenged with pathogens known to be associated with bovine respiratory disease (BRD) using transcriptome sequencing (RNA-seq). The expression of several NK-lysins, especially NK2C, was elevated in challenged relative to control animals. The effects of synthetic peptides corresponding to functional region helices 2 and 3 of each gene product were tested on both model membranes and bio-membranes. Circular dichroism spectroscopy indicated that these peptides adopted a more helical secondary structure upon binding to an anionic model membrane and liposome leakage assays suggested that these peptides disrupt membranes. Bacterial killing assays further confirmed the antimicrobial effects of these peptides on BRD-associated bacteria, including both Pasteurella multocida and Mannhemia haemolytica and an ultrastructural examination of NK-lysin-treated P. multocida cells by transmission electron microscopy revealed the lysis of target membranes. These studies demonstrate that the expanded bovine NK-lysin gene family is potentially important in host defense against pathogens involved in bovine respiratory disease. PMID- 27409795 TI - Identification of Novel Variants in LTBP2 and PXDN Using Whole-Exome Sequencing in Developmental and Congenital Glaucoma. AB - BACKGROUND: Primary congenital glaucoma (PCG) is the most common form of glaucoma in children. PCG occurs due to the developmental defects in the trabecular meshwork and anterior chamber of the eye. The purpose of this study is to identify the causative genetic variants in three families with developmental and primary congenital glaucoma (PCG) with a recessive inheritance pattern. METHODS: DNA samples were obtained from consanguineous families of Pakistani ancestry. The CYP1B1 gene was sequenced in the affected probands by conventional Sanger DNA sequencing. Whole exome sequencing (WES) was performed in DNA samples of four individuals belonging to three different CYP1B1-negative families. Variants identified by WES were validated by Sanger sequencing. RESULTS: WES identified potentially causative novel mutations in the latent transforming growth factor beta binding protein 2 (LTBP2) gene in two PCG families. In the first family a novel missense mutation (c.4934G>A; p.Arg1645Glu) co-segregates with the disease phenotype, and in the second family a novel frameshift mutation (c.4031_4032insA; p.Asp1345Glyfs*6) was identified. In a third family with developmental glaucoma a novel mutation (c.3496G>A; p.Gly1166Arg) was identified in the PXDN gene, which segregates with the disease. CONCLUSIONS: We identified three novel mutations in glaucoma families using WES; two in the LTBP2 gene and one in the PXDN gene. The results will not only enhance our current understanding of the genetic basis of glaucoma, but may also contribute to a better understanding of the diverse phenotypic consequences caused by mutations in these genes. PMID- 27409796 TI - Mesenchymal Stromal Cells Epithelial Transition Induced by Renal Tubular Cells Derived Extracellular Vesicles. AB - Mesenchymal-epithelial interactions play an important role in renal tubular morphogenesis and in maintaining the structure of the kidney. The aim of this study was to investigate whether extracellular vesicles (EVs) produced by human renal proximal tubular epithelial cells (RPTECs) may induce mesenchymal epithelial transition of bone marrow-derived mesenchymal stromal cells (MSCs). To test this hypothesis, we characterized the phenotype and the RNA content of EVs and we evaluated the in vitro uptake and activity of EVs on MSCs. MicroRNA (miRNA) analysis suggested the possible implication of the miR-200 family carried by EVs in the epithelial commitment of MSCs. Bone marrow-derived MSCs were incubated with EVs, or RPTEC-derived total conditioned medium, or conditioned medium depleted of EVs. As a positive control, MSCs were co-cultured in a transwell system with RPTECs. Epithelial commitment of MSCs was assessed by real time PCR and by immunofluorescence analysis of cellular expression of specific mesenchymal and epithelial markers. After one week of incubation with EVs and total conditioned medium, we observed mesenchymal-epithelial transition in MSCs. Stimulation with conditioned medium depleted of EVs did not induce any change in mesenchymal and epithelial gene expression. Since EVs were found to contain the miR-200 family, we transfected MSCs using synthetic miR-200 mimics. After one week of transfection, mesenchymal-epithelial transition was induced in MSCs. In conclusion, miR-200 carrying EVs released from RPTECs induce the epithelial commitment of MSCs that may contribute to their regenerative potential. Based on experiments of MSC transfection with miR-200 mimics, we suggested that the miR 200 family may be involved in mesenchymal-epithelial transition of MSCs. PMID- 27409799 TI - Different methods for subgingival application of chlorhexidine in the treatment of patients with chronic periodontitis. AB - OBJECTIVE: The aim of this study was to evaluate clinical efficacy of different chlorhexidine gluconate (CHX) preparations applied subgingivally as an adjunct to scaling and root planing (SRP). MATERIAL AND METHODS: A total of 120 periodontal pockets was included in this randomized, controlled, split mouth designed study. According to protocols used in treatment, periodontal pockets were assigned to experimental and control groups as follows: CHX solution as an addition to SRP versus control SRP group; CHX gel as an addition to SRP versus control SRP; CHX chip as an addition to SRP versus control SRP group. Following clinical parameters were recorded at baseline, one and three months after the baseline: plaque index (PI), probing pocket depth (PPD), bleeding index (BI) and clinical attachment level (CAL). RESULTS: The most significant improvements were found concerning PI in CHX solution with SRP and CHX gel with SRP groups over controls at one month recall, as well as concerning BI and PPD in CHX chip with SRP group over SRP alone at three-month recall. CONCLUSION: Results of this study favour combination therapy using CHX chip as an adjunct to SRP due to greater improvements in BI and PPD compared to those obtained by SRP alone in the treatment of chronic periodontitis. PMID- 27409797 TI - The Role of Grunt Calls in the Social Dominance Hierarchy of the White-Lipped Peccary (Mammalia, Tayassuidae). AB - Grunt-like calls are present in the vocal repertoire of many group-living mammals and seem to facilitate social interactions between lower and higher-ranking members. The white-lipped peccary (Tayassu pecari) lives in stable hierarchical mixed-sex groups and like non-human primates, usually emits grunt-like calls following aggressive interactions, mainly during feeding contexts. We investigated the possible functions of peccaries' grunt-like calls and their relationship to the individuals' social rank, identity, and sexual dimorphism. We observed that low-ranking individuals emitted grunt-like calls more often than high-ranking ones, and that the alpha male never emitted this vocalization. Moreover, the mean minimum frequency of grunt-like calls decreased as the peccary's rank increased. The findings revealed differences among individual grunts, but the low accuracy of cross-validation (16%) suggests that individual recognition in peccaries may be less important than an honest signal of individual social status. In addition, the absence of differences in the acoustic parameters of grunt-like calls between males and females points to the lack of sexual dimorphism in this species. We verified that after hearing grunt calls, dominant opponents were more likely to cease attacking a victim, or at least delay the continuation of conflict, probably decreasing the severity of agonistic interactions. Our findings are particularly important to improve the current understanding of the role of grunt-like calls in herd-living mammals with linear dominant hierarchies, and strongly suggest that they are involved in the maintenance of herd social stability and cohesion. PMID- 27409800 TI - Depression as a mediator in the relationship between perceived familial criticism and college adaptation. AB - OBJECTIVE: This study examined relationships among emerging adults' perceived familial criticism, their depressive symptoms, and their college adaptation. PARTICIPANTS: The current study examined the responses of 412 emerging adults (300 females and 112 males) who were college students at a large southeastern university. The majority of these emerging adults were Caucasian, but the remainder were from a broad range of racial backgrounds. METHODS: Participants completed the Family Emotional Involvement and Criticism Scale as a measure of their familial criticism, the Student Adaptation to College Questionnaire as a measure of their college adaptation, and the Beck Depression Inventory-Second Edition as a measure of their depression. RESULTS: Results were examined using correlational and regression analyses in the context of Baron and Kenny's (J Pers Soc Psychol. 1986;51:1173-1182) method for determining mediation. Results suggested that for female emerging adults, the relationship between perceived familial criticism and college adaptation was mediated significantly by depressive symptoms. In contrast, this pattern of results did not hold for male emerging adults. CONCLUSIONS: Given these findings, emerging adults' depressive symptoms may serve as a useful proximal target for psychotherapeutic interventions meant to improve adaptation to college (particularly for female emerging adults), even in the context of high levels of perceived familial criticism from emerging adults' family of origin. PMID- 27409801 TI - The Criminalization of Physicians and the Delegitimization of Violence in Turkey. AB - In June 2013, protests that erupted in Gezi Park in Istanbul, Turkey were met with state violence, mobilizing hundreds of native physicians to deliver emergency medical care. Drawing on ethnographic fieldwork in makeshift clinics during these protests, interviews with Gezi physicians and analyses of recent laws restricting emergency care provision, in this article I explore the criminalization of clinical practice through legal and coercive means of the government and the delegitimization of state violence through clinical and expert witnessing practices of physicians. As I show, material, legal, and discursive articulations of the idiom of medical neutrality revolve around the tension between medical praxis as neutrality and medical praxis as political participation. I offer a reconsideration of medical humanitarian and human rights regimes in terms of their consequences for inciting, documenting and restricting state violence. PMID- 27409802 TI - Correction: Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005535.]. PMID- 27409803 TI - Dengue Virus Nonstructural Protein 1 Induces Vascular Leakage through Macrophage Migration Inhibitory Factor and Autophagy. AB - Dengue virus (DENV) is the most common mosquito-borne flavivirus; it can either cause mild dengue fever or the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the characteristic features of DHF/DSS is vascular leakage; although DENV nonstructural protein 1 (NS1) has been proved to induce vascular leakage after binding to Toll-like receptor 4, the down-stream mechanism has not yet been fully understood. In the sera of DENV-infected patients, the concentrations of DENV NS1 and inflammatory cytokine macrophage migration inhibitory factor (MIF) are positively correlated with disease severity, but whether DENV NS1 induces vascular leakage through MIF secretion remains unknown. We demonstrated that recombinant NS1 induced vascular leakage and MIF secretion both in human endothelial cell line HMEC-1 and in mice. Furthermore, these phenomena were inhibited in the presence of anti-NS1 antibodies both in vitro and in vivo. DENV NS1 also induced LC3-I to LC3-II conversion and p62 degradation in endothelial cell line, which indicated the formation of autophagy. To clarify whether MIF or autophagy mediated DENV NS1 induced vascular leakage, various inhibitors were applied. The results showed that DENV NS1-induced vascular leakage and VE-cadherin disarray were blocked in the presence of MIF inhibitors, anti-MIF-antibodies or autophagy inhibitors. An Atg5 knockdown clone further confirmed that autophagy formation of endothelial cells was required in NS1-induced vascular leakage. Furthermore, DENV NS1-induced LC3 puncta were also decreased in the presence of MIF inhibitors, indicating that MIF mediated DENV NS1-induced autophagy. Taken together, the results suggest a potential mechanism of DENV-induced vascular leakage and provide possible therapeutic targets against DHF/DSS. PMID- 27409804 TI - Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival. AB - OBJECTIVES: The long-term clinical characteristics, response to therapy, and survival in patients with immunoglobulin D (IgD) multiple myeloma (MM) were investigated. METHODS: A retrospective study was conducted that included 68 patients treated in the last 10 years, 37 of whom received bortezomib only (bortezomib group), 13 of whom received bortezomib and underwent autologous hematopoietic stem cell transplantation (bortezomib + ASCT group), and 18 of whom received conditional chemotherapy (non-bortezomib group). RESULTS: The ratio of males to females was 44:24, and the median age was 56.5 years. The overall response rate of each group was 91.9, 77.8, and 100%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 24 and 15.5 months, respectively, among the 68 patients. The median OS of each group was 23, 21.5, and 27 months, respectively. The median PFS of each group was 18, 12, and 24 months, respectively. The 3- and 5-year OS were 64 and 45%, respectively, and the 3- and 5-year PFS were 39 and 13%, respectively, among the 68 patients. Cox regression showed that the percentage of bone marrow plasmacytosis was significantly associated with OS (p = 0.038). CONCLUSIONS: The survival of IgD patients is shorter than that of other MM patients. Treatment strategies with bortezomib followed by stem cell transplantation may boost the response rate and improve survival. PMID- 27409805 TI - Corrigendum: Enhancer loops appear stable during development and are associated with paused polymerase. PMID- 27409806 TI - Single-layer MoS2 nanopores as nanopower generators. AB - Making use of the osmotic pressure difference between fresh water and seawater is an attractive, renewable and clean way to generate power and is known as 'blue energy'. Another electrokinetic phenomenon, called the streaming potential, occurs when an electrolyte is driven through narrow pores either by a pressure gradient or by an osmotic potential resulting from a salt concentration gradient. For this task, membranes made of two-dimensional materials are expected to be the most efficient, because water transport through a membrane scales inversely with membrane thickness. Here we demonstrate the use of single-layer molybdenum disulfide (MoS2) nanopores as osmotic nanopower generators. We observe a large, osmotically induced current produced from a salt gradient with an estimated power density of up to 10(6) watts per square metre--a current that can be attributed mainly to the atomically thin membrane of MoS2. Low power requirements for nanoelectronic and optoelectric devices can be provided by a neighbouring nanogenerator that harvests energy from the local environment--for example, a piezoelectric zinc oxide nanowire array or single-layer MoS2 (ref. 12). We use our MoS2 nanopore generator to power a MoS2 transistor, thus demonstrating a self powered nanosystem. PMID- 27409808 TI - Mobile genes in the human microbiome are structured from global to individual scales. AB - Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations. PMID- 27409807 TI - Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. AB - Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers. ILC3 development is thought to be programmed, but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial-ILC3-epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals. PMID- 27409809 TI - Prefrontal neuronal assemblies temporally control fear behaviour. AB - Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses. PMID- 27409812 TI - Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G protein-coupled receptor activation. AB - G-protein-coupled receptors (GPCRs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. Ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signalling effectors such as G proteins and beta-arrestins. It is well known that different agonists can share the same binding pocket but evoke unique receptor conformations leading to a wide range of downstream responses ('efficacy'). Furthermore, increasing biophysical evidence, primarily using the beta2 adrenergic receptor (beta2AR) as a model system, supports the existence of multiple active and inactive conformational states. However, how agonists with varying efficacy modulate these receptor states to initiate cellular responses is not well understood. Here we report stabilization of two distinct beta2AR conformations using single domain camelid antibodies (nanobodies)-a previously described positive allosteric nanobody (Nb80) and a newly identified negative allosteric nanobody (Nb60). We show that Nb60 stabilizes a previously unappreciated low-affinity receptor state which corresponds to one of two inactive receptor conformations as delineated by X-ray crystallography and NMR spectroscopy. We find that the agonist isoprenaline has a 15,000-fold higher affinity for beta2AR in the presence of Nb80 compared to the affinity of isoprenaline for beta2AR in the presence of Nb60, highlighting the full allosteric range of a GPCR. Assessing the binding of 17 ligands of varying efficacy to the beta2AR in the absence and presence of Nb60 or Nb80 reveals large ligand-specific effects that can only be explained using an allosteric model which assumes equilibrium amongst at least three receptor states. Agonists generally exert efficacy by stabilizing the active Nb80-stabilized receptor state (R80). In contrast, for a number of partial agonists, both stabilization of R80 and destabilization of the inactive, Nb60-bound state (R60) contribute to their ability to modulate receptor activation. These data demonstrate that ligands can initiate a wide range of cellular responses by differentially stabilizing multiple receptor states. PMID- 27409810 TI - A comprehensive transcriptional map of primate brain development. AB - The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey. PMID- 27409811 TI - Human gut microbes impact host serum metabolome and insulin sensitivity. AB - Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders. PMID- 27409813 TI - Unexpected role of interferon-gamma in regulating neuronal connectivity and social behaviour. AB - Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-gamma (IFN-gamma)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN gamma and increase GABAergic (gamma-aminobutyric-acid) currents in projection neurons, suggesting that IFN-gamma is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-gamma/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-gamma signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN gamma, in disorders characterized by social dysfunction and suggests a co evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-gamma signalling. PMID- 27409814 TI - Ablation-cooled material removal with ultrafast bursts of pulses. AB - The use of femtosecond laser pulses allows precise and thermal-damage-free removal of material (ablation) with wide-ranging scientific, medical and industrial applications. However, its potential is limited by the low speeds at which material can be removed and the complexity of the associated laser technology. The complexity of the laser design arises from the need to overcome the high pulse energy threshold for efficient ablation. However, the use of more powerful lasers to increase the ablation rate results in unwanted effects such as shielding, saturation and collateral damage from heat accumulation at higher laser powers. Here we circumvent this limitation by exploiting ablation cooling, in analogy to a technique routinely used in aerospace engineering. We apply ultrafast successions (bursts) of laser pulses to ablate the target material before the residual heat deposited by previous pulses diffuses away from the processing region. Proof-of-principle experiments on various substrates demonstrate that extremely high repetition rates, which make ablation cooling possible, reduce the laser pulse energies needed for ablation and increase the efficiency of the removal process by an order of magnitude over previously used laser parameters. We also demonstrate the removal of brain tissue at two cubic millimetres per minute and dentine at three cubic millimetres per minute without any thermal damage to the bulk. PMID- 27409815 TI - Human perception: Amazon music. PMID- 27409816 TI - Indifference to dissonance in native Amazonians reveals cultural variation in music perception. AB - by biology remains debated. One widely discussed phenomenon is that some combinations of notes are perceived by Westerners as pleasant, or consonant, whereas others are perceived as unpleasant,or dissonant. The contrast between consonance and dissonance is central to Western music and its origins have fascinated scholars since the ancient Greeks. Aesthetic responses to consonance are commonly assumed by scientists to have biological roots, and thus to be universally present in humans. Ethnomusicologists and composers, in contrast, have argued that consonance is a creation of Western musical culture. The issue has remained unresolved, partly because little is known about the extent of cross cultural variation in consonance preferences. Here we report experiments with the Tsimane'--a native Amazonian society with minimal exposure to Western culture- and comparison populations in Bolivia and the United States that varied in exposure to Western music. Participants rated the pleasantness of sounds. Despite exhibiting Western-like discrimination abilities and Western-like aesthetic responses to familiar sounds and acoustic roughness, the Tsimane' rated consonant and dissonant chords and vocal harmonies as equally pleasant. By contrast, Bolivian city- and town-dwellers exhibited significant preferences for consonance,albeit to a lesser degree than US residents. The results indicate that consonance preferences can be absent in cultures sufficiently isolated from Western music, and are thus unlikely to reflect innate biases or exposure to harmonic natural sounds. The observed variation in preferences is presumably determined by exposure to musical harmony, suggesting that culture has a dominant role in shaping aesthetic responses to music. PMID- 27409817 TI - POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL. AB - OBJECTIVE: To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). METHODS: The design was a single center, retrospective chart review. Patients treated by the authors from 2008 2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). RESULTS: We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had >=1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. CONCLUSION: LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol. PMID- 27409819 TI - UTILITY OF ULTRASOUND VERSUS GENE EXPRESSION CLASSIFIER IN THYROID NODULES WITH ATYPIA OF UNDETERMINED SIGNIFICANCE. AB - OBJECTIVE: Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset. METHODS: We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology. RESULTS: Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy. CONCLUSION: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder. ABBREVIATIONS: AUS = atypia of undetermined significance FNA = fine-needle aspiration GEC = gene expression classifier GEC-B = GEC-benign GEC-S = GEC suspicious for malignancy NPV = negative predictive value PPV = positive predictive value USG = ultrasonography. PMID- 27409821 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: UPDATE ON GROWTH HORMONE STIMULATION TESTING AND PROPOSED REVISED CUT-POINT FOR THE GLUCAGON STIMULATION TEST IN THE DIAGNOSIS OF ADULT GROWTH HORMONE DEFICIENCY. AB - OBJECTIVE: The clinical features of adult GH deficiency (GHD) are nonspecific, and GH stimulation testing is often required to confirm the diagnosis. However, diagnosing adult GHD can be challenging due to the episodic and pulsatile GH secretion, concurrently modified by age, gender, and body mass index (BMI). METHODS: PubMed searches were conducted to identify published data since 2009 on GH stimulation tests used to diagnose adult GHD. Relevant articles in English language were identified and considered for inclusion in the present document. RESULTS: Testing for confirmation of adult GHD should only be considered if there is a high pretest probability, and the intent to treat if the diagnosis is confirmed. The insulin tolerance test (ITT) and glucagon stimulation test (GST) are the two main tests used in the United States. While the ITT has been accepted as the gold-standard test, its safety concerns hamper wider use. Previously, the GH-releasing hormone-arginine test, and more recently the GST, are accepted alternatives to the ITT. However, several recent studies have questioned the diagnostic accuracy of the GST when the GH cut-point of 3 MUg/L is used and have suggested that a lower GH cut-point of 1 MUg/L improved the sensitivity and specificity of this test in overweight/obese patients and in those with glucose intolerance. CONCLUSION: Until a potent, safe, and reliable test becomes available, the GST should remain as the alternative to the ITT in the United States. In order to reduce over-diagnosing adult GHD in overweight/obese patients with the GST, we propose utilizing a lower GH cut-point of 1 MUg/L in these subjects. However, this lower GH cut-point still needs further evaluation for diagnostic accuracy in larger patient populations with varying BMIs and degrees of glucose tolerance. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists BMI = body mass index GH = growth hormone GHD = GH deficiency GHRH = GH-releasing hormone GHS = GH secretagogue GST = glucagon stimulation test IGF = insulin-like growth factor IGFBP-3 = IGF-binding protein 3 ITT = insulin tolerance test ROC = receiver operating characteristic WB-GST = weight-based GST. PMID- 27409823 TI - To The Editor. PMID- 27409822 TI - GUT MICROBIOTA, PREBIOTICS, PROBIOTICS, AND SYNBIOTICS IN MANAGEMENT OF OBESITY AND PREDIABETES: REVIEW OF RANDOMIZED CONTROLLED TRIALS. AB - OBJECTIVE: To review the data from randomized controlled trials (RCTs) for the roles of microbiota, pre-, pro- and synbiotics in metabolic conditions (obesity, prediabetes, and diabetes mellitus type 2 [DM2]). METHODS: Primary literature was reviewed on the topics including RCTs of pre-, pro- and synbiotics use for metabolic disease. RESULTS: Gut bacteria (microbiota) benefit digestion and have multiple other functions. Microbiota could increase harvesting of energy from the food and cause subclinical inflammation seen in metabolic disorders. Diet-related interventions including prebiotics, probiotics, and synbiotics (combining pre-and probiotics) may benefit metabolic conditions. Prebiotics are complex carbohydrates (i.e., dietary fiber). Results of RCTs of prebiotics suggested a neutral effect on body weight, decreased fasting and postprandial glucose, and improved insulin sensitivity and lipid profile. Some inflammation markers were reduced, sometimes substantially (20-30%). RCTs for probiotics demonstrated significant but small effects on body weight (<3%) and metabolic parameters. The effect was seen mostly with fermented milk or yogurt compared to capsule form, consumption for at least 8 weeks, and use of multiple rather than a single bacterial strain. Changes in microbiota were seen at times with both pre- and probiotics. Pickled and fermented foods, particularly vegetables and beans, could serve as a dietary source of pre-, pro-, and synbiotics. These foods showed possible benefits for morbidity and mortality in prospective cohort studies. CONCLUSION: Pre-, pro-, and synbiotics could prove useful, but further research is needed to clarify their clinical relevance for the prevention and management of metabolic disease. ABBREVIATIONS: A1c = glycohemoglobin A1c CI = confidence interval CVD = cardiovascular disease GMB = gut (large bowel) microbiota DM2 = diabetes mellitus type 2 HOMA-IR = homeostatic model assessment of insulin resistance LDL = low-density lipoprotein LPS = lipopolysaccharide NAFLD = nonalcoholic fatty liver disease RCT = randomized controlled trial SMD = standardized mean difference TG = triglycerides. PMID- 27409824 TI - Statistical guidance for responsible data sharing: an overview. PMID- 27409826 TI - Intraocular Pressure Spikes after Aflibercept Intravitreal Injections. AB - The objective of this study was to assess the intraocular pressure (IOP) as well as the anatomical modifications of the anterior segment following an aflibercept injection. Patients underwent an aflibercept intravitreal injection (IVI) (0.05 ml) with a 30.5-gauge needle and an antireflux system. IOP was assessed before injection (T0), immediately after (T1), and 5 min (T5), 15 min (T15), and 45 min (T45) after the IVI. Before the IVI and immediately after the T1 measurement, a PENTACAM(r) acquisition was used to evaluate the anterior chamber parameters (anterior chamber volume, depth and measure of the iridocorneal angle). At T0, IOP was 12.9 +/- 1.3 mm Hg. IOP significantly increased after IVI (42.7 +/- 3 mm Hg, p < 0.001). IOP returned to baseline at T45 (13.0 +/- 1.2 mm Hg, p = 0.877). Anterior chamber volume decreased after IVI (160.6 vs. 168.3 mm3, p = 0.002). No significant changes were found for iridocorneal angle and anterior chamber depth. Aflibercept IVI causes an acute increase in IOP over a short period without iridocorneal angle closure. PMID- 27409825 TI - Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling. AB - The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities. PMID- 27409827 TI - Targeting alphavbeta3 and alphavbeta5 integrins inhibits pulmonary metastasis in an intratibial xenograft osteosarcoma mouse model. AB - Osteosarcoma is an aggressive bone cancer that has a high propensity for metastasis to the lungs. Patients with metastatic disease face a very poor prognosis. Therefore, novel therapeutics, efficiently suppressing the metastatic process, are urgently needed. Integrins play a pivotal role in tumor cell adhesion, motility and metastasis. Here, we evaluated alphavbeta3 and alphavbeta5 integrin inhibition with cilengitide as a novel metastasis-suppressive therapeutic approach in osteosarcoma. Immunohistochemical analysis of alphavbeta3 and alphavbeta5 integrins expression in a tissue microarray of tumor specimens collected from osteosarcoma patients revealed that alphavbeta5 integrin is mainly found on tumor cells, whereas alphavbeta3 is predominantly expressed by stromal cells. In vitro functional assays demonstrated that cilengitide dose-dependently inhibited de novo adhesion, provoked detachment and inhibited migration of osteosarcoma cell lines. Cilengitide induced a decline in cell viability, blocked the cell cycle in the G1 phase and caused anoikis by activation of the Hippo pathway. In a xenograft orthotopic mouse model cilengitide minimally affected intratibial primary tumor growth but, importantly, suppressed pulmonary metastasis. The data demonstrate that targeting alphavbeta3 and alphavbeta5 integrins in osteosarcoma should be considered as a novel therapeutic option for patients with metastatic disease. PMID- 27409828 TI - Oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) as second-line therapy for patients with advanced urothelial cancer. AB - There is currently no standard treatment for metastatic urothelial cancer after failure of cisplatin-based therapy. The present retrospective study investigated the efficacy and safety of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOX) in locally advanced or metastatic urothelial cancer patients following cisplatin-based treatment. Thirty-three patients who had received one or two cisplatin-based regimens were treated with oxaliplatin (85 mg/m2) as a 2-h infusion on day 1, LV (200 mg/m2) as a 2-h infusion followed by bolus 5-FU (400 mg/m2) on day 1, or a 44-h continuous 5-FU (1,200 mg/m2) infusion. Patients were a mean of 67 years old with two involved organs. Metastases were mostly in the lung (43%), lymph nodes (51%) and liver (46%). Based on an intention-to-treat analysis, nine patients achieved a partial response, with an overall response rate of 27%. Eight (24%) patients had stable disease. Mean progression-free survival was 3 months and mean overall survival was 6.1 months. Toxicity was mild to moderate with grade 3 or 4 neutropenia, thrombocytopenia and neuropathy occurring in 5 (15%), 4 (12%) and 2 (6%) patients, respectively. This study demonstrated that oxaliplatin plus 5-FU/LV was a well-tolerated second-line regimen with moderate activity in patients pretreated with cisplatin-based therapeutics. PMID- 27409829 TI - Sex-specific clinicopathological significance of novel (Frizzled-7) and established (MGMT, IDH1) biomarkers in glioblastoma. AB - BACKGROUND: The Wnt receptor Frizzled-7 (FZD7) promotes tumor progression and can be currently targeted by monoclonal antibody therapy. Here, we determined the prognostic value of FZD7 for the overall survival of glioblastoma (GBM) patients, both as individual marker and taken in combination with the previously-described markers MGMT and IDH1. Additionally, we tested whether these markers (alone or in combination) exhibited sex-specific differences. RESULTS: High levels of FZD7 (FZD7high) associated with shorter survival in GBM patients; however, FZD7high was a significant predictor of poor survival only in male patients. Mutation of IDH1 significantly associated with longer survival in male but not female patients. Methylated MGMT promoter significantly associated with longer survival only in female patients. Combination of FZD7 with MGMT enhanced the prognostic accuracy and abrogated the sex differences observed upon single marker analysis. Combination of FZD7 with IDH1 was a significant predictor of survival in male GBM patients only. MATERIALS AND METHODS: Three independent cohorts of patients with primary GBM (n=120, n=108 and n=105, respectively) were included in this study. FZD7 and IDH1 were assessed by immunohistochemistry in tissue microarrays. MGMT promoter methylation was determined by methylation-specific polymerase chain reaction. Survival analysis was performed by Kaplan-Meier estimate, log-rank test and Cox proportional hazard regression. CONCLUSIONS: Our study identifies novel individual and combination markers with prognostic and, possibly, therapeutic relevance in GBM. Furthermore, our findings substantiate the importance of sexual dimorphism in this type of cancer. PMID- 27409830 TI - Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior. AB - Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches. PMID- 27409831 TI - Divergent in vitro/in vivo responses to drug treatments of highly aggressive NIH Ras cancer cells: a PET imaging and metabolomics-mass-spectrometry study. AB - Oncogenic K-ras is capable to control tumor growth and progression by rewiring cancer metabolism. In vitro NIH-Ras cells convert glucose to lactate and use glutamine to sustain anabolic processes, but their in vivo environmental adaptation and multiple metabolic pathways activation ability is poorly understood. Here, we show that NIH-Ras cancer cells and tumors are able to coordinate nutrient utilization to support aggressive cell proliferation and survival. Using PET imaging and metabolomics-mass spectrometry, we identified the activation of multiple metabolic pathways such as: glycolysis, autophagy recycling mechanism, glutamine and serine/glycine metabolism, both under physiological and under stress conditions. Finally, differential responses between in vitro and in vivo systems emphasize the advantageous and uncontrolled nature of the in vivo environment, which has a pivotal role in controlling the responses to therapy. PMID- 27409832 TI - The dual role of asporin in breast cancer progression. AB - Asporin has been reported as a tumor suppressor in breast cancer, while asporin activated invasion has been described in gastric cancer. According to our in silico search, high asporin expresion associates with significantly better relapse free survival (RFS) in patients with low-grade tumors but RFS is significantly worse in patients with grade 3 tumors. In line with other studies, we have confirmed asporin expression by RNA scope in situ hybridization in cancer associated fibroblasts. We have also found asporin expression in the Hs578T breast cancer cell line which we confirmed by quantitative RT-PCR and western blotting. From multiple testing, we found that asporin can be downregulated by bone morphogenetic protein 4 while upregulation may be facilited by serum-free cultivation or by three dimensional growth in stiff Alvetex scaffold. Downregulation by shRNA inhibited invasion of Hs578T as well as of CAFs and T47D cells. Invasion of asporin-negative MDA-MB-231 and BT549 breast cancer cells through collagen type I was enhanced by recombinant asporin. Besides other investigations, large scale analysis of aspartic acid repeat polymorphism will be needed for clarification of the asporin dual role in progression of breast cancer. PMID- 27409833 TI - Hypoxia-mediated alterations and their role in the HER-2/neuregulated CREB status and localization. AB - The cAMP-responsive element-binding protein (CREB) is involved in the tumorigenicity of HER-2/neu-overexpressing murine and human tumor cells, but a link between the HER-2/neu-mediated CREB activation, its posttranslational modification and localization and changes in the cellular metabolism, due to an altered (tumor) microenvironment remains to be established. The present study demonstrated that shRNA-mediated silencing of CREB in HER-2/neu-transformed cells resulted in decreased tumor formation, which was associated with reduced angiogenesis, but increased necrotic and hypoxic areas in the tumor. Hypoxia induced pCREBSer133, but not pCREBSer121 expression in HER-2/neu-transformed cells. This was accompanied by upregulation of the hypoxia-inducible genes GLUT1 and VEGF, increased cell migration and matrix metalloproteinase-mediated invasion. Treatment of HER-2/neu+ cells with signal transduction inhibitors targeting in particular HER-2/neu was able to revert hypoxia-controlled CREB activation. In addition to changes in the phosphorylation, hypoxic response of HER-2/neu+ cells caused a transient ubiquitination and SUMOylation as well as a co-localization of nuclear CREB to the mitochondrial matrix. A mitochondrial localization of CREB was also demonstrated in hypoxic areas of HER-2/neu+ mammary carcinoma lesions. This was accompanied by an altered gene expression pattern, activity and metabolism of mitochondria leading to an increased respiratory rate, oxidative phosphorylation and mitochondrial membrane potential and consequently to an enhanced apoptosis and reduced cell viability. These data suggest that the HER-2/neu-mediated CREB activation caused by a hypoxic tumor microenvironment contributes to the neoplastic phenotype of HER-2/neu+ cells at various levels. PMID- 27409834 TI - Lgr5+ stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors. AB - Actively proliferating Lgr5+ skin stem cells are found deep in the hair follicle (HF). These cells renew the HF and drive its expansion in anagen phase. Their long residence and continuous mitotic activity make them prime candidates to transform into skin tumor-initiating cells. This was investigated by subjecting Lgr5-EGFP-Ires-CreERT2/R26R-LacZ mice (haired and hairless) to chemical and UV carcinogenic regimens. In the course of these regimens Lgr5+ cells (EGFP+) remained exclusively located in HFs, and in deep-seated cysts of hairless skin. In haired mice, progeny of Lgr5+ stem cells (LacZ+ after a pulse of tamoxifen) appeared in the interfollicular epidermis upon UV-induced sunburn and in TPA induced hyperplasia. In hairless mice the progeny remained located in deep-seated cysts and in HF remnants. Progeny in hairless skin was only detected interfollicularly at a late stage, in between outgrowing tumors. Lgr5+ stem cells were absent in the ultimate tumor masses, and no tumor appeared to be a (clonal) expansion of Lgr5+ cells (52 tumors with tamoxifen at the start of carcinogenesis, 42 tumors with tamoxifen late during tumor outgrowth). In contrast to CD34/K15+ quiescent bulge stem cells, actively proliferating Lgr5+ stem cells do therefore not appear to be tumor drivers in experimental skin carcinogenesis. PMID- 27409835 TI - Deletion of 14-3-3sigma sensitizes mice to DMBA/TPA-induced papillomatosis. AB - The p53-inducible cell cycle regulator 14-3-3sigma exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3sigma/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3sigma expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3sigma causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice. Therefore, loss of 14-3-3sigma function might contribute to epithelial tumor development. Here, we generated mice with loxP sites surrounding the single 14-3-3sigma exon which allowed Cre-mediated deletion of the gene. 14-3-3sigma-deficient mice are viable, but demonstrate a permanently disheveled fur. However, histological analyses of the skin did not reveal obvious defects in the hair follicles or the epidermis. Deletion of 14-3 3sigma did not enhance spontaneous epidermal tumor development, whereas it increased the frequency and size of DMBA/TPA-induced papillomas. In conclusion, 14-3-3sigma is dispensable for normal epidermal homeostasis but critical for suppression of chemically-induced skin carcinogenesis. In addition, these results suggest that the ER mutation of 14-3-3sigma is not equivalent to loss of 14-3 3sigma, but may represent a gain-of-function variant, which does not reflect the organismal function of wild-type 14-3-3sigma. PMID- 27409837 TI - The eIF2alpha serine 51 phosphorylation-ATF4 arm promotes HIPPO signaling and cell death under oxidative stress. AB - The HIPPO pathway is an evolutionary conserved regulator of organ size that controls both cell proliferation and death. This pathway has an important role in mediating cell death in response to oxidative stress through the inactivation of Yes-associated protein (YAP) and inhibition of anti-oxidant gene expression. Cells exposed to oxidative stress induce the phosphorylation of the alpha (alpha) subunit of the translation initiation factor eIF2 at serine 51 (eIF2alphaP), a modification that leads to the general inhibition of mRNA translation initiation. Under these conditions, increased eIF2alphaP facilitates the mRNA translation of activating transcription factor 4 (ATF4), which mediates either cell survival and adaptation or cell death under conditions of severe stress. Herein, we demonstrate a functional connection between the HIPPO and eIF2alphaP-ATF4 pathways under oxidative stress. We demonstrate that ATF4 promotes the stabilization of the large tumor suppressor 1 (LATS1), which inactivates YAP by phosphorylation. ATF4 inhibits the expression of NEDD4.2 and WWP1 mRNAs under pro oxidant conditions, which encode ubiquitin ligases mediating the proteasomal degradation of LATS1. Increased LATS1 stability is required for the induction of cell death under oxidative stress. Our data reveal a previously unidentified ATF4 dependent pathway in the induction of cell death under oxidative stress via the activation of LATS1 and HIPPO pathway. PMID- 27409838 TI - Loss of FBXW7 and accumulation of MCL1 and PLK1 promote paclitaxel resistance in breast cancer. AB - FBXW7 is a component of SCF (complex of SKP1, CUL1 and F-box-protein)-type ubiquitin ligases that targets several oncoproteins for ubiquitination and degradation by the proteasome. FBXW7 regulates cellular apoptosis by targeting MCL1 for ubiquitination. Recently, we identified PLK1 as a new substrate of FBXW7 modulating the intra-S-phase DNA-damage checkpoint. Taxanes are frequently used in breast cancer treatments, but the acquisition of resistance makes these treatments ineffective. We investigated the role of FBXW7 and their substrates MCL1 and PLK1 in regulating the apoptotic response to paclitaxel treatment in breast cancer cells and their expression in breast cancer tissues. Paclitaxel sensitive MDA-MB-468 and a paclitaxel-resistant MDA-MB-468R subclone were used to study the role of FBXW7 and substrates in paclitaxel-induced apoptosis. Forced expression of FBXW7 or downregulation of MCL1 or PLK1 restored sensitivity to paclitaxel in MDA-MB-468R cells. By contrary, FBXW7-silenced MDA-MB-468 cells became resistant to paclitaxel. The expression of FBXW7 and substrates were studied in 296 invasive carcinomas by immunohistochemistry and disease-free survival was analyzed in a subset of patients treated with paclitaxel. In breast cancer tissues, loss of FBXW7 correlated with adverse prognosis markers and loss of FBXW7 and MCL1 or PLK1 accumulation were associated with diminished disease free survival in paclitaxel-treated patients. We conclude that FBXW7 regulates the response to paclitaxel by targeting MCL1 and PLK1 in breast cancer cells and thus targeting these substrates may be a valuable adjunct for paclitaxel treatment. Also, FBXW7, MCL1 and PLK1 may be relevant predictive markers of tumor progression and response to paclitaxel treatment. PMID- 27409839 TI - FGFR3-TACC3 fusion in solid tumors: mini review. AB - Fibroblast growth factor receptors (FGFR) are transmembrane kinase proteins with growing importance in cancer biology given the frequency of molecular alterations and vast interface with multiple other signaling pathways. Furthermore, numerous FGFR inhibitors in clinical development demonstrate the expanding therapeutic relevance of this pathway. Indeed, results from early phase clinical trials already indicate that a subset of patients with advanced tumors derive benefit from FGFR targeted therapies. FGFR gene aberrations and FGFR gene rearrangements are relatively rare in solid malignancies. The recently described FGFR3-TACC3 fusion protein has a constitutively active tyrosine kinase domain and promotes aneuploidy. We summarize the prevalence data on FGFR3-TACC3 fusions among different histological tumor types and the preliminary evidence that this rearrangement represents a targetable molecular aberration in some patients with solid tumors. PMID- 27409844 TI - Optimized moth-eye anti-reflective structures for As2S3 chalcogenide optical fibers. AB - We computationally investigate moth-eye anti-reflective nanostructures imprinted on the endfaces of As2S3 chalcogenide optical fibers. With a goal of maximizing the transmission through the endfaces, we investigate the effect of changing the parameters of the structure, including the height, width, period, shape, and angle-of-incidence. Using these results, we design two different moth-eye structures that can theoretically achieve almost 99.9% average transmisison through an As2S3 surface. PMID- 27409845 TI - Novel scanning method for distortion-free BOTDA measurements. AB - Systematic errors induced by distortions in the pump pulse of conventional Brillouin distributed fiber sensors are thoroughly investigated. Experimental results, supported by a theoretical analysis, demonstrate that the two probe sidebands in standard Brillouin optical time-domain analyzers provide a non-zero net gain on the pump pulse, inducing severe distortions of the pump when scanning the pump-probe frequency offset, especially at high probe power levels. Compared to the impact of non-local effects reported in the state-of-the-art, measurements here indicate that for probe powers in the mW range (below the onset of amplified spontaneous Brillouin scattering), the obtained gain and loss spectra show two strong side-lobes that lead to significant strain/temperature errors. This phenomenon is not related to the well-known spectral hole burning resulting from pump depletion, but it is strictly related to the temporal and spectral distortions that the pump pulse experiences when scanning the Brillouin gain/loss spectrum. As a solution to this problem, a novel scanning scheme for Brillouin sensing is proposed. The method relies on a fixed frequency separation between the two probe sidebands, so that a flat zero net gain is achieved on the pump pulse when scanning the pump-probe frequency offset. The proposed technique is experimentally validated, demonstrating its ability to completely cancel out non local effects up to a probe power ultimately limited by the onset of amplified spontaneous Brillouin scattering. The method allows for one order of magnitude improvement in the figure-of-merit of optimized long-range Brillouin distributed fiber sensors, enabling measurements along a 100 km-long sensing fiber with 2 m spatial resolution and with no need of added features for performance enhancement. PMID- 27409846 TI - Synthesis of MoS2/g-C3N4 nanocomposites with enhanced visible-light photocatalytic activity for the removal of nitric oxide (NO). AB - Molybdenum disulfide and graphitic carbon nitride (MoS2-g C3N4) nanocomposites with visible-light induced photocatalytic activity were successfully synthesized by a facile ultrasonic dispersion method. The crystalline structure and morphology of the MoS2-g-C3N4 nanocomposites were characterized by X-ray diffraction (XRD), transmission electron microcopy (TEM), high-resolution TEM (HRTEM) and scanning electron microscopy (SEM). The optical property of the as-prepared nanocomposites was studied by ultraviolet visible diffusion reflection (UV-vis) and photoluminescence(PL) spectrum. It could be observed from the TEM image that the MoS2 nanosheets and g C3N4 nanoparticles were well combined together. Moreover, the photocatalytic activity of MoS2-g-C3N4 composites was evaluated by the removal of nitric oxide under visible light irradiation (>400nm). The experimental results demonstrated that the nanocomposites with the MoS2 content of 1.5 wt% exhibited optimal photocatalytic activity and the corresponding removal rate of NO achieved 51.67%, higher than that of pure g-C3N4 nanoparticles. A possible photocatalytic mechanism for the MoS2-g-C3N4 nanocomposites with enhanced photocatalytic activity could be ascribed to the hetero-structure of MoS2 and g-C3N4. PMID- 27409847 TI - Ultra-dense spatial-division-multiplexed optical fiber transmission over 6-mode 19-core fibers. AB - Ultra-dense spatial-division multiplexing (SDM) is achieved by mode multiplexed technique with multiple cores in a single fiber, namely few-mode multi-core fiber. Using a 9.8-km six-mode nineteen-core fiber, we demonstrate an ultra-dense SDM transmission of 16-channels wavelength-division-multiplexed (WDM) dual polarization quadrature phase shift keying signals, achieving a record spatial multiplicity of 114. With the help of ultra-dense Super-Nyquist WDM techniques in the 4.5-THz bandwidth of the full C-band, we demonstrate 2.05 Pbit/s transmission over 9.8-km six-mode nineteen-core fibers. In this experiment, the highest aggregate spectral efficiency of 456 bit/s/Hz is achieved. PMID- 27409849 TI - Measurement and suppression of secondary waves caused by high-order modes in a photonic bandgap fiber-optic gyroscope. AB - Air-core photonic bandgap fiber (PBF) is a good choice for fiber-optic gyroscopes (FOGs) owing to the fact that it can be adapted to a wide variety of environments. However, its multimode properties are disadvantageous for the application to FOGs. An interference-based method is proposed to precisely determine the secondary waves caused by the high-order modes and their coupling. Based on the method, two groups of secondary waves have been found, having optical path differences (OPDs) of ~1.859 m and ~0.85 m, respectively, relative to the primary waves in a PBFOG that consists of a 7-cell PBF coil, approximately 180 m in length. Multi-turn bends of the PBF at both ends of the PBF coil after the fusion splicing points are shown to suppress the intensity of these secondary waves by approximately 10 dB. PMID- 27409848 TI - Novel ray tracing method for stray light suppression from ocean remote sensing measurements. AB - We developed a new integrated ray tracing (IRT) technique to analyze the stray light effect in remotely sensed images. Images acquired with the Geostationary Ocean Color Imager show a radiance level discrepancy at the slot boundary, which is suspected to be a stray light effect. To determine its cause, we developed and adjusted a novel in-orbit stray light analysis method, which consists of three simulated phases (source, target, and instrument). Each phase simulation was performed in a way that used ray information generated from the Sun and reaching the instrument detector plane efficiently. This simulation scheme enabled the construction of the real environment from the remote sensing data, with a focus on realistic phenomena. In the results, even in a cloud-free environment, a background stray light pattern was identified at the bottom of each slot. Variations in the stray light effect and its pattern according to bright target movement were simulated, with a maximum stray light ratio of 8.5841% in band 2 images. To verify the proposed method and simulation results, we compared the results with the real acquired remotely sensed image. In addition, after correcting for abnormal phenomena in specific cases, we confirmed that the stray light ratio decreased from 2.38% to 1.02% in a band 6 case, and from 1.09% to 0.35% in a band 8 case. IRT-based stray light analysis enabled clear determination of the stray light path and candidates in in-orbit circumstances, and the correction process aided recovery of the radiometric discrepancy. PMID- 27409850 TI - Stimulated polariton scattering in an intracavity RbTiOPO4 crystal generating frequency-tunable THz output. AB - A high power, frequency-tunable THz source based on intracavity stimulated polariton scattering (SPS) in RbTiOPO4 (RTP) is demonstrated for the first time. Frequency tunable THz output was obtained from 3.10 to 4.15 THz, with a gap at 3.17 to 3.49 THz, arising from the 104 cm-1 A1 mode in RTP. A maximum average output power of 16.2 uW was detected at 3.8 THz. This is the highest average output power ever reported for an intracavity polariton laser. PMID- 27409851 TI - Making metals transparent: a circuit model approach. AB - Solid metal films are well known to be opaque to electromagnetic waves over a wide frequency range, from low frequency to optics. High values of the conductivity at relatively low frequencies or negative values of the permittivity at the optical regime provide the macroscopic explanation for such opacity. In the microwave range, even extremely thin metal layers (much smaller than the skin depth at the operation frequency) reflect most of the impinging electromagnetic energy, thus precluding significant transmission. However, a drastic resonant narrow-band enhancement of the transparency has recently been reported. The quasi transparent window is opened by placing the metal film between two symmetrically arranged and closely spaced copper strip gratings. This letter proposes an analytical circuit model that yields a simple explanation to this unexpected phenomenon. The proposed approach avoids the use of lengthy numerical calculations and suggests how the transmissivity can be controlled and enhanced by manipulating the values of the electrical parameters of the associated circuit model. PMID- 27409852 TI - Hybrid layered polymer slot waveguide Young interferometer. AB - We demonstrate a polymer slot waveguide Young interferometer coated with a bilayer of Al2O3/TiO2. The approach enables relaxed dimensions of the polymer waveguide which simplifies the fabrication of the structure with a resolution of 50 nm. The layers were coated by an atomic layer deposition technique. The feasibility of the device was investigated by exploiting the interferometric structure as a bulk refractive index sensor operating at 975 nm wavelength for detection of an ethanol-water solution. A refractive index change of 1 * 10-6 RIU with a sensing length of only 800 um was detected. The approach confirms the possibility of realizing a low cost device with a small footprint and enhanced sensitivity by employing the TiO2 rails in the sides of the slot waveguide. PMID- 27409853 TI - Self-compressed, spectral broadening of a Yb:YAG thin-disk amplifier. AB - We demonstrate pulse shortening of 1-ps Yb:YAG thin-disk regenerative amplifier to 500 fs by cross-polarized wave generation (XPW) in a 6 mm BaF2 crystal. The process is self-compressed and has 8.5% conversion efficiency corresponding to 18 uJ energy. Our theoretical and experimental investigation shows that the factor of 3 spectral broadening and pulse shortening in ps-XPW generation only happens in unsaturated regime. We demonstrate that the initial spectral chirp affects the spectral broadening and pulse shortening of XPW pulses. PMID- 27409854 TI - Large-mode-area fibers operating near single-mode regime. AB - Lower NA in large-mode-area fibers enables better single-mode operation and larger core diameters. Fiber NA has traditionally been limited to 0.06, mostly due to the control tolerance in the fabrication process. It has been recognized recently that transverse mode instability is a major limit to average power scaling in fiber lasers. One effective method to mitigate this limit is to operate nearer to the single-mode regime. Lower fiber NA is critical in this since it allows relatively larger core diameters which is the key to mitigate the limits imposed by nonlinear effects. We have developed a fabrication process of ytterbium-doped silica glass which is capable of highly accurate refractive index control and sufficient uniformity for LMA fibers. This process is also capable of large-volume production. It is based on a significant amount of post-processing once the fiber preforms are made. We have demonstrated 30/400 and 40/400 LMA fibers with a NA of ~0.028 operating very close to the single-mode regime. The second-order mode cuts off at ~1.2MUm and ~1.55um respectively. We have also studied issues related to bend losses due to the low NA and further optimization of LMA fibers. PMID- 27409855 TI - Trapping and controlling the dispersive wave within a solitonic well. AB - We have numerically studied the effect of mutual interactions between soliton and dispersive waves and the possibility to create a solitonic well consisting of initial twin-solitons moving away from each other to trap the incident dispersive wave. Different from the case of the solitonic cage formed by the velocity matched twin-solitons, the intense dispersive wave can break up into small pulses, which are almost completely trapped within the solitonic well. Moreover, the corresponding spectrum of the trapped dispersive wave can be narrowed firstly and then expanded, and a new dispersive wave can be generated as the twin solitons collision occurred. By adjusting either the peak power or temporal width of incident dispersive wave, both the intensity of the collision-induced dispersive wave and the position where it is generated can be controlled. PMID- 27409856 TI - Empirical formulas for calculating loss in hollow core tube lattice fibers. AB - In this paper scaling laws governing loss in hollow core tube lattice fibers are numerically investigated and discussed. Moreover, by starting from the analysis of the obtained numerical results, empirical formulas for the estimation of the minimum values of confinement loss, absorption loss, and surface scattering loss inside the transmission band are obtained. The proposed formulas show a good accuracy for fibers designed for applications ranging from THz to ultra violet band. PMID- 27409857 TI - Visual inspection of 3-D surface and refractive-index profiles of microscopic lenses using a single-arm off-axis holographic interferometer. AB - A single-arm off-axis holographic interferometer (SA-OHI) system for visual inspection of the three-dimensional (3-D) surfaces and refractive-index profiles of micrometer-scale optical lenses is proposed. In this system, a couple of pellicle beam splitters and optical mirrors are employed to generate two sheared off-axis beams from the single object beam by controlling the tilted angle of the optical mirror. Each sheared beam is divided into two areas with and without object data, which are called half-object and half-reference beams, respectively. These sub-divided object and reference beams then make interference patterns, just like the conventional two-arm holographic interferometer. This holographic interferometer system, called SA-OHI, can solve the DC bias, virtual and duplicated image problems occurred in most lateral shearing interferometers, which allow extraction of the hologram data only related to the target object. The operational principle of the proposed system is analyzed based on ray-optics. To confirm the feasibility of the proposed system in the practical application fields, experiments with test lenses are also carried out and the results are comparatively discussed with those of the conventional system. PMID- 27409858 TI - High average power third harmonic generation at 355 nm with K3B6O10Br crystal. AB - We demonstrate a nanosecond 355 nm laser by third harmonic generation of an Nd: YAG laser with a 4 * 4 * 13.3 mm3 type I cut K3B6O10Br crystal for the first time. The maximum average power of 19.3 W is achieved with the corresponding conversion efficiency of 16.3% and the maximum conversion efficiency of 18.3% is recorded when the 355 nm average power is 15.8W. In addition, several nonlinear optical parameters including the angle and temperature bandwidths at third harmonic generation are also investigated. PMID- 27409859 TI - Hybrid micro/nano-structure formation by angular laser texturing of Si surface for surface enhanced Raman scattering. AB - Surface enhanced Raman spectroscopy (SERS) has drawn much research interest in the past decades as an efficient technique to detect low-concentration molecules. Among many technologies, which can be used to fabricate SERS substrates, laser ablation is a simple and high-speed method to produce large-area SERS substrates. This work investigates the angular texturing effect by dynamic laser ablation and its influence on SERS signals. By tuning the angle between the Si surface and laser irradiation, the distributions and sizes of laser induced hybrid micro/nano structures are studied. By decorating with a silver film, plenty of hot spots can be created among these structures for SERS. It is found that when the incident laser angle is 15 degrees at the laser fluence of 16.0 J/cm2, the SERS performance is well optimized. This work realizes antisymmetric distribution of nanoparticles deposited on Si surface, which provides a flexible tuning of the hybrid micro/nano-structures' fabrication with high controllability for practical applications. PMID- 27409860 TI - Optical full-depth refocusing of 3-D objects based on subdivided-elemental images and local periodic delta-functions in integral imaging. AB - We propose a new approach for optical refocusing of three-dimensional (3-D) objects on their real depth without a pickup-range limitation based on subdivided elemental image arrays (sub-EIAs) and local periodic delta-function arrays (L PDFAs). The captured EIA from the 3-D objects locating out of the pickup-range, is divided into a number of sub-EIAs depending on the object distance from the lens array. Then, by convolving these sub-EIAs with each L-PDFA whose spatial period corresponds to the specific object's depth, as well as whose size is matched to that of the sub-EIA, arrays of spatially-filtered sub-EIAs (SF-sub EIAs) for each object depth can be uniquely extracted. From these arrays of SF sub-EIAs, 3-D objects can be optically reconstructed to be refocused on their real depth. Operational principle of the proposed method is analyzed based on ray optics. In addition, to confirm the feasibility of the proposed method in the practical application, experiments with test objects are carried out and the results are comparatively discussed with those of the conventional method. PMID- 27409861 TI - Cylindrical vector beam generation in fiber with mode selectivity and wavelength tunability over broadband by acoustic flexural wave. AB - Theoretical analysis and experimental demonstration are presented for the generation of cylindrical vector beams (CVBs) via mode conversion in fiber from HE11 mode to TM01 and TE01 modes, which have radial and azimuthal polarizations, respectively. Intermodal coupling is caused by an acoustic flexural wave applied on the fiber, whereas polarization control is necessary for the mode conversion, i.e. HE11x->TM01 and HE11y >TE01 for acoustic vibration along the x-axis. The frequency of the RF driving signal for actuating the acoustic wave is determined by the phase matching condition that the period of acoustic wave equals the beatlength of two coupled modes. With phase matching condition tunability, this approach can be used to generate different types of CVBs at the same wavelength over a broadband. Experimental demonstration was done in the visible and communication bands. PMID- 27409862 TI - Passively Q-switched waveguide lasers based on two-dimensional transition metal diselenide. AB - We reported on the passively Q-switched waveguide lasers based on few-layer transition metal diselenide, including molybdenum diselenide (MoSe2) and tungsten diselenide (WSe2), as saturable absorbers. The MoSe2 and WSe2 membranes were covered on silica wafers by chemical vapor deposition (CVD). A low-loss depressed cladding waveguide was produced by femtosecond laser writing in a Nd:YAG crystal. Under optical pump at 808 nm, the passive Q-switching of the Nd:YAG waveguide lasing at 1064 nm was achieved, reaching maximum average output power of 115 mW (MoSe2) and 45 mW (WSe2), respectively, which are corresponding to single-pulse energy of 36 nJ and 19 nJ. The repetition rate of the Q-switched waveguide lasers was tunable from 0.995 to 3.334 MHz (MoSe2) and 0.781 to 2.938 MHz (WSe2), and the obtained minimum pulse duration was 80ns (MoSe2) and 52 ns (WSe2), respectively. PMID- 27409863 TI - CW EC-QCL-based sensor for simultaneous detection of H2O, HDO, N2O and CH4 using multi-pass absorption spectroscopy. AB - A sensor system based on a continuous wave, external-cavity quantum-cascade laser (CW EC-QCL) was demonstrated for simultaneous detection of atmospheric H2O, HDO, N2O and CH4 using a compact, dense pattern multi-pass gas cell with an effective path-length of 57.6 m. The EC-QCL with a mode-hop-free spectral range of 1225-1285 cm-1 operating at ~7.8 um was scanned covering four neighboring absorption lines, for H2O at 1281.161 cm-1, HDO at 1281.455 cm-1, N2O at 1281.53 cm-1 and CH4 at 1281.61 cm 1. A first-harmonic-normalized wavelength modulation spectroscopy with second-harmonic detection (WMS-2f/1f) strategy was employed for data processing. An Allan-Werle deviation analysis indicated that minimum detection limits of 1.77 ppmv for H2O, 3.92 ppbv for HDO, 1.43 ppbv for N2O, and 2.2 ppbv for CH4 were achieved with integration times of 50-s, 50-s, 100-s and 129-s, respectively. Experimental measurements of ambient air are also reported. PMID- 27409864 TI - Control of photo-induced voltages in plasmonic crystals via spin-orbit interactions. AB - There is wide interest in understanding and leveraging the nonlinear plasmon induced potentials of nanostructured materials. We investigate the electrical response produced by spin-polarized light across a large-area bottom-up assembled 2D plasmonic crystal. Numerical approximations of the Lorentz forces provide quantitative agreement with our experimentally-measured DC voltages. We show that the underlying mechanism of the spin-polarized voltages is a gradient force that arises from asymmetric, time-averaged hotspots, whose locations shift with the chirality of light. Finally, we formalize the role of spin-orbit interactions in the shifted intensity patterns and significantly advance our understanding of the physical phenomena, often related to the spin Hall effect of light. PMID- 27409865 TI - One-shot and aberration-tolerable homodyne detection for holographic storage readout through double-frequency grating-based lateral shearing interferometry. AB - A simple method to decode the stored phase signal of volume holographic data storage with adequate wave aberration tolerance is highly demanded. We proposed and demonstrated a one-shot scheme to decode a binary-phase encoding signal through double-frequency-grating based shearing interferometry (DFGSI). The lateral shearing amount is dependent on the focal length of the collimated lens and the frequency difference between the gratings. Diffracted waves with phase encoding were successfully decoded through experimentation. An optical model for the DFGSI was built to analyze phase-error induction and phase-difference control by shifting the double-frequency grating longitudinally and laterally, respectively. The optical model was demonstrated experimentally. Finally, a high aberration tolerance of the DFGSI was demonstrated using the optical model. PMID- 27409866 TI - Coherent cavity-enhanced dual-comb spectroscopy. AB - Dual-comb spectroscopy allows for the rapid, multiplexed acquisition of high resolution spectra without the need for moving parts or low-resolution dispersive optics. This method of broadband spectroscopy is most often accomplished via tight phase locking of two mode-locked lasers or via sophisticated signal processing algorithms, and therefore, long integration times of phase coherent signals are difficult to achieve. Here we demonstrate an alternative approach to dual-comb spectroscopy using two phase modulator combs originating from a single continuous-wave laser capable of > 2 hours of coherent real-time averaging. The dual combs were generated by driving the phase modulators with step-recovery diodes where each comb consisted of > 250 teeth with 203 MHz spacing and spanned > 50 GHz region in the near-infrared. The step-recovery diodes are passive devices that provide low-phase-noise harmonics for efficient coupling into an enhancement cavity at picowatt optical powers. With this approach, we demonstrate the sensitivity to simultaneously monitor ambient levels of CO2, CO, HDO, and H2O in a single spectral region at a maximum acquisition rate of 150 kHz. Robust, compact, low-cost and widely tunable dual-comb systems could enable a network of distributed multiplexed optical sensors. PMID- 27409867 TI - 3D integrated hybrid silicon laser. AB - Lasers were realized on silicon by flip-chip bonding of indium phosphide (InP) devices containing total internal reflection turning mirrors for surface emission. Light is coupled to the silicon waveguides through surface grating couplers. With this technique, InP lasers were integrated on silicon. Laser cavities were also formed by coupling InP reflective semiconductor optical amplifiers to microring resonator filters and distributed Bragg reflector mirrors. Single-mode continuous wave lasing was demonstrated with a side mode suppression ratio of 30 dB. Up to 2 mW of optical power was coupled to the silicon waveguide. Thermal simulations were also performed to evaluate the low thermal impedance afforded by this architecture and potential for high wall-plug efficiency. PMID- 27409868 TI - Generalized revival and splitting of an arbitrary optical field in GRIN media. AB - Assuming a non-paraxial propagation operator, we study the propagation of an electromagnetic field with an arbitrary initial condition in a quadratic GRIN medium. We show analytically that at certain specific periodic distances, the propagated field is given by the fractional Fourier transform of a superposition of the initial field and of a reflected version of it. We also prove that for particular wavelengths, there is a revival and a splitting of the initial field. We apply this results, first to an initial field given by a Bessel function and show that it splits into two generalized Bessel functions, and second, to an Airy function. In both cases our results are compared with the numerical ones. PMID- 27409869 TI - Ultrafast pulse compression, stretching-and-recompression using cholesteric liquid crystals. AB - We have experimentally demonstrated the feasibility of direct compression, or stretching and recompression of laser pulses in a very wide temporal time scale spanning 10's fs to ~1 ps time with sub-mm thick cholesteric liquid crystal (CLC) cells. The mechanisms at work here are the strong dispersion at the photonic band edges and nonlinear phase modulation associated with the non-resonant ultrafast molecular electronic optical nonlinearity. The observed pulse compression limit, spectral characteristics and intensity dependence of the compression are in good agreement with theoretical expectations and simulations based on a coupled-mode propagation model. Owing to the large degree of freedom to engineer the wavelength locations of CLC photonic bandgap and band-edges, these self-action all-optical processes can be realized with ultrafast lasers pulses in a very wide spectral region from the visible to near infrared, with potential applications in compact ultrafast photonic modulation devices/platforms. PMID- 27409870 TI - Experimental demonstration of reduced tilt-to-length coupling by a two-lens imaging system. AB - The coupling between beam tilt and longitudinal path length readout in a setup representing a LISA test mass interferometer was reduced to below 2 um/rad using a two lens imaging system. This was achieved by the use of a homodyne equal arm length Mach-Zehnder interferometer and suppression of the dominating effects of higher order Gaussian modes and longitudinal actuator movement. The latter was subtracted using the phase signal of a large single element photo diode. PMID- 27409871 TI - Improving the signal-to-noise ratio of single-pixel imaging using digital microscanning. AB - Single-pixel cameras provide a means to perform imaging at wavelengths where pixelated detector arrays are expensive or limited. The image is reconstructed from measurements of the correlation between the scene and a series of masks. Although there has been much research in the field in recent years, the fact that the signal-to-noise ratio (SNR) scales poorly with increasing resolution has been one of the main limitations prohibiting the uptake of such systems. Microscanning is a technique that provides a final higher resolution image by combining multiple images of a lower resolution. Each of these low resolution images is subject to a sub-pixel sized lateral displacement. In this work we apply a digital microscanning approach to an infrared single-pixel camera. Our approach requires no additional hardware, but is achieved simply by using a modified set of masks. Compared to the conventional Hadamard based single-pixel imaging scheme, our proposed framework improves the SNR of reconstructed images by ~ 50 % for the same acquisition time. In addition, this strategy also provides access to a stream of low-resolution 'preview' images throughout each high-resolution acquisition. PMID- 27409872 TI - Algebraic cancellation of polarisation noise in fibre interferometers. AB - This experiment uses digital interferometry to reduce polarisation noise from a fiber interferometer to the level of double Rayleigh backscatter making precision fiber metrology systems robust for remote field applications. This is achieved with a measurement of the Jones matrix with interferometric sensitivity in real time, limited only by fibre length and processing bandwidth. This new approach leads to potentially new metrology applications and the ability to do ellipsometry without polarisation elements in the output field. PMID- 27409873 TI - Efficient rational Chebyshev pseudo-spectral method with domain decomposition for optical waveguides modal analysis. AB - We propose an accurate and computationally efficient rational Chebyshev multi domain pseudo-spectral method (RC-MDPSM) for modal analysis of optical waveguides. For the first time, we introduce rational Chebyshev basis functions to efficiently handle semi-infinite computational subdomains. In addition, the efficiency of these basis functions is enhanced by employing an optimized algebraic map; thus, eliminating the use of PML-like absorbing boundary conditions. For leaky modes, we derived a leaky modes boundary condition at the guide-substrate interface providing an efficient technique to accurately model leaky modes with very small refractive index imaginary part. The efficiency and numerical precision of our technique are demonstrated through the analysis of high-index contrast dielectric and plasmonic waveguides, and the highly-leaky ARROW structure; where finding ARROW leaky modes using our technique clearly reflects its robustness. PMID- 27409874 TI - Optimized SESAMs for kilowatt-level ultrafast lasers. AB - We present a thorough investigation of surface deformation and thermal properties of high-damage threshold large-area semiconductor saturable absorber mirrors (SESAMs) designed for kilowatt average power laser oscillators. We compare temperature rise, thermal lensing, and surface deformation of standard SESAM samples and substrate-removed SESAMs contacted using different techniques. We demonstrate that for all cases the thermal effects scale linearly with the absorbed power, but the contacting technique critically affects the strength of the temperature rise and the thermal lens of the SESAMs (i.e. the slope of the linear change). Our best SESAMs are fabricated using a novel substrate-transfer direct bonding technique and show excellent surface flatness (with non measureable radii of curvature (ROC), compared to astigmatic ROCs of up to 10 m for standard SESAMs), order-of-magnitude improved heat removal, and negligible deformation with absorbed power. This is achieved without altering the saturation behavior or the recovery parameters of the samples. These SESAMs will be a key enabling component for the next generation of kilowatt-level ultrafast oscillators. PMID- 27409875 TI - Laser-induced Hertzian fractures in silica initiated by metal micro-particles on the exit surface. AB - Laser-induced Hertzian fractures on the exit surface of silica glass are found to result from metal surface-bound micro particles. Two types of metal micro-spheres are studied (stainless-steel and Al) using ultraviolet laser light. The fracture initiation probability curve as a function of fluence is obtained, resulting in an initiation threshold fluence of 11.1 +/- 4.7 J/cm2 and 16.5 +/- 4.5 J/cm2 for the SS and Al particles, accordingly. The modified damage density curve is calculated based on the fracture probability. The calculated momentum coupling coefficient linking incident laser fluence to the resulting plasma pressure is found to be similar for both particles: 32.6 +/- 15.4 KN/J and 28.1 +/- 10.4 KN/J for the SS and Al cases accordingly. PMID- 27409876 TI - Low-power motion gesture sensor with a partially open cavity package. AB - In an IR proximity-based motion gesture sensor (MGS) mainly composed of an IR LED and photodiodes (PDs), the IR LED is the most power-hungry component. For reducing its power, both the size and the field-of-view (FOV) of each PD can be increased instead. However, it cannot be adapted to conventional MGSs due to the geometrical limitation of their optical structures. In this paper, the optical structure of the proposed MGS with a partially open cavity package allows for power reduction by at least 70.9% compared with conventional MGSs. Optical simulation and test results validate the theoretical analysis presented. PMID- 27409877 TI - Two-tier calibrated electro-optic sensing system for intense field characterization of high-power W-band gyrotron. AB - We present a field-calibrated electro-optic sensing system for measurement of the electric field radiating from a high-power vacuum oscillator at ~95 GHz. The intense electric field is measured in absolute scale via two probe-calibration steps, associated with a photonic heterodyne scheme. First, a micro-electro-optic probe, fabricated to less than one-tenth the oscillation wavelength scale to minimize field-perturbation due to the probe, is placed on the aperture of a field-calculable WR-10 waveguide to calibrate the probe in V/m scale. Then, using this arrangement as a calibrated reference probe at the first-tier position, another probe-bulkier, and thus more robust and sensitive but not accessible to the aperture-is calibrated at the second-tier position away from the waveguide aperture. This two-tier calibrated probe was utilized to diagnose the sub-MV/m scale of intense electric fields and emissions from a high-power W-band gyrotron. The experimental results obtained proved consistent with calculated analytical results-verifying the efficacy of the developed system. PMID- 27409878 TI - Engineered emissivity of textile fabrics by the inclusion of ceramic particles. AB - Composite textile materials, created from a blend of different fibers, have long been used to engineer the properties and performance of fabrics to combine comfort with functionality, such as to create materials with differing optical properties. Some changes to the optical properties of materials in the infrared are subtle and difficult to measure. We present a measurement technique, experimental apparatus, and associated data analysis procedure for detecting small changes in the emissivity of fabrics in the mid-infrared wavelength range (7.5-14 um). Using this technique, we demonstrate that the emissivity of polyester fabric can be engineered controllably via the inclusion of ceramic microparticles within the fabric fibers. PMID- 27409879 TI - Aberration correction for direct laser written waveguides in a transverse geometry. AB - The depth dependent spherical aberration is investigated for ultrafast laser written waveguides fabricated in a transverse writing geometry using the slit beam shaping technique in the low pulse repetition rate regime. The axial elongation of the focus caused by the aberration leads to a distortion of the refractive index change, and waveguides designed as single mode become multimode. We theoretically estimate a depth range over which the aberration effects can be compensated simply by adjusting the incident laser power. If deeper fabrication is required, it is demonstrated experimentally that the aberration can be successfully removed using adaptive optics to fabricate single mode optical waveguides over a depth range > 1 mm. PMID- 27409880 TI - Femtosecond harmonic mode-locking of a fiber laser at 3.27 GHz using a bulk-like, MoSe2-based saturable absorber. AB - We experimentally demonstrate the use of a bulk-like, MoSe2-based saturable absorber (SA) as a passive harmonic mode-locker for the production of femtosecond pulses from a fiber laser at a repetition rate of 3.27 GHz. By incorporating a bulk-like, MoSe2/PVA-composite-deposited side-polished fiber as an SA within an erbium-doped-fiber-ring cavity, mode-locked pulses with a temporal width of 737 fs to 798 fs can be readily obtained at various harmonic frequencies. The fundamental resonance frequency and the maximum harmonic resonance frequency are 15.38 MHz and 3.27 GHz (212th harmonic), respectively. The temporal and spectral characteristics of the output pulses are systematically investigated as a function of the pump power. The output pulses exhibited Gaussian-temporal shapes irrespective of the harmonic order, and even when their spectra possessed hyperbolic-secant shapes. The saturable absorption and harmonic mode-locking performance of our prepared SA are compared with those of previously demonstrated SAs that are based on other transition metal dichalcogenides (TMDs). To the best of the authors' knowledge, the repetition rate of 3.27 GHz is the highest frequency that has ever been demonstrated regarding the production of femtosecond pulses from a fiber laser that is based on SA-induced passive harmonic mode-locking. PMID- 27409881 TI - Design and simulation of two-section DFB lasers with short active-section lengths. AB - Distributed feedback lasers comprised of a reflection section and an active section have been proposed for high direct-modulation bandwidth. The reflection section has the same core layer as the active section so butt-joint re-growth is avoided. Without current injection the reflection section will be pumped to near transparency by the emission from the laser itself so high reflection (> 0.75) can still be achieved as confirmed by the simulation. Therefore a short (150 um) active section can be used, which enables a low threshold current (~5 mA) and a high direct modulation bandwidth (>30 GHz) as demonstrated by the simulation. PMID- 27409882 TI - Special cascade LMS equalization scheme suitable for 60-GHz RoF transmission system. AB - We design a specific cascade least mean square (LMS) equalizer and to the best of our knowledge, it is the first time this kind of equalizer has been employed for 60-GHz millimeter-wave (mm-wave) radio over fiber (RoF) system. The proposed cascade LMS equalizer consists of two sub-equalizers which are designated for optical and wireless channel compensations, respectively. We control the linear and nonlinear factors originated from optical link and wireless link separately. The cascade equalization scheme can keep the nonlinear distortions of the RoF system in a low degree. We theoretically and experimentally investigate the parameters of the two sub-equalizers to reach their best performances. The experiment results show that the cascade equalization scheme has a faster convergence speed. It needs a training sequence with a length of 10000 to reach its stable status, which is only half as long as the traditional LMS equalizer needs. With the utility of a proposed equalizer, the 60-GHz RoF system can successfully transmit 5-Gbps BPSK signal over 10-km fiber and 1.2-m wireless link under forward error correction (FEC) limit 10-3. An improvement of 4dBm and 1dBm in power sensitivity at BER 10-3 over traditional LMS equalizer can be observed when the signals are transmitted through Back-to-Back (BTB) and 10-km fiber 1.2-m wireless links, respectively. PMID- 27409883 TI - Tunable double resonance of silver nanodecahedron on the insulator/conductor film. AB - The generation of double resonance in a nanostructure, thus permitting the modulation of optical field at two frequencies simultaneously, offers new application opportunities for surface enhanced Raman scattering (SERS) and surface enhanced fluorescence (SEF). Here, we present a simple composite nanostructure of silver nanodecahedron (Ag ND)/silica spacer/gold film/glass substrate for achieving double resonance under the normal incidence of polarized light. The optical responses of the composite structure have been theoretically studied by varying the thickness of silica spacer layer from 5 nm to 35 nm for mediating the interaction between Ag ND and gold film. Results indicate that the extinction spectrum of the composite system is strongly dependent on the separation between Ag ND and gold film. The electric field and charge distribution during resonance have been investigated in order to obtain a detailed understanding on the coupling between these two objects. More importantly, due to the anisotropic geometry of Ag ND, double resonance with two plasmonic modes (dipole and gap modes) whose responses can be adjusted through varying the size of Ag ND and mediating its coupling with the gold film respectively, has been achieved in the composite structure under the excitation with polarization parallel to the Ag ND edge adjacent to the spacer surface. The knowledge gained through this work will benefit the development of applications based on local field enhancement. PMID- 27409884 TI - Generalised Cornu spirals: an experimental study using hard x-rays. AB - The Cornu spiral is a graphical aid that has been used historically to evaluate Fresnel integrals. It is also the Argand-plane mapping of a monochromatic complex scalar plane wave diffracted by a hard edge. We have successfully reconstructed a Cornu spiral due to diffraction of hard x-rays from a piece of Kapton tape. Additionally, we have explored the generalisation of the Cornu spiral by observing the Argand-plane mapping of complex scalar electromagnetic fields diffracted by a cylinder and a sphere embedded within a cylinder. PMID- 27409885 TI - Spatial modeling of optical crosstalk in InGaAsP Geiger-mode APD focal plane arrays. AB - We report a spatial model of optical crosstalk in InGaAsP Geiger-mode APD focal plane arrays created via non-sequential ray tracing. Using twenty-four equivalent experimental data sets as a baseline, we show that experimental results can be reproduced to a high degree of accuracy by incorporating secondary crosstalk effects, with reasonable assumptions of material and emission source properties. We use this model to categorize crosstalk according to source and path, showing that the majority of crosstalk in the immediate neighborhood of avalanching pixels in the present devices can be attributed to direct line-of-sight emissions. PMID- 27409886 TI - Modulation transfer spectroscopy in a lithium atomic vapor cell. AB - We have investigated modulation transfer spectroscopy of D2 transitions of 7Li atoms in a vapor cell. The role of the intensity of the probe beam in the spectrum is important, we have seen unique characteristics of the signal in the crossover peak. In order to find the best signal for laser locking, the slope and frequency offset of the zero-crossing signal are determined. The dependence of the modulation transfer spectra on polarizations of pump and probe beam is demonstrated. The residual amplitude modulation in the system is also considered, and the distortion of the spectra due to the modulation is analyzed. It was found that the crossover peak is more suitable for frequency stabilization due to its better residual amplitude modulation compensation. PMID- 27409887 TI - Highly efficient tunable and localized on-chip electrical plasmon source using protruded metal-insulator-metal structure. AB - A compact and highly efficient tunable and localized source of propagating surface plasmon-polaritons is proposed based on a protruded metal-insulator-metal (pMIM) structure. The protrusion along a segment of the pMIM forms a nanometer gap and allows a low voltage bias to generate a localized tunneling current. The tunneling current excited plasmons can be fully coupled to the metal-insulator metal (MIM) waveguiding segment of the pMIM without leakage and propagate a long distance as the gap in the MIM waveguiding segment is much larger than the gap in the protruded segment of the pMIM. Eigenmode and numerical analyses show that by using MIM structures as a benchmark, the pMIM structure enhances the total amount of average power that is transferred from the tunneling current into the excitation of intrinsic eigenmodes of the MIM waveguiding segment. Depending on the magnitude of the applied voltage bias, the pMIM structure supports single, dual and multi modes for a typical Au-SiO2-Au design with a 500 nm thick SiO2. Among all excited modes, the single mode operation allows highly efficient excitation of long travelling surface plasmon-polaritons (SPPs) of up to 30 um. The electrical excitation of SPPs using pMIM structures opens up the possibility of integrating plasmon sources into nanoscale optoelectronic circuits to facilitate on-chip data communications. PMID- 27409888 TI - Passively Q-switched Er3+-doped fiber lasers using colloidal PbS quantum dot saturable absorber. AB - We report on the demonstration of a passively Q-switched 1.55 um fiber laser utilizing a colloidal PbS quantum dot (QD) thin film as a saturable absorber. Colloidal PbS QD films have several features that are advantageous in passively Q switched fiber laser operation, including a large operation wavelength range, cost-effectiveness, and a low saturable absorption intensity. We conducted thorough material and optical studies to verify the advantages of PbS QDs in Q switched laser operation and successfully generated 801 nJ pulses with a 24.2 kHz repetition rate. To the best of our knowledge, the developed Q-switched fiber laser is the first based on colloidal PbS QDs. PMID- 27409889 TI - Propagation properties of Laguerre-Gaussian correlated Schell-model beam in non Kolmogorov turbulence. AB - Analytical formulas are derived for the average intensity, the root-mean-square (rms) angular width, and the M2-factor of Laguerre-Gaussian correlated Schell-model (LGCSM) beam propagating in non-Kolmogorov turbulence. The influence of the beam and turbulence parameters on the LGCSM beam is numerically calculated. It is shown that the quality of the LGCSM beam can be improved by choosing appropriate beam or turbulence parameter values. It is also found that the LGCSM beam has advantage over the Gaussian Schell-model (GSM) beam for reducing the turbulence-induced degradation. Our results will have some theoretical reference value for optical communications. PMID- 27409890 TI - High power and single mode quantum cascade lasers. AB - We present a single mode quantum cascade laser with nearly 1 W optical power. A buried distributed feedback reflector is used on the back section for wavelength selection. The laser is 6 mm long, 3.5 MUm wide, mounted episide-up and the laser facets are left uncoated. Laser emission is centered at 4.68 MUm. Single-mode operation with a side mode suppression ratio of more than 30 dB is obtained in whole range of operation. Farfield measurements prove a symmetric, single transverse-mode emission in TM00-mode with typical divergences of 41 degrees and 33 degrees in the vertical and horizontal direction respectively. This work shows the potential for simple fabrication of high power lasers compatible with standard DFB processing. PMID- 27409891 TI - Ultrafast photoprotective properties of the sunscreening agent octocrylene. AB - Today octocrylene is one of the most common molecules included in commercially available sunscreens. It provides broadband photoprotection for the skin from incident UV-A and UV-B radiation of the solar spectrum. In order to understand how octocrylene fulfils its role as a sunscreening agent, femtosecond pump-probe transient electronic UV-visible absorption spectroscopy is utilised to investigate the ultrafastnonradiative relaxation mechanism of octocrylene in cyclohexane or methanol after UV-B photoexcitation. The data presented clearly shows that UV-B photoexcited octocrylene exhibits ultrafast-nonradiative relaxation mechanisms to repopulate its initial ground state within a few picoseconds, which, at the very least, photophysically justifies its wide spread inclusion in commercial sunscreens. PMID- 27409892 TI - Wavefront metrology for coherent hard X-rays by scanning a microsphere. AB - Characterization of the wavefront of an X-ray beam is of primary importance for all applications where coherence plays a major role. Imaging techniques based on numerically retrieving the phase from interference patterns are often relying on an a-priori assumption of the wavefront shape. In Coherent X-ray Diffraction Imaging (CXDI) a planar incoming wave field is often assumed for the inversion of the measured diffraction pattern, which allows retrieving the real space image via simple Fourier transformation. It is therefore important to know how reliable the plane wave approximation is to describe the real wavefront. Here, we demonstrate that the quantitative wavefront shape and flux distribution of an X ray beam used for CXDI can be measured by using a micrometer size metal-coated polymer sphere serving in a similar way as the hole array in a Hartmann wavefront sensor. The method relies on monitoring the shape and center of the scattered intensity distribution in the far field using a 2D area detector while raster scanning the microsphere with respect to the incoming beam. The reconstructed X ray wavefront was found to have a well-defined central region of approximately 16 um diameter and a weaker, asymmetric, intensity distribution extending 30 um from the beam center. The phase front distortion was primarily spherical with an effective radius of 0.55 m which matches the distance to the last upstream beam defining slit, and could be accurately represented by Zernike polynomials. PMID- 27409893 TI - Atomic coherence effects in four-wave mixing process of a ladder-type atomic system. AB - We investigate the effects of atomic coherence on four-wave mixing (FWM), with respect to the transition routes between the hyperfine states in the 5S1/2-5P3/2-5D5/2 transition of 87Rb atoms. By comparing the FWM spectra with the electromagnetically induced transparency (EIT) spectra of the hyperfine states, we confirm that the FWM process is significantly influenced by both ladder-type and V-type two-photon coherences. From the observed FWM signal of each hyperfine structure, we clarify the role of two-photon coherence in the FWM process under EIT, double-resonance optical pumping (DROP), and two-photon absorption (TPA) conditions in a ladder type atomic system, which is dependent on the open degree of the hyperfine states, the laser intensity, and the laser frequency detuning. PMID- 27409894 TI - Heralded single-photon source utilizing highly nondegenerate, spectrally factorable spontaneous parametric downconversion. AB - We report on the generation of an indistinguishable heralded single-photon state, using highly nondegenerate spontaneous parametric downconversion (SPDC). Spectrally factorable photon pairs can be generated by incorporating a broadband pump pulse and a group-velocity matching (GVM) condition in a periodically-poled potassium titanyl phosphate (PPKTP) crystal. The heralding photon is in the near IR, close to the peak detection efficiency of off-the-shelf Si single-photon detectors; meanwhile, the heralded photon is in the telecom L-band where fiber losses are at a minimum. We observe spectral factorability of the SPDC source and consequently high purity (90%) of the produced heralded single photons by several different techniques. Because this source can also realize a high heralding efficiency (> 90%), it would be suitable for time-multiplexing techniques, enabling a pseudo-deterministic single-photon source, a critical resource for optical quantum information and communication technology. PMID- 27409895 TI - New hybrid genetic particle swarm optimization algorithm to design multi-zone binary filter. AB - The binary phase filters have been used to achieve an optical needle with small lateral size. Designing a binary phase filter is still a scientific challenge in such fields. In this paper, a hybrid genetic particle swarm optimization (HGPSO) algorithm is proposed to design the binary phase filter. The HGPSO algorithm includes self-adaptive parameters, recombination and mutation operations that originated from the genetic algorithm. Based on the benchmark test, the HGPSO algorithm has achieved global optimization and fast convergence. In an easy-to perform optimizing procedure, the iteration number of HGPSO is decreased to about a quarter of the original particle swarm optimization process. A multi-zone binary phase filter is designed by using the HGPSO. The long depth of focus and high resolution are achieved simultaneously, where the depth of focus and focal spot transverse size are 6.05lambda and 0.41lambda, respectively. Therefore, the proposed HGPSO can be applied to the optimization of filter with multiple parameters. PMID- 27409896 TI - Fabrication of a concave grating with a large line spacing via a novel dual-beam interference lithography method. AB - We introduce a novel dual-beam interference lithography (IL) method that makes it possible to fabricate a concave grating with a large line spacing. A concave lens is placed between two point sources for spatial interference and a concave substrate to produce the grating pattern. The original positions of the two point sources are separated by the concave lens, which permits the IL method to fabricate a concave grating that bypasses the line spacing limitation of the conventional IL system. A concave grating with a line spacing of about 3.8 MUm was fabricated and fitted inside a miniature spectrometer. The enlarged line spacing reduces the detector length by 66.5%, while keeping the resolution better than 1.5 nm over a wide spectral band (360 - 825 nm). PMID- 27409897 TI - Improving spatial resolution of confocal Raman microscopy by super-resolution image restoration. AB - A new super-resolution image restoration confocal Raman microscopy method (SRIR RAMAN) is proposed for improving the spatial resolution of confocal Raman microscopy. This method can recover the lost high spatial frequency of the confocal Raman microscopy by using Poisson-MAP super-resolution imaging restoration, thereby improving the spatial resolution of confocal Raman microscopy and realizing its super-resolution imaging. Simulation analyses and experimental results indicate that the spatial resolution of SRIR-RAMAN can be improved by 65% to achieve 200 nm with the same confocal Raman microscopy system. This method can provide a new tool for high spatial resolution micro-probe structure detection in physical chemistry, materials science, biomedical science and other areas. PMID- 27409898 TI - 4 channel * 10 Gb/s bidirectional optical subassembly using silicon optical bench with precise passive optical alignment. AB - We demonstrate an advanced structure for optical interconnect consisting of 4 channel * 10 Gb/s bidirectional optical subassembly (BOSA) formed using silicon optical bench (SiOB) with tapered fiber guiding holes (TFGHs) for precise and passive optical alignment of vertical-cavity surface-emitting laser (VCSEL)-to multi mode fiber (MMF) and MMF-to-photodiode (PD). The co-planar waveguide (CPW) transmission line (Tline) was formed on the backside of silicon substrate to reduce the insertion loss of electrical data signal. The 4 channel VCSEL and PD array are attached at the end of CPW Tline using a flip-chip bonder and solder pad. The 12-channel ribbon fiber is simply inserted into the TFGHs of SiOB and is passively aligned to the VCSEL and PD in which no additional coupling optics are required. The fabricated BOSA shows high coupling efficiency and good performance with the clearly open eye patterns and a very low bit error rate of less than 10-12 order at a data rate of 10 Gb/s with a PRBS pattern of 231-1. PMID- 27409899 TI - Gain-guided soliton fiber laser with high-quality rectangle spectrum for ultrafast time-stretch microscopy. AB - The ultrafast time-stretch microscopy has been proposed to enhance the temporal resolution of a microscopy system. The optical source is a key component for ultrafast time-stretch microscopy system. Herein, we reported on the gain-guided soliton fiber laser with high-quality rectangle spectrum for ultrafast time stretch microscopy. By virtue of the excellent characteristics of the gain-guided soliton, the output power and the 3-dB bandwidth of the stable mode-locked soliton could be up to 3 mW and 33.7 nm with a high-quality rectangle shape, respectively. With the proposed robust optical source, the ultrafast time-stretch microscopy with the 49.6 MUm resolution and a scan rate of 11 MHz was achieved without the external optical amplification. The obtained results demonstrated that the gain-guided soliton fiber laser could be used as an alternative high quality optical source for ultrafast time-stretch microscopy and will introduce some applications in fields such as biology, chemical, and optical sensing. PMID- 27409900 TI - Single shot embedded surface plasmon microscopy with vortex illumination. AB - In previous work we demonstrated how a confocal microscope with a spatial light modulator in the back focal plane could perform accurate measurement of the k vector of a propagating surface plasmon. This involved forming an embedded interferometer between light incident close to normal incidence (reference beam) and light incident at the angle to excite surface plasmons (sample beam). The signal from the interferometer was extracted by stepping the phase of the reference beam relative to the sample beam using a spatial light modulator; this requires at least 3 phase steps, which limits the speed of operation. To overcome this and extract the same information with a single measurement, we project an azimuthal varying phase between 0 and 2pi in the central region of the back focal plane; corresponding to small angles of incidence. This projects a vortex beam as the reference, so that the phase of the reference beam varies with azimuthal angle. By extracting the interference signal from different portions of the reference beam, different phase steps between the reference and the sample are obtained, so all the values required for phase reconstruction can be extracted simultaneously. It is thus possible to obtain the same information with a single shot measurement, at each defocus position, without additional changes to the back focal plane illumination. Results are presented to show that the vortex illuminated sample provides similar results to the phase stepped version, whose values are, in turn, validated with ellipsometry and surface profilometry. PMID- 27409901 TI - Efficient, designable, and broad-bandwidth optical extinction via aspect-ratio tailored silver nanodisks. AB - Subwavelength resonators, ranging from single atoms to metallic nanoparticles, typically exhibit a narrow-bandwidth response to optical excitations. We computationally design and experimentally synthesize tailored distributions of silver nanodisks to extinguish light over broad and varied frequency windows. We show that metallic nanodisks are 2-10x more efficient in absorbing and scattering light than common structures, and can approach fundamental limits to broadband scattering for subwavelength particles. We measure broadband extinction per volume that closely approaches theoretical predictions over three representative visible-range wavelength windows, confirming the high efficiency of nanodisks and demonstrating the collective power of computational design and experimental precision for developing new photonics technologies. PMID- 27409902 TI - Quantum coherence and quantum correlation of two qubits mediated by a one dimensional plasmonic waveguide. AB - We investigate the dynamics of quantum coherence and quantum correlation of two qubits mediated by a one-dimensional plasmonic waveguide. The analytical expression of the dissipative dynamics of the two qubits is obtained for the initial X state. The dynamical behaviors of the quantum coherence and quantum correlation are shown to be largely dependent on the parameters of the initial state. Starting from a product state, quantum coherence and quantum correlation can be induced by the plasmonic waveguide. Under continuous drivings, steady quantum correlation can be obtained at specific distance larger than the operating wavelength and large values of steady quantum coherence are attainable at arbitrary distance. The detuning effect on the dissipation-driven generation of steady quantum coherence and quantum correlation is also explored. PMID- 27409903 TI - Investigation on sensitivity enhancement for optical fiber speckle sensors. AB - We present a detailed theoretical and experimental study on the sensitivity enhancement for multimode fiber (MMF) speckle sensor. Using mode coupling theory, we derive an expression showing that the sensitivity of the MMF speckle sensor depends on the intensity profile of the MMF modes. Particularly, we use our theory to study the influence of the spatial filtering window on the sensitivity, and the experimental results have found a good agreement with the theory. Our results suggest that the sensitivity of an MMF speckle sensor can be greatly enhanced by adjusting the size and location of the spatial filtering window. An 80-fold improvement on sensitivity was achieved in our experiment, as compared with the conventional MMF speckle sensor with the filtering window placed at the center of the speckle field. PMID- 27409904 TI - Sub-90 fs dissipative-soliton Erbium-doped fiber lasers operating at 1.6 MUm band. AB - We present an L-band dissipative soliton (DS) fiber laser, which can deliver 87.5 fs pulses at 1.6 MUm band. Numerical simulations are used to confirm the DS generation, and prove the pivotal component of the invisible filter with proper bandwidth in the formation of DS pulses. Such a robust, compact ultrafast laser source with higher pulse energy is hence an excellent seed source for L-band amplifiers. The mechanism revealed in the simulations is helpful to develop a unified theory for understanding various mode-locking regimes in normal dispersion lasers. PMID- 27409905 TI - Spiral spectrum of Airy beams propagation through moderate-to-strong turbulence of maritime atmosphere. AB - The spatial coherence radius in moderate-to-strong maritime turbulence is derived on the basis of the modified Rytov approximation. Models are developed to simulate the spiral spectrum of Airy beams propagating through moderate-to-strong maritime turbulence. In the moderate-to-strong irradiance fluctuation region, we analyze the effects of maritime turbulence on the spread of the spiral spectrum of Airy beams in a horizontal propagation path. Results indicate that the increment in the inner-scale significantly increases the received power. By contrast, the outer-scale elicits a negligible effect on the received power if the ratio of the inner-scale to the outer-scale is less than 0.01. The outer scale affects the received power only if the ratio is greater than 0.01. The performance of a light source is essential for the received power of Airy beams carrying orbital angular momentum (OAM) through moderate-to-strong maritime turbulence. Airy beams with longer wavelengths, smaller OAM numbers, larger radii of the main ring, and smaller diameters of the circular aperture are less affected by maritime turbulence. Autofocusing of Airy beams is beneficial for the propagation of the spiral spectrum in a certain propagation distance. These results contribute to the design of optical communication systems with OAM encoding for moderate-to-strong maritime turbulence. PMID- 27409906 TI - Flavin mononucleotide biomolecular laser: longitudinal mode structure, polarization, and temporal characteristics as probes of local chemical environment. AB - A detailed characterization of the flavin mononucleotide (FMN) biomolecular laser, optically pumped in a stable resonator, is reported here. Photoexcitation of the molecule at 355 nm results in lasing over the ~566.5-573.5 nm spectral region, and the threshold pump energy density is measured to be 110 +/- 10 uJ/mm2 for a 10 mM FMN/water solution. Over twenty longitudinal modes are observed when the cavity length L and the energy pump fluence Ep are 375 um and 300 uJ/mm2, respectively. Partial substitution of glycerol for water as the solvent results in a factor of four reduction in the threshold pump energy fluence (to < 30 uJ/mm2) and a quadrupling of the slope efficiency. This effect is attributed to the O2 - mediated photoconversion of FMN molecules in the triplet state to the singlet species. For pump intensities a factor of 2.5 above threshold, the laser pulse width is ~2 ns FWHM, and the output intensity decays exponentially with a photon lifetime of 1.7 ns. The addition of glycerol to a FMN/water solution also suppresses s-polarized emission (yielding P = 0.78 +/- 0.08), presumably as a result of the inhibition of FMN rotational diffusion. The sensitivity of the spectral and optical properties of this and other biomolecular lasers to the chemical environment underscores the value of coherent emission as a biochemical or biomedical diagnostic tool, particularly insofar as molecule-molecule interactions are concerned. PMID- 27409907 TI - Efficient and pure femtosecond-pulse-length source of polarization-entangled photons. AB - We present a source of polarization entangled photon pairs based on spontaneous parametric downconversion engineered for frequency uncorrelated telecom photon generation. Our source provides photon pairs that display, simultaneously, the key properties for high-performance quantum information and fundamental quantum science tasks. Specifically, the source provides for high heralding efficiency, high quantum state purity and high entangled state fidelity at the same time. Among different tests we apply to our source we observe almost perfect non classical interference between photons from independent sources with a visibility of (100 +/- 5)%. PMID- 27409908 TI - Simulation of aperture-optimised refractive lenses for hard X-ray full field microscopy. AB - The aperture of refractive X-ray lenses is limited by absorption and geometry. We introduce a specific simulation method to develop an aperture-optimized lens design for hard X-ray full field microscopy. The aperture-optimized lens, referred to as Taille-lens, allows for high spatial resolution as well as homogeneous image quality. This is achieved by the individual adaptation of the apertures of hundreds of lens elements of an X-ray imaging lens to the respective microscopy setup. For full field microscopy, the simulations result in lenses with both a large entrance and exit aperture and lens elements with smaller apertures in the middle of the lens. PMID- 27409909 TI - Intracavity characterization of micro-comb generation in the single-soliton regime. AB - Soliton formation in on-chip micro-comb generation balances cavity dispersion and nonlinearity and allows coherent, low-noise comb operation. We study the intracavity waveform of an on-chip microcavity soliton in a silicon nitride microresonator configured with a drop port. Whereas combs measured at the through port are accompanied by a very strong pump line which accounts for >99% of the output power, our experiments reveal that inside the microcavity, most of the power is in the soliton. Time-domain measurements performed at the drop port provide information that directly reflects the intracavity field. Data confirm a train of bright, close to bandwidth-limited pulses, accompanied by a weak continuous wave (CW) background with a small phase shift relative to the comb. PMID- 27409910 TI - Using single side-band modulation for colorless OFDM-WDM access network to alleviate Rayleigh backscattering effects. AB - In this investigation, we demonstrate a new colorless orthogonal-frequency division-multiplexing (OFDM) wavelength-division-multiplexing passive optical network (WDM-PON) system with Rayleigh backscattering (RB) noise mitigation. Here, only a single laser source at the central office (CO) is needed to produce the downstream signal and distributed continuous-wave (CW) carrier, which will then be modulated at the optical networking unit (ONU) to produce the upstream signal. Single side-band (SSB) modulation is used to wavelength-shift the distributed CW carrier, which will be launched into a reflective semiconductor optical amplifier (RSOA) based ONU for directly modulation of 5.15 Gbps OFDM upstream signal. To avoid the radio-frequency (RF) power fading and chromatic fiber dispersion, the four-band OFDM modulation is proposed to generate a 40 Gbps downstream when a Mach-Zehnder modulator (MZM) with -0.7 chirp parameter is used. Hence, the RB circumvention can be centralized in the CO. Moreover, the signal performances of downstream and upstream are also studied and discussed in this measurement. PMID- 27409911 TI - Liquid crystal filled surface plasmon resonance thermometer. AB - A novel surface plasmon resonance (SPR) thermometer based on liquid crystal (LC) filled hollow fiber is demonstrated in this paper. A hollow fiber was internally coated with silver and then filled with LC. The SPR response to temperature was studied using modeling and verified experimentally. The results demonstrated that the refractive index of LC decreases with the increasing temperature and the variation can be detected by the resonance wavelength shift of the plasmon resonance. The temperature sensitivities were 4.72 nm/ degrees C in the temperature range of 20 to 34.5 degrees C and 0.55 nm/ degrees C in the temperature range of 36 to 50 degrees C, At the phase transition temperature between nematic and isotropic phases of the LC, the temperature sensitivity increased by one order of magnitude and a shift of more than 46 nm was observed with only a 1.5 degrees C temperature change. This sensor can be used for temperature monitoring and alarming, and can be extended for other physical parameter measurement. PMID- 27409912 TI - Emission regimes of random lasers with spatially localized feedback. AB - We report the experimental results obtained with a novel architecture for random lasing, in which the active material, free of scatterers, is placed between two large scattering regions. Lasing emission is investigated as a function of the illuminated area of the scattering regions, obtaining typical "resonant" and "non resonant" random lasing spectra, depending on the device geometry. We propose a theoretical approach for the understanding of the observed phenomena, modelling the scattering elements with arbitrary spectral profiles in amplitude and phase and considering strong coupling between lasing modes. Good agreement between experiments and simulation results is obtained. PMID- 27409913 TI - Variable spatial pattern probe based on offset launch of multimode waveguide for optogenetics. AB - We propose and demonstrate experimentally a variable spatial pattern probe based on offset launch at the input facet of multi-mode optical waveguide for the use of optogenetics, which could generate variable spatial patterns with micron scale at the output facet of the waveguide so that the optical stimulating location in the neural tissue can be changed. By using of coupling mode theory, finite element method (FEM) and light diffusion Monte-Carlo method, we simulate their mode patterns and evolvements for TE00, TE10, TE20 and TE11 modes, excited by offset launch at different input point of the probe with core size of 17.8 * 7.8 MUm2, from the output port to 50MUm in the tissue. The experimental chips including array multimode waveguides with different width are fabricated using the Silica-on Silicon processing. We selectively excite TE00, TE10, TE20 and TE11 modes in the waveguide chip with core size of 17.8 * 7.8 MUm2, test their patterns and obtain their evolvements. The experimental results are coincident with the simulation results. PMID- 27409914 TI - Symmetry-dependency of anticrossing phenomena in slab-type photonic crystals. AB - The optical properties of photonic crystals (PhCs) are strongly affected by their spatial symmetry characteristics. We observe anticrossing phenomena for large area slab-type silicon PhCs sandwiched between a glass substrate and air. If a glass superstrate plus an index-matching fluid is added, thus establishing a mirror symmetry in z-direction, the anticrossing disappears. These characteristics are analyzed numerically using a finite-element Maxwell solver, and experimentally using large area samples made by nanoimprint lithography. We further discuss the findings by symmetry considerations. PMID- 27409915 TI - Generation of 33 fs 93.5 W average power pulses from a third-order dispersion managed self-similar fiber amplifier. AB - We report on a high-power third-order dispersion managed amplification system that delivers 33-fs pulses of 93.5 W at a repetition rate of 55 MHz. A pair of grisms are used as the pre-chirper for optimizing the third order dispersion (TOD) to group velocity dispersion (GVD) ratio. Detail experiments show that the use of a grsim pre-chirper significantly enhances the quality of the compressed pulses. We demonstrate that the third order dispersion of both the amplifier and the compressor can be compensated for by the grisms. Furthermore, the nonlinear phase shift introduced by spectral asymmetry during amplification can be restrained. This type of scheme, applied in our experiment, can be used for further development of a high power laser with ultrashort pulse and wide spectrum. PMID- 27409916 TI - Broadband wavelength converters with flattop responses based on cascaded second harmonic generation and difference frequency generation in Bessel-chirped gratings. AB - We investigate ultra-broadband wavelength converters based on cascaded second harmonic generation and difference frequency generation using Bessel-chirped gratings (BCGs) in lithium niobate waveguides, and compare them to the ones using uniform grating and segmented grating, respectively. For the same length and power, the BCGs show broader bandwidth than the other two types of grating. The ripple of the matching response is very small as well. Analysis also shows that almost the same conversion bandwidth and maximum conversion efficiency with tolerant response flatness can be achieved when the manufacturing tolerance of the waveguide length is smaller than 0.1 cm. PMID- 27409917 TI - Short all Tm-doped germanate glass fiber MOPA single-frequency laser at 1.95 MUm. AB - Based on heavily Tm-doped germanate glass fibers (TGFs), a short all-TGF MOPA laser system with uniform core parameters in each stage was demonstrated. An 11.7 W stable single-frequency laser at 1.95 MUm with an optical-to-optical conversion efficiency of 20.4% is obtained from a homemade 31-cm-long double-cladding single mode TGF. The estimated stimulated Brillouin scattering (SBS) threshold of 980 W and the measured relative intensity noise of < -130 dB/Hz for frequencies above 2 MHz are achieved in this MOPA system. Furthermore, the prospect for further power scaling of such short MOPA laser is considered. PMID- 27409918 TI - Analytical source-target mapping method for the design of freeform mirrors generating prescribed 2D intensity distributions. AB - A new source-target mapping for the design of mirrors generating prescribed 2D intensity distributions is proposed. The surface of the mirror implementing the obtained mapping is expressed in an analytical form. Presented simulation results demonstrate high performance of the proposed method. In the case of generation of rectangular and elliptical intensity distributions with angular dimensions from 80 degrees x 20 degrees to 40 degrees x 20 degrees , relative standard error does not exceed 8.5%. The method can be extended to the calculation of refractive optical elements. PMID- 27409919 TI - Compact spectrometer system based on a gradient grating period guided-mode resonance filter. AB - We demonstrate a compact spectrometer system by using a gradient grating period guided-mode resonance filter-mounted on a linear photodetector array-that exhibits spatially dependent resonance characteristics; a specific incident wavelength is reflected such that the underlying array pixels measure minimum intensity. A precalibrated transmission efficiency matrix is used to determine each pixel's transmission efficiency for specific wavelengths. Unknown spectral information can be calculated from the measured intensity. Grating periods of 250 388 nm in 2-nm increments are used in each 100-cycle period. Device length is 2.23 mm. Spectral range of 506-700 nm is measurable with 1-nm resolution. PMID- 27409920 TI - Active stabilization of a fiber-optic two-photon interferometer using continuous optical length control. AB - The practical realization of long-distance entanglement-based quantum communication systems strongly rely on the observation of highly stable quantum interference between correlated single photons. This task must accompany active stabilization of the optical path lengths within the single-photon coherence length. Here, we provide two-step interferometer stabilization methods employing continuous optical length control and experimentally demonstrate two-photon quantum interference using an actively stabilized 6-km-long fiber-optic Hong-Ou Mandel interferometer. The two-step active control techniques are applied for measuring highly stable two-photon interference fringes by scanning the optical path-length difference. The obtained two-photon interference visibilities with and without accidental subtraction are found to be approximately 90.7% and 65.4%, respectively. PMID- 27409921 TI - Design and evaluation of new color-corrected rigid endomicroscopic high NA GRIN objectives with a sub-micron resolution and large field of view. AB - We demonstrate new GRIN-based endomicroscopic objectives for high resolution single photon fluorescence imaging modalities. Two endoscopic optical design approaches are presented in detail utilizing firstly diffractive and secondly refractive optical elements for the color correction in a spectral range from 488 nm to 550 nm. They are compared with their precursor device experimentally and by simulation. Inherent aberrations for off-axis field points could be lowered remarkably compared with the values of the state-of-the-art system by increasing the intrinsic optical complexity but maintaining the outer spatial dimensions. As a result, those presented objectives predict a diffraction-limited imaging of objects up to 300 MUm in diameter with a numerical aperture of 0.8 while keeping an overall outer diameter of the assembly at 1.4 mm. Lastly, confocal fluorescence imaging experiments focus on the comparison between the numerical predicted and the practically achieved quality parameters. PMID- 27409922 TI - Far-field sub-diffraction focusing lens based on binary amplitude-phase mask for linearly polarized light. AB - Planar lenses are attractive photonic devices due to its minimized size and easy to integrate. However, planar lenses designed in traditional ways are restricted by the diffraction limit. They have difficulties in further reducing the focal spot size beyond the diffraction limit. Super-oscillation provides a possible way to solve the problem. However, lenses based on super-oscillation have always been affected by huge sidelobes, which resulted in limited field of view and difficulties in real applications. To address the problem, in the paper, a far field sub-diffraction lens based on binary amplitude-phase mask was demonstrated under illumination of linearly polarized plane wave at wavelength 632.8 nm. The lens realized a long focal length of 148lambda (94 um), and the full width at half maximum of the focal line was 0.406lambda, which was super-oscillatory. More important is that such a flat lens has small sidelobes and wide field of view. Within the measured range of [-132lambda, + 120lambda], the maximum sidelobe observed on the focal plane was less than 22% of the central peak. Such binary amplitude-phase planar lens can also be extended to long focal length far-field sub-diffraction focusing lens for other spectrum ranges. PMID- 27409923 TI - Multi-octave linearized analog photonic link based on a polarization-multiplexing dual-parallel Mach-Zehnder modulator. AB - A multi-octave highly-linear analog photonic link with simultaneous suppression of second-order intermodulation distortion (IMD2) and third-order intermodulation distortion (IMD3) is proposed and demonstrated based on a single integrated polarization-multiplexing dual-parallel Mach-Zehnder modulator (PM-DPMZM). The IMD2 is eliminated by biasing one sub-MZM in each sub-DPMZM at a point close to the maximum transmission point and the other sub-MZM at a point close to the minimum transmission point. The obtained fundamental frequency terms are in phase while the second-order harmonics are complementary when the two outputs of the two sub-MZMs are photodetected. The IMD3 is suppressed by adjusting the RF powers introduced to the two sub-DPMZMs, producing two complementary IMD3 terms when the modulated signals are photodetected. An experiment is carried out. Simultaneous suppression of IMD2 and IMD3 is achieved. The second-order spurious-free dynamic range (SFDR2) and third-order spurious-free dynamic range (SFDR3) are 82 dB.Hz1/2 and 110 dB.Hz2/3, respectively, indicating an improvement of 12 dB in SFDR2 and 13 dB in SFDR3 as compared with the low-biased MZM based analog photonic link, or an improvement of 3 dB in SFDR2 and 16 dB in SFDR3 as compared with the quadrature-biased MZM based photonic link. PMID- 27409924 TI - 8.4mJ, 10kHz, 3.6ns, Nd:YVO4 slab amplifier. AB - A diode-pumped nanosecond eight-pass amplifier with Nd:YVO4 crystal was developed. Combined with the advantages of direct pumped and Innoslab structure, a high energy pulse was obtained by using the wedged multi-folded configuration with two plane mirrors. The 0.4mJ Q-switched seed at the pulse repetition frequency of 10kHz was amplified to 8.4mJ with the pump power of 330W, and the corresponding optical-to-optical efficiency was 29.8%. The M2 factors in the horizontal direction and vertical direction were 1.48 and 1.39, respectively. And no remarkable of ASE was observed. PMID- 27409925 TI - Broadband circularly polarizing dichroism with high efficient plasmonic helical surface. AB - We propose and experimentally demonstrate a broadband and high efficient circularly polarizing dichroism using a simple single-cycle and single-helical plasmonic surface array arranged in square lattice. Two types of helical surface structures (partially or completely covered with a gold film) are investigated. It is shown that the circular polarization dichroism in the mid-IR range (3um - 5um) can reach 80% (when the surface is partially covered with gold) or 65% (when the surface is completely covered with gold) with a single-cycle and single helical surface. Experimental fabrications of the proposed helical plasmonic surface are implemented with direct 3D laser writing followed by electron beam evaporation deposition of gold. The experimental evaluations of the circular polarization dichroism are in excellent agreement with the simulation. The proposed helical surface structure is of advantages of easy-fabrication, high dichroism and scalable to other frequencies as a high efficient broadband circular polarizer. PMID- 27409926 TI - Angle- and polarization-dependent spectral characteristics of circular grating filters. AB - We design and implement one type of guided mode resonance (GMR) circular grating filters (CGFs) on an HfO2-on-silicon platform. Taking advantage of an angle-resolved micro-reflection measurement system, we achieve their incident angle- and polarization-dependent reflection spectra. For normal incident arbitrary linear polarization, a pair of reflection peaks is experimentally observed due to the coexistence of the azimuthal component Ea and the radial component Er of the incident wave electric field (E-field). For oblique incident s-polarization (E-field perpendicular to the incident plane), the peak excited by the Ea component splits into two sub-peaks due to the removal of degeneracy, while that excited by the Er component gradually fades away with the increase of the incident angle. For oblique incident p-polarization (E-field parallel to the incident plane), the spectrum appears to be reversed; that is, the peak corresponding to the Er component gets split while that corresponding to the Ea component gradually disappears when the incident angle increases. Moreover, we experimentally demonstrate the spectral relationships between CGFs and linear grating filters under not only normal incidence but also oblique incidence; these relationships greatly facilitate the spectral design and tailoring of the CGFs. PMID- 27409927 TI - Gigahertz frequency comb offset stabilization based on supercontinuum generation in silicon nitride waveguides. AB - Silicon nitride (Si3N4) waveguides represent a novel photonic platform that is ideally suited for energy efficient and ultrabroadband nonlinear interactions from the visible to the mid-infrared. Chip-based supercontinuum generation in Si3N4 offers a path towards a fully-integrated and highly compact comb source for sensing and time-and frequency metrology applications. We demonstrate the first successful frequency comb offset stabilization that utilizes a Si3N4 waveguide for octave-spanning supercontinuum generation and achieve the lowest integrated residual phase noise of any diode-pumped gigahertz laser comb to date. In addition, we perform a direct comparison to a standard silica photonic crystal fiber (PCF) using the same ultrafast solid-state laser oscillator operating at 1 um. We identify the minimal role of Raman scattering in Si3N4 as a key benefit that allows to overcome the fundamental limitations of silica fibers set by Raman-induced self-frequency shift. PMID- 27409928 TI - Highly nonlinear organic crystal OHQ-T for efficient ultra-broadband terahertz wave generation beyond 10 THz. AB - We report on efficient generation of ultra-broadband terahertz (THz) waves via optical rectification in a novel nonlinear organic crystal with acentric core structure, i.e. 2-(4-hydroxystyryl)-1-methylquinolinium 4-methylbenzenesulfonate (OHQ-T), which possesses an ideal molecular structure leading to a maximized nonlinear optical response for near-infrared-pumped THz wave generation. By systematic studies on wavelength-dependent phase-matching conditions in OHQ-T crystals of different thicknesses we are able to generate coherent THz waves with a high peak-to-peak electric field amplitude of up to 650 kV/cm and an upper cut off frequency beyond 10 THz. High optical-to-THz conversion efficiency of 0.31% is achieved by efficient index matching with a selective pumping at 1300 nm. PMID- 27409929 TI - All-optical switches, unidirectional flow, and logic gates with discrete solitons in waveguide arrays. AB - We propose a mechanism by which a number of useful all-optical operations, such as switches, diodes, and logic gates, can be performed with a single device. An effective potential well is obtained by modulating the coupling between the waveguides through their separations. Depending on the power of a control soliton injected through the potential well, an incoming soliton will either completely transmit or reflect forming a controllable switch. We show that two such switches can work as AND, OR, NAND, and NOR logic gates. Furthermore, the same device may also function as a perfect soliton diode with adjustable polarity. We discuss the feasibility of realising such devices with current experimental setups. PMID- 27409930 TI - Anti-phase reflection coating maximizing the directionality of grating couplers. AB - We present numerical demonstrations that anti-phase reflection coatings (APRCs) on the core layers of grating couplers (GCs) return anti-phase field into the core layers and cancel the downward scattering from the gratings by destructive interference to improve the upward directionality of the GCs while the output power per unit length is reduced. Investigating simplified models of GC, we reveal the effect of APRCs semi-analytically and quantitatively. The APRCs can be combined with other enhancement measures, like deep gratings and backside mirrors, to tailor an appropriate output power per unit length while achieving high upward directionalities cooperatively. PMID- 27409931 TI - 300 W-level, wavelength-widely-tunable, all-fiber integrated thulium-doped fiber laser. AB - A high-power, wavelength-tunable, all-fiber integrated thulium-doped fiber laser (TDFL) at 2 MUm is presented. The TDFL has a compact configuration which only consists of a low power seed oscillator and a stage of fiber power amplifier. The seed oscillator adopts a tunable band-pass filter as the wavelength selective element, matching the gain spectrum of thulium-doped fiber. It can provide ~5 W single-mode seed laser with superb spectral characteristics, and the lasing wavelength is adjustable from 1890 to 2050 nm. The fiber power amplifier provides a total gain of ~17 dB at 2 MUm which boosts the signal power to the 300 W-level. The maximum average power reaches 327.5 W at 1930 nm with the highest slope efficiency of 57.4%. This TDFL can afford >270 W lasing operation over the whole tuning range of 140 nm spanning from 1910 to 2050 nm, together with high spectral quality and power stability. This is the first demonstration, to the best of our knowledge, on an all-fiber integrated wavelength-widely-tunable TDFL at 2 MUm with output power at the 300 W-level. The results are of great interest for many applications. PMID- 27409932 TI - Strong multiphoton absorption properties of one styrylpyridinium salt in a highly polar solvent. AB - Multiphoton absorption (MPA) effects have become useful for real applications as well as conceptual predictions. However, most of organic molecules exhibit small Stokes shift and reduced MPA in the highly polar solvents, which may seriously hinder their related applications. In this work, one styrylpyridinium salt has been synthesized, which exhibits outstanding properties such as bright red fluorescence at the wavelength of 626 nm in a highly polar solvent (DMSO). Importantly, it is noted that the material also exhibits strong two- and three photon absorption action cross-section (delta2PA = 597 GM and delta3PA = 18 * 10-80 cm6?s2?photon-2, respectively), which can be excited in near-infrared (NIR) window I (650-900 nm) and NIR window II (1000-1450 nm). Meanwhile, two-photon in vitro bioimaging and MPA induced optical limiting behavior have been successfully demonstrated based on the chromophore. PMID- 27409933 TI - Transverse circular-polarized Bessel beam generation by inward cylindrical aperture distribution. AB - In this paper the focusing capability of a radiating aperture implementing an inward cylindrical traveling wave tangential electric field distribution directed along a fixed polarization unit vector is investigated. In particular, it is shown that such an aperture distribution generates a non-diffractive Bessel beam whose transverse component (with respect to the normal of the radiating aperture) of the electric field takes the form of a zero-th order Bessel function. As a practical implementation of the theoretical analysis, a circular-polarized Bessel beam launcher, made by a radial parallel plate waveguide loaded with several slot pairs, arranged on a spiral pattern, is designed and optimized. The proposed launcher performance agrees with the theoretical model and exhibits an excellent polarization purity. PMID- 27409934 TI - Rapidly tunable optical parametric oscillator based on aperiodic quasi-phase matching. AB - A new optical parametric oscillator (OPO) architecture with high tuning speed capability is demonstrated. This device exploits the versatility offered by aperiodic quasi-phase matching (QPM) to provide a broad parametric gain spectrum without changing the temperature, angle, or position of the nonlinear crystal. Rapid tuning is then straightforwardly achieved using a fast intracavity spectral filter. This concept is demonstrated here for a picosecond synchronously pumped OPO containing an aperiodically poled MgO-doped LiNbO3 crystal and a rapidly tunable spectral filter based on a diffraction grating. Tuning over 160 nm around 3.86 MUm is achieved at fixed temperature and a fast tuning over 30 nm in 40 MUs is demonstrated. Different configurations are tested and compared. The cavity length detuning is analyzed and discussed. This device is successfully used to detect N2O by absorption. This approach could be generalized to other spectral ranges (e.g., visible) and temporal regimes (e.g., continuous wave or nanosecond). PMID- 27409935 TI - Investigation of mid-infrared second harmonic generation in strained germanium waveguides. AB - In this paper we present a detailed theoretical investigation of second harmonic generation in strained germanium waveguides operating at the mid infrared pump wavelength of 4 MUm. The effective second order susceptibility has been estimated through a multiphysics approach considering the residual stress of the SiNx cladding film. Furthermore, general physical features have been investigated by means of a comparative analysis of SHG performance as a function of input pump power, linear and nonlinear phase mismatching, effective recombination carrier lifetime, and temperature, taking into account both continuous and pulsed regimes. Finally, periodically poled germanium devices have been explored with the aim to improve the SHG efficiency. In the same operative conditions, efficiencies of 0.6% and 0.0018% have been obtained in poled and not poled waveguides, respectively. PMID- 27409936 TI - Laser-induced wavelength-controlled self-assembly of colloidal quasi-resonant quantum dots. AB - Self-assembly of colloidal semiconductor quantum dots controlled solely by laser induced interaction is demonstrated for the first time. Pairs of CdTe nanoparticles are formed under irradiation with nanosecond pulses at wavelengths 555 or 560 nm. Formation of pairs is justified by corresponding changes of absorption spectra. Conditions of the experiment are in excellent agreement with those predicted by the theory of laser-induced dipole-dipole interaction of QDs. The fraction of QDs assembled into pairs is up to 47%. PMID- 27409937 TI - Simulation of polarized optical speckle fields: effects of the observation scale on polarimetry. AB - In this paper, we propose the simulation of polarized speckle fields using the Stokes formalism, which allows the description of partially polarized electromagnetic waves. We define a unique parameter which determines the partial decorrelation of the involved fields, allowing to simulate the polarized speckles produced by all types of scatterers, from simple to multiple scatterers. We validate this model by comparison with experimental measurements. We use that simulation model to study the impact of the imaging device parameters on polarimetric measurements: first we emphasize a limit of resolution on retardance measurements, then we study the spatial depolarization, which appears when an observer is measuring any space-variant polarization map. PMID- 27409938 TI - Inherent temperature compensation of fiber-optic current sensors employing spun highly birefringent fiber. AB - We investigate the various contributions to the temperature dependence of an interferometric fiber-optic current sensor employing spun highly-birefringent sensing fiber, in particular, the contributions from the fiber retarder at the fiber coil entrance, the spun fiber's birefringence, and the Faraday effect. We theoretically and experimentally demonstrate that an appropriately designed retarder inherently compensates the temperature dependence of the fiber birefringence and the Faraday effect. We demonstrate insensitivity to temperature to within +/- 0.2% between -40 and + 85 degrees C. Furthermore, we analyze the influence of the retarder parameters on the linearity of the recovered magneto optic phase shift vs. current and determine a set of parameters that results in a perfectly linear relationship. PMID- 27409939 TI - SNR of swept SLEDs and swept lasers for OCT. AB - A back-to-back comparison of a tunable narrow-band-filtered SLED (TSLED) and a swept laser are made for OCT applications. The two sources are similar in terms of sweep speed, tuning range and coherence length. A fundamental issue with a TSLED is that the RIN is proportional to 1/linewidth, meaning that the longer the coherence length, the higher the RIN and clock jitter. We show that the TSLED has an SNR limit that causes noise streaks at points of high reflection in images. The laser, which is shot noise limited, does not exhibit this effect. We add noise terms proportional to the sample power times reference power to standard swept source SNR expressions to account for the SNR limit. PMID- 27409940 TI - Tunable broadband intense IR pulse generation at non-degenerate wavelengths using group delay compensation in a dual-crystal OPA scheme. AB - A robust group delay compensated dual-crystal optical parametric amplification (DOPA) scheme is proposed that will be used to prove the positive effect of group delay compensation on a DOPA as predicted by the simulations in the previously published literature. Through simple adjustments, it is also capable of providing 20 fs pulses (theoretically compressible to 12 fs, corresponding to sub-four cycle for 1300 nm components), broadband IR pulses at non-degenerate wavelengths using short pulse (broadband) pump laser. In our table-top DOPA system, group delay compensation has been realized using a simple optical crystal. Our design provides output power in order of 100 mW. We managed to achieve minimum 20 nm improvement on the bandwidth, compared to single-crystal OPA (SOPA) structure whilst keeping total conversion efficiency above 30%. Adjusting our configuration by optimizing the phase-matching angles of the two BBO crystals, we also have realized a practical scheme that benefitting from group delay compensation can obtain 75 nm bandwidth improvement while keeping the conversion efficiency constant. This achievement will open the doors to the realm of multiple crystals OPA systems and provide a solution to the imposed limitation on the effective lengths of applicable non-linear crystals and hence limited power gain of such broadband OPA systems. PMID- 27409941 TI - Compact resonant electro-optic modulator using randomness of a photonic crystal waveguide. AB - We fabricate and demonstrate an electro-optic modulator that utilizes the randomness in a photonic crystal waveguide. We exploit a way of using random photonic crystals for device application that involves restricting the area influenced by the randomness. Our random photonic crystal waveguide is in a diffusive regime and the confinement of light is observed only for a W0.98 waveguide (98% of the original width) placed between W1.05 photonic crystal waveguides, where we obtained a transmittance spectrum with an ultra-high Q of 2.4 * 105. A numerical investigation revealed that the experimental yield rate of the appearance of the high-Q confined mode is larger than 80%, by properly designing the length of W0.98. Since the confinement location is predictable, we integrate a p-i-n structure and demonstrate a GHz electro-optic modulation. PMID- 27409942 TI - Jigsaw puzzle metasurface for multiple functions: polarization conversion, anomalous reflection and diffusion. AB - We demonstrate a simple reconfigurable metasurface with multiple functions. Anisotropic tiles are investigated and manufactured as fundamental elements. Then, the tiles are combined in a certain sequence to construct a metasurface. Each of the tiles can be adjusted independently which is like a jigsaw puzzle and the whole metasurface can achieve diverse functions by different layouts. For demonstration purposes, we realize polarization conversion, anomalous reflection and diffusion by a jigsaw puzzle metasurface with 6 * 6 pieces of anisotropic tile. Simulated and measured results prove that our method offers a simple and effective strategy for metasurface design. PMID- 27409943 TI - Phase-shifted Brillouin dynamic gratings using single pump phase-modulation: proof of concept. AB - Two novel phase-shifted Brillouin dynamic gratings (PS-BDGs) are proposed using single pump phase-modulation (SPPM) in a polarization maintaining fiber (PMF) for the first time to our knowledge. Firstly, based on the stimulated Brillouin scattering (SBS), a transient PS-BDG with a 3-dB bandwidth of 354MHz is written by a 2-ns pump1 pulse and a 100-ps pump2 pulse, where the phase of pump1 pulse is shifted with pi from its middle point through phase modulation. Then, with a high repetition rate of 250MHz for both pump pulses, an enhanced PS-BDG with a deep notch depth is obtained and its notch frequency can be easily tuned by changing the phase shift. We demonstrate a proof-of-concept experiment of the transient PS BDG and show the notch frequency changing by tuning the phase shift. The proposed PS-BDGs have important potential applications in microwave photonics, all-optical signal processing and RoF (radio-over-fiber) networks. PMID- 27409944 TI - Cell imaging using GaInAsP semiconductor photoluminescence. AB - We demonstrate label-free imaging of living cells using a GaInAsP semiconductor imaging plate. The photoluminescence (PL) intensity is changed by immersing the semiconductor wafer in different pH solutions and by depositing charged polyelectrolytes on the wafer. Various observations indicate that this phenomenon arises from the radiative and surface recombination rates modified by the Schottky barrier at the charged semiconductor surface. HeLa cancer cells were cultured on the semiconductor, and PL was observed using a near-infrared camera. The semiconductor areas with the cells attached exhibited characteristic PL profiles, which might reflect the attachment and surface condition of the cells, cellular matrix, and other substances. PMID- 27409945 TI - Polarised light sheet tomography. AB - The various benefits of light sheet microscopy have made it a widely used modality for capturing three-dimensional images. It is mostly used for fluorescence imaging, but recently another technique called light sheet tomography solely relying on scattering was presented. The method was successfully applied to imaging of plant roots in transparent soil, but is limited when it comes to more turbid samples. This study presents a polarised light sheet tomography system and its advantages when imaging in highly scattering turbid media. The experimental configuration is guided by Monte Carlo radiation transfer methods, which model the propagation of a polarised light sheet in the sample. Images of both reflecting and absorbing phantoms in a complex collagenous matrix were acquired, and the results for different polarisation configurations are compared. Focus scanning methods were then used to reduce noise and produce three-dimensional reconstructions of absorbing targets. PMID- 27409946 TI - Concept of contrast transfer function for edge illumination x-ray phase-contrast imaging and its comparison with the free-space propagation technique. AB - Previous studies on edge illumination (EI) X-ray phase-contrast imaging (XPCi) have investigated the nature and amplitude of the signal provided by this technique. However, the response of the imaging system to different object spatial frequencies was never explicitly considered and studied. This is required in order to predict the performance of a given EI setup for different classes of objects. To this scope, in the present work we derive analytical expressions for the contrast transfer function of an EI imaging system, using the approximation of near-field regime, and study its dependence upon the main experimental parameters. We then exploit these results to compare the frequency response of an EI system with respect of that of a free-space propagation XPCi one. The results achieved in this work can be useful for predicting the signals obtainable for different types of objects and also as a basis for new retrieval methods. PMID- 27409947 TI - Neural network calibration of a snapshot birefringent Fourier transform spectrometer with periodic phase errors. AB - Systematic phase errors in Fourier transform spectroscopy can severely degrade the calculated spectra. Compensation of these errors is typically accomplished using post-processing techniques, such as Fourier deconvolution, linear unmixing, or iterative solvers. This results in increased computational complexity when reconstructing and calibrating many parallel interference patterns. In this paper, we describe a new method of calibrating a Fourier transform spectrometer based on the use of artificial neural networks (ANNs). In this way, it is demonstrated that a simpler and more straightforward reconstruction process can be achieved at the cost of additional calibration equipment. To this end, we provide a theoretical model for general systematic phase errors in a polarization birefringent interferometer. This is followed by a discussion of our experimental setup and a demonstration of our technique, as applied to data with and without phase error. The technique's utility is then supported by comparison to alternative reconstruction techniques using fast Fourier transforms (FFTs) and linear unmixing. PMID- 27409948 TI - Conversion efficiency limits and bandgap designs for multi-junction solar cells with internal radiative efficiencies below unity. AB - We calculated the conversion-efficiency limit etasc and the optimized subcell bandgap energies of 1 to 5 junction solar cells without and with intermediate reflectors under 1-sun AM1.5G and 1000-sun AM1.5D irradiations, particularly including the impact of internal radiative efficiency (etaint) below unity for realistic subcell materials on the basis of an extended detailed-balance theory. We found that the conversion-efficiency limit etasc significantly drops when the geometric mean etaint* of all subcell etaint in the stack reduces from 1 to 0.1, and that etasc degrades linearly to logetaint* for etaint* below 0.1. For etaint*<0.1 differences in etasc due to additional intermediate reflectors became very small if all subcells are optically thick for sun light. We obtained characteristic optimized bandgap energies, which reflect both etaint* decrease and AM1.5 spectral gaps. These results provide realistic efficiency targets and design principles. PMID- 27409949 TI - Scattered light modulation cancellation method for sub-ppb-level NO2 detection in a LD-excited QEPAS system. AB - A sub-ppb-level nitrogen dioxide (NO2) QEPAS sensor is developed by use of a cost-effective wide stripe laser diode (LD) emitting at 450 nm and a novel background noise suppression method called scattered light modulation cancellation method (SL-MOCAM). The SL-MOCAM is a variant of modulation spectroscopy using two light sources: excitation and balance light sources. The background noise caused by the stray light of the excitation light sources can be eliminated by exposing the QEPAS spectrophone to the modulated balance light. The noise in the LD-excited QEPAS system is investigated in detail and the results shows that > ~90% background noise can be effectively eliminated by the SL-MOCAM. For NO2 detection, a 1sigma detection limit of ~60 ppb is achieved for 1 s integration time and the detection limit can be improved to 0.6 ppb with an integration time of 360 s. Moreover, the SLMOCAM shows a remote working ability in the preliminary investigation. PMID- 27409950 TI - Wind turbine wake visualization and characteristics analysis by Doppler lidar. AB - Wind power generation is growing fast as one of the most promising renewable energy sources that can serve as an alternative to fossil fuel-generated electricity. When the wind turbine generator (WTG) extracts power from the wind, the wake evolves and leads to a considerable reduction in the efficiency of the actual power generation. Furthermore, the wake effect can lead to the increase of turbulence induced fatigue loads that reduce the life time of WTGs. In this work, a pulsed coherent Doppler lidar (PCDL) has been developed and deployed to visualize wind turbine wakes and to characterize the geometry and dynamics of wakes. As compared with the commercial off-the-shelf coherent lidars, the PCDL in this work has higher updating rate of 4 Hz and variable physical spatial resolution from 15 to 60 m, which improves its capability to observation the instantaneous turbulent wind field. The wind speed estimation method from the arc scan technique was evaluated in comparison with wind mast measurements. Field experiments were performed to study the turbulent wind field in the vicinity of operating WTGs in the onshore and offshore wind parks from 2013 to 2015. Techniques based on a single and a dual Doppler lidar were employed for elucidating main features of turbine wakes, including wind velocity deficit, wake dimension, velocity profile, 2D wind vector with resolution of 10 m, turbulence dissipation rate and turbulence intensity under different conditions of surface roughness. The paper shows that the PCDL is a practical tool for wind energy research and will provide a significant basis for wind farm site selection, design and optimization. PMID- 27409951 TI - Sensing atmospheric reactive species using light emitting diode by incoherent broadband cavity enhanced absorption spectroscopy. AB - We overview our recent progress in the developments and applications of light emitting diode-based incoherent broadband cavity enhanced absorption spectroscopy (LED-IBBCEAS) techniques for real-time optical sensing chemically reactive atmospheric species (HONO, NO3, NO2) in intensive campaigns and in atmospheric simulation chamber. New application of optical monitoring of NO3 concentration-time profile for study of the NO3 initiated oxidation process of isoprene in a smog chamber is reported. PMID- 27409952 TI - Post-growth process for flexible CdS/CdTe thin film solar cells with high specific power. AB - We demonstrated a flexible CdS/CdTe thin film solar cell with high specific power of approximately 254 W/kg. A flexible and ultra-light weight CdS/CdTe cell treated with pre-NP etch process exhibited high conversion efficiency of 13.56% in superstrate configuration. Morphological, structural and optical changes of CdS/CdTe thin films were characterized when pre-NP etch step was incorporated to the conventional post-deposition process. Improvement of photovoltaic parameters can be attributed to the removal of the oxide and the formation of Te-rich layer, which benefit the activation process. Pre-NP etched cell maintained their flexibility and performance under the repeated tensile strain of 0.13%. Our method can pave a way for manufacturing flexible CdS/CdTe thin film solar cells with high specific power for mobile and aerospace applications. PMID- 27409953 TI - Light extraction efficiency enhancement of GaN-based blue LEDs based on ITO/ InxO ohmic contacts with microstructure formed by annealing in oxygen. AB - Indium tin oxide (ITO)/ indium oxide (InxO) double layer structure was adopted as the transparent conduction and light scattering function layer to improve the light extraction efficiency of the GaN-based blue LEDs. The double layer structure was first deposited in one run by electron beam evaporation using ITO and Indium as the source respectively, and then annealed in an oxygen environment. This method can fabricate transparent electrode with microstructure and low specific contact resistivity one time free from lithography and etching, which makes the fabrication process simple and at a ower cost. For the 220 nm ITO/ 170 nm InxO double layer sample annealed at 600 degrees C for 15 min in oxygen, measurement results show that its root mean square of roughness of the surface microstructure can be as high as 85.2 nm which introduces the strongest light scattering. Its light transmittance at 450 nm can maintain 92.4%. At the same time, it can realize lower specific contact resistivity with p-InGaN. Compared with the GaN-based blue LEDs with only 220 nm ITO electrode, the light output power of the LEDs with 220 nm ITO/ 170 nm InxO double layer structure can be increased about 58.8%, and working voltage at 20 mA injection current is decreased about 0.23 V due to the enhanced current spreading capability. The light output power improvement is also theoretically convinced by finite difference time domain simulations. PMID- 27409954 TI - Analyses of optical out-coupling of organic light-emitting devices having micromesh indium tin oxide and conducting polymer as composite transparent electrode. AB - We report the characterization and analyses of organic light-emitting devices (OLEDs) using microstructured composite transparent electrodes consisting of the high-index ITO (indium tin oxide) micromesh and the low-index conducting polymer PEDOT: PSS [poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)], that are fabricated by the facile and convenient microsphere lithography and are useful for enhancing light extraction. The rigorous electromagnetic simulation based on the three-dimensional finite-difference time-domain (FDTD) method was conducted to study optical properties and mechanisms in such devices. It provides a different but consistent viewpoint/insight of how this microstructured electrode enhances optical out-coupling of OLEDs, compared to that provided by ray optics simulation in previous works. Both experimental and simulation studies indicate such a microstructured electrode effectively enhances coupling of internal radiation into the substrate, compared to devices with the typical planar ITO electrode. By combining this internal extraction structure and the external extraction scheme (e.g. by attaching extraction lens) to further extract radiation into the substrate, a rather high external quantum efficiency of 46.8% was achieved with green phosphorescent OLEDs, clearly manifesting its high potential. PMID- 27409955 TI - Directionally solidified fabrication in planar geometry of Al2O3-Er3Al5O12 eutectic composite for thermophotovoltaic devices. AB - In this work Al2O3 Er3Al5O12 eutectic composite was manufactured in planar geometry departing from eutectic particles both produced by directional solidification using a CO2 laser system at rates of 180 and 720 mm/h. Microstructure and mechanical properties were investigated as a function of the growth rate. Homogeneous and interpenetrated microstructure was found with phase size strongly dependent on the growth rate, decreasing when the processing rate was increased. Thermal emission of eutectic composites was studied in function of thermal excitation by using CO2 laser radiation as a heating source. An intense narrow emission band at 1.55 um matching with the sensitive region of the InGaAs photoconverter and a low emission band at 1 um were obtained. Features of thermal emission bands were correlated with collecting angle, microstructure and laser power, and compared to those obtained from departing eutectic particles. PMID- 27409956 TI - Omnidirectional, polarization-independent, ultra-broadband metamaterial perfect absorber using field-penetration and reflected-wave-cancellation. AB - In this work, we present the result of nickel (Ni)-based metamaterial perfect absorbers (MPA) with ultra-broadband close-to-one absorbance. The experimental broadband characteristic is significantly improved over the past effort on metamaterial perfect absorbers. An in-depth physical picture and quantitative analysis is presented to reveal the physical origin of its ultrabroadband nature. The key constituent is the cancellation of the reflected wave using ultra-thin, moderate-extinction metallic films. The ultra-thin metal thickness can reduce the reflection as the optical field penetrates through the metallic films. This leads to minimal reflection at each ultra-thin metal layer, and light is penetrating into the Ni/SiO2 stacking. More intuitively, when the layer thickness is much smaller than the photon wavelength, the layer is essentially invisible to the photons. This results in absorption in the metal thin-film through penetration while there is minimal reflection by the metal film. More importantly, the experimental evidence for omni-directionality and polarization insensitivity are established for the proposed design. Detailed measurement is conducted. Due to the ultrathin metal layers and the satisfactory tolerance in dielectric thickness, the broadband absorption has minimal degradation at oblique incidence. Such a wide angle, polarization-insensitive, ultra-broadband MPA can be very promising in the future, and the optical physics using sub-skin-depth metal film can also facilitate miniaturized high-performance nano-photonic devices. PMID- 27409957 TI - Improved impedance characteristics of all-water-processable triple-stacked hole selective layers in solution-processed OLEDs. AB - We herein report an investigation of the device performance capabilities and impedance characteristics of solution-processed organic light-emitting devices (OLEDs) with all-water-processable triple-stacked hole-selective layers (HSLs) on an indium-tin-oxide (ITO) anode, fabricated using a simple coating technique. Highly smooth and homogeneous triple-stacked layers were deposited via horizontal dip- (H-dip-) coating using aqueous dispersions of graphene oxide (GO), molybdenum oxide (MoO3), and poly(ethylenedioxy thiophene):poly(styrene sulfonate) ( PEDOT: PSS). From the triple-stacked GO/MoO3/ PEDOT: PSS HSLs used as hole-injection layers (HILs) in the OLEDs, which outperform a conventional single HIL of PEDOT: PSS, it was found that OLEDs with triple-stacked HILs exhibited characteristic impedance properties, including low parallel resistance with trap-free space-charge-limited conductivity. Furthermore, it was shown that the relaxation frequency of a sample OLED with triple-stacked GO/MoO3/ PEDOT: PSS HILs was much higher than that of a reference device with a single PEDOT: PSS HIL. These impedance behaviors indicate that carrier (hole) injection in the sample OLED is more efficient than that in any of the other devices tested here. The results presented here clarify that the triple-stacked GO/MoO3/ PEDOT: PSS layers can act as efficient HILs on an ITO anode, representing a remarkable advance in relation to the mass production of high-performance solution processable OLEDs. PMID- 27409958 TI - Optical properties of highly polarized InGaN light-emitting diodes modified by plasmonic metallic grating. AB - We implement finite-difference time-domain (FDTD) method to simulate the optical properties of highly polarized InGaN light emitting diodes (LEDs) coupled with metallic grating structure. The Purcell factor (Fp), light extraction efficiency (LEE), internal quantum efficiency (IQE), external quantum efficiency (EQE), and modulation frequency are calculated for different polarized emissions. Our results show that light polarization has a strong impact on Fp and LEE of LEDs due to their coupling effects with the surface plasmons (SPs) generated by metallic grating. Fp as high as 34 and modulation frequency up to 5.4 GHz are obtained for a simulated LED structure. Furthermore, LEE, IQE and EQE can also be enhanced by tuning the coupling between polarized emission and SPs. These results can serve as guidelines for the design and fabrication of high efficiency and high speed LEDs for the applications of solid-state lighting and visible-light communication. PMID- 27409959 TI - Novel and efficient Mie-metamaterial thermal emitter for thermophotovoltaic systems. AB - We theoretically demonstrate a novel, efficient and cost effective thermal emitter using a Mie-resonance metamaterial for thermophotovoltaic (TPV) applications. We propose for the first time the design of a thermal emitter which is based on nanoparticle-embedded thin film. The emitter consists of a thin film of SiO2 on the top of tungsten layer deposited on a substrate. The thin film is embedded with tungsten nanoparticles which alter the refractive index of the film. This gives rise to desired emissive properties in the wavelength range of 0.4 MUm to 2 MUm suitable for GaSb and InGaAs based photovoltaics. Effective dielectric properties are calculated using Maxwell Garnett-Mie theory. Our calculations indicate this would significantly improve the efficiency of TPV cells. We introduce a new parameter to gauge the efficacy of thermal emitters and use it to compare different designs. PMID- 27409960 TI - Chirped laser dispersion spectroscopy for laser-based hydrogen sulfide detection in open-path conditions. AB - In this paper the design and characterization of a near-IR Chirped Laser Dispersion Spectroscopy (CLaDS)-based setup for hydrogen sulfide (H2S) detection is reported. This system can be implemented for open-path sensing also in standoff configuration. Target transition selection, system noise and detection limit are discussed and characterized. Furthermore, the cross interference with other molecules is analyzed. CLaDS-based detection is shown to be highly immune to background carbon dioxide changes, which is a critical issue in accurate open-path sensing of hydrogen sulfide. PMID- 27409961 TI - Dimming curve based on the detectability and acceptability of illuminance differences. AB - In a psychophysical forced-choice experiment, observers' ability to detect illuminance differences was found to be 7.4% of the initial illuminance. When matching the illuminance of one space with another, observers' acceptance of illuminance differences was 17.8% to 19.1%. Lighting control systems with resolutions between 14.8% and 17.7% were found to have greater usability than others. A new approach to step-dimming leverages knowledge of the detectability and acceptability of illuminance differences, as well as usability, to reduce lighting energy consumption. This method can reduce lighting energy consumption more than continuous dimming. PMID- 27409962 TI - Understanding the angle-independent photon harvesting in organic homo-tandem solar cells. AB - The effective device photo current of organic tandem solar cells is independent of the angle of light incidence up to 65 degrees . This feature renders these devices particularly suitable for stationary applications where they receive mainly indirect light. In a combined experimental and simulative study, we develop a fundamental understanding of the causal absorption and charge generation mechanisms in organic homo-tandem solar cells. A 3-terminal tandem device architecture is used to measure the optoelectronic properties of both subcells individually. The analysis of the angle dependent external quantum efficiencies of the subcells and the tandem device reveal an internal balancing of the wavelength dependent subcell currents elucidating the low sensitivity of the tandem device properties on the angle of incidence. PMID- 27409963 TI - Dynamic lighting system for the learning environment: performance of elementary students. AB - This study aims to investigate the effects of lighting color temperatures on elementary students' performance, and thereby propose a dynamic lighting system for a smart learning environment. Three empirical studies were conducted: First, physiological responses were measured as a potential mediator of performance. Second, cognitive and behavioral responses were observed during academic and recess activities. Lastly, the experiment was carried out in a real-life setting with prolonged exposure. With a comprehensive analysis of the three studies, three lighting presets-3500 K, 5000 K, and 6500 K-are suggested for easy, standard, and intensive activity, respectively. The study is expected to act as a good stepping stone for developing dynamic lighting systems to support students' performance in learning environments. PMID- 27409964 TI - Optical characterization of voltage-accelerated degradation in CH3NH3PbI3 perovskite solar cells. AB - We investigate the performance degradation mechanism of CH3NH3PbI3 perovskite solar cells under bias voltage in air and nitrogen atmospheres using photoluminescence and electroluminescence techniques. When applying forward bias, the power conversion efficiency of the solar cells decreased significantly in air, but showed no degradation in nitrogen atmosphere. Time-resolved photoluminescence measurements on these devices revealed that the application of forward bias in air accelerates the generation of non-radiative recombination centers in the perovskite layer buried in the device. We found a negative correlation between the electroluminescence intensity and the injected current intensity in air. The irreversible change of the perovskite grain surface in air initiates the degradation of the perovskite solar cells. PMID- 27409965 TI - Nanophotonic resonators for InP solar cells. AB - We describe high efficiency thin-film InP solar cells that utilize a periodic array of TiO2 nanocylinders. These nanophotonic resonators are found to reduce the solar-weighted average reflectivity of an InP solar cell to ~1.3%, outperforming the best double-layer antireflection coatings. The coupling between Mie scattering resonances and thin-film interference effects accurately describes the optical enhancement provided by the nanocylinders. The spectrally resolved reflectivity and J-V characteristics of the device under AM1.5G illumination are determined via coupled optical and electrical simulations, resulting in a predicted power conversion efficiency > 23%. We conclude that the nanostructured coating reduces reflection without negatively affecting the electronic properties of the InP solar cell by separating the nanostructured optical components from the active layer of the device. PMID- 27409966 TI - Angular distribution of polarized light and its effect on light extraction efficiency in AlGaN deep-ultraviolet light-emitting diodes. AB - Angular distribution of polarized light and its effect on light extraction efficiency (LEE) in AlGaN deep-ultraviolet (DUV) light-emitting diodes (LEDs) are investigated in this paper. A united picture is presented to describe polarized light's emission and propagation processes. It is found that the electron-hole recombinations in AlGaN multiple quantum wells produce three kinds of angularly distributed polarized emissions and propagation process can change their intensity distributions. By investigation the change of angular distributions in 277nm and 215nm LEDs, this work reveals that LEE can be significantly enhanced by modulating the angular distributions of polarized light of DUV LEDs. PMID- 27409967 TI - Development of a tunable diode laser absorption sensor for online monitoring of industrial gas total emissions based on optical scintillation cross-correlation technique. AB - We report the first application of gas total emission using a DFB diode laser for gas concentration measurements combined with two LEDs for gas velocity measurements. In situ gas total emissions and particle density measurements in an industrial pipeline using simultaneous tunable diode laser absorption spectroscopy (TDLAS) and optical scintillation cross-correlation technique (OSCC) are presented. Velocity mean values obtained are 7.59 m/s (OSCC, standard deviation is 1.37 m/s) and 8.20 m/s (Pitot tube, standard deviation is 1.47 m/s) in a steel plant pipeline for comparison. Our experiments demonstrate that the combined system of TDLAS and OSCC provides a new versatile tool for accurate measurements of total gas emissions. PMID- 27409968 TI - Testing different classification methods in airborne hyperspectral imagery processing. AB - To enhance the efficiency of machine-learning algorithms of optical remote sensing imagery processing, optimization techniques are evolved of the land surface objects pattern recognition. Different methods of supervised classification are considered for these purposes, including the metrical classifier operating with Euclidean distance between any points of the multi dimensional feature space given by registered spectra, the K-nearest neighbors classifier based on a majority vote for neighboring pixels of the recognized objects, the Bayesian classifier of statistical decision making, the Support Vector Machine classifier dealing with stable solutions of the mini-max optimization problem and their different modifications. We describe the related techniques applied for selected test regions to compare the listed classifiers. PMID- 27409969 TI - Comparison-based optical study on a point-line-coupling-focus system with linear Fresnel heliostats. AB - Concentrating the concept of a beam-down solar tower with linear Fresnel heliostat (PLCF) is one of the feasible choices and has great potential in reducing spot size and improving optical efficiency. Optical characteristics of a PLCF system with the hyperboloid reflector are introduced and investigated theoretically. Taking into account solar position and optical surface errors, a Monte Carlo ray-tracing (MCRT) analysis model for a PLCF system is developed and applied in a comparison-based study on the optical performance between the PLCF system and the conventional beam-down solar tower system with flat and spherical heliostats. The optimal square facet of linear Fresnel heliostat is also proposed for matching with the 3D-CPC receiver. PMID- 27409970 TI - Optical display film as flexible and light trapping substrate for organic photovoltaics. AB - We demonstrate flexible small molecular solar cells on periodically patterned plastic substrate (LCD display film) using a highly transparent poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) electrode with flexible thin atomic layer deposited (ALD) AlOx top and bottom encapsulation. The organic photovoltaic device (OPV) on this display film shows a power conversion efficiency of 7.48%, which is a 13.0% improvement as compared to a device fabricated on a planar poly-ethylen-terephtalate (PET) substrate (6.62%) and even higher than the efficiency of a device using planar glass substrate (7.15%). The improvement is mainly due to an enhanced harvesting of photons with wavelengths shorter than 500 nm. Moreover, the fully encapsulated device is sufficiently flexible to withstand a bending with a 10 mm radius for more than 50 cycles at ambient condition. These results indicate that the use of standard optical display films is a cheap, simple and efficient way to increase the photocurrent and overall efficiency of organic photovoltaic devices. PMID- 27409971 TI - Feature issue introduction: light, energy and the environment, 2015. AB - The feature issue highlights contributions from authors who presented their research at the OSA Light, Energy and the Environment Congress, held in Suzhou, China from 2 to 5 November, 2015. PMID- 27409972 TI - Routine use of patient reported outcome measures (PROMs) for improving treatment of common mental health disorders in adults. AB - BACKGROUND: Routine outcome monitoring of common mental health disorders (CMHDs), using patient reported outcome measures (PROMs), has been promoted across primary care, psychological therapy and multidisciplinary mental health care settings, but is likely to be costly, given the high prevalence of CMHDs. There has been no systematic review of the use of PROMs in routine outcome monitoring of CMHDs across these three settings. OBJECTIVES: To assess the effects of routine measurement and feedback of the results of PROMs during the management of CMHDs in 1) improving the outcome of CMHDs; and 2) in changing the management of CMHDs. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis group specialised controlled trials register (CCDANCTR-Studies and CCDANCTR References), the Oxford University PROMS Bibliography (2002-5), Ovid PsycINFO, Web of Science, The Cochrane Library, and International trial registries, initially to 30 May 2014, and updated to 18 May 2015. SELECTION CRITERIA: We selected cluster and individually randomised controlled trials (RCTs) including participants with CMHDs aged 18 years and over, in which the results of PROMs were fed back to treating clinicians, or both clinicians and patients. We excluded RCTs in child and adolescent treatment settings, and those in which more than 10% of participants had diagnoses of eating disorders, psychoses, substance use disorders, learning disorders or dementia. DATA COLLECTION AND ANALYSIS: At least two authors independently identified eligible trials, assessed trial quality, and extracted data. We conducted meta-analysis across studies, pooling outcome measures which were sufficiently similar to each other to justify pooling. MAIN RESULTS: We included 17 studies involving 8787 participants: nine in multidisciplinary mental health care, six in psychological therapy settings, and two in primary care. Pooling of outcome data to provide a summary estimate of effect across studies was possible only for those studies using the compound Outcome Questionnaire (OQ-45) or Outcome Rating System (ORS) PROMs, which were all conducted in multidisciplinary mental health care or psychological therapy settings, because both primary care studies identified used single symptom outcome measures, which were not directly comparable to the OQ-45 or ORS.Meta analysis of 12 studies including 3696 participants using these PROMs found no evidence of a difference in outcome in terms of symptoms, between feedback and no feedback groups (standardised mean difference (SMD) -0.07, 95% confidence interval (CI) -0.16 to 0.01; P value = 0.10). The evidence for this comparison was graded as low quality however, as all included studies were considered at high risk of bias, in most cases due to inadequate blinding of assessors and significant attrition at follow-up.Quality of life was reported in only two studies, social functioning in one, and costs in none. Information on adverse events (thoughts of self-harm or suicide) was collected in one study, but differences between arms were not reported.It was not possible to pool data on changes in drug treatment or referrals as only two studies reported these. Meta analysis of seven studies including 2608 participants found no evidence of a difference in management of CMHDs between feedback and no-feedback groups, in terms of the number of treatment sessions received (mean difference (MD) -0.02 sessions, 95% CI -0.42 to 0.39; P value = 0.93). However, the evidence for this comparison was also graded as low quality. AUTHORS' CONCLUSIONS: We found insufficient evidence to support the use of routine outcome monitoring using PROMs in the treatment of CMHDs, in terms of improving patient outcomes or in improving management. The findings are subject to considerable uncertainty however, due to the high risk of bias in the large majority of trials meeting the inclusion criteria, which means further research is very likely to have an important impact on the estimate of effect and is likely to change the estimate. More research of better quality is therefore required, particularly in primary care where most CMHDs are treated.Future research should address issues of blinding of assessors and attrition, and measure a range of relevant symptom outcomes, as well as possible harmful effects of monitoring, health-related quality of life, social functioning, and costs. Studies should include people treated with drugs as well as psychological therapies, and should follow them up for longer than six months. PMID- 27409974 TI - A HaloTag Anchored Ruler for Week-Long Studies of Protein Dynamics. AB - Under physiological conditions, protein oxidation and misfolding occur with very low probability and on long times scales. Single-molecule techniques provide the ability to distinguish between properly folded and damaged proteins that are otherwise masked in ensemble measurements. However, at physiological conditions these rare events occur with a time constant of several hours, inaccessible to current single-molecule approaches. Here we present a magnetic-tweezers-based technique that allows, for the first time, the study of folding of single proteins during week-long experiments. This technique combines HaloTag anchoring, sub-micrometer positioning of magnets, and an active correction of the focal drift. Using this technique and protein L as a molecular template, we generate a magnet law by correlating the distance between the magnet and the measuring paramagnetic bead with unfolding/folding steps. We demonstrate that, using this magnet law, we can accurately measure the dynamics of proteins over a wide range of forces, with minimal dispersion from bead to bead. We also show that the force calibration remains invariant over week-long experiments applied to the same single proteins. The approach demonstrated in this Article opens new, exciting ways to examine proteins on the "human" time scale and establishes magnetic tweezers as a valuable technique to study low-probability events that occur during protein folding under force. PMID- 27409975 TI - Bundle Formation in Biomimetic Hydrogels. AB - Bundling of single polymer chains is a crucial process in the formation of biopolymer network gels that make up the extracellular matrix and the cytoskeleton. This bundled architecture leads to gels with distinctive properties, including a large-pore-size gel formation at very low concentrations and mechanical responsiveness through nonlinear mechanics, properties that are rarely observed in synthetic hydrogels. Using small-angle X-ray scattering (SAXS), we study the bundle formation and hydrogelation process of polyisocyanide gels, a synthetic material that uniquely mimics the structure and mechanics of biogels. We show how the structure of the material changes at the (thermally induced) gelation point and how factors such as concentration and polymer length determine the architecture, and with that, the mechanical properties. The correlation of the gel mechanics and the structural parameters obtained from SAXS experiments is essential in the design of future (synthetic) mimics of biopolymer networks. PMID- 27409973 TI - Glasgow Coma Scale Score in Survivors of Explosion With Possible Traumatic Brain Injury in Need of Neurosurgical Intervention. AB - Importance: Head injury following explosions is common. Rapid identification of patients with severe traumatic brain injury (TBI) in need of neurosurgical intervention is complicated in a situation where multiple casualties are admitted following an explosion. Objective: To evaluate whether Glasgow Coma Scale (GCS) score or the Simplified Motor Score at presentation would identify patients with severe TBI in need of neurosurgical intervention. Design, Setting, and Participants: Analysis of clinical data recorded in the Israel National Trauma Registry of 1081 patients treated following terrorist bombings in the civilian setting between 1998 and 2005. Primary analysis of the data was conducted in 2009, and analysis was completed in 2015. Main Outcomes and Measures: Proportion of patients with TBI in need of neurosurgical intervention per GCS score or Simplified Motor Score. Results: Of 1081 patients (median age, 29 years [range, 0 90 years]; 38.9% women), 198 (18.3%) were diagnosed as having TBI (48 mild and 150 severe). Severe TBI was diagnosed in 48 of 877 patients (5%) with a GCS score of 15 and in 99 of 171 patients (58%) with GCS scores of 3 to 14 (P < .001). In 65 patients with abnormal GCS (38%), no head injury was recorded. Nine of 877 patients (1%) with a GCS score of 15 were in need of a neurosurgical operation, and fewer than 51 of the 171 patients (30%) with GCS scores of 3 to 14 had a neurosurgical operation (P < .001). No difference was found between the proportion of patients in need of neurosurgery with GCS scores of 3 to 8 and those with GCS scores of 9 to 14 (30% vs 27%; P = .83). When the Simplified Motor Score and GCS were compared with respect to their ability to identify patients in need of neurosurgical interventions, no difference was found between the 2 scores. Conclusions and Relevance: Following an explosion in the civilian setting, 65 patients (38%) with GCS scores of 3 to 14 did not experience severe TBI. The proportion of patients with severe TBI and severe TBI in need of a neurosurgical intervention were similar in patients presenting with GCS scores of 3 to 8 and GCS scores of 9 to 14. In this study, GCS and Simplified Motor Score did not help identify patients with severe TBI in need of a neurosurgical intervention. PMID- 27409976 TI - 3D Magnetically Ordered Open Supramolecular Architectures Based on Ferrimagnetic Cu/Adenine/Hydroxide Heptameric Wheels. AB - The present work provides two new examples of supramolecular metal-organic frameworks consisting of three-dimensional extended noncovalent assemblies of wheel-shaped heptanuclear [Cu7(MU-H2O)6(MU3-OH)6(MU-adeninato kappaN3:kappaN9)6](2+) entities. The heptanuclear entity consists of a central [Cu(OH)6](4-) core connected to six additional copper(II) metal centers in a radial and planar arrangement through the hydroxides. It generates a wheel-shaped entity in which water molecules and MU-kappaN3:kappaN9 adeninato ligands bridge the peripheral copper atoms. The magnetic characterization indicates the central copper(II) center is anti-ferromagnetically coupled to external copper(II) centers, which are ferromagnetically coupled among them leading to an S = 5/2 ground state. The packing of these entities is sustained by pi-pi stacking interactions between the adenine nucleobases and by hydrogen bonds established among the hydroxide ligands, sulfate anions, and adenine nucleobases. The sum of both types of supramolecular interactions creates a rigid synthon that in combination with the rigidity of the heptameric entity generates an open supramolecular structure (40-50% of available space) in which additional sulfate and triethylammonium ions are located altogether with solvent molecules. These compounds represent an interesting example of materials combining both porosity and magnetic relevant features. PMID- 27409977 TI - Wafer-Size and Single-Crystal MoSe2 Atomically Thin Films Grown on GaN Substrate for Light Emission and Harvesting. AB - Two-dimensional (2D) atomic-layered semiconductors are important for next generation electronics and optoelectronics. Here, we designed the growth of an MoSe2 atomic layer on a lattice-matched GaN semiconductor substrate. The results demonstrated that the MoSe2 films were less than three atomic layers thick and were single crystalline of MoSe2 over the entire GaN substrate. The ultrathin MoSe2/GaN heterojunction diode demonstrated ~850 nm light emission and could also be used in photovoltaic applications. PMID- 27409978 TI - Vicinal Diamination of Arenes with Domino Aryne Precursors. AB - Vicinal diamination of domino aryne precursors was achieved with sulfamides. The reaction proceeds through a two-aryne pathway, accepting two N-nucleophiles at the 1,2-positions of an arene ring. Symmetrical and unsymmetrical diaminobenzenes were readily obtained. PMID- 27409980 TI - Anomalous Light Emission and Wide Photoluminescence Spectra in Graphene Quantum Dot: Quantum Confinement from Edge Microstructure. AB - The physical origin of the observed anomalous photoluminescence (PL) behavior, that is, the large-size graphene quantum dots (GQDs) exhibiting higher PL energy than the small ones and the broadening PL spectra from deep ultraviolet to near infrared, has been debated for many years. Obviously, it is in conflict with the well-accepted quantum confinement. Here we shed new light on these two notable debates by state-of-the-art first-principles calculations based on many-body perturbation theory. We find that quantum confinement is significant in GQDs with remarkable size-dependent exciton absorption/emission. The edge environment from alkaline to acidic conditions causes a blue shift of the PL peak. Furthermore, carbon vacancies are inclined to assemble at the GQD edge and form the tiny edge microstructures. The bound excitons, localized inside these edge microstructures, determine the anomalous PL behavior (blue and UV emission) of large-size GQDs. The bound excitons confined in the whole GQD lead to the low-energy transition. PMID- 27409979 TI - How Similar Are the Disorders Included Under the Umbrella of Obsessive-Compulsive Disorder and Related Disorders?-Reply. PMID- 27409981 TI - The Delicate Balance of Static and Dynamic Electron Correlation. AB - Multi-configurational approaches yield universal wave function parametrizations that can qualitatively well describe electronic structures along reaction pathways. For quantitative results, multi-reference perturbation theory is required to capture dynamic electron correlation from the otherwise neglected virtual orbitals. Still, the overall accuracy suffers from the finite size and choice of the active orbital space and peculiarities of the perturbation theory. Fortunately, the electronic wave functions at equilibrium structures of reactants and products can often be well described by single-reference methods and hence are accessible to accurate coupled cluster calculations. Here, we calculate the heterolytic double dissociation energy of four 3d-metallocenes with the complete active space self-consistent field method and compare to highly accurate coupled cluster data. Our coupled cluster data are well within the experimental error bars. This accuracy can also be approached by complete active space calculations with an orbital selection based on information entropy measures. The entropy based active space selection is discussed in detail. We find a very subtle balance between static and dynamic electron correlation effects that emphasizes the need for algorithmic active space selection and that differs significantly from restricted active space results for identical active spaces reported in the literature. PMID- 27409982 TI - Assessment of PAXgene Fixation on Preservation of Morphology and Nucleic Acids in Microdissected Retina Tissue. AB - AIM: To compare the effect of the two fixatives on tissue morphology and utility to obtain good quality nucleic acids for molecular analysis from micro-dissected retinal samples. METHODS: Enucleated specimens from New Zealand white rabbits were fixed in formalin or PAXgene fixative according to standard protocols, and then processed and embedded in paraffin for sectioning. Sections were stained with hematoxylin and eosin to assess the structural integrity of retina. Retinal tissue on slides was micro-dissected. DNA/RNA were extracted and assessed for preservation of the quality and quantity of the retinal tissue. RESULTS: The retinal morphology was well preserved with both PAXgene and formalin fixation. The RNA yield obtained using both fixation methods was similar, but RNA from PAXgene fixed paraffin embedded (PFPE) samples had better purity than that from formalin fixed paraffin embedded (FFPE) samples. There was a twofold greater yield of DNA in PFPE compared to FFPE samples but with similar purity. Quantitative reverse transcription PCR analyses showed that the mean cycle threshold values for beta-actin, beta-microglobin, Opsin 1-sw, Rhodopsin, and 18S RNA of the PFPE group were significantly lower than those of the FFPE group (p < 0.01). Greater than 10-fold greater levels of gene expression were detected in PFPE relative to FFPE for the above genes. CONCLUSION: PAXgene fixed tissue retinal morphology is comparable to FFPE tissue. PAXgene may be a good alternative to formalin, providing good tissue morphology and ability to isolate high quality nucleic acids from micro-dissected paraffin embedded retinal samples. PMID- 27409983 TI - Which are the male factors associated with female sexual dysfunction (FSD)? AB - It has been generally assumed that partner's erectile dysfunction, premature, and delayed ejaculation play a significant role in determining female sexual dysfunction (FSD). This study aimed to evaluate the role of the male partner's sexual function, as perceived by women, in determining FSD. A consecutive series of 156 heterosexual women consulting our clinic for FSD was retrospectively studied. All patients underwent a structured interview and completed the Female Sexual Function Index (FSFI). FSFI total score decreased as a function of partner's age, conflicts within the couple, relationship without cohabitation and the habit of engaging in intercourse to please the partner; FSFI total score increased as a function of frequency of intercourse, attempts to conceive and fertility-focused intercourse. FSFI total score showed a negative, stepwise correlation with partner's perceived hypoactive sexual desire (HSD) (r = -0.327; p < 0.0001), whereas no significant correlation was found between FSFI and erectile dysfunction, premature and delayed ejaculation. In an age-adjusted model, partner's HSD was negatively related to FSFI total score (Wald = 9.196, p = 0.002), arousal (Wald = 7.893, p = 0.005), lubrication (Wald = 5.042, p = 0.025), orgasm (Wald = 9.293, p = 0.002), satisfaction (Wald = 12.764, p < 0.0001), and pain (Wald = 6.492, p = 0.011) domains. Partner's HSD was also significantly associated with somatized anxiety, low frequency of intercourse, low partner's care for the patient's sexual pleasure, and with a higher frequency of masturbation, even after adjusting for age. In patients not reporting any reduction in libido, FSFI total score was significantly lower when their partner's libido was low (p = 0.041); the correlation disappeared if the patient also experienced HSD. In conclusion, the presence of erectile dysfunction, premature, and delayed ejaculation of the partner may not act as a primary contributing factor to FSD, as determined by FSFI scores; conversely, women's sexuality seems to be mostly impaired by the perceived reduction in their partner's sexual interest. PMID- 27409984 TI - C-H Coupling Reactions Directed by Sulfoxides: Teaching an Old Functional Group New Tricks. AB - Sulfoxides are classical functional groups for directing the stoichiometric metalation and functionalization of C-H bonds. In recent times, sulfoxides have been given a new lease on life owing to the development of modern synthetic methods that have arisen because of their unique reactivity. They have recently been used in catalytic C-H activation proceeding via coordination of an internal sulfoxide to a metal or through the action of an external sulfoxide ligand. Furthermore, sulfoxides are able to capture nucleophiles and electrophiles to give sulfonium salts, which subsequently enable the formation of C-C bonds at the expense of C-H bonds. This Review summarizes a renaissance period in the application of sulfoxides arising from their versatility in directing C-H functionalization. PMID- 27409985 TI - Enlarged Dural Sac in Idiopathic Bronchiectasis Implicates Heritable Connective Tissue Gene Variants. AB - RATIONALE: Patients with idiopathic bronchiectasis are predominantly female and have an asthenic body morphotype and frequent nontuberculous mycobacterial respiratory infections. They also demonstrate phenotypic features (scoliosis, pectus deformity, mitral valve prolapse) that are commonly seen in individuals with heritable connective tissue disorders. OBJECTIVES: To determine whether lumbar dural sac size is increased in patients with idiopathic bronchiectasis as compared with control subjects, and to assess whether dural sac size is correlated with phenotypic characteristics seen in individuals with heritable connective tissue disorders. METHODS: Two readers blinded to diagnosis measured anterior-posterior and transverse dural sac diameter using L1-L5 magnetic resonance images of 71 patients with idiopathic bronchiectasis, 72 control subjects without lung disease, 29 patients with cystic fibrosis, and 24 patients with Marfan syndrome. We compared groups by pairwise analysis of means, using Tukey's method to adjust for multiple comparisons. Dural sac diameter association with phenotypic and clinical features was also tested. MEASUREMENTS AND MAIN RESULTS: The L1-L5 (average) anterior-posterior dural sac diameter of the idiopathic bronchiectasis group was larger than those of the control group (P < 0.001) and the cystic fibrosis group (P = 0.002). There was a strong correlation between increased dural sac size and the presence of pulmonary nontuberculous mycobacterial infection (P = 0.007) and long fingers (P = 0.003). A trend toward larger dural sac diameter was seen in those with scoliosis (P = 0.130) and those with a family history of idiopathic bronchiectasis (P = 0.149). CONCLUSIONS: Individuals with idiopathic bronchiectasis have an enlarged dural sac diameter, which is associated with pulmonary nontuberculous mycobacterial infection, long fingers, and family history of idiopathic bronchiectasis. These findings support our hypothesis that "idiopathic" bronchiectasis development reflects complex genetic variation in heritable connective tissue and associated transforming growth factor-beta-related pathway genes. PMID- 27409986 TI - Impact of ischaemia time on renal function after partial nephrectomy: a systematic review. AB - OBJECTIVE: To assess the impact of ischaemia on renal function after partial nephrectomy (PN). MATERIALS AND METHODS: A literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. In January 2015, the Medline and Embase databases were systematically searched using the protocol ('warm ischemia'[mesh] OR 'warm ischemia'[ti]) AND ('nephrectomy'[mesh] OR 'partial nephrectomy'[ti]). An updated search was performed in December 2015. Only studies based on a solitary kidney model or on a two-kidney model but with assessment of split renal function were included in this review. RESULTS: Of the 1119 studies identified, 969 abstracts were screened after duplicates were removed: 29 articles were finally included in this review, including nine studies that focused on patients with a solitary kidney. None of the nine studies adjusting for the amount of preserved parenchyma found a negative impact of warm ischaemia time on postoperative renal function, unless this was extended beyond a 25-min threshold. The quality and the quantity of preserved parenchyma appeared to be the main contributors to postoperative renal function. CONCLUSION: Currently, no evidence supports that limited ischaemia time (i.e. <=25 min) has a higher risk of reducing renal function after PN compared to a 'zero ischaemia' technique. Several recent studies have suggested that prolonged warm ischaemia (>25-30 min) could cause an irreversible ischaemic insult to the surgically treated kidney. PMID- 27409987 TI - Association between prenatal care and small for gestational age birth: an ecological study in Quebec, Canada. AB - BACKGROUND: In Quebec, women living on low income receive a number of additional prenatal care visits, determined by their area of residence, of both multi component and food supplementation programs. We investigated whether increasing the number of visits reduces the odds of the main outcome of small for gestational age (SGA) birth (weight < 10th percentile on the Canadian scale). METHODS: In this ecological study, births were identified from Quebec's registry of demographic events between 2006 and 2008 (n = 156 404; 134 areas). Individual characteristics were extracted from the registry, and portraits of the general population were deduced from data on multi-component and food supplement interventions, the Canadian census and the Canadian Community Health Survey. Mothers without a high school diploma were eligible for the programs. Multilevel logistic regression models were fitted using generalized estimating equations to account for the correlation between individuals on the same territory. Potential confounders included sedentary behaviour and cigarette smoking. The odds ratios (ORs) were adjusted for mother's age, marital status, parity, program coverage and mean income in the area. RESULTS: Mothers eligible for the programs remain at a higher odds of SGA than non-eligible mothers (OR = 1.40; 95% confidence interval [CI]: 1.30-1.51). Further, areas that provide more visits to eligible mothers (4-6 food supplementation visits) seem more successful at reducing the frequency of SGA birth than those that provide 1-2 or 3 visits (OR = 0.86; 95% CI: 0.75-0.99). CONCLUSION: Further studies that validate whether an increase in the number of prenatal care interventions reduces the odds of SGA birth in different populations and evaluate other potential benefits for the children should be done. PMID- 27409989 TI - Correction: Status Report - The Canadian Hospitals Injury Reporting and Preventive Program: a dynamic and innovative injury surveillance system. AB - [This corrects the article http://www.phac-aspc.gc.ca/publicat/hpcdp-pspmc/36 6/ar-02-eng.php]. PMID- 27409988 TI - Characteristics of e-cigarette users and their perceptions of the benefits, harms and risks of e-cigarette use: survey results from a convenience sample in Ottawa, Canada. AB - INTRODUCTION: Although e-cigarette use ("vaping") is increasing in Canada, few attempts have been made to describe e-cigarette users ("vapers"). In this context, we conducted a study in Ottawa, Canada, to describe e-cigarette users' perceptions of the benefits, harms and risks of e-cigarettes. We also collected information on why, how and where they use e-cigarettes as well as information on side effects. METHODS: A 24-item online survey was administered to individuals who purchased e-cigarettes or e-cigarette-related supplies at one of Ottawa's 17 e-cigarette shops. Descriptive analyses characterized respondents, and logistic regression models were fitted to evaluate the relationship between respondents' characteristics and their perception of e-cigarette harms. RESULTS: The mean age of the 242 respondents was 38.1 years (range: 16-70 years); 66% were male. Nearly all had smoked 100 or more cigarettes in their lifetime (97.9%). More than 80% indicated that quitting smoking was a very important reason for starting to use e cigarettes and 60% indicated that they intend to stop using e-cigarettes at some point. About 40% reported experiencing some side effects within 2 hours of using e-cigarettes. Those who did not report experiencing any of the listed side effects had approximately 3.2 times higher odds of perceiving e-cigarettes as harmless than those who reported having side effects (odds ratio = 3.17; 95% confidence interval: 1.75-5.73). CONCLUSION: Our findings suggest that most e cigarette users are using them to reduce or stop smoking cigarettes and perceive them as harmless. Due to our use of convenience sampling, the reader should be cautious in generalizing our findings to all Canadian e-cigarette users. PMID- 27409990 TI - In situ crosslinkable elastomeric hydrogel for long-term cell encapsulation for cardiac applications. AB - The regenerative therapy of tissues relays on successful cell transplantation and engraftment. Soft hydrogel carriers are employed to protect transplanted cells from harmful microenvironment in soft tissue regeneration. Herein an injectable, porous, biodegradable, bioresorbable, and elastomeric hydrogel fabricated from poly(propylene fumarate-co-sebacate-co-ethylene glycol) crosslinked with PEGDA for cardiomyoblast encapsulation was reported. The hydrogel retains adequate mechanical property in the range of native myocardium even after 30 days of degradation (49 +/- 0.008 kPa). The hydrogel shows maximum extensibility without collapsing even under 60% compression. The hydrogel retains 70.58% equilibrium water content, wide internal porosity, and slow bulk degradation favorable for cell carriers. The cardiomyoblast cells encapsulated in hydrogel retains viability even after 30 days of culture. The long-term viability and proliferation studies of encapsulated cells in the hydrogel substantiate the suitability of hydrogel microenvironment for cell survival. The present hydrogel is a potential cell carrier with favorable physical and biological properties for cell encapsulation for cardiac applications. The candidate hydrogels perform better than the other reported elastomeric hydrogels fabricated for cell therapy. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2936-2944, 2016. PMID- 27409991 TI - Impact of Urologist Density and County Rurality on the Practice of Retroperitoneal Lymph Node Dissection and Cancer-Specific Death in Patients with Nonseminomatous Germ Cell Tumors. AB - PURPOSE: To investigate the impact of rural status and urologist density on the practice of retroperitoneal lymph node dissection (RPLND) and cancer-specific death (CSD) in patients with nonseminomatous germ cell tumor (NSGCT). METHODS: Urologist density was determined from 2014 to 2015 Area Health Resource File data, and rural residence was determined using the 2003 Rural-Urban Continuum Codes. All cases of NSGCT within Surveillance, Epidemiology and End Results (SEER) 18 with known county code were used for analysis (n = 9473). Fisher's exact test, t-tests, and Cox proportional hazard analysis were used to examine the association between variables of interest and study endpoints. RESULTS: Overall, 26.7% of cases lived in a county with less than the mean urologist density, 6.23% lived in counties with no urologists, 9.0% lived in a rural county, and 23.1% (n = 2208) had RPLND performed. RPLND was performed more in cases who lived in a county with a urologist and more in cases with urban residence (p < 0.05). The mean number of lymph nodes examined was lower in patients who lived in rural counties and counties with fewer urologists (p < 0.05). There was no difference in the number of positive nodes dependent upon either urologist density categorization or rurality (p > 0.05). Rurality and low urologist density were not associated with a higher risk of CSD related to NSGCT. CONCLUSIONS: Patient's residence and access to urologists affect their surgical NSGCT treatment, and efforts aimed at improving access to high-quality RPLND may be indicated. PMID- 27409992 TI - Continuous Production of Carbon-Supported Cubic and Octahedral Platinum-Based Catalysts Using Conveyor Transport System. AB - A conveyor transport system is developed for the continuous production of carbon supported uniform Pt nanocubes, and Pt3 Ni nanocubes and octahedra in a single reaction system under hot carbon monoxide environment. Oleylamine is critical for the high loading and even the dispersion of Pt nanocubes on a carbon support. The metal catalyst shows high performance in electrocatalytic oxidation of methanol. PMID- 27409993 TI - Coming in postgraduate medicine. PMID- 27409994 TI - Problems solutions. PMID- 27409995 TI - What's happening in medicine. PMID- 27409996 TI - Washington Background. PMID- 27409998 TI - Depression and Suicide. PMID- 27409997 TI - National Poison Prevention Week March 16 To 22, 1975 Visual Aids On Poison Prevention. PMID- 27409999 TI - Pediatric Problems. PMID- 27410000 TI - Gastro-Intestinal Problems. PMID- 27410001 TI - From the Assembly Program. PMID- 27410003 TI - Therapeutic Index TO Advertisers. PMID- 27410004 TI - Coming in sportsmedicine. PMID- 27410005 TI - Letters. PMID- 27410006 TI - Scanning sports. PMID- 27410009 TI - Never Buy Another. PMID- 27410011 TI - Brief reports. PMID- 27410010 TI - Liability and Survival. PMID- 27410012 TI - Distance Race Injuries: An Analysis of Runners' Perceptions. AB - In brief: This report examines the type and frequency of self-reported injuries that occurred at the Chicago Distance Classic, a 20km race held each year in July. Questionnaires were sent to the nearly 5,000 entrants. The runners were asked about their medical history and if they had suffered injuries or illnesses from the race. Most entrants had been running two to five years. More than half stretched regularly before and after running. The knee was most often injured (10%), and the foot was second. Most orthopedic, knee, and foot injuries occurred to beginners, and most entrants were between ages 31 and 40. Many of the entrants said they were affected by the heat; 31 said they suffered severely from the heat. PMID- 27410013 TI - How I Manage Travelers' Diarrhea. AB - In brief: On the basis of apparent risk/benefit ratios, the prophylactic use of antibiotics is not recommended for travelers to underdeveloped countries. When visiting certain high- risk areas such as Latin America, Southeast Asia, and Africa, travelers should obtain an antimotility drug or use bismuth subsalicylate for moderate forms of travelers' diarrhea. An antimicrobial agent such as doxycycline, trimethoprim, or trimethoprim-sulfamethoxazole is recommended for more severe travelers' diarrhea. Travelers who have persistent diarrhea with fever, serious fluid loss, or bloody stools should seek medical attention. PMID- 27410014 TI - Arthroscopic Assessment and Treatment of Dancers' Knee Injuries. AB - In brief: The author saw 16 dancers with a history of dance-related knee injuries that had defied conservative treatment. Arthroscopic examination revealed 15 meniscal tears and four cases of chondromalacia patellae. The meniscal tears were treated by partial arthroscopic meniscectomy and the chondromalacia patellae by shaving, drilling, and debridement of the patella. After surgery the results were rated by means of a physical examination and a patient questionnaire. The results were generally excellent, with 13 of the 16 dancers returning to a preoperative level of dance activity. However, the author stresses the importance of preventing injury by using correct dance technique, wearing knee pads during practice, and avoiding excessively hard floor surfaces. PMID- 27410015 TI - Eating Disorders in Young Athletes. AB - In brief: Anorexia nervosa and bulimia are increasingly common in young athletes. In this discussion a physician, a psychiatrist, a dietitian, and three college coaches review the problem and discuss what coaches can do about it. Treatment of eating disorders is much more effective when they are detected early. Coaches need to know the symptoms and potential consequences of these illnesses and are in an excellent position to detect them and to counsel athletes. In their anxiety to win, coaches must be careful of their athletes' overall health and should not encourage them to try crash weight-loss programs, which often lead to eating disorders. PMID- 27410016 TI - Effects of a Rebound Exercise Training Program on Aerobic Capacity and Body Composition. AB - In brief: Training on rebound exercise equipment (minitrampolines) is a popular new approach to aerobic conditioning, but its physiological benefits have been a matter of debate. This study was designed to determine if rebound aerobic dancing is an effective way to improve aerobic capacity and body composition. A group of previously sedentary college women who trained on rebound equipment three times a week for eight weeks showed a 9% increase in max but no significant change in percent body fat. A control group showed no significant changes. The improvement was similar to results produced by conventional aerobic dance programs of like intensity but moderate in comparison to other established forms of aerobic exercise. PMID- 27410017 TI - Pro Hockey Turns to Fitness for a Winning Edge. AB - Time was when professional hockey players played themselves into shape. But in the last several years, extensive fitness testing and year-round conditioning programs-on and off the ice-have become popular. PMID- 27410018 TI - Body Fat Measurement: Weighing the Pros and Cons of Electrical Impedance. AB - Whether for aesthetic, athletic, or medical reasons, more and more people want a convenient and reliable method of measuring body fat. Research technologists have responded to the demand with electrical impedance units; physiologists are busy examining those units. PMID- 27410019 TI - Eating Nutritiously on the Road. PMID- 27410020 TI - Taping a Mallet Finger. PMID- 27410021 TI - Sports Medicine Groups 1985. PMID- 27410022 TI - Abstracts at a glance. PMID- 27410023 TI - What Happened to Old-Fashioned Calisthenics? PMID- 27410025 TI - Conformational flexibility of the complete catalytic domain of Cdc25B phosphatases. AB - Cdc25B phosphatases are involved in cell cycle checkpoints and have become a possible target for developing new anticancer drugs. A more rational design of Cdc25B ligands would benefit from detailed knowledge of its tertiary structure. The conformational flexibility of the C-terminal region of the Cdc25B catalytic domain has been debated recently and suggested to play an important structural role. Here, a combination of experimental NMR measurements and molecular dynamics simulations for the complete catalytic domain of the Cdc25B phosphatase is presented. The stability of the C-terminal alpha-helix is confirmed, but the last 20 residues in the complete catalytic domain are very flexible, partially occlude the active site and may establish transient contacts with the protein core. This flexibility in the C-terminal tail may modulate the molecular recognition of natural substrates and competitive inhibitors by Cdc25B. Proteins 2016; 84:1567 1575. (c) 2016 Wiley Periodicals, Inc. PMID- 27410026 TI - From condemnation to normalisation: Young Africans' narratives about same-sex attraction and implications for communication and advocacy efforts. AB - Narrative is a primary tool in human meaning-making and communication. Frequently value-laden, it plays an important role in global public health communication and advocacy efforts. State-endorsed homophobia is widespread across much of sub Saharan Africa, severely restricting access to sexual health services and undermining human rights and mental health for sexual minorities. Young Africans' narratives about same-sex attraction (SSA) can both inform message framing and provide a source of creative ideas for communication and advocacy efforts. We conducted an analysis of 56 narratives about SSA submitted by young people aged 13-24 years from 10 African countries to a spring 2013 scriptwriting competition in response to a prompt inviting participants to 'Tell a story about someone who is attracted to people of the same sex.' We categorised the narratives across a spectrum of attitudinal perspectives vis-a-vis SSA and identified characteristics of each category, ranging from condemnation (including characterising SSA as satanic), through ambivalence (e.g. 'love the sinner, hate the sin'), to acceptance, activism (including petitioning for same-sex marriage), and normalisation. The texts shed light on potential message frames and cultural narratives that can be countered or leveraged in communication efforts to improve the health and human rights of sexual minority Africans. PMID- 27410027 TI - Structural Interpretation of Metastable States in Myoglobin-NO. AB - Nitric oxide binding and unbinding from myoglobin (Mb) is central to the function of the protein. By using reactive molecular dynamics (MD) simulations, the dynamics following NO dissociation were characterized in both time and space. Ligand rebinding can be described by two processes on the 10 ps and 100 ps timescale, which agrees with recent optical and X-ray absorption experiments. Explicitly including the iron out-of-plane (Fe-oop) coordinate is essential for a meaningful interpretation of the data. The proposed existence of an "Fe-oop/NO bound" state is confirmed and assigned to NO at a distance of approximately 3 A away from the iron atom. However, calculated XANES spectra suggest that it is diffcult to distinguish between NO close to the heme-Fe and positions further away in the primary site. Another elusive state, with Fe-ON coordination, was not observed experimentally because it is masked by the energetically more favorable but dissociative (4) A state in this region, which makes the Fe-ON local minimum unobservable in wild-type Mb. However, suitable active-site mutations may stabilize this state. PMID- 27410028 TI - Comparative clinicopathological study of biliary intraductal papillary neoplasms and papillary cholangiocarcinomas. AB - AIMS: The aim of this study was to achieve a better definition of intraductal papillary neoplasms of the bile duct (IPNBs). METHODS AND RESULTS: Biliary tumours that showed predominantly intraductal papillary growth were provisionally classified as IPNBs (n = 25) and papillary cholangiocarcinomas (n = 27). IPNB was defined as a neoplasm that is confined to the epithelium or is regularly arranged in a high-papillary architecture along thin fibrovascular stalks, whereas the term 'papillary cholangiocarcinoma' was used for tumours with more complex papillary structures (e.g. irregular papillary branching or mixed with solid tubular growth). In our consecutive cohort of biliary neoplasms, 5% were classified as IPNBs, and 10% as papillary cholangiocarcinomas. IPNBs differed from papillary cholangiocarcinomas by less advanced invasion, gross mucin overproduction (72% versus 7%), and their prevalent location (84% of IPNBs in intrahepatic/hilar ducts; 70% of papillary cholangiocarcinomas in extrahepatic ducts). Gastric-type and oncocytic-type tumours were only detected in IPNBs. Expression of mucin core proteins and cytokeratin 20 significantly differed between the two groups. KRAS and GNAS were wild-type genotypes in all but one case of KRAS-mutated IPNB. Patients with IPNB had better recurrence-free survival than those with papillary cholangiocarcinoma (P = 0.007). In multivariate analysis, in which several other prognostic factors (e.g. stromal invasion and lymph node metastasis) were applied, the classification of the two papillary tumours was an independent prognostic factor (P = 0.040). CONCLUSIONS: Given the significant contrast in clinicopathological features between IPNBs and papillary cholangiocarcinomas, it may be more appropriate to use the diagnostic term 'IPNB' for selected tumours that show regular papillary growth, separately from papillary cholangiocarcinomas. PMID- 27410029 TI - Temporal Decay in Timber Species Composition and Value in Amazonian Logging Concessions. AB - Throughout human history, slow-renewal biological resource populations have been predictably overexploited, often to the point of economic extinction. We assess whether and how this has occurred with timber resources in the Brazilian Amazon. The asynchronous advance of industrial-scale logging frontiers has left regional scale forest landscapes with varying histories of logging. Initial harvests in unlogged forests can be highly selective, targeting slow-growing, high-grade, shade-tolerant hardwood species, while later harvests tend to focus on fast growing, light-wooded, long-lived pioneer trees. Brazil accounts for 85% of all native neotropical forest roundlog production, and the State of Para for almost half of all timber production in Brazilian Amazonia, the largest old-growth tropical timber reserve controlled by any country. Yet the degree to which timber harvests beyond the first-cut can be financially profitable or demographically sustainable remains poorly understood. Here, we use data on legally planned logging of ~17.3 million cubic meters of timber across 314 species extracted from 824 authorized harvest areas in private and community-owned forests, 446 of which reported volumetric composition data by timber species. We document patterns of timber extraction by volume, species composition, and monetary value along aging eastern Amazonian logging frontiers, which are then explained on the basis of historical and environmental variables. Generalized linear models indicate that relatively recent logging operations farthest from heavy-traffic roads are the most selective, concentrating gross revenues on few high-value species. We find no evidence that the post-logging timber species composition and total value of forest stands recovers beyond the first-cut, suggesting that the commercially most valuable timber species become predictably rare or economically extinct in old logging frontiers. In avoiding even more destructive land-use patterns, managing yields of selectively-logged forests is crucial for the long-term integrity of forest biodiversity and financial viability of local industries. The logging history of eastern Amazonian old-growth forests likely mirrors unsustainable patterns of timber depletion over time in Brazil and other tropical countries. PMID- 27410030 TI - Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore) Cattle Are Modulators of Growth. AB - Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene Based Test for Genome-wide Association Studies (VEGAS), were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore) cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV) for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1) as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1), IGF2 (insulin like growth factor 2), GH1 (growth hormone 1), IGF1R (insulin like growth factor 1 receptor) and GHR (growth hormone receptor), suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway. PMID- 27410031 TI - Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter. AB - BACKGROUND: Twitter has become the "wild-west" of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, "kid-friendly" flavors, algorithmically generated false testimonials, and free samples. METHODS: All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets) were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching. RESULTS: The overwhelming majority (80%) of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013), up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human) classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014) due to a relative increase in the negative words 'ban', 'tobacco', 'doesn't', 'drug', 'against', 'poison', 'tax' and a relative decrease in the positive words like 'haha', 'good', 'cool'. Automated tweets are more positive than organic (6.17 versus 5.84) due to a relative increase in the marketing words like 'best', 'win', 'buy', 'sale', 'health', 'discount' and a relative decrease in negative words like 'bad', 'hate', 'stupid', 'don't'. CONCLUSIONS: Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media marketing. PMID- 27410032 TI - Interactive Effects of Elevated [CO2] and Drought on the Maize Phytochemical Defense Response against Mycotoxigenic Fusarium verticillioides. AB - Changes in climate due to rising atmospheric carbon dioxide concentration ([CO2]) are predicted to intensify episodes of drought, but our understanding of how these combined conditions will influence crop-pathogen interactions is limited. We recently demonstrated that elevated [CO2] alone enhances maize susceptibility to the mycotoxigenic pathogen, Fusarium verticillioides (Fv) but fumonisin levels remain unaffected. In this study we show that maize simultaneously exposed to elevated [CO2] and drought are even more susceptible to Fv proliferation and also prone to higher levels of fumonisin contamination. Despite the increase in fumonisin levels, the amount of fumonisin produced in relation to pathogen biomass remained lower than corresponding plants grown at ambient [CO2]. Therefore, the increase in fumonisin contamination was likely due to even greater pathogen biomass rather than an increase in host-derived stimulants. Drought did not negate the compromising effects of elevated [CO2] on the accumulation of maize phytohormones and metabolites. However, since elevated [CO2] does not influence the drought-induced accumulation of abscisic acid (ABA) or root terpenoid phytoalexins, the effects elevated [CO2] are negated belowground, but the stifled defense response aboveground may be a consequence of resource redirection to the roots. PMID- 27410033 TI - Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Ki-67 is an established marker of cell proliferation, and the Ki-67 index correlates with the clinical course of several cancer types, including bladder cancer (BC). However, the clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. Therefore, we performed a systematic review and meta-analysis to clarify this relationship. METHODS: A comprehensive literature search for relevant studies published up to February 1, 2016, was performed using PubMed, Cochrane Library, Embase and ISI Web of Knowledge. The effects of Ki-67 expression on survival outcome in patients with BC and BC subtypes were evaluated. Furthermore, the relationship between Ki-67 expression and the clinicopathological features of BC were assessed. RESULTS: Thirty-one studies with 5147 bladder cancer patients were selected for evaluation. Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% CI: 1.33-2.14), progression-free (HR 1.89, 95% CI: 1.43-2.51), overall (HR 2.03, 95% CI: 1.31-3.16), and cancer-specific (HR 1.69, 95% CI: 1.47-1.95) survival. Moreover, whereas high expression was more common in high tumor stage, recurrence status, tumor size, there was no correlation between high Ki-67 expression and age, gender, smoking habits, and tumor number. Importantly, analysis of the different subgroups of BC suggested that significant correlations between high Ki-67 expression and survival outcome (recurrence-free/progression free/overall/cancer-specific survival) are present only in European-American patients. CONCLUSION: The present results indicate that over-expression of Ki-67 is distinctly correlated with poor patient survival. Ki-67 may serve as a valuable biomarker for prognosis in BC patients, particularly in non-Asian BC patients. The results suggest no significant association between Ki-67 expression and BC prognosis in Asian patients. Further efforts are needed to fully clarify this relationship. PMID- 27410035 TI - An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition. AB - B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition. PMID- 27410036 TI - Cloning and Heterologous Expression of the Grecocycline Biosynthetic Gene Cluster. AB - Transformation-associated recombination (TAR) in yeast is a rapid and inexpensive method for cloning and assembly of large DNA fragments, which relies on natural homologous recombination. Two vectors, based on p15a and F-factor replicons that can be maintained in yeast, E. coli and streptomycetes have been constructed. These vectors have been successfully employed for assembly of the grecocycline biosynthetic gene cluster from Streptomyces sp. Acta 1362. Fragments of the cluster were obtained by PCR and transformed together with the "capture" vector into the yeast cells, yielding a construct carrying the entire gene cluster. The obtained construct was heterologously expressed in S. albus J1074, yielding several grecocycline congeners. Grecocyclines have unique structural moieties such as a dissacharide side chain, an additional amino sugar at the C-5 position and a thiol group. Enzymes from this pathway may be used for the derivatization of known active angucyclines in order to improve their desired biological properties. PMID- 27410037 TI - Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice. AB - BACKGROUND: The response of hepatocellular carcinoma (HCC) to immunotherapy is often disappointing and new strategies are clearly needed. The aim of the present study was to investigate whether cytokine-induced killer (CIK) cells combined with a dendritic cell vaccination enhanced cytotoxicity against hepatocarcinoma tumor cells in an in vivo animal model. METHODS: CIKs and DCs were prepared from C3H/HeJ mice by conventional methods, the dendritic cell (DC) pulsed with a MH134 cell lysate, DC or CIK alone were used as controls. Cell phenotypes were analyzed by flow cytometry, cytokine secretion levels were determined by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was assessed by means of an in vitro lactate dehydrogenase (LDH) release assay. A mouse hepatocarcinoma cell MH134-bearing mice model was established to test the in vivo anti-tumor efficacy of the system. RESULTS: CIK cells combined with DC therapy resulted in significant inhibition of tumor growth compared with the control group, whereas the decrease in tumor growth in mice that had been treated with CIK or DC alone did not reach the level of statistical significance. The combination therapy led to a further increase in the population of cytotoxic T cells (CTLs) in vivo, compared to the CIK or DC alone therapy. In addition, the combination therapy significantly enhanced cytotoxic activity against MH134 cells. CONCLUSION: Taken together, these results show that a DC + CIK vaccination is more effective than DC or CIK alone therapy for the treatment of hepatocarcinoma cancer. PMID- 27410038 TI - Detection of JAK2 Exon 12 Mutations in JAK2 V617F-Negative Polycythemia Vera Patients by Cloning Technique. AB - INTRODUCTION: The identification of mutations of the JAK2 gene is a useful marker in the diagnosis of polycythemia vera (PV) patients. We studied the frequency of JAK2 mutations in a group of PV patients because data are still very limited regarding this subject in Polish patients. METHODS: The JAK2 V617F mutation was examined using the amplification refractory mutation system (ARMS)-PCR method. Direct sequencing and a cloning technique were performed to determine alternations in exon 12 of the JAK2 gene. RESULTS: A group of 90 consecutive patients with a suspected diagnosis of polycythemia vera were investigated. In 91% of the cases, the JAK2 V617F mutation was identified. The remaining JAK2 V617F-negative patients were subjected to examination for JAK2 exon 12 by direct PCR product sequencing and the cloning technique. The following mutations were identified: H538-K539delinsL, E543-D544del and N542-E543del. These exon 12 mutants constituted 50% of PV JAK2 V617F-negative group and 4.4% (out of 90) of all PV patients (JAK2 V617F-positive and JAK2 V617F-negative). CONCLUSION: Our results demonstrate the prevalence of JAK2 mutations (V617F and in exon 12) in PV cases. Moreover, the data show that direct sequencing is not an adequate technique for exon 12 mutation identification; therefore, appropriate methodology should be considered for using this molecular marker in the process of diagnosis. PMID- 27410039 TI - Geographic Distribution of Leishmania Species in Ecuador Based on the Cytochrome B Gene Sequence Analysis. AB - A countrywide epidemiological study was performed to elucidate the current geographic distribution of causative species of cutaneous leishmaniasis (CL) in Ecuador by using FTA card-spotted samples and smear slides as DNA sources. Putative Leishmania in 165 samples collected from patients with CL in 16 provinces of Ecuador were examined at the species level based on the cytochrome b gene sequence analysis. Of these, 125 samples were successfully identified as Leishmania (Viannia) guyanensis, L. (V.) braziliensis, L. (V.) naiffi, L. (V.) lainsoni, and L. (Leishmania) mexicana. Two dominant species, L. (V.) guyanensis and L. (V.) braziliensis, were widely distributed in Pacific coast subtropical and Amazonian tropical areas, respectively. Recently reported L. (V.) naiffi and L. (V.) lainsoni were identified in Amazonian areas, and L. (L.) mexicana was identified in an Andean highland area. Importantly, the present study demonstrated that cases of L. (V.) braziliensis infection are increasing in Pacific coast areas. PMID- 27410040 TI - Protecting patient privacy when sharing patient-level data from clinical trials. AB - BACKGROUND: Greater transparency and, in particular, sharing of patient-level data for further scientific research is an increasingly important topic for the pharmaceutical industry and other organisations who sponsor and conduct clinical trials as well as generally in the interests of patients participating in studies. A concern remains, however, over how to appropriately prepare and share clinical trial data with third party researchers, whilst maintaining patient confidentiality. Clinical trial datasets contain very detailed information on each participant. Risk to patient privacy can be mitigated by data reduction techniques. However, retention of data utility is important in order to allow meaningful scientific research. In addition, for clinical trial data, an excessive application of such techniques may pose a public health risk if misleading results are produced. After considering existing guidance, this article makes recommendations with the aim of promoting an approach that balances data utility and privacy risk and is applicable across clinical trial data holders. DISCUSSION: Our key recommendations are as follows: 1. Data anonymisation/de-identification: Data holders are responsible for generating de identified datasets which are intended to offer increased protection for patient privacy through masking or generalisation of direct and some indirect identifiers. 2. Controlled access to data, including use of a data sharing agreement: A legally binding data sharing agreement should be in place, including agreements not to download or further share data and not to attempt to seek to identify patients. Appropriate levels of security should be used for transferring data or providing access; one solution is use of a secure 'locked box' system which provides additional safeguards. This article provides recommendations on best practices to de-identify/anonymise clinical trial data for sharing with third-party researchers, as well as controlled access to data and data sharing agreements. The recommendations are applicable to all clinical trial data holders. Further work will be needed to identify and evaluate competing possibilities as regulations, attitudes to risk and technologies evolve. PMID- 27410041 TI - Erratum. AB - [This corrects the article DOI: 10.1016/S0377-1237(10)80053-X.]. PMID- 27410042 TI - Composite 3D-printed metastructures for low-frequency and broadband vibration absorption. AB - Architected materials that control elastic wave propagation are essential in vibration mitigation and sound attenuation. Phononic crystals and acoustic metamaterials use band-gap engineering to forbid certain frequencies from propagating through a material. However, existing solutions are limited in the low-frequency regimes and in their bandwidth of operation because they require impractical sizes and masses. Here, we present a class of materials (labeled elastic metastructures) that supports the formation of wide and low-frequency band gaps, while simultaneously reducing their global mass. To achieve these properties, the metastructures combine local resonances with structural modes of a periodic architected lattice. Whereas the band gaps in these metastructures are induced by Bragg scattering mechanisms, their key feature is that the band-gap size and frequency range can be controlled and broadened through local resonances, which are linked to changes in the lattice geometry. We demonstrate these principles experimentally, using advanced additive manufacturing methods, and inform our designs using finite-element simulations. This design strategy has a broad range of applications, including control of structural vibrations, noise, and shock mitigation. PMID- 27410043 TI - Allosteric proteins as logarithmic sensors. AB - Many sensory systems, from vision and hearing in animals to signal transduction in cells, respond to fold changes in signal relative to background. Responding to fold change requires that the system senses signal on a logarithmic scale, responding identically to a change in signal level from 1 to 3, or from 10 to 30. It is an ongoing search in the field to understand the ways in which a logarithmic sensor can be implemented at the molecular level. In this work, we present evidence that logarithmic sensing can be implemented with a single protein, by means of allosteric regulation. Specifically, we find that mathematical models show that allosteric proteins can respond to stimuli on a logarithmic scale. Next, we present evidence from measurements in the literature that some allosteric proteins do operate in a parameter regime that permits logarithmic sensing. Finally, we present examples suggesting that allosteric proteins are indeed used in this capacity: allosteric proteins play a prominent role in systems where fold-change detection has been proposed. This finding suggests a role as logarithmic sensors for the many allosteric proteins across diverse biological processes. PMID- 27410044 TI - Soluto-inertial phenomena: Designing long-range, long-lasting, surface-specific interactions in suspensions. AB - Equilibrium interactions between particles in aqueous suspensions are limited to distances less than 1 MUm. Here, we describe a versatile concept to design and engineer nonequilibrium interactions whose magnitude and direction depends on the surface chemistry of the suspended particles, and whose range may extend over hundreds of microns and last thousands of seconds. The mechanism described here relies on diffusiophoresis, in which suspended particles migrate in response to gradients in solution. Three ingredients are involved: a soluto-inertial "beacon" designed to emit a steady flux of solute over long time scales; suspended particles that migrate in response to the solute flux; and the solute itself, which mediates the interaction. We demonstrate soluto-inertial interactions that extend for nearly half a millimeter and last for tens of minutes, and which are attractive or repulsive, depending on the surface chemistry of the suspended particles. Experiments agree quantitatively with scaling arguments and numerical computations, confirming the basic phenomenon, revealing design strategies, and suggesting a broad set of new possibilities for the manipulation and control of suspended particles. PMID- 27410047 TI - Intracranial dissection of word reading mechanisms. PMID- 27410045 TI - Formation and emission of large furans and oxygenated hydrocarbons from flames. AB - Many oxygenated hydrocarbon species formed during combustion, such as furans, are highly toxic and detrimental to human health and the environment. These species may also increase the hygroscopicity of soot and strongly influence the effects of soot on regional and global climate. However, large furans and associated oxygenated species have not previously been observed in flames, and their formation mechanism and interplay with polycyclic aromatic hydrocarbons (PAHs) are poorly understood. We report on a synergistic computational and experimental effort that elucidates the formation of oxygen-embedded compounds, such as furans and other oxygenated hydrocarbons, during the combustion of hydrocarbon fuels. We used ab initio and probabilistic computational techniques to identify low-barrier reaction mechanisms for the formation of large furans and other oxygenated hydrocarbons. We used vacuum-UV photoionization aerosol mass spectrometry and X ray photoelectron spectroscopy to confirm these predictions. We show that furans are produced in the high-temperature regions of hydrocarbon flames, where they remarkably survive and become the main functional group of oxygenates that incorporate into incipient soot. In controlled flame studies, we discovered ~100 oxygenated species previously unaccounted for. We found that large alcohols and enols act as precursors to furans, leading to incorporation of oxygen into the carbon skeletons of PAHs. Our results depart dramatically from the crude chemistry of carbon- and oxygen-containing molecules previously considered in hydrocarbon formation and oxidation models and spearhead the emerging understanding of the oxidation chemistry that is critical, for example, to control emissions of toxic and carcinogenic combustion by-products, which also greatly affect global warming. PMID- 27410046 TI - Clues to NPC1-mediated cholesterol export from lysosomes. PMID- 27410048 TI - Harnessing shared antigens and T-cell receptors in cancer: Opportunities and challenges. PMID- 27410050 TI - Assessment of indoor HONO formation mechanisms based on in situ measurements and modeling. AB - The photolysis of HONO has been found to be the oxidation driver through OH formation in the indoor air measurement campaign SURFin, an extensive campaign carried out in July 2012 in a classroom in Marseille. In this study, the INCA Indoor model is used to evaluate different HONO formation mechanisms that have been used previously in indoor air quality models. In order to avoid biases in the results due to the uncertainty in rate constants, those parameters were adjusted to fit one representative day of the SURFin campaign. Then, the mechanisms have been tested with the optimized parameters against other experiments carried out during the SURFin campaign. Based on the observations and these findings, we propose a new mechanism incorporating sorption of NO2 onto surfaces with possible saturation of these surfaces. This mechanism is able to better reproduce the experimental profiles over a large range of conditions. PMID- 27410049 TI - Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model. AB - PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis. PMID- 27410051 TI - Effects of Instructor Attractiveness on Learning. AB - Although a considerable body of research has examined the impact of student attractiveness on instructors, little attention has been given to the influence of instructor attractiveness on students. This study tested the hypothesis that persons would perform significantly better on a learning task when they perceived their instructor to be high in physical attractiveness. To test the hypothesis, participants listened to an audio lecture while viewing a photograph of instructor. The photograph depicted either a physically attractive instructor or a less attractive instructor. Following the lecture, participants completed a forced choice recognition task covering material from the lecture. Consistent with the predictions; attractive instructors were associated with more learning. Finally, we replicated previous findings demonstrating the role attractiveness plays in person perception. PMID- 27410052 TI - Skills of Cognitive Flexibility in Monolingual and Bilingual Younger Adults. AB - The current study examined skills of cognitive flexibility and sustained attention in late bilingual and monolingual younger adults. One-hundred and sixty two younger adults aged between 18 and 34 years old (M = 22.39) classified as Turkish-English late bilinguals (N = 74) and Turkish monolinguals (N = 88) completed the Trail Making Test (TMT-A and TMT-B). Results from this study showed that Turkish-English late bilinguals had shorter RTs than Turkish monolinguals on the TMT-B, however there were no significant RT differences between the groups on the TMT-A. These findings indicate that bilingualism impacts upon skills of cognitive flexibility but not sustained attention and that the amount of practice in coordinating, monitoring, and switching between languages is an important determinant of cognitive improvement. PMID- 27410053 TI - Measures of Bayesian Reasoning Performance on 'Normal' and 'Natural' Frequency Tasks. AB - While the majority of similar studies examining Bayesian reasoning investigate how participants avoid common errors such as base-rate neglect, the current research also examines whether different formats (frequency and probability) lead to a difference in levels of absolute accuracy. In Study One, older (>=60 years) and younger (18 to 29 years) participants completed tasks in probability and normalized frequency formats. In Study 2, participants completed tasks in probability and natural frequency formats. Findings are that frequencies lead to less over-estimation, particularly in natural frequency tasks, which also reveal an interaction between age and task format whereby older adults seem unaffected by format. There was no association found between format and the avoidance of errors such as base-rate neglect. Findings are discussed in the light of dual and multi-process theories of reasoning, having failed to support the theory that frequency formats elicit System 2 reasoning processes. PMID- 27410054 TI - While We Wait for Life, Life Passes: The Time Metaphors Questionnaire-Short Form. AB - The aim of the present study was to develop a short version of the Time Metaphors Questionnaire (TMQ; Sobol-Kwapinska & Nosal, 2009 ). The original TMQ consists of 95 items and was designed to measure time conceiving. Because completing the TMQ is very time-consuming, this research develops a short form of this questionnaire Time Metaphors Questionnaire-Short Form (TMQ-SF). A sample of 990 Polish adults completed the TMQ. One-half of the sample was used to construct the TMQ-SF by selecting items based on the exploratory factor analysis. The other half of the sample was used to cross-validate the factorial structure of the TMQ-SF by means of confirmatory factor analysis. The TMQ-SF presented high internal consistency and a clear three-factor structure. The convergent and discriminant validity were assessed based on comparison with the Big Five factors of personality, satisfaction with life, positive and negative affect, time perspective, and mindfulness. PMID- 27410055 TI - Corrigendum. PMID- 27410056 TI - Age-Related Macular Degeneration and Its Risk Factors in North Africans Living in Algeria and Italy. AB - PURPOSE: To determine the risk factors for age-related macular degeneration (AMD) in Algerians, and compare these data with those on North Africans living in Italy. METHODS: All patients over 55 years of age consulting one of the 23 involved Algerian ophthalmologists were invited to participate, and 1,183 patients were included. Data collection was standardized based on the Simplified Thea Risk Assessment Scale (STARS) questionnaire. A similar study was conducted in North Africans living in Italy (n = 1,011). Patients with only soft drusen and/or pigmentary abnormalities were classified as early AMD, and patients with geographic atrophy and/or neovascular AMD were classified as late AMD. RESULTS: In the final multivariate model, risk for early and/or late AMD was significantly increased with older age, family history of AMD, Black ethnicity, atherosclerosis, beer consumption, high fruit consumption, cataract surgery, myopia, and hyperopia. High consumption of green vegetables was associated with lower risk for both early and late AMD. In comparison with North Africans from Italy, Algerians generally had a healthier profile (younger, less obesity, smoking, and cardiovascular diseases, and higher consumption of fruits and vegetables) and a lower risk for AMD. CONCLUSION: This study documents risk factors for AMD in North-African populations for the first time. PMID- 27410058 TI - Are religion and spirituality barriers or facilitators to treatment for HIV: a systematic review of the literature. AB - Much attention has been given to the relationship between religion/spirituality (R/S) and HIV in recent years, but comparatively little has been explored in regard to R/S and HIV testing, retention in care, and adherence to medication. Religious views concerning HIV risk behavior pose challenges to communication and education about sexual health in religious communities and may serve as barriers to HIV treatment and care. Conversely, religious coping and spiritual well-being, as well as social support could serve as facilitators to HIV treatment and care. This study aims to fill a gap in the literature by addressing the following questions: (1) what dimensions of R/S have been found to be factors associated with HIV outcomes?; (2) which R/S factors function as barriers or facilitators to care among people living with HIV (PLWH)?; and (3) which R/S factors, if any, vary across socio-demographic groups? Thirty-three empirical articles were identified for systematic review. Of the 33 empirical studies included, 24 studies found that at least one measure of R/S was associated with better adherence and clinical health outcomes. Twelve studies found at least one measure of R/S to be associated with poorer adherence and clinical health outcomes. Seven of the studies found at least one R/S measure to have no significant association with outcomes. Though all of the studies included in this review focused on R/S experiences of PLWH, there was very little consistency in regard to measurement of R/S. Studies in this review included a wide range of R/S measures, including beliefs, religious/spiritual practices, R/S coping, organizational religion, and many more. Of the 33 studies reviewed, only 9 focused on unique populations such as women, people with histories of substance abuse, immigrants, etc. Findings from this review highlight opportunities for more studies in various populations using standardized R/S measures. PMID- 27410057 TI - Protection of human gammaB-crystallin from UV-induced damage by epigallocatechin gallate: spectroscopic and docking studies. AB - The transparency of the human eye lens depends on the solubility and stability of the structural proteins of the eye lens, the crystallins. Although the mechanism of cataract formation is still unclear, it is believed to involve protein misfolding and/or aggregation of proteins due to the influence of several external factors such as ultraviolet (UV) radiation, low pH, temperature and exposure to chemical agents. In this article, we report the study of UV induced photo-damage (under oxidative stress) of recombinant human gammaB-crystallin in vitro in the presence of the major green tea polyphenol, (-)-epigallocatechin gallate (EGCG). We have shown that EGCG has the ability to protect human gammaB crystallin from oxidative stress-induced photo-damage. PMID- 27410059 TI - Dual-wavelength fiber laser operating above 2 MUm based on cascaded single-mode multimode-single-mode fiber structures. AB - A stable dual-wavelength Tm3+:Ho3+ co-doped fiber laser operating above 2 MUm based on cascaded single-mode-multimode-single-mode (SMS) fiber structures is proposed and experimentally demonstrated. Based on the theoretical analysis of the transmission properties of the SMS fiber structure, two cascaded SMS fiber devices with different multimode fiber (MMF) lengths were used in our laser system, where one acted as a long-pass filter to suppress the competitive laser below 2 MUm, and the other worked as a band-pass filter to select the specific operating wavelengths of the laser. Dual-wavelength operation of the fiber laser at 2002.8 and 2016.1 nm has been achieved in the experiment with a signal to a noise ratio up to 50 dB. PMID- 27410060 TI - Measurement of high-birefringent spun fiber parameters using short-length fiber Bragg gratings. AB - Spectral polarization characteristics of short-length fiber Bragg gratings UV written in a highly-birefringent spun-fiber have been investigated. Based on the analysis of the characteristics the technique for measuring the built-in linear phase birefringence as well as the spin period in this fiber type has been suggested. In this method the birefringence dispersion is excluded and therefore the built-in linear phase birefringence can be measured with an improved accuracy. PMID- 27410061 TI - Intense THz Pulses with large ponderomotive potential generated from large aperture photoconductive antennas. AB - We report the generation of free space terahertz (THz) pulses with energy up to 8.3 +/- 0.2 uJ from an encapsulated interdigitated ZnSe Large Aperture Photo Conductive Antenna (LAPCA). An aperture of 12.2 cm2 is illuminated using a 400 nm pump laser with multi-mJ energies at 10 Hz repetition rate. The calculated THz peak electric field is 331 +/- 4 kV/cm with a spectrum characterized by a median frequency of 0.28 THz. Given its relatively low frequency, this THz field will accelerate charged particles efficiently having very large ponderomotive energy of 15 +/- 1 eV for electrons in vacuum. The scaling of the emission is studied with respect to the dimensions of the antenna, and it is observed that the capacitance of the LAPCA leads to a severe decrease in and distortion of the biasing voltage pulse, fundamentally limiting the maximum applied bias field and consequently the maximum energy of the radiated THz pulses. In order to demonstrate the advantages of this source in the strong field regime, an open-aperture Z-scan experiment was performed on n-doped InGaAs, which showed significant absorption bleaching. PMID- 27410062 TI - W-band photonic-wireless link with a Schottky diode envelope detector and bend insensitive fiber. AB - The performance and potential of a W-band radio-over-fiber link is analyzed, including a characterization of the wireless channel. The presented setup focuses on minimizing complexity in the radio frequency domain, using a passive radio frequency transmitter and a Schottky diode based envelope detector. Performance is experimentally validated with carriers at 75-87GHz over wireless distances of 30-70m. Finally the necessity for and impact of bend insensitive fiber for on site installation are discussed and experimentally investigated. PMID- 27410063 TI - Multi-frequency fringe projection profilometry based on wavelet transform. AB - Based on wavelet transforms (WTs), an alternative multi-frequency fringe projection profilometry is described. Fringe patterns with multiple frequencies are projected onto an object and the reflected patterns are recorded digitally. Phase information for every pattern is calculated by identifying the ridge that appears in WT results. Distinct from the phase unwrapping process, a peak searching algorithm is applied to obtain object height from the phases of the different frequency for a single point on the object. Thus, objects with large discontinuities can be profiled. In comparing methods, the height profiles obtained from the WTs have lower noise and higher measurement accuracy. Although measuring times are similar, the proposed method offers greater reliability. PMID- 27410064 TI - Refraction effects in soft x-ray multilayer blazed gratings. AB - A 2500 lines/mm Multilayer Blazed Grating (MBG) optimized for the soft x-ray wavelength range was fabricated and tested. The grating coated with a W/B4C multilayer demonstrated a record diffraction efficiency in the 2nd blazed diffraction order in the energy range from 500 to 1200 eV. Detailed investigation of the diffraction properties of the grating demonstrated that the diffraction efficiency of high groove density MBGs is not limited by the normal shadowing effects that limits grazing incidence x-ray grating performance. Refraction effects inherent in asymmetrical Bragg diffraction were experimentally confirmed for MBGs. The refraction affects the blazing properties of the MBGs and results in a shift of the resonance wavelength of the gratings and broadening or narrowing of the grating bandwidth depending on diffraction geometry. The true blaze angle of the MBGs is defined by both the real structure of the multilayer stack and by asymmetrical refraction effects. Refraction effects can be used as a powerful tool in providing highly efficient suppression of high order harmonics. PMID- 27410065 TI - Semi-automated infrared simulation on real urban scenes based on multi-view images. AB - The development of modern infrared applications require simulating thermal representations for targets of interest. However, generating geometric models for simulation has been a laborious, time-consuming work, which greatly limits the practical applications in real-world. In order to reduce the man-in-the-loop requirements, we devise a method that directly and semi-automatically simulates infrared signatures of real urban scenes. From raw meshes generated by multi-view stereo, we automatically produce a simplified watertight model through piecewise planar 3D reconstruction. Model surface is subdivided into quality mesh elements to attach material attributes. For each element, heat balance equation is solved so as to render the whole scene by synthesizing the radiance distribution in infrared waveband. The credibility and effectiveness of our method are confirmed by comparing simulation results to the measured data in real-world. Our experiments on various types of buildings and large scale scene show that the proposed pipeline simulates meaningful infrared scenes while being robust and scalable. PMID- 27410066 TI - Graded-index optical dimer formed by optical force. AB - We propose an optical dimer formed from two spherical lenses bound by the pressure that light exerts on matter. With the help of the method of force tracing, we find the required graded-index profiles of the lenses for the existence of the dimer. We study the dynamics of the opto-mechanical interaction of lenses under the illumination of collimated light beams and quantitatively validate the performance of proposed dimer. We also examine the stability of dimer due to the lateral misalignments and we show how restoring forces bring the dimer into lateral equilibrium. The dimer can be employed in various practical applications such as optical manipulation, sensing and imaging. PMID- 27410067 TI - High-performance InGaN-based green light-emitting diodes with quaternary InAlGaN/GaN superlattice electron blocking layer. AB - In this study, high-performance InGaN-based green light-emitting diodes (LEDs) with a quaternary InAlGaN/GaN superlattice electron blocking layer (QSL-EBL) have been demonstrated. The band structural simulation was employed to investigate the electrostatic field and carriers distribution, show that the efficiency and droop behavior can be intensively improved by using a QSL-EBL in LEDs. The QSL-EBL structure can reduce the polarization-related electrostatic fields in the multiple quantum wells (MQWs), leading to a smoother band diagram and a more uniform carriers distribution among the quantum wells under forward bias. In comparison with green LEDs with conventional bulk-EBL structure, the light output power of LEDs with QSL-EBL was greatly enhanced by 53%. The efficiency droop shows only 30% at 100 A/cm2 comparing to its peak value, suggesting that the QSL-EBL LED is promising for future white lighting with high performance. PMID- 27410068 TI - Sub-kilohertz laser linewidth narrowing using polarization spectroscopy. AB - We identify several beneficial characteristics of polarization spectroscopy as an absolute atomic reference for frequency stabilization of lasers, and demonstrate sub-kilohertz laser spectral linewidth narrowing using polarization spectroscopy with high-bandwidth feedback. Polarization spectroscopy provides a highly dispersive velocity-selective absolute atomic reference based on frequency dependent birefringence in an optically pumped atomic gas. The pumping process leads to dominance of the primary closed transition, suppressing closely-spaced subsidiary resonances which reduce the effective capture range for conventional atomic references. The locking signal is based on subtraction of two orthogonal polarization signals, reducing the effect of laser intensity noise to the shot noise limit. We measure noise-limited servo bandwidth comparable to that of a high-finesse optical cavity without the frequency limit or complexity imposed by optical modulation normally associated with high bandwidth laser frequency stabilization. We demonstrate narrowing to 600+/-100 Hz laser linewidth using the beatnote between two similarly locked external cavity diode lasers. PMID- 27410069 TI - Design of tunable GHz-frequency optomechanical crystal resonators. AB - We present a silicon optomechanical nanobeam design with a dynamically tunable acoustic mode at 10.2 GHz. The resonance frequency can be shifted by 90 kHz/V2 with an on-chip capacitor that was optimized to exert forces up to 1 uN at 10 V operation voltage. Optical resonance frequencies around 190 THz with Q-factors up to 2.2 * 106 place the structure in the well resolved sideband regime with vacuum optomechanical coupling rates up to g0/2pi = 353 kHz. Tuning can be used, for instance, to overcome variation in the device-to-device acoustic resonance frequency due to fabrication errors, paving the way for optomechanical circuits consisting of arrays of optomechanical cavities. PMID- 27410070 TI - Polarization beam splitters, converters and analyzers based on a metasurface composed of regularly arranged silicon nanospheres with controllable coupling strength. AB - A metasurface composed of regularly arranged silicon (Si) nanospheres (NSs) with coupling was investigated both theoretically and numerically based on the Mie theory, the simple Lorentz line shape model and the finite-difference time-domain technique. By deliberately controlling the coupling strength between Si NSs through the design of the lattice constants of a rectangular lattice, polarization beam splitters, converters and analyzers with good performance can be successfully constructed. A square lattice as well as a large incidence angle was employed to build the polarization beam splitters and converters. At an incidence angle of 80 degrees , the polarization beam splitters can completely reflect the s-polarized light and transmit the p-polarized light in a wavelength region of 510-620 nm. For a circularly polarized light incident on the polarization converters, one can get s-polarized light in the reflection direction and p-polarized light in the transmission direction. For the polarization beam analyzers, a rectangular lattice with deliberately chosen lattice constants was employed and the transmissivity of a linearly polarized light can be continuously adjusted from 0 to ~0.90 by simply rotating the metasurface. We revealed that the broadening of either the electric dipole resonance or the magnetic dipole resonance or both of them, which is induced by the asymmetric coupling of Si NSs, is responsible for the modification in the transmissivity spectrum of the metasurface. Our findings provide a guideline for designing photonic devices based on the metasurfaces composed of Si NSs with controllable coupling strength. PMID- 27410071 TI - Second harmonic generation in thin optical fibers via cladding modes. AB - Since silica goes under the category of amorphous materials, it is difficult to investigate important processes such as second harmonic generation (SHG) in silica-based fibers. In this paper, we proposed a method for SHG relaying on cladding modes as pump modes. Cladding modes are introduced in optical fibers through tilted long period grating (T-LPG), where power of core mode is transferred into cladding modes. By functionalizing T-LPG with nonlinear coating, the interaction occurs between cladding modes and the coating material, consequently second harmonic signal (SHS) is generated with efficiency up to 0.14%. PMID- 27410072 TI - Coupling to modes of a near-confocal optical resonator using a digital light modulator. AB - Digital micromirror devices (DMD) provide a robust platform with which to implement digital holography, in principle providing the means to rapidly generate propagating transverse electromagnetic fields with arbitrary mode profiles at visible and IR wavelengths. We use a DMD to probe a Fabry-Perot cavity in single-mode and near-degenerate confocal configurations. Pumping arbitrary modes of the cavity is possible with excellent specificity by virtue of the spatial overlap between the incident light field and the cavity mode. PMID- 27410073 TI - Optical micro-particle size detection by phase-generated carrier demodulation. AB - We demonstrate an optical micro-particle size detection technique based on phase sensing by a fiber interferometer through phase-generated carrier (PGC) modulation/demodulation. Particle diameters were resolved from phase shift due to particle-induced optical scattering. Polystyrene nanoparticles, air bubbles and yeast cells in a microfluidic channel were tested using this technique, and particle diameters ranging from 0.7 to 5.5 MUm can be resolved in real-time. In comparison with existing amplitude-sensing techniques which require tens of milliwatts of laser irradiance, phase-sensing through PGC can successfully utilize probe laser powers as low as 220 MUW to measure the test particle sizes. We further constructed a theoretical model based on phase scattering and PGC demodulation, which obtained good agreement between experimental data and calculated phase shift as a function of particle time-of-flight. This technique may be applied to a wide range of potential applications, ranging from real-time analysis of clinically relevant cell samples, to contamination control of processing fluids used in the semiconductor industry. PMID- 27410074 TI - Tunable multispectral plasmon induced transparency based on graphene metamaterials. AB - A dynamically wavelength tunable multispectral plasmon induced transparency (PIT) device based on graphene metamaterials, which is composed of periodically patterned graphene double layers separated by a dielectric layer, is proposed theoretically and numerically in the terahertz frequency range. Considering the near-field coupling of different graphene layers and the bright-dark mode coupling in the same graphene layer, the coupled Lorentz oscillator model is adapted to explain the physical mechanism of multispectral EIT-like responses. The simulated transmission based on the finite-difference time-domain (FDTD) solutions indicates that the shifting and depth of the EIT resonances in multiple PIT windows are controlled by different geometrical parameters and Fermi energies distributions. A design scheme with graphene integration is employed, which allows independent tuning of resonance frequencies by electrostatically changing the Fermi energies of graphene double layer. Active control of the multispectral EIT-like responses enables the proposed device to be widely applied in optical information processing as tunable sensors, switches, and filters. PMID- 27410075 TI - Simultaneous measurement of strain and temperature based on hybrid EDF/Brillouin laser. AB - Simultaneous temperature and strain sensing is experimentally demonstrated based on erbium-doped fiber laser (EDFL) and Brillouin erbium fiber laser (BEFL) incorporated in a single ring laser cavity. The EDFL can be switched to BEFL by injecting the Brillouin pump into the laser cavity. Longitudinal modes beat frequency and Brillouin frequency shift are monitored to discriminate strain and temperature. The longitudinal modes beat frequency is measured by observing the self-beating signals of the EDFL, while the Brillouin frequency shift is measured by monitoring the heterodyning signal of the BEFL. The simultaneous measurement errors of strain and temperature are within +/- 25.8MUepsilon and +/- 0.8 degrees C. The sensor is of simple structure and compact size. PMID- 27410076 TI - Augmented reality three-dimensional display with light field fusion. AB - A video see-through augmented reality three-dimensional display method is presented. The system that is used for dense viewpoint augmented reality presentation fuses the light fields of the real scene and the virtual model naturally. Inherently benefiting from the rich information of the light field, depth sense and occlusion can be handled under no priori depth information of the real scene. A series of processes are proposed to optimize the augmented reality performance. Experimental results show that the reconstructed fused 3D light field on the autostereoscopic display is well presented. The virtual model is naturally integrated into the real scene with a consistence between binocular parallax and monocular depth cues. PMID- 27410077 TI - Arbitrary shaping of on-axis amplitude of femtosecond Bessel beams with a single phase-only spatial light modulator. AB - Arbitrary shaping of the on-axis intensity of Bessel beams requires spatial modulation of both amplitude and phase. We develop a non-iterative direct space beam shaping method to generate Bessel beams with high energy throughput from direct space with a single phase-only spatial light modulator. For this purpose, we generalize the approach of Bolduc et al. to non-uniform input beams. We point out the physical limitations imposed on the on-axis intensity profile for unidirectional beams. Analytical, numerical and experimental results are provided. PMID- 27410078 TI - Microcavity with saturable nonlinearity under simultaneous resonant and nonresonant pumping: multistability, Hopf bifurcations and chaotic behaviour. AB - We studied optical response of microcavity non-equilibrium exciton-polariton Bose Einstein condensate with saturable nonlinearity under simultaneous resonant and non-resonant pumping. We demonstrated the emergence of multistabile behavior due to the saturation of the excitonic absorption. Stable periodic Rabi-type oscillations of the excitonic and photonic condensate components in the regime of the stationary pump and their transition to the chaotic dynamics through the cascade of Hopf bifurcations by tuning of the electrical pump are revealed. PMID- 27410079 TI - Three-dimensional-printed gas dynamic virtual nozzles for x-ray laser sample delivery. AB - Reliable sample delivery is essential to biological imaging using X-ray Free Electron Lasers (XFELs). Continuous injection using the Gas Dynamic Virtual Nozzle (GDVN) has proven valuable, particularly for time-resolved studies. However, many important aspects of GDVN functionality have yet to be thoroughly understood and/or refined due to fabrication limitations. We report the application of 2-photon polymerization as a form of high-resolution 3D printing to fabricate high-fidelity GDVNs with submicron resolution. This technique allows rapid prototyping of a wide range of different types of nozzles from standard CAD drawings and optimization of crucial dimensions for optimal performance. Three nozzles were tested with pure water to determine general nozzle performance and reproducibility, with nearly reproducible off-axis jetting being the result. X ray tomography and index matching were successfully used to evaluate the interior nozzle structures and identify the cause of off-axis jetting. Subsequent refinements to fabrication resulted in straight jetting. A performance test of printed nozzles at an XFEL provided high quality femtosecond diffraction patterns. PMID- 27410080 TI - Wireless OAM transmission system based on elliptical microstrip patch antenna. AB - The multiplexing transmission has always been a focus of attention for communication technology. In this paper, the radiation characteristics of circular microstrip patch antenna was firstly analyzed based on cavity model theory, and then spiral beams carrying orbital angular momentum (OAM) were generated, using elliptical microstrip patch antenna, with a single feed probe instead of a standard circular patch with two feedpoints. Moreover, by combining the proposed elliptic microstrip patch antenna with Universal Software Radio Peripheral (USRP), a wireless OAM transmission system was established and the real-time transmission of text, image and video in a real channel environment was realized. Since the wireless OAM transmission has the advantage of good safety and high spectrum utilization efficiency, this work has theoretical significance and potential application. PMID- 27410081 TI - Theoretical study on the Cerenkov-type second-harmonic generation in optical superlattices without paraxial approximation. AB - In this paper, the Cerenkov-type second-harmonic generation in bulk optical superlattices has been studied theoretically with the non-paraxial wave equations, where the paraxial approximation is avoided. The corresponding phase matching condition is determined strictly by solving the non-paraxial wave equations under proper boundary conditions, and the result coincides well with the traditional Cerenkov phase-matching condition. In addition, a backward Cerenkov phase-matching condition is deduced from the wave equations as well, and the physical requirement of this condition is clarified. PMID- 27410082 TI - Broadband linearization in photonic time-stretch analog-to-digital converters employing an asymmetrical dual-parallel Mach-Zehnder modulator and a balanced detector. AB - A broadband linearization scheme for time-stretch analog-to-digital converters (TS-ADCs) is proposed based on an asymmetrical dual-parallel Mach-Zehnder modulator and a balanced detector. The theoretical and simulation results indicate that, compared with the differential and arcsine operation method generally employed in TS-ADCs, the proposed scheme has a superior performance on enhancing the spur-free dynamic range and suppressing the even-order distortions and the third-order spurs even under a large modulation depth. Additionally, the proposed scheme realizes online linearization. Therefore, it has the potential to enhance the dynamic range of a broadband TS-ADC in real time. PMID- 27410083 TI - Scattering effects and high-spatial-frequency nanostructures on ultrafast laser irradiated surfaces of zirconium metallic alloys with nano-scaled topographies. AB - The origin of high-spatial-frequency laser-induced periodic surface structures (HSFL) driven by incident ultrafast laser fields, with their ability to achieve structure resolutions below lambda/2, is often obscured by the overlap with regular ripples patterns at quasi-wavelength periodicities. We experimentally demonstrate here employing defined surface topographies that these structures are intrinsically related to surface roughness in the nano-scale domain. Using Zr based bulk metallic glass (Zr-BMG) and its crystalline alloy (Zr-CA) counterpart formed by thermal annealing from its glassy precursor, we prepared surfaces showing either smooth appearances on thermoplastic BMG or high-density nano protuberances from randomly distributed embedded nano-crystallites with average sizes below 200 nm on the recrystallized alloy. Upon ultrashort pulse irradiation employing linearly polarized 50 fs, 800 nm laser pulses, the surfaces show a range of nanoscale organized features. The change of topology was then followed under multiple pulse irradiation at fluences around and below the single pulse threshold. While the former material (Zr-BMG) shows a specific high quality arrangement of standard ripples around the laser wavelength, the latter (Zr-CA) demonstrates strong predisposition to form high spatial frequency rippled structures (HSFL). We discuss electromagnetic scenarios assisting their formation based on near-field interaction between particles and field-enhancement leading to structure linear growth. Finite-difference-time-domain simulations outline individual and collective effects of nanoparticles on electromagnetic energy modulation and the feedback processes in the formation of HSFL structures with correlation to regular ripples (LSFL). PMID- 27410084 TI - Efficient, low threshold, cryogenic Ho:YAG laser. AB - We report the development of an efficient, liquid-nitrogen conduction cooled Ho:YAG slab laser with good beam quality. Detailed measurements resolving the structure of the 1900-1911 nm absorption band in Ho:YAG at 77 K are presented. Stress-free conduction cooled mounting of the Ho:YAG slab was demonstrated and the resulting laser operated with a large mode volume of 42 mm3, a slope efficiency of 75% and a threshold of 0.84 W. To our knowledge this corresponds to the lowest reported threshold intensity for a Ho:YAG laser. PMID- 27410085 TI - Effects of LiDAR point density, sampling size and height threshold on estimation accuracy of crop biophysical parameters. AB - Vegetation leaf area index (LAI), height, and aboveground biomass are key biophysical parameters. Corn is an important and globally distributed crop, and reliable estimations of these parameters are essential for corn yield forecasting, health monitoring and ecosystem modeling. Light Detection and Ranging (LiDAR) is considered an effective technology for estimating vegetation biophysical parameters. However, the estimation accuracies of these parameters are affected by multiple factors. In this study, we first estimated corn LAI, height and biomass (R2 = 0.80, 0.874 and 0.838, respectively) using the original LiDAR data (7.32 points/m2), and the results showed that LiDAR data could accurately estimate these biophysical parameters. Second, comprehensive research was conducted on the effects of LiDAR point density, sampling size and height threshold on the estimation accuracy of LAI, height and biomass. Our findings indicated that LiDAR point density had an important effect on the estimation accuracy for vegetation biophysical parameters, however, high point density did not always produce highly accurate estimates, and reduced point density could deliver reasonable estimation results. Furthermore, the results showed that sampling size and height threshold were additional key factors that affect the estimation accuracy of biophysical parameters. Therefore, the optimal sampling size and the height threshold should be determined to improve the estimation accuracy of biophysical parameters. Our results also implied that a higher LiDAR point density, larger sampling size and height threshold were required to obtain accurate corn LAI estimation when compared with height and biomass estimations. In general, our results provide valuable guidance for LiDAR data acquisition and estimation of vegetation biophysical parameters using LiDAR data. PMID- 27410086 TI - Temperature dependent carrier localization in AlGaInN near-ultraviolet light emitting diodes. AB - We investigate the carrier localization effect in the low-indium ultraviolet AlGaInN light-emitting diodes with a 365 nm peak and a wide yellow luminous band over the visible range. Temperature-dependent electroluminescence spectra (EL) are measured under a wide range of temperature. We found that carrier localization effect relies on the carrier mobility and manifests itself by altering several macroscopic quantities, such as ELs and electrical resistance of the device. Under moderate injection densities, plots of EL peak energy vs. temperatures exhibits S-shapes. At low temperatures, line-width broadening in EL spectra and irregular humps in I-V curves were observed at similar level of injection densities. Both phenomena diminish as temperature increases and eventually disappear at room temperature. All the results stem from carrier localization and following delocalization effect. It suggests that the carrier mobility determine the degree of carrier localization effect - inactive carriers tend to be localized at low temperature but escape at high temperature from bindings of localization centers. As a result, carrier localization is intense only at low temperature for low-indium devices. PMID- 27410087 TI - InGaN light emitting diodes with a nanopipe layer formed from the GaN epitaxial layer. AB - A Si-heavy doped GaN:Si epitaxial layer is transformed into a directional nanopipe GaN layer through a laser-scribing process and a selectively electrochemical (EC) etching process. InGaN light-emitting diodes (LEDs) with an EC-treated nanopipe GaN layer have a high light extraction efficiency. The direction of the nanopipe structure was directed perpendicular to the laser scribing line and was guided by an external bias electric field. An InGaN LED structure with an embedded nanopipe GaN layer can enhance external quantum efficiency through a one-step epitaxial growth process and a selective EC etching process. A birefringence optical property and a low effective refractive index were observed in the directional-nanopipe GaN layer. PMID- 27410088 TI - Fabrication of a phase photon sieve on an optical fiber tip by focused ion beam nanomachining for improved fiber to silicon photonics waveguide light coupling. AB - We report the fabrication of a phase photon sieve (PS) on the tip of a standard single mode fiber by focused ion beam (FIB) milling. The fiber tip was dip-coated with a conductive polymer ( PEDOT: PSS) as an alternative, more advantageous method to the metallization prior to FIB milling. The near field scans of the intensity profile along the optical axis under fiber illumination of a laser at lambda = 1.55 MUm are presented. We have analyzed the focusing properties and demonstrated the validity of our structure for light coupling into silicon photonics waveguides with improved efficiency and alignment tolerance. PMID- 27410089 TI - Second-order statistics of a radially polarized cosine-Gaussian correlated Schell model beam in anisotropic turbulence. AB - Recently, we introduced a new class of radially polarized cosine-Gaussian correlated Schell-model (CGCSM) beams of rectangular symmetry based on the partially coherent electromagnetic theory [Opt. Express23, 33099 (2015)]. In this paper, we extend the work to study the second-order statistics such as the average intensity, the spectral degree of coherence, the spectral degree of polarization and the state of polarization in anisotropic turbulence based on an extended von Karman power spectrum with a non-Kolmogorov power law alpha and an effective anisotropic parameter. Analytical formulas for the cross-spectral density matrix elements of a radially polarized CGCSM beam in anisotropic turbulence are derived. It is found that the second-order statistics are greatly affected by the source correlation function, and the change in the turbulent statistics induces relatively small effect. The significant effect of anisotropic turbulence on the beam parameters mainly appears nearalpha=3.1, and decreases with the increase of the anisotropic parameter. Furthermore, the polarization state exhibits self-splitting property and each beamlet evolves into a radially polarized structure in the far field. Our work enriches the classical coherence theory and may be important for free-space optical communications. PMID- 27410090 TI - Optimizing visual comfort for stereoscopic 3D display based on color-plus-depth signals. AB - Visual comfort is a long-facing problem in stereoscopic 3D (S3D) display. In this paper, targeting to produce S3D content based on color-plus-depth signals, a general framework for depth mapping to optimize visual comfort for S3D display is proposed. The main motivation of this work is to remap the depth range of color plus-depth signals to a new depth range that is suitable to comfortable S3D display. Towards this end, we first remap the depth range globally based on the adjusted zero disparity plane, and then present a two-stage global and local depth optimization solution to solve the visual comfort problem. The remapped depth map is used to generate the S3D output. We demonstrate the power of our approach on perceptually uncomfortable and comfortable stereoscopic images. PMID- 27410091 TI - Raman scattering and red fluorescence in the photochemical transformation of dry tryptophan particles. AB - Tryptophan is a fluorescent amino acid common in proteins. Its absorption is largest for wavelengths lambda ? 290 nm and its fluorescence emissions peak around 300-350 nm, depending upon the local environment. Here we report the observation of red fluorescence near 600 nm emerging from 488-nm continuous-wave (CW) laser photoexcitation of dry tryptophan (Trp) particles. With an excitation intensity below 0.5 kW/cm2, dry Trp particles yield distinctive Raman scattering peaks in the presence of relatively weak and spectrally broad emissions with lambda ~500-700 nm, allowing estimation of particle temperature at low excitation intensities. When the photoexcitation intensity is increased to 1 kW/cm2 or more for a few minutes, fluorescence intensity dramatically increases by more than two orders of magnitude. The fluorescence continues to increase in intensity and gradually shift to the red when photoexcitation intensity and the duration of exposure are increased. The resulting products absorb at visible wavelengths and generate red fluorescence with lambda ~ 650-800 nm with 633-nm CW laser excitation. We attribute the emergence of orange and red fluorescence in the Trp products to a photochemical transformation that is instigated by weak optical transitions to triplet states in Trp with 488-nm excitation and which may be expedited by a photothermal effect. PMID- 27410092 TI - Crosstalk analysis of ring resonator switches for all-optical routing. AB - Optical switches based on ring resonator cavities were fabricated by a silicon photonics foundry process and analyzed for optical crosstalk at various data rates and channel spacings. These devices were compared to commercial bandpass filters and at 20Gb/s, 0.5dB power penalty is observed due to spectral filtering for bit error ratio threshold of 1 * 10-9. Concurrent modulation at 20Gb/s with a channel spacing as narrow as 40GHz shows error-free transmission with 1dB power penalty as compared to wider channel spacing for the ring-based switch. PMID- 27410093 TI - Wide bandwidth and high resolution planar filter array based on DBR-metasurface DBR structures. AB - We propose and experimentally demonstrate a planar array of optical bandpass filters composed of low loss dielectric metasurface layers sandwiched between two distributed Bragg reflectors (DBRs). The two DBRs form a Fabry-Perot resonator whose center wavelength is controlled by the design of the transmissive metasurface layer which functions as a phase shifting element. We demonstrate an array of bandpass filters with spatially varying center wavelengths covering a wide range of operation wavelengths of 250nm around lambda = 1550nm (Deltalambda/lambda = 16%). The center wavelengths of each filter are independently controlled only by changing the in-plane geometry of the sandwiched metasurfaces, and the experimentally measured quality factors are larger than 700. The demonstrated filter array can be directly integrated on top of photodetector arrays to realize on-chip high-resolution spectrometers with free space coupling. PMID- 27410094 TI - Quantitative phase imaging of weakly scattering objects using partially coherent illumination. AB - In this paper, we extend our recent work on partially coherent quantitative phase imaging (pcQPI) from two-dimensional (2D) to three-dimensional (3D) imaging of weakly scattering samples. Due to the mathematical complexity, most theoretical modeling of quantitative phase image formation under partial coherence has focused on thin, well-focused samples. It is unclear how these abberations are affected by defocusing. Also, as 3D QPI techniques continue to develop, a better model needs to be developed to understand and quantify these aberrations when imaging thicker samples. Here, using the first order Born's approximation, we derived a mathematical framework that provides an intuitive model of image formation under varying degrees of coherence. Our description provides a clear connection between the halo effect and phase underestimation, defocusing and the 3D structure of the sample under investigation. Our results agree very well with the experiments and show that the microscope objective defines the sectioning ability of the imaging system while the condenser lens is responsible for the halo effect. PMID- 27410095 TI - Integrated optical frequency shifter in silicon-organic hybrid (SOH) technology. AB - We demonstrate for the first time a waveguide-based frequency shifter on the silicon photonic platform using single-sideband modulation. The device is based on silicon-organic hybrid (SOH) electro-optic modulators, which combine conventional silicon-on-insulator waveguides with highly efficient electro-optic cladding materials. Using small-signal modulation, we demonstrate frequency shifts of up to 10 GHz. We further show large-signal modulation with optimized waveforms, enabling a conversion efficiency of -5.8 dB while suppressing spurious side-modes by more than 23 dB. In contrast to conventional acousto-optic frequency shifters, our devices lend themselves to large-scale integration on silicon substrates, while enabling frequency shifts that are several orders of magnitude larger than those demonstrated with all-silicon serrodyne devices. PMID- 27410096 TI - Electrically tunable Fano-type resonance of an asymmetric metal wire pair. AB - We theoretically and experimentally investigate the electrically tunable Fano type resonance of asymmetric metal wire pair loaded with varactor diodes. It is illustrated that Fano-type transmission spectrum with high quality factor Q appears as a result of interference between the dipole and quadrupole modes. The ohmic loss of series resistance in varactor diode makes major contribution to absorption. At the Fano-type resonance frequency, both the two metal wires exhibit the strongest electric resonance simultaneously, and the Fano-type resonance manifests a large group delay. As the bias voltage ranges from 0 V to 8 V, the Fano-type resonance frequency exhibits a prominent blueshift of 0.16 GHz and the transmission experiences a modulation with a modulation depth of 97%. PMID- 27410097 TI - Characterization of LDPC-coded orbital angular momentum modes transmission and multiplexing over a 50-km fiber. AB - Mode-division multiplexing over fibers has attracted increasing attention over the last few years as a potential solution to further increase fiber transmission capacity. In this paper, we demonstrate the viability of orbital angular momentum (OAM) modes transmission over a 50-km few-mode fiber (FMF). By analyzing mode properties of eigen modes in an FMF, we study the inner mode group differential modal delay (DMD) in FMF, which may influence the transmission capacity in long distance OAM modes transmission and multiplexing. To mitigate the impact of large inner mode group DMD in long-distance fiber-based OAM modes transmission, we use low-density parity-check (LDPC) codes to increase the system reliability. By evaluating the performance of LDPC-coded single OAM mode transmission over 50-km fiber, significant coding gains of >4 dB, 8 dB and 14 dB are demonstrated for 1 Gbaud, 2-Gbaud and 5-Gbaud quadrature phase-shift keying (QPSK) signals, respectively. Furthermore, in order to verify and compare the influence of DMD in long-distance fiber transmission, single OAM mode transmission over 10-km FMF is also demonstrated in the experiment. Finally, we experimentally demonstrate OAM multiplexing and transmission over a 50-km FMF using LDPC-coded 1-Gbaud QPSK signals to compensate the influence of mode crosstalk and DMD in the 50 km FMF. PMID- 27410098 TI - Determination of volume scattering parameters that reproduce the luminance characteristics of diffusers. AB - The extension of a well-known inverse technique, inverse adding-doubling (IAD), is investigated for determining the volume scattering properties of diffusers for display and lighting applications. The luminance characteristics of volume scattering diffusers are vital for these applications. Through a simulation study, it is shown that fitting solely to the scattered (angular) intensity information with the extended IAD method, results in a volume scattering characterization that also reproduces the correct (spatial and angular) luminance characteristics for a wide range of samples. The gap between the simulation work and the experimental application of the investigated fitting procedure is bridged by considering the effect of experimental error in the scattered intensity distributions. This does not significantly alter the presented conclusions. PMID- 27410099 TI - Reconfigurable photonic temporal differentiator based on a dual-drive Mach Zehnder modulator. AB - We propose and demonstrate a reconfigurable photonic temporal differentiator based on a dual drive Mach-Zehnder modulator (DDMZM). The differentiator can be reconfigured to different differentiation types by simply adjusting the bias voltage of DDMZM. Both simulations and experiments are carried out to verify the proposed scheme. In the experiment, a pair of polarity-reversed field differentiation and a pair of polarity-reversed intensity differentiation are successfully generated. The differentiation accuracy and conversion efficiency versus the time delay are also investigated. PMID- 27410100 TI - Polarization insensitive all-optical wavelength conversion of polarization multiplexed signals using co-polarized pumps. AB - We study and experimentally validate the vector theory of four-wave mixing (FWM) in semiconductor optical amplifiers (SOA). We use the vector theory of FWM to design a polarization insensitive all-optical wavelength converter, suitable for advanced modulation formats, using non-degenerate FWM in SOAs and parallelly polarized pumps. We demonstrate the wavelength conversion of polarization multiplexed (PM)-QPSK, PM-16QAM and a Nyquist WDM super-channel modulated with PM QPSK signals at a baud rate of 12.5 GBaud, with total data rates of 50 Gbps, 100 Gbps and 200 Gbps respectively. PMID- 27410101 TI - Fluid flow vorticity measurement using laser beams with orbital angular momentum. AB - Vorticity is one of the most important dynamic flow variables and is fundamental to the basic flow physics of many areas of fluid dynamics, including aerodynamics, turbulent flows and chaotic motion. We report on the direct measurements of fluid flow vorticity using a beam with orbital angular momentum that takes advantage of the rotational Doppler shift from microparticles intersecting the beam focus. Experiments are carried out on fluid flows with well characterized vorticity and the experimental results are found to be in excellent agreement with the expected values. This method allows for localized real-time determination of vorticity in a fluid flow with three-dimensional resolution. PMID- 27410102 TI - Two mirror X-ray pulse split and delay instrument for femtosecond time resolved investigations at the LCLS free electron laser facility. AB - We built a two-mirror based X-ray split and delay (XRSD) device for soft X-rays at the Linac Coherent Light Source free electron laser facility. The instrument is based on an edge-polished mirror design covering an energy range of 250 eV 1800 eV and producing a delay between the two split pulses variable up to 400 femtoseconds with a sub-100 attosecond resolution. We present experimental and simulation results regarding molecular dissociation dynamics in CH3I and CO probed by the XRSD device. We observed ion kinetic energy and branching ratio dependence on the delay times which were reliably produced by the XRSD instrument. PMID- 27410103 TI - Ultrafast, solid-state oscillators based on broadband, multisite Yb-doped crystals. AB - A detailed performance comparison of new interesting Yb-doped crystals in the same oscillator setup, with single-mode fiber-coupled diode laser pump is reported. We intended to assess the shortest pulses achievable with available SESAM technology, running a fair comparison with laser crystals Yb:KLuW, Yb:SSO, Yb:CALGO, Yb:CALYO and Yb:CaF2, very likely including the most promising choices for the next generation of commercial bulk ultrafast solid state systems. PMID- 27410104 TI - Modelling and measurement of the absolute level of power radiated by antenna integrated THz UTC photodiodes. AB - We determine the output impedance of uni-travelling carrier (UTC) photodiodes at frequencies up to 400 GHz by performing, for the first time, 3D full-wave modelling of detailed UTC photodiode structures. In addition, we demonstrate the importance of the UTC impedance evaluation, by using it in the prediction of the absolute power radiated by an antenna integrated UTC, over a broad frequency range and confirming the predictions by experimental measurements up to 185 GHz. This is done by means of 3D full-wave modelling and is only possible since the source (UTC) to antenna impedance match is properly taken into account. We also show that, when the UTC-to-antenna coupling efficiency is modelled using the classical junction-capacitance/series-resistance concept, calculated and measured levels of absolute radiated power are in substantial disagreement, and the maximum radiated power is overestimated by a factor of almost 7 dB. The ability to calculate the absolute emitted power correctly enables the radiated power to be maximised through optimisation of the UTC-to-antenna impedance match. PMID- 27410105 TI - Dynamic lens and monovision 3D displays to improve viewer comfort. AB - Stereoscopic 3D (S3D) displays provide an additional sense of depth compared to non-stereoscopic displays by sending slightly different images to the two eyes. But conventional S3D displays do not reproduce all natural depth cues. In particular, focus cues are incorrect causing mismatches between accommodation and vergence: The eyes must accommodate to the display screen to create sharp retinal images even when binocular disparity drives the eyes to converge to other distances. This mismatch causes visual discomfort and reduces visual performance. We propose and assess two new techniques that are designed to reduce the vergence accommodation conflict and thereby decrease discomfort and increase visual performance. These techniques are much simpler to implement than previous conflict-reducing techniques. The first proposed technique uses variable-focus lenses between the display and the viewer's eyes. The power of the lenses is yoked to the expected vergence distance thereby reducing the mismatch between vergence and accommodation. The second proposed technique uses a fixed lens in front of one eye and relies on the binocularly fused percept being determined by one eye and then the other, depending on simulated distance. We conducted performance tests and discomfort assessments with both techniques and compared the results to those of a conventional S3D display. The first proposed technique, but not the second, yielded clear improvements in performance and reductions in discomfort. This dynamic-lens technique therefore offers an easily implemented technique for reducing the vergence-accommodation conflict and thereby improving viewer experience. PMID- 27410106 TI - Laser system for identification, tracking, and control of flying insects. AB - Flying insects are common vectors for transmission of pathogens and inflict significant harm to humans and agricultural production in many parts of the world. We present proof of principle for an optical system capable of highly specific vector control. This system utilizes a combination of optical sources, detectors, and sophisticated software to search, detect, and identify flying insects in real-time, with the capability of eradication using a lethal laser pulse. We present data on two insect species to show species distinction; Diaphorina citri, a vector of the causal agent of citrus greening disease, and Anopheles stephensi, a malaria vector. PMID- 27410107 TI - Video-rate processing in tomographic phase microscopy of biological cells using CUDA. AB - We suggest a new implementation for rapid reconstruction of three-dimensional (3 D) refractive index (RI) maps of biological cells acquired by tomographic phase microscopy (TPM). The TPM computational reconstruction process is extremely time consuming, making the analysis of large data sets unreasonably slow and the real time 3-D visualization of the results impossible. Our implementation uses new phase extraction, phase unwrapping and Fourier slice algorithms, suitable for efficient CPU or GPU implementations. The experimental setup includes an external off-axis interferometric module connected to an inverted microscope illuminated coherently. We used single cell rotation by micro-manipulation to obtain interferometric projections from 73 viewing angles over a 180 degrees angular range. Our parallel algorithms were implemented using Nvidia's CUDA C platform, running on Nvidia's Tesla K20c GPU. This implementation yields, for the first time to our knowledge, a 3-D reconstruction rate higher than video rate of 25 frames per second for 256 * 256-pixel interferograms with 73 different projection angles (64 * 64 * 64 output). This allows us to calculate additional cellular parameters, while still processing faster than video rate. This technique is expected to find uses for real-time 3-D cell visualization and processing, while yielding fast feedback for medical diagnosis and cell sorting. PMID- 27410108 TI - Novel Ge waveguide platform on Ge-on-insulator wafer for mid-infrared photonic integrated circuits. AB - We present Ge rib waveguide devices fabricated on a Ge-on-insulator (GeOI) wafer as a proof-of-concept Ge mid-infrared photonics platform. Numerical analysis revealed that the driving current for a given optical attenuation in a carrier injection Ge waveguide device at a 1.95 MUm wavelength can be approximately five times smaller than that in a Si device, enabling in-line carrier-injection Ge optical modulators based on free-carrier absorption. We prepared a GeOI wafer with a 2-MUm-thick buried oxide layer (BOX) by wafer bonding. By using the GeOI wafer, we fabricated Ge rib waveguides. The Ge rib waveguides were transparent to 2 MUm wavelengths and the propagation loss was found to be 1.4 dB/mm, which may have been caused by sidewall scattering. We achieved a negligible bend loss in the Ge rib waveguide, even with a 5 MUm bend radius, owing to the strong optical confinement in the GeOI structure. We also formed a lateral p-i-n junction along the Ge rib waveguide to explore the capability of absorption modulation by carrier injection. By injecting current through the lateral p-i-n junction, we achieved optical intensity modulation in the 2 MUm band based on the free-carrier absorption in Ge. PMID- 27410109 TI - Measuring absolute frequencies beyond the GPS limit via long-haul optical frequency dissemination. AB - Global Positioning System (GPS) dissemination of frequency standards is ubiquitous at present, providing the most widespread time and frequency reference for the majority of industrial and research applications worldwide. On the other hand, the ultimate limits of the GPS presently curb further advances in high precision, scientific and industrial applications relying on this dissemination scheme. Here, we demonstrate that these limits can be reliably overcome even in laboratories without a local atomic clock by replacing the GPS with a 642-km-long optical fiber link to a remote primary caesium frequency standard. Through this configuration we stably address the 1S0 3P0 clock transition in an ultracold gas of 173Yb, with a precision that exceeds the possibilities of a GPS-based measurement, dismissing the need for a local clock infrastructure to perform beyond-GPS high-precision tasks. We also report an improvement of two orders of magnitude in the accuracy on the transition frequency reported in literature. PMID- 27410110 TI - Memory-based pulse amplitude modulation for short-reach fiber communications with intensity modulation and direct detection. AB - The low cost of an intensity modulation and direct detection system has made it an attractive choice for short-reach fiber communications. A longer fiber transmission length can be supported with the help of a combination of high-ary pulse amplitude modulation (PAM) and maximum likelihood sequence estimation (MLSE). For a further improvement on the system performance under a fiber dispersive channel, this paper proposes to add memory into PAM for spectrum compression. The memory-based PAM can be implemented with a simple pre-coding at the transmitter side while no extra requirement is necessary on the receiver side. Both theoretical and simulation results show that the memory-based PAM has a smaller mainlobe bandwidth and thus has a higher tolerance to the accumulated fiber dispersion. Compared with conventional memory-less PAM-4, the memory-based PAM-4 can effectively extend the maximum achievable fiber transmission length from 60km to 70km with the same number of MLSE states at the receiver. Moreover, this paper also proposes an optimization on the memory-based PAM and a further extension on the allowed fiber transmission length is achieved. PMID- 27410111 TI - Employing low-temperature barriers to achieve strain-relaxed and high-performance GaN-based LEDs. AB - The epitaxial structure design of low-temperature barriers has been adopted to promote strain relaxation in multiple quantum well (MQWs) and achieve high efficient GaN-based light-emitting diodes (LEDs). With these barriers, the relaxation value of wells increases from 0 to 4.59%. The strain-relaxed mechanism of low-temperature barriers is also discussed. The LED chip with the barriers grown at the TMIn flow of 75 sccm and the growth temperature of 830 degrees C has an optimal strain relaxation value of 1.53% in wells, and exhibits the largest light output power of 63.83 mW at the injection current of 65 mA, which is higher than that of conventional LED (51.89 mW) by 23%. In-depth studies reveal that the optimal low-temperature barriers remarkably promote the strain relaxation in wells without forming large density of crystalline defects. This achievement of high-efficiency LEDs sheds light on the future solid-state lighting applications. PMID- 27410112 TI - Towards refractive index sensitivity of long-period gratings at level of tens of um per refractive index unit: fiber cladding etching and nano-coating deposition. AB - In this work we report experimental results on optimizing the refractive index (RI) sensitivity of long-period gratings (LPGs) by fiber cladding etching and thin aluminum oxide (Al2O3) overlay deposition. The presented LPG takes advantage of work in the dispersion turning point (DTP) regime as well as the mode transition (MT) effect for higher-order cladding modes (LP09 and LP010). The MT was obtained by depositing Al2O3 overlays with single-nanometer precision using the Atomic Layer Deposition method (ALD). Etching of both the overlay and the fiber cladding was performed using hydrofluoric acid (HF). For shallow etching of the cladding, i.e., DTP observed at next = 1.429 and 1.439 RIU for an LPG with no overlay, followed by deposition of an overlay of up to 167 nm in thickness, HF etching allowed for post-deposition fine-tuning of the overlay thickness resulting in a significant increase in RI sensitivity mainly at the DTP of the LP09 cladding mode. However, at an external RI (next) above 1.39 RIU, the DTP of LP010 was noticed, and its RI sensitivity exceeded 9,000 nm/RIU. Deeper etching of the cladding, i.e., DTP observed for next above 1.45 RIU, followed by the deposition of thicker overlays (up to 201 nm in thickness) allowed the sensitivity to reach values of over 40,000 nm/RIU in a narrow RI range. Sensitivity exceeding 20,000 nm/RIU was obtained in an RI range suitable for label-free biosensing applications. PMID- 27410113 TI - Wavelet prism decomposition analysis applied to CARS spectroscopy: a tool for accurate and quantitative extraction of resonant vibrational responses. AB - We propose an approach, based on wavelet prism decomposition analysis, for correcting experimental artefacts in a coherent anti-Stokes Raman scattering (CARS) spectrum. This method allows estimating and eliminating a slowly varying modulation error function in the measured normalized CARS spectrum and yields a corrected CARS line-shape. The main advantage of the approach is that the spectral phase and amplitude corrections are avoided in the retrieved Raman line shape spectrum, thus significantly simplifying the quantitative reconstruction of the sample's Raman response from a normalized CARS spectrum in the presence of experimental artefacts. Moreover, the approach obviates the need for assumptions about the modulation error distribution and the chemical composition of the specimens under study. The method is quantitatively validated on normalized CARS spectra recorded for equimolar aqueous solutions of D-fructose, D-glucose, and their disaccharide combination sucrose. PMID- 27410114 TI - Multiple defocused coherent diffraction imaging: method for simultaneously reconstructing objects and probe using X-ray free-electron lasers. AB - The sample size must be less than the diffraction-limited focal spot size of the incident beam in single-shot coherent X-ray diffraction imaging (CXDI) based on a diffract-before-destruction scheme using X-ray free electron lasers (XFELs). This is currently a major limitation preventing its wider applications. We here propose multiple defocused CXDI, in which isolated objects are sequentially illuminated with a divergent beam larger than the objects and the coherent diffraction pattern of each object is recorded. This method can simultaneously reconstruct both objects and a probe from the coherent X-ray diffraction patterns without any a priori knowledge. We performed a computer simulation of the prposed method and then successfully demonstrated it in a proof-of-principle experiment at SPring-8. The prposed method allows us to not only observe broad samples but also characterize focused XFEL beams. PMID- 27410115 TI - OFDM and PAM comparison using a high baudrate low resolution IM/DD interface for 400G Ethernet access. AB - We compare OFDM and PAM for 400G Ethernet based on a 3-bit high baudrate IM/DD interface at 1550nm. We demonstrate 27Gb/s and 32Gb/s transmission over 10km SSMF using OFDM and PAM respectively. We show that capacity can be improved through adaptation/equalization to achieve 42Gb/s and 64Gb/s for OFDM and PAM respectively. Experimental results are used to create realistic simulations to extrapolate the performance of both modulation formats under varied conditions. For the considered interface we found that PAM has the best performance, OFDM is impaired by quantization noise. When the resolution limitation is relaxed, OFDM shows better performance. PMID- 27410116 TI - Augmenting the spectral efficiency of enhanced PAM-DMT-based optical wireless communications. AB - The energy efficiency of pulse-amplitude-modulated discrete multitone modulation (PAM-DMT) decreases as the modulation order of M-PAM modulation increases. Enhanced PAM-DMT (ePAM-DMT) was proposed as a solution to the reduced energy efficiency of PAM-DMT. This was achieved by allowing multiple streams of PAM-DMT to be superimposed and successively demodulated at the receiver side. In order to maintain a distortion-free unipolar ePAM-DMT system, the multiple time-domain PAM DMT streams are required to be aligned. However, aligning the antisymmetry in ePAM-DMT is complex and results in efficiency losses. In this paper, a novel simplified method to apply the superposition modulation on M-PAM modulated discrete multitone (DMT) is introduced. Contrary to ePAM-DMT, the signal generation of the proposed system, termed augmented spectral efficiency discrete multitone (ASE-DMT), occurs in the frequency domain. This results in an improved spectral and energy efficiency. The analytical bit error rate (BER) performance bound of the proposed system is derived and compared with Monte-Carlo simulations. The system performance is shown to offer significant electrical and optical energy savings compared with ePAM-DMT and DC-biased optical orthogonal frequency division multiplexing (DCO-OFDM). PMID- 27410117 TI - Performance of laser inter-satellite links with dynamic beam waist adjustment. AB - In this paper, we propose the idea of dynamic beam waist adjustment for laser inter-satellite communications, and study the performance of this dynamic-beam scheme. The beam waist adjustment is based on continuous detection of the instantaneous pointing error angle, which is performed at the transmitter side. Using a square to approximate the circular detector region, we obtain a closed form expression for calculating the proportion of power that can be collected by the receiver aperture, and derive a simple algebraic solution for the optimum dynamic beam waist. Due to its simple form, the dynamic beam waist value can be computed in real time at the transmitter, and therefore, the adjustment is practically implementable. It is shown that the performance of laser inter satellite links with dynamic beam waist is better than that with fixed beam waist. PMID- 27410118 TI - Quasi first-order Hermite Gaussian beam for enhanced sensitivity in Sagnac interferometer photothermal deflection spectroscopy. AB - The detection sensitivity of a Sagnac interferometer photothermal deflection spectroscopy was enhanced by changing the probe beam pattern from zero-order to a quasi-first-order Hermite Gaussian (QHG) beam. The nature of the higher order HG mode, where the beam pattern is preserved during propagation with an increased field gradient, is utilized to enhance the measurement sensitivity. In this spectroscopy, the lateral beam deflection due to the photothermal effect is sensitively detected as a change in the interference light intensity. The change in intensity is amplified due to the higher field gradient of the QHG(1,0) beam at the photodetector. This amplification effect was both numerically and experimentally demonstrated to obtain twofold improvement in the signal-to-noise ratio. PMID- 27410119 TI - Imaging through strong turbulence with a light field approach. AB - Under strong turbulence conditions, object's images can be severely distorted and become unrecognizable throughout the observing time. Conventional image restoring algorithms do not perform effectively in these circumstances due to the loss of good references on the object. We propose the use a plenoptic sensor as a light field camera to map a conventional camera image onto a cell image array in the image's sub-angular spaces. Accordingly, each cell image on the plenoptic sensor is equivalent to the image acquired by a sub-aperture of the imaging lens. The wavefront distortion over the lens aperture can be analyzed by comparing cell images in the plenoptic sensor. By using a modified "Laplacian" metric, we can identify a good cell image in a plenoptic image sequence. The good cell image corresponds with the time and sub-aperture area on the imaging lens where wavefront distortion becomes relatively and momentarily "flat". As a result, it will reveal the fundamental truths of the object that would be severely distorted on normal cameras. In this paper, we will introduce the underlying physics principles and mechanisms of our approach and experimentally demonstrate its effectiveness under strong turbulence conditions. In application, our approach can be used to provide a good reference for conventional image restoring approaches under strong turbulence conditions. This approach can also be used as an independent device to perform object recognition tasks through severe turbulence distortions. PMID- 27410120 TI - Germanium-on-SOI waveguides for mid-infrared wavelengths. AB - We report on the development of Germanium-on-SOI waveguides for mid-infrared wavelengths. The strip waveguides have been formed in 0.85 and 2 MUm thick Ge grown on SOI substrate with 220 nm thick Si overlayer. The propagation loss for various waveguide widths has been measured using the Fabry-Perot method with temperature tuning. The minimum loss of ~8 dB/cm has been achieved for 0.85 MUm thick Ge core using 3.682 MUm laser excitation. The transparency of these waveguides has been measured up to at least 3.82 MUm. PMID- 27410121 TI - Curvature effects on flexible surface plasmon resonance biosensing: segmented wave analysis. AB - We investigate the effect of surface curvature on characteristics of flexible surface plasmon resonance biosensors. For simplified analysis, segmentation-based approximation of curved substrates has been conducted in a range of curvature radius |r| > 225 MUm in the parallel and perpendicular light incidence with respect to the surface. The results suggest that resonance characteristics in general broaden with increased curvature due to larger momentum dispersion, the effect of which appears more prominent and direct in the parallel light incidence. Resonance shifts as a result of biosensing, such as DNA immobilization and hybridization, overall decrease with curvature and perpendicular incidence is more robust with a curvature change. The approach was extended to multi-curvature structure and finds significant fluctuation of resonance shift for parallel light incidence. The study can be of profound importance for plasmonic devices using flexible substrates and in fiber-based in vivo applications. PMID- 27410122 TI - Survival of the orbital angular momentum of light through an extraordinary optical transmission process in the paraxial approximation. AB - We report on the extraordinary optical transmission (EOT) of an orbital angular momentum (OAM) state of light in the paraxial approximation. The OAM state transmits through a subwavelength metal hole array with a square structure, and then is analyzed by using a Mach-Zehnder interferometer. In the experiment, the transmitted light well conserves the OAM information while the transmission efficiency of the OAM mode is much greater than 1 (i.e., EOT works). Further study shows that the OAM mode has no significant influence on the transmission spectrum of the EOT paraxial process under our experimental configuration. Our work can be useful for future plasmon-based OAM devices. PMID- 27410123 TI - Laser differential confocal radius measurement method for the cylindrical surfaces. AB - This paper proposes a laser differential confocal cylindrical radius of curvature measurement (DCCRM) method for high accuracy measurement of the radius of curvature of the cylindrical lens. Based on the property that the null point of an axial intensity curve precisely corresponds to the focus of the objective in a differential confocal system (DCS), the DCCRM uses the null point of the DCS axial intensity curve to precisely identify the cat's eye position and confocal position of the test cylindrical lens. The distance between the two positions is measured accurately using a laser distance instrument, thus achieving high precision radius measurement. In comparison with existing measurement methods, the proposed DCCRM has high measurement precision and strong environmental anti interference capability. Theoretical analyses and preliminary experimental results indicate that the DCCRM has a relative measurement uncertainty of better than 0.03% and provides a new approach for a high precision radius measurement of the cylindrical lens. PMID- 27410125 TI - Efficient 750-nm LED-pumped Nd:YAG laser. AB - We report an Nd:YAG laser pumped by light emission diodes (LEDs) at 750 nm. With 1% output coupling from a linear cavity containing a 2-cm long Nd:YAG crystal, the laser generated 37.5 MUJ pulse energy at 1064 nm with M2 = 1.1 when pumped by 2.73-mJ LED energy in a 1-ms pulse at a 10 Hz rate. The measured optical and slope efficiencies for this linear-cavity laser are 1.36, and 9%, respectively. With 1 and 5% output couplings from a Z-cavity containing the same laser crystal, the lasers generated 346 and 288 MUJ pulse energy with an optical efficiency of 3.4 and 2.8% and slope efficiency of 6.6 and 14%, respectively, for the same 1-ms pump pulse repeating at a 10 Hz rate. At the highest output from the Z-cavity, the measured M2 for the beam is 3.6. PMID- 27410124 TI - Generic precise augmented reality guiding system and its calibration method based on 3D virtual model. AB - Augmented reality system can be applied to provide precise guidance for various kinds of manual works. The adaptability and guiding accuracy of such systems are decided by the computational model and the corresponding calibration method. In this paper, a novel type of augmented reality guiding system and the corresponding designing scheme are proposed. Guided by external positioning equipment, the proposed system can achieve high relative indication accuracy in a large working space. Meanwhile, the proposed system is realized with a digital projector and the general back projection model is derived with geometry relationship between digitized 3D model and the projector in free space. The corresponding calibration method is also designed for the proposed system to obtain the parameters of projector. To validate the proposed back projection model, the coordinate data collected by a 3D positioning equipment is used to calculate and optimize the extrinsic parameters. The final projecting indication accuracy of the system is verified with subpixel pattern projecting technique. PMID- 27410126 TI - Coherent scattering microscopy as an effective inspection tool for analyzing performance of phase shift mask. AB - The imaging performance of a half-tone phase shift mask (PSM) has been analyzed using coherent scattering microscopy (CSM), which allows analysis of the actinic characteristics of an extreme ultraviolet (EUV) mask such as its reflectivity, diffraction efficiency, and phase information. This paper presents the 1st experimental result showing the effect of 180 degrees phase difference between the absorber and reflector in EUV mask. This reveals that a PSM offers a 46% improvement in 1st/0th diffraction efficiency and 14% improvement in image contrast when compared to a binary intensity mask (BIM). The horizontal-vertical critical dimension (H-V CD) bias is also reduced by 1.37 nm at 22 nm line and space (L/S) patterns. Since the performance of PSM can be evaluated without a wafer patterning process, CSM is expected to be a useful inspection tool for the development of novel EUV masks. PMID- 27410127 TI - 10.8 kW spectral beam combination of eight all-fiber superfluorescent sources and their dispersion compensation. AB - We report an 8-element spectral beam combination of Yb-doped all fiber superfluorescent sources around 1070 nm wavelength. Each source consists of a 60 mW front-end and a 1.5 kW three-stage fiber amplifier chain. The eight output beamlets are spectrally combined using a home-made polarization-independent multilayer dielectric reflective diffraction grating. 10.8 kW output power is achieved with an efficiency of 94%. Besides, both theoretical and experimental studies of dual grating dispersion compensation scheme have been performed, which is proved to be a prospective way for high brightness spectral beam combination. PMID- 27410128 TI - 100 W dissipative soliton resonances from a thulium-doped double-clad all-fiber format MOPA system. AB - In this paper, we first achieve nanosecond-scale dissipative soliton resonance (DSR) generation in a thulium-doped double-clad fiber (TDF) laser with all anomalous-dispersion regime, and also first scale the average power up to 100.4 W by employing only two stage TDF amplifiers, corresponding to gains of 19.3 and 14.4 dB, respectively. It is noted that both the fiber laser oscillator and the amplification system employ double-clad fiber as the gain medium for utilizing the advantages in high-gain-availability, high-power-handling and good-mode quality-maintaining. DSR mode-locking of the TDF oscillator is realized by using a nonlinear optical loop mirror (NOLM), which exhibits all-fiber-format, high nonlinear and passive saturable absorption properties. The TDF oscillator can deliver rectangular-shape pulses with duration ranging from ~3.74 to ~72.19 ns while maintaining a nearly equal output peak power level of ~0.56 W, namely peak power clamping (PPC) effect. Comparatively, the two stage amplifiers can scale the seeding pulses to similar average power levels, but to dramatically different peak powers ranging from ~0.94 to ~18.1 kW depending on the durations. Our TDF master-oscillator-power-amplifier (MOPA) system can provide a high power 2-MUm band all-fiber-format laser source both tunable in pulse duration and peak power. PMID- 27410129 TI - Stimulated Brillouin scattering and Brillouin-coupled four-wave-mixing in a silica microbottle resonator. AB - We report the first observation of stimulated Brillouin scattering (SBS) with Brillouin lasing, and Brillouin-coupled four-wave-mixing (FWM) in an ultra-high-Q silica microbottle resonator. The Brillouin lasing was observed at the frequency of OmegaB = 2pi * 10.4 GHz with a threshold power of 0.45 mW. Coupling between Brillouin and FWM was observed in both backward and forward scattering directions with separations of 2OmegaB. At a pump power of 10 mW, FWM spacing reached to 7th and 9th order anti-Stokes and Stokes, respectively. PMID- 27410130 TI - Reconfigurable lattice mesh designs for programmable photonic processors. AB - We propose and analyse two novel mesh design geometries for the implementation of tunable optical cores in programmable photonic processors. These geometries are the hexagonal and the triangular lattice. They are compared here to a previously proposed square mesh topology in terms of a series of figures of merit that account for metrics that are relevant to on-chip integration of the mesh. We find that that the hexagonal mesh is the most suitable option of the three considered for the implementation of the reconfigurable optical core in the programmable processor. PMID- 27410131 TI - Theoretical and experimental analysis of excessively tilted fiber gratings. AB - We have theoretically and experimentally investigated the dual-peak feature of tilted fiber gratings with excessively tilted structure (named as Ex-TFGs). We have explained the dual-peak feature by solving eigenvalue equations for TM0m and TE0m of a circular waveguide, in which the TE (transverse electric) and TM (transverse magnetic) core modes are coupled into TE and TM cladding modes, respectively. Meanwhile, in the experiment, we have verified that one of the dual peaks at the shorter wavelength is due to the TM mode coupling whereas the other one at the longer wavelength arises from TE mode coupling when a linearly polarized light launched into the Ex-TFG. We have also investigated the peak separation of TE and TM cladding mode for different surrounding medium refractive indexes (SRI), revealed that the dual peaks separation is decreasing as increasing of SRI, which agrees very well with the theoretical analysis results. PMID- 27410132 TI - High-resolution speckle imaging through strong atmospheric turbulence. AB - We demonstrate that high-resolution imaging through strong atmospheric turbulence can be achieved by acquiring data with a system that captures short exposure ("speckle") images using a range of aperture sizes and then using a bootstrap multi-frame blind deconvolution restoration process that starts with the smallest aperture data. Our results suggest a potential paradigm shift in how we image through atmospheric turbulence. No longer should image acquisition and post processing be treated as two independent processes: they should be considered as intimately related. PMID- 27410133 TI - Camera-based speckle noise reduction for 3-D absolute shape measurements. AB - Simultaneous position and velocity measurements enable absolute 3-D shape measurements of fast rotating objects for instance for monitoring the cutting process in a lathe. Laser Doppler distance sensors enable simultaneous position and velocity measurements with a single sensor head by evaluating the scattered light signals. The superposition of several speckles with equal Doppler frequency but random phase on the photo detector results in an increased velocity and shape uncertainty, however. In this paper, we present a novel image evaluation method that overcomes the uncertainty limitations due to the speckle effect. For this purpose, the scattered light is detected with a camera instead of single photo detectors. Thus, the Doppler frequency from each speckle can be evaluated separately and the velocity uncertainty decreases with the square root of the number of camera lines. A reduction of the velocity uncertainty by the order of one magnitude is verified by the numerical simulations and experimental results, respectively. As a result, the measurement uncertainty of the absolute shape is not limited by the speckle effect anymore. PMID- 27410134 TI - Second harmonic generation at 399 nm resonant on the 1S0 1P1 transition of ytterbium using a periodically poled LiNbO3 waveguide. AB - We demonstrate a compact and robust method for generating a 399-nm light resonant on the 1S0 - 1P1 transition in ytterbium using a single-pass periodically poled LiNbO3 waveguide for second harmonic generation (SHG). The obtained output power at 399 nm was 25 mW when a 798-nm fundamental power of 380 mW was coupled to the waveguide. We observed no degradation of the SHG power for 13 hours with a low power of 6 mW. The obtained SHG light has been used as a seed light for injection locking, which provides sufficient power for laser cooling ytterbium. PMID- 27410135 TI - Subwavelength topological structures resulting from surface two-plasmon resonance by femtosecond laser exposure solid surface. AB - We present that surface two-plasmon resonance (STPR) in electron plasma sheet produced by a femtosecond laser irradiating a solid surface is the self-formation mechanism of periodic subwavelength ripple structures. Peaks of overdense electrons, formed by resonant two-plasmon wave mode, pull bound ions out of the metal surface. Thus, the wave pattern of STPR is "carved" on the surface by Coulomb ablation (removal) due to periodic distributed strong electrostatic field produced by charge separation. To confirm the STPR model, we have performed analogical carving experiments by two femtosecond laser beams with perpendicular polarizations and time delay. The results explicitly show that two wave patterns of STPR generated by each beam are independently created in the pulse exposure area of a target surface, which is like the traditional "layer-carving" technique by comparison with the structured topological features. The time-scale of ablation dynamics and the electron temperature in ultrafast interaction are also verified by a time-resolved spectroscopy experiment and numerical simulation, respectively. The present model can self-consistently explain the formation of subwavelength ripple structures even with spatial periods shorter than half of the laser wavelength, shedding light on the understanding of ultrafast laser solid interaction. PMID- 27410136 TI - Biosensor architecture for enhanced disease diagnostics: lab-in-a-photonic crystal. AB - A conceptual lab-in-a-photonic-crystal biosensor is demonstrated that can multiplex four or more distinct disease-markers and distinguish their presence and combinations simultaneously with unique spectral fingerprints. This biosensor consists of a photonic-band-gap, multi-mode waveguide coupled to surface modes on either side, encased in a glass slide with microfluidic channels. The spectral fingerprints consist of multiple peaks in optical transmission vs. frequency that respond sensitively and uniquely in both frequency shift and nonmonotonic change of peak transmittance levels to various analyte bindings. This special property enables complete, logical determination of twelve different combinations of four distinct disease-markers through one scan of the transmission spectrum. The results reveal unique phenomena such as switching between the strong-coupling and weak-coupling combinations of surface states by analyte binding at different locations along the central waveguide. The unconventional transmission spectra are explained using a Landauer-Buttiker, multiple-scattering, transmission theory that reproduces the main features of the exact finite-difference-time-domain simulation. PMID- 27410137 TI - Characterization of Rayleigh backscattering arising in various two-mode fibers. AB - We experimentally characterize the mode dependent characteristics of Rayleigh backscattering (RB) arising in various two-mode fibers (TMFs). With the help of an all-fiber photonic lantern, we are able to measure the RB power at individual modes. Consequently, mode dependent power distribution of RB light caused by arbitrary forward propagation mode superposition can be obtained. The total RB power of the TMFs under test is higher than that of single mode fiber by at least 2 dB over the C band. Meanwhile, the RB light occurs among all guided modes in the TMFs with specific power ratios. The experimental characterization agrees well with the theoretical calculations. PMID- 27410138 TI - Impact of local-field effects on the plasmonic enhancement of vibrational signals by infrared nanoantennas. AB - We have developed an analytical model that provides a mechanistic description of the plasmonic enhancement of vibrational signals by infrared nanoantennas. Our treatment is based on a coupled-point-dipole model which considers the interaction between a point-like nanoantenna and a single vibrational dipole moment. This idealized model is refined in two consecutive steps. The first step generalizes the model to make the treatment of non-point-like nanoantennas possible. The second step deals with local-field effects originating from the mutual interaction of the molecular vibrations. We have compared the results of our model with finite-difference time-domain simulations, and we find that our model predicts both the lineshapes and the amplitudes of the vibrational signals in a quantitative manner. Our analysis shows that the local-field effects play a surprisingly dominant role in the plasmonic enhancement, and we discuss possibilities of engineering this local field in order to further boost the plasmonic amplification. PMID- 27410139 TI - Bending-induced mode non-degeneracy and coupling in chalcogenide negative curvature fibers. AB - We study bend loss in chalcogenide negative curvature fibers with different polarizations, different tube wall thicknesses, and different bend directions relative to the mode polarization. The coupling between the core mode and tube modes induces bend loss peaks in the two non-degenerate modes at the same bend radius. There is as much as a factor of 28 difference between the losses of the two polarization modes. The fiber with a larger tube wall thickness, corresponding to a smaller inner tube diameter, can sustain a smaller bend radius. The bend loss is sensitive to the bend direction when coupling occurs between the core mode and tube modes. A bend loss of 0.2 dB/m at a bend radius of 16 cm, corresponding to 0.2 dB/turn, can be achieved in a chalcogenide negative curvature fiber. PMID- 27410140 TI - Small phase pattern 2D beam steering and a single LCOS design of 40 1 * 12 stacked wavelength selective switches. AB - Two-dimensional beam steering by small, square, phase patterns as small as 50 * 50 pixels on a phase-only liquid crystal on silicon (LCOS) device is experimentally verified as suitable for the application of wavelength selective switches (WSSs), in terms of the diffraction efficiency and steering accuracy. This enables a proposed highly functional and versatile stacked switch architecture, where 40 independent 1 * 12 WSSs can be realised on a single 4k LCOS device. They can be configured to support a 1 * N WSSs with N<=144, or an N * N wavelength crossconnect with N<=12. PMID- 27410141 TI - LEO-to-ground polarization measurements aiming for space QKD using Small Optical TrAnsponder (SOTA). AB - Quantum communication, and more specifically Quantum Key Distribution (QKD), enables the transmission of information in a theoretically secure way, guaranteed by the laws of quantum physics. Although fiber-based QKD has been readily available since several years ago, a global quantum communication network will require the development of space links, which remains to be demonstrated. NICT launched a LEO satellite in 2014 carrying a lasercom terminal (SOTA), designed for in-orbit technological demonstrations. In this paper, we present the results of the campaign to measure the polarization characteristics of the SOTA laser sources after propagating from LEO to ground. The most-widely used property for encoding information in free-space QKD is the polarization, and especially the linear polarization. Therefore, studying its behavior in a realistic link is a fundamental step for proving the feasibility of space quantum communications. The results of the polarization preservation of two highly-polarized lasers are presented here, including the first-time measurement of a linearly-polarized source at lambda = 976 nm and a circularly-polarized source at lambda = 1549 nm from space using a realistic QKD-like receiver, installed in the Optical Ground Station at the NICT Headquarters, in Tokyo, Japan. PMID- 27410142 TI - Vapor sensing with a natural photonic cell. AB - Photonic structures encased by a permeable envelope give rise to iridescent blue color in the scales covering the male Hoplia coerulea beetle. This structure comprises a periodic porous multilayer. The color of these scales is known for changing from blue to green upon contact with water despite the presence of the envelope. This optical system has been referred to as a photonic cell due to the role of the envelope that mediates fluid exchanges with the surrounding environment. Following from previously studied liquid-induced changes in the color appearance of H. coerulea, we measured vapor-induced color changes in its appearance. This response to vapor exposure was marked by reflectance redshift and an increase in peak reflectance intensity. Different physico-chemical processes were investigated to explain the increase in reflectance intensity, a property not usually associated with vapor-induced optical signature changes. These simulations indicated the optical response arose from physisorption of a liquid film on the beetle scales followed by liquid penetration through the envelope and the filling of micropores within the body of the photonic structure. PMID- 27410143 TI - Excitation mechanism of A1g mode and origin of nonlinear temperature dependence of Raman shift of CVD-grown mono- and few-layer MoS2 films. AB - MoS2 films are grown on SiO2/Si substrates by chemical vapor deposition. The vibrational properties of optical phonons of mono-, bi- and multilayer MoS2 are studied by Raman scattering spectroscopy over temperature range from 90 to 540 K with 514.5 nm and 785 nm lasers. The Raman peaks of E2g1 and A1g modes are observed simultaneously for mono-, bi- and multilayer MoS2 with 514.5 nm laser, but only the Raman peak of E2g1 mode is seen for monolayer MoS2 as 785 nm laser is used, revealing electron-phonon exchange excitation mechanism of A1g mode for the first time. The Raman shifts of E2g1 and A1g modes present obvious nonlinear temperature dependence. A semi-quantitative model is used to fit the nonlinear temperature dependence of Raman shifts which matches well to experimental data. Meanwhile, the fitting results reveal that the nonlinear temperature dependence of Raman shifts of E2g1 mode mainly originates from three phonon anharmonic effect, while one of A1g mode is contributed by stronger three- and weaker four-phonon anharmonic effects cooperatively but two contributions are comparable in intensity. PMID- 27410144 TI - Deterministic generation of large scale atomic W states. AB - We present a deterministic scheme for generating large-scale atomic W states in a cavity QED system via a simple expansion mechanism, which is realized only by a detuned interaction between two identical atoms and a vacuum cavity mode. With the presented scheme, a W-type Bell pair can be created and an n-atom W state can be expanded to a 2n-atom W state with a unit probability of success in principle. No multi-atom gates, quantum memories or quantum non-demolition measurements are required, greatly simplifying the experimental realization of the scheme. The feasibility analysis shows that our expansion scheme can be implemented with state-of-the-art technologies. Our scheme enables advances not only in quantum information and communication but also in quantum thermodynamics, where atomic W states plays a crucial role. PMID- 27410145 TI - In situ spatial mapping of Gouy phase slip with terahertz generation in two-color field. AB - We establish a one-to-one mapping between the local phase slip and the spatial position near the focus by scanning a thin jet along the propagation direction of laser beams. The measurement shows that the optimal phase of terahertz can be utilized to characterize in situ the spatially dependent relative phase of the two-color field. We also investigate the role of the Gouy phase shift on terahertz generation from two-color laser-induced plasma. The result is of critical importance for phase-dependent applications of two-color laser-field, including high-order harmonic and terahertz generation. PMID- 27410146 TI - Software-defined optical network for metro-scale geographically distributed data centers. AB - The emergence of cloud computing and big data has rapidly increased the deployment of small and mid-sized data centers. Enterprises and cloud providers require an agile network among these data centers to empower application reliability and flexible scalability. We present a software-defined inter data center network to enable on-demand scale out of data centers on a metro-scale optical network. The architecture consists of a combined space/wavelength switching platform and a Software-Defined Networking (SDN) control plane equipped with a wavelength and routing assignment module. It enables establishing transparent and bandwidth-selective connections from L2/L3 switches, on-demand. The architecture is evaluated in a testbed consisting of 3 data centers, 5-25 km apart. We successfully demonstrated end-to-end bulk data transfer and Virtual Machine (VM) migrations across data centers with less than 100 ms connection setup time and close to full link capacity utilization. PMID- 27410147 TI - DFB fiber laser static strain sensor based on beat frequency interrogation with a reference fiber laser locked to a FBG resonator. AB - We report on a high-resolution static strain sensor developed with distributed feedback (DFB) fiber laser. A reference FBG resonator is used for temperature compensation. Locking another independent fiber laser to the resonator using the Pound-Drever-Hall technique results in a strain power spectral density better than Sepsilon(f) = (4.6 * 10-21) epsilon2/Hz in the frequency range from 1 Hz to 1 kHz, corresponding to a minimum dynamic strain resolution of 67.8 pepsilon/?Hz. This frequency stabilized fiber laser is proposed to interrogate the sensing DFB fiber laser by the beat frequency principle. As a reasonable DFB fiber laser setup is realized, a narrow beat frequency line-width of 3.23 kHz and a high beat frequency stability of 0.036 MHz in 15 minutes are obtained in the laboratory test, corresponding to a minimum static strain resolution of 270 pepsilon. This is the first time that a sub-0.5 nepsilon level for static strain measurement using DFB fiber laser is demonstrated. PMID- 27410148 TI - Lasing from organic quasicrystal fabricated by seven- and nine-beam interference. AB - We demonstrate mirrorless lasers based on all organic nanostructure fabricated by seven- and nine-beam interference using low contrast material, holographic polymer dispersed liquid crystals (H-PDLC). A finite-difference time-domain (FDTD) simulation is used to study the transmission of quasicrystal. The wavelengths of lasing peak are determined by both of local structure of quasicrystal that the pumping light experienced as well as the photoluminescence of laser dye doped. Features of mirrorless laser from quasicrystal based on H PDLC include directional light source, low threshold, simple fabrication process, low cost and tunability. These properties make H-PDLC photonic quasicrystal promising for a new type of all organic miniature lasers. PMID- 27410149 TI - Long-distance synchronization of unidirectionally cascaded optomechanical systems. AB - Synchronization is of great scientific interest due to the abundant applications in a wide range of systems. We propose an all-optical scheme to achieve the controllable long-distance synchronization of two dissimilar optomechanical systems, which are unidirectionally coupled through a fiber with light. Synchronization, unsynchronization, and the dependence of the synchronization on driving laser strength and intrinsic frequency mismatch are studied based on the numerical simulation. Taking the fiber attenuation into account, we show that two optomechanical resonators can be unidirectionally synchronized over a distance of tens of kilometers. We also analyze the unidirectional synchronization of three optomechanical systems, demonstrating the scalability of our scheme. PMID- 27410150 TI - Novel orthogonal velocity polishing tool and its material removal characteristics from CVD SiC mirror surfaces. AB - A new and patented polishing tool called Orthogonal Velocity field Tool (OVT) was built and its material removal characteristics from Chemical Vapor Deposition Silicon Carbide (CVD SiC) mirror surfaces were investigated in this study. The velocity field of OVT is produced by rotating the bicycle type tool in the two orthogonal axes, and this concept is capable of producing a material removal foot print of pseudo Gaussian shapes. First for the OVT characterization, we derived a theoretical material removal model using distributions of pressure exerted onto the workpiece surface, relative speed between the tool and workpiece surface, and dwell time inside the tool- workpiece contact area. Second, using two flat CVD SiC mirrors that are 150 mm in diameter, we ran material removal experiments over machine run parameter ranging from 12.901 to 25.867 psi in pressure, from 0.086 m/sec to 0.147 m/sec tool in the relative speed, and 5 to 15 sec in dwell time. Material removal coefficients are obtained by using the in-house developed data analysis program. The resulting material removal coefficient varies from 3.35 to 9.46 um/psi hour m/sec with a mean value of 5.90 +/- 1.26(standard deviation). We describe the technical details of the new OVT machine, the data analysis program, the experiments, and the results together with the implications to the future development of the machine. PMID- 27410151 TI - Strong coupling between mid-infrared localized plasmons and phonons. AB - We numerically and experimentally demonstrate strong coupling between the mid infrared localized surface plasmon resonances supported by plasmonic metamaterials and the phonon vibrational resonances of polymethyl methacrylate (PMMA) molecules. The plasmonic resonances are tuned across the phonon resonance of PMMA molecules at 52 THz to observe the strong coupling, which manifests itself as an anti-crossing feature with two newly formed plasmon-phonon modes. It is also shown that the forbidden energy gap due to mode splitting is proportional to the overlapped optical power between the plasmonic resonance mode and the PMMA molecules, providing an effective approach for manipulating the coupling strength of light-matter interaction. PMID- 27410152 TI - Glass interposer for short reach optical connectivity. AB - We propose a glass interposer containing femtosecond laser-scribed waveguides to interconnect silicon photonic chips. The glass interposer has an insertion loss of about 1.5 dB/cm, and simplifies alignment of silicon photonic chips. Our experiment shows that the insertion loss for the grating coupler/inscribed glass interface was only 0.5 dB higher than the estimated coupling loss of grating coupler to SMF. The 3 dB coupling degradation occurs after 5 um of in-plane displacement between the laser-inscribed waveguide and the grating coupler. PMID- 27410153 TI - Experimental generation of amplitude squeezed vector beams. AB - We present an experimental method for the generation of amplitude squeezed high order vector beams. The light is modified twice by a spatial light modulator such that the vector beam is created by means of a collinear interferometric technique. A major advantage of this approach is that it avoids systematic losses, which are detrimental as they cause decoherence in continuous-variable quantum systems. The utilisation of a spatial light modulator (SLM) gives the flexibility to switch between arbitrary mode orders. The conversion efficiency with our setup is only limited by the efficiency of the SLM. We show the experimental generation of Laguerre-Gauss (LG) modes with radial indices 0 or 1 and azimuthal indices up to 3 with complex polarization structures and a quantum noise reduction up to -0.9dB+/-0.1dB. The corresponding polarization structures are studied in detail by measuring the spatial distribution of the Stokes parameters. PMID- 27410154 TI - High resolution corneal and single pulse imaging with line field spectral domain optical coherence tomography. AB - We report the development of a Spectral Domain Line Field Optical Coherence Tomography (LF-OCT) system, using a broad bandwidth and spatial coherent Super Continuum (SC) source. With conventional quasi-Continuous Wave (CW) setup we achieve axial resolutions up to 2.1 MUm in air and 3D volume imaging speeds up to 213 kA-Scan/s. Furthermore, we report the use of a single SC pulse, of 2 ns duration, to temporally gate an OCT B-Scan image of 70 A-Scans. This is the equivalent of 35 GA-Scans/s. We apply the CW setup for high resolution imaging of the fine structures of a human cornea sample ex-vivo. The single pulse setup is applied to imaging of a coated pharmaceutical tablet. The fixed pattern noise due to spectral noise is removed by subtracting the median magnitude A-Scan. We also demonstrate that the Fourier phase can be used to remove aberration caused artefacts. PMID- 27410155 TI - Coherent octave-spanning mid-infrared supercontinuum generated in As2S3-silica double-nanospike waveguide pumped by femtosecond Cr:ZnS laser. AB - A more than 1.5 octave-spanning mid-infrared supercontinuum (1.2 to 3.6 MUm) is generated by pumping a As2S3-silica "double-nanospike" waveguide via a femtosecond Cr:ZnS laser at 2.35 MUm. The combination of the optimized group velocity dispersion and extremely high nonlinearity provided by the As2S3-silica hybrid waveguide enables a ~100 pJ level pump pulse energy threshold for octave-spanning spectral broadening at a repetition rate of 90 MHz. Numerical simulations show that the generated supercontinuum is highly coherent over the entire spanning wavelength range. The results are important for realization of a high repetition rate octave-spanning frequency comb in the mid-infrared spectral region. PMID- 27410156 TI - Rayleigh radiance computations for satellite remote sensing: accounting for the effect of sensor spectral response function. AB - To understand and assess the effect of the sensor spectral response function (SRF) on the accuracy of the top of the atmosphere (TOA) Rayleigh-scattering radiance computation, new TOA Rayleigh radiance lookup tables (LUTs) over global oceans and inland waters have been generated. The new Rayleigh LUTs include spectral coverage of 335-2555 nm, all possible solar-sensor geometries, and surface wind speeds of 0-30 m/s. Using the new Rayleigh LUTs, the sensor SRF effect on the accuracy of the TOA Rayleigh radiance computation has been evaluated for spectral bands of the Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi National Polar-orbiting Partnership (SNPP) satellite and the Joint Polar Satellite System (JPSS)-1, showing some important uncertainties for VIIRS-SNPP particularly for large solar- and/or sensor-zenith angles as well as for large Rayleigh optical thicknesses (i.e., short wavelengths) and bands with broad spectral bandwidths. To accurately account for the sensor SRF effect, a new correction algorithm has been developed for VIIRS spectral bands, which improves the TOA Rayleigh radiance accuracy to ~0.01% even for the large solar-zenith angles of 70 degrees -80 degrees , compared with the error of ~0.7% without applying the correction for the VIIRS-SNPP 410 nm band. The same methodology that accounts for the sensor SRF effect on the Rayleigh radiance computation can be used for other satellite sensors. In addition, with the new Rayleigh LUTs, the effect of surface atmospheric pressure variation on the TOA Rayleigh radiance computation can be calculated precisely, and no specific atmospheric pressure correction algorithm is needed. There are some other important applications and advantages to using the new Rayleigh LUTs for satellite remote sensing, including an efficient and accurate TOA Rayleigh radiance computation for hyperspectral satellite remote sensing, detector-based TOA Rayleigh radiance computation, Rayleigh radiance calculations for high altitude lakes, and the same Rayleigh LUTs are applicable for all satellite sensors over the global ocean and inland waters. The new Rayleigh LUTs have been implemented in the VIIRS-SNPP ocean color data processing for routine production of global ocean color and inland water products. PMID- 27410157 TI - Coded aperture correlation holography-a new type of incoherent digital holograms. AB - We propose and demonstrate a new concept of incoherent digital holography termed coded aperture correlation holography (COACH). In COACH, the hologram of an object is formed by the interference of light diffracted from the object, with light diffracted from the same object, but that passes through a coded phase mask (CPM). Another hologram is recorded for a point object, under identical conditions and with the same CPM. This hologram is called the point spread function (PSF) hologram. The reconstructed image is obtained by correlating the object hologram with the PSF hologram. The image reconstruction of multiplane object using COACH was compared with that of other equivalent imaging systems, and has been found to possess a higher axial resolution compared to Fresnel incoherent correlation holography. PMID- 27410158 TI - Demanding response time requirements on coherent receivers due to fast polarization rotations caused by lightning events. AB - Lightning events can cause fast polarization rotations and phase changes in optical transmission fibers due to strong electrical currents and magnetic fields. Whereas these are unlikely to affect legacy transmission systems with direct detection, different mechanisms have to be considered in systems with local oscillator based coherent receivers and digital signal processing. A theoretical analysis reveals that lightning events can result in polarization rotations with speeds as fast as a few hundred kRad/s. We discuss possible mechanisms how such lightning events can affect coherent receivers with digital signal processing. In experimental investigations with a high current pulse generator and transponder prototypes, we observed post FEC errors after polarization rotation events which can be expected from lightning strikes. PMID- 27410159 TI - Infrared amplified spontaneous emission from the 0 ((3)P0) and 0 ((1)D2) ion-pair states of molecular bromine. AB - We report the observation of amplified spontaneous emission for the first time from the 0 ((3)P0) and 0 ((1)D2) ion-pair states of Br2 by using an optical optical double resonance technique through the B (3)Pi(0) valence state as the intermediate state. The strong infrared emission propagating along the incident laser radiation is assigned to the parallel ASE transitions from the 0 ion-pair states down to the nearby 0 ion-pair states. The subsequent UV fluorescence from the 0 states to the high vibrational levels of the ground state is also observed. By the Franck-Condon simulation of the cascade UV fluorescence, we determine the vibrational distributions in the 0 states populated by ASE, which are consistent with the intensity distribution in the dispersed infrared ASE spectrum. The lifetimes of the relevant ion-pair states are evaluated by analyzing the temporal profiles of the UV fluorescence. PMID- 27410160 TI - A New, Dispersion-Driven Intermolecular Arrangement for the Benzene-Water Octamer Complex: Isomers and Analysis of their Vibrational Spectra. AB - The anharmonic spectra of the gas phase cubic water octamer (W8, D2d and S4 isomers) have been theoretically calculated at the second order Moller-Plesset perturbation (MP2) and the coupled cluster with single, double and a perturbative estimate of triple replacements [CCSD(T)] theories. The CCSD(T) harmonic frequencies are the first ones reported for this cluster. An additional band at ~3500 cm(-1) is reported, in a spectral area that was not previously accessible experimentally due to technical reasons. The IR spectra of the S4 isomer have a larger number of fundamental bands than the spectra of the D2d isomer, in accordance with the presence of lower symmetry in the former compared to the latter. When W8 interacts with benzene (BZ), the dispersion interaction plays a major role in determining the resulting intermolecular arrangement. Calculations at the MP2, DFT (with the omegaB97XD functional which includes dispersion corrections) and CCSD(T) levels of theory suggest an optimal arrangement in which BZ is almost parallel to one of the faces of the W8 cube. This structure differs from the previously reported one in which one of the "free" OH bonds of the W8 cube pointed toward the center of BZ (Science 276, 1678 (1997)) that was determined at the DFT level with the dispersionless B3LYP functional and was used to assign the experimentally measured IR spectra. Five low-lying isomers, three of the S4-like and two of the D2d-like type, were determined, and their spectra were assigned. The perturbation of BZ to the W8 vibrational bands amounts to (i) the localization of the normal modes of W8 thus resulting in more IR active bands and (ii) the lowering of the overall symmetry of the complex that results in the splitting of the doubly degenerate bands of the bare W8. Our results further suggest that a future recording of the IR spectra in the HOH bending region can definitively aid in the assignment of the various isomers of both the BZ and the BZ-W8 complexes. PMID- 27410161 TI - Dynamometry for the measurement of grip, pinch, and trunk muscles strength in subjects with subacute stroke: reliability and different number of trials. AB - Background: Muscle strength is usually measured in individuals with stroke with Portable dynamometers (gold standard). However, no studies have investigated the reliability, the standard error of measurement (SEM) and the minimal detectable difference (MDD95%) of the dynamometry for the measurement of hand grip, pinch grip and trunk strength in subjects with subacute stroke. Objective: 1) To investigate the intra and inter-rater reliability, the SEM and the MDD95% of the portable dynamometers for the measurement of grip, pinch and trunk strength in subjects with subacute stroke, and 2) to verify whether the use of different number of trials (first trial and the average of the first two and three trials) affected the results. Method: 32 subjects with subacute stroke (time since stroke onset: 3.6 months, SD=0.66 months) were evaluated. Hand grip, 3 pinch grips (i.e. pulp-to-pulp/palmar/lateral) and 4 trunk muscles (i.e. flexors, extensors, lateral flexors and rotators) strength were bilaterally assessed (except trunk flexors/extensors) with portable dynamometry by two independent examiners over two sessions (1-2 weeks apart). One-way ANOVAs and intraclass correlation coefficients (ICC2,k) were used for analysis (alpha=0.05). SEM and MDD95% were also calculated. Results: For all muscular groups and sources of outcome values, including one trial, after familiarization, similar results were found (0.01<=F<=0.08; 0.92<=p<=0.99) with significant and adequate values of intra rater (0.64<=ICC<=0.99; 0.23<=95%CI<=0.99) and inter-rater (0.66<=ICC<=0.99; 0.25<=95%CI<=0.99) reliability. SEM and MDD95% were considered low (0.39<=EPM<=2.21 Kg; 0.96<=MMD95%<=6.12 Kg) for all outcome scores. Conclusion: Only one trial, following familiarization, demonstrated adequate intra-rater and inter-rater reliability of the portable dynamometers for the measurement of hand grip, pinch grip and trunk strength in subjects with subacute stroke. PMID- 27410162 TI - Effects of a progressive resistance exercise program with high-speed component on the physical function of older women with sarcopenic obesity: a randomized controlled trial. AB - Background: Sarcopenic obesity is associated with disability in older people, especially in women. Resistance exercises are recommended for this population, but their efficacy is not clear. Objective: To evaluate the effects of a progressive resistance exercise program with high-speed component on the physical function of older women with sarcopenic obesity. Method: Twenty-eight women 65 to 80 years old, with a body mass index >=30kg/m2 and handgrip strength <=21kg were randomly allocated to two groups. The experimental group underwent a 10-week resistance exercise program designed to improve strength, power, and endurance of lower-limb muscles, with open chain and closed chain exercises. The control group had their health status monitored through telephone calls. The primary outcomes were lower limb muscle performance measured by knee extensor strength, power and fatigue by isokinetic dynamometry, and mobility measured by the Short Physical Performance Battery and by gait velocity. The secondary outcome was health related quality of life assessed by the SF-36 Questionnaire. Results: The average rate of adherence was 85%, with few mild adverse effects. There were no significant between-group differences for any of the outcomes. Conclusion: In this study, a progressive resistance exercise program with high-speed component was not effective for improving the physical function of older women with sarcopenic obesity. PMID- 27410164 TI - 1,3-Dien-5-ynes: Versatile Building Blocks for the Synthesis of Carbo- and Heterocycles. AB - 1,3-Dien-5-ynes have been extensively used as starting materials for the synthesis of a wide number of different carbo- and heterocycles. The aim of this review is to give an overview of their utility in organic synthesis, highlighting the variety of compounds that can be directly accessed from single reactions over these systems. Thus, cycloaromatization processes are initially commented, followed by reactions directed toward the syntheses of five-membered rings, other carbocycles and, finally, heterocycles. The diverse methodologies that have been developed for the synthesis of each of these types of compounds from 1,3-dien-5 ynes are presented, emphasizing the influence of the reaction conditions and the use of additional reagents in the outcome of the transformations. PMID- 27410163 TI - Immediate and short-term effects of the combination of dry needling and percutaneous TENS on post-needling soreness in patients with chronic myofascial neck pain. AB - Background: Dry needling (DN) and percutaneous electrical nerve stimulation (PENS) are widely used techniques in the treatment of myofascial pain. Objective: To investigate the immediate and short-term effects of the combination of DN and PENS compared to DN alone on the upper trapezius muscle. Method: This is a 72 hour follow-up single-blinded randomized controlled trial. Sixty-two volunteer patients with chronic myofascial neck pain with active Myofascial Trigger Points (MTrPs) in the upper trapezius muscle were recruited. Randomization was performed, and 31 patients received DN treatment (DN group) and 31 received DN and PENS (DN+PENS group). The primary outcomes were neck disability index (NDI) and visual analog scale for pain for both post-needling soreness (PNS) and neck pain intensity (NPI). Pressure pain threshold (PPT) and cervical range of motion (CROM) were the secondary outcomes. Results: We detected between-group differences in NPI and PNS in favor of the DN+PENS group immediately after treatment. No between-group differences in NDI were observed. Conclusion: PENS application after dry needling treatment is more effective than dry needling alone for decreasing soreness in the short term and improving neck pain intensity immediately in patients with myofascial chronic neck pain. PMID- 27410165 TI - Triggers for Violent Criminality in Patients With Psychotic Disorders. AB - IMPORTANCE: Absolute and relative risks of violence are increased in patients with psychotic disorders, but the contribution of triggers for violent acts to these risks is uncertain. OBJECTIVE: To examine whether a range of triggers for violent acts are associated with risks of violence in patients diagnosed with psychotic disorders and in individuals without a psychiatric diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Using a sample of all individuals born in Sweden between 1958 and 1988 (N = 3 123 724), we identified patients in the National Patient Register who were diagnosed with schizophrenia spectrum disorders (n = 34 903) and bipolar disorder (n = 29 692), as well as unaffected controls (n = 2 763 012). We then identified, within each subsample, persons who had experienced any of the following triggers for violent acts between January 1, 2001, and December 15, 2013: exposure to violence, parental bereavement, self-harm, traumatic brain injury, unintentional injuries, and substance intoxication. By using within individual models, we conducted conditional logistic regression to compare the risk of the individual engaging in violent acts in the week following the exposure to a trigger with the risk during earlier periods of equivalent length. All time-invariant confounders (eg, genetic and early environmental influences) were controlled for by this research design and we further adjusted for time varying sociodemographic factors. MAIN OUTCOMES AND MEASURES: Adjusted odds ratios (aORs) of violent crime occurring in the week following the exposure to a trigger event compared with earlier periods. RESULTS: Among the sample of 2 827 607 individuals (1 492 186 male and 1 335 421 female), all of the examined trigger events were associated with increased risk of violent crime in the week following exposure. The largest 1-week absolute risk of violent crime was observed following exposure to violence (70-177 violent crimes per 10 000 persons). For most triggers, the relative risks did not vary significantly by diagnosis, including unintentional injuries (aOR range, 3.5-4.8), self-harm (aOR range, 3.9-4.2), and substance intoxication (aOR range, 3.0-4.0). Differences by diagnosis included parental bereavement, which was significantly higher in patients with schizophrenia spectrum disorders (aOR, 5.0; 95% CI, 3.0-8.1) compared with controls (aOR, 1.7; 95% CI, 1.3-2.2). CONCLUSIONS AND RELEVANCE: In addition to identifying risk factors for violence, clarifying the timing of the triggers may provide opportunities to improve risk assessment and management in individuals with psychotic disorders. PMID- 27410166 TI - Circulating Microparticles Decrease After Cardiac Stress in Patients With Significant Coronary Artery Stenosis. AB - BACKGROUND: Cardiac stress leads to a dynamic increase of circulating microparticles (MPs) in healthy individuals that is diminished in individuals with vascular disease. The impact of coronary ischemia on circulating MP level is unknown. This study investigates the kinetics of circulating MPs during cardiac stress in patients with coronary artery stenosis. HYPOTHESIS: Patients with significant coronary stenosis show altered circulating MP levels after cardiac stress. METHODS: Eighty patients with stable coronary artery disease underwent dobutamine stress echocardiography (DSE) on the day before coronary angiography. Before, immediately after, at 4 hours, and at 24 hours after DSE, blood was drawn to determine CD144+ endothelial microparticles (EMPs), CD14+ CD16+ monocyte derived microparticles (MMPs), and CD31+ CD42b+ platelet microparticles. A significant stenosis was defined as stenosis diameter >=70% in a major native epicardial coronary artery with a diameter of >=2.5 mm. RESULTS: Significant coronary artery stenoses were found in 41 patients. In these patients, CD144+ EMP and CD14+ CD16+ -MMP concentrations decreased immediately after DSE. Stimulation of target endothelial cells with sera from patients with significant coronary artery stenoses significantly augmented endothelial capacity to take up EMPs, but not MMPs, in vitro. Serum-induced enhancement of endothelial phosphatidylserine receptor expression was found as a potential mechanism of increased endothelial EMP uptake and subsequently reduced circulating EMP levels after cardiac stress. CONCLUSIONS: Cardiac ischemia leads to reduced circulating MP levels under cardiac stress. Changes of endothelial MP uptake capacities could be one possible mechanism. PMID- 27410167 TI - Quality of Life and Burnout Rates Across Surgical Specialties: A Systematic Review. AB - Importance: Establishing strategies to minimize the burden of burnout and poor quality of life (QOL) on surgeons relies on a thorough understanding of QOL and burnout among the various surgical specialties. Objectives: To systematically review the literature across multiple surgical specialties and provide a comprehensive understanding of QOL and burnout among all surgeons, to delineate variation in rates of burnout and poor QOL, and to elucidate factors that are commonly implicated in these outcomes. Evidence Review: An OVID electronic search encompassing MEDLINE, PsycInfo, and EMBASE was completed using the following MeSH search terms: quality of life, burnout, surgeon, surgical specialty, and United States. Full articles published in English from January 1, 1980, to June 10, 2015, that evaluated US surgical specialists and included more than 1 question related to QOL were included. Review articles and evaluations that included medical students or nonsurgical health care professionals were excluded. Of 1420 titles, 41 articles met these criteria. The standardized methodologic principles of PRISMA for reporting systematic reviews guided analysis. Primary end points were QOL scores and burnout rates that compared sex, age, level of training (resident vs attending), surgical specialty, and the type of assessment tool. Secondary outcomes included proposed work hours and income as factors contributing to burnout. Owing to the heterogeneity of data reporting among articles, qualitative analysis was also reported. Findings: Of the 16 specialties included, pediatric (86% to 96%) and endocrine (96%) surgeons demonstrated the highest career satisfaction, whereas a portion of plastic surgeons (33%) and vascular surgeons (64%) were least satisfied. The effect of sex was variable. Residents demonstrated a significantly higher risk for burnout than attending surgeons across multiple specialties, including obstetrics and gynecology, otolaryngology, and orthopedic surgery. One-third of the studies found hours worked per week to be a statistically significant predictor of burnout, decreased career satisfaction, and poorer QOL. Conclusions and Relevance: Burnout and QOL vary across all surgical specialties. Whether sex affects burnout rates remains unclear. Residents are at an increased risk for burnout and more likely to report a poor QOL than attending surgeons. PMID- 27410168 TI - On the Origin of Dolabriferol: Total Synthesis via Its Putative Contiguous Precursor. AB - The putative contiguous polypropionate precursor of dolabriferol was synthesized using as the key step a rationally designed enantiomer-selective aldol coupling (i.e., with kinetic resolution) of a racemic C1-C8 ketone fragment with an enantiopure C9-C15 aldehyde fragment. When exposed to alumina, the precursor was cleanly transformed into dolabriferol via a regioselective retro-Claisen fragmentation, providing the first experimental evidence for the proposed origin of dolabriferol and demonstrating that it is a plausible isolation artifact. PMID- 27410169 TI - Comparison of three different options for immediate treatment of painful temporomandibular disorders: a randomized, controlled pilot trial. AB - OBJECTIVE: The purpose of this study was to compare the short-term effectiveness of three different types of immediate, non-pharmacological intervention for alleviation of the painful symptoms of temporomandibular disorders (TMD). MATERIAL AND METHODS: Thirty-six patients (mean age 41.6 +/- 16.7 years, 25 females) diagnosed with non-dysfunctional painful TMD received counselling and subsequently were randomly allocated to three treatment groups: patients in Group A received prefabricated oral splints with water-filled elastic pads (Aqualizer((r))), those in Group B were provided with vacuum-formed co-polyester oral splints and those in Group C were given appointments to receive Michigan type hard splints. Clinical examination was conducted, at baseline and after 2 weeks, by use of the RDC/TMD. Current pain intensity was determined by evaluation of graded chronic pain status (GCPS) on a numerical rating scale (NRS). Active maximum mouth opening without pain (AMMOP) was also measured. Paired sample t tests and one-way analysis of variance with a significance level of p <= 0.05 were conducted. RESULTS: After 2 weeks, overall mean current pain was reduced by 41.95% (p < 0.001). Current pain reduction was significant for Group B (66.6%, p < 0.001) but not for Groups A (37.88%, p = 0.56) and C (22.29%, p = 0.26). After 2 weeks, current pain level for Group B was significantly lower than that for Group C (p = 0.041). Overall, there was a statistically significant increase of AMMOP (p = 0.01). CONCLUSION: All therapeutic options were pain-reducing. The results from this study suggest that cost-effective and time-effective intervention of counselling combined with use of a vacuum-formed splint is a favourable option for initial, short-term treatment of painful TMD. PMID- 27410170 TI - Markets and Molecules: A Pharmaceutical Primer from the South. AB - The Indian pharmaceutical industry has historically manufactured low-cost drugs for the global poor. Activist mobilizations at the height of the HIV/AIDS epidemic revealed a vast cost gap between global brands and Indian generics, much to the embarrassment of Euro-American corporations that were in the habit of pricing drugs for only the wealthy or well insured. As new drug access controversies focus on anticancer therapies, they reveal new flows of international capital, emergent genetic technologies, and increasingly coercive trade regimes. Together these favor multinational corporate oligopolies, which imperil the legacy of HIV/AIDS activism and the future availability of essential life-saving drugs for the work of global public health. In this essay, I describe how the future of the right to drug access rests uneasily, and potentially calamitously, on a shifting balance of power between global south interests and Euro-American pharmaceutical capital. PMID- 27410171 TI - Depressive symptoms moderate the relationship between sleep quality and cognitive functions among the elderly. AB - OBJECTIVE: The co-occurrence of sleep problems, cognitive impairment, and depression among the elderly suggests that these three conditions are likely to be interrelated. Recent findings suggest that depressive symptoms moderate the relationship between sleep problems and cognitive impairment in elderly people but methodological problems have led to inconsistent conclusions. The present study aims to better understand the relationship between sleep quality, depressive symptoms, and cognitive function. METHOD: We administered the Repeatable Battery for the Assessment of Neuropsychological Status and self report measures of sleep quality and depression to 380 elderly participants (Mage = 68 years, SD= 5.7). Bootstrapped moderation analyses were conducted to examine the role of depressive symptoms in the relationship between sleep and various aspects of cognitive function. RESULTS: This moderation effect was significant in the domains of delayed memory (DeltaR(2) = .01, F = 4.5, p = .04), language (DeltaR(2) = .01, F = 4.6, p = .035), and general cognitive status (DeltaR(2) = .01, F = 5.3, p = .02). However, unlike previous studies, higher sleep quality corresponded to better outcomes in delayed memory, language abilities, and general cognitive status in participants with low levels of depressive symptoms. No significant relationship between sleep quality and any cognitive function was observed among participants with high levels of depressive symptoms. CONCLUSIONS: Among individuals who reported low levels of depressive symptoms, sleep quality was positively related to cognitive performance in the domains of delayed recall, language, and general cognitive status. However, sleep quality was not significantly associated with cognitive abilities in these domains among participants with elevated levels of depressive symptoms; participants had relatively poor outcomes in these cognitive domains regardless of their sleep quality. PMID- 27410172 TI - Robotic perineal radical prostatectomy and pelvic lymph node dissection using a purpose-built single-port robotic platform. AB - OBJECTIVES: To describe the features of the novel, purpose-built da Vinci model SP1098 single-port robotic platform and to describe a step-by-step approach for perineal prostatectomy and pelvic lymph node dissection in a cadaver model. METHODS: Three single-port robotic radical perineal prostatectomies and two pelvic lymph node dissections were performed on three male cadavers to assess the feasibility of the SP1098 da Vinci robotic platform. The steps in the procedure included division of the rectourethralis muscle, splitting of the levator ani muscles bilaterally, opening of Denonvilliers fascia with dissection of the seminal vesicles, apical dissection and urethral division, anterior and lateral dissection with ligation of prostatic pedicles, bilateral pelvic lymph node dissection, and creation of the new vesico-urethral anastomosis. The main outcomes assessed were operating time per step, total operating time, intra operative complications and need for conversion to conventional or open techniques. RESULTS: No conversions were required. No intra-operative complications were seen. The median (range) operating time for performing single port robotic radical perineal prostatectomy and pelvic lymph node dissection was 210 (180-240) min. CONCLUSIONS: We have shown the feasibility and efficacy of a novel, purpose-built robotic system in performing single-port radical perineal prostatectomy and describe, for the first time, the feasibility of robotic perineal lymph node dissection. This single-port system will facilitate single port applications and allow surgeons to perform major urological operations via a small, single incision while preserving triangulation and optics, and eliminating clashing between instruments. Future clinical studies are needed to support these encouraging outcomes. PMID- 27410173 TI - One-Electron Oxidation of Hydrogen Sulfide by a Stable Oxidant: Hexachloroiridate(IV). AB - Detailed reports on the oxidation of aqueous H2S by mild one-electron oxidants are lacking, presumably because of the susceptibility of these reactions to trace metal-ion catalysis and the formation of turbid sulfur sols. Here we report on the reaction of [IrCl6](2-) with H2S in acetate buffers. Dipicolinic acid (dipic) is shown to be effective in suppressing metal-ion catalysis. In the presence of dipic the reaction produces [IrCl6](3-) and polysulfides; turbidity develops primarily after the Ir(IV) oxidant is consumed. Water-soluble phosphines are shown to prevent the development of turbidity; in the case of tris hydroxymethylphosphine (THMP) the product is the corresponding sulfide, THMP?S. THMP diminishes the rates of reduction of Ir(IV), and the rate law with sufficient THMP is first order in [Ir(IV)] and first order in [HS(-)]. The rate limiting step is inferred to be electron transfer from HS(-) to Ir(IV) with ket = 2.9 * 10(4) M(-1) s(-1) at 25.0 degrees C and MU = 0.1 M. The kinetic inhibition by THMP is attributed to its interception of a polysulfide chain elongation process. PMID- 27410174 TI - Does family background impact driving attitudes and risky behaviours? An investigation on Chinese young drivers. AB - The rapid pace of motorisation in China has been well documented, as has the large road trauma burden the Chinese citizens are facing as a result. China's unique political system represents an important consideration in helping reduce road trauma, yet political factors have not been previously investigated in this context. Recently, emerging issues on the road involving the adult children of politically powerful families have become a serious social problem in China, and have drawn widespread media and public attention. This study took a novel approach to examining factors associated with risky attitudes and risky road use in China by investigating the economic and political background status of a sample of young Chinese drivers. An online survey was conducted in May 2015 with a sample size of 476 Chinese young drivers from across the country, aged between 18 and 28, including 305 males and 171 females. The results suggest that for participants who reported having a familial political background, more risky driving behaviours were reported among those participants who reported more impact on their life from that political background; while for participants without political background, higher personal income was associated with more risky driving behaviours. The findings are discussed in light of China's political management system and potential education opportunities for young drivers. PMID- 27410175 TI - The effect of a road safety educational program for kindergarten children on their parents' behavior and knowledge. AB - Road safety education for children is one of the most important means for raising awareness of road safety and for educating children to behave safely as pedestrians, bicycle riders, and vehicle passengers. The current research presents a novel attempt to examine the effect of a unique road safety educational program for kindergarten children on a secondary target group-the parents. The program, named the "Zahav Bagan" program (ZBP), is presented at kindergartens once a week during the entire academic year. It is conducted by senior citizen volunteers and is part of the formal education of the children. The main purpose of the current study was to compare the behavior, awareness, and knowledge about child road safety, of two groups of parents-those whose children participated in the ZBP group, and those whose children did not; this latter group was the control group. A telephone-based survey was conducted using a sample of 76 ZBP parents and 59 control group parents. Results of the survey showed no effect of ZBP on parents' knowledge of child road safety law and recommendations, but more importantly, the results did show a significant effect in terms of parents' observance of safe behavior and in their awareness of road safety in everyday life. These results confirm the importance of educational programs on road safety, especially as triggers and reminders to children and to their parents, to act as cautious road users. PMID- 27410176 TI - Transient scrotal hyperthermia affects human sperm DNA integrity, sperm apoptosis, and sperm protein expression. AB - This prospective randomized clinical study is aimed to evidence the reproductive impairment of frequent scrotal heat exposure. A total of 20 normozoospermic subjects were randomly divided into two groups to undergo testicular warming in a 43 degrees C water bath 10 times, for 30 min each time; the subjects in group 1 underwent testicular warming for 10 consecutive days and those in group 2 once every 3 days. Sperm chromatin structure assay (SCSA), sperm mitochondrial membrane potential (MMP), apoptosis, and seminal plasma-soluble Fas (sFas) were analyzed before treatment and every 2 weeks after, for a total of 10 times. In group 1, some critical proteins involved in heat stress, hypoxia, structure, and function of sperm mitochondria and flagella were evaluated before hyperthermia and 2, 6, 10, and 16 weeks after hyperthermia. Both groups showed a reversible increase in the proportion of spermatozoa with a disrupted MMP (both p < 0.05 when the minimums were compared with baseline levels, the same below), sperm apoptosis (both p < 0.01) and high DNA stainability (both p < 0.05). The sFas concentration in both groups showed no obvious changes except one: the value at week 2 was significantly increased over baseline in group 1 (p = 0.036). The level of Bcl-2 decreased significantly at weeks 6 and 10 (p = 0.017 and 0.05, respectively) and recovered to baseline at week 16. Proteins involved in heat stress and mitochondria functions were up-regulated, whereas in flagella structure and function was down-regulated (all p < 0.05). This study demonstrated that transient and frequent scrotal hyperthermia severely and reversibly damaged spermatogenesis, consecutive heat exposure had more serious effects than intermittent exposure, whereas intermittent exposure led to a later recovery of sperm damage. PMID- 27410177 TI - Minorities Are Underrepresented in Clinical Trials of Pharmaceutical Agents for Cystic Fibrosis. AB - RATIONALE: Members of racial or ethnic minorities make up an appreciable proportion of patients with cystic fibrosis (CF) and have worse outcomes than non Latino white individuals. Between 1,999 and 2014, the CF Foundation Patient Registry reported an increase in minorities from 5 to 8.2% for Latinos, from 3 to 4.6% for black individuals and from 1.4 to 3.1% for "Other." OBJECTIVES: To evaluate the representation of racial and ethnic minorities in pharmacology clinical trials for CF. METHODS: We analyzed pharmacology clinical trials in CF published between 1999 and 2015 by searching PubMed and published study reference lists for qualifying study reports. We examined whether the race and ethnicity of study subjects were reported and, if so, what percentage of subjects represented major minority groups. MEASUREMENTS AND MAIN RESULTS: Among 147 pharmacology clinical trials, only 19.7% reported the race or ethnicity of study subjects. Latinos were verified as included in 7.5% of clinical trials, black individuals in 6.8%, and Asians in 2.0%. Inclusion of subjects described as "Other race" was reported in 7.5% of trials. In 29 clinical trials that reported race and ethnicity, the percentage of minorities included as subjects was 2.0% for Latinos, 1.0% for black individuals, and 0.1% for Asians. CONCLUSIONS: Although CF disproportionately affects non-Latino white individuals, members of other racial or ethnic groups are proportionally underrepresented in CF pharmacology clinical trials. Inadequate inclusion of minorities and failure to report the racial or ethnic background of study subjects limits information about factors influencing drug response and may contribute to health disparities for minorities with CF. PMID- 27410179 TI - Coming in postgraduate medicine. PMID- 27410178 TI - Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R-PTH1R Mutations With or Without Overt Hypercalcemia. AB - CONTEXT: Jansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of PTH. Five different heterozygous activating PTH/PTHrP receptor (PTH1R) mutations that change one of three different amino acid residues are known to cause JMC. OBJECTIVES: Establishing the diagnosis of JMC during infancy or early childhood can be challenging, especially in the absence of family history and/or overt hypercalcemia. We therefore sought to provide radiographic findings supporting this diagnosis early in life. PATIENTS AND METHODS: Three patients, a mother and her two sons, had radiographic evidence for JMC. However, obvious hypercalcemia and suppressed PTH levels were encountered only in both affected children. Sanger sequencing and endonuclease (SphI) digestion of PCR-amplified genomic DNA were performed to search for the H223R-PTH1R mutation. RESULTS: The heterozygous H223R mutation was identified in all three affected individuals. Surprisingly, however, the now 38 year-old mother was never overtly hypercalcemic and was therefore not diagnosed until her sons were found to be affected by JMC at the ages of 28 months and 40 days, respectively. The presented radiographic findings at different ages will help diagnose other infants/toddlers suspected of having JMC. CONCLUSION: The H223R mutation is typically associated with profound hypercalcemia despite low/normal PTH levels. However, the findings presented herein show that overt hypercalcemia is not always encountered in JMC, even if caused by this relatively frequent mutation, which is similar to observations with other PTH1R mutations that show less constitutive activity. PMID- 27410181 TI - Problems solutions. PMID- 27410180 TI - Editor's mail. PMID- 27410183 TI - Washington background. PMID- 27410182 TI - What's happening in medicine. PMID- 27410184 TI - Physician-at-large. PMID- 27410187 TI - Therapeutic Index TO Advertisers. PMID- 27410185 TI - Raised Intracranial Pressure. AB - When intracranial hypertension is minimal to moderate in degree and insidious in onset, it may be asymptomatic. The clinical situation and the pathologic process responsible for the elevated pressure are the guides to selection of therapy. PMID- 27410188 TI - General Solution for Stabilizing Triple Helical Collagen. AB - One of the most ubiquitous stabilizing forces in nature is the hydrogen bond, exemplified by the folded secondary, tertiary, and higher-order structure of biomolecules. Despite the fundamental importance of hydrogen bonding, dependence on this stabilizing force places limitations on nature's proteinogenic building blocks. Herein, we demonstrate that replacement of the strictly conserved glycine in collagen with aza-glycine has profound consequences on the stability and self assembly of collagen peptides by providing an extra hydrogen bond donor. The additional hydrogen bond provided by aza-glycine allows for complete replacement of glycine residues in collagen peptides and truncation to the smallest self assembling collagen peptide systems observed to date. Our results highlight the vital importance of hydrogen bonding at desolvated interfaces, providing a new strategy for optimization of designed peptide materials and a general solution for stabilizing the collagen triple helix. PMID- 27410189 TI - Skin antisepsis for reducing central venous catheter-related infections. AB - BACKGROUND: The central venous catheter (CVC) is a device used for many functions, including monitoring haemodynamic indicators and administering intravenous medications, fluids, blood products and parenteral nutrition. However, as a foreign object, it is susceptible to colonisation by micro organisms, which may lead to catheter-related blood stream infection (BSI) and in turn, increased mortality, morbidities and health care costs. OBJECTIVES: To assess the effects of skin antisepsis as part of CVC care for reducing catheter related BSIs, catheter colonisation, and patient mortality and morbidities. SEARCH METHODS: In May 2016 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations and Epub Ahead of Print); Ovid EMBASE and EBSCO CINAHL Plus. We also searched clinical trial registries for ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed any type of skin antiseptic agent used either alone or in combination, compared with one or more other skin antiseptic agent(s), placebo or no skin antisepsis in patients with a CVC in place. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for their eligibility, extracted data and assessed risk of bias. We expressed our results in terms of risk ratio (RR), absolute risk reduction (ARR) and number need to treat for an additional beneficial outcome (NNTB) for dichotomous data, and mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: Thirteen studies were eligible for inclusion, but only 12 studies contributed data, with a total of 3446 CVCs assessed. The total number of participants enrolled was unclear as some studies did not provide such information. The participants were mainly adults admitted to intensive care units, haematology oncology units or general wards. Most studies assessed skin antisepsis prior to insertion and regularly thereafter during the in-dwelling period of the CVC, ranging from every 24 h to every 72 h. The methodological quality of the included studies was mixed due to wide variation in their risk of bias. Most trials did not adequately blind the participants or personnel, and four of the 12 studies had a high risk of bias for incomplete outcome data.Three studies compared different antisepsis regimens with no antisepsis. There was no clear evidence of a difference in all outcomes examined, including catheter-related BSI, septicaemia, catheter colonisation and number of patients who required systemic antibiotics for any of the three comparisons involving three different antisepsis regimens (aqueous povidone iodine, aqueous chlorhexidine and alcohol compared with no skin antisepsis). However, there were great uncertainties in all estimates due to underpowered analyses and the overall very low quality of evidence presented.There were multiple head-to-head comparisons between different skin antiseptic agents, with different combinations of active substance and base solutions. The most frequent comparison was chlorhexidine solution versus povidone-iodine solution (any base). There was very low quality evidence (downgraded for risk of bias and imprecision) that chlorhexidine may reduce catheter-related BSI compared with povidone-iodine (RR of 0.64, 95% CI 0.41 to 0.99; ARR 2.30%, 95% CI 0.06 to 3.70%). This evidence came from four studies involving 1436 catheters. None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine, alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality (and were generally underpowered). Mortality was only reported in a single study.There was very low quality evidence that skin antisepsis with chlorhexidine may also reduce catheter colonisation relative to povidone-iodine (RR of 0.68, 95% CI 0.56 to 0.84; ARR 8%, 95% CI 3% to 12%; ; five studies, 1533 catheters, downgraded for risk of bias, indirectness and inconsistency).Evaluations of other skin antiseptic agents were generally in single, small studies, many of which did not report the primary outcome of catheter-related BSI. Trials also poorly reported other outcomes, such as skin infections and adverse events. AUTHORS' CONCLUSIONS: It is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing. Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine. These results are based on very low quality evidence, which means the true effects may be very different. Moreover these results may be influenced by the nature of the antiseptic solution (i.e. aqueous or alcohol-based). Further RCTs are needed to assess the effectiveness and safety of different skin antisepsis regimens in CVC care; these should measure and report critical clinical outcomes such as sepsis, catheter-related BSI and mortality. PMID- 27410190 TI - Porous Organic Molecular Frameworks with Extrinsic Porosity: A Platform for Carbon Storage and Separation. AB - The assembly of porous organic molecular frameworks (POMFs), which typically evidence common feasibility and compatibility, purification, and regeneration at practical conditions, remains a strategic challenge in modern materials science and is crucial for their favorable applications in biological, medical, and environmental realms. However, instructive knowledge of well-organized POMF assembly by supramolecular interactions is, in general, ambiguous to date. Nevertheless, a significant advance in controlled POMF assembly has been recently achieved. This Minireview highlights these approaches, with a particular focus on the design of molecular constituents and assembly strategies. We also look beyond the field of solid-state POMF materials into the assembly and recognition in solution, thus covering recent advances in POMFs based on material design and applications in carbon storage and separation. PMID- 27410191 TI - Parameters influencing glenoid loosening. AB - INTRODUCTION: There is a lack of organization in existing studies on the outcome and complications of total shoulder arthroplasty. As a result, it is difficult to gain substantial evidence regarding the rate and risk factors for the occurrence of glenoid loosening which remains the most common cause of prosthetic failure. To improve the quality of future studies, an agreement should exist on definitions of glenoid loosening and on the potential risk factors. AREAS COVERED: Reviewing the literature, loosening can be defined as the appearance of radiolucent lines, radiological loosening, clinical loosening and revision as the end stage. Three different categories of influencing parameters can be distinguished: implant related, patient related and surgeon related. Expert commentary: The aim of this review is to organize the available knowledge on glenoid failure, as well as to describe the gaps so that it will constructively contribute to the debate on how to prevent glenoid failure in the anatomic total shoulder arthroplasty. PMID- 27410192 TI - Drastic Enhancement of Photocatalytic Activities over Phosphoric Acid Protonated Porous g-C3 N4 Nanosheets under Visible Light. AB - A simple method is developed to fabricate protonated porous graphitic carbon nitride nanosheets (P-PCNNS) by protonation-exfoliation of bulk graphitic carbon nitride (BCN) with phosphoric acid (H3 PO4 ). The H3 PO4 treatment not only helps to exfoliate the BCN into 2D ultrathin nanosheets with abundant micro- and mesopores, endowing P-PCNNS with more exposed active catalytic sites and cross plane diffusion channels to facilitate the mass and charge transport, but also induces the protonation of carbon nitride polymer, leading to the moderate removal of the impurities of carbon species in BCN for the optimization of the aromatic pi-conjugated system for better charge separation without changing its chemical structure. As a result, the P-PCNNS show much higher photocatalytic performance for hydrogen evolution and CO2 conversion than bare BCN and graphitic carbon nitride nanosheets. PMID- 27410195 TI - Facial malformation atlas aims to aid diagnosis of genetic disorders in patients of non-European descent: National Human Genome Research Institute launches online database of facial phenotypes targeting diverse populations. PMID- 27410196 TI - Gene therapy for severe combined immune deficiency poised for European approval: If green-lighted, Strimvelis would provide additional treatment option for second most common form of disease. PMID- 27410199 TI - Tough and Cell-Compatible Chitosan Physical Hydrogels for Mouse Bone Mesenchymal Stem Cells in Vitro. AB - Most hydrogels involve synthetic polymers and organic cross-linkers that cannot simultaneously fulfill the mechanical and cell-compatibility requirements of biomedical applications. We prepared a new type of chitosan physical hydrogel with various degrees of deacetylation (DDs) via the heterogeneous deacetylation of nanoporous chitin hydrogels under mild conditions. The DD of the chitosan physical hydrogels ranged from 56 to 99%, and the hydrogels were transparent and mechanically strong because of the extra intra- and intermolecular hydrogen bonding interactions between the amino and hydroxyl groups on the nearby chitosan nanofibrils. The tensile strength and Young's modulus of the chitosan physical hydrogels were 3.6 and 7.9 MPa, respectively, for a DD of 56% and increased to 12.1 and 92.0 MPa for a DD of 99% in a swelling equilibrium state. In vitro studies demonstrated that mouse bone mesenchymal stem cells (mBMSCs) cultured on chitosan physical hydrogels had better adhesion and proliferation than those cultured on chitin hydrogels. In particular, the chitosan physical hydrogels promoted the differentiation of the mBMSCs into epidermal cells in vitro. These materials are promising candidates for applications such as stem cell research, cell therapy, and tissue engineering. PMID- 27410200 TI - Designer Extracellular Matrix Based on DNA-Peptide Networks Generated by Polymerase Chain Reaction. AB - Cell proliferation and differentiation in multicellular organisms are partially regulated by signaling from the extracellular matrix. The ability to mimic an extracellular matrix would allow particular cell types to be specifically recognized, which is central to tissue engineering. We present a new functional DNA-based material with cell-adhesion properties. It is generated by using covalently branched DNA as primers in PCR. These primers were functionalized by click chemistry with the cyclic peptide c(RGDfK), a peptide that is known to predominantly bind to alphavbeta3 integrins, which are found on endothelial cells and fibroblasts, for example. As a covalent coating of surfaces, this DNA-based material shows cell-repellent properties in its unfunctionalized state and gains adhesiveness towards specific target cells when functionalized with c(RGDfK). These cells remain viable and can be released under mild conditions by DNase I treatment. PMID- 27410201 TI - Coming in Sportsmedicine. PMID- 27410202 TI - Editor's Notes. PMID- 27410203 TI - Letters. PMID- 27410205 TI - Scanning Sports. PMID- 27410206 TI - Abstracts at a glance. PMID- 27410207 TI - Brief Reports. PMID- 27410208 TI - Names and faces. PMID- 27410210 TI - Running Wild Achieving Arete. PMID- 27410211 TI - Editorial. PMID- 27410212 TI - A Comprehensive Preseason Fitness Evaluation for Professional Baseball Players. AB - In brief: Preseason health and fitness evaluations were performed on 40 professional baseball players to assess level of conditioning, potential for injury, and health-related lifestyle habits. Group means for coronary risk profile, muscular endurance, flexibility, and maximum aerobic capacity were normal, but screening identified many players with problems or potential problems. Test findings resulted in at least one training or life-style recommendation in every player tested. This information provides a comprehensive physiological profile of one professional baseball team. Further research is needed to define sport-specific testing for the professional baseball player. PMID- 27410213 TI - Treatment of Ankle Sprains With External Compression and Early Mobilization. AB - In brief: Edema associated with the inversion ankle sprain can be minimized by using a U- shaped compression pad held in place against the soft tissue around the fibular malleolus by an elastic wrap or tape. Control of edema allows earlier mobilization of the ankle joint, which reduces recovery time and permits the earliest possible return to sports participation. Factors to be considered in the construction of a compression pad include shaping, firmness, and conformability to the contours of the ankle and foot. Optimal results are obtained through continuous use of a U-shaped pad beneath an adjustable form of compression for as long as the potential for edema exists. PMID- 27410214 TI - External Compression for Controlling Traumatic Edema. AB - In brief: External compression is widely advocated for treating acute sports injuries. However, the rationale for using it is seldom discussed. Maintaining joint function and reducing pain and secondary hypoxic tissue death lead to more rapid and complete recovery of edema associated with sprains and strains. Poorly managed edema may contribute to the development of restricted range of motion, muscle atrophy, reduced ligament tensile strength, and joint laxity-all of which predispose an athlete to reinjury. The mechanism of action of external compression in controlling edema may be explained on the basis of its effect on capillary filtration and lymphatic drainage. PMID- 27410215 TI - Third Molars: Asset or Liability for College Athletes? AB - In brief: Many college athletes must forgo participation in competitive events because they are plagued by third molars (wisdom teeth) that do not completely erupt. The molar may remain partially impacted with a flap of gingival tissue that serves as a food trap and host for bacteria, which produce toxins that initiate an inflammatory reaction and a purulent exudate. If the exudate is trapped, the ensuing infection may spread to the buccal, sublingual, pterygomandibular, or submasseteric spaces via the fascial planes and lead to death. Treatment may include warm saline lavage with a blunted 18-gauge needle, antibiotic therapy, and analgesics. Palliative care can prevent infection or delay surgery until a more convenient time. PMID- 27410216 TI - Anterior Cruciate Ligament Injuries in Relay Tricycle Racing. AB - In brief: Each year at Indiana University in Bloomington, there is a relay in which teams of women mount and dismount specially made tricycles in a race against the clock. This paper reports on 11 cases of anterior cruciate ligament injuries in 504 participants. All of these injuries were caused by a twist or fall during the dismount from the tricycle. Seven of the 11 patients chose either arthroscopy or reconstruction of the anterior cruciate ligament. The other four patients elected a conservative approach to treatment. The authors recommend that two tricycles be used by each team to eliminate the need for a dismount. PMID- 27410217 TI - Vision, Eye Care, and the Athlete. AB - In brief: Eyesight and clarity of vision are not the only aspects of eye care for athletes. Today's eye care professionals-the opticians, ophthalmologists, and optometrists-must be able to help athletes enhance their performance not only with proper evaluation of visual acuity, but also by providing the most appropriate means of correction and protection for the sport involved. This panel of eye care experts discussed standardized testing, mandatory examinations, screening, types of eye protection for specific sports, and education needs for eye care professionals, coaches, trainers, and athletes. PMID- 27410218 TI - Body Profile of Olympic-Class Sailors. AB - In brief: This study related physiological characteristics of 30 Olympic-class sailors to their class of vessel and their coach's ranking of performance to see if there is an optimal body type. Successful competitors in general have above average height and body mass, well-developed abdominal and wrist muscles, 18% +/- 4% body fat, and a predicted aerobic power of only 45 +/- 8 ml. kg (1). min(-1) However, optimal requirements differ between categories of vessel and between skipper and crew. The authors suggest that the emphasis on heavy and moderately fat crew members with a low aerobic capacity may have adverse long-term consequences on health. They say height may provide a competitive advantage (particularly if linked to a high center of gravity), whereas mass increases frictional resistance of the vessel. But there is no strong evidence that individuals who match a perfect profile are being selected for national teams. PMID- 27410219 TI - How to Set Up a Sports Medicine Clinic. AB - Many people want to set up a sports medicine clinic but are unsure what steps to take first. And mistakes can be costly. But there are guidelines that can't be ignored and lessons to be learned from experienced entrepreneurs. PMID- 27410220 TI - Prevention and Treatment of Throwing-Arm Injuries. AB - Experts say that conditioning exercises and proper body mechanics help decrease the number of throwing-arm injuries. Once these injuries occur, the trend is toward more conservative treatment, particularly of rotator cuff injuries. PMID- 27410221 TI - Sportsmedicine Adviser. PMID- 27410223 TI - Amino acid function relates to its embedded protein microenvironment: A study on disulfide-bridged cystine. AB - In our previous study, we have shown that the microenvironments around conserved amino acids are also conserved in protein families (Bandyopadhyay and Mehler, Proteins 2008; 72:646-659). In this study, we have hypothesized that amino acids perform similar functions when embedded in a certain type of protein microenvironment. We have tested this hypothesis on the microenvironments around disulfide-bridged cysteines from high-resolution protein crystal structures. Although such cystines mainly play structural role in proteins, in certain enzymes they participate in catalysis and redox reactions. We have performed and report a functional annotation of enzymatically active cystines to their respective microenvironments. Three protein microenvironment clusters were identified: (i) buried-hydrophobic, (ii) exposed-hydrophilic, and (iii) buried hydrophilic. The buried-hydrophobic cluster encompasses a small group of 22 redox active cystines, mostly in alpha-helical conformations in a -C-x-x-C- motif from the Oxido-reductase enzyme class. All these cystines have high strain energy and near identical microenvironments. Most of the active cystines in hydrolase enzyme class belong to buried hydrophilic microenvironment cluster. In total there are 34 half-cystines detected in buried hydrophilic cluster from hydrolases, as a part of enzyme active site. Even within the buried hydrophilic cluster, there is clear separation of active half-cystines between surface exposed part of the protein and protein interior. Half-cystines toward the surface exposed region are higher in number compared to those in protein interior. Apart from cystines at the active sites of the enzymes, many more half-cystines were detected in buried hydrophilic cluster those are part of the microenvironment of enzyme active sites. However, no active half-cystines were detected in extremely hydrophilic microenvironment cluster, that is, exposed hydrophilic cluster, indicating that total exposure of cystine toward the solvent is not favored for enzymatic reactions. Although half-cystines in exposed-hydrophilic clusters occasionally stabilize enzyme active sites, as a part of their microenvironments. Analysis performed in this work revealed that cystines as a part of active sites in specific enzyme families or folds share very similar protein microenvironment regions, despite of their dissimilarity in protein sequences and position specific sequence conservations. Proteins 2016; 84:1576-1589. (c) 2016 Wiley Periodicals, Inc. PMID- 27410224 TI - Centrosymmetric resonance-assisted intermolecular hydrogen bonding chains in the enol form of beta-diketone: Crystal structure and theoretical study. AB - Isobenzofuran-1(3H)-ones (phtalides) are heterocycles that present a benzene ring fused to a gamma-lactone functionality. This structural motif is found in several natural and synthetic compounds that present relevant biological activities. In the present investigation, the 3-(2-hydroxy-4,4-dimethyl-6-oxocyclohexen-1 yl)isobenzofuran-1(3H)-one was characterized by single-crystal X-ray analysis. In the crystal structure, there are two molecules per asymmetric unit. One of them exhibits resonance assisted hydrogen bonds (RAHBs). Semi-empirical and DFT calculations were performed to obtain electronic structure and pi-delocalization parameters, in order to better understand the energy stabilization of RAHBs in the crystal packing of the studied molecule. The structural parameters showed good agreement between theoretical and experimental data. The theoretical investigation revealed that the RAHBs stabilization energy is directly related to the electronic delocalization of the enol form fragment. In addition, RAHBs significantly affected the HOMO and charge distribution around the conjugated system. PMID- 27410225 TI - Building Diatomic and Triatomic Superatom Molecules. AB - In this study, we have developed a method to create Co6Se8 superatoms in which we program the metal-ligand bonds. We exclusively form the Co6Se8 core under simple reaction conditions with a facile separation of products that contain differential substitution of the core. The combination of Co2(CO)8 and PR3 with excess Se gives the differentially and directionally substituted superatoms, Co6Se8(CO)x(PR3)(6-x). The CO groups on the superatom can be exchanged quantitatively with phosphines and isonitriles. Substitution of the CO allows us to manipulate the type and length of chemical bridge between two redox-active superatomic centers in order to modulate intersuperatomic coupling. Linking two superatoms together allows us to form the simplest superatom molecule: a diatomic molecule. We extend the superatom molecule concept to link three superatoms together in a linear arrangement to form acyclic triatomic molecules. These superatom molecules have a rich electrochemical profile and chart a clear path to a whole family of superatom molecules with new and unusual collective properties. PMID- 27410227 TI - A Physical Mechanism and Global Quantification of Breast Cancer. AB - Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN) which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2) and four regulations (HER2?TP53, CDK2?BRCA1, ATM >MDM2, TP53->ATM) were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM->MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM->MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer. PMID- 27410228 TI - Efficacy Assessment of Nucleic Acid Decontamination Reagents Used in Molecular Diagnostic Laboratories. AB - The occurrence of nucleic acid cross contamination in the laboratory resulting in false positive results of diagnostic samples is seriously problematic. Despite precautions to minimize or even avoid nucleic acid cross contaminations, it may appear anyway. Until now, no standardized strategy is available to evaluate the efficacy of commercially offered decontamination reagents. Therefore, a protocol for the reliable determination of nucleic acid decontamination efficacy using highly standardized solution and surface tests was established and validated. All tested sodium hypochlorite-based reagents proved to be highly efficient in nucleic acid decontamination even after short reaction times. For DNA Away, a sodium hydroxide-based decontamination product, dose- and time-dependent effectiveness was ascertained. For two other commercial decontamination reagents, the phosphoric acid-based DNA Remover and the non-enzymatic reagent DNA ExitusPlusTM IF, no reduction of amplifiable DNA/RNA was observed. In conclusion, a simple test procedure for evaluation of the elimination efficacy of decontamination reagents against amplifiable nucleic acid is presented. PMID- 27410229 TI - A Screen-Peck Task for Investigating Cognitive Bias in Laying Hens. AB - Affect-induced cognitive judgement biases occur in both humans and animals. Animals in a more negative affective state tend to interpret ambiguous cues more negatively than animals in a more positive state and vice versa. Investigating animals' responses to ambiguous cues can therefore be used as a proxy measure of affective state. We investigated laying hens' responses to ambiguous stimuli using a novel cognitive bias task. In the 'screen-peck' task, hens were trained to peck a high/low saturation orange circle presented on a computer screen (positive cue-P) to obtain a mealworm reward, and to not peck when the oppositely saturated orange circle was presented (negative cue-N) to avoid a one second air puff. Ambiguous cues were orange circles of intermediate saturation between the P and N cue (near-positive-NP; middle-M; near-negative-NN), and were unrewarded. Cue pecking showed a clear generalisation curve from P through NP, M, NN to N suggesting that hens were able to associate colour saturation with reward or punishment, and could discriminate between stimuli that were more or less similar to learnt cues. Across six test sessions, there was no evidence for extinction of pecking responses to ambiguous cues. We manipulated affective state by changing temperature during testing to either ~20 degrees C or ~29 degrees C in a repeated measures cross-over design. Hens have been shown to prefer temperatures in the higher range and hence we assumed that exposure to the higher temperature would induce a relatively positive affective state. Hens tested under warmer conditions were significantly more likely to peck the M probe than those tested at cooler temperatures suggesting that increased temperature in the ranges tested here may have some positive effect on hens, inducing a positive cognitive bias. PMID- 27410226 TI - Combined 3 Tesla MRI Biomarkers Improve the Differentiation between Benign vs Malignant Single Ring Enhancing Brain Masses. AB - PURPOSE: To evaluate whether the combination of imaging biomarkers obtained by means of different 3 Tesla (3T) Magnetic Resonance Imaging (MRI) advanced techniques can improve the diagnostic accuracy in the differentiation between benign and malignant single ring-enhancing brain masses. MATERIALS AND METHODS: 14 patients presenting at conventional 3T MRI single brain mass with similar appearance as regard ring enhancement, presence of peri-lesional edema and absence of hemorrhage signs were included in the study. All lesions were histologically proven: 5 pyogenic abscesses, 6 glioblastomas, and 3 metastases. MRI was performed at 3 Tesla and included Diffusion Weighted Imaging (DWI), Dynamic Susceptibility Contrast -Perfusion Weighted Imaging (DSC-PWI), Magnetic Resonance Spectroscopy (MRS), and Diffusion Tensor Imaging (DTI). Imaging biomarkers derived by those advanced techniques [Cerebral Blood Flow (CBF), relative Cerebral Blood Volume (rCBV), relative Main Transit Time (rMTT), Choline (Cho), Creatine (Cr), Succinate, N-Acetyl Aspartate (NAA), Lactate (Lac), Lipids, relative Apparent Diffusion Coefficient (rADC), and Fractional Anisotropy (FA)] were detected by two experienced neuroradiologists in joint session in 4 areas: Internal Cavity (IC), Ring Enhancement (RE), Peri-Lesional edema (PL), and Contralateral Normal Appearing White Matter (CNAWM). Significant differences between benign (n = 5) and malignant (n = 9) ring enhancing lesions were tested with Mann-Withney U test. The diagnostic accuracy of MRI biomarkers taken alone and MRI biomarkers ratios were tested with Receiver Operating Characteristic (ROC) analysis with an Area Under the Curve (AUC) >= 0.9 indicating a very good diagnostic accuracy of the variable. RESULTS: Five MRI biomarker ratios achieved excellent accuracy: IC-rADC/PL-NAA (AUC = 1), IC-rADC/IC-FA (AUC = 0.978), RE rCBV/RE-FA (AUC = 0.933), IC-rADC/RE-FA (AUC = 0.911), and IC-rADC/PL-FA (AUC = 0.911). Only IC-rADC achieved a very good diagnostic accuracy (AUC = 0.909) among MRI biomarkers taken alone. CONCLUSION: Although the major limitation of the study was the small sample size, preliminary results seem to suggest that combination of multiple 3T MRI biomarkers is a feasible approach to MRI biomarkers in order to improve diagnostic accuracy in the differentiation between benign and malignant single ring enhancing brain masses. Further studies in larger cohorts are needed to reach definitive conclusions. PMID- 27410231 TI - Surgical situation at the Turkish-Syrian border: a call for solidarity. PMID- 27410230 TI - The Fragility of Individual-Based Explanations of Social Hierarchies: A Test Using Animal Pecking Orders. AB - The standard approach in accounting for hierarchical differentiation in biology and the social sciences considers a hierarchy as a static distribution of individuals possessing differing amounts of some valued commodity, assumes that the hierarchy is generated by micro-level processes involving individuals, and attempts to reverse engineer the processes that produced the hierarchy. However, sufficient experimental and analytical results are available to evaluate this standard approach in the case of animal dominance hierarchies (pecking orders). Our evaluation using evidence from hierarchy formation in small groups of both hens and cichlid fish reveals significant deficiencies in the three tenets of the standard approach in accounting for the organization of dominance hierarchies. In consequence, we suggest that a new approach is needed to explain the organization of pecking orders and, very possibly, by implication, for other kinds of social hierarchies. We develop an example of such an approach that considers dominance hierarchies to be dynamic networks, uses dynamic sequences of interaction (dynamic network motifs) to explain the organization of dominance hierarchies, and derives these dynamic sequences directly from observation of hierarchy formation. We test this dynamical explanation using computer simulation and find a good fit with actual dynamics of hierarchy formation in small groups of hens. We hypothesize that the same dynamic sequences are used in small groups of many other animal species forming pecking orders, and we discuss the data required to evaluate our hypothesis. Finally, we briefly consider how our dynamic approach may be generalized to other kinds of social hierarchies using the example of the distribution of empty gastropod (snail) shells occupied in populations of hermit crabs. PMID- 27410232 TI - Clinical Value of (18)F-FDG- PET-CT in the Preoperative Staging of Peritoneal Carcinomatosis from Colorectal Origin. AB - BACKGROUND: Adequate staging is essential in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) who are candidates for cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Metabolic imaging using (18)F-FDG-PET-CT is commonly used to exclude distant metastasis in these patients. Here, we aimed to assess the performance of (18)F-FDG-PET-CT in locoregional staging of the extent of PC. METHODS: Patients with PC from CRC underwent staging including (18)F-FDG-PET-CT. In the absence of systemic dissemination, CRS and oxaliplatin based HIPEC were performed. The extent of PC was quantified during surgery using the modified 7 region count (7RC). The correlation between imaging based estimation of PC extent and surgical 7RC was analyzed using Pearson correlation using both patient based and region based analyses. RESULTS: Fifty-five patients were included between February 2005 and October 2018. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 57%, 98%, 95%, 78% and 82% respectively for non-mucinous tumors and 32%, 100%, 100%, 55% and 63% respectively. 18F-FDG-PET-CT detected the presence of colorectal PC in 96% of patients suffering from PC with nonmucinous histology and in 60% of patients suffering from PC with mucinous histology. Correlation between imaging 7RC and surgical 7RC was better for PC with nonmucinous histology (r = 0.623) than for PC with mucinous histology (r = 0.180). CONCLUSIONS: Despite of underestimating the exact extent of disease involvement, 18F-FDG-PET-CT shows good performance in detecting colorectal PC with nonmucinous histology. For colorectal PC with mucinous histology, 18F-FDG- PET-CT, however, shows poor performance. Since 18F-FDG-PET-CT did not detect the presence of colorectal PC in all patients in whom long-term survival could be achieved, 18F-FDG-PET-CT should be implemented into a broad preoperative assessment strategy. PMID- 27410233 TI - Modeling Costs and Impacts of Introducing Early Infant Male Circumcision for Long Term Sustainability of the Voluntary Medical Male Circumcision Program. AB - Voluntary medical male circumcision (VMMC) has been shown to be an effective prevention strategy against HIV infection in males [1-3]. Since 2007, the President's Emergency Plan for AIDS Relief (PEPFAR) has supported VMMC programs in 14 priority countries in Africa. Today several of these countries are preparing to transition their VMMC programs from a scale-up and expansion phase to a maintenance phase. As they do so, they must consider the best approaches to sustain high levels of male circumcision in the population. The two alternatives under consideration are circumcising adolescents 10-14 years old over the long term or integrating early infant male circumcision (EIMC) into maternal and child health programs. The paper presents an analysis, using the Decision Makers Program Planning Tool, Version 2.0 (DMPPT 2.0), of the estimated cost and impact of introducing EIMC into existing VMMC programs in several countries in eastern and southern Africa. Limited cost data exist for the implementation of EIMC, but preliminary studies, such as the one detailed in Mangenah, et al. [4-5], suggest that the cost of EIMC may be less than that of adolescent and adult male circumcision. If this is the case, then adding EIMC to the VMMC program will increase the number of circumcisions that need to be performed but will not increase the total cost of the program over the long term. In addition, we found that a delayed or slow start-up of EIMC would not substantially reduce the impact of adding it to the program or increase cumulative long-term costs, which should make introduction of EIMC more feasible and attractive to countries contemplating such a program innovation. PMID- 27410234 TI - Modeling the Impact of Uganda's Safe Male Circumcision Program: Implications for Age and Regional Targeting. AB - BACKGROUND: Uganda aims to provide safe male circumcision (SMC) to 80% of men ages 15-49 by 2016. To date, only 2 million men have received SMC of the 4.2 million men required. In response to age and regional trends in SMC uptake, the country sought to re-examine its targets with respect to age and subnational region, to assess the program's progress, and to refine the implementation approach. METHODS AND FINDINGS: The Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0), was used in conjunction with incidence projections from the Spectrum/AIDS Impact Module (AIM) to conduct this analysis. Population, births, deaths, and HIV incidence and prevalence were used to populate the model. Baseline male circumcision prevalence was derived from the 2011 AIDS Indicator Survey. Uganda can achieve the most immediate impact on HIV incidence by circumcising men ages 20-34. This group will also require the fewest circumcisions for each HIV infection averted. Focusing on men ages 10-19 will offer the greatest impact over a 15-year period, while focusing on men ages 15-34 offers the most cost-effective strategy over the same period. A regional analysis showed little variation in cost-effectiveness of scaling up SMC across eight regions. Scale-up is cost-saving in all regions. There is geographic variability in program progress, highlighting two regions with low baseline rates of circumcision where additional efforts will be needed. CONCLUSION: Focusing SMC efforts on specific age groups and regions may help to accelerate Uganda's SMC program progress. Policy makers in Uganda have already used model outputs in planning efforts, proposing males ages 10-34 as a priority group for SMC in the 2014 application to the Global Fund's new funding model. As scale-up continues, the country should also consider a greater effort to expand SMC in regions with low MC prevalence. PMID- 27410235 TI - Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle. AB - Evidence indicates that central galanin is involved in regulation of insulin resistance in animals. This study investigates whether type 1 galanin receptor (GAL1) in the brain mediates the ameliorative effect of galanin on insulin resistance in skeletal muscles of type 2 diabetic rats. Rats were intracerebroventricularly (i.c.v.) injected with galanin(1-13)-bradykinin(2-9) amide (M617), a GAL1 agonist, and/or Akti-1/2, an Akt inhibitor, via caudal veins once per day for 10 days. Insulin resistance in muscle tissues was evaluated by glucose tolerance and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2 deoxyglucose (2-NBDG) tests, peroxisome proliferator-activated receptor-gamma (PPARgamma), glucose transporter 4 (GLUT4) mRNA expression levels, Akt phosphorylation, and GLUT4 and vesicle-associated membrane protein 2 (VAMP2) concentration at plasma membranes in muscle cells. The results show that i.c.v. treatment with M617 increased glucose tolerance, 2-NBDG uptake, PPARgamma levels, Akt phosphorylation, GLUT4 protein, and GLUT4 mRNA expression levels as well as GLUT4 and VAMP2 concentration at plasma membranes. All increases may be blocked by pretreatment with Akti-1/2. These results suggest that activated central GAL1 may trigger the Akt signaling pathway to alleviate insulin resistance in muscle cells. Therefore, the impact of galanin on insulin resistance is mediated mainly by GAL1 in the brain, and the GAL1 agonist may be taken as a potential antidiabetic agent for treatment of type 2 diabetes mellitus. (c) 2016 Wiley Periodicals, Inc. PMID- 27410237 TI - Racial Disparities in End-of-Life Issues in Patients with Chronic Kidney Disease. PMID- 27410238 TI - The pathway to clinical use of a cancer biomarker. AB - Biomarkers play a key role in the diagnosis and management of patients with cancer, and are important for fulfilling the promise of precision medicine in oncology. However, although numerous biomarkers have been shown to have clinical validity, many have not undergone rigorous testing to demonstrate clinical utility so that they can be appropriately incorporated into clinical care. This review article highlights the characteristics of a good biomarker and the steps required to demonstrate clinical utility, and gives examples of both successful established biomarkers and promising new tissue-based and circulating biomarkers on the horizon. PMID- 27410239 TI - Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990-2015. AB - BACKGROUND: In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States. OBJECTIVE: To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. METHODS: We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990-July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening illness), and those suggesting anaphylaxis and Guillain-Barre syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV. RESULTS: VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination. CONCLUSIONS: This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre licensure studies. PMID- 27410240 TI - Best practice for analysis of shared clinical trial data. AB - BACKGROUND: Greater transparency, including sharing of patient-level data for further research, is an increasingly important topic for organisations who sponsor, fund and conduct clinical trials. This is a major paradigm shift with the aim of maximising the value of patient-level data from clinical trials for the benefit of future patients and society. We consider the analysis of shared clinical trial data in three broad categories: (1) reanalysis - further investigation of the efficacy and safety of the randomized intervention, (2) meta analysis, and (3) supplemental analysis for a research question that is not directly assessing the randomized intervention. DISCUSSION: In order to support appropriate interpretation and limit the risk of misleading findings, analysis of shared clinical trial data should have a pre-specified analysis plan. However, it is not generally possible to limit bias and control multiplicity to the extent that is possible in the original trial design, conduct and analysis, and this should be acknowledged and taken into account when interpreting results. We highlight a number of areas where specific considerations arise in planning, conducting, interpreting and reporting analyses of shared clinical trial data. A key issue is that that these analyses essentially share many of the limitations of any post hoc analyses beyond the original specified analyses. The use of individual patient data in meta-analysis can provide increased precision and reduce bias. Supplemental analyses are subject to many of the same issues that arise in broader epidemiological analyses. Specific discussion topics are addressed within each of these areas. Increased provision of patient-level data from industry and academic-led clinical trials for secondary research can benefit future patients and society. Responsible data sharing, including transparency of the research objectives, analysis plans and of the results will support appropriate interpretation and help to address the risk of misleading results and avoid unfounded health scares. PMID- 27410241 TI - Population Normative Data for the CERAD Word List and Victoria Stroop Test in Younger- and Middle-Aged Adults: Cross-Sectional Analyses from the Framingham Heart Study. AB - BACKGROUND/STUDY CONTEXT: To provide baseline normative data on tests of verbal memory and executive function for nondemented younger- and middle-aged adults. METHODS: The Consortium to Establish a Registry for Alzheimer's Disease word list memory task (CERAD-WL) and Victoria Stroop Test (VST) were administered to 3362 Framingham Heart Study (FHS) volunteer participants aged 24-78 years. Analyses of the effects of age, gender, and education were conducted. Normative data on traditional measures and error responses are reported for each test. RESULTS: Traditional measures were significantly associated with both age and education in this cohort. Error responses also evidenced significant age and education effects. CONCLUSION: These data provide a normative comparison for assessment of verbal memory and executive functioning capabilities in younger- and middle-aged adults and may be utilized as a tool for preclinical studies of disease in this population. PMID- 27410242 TI - Aging, Functional Learning, and Inhibition. AB - BACKGROUND/STUDY CONTEXT: The study compared the learning performance of younger and older adults in situations differing in the number of cues that could be relied on for predicting the value of a criterion. Two hypotheses were tested: one based on the assumption that the greater the inhibition effort needed in the task, the greater the difference between younger and older participants, and the other based on the fact that the context in which inhibition occurs plays a role, and consequently that the level of difficulty of the four learning conditions can be better predicted from the number of possible sets of valid cues. METHODS: A total of 240 adults (18-90 years old) had to learn to predict the amount of drink delivered by a drink dispenser on the basis of four cues (the height of four vertical bars). The participants were randomly distributed between four experimental conditions, one valid cue, two valid cues, three valid cues, and all valid cues. The measures that were calculated for each participant under each condition included the squared mean differences between judgment and criterion as an index of performance, and cue utilizations as a test of both the learning of the strength of direct linear relationships and of inhibition. RESULTS: The results validated the hypothesis that the level of difficulty of the four learning conditions can be better predicted from the number of possible sets of valid cues. In all conditions and in each age group, cue utilizations were direct in the first block with no feedback. Older adults discounted the nonpertinent cues as well as younger adults, whereas participants aged over 76 only succeeded under the least demanding conditions. The presence of nonpertinent cues affected the learning of direct cues, even among the younger participants. CONCLUSION: This study shows that older adults' ability to detect (and use) valid cues in an environment that contains both valid and invalid cues is relatively well preserved. It also shows that the mere presence of invalid cues can affect the learning of direct cues, which constitutes a new result in functional learning. Future research conducted in cognitive aging should examine the role of invalid cues in functional learning. PMID- 27410243 TI - Exploring the Cognitive Processes Causing the Age-Related Categorization Deficit in the Recognition of Facial Expressions. AB - BACKGROUND/STUDY CONTEXT: Elderly people do not categorize emotional facial expressions as accurately as younger people, particularly negative emotions. Although age-related impairments in decoding emotions in facial expressions are well documented, the causes of this deficit are poorly understood. This study examined the potential mechanisms that account for this age-related categorization deficit by assessing its dependence on presentation time. METHODS: Thirty young (19-27 years old) and 31 older (68-78 years old) Chinese adults were asked to categorize the six basic emotions in facial expressions, each presented for 120, 200, 600, or 1000 ms, before and after exposure to a neutral facial expression. RESULTS: Shortened presentation times caused an age-related deficit in the recognition of happy faces, whereas no deficit was observed at longer exposure times. An age-related deficit was observed for all negative emotions but was not exacerbated by shorter presentation times. CONCLUSION: Age-related deficits in categorization of positive and negative emotions are caused by different mechanisms. Because negative emotions are perceptually similar, they cause high categorization demands. Elderly people may need more evidence in favor of the target emotion than younger people, and they make mistakes if this surplus of evidence is missing. In contrast, perceptually distinct happy faces were easily identified, and elderly people only failed when the presentation time was too short for their slower perceptual processing. PMID- 27410244 TI - The Effect of Prior Task Success on Older Adults' Memory Performance: Examining the Influence of Different Types of Task Success. AB - BACKGROUND/STUDY CONTEXT: Negative aging stereotypes can lead older adults to perform poorly on memory tests. Yet, memory performance can be improved if older adults have a single successful experience on a cognitive test prior to participating in a memory experiment (Geraci & Miller, 2013, Psychology and Aging, 28, 340-345). The current study examined the effects of different types of prior task experience on subsequent memory performance. METHODS: Before participating in a verbal free recall experiment, older adults in Experiment 1 successfully completed either a verbal or a visual cognitive task or no task. In Experiment 2, they successfully completed either a motor task or no task before participating in the free recall experiment. RESULTS: Results from Experiment 1 showed that relative to control (no prior task), participants who had prior success, either on a verbal or a visual task, had better subsequent recall performance. Experiment 2 showed that prior success on a motor task, however, did not lead to a later memory advantage relative to control. CONCLUSION: These findings demonstrate that older adults' memory can be improved by a successful prior task experience so long as that experience is in a cognitive domain. PMID- 27410245 TI - The Effect of Pressure Ulcers on the Survival in Patients With Advanced Dementia and Comorbidities. AB - BACKGROUND/STUDY CONTEXT: The mortality rates for many leading causes of death have declined over the past decade. Advanced dementia with comorbidities has steadily increased to become one of the leading causes of death in the elderly population. Therefore, this study examined the effect of pressure ulcers on the survival time of patients with advanced dementia and comorbidities. METHODS: Data were reviewed from all the files of 147 patients hospitalized over a period of 31/2 years. Ninety-nine tube-fed patients suffering from advanced dementia were assessed; 72 (66.5%) had pressure ulcers and 27 (33.5%) were without pressure ulcers at admission. Logistic regression analysis was used to estimate the odds ratio and 95% confidence intervals for pressure ulcers group versus non-pressure ulcers group. Unadjusted Cox model and Cox proportional hazards model were used to assess the hazard ratio for pressure ulcers and the association between pressure ulcers and survival time, respectively. Kaplan-Meier model was used to visually confirm the existence of proportional hazards of pressure ulcers on survival. RESULTS: The median survival of advanced dementia patients with pressure ulcers was significantly shorter, compared with those without pressure ulcers (96 vs. 863 days). Significant lower hemoglobin and serum albumin levels were found in the patients with pressure ulcers. CONCLUSION: Advance dementia and pressure ulcers in the same patient results in earlier mortality. Advanced dementia patients with pressure ulcers had significantly lower survival expectancy in comparison with similar patients without pressure ulcers. Clinical and ethical implications are discussed. PMID- 27410246 TI - Age-Related Changes in Attentional Control Using an N-Back Working Memory Paradigm. AB - BACKGROUND/STUDY CONTEXT: Older adults tend to be affected by task-irrelevant distracters. However, whether or not this aging effect is evident when task irrelevant and relevant stimuli are presented across different sensory modalities is still a subject of debate. The purpose of the present study was to clarify age related differences in the effects of auditory distraction on visual information processing. METHODS: Participants included 20 young individuals, 20 younger-old individuals in their 60s, and 20 older-old individuals in their 70s. Visual n back (1-back, 2-back) working memory (WM) tasks using Japanese words were examined with and without auditory distracter conditions. Participants' performances were analyzed using a three-way analysis of variance: 3 (age group) * 2 (distraction) * 2 (working memory load). RESULTS: The effects of auditory distractions were influenced by aging and WM load. Auditory distractions disturbed WM performances preferentially in older adults. Further, participants in the older-old group were more affected by auditory distractions than those in the younger-old group, especially during the 2-back task. CONCLUSION: These results suggested that the WM performances for visual n-back tasks were largely disturbed by auditory distractions in older adults but not in young adults. PMID- 27410247 TI - Combining pseudo dinucleotide composition with the Z curve method to improve the accuracy of predicting DNA elements: a case study in recombination spots. AB - Pseudo dinucleotide composition (PseDNC) and Z curve showed excellent performance in the classification issues of nucleotide sequences in bioinformatics. Inspired by the principle of Z curve theory, we improved PseDNC to give the phase-specific PseDNC (psPseDNC). In this study, we used the prediction of recombination spots as a case to illustrate the capability of psPseDNC and also PseDNC fused with Z curve theory based on a novel machine learning method named large margin distribution machine (LDM). We verified that combining the two widely used approaches could generate better performance compared to only using PseDNC with a support vector machine based (SVM-based) model. The best Mathew's correlation coefficient (MCC) achieved by our LDM-based model was 0.7037 through the rigorous jackknife test and improved by ~6.6%, ~3.2%, and ~2.4% compared with three previous studies. Similarly, the accuracy was improved by 3.2% compared with our previous iRSpot-PseDNC web server through an independent data test. These results demonstrate that the joint use of PseDNC and Z curve enhances performance and can extract more information from a biological sequence. To facilitate research in this area, we constructed a user-friendly web server for predicting hot/cold spots, HcsPredictor, which can be freely accessed from . In summary, we provided a united algorithm by integrating Z curve with PseDNC. We hope this united algorithm could be extended to other classification issues in DNA elements. PMID- 27410248 TI - The Synthesis of trans-Flavan-3-ol Gallates by Regioselective Oxidative Etherification and Their Cytotoxicity Mediated by 67 LR. AB - We report on a chiral pool approach for the synthesis of trans-flavan-3-ol gallates from epichlorohydrin. The trans-flavan-3-ol gallates were prepared by the cycloetherification of the phenol at the C2 benzylic position of 2-acylozyl 1,3-diarylpropane during regioselective C-H oxidation. The 1,3-diarylpropanes were prepared starting from epichlorohydrin by epoxide opening with A and B ring precursors, followed by acylation of the resultant alcohol with galloyl chloride. The availability of both the enantiomers of epichlorohydrin allowed the preparation of the corresponding enantiomer using the same procedure. The cytotoxicity of the compounds against U266 cells was tested, in which 5-deoxy 7,3'-O-dimethyl gallocatechin gallate exhibited cytotoxicity that was more than ten times stronger than natural (-)-EGCG. In addition, the absolute configuration of the derivatives did not critically affect the biological activity. PMID- 27410249 TI - Heart aging measured with coronary artery calcium scoring and cardiovascular risk assessment algorithms in HIV infected patients. AB - ABTRACT Many sources have highlighted the high incidence of premature cardiovascular events in HIV infected patients. This raises the suspicion of an accelerated aging of the vascular system in this disease characterized by chronic systemic subliminal inflammation and immune dysregulation. Unfortunately all currently available risk assessment algorithms based on traditional risk factors, and even those containing more HIV-specific factors, fail to accurately predict risk in a large proportion of patients. In the general population several models have implemented imaging data to refine risk assessment, and the concept of vascular aging has been of value in improving the performance of these algorithms. It is expected that HIV patients may benefit from a similar approach as it becomes clearer that vascular imaging provides valuable prognostic information in this patient category. PMID- 27410250 TI - Stigma and disease disclosure among HIV+ individuals: the moderating role of emotion dysregulation. AB - Increased disclosure of HIV status has been shown to reduce disease transmission among persons living with HIV (PLHIV). HIV-related stigma has been shown to reduce HIV disclosure; however, little is known about factors that may underlie the relation between HIV-related stigma and HIV disclosure. The current study examined emotion dysregulation (i.e., maladaptive generation, processing, and modulation of one's emotions) in the relation between HIV-related stigma, sub facets of HIV-related stigma, and HIV disclosure among PLHIV seeking psychological treatment (n = 80; 61.3% male; 56.3% African-American (non Hispanic); Mage = 48.25, SD = 7.39). Results indicated past experiences of rejection due to one's HIV status (i.e., enacted stigma), as well as subjective beliefs regarding how PLHIV are evaluated by others (i.e., public attitudes stigma), are significantly related to HIV disclosure. Additionally, these relations are moderated by emotion dysregulation. Specifically, greater HIV related stigma is associated with reduced HIV disclosure for individuals with greater emotion dysregulation. However, emotion dysregulation did not moderate the relations between negative self-image (e.g., shame, guilt) or disclosure concerns and HIV disclosure. Findings suggest emotion dysregulation may play a moderating role for certain types of HIV disclosure. PMID- 27410251 TI - Mother-Infant Emotion Regulation at Three Months: The Role of Maternal Anxiety, Depression and Parenting Stress. AB - BACKGROUND: While the association between anxiety and postpartum depression is well known, few studies have investigated the relationship between these two states and parenting stress. Furthermore, a number of studies have found that postpartum depression affects mother-infant emotion regulation, but there has been only one study on anxiety and emotion regulation and no studies at all on parenting stress and emotion regulation. Therefore, the primary aim of our study is to identify, in a community sample of 71 mothers, the relationship between maternal depression, anxiety, and parenting stress. The second aim is to examine the relationship between anxiety, postpartum depression, and parenting stress and mother-infant emotion regulation assessed at 3 months. METHODS: Mother-infant interaction was coded with a modified version of the Infant Caregiver and Engagement Phases (ICEP) using a microanalytic approach. The Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), and Parenting Stress Index-Short Form (PSI-SF) were administered to the mothers to assess depression, anxiety, and parenting stress, respectively. RESULTS: Analysis revealed correlations between anxiety and depression, showing that parenting stress is associated with both states. In a laboratory observation, depression was correlated with both negative maternal states and negative dyadic matches as well as infant positive/mother negative mismatches; anxiety was correlated with both negative maternal states and infant negative states as well as mismatches involving one of the partners having a negative state. Multiple regression analysis showed that anxiety is a greater predictor than depression of less adequate styles of mother-infant emotion regulation. Parenting stress was not shown to predict such regulation. PMID- 27410252 TI - Efficient monitoring of protein ubiquitylation levels using TUBEs-based microarrays. AB - Analyzing protein ubiquitylation changes during physiological or pathological processes is challenging due to its high reversibility and dynamic turnover of modified targets. We have developed a protein microarray to assess endogenous ubiquitylation levels from cell cultures, employing tandem ubiquitin-binding entities (TUBEs) with three or four ubiquitin-associated (UBA) domains as capture probes. Adriamycin (ADR)-stimulated MCF7 cells were used to differentiate protein ubiquitylation levels between cells that are sensitive or resistant to ADR treatment. We show that TUBEs-based microarrays can be used for the analysis of cellular processes regulated by ubiquitylation and for the detection of pathologies with aberrant ubiquitylation levels. PMID- 27410253 TI - E-cigarettes and the need and opportunities for alternatives to animal testing. AB - E-cigarettes have become within only one decade an important commodity, changing the market of the most mass-killing commercial product. While a few years ago estimates suggested that in the course of the 21st century one billion people would die prematurely from tobacco consumption, e-cigarettes continuously gaining popularity promise 10-30fold lower health effects, possibly strongly changing this equation. However, they still are not a harmless life-style drug. Acceptability simply depends on whether we compare their use to smoking or to not smoking. In the absence of long-term follow-up health data of users, additional uncertainty comes from the lack of safety data, though this uncertainty likely only is whether they represent 3 or 10% of the risk of their combustible counterpart. This means that there is little doubt that they represent a prime opportunity for smokers to switch, but also that their use by non-smokers should be avoided where possible. The real safety concerns, however, are that e cigarettes expose their users to many compounds, contaminants and especially flavors (more than 7,000 according to recent counts), which have mostly not been tested, especially not for long-term inhalation exposure. Neither the precautionary traditional animal testing nor post-marketing surveillance will offer us data of sufficient quality or sufficiently fast to support product development and regulatory decisions. Thus, alternative methods lend themselves to fill this gap, making this new product category a possible engine for new method development and its implementation and validation. PMID- 27410254 TI - Blood collection by gingival puncture on hamsters reduces animal number in leptospirosis virulence tests. PMID- 27410255 TI - Two Good Read-across Practice workshops. Making it work for you! PMID- 27410256 TI - ERRATUM. AB - [This corrects the article DOI: 10.1016/S0377-1237(09)80047-6.]. PMID- 27410257 TI - A self-protection phenomenon in the Nafion membrane when it breathes in methanol saturated air. AB - Ex situ characterizations based on TGA and XRD techniques revealed that MeOH vapor had little influence on the Nafion microstructures. To reveal the underlying mechanism, in this study, we designed new FTIR-based equipment to track in situ the microstructural changes of a bulk Nafion membrane in MeOH saturated air. First, an interesting MeOH-breathing phenomenon was found in the ionic domains of Nafion. It demonstrated that there existed a dynamic equilibrium between the sorption and desorption processes of MeOH vapor in Nafion. Second, the FTIR results also detected the high stability of the hydrophobic regions of Nafion in MeOH vapor. The super-acid -CF2-SO3H always retained a small quantity of bonded H2O (H(+)(H2O)n) inside the Nafion membrane. MeOH vapor was absorbed first into the hydrophilic regions, however, the interactions between -CF2-SO3H and MeOH vapor were much weaker than those between -CF2-SO3H and H(+)(H2O)n. Therefore, a protective layer composed of residual water formed in the lumen of the hydrophilic ionic domains of Nafion, which protected its hydrophobic regions from the MeOH attack. Hereby, the self-protection ability of Nafion in MeOH vapor was detected for the first time. This work gave a new insight into the complex interplay between Nafion and MeOH vapor. PMID- 27410258 TI - South (S)- and North (N)-Methanocarba-7-Deazaadenosine Analogues as Inhibitors of Human Adenosine Kinase. AB - Adenosine kinase (AdK) inhibitors raise endogenous adenosine levels, particularly in disease states, and have potential for treatment of seizures, neurodegeneration, and inflammation. On the basis of the South (S) ribose conformation and molecular dynamics (MD) analysis of nucleoside inhibitors bound in AdK X-ray crystallographic structures, (S)- and North (N)-methanocarba (bicyclo[3.1.0]hexane) derivatives of known inhibitors were prepared and compared as human (h) AdK inhibitors. 5'-Hydroxy (34, MRS4202 (S); 55, MRS4380 (N)) and 5' deoxy 38a (MRS4203 (S)) analogues, containing 7- and N(6)-NH phenyl groups in 7 deazaadenine, robustly inhibited AdK activity (IC50 ~ 100 nM), while the 5' hydroxy derivative 30 lacking the phenyl substituents was weak. Docking in the hAdK X-ray structure and MD simulation suggested a mode of binding similar to 5' deoxy-5-iodotubercidin and other known inhibitors. Thus, a structure-based design approach for further potency enhancement is possible. The potent AdK inhibitors in this study are ready to be further tested in animal models of epilepsy. PMID- 27410259 TI - Advance Care Planning in Dementia: Do Family Carers Know the Treatment Preferences of People with Early Dementia? AB - BACKGROUND AND AIMS: When a person with dementia (PWD) has lost the ability to make treatment decisions, clinicians often rely on family carers to know and articulate these preferences with assumed accuracy. This study used the Life Support Preferences Questionnaire (LSPQ) to explore whether family carers' choices show agreement with the end of life care preferences of the person with dementia for whom they care and what factors influence this. METHODS: A cross sectional study interviewing 60 dyads (a person with early dementia and preserved capacity and their family carer) each completing a modified LSPQ. We assessed how closely carers' choices resembled the PWD's preferences for treatment in three proposed health states: the here and now; severe stroke with coma; terminal cancer. Agreement between the PWD and their family carer responses was assessed using Kappa and Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) statistics. We examined whether carer burden and distress, and relationship quality, influenced agreement. RESULTS: In interviews PWD were able to indicate their treatment preferences across all three scenarios. In the here-and-now most wanted antibiotics (98%), fewer cardio-pulmonary resuscitation (CPR) (50%) and tube feeding (47%). In severe stroke and coma antibiotics remained the more preferred treatment (88%), followed by CPR (57%) and tube feeding (30%). In advanced cancer PWD expressed lower preferences for all treatments (antibiotics 68%; CPR 50%; tube feeding 37%). Carers' choices were similar to the PWDs' preferences in the here-and-now (71% (k = 0.03; PABAK = 0.4) with less agreement for future hypothetical health states. In severe stroke and coma carers tended wrongly to suggest that the PWD preferred more intervention (antibiotic, 67%; k = -0.022; PABAK = -0.60; CPR, 73%; k = 0.20; PABAK = -0.20, tube feeding, 66%; k = 0.25; PABAK = -0.12). In advanced cancer the agreement between PWD and carers was low (antibiotics; k = -0.03; PABAK = -0.52; CPR, k = -0.07; PABAK = -0.45; tube feeding; k = 0.20; PABAK = -0.22). However, both PWD and carers showed marked uncertainty about their preferences for end of life treatment choices. Relationship quality, carer distress and burden had no influence on agreement. CONCLUSIONS: This study is the first to have used the LSPQ with PWD in the UK to consider treatment options in hypothetical illness scenarios. Key finding are that family carers had a low to moderate agreement with PWD on preferences for end of life treatment. This underscores how planning for care at the end of life is beset with uncertainty, even when the carer and PWD perceive the care giving/receiving relationship is good. Families affected by dementia may benefit from early and ongoing practical and emotional support to prepare for potential changes and aid decision making in the context of the realities of care towards the end of life. PMID- 27410260 TI - Strategies for the release of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in an enzymatic hydrolyzate of alpha-lactalbumin. AB - Bovine alpha-lactalbumin (alpha-La) contains numerous dipeptidyl peptidase IV (DPP-IV) inhibitory peptide sequences within its primary structure. In silico analysis indicated that the targeted hydrolysis of alpha-La with elastase should release DPP-IV inhibitory peptides. An alpha-La isolate was hydrolysed with elastase under different conditions using an experimental design approach incorporating 3 factors (temperature, pH and enzyme to substrate ratio (E : S) ratio) at 2 levels. The hydrolyzate generated at pH 8.5, 50 degrees C, E : S 2.0% (w/w) (H9) displayed the highest mean DPP-IV inhibition value at 3.1 mg mL( 1) of 75.8 +/- 3.7% and had a half maximal DPP-IV inhibitory concentration (IC50) value of 1.20 +/- 0.12 mg mL(-1). Five alpha-La-derived DPP-IV inhibitory peptides (GY, GL, GI, NY and WL) predicted to be released in silico were identified by liquid-chromatography tandem mass spectrometry (LC-MS/MS) within H9 and its simulated gastrointestinal digestion (SGID) sample. This preliminary study demonstrated the benefit of using a targeted approach combined with an experimental design in the generation of dietary protein hydrolyzates with DPP-IV inhibitory properties. PMID- 27410261 TI - Indicator Properties of Baltic Zooplankton for Classification of Environmental Status within Marine Strategy Framework Directive. AB - The European Marine Strategy Framework Directive requires the EU Member States to estimate the level of anthropogenic impacts on their marine systems using 11 Descriptors. Assessing food web response to altered habitats is addressed by Descriptor 4 and its indicators, which are being developed for regional seas. However, the development of simple foodweb indicators able to assess the health of ecologically diverse, spatially variable and complex interactions is challenging. Zooplankton is a key element in marine foodwebs and thus comprise an important part of overall ecosystem health. Here, we review work on zooplankton indicator development using long-term data sets across the Baltic Sea and report the main findings. A suite of zooplankton community metrics were evaluated as putative ecological indicators that track community state in relation to Good Environmental Status (GES) criteria with regard to eutrophication and fish feeding conditions in the Baltic Sea. On the basis of an operational definition of GES, we propose mean body mass of zooplankton in the community in combination with zooplankton stock measured as either abundance or biomass to be applicable as an integrated indicator that could be used within the Descriptor 4 in the Baltic Sea. These metrics performed best in predicting zooplankton being in-GES when considering all datasets evaluated. However, some other metrics, such as copepod biomass, the contribution of copepods to the total zooplankton biomass or biomass-based Cladocera: Copepoda ratio, were equally reliable or even superior in certain basin-specific assessments. Our evaluation suggests that in several basins of the Baltic Sea, zooplankton communities currently appear to be out-of GES, being comprised by smaller zooplankters and having lower total abundance or biomass compared to the communities during the reference conditions; however, the changes in the taxonomic structure underlying these trends vary widely across the sea basins due to the estuarine character of the Baltic Sea. PMID- 27410262 TI - Women 1.5 Times More Likely to Leave STEM Pipeline after Calculus Compared to Men: Lack of Mathematical Confidence a Potential Culprit. AB - The substantial gender gap in the science, technology, engineering, and mathematics (STEM) workforce can be traced back to the underrepresentation of women at various milestones in the career pathway. Calculus is a necessary step in this pathway and has been shown to often dissuade people from pursuing STEM fields. We examine the characteristics of students who begin college interested in STEM and either persist or switch out of the calculus sequence after taking Calculus I, and hence either continue to pursue a STEM major or are dissuaded from STEM disciplines. The data come from a unique, national survey focused on mainstream college calculus. Our analyses show that, while controlling for academic preparedness, career intentions, and instruction, the odds of a woman being dissuaded from continuing in calculus is 1.5 times greater than that for a man. Furthermore, women report they do not understand the course material well enough to continue significantly more often than men. When comparing women and men with above-average mathematical abilities and preparedness, we find women start and end the term with significantly lower mathematical confidence than men. This suggests a lack of mathematical confidence, rather than a lack of mathematically ability, may be responsible for the high departure rate of women. While it would be ideal to increase interest and participation of women in STEM at all stages of their careers, our findings indicate that if women persisted in STEM at the same rate as men starting in Calculus I, the number of women entering the STEM workforce would increase by 75%. PMID- 27410263 TI - Resolving Discrepant Findings on ANGPTL8 in beta-Cell Proliferation: A Collaborative Approach to Resolving the Betatrophin Controversy. AB - The beta-cell mitogenic effects of ANGPTL8 have been subjected to substantial debate. The original findings suggested that ANGPTL8 overexpression in mice induced a 17-fold increase in beta-cell proliferation. Subsequent studies in mice contested this claim, but a more recent report in rats supported the original observations. These conflicting results might be explained by variable ANGPTL8 expression and differing methods of beta-cell quantification. To resolve the controversy, three independent labs collaborated on a blinded study to test the effects of ANGPTL8 upon beta-cell proliferation. Recombinant human betatrophin (hBT) fused to maltose binding protein (MBP) was delivered to mice by intravenous injection. The results demonstrate that ANGPTL8 does not stimulate significant beta-cell proliferation. Each lab employed different methods for beta-cell identification, resulting in variable quantification of beta-cell proliferation and suggests a need for standardizing practices for beta-cell quantification. We also observed a new action of ANGPTL8 in stimulating CD45+ hematopoietic-derived cell proliferation which may explain, in part, published discrepancies. Overall, the hypothesis that ANGPTL8 induces dramatic and specific beta-cell proliferation can no longer be supported. However, while ANGPTL8 does not stimulate robust beta cell proliferation, the original experimental model using drug-induced (S961) insulin resistance was validated in subsequent studies, and thus still represents a robust system for studying signals that are either necessary or sufficient for beta-cell expansion. As an added note, we would like to commend collaborative group efforts, with repetition of results and procedures in multiple laboratories, as an effective method to resolve discrepancies in the literature. PMID- 27410264 TI - Chemical Synthesis of Glycosaminoglycans. AB - Glycosaminoglycans (GAGs) as one major part of the glycocalyx are involved in many essential biological cell processes, as well as in many courses of diseases. Because of the potential therapeutic application of GAG polymers, fragments, and also derivatives toward different diseases (e.g., heparin derivatives against Alzheimer's disease), there is a continual growing demand for new chemical syntheses, which suffice the high claim to stereoselectivity and chemoselectivity. This Review summarizes the progress of chemical syntheses of GAGs over the last 10 years. For each class of the glycosaminoglycans-hyaluronan (HA), heparan sulfate/heparin (HS/HP), chondroitin/dermatan sulfate (CS/DS), and keratan sulfate (KS)-mainly novel glycosylation strategies, elongation sequences, and protecting group patterns are discussed, but also (semi)automated syntheses, enzymatic approaches, and functionalizations of synthesized or isolated GAGs are considered. PMID- 27410266 TI - Characterizing gold nanorods in aqueous solution by acoustic vibrations probed with four-wave mixing. AB - We demonstrate continuous-wave four-wave mixing to probe the acoustic vibrations of gold nanorods in aqueous solution. The nonlinear optical response of gold nanorods, resonantly enhanced by electrostriction coupling to the acoustic vibration modes, shows an extensional vibration which combines an expansion along the long axis with a contraction along the short axis. We also observed the extensional vibration of gold nanospheres as byproducts of the gold nanorod synthesis. Theoretical calculation of the nanoparticle size and distribution based on the vibrational frequency agrees well with the experimental results obtained from the scanning electron microscopic examination, indicating the four wave mixing technique can provide in situ nanoparticle characterization. PMID- 27410267 TI - Lasing of whispering gallery modes in optofluidic microcapillaries. AB - This paper demonstrates lasing of the whispering gallery modes in polymer coated optofluidic capillaries and their application to refractive index sensing. The laser gain medium used here is fluorescent Nile Red dye, which is embedded inside the high refractive index polymer coating. We investigate the refractometric sensing properties of these devices for different coating thicknesses, revealing that the high Q factors required to achieve low lasing thresholds can only be realized for relatively thick polymer coatings (in this case >= 800 nm). Lasing capillaries therefore tend to have a lower refractive index sensitivity, compared to non-lasing capillaries which can have a thinner polymer coating, due to the stronger WGM confinement within the polymer layer. However we find that the large improvement in signal-to-noise ratio realized for lasing capillaries more than compensates for the decreased sensitivity and results in an order-of-magnitude improvement in the detection limit for refractive index sensing. PMID- 27410265 TI - LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome. AB - Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3' end of the gene body. We also identified a subset of LHP1 activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns. PMID- 27410268 TI - Development of a large plano-elliptical neutron-focusing supermirror with metallic substrates. AB - Results of this study demonstrated that electroless nickel-phosphorus (NiP) plated metal substrate is an excellent material for producing large aspherical neutron-focusing supermirrors. A large plano-elliptical neutron-focusing supermirror comprising two metallic segments was fabricated using single-point diamond cutting, precision polishing and supermirror coating. The average surface roughness of the metallic substrates was approximately 0.3 nm rms. For evaluation, the focusing supermirror was installed at the SOFIA neutron reflectometer, showing high neutron reflectivity and giving minimal beam width of 0.34 mm in FWHM. Because of the large beam divergence accepted by the mirror, the count rate with the focusing mirror was 3.3 times higher than that obtained using conventional two-slit collimation. PMID- 27410269 TI - Momentum-dependent group velocity of surface plasmon polaritons in two dimensional metallic nanohole array. AB - We determine the momentum-dependent group velocities of ( +/- 1,0) and (0, +/- 1) Bloch-like surface plasmon polaritons (SPPs) in two-dimensional Au nanohole array by measuring their propagation lengths and decay lifetimes at different SPP propagation length via angle- and polarization-resolved reflectivity spectroscopy and real- and Fourier-space microscopy. We find the decay length and lifetime, as well as group velocity, are highly dependent on the propagation direction. In particular, close to the Gamma-M direction where two SPPs begin to interfere, the group velocity decreases due to the increase of the standing wave character. More importantly, the two SPPs are strongly interacted with each other at the Gamma-M direction, resulting in forming the dark and bright modes. We find the group velocity of the dark mode is higher that of the bright mode despite its higher quality factor, or longer decay lifetime. We attribute such difference to the distinct field symmetries of dark and bright modes, yielding different effective indices. While bright mode has fields mostly concentrated at the flat metal region to produce higher effective index and therefore lower velocity, the fields of the dark mode are located near the air hole, resulting in higher velocity. PMID- 27410270 TI - Aluminum nitride electro-optic phase shifter for backend integration on silicon. AB - An AlN electro-optic phase shifter with a parallel plate capacitor structure is fabricated on Si using the back-end complementary metal-oxide-semiconductor technology, which is feasible for multilayer photonics integration. The modulation efficiency (Vpi?Lpi product) measured from the fabricated waveguide-ring resonators and Mach-Zehnder Interferometer (MZI) modulators near the 1550-nm wavelength is ~240 V?cm for the transverse electric (TE) mode and ~320 V?cm for the transverse magnetic (TM) mode, from which the Pockels coefficient of the deposited AlN is deduced to be ~1.0 pm/V for both TE and TM modes. The methods for further modulation efficiency improvement are addressed. PMID- 27410271 TI - All-optical flip-flop operation based on bistability in V-cavity laser. AB - We theoretically analyzed and experimentally demonstrated an injection-locking based all-optical flip-flop memory using a simple and compact tunable V-cavity laser (VCL). A bistable region in the tuning characteristics of the VCL is employed for the flip-flop operation. The state of the VCL can be set and reset by injecting signal pulses at two different wavelengths. The pulse power for both set and reset signal is only about 1 pJ. Short response times of about 150 ps are measured for storing and erasing. PMID- 27410272 TI - Characterization of fiber ultrashort pulse delivery for nonlinear endomicroscopy. AB - In this work, we present a detailed characterization of a small-core double-clad photonic crystal fiber, dedicated and approved for in vivo nonlinear imaging endomicroscopy. A numerical and experimental study has been performed to characterize the excitation and collection efficiencies through a 5 m-long optical fiber, including the pulse duration and spectral shape. This was first done without any distal optics, and then the performances of the system were studied by using two kinds of GRIN lenses at the fiber output. These results are compared to published data using commercial double clad fibers and GRIN lenses. PMID- 27410273 TI - Photonic microwave waveform generation based on phase modulation and tunable dispersion. AB - Photonic generation of microwave waveforms is currently an interesting topic due to the advantages of large bandwidth and immunity to electromagnetic interference. In this paper, a photonic microwave waveform generator with tunable waveforms and repetition rates is proposed and experimentally demonstrated. A continuous-wave (CW) light is phase modulated by a local oscillator (LO) signal to generate optical sidebands. By locating the phase modulator (PM) in a Sagnac loop, we can control the intensity and phase of the carrier of the phase modulated signal. Then a compact tunable dispersion compensation module is used to introduce phase shifts to the optical sidebands. Thanks to the flexible controlling of the optical signal, the generation of microwave waveforms with tunable shapes and repetition rates can be realized. In the demonstration experiment, full-duty-cycle triangular and square waveforms with repetition rates of 5 and 10 GHz (bandwidths of 15 and 30 GHz) are successfully generated, respectively. The bandwidths are expected to be improved to above 120 GHz if larger-bandwidth measurement instruments are used. In addition to the flexible tunability, the proposed scheme also features the advantages of easy implementation and free from bias drift. PMID- 27410274 TI - Discrimination of orbital angular momentum modes of the terahertz vortex beam using a diffractive mode transformer. AB - We present an efficient method to discriminate orbital angular momentum (OAM) of the terahertz (THz) vortex beam using a diffractive mode transformer. The mode transformer performs a log-polar coordinate transformation of the input THz vortex beam, which consists of two 3D-printed diffractive elements. A following lens separates each transformed OAM mode to a different lateral position in its focal plane. This method enables a simultaneous measurement over multiple OAM modes of the THz vortex beam. We experimentally demonstrate the measurement of seven individual OAM modes and two multiplexed OAM modes, which is in good agreement with simulations. PMID- 27410275 TI - Post-trimming of photonic crystal nanobeam cavities by controlled electron beam exposure. AB - We theoretically and experimentally demonstrated that the resonant wavelength of photonic crystal (PhC) nanobeam cavities can be individually post tuned by selective electron beam exposure and development. By exposing the SU-8 cladding with different doses, the thickness of the SU-8 can be precisely and individually controlled from 150 nm to 650 nm. The phenomenon is employed in the localized control of the cladding layer from above the cavity region, thereby modifying the resonant wavelengths. The transmission spectrums of the PhC nanobeam cavities are measured before exposure, after exposure and after development, respectively. Utilizing the proposed method, the resonant wavelengths of the PhC nanobeam cavities can be post-tuned as large as 30 nm. This method is applicable to the post-trimming adjustment of the frequency response of the silicon-photonic filters. PMID- 27410276 TI - Experimental demonstration of highly sensitive optical sensor based on grating assisted light coupling between strip and slot waveguides. AB - An optical sensor based on grating-assisted light coupling between a strip waveguide and a slot waveguide is demonstrated (the sensor was proposed and analyzed in [Opt. Express21, 5897-5909 (2013)]. The wavelength at which the light is strongly coupled between two waveguides is used to the measure the external medium's refractive index. The sensor was fabricated with silicon nitride waveguides and obvious grating induced band-rejection and band-pass characteristics were observed. The measured sensitivity of the fabricated sensor was -756.1 nm/RIU. Furthermore, by covering the strip waveguide with the silicon dioxide cladding, the sensitivity was measured to be as large as -1970 nm/RIU, which was 2.6 times enhanced. The experimental results agreed well with the calculated sensitivity values. PMID- 27410277 TI - High-average-power green laser using Nd:YAG amplifier with stimulated Brillouin scattering phase-conjugate pulse-cleaning mirror. AB - We present a high-average-power green laser based on second harmonic conversion of a laser diode-pumped master oscillator Nd:YAG power amplifier system. The power amplifier chain includes a stimulated Brillouin scattering (SBS) cell that was used a phase-conjugate mirror to double-pass scheme. That suppresses the thermal phase distortion and compresses the pulse duration. The fundamental beam output power was 670 W with a pulse width of 7.9 ns. A second harmonic power of 335 W with a 4.8-ns pulse width and 80-mJ pulse energy was produced using a LiB3O5 (LBO) crystal. PMID- 27410278 TI - Depth profiles in confocal optical microscopy: a simulation approach based on the second Rayleigh-Sommerfeld diffraction integral. AB - A method is presented for recovering the intensity depth profile, by confocal optical microscopy, in transparent and amorphous samples with low scattering. The response function of a confocal Raman microscope has been determined by using the second Rayleigh-Sommerfeld diffraction integral and scalar wave optics within paraxial approximation, taking into account the refractive index mismatch between the sample and the medium surrounding the objective lens. An iterative multi fitting-scheme, based on the conjugate gradient method and Brent algorithm, allowed to fit several depth profile curves simultaneously and retrieve the beam waist, the signal amplitude and the position of the sample surface. The reliability and accuracy of the theoretical procedure has been investigated through comparison with experimental measurements of the Raman depth profiles for different pinhole diameters. The model is shown to provide accurate description of the effect of the mismatch of the refractive index and of the dependence of the Raman signal on the depth with discrepancies lower than 3%. This procedure constitutes a first step towards the development of a manageable theoretical framework, amenable to a relatively simple numerical implementation, for the solution of the 'inverse' problem of finding the correct reconstruction of unknown profiles of chemical species within the sample, starting from experimental information gathered from micro-Raman depth profiling. PMID- 27410279 TI - Low-complexity joint symbol synchronization and sampling frequency offset estimation scheme for optical IMDD OFDM systems. AB - A low-complexity joint symbol synchronization and SFO estimation scheme for asynchronous optical IMDD OFDM systems based on only one training symbol is proposed. Numerical simulations and experimental demonstrations are also under taken to evaluate the performance of the mentioned scheme. The experimental results show that robust and precise symbol synchronization and the SFO estimation can be achieved simultaneously at received optical power as low as 20dBm in asynchronous OOFDM systems. SFO estimation accuracy in MSE can be lower than 1 * 10-11 under SFO range from -60ppm to 60ppm after 25km SSMF transmission. Optimal System performance can be maintained until cumulate number of employed frames for calculation is less than 50 under above-mentioned conditions. Meanwhile, the proposed joint scheme has a low level of operation complexity comparing with existing methods, when the symbol synchronization and SFO estimation are considered together. Above-mentioned results can give an important reference in practical system designs. PMID- 27410280 TI - Gas concentration measurement by optical similitude absorption spectroscopy: methodology and experimental demonstration. AB - We propose a new methodology to measure gas concentration by light-absorption spectroscopy when the light source spectrum is larger than the spectral width of one or several molecular gas absorption lines. We named it optical similitude absorption spectroscopy (OSAS), as the gas concentration is derived from a similitude between the light source and the target gas spectra. The main OSAS novelty lies in the development of a robust inversion methodology, based on the Newton-Raphson algorithm, which allows retrieving the target gas concentration from spectrally-integrated differential light-absorption measurements. As a proof, OSAS is applied in laboratory to the 2nu3 methane absorption band at 1.66 um with uncertainties revealed by the Allan variance. OSAS has also been applied to non-dispersive infra-red and the optical correlation spectroscopy arrangements. This all-optics gas concentration retrieval does not require the use of a gas calibration cell and opens new tracks to atmospheric gas pollution and greenhouse gases sources monitoring. PMID- 27410281 TI - 0.6-3.2 MUm supercontinuum generation in a step-index germania-core fiber using a 4.4 kW peak-power pump laser. AB - An ultra-broadband supercontinuum was generated in a short piece of step-index germania-core fiber using a fiber laser with a peak power of 4.4 kW. The pure germania core made this fiber capable of propagating light towards the desirable mid-infrared region. The spectral broadening characteristics towards the mid infrared region under different lengths of germania-core fiber were investigated using pump pulses of 4.4 kW and 1.1 ns at 1550 nm. The large nonlinear refractive index of germania and the small core size of germania-core fiber produced a nonlinear coefficient as high as 11.8 (W km)-1 at 1550 nm, which was beneficial for supercontinuum generation. The pump wavelength was located in the anomalous dispersion regime and close to the zero dispersion wavelength of this germania-core fiber, 1.426 MUm. Eventually, an ultra-broadband supercontinuum source with a spectrum spanning from 0.6 to 3.2 MUm was obtained and had a total output power of 350 mW at an optimized germania-core fiber length of 0.8 m. This work is the first demonstration, to the best of our knowledge, of a germania-core fiber-based ultra-broadband supercontinuum source that spans from the visible region to the mid-infrared region. PMID- 27410282 TI - Non-classical photon correlation in a two-dimensional photonic lattice. AB - Quantum interference and quantum correlation, as two main features of quantum optics, play an essential role in quantum information applications, such as multi particle quantum walk and boson sampling. While many experimental demonstrations have been done in one-dimensional waveguide arrays, it remains unexplored in higher dimensions due to tight requirement of manipulating and detecting photons in large-scale. Here, we experimentally observe non-classical correlation of two identical photons in a fully coupled two-dimensional structure, i.e. photonic lattice manufactured by three-dimensional femtosecond laser writing. Photon interference consists of 36 Hong-Ou-Mandel interference and 9 bunching. The overlap between measured and simulated distribution is up to 0.890 +/- 0.001. Clear photon correlation is observed in the two-dimensional photonic lattice. Combining with controllably engineered disorder, our results open new perspectives towards large-scale implementation of quantum simulation on integrated photonic chips. PMID- 27410283 TI - Numerical method to digital photoelasticity using plane polariscope. AB - This research aims to find a new way to get the intensity equations for the phase shifting model in digital photoelasticity. The procedure is based on the rotation of the analyzer itself. From the intensity equations, the isoclinic and isochromatic equations parameters are deduced by applying a new numerical technique. This approach can be done to calculate how many images allow the resolution of the polariscope. Each image indicates the stress forces in the object. In this study the plane polariscope was used. The amount of images will determinate the number of errors and uncertainties of the study, due to the observation that the veracity of the equations increases considerably with a large amout of images. Several analyses are performed with different amounts of photographic images. The results showed the possibility to measure stress forces with high precision using plane polariscopes. PMID- 27410284 TI - Reconfigurable photonic integrated mode (de)multiplexer for SDM fiber transmission. AB - Spatial division multiplexing in multi-mode fibers allows to largely enhance transmission capacity compared to single-mode links. Photonic integrated circuits can provide solutions for mode multiplexing at the transmitter and demultiplexing at the receiver but have to generally face high losses and inter-modal cross-talk issues. Here a photonic circuit for efficient mode multiplexing and demultiplexing in few-mode fibers is presented and demonstrated. Two 10 Gbit/s channels at the same wavelength and polarization are simultaneously transmitted over modes LP01 and LP11a of a few-mode fiber relying only on integrated mode MUX and DEMUX. The proposed Indium-Phosphide-based circuits have a good coupling efficiency with fiber modes and mode-dependant loss smaller than 1 dB. Measured mode excitation cross-talk is as low as -20 dB and a channel cross-talk after propagation and demultiplexing of -15 dB is achieved. An operational bandwidth of the full transmission system of at least 10 nm is demonstrated. Both mode MUX and DEMUX are fully reconfigurable and allow a dynamic switch of channel routing in the transmission system. These results enable fully-integrated fiber mode handling for high-bandwidth flexible optical networks. PMID- 27410285 TI - Chip based common-path optical coherence tomography system with an on-chip microlens and multi-reference suppression algorithm. AB - We demonstrate an integrated optical probe including an on-chip microlens for a common-path swept-source optical coherence tomography system. This common-path design uses the end facet of the silicon oxynitride waveguide as the reference plane, thus eliminating the need of a space-consuming and dispersive on-chip loop reference arm, thereby obviating the need for dispersion compensation. The on chip micro-ball lens eliminates the need of external optical elements for coupling the light between the chip and the sample. The use of this lens leads to a signal enhancement up to 37 dB compared to the chip without a lens. The light source, the common-path arm and the detector are connected by a symmetric Y junction having a wavelength independent splitting ratio (50/50) over a much larger bandwidth than can be obtained with a directional coupler. The signal-to noise ratio of the system was measured to be 71 dB with 2.6 mW of power on a mirror sample at a distance of 0.3 mm from the waveguide end facet. Cross sectional OCT images of a layered optical phantom sample are demonstrated with our system. A method, based on an extended Fourier-domain OCT model, for suppressing ghost images caused by additional parasitic reference planes is experimentally demonstrated. PMID- 27410286 TI - Low temperature diode pumped active mirror Yb3+:YAG disk laser amplifier studies. AB - An experimental study of a static helium gas gap heat switch concept for laser amplification is presented. High single pass gains with large co-sintered ceramic Yb:YAG disks are recorded in the 80-200K temperature range on a diode pumped active mirror amplifier. PMID- 27410287 TI - Multi-aperture digital coherent combining for free-space optical communication receivers. AB - Space-to-ground optical communication systems can benefit from reducing the size, weight, and power profiles of space terminals. One way of reducing the required power-aperture product on a space platform is to implement effective, but costly, single-aperture ground terminals with large collection areas. In contrast, we present a ground terminal receiver architecture in which many small less expensive apertures are efficiently combined to create a large effective aperture while maintaining excellent receiver sensitivity. This is accomplished via coherent detection behind each aperture followed by digitization. The digitized signals are then combined in a digital signal processing chain. Experimental results demonstrate lossless coherent combining of four lasercom signals, at power levels below 0.1 photons/bit/aperture. PMID- 27410288 TI - Brillouin optical time-domain analysis sensor with pump pulse amplification. AB - We demonstrate a simple technique to provide conventional Brillouin optical time domain analysis sensors with mitigation for pump pulse attenuation. The technique is based on operating the sensor in loss configuration so that energy is transferred from the probe wave to the pump pulse that becomes amplified as it counter-propagates with the probe wave. Furthermore, the optical frequency of the probe wave is modulated along the fiber so that the pump pulse experiences a flat total gain spectrum that equally amplifies all the spectral components of the pulse, hence, preventing distortion. This frequency modulation of the probe brings additional advantages because it provides increased tolerance to non-local effects and to spontaneous Brillouin scattering noise, so that a probe power above the Brillouin threshold of the fiber can be safely deployed, hence, increasing the signal-to-noise ratio of the measurement. The method is experimentally demonstrated in a 100-km fiber link, obtaining a measurement uncertainty of 1 MHz at the worst-contrast position. PMID- 27410289 TI - Spatially and spectrally resolved particle swarm optimization for precise optical property estimation using diffuse-reflectance spectroscopy. AB - This paper presents a new approach to estimate optical properties (absorption and scattering coefficients ua and us) of biological tissues from spatially-resolved spectroscopy measurements. A Particle Swarm Optimization (PSO)-based algorithm was implemented and firstly modified to deal with spatial and spectral resolutions of the data, and to solve the corresponding inverse problem. Secondly, the optimization was improved by fitting exponential decays to the two best points among all clusters of the "particles" randomly distributed all over the parameter space (us, ua) of possible solutions. The consequent acceleration of all the groups of particles to the "best" curve leads to significant error decrease in the optical property estimation. The study analyzes the estimated optical property error as a function of the various PSO parameter combinations, and several performance criteria such as the cost-function error and the number of iterations in the algorithms proposed. The final one led to error values between ground truth and estimated values of us and ua less than 6%. PMID- 27410290 TI - DMD-based software-configurable spatially-offset Raman spectroscopy for spectral depth-profiling of optically turbid samples. AB - Spectral depth-profiling of optically turbid samples is of high interest to a broad range of applications. We present a method for measuring spatially-offset Raman spectroscopy (SORS) over a range of length scales by incorporating a digital micro-mirror device (DMD) into a sample-conjugate plane in the detection optical path. The DMD can be arbitrarily programmed to collect/reject light at spatial positions in the 2D sample-conjugate plane, allowing spatially offset Raman measurements. We demonstrate several detection geometries, including annular and simultaneous multi-offset modalities, for both macro- and micro-SORS measurements, all on the same instrument. Compared to other SORS modalities, DMD based SORS provides more flexibility with only minimal additional experimental complexity for subsurface Raman collection. PMID- 27410291 TI - X-SEA-F-SPIDER characterization of over octave spanning pulses in the infrared range. AB - We show a practical implementation of a pulse characterization method for sub cycle pulse measurements in the infrared spectral range based on spectral shearing interferometry. We employ spatially-encoded arrangement filter-based spectral phase interferometry for direct electric field reconstruction with external ancila pulses (X-SEA-F-SPIDER). We show merits and limitations of the setup and an in-depth comparison to another widely used temporal characterization technique - Second-Harmonic Generation Frequency Resolved Optical Gating (SHG FROG). The X-SEA-F-SPIDER implementation presented in this paper allows measurement of sub-cycle pulses with over one octave wide spectrum spanning the 900-2400 nm range without adding any extra dispersion due to the pulse characterization apparatus. PMID- 27410292 TI - New optical gating technique for detection of electric field waveforms with subpicosecond resolution. AB - The new optical gating technique uses a femtosecond optical laser pulses for the photoconductive detection of short pulses of terahertz (THz) radiation. This technique reproduces the shape of the THz pulse and after pulse plasmonic response of the two-dimensional electron gas in a short channel high electron mobility transistor (HEMT). The results are in excellent agreement with the electro-optic effect measurements and with the simulation results obtained in the frame of a two-dimensional hydrodynamic model. The femtosecond optical laser pulse time is delayed with respect to the THz pulse and generates a large concentration of the electron-hole pairs in the AlGaAs/InGaAs HEMT. This drastically increases the channel conductivity on the femtosecond scale and effectively shorts the device quenching the transistor response. The achieved time resolution is better than 250 femtoseconds and could be improved using shorter femtosecond laser pulses. The spatial resolution of this technique is on the order of tens of nanometers or even smaller. It could be applied for studying the electron transport in a variety of electronic devices ranging from silicon MOSFETs to heterostructure bipolar transistors. PMID- 27410293 TI - Composite Thue-Morse zone plates. AB - We present a new family of diffractive lenses, composite Thue-Morse zone plates (CTMZPs), formed by multiple orders of Thue-Morse zone plates (TMZPs). The typical structure of a CTMZP is a composite of two concentric TMZPs. The focusing properties of the CTMZPs with different parameters have been investigated both theoretically and experimentally. Compared with the TMZPs, the CTMZPs have higher performance in axial intensity and imaging resolution. The CTMZP beams are also found to possess the self-reconstruction property, and would be useful for three dimensional optical tweezers, laser machining, and optical imaging. PMID- 27410294 TI - Plasmonic random lasing in polymer fiber. AB - A random fiber laser is achieved based on the plasmonic feedback mechanism, which is constructed by first siphoning the polymer solution doped with silver nanoparticles into a 300-MUm capillary tube and then evaporating the solvent. Strong amplification of the radiation can be obtained by employing the variable gain region, the fiber waveguide scheme and three-dimensional plasmonic feedback provided by the silver nanoparticles. Low-threshold directional random lasing is observed in the polymer fiber. This simple and straightforward approach facilitates the investigation of plasmonic random fiber lasers. PMID- 27410295 TI - Broadening the detection view of 2D photoacoustic tomography using two linear array transducers. AB - Although commercial linear array transducers are widely used in clinical ultrasound, their application in photoacoustic tomography (PAT) is still limited due to the limited-view problem that restricts the image quality. In this paper, we propose a simple approach to address the limited-view problem in 2D by using two linear array transducers to receive PAT signal from different orientations. The positions of the two transducers can be adjusted to fit the specific geometry of an imaging site. This approach is made possible by using a new calibration method, where the relative position between the two transducers can be calibrated using ultrasound by transmitting ultrasound wave with one transducer while receiving with the other. The calibration results are then applied in the subsequent PAT imaging to incorporate the detected acoustic signals from both transducers and thereby increase the detection view. In this calibration method, no calibration phantom is required which largely simplifies and shortens the process. The efficacy of the calibration and improvement on the PAT image quality are demonstrated through phantom studies and in vivo imaging. PMID- 27410296 TI - Very high-capacity short-reach VCSEL systems exploiting multicarrier intensity modulation and direct detection. AB - Multicarrier intensity modulation of a bandwidth-limited long-wavelength VCSEL is exploited combined to direct detection to achieve very high capacity simple systems for short-reach applications. Tailored FDM subcarriers modulation and allocation allow to match the non-uniform frequency response of the system induced by the direct modulation and detection of the FDM signal and by the uncompensated SSMF propagation, overcoming the VCSEL bandwidth limitations. A whole transported throughput ranging from 34 Gb/s to 25 Gb/s from few hundreds meters to 20 km of SSMF propagation is experimentally demonstrated even by employing a 5-GHz band VCSEL source. PMID- 27410297 TI - Phase retrieval based on temporal and spatial hybrid matching in simultaneous phase-shifting dual-wavelength interferometry. AB - In simultaneous phase-shifting dual-wavelength interferometry, by matching both the phase-shifting period number and the fringe number in interferogram of two wavelengths to the integers, the phase with high accuracy can be retrieved through combining the principle component analysis (PCA) and least-squares iterative algorithm (LSIA). First, by using the approximate ratio of two wavelengths, we can match both the temporal phase-shifting period number and the spatial fringe number in interferogram of two wavelengths to the integers. Second, using above temporal and spatial hybrid matching condition, we can achieve accurate phase shifts of single-wavelength of phase-shifting interferograms through using PCA algorithm. Third, using above phase shifts to perform the iterative calculation with the LSIA method, the wrapped phases of single-wavelength can be determined. Both simulation calculation and experimental research demonstrate that by using the temporal and spatial hybrid matching condition, the PCA + LSIA based phase retrieval method possesses significant advantages in accuracy, stability and processing time. PMID- 27410298 TI - Design and calibration of a digital Fourier holographic microscope for particle sizing via goniometry and optical scatter imaging in transmission. AB - Goniometry and optical scatter imaging have been used for optical determination of particle size based upon optical scattering. Polystyrene microspheres in suspension serve as a standard for system validation purposes. The design and calibration of a digital Fourier holographic microscope (DFHM) are reported. Of crucial importance is the appropriate scaling of scattering angle space in the conjugate Fourier plane. A detailed description of this calibration process is described. Spatial filtering of the acquired digital hologram to use photons scattered within a restricted angular range produces an image. A pair of images, one using photons narrowly scattered within 8 - 15 degrees (LNA), and one using photons broadly scattered within 8 - 39 degrees (HNA), are produced. An image based on the ratio of these two images, OSIR = HNA/LNA, following Boustany et al. (2002), yields a 2D Optical Scatter Image (OSI) whose contrast is based on the angular dependence of photon scattering and is sensitive to the microsphere size, especially in the 0.5-1.0um range. Goniometric results are also given for polystyrene microspheres in suspension as additional proof of principle for particle sizing via the DFHM. PMID- 27410299 TI - Densely-tiled metal-insulator-metal metamaterial resonators with quasi- monochromatic thermal emission. AB - Metal-insulator-metal metamaterial thermal emitters strongly radiate at multiple resonant wavelengths. The fundamental mode, whose wavelength is the longest among resonances, is generally utilized for selective emission. In this paper, we show that parasitic modes at shorter wavelengths are suppressed by newly employed densely-tiled resonators, and that the suppression enables quasi-monochromatic thermal emission. The second-order harmonics, which is excited at half the fundamental wavelength in conventional emitters, shifts toward shorter wavelength. The blue-shift reduces the amplitude of the second-order emission by taking a distance from the Wien wavelength. Other parasitic modes are eliminated by the small spacing between resonators. The densely-tiled resonators are fabricated, and the measured emission spectra agree well with numerical simulations. The methodology presented here for the suppression of parasitic modes adds flexibility to metamaterial thermal emitters. PMID- 27410300 TI - Surface plasmon resonance prism coupler for enhanced circular dichroism sensing. AB - A novel method for enhanced circular dichroism (CD) detection is proposed based on a surface plasmon resonance (SPR) prism coupler and a polarization scanning ellipsometry technique. An analytical model is derived to extract the CD and degree of polarization (DOP) properties of optical samples with and without scattering effects, respectively. The validity of the analytical model is confirmed by means of numerical simulations. The simulation results show that the proposed detection method has a sensitivity of 10-5~10-6 RIU (refractive index unit) for refractive indices in the range of 1.32~1.36 and 1.3100~1.3118. The practical feasibility of the proposed method is demonstrated by the experimental results for the sensitivity of the CD with the chlorophyllin samples with/without scattering effect. It is shown that for both types of sample, the extracted CD value increases linearly with the chlorophyll concentration over the considered range. In general, the results obtained in this study show that the measured CD response is highly sensitive to the polarization scanning angle. Consequently, the potential of polarization scanning ellipsometry for high-resolution CD detection is confirmed. PMID- 27410301 TI - Nonlinear Cherenkov radiation at the interface of two different nonlinear media. AB - We discuss the nonlinear response due to the spatial modulation of the second order susceptibility at the interface between two nonlinear media, and experimentally demonstrate that the nonlinear Cherenkov radiation is enhanced by the interface of two nonlinear crystals with a large disparity in chi(2). In our experiment, the intensity of the nonlinear Cherenkov radiation generated at the nonlinear interface was approximately 4 to 10 times that at the crystal boundary. This result suggests potential applications to efficient frequency conversion. PMID- 27410302 TI - Tunable spiral Bragg gratings in 60-nm-thick silicon-on-insulator strip waveguides. AB - We demonstrate spiral integrated Bragg gratings (IBGs) in 60-nm-thick strip waveguides on the silicon-on-insulator (SOI) platform. The length of the spiral IBG is 2 mm, occupying an area of 147 * 141 MUm2 with a minimum bending radius of 20 MUm. Experiments show that the spiral IBGs exhibit a single narrow transparent peak with a Q-factor of 1 * 105 in a broad stopband, induced by the phase shift of the S-junction at the spiral center. This phenomenon is analogous to the electromagnetically induced transparency (EIT) effect. The transparent peak can periodically shift in the stopband upon heating of the S-junction using a TiN-based heater on top. The peak transmittance and Q factor are dependent on the reflectivity of the spiral IBG. The transparent peak can be completely eliminated under a certain tuning power, and the spiral IBG hence behaves as a bandstop optical filter. The bandwidth is 0.94 nm and the extinction ratio is as high as 43 dB. The stopband can also be shifted by heating the Bragg gratings using a separate TiN heater. The experimental results agree well with the modeling results based on the transfer matrix method. PMID- 27410303 TI - Investigation of beam steering performances in rotation Risley-prism scanner. AB - Rotation Risley-prism scanner appears to be the most promising solution to high accuracy beam scanning and target tracking. In the paper, some important issues crucial to the function implementation are thoroughly investigated. First the forming law of scan blind zone relative to double-prism structural parameters is explored by a quantitative analysis method. Then the nonlinear relationship between the rotation speeds of double prisms and the change rate of beam deviation angle is presented, and the beam scan singularity is indicated as an essential factor that confines the beam scan region. Finally, the high-accuracy radial scan theory is verified to illustrate the important application owing to the high reduction ratio from the rotation angles of double prisms to the deviation angles of the emergent beam. The research not only reveals the inner mechanisms of the Risley-prism beam scanning in principle, but also provide a foundation for the nonlinear control of various beam scan modes. PMID- 27410304 TI - High efficiency passively mode-locked Nd:YVO4 laser with direct in band pumping at 914 nm. AB - We report on the performance of a semiconductor saturable absorber mirror passively mode-locked Nd:YVO4 laser with in-band pumping at 914 nm and with the highest slope efficiency to date among the mode-locked Nd-lasers. The laser produced 6.7 W of output power with repetition rate of 87 MHz and pulse duration of 16 ps. The slope efficiency of 77.1% and the optical-to-optical efficiency of 60.7% were achieved. PMID- 27410305 TI - Design of a compact waveguide optical isolator based on multimode interferometers using magneto-optical oxide thin films grown on silicon-on-insulator substrates. AB - We report the design of a waveguide optical isolator based on multimode interferometer (MMI) structure using silicon on insulator (SOI) and deposited magneto-optical (MO) thin films. The optical isolator is based on a vertical 1 * 2 SOI MMI utilizing the nonreciprocal phase shift (NRPS) difference of different TM modes of the MO garnet thin film/SOI waveguide. By constructing a silicon/MO thin film/silicon structure, we demonstrate that the NRPS of the fundamental and first order TM modes can show opposite signs for certain device dimensions, therefore significantly reduce the device length. For a 310.42 MUm long device, 20 dB isolation bandwidth larger than 1.6 nm with total insertion loss of 0.817 dB is achieved at 1550 nm wavelength. The fabrication tolerances and materials losses are also discussed to satisfy the state-of-the-art fabrication technology and material properties. PMID- 27410306 TI - Depth map generation using a single image sensor with phase masks. AB - Conventional stereo matching systems generate a depth map using two or more digital imaging sensors. It is difficult to use the small camera system because of their high costs and bulky sizes. In order to solve this problem, this paper presents a stereo matching system using a single image sensor with phase masks for the phase difference auto-focusing. A novel pattern of phase mask array is proposed to simultaneously acquire two pairs of stereo images. Furthermore, a noise-invariant depth map is generated from the raw format sensor output. The proposed method consists of four steps to compute the depth map: (i) acquisition of stereo images using the proposed mask array, (ii) variational segmentation using merging criteria to simplify the input image, (iii) disparity map generation using the hierarchical block matching for disparity measurement, and (iv) image matting to fill holes to generate the dense depth map. The proposed system can be used in small digital cameras without additional lenses or sensors. PMID- 27410307 TI - Cost-effective coherent ONU transceiver based on single directly modulated laser. AB - A cost-effective structure is proposed for the optical network unit (ONU) transceivers in coherent ultra-dense wavelength division multiplexing passive optical network (UDWDM-PON), which is based on a single directly modulated laser (DML). This is the first time that a DML is used as both optical transmitter in upstream and local oscillator (LO) for coherent detection in downstream. The impact of extinction ratio (ER) of signal from DML is investigated and optimized by adapting the driving amplitude and bias of DML. Each UDWDM grid accommodates a pair of bi-directional signal, where heterodyne detection is used due to the Rayleigh backscattering (RB) from the bi-directional transmission. The impact of frequency offset (FO) between upstream and downstream signal is also investigated. Finally, 2.5-Gb/s bi-directional transmission of OOK signal over 60 km SSMF is experimentally demonstrated within the 12.5-GHz grid, achieving about 43 and -45.5 dBm receiver sensitivity in the downstream and upstream, respectively. PMID- 27410308 TI - Sensitive and selective detection of prostate-specific antigen using a photonic crystal nanolaser. AB - The detection of low-concentration biomarkers is expected to facilitate the early diagnosis of severe diseases, including malignant tumors. Using photonic crystal nanolaser sensors, we detected prostate-specific antigen (PSA) from a concentration of 1 fM, which is difficult to detect by conventional enzyme-linked immunosorbent assay. The signal intensity and stability were improved by using a surfactant (i.e., ethanolamine). Even when a contaminant such as bovine serum albumin was mixed into the PSA sample, thereby increasing the concentration of the contaminant ten billion times, it was still possible to maintain a high level of detection. PMID- 27410309 TI - Single-etch subwavelength engineered fiber-chip grating couplers for 1.3 um datacom wavelength band. AB - We report, for the first time, on the design and experimental demonstration of fiber-chip surface grating couplers based on subwavelength grating engineered nanostructure operating in the low fiber chromatic dispersion window (around 1.3 MUm wavelengths), which is of great interest for short-reach data communication applications. Our coupler designs meet the minimum feature size requirements of large-volume deep-ultraviolet stepper lithography processes. The fiber-chip couplers are implemented in a standard 220-nm-thick silicon-on-insulator (SOI) platform and are fabricated by using a single etch process. Several types of couplers are presented, specifically the uniform, the apodized, and the focusing designs. The measured peak coupling efficiency is -2.5 dB (56%) near the central wavelength of 1.3 MUm. In addition, by utilizing the technique of the backside substrate metallization underneath the grating couplers, the coupling efficiency of up to -0.5 dB (89%) is predicted by Finite Difference Time Domain (FDTD) calculations. PMID- 27410310 TI - Reducing effects of aberration in 3D fluorescence imaging using wavefront coding with a radially symmetric phase mask. AB - In this work, a wavefront encoded (WFE) imaging system built using a squared cubic phase mask, designed to reduce the sensitivity of the imaging system to spherical aberration, is investigated. The proposed system allows the use of a space-invariant image restoration algorithm, which uses a single PSF, to restore intensity distribution in images suffering aberration, such as sample-induced aberration in thick tissue. This provides a computational advantage over depth variant image restoration algorithms developed previously to address this aberration. Simulated PSFs of the proposed system are shown to change up to 25% compared to the 0 um depth PSF (quantified by the structural similarity index) over a 100 um depth range, while the conventional system PSFs change up to 84%. Results from experimental test-sample images show that restoration error is reduced by 29% when the proposed WFE system is used instead of the conventional system over a 30 um depth range. PMID- 27410311 TI - High-speed imaging of sound using parallel phase-shifting interferometry. AB - Sound-field imaging, the visualization of spatial and temporal distribution of acoustical properties such as sound pressure, is useful for understanding acoustical phenomena. This study investigated the use of parallel phase-shifting interferometry (PPSI) with a high-speed polarization camera for imaging a sound field, particularly high-speed imaging of propagating sound waves. The experimental results showed that the instantaneous sound field, which was generated by ultrasonic transducers driven by a pure tone of 40 kHz, was quantitatively imaged. Hence, PPSI can be used in acoustical applications requiring spatial information of sound pressure. PMID- 27410312 TI - Controlled soliton formation in tailored Bessel photonic lattices. AB - Azimuthally modulated higher order rotationally symmetric Bessel-like optical patterns were generated by coherent superposition of two co-propagating Bessel beams - either in or out of phase. By changing the distance between the beam centers, a whole variety of transition states can be realized. As one prominent example, a 4-fold symmetry quadrupole-like photonic structure was optically inducted in an SBN crystal and nonlinear beam propagation in such a photonic wave guiding structure is investigated in both self-focusing and self-defocusing regimes. The proposed device serves as an all-optical 2d 1 * 4 photonic interconnect. PMID- 27410313 TI - 100-Gb/s TWDM-PON based on 10G optical devices. AB - High speed data modulation based on bandwidth limited devices has been considered as a cost-effective way to upgrade 10G-EPON to the next generation 100G-EPON. In this paper, we experimentally demonstrate the modulation, fiber transmission and reception of 25-Gb/s signal based on directly modulated laser and photo-detector both operating at 10 GHz. Instead of digital signal processing, the chirp management, dispersion compensation and frequency equalization in our scheme are realized in optical domain using a single delay interferometer. Three popular formats are investigated, including NRZ-OOK, PAM-4 and duobinary. According to the experimental results, the NRZ-OOK format shows its superiority in both launch power and receiver sensitivity, which provides a cost-effective solution for the construction of 100-Gb/s TWDM-PON. PMID- 27410314 TI - Technique to separate lidar signal and sunlight. AB - Sunlight contamination dominates the backscatter noise in space-based lidar measurements during daytime. The background scattered sunlight is highly variable and dependent upon the surface and atmospheric albedo. The scattered sunlight contribution to noise increases over land and snow surfaces where surface albedos are high and thus overwhelm lidar backscatter from optically thin atmospheric constituents like aerosols and thin clouds. In this work, we developed a novel lidar remote sensing concept that potentially can eliminate sunlight induced noise. The new lidar concept requires: (1) a transmitted laser light that carries orbital angular momentum (OAM); and (2) a photon sieve (PS) diffractive filter that separates scattered sunlight from laser light backscattered from the atmosphere, ocean and solid surfaces. The method is based on numerical modeling of the focusing of Laguerre-Gaussian (LG) laser beam and plane-wave light by a PS. The model results show that after passing through a PS, laser light that carries the OAM is focused on a ring (called "focal ring" here) on the focal plane of the PS filter, very little energy arrives at the center of the focal plane. However, scattered sunlight, as a plane wave without the OAM, focuses at the center of the focal plane and thus can be effectively blocked or ducted out. We also find that the radius of the "focal ring" increases with the increase of azimuthal mode (L) of LG laser light, thus increasing L can more effectively separate the lidar signal away from the sunlight noise. PMID- 27410315 TI - Improving radiation dose efficiency of X-ray differential phase contrast imaging using an energy-resolving grating interferometer and a novel rank constraint. AB - In this paper, a novel method was developed to improve the radiation dose efficiency, viz., contrast to noise ratio normalized by dose (CNRD), of the grating-based X-ray differential phase contrast (DPC) imaging system that is integrated with an energy-resolving photon counting detector. The method exploits the low-dimensionality of the spatial-spectral DPC image matrix acquired from different energy windows. A low rank approximation of the spatial-spectral image matrix was developed to reduce image noise while retaining the DPC signal accuracy for every energy window. Numerical simulations and experimental phantom studies have been performed to validate the proposed method by showing noise reduction and CNRD improvement for each energy window. PMID- 27410316 TI - Experimental study of low-loss single-mode performance in anti-resonant hollow core fibers. AB - Anti-resonant hollow-core fibers are optical fiber waveguides which exhibit very low dispersion, high damage threshold and ultra-low nonlinear response. However, they typically deliver the light in several spatial modes, whereas their application usually requires that they support a single spatial mode. We report the principles, fabrication, demonstration and characterization of anti-resonant hollow-core fibres with strong differential modal attenuations and low overall attenuations. These fibers perform as single-mode and are eminently suitable for delivery of powerful ultrashort optical pulses in machining, cutting, welding and multiphoton microscopy applications. PMID- 27410317 TI - Novel adiabatic tapered couplers for active III-V/SOI devices fabricated through transfer printing. AB - We present the design of two novel adiabatic tapered coupling structures that allow efficient and alignment tolerant mode conversion between a III-V membrane waveguide and a single-mode SOI waveguide in active heterogeneously integrated devices. Both proposed couplers employ a broad intermediate waveguide to facilitate highly alignment tolerant coupling. This robustness is needed to comply with the current misalignment tolerance requirements for high-throughput transfer printing. The proposed coupling structures are expected to pave the way for transfer-printing-based heterogeneous integration of active III-V devices such as semiconductor optical amplifiers (SOAs), photodetectors, electro absorption modulators (EAMs) and single wavelength lasers on silicon photonic integrated circuits. PMID- 27410318 TI - Frequency- and intensity-noise suppression in Yb3+-doped single frequency fiber laser by a passive optical-feedback loop. AB - The frequency and intensity noise of an Yb3+-doped single-frequency distributed Bragg reflector (DBR) fiber laser are effectively reduced by a simple, passive optical-feedback loop (POFL), which consists of only two optical couplers. The feedback loop, which has resonance with the high reflective grating of the DBR laser and relative long optical path compared to the DBR cavity, results in narrower linewidth and lower relative intensity noise (RIN) in the feedback signal. The RIN of relaxation oscillation is reduced by 20dB from 99.9dB/Hz @ 993 kHz to -119.4dB/Hz @ 192 kHz, and the frequency noise was suppressed at frequencies higher than 1 kHz, with a maximum reduction of about 30 dB from 10 kHz to 100 kHz, which results in a spectral linewidth compression from 3.96 kHz to 540 Hz. Even after one fiber amplification stage, the noise did not increase significantly, and a spectral linewidth well below 1 kHz were also achieved at output power of 10W. PMID- 27410319 TI - Observation of reflection feedback induced the formation of bright-dark pulse pairs in an optically pumped semiconductor laser. AB - It is experimentally demonstrated that the tiny reflection feedback can lead the optically pumped semiconductor laser (OPSL) to be operated in a self-mod-locked state with a pulse train of bright-dark pulse pairs. A theoretical model based on the multiple reflections in a phase-locked multi-longitudinal-mode laser is developed to confirm the formation of bright-dark pulse pairs. The present finding can offer an important insight into the temporal dynamics in mode-locked OPSLs. PMID- 27410320 TI - Role of Ce in Yb/Al laser fibers: prevention of photodarkening and thermal effects. AB - We report on detailed investigations of ytterbium (Yb) and aluminum (Al) doped silica fiber and preform samples co-doped with cerium (Ce). The prevention of pump-induced photodarkening (PD) by temporary oxidation of Ce3+ to Ce4+ (or rather Ce3++) was proved by observed modifications in the ultraviolet (UV) spectra of transient absorption during near-infrared (NIR) pumping of thin preform slices. Only a small part of available Ce3+ ions (< 4%) was found to be involved in this process despite Yb inversions of up to 0.28. The modifications in the UV absorption spectra disappeared completely when the pump power was switched-off. From these observations we conclude that the recombination to Ce3+ takes place very fast thereby enabling these ions to capture liberated holes h+ perpetually during further pumping. We found a concentration ratio of Ce/Yb ~0.5 to be sufficient to reduce PD loss to 10% in comparison to Ce-free fibers. Thus, the thermal load caused by absorption of PD color centers at pump (and laser) wavelength is expected to be also reduced. Unfortunately, new heat sources arise with the presence of Ce which cannot be explained by the absorption of Ce ions at the pump wavelength but must be attributed to the interaction with excited Yb ions. Fiber temperature increase of more than 200 K was observed if both, Yb2O3 and Ce2O3 concentration exceed 0.4 mol%. PMID- 27410321 TI - Resolution enhancement for low-temperature scanning microscopy by cryo-immersion. AB - Here we report a simple way to enhance the resolution of a confocal scanning microscope under cryogenic conditions. Using a microscope objective (MO) with high numerical aperture (NA = 1.25) and 1-propanol as an immersion fluid with low freezing temperature we were able to reach an imaging resolution at 160 K comparable to ambient conditions. The MO and the sample were both placed inside the inner chamber of the cryostat to reduce distortions induced by temperature gradients. The image quality of our commercially available MO was further enhanced by scanning the sample (sample scanning) in contrast to beam scanning. The ease of the whole procedure marks an essential step towards the development of cryo high-resolution microscopy and correlative light and electron cryo microscopy (cryoCLEM). PMID- 27410322 TI - Nonlinear optical properties of multilayer graphene in the infrared. AB - A negative value for the nonlinear refraction in graphene is experimentally observed and unambiguously verified by performing a theoretical analysis arising from the conductivity of the graphene monolayer. The nonlinear optical properties of multi-layer graphene are experimentally studied by employing the Z-scan technique. The measurements are carried out at 1150, 1550, 1900 and 2400 nm with a 100-femtosecond laser source. Under laser illumination the multi-layer graphene exhibits a transmittance increase due to saturable absorption, followed by optical limiting due to two-photon absorption. The saturation irradiance Isat and the two-photon absorption coefficient beta are measured in the operating wavelength range. Furthermore, an irradiance-dependent nonlinear refraction is observed and discriminated from the conventional nonlinear refraction coefficient n2, which is not irradiance dependent. The values obtained for the irradiance-dependent nonlinear refraction are in the order of ~10-9 cm2W-1, approximately 8 orders of magnitude larger than any bulk dielectrics. PMID- 27410323 TI - Coherent mid-infrared frequency combs in silicon-microresonators in the presence of Raman effects. AB - We demonstrate the first low-noise mid-IR frequency comb source using a silicon microresonator. Our observation of strong Raman scattering lines in the generated comb suggests that interplay between Raman and four-wave mixing plays a role in the generated low-noise state. In addition, we characterize, the intracavity comb generation dynamics using an integrated PIN diode, which takes advantage of the inherent three-photon absorption process in silicon. PMID- 27410324 TI - Analysis of acousto-optic interaction based on forward stimulated Brillouin scattering in hybrid phononic-photonic waveguides. AB - We present the generation of forward stimulated Brillouin scattering (FSBS) in hybrid phononic-photonic waveguides. To confine the optical and acoustic waves simultaneously, a hybrid waveguide is designed by embedding the silicon line defect in the silicon nitride phononic crystal slab. By taking into account three kinds hybrid waveguide, the appropriate structural parameters are obtained to enhance the acousto-optic interaction. We fabricate the honeycomb hybrid waveguide with a CMOS compatible technology. The forward Brillouin frequency shift is measured up to 2.425 GHz and the acoustic Q-factor of the corresponding acoustic mode is 1100. The influences of pump power, acoustic loss, nonlinear optical loss and lattice constant on the acousto-optic interaction in FSBS are analyzed and discussed. The proposed approach has important potential applications in on-chip all-optical signal processing. PMID- 27410325 TI - Channel capacity and receiver deployment optimization for multi-input multi output visible light communications. AB - Multi-input multi-output (MIMO) technique is attractive for visible light communication (VLC), which exploits the high signal-to-noise ratio (SNR) of a single channel to overcome the capacity limitation due to the small modulation bandwidth of the light emitting diode. This paper establishes a MIMO VLC system under the non-negativity, peak power and dimmable average power constraints. Assume that perfect channel state information at the transmitter is known, the MIMO channel is changed to parallel, non-interfering sub-channels by using the singular value decomposition (SVD). Based on the SVD, the lower bound on the channel capacity for MIMO VLC is derived by employing entropy power inequality and variational method. Moreover, by maximizing the derived lower bound on the capacity under the given constraints, the receiver deployment optimization problem is formulated. The problem is solved by employing the principle of particle swarm optimization. Numerical results verify the derived capacity bound and the proposed deployment optimization scheme. PMID- 27410326 TI - Demonstration of micro-projection enabled short-range communication system for 5G. AB - A liquid crystal on silicon (LCoS) based polarization modulated image (PMI) system architecture using red-, green- and blue-based light-emitting diodes (LEDs), which offers simultaneous micro-projection and high-speed data transmission at nearly a gigabit, serving as an alternative short-range communication (SRC) approach for personal communication device (PCD) application in 5G, is proposed and experimentally demonstrated. In order to make the proposed system architecture transparent to the future possible wireless data modulation format, baseband modulation schemes such as multilevel pulse amplitude modulation (M-PAM), M-ary phase shift keying modulation (M-PSK) and M-ary quadrature amplitude modulation (M-QAM) which can be further employed by more advanced multicarrier modulation schemes (such as DMT, OFDM and CAP) were used to investigate the highest possible data transmission rate of the proposed system architecture. The results demonstrated that an aggregative data transmission rate of 892 Mb/s and 900 Mb/s at a BER of 10^(-3) can be achieved by using 16-QAM baseband modulation scheme when data transmission were performed with and without micro-projection simultaneously. PMID- 27410327 TI - On spectral and temporal coherence of x-ray free-electron laser beams. AB - A model for the coherence properties of free-electron lasers (FELs) in time and frequency domains is introduced within the framework of classical second-order coherence theory of nonstationary light. An iterative phase-retrieval algorithm is applied to construct an ensemble of field realizations in both domains, based on single-pulse spectra measured at the Linac Coherent Light Source (LCLS) in self-amplified spontaneous emission mode. Such an ensemble describes the specific FEL pulse train in a statistically averaged sense. Two-time and two-frequency correlation functions are constructed, demonstrating that the hard X-ray free electron laser at LCLS in this case behaves as a quasistationary source with low spectral and temporal coherence. We also show that the Gaussian Schell model provides a good description of this FEL. PMID- 27410328 TI - Curved gratings as an integrated photon fluence monitor in x-ray transmission scattering experiments. AB - A concept to obtain a measure of the photon flux accepted by a solid sample in single-shot transmission experiments with extreme ultraviolet (XUV) or soft x-ray radiation is demonstrated. Shallow, continuously distorted gratings are used to diffract a constant fraction of the incident photons onto an extended area of a CCD detector. The signal can be tailored to fit the dynamic range of the detector, i.e. matching the scattered intensity of the studied structure of interest. Furthermore, composite grating designs that also allow for the measurement of the spatial photon distribution on the sample are demonstrated. The gratings are directly fabricated by focused ion-beam (FIB) lithography into a Si3N4 membrane that supports the actual sample layer. This allows for rapid fabrication of hundreds of samples, making the concept suitable for systematic studies in destructive single-shot measurements at free-electron laser (FEL) sources. We demonstrate relative photon flux measurements in magnetic scattering experiments with synchrotron and FEL radiation at 59.6 eV photon energy. PMID- 27410329 TI - Model-based restoration of underwater spectral images captured with narrowband filters. AB - Underwater spectral imaging is a promising method for mapping, classification and health monitoring of coral reefs and seafloor inhabitants. However, the spectrum of light is distorted during the underwater imaging process due to wavelength dependent attenuation by the water. This paper presents a model-based method that accurately restores brightness of underwater spectral images captured with narrowband filters. A model is built for narrowband underwater spectral imaging. The model structure is derived from physical principles, representing the absorption, scattering and refraction by water and the optical properties of narrowband filters, lenses and image sensors. The model coefficients are calibrated based on spectral images captured underwater and in air. With the imaging model available, energy loss due to water attenuation is restored for images captured at different underwater distances. An experimental setup is built and experiments are carried out to verify the proposed method. Underwater images captured within an underwater distance of 260 cm are restored and compared with those in air. Results show that the relative restoration error is 3.58% on average for the test images, thus proving the accuracy of the proposed method. PMID- 27410330 TI - Single-shot distributed temperature and strain tracking using direct detection phase-sensitive OTDR with chirped pulses. AB - So far, the optical pulses used in phase-sensitive OTDR (PhiOTDR) were typically engineered so as to have a constant phase along the pulse. In this work, it is demonstrated that by acting on the phase profile of the optical pulses, it is possible to introduce important conceptual and practical changes to the traditional PhiOTDR operation, thus opening a door for new possibilities which are yet to be explored. Using a PhiOTDR with linearly chirped pulses and direct detection, the distributed measurement of temperature/strain changes from trace to trace, with 1mK/4nepsilon resolution, is theoreticaly and experimentaly demonstrated. The measurand resolution and sensitivity can be tuned by acting on the pulse chirp profile. The technique does not require a frequency sweep, thus greatly decreasing the measurement time and complexity of the system, while maintaining the potential for metric spatial resolutions over tens of kilometers as in conventional PhiOTDR. The technique allows for measurements at kHz rates, while maintaining reliability over several hours. PMID- 27410331 TI - Level-crossing and modal structure in microdroplet resonators. AB - We fabricate a liquid-core liquid-clad microcavity that is coupled to a standard tapered fiber, and then experimentally map the whispering-gallery modes of this droplet resonator. The shape of our resonator is similar to a thin prolate spheroid, which makes space for many high-order transverse modes, suggesting that some of them will share the same resonance frequency. Indeed, we experimentally observe that more than half of the droplet's modes have a sibling having the same frequency (to within linewidth) and therefore exhibiting a standing interference pattern. PMID- 27410332 TI - Far-field, linewidth and thermal characteristics of a high-speed 1550-nm MEMS tunable VCSEL. AB - We report an electrically pumped 1550 nm MEMS tunable VCSEL with a continuous tuning of 101 nm at 22 degrees C. The top MEMS-DBR with built-in stress gradient within the dielectric layers is deposited in a low-temperature PECVD chamber on an InP-based half-VCSEL, structured by surface-micromachining and electrothermally actuated for continuous wavelength tuning. With 2.6 mA threshold current, the laser shows maximum CW output power of 3.2 mW at 1560 nm. The MEMS VCSEL operates in single-mode with SMSR > 39 dB across the entire tuning range. At 36 degrees C, the tuning range reaches up to 107 nm. The divergence angle of the MEMS-VCSEL is approximately 5.6 degrees for all tuning wavelengths. The intrinsic linewidth of an unpackaged device is 21 MHz. Quasi-error-free operation at 12.5 Gbps using a directly modulated MEMS-VCSEL is reported for a record 60 nm tuning, showing the potential of the so-called colorless source in WDM applications. PMID- 27410333 TI - Real-time adaptive optics testbed to investigate point-ahead angle in pre compensation of Earth-to-GEO optical communication. AB - We explore adaptive optics (AO) pre-compensation for optical communication between Earth and geostationary (GEO) satellites in a laboratory experiment. Thus, we built a rapid control prototyping breadboard with an adjustable point ahead angle where downlink and uplink can operate both at 1064 nm and 1550 nm wavelength. With our real-time system, beam wander resulting from artificial turbulence was reduced such that the beam hits the satellite at least 66% of the time as compared to merely 3% without correction. A seven-fold increase of the average Strehl ratio to (28 +/- 15)% at 18 MUrad point-ahead angle leads to a considerable reduction of the calculated fading probability. These results make AO pre-compensation a viable technique to enhance Earth-to-GEO optical communication. PMID- 27410334 TI - Freeform aplanatic systems as a limiting case of SMS. AB - We present here aplanatic systems in 3D geometry as a limiting case of a SMS 3D design. We extend the basic formulations governing rotationally symmetric aplanatic systems to freeform aplanatic systems and provide a formal proof that a SMS 3D design in the limiting case of 3 coincident points leads to a freeform aplanatic system. PMID- 27410335 TI - Sensitivity of power and RMS delay spread predictions of a 3D indoor ray tracing model. AB - This study investigates the sensitivity of a three-dimensional (3D) indoor ray tracing (RT) model for the use of the uniform theory of diffraction and geometrical optics in radio channel characterizations of indoor environments. Under complex indoor environments, RT-based predictions require detailed and accurate databases of indoor object layouts and the electrical characteristics of such environments. The aim of this study is to assist in selecting the appropriate level of accuracy required in indoor databases to achieve good trade offs between database costs and prediction accuracy. This study focuses on the effects of errors in indoor environments on prediction results. In studying the effects of inaccuracies in geometry information (indoor object layout) on power coverage prediction, two types of artificial erroneous indoor maps are used. Moreover, a systematic analysis is performed by comparing the predictions with erroneous indoor maps and those with the original indoor map. Subsequently, the influence of random errors on RMS delay spread results is investigated. Given the effect of electrical parameters on the accuracy of the predicted results of the 3D RT model, the relative permittivity and conductivity of different fractions of an indoor environment are set with different values. Five types of computer simulations are considered, and for each type, the received power and RMS delay spread under the same circumstances are simulated with the RT model. PMID- 27410336 TI - fVisiOn: 360-degree viewable glasses-free tabletop 3D display composed of conical screen and modular projector arrays. AB - A novel glasses-free tabletop 3D display to float virtual objects on a flat tabletop surface is proposed. This method employs circularly arranged projectors and a conical rear-projection screen that serves as an anisotropic diffuser. Its practical implementation installs them beneath a round table and produces horizontal parallax in a circumferential direction without the use of high speed or a moving apparatus. Our prototype can display full-color, 5-cm-tall 3D characters on the table. Multiple viewers can share and enjoy its real-time animation from any angle of 360 degrees with appropriate perspectives as if the animated figures were present. PMID- 27410337 TI - Error-free operation of a polarization-insensitive 4lambda x 25 Gbps silicon photonic WDM receiver with closed-loop thermal stabilization of Si microrings. AB - We report the first closed-loop operation of a 100 Gbps polarization-insensitive, 4-channel wavelength-tracking WDM receiver in silicon photonics platform. Error free operation is achieved with input polarization scrambling over input wavelength change of 4.5 nm using efficient thermal tuning of Si microring demux, corresponding to greater than 60 degrees C fluctuation in temperature. PMID- 27410338 TI - Anderson localization in metallic nanoparticle arrays. AB - Anderson localization has been observed in various types of waves, such as matter waves, optical waves and acoustic waves. Here we reveal that the effect of Anderson localization can be also induced in metallic nonlinear nanoparticle arrays excited by a random electrically driving field. We find that the dipole induced nonlinearity results in ballistic expansion of dipole intensity during evolution; while the randomness of the external driving field can suppress such an expansion. Increasing the strength of randomness above the threshold value, a localized pattern of dipole intensity can be generated in the metallic nanoparticle arrays. By means of statistics, the mean intensity distribution of the dipoles reveals the formation of Anderson localization. We further show that the generated Anderson localization is highly confined, with its size down to the scale of incident wavelength. The reported results might facilitate the manipulations of electromagnetic fields in the scale of wavelength. PMID- 27410339 TI - Highly efficient blazed grating with multilayer coating for tender X-ray energies. AB - For photon energies of 1 - 5 keV, blazed gratings with multilayer coating are ideally suited for the suppression of stray and higher orders light in grating monochromators. We developed and characterized a blazed 2000 lines/mm grating coated with a 20 period Cr/C- multilayer. The multilayer d-spacing of 7.3 nm has been adapted to the line distance of 500 nm and the blaze angle of 0.84 degrees in order to provide highest efficiency in the photon energy range between 1.5 keV and 3 keV. Efficiency of the multilayer grating as well as the reflectance of a witness multilayer which were coated simultaneously have been measured. An efficiency of 35% was measured at 2 keV while a maximum efficiency of 55% was achieved at 4 keV. In addition, a strong suppression of higher orders was observed which makes blazed multilayer gratings a favorable dispersing element also for the low X-ray energy range. PMID- 27410340 TI - On the properties of single-mode optical resonators. AB - We study the quality factor of single-mode optical whispering gallery mode resonators using finite element method simulations, with a particular focus on the photonic belt resonator geometry. We experimentally observe a large difference between the quality factors of TM and TE modes in such resonators. Examining radiative losses, we conclude that the TM fundamental mode of single mode resonators can have geometry related radiative losses caused by mode hybridization and coupling that limits their achievable quality factor. However, TE modes are free from mode hybridization radiative losses. This leads to much higher achievable Q factors for TE modes, only limited by fabrication and material quality. We experimentally observed photonic belt resonator quality factors on the order of one billion for TE modes, higher than in any other single mode optical resonator of similar dimensions. PMID- 27410341 TI - Valley-to-peak intensity ratio thermometry based on the red upconversion emission of Er3+. AB - Upon 976 nm diode laser excitation, the temperature dependence of the red upconversion emission of Er3+ in CaWO4:Yb3+/Er3+ phosphor was studied from 298 to 478 K. The spectrum was verified to consist of two Stark components originating from two Stark sublevels of 4F9/2 excited state to 4I15/2 ground state of Er3+. The valley-to-peak intensity ratio (VPR) of this double-peak spectrum was found to increase linearly with the rise of temperature. The maximum relative sensitivity of this VPR method was obtained to be about 0.20% K-1 at 298 K. Moreover, a study on the power dependence was also performed, suggesting that VPR method is immune to the pump power and is thus suitable for monitoring the temperature. PMID- 27410342 TI - Extended femtosecond laser wavelength range to 330 nm in a high power LBO based optical parametric oscillator. AB - We experimentally demonstrate a compact tunable, high average power femtosecond laser source in the ultraviolet (UV) regime. The laser source is based on intra cavity frequency doubling of a temperature-tuned lithium tribotate (LBO) optical parametric oscillator (OPO), synchronously pumped at 520 nm by a frequency doubled, Yb-fiber femtosecond laser amplifier system. By adjusting crystal temperature, the OPO can provide tunable visible to near-infrared (NIR) signal pulse, which have a wide spectral tuning range from 660 to 884 nm. Using a beta barium borate (BBO) crystal for intra-cavity frequency doubling, tunable femtosecond UV pulse are generated across 330~442 nm with up to 364 mW at 402 nm. PMID- 27410343 TI - Laser filamentation induced bubbles and their motion in water. AB - We demonstrate femtosecond filamentation induced convection in water by using a microscope directly observing the dynamic processes of the generated bubbles on a macroscopic time scale. The bubbles are driven by the filament in water and do directional movements. The angles between the bubbles' moving directions and the laser propagation direction varied at different positions along the filament, exhibiting a fusiform distribution. It indicates a fluid dynamic phenomenon depending on the local filament intensity, and reveals the convection processes induced by filamentation in water indirectly. PMID- 27410344 TI - Electrostrictive effect for active control of surface plasmon signals. AB - Real-time surface plasmon modulation was achieved by electrically varying the pitch of a nanoscale surface relief diffraction grating inscribed on an azobenzene thin film covered with a layer of silver. The azobenzene film was spin coated on an electrostrictive Lead Lanthanum Zirconate Titanate (PLZT) ceramic substrate and a combination of DC bias and AC electric fields were applied longitudinally on the PLZT ceramic causing a change in the grating's pitch as well as the surface plasmon's resonance wavelength. This method permits extremely accurate control of the surface plasmon wavelength for tunable optics applications. PMID- 27410345 TI - Indirect high-bandwidth stabilization of carrier-envelope phase of a high-energy, low-repetition-rate laser. AB - We demonstrate a method of stabilizing the carrier-envelope phase (CEP) of low repetition-rate, high-energy femtosecond laser systems such as TW-PW class lasers. A relatively weak high-repetition-rate (~1 kHz) reference pulse copropagates with a low-repetition-rate (10 Hz) high-energy pulse, which are s- and p-polarized, respectively. Using a Brewster angle window, the reference pulse is separated after the power amplifier and used for feedback to stabilize its CEP. The single-shot CEP of the high-energy pulse is indirectly stabilized to 550 mrad RMS, which is the highest CEP stability ever reported for a low-repetition rate (10-Hz) high-energy laser system. In this novel method, the feedback frequency of the reference pulse from the front-end preamplifier can be almost preserved. Thus, higher CEP stability can be realized than for lower frequencies. Of course, a reference pulse with an even higher repetition rate (e.g., 10 kHz) can be easily employed to sample and feed back CEP jitter over a broader frequency bandwidth. PMID- 27410346 TI - Performance evaluation of coherent free space optical communications with a double-stage fast-steering-mirror adaptive optics system depending on the Greenwood frequency. AB - The Greenwood frequency (GF) is influential in performance improvement for the coherent free space optical communications (CFSOC) system with a closed-loop adaptive optics (AO) unit. We analyze the impact of tilt and high-order aberrations on the mixing efficiency (ME) and bit-error-rate (BER) under different GF. The root-mean-square value (RMS) of the ME related to the RMS of the tilt aberrations, and the GF is derived to estimate the volatility of the ME. Furthermore, a numerical simulation is applied to verify the theoretical analysis, and an experimental correction system is designed with a double-stage fast-steering-mirror and a 97-element continuous surface deformable mirror. The conclusions of this paper provide a reference for designing the AO system for the CFSOC system. PMID- 27410347 TI - Use of weather research and forecasting model outputs to obtain near-surface refractive index structure constant over the ocean. AB - The methods to obtain atmospheric refractive index structure constant (Cn2) by instrument measurement are limited spatially and temporally and they are more difficult and expensive over the ocean. It is useful to forecast Cn2 effectively from Weather Research and Forecasting Model (WRF) outputs. This paper introduces a method that WRF Model is used to forecast the routine meteorological parameters firstly, and then Cn2 is calculated based on these parameters by the Bulk model from the Monin-Obukhov similarity theory (MOST) over the ocean near-surface. The corresponding Cn2 values measured by the micro-thermometer which is placed on the ship are compared with the ones forecasted by WRF model to determine how this method performs. The result shows that the forecasted Cn2 is consistent with the measured Cn2 in trend and the order of magnitude as a whole, as well as the correlation coefficient is up to 77.57%. This method can forecast some essential aspects of Cn2 and almost always captures the correct magnitude of Cn2, which experiences fluctuations of two orders of magnitude. Thus, it seems to be a feasible and meaningful method that using WRF model to forecast near-surface Cn2 value over the ocean. PMID- 27410348 TI - Sub-300 femtosecond soliton tunable fiber laser with all-anomalous dispersion passively mode locked by black phosphorus. AB - By using evanescent field optical deposition method, we had successfully fabricated an effective optoelectronic device based on multi-layer black phosphorus (BP), which is been heavily investigating 2 dimensional (2D) semiconducting material with similar structure as graphene and thickness dependent direct band-gap. By placing this BP-based optoelectronic device inside a highly compact all-anomalous dispersion fiber laser cavity, stable passive mode locking operation could be ensured and eventually a record 280 fs transmission limited soliton pulse with tunable central wavelength had been obtained through finely tailoring the cavity length. Other operation states, like bound soliton and noise-like state, had also been observed as well. This work demonstrates the enormous potential of BP for ultra-short pulse generation as an effective optoelectronic device. PMID- 27410349 TI - Influence of finite extinction ratio on performance of phase-sensitive optical time-domain reflectometry. AB - The leakage light of optical pulses due to finite extinction ratio (ER) of an electro-optic modulator (EOM) leads to Rayleigh backscattered noises over the entire fiber length, and limits spatial resolution and sensing range in phase sensitive optical time-domain reflectometry (Phi-OTDR). Two configurations are proposed to improve the ER of optical pulses for better spatial resolution over long sensing length. With ER of 55 dB using a nonlinear optical loop mirror, we achieved 2 m spatial resolution over 8.4 km sensing length; while with ER of 60 dB obtained by two cascaded EOMs, we can achieve a 1 m spatial resolution over the same range. Experimental results and analysis show that leakage of the optical pulses acts as a noise floor, which limits the highest spatial resolution over the same sensing range. PMID- 27410350 TI - Large aperture tunable-focus liquid lens using shape memory alloy spring. AB - A tunable-focus large aperture liquid lens is constructed using shape memory alloy (SMA) springs as actuators. The lens mainly consists of a shallow liquid filled cylindrical cavity bound by a thin compressible annular rim and encapsulated by a flexible circular membrane on the top of the rim and a rigid circular plate at the rim bottom. The lens optical power is adjusted by a controlled compression of the annular rim via actuation of the three shape-memory alloy (SMA) springs. Since the volume of the cavity liquid is constant, the rim compression bulges the flexible membrane outward thus reducing its radius of curvature and the lens focal length. The fabricated tunable lens demonstrated an optical power range of 0-4 diopters utilizing a driving voltage less than 3V. Lens optical wavefront profiling was done using a Shack-Hartmann sensor displaying a RMS wave front error of 0.77 um and 1.68 um at 0 D and + 4 D. The aperture diameter and thickness of the fabricated lens are 34 mm and 9 mm, respectively, while weighing 16.7 g. PMID- 27410351 TI - Extinction measurement with open-path cavity ring-down technique of variable cavity length. AB - Open-path cavity ring down (OPCRD) technique with variable cavity length was developed to measure optical extinction including scattering and absorption of air in laboratory environment at 635 nm wavelength. By moving the rear cavity mirror of the ring-down cavity to change cavity length, ring-down time with different cavity lengths was experimentally obtained and the dependence of total cavity loss on cavity length was determined. The extinction coefficient of air was determined by the slope of linear dependence of total cavity loss on cavity length. The extinction coefficients of air with different particle concentrations at 635 nm wavelength were measured to be from 10.46 to 84.19 Mm-1 (ppm/m) in a normal laboratory environment. This variable-cavity-length OPCRD technique can be used for absolute extinction measurement and real-time environmental monitoring without closed-path sample cells and background measurements. PMID- 27410352 TI - Experimental study of diode pumped rubidium amplifier for single higher-order Laguerre-Gaussian modes. AB - In this paper, we have set up a diode laser pumped rubidium amplifier for higher order Laguerre-Gauss (LG) modes. We experimentally realized amplification of higher-order LG modes including helical and sinusoidal LG03, LG13, LG23, and LG33 modes with their high purity held. This novel scheme of generating high-purity higher-order LG beams at high laser power is preferred to the second-generation gravitational wave interferometers. To the best of our knowledge, it is the first time this scheme is formulated. PMID- 27410353 TI - Designing the phase grating for Talbot-Lau phase-contrast imaging systems: a simulation and experiment study. AB - The performance of a Talbot-Lau interferometer depends to a great extent on its visibility. This means, to obtain high quality phase-contrast and dark-field images a high visibility is mandatory. Several parameters influence the visibility of such a system, like for example the x-ray spectrum, the inter grating distances or the parameters of the three gratings. In this multidimensional space, wave field simulations help to find the optimal combination of the grating specifications to construct a setup with a high visibility while retaining a fixed angular sensitivity. In this work we specifically analyzed the influence of the G1 grating duty cycle in simulations and experiments. We show that there is a lot of room for improvement by varying the duty cycle of the phase-shifting grating G1. As a result, by employing a third-integer duty cycle we can increase the visibility to up to 53 % in a laboratory setup with a polychromatic spectrum. The achieved visibility is more than two times higher compared to the result with a standard-type setup. This visibility gain allows a dose reduction by a factor of 5 preserving the same image quality. PMID- 27410354 TI - MEMS-based handheld scanning probe with pre-shaped input signals for distortion free images in Gabor-domain optical coherence microscopy. AB - High-speed scanning in optical coherence tomography (OCT) often comes with either compromises in image quality, the requirement for post-processing of the acquired images, or both. We report on distortion-free OCT volumetric imaging with a dual axis micro-electro-mechanical system (MEMS)-based handheld imaging probe. In the context of an imaging probe with optics located between the 2D MEMS and the sample, we report in this paper on how pre-shaped open-loop input signals with tailored non-linear parts were implemented in a custom control board and, unlike the sinusoidal signals typically used for MEMS, achieved real-time distortion free imaging without post-processing. The MEMS mirror was integrated into a compact, lightweight handheld probe. The MEMS scanner achieved a 12-fold reduction in volume and 17-fold reduction in weight over a previous dual-mirror galvanometer-based scanner. Distortion-free imaging with no post-processing with a Gabor-domain optical coherence microscope (GD-OCM) with 2 MUm axial and lateral resolutions over a field of view of 1 * 1 mm2 is demonstrated experimentally through volumetric images of a regular microscopic structure, an excised human cornea, and in vivo human skin. PMID- 27410355 TI - Visual encoder: robust and precise measurement method of rotation angle via high speed RGB vision. AB - In this paper, a new measurement method of the rotation angle of a rotor, which is named the 'visual encoder,' was proposed. This method is based on the principles of the vision-based method and the optical encoder, and realized by using a high-speed vision system. The visual encoder shows advantageous features such as non-contact, high-resolution and robustness against the free motion and the fluctuation of the rotation axis. A high resolution method to increase the measurement resolution was also suggested. The accuracy and the robustness of the visual encoder were confirmed through the experimental verifications, and the operation was possible at 6,000 rpm even under the fluctuation of rotation axis. PMID- 27410356 TI - Z-scan for thin media with more than one nonlocal nonlinear response. AB - A model to characterize the response of a thin media that can exhibit more than one nonlocal nonlinear response when it is illuminated with a Gaussian beam in a z-scan experiment is proposed. The model considers that these nonlocal contributions can be treated as independent contributions in the refractive or absorptive nonlinear response. Numerical results for two nonlocal nonlinear contributions with different magnitudes between them are presented. Experimental results obtained from a hydrogenated amorphous silicon sample are used to corroborate this model. PMID- 27410357 TI - Effect of heat treatments on the performance of polymer optical fiber sensor. AB - Although the numerous advantages of polymer optical fiber (POF) sensors have been applied in different fields, the measurement consistency and sensitivity of POF evanescent wave (EW) sensors are still affected by its thermal stability and water absorption. Therefore, we perform a study to demonstrate the mechanism of the effect of heat treatments on physical and optical properties of POF EW sensors. We investigate the surface morphology, composition, refractive index, geometry, and weight of the fiber-sensing region subjected to water and vacuum heat treatments. We examine the spectral transmission and transmitted light intensity of POF sensors. We present a theoretical investigation of the effect of heat treatments on the sensitivity of POF EW sensors. The performance of the prepared sensor is evaluated using glucose and Chlorella pyrenoidosa analytes. We discovered that the spectral transmission and transmitted light intensity of the fibers shows little effect of vacuum heat treatments. In particular, the sensors, which subject to vacuum heat treatment at 110 degrees C for 3 h, exhibit temperature-independent measuring consistency and high sensitivity in glucose solutions in the temperature range 15-60 degrees C and also show high sensitivity in Chlorella pyrenoidosa solutions. PMID- 27410358 TI - Sensitive determinations of Cu, Pb, Cd, and Cr elements in aqueous solutions using chemical replacement combined with surface-enhanced laser-induced breakdown spectroscopy. AB - In this study, chemical replacement combined with surface-enhanced laser-induced breakdown spectroscopy (CR-SENLIBS) was for the first time applied to improve the detection sensitivities of trace heavy metal elements in aqueous solutions. Utilizing chemical replacement effect, heavy metal ions in aqueous solution were enriched on the magnesium alloy surface as a solid replacement layer through reacting with the high chemical activity metallic magnesium (Mg) within 1 minute. Unitary and mixed solutions with Cu, Pb, Cd, and Cr elements were prepared to construct calibration curves, respectively. The CR-SENLIBS showed a much better detection sensitivity and accuracy for both unitary and mixed solutions. The coefficients of determination R2 of the calibration curves were above 0.96, and the LoDs were of the same order of magnitude, i.e., in the range of 0.016-0.386 MUg/mL for the unitary solution, and in the range of 0.025-0.420 MUg/mL for the mixed solution. These results show that CR-SENLIBS is a feasible method for improving the detection sensitivity of trace element in liquid sample, which definitely provides a way for wider application of LIBS in water quality monitoring. PMID- 27410359 TI - Experimental investigation of inter-core crosstalk tolerance of MIMO-OFDM/OQAM radio over multicore fiber system. AB - In this paper, the feasibility of space division multiplexing for optical wireless fronthaul systems is experimentally demonstrated by implementing high speed MIMO-OFDM/OQAM radio signals over 20km 7-core fiber and 0.4m wireless link. Moreover, the impact of optical inter-core crosstalk in multicore fibers on the proposed MIMO-OFDM/OQAM radio over fiber system is experimentally evaluated in both SISO and MIMO configurations for comparison. The experimental results show that the inter-core crosstalk tolerance of the proposed radio over fiber system can be relaxed to -10 dB by using the proposed MIMO-OFDM/OQAM processing. These results could guide high density multicore fiber design to support a large number of antenna modules and a higher density of radio-access points for potential applications in 5G cellular system. PMID- 27410360 TI - Static thermo-optic instability in double-pass fiber amplifiers. AB - A coupled-mode formalism, earlier used to describe transverse mode instabilities in single-pass optical fiber amplifiers is extended to the case of double-pass amplifiers. Contrary to the single-pass case, it is shown that the thermo-optic nonlinearity can couple light at the same frequency between the LP01 and LP11 modes, leading to a static deformation of the output beam profile. This novel phenomenon is caused by the interaction of light propagating in either direction with thermo-optic index perturbations caused by light propagating in the opposite direction. The threshold power for the static deformation is found to be several times lower than what is typically found for the dynamic modal instabilities observed in single-pass amplifiers. PMID- 27410361 TI - CAOS-CMOS camera. AB - Proposed and experimentally demonstrated is the CAOS-CMOS camera design that combines the coded access optical sensor (CAOS) imager platform with the CMOS multi-pixel optical sensor. The unique CAOS-CMOS camera engages the classic CMOS sensor light staring mode with the time-frequency-space agile pixel CAOS imager mode within one programmable optical unit to realize a high dynamic range imager for extreme light contrast conditions. The experimentally demonstrated CAOS-CMOS camera is built using a digital micromirror device, a silicon point-photo detector with a variable gain amplifier, and a silicon CMOS sensor with a maximum rated 51.3 dB dynamic range. White light imaging of three different brightness simultaneously viewed targets, that is not possible by the CMOS sensor, is achieved by the CAOS-CMOS camera demonstrating an 82.06 dB dynamic range. Applications for the camera include industrial machine vision, welding, laser analysis, automotive, night vision, surveillance and multispectral military systems. PMID- 27410362 TI - Electromechanically reconfigurable CdS nanoplate based nonlinear optical device. AB - Here, we report experimental demonstration of dynamic control and enhancement of second harmonic generation and two photon excited photoluminescence in CdS nanoplates via an electromechanically reconfigurable Fabry-Perot (FP) microcavity. Microcavity coupled CdS nanoplates can be configured as a single or dual wavelength nonlinear light source by tuning the pump wavelength while the output intensities can be tuned by the on-chip control voltage. Our work realizes a reconfigurable device platform with insight toward advanced optical devices based on semiconductor nanoplates for next generation on-chip tunable light sources, sensors and optomechanical systems. PMID- 27410363 TI - High power compatible internally sensed optical phased array. AB - The technical embodiment of the Huygens-Fresnel principle, an optical phased array (OPA) is an arrangement of optical emitters with relative phases controlled to create a desired beam profile after propagation. One important application of an OPA is coherent beam combining (CBC), which can be used to create beams of higher power than is possible with a single laser source, especially for narrow linewidth sources. Here we present an all-fiber architecture that stabilizes the relative output phase by inferring the relative path length differences between lasers using the small fraction of light that is back-reflected into the fiber at the OPA's glass-air interface, without the need for any external sampling optics. This architecture is compatible with high power continuous wave laser sources (e.g., fiber amplifiers) up to 100 W per channel. The high-power compatible internally sensed OPA was implemented experimentally using commercial 15 W fiber amplifiers, demonstrating an output RMS phase stability of lambda/194, and the ability to steer the beam at up to 10 kHz. PMID- 27410364 TI - Gradient-index design for mode conversion of diffracting beams. AB - Gradient-index (GRIN) media offer advantages over thin optical elements for beam shaping of strongly diffracting fields. A numerical GRIN design method is presented, where diffraction effects are considered in solving for the refractive index profile. The index profile is found by specifying a desired beam transformation throughout the GRIN volume and solving a series of phase retrieval problems. A Gaussian to flat-top beam shaper and a coherent beam combiner are shown as examples. Reduced beam distortion is demonstrated in comparison to a purely geometric design method. PMID- 27410365 TI - Silicon photonic time-wavelength pulse interleaver for photonic analog-to-digital converters. AB - A 4-channel time-wavelength optical pulse interleaver is implemented on a silicon chip. The interleaver forms a train of pulses with periodically changing wavelengths by demultiplexing the input pulse train into several wavelength components, delaying these components with respect to each other, and multiplexing them back into a single path. The interleaver is integrated on a silicon chip, with two arrays of microring resonator filters performing multiplexing and demultiplexing, and long sections of silicon waveguides acting as delay lines. The 4-channel interleaver is designed for an input pulse train with 1 GHz repetition rate, and is measured to have 0.35% RMS pulse timing error, insertion loss between 1.6 dB and 5.8 dB in different channels, crosstalk below 24 dB, and 52 nm free spectral range achieved using the Vernier effect. PMID- 27410366 TI - Design of chirped distributed Bragg reflector for octave-spanning frequency group velocity dispersion compensation in terahertz quantum cascade laser. AB - The strategies and approaches of designing chirped Distributed Bragg Reflector for group velocity compensation in metal-metal waveguide terahertz quantum cascade laser are investigated through 1D and 3D models. The results show the depth of the corrugation periods plays an important role on achieving broad-band group velocity compensation in terahertz range. However, the deep corrugation also brings distortion to the group delay behavior. A two-section chirped DBR is proposed to provide smoother group delay compensation while still maintain the broad frequency range (octave) operation within 2 THz to 4 THz. PMID- 27410367 TI - Stabilization of heterogeneous silicon lasers using Pound-Drever-Hall locking to Si3N4 ring resonators. AB - Recent results on heterogeneous Si/III-V lasers and ultra-high Q Si3N4 resonators are implemented in a Pound-Drever-Hall frequency stabilization system to yield narrow linewidth characteristics for a stable on-chip laser reference. The high frequency filtering is performed with Si resonant mirrors in the laser cavity. To suppress close in noise and frequency walk off, the laser is locked to an ultra-high Q Si3N4 resonator with a 30 million quality factor. The laser shows high frequency noise levels of 60 * 103 Hz2/Hz corresponding to 160 kHz linewidth, and the low frequency noise is suppressed 33 dB to 103 Hz2/Hz with the PDH system. PMID- 27410368 TI - Control of radiation angle by introducing symmetric end structure to oblique waveguide in three-dimensional photonic crystal. AB - We investigate the radiation angle of an oblique waveguide in a stripe-stacked three-dimensional photonic crystal. We show that the output-light is radiated in a different direction from the oblique waveguide direction. Moreover, the radiation polar angle varies from 30 degrees to 50 degrees depending on the frequency. To inhibit the frequency dependence and obtain vertical radiation, we introduced a symmetric structure at the end of the waveguide. As a result of cancellation of the in-plane asymmetric wavenumber, the radiation polar angle is less than 6 degrees from the surface-normal direction and does not depend on frequency. PMID- 27410369 TI - Temporally-stable active precision mount for large optics. AB - We present a temporally-stable active mount to compensate for manufacturing induced deformations of reflective optical components. In this paper, we introduce the design of the active mount, and its evaluation results for two sample mirrors: a quarter mirror of 115 * 105 * 9 mm3, and a full mirror of 228 * 210 * 9 mm3. The quarter mirror with 20 actuators shows a best wavefront error rms of 10 nm. Its installation position depending deformations are addressed by long-time measurements over 14 weeks indicating no significance of the orientation. Size-induced differences of the mount are studied by a full mirror with 80 manual actuators arranged in the same actuator pattern as the quarter mirror. This sample shows a wavefront error rms of (27+/ 2) nm over a measurement period of 46 days. We conclude that the developed mount is suitable to compensate for manufacturing-induced deformations of large reflective optics, and likely to be included in the overall systems alignment procedure. PMID- 27410370 TI - New vibration-assisted magnetic abrasive polishing (VAMAP) method for microstructured surface finishing. AB - In order to polish microstructured surface without deteriorating its profile, we propose a new vibration-assisted magnetic abrasive polishing (VAMAP) method. In this method, magnetic force guarantees that the magnetic abrasives can well contact the microstructured surface and access the corners of microstructures while vibration produces a relative movement between microstructures and magnetic abrasives. As the vibration direction is parallel to the microstructures, the profile of the microstructures will not be deteriorated. The relation between vibration and magnetic force was analyzed and the feasibility of this method was experimentally verified. The results show that after polishing, the surface finish around microstructures was significantly improved while the profile of microstructures was well maintained. PMID- 27410371 TI - Low-crosstalk operation of directly modulated DFB laser array TOSA for 112-Gbit/s application. AB - A directly modulated DFB laser (DML) array transmitter optical sub-assembly (TOSA) operating at 112 Gbit/s was fabricated for the first time. The DML array chip, which was integrated with a GND pad, and the DML array sub-assembly were designed to suppress the adjacent electrical crosstalk of the DML array TOSA. The 3-dB bandwidths of the fabricated TOSA exceeded 18 GHz. The electrical crosstalk of the TOSA was suppressed to less than -20 dB below 18GHz. Under simultaneous 4 channel 28-Gbit/s (112 Gbit/s) operation, the OTU4 mask margins were degraded by a maximum of only 6% compared with those under discrete operation. Error-free transmissions over a 10-km single-mode fiber were demonstrated for all the lanes under 112-Gbit/s operation. PMID- 27410372 TI - Design of practicable phase-change metadevices for near-infrared absorber and modulator applications. AB - Phase-change chalcogenide alloys, such as Ge2Sb2Te5 (GST), have very different optical properties in their amorphous and crystalline phases. The fact that such alloys can be switched, optically or electrically, between such phases rapidly and repeatedly means that they have much potential for applications as tunable photonic devices. Here we incorporate chalcogenide phase-change films into a metal-dielectric-metal metamaterial electromagnetic absorber structure and design absorbers and modulators for operation at technologically important near-infrared wavelengths, specifically 1550 nm. Our design not only exhibits excellent performance (e.g. a modulation depth of ~77% and an extinction ratio of ~20 dB) but also includes a suitable means for protecting the GST layer from environmental oxidation and is well-suited, as confirmed by electro-thermal and phase-transformation simulations, to in situ electrical switching. We also present a systematic study of design optimization, including the effects of expected manufacturing tolerances on device performance and, by means of a sensitivity analysis, identify the most critical design parameters. PMID- 27410373 TI - Quasinormal mode theory and design of on-chip single photon emitters in photonic crystal coupled-cavity waveguides. AB - Using a quasinormal mode (QNM) theory for open cavity systems, we present detailed calculations and designs of a photonic crystal nanocavity (PCN) side coupled to a photonic crystal waveguide (PCW) for on-chip single photon source applications. We investigate various cavity-waveguide geometries using an L3 PCN coupled to a W1 PCW, obtaining the quality factors, effective mode volumes, and single photon Purcell factors of the complete loaded cavity-waveguide system as a function of spatial separation between the two. We also show that the quality factor does not monotonically increase with increasing separation between the PCN and PCW, and we identify a particular hole/defect which acts as the key structural parameter in the cavity-waveguide coupling. PMID- 27410374 TI - Dark spots along slowly scaling chains of plasmonic nanoparticles. AB - We numerically investigate the optical response of slowly scaling linear chains of mismatched silver nanoparticles. Hybridized plasmon chain resonances manifest unusual local field distributions around the nanoparticles that result from symmetry breaking of the geometry. Importantly, we find localization patterns characterized by bright hot-spots alternated by what we term dark spots. A dark spot is associated to dark plasmons that have collinear and antiparallel dipole moments along the chain. As a result, the field amplification in the dark interjunction gap is extinguished for incident polarization parallel to the chain axis. Despite the strong plasmonic coupling, the nanoparticles on the sides of this dark gap experience a dramatic asymmetric field amplification with amplitude gain contrast > 2*102. Remarkably, also for polarization orthogonal to the axis, gap hot-spots form on resonance. PMID- 27410375 TI - Preparation of a nonlinear coherent state of the mechanical resonator in an optomechanical microcavity. AB - We propose a scheme for generation of a nonlinear coherent state (NCS) of a mechanical resonator (MR) in an optomechanical micro-cavity, in which a two-level quantum dot (QD) and the microcavity are respectively driven by a strong laser and a weak laser. This microcavity can be engineered within a photonic band-gap (PBG) material. By properly tuning the frequency of the weak driving field, two photon blockade phenomenon occurs. The QD-cavity subsystem can evolve into a dark state due to the damping of the microcavity and the elimination of the decay rate of the QD at selected frequencies in the PBG material. In this situation, the phonon mode of the MR can be prepared into a NCS, which is a non-classical state and possesses the sub-Poisson statistics. We also demonstrate the Wigner function of the NCS, which negativity implies its non-classicality. PMID- 27410376 TI - Strain-induced vibration and temperature sensing BOTDA system combined frequency sweeping and slope-assisted techniques. AB - A BOTDA sensing scheme combined frequency sweeping and slope-assisted techniques is proposed and experimentally demonstrated for simultaneously temperature and strain-induced vibration sensing. In this scheme, during sweeping Brillouin gain spectrum (BGS) for temperature measurement, we simultaneously perform FFT to the time-domain traces whose probe-pump frequency difference (PPFD) is within the FWHM of the BGS at each position of fiber, and the location and the frequency of the strain-induced vibration event can be acquired based on SA-BOTDA technique. In this way, the vibration can be continuously measured at each selected working frequency point during the BGS scanning process and multiple measurements of vibration event can be completed in one whole BGS scanning process. Meanwhile, double sidebands probe method is employed to reduce the nonlocal effects. In our experiment, a temperature event and two vibration events with the frequency of 7.00Hz or 10.00Hz are simultaneously measured near the end of 10.6km long sensing fiber in a traditional BOTDA system. The system shows 1.2 degrees C temperature accuracy and 0.67Hz frequency resolution, as well as a 3m spatial resolution. The proposed method may find some potential applications where both the strain induced vibration frequency and temperature are the diagnostic objects. PMID- 27410377 TI - Ultrathin flexible terahertz polarization converter based on metasurfaces. AB - We present a method to design and fabricate a kind of converters based on flexible metasurfaces which can change the polarization state of an incident terahertz beam. The metasurface consists of a two-dimensional array of rectangular metallic antennas that can abruptly change the phase of the incoming terahertz beam. Experimentally demonstrated half-wave plates generate 0.1 THz beam with a pi/2 polarization rotation. By slightly changing the structure of the converter, an elliptically or circularly polarized beam is expected to be obtained. These flexible terahertz converters may have many potential applications in terahertz technology. PMID- 27410378 TI - Efficient broadband highly dispersive HfO2/SiO2 multilayer mirror for pulse compression in near ultraviolet. AB - We report on design, production and implementation of a highly dispersive broadband dielectric multilayer mirror covering near ultraviolet range from 290 nm to 350 nm. The described mirrors, having 92% spectrally averaged reflectance in the ultraviolet range and ~ 85 fs of group delay difference, that allow compression to ~ 7 fs, provide a strong foundation for generation of few-fs pulses in the near ultraviolet. PMID- 27410379 TI - Handy method to calibrate division-of-amplitude polarimeters for the first three Stokes parameters. AB - This paper presents a complete and original calibration framework for the three CCD polarimetric cameras. These Division-of-Amplitude imaging polarimeters provide polarization images in real-time and open new applications in robotics. In order to fully exploit properties from polarization images, the sensor has to be calibrated leading sometimes to a tedious task that has to be undertaken with specific optical devices in a controlled environment. The proposed framework relies only on the use of a tablet and enables both to calibrate the geometric and the polarization settings of the camera. After rotating freely by hand the tablet in front of the camera, the system is automatically calibrated providing both the well-known geometric calibration matrix as well as the polarization calibration matrix. The last one is derived from the estimation of the orientation of the three polarizers, and the estimation of their relative values of degree of polarization and average transmittance. PMID- 27410380 TI - Integrating cavity based gas cells: a multibeam compensation scheme for pathlength variation. AB - We present a four beam ratiometric setup for an integrating sphere based gas cell, which can correct for changes in pathlength due to sphere wall contamination. This allows for the gas absorption coefficient to be determined continuously without needing to recalibrate the setup. We demonstrate the technique experimentally, measuring methane gas at 1651nm. For example, contamination covering 1.2% of the sphere wall resulted in an uncompensated error in gas absorption coefficient of ~41%. With the ratiometric scheme, this error was reduced to ~2%. Potential limitations of the technique, due to subsequent deviations from mathematical assumptions are discussed, including severe sphere window contamination. PMID- 27410381 TI - Hot electron generation by aluminum oligomers in plasmonic ultraviolet photodetectors. AB - We report on an integrated plasmonic ultraviolet (UV) photodetector composed of aluminum Fano-resonant heptamer nanoantennas deposited on a Gallium Nitride (GaN) active layer which is grown on a sapphire substrate to generate significant photocurrent via formation of hot electrons by nanoclusters upon the decay of nonequilibrium plasmons. Using the plasmon hybridization theory and finite difference time-domain (FDTD) method, it is shown that the generation of hot carriers by metallic clusters illuminated by UV beam leads to a large photocurrent. The induced Fano resonance (FR) minimum across the UV spectrum allows for noticeable enhancement in the absorption of optical power yielding a plasmonic UV photodetector with a high responsivity. It is also shown that varying the thickness of the oxide layer (Al2O3) around the nanodisks (tox) in a heptamer assembly adjusted the generated photocurrent and responsivity. The proposed plasmonic structure opens new horizons for designing and fabricating efficient opto-electronics devices with high gain and responsivity. PMID- 27410382 TI - Lens coupled tunable Young's double pinhole system for hard X-ray spatial coherence characterization. AB - We have implemented a modified Young's double slit experiment using pinholes with tunable separation distance coupled with compound refractive lens for hard X-ray spatial coherence characterization. Varying distance between the apertures provides a high sensitivity to the determination of spatial coherence across a wide range of experimental parameters. The use of refractive lenses as a Fourier transformer ensures far field registration conditions and allows the realization of a very compact experimental setup in comparison with the classical Young technique and its derivatives. The tunable double aperture interferometer was experimentally tested at the ESRF ID06 beamline in the energy range from 8 to 25 keV. The spatial coherence and the source size were measured by evaluating the visibility of the interference fringes at various separation distances between the apertures and this value agrees very well with the data obtained by other techniques. The proposed scheme can be used for comprehensive characterization of the coherence properties of the source on low emittance synchrotrons in the hard X-ray region. PMID- 27410383 TI - Performance comparison of acrylic and thiol-acrylic resins in two-photon polymerization. AB - Microfabrication by two-photon polymerization is investigated using resins based on thiol-ene chemistry. In particular, resins containing different amounts of a tetrafunctional acrylic monomer and a tetrafunctional thiol molecule are used to create complex microstructures. We observe the enhancement of several characteristics of two-photon polymerization when using thiol-acrylic resins. Specifically, microfabrication is carried out using higher writing velocities and it produces stronger polymeric microstructures. Furthermore, the amount of shrinkage typically observed in the production of three-dimensional microstructures is reduced also. By means of microspectrometry, we confirm that the thiol-acrylate mixture in TPP resins promote monomer conversion inducing a higher degree of cross-linked network formation. PMID- 27410384 TI - The Economic and Epidemiological Impact of Focusing Voluntary Medical Male Circumcision for HIV Prevention on Specific Age Groups and Regions in Tanzania. AB - BACKGROUND: Since its launch in 2010, the Tanzania National Voluntary Medical Male Circumcision (VMMC) Program has focused efforts on males ages 10-34 in 11 priority regions. Implementers have noted that over 70% of VMMC clients are between the ages of 10 and 19, raising questions about whether additional efforts would be required to recruit men age 20 and above. This analysis uses mathematical modeling to examine the economic and epidemiological consequences of scaling up VMMC among specific age groups and priority regions in Tanzania. METHODS AND FINDINGS: Analyses were conducted using the Decision Makers' Program Planning Tool Version 2.0 (DMPPT 2.0), a compartmental model implemented in Microsoft Excel 2010. The model was populated with population, mortality, and HIV incidence and prevalence projections from external sources, including outputs from Spectrum/AIDS Impact Module (AIM). A separate DMPPT 2.0 model was created for each of the 11 priority regions. Tanzania can achieve the most immediate impact on HIV incidence by circumcising males ages 20-34. This strategy would also require the fewest VMMCs for each HIV infection averted. Circumcising men ages 10-24 will have the greatest impact on HIV incidence over a 15-year period. The most cost-effective approach (lowest cost per HIV infection averted) targets men ages 15-34. The model shows the VMMC program is cost saving in all 11 priority regions. VMMC program cost-effectiveness varies across regions due to differences in projected HIV incidence, with the most cost-effective programs in Njombe and Iringa. CONCLUSIONS: The DMPPT 2.0 results reinforce Tanzania's current VMMC strategy, providing newfound confidence in investing in circumcising adolescents. Tanzanian policy makers and program implementers will continue to focus scale-up of VMMC on men ages 10-34 years, seeking to maximize program impact and cost-effectiveness while acknowledging trends in demand among the younger and older age groups. PMID- 27410385 TI - Factors for Assessing the Effectiveness of Early Rehabilitation after Minimally Invasive Total Knee Arthroplasty: A Prospective Cohort Study. AB - The effectiveness of current rehabilitation programs is supported by high-level evidence from the results of randomized controlled trials, but an increasing number of patients are not discharged from the hospital because of the schedule of the critical path (CP). The present study aimed to determine which factors can be used to assess the effectiveness of early rehabilitation. We enrolled 123 patients with medial knee osteoarthritis (OA) who had undergone unilateral minimally invasive total knee arthroplasty for the first time. The following factors were assessed preoperatively: the maximum isometric muscle strength of the knee extensors and flexors, maximum knee and hip joint angle, pain, 5-m maximum walking speed, sex, age, body mass index, exercise habits, Kellgren Lawrence grade, femorotibial angle, failure side (bilateral or unilateral knee OA), and functional independence measure. We re-evaluated physical function (i.e., muscle strength, joint angle, and pain) and motor function (5-m maximum walking speed) 14 days postoperatively. Changes in physical function, motor function (5-m maximum walking speed), and number of days to independent walking were used as explanatory variables. The postoperative duration of hospitalization (in days) was used as the dependent variable in multivariate analyses. These analyses were adjusted for sex, age, body mass index, exercise habits, Kellgren Lawrence grade, femorotibial angle, failure side, and functional independence measure. The duration of hospitalization was significantly affected by the number of days to independent walking (p < 0.001, beta = 0.507) and a change in the 5-m maximum walking speed (p = 0.016, beta = -0.262). Multiple regression analysis showed that the radiographic knee grade (p = 0.029, beta = 0.239) was a significant confounding factor. Independent walking and walking speed recovery were considered to reduce the duration of hospitalization. Therefore, these indices can be used to assess the effectiveness of early rehabilitation. PMID- 27410386 TI - EFSPI/PSI working group on data sharing: accessing and working with pharmaceutical clinical trial patient level datasets - a primer for academic researchers. AB - BACKGROUND: Access to patient level datasets from clinical trial sponsors continues to be an important topic for the Pharmaceutical Industry as well as academic institutions and researchers. How to make access to patient level data actually happen raises many questions from the perspective of the researcher. METHODS: Patient level data access models of all major pharmaceutical companies were surveyed and recommendations made to guide academic researchers in the most efficient way through the process of requesting and accessing patient level data. RESULTS: The key considerations for researchers covered here are finding information; writing a research proposal to request data access; the review process; how data are shared; and the expectations of the data holder. A lot of clinical trial information is available on public registries and so these are great sources of information. Depending on the research proposal the required information may be available in Clinical Study Reports and therefore patient level data may not need to be requested. Many data sharing systems have an electronic form or template but in cases where these are not available the proposal needs to be created as a stand-alone document outlining the purpose, statistical analysis plan, identifying the studies for which data are required, the research team members involved, any conflicts of interest and the funding for the research. There are three main review processes - namely having an internal review board, external review board selected by the data holder or an external review board selected by a third party. Data can be shared through Open access i.e. on a public website, direct sharing between the data holder and the researcher, controlled access or the data holder identifies a contract organization to access the data and perform the analyses on behalf of the researcher. The data that are shared will have accompanying documentation to assist the researcher in understanding the original clinical trial and data collection methods. The data holder will require a legally binding data sharing agreement to be set up with the researcher. Additionally the data holder may be available to provide some support to the researcher if questions arise. CONCLUSION: Whilst the benefits and value of patient level data sharing have yet to be fully realised, we hope that the information outlined in this article will encourage researchers to consider accessing and re-using clinical trial data to support their research questions. PMID- 27410387 TI - HIV Knowledge, Risk Behavior, Stigma, and Their Impact on HIV Testing among Asian American and Pacific Islanders: A Review of Literature. AB - Asian American and Pacific Islanders (AAPIs) are the fastest growing population in the United States with documented increases in HIV rates. AAPIs are as likely as other racial/ethnic groups to engage in HIV-related risk behaviors, while being concomitantly less likely to have been HIV tested. Testing is a critical step in HIV prevention. Research points to various barriers to HIV-related testing including HIV knowledge and attitude and stigma. However, these factors and their impact among AAPIs are poorly understood. Myths about this population's "model minority" status compound AAPIs' sociocultural factors including English language proficiency, access to healthcare, and a culture of "silence" that negatively influences HIV-related research. In this article, the authors review the scientific literature on knowledge, risk behavior, and stigma to document the current state of research. Based on the review the authors offer a set of research, policy, and practice recommendations for social workers and other service providers working with AAPIs. PMID- 27410388 TI - Simultaneous Two-Photon Absorption to Gerade Excited Singlet States of Diphenylacetylene and Diphenylbutadiyne Using Optical-Probing Photoacoustic Spectroscopy. AB - Simultaneous two-photon absorption to one-photon forbidden electronically excited states of diphenylacetylene (DPA) and diphenylbutadiyne (DPB) was investigated by means of highly sensitive optical-probing photoacoustic spectroscopy. The incident laser power dependencies on photoacoustic signal intensity indicate that the signals are dominated by the two-photon absorption regime. Two-photon absorption is responsible for transitions to gerade excited states based on the selection rule. The two-photon absorption bands observed in the heat action spectra were assigned with the aid of quantum chemical calculations. The relative magnitude of the two-photon absorption cross sections of DPA and DPB was estimated, and the larger two-photon absorption cross section of DPB was related to the resonance effect with the red-shifted one-photon allowed 1(1)B1u <- 1(1)Ag transition of DPB. PMID- 27410390 TI - The world of wounds comes together. PMID- 27410391 TI - Surgical wound dehiscence in an Australian community nursing service: time and cost to healing. AB - OBJECTIVE: Surgical wound dehiscence (SWD) increases the length of hospital stay and impacts on patient wellbeing and health-care costs. Globally, the health-care costs associated with SWD are poorly reported and those reported are frequently associated with surgical site infection (SSI), rather than dehiscence of non microbial cause. This retrospective study describes and reports on the costs and time to healing associated with a number of surgical patients who were referred to a community nursing service for treatment of an SWD following discharge from a metropolitan hospital, in Perth, Western Australia. METHOD: Descriptive statistical analysis was carried out to describe the patient, wound and treatment characteristics. A costing analysis was conducted to investigate the cost of healing these wounds. RESULTS: Among the 70 patients referred with a SWD, 55% were treated for an infected wound dehiscence which was a significant factor (p=0.001). Overall, the cost of treating the 70 patients with a SWD in a community nursing service was in excess of $56,000 Australian dollars (AUD) (L28,705) and did not include organisational overheads or travel costs for nurse visits. The management of infection contributed to 67% of the overall cost. CONCLUSION: SWD remains an unquantified aspect of wound care from a prevalence and fiscal point of view. Further work needs to be done in the identification of SWD and which patients may be 'at risk'. DECLARATION OF INTEREST: The authors declare they have no competing interests. PMID- 27410389 TI - Expression of Biphenyl Synthase Genes and Formation of Phytoalexin Compounds in Three Fire Blight-Infected Pyrus communis Cultivars. AB - Pear (Pyrus communis) is an economically important fruit crop. Drops in yield and even losses of whole plantations are caused by diseases, most importantly fire blight which is triggered by the bacterial pathogen Erwinia amylovora. In response to the infection, biphenyls and dibenzofurans are formed as phytoalexins, biosynthesis of which is initiated by biphenyl synthase (BIS). Two PcBIS transcripts were cloned from fire blight-infected leaves and the encoded enzymes were characterized regarding substrate specificities and kinetic parameters. Expression of PcBIS1 and PcBIS2 was studied in three pear cultivars after inoculation with E. amylovora. Both PcBIS1 and PcBIS2 were expressed in 'Harrow Sweet', while only PcBIS2 transcripts were detected in 'Alexander Lucas' and 'Conference'. Expression of the PcBIS genes was observed in both leaves and the transition zone of the stem; however, biphenyls and dibenzofurans were only detected in stems. The maximum phytoalexin level (~110 MUg/g dry weight) was observed in the transition zone of 'Harrow Sweet', whereas the concentrations were ten times lower in 'Conference' and not even detectable in 'Alexander Lucas'. In 'Harrow Sweet', the accumulation of the maximum phytoalexin level correlated with the halt of migration of the transition zone, whereby the residual part of the shoot survived. In contrast, the transition zones of 'Alexander Lucas' and 'Conference' advanced down to the rootstock, resulting in necrosis of the entire shoots. PMID- 27410392 TI - Pressure ulcer healing with an intensive nutrition intervention in an acute setting: a pilot randomised controlled trial. AB - OBJECTIVE: To investigate the feasibility of recruitment, retention, intervention delivery and outcome measurement in a nutritional intervention to promote pressure ulcer healing in an acute setting. METHOD: Some 50 tertiary hospital patients with stage II or greater pressure ulcer were randomised to receive either individualised nutritional care by a dietitian, including prescription of wound healing supplements; or standard nutritional care. Relevant nutritional and pressure ulcer (PU) parameters were collected at day 5, 10, 15, 22 and then weekly or until discharge. RESULTS: The median length of hospital stay was 14 days (1-70) with 29 patients discharged by day 15. There were 24 patients discharged before their PU fully healed. Per cent change in valid PU area and score measures from baseline to day 15 were chosen for outcome data analysis to account for varying initial size and severity of the wound and length of stay. There was a larger percentage reduction in PU measures in the intervention group, but this was not statistically significant. Little difference was found in nutritional intake between the control and intervention groups indicating a requirement to focus on effective delivery of the intervention in future studies. Future studies in the acute setting need to account for length of stay and ideally follow patients until full healing. CONCLUSION: Results indicate a positive association with nutrition intervention and PU healing and that a rigorously designed and adequately powered study is feasible. DECLARATION OF INTEREST: This research was supported by a grant from the Queensland Health, Health Practitioner Research Scheme. The authors have no conflicts of interest to declare. PMID- 27410393 TI - Platelet-rich plasma, bilayered acellular matrix grafting and negative pressure wound therapy in diabetic foot infection. AB - Management and treatment of acute severe diabetic foot disease in patients with suboptimal glycaemic control is a critical issue in wound repair. This paper discusses the clinical efficacy of an aggressive surgical intervention combined with targeted use of regenerative medical therapies in limb preservation. Negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), bilayered acellular matrix grafting and split-thickness skin grafting were combined to treat a patient with diabetes, foot necrotising fasciitis and gaseous gangrene. The wound was completely healed. The clinical outcome revealed that a multi intervention strategy could be effective for large necrotising fasciitis wounds. Early clinical observation, suggests aggresive surgical intervention preserving intact tissue and targeted use of new regenerative technologies can lead to preservation of a limb. DECLARATION OF INTEREST: The authors have received no financial support for the material presented in this study outside of the scope of standard patient care reimbursement. This work was supported by the National Natural Science Foundation of China (NO. 81500596) awarded to Dr Wuquan Deng. PMID- 27410394 TI - Cross-linked hyaluronic acid in pressure ulcer prevention. AB - OBJECTIVE: Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. METHOD: All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. RESULTS: There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus reducing the exogenous pressure stress: thus, the induction of a thick hydrophilic substrate supports adequate mesenchymal and blood cells traffic to immediately restore any early or impending damage to the skin. DECLARATION OF INTEREST: The authors certify that there is no conflict of interest with any financial organisation regarding the material discussed in the manuscript. PMID- 27410395 TI - Efficacy of a collagen-based dressing in an animal model of delayed wound healing. AB - OBJECTIVE: The aim of this study was to evaluate in vitro and in vivo the efficacy of GBT013, a collagen-based dressing, for the treatment of chronic wounds, in a db/db mouse model of diabetes. METHOD: Macroscopic and histologic analyses of db/db mice wound healing with GBT013 or saline gauze were assessed. The mRNA expression and the proliferation of dermal fibroblast were investigated. Matrix metalloproteinases (MMP)-2 and MMP-9 activities were quantified. RESULTS: In db/db mice, GBT013 improves wound epithelialisation when compared with saline gauze. Histological analysis of scar tissue also shows an enhancement of remodelling associated with no sign of acute inflammation. In addition, GBT013 significantly decreases interleukin (IL)-6 and IL-8, significantly increases tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 fibroblast mRNA expression and significantly reduces in vitro MMP-2 and MMP-9 enzymatic activities. Moreover, GBT013 allows cell growth inside the matrix and stimulates proliferation of human dermal fibroblast. CONCLUSION: By contributing to restore MMPs/TIMPs balance, GBT013 may function in all key stages of wound healing, such as inflammation, proliferation and tissue remodelling, and ultimately may provide a favourable environment for skin repair. DECLARATION OF INTEREST: This work was supported by Genbiotech, the R&D subsidiary of Laboratoires Genevrier, a pharmaceutical company. PMID- 27410396 TI - Mental Illness and Firearms Background Checks-Combatting Violence Without Inhibiting Care. PMID- 27410397 TI - KetoABNO/NOx Cocatalytic Aerobic Oxidation of Aldehydes to Carboxylic Acids and Access to alpha-Chiral Carboxylic Acids via Sequential Asymmetric Hydroformylation/Oxidation. AB - A method for aerobic oxidation of aldehydes to carboxylic acids has been developed using organic nitroxyl and NOx cocatalysts. KetoABNO (9 azabicyclo[3.3.1]nonan-3-one N-oxyl) and NaNO2 were identified as the optimal nitroxyl and NOx sources, respectively. The mildness of the reaction conditions enables sequential asymmetric hydroformylation of alkenes/aerobic aldehyde oxidation to access alpha-chiral carboxylic acids without racemization. The scope, utility, and limitations of the oxidation method are further evaluated with a series of achiral aldehydes bearing diverse functional groups. PMID- 27410398 TI - Fifteen years of Belgian experience with external quality assessment of semen analysis. AB - Semen analysis is difficult to standardize, quality control and quality assurance are necessary to ensure that results are accurate and precise. This Belgian EQA survey over a 15-year period, involving 121 laboratories, attempted to reduce interlaboratory variability and at the same time, encouraged participating laboratories to implement correct techniques as advised by the WHO. Over the total period, the median coefficient of variation (CV) for sperm count, irrespective of the method used was 19.2%, while using improved Neubauer chamber resulted in a significantly (p < 0.001) lower median CV (14.4%). The overall median CV for rapid progressive motility was high (37.1%), but progressive motility (15.1%) and total motility (13.8%) were acceptable. Sperm morphology revealed a large variability in 79.4% irrespective of the staining procedures or evaluation criteria used. Participation in the Belgian EQA is on voluntary basis. Both, participation and implementation of the correct techniques should be made mandatory for accreditation and benefit of patient treatment. The existing Belgian EQA program should now be harmonized with other existing EQA schemes in Europe. PMID- 27410399 TI - Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria. AB - BACKGROUND: Enteric hyperoxaluria (EH) occurs with a rate of 5-24% in patients with inflammatory bowel disease, ileal resection and modern bariatric surgery. The excessive absorption of calcium oxalate causes chronic kidney disease (CKD) in patients with EH. In the literature, a single experience was reported in combined intestine-kidney transplantation (CIKTx) in patients with CKD due to EH. METHODS: After a report of 2 successful cases of CIKTx in patients with EH and CKD, one was performed at our center in a 59-year-old Caucasian female who developed intestinal failure with total parenteral nutrition (TPN) dependence after a complication post-bariatric surgery. Before CIKTx, she underwent kidney transplantation alone (KTA) twice, which failed due to oxalate nephropathy. RESULTS: In July 2014, the patient underwent CIKTx and bilateral allograft nephrectomy to avoid EH and oxalate stone burden. The postoperative course was complicated with acute tubular necrosis due to the use of high pressors related to perioperative bleeding. The patient was discharged 79 days after CIKTx with a serum creatinine (sCr) of 1.2 mg/dl and free of TPN. Her sCr increased at 7 months and a renal biopsy showed oxalate nephropathy. SLC26A6 (oxalate transporter) staining was significantly diminished in native duodenum/rectum as well as in intestinal allograft compared to control. CONCLUSIONS: KTA in patients with CKD secondary to EH should not be recommended due to high risk of recurrence. Although other centers showed good long-term outcomes in CIKTx, our patient experienced recurrence of EH due to oxalate transporter defect, early kidney allograft dysfunction and prolonged antibiotic use. PMID- 27410400 TI - Polymorphism in Zintl Phases ACd4Pn3: Modulated Structures of NaCd4Pn3 with Pn = P, As. AB - NaCd4P3 and NaCd4As3 were synthesized via short-way transport using the corresponding elements and CdI2 as mineralizer. At room temperature, the two beta polymorphs adopt the RbCd4As3 structure type which has been recently reported for alkali metal (A)-d(10) transition metal (T)-pnictides (Pn). The title compounds crystallize rhombohedrally in space group R3m at room temperature and show reversible phase transitions to incommensurately modulated alpha-polymorphs at lower temperatures. The low-temperature phases are monoclinic and can be described in space group Cm(alpha0gamma)s with q vectors of q = (-0.04,0,0.34) for alpha-NaCd4P3 and q1 = (-0.02,0,0.34) for alpha-NaCd4As3. Thermal properties, Raman spectroscopy, and electronic structures have been determined. Both compounds are Zintl phases with band gaps of 1.05 eV for beta-NaCd4P3 and ~0.4 eV for beta-NaCd4As3. PMID- 27410401 TI - A Structurally and Functionally Common Unit in Testes and Ovaries of Medaka (Oryzias latipes), a Teleost Fish. AB - Testes and ovaries are structurally and functionally different organs, but they originate from the same gonadal primordium. Here, we propose how a tissue composed of germ cells and sox9b-expressing cells underlain by a basement membrane develops a functionally common unit that reserves sexually indifferent or unfixed germline stem cells in both the ovaries and testes of adult medaka. During testicular development, the unit expands and gives rise to lobules where germline stem cells continuously produce a tremendous amount of sperm, while the unit in the female becomes germinal cradles that represent niche areas for neo oogenesis. A recent finding in female foxl3 mutants demonstrates that the unit can also serve as the niche for germline stem cells continuously producing sperm in the ovary. We hypothesize that this unit in medaka might correspond to the medullary cords of the gonadal primordium in amniotes and that fragmentation of the medullary cords during ovarian development may be related to the absence of germline stem cells. PMID- 27410402 TI - Tuberculosis is always a possibility (even in the intensive care unit). PMID- 27410403 TI - Glutamine in critically ill patients: is it a fundamental nutritional supplement? PMID- 27410404 TI - Recruitment maneuvers for acute respiratory distress syndrome: the panorama in 2016. PMID- 27410405 TI - Factors associated with job and personal satisfaction in adult Brazilian intensivists. AB - OBJECTIVE: To evaluate job and personal satisfaction rates in physicians who work in adult intensive care units and to identify the factors associated with satisfaction. METHODS: A cross-sectional study performed with physicians who participated in two intensive medicine online discussion groups. A questionnaire designed to assess the physician's sociodemographic profile and job was available for both groups for 3 months. At the end of the questionnaire, the participants addressed their degrees of job and personal satisfaction using a Likert scale in which 1 represented "very dissatisfied" and 5 represented "very satisfied". The association between sociodemographic and job characteristics with job and personal satisfaction was evaluated. Variables independently associated with satisfaction were identified using a logistic regression model. RESULTS: The questionnaire was answered by 250 physicians, of which 137 (54.8%) declared they were satisfied with their jobs and 34 (13.5%) were very satisfied. None of the evaluated characteristics were independently associated with job satisfaction. Regarding personal satisfaction, 136 (54.4%) physicians reported being satisfied, and 48 (19.9%) reported being very satisfied. Job satisfaction (OR = 7.21; 95%CI 3.21 - 16.20) and working in a university hospital (OR = 3.24; 95%CI 1.29 - 8.15) were factors independently associated with the personal satisfaction of the participants. CONCLUSION: The participant physicians reported job and personal satisfaction with their work in intensive care. Job satisfaction and working in a university hospital were independently associated with greater personal satisfaction. PMID- 27410406 TI - Mobility decline in patients hospitalized in an intensive care unit. AB - OBJECTIVE: To evaluate the variation in mobility during hospitalization in an intensive care unit and its association with hospital mortality. METHODS: This prospective study was conducted in an intensive care unit. The inclusion criteria included patients admitted with an independence score of >= 4 for both bed-chair transfer and locomotion, with the score based on the Functional Independence Measure. Patients with cardiac arrest and/or those who died during hospitalization were excluded. To measure the loss of mobility, the value obtained at discharge was calculated and subtracted from the value obtained on admission, which was then divided by the admission score and recorded as a percentage. RESULTS: The comparison of these two variables indicated that the loss of mobility during hospitalization was 14.3% (p < 0.001). Loss of mobility was greater in patients hospitalized for more than 48 hours in the intensive care unit (p < 0.02) and in patients who used vasopressor drugs (p = 0.041). However, the comparison between subjects aged 60 years or older and those younger than 60 years indicated no significant differences in the loss of mobility (p = 0.332), reason for hospitalization (p = 0.265), SAPS 3 score (p = 0.224), use of mechanical ventilation (p = 0.117), or hospital mortality (p = 0.063). CONCLUSION: There was loss of mobility during hospitalization in the intensive care unit. This loss was greater in patients who were hospitalized for more than 48 hours and in those who used vasopressors; however, the causal and prognostic factors associated with this decline need to be elucidated. PMID- 27410407 TI - Insights about serum sodium behavior after 24 hours of continuous renal replacement therapy. AB - OBJECTIVE: The aim of this study was to investigate the clinical and laboratorial factors associated with serum sodium variation during continuous renal replacement therapy and to assess whether the perfect admixture formula could predict 24-hour sodium variation. METHODS: Thirty-six continuous renal replacement therapy sessions of 33 patients, in which the affluent prescription was unchanged during the first 24 hours, were retrieved from a prospective collected database and then analyzed. A mixed linear model was performed to investigate the factors associated with large serum sodium variations (>= 8mEq/L), and a Bland-Altman plot was generated to assess the agreement between the predicted and observed variations. RESULTS: In continuous renal replacement therapy 24-hour sessions, SAPS 3 (p = 0.022) and baseline hypernatremia (p = 0.023) were statistically significant predictors of serum sodium variations >= 8mEq/L in univariate analysis, but only hypernatremia demonstrated an independent association (beta = 0.429, p < 0.001). The perfect admixture formula for sodium prediction at 24 hours demonstrated poor agreement with the observed values. CONCLUSIONS: Hypernatremia at the time of continuous renal replacement therapy initiation is an important factor associated with clinically significant serum sodium variation. The use of 4% citrate or acid citrate dextrose - formula A 2.2% as anticoagulants was not associated with higher serum sodium variations. A mathematical prediction for the serum sodium concentration after 24 hours was not feasible. PMID- 27410408 TI - Communication of mechanically ventilated patients in intensive care units. AB - OBJECTIVE: The aim of this study was to translate and culturally and linguistically adapt the Ease of Communication Scale and to assess the level of communication difficulties for patients undergoing mechanical ventilation with orotracheal intubation, relating these difficulties to clinical and sociodemographic variables. METHODS: This study had three stages: (1) cultural and linguistic adaptation of the Ease of Communication Scale; (2) preliminary assessment of its psychometric properties; and (3) observational, descriptive correlational and cross-sectional study, conducted from March to August 2015, based on the Ease of Communication Scale - after extubation answers and clinical and sociodemographic variables of 31 adult patients who were extubated, clinically stable and admitted to five Portuguese intensive care units. RESULTS: Expert analysis showed high agreement on content (100%) and relevance (75%). The pretest scores showed a high acceptability regarding the completion of the instrument and its usefulness. The Ease of Communication Scale showed excellent internal consistency (0.951 Cronbach's alpha). The factor analysis explained approximately 81% of the total variance with two scale components. On average, the patients considered the communication experiences during intubation to be "quite hard" (2.99). No significant correlation was observed between the communication difficulties reported and the studied sociodemographic and clinical variables, except for the clinical variable "number of hours after extubation" (p < 0.05). CONCLUSION: This study translated and adapted the first assessment instrument of communication difficulties for mechanically ventilated patients in intensive care units into European Portuguese. The preliminary scale validation suggested high reliability. Patients undergoing mechanical ventilation reported that communication during intubation was "quite hard", and these communication difficulties apparently existed regardless of the presence of other clinical and/or sociodemographic variables. PMID- 27410409 TI - Non-aneurysmal spontaneous subarachnoid hemorrhage: perimesencephalic versus non perimesencephalic. AB - OBJECTIVE: To compare the clinical evolution of perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. METHODS: The study was conducted retrospectively in a tertiary hospital center in the north region of Portugal. Included patients had no identifiable cause for subarachnoid hemorrhage. Several epidemiologic, clinical and imaging aspects were statistically analyzed, taking into account the differences in perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. RESULTS: Sixty-two patients met the inclusion criteria (46.8% - perimesencephalic subarachnoid hemorrhage; 53.2% - non-perimesencephalic subarachnoid hemorrhage). Demographic and clinical background characteristics were similar in both groups. Complications were more frequent in patients with non-perimesencephalic subarachnoid hemorrhage - 84.8% of the patients had at least one complication versus 48.3% in perimesencephalic subarachnoid hemorrhage. Vasospasm, infection and hydrocephaly were the most common complications (each was detected more frequently in the non-perimesencephalic subarachnoid hemorrhage group than in perimesencephalic subarachnoid hemorrhage group). Two patients died, both had a non-perimesencephalic subarachnoid hemorrhage. The median inpatient time was longer in the non-perimesencephalic subarachnoid hemorrhage group (21 versus 14 days). No incidents of rebleeding were reported during the follow-up period (mean time of 15 +/- 10.3 months). CONCLUSION: Perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage are two different entities that have different clinical outcomes, namely in terms of complication rate and median inpatient time. The management of these patients should respect this difference to improve treatment and optimize health care resources. PMID- 27410410 TI - Drug incompatibilities in the adult intensive care unit of a university hospital. AB - OBJECTIVES: This study sought to identify the physical and chemical incompatibilities among the drugs administered intravenously to patients admitted to an adult intensive care unit. We also aimed to establish pharmaceutical guidelines for administering incompatible drugs. METHODS: This cross-sectional, prospective, and quantitative study was conducted from July to September 2015. Drug incompatibilities were identified based on an analysis of the patient prescriptions available in the hospital online management system. A pharmaceutical intervention was performed using the guidelines on the preparation and administration of incompatible drugs. Adherence to those guidelines was subsequently assessed among the nursing staff. RESULTS: A total of 100 prescriptions were analyzed; 68 were incompatible with the intravenous drugs prescribed. A total of 271 drug incompatibilities were found, averaging 4.0 +/- 3.3 incompatibilities per prescription. The most commonly found drug incompatibilities were between midazolam and hydrocortisone (8.9%), between cefepime and midazolam (5.2%), and between hydrocortisone and vancomycin (5.2%). The drugs most commonly involved in incompatibilities were midazolam, hydrocortisone, and vancomycin. The most common incompatibilities occurred when a drug was administered via continuous infusion and another was administered intermittently (50%). Of the 68 prescriptions that led to pharmaceutical guidelines, 45 (66.2%) were fully adhered to by the nursing staff. CONCLUSION: Patients under intensive care were subjected to a high rate of incompatibilities. Drug incompatibilities can be identified and eliminated by the pharmacist on the multidisciplinary team, thereby reducing undesirable effects among patients. PMID- 27410411 TI - Atrial natriuretic factor: is it responsible for hyponatremia and natriuresis in neurosurgery? AB - OBJECTIVE: To evaluate the presence of hyponatremia and natriuresis and their association with atrial natriuretic factor in neurosurgery patients. METHODS: The study included 30 patients who had been submitted to intracranial tumor resection and cerebral aneurism clipping. Both plasma and urinary sodium and plasma atrial natriuretic factor were measured during the preoperative and postoperative time periods. RESULTS: Hyponatremia was present in 63.33% of the patients, particularly on the first postoperative day. Natriuresis was present in 93.33% of the patients, particularly on the second postoperative day. Plasma atrial natriuretic factor was increased in 92.60% of the patients in at least one of the postoperative days; however, there was no statistically significant association between the atrial natriuretic factor and plasma sodium and between the atrial natriuretic factor and urinary sodium. CONCLUSION: Hyponatremia and natriuresis were present in most patients after neurosurgery; however, the atrial natriuretic factor cannot be considered to be directly responsible for these alterations in neurosurgery patients. Other natriuretic factors are likely to be involved. PMID- 27410412 TI - Thrombin activatable fibrinolysis inhibitor as a bleeding predictor in liver transplantation: a pilot observational study. AB - OBJECTIVE: To correlate the levels of thrombin activatable fibrinolysis inhibitor in the immediate postoperative period and at 24 hours postoperatively with the volume of intraoperative bleeding. METHODS: Twenty-one patients allocated immediately before (elective or emergency) liver transplantation were analyzed. Blood samples were collected for thrombin activatable fibrinolysis inhibitor analysis at three different time points: immediately before liver transplantation (preoperative thrombin activatable fibrinolysis inhibitor), immediately after the surgical procedure (immediate postoperative thrombin activatable fibrinolysis inhibitor), and 24 hours after surgery (thrombin activatable fibrinolysis inhibitor 24 hours after surgery). The primary outcome of the study was to correlate the preoperative and immediate postoperative levels of thrombin activatable fibrinolysis inhibitor with intraoperative blood loss. RESULTS: There was a correlation between the preoperative thrombin activatable fibrinolysis inhibitor levels and bleeding volume (rho = -0.469; p = 0.05) but no correlation between the immediate postoperative thrombin activatable fibrinolysis inhibitor and bleeding volume (rho = -0.062; p = 0.79). No variable included in the linear regression analysis (prehemoglobin, prefibrinogen and preoperative thrombin activatable fibrinolysis inhibitor) was a bleeding predictor. There was a similar trend in the variation between the levels of thrombin activatable fibrinolysis inhibitor at the three different time points and fibrinogen levels. Patients who died within 6 months (14.3%) showed decreased preoperative and immediate postoperative levels of thrombin activatable fibrinolysis compared with survivors (preoperative: 1.3 +/- 0.15 versus 2.55 +/- 0.53, p = 0.06; immediate postoperative: 1.2 +/- 0.15 versus 2.5 +/- 0.42, p = 0.007). CONCLUSION: There was a moderate correlation between preoperative thrombin activatable fibrinolysis inhibitor and intraoperative bleeding in liver transplantation patients, although the predictive role of this variable independent of other variables remains uncertain. Preoperative and immediate postoperative thrombin activatable fibrinolysis inhibitor levels may have a role in the survival prognosis of this population; however, this possibility requires confirmation in further studies with larger sample sizes. PMID- 27410413 TI - Hantavirus cardiopulmonary syndrome successfully treated with high-volume hemofiltration. AB - Hantavirus cardiopulmonary syndrome has a high mortality rate, and early connection to extracorporeal membrane oxygenation has been suggested to improve outcomes. We report the case of a patient with demonstrated Hantavirus cardiopulmonary syndrome and refractory shock who fulfilled the criteria for extracorporeal membrane oxygenation and responded successfully to high volume continuous hemofiltration. The implementation of high volume continuous hemofiltration along with protective ventilation reversed the shock within a few hours and may have prompted recovery. In patients with Hantavirus cardiopulmonary syndrome, a short course of high volume continuous hemofiltration may help differentiate patients who can be treated with conventional intensive care unit management from those who will require more complex therapies, such as extracorporeal membrane oxygenation. PMID- 27410415 TI - To: Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children. PMID- 27410414 TI - Ralstonia pickettii bacteremia in hemodialysis patients: a report of two cases. AB - Ralstonia pickettii is a low-virulence gram-negative bacillus that may be associated with infections related to health care and may cause bacteremia. Ralstonia pickettii bacteremia is uncommon but is related to the contamination of medical products, mainly in immunodepressed patients. We present two cases of patients on chronic hemodialysis with Ralstonia pickettii bacteremia linked to contamination of the dialysis water. Similar cases have been published with links to intravenous fluid administration, medication ampules, and the use of extracorporeal oxygenation membranes, among other factors. The detection of Ralstonia pickettii bacteremia should provoke suspicion and a search for contaminated medical products, fluids, and/or medications. PMID- 27410416 TI - Reply to: Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children. PMID- 27410417 TI - To: Measurement of intracranial pressure and short-term outcomes of patients with traumatic brain injury: a propensity-matched analysis. PMID- 27410418 TI - Reply to: Measurement of intracranial pressure and short-term outcomes of patients with traumatic brain injury: a propensity-matched analysis. PMID- 27410419 TI - To: Therapeutic hypothermia after cardiac arrest: outcome predictors. PMID- 27410420 TI - Reply to: Therapeutic hypothermia after cardiac arrest: outcome predictors. PMID- 27410421 TI - Reply to: Neurological outcome after cardiac arrest: cold and dark issues [editorial]. PMID- 27410422 TI - Evaluation of the Catalytic Contribution from a Positioned General Base in Ketosteroid Isomerase. AB - Proton transfer reactions are ubiquitous in enzymes and utilize active site residues as general acids and bases. Crystal structures and site-directed mutagenesis are routinely used to identify these residues, but assessment of their catalytic contribution remains a major challenge. In principle, effective molarity measurements, in which exogenous acids/bases rescue the reaction in mutants lacking these residues, can estimate these catalytic contributions. However, these exogenous moieties can be restricted in reactivity by steric hindrance or enhanced by binding interactions with nearby residues, thereby resulting in over- or underestimation of the catalytic contribution, respectively. With these challenges in mind, we investigated the catalytic contribution of an aspartate general base in ketosteroid isomerase (KSI) by exogenous rescue. In addition to removing the general base, we systematically mutated nearby residues and probed each mutant with a series of carboxylate bases of similar pKa but varying size. Our results underscore the need for extensive and multifaceted variation to assess and minimize steric and positioning effects and determine effective molarities that estimate catalytic contributions. We obtained consensus effective molarities of ~5 * 10(4) M for KSI from Comamonas testosteroni (tKSI) and ~10(3) M for KSI from Pseudomonas putida (pKSI). An X-ray crystal structure of a tKSI general base mutant showed no additional structural rearrangements, and double mutant cycles revealed similar contributions from an oxyanion hole mutation in the wild-type and base-rescued reactions, providing no indication of mutational effects extending beyond the general base site. Thus, the high effective molarities suggest a large catalytic contribution associated with the general base. A significant portion of this effect presumably arises from positioning of the base, but its large magnitude suggests the involvement of additional catalytic mechanisms as well. PMID- 27410423 TI - Construction of Thermophilic Xylanase and Its Structural Analysis. AB - The glycoside hydrolase family 11 xylanase has been utilized in a wide variety of industrial applications, from food processing to kraft pulp bleaching. Thermostability enhances the economic value of industrial enzymes by making them more robust. Recently, we determined the crystal structure of an endo-beta-1,4 xylanase (GH11) from mesophilic Talaromyces cellulolyticus, named XylC. Ligand free XylC exists to two conformations (open and closed forms). We found that the "closed" structure possessed an unstable region within the N-terminal region far from the active site. In this study, we designed the thermostable xylanase by the structure-based site-directed mutagenesis on the N-terminal region. In total, nine mutations (S35C, N44H, Y61M, T62C, N63L, D65P, N66G, T101P, and S102N) and an introduced disulfide bond of the enzyme contributed to the improvement in thermostability. By combining the mutations, we succeeded in constructing a mutant for which the melting temperature was partially additively increased by >20 degrees C (measured by differential scanning calorimetry) and the activity was additively enhanced at elevated temperatures, without loss of the original specific activity. The crystal structure of the most thermostable mutant was determined at 2.0 A resolution to elucidate the structural basis of thermostability. From the crystal structure of the mutant, it was revealed that the formation of a disulfide bond induces new C-C contacts and a conformational change in the N-terminus. The resulting induced conformational change in the N terminus is key for stabilizing this region and for constructing thermostable mutants without compromising the activity. PMID- 27410424 TI - Comparisons Between Staphylectomy and Tie-Forward Procedures in Combination with a Sternothyroideus Myotenectomy for the Treatment of Intermittent Dorsal Displacement of the Soft Palate: An Observational Study. AB - OBJECTIVE: To compare the performance of horses with intermittent dorsal displacement of the soft palate (IDDSP) treated surgically with a control group and to determine whether there was a difference in postoperative performance between horses treated with a staphylectomy or a tie-forward procedure. STUDY DESIGN: A retrospective observational study. ANIMALS: Swedish Warmblood trotting horses (Standardbreds) with endoscopically confirmed IDDSP (n=56) and control horses (n=48) with endoscopically normal upper airways tested using overground endoscopy identified from medical records. METHODS: Generalized estimating equations that accounted for repeated measurements were used to compare presurgery and postsurgery racing performance (speed, m/s) of IDDSP horses, and to compare their performance to control horses. Similarly, the effects of surgical procedure type on whether horses returned to racing, postsurgical speed, career race starts and earnings were evaluated. RESULTS: There was no significant difference in race speed between IDDSP and control horses at any time point. The percentage of horses racing postoperatively, the number of career races, and career earnings did not differ between staphylectomy treated and tie-forward treated horses, nor between IDDSP and control horses. CONCLUSION: In our study there was no difference in the postoperative outcomes between the two surgical techniques used to treat definitively diagnosed IDDSP. These results find no strong evidence to promote use of one technique over another in the treatment of this condition. PMID- 27410425 TI - Perioperative Feeding Approaches in Single Ventricle Infants: A Survey of 46 Centers. AB - Background Feeding dysfunction occurs commonly in infants with single ventricle heart disease and impacts growth and long-term outcomes. Little evidence exists to guide safe feeding in this population. This study surveyed centers participating in the National Pediatric Cardiology Quality Improvement Collaborative to assess prevailing feeding practices amongthose caring for single ventricle neonates. Methods Web-based survey of 56 pediatric cardiac surgical centers was conducted. Questions addressed peri-operative feeding approaches and responses were presented and analyzed descriptively. Results Of 56 centers, 46 (82%) completed a survey. Preoperative feeding was common in single ventricle infants (30/46; 65%), routes varied. Centers who did not feed infants preoperatively cited the risk of necrotizing enterocolitis (16/16; 100%), presence of umbilical artery catheter (12/16; 75%), and prostaglandin infusion (9/16; 56%) as main concerns. 67% of centers reported no specific vital sign thresholds for withholding enteral feedings. In the postoperative period, most centers used an "internal guideline" (21/46; 46%) or an "informal practice" (15/46; 33%) to determine feeding readiness. Approaches to findings were significantly different among centers. About 40% of centers did not send patients home with feeding tubes, and there was no clear consensus between preferred feeding tube modality at discharge. Conclusion Considerable variation exists in feeding practices for infants with single ventricle congenital heart disease among 46 centers participating in a quality improvement collaborative. Although most centers generally feed infants preoperatively, feeding practices remain center-specific. Variability continues in the immediate post-operative and interstage periods. Further opportunities exist for investigation, standardization and development of best-practice feeding guidelines. PMID- 27410426 TI - Are you able not to react to what you hear? Inhibition behavior measured with an auditory Go/NoGo paradigm. AB - In everyday life people have to attend to, react to, or inhibit reactions to visual and acoustic cues. These abilities are frequently measured with Go/NoGo tasks using visual stimuli. However, these abilities have rarely been examined with auditory cues. The aims of our study (N = 106) are to develop an auditory Go/NoGo paradigm and to describe brain-healthy participants' performance. We tested convergent validity of the auditory Go/NoGo paradigm by analyzing the correlations with other neuropsychological tasks assessing attentional control and executive functions. We also analyzed the ecological validity of the task by examining correlations of self-reported impulsivity. In the first step we found that the participants are able to differentiate correctly among several sounds and also to appropriately react or inhibit a certain reaction most of the times. Convergent validity was suggested by correlations between the auditory Go/NoGo paradigm and the Color Word Interference Test, Trail Making Test, and Modified Card Sorting Test. We did not find correlations with self-reported impulsivity. Overall, the auditory Go/NoGo paradigm may be used to assess attention and inhibition in the context of auditory stimuli. Future studies may adapt the auditory Go/NoGo paradigm with specific acoustic stimuli (e.g., sound of opening a bottle) in order to address cognitive biases in particular disorders (e.g., alcohol dependence). PMID- 27410427 TI - Resilience-Back to the Future. PMID- 27410428 TI - Predicting complications in partial nephrectomy for T1a tumours: does approach matter? AB - OBJECTIVES: To assess differences in complications after robot-assisted (RAPN) and open partial nephrectomy (OPN) among experienced surgeons. PATIENTS AND METHODS: We identified patients in our institutional review board-approved, prospectively maintained database who underwent OPN or RAPN for management of unifocal, T1a renal tumours at our institution between January 2011 and August 2015. The primary outcome measure was the rate of 30-day overall postoperative complications. Baseline patient factors, tumour characteristics and peri operative factors, including approach, were evaluated to assess the risk of complications. RESULTS: Patients who underwent OPN were found to have a higher rate of overall complications (30.3% vs 18.2%; P = 0.038), with wound complications accounting for the majority of these events (11.8% vs 1.8%; P < 0.001). Multivariable logistic regression analysis showed the open approach to be an independent predictor of overall complications (odds ratio 1.58, 95% confidence interval 1.03-2.43; P = 0.035). Major limitations of the study include its retrospective design and potential lack of generalizability. CONCLUSIONS: The open surgical approach predicts a higher rate of overall complications after partial nephrectomy for unifocal, T1a renal tumours. For experienced surgeons, the morbidity associated with nephron-sparing surgery may be incrementally improved using the robot-assisted approach. PMID- 27410429 TI - Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet. AB - Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg.kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID- 27410430 TI - Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. AB - As the beta-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of beta catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96+/-2.71/8.92+/ 0.95%, Tb.N. = 4.88+/-0.51/3.95+/-0.44/mm, Tb. Sp. = 0.20+/-0.02/0.26+/-0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45+/-0.72/89.12+/-0.56%) and both diaphyseal (0.19+/-0.01/0.17+/ 0.01mm) and metaphyseal (0.10+/-0.01/0.08+/-0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of beta-catenin against the effects of stress in males and partial protection against unloading in females. PMID- 27410433 TI - Summer in the Parks. PMID- 27410432 TI - Inhibition of Midkine Augments Osteoporotic Fracture Healing. AB - The heparin-binding growth and differentiation factor midkine (Mdk) is proposed to negatively regulate osteoblast activity and bone formation in the adult skeleton. As Mdk-deficient mice were protected from ovariectomy (OVX)-induced bone loss, this factor may also play a role in the pathogenesis of postmenopausal osteoporosis. We have previously demonstrated that Mdk negatively influences bone regeneration during fracture healing. Here, we investigated whether the inhibition of Mdk using an Mdk-antibody (Mdk-Ab) improves compromised bone healing in osteoporotic OVX-mice. Using a standardized femur osteotomy model, we demonstrated that Mdk serum levels were significantly enhanced after fracture in both non-OVX and OVX-mice, however, the increase was considerably greater in osteoporotic mice. Systemic treatment with the Mdk-Ab significantly improved bone healing in osteoporotic mice by increasing bone formation in the fracture callus. On the molecular level, we demonstrated that the OVX-induced reduction of the osteoanabolic beta-catenin signaling in the bony callus was abolished by Mdk-Ab treatment. Furthermore, the injection of the Mdk-Ab increased trabecular bone mass in the skeleton of the osteoporotic mice. These results implicate that antagonizing Mdk may be useful for the therapy of osteoporosis and osteoporotic fracture-healing complications. PMID- 27410434 TI - Letters. PMID- 27410431 TI - The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease. AB - In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE epsilon4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for epsilon4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE epsilon4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE epsilon4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient's APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient's APOE status is missing. PMID- 27410436 TI - Scanning sports. PMID- 27410435 TI - Coming in sportsmedicine. PMID- 27410439 TI - Save the Boston Marathon. PMID- 27410438 TI - What Future for ATVs? PMID- 27410437 TI - Brief reports. PMID- 27410440 TI - Patellalgia. AB - In brief: Knee pain relating to or arising from the patellofemoral articulation is common in athletes. While direct trauma can cause this pain, patellofemoral malalignment and/or tracking problems seem to be its major source. This paper reviews the functional anatomy of the patella and describes the diagnostic and treatment procedures recommended for investigating and treating this condition. Most patients improve after an initial course of conservative treatment. Proximal or distal realignment may be surgically performed in patients who don't respond to conservative treatment. Patellectomy leaves some weakness in the quadriceps and should be used only as a last resort. PMID- 27410441 TI - Beta-Blockade and Response to Exercise: Influence of Training. AB - In brief: Beta-blockers and exercise training are recommended for treating cardiovascular disease and hypertension, and researchers have tried to determine the interaction of these two treatment modalities. Data from four studies conducted on 93 subjects over the past five years show that beta-blockade exerts a differential effect on the exercise capacity of subjects of different levels of health and fitness: It increases the capacity of angina patients; decreases the capacity of highly trained, fit individuals; and has little or no effect on the capacity of healthy, untrained individuals. PMID- 27410442 TI - The Biomechanical Basis of Growth Plate Injuries. AB - In brief: Children are at high risk of growth plate injury, contrary to previous research data. Of 134 consecutive growth plate injuries seen at the University of Arizona Hospital in Tucson over a six-year period, 22% occurred in team sports and 20% in activities such as using playground equipment, horseback riding, roller and ice skating, skateboarding, and bicycling. The authors review clinically useful anatomical and biomechanical aspects of the growth plate and its injuries, reflecting their own research as well as other studies. They also discuss prevention and diagnosis of this common source of childhood injury. PMID- 27410443 TI - How I Manage Sunburn. AB - In brief: Many people suffer the agonies of sunburn, sometimes repeatedly. Acute sunburn, characterized by erythema, edema, and at times blister formation, usually peaks within 12 to 24 hours after exposure, gradually subsides, and is followed by hyperpigmentation and peeling. Chronic sun damage, which leads to dry, leathery, wrinkled skin, frequently results in the growth of precancerous actinic keratoses. If enough damage occurs, skin cancers may appear. These must be treated and removed. However, the best treatment for sunburn damage is prevention. PMID- 27410444 TI - Motivation: The Key to Fitness Compliance. AB - In brief: The reasons people say they exercise are to feel better, to have a beautiful body, to socialize, and to be more healthy. People see a lack of free time as the main obstacle to physical activity. However, data from three surveys show that the need is not for more time but for using time that is already available. The author concludes that participants need a carefully tailored system of incentives and rewards to sustain the exercise habit until the intrinsic rewards of fitness become obvious. PMID- 27410445 TI - Congenital Ureteropelvic Junction Obstruction: Abdominal Pain in Runners. AB - In brief: This paper discusses ureteropelvic junction obstruction and presents a case report of a young male athlete with a 13-year history of vague abdominal pain associated with long-distance running. Ureteropelvic junction obstruction was found to be the cause of his pain. A review of similar cases showed a significant number of patients with vague abdominal pain produced by ureteropelvic junction obstruction. While IVP is the standard for diagnosis, ultrasonography can be a useful screening test. The authors conclude that ureteropelvic junction obstruction should be considered for patients with abdominal pain. PMID- 27410446 TI - Difficulty in Diagnosing and Treating Deep Vein Thrombosis in a Competitive Basketball Player. AB - In brief: Deep vein thrombosis and pulmonary embolism in young athletes are rare. The authors report a case of deep vein thrombosis in a high school basketball player whose symptoms of sharp chest pains in his right side, shortness of breath, chills, and hemoptysis suggested pneumonia. The case demonstrates a need for early diagnosis and proper therapy. PMID- 27410447 TI - City Parks: Untapped Resource for Fitness. AB - Parks have almost everything it takes to provide affordable fitness programs that are close to home. What's missing? Qualified instructors. But a new group is working hard to respond to this need. PMID- 27410448 TI - Treating Thermal Injury: Disagreement Heats Up. AB - Runners increase the risk of becoming hypothermic or hyperthermic by not training in heat before a hot-weather race and by ignoring their body' a warning signs while running. And once thermal injury occurs, diagnosis and treatment may vary according to who is in charge of the medical tent; discrepancies can be fatal. PMID- 27410450 TI - The Difference Between Strength and Power. PMID- 27410451 TI - Bee Pollen: Living Up to its Hype? PMID- 27410452 TI - Strengthening Hip Abductors and Adductors. PMID- 27410454 TI - Abstracts at a glance. PMID- 27410456 TI - Biallelic mutations in CYP26B1: A differential diagnosis for Pfeiffer and Antley Bixler syndromes. AB - Recently, a newly identified autosomal recessive skeletal dysplasia was described characterized by calvarial abnormalities (including cranium bifidum, coronal, and lambdoid synostosis), oligodactyly, femoral bowing, narrow thorax, small pelvic bones, and radiohumeral synostosis. In the two families described, a more severe phenotype led to in utero lethality in three siblings while in a single patient in a second family the phenotype was sufficiently mild to allow survival to 5 months of age. The disorder is caused by biallelic missense mutations in CYP26B1, which encodes for a cytochrome P450 enzyme responsible for the catabolism of retinoic acid in a temporally and spatially restricted fashion during embryonic development. Here, we provide the third family affected by the disorder and the first affected individual to survive beyond infancy. This woman homozygous for c.1303G>A; p.(Gly435Ser) in CYP26B1, which was associated with multisutural synostosis, radiohumeral synostosis, normal bone mineral density, and apparent intellectual disability, a phenotype with significant similarities to Antley Bixler and Pfeiffer syndromes. (c) 2016 Wiley Periodicals, Inc. PMID- 27410457 TI - [Magnetic resonance imaging anatomy of the feline salivary glands]. AB - OBJECTIVE: The aim of the study was to define anatomical characteristics of feline salivary glands using magnetic resonance imaging (MRI) and to describe landmarks for their reliable identification. MATERIAL AND METHODS: Heads of 37 adult cats without signs of diseased salivary glands on clinical examination or history were examined. In cats included in the prospective part of the study, the MRI study was completed within one hour after euthanasia (n = 16). In the retrospective part, previously performed MRI studies were evaluated (n = 21). The prospective part of the study included the following standardized sequences: T2 weighted (T2W) turbo spin echo (TSE), T2W fat-suppressed TSE and proton density weighted (PDW) TSE images in a transverse plane as well as T1-weighted (T1W) fast field echo (FFE) in the transverse, sagittal and dorsal planes. In the retrospective part, T2W TSE and T1W TSE transverse images pre- and post-contrast were analyzed. Initially, identification and delineation of the salivary glands from surrounding tissue was assessed. Anatomical structures of the head were then identified and defined as landmarks. The dimensions of the glands were measured on T2W TSE images and the signal intensity in relation to that of fat and muscle was described using all sequences. RESULTS: In total, 95.9% of the parotid glands and 100% of the mandibular glands could be visualized on T1W TSE and FFE images and on T2W TSE images. Additionally, 93.3% of the zygomatic glands were identified on T2W TSE sequences and 82.5% on T1W TSE and FFE images. The ventral buccal glands could be demarcated in some sequences (T2W TSE: 51.4%, T1W TSE and FFE: 18.9%). Anatomical landmarks facilitated gland identification. Comparing the size of the salivary glands of both groups revealed differences of up to 2 mm. CONCLUSION: Both the large salivary glands (Glandula [Gl.]. parotis and Gl. mandibularis) and the small salivary glands (Gl. zygomatica and Gl. buccalis ventralis) of the cat can be reliably identified on MRI images. PMID- 27410458 TI - Rate of Homogenous Nucleation of Ice in Supercooled Water. AB - The homogeneous freezing of water is of fundamental importance to a number of fields, including that of cloud formation. However, there is considerable scatter in homogeneous nucleation rate coefficients reported in the literature. Using a cold stage droplet system designed to minimize uncertainties in temperature measurements, we examined the freezing of over 1500 pure water droplets with diameters between 4 and 24 MUm. Under the assumption that nucleation occurs within the bulk of the droplet, nucleation rate coefficients fall within the spread of literature data and are in good agreement with a subset of more recent measurements. To quantify the relative importance of surface and volume nucleation in our experiments, where droplets are supported by a hydrophobic surface and surrounded by oil, comparison of droplets with different surface area to volume ratios was performed. From our experiments it is shown that in droplets larger than 6 MUm diameter (between 234.6 and 236.5 K), nucleation in the interior is more important than nucleation at the surface. At smaller sizes we cannot rule out a significant contribution of surface nucleation, and in order to further constrain surface nucleation, experiments with smaller droplets are necessary. Nevertheless, in our experiments, it is dominantly volume nucleation controlling the observed nucleation rate. PMID- 27410460 TI - Surgical treatment of megaduodenum in familial visceral myopathy - report of a case and review of the literature. AB - INTRODUCTION: Familial visceral myopathy (VM) is a rare genetic disease that affects intestinal motility and results in pseudo-obstruction. Medical treatments can provide supportive measures but no curative treatment. CASE REPORT: A 20-year old male with known diagnosis of VM was referred to our Unit in May 2013 with recurrent episodes of vomiting and hospital admissions not responding to medical treatment. Pre-operative imaging showed megaduodenum with marked delayed transit and normal small and large bowel transit. He underwent an elective Roux-en-Y duodeno-jejunostomy. The post-operative course was uneventful with complete resolution of the symptoms with a 2 years follow-up. DISCUSSION: Due to the early age of presentation, VM affects patient both psychologically and physically. Surgical treatment of megaduodenum in visceral myopathy in the absence of motility disorder of the small bowel seems to achieve satisfactory symptomatic relief and could be considered in this rare cohort of patients. PMID- 27410459 TI - Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231. AB - Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 +/- 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 +/- 4.62 mg catechin/g extract) and strong DPPH* radical scavenging (IC50 = 27.81 MUg/mL) and metal chelation activity (IC50 = 80.20 MUg/mL). The stem aqueous extract showed the highest ABTS*+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 MUg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated. PMID- 27410461 TI - Getting to the heart of the matter: Role of Streptococcus mutans adhesin Cnm in systemic disease. PMID- 27410462 TI - Processivity of nucleic acid unwinding and translocation by helicases. AB - Helicases are a class of enzymes that use the chemical energy of NTP hydrolysis to drive mechanical processes such as translocation and nucleic acid (NA) strand separation. Besides the NA unwinding speed, another important factor for the helicase activity is the NA unwinding processivity. Here, we study the NA unwinding processivity with an analytical model that captures the phenomenology of the NA unwinding process. First, we study the processivity of the non hexameric helicase that can unwind NA efficiently in the form of a monomer and the processivity of the hexameric helicase that can unwind DNA effectively, providing quantitative explanations of the available single-molecule experimental data. Then, we study the processivity of the non-hexameric helicases, in particular UvrD, in the form of a dimer and compare with that in the form of a monomer. The available single-molecule and some biochemical data showing that while UvrD monomer is a highly processive single-stranded DNA translocase it is inactive in DNA unwinding, whereas other biochemical data showing that UvrD is active in both single-stranded DNA translocation and DNA unwinding in the form of a monomer can be explained quantitatively and consistently. In addition, the recent single-molecule data are also explained quantitatively showing that constraining the 2B subdomain in closed conformation by intramolecular cross linking can convert Rep monomer with a very poor DNA unwinding activity into a superhelicase that can unwind more than thousands of DNA base pairs processively, even against a large opposing force. Proteins 2016; 84:1590-1605. (c) 2016 Wiley Periodicals, Inc. PMID- 27410463 TI - Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches. AB - The enzyme members of the dipeptidyl peptidase 4 (DPP4) gene family have the very unusual capacity to cleave the post-proline bond to release dipeptides from the N terminus of peptide/protein substrates. DPP4 and related enzymes are current and potential therapeutic targets in the treatment of type II diabetes, inflammatory conditions and cancer. Despite this, the precise biological function of individual dipeptidyl peptidases (DPPs), other than DPP4, and knowledge of their in vivo substrates remains largely unknown. For many years, identification of physiological DPP substrates has been difficult due to limitations in the available tools. Now, with advances in mass spectrometry based approaches, we can discover DPP substrates on a system wide-scale. Application of these approaches has helped reveal some of the in vivo natural substrates of DPP8 and DPP9 and their unique biological roles. In this review, we provide a general overview of some tools and approaches available for protease substrate discovery and their applicability to the DPPs with a specific focus on DPP9 substrates. This review provides comment upon potential approaches for future substrate elucidation. PMID- 27410464 TI - IL-1 family cytokines in cancer immunity - a matter of life and death. AB - IL-1 cytokines constitute a family of biologically active proteins with pleiotropic function especially in immunity. Both protective as well as deleterious properties of individual IL-1 family cytokines in tumor biology have been described. The function of IL-1-family cytokines depends on the producing source, the present (inflammatory) microenvironment and N-terminal proteolytical processing. Each of these determinants is shaped by different modes of cell death. Here we summarize the properties of IL-1 family cytokines in tumor biology, and how they are modulated by cell death. PMID- 27410465 TI - Near-Infrared-Emitting BODIPY-trisDOTA(111) In as a Monomolecular Multifunctional Imaging Probe: From Synthesis to In Vivo Investigations. AB - A new generation of monomolecular imaging probes (MOMIP) based on a distyryl BODIPY (BODIPY=boron-dipyrromethene) coupled with three DOTA macrocycles has been prepared (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The MOMIP presents good fluorescence properties and is very stable in serum. The bimodal probe was conjugated to trastuzumab, and an optical in vivo study showed high accumulation of the imaging agent at the tumor site. (111) In radiometallation of the bioconjugate was performed in high radiochemical yield, highlighting the potential of this new BODIPY-chelators derivative as a bimodal imaging probe. PMID- 27410467 TI - Evaluation of tissue engineering products for the management of neuropathic diabetic foot ulcers: an interim analysis. AB - OBJECTIVE: The objective of this prospective, multicentre clinical study is to assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix (MSWM) (porcine urinary bladder derived extracellular matrix) compared with Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management of non-healing diabetic foot ulcers (DFUs). METHOD: A randomised, multicentre study was conducted at thirteen centers throughout the US. It was designed to evaluate the incidence of ulcer closure, rate of ulcer healing, wound characteristics, patient quality of life, cost-effectiveness, and recurrence. Those subjects whose DFUs decreased in size by <=30% or increased by <=50% during the standard of care (SOC) phase were randomised into the treatment phase of the study. The study evaluated complete wound closure by eight weeks with weekly device application. A two-week post treatment SOC phase followed the treatment phase for any wounds that did not heal by the end of eight weeks, and wound closure was also evaluated at the end of that period. Ulcer recurrence at 6 months post-treatment was evaluated in the subjects that showed wound healing by the end of the post-treatment SOC phase. Standard adjunctive therapy, including debridement, saline irrigation and foot off-loading, was provided to both arms during the four-week screening period, after which eligible subjects were randomised in a 1:1 ratio, to either the MatriStem (MS) or DG treatment arm. This study was developed to evaluate the hypothesis that the wound outcomes observed after wound management with MS were non-inferior to those of DG after eight weeks. The authors present the planned interim results of this study after one half of the projected enrolment was completed. RESULTS: There were 95 subjects consented and entered into the SOC four-week screening phase of the trial and 56 were randomised into the treatment phase. At the planned interim analysis, there was a significantly lower cost per subject and significant improvement in patient quality of life for the subjects treated with MS compared with those managed with DG. However, there was not a statistically significant difference found during the analysis of the interim data between the two study groups for rate of wound healing or number of subjects with complete wound closure. CONCLUSION: The data from this interim analysis show that MSMM and MSWM provide results for healing DFUs that are similar to the results obtained for DG at a significant quality of life and economic advantage. PMID- 27410469 TI - The revised pressure ulcer staging criteria: where are we going and why? PMID- 27410474 TI - Voluntary Medical Male Circumcision for HIV Prevention in Malawi: Modeling the Impact and Cost of Focusing the Program by Client Age and Geography. AB - BACKGROUND: In 2007, the World Health Organization (WHO) recommended scaling up voluntary medical male circumcision (VMMC) in priority countries with high HIV prevalence and low male circumcision (MC) prevalence. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), an estimated 5.8 million males had undergone VMMC by the end of 2013. Implementation experience has raised questions about the need to refocus VMMC programs on specific subpopulations for the greatest epidemiological impact and programmatic effectiveness. As Malawi prepared its national operational plan for VMMC, it sought to examine the impacts of focusing on specific subpopulations by age and region. METHODS: We used the Decision Makers' Program Planning Toolkit, Version 2.0, to study the impact of scaling up VMMC to different target populations of Malawi. National MC prevalence by age group from the 2010 Demographic and Health Survey was scaled according to the MC prevalence for each district and then halved, to adjust for over-reporting of circumcision. In-country stakeholders advised a VMMC unit cost of $100, based on implementation experience. We derived a cost of $451 per patient-year for antiretroviral therapy from costs collected as part of a strategic planning exercise previously conducted in- country by UNAIDS. RESULTS: Over a fifteen-year period, circumcising males ages 10-29 would avert 75% of HIV infections, and circumcising males ages 10-34 would avert 88% of infections, compared to the current strategy of circumcising males ages 15-49. The Ministry of Health's South West and South East health zones had the lowest cost per HIV infection averted. Moreover, VMMC met WHO's definition of cost-effectiveness (that is, the cost per disability-adjusted life-year [DALY] saved was less than three times the per capita gross domestic product) in all health zones except Central East. Comparing urban versus rural areas in the country, we found that circumcising men in urban areas would be both cost-effective and cost-saving, with a VMMC cost per DALY saved of $120 USD and with 15 years of VMMC implementation resulting in lifetime HIV treatment costs savings of $331 million USD. CONCLUSIONS: Based on the age analyses and programmatic experience, Malawi's VMMC operational plan focuses on males ages 10-34 in all districts in the South East and South West zones, as well as Lilongwe (an urban district in the Central zone). This plan covers 14 of the 28 districts in the country. PMID- 27410475 TI - Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse. AB - We previously identified Wiz in a mouse screen for epigenetic modifiers. Due to its known association with G9a/GLP, Wiz is generally considered a transcriptional repressor. Here, we provide evidence that it may also function as a transcriptional activator. Wiz levels are high in the brain, but its function and direct targets are unknown. ChIP-seq was performed in adult cerebellum and Wiz peaks were found at promoters and transcription factor CTCF binding sites. RNA seq in Wiz mutant mice identified genes differentially regulated in adult cerebellum and embryonic brain. In embryonic brain most decreased in expression and included clustered protocadherin genes. These also decreased in adult cerebellum and showed strong Wiz ChIP-seq enrichment. Because a precise pattern of protocadherin gene expression is required for neuronal development, behavioural tests were carried out on mutant mice, revealing an anxiety-like phenotype. This is the first evidence of a role for Wiz in neural function. PMID- 27410476 TI - Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions. AB - The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5beta and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule-stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules. PMID- 27410478 TI - Socioeconomic Differences in Informed Decisions About Down Syndrome Screening: A Systematic Review and Research Agenda. AB - Supporting pregnant women to make informed choices about Down syndrome screening is widely endorsed. We reviewed the literature on: (a) the association between socioeconomic position and informed choices and decision-making about Down syndrome screening, and (b) the possible mediating variables (e.g., health literacy, numeracy skills, behavioral and communication variables) that might explain the relationship. EMBASE, MEDLINE, PubMed, CINAHL, and PsycINFO were searched from January 1999 to September 2014. The methodological quality of studies was determined by predefined criteria regarding the research aims, study design, study population and setting, measurement tools, and statistical analysis. A total of 33 studies met the inclusion criteria. Women from lower socioeconomic groups experience greater difficulties making informed choices about Down syndrome screening compared to women from higher socioeconomic groups. Most studies focus on individual dimensions of informed decision-making rather than assessing elements in conjunction with one another. Few studies have explored why there are socioeconomic differences in women's ability to make informed screening decisions. Future work is needed to identify mediating variables in this pathway. Systematic evidence-based intervention development to improve communication, understanding, and decision-making about Down syndrome screening is needed to ensure that women have an equal opportunity to make an informed choice about screening regardless of their socioeconomic position. PMID- 27410477 TI - The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer. AB - ER-targeted therapeutics provide valuable treatment options for patients with ER+ breast cancer, however, current relapse and mortality rates emphasize the need for improved therapeutic strategies. The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance of advanced tumors on ERalpha signaling, and provides a strong rationale for continued targeting of ERalpha. Here we describe GDC-0810, a novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was identified by prospectively optimizing ERalpha degradation, antagonism and pharmacokinetic properties. GDC 0810 induces a distinct ERalpha conformation, relative to that induced by currently approved therapeutics, suggesting a unique mechanism of action. GDC 0810 has robust in vitro and in vivo activity against a variety of human breast cancer cell lines and patient derived xenografts, including a tamoxifen-resistant model and those that harbor ERalpha mutations. GDC-0810 is currently being evaluated in Phase II clinical studies in women with ER+ breast cancer. PMID- 27410479 TI - Synthesis and biological activities of d-chiro-inositol analogues with insulin like actions. AB - d-chiro-inositol (DCI, 1) evokes therapeutic actions in diabetes and insulin resistance but has sub-optimal pharmacokinetic profiles. To investigate what positions on the DCI cyclohexanol ring may be amenable to modification to improve pharmaceutical formulations, a series of analogues based on DCI were synthesised. These compounds were then evaluated for their ability to stimulate glucose transport using 3T3-L1 adipocytes as a model system. Positional analyses indicate that the hydroxyl group at position 1 is not essential for activity and can be modified without affecting glucose uptake. Removal of the hydroxyl at position 3 also had minimal effect on activity but this group is sensitive to modification. By comparison, the oxygen at position 2 is crucial to the potency of DCI, although this group can withstand modification without fundamentally affecting activity. These data reveal that positions 1 and 2 on the cyclohexanol ring of DCI offer further scope for modification to develop DCI analogues with desirable pharmacokinetic profiles for the potential treatment of metabolic disease. PMID- 27410481 TI - ERRATUM. AB - [This corrects the article DOI: 10.1016/S0377-1237(08)80155-4.][This corrects the article DOI: 10.1016/S0377-1237(08)80146-3.]. PMID- 27410480 TI - Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. AB - Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-alpha concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. PMID- 27410482 TI - Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease. AB - BACKGROUND: The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer's ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. METHODS: 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. RESULTS: 33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer's ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer's ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. CONCLUSIONS: Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets. PMID- 27410484 TI - National Academies Hit the Brakes on Gene Drive-Modified Organisms. PMID- 27410483 TI - Data sharing and the evolving role of statisticians. AB - BACKGROUND: Greater transparency and, in particular, sharing of clinical study reports and patient level data for further research is an increasingly important topic for the pharmaceutical and biotechnology industry and other organisations who sponsor and conduct clinical research as well as academic researchers and patient advocacy groups. Statisticians are ambassadors for data sharing and are central to its success. They play an integral role in data sharing discussions within their companies and also externally helping to shape policy and processes while providing input into practical solutions to aid data sharing. Data sharing is generating changes in the required profile for statisticians in the pharmaceutical and biotechnology industry, as well as academic institutions and patient advocacy groups. DISCUSSION: Successful statisticians need to possess many qualities required in today's pharmaceutical environment such as collaboration, diplomacy, written and oral skills and an ability to be responsive; they are also knowledgeable when debating strategy and analytical techniques. However, increasing data transparency will require statisticians to evolve and learn new skills and behaviours during their career which may not have been an accepted part of the traditional role. Statisticians will move from being the gate-keepers of data to be data facilitators. To adapt successfully to this new environment, the role of the statistician is likely to be broader, including defining new responsibilities that lie beyond the boundaries of the traditional role. Statisticians should understand how data transparency can benefit them and the potential strategic advantage it can bring and be fully aware of the pharmaceutical and biotechnology industry commitments to data transparency and the policies within their company or research institute in addition to focusing on reviewing requests and provisioning data. Data transparency will evolve the role of statisticians within the pharmaceutical and biotechnology industry, academia and research bodies to a level which may not have been an accepted part of their traditional role or career. In the future, skills will be required to manage challenges arising from data sharing; statisticians will need strong scientific and statistical guiding principles for reanalysis and supplementary analyses based on researchers' requests, have enhanced consultancy skills, in particular the ability to defend good statistical practice in the face of criticism and the ability to critique methods of analysis. Statisticians will also require expertise in data privacy regulations, data redaction and anonymisation and be able to assess the probability of re-identification, an ability to understand analyses conducted by researchers and recognise why such analyses may propose different results compared to the original analyses. Bringing these skills to the implementation of data sharing and interpretation of the results will help to maximise the value of shared data while guarding against misleading conclusions. PMID- 27410485 TI - On-Surface Domino Reactions: Glaser Coupling and Dehydrogenative Coupling of a Biscarboxylic Acid To Form Polymeric Bisacylperoxides. AB - Herein we report the on-surface oxidative homocoupling of 6,6'-(1,4-buta-1,3 diynyl)bis(2-naphthoic acid) (BDNA) via bisacylperoxide formation on different Au substrates. By using this unprecedented dehydrogenative polymerization of a biscarboxylic acid, linear poly-BDNA with a chain length of over 100 nm was prepared. It is shown that the monomer BDNA can be prepared in situ at the surface via on-surface Glaser coupling of 6-ethynyl-2-naphthoic acid (ENA). Under the Glaser coupling conditions, BDNA directly undergoes polymerization to give the polymeric peroxide (poly-BDNA) representing a first example of an on-surface domino reaction. It is shown that the reaction outcome varies as a function of surface topography (Au(111) or Au(100)) and also of the surface coverage, to give branched polymers, linear polymers, or 2D metal-organic networks. PMID- 27410486 TI - Chemical Space Mapping and Structure-Activity Analysis of the ChEMBL Antiviral Compound Set. AB - Curation, standardization and data fusion of the antiviral information present in the ChEMBL public database led to the definition of a robust data set, providing an association of antiviral compounds to seven broadly defined antiviral activity classes. Generative topographic mapping (GTM) subjected to evolutionary tuning was then used to produce maps of the antiviral chemical space, providing an optimal separation of compound families associated with the different antiviral classes. The ability to pinpoint the specific spots occupied (responsibility patterns) on a map by various classes of antiviral compounds opened the way for a GTM-supported search for privileged structural motifs, typical for each antiviral class. The privileged locations of antiviral classes were analyzed in order to highlight underlying privileged common structural motifs. Unlike in classical medicinal chemistry, where privileged structures are, almost always, predefined scaffolds, privileged structural motif detection based on GTM responsibility patterns has the decisive advantage of being able to automatically capture the nature ("resolution detail"-scaffold, detailed substructure, pharmacophore pattern, etc.) of the relevant structural motifs. Responsibility patterns were found to represent underlying structural motifs of various natures-from very fuzzy (groups of various "interchangeable" similar scaffolds), to the classical scenario in medicinal chemistry (underlying motif actually being the scaffold), to very precisely defined motifs (specifically substituted scaffolds). PMID- 27410487 TI - The Role of Membrane Fluidization in the Gel-Assisted Formation of Giant Polymersomes. AB - Polymersomes are being widely explored as synthetic analogs of lipid vesicles based on their enhanced stability and potential uses in a wide variety of applications in (e.g., drug delivery, cell analogs, etc.). Controlled formation of giant polymersomes for use in membrane studies and cell mimetic systems, however, is currently limited by low-yield production methodologies. Here, we describe for the first time, how the size distribution of giant poly(ethylene glycol)-poly(butadiene) (PEO-PBD) polymersomes formed by gel-assisted rehydration may be controlled based on membrane fluidization. We first show that the average diameter and size distribution of PEO-PBD polymersomes may be readily increased by increasing the temperature of the rehydration solution. Further, we describe a correlative relationship between polymersome size and membrane fluidization through the addition of sucrose during rehydration, enabling the formation of PEO PBD polymersomes with a range of diameters, including giant-sized vesicles (>100 MUm). This correlative relationship suggests that sucrose may function as a small molecule fluidizer during rehydration, enhancing polymer diffusivity during formation and increasing polymersome size. Overall the ability to easily regulate the size of PEO-PBD polymersomes based on membrane fluidity, either through temperature or fluidizers, has broadly applicability in areas including targeted therapeutic delivery and synthetic biology. PMID- 27410489 TI - Selective H/D Exchange at Vinyl and Methylidene Groups with D2O Catalyzed by an Iridium Complex. AB - Selective H/D exchange at vinyl and methylidene groups of alkenes with D2O was promoted by an iridium catalyst generated in situ from a hydroxoiridium complex and N-mesylbenzamide. PMID- 27410488 TI - Hepcidin independent iron recycling in a mouse model of beta-thalassaemia intermedia. AB - In conditions such as beta-thalassaemia, stimulated erythropoiesis can reduce the expression of the iron regulatory hormone hepcidin, increasing both macrophage iron release and intestinal iron absorption and leading to iron loading. However, in certain conditions, sustained elevation of erythropoiesis can occur without an increase in body iron load. To investigate this in more detail, we made use of a novel mouse strain (RBC14), which exhibits mild beta-thalassaemia intermedia with minimal iron loading. We compared iron homeostasis in RBC14 mice to that of Hbbth3/+ mice, a more severe model of beta-thalassaemia intermedia. Both mouse strains showed a decrease in plasma iron half-life, although the changes were less severe in RBC14 mice. Despite this, intestinal ferroportin and serum hepcidin levels were unaltered in RBC14 mice. In contrast, Hbbth3/+ mice exhibited reduced serum hepcidin and increased intestinal ferroportin. However, splenic ferroportin levels were increased in both mouse strains. These data suggest that in low-grade chronic haemolytic anaemia, such as that seen in RBC14 mice, the increased erythroid iron requirements can be met through enhanced macrophage iron release without the need to increase iron absorption, implying that hepcidin is not the sole regulator of macrophage iron release in vivo. PMID- 27410490 TI - Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients. AB - ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half-life with increasing doses, consistent with target-mediated disposition. The apparent bioavailability was 36.3%-56.7% across single subcutaneous doses. Sixteen RA patients (n = 8/treatment) on stable methotrexate received 3 * 3.0 mg/kg subcutaneously every 4 weeks or every 2 weeks. Similar to single-dose treatment, ASP2408 concentrations peaked 2 to 3 days postdose, with a median t1/2 of approximately 8 days. Using CD86 receptor occupancy (RO) as a mechanistic biomarker, ASP2408 demonstrated dose-dependent binding to its target. ASP2408 3.0 mg/kg subcutaneously every 4 weeks and every 2 weeks led to a mean %CD86 RO >= 74.7% and >= 81.5%, respectively, within each dosing interval. ASP2408 was well tolerated across studies with no evidence of dose-limiting toxicity or clinically significant changes in clinical laboratory test results, vital signs, or 12-lead electrocardiograms. ASP2408 elicited antidrug antibodies in the majority of patients, but with no clinical sequelae. PMID- 27410491 TI - Rewiring the solid tumor epigenome for cancer therapy. AB - INTRODUCTION: Whereas tumorigenic processes have traditionally been attributed to gene amplification, deletion, or mutation, it is now clear that epigenetic changes represent an additional hallmark of cancer. This review explains the basic principles of epigenetic regulation and therapy, provides an overview of clinically approved drugs, introduces novel targets and compounds, and discusses the potential reasons behind treatment success and failure. AREAS COVERED: We provide a brief introduction to the concept of epigenetic regulation in general and explain how epigenetic pathways are altered in cancer. Based on this, we go on to explore the rational behind epigenetic cancer therapy, provide an overview of clinical success and failure of specific drugs, describe novel pharmaceutical targets, review epigenetic combination treatment, and finally discuss biological concepts influencing treatment success. Expert commentary: Even though many early epigenetic therapy trials had disappointing results, lessons learned from these studies have heavily influenced the design of modern trials leading to improved therapeutic outcomes. Better preclinical model systems may help to reduce the risk of clinical failure and to identify high-confidence targets for clinical follow-up. PMID- 27410492 TI - Post-coordination backbone functionalization of an imidazol-2-ylidene and its application to synthesize heteropolymetallic complexes incorporating the ambidentate IMes(CO2(-)) ligand. AB - Backbone functionalization of the pre-coordinated, emblematic IMes ligand with the COOH moiety was achieved upon treatment of Cp(CO)2Mn(IMes) with n-BuLi followed by CO2 and HCl to afford Cp(CO)2Mn(IMes(COOH)). The latter reacts with (1,10-phen)M(OAc)2 (M = Cu, Zn) to obtain M3Mn4 polymetallic complexes exhibiting the ambidentate IMes(CO2(-)) moiety as a key structural unit. PMID- 27410494 TI - HIV Testing Among Black and Hispanic Immigrants in the United States. AB - Late presentation is common among black and Hispanic US immigrants living with HIV. Little is known about HIV testing in this population because data are aggregated into racial and ethnic categories without regard to nativity. This study was undertaken to determine HIV testing patterns in these populations. We used data from the National Health Interview Survey (2007-2010), a nationally representative source of HIV testing data disaggregated by nativity. The sample consisted of 10,397 immigrants (83.9% Hispanic white, 13.1% non-Hispanic black, and 3.0% Hispanic black). The majority of participants were from the Caribbean, Central America, and Mexico (81.5%). Hispanic white immigrants were least likely to have undergone testing compared with non-Hispanic and Hispanic black immigrants (46.7% vs. 70.5% and 65.8%). Among immigrants with known risk factors or prior STDs, 59.2% and 74.8% reported previous HIV testing. Immigrants who had not recently talked to a healthcare provider were less likely to report testing: Hispanic white (AOR 0.65, 95% CI 0.58-0.72), non-Hispanic black (AOR 0.64, 95% CI 0.48-0.85), and Hispanic black (AOR 0.26, 95% CI 0.14-0.48). Only 17.2% of all immigrants intended to undergo HIV testing in the 12 months following participation in the survey. Among all three racial and ethnic groups, immigrants who reported a history of prior STDs were more likely to intend to test for HIV in the future. Many black and Hispanic immigrants to the United States have not undergone HIV testing. Interventions to increase access to HIV testing and awareness of transmission risk should be developed. PMID- 27410493 TI - Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment. AB - In the last three decades, extensive research on human immunodeficiency virus (HIV) has highlighted its capability to exploit a variety of strategies to enter and infect immune cells. Although CD4(+) T cells are well known as the major HIV target, with infection occurring through the canonical combination of the cluster of differentiation 4 (CD4) receptor and either the C-C chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4) coreceptors, HIV has also been found to enter other important immune cell types such as macrophages, dendritic cells, Langerhans cells, B cells, and granulocytes. Interestingly, the expression of distinct cellular cofactors partially regulates the rate in which HIV infects each distinct cell type. Furthermore, HIV can benefit from the acquisition of new proteins incorporated into its envelope during budding events. While several publications have investigated details of how HIV manipulates particular cell types or subtypes, an up-to-date comprehensive review on HIV tropism for different immune cells is lacking. Therefore, this review is meant to focus on the different receptors, coreceptors, and cofactors that HIV exploits to enter particular immune cells. Additionally, prophylactic approaches that have targeted particular molecules associated with HIV entry and infection of different immune cells will be discussed. Unveiling the underlying cellular receptors and cofactors that lead to HIV preference for specific immune cell populations is crucial in identifying novel preventative/therapeutic targets for comprehensive strategies to eliminate viral infection. PMID- 27410495 TI - Parenting Among Adolescents and Young Adults with Human Immunodeficiency Virus Infection in the United States: Challenges, Unmet Needs, and Opportunities. AB - Given the realistic expectations of HIV-infected adolescents and young adults (AYA) to have children and start families, steps must be taken to ensure that youth are prepared to deal with the challenges associated with their HIV and parenting. Literature reviews were conducted to identify published research and practice guidelines addressing parenting or becoming parents among HIV-infected AYA in the United States. Research articles or practice guidelines on this topic were not identified. Given the paucity of information available on this topic, this article provides a framework for the development of appropriate interventions and guidelines for use in clinical and community-based settings. First, the social, economic, and sexual and reproductive health challenges facing HIV-infected AYA in the United States are summarized. Next, family planning considerations, including age-appropriate disclosure of HIV status to those who are perinatally infected, and contraceptive and preconception counseling are described. The impact of early childbearing on young parents is discussed and considerations are outlined during the preconception, antenatal, and postnatal periods with regard to antiretroviral medications and clinical care guidelines. The importance of transitioning AYA from pediatric or adolescent to adult centered medical care is highlighted. Finally, a comprehensive approach is suggested that addresses not only medical needs but also emphasizes ways to mitigate the impact of social and economic factors on the health and well-being of these young parents and their children. PMID- 27410497 TI - Adolescent Human Immunodeficiency Virus Care Providers' Attitudes Toward the Use of Oral Pre-Exposure Prophylaxis in Youth. AB - Oral pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention is currently indicated for use in adults in the United States and may soon be indicated for minor adolescents. However, implementation of PrEP use among minors may present unique barriers. We conducted 15 individual, semi structured interviews among US clinicians caring for HIV-infected and at-risk youth. The theory-driven interview guide assessed demographics, perceived role of oral PrEP in HIV prevention among adolescents, perceived barriers to and facilitating factors for use of PrEP in adolescents, and clinician-reported likelihood of prescribing PrEP. Transcripts were analyzed using framework analysis. Overall, clinicians viewed PrEP as a time-limited intervention that is one part of a comprehensive approach to HIV prevention among adolescents. Perceived barriers to prescribing to minors included concerns about: confidentiality, legality of minors consenting to PrEP without parental involvement, ability of minors to understand the risks/benefits of PrEP, the possible impact of PrEP on bone accrual, off-label use of PrEP medication in minors, and the high costs associated with PrEP use. Clinician-reported facilitating factors for prescribing PrEP to youth included educating communities and other clinicians about PrEP, ensuring adequate financial resources and infrastructure for delivering PrEP, developing formal guidance on effective behavioral interventions that should be delivered with PrEP, and gaining personal experience with prescribing PrEP. Clinicians indicated greater comfort with prescribing PrEP to adults versus minors. For PrEP to become more widely available to youth at risk for HIV infection, barriers that are unique to PrEP use in minors must be addressed. PMID- 27410496 TI - Predictors and Profiles of Antiretroviral Therapy Adherence Among African American Adolescents and Young Adult Males Living with HIV. AB - Adherence to antiretroviral therapy (ART) is crucial for thwarting HIV disease progression and reducing secondary HIV transmission, yet youth living with HIV (YLH) struggle with adherence. The highest rates of new HIV infections in the United States occur in young African American men. A sample of 387 HIV-positive young African American males on ART was selected from a cross-sectional assessment of (YLH) receiving medical care within the Adolescent Trials Network for HIV/AIDS Interventions (ATN) from 2010 to 2012 (12-24 years old, median 22.00, SD 2.08). Participants completed self-reported adherence, demographic, health, and psychosocial measures. Sixty-two percent self-reported 100% ART adherence. Optimal data analysis identified frequency of cannabis use during the past 3 months as the strongest independent predictor of adherence, yielding moderate effect strength sensitivity (ESS) = 27.1, p < 0.001. Among participants with infrequent cannabis use, 72% reported full adherence; in contrast, only 45% of participants who used cannabis frequently reported full adherence. Classification tree analysis (CTA) was utilized to improve classification accuracy and to identify the pathways of ART adherence and nonadherence. The CTA model evidenced a 38% improvement above chance for correctly classifying participants as ART adherent or nonadherent. Participants most likely to be adherent were those with low psychological distress and minimal alcohol use (82% were adherent). Participants least likely to be adherent were those with higher psychological distress and engaged in weekly cannabis use (69% were nonadherent). Findings suggest multiple profiles of ART adherence for young African American males living with HIV and argue for targeted psychosocial interventions. PMID- 27410499 TI - Correction to: AIDS Patient Care and STDs 2016;30:247-253; DOI: 10.1089/apc.2016.0068. PMID- 27410500 TI - Introduction: Coronary Care. PMID- 27410498 TI - "She Told Them, Oh That Bitch Got AIDS": Experiences of Multilevel HIV/AIDS Related Stigma Among African American Women Living with HIV/AIDS in the South. AB - African American women bear a disproportionate burden of HIV/AIDS in the United States. Although they constitute only 13% of the US population, African Americans account for nearly 65% of all new HIV infections among American women. In addition, this population suffers comparatively greater adverse health outcomes related to HIV status. African American women living with HIV in the South may be further burdened by HIV/AIDS stigma, which is comparatively more pronounced in this region. To further explore this burden, we used narrative data and the Social Ecological Model to explore how African American women living with HIV in the US South recount, conceptualize, and cope with HIV/AIDS stigma at interpersonal, community, and institutional levels. Our narrative analysis suggests that HIV-positive African American women living in the South are vulnerable to experiences of multilevel HIV stigma in various settings and contexts across multiple domains of life. Stigma subsequently complicated disclosure decisions and made it difficult for women to feel supported in particular social, professional and medical settings that are generally regarded as safe spaces for noninfected individuals. Findings suggest that the debilitating and compounded effect of multilevel HIV/AIDS stigma on HIV-positive African American women in the South warrants closer examination to tailor approaches that effectively address the unique needs of this population. PMID- 27410501 TI - Prodromes in Myocardial Infarction and Unstable Angina. PMID- 27410503 TI - Major Coronary Risk Factors Before and After Myocardial Infarction. PMID- 27410502 TI - Long-Term Management of Complicated Myocardial Infarction. PMID- 27410504 TI - The Meaning of Lipid Profiles. PMID- 27410505 TI - The Psychologic Reactions of Patients in the Pre- and Post-Hospital Phases of Myocardial Infarction. PMID- 27410506 TI - The Contribution of Regular Physical Activity to the Ambulatory Care of Cardiac Patients. PMID- 27410507 TI - Exercise Testing and Training in Relation to Myocardial Infarction. PMID- 27410508 TI - Surgery in the Treatment of Coronary Artery Disease. PMID- 27410509 TI - The Surveillance of Patients with Implanted Cardiac Pacemakers. PMID- 27410510 TI - Summary Self-Test Coronary Care. PMID- 27410512 TI - Therapeutic Index To Advertisers. PMID- 27410511 TI - Summary Self-Test. PMID- 27410513 TI - Identification and Molecular Interaction Studies of Thyroid Hormone Receptor Disruptors among Household Dust Contaminants. AB - Thyroid hormone disrupting chemicals (THDCs), often found abundantly in the environment, interfere with normal thyroid hormone signaling and induce physiological malfunctions, possibly by affecting thyroid hormone receptors (THRs). Indoor dust ingestion is a significant human exposure route of THDCs, raising serious concerns for human health. Here, we developed a virtual screening protocol based on an ensemble of X-ray crystallographic structures of human THRbeta1 and the generalized Born solvation model to identify potential THDCs targeting the human THRbeta1 isoform. The protocol was applied to virtually screen an in-house indoor dust contaminant inventory, yielding 31 dust contaminants as potential THRbeta1 binders. Five predicted binders and one negative control were tested using isothermal titration calorimetry, of which four, i.e., 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), bisphenol A (3-chloro-2 hydroxypropyl) (2,3-dihydroxypropyl) ether (BADGE-HCl-H2O), 2,2',4,4' tetrahydroxybenzophenone (BP2), and 2,4-dichlorophenoxyacetic acid (2,4-D), were identified as THRbeta1 binders with binding affinities ranging between 60 MUM and 460 MUM. Molecular dynamics (MD) simulations were employed to examine potential binding modes of these binders and provided a rationale for explaining their specific recognition by THRbeta1. The combination of in vitro binding affinity measurements and MD simulations allowed identification of four new potential THR targeting THDCs that have been found in household dust. We suggest using the developed structure-based virtual screening protocol to identify and prioritize testing of potential THDCs. PMID- 27410514 TI - Old and new approaches to the interpretation of acid-base metabolism, starting from historical data applied to diabetic acidosis. AB - The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance. PMID- 27410515 TI - An inquiry into self-identification with retirement. AB - The aim of this qualitative study was to explore patterns in self-identification with being retired using deductive thematic analysis informed by the life course perspective. For this study, a set of women who self-identified as retired (n = 60) were asked to describe their current work status, major career interruptions, and factors that marked their retirement. This study provides important insights into the heterogeneity in women's retirement including a subset of individuals who self-identified as retired, not based on their own work force transitions but on that of their spouse or peers. Findings highlight the importance of recognizing that the construction of retirement identity can be context driven, varied, and subjective. PMID- 27410516 TI - Serum Neutralization Assay for the Determination of Antibody Levels Against Non Polio Enterovirus Strains in Central and Western Greece. AB - Mutations and recombination events have been identified in enteroviruses. Point mutations accumulate with a frequency of 6.3 * 10(-4) per base pair per replication cycle affecting the fitness, the circulation, and the infectivity of enteroviral strains. In the present report, the serological status of the Central and Western Greek population (Larissa and Ioannina, respectively) in the 1-10 year, 11-20-year, 21-30-year, and 31-40-year age groups against six non-polio enterovirus strains, their respective echovirus prototypes, and Sabin 1, 2, and 3 vaccine strains was evaluated, through serum-neutralization assay. In the Western Greek population, antibody levels were detected only for clinical isolates of E30 serotype in all age groups, and for environmental isolate LR61G3 (E6 serotype) only in the 31-40 age group, whereas an immunity level was observed in the Central Greek population, against all strains, except for EIS6B (E3 serotype). Amino acid substitutions were encountered across the structural region of the capsid, between the prototypes and the respective isolates. These substitutions may alter the antigenicity of each strain and may explain the variations observed in the neutralization titers of the different strains. As a consequence, these substitutions severely affect antibody binding and increase the ability of the virus to escape the immune response. It is tempting to assume that changes in the antigenic properties observed in circulating echoviruses represent a selection of viral variants that are less prone to be neutralized by human antibodies. These facts argue for the need of immunological studies to the population to avoid epidemics due to the circulation of highly evolved derivatives. PMID- 27410517 TI - Carrier Transport Enhancement in Conjugated Polymers through Interfacial Self Assembly of Solution-State Aggregates. AB - We demonstrate that local and long-range orders of poly(3-hexylthiophene) (P3HT) semicrystalline films can be synergistically improved by combining chemical functionalization of the substrate with solution-state disentanglement and preaggregation of P3HT in a theta solvent, leading to a very significant enhancement of the field effect carrier mobility. The preaggregation and surface functionalization effects combine to enhance the carrier mobility nearly 100-fold as compared with standard film preparation by spin-coating, and nearly 10-fold increase over the benefits of preaggregation alone. In situ quartz crystal microbalance with dissipation (QCM-D) experiments reveal enhanced deposition of preaggregates on surfaces modified with an alkyl-terminated self-assembled monolayer (SAM) in comparison to unaggregated polymer chains in the same conditions. Additional measurements reveal the combined preaggregation and surface functionalization significantly enhances local order of the conjugated polymer through planarization and extension of the conjugated backbone of the polymer which clearly translate to significant improvements of carrier transport at the semiconductor-dielectric interface in organic thin film transistors. This study points to opportunities in combining complementary routes, such as well known preaggregation with substrate chemical functionalization, to enhance the polymer self-assembly and improve its interfacial order with benefits for transport properties. PMID- 27410518 TI - Moral Fiber: Breakfast as a Symbol of 'a Good Start' in an Australian Obesity Intervention. AB - What are the symbolic meanings of breakfast in the context of one of Australia's largest childhood obesity intervention programs? Utilizing a range of theoretical insights into the morality of food and eating and the anthropology of food, we trace how breakfast is packaged and promoted to families in an Australian community as a 'healthy start' to the day. Through ethnographic and historic investigation, we argue that eating breakfast and certain types of breakfast foods are symbolic of a classed, healthy lifestyle pattern, embodying parental knowledge and bodily regulation to routinely structure daily life. In communities where poverty and unemployment are harsh realities, well-intentioned programs that encourage people to eat a healthy breakfast are encoded with an assemblage of moral values-of knowledge, foods, families, and times and spaces-that are often difficult to reconcile with the wider sociocultural context in which many people live. PMID- 27410519 TI - HDAC inhibitors with PD-1 blockade: a promising strategy for treatment of multiple cancer types? PMID- 27410520 TI - Metabolomics in Diabetic Kidney Disease: Unraveling the Biochemistry of a Silent Killer. AB - The development of new therapies for chronic diseases, such as diabetic kidney disease (DKD), will continue to be hampered by lack of sufficient biomarkers that will provide insights and will be responsive to treatment interventions. The recent application of metabolomic technologies, such as nuclear magnetic resonance and mass spectroscopy, has allowed large-scale analysis of small molecules to be interrogated in a targeted or untargeted manner. Recent advances from both human and animal studies that have arisen from metabolomic analysis have recognized that mitochondrial function and fatty acid oxidation play key roles in the development and progression of DKD. Although many challenges in the technology for clinical chronic kidney disease (CKD) are yet to be validated, there will very likely be ongoing major contributions of metabolomics to develop new biochemical understanding for diabetic and CKD. The clinical application of metabolomics and accompanying bioinformatic tools will likely be a cornerstone of personalized medicine triumphs for CKD. PMID- 27410521 TI - Contextual Positive Coping as a Factor Contributing to Resilience After Disasters. AB - OBJECTIVE: Strategy-situation fit, or contextual coping, posits that the physical and psychological demands associated with stressors are determined in part by the characteristics of each stress situation and may therefore require the use of different coping strategies. In this review, we discuss strategy-situation fit in the context of both natural and manmade disasters as it pertains to positivity and, ultimately, resilience after disasters. METHOD: We reviewed the relevant literature on positivity and coping with disasters using a contextual approach. RESULTS: We identified several disaster-related characteristics (i.e., cause of disaster, temporal characteristics of disasters, and degree of resource loss) that might influence the efficacy of positive coping strategies. We then discussed strategies that could be useful for promoting resilience with regard to these different characteristics. CONCLUSION: This work represents an initial step in conceptualizing disaster resiliency within the framework of contextual positive coping. Recommendations for future avenues of research are discussed. PMID- 27410523 TI - Pain. PMID- 27410522 TI - SkfB Abstracts a Hydrogen Atom from Calpha on SkfA To Initiate Thioether Cross Link Formation. AB - Sulfur to alpha-carbon thioether-containing peptides (sactipeptides) are ribosomally synthesized post-translationally modified peptides with bacteriocidal activities. The thioether cross-link, which is required for biological activity, is installed by a member of the radical S-adenosyl-l-methionine (SAM) superfamily in the peptide substrate. Herein, we show that the radical SAM enzyme, SkfB, utilizes the 5'-deoxyadenosyl radical generated from the reductive cleavage of SAM to abstract a hydrogen atom from the alpha-carbon of the amino acid at position 12 in the substrate, SkfA, to initiate the installation of a thioether cross-link. The insights from this work can be applied to all radical SAM sactipeptide maturases. PMID- 27410524 TI - Neuropathy: A name for their pain. PMID- 27410525 TI - Genetics: An incomplete mosaic. PMID- 27410526 TI - Placebos: Honest fakery. PMID- 27410527 TI - Palliative care: The other opioid issue. PMID- 27410528 TI - Painful progress. PMID- 27410529 TI - The pain drain. PMID- 27410530 TI - Biomedicine: Move over, morphine. PMID- 27410531 TI - Perspective: Equality need not be painful. PMID- 27410532 TI - Imaging: Show me where it hurts. PMID- 27410534 TI - Optical bistability and multistability via quantum coherence in chiral molecules. AB - The optical bistability (OB) and multistability (OM) in chiral molecules are investigated by placing the sample into a unidirectional ring cavity. Because of broken mirror symmetry of the effective potential, the chiral molecules have a cyclic three-level Delta-configuration structure, in which one- and two-photon transitions can coexist. We find that the OB is achievable in this system on exact one-, two- and three-photon resonance conditions but absent in the three level Lambda-type system under the two-photon resonance. Moreover, the OM and the switching between OB and OM are also realized by choosing parameters properly. Interestingly, the left- and right-handed chiral molecules exhibit different bistable and multistable behaviors. It is shown that the threshold intensity of OB is strongly dependent on the percentage of the two enantiomers in the mixture. This provides an effective approach to probe molecular chirality and to determine enantiomer excess, which may find potential application in organic chemistry, pharmacology, biochemistry, etc.. PMID- 27410533 TI - Lack of Seasonal Differences in Basal Metabolic Rate in Humans: A Cross-Sectional Study. AB - Some studies indicate that basal metabolic rate is greater in winter than in the summer, suggesting a role for brown fat in human thermogenesis. We examined whether there are clinically meaningful differences in basal metabolic rate under thermoneutral conditions between winter and summer months in inhabitants of Rochester, Minnesota. We collated data from 220 research volunteers studied in the winter (December 1 - February 28) and 214 volunteers studied in the summer (June 1 - August 31), 1995-2012. Basal metabolic rate was measured by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. The effect of season on basal metabolic rate was tested using multivariate regression analysis with basal metabolic rate as the dependent variable and fat-free mass, fat mass, age, sex, and season as the independent variables. The groups were comparable with respect to age, body mass index, fat mass, and fat-free mass. There was no significant difference in basal metabolic rate between winter and summer groups (1 667+/-322 vs. 1 669+/-330 kcal/day). Both winter and summer basal metabolic rates were strongly predicted by fat-free mass (Pearson's r=0.75 and r=0.77, respectively, p <0.0001). Using multiple linear regression analysis, basal metabolic rate was significantly, independently predicted by fat-free mass, fat mass, age, and sex, but not season. We conclude that the lack of seasonal variation of thermoneutral basal metabolic rate between winter and summer suggests that modern, Western populations do not engage thermogenically detectable brown fat activity during periods of living in a cold climate. PMID- 27410535 TI - Vortex phase-induced changes of the statistical properties of a partially coherent radially polarized beam. AB - Partially coherent radially polarized (PCRP) beam was introduced and generated in recent years. In this paper, we investigate the statistical properties of a PCRP beam embedded with a vortex phase (i.e., PCRP vortex beam). We derive the analytical formula for the cross-spectral density matrix of a PCRP vortex beam propagating through a paraxial ABCD optical system and analyze the statistical properties of a PCRP vortex beam focused by a thin lens. It is found that the statistical properties of a PCRP vortex beam on propagation are much different from those of a PCRP beam. The vortex phase induces not only the rotation of the beam spot, but also the changes of the beam shape, the degree of polarization and the state of polarization. We also find that the vortex phase plays a role of resisting the coherence-induced degradation of the intensity distribution and the coherence-induced depolarization. Furthermore, we report experimental generation of a PCRP vortex beam for the first time. Our results will be useful for trapping and rotating particles, free-space optical communications and detection of phase object. PMID- 27410536 TI - Holographic imaging with a Shack-Hartmann wavefront sensor. AB - A high-resolution Shack-Hartmann wavefront sensor has been used for coherent holographic imaging, by computer reconstruction and propagation of the complex field in a lensless imaging setup. The resolution of the images obtained with the experimental data is in a good agreement with the diffraction theory. Although a proper calibration with a reference beam improves the image quality, the method has a potential for reference-less holographic imaging with spatially coherent monochromatic and narrowband polychromatic sources in microscopy and imaging through turbulence. PMID- 27410537 TI - Learning-based imaging through scattering media. AB - We present a machine-learning-based method for single-shot imaging through scattering media. The inverse scattering process was calculated based on a nonlinear regression algorithm by learning a number of training object-speckle pairs. In the experimental demonstration, multilayer phase objects between scattering plates were reconstructed from intensity measurements. Our approach enables model-free sensing, where it is not necessary to know the sensing processes/models. PMID- 27410538 TI - Dynamic phase measurement based on spatial carrier-frequency phase-shifting method. AB - Combining spatial carrier-frequency phase-shifting (SCPS) technique and Fourier transform method, from one-frame spatial carrier-frequency interferogram (SCFI), a novel phase retrieval method is proposed and applied to dynamic phase measurement. First, using the SCPS technique, four-frame phase-shifting sub interferograms can be constructed from one-frame SCFI. Second, using Fourier transform method, the accurate phase-shifts of four sub-interferograms can be extracted rapidly, so there is no requirement of calibration for the carrier frequency in advance compared to most existing SCPS methods. Third, the wrapped phase can be retrieved with the least-squares algorithm through using the above phase-shifts. Finally, the phase variations of a water droplet evaporation and a Jurkat cell apoptosis induced by a drug are presented with the proposed method. Both the simulation and experimental results demonstrate that in addition to maintaining high accuracy of the SCPS method, the proposed method reveals more rapid processing speed of phase retrieval, and this will greatly facilitate its application in dynamic phase measurement. PMID- 27410539 TI - Transfer-printing-based integration of single-mode waveguide-coupled III-V-on silicon broadband light emitters. AB - We present the first III-V opto-electronic components transfer printed on and coupled to a silicon photonic integrated circuit. Thin InP-based membranes are transferred to an SOI waveguide circuit, after which a single-spatial-mode broadband light source is fabricated. The process flow to create transfer print ready coupons is discussed. Aqueous FeCl3 at 5 degrees C was found to be the best release agent in combination with the photoresist anchoring structures that were used. A thin DVS-BCB layer provides a strong bond, accommodating the post-processing of the membranes. The resulting optically pumped LED has a 3 dB bandwidth of 130 nm, comparable to devices realized using a traditional die-to-wafer bonding method. PMID- 27410540 TI - SBS reduction in nanosecond fiber amplifiers by frequency chirping. AB - We demonstrate a technique for SBS reduction in a nanosecond Yb-fiber amplifier by imposing 1.19 GHz/ns frequency chirp on the seed pulses with a pulse-driven phase modulator. A nearly 9-fold increase in the SBS threshold was observed for 8.4 ns pulses. SBS threshold data and transient SBS gain for various degrees of chirp are reported and compared with theoretical calculations. We further demonstrate the recovery of the input narrowband spectrum by applying an opposite chirp with a second phase modulator after the amplification. PMID- 27410541 TI - High energy noise-like pulsing in a double-clad Er/Yb figure-of-eight fiber laser. AB - In this work, we study a 215-m-long figure-of-eight fiber laser including a double-clad erbium-ytterbium fiber and a nonlinear optical loop mirror based on nonlinear polarization evolution. For proper adjustments, self-starting passive mode-locking is obtained. Measurements show that the mode-locked pulses actually are noise-like pulses, by analyzing the autocorrelation, scope traces and the very broad and flat spectrum extending over a record bandwidth of more than 200 nm, beyond the 1750 nm upper wavelength limit of the optical spectrum analyzer. Noise-like pulsing was observed for moderate and high pump power preserving the same behavior, reaching pulse energies as high as 300 nJ, with pulse durations of a few tens of ns and a coherence length in the order of 1 ps. Stable fundamental mode locking as well as harmonic mode locking up to the 6th order were observed. The bandwidth was further extended to more than 450 nm when a 100-m piece of highly nonlinear fiber was inserted at the laser output. The enhanced performances obtained compared to other similar schemes could be related to the absence of a polarizer in the present setup, so that the state of polarization along the cavity is no longer restricted. PMID- 27410542 TI - Optical spin-sensitive Zitterbewegung in bianisotropic metamaterials. AB - We present a theoretical analysis on optical spin-sensitive Zitterbewegung (ZB) in metamaterials. By developing some formulas about the dispersions and eigenstates of optical modes we show that spin-sensitive ZB can be obtained in a bianisotropic metamaterial with a proper coupling between the electric and magnetic responses. A close analogue of the developed analytical results with these of Dirac equation is proposed. Numerical simulation proves the existence of ZB on the refracted optical beam along a direction determined by the optical spin of incidence. Furthermore, we show that when the incident optical field is linearly polarized, although ZB on field intensity does not exist, the optical spin possesses an interesting spatial split and trembling phenomena. Significance of this investigation is discussed. PMID- 27410543 TI - Transcoder for the spatial and temporal modes of a photon. AB - Encoding information in light with orbital angular momentum (OAM) enables networks to increase channel capacity significantly. However, light in only the fundamental Gaussian mode is suitable for fibre transmission, and not higher order Laguerre Gaussian modes, which carry OAM. Therefore, building a bridge to interface light with OAM and Gaussian mode time-binning is crucially important. Here, we report the realization of a photonic transcoder, by which light with an arbitrary OAM superposition is experimentally converted into a time-bin Gaussian pulse, and vice versa. Furthermore, we clearly demonstrate that coherence is well conserved and there is no cross-talk between orthogonal modes. This photonic device is simple and can be built with scalable architecture. Our experimental demonstration paves the way towards a mixed optical communication in free-space and optical fibre. PMID- 27410544 TI - Broadband optical switch based on liquid crystal dynamic scattering. AB - This work demonstrates a novel broadband optical switch, based on dynamic scattering effect in liquid crystals (LCs). Dynamic-scattering-mode technology was developed for display applications over four decades ago, but was displaced in favor of the twisted-nematic LCs. However, with the recent development of more stable LCs, dynamic scattering provides advantages over other technologies for optical switching. We demonstrate broadband polarization-insensitive attenuation of light directly passing thought the cell by 4 to 5 orders of magnitude at 633 nm. The attenuation is accomplished by light scattering to higher angles. Switching times of 150 MUs to 10% transmission have been demonstrated. No degradation of devices is found after hundreds of switching cycles. The light rejection mechanism is due to scattering, induced by disruption of LC director orientation with dopant ion motion with an applied electric field. Angular dependence of scattering is characterized as a function of bias voltage. PMID- 27410545 TI - Emission efficiency enhanced by reducing the concentration of residual carbon impurities in InGaN/GaN multiple quantum well light emitting diodes. AB - A series of samples with varying growth pressure are grown and their optical and structural properties are investigated. It is found that the residual carbon concentration decreases when the reactor pressure increases from 80 to 450 Torr during the InGaN/GaN multiple quantum well growth. It results in an enhanced peak intensity of electroluminescence because carbon impurities can induce deep energy levels and act as non-radiative recombination centers in InGaN layers. PMID- 27410546 TI - Mode coupling in metal-coated microsphere. AB - Mode coupling characteristics in metal-coated microsphere are comprehensively studied by analytical method with Mie theory. The dispersion relation, field distribution and Q factor of the eigenmodes are calculated according to the modal eigenequation. In metal-coated microcavity, symmetric SPP mode can couple with asymmetric SPP mode and TM eigenmodes strongly at the different characteristic radius of microsphere. In the coupling range, the generated supermode possesses both high Q factor and high surface enhancement factor, which is expected to have many interesting potential applications. Furthermore, the sensitivity and figure of merit of supermode in biochemical sensing applications has been studied. The results show that both high sensitivity and large figure of merit can be achieved simultaneously. PMID- 27410547 TI - High-spectral-resolution terahertz imaging with a quantum-cascade laser. AB - We report on a high-spectral-resolution terahertz imaging system operating with a multi-mode quantum-cascade laser (QCL), a fast scanning mirror, and a sensitive Ge:Ga detector. By tuning the frequency of the QCL, several spectra can be recorded in 1.5 s during the scan through a gas cell filled with methanol (CH3OH). These experiments yield information about the local absorption and the linewidth. Measurements with a faster frame rate of up to 3 Hz allow for the dynamic observation of CH3OH gas leaking from a terahertz-transparent tube into the evacuated cell. In addition to the relative absorption, the local pressure is mapped by exploiting the effect of pressure broadening. PMID- 27410548 TI - Strong optomechanical coupling in a slotted photonic crystal nanobeam cavity with an ultrahigh quality factor-to-mode volume ratio. AB - We describe the design, fabrication, and characterization of a one-dimensional silicon photonic crystal cavity in which a central slot is used to enhance the overlap between highly localized optical and mechanical modes. The optical mode has an extremely small mode volume of 0.017(lambdavac / n)3, and an optomechanical vacuum coupling rate of 310 kHz is measured for a mechanical mode at 2.69 GHz. With optical quality factors up to 1.2 * 105, fabricated devices are in the resolved-sideband regime. The electric field has its maximum at the slot wall and couples to the in-plane breathing motion of the slot. The optomechanical coupling is thus dominated by the moving-boundary effect, which we simulate to be six times greater than the photoelastic effect, in contrast to most structures, where the photoelastic effect is often the primary coupling mechanism. PMID- 27410549 TI - Advanced GF(32) nonbinary LDPC coded modulation with non-uniform 9-QAM outperforming star 8-QAM. AB - In this paper, we first describe a 9-symbol non-uniform signaling scheme based on Huffman code, in which different symbols are transmitted with different probabilities. By using the Huffman procedure, prefix code is designed to approach the optimal performance. Then, we introduce an algorithm to determine the optimal signal constellation sets for our proposed non-uniform scheme with the criterion of maximizing constellation figure of merit (CFM). The proposed nonuniform polarization multiplexed signaling 9-QAM scheme has the same spectral efficiency as the conventional 8-QAM. Additionally, we propose a specially designed GF(32) nonbinary quasi-cyclic LDPC code for the coded modulation system based on the 9-QAM non-uniform scheme. Further, we study the efficiency of our proposed non-uniform 9-QAM, combined with nonbinary LDPC coding, and demonstrate by Monte Carlo simulation that the proposed GF(23) nonbinary LDPC coded 9-QAM scheme outperforms nonbinary LDPC coded uniform 8-QAM by at least 0.8dB. PMID- 27410550 TI - Integrated metaphotonics: symmetries and confined excitation of LSP resonances in a single metallic nanoparticle. AB - Using numerical simulations, we demonstrate that the dipolar plasmonic resonance of a single metallic nanoparticle inserted in the core of a dielectric waveguide can be excited with higher order photonic modes of the waveguide only if their symmetry is compatible with the charge distribution of the plasmonic mode. For the case of a symmetric waveguide, we demonstrate that this condition is only achieved if the particle is shifted from the center of the core. The simple and comprehensive analysis presented in this contribution will serve as basis for applications in integrated nanophotonic/metamaterials devices, such as optical filters, modulators and mode converters. PMID- 27410551 TI - Ultra-precise holographic beam shaping for microscopic quantum control. AB - High-resolution addressing of individual ultracold atoms, trapped ions or solid state emitters allows for exquisite control in quantum optics experiments. This becomes possible through large aperture magnifying optics that project microscopic light patterns with diffraction limited performance. We use programmable amplitude holograms generated on a digital micromirror device to create arbitrary microscopic beam shapes with full phase and amplitude control. The system self-corrects for aberrations of up to several lambda and reduces them to lambda/50, leading to light patterns with a precision on the 10-4 level. We demonstrate aberration-compensated beam shaping in an optical lattice experiment and perform single-site addressing in a quantum gas microscope for 87Rb. PMID- 27410552 TI - Optimizing Laguerre expansion based deconvolution methods for analysing bi exponential fluorescence lifetime images. AB - Fast deconvolution is an essential step to calibrate instrument responses in big fluorescence lifetime imaging microscopy (FLIM) image analysis. This paper examined a computationally effective least squares deconvolution method based on Laguerre expansion (LSD-LE), recently developed for clinical diagnosis applications, and proposed new criteria for selecting Laguerre basis functions (LBFs) without considering the mutual orthonormalities between LBFs. Compared with the previously reported LSD-LE, the improved LSD-LE allows to use a higher laser repetition rate, reducing the acquisition time per measurement. Moreover, we extended it, for the first time, to analyze bi-exponential fluorescence decays for more general FLIM-FRET applications. The proposed method was tested on both synthesized bi-exponential and realistic FLIM data for studying the endocytosis of gold nanorods in Hek293 cells. Compared with the previously reported constrained LSD-LE, it shows promising results. PMID- 27410553 TI - Quantitative temperature measurement of multi-layered semiconductor devices using spectroscopic thermoreflectance microscopy. AB - Thermoreflectance microscopy is essential in understanding the unpredictable local heating generation that occurs during microelectronic device operation. However, temperature measurements of multi-layered semiconductor devices represent a challenge because the thermoreflectance coefficient is quite small and is dramatically changed by the optical interference inside transparent layers of the device. Therefore, we propose a spectroscopic thermoreflectance microscopy system using a systematic approach for improving the quantitative temperature measurement of multi-layered semiconductor devices. We demonstrate the quantitative measurement of the temperature profile for physical defects on thin film polycrystalline silicon resistors via thermoreflectance coefficient calibration and effective coefficient kappa estimation. PMID- 27410554 TI - Broadband opto-electro-mechanical effective refractive index tuning on a chip. AB - Photonic integrated circuits have enabled progressively active functionality in compact devices with the potential for large-scale integration. To date the lowest loss photonic circuits are achieved with silica or silicon nitride-based platforms. However, these materials generally lack reconfigurability. In this work we present a platform for achieving active functionality in any dielectric waveguide via large-scale opto-electro-mechanical tuning of the effective refractive index (Deltaneff~0.01-0.1) and phase (Deltaphi>2pi). A suspended microbridge weakly interacts with the evanescent field of a low-mode confinement waveguide to tune the effective refractive index and phase with minimal loss. Metal-coated bridges enable electrostatic actuation to displace the microbridge to dynamically tune nEFF. In a second implementation we place a non-metallized dielectric microbridge in a gradient electric field to achieve actuation and tuning. Both approaches are broadband, universally applicable to any waveguide, and pave the way for adding active functionality to many passive optical materials. PMID- 27410555 TI - Nano-optical single-photon response mapping of waveguide integrated molybdenum silicide (MoSi) superconducting nanowires. AB - We present low temperature nano-optical characterization of a silicon-on insulator (SOI) waveguide integrated SNSPD. The SNSPD is fabricated from an amorphous Mo83Si17 thin film chosen to give excellent substrate conformity. At 350 mK, the SNSPD exhibits a uniform photoresponse under perpendicular illumination, corresponding to a maximum system detection efficiency of approximately 5% at 1550 nm wavelength. Under these conditions 10 Hz dark count rate and 51 ps full width at half maximum (FWHM) timing jitter is observed. PMID- 27410556 TI - Mid-IR supercontinuum pumped by femtosecond pulses from thulium doped all-fiber amplifier. AB - We present a mid-infrared (mid-IR) supercontinuum (SC) light source pumped by femtosecond pulses from a thulium doped fiber amplifier (TDFA) at 2 MUm. An octave-spanning spectrum from 1.1 to 3.7 MUm with an average power of 253 mW has been obtained from a single mode ZBLAN fiber. Spectral flatness of 10 dB over a 1390 nm range has been obtained in the mid-IR region from 1940 - 3330 nm. It is resulted from the enhanced self phase modulation process in femtosecond regime. The all-fiber configuration makes such broadband coherent source a compact candidate for various applications. PMID- 27410558 TI - High power, diffraction limited picosecond oscillator based on Nd:GdVO4 bulk crystal with sigma polarized in-band pumping. AB - We report on a high power passively mode-locked picosecond oscillator based on Nd:GdVO4 crystal with sigma polarized in-band pumping. Thermal gradient and thermal aberration was greatly decreased with proposed configuration. Maximum output power of 37 W at 81 MHz repetition rate with 19.3 ps pulse duration was achieved directly from Nd:GdVO4 oscillator, corresponding to 51% optical efficiency. The oscillator maintained diffraction limited beam quality of M2 < 1.05 at different output coupling with pulse duration between 11.2 ps to 19.3 ps. PMID- 27410557 TI - High gain holmium-doped fibre amplifiers. AB - We investigate the operation of holmium-doped fibre amplifiers (HDFAs) in the 2.1 um spectral region. For the first time we demonstrate a diode-pumped HDFA. This amplifier provides a peak gain of 25 dB at 2040 nm with a 15 dB gain window spanning the wavelength range 2030 - 2100 nm with an external noise figure (NF) of 4-6 dB. We also compare the operation of HDFAs when pumped at 1950 nm and 2008 nm. The 1950 nm pumped HDFA provides 41 dB peak gain at 2060 nm with 15 dB of gain spanning the wavelength range 2050 - 2120 nm and an external NF of 7-10 dB. By pumping at the longer wavelength of 2008 nm the gain bandwidth of the amplifier is shifted to longer wavelengths and using this architecture a HDFA was demonstrated with a peak gain of 39 dB at 2090 nm and 15 dB of gain spanning the wavelength range 2050 - 2150 nm. The external NF over this wavelength range was 8 14 dB. PMID- 27410559 TI - Megahertz-level, high-power picosecond Nd:LuVO4 regenerative amplifier free of period doubling. AB - We report on a high repetition rate, high-power picosecond Nd:LuVO4 regenerative amplifier. Period doubling caused energy instability was eliminated at megahertz-level repetition rate with the modified seeding source. A multi-pass cell was used to improve the seed pulse energy to achieve complete suppression of the onset of bifurcation. At a maximum repetition rate of 1.43 MHz, the system produced 7.0-ps-long pulses with an average output power of 25.1 W, corresponding to a pulse energy of 17.6 MUJ. At 100 kHz, the pulse energy increased to 205 MUJ with an average power of 20.5 W. Moreover, the injected pulses with pulse duration of 5.1 ps broadened to 8.9 ps because of gain narrowing in the amplifier. PMID- 27410560 TI - Two-color high-harmonic generation in plasmas: efficiency dependence on the generating particle properties. AB - The high-order harmonic generation (HHG) in silver, gold, and zinc plasma plumes irradiated by orthogonally polarized two-color field is studied theoretically and experimentally. We find an increase of the HHG efficiency in comparison with the single-color case, which essentially depends on the plasma species and harmonic order. An increase of more than an order of magnitude is observed for silver plasma, whereas for gold and zinc it is lower; these results are reproduced in our calculations that include both propagation and microscopic response studies. We show that the widely used theoretical approach assuming the 1s ground state of the generating particle fails to reproduce the experimental results; the agreement is achieved in our theory using the actual quantum numbers of the outer electron of the generating particles. Moreover, our theoretical studies highlight the redistribution of the electronic density in the continuum wave packet as an important aspect of the HHG enhancement in the two-color orthogonally polarized fields with comparable intensities: in the single-color field the electronic trajectories with almost zero return energy are the most populated ones; in the two-color case the total field maximum can be shifted in time so that the trajectories with high return energies (in particular, the cut-off trajectory) become the most populated ones. PMID- 27410561 TI - Real-time demonstration of QoS guaranteed 25-Gb/s PON prototype with Ethernet-PON MAC/PHY and cost-effective APD receivers for 100-Gb/s access networks. AB - We demonstrate a real-time 25-Gb/s PON prototype with ethernet-PON MAC/PHY, O band transmitter, and cost-effective APD receivers. With applying parasitic inductance and capacitance reduction, the frequency response of 25-Gb/s APD ROSA with TO46-pacakge is improved to support high receiver sensitivity around -25 dBm at the BER of 10-3. The 30 dB power budget of 25 Gb/s downstream is achieved at the BER of 10-3. With long-term ethernet packet transmission, 25 Gigabit and 10 Gigabit ethernet traffics are successfully transmitted through the 20-km SMF over 14 hour's observation window. Furthermore, QoS and bandwidth re-assignment function of the 25-Gb/s PON prototype are successfully demonstrated with respect to residential, business and mobile backhaul services in ONUs. PMID- 27410562 TI - Superlens induced loss-insensitive optical force. AB - A slab with relative permittivity E = -1+idelta and permeability MU = -1+idelta has a critical distance away from the slab where a small particle will either be cloaked or imaged depending on whether it is located inside or outside that critical distance. We find that the optical force acting on a small cylinder under plane wave illumination reaches a maximum value at this critical distance. Contrary to the usual observation that superlens systems should be highly loss sensitive, this maximum optical force remains a constant when loss is changed within a certain range. For a fixed particle-slab distance, increasing loss can even amplify the optical force acting on the small cylinder, contrary to the usual belief that loss compromises the response of supenlens. PMID- 27410563 TI - Enhanced UV upconversion emission using plasmonic nanocavities. AB - Upconversion of near infrared (NIR) into ultraviolet (UV) radiation could lead to a number of applications in bio-imaging, diagnostics and drug delivery. However, for bare nanoparticles, the conversion efficiency is extremely low. In this work, we experimentally demonstrate strongly enhanced upconversion emission from an ensemble of beta-NaYF4:Gd3+/Yb3+/Tm3+ @NaLuF4 core-shell nanoparticles trapped in judiciously designed plasmonic nanocavities. In doing so, different metal platforms and nanostructures are systematically investigated. Our results indicate that using a cross-shape silver nanocavity, a record high enhancement of 170-fold can be obtained in the UV band centered at a wavelength of 345 nm. The observed upconversion efficiency improvement may be attributed to the increased absorption at NIR, the tailored photonic local density of states, and the light out-coupling characteristics of the cavity. PMID- 27410564 TI - Light-trapping for room temperature Bose-Einstein condensation in InGaAs quantum wells. AB - We demonstrate the possibility of room-temperature, thermal equilibrium Bose Einstein condensation (BEC) of exciton-polaritons in a multiple quantum well (QW) system composed of InGaAs quantum wells surrounded by InP barriers, allowing for the emission of light near telecommunication wavelengths. The QWs are embedded in a cavity consisting of double slanted pore (SP2) photonic crystals composed of InP. We consider exciton-polaritons that result from the strong coupling between the multiple quantum well excitons and photons in the lowest planar guided mode within the photonic band gap (PBG) of the photonic crystal cavity. The collective coupling of three QWs results in a vacuum Rabi splitting of 3% of the bare exciton recombination energy. Due to the full three-dimensional PBG exhibited by the SP2 photonic crystal (16% gap to mid-gap frequency ratio), the radiative decay of polaritons is eliminated in all directions. Due to the short exciton phonon scattering time in InGaAs quantum wells of 0.5 ps and the exciton non radiative decay time of 200 ps at room temperature, polaritons can achieve thermal equilibrium with the host lattice to form an equilibrium BEC. Using a SP2 photonic crystal with a lattice constant of a = 516 nm, a unit cell height of 2a=730nm and a pore radius of 0.305a = 157 nm, light in the lowest planar guided mode is strongly localized in the central slab layer. The central slab layer consists of 3 nm InGaAs quantum wells with 7 nm InP barriers, in which excitons have a recombination energy of 0.944 eV, a binding energy of 7 meV and a Bohr radius of aB = 10 nm. We take the exciton recombination energy to be detuned 35 meV above the lowest guided photonic mode so that an exciton-polariton has a photonic fraction of approximately 97% per QW. This increases the energy range of small-effective-mass photonlike states and increases the critical temperature for the onset of a Bose-Einstein condensate. With three quantum wells in the central slab layer, the strong light confinement results in light-matter coupling strength of hOmega = 13.7 meV. Assuming an exciton density per QW of (15aB) 2, well below the saturation density, in a 2-D box-trap with a side length of 10 to 500 um, we predict thermal equilibrium Bose-Einstein condensation well above room temperature. PMID- 27410566 TI - Simultaneous measurement of temperature and refractive index using focused ion beam milled Fabry-Perot cavities in optical fiber micro-tips. AB - Optical fiber micro-tips are promising devices for sensing applications in small volume and difficult to access locations, such as biological and biomedical settings. The tapered fiber tips are prepared by dynamic chemical etching, reducing the size from 125 MUm to just a few MUm. Focused ion beam milling is then used to create cavity structures on the tapered fiber tips. Two different Fabry-Perot micro-cavities have been prepared and characterized: a solid silica cavity created by milling two thin slots and a gap cavity. A third multi-cavity structure is fabricated by combining the concepts of solid silica cavity and gap cavity. This micro-tip structure is analyzed using a fast Fourier transform method to demultiplex the signals of each cavity. Simultaneous measurement of temperature and external refractive index is then demonstrated, presenting sensitivities of - 15.8 pm/K and -1316 nm/RIU, respectively. PMID- 27410565 TI - Optical closure in marine waters from in situ inherent optical property measurements. AB - Optical closure using radiative transfer simulations can be used to determine the consistency of in situ measurements of inherent optical properties (IOPs) and radiometry. Three scattering corrections are applied to in situ absorption and attenuation profile data for a range of coastal and oceanic waters, but are found to have only very limited impact on subsequent closure attempts for these stations. Best-fit regressions on log-transformed measured and modelled downwards irradiance, Ed, and upwards radiance, Lu, profiles have median slopes between 0.92 - 1.24, revealing a tendency to underestimate Ed and Lu with depth. This is only partly explained by non-inclusion of fluorescence emission from CDOM and chlorophyll in the simulations. There are several stations where multiple volume scattering function related data processing steps perform poorly which suggests the potential existence of unresolved features in the modelling of the angular distribution of scattered photons. General optical closure therefore remains problematic, even though there are many cases in the data set where the match between measured and modelled radiometric data is within 25% RMS%E. These results are significant for applications that rely on optical closure e.g. assimilating ocean colour data into coupled physical-ecosystem models. PMID- 27410567 TI - Accurate method for computing correlated color temperature. AB - For the correlated color temperature (CCT) of a light source to be estimated, a nonlinear optimization problem must be solved. In all previous methods available to compute CCT, the objective function has only been approximated, and their predictions have achieved limited accuracy. For example, different unacceptable CCT values have been predicted for light sources located on the same isotemperature line. In this paper, we propose to compute CCT using the Newton method, which requires the first and second derivatives of the objective function. Following the current recommendation by the International Commission on Illumination (CIE) for the computation of tristimulus values (summations at 1 nm steps from 360 nm to 830 nm), the objective function and its first and second derivatives are explicitly given and used in our computations. Comprehensive tests demonstrate that the proposed method, together with an initial estimation of CCT using Robertson's method [J. Opt. Soc. Am. 58, 1528-1535 (1968)], gives highly accurate predictions below 0.0012 K for light sources with CCTs ranging from 500 K to 106 K. PMID- 27410568 TI - BOTDA sensors enhanced using high-efficiency second-order distributed Brillouin amplification. AB - A novel approach for long-distance sensing through Brillouin optical time-domain analysis (BOTDA) assisted by second-order distributed Brillouin amplification (DBA) was proposed and experimentally demonstrated. To the best of our knowledge, this is the first BOTDA study that used second-order DBA. Compared with BOTDA assisted by first-order DBA, the proposed approach enhanced the signal-to-noise ratio of the Brillouin trace by ~3 dB for a range featuring minimum sensing intensity. Long-distance sensing with ~5 m spatial resolution and +/- 1.6 degrees C measurement uncertainty over ~99 km fiber was successfully realized by employing high-efficiency pumping using ~6 dBm second-order and ~1.5 dBm first order pumps. PMID- 27410569 TI - In-fiber Mach-Zehnder interferometer for gas refractive index measurements based on a hollow-core photonic crystal fiber. AB - We describe an in-fiber interferometer based on a gas-filled hollow-core photonic crystal fiber. Expressions for the sensitivity, figure of merit and refractive index resolution are derived, and values are experimentally measured and theoretically validated using mode field calculations. The refractive indices of nine monoatomic and molecular gases are measured with a resolution of deltans < 10-6. PMID- 27410570 TI - Continuous-feed optical sorting of aerosol particles. AB - We consider the problem of sorting, by size, spherical particles of order 100 nm radius. The scheme we analyze consists of a heterogeneous stream of spherical particles flowing at an oblique angle across an optical Gaussian mode standing wave. Sorting is achieved by the combined spatial and size dependencies of the optical force. Particles of all sizes enter the flow at a point, but exit at different locations depending on size. Exiting particles may be detected optically or separated for further processing. The scheme has the advantages of accommodating a high throughput, producing a continuous stream of continuously dispersed particles, and exhibiting excellent size resolution. We performed detailed Monte Carlo simulations of particle trajectories through the optical field under the influence of convective air flow. We also developed a method for deriving effective velocities and diffusion constants from the Fokker-Planck equation that can generate equivalent results much more quickly. With an optical wavelength of 1064 nm, polystyrene particles with radii in the neighborhood of 275 nm, for which the optical force vanishes, may be sorted with a resolution below 1 nm. PMID- 27410571 TI - Influence of a three-dimensional photonic crystal on the plasmonic properties of gold nanorods. AB - The influence of a three-dimensional (3D) photonic crystal (PC) on the plasmonic properties of gold nanorods (GNRs), which are placed on the surface of the PC, was investigated both numerically and experimentally. The 3D PC formed by closely packed polystyrene spheres was fabricated by using a pressure controlled isothermal heating vertical deposition technique. For a GNR whose longitudinal surface plasmon resonance (LSPR) is located at the bandgap edges of the PC, a dramatic narrowing of the absorption spectrum as well as an enhancement in electric field and thus the absorption was observed. It was suggested that the small group velocities at the bandgap edges of the PC are responsible for the slow decay of the plasmonic mode in the GNR. To confirm the enhancement in the absorption of the GNRs induced by the nearby PC, we examined the two-photon induced luminescence (TPL) of an assembly of GNRs dispersed on the surface of the PC. Under the excitation of femtosecond laser pulses which was resonant with the LSPR of GNRs, it was found that the excitation intensity necessary for melting GNRs placed on the surface of the PC was nearly one order of magnitude smaller than that for GNRs placed on the surface of a glass slide, in good agreement with the results predicted by the numerical simulations. Our findings indicate the possibility of using PCs to modify the plasmonic and optical properties of GNRs which are quite useful for the practical applications of GNRs such as nanoscale sensors and optical data storage. PMID- 27410572 TI - See-through multi-projection three-dimensional display using transparent anisotropic diffuser. AB - We propose a see-through multi-projection three-dimensional (3D) display using a transparent anisotropic diffuser. By immersing a metal-coated anisotropic diffuser into index matching oil which has the same refractive index of anisotropic diffuser, a transparent anisotropic diffuser is implemented. The reflectance of the transparent anisotropic diffuser is analyzed with the transfer matrix. Two multi-projection methods are proposed based on reflection type integral imaging and multi-view method. Especially, the reflection type multi view-based system is realized with a curved anisotropic diffuser. High resolution see-through 3D display can be realized with the proposed methods. They can be used in various applications with the two multi-projection methods. In order to show the augmented reality features, real objects and virtual 3D images are presented at the same time in the experimental setup. PMID- 27410574 TI - Interferometric method for phase calibration in liquid crystal spatial light modulators using a self-generated diffraction-grating. AB - An auto-referenced interferometric method for calibrating phase modulation of parallel-aligned liquid crystal (PAL) spatial light modulators (SLM) is described. The method is experimentally straightforward, robust, and requires solely of a collimated beam, with no need of additional optics. This method uses the SLM itself to create a tilted plane wave and a reference wave which mutually interfere. These waves are codified by means of a binary diffraction grating and a uniformly distributed gray level area (piston) into the SLM surface. Phase shift for each gray level addressed to the piston section can then be evaluated. Phase modulation on the SLM can also be retrieved with the proposed method over spatially resolved portions of the surface. Phase information obtained with this novel method is compared to other well established calibration procedures, requiring extra elements and more elaborated optical set-ups. The results show a good agreement with previous methods. The advantages of the new method include high mechanical stability, faster performance, and a significantly easier practical implementation. PMID- 27410573 TI - All-fiber Tm-doped soliton laser oscillator with 6 nJ pulse energy based on evanescent field interaction with monoloayer graphene saturable absorber. AB - We demonstrate an all-fiber Tm-doped soliton laser with high power by using a monolayer graphene saturable absorber (SA). Large area, uniform monolayer graphene was transferred to the surface of the side-polished fiber (SPF) to realize an in-line graphene SA that operates around 2 MUm wavelength. To increase the nonlinear interaction with graphene, we applied an over-cladding onto the SPF, where enhanced optical absorption at monolayer graphene was observed. All fiber Tm-doped mode-locked laser was built including our in-line graphene SA, which stably delivered the soliton pulses with 773 fs pulse duration. The measured 3-dB spectral bandwidth was 5.14 nm at the wavelength of 1910 nm. We obtained the maximum average output power of 115 mW at a repetition rate of 19.31 MHz. Corresponding pulse energy was estimated to be 6 nJ, which is the highest value among all-fiber Tm-doped soliton oscillators using carbon-material-based SAs. PMID- 27410575 TI - Non-diffractive computational ghost imaging. AB - Computational ghost imaging (CGI) enables an image to be recorded using a single pixel detector. The image can be reconstructed from correlations between the scene and a series of known projected intensity patterns. In this work we investigate the performance of CGI using pseudo non-diffracting (ND) speckle patterns. We demonstrate an extended depth-of-field that is ~ 2-3 times greater than that achievable with conventional speckle, when only computing each intensity pattern to a single depth. In addition, the average speckle grain size of ND speckle is reduced by a factor of ~ 1.5 relative to conventional speckle, which enhances the lateral Rayleigh-limit resolving power of our reconstructed images. However, the point-spread function (PSF) of our imaging system takes the form of a Bessel beam, which manifests itself as long-range correlations between speckle grains in the projected patterns. We discuss the trade-off between enhancement of the depth-of-field and the lateral resolution when using ND speckle, at the expense of a reduction in image contrast. Our work demonstrates that the tailoring of lateral and axial correlations in projected intensity patterns permits PSF engineering in CGI. PMID- 27410576 TI - Fringe periods of color moires in contact-type 3-D displays. AB - A mathematical formula of calculating the fringe periods of the color moires appearing at the contact-type 3-D displays is derived. It is typical that the color moires are chirped and the period of the line pattern in viewing zone forming optics is more than two times of that of the pixel pattern in the display panel. These make impossible to calculate the fringe periods of the color moires with the conventional beat frequency formula. The derived formula work very well for any combination of two line patterns having either a same line period or different line periods. This is experimentally proved. Furthermore, it is also shown that the fringe period can be expressed in terms of the viewing distance and focal length of the viewing zone forming optics. PMID- 27410577 TI - Pre-calibration-free 3D shape measurement method based on fringe projection. AB - This paper presents a pre-calibration-free 3D shape measurement method based on fringe projection. Unlike ordinary methods, it performs calibration and 3D shape measurement concurrently. The captured phase-coded fringe images are utilized to obtain homogenous control points from two camera viewpoints, and the rough 3D structure of these points can be retrieved. Further, a constrained non-linear least-squares optimization model is established to determine the in situ geometry of the optical components, and then, the 3D scene is reconstructed. This method provides an accurate 3D shape measurement capability even during disturbance of the optical geometry. Moreover, not requiring a preliminary calibration process makes the system ultra-flexible. The performance of this method was verified by experiments. PMID- 27410578 TI - 128-Gb/s 100-km transmission with direct detection using silicon photonic Stokes vector receiver and I/Q modulator. AB - Recently, there is increasing interest in utilizing Stokes vector receiver, which is a direct-detection technique with the capability to digitally track the polarization changes in fibers and decode information in multiple dimensions. Here, we report a monolithically integrated silicon photonic Stokes vector receiver, which consists of one polarization beam splitter, two polarization rotators, one 90-degree optical hybrid, and six germanium photodetectors. Paired with a silicon in-phase/quadrature modulator incorporating a power-tunable carrier in the orthogonal polarization, transmission at 128-Gb/s over 100-km fiber is achieved with direct detection. PMID- 27410579 TI - Experimental demonstration of a real-time high-throughput digital DC blocker for compensating ADC imperfections in optical fast-OFDM receivers. AB - Performance degradation induced by the DC components at the output of real-time analogue-to-digital converter (ADC) is experimentally investigated for optical fast-OFDM receiver. To compensate this degradation, register transfer level (RTL) circuits for real-time digital DC blocker with 20GS/s throughput are proposed and implemented in field programmable gate array (FPGA). The performance of the proposed real-time digital DC blocker is experimentally investigated in a 15Gb/s optical fast-OFDM system with intensity modulation and direct detection over 40 km standard single-mode fibre. The results show that the fixed-point DC blocker has negligible performance penalty compared to the offline floating point one, and can overcome the error floor of the fast OFDM receiver caused by the DC components from the real-time ADC output. PMID- 27410580 TI - Polarization-based control of spin-orbit vector modes of light in biphoton interference. AB - We report the experimental generation of a class of spin-orbit vector modes of light via an asymmetric Mach-Zehnder interferometer, obtained from an input beam prepared in a product state of its spin and orbital degrees of freedom. These modes contain a spatially varying polarization structure which may be controllably propagated about the beam axis by varying the retardance between the vertical and horizontal polarization components of the light. Additionally, their transverse spatial intensity distributions may be continuously manipulated by tuning the input polarization parameters. In the case of an analogous biphoton input, we predict that this device will exhibit biphoton (Hong-Ou-Mandel) interference in conjunction with the aforementioned tunable mode transformations. PMID- 27410581 TI - Optical filtering enabled by cascaded parametric amplification. AB - A cascaded parametric amplifier consists of a first parametric amplifier, which amplifies an input signal and generates an idler, which is a copy of the signal, a signal processor, which controls the phases of the signal and idler, and a second parametric amplifier, which combines the signal and idler in a phase sensitive manner. In this paper, cascaded parametric amplification is modeled and the conditions required to maximize the constructive-destructive extinction ratio are determined. The results show that a cascaded parametric amplifier can be operated as a filter: A desired signal-idler pair is amplified, whereas undesired signal-idler pairs are deamplified. For the desired signal and idler, the noise figures of the filtering process (input signal-to-noise ratio divided by the output ratios) are only slightly higher than those of the copying process: Signal processing functionality can be achieved with only a minor degradation in signal quality. PMID- 27410582 TI - One long and two short pumping pulses control for plasma x-ray amplifier optimization. AB - Development of efficient soft x-ray laser plasma amplifiers adapted to seeded operation, requires a better control over amplifier transverse spatial extent, brilliance control and gain lifetime. Here it is shown that pumping the plasma amplifier with one long and two short pump pulses (1L2S) provides advantages in terms of control for the specified parameters in the case of Ni-like Ag x-ray laser. Also, significant tunability of the gain lifetime in the 1L2S pumping scheme for Ne-like Ti x-ray laser is observed. Direct harmonics seeding and chirped harmonics seeding amplification approaches may benefit from the control of the gain lifetime, in terms of better use of the pump energy and as a way to reduce the amplified spontaneous emission in x-ray lasers. PMID- 27410583 TI - Ray mapping approach for the efficient design of continuous freeform surfaces. AB - The efficient design of continuous freeform surfaces, which maps a given light source to an arbitrary target illumination pattern, remains a challenging problem and is considered here for collimated input beams. A common approach are ray mapping methods, where first a ray mapping between the source and the irradiance distribution on the target plane is calculated and in a subsequent step the surface is constructed. The challenging aspect of this approach is to find an integrable mapping ensuring a continuous surface. Based on the law of reflection/refraction and an integrability condition, we derive a general condition for the surface and ray mapping for a collimated input beam. It is shown that in a small-angle approximation a proper mapping can be calculated via optimal mass transport - a mathematical framework for the calculation of a mapping between two positive density functions. We show that the surface can be constructed by solving a linear advection Eq. with appropriate boundary conditions. The results imply that the optimal mass transport mapping is approximately integrable over a wide range of distances between the freeform and the target plane and offer an efficient way to construct the surface by solving standard integrals. The efficiency is demonstrated by applying it to two challenging design examples, which shows the ability of the presented approach to handle target illumination patterns with steep irradiance gradients and numerous gray levels. PMID- 27410584 TI - Signal modeling in low coherence interference microscopy on example of rectangular grating. AB - Besides the illumination wavelength also the numerical aperture (NA) of a microscope objective affects the fringe spacing in interference microscopy. Therefore, at high NA values an effective wavelength should be obtained by calibration. At step height structures both, the effective wavelength and the batwing effect strongly depend on the height-to-wavelength-ratio (HWR). Therefore, changes of the effective wavelength considering temporal and spatial coherence enable us to estimate the batwing effect in measurement results. For high NA systems and broadband illumination two different theoretical approaches for signal modeling are introduced to study the influence of the center wavelength, the temporal, and the spatial coherence of the illuminating light on measurement results of a rectangular grating. In both models diffraction is considered. While the first simulation model (Kirchhoff) is mostly analytical the second one (Richards-Wolf) is primarily numerical. Simulation results of both models show a good agreement with experimental measurement results. PMID- 27410585 TI - Experimental demonstration of change of dynamical properties of a passively mode locked semiconductor laser subject to dual optical feedback by dual full delay range tuning. AB - In this contribution we experimentally demonstrate the change and improvement of dynamical properties of a passively mode-locked semiconductor laser subject to optical feedback from two external cavities by coupling the feedback pulses back into the gain segment. Hereby, we tune the full delay-phase of the pulse-to-pulse period of both external cavities separately and demonstrate the change of the repetition rate, timing jitter, multi-pulse formation and side-band suppression for the first time for such a dual feedback configuration. In addition, we thereby confirm modeling predictions by achieving both a good qualitative and quantitative agreement of experimental and simulated results. Our findings suggest a path towards the realization of side-band free all-optical photonic oscillators based on mode-locked lasers. PMID- 27410586 TI - Unidirectional reflectionless phenomenon in periodic ternary layered material. AB - Unidirectional reflectionless phenomenon is reported in periodic ternary layered material (PTLM). The unit of the material is composed of two real dielectric layers and a complex medium (loss or gain) layer. The model is analyzed by coupled mode theory. Because of the asymmetric coupling between the forward and backward propagating modes, the left- and right-side reflectivities of this PTLM are generally unequal. The necessary and sufficient (NS) condition for unidirectional reflectionless phenomenon is presented in a concise formulation. And the underlying physical mechanism of the unidirectional reflectionless phenomenon in this material is revealed by numerical simulations. Both unidirectional reflectionless and symmetric reflection phenomena can be realized by judicious choice of the structural and optical parameters. PMID- 27410587 TI - Quantitative appraisal for noise reduction in digital holographic phase imaging. AB - This paper discusses on a quantitative comparison of the performances of different advanced algorithms for phase data de-noising. In order to quantify the performances, several criteria are proposed: the gain in the signal-to-noise ratio, the Q index, the standard deviation of the phase error, and the signal to distortion ratio. The proposed methodology to investigate de-noising algorithms is based on the use of a realistic simulation of noise-corrupted phase data. A database including 25 fringe patterns divided into 5 patterns and 5 different signal-to-noise ratios was generated to evaluate the selected de-noising algorithms. A total of 34 algorithms divided into different families were evaluated. Quantitative appraisal leads to ranking within the considered criteria. A fairly good correlation between the signal-to-noise ratio gain and the quality index has been observed. There exists an anti-correlation between the phase error and the quality index which indicates that the phase errors are mainly structural distortions in the fringe pattern. Experimental results are thoroughly discussed in the paper. PMID- 27410588 TI - Active plasmonic band-stop filters based on graphene metamaterial at THz wavelengths. AB - Active plasmonic band-stop filters based on single- and double-layer doped graphene metamaterials at the THz wavelengths are proposed and investigated numerically by using the finite-difference time-domain (FDTD) method. The metamaterial unit cell structure is composed of two parallel graphene nanoscale ribbons. Simulated results exhibit that significant resonance wavelength shifts can be achieved with a slight variation of the doping concentration of the graphene ribbons. Besides, the asymmetry double-layer graphene metamaterial device has two apparent filter dips while the symmetry single-, double-layer and asymmetry single-layer graphene metamaterial devices just only one. The metamaterials with symmetry single-layer and asymmetry double-layer graphene can be used as a high-sensitivity refractive sensor with the sensitivity up to 5100 nm/RIU and a two-circuit switch, respectively. These prospects pave the way towards ultrafast active graphene-based plasmonic devices for THz applications. PMID- 27410589 TI - Role of quantum trajectory in high-order harmonic generation in the Keldysh multiphoton regime. AB - We present a systematic study of spectral and temporal structure of high-order harmonic generation (HHG) by solving accurately the time-dependent Schrodinger equation for a hydrogen atom in the multiphoton regime where the Keldysh parameter is greater unity. Combining with a time-frequency transform and an extended semiclassical analysis, we explore the role of quantum trajectory in HHG. We find that the time-frequency spectra of the HHG plateau near cutoff exhibit a decrease in intensity associated with the short- and long-trajectories when the ionization process is pushed from the multiphoton regime into the tunneling regime. This implies that the harmonic emission spectra in the region of the HHG plateau near and before the cutoff are suppressed. To see the generality of this prediction, we also present a time-dependent density functional theoretical study of the effect of correlated multi-electron responses on the spectral and temporal structure of the HHG plateau of the Ar atom. PMID- 27410590 TI - Jones calculus modeling and analysis of the thermal distortion in a Ti:sapphire laser amplifier. AB - The mathematical modeling of an anisotropic Ti:sapphire crystal with a significant thermal load is performed. The model is expressed by the differential Jones matrix. A thermally induced distortion in the chirped-pulse amplification process is shown by the solution of the differential Jones matrix. Using this model, the thermally distorted spatio-temporal laser beam shape is calculated for a high-power and high-repetition-rate Ti:sapphire amplifier. PMID- 27410591 TI - Influence of the pump-to-laser beam overlap on the performance of optically pumped cesium vapor laser. AB - Experimental and theoretical study of the influence of the pump-to-laser beam overlap, a crucial parameter for optimization of optically pumped alkali atom lasers, is reported for Ti:Sapphire pumped Cs laser. Maximum laser power > 370 mW with an optical-to-optical efficiency of 43% and slope efficiency ~55% was obtained. The dependence of the lasing power on the pump power was found for different pump beam radii at constant laser beam radius. Non monotonic dependence of the laser power (optimized over the temperature of the Cs cell) on the pump beam radius was observed with a maximum achieved at the ratio ~0.7 between the pump and laser beam radii. The optimal temperature decreased with increasing pump beam radius. A simple optical model of the laser, where Gaussian spatial shapes of the pump and laser intensities in any cross section of the beams were assumed, was compared to the experiments. Good agreement was obtained between the measured and calculated dependence of the laser power on the pump power at different pump beam radii and also of the laser power, threshold pump power and optimal temperature on the pump beam radius. The model does not use empirical parameters such as mode overlap efficiency and can be applied to different Ti:Sapphire and diode pumped alkali lasers with arbitrary spatial distributions of the pump and laser beam widths. PMID- 27410592 TI - Portable IR dye laser optofluidic microresonator as a temperature and chemical sensor. AB - A compact and portable optofluidic microresonator has been fabricated and characterized. It is based on a Fabry-Perot microcavity consisting essentially of two tailored dichroic Bragg mirrors prepared by reactive magnetron sputtering deposition. The microresonator has been filled with an ethanol solution of Nile Blue dye. Infrared laser emission has been measured with a pump threshold as low as 0.12 MW/cm2 and an external energy conversion efficiency of 41%. The application of the device as a temperature and a chemical sensor is demonstrated. Small temperature variations as well as small amount of water concentrations in the liquid laser medium are detected as a shift of the resonant laser modes. PMID- 27410593 TI - Holographic display system for dynamic synthesis of 3D light fields with increased space bandwidth product. AB - We present a new method for the generation of a dynamic wave field with high space bandwidth product (SBP). The dynamic wave field is generated from several wave fields diffracted by a display which comprises multiple spatial light modulators (SLMs) each having a comparably low SBP. In contrast to similar approaches in stereoscopy, we describe how the independently generated wave fields can be coherently superposed. A major benefit of the scheme is that the display system may be extended to provide an even larger display. A compact experimental configuration which is composed of four phase-only SLMs to realize the coherent combination of independent wave fields is presented. Effects of important technical parameters of the display system on the wave field generated across the observation plane are investigated. These effects include, e.g., the tilt of the individual SLM and the gap between the active areas of multiple SLMs. As an example of application, holographic reconstruction of a 3D object with parallax effects is demonstrated. PMID- 27410594 TI - Propagation dynamics of super-Gaussian beams in fractional Schrodinger equation: from linear to nonlinear regimes. AB - We have investigated the propagation dynamics of super-Gaussian optical beams in fractional Schrodinger equation. We have identified the difference between the propagation dynamics of super-Gaussian beams and that of Gaussian beams. We show that, the linear propagation dynamics of the super-Gaussian beams with order m > 1 undergo an initial compression phase before they split into two sub-beams. The sub-beams with saddle shape separate each other and their interval increases linearly with propagation distance. In the nonlinear regime, the super-Gaussian beams evolve to become a single soliton, breathing soliton or soliton pair depending on the order of super-Gaussian beams, nonlinearity, as well as the Levy index. In two dimensions, the linear evolution of super-Gaussian beams is similar to that for one dimension case, but the initial compression of the input super Gaussian beams and the diffraction of the splitting beams are much stronger than that for one dimension case. While the nonlinear propagation of the super Gaussian beams becomes much more unstable compared with that for the case of one dimension. Our results show the nonlinear effects can be tuned by varying the Levy index in the fractional Schrodinger equation for a fixed input power. PMID- 27410595 TI - Dynamic spectro-polarimeter based on a modified Michelson interferometric scheme. AB - A simple dynamic spectro-polarimeter based on a modified Michelson interferometric scheme is described. The proposed system can extract a spectral Stokes vector of a transmissive anisotropic object. Detail theoretical background is derived and experiments are conducted to verify the feasibility of the proposed novel snapshot spectro-polarimeter. The proposed dynamic spectro polarimeter enables us to extract highly accurate spectral Stokes vector of any transmissive anisotropic object with a frame rate of more than 20Hz. PMID- 27410596 TI - Effect of spatial coherence on laser beam self-focusing from orbit to the ground in the atmosphere. AB - The effect of spatial coherence on laser beam self-focusing in the atmosphere to assist delivering powerful laser beams from orbit to the ground is studied. It is found that a fully coherent beam is more strongly compressed on the ground than a partially (spatial) coherent beam (PCB), even so, for a PCB the compressed spot size on the ground may be reduced below the diffraction limit due to self focusing effect, and a PCB has higher threshold critical power than a fully coherent beam. Furthermore, an effective design rule for maximal compression without beam splitting of the transported PCB from orbit to the ground is presented. PMID- 27410597 TI - Experimental demonstration of a multi-target detection technique using an X-band optically steered phased array radar. AB - An X-band optically-steered phased array radar is developed to demonstrate high resolution multi-target detection. The beam forming is implemented based on wavelength-swept true time delay (TTD) technique. The beam forming system has a wide direction tuning range of +/- 54 degree, low magnitude ripple of +/- 0.5 dB and small delay error of 0.13 ps/nm. To further verify performance of the proposed optically-steered phased array radar, three experiments are then carried out to implement the single and multiple target detection. A linearly chirped X band microwave signal is used as radar signal which is finally compressed at the receiver to improve the detection accuracy. The ranging resolution for multi target detection is up to 2 cm within the measuring distance over 4 m and the azimuth angle error is less than 4 degree. PMID- 27410598 TI - Fano resonant all-dielectric core/shell nanoparticles with ultrahigh scattering directionality in the visible region. AB - We demonstrate Si-based single core/shell (Si/SiO2) nanoparticles which exhibit the Fano resonance associated with ultrahigh scattering directionality. The SiO2 shell plays a crucial role in achieving zero backscattering at the Fano resonance wavelength along with strongly-enhanced forward scattering. As a result, the front-to-back scattering-intensity ratio is five orders of magnitude greater than that of a Si nanoparticle. Furthermore, the Fano resonance wavelength is controlled over the entire visible region by changing the core diameter. The Fano spectra also show distinctive intensity modulations depending on the index of refraction of the surrounding medium. These unique features make Si/SiO2 nanoparticles promising for the design of low-loss nano-antennas, metamaterials, and other nanophotonic devices. PMID- 27410600 TI - Evanescent field trapping of nanoparticles using nanostructured ultrathin optical fibers. AB - While conventional optical trapping techniques can trap objects with submicron dimensions, the underlying limits imposed by the diffraction of light generally restrict their use to larger or higher refractive index particles. As the index and diameter decrease, the trapping difficulty rapidly increases; hence, the power requirements for stable trapping become so large as to quickly denature the trapped objects in such diffraction-limited systems. Here, we present an evanescent field-based device capable of confining low index nanoscale particles using modest optical powers as low as 1.2 mW, with additional applications in the field of cold atom trapping. Our experiment uses a nanostructured optical micro nanofiber to trap 200 nm, low index contrast, fluorescent particles within the structured region, thereby overcoming diffraction limitations. We analyze the trapping potential of this device both experimentally and theoretically, and show how strong optical traps are achieved with low input powers. PMID- 27410599 TI - High power all-fiber amplifier with different seed power injection. AB - We report a high power all-fiber amplifier with suitable seed power injected by an all-fiber laser. Different seed powers were injected into the all-fiber amplifier during our amplification experiments, and we found the stimulated Raman scattering (SRS) threshold was inversely proportional to the injected seed power. More than 3 kW signal light with good beam quality (M2 = 1.28) has been obtained with a suitable seed power injected, and the slope efficiency of the all-fiber amplifier was about 84.4%. PMID- 27410601 TI - Continuously tunable femtosecond delay-line based on liquid crystal cells. AB - We introduce a new device for group and phase delay steering of femtosecond pulse trains that makes use of cascaded, electrically driven, nematic liquid-crystal cells. Based on this approach we demonstrate a continuously tunable optical delay line. The simple collinear implementation with no moving parts enables to shape the achievable temporal range with sub-femtosecond accuracy. By appropriately choosing the bias voltages applied to the cascaded cells, the imparted group delay can be made either positive or negative and precisely adjusted. Moreover, independent control of the group delay and the phase of femtosecond pulses is demonstrated. PMID- 27410602 TI - Reduction of mode partition noise of FP-LD by using Mach-Zehnder interferometer for RSOA-based DWDM applications. AB - We investigate reduction of mode partition noise of a spectrally sliced Fabry Perot laser diode (FP-LD) for application to seeded DWDM systems. The proposed scheme for the noise reduction incorporates a fiber-based Mach-Zehnder interferometer (MZI) and a reflective semiconductor optical amplifier (RSOA). The MZI enables to reduce a relative intensity noise (RIN) more than 3 dB with better noise distributions. Experimental results of 10-Gb/s signal transmission exhibit a considerable bit-error-rate (BER) reduction by three orders of magnitude at the given received power. After the noise reduction, the FP-LD is applied to a 10 Gb/s DWDM system as a seed-light-source. In a local-seeding scheme, return-to zero (RZ) and carrier-suppressed (CS)-RZ signal formats are compared as a function of transmission distance. Furthermore, a back-reflection induced impairment is evaluated in a remote-seeding scheme. We also count the number of useable channels to show the feasibility of DWDM transmission. PMID- 27410603 TI - Compact highly-efficient polarization splitter and rotator based on 90 degrees bends. AB - We propose a compact highly-efficient CMOS-compatible polarization splitter and rotator (PSR) with a wide bandwidth covering the whole O-band. It benefits from the different confinement capability of TE and TM modes in bend structure. This bend structure helps shorten the PSR and maintain high efficiency, achieving the bending, polarization splitting, rotating of light beam at the same time. Numerical simulations utilizing Lumerical 3-D FDTD solutions demonstrate that the present PSR has a high TM-TE conversion efficiency of -0.11 dB and high TE-TE conversion efficiency of -0.09 dB at 1310 nm, while the extinction ratio is 27.36 dB and 30.61 dB respectively. PMID- 27410604 TI - Microresonator Brillouin laser stabilization using a microfabricated rubidium cell. AB - We frequency stabilize the output of a miniature stimulated Brillouin scattering (SBS) laser to rubidium atoms in a microfabricated cell to realize a laser system with frequency stability at the 10-11 level over seven decades in averaging time. In addition, our system has the advantages of robustness, low cost and the potential for integration that would lead to still further miniaturization. The SBS laser operating at 1560 nm exhibits a spectral linewidth of 820 Hz, but its frequency drifts over a few MHz on the 1 hour timescale. By locking the second harmonic of the SBS laser to the Rb reference, we reduce this drift by a factor of 103 to the level of a few kHz over the course of an hour. For our combined SBS and Rb laser system, we measure a frequency noise of 4 * 104 Hz2/Hz at 10 Hz offset frequency which rapidly rolls off to a level of 0.2 Hz2/Hz at 100 kHz offset. The corresponding Allan deviation is <=2 * 10-11 for averaging times spanning 10-4 to 103 s. By optically dividing the signal of the laser down to microwave frequencies, we generate an RF signal at 2 GHz with phase noise at the level of -76 dBc/Hz and -140 dBc/Hz at offset frequencies of 10 Hz and 10 kHz, respectively. PMID- 27410605 TI - Theoretical analysis of optical gain in uniaxial tensile strained and n+-doped Ge/GeSi quantum well. AB - The direct gap optical gain of [100] uniaxial tensile strained and n+ doped Ge/GeSi quantum well (QW) is calculated. The theoretical models for strained band structures near the Gamma- and L-point, optical gain and free carrier absorption are provided. Simulation results show that the optical gain can be dramatically enhanced with the help of uniaxial tensile strain and n-type doping. Furthermore, to consider the competition between gain and loss and get insight into the effects of strain and doping, the net peak gain and transparency carrier density at various strain value and doping concentration are evaluated. A net peak gain up to 2061 cm-1 for TE-polarized light is predicted at a strain value of 4%, a doping concentration of 1x1019 cm 3and an injected carrier density of 4x1019 cm-3. PMID- 27410606 TI - Trace analysis of oil-in-water by using visible LED and metal waveguide capillary. AB - Trace analysis of oil-in-water (O/W) has wide applications in life science, industry and environmental monitoring (such as oil spilling). In this paper, with the aid of surfactant, diesel was dispersed in water as O/W emulsion, which can be detected by using visible LED and metal-waveguide-capillary (MWC). Due to the enhancement of optical-path and related light-droplet interaction in MWC, detecting diesel of a concentration as low as 2.14 ng/ml was realized with a 7cm long MWC. The detection limit was improved 125 fold compared with that of commercial spectrophotometer with 1 cm-cuvette. The detecting system features compact, low cost and high sensitivity. PMID- 27410607 TI - Wide-range narrowband multilayer mirror for selecting a single-order harmonic in the photon energy range of 40-70 eV. AB - An experimental demonstration of a wide-range narrowband multilayer mirror for selecting a single-order high-harmonic (HH) beam from multiple-order harmonics in the photon energy range between 40 eV and 70 eV was carried out. This extreme ultraviolet (XUV) mirror, based on a pair of Zr and Al0.7Si0.3 multilayers, has a reflectivity of 20-35% and contrast of more than 7 with respect to neighboring HHs at angles of incidence from 10 to 56.9 degrees, assuming HHs pumped at 1.55 eV. Thus, specific single order harmonic beams can be arbitrarily selected from multiple-order harmonics in this photo energy range. In addition, the dispersion for input pulses of the order of 1 fs is negligible. This simple-to-align optical component is useful for the many various applications in physics, chemistry and biology that use ultrafast monochromatic HH beams. PMID- 27410608 TI - High-resolution, real-time simultaneous 3D surface geometry and temperature measurement. AB - This paper presents a method to simultaneously measure three-dimensional (3D) surface geometry and temperature in real time. Specifically, we developed 1) a holistic approach to calibrate both a structured light system and a thermal camera under exactly the same world coordinate system even though these two sensors do not share the same wavelength; and 2) a computational framework to determine the sub-pixel corresponding temperature for each 3D point as well as discard those occluded points. Since the thermal 2D imaging and 3D visible imaging systems do not share the same spectrum of light, they can perform sensing simultaneously in real time: we developed a hardware system that can achieve real time 3D geometry and temperature measurement at 26 Hz with 768 * 960 points per frame. PMID- 27410609 TI - Fast 3D reconstruction method for differential phase contrast X-ray CT. AB - We present a fast algorithm for fully 3D regularized X-ray tomography reconstruction for both traditional and differential phase contrast measurements. In many applications, it is critical to reduce the X-ray dose while producing high-quality reconstructions. Regularization is an excellent way to do this, but in the differential phase contrast case it is usually applied in a slice-by-slice manner. We propose using fully 3D regularization to improve the dose/quality trade-off beyond what is possible using slice-by-slice regularization. To make this computationally feasible, we show that the two computational bottlenecks of our iterative optimization process can be expressed as discrete convolutions; the resulting algorithms for computation of the X-ray adjoint and normal operator are fast and simple alternatives to regridding. We validate this algorithm on an analytical phantom as well as conventional CT and differential phase contrast measurements from two real objects. Compared to the slice-by-slice approach, our algorithm provides a more accurate reconstruction of the analytical phantom and better qualitative appearance on one of the two real datasets. PMID- 27410610 TI - Nonlinearity compensation and complex-to-phase conversion of complex incoherent digital holograms for optical reconstruction. AB - Incoherent digital holography (IDH) can be realized by optical scanning holography or self-interference incoherent holography. Although IDH can exhibit high quality reconstruction due to its inherently speckle-free property, direct display of an incoherent hologram is a challenge because of its amplitude nonlinearity and the demand of complex modulation. In this paper we propose to compensate the amplitude nonlinearity at the object plane, and use bidirectional error-diffusion method to convert the complex-type incoherent Fresnel hologram to a phase-only Fresnel hologram for display. A spatial light modulator is used to reconstruct the phase-only hologram optically to demonstrate the validity of our proposed method. PMID- 27410611 TI - Low-dissipation 7.4-um single-mode quantum cascade lasers without epitaxial regrowth. AB - We report continuous-wave operation of single-mode quantum cascade (QC) lasers emitting near 7.4 um with threshold power consumption below 1 W at temperatures up to 40 degrees C. The lasers were fabricated with narrow, plasma-etched waveguides and distributed-feedback sidewall gratings clad with sputtered aluminum nitride. In contrast to conventional buried-heterostructure (BH) devices with epitaxial sidewall cladding and in-plane gratings, the devices described here were fabricated without any epitaxial regrowth processes, yet they exhibit power consumption comparable to the lowest-dissipation BH QC lasers reported to date. These low-dissipation devices are designed primarily as light sources for infrared spectroscopy instruments with limited volume, mass, and power budgets. PMID- 27410613 TI - Antiphase domain tailoring for combination of modal and 4- -quasi-phase matching in gallium phosphide microdisks. AB - We propose a novel phase-matching scheme in GaP whispering-gallery-mode microdisks grown on Si substrate combining modal and 4- -quasi-phase-matching for second-harmonic-generation. The technique consists in unlocking parity-forbidden processes by tailoring the antiphase domain distribution in the GaP layer. Our proposal can be used to overcome the limitations of form birefringence phase matching and 4- -quasi-phase-matching using high order whispering-gallery-modes. The high frequency conversion efficiency of this new scheme demonstrates the competitiveness of nonlinear photonic devices monolithically integrated on silicon. PMID- 27410614 TI - Wireless multi-level terahertz amplitude modulator using active metamaterial based spatial light modulation. AB - The ever increasing demand for bandwidth in wireless communication systems will inevitably lead to the extension of operating frequencies toward the terahertz (THz) band known as the 'THz gap'. Towards closing this gap, we present a multi level amplitude shift keying (ASK) terahertz wireless communication system using terahertz spatial light modulators (SLM) instead of traditional voltage mode modulation, achieving higher spectral efficiency for high speed communication. The fundamental principle behind this higher efficiency is the conversion of a noisy voltage domain signal to a noise-free binary spatial pattern for effective amplitude modulation of a free-space THz carrier wave. Spatial modulation is achieved using an an active metamaterial array embedded with pseudomorphic high electron mobility (pHEMT) designed in a consumer-grade galium-arsenide (GaAs) integrated circuit process which enables electronic control of its THz transmissivity. Each array is assembled as individually controllable tiles for transmissive terahertz spatial modulation. Using the experimental data from our metamaterial based modulator, we show that a four-level ASK digital communication system has two orders of magnitude improvement in symbol error rate (SER) for a degradation of 20 dB in transmit signal-to-noise ratio (SNR) using spatial light modulation compared to voltage controlled modulation. PMID- 27410612 TI - Phasor plotting with frequency-domain flow cytometry. AB - Interest in time resolved flow cytometry is growing. In this paper, we collect time-resolved flow cytometry data and use it to create polar plots showing distributions that are a function of measured fluorescence decay rates from individual fluorescently-labeled cells and fluorescent microspheres. Phasor, or polar, graphics are commonly used in fluorescence lifetime imaging microscopy (FLIM). In FLIM measurements, the plotted points on a phasor graph represent the phase-shift and demodulation of the frequency-domain fluorescence signal collected by the imaging system for each image pixel. Here, we take a flow cytometry cell counting system, introduce into it frequency-domain optoelectronics, and process the data so that each point on a phasor plot represents the phase shift and demodulation of an individual cell or particle. In order to demonstrate the value of this technique, we show that phasor graphs can be used to discriminate among populations of (i) fluorescent microspheres, which are labeled with one fluorophore type; (ii) Chinese hamster ovary (CHO) cells labeled with one and two different fluorophore types; and (iii) Saccharomyces cerevisiae cells that express combinations of fluorescent proteins with different fluorescence lifetimes. The resulting phasor plots reveal differences in the fluorescence lifetimes within each sample and provide a distribution from which we can infer the number of cells expressing unique single or dual fluorescence lifetimes. These methods should facilitate analysis time resolved flow cytometry data to reveal complex fluorescence decay kinetics. PMID- 27410615 TI - Broadband optical transparency in plasmonic nanocomposite polymer films via exciton-plasmon energy transfer. AB - Inherent absorptive losses affect the performance of all plasmonic devices, limiting their fascinating applications in the visible range. Here, we report on the enhanced optical transparency obtained as a result of the broadband mitigation of optical losses in nanocomposite polymeric films, embedding core shell quantum dots (CdSe@ZnS QDs) and gold nanoparticles (Au-NPs). Exciton plasmon coupling enables non-radiative energy transfer processes from QDs to metal NPs, resulting in gain induced transparency of the hybrid flexible systems. Experimental evidences, such as fluorescence quenching and modifications of fluorescence lifetimes confirm the presence of this strong coupling between plexcitonic elements. Measures performed by means of an ultra-fast broadband pump probe setup demonstrate loss compensation of gold NPs dispersed in plastic network in presence of gain. Furthermore, we compare two films containing different concentrations of gold NPs and same amount of QDs, to investigate the role of acceptor concentration (Au-NPs) in order to promote an effective and efficient energy transfer mechanism. Gain induced transparency in bulk systems represents a promising path towards the realization of loss compensated plasmonic devices. PMID- 27410616 TI - Fusion splice between tapered inhibited coupling hypocycloid-core Kagome fiber and SMF. AB - We report for the first time on tapering inhibited coupling (IC) hypocycloid-core shape Kagome hollow-core photonic crystal fibers whilst maintaining their delicate core-contour negative curvature with a down-ratio as large as 2.4. The transmission loss of down-tapered sections reaches a figure as low as 0.07 dB at 1550 nm. The tapered IC fibers are also spliced to standard SMF with a total insertion loss of 0.48 dB. These results show that all-fiber photonic microcells with the ultra-low loss hypocycloid core-contour Kagome fibers is now possible. PMID- 27410617 TI - Topological properties of the interaction between focusing regions kind cusped. AB - We study here the cusped-cusped interaction between two kinds of Pearcey optical fields by analyzing its topological structure. We do it in two steps; the first one is an irradiance interaction that allows us to identify organization regions. The second one is an amplitude interaction, where it is shown that the interference fringes are organized around the irradiance distribution. The topological behavior of the optical field is analyzed identifying regions with different phase functions, one of them, corresponds with a catastrophe function which has associated a focusing region, the other region can be approximated by a quadratic function. The main consequence heritage from the phase structure is interference fringes emerge from focusing regions having similar features like a topological charges. We show computational and experimental results which are in very well agreement with the theoretical model. PMID- 27410619 TI - Numerical analysis of electrically tunable aspherical optofluidic lenses. AB - In this work, we use the numerical simulation platform Zemax to investigate the optical properties of electrically tunable aspherical liquid lenses, as we recently reported in an experimental study [ K. Mishra C. Murade B. Carreel I. Roghair J. M. Oh G. Manukyan D. van den Ende F. Mugele , "Optofluidic lens with tunable focal length and asphericity," Sci. Rep.4, 6378 (2014)]. Based on the measured lens profiles in the presence of an inhomogeneous electric field and the geometry of the optical device, we calculate the optical aberrations, focusing in particular on the Z11 Zernike coefficient of spherical aberration obtained at zero defocus (Z4). Focal length and spherical aberrations are calculated for a wide range of control parameters (fluid pressure and electric field), parallel with the experimental results. Similarly, the modulation transfer function (MTF), image spot diagrams, Strehl's ratio, and peak to-valley (P-V) and root mean square (RMS) wavefront errors are calculated to quantify the performance of our aspherical liquid lenses. We demonstrate that the device concept allows compensation for a wide range of spherical aberrations encountered in optical systems. PMID- 27410618 TI - Leaky wave lenses for spoof plasmon collimation. AB - We theoretically demonstrate the feasibility of collimating radiating spoof plasmons using a leaky wave lens approach. Spoof plasmons are surface waves excited along reactance surfaces realized through metallic corrugations. By employing a periodic perturbation to the geometric profile of this type of reactance surface, it becomes feasible to convert the excited spoof plasmons into free-space radiating leaky wave modes. It is demonstrated that by structurally modifying such a corrugated surface through the introduction of a non-uniform sinusoidally modulated reactance profile, then a tapered wavenumber, with a real part less than that of free space, can be established along the surface. In this way the radiating properties of the structure (amplitude and phase) can be locally controlled thereby creating a radiating effect similar to that of a non uniform current distribution. By properly engineering the space dependent wavenumber along the corrugated surface, different regions of the structure will emit spoof plasmon energy at different angles with varying intensity. The combined effect is the emission of an electromagnetic wave exhibiting a converging wave-front that eventually collimates spoof plasmon energy at some desired focal point. PMID- 27410620 TI - Periodic poling of Rb-doped KTiOPO4 by coercive field engineering. AB - We demonstrate fine-pitch periodic poling of bulk Rb-doped KTiOPO4 using a coercive field grating induced by ion-exchange. These samples were used for quasi phase matched (QPM) second harmonic generation at 795 nm with a normalized conversion efficiency of 1.7% W-1cm-1. Additionally, the ion-exchange introduced a refractive index change over the sample thickness resulting in a phasematching wavelength shift of 0.21 nm, adding extra tunability to the QPM device. PMID- 27410621 TI - In-fiber Fabry-Perot interferometer for strain and magnetic field sensing. AB - In this paper we discuss the results obtained with an in-fiber Fabry-Perot interferometer (FPI) used in strain and magnetic field (or force) sensing. The intrinsic FPI was constructed by splicing a small section of a capillary optical fiber between two pieces of standard telecommunication fiber. The sensor was built by attaching the FPI to a magnetostrictive alloy in one configuration and also by attaching the FPI to a small magnet in another. Our sensors were found to be over 4 times more sensitive to magnetic fields and around 10 times less sensitive to temperature when compared to sensors constructed with Fiber Bragg Grating (FBG). PMID- 27410622 TI - Subwavelength three-dimensional frequency selective surface based on surface wave tunneling. AB - We propose a new type of three-dimensional frequency selective structure (3D-FSS) in form of subwavelength staggered metallic frames, and demonstrate a new design concept of confining and guiding surface wave propagation through the transmission tunnels for spacial filters. Both qualitative analysis by current loops and full-wave simulations show that the strong coupling along metallic frames can enhance the performance of frequency response, such as a sharper roll off, clean out-of-band rejection, as well as angle and polarization insensitivity. Moreover, different unit cell shapes are introduced to confirm the universality of the design concept. Finally, a 3D-FSS with staggered rectangular frames was realized by experiment. PMID- 27410623 TI - Electronically tunable thulium-holmium mode-locked fiber laser for the 1700-1800 nm wavelength band. AB - We demonstrate a widely tunable, mode-locked fiber laser capable of producing sub picosecond pulses between 1705 and 1805 nm. The 100 nm tuning range is achieved by using intracavity acousto-optic tunable filter. The laser delivers highly stable pulses via self-starting hybrid mode-locking triggered by frequency shifting and nonlinear polarization evolution. PMID- 27410624 TI - Q-switched-like soliton bunches and noise-like pulses generation in a partially mode-locked fiber laser. AB - We report an intermediate regime between c.w. emission and noise-like pulses (NLPs) regime in an Er-doped partially mode-locked fiber laser with nonlinear polarization rotation. In this regime, the soliton bunches stochastically turn up from a quasi-cw background in the Q-switched-like envelope. The soliton bunches normally last for tens or hundreds of intracavity round-trips. When the soliton bunches vanish, typical NLPs chains are generated sporadically at location where the soliton bunches collapses. These results would be helpful to understand the generation and property of the NLPs regime. PMID- 27410625 TI - Mid-infrared supercontinuum generation based on cascaded Raman scattering in a few-mode As2S3 fiber pumped by a thulium-doped fiber laser. AB - By pumping a 1.7-m-long As2S3 fiber at 2050 nm directly, a fiber-based mid-infrared supercontinuum (SC) source with an output power of 366 mW is demonstrated. This is the first experimental demonstration to obtain such a mid-infrared SC in a piece of chalcogenide fiber pumped at 2 MUm directly. The cut-off wavelength of the As2S3 fiber is 3.5 MUm, indicating that it could support several modes at around 2 MUm. It is found that nonlinear spectral broadening mechanisms in the few-mode chalcogenide fiber could be affected through adjusting the butt-coupling position. That is because different positions will excite different modes that correspondingly possess different nonlinearity and dispersion characteristics. When stimulated Raman scattering (SRS) corresponding to the excitation of the fundamental mode becomes dominant in this few-mode fiber, an efficient cascaded SRS-based SC is obtained with five Stokes peaks ranging from 2 MUm to 3.4 MUm. Results from numerical simulation are in accord with the experimental results, showing that it is feasible to obtain an SRS based mid-infrared SC in a step-index As2S3 fiber by using a 2 MUm high peak power picosecond laser to pump directly. PMID- 27410626 TI - Waveguide Bragg gratings in Ormocer hybrid polymers. AB - We report on the fabrication of Bragg gratings within rib-type waveguides of previously UV-cured inorganic-organic Ormocer hybrid polymers by applying the interferometric phase mask technique in conjunction with deep-UV laser radiation. The fabrication process as well as the influence of the applied laser fluence and the length of the Bragg grating on the characteristics of the Bragg grating's transmission and reflection spectra are discussed and compared to numerical simulations and calculations. Depending on the applied laser fluence and the chosen grating length, waveguide Bragg gratings with strong reflectivities of up to 98 % and narrow bandwidths of down to 120 pm have been achieved. PMID- 27410627 TI - Intrinsic coincident linear polarimetry using stacked organic photovoltaics. AB - Polarimetry has widespread applications within atmospheric sensing, telecommunications, biomedical imaging, and target detection. Several existing methods of imaging polarimetry trade off the sensor's spatial resolution for polarimetric resolution, and often have some form of spatial registration error. To mitigate these issues, we have developed a system using oriented polymer-based organic photovoltaics (OPVs) that can preferentially absorb linearly polarized light. Additionally, the OPV cells can be made semitransparent, enabling multiple detectors to be cascaded along the same optical axis. Since each device performs a partial polarization measurement of the same incident beam, high temporal resolution is maintained with the potential for inherent spatial registration. In this paper, a Mueller matrix model of the stacked OPV design is provided. Based on this model, a calibration technique is developed and presented. This calibration technique and model are validated with experimental data, taken with a cascaded three cell OPV Stokes polarimeter, capable of measuring incident linear polarization states. Our results indicate polarization measurement error of 1.2% RMS and an average absolute radiometric accuracy of 2.2% for the demonstrated polarimeter. PMID- 27410628 TI - Fast gridding projectors for analytical and iterative tomographic reconstruction of differential phase contrast data. AB - This paper introduces new gridding projectors designed to efficiently perform analytical and iterative tomographic reconstruction, when the forward model is represented by the derivative of the Radon transform. This inverse problem is tightly connected with an emerging X-ray tube- and synchrotron-based imaging technique: differential phase contrast based on a grating interferometer. This study shows, that the proposed projectors, compared to space-based implementations of the same operators, yield high quality analytical and iterative reconstructions, while improving the computational efficiency by few orders of magnitude. PMID- 27410629 TI - Enhanced plasmonic nanofocusing of terahertz waves in tapered graphene multilayers. AB - We investigate the plasmonic nanofocusing of terahertz waves in tapered graphene multilayers separated by dielectrics. The nanofocusing effect is significantly enhanced in the graphene multilayer taper compared with that in a single layer graphene taper due to interlayer coupling between surface plasmon polaritons. The results are optimized by choosing an appropriate layer number of graphene and the field amplitude has been enhanced by 620 folds at lambda = 50 MUm. Additionally, the structure can slow light to a group velocity ~1/2815 of the light speed in vacuum. Our study provides a unique approach to compress terahertz waves into deep subwavelength scale and may find great applications in terahertz nanodevices for imaging, detecting and spectroscopy. PMID- 27410630 TI - Enhanced photoacoustics from gold nano-colloidal suspensions under femtosecond laser excitation. AB - Enhanced photoacoustic (PA) intensity from gold nanosphere and nanorod colloidal suspensions in water under tightly-focused femtosecond pulsed laser irradiation was systematically investigated. PA signal amplitudes were measured by ultrasound transducers at frequencies of 5, 10, and 25 MHz. The experimental results revealed a linear-dependence of the relative photoacoustic amplitude on the laser power and the mechanism was attributed to non-radiative relaxation dynamics of surface plasmon oscillations. When gold nanorod with longitudinal absorption/extinction peak at 800 nm coincides with the wavelength of femtosecond laser pulses, the most efficient PA signal is generated. Laser excitation was kept within a thermal stability region of gold nanoparticles, i.e., colloidal suspension can be continuously reused for PA generation. PMID- 27410631 TI - Hysteresis-free and submillisecond-response polymer network liquid crystal. AB - We demonstrate a polymer network liquid crystal (PNLC) with negligible hysteresis while keeping submillisecond response time. By doping about 1% dodecyl acrylate (C12A) into the liquid crystal/monomer precursor, both hysteresis and residual birefringence are almost completely eliminated. The operating voltage and scattering properties remain nearly intact, but the tradeoff is enhanced double relaxation. This hysteresis-free PNLC should find applications in spatial light modulators, laser beam control, and optical communications in infrared region. PMID- 27410632 TI - Bending loss characterization in nodeless hollow-core anti-resonant fiber. AB - We report high performance nodeless hollow-core anti-resonant fibers (HARFs) with broadband guidance from 850 nm to >1700 nm and transmission attenuation of ~100 dB/km. We systematically investigate their bending loss behaviors using both theoretical and experimental approaches. While a low bending loss value of 0.2 dB/m at 5 cm bending radius is attained in the long wavelength side (LWS) of the spectrum, in this paper, we pursue light guidance in the short wavelength side (SWS) under tight bending, which is yet to be explored. We analytically predict and experimentally verify a sub transmission band in the SWS with a broad bandwidth of 110 THz and an acceptable loss of 4.5 dB/m at 2 cm bending radius, indicating that light can be simultaneously guided in LWS and SWS even under tight bending condition. This provides an unprecedented degree of freedom to tailor the transmission spectrum under a tight bending state and opens new opportunities for HARFs to march into practical applications where broadband guidance under small bending radius is a prerequisite. PMID- 27410633 TI - Simultaneous even- and third-order distortion suppression in a microwave photonic link based on orthogonal polarization modulation, balanced detection, and optical sideband filtering. AB - A microwave photonic link (MPL) with simultaneous suppression of the even-order and third-order distortions using a polarization modulator (PolM), an optical bandpass filter (OBPF), and a balanced photodetector (BPD) is proposed and experimentally demonstrated. The even-order distortions are suppressed by utilizing orthogonal polarization modulation based on the PolM and balanced differential detection based on the BPD. The third-order distortions (IMD3) are suppressed by optimizing the spectral response of the OBPF with an optimal power ratio between the optical carrier and the sidebands of the phase-modulated signals from the PolM. Since the suppression of the IMD3 is achieved when the MPL is optimized for even-order distortion suppression, the proposed MPL can operate with simultaneous suppression of the even-order and third-order distortions. The proposed MPL is analyzed theoretically and is verified by an experiment. For a two-tone RF signal of f1 = 10 GHz and f2 = 19.95 GHz, the spurious-free dynamic range (SFDR2) is enhanced by 23.4 dB for the second harmonic (2f1), and 29.1 and 27.6 dB for the second intermodulation (f2-f1 and f1 + f2), as compared with a conventional MPL. For a two-tone RF signal of f1 = 9.95 GHz and f2 = 10 GHz, the SFDR3 is increased by 13.1 dB as compared with a conventional MPL. PMID- 27410634 TI - Generation of 0.19-mJ THz pulses in LiNbO3 driven by 800-nm femtosecond laser. AB - A cylindrical lens telescope tilted-pulse-front pumping scheme was proposed for high energy terahertz (THz) pulse generation. This scheme allows higher pump energy to be used with lower saturation effects under high pump fluence, and higher THz generation efficiency was achieved within large range of pump energy. The optimum pump pulse duration and crystal cooling temperature for THz generation in LiNbO3 (LN) crystal were also researched systematically. Excited by 800-nm laser, up to 0.19 mJ THz pulse energy and 0.27% conversion efficiency was demonstrated under 800-nm 400-fs laser excitation with ~100-mJ pulse energy and 150-K LN cooling temperature. PMID- 27410635 TI - Femtosecond Kerr-lens mode-locked Alexandrite laser. AB - The generation of 170 fs pulses at 755 nm from a Kerr-lens mode-locked Alexandrite laser was demonstrated. The laser was pumped at 532 nm and produced 780 mW of average output power with 9.8% of optical-to-optical efficiency. To the best of our knowledge, these are the shortest pulses that have been produced from a mode-locked Alexandrite laser to date. PMID- 27410636 TI - Switchable in-line monitor for multi-dimensional multiplexed photonic integrated circuit. AB - A flexible monitor suitable for the discrimination of on-chip transmitted mode division multiplexed (MDM) and wavelength division multiplexed (WDM) signals is proposed and fabricated. By selectively extracting part of the incoming signals through the tunable wavelength and mode dependent drop filter, the in-line and switchable monitor can discriminate the wavelength, mode and power information of the transmitted signals. Being different from a conventional mode and wavelength demultiplexer, the monitor is specifically designed to ensure a flexible in-line monitoring. For demonstration, three mode and three wavelength multiplexed signals are successfully processed. Assisted by the integrated photodetectors (PDs), both the measured photo currents and eye diagrams validate the performance of the proposed device. The bit error ratio (BER) measurement results show less than 0.4 dB power penalty between different modes and ~2 dB power penalty for single wavelength and WDM cases under 10-9 BER level. PMID- 27410637 TI - Detectability of active triangulation range finder: a solar irradiance approach. AB - Active triangulation range finders are widely used in a variety of applications such as robotics and assistive technologies. The power of the laser source should be carefully selected in order to satisfy detectability and still remain eye safe. In this paper, we present a systematic approach to assess the detectability of an active triangulation range finder in an outdoor environment. For the first time, we accurately quantify the background noise of a laser system due to solar irradiance by coupling the Perez all-weather sky model and ray tracing techniques. The model is validated with measurements with a modeling error of less than 14.0%. Being highly generic and sufficiently flexible, the proposed model serves as a guide to define a laser system for any geographical location and microclimate. PMID- 27410638 TI - Conical third-harmonic generation of optical vortex through ultrashort laser filamentation in air. AB - We experimentally generate third-harmonic (TH) vortex beams in air by the filamentation of femtosecond pulses produced in a lab-built Ti:sapphire chirped pulse amplifier. The generated TH beam profile is shown to evolve with increasing pump energy. At a sufficiently high pump energy, we observe a conical TH emission of the fundamental vortex and confirm that the conical radiation follows the conservation law for orbital angular momentum. We further investigate the far field angularly resolved spectra of the TH wave to analyze the conical emission angle. We theoretically verify that the formation of the conical TH vortex results from the phase-matching between the fundamental and TH waves during the filamentation process. PMID- 27410639 TI - Influence of a backward reflection on low-threshold mode instability in Yb3+-doped few-mode fiber amplifiers. AB - An influence of backward reflection on spatio-temporal instability of the fundamental mode in Yb3+-doped few-mode polarization maintaining fiber amplifiers with a core diameter of 10 MUm was studied experimentally and theoretically. The mode instability threshold was registered to decrease dramatically in the presence of a backward reflection of the signal from the output fiber end; an increase of the signal bandwidth or input power resulted in the increase of the threshold. Numerical simulation revealed a self-consistent growth of the higher-order mode LP11 and a traveling index grating accompanying the population grating induced by the mode interference field (due to different polarizability of the excited and unexcited Yb3+ ions). The presence of the backward-propagating wave resulted in four-wave mixing on the common index grating induced by the interference field of pairs of the fundamental LP01 and LP11 modes. PMID- 27410640 TI - Universal nonlinear scattering in ultra-high Q whispering gallery-mode resonators. AB - Universal nonlinear scattering processes such as Brillouin, Raman, and Kerr effects are fundamental light-matter interactions of particular theoretical and experimental importance. They originate from the interaction of a laser field with an optical medium at the lattice, molecular, and electronic scale, respectively. These nonlinear effects are generally observed and analyzed separately, because they do not often occur concomitantly. In this article, we report the simultaneous excitation of these three fundamental interactions in mm size ultra-high Q whispering gallery mode resonators under continuous wave pumping. Universal nonlinear scattering is demonstrated in barium fluoride and strontium fluoride, separately. We further propose a unified theory based on a spatiotemporal formalism for the understanding of this phenomenology. PMID- 27410641 TI - Upconversion in a Bragg structure: photonic effects of a modified local density of states and irradiance on luminescence and upconversion quantum yield. AB - In this paper, we present a comprehensive simulation-based analysis of the two photonic effects of a Bragg stack - a modified local density of photon states (LDOS) and an enhanced local irradiance - on the upconversion (UC) luminescence and quantum yield of the upconverter beta-NaYF4 doped with 25% Er3+. The investigated Bragg stack consists of alternating layers of TiO2 and Poly(methylmethacrylate), the latter containing upconverter nanoparticles. Using experimentally determined input parameters, the photonic effects are first simulated separately and subsequently coupled in a rate equation model, describing the dynamics of the UC processes within beta NaYF4:25% Er3+. With this integrated simulation model, the Bragg stack design is optimized to maximize either the UC quantum yield (UCQY) or UC luminescence. We find that in an optimized Bragg stack, due to the modified LDOS, the maximum UCQY is enhanced from 14% to 16%, compared to an unstructured layer of upconverter material. Additionally, this maximum UCQY can already be reached at an incident irradiance as low as 100 W/m2. With a Bragg stack design that maximizes UC luminescence, enhancement factors of up to 480 of the UC luminescence can be reached. PMID- 27410642 TI - Parameter optimization for through-focus scanning optical microscopy. AB - It is important to economically and non-destructively analyze three-dimensional (3-D) shapes of nanometer to micrometer scale objects with sub-nanometer measurement resolution for emerging high-volume nanomanufacturing, especially for process control. High-throughput through-focus scanning optical microscopy (TSOM) demonstrates promise for such applications. TSOM uses a conventional optical microscope for 3-D shape metrology by making use of the complete set of through focus, four-dimensional optical data. However, a systematic study showing the effect of various parameters on the TSOM method is lacking. Here we present the optimization of the basic parameters such as illumination numerical aperture (NA), collection NA, focus step height, digital camera pixel size, illumination polarization, and illumination wavelength to achieve peak performance of the TSOM method. PMID- 27410643 TI - Analysis of excited-state Faraday anomalous dispersion optical filter at 1529 nm. AB - In this work, a detailed theoretical analysis of 1529 nm ES-FADOF (excited state Faraday anomalous dispersion optical filter) based on rubidium atoms pumped by 780 nm laser is introduced, where Zeeman splitting, Doppler broadening, and relaxation processes are considered. Experimental results are carefully compared with the derivation. The results prove that the optimal pumping frequency is affected by the working magnetic field. The population distribution among all hyperfine Zeeman sublevels under the optimal pumping frequency has also been obtained, which shows that 85Rb atoms are the main contribution to the population. The peak transmittance above 90% is obtained, which is in accordance with the experiment. The calculation also shows that the asymmetric spectra observed in the experiment are caused by the unbalanced population distribution among Zeeman sublevels. This theoretical model can be used for all kinds of calculations for FADOF. PMID- 27410644 TI - Improved method for skin reflectance reconstruction from camera images. AB - A improved spectral reflectance reconstruction method is developed to transform camera RGB to spectral reflectance for skin images. Rather than using conventional direct or two-step processes, we transform camera RGB to skin reflectance directly using a principal component analysis (PCA) approach. The novelty in our direct method (RGB to spectra) is the use of a skin-specific colour characterisation chart with spectra closer to human skin spectra, and a new database of skin reflectances to derive the PCA bases. The experimental results using the facial images of 17 subjects demonstrate that our new direct method gives a significantly better performance than conventional, two-step methods and direct methods with traditional characterization charts. This new spectral reconstruction algorithm is sufficiently precise to reconstruct spectral properites relating to chromophores and its performance is within the acceptable range for maxillofacial soft tissue prostheses (error < 3 DeltaE*ab units). PMID- 27410645 TI - Square dielectric THz waveguides. AB - A holey cladding dielectric waveguide with square cross section is designed, simulated, fabricated and characterized. The TOPAS waveguide is designed to be single mode across the broad frequency range of 180 GHz to 360 GHz as shown by finite-difference time domain simulation and to robustly support simultaneous TE and TM mode propagation. The square fiber geometry is realized by pulling through a heat distribution made square by appropriate furnace design. The transmitted mode profile is imaged using a vector network analyzer with a pinhole at the receiver module. Good agreement between the measured mode distribution and the calculated mode distribution is demonstrated. PMID- 27410646 TI - 1% rms amplitude noise from a 30 fs continuum based source tunable from 800 to 1250 nm. AB - We present amplitude noise characterization of a low-cost continuum source tunable from 800 to 1250 nm, with the pulse duration of 30 fs, and average output power up to 140 mW at 80 MHz pulse repetition rate. The system is based on a SESAM-modelocked, solid-state Yb tungstate laser plus spectral broadening via a microstructured fiber followed by pulse compression with a simple prism compressor. The measured RMS amplitude noise of 1.2 to 2.5% in the whole tunable range is comparable to the modelocked oscillators. Additionally, we show an excellent agreement between simulated and the experimentally measured spectra. PMID- 27410647 TI - Stable high-power Er:YAG ceramic single-frequency laser at 1645 nm. AB - A stable high-power single-frequency laser at 1645 nm from a monolithic Er:YAG ceramic nonplanar ring oscillator (NPRO) was demonstrated. 10.7 W single frequency laser output was obtained with a slope efficiency of 61.2% and an optical efficiency of 52.1% with respect to incident pump power. The laser always stably operated in single-frequency mode with the pump power increasing from threshold to maximum pump power. When the crystal's set temperature changed from 17.2 degrees C to 26.6 degrees C, the Er:YAG ceramic NPRO had stable single frequency laser output, and the widest continuous tuning range without mode hoping was 4.5 GHz. The linewidth of the single-frequency laser was 5.75 kHz. The beam quality M2 factors were 1.23 and 1.24 in x and y directions, respectively. PMID- 27410648 TI - Two-dimensional grating for narrow-band filtering with large angular tolerances. AB - A two-dimensional periodic sub-wavelength array of vertical dielectric cylinders on a glass substrate is studied numerically using three different electromagnetic approaches. It is shown that such structure can present a narrow-band spectral resonance characterized by large angular tolerances and 100% maximum in reflection. In particular, in a two-nanometer spectral bandwidth the reflectivity stays above 90% within angles of incidence exceeding 10 degrees for unpolarized light. Bloch modal analysis shows that these properties are due to the excitation of a hybrid mode that is created in the structure by a guided-like mode and a localized cavity mode. The first one is due to the collective effect of the array, while the second one comes from the mode(s) of a single step-index fiber. PMID- 27410649 TI - Dual optical frequency comb architecture with capabilities from visible to mid infrared. AB - In this paper, a new approach to dual comb generation based on well-known optical techniques (Gain-Switching and Optical Injection Locking) is presented. The architecture can be implemented using virtually every kind of continuous-wave semiconductor laser source (DFB, VCSEL, QCL) and without the necessity of electro optic modulators. This way, a frequency-agile and adaptive dual-comb architecture is provided with potential implementation capabilities from mid-infrared to near ultraviolet. With a RF comb comprising around 70 teeth, the system is validated in the 1.5 MUm region measuring the absorption feature of H13CN at 1538.523 nm with a minimum integration time of 10 MUs. PMID- 27410651 TI - High-power linearly-polarized picosecond thulium-doped all-fiber master oscillator power-amplifier. AB - We demonstrated a linearly-polarized picosecond thulium-doped all-fiber integrated master-oscillator power-amplifier system, which yielded 240 W of average output power at 127 MHz repetition rate. The seed source is a passively mode-locked polarization-maintaining thulium-doped all-fiber oscillator with a nearly transform-limited pulse duration of 10 ps. In combination with a pre-chirp fiber having a positive group velocity dispersion and a three stage polarization maintaining thulium-doped all-fiber amplifier, output pulse energies up to 1.89 uJ with 42 kW pulse peak power are obtained without the need of complex free space stretcher or compressor setups. To the best of our knowledge, this is the highest average output power ever reported for a picosecond all-fiber-integrated laser at 2 um wavelength region. PMID- 27410650 TI - Signal interference RF photonic bandstop filter. AB - In the microwave domain, signal interference bandstop filters with high extinction and wide stopbands are achieved through destructive interference of two signals. Implementation of this filtering concept using RF photonics will lead to unique filters with high performance, enhanced tuning range and reconfigurability. Here we demonstrate an RF photonic signal interference filter, achieved through the combination of precise synthesis of stimulated Brillouin scattering (SBS) loss with advanced phase and amplitude tailoring of RF modulation sidebands. We achieve a square-shaped, 20-dB extinction RF photonic filter over a tunable bandwidth of up to 1 GHz with a central frequency tuning range of 16 GHz using a low SBS loss of ~3 dB. Wideband destructive interference in this novel filter leads to the decoupling of the filter suppression from its bandwidth and shape factor. This allows the creation of a filter with all optimized qualities. PMID- 27410652 TI - 7kW direct-liquid-cooled side-pumped Nd:YAG multi-disk laser resonator. AB - A direct-liquid-cooled side-pumped Nd:YAG multi-disk QCW laser resonator is presented, in which the oscillating laser propagates through multiple thin disks and cooling flow layers in Brewster angle. Twenty Nd:YAG thin disks side-pumped by LD arrays are directly cooled by flowing deuteroxide at the end surfaces. A laser output with the highest pulse energy of 17.04 J is obtained at the pulse width of 250 MUs and repetition rate of 25 Hz, corresponding to an optical optical efficiency of 34.1% and a slope efficiency of 44.5%. The maximum average output power of 7.48 kW is achieved at the repetition rate of 500 Hz. Due to thermal effects, the corresponding optical-optical efficiency decreases to 30%. Under the 12.5 kW pumping condition while not oscillating, the wavefront of a He Ne probe passing through the gain module is as low as 0.256 MUm (RMS) with the defocus and tetrafoil subtracted. PMID- 27410653 TI - Plasmonic Archimedean spiral modes on concentric metal ring gratings. AB - Plasmonic Archimedean spiral modes on concentric silver (Ag) ring gratings are investigated by FDTD simulations and theoretical analyses. These modes are generated by placing the ring grating under an Ag nanorod to extract the orbital angular momentum (OAM) of spiral surface plasmon (SSP) modes on the nanorod and transform it into the orbital motion of SP on the grating. The formation of Archimedean spiral patterns is ascribed to two factors: both the r- and theta directional wavevectors are conserved for SSP on nanorod coupling into SP on ring grating and both the r- and theta-directional velocities of SP keep unchanged when it propagates on the ring grating. The number of strands of Archimedean spiral pattern is determined by the topological charge of SSP mode. The plasmonic Archimedean spiral modes have potential applications in the fields of data storage, dielectric microparticle manipulation, biosensing and directional switching. PMID- 27410654 TI - Volumetric HiLo microscopy employing an electrically tunable lens. AB - Electrically tunable lenses exhibit strong potential for fast motion-free axial scanning in a variety of microscopes. However, they also lead to a degradation of the achievable resolution because of aberrations and misalignment between illumination and detection optics that are induced by the scan itself. Additionally, the typically nonlinear relation between actuation voltage and axial displacement leads to over- or under-sampled frame acquisition in most microscopic techniques because of their static depth-of-field. To overcome these limitations, we present an Adaptive-Lens-High-and-Low-frequency (AL-HiLo) microscope that enables volumetric measurements employing an electrically tunable lens. By using speckle-patterned illumination, we ensure stability against aberrations of the electrically tunable lens. Its depth-of-field can be adjusted a-posteriori and hence enables to create flexible scans, which compensates for irregular axial measurement positions. The adaptive HiLo microscope provides an axial scanning range of 1 mm with an axial resolution of about 4 MUm and sub micron lateral resolution over the full scanning range. Proof of concept measurements at home-built specimens as well as zebrafish embryos with reporter gene-driven fluorescence in the thyroid gland are shown. PMID- 27410655 TI - Manipulating radiation beams by symmetry of magnetic photonic crystals. AB - We theoretically and experimentally study the radiation of current line source embedded in two-dimensional photonic crystals (PCs) made of ferrite rods. Depending on the symmetry of the PCs, the source radiation working at the band edge of the PCs can be multiple or single beam radiation with narrow beam width. Different ways to change the PC symmetry are proposed. Taking advantage of tunable bandgap of the magnetic PC and by lowering the symmetry of the PC, the radiation direction and its working frequency can be reconfigured by bias magnetic field. Experiments demonstrate the dependence of radiation on the PC symmetry. PMID- 27410656 TI - Detailed numerical analysis of photon emission from a single light emitter coupled with a nanofiber Bragg cavity. AB - Coupling of a single dipole with a nanofiber Bragg cavity (NFBC) approximating an actually fabricated structure was numerically analyzed using three dimensional finite-difference time-domain simulations for different dipole positions. For the given model structure, the Purcell factor and coupling efficiency reached to 19.1 and 82%, respectively, when the dipole is placed outside the surface of the fiber. Interestingly, these values are very close to the highest values of 20.2 and 84% obtained for the case when the dipole was located inside the fiber at the center. The analysis performed in this study will be useful in improving the performance of single-photon emitter-related quantum devices using NFBCs. PMID- 27410657 TI - Reflectance difference spectroscopy microscope for circular defects on InN films. AB - Reflectance difference spectroscopy microscope (MU-RDS) is presented to characterize microstructural defects on the surface of materials. We use this microscope to study the circular defects on InN films and obtain the real normal reflectivity image and reflectance difference (RD) image by averaging the results before and after a 90 degrees rotation of the sample. We analyze the experimental data along with other methods and formally ensure the reliability of this microscope. Comparing with the results of AFM, we prove that the reflectivity image of our MU-RDS can characterize the surface topography, size and location of the defects. We find the RD image generated by uniform height fluctuation is a standard four polar distribution in an established ideal circular defect model. However, a non-four polar distribution of RD image can be caused by the strain field as well as nonstandard height fluctuations, which is verified by simulation and Raman mapping technique. So the MU-RDS is an ideal tool for optical anisotropy distribution induced by small changes in the height and strain field around the defect boundary in plane. PMID- 27410658 TI - Highly pure green light emission of perovskite CsPbBr3 quantum dots and their application for green light-emitting diodes. AB - All-inorganic perovskite CsPbBr3 quantum dots (QDs) with an emission peak of around 520 nm were synthesized by a hot-injection method, and were systematically studied as green phosphor for light-emitting diodes (LEDs). Highly pure green light with an emission peak of 534 nm and a full-width at half-maximum (FWHM) about 20 nm was achieved using CsPbBr3 QDs and GaN LEDs. Commission Internationale Ed I'Eclairage coordinate of the fabricated green LEDs was (0.203, 0.757). Compared to GaN LEDs, the current-voltage characteristic of the green LED did not show any degradation. Moreover, the green LEDs displayed a luminous efficiency of 31.92 lm/W under an injection current of 10 mA. PMID- 27410659 TI - Wideband multilayer gratings for the 17-25 nm spectral region. AB - An approach to designing wideband blazed multilayer gratings is introduced and applied to gratings operating at 17-25 nm. We demonstrate single-order operation of broadband multilayer gratings, despite their very wide spectral and angular bandpass, when only one diffraction wave is excited and the diffraction efficiency reaches the reflectivity of a conventional depth-graded multilayer mirror, eliminating overlapping of different-order diffraction waves. The selection principles for the geometrical parameters of gratings are discussed. We formulate a "law of similarity" for wideband gratings that allows us to design gratings with different geometrical parameters but practically the same spectral dependence of the diffraction efficiency. PMID- 27410660 TI - Mid-infrared supercontinuum generation in step-index As2S3 fibers pumped by a nanosecond shortwave-infrared supercontinuum pump source. AB - A supercontinuum (SC) source spanning from 2 to 4 MUm is demonstrated in As2S3-chalcogenide fibers pumped by a nanosecond supercontinuum pump source in the normal dispersion region. In this experiment, two pieces of 3-m-long step-index As2S3 fiber with different core diameters of 7 MUm and 9 MUm are pumped by a 1.9-2.5 MUm nanosecond supercontinuum source. The zero dispersion wavelengths are both beyond 6.6 MUm, thus cascaded stimulated Raman scattering is believed to be the dominant mechanism responsible for spectral broadening. With a low peak pump power of ~2.9 kW, both of the output spectra have extended to 4 MUm with enhanced power distribution in the MIR region. The maximum output power of the mid-infrared supercontinua is ~140 mW. To the best of our knowledge, it is the first supercontinuum extenting to 4 MUm in an As2S3 fiber pumped by shortwave-infrared SC pluses in the normal dispersion region. PMID- 27410661 TI - High-Q mid-infrared thermal emitters operating with high power-utilization efficiency. AB - We demonstrate a single-mode high-Q (Q>100) mid-infrared thermal emitter operating with high power-utilization efficiency. The emitter consists of a rod type photonic crystal (PC) slab interacting with GaAs/AlGaAs multiple quantum wells (MQWs), a GaAs substrate frame supporting the PC slab, and electric wires for Joule heating of the device. We carefully design the structure of the PC slab and the supporting frame/wires to minimize unwanted thermal losses and realize narrowband thermal emission having a peak intensity, under a given electrical input power, that is an order of magnitude higher than that of a reference blackbody emitter due to the efficient increase of the device temperature. PMID- 27410662 TI - Numerical investigation of enhanced femtosecond supercontinuum via a weak seed in noble gases. AB - Numerical simulations are employed to elucidate the physics underlying the enhanced femtosecond supercontinuum generation previously observed during optical filamentation in noble gases and in the presence of a weak seed pulse. Simulations based on the metastable electronic state approach are shown not only to capture the qualitative features of the experiment, but also reveal the relation of the observed enhancement to recent developments in the area of sub cycle engineering of filaments. PMID- 27410663 TI - Cavity-resonator-integrated guided-mode resonance band-stop reflector. AB - A cavity-resonator-integrated guided-mode resonance filter (CRIGF) consists of a grating coupler inside a pair of distributed Bragg reflectors. A combination of a CRIGF with a high-reflection substrate can provide a new type of a band-stop reflector with a small aperture for a vertically incident wave from air. A narrow stopband was theoretically predicted and experimentally demonstrated. It was quantitatively shown that reflection spectra depended on optical-buffer-layer thickness. The reflector of 10-MUm aperture was fabricated and characterized. The extinction ratio in reflectance was measured to be lower than -20 dB at a resonance wavelength. The bandwidth at -3 dB was 0.15 nm. PMID- 27410664 TI - Transmission of independent signals through a multimode fiber using digital optical phase conjugation. AB - Multimode fibers are attractive for a variety of applications such as communication engineering and biophotonics. However, a major hurdle for the optical transmission through multimode fibers is the inherent mode mixing. Although an image transmission was successfully accomplished using wavefront shaping, the image information was not transmitted individually for each of the independent pixels. We demonstrate a transmission of independent signals using individually shaped wavefronts employing a single segmented spatial light modulator for optical phase conjugation regarding each light signal. Our findings pave the way towards transferring independent signals through strongly scattering media. PMID- 27410665 TI - Pseudo-type-II tuning behavior and mode identification in whispering gallery optical parametric oscillators. AB - Wavelength tuning of conventional mirror-based optical parametric oscillators (OPOs) exhibits parabolically-shaped tuning curves (type-0 and type-I phase matching) or tuning branches that cross each other with a finite slope (type-II phase matching). We predict and experimentally prove that whispering gallery OPOs based on type-0 phase matching show both tuning behaviors, depending on whether the mode numbers of the generated waves coincide or differ. We investigate the wavelength tuning of optical parametric oscillation in a millimeter-sized radially-poled lithium niobate disk pumped at 1 MUm wavelength generating signal and idler waves between 1.7 and 2.6 MUm wavelength. Our experimental findings excellently coincide with the theoretical predictions. The investigated whispering gallery optical parametric oscillator combines the employment of the highest nonlinear-optical coefficient of the material with a controlled type-II like wavelength tuning and with the possibility of self-phase locking. PMID- 27410666 TI - High-dimensional encoding based on classical nonseparability. AB - Based on the formal analogy between classical nonseparability and quantum entanglement, we present a multi-ary encoding protocol exploiting the nonseparability of orbital angular momentum (OAM) and polarization for a hybrid vector beam. Such an encoding can be realized in high-dimensional state space by transforming OAM of the vector beam under the assistance of polarization, which is called "high-dimensional" encoding. It is shown that N-ary encoding using N dimensional non-separable basis can be obtained by manipulating N/2 different OAM modes, which is equivalent to encoding log2N bits of information. It is also shown that the decoding of vector beams can be realized with very low cross talk. Compared with the encoding protocol transforming OAM modes of scalar beams, our encoding scheme, based on classical nonseparability of vector beams, can encode much more information. This is of great benefit to the optical communication. PMID- 27410667 TI - Monolithic semiconductor chips as a source for broadband wavelength-multiplexed polarization entangled photons. AB - Generating entangled photons from a monolithic chip is a major milestone towards real-life applications of optical quantum information processing including quantum key distribution and quantum computing. Ultrabroadband entangled photons are of particular interest to various applications such as quantum metrology and multi-party entanglement distribution. In this work, we demonstrate the direct generation of broadband wavelength-multiplexed polarization entangled photons from a semiconductor chip for the first time. Without the use of any off-chip compensation or interferometry, entangled photons with a signal-idler separation as large as 95 nm in the telecom band were observed. The highest concurrence of 0.98+/-0.01 achieved in this work is also the highest, to the best of our knowledge, comparing to all previously demonstrated semiconductor waveguide sources. This work paves the way for fully integrated, ultrabroadband sources of polarization entangled photons. PMID- 27410668 TI - Spin Helicity in Chiral Lanthanide Chains. AB - We report here the determination of the helical spin structure of three Ln-based chiral chains of the formula [Ln(Hnic)(nic)2(NO3)]n (Hnic = nicotinic acid; Ln = Tb, Dy, and Er) by means of cantilever torque magnetometry. While the Dy and Er derivatives are strongly axial (easy-axis and easy-plane anisotropy, respectively), the Tb derivative is characterized by a remarkable rhombicity. In agreement with these findings, alternating-current susceptibility reveals slow magnetic relaxation only in the Dy derivative. Dilution of DyIII ions in the diamagnetic Y-based analogue shows that the weak ferromagnetic intrachain interactions do not contribute significantly to the energy barrier for the reversal of magnetization, which is better described as a single-ion process. Single crystals of the two enantiomers of the Dy derivative have also been investigated using hard X-ray synchrotron radiation at the L-edge of the metal revealing optical activity although with negligible involvement of the 4f electrons of the DyIII ion. PMID- 27410669 TI - On-Demand Dissolution of a Dendritic Hydrogel-based Dressing for Second-Degree Burn Wounds through Thiol-Thioester Exchange Reaction. AB - An adhesive yet easily removable burn wound dressing represents a breakthrough in second-degree burn wound care. Current second-degree burn wound dressings absorb wound exudate, reduce bacterial infections, and maintain a moist environment for healing, but are surgically or mechanically debrided from the wound, causing additional trauma to the newly formed tissues. We have developed an on-demand dissolvable dendritic thioester hydrogel burn dressing for second-degree burn care. The hydrogel is composed of a lysine-based dendron and a PEG-based crosslinker, which are synthesized in high yields. The hydrogel burn dressing covers the wound and acts as a barrier to bacterial infection in an in vivo second-degree burn wound model. A unique feature of the hydrogel is its capability to be dissolved on-demand, via a thiol-thioester exchange reaction, allowing for a facile burn dressing removal. PMID- 27410670 TI - Observation of Binding and Rotation of Methane and Hydrogen within a Functional Metal-Organic Framework. AB - The key requirement for a portable store of natural gas is to maximize the amount of gas within the smallest possible space. The packing of methane (CH4) in a given storage medium at the highest possible density is, therefore, a highly desirable but challenging target. We report a microporous hydroxyl-decorated material, MFM-300(In) (MFM = Manchester Framework Material, replacing the NOTT designation), which displays a high volumetric uptake of 202 v/v at 298 K and 35 bar for CH4 and 488 v/v at 77 K and 20 bar for H2. Direct observation and quantification of the location, binding, and rotational modes of adsorbed CH4 and H2 molecules within this host have been achieved, using neutron diffraction and inelastic neutron scattering experiments, coupled with density functional theory (DFT) modeling. These complementary techniques reveal a very efficient packing of H2 and CH4 molecules within MFM-300(In), reminiscent of the condensed gas in pure component crystalline solids. We also report here, for the first time, the experimental observation of a direct binding interaction between adsorbed CH4 molecules and the hydroxyl groups within the pore of a material. This is different from the arrangement found in CH4/water clathrates, the CH4 store of nature. PMID- 27410671 TI - Coping with domestic violence against children and adolescents from the perspective of primary care nurses. AB - OBJECTIVE: To analyse the actions reported by primary care nurses in the fight against domestic violence against children and adolescents. METHODS: Qualitative research conducted at five family health centres in the state of Sao Paulo, Brazil. Data were collected in the second half of 2013 through semi-structured. RESULTS: Two thematic cores emerged: "Public policies identified by the nurses" and "Nurses' actions regarding violence permeated by fear and conflicts". The nurses were familiar with public policies, but they were unable to put them into practice; they were unprepared to identify and cope with the violence; they did not participate in training courses; they were afraid to report the detected cases of violence. CONCLUSION: The main limitations to the practical work of nurses are work burden, lack of security, and the dynamics of work that is not articulated with the protection network, which causes the underreporting of cases of domestic violence. PMID- 27410672 TI - Courses offered by the Minas Health Channel: perception of primary care workers. AB - OBJECTIVE: To analyse how primary healthcare workers perceive the impact of the Health Channel Mines courses in their work process. METHOD: This is a descriptive exploratory qualitative study conducted with 38 professionals working in primary health care units of three municipalities in the state of Minas Gerais, Brazil. Data were collected in 2014 by means of semi-structured interviews and subjected to thematic content analysis. RESULTS: Data analysis revealed the following three categories: interest in training and its contribution to professional practice; factors that alter professional practices; and proposals for improvement. CONCLUSION: The study data demonstrated that the Mines Health Channel courses cannot single-handedly change professional practices. Continued and refresher education resources that enable the exchange and articulation of knowledge between the various specialities are needed to transform professional practices. PMID- 27410673 TI - Clinical and socio-demographic characteristics of patients at a rehabilitation center for chemical dependency. AB - OBJECTIVE: Identify the socio-demographic and clinical characteristics of a sample of chemically dependent people undergoing treatment at a daytime ambulatory care center specialized in treating chemical dependency in Lima, Peru, and describe their dropout rates. METHOD: Quantitative, descriptive, and exploratory study based on secondary data. The instrument used was the individual notification record from the information system for the treatment demand. RESULTS: The demand was composed mostly of young, single men who were unemployed or underemployed. The most common diagnosis was dependency on cocaine-based drugs and the age of the onset of use was between 15 and 19 years. The dropout rate was 85%, and 48% remained in treatment for only one day. CONCLUSION: The results highlight important factors to be considered in the evaluation of public policies on prevention, treatment, and supply control. We recommend more inclusive and participatory public policies. PMID- 27410674 TI - Hyperbaric oxygen therapy for wound care. AB - OBJECTIVE: To describe the most common types of wounds indicated for hyperbaric oxygen therapy and the results. METHOD: Cross-sectional study at a Hyperbaric Centre in the city of Salvador, Bahia, Brazil. The medical records of 200 patients treated with hyperbaric oxygen were reviewed from January to November 2013. The variables of the persons, clinical, indications, number of sessions and wound care were analysed by means of descriptive statistics and the chi-square test of association incorporating Yates's correction with a level of 5%. RESULTS: The wounds that were most frequently indicated for hyperbaric oxygen therapy were venous ulcers, traumatic injury and diabetic foot. Patients with chronic wounds had fewer sessions (61.1%) and their wounds healed or were reduced (62.0%) compared to those with acute wounds. CONCLUSION: Hyperbaric oxygen therapy is an effective treatment for patients with chronic wounds. PMID- 27410676 TI - Use of a Barbed Knotless Suture for Laparoscopic Ablation of the Nephrosplenic Space in 8 Horses. AB - OBJECTIVE: To evaluate use of a knotless suture for laparoscopic closure of the equine nephrosplenic space. STUDY DESIGN: Experimental in vivo study. ANIMALS: Normal horses without previous history of abdominal surgery (n=8). METHODS: The nephrosplenic space was closed under laparoscopic visualization using a unidirectional, barbed 0 metric absorbable suture (copolymer of glycolic acid and trimethylene carbonate). Intracorporeal suturing of the nephrosplenic space was performed in a cranial-to-caudal direction in a simple continuous fashion. Repeat evaluation was performed laparoscopically in 2 horses and by necropsy in 6 horses. The length of closure was measured and nature of the healed tissue was evaluate grossly. RESULTS: Total surgery time was 65-167 minutes (mean +/- SD, 89.6 +/- 22.6). Suturing time was 30-65 minutes (40.4 +/- 16.3). Second laparoscopy in 2 horses was performed at days 198 and 227. Necropsy was performed at day 69-229 postoperatively (132.7 +/- 63.0) in 6 horses. The closure measured 12-14 cm in length (13 +/- 1) and consisted of mature fibrous tissue bridging the splenic capsule and the nephrosplenic ligament. No residual suture material was identified grossly in any horses. The procedure was easily performed; extracorporeal suture management to hold it taut was unnecessary since the barbs had excellent purchase in the apposed tissues, and intracorporeal knot tying was not required. CONCLUSION: The barbed knotless suture appears to be a valid alternative to facilitate laparoscopic closure of the nephrosplenic space in normal horses; however, further work is necessary to investigate its suitability in clinically affected horses. PMID- 27410675 TI - Applicability of nursing outcomes in patients with heart failure and fluid volume excessive. AB - OBJECTIVE: The purpose of this study was to test the clinical applicability of the Nursing Outcomes Classification in patients with decompensated heart failure and the nursing diagnosis of fluid volume excess. METHODS: This is a longitudinal study conducted in two stages at a university hospital, in 2013. During the first stage the consensus of experts was used to select the nursing outcomes and the indicators related to diagnosing fluid volume excess. The longitudinal study was conducted in the second stage to clinically evaluate the patients using the instrument containing the results and indicators produced in the consensus. RESULTS: A total of 17 patients were assessed. The nursing outcomes were measured during the clinical evaluation by analysing their indicators. The scores increased in six of the results, in comparison with the average results of the first and last assessment. The Nursing Outcomes Classification during medical practice revealed a clinical improvement among the patient who were admitted following decompensated heart failure. CONCLUSION: The Nursing Outcomes Classification managed to detect changes in the clinical status of patients. PMID- 27410677 TI - A Small Molecule That Represses Translation of G-Quadruplex-Containing mRNA. AB - The G-quadruplexes form highly stable nucleic acid structures, which are implicated in various biological processes in both DNA and RNA. Although DNA G quadruplexes have been studied in great detail, biological roles of RNA G quadruplexes have received less attention. Here, a screening of a chemical library permitted identification of a small-molecule tool that binds selectively to RNA G-quadruplex structures. The polyaromatic molecule, RGB-1, stabilizes RNA G-quadruplex, but not DNA versions or other RNA structures. RGB-1 intensified the G-quadruplex-mediated inhibition of RNA translation in mammalian cells, decreased expression of the NRAS proto-oncogene in breast cancer cells, and permitted identification of a novel sequence that forms G-quadruplex in NRAS mRNA. RGB-1 may serve as a unique tool for understanding cellular roles of RNA G-quadruplex structures. PMID- 27410678 TI - Fragility, fluidity, and resilience: caregiving configurations three decades into AIDS. AB - HIV and AIDS have impacted on social relations in many ways, eroding personal networks, contributing to household poverty, and rupturing intimate relations. With the continuing transmission of HIV particularly in resource-poor settings, families and others must find new ways to care for those who are living with HIV, for those who are ill and need increased levels of personal and medical care, and for orphaned children. These needs occur concurrently with changes in family structure, as a direct result of HIV-related deaths but also due to industrialization, urbanization, and labor migration. In this special issue, the contributing authors draw on ethnographies from South Africa, Swaziland, Lesotho, Zambia, and - by way of contrast - China, to illustrate how people find new ways of constituting families, or of providing alternatives to families, in order to provide care and support to people infected with and afflicted by HIV. PMID- 27410679 TI - Benzoic-Imine-Based Physiological-pH-Responsive Materials for Biomedical Applications. AB - The benzoic imine is a dynamic covalent bond, which is stable around neutral pH value (ca. 7.4), but starts to hydrolyze at the extracellular pH value of solid tumors (ca. 6.5) and rapidly disintegrates at endosome and lysosome pH values (ca. 4.5-6.5). This characteristic is promising for the construction of physiological-pH-responsive materials, such as polymeric micelles, nanoparticles, and hydrogels for pharmaceutical and tissue-engineering applications. This Focus Review summarizes recent progress in the design and synthesis of pH-sensitive materials that contain the benzoic imine bond with biomedical objectives. PMID- 27410680 TI - Exploring cognitive reserve in multiple sclerosis: New findings from a cross sectional study. AB - INTRODUCTION: The cognitive reserve (CR) hypothesis attempts to explain the discrepancy between brain damage and clinical manifestations in neurodegenerative diseases. Recently the concept of CR was applied to the multiple sclerosis (MS) model. Our aim is to investigate the impact of demographic and clinical variables on cognitive outcome in MS patients. METHOD: A total of 72 MS patients were assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), and high field magnetic resonance examination. We performed a multivariate linear regression analysis, including each cognitive test scores as dependent variables and CRI together with age, normalized brain volume (NBV), normalized cortical volume (NCV), expanded disability severity scale (EDSS) score, and disease duration as independent variables. Moreover, we assessed whether one of the CRI subscores (CRI-Education, CRI-WorkingActivity, CRI-LeisureTime) predicted cognitive performance more than the other. Finally, to assess the CR hypothesis in our sample, we conducted the same analyses including the interaction term CRI * NCV. RESULTS: From the multiple regression analysis, it emerged that the CRI total score influenced sustained attention, concentration, information processing speed, and verbal learning. Among the three CRI subscores, CRI-Education and CRI-WorkingActivity had the most influence. Age and EDSS score were the other significant predictors. We did not find evidence for a moderation effect of CR on negative influence of atrophy on cognitive status. CONCLUSIONS: This study focused on the contribution of CR to predict neuropsychological outcome in MS. We used a new standardized questionnaire to provide a global index including three main source of CR: education, working activity, and leisure time activities. Our preliminary findings suggest that the CR is an important predictor of better performance on cognitive tests in MS patients. However, at this stage of the study, we are unable to confirm the CR hypothesis. PMID- 27410682 TI - Dynamics of the Water Circulations in the Southern South China Sea and Its Seasonal Transports. AB - A three-dimensional Regional Ocean Modeling System is used to study the seasonal water circulations and transports of the Southern South China Sea. The simulated seasonal water circulations and estimated transports show consistency with observations, e.g., satellite altimeter data set and re-analysis data of the Simple Ocean Data Assimilation. It is found that the seasonal water circulations are mainly driven by the monsoonal wind stress and influenced by the water outflow/inflow and associated currents of the entire South China Sea. The intrusion of the strong current along the East Coast of Peninsular Malaysia and the eddies at different depths in all seasons are due to the conservation of the potential vorticity as the depth increases. Results show that the water circulation patterns in the northern part of the East Coast of Peninsular Malaysia are generally dominated by the geostrophic currents while those in the southern areas are due solely to the wind stress because of negligible Coriolis force there. This study clearly shows that individual surface freshwater flux (evaporation minus precipitation) controls the sea salinity balance in the Southern South China Sea thermohaline circulations. Analysis of climatological data from a high resolution Regional Ocean Modeling System reveals that the complex bathymetry is important not only for water exchange through the Southern South China Sea but also in regulating various transports across the main passages in the Southern South China Sea, namely the Sunda Shelf and the Strait of Malacca. Apart from the above, in comparision with the dynamics of the Sunda Shelf, the Strait of Malacca reflects an equally significant role in the annual transports into the Andaman Sea. PMID- 27410681 TI - Lack of Correlation between Aberrant p16, RAR-beta2, TIMP3, ERCC1, and BRCA1 Protein Expression and Promoter Methylation in Squamous Cell Carcinoma Accompanying Candida albicans-Induced Inflammation. AB - Hyperplastic candidiasis is characterized by thickening of the mucosal epithelia with Candida albicans infection with occasional progression to squamous cell carcinoma (SCC). C. albicans is a critical factor in tumor development; however, the oncogenic mechanism is unclear. We have previously produced an animal model for hyperplastic candidiasis in the rat forestomach. In the present study, we investigate whether impaired DNA methylation and associated protein expression of tumor suppressor and DNA repair genes are involved in the SCC carcinogenesis process using this hyperplastic candidiasis model. Promoter methylation and protein expression were analyzed by methylation specific PCR and immunohistochemical staining, respectively, of 5 areas in the forestomachs of alloxan-induced diabetic rats with hyperplastic candidiasis: normal squamous epithelia, squamous hyperplasia, squamous hyperplasia adjacent to SCC, squamous hyperplasia transitioning to SCC, and SCC. We observed nuclear p16 overexpression despite increases in p16 gene promoter methylation during the carcinogenic process. TIMP3 and RAR-beta2 promoter methylation progressed until the precancerous stage but disappeared upon malignant transformation. In comparison, TIMP3 protein expression was suppressed during carcinogenesis and RAR-beta2 expression was attenuated in the cytoplasm but enhanced in nuclei. ERCC1 and BRCA1 promoters were not methylated at any stage; however, their protein expression disappeared beginning at hyperplasia and nuclear protein re-expression in SCC was observed only for ERCC1. These results suggest that aberrant p16, RAR beta2, TIMP3, ERCC1, and BRCA1 expression might occur that is inconsistent with the respective gene promoter methylation status, and that this overexpression might serve to promote the inflammatory carcinogenesis caused by C. albicans infection. PMID- 27410683 TI - An Unusual New Theropod with a Didactyl Manus from the Upper Cretaceous of Patagonia, Argentina. AB - BACKGROUND: Late Cretaceous terrestrial strata of the Neuquen Basin, northern Patagonia, Argentina have yielded a rich fauna of dinosaurs and other vertebrates. The diversity of saurischian dinosaurs is particularly high, especially in the late Cenomanian-early Turonian Huincul Formation, which has yielded specimens of rebacchisaurid and titanosaurian sauropods, and abelisaurid and carcharodontosaurid theropods. Continued sampling is adding to the known vertebrate diversity of this unit. METHODOLOGY/ PRINCIPAL FINDINGS: A new, partially articulated mid-sized theropod was found in rocks from the Huincul Formation. It exhibits a unique combination of traits that distinguish it from other known theropods justifying erection of a new taxon, Gualicho shinyae gen. et sp. nov. Gualicho possesses a didactyl manus with the third digit reduced to a metacarpal splint reminiscent of tyrannosaurids, but both phylogenetic and multivariate analyses indicate that didactyly is convergent in these groups. Derived characters of the scapula, femur, and fibula supports the new theropod as the sister taxon of the nearly coeval African theropod Deltadromeus and as a neovenatorid carcharodontosaurian. A number of these features are independently present in ceratosaurs, and Gualicho exhibits an unusual mosaic of ceratosaurian and tetanuran synapomorphies distributed throughout the skeleton. CONCLUSIONS/ SIGNIFICANCE: Gualicho shinyae gen. et sp. nov. increases the known theropod diversity of the Huincul Formation and also represents the first likely neovenatorid from this unit. It is the most basal tetatanuran to exhibit common patterns of digit III reduction that evolved independently in a number of other tetanuran lineages. A close relationship with Deltadromaeus from the Kem Kem beds of Niger adds to the already considerable biogeographic similarity between the Huincul Formation and coeval rock units in North Africa. PMID- 27410684 TI - Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip. AB - In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of 18F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [18F]SFB using a batch reactor and microreactor and developed a new continuous flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [18F]SFB. In the synthesis of [18F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 +/- 2% (n = 5). In addition, it was shown that the quality of [18F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [18F]SFB. PMID- 27410685 TI - Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis. AB - Induction of mucosal healing (MH) is an important treatment goal in inflammatory bowel disease (IBD). Although the molecular mechanisms underlying MH in IBD is not fully explored, local fibrosis would contribute to interfere mucosal repair. Carbohydrate sulfotransferase 15 (CHST15), which catalyzes sulfation of chondroitin sulfate to produce rare E-disaccharide units, is a novel mediator to create local fibrosis. Here we have used siRNA-based approach of silencing CHST15 in dextran sulfate sodium (DSS) induced colitis in mice, human colon fibroblasts and cancer cell lines. In a DSS-induced acute colitis model, CHST15 siRNA reduced CHST15 mRNA in the colon, serum IL-6, disease activity index (DAI) and accumulation of F4/80+ macrophages and ER-TR7+ fibroblasts, while increased Ki 67+ epithelial cells. In DSS-induced chronic colitis models, CHST15 siRNA reduced CHST15 mRNA in the colon, DAI, alpha-smooth muscle actin+ fibroblasts and collagen deposition, while enhanced MH as evidenced by reduced histological and endoscopic scores. We also found that endoscopic submucosal injection achieved effective pancolonic delivery of CHST15 siRNA in mice. In human CCD-18 Co cells, CHST15 siRNA inhibited the expression of CHST15 mRNA and selectively reduced E units, a specific product biosynthesized by CHST15, in the culture supernatant. CHST15 siRNA significantly suppressed vimentin in both TGF-beta-stimulated CCD18 Co cells and HCT116 cells while up-regulated BMP7 and E-cadherin in HCT116 cells. The present study demonstrated that blockade CHST15 represses colonic fibrosis and enhances MH partly though reversing EMT pathway, illustrating a novel therapeutic opportunity to refractory and fibrotic lesions in IBD. PMID- 27410686 TI - Germline genetic variation in JAK2 as a prognostic marker in castration-resistant prostate cancer. AB - OBJECTIVES: To evaluate the prognostic significance of germline variation in candidate genes in patients with castration-resistant prostate cancer (CRPC). METHODS: Germline DNA was extracted from peripheral blood mononuclear cells of patients with CRPC enrolled in a clinically annotated registry. Fourteen candidate genes implicated in either initiation or progression of prostate cancer were tagged using single nucleotide polymorphisms (SNPs) from HapMap with a minor allele frequency of >5%. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. Principal component analysis was used for gene levels tests of significance. For SNP-level results the per allele hazard ratios (HRs) and 95% confidence intervals (CIs) under the additive allele model were estimated using Cox regression, adjusted for age at CRPC and Gleason score (GS). RESULTS: A total of 240 patients with CRPC were genotyped (14 genes; 84 SNPs). The median (range) age of the cohort was 69 (43-93) years. The GS distribution was 55% with GS >=8, 32% with GS = 7 and 13% with GS <7 or unknown. The median (interquartile range) time from castration resistance to death for the cohort was 2.67 (1.6-4.07) years (144 deaths). At the gene level, a single gene, JAK2 was associated with OS (P < 0.01), and 11 of 18 JAK2 SNPs were individually associated with OS after adjustment for age and GS. A multivariate model consisting of age, GS, rs2149556 (HR 0.67; 95% CI 0.38-1.18) and rs4372063 (HR 2.17; 95% CI 1.25-3.76) was constructed to predict survival in patients with CRPC (concordance of 0.69, P < 3.2 * 10-9 ). CONCLUSIONS: Germline variation in the JAK2 gene was associated with survival in patients with CRPC and warrants further validation as a potential prognostic biomarker. PMID- 27410687 TI - Voluntary Medical Male Circumcision for HIV Prevention in Swaziland: Modeling the Impact of Age Targeting. AB - BACKGROUND: Voluntary medical male circumcision (VMMC) for HIV prevention has been a priority for Swaziland since 2009. Initially focusing on men ages 15-49, the Ministry of Health reduced the minimum age for VMMC from 15 to 10 years in 2012, given the existing demand among 10- to 15-year-olds. To understand the implications of focusing VMMC service delivery on specific age groups, the MOH undertook a modeling exercise to inform policy and implementation in 2013-2014. METHODS AND FINDINGS: The impact and cost of circumcising specific age groups were assessed using the Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0), a simple compartmental model. We used age-specific HIV incidence from the Swaziland HIV Incidence Measurement Survey (SHIMS). Population, mortality, births, and HIV prevalence were imported from a national Spectrum/Goals model recently updated in consultation with country stakeholders. Baseline male circumcision prevalence was derived from the most recent Swaziland Demographic and Health Survey. The lowest numbers of VMMCs per HIV infection averted are achieved when males ages 15-19, 20-24, 25-29, and 30-34 are circumcised, although the uncertainty bounds for the estimates overlap. Circumcising males ages 25-29 and 20-24 provides the most immediate reduction in HIV incidence. Circumcising males ages 15-19, 20-24, and 25-29 provides the greatest magnitude incidence reduction within 15 years. The lowest cost per HIV infection averted is achieved by circumcising males ages 15-34: $870 U.S. dollars (USD). CONCLUSIONS: The potential impact, cost, and cost-effectiveness of VMMC scale-up in Swaziland are not uniform. They vary by the age group of males circumcised. Based on the results of this modeling exercise, the Ministry of Health's Swaziland Male Circumcision Strategic and Operational Plan 2014-2018 adopted an implementation strategy that calls for circumcision to be scaled up to 50% coverage for neonates, 80% among males ages 10-29, and 55% among males ages 30-34. PMID- 27410689 TI - Afri-Can Forum 2 : Johannesburg, South Africa. 16-18 February 2015. PMID- 27410688 TI - Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data. AB - BACKGROUND: BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC), and it is associated with high-risk prognostic factors. However, the significance of the BRAF mRNA level in PTC remains unknown. We evaluated the significance of BRAF mRNA expression level by analyzing PTC data from The Cancer Genome Atlas (TCGA) database. METHODS: Data from 499 patients were downloaded from the TCGA database. After excluding other PTC variants, we selected 353 cases of classic PTC, including 193 cases with BRAFV600E and 160 cases with the wild type BRAF. mRNA abundances were measured using RNA-Seq with the Expectation Maximization algorithm. RESULTS: The mean BRAF mRNA level was significantly higher in BRAFV600E patients than in patients with wild-type BRAF (197.6 vs. 179.3, p = 0.031). In wild-type BRAF patients, the mean BRAF mRNA level was higher in cases with a tumor > 2 cm than those with a tumor <= 2.0 cm (189.4 vs. 163.8, p = 0.046), and was also higher in cases with lymph node metastasis than in those without lymph node metastasis (188.5 vs. 157.9, p = 0.040). Within BRAFV600E patients, higher BRAF mRNA expression was associated with extrathyroidal extension (186.4 vs. 216.4, p = 0.001) and higher T stage (188.1 vs. 210.2, p = 0.016). CONCLUSIONS: A higher BRAF mRNA expression level was associated with tumor aggressiveness in classic PTC regardless of BRAF mutational status. Evaluation of BRAF mRNA level may be helpful in prognostic risk stratification of PTC. PMID- 27410690 TI - Novel Treatment Using Cimetidine for Erythropoietic Protoporphyria in Children. AB - Importance: Erythropoietic protoporphyria (EPP) is a rare hereditary disease of heme biosynthesis that manifests as severe photosensitivity and hepatotoxicity. There have been no effective treatments to date. Cimetidine has been shown to inhibit heme biosynthesis and results in symptomatic improvement in patients with acute intermittent porphyria (AIP) and porphyria cutanea tarda (PCT). There is only 1 report in the literature describing the use of cimetidine in the effective treatment of an adult patient with EPP. Objective: To describe the successful use of cimetidine in pediatric patients with EPP. Design, Setting, and Participants: Retrospective medical record review carried out in a pediatric dermatology practice at an academic institution of patients diagnosed with EPP who were younger than 18 years and treated with systemic cimetidine in the past 3 years. Interventions: Systemic cimetidine. Main Outcomes and Measures: Resolution of skin photodamage was evaluated on clinical examination. Subjective measures including tolerability to sun exposure, ability to participate in outdoor activities, and objective evaluation including serum erythrocyte protoporphyrin levels and liver function tests following treatment were assessed. Results: All 3 cases reported a rapid reduction in photosensitivity within weeks following initiation of systemic therapy. Their skin photodamage were also improved or resolved completely on subsequent examination. Laboratory study results also revealed reduction in serum erythrocyte protoporphyrin levels and improved liver function. None of the patients have reported any adverse effects of the systemic treatment after more than 2 years of treatment. Conclusions and Relevance: Children with EPP currently have limited therapeutic options and experience substantial disease impact on their quality of life. This is the first case series demonstrating that cimetidine, a readily available oral medication, can be a promising treatment for children with EPP. PMID- 27410692 TI - Coming in sportsmedicine. PMID- 27410693 TI - Letters. PMID- 27410691 TI - Impact of Chaos Functions on Modern Swarm Optimizers. AB - Exploration and exploitation are two essential components for any optimization algorithm. Much exploration leads to oscillation and premature convergence while too much exploitation slows down the optimization algorithm and the optimizer may be stuck in local minima. Therefore, balancing the rates of exploration and exploitation at the optimization lifetime is a challenge. This study evaluates the impact of using chaos-based control of exploration/exploitation rates against using the systematic native control. Three modern algorithms were used in the study namely grey wolf optimizer (GWO), antlion optimizer (ALO) and moth-flame optimizer (MFO) in the domain of machine learning for feature selection. Results on a set of standard machine learning data using a set of assessment indicators prove advance in optimization algorithm performance when using variational repeated periods of declined exploration rates over using systematically decreased exploration rates. PMID- 27410694 TI - Brief reports. PMID- 27410696 TI - Moderate Drinking Ok. PMID- 27410697 TI - Mouth Guards Eat Up Injury Rate. PMID- 27410698 TI - Characteristics of Child Distance Runners. AB - In brief: Little is known about the motivating factors, training regimens, and injuries in child distance runners, Forty participants (ages 8 to 15) in a 10-km road race completed a questionnaire indicating previous training and race experience. Twenty percent of the runners ran six to seven days per week, and 40% logged more than 15 miles a week. Eighteen percent had experienced an overuse injury. Enjoyment and parental encouragement were common motivating factors. Medical care providers can help promote aerobic exercise and minimize the risks, but the increasing involvement of children in running may have outstripped the knowledge of physicians who practice sports medicine. PMID- 27410699 TI - The Medical Aspects of Boxing. AB - In brief: Whether boxing should be banned is one of the most controversial topics in sports today. In this round table discussion the participating physicians present their views from a medical standpoint. The safety of boxers is influenced by teaching methods, rules and their enforcement, equipment, prebout and postbout physical examinations, requalifying injured boxers, common boxing injuries and their long-term effects, and preventing injury. PMID- 27410700 TI - The Preventive Use of the Anderson Knee Stabler in Football. AB - In brief: The Anderson knee stabler restricts the valgus stress to the knee joint, which should decrease the number and severity of collateral ligament injuries and reduce the number of meniscal injuries. The authors reviewed medical records of football players at the University of Southern California (USC) and recorded the number and type of knee surgeries from 1980 to 1984, noting which players wore braces and which did not. Results showed that the Anderson knee stabler is beneficial in preventing collateral ligament and meniscus injuries to the knee. There have been no grade-3 injuries to the collateral ligaments caused by direct contact to the brace. The authors recommend that all USC linebackers and interior linemen wear the Anderson knee stabler during practices and games but say that further longitudinal data are needed. PMID- 27410701 TI - How I Manage Fractured Metacarpals in Athletes. AB - In brief: The six most common types of metacarpal fractures are (1) intra articular fractures of the metacarpophalangeal joint; (2) compacted fractures through the metacarpal neck-the so-called boxer's or punch fracture; (3) transverse or short oblique fractures of the shaft; (4) spiral fractures of the shaft; (5) proximal fractures and fracture-dislocations of the fifth metacarpal; and (6) thumb metacarpal fractures. Conservative treatment is preferable for most injuries of the hand, but surgical repair is indicated in a few patients. Some sports regulate whether a cast can be worn during competition, but many athletes with these fractures can return to early participation with a splinting device that offers optimal protection to both the injured player and the Opponent. PMID- 27410702 TI - Attitudes Toward Drug Abuse and Screening for an Intercollegiate Athletic Program. AB - In brief: A number of universities have started screening intercollegiate athletes for drugs. A 26-item questionnaire administered to students, athletes, former athletes, parents of athletes, high school athletes, alumni, faculty members, and coaches at the University of Alabama revealed significant differences between student and nonstudent perceptions of drug abuse as a problem. There was widespread support for the screening program among nonathletes but significantly less support among the athletes. PMID- 27410703 TI - Youth Accidents With Horses. AB - In brief: In a two-year study of the estimated 13,428,000 hours of horse activities by 18,408 US Pony Clubs (USPC) members aged 6 to 21 in scheduled supervised programs, there were 64 accidents resulting in 88 injuries in 16 areas of the body. The head/face was the area most often injured (27.27%), and bruise/abrasion was the most common type of injury (28.26%). Cross-country riding was the most dangerous event (42.31%). Unexpected actions of the horse caused many accidents-25% occurred when the horse bucked and threw the rider, 23.08% when the horse refused a jump, and 17.31% when the horse fell or slipped. There were only two accidents to the most skilled riders, but riders with five or more years of experience had the highest percentage of accidents. PMID- 27410704 TI - Preventing Injury in Competitive Canoeists. AB - In brief: Competitive canoeists and kayakers often suffer from injuries to the wrist, forearm, shoulder, and lower back. The author discusses the types of injuries that occur and suggests ways to prevent and treat them. Modifying stroke technique and strengthening and stretching specific problem areas can help prevent injury. Treatment modalities include rest or modified training; nonsteroidal anti-inflammatory agents; ice for acute injury; and heat, ultrasound, and massage before training, followed by ice for subacute or chronic injuries. The physician and the athlete can fashion a training program for the injury prone paddler that prevents injury without diluting the quality of overall training. PMID- 27410705 TI - On the Rebound: A Fitness Love Affair. AB - Rebounders-the minitrampolines used for jogging or exercise routines-have sparked mixed feelings. Some exercise enthusiasts love them, many researchers don't. It is the story of a fitness fad trying to achieve respectability. PMID- 27410706 TI - Knee Braces: Questions Raised About Performance. AB - Do knee braces live up to their promotional billings? Maybe not, according to a report released by the Sports Medicine Committee of the American Academy of Orthopedic Surgeons. PMID- 27410707 TI - Do DRGs Hold the Future of Cardiac Rehabilitation? AB - While hospitals look to cut corners in an effort to be more cost efficient, cardiac rehabilitation programs seek to prove that they help get patients out of the hospital faster. What's behind these efforts? Diagnosis related groups, of course. PMID- 27410708 TI - The Role of Exercise in Managing Diabetes. AB - Approximately 11 million Americans have diabetes mellitus, which with its complications is the third-leading cause of death by disease in the United States. Exercise is particularly important in managing diabetes. PMID- 27410710 TI - Scanning sports. PMID- 27410709 TI - Calcium and Healthy Bones. PMID- 27410712 TI - What About Anaerobic Exercise? PMID- 27410714 TI - 16p11.2 deletion and duplication: Characterizing neurologic phenotypes in a large clinically ascertained cohort. AB - Chromosome 16p11.2 deletions and duplications are among the most frequent genetic etiologies of autism spectrum disorder (ASD) and other neurodevelopmental disorders, but detailed descriptions of their neurologic phenotypes have not yet been completed. We utilized standardized examination and history methods to characterize a neurologic phenotype in 136 carriers of 16p11.2 deletion and 110 carriers of 16p11.2 duplication-the largest cohort to date of uniformly and comprehensively characterized individuals with the same 16p copy number variants (CNVs). The 16p11.2 deletion neurologic phenotype is characterized by highly prevalent speech articulation abnormalities, limb and trunk hypotonia with hyporeflexia, abnormalities of agility, sacral dimples, seizures/epilepsy, large head size/macrocephaly, and Chiari I/cerebellar tonsillar ectopia. Speech articulation abnormalities, hypotonia, abnormal agility, sacral dimples, and seizures/epilepsy are also seen in duplication carriers, along with more prominent hyperreflexia; less, though still prevalent, hyporeflexia; highly prevalent action tremor; small head size/microcephaly; and cerebral white matter/corpus callosum abnormalities and ventricular enlargement. The neurologic phenotypes of these reciprocal 16p11.2 CNVs include both shared and distinct features. Reciprocal phenotypic characteristics of predominant hypo- versus hyperreflexia and macro- versus microcephaly may reflect opposite neurobiological abnormalities with converging effects causing the functional impairments shared between 16p11.2 deletion and duplication carriers (i.e., abnormal motor agility and articulation). While the phenotypes exhibit overlap with other genetically caused neurodevelopmental disorders, clinicians should be aware of the more striking features-such as the speech and motor impairments, growth abnormalities, tremor, and sacral dimples-when evaluating individuals with developmental delay, intellectual disability, ASD, and/or language disorders. (c) 2016 Wiley Periodicals, Inc. PMID- 27410715 TI - Gender differences in non-standard mapping tasks: A kinematic study using pantomimed reach-to-grasp actions. AB - Comparison between real and pantomimed actions is used in neuroscience to dissociate stimulus-driven (real) as compared to internally driven (pantomimed) visuomotor transformations, with the goal of testing models of vision (Milner & Goodale, 1995) and diagnosing neuropsychological deficits (apraxia syndrome). Real actions refer to an overt movement directed toward a visible target whereas pantomimed actions refer to an overt movement directed either toward an object that is no longer available. Although similar, real and pantomimed actions differ in their kinematic parameters and in their neural substrates. Pantomimed-reach-to grasp-actions show reduced reaching velocities, higher wrist movements, and reduced grip apertures. In addition, seminal neuropsychological studies and recent neuroimaging findings confirmed that real and pantomimed actions are underpinned by separate brain networks. Although previous literature suggests differences in the praxis system between males and females, no research to date has investigated whether or not gender differences exist in the context of real versus pantomimed reach-to-grasp actions. We asked ten male and ten female participants to perform real and pantomimed reach-to-grasp actions toward objects of different sizes, either with or without visual feedback. During pantomimed actions participants were required to pick up an imaginary object slightly offset relative to the location of the real one (which was in turn the target of the real reach-to-grasp actions). Results demonstrate a significant difference between the kinematic parameters recorded in male and female participants performing pantomimed, but not real reach-to-grasp tasks, depending on the availability of visual feedback. With no feedback both males and females showed smaller grip aperture, slower movement velocity and lower reach height. Crucially, these same differences were abolished when visual feedback was available in male, but not in female participants. Our results suggest that male and female participants should be evaluated separately in the clinical environment and in future research in the field. PMID- 27410716 TI - Synthesis of Tetrahydroisoquinoline Alkaloids and Related Compounds through the Alkylation of Anodically Prepared alpha-Amino Nitriles. AB - alpha-Amino nitrile 2a was conveniently prepared in two individual steps from chiral hexafluorophosphate salt isoquinolinium (-)-8b including anodic cyanation as an efficient means to activate the sp(3) C1-H bond of the THIQ nucleus. The lithiation of 2a was carried out in THF at -80 degrees C in the presence of LDA to produce a stable alpha-amino carbanion which was condensed on a large variety of alkyl halides. The resulting quaternary alpha-amino nitriles were subjected to a stereoselective reductive decyanation in ethanol in the presence of NaBH4 as the hydride donor to yield N-Boc-1-alkyl-THIQs (+)-10a-g in up to 97:3 er's after removal of the chiral auxiliary group. Examination of the ORTEP view of THIQ (+) 1f revealed that the newly created stereogenic center had an absolute S configuration. Likewise, (-)-xylopinine was synthesized in four workup steps in an overall 63% yield from alpha-amino nitrile (+)-2b. In this process, crystallization of an enantioenriched mixture (90:10) of (-)-norlaudanosine with 1 equiv of (-)-N-acetyl-l-leucine afforded the leucinate salt (+)-13 (99:1 dr). Similarly, (+)-salsolidine was displaced from its (-)-DBTA salt (-)-12 in 99:1 er, which was determined by proton and carbon NMR spectroscopy in the presence of thiophosphinic acid (+)-14 as the chiral solvating agent. PMID- 27410717 TI - A Flexible Terpyridine Derivative Interacts Specifically with G-Quadruplexes. AB - G-quadruplexes formed by nucleic acids are implicated in pathologies ranging from cancers to neurodegenerative diseases. We evaluated interactions of 29 bi- and terpyridine derivatives with G-quadruplexes and duplexes. FRET-melting, circular dichroism, and (1) H NMR spectroscopy showed that one terpyridine derivative interacted very selectively with G-quadruplexes. This G-quadruplex ligand inhibited helicase activity and should influence G-quadruplex-related biological processes. PMID- 27410718 TI - Safety of hyperbaric oxygen therapy for management of central airway stenosis after lung transplant. AB - BACKGROUND: Central airway stenosis (CAS) is common after lung transplantation and causes significant post-transplant morbidity. It is often preceded by extensive airway necrosis, related to airway ischemia. Hyperbaric oxygen therapy (HBOT) is useful for ischemic grafts and may reduce the development of CAS. METHODS: The purpose of this study was to determine whether HBOT could be safely administered to lung transplant patients with extensive necrotic airway plaques. Secondarily, we assessed any effects of HBOT on the incidence and severity of CAS. Patients with extensive necrotic airway plaques within 1-2 months after lung transplantation were treated with HBOT along with standard care. These patients were compared with a contemporaneous reference group with similar plaques who did not receive HBOT. RESULTS: Ten patients received HBOT for 18.5 (interquartile range, IQR 11-20) sessions, starting at 40.5 (IQR 34-54) days after transplantation. HBOT was well tolerated. Incidence of CAS was similar between HBOT-treated patients and reference patients (70% vs 87%, respectively; P=.34), but fewer stents were required in HBOT patients (10% vs 56%, respectively; P=.03). CONCLUSIONS: This pilot study is the first to demonstrate HBOT safety in patients who develop necrotic airway plaques after lung transplantation. HBOT may reduce the need for airway stent placement in patients with CAS. PMID- 27410719 TI - [Passive immunization in dogs and cats]. AB - Antibodies play an important role in the defense against infectious diseases. Passive immunization provides immediate protection through transfer of exogenous antibodies to a recipient. It is mainly used for prophylaxis in dogs and cats that failed to receive maternal antibodies through the colostrum or when there is an acute risk to acquire infectious diseases. Only a small number of placebo controlled studies have been published regarding the therapeutic use of passive immunization in small animals. While positive effects were reported in cats with acute virus infections of the upper respiratory tract and in dogs with distemper, no statistically significant influence could be demonstrated in the treatment of canine parvovirosis. Prospective, double-blinded, and placebo-controlled studies using adequate numbers of patients are warranted for a definitive statement regarding the therapeutic and prophylactic use of passive immunization in dogs and cats. PMID- 27410720 TI - Zirconocene-Mediated Carbonylative Coupling of Grignard Reagents. AB - Organozirconocenes are versatile synthetic intermediates that can undergo carbonylation to yield acyl anion equivalents. Zirconocene hydrochloride ([Cp2 ZrHCl]) is often the reagent of choice for accessing these intermediates but generates organozirconocenes only from alkenes and alkynes. This requirement eliminates a broad range of substrates. For example, organozirconocenes in which the zirconium center is bonded to an aromatic ring, a benzylic group, or an alkyl group that possesses a tertiary or quaternary carbon atom alpha to the carbon zirconium bond can not be formed in this way. To provide more generalized access to acyl zirconium reagents, we explored the transmetalation of Grignard reagents with zirconocene dichloride under a CO atmosphere. This protocol generates acyl zirconium(IV) complexes that are inaccessible with the Schwartz reagent, including those derived from secondary and tertiary alkyl and aryl Grignard reagents. PMID- 27410721 TI - A review of treatment options for bile duct stones. AB - INTRODUCTION: Approximately 10-15% of bile duct stones cannot be treated using conventional stone removal techniques. For difficult common bile duct stones (CBDS), various endoscopic techniques have been developed. This review covers technical tips and endoscopic treatments including Endoscopic retrograde cholangiopancreatography (ERCP), particularly under Endoscopic ultrasound (EUS) guidance. Areas covered: Literatures about endoscopic treatment for bile duct stone were searched in Pub Med. As novel methods, EUS-guided approaches have also been reported, although long-term results and prospective evaluation are not yet sufficient. Large stones may need fragmentation prior to removal, to prevent stone impaction. To perform fragmentation, mechanical lithotripsy, extracorporeal shock wave lithotripsy or laser lithotripsy techniques are available. Expert commentary: Despite the fact that most bile duct stones can be treated using endoscopic techniques, endoscopists should remind to be able to select the temporary biliary stenting or percutaneous transhepatic cholangiodrainage as an option. PMID- 27410722 TI - The Transition from Thin Basement Membranes to Typical Alport Syndrome Morphology in Children. AB - Some children with thin basement membranes (TBM) turn out to have Alport syndrome (AS). In our population of 58 children initially diagnosed with TBM, three were eventually diagnosed with AS. As a group, these three were first biopsied at a younger age, and had gross rather than microscopic hematuria. Only one had lamellations initially. Seven others had some degree of basement membrane lamellations at initial biopsy, but none of these have developed other features of AS. We concluded that at least 5% of children initially demonstrating TBM go on to manifest the classical electron-microscopic findings of AS during childhood. Episodes of gross hematuria with TBM can be a significant clue of AS. Genetic and/or immunofluorescent studies for type IV collagen, and continued long term follow-up should be done in all children with TBM. PMID- 27410723 TI - In vitro and in vivo genotoxicity assessment of selected pharmaceuticals in relation to Escherichia coli and Cyprinus carpio. AB - Genotoxicity studies (using SOS chromotest and comet assay) of Escherichia coli and carp (Cyprinus carpio) were performed for three pharmaceutically active compounds, ciprofloxacin, 17alpha-ethinylestradiol and 5-fluorouracil, used in the treatment of humans. The values of genotoxicity induction coefficient (I) in the SOS chromotest clearly showed genotoxicity for ciprofloxacin, both in the presence and in the absence of S9 fraction; 17alpha-ethinylestradiol demonstrated slight genotoxicity at the highest tested concentration; and 5-fluorouracil did not induce genotoxic effects in Escherichia coli mutants. Statistical analysis of the results of the comet assay revealed significant differences in cell populations derived from carp placed in a solution of 5-fluorouracil in comparison with the negative control. Statistical analysis also showed a significant increase of "% DNA in tail" of comets in cell populations incubated in solutions of 17alpha-ethinylestradiol at concentrations of 10000, 2000 and 400 ug/L and in solutions of 5-fluorouracil with S9 fraction at concentrations of 50,000 and 2,000 MUg/L in comparison with the negative controls. PMID- 27410724 TI - ERRATUM. AB - [This corrects the article DOI: 10.1016/S0377-1237(07)80082-7.]. PMID- 27410725 TI - Linguistic validation of stigmatisation degree, self-esteem and knowledge questionnaire among asthma patients using Rasch analysis. AB - BACKGROUND AND OBJECTIVE: The stigmatisation degree, self-esteem and knowledge either directly or indirectly influence the control and self-management of asthma. To date, there is no valid and reliable instrument that can assess these key issues collectively. The main aim of this study was to test the reliability and validity of the newly devised and translated "Stigmatisation Degree, Self Esteem and Knowledge Questionnaire" among adult asthma patients using the Rasch measurement model. METHODOLOGY: This cross-sectional study recruited thirty adult asthma patients from two respiratory specialist clinics in Selangor, Malaysia. The newly devised self-administered questionnaire was adapted from relevant publications and translated into the Malay language using international standard translation guidelines. Content and face validation was done. The data were extracted and analysed for real item reliability and construct validation using the Rasch model. RESULTS AND CONCLUSION: The translated "Stigmatisation Degree, Self-Esteem and Knowledge Questionnaire" showed high real item reliability values of 0.90, 0.86 and 0.89 for stigmatisation degree, self-esteem, and knowledge of asthma, respectively. Furthermore, all values of point measure correlation (PTMEA Corr) analysis were within the acceptable specified range of the Rasch model. Infit/outfit mean square values and Z standard (ZSTD) values of each item verified the construct validity and suggested retaining all the items in the questionnaire. The reliability analyses and output tables of item measures for construct validation proved the translated Malaysian version of "Stigmatisation Degree, Self-Esteem and Knowledge Questionnaire" as a valid and highly reliable questionnaire. PMID- 27410726 TI - GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. PMID- 27410727 TI - Complexity Revealed: A Hierarchy of Clustered Membrane Proteins. PMID- 27410728 TI - Is TMC1 the Hair Cell Mechanotransducer Channel? AB - Transmembrane channel-like protein isoform-1 (TMC1) has emerged over the past five years as a prime contender for the mechano-electrical transducer (MET) channel in hair cells of the inner ear. TMC1 is thought to have a six transmembrane domain structure reminiscent of some other ion-channel subunits, and is targeted to the tips of the stereocilia in the sensory hair bundle, where the MET channel is located. Moreover, there are TMC1 mutations linked to human deafness causing loss of conventional MET currents, hair cell degeneration, and deafness in mice. Finally, mutations of Tmc1 can alter the conductance and Ca(2+) selectivity of the MET channels. For several reasons though, it is unclear that TMC1 is indeed the MET channel pore: 1) in other animals or tissues, mutations of TMC family members do not directly affect cellular mechanosensitivity; 2) there are residual manifestations of mechanosensitivity in hair cells of mouse Tmc1:Tmc2 double knockouts; 3) there is so far no evidence that expression of mammalian Tmc1 generates a mechanically sensitive ion channel in the plasma membrane when expressed in heterologous cells; and 4) there are other proteins, such as TMIE and LHFPL5, which behave similarly to TMC1, their mutation also leading to loss of MET current and deafness. This review will present these disparate lines of evidence and describes recent work that addresses the role of TMC1. PMID- 27410729 TI - Using Evolution to Guide Protein Engineering: The Devil IS in the Details. AB - For decades, protein engineers have endeavored to reengineer existing proteins for novel applications. Overall, protein folds and gross functions can be readily transferred from one protein to another by transplanting large blocks of sequence (i.e., domain recombination). However, predictably fine-tuning function (e.g., by adjusting ligand affinity, specificity, catalysis, and/or allosteric regulation) remains a challenge. One approach has been to use the sequences of protein families to identify amino acid positions that change during the evolution of functional variation. The rationale is that these nonconserved positions could be mutated to predictably fine-tune function. Evolutionary approaches to protein design have had some success, but the engineered proteins seldom replicate the functional performances of natural proteins. This Biophysical Perspective reviews several complexities that have been revealed by evolutionary and experimental studies of protein function. These include 1) challenges in defining computational and biological thresholds that define important amino acids; 2) the co-occurrence of many different patterns of amino acid changes in evolutionary data; 3) difficulties in mapping the patterns of amino acid changes to discrete functional parameters; 4) the nonconventional mutational outcomes that occur for a particular group of functionally important, nonconserved positions; 5) epistasis (nonadditivity) among multiple mutations; and 6) the fact that a large fraction of a protein's amino acids contribute to its overall function. To overcome these challenges, new goals are identified for future studies. PMID- 27410730 TI - Improved Determination of Subnuclear Position Enabled by Three-Dimensional Membrane Reconstruction. AB - Many aspects of chromatin biology are influenced by the nuclear compartment in which a locus resides, from transcriptional regulation to DNA repair. Further, the dynamic and variable localization of a particular locus across cell populations and over time makes analysis of a large number of cells critical. As a consequence, robust and automatable methods to measure the position of individual loci within the nuclear volume in populations of cells are necessary to support quantitative analysis of nuclear position. Here, we describe a three dimensional membrane reconstruction approach that uses fluorescently tagged nuclear envelope or endoplasmic reticulum membrane marker proteins to precisely map the nuclear volume. This approach is robust to a variety of nuclear shapes, providing greater biological accuracy than alternative methods that enforce nuclear circularity, while also describing nuclear position in all three dimensions. By combining this method with established approaches to reconstruct the position of diffraction-limited chromatin markers-in this case, lac Operator arrays bound by lacI-GFP-the distribution of loci positions within the nuclear volume with respect to the nuclear periphery can be quantitatively obtained. This stand-alone image analysis pipeline should be of broad practical utility for individuals interested in various aspects of chromatin biology, while also providing, to our knowledge, a new conceptual framework for investigators who study organelle shape. PMID- 27410731 TI - Protein Composition Determines the Effect of Crowding on the Properties of Disordered Proteins. AB - Unlike dilute experimental conditions under which biological molecules are typically characterized, the cell interior is crowded by macromolecules, which affects both the thermodynamics and kinetics of in vivo processes. Although the excluded-volume effects of macromolecular crowding are expected to cause compaction of unfolded and disordered proteins, the extent of this effect is uncertain. We use a coarse-grained model to represent proteins with varying sequence content and directly observe changes in chain dimensions in the presence of purely repulsive spherical crowders. We find that the extent of crowding induced compaction is dependent not only on crowder size and concentration, but also on the properties of the protein itself. In fact, we observe a nonmonotonic trend between the dimensions of the polypeptide chain in bulk and the degree of compaction: the most extended chains experience up to 24% compaction, the most compact chains show virtually no change, and intermediate chains compress by up to 40% in size at a 40% crowder volume fraction. Free-volume theory combined with an impenetrable ellipsoidal representation of the chains predicts the crowding effects only for collapsed protein chains. An additional scaling factor, which can be easily computed from protein-crowder potential of mean force, corrects for the penetrability of extended chains and is sufficient to capture the observed nonmonotonic trend in compaction. PMID- 27410732 TI - Characterization of Zebrafish Cardiac and Slow Skeletal Troponin C Paralogs by MD Simulation and ITC. AB - Zebrafish, as a model for teleost fish, have two paralogous troponin C (TnC) genes that are expressed in the heart differentially in response to temperature acclimation. Upon Ca(2+) binding, TnC changes conformation and exposes a hydrophobic patch that interacts with troponin I and initiates cardiac muscle contraction. Teleost-specific TnC paralogs have not yet been functionally characterized. In this study we have modeled the structures of the paralogs using molecular dynamics simulations at 18 degrees C and 28 degrees C and calculated the different Ca(2+)-binding properties between the teleost cardiac (cTnC or TnC1a) and slow-skeletal (ssTnC or TnC1b) paralogs through potential-of-mean force calculations. These values are compared with thermodynamic binding properties obtained through isothermal titration calorimetry (ITC). The modeled structures of each of the paralogs are similar at each temperature, with the exception of helix C, which flanks the Ca(2+) binding site; this region is also home to paralog-specific sequence substitutions that we predict have an influence on protein function. The short timescale of the potential-of-mean-force calculation precludes the inclusion of the conformational change on the DeltaG of Ca(2+) interaction, whereas the ITC analysis includes the Ca(2+) binding and conformational change of the TnC molecule. ITC analysis has revealed that ssTnC has higher Ca(2+) affinity than cTnC for Ca(2+) overall, whereas each of the paralogs has increased affinity at 28 degrees C compared to 18 degrees C. Microsecond-timescale simulations have calculated that the cTnC paralog transitions from the closed to the open state more readily than the ssTnC paralog, an unfavorable transition that would decrease the ITC-derived Ca(2+) affinity while simultaneously increasing the Ca(2+) sensitivity of the myofilament. We propose that the preferential expression of cTnC at lower temperatures increases myofilament Ca(2+) sensitivity by this mechanism, despite the lower Ca(2+) affinity that we have measured by ITC. PMID- 27410733 TI - Nanomechanics of Type I Collagen. AB - Type I collagen is the predominant collagen in mature tendons and ligaments, where it gives them their load-bearing mechanical properties. Fibrils of type I collagen are formed by the packing of polypeptide triple helices. Higher-order structures like fibril bundles and fibers are assembled from fibrils in the presence of other collagenous molecules and noncollagenous molecules. Curiously, however, experiments show that fibrils/fibril bundles are less resistant to axial stress compared to their constituent triple helices-the Young's moduli of fibrils/fibril bundles are an order-of-magnitude smaller than the Young's moduli of triple helices. Given the sensitivity of the Young's moduli of triple helices to solvation environment, a plausible explanation is that the packing of triple helices into fibrils perhaps reduces the Young's modulus of an individual triple helix, which results in fibrils having smaller Young's moduli. We find, however, from molecular dynamics and accelerated conformational sampling simulations that the Young's modulus of the buried core of the fibril is of the same order as that of a triple helix in aqueous phase. These simulations, therefore, suggest that the lower Young's moduli of fibrils/fibril bundles cannot be attributed to the specific packing of triple helices in the fibril core. It is not the fibril core that yields initially to axial stress. Rather, it must be the portion of the fibril exposed to the solvent and/or the fibril-fibril interface that bears the initial strain. Overall, this work provides estimates of Young's moduli and persistence lengths at two levels of collagen's structural assembly, which are necessary to quantitatively investigate the response of various biological factors on collagen mechanics, including congenital mutations, posttranslational modifications and ligand binding, and also engineer new collagen-based materials. PMID- 27410734 TI - Pregnancy-Induced Dynamical and Structural Changes of Reproductive Tract Collagen. AB - The tissues and organs of the female reproductive tract and pelvic floor undergo significant remodeling and alterations to allow for fetal growth and birth. In this work, we report on a study of the alterations of murine reproductive tract collagen resulting from pregnancy and parturition by spectrophotometry, histology, and (13)C, (2)H nuclear magnetic resonance (NMR). Four different cohorts of rats were investigated that included virgin, multiparous, two- and fourteen-day postpartum primiparous rats. (13)C CPMAS NMR revealed small chemical shift differences across the cohorts. The measured H-C internuclear correlation times indicated differences in dynamics of some motifs. However, the dynamics of the major amino acids, e.g., Gly, remained unaltered with respect to parity. (2)H NMR relaxation measurements revealed an additional water reservoir in the postpartum and multiparous cohorts pointing to redistribution of water due to pregnancy and/or parturition. Spectrophotometric measurements indicated that the collagen content in virgin rats was highest. Histological analysis of the upper vaginal wall indicated a signature of collagen fiber dissociation with smooth muscle and a change in the density of collagen fibers in multiparous rats. PMID- 27410735 TI - Structure Change from beta-Strand and Turn to alpha-Helix in Histone H2A-H2B Induced by DNA Damage Response. AB - Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of alpha-helix structure and a decrease of beta-strand and turn structures in histone H2A-H2B extracted from x irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new alpha-helix structures at 310 K. We propose the structural transition from beta-strand and turn structures to an alpha-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response. PMID- 27410736 TI - The Molecular Switching Mechanism at the Conserved D(E)RY Motif in Class-A GPCRs. AB - The disruption of ionic and H-bond interactions between the cytosolic ends of transmembrane helices TM3 and TM6 of class-A (rhodopsin-like) G protein-coupled receptors (GPCRs) is a hallmark for their activation by chemical or physical stimuli. In the bovine photoreceptor rhodopsin, this is accompanied by proton uptake at Glu(134) in the class-conserved D(E)RY motif. Studies on TM3 model peptides proposed a crucial role of the lipid bilayer in linking protonation to stabilization of an active state-like conformation. However, the molecular details of this linkage could not be resolved and have been addressed in this study by molecular dynamics (MD) simulations on TM3 model peptides in a bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We show that protonation of the conserved glutamic acid alters the peptide insertion depth in the membrane, its side-chain rotamer preferences, and stabilizes the C-terminal helical structure. These factors contribute to the rise of the side-chain pKa (> 6) and to reduced polarity around the TM3 C terminus as confirmed by fluorescence spectroscopy. Helix stabilization requires the protonated carboxyl group; unexpectedly, this stabilization could not be evoked with an amide in MD simulations. Additionally, time-resolved Fourier transform infrared (FTIR) spectroscopy of TM3 model peptides revealed a different kinetics for lipid ester carbonyl hydration, suggesting that the carboxyl is linked to more extended H bond clusters than an amide. Remarkably, this was seen as well in DOPC reconstituted Glu(134)- and Gln(134)-containing bovine opsin mutants and demonstrates that the D(E)RY motif is a hydrated microdomain. The function of the D(E)RY motif as a proton switch is suggested to be based on the reorganization of the H-bond network at the membrane interface. PMID- 27410737 TI - The Water Permeability and Pore Entrance Structure of Aquaporin-4 Depend on Lipid Bilayer Thickness. AB - Aquaporin-4 (AQP4), the primary water channel in glial cells of the mammalian brain, plays a critical role in water transport in the central nervous system. Previous experiments have shown that the water permeability of AQP4 depends on the cholesterol content in the lipid bilayer, but it was not clear whether changes in permeability were due to direct cholesterol-AQP4 interactions or to indirect effects caused by cholesterol-induced changes in bilayer elasticity or bilayer thickness. To determine the effects resulting only from bilayer thickness, here we use a combination of experiments and simulations to analyze AQP4 in cholesterol-free phospholipid bilayers with similar elastic properties but different hydrocarbon core thicknesses previously determined by x-ray diffraction. The channel (unit) water permeabilities of AQP4 measured by osmotic gradient experiments were 3.5 +/- 0.2 * 10(-13) cm(3)/s (mean +/- SE), 3.0 +/- 0.3 * 10(-13) cm(3)/s, 2.5 +/- 0.2 * 10(-13) cm(3)/s, and 0.9 +/- 0.1 * 10(-13) cm(3)/s in bilayers containing (C22:1)(C22:1)PC, (C20:1)(C20:1)PC, (C16:0)(C18:1)PC, and (C13:0)(C13:0)PC, respectively. Channel permeabilities obtained by molecular dynamics (MD) simulations were 3.3 +/- 0.1 * 10(-13) cm(3)/s and 2.5 +/- 0.1 * 10(-13) cm(3)/s in (C22:1)(C22:1)PC and (C14:0)(C14:0)PC bilayers, respectively. Both the osmotic-gradient and MD simulation results indicated that AQP4 channel permeability decreased with decreasing bilayer hydrocarbon thickness. The MD simulations also suggested structural modifications in AQP4 in response to changes in bilayer thickness. Although the simulations showed no appreciable changes to the radius of the pore located in the hydrocarbon region of the bilayers, the simulations indicated that there were changes in both pore length and alpha-helix organization near the cytoplasmic vestibule of the channel. These structural changes, caused by mismatch between the hydrophobic length of AQP4 and the bilayer hydrocarbon thickness, could explain the observed differences in water permeability with changes in bilayer thickness. PMID- 27410739 TI - Regulation of K-Ras4B Membrane Binding by Calmodulin. AB - K-Ras4B is a membrane-bound small GTPase with a prominent role in cancer development. It contains a polybasic farnesylated C-terminus that is required for the correct localization and clustering of K-Ras4B in distinct membrane domains. PDEdelta and the Ca(2+)-binding protein calmodulin (CaM) are known to function as potential binding partners for farnesylated Ras proteins. However, they differ in the number of interaction sites with K-Ras4B, leading to different modes of interaction, and thus affect the subcellular distribution of K-Ras4B in different ways. Although it is clear that Ca(2+)-bound CaM can play a role in the dynamic spatial cycle of K-Ras4B in the cell, the exact molecular mechanism is only partially understood. In this biophysical study, we investigated the effect of Ca(2+)/CaM on the interaction of GDP- and GTP-loaded K-Ras4B with heterogeneous model biomembranes by using a combination of different spectroscopic and imaging techniques. The results show that Ca(2+)/CaM is able to extract K-Ras4B from negatively charged membranes in a nucleotide-independent manner. Moreover, the data demonstrate that the complex of Ca(2+)/CaM and K-Ras4B is stable in the presence of anionic membranes and shows no membrane binding. Finally, the influence of Ca(2+)/CaM on the interaction of K-Ras4B with membranes is compared with that of PDEdelta, which was investigated in a previous study. Although both CaM and PDEdelta exhibit a hydrophobic binding pocket for farnesyl, they have different effects on membrane binding of K-Ras4B and hence should be capable of regulating K-Ras4B plasma membrane localization in the cell. PMID- 27410738 TI - MHC I Expression Regulates Co-clustering and Mobility of Interleukin-2 and -15 Receptors in T Cells. AB - MHC glycoproteins form supramolecular clusters with interleukin-2 and -15 receptors in lipid rafts of T cells. The role of highly expressed MHC I in maintaining these clusters is unknown. We knocked down MHC I in FT7.10 human T cells, and studied protein clustering at two hierarchic levels: molecular aggregations and mobility by Forster resonance energy transfer and fluorescence correlation spectroscopy; and segregation into larger domains or superclusters by superresolution stimulated emission depletion microscopy. Fluorescence correlation spectroscopy-based molecular brightness analysis revealed that the studied molecules diffused as tight aggregates of several proteins of a kind. Knockdown reduced the number of MHC I containing molecular aggregates and their average MHC I content, and decreased the heteroassociation of MHC I with IL 2Ralpha/IL-15Ralpha. The mobility of not only MHC I but also that of IL 2Ralpha/IL-15Ralpha increased, corroborating the general size decrease of tight aggregates. A multifaceted analysis of stimulated emission depletion images revealed that the diameter of MHC I superclusters diminished from 400-600 to 200 300 nm, whereas those of IL-2Ralpha/IL-15Ralpha hardly changed. MHC I and IL 2Ralpha/IL-15Ralpha colocalized with GM1 ganglioside-rich lipid rafts, but MHC I clusters retracted to smaller subsets of GM1- and IL-2Ralpha/IL-15Ralpha-rich areas upon knockdown. Our results prove that changes in expression level may significantly alter the organization and mobility of interacting membrane proteins. PMID- 27410740 TI - Disentangling Viral Membrane Fusion from Receptor Binding Using Synthetic DNA Lipid Conjugates. AB - Enveloped viruses must bind to a receptor on the host membrane to initiate infection. Membrane fusion is subsequently initiated by a conformational change in the viral fusion protein, triggered by receptor binding, an environmental change, or both. Here, we present a strategy to disentangle the two processes of receptor binding and fusion using synthetic DNA-lipid conjugates to bind enveloped viruses to target membranes in the absence of receptor. This permits direct testing of whether receptor engagement affects the fusion mechanism as well as a comparison of fusion behavior across viruses with different receptor binding specificities. We demonstrate this approach by binding X-31 influenza virus to target vesicles and measuring the rates of individual pH-triggered lipid mixing events using fluorescence microscopy. Influenza lipid mixing kinetics are found to be independent of receptor binding, supporting the common yet previously unproven assumption that receptor binding does not produce any clustering or spatial rearrangement of viral hemagglutinin, which affects the rate-limiting step of pH-triggered fusion. This DNA-lipid tethering strategy should also allow the study of viruses where challenging receptor reconstitution has previously prevented single-virus fusion experiments. PMID- 27410741 TI - Mode of Action of Antimicrobial Peptides on E. coli Spheroplasts. AB - We investigated the phenomena of antimicrobial peptides (AMPs) directly attacking the cytoplasmic membranes of Escherichia coli spheroplasts. We developed a procedure for fluorescence recovery after photobleaching to examine dye leakage through bacterial membranes as AMPs in solution bound to the membranes. We found that the AMP binding did not increase the apparent membrane area of a spheroplast, contrary to the response of a lipid-bilayer vesicle, which always showed a membrane area expansion by AMP binding. The permeability through the bacterial membrane increased in a sigmoidal fashion as the AMP binding increased in time, exhibiting a cooperative behavior of AMPs. The analysis of fluorescence recovery after photobleaching showed that the fluxes of dye molecules into and out of the cell were consistent with diffusion of molecules through a number of pores that increased with binding of AMPs and then saturated to a steady level. We discovered a new, to our knowledge, experimental parameter called the flux rate that characterizes the AMP-induced permeability of dye molecules through bacterial membranes. The phenomena observed in bacterial membranes are consistent with the pore-forming activities of AMPs previously observed in lipid bilayers. The experimental value of the flux rate per pore is much smaller than a theoretical value that assumes no friction for the dye molecule's permeation through the pore. We believe that experimental studies of the flux rate will be useful for further analysis of AMPs' permeabilization mechanisms. PMID- 27410743 TI - On the Equivalence of FCS and FRAP: Simultaneous Lipid Membrane Measurements. AB - Fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP) are widely used methods to determine diffusion coefficients. However, they often do not yield the same results. With the advent of camera-based imaging FCS, which measures the diffusion coefficient in each pixel of an image, and proper bleaching corrections, it is now possible to measure the diffusion coefficient by FRAP and FCS in the exact same images. We thus performed simultaneous FCS and FRAP measurements on supported lipid bilayers and live cell membranes to test how far the two methods differ in their results and whether the methodological differences, in particular the high bleach intensity in FRAP, the bleach corrections, and the fitting procedures in the two methods explain observed differences. Overall, we find that the FRAP bleach intensity does not measurably influence the diffusion in the samples, but that bleach correction and fitting introduce large uncertainties in FRAP. We confirm our results by simulations. PMID- 27410742 TI - The Role of Cholesterol in Driving IAPP-Membrane Interactions. AB - Our knowledge of the molecular events underlying type 2 diabetes mellitus-a protein conformational disease characterized by the aggregation of islet amyloid polypeptide (IAPP) in pancreatic beta cells-is limited. However, amyloid-mediated membrane damage is known to play a key role in IAPP cytotoxicity, and therefore the effects of lipid composition on modulating IAPP-membrane interactions have been the focus of intense research. In particular, membrane cholesterol content varies with aging and consequently with adverse environmental factors such as diet and lifestyle, but its role in the development of the disease is controversial. In this study, we employ a combination of experimental techniques and in silico molecular simulations to shed light on the role of cholesterol in IAPP aggregation and the related membrane disruption. We show that if anionic POPC/POPS vesicles are used as model membranes, cholesterol has a negligible effect on the kinetics of IAPP fibril growth on the surface of the bilayer. In addition, cholesterol inhibits membrane damage by amyloid-induced poration on membranes, but enhances leakage through fiber growth on the membrane surface. Conversely, if 1:2 DOPC/DPPC raft-like model membranes are used, cholesterol accelerates fiber growth. Next, it enhances pore formation and suppresses fiber growth on the membrane surface, leading to leakage. Our results highlight a twofold effect of cholesterol on the amyloidogenicity of IAPP and help explain its debated role in type 2 diabetes mellitus. PMID- 27410745 TI - Macromolecular Crowding Modulates Actomyosin Kinetics. AB - Actomyosin kinetics is usually studied in dilute solutions, which do not reflect conditions in the cytoplasm. In cells, myosin and actin work in a dense macromolecular environment. High concentrations of macromolecules dramatically reduce the amount of free space available for all solutes, which results in an effective increase of the solutes' chemical potential and protein stabilization. Moreover, in a crowded solution, the chemical potential depends on the size of the solute, with larger molecules experiencing a larger excluded volume than smaller ones. Therefore, since myosin interacts with two ligands of different sizes (actin and ATP), macromolecular crowding can modulate the kinetics of individual steps of the actomyosin ATPase cycle. To emulate the effect of crowding in cells, we studied actomyosin cycle reactions in the presence of a high-molecular-weight polymer, Ficoll70. We observed an increase in the maximum velocity of the actomyosin ATPase cycle, and our transient-kinetics experiments showed that virtually all individual steps of the actomyosin cycle were affected by the addition of Ficoll70. The observed effects of macromolecular crowding on the myosin-ligand interaction cannot be explained by the increase of a solute's chemical potential. A time-resolved Forster resonance energy transfer experiment confirmed that the myosin head assumes a more compact conformation in the presence of Ficoll70 than in a dilute solution. We conclude that the crowding induced myosin conformational change plays a major role in the changed kinetics of actomyosin ATPase. PMID- 27410744 TI - Forces from the Portal Govern the Late-Stage DNA Transport in a Viral DNA Packaging Nanomotor. AB - In the Phi29 bacteriophage, the DNA packaging nanomotor packs its double-stranded DNA genome into the virus capsid. At the late stage of DNA packaging, the negatively charged genome is increasingly compacted at a higher density in the capsid with a higher internal pressure. During the process, two Donnan effects, osmotic pressure and Donnan equilibrium potentials, are significantly amplified, which, in turn, affect the channel activity of the portal protein, GP10, embedded in the semipermeable capsid shell. In the research, planar lipid bilayer experiments were used to study the channel activities of the viral protein. The Donnan effect on the conformational changes of the viral protein was discovered, indicating GP10 may not be a static channel at the late stage of DNA packaging. Due to the conformational changes, GP10 may generate electrostatic forces that govern the DNA transport. For the section of the genome DNA that remains outside of the connector channel, a strong repulsive force from the viral protein would be generated against the DNA entry; however, for the section of the genome DNA within the channel, the portal protein would become a Brownian motor, which adopts the flash Brownian ratchet mechanism to pump the DNA against the increasingly built-up internal pressure (up to 20 atm) in the capsid. Therefore, the DNA transport in the nanoscale viral channel at the late stage of DNA packaging could be a consequence of Brownian movement of the genomic DNA, which would be rectified and harnessed by the forces from the interior wall of the viral channel under the influence of the Donnan effect. PMID- 27410746 TI - Efficient Multiscale Models of Polymer Assembly. AB - Protein polymerization and bundling play a central role in cell physiology. Predictive modeling of these processes remains an open challenge, especially when the proteins involved become large and their concentrations high. We present an effective kinetics model of filament formation, bundling, and depolymerization after GTP hydrolysis, which involves a relatively small number of species and reactions, and remains robust over a wide range of concentrations and timescales. We apply this general model to study assembly of FtsZ protein, a basic element in the division process of prokaryotic cells such as Escherichia coli, Bacillus subtilis, or Caulobacter crescentus. This analysis demonstrates that our model outperforms its counterparts in terms of both accuracy and computational efficiency. Because our model comprises only 17 ordinary differential equations, its computational cost is orders-of-magnitude smaller than the current alternatives consisting of up to 1000 ordinary differential equations. It also provides, to our knowledge, a new insight into the characteristics and functioning of FtsZ proteins at high concentrations. The simplicity and versatility of our model render it a powerful computational tool, which can be used either as a standalone descriptor of other biopolymers' assembly or as a component in more complete kinetic models. PMID- 27410747 TI - Nanonet Force Microscopy for Measuring Cell Forces. AB - The influence of physical forces exerted by or felt by cells on cell shape, migration, and cytoskeleton arrangement is now widely acknowledged and hypothesized to occur due to modulation of cellular inside-out forces in response to changes in the external fibrous environment (outside-in). Our previous work using the non-electrospinning Spinneret-based Tunable Engineered Parameters' suspended fibers has revealed that cells are able to sense and respond to changes in fiber curvature and structural stiffness as evidenced by alterations to focal adhesion cluster lengths. Here, we present the development and application of a suspended nanonet platform for measuring C2C12 mouse myoblast forces attached to fibers of three diameters (250, 400, and 800 nm) representing a wide range of structural stiffness (3-50 nN/MUm). The nanonet force microscopy platform measures cell adhesion forces in response to symmetric and asymmetric external perturbation in single and cyclic modes. We find that contractility-based, inside out forces are evenly distributed at the edges of the cell, and that forces are dependent on fiber structural stiffness. Additionally, external perturbation in symmetric and asymmetric modes biases cell-fiber failure location without affecting the outside-in forces of cell-fiber adhesion. We then extend the platform to measure forces of (1) cell-cell junctions, (2) single cells undergoing cyclic perturbation in the presence of drugs, and (3) cancerous single cells transitioning from a blebbing to a pseudopodial morphology. PMID- 27410748 TI - Shear-Induced Nitric Oxide Production by Endothelial Cells. AB - We present a biochemical model of the wall shear stress-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell. The model includes three key mechanotransducers: mechanosensing ion channels, integrins, and G protein-coupled receptors. The reaction cascade consists of two interconnected parts. The first is rapid activation of calcium, which results in formation of calcium-calmodulin complexes, followed by recruitment of eNOS from caveolae. The second is phosphorylation of eNOS by protein kinases PKC and AKT. The model also includes a negative feedback loop due to inhibition of calcium influx into the cell by cyclic guanosine monophosphate (cGMP). In this feedback, increased nitric oxide (NO) levels cause an increase in cGMP levels, so that cGMP inhibition of calcium influx can limit NO production. The model was used to predict the dynamics of NO production by an endothelial cell subjected to a step increase of wall shear stress from zero to a finite physiologically relevant value. Among several experimentally observed features, the model predicts a highly nonlinear, biphasic transient behavior of eNOS activation and NO production: a rapid initial activation due to the very rapid influx of calcium into the cytosol (occurring within 1-5 min) is followed by a sustained period of activation due to protein kinases. PMID- 27410749 TI - Clathrin Assembly Regulated by Adaptor Proteins in Coarse-Grained Models. AB - The assembly of clathrin triskelia into polyhedral cages during endocytosis is regulated by adaptor proteins (APs). We explore how APs achieve this by developing coarse-grained models for clathrin and AP2, employing a Monte Carlo click interaction, to simulate their collective aggregation behavior. The phase diagrams indicate that a crucial role is played by the mechanical properties of the disordered linker segment of AP. We also present a statistical-mechanical theory for the assembly behavior of clathrin, yielding good agreement with our simulations and experimental data from the literature. Adaptor proteins are found to regulate the formation of clathrin coats under certain conditions, but can also suppress the formation of cages. PMID- 27410750 TI - Pericellular Brush and Mechanics of Guinea Pig Fibroblast Cells Studied with AFM. AB - The atomic force microscopy (AFM) indentation method combined with the brush model can be used to separate the mechanical response of the cell body from deformation of the pericellular layer surrounding biological cells. Although self consistency of the brush model to derive the elastic modulus of the cell body has been demonstrated, the model ability to characterize the pericellular layer has not been explicitly verified. Here we demonstrate it by using enzymatic removal of hyaluronic content of the pericellular brush for guinea pig fibroblast cells. The effect of this removal is clearly seen in the AFM force-separation curves associated with the pericellular brush layer. We further extend the brush model for brushes larger than the height of the AFM probe, which seems to be the case for fibroblast cells. In addition, we demonstrate that an extension of the brush model (i.e., double-brush model) is capable of detecting the hierarchical structure of the pericellular brush, which, for example, may consist of the pericellular coat and the membrane corrugation (microridges and microvilli). It allows us to quantitatively segregate the large soft polysaccharide pericellular coat from a relatively rigid and dense membrane corrugation layer. This was verified by comparison of the parameters of the membrane corrugation layer derived from the force curves collected on untreated cells (when this corrugation membrane part is hidden inside the pericellular brush layer) and on treated cells after the enzymatic removal of the pericellular coat part (when the corrugations are exposed to the AFM probe). We conclude that the brush model is capable of not only measuring the mechanics of the cell body but also the parameters of the pericellular brush layer, including quantitative characterization of the pericellular layer structure. PMID- 27410751 TI - Anomalous Fluctuations in the Orientation and Velocity of Swarming Bacteria. AB - Simultaneous acquisition of phase-contrast light microscopy and fluorescently labeled bacteria, moving within a dense swarm, reveals the intricate interactions between cells and the collective flow around them. By comparing wild-type and immotile cells embedded in a dense wild-type swarm, the effect of the active thrust generated by the flagella can be singled out. It is shown that while the distribution of angles among cell velocity, cell orientation, and the local flow around it is Gaussian-like for immotile bacteria, wild-type cells exhibit anomalous non-Gaussian deviations and are able to move in trajectories perpendicular to the collective flow. Thus, cells can maneuver or switch between local streams and jets. A minimal model describing bacteria as hydrodynamic force dipoles shows that steric effects, hydrodynamics interactions, and local alignments all have to be taken into account to explain the observed dynamics. These findings shed light on the physical mechanisms underlying bacterial swarming and the balance between individual and collective dynamics. PMID- 27410752 TI - Physical Mechanisms of Cancer in the Transition to Metastasis. AB - Whether a tumor is metastatic is one of the most significant factors that influence the prognosis for a cancer patient. The transition from a nonmetastatic tumor to a metastatic one is accompanied by a number of genetic and proteomic changes within the tumor cells. These protein-level changes conspire to produce behavioral changes in the cells: cells that had been relatively stationary begin to move, often as a group. In this study we ask the question of what cell-level biophysical changes are sufficient to initiate evasion away from an otherwise static tumor. We use a mathematical model developed to describe the biophysics of epithelial tissue to explore this problem. The model is first validated against in vitro wound healing experiments with cancer cell lines. Then we simulate the behavior of a group of mutated cells within a sea of healthy tissue. We find that moderate increases in adhesion between the cell and extracellular matrix (ECM) accompanied by a decrease in cell-cell adhesion and/or Rho family of small GTPase activation can cause a group of cells to break free from a tumor and spontaneously migrate. This result may explain why some metastatic cells have been observed to upregulate integrin, downregulate cadherin, and activate Rho family signaling. PMID- 27410753 TI - Examining Interpretations of Graphic Cigarette Warning Labels Among U.S. Youth and Adults. AB - Few studies have examined how diverse populations interpret warning labels. This study examined interpretations of 9 graphic cigarette warning labels (image plus text) proposed by the U.S. Food and Drug Administration among a convenience sample of youth (ages 13-17) and adults (18+) across the United States. Participants (N = 1,571) completed a cross-sectional survey. Participants were asked to select 1 of 3 plausible interpretations (1 preferred vs. 2 alternative) created by the research team about the particular consequence of smoking addressed in each warning label. Participants also rated each label for novelty, counterarguing, perceived effectiveness, and harm. Smokers reported their thoughts of quitting, self-efficacy, and motivation to quit. Although at least 70% of the sample chose the preferred interpretation for 7 of 9 labels, only 13% of participants chose all 9 preferred interpretations. The odds of selecting the preferred interpretation were lower among African Americans, among those with less education, and for labels perceived as being more novel. Smokers reported greater counterarguing and less perceived effectiveness and harms than nonsmokers, but results were not consistent across all labels and interpretations. The alternative interpretations of cigarette warning labels were associated with lower perceived effectiveness and lower perceived harms of smoking, both of which are important for motivating quit attempts. PMID- 27410754 TI - [Management of acute postoperative pain following thoracotomy - state of the art]. AB - Postoperative pain management is an important part of complex perioperative care in patients undergoing thoracotomy, irrespective of the procedure type. Adequate pain relief leads to early mobilisation, improves respiratory functions and decreases global stress response. Thus, good perioperative pain management significantly reduces postoperative complications. Currently, numerous analgesic methods are available for the management of acute postthoracotomy pain including patient- or nurse-controlled systemic administration of analgesics, infiltration with local anaesthetics, intrapleural or intercostal nerve blockades and neuroaxial blocks (paravertebral, intrathecal, epidural). The aim of this review is to analyze the currently used methods in postthoracotomy pain management, their benefits in the light of current guidelines, and potential risks. KEY WORDS: thoracotomy - chest surgery analgesia. PMID- 27410755 TI - [The survival of patients with radically non-resectable pancreatic cancer]. AB - INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its poor prognosis is due to a combination of various factors, mainly aggressive biology of the tumour, non-specific symptoms in early stages, their underestimation, prolonged time to diagnosis and late onset of treatment. The majority of patients are diagnosed in an advanced stage of the disease. Median survival of these patients ranges from 211 months. The most common consequences of locally advanced disease that require intervention include obstruction of the duodenum and biliary obstruction. The purpose of our study was to analyze the survival of patients with radically inoperable PDAC undergoing palliative surgery or exploration with biopsy, and to evaluate the influence of patient and tumour factors and treatment modalities on survival. METHODS: In our retrospective study we included all patients with radically inoperable PDAC undergoing a non-radical surgical intervention between 01 January 2006 and 31 December 2014. Patient age, histopathological findings, surgical and oncological treatment and survival were included in the analysis. The results were statistically processed and evaluated using IBM SPSS Statistics software version 22 (USA). RESULTS: 184 patients with radically inoperable PDAC, 105 males and 79 females, were included in our study. Mean age of the patients was 64 years and most patients presented with stage IV of the disease. Mean survival time was 7.04 months and median 4.7 months. CONCLUSION: We determined a statistically significant influence of the following factors on patient survival: sex, stage, presence of distant metastases at the time of surgery and oncological treatment administration. Mean and median survival of patients with radically inoperable tumours matches global statistics. KEY WORDS: pancreatic cancer - radically non resectable - palliative surgery - survival. PMID- 27410756 TI - [Laparoscopic resection rectopexy in the treatment of obstructive defecation syndrome]. AB - INTRODUCTION: Obstructive defecation syndrome (ODS) presents a common medical problem, which can be caused by various pelvic disorders; multiple disorders are frequently diagnosed. At the present, a high number of corrective techniques are available via various surgical approaches. Laparoscopic resection rectopexy is a minimally invasive technique, which comprises redundant sigmoidal resection with rectal mobilisation and fixation. METHODS: The aim of this paper was to evaluate the safety and effectiveness of laparoscopic resection rectopexy in the treatment of patients with ODS. The evaluation was performed via our own patients data analysis and via literature search focused on laparoscopic resection rectopexy. RESULTS: In total, 12 patients with ODS undergoing laparoscopic resection rectopexy in University Hospital Ostrava during the study period (2012-2015) were included in the study. In our study group, mean age was 64.5 years and mean BMI was 21.9; the group included 11 women (91.6%). ODS was caused by multiple pelvic disorders in all patients. Dolichosigmoideum and rectal prolapse (internal or external) were diagnosed in all included patients. On top of that, rectocoele and enterocoele were diagnosed in several patients. Laparoscopic resection rectopexy was performed without intraoperative complications; mean operative time was 144 minutes. Mean postoperative length of hospital stay was 7 days. Postoperative 30 day morbidity was 16.6%. All postoperative complications were classified as grade II according to Clavien-Dindo classification. Mean preoperative Wexner score was 23.6 points; mean score 6 months after the surgery was 11.3 points. Significant improvement in ODS symptoms was noted in 58.3% of patients, and a slight improvement in 16.6% of patients; resection rectopexy provided no clinical effect in 25% of patients. CONCLUSION: It is fundamental to carefully select those patients with ODS who could possibly profit from the surgery. Our results, in accordance with published data, suggest that laparoscopic resection rectopexy is a valuable surgical technique in the treatment of patients with ODS caused by multiple pelvic disorders. KEY WORDS: obstructive defecation syndrome - constipation - resection rectopexy - operative techniques - pelvic floor disorders. PMID- 27410757 TI - [Different techniques of vessel reconstruction in kidney transplantation 10-years experiences]. AB - INTRODUCTION: The aim of the study was to analyze own results from Transplant Center Kosice, Slovak Republic. METHODS: In total 457 patients in the end-stage renal failure were included to the kidney transplant program. Following techniques were used: arterioplasty, individual renal artery anastomosis and multiple renal arteries anastomosed on a common patch. The kidney transplant (Tx) especially requires surgical technique of a vascular anastomosis. RESULTS: Renal transplantation has been established in Transplant Center Kosice since 1988. The arterioplasty of renal artery was performed in 102 (22.3%) and individual artery anastomosis in 25 (5.5%) patients. Multiple artery anastomosis on the patch was done in 43 (9.4%) and implantation of pole renal arteries to the main trunk performed in 34 (7.4%) cases. CONCLUSION: Renal transplantation is a lifesaving method in end stage renal failure. KEY WORDS: kidney transplantation - arterioplasty, cold ischemia time vascular anastomosis. PMID- 27410758 TI - Alveolar echinococcosis - a rare disease with differential diagnostic problems. AB - INTRODUCTION: Alveolar echinococcosis is a life-threatening zoonotic parasitic disease. Its incidence is rare. In some cases, the correct and timely diagnosis can be difficult. CASE REPORT: The authors present the case of a young patient with liver, diaphragm and lung involvement. The suspicion of echinococcus infection was made on the basis of medical history, clinical symptoms, and a combination of ultrasonography, computed tomography, magnetic resonance imaging tests and serological methods. The patient underwent multimodal treatment with albendazole and en-bloc resection of the liver, lung and diaphragm. The definitive diagnosis of alveolar echinococcosis was determined from samples of the resected tissues using histopathology and polymerase chain reaction methods. The patient has been followed regularly and is on life-long treatment with albendazole. CONCLUSION: The precise diagnosis and multimodal therapy of alveolar echinococcosis is fundamental from the point of view of patient long-term survival. KEY WORDS: alveolar echinococcosis - diagnosis - multimodal treatment - follow-up. PMID- 27410759 TI - [Videothoracoscopic excision of mediastinal parathyroid adenoma in primary hyperparathyroidism]. AB - INTRODUCTION: Primary hyperparathyroidism is a disease caused by elevated secretion of parathyroid hormone from pathological parathyroid glands. After the diagnosis, the success of its surgical solution depends predominantly on surgical management and experience of the surgeons. A special group is formed by ectopic localizations of pathologically enlarged parathyroid glands in the mediastinum, which require a modified surgical approach. When the adenoma is deep in the mediastinum, sternotomy or thoracotomy is indicated; alternatively, a minimally invasive approach can be used - videothoracoscopic thymectomy. CASE REPORT: We present a case of a patient with normocalcemic recurrent primary hyperparathyroidism. This patient underwent a minimally invasive video-assisted thymectomy after scintigraphic confirmation of parathyroid adenoma in the mediastinum. CONCLUSION: The removal of parathyroid adenoma in the mediastinum using the videothoracoscopic method is safe. Compared to sternotomy, this method improves the postoperative period, reduces the length of stay and provides more comfort to patients. We recommend considering the videothoracoscopic method in cases where the pathologically enlarged parathyroid gland is localized in the inferior and anterior mediastinum. KEY WORDS: primary hyperparathyroidism adenoma of glandula parathyroidea - mediastinum miniinvasive. PMID- 27410760 TI - [Intraparietal hemorrhage of the small intestine related to hypocoagulation as an unusual cause of hemoperitoneum]. AB - The authors present a case of acute abdomen, spontaneous hemoperitoneum, caused by intraparietal hemorrhage of the small intestine in a patient with hypocoagulation that was pharmacologically induced by warfarin anticoagulation therapy. Potential etiology of the described case is considered by the authors. PMID- 27410761 TI - Neutrophil infiltration and activation in bronchiolitic airways are independent of viral etiology. AB - BACKGROUND: Hospitalization with bronchiolitis is linked to the development of early childhood chronic wheeze and asthma. Viral etiology and severity of inflammation are potential contributing factors. Previously we observed reduced airway neutrophil infiltration in breastfed bronchiolitic infants, with a corresponding reduction in disease severity. This study aimed to examine whether respiratory viral etiology and co-infection alters the pattern of neutrophil influx, and the inflammatory mediator profile, resulting in epithelial damage in bronchiolitis. METHODS: Nasopharyngeal aspirates (NPAs) collected from hospitalized infants were assessed for viruses, soluble protein, cellular infiltrate, interleukin (IL)-6, -8, and myeloperoxidase (MPO). RESULTS: NPAs were collected from 228 bronchiolitic and 14 non-bronchiolitic infants. In the bronchiolitic cohort, human rhinovirus was most prevalent (38%), followed by respiratory syncytial virus (36%), adenovirus (10%), and human metapneumovirus (6%), with 25% positive for viral co-infections and 25% negative for all screened viruses. Viral-induced bronchiolitis was associated with increased cellular infiltrate and protein, above control, and virus-negative infants (P < 0.05). Cellular infiltrate correlated to IL-6, -8, and MPO (r = 0.331, 0.669, and 0.661; P < 0.01). Protein, IL-6, -8, and MPO differed significantly between viral groups; however, the majority of marker values for all groups fall within an overlapping, indistinguishable range, precluding their use as biomarkers of viral etiology. No significant difference was found between single and viral co infections for any parameter. CONCLUSION: Bronchiolitic infants presenting with a detectable respiratory virus during hospitalization demonstrated elevated markers of airway tissue inflammation and injury. In this cohort, viral etiology did not discernibly modulate chemokine-mediated neutrophil infiltration and activation. Pediatr Pulmonol. 2017;52:238-246. (c) 2016 Wiley Periodicals, Inc. PMID- 27410762 TI - Reciprocal Grids: A Hierarchical Algorithm for Computing Solution X-ray Scattering Curves from Supramolecular Complexes at High Resolution. AB - In many biochemical processes large biomolecular assemblies play important roles. X-ray scattering is a label-free bulk method that can probe the structure of large self-assembled complexes in solution. As we demonstrate in this paper, solution X-ray scattering can measure complex supramolecular assemblies at high sensitivity and resolution. At high resolution, however, data analysis of larger complexes is computationally demanding. We present an efficient method to compute the scattering curves from complex structures over a wide range of scattering angles. In our computational method, structures are defined as hierarchical trees in which repeating subunits are docked into their assembly symmetries, describing the manner subunits repeat in the structure (in other words, the locations and orientations of the repeating subunits). The amplitude of the assembly is calculated by computing the amplitudes of the basic subunits on 3D reciprocal space grids, moving up in the hierarchy, calculating the grids of larger structures, and repeating this process for all the leaves and nodes of the tree. For very large structures, we developed a hybrid method that sums grids of smaller subunits in order to avoid numerical artifacts. We developed protocols for obtaining high-resolution solution X-ray scattering data from taxol-free microtubules at a wide range of scattering angles. We then validated our method by adequately modeling these high-resolution data. The higher speed and accuracy of our method, over existing methods, is demonstrated for smaller structures: short microtubule and tobacco mosaic virus. Our algorithm may be integrated into various structure prediction computational tools, simulations, and theoretical models, and provide means for testing their predicted structural model, by calculating the expected X-ray scattering curve and comparing with experimental data. PMID- 27410763 TI - New antibiotics in clinical trials for Clostridium difficile. AB - INTRODUCTION: There are limited number of approved therapies for C. difficile infections (CDIs) and new treatments are needed to decrease recurrence rates. Over the past 5 years, four novel antibiotics have been evaluated in clinical trials that offer distinct advantages over existing therapies for the treatment of CDI. AREAS COVERED: This article reviews the preclinical and clinical studies of cadazolid, LFF571, ridinilazole, and surotomycin. The advantages that these antibiotics may have in the treatment of CDI is compared with current therapies metronidazole, vancomycin, and fidaxomicin. Expert commentary: The antibiotics examined have the potential to improve rates of CDI treatment without recurrence. We anticipate that one or more of these medications will be approved within five years. PMID- 27410764 TI - Midlife and older women's experiences and advice about sex with men, risk behaviors, and HIV prevention education. AB - This article reports on older women's experiences and advice on condom use, male female relationships, HIV risk, and prevention education. It reports on findings from five written, open-ended questions with 110 ethnically and economically diverse women, 40-80 years old. Analysis revealed four themes: (a) Gap between condom use advice and condom use behavior; (b) invisibility with age; (c) negative expectations of men; and (d) desire for education that breaks the silence on sex. The article discusses the meaning of the findings as they relate to current knowledge about HIV prevention education and midlife and older women and offers recommendations for research and education. PMID- 27410765 TI - Electrochemical Rectification of Redox Mediators Using Porphyrin-Based Molecular Multilayered Films on ITO Electrodes. AB - Electrochemical charge transfer through multilayer thin films of zinc and nickel 5,10,15,20-tetra(4-ethynylphenyl) porphyrin constructed via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry was examined. Current rectification toward various outer-sphere redox probes is revealed with increasing numbers of layers, as these films possess insulating properties over the neutral potential range of the porphyrin, then become conductive upon reaching its oxidation potential. Interfacial electron transfer rates of mediator dye interactions toward [Co(bpy)3](2+), [Co(dmb)3](2+), [Co(NO2-phen)3](2+), [Fe(bpy)3](2+), and ferrocene (Fc), all outer-sphere redox species, were measured by hydrodynamic methods. The ability to modify electroactive films' interfacial electron transfer rates, as well as current rectification toward redox species, has broad applicability in a number of devices, particularly photovoltaics and photogalvanics. PMID- 27410766 TI - Profiling Sprint Mechanics by Leg Preference and Position in Rugby Union Athletes. AB - Lower-extremity power characteristics are central to performance in rugby. However little is known regarding the effects of leg preference and playing position on sprint mechanics. The purpose of this study was to profile sprint kinetics and kinematics in rugby union athletes and compare between legs and between positions. Thirty male academy-level rugby union athletes, separated into forwards (n=15) and backs (n=15), participated in this cross-sectional analysis. Non-motorised treadmill ergometry was used to evaluate peak relative vertical (FV) and horizontal (FH) force and peak relative power (Pmax) of the preferred and non-preferred legs during maximal sprinting. The non-preferred leg of the forwards produced less FV, FH and Pmax than the preferred leg during acceleration (ES=-0.32, - 0.58 and - 0.67) and maximal velocity (ES=- 0.50, - 0.65 and - 0.60). Backs produced more FV, FH and Pmax than the forwards during initial acceleration (ES=0.51, 1.58 and 1.30) but less at maximal velocity (ES=- 0.74, 0.79 and - 0.81). Backs had faster split times at 2, 5, 10 and 15 m (ES=-1.03, 0.82, -0.63 and -0.50) but slower times at 35 and 40 m (ES=0.78 and 1.10) compared with forwards. Forwards produced larger sprint kinetics compared with backs, but also larger lower-extremity imbalances; potentially reducing sprint efficiency and/or increasing injury risk. PMID- 27410767 TI - Reliability of the Three-minute All-out Test for Non-motorized Treadmill Tethered Running. AB - The 3-min all-out test was developed and validated on a cycle ergometer using a modification of a linear mathematical equation (1/time vs. power) obtained from the original critical power model. The purpose of this development was to obtain, in a single test, the aerobic and anaerobic capacity parameters and identify the exercise transition moment from heavy to severe intensity. The aim of this study was to propose an adaptation of the all-out 3-min cycle ergometer to a non motorized treadmill with tethered running. In addition, we tested the reproducibility of this adapted protocol, highlighting the need for mechanical power evaluation using a specific ergometer. Consequently, 10 physically active individuals visited the laboratory 4 times for testing and data collection. The results suggested that the protocol adaptation for the 3-min all-out test for non motorized treadmill with tethered running was reproducible and feasible. It was also possible to show that the AO3 application in this ergometer ensures the specificity of the sports that involve the running exercise, from assessment of both aerobic and anaerobic parameters, accomplished in a single day of application. PMID- 27410769 TI - Effect of High and Low Flexibility Levels on Physical Fitness and Neuromuscular Properties in Professional Soccer Players. AB - This study aimed to analyse the impact of high and low flexibility levels of hamstring and quadriceps muscles on physical fitness and neuromuscular properties in professional soccer players. 62 male professional soccer players participated in this study and performed 2 instrumented flexibility tests (passive straight leg raise [PSLR] and quadriceps flexibility [QF]). Anaerobic performance was assessed using countermovement jump (CMJ), Abalakov vertical jump, 20-m sprint, and Balsom agility test. A k-means cluster analysis was performed to identify a cut-off value of hamstring and quadriceps flexibility and classify players as high hamstring flexibility (HHF) and low hamstring flexibility (LHF) or high quadriceps flexibility (HQF) and low quadriceps flexibility (LQF), respectively, according to the PSLR and QF performances. The LQF players performed better than HQF on CMJ (p=0.042, ES: 0.64) and Balsom agility test (p=0.029, ES: 0.68). In addition, LQF showed higher muscular stiffness than HQF players (p=0.002, ES: 0.88). There were no significant differences between HHF and LHF groups. When pooling the HQF and LQF players' data, the Pearson's correlation showed significant moderate positive association between muscular stiffness and QF (r=0.516, p<0.001). These results support the rationale that baseline stiffness is likely to influence athletic performance rather than flexibility level in soccer players. PMID- 27410768 TI - Cross-validation of Peak Oxygen Consumption Prediction Models From OMNI Perceived Exertion. AB - This study cross-validated statistical models for prediction of peak oxygen consumption using ratings of perceived exertion from the Adult OMNI Cycle Scale of Perceived Exertion. 74 participants (men: n=36; women: n=38) completed a graded cycle exercise test. Ratings of perceived exertion for the overall body, legs, and chest/breathing were recorded each test stage and entered into previously developed 3-stage peak oxygen consumption prediction models. There were no significant differences (p>0.05) between measured and predicted peak oxygen consumption from ratings of perceived exertion for the overall body, legs, and chest/breathing within men (mean+/-standard deviation: 3.16+/-0.52 vs. 2.92+/ 0.33 vs. 2.90+/-0.29 vs. 2.90+/-0.26 L.min(-1)) and women (2.17+/-0.29 vs. 2.02+/ 0.22 vs. 2.03+/-0.19 vs. 2.01+/-0.19 L.min(-1)) participants. Previously developed statistical models for prediction of peak oxygen consumption based on subpeak OMNI ratings of perceived exertion responses were similar to measured peak oxygen consumption in a separate group of participants. These findings provide practical implications for the use of the original statistical models in standard health-fitness settings. PMID- 27410770 TI - Ten Days of Intermittent, Low-dose Carbon Monoxide Inhalation does not Significantly Alter Hemoglobin Mass, Aerobic Performance Predictors, or Peak power Exercise Tolerance. AB - Carbon monoxide (CO) rebreathing procedures are used to assess hemoglobin mass (Hbmass) but recent evidence suggests that CO is a signaling molecule that may alter physiological functions. We examined the effects of 10 days of intermittent, low-dose CO inhalation on Hbmass, aerobic performance predictors, and peak-power exercise tolerance. 18 recreationally-active men were randomized to either CO or placebo inhalation groups in a single-blind, pre-post parallel groups trial. Primary outcomes were assessed before and after an intervention period during which subjects inhaled a bolus of 1.2 ml kg(-1) CO or placebo (room air) for 30 s, once per day on 10 days over a 12-day period. Cycling tests were performed >16 h following CO inhalation to exclude acute effects of CO exposure. CO inhalation elevated carboxyhemoglobin by 4.4+/-0.4% (mean+/-SD) following each exposure. Compared to placebo, chronic CO inhalation did not significantly alter Hbmass (p=0.99), peak oxygen uptake (p=0.59), peak power output (p=0.10), submaximal oxygen uptake (p=0.91), submaximal RER (p=0.22), lactate threshold (p=0.65), or peak-power exercise tolerance (p=0.60). In conclusion, our data support the ability to perform repeated measurements of Hbmass using CO rebreathing over a 12-day period without altering physiological responses. PMID- 27410771 TI - A central role of H3K4me3 extended chromatin domains in gene regulation. PMID- 27410772 TI - Quantitative Endoscopic Phototransducer Investigation of Normal Velopharyngeal Physiology. AB - PURPOSE: The purpose of this research was to learn the extent to which healthy individuals vary in their ability to achieve velopharyngeal closure for speech. METHOD: Twenty healthy adult volunteers (10 women, 10 men) were tested using an endoscopic phototransducer system that tracks variations in velopharyngeal closure during speech production. Each speaker produced multiple repetitions of three utterances that differed in phonetic content. The data were amplitude normalized and averaged for each speaker. RESULTS: Average phototransducer measurements were similar across subjects for utterances containing only oral phonemes. Average percentage of velopharyngeal closure varied considerably among subjects when producing utterances containing both oral and nasal phonemes (54% 95%). Average percentage of velopharyngeal closure levels were significantly lower (p < .05) for utterances that included nasal consonants. CONCLUSIONS: Phototransducer measurements of velopharyngeal closure for speech are sensitive to nasal phoneme content. The findings suggest that motor programming that accomplishes rapid oral-nasal velopharyngeal valving for speech may differ among healthy subjects. However, such variations in motor programming may not perceptually affect typical speakers. If present in individuals with abnormal velopharyngeal mechanisms, these variations may help explain variations among speakers in speech outcomes after physical and behavioral management. PMID- 27410773 TI - Clinical platform for understanding the relationship between joint contact mechanics and articular cartilage changes after meniscal surgery. AB - Injury to the meniscus of the knee has been implicated as a significant risk factor for the subsequent development of osteoarthritis, but the mechanisms of joint degeneration are unclear. Our objective was to develop a clinically applicable methodology to evaluate the relationship of joint contact mechanics at the time of surgery to biological changes of articular cartilage as a function of time following surgery. A series of pre-, intra-, and post-operative protocols were developed which utilized electronic sensors for the direct measurement of contact mechanics, and advanced imaging to assess cartilage health. The tests were applied to a pilot cohort of young active patients undergoing meniscus allograft transplantation. Our study demonstrated significant variability across patients in terms of contact area and peak contact stress, both before and after transplantation. Nonetheless, the majority of patients exhibited decreased peak contact stress and increased contact area after graft implantation. MR scans at 3 6 months showed decreased T1rho values in tibial articular cartilage, suggesting an increase in proteoglycan content or concomitant decrease in water content. Prolongation of T2 values was found primarily within the central, cartilage cartilage contact region of the tibial plateau suggested disruption of the collagen network. Minimal differences were found in cartilage thickness over the short time frame of this preliminary study. With longer clinical follow-up, our platform of clinical tests can be used to better understand the patient-specific mechanical factors that are related to increased risk of OA after meniscus injury and surgery. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:600-611, 2017. PMID- 27410774 TI - Sleep Disordered Breathing During Live High-Train Low in Normobaric Versus Hypobaric Hypoxia. AB - Saugy, Jonas J., Laurent Schmitt, Sibylle Fallet, Raphael Faiss, Jean-Marc Vesin, Mattia Bertschi, Raphael Heinzer, and Gregoire P. Millet. Sleep disordered breathing during live high-train low in normobaric versus hypobaric hypoxia. High Alt Med Biol. 17:233-238, 2016.-The present study aimed to compare sleep disordered breathing during live high-train low (LHTL) altitude camp using normobaric hypoxia (NH) and hypobaric hypoxia (HH). Sixteen highly trained triathletes completed two 18-day LHTL camps in a crossover designed study. They trained at 1100-1200 m while they slept either in NH at a simulated altitude of 2250 m or in HH. Breathing frequency and oxygen saturation (SpO2) were recorded continuously during all nights and oxygen desaturation index (ODI 3%) calculated. Breathing frequency was lower for NH than HH during the camps (14.6 +/- 3.1 breath * min-1 vs. 17.2 +/- 3.4 breath * min-1, p < 0.001). SpO2 was lower for HH than NH (90.8 +/- 0.3 vs. 91.9 +/- 0.2, p < 0.001) and ODI 3% was higher for HH than NH (15.1 +/- 3.5 vs. 9.9 +/- 1.6, p < 0.001). Sleep in moderate HH is more altered than in NH during a LHTL camp. PMID- 27410775 TI - Body roundness index and body adiposity index: two new anthropometric indices to identify metabolic syndrome among Chinese postmenopausal women. AB - OBJECTIVES: Body roundness index (BRI) and body adiposity index (BAI) have been recently proposed to assess obesity. The objectives of this cross-sectional study were to compare their potential for identifying metabolic syndrome (MetS) with traditional obesity indices in Chinese postmenopausal women. METHODS: A total of 817 participants were involved in this study. Odds ratio and corresponding 95% confidence intervals (CI) between MetS and all indices were evaluated by binary logistic regression analysis. Receiver operating characteristic curve and area under curve (AUC) were employed to evaluate the abilities to identify MetS among all the indices. The differences in the AUC values between traditional indices and BAI as well as BRI were also evaluated. RESULTS: The upper values of all indices were significantly associated with the presence of MetS after adjusting for potential confounders, except for BAI. There were no significant differences in the AUC values between BRI and the traditional indices; however, the AUC values of all the traditional indices were significantly larger than that of BAI. CONCLUSIONS: Neither BAI nor BRI was superior to traditional obesity indices for predicting MetS. BAI showed the weakest predictive ability, while BRI showed potential for use as an alternative obesity measure in assessment of MetS. PMID- 27410776 TI - Identification of molecular descriptors for design of novel Isoalloxazine derivatives as potential Acetylcholinesterase inhibitors against Alzheimer's disease. AB - In Alzheimer's disease (AD), the level of Acetylcholine (ACh) neurotransmitter is reduced. Since Acetylcholinesterase (AChE) cleaves ACh, inhibitors of AChE are very much sought after for AD treatment. The side effects of current inhibitors necessitate development of newer AChE inhibitors. Isoalloxazine derivatives have proved to be promising (AChE) inhibitors. However, their structure-activity relationship studies have not been reported till date. In the present work, various quantitative structure-activity relationship (QSAR) building methods such as multiple linear regression (MLR), partial least squares ,and principal component regression were employed to derive 3D-QSAR models using steric and electrostatic field descriptors. Statistically significant model was obtained using MLR coupled with stepwise selection method having r2 = .9405, cross validated r2 (q2) = .6683, and a high predictability (pred_r2 = .6206 and standard error, pred_r2se = .2491). Steric and electrostatic contribution plot revealed three electrostatic fields E_496, E_386 and E_577 and one steric field S_60 contributing towards biological activity. A ligand-based 3D-pharmacophore model was generated consisting of eight pharmacophore features. Isoalloxazine derivatives were docked against human AChE, which revealed critical residues implicated in hydrogen bonds as well as hydrophobic interactions. The binding modes of docked complexes (AChE_IA1 and AChE_IA14) were validated by molecular dynamics simulation which showed their stable trajectories in terms of root mean square deviation and molecular mechanics/Poisson-Boltzmann surface area binding free energy analysis revealed key residues contributing significantly to overall binding energy. The present study may be useful in the design of more potent Isoalloxazine derivatives as AChE inhibitors. PMID- 27410777 TI - On the mechanism of Ni(ii)-promoted Michael-type hydroamination of acrylonitrile and its substituted derivatives. AB - Michael-type hydroamination of acrylonitrile and its substituted derivatives promoted by Ni(ii) complexes is believed to proceed via an outer-sphere nucleophilic attack on the cationic adduct of the nitrile-coordinated substrate. As a test for the validity of this mechanistic postulate, we have sought to establish a correlation between the electrophilic character of the Ni(ii) center and the degree to which it can activate the substrate toward nucleophilic attack by amines. This has been done by screening the catalytic activities of the cationic acetonitrile adducts [(R-POCOP)Ni(NCCH3)][OSO2CF3] bearing an electron donating or electron-withdrawing substituent R on the central aromatic ring of the POCOP ligand (R-POCOP = kappaP,kappaC,kappaP-2,6-(i-Pr2PO)2-4-R-C6H2; R = OMe (3), COOMe (4)). The catalytic activities for the addition of primary amines to crotonitrile, methacrylonitrile, and cinnamonitrile were found to depend on the precursor and the amine used, as well as on the reaction time. These studies were complemented by ligand exchange studies that established the relative binding order among the main components of a typical hydroamination mixture (RCN > amine > OSO2CF3), thus supporting the assertion that cationic nitrile adducts constitute the resting state in the catalytic manifold. We have also prepared and characterized the cationic acrylonitrile and cinnamonitrile adducts [(R POCOP)Ni(NCCH[double bond, length as m-dash]CHR')][OSO2CF3] (R' = H: R = COOMe (7) or OMe (8); R' = Ph: R = COOMe (9) or OMe (10)) as models of the postulated catalytic intermediates in the addition of amines to these substrates. To allow structural comparisons to the nitrile adducts, we have prepared and characterized the ammonia adducts [(R-POCOP)Ni(NH3)][OSO2CF3] (R = H, 11, and COOMe, 12). The results of structural, spectroscopic, and reactivity studies carried out on these compounds and their implications for the mechanism of Michael-type hydroamination reactions promoted by the title system have been discussed. PMID- 27410780 TI - Coming in postgraduate medicine. PMID- 27410778 TI - Identification of novel candidate regulators of retinotectal map formation through transcriptional profiling of the chick optic tectum. AB - Information from the retina is carried along the visual pathway with accuracy and spatial conservation as a result of topographically mapped axonal connections. The optic tectum in the midbrain is the primary region to which retinal ganglion cells project their axons in the chick. The two primary axes of the retina project independently onto the tectum using different sets of guidance cues to give rise to the retinotectal map. Specificity of the map is determined by attractive or repulsive interactions between molecular tags that are distributed in gradients in the retina and the tectum. Despite several studies, knowledge of the retinotectal guidance molecules is far from being complete. We screened for all molecules that are expressed differentially along the anterior-posterior and medial-lateral axes of the chick tectum using microarray based transcriptional profiling and identified several novel candidate retinotectal guidance molecules. Two such genes, encoding Wnt5a and Raldh2, the synthesizing enzymes for retinoic acid, were further analyzed for their function as putative regulators of retinotectal map formation. Wnt5a and retinoic acid were found to exhibit differential effects on the growth of axons from retinal explants derived from different quadrants of the retina. This screen also yielded a large number of genes expressed in a lamina-specific manner in the tectum, which may have other roles in tectal development. J. Comp. Neurol. 525:459-477, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27410779 TI - Group 14 Dithienometallole-Linked Ethynylene-Conjugated Porphyrin Dimers. AB - The considerably conjugated pi systems of the group 14 dithienometallole-linked ethynylene-conjugated porphyrin dimers (1Ms) were described based on comprehensive experimental and theoretical studies. The electronic absorption spectra of 1M displayed a large splitting in the Soret band and a red-shifted Q band, indicating that the dithienometallole spacer was effective in facilitating the porphyrin-porphyrin electronic coupling. Torsional planarization behaviors of 1M were observed in the time-resolved fluorescence spectra. Density functional theory (DFT) calculations revealed that the dithienometallole spacer is an ideal partner for the ethynylene-conjugated porphyrin to produce fully delocalized highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels due to their similar HOMO and LUMO levels. Finally, 1M exhibited a strong propensity for the quinoidal-cummulenic conjugation in the dithienometallole spacer when in a photoexcited state. PMID- 27410781 TI - Editor's mail. PMID- 27410782 TI - Problems solutions. PMID- 27410783 TI - What's happening in medicine. PMID- 27410784 TI - Washington background. PMID- 27410785 TI - Physician-at-large. PMID- 27410787 TI - Glossary of Abbreviations Used in This Symposium. PMID- 27410786 TI - Introduction. PMID- 27410788 TI - Indications for Thyroid Surgery. PMID- 27410789 TI - Self-test on Thyroid Manacement. PMID- 27410790 TI - ReadySource on Thyroid Management. PMID- 27410791 TI - A Pamphlet for Patients. PMID- 27410793 TI - Therapeutic Index to Advertisers. PMID- 27410795 TI - Enhancement of light-matter interaction and photocatalytic efficiency of Au/TiO2 hybrid nanowires. AB - Metal/TiO2 hybrid nanostructures offer more efficient charge separation and a broader range of working wavelengths for photocatalytic reactions. The sizes and shapes of such hybrid nanostructures can affect the charge separation performance when the structures interact with light, but assessments of the interaction of light with these metal-TiO2 nanostructures have only been carried out on ensemble averages, hindering both systematic descriptions of such hybrid structures and the design of new ones. Here, we fabricated TiO2 nanotubes (NTs) with and without core Au nanowires (NWs), and used spectroscopy and calculations to assess their scattering and absorption of light at the single NW level. According to the results of spectral imaging and numerical calculations, the Au/TiO2 NWs scattered and absorbed light substantially more strongly than did the plain TiO2 NTs. Measurements of the degradation of the AO7 dye to assess the photocatalytic performance of the Au/TiO2 NWs were consistent with optical measurements demonstrating a two-fold improvement over plain TiO2 NTs under 360-nm-wavelength UV illumination. Our results suggests that nanoscale optical imaging can be used to visualize the performance of the photocatalytic reaction at the single nano-object level. PMID- 27410794 TI - A Single Fluorescent Probe to Visualize Hydrogen Sulfide and Hydrogen Polysulfides with Different Fluorescence Signals. AB - Hydrogen sulfide (H2 S) and hydrogen polysulfides (H2 Sn , n>1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross-talk between H2 S and H2 Sn , it is highly desirable to develop single fluorescent probes which enable dual-channel discrimination between H2 S and H2 Sn . Herein, we report the rational design, synthesis, and evaluation of the first dual-detection fluorescent probe DDP-1 that can visualize H2 S and H2 Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2 S and H2 Sn in aqueous media and in cells. PMID- 27410796 TI - Mid-infrared-pumped quantum cascade structure for high-sensitive terahertz detection. AB - Based on multiple quantum wells, we design a pumping-detection quantum cascade structure for the detection of terahertz (THz) radiation. In the structure, carriers are first pumped by a mid-infrared (MIR) laser to an excited state, to get enough energy space for the following fast longitudinal optical (LO) phonon extraction. Within the LO-phonon extraction stair, an absorption well is designed for THz detection. Due to the establishment of LO-phonon stair extractor, carriers transport between quantum wells in picosecond range and a high responsivity for THz absorption can be obtained. We also find that doping in both MIR active well and extractor region is significant for high-speed response of the THz detection. Our design is expected to extend the high-sensitive detection of a quantum cascade photodetector from middle wave of MIR to THz region. PMID- 27410797 TI - Influence of focal point properties on energy transfer and plasma evolution during laser ignition process with a passively q-switched laser. AB - Miniaturized passively q-switched laser ignition systems are a promising alternative to conventional ignition sources to ensure a reliable ignition under difficult conditions. In this study the influences of focal point properties on energy transfer from laser to plasma as well as plasma formation and propagation are investigated as the first steps of the laser induced ignition process. Maximum fluence and fluence volume are introduced to characterize focal point properties for varying laser pulse energies and focusing configurations. The results show that the transferred laser energy increases with increasing maximum fluence. During laser emission plasma propagates along the beam path of the focused laser beam. Rising maximum fluence results in increased plasma volume, but expansion saturates when fluence volume reaches its maximum. PMID- 27410798 TI - Octave-band tunable optical vortex parametric oscillator. AB - We developed an octave-band tunable optical vortex laser based on a 532 nm optical vortex pumped optical parametric oscillator with a simple linear-cavity configuration by employing cascaded non-critical phase-matching LiB3O5 crystals. The optical vortex output was tunable from 735 to 1903 nm. For a pump energy of 9 mJ, an optical vortex pulse energy of 0.24 2.36 mJ was obtained, corresponding to an optical-optical efficiency of 0.3-26%. PMID- 27410799 TI - Investigation of optical pump on dielectric tunability in PZT/PT thin film by THz spectroscopy. AB - The dielectric spectra of single-layer PbTiO3 (PT), single-layer PbZrxTi1-xO3 (PZT) and multilayer PZT/PT thin films under an external optical field were investigated at room temperature by time-domain terahertz (THz) spectroscopy. Results showed that the real part of permittivity increased upon application of an external optical field, which could be interpreted as hardening of the soft mode and increasing of the damping coefficient and oscillator strength. Furthermore, the central mode was observed in the three films. Among the dielectric property of the three thin films studied, the tunability of the PZT/PT superlattice was the largest. PMID- 27410800 TI - Increasing the effective aperture of a detector and enlarging the receiving field of view in a 3D imaging lidar system through hexagonal prism beam splitting. AB - The detector in a highly accurate and high-definition scanning 3D imaging lidar system requires high frequency bandwidth and sufficient photosensitive area. To solve the problem of small photosensitive area of an existing indium gallium arsenide detector with a certain frequency bandwidth, this study proposes a method for increasing the receiving field of view (FOV) and enlarging the effective photosensitive aperture of such detector through hexagonal prism beam splitting. The principle and construction of hexagonal prism beam splitting is also discussed in this research. Accordingly, a receiving optical system with two hexagonal prisms is provided and the splitting beam effect of the simulation experiment is analyzed. Using this novel method, the receiving optical system's FOV can be improved effectively up to +/-5 degrees , and the effective photosensitive aperture of the detector is increased from 0.5 mm to 1.5 mm. PMID- 27410801 TI - Vector Hermite-Gaussian correlated Schell-model beam. AB - A new kind of partially coherent vector beam named vector Hermite-Gaussian correlated Schell-model (HGCSM) beam is introduced as a natural extension of recently introduced scalar HGCSM beam. The realizability and beam conditions for a vector HGCSM beam with uniform state of polarization (SOP) or non-uniform SOP are derived, respectively. Furthermore, analytical formulae for a vector HGCSM beam propagating in free space are derived, and the propagation properties of a vector HGCSM beam with uniform SOP or non-uniform SOP in free space are studied and analyzed in detail. We find that the behaviors of a vector HGCSM beam on propagation are quite different from those of a conventional vector partially coherent beam with uniform SOP or non-uniform SOP, and modulating the structures of the correlation functions cannot only modulate the intensity distribution, but also the state of polarization, the degree of polarization and the polarization singularities of a partially coherent vector beam on propagation. Furthermore, we report experimental generation of a radially polarized HGCSM beam for the first time. Our results provide a novel way for polarization modulation. PMID- 27410802 TI - Rogue-wave bullets in a composite (2+1)D nonlinear medium. AB - We show that nonlinear wave packets localized in two dimensions with characteristic rogue wave profiles can propagate in a third dimension with significant stability. This unique behavior makes these waves analogous to light bullets, with the additional feature that they propagate on a finite background. Bulletlike rogue-wave singlet and triplet are derived analytically from a composite (2+1)D nonlinear wave equation. The latter can be interpreted as the combination of two integrable (1+1)D models expressed in different dimensions, namely, the Hirota equation and the complex modified Korteweg-de Vries equation. Numerical simulations confirm that the generation of rogue-wave bullets can be observed in the presence of spontaneous modulation instability activated by quantum noise. PMID- 27410803 TI - Saturable absorption of femtosecond optical pulses in multilayer turbostratic graphene. AB - We investigate the nonlinear transmission of a ~280-layer turbostratic graphene sheet for near-infrared amplifier laser pulses (775 nm, Ti:sapphire laser) with a duration of 150-fs and 20-fs. Saturable absorption is observed in both cases, however it is not very strong, amounting to ~13% transmittance change for the 20 fs (150-fs) pulses at a peak intensity of 30 GW/cm2 (4 GW/cm2). The dependence on incident peak intensity is reproduced well using a theoretical model for the time-dependent saturable absorption, where the excited carriers vacate the photo-excited energy range within 3-5 fs, which we attribute to energy redistribution due to carrier-carrier scattering. This is also supported by spectrally resolved measurements for the 20-fs pulses, which show a marked dependence of the degree of saturation on the photon energy. A key result is that the shorter pulses do not yield a lower saturation fluence, due to the combined effects of the broader excitation bandwidth, and the rapid and broad energy redistribution. We also predict the potential performance of multilayer graphene samples for removing pedestal and pre-pulse structure from ultrafast high-energy pulses. PMID- 27410804 TI - Dynamic gain aperture modelocking in picosecond regime based on cascaded second order nonlinearity. AB - The operation of a cascaded second-order mode-locked Nd:YVO4 laser has been investigated considering it as a soft-aperture Kerr lens type and using complex beam parameters. A self consistent complex beam propagation method is used to incorporate the effect of cascaded Kerr nonlinearity on radially varying gain aperturing. The analysis deduces a stable pulsewidth of ~9.5 ps which agrees well with the experimental value of 10.3 ps. PMID- 27410805 TI - Preparation and luminescence properties of ZnO:Ga - polystyrene composite scintillator. AB - Highly luminescent ZnO:Ga-polystyrene composite (ZnO:Ga-PS) with ultrafast subnanosecond decay was prepared by homogeneous embedding the ZnO:Ga scintillating powder into the scintillating organic matrix. The powder was prepared by photo-induced precipitation with subsequent calcination in air and Ar/H2 atmospheres. The composite was subsequently prepared by mixing the ZnO:Ga powder into the polystyrene (10 wt% fraction of ZnO:Ga) and press compacted to the 1 mm thick pellet. Luminescent spectral and kinetic characteristics of ZnO:Ga were preserved. Radioluminescence spectra corresponded purely to the ZnO:Ga scintillating phase and emission of polystyrene at 300-350 nm was absent. These features suggest the presence of non-radiative energy transfer from polystyrene host towards the ZnO:Ga scintillating phase which is confirmed by the measurement of X-ray excited scintillation decay with picosecond time resolution. It shows an ultrafast rise time below the time resolution of the experiment (18 ps) and a single-exponential decay with the decay time around 500 ps. PMID- 27410806 TI - Tunable and switchable dual-wavelength mode-locked Tm3+-doped fiber laser based on a fiber taper. AB - We demonstrate a self-starting dual-wavelength mode-locked fiber laser at a 2 MUm spectral region by using a fiber taper in a Tm3+-doped ring fiber cavity. The fiber taper fabricated with a flame brushing technique was used as a periodic filter with a modulation depth of ~3.61 dB and a modulation period of ~7.3 nm, respectively. Diverse dual-wavelength regimes including continuous wave (CW)/multi-soliton, soliton/multi-soliton, and soliton/soliton regimes were obtained by adjusting pump power. Wavelength tuning for the dual-wavelength was also precisely controllable through stretching the fiber taper carefully. The tuning range was ~7 nm which was limited by the modulation period of the taper. By inserting a 10.0 m dispersion compensation fiber (DCF) into the fiber cavity, a stable dual-wavelength dissipative-soliton operation was obtained at 2 MUm spectral region for the first time. PMID- 27410807 TI - Diffractive control of 3D multifilamentation in fused silica with micrometric resolution. AB - We show that a simple diffractive phase element (DPE) can be used to manipulate at will the positions and energy of multiple filaments generated in fused silica under femtosecond pulsed illumination. The method allows obtaining three dimensional distributions of controlled filaments whose separations can be in the order of few micrometers. With such small distances we are able to study the mutual coherence among filaments from the resulted interference pattern, without needing a two-arm interferometer. The encoding of the DPE into a phase-only spatial light modulator (SLM) provides an extra degree of freedom to the optical set-up, giving more versatility for implementing different DPEs in real time. Our proposal might be particularly suited for applications at which an accurate manipulation of multiple filaments is required. PMID- 27410808 TI - Deterministic conversion of a four-photon GHZ state to a W state via homodyne measurement. AB - We propose a specific method for converting a four-photon Greenberger-Horne Zeilinger (GHZ) state to a W state in a deterministic way by using linear optical elements, cross-Kerr nonlinearities, and homodyne measurement. We consider the effects of the quadrature homodyne measurements on the fidelity of the W state and the experimental feasibility of the proposed scheme. This might provide great prospects for converting multipartite entangled states into each other for future optical quantum information processing (QIP). PMID- 27410809 TI - Self-phase modulation enabled, wavelength-tunable ultrafast fiber laser sources: an energy scalable approach. AB - We propose and demonstrate a new approach to implement a wavelength-tunable ultrafast fiber laser source suitable for multiphoton microscopy. We employ fiber optic nonlinearities to broaden a narrowband optical spectrum generated by an Yb fiber laser system and then use optical bandpass filters to select the leftmost or rightmost spectral lobes from the broadened spectrum. Detailed numerical modeling shows that self-phase modulation dominates the spectral broadening, self steepening tends to blue shift the broadened spectrum, and stimulated Raman scattering is minimal. We also find that optical wave breaking caused by fiber dispersion slows down the shift of the leftmost/rightmost spectral lobes and therefore limits the wavelength tuning range of the filtered spectra. We show both numerically and experimentally that shortening the fiber used for spectral broadening while increasing the input pulse energy can overcome this dispersion induced limitation; as a result, the filtered spectral lobes have higher power, constituting a powerful and practical approach for energy scaling the resulting femtosecond sources. We use two commercially available photonic crystal fibers to verify the simulation results. More specific, use of 20-mm fiber NL-1050-ZERO-2 enables us to implement an Yb-fiber laser based ultrafast source, delivering femtosecond (70-120 fs) pulses tunable from 825 nm to 1210 nm with >1 nJ pulse energy. PMID- 27410810 TI - Short-pulse actively Q-switched Er:YAG lasers. AB - We report the shortest duration pulses obtained to date from an actively Q switched Er:YAG laser pumped by a low spectral and spatial brightness laser diode. The 14.5 ns, 6 mJ pulses were obtained using a 1470 nm laser diode end pumped co-planar folded zigzag slab architecture. We also present an analytical model that accurately predicts the pulse energy-duration product achievable from virtually all Q-switched Er:YAG lasers and high repetition rate quasi-three-level Q-switched lasers in general. PMID- 27410811 TI - Tunable triple Fano resonances based on multimode interference in coupled plasmonic resonator system. AB - In this paper, an asymmetric plasmonic structure composed of two MIM (metal insulator-metal) waveguides and two rectangular cavities is reported, which can support triple Fano resonances originating from three different mechanisms. And the multimode interference coupled mode theory (MICMT) including coupling phases is proposed based on single mode coupled mode theory (CMT), which is used for describing and explaining the multiple Fano resonance phenomenon in coupled plasmonic resonator systems. Just because the triple Fano resonances originate from three different mechanisms, each Fano resonance can be tuned independently or semi-independently by changing the parameters of the two rectangular cavities. Such, a narrow 'M' type of double Lorentzian-like line-shape transmission windows with the position and the full width at half maximum (FWHM) can be tuned freely is constructed by changing the parameters of the two cavities appropriately, which can find widely applications in sensors, nonlinear and slow-light devices. PMID- 27410812 TI - Nanoimprint-defined, large-area meta-surfaces for unidirectional optical transmission with superior extinction in the visible-to-infrared range. AB - Optical devices with asymmetric transmission have important applications in optical systems, but optical isolators with the modal asymmetry can only be built using magneto-optical or nonlinear materials, as dictated by the Lorentz reciprocity theorem. However, optical devices with the power asymmetry can be achieved by linear materials such as metals and dielectrics. In this paper, we report a large-area, nanoimprint-defined meta-surface (stacked subwavelength gratings) with high-contrast asymmetric transmittance in the visible-to-infrared wavelength range for TM-polarized light. The physical origin of asymmetric transmission through the meta-surface is studied by analyzing the scattering matrix. PMID- 27410813 TI - Design and numerical study of a compact, broadband and low-loss TE-pass polarizer using transparent conducting oxides. AB - A compact, broadband, and low-loss TE-pass polarizer using transparent conducting oxides (TCOs) embedded in the center of the strip waveguide and deposited on its top is proposed and analyzed in detail. With the tunable permittivity of TCO, epsilon-near-zero (ENZ) of its real part and significant increase of its imaginary part can be achieved around the wavelength of 1.55 MUm under a certain electron concentration. By introducing this ENZ material into the strip waveguide, huge polarization dependence can be realized, that is, the TE mode is almost not affected due to its quite weak interaction with TCOs, while the TM mode is extremely confined in the accumulation layers of TCO with high absorption loss, leading to a great reduction in length for the present polarizer. Moreover, the top TCO layer is applied to further enhance the polarizer performance. Results show that a polarizer of only 4.5 MUm in length with an extinction ratio (ER) of 25.26 dB and an insertion loss of 0.21 dB is achieved at 1.55 MUm, and its bandwidth can be extended to ~140 nm for an ER>20 dB. In addition, the ER can also be increased only by enlarging the length of the TCO-based polarizer. PMID- 27410814 TI - Vector light shift averaging in paraffin-coated alkali vapor cells. AB - Light shifts are an important source of noise and systematics in optically pumped magnetometers. We demonstrate that the long spin-coherence time in paraffin coated cells leads to spatial averaging of the vector light shift over the entire cell volume. This renders the averaged vector light shift independent, under certain approximations, of the light-intensity distribution within the sensor cell. Importantly, the demonstrated averaging mechanism can be extended to other spatially varying phenomena in anti-relaxation-coated cells with long coherence times. PMID- 27410815 TI - Optimal densities of alkali metal atoms in an optically pumped K-Rb hybrid atomic magnetometer considering the spatial distribution of spin polarization. AB - An optically pumped K-Rb hybrid atomic magnetometer can be a useful tool for biomagnetic measurements due to the high spatial homogeneity of its sensor property inside a cell. However, because the property varies depending on the densities of potassium and rubidium atoms, optimization of the densities is essential. In this study, by using the Bloch equations of K and Rb and considering the spatial distribution of the spin polarization, we confirmed that the calculation results of spin polarization behavior are in good agreement with the experimental data. Using our model, we calculated the spatial distribution of the spin polarization and found that the optimal density of K atoms is 3 * 1019 m-3 and the optimal density ratio is nK/nRb ~ 400 to maximize the output signal and enhance spatial homogeneity of the sensor property. PMID- 27410816 TI - Four-channel optically pumped atomic magnetometer for magnetoencephalography. AB - We have developed a four-channel optically pumped atomic magnetometer for magnetoencephalography (MEG) that incorporates a passive diffractive optical element (DOE). The DOE allows us to achieve a long, 18-mm gradiometer baseline in a compact footprint on the head. Using gradiometry, the sensitivities of the channels are < 5 fT/Hz1/2, and the 3-dB bandwidths are approximately 90 Hz, which are both sufficient to perform MEG. Additionally, the channels are highly uniform, which offers the possibility of employing standard MEG post processing techniques. This module will serve as a building block of an array for magnetic source localization. PMID- 27410817 TI - Fourier analysis of RGB fringe-projection profilometry and robust phase demodulation methods against crosstalk distortion. AB - In this paper, we apply the frequency transfer function formalism to analyze the red, green and blue (RGB) phase-shifting fringe-projection profilometry technique. The phase-shifted patterns in RGB fringe projection are typically corrupted by crosstalk because the sensitivity curves of most projection recording systems overlap. This crosstalk distortion needs to be compensated in order to obtain high quality measurements. We study phase-demodulation methods for null/mild, moderate, and severe levels of RGB crosstalk. For null/mild crosstalk distortion, we can estimate the searched phase-map using Bruning's 3 step phase-shifting algorithm (PSA). For moderate crosstalk, the recorded data is usually preprocessed before feeding it into the PSA; alternatively, in this paper we propose a computationally more efficient approach, which combines linear crosstalk compensation with the phase-demodulation algorithm. For severe RGB crosstalk, we expect non-sinusoidal fringes' profiles (distorting harmonics) and a significant uncertainty on the linear crosstalk calibration (which produces pseudo-detuning error). Analyzing these distorting phenomena, we conclude that squeezing interferometry is the most robust demodulation method for RGB fringe projection techniques. Finally, we support our conclusions with numerical simulations and experimental results. PMID- 27410818 TI - Construction of high-dimensional universal quantum logic gates using a Lambda system coupled with a whispering-gallery-mode microresonator. AB - High-dimensional quantum system provides a higher capacity of quantum channel, which exhibits potential applications in quantum information processing. However, high-dimensional universal quantum logic gates is difficult to achieve directly with only high-dimensional interaction between two quantum systems and requires a large number of two-dimensional gates to build even a small high-dimensional quantum circuits. In this paper, we propose a scheme to implement a general controlled-flip (CF) gate where the high-dimensional single photon serve as the target qudit and stationary qubits work as the control logic qudit, by employing a three-level Lambda-type system coupled with a whispering-gallery-mode microresonator. In our scheme, the required number of interaction times between the photon and solid state system reduce greatly compared with the traditional method which decomposes the high-dimensional Hilbert space into 2-dimensional quantum space, and it is on a shorter temporal scale for the experimental realization. Moreover, we discuss the performance and feasibility of our hybrid CF gate, concluding that it can be easily extended to a 2n-dimensional case and it is feasible with current technology. PMID- 27410819 TI - Random sources for beams with azimuthally varying polarization properties. AB - We develop analytical model for statistically stationary sources that radiate beam-like far fields with polarization properties separately controllable in both radial and azimuthal variables. In particular, we demonstrate that for a suitable choice of source parameters a vortex-like far-field distribution of the degree of polarization (DOP) can be obtained. Furthermore, we report the experimental generation of such sources using an optical setup with Mach-Zehnder interferometer having two independent spatial light modulators in its branches. The experimental results agree well with the theoretical predictions. The new class of sources may find uses in imaging, communication and sensing applications based on source polarization diversity. PMID- 27410820 TI - Deconvolution approach for 3D scanning microscopy with helical phase engineering. AB - RESCH (refocusing after scanning using helical phase engineering) microscopy is a scanning technique using engineered point spread functions which provides volumetric information. We present a strategy for processing the collected raw data with a multi-view maximum likelihood deconvolution algorithm, which inherently comprises the resolution gain of pixel-reassignment microscopy. The method, which we term MD-RESCH (for multi-view deconvolved RESCH), achieves in our current implementation a 20% resolution advantage along all three axes compared to RESCH and confocal microscopy. Along the axial direction, the resolution is comparable to that of image scanning microscopy. However, because the method inherently reconstructs a volume from a single 2D scan, a significantly higher optical sectioning becomes directly visible to the user, which would otherwise require collecting multiple 2D scans taken at a series of axial positions. Further, we introduce the use of a single-helical detection PSF to obtain an increased post-acquisition refocusing range. We present data from numerical simulations as well as experiments to confirm the validity of our approach. PMID- 27410821 TI - Role of heat accumulation in the multi-shot damage of silicon irradiated with femtosecond XUV pulses at a 1 MHz repetition rate. AB - The role played by heat accumulation in multi-shot damage of silicon was studied. Bulk silicon samples were exposed to intense XUV monochromatic radiation of a 13.5 nm wavelength in a series of 400 femtosecond pulses, repeated with a 1 MHz rate (pulse trains) at the FLASH facility in Hamburg. The observed surface morphological and structural modifications are formed as a result of sample surface melting. Modifications are threshold dependent on the mean fluence of the incident pulse train, with all threshold values in the range of approximately 36 40 mJ/cm2. Experimental data is supported by a theoretical model described by the heat diffusion equation. The threshold for reaching the melting temperature (45 mJ/cm2) and liquid state (54 mJ/cm2), estimated from this model, is in accordance with experimental values within measurement error. The model indicates a significant role of heat accumulation in surface modification processes. PMID- 27410822 TI - Optical textures: characterizing spatiotemporal chaos. AB - Macroscopic systems subjected to injection and dissipation of energy can exhibit complex spatiotemporal behaviors as result of dissipative self-organization. Here, we report a one- and two-dimensional pattern forming setup, which exhibits a transition from stationary patterns to spatiotemporal chaotic textures, based on a nematic liquid crystal layer with spatially modulated input beam and optical feedback. Using an adequate projection of spatiotemporal diagrams, we determine the largest Lyapunov exponent. Jointly, this exponent and Fourier transform allow us to distinguish between spatiotemporal chaos and amplitude turbulence concepts, which are usually merged. PMID- 27410823 TI - Faraday rotator based on TSAG crystal with <001> orientation. AB - A Faraday isolator (FI) for high-power lasers with kilowatt-level average power and 1-um wavelength was demonstrated using a terbium scandium aluminum garnet (TSAG) with its crystal axis aligned in the <001> direction. Furthermore, no compensation scheme for thermally induced depolarization in a magnetic field was used. An isolation ratio of 35.4 dB (depolarization ratio gamma of 2.9 * 10 4) was experimentally observed at a maximum laser power of 1470 W. This result for room-temperature FIs is the best reported, and provides a simple, practical solution for achieving optical isolation in high-power laser systems. PMID- 27410824 TI - Coherent control of group index and magneto-optical anisotropy in a multilevel atomic vapor. AB - We study electromagnetically induced transparency (EIT) in a heated potassium vapor cell, using a simple optical setup with a single free-running diode laser and an acousto-optic modulator. Despite the fact that the Doppler width is comparable to the ground state hyperfine splitting, transparency windows with deeply sub-natural line widths and large group indices are obtained. A longitudinal magnetic field is used to split the EIT feature and induce magneto optical anisotropy. Using the beat note between co-propagating coupling and probe beams, we perform a heterodyne measurement of the circular dichroism (and therefore birefringence) of the EIT medium. The observed spectra reveal that lin||lin polarizations lead to greater anisotropy than lin?lin. A simplified ||analytical model encompassing sixteen Zeeman states and eighteen Lambda subsytems reproduces the experimental observations. PMID- 27410825 TI - In-focus wavefront sensing using non-redundant mask-induced pupil diversity. AB - Wavefront estimation using in-focus image data is critical to many applications. This data is invariant to a sign flip with complex conjugation of the complex amplitude in the pupil, making for a non-unique solution. Information from an in focus image taken through a non-redundant pupil mask (NRM) can break this ambiguity, enabling the true aberration to be determined. We demonstrate this by priming a full pupil Gerchberg-Saxton phase retrieval with NRM fringe phase information. We apply our method to measure simulated aberrations on the segmented James Webb space telescope (JWST) mirror using full pupil and NRM data from its near infrared imager and slitless spectrograph (NIRISS). PMID- 27410826 TI - Growth of single-crystal YAG fiber optics. AB - Single-crystal YAG (Y3Al5O12) fibers have been grown by the laser heated pedestal growth technique with losses as low as 0.3 dB/m at 1.06 MUm. These YAG fibers are as long as about 60 cm with diameters around 330 MUm. The early fibers were grown from unoriented YAG seed fibers and these fibers exhibited facet steps or ridges on the surface of the fiber. However, recently we have grown fibers using an oriented seed to grow step-free fibers. Scattering losses made on the fibers indicate that the scattering losses are equal to about 30% of the total loss. PMID- 27410827 TI - Fluorescent taggants with temporally coded signatures. AB - In this paper, resonance energy transfer (RET) networks between chromophores are used to implement fluorescent taggants with temporally coded signatures. Because the temporal signature of such a fluorescent taggant is a phase-type distribution defined by the geometry of its RET network, the taggant design is not constrained by resolvable dyes and has a significantly larger coding capacity than spectrally or lifetime coded fluorescent taggants. Meanwhile, the detection process becomes highly efficient when the signatures are coded in the time domain. The taggant identification method is based on the multinomial distribution of detected photons and Maximum Likelihood Estimation, which guarantees high accuracy even with only a few hundred photons and also applies to a mixture of taggants in multiplex detection. Therefore, these temporally coded fluorescent taggants have great potential for both in situ and Lidar applications. PMID- 27410828 TI - Low threshold continuous-wave lasing of yellow-green InGaN-QD vertical-cavity surface-emitting lasers. AB - Low threshold continuous-wave (CW) lasing of current injected InGaN quantum dot (QD) vertical-cavity surface-emitting lasers (VCSELs) was achieved at room temperature. The VCSEL was fabricated by metal bonding technique on a copper substrate to improve the heat dissipation ability of the device. For the first time, lasing was obtained at yellow-green wavelength of 560.4 nm with a low threshold of 0.61 mA, corresponding to a current density of 0.78 kA/cm2. A high degree of polarization of 94% were measured. Despite the operation in the range of "green gap" of GaN-based devices, single longitudinal mode laser emission was clearly achieved due to the high quality of active region based on InGaN QDs and the excellent thermal design of the VCSELs. PMID- 27410829 TI - Mode-locked laser autocollimator with an expanded measurement range. AB - A mode-locked laser is employed as the light source of a laser autocollimator, instead of the conventionally employed single-wavelength laser, for an expanded range of tilt angle measurement. A group of the spatially separated diffracted beams from a diffraction grating are focused by a collimator objective to form an array of light spots on the focal plane of the collimator objective where a light position-sensing photodiode is located for detecting the linear displacement of the light spot array corresponding to the tilt angle of the reflector. A prototype mode-locked femtosecond laser autocollimator is designed and constructed for achieving a measurement range of 11000 arc-seconds. PMID- 27410830 TI - Distributed user-centric scheduling for visible light communication networks. AB - Visible light communication (VLC) networks, consisting of multiple light-emitting diodes (LEDs) acting as optical access points (APs), can provide low-cost high rate data transmission to multiple users simultaneously in indoor environments. However, the performance of VLC networks is severely limited by the interference between different users. In this paper, we establish a distributed user-centric scheduling framework based on stable marriage theory, and propose a novel decentralized scheduling method to manage interference by forming flexible amorphous cells for all users. The proposed scheduling method has provable low computational complexity and requires only the exchange of a few 1-bit messages between the APs and the users but not the feedback of the channel state information of the entire network. We further show that the proposed method can achieve both user-wise and system-wise optimality as well as a certain level of fairness. Simulation results indicate that our decentralized user-centric scheduling method outperforms existing centralized approaches in terms of throughput, fairness, and computational complexity. PMID- 27410831 TI - 110 GHz CMOS compatible thin film LiNbO3 modulator on silicon. AB - In this paper we address a significant limitation of silicon as an optical material, namely, the upper bound of its potential modulation frequency. This arises due to finite carrier mobility, which fundamentally limits the frequency response of all-silicon modulators to about 60 GHz. To overcome this limitation, another material must be integrated with silicon to provide increased operational bandwidths. Accordingly, this paper proposes and demonstrates the integration of a thin LiNbO3 device layer with silicon and a novel tuning process that matches the propagation velocities between the propagating radio-frequency (RF) and optical waves. The resulting lithium niobate on silicon (LiNOS) modulator is demonstrated to operate from DC to 110 GHz. PMID- 27410832 TI - ~1 mJ pulsed vortex laser at 1645 nm with well-defined helicity. AB - We report on a millijoule level Er:YAG ceramic pulsed vortex laser resonantly pumped by an annular beam at 1532 nm. By means of an uncoated YAG crystal plate inserting into the cavity and a proper thermal gradient on the ceramic, 1.03 mJ LG0,-1 mode and 0.97 mJ LG0, + 1 mode were respectively produced, and no vortex mode instability problem was observed. We believe the directly generated millijoule level optical vortex with well-defined helicity will have potential applications in material modification and processing, high field laser physics, and nonlinear optics, etc. PMID- 27410833 TI - Confined migration of induced hot electrons in Ag/graphene/TiO2 composite nanorods for plasmonic photocatalytic reaction. AB - Confined migration of hot electrons is presented in nanorods of layered Ag/graphene/TiO2 structure for highly efficient plasmonic photocatalytic water treatment. The light-illuminating titanium dioxide (TiO2) nanorods provide a large amount of high-energy hot electrons for the generation of highly-active superoxide radical (*O2 ) that leads to the degradation of organics in water. Comparison between photocatalytic processing efficiency by photocatalysts with various composite materials were presented based on the preferred propagation path of induced hot electrons that leads to generation of *O2 -. The best results done by Ag/graphene/TiO2 nanorods showed that the sandwiched layer of graphene on TiO2 nanorods collects the induced hot electrons and results in high efficiency photocatalytic reaction. PMID- 27410834 TI - Local orientation coherence based segmentation and boundary-aware diffusion for discontinuous fringe patterns. AB - Fringe patterns with noise and discontinuity are often encountered but difficult to analyze. Discontinuity-detectable and boundary-aware processing techniques are demanded. A local orientation coherence based fringe segmentation (LOCS) method and its cooperation with boundary-aware coherence enhancing diffusion (BCED) for discontinuous fringe pattern denoising are proposed in this paper. The LOCS method has three steps. First, as orientation coherence indicated by structure tensors is informative to describe fringe structures, it is selected for discontinuity recognition. Due to the complexity of the discontinuity problem, the detected boundary often has missing parts and is not very accurate. Boundary completion by cubic splines and boundary refinement based on partial structure tensors are further performed as the second and third steps, respectively. Subsequently, the BCED method is developed to adapt the original CED to fringe segments with irregular boundaries. Simulated and experimental fringe patterns are tested and successful results have been obtained. PMID- 27410835 TI - Structure and stress studies of low temperature annealed W/Si multilayers for the X-ray telescope. AB - Low stress W/Si multilayer mirrors are demanded in the hard X-ray telescopes to achieve the high angular resolution. To reduce the stress of the as-deposited multilayer and maintain a high reflectivity, two groups of low-temperature annealing experiments were performed on the periodic multilayers with a d-spacing of ~3.8 nm. The temperature-dependent experiments show that the 150 degrees C annealing can slightly increase the reflectivity while the stress reduced only by 24%. Higher temperature annealing induced a larger reduction of the stress and the multilayer reached an almost zero stress state at 250 degrees C. The stress relaxation was accompanied by a small drop of reflectivity of <=5% and a period compaction of <0.02 nm. The time-dependent experiments indicate that most of the stress changes occurred within the first 10 minutes while a prolonged annealing is not useful. The X-ray scattering and transmission electron microscopy were further used to study the microstructure changes of the multilayers. It is found that the W/Si multilayer exhibits an amorphous structure before and after annealing, while an enhanced diffusion and intermixing is the main reason for the stress relaxation and structure changes. PMID- 27410836 TI - Topologically robust transport of entangled photons in a 2D photonic system. AB - We theoretically study the transport of time-bin entangled photon pairs in a two dimensional topological photonic system of coupled ring resonators. This system implements the integer quantum Hall model using a synthetic gauge field and exhibits topologically robust edge states. We show that the transport through edge states preserves temporal correlations of entangled photons whereas bulk transport does not preserve these correlations and can lead to significant unwanted temporal bunching or anti-bunching of photons. We study the effect of disorder on the quantum transport properties; while the edge transport remains robust, bulk transport is very susceptible, and in the limit of strong disorder, bulk states become localized. We show that this localization is manifested as an enhanced bunching/anti-bunching of photons. This topologically robust transport of correlations through edge states could enable robust on-chip quantum communication channels and delay lines for information encoded in temporal correlations of photons. PMID- 27410837 TI - Modulation format identification aided hitless flexible coherent transceiver. AB - We propose a hitless flexible coherent transceiver enabled by a novel modulation format identification (MFI) scheme for dynamic agile optical networks. The modulation format transparent digital signal processing (DSP) is realized by a block-wise decision-directed least-mean-square (DD-LMS) equalizer for channel tracking, and a pilot symbol aided superscalar phase locked loop (PLL) for carrier phase estimation (CPE). For the MFI, the modulation format information is encoded onto the pilot symbols initially used for CPE. Therefore, the proposed MFI method does not require extra overhead. Moreover, it can identify arbitrary modulation formats including multi-dimensional formats, and it enables tracking of the format change for short data blocks. The performance of the proposed hitless flexible coherent transceiver is successfully evaluated with five modulation formats including QPSK, 16QAM, 64QAM, Hybrid QPSK/8QAM and set partitioning (SP)-512-QAM. We show that the proposed MFI method induces a negligible performance penalty. Moreover, we experimentally demonstrate that such a hitless transceiver can adapt to fast block-by-block modulation format switching. Finally, the performance improvement of the proposed MFI method is experimentally verified with respect to other commonly used MFI methods. PMID- 27410838 TI - Multiple beam interference lithography: A tool for rapid fabrication of plasmonic arrays of arbitrary shaped nanomotifs. AB - A novel method enabling rapid fabrication of 2D periodic arrays of plasmonic nanoparticles across large areas is presented. This method is based on the interference of multiple coherent beams originating from diffraction of large diameter collimated beam on a transmission phase mask. Mutual orientation of the interfering beams is determined by parameters of the used phase mask. Herein, parameters of the phase mask (periods and modulation depth) are selected to yield an interference pattern with high contrast and narrow well-separated maxima. Finally, multiple beam interference lithography (MBIL)-based fabrication of periodic plasmonic arrays with selected nanomotifs including discs, disc dimers, rods and bowtie antennas is demonstrated. PMID- 27410839 TI - Nonlinear Raman-Nath second harmonic generation with structured fundamental wave. AB - We proposed and experimentally demonstrated that nonlinear Raman-Nath second harmonic can be achieved in real time when a fundamental wave with the phase periodically modulated, termed as structured fundamental wave, incident in a homogeneous nonlinear medium. The diffraction of second harmonic originates from the structured fundamental wave, rather than the grating of a nonlinear photonic crystal. Nonlinear second harmonic generation, in forms of both one- and two dimensional, was investigated in our experiment. This method circumvents the limitation of nonlinear photonic crystals in some extend and has potential applications in nonlinear frequency conversion, optical signal processing and beam shaping, etc. PMID- 27410840 TI - Sub-wavelength grating for enhanced ring resonator biosensor. AB - While silicon photonic resonant cavities have been widely investigated for biosensing applications, enhancing their sensitivity and detection limit continues to be an area of active research. Here, we describe how to engineer the effective refractive index and mode profile of a silicon-on-insulator (SOI) waveguide using sub-wavelength gratings (SWG) and report on its observed performance as a biosensor. We designed a 30 MUm diameter SWG ring resonator and fabricated it using Ebeam lithography. Its characterization resulted in a quality factor, Q, of 7 . 103, bulk sensitivity Sb = 490 nm/RIU, and system limit of detection sLoD = 2 . 10-6 RIU. Finally we employ a model biological sandwich assay to demonstrate its utility for biosensing applications. PMID- 27410841 TI - Squeezed hollow-core photonic Bragg fiber for surface sensing applications. AB - We propose to use squeezed hollow-core photonic bandgap Bragg fibers for surface sensing applications. We demonstrate theoretically and confirm experimentally that squeezing a section of the Bragg fiber core increases overlap between the optical fields of the core guided modes and the modes bound to the sensing layer, thus, significantly enhancing their interaction via anticrossing phenomenon, which, in turn, enhances surface sensitivity of the fiber sensor. As a practical demonstration, we apply our fiber sensor to in situ monitoring of the dissolution dynamics of a sub-micron-thick polyvinyl butyral (PVB) film coated on the surface of the liquid-filled Bragg fiber core. Strong spectral shift is observed during the dissolution of the PVB film, and a surface spectral sensitivity of ~0.07nm/nm is achieved experimentally with aqueous analytes. The proposed fiber sensor offers a new sensing modality and opens new sensing applications for photonic bandgap fibers, such as real-time detection of binding and affinity, study of kinetics, etc. for a range of chemical and biological samples. PMID- 27410842 TI - Tailored loss discrimination in indefinite metamaterial-clad hollow-core fibers. AB - We analyze the modal attenuation properties of silica hollow-core fibers with a gold-wire based indefinite metamaterial cladding at 10.6 um. We find that by varying the metamaterial feature sizes and core diameter, the loss discrimination can be tailored such that either the HE11, TE01 or TM01 mode has the lowest loss, which is particularly difficult to achieve for the radially polarized mode in commonly used hollow-core fibers. Furthermore, it is possible to tailor the HE11 and TM01 modes in the metamaterial-clad waveguide so that they possess attenuations lower than in hollow tubes composed of the individual constituent materials. We show that S-parameter retrieval techniques in combination with an anisotropic dispersion equation can be used to predict the loss discrimination properties of such fibers. These results pave the way for the design of metamaterial hollow core fibers with novel guidance properties, in particular for applications demanding cylindrically polarized modes. PMID- 27410843 TI - Attenuation and diffusion produced by small-radius curvatures in POFs. AB - Our aim is to characterize curvatures using a methodology previously applied to other localized disturbances in plastic optical fibers (POFs). The effects of several curvature radii and turn angles have been analyzed, so that for each condition, angular dependent attenuation and diffusion are obtained from experimental measurements to construct a matrix that accounts for the global effects of power loss and mode mixing introduced by the curvature over the angular power distribution. Power loss as a function of bend radius was calculated using the characteristic matrices and compared to experimental results to validate the model. This curvature model can be a useful tool to predict the impact of bends on transmission properties as is demonstrated in the example of a small network in a domestic environment. PMID- 27410844 TI - Isolator-free switchable uni- and bidirectional hybrid mode-locked erbium-doped fiber laser. AB - An Erbium-doped fibre ring laser hybrid mode-locked with single-wall carbon nanotubes (SWNT) and nonlinear polarisation evolution (NPE) without an optical isolator has been investigated for various cavity conditions. Precise control of the state of polarisation (SOP) in the cavity ensures different losses for counter-propagating optical fields. As the result, the laser operates in quasi unidirectional regime in both clockwise (CW) and counter-clockwise (CCW) directions with the emission strengths difference of the directions of 22 dB. Furthermore, by adjusting the net birefringence in the cavity, the laser can operate in a bidirectional generation. In this case, a laser pumped with 75 mW power at 980 nm generates almost identical 790 and 570 fs soliton pulses with an average power of 1.17 and 1.11 mW. The operation stability and pulse quality of the soliton pulses in both unidirectional regimes are highly competitive with those generated in conventional ring fibre lasers with isolator in the cavity. Demonstrated bidirectional laser operation can find vital applications in gyroscopes or precision rotation sensing technologies. PMID- 27410845 TI - Broadband extraordinary terahertz transmission through super-aligned carbon nanotubes film. AB - We experimentally demonstrate the extraordinary transmission of THz waves through super-aligned multi-walled carbon nanotube (MWCNT) films with one-dimensional arrays of sub-wavelength rectangular gratings in the broad frequency range from 0.2 to 2.5 THz. To achieve this, two kinds of MWCNT films (1 MUm and 3 MUm in thickness) were fabricated by drawing from a sidewall of super-aligned nanotube arrays synthesized by low pressure chemical vapor deposition. The measured complex refraction index of the film exhibits highly anisotropic transmission of THz waves through the MWCNTs. The anisotropy depends not only on the polarization direction of the THz waves but also on the orientation of the MWCNT gratings. We found that the resonantly extraordinary THz transmission originated from the surface plasmon polaritons supported by periodically patterned carbon nanotube gratings. Our experimental results may provide important insights for emerging THz plasmonic devices based on carbon nanotubes. PMID- 27410846 TI - Adaptive, spatially-varying aberration correction for real-time holographic projectors. AB - A method of generating an aberration- and distortion-free wide-angle holographically projected image in real time is presented. The target projector is first calibrated using an automated adaptive-optical mechanism. The calibration parameters are then fed into the hologram generation program, which applies a novel piece-wise aberration correction algorithm. The method is found to offer hologram generation times up to three orders of magnitude faster than the standard method. A projection of an aberration- and distortion-free image with a field of view of 90x45 degrees is demonstrated. The implementation on a mid-range GPU achieves high resolution at a frame rate up to 12fps. The presented methods are automated and can be performed on any holographic projector. PMID- 27410848 TI - Sampling criteria for Fourier ptychographic microscopy in object space and frequency space. AB - Fourier ptychographic microscopy (FPM) is a new computational super-resolution approach, which can obtain not only the correct object function, but also the pupil aberration, the LED misalignment, and beyond. Although many state-mixed FPM techniques have been proposed to achieve higher data acquisition efficiency and recovery accuracy in the past few years, little is known that their reconstruction performance highly depends on the data redundancy in both object and frequency domains. Generally, at least 35% aperture overlapping percentage in the Fourier domain is needed for a successful reconstruction using ordinary FPM method. However, the data redundancy requirements for those state-mixed FPM schemes are largely remained unexplored until now. In this paper, we explore the spatial and spectrum data redundancy requirements for the FPM recovery process to introduce sampling criteria for the conventional and state-mixed FPM techniques in both object and frequency space. Moreover, an upsampled FPM method is proposed to solve the pixel aliasing problem, and an alternative illumination-angle subsampled FPM scheme is introduced to get rid of the complexity of decoherence and achieve the expected recovery quality with reduced data quantity. All the proposed methods and sampling criteria are validated with both simulations and experiments, and our results show that state-mixed techniques cannot provide a significant performance advantage since they are much more sensitive to data redundancy. This paper provides both the guidelines for designing the most suitable FPM platform and the insights for the capabilities and limitations of the FPM approach. PMID- 27410847 TI - Time-resolved luminescence imaging of intracellular oxygen levels based on long lived phosphorescent iridium(III) complex. AB - Time-resolved luminescence imaging of intracellular oxygen levels has been demonstrated based on long-lived phosphorescent signal. A phosphorescent dinuclear iridium(III) complex Ir1 has been designed and synthesized, which exhibits excellent optical properties, such as high quantum yields, large Stokes shift, high photostability and long emission lifetime. The phosphorescent intensity and lifetime of complex are very sensitive to oxygen levels. Thus, the application of Ir1 for monitoring intracellular oxygen levels has been realized successfully. Especially, utilizing the advantageous long emission lifetime of Ir1, the background fluorescence interference could be eliminated effectively by using the photoluminescence lifetime imaging and time-gated luminescence imaging techniques, improving the signal-to-noise ratios in bioimaging. PMID- 27410849 TI - Full monitoring for long-reach TWDM passive optical networks. AB - This paper presents a novel and simple fiber monitoring system based on multi wavelength transmission-reflection analysis for long-reach time and wavelength division multiplexing passive optical networks. For the first time, the full localization functionality of long-reach passive optical networks is possible with the proposed monitoring scheme, including supporting fault detection, identification, and localization in both feeder and distribution fiber segments. By measuring the transmitted and reflected/backscattered optical powers launched by an unmodulated continuous-wave optical source, the proposed solution is able to supervise the network with good spatial accuracy, a high detection speed and a low impact on data traffic. Both the theoretical analysis and experimental validation show that the proposed scheme is capable of providing an accurate fault monitoring functionality for long-reach time and wavelength division multiplexing passive optical networks. PMID- 27410850 TI - Modal content in hypocycloid Kagome hollow core photonic crystal fibers. AB - The modal content of 7 and 19 cell Kagome anti resonant hollow core fibers (K ARF) with hypocycloid core surrounds is experimentally investigated through the spectral and spatial (S2) imaging technique. It is observed that the 7 and 19 cell K-ARF reported here, support 4 and 7 LP mode groups respectively, however the observation that K-ARF support few mode groups is likely to be ubiquitous to 7 and 19 cell K-ARFs. The transmission loss of the higher order modes (HOMs) was measured via S2 and a cutback method. In the 7 cell K ARF it is found that the LP11 and LP21 modes have approximately 3.6 and 5.7 times the loss of the fundamental mode (FM), respectively. In the 19 cell it is found that the LP11 mode has approximately 2.57 times the loss of the FM, while the LP02 mode has approximately 2.62 times the loss of the FM. Additionally, bend loss in these fibers is studied for the first time using S2 to reveal the effect of bend on modal content. Our measurements demonstrate that K-ARFs support a few mode groups and indicate that the differential loss of the HOMs is not substantially higher than that of the FM, and that bending the fiber does not induce significant inter modal coupling. A study of three different input beam coupling configurations demonstrates increased HOM excitation at output and a non Gaussian profile of the output beam if poor mode field matching is achieved. PMID- 27410851 TI - Electromagnetic biaxial vector scanner using radial magnetic field. AB - We present an electromagnetic biaxial vector-graphic scanning micromirror. In contrast to conventional electromagnetic actuators using linear magnetic field, proposed device utilizes a radial magnetic field and uniquely designed current paths to enable the 2 degree-of-freedom scanning motion. As the radial field is generated by concentrically assembled magnets placed under the scanner die, large driving torque can be generated without the aid of hermetic packaging and relatively small device volume can be achieved. Mechanical half scan angle of 6.43 degrees and 4.20 degrees have been achieved at DC current of 250mA and 350mA for horizontal and vertical scans, respectively. Forced actuation along both scan axes has been realized by feedback control. PMID- 27410852 TI - Brownian motion properties of optoelectronic random bit generators based on laser chaos. AB - The nondeterministic property of the optoelectronic random bit generator (RBG) based on laser chaos are experimentally analyzed from two aspects of the central limit theorem and law of iterated logarithm. The random bits are extracted from an optical feedback chaotic laser diode using a multi-bit extraction technique in the electrical domain. Our experimental results demonstrate that the generated random bits have no statistical distance from the Brownian motion, besides that they can pass the state-of-the-art industry-benchmark statistical test suite (NIST SP800-22). All of them give a mathematically provable evidence that the ultrafast random bit generator based on laser chaos can be used as a nondeterministic random bit source. PMID- 27410853 TI - Novel robust skylight compass method based on full-sky polarization imaging under harsh conditions. AB - A novel method based on Pulse Coupled Neural Network(PCNN) algorithm for the highly accurate and robust compass information calculation from the polarized skylight imaging is proposed,which showed good accuracy and reliability especially under cloudy weather,surrounding shielding and moon light. The degree of polarization (DOP) combined with the angle of polarization (AOP), calculated from the full sky polarization image, were used for the compass information caculation. Due to the high sensitivity to the environments, DOP was used to judge the destruction of polarized information using the PCNN algorithm. Only areas with high accuracy of AOP were kept after the DOP PCNN filtering, thereby greatly increasing the compass accuracy and robustness. From the experimental results, it was shown that the compass accuracy was 0.1805 degrees under clear weather. This method was also proven to be applicable under conditions of shielding by clouds, trees and buildings, with a compass accuracy better than 1 degrees . With weak polarization information sources, such as moonlight, this method was shown experimentally to have an accuracy of 0.878 degrees . PMID- 27410854 TI - Two-dimensional design and analysis of trench-coupler based Silicon Mach-Zehnder thermo-optic switch. AB - Optical switches are key components for routing of light transmission paths in data links. Existing waveguide-based Mach-Zehnder interferometer (MZI) switches occupy a significant amount of real estate on-chip. Here we propose a compact Silicon MZI thermo-optic 2 * 2 photonic switch, consisting of two frustrated total internal reflection (TIR) trench couplers and TIR mirror-based 90 degrees waveguide bends, forming a rectangular MZI configuration. The switch allows for reconfigurable design footprints due to selected control of the optical signal being transmitted and reflected at the 90 degrees crosses and bends. Our analysis results show that the switch exhibits a chip size of 42 um * 42 um, the extinction ratio of ~14 dB, the rise and fall time of 20 MUs and 16 MUs, and the low switching voltage and power of 0.35 V and 26 mW, respectively. This device configuration can readily scale its pattern at the two-dimensional directions, making them attractive for Silicon photonic integrated circuits. PMID- 27410855 TI - Measuring parallelism of two parallel narrow beams based on differential defocusing principle. AB - We present a method of measuring the parallelism of two parallel narrow beams by positioning a CCD each before and after the focal plane of the collimation lens. Because of this differential defocused positioning of the two CCDs, the two beam spots cannot overlap on the CCD image plane even if they are nearly parallel, and the distance between the two spots on each CCD can be obtained simultaneously, which eliminates the influence of environmental noise. Our experimental results show that a satisfactory system stability and resolution of 0.1" and 0.2", respectively, can be obtained with the proposed method. PMID- 27410856 TI - Flexible optical manipulation of ring resonator by frequency detuning and double port excitation. AB - Optical force exerted on a ring resonator, which can move freely in plane, is investigated using the finite-difference in time-domain method. In order to manipulate the ring resonator more flexibly, two assistant waveguides are introduced to form a microring resonator based add-drop device. Results show that a blue tuned source is more suitable for the manipulation of the ring, rather than the central resonant frequency as expected. A red-tuned frequency, however, is difficult to trap the ring stably. When the frequency detuning is combined with selected double-port excitation, the ring can be trapped stably at some discrete positions, some determined regions, or be transported continuously along the waveguide. This optically reconfigurable opto-mechanical resonant system may find potential applications in tunable photonic devices and precise sensing. PMID- 27410858 TI - Excitation of surface waves on the interfaces of general bi-isotropic media. AB - We study theoretically the characteristics of surface waves excited at the interface between a metal and a general bi-isotropic medium, which includes isotropic chiral media and Tellegen media as special cases. We derive an analytical dispersion relation for surface waves, using which we calculate the effective index and the propagation length numerically. We also calculate the absorptance, the cross-polarized reflectance and the spatial distribution of the electromagnetic fields for plane waves incident on a bilayer system consisting of a metal layer and a bi-isotropic layer in the Kretschmann configuration, using the invariant imbedding method. The results obtained using the invariant imbedding method agree with those obtained from the dispersion relation perfectly. In the case of chiral media, the effective index is an increasing function of the chirality index, whereas in Tellegen media, it is a decreasing function of the Tellegen parameter. The propagation length for surface waves in both cases increase substantially as either the chirality index or the Tellegen parameter increases. In Tellegen media, it diverges to infinity when the effective index goes to zero, whereas in chiral media, it does when the parameters approach the cutoff values where quasi surface waves are excited. We investigate the characteristics of quasi surface waves excited when the chirality index is sufficiently large. PMID- 27410857 TI - Highly sensitive gas leak detector based on a quartz-enhanced photoacoustic SF6 sensor. AB - The implementation, performance validation, and testing of a gas-leak optical sensor based on mid-IR quartz-enhanced photoacoustic (QEPAS) spectroscopic technique is reported. A QEPAS sensor was integrated in a vacuum-sealed test station for mechatronic components. The laser source for the sensor is a quantum cascade laser emitting at 10.56 um, resonant with a strong absorption band of sulfur hexafluoride (SF6), which was selected as a leak tracer. The minimum detectable concentration of the QEPAS sensor is 2.7 parts per billion with an integration time of 1 s, corresponding to a sensitivity of leak flows in the 10-9 mbar?l/s range, comparable with state-of-the-art leak detection techniques. PMID- 27410859 TI - Simultaneous algebraic reconstruction technique based on guided image filtering. AB - The challenge of computed tomography is to reconstruct high-quality images from few-view projections. Using a prior guidance image, guided image filtering smoothes images while preserving edge features. The prior guidance image can be incorporated into the image reconstruction process to improve image quality. We propose a new simultaneous algebraic reconstruction technique based on guided image filtering. Specifically, the prior guidance image is updated in the image reconstruction process, merging information iteratively. To validate the algorithm practicality and efficiency, experiments were performed with numerical phantom projection data and real projection data. The results demonstrate that the proposed method is effective and efficient for nondestructive testing and rock mechanics. PMID- 27410860 TI - Development and validation of a reconstruction algorithm for three-dimensional nonlinear tomography problems. AB - This work reports the development and experimental validation of a reconstruction algorithm for three-dimensional (3D) nonlinear tomography problems. Many optical tomography problems encountered in practice are nonlinear, for example, due to significant absorption, multiple-scattering, or radiation trapping. Past research efforts have predominately focused on reconstruction algorithms for linear problems, and these algorithms are not readily extendable to nonlinear problems due to several challenges. These challenges include the computational cost caused by the nonlinearity (which was compounded by the large scale of the problems when they are 3D), the limited view angles available in many practical applications, and the measurement uncertainty. A new algorithm was therefore developed to overcome these challenges. The algorithm was validated both numerically and experimentally, and was demonstrated to be able to solve a range of nonlinear tomography problems with significantly enhanced efficiency and accuracy compared to existing algorithms. PMID- 27410861 TI - Predicting visibility of interference fringes in X-ray grating interferometry. AB - The interference fringe visibility is a common figure of merit in designs of x ray grating-based interferometers. Presently one has to resort to laborious computer simulations to predict fringe visibility values of interferometers with polychromatic x-ray sources. Expanding the authors' previous work on Fourier expansion of the intensity fringe pattern, in this work the authors developed a general quantitative theory to predict the intensity fringe pattern in closed form formulas, which incorporates the effects of partial spatial coherence, spectral average and detector pixel re-binning. These formulas can be used to predict the fringe visibility of a Talbot-Lau interferometer with any geometry configuration and any source spectrum. PMID- 27410862 TI - Frequency-domain nonlinear optics in two-dimensionally patterned quasi-phase matching media. AB - Advances in the amplification and manipulation of ultrashort laser pulses have led to revolutions in several areas. Examples include chirped pulse amplification for generating high peak-power lasers, power-scalable amplification techniques, pulse shaping via modulation of spatially-dispersed laser pulses, and efficient frequency-mixing in quasi-phase-matched nonlinear crystals to access new spectral regions. In this work, we introduce and demonstrate a new platform for nonlinear optics which has the potential to combine these separate functionalities (pulse amplification, frequency transfer, and pulse shaping) into a single monolithic device that is bandwidth- and power-scalable. The approach is based on two dimensional (2D) patterning of quasi-phase-matching (QPM) gratings combined with optical parametric interactions involving spatially dispersed laser pulses. Our proof of principle experiment demonstrates this technique via mid-infrared optical parametric chirped pulse amplification of few-cycle pulses. Additionally, we present a detailed theoretical and numerical analysis of such 2D-QPM devices and how they can be designed. PMID- 27410863 TI - Nematic liquid crystal reorientation around multi-walled carbon nanotubes mapped via Raman microscopy. AB - We have studied the formation of topological defects in liquid crystal (LC) matrices induced by multiwalled carbon nanotubes (MWCNTs) and external electric fields. The defects are ascribable to a distortion of the LC molecular director in proximity of the MWCNT surface. The system is analyzed macroscopically using spectroscopic variable angle ellipsometry. Concurrently, confocal micro-Raman spectroscopy is used to study the system state at the microscale. This allows to acquire a three-dimensional, spatially-resolved map of the topological defect, determining scale length variations and orientation topography of the LC molecules around the MWCNT. PMID- 27410864 TI - Monolithic AlGaAs second-harmonic nanoantennas. AB - We demonstrate monolithic aluminum gallium arsenide (AlGaAs) optical nanoantennas. Using a selective oxidation technique, we fabricated epitaxial semiconductor nanocylinders on an aluminum oxide substrate. Second harmonic generation from AlGaAs nanocylinders of 400 nm height and varying radius pumped with femtosecond pulses delivered at 1554-nm wavelength has been measured, revealing a peak conversion efficiency exceeding 10-5 for nanocylinders with an optimized geometry. PMID- 27410866 TI - All-optical bright gamma-ray and dense positron source by laser driven plasmas filled cone. AB - An all-optical scheme for bright gamma-rays and dense e-e+ pair source is proposed by irradiating a 1022 W/cm2 laser onto a near-critical-density plasmas filled Al cone. Two-dimensional (2D) QED particle-in-cell (PIC) simulations show that, a dense electron bunch is confined in the laser field due to the radiation reaction and the trapped electrons oscillate transversely, emitting bright gamma-rays forward in two ways: (1) nonlinear Compton scattering due to oscillation of electrons in the laser field, and (2) Compton backwardscattering resulting from the bunch colliding with the reflected laser by the cone tip. Finally, the multi-photon Breit-Wheeler process is initiated, producing abundant e-e+ pairs with a density of ~ 1027m-3. The scheme is further demonstrated by full 3D PIC simulations, which indicates a positron number up to 2 * 109. This compact gamma-rays and e-e+ pair source may have many potential applications, such as the laboratory study of astrophysics and nuclear physics. PMID- 27410865 TI - Optical field and attractive force at the subwavelength slit. AB - In recent works, a novel light-induced attractive force was predicted between two metal plates. This force arises by the interaction of surface plasmons which are excited at the metal when a transverse magnetic mode propagates through a subwavelength slit between two metal bodies. In this paper, the analytical and numerical calculations of this magnetic field are presented for the perfect metal and for gold. The amplitude and the phase transient curves between the known limiting cases of narrow and wide slits compared to the wavelength are found. The curve is shown to oscillate due to the emergence of new waveguide modes. The analytic solution for the perfect metal is in agreement with the computation for gold by means of the finite element method. The simple asymptotic formula for the light-induced attractive force is found in the limit of a narrow slit. PMID- 27410867 TI - Electro-optical characteristics of an in-plane-switching liquid crystal cell with zero rubbing angle: dependence on the electrode structure. AB - When an electric field is applied to in-plane switching (IPS) and fringe-field switching (FFS) cells with zero rubbing angle, virtual walls are built such that the switching speed can be increased several-fold. In this study, we investigate the dependence on the interdigitated electrode structure of the electro-optical characteristics of IPS and FFS cells with zero rubbing angle. We found that when the rubbing angle is zero, the single-layered IPS electrode structure provides a higher transmittance than the double-layered FFS electrode structure because of the reduced width of dead zones at domain boundaries between interdigitated electrodes. Single-layered IPS electrodes not only minimize the transmittance decrease but also provide a shorter response time than double-layered FFS electrodes, although the operating voltage is higher and fabrication requires a more precise rubbing process. The transmittance decrease due to the zero rubbing angle in an IPS cell can be minimized using optimization of the electrode structure while retaining a short response time. PMID- 27410868 TI - Airy-type solitary wave in highly noninstantaneous Kerr media. AB - We investigate the dynamics of a decelerating Airy pulse in the highly noninstantaneous Kerr media. It is found that the deceleration of the Airy pulse can be counteracted by the highly noninstantaneous nonlinearity. When the power of the pulse is specifically chosen, the deceleration of the Airy pulse can be totally restrained, and an Airy-type solitary wave is observed within several dispersion lengths. PMID- 27410869 TI - Visualization of Bloch surface waves and directional propagation effects on one dimensional photonic crystal substrate. AB - This paper reports a novel approach to the direct observation of Bloch surface waves, wherein a layer of fluorescent material is deposited directly on the surface of a semi-infinite periodic layered cell. A set of surface nano-gratings is used to couple pumping light to Bloch surface waves, while the sample is rotated until the pumping light meets the quasi-phase matching conditions. This study investigated the directional propagation of waves on stripe and circular one-dimensional grating structures by analyzing the dispersion relationship of the first two eigen modes. Our results demonstrate the efficacy of the proposed scheme in visualizing Bloch surface waves, which could be extended to a variety of other devices. PMID- 27410870 TI - Size and morphology dependent evolution of resonant modes in ZnO microspheres grown by hydrothermal synthesis. AB - We report the correlation between inner morphology, size and whispering gallery mode (WGM) behavior in ZnO microspheres (MSs) grown by hydrothermal method. WGMs in different ZnO microspheres with diameters in the range of 2 - 6 MUm were analyzed by a modified refractive index (MRI) scheme. We found that the size dependence of WGMs in our system is more complicated than others because of the appearance of porosity inside each sphere. Such features might account for the refractive index change and peak shift. Despite that, our MRI scheme can detect such complex features and reproduce universal relations between all important quantities of a microsphere WGM resonator. PMID- 27410871 TI - Optical fiber sensor based on Bloch surface wave in photonic crystals. AB - A new optical fiber sensor based on Bloch surface wave was theoretically proposed. An omnidirectional one-dimensional photonic crystal was designed as the multilayer coated on the outer surface of the optical fiber. Taking advantages of the omnidirectional reflection band, there is only surface mode resonance in the transmission spectrum, while guided mode resonance is avoided. The performance of the designed fiber sensor was analyzed theoretically with a ray transmission model. The presented sensor has comparable sensitivity but much higher figure of merit than other fiber sensors. The resolution can reach about 10-6 RIU or even higher. PMID- 27410872 TI - Efficiency enhancement in a backside illuminated 1.12 MUm pixel CMOS image sensor via parabolic color filters. AB - The shrinkage of pixel size down to sub-2 MUm in high-resolution CMOS image sensors (CISs) results in degraded efficiency and increased crosstalk. The backside illumination technology can increase the efficiency, but the crosstalk still remains an critical issue to improve the image quality of the CIS devices. In this paper, by adopting a parabolic color filter (P-CF), we demonstrate efficiency enhancement without any noticeable change in optical crosstalk of a backside illuminated 1.12 MUm pixel CIS with deep-trench-isolation structure. To identify the observed results, we have investigated the effect of radius of curvature (r) of the P-CF on the efficiency and optical crosstalk of the CIS by performing an electromagnetic analysis. As the r of P-CF becomes equal to (or half) that of the microlens, the efficiencies of the B-, G-, and R-pixels increase by a factor of 14.1% (20.3%), 9.8% (15.3%), and 15.0% (15.7%) with respect to the flat CF cases without any noticeable crosstalk change. Also, as the incident angle increases up to 30 degrees , the angular dependence of the efficiency and crosstalk significantly decreases by utilizing the P-CF in the CIS. Meanwhile, further reduction of r severely increases the optical crosstalk due to the increased diffraction effect, which has been confirmed with the simulated electric-field intensity distribution inside the devices. PMID- 27410873 TI - Wide-field microscopic FRET imaging using simultaneous spectral unmixing of excitation and emission spectra. AB - Simultaneous spectral unmixing of excitation and emission spectra (ExEm unmixing) has the inherent ability to resolve donor emission, fluorescence resonance energy transfer (FRET)-sensitized acceptor emission and directly excited acceptor emission. We here develop an ExEm unmixing-based quantitative FRET measurement method (EES-FRET) independent of excitation intensity and detector parameter setting. The ratio factor (rK), predetermined using a donor-acceptor tandem construct, of total acceptor absorption to total donor absorption in excitation wavelengths used is introduced for determining the concentration ratio of acceptor to donor. We implemented EES-FRET method on a wide-field microscope to image living cells expressing tandem FRET constructs with different donor acceptor stoichiometry. PMID- 27410874 TI - Vertically-oriented nanoparticle dimer based on focused plasmonic trapping. AB - We proposed a vertically-oriented dimer structure based on focused plasmonic trapping of metallic nanoparticle. Quantitative FDTD calculations and qualitative analysis by simplified dipole approximation revealed that localized surface plasmon coupling dominates in the plasmon hybridization, and the vertically oriented dimer can effectively make use of the dominant longitudinal component of the surface plasmon virtual probe thus providing much stronger electric field in the gap. Furthermore, for practical application the top nanoparticle of the dimer can be replaced with an atomic force microscope tip which enables the precise control of the gap distance of the dimer. Therefore the proposed vertically oriented dimer structure provides both the scanning capability and the extremely high electrical field necessary for the high sensitivity Raman imaging. PMID- 27410875 TI - Theoretical optimal modulation frequencies for scattering parameter estimation and ballistic photon filtering in diffusing media. AB - The efficiency of using intensity modulated light for the estimation of scattering properties of a turbid medium and for ballistic photon discrimination is theoretically quantified in this article. Using the diffusion model for modulated photon transport and considering a noisy quadrature demodulation scheme, the minimum-variance bounds on estimation of parameters of interest are analytically derived and analyzed. The existence of a variance-minimizing optimal modulation frequency is shown and its evolution with the properties of the intervening medium is derived and studied. Furthermore, a metric is defined to quantify the efficiency of ballistic photon filtering which may be sought when imaging through turbid media. The analytical derivation of this metric shows that the minimum modulation frequency required to attain significant ballistic discrimination depends only on the reduced scattering coefficient of the medium in a linear fashion for a highly scattering medium. PMID- 27410876 TI - Probing the 3D structure of cornea-like collagen liquid crystals with polarization-resolved SHG microscopy. AB - This work aims at characterizing the three-dimensional organization of liquid crystals composed of collagen, in order to determine the physico-chemical conditions leading to highly organized structures found in biological tissues such as cornea. To that end, we use second-harmonic generation (SHG) microscopy, since aligned collagen structures have been shown to exhibit intrinsic SHG signals. We combine polarization-resolved SHG experiments (P-SHG) with the theoretical derivation of the SHG signal of collagen molecules tilted with respect to the focal plane. Our P-SHG images exhibit striated patterns with variable contrast, as expected from our analytical and numerical calculations for plywood-like nematic structures similar to the ones found in the cornea. This study demonstrates the benefits of P-SHG microscopy for in situ characterization of highly organized biopolymers at micrometer scale, and the unique sensitivity of this nonlinear optical technique to the orientation of collagen molecules. PMID- 27410877 TI - Phase-space approach to lensless measurements of optical field correlations. AB - We analyze and test a general approach for efficiently measuring space-variant partially coherent quasi-monochromatic fields using only amplitude masks and free propagation. A phase-space description is presented to analyze approaches of this type and understand their limitations. Three variants of the method are discussed and compared, the first using an aperture mask, the second employing both an obstacle (the exact inverse of the aperture) and a clear mask, and the last combining the previous two. We discuss the advantages and disadvantages of each option. PMID- 27410878 TI - Design and fabrication of a diffractive beam splitter for dual-wavelength and concurrent irradiation of process points. AB - We report on a dual-wavelength diffractive beam splitter designed for use in parallel laser processing. This novel optical element generates two beam arrays of different wavelengths and allows their overlap at the process points on a workpiece. To design the deep surface-relief profile of a splitter using a simulated annealing algorithm, we introduce a heuristic but practical scheme to determine the maximum depth and the number of quantization levels. The designed corrugations were fabricated in a photoresist by maskless grayscale exposure using a high-resolution spatial light modulator. We characterized the photoresist splitter, thereby validating the proposed beam-splitting concept. PMID- 27410879 TI - Temporal properties of Zernike modes for non-Kolmogorov turbulence. AB - Temporal properties of Zernike modes are investigated for the case of light wave propagation through the non-Kolmogorov turbulence. The calculations are performed for the weak-turbulence conditions with constant turbulence parameters along the propagation path and taking into account the effects of the outer and inner scale of the turbulence. It is shown that the difference between effects produced by the Kolmogorov and non-Kolmogorov turbulence is getting smaller when the aberration order is growing up and when the outer scale magnitude is decreasing. Also it is shown that the correlation time of an aberration is decreasing with increasing of its order and with decreasing of spectral index. PMID- 27410880 TI - Full-vector multi-mode fiber modeling for short reach serdes links of 112Gbps and beyond. AB - A rigorous full-vector multi-mode fiber (MMF) model is proposed. It is believed to be the first comparative study of vector and scalar MMF model in terms of differential mode delay (DMD), mode power distribution (MPD), transfer functions as well as eye diagrams. It shows that the vector nature of fiber modes cannot be ignored even though the refractive index difference can be as small as 1%. A standard-compliant methodology for MMF characterization is introduced. The impact of fiber parameters on bandwidth is studied. The statistical transfer function model of OM3 and OM4 fiber is provided. These transfer functions can be applied to the MMF link modeling. Rigorous full-vector MMF model is an essential tool for research and development of MMF link transceivers and standard development of 112Gbps and beyond. PMID- 27410881 TI - Dual-wavelength passively q-switched single-frequency fiber laser. AB - We propose a compact dual-wavelength Q-switched single-frequency fiber laser based on a 17-mm-long home-made highly Er3+/Yb3+ co-doped phosphate fiber (EYDPF) and a semiconductor saturable absorber mirror (SESAM). The short cavity length and a polarization-maintaining fiber Bragg grating (PM FBG) ensure that only one longitudinal mode is supported by each reflection peak. The maximum pulse energy of more than 34.5 nJ was realized with the shortest pulse duration of 110.5 ns and the Q-switched fiber laser has a repetition rate reaching over 700 kHz with a temporal synchronization of pulses at two wavelengths. Besides, the optical signal-to-noise ratio (OSNR) of larger than 64.5 dB was achieved. PMID- 27410883 TI - Robust hybrid quantum dot laser for integrated silicon photonics. AB - We demonstrate the first quantum dot (QD) laser on a silicon substrate with efficient coupling of light to a silicon waveguide under the QD gain region. Continuous wave operation up to 100 degrees C and multiwavelength operation are demonstrated, paving the way towards highly efficient CMOS-compatible, uncooled, WDM sources. PMID- 27410882 TI - Two-photon luminescence thermometry: towards 3D high-resolution thermal imaging of waveguides. AB - We report on the use of the Erbium-based luminescence thermometry to realize high resolution, three dimensional thermal imaging of optical waveguides. Proof of concept is demonstrated in a 980-nm laser pumped ultrafast laser inscribed waveguide in Er:Yb phosphate glass. Multi-photon microscopy images revealed the existence of well confined intra-waveguide temperature increments as large as 200 degrees C for moderate 980-nm pump powers of 120 mW. Numerical simulations and experimental data reveal that thermal loading can be substantially reduced if pump events are separated more than the characteristic thermal time that for the waveguides investigated is in the ms time scale. PMID- 27410884 TI - All-semiconductor plasmonic gratings for biosensing applications in the mid infrared spectral range. AB - We propose 1D periodic, highly doped InAsSb gratings on GaSb substrates as biosensing platforms applicable for surface plasmon resonance and surface enhanced infrared absorption spectroscopies. Based on finite-difference time domain simulations, the electric field enhancement and the sensitivity on refractive index variations are investigated for different grating geometries. The proposed, optimized system achieves sensitivities of 900 nm RIU-1. A clear red shift of the plasmon resonance as well as the enhancement of an absorption line are presented for 2 nm thin adlayers in simulations. We experimentally confirm the high sensitivity of the InAsSb grating by measurements of the wavelength shift induced by a 200 nm thin polymethylmethacrylate layer and demonstrate an enhancement of vibrational signals. A comparison to a gold grating with equivalent optical properties in the mid-infrared is performed. Our simulations and experimental results underline the interest in the alternative plasmonic material InAsSb for highly sensitive biosensors for the mid-infrared spectral range. PMID- 27410885 TI - Single mode criterion - a benchmark figure to optimize the performance of nonlinear fibers. AB - Optical fibers with sub-wavelength cores are promising systems for efficient nonlinear light generation. Here we reveal that the single-mode criterion represents a convenient design tool to optimize the performance of nonlinear fibers circumventing intense numerical calculations. We introduce a quasi analytic expression for the nonlinear coefficient allowing us to investigate its behavior over a large parameter range. The study is independent of the actual value of the material nonlinearity and shows the fundamental dependencies of the nonlinear coefficient on wavelength, refractive index and core diameter, elucidated by detailed case studies of fused silica and chalcogenide tapers and hybrid fibers. PMID- 27410886 TI - Experimental evidence of dynamical propagation for solitary waves in ultra slow stochastic non-local Kerr medium. AB - We perform a statistical analysis of the optical solitary wave propagation in an ultra-slow stochastic non-local focusing Kerr medium such as liquid crystals. Our experimental results show that the localized beam trajectory presents a dynamical random walk whose beam position versus the propagation distance z depicts two different kind of evolutions A power law is found for the beam position standard deviation during the first stage of propagation. It obeys approximately z3/2 up to ten times the power threshold for solitary wave generation. PMID- 27410887 TI - Experimental evidence of dynamical propagation for solitary waves in ultra slow stochastic non-local Kerr medium. AB - We perform a statistical analysis of the optical solitary wave propagation in an ultra-slow stochastic non-local focusing Kerr medium such as liquid crystals. Our experimental results show that the localized beam trajectory presents a dynamical random walk whose beam position versus the propagation distance z depicts two different kind of evolutions A power law is found for the beam position standard deviation during the first stage of propagation. It obeys approximately z3/2 up to ten times the power threshold for solitary wave generation. PMID- 27410888 TI - Identification of zero density of states domains in band gap fibers using a single binary function. AB - Here we introduce a new calculation method to find the domains of zero density of states for photonic band gap guiding fibers consisting of arrays of high refractive index strands in a low refractive index cladding. We find an analytic expression that associates any combination of geometric parameter, effective index, material and wavelength with a single binary function which allows direct determination whether the density of cladding states is zero or not. The method neither requires the typically used root finding procedure for dispersion tracking nor simulation volume discretization. We verify the validity of our approach on well-established results and reveal as example that band gap regions are mainly determined by the two lowest order Bessel function orders. Our method allows for extensive parameter scans and evaluation of photonic band gap structures against structural and material inaccuracies with substantially reduced simulation effort. PMID- 27410889 TI - Reflectivity of transient Bragg reflection gratings in fiber laser with laser wavelength self-sweeping: erratum. AB - This erratum presents a correction to the computed reflection spectra of transient fiber Bragg gratings that are spontaneously built-up in the ytterbium doped fiber of the fiber laser with laser wavelength self-sweeping. The corrected spectra have high reflectivity reaching values up to 100%. Therefore, they still more support the conclusion drawn in the original paper that self-sweeping is an important mechanism for triggering the self-Q-switched regime with giant pulse generation. PMID- 27410890 TI - Hybrid dielectric light trapping designs for thin-film CdZnTe/Si tandem cells. AB - Tandem solar cells consisting of high bandgap cadmium telluride alloys atop crystalline silicon have potential for high efficiencies exceeding the Shockley Queisser limit. However, experimental results have fallen well below this goal significantly because of non-ideal current matching and light trapping. In this work, we simulate cadmium zinc telluride (CZT) and crystalline silicon (c-Si) tandems as an exemplary system to show the role that a hybrid light trapping and bandgap engineering approach can play in improving performance and lowering materials costs for tandem solar cells incorporating crystalline silicon. This work consists of two steps. First, we optimize absorption in the crystalline silicon layer with front pyramidal texturing and asymmetric dielectric back gratings, which results in 121% absorption enhancement from a planar structure. Then, using this pre-optimized light trapping scheme, we model the dispersion of the CdxZn1-xTe alloys, and then adjust the bandgap to realize the best current matching for a range of CZT thicknesses. Using experimental parameters, the corresponding maximum efficiency is predicted to be 16.08 % for a total tandem cell thickness of only 2.2 MUm. PMID- 27410891 TI - High color-rendering warm-white lamps using quantum-dot color conversion films. AB - Colloidal quantum dots are promising next-generation phosphors to enhance the color rendition of light-emitting diodes (LEDs) while minimizing the brightness droop. In order to exploit the beneficial tunability of quantum dots for highly efficient devices, optimization and determination of the performance limit are of crucial importance. In this work, a facile preparation process of red-emission quantum dot films and simulation algorithm for fitting this film with two commercial LED flat lamps to the optimized performance are developed. Based on the algorithm, one lamp improves from cold-white light (8669 K) with poor color rendition (Ra = 72) and luminous efficacy (85 lm/W) to warm-white light (2867 K) with Ra = 90.8 and R9 = 74.9, and the other reaches Ra = 93 ~ 95. Impressively, the brightness droop is only about 15 ~ 20% and the luminous efficacy of 68 lm/W is achieved. Furthermore, our device shows reliability over 1000 hours with only PET (polyethylene-terephthalate) films as the barrier, indicating that this auxiliary red-emission film can be easily applied to improve the color rendition of most commercial LED flat lamps. PMID- 27410892 TI - Geometrical shape design of nanophotonic surfaces for thin film solar cells. AB - We present the effect of geometrical parameters, particularly shape, on optical absorption enhancement for thin film solar cells based on crystalline silicon (c Si) and gallium arsenide (GaAs) using a rigorous coupled wave analysis (RCWA) method. It is discovered that the "sweet spot" that maximizes efficiency of solar cells exists for the design of nanophotonic surfaces. For the case of ultrathin, rod array is practical due to the effective optical resonances resulted from the optimum geometry whereas parabola array is viable for relatively thicker cells owing to the effective graded index profile. A specific value of thickness, which is the median value of other two devices tailored by rod and paraboloid, is optimized by truncated shape structure. It is therefore worth scanning the optimum shape of nanostructures in a given thickness in order to achieve high performance. PMID- 27410893 TI - Polarized reflectance and transmittance distribution functions of the ocean surface. AB - Two aspects of ocean modelling are treated: representation of ocean waves considering all size-classes of waves and tracing of light-interactions at the wavy sea surface. Nonlinear wave profiles are realized accounting for a wide range of climatologically relevant sea states and wind speeds. Polarized ray tracing is used to investigate air-incident and whitecap-free reflectance and transmittance distributions with high angular resolution subject to sea characterizing parameters, such as significant wave height, peak wave period, wind speed, and surface roughness. Wave-shadowing effects of incident and multiple reflected rays are fully considered. Their influence mostly starts with incidence angles greater than 60 degrees , i.e., when the sun is near the horizon, and is especially pronounced for steep sea states. The net effect of multiple reflections is a redistribution of reflectance and transmittance fractions in their respective hemispheres and a slight increase of the net transmission of light into the sea. Revised reflectance and transmittance distribution functions, RDF and TDF, are provided depending on surface roughness in terms of the mean-square slope; reference is made to other sea state parameters. In comparison with the slope statistics approach, uncertainties related to sun near the horizon are reduced and on average this study yields somewhat higher reflectance values with some variability related to the sea state. By means of provided data, irradiance and radiance reflectances can be computed using desired sky radiance distributions, e.g., clear sky, overcast or partly cloudy sky, as well as wind or sea state information including wave propagation direction. PMID- 27410894 TI - High-brightness source based on luminescent concentration. AB - The concept of a high-luminance light source based on luminescent conversion of LED light and optical concentration in a transparent phosphor is explained. Experiments on a realized light source show that a luminous flux of 8500 lm and a luminance of 500 cd/mm2 can be attained using 56 pump LEDs at 330 W electrical input power. The measurement results are compared to optical simulations, showing that the experimental optical efficiency is slightly lower than expected. The present status enables applications like mid-segment digital projection using LED technology, whereas the concept is scalable to higher fluxes. PMID- 27410895 TI - Light harvesting of silicon nanostructure for solar cells application. AB - Silicon nanostructures have light-harvesting effects for enhancing the performance of solar cells. Based on theoretical investigations on the optical properties of silicon nanowire (Si NW), the influencing laws of the size of Si NW on its light-harvesting effect are proposed. For the first time, we reveal that the resonant wavelength of Si NW predicted by the leaky mode theory does not correspond to the actual resonant wavelength calculated by the discrete dipole approximation method, but exactly coincides with the leftmost wavelength of the resonance peak. Then, the size dependency of the resonant intensity and width of Si NW is different from that of spherical nanoparticles, which can be deduced from the Mie theory. The size dependencies of resonant intensity and width are also applicative for silver/silicon composite nanowires. In addition, it is found that the harvested light by the Si and Ag/Si NW both show significant radial locality feature. The insight in this work is fundamental for the design and fabrication of efficient light -harvesting nanostructures for photovoltaic devices. PMID- 27410896 TI - Optical simulation of photovoltaic modules with multiple textured interfaces using the matrix-based formalism OPTOS. AB - The OPTOS formalism is a matrix-based approach to determine the optical properties of textured optical sheets. It is extended within this work to enable the modelling of systems with an arbitrary number of textured, plane-parallel interfaces. A matrix-based system description is derived that accounts for the optical reflection and transmission interaction between all textured interfaces. Using OPTOS, we calculate reflectance and absorptance of complete photovoltaic module stacks, which consist of encapsulated silicon solar cells featuring textures that operate in different optical regimes. As exemplary systems, solar cells with and without module encapsulation are shown to exhibit a considerable absorptance gain if the random pyramid front side texture is combined with a diffractive rear side grating. A variation of the sunlight's angle of incidence reveals that the grating gain is almost not affected for incoming polar angles up to 60 degrees . Considering as well the good agreement with alternative simulation techniques, OPTOS is demonstrated to be a versatile and efficient method for the optical analysis of photovoltaic modules. PMID- 27410897 TI - Combining near-field hyperspectral imaging and far-field spectral-angular distribution to develop mid-field white LED optical models with spatial color deviation. AB - The integration of spatial distribution of light intensity and color in the midfield is instrumental for LED optical design. On the basis of this rationale, we proposed an accurate and convenient method for developing white LED optical models. Near-field hyperspectral images and far-field spectral-angular distributions were integrated to illustrate changes in spatial light intensity and color distribution in the mid-field, to the exclusion of the absorption, conversion, and scattering of phosphors. The corresponding optical models were developed for three LED samples under different packaging conditions. Their normalized cross-correlation values for spatial light intensity and correlated color-temperature distribution between simulation and measurement averaged as high as 0.995 and 0.99 respectively, which validated the accuracy and feasibility of the proposed method. PMID- 27410898 TI - Optimized tapered dipole nanoantenna as efficient energy harvester. AB - In this paper, a novel design of tapered dipole nanoantenna is introduced and numerically analyzed for energy harvesting applications. The proposed design consists of three steps tapered dipole nanoantenna with rectangular shape. Full systematic analysis is carried out where the antenna impedance, return loss, harvesting efficiency and field confinement are calculated using 3D finite element frequency domain method (3D-FEFD). The structure geometrical parameters are optimized using particle swarm algorithm (PSO) to improve the harvesting efficiency and reduce the return loss at wavelength of 500 nm. A harvesting efficiency of 55.3% is achieved which is higher than that of conventional dipole counterpart by 29%. This enhancement is attributed to the high field confinement in the dipole gap as a result of multiple tips created in the nanoantenna design. Furthermore, the antenna input impedance is tuned to match a wide range of fabricated diode based upon the multi-resonance characteristic of the proposed structure. PMID- 27410899 TI - Implementation of an analytical Raman scattering correction for satellite ocean color processing. AB - Raman scattering of photons by seawater molecules is an inelastic scattering process. This effect can contribute significantly to the water-leaving radiance signal observed by space-borne ocean-color spectroradiometers. If not accounted for during ocean-color processing, Raman scattering can cause biases in derived inherent optical properties (IOPs). Here we describe a Raman scattering correction (RSC) algorithm that has been integrated within NASA's standard ocean color processing software. We tested the RSC with NASA's Generalized Inherent Optical Properties algorithm (GIOP). A comparison between derived IOPs and in situ data revealed that the magnitude of the derived backscattering coefficient and the phytoplankton absorption coefficient were reduced when the RSC was applied, whilst the absorption coefficient of colored dissolved and detrital matter remained unchanged. Importantly, our results show that the RSC did not degrade the retrieval skill of the GIOP. In addition, a time-series study of oligotrophic waters near Bermuda showed that the RSC did not introduce unwanted temporal trends or artifacts into derived IOPs. PMID- 27410900 TI - Diffractive flat panel solar concentrators of a novel design. AB - A novel design for a flat panel solar concentrator is presented which is based on a light guide with a grating applied on top that diffracts light into total internal reflection. By combining geometrical and diffractive optics the geometrical concentration ratio is optimized according to the principles of nonimaging optics, while the thickness of the device is minimized due to the use of total internal reflection. PMID- 27410901 TI - Quantifying PAHs in water by three-way fluorescence spectra and second-order calibration methods. AB - It is still difficult to determine the concentrations of polycyclic aromatic hydrocarbons accurately in natural water by fluorescence technique because of their low solubility, different fluorescent intensity, and the complex interferents from water environments. In this work, three-way fluorescence spectra combined with three methods including three-way parallel factor analysis, multi-way partial least square with residual bilinearization and unfolded partial least square with residual bilinearization were used to predict the concentrations of polycyclic aromatic hydrocarbons at the MUg L-1 level in reservoir and river water, respectively. The prediction abilities of these methods on different analytes were evaluated by validation sets. The results demonstrate that unfolded partial least square with residual bilinearization yields the optimal results with relative error less than or equal to 6% for phenanthrene, pyrene, anthracene and fluorene, and 35% for acenaphthene and fluoranthene in different water backgrounds. PMID- 27410902 TI - Exploration of external light trapping for photovoltaic modules. AB - The reflection of incident sunlight by photovoltaic modules prevents them from reaching their theoretical energy conversion limit. We explore the effectiveness of a universal external light trap that can tackle this reflection loss. A unique feature of external light traps is their capability to simultaneously recycle various broadband sources of reflection on the module level, such as the reflection from the metal front grid, the front interfaces, the reflective backside of the cell, and the white back sheet. The reflected light is recycled in the space between the solar cell and a mirror above the solar cell. A concentrator funnels the light into this cage through a small aperture in the mirror. As a proof-of-principle experiment, a significant reflectance reduction of a bare crystalline silicon (c-Si) photodiode is demonstrated. In contrast to conventional light trapping methods, external light trapping does not induce any damage to the active solar cell material. Moreover, this is a universally applicable technology that enables the use of thin and planar solar cells of superior electrical quality that were so far hindered by limited optical absorption. We considered several trap designs and identified fabrication issues. A series of prototype millimeter-scale external metal light traps were milled and applied on an untextured c-Si photodiode, which is used as a model for future thin solar cells. We determined the concentrator transmittance and analyzed the effect of both the concentration factor and cage height on the absorptance and spatial intensity distribution on the surface of the solar cell. This relatively simple and comprehensive light management solution can be a promising candidate for highly efficient solar modules using thin c-Si solar cells. PMID- 27410903 TI - Ag nanoparticles-embedded surface plasmonic InGaN-based solar cells via scattering and localized field enhancement. AB - Ag nanoparticles are embedded in intentionally etched micro-circle p-GaN holes by means of a thermal agglomeration process to enhance the light absorption efficiency in InGaN/GaN multi-quantum-well (MQW) solar cells. The Ag nanoparticles are theoretically and experimentally verified to generate the plasmon light scattering and the localized field enhancement near the MQW absorption layer. The external quantum efficiency enhancement at a target wavelength region is demonstrated by matching the plasmon resonance of Ag nanoparticles, resulting in a Jsc improvement of 9.1%. Furthermore, the Ag-nanoparticle-embedded InGaN solar cell is effectively fabricated considering the carrier extraction that more than 70% of F.F. and 2.2 V of high Voc are simultaneously attained. PMID- 27410904 TI - Cylindrical array luminescent solar concentrators: performance boosts by geometric effects. AB - This paper presents an investigation of the geometric effects within a cylindrical array luminescent solar concentrator (LSC). Photon concentration of a cylindrical LSC increases linearly with cylinder length up to 2 metres. Raytrace modelling on the shading effects of circles on their neighbours demonstrates effective incident light trapping in a cylindrical LSC array at angles of incidence between 60-70 degrees. Raytrace modelling with real-world lighting conditions shows optical efficiency boosts when the suns angle of incidence is within this angle range. On certain days, 2 separate times of peak optical efficiency can be attained over the course of sunrise-solar noon. PMID- 27410905 TI - Optics of solar central receiver systems: a review. AB - This article reviews the state of the art in optical design, modeling and characterization of solar central receiver systems. PMID- 27410906 TI - Evaluation and phenotypic characteristics of 293 Danish girls with tall stature: effects of oral administration of natural 17beta-estradiol. AB - BACKGROUND: Reduction of adult height by sex steroid treatment was introduced decades ago in tall statured children, but controlled trials are lacking and treatment is controversial. In this study, we wanted to evaluate the phenotypic characteristics in girls referred due to tall stature and the effect of oral administration of 17beta-estradiol on predicted adult height in girls. METHODS: A single-centre retrospective observational study of 304 girls evaluated consecutively due to tall stature between 1993 and 2013. 207 patients diagnosed with constitutionally tall stature (CTS), 60 (29%) girls ended up being treated with 17beta-estradiol with a duration of 1.7 y (1.2; 2.5) (median (25; 75 percentile)), and final height was available in 26 girls. RESULTS: At baseline, 20% of girls with CTS had supranormal IGF-I, whereas reproductive hormones were within the normal range. Final adult height was reduced with 1.6 +/- 2.1 cm in the girls treated with 17beta-estradiol when compared to initial prediction. Chronological age, bone age, estradiol, and IGF-I at baseline or estrogen dose did not predict height reduction. CONCLUSIONS: Serum IGF-I was elevated tall statured children, but did not predict the effect of treatment with 17beta estradiol, which caused a modest reduction in final adult height. PMID- 27410907 TI - Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial. AB - OBJECTIVES: Evaluated the effects of atomoxetine on the reading abilities of children with dyslexia only or attention-deficit/hyperactivity disorder (ADHD) and comorbid dyslexia. METHODS: Children aged 10-16 years (N = 209) met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for dyslexia only (n = 58), ADHD and comorbid dyslexia (n = 124), or ADHD only (n = 27) and were of normal intelligence. Patients were treated with atomoxetine (1.0-1.4 mg/kg/day) or placebo in a 16-week, randomized, placebo-controlled, double-blind trial. The dyslexia-only and ADHD and comorbid dyslexia groups were randomized 1:1; the ADHD-only group received atomoxetine in a blinded manner. Reading abilities were measured with the Woodcock Johnson III (WJIII), Comprehensive Test of Phonological Processing (CTOPP), Gray Oral Reading Tests-4, and Test of Word Reading Efficiency. RESULTS: Atomoxetine-treated dyslexia-only patients compared with placebo patients had significantly greater improvement (p < 0.02) with moderate to approaching high effect sizes (ES) on WJIII Word Attack (ES = 0.72), Basic Reading Skills (ES = 0.48), and Reading Vocabulary (ES = 0.73). In the atomoxetine-treated ADHD and comorbid dyslexia group, improvement on the CTOPP Elision measure (ES = 0.50) was significantly greater compared with placebo (p < 0.02). Total, inattentive, and hyperactive/impulsive ADHD symptom reductions were significant in the atomoxetine treated ADHD and comorbid dyslexia group compared with placebo, and from baseline in the ADHD-only group (p <= 0.02). ADHD symptom improvements in the ADHD and comorbid dyslexia group were not correlated with improvements in reading. CONCLUSIONS: Atomoxetine treatment improved reading scores in patients with dyslexia only and ADHD and comorbid dyslexia. Improvements for patients with dyslexia only were in critical components of reading, including decoding and reading vocabulary. For patients with ADHD and comorbid dyslexia, improvements in reading scores were distinct from improvement in ADHD inattention symptoms alone. These data represent the first report of improvements in reading measures following pharmacotherapy treatment in patients with dyslexia only evaluated in a randomized, double-blind trial. PMID- 27410908 TI - In situ CUTANEOUS CELLULAR IMMUNE RESPONSE IN DOGS NATURALLY AFFECTED BY VISCERAL LEISHMANIASIS. AB - Thirty-eight dogs naturally affected by visceral leishmaniasis were recruited in Aracatuba, Sao Paulo State, Brazil - an endemic area for visceral leishmaniasis. The animals were distributed into one of two groups, according to their clinical and laboratory features, as either symptomatic or asymptomatic dogs. Correlations between clinical features and inflammatory patterns, cellular immune responses, and parasitism in the macroscopically uninjured skin of the ear were investigated. Histological skin patterns were similar in both groups, and were generally characterized by a mild to intense inflammatory infiltrate in the dermis, mainly consisting of mononuclear cells. There was no difference in the number of parasites in the skin (amastigotes/mm2) between the two groups. Concerning the characterization of the cellular immune response, the number of positive inducible nitric oxide synthase (iNOS+) cells was higher in the dermis of symptomatic than in asymptomatic dogs (p = 0.0368). A positive correlation between parasite density and macrophages density (p = 0.031), CD4+ T-cells (p = 0.015), and CD8+ T-cells (p = 0.023) was observed. Furthermore, a positive correlation between density of iNOS+ cells and CD3+ T-cells (p = 0.005), CD4+ T cells (p = 0.001), and CD8+ T-cells (p = 0.0001) was also found. The results showed the existence of a non-specific chronic inflammatory infiltrate in the dermis of dogs affected by visceral leishmaniasis, characterized by the presence of activated macrophages and T-lymphocytes, associated to cutaneous parasitism, independent of clinical status. PMID- 27410909 TI - CUTANEOUS TUBERCULOSIS: A 26-YEAR RETROSPECTIVE STUDY IN AN ENDEMIC AREA OF TUBERCULOSIS, VITORIA, ESPIRITO SANTO, BRAZIL. AB - BACKGROUND: Tuberculosis is a serious health problem in Brazil so that the knowledge on the aspects of cutaneous tuberculosis is medically important. OBJECTIVE: To assess the characteristics of patients with cutaneous tuberculosis treated at the Cassiano Antonio Moraes University Hospital, located in the city of Vitoria, State of Espirito Santo, Brazil. METHODS: This is a retrospective, descriptive, observational and cross-sectional study using the medical records of 29 patients with cutaneous tuberculosis treated at the Dermatology and Pulmonology services of the hospital from 1986 to 2011. The inclusion criterion was the confirmation of cutaneous tuberculosis taking into account clinical, epidemiological, immunological, and bacteriological findings, as well as the response to specific treatment. RESULTS: Of the 29 studied patients; 18 (62%) were women with average age of 37 years; the predominant clinical condition was erythema induratum of Bazin in 12 (41.4%) cases; and the cutaneous lesions were in the lower limbs in 19 (65.8%) patients. Extra-cutaneous involvement occurred in eight (27.6%) cases. The tuberculin tests were positive in 15 (79%) individuals and the assessment of the infectious agent was negative in most of the investigated cases. CONCLUSION: The study found a low frequency (0.44%) of cutaneous tuberculosis in an endemic area of tuberculosis. There was a predominance of infection in women aged thirty to forty years. Erythema induratum was the most common clinical condition, affecting mainly the lower limbs, in contrast to other Brazilian studies that found scrofuloderma as the most common manifestation, predominating in the cervical region of male children and adolescents. PMID- 27410910 TI - SAND FLY SPECIES COMPOSITION (DIPTERA: PSYCHODIDAE: PHLEBOTOMINAE) IN THE MUNICIPALITY OF CANTAGALO , AN AREA WITH SPORADIC CASES OF HUMAN CUTANEOUS LEISHMANIASIS IN RIO DE JANEIRO STATE, BRAZIL. AB - The municipality of Cantagalo is an area with sustained transmission of American Cutaneous Leishmaniasis (ACL). Monthly sand fly collections were performed for three years (June 2012 - May 2015) using a CDC light trap. A total of 3,310 specimens belonging to 12 species were trapped: Nyssomyia intermedia, Nyssomyia whitmani, Migonemyia migonei, Evandromyia lenti, Evandromyia cortelezzii, Micropygomyia quinquefer, Brumptomyia brumpti, Psathyromyia aragaoi, Micropygomyia schreiberi, Pintomyia fischeri, Sciopemyia sordellii, and Evandromyia edwardsi. The last seven species have not been previously recorded in this area. The highest abundance of species occurred between October and March. October was the month with the highest number of captured sand flies, one month before the peak in the summer rainfall. In October the highest number of Ny. intermedia, Ny. whitmani and Mg. migonei, were also collected, the three epidemiologically most important species. The high abundance of species with epidemiological importance for ACL transmission might explain the sporadic occurrence of the disease in the area. PMID- 27410911 TI - DETECTION OF INTESTINAL PARASITES IN THE ENVIRONMENTS OF A PUBLIC SCHOOL IN THE TOWN OF DIAMANTINA , MINAS GERAIS STATE, BRAZIL. AB - Intestinal parasites are a major public health problem in developing countries, most prevalent in areas where sanitation is poor and the population's hygiene is inadequate. They affect people of all ages, although school-age children are the most susceptible. In this study, we investigated the presence of intestinal parasites in the shared environments of a public school in the town of Diamantina, Minas Gerais State. From December 2012 to February 2013, samples were collected for three months (once a month) by using the Graham method (1941), in duplicate, by affixing a 6 x 5 cm clear tape, six times in each collection site, in a space of about 30 cm2. Then, each tape was positioned longitudinally on a microscope slide and the identification of the biological forms of the parasites was performed with the aid of a 40X objective from an optical microscope. Eleven sites were selected for sampling. Cysts of Entamoeba coli were the most frequently found in this study (50%), followed by Hymenolepis diminuta eggs (27.6%), Iodamoeba butschllii cysts (5.6%), Ascaris lumbricoides eggs (5.6%), Taenia species eggs (5.6%) and hookworm eggs (5.6%). The highest positivity rates were found in the samples drawn from the cafeteria's eating table. The results have indicated the need to improve the cleaning in the school environments, as well as the development of educational practices that may help in the preservation of public health. PMID- 27410912 TI - CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY. AB - BACKGROUND: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). METHODS: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. RESULTS: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 +/- 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 +/- 19 vs. 38.6 +/- 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0 153.0, p < 0.001). CONCLUSION: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death. PMID- 27410913 TI - CIPROFLOXACIN RESISTANCE PATTERN AMONG BACTERIA ISOLATED FROM PATIENTS WITH COMMUNITY-ACQUIRED URINARY TRACT INFECTION. AB - OBJECTIVE: To identify the main bacterial species associated with community acquired urinary tract infection (UTI) and to assess the pattern of ciprofloxacin susceptibility among bacteria isolated from urine cultures. METHODS: We conducted a retrospective study in all the patients with community-acquired UTI seen in Santa Helena Laboratory, Camacari, Bahia, Brazil during five years (2010-2014). All individuals who had a positive urine culture result were included in this study. RESULTS: A total of 1,641 individuals met the inclusion criteria. Despite the fact that participants were female, we observed a higher rate of resistance to ciprofloxacin in males. The most frequent pathogens identified in urine samples were Escherichia coli, Klebsiella pneumoniae and Staphylococcus saprophyticus. Antimicrobial resistance has been observed mainly for ampicillin, sulfamethoxazole + trimethoprim and ciprofloxacin. Moreover, E. coli has shown the highest rate of ciprofloxacin resistance, reaching 36% of ciprofloxacin resistant strains in 2014. CONCLUSION: The rate of bacterial resistance to ciprofloxacin observed in the studied population is much higher than expected, prompting the need for rational use of this antibiotic, especially in infections caused by E. coli. Prevention of bacterial resistance can be performed through control measures to limit the spread of resistant microorganisms and a rational use of antimicrobial policy. PMID- 27410914 TI - PREVALENCE AND RISK FACTORS OF SCHISTOSOMIASIS AMONG HAUSA COMMUNITIES IN KANO STATE, NIGERIA. AB - Schistosomiasis remains one of the most prevalent neglected tropical diseases especially in Nigeria which has the greatest number of infected people worldwide. A cross-sectional study was conducted among 551 participants from Kano State, North Central Nigeria. Fecal samples were examined for the presence of Schistosoma mansoni eggs using the formalin-ether sedimentation method while the urine samples were examined using the filtration technique for the presence of S. haematobium eggs. Demographic, socioeconomic and environmental information was collected using a pre-validated questionnaire. The overall prevalence of schistosomiasis was 17.8%, with 8.9% and 8.3% infected with S. mansoni and S. haematobium, respectively and 0.5% presenting co-infection with both species. The multiple logistic regression analysis revealed that age < 18 years (OR = 2.13; 95% CI; 1.34- 3.41), presence of infected family members (OR = 3.98; 95% CI; 2.13 7.46), and history of infection (OR = 2.87; 95% CI; 1.87- 4.56) were the significant risk factors associated with schistosomiasis in these communities. In conclusion, this study revealed that schistosomiasis is still prevalent among Hausa communities in Nigeria. Mass drug administration, health education and community mobilization are imperative strategies to significantly reduce the prevalence and morbidity of schistosomiasis in these communities. PMID- 27410915 TI - EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE. AB - Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis. PMID- 27410916 TI - Bartonella henselae AS A PUTATIVE CAUSE OF CONGENITAL CHOLESTASIS. AB - Severe anemia and cholestatic hepatitis are associated with bartonella infections. A putative vertical Bartonella henselae infection was defined on the basis of ultrastructural and molecular analyses in a three-year-old child with anemia, jaundice and hepatosplenomegaly since birth. Physicians should consider bartonellosis in patients with anemia and hepatitis of unknown origin. PMID- 27410917 TI - CHYLOTHORAX IN PARACOCCIDIOIDOMYCOSIS. AB - A previously healthy, 52-year-old woman presented with a nine months history of low fever and weight loss (> 30 kg). Physical examination disclosed generalized lymphadenopathy, skin lesions, abdominal distension, mild tachypnea and a left breast mass. Laboratory tests showed anemia; (prerenal) kidney injury, low serum albumin level; and negative serology for HIV and viral hepatitis. Computed tomography (neck/chest/abdomen) showed generalized lymph node enlargement, splenomegaly, pleural effusion and ascites. We performed thoracocentesis and paracentesis, and the findings were consistent with chylothorax and chylous ascites (with no neoplastic cells). Biopsies of the breast mass, skin and lymph nodes were performed and all of them showed large round yeast cells with multiple narrow-based budding daughter cells, characteristic of Paracoccidioides brasiliensis. Consequently, paracoccidioidomycosis was diagnosed, and liposomal amphotericin B was prescribed, as well as a high protein and low fat diet (supplemented with medium chain triglycerides). Even so, her clinical status worsened, requiring renal replacement therapy. She evolved with pneumonia, septic shock and respiratory failure and subsequently died. To our knowledge, this is the first description of a case with chylothorax and breast mass due to paracoccidioidomycosis. Additionally, we discuss: 1- the importance of the inclusion of this mycosis in the differential diagnosis of chylothorax and breast mass (breast cancer), especially in endemic areas; and 2- the possible mechanism involved in the development of chylous effusions. PMID- 27410918 TI - ASSOCIATION OF EPSTEIN-BARR VIRUS (EBV) BUT NOT HUMAN PAPILLOMAVIRUS (HPV) WITH GINGIVITIS AND/OR PERIODONTITIS IN TRANSPLANTED INDIVIDUALS. AB - The aim of this study was to investigate the association of EBV and HPV with gingivitis and/or periodontitis according to the immunologic status. To this end, 74 oral biopsies from transplanted and non-transplanted individuals with the abovementioned oral manifestations were submitted to a screening by PCR for both viruses. According to the results, EBV was strongly associated with gingivitis and/or periodontitis in transplanted individuals (p = 0.011) but not HPV (p = 0.766). EBV-HPV co-detections did not enhance the presence of tissue injury as well. Although a causal relationship was not investigated in this study, the higher frequency of these two oncoviruses in lesion tissues must be investigated in follow-up studies, especially among immunocompromised individuals. PMID- 27410919 TI - Scientific Presentation Abstracts 2016 ACVS Surgery Summit October 6-8, Seattle, Washington. PMID- 27410920 TI - The Coming Battle over Shared Savings--Primary Care Physicians versus Specialists. PMID- 27410921 TI - Medicine, Monopoly, and the Premodern State--Early Clinical Trials. PMID- 27410922 TI - Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. AB - BACKGROUND: We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS: In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5 hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (>=70 mg per square meter of body surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS: In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS: Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.). PMID- 27410924 TI - State of Telehealth. PMID- 27410925 TI - IMAGES IN CLINICAL MEDICINE. Milk of Urate Bulla. PMID- 27410923 TI - Ipilimumab for Patients with Relapse after Allogeneic Transplantation. AB - BACKGROUND: Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS: We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS: A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS: Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.). PMID- 27410926 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 21-2016. A 32-Year-Old Man in an Unresponsive State. PMID- 27410927 TI - Recurrent Ventricular Tachycardia--More Drugs or Bring Out the Catheter? PMID- 27410928 TI - CLINICAL DECISIONS. Chemotherapy-Induced Nausea and Vomiting. PMID- 27410929 TI - TBI's Long-Term Follow-up--Slow Progress in Science and Recovery. PMID- 27410930 TI - Prasugrel for Sickle Cell Vaso-Occlusive Events. PMID- 27410931 TI - Prasugrel for Sickle Cell Vaso-Occlusive Events. PMID- 27410932 TI - Oxygen-Saturation Targets in Preterm Infants. PMID- 27410933 TI - Oxygen-Saturation Targets in Preterm Infants. PMID- 27410934 TI - Dexamethasone in Cryptococcal Meningitis. PMID- 27410935 TI - Dexamethasone in Cryptococcal Meningitis. PMID- 27410936 TI - Dexamethasone in Cryptococcal Meningitis. PMID- 27410937 TI - Dexamethasone in Cryptococcal Meningitis. PMID- 27410938 TI - Amoxicillin for Severe Acute Malnutrition in Children. PMID- 27410939 TI - Amoxicillin for Severe Acute Malnutrition in Children. PMID- 27410940 TI - Amoxicillin for Severe Acute Malnutrition in Children. PMID- 27410941 TI - Eliminating Pediatric HIV-1 Infection. PMID- 27410942 TI - Eliminating Pediatric HIV-1 Infection. PMID- 27410944 TI - Removal of Foreign Bodies from the Ear and Nose. PMID- 27410945 TI - Removal of Foreign Bodies from the Ear and Nose. PMID- 27410946 TI - The Cadillac Tax and the Affordable Care Act. PMID- 27410947 TI - The Cadillac Tax and the Affordable Care Act. PMID- 27410948 TI - IMAGES IN CLINICAL MEDICINE. Jejunal Diverticulosis with Midgut Volvulus and Intestinal Malrotation. PMID- 27410949 TI - Metallogels from Coordination Complexes, Organometallic, and Coordination Polymers. AB - A supramolecular gel results from the immobilization of solvent molecules on a 3D network of gelator molecules stabilized by various supramolecular interactions that include hydrogen bonding, pi-pi stacking, van der Waals interactions, and halogen bonding. In a metallogel, a metal is a part of the gel network as a coordinated metal ion (in a discrete coordination complex), as a cross-linking metal node with a multitopic ligand (in coordination polymer), and as metal nanoparticles adhered to the gel network. Although the field is relatively new, research into metallogels has experienced a considerable upsurge owing to its fundamental importance in supramolecular chemistry and various potential applications. This focus review aims to provide an insight into the development of designing metallogelators. Because of the limited scope, discussions are confined to examples pertaining to metallogelators derived from discrete coordination complexes, organometallic gelators, and coordination polymers. This review is expected to enlighten readers on the current development of designing metallogelators of the abovementioned class of molecules. PMID- 27410950 TI - A call for SCAI members to become physician leaders. PMID- 27410951 TI - In multivessel coronary artery disease, a "state-of-the-art" randomized clinical trial of revascularization is needed. AB - Based on this meta-analysis of primarily observational data, complete revascularization (CR) is associated with a reduced risk of death, MI, and repeat revascularization in patients with multivessel coronary artery disease (MVCAD) as compared with incomplete revascularization (IR). Given the current state of evidence, the likelihood of achieving complete revascularization should influence whether PCI or CABG is the best strategy in patients with MVCAD. Given the lack of randomized trials in this area, more robust trial data will address the validity of these findings. PMID- 27410953 TI - PCI in failing saphenous vein grafts: DES trumps BMS for the older patient. AB - PCI to SVG is considered a higher risk intervention requiring clinical judgment, especially in the elderly who may have the oldest and most degenerated SVG conduits. In a cohort of patients with a median age of 75 years who received PCI to SVG with DES, all-cause mortality was lower compared to those receiving BMS, and no difference in MI or urgent revascularization was observed to 3 years. PCI to SVG using DES may be a viable and perhaps superior treatment option for elderly patients. PMID- 27410952 TI - Saphenous vein graft lesions: Are second-generation drug-eluting stents better? AB - Long-term outcomes were similar in patients treated with first- or second generation drug-eluting stents (DES) for saphenous vein graft (SVG) lesions. Patients presenting with acute myocardial infarction as a result of occluded SVG may derive some benefit from the use of second- versus first-generation DES Randomized clinical trials are needed to determine whether newer DES types including those with bioabsorbable polymer or scaffolds offer a distinct advantage in the treatment of SVG lesions. PMID- 27410954 TI - Insulin-treated diabetes mellitus: An important, actionable risk marker after coronary stenting. AB - Insulin treatment for diabetes is a simple but important risk marker for doubled adjusted death and myocardial infarction rates and tripled stent thrombosis risk after coronary stenting. Insulin treatment does not predict meaningfully increased major bleeding or additional revascularization procedures after drug eluting coronary stent implantation. Third generation P2 Y12 receptor antagonists substantially lower risk of events in diabetics after stenting with insulin treated diabetics having twice the magnitude of benefit of diabetics not needing insulin. PMID- 27410955 TI - Inflation time in stent deployment: How long is enough? AB - Coronary stents are commonly deployed using high pressure. However, the duration time of balloon inflation during deployment is still to be determined. Vallurupalli and coworkers, in this issue of CCI, show that the stent system takes an average of 33 sec to "accommodate" its pressure during in vitro deployment. In patients, the mean stent inflation time to achieve pressure stability was 104 seconds, ranging from 30 to 380 sec. These results challenge a rapid inflation/deflation approach for stent deployment. It is suggested that the duration of the inflation might be individualized, in a case-by-case approach. However, the findings must be interpreted with caution, as they cannot be directly extrapolated to more diverse clinical, angiographic, and interventional scenarios. PMID- 27410956 TI - A comparison of the boomerang wire vascular access management system versus manual compression alone during percutaneous diagnostic and interventional cardiovascular procedures. AB - Vascular closure devices allow for early sheath removal, allowing for earlier patient mobilization The Boomerang vascular access management system does not alter arterial integrity for future interventions Access site complications provide significant morbidity in diagnostic and therapeutic interventions. PMID- 27410957 TI - Endothelial function: The canary in the artery. AB - Vascular dysfunction at the level of the brachial artery after transradial cardiac catheterization appears transient and resolves within a week Chemo toxicity from procedural cocktails in addition to catheter-mediated barotrauma directly to the brachial artery or indirectly from radial trauma may play a role in its etiology. Further work is needed to better define the causes of vascular damage from the transradial procedures to develop safer techniques for the future. PMID- 27410958 TI - Same or next day discharge: A new chapter in transcatheter aortic valve implantation. AB - As more patients become eligible for transcatheter aortic valve implantation (TAVI), resource allocation and early discharge planning require careful consideration. TAVI centers must develop locally appropriate and systematic strategies to facilitate early discharge and seamless post-discharge care. While ongoing studies examine pacing requirements post-TAVI, trials comparing general anesthesia and monitored analgesia care are desired. Future technologies for co registration of computed tomography with fluoroscopy may reduce the need for intra-operative transesophageal echo and general anesthesia. A tailored patient centered approach is essential to optimize in-hospital stay and overall patient experience. PMID- 27410959 TI - A glimpse into the future of TAVR. AB - Important differences still exist in the management of patients who receive TAVR in Europe and in the USA. Provisional participation of cardiovascular surgeons and imaging cardiologists, use of TEE, general anesthesia with endotracheal intubation, and length of stay are some of the major differences which may define the future of TAVR in the USA. TAVR procedure will most likely be performed without CT surgery presence and with limited echocardiographic imaging guidance in USA in the near future as it is already being done in Europe. PMID- 27410960 TI - Learning curves for TAVR: Not quite see one, do one teach one. AB - The learning curve for TAVR is determined based on technical (procedural) data from PARTNER-1 Trial The number of cases needed to reach a learning curve for TAVR in PARTNER-1 was 50 for original sites and fell to 25 for late entering sites Analyses such as this is important in developing guidelines for other emerging technologies. PMID- 27410961 TI - Self-Efficacy, Planning, or a Combination of Both? A Longitudinal Experimental Study Comparing Effects of Three Interventions on Adolescents' Body Fat. AB - BACKGROUND: The superiority of an intervention combining two sets of theory-based behavior change techniques targeting planning and self-efficacy over an intervention targeting planning only or self-efficacy only has rarely been investigated. PURPOSE: We compared the influence of self-efficacy, planning, and self-efficacy+planning interventions with an education-based control condition on adolescents' body fat, assuming mediating effects of respective social cognitive variables and moderate-to-vigorous physical activity (MVPA). The moderating role of the built environment was examined. METHODS: Participants (N = 1217, aged 14 18 years) were randomly assigned to four conditions: planning (n = 270), self efficacy (n = 311), self-efficacy+planning (n = 351), and control (n = 285). The measurement was conducted at baseline (T1), two-month follow-up (T2), and fourteen-month follow-up (T3). Interventions/control group procedures were delivered at T1 and T2. Percent of body fat tissue (measured at T1 and T3) was the main outcome. Social cognitive mediators (self-efficacy and planning) were assessed at T1 and T2. The behavioral mediator (MVPA) and the presence of built MVPA facilities (the moderator) were evaluated at T1 and T3. RESULTS: Similar small increases of body fat were found across the three intervention groups, but the increment of body fat was significantly larger in the control group. On average, differences between control and intervention groups translated to approximately 1% of body fat. Effects of the interventions on body fat were mediated by relevant social cognitive variables and MVPA. A lower increase of body fat was found among intervention group participants who had access to newly built MVPA facilities. CONCLUSIONS: We found no superiority of an intervention targeting two social cognitive variables over the intervention targeting one cognition only. PMID- 27410962 TI - SNAP Participants' Eating Patterns over the Benefit Month: A Time Use Perspective. AB - Individuals receiving monthly benefits through the U.S. Supplemental Nutrition Assistance Program (SNAP) often fall short of food at the end of the month and some report feelings of hunger. To investigate this situation, we used time diaries from the 2006-08 American Time Use Survey and Eating & Health Module to identify the timing of days where respondents reported no eating occurrences. Analysis includes descriptive statistics, a logit model, and a simulated benefit month. We found that SNAP participants were increasingly more likely than nonparticipants to report a day with no eating occurrences over the benefit issuance cycle. This supports the view that there is a monthly cycle in food consumption associated with the SNAP monthly benefit issuance policy. PMID- 27410963 TI - Treatment of Chronic Hepatitis C in the Aged - Does It Impact Life Expectancy? A Decision Analysis. AB - BACKGROUND AND AIMS: Recent studies have demonstrated that the efficacy of interferon-free direct-acting antiviral agents (DAAs) in patients over 70 is similar to that of younger age groups. Evidence continues to mount that life expectancy (LE) increases with successful treatment of hepatitis C (HCV) patients with advanced fibrosis. The evidence in older people is more limited. Our aim was to estimate the life year (LY) and quality-adjusted life year (QALY) gained by treatment of naive patients with HCV as a function of patient's age and fibrosis stage. METHODS: We constructed a Markov model of HCV progression toward advanced liver disease. The primary outcome was LY and QALY saved. The model and the sustained virological response of HCV infected subjects treated with a fixed-dose combination of the NS5B polymerase inhibitor Sofosbuvir and the NS5A replication complex inhibitor Ledipasvir were based on the published literature and expert opinion. RESULTS: Generally, both the number of LY gained and QALY gained gradually decreased with advancing age but the rate of decline was slower with more advanced fibrosis stage. For patients with fibrosis stage F1, F2 and F3, LY gained dropped below six months if treated by the age of 55, 65 or 70 years, respectively, while for a patient with fibrosis stage F4, the gain was one LY if treated by the age of 75. The QALY gained for treated over untreated elderly were reasonably high even for those treated at early fibrosis stage. CONCLUSIONS: There is a significant life expectancy benefit to HCV treatment in patients up to age 75 with advanced-stage fibrosis. PMID- 27410965 TI - Urinary Incontinence as a Predictor of Death: A Systematic Review and Meta Analysis. AB - BACKGROUND: The association between urinary incontinence (UI) and increased mortality remains controversial. The objective of our study was to evaluate if this association exists. METHODS: We performed a systematic review and meta analysis of observational studies comparing death rates among patients suffering from UI to those without incontinence. We searched in Medline, Embase and the Cochrane library using specific keywords. Studies exploring the post-stroke period were excluded. Hazard ratios (HR) were pooled using models with random effects. We stratified UI by gender and by UI severity and pooled all models with adjustment for confounding variables. RESULTS: Thirty-eight studies were retrieved. When compared to non-urinary incontinent participants, UI was associated with an increase in mortality with pooled non adjusted HR of 2.22 (95%CI 1.77-2.78). The risk increased with UI severity: 1.24 (95%CI: 0.79-1.97) for light, 1.71 (95%CI: 1.26-2.31) for moderate, and 2.72 (95%CI: 1.90-3.87) for severe UI respectively. When pooling adjusted measures of association, the resulting HR was 1.27 (95%CI: 1.13-1.42) and increased progressively for light, moderate and severe UI: 1.07 (95%CI: 0.79-1.44), 1.25 (95%CI: 0.99-1.58), and 1.47 (95%CI: 1.03-2.10) respectively. There was no difference between genders. CONCLUSION: UI is a predictor of higher mortality in the general and particularly in the geriatric population. The association increases with the severity of UI and persists when pooling models adjusted for confounders. It is unclear if this association is causative or just reflects an impaired general health condition. As in most meta-analyses of observational studies, methodological issues should be considered when interpreting results. PMID- 27410964 TI - Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice. AB - In blind individuals, visually deprived occipital areas are activated by non visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An), was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed. PMID- 27410966 TI - Age Targeting of Voluntary Medical Male Circumcision Programs Using the Decision Makers' Program Planning Toolkit (DMPPT) 2.0. AB - BACKGROUND: Despite considerable efforts to scale up voluntary medical male circumcision (VMMC) for HIV prevention in priority countries over the last five years, implementation has faced important challenges. Seeking to enhance the effect of VMMC programs for greatest and most immediate impact, the U. S. President's Plan for AIDS Relief (PEPFAR) supported the development and application of a model to inform national planning in five countries from 2013 2014. METHODS AND FINDINGS: The Decision Makers' Program Planning Toolkit (DMPPT) 2.0 is a simple compartmental model designed to analyze the effects of client age and geography on program impact and cost. The DMPPT 2.0 model was applied in Malawi, South Africa, Swaziland, Tanzania, and Uganda to assess the impact and cost of scaling up age-targeted VMMC coverage. The lowest number of VMMCs per HIV infection averted would be produced by circumcising males ages 20-34 in Malawi, South Africa, Tanzania, and Uganda and males ages 15-34 in Swaziland. The most immediate impact on HIV incidence would be generated by circumcising males ages 20-34 in Malawi, South Africa, Tanzania, and Uganda and males ages 20-29 in Swaziland. The greatest reductions in HIV incidence over a 15-year period would be achieved by strategies focused on males ages 10-19 in Uganda, 15-24 in Malawi and South Africa, 10-24 in Tanzania, and 15-29 in Swaziland. In all countries, the lowest cost per HIV infection averted would be achieved by circumcising males ages 15-34, although in Uganda this cost is the same as that attained by circumcising 15- to 49-year-olds. CONCLUSIONS: The efficiency, immediacy of impact, magnitude of impact, and cost-effectiveness of VMMC scale-up are not uniform; there is important variation by age group of the males circumcised and countries should plan accordingly. PMID- 27410968 TI - The Role of Subtractive Color Mixing in the Perception of Blue Nevi and Veins Beyond the Tyndall Effect. PMID- 27410967 TI - The Gut Microbiota from Lean and Obese Subjects Contribute Differently to the Fermentation of Arabinogalactan and Inulin. AB - BACKGROUND: An aberrant metabolic activity or a compositional alteration of the gut microbiota has been proposed as a factor that makes us more prone to disease. Therefore, we explored the effect of two dietary fibers (arabinogalactan and inulin) on the microbiota from lean and obese subjects during 72 h in vitro fermentation experiments using the validated TNO dynamic in vitro model of the proximal colon: TIM-2. Metabolically, arabinogalactan fermentation showed a higher production of propionate when compared to n-butyrate in the obese microbiota fermentations. In general, lean microbiota produced more n-butyrate from the fermentation of both substrates when compared to the obese microbiota. Furthermore, the obese microbiota extracted more energy from the fermentation of both fibers. RESULTS: Compositionally, bacteria belonging to Gemmiger, Dorea, Roseburia, Alistipes, Lactobacillus and Bifidobacterium genera were found to be highly abundant or stimulated by the prebiotics in the lean microbiota suggesting a potential role in leanness. Furthermore, a significant correlation between known butyrogenic strains including B. adolescentis, an unclassified Bifidobacterium and F. prausnitzii with this metabolite in the fermentation of inulin in both microbiotas was found. CONCLUSIONS: Although supplementary in vivo studies are needed, the current study provides more evidence for the consumption of specific ingredients with the aim of modulating the gut microbiota in the context of obesity. PMID- 27410971 TI - Burn Carbohydrates, Not Hydrocarbons. PMID- 27410972 TI - Letters. PMID- 27410969 TI - Climate Change Impairs Nitrogen Cycling in European Beech Forests. AB - European beech forests growing on marginal calcareous soils have been proposed to be vulnerable to decreased soil water availability. This could result in a large scale loss of ecological services and economical value in a changing climate. In order to evaluate the potential consequences of this drought-sensitivity, we investigated potential species range shifts for European beech forests on calcareous soil in the 21st century by statistical species range distribution modelling for present day and projected future climate conditions. We found a dramatic decline by 78% until 2080. Still the physiological or biogeochemical mechanisms underlying the drought sensitivity of European beech are largely unknown. Drought sensitivity of beech is commonly attributed to plant physiological constraints. Furthermore, it has also been proposed that reduced soil water availability could promote nitrogen (N) limitation of European beech due to impaired microbial N cycling in soil, but this hypothesis has not yet been tested. Hence we investigated the influence of simulated climate change (increased temperatures, reduced soil water availability) on soil gross microbial N turnover and plant N uptake in the beech-soil interface of a typical mountainous beech forest stocking on calcareous soil in SW Germany. For this purpose, triple 15N isotope labelling of intact beech seedling-soil-microbe systems was combined with a space-for-time climate change experiment. We found that nitrate was the dominant N source for beech natural regeneration. Reduced soil water content caused a persistent decline of ammonia oxidizing bacteria and therefore, a massive attenuation of gross nitrification rates and nitrate availability in the soil. Consequently, nitrate and total N uptake of beech seedlings were strongly reduced so that impaired growth of beech seedlings was observed already after one year of exposure to simulated climatic change. We conclude that the N cycle in this ecosystem and here specifically nitrification is vulnerable to reduced water availability, which can directly lead to nutritional limitations of beech seedlings. This tight link between reduced water availability, drought stress for nitrifiers, decreased gross nitrification rates and nitrate availability and finally nitrate uptake by beech seedlings could represent the Achilles' heel for beech under climate change stresses. PMID- 27410973 TI - A need to know. PMID- 27410974 TI - Scanning sports. PMID- 27410975 TI - Brief reports. PMID- 27410976 TI - Coming in sportsmedicine. PMID- 27410977 TI - Every Patient an Athlete. PMID- 27410979 TI - Tranquilizer Effect of Exercise: A Critical Review. AB - In brief: Evidence suggests that none of the currently used tranquilizer drugs can be used without risking side effects and/or addiction. Many people have contended that physical exercise relieves anxiety, but until recently no experimental evidence has supported this subjective conclusion. Dr. deVries examined this hypothesis by reviewing available data and surveys of expert opinion and controlled psychological and physiological experiments. He believes that appropriate types, intensities, and durations of exercise can produce a significant tranquilizer effect. Rhythmic exercise such as walking, jogging, cycling, and bench stepping for 5 to 30 minutes at 30% to 60% of maximum intensity was most effective. PMID- 27410981 TI - The Effect of Rapid Weight Loss on Physiological Functions in Wrestlers. AB - In brief: To assess the effects of rapid weight reduction, four university wrestlers decreased their body weight by 8% over a four-day period by food and liquid intake reductions. Significant decreases in muscle glycogen concentration and dynamic strength, but not aerobic or anaerobic capacity, accompanied weight loss. A three-hour rehydration period did not improve glycogen levels or strength performance. These results suggest that rapid weight reduction may impair wrestling performance. PMID- 27410980 TI - Developing a Stretching Program. AB - In brief: Although stretching exercises can prevent muscle injuries and enhance athletic performance, they can also cause injury. The author explains the four most common types of stretching exercises and explains why he considers static stretching the safest. He also sets up a stretching routine for runners. In setting up a safe stretching program, one should (1) precede stretching exercises with a mild warm-up; (2) use static stretching; (3) stretch before and after a workout; (4) begin with mild and proceed to moderate exercises; (5) alternate exercises for muscle groups; (6) stretch gently and slowly until tightness, not pain, is felt; and (7) hold the position for 30 to 60 seconds. PMID- 27410982 TI - Catastrophic Neck Injuries From Football in Western Pennsylvania. AB - In brief: In an effort to determine common factors that may have contributed to spinal cord injuries in football players, the author reviewed medical records and newspaper articles. He also interviewed players who had sustained catastrophic neck injuries and talked to their families and coaches. The study showed that lightweight defensive players are at the greatest risk of suffering catastrophic neck injuries, which are most often due to improper use of the head and neck during tackling. Coaches, trainers, and team physicians should institute proper conditioning and development programs and teach correct blocking and tackling techniques to prevent these injuries. PMID- 27410983 TI - Theory and Management of Exercise-Related Hematuria. AB - In brief: The pathogenesis of exercise- related hematuria is not clearly understood. This review shows that the most important factors are the degree of aerobic demand and the duration of exercise. Dehydration, age, and diet are also implicated. The authors propose a theory based on increased vascular resistance, cortical shunting, and spiral calicine vessels. They say the problem seems to be benign, because athletes have no increased incidence of renal disease. After the initial evaluation to rule out occult urologic pathology, recurrences do not require complete reevaluation if they are characteristic of the previous episodes and if the urine clears in 24 to 48 hours. PMID- 27410984 TI - Menstrual Changes in Athletes. AB - In brief: Menstrual irregularity in athletes, once thought to be a phenomenon isolated to endurance athletes, is being widely reported as more women engage in intense exercise. It could stem from physical or psychological stress, changes in hormone function or body composition, or a combination of these factors. This panel of experts helped to define the problem, but they agreed that research is confounded by the many variables involved. Until the answers are in, athletes should not assume that changes in their menstrual cycles stem from exercise alone. They should consult a gynecologist to rule out pathological changes. PMID- 27410985 TI - Trainers for High School Athletes: Seattle Develops a Model Program. AB - Seattle high schools use a health care team of physicians, coaches, and student athletic trainers to systematically evaluate, rehabilitate, and monitor sports injuries. PMID- 27410986 TI - John D. Cantwell: A Dedication to Preventive Cardiology, Writing, and Sports. AB - Atlanta physician John D. Cantwell's outlook on life reflects his professional interests in preventive medicine and lifetime sports and his personal commitments to travel, writing, and his family. PMID- 27410987 TI - Action arena. PMID- 27410988 TI - Sportsmedicine Cold War? AB - Three years before the Los Angeles Olympic Games. Michael Yessis, PhD. believes the United States has as much chance of garnering the lion's share of the medals as Albania or Zambia. The professor of physical education at California State University, Fullerton, and publisher o f the Soviet Sports Review told McGraw Hill World News reporter Paul Addison that he is not a pessimist or communist. He just doesn't expect any nation to match the excellence of the scientifically trained Soviet athletes. Yessis writes here for a change in attitude toward learning from the Russians. PMID- 27410989 TI - Hawaii: A Sporting Excursion on the Big Island. AB - In this recreational paradise, opportunities for golf, tennis, and water sports abound; but one can also make a sport of merely driving and exploring its beautiful volcanic shores and mountains. PMID- 27410991 TI - Ankle Edema and Galvanic Muscle Stimulation. PMID- 27410993 TI - Enantioselective Hydrogenation of Diarylmethanimines for Synthesis of Chiral Diarylmethylamines. AB - An enantioselective hydrogenation of N-substituted diarylmethanimines under mild conditions has been first realized by using an iridium catalyst with a chiral f spiroPhos ligand. This method provides an efficient access to the asymmetric synthesis of a variety of chiral diarylmethylamines and their derivatives with excellent enantioselectivities (up to 99.4% ee) and high turnover numbers (TON up to 4000). PMID- 27410994 TI - Erratum. AB - [This corrects the article DOI: 10.1016/S0377-1237(05)80057-7.]. PMID- 27410995 TI - Ribosomal S6 kinase (RSK) modulators: a patent review. AB - INTRODUCTION: The p90 ribosomal S6 kinases (RSK) are a family of Ser/Thr protein kinases that are downstream effectors of MEK1/2-ERK1/2. Increased RSK activation is implicated in the etiology of multiple pathologies, including numerous types of cancers, cardiovascular disease, liver and lung fibrosis, and infections. AREAS COVERED: The review summarizes the patent and scientific literature on small molecule modulators of RSK and their potential use as therapeutics. The patents were identified using World Intellectual Property Organization and United States Patent and Trademark Office databases. The compounds described are predominantly RSK inhibitors, but a RSK activator is also described. The majority of the inhibitors are not RSK-specific. EXPERT OPINION: Based on the overwhelming evidence that RSK is involved in a number of diseases that have high mortalities it seems surprising that there are no RSK modulators that have pharmacokinetic properties suitable for in vivo use. MEK1/2 inhibitors are in the clinic, but the efficacy of these compounds appears to be limited by their side effects. We hypothesize that targeting the downstream effectors of MEK1/2, like RSK, are an untapped source of drug targets and that they will generate less side effects than MEK1/2 inhibitors because they regulate fewer effectors. PMID- 27410996 TI - Community Implementation of a Prehospital Spinal Immobilization Guideline. AB - OBJECTIVE: The purpose of this study was to qualitatively describe the underpinnings of the successful implementation of a collaborative prehospital spinal immobilization guideline throughout the emergency medical services (EMS) community in two counties in Colorado. We also describe lessons learned that may be beneficial to other communities considering similar initiatives. METHODS: Qualitative data were collected from key informants who were directly involved in the implementation of a new prehospital spinal immobilization guideline among four community hospitals in two different hospital systems and the associated EMS providers within the two counties. We interviewed a purposively selected sample of emergency department (ED) physicians and other ED staff, hospital decision makers, EMS educators as well as fire department and EMS medical directors. Data were collected and reviewed until saturation was achieved. We conducted qualitative analysis to summarize and synthesize themes. RESULTS: Ten key informants were interviewed, at which point saturation was achieved and several clear themes emerged. Participants described successful community-wide guideline implementation despite a history of competition, isolation, and conflict between the various EMS organizations and hospitals on past EMS and trauma initiatives. Factors related to success included the nearly universal perception that the initiative was "cutting edge" and thus an important paradigm shift in care for the community, as a whole. Participants reported the ability of community stakeholders to jointly assure a collaborative approach, characterized by intensive education for EMS personnel and others involved, and the ability of the community to together secure the new equipment required for success. CONCLUSIONS: Key informants described a convergence of factors as leading to the successful implementation of a prehospital spinal immobilization guideline. Lessons learned regarding how to overcome a tradition of competition and isolation to allow for success may be useful to other communities considering similar initiatives. PMID- 27410997 TI - [Guideline for the anaesthetic management of dogs and cats]. PMID- 27410998 TI - Failure of ossification of the occipital bone in mandibuloacral dysplasia type B. AB - Mandibuloacral dysplasia with type B lipodystrophy is a rare autosomal recessive disease characterized by atrophic skin, lipodystrophy, and skeletal features. It is caused by mutations in ZMPSTE24, a gene encoding a zinc metalloproteinase involved in the post-translational modification of lamin. Nine distinct pathogenic variants have been identified in 11 patients from nine unrelated families with this disorder. We report a 12-year-old boy with mandibuloacral dysplasia with type B lipodystrophy and a novel homozygous c.1196A>G; p.(Tyr399Cys) mutation in ZMPSTE24. The patient had typical dermatological and skeletal features of mandibuloacral dysplasia with type B lipodystrophy, sparse hair, short stature, mild microcephaly, facial dysmorphism, and a striking failure of ossification of the interparietal region of the occipital bone, up to the position where transverse occipital suture can be observed. Newly recognized signs for mandibuloacral dysplasia with type B lipodystrophy were gaze palsy and ptosis. Delayed closure of cranial sutures and Wormian bones have been described in three patients, but an ossification failure strictly limited to the occipital bone, as seen in the present patient, appears to be unique for mandibuloacral dysplasia with type B lipodystrophy. This observation illustrates that ZMPSTE24 could play a specific role in membranous ossification in the interparietal part of the squama (Inca bone) but not in the intracartilaginous ossification of the supraoccipital. This failure of ossification in the squama appears to be a useful feature for the radiological diagnosis of mandibuloacral dysplasia with type B lipodystrophy. (c) 2016 Wiley Periodicals, Inc. PMID- 27410999 TI - Adult asthma is associated with an increased risk of herpes zoster: A population based cohort study. AB - OBJECTIVE: The objective of this study was to determine whether a new diagnosis of asthma is associated with a later diagnosis of herpes zoster (HZ) in a nationwide, retrospective, non-age limited, population-based cohort. METHODS: We used data from the National Health Insurance Research Database in Taiwan. The asthma group consisted of all 40 069 patients in the database with newly diagnosed asthma and using asthma medications from 2000 through 2005. The nonasthma group comprised 40 069 age- and sex-matched patients without any asthma diagnosis. Cox proportional hazards regression analysis was applied to calculate the hazard ratio of HZ in the patients with asthma relative to those without asthma. RESULTS: During a mean follow-up period of 8.77 years, the risk of HZ was 1.48-fold higher in the asthma group compared with that in the nonasthma group after adjustment for sex, age, comorbidities, inhaled and systemic corticosteroid use, and annual outpatient department visits to dermatologists. Additional stratified analyses revealed that the risk of HZ was significantly higher in patients of both sexes and those aged older than 21 years. CONCLUSIONS: Newly diagnosed adult patients with asthma have a significantly higher risk of developing HZ than do those without asthma. PMID- 27411000 TI - Narrator Point of View and Persuasion in Health Narratives: The Role of Protagonist-Reader Similarity, Identification, and Self-Referencing. AB - Narratives are often used in messages about health threats. We posited that a 1st person point of view (POV) narrative would have a greater effect than a 3rd person POV on the mediators identification and self-referencing-an effect moderated by protagonist-reader similarity. Higher levels of identification and self-referencing were expected to elevate susceptibility and severity perceptions, leading to persuasion. Participants ages <=30 years were recruited from a crowdsource website and randomly assigned to read one version of a faux magazine article about caffeine overdose. Article versions were defined by a 2 (1st- or 3rd-person POV) * 2 (similar or dissimilar protagonist) design. To manipulate similarity, we had respondents read an article in which the protagonist was also young (24 years of age) and of the same sex or much older (54 years of age) and of the opposite sex. Participants then completed a questionnaire measuring study variables. Contrary to expectations, POV did not affect identification or self-referencing. However, similarity directly impacted identification, which in turn influenced severity perceptions. Self-referencing was not affected by the experimental manipulations but had a direct effect on susceptibility and also mediated the identification -> susceptibility relationship. Susceptibility and severity perceptions were associated with greater levels of persuasion. Implications for message design are discussed. PMID- 27411001 TI - Of Mouse Models of Mast Cell Deficiency and Metabolic Syndrome. PMID- 27411002 TI - Expanding Our Understanding of mtDNA Deletions. AB - Clonal expansion of mtDNA deletions compromises mitochondrial function in human disease and aging, but how deleterious mtDNA genomes propagate has remained unclear. In this issue (Gitschlag et al., 2016) and in a recent Nature publication, C. elegans studies implicate the mitochondrial unfolded protein response (UPR(mt)) and offer mechanistic insights into this process. PMID- 27411003 TI - Metabolic Acceleration in Human Evolution. AB - Humans stand out among other primates by an unusual combination of a very large brain and high fertility. Pontzer et al. (2016a) present new data on daily energy expenditure in great apes and show that the metabolic rate increased during human evolution. PMID- 27411004 TI - Elevated GDF11 Is a Risk Factor for Age-Related Frailty and Disease in Humans. AB - GDF11 was reported to decline with age and to have muscle and heart rejuvenating effects. These reports were disputed. A Cell Metabolism paper now shows that in human beings, GDF11 does not decline with age and is actually a risk factor for frailty and other morbidities (Schafer et al., 2016). PMID- 27411005 TI - Microbially Produced Acetate: A "Missing Link" in Understanding Obesity? AB - Numerous studies have connected the gut microbiome with diet-induced obesity; however, mechanistic explanations for the host-microbial interactions are needed. Perry et al. (2016) present studies suggesting that microbially produced acetate (MPA) increases post-prandial insulin release via a sequential and integrated gut, brain, and pancreatic signaling network promoting energy retention. PMID- 27411006 TI - Pink Light on Mitochondria in Autoimmunity and Parkinson Disease. AB - Mitochondrial dysfunction and T cell autoimmunity have been independently implicated in Parkinson disease pathogenesis. In a recent publication in Cell, Matheoud et al. (2016) link them by describing a new mechanism, activated in familial forms of Parkinson disease, in which mitochondrial proteins are processed for recognition by CD8+ T cells. PMID- 27411007 TI - Transomics: Mitochondrial Systems Analyses Get Supercomplex. AB - New "omics" tools are accelerating our ability to connect genomic variation to complex traits. Williams et al. (2016) reveal the power of layering quantitative proteomics and metabolomics measurements into a "systems genetics" analysis of recombinant inbred mouse strains to unravel new aspects of mitochondrial metabolism. PMID- 27411008 TI - Unimolecular Polypharmacy for Treatment of Diabetes and Obesity. AB - Many complex diseases have historically proven to be defiant to the best mono therapeutic approaches. Several examples of combination therapies have largely overcome such challenges, notably for the treatment of severe hypertension and tuberculosis. Obesity and its consequences, such as type 2 diabetes, have proven to be equally resistant to therapeutic approaches based on single medicines. Proper management of type 2 diabetes often requires adjunctive medications, and the recent registration of a few compound mixtures has set the precedent for combinatorial treatment of obesity. On the other hand, double or triple therapeutic combinations are more difficult to advance to regulatory approval than single molecules. More recently, several classes of novel unimolecular combination therapeutics have emerged with superior efficacy than currently prescribed options and pose the potential to reverse obesity and type 2 diabetes. Here, we summarize the discovery, pre-clinical validation, and first clinical test of such peptide hormone poly-agonist drug candidates. PMID- 27411010 TI - Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response. AB - Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat. PMID- 27411009 TI - Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial. AB - The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7 day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. PMID- 27411011 TI - Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans. AB - Mutant mitochondrial genomes (mtDNA) can be viewed as selfish genetic elements that persist in a state of heteroplasmy despite having potentially deleterious metabolic consequences. We sought to study regulation of selfish mtDNA dynamics. We establish that the large 3.1-kb deletion-bearing mtDNA variant uaDf5 is a selfish genome in Caenorhabditis elegans. Next, we show that uaDf5 mutant mtDNA replicates in addition to, not at the expense of, wild-type mtDNA. These data suggest the existence of a homeostatic copy-number control that is exploited by uaDf5 to "hitchhike" to high frequency. We also observe activation of the mitochondrial unfolded protein response (UPR(mt)) in uaDf5 animals. Loss of UPR(mt) causes a decrease in uaDf5 frequency, whereas its constitutive activation increases uaDf5 levels. UPR(mt) activation protects uaDf5 from mitophagy. Taken together, we propose that mtDNA copy-number control and UPR(mt) represent two homeostatic response mechanisms that play important roles in regulating selfish mitochondrial genome dynamics. PMID- 27411012 TI - Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation. AB - Naive T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naive CD4(+) T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one-carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one-carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one-carbon metabolism that is critical for T cell activation and survival. PMID- 27411013 TI - Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function. AB - Brown (BAT) and white (WAT) adipose tissues play distinct roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to non alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a cellular energy sensor, but its role in regulating BAT and WAT metabolism is unclear. We generated an inducible model for deletion of the two AMPK beta subunits in adipocytes (ibeta1beta2AKO) and found that ibeta1beta2AKO mice were cold intolerant and resistant to beta-adrenergic activation of BAT and beiging of WAT. BAT from ibeta1beta2AKO mice had impairments in mitochondrial structure, function, and markers of mitophagy. In response to a high-fat diet, ibeta1beta2AKO mice more rapidly developed liver steatosis as well as glucose and insulin intolerance. Thus, AMPK in adipocytes is vital for maintaining mitochondrial integrity, responding to pharmacological agents and thermal stress, and protecting against nutrient-overload-induced NAFLD and insulin resistance. PMID- 27411014 TI - Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation. AB - The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased (18)fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16 degrees C-17 degrees C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health. PMID- 27411015 TI - Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis. AB - Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. PMID- 27411017 TI - Modulating the hydration behaviour of calcium chloride by lactam complexation. AB - Complexation of calcium chloride with bis(lactam) ligand L1 allows the formation of both an unstable anhydrous complex, an aqua complex {[Ca2(MU-L1)2(H2O)9]Cl4]}n (1) and a related hydrate incorporating additional lattice water of crystallization {[Ca(MU-L1)(H2O)5]Cl2.H2O}n (2). Related mono(lactam) L2 does not form aqua complexes but the anhydrous complex {[CaCl2(MU-L2)2]}n (3), is highly deliquescent. An unusual ethanol solvate is also reported {[CaCl2(L2)(EtOH)]}n (4). PMID- 27411016 TI - Assessment of Hepatic Mitochondrial Oxidation and Pyruvate Cycling in NAFLD by (13)C Magnetic Resonance Spectroscopy. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and there is great interest in understanding the potential role of alterations in mitochondrial metabolism in its pathogenesis. To address this question, we assessed rates of hepatic mitochondrial oxidation in subjects with and without NAFLD by monitoring the rate of (13)C labeling in hepatic [5 (13)C]glutamate and [1-(13)C]glutamate by (13)C MRS during an infusion of [1 (13)C]acetate. We found that rates of hepatic mitochondrial oxidation were similar between NAFLD and control subjects. We also assessed rates of hepatic pyruvate cycling during an infusion of [3-(13)C]lactate by monitoring the (13)C label in hepatic [2-(13)C]alanine and [2-(13)C]glutamate and found that this flux was also similar between groups and more than 10-fold lower than previously reported. Contrary to previous studies, we show that hepatic mitochondrial oxidation and pyruvate cycling are not altered in NAFLD and do not account for the hepatic fat accumulation. PMID- 27411018 TI - Euthanasia and Surgery Concerning the Belgian law on Euthanasia (dd. May 28, 2002 published June 22, 2002). PMID- 27411019 TI - Euthanasia as an example of conflict between ethical precepts and entitlement rights. A surgeon's viewpoint(). PMID- 27411020 TI - Uiteenzetting Tijdens het Euthanasiedebat in de Commissie voor de Justitie van de Kamer van Volksvertegenwoordigers. PMID- 27411021 TI - Document d'enregistrement Euthanasie - Registratiedocument Euthanasie. PMID- 27411022 TI - Multiple myeloma: patient outcomes in real-world practice. AB - With increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first-line therapy was 6 months, followed by a median treatment-free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician-judged. Toxicities and co-morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice. PMID- 27411024 TI - [Correction: Value of Pressure Measurements: Methods and Sources of Errors]. PMID- 27411025 TI - Questionnaire-based assessment of executive functioning: Case studies. AB - Delays in the development of executive functioning skills are frequently observed in pediatric neuropsychology populations and can have a broad and significant impact on quality of life. As a result, assessment of executive functioning is often relevant for the development of formulations and recommendations in pediatric neuropsychology clinical work. Questionnaire-based measures of executive functioning behaviors in everyday life have unique advantages and complement traditional neuropsychological measures of executive functioning. Two case studies of children with spina bifida are presented to illustrate the clinical use of a new questionnaire measure of executive and learning-related functioning, the Learning, Executive, and Attention Functioning Scale (LEAF). The LEAF emphasizes clinical utility in assessment by incorporating four characteristics: brevity in administration, breadth of additional relevant content, efficiency of scoring and interpretation, and ease of availability for use. LEAF results were consistent with another executive functioning checklist in documenting everyday behavior problems related to working memory, planning, and organization while offering additional breadth of assessment of domains such as attention, processing speed, and novel problem-solving. These case study results demonstrate the clinical utility of questionnaire-based measurement of executive functioning in pediatric neuropsychology and provide a new measure for accomplishing this goal. PMID- 27411026 TI - Mechanisms of Local Stress Sensing in Multifunctional Polymer Films Using Fluorescent Tetrapod Nanocrystals. AB - Nanoscale stress-sensing can be used across fields ranging from detection of incipient cracks in structural mechanics to monitoring forces in biological tissues. We demonstrate how tetrapod quantum dots (tQDs) embedded in block copolymers act as sensors of tensile/compressive stress. Remarkably, tQDs can detect their own composite dispersion and mechanical properties with a switch in optomechanical response when tQDs are in direct contact. Using experimental characterizations, atomistic simulations and finite-element analyses, we show that under tensile stress, densely packed tQDs exhibit a photoluminescence peak shifted to higher energies ("blue-shift") due to volumetric compressive stress in their core; loosely packed tQDs exhibit a peak shifted to lower energies ("red shift") from tensile stress in the core. The stress shifts result from the tQD's unique branched morphology in which the CdS arms act as antennas that amplify the stress in the CdSe core. Our nanocomposites exhibit excellent cyclability and scalability with no degraded properties of the host polymer. Colloidal tQDs allow sensing in many materials to potentially enable autoresponsive, smart structural nanocomposites that self-predict impending fracture. PMID- 27411027 TI - Fall-related injuries in Amsterdam: Frail older women at risk. AB - Unintentional falls are a common cause of injury, especially among older persons. This study evaluates risk factors such as gender and age on morbidity and mortality after unintentional falls. Data were collected retrospectively for patients with a unintentional fall who were presented to the emergency department in 2013. A total of 3,217 patients were included; the majority were female. Patients over 65 years of age had a significant higher mortality and a longer length of hospital stay. Older women are at risk for sustaining a fall-related injury. Female gender is furthermore associated with increased length of stay in the hospital. Prevention should focus especially on these frail patients. PMID- 27411028 TI - Discovery of Covalent Ligands via Noncovalent Docking by Dissecting Covalent Docking Based on a "Steric-Clashes Alleviating Receptor (SCAR)" Strategy. AB - Covalent ligands modulating protein activities/signals have attracted unprecedented attention in recent years, but the insufficient understanding of their advantages in the early days of drug discovery has hindered their rational discovery and development. This also left us inadequate knowledge on the rational design of covalent ligands, e.g., how to balance the contribution from the covalent group and the noncovalent group, respectively. In this work, we dissected the noncovalent docking from covalent docking by creating SCARs (steric clashes alleviating receptors). We showed that the SCAR method outperformed those specifically developed but more complicated covalent docking protocols. We furthermore provided a "proof-of-principle" example by implementing this method in the first high-throughput screening and discovery of novel covalent inhibitors of S-adenosylmethionine decarboxylase. This work demonstrated that noncovalent groups play a predeterminate role in the design of covalent ligands, and would be of great value in accelerating the discovery and development of covalent ligands. PMID- 27411023 TI - Recent advances and future of immunotherapy for glioblastoma. AB - INTRODUCTION: Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival benefit observed with immunotherapies in cancers such as melanoma and prostate cancer has fuelled research into evaluating immunotherapies for GBM. AREAS COVERED: Preclinical studies have brought a wealth of information for improving the prognosis of GBM and multiple clinical studies are evaluating a wide array of immunotherapies for GBM patients. This review highlights advances in the development of immunotherapeutic approaches. We discuss the strategies and outcomes of active and passive immunotherapies for GBM including vaccination strategies, gene therapy, check point blockade and adoptive T cell therapies. We also focus on immunoediting and tumor neoantigens that can impact the efficacy of immunotherapies. EXPERT OPINION: Encouraging results have been observed with immunotherapeutic strategies; some clinical trials are reaching phase III. Significant progress has been made in unraveling the molecular and genetic heterogeneity of GBM and its implications to disease prognosis. There is now consensus related to the critical need to incorporate tumor heterogeneity into the design of therapeutic approaches. Recent data also indicates that an efficacious treatment strategy will need to be combinatorial and personalized to the tumor genetic signature. PMID- 27411029 TI - Modulation of renal ischemia/reperfusion in rats by a combination of ischemic preconditioning and adipose-derived mesenchymal stem cells (ADMSCs). AB - The present study investigated the effects of combination of ischemic preconditioning (Ipre) and adipose-derived mesenchymal stem cells (ADMSCs) on renal ischemia-reperfusion (I-R) injury in rats. 90 male Sprague Dawley rats were divided into 5 equal groups; sham operated, control (45 min left renal ischemia), Ipre group as control group with 3 cycles of Ipre just before renal ischemia, ADMSCs-treated group (as control with ADMSCs 10(6) cells in 0.1 mL via penile vein 60 min before ischemia time), and Ipre + ADMSCs group as ADMCs group with 3 cycles of Ipre. Ipre and ADMSCs groups showed significant decrease in serum creatinine and blood urea nitrogen (BUN) and caspase-3 and CD45 expression in kidney and significant increase in HIF-1alpha, SDF-1alpha, CD31, and Ki67 expressions in kidney compared with the control group (p < 0.05). Moreover, the Ipre + ADMSCs group showed significant decrease in serum BUN and caspase-3 and CD45 expression in kidney with significant increase in HIF-1alpha, SDF-1alpha, CD31, and Ki67 expression in kidney compared with the Ipre and ADMCs groups (p < 0.05). We concluded that Ipre potentiates the renoprotective effect of ADMSCs against renal I/R injury probably by upregulation of HIF-1alpha, SDF-1alpha, CD31, and Ki67 and downregulation of caspase-3 and CD45. PMID- 27411030 TI - Epigenetic epidemiology as a tool to understand the role of immunity in chronic disease. PMID- 27411031 TI - Acute mesenteric ischemia in elderly patients. PMID- 27411033 TI - Anthropogenic pressure in a Portuguese river: Endocrine-disrupting compounds, trace elements and nutrients. AB - Natural organic compounds such as phytoestrogens and phytosterols found in various plants, as well as mycotoxins produced by fungi, can be found in aquatic environments. The aim of this study was to investigate the occurrence of three different classes of natural estrogenic compounds, i.e., phytoestrogens, phytosterols and mycotoxins, in estuarine water samples from the Ave River estuary. For that, water samples were collected at five sampling points distributed along the estuary at low tide, during 1 year, processed by solid phase extraction (SPE) and analyzed by gas chromatography coupled to mass spectrometry (GC-MS). To correlate the presence of phytoestrogens and phytosterols in the estuarine water, local flora was collected on riverside. Trace elements content and physicochemical parameters such as nutrients and dissolved oxygen were also determined seasonally at each sampling point, to give insights for the evaluation of water quality and anthropogenic pressure. Both phytoestrogens and phytosterols showed a seasonal variation, with the highest values observed in spring and summer and the lowest in winter. Daidzein (DAID) was found up to 404.0 ng L(-1) in spring and coumestrol (COUM) was found up to 165.0 ng L(-1) in summer. The mycotoxin deoxynivalenol (DON) was ubiquitously determined with values ranging from 59.5 to 642.4 ng L(-1). Nutrients and metals distribution and concentration varied among sampling stations and seasons. This study revealed for the first time the presence of mycotoxins, various classes of phytoestrogens and stigmasterol (STG) in estuarine water from the Ave River (Portugal), and the evaluation of the water quality confirmed that this estuary is still highly impacted by anthropogenic activities. PMID- 27411032 TI - In vitro bioacessibility and transport across Caco-2 monolayers of haloacetic acids in drinking water. AB - Water disinfection plays a crucial role in water safety but it is also a matter of concern as the use of disinfectants promotes the formation of disinfection by products (DBPs). Haloacetic acids (HAAs) are one of the major classes of DBPs since they are frequently found in treated water, are ubiquitous, pervasive and have high water solubility, so a great concern emerged about their formation, occurrence and toxicity. Exposure to HAAs is influenced by consumption patterns and diet of individuals thus their bioavailability is an important parameter to the overall toxicity. In the current study the bioacessibility of the most representative HAAs (chloroacetic acid - MCAA, bromoacetic acid - MBAA, dichloroacetic acid - DCAA, dibromoacetic acid - DBAA, and trichloroacetic acid - TCAA) after simulated in vitro digestion (SIVD) in tap water and transport across Caco-2 monolayers was evaluated. Compounds were monitored in 8 points throughout the digestion phases by an optimized LC-MS/MS methodology. MCAA and MBAA were not bioaccessible after SIVD whereas DCAA, DBAA and TCAA are highly bioaccessible (85 +/- 4%, 97 +/- 4% and 106 +/- 7% respectively). Concerning transport assays, DCAA and DBAA were highly permeable throughout the Caco-2 monolayer (apparent permeability and calculated fraction absorbed of 13.62 * 10(-6) cm/s and 90% for DCAA; and 8.82 * 10(-6) cm/s and 84% for DBAA), whereas TCAA showed no relevant permeability. The present results may contribute to efficient risk analysis studies concerning HAAs oral exposure from tap water taking into account the different biological behaviour of these chemically similar substances. PMID- 27411034 TI - Lipid Cross-Linking of Nanolipoprotein Particles Substantially Enhances Serum Stability and Cellular Uptake. AB - Nanolipoprotein particles (NLPs) consist of a discoidal phospholipid lipid bilayer confined by an apolipoprotein belt. NLPs are a promising platform for a variety of biomedical applications due to their biocompatibility, size, definable composition, and amphipathic characteristics. However, poor serum stability hampers the use of NLPs for in vivo applications such as drug formulation. In this study, NLP stability was enhanced upon the incorporation and subsequent UV mediated intermolecular cross-linking of photoactive DiynePC phospholipids in the lipid bilayer, forming cross-linked nanoparticles (X-NLPs). Both the concentration of DiynePC in the bilayer and UV exposure time significantly affected the resulting X-NLP stability in 100% serum, as assessed by size exclusion chromatography (SEC) of fluorescently labeled particles. Cross-linking did not significantly impact the size of X-NLPs as determined by dynamic light scattering and SEC. X-NLPs had essentially no degradation over 48 h in 100% serum, which is a drastic improvement compared to non-cross-linked NLPs (50% degradation by ~10 min). X-NLPs had greater uptake into the human ATCC 5637 bladder cancer cell line compared to non-cross-linked particles, indicating their potential utility for targeted drug delivery. X-NLPs also exhibited enhanced stability following intravenous administration in mice. These results collectively support the potential utility of X-NLPs for a variety of in vivo applications. PMID- 27411035 TI - Using ILD or ITD Cues for Sound Source Localization and Speech Understanding in a Complex Listening Environment by Listeners With Bilateral and With Hearing Preservation Cochlear Implants. AB - PURPOSE: To assess the role of interaural time differences and interaural level differences in (a) sound-source localization, and (b) speech understanding in a cocktail party listening environment for listeners with bilateral cochlear implants (CIs) and for listeners with hearing-preservation CIs. METHODS: Eleven bilateral listeners with MED-EL (Durham, NC) CIs and 8 listeners with hearing preservation CIs with symmetrical low frequency, acoustic hearing using the MED EL or Cochlear device were evaluated using 2 tests designed to task binaural hearing, localization, and a simulated cocktail party. Access to interaural cues for localization was constrained by the use of low-pass, high-pass, and wideband noise stimuli. RESULTS: Sound-source localization accuracy for listeners with bilateral CIs in response to the high-pass noise stimulus and sound-source localization accuracy for the listeners with hearing-preservation CIs in response to the low-pass noise stimulus did not differ significantly. Speech understanding in a cocktail party listening environment improved for all listeners when interaural cues, either interaural time difference or interaural level difference, were available. CONCLUSIONS: The findings of the current study indicate that similar degrees of benefit to sound-source localization and speech understanding in complex listening environments are possible with 2 very different rehabilitation strategies: the provision of bilateral CIs and the preservation of hearing. PMID- 27411037 TI - Key donor factors associated with graft loss among liver transplant recipients with human immunodeficiency virus. AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected liver transplant (LT) recipients have higher risk of graft loss than HIV-uninfected recipients. As the original donor risk index excluded HIV-positive patients, donor factors associated with graft loss in HIV-positive recipients are unknown. METHODS: Identifying all HIV-positive patients in the Scientific Registry of Transplant Recipients, supplemented by all HIV-infected patients in the solid organ transplantation in HIV: Multi-Site Study (HIV-TR), we evaluated donor factors associated with graft loss among HIV-positive recipients transplanted between March 2002 and August 2012. RESULTS: A total of 249 HIV-positive LT recipients were followed for median 2.4 (interquartile range [IQR]: 0.8-4.9) years. In univariate analysis, donor diabetes (HR=2.09; P=.002) and donor hypertension (HR=1.43; P=.048) were significantly associated with graft loss, and African American (AA) recipient:non-AA donor race mismatch (HR=1.60; P=.07), other cause of donor death compared to trauma (HR=2.02; P=.09), and donor age 30 years or older (HR=1.53; P=.05) were of borderline significance. In multivariate analysis, donor diabetes (HR=2.12; 95% CI: 1.33-3.38; P=.002) was the only significant predictor of graft loss. CONCLUSION: In HIV-positive LT recipients, risk of graft loss is strongly influenced by donor diabetes. This information may be useful to transplant physicians seeking to optimize overall graft survival in their HIV positive LT recipients. PMID- 27411036 TI - Reduction of friction by recombinant human proteoglycan 4 in IL-1alpha stimulated bovine cartilage explants. AB - A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interleukin 1alpha (IL-1alpha) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro. Cartilage explants, following a 7 day incubation with IL-1alpha, were tested in a disc-on disc configuration using either rhPRG4 or saline (PBS control) as a lubricant. Following mechanical testing, explants were studied immunohistochemically or underwent RNA extraction for real-time polymerase chain reaction (RT-PCR). We found that static coefficient of friction (COF) significantly decreased to 0.14 +/- 0.065 from 0.21 +/- 0.059 (p = 0.014) in IL-1alpha stimulated explants lubricated with rhPRG4, as compared to PBS. PRG4 expression was significantly up regulated from 30.8 +/- 19 copies in control explants lubricated with PBS to 3330 +/- 1760 copies in control explants lubricated with rhPRG4 (p < 0.001). Explants stimulated with IL-1alpha displayed no increase in PRG4 expression upon lubrication with rhPRG4, but with PBS as the lubricant, IL-1alpha stimulation significantly increased PRG4 expression compared to the control condition from 30.8 +/- 19 copies to 401 +/- 340 copies (p = 0.015). Overall, these data suggest that exogenous rhPRG4 may provide a therapeutic option for reducing friction in transient inflammatory conditions and increasing PRG4 expression. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:580-589, 2017. PMID- 27411038 TI - Is urinary neutrophil gelatinase-associated lipocalin able to predict acute kidney injury episodes in very low birth weight infants in clinical settings? AB - BACKGROUND: We evaluated the potential utility of elevated urinary neutrophil gelatinase-associated lipocalin (UNGAL) concentration as a screening test for early identification of acute kidney injury (AKI) in very low birth weight (VLBW) newborns. METHODS: Urine for UNGAL analysis was collected prospectively daily until 32 wk postmenstrual age in 91 VLBW newborns, yielding 2,899 specimens. UNGAL values > 50 ng/ml were considered elevated. AKI was defined as two or more consecutive elevations in s[Cr] above the 95th percentile adjusted for gestational age and chronological age within a 48 h period. We compared UNGAL values taken during the 5 d prior to AKI onset (pre-AKI) to values taken during non-AKI days. RESULTS: Overall, 15 episodes of AKI were identified in 13 infants. UNGAL was available in 44 pre-AKI days and 969 non-AKI days. UNGAL > 50 ng/ml occurred more often in pre-AKI days than in non-AKI days (risk ratio 3.48 (1.89, 6.40)). Positive and negative likelihood ratios were 1.92 (1.52, 2.41) and 0.52 (0.34, 0.78), respectively. CONCLUSION: Although UNGAL elevation > 50 ng/ml discriminates between pre-AKI and non-AKI days, high false positive and false negative rates limit utility as a screening test in VLBW newborns. PMID- 27411039 TI - Association of MBOAT7 gene variant with plasma ALT levels in children: the PANIC study. AB - BACKGROUND: We studied for the first time among children differences in plasma alanine aminotransferase (ALT) among genotypes of the rs641738 polymorphism in the MBOAT7 gene that has been associated with increased risk of nonalcoholic fatty liver disease among adults. We also investigated the associations of a genetic risk score combining information from the MBOAT7, PNPLA3, and TM6SF2 polymorphisms with plasma ALT. METHODS: We performed a 2-y follow-up study in 467 Caucasian children aged 6-9 y, genotyped the MBOAT7, PNPLA3, and TM6SF2 polymorphisms, calculated a genetic risk score from these polymorphisms (scored 0 3) and assessed plasma ALT. RESULTS: Children carrying the T allele of the MBOAT7 polymorphism had 7% higher plasma ALT at baseline (17.8 vs. 19.1 U/l, P = 0.022) and 10% higher plasma ALT at 2-y follow-up (18.0 vs. 19.7 U/l, P = 0.022) than the noncarriers. A higher genetic risk score was associated with higher plasma ALT at baseline (17.5, 18.5, 19.2, and 22.8 U/l, P = 0.008 for linear trend) and 2-y follow-up (18.2, 18.9, 18.9, and 32.8 U/l, P = 0.017 for linear trend). CONCLUSION: Children carrying the T allele of the MBOAT7 polymorphism had higher plasma ALT than the noncarriers. Children with the MBOAT7, PNPLA3, and TM6SF2 variants had the highest plasma ALT. PMID- 27411040 TI - Pinpointing a Mechanistic Switch Between Ketoreduction and "Ene" Reduction in Short-Chain Dehydrogenases/Reductases. AB - Three enzymes of the Mentha essential oil biosynthetic pathway are highly homologous, namely the ketoreductases (-)-menthone:(-)-menthol reductase and (-) menthone:(+)-neomenthol reductase, and the "ene" reductase isopiperitenone reductase. We identified a rare catalytic residue substitution in the last two, and performed comparative crystal structure analyses and residue-swapping mutagenesis to investigate whether this determines the reaction outcome. The result was a complete loss of native activity and a switch between ene reduction and ketoreduction. This suggests the importance of a catalytic glutamate vs. tyrosine residue in determining the outcome of the reduction of alpha,beta unsaturated alkenes, due to the substrate occupying different binding conformations, and possibly also to the relative acidities of the two residues. This simple switch in mechanism by a single amino acid substitution could potentially generate a large number of de novo ene reductases. PMID- 27411041 TI - Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas. AB - We determined whether the structural and functional integrity of amacrine cells (ACs), the largest cohort of neurons in the mammalian retina, are affected in glaucoma. Intraocular injection of microbeads was made in mouse eyes to elevate intraocular pressure as a model of experimental glaucoma. Specific immunocytochemical markers were used to identify AC and displaced (d)ACs subpopulations in both the inner nuclear and ganglion cell layers, respectively, and to distinguish them from retinal ganglion cells (RGCs). Calretinin- and gamma aminobutyric acid (GABA)-immunoreactive (IR) cells were highly vulnerable to glaucomatous damage, whereas choline acetyltransferase (ChAT)-positive and glycinergic AC subtypes were unaffected. The AC loss began 4 weeks after initial microbead injection, corresponding to the time course of RGC loss. Recordings of electroretinogram (ERG) oscillatory potentials and scotopic threshold responses, which reflect AC and RGC activity, were significantly attenuated in glaucomatous eyes following a time course that matched that of the AC and RGC loss. Moreover, we found that it was the ACs coupled to RGCs via gap junctions that were lost in glaucoma, whereas uncoupled ACs were largely unaffected. Our results suggest that AC loss in glaucoma occurs secondary to RGC death through the gap junction mediated bystander effect. J. Comp. Neurol., 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27411043 TI - Coming in postgraduate medicine. PMID- 27411044 TI - Problems solutions. PMID- 27411042 TI - Cost of Illness of Multiple Sclerosis - A Systematic Review. AB - BACKGROUND: Cost-of-illness (COI) studies of Multiple Sclerosis (MS) are vital components for describing the economic burden of MS, and are frequently used in model studies of interventions of MS. We conducted a systematic review of studies estimating the COI of MS, to compare costs between studies and examine cost drivers, emphasizing generalizability and methodological choices. MATERIAL AND METHOD: A literature search on studies published in English on COI of MS was performed in PubMed for the period January 1969 to January 2014, resulting in 1,326 publications. A mapping of studies using a bottom-up approach or top-down approach, respectively, was conducted for the 48 studies assessed as relevant. In a second analysis, the cost estimates were compared between the 29 studies that used a societal perspective on costs, human capital approach for indirect costs, presenting number of patients included, time-period studied, and year of price level used. RESULTS: The mapping showed that bottom-up studies and prevalence approaches were most common. The cost ratios between different severity levels within studies were relatively stable, to the ratio of 1 to 2 to 3 for disability level categories. Drugs were the main cost drivers for MS-patients with low disease severity, representing 29% to 82% of all costs in this patient group, while the main cost components for groups with more advanced MS symptoms were production losses due to MS and informal care, together representing 17% to 67% of costs in those groups. CONCLUSION: The bottom-up method and prevalence approach dominated in studies of COI of MS. Our findings show that there are difficulties in comparing absolute costs across studies, nevertheless, the relative costs expressed as cost ratios, comparing different severity levels, showed higher resemblance. Costs of drugs were main cost drivers for less severe MS and informal care and production losses for the most severe MS. PMID- 27411045 TI - What's happening in medicine. PMID- 27411046 TI - Washington background. PMID- 27411048 TI - Self-Test Sexuality and Sexual Health. PMID- 27411047 TI - Introduction. PMID- 27411051 TI - 1975 Interstate Postgraduate Medical Assembly Program. PMID- 27411049 TI - ReadySource on Sexuality and Sexual Health. PMID- 27411052 TI - Therapeutic Index To Advertisers. PMID- 27411053 TI - Validation of Reference Genes for Oral Cancer Detection Panels in a Prospective Blinded Cohort. AB - BACKGROUND: Reference genes are needed as internal controls to determine relative expression for clinical application of gene expression panels. Candidate constitutively expressed genes must be validated as suitable reference genes in each body fluid and disease entity. Prior studies have predominantly validated oral squamous cell carcinoma associated messenger RNAs (mRNAs) based on quantitative polymerase chain reaction (qPCR) quantification cycle (Cq) values without adjustment for housekeeping genes. METHODS: One hundred sixty eight patients had saliva collected before clinically driven biopsy of oral lesions suspicious for cancer. Seven potential housekeeping mRNAs and six pre-specified oral cancer associated mRNAs were measured with qPCR by personnel blinded to tissue diagnosis. Housekeeping gene stability was determined with the NormFinder program in a training set of 12 randomly selected cancer and 24 control patients. Genes with stability indices <0.02 were then tested in the validation set consisting of the remaining cancer and control patients and were further validated by the geNorm program. Cancer gene delta Cqs were compared in case and control patients after subtracting the geometric mean of the reference gene raw Cqs. RESULTS: B2M and UBC had stability indices >0.02 in the training set and were not further tested. MT-ATP6, RPL30, RPL37A, RPLP0 and RPS17 all had stability indices <0.02 in the training set and in the verification set. The geNorm M values were all <=1.10. All six pre-specified cancer genes (IL8, IL1, SAT, OAZ1, DUSP1 and S100P) were up-regulated in cancer versus control patients with from nearly twofold to over threefold higher levels (p<0.01 for all based on delta Cq values). CONCLUSIONS: Five reference genes are validated for use in oral cancer salivary gene expression panels. Six pre-specified oral carcinoma associated genes are demonstrated to be highly significantly up-regulated in cancer patients based on delta Cq values. These cancer and reference genes are suitable for inclusion in gene expression panels for research and clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01587573. PMID- 27411054 TI - Clinical and Histologic Features of Lichenoid Mucocutaneous Eruptions Due to Anti Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Immunotherapy. AB - Importance: Antagonist antibodies to programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have shown remarkable activity in multiple tumor types. Recent US Food and Drug Administration approval of such agents for advanced melanoma, non-small cell lung cancer, and renal cell carcinoma has hastened the need to better characterize their unique toxicity profiles. Objective: To provide a clinical and pathologic description of the lichenoid mucocutaneous adverse effects seen in patients receiving anti-PD-1/PD-L1 treatment. Design, Setting, and Participants: Patients with advanced cancer who were referred to dermatology at Yale-New Haven Hospital, a tertiary care hospital, after developing cutaneous adverse effects while receiving an anti-PD-1 or PD-L1 antibody therapy either as monotherapy or in combination with another agent were identified. Medical records from 2010 to 2015 and available skin biopsy specimens were retrospectively reviewed. Main Outcomes and Measures: Patient demographic characteristics, concurrent medications, therapeutic regimen, type of disease, previous oncologic therapies, clinical morphology of cutaneous lesions, treatment of rash, peripheral blood eosinophil count, tumor response, and skin histologic characteristics if biopsies were available. Results: Patients were 13 men and 7 women, with a mean (range) age of 64 (46-86) years. The majority of cases (16 [80%]) had a clinical morphology consisting of erythematous papules with scale in a variety of distributions. Biopsies were available from 17 patients; 16 (94%) showed features of lichenoid interface dermatitis. Eighteen patients were treated with topical corticosteroids, and only 1 patient required discontinuation of anti-PD-1/PD-L1 therapy. Only 4 of 20 patients (20%) developed peripheral eosinophilia. Sixteen patients (80%) were concurrently taking medications that have been previously reported to cause lichenoid drug eruptions. Conclusions and Relevance: Papular and nodular eruptions with scale, as well as mucosal erosions, with lichenoid features on histologic analysis were a distinct finding seen with anti-PD-1/PD-L1 therapies and were generally manageable with topical steroids. Concurrent medications may play a role in the development of this cutaneous adverse effect. PMID- 27411055 TI - A new gain-of-function mouse line to study the role of Wnt3a in development and disease. AB - Wnt/beta-catenin signals are important regulators of embryonic and adult stem cell self-renewal and differentiation and play causative roles in tumorigenesis. Purified recombinant Wnt3a protein, or Wnt3a-conditioned culture medium, has been widely used to study canonical Wnt signaling in vitro or ex vivo. To study the role of Wnt3a in embryogenesis and cancer models, we developed a Cre recombinase activatable Rosa26(Wnt3a) allele, in which a Wnt3a cDNA was inserted into the Rosa26 locus to allow for conditional, spatiotemporally defined expression of Wnt3a ligand for gain-of-function (GOF) studies in mice. To validate this reagent, we ectopically overexpressed Wnt3a in early embryonic progenitors using the T-Cre transgene. This resulted in up-regulated expression of a beta catenin/Tcf-Lef reporter and of the universal Wnt/beta-catenin pathway target genes, Axin2 and Sp5. Importantly, T-Cre; Rosa26(Wnt3a) mutants have expanded presomitic mesoderm (PSM) and compromised somitogenesis and closely resemble previously studied T-Cre; Ctnnb1(ex3) (beta-catenin(GOF) ) mutants. These data indicate that the exogenously expressed Wnt3a stimulates the Wnt/beta-catenin signaling pathway, as expected. The Rosa26(Wnt3a) mouse line should prove to be an invaluable tool to study the function of Wnt3a in vivo. PMID- 27411056 TI - Errors in the scoring and reporting of cognitive screening instruments administered in primary care. AB - AIM: To measure the frequency of scoring and reporting errors in cognitive screening instruments administered in the primary care setting in consecutive referrals to a dedicated secondary care memory clinic. METHODS: Using a simple ad hoc classification, referral letters from primary care mentioning cognitive screening instrument use were classified as: unequivocal, incorrect/ambiguous or incomplete. RESULTS: Overall, reported test scores were either ambiguous/incorrect or incomplete in 23% of cases, with higher individual frequencies for two screening instruments recommended for use in primary care, the Six-item Cognitive Impairment Test (26%) and the General Practitioner Assessment of Cognition (32%). CONCLUSION: Errors are not infrequent in the scoring and reporting of cognitive screening instruments administered in primary care. More training in their correct use and scoring is required. PMID- 27411057 TI - In planta Transformed Cumin (Cuminum cyminum L.) Plants, Overexpressing the SbNHX1 Gene Showed Enhanced Salt Endurance. AB - Cumin is an annual, herbaceous, medicinal, aromatic, spice glycophyte that contains diverse applications as a food and flavoring additive, and therapeutic agents. An efficient, less time consuming, Agrobacterium-mediated, a tissue culture-independent in planta genetic transformation method was established for the first time using cumin seeds. The SbNHX1 gene, cloned from an extreme halophyte Salicornia brachiata was transformed in cumin using optimized in planta transformation method. The SbNHX1 gene encodes a vacuolar Na+/H+ antiporter and is involved in the compartmentalization of excess Na+ ions into the vacuole and maintenance of ion homeostasis Transgenic cumin plants were confirmed by PCR using gene (SbNHX1, uidA and hptII) specific primers. The single gene integration event and overexpression of the gene were confirmed by Southern hybridization and competitive RT-PCR, respectively. Transgenic lines L3 and L13 showed high expression of the SbNHX1 gene compared to L6 whereas moderate expression was detected in L5 and L10 transgenic lines. Transgenic lines (L3, L5, L10 and L13), overexpressing the SbNHX1 gene, showed higher photosynthetic pigments (chlorophyll a, b and carotenoid), and lower electrolytic leakage, lipid peroxidation (MDA content) and proline content as compared to wild type plants under salinity stress. Though transgenic lines were also affected by salinity stress but performed better compared to WT plants. The ectopic expression of the SbNHX1 gene confirmed enhanced salinity stress tolerance in cumin as compared to wild type plants under stress condition. The present study is the first report of engineering salt tolerance in cumin, so far and the plant may be utilized for the cultivation in saline areas. PMID- 27411059 TI - A Cyanine Dye Encapsulated Porous Fibrous Mat for Naked-Eye Ammonia Sensing. AB - Electrospun ultrathin fiber-based sensors are desirable because of their practicality and sensitivity. Ammonia-detection systems are in high demand in different areas, including the industrial and agricultural fields. However, current technologies rely on large and complex instruments that restrict their actual utilization. Herein, we report a flexible naked-eye ammonia sensor, the polylactic acid-cyanine (PLA-Cy) fibrous mat, which was fabricated by blending a carboxyl-functionalized cyanine dye (D1) into electospun PLA porous fibers. The sensing mat was shown to undergo a naked-eye-detectable color change from white to blue upon exposure to ammonia vapor. The mat showed high selectivity to ammonia gas with a detection limit of 3.3 ppm. Aggregated D1 was first encapsulated by PLA and was then ionized by NH3 . These mechanisms were examined by photophysical studies and scanning electron microscopy. The aggregation deaggregation process of D1 in the PLA-Cy fibrous mat led to the color change. This work provides a facile method for the naked-eye detection of ammonia and a novel strategy for the use of organic dyes in ammonia sensing. PMID- 27411058 TI - Preventing Data Ambiguity in Infectious Diseases with Four-Dimensional and Personalized Evaluations. AB - BACKGROUND: Diagnostic errors can occur, in infectious diseases, when anti microbial immune responses involve several temporal scales. When responses span from nanosecond to week and larger temporal scales, any pre-selected temporal scale is likely to miss some (faster or slower) responses. Hoping to prevent diagnostic errors, a pilot study was conducted to evaluate a four-dimensional (4D) method that captures the complexity and dynamics of infectious diseases. METHODS: Leukocyte-microbial-temporal data were explored in canine and human (bacterial and/or viral) infections, with: (i) a non-structured approach, which measures leukocytes or microbes in isolation; and (ii) a structured method that assesses numerous combinations of interacting variables. Four alternatives of the structured method were tested: (i) a noise-reduction oriented version, which generates a single (one data point-wide) line of observations; (ii) a version that measures complex, three-dimensional (3D) data interactions; (iii) a non numerical version that displays temporal data directionality (arrows that connect pairs of consecutive observations); and (iv) a full 4D (single line-, complexity , directionality-based) version. RESULTS: In all studies, the non-structured approach revealed non-interpretable (ambiguous) data: observations numerically similar expressed different biological conditions, such as recovery and lack of recovery from infections. Ambiguity was also found when the data were structured as single lines. In contrast, two or more data subsets were distinguished and ambiguity was avoided when the data were structured as complex, 3D, single lines and, in addition, temporal data directionality was determined. The 4D method detected, even within one day, changes in immune profiles that occurred after antibiotics were prescribed. CONCLUSIONS: Infectious disease data may be ambiguous. Four-dimensional methods may prevent ambiguity, providing earlier, in vivo, dynamic, complex, and personalized information that facilitates both diagnostics and selection or evaluation of anti-microbial therapies. PMID- 27411060 TI - The End of the Cold Loneliness: 3D Comparison between Doto antarctica and a New Sympatric Species of Doto (Heterobranchia: Nudibranchia). AB - Although several studies are devoted to determining the diversity of Antarctic heterobranch sea slugs, new species are still being discovered. Among nudibranchs, Doto antarctica Eliot, 1907 is the single species of this genus described from Antarctica hitherto, the type locality being the Ross Sea. Doto antarctica was described mainly using external features. During our Antarctic research on marine benthic invertebrates, we found D. antarctica in the Weddell Sea and Bouvet Island, suggesting a circumpolar distribution. Species affiliation is herein supported by molecular analyses using cytochrome c oxidase subunit I, 16S rRNA, and histone H3 markers. We redescribe D. antarctica using histology, micro-computed tomography (micro-CT), and 3D-reconstruction of the internal organs. Moreover, we describe a new, sympatric species, namely D. carinova Moles, Avila & Wagele n. sp., and provide an anatomical comparison between the two Antarctic Doto species. Egg masses in both species are also described here for the first time. We demonstrate that micro-CT is a useful tool for non-destructive anatomical description of valuable specimens. Furthermore, our high resolution micro-CT data reveal that the central nervous system of both Doto species possesses numerous accessory giant cells, suggested to be neurons herein. In addition, the phylogenetic tree of all Doto species sequenced to date suggests a scenario for the evolution of the reproductive system in this genus: bursa copulatrix seems to have been reduced and the acquisition of a distal connection of the oviduct to the nidamental glands is a synapomorphy of the Antarctic Doto species. Overall, the combination of thorough morphological and anatomical description and molecular analyses provides a comprehensive means to characterize and delineate species, thus suggesting evolutionary scenarios. PMID- 27411062 TI - Resource predictability and specialization in avian malaria parasites. AB - We tested the hypothesis that avian haemosporidian (malaria) parasites specialize on hosts that can be characterized as predictable resources at a site in Amazonian Ecuador. We incorporated host phylogenetic relationship and relative abundance in assessing parasite specialization, and we examined associations between parasite specialization and three host characteristics - abundance, mass and longevity - using quantile regression, phylogenetic logistic regression and t tests. Hosts of specialist malaria parasite lineages were on average more abundant than hosts of generalist parasite lineages, but the relationship between host abundance and parasite specialization was not consistent across analyses. We also found support for a positive association between parasite specialization and host longevity, but this also was not consistent across analyses. Nonetheless, our findings suggest that the predictability of a host resource may play a role in the evolution of specialization. However, we also discuss two alternative explanations to the resource predictability hypothesis for specialization: (i) that interspecific interactions among the parasites themselves might constrain some parasites to a specialist strategy, and (ii) that frequent encounters with multiple host species, mediated by blood-sucking insects, might promote generalization within this system. PMID- 27411061 TI - In Vivo Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model. AB - Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNgamma) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNgamma responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs. PMID- 27411064 TI - Multicenter Evaluation of Prehospital Opioid Pain Management in Injured Children. AB - BACKGROUND: The National Association of Emergency Medical Services Physicians' (NAEMSP) Position Statement on Prehospital Pain Management and the joint National Highway Traffic Safety Administration (NHTSA) and Emergency Medical Services for Children (EMSC) Evidence-based Guideline for Prehospital Analgesia in Trauma aim to improve the recognition, assessment, and treatment of prehospital pain. The impact of implementation of these guidelines on pain management in children by emergency medical services (EMS) agencies has not been assessed. OBJECTIVE: Determine the change in frequency of documented pain severity assessment and opiate administration among injured pediatric patients in three EMS agencies after adoption of best practice recommendations. METHODS: This is a retrospective study of children <18 years of age with a prehospital injury-related primary impression from three EMS agencies. Each agency independently implemented pain protocol changes which included adding the use of age-appropriate pain scales, decreasing the minimum age for opiate administration, and updating fentanyl dosing. We abstracted data from prehospital electronic patient records before and after changes to the pain management protocols. The primary outcomes were the frequency of administration of opioid analgesia and documentation of pain severity assessment as recorded in the prehospital patient care record. RESULTS: A total of 3,597 injured children were transported prior to pain protocol changes and 3,743 children after changes. Opiate administration to eligible patients across study sites regardless of documentation of pain severity was 156/3,089 (5%) before protocol changes and 175/3,509 (5%) after (p = 0.97). Prior to protocol changes, 580 (18%) children had documented pain assessments and 430 (74%) had moderate-to-severe pain. After protocol changes, 644 (18%) patients had pain severity documented with 464 (72%) in moderate-to-severe pain. For all study agencies, pain severity was documented in 13%, 19%, and 22% of patient records both before and after protocol changes. There was a difference in intranasal fentanyl administration rates before (27%) and after (17%) protocol changes (p = 0.02). CONCLUSION: The proportion of injured children who receive prehospital opioid analgesia remains suboptimal despite implementation of best practice recommendations. Frequency of pain severity assessment of injured children is low. Intranasal fentanyl administration may be an underutilized modality of prehospital opiate administration. PMID- 27411063 TI - Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein. AB - Numerous broadly neutralizing antibodies (Abs) target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes). Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope targeting Abs (QtAbs), we previously used HIV virus-like particles (VLPs) to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection. PMID- 27411065 TI - Reproductive biology of Thamnodynastes hypoconia (Serpentes: Dipsadidae) in Brazilian subtemperate wetlands. AB - This study aimed to describe the reproductive biology of populations of Thamnodynastes hypoconia in subtemperate wetlands based on macroscopic analyses of their gonads. We analyzed 101 specimens from the southernmost regions of Brazil. The males had a greater snout-vent length, but the females reached sexual maturity with a greater body size. The reproductive cycle of the females was seasonal, with secondary vitellogenesis occurring between the winter and spring (May-October). Based on macroscopic analysis of gonads, data suggests that males have a continuous reproductive cycle. Parturition occurs between the late summer and early fall (January-April). The clutch size ranged between 4 and 16 embryos and showed no relationship with the female's body size. The recorded reproductive frequency of T. hypoconia is low (38 %) compared to other phylogenetically related species. Conversely, the studied populations appear to have a high reproductive success because it is an abundant species in the study site. PMID- 27411066 TI - Description of the last instar larva and new contributions to the knowledge of the pupa of Dasyhelea mediomunda Minaya (Diptera, Culicomorpha, Ceratopogonidae). AB - The fourth instar larva of Dasyhelea mediomunda Minaya is described for the first time and a complete description of the pupa is provided, through use of phase contrast microscope and scanning electron microscope. Studied specimens were collected in a pond connected to a small wetland "mallin" on the Patagonian steppe, Chubut province, Argentina. PMID- 27411067 TI - Bioactivities of the ethanol extract from Ageratum fastigiatum branches: antioxidant, antinociceptive and anti-inflammatory. AB - The present study was designed to investigate the antioxidant, antinociceptive and anti-inflammatory activities of the ethanol extract from Ageratum fastigiatum branches. Phytochemical screening and total phenol and flavonoid contents were determined. The antioxidant activity was assessed by 2,2-diphenyl-1 pycrilhydrazin (DPPH) and iron reducing power methods. The antinociceptive effect was evaluated using the acetic acid-induced writhing, formalin, hot plate and tail immersion assays; while the carrageenan-induced paw edema and pleurisy tests were performed to examine the anti-inflammatory activity against acute inflammation. The extract revealed the presence of flavonoids, tannins, coumarins, terpenes, sterols and saponins. Expressive levels of total phenols and flavonoids and a promising antioxidant effect were quantified. At the doses of 50, 100 and 200 mg/kg, the extract inhibited the writhing, reduced both phases of paw licking time and increased the reaction time on the hot plate. In the tail immersion test, the extract (50, 100 and 200 mg/kg) caused a significant inhibition of pain. In these doses, the paw edema, exudate volume and leucocyte mobilization were significantly reduced. These results suggest that A. fastigiatum can be an active source of substances with antioxidant, antinociceptive and anti-inflammatory activities, adding scientific support to the appropriate use in the Brazilian folk medicine. PMID- 27411068 TI - Biological variables of Hypostomus francisci (Siluriformes: Loricariidae) from Itapecerica River, Minas Gerais State, Brazil. AB - Herein we determine for the first time the reproduction parameters and population structure of Hypostomus francisci in the Itapecerica River, Sao Francisco Basin. A total of 250 specimens was captured quarterly between March 2010 and February 2012. Body weight, total length and weight of the gonads were obtained in the laboratory. Gonad samples were submitted to histological and histochemical techniques. Females with spawning capable ovaries were used to determine the fecundity and relative fecundity. Sex ratio with 1:1.01 (female:male) was observed. Males were more numerous than females for individuals smaller than 170 mm, however the number of females was significantly greater for specimens larger than 330 mm. The length-weight relationship estimated for H. francisci indicates negative-allometric growth. Females spawning capable were observed mostly in November-December-January. Two cohorts of oocytes at a determined time evidencing the development type group-synchronic. The eggs reaching 3.4 mm and the fecundity ranged from 312-1,460 oocytes with an average of 585.81 +/- 337.43 oocytes per female. The reproductive parameters and population structure of H. francisci from Itapecerica River suggested that this species showed singular reproductive tactics among congeners. PMID- 27411069 TI - Reproductive phenology of the American Bullfrog in subtropical Brazil: photoperiod as a main determinant of seasonal activity. AB - The North American bullfrog Lithobates catesbeianus continues to invade ecosystems worldwide, potentially causing population declines and even extinctions. Within its native distribution, bullfrogs show prolonged reproductive seasons and high fertility. However, data on breeding biology of bullfrogs ex-situ in invaded localities mainly comes from anecdotal reports. Understanding how invasive species are adjusting their life histories to new colonized environments is important for conservation purposes. Here we describe temporal and spatial abundance, calling activity, spawning and tadpole distribution of bullfrogs in southern Brazil. Eighteen samplings occurred during one year. The abundance of individuals was positively related to longer photoperiods and higher temperatures. Reproductive activity was also positively associated with longer photoperiods. Calling sites, spawning and tadpoles were associated with microhabitats presenting hydrophytes, which may provide shelter and thermal stability to bullfrogs. The reproductive seasonal activity of bullfrogs can be highly variable across its growing geographical range, but in subtropical Brazil it is associated with photoperiod, a highly predictable abiotic determinant. In our study area, bullfrogs presented a breeding season twice as long as that observed in some native localities. We suggest that management strategies directed to bullfrog populations must consider the habitat structures and seasonal regimes determined by each invaded environment. PMID- 27411070 TI - The gastroprotective effect of Memora nodosa roots against experimental gastric ulcer in mice. AB - Memora nodosa is popularly known as "caroba" and widely found in the Cerrado regions of Brazil. In traditional medicine, the leaves and stems are used for the healing of external ulcer and the roots for abdominal pain. This study investigated the effect of ethanolic roots extract of Memora nodosa (EMN) on the gastric mucosa of mice. In the indomethacin induced gastric ulcer model, the treatments of the animals with EMN at doses of 100, 300 and 1000 mg/kg, p.o., markedly reduced the index of lesions. In the gastric ulcer models induced by ethanol and cold restraint-stress the previous treatment with EMN at dose of 300 mg/kg showed 69% and 43% of protection, respectively. Seven days after food restriction, the animals treated with EMN (300 mg/kg p.o.) showed reduction in the index of lesion by 65% as compared to control group. The intraduodenal administration of EMN (300 mg/kg) did not alter the gastric acid secretion parameters. The treatment with EMN (300 mg/kg p.o.) did not alter glutathione levels (GSH), but showed an increase of adhered gastric mucus as compared to the control group with lesion. These results showed that EMN has gastroprotective activity probably due with an increase of adhered gastric mucus. PMID- 27411071 TI - Correlation between infection rate of triatominies and Chagas Disease in Southwest of Bahia, Brazil: a warning sign? AB - Chagas disease, caused by the Trypanosoma cruzi, has a wide distribution in South America, and its main method of control is the elimination of triatomines. It is presented here the geographic distribution and the rate of natural infection by T. cruzi of triatomines collected and evaluated from 2008 to 2013 in southwest of Bahia. Triatomines were captured in the intradomiciliary and peridomiciliary areas of five cities located in the southwest of Bahia state, identified, and analyzed for the presence of trypanosomatids in their feces. During the study period the number of patients suspected for acute Chagas disease was recovered from the Notifiable Diseases Information System (SINAN). 8966 triatomines were captured and identified as belonging to eight species. Twenty-six presented themselves infected, being Triatoma sordida the most abundant and with the highest percentage of infection by T. cruzi. Tremedal was the city with the highest number of cases of acute Chagas' disease reported to SINAN. All cities showed triatomines infected with T. cruzi, so there is considerable risk of vectorial transmission of Chagas disease in the southwestern Bahia state, evidencing the need for vector transmission control programs and preventive surveillance measures. PMID- 27411072 TI - Amyloid-beta peptide absence in short term effects on kinase activity of energy metabolism in mice hippocampus and cerebral cortex. AB - Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-beta or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol. In the fourteenth day, kinases activities were performed. Amyloid-beta did not change the kinases activity in the hippocampus and cerebral cortex of mice. However, free meloxicam decrease the creatine kinase activity in mitochondrial-rich fraction in the group induced by amyloid-beta, but for the cytosolic fraction, it has raised in the activity of pyruvate kinase activity in cerebral cortex. Further, meloxicam-loaded nanocapsules administration reduced adenylate kinase activity in the hippocampus of mice injected by amyloid-beta. In conclusion we observed absence in short-term effects in kinases activities of energy metabolism in mice hippocampus and cerebral cortex using amyloid-beta peptide model. These findings established the foundation to further study the kinases in phosphoryltransfer network changes observed in the brains of patients post-mortem with Alzheimer's disease. PMID- 27411073 TI - "It wasn't a disaster or anything": Parents' experiences of their child's uncertain chromosomal microarray result. AB - Chromosomal microarray is an increasingly utilized diagnostic test, particularly in the pediatric setting. However, the clinical significance of copy number variants detected by this technology is not always understood, creating uncertainties in interpreting and communicating results. The aim of this study was to explore parents' experiences of an uncertain microarray result for their child. This research utilized a qualitative approach with a phenomenological methodology. Semi-structured interviews were conducted with nine parents of eight children who received an uncertain microarray result for their child, either a 16p11.2 microdeletion or 15q13.3 microdeletion. Interviews were transcribed verbatim and thematic analysis was used to identify themes within the data. Participants were unprepared for the abnormal test result. They had a complex perception of the extent of their child's condition and a mixed understanding of the clinical relevance of the result, but were accepting of the limitations of medical knowledge, and appeared to have adapted to the result. The test result was empowering for parents in terms of access to medical and educational services; however, they articulated significant unmet support needs. Participants expressed hope for the future, in particular that more information would become available over time. This research has demonstrated that parents of children who have an uncertain microarray result appeared to adapt to uncertainty and limited availability of information and valued honesty and empathic ongoing support from health professionals. Genetic health professionals are well positioned to provide such support and aid patients' and families' adaptation to their situation as well as promote empowerment. (c) 2016 Wiley Periodicals, Inc. PMID- 27411074 TI - Lone-pair-pi interactions: analysis of the physical origin and biological implications. AB - Lone-pair-pi (lp-pi) interactions have been suggested to stabilize DNA and protein structures, and to participate in the formation of DNA-protein complexes. To elucidate their physical origin, we have carried out a theoretical multi approach analysis of two biologically relevant model systems, water-indole and water-uracil complexes, which we compared with the structurally similar chloride tetracyanobenzene (TCB) complex previously shown to contain a strong charge transfer (CT) binding component. We demonstrate that the CT component in lp-pi interactions between water and indole/uracil is significantly smaller than that stabilizing the Cl(-)-TCB reference system. The strong lp(Cl(-))-pi(TCB) orbital interaction is characterized by a small energy gap and an efficient lp-pi* overlap. In contrast, in lp-pi interactions between water and indole or uracil, the corresponding energy gap is larger and the overlap less efficient. As a result, water-uracil and water-indole interactions are weak forces composed by smaller contributions from all energy components: electrostatics, polarization, dispersion, and charge transfer. In addition, indole exhibits a negative electrostatic potential at its pi-face, making lp-pi interactions less favorable than O-Hpi hydrogen bonding. Consequently, some of the water-tryptophan contacts observed in X-ray structures of proteins and previously interpreted as lp-pi interactions [Luisi, et al., Proteins, 2004, 57, 1-8], might in fact arise from O Hpi hydrogen bonding. PMID- 27411075 TI - Can supplemental nitrate in cured meats be used as a means of increasing residual and dietary nitrate and subsequent potential for physiological nitric oxide without affecting product properties? AB - The effects of formulated sodium nitrate plus supplemental nitrate (SN) from celery juice powder on residual nitrite, residual nitrate, rancidity, microbial growth, color, sensory properties, and proximate composition of frankfurters, cotto salami and boneless ham during storage (1 degrees C) were studied. The products were assigned one of two treatments, which were each replicated twice: control (156ppm sodium nitrite) or SN (156ppm sodium nitrite and 1718ppm sodium nitrate in combination with 2% VegStable 502). Sensory parameters and proximate composition were measured once for each replication. All other analytical measurements were conducted at regular intervals for 97-98days. The SN showed no increase in residual nitrite compared to the control. No changes (P>0.05) were observed in residual nitrate during storage for any of the products. The results showed that addition of SN did not significantly alter most physical, chemical or microbial properties of cured meat products during refrigerated storage, but some product dependent sensory effects were observed. PMID- 27411076 TI - [Diagnosis and Treatment of Diaphragmatic Dysfunction]. AB - There are many reasons for an impairment of the diaphragmatic function potentially affecting all components of the respiratory pump. Particularly, diagnosis and treatment of unilateral and bilateral phrenic nerve paralysis are challenging. Neuromuscular disorders, trauma, iatrogenic conditions, tumor compression, but also infectious and inflammatory conditions in addition to neuralgic amyotrophy and idiopathic phrenic nerve paralysis are reasons for phrenic nerve paralysis. Primarily, diagnostic procedures include the anamnesis, physical examination, blood gas analysis, lung function testing and the diagnosis of the underlying disease. In addition, specific respiratory muscle testing and respiratory imaging are available today. Current established treatment options include respiratory muscle training, long-term non-invasive ventilation and surgical diaphragm plication in selected patients. PMID- 27411077 TI - An updated systematic review and meta-analysis on the association between Helicobacter pylori infection and iron deficiency anemia. AB - BACKGROUND: We conducted an updated systematic review and meta-analysis to examine the prevalence of depleted iron stores among persons infected with Helicobacter pylori compared to uninfected ones. We also assessed the impact of anti-H. pylori eradication therapy plus iron therapy on ferritin and hemoglobin levels compared to iron therapy alone. METHODS: A literature search was conducted using the databases Medline, the Cochrane Library, Cochrane Central Register of Controlled Trials, EMBASE, and the Science Citation Index Expanded. Observational studies with methodological quality score of 13 (median score) and above, on a scale of 0-16, and all randomized controlled trials (RCTs) were eligible for the meta-analyses. Pooled point estimates and 95% confidence intervals (CI) were obtained using the random effects model. RESULTS: Compared to uninfected persons, H. pylori-infected individuals showed increased likelihood of iron deficiency anemia (14 observational studies); pooled OR 1.72 (95% CI 1.23-2.42); iron deficiency (pooled OR 1.33; 95% CI 1.15-1.54; 30 studies); and anemia (pooled OR 1.15; 95% CI 1.00-1.32; 23 studies). Meta-analyses of seven RCTs showed increased ferritin, standardized mean difference (SMD) 0.53 (95% 0.21-0.85), but not hemoglobin, SMD 0.36 (95% -0.07 to 0.78), Pv=.1, following anti-H. pylori eradication therapy plus iron therapy as compared with iron therapy alone. Significant heterogeneity was found among studies, as well as evidence of publication bias. CONCLUSIONS: Current evidence indicates increased likelihood of depleted iron stores in relation to H. pylori infection. H. pylori eradication therapy, added to iron therapy, might be beneficial in increasing ferritin and hemoglobin levels. PMID- 27411078 TI - A review of endoscopic balloon dilatation techniques for treating Crohn's strictures: time to standardise therapy. AB - INTRODUCTION: Endoscopic balloon dilatation (EBD) is a recognised treatment for symptomatic Crohn's disease strictures. Over 3000 procedure are reported in the literature and yet the long term benefits are unclear. This is largely because of different populations, study designs, techniques, types of strictures, the outcome measures used and follow-up periods. AREAS COVERED: We summarised the techniques reported in the literature based on a systematic review and key factors that may influence outcome: pre-intervention imaging, stricture length and type, balloon size in relation to intestinal lumen diameter, duration of dilatation, frequency of repeat dilatation and instructions on follow-up. Expert commentary: We noted that shorter, non-ulcerated and anastomotic strictures fare better and 2 mins dilatation duration was the commonest technique used without an increased risk of complications. The findings were translated into a standardised protocol and a management pathway to guide clinicians on the therapeutic strategy for Crohn's strictures. To resolve the uncertainty about long-term benefits, future studies should adopt a replicable standardised EBD technique, define degree of fibrosis to decide therapy accordingly, compare it to alternative interventions (strictureplasty or stents) within a randomised controlled trial and apply a validated outcome measure to include intestinal damage and quality of life. PMID- 27411079 TI - Special Section Guest Editorial: Polarized Light for Biomedical Applications. PMID- 27411080 TI - Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy. AB - The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies. PMID- 27411081 TI - Positioning newborns on their back or right side for umbilical venous catheter insertion. AB - AIM: Newborns are placed supine for umbilical venous catheter insertion, and catheter tip position is confirmed with X-ray. Umbilical venous catheters are considered correctly positioned when the tip is in the inferior vena cava; however, frequently, the catheter tip enters the portal venous circulation. We wished to determine whether placing infants on their right side, rather than on the back, for umbilical venous catheter insertion results in more correctly placed catheters. METHODS: Newborns were randomised to be placed on their back, or turned onto their right side for catheter insertion. Primary outcome was correct catheter tip position on X-ray (visible in the midline at diaphragm level). RESULTS: Umbilical venous catheter insertion was successful in all infants enrolled. There was no difference in the proportion of correctly positioned catheters between the groups [back 23/44 (52%) versus right side 27/44 (61%), p = 0.389]. More infants randomised to back had the catheter tip in the portal circulation [back 13/44 (30%) versus right side 5/44 (11%), p = 0.034]. CONCLUSION: Positioning newborn infants on their right side did not result in more correctly placed umbilical venous catheters. The procedure was well tolerated and reduced the rate of tip insertion into the portal venous circulation. PMID- 27411082 TI - Acute cellular rejection and HLA mismatch in heart transplantation: insights from a developing country. AB - The notable evolution of heart transplant (HTX) has paralleled the capacity of diagnosing rejection and, consequently, initiating timely treatment. Acute cellular rejection, diagnosed by endomyocardial biopsy, is the most frequent in the first 6 months after HTX. HLA matching is not routinely performed in HTX due to the absence of consensus regarding its usefulness. However, the use of HLA typing might be underscored if it could predict an increased risk of rejection. Therefore, the aim of this study was to evaluate, at a public cardiology center in Brazil, the association between HLA mismatches and the incidence of acute cellular rejection in the first 6 months after HTX. Data were obtained from hospital records and from the National Transplant System. Overall, there was no association between the number of HLA mismatches and the frequency of acute cellular rejection, but there was a tendency toward a higher incidence of rejection with HLA-DR incompatibility. PMID- 27411083 TI - Organotrisulfide: A High Capacity Cathode Material for Rechargeable Lithium Batteries. AB - An organotrisulfide (RSSSR, R is an organic group) has three sulfur atoms which could be involved in multi-electron reduction reactions; therefore it is a promising electrode material for batteries. Herein, we use dimethyl trisulfide (DMTS) as a model compound to study its redox reactions in rechargeable lithium batteries. With the aid of XRD, XPS, and GC-MS analysis, we confirm DMTS could undergo almost a 4 e(-) reduction process in a complete discharge to 1.0 V. The discharge products are primarily LiSCH3 and Li2 S. The lithium cell with DMTS catholyte delivers an initial specific capacity of 720 mAh g(-1) DMTS and retains 82 % of the capacity over 50 cycles at C/10 rate. When the electrolyte/DMTS ratio is 3:1 mL g(-1) , the reversible specific energy for the cell including electrolyte can be 229 Wh kg(-1) . This study shows organotrisulfide is a promising high-capacity cathode material for high-energy rechargeable lithium batteries. PMID- 27411084 TI - Does the Dirac cone of germanene exist on metal substrates? AB - Germanene, a germanium analogue of graphene and silicene, has been synthesized on metal substrates. It is predicted that the intrinsic germanene has a Dirac cone in its band structure, just like graphene and silicene. Using first-principles calculations, we investigate the geometrical structures and electronic properties of germanene on the Ag, Au, Cu, Al, Pt and Ir substrates. The Dirac cone of germanene is destroyed on the Al, Pt and Ir substrates but preserved on the Ag and Au substrates with a slight band hybridization. The upper part of the Dirac cone is destroyed for germanene on the Cu substrate while the lower part remains preserved. By contrast, the Dirac cone is always destroyed for silicene on these metal substrates because of a strong band hybridization. Our study suggests that it is possible to extract the intrinsic properties of germanene on the Ag and Au substrates although it appears impossible for silicene on these two substrates. PMID- 27411085 TI - Chemical Characterization and Cytotoxic Activity of Blueberry Extracts (cv. Misty) Cultivated in Brazil. AB - Vaccinium corymbosum (L.) varieties cultivation is relatively recent in Brazil, but its production has been intensified given its good adaptability to the Southern Brazil climate. Blueberries are a rich source of phenolic compounds and contain significant levels of anthocyanins, flavonols, chlorogenic acids, and procyanidins, which lead to different biological activities. Chemical identification of skin and whole hydroalcoholic blueberry extracts (ExtSB and ExtWB) revealed the presence of anthocyanins concentrated in the skin and others chemicals compounds as quercetin glycosides, proanthocyanins dimers, citric, and chlorogenic acid in the pulp. Selectivity for tumor cell lines (Hep-2, HeLa, HT 29) using ExtSB and ExtWB extracts was observed through MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after 24 h of treatment when compared to nontumor cells (MRC-5). Morphological changes and late stages of apoptotic and necrosis process were seen in HT-29 cell line after ExtWB treatment, compared to nontumor cell line MRC-5. These results are in agreement with other studies that indicate the activity of compounds such as anthocyanins and other molecules found in Southern Highbush blueberry variety, attributed to promote beneficial effects on health that may respond as cytotoxic natural agent and contribute to cancer treatment. PMID- 27411087 TI - Click Chemistry Route to the Synthesis of Unusual Amino Acids, Peptides, Triazole Fused Heterocycles and Pseudodisaccharides. AB - Conjugation of different molecular species using copper(I)-catalyzed click reaction between azides and terminal alkynes is among the best available methods to prepare multifunctional compounds. The effectiveness of this method has provided wider acceptance to the concept of click chemistry, which is now widely employed to synthesize densely functionalized organic molecules. This article summarizes the contributions from our group in the development of new methods for the synthesis of functional molecules using copper(I)-catalyzed click reactions. We have developed very efficient methods for the synthesis of peptides and amino acids conjugated with carbohydrates, thymidine and ferrocene. We have also developed an efficient strategy to synthesize triazole-fused heterocycles from primary amines, amino alochols and diols. Finally, an interesting method for the synthesis of pseudodisaccharides linked through triazoles, starting from carbohydrate-derived donor-acceptor cyclopropanes is discussed. PMID- 27411086 TI - Epidemiology of Substance Use among Forced Migrants: A Global Systematic Review. AB - INTRODUCTION: Forced migration is occurring at unprecedented levels. Forced migrants may be at risk for substance use for reasons including coping with traumatic experiences, co-morbid mental health disorders, acculturation challenges and social and economic inequality. This paper aimed to systematically review the literature examining substance use among forced migrants, and identify priority areas for intervention and future research. METHODS: Seven medical, allied health and social science databases were searched from inception to September 2015 in accordance with PRISMA guidelines to identify original peer reviewed articles describing any findings relating to alcohol and/or illicit drug use among refugees, internally displaced people (IDPs), asylum seekers, people displaced by disasters and deportees. A descriptive synthesis of evidence from quantitative studies was conducted, focusing primarily on studies which used validated measures of substance use. Synthesis of evidence from qualitative studies focused on identifying prominent themes relating to the contexts and consequences of substance use. Critical Appraisal Skills Programme (CASP) checklists were used to assess methodological quality of included studies. RESULTS: Forty-four quantitative (82% cross-sectional), 16 qualitative and three mixed-methods studies were included. Ten studies were rated as high methodological quality (16%), 39 as moderate quality (62%) and 14 as low quality (22%). The majority of research was conducted among refugees, IDPs and asylum seekers (n = 55, 87%), predominantly in high-income settings. The highest-quality prevalence estimates of hazardous/harmful alcohol use ranged from 17%-36% in camp settings and 4%-7% in community settings. Few studies collected validated measures of illicit drug use. Seven studies compared substance use among forced migrants to other migrant or native-born samples. Among eight studies which conducted multivariable analysis, male sex, trauma exposure and symptoms of mental illness were commonly identified correlates of substance use. CONCLUSION: Our understanding of substance use among forced migrants remains limited, particularly regarding persons displaced due to disasters, development and deportation. Despite a growing body of work among refugee-background populations, few studies include refugees in low and middle-income countries, where over 80% of the global refugee population resides. Findings suggest a need to integrate substance use prevention and treatment into services offered to forced migrants, particularly in camp settings. Efforts to develop and evaluate interventions to reduce substance use and related harms are needed. PMID- 27411088 TI - Nylon 6,6 Nonwoven Fabric Separates Oil Contaminates from Oil-in-Water Emulsions. AB - Industrial oil spills into aquatic environments can have catastrophic environmental effects. First responders to oil spills along the coast of the Gulf of Mexico in the southern United States have used spunbond nylon fabric bags and fences to separate spilled oil and oil waste from contaminated water. Low area mass density spunbond nylon is capable of sorbing more than 16 times its mass in low viscosity crude oil and more than 26 times its mass in higher viscosity gear lube oil. Nylon bags separated more than 95% of gear lube oil contaminate from a 4.5% oil-in-water emulsion. Field testing of spunbond nylon fences by oil spill first responders has demonstrated the ability of this material to contain the oily contaminate while allowing water to flow through. We hypothesize that the effectiveness of nylon as an oil filter is due to the fact that it is both more oleophilic and more hydrophilic than other commonly used oil separation materials. The nylon traps oil droplets within the fabric or on the surface, while water droplets are free to flow through the fabric to the water on the opposite side of the fabric. PMID- 27411089 TI - Thermally Stable Super Ionic Conductor from Carbon Sphere Oxide. AB - A highly stable proton conductor has been developed from carbon sphere oxide (CSO). Carbon sphere (CS) generated from sucrose was oxidized successfully to CSO using Hummers' graphite oxidation technique. At room temperature and 90 % relative humidity, the proton conductivity of thin layer CSO on microsized comb electrode was found to be 8.7*10(-3) S cm(-1) , which is higher than that for a similar graphene oxide (GO) sample (3.4*10(-3) S cm(-1) ). The activation energy (Ea ) of 0.258 eV suggests that the proton is conducted through the Grotthuss mechanism. The carboxyl functional groups on the CSO surface are primarily responsible for transporting protons. In contrast to conventional carbon-based proton conductors, in which the functional groups decompose around 80 degrees C, CSO has a stable morphology and functional groups with reproducible proton conductivity up to 400 degrees C. Even once annealed at different temperatures at high relative humidity, the proton conductivity of CSO remains almost unchanged, whereas significant change is seen with a similar GO sample. After annealing at 100 and 200 degrees C, the respective proton conductivity of CSO was almost the same, and was about ~50 % of the proton conductivity at room temperature. Carbon-based solid electrolyte with such high thermal stability and reproducible proton conductivity is desired for practical applications. We expect that a CSO-based proton conductor would be applicable for fuel cells and sensing devices operating under high temperatures. PMID- 27411090 TI - Landscape-scale variation in an anthropogenic factor shapes immune gene variation within a wild population. AB - Understanding the spatial scale at which selection acts upon adaptive genetic variation in natural populations is fundamental to our understanding of evolutionary ecology, and has important ramifications for conservation. The environmental factors to which individuals of a population are exposed can vary at fine spatial scales, potentially generating localized patterns of adaptation. Here, we compared patterns of neutral and major histocompatibility complex (MHC) variation within an island population of Berthelot's pipit (Anthus berthelotii) to assess whether landscape-level differences in pathogen-mediated selection generate fine-scale spatial structuring in these immune genes. Specifically, we tested for spatial associations between the distribution of avian malaria, and the factors previously shown to influence that distribution, and MHC variation within resident individuals. Although we found no overall genetic structure across the population for either neutral or MHC loci, we did find localized associations between environmental factors and MHC variation. One MHC class I allele (ANBE48) was directly associated with malaria infection risk, while the presence of the ANBE48 and ANBE38 alleles within individuals correlated (positively and negatively, respectively) with distance to the nearest poultry farm, an anthropogenic factor previously shown to be an important determinant of disease distribution in the study population. Our findings highlight the importance of considering small spatial scales when studying the patterns and processes involved in evolution at adaptive loci. PMID- 27411091 TI - Correction: Patterns and Trends in Accidental Poisoning Deaths: Pennsylvania's Experience 1979-2014. AB - [This corrects the article DOI: 10.1371/journal.pone.0151655.]. PMID- 27411092 TI - A Robust Analytical Pipeline for Genome-Wide Identification of the Genes Regulated by a Transcription Factor: Combinatorial Analysis Performed Using gSELEX-Seq and RNA-Seq. AB - For identifying the genes that are regulated by a transcription factor (TF), we have established an analytical pipeline that combines genomic systematic evolution of ligands by exponential enrichment (gSELEX)-Seq and RNA-Seq. Here, SELEX was used to select DNA fragments from an Aspergillus nidulans genomic library that bound specifically to AmyR, a TF from A. nidulans. High-throughput sequencing data were obtained for the DNAs enriched through the selection, following which various in silico analyses were performed. Mapping reads to the genome revealed the binding motifs including the canonical AmyR-binding motif, CGGN8CGG, as well as the candidate promoters controlled by AmyR. In parallel, differentially expressed genes related to AmyR were identified by using RNA-Seq analysis with samples from A. nidulans WT and amyR deletant. By obtaining the intersecting set of genes detected using both gSELEX-Seq and RNA-Seq, the genes directly regulated by AmyR in A. nidulans can be identified with high reliability. This analytical pipeline is a robust platform for comprehensive genome-wide identification of the genes that are regulated by a target TF. PMID- 27411093 TI - Dangerous hitchhikers? Evidence for potentially pathogenic Vibrio spp. on microplastic particles. AB - The taxonomic composition of biofilms on marine microplastics is widely unknown. Recent sequencing results indicate that potentially pathogenic Vibrio spp. might be present on floating microplastics. Hence, these particles might function as vectors for the dispersal of pathogens. Microplastics and water samples collected in the North and Baltic Sea were subjected to selective enrichment for pathogenic Vibrio species. Bacterial colonies were isolated from CHROMagarTMVibrio and assigned to Vibrio spp. on the species level by MALDI-TOF MS (Matrix Assisted Laser Desorption/Ionisation - Time of Flight Mass Spectrometry). Respective polymers were identified by ATR FT-IR (Attenuated Total Reflectance Fourier Transform - Infrared Spectroscopy). We discovered potentially pathogenic Vibrio parahaemolyticus on a number of microplastic particles, e.g. polyethylene, polypropylene and polystyrene from North/Baltic Sea. This study confirms the indicated occurrence of potentially pathogenic bacteria on marine microplastics and highlights the urgent need for detailed biogeographical analyses of marine microplastics. PMID- 27411094 TI - Association between Clinical and Doppler Echocardiographic Parameters with Sudden Death in Hemodialysis Patients. AB - BACKGROUND: Sudden cardiac death (SCD) is the leading cause of death in maintenance hemodialysis (HD) patients, but there is little information about underlying risk factors. OBJECTIVES: Evaluate the association between clinical and echocardiographic variables with SCD on HD patients. METHODS: Retrospective nested case-control study on chronic HD patients who were prospectively followed. The primary endpoint was SCD. Variables were compared by Student t test, Mann Whitney or Chi-Square, and independent predictors of SCD were evidenced by multivariate logistic regression. RESULTS: We followed 153 patients (50 +/- 15 years, 58% men) for 23 +/- 14 months and observed 35 deaths, 17 of which were SCD events. When compared to the control group (matched for gender, age, and body mass index) there were no differences regarding time on dialysis, traditional biochemical parameters, blood pressure, smoking, use of cardiovascular protective drugs, ejection fraction, left ventricular dimensions, and diastolic function indices. On the other hand, in the SCD group, we found a higher prevalence of previous heart failure, acute myocardial infarction and diabetes, greater left ventricular mass index, greater left atrial size and lower global myocardial performance. After multivariate logistic regression analysis, diabetes (OR = 2.6; CI = 1.3-7.5; p = 0.023) and left ventricular mass index >= 101 g/m2.7 (OR = 1.04; CI = 1.01-1.08; p = 0.028) showed independent association with SCD events. CONCLUSIONS: HD patients with diabetes mellitus and left ventricular hypertrophy appear to have the highest risk of SCD. Preventive and therapeutic strategies should be encouraged in addressing these risk factors to minimize the occurrence of SCD in HD patients. PMID- 27411095 TI - Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats. AB - BACKGROUND: Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH) in rats has not been elucidated thus far. OBJECTIVE: The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of alpha-myosin heavy chain (MHC) and beta-MHC isoforms. METHODS: Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of alpha- MHC and beta-MHC were measured by qPCR. RESULTS: Baseline LVDP (74.0 +/- 3.1 vs. 92.5 +/- 3.2 mmHg, p < 0.05) and heart rate (217 +/- 11 vs. 273 +/- 6 beat/min, p < 0.05) were lower in the FH rats than controls. Also, these results showed the same significance in +/-dp/dt. In the FH rats, beta-MHC expression was higher (201%) and alpha- MHC expression was lower (47%) than control. CONCLUSION: Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of beta-MHC to alpha- MHC ratio in the heart. PMID- 27411096 TI - Is Local Nitric Oxide Availability Responsible for Myocardial Salvage after Remote Preconditioning? AB - BACKGROUND: Remote ischemic preconditioning (RIPC) represents an attractive therapy for myocardial protection, particularly when ischemic events can be anticipated. Although several hypothetic mechanisms have been proposed, no definite molecular pathways have been elucidated. OBJECTIVE: We evaluated the effect of brachial circulation cuff occlusion on myocardial ischemic tolerance, necrosis, and nitric oxide (NO) in patients with ischemic heart disease undergoing elective percutaneous coronary interventions (PCI). METHODS: 46 patients were randomly allocated into two groups: control and RIPC before PCI procedures. Electrocardiographic analysis, serum concentrations of troponin I (cTn-I) were measured at baseline and 24 hours after PCI. A blood sample from the atherosclerotic plaque was drawn to determine nitrate and nitrites. RESULTS: RIPC increased the availability of NO in the stented coronary artery. Control patients presented a small but significant increase in cTn-I, whilst it remained unchanged in preconditioned group. The preconditioning maneuver not only preserved but also enhanced the sum of R waves. CONCLUSIONS: RIPC induced an intracoronary increase of NO levels associated with a decrease in myocardial damage (measured as no increase in cTn-I) with electrocardiographic increases in the sum of R waves, suggesting an improved myocardium after elective PCI. PMID- 27411097 TI - Clinical Course After Cardioverter-Defibrillator Implantation: Chagasic Versus Ischemic Patients. AB - BACKGROUND: The outcome of Chagas disease patients after receiving implantable cardioverter defibrillator (ICD) is still controversial. OBJECTIVE: To compare clinical outcomes after ICD implantation in patients with chronic Chagas cardiomyopathy (CCC) and ischemic heart disease (IHD). METHODS: Prospective study of a population of 153 patients receiving ICD (65 with CCC and 88 with IHD). The devices were implanted between 2003 and 2011. Survival rates and event-free survival were compared. RESULTS: The groups were similar regarding sex, functional class and ejection fraction. Ischemic patients were, on average, 10 years older than CCC patients (p < 0.05). Patients with CCC had lower schooling and monthly income than IHD patients (p < 0.05). The number of appropriate therapies was 2.07 higher in CCC patients, who had a greater incidence of appropriate shock (p < 0.05). Annual mortality rate and electrical storm incidence were similar in both groups. There was no sudden death in CCC patients, and only one in IHD patients. Neither survival time (p = 0.720) nor event-free survival (p = 0.143) significantly differed between the groups. CONCLUSION: CCC doubles the risk of receiving appropriate therapies as compared to IHD, showing the greater complexity of arrhythmias in Chagas patients. PMID- 27411098 TI - Individual and Population Level Resource Selection Patterns of Mountain Lions Preying on Mule Deer along an Urban-Wildland Gradient. AB - Understanding population and individual-level behavioral responses of large carnivores to human disturbance is important for conserving top predators in fragmented landscapes. However, previous research has not investigated resource selection at predation sites of mountain lions in highly urbanized areas. We quantified selection of natural and anthropogenic landscape features by mountain lions at sites where they consumed their primary prey, mule deer (Odocoileus hemionus), in and adjacent to urban, suburban, and rural areas in greater Los Angeles. We documented intersexual and individual-level variation in the environmental conditions present at mule deer feeding sites relative to their availability across home ranges. Males selected riparian woodlands and areas closer to water more than females, whereas females selected developed areas marginally more than males. Females fed on mule deer closer to developed areas and farther from riparian woodlands than expected based on the availability of these features across their home ranges. We suggest that mortality risk for females and their offspring associated with encounters with males may have influenced the different resource selection patterns between sexes. Males appeared to select mule deer feeding sites mainly in response to natural landscape features, while females may have made kills closer to developed areas in part because these are alternative sites where deer are abundant. Individual mountain lions of both sexes selected developed areas more strongly within home ranges where development occurred less frequently. Thus, areas near development may represent a trade-off for mountain lions such that they may benefit from foraging near development because of abundant prey, but as the landscape becomes highly urbanized these benefits may be outweighed by human disturbance. PMID- 27411099 TI - Neonatal McCune-Albright syndrome with survival beyond two years. AB - McCune-Albright syndrome (MAS) is a rare disease resulting from a somatic, mosaic mutation of GNAS1 encoding the Gs alpha subunit of the G-protein coupled membrane receptor responsible for multiple hormonal signaling cascades. We present a patient with neonatal MAS who initially presented with neonatal diabetes and concern for congenital cardiac disease, and subsequently was found to have significant ACTH-independent neonatal Cushing syndrome. Her course included multi system organ involvement, although she initially did not have obvious findings consistent with the MAS classic triad of cafe-au-lait macules, fibrous dysplasia, or peripheral precocious puberty. After medical and surgical treatment, she remains the only reported survivor of neonatal MAS. This clinical report alerts clinicians to the possibility of this disease in neonates with non-classical endocrine and non-endocrine manifestations of MAS, and demonstrates that this very early presentation is potentially survivable. (c) 2016 Wiley Periodicals, Inc. PMID- 27411100 TI - Does Reactance against Cigarette Warning Labels Matter? Warning Label Responses and Downstream Smoking Cessation amongst Adult Smokers in Australia, Canada, Mexico and the United States. AB - OBJECTIVE: Some researchers have raised concerns that pictorial health warning labels (HWLs) on cigarette packages may lead to message rejection and reduced effectiveness of HWL messages. This study aimed to determine how state reactance (i.e., negative affect due to perceived manipulation) in response to both pictorial and text-only HWLs is associated with other types of HWL responses and with subsequent cessation attempts. METHODS: Survey data were collected every 4 months between September 2013 and 2014 from online panels of adult smokers in Australia, Canada, Mexico, and the US were analyzed. Participants with at least one wave of follow-up were included in the analysis (n = 4,072 smokers; 7,459 observations). Surveys assessed psychological and behavioral responses to HWLs (i.e., attention to HWLs, cognitive elaboration of risks due to HWLs, avoiding HWLs, and forgoing cigarettes because of HWLs) and cessation attempts. Participants then viewed specific HWLs from their countries and were queried about affective state reactance. Logistic and linear Generalized Estimating Equation (GEE) models regressed each of the psychological and behavioral HWL responses on reactance, while controlling for socio-demographic and smoking related variables. Logistic GEE models also regressed having attempted to quit by the subsequent survey on reactance, each of the psychological and behavioral HWL responses (analyzed separately), adjustment variables. Data from all countries were initially pooled, with interactions between country and reactance assessed; when interactions were statistically significant, country-stratified models were estimated. RESULTS: Interactions between country and reactance were found in all models that regressed psychological and behavioral HWL responses on study variables. In the US, stronger reactance was associated with more frequent reading of HWLs and thinking about health risks. Smokers from all four countries with stronger reactance reported greater likelihood of avoiding warnings and forgoing cigarettes due to warnings, although the association appeared stronger in the US. Both stronger HWLs responses and reactance were positively associated with subsequent cessation attempts, with no significant interaction between country and reactance. CONCLUSIONS: Reactance towards HWLs does not appear to interfere with quitting, which is consistent with its being an indicator of concern, not a systematic effort to avoid HWL message engagement. PMID- 27411101 TI - Etiologies, Risk Factors and Impact of Severe Diarrhea in the Under-Fives in Moramanga and Antananarivo, Madagascar. AB - BACKGROUND: Diarrheal disease remains a leading cause of death in children in low income countries. We investigated the etiology, risk factors and effects on nutritional status of severe diarrhea in children from two districts in Madagascar. METHODS: We performed a matched case-control study in 2011 to 2014, on children under the age of five years from Moramanga and Antananarivo. The cases were children hospitalized for severe diarrhea and the controls were children without diarrhea selected at random from the community. Stool samples were collected from both groups. Anthropometric measurements were made during follow-up visits about one and two months after enrolment. RESULTS: We enrolled 199 cases and 199 controls. Rotavirus infection was the most frequently detected cause of diarrhea. It was strongly associated with severe diarrhea (OR: 58.3; 95% CI: 7.7-439.9), accounting for 42.4% (95% CI: 37.6-43.1) of severe diarrhea cases. At the household level, possession of cattle (OR = 0.3; 95% CI: 0.1-0.6) and living in a house with electricity (OR = 0.4; 95% CI: 0.2-0.8) were protective factors. The presence of garbage around the house was a risk factor for severe diarrhea (OR = 3.2; 95% CI: 1.9-5.4). We found no significant association between severe diarrhea and the nutritional status of the children at follow-up visits, but evident wasting at enrolment was associated with a higher risk of severe diarrhea (OR = 9; 95% CI: 4.5-17.9). CONCLUSIONS: Severe childhood diarrhea is mostly caused by rotavirus infection. An anti-rotavirus vaccine has already been introduced in Madagascar and should be promoted more widely. However, post-licensing surveillance is required. Interventions to improve the nutritional status of children, preventive measures focused on household and personal hygiene and nutritional rehabilitation during severe diarrheal disease should be reinforced. PMID- 27411102 TI - Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells. AB - There is an urgent need for an efficient approach to obtain a large-scale and renewable source of functional human vascular smooth muscle cells (VSMCs) to establish robust, patient-specific tissue model systems for studying the pathogenesis of vascular disease, and for developing novel therapeutic interventions. Here, we have derived a large quantity of highly enriched functional VSMCs from human induced pluripotent stem cells (hiPSC-VSMCs). Furthermore, we have engineered 3D tissue rings from hiPSC-VSMCs using a facile one-step cellular self-assembly approach. The tissue rings are mechanically robust and can be used for vascular tissue engineering and disease modeling of supravalvular aortic stenosis syndrome. Our method may serve as a model system, extendable to study other vascular proliferative diseases for drug screening. Thus, this report describes an exciting platform technology with broad utility for manufacturing cell-based tissues and materials for various biomedical applications. PMID- 27411103 TI - Glucose-Induced Oxidative Stress Reduces Proliferation in Embryonic Stem Cells via FOXO3A/beta-Catenin-Dependent Transcription of p21(cip1). AB - Embryonic stem cells (ESCs), which are derived from a peri-implantation embryo, are routinely cultured in medium containing diabetic glucose (Glc) concentrations. While pregnancy in women with pre-existing diabetes may result in small embryos, whether such high Glc levels affect ESC growth remains uncovered. We show here that long-term exposure of ESCs to diabetic Glc inhibits their proliferation, thereby mimicking in vivo findings. Molecularly, Glc exposure increased oxidative stress and activated Forkhead box O3a (FOXO3a), promoting increased expression and activity of the ROS-removal enzymes superoxide dismutase and catalase and the cell-cycle inhibitors p21(cip1) and p27(kip1). Diabetic Glc also promoted beta-catenin nuclear localization and the formation of a complex with FOXO3a that localized to the promoters of Sod2, p21(cip1), and potentially p27(kip1). Our results demonstrate an adaptive response to increases in oxidative stress induced by diabetic Glc conditions that promote ROS removal, but also result in a decrease in proliferation. PMID- 27411104 TI - CDK7 and miR-210 Co-regulate Cell-Cycle Progression of Neural Progenitors in the Developing Neocortex. AB - The molecular mechanisms regulating neural progenitor (NP) proliferation are fundamental in establishing the cytoarchitecture of the mammalian neocortex. The rate of cell-cycle progression and a fine-tuned balance between cell-cycle re entry and exit determine the numbers of both NPs and neurons as well as postmitotic neuronal laminar distribution in the cortical wall. Here, we demonstrate that the microRNA (miRNA) miR-210 is required for normal mouse NP cell-cycle progression. Overexpression of miR-210 promotes premature cell-cycle exit and terminal differentiation in NPs, resulting in an increase in early-born postmitotic neurons. Conversely, miR-210 knockdown promotes an increase in the radial glial cell population and delayed differentiation, resulting in an increase in late-born postmitotic neurons. Moreover, the cyclin-dependent kinase CDK7 is regulated by miR-210 and is necessary for normal NP cell-cycle progression. Our findings demonstrate that miRNAs are essential for normal NP proliferation and cell-cycle progress during neocortical development. PMID- 27411105 TI - Immobilized WNT Proteins Act as a Stem Cell Niche for Tissue Engineering. AB - The timing, location, and level of WNT signaling are highly regulated during embryonic development and for the maintenance of adult tissues. Consequently the ability to provide a defined and directed source of WNT proteins is crucial to fully understand its role in tissue development and to mimic its activity in vitro. Here we describe a one-step immobilization technique to covalently bind WNT3A proteins as a basal surface with easy storage and long-lasting activity. We show that this platform is able to maintain adult and embryonic stem cells while also being adaptable for 3D systems. Therefore, this platform could be used for recapitulating specific stem cell niches with the goal of improving tissue engineering. PMID- 27411106 TI - Antenatal steroid exposure in the late preterm period is associated with reduced cord blood neurotrophin-3. AB - BACKGROUND: Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (<32weeks gestation) who subsequently develop brain injury. Antenatal steroid exposure can alter neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population. AIM: To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure. STUDY DESIGN: Retrospective analysis. SUBJECTS: Late preterm infants (33-36weeks; n=119) and term infants (37-41weeks; n=129) born at the Women's and Children's Hospital, Adelaide. OUTCOME MEASURES: Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA. RESULTS: Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p<0.001), while BDNF and NT-3 were not different. In the late preterm period, cord blood NT-3 was reduced when antenatal steroids were administered >24h prior to delivery (p<0.01). CONCLUSION: This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period. PMID- 27411107 TI - Early general movements and brain magnetic resonance imaging at term-equivalent age in infants born <30weeks' gestation. AB - BACKGROUND: Neurodevelopmental assessments and brain magnetic resonance imaging (MRI) at term-equivalent age (TEA) predict developmental outcomes in preterm infants. However, the relationship between neurodevelopment prior to term and cerebral structure is currently unknown. AIMS: To examine the relationships between General Movements (GMs) assessed from birth to TEA and brain MRI at TEA in infants born <30weeks' gestation. STUDY DESIGN: Prospective cohort study. GMs (categorised as 'normal' or 'abnormal') were recorded weekly from birth to 32weeks, and at 34 and 36weeks' postmenstrual age. At TEA, GMs were assessed concurrently with brain MRI (using a validated scoring system). SUBJECTS: 149 infants born <30weeks' gestation were recruited from a tertiary hospital. RESULTS: 103 infants had MRI at TEA and GMs recorded. Abnormal GMs prior to term were associated with cortical grey matter abnormality (p<0.03), deep grey matter abnormality (p=0.02) and increased interhemispheric distance (p<0.02). Abnormal GMs at TEA (n=55/90) were associated with more global brain abnormality (p<0.01) and cortical grey matter abnormality (p=0.01), and decreased transcerebellar diameter (p=0.04) on concurrent brain MRI. CONCLUSIONS: Abnormal GMs both prior to term and at TEA were associated with more marked brain abnormality, and smaller brains at TEA. Abnormal GMs are an early marker of brain abnormalities in very preterm infants. PMID- 27411108 TI - The Classification of Anxiety and Fear-Related Disorders in the ICD-11. AB - Anxiety disorders are highly prevalent worldwide and engender substantial economic costs and disability. The World Health Organization is currently developing the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11), which represents the first opportunity to improve the validity, clinical utility, and global applicability of the classification in more than 25 years. This article describes changes in the organization and diagnostic guidelines for anxiety and fear-related disorders proposed by the ICD-11 Working Group on the Classification of Mood and Anxiety Disorders and the rationale and evidence base for the proposals. In ICD-11, anxiety and fear-related disorders that manifest across the lifespan are brought together under a new grouping, and are partly distinguished by their focus of apprehension. The focus of apprehension is the stimulus or situation that triggers the fear or anxiety and may be highly specific as in specific phobia or relate to a broader class of situations as in social anxiety disorder. The guidelines also clarify the relationship between panic disorder and agoraphobia and a qualifier is provided for panic attacks in the context of other disorders. A standardized format emphasizing essential features of anxiety disorders is intended to improve clinical utility. Guidelines will be further refined based on findings from two types of field studies: those using a case-controlled vignette methodology disseminated via the Internet to practitioners worldwide (http://gcp.network) and clinic-based field trials implemented globally at participating field study centers. PMID- 27411109 TI - School-age children enjoyed good respiratory health and fewer allergies despite having lung disease after preterm birth. AB - AIM: This study explored the under-researched area of whether preterm birth or bronchopulmonary dysplasia (BPD) affected hospitalisation rates, allergies or health-related quality of life (HRQoL). METHODS: We studied 88 schoolchildren born preterm at a mean gestational age of 28.8 weeks (range 24.1-31.9) and matched term-born controls at the mean age of 11 years (range 8-14). Hospitalisations after the first discharge were recorded, skin prick allergy tests were performed and HRQoL was assessed with a parental questionnaire. RESULTS: Preterm children were hospitalised more than controls (64% versus 39%, p = 0.001), mostly before two years of age. The adjusted odds ratios (OR) for two year-old preterm-born children being hospitalised for wheezing was 8.2 (95% CI 2.0-34.1). BPD affected 56% of the preterm children, but did not influence hospitalisations, and the positive skin prick rate was similar between the preterm and term-born children (35% versus 48%, p = 0.126). Preterm BPD children had fewer positive skin prick tests than those without BPD. HRQoL was lower in preterm than term children (81.25 +/- 10.84 versus 86.80 +/- 9.60, p = 0.001). CONCLUSION: Most health problems experienced by preterm-born schoolchildren occurred before two years of age and were mainly wheezing disorders. BPD decreased atopy but had no influence on hospitalisation rates. PMID- 27411110 TI - Errata: From Jobsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase. PMID- 27411111 TI - Fast and scalable algorithm for the simulation of multiple Mie scattering in optical systems. AB - The Monte Carlo simulation of light propagation in optical systems requires the processing of a large number of photons to achieve a satisfactory statistical accuracy. Based on classical Mie scattering, we experimentally show that the independence of photons propagating through a turbid medium imposes a postulate for a concurrent and scalable programming paradigm of general purpose graphics processing units. This ensures that, without rewriting code, increasingly complex optical systems can be simulated if more processors are available in the future. PMID- 27411112 TI - Spatial light coupled into a single-mode fiber by a Maksutov-Cassegrain antenna through atmospheric turbulence. AB - Maksutov-Cassegrains are widely used in free-space optical communication. The coupling efficiency and variance of a Maksutov-Cassegrain fiber (single-mode) system distorted by atmospheric turbulence are numerically evaluated using second order and fourth-order moments under a Von Karman spectrum. Considering the limited cost and size of the equipment, the Maksutov-Cassegrain aperture should satisfy DA/rhoS~7 (rhoS approximates the characteristic atmospheric coherence length), and the obscuration ratio should be no more than 0.2. PMID- 27411113 TI - Visibility measurements using two-angle forward scattering by liquid droplets. AB - This study presents a two-angle forward scattering (TAFS) method that can be used to detect atmosphere visibility and distinguish different weather phenomena. The visibility measuring instrument has two receivers arranged at the forward scattering angles of 35 degrees and 90 degrees , and the atmosphere visibility is measured by the first receiver (35 degrees ). We use the ratio between the scattering phase functions P(35 degrees ) and P(90 degrees ) to judge the asymmetry parameter of atmospheric particles and to distinguish the weather phenomenon. Compared with multi-angle forward scattering (MAFS) that can distinguish fog, haze, and mist, TAFS can determine additional weather phenomena (i.e., normal weather and rain) and has fewer receivers. Thus, we improve the instrument design of this method whose visibility error is smaller than that of MAFS on rainy days. PMID- 27411114 TI - Analytical calculation of the light-collection efficiency of an optical emission spectrometer with the effective solid-angle method. AB - A method is proposed for calculating the optical emission spectrometer (OES) light-collection efficiency using the effective solid angle from an arbitrary point source. Based on the point source-OES relative positioning, the effective solid angle is derived for four cases: (1) on axis and on the object plane; (2) on axis and outside the object plane; (3) off axis and on the object plane; and (4) off axis and outside the object plane. The results were in good agreement with those obtained through Monte Carlo ray tracing. After calculating the OES geometrical collection efficiency with respect to the object plane distance in three different-sized cylindrical volume sources, we suggest a simple strategy to increase this efficiency in plasma process monitoring. PMID- 27411115 TI - Doppler shift generated by a moving diffraction grating under incidence by polychromatic diffuse light. AB - We consider the spectral response of moving diffraction gratings, in which the incident light extends over a broad angular range and where the diffracted light is observed from a specific angle. We show that the dispersion relation between the frequency perceived by an observer who is looking at a moving grating and the incident frequency can exhibit some unique features, such as a flat band (i.e., a local minimum). An observer can see the light diffracted into a nonspecular diffraction order from a multitude of incident light rays, and the angle of incidence of each ray is frequency dependent; as a consequence, when the grating is moving, each incident ray experiences a Doppler shift in frequency that depends on its angle of incidence. We find that remarkable features appear near a Wood anomaly where the angle of incidence, for a given diffraction angle, can change very quickly with frequency. This means that light of multiple frequencies and incident from multiple angles can be mixed by the motion of the grating into the same diffracted ray and their frequencies can be compressed into a narrower range. The existence of a flat band means that a moving grating can be used as a device to increase the intensity of the perceived diffracted light due to spectral compression. The properties of a grating in motion in sunlight can also be relevant to the study of naturally occurring gratings which are typically in oscillatory motion. PMID- 27411116 TI - Simplified optical correlation-domain reflectometry without reference path. AB - We develop a simplified configuration for optical correlation-domain reflectometry (OCDR) without an explicit reference path. Instead, the Fresnel reflected light generated at the distal open end of the sensing fiber is exploited as a reference light. After the fundamental demonstration, the optimal incident power is found to be approximately 8 dBm. We also show that the loss near the distal end should not be applied, unlike in the case of Brillouin-based OCDR. PMID- 27411117 TI - Super-resolution imaging of photonic crystals using the dual-space microscopy technique. AB - We present an experimental implementation of the recently proposed dual-space microscopy (DSM), an optical microscopy technique based on simultaneous observation of an object in the position and momentum spaces, using computer controlled hemispherical digital condensers. We demonstrate that DSM is capable of resolving structures below the Rayleigh resolution limit. PMID- 27411118 TI - Accurate alignment of optical axes of a biplate using a spectroscopic Mueller matrix ellipsometer. AB - The biplate that consists of two single wave plates made from birefringent materials with their fast axes oriented perpendicular to each other is one of the most commonly used retarders in many optical systems. The internal alignment of the optical axes of the two single wave plates is a key procedure in the fabrication and application of a biplate to reduce the spurious artifacts of oscillations in polarization properties due to the misalignment error and to improve the accuracy and precision of the systems using such biplates. In this paper, we propose a method to accurately align the axes of an arbitrary biplate by minimizing the oscillations in the characteristic parameter spectra of the biplate detected by a spectroscopic Mueller matrix ellipsometer (MME). We derived analytical relations between the characteristic parameters and the misalignment error in the biplate, which helps us to analyze the sensitivity of the characteristic parameters to the misalignment error and to evaluate the alignment accuracy quantitatively. Experimental results performed on a house-developed MME demonstrate that the alignment accuracy of the proposed method is better than 0.01 degrees in aligning the optical axes of a quartz biplate. PMID- 27411119 TI - Analytical approximation for photonic array modes in two-dimensional photonic crystal lattices. AB - We presented here a comprehensive analytical approximation, describing array modes (both the modal fields and their associated propagation constants) in 2D photonic lattices (i.e., arrays of identical coupled waveguides/lasers). Our approximation is a vectorial approach, accounting for the TE and TM polarizations. It is applicable to both the low-contrast and high-contrast photonic devices. The model of standing waves of a membrane was used for analytical evaluation of envelopes of the array modes and the total modal fields. Combination of this model with the coupled-mode formalism for 2D infinite photonic lattices allowed for evaluation of propagation constants of the array modes. Both the computations required only a few seconds. Still, the results, acquired with the analytical approximation, are in close agreement with those acquired with well-established approaches. Moreover, for the first time, analytical expressions for the modal fields and propagation constants become available. PMID- 27411120 TI - High-security communication by coherence modulation at the photon-counting level. AB - We show that key-specified interferometer path-length difference modulation (often referred to as coherence modulation), operating in the photon-counting regime with a broadband source, can provide a quantifiably high level of physics guaranteed security for binary signal transmission. Each signal bit is associated with many photocounts, perhaps numbering in the thousands. Of great importance, the presence of an eavesdropper can be quickly detected. We first review the operation of key-specified coherence modulation at high light levels, illustrating by means of an example its lack of security against attack. We then show, using the same example, that, through the reduction of light intensities to photon-counting levels, a high level of security can be attained. A particular attack on the system is analyzed to demonstrate the quantifiability of the scheme's security, and various remaining research issues are discussed. A potential weakness of the scheme lies in a possible vulnerability to light amplification by an attacker. PMID- 27411121 TI - Three-element trap filter radiometer based on large active area silicon photodiodes. AB - This paper shows the opto-mechanical design of a new filter radiometer built at the Physikalisch-Technische Bundesanstalt, Germany, for the accurate determination of the thermodynamic temperature of high-temperature blackbodies. The filter radiometer is based on a three-element reflection-type trap detector that uses three large active area silicon photodiodes. Its spectral coverage and field of view are defined by a detachable narrow-band filter and a diamond-turned precision aperture, respectively. The temperature of the filter radiometer is stabilized using a water-streamed housing and is measured using a thin-film platinum thermometer placed onto the first photodiode element. The trap "mount" has been made as compact as possible, which, together with the large active area of the chosen photodiodes, allows a wide field of view. This work presents the design of the filter radiometer and discusses the criteria that have been considered in order for the filter radiometer to suit the application. PMID- 27411122 TI - Stray light effects in above-water remote-sensing reflectance from hyperspectral radiometers. AB - Stray light perturbations are unwanted distortions of the measured spectrum due to the nonideal performance of optical radiometers. Because of this, stray light characterization and correction is essential when accurate radiometric measurements are a necessity. In agreement with such a need, this study focused on stray light correction of hyperspectral radiometers widely applied for above water measurements to determine the remote-sensing reflectance (RRS). Stray light of sample radiometers was experimentally characterized and a correction algorithm was developed and applied to field measurements performed in the Mediterranean Sea. Results indicate that mean stray light corrections are appreciable, with values generally varying from -1% to +1% in the 400-700 nm spectral region for downward irradiance and sky radiance, and from -1% to +4% for total radiance from the sea. Mean corrections for data products such as RRS exhibit values that depend on water type varying between -0.5% and +1% in the blue-green spectral region, with peaks up to 9% in the red in eutrophic waters. The possibility of using one common stray light correction matrix for the analyzed class of radiometers was also investigated. Results centered on RRS support such a feasibility at the expense of an increment of the uncertainty typically well below 0.5% in the blue-green and up to 1% in the red, assuming sensors are based on spectrographs from the same production batch. PMID- 27411123 TI - Spectral-overlap approach to multiframe superresolution image reconstruction. AB - Various techniques and algorithms have been developed to improve the resolution of sensor-aliased imagery captured with multiple subpixel-displaced frames on an undersampled pixelated image plane. These dealiasing algorithms are typically known as multiframe superresolution (SR), or geometric SR to emphasize the role of the focal-plane array. Multiple low-resolution (LR) aliased frames of the same scene are captured and allocated to a common high-resolution (HR) reconstruction grid, leading to the possibility of an alias-free reconstruction, as long as the HR sampling rate is above the Nyquist rate. Allocating LR-frame irradiances to HR frames requires the use of appropriate weights. Here we present a novel approach in the spectral domain to calculating exactly weights based on spatial overlap areas, which we call the spectral-overlap (SO) method. We emphasize that the SO method is not a spectral approach but rather an approach to calculating spatial weights that uses spectral decompositions to exploit the array properties of the HR and LR pixels. The method is capable of dealing with arbitrary aliasing factors and interframe motions consisting of in-plane translations and rotations. We calculate example reconstructed HR images (the inverse problem) from synthetic aliased images for integer and for fractional aliasing factors. We show the utility of the SO-generated overlap-area weights in both noniterative and iterative reconstructions with known or unknown aliasing factor. We show how the overlap weights can be used to generate the Green's function (pixel response function) for noniterative dealiasing. In addition, we show how the overlap-area weights can be used to generate synthetic aliased images (the forward problem). We compare the SO approach to the spatial-domain geometric approach of O'Rourke and find virtually identical high accuracy but with significant enhancements in speed for SO. We also compare the SO weights to interpolated weights and find that the overlap-area weights lead to significantly smaller errors in iterative reconstructions. We consider how the SO method might be extended to account for the influence of the optical transfer function, more complex or space-variant motions, the registration process, and noise. PMID- 27411124 TI - Coherent frequency-modulated continuous wave reflectometry for measuring stationary Brillouin grating induced under uniform pumping by counterpropagating nonmodulated light waves. AB - We describe theoretically and experimentally how valuable information on the distributed Brillouin spectra of an optical waveguide is derived from the stationary Brillouin grating measurement under uniform pumping over the waveguide by using the coherent frequency-modulated continuous wave reflectometry. We upconvert the frequencies of the probe and pumping light waves by the Brillouin frequency with one modulator and detect the Stokes light in the same way that we detect the Fresnel and Rayleigh backreflections in the fiber. The intrinsic coherent spike is reduced by using the lock-in detection and the least squares method to reveal the distributed Brillouin spectra of a short optical fiber consisting of two different fibers spliced together. PMID- 27411125 TI - Monolithic fiber end cap collimator for high-power free-space fiber-fiber coupling. AB - In this paper, we present the design, construction, and testing of a monolithic fiber end cap collimator for high-power free-space fiber-fiber coupling applications. The collimator is based on a large-sized fiber end cap and a spherical lens design on the output facet. Values of the spot size and working distance are theoretically analyzed based on Gaussian approximation and ABCD transmission matrix. The free-space fiber-fiber coupling process is also analyzed for different lens curvature radii and coupling distances. In the experiment, a collimated laser beam is obtained with Rayleigh length of about 400 mm. A high power laser with 1.1 kW output is tested on the end cap collimator, which only heats up by 7 degrees C at the output facet without active cooling. Free-space fiber-fiber coupling between two 20/400 MUm fibers is achieved based on these collimators, with measured coupling loss lower than 0.3 dB. PMID- 27411126 TI - Optical remote sensor for peanut kernel abortion classification. AB - In this paper, we propose a simple, inexpensive optical device for remote measurement of various agricultural parameters. The sensor is based on temporal tracking of backreflected secondary speckle patterns generated when illuminating a plant with a laser and while applying periodic acoustic-based pressure stimulation. By analyzing different parameters using a support-vector-machine based algorithm, peanut kernel abortion can be detected remotely. This paper presents experimental tests which are the first step toward an implementation of a noncontact device for the detection of agricultural parameters such as kernel abortion. PMID- 27411127 TI - Photorefractive two-beam coupling joint transform correlator: modeling and performance evaluation. AB - The photorefractive two-beam coupling joint transform correlator combines two features. The first is embedded semi-adaptive optimality, which weighs the correlation against clutter and noise in the input, and the second is the intrinsic dynamic range compression nonlinearity, which improves several metrics simultaneously without metric trade-off. Although the two beam coupling correlator was invented many years ago, its outstanding performance was recognized on only relatively simple images. There was no study about the performance of this correlator on complicated images and using different figures of merit. In this paper, the study is extended to more complicated images. For the first time, to our knowledge, we demonstrate simultaneous improvement in metrics performance without metric trade-off. The performance was evaluated compared to the classical joint transform correlator. A typical experimental result to validate the simulation results was also shown in this work. The best performing operation parameters were identified to guide the experimental work and for future comparison with other well-known optimal correlation filters. PMID- 27411128 TI - Speckle-reduction algorithm for ultrasound images in complex wavelet domain using genetic algorithm-based mixture model. AB - Compared with other medical-imaging modalities, ultrasound (US) imaging is a valuable way to examine the body's internal organs, and two-dimensional (2D) imaging is currently the most common technique used in clinical diagnoses. Conventional 2D US imaging systems are highly flexible cost-effective imaging tools that permit operators to observe and record images of a large variety of thin anatomical sections in real time. Recently, 3D US imaging has also been gaining popularity due to its considerable advantages over 2D US imaging. It reduces dependency on the operator and provides better qualitative and quantitative information for an effective diagnosis. Furthermore, it provides a 3D view, which allows the observation of volume information. The major shortcoming of any type of US imaging is the presence of speckle noise. Hence, speckle reduction is vital in providing a better clinical diagnosis. The key objective of any speckle-reduction algorithm is to attain a speckle-free image while preserving the important anatomical features. In this paper we introduce a nonlinear multi-scale complex wavelet-diffusion based algorithm for speckle reduction and sharp-edge preservation of 2D and 3D US images. In the proposed method we use a Rayleigh and Maxwell-mixture model for 2D and 3D US images, respectively, where a genetic algorithm is used in combination with an expectation maximization method to estimate mixture parameters. Experimental results using both 2D and 3D synthetic, physical phantom, and clinical data demonstrate that our proposed algorithm significantly reduces speckle noise while preserving sharp edges without discernible distortions. The proposed approach performs better than the state-of-the-art approaches in both qualitative and quantitative measures. PMID- 27411129 TI - Unequal a priori probability multiple hypothesis testing in space domain awareness with the space surveillance telescope. AB - This paper investigates the ability to improve Space Domain Awareness (SDA) by increasing the number of detectable Resident Space Objects (RSOs) from space surveillance sensors. With matched filter based techniques, the expected impulse response, or Point Spread Function (PSF), is compared against the received data. In the situation where the images are spatially undersampled, the modeled PSF may not match the received data if the RSO does not fall in the center of the pixel. This aliasing can be accounted for with a Multiple Hypothesis Test (MHT). Previously, proposed MHTs have implemented a test with an equal a priori prior probability assumption. This paper investigates using an unequal a priori probability MHT. To determine accurate a priori probabilities, three metrics are computed; they are correlation, physical distance, and empirical. Using the calculated a priori probabilities, a new algorithm is developed, and images from the Space Surveillance Telescope (SST) are analyzed. The number of detected objects by both an equal and unequal prior probabilities are compared while keeping the false alarm rate constant. Any additional number of detected objects will help improve SDA capabilities. PMID- 27411130 TI - Measurement of mean thickness of transparent samples using simultaneous phase shifting interferometry with four interferograms. AB - In this research a novel interferometric system is reported, which allows the generation of four simultaneous interferograms with phase shifts of pi/2. The system consists of three coupled interferometers: a rectangular Sagnac interferometer which generates a primary pattern with crossed circular polarizations, coupled to two Michelson interferometers which operate as a multiplexing system, and generating replicas of the primary pattern. The two coupled Michelson interferometers generate four patterns retaining their polarization properties, which allow independent phase shifts by placing a linear polarizer over each pattern, thereby, four interferograms with relative phase shifts of pi/2 are obtained. The optical phase is calculated using the well-known four-step algorithm. With knowledge of the optical phase, different properties of the samples can be calculated or analyzed; in this case, by knowing the mean refractive index, we can calculate the mean thickness of test objects. The results obtained for static transparent samples are presented. The capability of the system to analyze dynamic events is shown when results for the calculation of a temperature field of a heat flow are presented. PMID- 27411131 TI - Multiple-3D-object secure information system based on phase shifting method and single interference. AB - We propose a multiple-3D-object secure information system for encrypting multiple three-dimensional (3D) objects based on the three-step phase shifting method. During the decryption procedure, five phase functions (PFs) are decreased to three PFs, in comparison with our previous method, which implies that one cross beam splitter is utilized to implement the single decryption interference. Moreover, the advantages of the proposed scheme also include: each 3D object can be decrypted discretionarily without decrypting a series of other objects earlier; the quality of the decrypted slice image of each object is high according to the correlation coefficient values, none of which is lower than 0.95; no iterative algorithm is involved. The feasibility of the proposed scheme is demonstrated by computer simulation results. PMID- 27411132 TI - Sum regression decomposition of spectral and angle-resolved Mueller matrices from biological reflectors. AB - We show spectroscopic Mueller-matrix data measured at multiple incidence angles of the scarab beetle C. aurata. A method of regression decomposition can decompose the Mueller matrix into a set of two matrices representing one polarizer and one dielectric reflector. We also report on a tentative decomposition of the beetle C. argenteola using the same method. PMID- 27411133 TI - Cascaded gain fibers for increasing output power and the stimulated Brillouin scattering threshold of narrow linewidth fiber Raman amplifiers. AB - We show both experimentally and theoretically a method to increase the stimulated Brillouin scattering (SBS) threshold and output power of narrow linewidth fiber Raman amplifiers. This method employs two or more fibers with varying concentrations of the Raman gain material dopant such as GeO2 or P2O5 in silicate-based glasses. These fibers are then cascaded to form an amplifier gain stage, disrupting the buildup of SBS that normally occurs in single continuous fibers. The numerical model shown is applicable to arbitrary amplifier systems for gain stage optimization and increased power scaling. We give experimental results for phosphosilicate fibers that agree well with simulation predictions that support the numerical model used. PMID- 27411134 TI - Parameter correction method for dual position-sensitive-detector-based unit. AB - A dual position-sensitive-detector (PSD)-based unit can be used for angular measurements of a multi-degree-of-freedom measurement system and a laser interferometry-based sensing and tracking system. In order to ensure the precision of incident beam direction measurement for a PSD-based unit, model and autoreflection alignment methods for correction of PSD-based unit parameters are proposed. Experimental results demonstrate the deviations between the angular measurements obtained using a dual PSD-based unit and an autocollimator varied by 70", 20", and 1" for three runs of the autoreflection alignment method, respectively, and the model method deviations all varied by 1" in the 1000" measurement range for three runs. It is therefore concluded that the model method is more reliable than the autoreflection alignment method for ensuring the accuracy of a dual PSD-based unit. PMID- 27411135 TI - Gaussian beam propagation in anisotropic turbulence along horizontal links: theory, simulation, and laboratory implementation. AB - Experimental and theoretical work has shown that atmospheric turbulence can exhibit "non-Kolmogorov" behavior including anisotropy and modifications of the classically accepted spatial power spectral slope, -11/3. In typical horizontal scenarios, atmospheric anisotropy implies that the variations in the refractive index are more spatially correlated in both horizontal directions than in the vertical. In this work, we extend Gaussian beam theory for propagation through Kolmogorov turbulence to the case of anisotropic turbulence along the horizontal direction. We also study the effects of different spatial power spectral slopes on the beam propagation. A description is developed for the average beam intensity profile, and the results for a range of scenarios are demonstrated for the first time with a wave optics simulation and a spatial light modulator-based laboratory benchtop counterpart. The theoretical, simulation, and benchtop intensity profiles show good agreement and illustrate that an elliptically shaped beam profile can develop upon propagation. For stronger turbulent fluctuation regimes and larger anisotropies, the theory predicts a slightly more elliptical form of the beam than is generated by the simulation or benchtop setup. The theory also predicts that without an outer scale limit, the beam width becomes unbounded as the power spectral slope index alpha approaches a maximum value of 4. This behavior is not seen in the simulation or benchtop results because the numerical phase screens used for these studies do not model the unbounded wavefront tilt component implied in the analytic theory. PMID- 27411136 TI - Automated decomposition algorithm for Raman spectra based on a Voigt line profile model. AB - Raman spectra measured by spectrometers usually suffer from band overlap and random noise. In this paper, an automated decomposition algorithm based on a Voigt line profile model for Raman spectra is proposed to solve this problem. To decompose a measured Raman spectrum, a Voigt line profile model is introduced to parameterize the measured spectrum, and a Gaussian function is used as the instrumental broadening function. Hence, the issue of spectral decomposition is transformed into a multiparameter optimization problem of the Voigt line profile model parameters. The algorithm can eliminate instrumental broadening, obtain a recovered Raman spectrum, resolve overlapping bands, and suppress random noise simultaneously. Moreover, the recovered spectrum can be decomposed to a group of Lorentzian functions. Experimental results on simulated Raman spectra show that the performance of this algorithm is much better than a commonly used blind deconvolution method. The algorithm has also been tested on the industrial Raman spectra of ortho-xylene and proved to be effective. PMID- 27411137 TI - Feasibility of cascaded multi-dithering technique for coherent addition of a large number of beam elements. AB - The capacity of cascaded multi-dithering technique in terms of scalability is analyzed by developing equations and performing simulations whose results are found to be in agreement with the earlier experimental result of a sixteen fiber beam combination using the cascaded multi-dithering technique. PMID- 27411138 TI - Thermal refocusing method for spaceborne high-resolution optical imagers. AB - We describe the design of a thermal refocusing method for spaceborne high resolution imagers where Korsch optical design is usually implemented. The secondary mirror is made of aluminum, a high thermal expansion coefficient material, instead of conventional zero-expansion glass ceramics. In this way, the radius of the curvature can be controlled by means of temperature change of the mirror. Change in the radius of curvature also changes the effective focal length of the camera which is used for compensation of the defocus that occurred in space. We show that the 30 MUm despace of the secondary mirror in the optical system can be compensated by an ~10 degrees C temperature change of the mirror while the image quality is maintained. PMID- 27411139 TI - Frequency-tunable metamaterial absorber using a varactor-loaded fishnet-like resonator. AB - A frequency-tunable metamaterial absorber is designed with the unit cell consisting of a varactor-loaded fishnet-like resonator. This geometry allows all cathode and anode pads of the unit cells to be connected to their counterparts. Hence, only the ends of the periodic structure need to be biased, reducing the complexity of the bias network. The absorber was modeled using a full-wave simulation tool and verified experimentally with a 20*20 unit-cell prototype. Using free-space measurements, the absorber shows >90% absorption ratio from 3.96 to 5.29 GHz with a frequency tuning ratio of 28.7%, when the reverse voltage varied from 0 to 19 V. PMID- 27411140 TI - 110 W all-fiber picosecond master oscillator power amplifier based on large-core diameter ytterbium-doped fiber. AB - We demonstrate an all-fiber picosecond fiber laser in a master oscillator power amplifier configuration. The seed source is a soliton-type passively mode-locked Yb-doped fiber laser by a semiconductor saturable absorber mirror and chirped fiber Bragg grating. The pulse width of the seed laser is 4.5 ps with a repetition rate of 15 MHz. A highly doped active fiber with a large core diameter (50 MUm) is employed to boost the average power of the seed pulses to 117 W with 11 ps pulse width and 709 kW peak power. The corresponding output beam quality factor at maximum output power is 3.7. The all-fiber construction of the whole laser system enables compact size and robust operation. PMID- 27411141 TI - Image interpolation used in three-dimensional range data compression. AB - Advances in the field of three-dimensional (3D) scanning have made the acquisition of 3D range data easier and easier. However, with the large size of 3D range data comes the challenge of storing and transmitting it. To address this challenge, this paper presents a framework to further compress 3D range data using image interpolation. We first use a virtual fringe-projection system to store 3D range data as images, and then apply the interpolation algorithm to the images to reduce their resolution to further reduce the data size. When the 3D range data are needed, the low-resolution image is scaled up to its original resolution by applying the interpolation algorithm, and then the scaled-up image is decoded and the 3D range data are recovered according to the decoded result. Experimental results show that the proposed method could further reduce the data size while maintaining a low rate of error. PMID- 27411142 TI - Noncritically phase-matched fourth-harmonic generation of Nd:glass lasers and design of final optics assembly. AB - The noncritically phase-matched (NCPM) fourth-harmonic generation (FHG) with partially deuterated dihydrogen phosphate (KD*P) crystal at an Nd:glass laser radiation wavelength of 1053.1 nm has been confirmed. NCPM FHG has been achieved in 70% and 65% deuterated KD*P crystal at the temperature of 17.7 degrees C and 29.3 degrees C, respectively. The angular acceptance of 70% and 65% deuterated KD*P crystals fixed at their NCPM temperature were measured, which were 53 and 55 mrad, respectively. The application of the NCPM FHG in a high-power laser facility for inertial confinement fusion is also discussed. Based on the theoretical analysis, the NCPM KD*P can be placed after the focus lens; thus, the laser-induced damage of a fused-silica lens at ultraviolet can be avoided. PMID- 27411143 TI - Detection of defects on the surface of a semiconductor by terahertz surface plasmon polaritons. AB - We propose a new method for detecting small defects on the surface of a semiconductor by analyzing the transmission spectrum of terahertz surface plasmon polaritons. The field distributions caused by the detection of defects of different sizes are simulated. Experimentally, using a terahertz time domain spectrometer, we measure the transmission spectrum of terahertz surface plasmon polaritons passing through particles on the surface of an intrinsic InSb wafer. Our results show that the measured temporal waveform and frequency spectra are distinctly changed due to the presence of the particles, thereby confirming the effectiveness of this method for detecting defects. For increased detection efficiency, the frequency of the surface plasmon polaritons has to be slightly lower than the plasma frequency of the semiconductor. In comparison with traditional methods, our approach offers the merits of detecting both on-surface and subsurface defects, which is critical in monitoring the quality of semiconductor wafers. PMID- 27411144 TI - Polarization-maintaining low-loss porous-core spiral photonic crystal fiber for terahertz wave guidance. AB - A polarization-maintaining porous-core spiral photonic crystal fiber is proposed for efficient transmission of polarization-maintaining terahertz (THz) waves. The finite element method with perfectly matched layer boundary conditions is used to characterize the guiding properties. We demonstrate that by creating artificial asymmetry in the porous core, an ultrahigh birefringence of 0.0483 can be obtained at the operating frequency of 1.0 THz. Moreover, a low effective material loss of 0.085 cm-1 and very small confinement loss of 1.91*10-3 dB/cm are achieved for the y-polarization mode with optimal design parameters. This article also focuses on some crucial design parameters such as power fraction, bending loss, and dispersion for usability in the THz regime. PMID- 27411146 TI - Compact and efficient passively Q-switched laser at 473 nm with an Nd:YAG/YAG/Cr4+:YAG/YAG multifunctional composite crystal. AB - An Nd:YAG/YAG/Cr4+:YAG/YAG composite crystal and an LBO crystal were used to generate a passively Q-switched frequency-doubling 473 nm blue laser for the first time, to the best of our knowledge. The result demonstrated that the slope efficiency of this system reaches 18%, which is the highest in all the passively Q-switched 473 nm laser systems reported, to the best of our knowledge. Under the pumped power of 8.64 W, the maximum average output power of 0.93 W was obtained with a pulsewidth of 78 ns, and the repetition rate of 18.5 kHz. PMID- 27411145 TI - Color computer-generated hologram generation using the random phase-free method and color space conversion. AB - We propose two calculation methods of generating color computer-generated holograms (CGHs) with the random phase-free method and color space conversion in order to improve the image quality and accelerate the calculation. The random phase-free method improves the image quality in monochrome CGH, but it is not performed in color CGH. We first aimed to improve the image quality of color CGH using the random phase-free method and then to accelerate the color CGH generation with a combination of the random phase-free method and color space conversion method, which accelerates the color CGH calculation due to down sampling of the color components converted by color space conversion. To overcome the problem of image quality degradation that occurs due to the down-sampling of random phases, the combination of the random phase-free method and color space conversion method improves the quality of reconstructed images and accelerates the color CGH calculation. We demonstrated the effectiveness of the proposed method in simulation, and in this paper discuss its application to lensless zoomable holographic projection. PMID- 27411147 TI - Comparative efficiency analysis of fiber-array and conventional beam director systems in volume turbulence. AB - The performance of two prominent laser beam projection system types is analyzed through wave-optics numerical simulations for various atmospheric turbulence conditions, propagation distances, and adaptive optics (AO) mitigation techniques. Comparisons are made between different configurations of both a conventional beam director (BD) using a monolithic-optics-based Cassegrain telescope and a fiber-array BD that uses an array of densely packed fiber collimators. The BD systems considered have equal input power and aperture diameters. The projected laser beam power inside the Airy size disk at the target plane is used as the performance metric. For the fiber-array system, both incoherent and coherent beam combining regimes are considered. We also present preliminary results of side-by-side atmospheric beam projection experiments over a 7-km propagation path using both the AO-enhanced beam projection system with a Cassegrain telescope and the coherent fiber-array BD composed of 21 densely packed fiber collimators. Both wave-optics numerical simulation and experimental results demonstrate that, for similar system architectures and turbulence conditions, coherent fiber-array systems are more efficient in mitigation of atmospheric turbulence effects and generation of a hit spot of the smallest possible size on a remotely located target. PMID- 27411148 TI - Computational method for simulation of thermal load distribution in a lithographic lens. AB - As a crucial step for thermal aberration prediction, thermal simulation is an effective way to acquire the temperature distribution of lenses. In the case of rigorous thermal simulation with the finite volume method, the amount of absorbed energy and its distribution within lens elements should be provided to guarantee simulation accuracy. In this paper, a computational method for simulation of thermal load distribution concerning lens material absorption was proposed based on light intensity of lens elements' surfaces. An algorithm for the verification of the method was also introduced, and the results showed that the method presented in this paper is an effective solution for thermal load distribution in a lithographic lens. PMID- 27411149 TI - Full control of polarization state with a pair of electro-optic modulators for polarization-resolved optical microscopy: erratum. AB - In our previous paper [Appl. Opt.55, 1082 (2016)APOPAI0003 693510.1364/AO.55.001082], we presented a methodology for full control of a polarization state using a pair of electro-optic modulators. In this erratum, we correct errors in Eqs. (9b) and (9c) in the original paper. PMID- 27411150 TI - Branch and bound algorithm for accurate estimation of analytical isotropic bidirectional reflectance distribution function models. AB - We present a reliable and accurate global optimization framework for estimating parameters of isotropic analytical bidirectional reflectance distribution function (BRDF) models. This approach is based on a branch and bound strategy with linear programming and interval analysis. Conventional local optimization is often very inefficient for BRDF estimation since its fitting quality is highly dependent on initial guesses due to the nonlinearity of analytical BRDF models. The algorithm presented in this paper employs L1-norm error minimization to estimate BRDF parameters in a globally optimal way and interval arithmetic to derive our feasibility problem and lower bounding function. Our method is developed for the Cook-Torrance model but with several normal distribution functions such as the Beckmann, Berry, and GGX functions. Experiments have been carried out to validate the presented method using 100 isotropic materials from the MERL BRDF database, and our experimental results demonstrate that the L1-norm minimization provides a more accurate and reliable solution than the L2-norm minimization. PMID- 27411151 TI - Generation regimes of bidirectional hybridly mode-locked ultrashort pulse erbium doped all-fiber ring laser with a distributed polarizer. AB - We report on the stable picosecond and femtosecond pulse generation from the bidirectional erbium-doped all-fiber ring laser hybridly mode-locked with a coaction of a single-walled carbon nanotube-based saturable absorber and nonlinear polarization evolution that was introduced through the insertion of the short-segment polarizing fiber. Depending on the total intracavity dispersion value, the laser emits conservative solitons, transform-limited Gaussian pulses, or highly chirped stretched pulses with almost 20 nm wide parabolic spectrum in both clockwise (CW) and counterclockwise (CCW) directions of the ring. Owing to the polarizing action in the cavity, we have demonstrated for the first time, to the best of our knowledge, an efficient tuning of soliton pulse characteristics for both CW and CCW channels via an appropriate polarization control. We believe that the bidirectional laser presented may be highly promising for gyroscopic and other dual-channel applications. PMID- 27411152 TI - Absolute distance measurement by multi-heterodyne interferometry using a frequency comb and a cavity-stabilized tunable laser. AB - In this paper, we develop a multi-heterodyne system capable of absolute distance measurement using a frequency comb and a tunable diode laser locked to a Fabry Perot cavity. In a series of subsequent measurements, numerous beat components can be obtained by downconverting the optical frequency into the RF region with multi-heterodyne interferometry. The distances can be measured via the mode phases with a series of synthetic wavelengths. The comparison with the reference interferometer shows an agreement within 1.5 MUm for the averages of five measurements and 2.5 MUm for the single measurement, which is at the 10 8 relative precision level. PMID- 27411153 TI - Reflection and transmission properties of a metasurface composed of resonant loaded wire dipoles. AB - A considered metasurface is assumed to consist of a two-dimensional periodic arrangement of inductively loaded wires. The effects of incident angles and inductive loads upon equivalent surface impedance, reflection, and transmission properties of this metasurface have been investigated using numerical simulations. It is shown that at a particular frequency and angle, a metasurface can be cloaked for the incoming incident wave with nearly zero reflection. It is further studied that this approximate zero reflection is independent of the inductances of the inductively loaded wire dipoles. PMID- 27411154 TI - Heterodyne interferometry method for calibration of a Soleil-Babinet compensator. AB - A method based on the common-path heterodyne interferometer system is proposed for the calibration of a Soleil-Babinet compensator. In this heterodyne interferometer system, which consists of two acousto-optic modulators, the compensator being calibrated is inserted into the signal path. By using the reference beam as the benchmark and a lock-in amplifier (SR844) as the phase retardation collector, retardations of 0 and lambda (one wavelength) can be located accurately, and an arbitrary retardation between 0 and lambda can also be measured accurately and continuously. By fitting a straight line to the experimental data, we obtained a linear correlation coefficient (R) of 0.995, which indicates that this system is capable of linear phase detection. The experimental results demonstrate determination accuracies of 0.212 degrees and 0.26 degrees and measurement precisions of 0.054 degrees and 0.608 degrees for retardations of 0 and lambda, respectively. PMID- 27411155 TI - Double-pulse 2-MUm integrated path differential absorption lidar airborne validation for atmospheric carbon dioxide measurement. AB - Field experiments were conducted to test and evaluate the initial atmospheric carbon dioxide (CO2) measurement capability of airborne, high-energy, double-pulsed, 2-MUm integrated path differential absorption (IPDA) lidar. This IPDA was designed, integrated, and operated at the NASA Langley Research Center on-board the NASA B-200 aircraft. The IPDA was tuned to the CO2 strong absorption line at 2050.9670 nm, which is the optimum for lower tropospheric weighted column measurements. Flights were conducted over land and ocean under different conditions. The first validation experiments of the IPDA for atmospheric CO2 remote sensing, focusing on low surface reflectivity oceanic surface returns during full day background conditions, are presented. In these experiments, the IPDA measurements were validated by comparison to airborne flask air-sampling measurements conducted by the NOAA Earth System Research Laboratory. IPDA performance modeling was conducted to evaluate measurement sensitivity and bias errors. The IPDA signals and their variation with altitude compare well with predicted model results. In addition, off-off-line testing was conducted, with fixed instrument settings, to evaluate the IPDA systematic and random errors. Analysis shows an altitude-independent differential optical depth offset of 0.0769. Optical depth measurement uncertainty of 0.0918 compares well with the predicted value of 0.0761. IPDA CO2 column measurement compares well with model-driven, near-simultaneous air-sampling measurements from the NOAA aircraft at different altitudes. With a 10-s shot average, CO2 differential optical depth measurement of 1.0054+/-0.0103 was retrieved from a 6-km altitude and a 4-GHz on-line operation. As compared to CO2 weighted-average column dry-air volume mixing ratio of 404.08 ppm, derived from air sampling, IPDA measurement resulted in a value of 405.22+/-4.15 ppm with 1.02% uncertainty and 0.28% additional bias. Sensitivity analysis of environmental systematic errors correlates the additional bias to water vapor. IPDA ranging resulted in a measurement uncertainty of <3 m. PMID- 27411156 TI - Mode-locking pulse generation with MoS2-PVA saturable absorber in both anomalous and ultra-long normal dispersion regimes. AB - We experimentally demonstrate a stable and simple mode locked erbium doped fiber laser (EDFL) utilizing passive few-layer molybdenum disulfide (MoS2) as a saturable absorber. The MoS2 is obtained by liquid phase exfoliation before it is embedded in a polymer composite film and then inserted in the laser cavity. A stable soliton pulse train started at a low threshold pump power of 20 mW in the anomalous dispersion regime after fine-tuning the rotation of the polarization controller. The central wavelength, 3 dB bandwidth, pulse width, and repetition rate of the soliton pulses are 1574.6 nm, 9.5 nm, 790 fs, and 29.5 MHz, respectively. By inserting a 850 m long dispersion shifted fiber (DSF) in the cavity, a dissipative soliton with square pulse train is obtained in the normal dispersion regime where the operating wavelength is centered at 1567.44 nm with a 3 dB bandwidth of 19.68 nm. The dissipative soliton pulse has a pulse width of 90 ns at a low repetition rate of 231.5 kHz due to the long DSF used. These results are a contribution to the pool of knowledge in nonlinear optical properties of two-dimensional nanomaterials especially for ultrafast photonic applications. PMID- 27411157 TI - Refractive index determination by coherence scanning interferometry. AB - Coherence scanning interferometry is established as a powerful noncontact, three dimensional, metrology technique used to determine accurate surface roughness and topography measurements with subnanometer precision. The helical complex field (HCF) function is a topographically defined helix modulated by the electrical field reflectance, originally developed for the measurement of thin films. An approach to extend the capability of the HCF function to determine the spectral refractive index of a substrate or absorbing film has recently been proposed. In this paper, we confirm this new capability, demonstrating it on surfaces of silicon, gold, and a gold/palladium alloy using silica and zirconia oxide thin films. These refractive index dispersion measurements show good agreement with those obtained by spectroscopic ellipsometry. PMID- 27411158 TI - Bimodal endoscopic probe combining white-light microscopy and optical coherence tomography. AB - We present a novel bimodal endoscopic imaging probe that can simultaneously provide full-field white-light video microscopy and confocal optical coherence tomography (OCT) depth scans. The two modalities rely on spectrally separated optical paths that run partially in parallel through a micro-optical bench system, which has a cross-section of only 2 mm*2.76 mm and is realized via standard silicon micromachining techniques. With a numerical aperture of 0.061, the video modality has a resolution and field of view of 9.3 and 1240 MUm*1080 MUm, respectively. The resolution is limited by the pixel spacing of the coherent fiber bundle, which relays the acquired image from the distal to the proximal end. A custom-designed diffractive optical element placed within the video imaging path significantly improves the image contrast by up to 45% in the medium frequency range. The OCT modality is optimized for 830 nm center wavelength, and works in a confocal arrangement with an NA of 0.018. It provides single-point depth probing at the center of the video image with a lateral resolution of 20 MUm. Through its compact footprint and enhanced functionality, the probe can provide depth-resolved guiding capability for existing laparoscopes and represents a major step toward a new class of multimodal endoscopic imaging probes. PMID- 27411159 TI - Cooperative functioning between phenylalanine ammonia lyase and isochorismate synthase activities contributes to salicylic acid biosynthesis in soybean. AB - Salicylic acid (SA), an essential regulator of plant defense, is derived from chorismate via either the phenylalanine ammonia lyase (PAL) or the isochorismate synthase (ICS) catalyzed steps. The ICS pathway is thought to be the primary contributor of defense-related SA, at least in Arabidopsis. We investigated the relative contributions of PAL and ICS to defense-related SA accumulation in soybean (Glycine max). Soybean plants silenced for five PAL isoforms or two ICS isoforms were analyzed for SA concentrations and SA-derived defense responses to the hemibiotrophic pathogens Pseudomonas syringae and Phytophthora sojae. We show that, unlike in Arabidopsis, PAL and ICS pathways are equally important for pathogen-induced SA biosynthesis in soybean. Knock-down of either pathway shuts down SA biosynthesis and abrogates pathogen resistance. Moreover, unlike in Arabidopsis, pathogen infection is associated with the suppression of ICS gene expression. Pathogen-induced biosynthesis of SA via the PAL pathway correlates inversely with phenylalanine concentrations. Although infections with either virulent or avirulent strains of the pathogens increase SA concentrations, resistance protein-mediated response to avirulent P. sojae strains may function in an SA-independent manner. These results show that PAL- and ICS-catalyzed reactions function cooperatively in soybean defense and highlight the importance of PAL in pathogen-induced SA biosynthesis. PMID- 27411160 TI - Multiple faces of pain: effects of chronic pain on the brain regulation of facial expression. AB - Pain behaviors are shaped by social demands and learning processes, and chronic pain has been previously suggested to affect their meaning. In this study, we combined functional magnetic resonance imaging with in-scanner video recording during thermal pain stimulations and use multilevel mediation analyses to study the brain mediators of pain facial expressions and the perception of pain intensity (self-reports) in healthy individuals and patients with chronic back pain (CBP). Behavioral data showed that the relation between pain expression and pain report was disrupted in CBP. In both patients with CBP and healthy controls, brain activity varying on a trial-by-trial basis with pain facial expressions was mainly located in the primary motor cortex and completely dissociated from the pattern of brain activity varying with pain intensity ratings. Stronger activity was observed in CBP specifically during pain facial expressions in several nonmotor brain regions such as the medial prefrontal cortex, the precuneus, and the medial temporal lobe. In sharp contrast, no moderating effect of chronic pain was observed on brain activity associated with pain intensity ratings. Our results demonstrate that pain facial expressions and pain intensity ratings reflect different aspects of pain processing and support psychosocial models of pain suggesting that distinctive mechanisms are involved in the regulation of pain behaviors in chronic pain. PMID- 27411162 TI - Traumatic biliary neuroma after orthotopic liver transplantation: a possible cause of "unexplained" anastomotic biliary stricture. AB - BACKGROUND: Traumatic biliary neuromas (TBNs) represent a rare cause of biliary stricture (BS) after orthotopic liver transplantation (OLT). Diagnosis is challenging preoperatively and is most often made at pathology after resection. Herein, we report a 20-year experience of TBN-related BS. PATIENTS AND METHODS: Medical records of 1030 adult patients undergoing OLT from 1991 to 2014 were reviewed. Patients with histologically proven TBN were identified among those presenting a BS. RESULTS: Over the study period, 52 patients developed an anastomotic BS. Of these, 17 had repeat surgery and specimen examination identified TBN in five instances. All five patients with TBN had a duct-to-duct biliary reconstruction during OLT. Median delay from OLT to onset of symptoms was 69 months (range 4-239). Preoperative imaging showed a compressive mass in one patient. Four patients underwent TBN resection combined with hepaticojejunostomy and had an uneventful postoperative course. One patient underwent TBN resection and duct-to-duct reconstruction; he died from acute pancreatitis on postoperative day 21. After a median follow-up of 40.5 months (range 10-54), no recurrent BS occurred. CONCLUSION: Traumatic biliary neuromas represent a possible diagnosis for unexplained anastomotic BS after OLT. Surgical excision combined with hepaticojejunostomy is effective, allows histological diagnosis, and prevents from recurrence. PMID- 27411161 TI - Venous thromboembolism and subsequent permanent work-related disability. AB - : Essentials The burden of venous thromboembolism (VTE) related to permanent work related disability is unknown. In a cohort of 66 005 individuals, the risk of work-related disability after a VTE was assessed. Unprovoked VTE was associated with 52% increased risk of work-related disability. This suggests that indirect costs due to loss of work time may add to the economic burden of VTE. SUMMARY: Background The burden of venous thromboembolism (VTE) related to permanent work related disability has never been assessed among a general population. Therefore, we aimed to estimate the risk of work-related disability in subjects with incident VTE compared with those without VTE in a population-based cohort. Methods From the Tromso Study and the Nord-Trondelag Health Study (HUNT), Norway, 66 005 individuals aged 20-65 years were enrolled in 1994-1997 and followed to 31 December 2008. Incident VTE events among the study participants were identified and validated, and information on work-related disability was obtained from the Norwegian National Insurance Administration database. Cox-regression models using age as time-scale and VTE as time-varying exposure were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for sex, body mass index, smoking, education level, marital status, history of cancer, diabetes, cardiovascular disease and self-rated general health. Results During follow-up, 384 subjects had a first VTE and 9862 participants were granted disability pension. The crude incidence rate of work-related disability after VTE was 37.5 (95% CI, 29.7-47.3) per 1000 person-years, vs. 13.5 (13.2-13.7) per 1000 person years among those without VTE. Subjects with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE (HR, 1.52; 95% CI, 1.09-2.14) after multivariable adjustment, and the association appeared to be driven by deep vein thrombosis. Conclusion VTE was associated with subsequent work-related disability in a cohort recruited from the general working-age population. Our findings suggest that indirect costs because of loss of work time may add to the economic burden of VTE. PMID- 27411163 TI - Coordination Chemistry of Diiodine and Implications for the Oxidation Capacity of the Synergistic Ag(+) /X2 (X=Cl, Br, I) System. AB - The synergistic Ag(+) /X2 system (X=Cl, Br, I) is a very strong, but ill-defined oxidant-more powerful than X2 or Ag(+) alone. Intermediates for its action may include [Agm (X2 )n ](m+) complexes. Here, we report on an unexpectedly variable coordination chemistry of diiodine towards this direction: (A)Ag-I2 -Ag(A), [Ag2 (I2 )4 ](2+) (A(-) )2 and [Ag2 (I2 )6 ](2+) (A(-) )2 ?(I2 )x~0.65 form by reaction of Ag(A) (A=Al(OR(F) )4 ; R(F) =C(CF3 )3 ) with diiodine (single crystal/powder XRD, Raman spectra and quantum-mechanical calculations). The molecular (A)Ag-I2 -Ag(A) is ideally set up to act as a 2 e(-) oxidant with stoichiometric formation of 2 AgI and 2 A(-) . Preliminary reactivity tests proved this (A)Ag-I2 -Ag(A) starting material to oxidize n-C5 H12 , C3 H8 , CH2 Cl2 , P4 or S8 at room temperature. A rough estimate of its electron affinity places it amongst very strong oxidizers like MF6 (M=4d metals). This suggests that (A)Ag-I2 -Ag(A) will serve as an easily in bulk accessible, well-defined, and very potent oxidant with multiple applications. PMID- 27411164 TI - The Meta-Nudge - A Response to the Claim That the Use of Nudges During the Informed Consent Process is Unavoidable. AB - Richard Thaler and Cass Sunstein, in Nudge: Improving Decisions About Health, Wealth, and Happiness, assert that rejecting the use nudges is 'pointless' because '[i]n many cases, some kind of nudge is inevitable'. Schlomo Cohen makes a similar claim. He asserts that in certain situations surgeons cannot avoid nudging patients either toward or away from consenting to surgical interventions. Cohen concludes that in these situations (assuming surgeons believe that surgery is the best option for their patients), nudging patients toward consenting to surgical interventions is (at the very least) uncriticizable or morally permissible. I call this argument: The Unavoidability Argument. In this essay, I will respond to Cohen's use of the unavoidability argument in support of using nudges during the process of informed consent. Specifically, I argue that many so called 'unavoidable nudges' are, in fact, avoidable. Although my argument is directed toward Cohen's use of the unavoidability argument, it is applicable to the unavoidability argument more generally. PMID- 27411166 TI - Metabotropic glutamate receptor 5 responses dictate differentiation of neural progenitors to NMDA-responsive cells in fragile X syndrome. AB - Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS. Treatment with the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) prevents an abnormal clustering of DHPG-responsive cells that are responsive to activation of ionotropic receptors in mouse FXS neurospheres. MPEP also corrects morphological defects of differentiated cells and enhanced migration of neuron-like cells in mouse FXS neurospheres. Unlike in mouse neurospheres, MPEP increases the differentiation of DHPG-responsive radial glial cells as well as the subpopulation of cells responsive to both DHPG and activation of ionotropic receptors in human neurospheres. However, MPEP normalizes the FXS-specific increase in the differentiation of cells responsive only to N-methyl-d-aspartate (NMDA) present in human neurospheres. Exposure to MPEP prevents the accumulation of intermediate basal progenitors in embryonic FXS mouse brain suggesting that rescue effects of GluR5 antagonist are progenitor type-dependent and species specific differences of basal progenitors may modify effects of MPEP on the cortical development. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419 437, 2017. PMID- 27411165 TI - Functional Site Discovery in a Sulfur Metabolism Enzyme by Using Directed Evolution. AB - In human pathogens, the sulfate assimilation pathway provides reduced sulfur for biosynthesis of essential metabolites, including cysteine and low-molecular weight thiol compounds. Sulfonucleotide reductases (SRs) catalyze the first committed step of sulfate reduction. In this reaction, activated sulfate in the form of adenosine-5'-phosphosulfate (APS) or 3'-phosphoadenosine 5' phosphosulfate (PAPS) is reduced to sulfite. Gene knockout, transcriptomic and proteomic data have established the importance of SRs in oxidative stress inducible antimicrobial resistance mechanisms. In previous work, we focused on rational and high-throughput design of small-molecule inhibitors that target the active site of SRs. However, another critical goal is to discover functionally important regions in SRs beyond the traditional active site. As an alternative to conservation analysis, we used directed evolution to rapidly identify functional sites in PAPS reductase (PAPR). Four new regions were discovered that are essential to PAPR function and lie outside the substrate binding pocket. Our results highlight the use of directed evolution as a tool to rapidly discover functionally important sites in proteins. PMID- 27411167 TI - Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats. AB - Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. PMID- 27411168 TI - Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations. AB - Farber disease is a very rare autosomal recessive disease caused by mutation of ASAH1 that results in the accumulation of ceramide in various tissues. Clinical symptoms of classic Farber disease comprise painful joint deformity, hoarseness of voice, and subcutaneous nodules. Here, we describe a patient with Farber disease with atypical presentation of early onset hypotonia, sacral mass, congenital heart disease, and dysmorphic face since birth. Severe cognitive disability, failure to gain motor skills, failure to thrive, and joint contractures developed. Using whole-exome sequencing, we identified the compound heterozygote missense mutations of ASAH1 (p.R333C and p.G235R). Because of the diagnostic delay, she underwent sacral mass excision, which revealed enlarged lysosomes and zebra bodies. We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. We also discuss the clinical utility of whole-exome sequencing for diagnosis of ultra-rare diseases. (c) 2016 Wiley Periodicals, Inc. PMID- 27411169 TI - Long-term declines in an intertidal foundation species parallel shifts in community composition. AB - The earth is in the midst of a biodiversity crisis, and projections indicate continuing and accelerating rates of global changes. Future alterations in communities and ecosystems may be precipitated by changes in the abundance of strongly interacting species, whose disappearance can lead to profound changes in abundance of other species, including an increase in extinction rate for some. Nearshore coastal communities are often dependent on the habitat and food resources provided by foundational plant (e.g., kelp) and animal (e.g., shellfish) species. We quantified changes in the abundance of the blue mussel (Mytilus edulis), a foundation species known to influence diversity and productivity of intertidal habitats, over the past 40 years in the Gulf of Maine, USA, one of the fastest warming regions in the global ocean. Using consistent survey methods, we compared contemporary population sizes to historical data from sites spanning >400 km. The results of these comparisons showed that blue mussels have declined in the Gulf of Maine by >60% (range: 29-100%) at the site level since the earliest benchmarks in the 1970s. At the same time as mussels declined, community composition shifted: at the four sites with historical community data, the sessile community became increasingly algal dominated. Contemporary (2013 2014) surveys across 20 sites showed that sessile species richness was positively correlated to mussel abundance in mid to high intertidal zones. These results suggest that declines in a critical foundation species may have already impacted the intertidal community. To inform future conservation efforts, we provide a database of historical and contemporary baselines of mussel population abundance and dynamics in the Gulf of Maine. Our results underscore the importance of anticipating not only changes in diversity but also changes in the abundance and identity of component species, as strong interactors like foundation species have the potential to drive cascading community shifts. PMID- 27411170 TI - Combining biochemical with (1)H NMR-based metabolomics approach unravels the antidiabetic activity of genipin and its possible mechanism. AB - Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins. Genipin possesses a wide spectrum of biological activities including ameliorating effects on diabetes, but the definite mechanism of this effect remains unknown. To investigate the antidiabetic activities of genipin and explore the biochemical changes of serum endogenous metabolites on diabetic rats induced by alloxan, (1)H NMR spectroscopy coupled with multivariate data analysis was used to. All rats were randomly divided into six groups including negative control (NC) group, diabetic mellitus (DM) group, metformin hydrochloride group, high dose group of genipin, middle dose group of genipin and low dose group of genipin. Diabetes was induced by a single intraperitoneal injection of 120mg/kg body weight of alloxan. Serum samples were collected for the (1)H NMR-based metabolomics and clinical biochemical analysis. Daily oral administration of genipin (25, 50 and 100mg/kg body weight) and metformin hydrochloride (125mg/kg) for two weeks showed beneficial effects on blood glucose level (P<0.01). Significant differences in the metabolic profile as well as the result of biochemical parameters between the diabetic group and the control group were observed. The PLS-DA scores and corresponding loading plots demonstrated that genipin significantly restored the abnormal metabolic state. Detailed analysis of the altered metabolite levels indicated that genipin significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism and amino acid metabolism. Genipin showed the best anti-diabetic effects at a dose of 100mg/kg in rats. This finding indicates that chemical and metabolomic approaches could be powerful tools for the investigation of the biochemical changes in pathological conditions or drug treatment. PMID- 27411172 TI - Neonatal fatty acid status and cardiometabolic health at 9years. AB - BACKGROUND: Long chain polyunsaturated fatty acid (LCPUFA) status is associated with risk of cardiovascular diseases in adulthood. We previously demonstrated no effect of LCPUFA supplementation after birth on BP and anthropometrics. Little is known about the association between fatty acid status at birth and cardiometabolic health at older ages. AIM: To evaluate associations between docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in the umbilical cord and blood pressure (BP) and anthropometrics at 9years. STUDY DESIGN: Observational follow-up study. Multivariable analyses were carried out to adjust for potential confounders. SUBJECTS: 229 children who took part in a randomized controlled trial (RCT) on the effects of LCPUFA formula supplementation. OUTCOME MEASURES: BP was chosen as primary outcome; heart rate and anthropometrics as secondary outcomes. RESULTS: AA levels in the wall of the umbilical vein and artery were negatively associated with diastolic BP (B: vein -0.831, 95% CI: 1.578; -0.083, p=0.030; artery: -0.605, 95% CI: -1.200; -0.010, p=0.046). AA was not associated with systolic BP; DHA not with diastolic nor systolic BP. The AA:DHA ratio in the umbilical vein was negatively associated with diastolic BP (B: -1.738, 95% CI: -3.141; -0.335, p=0.015). Heart rate and anthropometrics were not associated with neonatal LCPUFA status. CONCLUSIONS: Higher AA levels and a higher AA:DHA ratio at birth are associated with lower diastolic BP at age 9. This suggests that the effect of LCPUFAs at early age is different from that in adults, where DHA is regarded anti-adipogenic and AA as adipogenic. PMID- 27411171 TI - An ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of hederacoside C, a drug candidate for respiratory disorder, in rat plasma. AB - Hederacoside C is a principal bioactive pharmaceutical ingredient of Hedera helix leaf extracts. H. helix extracts have long been used in folk medicine for the treatment of respiratory disorders. Currently, hederacoside C is investigated as a promising candidate for the treatment of respiratory diseases. In this study, an accurate, sensitive, rapid, and reliable bioanalytical method was developed for the determination of hederacoside C in rat plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). For sample preparation, plasma proteins were precipitated with 0.1% acetic acid in acetonitrile. Waters UPLC BEH C18 (2.1mm I.D.*100mm, 1.7MUm) column was used for chromatographic separation. A gradient elution of mobile phases consisting of 0.02% acetic acid in distilled water (solvent A) and 0.02% acetic acid in acetonitrile (solvent B) was used at a flow rate of 0.3mL/min. The multiple reaction monitoring (MRM) mode was used for mass spectrometric detection; the MRM transitions were m/z 1219.7->m/z 469.2 for hederacoside C and m/z 1108.3->m/z 221.2 for ginsenoside Rb1 (internal standard) in the negative ionization mode. A calibration curve was constructed in the range of 10-1000ng/mL. The intra- and inter-day precision and accuracy were within 5%. The developed UPLC-MS/MS method was successfully applied in a pharmacokinetic study of hederacoside C in rats. Hederacoside C was quickly but inadequately absorbed from the gastrointestinal tract of rats resulting in extremely low bioavailability and relatively slow clearance. PMID- 27411174 TI - Direct transverse load profile determination using the polarization-dependent loss spectral response of a chirped fiber Bragg grating. AB - The determination of stress profiles created by transverse loads was proved to be important in different domains, such as structural health monitoring and biomechanics, and, more specifically, in the prostheses domain. In this paper, we report an original method to estimate the transverse load profile from the polarization-dependent loss (PDL) spectrum of a chirped fiber Bragg grating (CFBG). This method makes use of the relationship between the integration of the PDL of a CFBG, and the force profile has the advantage of not requiring any iterative method to estimate the transverse load profile. The relationship linking the integration of the PDL and the force profile is demonstrated using an analytical approximation of the transmission spectrum of CFBGs. The validity of this method for the determination of non-uniform load profiles is then shown using a numerical analysis. An experimental demonstration is finally reported using a 48 mm-long CFBG subject to different step transverse load profiles. PMID- 27411175 TI - Tunable Q-switched fiber laser using zinc oxide nanoparticles as a saturable absorber. AB - Nanomaterials have ignited new interest due to their distinctive electronic, mechanical, and optical properties. Zinc oxide nanostructures are fabricated into thin film and then inserted between two fiber ferrules to act as a saturable absorber (SA). The modulation depth and insertion loss of the SA are 5% and 3.5 dB, respectively. When the ZnO-SA is incorporated into the laser cavity, a stable Q-switched pulse tunable from 1536 to 1586 nm (50 nm range) with pulse energy up to 46 nJ was observed. Our result suggests that ZnO is a promising broadband SA to generate passively Q-switched fiber lasers. PMID- 27411173 TI - Achalasia: Outcome in children. AB - BACKGROUND: Oesophageal achalasia is well-recognized but relatively rare in children, occasionally appearing as the "triple A" syndrome (with adrenal insufficiency and alacrima). Treatment modalities, as in adult practice, are not curative, often needing further interventions and spurring the search for better management. The outcome for syndromic variants is unknown. We sought to define the efficacy of treatments for children with achalasia with and without triple A syndrome. METHODS: We conducted a retrospective analysis of presentation and outcomes for 42 children with achalasia presenting over three decades to a major pediatric referral center. Long term impact of the diagnosis was assessed by questionnaire. RESULTS: We identified 42 children including six with triple A syndrome. The median overall age at diagnosis was 10.8 years and median follow-up 1593 days. Initial Heller myotomy in 17 required further interventions in 11 (65%), while initial treatment with botulinum toxin (n = 20) was ultimately followed by myotomy in 17 (85%). Ten out of 35 patients who underwent myotomy required a repeat myotomy (29%). Patients with triple A syndrome developed symptoms earlier, but had delayed diagnosis, were more underweight at diagnosis and at last follow up. Questionnaire results suggested a significant long term deleterious impact on the quality of life of children and their families. CONCLUSION: Many children with achalasia relapse after initial treatment, undergoing multiple, different procedures, despite which symptoms persist and impact on quality of life. Symptoms develop earlier in patients with triple A syndrome, but the diagnosis is delayed and this has substantial nutritional impact. PMID- 27411176 TI - Approximate solution for high-frequency Q-switched lasers. AB - A simple approximation for the energy, pulse width, and build-up time valid for high-repetition-rate Q-switched lasers is discussed. This particular regime of operation is most common in industrial applications where manufacturing time must be minimized. Limits of validity and some considerations for the choice of the most appropriate laser system for specific applications are briefly discussed. PMID- 27411177 TI - Characterization and simulation of soft gamma-ray mirrors for their use with spent fuel rods at reprocessing facilities. AB - The use of a grazing incidence optic to selectively reflect K-shell fluorescence emission and isotope-specific lines from special nuclear materials is a highly desirable nondestructive analysis method for use in reprocessing fuel environments. Preliminary measurements have been performed, and a simulation suite has been developed to give insight into the design of the x ray optics system as a function of the source emission, multilayer coating characteristics, and general experimental configurations. The experimental results are compared to the predictions from our simulation toolkit to illustrate the ray-tracing capability and explore the effect of modified optics in future measurement campaigns. PMID- 27411178 TI - Accurate calibration method for camera and projector in fringe patterns measurement system. AB - The 3D measurement system based on fringe patterns is widely applied in diverse fields. The measurement accuracy is mainly determined by camera and projector calibration accuracy. In the existing methods, the system is calibrated by a dot calibration board with traditional image process algorithms. In this paper, an improved calibration method is proposed to increase camera and projector calibration accuracy simultaneously. To this end, first, a subpixel edge detection method is proposed to improve the detection accuracy of reference features for coarse calibration; second, an iterative compensation algorithm is developed to improve the detection accuracy of the reference feature centers for fine calibration. The experimental results demonstrate that the proposed calibration method can improve the calibration accuracy and measurement accuracy. PMID- 27411179 TI - Freeform illumination optics construction following an optimal transport map. AB - We present a modified optimal transport (OT) ray-mapping approach for designing freeform illumination optics. After mapping the source intensity into a virtual irradiance distribution under stereographic projection, we employ an advanced OT map computation method with the ability to tackle nonstandard boundary conditions. Following the computed map, we construct the freeform optical surface directly from normal vectors by requiring that the chord between two adjacent points is perpendicular to the average of the two normal vectors at these two points and enforcing this relationship with a least squares method. Examples of designing freeform lenses for LED sources show that we can produce various uniform illumination patterns with high optical efficiencies. PMID- 27411180 TI - Evaluation of fiber-based tools for glass polishing using experimental and computational approaches. AB - Polymeric pad or pitch-based tools combined with loose abrasive slurries are typically used in the polishing of optical materials. In this paper, the potential of fiber-based tools to both remove material and provide high quality surface finishes on BK7 glass is explored. The potential advantage of fiber-based tools over traditional tools is their inherent compliance, which could accommodate varying workpiece surface curvatures as found in aspheres and freeforms. To evaluate the new tools, both experimental and finite element (FE) modeling approaches were taken. A FE model consisting of a single fiber engaged with the workpiece surface was used to estimate the shape and magnitude of the pressure distribution exerted by the fiber on the workpiece surface. Two different tool configurations, yielding two different Fes, predicted pressure distributions, were used to polish BK7 samples, and the material removal profiles were interferometrically measured. The resulting profiles and the predicted pressure distributions share the same v-shape. While differences in scale exist between the experimental and FE-predicted profiles, the tool generating higher material removal had the greater predicted pressure distribution, thus demonstrating the ability of the FE model to provide insights into tool design. Additional testing was conducted to determine if the tool's removal rate can be predicted by Preston's equation. Initial results indicate the equation is valid within the range of parameters tested. The surface roughness of BK7 samples processed by this tool was measured and some deterioration on the Sq value was noted; the surface roughness increased from 1.89 to 3.66 nm Sq. Over several hours of continuous use, the load applied by the fibers decays in a repeatable manner, and little wear was observed on the fibers after 5.33 h of polishing. PMID- 27411181 TI - Rigorous study of supercontinuum generation in few mode fibers. AB - We numerically studied supercontinuum (SC) generation in a few-mode photonic crystal fiber (PCF). We have shown the impact of the intermodal nonlinear effects that could limit the fundamental mode nonlinear propagation due to the coupling induced by high-order optical modes. We have demonstrated an accurate modeling of the SC generation into the multimode PCF by solving the multimode generalized nonlinear Shrodinger equation (MM-GNLSE). Our detailed investigation of the dynamics of the intermodal nonlinear effects on the SC process confirms the energy transfer between optical degenerate modes during propagation inside the few-mode PCF. PMID- 27411182 TI - Versatile mode-locked fiber laser with switchable operation states of bound solitons. AB - Bound states of two solitons are among the typical forms of bound states and can be observed in various operation states of mode-locked fiber lasers. We experimentally investigated bound solitons (BSs) in a passively mode-locked erbium-doped fiber laser based on a semiconductor saturable absorber mirror, whose operation states can be switched among multiple pulses, passively harmonic mode-locking, and "giant pulses" by simply adjusting the in-line polarization controller with the pump power fixed. Up to four pulses, fourth-order harmonic mode-locking (HML), and a "giant pulse" with four BSs were obtained with increasing pump power. Experimental results showed a correlative relationship among those operation states (N pulses/Nth-order HML/"giant pulses" of N bound solitons) at different pump power levels. The birefringence induced by the erbium doped fiber inside the laser cavity played a vital role in the transitions of those operation states. PMID- 27411183 TI - Efficient asymmetric image authentication schemes based on photon counting-double random phase encoding and RSA algorithms. AB - Recently, double random phase encoding (DRPE) has been integrated with the photon counting (PC) imaging technique for the purpose of secure image authentication. In this scheme, the same key should be securely distributed and shared between the sender and receiver, but this is one of the most vexing problems of symmetric cryptosystems. In this study, we propose an efficient asymmetric image authentication scheme by combining the PC-DRPE and RSA algorithms, which solves key management and distribution problems. The retrieved image from the proposed authentication method contains photon-limited encrypted data obtained by means of PC-DRPE. Therefore, the original image can be protected while the retrieved image can be efficiently verified using a statistical nonlinear correlation approach. Experimental results demonstrate the feasibility of our proposed asymmetric image authentication method. PMID- 27411184 TI - Efficient multibeam large-angle nonmechanical laser beam steering from computer generated holograms rendered on a liquid crystal spatial light modulator. AB - Multibeam large-angle beam steering is demonstrated in the visible spectral region by imprinting computer-generated holographic Fresnel zone plates on a liquid crystal spatial light modulator (SLM) configured as the first element of a telescope. The position and intensity of each beam are controlled independently. The laser beam is steered over a +/-37 degrees field of regard, with the power in the beam at 37 degrees being greater than 50% of the on-axis power. The power delivered on axis for a single beam was 48% of the power incident on the SLM. The beam profile remained Gaussian over the full steering range, and the on-axis beam divergence is 2.1 mrad. PMID- 27411185 TI - Graphene-based fine-tunable optical delay line for optical beamforming in phased array antennas. AB - The design of an integrated graphene-based fine-tunable optical delay line on silicon nitride for optical beamforming in phased-array antennas is reported. A high value of the optical delay time (taug=920 ps) together with a compact footprint (4.15 mm2) and optical loss <27 dB make this device particularly suitable for highly efficient steering in active phased-array antennas. The delay line includes two graphene-based Mach-Zehnder interferometer switches and two vertically stacked microring resonators between which a graphene capacitor is placed. The tuning range is obtained by varying the value of the voltage applied to the graphene electrodes, which controls the optical path of the light propagation and therefore the delay time. The graphene provides a faster reconfigurable time and low values of energy dissipation. Such significant advantages, together with a negligible beam-squint effect, allow us to overcome the limitations of conventional RF beamformers. A highly efficient fine-tunable optical delay line for the beamsteering of 20 radiating elements up to +/-20 degrees in the azimuth direction of a tile in a phased-array antenna of an X band synthetic aperture radar has been designed. PMID- 27411186 TI - Effect of incident angle and polarization on electrically-tunable defect mode in anisotropic photonic crystals. AB - In this study, the effects of incident angle and state of wave polarization on electrically-tunable defect mode in a one-dimensional photonic crystal (1DPC) structure with an anisotropic defect layer is theoretically investigated. A 4*4 transfer matrix method is employed to calculate the transmittance spectrum of the structure with biased defect layer at different incident angles for TE and TM polarizations. The results indicate that at both polarizations, the peak wavelength of the defect mode shifts toward blue as the angle of incidence increases. Also, blue and red shifts can be observed in the defect mode for positive and negative biases, respectively. In addition, the defect mode compresses at TE (TM) polarization at negative (positive) biases and broadens for positive (negative) biases. A tunability defect mode may have potential application in the design of controllable optical filters in all optoelectronic devices. PMID- 27411187 TI - Frequency difference stabilization in dual-frequency laser by stress-induced birefringence closed-loop control. AB - The frequency difference of dual-frequency lasers is increasingly becoming an area of focus in research. The stabilization of beat frequency is of significance in fields such as synthetic wavelength and shows great potential in precise measurement. In this paper, a novel device based on stress-induced birefringence closed-loop control is proposed. Experiments are carried out on a dual-frequency He-Ne Zeeman-birefringence laser with the output mirror sealed in the opposite direction. The results show that the device is capable of controlling the frequency difference variation in 1.3%, in a convenient and highly cost-effective way, and it can increase the quantity of frequency difference, which is crucial to the application of precise measurement through dual-frequency lasers. PMID- 27411188 TI - Relationship between the results of laser-induced breakdown spectroscopy and dynamical mechanical analysis in composite solid propellants during their aging. AB - Laser-induced breakdown spectroscopy (LIBS) has been used to analyze thermal aging in AP/HTPB composite solid propellants, where AP and HTPB are ammonium perchlorate and hydroxyl-terminated polybutadiene, respectively. The method of accelerated aging was used to obtain samples of different ages. Dynamical mechanical analysis results have been provided in order to validate the LIBS results. Many methods have been used for the accurate investigation of spectra. First, molecular bands, such as CN, C2, and AlO, were compared in different samples so that their intensity ratios could be considered. In order to discriminate more accurately between different sample spectra, principle component analysis (PCA) was used as a suitable chemometric method. All these results represent changes in the chemical structure due to increasing time and temperature. PMID- 27411189 TI - Development of a wafer warpage measurement technique using Moire-based method. AB - This paper reports on a novel technique for measuring wafer warpage, using the design concepts of moire shift, digital moire, autocollimator, and the scanning profiling method. The measurement system is divided into two parts: an optical moire system and a phase analysis system. The optical arrangement can be adjusted to control the projection of a linear grating image onto the surface of a wafer to be reflected back into a CCD camera. The grating image acquired by the CCD camera is used for measurement whereas a reference grating image is obtained using the digital moire method. By overlapping the two images of the measurement and the reference gratings, the corresponding moire fringes are formed. The phase of the moire fringes will change proportionally to the degree of warpage in the wafer, which can be measured by detecting variations in the phase shift of the moire fringes in the scanning profile across the surface of the entire wafer. Measurement resolution can be controlled by adjusting the pitch size of the grating or the focal length of the focusing lens, or by adjusting the angle between the images of the measurement and reference gratings. Experiment results demonstrate that the proposed method is able to achieve an angular resolution of 0.2 MUrad. As compared to the current warpage measurement techniques, the proposed method has the ability of high measurement resolution, high stability, and high flexibility. PMID- 27411190 TI - Optimization of an intraocular lens for correction of advanced corneal refractive errors. AB - Based on numerical 3D ray tracing, we propose a new procedure to optimize personalized intra-ocular lenses (IOLs). The 3D ray tracing was based on measured corneal elevation data from patients who suffered from advanced keratoconus. A mathematical shape description of the posterior IOL surface, by means of a tensor product cubic Hermite spline, was implemented. The optimized lenses provide significantly reduced aberrations. Our results include a trade-off study that suggests that it is possible to considerably reduce the aberrations with only minor perturbations of an ideal spherical lens. The proposed procedure can be applied for correction of aberrations of any optical system by modifying a single surface. PMID- 27411191 TI - Imaging quality automated measurement of image intensifier based on orthometric phase-shifting gratings. AB - A method for automatically measuring the imaging quality parameters of an image intensifier based on orthometric phase-shifting gratings (OPSG) is proposed. Two sets of phase-shifting gratings, one with a fringe direction at 45 degrees and the other at 135 degrees , are successively projected onto the input port of the image intensifier, and the corresponding deformed patterns modulated by the measured image intensifier on its output port are captured with a CCD camera. Two phases are retrieved from these two sets of deformed patterns by a phase measuring algorithm. By building the relationship between these retrieved phases, the referential fringe period can be determined accurately. Meanwhile, the distorted phase distribution introduced by the image intensifier can also be efficiently separated wherein the subtle imaging quality information can be further decomposed. Subsequently, the magnification of the image intensifier is successfully measured by fringe period self-calibration. The experimental results have shown the feasibility of the proposed method, which can automatically measure the multiple imaging quality parameters of an image intensifier without human intervention. PMID- 27411192 TI - Probing ultrafast phenomena with radially polarized light. AB - A new modality for probing ultrafast phenomena that relies on radially or azimuthally polarized probe pulses is presented. First, we describe the principle and then theoretically analyze the signals expected for different types of pump induced nonlinearities. Last, we experimentally verify the methodology by probing a pump-induced Kerr gate with a time-delayed radially polarized probe pulse. In general, we find excellent agreement between the simulated and measured results. PMID- 27411193 TI - Enhanced two-frequency phase-shifting method. AB - One of the major challenges of employing a two-frequency (or two-wavelength) phase-shifting algorithm for absolute three-dimensional shape measurement is its sensitivity to noise. Therefore, three- or more-frequency phase-shifting algorithms are often used in lieu of a two-frequency phase-shifting algorithm for applications where the noise is severe. This paper proposes a method to use geometric constraints of digital fringe projection system to substantially reduce the noise impact by allowing the use of more than one period of equivalent phase map for temporal phase unwrapping. Experiments successfully verified the enhanced performance of the proposed method without increasing the number of patterns. PMID- 27411194 TI - Adaptive step-size algorithm for Fourier beam-propagation method with absorbing boundary layer of auto-determined width. AB - Two algorithms that enhance the utility of the absorbing boundary layer are presented, mainly in the framework of the Fourier beam-propagation method. One is an automated boundary layer width selector that chooses a near-optimal boundary size based on the initial beam shape. The second algorithm adjusts the propagation step sizes based on the beam shape at the beginning of each step in order to reduce aliasing artifacts. PMID- 27411195 TI - Determination of the full scattering matrix using coherent Fourier scatterometry. AB - We demonstrate a method to obtain within an arbitrary numerical aperture (NA) the entire scattering matrix of a scatterer by using focused beam coherent Fourier scatterometry. The far-field intensities of all scattered angles within the NA of the optical system are obtained in one shot. The corresponding phases of the field are obtained by an interferometric configuration. This method enables the retrieval of the maximum available information about the scatterer from scattered far-field data contained in the given NA of the system. PMID- 27411196 TI - 87 fs pulse generation in a diode-pumped semiconductor saturable absorber mirror mode-locked Yb:YLF laser. AB - A Yb:YLF crystal has been investigated in a femtosecond oscillator pumped by two 400 mW single-mode fiber-coupled diodes emitting at 976 nm and mode locked with a semiconductor saturable absorber mirror. Almost Fourier transform-limited pulses with durations of 87 and 107 fs were demonstrated for extraordinary and ordinary polarizations, respectively. This is, to the best of our knowledge, the first demonstration of sub-100 fs pulses with Yb:YLF, and it proves the potential for ultrashort pulse generation and amplification with this material. PMID- 27411197 TI - Electro-optic mode switch based on lithium-niobate Mach-Zehnder interferometer. AB - We propose an electro-optic mode switch based on an optical waveguide Mach Zehnder interferometer fabricated with x-cut lithium niobate by the annealed proton exchange process. The device can switch between the fundamental mode and the higher-order mode with a low driving voltage. Our typical fabricated device, which has a total length of ~24 mm, shows a mode extinction ratio of ~35 dB and a 20-dB bandwidth of ~12 nm at the wavelength 1552 nm, when driven at a voltage of 1.7 V at 26 degrees C. High performance can be obtained at any wavelength in the C+L band with a driving voltage varying by no more than 3 V. The proposed mode switch is easy to fabricate and could find applications in reconfigurable mode-division-multiplexing systems. PMID- 27411198 TI - Birefringent dual-frequency laser Doppler velocimeter using a low-frequency lock in amplifier technique for high-resolution measurements. AB - A birefringent dual-frequency laser with a half-intracavity has been used to develop a laser Doppler velocimeter (LDV). The developed LDV utilizes a new signal-processing method based on a lock-in amplifier to achieve high-resolution velocity measurements and the discrimination of positive and negative velocities. Theoretical analysis and simulation results are presented. The velocity measurement experiments by using a high-precision linear stage are performed to verify the performance of the LDV. Compared with the previous dual-frequency LDVs, the average velocity resolution of the developed LDV is improved from 0.31 mm/s to 0.028 mm/s for a target without the rotational velocity. The measurement results show that our new technique can offer a powerful instrument for metrology sciences. PMID- 27411199 TI - Reflective Schmidt-Cassegrain system for large-aperture telescopes. AB - A reflective modification of the Schmidt-Cassegrain system was built and tested. Ultraviolet (UV) and soft x-ray applications are discussed. The system consists of a planoid mirror with an aspheric profile and prime concave and secondary convex spherical mirrors. Spherical aberration in a wide field of view and astigmatism are compensated by the aspheric profile of the planoid. The main parameters of the scheme are as follows: an entrance aperture of 180 mm, a focal ratio F/3.2, an angular resolution better than 3'' (corresponding to a pixel size of a back-side illuminated CCD), a field of view of +/-1.5 degrees (2omega=3 degrees ) and a flat image field with a diameter of 30.4 mm. Due to the absence of chromatic aberrations and wide field of view, the scheme is of considerable interest for hyperspectral instruments. In particular, the operating range of the instruments can be expanded into vacuum UV and UV regions. PMID- 27411200 TI - Infrared shutter using cholesteric liquid crystal. AB - In this paper, we propose an infrared light shutter device using cholesteric liquid crystals. The pitch of the device corresponds to the wavelengths of the infrared region with a strong thermal effect. This device is intended for use as a smart window to maintain an optimal indoor temperature by controlling the infrared radiation coming from the sun. The proposed cholesteric device switches between the planar state and the isotropic state by controlling the temperature using an electrically heated transparent electrode made of indium tin oxide. A window with a planar state that reflects infrared radiation would be used mainly in the summer, while the isotropic state that transmits infrared would be applied in the winter. The proposed device produced a variety of gray levels of transmittance based on the temperature, and thus it can provide the proper temperature for each user. The easy fabrication process gives it appeal as a functional device in the smart window market, and it compares favorably with previous light shutter devices. The infrared shutter is expected to be useful for next-generation window applications. PMID- 27411201 TI - Correlation coefficient measurement of the mode-locked laser tones using four wave mixing. AB - We use four-wave mixing to measure the correlation coefficient of comb tones in a quantum-dash mode-locked laser under passive and active locked regimes. We study the uncertainty in the measurement of the correlation coefficient of the proposed method. PMID- 27411203 TI - Effects of spectral parameters on the light properties of red-green-blue white light-emitting diodes. AB - Red-green-blue white light-emitting diodes (RGB-WLEDs) have great potential as commercial solid-state lighting devices, as well as visible light communication because of their high color-rendering index (CRI) and high response frequency. The quality of light of an RGB-WLED strongly depends on its spectral parameters. In this study, we fabricated RGB-WLEDs with red, blue, and green LEDs and measured the spectral power distribution (SPD). The experimental SPD is consistent with the calculated spectrum. We also measured the SPDs of LEDs with different peak wavelengths and extracted the spectral parameters, which were then used for modeling. We studied the effect of the wavelength and the full width at half-maximum (FWHM) on both the color rendering index and the luminous efficiency (LE) of the RGB-WLED using simulations. We find that the LE improves as the wavelength of the blue LED increases and the wavelength of the red LED decreases. When the wavelength of the green LED increases, the LE increases first, but later decreases. The CRI of the RGB-WLED increases with the wavelengths of the red, blue, and green LEDs first, but then decreases. The optimal wavelengths and FWHMs for maximum color-rendering and LE of the blue, green, and red LEDs are 466, 536, 606 nm; and 26.0, 34.0, and 19.5 nm, respectively. PMID- 27411202 TI - Calibration-free wavelength modulation spectroscopy: symmetry approach and residual amplitude modulation normalization. AB - This paper offers a simple, practical strategy to implement wavelength modulation spectroscopy (WMS) with a tunable diode laser. It eliminates the need to pre characterize the laser intensity parameters or make any design changes to a conventional WMS system. Consequently, sensitivity and signal strength remain the same as what can be obtained from a traditional WMS setup at low modulation amplitude. Like previously proposed calibration-free approaches, this new method also yields an absolute absorption line shape function. To recover residual amplitude modulation (RAM) contributions present in the first and second harmonic signals of WMS, we exploited their even or odd symmetric nature. We then used these isolated RAM signals to estimate the absolute line shape function, thus removing the impact of optical intensity fluctuations on measurement. We have also discussed uncertainties and noises associated with the estimated absolute line shape function and the applicability of this new method to detect several gases in the near infrared region. We used measurements of the 1650.96 nm absorption line for 1% and 8% methane concentration in the 60-100 kPa pressure range to validate the efficacy of this new RAM recovery technique and demonstrated a calibration-free system. Because this approach has minimal dependency on diode laser operating conditions, it is more robust and suitable for harsh industrial environments. PMID- 27411204 TI - Cat-eye effect reflected beam profiles of an optical system with sensor array. AB - In this paper, we propose an applicable propagation model for Gaussian beams passing through any cat-eye target instead of traditional simplification consisting of only a mirror placed at the focal plane of a lens. According to the model, the cat-eye effect of CCD cameras affected by defocus is numerically simulated. An excellent agreement of experiment results with theoretical analysis is obtained. It is found that the reflectivity distribution at the focal plane of the cat-eye optical lens has great influence on the results, while the cat-eye effect reflected beam profiles of CCD cameras show obvious periodicity. PMID- 27411205 TI - Spatially resolved scatter measurement of diffractive micromirror arrays. AB - Spatial light modulators (SLMs) support flexible system concepts in modern optics and especially phase-only SLMs such as micromirror arrays (MMAs) appear attractive for many applications. In order to achieve a precise phase modulation, which is crucial for optical performance, careful characterization and calibration of SLM devices is required. We examine an intensity-based measurement concept, which promises distinct advantages by means of a spatially resolved scatter measurement that is combined with the MMA's diffractive principle. Measurements yield quantitative results, which are consistent with measurements of micromirror roughness components, by white-light interferometry. They reveal relative scatter as low as 10-4, which corresponds to contrast ratios up to 10,000. The potential of the technique to resolve phase changes in the subnanometer range is experimentally demonstrated. PMID- 27411206 TI - Range performance of the DARPA AWARE wide field-of-view visible imager. AB - In a prior paper, we described a new imaging architecture that addresses the need for wide field-of-view imaging combined with the resolution required to identify targets at long range. Over the last two years substantive improvements have been made to the system, both in terms of the size, weight, and power of the camera as well as to the optics and data management software. The result is an overall improvement in system performance, which we demonstrate via a maritime target identification experiment. PMID- 27411207 TI - Effect of changing speckles in digital holography on measurements of static and vibratory displacements. AB - This paper presents a study of speckle effects in measurements of static and vibratory displacements by digital holography. Such effects are shown to arise from changes in speckle fields that often occur between holographic recordings. These may be between recording holograms before and after static deformations or changes in sets of holograms recorded for vibration measurement. If the images do not change between such recordings, the effects appear to be limited mainly to round-off errors. PMID- 27411208 TI - Inspection of disbonds in multilayer dissimilar metal structure using lock-in thermography. AB - This paper reports the characterization of disbonds between a steel plate and a lead plate on the surface of the lead using lock-in thermography. Based on the photothermal model, the excitation frequency of the bonding specimen with the steel plate and the lead plate is optimized. A lock-in thermography testing system is established to inspect the specimen. The Fourier transform method is used to process the infrared image sequences. To improve the signal-to-noise ratio (SNR), a fuzzy c-means (FCM) algorithm is used to process the phase matrix. The influence of number of clusters on the processing results is researched, and the optimal value of clusters number is obtained. The shearing phase technique is used to evaluate the size of the disbonds quantitatively. The measurement results of the artificial disbonds in the specimen show good agreement with the actual values. The results prove that FCM is effective in enhancing the SNR of the phase image, which makes it feasible for the quantitative determination of defect size by the shearing phase technique. PMID- 27411209 TI - Ultrasensitive, real-time trace gas detection using a high-power, multimode diode laser and cavity ringdown spectroscopy. AB - We present a simplified cavity ringdown (CRD) trace gas detection technique that is insensitive to vibration, and capable of extremely sensitive, real-time absorption measurements. A high-power, multimode Fabry-Perot (FP) diode laser with a broad wavelength range (Deltalambdalaser~0.6 nm) is used to excite a large number of cavity modes, thereby reducing the detector's susceptibility to vibration and making it well suited for field deployment. When detecting molecular species with broad absorption features (Deltalambdaabsorption?Deltalambdalaser), the laser's broad linewidth removes the need for precision wavelength stabilization. The laser's power and broad linewidth allow the use of on-axis cavity alignment, improving the signal-to-noise ratio while maintaining its vibration insensitivity. The use of an FP diode laser has the added advantages of being inexpensive, compact, and insensitive to vibration. The technique was demonstrated using a 1.1 W (lambda=400 nm) diode laser to measure low concentrations of nitrogen dioxide (NO2) in zero air. A sensitivity of 38 parts in 1012 (ppt) was achieved using an integration time of 128 ms; for single-shot detection, 530 ppt sensitivity was demonstrated with a measurement time of 60 MUs, which opens the door to sensitive measurements with extremely high temporal resolution; to the best of our knowledge, these are the highest speed measurements of NO2 concentration using CRD spectroscopy. The reduced susceptibility to vibration was demonstrated by introducing small vibrations into the apparatus and observing that there was no measurable effect on the sensitivity of detection. PMID- 27411210 TI - Can evolutionary constraints explain the rarity of nitrogen-fixing trees in high latitude forests? AB - Contents 1195 I. 1195 II. 1196 III. 1196 IV. 1200 1200 References 1200 SUMMARY: The rarity of symbiotic nitrogen (N)-fixing trees in temperate and boreal ('high latitude') forests is curious. One explanation - the evolutionary constraints hypothesis - posits that high-latitude N-fixing trees are rare because few have evolved. Here, we consider traits necessary for high-latitude N-fixing trees. We then use recent developments in trait evolution to estimate that > 2000 and > 500 species could have evolved from low-latitude N-fixing trees and high-latitude N fixing herbs, respectively. Evolution of N-fixing from nonfixing trees is an unlikely source of diversity. Dispersal limitation seems unlikely to limit high latitude N-fixer diversity. The greater number of N-fixing species predicted to evolve than currently inhabit high-latitude forests suggests a greater role for ecological than evolutionary constraints. PMID- 27411211 TI - Single-center experience of living donor liver transplantation in patients with portal vein thrombosis. AB - BACKGROUND: Portal vein thrombosis (PVT) is a relative contraindication in living donor liver transplantation (LDLT). We investigated the long-term outcome of adult patients with PVT in LDLT. METHODS: Between 2004 and 2009, 471 cases of adult LDLT were performed and 56 patients had PVT (11.8%). Thrombectomy was attempted using a modified eversion technique. We evaluated the outcome of patients with PVT according to grade and compared with no-PVT patients. RESULTS: There was no difference in terms of age, gender, Child-Pugh score, MELD score, proportion of malignance, operation time, and total amount of transfused blood. Complete thrombectomy was successful in 73.2% (41/56), partial thrombectomy in 26.8% (15/56), and one case needed jump graft for portal vein reconstruction. Among patients with partial thrombectomy, when the PV velocity was above 20 cm/s, the remnant thrombus disappeared in 46%. The rate of PV complication was statistically not different (8.9% vs 3.4%, P=.062). Five-year survival of mild PVT was 69.3%, 60.6% for severe PVT, and 80.4% for no-PVT (P=.059). CONCLUSIONS: Eversion thrombectomy by modified technique is feasible in most cases of PVT. Good long-term outcome may be expected in LDLT with PVT. PMID- 27411212 TI - Divergent Coordination Chemistry: Parallel Synthesis of [2*2] Iron(II) Grid Complex Tauto-Conformers. AB - The coordination of iron(II) ions by a homoditopic ligand L with two tridentate chelates leads to the tautomerism-driven emergence of complexity, with isomeric tetramers and trimers as the coordination products. The structures of the two dominant [Fe(II) 4 L4 ](8+) complexes were determined by X-ray diffraction, and the distinctness of the products was confirmed by ion-mobility mass spectrometry. Moreover, these two isomers display contrasting magnetic properties (Fe(II) spin crossover vs. a blocked Fe(II) high-spin state). These results demonstrate how the coordination of a metal ion to a ligand that can undergo tautomerization can increase, at a higher hierarchical level, complexity, here expressed by the formation of isomeric molecular assemblies with distinct physical properties. Such results are of importance for improving our understanding of the emergence of complexity in chemistry and biology. PMID- 27411213 TI - Comparing Different Strategies in Directed Evolution of Enzyme Stereoselectivity: Single- versus Double-Code Saturation Mutagenesis. AB - Saturation mutagenesis at sites lining the binding pockets of enzymes constitutes a viable protein engineering technique for enhancing or inverting stereoselectivity. Statistical analysis shows that oversampling in the screening step (the bottleneck) increases astronomically as the number of residues in the randomization site increases, which is the reason why reduced amino acid alphabets have been employed, in addition to splitting large sites into smaller ones. Limonene epoxide hydrolase (LEH) has previously served as the experimental platform in these methodological efforts, enabling comparisons between single code saturation mutagenesis (SCSM) and triple-code saturation mutagenesis (TCSM); these employ either only one or three amino acids, respectively, as building blocks. In this study the comparative platform is extended by exploring the efficacy of double-code saturation mutagenesis (DCSM), in which the reduced amino acid alphabet consists of two members, chosen according to the principles of rational design on the basis of structural information. The hydrolytic desymmetrization of cyclohexene oxide is used as the model reaction, with formation of either (R,R)- or (S,S)-cyclohexane-1,2-diol. DCSM proves to be clearly superior to the likewise tested SCSM, affording both R,R- and S,S selective mutants. These variants are also good catalysts in reactions of further substrates. Docking computations reveal the basis of enantioselectivity. PMID- 27411214 TI - Compartmental and Data-Based Modeling of Cerebral Hemodynamics: Nonlinear Analysis. AB - OBJECTIVE: As an extension to our study comparing a putative compartmental and data-based model of linear dynamic cerebral autoregulation (CA) and CO2-vasomotor reactivity (VR), we study the CA-VR process in a nonlinear context. METHODS: We use the concept of principal dynamic modes (PDM) in order to obtain a compact and more easily interpretable input-output model. This in silico study permits the use of input data with a dynamic range large enough to simulate the classic homeostatic CA and VR curves using a putative structural model of the regulatory control of the cerebral circulation. The PDM model obtained using theoretical and experimental data are compared. RESULTS: It was found that the PDM model was able to reflect accurately both the simulated static CA and VR curves in the associated nonlinear functions (ANFs). Similar to experimental observations, the PDM model essentially separates the pressure-flow relationship into a linear component with fast dynamics and nonlinear components with slow dynamics. In addition, we found good qualitative agreement between the PDMs representing the dynamic theoretical and experimental CO2-flow relationship. CONCLUSION: Under the modeling assumption and in light of other experimental findings, we hypothesize that PDMs obtained from experimental data correspond with passive fluid dynamical and active regulatory mechanisms. SIGNIFICANCE: Both hypothesis-based and data based modeling approaches can be combined to offer some insight into the physiological basis of PDM model obtained from human experimental data. The PDM modeling approach potentially offers a practical way to quantify the status of specific regulatory mechanisms in the CA-VR process. PMID- 27411215 TI - Orientation-Independent Catheter-Based Characterization of Myocardial Activation. AB - : Cardiac electrogram (EGM) signals and electrophysiologic (EP) characteristics derived from them such as amplitude and timing are central to the diagnosis and therapeutic management of arrhythmias. Bipolar EGMs are often used but possess polarity and shape dependence on catheter orientation contributing to uncertainty. OBJECTIVE: We describe a novel method to map cardiac activation that resolves signals into meaningful directions and is insensitive to electrode directional effects. METHODS: Multielectrode catheters that span 2- and 3-D space are used to derive local electric field (E-field) signals. A traveling wave model of local EGM propagation motivates a new "omnipolar" reference frame in which to understand EGM E-field signals and provide bipolar component EGMs aligned with these anatomic and physiologic directions. We validate the basis of this technology and determine its accuracy using a saline tank in which we simulate physiologic propagation. RESULTS: Omnipole signals from healthy tissue are nearly free of catheter orientation effects and are constrained by biophysics to consistent morphologies and thus consistent measured amplitudes and timings. Using a 3-D EP mapping system, traveling wave treatment, and omnipolar technology (OT) E-field loops, we derived a new and nearly instantaneous means to determine conduction velocity and activation direction. CONCLUSION: We describe the basis of OT and validate it with ablation and mapping catheters in a saline tank. Finally, we illustrate OT with signals from live subjects. SIGNIFICANCE: OT's novel approach with signal processing and real-time visualization allows for a newly detailed characterization of myocardial activation that is insensitive to catheter orientation. PMID- 27411216 TI - HOTS: A Hierarchy of Event-Based Time-Surfaces for Pattern Recognition. AB - This paper describes novel event-based spatio-temporal features called time surfaces and how they can be used to create a hierarchical event-based pattern recognition architecture. Unlike existing hierarchical architectures for pattern recognition, the presented model relies on a time oriented approach to extract spatio-temporal features from the asynchronously acquired dynamics of a visual scene. These dynamics are acquired using biologically inspired frameless asynchronous event-driven vision sensors. Similarly to cortical structures, subsequent layers in our hierarchy extract increasingly abstract features using increasingly large spatio-temporal windows. The central concept is to use the rich temporal information provided by events to create contexts in the form of time-surfaces which represent the recent temporal activity within a local spatial neighborhood. We demonstrate that this concept can robustly be used at all stages of an event-based hierarchical model. First layer feature units operate on groups of pixels, while subsequent layer feature units operate on the output of lower level feature units. We report results on a previously published 36 class character recognition task and a four class canonical dynamic card pip task, achieving near 100 percent accuracy on each. We introduce a new seven class moving face recognition task, achieving 79 percent accuracy.This paper describes novel event-based spatio-temporal features called time-surfaces and how they can be used to create a hierarchical event-based pattern recognition architecture. Unlike existing hierarchical architectures for pattern recognition, the presented model relies on a time oriented approach to extract spatio-temporal features from the asynchronously acquired dynamics of a visual scene. These dynamics are acquired using biologically inspired frameless asynchronous event-driven vision sensors. Similarly to cortical structures, subsequent layers in our hierarchy extract increasingly abstract features using increasingly large spatio-temporal windows. The central concept is to use the rich temporal information provided by events to create contexts in the form of time-surfaces which represent the recent temporal activity within a local spatial neighborhood. We demonstrate that this concept can robustly be used at all stages of an event-based hierarchical model. First layer feature units operate on groups of pixels, while subsequent layer feature units operate on the output of lower level feature units. We report results on a previously published 36 class character recognition task and a four class canonical dynamic card pip task, achieving near 100 percent accuracy on each. We introduce a new seven class moving face recognition task, achieving 79 percent accuracy. PMID- 27411217 TI - Extended Modality Propagation: Image Synthesis of Pathological Cases. AB - This paper describes a novel generative model for the synthesis of multi-modal medical images of pathological cases based on a single label map. Our model builds upon i) a generative model commonly used for label fusion and multi-atlas patch-based segmentation of healthy anatomical structures, ii) the Modality Propagation iterative strategy used for a spatially-coherent synthesis of subject specific scans of desired image modalities. The expression Extended Modality Propagation is coined to refer to the extension of Modality Propagation to the synthesis of images of pathological cases. Moreover, image synthesis uncertainty is estimated. An application to Magnetic Resonance Imaging synthesis of glioma bearing brains is i) validated on the training dataset of a Multimodal Brain Tumor Image Segmentation challenge, ii) compared to the state-of-the-art in glioma image synthesis, and iii) illustrated using the output of two different tumor growth models. Such a generative model allows the generation of a large dataset of synthetic cases, which could prove useful for the training, validation, or benchmarking of image processing algorithms. PMID- 27411218 TI - Repeatability and Reproducibility of a Clinically Based QUS Phantom Study and Methodologies. AB - The purpose of this study is to evaluate the repeatability and reproducibility (R&R) of quantitative ultrasound (QUS) estimates, specifically attenuation coefficient (AC) and backscatter coefficient (BSC), using the same Siemens 3000 clinical ultrasound scanner. Additionally, the purpose of this work is to detail the measurement and analysis methodology. Repeatability is closeness of agreement between measures obtained with the same method under same conditions (same sonographer and same transducer) and reproducibility is closeness of agreement between measures obtained with the same method under different conditions (different sonographers and/or different transducers). Calibrated phantoms were scanned by two sonographers using two transducers in each session for multiple sessions over a period of four months. The phantom scans occurred as part of a clinical QUS liver study in human research participants spanning a spectrum of obesity and liver disease severity. The scanner was adjusted in each participant to obtain the highest quality liver B-mode images prior to acquiring data from the phantoms for which no scanner adjustments were made. The R&R were analyzed and estimated using the unweighted sums of squares ANOVA approach by applying two random effect models. The measurement variance caused by repeatability and reproducibility is small (AC: 2.4- 3.2*10-4 [dB/cm-MHz]2; 10log10BSC: 0.23-0.27 dB2 ). The reproducibility variance is statistically significantly lower than the repeatability variance. The total R&R was not influenced by phantom properties over a wide range representing those found in liver in vivo. PMID- 27411220 TI - Single Image Super-Resolution Using a Joint GMM Method. AB - Single image super-resolution (SR) algorithms based on joint dictionaries and sparse representations of image patches have received significant attention in the literature and deliver the state-of-the-art results. Recently, Gaussian mixture models (GMMs) have emerged as favored prior for natural image patches in various image restoration problems. In this paper, we approach the single image SR problem by using a joint GMM learnt from concatenated vectors of high and low resolution patches sampled from a large database of pairs of high resolution and the corresponding low resolution images. Covariance matrices of the learnt Gaussian models capture the inherent correlations between high and low resolution patches, which are utilized for inferring high resolution patches from given low resolution patches. The proposed joint GMM method can be interpreted as the GMM analogue of joint dictionary-based algorithms for single image SR. We study the performance of the proposed joint GMM method by comparing with various competing algorithms for single image SR. Our experiments on various natural images demonstrate the competitive performance obtained by the proposed method at low computational cost. PMID- 27411219 TI - Relative Elastic Modulus Imaging Using Sector Ultrasound Data for Abdominal Applications: An Evaluation of Strategies and Feasibility. AB - We reconstruct the elastic modulus distribution for one tissue mimicking (TM) phantom and two in vivo biopsy-confirmed liver tumors using curvilinear ultrasound echo data. Spatial distribution of the relative elastic modulus values is determined by solving an inverse problem within a region of interest (ROI). This inverse problem solution requires knowledge of the ultrasonically measured displacement field in a uniform rectilinear grid to ensure that the resolution on the resultant relative elastic modulus elastogram will be uniform over the entire ROI. Taking advantage of a new speckle tracking algorithm, two different displacement tracking strategies are investigated: 1) sector-shaped ultrasound data were converted to ultrasound data on a rectilinear grid prior to speckle tracking and 2) axial and lateral displacements directly obtained from sector shaped data were converted to vertical and horizontal displacements on a rectilinear grid after speckle tracking. Compared with strain elastography (SE), TM phantom results show that relative elastic modulus imaging (REMI) using Strategy 2 provided higher contrast-to-noise ratios (>300% and 25% increases compared with SE and REMI using Strategy 1, respectively). Furthermore, in phantoms, REMI using Strategy 2 more accurately (a 1.3% difference to shear wave elastography measurements) estimated the elastic contrast ratio between the target and the background, compared with both SE (20%-25%) and REMI using Strategy 1 (4.1%). It was also observed that relative modulus elastograms were more consistent with anatomical structures visualized on corresponding B-mode images for the two in vivo liver cases. Overall, we conclude that applying REMI is feasible for abdominal organs such as the liver. Strategy 2 offered improved and consistent results for the data investigated. PMID- 27411221 TI - Estimation of Gaussian, Poissonian-Gaussian, and Processed Visual Noise and Its Level Function. AB - We propose a method for estimating the image and video noises of different types: white Gaussian (signal-independent), mixed Poissonian-Gaussian (signal dependent), or processed (non-white). Our method also estimates the noise level function (NLF) of these types. We do so by classifying image patches based on their intensity and variance in order to find homogeneous regions that best represent the noise. We assume that the noise variance is a piecewise linear function of intensity in each intensity class. To find noise representative regions, noisy (signal-free) patches are first nominated in each intensity class. Next, clusters of connected patches are weighted, where the weights are calculated based on the degree of similarity to the noise model. The highest ranked cluster defines the peak noise variance, and other selected clusters are used to approximate the NLF. The more information we incorporate, such as temporal data and camera settings, the more reliable the estimation becomes. To account for the processed noise, (i.e., remaining after in-camera processing), we consider the ratio of low-to-high-frequency energies. We address noise variations along video signals using a temporal stabilization of the estimated noise. Objective and subjective simulations demonstrate that the proposed method outperforms other noise estimation techniques, both in accuracy and speed. PMID- 27411222 TI - Robust Elastic-Net Subspace Representation. AB - Recently, finding the low-dimensional structure of high-dimensional data has gained much attention. Given a set of data points sampled from a single subspace or a union of subspaces, the goal is to learn or capture the underlying subspace structure of the data set. In this paper, we propose elastic-net subspace representation, a new subspace representation framework using elastic-net regularization of singular values. Due to the strong convexity enforced by elastic-net, the proposed method is more stable and robust in the presence of heavy corruptions compared with existing lasso-type rank minimization approaches. For discovering a single low-dimensional subspace, we propose a computationally efficient low-rank factorization algorithm, called FactEN, using a property of the nuclear norm and the augmented Lagrangian method. Then, ClustEN is proposed to handle the general case, in which the data samples are drawn from a union of multiple subspaces, for joint subspace clustering and estimation. The proposed algorithms are applied to a number of subspace representation problems to evaluate the robustness and efficiency under various noisy conditions, and experimental results show the benefits of the proposed method compared with existing methods. PMID- 27411223 TI - Low-Rank Tensor Subspace Learning for RGB-D Action Recognition. AB - RGB-D action data inherently equip with extra depth information to improve performance of action recognition compared with RGB data, and many works represent the RGB-D data as a third-order tensor containing a spatiotemporal structure and find a subspace with lower dimension. However, there are two main challenges of these methods. First, the dimension of subspace is usually fixed manually, which may not describe the samples well in the subspace. Second, preserving local information by finding the intra-class and inter-class neighbors from a manifold is highly time-consuming. In this paper, we learn a tensor subspace, whose dimension is learned automatically by low-rank learning, for RGB D action recognition. Particularly, the tensor samples are factorized to obtain three projection matrices (PMs) by Tucker Decomposition, where all the PMs are performed by nuclear norm in a close-form to obtain the tensor ranks, which are used as tensor subspace dimension. In addition, we extract the discriminant and local information from a manifold using a graph constraint. This graph preserves the local knowledge inherently, which is faster than the previous way of calculating both the intra-class and inter-class neighbors of each sample. We evaluate the proposed method on four widely used RGB-D action datasets including MSRDailyActivity3D, MSRActionPairs, MSRActionPairs skeleton, and UTKinect Action3D datasets, and the experimental results show higher accuracy and efficiency of the proposed method. PMID- 27411226 TI - Structure-guided Protein Transition Modeling with a Probabilistic Roadmap Algorithm. AB - Proteins are macromolecules in perpetual motion, switching between structural states to modulate their function. A detailed characterization of the precise yet complex relationship between protein structure, dynamics, and function requires elucidating transitions between functionally-relevant states. Doing so challenges both wet and dry laboratories, as protein dynamics involves disparate temporal scales. In this paper we present a novel, sampling-based algorithm to compute transition paths. The algorithm exploits two main ideas. First, it leverages known structures to initialize its search and define a reduced conformation space for rapid sampling. This is key to address the insufficient sampling issue suffered by sampling-based algorithms. Second, the algorithm embeds samples in a nearest-neighbor graph where transition paths can be efficiently computed via queries. The algorithm adapts the probabilistic roadmap framework that is popular in robot motion planning. In addition to efficiently computing lowest-cost paths between any given structures, the algorithm allows investigating hypotheses regarding the order of experimentally-known structures in a transition event. This novel contribution is likely to open up new venues of research. Detailed analysis is presented on multiple-basin proteins of relevance to human disease. Multiscaling and the AMBER ff14SB force field are used to obtain energetically credible paths at atomistic detail. PMID- 27411227 TI - On the Use of Knitted Antennas and Inductively Coupled RFID Tags for Wearable Applications. AB - Recent advancements in conductive yarns and fabrication technologies offer exciting opportunities to design and knit seamless garments equipped with sensors for biomedical applications. In this paper, we discuss the design and application of a wearable strain sensor, which can be used for biomedical monitoring such as contraction, respiration, or limb movements. The system takes advantage of the intensity variations of the backscattered power (RSSI) from an inductively coupled RFID tag under physical stretching. First, we describe the antenna design along with the modeling of the sheet impedance, which characterizes the conductive textile. Experimental results with custom fabricated prototypes showed good agreement with the numerical simulation of input impedance and radiation pattern. Finally, the wearable sensor has been applied for infant breathing monitoring using a medical programmable mannequin. A machine learning technique has been developed and applied to post-process the RSSI data, and the results show that breathing and non-breathing patterns can be successfully classified. PMID- 27411224 TI - Continuous Direct Current Nerve Block Using Multi Contact High Capacitance Electrodes. AB - Charge-balanced direct current (CBDC) nerve block can be used to block nerve conduction in peripheral nerves. Previous work demonstrated that the CBDC waveform could be used to achieve a 10% duty cycle of block to non-block repeatedly for at least two hours. We demonstrate that the duty cycle of this approach can be significantly increased by utilizing multiple electrode contacts and cycling the CBDC waveform between each contact in a "carousel" configuration. Using this approach, we demonstrated in an acute rat sciatic nerve preparation, that a 30% duty cycle complete block can be achieved with two contacts; and a 100% duty cycle block (>95% complete block) can be achieved with four contacts. This latter configuration utilized a 4-s block plateau, with 3 s between successive plateaus at each contact and a recharge phase amplitude that was 34% of the block amplitude. Further optimization of the carousel approach can be achieved to improve block effectiveness and minimize total electrode length. This approach may have significant clinical use in cases where a partial or complete block of peripheral nerve activity is required. In one example case, we achieved continuous block for 22 min without degradation of nerve conduction. Future study will be required to further optimize this technique and to demonstrate safety for chronic human use. PMID- 27411228 TI - State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective. AB - Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective. PMID- 27411229 TI - An Online Unsupervised Structural Plasticity Algorithm for Spiking Neural Networks. AB - In this paper, we propose a novel winner-take-all (WTA) architecture employing neurons with nonlinear dendrites and an online unsupervised structural plasticity rule for training it. Furthermore, to aid hardware implementations, our network employs only binary synapses. The proposed learning rule is inspired by spike timing-dependent plasticity but differs for each dendrite based on its activation level. It trains the WTA network through formation and elimination of connections between inputs and synapses. To demonstrate the performance of the proposed network and learning rule, we employ it to solve two-class, four-class, and six class classification of random Poisson spike time inputs. The results indicate that by proper tuning of the inhibitory time constant of the WTA, a tradeoff between specificity and sensitivity of the network can be achieved. We use the inhibitory time constant to set the number of subpatterns per pattern we want to detect. We show that while the percentages of successful trials are 92%, 88%, and 82% for two-class, four-class, and six-class classification when no pattern subdivisions are made, it increases to 100% when each pattern is subdivided into 5 or 10 subpatterns. However, the former scenario of no pattern subdivision is more jitter resilient than the later ones. PMID- 27411230 TI - Semisupervised Feature Analysis by Mining Correlations Among Multiple Tasks. AB - In this paper, we propose a novel semisupervised feature selection framework by mining correlations among multiple tasks and apply it to different multimedia applications. Instead of independently computing the importance of features for each task, our algorithm leverages shared knowledge from multiple related tasks, thus improving the performance of feature selection. Note that the proposed algorithm is built upon an assumption that different tasks share some common structures. The proposed algorithm selects features in a batch mode, by which the correlations between various features are taken into consideration. Besides, considering the fact that labeling a large amount of training data in real world is both time-consuming and tedious, we adopt manifold learning, which exploits both labeled and unlabeled training data for a feature space analysis. Since the objective function is nonsmooth and difficult to solve, we propose an iteractive algorithm with fast convergence. Extensive experiments on different applications demonstrate that our algorithm outperforms the other state-of-the-art feature selection algorithms. PMID- 27411231 TI - LSTM: A Search Space Odyssey. AB - Several variants of the long short-term memory (LSTM) architecture for recurrent neural networks have been proposed since its inception in 1995. In recent years, these networks have become the state-of-the-art models for a variety of machine learning problems. This has led to a renewed interest in understanding the role and utility of various computational components of typical LSTM variants. In this paper, we present the first large-scale analysis of eight LSTM variants on three representative tasks: speech recognition, handwriting recognition, and polyphonic music modeling. The hyperparameters of all LSTM variants for each task were optimized separately using random search, and their importance was assessed using the powerful functional ANalysis Of VAriance framework. In total, we summarize the results of 5400 experimental runs ( ~ 15 years of CPU time), which makes our study the largest of its kind on LSTM networks. Our results show that none of the variants can improve upon the standard LSTM architecture significantly, and demonstrate the forget gate and the output activation function to be its most critical components. We further observe that the studied hyperparameters are virtually independent and derive guidelines for their efficient adjustment. PMID- 27411232 TI - Causality Analysis of Inertial Body Sensors for Multiple Sclerosis Diagnostic Enhancement. AB - Inertial body sensors have emerged in recent years as an effective tool for evaluating mobility impairment resulting from various diseases, disorders, and injuries. For example, body sensors have been used in 6-min walk (6 MW) tests for multiple sclerosis (MS) patients to identify gait features useful in the study, diagnosis, and tracking of the disease. However, most studies to date have focused on features localized to the lower or upper extremities and do not provide a holistic assessment of mobility. This paper presents a causality analysis method focused on the coordination between extremities to identify subtle whole-body mobility impairment that may aid disease diagnosis. This method was developed for and utilized in an MS pilot study with 41 subjects (28 persons with MS (PwMS) and 13 healthy controls) performing 6 MW tests. Compared with existing methods, the causality analysis provided better discrimination between healthy controls and PwMS and a deeper understanding of MS disease impact on mobility. PMID- 27411233 TI - TTSA: An Effective Scheduling Approach for Delay Bounded Tasks in Hybrid Clouds. AB - The economy of scale provided by cloud attracts a growing number of organizations and industrial companies to deploy their applications in cloud data centers (CDCs) and to provide services to users around the world. The uncertainty of arriving tasks makes it a big challenge for private CDC to cost-effectively schedule delay bounded tasks without exceeding their delay bounds. Unlike previous studies, this paper takes into account the cost minimization problem for private CDC in hybrid clouds, where the energy price of private CDC and execution price of public clouds both show the temporal diversity. Then, this paper proposes a temporal task scheduling algorithm (TTSA) to effectively dispatch all arriving tasks to private CDC and public clouds. In each iteration of TTSA, the cost minimization problem is modeled as a mixed integer linear program and solved by a hybrid simulated-annealing particle-swarm-optimization. The experimental results demonstrate that compared with the existing methods, the optimal or suboptimal scheduling strategy produced by TTSA can efficiently increase the throughput and reduce the cost of private CDC while meeting the delay bounds of all the tasks. PMID- 27411234 TI - Sliding Mode Control for Discrete-Time Systems With Markovian Packet Dropouts. AB - This paper presents the design of a sliding mode controller for networked control systems subject to successive Markovian packet dropouts. This paper adopts the Gilbert-Elliott channel model to describe the temporal correlation among packet losses, and proposes an update scheme to select the assumed available states for use in a sliding mode control law. A technique used in the theory of discrete time Markov jump linear systems is applied to tackle the effect of the packet losses. This involves introducing a couple of Lyapunov functions dependent on the indicator functions of the instantaneous packet loss, and proving that the sliding mode controller is able to drive the system state trajectories into the neighborhood of the designed integral sliding surface in mean-square sense given that the corresponding Lyapunov inequalities are satisfied. The system is guaranteed thereafter to remain inside the neighborhood of the sliding surface. Simulated case studies are presented to illustrate the effectiveness of the control law. PMID- 27411235 TI - Observer-Based Event-Triggering Consensus Control for Multiagent Systems With Lossy Sensors and Cyber-Attacks. AB - In this paper, the observer-based event-triggering consensus control problem is investigated for a class of discrete-time multiagent systems with lossy sensors and cyber-attacks. A novel distributed observer is proposed to estimate the relative full states and the estimated states are then used in the feedback protocol in order to achieve the overall consensus. An event-triggered mechanism with state-independent threshold is adopted to update the control input signals so as to reduce unnecessary data communications. The success ratio of the launched attacks is taken into account to reflect the probabilistic failures of the attacks passing through the protection devices subject to limited resources and network fluctuations. The purpose of the address problem is to design an observer-based distributed controller such that the closed-loop multiagent system achieves the prescribed consensus in spite of the lossy sensors and cyber attacks. By making use of eigenvalues and eigenvectors of the Laplacian matrix, the closed-loop system is transformed into an easy-to-analyze setting and then a sufficient condition is derived to guarantee the desired consensus. Furthermore, the controller gain is obtained in terms of the solution to certain matrix inequality which is independent of the number of agents. An algorithm is provided to optimize the consensus bound. Finally, a simulation example is utilized to illustrate the usefulness of the proposed controller design scheme. PMID- 27411236 TI - Lyapunov-Based Feedback Preparation of GHZ Entanglement of $N$ -Qubit Systems. AB - The Greenberger-Horne-Zeilinger (GHZ) entangled states are a typical class of entangled states in multiparticle systems and play an important role in the applications of quantum communication and quantum computation. For a general quantum system of qubits, degenerate measurement operators are often met, which cause the convergence obstacle in the state preparation or stabilization problem. This paper first generalizes the traditional quantum state continuous reduction theory to the case of a degenerate measurement operator and chooses a measurement operator for an arbitrarily given target GHZ entangled state, then presents a state stabilization control strategy based on the Lyapunov method and achieves the feedback preparation of the target GHZ state. In our stabilization strategy, we separate the target GHZ state and all the other GHZ states that often form the equilibrium points of the closed-loop system by dividing the state space into several different regions; and formally design a switching control law between the regions, which contains the control Hamiltonians to be constructed. By analyzing the stability of the closed-loop system in the different regions, we propose a systematic method for constructing the control Hamiltonians and solve the convergence problem caused by the degenerate measurement operator. The global stability of the whole closed-loop stochastic system is strictly proved. Also, we perform some simulation experiments on a three-qubit system and prepare a three qubit GHZ entangled state. At the same time, the simulation results show the effectiveness of the switching control law and the construction method for the control Hamiltonians proposed in this paper. PMID- 27411238 TI - Medical Devices; Gastroenterology-Urology Devices; Classification of the Metallic Biliary Stent System for Benign Strictures. Final order. AB - The Food and Drug Administration (FDA) is classifying the metallic biliary stent system for benign strictures into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the metallic biliary stent system for benign strictures' classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 27411239 TI - Hospital Contributing in Organ donation Program. PMID- 27411240 TI - Characterizing driver-response relationships in marine pelagic ecosystems for improved ocean management. AB - Scientists and resource managers often use methods and tools that assume ecosystem components respond linearly to environmental drivers and human stressors. However, a growing body of literature demonstrates that many relationships are-non-linear, where small changes in a driver prompt a disproportionately large ecological response. We aim to provide a comprehensive assessment of the relationships between drivers and ecosystem components to identify where and when non-linearities are likely to occur. We focused our analyses on one of the best-studied marine systems, pelagic ecosystems, which allowed us to apply robust statistical techniques on a large pool of previously published studies. In this synthesis, we (1) conduct a wide literature review on single driver-response relationships in pelagic systems, (2) use statistical models to identify the degree of non-linearity in these relationships, and (3) assess whether general patterns exist in the strengths and shapes of non-linear relationships across drivers. Overall we found that non-linearities are common in pelagic ecosystems, comprising at least 52% of all driver-response relation- ships. This is likely an underestimate, as papers with higher quality data and analytical approaches reported non-linear relationships at a higher frequency (on average 11% more). Consequently, in the absence of evidence for a linear relationship, it is safer to assume a relationship is non-linear. Strong non linearities can lead to greater ecological and socioeconomic consequences if they are unknown (and/or unanticipated), but if known they may provide clear thresholds to inform management targets. In pelagic systems, strongly non-linear relationships are often driven by climate and trophodynamic variables but are also associated with local stressors, such as overfishing and pollution, that can be more easily controlled by managers. Even when marine resource managers cannot influence ecosystem change, they can use information about threshold responses to guide how other stressors are managed and to adapt to new ocean conditions. As methods to detect and reduce uncertainty around threshold values improve, managers will be able to better understand and account for ubiquitous non-linear relationships. PMID- 27411241 TI - Effects of urbanization on direct and indirect interactions in a tri-trophic system. AB - While effects of urbanization on species assemblages are receiving increasing attention, effects on ecological interactions remain largely unexplored. We investigated how urbanization influences the strength of direct and indirect trophic interactions in a tri- trophic system. In a field experiment including five cities and nearby farmed areas, we used potted Vicia faba plants and manipulated the presence of Megoura viciae aphids and that of naturally occurring aphid predators. When predators could access aphids, they reduced their abundance less in the urban than in the agricultural ecosystem. Compared to aphid abundance on plants without predator access, abundance on plants with predator access was 2.58 times lower in urban and 5.27 times lower in agricultural areas. This indicates that urbanization limited top-down control of aphids by predators. In both ecosystems, plant biomass was negatively affected by herbivores and positively affected by predators, but the positive indirect predator effect was weaker in cities. Compared to aphid-infested plants without predator access, plants with predator access were 1.89 times heavier in urban and 2.12 times heavier in agricultural areas. Surprisingly, differences between ecosystems regarding the indirect predator effect on plants were not explained by the differentially strong herbivore suppression. Instead, the urban environment limited plant biomass per se, thereby mitigating the scope of a positive predator effect. Our results show that urbanization can influence direct and indirect trophic interactions through effects on biotic top-down forces and on plant growth. In order to understand how urbanization affects biodiversity and ecosystem functioning, it is fundamental to not only consider species assemblages, but also species interactions. PMID- 27411242 TI - Effects of wetland plants on denitrification rates: a meta-analysis. AB - Human activity is accelerating changes in biotic communities worldwide. Predicting impacts of these changes on ecosystem services such as denitrification, a process that mitigates the consequences of nitrogen pollution, remains one of the most important challenges facing ecologists. Wetlands especially are valued as important sites of denitrification, and wetland plants are expected to have differing effects on denitrification. We present the results of a meta-analysis, conducted on 419 published estimates of denitrification in wetlands dominated by different plant species. Plants increased denitrification rates by 55% on average. This effect varied significantly among communities as defined by the dominant plant species, but surprisingly did not differ substantially among methods for measuring denitrification or among types of wetlands. We conclude that mechanistically linking functional plant traits to denitrification will be key to predicting the role of wetlands in nitrogen mitigation in a changing world. PMID- 27411243 TI - Post-fire vegetation and fuel development influences fire severity patterns in reburns. AB - In areas where fire regimes and forest structure have been dramatically altered, there is increasing concern that contemporary fires have the potential to set forests on a positive feedback trajectory with successive reburns, one in which extensive stand-replacing fire could promote more stand-replacing fire. Our study utilized an extensive set of field plots established following four fires that occurred between 2000 and 2010 in the northern Sierra Nevada, California, USA that were subsequently reburned in 2012. The information obtained from these field plots allowed for a unique set of analyses investigating the effect of vegetation, fuels, topography, fire weather, and forest management on reburn severity. We also examined the influence of initial fire severity and time since initial fire on influential predictors of reburn severity. Our results suggest that high- to moderate-severity fire in the initial fires led to an increase in standing snags and shrub vegetation, which in combination with severe fire weather promoted high-severity fire effects in the subsequent reburn. Although fire behavior is largely driven by weather, our study demonstrates that post-fire vegetation composition and structure are also important drivers of reburn severity. In the face of changing climatic regimes and increases in extreme fire weather, these results may provide managers with options to create more fire resilient ecosystems. In areas where frequent high-severity fire is undesirable, management activities such as thinning, prescribed fire, or managed wildland fire can be used to moderate fire behavior not only prior to initial fires, but also before subsequent reburns. PMID- 27411244 TI - Fire severity unaffected by spruce beetle outbreak in spruce-fir forests in southwestern Colorado. AB - Recent large and severe outbreaks of native bark beetles have raised concern among the general public and land managers about potential for amplified fire activity in western North America. To date, the majority of studies examining bark beetle outbreaks and subsequent fire severity in the U.S. Rocky Mountains have focused on outbreaks of mountain pine beetle (MPB; Dendroctonus ponderosae) in lodgepole pine (Pinus contorta) forests, but few studies, particularly field studies, have addressed the effects of the severity of spruce beetle (Dendroctonus rufipennis Kirby) infestation on subsequent fire severity in subalpine Engelmann spruce (Picea engelmannii) and subalpine fir (Abies lasiocarpa) forests. In Colorado, the annual area infested by spruce beetle outbreaks is rapidly rising, while MPB outbreaks are subsiding; therefore understanding this relationship is of growing importance. We collected extensive field data in subalpine forests in the eastern San Juan Mountains, southwestern Colorado, USA, to investigate whether a gray-stage (< 5 yr from outbreak to time of fire) spruce beetle infestation affected fire severity. Contrary to the expectation that bark beetle infestation alters subsequent fire severity, correlation and multivariate generalized linear regression analysis revealed no influence of pre-fire spruce beetle severity on nearly all field or remotely sensed measurements of fire severity. Findings were consistent across moderate and extreme burning conditions. In comparison to severity of the pre-fire beetle outbreak, we found that topography, pre-outbreak basal area, and weather conditions exerted a stronger effect on fire severity. Our finding that beetle infestation did not alter fire severity is consistent with previous retrospective studies examining fire activity following other bark beetle outbreaks and reiterates the overriding influence of climate that creates conditions conducive to large, high-severity fires in the subalpine zone of Colorado. Both bark beetle outbreaks and wildfires have increased autonomously due to recent climate variability, but this study does not support the expectation that post-beetle outbreak forests will alter fire severity, a result that has important implications for management and policy decisions. PMID- 27411245 TI - Placing invasive species management in a spatiotemporal context. AB - Invasive species are a worldwide issue, both ecologically and economically. A large body of work focuses on various aspects of invasive species control, including how to allocate control efforts to eradicate an invasive population as cost effectively as possible: There are a diverse range of invasive species management problems, and past mathematical analyses generally focus on isolated examples, making it hard to identify and understand parallels between the different contexts. In this study, we use a single spatiotemporal model to tackle the problem of allocating control effort for invasive species when suppressing an island invasive species, and for long-term spatial suppression projects. Using feral cat suppression as an illustrative example, we identify the optimal resource allocation for island and mainland suppression projects. Our results demonstrate how using a single model to solve different problems reveals similar characteristics of the solutions in different scenarios. As well as illustrating the insights offered by linking problems through a spatiotemporal model, we also derive novel and practically applicable results for our case studies. For temporal suppression projects on islands, we find that lengthy projects are more cost effective and that rapid control projects are only economically cost effective when population growth rates are high or diminishing returns on control effort are low. When suppressing invasive species around conservation assets (e.g., national parks or exclusion fences), we find that the size of buffer zones should depend on the ratio of the species growth and spread rate. PMID- 27411246 TI - Effects of habitat composition and landscape structure on worker foraging distances of five bumble bee species. AB - Bumble bees (Bombus spp.) are important pollinators of both crops and wildflowers. Their contribution to this essential ecosystem service has been threatened over recent decades by changes in land use, which have led to declines in their populations. In order to design effective conservation measures, it is important to understand the effects of variation in landscape composition and structure on the foraging activities of worker bumble bees. This is because the viability of individual colonies is likely to be affected by the trade-off between the energetic costs of foraging over greater distances and the potential gains from access to additional resources. We used field surveys, molecular genetics, and fine resolution remote sensing to estimate the locations of wild bumble bee nests and to infer foraging distances across a 20-km2 agricultural landscape in southern England, UK. We investigated five species, including the rare B. ruderatus and ecologically similar but widespread B. hortorum. We compared worker foraging distances between species and examined how variation in landscape composition and structure affected foraging distances at the colony level. Mean worker foraging distances differed significantly between species. Bombus terrestris, B. lapidarius, and B. ruderatus exhibited significantly greater mean foraging distances (551, 536, and 501 m, respectively) than B. hortorum and B. pascuorum (336 and 272 m, respectively). There was wide variation in worker foraging distances between colonies of the same species, which was in turn strongly influenced by the amount and spatial configuration of available foraging habitats. Shorter foraging distances were found for colonies where the local landscape had high coverage and low fragmentation of semi-natural vegetation, including managed agri-environmental field margins. The strength of relationships between different landscape variables and foraging distance varied between species, for example the strongest relationship for B. ruderatus being with floral cover of preferred forage plants. Our findings suggest that management of landscape composition and configuration has the potential to reduce foraging distances across a range of bumble bee species. There is thus potential for improvements in the design and implementation of landscape management options, such as agri-environment schemes, aimed at providing foraging habitat for bumble bees and enhancing crop pollination services. PMID- 27411247 TI - Identification of migratory bird flyways in North America using community detection on biological networks. AB - Migratory behavior of waterfowl populations in North America has traditionally been broadly characterized by four north-south flyways, and these flyways have been central to the management of waterfowl populations for more than 80 yr. However, previous flyway characterizations are not easily updated with current bird movement data and fail to provide assessments of the importance of specific geographical regions to the identification of flyways. Here, we developed a network model of migratory movement for four waterfowl species, Mallard (Anas platyrhnchos), Northern Pintail (A. acuta), American Green-winged Teal (A. carolinensis), and Canada Goose (Branta canadensis), in North America, using bird band and recovery data. We then identified migratory flyways using a community detection algorithm and characterized the importance of smaller geographic regions in identifying flyways using a novel metric, the consolidation factor. We identified four main flyways for Mallards, Northern Pintails, and American Green winged Teal, with the flyway identification in Canada Geese exhibiting higher complexity. For Mallards, flyways were relatively consistent through time. However, consolidation factors revealed that for Mallards and Green-winged Teal, the presumptive Mississippi flyway was potentially a zone of high mixing between other flyways. Our results demonstrate that the network approach provides a robust method for flyway identification that is widely applicable given the relatively minimal data requirements and is easily updated with future movement data to reflect changes in flyway definitions and management goals. PMID- 27411248 TI - A characterization of autumn nocturnal migration detected by weather surveillance radars in the northeastern USA. AB - Billions of birds migrate at night over North America each year. However, few studies have described the phenology of these movements, such as magnitudes, directions, and speeds, for more than one migration season and at regional scales. In this study, we characterize density, direction, and speed of nocturnally migrating birds using data from 13 weather surveillance radars in the autumns of 2010 and 2011 in the northeastern USA. After screening radar data to remove precipitation, we applied a recently developed algorithm for characterizing velocity profiles with previously developed methods to document bird migration. Many hourly radar scans contained windborne "contamination," and these scans also exhibited generally low overall reflectivities. Hourly scans dominated by birds showed nightly and seasonal patterns that differed markedly from those of low reflectivity scans. Bird migration occurred during many nights, but a smaller number of nights with large movements of birds defined regional nocturnal migration. Densities varied by date, time, and location but peaked in the second and third deciles of night during the autumn period when the most birds were migrating. Migration track (the direction to which birds moved) shifted within nights from south-southwesterly to southwesterly during the seasonal migration peaks; this shift was not consistent with a similar shift in wind direction. Migration speeds varied within nights, although not closely with wind speed. Airspeeds increased during the night; groundspeeds were highest between the second and third deciles of night, when the greatest density of birds was migrating. Airspeeds and groundspeeds increased during the fall season, although groundspeeds fluctuated considerably with prevailing winds. Significant positive correlations characterized relationships among bird densities at southern coastal radar stations and northern inland radar stations. The quantitative descriptions of broadscale nocturnal migration patterns presented here will be essential for biological and conservation applications. These descriptions help to define migration phenology in time and space, fill knowledge gaps in avian annual cycles, and are useful for monitoring long-term population trends of migrants. Furthermore, these descriptions will aid in assessing potential risks to migrants, particularly from structures with which birds collide and artificial lighting that disorients migrants. PMID- 27411249 TI - Habitat use of migratory bats killed during autumn at wind turbines. AB - The killing of large numbers of migratory bats at wind turbines is a pressing conservation problem. Even though avoidance and mitigation measures could benefit from a better knowledge of the species' migratory habits, we lack basic information about what habitats and corridors bats use during migration. We studied the isotopic niche dimensions of three bat species that are frequently killed at wind turbines in Germany: non-migratory Pipistrellus pipistrellus, mid distance migratory Nyctalus noctula, and long- distance migratory Pipistrellus nathusii. We measured stable carbon and nitrogen isotope ratios (delta13C, delta15N) in five tissues that differed in isotopic retention time (fur, wing membrane tissue, muscle, liver, blood) to shed light on the species-specific habitat use during the autumn migration period using standard ellipse areas (SEAc). Further, we used stable isotope ratios of non-exchangeable hydrogen (delta2H(K)) in fur keratin to assess the breeding origin of bats. We inferred from isotopic composition (delta13C, delta15N) of fur keratin that isotopic niche dimensions of P. nathusii was distinct from that of N. noctula and P. pipistrellus, probably because P. nathusii was using more aquatic habitats than the other two species. Isoscape origin models supported that traveled distances before dying at wind turbines was largest for P. nathusii, intermediate for N. noctula, and shortest for P. pipistrellus. Isotopic niche dimensions calculated for each sample type separately reflected the species' migratory behavior. Pipistrellus pipistrellus and N. noctula showed similar isotopic niche breadth across all tissue types, whereas SEAc values of P. nathusii increased in tissues with slow turnaround time. Isotopic data suggested that P. nathusii consistently used aquatic habitats throughout the autumn period, whereas N. noctula showed a stronger association with terrestrial habitats during autumn compared to the pre migration period. PMID- 27411250 TI - Consequences for conservation: population density and genetic effects on reproduction of an endangered lagomorph. AB - Understanding reproduction and mating systems is important for managers tasked with conserving vulnerable species. Genetic tools allow biologists to investigate reproduction and mating systems with high resolution and are particularly useful for species that are otherwise difficult to study in their natural environments. We conducted parentage analyses using 19 nuclear DNA microsatellite loci to assess the influence of population density, genetic diversity, and ancestry on reproduction, and to examine the mating system of pygmy rabbits (Brachylagus idahoensis) bred in large naturalized enclosures for the reintroduction and recovery of the endangered distinct population in central Washington, USA. Reproductive output for females and males decreased as population density and individual homozygosity increased. We identified an interaction indicating that male reproductive output decreased as genetic diversity declined at high population densities, but there was no effect at low densities. Males with high amounts (> 50%) of Washington ancestry had higher reproductive output than the other ancestry groups, while reproductive output was decreased for males with high northern Utah/Wyoming ancestry and females with high Oregon/Nevada ancestry. Females and males bred with an average of 3.8 and 3.6 mates per year, respectively, and we found no evidence of positive or negative assortative mating with regards to ancestry. Multiple paternity was confirmed in 81% of litters, and we report the first documented cases of juvenile breeding by pygmy rabbits. This study demonstrates how variation in population density, genetic diversity, and ancestry impact fitness for an endangered species being bred for conservation. Our results advance understanding of basic life history characteristics for a cryptic species that is difficult to study in the wild and provide lessons for managing populations of vulnerable species in captive and free-ranging populations. PMID- 27411251 TI - Moderation is best: effects of grazing intensity on plant--flower visitor networks in Mediterranean communities. AB - The structure of pollination networks is an important indicator of ecosystem stability and functioning. Livestock grazing is a frequent land use practice that directly affects the abundance and diversity of flowers and pollinators and, therefore, may indirectly affect the structure of pollination networks. We studied how grazing intensity affected the structure of plant-flower visitor networks along a wide range of grazing intensities by sheep and goats, using data from 11 Mediterranean plant-flower visitor communities from Lesvos Island, Greece. We hypothesized that intermediate grazing might result in higher diversity as predicted by the Intermediate Disturbance Hypothesis, which could in turn confer more stability to the networks. Indeed, we found that networks at intermediate grazing intensities were larger, more generalized, more modular, and contained more diverse and even interactions. Despite general responses at the network level, the number of interactions and selectiveness of particular flower visitor and plant taxa in the networks responded differently to grazing intensity, presumably as a consequence of variation in the abundance of different taxa with grazing. Our results highlight the benefit of maintaining moderate levels of livestock grazing by sheep and goats to preserve the complexity and biodiversity of the rich Mediterranean communities, which have a long history of grazing by these domestic animals. PMID- 27411252 TI - Optimal management of a stochastically varying population when policy adjustment is costly. AB - Ecological systems are dynamic and policies to manage them need to respond to that variation. However, policy adjustments will sometimes be costly, which means that fine-tuning a policy to track variability in the environment very tightly will only sometimes be worthwhile. We use a classic fisheries management problem, how to manage a stochastically varying population using annually varying quotas in order to maximize profit, to examine how costs of policy adjustment change optimal management recommendations. Costs of policy adjustment (changes in fishing quotas through time) could take different forms. For example, these costs may respond to the size of the change being implemented, or there could be a fixed cost any time a quota change is made. We show how different forms of policy costs have contrasting implications for optimal policies. Though it is frequently assumed that costs to adjusting policies will dampen variation in the policy, we show that certain cost structures can actually increase variation through time. We further show that failing to account for adjustment costs has a consistently worse economic impact than would assuming these costs are present when they are not. PMID- 27411253 TI - Fishery consequences of marine reserves: short-term pain for longer-term gain. AB - Marine reserves are often established in areas that support fisheries. Larval export from reserves is argued to help compensate for the loss of fishable habitat; however, previous modeling studies have focused on long-term equilibrium outcomes. We examined the transient consequences of reserve establishment for fished metapopulations, considering both a well-mixed larval pool and a spatially explicit model based on a coral trout (Plectropomus spp.) metapopulation. When fishing pressure was reallocated relative to the area protected, yields decreased initially, then recovered, and ultimately exceeded pre-reserve levels. However, recovery time was on the order of several years to decades. If fishing pressure intensified to maintain pre-reserve yields, reserves were sometimes unable to support the increased mortality and the metapopulation collapsed. This was more likely when reserves were small, or located peripherally within the metapopulation. Overall, reserves can achieve positive conservation and fishery benefits, but fisheries management complementary to reserve implementation is essential. PMID- 27411254 TI - Carbon sources and trophic relationships of ice seals during recent environmental shifts in the Bering Sea. AB - Dramatic multiyear fluctuations in water temperature and seasonal sea ice extent and duration across the Bering-Chukchi continental shelf have occurred in this century, raising a pressing ecological question: Do such environmental changes alter marine production processes linking primary producers to upper trophic level predators? We examined this question by comparing the blubber fatty acid (FA) composition and stable carbon isotope ratios of individual FA (delta13CFA) of adult ringed seals (Pusa hispida), bearded seals (Erignathus barbatus), spotted seals (Phoca largha), and ribbon seals (Histriophoca fasciata), collectively known as "ice seals," sampled during an anomalously warm, low sea ice period in 2002-2005 in the Bering Sea and a subsequent cold, high sea ice period in 2007-2010. delta13C(FA) values, used to estimate the contribution to seals of carbon derived from sea ice algae (sympagic production) relative to that derived from water column phytoplankton (pelagic production), indicated that during the cold period, sympagic production accounted for 62-80% of the FA in the blubber of bearded seals, 51-62% in spotted seals, and 21-60% in ringed seals. Moreover, the delta13CFA values of bearded seals indicated a greater incorporation of sympagic FAs during the cold period than the warm period. This result provides the first empirical evidence of an ecosystem-scale effect of a putative change in sympagic production in the Western Arctic. The FA composition of ice seals showed clear evidence of resource partitioning among ringed, bearded, and spotted seals, and little niche separation between spotted and ribbon seals, which is consistent with previous studies. Despite interannual variability, the FA composition of ringed and bearded seals showed little evidence of differences in diet between the warm and cold periods. The findings that sympagic production contributes significantly to food webs supporting ice seals, and that the contribution apparently is less in warm years with low sea ice, raise an important concern: Will the projected warming and continuing loss of seasonal sea ice in the Arctic, and the associated decline of organic matter input from sympagic production, be compensated for by pelagic production to satisfy both pelagic and benthic carbon and energy needs? PMID- 27411255 TI - Spatial patterns of plant litter in a tidal freshwater marsh and implications for marsh persistence. AB - The maintenance of marsh platform elevation under conditions of sea level rise is dependent on mineral sediment supply to marsh surfaces and conversion of above- and belowground plant biomass to soil organic material. These physical and biological processes interact within the tidal zone, resulting in elevation dependent processes contributing to marsh accretion. Here, we explore spatial pattern in a variable related to aboveground biomass, plant litter, to reveal its role in the maintenance of marsh surfaces. Plant litter persisting through the dormant season represents the more recalcitrant portion of plant biomass, and as such has an extended period of influence on ecosystem processes. We conducted a field and remote sensing analysis of plant litter height, aboveground biomass, vertical cover, and stem density (collectively termed plant litter structure) at a tidal freshwater marsh located within the Potomac River estuary, USA. LiDAR and field observations show that plant litter structure becomes more prominent with increasing elevation. Spatial patterns in litter structure exhibit stability from year to year and correlate with patterns in soil organic matter content, revealed by measuring the loss on ignition of surface sediments. The amount of mineral material embedded within plant litter decreases with increasing elevation, representing an important tradeoff with litter structure. Therefore, at low elevations where litter structure is short and sparse, the role of plant litter is to capture sediment; at high elevations where litter structure is tall and dense, aboveground litter contributes organic matter to soil development. This organic matter contribution has the potential to eclipse that of belowground biomass as the root:shoot ratio of dominant species at high elevations is low compared to that of dominant species at low elevations. Because of these tradeoffs in mineral and organic matter incorporation into soil across elevation gradients, the rate of marsh surface elevation change is remarkably consistent across elevation. Because of the role of plant litter in marsh ecosystem processes, monitoring and assessment of these dynamic geomorphic marsh landscapes might be streamlined through the measurement of plant litter structure, either via LiDAR technologies or field observation. PMID- 27411256 TI - Phylogenetic signal in diatom ecology: perspectives for aquatic ecosystems biomonitoring. AB - Diatoms include a great diversity of taxa and are recognized as powerful bioindicators in rivers. However using diatoms for monitoring programs is costly and time consuming because most of the methodologies necessitate species-level identification. This raises the question of the optimal trade-off between taxonomic resolution and bioassessment quality. Phylogenetic tools may form the bases of new, more efficient approaches for biomonitoring if relationships between ecology and phylogeny can be demonstrated. We estimated the ecological optima of 127 diatom species for 19 environmental parameters using count data from 2119 diatom communities sampled during eight years in eastern France. Using uni- and multivariate analyses, we explored the relationships between freshwater diatom phylogeny and ecology (i.e., the phylogenetic signal). We found a significant phylogenetic signal for many of the ecological optima that were tested, but the strength of the signal varied significantly from one trait to another. Multivariate analysis also showed that the multidimensional ecological niche of diatoms can be strongly related to phylogeny. The presence of clades containing species that exhibit homogeneous ecology suggests that phylogenetic information can be useful for aquatic biomonitoring. This study highlights the presence of significant patterns of ecological optima for freshwater diatoms in relation to their phylogeny. These results suggest the presence of a signal above the species level, which is encouraging for the development of simplified methods for biomonitoring survey. PMID- 27411257 TI - Measuring spatial variation in secondary production and food quality using a common consumer approach in Lake Erie. AB - Lake Erie is a large lake straddling the border of the USA and Canada that has become increasingly eutrophic in recent years. Eutrophication is particularly focused in the shallow western basin. The western basin of Lake Erie is hydrodynamically similar to a large estuary, with riverine inputs from the Detroit and Maumee Rivers mixing together and creating gradients in chemical and physical conditions. This study was driven by two questions: (1) How does secondary production and food quality for consumers vary across this large mixing zone? and (2) Are there correlations between cyanobacterial abundance and secondary production or food quality for consumers? Measuring spatial and temporal variation in secondary production and food quality is difficult for a variety of logistical reasons, so here a common consumer approach was used. In a common consumer approach, individuals of a single species are raised under similar conditions until placed in the field across environmental gradients of interest. After some period of exposure, the response of that common consumer is measured to provide an index of spatial variation in conditions. Here, a freshwater mussel (Lampsilis siliquoidea) was deployed at 32 locations that spanned habitat types and a gradient in cyanobacterial abundance in the western basin of Lake Erie to measure spatial variation in growth (an index of secondary production) and fatty acid (FA) content (an index of food quality). We found secondary production was highest within the Maumee river mouth and lowest in the open waters of the lake. Mussel tissues in the Maumee river mouth also included more eicosapentaenoic and docosapentaenoic fatty acids (EPA and DPA, respectively), but fewer bacterial FAs, suggesting more algae at the base of the food web in the Maumee river mouth compared to open lake sites. The satellite derived estimate of cyanobacterial abundance was not correlated to secondary production, but was positively related to EPA and DPA content in the mussels, suggesting more of these important FAs in locations with more cyanobacteria. These results suggest that growth of secondary consumers and the availability of important fatty acids in the western basin are centered on the Maumee river mouth. PMID- 27411258 TI - Determining the causes behind the collapse of a small pelagic fishery using Bayesian population modeling. AB - Small pelagic fish species present complex dynamics that challenge population biologists and prevent effective management. Huge fluctuations in abundance have traditionally been associated with external environmental forcing on recruitment, exempting other processes from contributing to fisheries collapse. On the other hand, theory predicts that density dependence and overexploitation can increase the likelihood of population oscillations. Here, we combined nonlinear population modeling with Bayesian analysis to examine the importance of different regulatory mechanisms on the collapse of European anchovy (Engraulis encrasicolus) in the Bay of Biscay. The approach relied on detailed population data and in a careful characterization of changes in the environment experienced by anchovy early stages based mainly on satellite remote sensing. Alternative hypotheses about external forcing on recruitment determined prediction skill and provided alternative interpretations of the causes behind the collapse. Density dependence was weak and unable to generate huge oscillations. Instead, models considering changes in phytoplankton phenology or in larval drift presented the best prediction skill. Nevertheless, an extensive surrogate analysis showed that environmental fluctuations alone barely explain anchovy collapse without considering the impact of fishing. Our results highlight the effectiveness of a Bayesian approach to analyze the dynamics and collapse of managed populations. PMID- 27411259 TI - Stochastic life history modeling for managing regional-scale freshwater fisheries: an experimental study of brook trout. AB - Environmental heterogeneity can combine with evolutionary responses to create very dynamic and often locally independent populations across a landscape. Such complexity creates difficulties for managers trying to conserve populations across large areas. This study develops, applies, and tests the use of stochastic life history modeling and Monte Carlo simulation to assess management scenarios related to the realities of regional fisheries management and conservation. We apply this approach to the management of recreational brook trout (Salvelinus fontinalis) fishing; an activity that can severely impact species balance, abundance, and the size structure of fish communities. Specifically, the model incorporates population-specific life-history information (e.g., growth rate, reproductive effort, and survival) to allow forecasts of the impact of various management strategies and/or changes to environmental conditions on a population's ecological characteristics (e.g., size structure, abundance, and probability of persistence). Sampling was carried out in 16 water bodies spread across four sites in Atlantic Canada. Each water body was sampled in 2005 and reassessed in 2008. This sampling had two primary objectives: (1) define a significant proportion of life-history variation of brook trout in Atlantic Canada, and (2) to test the precision and accuracy of model predictions of population responses to experimental exploitation and management changes. The model successfully predicted population responses to changes in adult survival in 12 of 13 populations having sufficient data for validation testing, while also proving to be a useful tool when engaging stakeholders regarding management options and their associated risk. We suggest that such models are cost-effective and have great potential for informing proactive management of jurisdictions with numerous and diverse populations. PMID- 27411260 TI - Chronic nitrogen deposition alters tree allometric relationships: implications for biomass production and carbon storage. AB - As increasing levels of nitrogen (N) deposition impact many terrestrial ecosystems, understanding the potential effects of higher N availability is critical for forecasting tree carbon allocation patterns and thus future forest productivity. Most regional estimates of forest biomass apply allometric equations, with parameters estimated from a limited number of studies, to forest inventory data (i.e., tree diameter). However most of these allometric equations cannot account for potential effects of increased N availability on biomass allocation patterns. Using 18 yr of tree diameter, height, and mortality data collected for a dominant tree species (Acer saccharum) in an atmospheric N deposition experiment, we evaluated how greater N availability affects allometric relationships in this species. After taking into account site and individual variability, our results reveal significant differences in allometric parameters between ambient and experimental N deposition treatments. Large trees under experimental N deposition reached greater heights at a given diameter; moreover, their estimated maximum height (mean +/- standard deviation: 33.7 +/- 0.38 m) was significantly higher than that estimated under the ambient condition (31.3 +/- 0.31 m). Within small tree sizes (5-10 cm diameter) there was greater mortality under experimental N deposition, whereas the relative growth rates of small trees were greater under experimental N deposition. Calculations of stemwood biomass using our parameter estimates for the diameter-height relationship indicated the potential for significant biases in these estimates (~2.5%), with under predictions of stemwood biomass averaging 4 Mg/ha lower if ambient parameters were to be used to estimate stem biomass of trees in the experimental N deposition treatment. As atmospheric N deposition continues to increase into the future, ignoring changes in tree allometry will contribute to the uncertainty associated with aboveground carbon storage estimates across a forest with a large geographic distribution in eastern North America. PMID- 27411261 TI - Do biomass harvesting guidelines influence herpetofauna following harvests of logging residues for renewable energy?. AB - Forests are a major supplier of renewable energy; however, gleaning logging residues for use as woody biomass feedstock could negatively alter habitat for species dependent on downed wood. Biomass Harvesting Guidelines (BHGs) recommend retaining a portion of woody biomass on the forest floor following harvest. Despite BHGs being developed to help ensure ecological sustainability, their contribution to biodiversity has not been evaluated experimentally at operational scales. We compared herpetofauanal evenness, diversity, and richness and abundance of Anaxyrus terrestris and Gastrophryne carolinensis among six treatments that varied in volume and spatial arrangement of woody biomass retained after clearcutting loblolly pine (Pinus taeda) plantations in North Carolina, USA (n = 4), 2011-2014 and Georgia (n = 4), USA 2011-2013. Treatments were: (1) biomass harvest with no BHGs, (2) 15% retention with biomass clustered, (3) 15% retention with biomass dispersed, (4) 30% retention with biomass clustered, (5) 30% retention with biomass dispersed, and (6) no biomass harvest. We captured individuals with drift fence arrays and compared evenness, diversity, and richness metrics among treatments with repeated-measure, linear mixed-effects models. We determined predictors of A. terrestris and G. carolinensis abundances using a priori candidate N-mixture models with woody biomass volume, vegetation structure, and groundcover composition as covariates. We had 206 captures of 25 reptile species and 8710 captures of 17 amphibian species during 53690 trap nights. Herpetofauna diversity, evenness, and richness were similar among treatments. A. terrestris abundance was negatively related to volume of retained woody biomass in treatment units in North Carolina in 2013. G. carolinensis abundance was positively related with volume of retained woody debris in treatment units in Georgia in 2012. Other relationships between A. terrestris and G. carolinensis abundances and habitat metrics were weak or absent. The lack of consistent community or population responses suggests the addition of a woody biomass harvest to a clearcut in pine plantations does not impact herpetofauna use of Coastal Plain loblolly plantations in the southeastern United States. We recommend additional research to examine relationships between woody biomass harvesting and rarer species or amphibians with high desiccation risk, particularly in other regions and harvesting systems. PMID- 27411262 TI - Restoration treatments in urban park forests drive long-term changes in vegetation trajectories. AB - Municipalities are turning to ecological restoration of urban forests as a measure to improve air quality, ameliorate urban heat island effects, improve storm water infiltration, and provide other social and ecological benefits. However, community dynamics following urban forest restoration treatments are poorly documented. This study examines the long-term effects of ecological restoration undertaken in New York City, New York, USA, to restore native forest in urban park natural areas invaded by woody non-native plants that are regional problems. In 2009 and 2010, we sampled vegetation in 30 invaded sites in three large public parks that were restored 1988-1993, and 30 sites in three large parks that were similarly invaded but had not been restored. Data from these matched plots reveal that the restoration treatment achieved its central goals. After 15-20 years, invasive species removal followed by native tree planting resulted in persistent structural and compositional shifts, significantly lower invasive species abundance, a more complex forest structure, and greater native tree recruitment. Together, these findings indicate that successional trajectories of vegetation dynamics have diverged between restored forests and invaded forests that were not restored. In addition, the data suggest that future composition of these urban forest patches will be novel assemblages. Restored and untreated sites shared a suite of shade-intolerant, quickly-growing tree species that colonize disturbed sites, indicating that restoration treatments created sites hospitable for germination and growth of species adapted to high light conditions and disturbed soils. These findings yield an urban perspective on the use of succession theory in ecological restoration. Models of ecological restoration developed in more pristine environments must be modified for use in cities. By anticipating both urban disturbances and ecological succession, management of urban forest patches can be adjusted to better predict and direct long-term outcomes. An urban approach to ecological restoration must use realistic, flexible targets to preserve and enhance urban biodiversity for both short-term benefits and long-term sustainability. PMID- 27411263 TI - [EFFECTIVENESS OF BONE GRAFTING THROUGH WINDOWING AT FEMORAL HEAD-NECK JUNCTION FOR TREATMENT OF OSTEONECROSIS WITH SEGMENTAL COLLAPSE OF FEMORAL HEAD]. AB - OBJECTIVE: To analyze the effectiveness of bone grafting through windowing at the femoral head-neck junction for the treatment of osteonecrosis with the segmental collapse of the femoral head. METHODS: The clinical data were retrospectively analyzed from 106 patients (131 hips) with osteonecrosis with the segmental collapse of the femoral head who underwent bone grafting through windowing at the femoral head-neck junction between March 2011 and December 2013. There were 78 males and 28 females, with an average age of 31.3 years (range, 17-43 years). The body mass index ranged from 16.5 to 36.5 (mean, 24.2). There were 53 cases of corticosteroid-induced osteonecrosis of the femoral head (ONFH), 18 cases of alcohol-induced ONFH, and 35 cases of idiopathic ONFH. According to Association Research Circulation Osseous (ARCO) classification system, 105 hips were rated as stage IIIa, and 26 hips as stage IIIb; according to the China-Japan Friendship Hospital (CJFH) classification system, 41 hips were classified as C+L1 type, 13 hips as L2 type, and 77 hips as L3 type. Harris score was used for the effectiveness evaluation. The clinical failure cases were defined as patients who need total hip arthroplasty, or had a Harris score of less than 70 points. The Cox risk model analysis and Kaplan-Meier survival curves were used for multivariate analysis and univariate analysis. RESULTS: The average follow-up period was 27.9 months (range, 4-51 months). Solid fusions of bone graft were observed at 1.0-1.5 years after operation. The Harris score at last follow-up was 81.41 +/-11.93, showing significant difference when compared with preoperative score (63.24 +/- 9.98) (t = 13.710, P = 0.000). The results were excellent in 5 hips, good in 41 hips, fair in 57 hips, and poor in 28 hips, with an excellent and good rate of 35.1%. Thirty-three hips were classified as clinical failure. A progressive collapse of the femoral head was observed in 22 hips. The single factor analysis showed that preoperative ARCO stage, preoperative CJFH type, and preoperative Harris hip score were risk factors for clinical failure (P<0.05). The Cox risk model showed that ARCO stage IIIb was independent risk factor for clinical failure (P < 0.05). The Kaplan- Meier survival curves showed that ARCO stage IIIa patients had a better effectiveness than ARCO stage IIIb patients. CONCLUSION: Bone grafting through windowing at the femoral head-neck junction has a good effectiveness in patients at ARCO stage IIIa, while patients at ARCO stage IIIb and patients of CJFH types L2 and L3 have high clinical failure rates. PMID- 27411264 TI - [CLINICAL OBSERVATION OF Othofix PERTROCHANTERIC FIXATOR FOR FIXATION OF INTERTROCHANTERIC FRACTURE]. AB - OBJECTIVE: To evaluate the effectiveness of Othofix pertrochanteric fixator for fixation of intertrochanteric fracture. METHODS: A retrospective analysis was made on the clinical data from 36 cases of intertrochanteric fracture treated with Othofix pertrochanteric fixator (OPF group) and 47 cases treated with Gamma nail (Gamma group) between October 2012 and March 2015. There was no significant difference in gender, age, cause of injury, side, AO fracture classification, combined medical disease, and injury to operation time between 2 groups (P > 0.05). The operation time, intraoperative blood loss, hospitalization time, fracture union time, and complication rate were recorded and compared between 2 groups. Hip function was evaluated with Sanders post-trauma criteria. RESULTS: The operation time, intraoperative blood loss, and hospitalization time of the OPF group were significantly less than those of the Gamma group (P<0.05). All the cases were followed up 6-12 months (mean, 8.8 months) in 2 groups. Healing of incision by first intention was obtained. Bone union was achieved in 2 groups, and the fracture union time of the OPF group was significantly shorter than that of the Gamma group (t = 14.780, P = 0.000). There was no deep wound or pin track infection in 2 groups. Superficial skin reactions developed around the screw and the pins in 14 cases (38.9%) of the OPF group, but no incision infection in the Gamma group, showing significant difference (chi2 = 22.010, P = 0.001). Mild varus of the hip and pin cutting-out occurred in 3 cases (8.3%) and 2 cases (5.6%) of the OPF group, and in 4 cases (8.5%) and 3 cases (6.4%) of Gamma group, showing no significant difference (chi2 = 0.001, P = 0.960; chi2 = 0.025, P = 0.830). According to Sanders post-trauma criteria, the results were excellent in 16 cases, good in 15 cases, fair in 3 cases, and poor in 2 cases, with an excellent and good rate of 86.1% in the OPF group; the results were excellent in 22 cases, good in 20 cases, fair in 4 cases, and poor in 1 case, with an excellent and good rate of 89.4% in the Gamma group; and there was no significant difference (chi2 = 0.200, P = 0.610). CONCLUSION: The Othofix pertrochanteric fixator has good effectiveness in the treatment of intertrochanteric fracture, which has the advantages of simple operation, less operation time, little bleeding, and early functional recovery. PMID- 27411265 TI - [EFFECTIVENESS OF HIGH TIBIAL OSTEOTOMY ASSISTED BY THREE- DIMENSIONAL PRINTING TECHNOLOGY FOR CORRECTION OF VARUS KNEE WITH OSTEOARTHRITIS]. AB - OBJECTIVE: To evaluate the effectiveness of high tibial osteotomy (HTO) assisted by three-dimensional (3-D) printing technology for correction of varus knee with osteoarthritis. METHODS: Between January 2014 and June 2015, 16 patients (20 knees) with varus knee and osteoarthritis underwent HTO assisted by 3-D printing technology; a locking compression plate was used for internal fixation after HTO. There were 6 males and 10 females, aged 30-60 years (mean, 45.5 years). The disease duration was 1-10 years (mean, 6.2 years). The unilateral knee was involved in 12 cases and bilateral knees in 4 cases. According to Koshino's staging system, 3 knees were classified as stage I, 7 knees as stage II, 8 knees as stage III, and 2 knees as stage IV. Preoperative Hospital for Special Surgery (HSS) knee score was 63.8 +/- 2.2; the femorotibial angle was (184.8 +/- 2.9) degrees ; and Insall-Salvati index was 1.03 +/- 0.13. RESULTS: All the wounds healed primarily, and no complication of infection, osteofacial compartment syndrom, or deep vein thrombosis was observed. All patients were followed up 6-18 months (mean, 12.6 months). Personal paralysis was observed in 1 case (1 knee), and was cured after expectant treatment. Bone union time was 2.7-3.4 months (mean, 2.9 months). At 6 months after operation, the femorotibial angle was (173.8 +/- 2.0) degrees , showing significant difference when compared with preoperative one (t = 11.70, P = 0.00); Insall-Salvati index was 1.04 +/- 0.12, showing no significant difference when compared with preoperative one (t = -0.20, P = 0.85); and HSS knee score was significantly increased to 88.9 +/- 3.1 (t = 25.44, P = 0.00). At last follow-up, the results were excellent in 13 knees, good in 6 knees, fair in 1 knee, and the excellent and good rate was 95%. CONCLUSION: 3-D printing cutting block can greatly improve the accuracy of HTO, avoid repeated X-ray and multiple osteotomy, shorten the operation time, and ensure better effectiveness for correction of varus knee with osteoarthritis. PMID- 27411267 TI - [HEMOSTASIS EFFECT OF COMPRESSION DRESSING THERAPY AFTER TOTAL HIP ARTHROPLASTY]. AB - OBJECTIVE: To investigate the hemostasis effect of compression dressing therapy after total hip arthroplasty (THA). METHODS: Thirty-four patients undergding unilateral THA between December 2014 and March 2015 were randomly divided into observation group (compression dressing group, n = 17) and control group (ordinary dressing group, n = 17). There was no significant difference in gender, age, height, weight, lesion hips, pathogeny, disease duration, and preoperative hemoglobin between 2 groups (P > 0.05). The total blood loss theoretical value, the postoperative drainage volume, the visible blood loss, the hidden blood loss, the total blood transfusion volume, the number of patients receiving blood transfusion, and the related complications were compared between 2 groups. RESULTS: No significant difference was found in operation time and hospitalization time between 2 groups (t = 0.337, P = 0.738; t = 0.140, P = 0.889). The incisions healed by first intention in all patients. Six cases had incision subcutaneous hematoma in the control group, no incision subcutaneous hematoma occurred in the observation group (chi2 = 7.286, P = 0.018). No postoperative complications of wound superficial infection and venous thrombosis occurred in 2 groups. After operation, blood transfusion was given in 1 case of observation group and 7 cases of control group, showing significant difference (chi2 = 5.885, P = 0.039), and the total blood transfusion volume was 600 mL and 3 200 mL, respectively. There was no significant difference in preoperative blood volume and intraoperative blood loss between 2 groups (P>0.05), but the total blood loss theoretical value, the postoperative drainage volume, the visible blood loss, and the hidden blood loss in observation group were significantly less than those in control group (P < 0.05). CONCLUSION: The compression dressing should be performed after THA because it can effectively reduce postoperative blood loss and the incidence of wound hematoma. PMID- 27411266 TI - [CLINICAL OBSERVATION OF ONE-STAGE ARTHROSCOPIC RECONSTRUCTION AND STRICT IMMOBILIZATION FOR TREATMENT OF KNEE DISLOCATION]. AB - OBJECTIVE: To investigate the effectiveness of one-stage arthroscopic reconstruction and strict immobilization for 6 weeks for treatment of knee dislocation. METHODS: Between August 2010 and May 2013, 22 cases (22 knees) of knee dislocation were treated with one-stage reconstruction and strict immobilization for 6 weeks. There were 15 males and 7 females, aged 21-54 years (mean, 31.5 years). The left knee and right knee were involved in 8 cases and 14 cases respectively. The disease causes were traffic accident in 12 cases, falling from height in 6 cases, and sports injury in 4 cases. The time between injury and operation was less than 2 weeks in 6 cases, 2-3 weeks in 10 cases, and more than 3 weeks in 6 cases. The results of anterior drawer test, posterior drawer test, and Lachman test were positive in all patients. The posterior displacement of the tibia was more than 10 mm. The results of valgus stress test and varus stress test were positive in 13 cases and 11 cases respectively. The preoperative knee range of motion was (58.2 +/- 28.4) degrees , Lysholm score was 39.7 +/- 4.6. All patients had anterior cruciate ligament rupture and posterior cruciate ligament rupture; combined injuries included medial collateral ligament rupture in 11 cases, lateral collateral ligament rupture in 9 cases, both medial and lateral collateral ligament rupture in 2 cases, femoral condylar avulsion fracture in 2 cases, and meniscus injury in 7 cases. No nerve or blood vessel injury was observed. RESULTS: All cases obtained primary healing of incision without infection. All the patients were followed up 12-48 months (mean, 27.8 months). At 12 months after operation, the results of the anterior drawer test, posterior drawer test, Lachman test, valgus stress test, and varus stress test were all negative; the knee range of motion increased was significantly to (121.3 +/- 7.9) degrees (t = 30.061, P = 0.000); Lysholm score was 87.2 +/- 6.1, showing significant difference when compared with preoperative score (t = 24.642, P = 0.000). CONCLUSION: A combination oathogopi osta ge reconstruction and strict immobilization for treatment of knee dislocation is a safe and effective method, good stability and joint function can be achieved. PMID- 27411268 TI - [EFFECTS OF TOURNIQUET USE ON PERIOPERATIVE OUTCOME IN TOTAL KNEE ARTHROPLASTY]. AB - OBJECTIVE: To clarify the effects of tourniquet use on pain, early rehabilitation, blood loss, incidence rate of thrombosis in primary total knee arthroplasty (TKA) through a randomized controlled trial. METHODS: Between Janurary 2014 and August 2015, 168 patients with knee osteoarthritis undergoing primary TKA were randomly allocated to tourniquet group (n = 84) or non tourniquet group (n = 82). There was no significant difference in gender, age, body mass index, affected side, osteoarthritis grading, disease duration, preoperative range of motion (ROM), visual analogue scale (VAS), Hospital for Special Surgery (HSS) score, and hemoglobin (Hb) between 2 groups (P > 0.05). The operation time, hospitalization time, 90 degrees knee flexion time, straight leg lifting time, and ambulation time were compared between 2 groups. Intraoperative blood loss, Hb decrease, postoperative VAS score, HSS score, ROM, and postoperative complications were recorded and compared. RESULTS: There was no significant difference in operation time (t = -1.353, P = 0.178). The patients were followed up 3-20 months (mean, 12 months) in tourniquet group, and 3-22 months (mean, 13 months) in non-tourniquet group. No significant difference was found in Hb decrease (t = -1.855, P = 0.066) and transfusion rate (23.81% of tourniquest group vs. 25.61% of non-tourniquest group) (chi2 = 0.072, P = 0.788) between 2 groups. Significant difference was found in the incidence rate of thrombosis between tourniquet and non-tourniquet groups (10.71% vs. 2.44%) (chi2 = 4.592, P = 0.032), and the intraoperative blood loss of tourniquet group was significantly less than that of non-tourniquet group (t = -16.066, P = 0.000). The 90 degrees knee flexion time, straight leg lifting time, ambulation time, and hospitalization time of tourniquet group were significantly later than those of non-tourniquet group (P < 0.05). The tourniquet group had significantly higher VAS score at 3, 5, 7, and 14 days after operation (P < 0.05) and lower HSS score at 28 days after operation (t = -4.192, P = 0.000) than non-tourniquet group, but there was no significant difference in the ROM between 2 groups (t = 0.676, P = 0.500). CONCLUSION: The use of a tourniquet during TKA will increase knee pain and thrombotic events, but can not decrease total blood loss and transfusion rate. A tourniquet use during TKA is unfavorable for early rehabilitation progress. PMID- 27411269 TI - [PROMOTION EFFECT OF FTY-720P ON TREATMENT OF BONE DEFECT WITH ALLOGRAFT BONE BY SUPPRESSING OSTEOCLAST FORMATION AND FUNCTION]. AB - OBJECTIVE: To explore whether FTY-720P could enhance the effect of allograft bone for bone defect repair by suppressing osteoclast formation and function. METHODS: Animal experiment: Forty-eight New Zealand white rabbits were selected to establish the tibia defect model (1.5 cm in length) and were divided into 4 groups (n = 12). Defect was not repaired in group A, defect was repaired with allograft bone in group B, with autogenous fibula in group C, and with allograft bone and FTY-720P in group D. Lane-Sandhu scoring system and bone density examination were used to evaluate the effect at 2, 4, 8, and 12 weeks after operation. Cell experiment: Bone marrow-derived mononuclear phagocytes (BMMs) were harvested from 1-month-old Sprague Dawley rats and induced into osteoclasts with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL), then were identified with tartrate resistant acid phosphatas (TRAP). According to different concentrations of FTY 720P before induction, experiment was divided into 0, 500, 600, 700, 800, 900, 1,000, and 1,500 ng/mL groups. The effect of FTY-720P was studied by counting the number of osteoclasts and the number of bone resorption lacunae made by osteoclasts. RESULTS: Animal experiment: Lane-Sandhu score showed no significant difference between groups at 2 weeks after operation (P > 0.05), but the score was significantly better in groups C and D than groups A and B, and in group B than group A (P < 0.05). The bone density of group C was significantly greater than that of groups A, B, and D at 2 weeks after operation (P < 0.05), but no significant difference was found among groups A, B, and D (P > 0.05); the bone density of groups B, C, and D was significantly greater than that of group A at 4, 8, and 12 weeks (P < 0.05), but no significant difference was shown among groups B, C, and D (P > 0.05). Cell experiment: BMMs could be induced into osteoclasts by the addition of M-CSF and RANKL, which could be proved by counting the number of the nuclear and TRAP staining. The osteoclasts were significantly more in 0, 500, 600, 700, 800, 900 ng/mL groups than 1 000 and 1 500 ng/mL groups (P < 0.05), in 0, 500, 600, and 700 ng/mL groups than 800 and 900 ng/mL groups (P < 0.05), in 0, 500, 600 ng/mL groups than 700 ng/mL group (P < 0.05); and there was no significant difference between the other groups (P > 0.05). The number of bone resorption lacunae in 0, 500, 600, and 700 ng/mL groups was significantly higher than that in 800, 900, 1,000, and 1,500 ng/mL groups (P < 0.05), and it was significantly higher in 0, 500 and 600 ng/mL groups than 700 ng/mL group (P < 0.05), but difference was not significant between the other groups (P > 0.05). CONCLUSION: FTY-720P combined with allograft bone for bone defect repair can have the same effect to autogenous bone by means of inhibiting osteoclast formation and function, which reduces bone loss. PMID- 27411270 TI - [MODEL ESTABLISHING OF PARTIAL-THICKNESS ARTICULAR CARTILAGE INJURY AND RELATIONSHIPS BETWEEN ACTIVATION OF CELLS AND EXPRESSION OF INTEGRIN beta1IN A RAT MODEL]. AB - OBJECTIVE: To investigate the relationships between the expression of integrin beta1and activated cells in a partial-thickness articular cartilage injury model of adult rats. METHODS: Forty-five male Sprague Dawley rats (aged 10 weeks and weighing 300-400 g) were randomly divided into operated group (n = 15), sham operated group (n = 15), and control group (n = 15). Partial-thickness articular cartilage injury model was made by scarification in operated group, direct suture after opening of the knee joint was performed in sham-operated group, and no operation was done in control group. Five rats were sacrificed at 1, 7, and 14 days after operation respectively for macroscopic evaluation, HE staining, Safranin O staining, CD105, BrdU, CD105/integrin beta1immunofluorescence and double labeling staining. The histological score of HE staining, gray value of Safranin O staining and CD105-positive cells count were compared among groups at each time point. RESULTS: Macroscopic evaluation showed chondromalacia and cartilage fibrosis around the linear injury with aggravating tendency with time in operated group, but no chondromalacia and cartilage fibrosis in sham-operated and control groups. HE staining demonstrated a number of activated cells accumulating around the linear injury with nonuniform distribution in operated group, and uniform size and distribution in sham-operated and control groups. The histological scores at each time point in operated group were significantly higher than those in sham-operated group and control group (P < 0.05), but no significant difference was found between different time points in 3 groups (P > 0.05). Safranin O staining was nonuniform with hypochromasia around linear injury in operated group, but the staining was uniform in sham-operated group and control group. Gray value of Safranin O staining had no significant difference among groups and among different time points in the same group (P > 0.05). BrdU positive and CD105-positive cells distributed unevenly around the linear injury in operated group, uniform distribution was observed in sham-operated group and control group. CD105-positive cells count in operated group was significantly higher than those in sham-operated group and control group at each time point (P < 0.05); CD105-positive cells increased significantly with time in operated group (P < 0.05). CD105/integrin beta1-positive cells were observed around the linear injury in operated group, but was not observed in sham-operated group and control group. CONCLUSION: The partial-thickness articular cartilage injury model is successfully established in rats, and cartilage injury could not be repaired completely in the model. The activated cells aggregation around the linear injury can be observed, but there is no obvious relationships between activated cells and cartilage matrix. These activated cells are in proliferation and could express both CD105 and integrin beta1. PMID- 27411271 TI - [APPLICATION OF THE DOUBLE SKIN PADDLE ARTERIALIZED VENOUS FLAPS FOR RECONSTRUCTING SOFT TISSUE DEFECTS OF MIDDLE AND PROXIMAL PARTS OF DOUBLE FIGURES]. AB - OBJECTIVE: To investigate the application of the double skin paddle arterialized venous flaps for reconstruction of soft tissue defects in the middle and proximal parts of double fingers. METHODS: Between September 2011 and December 2014, 6 cases (12 fingers) of soft tissue defects in the middle and proximal parts of double fingers underwent reconstructive surgery with the double skin paddle arterialized venous flaps. There were 5 males and 1 female with an average age of 33.8 years (range, 19-52 years). The causes included cut injury in 4 cases and crush injury in 2 cases. Five index fingers, 3 middle fingers, 2 ring fingers, and 2 little fingers were involved. All defects located at proximal and middle fingers and defect did not exceed the distal interphalangeal joint. The defect area ranged from 2.5 cm x 2.5 cm to 5.5 cmx4.0 cm. All cases had bone or tendon exposure, and 2 cases had phalangeal fracture. The disease duration was 1.5-7 hours (mean, 3.5 hours). The flap size was 8 cm x 3 cm-14 cm x 5 cm. The donor site was directly sutured (<= 3.0 cm in width) or was repaired with skin graft (> 3.0 cm in width). RESULTS: The operation time was 2.5-5.0 hours (mean, 4.0 hours). All flaps survived completely. Tensive blisters occurred in 4 cases and were improved at 1 week after removal of suture around pedicle. Partial distal flap necrosis was noted in 1 case, healing was obtained after secondary debridement; other wounds healed in one stage. The patients were followed up 6-18 months (mean, 13 months). The flap had good texture, elasticity, and appearance. According to the hand function evaluation criteria issued by the Chinese Hand Society, the results were excellent in 3 cases, good in 2 cases, and fair in 1 case at last follow-up. The two-point discrimination of the flap was 8-10 mm (mean, 9 mm). CONCLUSION: The double skin paddle arterialized venous flaps have the advantages of simple technique and definite effectiveness for reconstruction of soft tissue defects in the middle and proximal part of double fingers. PMID- 27411272 TI - [CLINICAL APPLICATION OF LATERAL ARM LOBULATED FLAPS TO REPAIR MULTIPLE SOFT TISSUE DEFECT OF HAND]. AB - OBJECTIVE: To explore the effectiveness and operation of repairing multiple soft tissue defects in hands with lateral arm lobulated flaps. METHODS: Between October 2013 and September 2015, 13 cases of multiple soft tissue defects in the hand with tendon or bone exposure were treated with lateral arm lobulated flaps. All patients were males with average age of 28 years (range, 23-45 years). Defects were caused by penetrating injury in 7 cases, traffic accident injury in 3 cases, and hot-crush injury in 3 cases. Six patients had skin defect of the left 2 fingers after opening finger amputation, and 7 patients had skin defect of the palm and the back after hand injury. The size of skin defects ranged from 6 cm x 5 cm to 9 cm x 6 cm. All patients underwent emergency debridement and two stage repair; the duration from injury to operation was 5-9 days (mean, 7 days). The size of flap was 6 cm x 5 cm-9 cm x 6 cm. RESULTS: All flaps survived completely, with no vascular crisis. Primary healing was obtained at donor and recipient sites, and the grafted skin survived. All cases were followed up 3-24 months (mean, 12 months). The appearance and texture of the flaps were similar to those of adjacent skin. Bulky flap was observed in 4 cases, and second stage operation was performed to make the flap thinner at 3 months after operation. The sensation of flap reached S3-S4. CONCLUSION: The lateral arm lobulated flap based on the radial collateral artery has constant vascular anatomy, easy-to-harvest, and large rotation angle. It is an effective procedure to repair small and medium size skin defects of the hand with satisfied texture and sensory recovery. PMID- 27411273 TI - [COMPARISON OF REPAIR EFFECT BETWEEN CHIMERIC ANTEROLATERAL THIGH FLAP AND SERIES WOUND FLAPS FOR DEFECT AFTER RESECTION OF ORAL AND MAXILLOFACIAL CANCER]. AB - OBJECTIVE: To compare the effectiveness of complex defects repair between using chimeric anterolateral thigh flap and series-wound flaps after resection of oral and maxillofacial cancer. METHODS: After resection of oral and maxillofacial cancer, defect was repaired with chimeric anterolateral thigh flap in 39 patients between January 2011 and July 2014 (chimeric anterolateral thigh flap group); and defect was repaired with series-wound flaps in 35 patients between January 2009 and December 2010 (series-wound flaps group). There was no significant difference in gender, age, duration of disease, tumor type, tumor staging, defect location, and defect area between 2 groups (P > 0.05). The operation time, flap harvesting and microvascular anastomosis time, stomach tube extraction time, and oral feeding time were recorded and compared between 2 groups, and postoperative complications were observed; the effectiveness was evaluated according to clinical efficacy evaluation table of bone and soft tissue defects reconstruction surgery in oral and maxillofacial region. RESULTS: Vascular crisis occurred in 2 cases of chimeric anterolateral thigh flap group, and 4 cases of series-wound flaps group. Partial necrosis appeared at distal end of a series-wound flaps, and oral fistula and infection developed in 3 series-wound flaps. The other flaps and the grafted skin at donor site survived; wounds at recipient site healed by first intention. The operation time, stomach tube extraction time, and oral feeding time of chimeric anterolateral thigh flap group were significantly shorter than those of series-wound flaps group (P < 0.05), while the flap harvesting and microvascular anastomosis time was significantly longer than that of series-wound flaps group (P < 0.05). The patients were followed up 1-5 years (mean, 2.5 years). At 3 months after operation, the appearance, patients' satisfaction, working conditions, oral closure function, chew, language performance, and swallowing scores of the chimeric anterolateral thigh-flap group were significantly better than those of the series-wound flaps group (P < 0.05), while there was no significant difference in diet, mouth opening degree, oral cavity holding water test, and occlusion scores between the 2 groups (P > 0.05). CONCLUSION: Using chimeric anterolateral thigh flap for defect repair after resection of oral and maxillofacial cancer can significantly shorten the operation time, accelerate postoperative rehabilitation, and help the functional recovery of oral closure, chewing, language performance, swallowing function when compared with the series-wound flaps. PMID- 27411274 TI - [CLINICAL STUDY ON ZYGOMATIC SPINDLE-SHAPED OSTEOTOMY AND INTERNAL PUSH OF TITANIUM SCREW ANCHOR IN TREATMENT OF PROMINENT MALAR]. AB - OBJECTIVE: To explore the effectiveness of the zygomatic spindle-shaped osteotomy and internal push of titanium screw anchor for prominent malar. METHODS: Between July 2011 and January 2015, 58 patients with prominent malar underwent zygomatic spindle-shaped osteotomy and internal push of titanium screw anchor. There were 3 males and 55 females, aged 18-33 years (mean, 23 years). They had congenital bilateral prominent malar. Preoperative anteroposterior, lateral, supine position, 45" oblique photographs of the face were taken, three-dimensional CT reconstruction of face was performed. Simple prominent malar was observed in 30 cases, and prominent malar and zygomatic arch in 28 cases; zygomatic bone and zygomatic arch were symmetrical in 51 cases, and asymmetrical in 7 cases. RESULTS: All patients obtained stage I incision healing after operation, without infection or hematoma. Numbness of the upper lip occurred in 2 cases, limitation of mouth opening in 1 case, and nasolabial fold deepening in 1 case, which recovered spontaneously after 3 months. Fifty-eight cases were followed up 6-12 months (mean, 10 months). Zygomatic narrow spacing was 10.6-13.9 mm (mean, 11.2 mm). No ptosis of facial soft tissue, zygomatic step, facial nerve injury, raising eyebrow, dysfunction of eyes closure, or temporomandibular joint disorder syndrome occurred. Good bone healing was obtained, zygomatic facial sensation had no obvious abnormality, all patients were satisfied with the improvement of appearance. CONCLUSION: Zygomatic spindle-shaped osteotomy and internal push titanium screw anchor can effectively reduce the cheekbones, and maintain the natural curve of zygomatic body and zygomatic arch. Because of simple operation, less complications, and excellent results, it is an ideal plasty. PMID- 27411275 TI - [CLINICAL OBSERVATION OF MODERATE TO SEVERE BLEPHAROPTOSIS CORRECTION WITH ARC SHAPED FRONTALIS APONEUROSIS FLAP]. AB - OBJECTIVE: To evaluate the effectiveness of an arc-shaped frontalis aponeurosis flap for the treatment of moderate to severe blepharoptosis. METHODS: Between January 2011 and December 2014, 80 cases (140 eyes) of moderate to severe blepharoptosis were treated, including 31 males and 49 females with a median age of 16 years (range, 6-45 years). One eye was involved in 20 cases and both eyes in 60 cases. Upper eyelid ptosis degree ranged from 3 to 6 mm (average, 5 mm) when looking at the front horizontally. Fifty-one patients had underwent plastic surgery, and the first operation was performed in others. The arc-shaped frontalis aponeurosis flap was created by incision of upper and middle edge of the eyebrow, then it was retracted to the upper eyelid aponeurosis and was fixed in a slight over-correction position. RESULTS: The operation was completed smoothly. The intraoperative blood loss was 5-10 mL (mean, 7 mL). Mild swelling of incision was observed after operation, and disappeared at 3-5 days after operation. Primary healing of incision was obtained, with no complications of infection and flap necrosis. The follow-up duration was 1-3 years (mean, 1.5 years). Seventy-nine cases could close upper eyelid completely and the function of upper eyelid was satisfactory within 3 months. One patient could not close upper eyelid completely after 6 months, and mild keratitis occurred, which was cured by anchyloblepharon. CONCLUSION: The arc-shaped frontalis aponeurosis flap can be regarded as a minimally invasive procedure for the treatment of cogenital moderate to severe blepharoptosis, it was safe, reliable, and easy-to-grasp. PMID- 27411276 TI - [HEALING MODEL RESEARCH OF ROTATOR CUFF INJURY IN CANINE]. AB - OBJECTIVE: To compare the difference of rotator cuff healing between different types of injury andbetween different repair methods, and to explore the animal model to accurately simulate the restorative process afterrepair of rotator cuff injury. METHODS: Twelve adult male beagle dogs (weighing, 10-15 kg) were divided into 3 groups (n = 4) according to different processing methods: acute rotator cuff injury+Mason-Allen suture repair (group A), huge rotator cuff injury+Mason Allen suture repair (group B), and huge rotator cuff injury+Mason-Allen combined with autogenous semitendinosus expansion suture repair (group C). The external fixation was used for immobilization after repair. After operation, the general situation of the animals was observed, and the infraspinatus tendon was harvested for gross observation at 6 weeks after operation. The biomechanical test of limit load and histological observation of tendon fibers were carried out. RESULTS: All the animals survived to the end of the experiment. All incisions healed well and no infection occurred. Gross observation showed more scar tissues at the end of infraspinatus muscle tendon than normal tendon in group A; no obvious tendon tissue was observed at the end of infraspinatus muscle tendon in group B; the infraspinatus muscle tendon was covered with some white scar tissue, but the tendon and the general direction could be observed in group C. The limit load of groups A, B, and C were (223.75 +/- 24.28), (159.25 +/- 34.87), and (233.25 +/- 14.24) N respectively, group B was significantly lower than groups A and C (P < 0.05), and no significant differnce was found between group A and group C (P > 0.05). Histological observation showed normal arrangement of tendon fibers in group A; tendon fibers arranged disorderly in group B and tendon cells were significantly less than those of group A; tendon fibers arranged in neat in group C and tendon cells were more than those of group B. CONCLUSION: Canine autologous semitendinosus expansion repair of massive rotator cuff injury immobilization model can better simulate the clinical rotator cuff injury healing process, so it can be used as an ideal animal model for related research. PMID- 27411277 TI - [EFFECT OF TIME-RELATED ADMINISTRATION OF METHOTREXATE ON SPINAL CORD INJURY INDUCED NEURAL CELL APOPTOSIS IN RATS]. AB - OBJECTIVE: To evaluate the effect of time-related administration of methotrexate (MTX) on neural cell apoptosis in rats after spinal cord injury (SCI) so as to investigate its potential neuroprotective mechanism and appropriate administration time. METHODS: A total of 120 male Sprague Dawley rats, 247-286 g in weight, were randomly divided into 4 groups (n=30): sham group (group A), control group (group B), MTX treating group (group C), and MTX prophylaxis group (group D). The SCI model was established in the rats of groups B, C, and D by improved Allen method, and just laminectomy was performed in group A. MTX (0.5 mg/kg) was administered with tail vein injection at 1, 6, 12, 18, and 24 hours after injury in group C, and at 30 minutes before injury and at 6, 12, 18, and 24 hours after injury in group D; the equivalence saline was injected at 1, 6, 12, 18, and 24 hours after injury in groups A and B. Basso-Beattie- Bresnahan (BBB) score was used to evaluate the neural function at 1, 3, 7, 14, and 21 days after injury, HE staining to observe histological changes, immunohistochemical staining and TUNEL method to measure the expression of Caspase-3 and neural cells apoptosis, respectively. RESULTS: Ten rats died during the experiment in groups B, C, and D; 25 rats in each group were included into the experiments at last. BBB score of group A was significantly higher than that of groups B, C, and D at all time points after injury (P<0.05). BBB score of groups C and D were significantly higher than that of group B at 3, 7, 14, and 21 days (P < 0.05), and BBB score of group D was significantly higher than that of group C at 3, 7, and 14 days (P < 0.05). The histological observation showed normal structure of spinal cord at all time points after injury in group A. While the degree of SCI in group D was lighter than that in groups B and C, and group C was lighter than group B. At 14 days after injury, the degree of SCI in groups B, C, and D tend to keep the same. The number of Caspase-3 and TUNEL positive cells of groups B, C, and D was significantly more than that of group A at all time points after injury (P < 0.05), group B was significantly more than groups C and D (P < 0.05). The number of Caspase-3 positive cells of group C was significantly more than that of group D at 3, 7, and 14 days (P < 0.05). While the number of TUNEL positive cells of group C was significantly more than that of group D at 3 and 7 days (P < 0.05). And the number of Caspase-3 positive cells and TUNEL positive cells was positively correlated in groups B, C, and D (P < 0.05) at 1, 3, 7, 14, and 21 days after injury. CONCLUSION: Low-dose MTX may effectively reduce the degree of the secondary injury of spinal cord by reducing the nerve cell apoptosis. Better effect can be obtained when MTX is used as prevent method than as a way of treatment. PMID- 27411278 TI - [COMPARISON OF TUMOR NECROSIS FACTOR alpha INDUCED APOPTOSIS BETWEEN SYNOVIUM DERIVED MESENCHYMAL STEM CELLS AND BONE MARROW MESENCHYMAL STEM CELLS]. AB - OBJECTIVE: To investigate the anti-apoptotic ability of synovium-derived mesenchymal stem cells (SMSCs) by comparing the apoptosis induced by tumor necrosis factor alpha (TNF-alpha) between SMSCs and bone marrow mesenchymal stem cells (BMSCs). METHODS: SMSCs and BMSCs were isolated with tissue adhering and density gradient centrifugation respectively, and cells at passages 3-5 were used in further experiments. After immunophenotype identification and differentiation induction, cells were divided into 4 groups. In the experimental groups, apoptosis of SMSCs and BMSCs were induced by 20 ng/mL TNF-alpha and 10 ug/mL cycloheximide, and cells were cultured in normal culture medium in the control groups. Cellular morphology were observed by inverted phase contrast microscope. After apoptosis induction for 24 hours, cell viability was determined by cell counting kit 8 assay and apoptotic index was detected by flow cytometer. Moreover, the level of Cleaved Caspase-8, 3 were determined by Western blot. RESULTS: Both SMSCs and BMSCs accorded with the definition criteria of MSCs according to results of immunophenotype identification and differentiation induction. After apoptosis induction, cells became shrinking and partially floated and cellular morphologies became worse than those in the control groups. After apoptosis induction for 24 hours, cell viabilities of SMSCs and BMSCs in the control groups were both 100%, and no apoptotic cells were observed. However, cell viabilities of SMSCs and BMSCs in the experimental groups were 60.13% +/- 8.63% and 46.55% +/- 10.54% respectively, which were both significantly lower than those in the control groups (P < 0.05), and cell viability in the SMSCs experimental group was significantly higher than that in the BMSCs experimental group (t = 3.152, P = 0.006). The apoptotic index was 36.54% +/- 8.63% in the SMSCs experimental group and was 53.77% +/- 11.52% in the BMSCs experimental group, both were significantly higher than the control groups (1.12% +/- 0.24% and 1.35% +/- 0.31%) (P < 0.05). What's more, it was significantly lower in SMSCs experimental group than that in BMSCs experimental group (t = 3.785, P = 0.001). Moreover, no expression of Cleaved Caspase-8, 3 was detected in the control groups. But the levels of Cleaved Caspase-8, 3 were significantly enhanced in the experimental groups and they were lower in SMSCs than in BMSCs (t = 13.870, P = 0.000; t = 7.309, P = 0.000). CONCLUSION: TNF-alpha induced apoptosis is lower in SMSCs than in BMSCs, which means that SMSCs may have stronger anti-apoptosis ability than BMSCs. PMID- 27411279 TI - [EFFECT OF Akt1 GENE TRANSFECTION ON HYPOXIA TOLERANCE OF BONE MARROW MESENCHYMAL STEM CELLS]. AB - OBJECTIVE: To investigate whether Akt1 gene transfection mediated by recombinant lentivirus (LVs) in the bone marrow mesenchymal stem cells (BMSCs) could enhance the ability of hypoxia tolerance so as to provide a theoretical basis for improving the effectiveness of stem cells transplantation. METHODS: LVs was used as transfection vector, enhanced green fluorescent protein (EGFP) was used as markers to construct the pLVX-EGFP-3FLAG virus vector carrying the Akt1 gene. The 3rd generation BMSCs from 3-5 weeks old Sprague Dawley rats were transfected with pLVX-EGFP virus solution as group B and with pLVX-EGFP-3PLAG virus solution as group C; and untransfected BMSCs served as control group (group A). At 2-3 days after transfection, the expression of green fluorescent was observed by fluorescence microscope; and at 48 hours after transfection, Western blot method was used to detect the expression of Akt1 protein in groups B and C. BMSCs of groups B and C were given hypoxia intervention with 94% N2, 1% O2, and 5% CO2 for 0, 3, 6, 9, and 12 hours (group B1 and group C1). The flow cytometry was used to analyze the cell apoptosis rate and cell death rate, and the MTT method to analyze the cell proliferation, and Western blot to detect the expression of apoptosis related gene Caspase-3. RESULTS: After transfection, obvious green fluorescence was observed in BMSCs under fluorescence microscopy in groups B and C, the transfection efficiency was about 60%. Akt1 expression of group C was significantly higher than that of group B (t = 17.525, P = 0.013). The apoptosis rate and cell death rate of group B1 increased gradually with time, and difference was significant (P < 0.05). In group C1, the apoptosis rate and cell death rate decreased temporarily at 3 hours after hypoxia intervention, then increased gradually, and difference was significant (P < 0.05). The apoptosis rate and cell death rate of group C1 were significantly lower than those of group B1 at each time point (P < 0.05) except at 0 hour. MTT assay showed tat absorbance (A) values of groups B and C were significantly higher than those of groups B1 and C1 at each time point (P < 0.05); the A value of group B was significantly lower than that of group C at each time point (P < 0.05). The A value of group B1 was significantly lower than that of group Cl at 6, 9, and 12 hours after hypoxia intervention (P < 0.05). Western blot results showed that the Caspase-3 expression of group C1 significantly reduced when compared with group B1 at each time point (P < 0.05). CONCLUSION: Akt1 gene transfection mediated by recombinant LVs could significantly improve hypoxia tolerance of BMSCs by inhibiting the apoptosis, which could provide new ideas for improving the effectiveness of stem cells transplantation. PMID- 27411280 TI - [CO-TRANSPLANTATION OF MOUSE EPIDERMIS AND DERMIS CELLS IN INDUCING HAIR FOLLICLE REGENERATION]. AB - OBJECTIVE: To investigate the co-transplantation of C57-green fluorescent protein (GFP) mouse epidermis and dermis cells subcutaneously to induce the hair follicle regeneration. METHODS: C57-GFP mouse epidermis and dermis were harvested for isolation the mouse epidermis and dermis cells. The morphology of epidermis and dermis mixed cells at ratio of 1:1 of adult mouse, dermis cells of adult mouse, cultured 3rd generation dermis cells were observed by fluorescence microscope. Immunocytochemistry staining was used to detect hair follicle stem cells markers in cultured 3rd generation dermis cells from new born C57-GFP mouse. And then the epidermis and dermis mixed cells of adult mouse (group A), dermis cells of adult mouse (group B), cultured 3rd generation dermis cells of new born mouse (group C), and saline (group D) were transplanted subcutaneously into Balb/c nude mice. The skin surface of nude mice were observed at 4, 5, 6 weeks of transplantation and hair follicle formation were detected at 6 weeks by immunohistochemistry staining. RESULTS: The isolated C57-GFP mouse epidermis and dermis cells strongly expressed the GFP under the fluorescence microscope. Immunocytochemistry staining for hair follicle stem cells markers in cultured 3rd generation dermis cells showed strong expression of Vimentin and alpha-smooth muscle actin, indicating that the cells were dermal sheath cells; some cells expressed CD133, Versican, and cytokeratin 15. After transplanted for 4-6 weeks, the skin became black at the injection site in group A, indicating new hair follicle formation. However, no color change was observed in groups B, C, and D. Immunohistochemical staining showed that new complete hair follicles structures formed in group A. GFP expression could be only observed in the hair follicle dermal sheath and outer root sheath in group B, and it could also be observed in the hair follicle dermal sheath, outer root sheath, dermal papilla cells, and sweat gland in group C. The expression of GFP was negative in group D. CONCLUSION: Co-transplantation of mouse epidermis and dermis cells can induce the hair follicle regeneration by means of interaction of each other. And transplantation of isolated dermis cells or cultured dermis cells individually only partly involved in the hair follicles formation. PMID- 27411281 TI - [PREPARATION AND BIOCOMPATIBILITY EVALUATION OF A FUNCTIONAL SELF-ASSEMBLING PEPTIDE NANOFIBER HYDROGEL DESIGNED WITH LINKING THE SHORT FUNCTIONAL MOTIF OF BONE MORPHOGENETIC PROTEIN 7]. AB - OBJECTIVE: To prepare of a novel functional self-assembling peptide nanofiber hydrogel scaffold RADKPS designed with linking the short functional motif of bone morphogenetic protein 7 (BMP-7) and to evaluate its biocompatibiity so as to provide the experimental basis for in viva studies on regeneration of degenerated nucleus pulposus tissue. METHODS: A functional self assembling peptide RADA-KPSS was designed by linking the short functional motif of BMP-7 to the self assembling peptide RADA16-I. And the novel functional self assembling peptide RADKPS was finally prepared by isometric mixing RADA16-I with RADA-KPSS. The structure characteristic of the functional self-assembling peptide nanofiber hydrogel scaffold RADKPS was evaluated by general observation and atomic force microscopy. Bone marrow mesenchymal stem cells (BMSCs) were isolated from 3-month old New Zealand white rabbits and cultured. After the 3rd generation BMSCs were seeded on the peptide nanofiber hydrogel scaffold RADKPS for 7 days, the cellular compatibility of RADKPS was evaluated through scanning electron microscopy assay, cellular fluorescein diacetate/propidium iodide staining, and MTT assay. 1%RADKPS was injected into isolated intervertebral disc organs from 6-month-old New Zealand white rabbits, then the organs were cultured and the cellular activity of the intervertebral disc organs was observed. The blood compatibility of RADKPS was evaluated with hemolytic assay. After RADKPS was implanted into subcutaneous part of Kunming mice (aged 6-8 weeks) for 28 days, general observation and HE staining were carried out to evaluate the tissue compatibility. RESULTS: The functional self-assembling peptide solution RADKPS presented a homogeneous transparent hydrogel-like. Atomic force microscopy revealed that the RADKPS could self-assemble into three-dimensional nanofiber hydrogel scaffolds; the fibre diameter was (25.68 +/- 4.62) nm, and the fibre length was (512.42 +/- 32.22) nm. After BMSCs cultured on RADKPS for 7 days, scanning electron microscopy showed that BMSCs adhered to the scaffolds. And cell viability was maintained over 90%. MTT assay revealed that RADKPS of 0.1%, 0.05%, and 0.025% could increase the proliferation of BMSCs. The result of hemolytic assay revealed that the hemolysis rates of the RADKPS solutions with different concentrations were less than 5%, indicating that it met the requirement of hemolytic assay standard for medical biomaterials. After subcutaneous implantation, no vesicle, erythema, and eschar formation around injection site were observed. Meanwhile, HE staining showed inflammatory cells infiltration (lymphocytes), substitution of hydrogel scaffold by fibrous tissue, and good tissue compatibility. CONCLUSION: The novel functional self-assembling peptide nanofiber hydrogel scaffold RADKPS has good biocompatibility and biological reliability, which would be suitable for tissue engineering repair and regeneration of nucleus pulposus tissue. PMID- 27411282 TI - [DEVELOPMENT OF HYPOXIA-INDUCIBLE FACTOR 1alpha IN TISSUE ENGINEERED ANGIOGENESIS AND OSTEOGENESIS]. AB - OBJECTIVE: To review the development and applications of hypoxia-inducible factor la (HIF-1alpha) in the strategy of tissue engineered angiogenesis and osteogenesis. METHODS: The literature about HIF-1alpha in tissue engineering technology was reviewed, analyzed, and summarized. RESULTS: HIF-1alpha plays a key role in arigiogenic-osteogenic coupling, and as an upstream regulator, HIF 1alpha can regulate the expressions of its target genes related with angiogenesis and osteogenesis. In addition, HIF-1alpha not only can control and improve the angiogenesis, but also has important significance in proliferation and differentiation of seed cells, especially stem cells, which is the foundation for bone healing. CONCLUSION: With the development of tissue engineering technology, the problems in the applications of HIF-1alpha, such as the effective dose of targeting controlled-release, pro-inflammatory effect, and carcinogenicity, will be explored and solved in the future, so it can be used better in clinical. PMID- 27411283 TI - [RESEARCH PROGRESS OF THREE-DIMENSIONAL PRINTING POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING]. AB - OBJECTIVE: To summarize the research progress of several three-dimensional (3-D) printing scaffold materials in bone tissue engineering. METHODS: The recent domestic and international articles about 3-D printing scaffold materials were reviewed and summarized. RESULTS: Compared with conventional manufacturing methods, 3-D printing has distinctive advantages, such as enhancing the controllability of the structure and increasing the productivity. In addition to the traditional metal and ceramic scaffolds, 3-D printing scaffolds carrying seeding cells and tissue factors as well as scaffolds filling particular drugs for special need have been paid more and more attention. CONCLUSION: The development of 3-D printing porous scaffolds have revealed new perspectives in bone repairing. But it is still at the initial stage, more basic and clinical researches are still needed. PMID- 27411284 TI - [APPLICATION STRATEGY OF ANKLE AND HINDFOOT ARTHRODESIS]. AB - OBJECTIVE: To summarize the progress in the application of ankle and hindfoot arthrodesis. METHODS: The domestic and foreign related literature about the application of ankle and hindfoot arthrodesis was reviewed, summarized, and analyzed. RESULTS: Ankle and hindfoot arthrodesis include the multi-joint fusion and the single joint fusion, and they involve tibiotalar joint, subtalar joint, talonavicular joint, and calcaneocuboid joint. The methods of fixation include screw, plate, intramedullary nail, and external fixation. CONCLUSION: Different terminal illnesses of ankle and hindfoot have different choices in both the fusion location and the method of fixation, appropriate program for therapeutic purposes can also alleviate complication simultaneously. PMID- 27411285 TI - [ADVANCE IN SURGICAL TREATMENT OF PRIMARY SACRUM TUMOR]. AB - OBJECTIVE: To summarize the research progress of surgical treatment for primary sacrum tumor. METHODS: The domestic and foreign related literature about surgical treatment of primary sacrum tumor, and many aspects of its surgical procedures, intraoperative hemostasis, pelvic reconstruction, protection of sacral nerve, complications, and prognosis was summarized and analyzed. RESULTS: The operation is the major therapy for primary sacrum tumor. However, surgical procedures, protection of sacral nerve, and the way of intraoperative hemostasis remain controversial. Meanwhile, the complexity of pelvic reconstruction, the diversity of complications, and prognosis related with many factors bring difficulties and challenges to the surgical treatment. CONCLUSION: It is urgent need to develop an effective unified standard to conduct diagnosis and treatment of primary sacrum tumor. PMID- 27411286 TI - Eye movement desensitization and reprocessing therapy for personality disorders in older adults? AB - Eye Movement Desensitization and Reprocessing (EMDR) is a kind of psychotherapy, which is growing in popularity, particularly for treatment of post-traumatic stress disorder (PTSD). When Shapiro first introduced EMDR in 1989, it was approached as a controversial treatment because of lack of evidence. However, nowadays there is growing evidence for EMDR efficacy in PTSD (Mc Guire et al., 2014) and EMDR is recommended by international and national treatment guidelines for PTSD. Moreover, EMDR is also used for the treatment of other anxiety disorders, such as panic disorders (De Jongh et al., 2002). Furthermore, research continues on effects of EMDR in addiction, somatoform disorders and psychosis. So far, there is no empirical research on the efficacy of EMDR treatment in older adults. PMID- 27411287 TI - Engeletin Alleviates Lipopolysaccharide-Induced Endometritis in Mice by Inhibiting TLR4-mediated NF-kappaB Activation. AB - Engeletin (dihydrokaempferol 3-rhamnoside) is a flavanonol glycoside. It can be found in the skin of white grapes and white wine and is widely distributed in southeast Asia, and the leaves are used in a tea. Here, we explored the impact of engeletin against the inflammatory reaction in a lipopolysaccharide (LPS)-induced endometritis mouse model. Engeletin treatment significantly attenuated uterus damage and decreased myeloperoxidase activity. ELISA and qPCR assays showed that engeletin dose-dependently suppressed the expression of TNF-alpha, IL-1beta, and IL-6. Molecular studies also demonstrated that the levels of iNOS, COX-2, and TLR4, along with their downstream molecules MyD88, IRAK1, TRAF6, and TAK1, were also suppressed by engeletin. In addition, engeletin treatment inhibited NF kappaB signaling-pathway activation. Moreover, immunofluorescence analysis demonstrated that engeletin suppressed NF-kappaB-p65 nuclear translocation. These data indicated the protective action of engeletin against LPS-stimulated endometritis in mice via negative regulation of pro-inflammatory mediators via the TLR4-regulated NF-kappaB pathway. PMID- 27411288 TI - Light-driven electron injection from a biotinylated triarylamine donor to [Ru(diimine)3](2+)-labeled streptavidin. AB - Electron transfer from a biotinylated electron donor to photochemically generated Ru(iii) complexes covalently anchored to streptavidin is demonstrated by means of time-resolved laser spectroscopy. Through site-selective mutagenesis, a single cysteine residue was engineered at four different positions on streptavidin, and a Ru(ii) tris-diimine complex was then bioconjugated to the exposed cysteines. A biotinylated triarylamine electron donor was added to the Ru(ii)-modified streptavidins to afford dyads localized within a streptavidin host. The resulting systems were subjected to electron transfer studies. In some of the explored mutants, the phototriggered electron transfer between triarylamine and Ru(iii) is complete within 10 ns, thus highlighting the potential of such artificial metalloenzymes to perform photoredox catalysis. PMID- 27411290 TI - Rehabilitation as "destination triage": a critical examination of discharge planning. AB - PURPOSE: In this paper we examine how the intersection of various social and political influences shapes discharge planning and rehabilitation practices in ways that may not meet the espoused aims of rehabilitation programs or the preferences of older adults and their families. METHODS: Taking a critical bioethics perspective, we used microethnographic case study methods to examine discharge-planning processes in a well-established older adult inpatient rehabilitation setting in Canada. The data included observations of discharge planning family conferences and semi-structured interviews conducted with older adults facing discharge, their family members and rehabilitation professionals involved in discharge planning. RESULTS: From the time of admission, a contextual push to focus on discharge superseded program aims of providing interventions to increase older adults' functional capabilities. Professionals' primary commitment to safety limited consideration of discharge options and resulted in costly and potentially unnecessary recommendations for 24-hour care. The resulting "rehabilitation" stay was more akin to an extended process of "destination triage" biased towards the promotion of physical safety than optimizing functioning. CONCLUSIONS: The resulting reduction of rehabilitation into "destination triage" has significant social, financial and occupational implications for older adults and their families, and broader implications for healthcare services and overarching healthcare systems. Implications for Rehabilitation Current trends promoting consideration of discharge planning from the point of admission and prioritizing physical safety are shifting the focus of rehabilitation away from interventions to maximize recovery of function, which are the stated aims of rehabilitation. Such practices furthermore promote assessments to determine prognosis early in the rehabilitation stay when accurate prognosis is difficult, which can lead to overly conservative recommendations for discharge from rehabilitation services, thus further negating the impact of rehabilitation. Further work is required to examine the social, occupational and functional implications of superseding rehabilitation interventions to maximize capabilities with practices that prioritize safety over quality of life for older adults and their family members. PMID- 27411289 TI - TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes. AB - One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-alpha and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes. PMID- 27411291 TI - Novel Triggered Nocturnal Blood Pressure Monitoring for Sleep Apnea Syndrome: Distribution and Reproducibility of Hypoxia-Triggered Nocturnal Blood Pressure Measurements. AB - Obstructive sleep apnea (OSA) causes blood pressure (BP) surges during sleep, which may lead to increased sleep-onset cardiovascular events. The authors recently developed a triggered nocturnal BP monitoring system that initiates BP measurements when oxygen desaturation falls below a variable threshold. The distribution and reproducibility of hypoxia-triggered nocturnal BP parameters compared with those of fixed-interval nocturnal BP parameters for two consecutive nights in 147 OSA patients (mean age 59.4 years, 86.4% men) were evaluated. The mean and distribution (standard deviation [SD]) of the hypoxia-peak systolic BP (SBP) were significantly greater than that of the mean nocturnal SBP (mean+/-SD: 148.8+/-20.5 vs 123.4+/-14.2 mm Hg, P<.001). The repeatability coefficient (expressed as %MV) of hypoxia-peak SBP between night 1 and night 2 was comparable to that of mean nocturnal SBP (43% vs 32%). In conclusion, hypoxia-peak nocturnal BP was much higher than mean nocturnal BP, and it was as reproducible as mean nocturnal BP. PMID- 27411293 TI - Objective Physical Activity Measurement for a Child With Special Health Care Needs. PMID- 27411294 TI - Selective cholesterol adsorption by molecular imprinted polymeric nanospheres and application to GIMS. AB - Molecular imprinted polymers (MIPs) are tailor-made materials with selective recognition to the target. The goals of this study were to prepare cholesterol imprinted polymeric nanospheres (CIPNs) and optimize their adsorption parameters and also to use CIPNs for adsorption of cholesterol (CHO), which is an important physiological biomacromolecule, from gastrointestinal mimicking solution (GIMS). Pre-polymerization complex was prepared using CHO as template and N methacryloylamido-(l)-phenylalanine methyl ester (MAPA). This complex was polymerized with 2-hydroxyethyl methacrylate (HEMA). CHO was removed by MeOH and tetrahydrofuran (THF). Adsorption studies were performed after chacterization studies to interrogate the effects of time, initial concentration, temperature, and ionic strength on CHO adsorption onto CIPNs. Maximum adsorption capacity (714.17mg/g) was higher than that of cholesterol imprinted polymers in literature. Pseudo-second-order kinetics and Langmuir isotherm fitted best with the adsorption onto CIPNs. 86% of adsorbed cholesterol was desorbed with MeOH:HAc (80:20, v/v) and CIPNs were used in adsorption-desorption cycle for 5-times with a decrease as 12.28%. CHO analogues; estron, estradiol, testosterone, and progesterone were used for competitive adsorption. The relative selectivity coefficients of CINPs for cholesterol/estron and cholesterol/testosterone were 3.84 and 10.47 times greater than the one of non-imprinted polymeric nanospheres (NIPNs) in methanol, respectively. PMID- 27411295 TI - Lectins from Parkia biglobosa and Parkia platycephala: A comparative study of structure and biological effects. AB - The relation structure-activity of the Mimosoideae lectins of Parkia platycephala (PPL) and Parkia biglobosa (PBL) was analyzed in this study. PBL was solved by X ray crystallography at a resolution of 2.1A, and the crystal structure belonged to the C2221 space group. Structural organization and binding sites were also characterized. Specifically, PBL monomer consists of three beta-prism domains tandemly arranged with each one presenting a different carbohydrate recognition domain (CRD). PPL showed antinociceptive activity in the mouse model of acetic acid-induced writhes with maximal inhibitory effect by 74% at 1mg/mL. PPL also demonstrated anti-inflammatory effect causing inhibition of leukocyte migration induced by both direct and indirect chemoattractants. These PPL activities were compared to that of PBL described previously. Molecular docking of both PBL and PPL demonstrated some differences in carbohydrate-lectin interaction energy. Comparing structure and biological effects of the two lectins provided new data about their structure and the relation with its biological activities. PMID- 27411296 TI - Determination of the elastic modulus of beta-lactoglobulin amyloid fibrils by measuring the Debye-Waller factor. AB - Although amyloid fibrils are associated with amyloidoses, they are now being considered as novel biomaterials for industrial use due to their structural stability in the matured state. Therefore, the physical characteristics of these materials need to be clarified prior to their industrial application. In the present study, the mechanical properties of amyloid fibrils precursored by beta lactoglobulin were investigated. Previous studies have examined the stiffness or modulus values of these fibrils using atomic force microscopy. However, the modulus values reported, even for amyloid fibrils from the same precursor proteins, range over three orders of magnitude, from a few MPa to GPa, depending on the experimental methods employed under specific loading conditions. We determined the elastic modulus of amyloid fibrils by measuring spontaneous thermal fluctuations in the material, the Debye-Waller factor. This method does not require any contact between the probe and material or any loading. The vibrational modes of a fibril were considered in order to estimate mechanical parameters. The modulus value determined along the fibril axis for single amyloid fibrils was slightly smaller than those reported in the literature. The smaller modulus value suggests the existence of less ordered proto-fibrils in our specimen, which was confirmed by the AFM images. PMID- 27411297 TI - Implication of cerebral circulation time in intracranial stenosis measured by digital subtraction angiography on cerebral blood flow estimation measured by arterial spin labeling. AB - PURPOSE: Arterial spin labeling (ASL) magnetic resonance imaging to assess cerebral blood flow (CBF) is of increasing interest in basic research and in diagnostic applications, since ASL provides similar information to positron emission tomography about perfusion in vascular territories. However, in patients with steno-occlusive arterial disease (SOAD), CBF as measured by ASL might be underestimated due to delayed bolus arrival, and thus increased spin relaxation. We aimed to estimate the extent to which bolus arrival time (BAT) was delayed in patients with SOAD and whether this resulted in underestimation of CBF. METHODS: BAT was measured using digital subtraction angiography (DSA) in ten patients with high-grade stenosis of the middle carotid artery (MCA). Regional CBF was assessed with pseudocontinuous ASL. RESULTS: BATs were nonsignificantly prolonged in the stenotic hemisphere 4.1+/-2.0 s compared with the healthy hemisphere 3.3+/-0.9 s; however, there were substantial individual differences on the stenotic side. CBF in the anterior and posterior MCA territories were significantly reduced on the stenotic hemisphere. Severe stenosis was correlated with longer BAT and lower quantified CBF. CONCLUSION: ASL-based perfusion measurement involves a race between the decay of the spins and the delivery of labeled blood to the region of interest. Special caution is needed when interpreting CBF values quantified in individuals with altered blood flow and delayed circulation times. However, from a clinician's point of view, an accentuation of hypoperfusion (even if caused by underestimation of CBF due to prolonged BATs) might be desirable since it indexes potentially harmful physiologic deficits. PMID- 27411298 TI - Quantum-critical fluctuations in 2D metals: strange metals and superconductivity in antiferromagnets and in cuprates. AB - The anomalous transport and thermodynamic properties in the quantum-critical region, in the cuprates, and in the quasi-two dimensional Fe-based superconductors and heavy-fermion compounds, have the same temperature dependences. This can occur only if, despite their vast microscopic differences, a common statistical mechanical model describes their phase transitions. The antiferromagnetic (AFM)-ic models for the latter two, just as the loop-current model for the cuprates, map to the dissipative XY model. The solution of this model in (2+1)D reveals that the critical fluctuations are determined by topological excitations, vortices and a variety of instantons, and not by renormalized spin-wave theories of the Landau-Ginzburg-Wilson type, adapted by Moriya, Hertz and others for quantum-criticality. The absorptive part of the fluctuations is a separable function of momentum [Formula: see text], measured from the ordering vector, and of the frequency omega and the temperature T which scale as [Formula: see text] at criticality. Direct measurements of the fluctuations by neutron scattering in the quasi-two-dimensional heavy fermion and Fe-based compounds, near their antiferromagnetic quantum critical point, are consistent with this form. Such fluctuations, together with the vertex coupling them to fermions, lead to a marginal fermi-liquid, with the imaginary part of the self-energy [Formula: see text] for all momenta, a resistivity [Formula: see text], a [Formula: see text] contribution to the specific heat, and other singular fermi-liquid properties common to these diverse compounds, as well as to d-wave superconductivity. This is explicitly verified, in the cuprates, by analysis of the pairing and the normal self-energy directly extracted from the recent high resolution angle resolved photoemission measurements. This reveals, in agreement with the theory, that the frequency dependence of the attractive irreducible particle-particle vertex in the d-wave channel is the same as the irreducible particle-hole vertex in the full symmetry of the lattice. PMID- 27411300 TI - Validation of the TONOPORT VI ambulatory blood pressure monitor in adults according to the European Society of Hypertension International Protocol revision 2010. AB - The present study aims to examine the performance of the TONOPORT VI ambulatory blood pressure (BP) monitor in the inflation and deflation measurement methods, according to the European Society of Hypertension International Protocol revision 2010 (ESH-IP 2010). Systolic and diastolic blood pressures (SBP and DBP, respectively) of 33 subjects (23 female, 10 male) were sequentially measured and compared with reference measurements obtained by two observers using a standard mercury sphygmomanometer. The subjects were selected according to the recruitment instructions of the ESH-IP 2010. Three comparative readings were performed per subject. Among the 99 readings in the inflation measurement method were 92/94 (SBP/DBP) with differences ?5, 97/99 ?10 and 98/99 ?15 mm Hg. All of the 33 subjects had at least 2 out of 3 comparative readings with differences ?5 mm Hg and 0/0 of the subjects had no reading ?15 mm Hg. The validation of the deflation measurement method resulted in differences where 93/91 were ?5, 98/98 were ?10, and 99/99 were ?15 mm Hg. Thirty-two of the 33 subjects had at least 2 out of 3 comparative readings ?5 mm Hg and 0/0 of the subjects had no reading ?15 mm Hg. In conclusion, the TONOPORT VI, respectively, in the inflation and deflation measurement methods met all requirements of Part 1 and 2 of the ESH-IP 2010. Based on the study results, the TONOPORT VI can be recommended for BP measurements in adults. PMID- 27411299 TI - Different associations between blood pressure indices and carotid artery damages in a community-based population of China. AB - Different blood pressure (BP) indices had varying associations with carotid intima-media thickness (cIMT) and plaques in clinical practice. However, insufficient evidence has focused on this issue, especially in Chinese population. Herein we examined associations of different BP indices with cIMT and plaques cross-sectionally in a community-based atherosclerosis cohort. We qualitatively measured cIMT and plaques, and also measured central systolic blood pressure and brachial systolic blood pressure (baSBP), from which pulse pressure (PP), and second PP (PP2) were calculated. Logistic multivariate regression was used to assess the associations with BP indices and carotid artery hypertrophy (increased cIMT) and the extent of atherosclerosis (presence of plaques). Each BP index was significantly and independently associated with increased cIMT and plaques except the association of baSBP with plaques. When every two BP indices were put into one model, brachial pressure indices were associated with increased cIMT independently of central pressures, whereas the association between central pressure indices and plaque presence were stronger than those of brachial pressures. In addition, SBP indices were associated with increased cIMT independently of PP indices, whereas PP indices were more strongly related to plaques. In conclusion, central and PP indices might be associated with plaques; however, brachial and SBP indices might be associated with increased cIMT. Nevertheless, whether these BP indices predict increased cIMT and plaque progression warrants further longitudinal and laboratory studies. PMID- 27411301 TI - Dynamics of biomass partitioning, stem gene expression, cell wall biosynthesis, and sucrose accumulation during development of Sorghum bicolor. AB - Biomass accumulated preferentially in leaves of the sweet sorghum Della until floral initiation, then stems until anthesis, followed by panicles until grain maturity, and apical tillers. Sorghum stem RNA-seq transcriptome profiles and composition data were collected for approximately 100 days of development beginning at floral initiation. The analysis identified >200 differentially expressed genes involved in stem growth, cell wall biology, and sucrose accumulation. Genes encoding expansins and xyloglucan endotransglucosylase/hydrolases were differentially expressed in growing stem internodes. Genes encoding enzymes involved in the synthesis of cellulose, lignin, and glucuronoarabinoxylan were expressed at elevated levels in stems until approximately 7 days before anthesis and then down-regulated. CESA genes involved in primary and secondary cell wall synthesis showed different temporal patterns of expression. Following floral initiation, the level of sucrose and other non-structural carbohydrates increased to approximately 50% of the stem's dry weight. Stem sucrose accumulation was inversely correlated with >100-fold down-regulation of SbVIN1, a gene encoding a vacuolar invertase. Accumulation of stem sucrose was also correlated with cessation of leaf and stem growth at anthesis, decreased expression of genes involved in stem cell wall synthesis, and approximately 10-fold lower expression of SbSUS4, a gene encoding sucrose synthase that generates UDP-glucose from sucrose for cell wall biosynthesis. Genes for mixed linkage glucan synthesis (CSLF) and turnover were expressed at high levels in stems throughout development. Overall, the stem transcription profile resource and the genes and regulatory dynamics identified in this study will be useful for engineering sorghum stem composition for improved conversion to biofuels and bio-products. PMID- 27411302 TI - PROX1 and beta-catenin are prognostic markers in pancreatic ductal adenocarcinoma. AB - BACKGROUND: The Wnt/beta-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The role of beta-catenin expression in pancreatic ductal adenocarcinoma is somewhat controversial. Transcription factor PROX1 is a target of Wnt/beta-catenin signaling and it is involved in carcinogenesis through alterations in its expression. The actions can be either oncogenic or tumor suppressive depending on the tissue. The aim of this study was to investigate PROX1 and beta-catenin expression in pancreatic ductal adenocarcinoma (PDAC). METHODS: Expression of PROX1 and beta-catenin were evaluated in 156 patients by immunohistochemistry of tissue microarrays. Associations between tumor marker expression and clinicopathological parameters were assessed by the Fischer's exact-test or the linear-by-linear association test. The Kaplan-Meier method and log-rank test were used for survival analysis. Uni- and multivariate survival analyses were carried out by the Cox regression proportional hazard model. RESULTS: High PROX1 expression was seen in 74 (48 %) tumors, and high beta-catenin expression in 100 (65 %). High beta-catenin expression was associated with lower tumor grade (p = 0.025). High PROX1 and beta-catenin expression associated significantly with lower risk of death from PDAC in multivariate analysis (HR = 0.63; 95 % CI 0.42 0.95, p = 0.026; and HR = 0.54; 95 % CI 0.35-0.82, p = 0.004; respectively). The combined high expression of PROX1 and beta-catenin also predicted lower risk of death from PDAC (HR = 0.46; 95 % CI 0.28-0.76, p = 0.002). CONCLUSION: In conclusion, high PROX1 and beta-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma. PMID- 27411303 TI - Stem cell procedures in arthroscopic surgery. AB - The stem cell as the building block necessary for tissue reparation and homeostasis plays a major role in regenerative medicine. Their unique property of being pluripotent, able to control immune process and even secrete a whole army of anabolic mediators, draws interest. While new arthroscopic procedures and techniques involving stem cells have been established over the last decade with improved outcomes, failures and dissatisfaction still occur. Therefore, there is increasing interest in ways to improve the healing response. MSCs are particularly promising for this task given their regenerative potential. While methods of isolating those cells are no longer poses a challenge, the best way of application is not clear. Several experiments in the realm of basic science and animal models have recently been published, addressing this issue, yet the application in clinical practice has lagged. This review provides an overview addressing the current standing of MSCs in the field of arthroscopic surgery. PMID- 27411306 TI - Identification of phenotype-relevant differentially expressed genes in breast cancer demonstrates enhanced quantile discretization protocol's utility in multi platform microarray data integration. AB - Microarray for transcriptomics experiments often suffer from limited statistical power due to small sample size. Quantile discretization (QD) maps expression values for a sample into a series of equivalently sized 'bins' that represent a discrete numerical range, e.g. [Formula: see text]4 to [Formula: see text]4, which enables normalized data from multiple experiments and/or expression platforms to be combined for re-analysis. We found, however, that informal selection of bin numbers often resulted in loss of the underlying correlation structure in the data through assigning of the same numerical value to genes that are in reality expressed at significantly different levels within a sample. Here we report a procedure for determining an optimal bin number for dataset. Applying this to integrated public breast cancer datasets enabled statistical identification of several differentially expressed tumorigenesis-related genes that were not found when analyzing the individual datasets, and also several cancer biomarkers not previously indicated as having utility in the disease. Notably, differential modulation of translational control and protein synthesis via multiple pathways were found to potentially have central roles in breast cancer development and progression. These findings suggest that our protocol has significant utility in making meaningful novel biomedical discoveries by leveraging the large public expression data repositories. PMID- 27411304 TI - Nosocomial transmission of Clostridium difficile ribotype 027 in a Chinese hospital, 2012-2014, traced by whole genome sequencing. AB - BACKGROUND: The rapid spread of Clostridium difficile NAP1/BI/027 (C. difficile 027) has become one of the leading threats of healthcare-associated infections worldwide. However, C. difficile 027 infections have been rarely reported in Asia, particularly in China. RESULTS: In this study, we identified a rare C. difficile bloodstream infection (BSI) from three isolates of a patient during repeated hospital admission. This finding triggered a retrospective epidemiological study to scan all cases and strains emerged from this ward during the past three years. Using medical personnel interviews, medical record reviews and the genomic epidemiology, two outbreaks in 2012 and 2013-2014 were identified. Through using whole genome sequencing, we succeeded to trace the origin of the BSI strain. Surprisingly, we found the genome sequences were similar to C. difficile 027 strain R20291, indicating the occurrence of a rare C. difficile 027 strain in China. Integrated epidemiological investigation and whole genome sequencing of all strains, we constructed a nosocomial transmission map of these two C. difficile 027 outbreaks and traced the origin of the infection. CONCLUSIONS: By genome sequencing, spatio-temporal analysis and field epidemiology investigation, we can estimate their complex transform network and reveal the possible modes of transmission in this ward. Based on their genetic diversity, we can assume that the toilets, bathroom, and janitor's equipment room may be contaminated area, which may be suggested to improve infection control measures in the following health care. PMID- 27411307 TI - A machine-learning approach for predicting palmitoylation sites from integrated sequence-based features. AB - Palmitoylation is the covalent attachment of lipids to amino acid residues in proteins. As an important form of protein posttranslational modification, it increases the hydrophobicity of proteins, which contributes to the protein transportation, organelle localization, and functions, therefore plays an important role in a variety of cell biological processes. Identification of palmitoylation sites is necessary for understanding protein-protein interaction, protein stability, and activity. Since conventional experimental techniques to determine palmitoylation sites in proteins are both labor intensive and costly, a fast and accurate computational approach to predict palmitoylation sites from protein sequences is in urgent need. In this study, a support vector machine (SVM)-based method was proposed through integrating PSI-BLAST profile, physicochemical properties, [Formula: see text]-mer amino acid compositions (AACs), and [Formula: see text]-mer pseudo AACs into the principal feature vector. A recursive feature selection scheme was subsequently implemented to single out the most discriminative features. Finally, an SVM method was implemented to predict palmitoylation sites in proteins based on the optimal features. The proposed method achieved an accuracy of 99.41% and Matthews Correlation Coefficient of 0.9773 for a benchmark dataset. The result indicates the efficiency and accuracy of our method in prediction of palmitoylation sites based on protein sequences. PMID- 27411305 TI - NOS Expression and NO Function in Glioma and Implications for Patient Therapies. AB - SIGNIFICANCE: Gliomas are central nervous system tumors that primarily occur in the brain and arise from glial cells. Gliomas include the most common malignant brain tumor in adults known as grade IV astrocytoma, or glioblastoma (GBM). GBM is a deadly disease for which the most significant advances in treatment offer an improvement in survival of only ~2 months. CRITICAL ISSUES: To develop novel treatments and improve patient outcomes, we and others have sought to determine the role of molecular signals in gliomas. Recent Advances: One signaling molecule that mediates important biologies in glioma is the free radical nitric oxide (NO). In glioma cells and the tumor microenvironment, NO is produced by three isoforms of nitric oxide synthase (NOS), NOS1, NOS2, and NOS3. NO and NOS affect glioma growth, invasion, angiogenesis, immunosuppression, differentiation state, and therapeutic resistance. FUTURE DIRECTIONS: These multifaceted effects of NO and NOS on gliomas both in vitro and in vivo suggest the potential of modulating the pathway for antiglioma patient therapies. Antioxid. Redox Signal. 26, 986 999. PMID- 27411308 TI - Association of missing paternal demographics on infant birth certificates with perinatal risk factors for childhood obesity. AB - BACKGROUND: The role of fathers in the development of obesity in their offspring remains poorly understood. We evaluated associations of missing paternal demographic information on birth certificates with perinatal risk factors for childhood obesity. METHODS: Data were from the Linked CENTURY Study, a database linking birth certificate and well-child visit data for 200,258 Massachusetts children from 1980-2008. We categorized participants based on the availability of paternal age, education, or race/ethnicity and maternal marital status on the birth certificate: (1) pregnancies missing paternal data; (2) pregnancies involving unmarried women with paternal data; and (3) pregnancies involving married women with paternal data. Using linear and logistic regression, we compared differences in smoking during pregnancy, gestational diabetes, birthweight, breastfeeding initiation, and ever recording a weight for length (WFL) >= the 95th percentile or crossing upwards >=2 WFL percentiles between 0-24 months among the study groups. RESULTS: 11,989 (6.0 %) birth certificates were missing paternal data; 31,323 (15.6 %) mothers were unmarried. In adjusted analyses, missing paternal data was associated with lower birthweight (beta -0.07 kg; 95 % CI: -0.08, -0.05), smoking during pregnancy (AOR 4.40; 95 % CI: 3.97, 4.87), non-initiation of breastfeeding (AOR 0.39; 95 % CI: 0.36, 0.42), and with ever having a WFL >= 95th percentile (AOR 1.10; 95 % CI: 1.01, 1.20). Similar associations were noted for pregnancies involving unmarried women with paternal data, but differences were less pronounced. CONCLUSIONS: Missing paternal data on the birth certificate is associated with perinatal risk factors for childhood obesity. Efforts to understand and reduce obesity risk factors in early life may need to consider paternal factors. PMID- 27411309 TI - Living alone predicts mortality in patients with ischemic stroke before 70 years of age: a long-term prospective follow-up study. AB - BACKGROUND: Living alone is associated with increased mortality after myocardial infarction but little data is available about whether this applies to prognosis after stroke. We aimed to examine the association between living situation and long-term mortality in patients with ischemic stroke and a control group, and to explore whether this association is modified by patient gender. METHODS: This is a prospective case-control study of 600 patients with ischemic stroke before 70 years of age and 600 age- and sex-matched controls who have been included in the Sahlgrenska Study on Ischemic Stroke. Mortality data were collected through national registers and medical records. We used Cox regression models for identifying predictors of mortality. RESULTS: In the entire sample, mean age was 57 years, proportion of males 64%, proportion living alone 28%, and median follow up 8.6 years. Mortality rates were 36% among patients living alone, 17% among cohabitant patients, 15% among controls living alone, and 9% among cohabitant controls. Living alone was an independent predictor of all-cause mortality in cases after adjustment for stroke severity, stroke subtype, and vascular risk factors including physical activity, alcohol consumption, and socioeconomic status. A significant interaction was found between gender and living situation; the adjusted hazard ratio for mortality was 3.47 (95% Confidence Interval 2.13 5.65) in male patients living alone, whereas no significant association was observed in women. Living alone was also a predictor of vascular mortality among cases and of all-cause mortality among controls. CONCLUSIONS: Living alone is associated with increased long-term mortality after ischemic stroke in men. Further prospective studies are needed to confirm the observed gender difference and to identify modifiable factors underlying this increased risk. PMID- 27411310 TI - Effectiveness and safety of moxibustion for primary insomnia: a systematic review and meta-analysis. AB - BACKGROUND: Primary insomnia is a widespread and refractory disease. Moxibustion therapy for insomnia shows some advantages compared with conventional therapies. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effectiveness and safety of moxibustion therapy for insomnia. METHODS: We conducted a comprehensive literature review of the CENTRAL, PubMed, EMBASE, Web of science, CNKI, VIP, and Wanfang Data databases from their inception to July 2015 for RCTs that compared moxibustion with western medications, oral Chinese medicine, or other methods of traditional Chinese medicine (TCM) in patients with primary insomnia. The primary outcome measure was effective rate and secondary outcome measure was adverse events. Data collection and analysis included risk of bias evaluation, meta-analysis, sensitivity analysis, publication bias and adverse events analysis according to corresponding criteria. RESULTS: The study included 22 RCTs (1,971 patients). The quality of the studies was low. The overall meta-analysis demonstrated that moxibustion was more effective for insomnia than western medications, oral Chinese medicine and other TCM therapies (RR = 1.17, 95 % CI 1.12 to 1.23, P < 0.00001). Subgroup analyses demonstrated that moxibustion was more effective for insomnia than western medications (RR = 1.16, 95 % CI 1.09 to 1.24, P < 0.00001), oral Chinese medicine (RR = 1.11, 95 % CI 1.04 to 1.18, P = 0.002), and other TCM therapies (RR = 1.22, 95 % CI 1.15 to 1.30, P < 0.00001). There were no serious adverse effects associated with moxibustion therapy for insomnia, and the rate of adverse events was low. CONCLUSION: It is difficult to get the conclusion regarding the effectiveness and safety of moxibustion for primary insomnia due to insufficient evidence, such as the high risk of bias in the included studies, small sample sizes, and few reports on adverse effects. Moxibustion should be considered as a novel therapeutic option for insomnia, and more rigorous clinical trials of moxibustion therapy for insomnia are needed to assess its effects. PMID- 27411311 TI - Human cytomegalovirus miR-UL112-1 promotes the down-regulation of viral immediate early-gene expression during latency to prevent T-cell recognition of latently infected cells. AB - Human cytomegalovirus, a member of the herpesvirus family, can cause significant morbidity and mortality in immune compromised patients resulting from either primary lytic infection or reactivation from latency. Latent infection is associated with a restricted viral transcription programme compared to lytic infection which consists of defined protein coding RNAs but also includes a number of virally encoded microRNAs (miRNAs). One of these, miR-UL112-1, is known to target the major lytic IE72 transcript but, to date, a functional role for miR UL112-1 during latent infection has not been shown. To address this, we have analysed latent infection in myeloid cells using a virus in which the target site for miR-UL112-1 in the 3' UTR of IE72 was removed such that any IE72 RNA present during latent infection would no longer be subject to regulation by miR-UL112-1 through the RNAi pathway. Our data show that removal of the miR-UL112-1 target site in IE72 results in increased levels of IE72 RNA in experimentally latent primary monocytes. Furthermore, this resulted in induction of immediate early (IE) gene expression that is detectable by IE-specific cytotoxic T-cells (CTLs); no such CTL recognition of monocytes latently infected with wild-type virus was observed. We also recapitulated these findings in the more tractable THP-1 cell line model of latency. These observations argue that an important role for miR UL112-1 during latency is to ensure tight control of lytic viral immediate early (IE) gene expression thereby preventing recognition of latently infected cells by the host's potent pre-existing anti-viral CTL response. PMID- 27411314 TI - Butterfly myringoplasty for total, subtotal, and annular perforations. AB - OBJECTIVES/HYPOTHESIS: The inlay "butterfly" cartilage tympanoplasty was first described as a treatment for small, central ear drum perforations. This technique can also be applied in large, marginal perforations, whereas the cartilage graft is anchored on the bony annulus. The aim of this study was to present the technique, to evaluate the results of butterfly tympanoplasty in marginal perforations, and to compare with the results of butterfly tympanoplasty in patients with nonmarginal perforations. STUDY DESIGN: Retrospective case series. METHODS: The files of patients who underwent inlay butterfly cartilage tympanoplasty for subtotal and total perforations from May 2011 to May 2013 were reviewed. Patients were followed with otoscopy and audiometry, and their results were compared with those of patients who underwent butterfly tympanoplasty for nonmarginal perforations. RESULTS: Forty-eight patients underwent butterfly tympanoplasty for subtotal and total perforations during the study period. Exclusion criteria included: active inflammation during the 3 months prior to surgery, cholesteatoma, lack of follow-up, incomplete data, ossicular chain anomaly/discontinuity, and significant sensorineural hearing loss (average bone conduction threshold at 500,1000 and 2,000 Hz poorer than 20 dB). Thirty-three patients were included. The mean age at surgery was 34 years (range, 19-76 years); 17 patients (51%) were male. Four patients were treated previously by tympanoplasty (revision surgery), whereas the other 29 had primary surgery. None of the patients had intraoperative or immediate postoperative complications such as sensorineural hearing loss on the operated ear or facial nerve palsy. One month after surgery, two patients had a residual perforation (94% success rate), and the mean speech recognition threshold (SRT) improved from 38 dB to 24 dB. The pure tone audiogram improved from 37.7 dB to 10.6 dB, and the word recognition score improved from 97.7 to 99.75. These results are comparable with our results in nonmarginal perforations, whereas a 92% success rate and a postoperative SRT of 26 dB were achieved in a cohort of 42 patients. CONCLUSIONS: Inlay butterfly cartilage tympanoplasty is safe and effective in patients with total or subtotal perforations, and the results are comparable to those seen in nonmarginal perforations. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2565-2568, 2016. PMID- 27411313 TI - Live attenuated Salmonella displaying HIV-1 10E8 epitope on fimbriae: systemic and mucosal immune responses in BALB/c mice by mucosal administration. AB - The HIV-1 membrane proximal external region (MPER) that is targeted by several broadly neutralizing antibodies (BNAbs) has been considered a potential immunogen for vaccine development. However, to date the immunogenicity of these BNAb epitopes has not been made sufficiently adequate. In the present work, we used live attenuated Salmonella as a platform to present the HIV-1 MPER 10E8 epitope in the fimbriae. The insertion of the 10E8 epitope into the fimbriae had no significant influence on the expression and the absorption capacity of bacterial fimbriae, nor on the virulence and invasiveness of the attenuated Salmonella. After oral administration of the vaccine construct to mice followed by 10E8 epitope peptide boost, specific antibody responses in serum and mucosa as well as memory lymphocytes in spleen and plasma cells in bone marrow were induced. We also found that the live attenuated Salmonella vector directed the immunity toward Th1 bias, induced Th1 and Th2 cytokine responses and stimulated significant B cell differentiation into GC B, memory B and plasma cells. Therefore, we propose that the live attenuated Salmonella constitutively expressing HIV-1 BNAb epitopes on the fimbriae will be an effective approach to improving immune microenvironment and enhancing the immunogenicity of HIV-1 epitope vaccines. PMID- 27411315 TI - Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease. AB - BACKGROUND: The aim of this study was to elucidate the function of circulating follicular helper T (Tfh) cell subsets in helping B cells in patients with active, untreated IgG4-related disease (IgG4-RD) and determine their relationship with disease activity. METHODS: Seventeen consecutive patients with active, untreated IgG4-RD, 20 with primary Sjogren syndrome (pSS), 5 with multicentric Castleman's disease (MCD), and 12 healthy controls (HC) were enrolled. Tfh cell subset function was evaluated by co-culture with naive B cells in vitro. Activated Tfh cell subsets were defined as a CCR7(low)PD-1(high) subset among Tfh cell subsets. Disease activity was evaluated by IgG4-RD responder index (IgG4-RD RI) score. RESULTS: The number of Tfh2 cells was significantly higher in IgG4-RD compared to pSS, MCD, or HC, and correlated with serum IgG4 level or the number of plasmablasts. In vitro, Tfh2 cells more efficiently induced the differentiation of naive B cells into plasmablasts compared to Tfh1 or Tfh17 cells. Of note, while IgG production in culture supernatants of Tfh2 cells was comparable between IgG4-RD and HC, IgG4 production was significantly higher with Tfh2 cells from patients with IgG4-RD than in those from HC. Accordingly, the IgG4:IgG ratio in culture supernatants was also significantly higher with Tfh2 cells from IgG4-RD compared to HC. Moreover, the number of activated Tfh2 cells was higher in IgG4-RD compared to pSS, MCD, or HC, and strongly correlated with IgG4-RD RI score in the baseline active phase. Particularly, the number of activated Tfh2 cells was associated with the number of affected organs and serum IgG4 level. Importantly, the number of activated Tfh2 cells was decreased after glucocorticoid treatment and paralleled disease improvement. Moreover, the number of activated Tfh1 cells was also increased in IgG4-RD compared to pSS, MCD, or HC, correlating with IgG4-RD RI score, but not with serum IgG4 level. CONCLUSIONS: Tfh2 cells, but not Tfh1 or Tfh17 cells, induce the differentiation of naive B cells into plasmablasts and enhanced production of IgG4 in patients with active, untreated IgG4-RD. Furthermore, activated Tfh2 cells reflect disease activity, suggesting the involvement of this T cell subset in the pathogenesis of IgG4-RD. Interestingly, the number of activated Tfh1 cells was also increased in IgG4-RD, correlating with disease activity but not with serum IgG4 level, suggesting the involvement of Tfh1 cells but not in the process of IgG4 production in patients with IgG4-RD. PMID- 27411316 TI - Rationale, design and protocol of a longitudinal study assessing the effect of total knee arthroplasty on habitual physical activity and sedentary behavior in adults with osteoarthritis. AB - BACKGROUND: Physical activity levels are decreased and sedentary behaviour levels are increased in patients with knee osteoarthritis (OA). However, previous studies have shown that following total knee arthroplasty (TKA), objectively measured physical activity levels do not change compared to before the surgery. Very few studies have objectively assessed sedentary behaviour following TKA. This study aims to assess patterns of objective habitual physical activity and sedentary behaviour in patients with knee OA and to determine whether these change following TKA. METHODS: Patients diagnosed with knee osteoarthritis and scheduled for unilateral primary total knee arthroplasty will be recruited from the Orthopaedic Division at the Charlotte Maxeke Johannesburg Academic Hospital. Eligible participants will have assessments completed one week before the scheduled arthroplasty, six weeks, and six months post-operatively. The primary outcomes are habitual physical activity and sedentary behaviour which will be measured using accelerometry (Actigraph GTX3+ and activPal monitors) at the specific time points. The secondary outcomes will be improvements in osteoarthritis-specific quality of life measures using the following questionnaires: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), Knee Society Clinical Rating System (KSS), UCLA activity index; subjective pain scores, and self reported sleep quality. DISCUSSION: The present study will contribute to the field of musculoskeletal health by providing a rich detailed description of the patterns of accumulation of physical activity and sedentary behaviour in patients with knee OA. These data will contribute to existing knowledge using an objective measurement for the assessment of functional ability after total knee arthroplasty. Although studies have used accelerometry to measure physical activity in knee OA patients, the data provided thus far have not delved into the detailed patterns of how and when physical activity is accumulated before and after TKA. Accurate assessment of physical activity is important for physical activity interventions that target special populations. TRIAL REGISTRATION: NCT02675062 (4 February 2016). PMID- 27411317 TI - Network analysis and juvenile idiopathic arthritis (JIA): a new horizon for the understanding of disease pathogenesis and therapeutic target identification. AB - Juvenile idiopathic arthritis (JIA) is a clinically diverse and genetically complex autoimmune disease. Currently, there is very limited understanding of the potential underlying mechanisms that result in the range of phenotypes which constitute JIA.The elucidation of the functional relevance of genetic associations with phenotypic traits is a fundamental problem that hampers the translation of genetic observations to plausible medical interventions. Genome wide association studies, and subsequent fine-mapping studies in JIA patients, have identified many genetic variants associated with disease. Such approaches rely on 'tag' single nucleotide polymorphisms (SNPs). The associated SNPs are rarely functional variants, so the extrapolation of genetic association data to the identification of biologically meaningful findings can be a protracted undertaking. Integrative genomics aims to bridge the gap between genotype and phenotype.Systems biology, principally through network analysis, is emerging as a valuable way to identify biological pathways of relevance to complex genetic diseases. This review aims to highlight recent findings in systems biology related to JIA in an attempt to assist in the understanding of JIA pathogenesis and therapeutic target identification. PMID- 27411318 TI - Roles of Na(+)/Ca(2+) exchanger isoforms NCX1 and NCX2 in motility in mouse ileum. AB - The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1 heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP. PMID- 27411320 TI - Wickerhamiella brachini f.a., sp. nov., Wickerhamiella pterostichi f.a., sp. nov. and Wickerhamiella qilinensis f.a., sp. nov., three yeast species isolated from insects. AB - Eight strains representing three novel yeast species were isolated from insects distributed in three localities in Nanyang, Henan Province, Central China during 2014 and 2015. Sequence analysis of the D1/D2 domains of the large subunit (LSU) rRNA gene revealed that these species are members of the Wickerhamiella clade. These three novel species have a greater than 2.5 % difference from each other or their closest known species in the D1/D2 sequences. The three yeast species can also be separated from their closest known species in terms of physiological characteristics. Moreover, a sexual state could not be found in these three novel yeast species on various sporulation media. Therefore, the three novel species are described as Wickerhamiella brachini f.a., sp. nov. (type strain, NYNU 15885T=CICC 33092T=CBS 14176T), Wickerhamiellapterostichi f.a., sp. nov. (type strain, NYNU 15896T=CICC 33093T=CBS 14177T) and Wickerhamiellaqilinensis f.a., sp. nov. (type strain, NYNU 146103T=CICC 33062T=CBS 13929T). The MycoBank numbers of Wickerhamiella brachini f.a., sp. nov., Wickerhamiellapterostichi f.a., sp. nov. and Wickerhamiellaqilinensis f.a., sp. nov. are MB 816962, MB 816963 and MB 816964, respectively. PMID- 27411321 TI - Models of In-Vivo Bacterial Infections for the Development of Antimicrobial Peptide-based Drugs. AB - The increasing frequency of multi-resistant Gram-positive and Gram-negative bacteria and a long-term decreasing trend in the development of new antimicrobial molecules prompts research for new anti-infective agents with new modes of action. Antimicrobial peptides (AMPs) are considered an interesting class of antibacterial molecules. Many new AMPs have been discovered and some are being evaluated for the development of new antibacterial therapeutics. Since the development of new antibacterial drugs has been neglected for decades, we are now faced with extreme medical need combined with a lack of technical experimental progress in setting up efficient models of antibacterial activity in animals. Here we review experiments with AMPs in animal models of sepsis, pneumonia and skin infection caused by bacteria. Animal models of infection have been of enormous predictive value in antibacterial drug discovery, both for elucidating AMP efficacy in the treatment of experimentally induced infection and for comparing the effectiveness of two or more antibiotics. PMID- 27411319 TI - Pros and Cons of Clinical Basophil Testing (BAT). AB - PURPOSE OF REVIEW: We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages. RECENT FINDINGS: There are many tools available to assess the presence and severity of allergic diseases in patients. For 50 years, peripheral blood basophils have been used as tools to study these diseases. It is a very accessible cell that binds IgE antibody and secretes the classical mediators responsible for the symptoms of allergic reactions. In the last decade, an even more accessible methodology, using flow cytometry, has been developed to enhance the ability to use basophils for both mechanistic and clinical diagnostics. Basophil testing has been included in diagnostics for different forms of allergies as well as to monitor disease status. A variety of studies have begun to establish both precise methods and their clinical relevance for disease diagnosis, but there remain some important questions on how to take optimal advantage of the behaviours of basophils. PMID- 27411322 TI - Antimicrobial Peptides Under Clinical Trials. AB - Today microbial drug resistance has become a serious problem not only within inpatient setting but also within outpatient setting. Repeated intake and unnecessary usage of antibiotics as well as the transfer of resistance genes are the most important factors that make the microorganisms resistant to conventional antibiotics. A large number of antimicrobials successfully used for prophylaxis and therapeutic purposes have now become ineffective [1, 2]. Therefore, new molecules are being studied to be used in the treatment of various diseases. Some of these molecules are structural compounds based on a combination of peptides, for example, naturally occurring endogenous peptide antibiotics and their synthetic analogues or molecules designed de novo using QSAR (quantitative structureproperty relationships)-based methods [3]. Trying to exploit numerous advantages of antimicrobial peptides such as high potency and selectivity, broad range of targets, potentially low toxicity and low accumulation in tissues, pharmaceutical industry aims to develop them as commercially available drugs and appropriate clinical trials are being conducted [4]. In this paper we define clinical trials steps and describe current status of several antimicrobial peptides under clinical development as well as briefly depict peptide drug formulation. PMID- 27411323 TI - Antimicrobial Peptides as a Strategy to Combat Fungal Biofilms. AB - Invasive fungal infections caused by opportunistic fungal pathogens are associated with high mortality rates, mainly due to the occurrence of genotypic and/or phenotypic resistance. One of the causes of phenotypic resistance is the preferred growth of various fungal pathogens as biofilms, which are tolerant or resistant to most classes of antifungal agents. Moreover, increasing evidence points to biofilm formation as a general prerequisite for the development of systemic infections. Therefore, new antibiofilm agents are urgently needed to reduce the incidence of biofilm-associated infections. Nowadays, antimicrobial peptides (AMPs) are considered as valuable alternatives for or complements to the classical antifungal agents to combat fungal infections. Many review reports describe activity of AMPs against free-living planktonic fungal pathogens. In contrast, this review summarizes the antibiofilm properties of natural or synthetic AMPs against fungal biofilms and their potential to enhance the antibiofilm activity of existing antifungal agents. PMID- 27411324 TI - Antimicrobial Peptides as Anti-biofilm Agents in Medical Implants. AB - Biofilm-associated infections constitute a daunting threat to human health, since these pathologies increase patient mortality and morbidity, resulting in prolonged hospitalization periods and heavy economic losses. Moreover, these infections contribute to the increasing emergence and dissemination of antibiotic resistance in hospitals and in the community. Although biofilm-associated microorganisms can proliferate in healthy tissue, abiotic surfaces like those of medical implants greatly increase the likelihood of biofilm formation in the host. Due to their broad spectrum of bactericidal activity against multi-drug resistant microorganisms including metabolically inactive cells, antimicrobial peptides (AMPs) have great potential as anti-biofilm agents. In fact, a clinically available AMP, polymyxin E (colistin), frequently constitutes the drug of last recourse in biofilm-associated infections (e.g. cystic fibrosis) when resistance to all the other drugs arises. In this article, we outline the main strategies under development to combat biofilm-associated infections with an emphasis in the prevention of microbial colonization of medical implants. These approaches include the use of AMPs both for the development of anti-adhesive surface coatings and to kill biofilm-forming cells either on contact or via controlled release (leaching surfaces). Although in vitro results for all these applications are very encouraging, further research is needed to improve the anti biofilm activity of these coatings in vivo. The possibility of exploiting the antibiotic potentiating activity of some AMPs and to combine several anti-biofilm mechanisms in tandem targeting the biofilm formation process at different stages is also discussed. PMID- 27411325 TI - Mimics of Host Defense Proteins; Strategies for Translation to Therapeutic Applications. AB - New infection treatments are urgently needed to combat the rising threat of multi drug resistant bacteria. Despite early clinical set-backs attention has re focused on host defense proteins (HDPs), as potential sources for new and effective antimicrobial treatments. HDPs appear to act at multiple targets and their repertoire includes disruptive membrane and intracellular activities against numerous types of pathogens as well as immune modulatory functions in the host. Importantly, these novel activities are associated with a low potential for emergence of resistance and little crossresistance with other antimicrobial agents. Based on these properties, HDPs appear to be ideal candidates for new antibiotics; however, their development has been plagued by the many therapeutic limitations associated with natural peptidic agents. This review focuses on HDP mimetic approaches aimed to improve metabolic stability, pharmacokinetics, safety and manufacturing processes. Early efforts with beta-peptide or peptoid analogs focused on recreating stable facially amphiphilic structures but demonstrated that antimicrobial activity was modulated by more, complex structural properties. Several approaches have used lipidation to increase the hydrophobicity and membrane activity. One lead compound, LTX-109, has entered clinical study as a topical agent to treat impetigo and nasal decolonization. In a more significant departure from the amino acid like peptidomimetics, considerable effort has been directed at developing amphiphilic compounds that recapitulate the structural and biological properties of HDPs on small abiotic scaffolds. The lead compound from this approach, brilacidin, has completed two phase 2 studies as an intravenous agent for skin infections. PMID- 27411326 TI - Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides. AB - The increasing rates of resistance among bacteria and to a lesser extent fungi have resulted in an urgent need to find new molecules that hold therapeutic promise against multidrug-resistant strains. Antimicrobial peptides have proven very effective against a variety of multidrug-resistant bacteria. Additionally, the low levels of resistance reported towards these molecules are an attractive feature for antimicrobial drug development. Here we summarise information on diverse peptide libraries used to discover or to optimize antimicrobial peptides. Chemical synthesized peptide libraries, for example split and mix method, tea bag method, multi-pin method and cellulose spot method are discussed. In addition biological peptide library screening methods are summarized, like phage display, bacterial display, mRNA-display and ribosomal display. A few examples are given for small peptide libraries, which almost exclusively follow a rational design of peptides of interest rather than a combinatorial approach. PMID- 27411327 TI - The Medical Potential of Antimicrobial Peptides from Insects. AB - Antimicrobial peptides (AMPs) are peptide-based effector molecules produced by the innate immune system to combat microbes. Insects produce the broadest repertoire of AMPs, and their potent antimicrobial activity in vitro and in vivo has promoted their development as alternatives to conventional antibiotics, in an attempt to address the threat of multidrug-resistant pathogens. Here we discuss current obstacles that hinder the therapeutic development of novel insect-derived AMPs, including potential cytotoxic, immunogenic and allergenic side effects, and the high costs of large-scale production. These challenges may be overcome by the falling costs of synthetic peptide analogs and the heterologous production of recombinant peptides in insect cells or plants (molecular pharming). Insect AMPs offer a promising alternative for the treatment of skin, eye and lung infections, and could also restore the susceptibility of multidrug-resistant pathogens to conventional antibiotics when used as combinatorial treatments. Insect AMPs can also be used as templates for the rational design of peptide mimetics to overcome the drawbacks of natural therapeutic peptides. PMID- 27411328 TI - Elucidating Unusual Modes of Action and Resistance of Antibacterial Peptides. AB - The emergence of bacterial resistance to conventional antibiotics has been become a major issue in the health system. Currently, studies are being performed to develop new drugs that can replace conventional antibiotics. These new drugs include the antimicrobial peptides (AMPs), a heterogeneous group of molecules produced in a variety of bacterial, invertebrate, plant and animal species, which can serve as a nonspecific defense system that complements the highly specific cell-mediated immune response. AMPs have antimicrobial activities against a wide range of microorganisms, including bacteria, fungi, and viruses, and they are effective against pathogenic organisms that are resistant to common drugs. The most common mechanism of action of antibacterial peptides on microbial cells has been characterized as an alteration in the cellular membrane permeability. In contrast, there are AMPs with unusual strategies associated with cell wall and protein synthesis inhibition, nucleic acid binding or inactivation of toxins that enable microbial infection. Many pathogens can develop resistance strategies, inactivating or repelling AMPs through modification of the surface expression of pumps or secretion of proteases. In summary, this review focus on AMPs with non conventional modes of actions and the microbial counter measures to resist these peptides. PMID- 27411329 TI - Membrane-active Antimicrobial Peptides as Template Structures for Novel Antibiotic Agents. AB - The increase of pathogens being resistant to antibiotics represents a global health problem and thus, there is an urgent need for the development of antibiotics with novel mechanisms of action. Host defense peptides, which have direct antimicrobial activity (also termed antimicrobial peptides) or immune modulating activity, are valuable template structures for the development of such compounds. Antimicrobial peptides exhibit remarkably different structures as well as biological activity profiles with multiple targets. A large fraction of these peptides interfere physically with the cell membrane of bacteria (focus of this review), but can also translocate into the cytosol, where they interact with nucleic acids, ribosomes and proteins. Several potential interaction sites have to be considered on the route of the peptides from the environment to the cytoplasmic membrane. Translocation of peptides through the cell wall may not be impaired by the thick but relatively porous peptidoglycan layer. However, interaction with lipopolysaccharides of the outer membrane of Gram-negative bacteria and (lipo)teichoic acids of Gram-positive bacteria may reduce the effective concentration at the cytoplasmic membrane, where supposedly the killing event takes place. On a molecular level several mechanisms are discussed, which are important for the rational design of improved antimicrobial compounds: toroidal pore formation, carpet model (coverage of membrane surface by peptides), interfacial activity, void formation, clustering of lipids and effects of membrane curvature. In summary, many of these models just represent special cases that can be interrelated to each other and depend on the nature of lipids and peptides. PMID- 27411330 TI - Assessing the accuracy of using oscillating gradient spin echo sequences with AxCaliber to infer micron-sized axon diameters. AB - OBJECTIVE: Current magnetic resonance imaging (MRI) axon diameter measurements rely on the pulsed gradient spin-echo sequence, which is unable to provide diffusion times short enough to measure small axon diameters. This study combines the AxCaliber axon diameter fitting method with data generated from Monte Carlo simulations of oscillating gradient spin-echo sequences (OGSE) to infer micron sized axon diameters, in order to determine the feasibility of using MRI to infer smaller axon diameters in brain tissue. MATERIALS AND METHODS: Monte Carlo computer simulation data were synthesized from tissue geometries of cylinders of different diameters using a range of gradient frequencies in the cosine OGSE sequence . Data were fitted to the AxCaliber method modified to allow the new pulse sequence. Intra- and extra-axonal water were studied separately and together. RESULTS: The simulations revealed the extra-axonal model to be problematic. Rather than change the model, we found that restricting the range of gradient frequencies such that the measured apparent diffusion coefficient was constant over that range resulted in more accurate fitted diameters. Thus a careful selection of frequency ranges is needed for the AxCaliber method to correctly model extra-axonal water, or adaptations to the method are needed. This restriction helped reduce the necessary gradient strengths for measurements that could be performed with parameters feasible for a Bruker BG6 gradient set. For these experiments, the simulations inferred diameters as small as 0.5 MUm on square-packed and randomly packed cylinders. The accuracy of the inferred diameters was found to be dependent on the signal-to-noise ratio (SNR), with smaller diameters more affected by noise, although all diameter distributions were distinguishable from one another for all SNRs tested. CONCLUSION: The results of this study indicate the feasibility of using MRI with OGSE on preclinical scanners to infer small axon diameters. PMID- 27411331 TI - The "ick" Factor Matters: Disgust Prospectively Predicts Avoidance in Chemotherapy Patients. AB - BACKGROUND: Chemotherapy can be physically and psychologically demanding. Avoidance and withdrawal are common among patients coping with these demands. PURPOSE: This report compares established emotional predictors of avoidance during chemotherapy (embarrassment; distress) with an emotion (disgust) that has been unstudied in this context. METHODS: This report outlines secondary analyses of an RCT where 68 cancer patients undergoing chemotherapy were randomized to mindfulness or relaxation interventions. Self-reported baseline disgust (DS-R), embarrassment (SES-SF), and distress (Distress Thermometer) were used to prospectively predict multiple classes of avoidance post-intervention and at 3 months follow-up. Measures assessed social avoidance, cognitive and emotional avoidance (IES Avoidance), as well as information seeking and treatment adherence (General Adherence Scale). RESULTS: Repeated-measures ANOVAs evaluated possible longitudinal changes in disgust and forward entry regression models contrasted the ability of the affective variables to predict avoidance. Although disgust did not change over time or vary between groups, greater disgust predicted greater social, cognitive, and emotional avoidance, as well as greater information seeking. Social avoidance was predicted by trait embarrassment and distress predicted non-adherence. CONCLUSIONS: This report represents the first investigation of disgust's ability to prospectively predict avoidance in people undergoing chemotherapy. Compared to embarrassment and distress, disgust was a more consistent predictor across avoidance domains and its predictive ability was evident across a longer period of time. Findings highlight disgust's role as an indicator of likely avoidance in this health context. Early identification of cancer patients at risk of deleterious avoidance may enable timely interventions and has important clinical implications (ACTRN12613000238774). PMID- 27411332 TI - New program for identification of child maltreatment in emergency department: preliminary data. AB - Early detection of child maltreatment in pediatric emergency department is one of the most important challenges for the Italian and European medical care system. Several interventions have been proposed, but results are often unquantifiable or inadequate to face this problem. We promoted an educational program and built up an interdisciplinary team to improve the identification and management of maltreated children. Aim of this study is to report preliminary results of these interventions. Meetings structured with lecture-based teaching and case-based lessons were focused on identification and management of maltreatment cases. An interdisciplinary team with forensic physicians, dermatologists, orthopedics, radiologists, gynecologists, oculists, psychologists and psychiatrics, was created to manage children with suspected diagnosis of maltreatment. We analysed the characteristics of subjects diagnosed after these interventions and their number was compared with the one in the two previous years. An increased rate of diagnoses of 16.9 % was found. Results of the reported program are encouraging, but many efforts are still mandatory to improve the child maltreatment identification in emergency departments. PMID- 27411333 TI - A novel multivariate STeady-state index during general ANesthesia (STAN). AB - The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study. PMID- 27411334 TI - Improved production of tannase by Klebsiella pneumoniae using Indian gooseberry leaves under submerged fermentation using Taguchi approach. AB - Tannase (tannin acyl hydrolase E.C 3.1.1.20) is an inducible, largely extracellular enzyme that causes the hydrolysis of ester and depside bonds present in various substrates. Large scale industrial application of this enzyme is very limited owing to its high production costs. In the present study, cost effective production of tannase by Klebsiella pneumoniae KP715242 was studied under submerged fermentation using different tannin rich agro-residues like Indian gooseberry leaves (Phyllanthus emblica), Black plum leaves (Syzygium cumini), Eucalyptus leaves (Eucalyptus glogus) and Babul leaves (Acacia nilotica). Among all agro-residues, Indian gooseberry leaves were found to be the best substrate for tannase production under submerged fermentation. Sequential optimization approach using Taguchi orthogonal array screening and response surface methodology was adopted to optimize the fermentation variables in order to enhance the enzyme production. Eleven medium components were screened primarily by Taguchi orthogonal array design to identify the most contributing factors towards the enzyme production. The four most significant contributing variables affecting tannase production were found to be pH (23.62 %), tannin extract (20.70 %), temperature (20.33 %) and incubation time (14.99 %). These factors were further optimized with central composite design using response surface methodology. Maximum tannase production was observed at 5.52 pH, 39.72 degrees C temperature, 91.82 h of incubation time and 2.17 % tannin content. The enzyme activity was enhanced by 1.26 fold under these optimized conditions. The present study emphasizes the use of agro-residues as a potential substrate with an aim to lower down the input costs for tannase production so that the enzyme could be used proficiently for commercial purposes. PMID- 27411335 TI - Prognoses of new complete dentures from the patient's denture assessment of existing dentures. AB - OBJECTIVES: The aim was to determine prognostic factors affecting frequent post delivery adjustments of new complete dentures using patients' assessments of existing complete dentures. MATERIALS AND METHODS: A total of 125 edentulous participants (56 men, 69 women; mean age, 76.4 years) who required new complete dentures evaluated existing dentures using the patient's denture assessment (PDA), a questionnaire regarding the self-assessment of dentures composed of 22 question items and containing six subscales: "function," "lower denture," "upper denture," "expectation," "esthetics and speech," and "importance." Moreover, the numbers of post-delivery adjustments of new dentures were recorded. A multiple logistic regression analysis was performed to identify significant factors for frequent adjustments of new dentures with five subscales of the PDA (excluding "importance"), level of mandibular ridge resorption, and age as independent variables. RESULTS: The analysis showed that "function," "esthetics and speech," and level of mandibular ridge resorption were significant variables for a frequent number of post-delivery adjustments of new complete dentures. CONCLUSIONS: The results suggested that patients' assessments of existing dentures using the PDA might allow a prediction of prognosis for complete denture treatments. Additionally, low "function" scores and high "esthetics and speech" scores for existing dentures and high levels of mandibular ridge resorption were significant prognostic factors affecting frequent post-delivery adjustments of new complete dentures. CLINICAL RELEVANCE: It may be difficult for edentulous persons to adapt to new complete dentures, especially those who have complaints about mastication and swallowing with existing dentures and poor mandibular ridges, but are satisfied with esthetics and speech. PMID- 27411336 TI - Zinc finger proteins in cancer progression. AB - Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression. PMID- 27411337 TI - Sonographic evaluation of tongue motions during upper airway stimulation for obstructive sleep apnea-a pilot study. AB - INTRODUCTION: The objective was to evaluate the feasibility of sonographic evaluation of functional tongue motion as a tool to evaluate postoperative outcomes in human subjects using breathing-synchronized stimulation of the hypoglossal nerve-a novel therapy option for patients with obstructive sleep apnea (OSA). MATERIAL AND METHODS: Sixteen patients with OSA (n = 16, age 60.4 +/ 10.2, BMI 28.7 +/- 2.4, AHI 35.0 +/- 11.8) underwent sonographic evaluation of tongue motion after initiation of therapy with the Inspire II Upper Airway Stimulation system. Sonographic examination was performed in four different planes (A = floor of the mouth frontal, B = base of the tongue horizontal, C = floor of the mouth parallel to mandible, and D = floor of the mouth median sagittal) in an attempt to visualize tongue surface, tongue and hyoid motion, and the distance of protrusion. RESULTS: Identification of the tongue surface was achieved in all cases in planes B, C, and D and 81 % of patients in plane A. Tongue motion was evident on the right (implant) side in 63 % in plane A and 75 % in plane B. Distance of protrusion was measured in plane B at 1.04 cm (+/-0.51), in plane C at 1.08 cm (+/-0.47), and in plane D at 0.96 cm (+/-0.45). Hyoid protrusion was measured in plane C or D and was 0.57 cm (+/-0.39). Significant correlations among the three planes were observed, but there was no correlation to the reduction of apnea-hypopnea index. CONCLUSION: The results indicate feasibility of sonography to identify tongue and hyoid motions during upper airway stimulation. Useful sonographic planes and landmarks, which allow visualization of dynamic effects of upper airway stimulation, could be established. The evaluation of the tongue in a horizontal (B) and in a sagittal plane (D) appears to be superior to the other investigated planes. The approximate tongue protrusion needed to generate a significant reduction of AHI and ODI was 1 cm. PMID- 27411338 TI - Support vector machines for automated snoring detection: proof-of-concept. AB - BACKGROUND: Snoring has been shown to be associated with adverse physical and mental health, independent of the effects of sleep disordered breathing. Despite increasing evidence for the risks of snoring, few studies on sleep and health include objective measures of snoring. One reason for this methodological limitation is the difficulty of quantifying snoring. Conventional methods may rely on manual scoring of snore events by trained human scorers, but this process is both time- and labor-intensive, making the measurement of objective snoring impractical for large or multi-night studies. METHODS: The current study is a proof-of-concept to validate the use of support vector machines (SVM), a form of machine learning, for the automated scoring of an objective snoring signal. An SVM algorithm was trained and tested on a set of approximately 150,000 snoring and non-snoring data segments, and F-scores for SVM performance compared to visual scoring performance were calculated using the Wilcoxon signed rank test for paired data. RESULTS: The ability of the SVM algorithm to discriminate snore from non-snore segments of data did not differ statistically from visual scorer performance (SVM F-score = 82.46 +/- 7.93 versus average visual F-score = 88.35 +/- 4.61, p = 0.2786), supporting SVM snore classification ability comparable to visual scorers. CONCLUSION: In this proof-of-concept, we established that the SVM algorithm performs comparably to trained visual scorers, supporting the use of SVM for automated snoring detection in future studies. PMID- 27411339 TI - Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer's disease. AB - Sporadic Alzheimer's disease (AD) is characterised by the deposition and accumulation of specific protein aggregates. Failure of clearance could underlie this process, and recent genetic association studies point towards involvement of the phagocytosis and autophagy pathways. We developed a real-time tri-color flow cytometry method to quantitate the phagocytic function of human peripheral blood monocyte subsets including non-classic CD14(dim)CD16(+), intermediate CD14(+)CD16(+) and classic CD14(+)CD16(-) monocytes. Using this method, we have measured the phagocytic ability of fresh monocytes in a study of preclinical, prodromal and clinical AD, matched with cognitively normal healthy control subjects. Basal levels of phagocytosis in all three subsets of monocytes were similar between healthy controls and AD patients, while a significant increase of basal phagocytosis was found in subjects with high Abeta-amyloid burden as assessed by PET scans. Pre-treating cells with Copaxone (CPX, to stimulate phagocytosis) or ATP (an inhibitor of P2X7-mediated phagocytosis) showed a differential response depending on clinical or Abeta-burden status, indicating a relative functional deficit. Overall the results are consistent with a perturbation of basal and stimulated innate phagocytosis in sporadic AD. PMID- 27411340 TI - SURVIVIN as a marker for quiescent-breast cancer stem cells-An intermediate, adherent, pre-requisite phase of breast cancer metastasis. AB - Cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a breast cancer metastasis model and reported the existence of an adherent, distinct pre-metastatic phase, quiescent-breast cancer stem cells (Q BCSCs) prior to attaining an EMT. SURVIVIN was found to be expressed in Q-BCSCs. Time dependant biphasic expression of SURVIVIN in Q-BCSCs reveals that Q-BCSCs is a pre-metastatic phase distinct from both epithelial and mesenchymal counterparts. SURVIVIN favours metastasis and up-regulates WNT/beta-CATENIN pathway in a PI3 K/AKT-dependant manner for self-renewal. Knockdown of SURVIVIN in Q-BCSCs lost the metastatic property of cells by inhibiting invasion, EMT-MET, PI3 K/AKT/WNT cascade, and induced apoptosis. Thus, our data suggest the existence of a novel pre-metastatic phase (Q-BCSCs) before EMT and SURVIVIN acts as a marker for Quiescent-BCSCs. PMID- 27411341 TI - A C-type lectin with an immunoglobulin-like domain promotes phagocytosis of hemocytes in crayfish Procambarus clarkii. AB - C-type lectins are important immune molecules that participate in host defense response. The present work reports a novel C-type lectin (PcLec3) from the red swamp crayfish Procambarus clarkii. Sequence analysis found that PcLec3 encodes a polypeptide with252 amino acid residues, which contains an immunoglobulin-like domain (IG) and a C-type lectin domain (CTLD) arranged in tandem. Tissue distribution analysis indicated that PcLec3 is enriched expressed in hemocytes and hepatopancreas cells, in which PcLec3 was up-regulated following bacterial challenge by Vibrio anguillarum. Function analysis using recombinant full-length PcLec3, IG, and CTLD proteins revealed that these recombinant proteins had the capacity to bind carbohydrates and bacteria, while IG determined the cell binding activity. However, only full-length PcLec3 promotes the phagocytic activity of hemocytes and subsequent clearance of invasive bacteria. Taken together, these results manifest that PcLec3 acts as a hemocyte adhesion molecule to promote hemocyte phagocytosis against invasive V. anguillarum. PMID- 27411343 TI - "Bleak" future predicted for social care without urgent extra funding. PMID- 27411342 TI - Incremental Value of Two Dimensional Speckle Tracking Echocardiography in the Functional Assessment and Characterization of Subclinical Left Ventricular Dysfunction. AB - Subclinical left ventricular (LV) dysfunction refers to subtle abnormalities in LV function which typically precede a reduction in the left ventricular ejection fraction (LVEF). The assessment of myocardial function using LVEF, a radial metric of systolic function, is subject to load dependence, intra-observer and inter-observer variability. Reductions in LVEF typically manifest late in the disease process thus compromising the ability to intervene before irreversible impairment of systolic performance sets in. 2-Dimensional speckle tracking echocardiography (2D-STE), a novel strain imaging modality has shown promise as a sensitive indicator of myocardial contractility. It arms the clinician with a powerful and practical tool to rapidly quantify cardiac mechanics, circumventing several inherent limitations of conventional echocardiography. This article highlights the incremental utility of 2D-STE in the detection of subclinical LV dysfunction. PMID- 27411352 TI - Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study. AB - BACKGROUND: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study. METHODS: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs. RESULTS: A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer. CONCLUSION: C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk. IMPACT: C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348-55. (c)2016 AACR. PMID- 27411354 TI - The Development and Deployment of a Maintenance Operations Safety Survey. AB - OBJECTIVE: Based on the line operations safety audit (LOSA), two studies were conducted to develop and deploy an equivalent tool for aircraft maintenance: the maintenance operations safety survey (MOSS). BACKGROUND: Safety in aircraft maintenance is currently measured reactively, based on the number of audit findings, reportable events, incidents, or accidents. Proactive safety tools designed for monitoring routine operations, such as flight data monitoring and LOSA, have been developed predominantly for flight operations. METHOD: In Study 1, development of MOSS, 12 test peer-to-peer observations were collected to investigate the practicalities of this approach. In Study 2, deployment of MOSS, seven expert observers collected 56 peer-to-peer observations of line maintenance checks at four stations. Narrative data were coded and analyzed according to the threat and error management (TEM) framework. RESULTS: In Study 1, a line check was identified as a suitable unit of observation. Communication and third-party data management were the key factors in gaining maintainer trust. Study 2 identified that on average, maintainers experienced 7.8 threats (operational complexities) and committed 2.5 errors per observation. The majority of threats and errors were inconsequential. Links between specific threats and errors leading to 36 undesired states were established. CONCLUSION: This research demonstrates that observations of routine maintenance operations are feasible. TEM-based results highlight successful management strategies that maintainers employ on a day-to-day basis. APPLICATION: MOSS is a novel approach for safety data collection and analysis. It helps practitioners understand the nature of maintenance errors, promote an informed culture, and support safety management systems in the maintenance domain. PMID- 27411353 TI - Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. AB - The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in the spinal cord. Accordingly, we evaluated whether burn injury evoked the central release of oxidized lipids . Analysis of lipid extracts of spinal cord tissue with HPLC-MS revealed a significant increase in levels of the epoxide and diol metabolites of linoleic acid: 9,10-DiHOME, 12,13-DiHOME, 9(10)-EpOME, and 12(13)-EpOME, that was reduced after intrathecal (i.t.) injection of the oxidative enzyme inhibitor ketoconazole. Moreover, we found that these four lipid metabolites were capable of specifically activating both TRPV1 and TRPA1. Intrathecal injection of specific antagonists to TRPV1 (AMG-517) or TRPA1 (HC 030031) significantly reduced post-burn mechanical and thermal allodynia. Finally, i.t. injection of ketoconazole significantly reversed post-burn mechanical and thermal allodynia. Our data indicate that spinal cord TRPV1 and TRPA1 contributes to pain after burn and identifies a novel class of oxidized lipids elevated in the spinal cord after burn injury. Since the management of burn pain is problematic, these findings point to a novel approach for treating post-burn pain. PMID- 27411355 TI - Interferon regulatory factor 3 is a key regulation factor for inducing the expression of SAMHD1 in antiviral innate immunity. AB - SAMHD1 is a type I interferon (IFN) inducible host innate immunity restriction factor that inhibits an early step of the viral life cycle. The underlying mechanisms of SAMHD1 transcriptional regulation remains elusive. Here, we report that inducing SAMHD1 upregulation is part of an early intrinsic immune response via TLR3 and RIG-I/MDA5 agonists that ultimately induce the nuclear translocation of the interferon regulation factor 3 (IRF3) protein. Further studies show that IRF3 plays a major role in upregulating endogenous SAMHD1 expression in a mechanism that is independent of the classical IFN-induced JAK-STAT pathway. Both overexpression and activation of IRF3 enhanced the SAMHD1 promoter luciferase activity, and activated IRF3 was necessary for upregulating SAMHD1 expression in a type I IFN cascade. We also show that the SAMHD1 promoter is a direct target of IRF3 and an IRF3 binding site is sufficient to render this promoter responsive to stimulation. Collectively, these findings indicate that upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3 and we suggest that type I IFN induction and induced SAMHD1 expression are coordinated. PMID- 27411356 TI - Organ-specific SPECT activity calibration using 3D printed phantoms for molecular radiotherapy dosimetry. AB - BACKGROUND: Patient-specific absorbed dose calculations for molecular radiotherapy require accurate activity quantification. This is commonly derived from Single-Photon Emission Computed Tomography (SPECT) imaging using a calibration factor relating detected counts to known activity in a phantom insert. METHODS: A series of phantom inserts, based on the mathematical models underlying many clinical dosimetry calculations, have been produced using 3D printing techniques. SPECT/CT data for the phantom inserts has been used to calculate new organ-specific calibration factors for (99m) Tc and (177)Lu. The measured calibration factors are compared to predicted values from calculations using a Gaussian kernel. RESULTS: Measured SPECT calibration factors for 3D printed organs display a clear dependence on organ shape for (99m) Tc and (177)Lu. The observed variation in calibration factor is reproduced using Gaussian kernel-based calculation over two orders of magnitude change in insert volume for (99m) Tc and (177)Lu. These new organ-specific calibration factors show a 24, 11 and 8 % reduction in absorbed dose for the liver, spleen and kidneys, respectively. CONCLUSIONS: Non-spherical calibration factors from 3D printed phantom inserts can significantly improve the accuracy of whole organ activity quantification for molecular radiotherapy, providing a crucial step towards individualised activity quantification and patient-specific dosimetry. 3D printed inserts are found to provide a cost effective and efficient way for clinical centres to access more realistic phantom data. PMID- 27411357 TI - Time allocation and temporal focus in nursing management: an integrative review. AB - AIM: To describe the time allocation and temporal focus in nursing management. BACKGROUND: There is limited information about the time allocation and temporal focus of nursing management activities. The role of nurse administrators is changing, resulting in challenges related to time management. METHODS: Published literature in 2005-2014 related to the time allocation or temporal focus of nurse administrators' management activities was retrieved from five databases, and an integrative review was conducted. Data extraction, quality assessment and quantitative content analysis were performed for eight reviewed articles. RESULTS: Daily reactive management activities and administrative routines were dominant in the nurse administrators' work, and strategic, proactive activities were scarce. Their daily work was fragmented by a variety of activities and numerous interruptions. CONCLUSION: Little information exists about time allocation or temporal focus in nurse administrators' management activities. Further research on this topic is needed. The evidence was fairly modest, although the studies' results were generally similar. IMPLICATIONS FOR NURSING MANAGEMENT: These results can be used to clarify the job descriptions of nurse administrators and to plan and focus their education and training. Organisations need to use evidence to standardise the job descriptions of different levels of nurse managers and directors. PMID- 27411359 TI - Biological Reconstruction of the Osteochondral Unit After Failed Focal Resurfacing of a Chondral Defect in the Knee. PMID- 27411358 TI - Is There a Difference in Graft Motion for Bone-Tendon-Bone and Hamstring Autograft ACL Reconstruction at 6 Weeks and 1 Year? AB - BACKGROUND: Bone-patellar tendon-bone (BTB) grafts are generally believed to heal more quickly than soft tissue grafts after anterior cruciate ligament (ACL) reconstruction, but little is known about the time course of healing or motion of the grafts within the bone tunnels. HYPOTHESIS: Graft-tunnel motion will be greater in hamstring (HS) grafts compared with BTB grafts and will be less at 1 year than at 6 weeks. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve patients underwent anatomic single-bundle ACL reconstruction using HS or BTB autografts (6 per group) with six 0.8-mm tantalum beads embedded in each graft. Dynamic stereo x-ray images were collected at 6 weeks and 1 year during treadmill walking and stair descent and at 1 year during treadmill running. Tibiofemoral kinematics and bead positions were evaluated. Graft-tunnel motion was based on bead range of motion during the loading response phase (first 10%) of the gait cycle. RESULTS: During treadmill walking, there was no difference in femoral tunnel or tibial tunnel motion between BTB or HS grafts at 6 weeks (BTB vs HS: 2.00 +/- 1.05 vs 1.25 +/- 0.67 mm [femoral tunnel]; 1.20 +/- 0.63 vs 1.27 +/- 0.71 mm [tibial tunnel]), or 1 year (BTB vs HS: 1.62 +/- 0.76 vs 1.08 +/- 0.26 mm [femoral tunnel]; 1.58 +/- 0.75 vs 1.68 +/- 0.53 mm [tibial tunnel]). During stair descent, there was no difference in femoral or tibial tunnel motion between BTB and HS grafts at 6 weeks or 1 year. With running, there was no difference between graft types at 1 year. For all results, P values were > .05. Knee kinematics were consistent with the literature. CONCLUSION: During walking and stair descent, ACL reconstruction using suspensory fixation yielded no difference between graft types in femoral or tibial tunnel motion at 6 weeks or 1 year. All subjects were asymptomatic with knee kinematics similar to that of the literature. The significance of persistent, small (1 to 3 mm) movements at 1 year for healing or graft performance is unknown. CLINICAL RELEVANCE: These study results may have significant implications for graft choice, rehabilitation strategies, and timing for return to sports. PMID- 27411363 TI - Comparison of Videostroboscopy and High-speed Videoendoscopy in Evaluation of Supraglottic Phonation. AB - OBJECTIVES: To compare clinicians' ratings of videolaryngoscopy (VLS) and high speed videoendoscopy (HSV) and assess confidence of ratings with VLS and HSV in patients with supraglottic phonation. METHODS: The VLS and HSV video samples were taken from 11 adolescents post airway reconstruction who use supraglottic tissues for voice. The 22 recordings were randomized and presented to 4 clinicians: 2 speech-language pathologists and 2 pediatric otolaryngologists. Additionally, a 5 point Likert scale was used to rate level of confidence of ratings. RESULTS: Clinicians were more likely to rate regularity on HSV versus VLS videos (P = .003). Presence of mucosal wave was rated similarly on both imaging modalities; however, HSV was more likely to identify location (P = .002). Supraglottic phase symmetry (P = .014) and number of vibratory tissues used for phonation were rated more often with HSV versus VLS. Clinicians were more confident with HSV ratings compared to VLS ratings for determining vibration source, vibration pattern, and ability to make treatment decisions (P < .0001). CONCLUSIONS: The HSV improves the ability to rate tissue vibratory characteristics when compared with VLS in children with supraglottic phonation. This information may allow better understanding of the underlying mechanisms of voice production in these individuals, leading to improved therapeutic and surgical recommendations. PMID- 27411362 TI - Clinical Translation of Tissue Engineered Trachea Grafts. AB - OBJECTIVE: To provide a state-of-the-art review discussing recent achievements in tissue engineered tracheal reconstruction. DATA SOURCES AND REVIEW METHODS: A structured PubMed search of the current literature up to and including October 2015. Representative articles that discuss the translation of tissue engineered tracheal grafts (TETG) were reviewed. CONCLUSIONS: The integration of a biologically compatible support with autologous cells has resulted in successful regeneration of respiratory epithelium, cartilage, and vascularization with graft patency, although the optimal construct composition has yet to be defined. Segmental TETG constructs are more commonly complicated by stenosis and delayed epithelialization when compared to patch tracheoplasty. IMPLICATIONS FOR PRACTICE: The recent history of human TETG recipients represents revolutionary proof of principle studies in regenerative medicine. Application of TETG remains limited to a compassionate use basis; however, defining the mechanisms of cartilage formation, epithelialization, and refinement of in vivo regeneration will advance the translation of TETG from the bench to the bedside. PMID- 27411361 TI - Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function. AB - Aims: Cardiac resynchronization therapy (CRT) may exert its beneficial haemodynamic effect by improving ventricular synchrony and improving atrioventricular (AV) timing. The aim of this study was to establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronization. Methods and Results: We performed simulations using the CircAdapt haemodynamic model and performed haemodynamic measurements while adjusting AV delay, at low and high heart rates, in 87 patients with CRT devices. We assessed QRS duration, presence of fusion, and haemodynamic response. The simulations suggest that intrinsic PR interval and the magnitude of reduction in ventricular activation determine the relative importance of the mechanisms of benefit. For example, if PR interval is 201 ms and LV activation time is reduced by 25 ms (typical for current CRT methods), then AV delay optimization is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25 ms produced an additional 2.6 mmHg increase in blood pressure (30% of effect size observed with current CRT). In the clinical population, ventricular fusion significantly shortened QRS duration (Delta-27 +/- 23 ms, P < 0.001) and improved systolic blood pressure (mean 2.5 mmHg increase). Ventricular fusion was present in 69% of patients, yet in 40% of patients with fusion, shortening AV delay (to a delay where fusion was not present) produced the optimal haemodynamic response. Conclusions: Improving LV preloading by shortening AV delay is an important mechanism through which cardiac function is improved with CRT. There is substantial scope for further improvement if methods for delivering more efficient ventricular resynchronization can be developed. Clinical Trial Registration: Our clinical data were obtained from a subpopulation of the British Randomised Controlled Trial of AV and VV Optimisation (BRAVO), which is a registered clinical trial with unique identifier: NCT01258829, https://clinicaltrials.gov. PMID- 27411364 TI - Multiple eschars in scrub typhus: a case report. AB - Eschar in scrub typhus aids in early diagnosis and institution of appropriate therapy; however, the eschar positivity rates vary greatly in endemic regions. Multiple eschars in scrub typhus are a rare presentation. Our patient presented with fever and multiple eschars and was empirically started on doxycycline. Nested polymerase chain reaction from all the four eschars and from EDTA blood were positive for 56-kDa type-specific antigen which is specific for Orientia tsutsugamushi The patient recovered completely after 7 days of antibiotic treatment. He was from an area where scrub typhus was not observed previously. An eschar in an acute febrile patient from the "tsutsugamushi triangle" is a valuable sign in scrub typhus diagnosis. A search for multiple eschars in scrub typhus must be made by clinicians. PMID- 27411365 TI - Acute pancreatitis associated with scrub typhus. AB - Scrub typhus, or tsutsugamushi fever, is a zoonosis of rural Asia and the western Pacific islands. The causative organism, Orientia (formerly Rickettsia) tsutsugamushi, is transmitted to humans by the bite of a larval Leptotrombidium mite (chigger). Scrub typhus may have gastrointestinal presentations, such as acute acalculous cholecystitis, duodenal ulcer perforation, peritonitis and gastric ulceration. Acute pancreatitis with scrub typhus has been reported rarely. We report a patient of scrub typhus complicated by acute pancreatitis and acute kidney injury. PMID- 27411366 TI - Microtubule-independent secretion requires functional maturation of Golgi elements. AB - The Golgi complex is responsible for processing and sorting of secretory cargos. Microtubules are known to accelerate the transport of proteins from the endoplasmic reticulum (ER) to the Golgi complex and from the Golgi to the plasma membrane. However, whether post-Golgi transport strictly requires microtubules is still unclear. Using the retention using selective hooks (RUSH) system to synchronize the trafficking of cargos, we show that anterograde transport of tumor necrosis factor (TNF) is strongly reduced without microtubules. We show that two populations of Golgi elements co-exist in these cells. A centrally located and giantin-positive Golgi complex that sustains trafficking, and newly formed peripheral Golgi mini-stacks that accumulate cargos in cells without microtubules. Using a genome-edited GFP-giantin cell line, we observe that the trafficking-competent Golgi population corresponds to the pre-existing population that was present before removal of microtubules. All Golgi elements support trafficking after long-term depletion of microtubules and after relocation of Golgi proteins to the ER after treatment with Brefeldin A. Our results demonstrate that functional maturation of Golgi elements is needed to ensure post Golgi trafficking, and that microtubule-driven post-Golgi transport is not strictly required. PMID- 27411367 TI - The microtubule-severing protein fidgetin acts after dendrite injury to promote their degeneration. AB - After being severed from the cell body, axons initiate an active degeneration program known as Wallerian degeneration. Although dendrites also seem to have an active injury-induced degeneration program, no endogenous regulators of this process are known. Because microtubule disassembly has been proposed to play a role in both pruning and injury-induced degeneration, we used a Drosophila model to identify microtubule regulators involved in dendrite degeneration. We found that, when levels of fidgetin were reduced using mutant or RNA interference (RNAi) strategies, dendrite degeneration was delayed, but axon degeneration and dendrite pruning proceeded with normal timing. We explored two possible ways in which fidgetin could promote dendrite degeneration: (1) by acting constitutively to moderate microtubule stability in dendrites, or (2) by acting specifically after injury to disassemble microtubules. When comparing microtubule dynamics and stability in uninjured neurons with and without fidgetin, we could not find evidence that fidgetin regulated microtubule stability constitutively. However, we identified a fidgetin-dependent increase in microtubule dynamics in severed dendrites. We conclude that fidgetin acts after injury to promote disassembly of microtubules in dendrites severed from the cell body. PMID- 27411369 TI - High prevalence of adenomatous colorectal polyps in young cancer survivors treated with abdominal radiation therapy: results of a prospective trial. AB - OBJECTIVE: Cancer survivors treated with abdominal/pelvic radiation therapy (ART) have increased the risks of colorectal cancer (CRC), although evidence supporting early CRC screening for these patients is lacking. We sought to determine whether there is an elevated prevalence of adenomatous colorectal polyps in young survivors prior to the age when screening would be routinely recommended. DESIGN: We conducted a prospective study of early colonoscopic screening in cancer survivors aged 35-49 who had received ART >=10 years previously. The planned sample size was based on prior studies reporting a prevalence of adenomatous polyps of approximately 20% among the average-risk population >=50 years of age, in contrast to <=10% among those average-risk people aged 40-50 years, for whom screening is not routinely recommended. RESULTS: Colonoscopy was performed in 54 survivors, at a median age of 45 years (range 36-49) and after median interval from radiation treatment of 19 years (10.6-43.5). Forty-nine polyps were detected in 24 patients, with 15 patients (27.8%; 95% CI 17.6% to 40.9%) having potentially precancerous polyps. Fifty-three per cent of polyps were within or at the edge of the prior ART fields. CONCLUSIONS: Young survivors treated with ART have a polyp prevalence comparable with the average-risk population aged >=50 years and substantially higher than previously reported for the average-risk population aged 40-50 years. These findings lend support to the early initiation of screening in these survivors. CLINICAL TRIAL REGISTRATION NUMBER: NCT00982059; results. PMID- 27411370 TI - Chemical reactivity of graphene oxide towards amines elucidated by solid-state NMR. AB - Graphene oxide (GO) is an attractive nanomaterial for many applications. Controlling the functionalization of GO is essential for the design of graphene based conjugates with novel properties. But, the chemical composition of GO has not been fully elucidated yet. Due to the high reactivity of the oxygenated moieties, mainly epoxy, hydroxyl and carboxyl groups, several derivatization reactions may occur concomitantly. The reactivity of GO with amine derivatives has been exploited in the literature to design graphene-based conjugates, mainly through amidation. However, in this study we undoubtedly demonstrate using magic angle spinning (MAS) solid-state NMR that the reaction between GO and amine functions occurs via ring opening of the epoxides, and not by amidation. We also prove that there is a negligible amount of carboxylic acid groups in two GO samples obtained by a different synthesis process, hence eliminating the possibility of amidation reactions with amine derivatives. This work brings additional insights into the chemical reactivity of GO, which is fundamental to control its functionalization, and highlights the major role of MAS NMR spectroscopy for a comprehensive characterization of derivatized GO. PMID- 27411371 TI - Synthesis of Diverse Ag2O Crystals and Their Facet-Dependent Photocatalytic Activity Examination. AB - Sub- to micrometer-sized Ag2O cubes, great rhombicuboctahedra, cuboctahedra, corner-truncated octahedra, octahedra, and rhombic dodecahedra have been synthesized at room temperature using simple molar ratios of NH4NO3, NaOH, and AgNO3 solutions with a short reaction time. In addition, tuning the concentration of NH3 in the solution can provide more particle morphologies including edge- and corner-truncated cubes, small rhombicuboctahedra, and edge-truncated octahedra to enrich Ag2O shape diversity. X-ray photoelectron spectroscopy (XPS) spectra indicate surface composition of various crystals as pure Ag2O. Diffuse reflectance spectra have been used to determine the band gap of Ag2O cubes. Ag2O cubes, octahedra, and rhombic dodecahedra having the same total particle surface area were used for facet-dependent photocatalytic activity comparison in the degradation of methyl orange. Cubes are comparably highly active for this reaction, while octahedra and rhombic dodecahedra give moderate and low catalytic activities, respectively. Electron paramagnetic resonance (EPR) measurements confirm this reactivity order. Although all Ag2O samples show significant etching during photocatalysis, metallic silver is not produced. PMID- 27411368 TI - Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism. AB - OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. RESULTS: Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt-/- fibroblast cell lines and augmented epithelial intracellular bacterial killing. CONCLUSIONS: Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation. PMID- 27411372 TI - Influence of temperature, mixing, and addition of microcystin-LR on microcystin gene expression in Microcystis aeruginosa. AB - Cyanobacteria, such as the toxin producer Microcystis aeruginosa, are predicted to be favored by global warming both directly, through elevated water temperatures, and indirectly, through factors such as prolonged stratification of waterbodies. M. aeruginosa is able to produce the hepatotoxin microcystin, which causes great concern in freshwater management worldwide. However, little is known about the expression of microcystin synthesis genes in response to climate change related factors. In this study, a new RT-qPCR assay employing four reference genes (GAPDH, gltA, rpoC1, and rpoD) was developed to assess the expression of two target genes (the microcystin synthesis genes mcyB and mcyD). This assay was used to investigate changes in mcyB and mcyD expression in response to selected environmental factors associated with global warming. A 10 degrees C rise in temperature significantly increased mcyB expression, but not mcyD expression. Neither mixing nor the addition of microcystin-LR (10 MUg L-1 or 60 MUg L-1 ) significantly altered mcyB and mcyD expression. The expression levels of mcyB and mcyD were correlated but not identical. PMID- 27411374 TI - Erratum to: Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study. PMID- 27411373 TI - Determinants of stigma in a cohort of hellenic patients suffering from multiple sclerosis: a cross-sectional study. AB - BACKGROUND: Patients suffering from several neurologic disorders may bear the "stigma" of their disease, being disqualified from full social acceptance. Although stigma is considered to be present in Multiple Sclerosis (MS), the factors that influence its levels are ambiguous. Aim of our study was to examine, for the first time in the literature, the basic determinants of stigma in a Hellenic MS-patients cohort, as well as how stigma affects their Quality-of-Life (QoL) profiles. METHODS: Three hundred forty two patients were recruited in this study. Data collected concerned sociodemographic and disease-related variables, mental illness assessment, Multiple-Sclerosis-QoL-54 (MSQoL-54) and Stigma-Scale for-Chronic-Illness-24 (SSCI-24) questionnaires. Potential determinants were evaluated with univariate statistical analyses for their contribution to total, internalized (inner-self derived) and externalized (society derived) stigma. Important findings were further evaluated on hierarchical regression models. RESULTS: Disability levels were found to be the most powerful predictor in all stigma categories, followed by the presence of mental illness. Working and caregiving status were also ascertained as determinants of internalized stigma. Stigma levels displayed strong negative correlation with all composites of MSQoL 54. CONCLUSIONS: Stigma is present in the social environment of MS patients and was confirmed as a barrier (according to the International Classification of Functioning, Disability and Health), with detrimental effects on their QoL levels and functioning performances. Disability and mental illness were shown as the principal determinants of stigma, while financial characteristics were not as equally involved. Further validation of these results in other MS populations may provide safer conclusions, towards more efficacious patient-centered care outcomes. PMID- 27411376 TI - Family Interventions for Schizophrenia and the Psychoses: A Review. AB - Family psychoeducation as a treatment for schizophrenia was developed 40 years ago almost simultaneously and independently by investigators who at the time were not family therapists. Although the original goal was to decrease high expressed emotion as a means of preventing relapse, later variations have gone beyond to focus on social and role functioning and family well-being. Explicitly disavowing the earlier assumptions that family pathology caused relapse and deterioration, family psychoeducation seeks to engage family members as more sophisticated partners, complementing interventions by clinicians with specialized interactions and coping skills that counter the neurologic deficits inherent to the disorder. It has proved to be one of the most consistently effective treatments available. Reports on outcome studies now number more than 100, while meta-analyses put relapse rate reduction at 50-60% over treatment as usual. The most recent application in first episode and prodromal psychosis, combined with other evidence-based interventions, is yielding perhaps the most promising results yet achieved-substantial return of functioning and avoidance of psychosis altogether. Reviewed here are its scientific, theoretical, and clinical sources, a description of the most commonly applied version-the multifamily group format, selected clinical trials spanning those four decades, international and ethnic adaptations, and studies on mechanisms of efficacy. PMID- 27411375 TI - A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125. AB - The activity of RING ubiquitin ligases (E3s) depends on an interaction between the RING domain and ubiquitin conjugating enzymes (E2), but posttranslational events or additional structural elements, yet largely undefined, are frequently required to enhance or regulate activity. Here, we show for the ubiquitin ligase RNF125 that, in addition to the RING domain, a C2HC Zn finger (ZnF) is crucial for activity, and a short linker sequence (Li2(120-128)) enhances activity. The contribution of these regions was first shown with truncated proteins, and the essential role of the ZnF was confirmed with mutations at the Zn chelating Cys residues. Using NMR, we established that the C2HC ZnF/Li2(120-128) region is crucial for binding of the RING domain to the E2 UbcH5a. The partial X-ray structure of RNF125 revealed the presence of extensive intramolecular interactions between the RING and C2HC ZnF. A mutation at one of the contact residues in the C2HC ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Thus, we identified the structural basis for an essential role of the C2HC ZnF and conclude that this domain stabilizes the RING domain, and is therefore required for binding of RNF125 to an E2. PMID- 27411377 TI - Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures. AB - BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1.3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36.5 +/- 13.0 to 54.3 +/- 10.5 nmol L-1 (14.6 +/- 5.2 to 21.7 +/- 4.2 ng mL-1 ) in phototype II vs. 17.2 +/- 6.3 to 25.5 +/- 9.5 nmol L-1 (6.9 +/- 2.5 to 10.2 +/- 3.8 ng mL-1 ) in phototype V (P < 0.05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0.001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0.002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies. PMID- 27411378 TI - Prognostic and Clinicopathological Significance of Survivin Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. AB - Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically searched PubMed, Web of Science, and Embase to identify relevant studies until December 2015 and conducted a standard meta-analysis. Based on the inclusion and exclusion criteria, a total of 12 studies, including 2051 patients, were eligible for further analysis. Results showed that high survivin expression in RCC was associated with poor OS (HR = 2.84, 95% CI 1.68-4.79), CSS (HR = 2.36, 95% CI 1.41-3.95), and PFS (HR = 2.20, 95% CI 1.58-3.08). Survivin expression was also correlated with TNM stage (RR = 2.75, 95% CI 2.21-3.44), pathological T stage (RR = 2.19, 95% CI 1.75-2.75), lymph node metastasis (RR = 2.28, 95% CI 1.61-3.25), distant metastasis (RR = 1.56, 95% CI 1.16-2.08), Fuhrman grade (RR = 2.81, 95% CI 2.29-3.45), tumor size (RR = 1.49, 95% CI 1.24-1.78). Our study suggested that survivin was a prognostic marker in RCC. High survivin expression was correlated with poor prognosis and more advanced clinicopathological features, and it could serve as a biomarker for disease management. PMID- 27411379 TI - The type I interferon signature in leukocyte subsets from peripheral blood of patients with early arthritis: a major contribution by granulocytes. AB - BACKGROUND: The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. METHODS: Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). PBMCs were sorted into CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes by flow cytometry. Messenger RNA expression of three interferon response genes (IRGs RSAD2, IFI44L, and MX1) and type I interferon receptors (IFNAR1 and IFNAR2) was determined in whole blood and blood cell subsets by quantitative polymerase chain reaction. IRG expression was averaged to calculate an IFN score for each sample. RESULTS: Patients were designated "IFN(high)" (n = 8) or "IFN(low)" (n = 18) on the basis of an IFN score cutoff in whole peripheral blood from healthy control subjects. The difference in IFN score between IFN(high) and IFN(low) patients was remarkably large for the PMN fraction (mean 25-fold) compared with the other subsets (mean 6- to 9-fold), indicating that PMNs are the main inducers of IRGs. Moreover, the relative contribution of the PMN fraction to the whole-blood IFN score was threefold higher than expected from its abundance in blood (p = 0.008), whereas it was three- to sixfold lower for the other subsets (p <= 0.063), implying that the PMNs are most sensitive to IFN signaling. Concordantly, IFNAR1 and IFNAR2 were upregulated compared with healthy controls selectively in patient PMNs (p <= 0.0077) but not in PBMCs. CONCLUSIONS: PMNs are the main contributors to the whole-blood type I IFN signature in patients with early arthritis, which seems due to increased sensitivity of these cells to type I IFN signaling. Considering the well-established role of neutrophils in the pathology of arthritis, this suggests a role of type I IFN activity in the disease as well. PMID- 27411380 TI - Case report - calcification of the medial collateral ligament of the knee with simultaneous calcifying tendinitis of the rotator cuff. AB - BACKGROUND: Calcification of the medial collateral ligament (MCL) of the knee is a very rare disease. We report on a case of a patient with a calcifying lesion within the MCL and simultaneous calcifying tendinitis of the rotator cuff in both shoulders. CASE PRESENTATION: Calcification of the MCL was diagnosed both via x ray and magnetic resonance imaging (MRI) and was successfully treated surgically. Calcifying tendinitis of the rotator cuff was successfully treated applying conservative methods. CONCLUSION: This is the first case report of a patient suffering from both a calcifying lesion within the medial collateral ligament and calcifying tendinitis of the rotator cuff in both shoulders. Clinical symptoms, radio-morphological characteristics and macroscopic features were very similar and therefore it can be postulated that the underlying pathophysiology is the same in both diseases. Our experience suggests that magnetic resonance imaging and x-ray are invaluable tools for the diagnosis of this inflammatory calcifying disease of the ligament, and that surgical repair provides a good outcome if conservative treatment fails. It seems that calcification of the MCL is more likely to require surgery than calcifying tendinitis of the rotator cuff. However, the exact reason for this remains unclear to date. PMID- 27411381 TI - Nrf2-Mediated Neuroprotection Against Recurrent Hypoglycemia Is Insufficient to Prevent Cognitive Impairment in a Rodent Model of Type 1 Diabetes. AB - It remains uncertain whether recurrent nonsevere hypoglycemia (Hypo) results in long-term cognitive impairment in type 1 diabetes (T1D). This study tested the hypothesis that specifically in the T1D state, Hypo leads to cognitive impairment via a pathological response to oxidative stress. Wild-type (Control) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) null mice were studied. Eight groups of mice (Control and Nrf2(-/-) +/- T1D and +/- Hypo) were subject to recurrent, twice-weekly, insulin or saline injections over 4 weeks, after which cognitive function was assessed and brain tissue analyzed. Recurrent moderate hypoglycemia in T1D, but not Control, mice significantly impaired cognitive performance, and this was associated with hippocampal oxidative damage and inflammation despite an enhanced expression of Nrf2 and its target genes Hmox1 and Nqo1 In Nrf2(-/-) mice, both T1D and Hypo independently resulted in impaired cognitive performance, and this was associated with oxidative cell damage and marked inflammation. Together, these data suggest that Hypo induces an Nrf2 dependent antioxidant response in the hippocampus, which counteracts oxidative damage. However, in T1D, this neuroprotective mechanism is insufficient to prevent neuronal oxidative damage, resulting in chronic deficits in working and long-term memory. PMID- 27411382 TI - Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase. AB - MicroRNAs (miRNAs) have a fundamental role in diabetic heart failure. The cardioprotective miRNA-133a (miR-133a) is downregulated, and contractility is decreased in diabetic hearts. Norepinephrine (NE) is a key catecholamine that stimulates contractility by activating beta-adrenergic receptors (beta-AR). NE is synthesized from tyrosine by the rate-limiting enzyme, tyrosine hydroxylase (TH), and tyrosine is catabolized by tyrosine aminotransferase (TAT). However, the cross talk/link between TAT and TH in the heart is unclear. To determine whether miR-133a plays a role in the cross talk between TH and TAT and regulates contractility by influencing NE biosynthesis and/or beta-AR levels in diabetic hearts, Sprague-Dawley rats and miR-133a transgenic (miR-133aTg) mice were injected with streptozotocin to induce diabetes. The diabetic rats were then treated with miR-133a mimic or scrambled miRNA. Our results revealed that miR 133a mimic treatment improved the contractility of the diabetic rat's heart concomitant with upregulation of TH, cardiac NE, beta-AR, and downregulation of TAT and plasma levels of NE. In miR-133aTg mice, cardiac-specific miR-133a overexpression prevented upregulation of TAT and suppression of TH in the heart after streptozotocin was administered. Moreover, miR-133a overexpression in CATH.a neuronal cells suppressed TAT with concomitant upregulation of TH, whereas knockdown and overexpression of TAT demonstrated that TAT inhibited TH. Luciferase reporter assay confirmed that miR-133a targets TAT. In conclusion, miR 133a controls the contractility of diabetic hearts by targeting TAT, regulating NE biosynthesis, and consequently, beta-AR and cardiac function. PMID- 27411383 TI - Increased Skeletal Muscle GLUT4 Expression in Obese Mice After Voluntary Wheel Running Exercise Is Posttranscriptional. AB - Exercise promotes glucose clearance by increasing skeletal muscle GLUT4-mediated glucose uptake. Importantly, exercise upregulates muscle GLUT4 expression in an insulin-independent manner under conditions of insulin resistance, such as with type 2 diabetes. However, the insulin-independent mechanism responsible for rescued muscle GLUT4 expression is poorly understood. We used voluntary wheel running (VWR) in mice to test the prevailing hypothesis that insulin-independent upregulation of skeletal muscle GLUT4 protein expression with exercise is through increased Glut4 transcription. We demonstrate that 4 weeks of VWR exercise in obese mice rescued high-fat diet-induced decreased muscle GLUT4 protein and improved both fasting plasma insulin and hepatic triacylglyceride levels, but did not rescue muscle Glut4 mRNA. Persistent reduction in Glut4 mRNA suggests that a posttranscriptional mechanism regulated insulin-independent muscle GLUT4 protein expression in response to exercise in lean and obese mice. Reduction of GLUT4 protein in sedentary animals upon treatment with rapamycin revealed mTORC1 dependent GLUT4 regulation. However, no difference in GLUT4 protein expression was observed in VWR-exercised mice treated with either rapamycin or Torin 1, indicating that exercise-dependent regulation on GLUT4 was mTOR independent. The findings provide new insight into the mechanisms responsible for exercise dependent regulation of GLUT4 in muscle. PMID- 27411384 TI - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. AB - OBJECTIVES: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). METHODS: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. RESULTS: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p<0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. CONCLUSION: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel- HTPR in patients with carotid artery stenosis undergoing CEA. PMID- 27411385 TI - Multiple adaptive routes of Salmonella enterica Typhimurium to biocide and antibiotic exposure. AB - BACKGROUND: Biocides and antibiotics are used to eradicate or prevent the growth of microbial species on surfaces (occasionally on catheters), or infected sites, either in combination or sequentially, raising concerns about the development of co-resistance to both antimicrobial types. The effect of such compounds on Salmonella enterica, a major food-borne and zoonotic pathogen, has been analysed in different studies, but only few works evaluated its biological cost, and the overall effects at the genomic and transcriptomic levels associated with diverse phenotypes resulting from biocide exposure, which was the aim of this work. RESULTS: Exposure to triclosan, clorhexidine, benzalkonium, (but not to hypochlorite) resulted in mutants with different phenotypes to a wide range of antimicrobials even unrelated to the selective agent. Most biocide-resistant mutants showed increased susceptibility to compounds acting on the cell wall (beta-lactams) or the cell membranes (poly-L-lysine, polymyxin B, colistin or toxic anions). Mutations (SNPs) were found in three intergenic regions and nine genes, which have a role in energy production, amino acids, carbohydrates or lipids metabolism, some of them involved in membrane transport and pathogenicity. Comparative transcriptomics of biocide-resistant mutants showed over-expression of genes encoding efflux pumps (sugE), ribosomal and transcription-related proteins, cold-shock response (cpeE) and enzymes of microaerobic metabolism including those of the phosphotransferase system. Mainly ribosomal, metabolic and pathogenicity-related genes had affected expression in both in vitro-selected biocide mutants and field Salmonella isolates with reduced biocide susceptibility. CONCLUSIONS: Multiple pathways can be involved in the adaptation of Salmonella to biocides, mainly related with global stress, or involving metabolic and membrane alterations, and eventually causing "collateral sensitivity" to other antimicrobials. These changes might impact the bacterial environment interaction, imposing significant bacterial fitness costs which may reduce the chances of fixation and spread of biocide resistant mutants. PMID- 27411386 TI - Functional topography of the right inferior parietal lobule structured by anatomical connectivity profiles. AB - The nature of the relationship between structure and function is a fundamental question in neuroscience, especially at the macroscopic neuroimaging level. Although mounting studies have revealed that functional connectivity reflects structural connectivity, whether similar structural and functional connectivity patterns can reveal corresponding similarities in the structural and functional topography remains an open problem. In our current study, we used the right inferior parietal lobule (RIPL), which has been demonstrated to have similar anatomical and functional connectivity patterns at the subregional level, to directly test the hypothesis that similar structural and functional connectivity patterns can inform the corresponding topography of this area. In addition, since the association between the RIPL regions and particular functions and networks is still largely unknown, post-hoc functional characterizations and connectivity analyses were performed to identify the main functions and cortical networks in which each subregion participated. Anatomical and functional connectivity-based parcellations of the RIPL have consistently identified five subregions. Our functional characterization using meta-analysis-based behavioral and connectivity analyses revealed that the two anterior subregions (Cl1 and Cl2) primarily participate in interoception and execution, respectively; whereas the posterior subregion (Cl3) in the SMG primarily participates in attention and action inhibition. The two posterior subregions (Cl4, Cl5) in the AG were primarily involved in social cognition and spatial cognition, respectively. These results indicated that similar anatomical and functional connectivity patterns of the RIPL are reflected in corresponding structural and functional topographies. The identified cortical connectivity and functional characterization of each subregion may facilitate RIPL-related clinical research. Hum Brain Mapp 37:4316 4332, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27411388 TI - Mapping the protein-binding sites for iridium(iii)-based CO-releasing molecules. AB - A combination of mass spectrometry, Raman microspectroscopy, circular dichroism and X-ray crystallography has been used to obtain detailed information on the reaction of an iridium-based CO-releasing molecule (Ir-CORM), Cs2IrCl5CO, with a model protein, bovine pancreatic ribonuclease. The results show that Ir-compound fragments bind to the N-terminal amine and close to histidine and methionine side chains, and the CO ligand is retained for a long time. The data provide helpful information for identifying protein targets for Ir-CORMs and for studying the mechanism that allows them to exhibit their interesting biological properties. PMID- 27411389 TI - A follow-up study to assess the determinants and consequences of physical activity in pregnant women of Cuenca, Spain. AB - BACKGROUND: In recent years, the influence of physical exercise on pregnancy outcomes has been widely debated. Despite the numerous studies addressing the relationship between maternal physical activity and pregnancy outcomes, the evidence for consistent and significant impact of regular exercise during pregnancy on fetal growth remains lacking. The aims of this study were, first, to assess the level of physical activity performed throughout the pregnancy by objective (accelerometer) and self-reported (questionnaire) measurements, and, second, to ascertain pre-pregnancy physical activity levels, to estimate the relationship between levels of physical activity and some pregnancy and neonatal outcomes. METHODS/DESIGN: This was a prospective cohort study. Participants were pregnant women (n = 194) aged 18 to 40 years who attended for three quarterly appointments for pregnancy ultrasound scans at the Virgen de la Luz Hospital in Cuenca, Spain. All participants provided written informed consents to participate in the study. Physical activity during the pregnancy follow-up was assessed by a self-reported Pregnancy Physical Activity Questionnaire and sleep log; also objectively by a GT3X accelerometer (ActiGraph). Furthermore, pregnancy symptoms inventory, nutritional behavioural assessment, socio-demographic characteristics, and anthropometry and body composition were measured. At the end of the follow up, the following main outcomes were determined: pregnancy outcomes (incidence of gestational diabetes mellitus, pre-eclampsia, pregnancy-induced hypertension, weight gain during pregnancy, type of delivery, and neonatal outcomes (gestational age, birth weight, gender, Apgar score 1 min/5 min, type of resuscitation (I/II/III/IV), and pH of umbilical cord blood). Descriptive statistics for cross-sectional data, linear mixed regression models for absolute differences in changes baseline-final measurements were used as statistical analyses. DISCUSSION: Although the effectiveness of physical activity programmes on improving maternal and neonatal outcomes has heretofore been studied, the impact of free time physical activity during pregnancy has not been assessed using objective measures. This paper reports the design of a prospective cohort study that aims to assess the physical activity levels of pregnant women, and to estimate the relationship between those physical activity levels with maternal and neonatal outcomes. This study could contribute to providing evidence for the formulation of recommendations for physical activity for pregnant women. PMID- 27411387 TI - 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells. AB - BACKGROUND: Endocannabinoids have recently drawn attention as promising anti cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. METHODS AND RESULTS: DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5 lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. CONCLUSIONS: From these findings, we suggest that ROS production induced by the 5 LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it. PMID- 27411390 TI - Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor. AB - BACKGROUND: The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination of in vivo and ex vivo models together with ECM remodeling markers may provide a translational tool for screening of potential treatments for IPF. METHODS: Twenty female Sprague Dawley rats, twelve weeks of age, were administrated either two doses of bleomycin (BLM) (n = 14) or saline (n = 6) I.T., two days apart. Ten rats were euthanized at day seven and the remaining ten rats at day fourteen, after the last dose. Precision-cut lung slices (PCLS) were made and cultured for 48 h. Ten female Sprague-Dawley rats, twelve weeks of age, were administrated either two doses of BLM (n = 7) or saline (n = 3) I.T., two days apart. The rats were euthanized fourteen days after the last dose. PCLS were made and cultured for 48 h in: medium, medium + 100 MUM IBMX (PDE inhibitor), or medium + 10 MUM GM6001 (MMP inhibitor). Turnover of type I collagen (P1NP, C1M), type III collagen (iP3NP, C3M) and elastin degradation (ELM7) was measured in the supernatant of the cultured PCLS. RESULTS: P1NP, C1M, iP3NP, C3M and ELM7 were significantly increased in supernatants from BLM animals (P <= 0.05 - P <= 0.0001) when compared to controls. P1NP, C1M, iP3NP, C3M and ELM7 were significantly increased in supernatants from day seven BLM animals compared to day fourteen BLM animals (P <= 0.05 - P <= 0.0001). P1NP, C1M, iP3NP, C3M and ELM7 were significantly decreased when adding IBMX to the culture medium of fibrotic lung tissue (P <= 0.05 - P <= 0.0001). C1M, C3M and ELM7 were significantly decreased when adding GM6001 to the culture medium (P <= 0.05 - P <= 0.0001). Sirius Red and Orcein staining confirmed the presence of collagen and elastin deposition in the lungs of the animals receiving BLM. CONCLUSIONS: The protein fingerprint technology allows the assessment of ECM remodeling markers in the BLM PCLS model. By combining in vivo, ex vivo models and the protein fingerprint technology in the fibrotic phase of the model, we believe the chance of translation from animal model to human is markedly increased. PMID- 27411391 TI - OsPAP10c, a novel secreted acid phosphatase in rice, plays an important role in the utilization of external organic phosphorus. AB - Under phosphate (Pi ) starvation, plants increase the secretion of purple acid phosphatases (PAPs) into the rhizosphere to scavenge organic phosphorus (P) for plant use. To date, only a few members of the PAP family have been characterized in crops. In this study, we identified a novel secreted PAP in rice, OsPAP10c, and investigated its role in the utilization of external organic P. OsPAP10c belongs to a monocotyledon-specific subclass of Ia group PAPs and is specifically expressed in the epidermis/exodermis cell layers of roots. Both the transcript and protein levels of OsPAP10c are strongly induced by Pi starvation. OsPAP10c overexpression increased acid phosphatase (APase) activity by more than 10-fold in the culture media and almost fivefold in both roots and leaves under Pi sufficient and Pi -deficient conditions. This increase in APase activity further improved the plant utilization efficiency of external organic P. Moreover, several APase isoforms corresponding to OsPAP10c were identified using in-gel activity assays. Under field conditions with three different Pi supply levels, OsPAP10c-overexpressing plants had significantly higher tiller numbers and shorter plant heights. This study indicates that OsPAP10c encodes a novel secreted APase that plays an important role in the utilization of external organic P in rice. PMID- 27411392 TI - Stimulation of Tumor-Specific Immunity by p5 HER-2/neu Generated Peptide Encapsulated in Nano-liposomes with High Phase Transition Temperature Phospholipids. AB - BACKGROUND: The aim of this study is to evaluate the possible advantages of liposomes with high transition temperature (Tm) in the function of a vaccine for P5 HER2/neu-generated peptide and its adjuvant action to elicit CD8+ T cell response and its efficacy in TUBO in vivo tumor mice model, which over expresses the HER2/neu oncogene. P5, a hydrophobic peptide, was encapsulated in the nanoliposomes consisting of DSPC/DSPG/Chol(Tm 54 degrees C) with a chaotropic loading system via 7M urea and described by size, zeta potential, encapsulation efficiency, and the structural stability of SDS-PAGE. METHODS: We immunized the mice for three times subcutaneously based on a two-week intervals using encapsulated peptide in the nanoliposomes, empty liposome, P5 in PBS, and PBS. Enzyme-linked immunospot assay, cytotoxicity test, and flow cytometric studies followed by the size of tumor and survival time measurements, which were done in TUBO tumor mice version. RESULTS: Findings of ELISpot and flow cytometric analysis showed that immunization with Lip-p5 nanoliposomes has enhanced the antigen-specific IFN-gamma response of CD8+ T cells and induced CTL response, which resulted in a smaller tumor and longer survival time. In addition to increase in amounts of IFN-gamma-CD8+ T cells in a group, which was immunized with Lip-P5, our findings also revealed a Th1 shift in the group immunized with an empty liposome with reduced frequencies of IL-4-producing cells and increase of IFN-gamma-producing cells. CONCLUSION: The results indicated that simple liposomes consisting of phospholipids with high transition temperature could be an effective vaccine vehicle for tumor-associated antigens for inducing cell mediate immunity. PMID- 27411393 TI - Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease. AB - BACKGROUND: Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved. METHODS: Male Sprague-Dawley rats (SD) were intraperitoneally injected with THP (0.3 and 1.0 mg/kg) or normal saline (NS) for 7 months. Alterations in cognitive and behavioral performance were assessed using the Morris water maze (MWM) and open field tests. After behavior tests, whole genome oligo microarrays, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence-confocal were used to investigate the global mechanisms underlying THP-induced neuropathology with aging. RESULTS: Compared with NS controls, the MWM test results showed that THP-treated rats exhibited significantly extended mean latencies during the initial 3 months of testing; however, this behavioral deficit was restored between the fourth and sixth month of MWM testing. The same tendencies were confirmed by MWM probe and open field tests. Gene microarray analysis identified 68 (47 %) upregulated and 176 (53 %) downregulated genes in the "THP-aging" vs. "NS-aging" group. The most significant populations of genes downregulated by THP were the immune response-, antigen processing and presentation-, and major histocompatibility complex (MHC)-related genes, as validated by qRT-PCR. The decreased expression of MHC class I in THP treated aging brains was confirmed by confocal analysis. Notably, long-term THP treatment primed hippocampal and cortical microglia to undergo an inflammatory phenotypic switch, causing microgliosis and microglia activation, which were positively accompanied by pathological misfolded tau lesions. CONCLUSIONS: Our findings suggest that immune response and neuroinflammation represent a pivotal mechanism in THP-induced AD-like neuropathology processes with long-term exposure to AC drugs. PMID- 27411395 TI - Correction to: "Human Chorionic Gonadotropin Modulates Prostate Cancer Cell Survival after Irradiation or HMG CoA Reductase Inhibitor Treatment". PMID- 27411396 TI - Endoscopic ultrasound-guided transoral drainage of parapharyngeal abscess. PMID- 27411394 TI - Shared genetic variants between serum levels of high-density lipoprotein cholesterol and wheezing in a cohort of children from Cyprus. AB - BACKGROUND: In a cohort of children in Cyprus, we recently reported low levels of high density lipoprotein cholesterol (HDL-C) to be associated with asthma. We examined whether genetic polymorphisms that were previously linked individually to asthma, obesity, or HDL-C are associated with both asthma and HDL-C levels in the Cyprus cohort. METHODS: We assessed genotypes frequencies in current-wheezers (n = 190) and non-asthmatic controls (n = 671) and HDL-C levels across several genotypes. Binary logistic regression models were used to assess the effect of genotypes on wheezing risk and examined whether this effect is carried out through changes of HDL-C. RESULTS: Of the 16 polymorphisms tested, two polymorphisms TNFa rs3093664 and PRKCA rs9892651 presented significant differences in genotype distribution among current-wheezers and controls. Higher HDL-C levels were noted in carriers of genotype GG of polymorphism TNFa rs3093664 that was protective for wheezing Vs AG and AA genotypes (65.3 Vs 51.8 and 53.3 mg/dl, p-value < 0.001 and p-value for trend = 0.028). In polymorphism PRKCA rs9892651, HDL-C levels were lower in carriers of CC and TC genotypes that were more frequent in current-wheezers Vs TT genotype (52.2 and 52.7 Vs 55.2 mg/dl, p value = 0.042 and p-value for trend = 0.02). The association of TNFa rs3093664 with wheezing is partly mediated by its effect on HDL-C whereas association of PRKCA rs9892651 with wheezing appeared to be independent of HDL-C. CONCLUSIONS: We found evidence that two SNPs located in different genetic loci, are associated with both wheezing and HDL-C levels, although more studies in other populations are needed to confirm our results. PMID- 27411397 TI - Effect of cobalt doping on the structural, magnetic and abnormal thermal expansion properties of NaZn13-type La(Fe1-xCox)11.4Al1.6 compounds. AB - Cubic NaZn13-type La(Fe1-xCox)11.4Al1.6 compounds were synthesized and extensively explored through crystal structure and magnetization analyses. By optimizing the chemical composition, the isotropic abnormal properties of excellent zero and giant negative thermal expansion in a pure form were both found at different temperature ranges through room temperature. Moreover, the temperature regions with the remarkable abnormal thermal expansion (ATE) properties have been broadened which are controlled by the dM/dT. The present study demonstrates that the ATE behavior mainly depends on special structural and magnetic properties. These diverse properties suggest the high potential of La(Fe1-xCox)11.4Al1.6 for the development of abnormal expansion materials. PMID- 27411400 TI - Genetics: Postmortem genetic testing uncovers causes of SCD in young individuals. PMID- 27411398 TI - AP-1/sigma1A and AP-1/sigma1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway. AB - The sigma1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express sigma1A and one of the sigma1B and sigma1C isoforms. Brain is the tissue with the highest sigma1A and sigma1B expression. sigma1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/sigma1A and AP-1/sigma1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway. sigma1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5. AP-1/sigma1A ArfGAP1-Rabex-5 complex formation leads to more endosomal Rabex-5 and enhanced, Rab5(GTP)-stimulated Vps34 PI3-kinase activity, which is essential for multivesicular body endosome formation. Formation of AP-1/sigma1A-ArfGAP1-Rabex-5 complexes is prevented by sigma1B binding of Rabex-5 and the amount of endosomal Rabex-5 is reduced. AP-1 complexes differentially regulate endosome maturation and coordinate protein recycling and degradation, revealing a novel molecular mechanism by which they regulate protein transport besides their established function in clathrin-coated-vesicle formation. PMID- 27411399 TI - Syncope: Drug shows promise for vasovagal syncope. PMID- 27411401 TI - Diabetes: Time for reconciliation between cardiologists and diabetologists. PMID- 27411402 TI - Psychosocial and psychoneuroendocrinal aspects of Takotsubo syndrome. AB - Great advances have been made in our understanding of Takotsubo syndrome in the past decade, but the aetiology of the condition remains incompletely understood. The most established theory, that catecholamine-mediated myocardial stunning is provoked by emotional or physiological stress, is supported by the presence of supraphysiological levels of plasma catecholamines in patients with Takotsubo syndrome. For this reason, the hyperexcitability of the autonomic nervous system under conditions of physical and emotional stress is often assessed in these patients. Observational studies have indicated that a predisposing influence of chronic or traumatic stress, anxiodepressive disorders, and maladaptive personality traits are linked to the pathogenesis of Takotsubo syndrome. Chronic stress can influence autonomic function through dysregulation of the hypothalamic pituitary-adrenal axis and contribute to the development of cardiovascular disorders. In this Perspectives article, we discuss the current knowledge of the psychoneuroendocrinological and psychosocial mechanisms underlying the pathophysiology of Takotsubo syndrome. PMID- 27411404 TI - Extending Time Profile of Morphine-Induced Analgesia Using a Chitosan-Based Molecular Imprinted Polymer Nanogel. AB - Chitosan-based molecular imprinted polymer (CS-MIP) nanogel is prepared in the presence of morphine template, fully characterized and used as a new vehicle to extend duration of morphine analgesic effect in Naval Medical Research Institute mice. The CS-MIP nanogel with ~25 nm size range exhibits 98% loading efficiency, and in vitro release studies show an initial burst followed by an extended slow release of morphine. In order to study the feasibility of CS-MIP nanogel as morphine carrier, 20 mice are divided into two groups randomly and received subcutaneous injection of morphine-loaded CS-MIP and morphine (10 mg kg-1 ) dissolved in physiologic saline. Those received injection of morphine-loaded CS MIP show slower and long lasting release of morphine with 193 min effective time of 50% (ET50) analgesia compared to 120 min ET50 in mice received morphine dissolved in physiologic saline. These results suggest that CS-MIP nanogel can be a possible strategy as morphine carrier for controlled release and extension of its analgesic efficacy. PMID- 27411406 TI - The organocatalytic ring-opening polymerization of N-tosyl aziridines by an N heterocyclic carbene. AB - The ring-opening polymerization of N-tosyl aziridines, in the presence of 1,3 bis(isopropyl)-4,5(dimethyl)imidazol-2-ylidene as an organocatalyst and an N tosyl secondary amine as initiator mimicking the growing chain, provides the first metal-free route to well defined poly(aziridine)s (PAz) and related PAz based block copolymers. PMID- 27411405 TI - Corneal deposits secondary to rifabutin. PMID- 27411403 TI - Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy. AB - Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' - a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed. PMID- 27411407 TI - The risk of venous thromboembolism in patients with hepatitis C. A systematic review and meta-analysis. AB - Some studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Unfortunately, available data on this association are contrasting. A systematic review and meta-analysis of literature studies was performed to evaluate the risk of venous thromboembolism (VTE) associated with HCV. Studies reporting on VTE risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Six studies (10 data-sets) showed a significantly increased VTE risk in 100,364 HCV patients as compared with 8,471,176 uninfected controls (odds ratio [OR]: 1.900; 95 % confidence interval [CI]: 1.406, 2.570; p<0.0001). These results were confirmed when specifically considering the risk of DVT (6 studies, OR: 1.918; 95 %CI: 1.351, 2.723; p<0.0001), whereas a trend towards an increased risk of PE was documented in HCV patients (4 studies, OR: 1.811; 95 %CI: 0.895, 3.663; p=0.099). The increased VTE risk associated with HCV infection was consistently confirmed when analysing four studies reporting adjusted risk estimates (OR: 1.876; 95 %CI: 1.326, 2.654; P<0.0001), and after excluding studies specifically enrolling populations exposed to transient risk factors for VTE (4 studies, OR: 1.493; 95 %CI: 1.167, 1.910; p=0.001). Meta-regression models suggested that age and male gender may significantly impact on the risk of VTE associated with HCV-positivity. Results of our meta-analysis suggest that HCV-infected subjects may exhibit an increased risk of VTE. However, further high quality studies are needed to extend and confirm our findings. PMID- 27411409 TI - Pediatric Tuberculosis in Turkey: A Review of 8-Years Period in a Tertiary Care Hospital. AB - The purpose of this study was to evaluate the clinical, radiological, microbiological characteristics, side effects of anti-TB drugs and treatment outcome of childhood definite or probable TB. The medical records of all childhood TB patients were investigated in the department of pediatric infectious disease of a tertiary care hospital between January 2005 and December 2012. Patients who followed-up until the anti-TB treatment was completed were included in the study. One hundred forty four pediatric cases with active TB were included in the study (27 definite, 117 probable). Twenty-four (16.7 %) patients were asymptomatic at admission. Pulmonary TB was the most common type. The most common localizations for extrapulmonary TB were superficial lymphadenitis. An index case was detected in 39.6% of the patients. In conclusion, the absence of constitutional symptoms does not exclude TB. Household contact screening plays an important role in the diagnosis of childhood TB especially in asymptomatic patients. PMID- 27411408 TI - In myotonic dystrophy type 1 reduced FDG-uptake on FDG-PET is most severe in Brodmann area 8. AB - BACKGROUND: In myotonic dystrophy type 1 (DM1), only one FDG-PET study used statistical parametric mapping (SPM) showing frontal reduced FDG-uptake. Our aim was to 1) identify the FDG-PET area with the most severe reduced FDG-uptake using SPM8 in a larger group of patients 2) assess potential correlation between CTG numbers and FDG-PET. METHODS: FDG-PET was performed in 24 patients and compared to 24 controls. Pearson's correlation was used to analyse correlation. RESULTS: SPM8 revealed Brodmann area 8 as the area with the most severe reduced FDG uptake. Weak, although not statistically significant, correlation was observed between CTG-numbers and reduced FDG-uptake in Brodmann area 8. CONCLUSION: In DM1, Brodmann area 8 is the area with the most severe reduced FDG-uptake on FDG PET. Brodmann area 8 reduced FDG-uptake is correlated -although weakly- to CTG repeat numbers. PMID- 27411410 TI - Childhood Epilepsy with Occipital Paroxysm: Classification, Atypical Evolution and Long-Term Prognosis in 35 Patients. AB - We studied childhood epilepsy with occipital paroxysms (CEOP) with regard to typical and/or atypical ictal symptoms, EEG findings, as well as atypical evolution and outcome. This report focuses on the main clinical and EEG features of CEOP underlying its atypical symptoms and its management. Thirty-five patients with CEOP were subdivided into Panayiotopoulos syndrome (n=15), Gastaut syndrome (n=11), and mixed type (n=9). Nine patients (25%) with CEOP (mixed type) had shown atypical ictal manifestations and presented combinations of vomiting (100%) along with visual symptoms (66%), and/or eye deviation (66%), and headaches (44%). Five patients with CEOP had atypical evolution. However, the dictate for strict delineation into either the early-onset or late-onset forms of CEOP should be discarded because many children will present mixed clinical findings at varying ages. We think a detailed evaluation should be carried out as to why certain patients who apply have atypical findings, and whether each patient has age related evolution or not. PMID- 27411411 TI - Bonzai Intoxication in Children: Our Experience with 17 Cases. AB - Synthetic cannabinoid receptor agonists are becoming increasingly popular in adolescent age group as an abused substance. Therefore, pediatric emergency physicians should be prepared for Bonzai utilizations which are being more common day by day. The aim of the study is to investigate cases who admitted to a pediatric emergency service with use of Bonzai. PMID- 27411412 TI - Clinical features and treatment results in children with anaplastic large cell lymphoma. AB - Anaplastic large cell lymphoma (ALCL) tends to have frequent relapse and good response to salvage chemotherapy. The frequency of ALCL among 1486 Non-Hodgkin's lymphoma (NHL) cases followed-up since 1972 was 1.5%, however, the percentage was 9.3% in cases diagnosed after 2000. Event-free survival (EFS) and overall survival (OS) rates for 23 children were 32.2% and 72.8% at 3 years, respectively. Disseminated diseases, no response to first line treatment, anaplastic lymphoma kinase (ALK) negativity were found as significant predictors on survival of ALCL. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with ALK negative status should be monitored carefully because of the poor prognostic factors, and treated differently. The survival rates in this study are need of further improvement since the survival rates with current protocols are achievable at a level more than 80%. This is mainly related with late referral of those children with advanced disease. PMID- 27411413 TI - Development of a screening tool for children's growing pains: validation, reliability control and clinical evaluation. AB - Growing pains (GP) is the most common musculoskeletal complaint in childhood. The present study describes the development, validation and clinical evaluation of a questionnaire for the detection of GP in the general children's population aged 4 -7 years of age. Based on the existing publications, a 27-point closed type questionnaire was developed and was administered to a parental population of school-age children for standardization. Nine questions evaluating pain localization, intensity and 24-hour temporal distribution, exhibited excellent validity and reliability and were finally selected. A cut-off point of ? 8 was proposed for GP's diagnosis. Questionnaire's sensitivity and specificity were studied in a sample of outpatient children attending an orthopedic clinic for lower limb pain of no apparent traumatic origin. The diagnosis of GP based on the questionnaire coincided with the orthopedic diagnosis in all cases. The proposed questionnaire is a reliable and valid screening tool for GP. PMID- 27411414 TI - The perceptions of pediatricians regarding their self-efficacy in child neglect and abuse. AB - Child abuse is one of the most severe forms of childhood trauma which has pervasive and long-lasting effects on children, their families, and the society. These effects, impairing the development of the victims, extend far beyond childhood into adolescence and adulthood. Pediatricians are the most common group of clinicians who encounter abused children immediately. Therefore, it is important for a pediatrician to be aware of the symptoms of abuse and neglect, and to feel sufficient about reporting in order to release and prevent the trauma. We aimed to assess awareness and self-efficacy about recognizing, diagnosing and reporting. Pediatricians completed the questionnaire created by the researchers. There were differences about pediatricians' perception of self efficacy and approach to abuse. Pediatricians experience difficulties about the diagnosis of child abuse and neglect through the process from examination to reporting. PMID- 27411415 TI - Empiric treatment of children with gastroesophageal reflux-like symptoms: Effect of proton pump inhibitors. AB - Gastroesophageal reflux disease is an important cause of morbidity in childhood. Although various diagnostic methods are available, short course of empiric treatment with a proton pump inhibitor is widely used in adults as a diagnostic test. Data about empiric treatment is scarce in children. The aim of this study is to evaluate the effectiveness of empiric treatment of reflux-like symptoms in children. Pediatric gastroenterology outpatient files were searched and patients with a diagnosis of gastroesophageal reflux were found. Patient complaints, history and the treatments provided were recorded. Treatment naive patients older than 2 years of age with symptoms suggestive of gastroesophageal reflux were selected and included if they were given empiric treatment with a proton pump inhibitor. Empiric treatment was found to be effective in 78% of patients. Treatment response tended to be better in children older than 5 years of age. Of the 22 non-responders 9 underwent endoscopy and pathological findings were discovered in 7 of them. Treatment of children with gastroesophageal reflux symptoms with a proton pump inhibitor might significantly decrease the need for extensive evaluations. However it is important to investigate non-responders to empiric therapy, as it seems there might be high probability of pathological findings. PMID- 27411416 TI - Prolonged pacifier usage in infancy does not cause eating behavior problem later. AB - The objective of this study conducted in children aged 3-7 years was to determine whether pacifier use during infancy is associated with eating problems in later periods. A total of 85 children (55.2 +/-12.3 months) admitted to hospital with eating problems and with no organic pathology in scans, and 97 healthy children (52.24+/-10.97 months) without eating problems, were assigned to case and control groups, respectively. Eating problems were classified into five groups and investigated via a questionnaire. The presence of eating problems was analyzed for association with pacifier use. There was no significant difference between the two groups in terms of pacifier use (chi-square test: 0.141, p=0.707), and pacifier use is not related to a poor appetite in later periods. Pediatric healthcare providers and parents should be informed with regard to the subject. PMID- 27411417 TI - Aspartate aminotransferase-to-platelet ratio index in children with cholestatic liver diseases to assess liver fibrosis. AB - To assess the relationship between aspartate aminotransferase-platelet ratio index (APRI) and liver fibrosis in children with chronic hepatocellular and biliary cholestatic liver diseases. A retrospective review of one hundred children's demographic and laboratory findings concurrent with liver biopsy, who were followed-up with prolonged cholestasis. The diagnostic accuracy of the APRI was assessed by receiver operating characteristic (ROC) curves. Advanced fibrosis was more common in the hepatocellular group. The APRI values of the two groups were similar. The patients with advanced fibrosis had significantly higher APRI values than patients with mild fibrosis, in both the hepatocellular and biliary groups. The areas under the ROC were 0.68 and 0.81 in the hepatocellular and biliary groups respectively. The cut-off values of APRI for discriminating advanced fibrosis were 0.93 (65% sensitivity, 69% specificity) in the hepatocellular group and 2.35 (62% sensitivity, 96% specificity) in the biliary group. APRI may be most efficient for discriminating between advanced and mild fibrosis in biliary cholestatic liver disease patients. PMID- 27411418 TI - Total oxidant status, total antioxidant capacity and ischemia modified albumin levels in children with celiac disease. AB - In our study, we aimed to investigate ischemia modified albumin (IMA) as an oxidative stress marker, as well as other oxidant and antioxidant markers that have not been evaluated in children with celiac disease. A total of 37 pediatric patients who were diagnosed with celiac disease (CD) and 29 healthy children were enrolled in this prospective study. We evaluated the IMA, total oxidant status, total antioxidant capacity, sulfhydryl, and advanced oxidation protein products in all of the subjects. We also compared the levels at the time of the diagnosis, and following a gluten-free diet (GFD) in the children with CD. While the IMA and the other oxidant marker levels were significantly higher in the patient group compared to the control group, the antioxidant marker levels were found to be significantly lower in the patient group, compared to the control group. We also determined that the tissue transglutaminase IgA showed a highly positive correlation, and that the IMA showed a moderately positive correlation with the Marsh-Oberhuber histopathological stage. Additionally, the IMA and other oxidant marker levels were significantly lower, while the antioxidant marker levels were significantly higher after the GFD, compared to the pre-diet period. We detected that oxidative stress played a role in the pathogenesis of CD, and that this could be evaluated using oxidative stress markers, which would regress after the GFD. We also detected that IMA is a marker that shows a correlation with the histopathological stage, and may be used in the diagnosis. PMID- 27411419 TI - Clinical and neuroradiologic variability of Aicardi-Goutieres syndrome: Two siblings with RNASEH2C mutation and a boy with TREX1 mutation. AB - Aicardi-Goutieres syndrome (AGS) is a rare, autosomal recessively inherited, immune-mediated neurodevelopmental disorder. The syndrome causes infantile-onset progressive encephalopathy characterized by the neuroradiologic features of basal ganglia and periventricular white matter calcification, leucodystrophy and cerebral atrophy. Lymphocytosis and elevated levels of interferon alpha (IFN alpha) in the cerebrospinal fluid are supplementary findings of AGS. It is frequently misdiagnosed as sequelae of congenital infection (pseudo-TORCH) and mostly recognized later. We describe three AGS cases with different clinical presentation, two male siblings with RNASEH2C mutation and a boy with TREX1 mutation. These cases highlight the importance of considering AGS in the differential diagnosis of unexplained leukoencephalopathy and developmental delay. We suggest to search for intracranial calcification, especially if there are more than one affected cases in a family. PMID- 27411421 TI - A case of hyperkinetic movement disorder associated with LGI1 antibodies. AB - Encephalitis associated with leucine-rich glioma inactivated 1 (LGI1) antibodies is often encountered in elderly male patients and may infrequently present with isolated syndromes. A 6-year-old boy was admitted with acute onset severe oral and facial stereotypic and choreiform movements. On his neurologic examination, he had repetitive and rhythmic movements in orolingual muscles including tongue protrusion, limb chorea and minimal facial stereotypic movements. Anti streptolysin O (ASO) titers were found severely elevated in several measurements. Well-characterized antibodies against ion channels and synapse proteins were negative whereas LGI1 antibody was positive in both serum and CSF. Marked clinical improvement was observed after immunotherapy. Here, we present the first pediatric case with LGI1 antibody associated hyperkinetic movement disorders and emphasize the importance of investigating neuronal autoantibodies in patients with isolated and treatment resistant movement disorders. PMID- 27411420 TI - Importance of neurologic and cutaneous signs in the diagnosis of Schimke immuno osseous dysplasia. AB - Schimke immuno-osseous dysplasia is an autosomal recessive multisystem disorder caused by defects in SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 gene (SMARCAL1). SMARCAL1 product is a helicase that has role in selective cellular proliferation. The disorder is characterized by spondyloepiphyseal dysplasia with short stature, nephropathy, T cell deficiency, neurologic and cutaneous signs. Patients may have hyperpigmented skin lesions similar to cafe au lait spots. Symptoms and disease severity in Schimke immuno-osseous dysplasia varies from patient to patient. Genetic, epigenetic and environmental factors play role on the severity of the disease. Here we report on a patient with short stature, steroid resistant nephrotic syndrome and recurrent infections. Cutaneous findings and developmental delay helped us to reach the diagnosis of Schimke immuno-osseous dysplasia. A homozygous missense mutation in SMARCAL1 gene confirmed the clinical diagnosis. PMID- 27411422 TI - Systemic onset juvenile idiopathic arthritis with macrophage activation syndrome and coronary artery dilatation misdiagnosed as Kawasaki disease. AB - Systemic onset juvenile idiopathic arthritis (SoJIA) is characterized by arthritis, fever and visceral organ involvement including hepatosplenomegaly, lympadenopathy and serositis. This is a case of SoJIA misdiagnosed as Kawasaki disease (KD) and developed machrophage activation syndrome (MAS) secondary to Ebstein-Barr virus (EBV) infection. It is presented to point out the conditions that may come along. First of all, SoJIA should be kept in mind while making the differential diagnosis of coronary arterial ectasias and dilatations usually seen in vasculitic diseases like KD. Second, as a very fatal complication MAS should always be considered while following a patient with the diagnosis of SoJIA. Infections like EBV may be the potential triggers for development of MAS especially in immunesupressed patients. PMID- 27411423 TI - A Presentation of Lyme Disease: Pseudotumor Cerebri. AB - Lyme disease is caused by a tick-transmitted spirochete, B. burgdorferi. It can present with both central and peripheral nervous system manifestations, including aseptic meningitis, meningoencephalitis, Bell's palsy and other cranial neuropathies, radiculoneuritis, and myelitis. However, pseudotumor cerebri associated with Lyme disease is rare. Here, we report a eight-year-old girl with the unusual manifestation of pseudotumor cerebri associated Lyme disease. PMID- 27411424 TI - A Rare Hydrocephalus Complication: Cortical Blindness. AB - Cortical blindness related to bilateral occipital lobe infarction is an extremely rare complication of hydrocephalus. Compression of the posterior cerebral artery, secondary to tentorial herniation, is the cause of occipital infarction. Particularly in children and mentally ill patients, cortical blindness may be missed. Therefore, early diagnosis and treatment of hydrocephalus is important. We present herein a child of ventricular shunt malfunction complicated by cortical blindness. PMID- 27411425 TI - Hypersensitivity pneumonia in a schoolchild admitted to the hospital's asthma clinic. AB - Bird fancier's lung (BFL), also called bird-breeder's lung or pigeon-breeder's disease (PBD), is a hypersensitivity pneumonitis (HP) that is rare in children. A 9-year-old male patient complained of cough, dyspnea and chest pain, in his examination his lips were cyanosed and his SaO2 was 86% at room air. Bilateral crepitant rales and sibilant rhochi were also detected. In his thoracic computerized tomography, the ground glass areas were noted in both lungs. In his medical history, it was discovered that he lived above an office in which birds and bird manure were merchandised. Precipitant antibody level was determined. Since the levels of precipitant antibody were high and symptoms reappeared with natural provocation, our patient was diagnosed with PBD. The case diagnosed as BFL was presented in this study as an HP which should be considered in the differential diagnosis of children with respiratory distress syndrome and asthma clinic. PMID- 27411426 TI - A rare but important adverse effect of tacrolimus in a heart transplant recipient: diabetic ketoacidosis. AB - Heart transplantation indications in pediatric population include congenital heart diseases, cardiomyopathies and retransplants. Cardiomyopathy is the primary indication for 11 to 17 years of age. The surveillance after transplantation is a very important issue because of both the rejection risk and the adverse effects due to medications after transplantation. Immunosuppressive agents that are commonly used after heart transplantations have several toxicities. Here we present an adolescent patient diagnosed with dilated cardiomyopathy, performed heart transplantation, treated with tacrolimus and suffered from diabetic ketoacidosis due to tacrolimus. After the diagnosis was made the appropriate fluid and insulin therapy was started immediately and ketoacidosis resolved in the first 24 hours of the therapy. The diagnosis revised as new onset diabetes mellitus after transplantation and the tacrolimus dosage titrated to therapeutic level. After glycemic control the patient discharged with rapid acting insulin, three times daily, before meals; and long acting insulin once daily at night. In ten month follow up time the insulin dosages were progressively reduced. PMID- 27411427 TI - Can Burkitt's Lymphoma and Hodgkin's Lymphoma occur in siblings simultaneously? AB - Familial clustering of Hodgkin lymphoma (HL) and increased risk of developing disease among the siblings has been reported earlier. Usually familial lymphoma in sibling pairs occurs in the pairs of either non-Hodgkin lymphoma or HL. In the familial HL, same type of human leukocyte antigens (HLA) is responsible in the affected family members. There are also some studies stating "Killer cell immunoglobulin like receptor (KIR)" genotypes can be important in the etiology of familial HL. Here we report two siblings; one with Non-Hodgkin and the other with Hodgkin lymphoma which showed Epstein-Barr virus encoded small RNAs positivity in the tumor tissues. We have also found that their HLA genotypes are same with each other. In addition, we have discussed familial lymphoma pathogenesis and HLA haplotypes. PMID- 27411428 TI - DRESS Syndrome Presents as Leukoencephalopathy. AB - DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is a potentially life-threatening syndrome, which reflects a serious hypersensitivity reaction to drugs, presenting by generalized skin rash, fever, eosinophilia, atypical lymphocytosis, and internal organ involvement. Herein a 21-month old male infant with DRESS and Encephalopathy syndrome is presented who complicated after phenobarbital usage that persisted due to phenytoin cream usage. The case received phenobarbital after a seizure disorder presented as "status epilepticus". He developed drug eruption, fever, hepatosplenomegaly, increased liver enzymes, encephalopathy and progressive loss of consciousness with extensive hyperintense white matter lesions in brain MRI. After discontinuation of phenobarbital and phenytoin, all symptoms were resolved, while brain MRI became normal after two months. To our best knowledge, this is the first reported case that developed leukoencephalopathy along with DRESS syndrome. PMID- 27411430 TI - The DIPP project: 20 years of discovery in type 1 diabetes. PMID- 27411429 TI - Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis. AB - BACKGROUND: Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis (RA), but its clinical efficacy and safety remain largely undefined in comparison with conventional synthetic disease modifying anti rheumatic drugs (DMARDs). METHODS: PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang Databases. Endpoints were ACR 20, 50, and 70, and the number of withdrawals due to adverse events. Initially, traditional pairwise meta-analysis was performed by using a random-effects model. Then, we performed network meta analysis to compare different therapies by using frequentist approach. RESULTS: A total of 22 trials (5255 participants) were identified. By direct comparison, TwHF was superior to sulphasalazine according to ACR 20, 50 and 70. TwHF was superior to placebo according to ACR 20 and 50. By indirect comparisons, TwHF was superior to methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline and placebo according to ACR 20. Ranking by the Surface under the Cumulative Ranking curve (SUCRA) values showed that TwHF had the greatest probability for being the best treatment option according to ACR 20 (92.0 %) and ACR 50 (81.3 %), and the highest probability to be in the second (57.8 %) ranking position after leflunomide (69.6 %) according to ACR 70. By both direct and indirect comparisons, TwHF caused no more significant withdrawals than the placebo. The SUCRA values showed that TwHF had the highest probability to rank sixth (26.7 %) after the placebo (45.6 %) in causing withdrawals. CONCLUSIONS: Our data suggest that TwHF is effective and safe in the treatment of RA and has better clinical efficacy in terms of ACR 20 and 50 than existing conventional synthetic DMARDs. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted. PMID- 27411431 TI - Genetic susceptibility to type 1 diabetes in childhood - estimation of HLA class II associated disease risk and class II effect in various phases of islet autoimmunity. AB - OBJECTIVE: The HLA-DR/DQ region remains the major determinant of susceptibility to type 1 diabetes (T1D) despite the more than 50 risk affecting loci outside human leukocyte antigen (HLA) region that have been identified. We aimed at developing a simple risk estimation based on HLA class II genotyping, which was also tested by analyzing HLA class II effect on the autoantibody seroconversion and further progression to diabetes. SUBJECTS AND METHODS: A total of 2991 trio families with a diabetic child from the Finnish Pediatric Diabetes Register were genotyped and the risk contributed by each DR-DQ haplotype calculated through transmission analysis. The genotype risk was estimated based on the summary effect of haplotypes. Genotype grouping was further tested in a subcohort of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study RESULTS: The summary effect of haplotypes was generally seen in genotypes, while the expected synergistic effect of DR3-DQ2 and DR4-DQ8 (DRB1*04:03 excluded) combination was also clear in the T1D risk association analysis. This highest risk DR/DQ genotype was found in 21.6% of patients and 2.0% of controls, odds ratio (OR) = 13.2 (10.1 17.2), whereas the lowest risk genotype contained only 0.8% of patients and 28.0% of controls, OR = 0.02 (0.01-0.03). In the subcohort from the DIPP study the risk grades correlated clearly with seroconversion for islet autoantibodies and T1D development. In contrast, DR/DQ risk groups did not associate with the progression rate from advanced autoimmunity to clinical diabetes. CONCLUSIONS: Class II HLA genotype groups improve the estimation of T1D risk. Class II effect is limited to the early phase of the disease process characterized by seroconversion for islet autoantibodies. PMID- 27411432 TI - Role of humoral beta-cell autoimmunity in type 1 diabetes. AB - Islet cell antibodies (ICA) were found for the first time more than 40 yr ago in patients with autoimmune endocrine deficiencies, including type 1 diabetes (T1D). ICA detected by indirect immunofluorescence represent a heterogeneous group of autoantibodies targeting a series of biochemical autoantigens, such as the protein tyrosine phosphatase related islet antigen 2 (IA-2), the 65 kD isoform of glutamic acid decarboxylase (GA65), and zinc transporter 8 (ZnT8) as well as currently unidentified autoantigens. The general view is that the diabetes associated autoantibodies are not directly involved in beta-cell destruction but function as biomarkers of an ongoing destructive process. The diabetes-associated autoantibodies remain the strongest predictive marker for future development of T1D. Positivity for multiple (>=2) autoantibodies is highly predictive of clinical disease both among first-degree relatives and in the general population. Autoantibody titers are highly variable during the preclinical phase, but in many cases the titers tend to decrease before diagnosis. The first signs of beta-cell autoimmunity may appear early during the first months of life. The majority of those individuals diagnosed with T1D before puberty seroconvert to autoantibody positivity before the age of 3 yr. The natural course and duration of preclinical diabetes vary substantially from one individual to another. The characteristics of the isotype-specific response during preclinical diabetes appear to be antigen specific. Diabetes-associated autoantibodies may be useful surrogate markers of the subsequent development of T1D in primary prevention trials. T1D may occur, albeit rarely, in the absence of any signs of humoral autoimmunity at diagnosis. PMID- 27411433 TI - Dysregulation of glucose metabolism in preclinical type 1 diabetes. AB - Long-term prospective studies have provided valuable information about preclinical type 1 diabetes (T1D). Children who have seroconverted to positive for islet autoantibodies have also, in follow-up, had metabolic tests to understand the timing and development of abnormal glucose tolerance and declining insulin secretion before the clinical diagnosis of T1D. First phase insulin response (FPIR) in the intravenous glucose tolerance test (IVGTT) is lower in the progressors positive for multiple islet autoantibodies in all age groups and as early as 4-6 years before the diagnosis when compared with the non-progressors positive for only islet cell antibodies (ICA). An accelerated decline in FPIR is seen in the progressors during the last 1.5 years before the diagnosis. These results indicate that the progressors may have an early intrinsic defect in beta cell development or function. In the oral glucose tolerance test (OGTT) the peak C-peptide response is delayed in the progressors at least 2 years before diagnosis. Glucose levels and HbA1c are increasing about 2 years before clinical diagnosis. An increase in HbA1c and detection of abnormal glucose tolerance in OGTT are useful in the prediction of the timing of clinical onset of T1D. Continuous glucose monitoring (CGM) may be useful in the prediction of T1D as an early indicator of increased glycemic variability but more data from larger series are needed for confirmation. Children followed in the prospective studies are diagnosed earlier and have a decreased frequency of ketoacidosis at the diagnosis of T1D when compared with age-matched cases from the population. PMID- 27411435 TI - Effects of the genome on immune regulation in type 1 diabetes. AB - Type 1 diabetes (T1DM) is a complex disease, arising through the interaction of an incompletely defined combination of genetic susceptibility and environmental factors. It is well accepted that T1DM results from selective immune-mediated destruction of the insulin-producing beta cells in the islets of langerhans. Genetic studies of T1DM have identified several regions of susceptibility and identified major networks and pathways contributing to risk. In this study, we have taken advantages of the Immunochip fine-mapping genotyping data to address different aspects of immune regulation in relation to T1DM. First, we confirm that dense single nucleotide polymorphism (SNP) genotyping of the major histocompatibility complex/human leukocyte antigen (MHC/HLA) region capture the complex genetic contribution of this region to disease risk. Furthermore, it is shown that Immunochip genotyping can translate into a limited number of DRB1 and DQB1 amino acid residues that account for most of the HLA-risk. Second, we use the Immunochip data to look for functional significance by correlation to circulating levels of chemokines and demonstrate that genetic variation at chromosome 2, 3, and 6 correlates with circulating CCL2 and CCL4 in recent onset T1DM patients. Finally, we report that genetic variants predict autoantibody positivity in T1DM cases. PMID- 27411434 TI - Insulitis in the pathogenesis of type 1 diabetes. AB - Type 1 diabetes (T1D) is a chronic autoimmune disease in which autoreactive T cells and inflammation cause severe loss of pancreatic beta cells. Insulitis, the pathologic hallmark of T1D, is an inflammatory lesion consisting of immune cell infiltrates around and within the islets. New research initiatives and methodologies are advancing our understanding of pancreas pathology. Studies have revealed the predominant cellular types that infiltrate the islets, novel molecular aspects associated with insulitis, and the coexistence of additional pathological abnormalities. While insulitis is a critical element of T1D pathology and pathogenesis, it is typically present only in a modest proportion of islets at any given time, even at diagnosis, with overall limited relation to disease duration. Thus, the relative importance of insulitis as a determining factor of diabetes symptoms at disease onset appears to have been overestimated; growing evidence also shows that beta cell loss at diagnosis is more modest than previously thought. Thus, the sole targeting of the immune system may not afford full therapeutic efficacy if dysfunction affects beta cells that are not under immune attack and this is a key contributor to symptoms. Combination therapies that promote both immunoregulation and address beta cell dysfunction should be more effective in treating this chronic disease process. It remains a major goal to clarify the relation of insulitis with the dynamics of beta cell loss and coexisting mechanisms of dysfunction, according to clinical stage; such improved understanding is key to design therapeutic strategies that target multiple pathogenic mechanisms. PMID- 27411436 TI - Early signs of disease in type 1 diabetes. AB - As a severe chronic disease with long-term complications, type 1 diabetes (T1D) is a burden to the patients and their families as well as a challenge to the health care system. T1D is a heterogeneous disease with a variety of etiologies and a wide range in the rate of progression to the disease. In order to prevent and treat T1D it would be important to identify measures that could be used to predict and monitor disease progression, as well as to further understand the molecular mechanisms involved. During the past 20 yr since its initiation, the Finnish Diabetes Prediction and Prevention Project (DIPP) has collected longitudinal biological samples from children with a human leukocyte antigen gene conferred risk of T1D. This large sample collection has provided detailed sample series that enable studies to map the progression from health to disease, as well as the healthy maturation of risk-matched children. The DIPP samples have been used in a large body of research to elucidate the factors involved in the development of T1D. Interestingly, results from recent studies exploiting omics platforms have revealed that signs of the disease process can be detected very early on, even prior to appearance of the first T1D-associated antibodies, which are currently considered the earliest indications of the emerging disease. Identification and validation of multi-modal molecular markers will we hope provide a means to subgroup the heterogeneous group of T1D patients and enable prediction, diagnosis, and monitoring of T1D. Discovery of such markers is important in the design and testing of prevention and therapies for T1D. PMID- 27411437 TI - Dietary factors in the development of type 1 diabetes. AB - There are several indicators concerning the putative importance of dietary factors during the fetal period lactation, infancy and childhood in the etiology of type 1 diabetes. Among foods, cow's milk consumption has been associated with an increased risk of preclinical and/or clinical type 1 diabetes and sugars with a progression from preclinical to clinical disease. Breast milk, on the other hand, may be protective. Processed foods may be related to a greater risk of type 1 diabetes because they contain higher amounts of advanced glycation end products. Nitrites or N-nitroso compounds in processed meat products could increase the risk of this disease. Among nutrients, n-3 fatty acids, vitamins D and E, and zinc may protect from preclinical and/or clinical type 1 diabetes. The microbial composition of foods or food's other effects on gut microbiota are receiving increasing attention, also due to their putative role in the development of type 1 diabetes. Still the number of prospective studies in this research field is limited and most of the findings remain to be replicated. PMID- 27411438 TI - Viruses in type 1 diabetes. AB - Environmental factors play an important role in the pathogenesis of type 1 diabetes and can determine if a genetically susceptible individual develops the disease. Increasing evidence suggest that among other exogenous agents certain virus infections can contribute to the beta-cell damaging process. Possible viral etiology of type 1 diabetes has been explored extensively but the final proof for causality is still lacking. Currently, the group of enteroviruses (EVs) is considered as the strongest candidate. These viruses have been found in the pancreas of type 1 diabetic patients, and epidemiological studies have shown more EV infections in diabetic patients than in controls. Prospective studies, such as the Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland, are of fundamental importance in the evaluation viral effects as they can cover all stages of the beta-cell damaging process, including those preceding the initiation of the process. DIPP study has carried out the most comprehensive virological analyses ever done in prospective cohorts. This article summarizes the findings from these analyses and discuss them in the context of the existing other knowledge and the prospects for intervention studies with EV vaccines or antiviral drugs. PMID- 27411439 TI - Environmental factors in the etiology of type 1 diabetes, celiac disease, and narcolepsy. AB - The etiology of human leukocyte antigen (HLA)-associated organ-specific autoimmune diseases is incomplete. In type 1 diabetes and celiac disease, the strongest associations are with the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, whereas the DQB1*06:02 allele has a strong negative association. In contrast, narcolepsy, especially as recently triggered by the Pandemrix((r)) H1N1 vaccine (GlaxoKlineSmith (GSK), Brentford, Middlesex, UK), did not seem to develop without at least one copy of the latter allele. The overall hypothesis is that the role of these different HLA haplotypes, especially in Finland and Sweden, is related to the immune response to infectious agents that are common in these two populations. The high incidence of both type 1 diabetes and celiac disease in Scandinavia may be the result of the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, and the DQB1*06:02 allele are common because they protected people from succumbing to common infections. The timing of dissecting the autoimmune response is critical to understand the possible role of environmental factors. First, an etiological trigger may be a common virus infecting beta cells or with antigens inducing beta cell cross reactivity. Second, an autoimmune reaction may ensue, perhaps in response to beta-cell apoptosis or autophagy, resulting in autoantigen-specific T cells and autoantibodies. It is critical in at-risk children to dissect the immune response prior to the appearance of autoantibodies in order to identify cellular reactions in response to environmental factors that are able to induce an HLA-associated immune reaction. PMID- 27411441 TI - Current and future efforts toward the prevention of type 1 diabetes. AB - Great strides have been made in our understanding of the natural history of 'pre type 1' diabetes as well as in the post diagnosis period. For now, an inability to successfully prevent the disease limits screening outside of the research setting. While studies of both humans with various levels of risk for type 1 diabetes as well as animal models for the disease have increased our understanding of the disorder, the development of a safe and effective therapeutic intervention capable of reversing or preventing type 1 diabetes remains elusive. Worldwide primary, secondary, and tertiary prevention studies have been undertaken and both past and current studies are extensively reviewed in this manuscript. Intervention studies in new-onset and established type 1 diabetes patients have to date shown fairly limited success with most effects seen within the first 6-12 months post therapy. Long-term outcome remains to be determined. Improved and innovative trial designs, more rapid testing of both antigen specific and combination therapies in different populations (at-risk, new onset, and established type 1 diabetes), continuing to fill the mechanistic voids in the etiopathogenesis of type 1 diabetes, and the development of validated biomarkers will hasten efforts toward reversing and preventing the disease. For successful prevention, therapy must be safe and must target not only effective control of the autoimmune process culminating in type 1 diabetes but also protection or replacement of lost beta-cell function. PMID- 27411440 TI - A Swedish approach to the prevention of type 1 diabetes. AB - BACKGROUND: The autoimmune destruction of beta cells, resulting in clinical type 1 diabetes, may start early in life and last for several months or years. During this period of time, we have an opportunity to try to prevent or delay further beta-cell destruction and clinical onset of type 1 diabetes. OBJECTIVES: Ongoing prediction and prevention studies in Skane, Sweden are described. METHODS: During September 2000 to August 2004, 35 000 children were screened at birth for genetic type 1 diabetes risk in the Diabetes Prediction in Skane Study (DiPiS). In August 2004, the screening continued within the Enviromnental Determinants of Diabetes in the Young study (TEDDY). In the clinical trial Diabetes Prevention - Immune Tolerance (DiAPREV-IT), children with multiple islet autoimmunity have been included to investigate if immune tolerance with Alum-formulated GAD65 may prevent further beta-cell loss. RESULTS: In DiPiS and TEDDY, a large number of children are followed in order to find the factors that trigger the autoimmune process leading to type 1 diabetes. Children followed in the studies develop diabetes at an early stage of disease, with few symptoms and a low frequency of diabetes ketoacidosis. DiAPREV-IT is still blinded and results will be available in December 2016. CONCLUSION: Large prospective studies will be needed to understand the complex process leading to type 1 diabetes. Secondary prevention may be possible in children with islet autoimmunity, but the studies are complicated by the variability of glucose metabolism and beta-cell loss. PMID- 27411442 TI - JDRF's vision and strategy for prevention of type 1 diabetes. AB - The increasing incidence and lower threshold of developing type 1 diabetes (T1D) increases the urgency of its prevention. Insights from past and current natural history studies have provided the framework for a compelling strategy for primary and secondary prevention. Primary prevention of T1D should target the general childhood population with vaccines (viral or tolerogenic) or by altering microbiota-induced immunoregulation. Secondary prevention will likely require combination therapies (anti-inflammatories, immunomodulatory agents, beta cell survival agents, and/or agents improving glucose control) used sequentially or simultaneously to preserve residual beta cell function and prevent symptomatic disease. Critical gaps and challenges for prevention of T1D include an incomplete understanding of disease pathogenesis and heterogeneity, the lack of cost effective risk screening and validated biomarkers for precise staging of disease and optimizing design of shorter and smaller prevention clinical trials, and the lack of appreciation of the impact and burden of T1D and the potential for its prevention. A comprehensive and concerted effort of funders, academia, industry, regulatory authorities, payers, government bodies, health care providers, and the T1D community will be required to deliver on JDRF's vision and strategy for prevention of T1D. PMID- 27411445 TI - Transitions in a genetic transcriptional regulatory system under Levy motion. AB - Based on a stochastic differential equation model for a single genetic regulatory system, we examine the dynamical effects of noisy fluctuations, arising in the synthesis reaction, on the evolution of the transcription factor activator in terms of its concentration. The fluctuations are modeled by Brownian motion and alpha-stable Levy motion. Two deterministic quantities, the mean first exit time (MFET) and the first escape probability (FEP), are used to analyse the transitions from the low to high concentration states. A shorter MFET or higher FEP in the low concentration region facilitates such a transition. We have observed that higher noise intensities and larger jumps of the Levy motion shortens the MFET and thus benefits transitions. The Levy motion activates a transition from the low concentration region to the non-adjacent high concentration region, while Brownian motion can not induce this phenomenon. There are optimal proportions of Gaussian and non-Gaussian noises, which maximise the quantities MFET and FEP for each concentration, when the total sum of noise intensities are kept constant. Because a weaker stability indicates a higher transition probability, a new geometric concept is introduced to quantify the basin stability of the low concentration region, characterised by the escaping behaviour. PMID- 27411444 TI - Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks? AB - BACKGROUND: Diagnosing systemic juvenile idiopathic arthritis (SJIA) can be extremely challenging if typical arthritis is lacking. A variety of biomarkers have been described for the diagnosis and management of SJIA. However, very few markers have been well-validated. In addition, increasing numbers of biomarkers are identified by high throughput or multi-marker panels. METHOD: We identified diagnostic or prognostic biomarkers by systematic literature review, evaluating each according to a predefined level of verification, validation or clinical utility. Diagnostic biomarkers were those identifying SJIA versus (1) non-SJIA conditions or healthy controls (HC) or (2) other non-systemic JIA subtypes. Prognostic biomarkers were those specifically tested for the prediction of (1) disease flare, (2) increased disease activity +/- discrimination of active versus inactive disease, or (3) macrophage activation syndrome (MAS). RESULTS: Fifty five studies fulfilled the inclusion criteria identifying 68 unique biomarkers, of which 50/68 (74 %) were investigated by only a single research group. Candidate marker verification and clinical utility was evaluated according to whether markers were readily and reliably measurable, investigated by independent study groups, discovered by more than one method (i.e. verified markers) and validated in independent cohorts. This evaluation revealed diagnostic biomarkers of high interest for further evaluation in the diagnostic approach to SJIA that included heme oxygenase-1, interleukin-6 (IL-6), IL-12, IL-18, osteoprotegerin, S100 calcium-binding protein A12 (S100A12) and S100A8/A9. CONCLUSION: In summary, a number of biomarkers were identified, though most had limited evidence for their use. However, our findings combined with the identified studies could inform validation studies, whether in single or multi-marker assays, which are urgently needed. PMID- 27411446 TI - The association between seeking financial compensation and injury recovery following motor vehicle related orthopaedic trauma. AB - BACKGROUND: Motor vehicle related moderate-severe orthopaedic trauma has a major impact on the burden of injury. In Australia, all states and territories provide access to financial compensation following injury in a motor vehicle crash. The aim of this study was to investigate the influence of seeking financial compensation (i.e., making a claim) on injury recovery following motor vehicle related moderate-severe orthopaedic trauma. METHODS: Patients admitted with upper/lower extremity fractures after a motor vehicle crash were recruited from two trauma hospitals. Baseline data were collected in person by written questionnaire within two weeks of injury. Follow up data were collected by a mailed written questionnaire at six, 12 and 24 months. Additional (demographic/injury-related) information was collected from hospital databases, all other measures were self-reported. Outcomes were: Short Form-36 Version 2.0 (SF36v2), Physical/Mental Component Scores (PCS/MCS); Post Traumatic Stress Disorder (PTSD) Checklist Civilian Version (PCL-C); and Global Rating of Change (GRC) scale. Analysis involved descriptive statistics and linear mixed models to examine the effect of compensation status on injury recovery over time. RESULTS: There were 452 study participants. Baseline characteristics showed: mean age 40 years (17.1 Standard Deviation [SD]); 75 % male; 74 % worked pre-injury; 67 % in excellent-very good pre-injury health; 56 % sustained serious injuries, Injury Severity Score (ISS) 9-15; 61 % had a low-middle range household income. Overall, after controlling for possible confounders, the compensable group had poorer recovery compared to the non-compensable group for PCS (-2.97 Mean Difference (MD), 95 % CI -4.73, -1.22); MCS (-3.44 MD, 95 % CI -5.62, -1.26); PCL-C (3.42MD, 95 % CI 0.87, 5.99); and GRC (-0.66MD, 95 % CI -1.15, -0.17). Injury recovery over time for all participants showed: PCS improved from 6-12 and 12-24 months; MCS and GRC improved from 6-12 months; and PCL-C did not significantly improve from 6-12 and 12-24 months. Injury recovery over time continued for compensable and non-compensable groups but compensable participants had poorer scores at each time period, especially MCS and PCL-C. CONCLUSIONS: Making a claim was associated with poor injury recovery following motor vehicle related orthopaedic trauma, mainly for mental health. Irrespective of claim status, the majority had poor injury recovery, especially for mental health. PMID- 27411447 TI - Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking beta(1,3)-glucan remodeling. AB - BACKGROUND: The cell wall is essential for the yeast to hypha (Y-H) transition that enables Candida albicans to invade human tissues and evade the immune system. The main constituent, beta(1,3)-glucan, is remodeled by glucanosyltransferases of the GH72 family. Phr1p is responsible of glucan remodeling at neutral-alkaline pH and is essential for morphogenesis and virulence. Due to the pH-regulated expression of PHR1, the phr1Delta phenotype is manifested at pH > 6 and its severity increases with the rise in pH. We exploited the pH-conditional nature of a PHR1 null mutant to analyze the impact of glucan remodeling on the hyphal transcriptional program and the role of chitin synthases in the hyphal wall stress (HWS) response. RESULTS: In hyphal growth inducing conditions, phr1Delta germ tubes are defective in elongation, accumulate chitin, and constitutively activate the signaling pathways mediated by the MAP kinases Mkc1p, Cek1p and Hog1p. The transcriptional profiles revealed an increase of transcript levels for genes involved in cell wall formation (CHS2 and CHS8, CRH11, PGA23, orf19.750, RBR1, RBT4, ECM331, PGA6, PGA13), protein N glycosylation and sorting in the ER (CWH8 and CHS7), signaling (CPP1, SSK2), ion transport (FLC2, YVC1), stress response and metabolism and a reduced expression of adhesins. A transient up-regulation of DNA replication genes associated with entry into S-phase occurred whereas cell-cycle regulating genes (PCL1, PCL2, CCN1, GIN4, DUN1, CDC28) were persistently up-regulated. To test the physiological relevance of altered CHS gene expression, phr1Delta chsxDelta (x = 2,3,8) mutant phenotypes were analyzed during the Y-H transition. PHR1 deletion was synthetic lethal with CHS3 loss on solid M199 medium-pH 7.5 and with CHS8 deletion on solid M199-pH 8. On Spider medium, PHR1 was synthetic lethal with CHS3 or CHS8 at pH 8. CONCLUSIONS: The absence of Phr1p triggers an adaptive response aimed to reinforce the hyphal cell wall and restore homeostasis. Chs3p is essential in preserving phr1Delta cell integrity during the Y-H transition. Our findings also unveiled an unanticipated essential role of Chs8p during filamentation on solid media. These results highlight the flexibility of fungal cells in maintaining cell wall integrity and contribute to assessments of glucan remodeling as a target for therapy. PMID- 27411448 TI - Direct interaction with ACR11 is necessary for post-transcriptional control of GLU1-encoded ferredoxin-dependent glutamate synthase in leaves. AB - Because it plays an essential role in nitrogen (N) assimilation and photorespiration, the glutamine synthetase (GS)/glutamate synthase (GOGAT) system is widely accepted as occupying a central position in leaf N metabolism. However, the regulation of GOGAT at the post-transcriptional level is poorly understood. Here, we show that ACR11, an ACT (acronym for aspartate kinase, chorismate mutase, and TyrA) domain-containing family protein, interacts with Glu1-encoded ferredoxin (Fd)-GOGAT in Arabidopsis chloroplasts. In addition, Arabidopsis acr11 mutants have lost the capability to control Fd-GOGAT levels in response to light/dark diurnal cycles, nitrogen inputs, and changes in photorespiratory activity. Considering that ACR11 has putative glutamine-binding domains, our results indicate that ACR11 is necessary for post-transcriptional control of leaf Glu1-encoded Fd-GOGAT. This regulation takes place through direct interaction of ACR11 and Fd-GOGAT, possibly in an allosteric manner. PMID- 27411449 TI - Gut Microbiota and Intestinal Decolonization of Pathogenic Microorganisms. PMID- 27411451 TI - Physiological Correlation of Airway Pressure and Transpulmonary Pressure Stress Index on Respiratory Mechanics in Acute Respiratory Failure. AB - BACKGROUND: Stress index at post-recruitment maneuvers could be a method of positive end-expiratory pressure (PEEP) titration in acute respiratory distress syndrome (ARDS) patients. However, airway pressure (Paw) stress index may not reflect lung mechanics in the patients with high chest wall elastance. This study was to evaluate the Pawstress index on lung mechanics and the correlation between Pawstress index and transpulmonary pressure (PL) stress index in acute respiratory failure (ARF) patients. METHODS: Twenty-four ARF patients with mechanical ventilation (MV) were consecutively recruited from July 2011 to April 2013 in Zhongda Hospital, Nanjing, China and Ospedale S. Giovanni Battista Molinette Hospital, Turin, Italy. All patients underwent MV with volume control (tidal volume 6 ml/kg) for 20 min. PEEP was set according to the ARDSnet study protocol. The patients were divided into two groups according to the chest wall elastance/respiratory system elastance ratio. The high elastance group (H group, n = 14) had a ratio >=30%, and the low elastance group (L group, n = 10) had a ratio <30%. Respiratory elastance, gas-exchange, Pawstress index, and PLstress index were measured. Student's t-test, regression analysis, and Bland-Altman analysis were used for statistical analysis. RESULTS: Pneumonia was the major cause of respiratory failure (71.0%). Compared with the L group, PEEP was lower in the H group (5.7 +/- 1.7 cmH2O vs. 9.0 +/- 2.3 cmH2O, P < 0.01). Compared with the H group, lung elastance was higher (20.0 +/- 7.8 cmH2O/L vs. 11.6 +/- 3.6 cmH2O/L, P < 0.01), and stress was higher in the L group (7.0 +/- 1.9 vs. 4.9 +/- 1.9, P = 0.02). A linear relationship was observed between the Pawstress index and the PLstress index in H group (R2 = 0.56, P < 0.01) and L group (R2 = 0.85, P < 0.01). CONCLUSION: In the ARF patients with MV, Pawstress index can substitute for PLto guide ventilator settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02196870 (https://clinicaltrials.gov/ct2/show/NCT02196870). PMID- 27411452 TI - Efficacy and Safety of Esmolol in Treatment of Patients with Septic Shock. AB - BACKGROUND: Previous studies have suggested that beta1-receptor blockers benefit septic shock patients. This study aimed to determine whether beta1-receptor blockers benefit tissue perfusion in sepsis and to identify parameters to reduce the risk of this drug in sepsis. METHODS: Consecutive septic shock patients were recruited from the Intensive Care Unit of Peking Union Medical College Hospital within 48 h of diagnosis. All patients were hemodynamically stable and satisfactorily sedated with a heart rate (HR) >=100 beats/min. Esmolol therapy achieved the target HR of 10-15% lower than the baseline HR. Clinical and physiological data of patients were collected prospectively within 1 h prior to esmolol therapy and 2 h after achieving the targeted HR. RESULTS: Sixty-three patients were recruited. After esmolol therapy, blood pressure was unaltered, whereas stroke volume (SV) was increased compared with before esmolol therapy (43.6 +/- 22.7 vs. 49.9 +/- 23.7 ml, t = -2.3, P = 0.047). Tissue perfusion, including lactate levels (1.4 +/- 0.8 vs. 1.1 +/- 0.6 mmol/L, t = 2.6, P = 0.015) and the central venous-to-arterial carbon dioxide difference (5.6 +/- 3.3 vs. 4.3 +/- 2.2 mmHg, t = 2.6 P = 0.016), was also significantly decreased after esmolol therapy. For patients with increased SV (n = 42), cardiac efficiency improved, and esmolol therapy had a lower risk for a decrease in cardiac output (CO). Therefore, pretreatment cardiac systolic and diastolic parameters with (n = 42)/without (n = 21) an increase in SV were compared. Mitral lateral annular plane systolic excursion (MAPSElat) in patients with increased SV was significantly higher than that in those without increased SV (1.3 +/- 0.3 vs. 1.1 +/- 0.2 cm, t = 2.4, P = 0.034). CONCLUSIONS: SV of septic shock patients is increased following esmolol therapy. Although CO is also decreased with HR, tissue perfusion is not worse. MAPSElat can be used to predict an increase in SV before esmolol use. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01920776; https://clinicaltrials.gov/ct2/show/NCT01920776?term=NCT01920776&rank=1. PMID- 27411450 TI - Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross sectional Study and Questionnaire Survey in China. AB - BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale <=8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073. PMID- 27411453 TI - Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal directed Therapy. AB - BACKGROUND: Early goal-directed therapy (EGDT) has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients. METHODS: A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients' characteristics were compared before treatment (T0), immediately after EGDT (T1), and 24 h after EGDT (T2). This study is registered at ClinicalTrials.org, NCT02060773. RESULTS: Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients; therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate (ICG-PDR) and 15-min retention rate (R15) at T0 (11.9 +/- 5.0%/min and 20.0 +/- 13.2%), T1 (11.4 +/- 5.1%/min and 23.6 +/- 14.9%), and T2 (11.0 +/- 4.5%/min and 23.7 +/- 15.3%) (all P > 0.05). Both of the alterations of ICG-PDR and R15 showed no differences at T0, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected (P > 0.05). CONCLUSION: There were no hepatic perfusion improvements after EGDT in the early phase of patients with septic shock. TRIAL REGISTRATION: Clinicaltrials.gov NCT02060773 (https://clinicaltrials.gov/ct2/show/NCT02060773). PMID- 27411455 TI - Determinants of Calcium Infusion Rate During Continuous Veno-venous Hemofiltration with Regional Citrate Anticoagulation in Critically Ill Patients with Acute Kidney Injury. AB - BACKGROUND: It is unclear that how to decide the calcium infusion rate during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to assess the determinants of calcium infusion rate during CVVH with RCA in critically ill patients with acute kidney injury (AKI). METHODS: A total of 18 patients with AKI requiring CVVH were prospectively analyzed. Postdilution CVVH was performed with a fixed blood flow rate of 150 ml/min and a replacement fluid flow rate of 2000 ml/h for each new circuit. The infusion of 4% trisodium citrate was started at a rate of 29.9 mmol/h prefilter and adjusted according to postfilter ionized calcium. The infusion of 10% calcium gluconate was initiated at a rate of 5.5 mmol/h and adjusted according to systemic ionized calcium. The infusion rate of trisodium citrate and calcium gluconate as well as ultrafiltrate flow rate were recorded at 1, 2, 4, 6, 12, and 24 h after starting CVVH, respectively. The calcium loss rate by CVVH was also calculated. RESULTS: Fifty-seven sessions of CVVH were performed in 18 AKI patients. The citrate infusion rate, calcium loss rate by CVVH, and calcium infusion rate were 31.30 (interquartile range: 2.70), 4.60 +/- 0.48, and 5.50 +/- 0.35 mmol/h, respectively. The calcium infusion rate was significantly higher than that of calcium loss rate by CVVH (P < 0.01). The correlation coefficient between the calcium and citrate infusion rates, and calcium infusion and calcium loss rates by CVVH was -0.031 (P > 0.05) and 0.932 (P < 0.01), respectively. In addition, calcium infusion rate (mmol/h) = 1.77 + 0.8 * (calcium loss rate by CVVH, mmol/h). CONCLUSIONS: The calcium infusion rate correlates significantly with the calcium loss rate by CVVH but not with the citrate infusion rate in a fixed blood flow rate during CVVH with RCA. PMID- 27411454 TI - Diagnostic and Predictive Levels of Calcium-binding Protein A8 and Tumor Necrosis Factor Receptor-associated Factor 6 in Sepsis-associated Encephalopathy: A Prospective Observational Study. AB - BACKGROUND: Despite its high prevalence, morbidity, and mortality, sepsis associated encephalopathy (SAE) is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 (S100A8) in serum and tumor necrosis factor receptor-associated factor 6 (TRAF6) in peripheral blood mononuclear cells (PBMCs) in diagnosing SAE and predicting its prognosis. METHODS: Data of septic patients were collected within 24 h after Intensive Care Unit admission from July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfunction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S100A8, S100beta, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S100A8 were also measured in the control group. RESULTS: Of the 57 enrolled patients, 29 were diagnosed with SAE. The S100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no encephalopathy (NE) patients, and higher in NE than that in controls (3.74 +/- 3.13 vs. 1.08 +/- 0.75 vs. 0.37 +/- 0.14 ng/ml, P < 0.01; 3.18 +/- 1.55 vs. 1.02 +/- 0.63 vs. 0.47 +/- 0.10, P < 0.01). S100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic (ROC) curve, and the area under the curve was 0.86 (95% confidence interval [CI]: 0.76-0.95). TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 (95% CI: 0.88-0.99). In addition, S100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. CONCLUSIONS: Peripheral blood levels of S100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis. PMID- 27411456 TI - Performance of Multiple Risk Assessment Tools to Predict Mortality for Adult Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation Therapy: An External Validation Study Based on Chinese Single-center Data. AB - BACKGROUND: There has been no external validation of survival prediction models for severe adult respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data. METHODS: A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE (Predicting death for severe ARDS on VV-ECMO), ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score, a center-specific model developed for inter hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC). RESULTS: The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 (95% confidence interval [CI], 0.659-1.010, P = 0.007) and 0.762 (95% CI, 0.558-0.965, P = 0.035), respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 (95% CI, 0.571 1.009, P = 0.038). However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since only one patient died six months postdischarge. CONCLUSIONS: The RESP, APCHAE II, and SOFA scorings systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients' data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted. PMID- 27411457 TI - Role of Osteoprotegerin and Receptor Activator of Nuclear Factor-kappaB Ligand in Bone Loss Related to Advanced Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-MU) with bone turnover in men with very severe COPD. METHODS: Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and beta-CrossLaps (betaCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using an independent t-test and Mann-Whitney U-test. The Pearson coefficient was used to assess the relationships between variables. RESULTS: OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum betaCL, TNF-MU, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEV1) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01). In contrast, serum RANKL inversely associated with LS and FN T-score (r = -0.62, P < 0.001 and r = -0.48, P < 0.001) but directly correlated with betaCL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = -0.39, P < 0.01), TNF-MU (r = -0.56, P < 0.001), and sTNFR-I (r = -0.40, P < 0.01). CONCLUSION: Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD. PMID- 27411458 TI - mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis in Rats. AB - BACKGROUND: Aspergillosis infection is common in the patients with insufficient immunity. The role of mammalian target of rapamycin (mTOR), T-box expressed in T cells (T-bet), and eomesodermin (EOMES) in mediating T lymphocytes differentiation in response to Aspergillus fumigatus infection in immunocompromised rats was investigated in this study. METHODS: Invasive pulmonary aspergillosis (IPA) of immunosuppressive twenty male rats were established and sacrificed at 24 h (n = 5), 48 h (n = 5), 72 h (n = 5), and 96 h (n = 5) after A. fumigatus infection. In addition, control (n = 5), cyclophosphamide (CTX) (n = 5), and aspergillosis (n = 5) group were also established the tissues and pathology of lung tissue was examined by hematoxylin and eosin staining. CD8+ T-cells was sorted by flow cytometry. Serum mTOR, S6K, T bet, and EOMES were quantified by enzyme-linked immunosorbent assay. RESULTS: Histology of lung tissue indicated severe lung tissue injury including infiltration of inflammatory cells, alveolar wall damage or degradation, blood congestion, and hemorrhage in the CTX, IPA, and CTX + IPA rats. Hyphae were seen in the IPA, and CTX + IPA groups. The proportion of CD8+ T-cells was significantly increased in the animals of CTX + IPA. Memory CD8+ T-cells was significantly increased in early stage (24 h and 48 h, P < 0.001), but decreased in the late phase of fungal infection (72 h and 96 h) in the animals of CTX + IPA. In addition, at early stage of fungal infection (24 h and 48 h), serum mTOR (P < 0.001), S6K (P < 0.001), and T-bet (P < 0.05) was significantly higher, while EOMES was significantly lower (P < 0.001), in CTX + IPA group than that in control, CTX alone or IPA alone group. Conversely, serum mTOR, S6K, T-bet, and EOMES showed opposite changed in the late stage (72 h and 96 h). Pearson's correlation analysis indicated that mTOR and S6K were significantly correlated with T-bet (r = 0.901 and 0.91, respectively, P < 0.001), but negatively and significantly correlated with EOMES (r = -0.758 and -0.751, respectively, P < 0.001). CONCLUSIONS: mTOR may regulate transcription factors of EOMES and T-bet, and by which mechanism, it may modulate lymphocytes differentiation in animals with immune suppression and fungal infection. PMID- 27411460 TI - Corrigendum: Interventional Therapy for Bilateral Acute Renal Artery Embolism Caused by Paroxysmal Atrial Fibrillation. AB - [This corrects the article DOI: 10.4103/0366-6999.181956.]. PMID- 27411459 TI - Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats. AB - BACKGROUND: Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI), and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. METHODS: Fifty female Wistar rats were divided into five groups according to the status of C. albicans infection and IIRI operation: group blank and sham; group blank and IIRI; group cefoperazone plus IIRI; group C. albicans plus cefoperazone and IIRI (CCI); and group C. albicans plus cefoperazone and sham. The levels of inflammatory factors tumor necrosis factor (TNF)-MU, interleukin (IL)-6, IL-1beta, and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. RESULTS: The levels of inflammatory factors TNF-MU, IL-6, and IL-1beta in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO (serum: 44.13 +/- 4.30 pg/ml, intestine: 346.21 +/- 37.03 pg/g) and Chiu scores (3.41 +/- 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number of C. albicans translocated into blood was most in group CCI ([33.80 +/- 6.60] *102 colony forming unit (CFU)/ml). CONCLUSION: Intestinal C. albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. albicans translocation and dissemination. PMID- 27411461 TI - Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats. AB - BACKGROUND: An acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (JNK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model. METHODS: Thirty-six rats were randomized into three groups: control, LPS, and LPS + JNK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups. RESULTS: MPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 +/- 0.15 U in LPS vs. 0.77 +/- 0.27 U in control, P < 0.05). Inhibiting JNK attenuated LPS-induced MPO activity upregulation (0.52 +/- 0.12 U in LPS + JNK inhibitor vs. 1.26 +/- 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting JNK attenuated LPS-induced neutrophils increase in BALF (255.0 +/- 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 +/- 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 +/ 4.82 vs. 7.00 +/- 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + JNK inhibitor group. CONCLUSIONS: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory. PMID- 27411462 TI - Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats. AB - BACKGROUND: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. METHODS: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-MU, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. RESULTS: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-MU and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. CONCLUSIONS: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis induced ALI. PMID- 27411463 TI - Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats. AB - BACKGROUND: The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown. The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC). METHODS: A Sprague-Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-MU and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group), with or without VitC treatment before resuscitation, were evaluated. RESULTS: HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflammatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation. CONCLUSIONS: The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC SIGN, and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney. PMID- 27411464 TI - Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability. AB - BACKGROUND: Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability. METHODS: Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers. RESULTS: A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2 carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-beta-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 MUmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 MUmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE cadherin into the culture medium, which was significantly inhibited by the five monomer mixture. CONCLUSIONS: The rhubarb mixture of emodin, 3,8-dihydroxy-1 methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl) beta-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations. PMID- 27411466 TI - Swyer's Syndrome with Mixed Ovarian Malignant Germ Cell Tumor and Ovarian Gonadoblastoma. PMID- 27411465 TI - Multiple Functions of Ten-eleven Translocation 1 during Tumorigenesis. AB - OBJECTIVE: Aberrant expression of ten-eleven translocation 1 (TET1) plays a critical role in tumor development and progression. We systematically summarized the latest research progress on the role and mechanisms of TET1 in cancer biology. DATA SOURCES: Relevant articles published in English from 1980 to April 2016 were selected from the PubMed database. The terms "ten-eleven translocation 1," "5mC," "5hmC," "microRNA," "hypoxia," and "embryonic stem cell" were used for the search. STUDY SELECTION: Articles focusing on the role and mechanism of TET1 in tumor were reviewed, including clinical and basic research articles. RESULTS: TET proteins, the key enzymes converting 5-methylcytosine to 5 hydroxymethylcytosine, play vital roles in DNA demethylation regulation. Recent studies have shown that loss of TET1 is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy, which indicates that TET1 serves as tumor suppressor gene. Moreover, besides its dioxygenase activity, TET1 could induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription, such as developmental regulator in embryonic stem cells (ESCs) and hypoxia-responsive gene in cancer. The regulation of TET1 is also correlated with microRNA in a posttranscriptional modification process. Hence, it is complex but critical to comprehend the mechanisms of TET1 in the biology of ESCs and cancer. CONCLUSIONS: TET1 not only serves as a demethylation enzyme but also plays multiple roles during tumorigenesis and progression. More studies should be carried out to elucidate the exact mechanisms of TET1 and its associations with cancer before considering it as a therapeutic tool. PMID- 27411467 TI - Passive Leg Raising in Intensive Care Medicine. PMID- 27411468 TI - A Case Report of Inversa Acne and Evaluation for Mutations in the NCSTN, PSENEN, and PSEN1 Genes. PMID- 27411469 TI - A Case of Cerebral Fat Embolism. PMID- 27411470 TI - Left-dominant Arrhythmogenic Cardiomyopathy: A Case Misdiagnosed as Pseudoaneurysm. PMID- 27411471 TI - ESBL E coli and P. aeruginosa Resistance to Ceftolozane-Tazobactam in a Patient with a Liver Abscess. The Search for an Omnipotent Antibiotic Goes On! AB - Multi drug resistant (MDR) Pseudomonas aeruginosa and Extended- Spectrum lactamase (ESBL) Enterobacteriaceae are becoming an increasing difficult clinical problem. Immediate resistance to some of the new antimicrobials such as ceftolozane/tazobactam is unusual and is due to a variety of mechanisms such as hyper-production of inactivating enzymes and gene mutation. In addition, previous antimicrobial administration is a well-recognized risk factor to develop resistance. We present a patient with a liver abscess where the organism was resistant to ceftolozane/tazobactam resulting in a poor clinical outcome. PMID- 27411472 TI - Withdrawn PMID- 27411474 TI - Partnership capacity for community health improvement plan implementation: findings from a social network analysis. AB - BACKGROUND: Many health departments collaborate with community organizations on community health improvement processes. While a number of resources exist to plan and implement a community health improvement plan (CHIP), little empirical evidence exists on how to leverage and expand partnerships when implementing a CHIP. The purpose of this study was to identify characteristics of the network involved in implementing the CHIP in one large community. The aims of this analysis are to: 1) identify essential network partners (and thereby highlight potential network gaps), 2) gauge current levels of partner involvement, 3) understand and effectively leverage network resources, and 4) enable a data driven approach for future collaborative network improvements. METHODS: We collected primary data via survey from n = 41 organizations involved in the Health Improvement Partnership of Maricopa County (HIPMC), in Arizona. Using the previously validated Program to Analyze, Record, and Track Networks to Enhance Relationships (PARTNER) tool, organizations provided information on existing ties with other coalition members, including frequency and depth of partnership and eight categories of perceived value/trust of each current partner organization. RESULTS: The coalition's overall network had a density score of 30 %, degree centralization score of 73 %, and trust score of 81 %. Network maps are presented to identify existing relationships between HIPMC members according to partnership frequency and intensity, duration of involvement in the coalition, and self reported contributions to the coalition. Overall, number of ties and other partnership measures were positively correlated with an organization's perceived value and trustworthiness as rated by other coalition members. CONCLUSIONS: Our study presents a novel use of social network analysis methods to evaluate the coalition of organizations involved in implementing a CHIP in an urban community. The large coalition had relatively low network density but high degree centralization-meaning key organizations link organizations otherwise not tightly partnering. Coalition members rated each other highly on trust, a positive sign for future partnership development efforts. Examination of network maps reveal key organizations that can be targeted for future partnership facilitation and expansion. Future network data collection will enable exploration of longitudinal trends and exploration of network characteristics versus health behavior, status, and outcome changes. PMID- 27411473 TI - The overexpression of p16 is not a surrogate marker for high-risk human papilloma virus genotypes and predicts clinical outcomes for vulvar cancer. AB - BACKGROUND: We aimed to evaluate the correlation between p16(ink4a) overexpression and high risk (hr)HPV-DNA in vulvar squamous cell carcinoma (vSCC) tumors as well as the impact of both biomarkers on the prognosis of vSCC patients. METHODS: PCR-detection of (hr)HPV-DNA and immunohistochemical staining for p16(ink4a) were conducted in 85 vSCC tumors. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: p16(ink4a)-overexpression and (hr)HPV-DNA were detected in 35 and 37 of the 85 tumors, respectively. Among the 35 p16(ink4a)-positive tumors, 10 lacked (hr)HPV DNA (29 %). Among the 50 p16(ink4a)-negative tumors, (hr)HPV-DNA was detected in 12 cases (24 %). The median follow-up was 89.20 months (range 1.7-189.5 months). P16(ink4a)-overexpression, but not (hr)HPV-DNA positivity of the primary tumor, was correlated with prolonged overall survival (OS) (p = 0.009). P16(ink4a) overexpression predicted a better response to radiotherapy (p < 0.001). Univariate analysis has demonstrated that age (p = 0.025), tumor grade (p = 0.001), lymph node metastasis (p < 0.001), FIGO stage (p < 0.001), p16(ink4a) overexpression (p = 0.022), and adjuvant RTX (p < 0.001) were prognostic factors for OS. Multivariate analysis has demonstrated that lymph node metastasis (HR 1 2.74, 95 % CI 1.50-5.02, p = 0.019), tumor grade (HR 1-2.80, 95 % CI 1.33-5.90, p = 0.007) and p16(ink4a)-overexpression (HR 1-2.11, 95 % CI 1.13-3.95, p = 0.001) are independent prognostic factors. CONCLUSION: The discovered overlap suggests the use of p16(ink4a) in combination with HPV-DNA detection as an ancillary test for future research and clinical studies in vSCC. The prognostic and predictive value of p16(ink4a)-overexpression should be tested in larger cohort studies. PMID- 27411476 TI - Penetratin Peptide-Functionalized Gold Nanostars: Enhanced BBB Permeability and NIR Photothermal Treatment of Alzheimer's Disease Using Ultralow Irradiance. AB - The structural changes of amyloid-beta (Abeta) from nontoxic monomers into neurotoxic aggregates are implicated with pathogenesis of Alzheimer's disease (AD). Over the past decades, weak disaggregation ability and low permeability to the blood-brain barrier (BBB) may be the main obstacles for major Abeta aggregation blockers. Here, we synthesized penetratin (Pen) peptide loaded poly(ethylene glycol) (PEG)-stabilized gold nanostars (AuNS) modified with ruthenium complex (Ru@Pen@PEG-AuNS), and Ru(II) complex as luminescent probes for tracking drug delivery. We revealed that Ru@Pen@PEG-AuNS could obviously inhibit the formation of Abeta fibrils as well as dissociate preformed fibrous Abeta under the irradiation of near-infrared (NIR) due to the NIR absorption characteristic of AuNS. More importantly, this novel design could be applied in medicine as an appropriate nanovehicle, being highly biocompatible and hemocompatible. In addition, Ru@Pen@PEG-AuNS had excellent neuroprotective effect on the Abeta-induced cellular toxicity by applying NIR irradiation. Meanwhile, Pen peptide could effectively improve the delivery of nanoparticles to the brain in vitro and in vivo, which overcame the major limitation of Abeta aggregation blockers. These consequences illustrated that the enhanced BBB permeability and efficient photothermolysis of Ru@Pen@PEG-AuNS are promising agents in AD therapy. PMID- 27411477 TI - Mechanism and analyses for extracting photosynthetic electrons using exogenous quinones - what makes a good extraction pathway? AB - Plants or algae take many benefits from oxygenic photosynthesis by converting solar energy into chemical energy through the synthesis of carbohydrates from carbon dioxide and water. However, the overall yield of this process is rather low (about 4% of the total energy available from sunlight is converted into chemical energy). This is the principal reason why recently many studies have been devoted to extraction of photosynthetic electrons in order to produce a sustainable electric current. Practically, the electron transfer occurs between the photosynthetic organism and an electrode and can be assisted by an exogenous mediator, mainly a quinone. In this regard, we recently reported on a method involving fluorescence measurements to estimate the ability of different quinones to extract photosynthetic electrons from a mutant of Chlamydomonas reinhardtii. In the present work, we used the same kind of methodology to establish a zone diagram for predicting the most suitable experimental conditions to extract photoelectrons from intact algae (quinone concentration and light intensity) as a function of the purpose of the study. This will provide further insights into the extraction mechanism of photosynthetic electrons using exogenous quinones. Indeed fluorescence measurements allowed us to model the capacity of photosynthetic algae to donate electrons to an exogenous quinone by considering a numerical parameter called "open center ratio" which is related to the Photosystem II acceptor redox state. Then, using it as a proxy for investigating the extraction of photosynthetic electrons by means of an exogenous quinone, 2,6-DCBQ, we suggested an extraction mechanism that was globally found consistent with the experimentally extracted parameters. PMID- 27411478 TI - Lack of scintigraphic response of fibrous dysplasia to bisphosphonate treatment. PMID- 27411479 TI - Heat shock proteins and their immunomodulatory role in inflammatory arthritis. AB - Autoimmune diseases, including inflammatory arthritis, are characterized by a loss of self-tolerance, leading to an excessive immune responses and subsequent ongoing inflammation. Current therapies are focused on dampening this inflammation, but a permanent state of tolerance is seldom achieved. Therefore, novel therapies that restore and maintain tolerance are needed. Tregs could be a potential target to achieve permanent immunotolerance. Activation of Tregs can be accomplished when they recognize and bind their specific antigens. HSPs are proteins present in all cells and are upregulated during inflammation. These proteins are immunogenic and can be recognized by Tregs. Several studies in animal models and in human clinical trials have shown the immunoregulatory effects of HSPs and their protective effects in inflammatory arthritis. In this review, an overview is presented of the immunomodulatory effects of several members of the HSP family in general and in inflammatory arthritis. These effects can be attributed to the activation of Tregs through cellular interactions within the immune system. The effect of HSP-specific therapies in patients with inflammatory arthritis should be explored further, especially with regard to long term efficacy and safety and their use in combination with current therapeutic approaches. PMID- 27411480 TI - MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis. AB - OBJECTIVE: To test the hypothesis that miR-155 regulates monocyte migratory potential via modulation of chemokine and chemokine receptor expression in RA, and thereby is associated with disease activity. METHODS: The miR-155 copy numbers in monocytes from peripheral blood (PB) of healthy (n = 22), RA (n = 24) and RA SF (n = 11) were assessed by real time-PCR using synthetic miR-155 as a quantitative standard. To evaluate the functional impact of miR-155, human monocytes were transfected with control or miR-155 mimic, and the effect on transcript levels, and production of chemokines was evaluated by Taqman low density arrays and multiplex assays. A comparative study evaluated constitutive chemokine receptor expression in miR-155-/- and wild-type murine (CD115 + Ly6C + Ly6G-) monocytes. RESULTS: Compared with healthy monocytes, the miR-155 copy number was higher in RA, peripheral blood (PB) and SF monocytes (PB P < 0.01, and SF P < 0.0001). The miR-155 copy-number in RA PB monocytes was higher in ACPA positive compared with ACPA-negative patients (P = 0.033) and correlated (95% CI) with DAS28 (ESR), R = 0.728 (0.460, 0.874), and with tender, R = 0.631 (0.306, 0.824) and swollen, R = 0.503 (0.125, 0.753) joint counts. Enforced-expression of miR-155 in RA monocytes stimulated the production of CCL3, CCL4, CCL5 and CCL8; upregulated CCR7 expression; and downregulated CCR2. Conversely, miR155-/- monocytes showed downregulated CCR7 and upregulated CCR2 expression. CONCLUSION: Given the observed correlations with disease activity, these data provide strong evidence that miR-155 can contribute to RA pathogenesis by regulating chemokine production and pro-inflammatory chemokine receptor expression, thereby promoting inflammatory cell recruitment and retention in the RA synovium. PMID- 27411481 TI - Low heme oxygenase-1 levels in patients with systemic sclerosis are associated with an altered Toll-like receptor response: another role for CXCL4? AB - OBJECTIVE: SSc is a disease characterized by inflammation and fibrosis. Heme Oxygenase-1 (HO-1) is a haem-degrading enzyme that mediates resolution of inflammation and is induced upon mediators abundantly present in SSc. We aimed to assess whether HO-1 expression/function is disturbed in SSc patients and could therefore be contributing to the ongoing inflammation. METHODS: In total, 92 SSc patients and 48 healthy controls were included. By measuring total bilirubin in plasma in vivo, HO-activity was assessed. HO-1 expression levels were determined with western blot in monocytes before and after induction of HO-1 with cobalt protoporphyrin (CoPP) with or without CXCL4. Monocyte-derived dendritic cells (DCs) were stimulated with several Toll-like receptor (TLR) ligands with or without pre-stimulation with CoPP for 24 h. Cytokine levels were measured in the supernatants using the Luminex Bead Array. RESULTS: SSc patients have lower plasma levels of bilirubin, suggestive of an aberrant HO-1 function. We demonstrated low HO-1 expression in immune cells from SSc patients, whereas induction with CoPP was able to restore HO-1 levels in DCs from SSc patients, almost normalizing the increased TLR response observed in SSc. Co-exposure to CXCL4 completely abrogated CoPP-induced HO-1 expression, suggesting that the high CXCL4 levels present in SSc patients block the normal induction of HO-1 and its function. CONCLUSION: We demonstrate that HO activity in SSc patients is decreased and show its functional consequences. Since CXCL4 blocks the induction of HO-1 expression, neutralization of CXCL4 in SSc patients could have clinical benefits by diminishing overactivation of immune cells and other anti inflammatory effects of HO-1. PMID- 27411482 TI - Partial remission in ankylosing spondylitis and non-radiographic axial spondyloarthritis in treatment with infliximab plus naproxen or naproxen alone: associations between partial remission and baseline disease characteristics. AB - OBJECTIVES: To evaluate partial remission during treatment with infliximab (IFX) + naproxen (NPX) vs NPX alone in patients from the two subgroups of SpA and explore baseline predictors of partial remission. METHODS: Infliximab as First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial was a double-blind, randomised controlled trial of IFX in biologic-naive patients with early, active axial SpA. Patients were randomised (2:1) to receive 28 weeks of treatment with i.v. IFX 5 mg/kg (weeks 0, 2, 6, 12, 18 and 24) + NPX 1000 mg/day or i.v. placebo (PBO) + NPX 1000 mg/day. The current post hoc analysis evaluated outcomes in patients who did or did not meet modified New York radiographic criteria for AS. RESULTS: The analysis included 94 patients who met AS criteria and 56 with non-radiographic axial SpA (nr-axSpA). At week 28, Assessment of SpondyloArthritis international Society (ASAS) partial remission was greater with IFX + NPX than PBO + NPX for both the AS group (70.5 vs 33.3%, respectively) and the nr-axSpA group (50.0 vs 37.5%, respectively). A similar pattern occurred with several efficacy measures. Larger treatment effects occurred in the AS group than the nr-axSpA group, possibly due to baseline differences in disease characteristics. Multivariable analyses identified the type of treatment, age and HLA-B27 status as predictors of ASAS partial remission in the total study population. MRI sacroiliac joint scores were associated with partial remission during IFX + NPX treatment. CONCLUSION: Patients with AS had greater partial remission with IFX + NSAID than NSAID therapy alone; patients with nr-axSpA had a smaller treatment effect. Baseline disease characteristics and age were associated with partial remission with IFX therapy. PMID- 27411483 TI - Electrons initiate efficient formation of hydroperoxides from cysteine. AB - Amino acid and protein hydroperoxides can constitute a significant hazard if formed in vivo. It has been suggested that cysteine can form hydroperoxides after intramolecular hydrogen transfer to the commonly produced cysteine sulfur centered radical. The resultant cysteine-derived carbon-centered radicals can react with oxygen at almost diffusion-controlled rate, forming peroxyl radicals which can oxidize other molecules and be reduced to hydroperoxides in the process. No cysteine hydroperoxides have been found so far. In this study, dilute air-saturated cysteine solutions were exposed to radicals generated by ionizing radiation and the hydroperoxides measured by an iodide assay. Of the three primary radicals present, the hydroxyl, hydrogen atoms and hydrated electrons, the first two were ineffective. However, electrons did initiate the generation of hydroperoxides by removing the -SH group and forming cysteine-derived carbon radicals. Under optimal conditions, 100% of the electrons reacting with cysteine produced the hydroperoxides with a 1:1 stoichiometry. Maximum hydroperoxide yields were at pH 5.5, with fairly rapid decline under more acid or alkaline conditions. The hydroperoxides were stable between pH 3 and 7.5, and decomposed in alkaline solutions. The results suggest that formation of cysteine hydroperoxides initiated by electrons is an unlikely event under physiological conditions. PMID- 27411484 TI - Structure and efficient luminescence upconversion of Ln(iii) aromatic N-oxide coordination polymers. AB - A series of lanthanide-based coordination polymers {[Yb1-xErx(4,4' bpdo)3(H2O)2](CF3SO3)3}infinity were synthesised by solvent diffusion techniques, where 4,4'-bpdo = 4,4'-bipyridine-N,N'-dioxide, and using differing mole fractions of Yb(iii) and Er(iii) which were systematically varied (x = 0, 0.05, 0.20, 0.50 and 1). All of the materials obtained were characterised using elemental analyses, single-crystal X-ray diffraction (SXRD) and solid-state photoluminescence studies. Structurally, the coordination polymers crystallise as an isomorphous series of infinite 2D sheets, which contain two inner sphere water molecules, and are isostructural with a previously characterised homometallic Yb(iii) compound. In addition to the normal Near Infra-Red (NIR) luminescence, these compounds also demonstrate upconversion emission upon 980 nm excitation. Upconversion luminescence measurements reveal visible emission in the red, green, and blue regions corresponding to the (2)H11/2->(4)I15/2, (4)F9/2->(4)I15/2 and (2)H9/2->(4)I15/2 transitions of the Er(iii) cation upon two and three-photon excitation. We also observed weak emission from the Er(iii) cation in the UV region for the first time in a Ln-MOF based material. PMID- 27411485 TI - Nanoparticles for Cancer Targeting: Current and Future Directions. AB - The targeting of pharmaceuticals is a rapidly evolving strategy to overcome the difficulties in therapeutic delivery, especially to the tumor site. Unlike traditional drug delivery systems, nanoparticles based compounds attain superior accretion in the tumor site by their active or passive mechanisms. Due to their exclusive properties like small size, large surface-to-volume ratio, tunable surface chemistry, and the ability to encapsulate various drugs, the nano-sized carriers provide longer circulation time; easy penetration into cellular membranes; efficient site-specific targeting. Recent advancements in polymeric- nanomedicines involve targeting of polymer-based nanoparticles (NPs), micelles, polyplexes, dendrimers, polymersomes, drug/protein conjugates and lipid hybrid systems to tumor pathological site. With different functional moieties, NPs improve the performance in terms of targetability, circulation longevity, enhanced intracellular penetration, stimuli-sensitivity, and carrier-mediated visualization. This review highlighted different preparative techniques and types of nanoparticles in the most recent developments in cancer treatment including promising opportunities in targeted; combination therapy; and other medical and biomedical applications. Various delivery strategies and future prospects of nanoparticles are also enlisted. Apart from that, the review discusses the potential advances and targeting of polymeric nanocarriers within the scope of cancer therapeutic system to emphasize it as an auxiliary tool to the customary drug delivery systems. PMID- 27411486 TI - Correction: Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma. PMID- 27411487 TI - A composite light-harvesting layer from photoactive polymer and halide perovskite for planar heterojunction solar cells. AB - A new route for fabrication of photoactive materials in organic-inorganic hybrid solar cells is presented in this report. Photoactive materials by blending a semiconductive conjugated polymer with an organolead halide perovskite were fabricated for the first time. The composite active layer was then used to make planar heterojunction solar cells with the PCBM film as the electron-acceptor. Photovoltaic performance of solar cells was investigated by J-V curves and external quantum efficiency spectra. We demonstrated that the incorporation of the conjugated photoactive polymer into organolead halide perovskites did not only contribute to the generation of charges, but also enhance stability of solar cells by providing a barrier protection to halide perovskites. It is expected that versatile of conjugated semi-conductive polymers and halide perovskites in photoactive properties enables to create various combinations, forming composites with advantages offered by both types of photoactive materials. PMID- 27411488 TI - Differences in prognosis of stereotyped IGHV3-21 chronic lymphocytic leukaemia according to additional molecular and cytogenetic aberrations. PMID- 27411489 TI - Erratum to: SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm. PMID- 27411490 TI - CD47 Promotes Tumor Invasion and Metastasis in Non-small Cell Lung Cancer. AB - CD47 is overexpressed in many human cancers, its level positively correlates with tumor invasion and metastasis. However, it is largely unknown whether CD47 overexpression drives metastasis and how CD47 lead to tumor metastasis in non small cell lung cancer (NSCLC). In this study, we analyzed NSCLC specimens and cell lines, and revealed that CD47 is expressed at a higher level than in tumor free control samples. Furthermore, increased CD47 expression correlated with clinical staging, lymph node metastasis and distant metastasis. In order to understand the molecular mechanisms underlying CD47 functions, we applied both gain-of-function and loss-of-function approaches in cell lines. The siRNA mediated downregulation of CD47 inhibited cell invasion and metastasis in vitro, while the overexpression of CD47 by plasmid transfection generated opposite effects. In vivo, CD47-specific shRNA significantly reduced tumor growth and metastasis. On the molecular level, the expression of CD47 correlated with that of Cdc42, both in cell lines and NSCLC specimens. The inhibition of Cdc42 attenuates the invasion and metastasis of CD47-overexpressing cells. These results indicate that Cdc42 is a downstream mediator of CD47-promoted metastasis. Our findings provide first evidence that CD47 is an adverse prognostic factor for disease progression and metastasis, and a promising therapeutic target for NSCLC. PMID- 27411491 TI - Prevalence and determinants of preconception folic acid use: an Italian multicenter survey. AB - BACKGROUND: Women in many countries are advised to use folic acid supplements before and early during pregnancy to reduce the risk of neural tube defects in their infants. This study aimed to update the prevalence and to identify possible determinants of preconception folic acid supplement use in Italian women. METHODS: The study was based on cross-sectional data from seven maternity clinics located in six Italian regions from January to June, 2012. Data on maternal characteristics and supplement use were collected for 2,189 women using a self administered questionnaire. RESULTS: Preconception folic acid use was reported by 23.5 % (n = 515) of the participants. Of these, 479 (93 %) women had taken folic acid supplements on a daily basis as recommended by the health authorities. Women who both had intended their pregnancy and had requested a preconception health visit to a doctor/gynecologist were substantially more likely than the reference group to initiate folic acid supplementation before their pregnancy (48.6 versus 4.8 %). Preconception folic acid use was also associated with higher maternal age, higher education, marriage/cohabitation, lower parity, infertility treatments, and chronic disease. CONCLUSIONS: Data from seven maternity clinics located in six Italian regions indicate that preconception folic acid supplement use in many Italian women is low. Women who do not plan their pregnancy or do not request a preconception health visit to their doctor have among the lowest prevalence of preconception folic acid use. Improving folate status in these and other supplemental non-users may have important disease preventive effects. PMID- 27411492 TI - Corrigendum. PMID- 27411495 TI - Disk to dual ring deposition transformation in evaporating nanofluid droplets from substrate cooling to heating. AB - Substrate temperature plays an important role in deposited morphologies formed after the evaporation of nanofluid droplets. The deposited patterns are shown to vary from a uniform disk-like profile to a dual ring from cooling to heating of the substrate. The droplet on the substrate with a relatively low temperature reveals three primary stages. Stage I features an outward transport of nanoparticles along the liquid-air interface near the droplet edge. Meanwhile some nanoparticles form sediment on the solid surface with a certain distance to the contact line. In the central region nanoparticles are dominated by Brownian motion so they fluctuate around their positions. Stage II is characterized by an increasing outward transport of nanoparticles in the bulk so the coffee ring is gradually enhanced. Most particles in Stages I and II are central-concentrated, leaving an annular gap sparsely covered adjacent to the outer ring. In Stage III, the pattern is homogenized by filling the gap with the arrival of the interior nanoparticles. Upon increasing the substrate temperature, the accompanied flow pattern exhibits a transition when the substrate still remains cooler than the atmosphere. It is resulted from the evaporative cooling at the droplet apex counteractive to the applied temperature gradient by substrate cooling. Above the transition temperature, the induced inward Marangoni flow takes place earlier at a higher substrate temperature, and in conjunction with the outward radial flow a dual ring pattern is formed. PMID- 27411493 TI - Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function. AB - Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 MUg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468; 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects. PMID- 27411494 TI - Pre-hospital delay and its associated factors in first-ever stroke registered in communities from three cities in China. AB - This study aimed to explore pre-hospital delay and its associated factors in first-ever stroke registered in communities from three cities in China. The rates of delay greater than or equal to 2 hours were calculated and factors associated with delays were determined by non-conditional binary logistic regression, after adjusting for different explanatory factors. Among the 403 cases of stroke with an accurate documented time of prehospital delay, the median time (interquartile range) was 4.00 (1.50-14.00) hours. Among the 544 cases of stroke with an estimated time range of prehospital delay, 24.8% of patients were transferred to the emergency department or hospital within 2 hours, only 16.9% of patients with stroke were aware that the initial symptom represented a stroke, only 18.8% used the emergency medical service and one-third of the stroke cases were not identified by ambulance doctors. In the multivariate analyses, 8 variables or sub variables were identified. In conclusion, prehospital delay of stroke was common in communities. Thus, intervention measures in communities should focus on education about the early identification of stroke and appropriate emergency medical service (EMS) use, as well as the development of organized stroke care. PMID- 27411496 TI - Practice eligible route for certification in geriatric psychiatry: why some Canadian psychiatrists are disinterested in writing the RCPSC subspeciality examination? AB - Geriatric psychiatry was officially recognized as a subspecialty by the Royal College of Physicians and Surgeons of Canada (RCPSC) in 2009, with the first RCPSC exam written in 2013 (Andrew and Shea, 2010). The unique mental health needs of Canadians' seniors requires geriatric psychiatrists trained to address them (Herrmann, 2004), but current rates of recruitment in informal fellowship programs have been inadequate (Bragg et al., 2012). One hope of subspeciality recognition was to increase recruitment in Canada, but there have been some challenges in accrediting psychiatrists already caring for older adults. Many currently practicing geriatric psychiatrists have elected to take the Royal College examination, with >120 graduates in the first year, 2013, but others have been more ambivalent. In this letter, we perform a preliminary exploration of the prevalence and correlates of disinterest in completing the RCPSC geriatric psychiatry examination. PMID- 27411497 TI - Feasibility and acceptability of a mobile app in an ecological momentary assessment of early breastfeeding. AB - Ecological momentary assessment (EMA) is a novel data collection method that samples subject experiences in real-time - minimizing recall bias. Here, we describe the feasibility of EMA to track breastfeeding behaviour through a mobile phone app. During their birth hospitalization, we approached healthy, first-time mothers intending to exclusively breastfeed for at least 2 months to participate in a study tracking breastfeeding through 8 weeks postpartum. Participants downloaded a commercially available smartphone app, entered information and thoughts about breastfeeding as they occurred, and emailed this data weekly. We called participants at 2 and 8 weeks to assess breastfeeding status. At the 8 week call, we also assessed participants' experiences using the app. Of the 61 participants, 38% sent complete or nearly complete feeding data, 24% sent some data, and 38% sent no data; 58% completed at least one free-text breastfeeding entry, and five women logged daily or near daily entries. Compared with women who sent no data, those who sent any were more likely to be married, highly educated, intend to breastfeed more than 6 months, have a more favourable baseline attitude towards breastfeeding, and less likely to have used formula during hospitalization. There was a high degree of agreement between participant reported proportion of breast milk feeds via app and interview data at 2 weeks (ICC 0.97). Experiences with the app ranged from helpful to too time-consuming or anxiety-provoking. Participants and researchers encountered technical issues related to app use and analysis, respectively. While our data do not support the feasibility of stand-alone app-based EMA to track breastfeeding behaviour, it may provide rich accounts of the breastfeeding experience for certain subgroups of women. (c) 2016 John Wiley & Sons Ltd. PMID- 27411498 TI - Visible-light-driven selective oxidation of benzyl alcohol and thioanisole by molecular ruthenium catalyst modified hematite. AB - Molecular ruthenium catalysts were found to selectively catalyze the oxidation of thioanisole to sulfoxide with a yield up to 100% in the presence of visible light and sacrificial reagents when they were anchored onto hematite powder. The composite photocatalysts also showed about 5 times higher efficiencies in benzyl alcohol oxidation than the system composed of dispersed molecular catalysts and hematite particles in aqueous solution. A photoelectrochemical cell based on a molecular catalyst modified hematite photoanode was further fabricated, which exhibited high activity towards the oxidation of organic substrates. PMID- 27411499 TI - Neural correlates of maintaining generated images in visual working memory. AB - How are images that have been assembled from their constituting elements maintained as a coherent representation in visual working memory (vWM)? Here, we compared two conditions of vWM maintenance that only differed in how vWM contents had been created. Participants maintained images that they either had to assemble from single features or that they had perceived as complete objects. Object complexity varied between two and four features. We analyzed electroencephalogram phase coupling as a measure of cortical connectivity in a time interval immediately before a probe stimulus appeared. We assumed that during this time both groups maintained essentially the same images, but that images constructed from their elements would require more neural coupling than images based on a complete percept. Increased coupling between frontal and parietal-to-occipital cortical sources was found for the maintenance of constructed in comparison to nonconstructed objects in the theta, alpha, beta, and gamma frequency bands. A similar pattern was found for an increase in vWM load (2 vs. 4 features) for nonconstructed objects. Under increased construction load (2 vs. 4 features for constructed images), the pattern was restricted to fronto-parietal couplings, suggesting that the fronto-parietal attention network is coping with the higher attentional demands involved in maintaining constructed images, but without increasing the communication with the occipital visual buffer in which the visual representations are assumed to be stored. We conclude from these findings that the maintenance of constructed images in vWM requires additional attentional processes to keep object elements together as a coherent representation. Hum Brain Mapp 37:4349-4362, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27411500 TI - Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord. AB - BACKGROUND: For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. METHODS: Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. RESULTS: Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naive animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. CONCLUSIONS: Intrathecal PA exerts anti allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord. PMID- 27411501 TI - Neuropsychiatric symptoms in dementia may predict caregiver burden: a Sicilian exploratory study. AB - BACKGROUND: Behavioural and psychological symptoms of dementia are very common. They represent a main cause of burden and distress in caregivers and can lead to early institutionalization of patients. We aimed to find the most specific behavioural and psychological symptoms of dementia that can strongly affect the caregivers' burden. METHODS: Twenty-seven patients and their caregivers were enrolled in this study. All of the patients were affected by Alzheimer's, vascular, or frontotemporal dementia and were evaluated with the Neuropsychiatric Inventory and Mini-Mental State Examination. Caregivers were administered the Caregiver Burden Inventory. RESULTS: Apathy, depression, anxiety, and agitation were the most common symptoms and were found in up to 90% of the patients. We detected strong correlations between patient neuropsychiatric symptoms, (i.e. irritability, hallucinations, aberrant motor behavioural, depression, and agitation) and Caregiver Burden Inventory scores. Multiple regression analysis found hallucinations, irritability, and depression to be significant predictors of caregiver burden. Moreover, the Neuropsychiatric Inventory score was more closely related to caregiver burden than the Mini-Mental State Examination score. CONCLUSION: Our results revealed that demented patients' behavioural problems are related to the level of caregiver burden and distress. Further investigations are needed to differentiate the present findings among dementia subtypes and to better evaluate the effect of caregivers' personal characteristics on their own burden. PMID- 27411502 TI - A study on paracetamol cardiotoxicity. AB - BACKGROUND: Sri Lanka has a high suicide rate, with more than 40 % of poisoning admissions due to overdose of drugs with Paracetamol being the commonest. Data regarding cardiotoxicity to paracetamol is very minimal though hepatotoxicity following poisoning is well studied. Paracetamol cardiotoxicity has rarely been clinically significant and may have well been overlooked. The possibility that paracetamol overdose might be directly cardiotoxic has been the subject of a few reports. Unexplained deaths and electrocardiographic changes associated with paracetamol poisoning have also been reported in which cardiac origin cannot be clearly ruled out. Although some studies state that paracetamol poisoning has no direct cardiotoxic effect, electrocardiographic changes due to metabolic derangement of hepatotoxicity have been shown in certain studies. Thus, we conducted this study to assess in detail the cardiotoxic effect of paracetamol poisoning. METHODS: This is a cross sectional descriptive study done on those with confirmed paracetamol poisoning. Serum paracetamol levels, Electrocardiogram, Echocardiogram, troponin I, and other basic investigations were done. RESULTS: Paracetamol ingestion is more common among teenagers and the young population in Sri Lanka. Although several cases of paracetamol poisoning induced cardiotoxicity has been described in the past, this study demonstrated no electrocardiographic, echocardiographic or cardiac biomarkers changes of myocardial toxicity. CONCLUSION: Though literature review support cardiotoxicity following paracetamol poisoning, our study does not provide enough evidence for this. Continuous cardiac monitoring, serial troponin and echocaediogram assessment would be voluble adjunct in its management. Further experiments and research in this subject would be useful with a larger number of samples to further evaluate this important problem. PMID- 27411503 TI - Possible mechanisms of the crosstalk between Langerhans cells and regulatory T cells in extramammary Paget disease by receptor activator of nuclear factor kappa B (RANK) ligand/RANK pathways. AB - BACKGROUND: Extramammary Paget disease (EMPD) is a skin adenocarcinoma of apocrine gland origin, in which Paget cells express receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) and matrix metalloproteinase (MMP)-7, and release soluble (s)RANKL into the tumour microenvironment. We previously reported that about 60% of the RANK+ cells among the stromal cells are M2 macrophages, but the identity of the remaining population of RANK+ cells is still unknown. OBJECTIVES: To investigate the unknown subpopulation of RANK-expressing cells in EMPD. METHODS: The main population of RANK-expressing cells in the epidermis was composed of epidermal Langerhans cells (LCs). To explore the effects of RANKL on LCs, we stimulated LCs generated from human CD34+ hematopoietic progenitor cells with graded concentrations of sRANKL. To further examine the correlation between LCs and regulatory T cells (Tregs) in EMPD, we employed immunohistochemical staining. RESULTS: sRANKL stimulation was shown to augment the production of C-C motif chemokine ligand 17 (CCL17) from LCs. We additionally demonstrated CCL17 expression by CD1a+ LCs in EMPD in an immunofluorescence study. Spearman's rank correlation test confirmed a correlation between the number of LCs and the number of Foxp3+ Tregs in the lesional skin of invasive EMPD. In addition, the numbers of Foxp3+ Tregs in the sentinel lymph nodes of metastatic EMPD were significantly higher than those of metastatic melanoma, which did not express RANKL. CONCLUSIONS: The findings suggest that the RANKL/RANK pathway in EMPD might contribute to the recruitment of Tregs and to maintenance of the tumour microenvironment. PMID- 27411505 TI - Erratum to: Failed pneumoperitoneum for laparoscopic surgery following autologous Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: a case report. PMID- 27411504 TI - MicroRNA-181a-5p enhances cell proliferation in medullary thymic epithelial cells via regulating TGF-beta signaling. AB - The expression profiles of miRNAs in thymus tissues from mice of different age have been demonstrated in our previous study. After an integrated analysis of the miRNA expression profiles, we demonstrated that the expression of miR-181a-5p was significantly decreased in thymic epithelial cells (TECs) from 10- to 19-month old mice when compared with that in TECs from 1-month-old mice by quantitative reverse transcriptase polymerase chain reaction. We hypothesized that miR-181a-5p in TECs might be associated with the age-related thymus involution through regulating some genes or signaling pathway. To test this hypothesis, the mouse medullary thymic epithelial cells (MTEC1) were used. Transfection with miR-181a 5p mimic promoted the proliferation of MTEC1 cells, but did not affect apoptosis. The effect was reversed when the expression of miR-181a-5p was suppressed in MTEC1 cells. Furthermore, the transforming growth factor beta receptor I (Tgfbr1) was confirmed as a direct target of miR-181a-5p by luciferase assay. Moreover, it was found that overexpression of miR-181a-5p down-regulated the phosphorylation of Smad3 and blocked the activation of the transforming growth factor beta signaling. Nevertheless, an inversely correlation was observed between the expression of Tgfbr1 and miR-181a-5p in TECs derived from mice of different age. Collectively, we provide evidence that miR-181a-5p may be an important endogenous regulator in the proliferation of TECs, and the expression levels of miR-181a-5p in TECs may be associated with the age-related thymus involution. PMID- 27411506 TI - Erratum to: 'Genomic structure and marker-derived gene networks for growth and meat quality traits of Brazilian Nelore beef cattle'. PMID- 27411507 TI - Heparin-induced thrombocytopenia in cardiac surgery and critically ill patients. AB - Thrombocytopenia as well as anti-platelet factor 4/heparin (PF4/H) antibodies are common in cardiac surgery patients and those treated in the intensive care unit. In contrast, heparin-induced thrombocytopenia (HIT) is uncommon in these populations (~1 % and ~0.5 %, respectively). A stepwise approach where testing for anti-PF4/H antibodies is performed only in patients with typical clinical symptoms of HIT improves diagnostic specificity of the laboratory assays without losing sensitivity, thereby helping to avoid overdiagnosis and resulting HIT overtreatment. Short-term re-exposure to heparin, especially given intraoperatively for cardiovascular surgery, is a reasonable therapeutic option in patients with a history of HIT who subsequently test negative for HIT antibodies. Organ failure(s), enhanced bleeding risks, and other characteristics require special considerations regarding non-heparin anticoagulation: Argatroban is the alternative anticoagulant with pharmacokinetics independent of renal function, but it has a prolonged half-life in case of impaired liver function. For bivalirudin, protocols during cardiopulmonary bypass surgery are established, and it is suitable for patients with liver insufficiency. A major issue of direct thrombin inhibitors are false high activated partial thromboplastin time values in patients with comorbidities affecting prothrombin, which can result in systematic underdosing of the drugs. This is not the case for danaparoid and fondaparinux, which can be monitored by anti-factor Xa assays, but have long half lives and no suitable antidote. This review includes also information on management of on- and off-pump cardiac surgery, ventricular assist devices, percutaneous interventions, continuous renal replacement therapy, and extracorporeal membrane oxygenation in patients with HIT. PMID- 27411509 TI - Diagnosis of Giardia duodenalis Infection using Dot Blot in Comparison with Microscopy. AB - BACKGROUND AND PURPOSE: Giardia duodenalis is an intestinal flagellate parasite which spreads all over the world and is considered as a health problem in the most rural and low sanitation areas. Many diagnostic tests have been developed for the detection of Giardia parasite in stool samples but all of them have some disadvantages such as lack of sensitivity and specificity. In search for a simple and accurate test, diagnosis of Giardia infection using dot blot method has been investigated in this work. MATERIALS AND METHODS: In this descriptive study, 30 stool samples which their infection with Giardia were confirmed by direct examination and formalin ether considered as case group. Thirty stool samples without Giardia infection according to formalin ether examination were also considered as a control group. Giardia cysts were isolated from the stool samples using sucrose method. In order to raise antiserum against Giardia cysts, the purified cysts were then sonicated and injected to a rabbit. A mono specific antiserum against the 66KDa band of Giardia cyst antigen was also prepared. The two antisera were used in the dot blot test. Finally, the sensitivity and specificity of the dot-blot method were estimated by considering formalin ether as the gold standard. RESULTS: When Poly specific antiserum was used, the sensitivity and specificity of the dot blot for detection of Giardia infection were 77% and 64% respectively. However the sensitivity and specificity of this assay were 97% and 64% respectively when monospecific antiserum was used. CONCLUSION: It seems that dot blot is an easy method for the diagnosis of Giardia especially in the rural areas. However more work is recommended for further development of this test. PMID- 27411508 TI - Nocardia asteroides-Induced movement abnormalities in mice: Relevance for Parkinson's disease? PMID- 27411510 TI - ICQG 5 on Madison's Isthmus links genomics and statistics of complex traits. PMID- 27411511 TI - Kalle Maijala 1927-2016. PMID- 27411513 TI - Does nurses' health affect their intention to remain in their current position? AB - AIM: To investigate and describe nurses' and midwives' physical health, rates of symptoms and disease, and to determine if these factors contribute to intention to leave. BACKGROUND: The nursing and midwifery workforce is ageing yet little is known about their physical health or its relationship to intention to leave. METHODS: An online survey of health and work-related assessments was distributed through the New South Wales Nurses and Midwives Association and professional contacts. RESULTS: Nurses and midwives (n = 5041) reported good-very good health overall. With 22.2% intending to leave in the next 12 months, older age, better perceived health and job satisfaction, regional residence and not working shifts predicted no intention to leave while breathing problems predicted intention to leave. CONCLUSIONS: Study findings flag the importance of health as an influence on intention to leave. Alongside job satisfaction and shift-working, health presents opportunities for workplace initiatives to maintain nurses in the workforce. IMPLICATIONS FOR NURSING MANAGEMENT: Educators, managers and policy makers should heed the significant influence of health for retention of staff and consider what strategies may mitigate health risks for this workforce. PMID- 27411514 TI - Activation tagging in indica rice identifies ribosomal proteins as potential targets for manipulation of water-use efficiency and abiotic stress tolerance in plants. AB - We have generated 3900 enhancer-based activation-tagged plants, in addition to 1030 stable Dissociator-enhancer plants in a widely cultivated indica rice variety, BPT-5204. Of them, 3000 were screened for water-use efficiency (WUE) by analysing photosynthetic quantum efficiency and yield-related attributes under water-limiting conditions that identified 200 activation-tagged mutants, which were analysed for flanking sequences at the site of enhancer integration in the genome. We have further selected five plants with low Delta13 C, high quantum efficiency and increased plant yield compared with wild type for a detailed investigation. Expression studies of 18 genes in these mutants revealed that in four plants one of the three to four tagged genes became activated, while two genes were concurrently up-regulated in the fifth plant. Two genes coding for proteins involved in 60S ribosomal assembly, RPL6 and RPL23A, were among those that became activated by enhancers. Quantitative expression analysis of these two genes also corroborated the results on activating-tagging. The high up-regulation of RPL6 and RPL23A in various stress treatments and the presence of significant cis-regulatory elements in their promoter regions along with the high up regulation of several of RPL genes in various stress treatments indicate that they are potential targets for manipulating WUE/abiotic stress tolerance. PMID- 27411516 TI - Grin and Bear It?: Employees' Use of Surface Acting During Co-worker Conflict. AB - Using survey data from 459 employed individuals, the conditional indirect effects of three types of interpersonal conflict at work on strains and performance through surface acting were tested. Results indicated that task, relationship and non-task organizational conflict were positively related to depressive and physical symptoms and negatively related to performance. Task conflict had a significantly weaker association with employee outcomes than either relationship or non-task organizational conflict. Surface acting negatively related to all types of conflict, although it had a weaker association with relationship conflict than task or non-task organizational conflict. Support was found for moderated mediation relationships whereby surface acting mediated the associations between all types of conflict with depressive symptoms, as well as the association between relationship and non-task organizational conflict with physical symptoms, when conflict was infrequent. Surface acting also mediated the associations between all types of conflict and performance when conflict was frequent. Future research directions are discussed that can advance our theoretical understanding of how emotional labour and interpersonal conflict interact to affect employees, as well as further our ability to improve employee well-being and organizational functioning. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27411515 TI - ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity. AB - Irisin reportedly promotes the conversion of preadipocytes into "brown-like" adipocytes within subcutaneous white adipose tissue (WAT) via a mechanism that stimulates UCP-1 expression. An increase in plasma irisin has been associated with improved obesity and insulin resistance in mice with type 2 diabetes. But whether a low level of irisin stimulates the development of obesity has not been determined. In studying mice with muscle-specific constitutive ROCK1 activation (mCaROCK1), we found that irisin production was down-regulated and the mice developed obesity and insulin resistance. Therefore, we studied the effects of irisin deficiency on energy metabolism in mCaROCK1 mice. Constitutively activation of ROCK1 in muscle suppressed irisin expression in muscle resulting in a low level of irisin in circulation. Irisin deficiency reduced heat production and decreased the expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) and subcutaneous WAT. Moreover, mCaROCK1 mice also displayed impaired glucose tolerance. Notably, irisin replenishment in mCaROCK1 mice partially reversed insulin resistance and obesity and these changes were associated with increased expression of UCP1 and Pref-1 in subcutaneous WAT. These results demonstrate that irisin mediates muscle-adipose tissue communication and regulates energy and glucose homeostasis. Irisin administration can correct obesity and insulin resistance in mice. PMID- 27411517 TI - SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2 in colorectal cancer. AB - BACKGROUND: To improve current treatment strategies for patients with aggressive colorectal cancer (CRC), the molecular understanding of subgroups of CRC with poor prognosis is of vast importance. SOX2 positive tumors have been associated with a poor patient outcome, but the functional role of SOX2 in CRC patient prognosis is still unclear. METHODS: An in vitro cell culture model expressing SOX2 was used to investigate the functional role of SOX2 in CRC. In vitro findings were verified using RNA from fresh frozen tumor tissue or immunohistochemistry on formalin fixed paraffin embedded (FFPE) tumor tissue from a cohort of 445 CRC patients. RESULTS: Using our in vitro model, we found that SOX2 expressing cells displayed several characteristics of cancer stem cells; such as a decreased proliferative rate, a spheroid growth pattern, and increased expression of stem cell markers CD24 and CD44. Cells expressing SOX2 also showed down-regulated expression of the intestinal epithelial marker CDX2. We next evaluated CDX2 expression in our patient cohort. CDX2 down-regulation was more often found in right sided tumors of high grade and high stage. Furthermore, a decreased expression of CDX2 was closely linked to MSI, CIMP-high as well as BRAF mutated tumors. A decreased expression of CDX2 was also, in a stepwise manner, strongly correlated to a poor patient prognosis. When looking at SOX2 expression in relation to CDX2, we found that SOX2 expressing tumors more often displayed a down-regulated expression of CDX2. In addition, SOX2 expressing tumors with a down-regulated CDX2 expression had a worse patient prognosis compared to those with retained CDX2 expression. CONCLUSIONS: Our results indicate that SOX2 expression induces a cellular stem cell state in human CRC with a decreased expression of CDX2. Furthermore, a down-regulated expression of CDX2 results in a poor patient prognosis in CRC and at least part of the prognostic importance of SOX2 is mediated through CDX2 down-regulation. PMID- 27411518 TI - Predictors of sun protection behaviours and sunburn among Australian adolescents. AB - BACKGROUND: Excessive sun exposure and sunburn increase individuals' risk of skin cancer. It is especially important to prevent sunburn in childhood due to the higher relative risk of skin cancer across the life span compared to risk associated with sunburn episodes experienced later in life. This study examined demographic and attitudinal factors associated with engagement in a range of sun protection behaviours (wearing a hat, wearing protective clothing, staying in the shade, and staying indoors during the middle of the day) and the frequency of sunburn among Western Australian adolescents to provide insights of relevance for future sun protection campaigns. METHODS: Cross-sectional telephone surveys were conducted annually with Western Australians between 2005/06 and 2014/15. The results from 4150 adolescents aged 14-17 years were used to conduct a path analysis of factors predicting various sun protection behaviours and sunburn. RESULTS: Significant primary predictors of the sun protection behaviours included in the study were skin type (sun sensitivity), gender, tanning-related attitudes and behaviours, and perceived relevance of public service advertisements that advocate sun protection. Of the four sun protection behaviours investigated, staying in the shade and staying indoors during the middle of the day were associated with a lower frequency of sunburn. CONCLUSION: There is a particular need to target sun protection messages at adolescent males who are less likely to engage in the most effective sun protection behaviours and demonstrate an increased propensity to experience sunburn. The results suggest that such future sun protection messages should include a focus on the importance of staying in the shade or indoors during periods of high UV radiation to increase awareness of the efficacy of these methods of avoiding skin cancer. PMID- 27411519 TI - Forgetful but not forgotten: Bathroom-related craniofacial trauma among the elderly. AB - OBJECTIVES/HYPOTHESIS: As our population ages, injuries attributable to falls continue to increase, impacting healthcare delivery. Evaluation of craniofacial trauma with focus on elderly patients remains an underappreciated concern. Our objectives were to evaluate injury trends associated with elderly bathroom falls, as this information may be useful for counseling and preventive purposes. STUDY DESIGN: Database review. METHODS: The National Electronic Injury Surveillance System was evaluated for craniofacial trauma among patients 60 years and older presenting to the emergency department (ED) (2010-2014). Injury descriptions were reviewed for mechanism of injury, patient demographics, and other injury characteristics. RESULTS: In total, 7.2% of the estimated 3.4 million ED visits for elderly craniofacial trauma were bathroom related. Females comprised the majority (60.9%) of patients, and a plurality of patients were in their 80s. A greater proportion of facial injuries resulted from syncope (16.6% vs. 10.9% compared to head injuries). Toilets facilitated a greater proportion of facial insults and were more likely to require admission; the most common mechanism was "falling off." Showers contributed a majority of head injuries and had a lower median age than toilet injuries. Fractures comprised 12.6% of facial injuries; of craniofacial fractures, common sites included the nose (54%), mandible (6%), and orbit (6%). Admitted patients were significantly older than those who were released. CONCLUSIONS: Bathroom falls result in a significant proportion of elderly traumatic injury. The trends we present offer the opportunity for targeted preventative measures to decrease the occurrence of these events. Additionally, this information may adjunct a detailed history and physical to ensure appropriate patient management. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:820 827, 2017. PMID- 27411520 TI - Valvular Disease: Role of cardiac surgery support during contemporary TAVI. PMID- 27411521 TI - Global epidemiology of atrial fibrillation. PMID- 27411522 TI - [Perioperative ventilation: naturally lung-protective!]. PMID- 27411523 TI - [A new age of mass casuality education? : The InSitu project: realistic training in virtual reality environments]. AB - BACKGROUND: Chief emergency physicians are regarded as an important element in the care of the injured and sick following mass casualty accidents. Their education is very theoretical; practical content in contrast often falls short. Limitations are usually the very high costs of realistic (large-scale) exercises, poor reproducibility of the scenarios, and poor corresponding results. OBJECTIVES: To substantially improve the educational level because of the complexity of mass casualty accidents, modified training concepts are required that teach the not only the theoretical but above all the practical skills considerably more intensively than at present. Modern training concepts should make it possible for the learner to realistically simulate decision processes. This article examines how interactive virtual environments are applicable for the education of emergency personnel and how they could be designed. MATERIALS AND METHODS: Virtual simulation and training environments offer the possibility of simulating complex situations in an adequately realistic manner. The so-called virtual reality (VR) used in this context is an interface technology that enables free interaction in addition to a stereoscopic and spatial representation of virtual large-scale emergencies in a virtual environment. Variables in scenarios such as the weather, the number wounded, and the availability of resources, can be changed at any time. The trainees are able to practice the procedures in many virtual accident scenes and act them out repeatedly, thereby testing the different variants. RESULTS: With the aid of the "InSitu" project, it is possible to train in a virtual reality with realistically reproduced accident situations. These integrated, interactive training environments can depict very complex situations on a scale of 1:1. Because of the highly developed interactivity, the trainees can feel as if they are a direct part of the accident scene and therefore identify much more with the virtual world than is possible with desktop systems. CONCLUSION: Interactive, identifiable, and realistic training environments based on projector systems could in future enable a repetitive exercise with changes within a decision tree, in reproducibility, and within different occupational groups. With a hard- and software environment numerous accident situations can be depicted and practiced. The main expense is the creation of the virtual accident scenes. As the appropriate city models and other three-dimensional geographical data are already available, this expenditure is very low compared with the planning costs of a large-scale exercise. PMID- 27411525 TI - Photoluminescence properties of Eu(3+)/ Sm(3+) activated CaZr4(PO4)6 phosphors. AB - Solid state reaction method was employed for the synthesis of a series of CaZr4(PO4)6: Eu(3+)/Sm(3+) phosphors. The red-emitting CaZr4(PO4)6:Eu(3+) phosphors can be efficiently excited at 396 nm and thereby, exhibit a strong red luminescence predominantly corresponding to the electric dipole transition at 615 nm. Under 405 nm excitation, CaZr4(PO4)6:Sm(3+) phosphors display orange emission with color temperatures approximately around 2200 K. The acquired results reveal that CaZr4(PO4)6: RE(3+) (RE = Eu, Sm) phosphors could be potential candidates for red and orange emitting phosphor, respectively, for UV/blue-pump LEDs. PMID- 27411524 TI - [Above and beyond BMI : Alternative methods of measuring body fat and muscle mass in critically ill patients and their clinical significance]. AB - Obesity leads to better survival in critically ill patients. Although there are several studies confirming this thesis, the "obesity paradox" is still surprising from the clinician's perspective. One explanation for the "obesity paradox" is the fact that the body mass index (BMI), which is used in almost all clinical evaluations to determine weight categories, is not an appropriate measure of fat and skeletal muscle mass and its distribution in critically ill patients. In addition, height and weight are frequently estimated rather than measured. Central obesity has been identified in many disorders as an independent risk factor for an unfavourable outcome. The first clues are to be found in intensive care. Along with obesity, an individual's entire muscle mass is a variable that has an influence on outcome. Central obesity can be measured relatively easily with an abdominal calliper, but the calculation of muscle mass is more complex. A valid and detailed measurement of this can be obtained using computed tomography (CT) images, acquired during routine care. For future clinical observation or interventional studies, single cross-sectional CT is a more sophisticated tool for measuring patients' anthropometry than a measuring tape and callipers. Patients with sarcopenic obesity, for example, who may be at a particular risk, can only be identified using imaging procedures such as single cross-sectional CT. Thus, BMI should take a back seat as an anthropometric tool, both in the clinic and in research. PMID- 27411526 TI - Fertility treatment as a risk factor for maternal request of cesarean delivery in twin pregnancies. AB - OBJECTIVE: A marked increase in the overall cesarean delivery (CD) rate of twin pregnancies has recently been observed. We sought to examine the obstetrical characteristics of patients who chose a non-indicated CD and to investigate the trends in the rate of CD for maternal request over a 5 years period. STUDY DESIGN: A cross sectional retrospective study of twin pregnancies, compared obstetrical characteristics between patients who chose a non-indicated CD and those who delivered vaginally. Deliveries occurred during 2006 and 2011 in a regional tertiary medical center. Patients with any indication for a CD were excluded. A multivariate logistic regression was used to control for confounders. RESULTS: 525 twins were included at the study, 61.7 % (n = 324) were delivered by CD. Of these, 28.7 % (n = 93) were non-indicated. Between the years 2006 and 2011, there was a significant decrease in the rate of non-indicated CD (34.9 vs 23.8 %, OR = 0.58, 95 % CI 0.35-0.94, P = 0.02). Deliveries after fertility treatments or a previous CD had a higher rate of non-indicated CD (51.6 vs. 27.4 %, P < 0.001 and 26.9 vs. 3.5 %, P < 0.001; respectively). In the multivariate analysis, maternal age (OR = 1.08, 95 % CI 1.01-1.15), previous CD (OR = 15.75, 95 % CI 5.82-42.67) and fertility treatments (OR = 2.16, 95 % CI 1.14-4.10) were found to be independent risk factors for a non-indicated CD. Furthermore, parity was found to be an independent protective factor (OR = 0.75, 95 % CI 0.61-0.92). CONCLUSION: In our study population, there was a significant decrease in the rate of non-indicated CD over a five-year period. Maternal age, fertility treatments and previous CD were found to be independent risk factors for non-indicated CD in twin pregnancies. PMID- 27411527 TI - Role of minimally invasive surgery for adult spinal deformity in preventing complications. AB - With the aging population, there is a rising prevalence of degenerative spinal deformity and need of surgical care for these patients. Surgical treatment for adult spinal deformity (ASD) is often fraught with a high rate of complications. Minimally invasive surgery (MIS) has for the past decade been adopted by spine surgeons to treat ASD in the hopes of reducing access-related morbidity and perioperative complications. The benefits of MIS approach in general and recent development of MIS techniques to avoid long-term complications such as pseudoarthrosis or proximal junctional kyphosis are reviewed. PMID- 27411528 TI - Complications of surgical intervention in adult lumbar scoliosis. AB - If nonoperative measures are unsuccessful in managing the pain and disability of adult spinal deformities, surgical correction may provide the potential for significant improvement in a patient's quality of life. However, these procedures have a relatively high risk of complications. Identifying patients that may benefit from surgical intervention requires a thorough understanding of potential complications and managing the risks of any individual patient. Complications do not necessarily result in poor outcomes, and good outcomes are not always complication free. Higher risk patients potentially have more to gain, even if they experience complications. With the rapidly expanding senior population and expanded capabilities to manage high-risk patients, it is helpful to consider the lessons provided by ever expanding databases of outcome measures to refine the surgical decision-making process. PMID- 27411530 TI - Teaching Engineering Ethics to PhD Students: A Berkeley-Delft Initiative : Commentary on "Ethics Across the Curriculum: Prospects for Broader (and Deeper) Teaching and Learning in Research and Engineering Ethics". AB - A joint effort by the University of California at Berkeley and Delft University of Technology to develop a graduate engineering ethics course for PhD students encountered two types of challenges: academic and institutional. Academically, long-term collaborative research efforts between engineering and philosophy faculty members might be needed before successful engineering ethics courses can be initiated; the teaching of ethics to engineering graduate students and collaborative research need to go hand-in-hand. Institutionally, both bottom-up approaches at the level of the faculty and as a joint research and teaching effort, and top-down approaches that include recognition by a University's administration and the top level of education management, are needed for successful and sustainable efforts to teach engineering ethics. PMID- 27411529 TI - RNAi-mediated knockdown of the voltage gated sodium ion channel TcNav causes mortality in Tribolium castaneum. AB - The voltage-gated sodium ion channel (VGSC) belongs to the largest superfamily of ion channels. Since VGSCs play key roles in physiological processes they are major targets for effective insecticides. RNA interference (RNAi) is widely used to analyse gene function, but recently, it has shown potential to contribute to novel strategies for selectively controlling agricultural insect pests. The current study evaluates the delivery of dsRNA targeted to the sodium ion channel paralytic A (TcNav) gene in Tribolium castaneum as a viable means of controlling this insect pest. Delivery of TcNav dsRNA caused severe developmental arrest with larval mortalities up to 73% post injection of dsRNA. Injected larvae showed significant (p < 0.05) knockdown in gene expression between 30-60%. Expression was also significantly (p < 0.05) reduced in pupae following injection causing 30% and 42% knockdown for early and late pupal stages, respectively. Oral delivery of dsRNA caused dose-dependant mortalities of between 19 and 51.34%; this was accompanied by significant (p < 0.05) knockdown in gene expression following 3 days of continuous feeding. The majority of larvae injected with, or fed, dsRNA died during the final larval stage prior to pupation. This work provides evidence of a viable RNAi-based strategy for insect control. PMID- 27411531 TI - A pain in the back: anaerobic vertebral spondylitis of hematogenous origin. PMID- 27411533 TI - A novel surgical technique for bleeding duodenal varices after failure of balloon occluded retrograde transvenous obliteration: a case report. AB - BACKGROUND: Duodenal varices are a low-frequency cause of gastrointestinal bleeding; however, greater than 40 % mortality has been reported after the initial bleeding episode. CASE PRESENTATION: This report describes a 72-year-old woman with bleeding duodenal varices treated by surgery after failure of balloon occluded retrograde transvenous obliteration (B-RTO). The patient presented with profuse melena. Emergent upper endoscopy was immediately performed, and bleeding duodenal varices in the second portion of the duodenum were seen. Endoscopic band ligation was attempted first followed by B-RTO; however, the combined procedures failed. Laparotomy under general anesthesia was then performed, and the venous collaterals were cannulated using an 18-gauge needle. Following intraoperative angiography, the venous collateral was ligated on the peripheral side of the needle entry point, and ethanolamine oleate was injected into the afferent collateral vessel. Endoscopic examination on postoperative day 4 showed embolization of the duodenal varices. The patient was discharged on postoperative day 11. CONCLUSIONS: This technique is simple and effective, and we believe it is a potential alternative surgical treatment for duodenal varices with portal hypertension. PMID- 27411532 TI - Time trends in Staphylococcus aureus bacteremia, 1988-2010, in a tertiary center with high methicillin resistance rates. AB - INTRODUCTION: Changes in the epidemiology of Staphylococcus aureus bacteremia (SAB) have been described in recent decades. Decreased mortality has been reported over time, mostly from countries with low methicillin resistance rates. We aimed to describe time trends in SAB in a tertiary center with high methicillin resistance rates. METHODS: We retrospectively analyzed 1692 patients with SAB, and compared between three time periods: 1988-1994 (342 patients), 1998 2004 (597 patients) and 2005-2010 (753 patients). RESULTS: In our cohort, 30 days mortality increased significantly with time, reaching 42.9 % during 2005-2010. The latter period was characterized by higher rates of older patients (35.1 % aged 80 years and older), with lower functional capacity (46.5 % bedridden) and higher rates of comorbidities (33.6 % renal disease, 24.8 % heart failure, 19.0 % dementia). These patients were more likely to be ventilated (18.7 %) and carry a urinary catheter at presentation (46.6 %); present with septic shock (15.9 %) and have pneumonia (20.5 %) or endocarditis (7.2 %) as source. Similar characteristics were found among patients younger than 50 years and with independent functional status. No significant increase in methicillin resistant Staph aureus (MRSA) rates or inappropriate empirical therapy was demonstrated during 2005-2010. CONCLUSIONS: In our cohort, increased mortality in recent years in patients with SAB can be explained by baseline condition of patients. MRSA or inappropriate empiric therapy did not explain the increase in mortality. The patients afflicted with SAB changed over time. Epidemiology and outcomes of SAB vary with time and according to geographical location. External validity of studies should be taken into consideration. PMID- 27411534 TI - A gastrointestinal stromal tumor found in perforated Meckel's diverticulum. AB - BACKGROUND: Meckel's diverticulum is the most common anomaly of the gastrointestinal tract. It is usually asymptomatic, but approximately 4 % present with complications such as bleeding, intestinal obstruction, and inflammation, while perforation is rare. Carcinoid or gastrointestinal stromal tumors are occasionally found in the resected specimens of Meckel's diverticulum, particularly in the context of perforation. CASE PRESENTATION: A 62-year-old male with a recent history of admission and evaluation for hematochezia presented with abdominal pain. His physical examination was consistent with peritonitis. Results of laboratory testing were significant for white blood cell count of 32,000/MUL. CT scan of the abdomen revealed pneumoperitoneum. During the exploratory laparotomy, perforated Meckel's diverticulum was encountered and segmental bowel resection was performed. Histological examination findings were compatible with gastrointestinal stromal tumor within Meckel's diverticulum. CONCLUSIONS: While gastrointestinal stromal tumor is a rare finding in Meckel's diverticula, the potential for the coexistence of this and other tumors suggests that segmental resection of the small bowel should be considered in the treatment of perforated Meckel's diverticulum. PMID- 27411536 TI - Bacterial communities associated with sulfonamide antibiotics degradation in sludge-amended soil. AB - This study investigated the degradation of sulfonamide antibiotics (SAs) and microbial community changes in sludge-amended soil. In batch experiments, SA degradation was enhanced by addition of spent mushroom compost (SMC), SMC extract, and extract-containing microcapsule, with SMC showing higher SA degradation rate than the other additives in soil-sludge mixtures. In bioreactor experiments, the degradation of SAs in soil-sludge mixtures was in the order of sulfamethoxazole > sulfadimethoxine > sulfamethazine during four times of SA addition. SA removal was higher in soil-sludge mixtures than in soil alone. The bacterial composition differed in soil-sludge mixtures with and without SMC. In total, 44 differentially distributed bacterial genera were identified from different experimental settings and stages. Four bacterial genera, Acinetobacter, Alcaligenes, Brevundimonas, and Pseudomonas, were previously found involved in SA degradation, and 20 of the 44 bacterial genera were previously found in aromatic hydrocarbon degradation. Therefore, these bacteria have high potential to be SA degradation bacteria in this study. PMID- 27411535 TI - Effect of cadmium accumulation on mineral nutrient levels in vegetable crops: potential implications for human health. AB - Consumption of vegetables is often the predominant route whereby humans are exposed to the toxic metal Cd. Health impacts arising from Cd consumption may be influenced by changes in the mineral nutrient content of vegetables, which may occur when plants are exposed to Cd. Here, we subjected model root (carrot) and leaf (lettuce) vegetables to soil Cd concentrations of 0.3, 1.5, 3.3, and 9.6 MUg g(-1) for 10 weeks to investigate the effect of Cd exposure on Cd accumulation, growth performance, and mineral nutrient homeostasis. The findings demonstrated that Cd accumulation in lettuce (20.1-71.5 MUg g(-1)) was higher than that in carrot (3.2-27.5 MUg g(-1)), and accumulation exceeded the maximum permissible Cd concentration in vegetables when soil contained more than 3.3 MUg g(-1) of Cd. There was a marked hormetic effect on carrot growth at a soil Cd concentration of 3.3 MUg g(-1), but increasing the Cd concentration to 9.6 MUg g(-1) caused decreased growth in both crops. Additionally, in most cases, there was a positive correlation between Cd and the mineral nutrient content of vegetables, which was due to physiological changes in the plants causing increased uptake and/or translocation. This may suggest a general mechanism whereby the plant compensated for disrupted mineral nutrient metabolism by increasing nutrient supply to its tissues. Increased nutrient levels could potentially offset some risks posed to humans by increased Cd levels in crops, and we therefore suggest that changes in mineral nutrient levels should be included more widely in the risk assessment of potentially toxic metal contamination. Graphical abstract The Cd concentration (MUg g-1 in dry matter) in the root, shoot and translocation factor (TF) of Cd from root to shoot in the carrot and lettuce, and the percentage of root Cd to the gross Cd contents (%) in carrot (C) and lettuce (D) exposed to soil Cd (0 (control), 1, 3, and 9 MUg g-1) for 70 days. Values are means +/- SD (n = 5). PMID- 27411537 TI - Influence of the natural Rio Negro water on the toxicological effects of a crude oil and its chemical dispersion to the Amazonian fish Colossoma macropomum. AB - The increment in crude oil exploitation over the last decades has considerably increased the risk of polycyclic aromatic hydrocarbon (PAH) contamination to Amazonian aquatic environments, especially for the black water environments such as the Rio Negro. The present work was designed to evaluate the acute toxicity of the Urucu crude oil (CO), the chemically dispersed Urucu crude oil (CO + D), and the dispersant alone (D) to the Amazonian fish Colossoma macropomum. Acute toxicity tests were performed, using a more realistic approach, where fish were acclimated to both groundwater (GW), used as internal control, and natural Rio Negro water (RNW) and exposed to CO, CO + D and D. Then, biomarkers such as ethoxyresorufin-O-deethylase (EROD), superoxide dismutase (SOD), lipid peroxidation (LPO), serum sorbitol dehydrogenase (s-SDH) in liver, DNA damage in blood cells, and the presence of the benzo[a]pyrene-type, pyrene-type, and naphthalene-type metabolites in fish bile were assessed. Fish exposed to CO and CO + D, at both water types tested, presented increased biomarker responses and higher PAH-type metabolites in the bile. However, fish exposed to these treatments after the acclimation to RNW increased the levels of LPO, s-SDH (hepatotoxicity), DNA damage in blood cells (genotoxicity), and benzo[a]pyrene type metabolites when compared to fish in GW. Our data suggests that some physicochemical properties of Rio Negro water (i.e., presence of natural organic matter (NOM)) might cause mild chemical stress responses in fish, which can make it more susceptible to oxidative stress following exposure to crude oil, particularly to those chemically dispersed. PMID- 27411538 TI - Effects of agricultural fungicides on microorganisms associated with floral nectar: susceptibility assays and field experiments. AB - Pesticides have become an inseparable element of agricultural intensification. While the direct impact of pesticides on non-target organisms, such as pollinators, has recently received much attention, less consideration has been given to the microorganisms that are associated with them. Specialist yeasts and bacteria are known to commonly inhabit floral nectar and change its chemical characteristics in numerous ways, possibly influencing pollinator attraction. In this study, we investigated the in vitro susceptibility of nectar yeasts Metschnikowia gruessi, Metschnikowia reukaufii, and Candida bombi to six widely used agricultural fungicides (prothioconazole, tebuconazole, azoxystrobin, fenamidone, boscalid, and fluopyram). Next, a commercial antifungal mixture containing tebuconazole and trifloxystrobin was applied to natural populations of the plant Linaria vulgaris and the occurrence, abundance, and diversity of nectar inhabiting yeasts and bacteria was compared between treated and untreated plants. The results showed that prothioconazole and tebuconazole were highly toxic to nectar yeasts, inhibiting their growth at concentrations varying between 0.06 and 0.5 mg/L. Azoxystrobin, fenamidone, boscalid, and fluopyram on the other hand exhibited considerably lower toxicity, inhibiting yeast growth at concentrations between 1 and 32 mg/L or in many cases not inhibiting microbial growth at all. The application of the antifungal mixture in natural plant populations resulted in a significant decrease in the occurrence and abundance of yeasts in individual flowers, but this did not translate into noticeable changes in bacterial incidence and abundance. Yeast and bacterial species richness and distribution did not also differ between treated and untreated plants. We conclude that the application of fungicides may have negative effects on the abundance of nectar yeasts in floral nectar. The consequences of these effects on plant pollination processes in agricultural systems warrant further investigation. PMID- 27411540 TI - Bovine Serum Albulmin Protein-Templated Silver Nanocluster (BSA-Ag13 ): An Effective Singlet Oxygen Generator for Photodynamic Cancer Therapy. AB - This paper reports a novel synthesis approach of bovine serum albumin (BSA) protein-templated ultrasmall (<2 nm) Ag nanocluster (NC) with strong singlet oxygen generation capacity for photodynamic therapy (PDT). An atomically precise BSA-Ag13 NC (i.e., 13 Ag atoms per cluster) is successfully synthesized for the first time by using NaOH-dissolved NaBH4 solution as the controlling reducing agent. The ubiquitous size of BSA-Ag13 NC results in unique behaviors of its photoexcited states as characterized by the ultrafast laser spectroscopy using time-correlated single photon counting and transient absorption techniques. In particular, triply excited states can be largely present in the excited BSA-Ag13 NC and readily sensitized molecular oxygen to produce singlet oxygen (1 O2 ) with a high quantum efficiency (~1.26 using Rose Bengal as a standard). This value is much higher than its Au analogue (i.e., ~0.07 for BSA-Au25 NC) and the commonly available photosensitizers. Due to the good cellular uptake and inherent biocompatibility imparted by the surface protein, BSA-Ag13 NC can be applied as an effective PDT agent in generating 1 O2 to kill cancer cell as demonstrated in this study. PMID- 27411539 TI - Comparison of antioxidant enzyme activities and DNA damage in chickpea (Cicer arietinum L.) genotypes exposed to vanadium. AB - The present study was done to elucidate the effects of vanadium (V) on photosynthetic pigments, membrane damage, antioxidant enzymes, protein, and deoxyribonucleic acid (DNA) integrity in the following chickpea genotypes: C-44 (tolerant) and Balkasar (sensitive). Changes in these parameters were strikingly dependent on levels of V, at 60 and 120 mg V L(-1) induced DNA damage in Balkasar only, while photosynthetic pigments and protein were decreased from 15 to 120 mg V L(-1) and membrane was also damaged. It was shown that photosynthetic pigments and protein production declined from 15 to 120 mg V L(-1) and the membrane was also damaged, while DNA damage was not observed at any level of V stress in C-44. Moreover, the antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were increased in both genotypes of chickpea against V stress; however, more activities were observed in C-44 than Balkasar. The results suggest that DNA damage in sensitive genotypes can be triggered due to exposure of higher vanadium. PMID- 27411541 TI - Epstein-Barr virus gastric ulcer associated with ruxolitinib. PMID- 27411542 TI - The pathophysiological basis and consequences of fever. AB - There are numerous causes of a raised core temperature. A fever occurring in sepsis may be associated with a survival benefit. However, this is not the case for non-infective triggers. Where heat generation exceeds heat loss and the core temperature rises above that set by the hypothalamus, a combination of cellular, local, organ-specific, and systemic effects occurs and puts the individual at risk of both short-term and long-term dysfunction which, if severe or sustained, may lead to death. This narrative review is part of a series that will outline the pathophysiology of pyrogenic and non-pyrogenic fever, concentrating primarily on the pathophysiology of non-septic causes. PMID- 27411544 TI - Erratum to: Immunoanalysis for environmental monitoring and human health. PMID- 27411543 TI - Hyperadherence of Pseudomonas taiwanensis VLB120DeltaC increases productivity of (S)-styrene oxide formation. AB - The attachment strength of biofilm microbes is responsible for the adherence of the cells to surfaces and thus is a critical parameter in biofilm processes. In tubular microreactors, aqueous-air segmented flow ensures an optimal oxygen supply and prevents excessive biofilm growth. However, organisms growing in these systems depend on an adaptation phase of several days, before mature and strong biofilms can develop. This is due to strong interfacial forces. In this study, a hyperadherent mutant of Pseudomonas taiwanensis VLB120DeltaCeGFP possessing an engineered cyclic diguanylate metabolism, was applied to a continuous biofilm process for the production of (S)-styrene oxide. Cells of the mutant P. taiwanensis VLB120DeltaCeGFP Delta04710, showing the same specific activity as the wild type, adhered substantially stronger to the substratum. Adaptation to the high interfacial forces was not necessary in these cases. Thereby, 40% higher final product concentrations were achieved and the maximal volumetric productivity of the parent strain was significantly surpassed by P. taiwanensis VLB120DeltaCeGFP Delta04710. Applying mutants with strong adhesion in biofilm based catalysis opens the door to biological process control in future applications of catalytic biofilms using other industrially relevant strains. PMID- 27411545 TI - Metaproteomic analysis of atmospheric aerosol samples. AB - Metaproteomic analysis of air particulate matter provides information about the abundance and properties of bioaerosols in the atmosphere and their influence on climate and public health. We developed and applied efficient methods for the extraction and analysis of proteins from glass fiber filter samples of total, coarse, and fine particulate matter. Size exclusion chromatography was applied to remove matrix components, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was applied for protein fractionation according to molecular size, followed by in-gel digestion and LC-MS/MS analysis of peptides using a hybrid Quadrupole-Orbitrap MS. Maxquant software and the Swiss-Prot database were used for protein identification. In samples collected at a suburban location in central Europe, we found proteins that originated mainly from plants, fungi, and bacteria, which constitute a major fraction of primary biological aerosol particles (PBAP) in the atmosphere. Allergenic proteins were found in coarse and fine particle samples, and indications for atmospheric degradation of proteins were observed. Graphical abstract Workflow for the metaproteomic analysis of atmospheric aerosol samples. PMID- 27411546 TI - Development of a biotinylated broad-specificity single-chain variable fragment antibody and a sensitive immunoassay for detection of organophosphorus pesticides. AB - Organophosphorus pesticides (OPs) are the most widely used pesticides in agriculture, and OP residues have been broadly reported in food and environmental samples. The aim of this study is to develop a recombinant antibody-based broad specificity immunoassay for OPs. A phage display library was prepared from a mouse pre-immunized with a generic immunogen of OPs, and a single-chain variable fragment (scFv) antibody was selected. The selected scFv antibody was fused with biotin acceptor domain (BAD) and overexpressed as an inclusion body in Escherichia coli BL21 (DE3). Then, the protein was refolded by stepwise urea gradient dialysis and biotinylated in vitro by E. coli biotin ligase (BirA). Subsequently, the scFv-BAD protein was purified from the biotinylated system with high yield (66.7 mg L(-1)) and confirmed by SDS-PAGE and Western blot. Based on the biotinylated scFv-BAD, a sensitive and broad-specificity competitive indirect enzyme-linked immunosorbent assay (ciELISA) for detection of OPs was developed. The cross-reactivity (CR) studies demonstrated that the ciELISA described here exhibited the broadest detection spectrum for OPs up to now, and 30 OPs could be determined with 50 % inhibition value (IC50) values ranging from 19.4 to 515.2 ng mL(-1). Moreover, the developed ciELISA was used for the recovery study of the spiked samples and showed satisfactory recoveries. Graphical Abstract Schematic diagram of the development of biotinylated broad-specificity single-chain variable fragment antibody-based immunoassay for organophosphorus pesticides. PMID- 27411547 TI - Efficient production of (2)H, (13)C, (15)N-enriched industrial enzyme Rhizopus chinensis lipase with native disulfide bonds. AB - BACKGROUND: In order to use most modern methods of NMR spectroscopy to study protein structure and dynamics, isotope-enriched protein samples are essential. Especially for larger proteins (>20 kDa), perdeuterated and Ile (delta1), Leu, and Val methyl-protonated protein samples are required for suppressing nuclear relaxation to provide improved spectral quality, allowing key backbone and side chain resonance assignments needed for protein structure and dynamics studies. Escherichia coli and Pichia pastoris are two of the most popular expression systems for producing isotope-enriched, recombinant protein samples for NMR investigations. The P. pastoris system can be used to produce (13)C, (15)N enriched and even (2)H,(13)C, (15)N-enriched protein samples, but efficient methods for producing perdeuterated proteins with Ile (delta1), Leu and Val methyl-protonated groups in P. pastoris are still unavailable. Glycosylation heterogeneity also provides challenges to NMR studies. E. coli expression systems are efficient for overexpressing perdeuterated and Ile (delta1), Leu, Val methyl protonated protein samples, but are generally not successful for producing secreted eukaryotic proteins with native disulfide bonds. RESULTS: The 33 kDa protein-Rhizopus chinensis lipase (RCL), an important industrial enzyme, was produced using both P. pastoris and E. coli BL21 trxB (DE3) systems. Samples produced from both systems exhibit identical native disulfide bond formation and similar 2D NMR spectra, indicating similar native protein folding. The yield of (13)C, (15)N-enriched r27RCL produced using P. pastoris was 1.7 times higher that obtained using E. coli, while the isotope-labeling efficiency was ~15 % lower. Protein samples produced in P. pastoris exhibit O-glycosylation, while the protein samples produced in E. coli were not glycosylated. The specific activity of r27RCL from P. pastoris was ~1.4 times higher than that produced in E. coli. CONCLUSIONS: These data demonstrate efficient production of (2)H, (13)C, (15)N enriched, Ile (delta1), Leu, Val methyl-protonated eukaryotic protein r27RCL with native disulfides using the E. coli BL21 trxB (DE3) system. For certain NMR studies, particularly efforts for resonance assignments, structural studies, and dynamic studies, E. coli provides a cost-effective system for producing isotope enriched RCL. It should also be potential for producing other (2)H, (13)C, (15)N enriched, Ile (delta1), Leu, Val methyl-protonated eukaryotic proteins with native disulfide bonds. PMID- 27411548 TI - Identification of a novel human papillomavirus by metagenomic analysis of vaginal swab samples from pregnant women. AB - BACKGROUND: The number of members in the genus Gammapapillomavirus of Family Papillomaviridae has recently been expanding most rapidly. The aim of this study was to characterize a novel human gammapapillomavirus type identified in a vaginal swab from a 25-year-old pregnant woman suffering from vaginitis. METHODS: Viral metagenomics method was used to detect the viral sequences in 88 vaginal swab samples collected from 88 pregnant women with vaginitis. A novel papillomavirus, named HPV-ZJ01 (GenBank no. KX082661), was detected in one sample and its complete genome sequence was amplified by PCR and sequenced by Sanger walking. Phylogenetic analyses based on the complete genome and the L1 protein of HPV-ZJ01 and other representative human papillomaviruses were done, respectively. Further PCR screening was performed in vaginal swabs (n = 135), cervical smears (n = 40) and cervical cancer tissues (n = 40) using nested-PCR primers designed based on HPV-ZJ01 sequence to investigate the prevalence of HPV-ZJ01. RESULTS: The genome of HPV-ZJ01 is 7,358 bp in length with a GC content of 37.8 %. HPV ZJ01 was predicted to contain six open reading frames (E6, E7, E1, E2, L2, and L1) and a non-coding long control region (LCR). The genome shared the highest overall similarity to HPV-166, with 70.6 % nucleotide sequence identity while its L1 gene shared the highest nucleotide similarity to HPV-162, with 71.1 % sequence identity. Phylogenetic analysis suggested that HPV-ZJ01 belongs to a novel HPV type in the Gamma-PV genus, species Gamma-19, already containing HPV161, HPV162 and HPV166. PCR screening results indicated that none of the other samples were positive for HPV-ZJ01 except the original HPV-ZJ01 positive vaginal swab specimen. CONCLUSION: The genome sequence of a novel type of species Gamma-19 HPV was characterized. The screening PCR results suggested that HPV-ZJ01 is not associated with any of the cervical cancer samples tested. In order to confirm the prevalence and disease association, if any, for HPV-ZJ01, a further study with different sample types and a larger sample size is needed. PMID- 27411549 TI - Early Adoption of the SSO-ASTRO Consensus Guidelines on Margins for Breast Conserving Surgery with Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: Initial Experience from Memorial Sloan Kettering Cancer Center. AB - BACKGROUND: Reexcision rates in patients undergoing breast-conserving surgery (BCS) for early-stage invasive breast cancer are highly variable. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines to help standardize practice. We sought to determine reexcision rates before and after guideline adoption at our institution. METHODS: We identified patients with stage I or II invasive breast cancer initially treated with BCS between June 1, 2013, and October 31, 2014. Margins were defined as positive (tumor on ink), close (<=1 mm), or negative (>1 mm), and were recorded for both invasive cancer and ductal carcinoma-in situ (DCIS) components. Reexcision rates were quantified, characteristics were compared between groups, and multivariable logistic regression was performed. RESULTS: A total of 1205 patients were identified, 504 before and 701 after the guideline adoption (January 1, 2014). Clinical and pathologic characteristics were similar between time periods. Reexcision rates significantly declined from 21.4 to 15.1 % (p = 0.006) after guideline adoption. A multivariable model identified extensive intraductal component (odds ratio [OR] 2.5, 95 % confidence interval [CI] 1.2-5.2), multifocality (OR 2.0, 95 % CI 1.2-3.6), positive (OR 844.4, 95 % CI 226.3-5562.5) and close (OR 38.3, 95 % CI 21.5-71.8) ductal carcinoma-in situ margin, positive (OR 174.2, 95 % CI 66.2-530.0) and close (OR 6.4, 95 % CI 3.0-13.6) invasive margin, and time period (OR 0.5, 95 % CI 0.3-0.9 for post vs. pre) as independently associated with reexcision. CONCLUSIONS: Overall reexcision rates declined significantly after guideline adoption. Close invasive margins were associated with higher rates of reexcision than negative invasive margins in both time periods; however, the effect diminished in the postguideline adoption period. Thus, we expect continued decline in reexcision rates as adherence to guidelines becomes more uniform. PMID- 27411550 TI - The Impact of the Affordable Care Act on North Carolinian Breast Cancer Patients Seeking Financial Support for Treatment. AB - BACKGROUND: The Affordable Care Act (ACA) was instated on 23 March 2010 to improve healthcare quality, reduce costs, and increase access. The Pretty in Pink Foundation (PIPF), a non-profit 501(C)(3) organization in North Carolina, provides financial assistance and in-kind support to individuals seeking help with breast cancer care. The objective of this study was to determine whether sociodemographic variables and treatment services varied among PIPF recipients since enactment of the ACA. METHODS: North Carolinians who received financial assistance from the PIPF between 1 January 2013 and 31 December 2014 were included in the study, and the cohort was divided into two groups based on receipt of assistance before or after the enactment of the ACA. Descriptive statistics were tabulated as frequencies. Comparative univariate analysis between both groups was conducted using the chi (2) and Mann-Whitney U tests. All tests were two-sided and a p value <0.05 was considered statistically significant. All analyses were conducted using Stata. RESULTS: Overall, 1016 individuals fulfilled the inclusion criteria, and the median age of the cohort was 49 years (interquartile range 45-55). The ACA groups did not differ significantly by age, race, and sex; however, the groups varied with respect to income, employment, and clinical stage. In addition, the groups differed on the types of services for which they received financial assistance, but no difference was observed between groups with respect to insurance status. CONCLUSION: Since the enactment of the health insurance market component of the ACA, there has been a reduction in subjects receiving assistance from the PIPF; however, no change in their insurance status has been observed. PMID- 27411551 TI - Immature Colon Carcinoma Transcript-1 (ICT1) Expression Correlates with Unfavorable Prognosis and Survival in Patients with Colorectal Cancer. AB - BACKGROUND: Colorectal cancer (CRC) is the third leading cause of death from cancer worldwide. Immature colon carcinoma transcript-1 (ICT1) has been reported to be correlated with lung cancer; however, whether ICT1 is a functional gene in CRC, as well as the molecular mechanism underlying ICT1 mediation of colorectal tumor formation, remains unknown. METHODS: The expression of ICT1 was firstly determined by using immunohistochemistry in 861 CRC specimens. The correlation of ICT1 expression with clinicopathological parameters and the survival rate was analyzed. Furthermore, we investigated the effect of ICT1 silencing on CRC cell proliferation and migration by MTT, colony formation, flow cytometry, and transwell in vitro. RESULTS: ICT1 is highly expressed in a cohort of human CRCs, and that higher ICT1 expression may lead to reduced overall survival rate of CRC. Likewise, ICT1 silencing lowered the cell viability through cell-cycle arrest, inhibited cell migration, and induced apoptosis in CRC. We further revealed a novel mechanism in which ICT1 promoted CRC growth via the intracellular AMPK, SAPK/JNK, and PARP signaling pathways. CONCLUSIONS: Our data showed that ICT1 could be an important target for CRC diagnosis and treatment. PMID- 27411552 TI - Comparison of 1800 Robotic and Open Partial Nephrectomies for Renal Tumors. AB - BACKGROUND: Only a few studies have compared the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN). This study aimed to compare perioperative and oncologic outcomes of RPN and OPN. METHODS: The data of all patients who underwent partial nephrectomy from 2006 to 2014 in six academic departments of urology were retrospectively collected. Perioperative outcomes were compared between OPN and RPN patients. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The study included 1800 patients: 937 who underwent RPN and 863 who underwent OPN. The patients in the robotic group had smaller tumors (33.1 vs. 39.9 mm; p < 0.001) but comparable RENAL scores (6.8 vs. 6.7; p = 0.37). The complication rate was higher in the OPN group (28.6 vs. 18 %; p < 0.001). The OPN patients had greater estimated blood loss (359.5 vs. 275 ml; p < 0.001) and more frequent hemorrhagic complications (12.1 vs. 6.9 %; p < 0.001). The robotic approach was associated with a shorter warm ischemia time (WIT 15.7 vs. 18.6 min; p < 0.001) and a shorter hospital of stay (4.7 vs. 10.1 days; p < 0.001). In the propensity score-weighted analysis, the inverse probability of treatment weighting adjusted odds ratio for the risk of complication after OPN versus RPN was 2.11 (95 % confidence interval, 1.53-2.91; p < 0.001). After a median postoperative follow-up period of 13 months for OPN and 39 months for RPN (p < 0.001), CSS and RFS were similar in the two groups. In the multivariate analysis, RPN showed an impact on the occurrence of a complication but had no effect on WIT or RFS. CONCLUSION: In this study, RPN was less morbid than OPN, with lower complications, less blood loss, and a shorter hospital of stay. The intermediate-term oncologic outcomes were similar in the two groups. PMID- 27411553 TI - Homology modeling, substrate docking, and molecular simulation studies of mycobacteriophage Che12 lysin A. AB - Mycobacteriophages produce lysins that break down the host cell wall at the end of lytic cycle to release their progenies. The ability to lyse mycobacterial cells makes the lysins significant. Mycobacteriophage Che12 is the first reported temperate phage capable of infecting and lysogenising Mycobacterium tuberculosis. Gp11 of Che12 was found to have Chitinase domain that serves as endolysin (lysin A) for Che12. Structure of gp11 was modeled and evaluated using Ramachandran plot in which 98 % of the residues are in the favored and allowed regions. Che12 lysin A was predicted to act on NAG-NAM-NAG molecules in the peptidoglycan of cell wall. The tautomers of NAG-NAM-NAG molecule were generated and docked with lysin A. The stability and binding affinity of lysin A - NAG-NAM-NAG tautomers were studied using molecular dynamics simulations. PMID- 27411554 TI - Diagnosis of Acute Appendicitis by Endoscopic Retrograde Appendicitis Therapy (ERAT): Combination of Colonoscopy and Endoscopic Retrograde Appendicography. AB - BACKGROUND: Acute appendicitis is the most common abdominal emergency, but the diagnosis of appendicitis remains a challenge. Endoscopic retrograde appendicitis therapy (ERAT) is a new and minimally invasive procedure for the diagnosis and treatment of acute appendicitis. AIM: To investigate the diagnostic value of ERAT for acute appendicitis by the combination of colonoscopy and endoscopic retrograde appendicography (ERA). METHODS: Twenty-one patients with the diagnosis of suspected uncomplicated acute appendicitis who underwent ERAT between November 2014 and January 2015 were included in this study. The main outcomes, imaging findings of acute appendicitis including colonoscopic direct-vision imaging and fluoroscopic ERA imaging, were retrospectively reviewed. Secondary outcomes included mean operative time, mean hospital stay, rate of complication, rate of appendectomy during follow-up period, and other clinical data. RESULTS: The diagnosis of acute appendicitis was established in 20 patients by positive ERA (5 patients) or colonoscopy (1 patient) alone or both (14 patients). The main colonoscopic imaging findings included mucosal inflammation (15/20, 75 %), appendicoliths (14/20, 70 %), and maturation (5/20, 25 %). The key points of ERA for diagnosing acute appendicitis included radiographic changes of appendix (17/20, 85 %), intraluminal appendicoliths (14/20, 70 %), and perforation (1/20, 5 %). Mean operative time of ERAT was 49.7 min, and mean hospital stay was 3.3 days. No patient converted to emergency appendectomy. Perforation occurred in one patient after appendicoliths removal was not severe and did not require invasive procedures. During at least 1-year follow-up period, only one patient underwent laparoscopic appendectomy. CONCLUSION: ERAT is a valuable procedure of choice providing a precise yield of diagnostic information for patients with suspected acute appendicitis by combination of colonoscopy and ERA. PMID- 27411556 TI - Discovery of HIV Type 1 Aspartic Protease Hit Compounds through Combined Computational Approaches. AB - A combination of computational techniques and inhibition assay experiments was employed to identify hit compounds from commercial libraries with enhanced inhibitory potency against HIV type 1 aspartic protease (HIV PR). Extensive virtual screening with the aid of reliable pharmacophore models yielded five candidate protease inhibitors. Subsequent molecular dynamics and molecular mechanics Poisson-Boltzmann surface area free-energy calculations for the five ligand-HIV PR complexes suggested a high stability of the systems through hydrogen-bond interactions between the ligands and the protease's flaps (Ile50/50'), as well as interactions with residues of the active site (Asp25/25'/29/29'/30/30'). Binding-energy calculations for the three most promising compounds yielded values between -5 and -10 kcal mol(-1) and suggested that van der Waals interactions contribute most favorably to the total energy. The predicted binding-energy values were verified by in vitro inhibition assays, which showed promising results in the high nanomolar range. These results provide structural considerations that may guide further hit-to-lead optimization toward improved anti-HIV drugs. PMID- 27411557 TI - Role of Acupuncture in the Treatment or Prevention of Migraine, Tension-Type Headache, or Chronic Headache Disorders. AB - OBJECTIVE: To summarize the current evidence that evaluates the effectiveness of acupuncture for the treatment or prevention of migraine, tension-type headache, and chronic headache disorders. METHODS: Findings from selected systematic reviews and meta-analyses are summarized. RESULTS: Recently published systematic reviews and meta-analyses demonstrate that acupuncture is associated with improved clinical outcomes compared to routine care only, medical management, and sham acupuncture 2 months after randomization. The evidence in support of acupuncture's comparative effectiveness at longer follow-up periods is mixed. Cost effectiveness analyses conducted in the United Kingdom and Germany suggest that acupuncture is a cost-effective treatment option in those countries. There are few or no cost-effectiveness studies of acupuncture in the United States. DISCUSSION: This brief review of the current, published evidence does not include a discussion of potential risks or adverse events associated with acupuncture. There is also the question of the extent to which placebo effects might contribute to acupuncture's clinical effectiveness. From a purely comparative effectiveness perspective, however, the evidence from clinical trials and meta analyses makes a compelling case in support of a potentially important role for acupuncture as part of a treatment plan for patients with migraine, tension-type headache, and several different types of chronic headache disorders. PMID- 27411558 TI - Current Status and Future Directions of Nanoparticulate Strategy for Cancer Immunotherapy. AB - BACKGROUND: Rapid advancement over the past few decades in cancer immunotherapy provides life-saving options for cancer patients. However, commonly used strategies including small molecules and various biomacromolecule-based therapeutics suffer from serious off-target toxicity and a lack of stability in the circulation. OBJECTIVE: To overcome these problems, various nanoparticulate delivery systems have been developed to achieve controlled and sustained drug release, improved stability and pharmacokinetic profiles, and tumor specificity to reduce off-target adverse effects. METHOD: We reviewed representative studies on multiple nanoparticulate platform systems for delivering therapeutics in cancer immunotherapy, and discussed the advances and perspectives for the future development of novel therapeutics in cancer immunotherapy. Results and Perspectives: Nanoparticles for the controlled delivery of immune modulating agents represents a viable approach in cancer immunotherapy. Besides seeking novel carrier systems or new materials, efforts need to be contributed to delineating the impact of intrinsic properties of nanoparticles such as material composition, morphology, size distribution, charge, and stiffness in manipulating immune responses in cancer therapy. PMID- 27411559 TI - Positive effects of medical staffing on readmission within 30 days after discharge: a retrospective analysis of obstetrics and gynecology data. AB - BACKGROUND: Improving quality of care is a major healthcare goal; however, the relationship between limited resources and appropriate healthcare distribution has always been problematic. Planning for resource shortages is important for improving healthcare quality. The aim of our study was to evaluate the effects of manpower planning on improvements in quality of care by estimating the effects of medical staffing on readmission within 30 days after discharge. METHODS: We conducted an observational study using 2011-14 National Health Claim data from 692 hospitals and 633 461 admissions. The database included information on uterine (including adnexa) procedures (195 270 cases) and cesarean deliveries (438 191 cases). The outcome variable was readmission within 30 days after discharge. A generalized estimating equation model was used to evaluate associations between readmission and medical staffing. RESULTS: The number of doctors and the proportion of registered nurses (RNs) were significantly associated with a lower risk of readmission within 30 days (proportion of RNs, Relative Risk (RR): 0.97, P values: 0.0025; number of doctors, RR: 0.96, P values: <0.0001). The number of nurses (RNs + licensed practical nurses) was not associated with readmission within 30 days (RR: 1.01, P values: <0.0001). CONCLUSION: Our results suggested that higher numbers of doctors and higher proportions of RNs were positively correlated with a lower risk of readmission within 30 days. Human resource planning to solve manpower shortages should carefully consider the qualitative aspects of clinical care and include long-term planning. PMID- 27411560 TI - Selective Oxytrifluoromethylation of Allylamines with CO2. AB - Reported is the first oxy-trifluoromethylation of allylamines with carbon dioxide (CO2 ) using copper catalysis, thus leading to important CF3 -containing 2 oxazolidones. It is also the first time CO2 , a nontoxic and easily available greenhouse gas, has been used to tune the difunctionalization of alkenes from amino- to oxy-trifluoromethylation. Of particular note, this multicomponent reaction is highly chemo-, regio-, and diastereoselective under redox-neutral and mild reaction conditions. Moreover, these reactions feature good functional-group tolerance, broad substrate scope, easy scalability and facile product diversification. The important products could also be formed with either spirocycles or two adjacent tetrasubstituted carbon centers. PMID- 27411555 TI - Nature and Implications of Oxidative and Nitrosative Stresses in Autoimmune Hepatitis. AB - Oxidative and nitrosative stresses can damage cellular membranes, disrupt mitochondrial function, alter gene expression, promote the apoptosis and necrosis of hepatocytes, and increase fibrosis in diverse acute and chronic liver diseases, including autoimmune hepatitis. The objectives of this review are to describe the mechanisms of oxidative and nitrosative stresses in inflammatory liver disease, indicate the pathogenic implications of these stresses in autoimmune hepatitis, and suggest investigational opportunities to develop interventions that counter them. The principal antioxidant defenses, including glutathione production, the activities of antioxidant enzymes, and the release of the nuclear factor erythroid 2-related factor 2, may be inadequate or suppressed by transforming growth factor beta. The generation of reactive oxygen species can intensify nitrosative stress, and this stress may not be adequately modulated by the thioredoxin-thioredoxin reductase system and induce post-translational modifications of proteins that further disrupt hepatocyte function. The unfolded protein response and autophagy may be unable to restore redox stability, meet metabolic demands, and maintain hepatocyte survival. Emerging interventions with highly selective site- and organelle-specific actions may improve outcomes, and they include inhibitors of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide synthase, and transforming growth factor beta. Pharmacological manipulation of nuclear transcription factors may favor expression of antioxidant genes, and stimulation of chaperone proteins within the endoplasmic reticulum and modulation of autophagy may prevent hepatic fibrosis and enhance cell survival. These interventions constitute investigational opportunities to improve the management of autoimmune hepatitis. PMID- 27411561 TI - Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic beta cells. AB - Insulin resistance results from impaired insulin signaling in target tissues that leads to increased levels of insulin required to control plasma glucose levels. The cycle of hyperglycemia and hyperinsulinemia eventually leads to pancreatic cell deterioration and death by a mechanism that is yet unclear. Insulin induces ROS formation in several cell types. Furthermore, death of pancreatic cells induced by oxidative stress could be potentiated by insulin. Here, we investigated the mechanism underlying this phenomenon. Experiments were done on pancreatic cell lines (Min-6, RINm, INS-1), isolated mouse and human islets, and on cell lines derived from nonpancreatic sources. Insulin (100nM) for 24h selectively increased the production of ROS in pancreatic cells and isolated pancreatic islets, but only slightly affected the expression of antioxidant enzymes. This was accompanied by a time- and dose-dependent decrease in cellular reducing power of pancreatic cells induced by insulin and altered expression of several ER stress response elements including a significant increase in Trb3 and a slight increase in iNos The effect on iNos did not increase NO levels. Insulin also potentiated the decrease in cellular reducing power induced by H2O2 but not cytokines. Insulin decreased the expression of MCL-1, an antiapoptotic protein of the BCL family, and induced a modest yet significant increase in caspase 3/7 activity. In accord with these findings, inhibition of caspase activity eliminated the ability of insulin to increase cell death. We conclude that prolonged elevated levels of insulin may prime apoptosis and cell death-inducing mechanisms as a result of oxidative stress in pancreatic cells. PMID- 27411562 TI - ATPgammaS stalls splicing after B complex formation but prior to spliceosome activation. AB - The ATP analog ATPgammaS inhibits pre-mRNA splicing in vitro, but there have been conflicting reports as to which step of splicing is inhibited by this small molecule and its inhibitory mechanism remains unclear. Here we have dissected the effect of ATPgammaS on pre-mRNA splicing in vitro. Addition of ATPgammaS to splicing extracts depleted of ATP inhibited both catalytic steps of splicing. At ATPgammaS concentrations >=0.5 mM, precatalytic B complexes accumulate, demonstrating a block prior to or during the spliceosome activation stage. Affinity purification of the ATPgammaS-stalled B complexes (B(ATPgammaS)) and subsequent characterization of their abundant protein components by 2D gel electrophoresis revealed that B(ATPgammaS) complexes are compositionally more homogeneous than B complexes previously isolated in the presence of ATP. In particular, they contain little or no Prp19/CDC5L complex proteins, indicating that these proteins are recruited after assembly of the precatalytic spliceosome. Under the electron microscope, B(ATPgammaS) complexes exhibit a morphology highly similar to B complexes, indicating that the ATPgammaS-induced block in the transformation of the B to B(act) complex is not due to a major structural defect. Likely mechanisms whereby ATPgammaS blocks spliceosome assembly at the activation stage, including inhibition of the RNA helicase Brr2, are discussed. Given their more homogeneous composition, B complexes stalled by ATPgammaS may prove highly useful for both functional and structural analyses of the precatalytic spliceosome and its conversion into an activated B(act) spliceosomal complex. PMID- 27411563 TI - Sensitive whole mount in situ localization of small RNAs in plants. AB - Small RNAs, such as microRNAs (miRNAs), regulate gene expression and play important roles in many plant processes. Although our knowledge of their biogenesis and mode of action has significantly progressed, we still have comparatively little information about their biological functions. In particular, knowledge about their spatio-temporal expression patterns rely on either indirect detection by use of reporter constructs or labor-intensive direct detection by in situ hybridization on sectioned material. None of the current approaches allows a systematic investigation of small RNA expression patterns. Here, we present a sensitive method for in situ detection of miRNAs and siRNAs in intact plant tissues that utilizes both double-labeled probes and a specific cross-linker. We determined the expression patterns of several small RNAs in diverse plant tissues. PMID- 27411564 TI - A double blind randomised controlled trial comparing standard dose of iron supplementation for pregnant women with two screen-and-treat approaches using hepcidin as a biomarker for ready and safe to receive iron. AB - BACKGROUND: Until recently, WHO recommended daily iron supplementation for all pregnant women (60 mg/d iron combined with 400ug/d folic acid) where anaemia rates exceeded 40 %. Recent studies indicate that this may pose a risk to pregnant women. Therefore, there is a need to explore screen-and-treat options to minimise iron exposure during pregnancy using an overall lower dosage of iron that would achieve equivalent results as being currently recommended by the WHO. However, there is a lack of agreement on how to best assess iron deficiency when infections are prevalent. Here, we test the use of hepcidin a peptide hormone and key regulator of iron metabolism, as a potential index for 'safe and ready to receive' iron. DESIGN/METHODS: This is a 3-arm randomised-controlled proof-of concept trial. We will test the hypothesis that a screen-and-treat approach to iron supplementation using a pre-determined hepcidin cut-off value of <2.5 ng/ml will achieve similar efficacy in preventing iron deficiency and anaemia at a lower iron dose and hence will improve safety. A sample of 462 pregnant women in rural Gambia will be randomly assigned to receive: a) UNU/UNICEF/WHO international multiple micronutrient preparation (UNIMMAP) containing 60 mg/d iron (reference arm); b) UNIMMAP containing 60 mg/d iron but based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not; c) or UNIMMAP containing 30 mg/d iron as in (b) for 12 weeks in rural Gambia. The study will test if the screen-and-treat approach is non-inferior to the reference arm using the primary endpoint of haemoglobin levels at a non-inferiority margin of 0.5 g/dl. Secondary outcomes of adverse effects, compliance and the impact of iron supplementation on susceptibility to infections will also be assessed. DISCUSSION: This trial is expected to contribute towards minimising the exposure of pregnant women to iron that may not be needed and therefore potentially harmful. If the evidence in this study shows that the overall lower dosage of iron is non-inferior to 60 mg/day iron, this may help decrease side-effects, improve compliance and increase safety. The potential for the use of hepcidin for a simple point-of-care (PoC) diagnostic for when it is most safe and effective to give iron may improve maternal health outcomes. TRIAL REGISTRATION: ISRCTN21955180. PMID- 27411566 TI - Harnessing and storing visible light using a heterojunction of WO3 and CdS for sunlight-free catalysis. AB - CdS and WO3 (CdS/WO3) bilayer film electrodes are fabricated to harness solar visible light (lambda > 420 nm) and store photogenerated electrons for possible use during periods of unavailable sunlight. The overall film thickness is approximately 50-60 MUm, while the CdS underlayer is slightly thinner than WO3 owing to a packing effect. The energetics of CdS and WO3 determined by optical and electrochemical analyses enables cascaded electron transfer from CdS to WO3. The open circuit potential (EOCP) of CdS/WO3 under visible light (approximately 0.35 V vs. SCE) is nearly maintained even in the absence of light, with a marginal decrease (~0.15 V) in ~20 h of darkness. Neither CdS nor WO3 alone exhibits such behavior. The electron lifetimes (tau) of CdS and WO3 are each less than 100 s, whereas coupling of the two increases tau to ~2500 s at the EOCP. In the absence of dissolved O2, tau further increases, suggesting that O2 is the primary electron acceptor. In spite of oxic conditions, CdS/WO3 is capable of continuously reducing Cr(6+) to Cr(3+) and Ag(+) to Ag(0) after removal of visible light. The number of utilized (i.e., stored) electrons in the reductions of Cr(6+) and Ag(+) are estimated to be ~1.08 * 10(17) and ~0.87 * 10(17), respectively. The primary role of CdS is to be a visible-light absorber in the 420-565 nm wavelength range, transferring the photogenerated electrons to WO3. The electrons stored in WO3 are gradually released to electron acceptors with suitable redox potentials. PMID- 27411565 TI - The electroacupuncture-induced analgesic effect mediated by 5-HT1, 5-HT3 receptor and muscarinic cholinergic receptors in rat model of collagenase-induced osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is an degenerative disease characterized by chronic joint pain. Complementary and alternative treatment such as acupuncture have been utilized to alleviate pain. The objective of this study was to investigate the analgesic mechanisms of electroacupuncture (EA) in the collagenase-induced osteoarthritis (CIOA) rat model. METHODS: Four weeks after inducing CIOA by injecting collagenase solution into the left knee of 5-week-old male Sprague-Dawley rats, 2 Hz and 100 Hz EA on Zusanli (ST 36) was performed. The analgesic effect of EA was evaluated by the tail flick latency (TFL) and paw pressure threshold (PPT) tests. To investigate the analgesic mechanism, serotonergic and muscarinic cholinergic receptor agonists and antagonists were injected 20 min prior to EA and the resultant changes were evaluated by the TFL and PPT tests. RESULTS: EA on Zusanli (ST 36) demonstrated an analgesic effect in the CIOA rat model. The 2 Hz EA treatment showed a significantly greater analgesic effect than the 100 Hz treatment. The analgesic effect of 2 Hz EA was not strengthened by 5-HT1, 5-HT2, 5-HT3, and muscarinic cholinergic receptor agonist pretreatment, was blocked by 5-HT1, 5-HT3, and muscarinic cholinergic receptor antagonist pretreatment, but not blocked by 5-HT2 receptor antagonist pretreatment. CONCLUSIONS: In the CIOA rat model, EA on Zusanli (ST 36) exhibited analgesic effects, and 2 Hz EA resulted in a significantly greater analgesic effect than 100 Hz EA. The analgesic effect of 2 Hz EA was reduced by pretreatment of 5-HT1 receptor, 5-HT3 receptor and muscarinic cholinergic receptor antagonists. PMID- 27411567 TI - DNA barcoding of formalin-fixed aquatic oligochaetes for biomonitoring. AB - BACKGROUND: Oligochaetes are valuable bioindicators of the quality of watercourse and lake sediments. The morphological identification of aquatic oligochaetes is difficult, prompting the development of new molecular oligochaete indices based on DNA barcoding and Next-generation sequencing of sorted specimens. In general, the samples for DNA barcoding are fixed in absolute ethanol. However, in the case of aquatic oligochaetes, this medium is not appropriate as it can induce a modification of specimen abundances and of the composition of communities. Therefore, we investigated the possibility to amplify and sequence aquatic oligochaetes fixed in formalin for a short time. We performed guanidine extraction and polymerase chain reaction (PCR) amplification/sequencing of the cytochrome c oxydase I (COI) gene on tissue fragments fixed in formalin for different periods of time (from 1 h to 1 week) and in ethanol. RESULTS: The large majority of aquatic oligochaete specimens fixed in formalin for up to 1 week could be successfully amplified and all obtained sequences were of high quality. The amplification and sequencing success rate of formalin-fixed samples and ethanol-fixed samples was similar. These results suggest that formalin fixation of aquatic oligochaete tissues for a short time does not cause serious damages to DNA and inhibit PCR amplification. CONCLUSION: The possibility to fix aquatic oligochaetes with formalin before genetic analyses is very promising for diversity monitoring, for construction of a comprehensive DNA barcode library and for development of an index based on Next-generation sequencing analysis of samples composed of sorted specimens. PMID- 27411568 TI - Hyperthermia and radiotherapy with or without chemotherapy in locally advanced cervical cancer: a systematic review with conventional and network meta-analyses. AB - PURPOSE: A systematic review with conventional and network meta-analyses (NMA) was conducted to examine the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in locally advanced cervix cancer, IIB IVA (LACC). METHODS AND MATERIALS: A total of 217 abstracts were screened from five databases and reported as per PRISMA guidelines. Only randomised trials with HT and RT +/- CT were considered. The outcomes evaluated were complete response (CR), long-term loco-regional control (LRC), patients alive, acute and late grade III/IV toxicities. RESULTS: Eight articles were finally retained. Six randomised trials with HTRT (n = 215) vs. RT (n = 212) were subjected to meta-analysis. The risk difference for achieving CR and LRC was greater by 22% (p < .001) and 23% (p < .001), respectively, with HTRT compared to RT. A non-significant survival advantage of 8.4% with HTRT was noted with no differences in acute or late toxicities. The only HTCTRT vs. RT trial documented a CR of 83.3% vs. 46.7% (risk difference: 36.7%, p = .001). No other end points were reported. Bayesian NMA, incorporating 13 studies (n = 1000 patients) for CR and 12 studies for patients alive (n = 807 patients), comparing HTCTRT, HTRT, CTRT and RT alone, was conducted. The pairwise comparison of various groups showed that HTRTCT was the best option for both CR and patient survival. This was also evident on ranking treatment modalities based on the "surface under cumulative ranking" values. CONCLUSIONS: In LACC, HTRT demonstrates a therapeutic advantage over RT without significant acute or late morbidities. On NMA, HTCTRT appears promising, but needs further confirmation through prospective randomised trials. PMID- 27411569 TI - Health reforms achieved primary goals, says Obama. PMID- 27411571 TI - Prognostic significance of ankle brachial pressure index: A systematic review and meta-analysis. AB - Purpose To synthesize and quantify the excess risk of morbidity and mortality in individuals with low ankle-brachial pressure index. Methods Electronic databases were searched to identify studies investigating morbidity and mortality outcomes in individuals undergoing ankle-brachial pressure index measurement. Meta analysis of the outcomes was performed using fixed- or random-effects models. Uncertainties related to varying follow-up periods among the studies were resolved by meta-analysis of time-to-event outcomes. Results Forty-three observational cohort studies, enrolling 94,254 participants, were selected. A low ankle-brachial pressure index (<0.9) was associated with a significant risk of all-cause mortality (risk ratio: 2.52, 95% CI 2.26-2.82, P < 0.00001); cardiovascular mortality (risk ratio: 2.94, 95% CI 2.72-3.18, P < 0.00001); cerebrovascular event (risk ratio: 2.17, 95% CI 1.90-2.47, P < 0.00001); myocardial infarction (risk ratio: 2.28, 95% CI 2.07-2.51, P < 0.00001); fatal myocardial infarction (risk ratio: 2.81, 95% CI 2.33-3.40, P < 0.00001); fatal stroke (risk ratio: 2.28, 95% CI 1.80-2.89, P < 0.00001); and the composite of myocardial infarction, stroke, and death (risk ratio: 2.29, 95% CI 1.87-2.81, P < 0.00001). Similar findings resulted from analyses of individuals with asymptomatic PAD, individuals with cardiovascular or cerebrovascular co morbidity, and patients with diabetes. Conclusions A low ankle-brachial pressure index is associated with an increased risk of subsequent cardiovascular and cerebrovascular morbidity and mortality. Randomised controlled trials are required to investigate the effectiveness of screening for PAD in asymptomatic and undiagnosed individuals and to evaluate benefits of early treatment of screen detected PAD. PMID- 27411573 TI - Enhanced thermoelectric performance of CdO : Ag nanocomposites. AB - CdO : Ag nanocomposites with metallic Ag nanoparticles embedded in the polycrystalline CdO matrix were synthesized by the solid-state reaction method. The addition of Ag led to increased grain boundaries of CdO and created numerous CdO/Ag interfaces. By incorporating Ag into the CdO matrix, the power factor was increased which was probably due to the carrier energy filtering effect induced by the enhanced energy-dependent scattering of electrons. In addition, reduced thermal conductivity was also achieved by stronger phonon scattering from grain boundaries, CdO/Ag interfaces and Ag nanoparticles. These concomitant effects resulted in enhanced ZT values for all CdO : Ag nanocomposites, demonstrating that the strategy of introducing metallic Ag nanoparticles into the CdO host was very effective in optimizing the thermoelectric performance. PMID- 27411572 TI - National Health Expenditure Projections, 2015-25: Economy, Prices, And Aging Expected To Shape Spending And Enrollment. AB - Health spending growth in the United States for 2015-25 is projected to average 5.8 percent-1.3 percentage points faster than growth in the gross domestic product-and to represent 20.1 percent of the total economy by 2025. As the initial impacts associated with the Affordable Care Act's coverage expansions fade, growth in health spending is expected to be influenced by changes in economic growth, faster growth in medical prices, and population aging. Projected national health spending growth, though faster than observed in the recent history, is slower than in the two decades before the recent Great Recession, in part because of trends such as increasing cost sharing in private health insurance plans and various Medicare payment update provisions. In addition, the share of total health expenditures paid for by federal, state, and local governments is projected to increase to 47 percent by 2025. PMID- 27411570 TI - BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency. AB - Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient. PMID- 27411574 TI - Glucose modulates food-related salience coding of midbrain neurons in humans. AB - Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low-caloric food (LC), high-caloric food (HC), and non-food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment-specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376-4384, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27411575 TI - Synthesis of Hollow Mesoporous Silica Nanorods with Controllable Aspect Ratios for Intracellular Triggered Drug Release in Cancer Cells. AB - Here, we have reported a straightforward and effective synthetic strategy for synthesis of aspect-ratios-controllable mesoporous silica nanorods with hollow structure (hMSR) and its application for transcription factor (TF)-responsive drug delivery intracellular. Templating by an acid-degradable nickel hydrazine nanorods (NHNT), we have first synthesized the hollow dense silica nanorods and then coated on a mesoporous silica layer. Subsequently, the dense silica layer was removed by the surface-protected etching method and the hollow structure of hMSR was finally formed. The aspect ratios of the hMSR can be conveniently controlled by regulating the aspect ratios of NHNT. Four different hMSR with aspect ratios of ca. 2.5, ca. 5.3, ca. 8.1, and ca. 9.0 has been obtained. It was demonstrated that the as-prepared hMSRs have good stability, high drug loading capacity, and fast cell uptake capability, which makes them to a potential nanocarrier for drug delivery. As the paradigm, hMSR with an aspect ratio of ca. 8.1 was then applied for TF-responsive intracellular anticancer drug controlled release by using a Ag(+)-stabilized molecular switch of triplex DNA (TDNA) as capping agents and probes for TFs recognition. In the presence of TF, the pores of hMSR can be unlocked by the TFs induced disassembly of TDNA, leading to the leakage of DOX. The research in vitro displayed that this system has a TFs triggered DOX release, and the cytotoxicity in L02 normal cells was lower than that of HeLa cells. We hope that this developed hMSR-based system will promote the development of cancer therapy in related fields. PMID- 27411576 TI - Polar Spinel-Perovskite Interfaces: an atomistic study of Fe3O4(111)/SrTiO3(111) structure and functionality. AB - Atomic resolution scanning transmission electron microscopy and electron energy loss spectroscopy combined with ab initio electronic calculations are used to determine the structure and properties of the Fe3O4(111)/SrTiO3(111) polar interface. The interfacial structure and chemical composition are shown to be atomically sharp and of an octahedral Fe/SrO3 nature. Band alignment across the interface pins the Fermi level in the vicinity of the conduction band of SrTiO3. Density functional theory calculations demonstrate very high spin-polarization of Fe3O4 in the interface vicinity which suggests that this system may be an excellent candidate for spintronic applications. PMID- 27411578 TI - Molecular Subtypes of Non-muscle Invasive Bladder Cancer. AB - In this issue of Cancer Cell, Hedegaard et al. report a comprehensive multi center transcriptional analysis of non-muscle invasive urothelial bladder cancer. They describe three molecular subtypes similar to those seen in other cohorts, as well as a unique CIS signature associated with risk of progression to muscle invasive cancer. PMID- 27411579 TI - Context, Context, Context: New Gene Programs Linked to Bad Behavior in MLL-AF9 Initiated Leukemia. AB - In this issue of Cancer Cell, Stavropoulou et al. report that expression of the MLL-AF9 fusion results in acute myelogenous leukemia (AML) with different behaviors depending on cell context, which leads them to identify a transcriptional signature surprisingly resembling that of the epithelial-to mesenchymal (EMT) transition, correlating with aggressiveness of disease. PMID- 27411580 TI - Antagonizing Self-Renewal in Acute Myeloid Leukemia: ID2 Takes the Stage. AB - E proteins and their functional antagonists, the ID proteins, have significant roles in normal hematopoiesis. In this issue of Cancer Cell, Ghisi et al. show that high ID2 levels antagonize self-renewal and promote differentiation of leukemic stem cells in the MLL-translocated molecular subtype of acute myeloid leukemia. PMID- 27411581 TI - RIPK3 Slams the Brake on Leukemogenesis. AB - Evasion of cell death is a key hallmark of cancers. In this issue of Cancer Cell, Hockendorf and colleagues identified RIPK3, an essential kinase for necroptosis, as having a key role in inhibiting acute myeloid leukemia development. PMID- 27411582 TI - Modeling the Epigenetic Chain Reaction Downstream of DNMT3A(R882H). AB - In this issue of Cancer Cell, Lu et al. use a mouse model of DNMT3A(R882H)/NRAS(G12D) acute myeloid leukemia to define a cascade of chromatin changes that emanate from DNMT3A-bound enhancers to initiate disease. The authors also reveal a chemical strategy to interrupt this process. PMID- 27411583 TI - Tumor-Associated Neutrophils Show Phenotypic and Functional Divergence in Human Lung Cancer. AB - Studies in murine cancer models have demonstrated the phenotypic and functional divergence of neutrophils; however, their role in pro- or anti-tumor responses in human remains elusive. In this issue of Cancer Cell, Singhal et al. report the existence of specialized subsets of neutrophils in human lung cancer with diverging functions. PMID- 27411584 TI - Hunger Pains: Stimulating the Appetite of the Immune System for Cancer. AB - In this issue, Pietrocola et al. and Di Biase et al. independently demonstrate that caloric restriction from fasting and pharmacologic inhibition results in an enhanced immunogenic response leading to reduced tumor growth. These two studies provide an exciting connection between the emerging fields of cancer and immune metabolism. PMID- 27411585 TI - P(URI)fying Novel Drivers of NASH and HCC: A Feedforward Loop of IL17A via White Adipose Tissue. AB - How obesity and metabolic syndrome trigger non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains elusive. In this issue, Gomes and colleagues describe that nutrient surplus induces hepatic URI expression, triggering genotoxicity and IL17A expression, thus leading to insulin resistance, NASH, and HCC. IL17A signaling blockers might become a readily translatable therapy. PMID- 27411586 TI - The Multifaceted Role of Perivascular Macrophages in Tumors. AB - Evidence has emerged for macrophages in the perivascular niche of tumors regulating important processes like angiogenesis, various steps in the metastatic cascade, the recruitment and activity of other tumor-promoting leukocytes, and tumor responses to frontline therapies like irradiation and chemotherapy. Understanding the mechanisms controlling the recruitment, retention, and function of these cells could identify important targets for anti-cancer therapeutics. PMID- 27411587 TI - RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells. AB - Since acute myeloid leukemia (AML) is characterized by the blockade of hematopoietic differentiation and cell death, we interrogated RIPK3 signaling in AML development. Genetic loss of Ripk3 converted murine FLT3-ITD-driven myeloproliferation into an overt AML by enhancing the accumulation of leukemia initiating cells (LIC). Failed inflammasome activation and cell death mediated by tumor necrosis factor receptor caused this accumulation of LIC exemplified by accelerated leukemia onset in Il1r1(-/-), Pycard(-/-), and Tnfr1/2(-/-) mice. RIPK3 signaling was partly mediated by mixed lineage kinase domain-like. This link between suppression of RIPK3, failed interleukin-1beta release, and blocked cell death was supported by significantly reduced RIPK3 in primary AML patient cohorts. Our data identify RIPK3 and the inflammasome as key tumor suppressors in AML. PMID- 27411588 TI - Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. AB - Immune-based interventions are promising strategies to achieve long-term cancer free survival. Fasting was previously shown to differentially sensitize tumors to chemotherapy while protecting normal cells, including hematopoietic stem and immune cells, from its toxic side effects. Here, we show that the combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells and cytotoxic CD8(+) tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma progression. In breast tumors, this effect is partially mediated by the downregulation of the stress-responsive enzyme heme oxygenase-1 (HO-1). These data indicate that FMD cycles combined with chemotherapy can enhance T cell dependent targeted killing of cancer cells both by stimulating the hematopoietic system and by enhancing CD8(+)-dependent tumor cytotoxicity. PMID- 27411590 TI - Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma. AB - Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via T helper 17 (Th17) lymphocytes and interleukin 17A (IL-17A). This induces white adipose tissue neutrophil infiltration mediating insulin resistance (IR) and fatty acid release, stored in liver as triglycerides, causing NASH. NASH and subsequently HCC are prevented by pharmacological suppression of Th17 cell differentiation, IL-17A blocking antibodies, and genetic ablation of the IL-17A receptor in myeloid cells. Human hepatitis, fatty liver, and viral hepatitis associated HCC exhibit increased IL-17A correlating positively with steatosis. IL 17A blockers may prevent IR, NASH, and HCC in high-risk patients. PMID- 27411589 TI - Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. AB - Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID- 27411591 TI - Treatment of acute pulmonary embolism with dabigatran versus warfarin. A pooled analysis of data from RE-COVER and RE-COVER II. AB - Dabigatran was non-inferior to warfarin for prevention of recurrent venous thromboembolism (VTE), and dabigatran had a lower rate of bleeding compared with warfarin in two large-scale randomised trials, RE-COVER and RE-COVER II. In this study, we investigate the efficacy and safety of dabigatran versus warfarin according to the index event that qualified the patient for enrollment, either symptomatic pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), or DVT alone. We then analyse the anticoagulant effect of dabigatran vs warfarin on patients enrolled with PE. The pooled dataset for the efficacy analysis consisted of 2553 and 2554 patients who were randomised to dabigatran and warfarin, respectively. Recurrent VTE/VTE-related death during the study period and additional 30-day follow-up occurred in 2.7 % of all patients on dabigatran and in 2.4 % on warfarin (hazard ratio [HR] 1.09 [95 % confidence interval 0.77, 1.54]). In patients with PE as their index event, recurrent VTE/VTE-related death occurred in 2.9 % vs 3.1 % of patients (HR 0.93 [0.53, 1.64]). There were significantly fewer major bleeding events in patients treated with dabigatran than with warfarin (HR 0.60 [0.36, 0.99]). The pattern was similar both in patients with PE and in those with DVT alone as the index event. These analyses of the pooled dataset from the RE-COVER and RE-COVER II trials indicate that dabigatran is as effective as warfarin in preventing recurrent VTE, regardless of whether patients present with symptomatic PE (with or without DVT) or with symptomatic DVT alone. Dabigatran was also associated with a lower risk of bleeding than warfarin, regardless of the index event. PMID- 27411592 TI - Ruthenium(0)-catalyzed hydroarylation of alkynes via ketone-directed C-H functionalization using in situ-generated ruthenium complexes. AB - A versatile method for the Ru(0)-catalyzed hydroarylation of alkynes using weakly coordinating ketones enabled by the in situ generation of a Ru(0) catalyst from an air-stable, inexpensive and user-friendly Ru(ii) precatalyst is reported for the first time. The method provides straightforward access to a wide range of functionalized ketone building blocks that would be difficult to access by conventional methods. Most crucially, this report demonstrates for the first time that the in situ generated Ru(0) catalysts advance the classic Ru(0)-catalyzed C H functionalization platform to substrates that would otherwise be unreactive. Product manipulation and mechanistic studies are reported. PMID- 27411593 TI - Uplift-driven sediment redness decrease at ~16.5 Ma in the Yumen Basin along the northeastern Tibetan Plateau. AB - Significant climate shifts in the northeastern Tibetan Plateau have taken place during the Cenozoic, but the reasons behind them remain unclear. In order to unravel the mechanisms driving these climate changes, proxy data with accurate age constraint are needed. Here we present magnetostratigraphy, sediment color (redness a*, and lightness L*) and grain-size analysis from an early to middle Miocene (~20-15.3 Ma) sediment sequence preserved in the Yumen Basin on the northeastern Tibetan Plateau. In this basin, remarkable increase in lightness, decreases in redness and in ratio of hematite (Hm) to goethite (Gt) took place at ~16.5 Ma. We suggest that these changes result from shorter duration of weathering, climatic wetting, and cooling associated with rapid uplift of the Qilian Shan at the middle Miocene. PMID- 27411594 TI - Homogeneity and elemental distribution in self-assembled bimetallic Pd-Pt aerogels prepared by a spontaneous one-step gelation process. AB - Multi-metallic aerogels have recently emerged as a novel and promising class of unsupported electrocatalyst materials due to their high catalytic activity and improved durability for various electrochemical reactions. Aerogels can be prepared by a spontaneous one-step gelation process, where the chemical co reduction of metal precursors and the prompt formation of nanochain-containing hydrogels, as a preliminary stage for the preparation of aerogels, take place. However, detailed knowledge about the homogeneity and chemical distribution of these three-dimensional Pd-Pt aerogels at the nano-scale as well as at the macro scale is still unclear. Therefore, we used a combination of spectroscopic and microscopic techniques to obtain a better insight into the structure and elemental distribution of the various Pd-rich Pd-Pt aerogels prepared by the spontaneous one-step gelation process. Synchrotron-based extended X-ray absorption fine structure (EXAFS) spectroscopy and high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM) in combination with energy-dispersive X-ray spectroscopy (EDX) were employed in this work to uncover the structural architecture and chemical composition of the various Pd-rich Pd-Pt aerogels over a broad length range. The Pd80Pt20, Pd60Pt40 and Pd50Pt50 aerogels showed heterogeneity in the chemical distribution of the Pt and Pd atoms inside the macroscopic nanochain-network. The features of mono-metallic clusters were not detected by EXAFS or STEM-EDX, indicating alloyed nanoparticles. However, the local chemical composition of the Pd-Pt alloys strongly varied along the nanochains and thus within a single aerogel. To determine the electrochemically active surface area (ECSA) of the Pd-Pt aerogels for application in electrocatalysis, we used the electrochemical CO stripping method. Due to their high porosity and extended network structure, the resulting values of the ECSA for the Pd-Pt aerogels were higher than that for a commercially available unsupported Pt black catalyst. We show that the Pd-Pt aerogels possess a high utilization of catalytically active centers for electrocatalytic applications based on the nanostructured bimetallic framework. Knowledge about the homogeneity and chemical distribution of the bimetallic aerogels can help to further optimize their preparation by the spontaneous one-step gelation process and to tune their electrocatalytic reactivity. PMID- 27411595 TI - How China is rewriting the book on human origins. PMID- 27411596 TI - The people who don't get 'Eleanor Rigby'. PMID- 27411597 TI - Researchers and policymakers are now free to tackle the most-pressing GM issues. PMID- 27411598 TI - Fifty shades of pain. PMID- 27411599 TI - Watch out for cheats in citation game. PMID- 27411611 TI - South Africa's political turmoil endangers research. PMID- 27411612 TI - Mobile-phone expansion could disrupt key weather satellites. PMID- 27411613 TI - Brain-data gold mine could reveal how neurons compute. PMID- 27411614 TI - Beat it, impact factor! Publishing elite turns against controversial metric. PMID- 27411615 TI - Germany's renewable revolution awaits energy forecast. PMID- 27411616 TI - Corrections. PMID- 27411617 TI - South Africa ushers in a new era for HIV. PMID- 27411618 TI - Policy: Five cornerstones of a global bioeconomy. PMID- 27411619 TI - Policy: Marine biodiversity needs more than protection. PMID- 27411621 TI - Industrial waste: Citizens arrest river pollution in China. PMID- 27411622 TI - Biodiversity: Speed restoration of EU ecosystems. PMID- 27411623 TI - Brain drain: Entice Africa's scientists to stay. PMID- 27411624 TI - Pyrogeography: Build social costs into wildfire risk. PMID- 27411625 TI - Politics: Israel must release Palestinian physicist. PMID- 27411626 TI - Jerome Bruner (1915-2016). PMID- 27411627 TI - Materials science: Magnetic nanoparticles line up. PMID- 27411628 TI - Astrophysics: Variable snow lines affect planet formation. PMID- 27411629 TI - Metrology: Schrodinger's cat beats a quantum limit. PMID- 27411630 TI - Correction. PMID- 27411631 TI - Imaging the water snow-line during a protostellar outburst. AB - A snow-line is the region of a protoplanetary disk at which a major volatile, such as water or carbon monoxide, reaches its condensation temperature. Snow lines play a crucial role in disk evolution by promoting the rapid growth of ice covered grains. Signatures of the carbon monoxide snow-line (at temperatures of around 20 kelvin) have recently been imaged in the disks surrounding the pre-main sequence stars TW Hydra and HD163296 (refs 3, 10), at distances of about 30 astronomical units (au) from the star. But the water snow-line of a protoplanetary disk (at temperatures of more than 100 kelvin) has not hitherto been seen, as it generally lies very close to the star (less than 5 au away for solar-type stars). Water-ice is important because it regulates the efficiency of dust and planetesimal coagulation, and the formation of comets, ice giants and the cores of gas giants. Here we report images at 0.03-arcsec resolution (12 au) of the protoplanetary disk around V883 Ori, a protostar of 1.3 solar masses that is undergoing an outburst in luminosity arising from a temporary increase in the accretion rate. We find an intensity break corresponding to an abrupt change in the optical depth at about 42 au, where the elevated disk temperature approaches the condensation point of water, from which we conclude that the outburst has moved the water snow-line. The spectral behaviour across the snow-line confirms recent model predictions: dust fragmentation and the inhibition of grain growth at higher temperatures results in soaring grain number densities and optical depths. As most planetary systems are expected to experience outbursts caused by accretion during their formation, our results imply that highly dynamical water snow-lines must be considered when developing models of disk evolution and planet formation. PMID- 27411632 TI - A sensitive electrometer based on a Rydberg atom in a Schrodinger-cat state. AB - Fundamental quantum fluctuations caused by the Heisenberg principle limit measurement precision. If the uncertainty is distributed equally between conjugate variables of the meter system, the measurement precision cannot exceed the standard quantum limit. When the meter is a large angular momentum, going beyond the standard quantum limit requires non-classical states such as squeezed states or Schrodinger-cat-like states. However, the metrological use of the latter has been so far restricted to meters with a relatively small total angular momentum because the experimental preparation of these non-classical states is very challenging. Here we report a measurement of an electric field based on an electrometer consisting of a large angular momentum (quantum number J ~ 25) carried by a single atom in a high-energy Rydberg state. We show that the fundamental Heisenberg limit can be approached when the Rydberg atom undergoes a non-classical evolution through Schrodinger-cat states. Using this method, we reach a single-shot sensitivity of 1.2 millivolts per centimetre for a 100 nanosecond interaction time, corresponding to 30 microvolts per centimetre per square root hertz at our 3 kilohertz repetition rate. This highly sensitive, non invasive space- and time-resolved field measurement extends the realm of electrometric techniques and could have important practical applications: detection of individual electrons in mesoscopic devices at a distance of about 100 micrometres with a megahertz bandwidth is within reach. PMID- 27411633 TI - Self-assembly of graphene ribbons by spontaneous self-tearing and peeling from a substrate. AB - Graphene and related two-dimensional materials have shown unusual and exceptional mechanical properties, with similarities to origami-like paper folding and kirigami-like cutting demonstrated. For paper analogues, a critical difference between macroscopic sheets and a two-dimensional solid is the molecular scale of the thin dimension of the latter, allowing the thermal activation of considerable out-of-plane motion. So far thermal activity has been shown to produce local wrinkles in a free graphene sheet that help in theoretically understanding its stability, for example, and give rise to unexpected long-range bending stiffness. Here we show that thermal activation can have a more marked effect on the behaviour of two-dimensional solids, leading to spontaneous and self-driven sliding, tearing and peeling from a substrate on scales approaching the macroscopic. We demonstrate that scalable nanoimprint-style contact techniques can nucleate and direct the parallel self-assembly of graphene ribbons of controlled shape in ambient conditions. We interpret our observations through a simple fracture-mechanics model that shows how thermodynamic forces drive the formation of the graphene-graphene interface in lieu of substrate contact with sufficient strength to peel and tear multilayer graphene sheets. Our results show how weak physical surface forces can be harnessed and focused by simple folded configurations of graphene to tear the strongest covalent bond. This effect may hold promise for the patterning and mechanical actuating of devices based on two dimensional materials. PMID- 27411634 TI - Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification. AB - Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers. Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro. PMID- 27411637 TI - Seeds of neuroendocrine doubt. PMID- 27411635 TI - Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios. AB - The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described as being expressed in uncommitted cell populations. This led to the assumption that lineage choice is cell-intrinsically initiated and determined by stochastic switches of randomly fluctuating cross-antagonistic transcription factors. However, this hypothesis was developed on the basis of RNA expression data from snapshot and/or population-averaged analyses. Alternative models of lineage choice therefore cannot be excluded. Here we use novel reporter mouse lines and live imaging for continuous single-cell long-term quantification of the transcription factors GATA1 and PU.1 (also known as SPI1). We analyse individual haematopoietic stem cells throughout differentiation into megakaryocytic erythroid and granulocytic-monocytic lineages. The observed expression dynamics are incompatible with the assumption that stochastic switching between PU.1 and GATA1 precedes and initiates megakaryocytic-erythroid versus granulocytic monocytic lineage decision-making. Rather, our findings suggest that these transcription factors are only executing and reinforcing lineage choice once made. These results challenge the current prevailing model of early myeloid lineage choice. PMID- 27411638 TI - Collinge et al. reply. PMID- 27411640 TI - Use and limitations of prognostic models for the critically ill. PMID- 27411641 TI - Reactive Oxygen Species: Physical, Chemical, and Biological Structures based on ROS-Sensitive Moieties that are Able to Respond to Oxidative Microenvironments (Adv. Mater. 27/2016). AB - On page 5553, C. Tapeinos and A. Pandit review the properties of reactive oxygen species (ROS)-sensitive moieties which can respond to oxidative conditions inside cells. ROS-sensitive chemical structures, shown in the background of the image, are currently used in the biomedical field as drug-delivery systems, imaging probes, prochelators, and prodrugs for imaging and treatment of various diseases. PMID- 27411639 TI - Serotype IV Streptococcus agalactiae ST-452 has arisen from large genomic recombination events between CC23 and the hypervirulent CC17 lineages. AB - Streptococcus agalactiae (Group B Streptococcus, GBS) causes life-threatening infections in newborns and adults with chronic medical conditions. Serotype IV strains are emerging both among carriers and as cause of invasive disease and recent studies revealed two main Sequence Types (STs), ST-452 and ST-459 assigned to Clonal Complexes CC23 and CC1, respectively. Whole genome sequencing of 70 type IV GBS and subsequent phylogenetic analysis elucidated the localization of type IV isolates in a SNP-based phylogenetic tree and suggested that ST-452 could have originated through genetic recombination. SNPs density analysis of the core genome confirmed that the founder strain of this lineage originated from a single large horizontal gene transfer event between CC23 and the hypervirulent CC17. Indeed, ST-452 genomes are composed by two parts that are nearly identical to corresponding regions in ST-24 (CC23) and ST-291 (CC17). Chromosome mapping of the major GBS virulence factors showed that ST-452 strains have an intermediate yet unique profile among CC23 and CC17 strains. We described unreported large recombination events, involving the cps IV operon and resulting in the expansion of serotype IV to CC23. This work sheds further light on the evolution of GBS providing new insights on the recent emergence of serotype IV. PMID- 27411643 TI - Materials Science in Ireland - Current Developments and Future Aspirations. PMID- 27411645 TI - Nanoparticle Assemblies: Nanoparticle Clusters: Assembly and Control Over Internal Order, Current Capabilities, and Future Potential (Adv. Mater. 27/2016). AB - Clusters or assemblies of nanoparticles exhibit unique features which arise from the enhancement of properties of single nanoparticles or due to new collective properties. On page 5400, D. F. Brougham and co-workers review the role of nanoparticle interactions in controlling cluster formation, and classify the assembly mechanisms. Emerging applications for surface-enhanced Raman scattering (SERS), optical labeling, light harvesting, magnetic resonance imaging (MRI), hyperthermia, photocatalysis, enrichment, and separation are presented. Cover image by Christoph Hohmann, Nanosystems Initiative Munich (NIM). PMID- 27411644 TI - Nanoparticle Clusters: Assembly and Control Over Internal Order, Current Capabilities, and Future Potential. AB - The current state of the art in the use of colloidal methods to form nanoparticle assemblies, or clusters (NPCs) is reviewed. The focus is on the two-step approach, which exploits the advantages of bottom-up wet chemical NP synthesis procedures, with subsequent colloidal destabilization to trigger assembly in a controlled manner. Recent successes in the application of functional NPCs with enhanced emergent collective properties for a wide range of applications, including in biomedical detection, surface enhanced Raman scattering (SERS) enhancement, photocatalysis, and light harvesting, are highlighted. The role of the NP-NP interactions in the formation of monodisperse ordered clusters is described and the different assembly processes from a wide range of literature sources are classified according to the nature of the perturbation from the initial equilibrium state (dispersed NPs). Finally, the future for the field and the anticipated role of computational approaches in developing next-generation functional NPCs are briefly discussed. PMID- 27411647 TI - Priorities for oral and dental research. PMID- 27411648 TI - Burden of oral diseases: Further thoughts. PMID- 27411649 TI - Systemic absorption of 0.1% triamcinolone acetonide as topical application in management of oral lichen planus. AB - CONTEXT: Topical corticosteroids are the treatment of choice for oral lichen planus (OLP) due to its potential anti-inflammatory effect. However, chronic nature of OLP often requires long-term and frequent applications, exposing patients to local and systemic side effects. AIM: To detect the systemic absorption of 0.1% triamcinolone acetonide (TAC) through the oral mucosa of patients with OLP. SUBJECTS AND METHODS: This was a pilot pharmacokinetic study carried out in the Department of Oral Medicine and Radiology in collaboration with the Department of Toxicology, over 10 months. A total of twenty patients with OLP were included and advised to apply 0.1% TAC 3 times/day for 2 weeks and 2 times/day for next 2 weeks. Blood samples were obtained on the first and second visits and analyzed for triamcinolone using High pressure liquid chromatography (HPLC). STATISTICAL ANALYSIS USED: Paired t-test was done to compare visual analog scale (VAS) score for burning sensation at the first and second visits, statistically significant if P < 0.05. The baseline demographic data were analyzed using descriptive statistics. RESULTS: Paired t-test was done to compare VAS score for burning sensation at the first and second visits, which turned to being statistically significant (P = 0.001). Although HPLC is an established method for the detection of TAC, none of the study populations showed evidence of steroid (TAC) in the blood sample during 4 weeks of treatment duration. CONCLUSIONS: 0.1% triamcinolone is a relatively safe drug to be used with no systemic absorption in the standard dose regimen for oral lichen palnus. PMID- 27411650 TI - A risk assessment study on work-related musculoskeletal disorders among dentists in Bhopal, India. AB - BACKGROUND: Work-related musculoskeletal disorders (WMSDs) are responsible for morbidity in many working populations, which are of multifactorial in origin and of global concern due to industrialization. Dentists as one of the health-care professionals are prone to develop these WMSDs. The study aims to determine the prevalence of WMSDs among dentists in Bhopal region and explores the various risk factors for the development of MSDs and WMSDs. MATERIALS AND METHODS: This proposed study is a cross-sectional study conducted among dentists of two randomly selected dental colleges of Bhopal, India. A structured questionnaire was used to collect the demographic information, occupational history, risk factors, and ergonomic awareness with job task details. Prevalidated standardized tools such as quick exposure check list, rapid entire body assessment score sheet, and Nordic Musculoskeletal Questionnaire were also used. Data were entered in MS-Excel and analyzed through SPSS version 18. RESULTS: More than 92% of the participants reported pain and discomfort in at least one part of their body. The major affected body part is neck, followed by the lower back and wrist. More than half of the orthodontists and oral surgeons reported that their MSDs are work related origin. Pearson's correlation test indicated that there is a positive correlation between the current exposure and risk (r = 0.613). Multivariate regression analysis found that younger participants, male (OR = 4.1), involved physical activity (OR = 1.04), dentists not taught about ergonomics in their dental school (OR = 1.69) or never attended any workshops (OR = 1.38), who reported task involving sustained muscle contraction (OR = 1.12) or task with repetitive movements (OR = 1.11) are the major risk factors for the development of MSDs among the dentists. CONCLUSION: This risk assessment study found that there is a high prevalence of MSDs and WMSDs among dentists. Ergonomic awareness and health promotion need to be integrated with the professional practice for dentists. PMID- 27411651 TI - Morphological analysis of collagen and elastic fibers in oral squamous cell carcinoma using special stains and comparison with Broder's and Bryne's grading systems. AB - OBJECTIVES: Morphologic detection of connective tissue fiber changes in oral squamous cell carcinoma (OSCC) using special stains remains less documented. The aims of the present study were to study the collagen and elastic fibers in different stages of OSCC and to correlate these changes with two grading systems Broder's and Bryne's. STUDY DESIGN: Forty-eight cases of OSCC were studied using hematoxylin and eosin, Verhoeff's - Van Gieson stain for elastic fibers and picrosirius red stain for collagen fibers. The changes were compared with all the grades of carcinoma. Normal mucosa was taken as control. RESULTS: Statistical analysis using Chi-square and ANOVA, showed significant association between the grades of carcinoma and extracellular matrix changes. Greenish-yellow collagen fibers were found to be significantly increased in the poorly differentiated/Grade 3 cases (P< 0.0001) where as well-differentiated/Grade 1 cases showed predominantly reddish-orange and yellowish-orange birefringence of collagen fibers. Chi-square analysis showed a significant amount of fragmented pattern of elastic fibers in poorly differentiated OSCC (chi2 = 104.45, P = 0.009)/Grade 3 OSCC (chi2 = 94.81, P = 0.016). CONCLUSION: The study of the connective tissue stromal changes can be used as an adjunct to histological grading and thereby helping the surgeon to determine the amount of marginal clearance. PMID- 27411652 TI - Evaluation of dentine hypersensitivity in adult population with chronic periodontitis visiting dental hospital in Chandigarh. AB - BACKGROUND: Periodontal attachment loss could be an earlier indicator or a possible risk factor of dentine hypersensitivity (DH). Thus, there is a need for diagnosing this condition both by questionnaire and by clinical examination before rendering both home care and in-office treatment modalities. AIMS: To investigate the relationship between various demographic factors and DH and to detect the percentage of patients using desensitizing agents. MATERIALS AND METHODS: In this cross-sectional study, 2051 patients were evaluated till the required sample size of 1000 patients was achieved who were evaluated both by questionnaire and clinical test. Association between DH clinical attachment level and apparent recession was established. RESULTS: This study found that the prevalence of dentine hypersensitivity in chronic periodontitis patients was 37.2% according to questionnaire and 47.8% according to the results of clinical test. Various demographic factors were found to affect dentine hypersensitivity such as age, gender, education, diet, and locality. CONCLUSION: The prevalence of dentine hypersensitivity in chronic periodontitis patients was 37.2% according to questionnaire and 47.8% according to the results of clinical test. Periodontal attachment loss could be an earlier indicator or a possible risk factor of DH. Only 14.36% of the patients with sensitive teeth used desensitizing paste. This could be due to the fact that either the patients did not consider the condition bad enough to warrant treatment or it was not being diagnosed. PMID- 27411653 TI - Assessment of interns and postgraduate dental student's knowledge regarding equipment ergonomics. AB - CONTEXT: The substantial knowledge concerning ergonomics and its practical application is vital for forestalling musculoskeletal disorders. The role of equipment ergonomics (EE) in preventing these work-related ailments is significantly noteworthy. AIM: The aim of the study was to assess the prevailing perception of postgraduates (PGs) and interns regarding EE and preparing the Indian dental workforce for the challenges of India's growing economy and population. SETTINGS AND DESIGN: Authors conducted a cross-sectional survey between December 2013 and February 2014 amidst the interns and PG dental students of Davangere city, Karnataka, India. SUBJECTS AND METHODS: The data were collected using 21-item custom designed proforma, comprising of questions evaluating student's basic knowledge about EE. STATISTICAL ANALYSIS USED: Statistical analysis was done using Chi-square test in each group (PGs and interns) and Mann-Whitney test was implemented for comparison between both groups. RESULTS: Of 358 subjects surveyed, 48% PGs and 52% interns affirmed that they came across EE only through this survey. In addition, 91.18% of PGs and 90.59% interns believed that the accentuation on EE is less in the current dental curriculum. CONCLUSIONS: Comprehensive understanding and practical application of EE among the participants was found to be lacking. The importance of microbreaks and chair side exercises should be emphasized and training should be initiated at an early stage before improper postural habits develop. PMID- 27411654 TI - An institutional survey for knowledge-based and self-awareness assessment in temporomandibular joint disorders among dental students. AB - CONTEXT: Temporomandibular joint disorders (TMDs) have been recognized as one of the most common causes of nondental orofacial pain. Various studies have been reported in literature regarding the relationship between prevalence of signs and symptoms of TMDs and gender, suggestive of female predilection; however, none of the studies have yet been reported to suggest the relationship between knowledge about temporomandibular joint (TMJ) and TMDs and self-awareness of its signs and symptoms. AIM: To find a relationship between the level of knowledge about TMJ and TMDs and self-awareness of its signs and symptoms. SETTINGS AND DESIGN: This study was designed as an institutional survey. The study sample comprised 491 undergraduate and postgraduate (PG) students, consisting of 90 males and 401 females with age ranging between 18 and 32 years. SUBJECTS AND METHODS: Two sets of questionnaire were distributed among the students. STATISTICAL ANALYSIS USED: Statistical analysis was performed with the help of Epi Info (TM) 3.5.3, descriptive statistical analysis, test of proportion, Chi-square test, one-way analysis of variance, Tukey's test, and knowledge index. RESULTS: It was observed that there was a gradual increase in the level of knowledge about TMJ and TMDs and self-awareness of its signs and symptoms from the 1st year to PG students. CONCLUSIONS: A direct relationship exists between the level of knowledge about TMJ and TMDs and self-awareness of its signs and symptoms. PMID- 27411655 TI - Using smartphone video "selfies" to monitor change in toothbrushing behavior after a brief intervention: A pilot study. AB - BACKGROUND: Attempts to refine toothbrushing (TB) technique, an ingrained habit in adults, can meet with some challenges. Recently, the role of proactive interference as a barrier to improving the learning of proper brushing has been proposed. This pilot feasibility study was designed to investigate TB behavior and to see how it changes after training. Smartphone video "selfies" (SPVSs) are increasingly being used in the medical field to assess, monitor, and determine the progression of diseases. MATERIALS AND METHODS: We used SPVS to study TB skills in a small sample of volunteers. Over a period of 14 days, after a one time group training session, we observed TB behavior of volunteers using self captured SPVS. RESULTS: Following the brief intervention, we observed an 8% of improvement in TB skills. DISCUSSION: To the best of our knowledge, this is the first report using SPVS to study TB behavior. We demonstrated initial feasibility of using SPVS in the dental setting. We observed modest improvements in toothbrushing accuracy and quality, and we generated important experiences about the use of Selfies for TB monitoring and intervention, and some interesting insights about where in the toothbrushing is more or less effective. CONCLUSION: Further investigation using a larger sample size is needed to thoroughly assess the effectiveness of this approach to improve TB skills and better understand the role of proactive interference. PMID- 27411656 TI - Cyclic fatigue resistance of different continuous rotation and reciprocating endodontic systems. AB - OBJECTIVE: The objective of this study is to compare the cyclic fatigue resistance of nine types of endodontic instruments of nickel-titanium. MATERIALS AND METHODS: Five files of 25 mm of length of each group: Reciproc (RC) R25; WaveOne (WO) Primary; Unicone (UC) L25 25/0.06; K3XF 25/0.06; ProTaper Universal F2 (PTF2); ProTaper Next X2 (PTX2); Mtwo 25/0.06; BioRaCe 25/0.06; One Shape L25 25/0.06 were subjected to a cyclic fatigue resistance test on a mechanical apparatus. The mean fracture time was analyzed statistically by one-way analysis of variance and Tukey's honest significant difference post hoc test, with significance set at P< 0.05. CONCLUSION: It was observed that the groups PTX2, RC, R25, UC L25 25/0.06, and WO Primary presented greater cyclic fracture resistance than the other groups (P< 0.001). PMID- 27411657 TI - Indirect immunofluorescence technique to study expression of toll-like receptor 4 in chronic periodontitis. AB - AIM: The aim of this study was to analyze the expression level and localization of Toll-like receptor (TLR) 4 in gingival samples of healthy and chronic periodontitis subjects by indirect immunofluorescence technique (IFT). MATERIALS AND METHODS: In this study, gingival tissue samples were obtained from 25 healthy and 25 periodontitis individuals. The tissues were processed and the initial characterization was done by hematoxylin and eosin staining. The expression and localization of the TLR4 receptor were determined in the epithelial and connective layer cells of the gingival tissue using the indirect IFT. Immunofluorescence images were acquired and quantitative expression of TLRs was analyzed by calculating the percentage of cells showing positive results. RESULTS: We found that the healthy control group exhibited significantly lower values of TLR4 expression in comparison with the periodontitis patients. We also found that in patients with periodontitis the concentration of TLR4 was higher in the epithelium as compared to their expression in connective tissue cells. CONCLUSIONS: These data suggested a definite involvement of TLR4 in initiating and progression of an inflammatory response in periodontitis. PMID- 27411658 TI - Comparative study of sorption and solubility of heat-cure and self-cure acrylic resins in different solutions. AB - OBJECTIVE: The objective of this study was to compare the sorption and solubility of heat-cure and self-cure acrylic resins in different solutions. MATERIALS AND METHODS: One heat-cure acrylic resin (Trevalon) and one self-cure acrylic resin (Rapid Repair) were studied. Five groups of square-shaped specimens (20 mm * 20 mm * 2 mm) were prepared for each acrylic resin and then immersed in five solutions: distilled water, artificial saliva, denture cleansing solution, distilled water, and denture cleaning solution for 12 h alternatively, artificial saliva and denture cleaning solution for 12 h alternatively at 37 +/- 2 degrees C, and tested sorption and solubility by weight gain/loss method, respectively, after 1, 6, and 11 weeks. The data were analyzed by one-way analysis of variance followed by post hoc Tukey's test. RESULTS: Water sorption mean values varied from 17.5 +/- 0.88 to 27.25 +/- 1.04 MUg/mm 3 for heat cure and from 12.75 +/- 0.55 to 19.75 +/- 1.04 MUg/mm 3 for self-cure in the different solutions after different interval periods of 1, 6, and 11 weeks. These values were statistically significant (P< 0.001). Water solubility mean values varied from 0.25 +/- 0.55 to 1.5 +/- 0.55 MUg/mm 3 for heat cure and from 1.5 +/- 0.55 to 6.5 +/- 0.55 MUg/mm 3 for self-cure in the different solutions after different interval periods of 1, 6, and 11 weeks. These values were statistically not significant (P > 0.05). There was no linear correlation between sorption and solubility values. Overall, analysis of results showed the maximum sorption value in denture cleansing solution followed by alternative soaking in distilled water and artificial saliva. Least sorption was observed with artificial saliva followed by distilled water. CONCLUSION: Both heat-cure and self-cure acrylic resins showed varying water sorption and solubility. The results of both water sorption and solubility showed compliance with the International Standards Organization specification. No correlation was found between water sorption and solubility. Artificial saliva solution is a better storage medium than distilled water and denture cleansing solution for both heat-cure and self-cure acrylic resins. PMID- 27411659 TI - Evaluation of coronal microleakage of mineral trioxide aggregate plug-in teeth with short roots prepared for post placement using bacterial penetration technique. AB - CONTEXT: Two of the problems of the placement of posts in teeth with short roots are to determine the minimum length of the canal obturation material at the apical third of the root canal and removal of all the canal obturation material from the root canal during post space preparation. AIM: The aim of the present study was to compare the coronal microleakage of mineral trioxide aggregate (MTA) plug and gutta-percha in short roots prepared for post placement using the bacterial penetration technique. MATERIALS AND METHODS: In the presentin vitro study, 40 extracted single-rooted anterior teeth measuring 13 mm in root length were selected. Since the roots were short, 3 mm of the root length was allocated to the root canal obturation material and 10 mm of the root length was allocated to post placement. After preparation of the root canals, post spaces were prepared and the samples were randomly divided into two groups of gutta-percha and MTA. Fifteen root canals were obturated with gutta-percha and the post space was immediately prepared, with 3 mm of gutta-percha remaining in the apical end of the root canal. In 15 teeth, MTA plugs were placed, which measured 3 mm in length. The samples were placed in the Enterococcus faecalis bacterial microleakage system for 120 days. The time for the turbidity of each sample was recorded. Data were analyzed with Fisher's exact test. RESULTS: During the study period, turbidity was observed in all the gutta-percha samples and in only four MTA samples, with statistically significant differences between the two groups (P< 0.001). CONCLUSION: Based on the results, MTA exhibited much better sealing ability compared to gutta-percha as a root canal obturation material in teeth with short roots. PMID- 27411660 TI - Antimicrobial effect of platelet-rich plasma and platelet-rich fibrin. AB - CONTEXT: Platelet concentrates have been extensively used in a variety of medical fields to promote soft- and hard-tissue regeneration. The significance behind their use lies in the abundance of growth factors (GFs) in platelets alpha granules that promote wound healing. Other than releasing a pool of GFs upon activation, platelets also have many features that indicate their role in the anti-infective host defense. AIM: The aim of this study is to evaluate the antimicrobial activities of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) against periodontal disease-associated bacteria. SUBJECTS AND METHODS: Blood samples were obtained from ten adult male patients. PRP and PRF were procured using centrifugation. The antimicrobial activity of PRP and PRF was evaluated by microbial culturing using bacterial strains of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. RESULTS: P. gingivalis and A. actinomycetemcomitans were inhibited by PRP but not by PRF. CONCLUSIONS: PRP is a potentially useful substance in the fight against periodontal pathogens. This might represent a valuable property in adjunct to the enhancement of tissue regeneration. PMID- 27411661 TI - Modified endaural approach for the treatment of condylar fractures: A review of 75 cases. AB - BACKGROUND: There are several treatment approaches for mandibular condyle fractures. Type of fracture, clinical experience, and preference of the operating surgeon dictate the approach. Given this highly varied outcome, this manuscript intends to document the treatment experience of 75 patients with extracapsular condyle fractures using author's modification of the traditional endaural approach in the region. MATERIALS AND METHODS: A retrospective chart review was performed on patients with mandibular condylar fractures who visited the author's center between 2004 and 2014. For the surgical reduction and fixation, an endaural (ear) approach via the author's modification of Al-Kayat Bramley's incision in the superficial temporal region was used. Postoperative clinical parameters were evaluated which include the degree of mouth opening, chin deviation during mouth opening, occlusal relationship, temporomandibular joint function, radiographic stability, and other postoperative complications of condylar fractures such as infection, plate fracture, and permanent paralysis of facial nerve. Adolescence/adult patients with unilateral/bilateral condylar fracture who underwent open reduction with the follow-up of at least 1 year were included in the study. Edentulous and patients <15 years who underwent closed treatment were excluded from the study. RESULTS: The study group consisted of 75 cases of mandibular condyle fractures, of which 55 cases were of unilateral condyle fractures and 20 cases were of bilateral condylar fractures. Postoperative follow-up of patients ranged from 1 to 10 years with the mean of 3.04 +/- 1.93 years. The occlusal relationships were excellent in all with the mean degree of mouth opening of 40.11 mm (maximum 4.5 cm and minimum 2.9 cm), of which four patients reported restricted mouth opening. Orthopantomogram and computed tomography showed complete anatomical reduction of the condyle fracture in all patients. Nine out of 75 patients developed transient facial weakness, with no other postoperative complications of condylar fractures such as infections, plate fracture, and permanent paralysis of facial nerve were noted. The overall success rate was 92%. CONCLUSION: Surgery for mandibular condyle fractures with modified approach allows direct vision of the fracture and reduces surgical trauma to the site while avoiding permanent facial nerve injury. Hence, the author's modified Al-Kayat Bramley incision via endaural approach could be considered as the best approach for open reduction and internal fixation of condylar neck and subcondylar mandibular fractures. PMID- 27411662 TI - Evaluation of proximity of mandibular molars and second premolar to inferior alveolar nerve canal among central Indians: A cone-beam computed tomographic retrospective study. AB - CONTEXT: A study was done to assess the average distances of root apices of mandibular first molar, second molar, and second premolar to inferior alveolar nerve canal (IANC), among males and females in central India. MATERIALS AND METHODS: High-resolution full-volume cone-beam computed tomography (CBCT) scans were obtained from the radiology database at the Sri Aurobindo College of Dentistry, Indore. After scrutinizing the database, CBCT of 40 males and 40 females that conformed to the inclusion and exclusion criteria were selected for the study. RESULTS: All the data were analyzed using SPSS, Version 16. Descriptive statistics of the variables and measurements are presented using Students t-test (paired and unpaired), and correlation between age was tabled by Karl Pearson's correlation coefficient method. CONCLUSION: For the second premolar, the average distance to the IANC was 0.88-13.03 mm for males and 0.00 5.49 mm for females. The average distance of IANC to the mesial root apex of first molar was 1.46-13.23 mm for males and 0.93-8.03 mm for females. For the second molar, the average distance was 1.31-14.71 mm for males and 0.00-6.91 mm for females (values on left side were shorter as compared to right side). In the overall population, only second molar exhibited significant difference in the distance from root apex to IANC when compared bilaterally. In addition to gender differences, age-related differences were found to be significant for the first molar on left side and second molar on the right side of the population (P< 0.05). PMID- 27411663 TI - The prevalence of malocclusion and orthodontic treatment needs in school going children of Nalagarh, Himachal Pradesh, India. AB - OBJECTIVE: The aim of this study was to determine the prevalence of malocclusion and orthodontic treatment need in 13-18-year-old schoolchildren of Nalagarh, Himachal Pradesh, India using the Index of Orthodontic Treatment need (IOTN) and to analyze the treatment needs between males and females and correlation between the esthetic component (AC) and dental health component (DHC) of IOTN. SUBJECTS AND METHODS: The sample comprised 2000 school children (1125 females and 875 males) who had not undergone orthodontic treatment. No radiographs, study casts, were used; IOTN was calculated from clinical examination. RESULTS: DHC results showed that little need for orthodontic treatment was found in 31.6% and moderate need in 30.85%. A great need was estimated at 37.55%. Severe contact point displacement of more than 4 mm was the most common occlusal feature in the definite treatment need group, followed by increased overjet, impeded eruption of teeth, and anterior or posterior cross bite. AC results showed that little need for orthodontic treatment was in 86.15%, moderate need in 8.90%, and great need in 4.95%. LIMITATIONS: Index does not consider midline discrepancy, soft tissue abnormalities, and AC does not include Class III and Class II div 2 malocclusion photographs. CONCLUSIONS: There seems a discrepancy in the proportion of children needing orthodontic treatment on esthetic and dental health grounds. This study provides baseline data on the need and demand for orthodontic treatment among the sample which is important for planning public orthodontic and dental services. PMID- 27411664 TI - Role of endothelin-1 in periodontal diseases: A structured review. AB - BACKGROUND AND OBJECTIVE: Endothelin-1 (ET-1) is a 21-amino acid peptide and is a potent vasoconstrictor produced by endothelial cells. It plays a role in the development of diseases such as hypertension and atherosclerosis. Previous studies have identified ET-1 in gingival tissues obtained from patients affected by chronic periodontitis or gingival overgrowth. Thus, there is a need to appraise the role of ET-1 in periodontal disease. MATERIALS AND METHODS: The electronic search strategy included the databases such as PubMed, PubMed Central, LILACS, MEDLINE, ScienceDirect, MeSH, Cochrane database of systematic reviews, and EMBASE databases. Hand search of relevant journals was also carried out until September 2013. The included studies were both cross-sectional and longitudinal performed in vivo/in vitro, which measures the expression of ET-1 from various cells of the periodontium and in periodontal disease. Further, studies assessing the factors which influence ET-1 expression were included in the study. RESULTS: A total of 15 articles were found relevant and fulfilled the inclusion criteria posed in this review. Ten studies discussed the concentration of ET-1 in periodontal disease, whereas eight studies investigated the cells expressing ET 1. Nine studies assessed the factors influencing ET-1 expression and two studies evaluated the influence of ET-1 on inflammatory mediators and other cytokines. The results suggested that ET-1 is elevated in periodontal diseases and is influenced by inflammatory cytokines and periodontal pathogens. CONCLUSION: ET-1 was found to have a role in periodontal disease, but further research will be required to substantiate its use as a biomarker. PMID- 27411665 TI - Intraoral plasmablastic non-hodgkin's lymphoma associated with human immunodeficiency virus. AB - Plasmablastic Lymphoma of oral cavity is an aggressive rare form of Non Hodgkin's Lymphoma which is an Acquired Immuno Deficiency Syndrome defining condition. Head and neck region is the second most common area for extranodal NHL's primarily involving gingiva and palate, which often presents as a diagnostic problem. We report a case of PBL in a 19 year old female patient later diagnosed as Human Immunodeficiency Virus (HIV) positive. She presented with expanding painful ulceroproliferative lesion involving left mandible and gingiva of 20 days duration. Histopathological examination and immunohistochemical analysis confirmed the diagnosis. Uncommon discovery of multiple bony lesions in whole body CT and hypercalcemia raise a question about Multiple Myeloma (MM). Literature showed very few cases with osteolytic lesions and none of the cases reported multiple bone lesions in skull. Our case report stresses the importance of differentiating this extremely rare case of PBL with skull lesions from MM. PMID- 27411666 TI - Sleep/awake status throughout the night and circadian motor activity patterns in older nursing-home residents with or without dementia, and older community dwelling people without dementia. AB - BACKGROUND: Sleep disturbances are commonly observed in older nursing home residents, mainly in combination with dementia. However, sleep-associated circadian motor activity patterns have not been thoroughly investigated in Japanese nursing homes. The present study aimed to respectively clarify the effect of community living and the presence of dementia on sleep disturbances and interrupted activity rhythm of older nursing-home residents with or without dementia and older community-dwelling people without dementia. METHODS: Actigraph devices worn on the participants' non-dominant wrists for seven days were used to collect objective measurements of the sleep/awake status throughout the night and the circadian motor activity patterns. The presence of dementia was assessed by a trained medical doctor using the residents' records and the Clinical Dementia Rating (CDR). The functional capacity of the participants was determined using the Barthel Index (BI). RESULTS: Fifty-one older people in Akita prefecture were included in the current study, consisting of 17 residents with dementia (mean age: 82.2 years), 17 residents without dementia (84.5 years), and 17 community dwelling people (83.6 years). The results showed that older nursing-home residents with dementia had significantly a lower rate of sleep efficiency and a longer awake time throughout the night than the other groups. Older nursing-home residents with and without dementia had more fragmented rhythm than community dwelling people without dementia. CONCLUSION: These results provide evidence of poor sleep/awake status throughout the night and interrupted circadian activity rhythms in nursing-home residents with and without dementia. However, further studies performed according to dementia classifications are needed. PMID- 27411668 TI - An autopsy case of a centenarian with the pathology of senile dementia of the neurofibrillary tangle type. AB - A Japanese woman showed slowly progressive memory disturbance since the age of 85 years. Later, disorientation gradually appeared. Head computed tomography revealed severe hippocampal atrophy, particularly in the posterior portion, and lateral ventricular dilatation, particularly in the inferior horn at the age of 99 years. The amygdala was relatively preserved from atrophy, and atrophy of the frontal lobe was relatively mild for her age. Apolipoprotein E gene analysis showed the epsilon3 homozygous phenotype. The woman died at the age of 101 years, and her clinical diagnosis was mild Alzheimer's disease. No apparent behavioural and psychological symptoms of dementia were observed during the disease course. Autopsy revealed severe hippocampal atrophy with numerous neurofibrillary tangles and ghost tangles, particularly in the hippocampal region, but senile plaques were rarely observed in the brain. The pathological findings were compatible with senile dementia of the neurofibrillary tangle type, whereas other neurodegenerative disorders were not recognized. The clinicopathologic findings of the present case are considered significant for the clinical diagnosis and pathogenesis of senile dementia of the neurofibrillary tangle type. PMID- 27411671 TI - Universality of the electrical transport in granular metals. AB - The universality of the ac electrical transport in granular metals has been scarcely studied and the actual mechanisms involved in the scaling laws are not well understood. Previous works have reported on the scaling of capacitance and dielectric loss at different temperatures in Co-ZrO2 granular metals. However, the characteristic frequency used to scale the conductivity spectra has not been discussed, yet. This report provides unambiguous evidence of the universal relaxation behavior of Pd-ZrO2 granular thin films over wide frequency (11 Hz-2 MHz) and temperature ranges (40-180 K) by means of Impedance Spectroscopy. The frequency dependence of the imaginary parts of both the impedance Z" and electrical modulus M" exhibit respective peaks at frequencies omegamax that follow a thermal activation law, omegamax ? exp(T(1/2)). Moreover, the real part of electrical conductivity sigma' follows the Jonscher's universal power law, while the onset of the conductivity dispersion also corresponds to omegamax. Interestingly enough, omegamax can be used as the scaling parameter for Z", M" and sigma', such that the corresponding spectra collapse onto single master curves. All in all, these facts show that the Time-Temperature Superposition Principle holds for the ac conductance of granular metals, in which both electron tunneling and capacitive paths among particles compete, exhibiting a well characterized universal behavior. PMID- 27411669 TI - A Reciprocal Effects Model of the Temporal Ordering of Coping and Defenses. AB - This study aimed to examine how coping and defenses are related over time, using a two-wave cross-lagged panel design. Coping and defenses were assessed before and after a sport competition in a sample of 296 competitive athletes. Partial least squares path modeling results showed that (a) pre-competitive mature defenses predicted increases in the use of task-oriented coping during competition; (b) pre-competitive immature defenses predicted an increase in the use of disengagement-oriented coping during competition; and (c) pre-competitive task-oriented coping predicted an increase in the use of immature defenses during competition. Overall, our findings suggest that defenses predict the use of coping and conversely, that coping predicts the use of defenses in psychological adjustment to stressful situations. These findings have important theoretical and practical implications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27411667 TI - Avidity characterization of genetically engineered T-cells with novel and established approaches. AB - BACKGROUND: Adoptive transfer of genetically engineered autologous T-cells is becoming a successful therapy for cancer. The avidity of the engineered T-cells is of crucial importance for therapy success. We have in the past cloned a T-cell receptor (TCR) that recognizes an HLA-A2 (MHC class I)-restricted peptide from the prostate and breast cancer- associated antigen TARP. Herein we perform a side by-side comparison of the TARP-specific TCR (TARP-TCR) with a newly cloned TCR specific for an HLA-A2-restricted peptide from the cytomegalovirus (CMV) pp65 antigen. RESULTS: Both CD8(+) T-cells and CD4(+) T-cells transduced with the HLA A2-restricted TARP-TCR could readily be detected by multimer analysis, indicating that the binding is rather strong, since binding occured also without the CD8 co receptor of HLA-A2. Not surprisingly, the TARP-TCR, which is directed against a self-antigen, had weaker binding to the HLA-A2/peptide complex than the CMV pp65 specific TCR (pp65-TCR), which is directed against a viral epitope. Higher peptide concentrations were needed to achieve efficient cytokine release and killing of target cells when the TARP-TCR was used. We further introduce the LigandTracer technology to study cell-cell interactions in real time by evaluating the interaction between TCR-engineered T-cells and peptide-pulsed cancer cells. We were able to successfully detect TCR-engineered T-cell binding kinetics to the target cells. We also used the xCELLigence technology to analyzed cell growth of target cells to assess the killing potency of the TCR-engineered T cells. T-cells transduced with the pp65 - TCR exhibited more pronounced cytotoxicity, being able to kill their targets at both lower effector to target ratios and lower peptide concentrations. CONCLUSION: The combination of binding assay with functional assays yields data suggesting that TARP-TCR-engineered T cells bind to their target, but need more antigen stimulation compared to the pp65-TCR to achieve full effector response. Nonetheless, we believe that the TARP TCR is an attractive candidate for immunotherapy development for prostate and/or breast cancer. PMID- 27411672 TI - Interaction of drought and ozone exposure on isoprene emission from extensively cultivated poplar. AB - The combined effects of ozone (O3 ) and drought on isoprene emission were studied for the first time. Young hybrid poplars (clone 546, Populus deltoides cv. 55/56 x P. deltoides cv. Imperial) were exposed to O3 (charcoal-filtered air, CF, and non-filtered air +40 ppb, E-O3 ) and soil water stress (well-watered, WW, and mild drought, MD, one-third irrigation) for 96 days. Consistent with light saturated photosynthesis (Asat ), intercellular CO2 concentration (Ci ) and chlorophyll content, isoprene emission depended on drought, O3 , leaf position and sampling time. Drought stimulated emission (+38.4%), and O3 decreased it ( 40.4%). Ozone increased the carbon cost per unit of isoprene emission. Ozone and drought effects were stronger in middle leaves (13th-15th from the apex) than in upper leaves (6th-8th). Only Asat showed a significant interaction between O3 and drought. When the responses were up-scaled to the entire-plant level, however, drought effects on total leaf area translated into around twice higher emission from WW plants in clean air than in E-O3 . Our results suggest that direct effects on plant emission rates and changes in total leaf area may affect isoprene emission from intensively cultivated hybrid poplar under combined MD and O3 exposure, with important feedbacks for air quality. PMID- 27411674 TI - Modulating epigenetic HAT activity for reinstating acetylation homeostasis: A promising therapeutic strategy for neurological disorders. AB - Epigenetic mechanisms are emerging as a fundamental regulatory switch in neuronal function. Acetylation homeostasis governed by the antagonistic activities of HATs and HDACs plays a critical role in neuronal gene activity. It is now becoming increasingly clear that several neurodevelopmental, neurodegenerative, and neuropsychiatric disorders are caused by aberrant changes in chromatin acetylation. Several HATs have been shown to be vital for neuronal processes such as synaptic plasticity and memory formation. Thus not surprisingly, dysregulation of such HATs has been implicated in the pathogenesis of several neurodegenerative diseases including Huntington's disease (HD) and Alzheimer's disease (AD). The current therapeutic strategy involves the use of small-molecule histone deacetylase inhibitors to compensate the acetylation deficits arising due to loss of HAT activity. Despite the promising therapeutic effects, the lack of isoform (target) specificity of HDACi raises concerns regarding their applicability. Mounting evidences about the role of HATs in neuronal survival, learning and memory has triggered a new wave of modulating specific HATs as a novel therapeutic option to tackle neurodegenerative diseases. In this review we focus on different HAT families and the critical roles they play in neural development and how the altered acetylation homeostasis culminates in neurodegeneration. Further, we describe the HDACi-based therapeutic approach and its flip side in overcoming neurodegenerative diseases. Furthermore, we discuss the therapeutic potential of HAT modulators in reinstating acetylation homeostasis to ameliorate neurodegenerative disorders. PMID- 27411673 TI - Immune suppressive properties of artemisinin family drugs. AB - Artemisinin and its derivatives are the first-line antimalarial drugs, and have saved millions of lives across the globe, especially in developing world. The discovery of artemisinin by Youyou Tu was awarded the 2015 Nobel Prize in Physiology or Medicine. In addition to treating malaria, accumulating evidences suggest that artemisinin and its derivatives also possess potent anti inflammatory and immunoregulatory properties. We recently showed that artesunate, an artemisinin analog, dramatically ameliorated autoimmune arthritis by selectively diminishing germinal center B cells. Herein, we review the immunosuppressive properties of artemisinin family drugs and the potential underlying mechanisms. PMID- 27411675 TI - Cortisol and CBG - Getting cortisol to the right place at the right time. AB - Cortisol is transported in the blood by corticosteroid-binding globulin (CBG), a non-inhibitory member of the serpin family of serine protease inhibitors. Recent structural advances reveal how CBG acts as a releasing-agent as well as a carrier of cortisol. Taken together, the structures of the various forms of CBG and of the closely related thyroxine binding-globulin, show how the inherent conformational mechanism of the serpins has been adapted to modulate hormone release to the tissues by changes in binding affinities. A deduction from this, of the temperature dependence of hormone binding, is remarkably borne out with CBG, with a doubling in plasma free cortisol as the body temperature rises to 39 degrees C. Another insight, against a dogma in the corticosteroid field, is that the proteolytic cleavage of CBG in inflammation results in a partial and not a complete loss of cortisol binding. This becomes of medical importance in conjunction with recent evidence of a pool of the circulating cleaved-form of CBG. It is now evident that tissue levels of free cortisol are buffered by two responsive plasma pools, intact CBG with a high binding-affinity and, particularly in inflammation and sepsis, a further pool of cleaved-CBG with a ten fold lower affinity. The new molecular understandings, as well as providing insights into the differential release of circulating hormones, also open prospects for therapeutic interventions and draw attention to the potential of CBG and TBG as vehicles for the targeted delivery of drugs. PMID- 27411676 TI - Elective laparoscopic cholecystectomy without intraoperative cholangiography: role of preoperative magnetic resonance cholangiopancreatography - a retrospective cohort study. AB - BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard treatment for gallbladder diseases. Intraoperative cholangiography (IOC) can reduce biliary complications of LC; however, with the emergence of magnetic resonance cholangiopancreatography (MRCP), IOC nowadays is faced with unprecedented challenge. The purpose of this study is to evaluate whether preoperative MRCP can safely replace IOC during elective LC in terms of retained common bile duct (CBD) stones and bile duct injury (BDI). METHODS: A retrospective study on candidates for elective LC who underwent IOC or preoperative MRCP between January 2009 and December 2014 was conducted. RESULTS: In the IOC group, 1972 patients underwent LC and 213 required IOC. In the MRCP group, 2268 patients underwent LC and 257 required MRCP. In the IOC group, the rate of retained CBD stones was 0.45 % without IOC and 1.41 % with IOC. In five of 157 patients who underwent IOC, endoscopic retrograde cholangiopancreatography or laparoscopic CBD exploration showed no evidence of CBD stones. In the MRCP group, the rate of retained CBD stones was 0.45 % without MRCP. No patients with normal MRCP findings returned with symptomatic CBD stones during 1-year follow-up. The rate of BDIs was 0.20 % in the IOC group and 0.13 % in the MRCP group. CONCLUSIONS: Selective use of preoperative MRCP is an effective and safe strategy when conducting elective LC to treat gallstones. LC resorting to preoperative MRCP can be performed safely without IOC, with an acceptable rate of retained CBD stones and BDIs. PMID- 27411677 TI - Low surgical complication rates in cochlear implantation for young children less than 1 year of age. AB - OBJECTIVE: To identify risk factors for perioperative morbidity among a large national cohort of pediatric patients undergoing cochlear implantation. STUDY DESIGN: Retrospective study utilizing the American College of Surgeons National Surgical Quality Improvement Program Pediatric database (2012-2013). METHODS: Pediatric cochlear implantation cases were identified using current procedural terminology 69930. Patients were categorized by age, and operative characteristics along with 30-day perioperative outcomes were analyzed. RESULTS: We identified 1,351 cases of pediatric cochlear implantation. The median age was 3.6 years, and 73 patients were less than 1 year of age. Of 21 complication occurrences (1.55%), superficial incisional surgical site infection (SSI) was the most common (n = 13, 61.9%). Thirty-nine patients (2.9%) required readmission. The median operative time was 142 minutes, and the mean postoperative length of stay was 0.58 days. When comparing patients younger than 1 year old to those 1 year or older, no significant differences were noted in complication rate, postoperative length of stay, or reoperation rate. Patients less than 1 year of age were more likely to be readmitted (6.9% vs. 2.7%, P = 0.04) and had longer mean operative times (191 minutes vs. 160 minutes, P = 0.0015). Steroid use was a risk factor for unplanned reoperation, SSI, and readmission. CONCLUSION: Despite a slight increase in readmission rates and operative times among patients less than 1 year of age, cochlear implantation appears to be safe in this population, with complication rates, reoperation rates, and postoperative lengths of stay similar to children undergoing the procedure at the current U.S. Food and Drug Administration-approved age of 1 year and older. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:720-724, 2017. PMID- 27411678 TI - Psychometric Properties of the HEXACO-100. AB - Psychometric properties of the 100-item English-language HEXACO Personality Inventory-Revised (HEXACO-PI-R) were examined using samples of online respondents ( N = 100,318 self-reports) and of undergraduate students ( N = 2,868 self- and observer reports). The results were as follows: First, the hierarchical structure of the HEXACO-100 was clearly supported in two principal components analyses: each of the six factors was defined by its constituent facets and each of the 25 facets was defined by its constituent items. Second, the HEXACO-100 factor scales showed fairly low intercorrelations, with only one pair of scales (Honesty Humility and Agreeableness) having an absolute correlation above .20 in self report data. Third, the factor and facet scales showed strong self/observer convergent correlations, which far exceeded the self/observer discriminant correlations. PMID- 27411679 TI - What Lies Beyond Neuroticism? An Examination of the Unique Contributions of Social-Cognitive Vulnerabilities to Internalizing Disorders. AB - Extensive research has identified various social-cognitive vulnerabilities for internalizing disorders. However, few studies have assessed multiple disorders simultaneously, so it is unclear whether these vulnerabilities are transdiagnostic or specific risk factors. Their unique associations with disorders are also uncertain, given that they correlate strongly with neuroticism and one other. Psychiatric outpatients completed self-report and interview measures of six disorders (depression, generalized anxiety disorder, posttraumatic stress disorder, social anxiety, panic, obsessive-compulsive disorder), and personality (the Big Five, neuroticism facets, and four vulnerabilities: anxiety sensitivity, intolerance of uncertainty, perfectionism, experiential avoidance). All constructs were modeled as latent variables using structural equation modeling. All four vulnerabilities were closely associated with neuroticism, loading on its anxiety facet in factor analyses. Furthermore, after accounting for the contribution of neuroticism facets, intolerance of uncertainty and experiential avoidance were not uniquely associated with any disorders, and perfectionism was only related to obsessive-compulsive disorder. However, anxiety sensitivity accounted for substantial unique variance in several disorders (i.e., depression, social anxiety, posttraumatic stress disorder, and panic). We discuss theoretical and clinical implications of these results. PMID- 27411680 TI - Root system-based limits to agricultural productivity and efficiency: the farming systems context. AB - BACKGROUND: There has been renewed global interest in both genetic and management strategies to improve root system function in order to improve agricultural productivity and minimize environmental damage. Improving root system capture of water and nutrients is an obvious strategy, yet few studies consider the important interactions between the genetic improvements proposed, and crop management at a system scale that will influence likely success. SCOPE: To exemplify these interactions, the contrasting cereal-based farming systems of Denmark and Australia were used, where the improved uptake of water and nitrogen from deeper soil layers has been proposed to improve productivity and environmental outcomes in both systems. The analysis showed that water and nitrogen availability, especially in deeper layers (>1 m), was significantly affected by the preceding crops and management, and likely to interact strongly with deeper rooting as a specific trait of interest. CONCLUSIONS: In the semi arid Australian environment, grain yield impacts from storage and uptake of water from depth (>1 m) could be influenced to a stronger degree by preceding crop choice (0.42 t ha-1), pre-crop fallow management (0.65 t ha-1) and sowing date (0.63 t ha-1) than by current genetic differences in rooting depth (0.36 t ha-1). Matching of deep-rooted genotypes to management provided the greatest improvements related to deep water capture. In the wetter environment of Denmark, reduced leaching of N was the focus. Here the amount of N moving below the root zone was also influenced by previous crop choice or cover crop management (effects up to 85 kg N ha-1) and wheat crop sowing date (up to 45 kg ha-1), effects which over-ride the effects of differences in rooting depth among genotypes. These examples highlight the need to understand the farming system context and important G * E * M interactions in studies on proposed genetic improvements to root systems for improved productivity or environmental outcomes. PMID- 27411681 TI - Fine-tuning of root elongation by ethylene: a tool to study dynamic structure function relationships between root architecture and nitrate absorption. AB - BACKGROUND: Recently developed genetic and pharmacological approaches have been used to explore [Formula: see text]/ethylene signalling interactions and how the modifications in root architecture by pharmacological modulation of ethylene biosynthesis affect nitrate uptake. KEY RESULTS: Structure-function studies combined with recent approaches to chemical genomics highlight the non specificity of commonly used inhibitors of ethylene biosynthesis such as AVG (l aminoethoxyvinylglycine). Indeed, AVG inhibits aminotransferases such as ACC synthase (ACS) and tryptophan aminotransferase (TAA) involved in ethylene and auxin biosynthesis but also some aminotransferases implied in nitrogen (N) metabolism. In this framework, it can be assumed that the products of nitrate assimilation and hormones may interact through a hub in carbon (C) and N metabolism to drive the root morphogenetic programme (RMP). Although ethylene/auxin interactions play a major role in cell division and elongation in root meristems, shaping of the root system depends also on energetic considerations. Based on this finding, the analysis is extended to nutrient ion hormone interactions assuming a fractal or constructal model for root development. CONCLUSION: Therefore, the tight control of root structure-function in the RMP may explain why over-expressing nitrate transporter genes to decouple structure-function relationships and improve nitrogen use efficiency (NUE) has been unsuccessful. PMID- 27411682 TI - Outbreak of foodborne gastroenteritis in a senior high school in South-eastern Ghana: a retrospective cohort study. AB - BACKGROUND: On 4th February 2015, a group of Senior High School students from Fanteakwa district presented to the emergency unit of the district hospital with complaints of abdominal pain, vomiting and diarrhoea. All the students had eaten from a specific food vendor and had neither eaten any other common meal that day nor the previous day. A foodborne disease outbreak was suspected. We investigated to verify the outbreak, determine its magnitude, identify the source and implement control measures. METHODS: A retrospective cohort study was conducted. We reviewed medical records and interviewed patrons of the food vendor. We collected data on age, sex, signs and symptoms, date of illness onset, date of admission, date of discharge, treatments given and outcome. A case of foodborne disease was any person in the school with abdominal pain, vomiting and or diarrhoea from 4th to 11th February 2015 and had eaten from the food vendor. We conducted active case search to identify more cases. We conducted environmental assessment and collected clinical and food samples for laboratory testing. Descriptive and inferential statistical analyses were performed using Stata 12.0. RESULTS: A total of 68 cases were recorded giving overall attack rate of 35.79 % (68/190) with no death. Of these, 51.47 % (35/68) were males. Mean age of case patients was 17.8 (standard deviation +/-1.62). The index case, a 17-year-old female student ate from the food vendor on 4th February at 9:00 am and fell ill at 3:40 pm later that day. Compared to those who ate other food items, students who drank water from container at the canteen were more likely to develop foodborne disease at statistically significant levels [RR = 2.6, 95 % CI = (2.11 3.15)]. Clostridium perfringens (C. perfringens) and Salmonella species (Salmonella spp) were isolated from water and stew respectively. Clinical features of case-patients were compatible with both organisms. CONCLUSION: A foodborne gastroenteritis outbreak occurred in a Senior High School in Fanteakwa District from 4th to 7th February 2015. The most probable aetiologic agent was C. perfringens with contaminated water at canteen as the vehicle of transmission. Concurrent Salmonella spp infection could not be ruled out. Rapid outbreak response helped in controlling the outbreak. PMID- 27411684 TI - Measles. AB - Measles is an infectious disease in humans caused by the measles virus (MeV). Before the introduction of an effective measles vaccine, virtually everyone experienced measles during childhood. Symptoms of measles include fever and maculopapular skin rash accompanied by cough, coryza and/or conjunctivitis. MeV causes immunosuppression, and severe sequelae of measles include pneumonia, gastroenteritis, blindness, measles inclusion body encephalitis and subacute sclerosing panencephalitis. Case confirmation depends on clinical presentation and results of laboratory tests, including the detection of anti-MeV IgM antibodies and/or viral RNA. All current measles vaccines contain a live attenuated strain of MeV, and great progress has been made to increase global vaccination coverage to drive down the incidence of measles. However, endemic transmission continues in many parts of the world. Measles remains a considerable cause of childhood mortality worldwide, with estimates that >100,000 fatal cases occur each year. Case fatality ratio estimates vary from <0.01% in industrialized countries to >5% in developing countries. All six WHO regions have set goals to eliminate endemic transmission of MeV by achieving and maintaining high levels of vaccination coverage accompanied by a sensitive surveillance system. Because of the availability of a highly effective and relatively inexpensive vaccine, the monotypic nature of the virus and the lack of an animal reservoir, measles is considered a candidate for eradication. PMID- 27411686 TI - Altererythrobacter confluentis sp. nov., isolated from water of an estuary environment. AB - A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated KEM-4T, was isolated from water of an estuary environment on the Yellow Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain KEM-4T grew optimally at pH 7.0-8.0, at 30 degrees C and in the presence of 1.0-2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain KEM-4T fell within the clade comprising the type strains of species of the genus Altererythrobacter, clustering with the type strains of Altererythrobacter aestiaquae, Altererythrobacter gangjinensis and Altererythrobacter luteolus, showing 95.0-96.5 % sequence similarity. Sequences similarities to the type strains of the other species of the genus Altererythrobacter were 93.1-95.1 %. Strain KEM-4T contained Q-10 as the predominant ubiquinone and C18 : 1omega7c, summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and C17 : 1omega6c as the major fatty acids. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid. The DNA G+C content of strain KEM-4T was 59.5 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness, revealed that strain KEM-4T is separated from species of the genus Altererythrobacter with validly published names. On the basis of the data presented, strain KEM-4T is considered to represent a novel species of the genus Altererythrobacter, for which the name Altererythrobacter confluentissp. nov. is proposed. The type strain is KEM-4T (=KCTC 52259T=NBRC 112305T). PMID- 27411683 TI - Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab(r) Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma. AB - BACKGROUND: This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab ((r))-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). METHODS: Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m(2) on day 1; 2) IV nab paclitaxel 140 mg/m(2) on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m(2) on day 1. Treatment continued for 4-6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. RESULTS: Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6-12 months). Grade >= 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. CONCLUSIONS: Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. TRIAL REGISTRATIONS: ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012. PMID- 27411685 TI - [Treatment of dermatoses : Significance and use of glucocorticoids in fixed combination with antifungals]. AB - Treating eczema with fungal and/or bacterial superinfections or superficial mycoses are a common problem in daily practice. A fungal superinfection as a consequence of a diminished skin barrier might complicate the course of eczema. In addition, in an inflammatory superficial mycotic infection a delayed-type hypersensitivity reaction may result in healing of the lesion, but might also be responsible for irreversible damage of epidermal structures. An example is permanent hair loss by scarring alopecia in the context of inflammatory tinea capitis. In both cases, combination of an antifungal and a glucocorticoid is appropriate in therapy, preferentially in topical application. The use of azole antimycotics is especially helpful, as they are also effective against gram positive bacteria. PMID- 27411687 TI - p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice. AB - Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120. Tumors that developed in the triple-knockout mice were mostly basal sarcomatoid carcinomas that displayed overt nuclear atypia and multinucleation. In line with the strong reduction in ILC incidence in triple-knockout mice compared to E-cadherin and p53 double knockout mice, no functional redundancy of p120 family members was observed in mouse ILC development, as expression and localization of ARVCF, p0071 or delta catenin was unaltered in ILCs from triple-knockout mice. In conclusion, we show that loss of p120 in the context of the p53-deficient mouse models is dominant over E-cadherin inactivation and its inactivation promotes the development of basal, epithelial-to-mesenchymal-transition (EMT)-type invasive mammary tumors. PMID- 27411689 TI - Syndecans in heart fibrosis. AB - Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing the contents of the current review on syndecans in cardiac fibrosis. The heart is subjected to various forms of pathological stimuli, e.g., myocardial infarction, hypertension, valvular stenosis, infection, or an inherited genetic mutation, triggering responses in cells resident in the heart. Here, we focus on the responses of cardiac fibroblasts directing changes in the extracellular matrix resulting in cardiac fibrosis. A family of four transmembrane proteoglycans, syndecan-1 to -4, is expressed in the cell membrane of cardiac fibroblasts and is generally up regulated in response to the above-mentioned pathological stimuli. Syndecans carry glycosaminoglycan chains on their extracellular domain, binding a plethora of molecules involved in fibrosis, e.g., growth factors, cytokines, immune cell adhesion proteins, and pathogens. Syndecans have a short cytoplasmic tail involved in pro-fibrotic signaling. The signaling and cellular processes governed by syndecans in the heart in response to pathological stimuli regulate important aspects of extracellular matrix remodeling and fibrosis and have mainly been studied in cardiac remodeling in response to cardiac infarction and pressure overload. In general, adequate timing and the quantity and quality of fibrosis are absolutely crucial for heart function and survival, determining cardiac stiffness, contractility, compliance, probability of rupture, dilation, and diastolic and systolic function. Syndecan-1 and -4 have mainly been studied in the heart and are discussed in this review (LV left ventricle). PMID- 27411688 TI - Epigenetic mechanisms of cell adhesion-mediated drug resistance in multiple myeloma. AB - Multiple myeloma cells acquire the resistance to anti-cancer drugs through physical and functional interactions with the bone marrow microenvironment via two overlapping mechanisms. First, bone marrow stromal cells (BMSCs) produce soluble factors, such as interleukin-6 and insulin-like growth factor-1, to activate signal transduction pathways leading to drug resistance (soluble factor mediated drug resistance). Second, BMSCs up-regulate the expression of cell cycle inhibitors, anti-apoptotic members of the Bcl-2 family and ABC drug transporters in myeloma cells upon direct adhesion [cell adhesion-mediated drug resistance (CAM-DR)]. Elucidation of the mechanisms underlying drug resistance may greatly contribute to the advancement of cancer therapies. Recent investigations, including ours, have revealed the involvement of epigenetic alterations in drug resistance especially CAM-DR. For example, we found that class I histone deacetylases (HDACs) determine the sensitivity of proteasome inhibitors and the histone methyltransferase EZH2 regulates the transcription of anti-apoptotic genes during the acquisition of CAM-DR by myeloma cells. In addition, another histone methyltransferase MMSET was shown to confer drug resistance to myeloma cells by facilitating DNA repair. These findings provide a rationale for the inclusion of epigenetic drugs, such as HDAC inhibitors and histone methylation modifiers, in combination chemotherapy for MM patients to increase the therapeutic index. PMID- 27411690 TI - Regulation of glucose transport by thyroid hormone in rat ovary. AB - Thyroid hormone (TH) plays an important role in regulating ovarian development. However, the mechanism involved remains unclear. Evidence suggests that glucose is essential for ovarian development, and its uptake is mediated by several glucose transporter proteins (Glut). We have investigated the effects of TH on Glut in rat ovary. Immature rats were treated with 6-propyl-2-thiouracil or L thyroxine to induce hypothyroidism (hypo) or hyperthyroidism (hyper), respectively. Ovarian weights significantly decreased in both treated groups compared with the control group, although the body weights were not markedly altered. Glut1 expression significantly decreased without further changes being detected in the other Glut isforms in the hypo group and was accompanied by minimal change in mRNA content. The expression of Glut1 decreased in the hyper group. In contrast, L-thyroxine significantly increased Glut4 mRNA level and protein content but had little effect on Glut2 and Glut3 expression. Serum glucose concentrations in the hyper group were dramatically reduced compared with those in the control group. However, the serum glucose levels in the hypo group were not significantly changed. In addition, equine chorionic gonadotropin (eCG) increased ovarian weights in both the hypo and hyper groups compared with those in the rats without eCG injection. Glut2-4 protein content was significantly increased by eCG in hyper rats. Only the Glut4 mRNA content was significantly increased by eCG in the hyper group. Although the mRNA levels were not significantly changed by eCG in the hypo group, the protein level of Glut4 was markedly up-regulated. Serum glucose levels were not significantly altered by eCG in the two groups. Thus, dysfunction of the thyroid gland changes Glut expression in rat ovary and ovarian growth, both of which are also regulated by gonadotropin. PMID- 27411692 TI - New perspectives on role of tumor microenvironment in progression of cutaneous squamous cell carcinoma. AB - Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing worldwide. Solar UV radiation is an important risk factor for cSCC and leads to genetic and epigenetic changes both in epidermal keratinocytes and dermal cells. Tumor cells in cutaneous cSCCs typically harbor several driver gene mutations, but epidermal keratinocytes in sun-exposed normal skin also contain mutations in these same genes. Therefore, alterations in the microenvironment of premalignant lesions are evidently required for their progression to invasive and metastatic cSCC. For example, alterations in the composition of basement membrane and dermal extracellular matrix are early events in cSCC progression. The presence of microbial structures and the influx of inflammatory cells promote the secretion of proteases, which in turn regulate the availability of growth factors, cytokines, and chemokines and thus influence the growth and invasion of cSCC. Together, these observations emphasize the role of the tumor microenvironment in the progression of cSCC and identify it as a novel therapeutic target in cSCC and other malignant tumors. Graphical abstract Tumor-stroma interactions in the progression of cutaneous squamous cell carcinoma (cSCC). Epidermal layer is separated by a well-organized basement membrane (BM) from the dermal layer. UV radiation, other environmental insults, and aging target both epidermal keratinocytes and dermal fibroblasts and lead to genetic and epigenetic changes in these cells. In addition, epidermal keratinocytes in normal sun-exposed skin harbor several mutations in the cSCC driver genes. During transition to premalignant actinic keratosis (AK), the differentiation of keratinocytes is disturbed resulting in a neoplastic epithelium with hyperplastic cells. Expression of proteinases, such as matrix metalloproteinases (MMP) by neoplastic cells and activated stromal fibroblasts and macrophages is induced in AK, and collagen XV and XVIII are lost from the dermal BM. Furthermore, inflammatory cells accumulate at the site of the hyperplastic epithelium. During a later stage of cSCC progression, the number of inflammatory cells increases, and the expression of complement components and inhibitors by tumor cells is induced (CFI complement factor I, CFH complement factor H, FHL-1 Factor H-like protein 1). In addition to MMPs, activated fibroblasts also produce growth factors and promote inflammation, growth, and invasion of tumor cells. PMID- 27411691 TI - The process of mammalian mitochondrial protein synthesis. AB - Oxidative phosphorylation (OXPHOS) is the mechanism whereby ATP, the major energy source for the cell, is produced by harnessing cellular respiration in the mitochondrion. This is facilitated by five multi-subunit complexes housed within the inner mitochondrial membrane. These complexes, with the exception of complex II, are of a dual genetic origin, requiring expression from nuclear and mitochondrial genes. Mitochondrially encoded mRNA is translated on the mitochondrial ribosome (mitoribosome) and the recent release of the near atomic resolution structure of the mammalian mitoribosome has highlighted its peculiar features. However, whereas some aspects of mitochondrial translation are understood, much is to be learnt about the presentation of mitochondrial mRNA to the mitoribosome, the biogenesis of the machinery, the exact role of the membrane, the constitution of the translocon/insertion machinery and the regulation of translation in the mitochondrion. This review addresses our current knowledge of mammalian mitochondrial gene expression, highlights key questions and indicates how defects in this process can result in profound mitochondrial disease. PMID- 27411693 TI - Evolutionary plasticity of acipenseriform genomes. AB - Acipenseriformes is an order of ray-finned fishes, comprising 27 extant species of sturgeons and paddlefishes inhabiting waters of the Northern Hemisphere. The order has a basal position within Actinopteri (ray-finned fish minus polypterids) and is characterized by many specific morphological and genomic features, including high diploid chromosome numbers, various levels of ploidy between species, unclear sex determination, and propensity to interspecific hybridization. Recent advances in molecular genetics, genomics, and comparative cytogenetics produced novel data on different aspects of acipenseriform biology, including improved phylogenetic reconstructions and better understanding of genome structure. Here, we discuss the cytogenetic and genomic traits of acipenseriforms and their connection with polyploidization and tolerance to interspecific hybridization. PMID- 27411694 TI - Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. AB - INTRODUCTION: Multiple sclerosis (MS) is more common in women and can occur during childbearing years; thus, information on outcomes following exposure to MS therapy during pregnancy is important. No formal studies of daclizumab have been conducted in pregnant women. Here, we report available nonclinical and clinical data on pregnancy outcomes from the daclizumab clinical study program. METHODS: Reproductive and developmental toxicity studies were conducted in cynomolgus monkeys. Reports of pregnancies that occurred during the daclizumab clinical study program through March 9, 2015 were collated and summarized. In the event of pregnancy, daclizumab was discontinued and safety monitoring continued. RESULTS: Studies in cynomolgus monkeys showed no daclizumab-related effects on maternal well-being, embryo-fetal development, indirect fertility end points, and pre- and postnatal development and growth. Across the clinical study program, 38 pregnancies were reported in 36 daclizumab-exposed women (on treatment <=6 months from last dose); 20 resulted in live births and four (11%) in spontaneous abortions or miscarriages. One congenital heart defect (complex transposition of great vessels) occurred in one live birth (considered unrelated to daclizumab); daclizumab had been discontinued and intramuscular interferon beta-1a and lisinopril were used at conception. Eight women had an elective termination, two had an ectopic pregnancy, and two were lost to follow-up; two pregnancy outcomes are pending. Six additional pregnancies occurred in five women >6 months after their last daclizumab dose; in one additional pregnancy, exposure was unknown. CONCLUSION: Spontaneous abortion rate in daclizumab-exposed women was consistent with early pregnancy loss in the general population (12%-26%). Data on pregnancies exposed to daclizumab do not suggest an increased risk of adverse fetal or maternal outcomes, although the numbers are too small for definitive conclusions. CLINICALTRIALS. GOV IDENTIFIERS: NCT00390221, NCT01064401, NCT01462318, NCT00870740, NCT01051349, and NCT01797965. FUNDING: Biogen and AbbVie Biotherapeutics Inc. PMID- 27411695 TI - Oncogenic Marek's disease herpesvirus encodes an isoform of the conserved regulatory immediate early protein ICP27 generated by alternative promoter usage. AB - Herpesvirus gene expression is temporally regulated, with immediate early (IE), early (E) and late (L) genes. ICP27, which is involved in post-transcriptional regulation, is the only IE gene product conserved in all herpesviruses. We show here that the ICP27 transcript of the oncogenic Marek's disease virus shares the same polyadenylation signal as the bicistronic glycoprotein K-ICP27 transcript and is regulated by alternative promoter usage, with transcription from its own promoter (pICP27) or that of gK (pgK). The pgK can generate a spliced ICP27 transcript yielding an N-terminal-deleted ICP27 isoform (ICP27DeltaN) that, like ICP27, co-localizes with the SR protein in infected cells, but with a diffuse nuclear distribution. The pICP27 includes functional responsive elements (REs) for SP1, AP1 and CREB, is essentially active during the lytic phase and leads to exclusive expression of the native form of ICP27. The alternative promoter, pgK, including active REs for GATA, P53 and CREB, preferentially generates the gK transcript during the lytic phase and the spliced ICP27 transcript (ICP27DeltaN) during the latent phase. An analysis of the DNA methylation marks of each promoter showed that pgK was systematically demethylated, whereas pICP27 was methylated during latency and demethylated during the lytic stage. Thus, MDV ICP27 gene expression is dependent on alternative promoters, the usage of which is regulated by DNA methylation, which differs between viral stages. PMID- 27411696 TI - [Necrotizing funisitis : Histopathological indicator of occult congenital syphilis]. AB - Congenital syphilis is a rare disease in central Europe. Placental changes may be non-specific but a typical finding is necrotizing funisitis of the umbilical cord. In a case report we describe how the histopathological incidental finding of B lymphocyte-rich, necrotizing funisitis led to the diagnosis of a previously unknown Treponema pallidum infection in parents and their newborn child. The pathological suspicion of congenital syphilis, although rare, has implications for the clinical management (serological evaluation of parents and child as well as the social environment, evaluation of viral coinfection and treatment decision) and is a notifiable disease. PMID- 27411698 TI - Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control. AB - OBJECTIVE: Lipohypertrophy (LHT) is common in insulin-treated patients but its exact impact on insulin absorption and action is unclear. RESEARCH DESIGN AND METHODS: In this crossover study, 13 patients with type 1 diabetes received subcutaneous abdominal injections of 0.15 units/kg insulin lispro into LHT (confirmed by examination and ultrasound) and normal adipose tissue (NAT). On one day, a euglycemic clamp was performed with two injections each into LHT and NAT, and on another day one injection per region was given before a standardized mixed meal (75 g carbohydrates), all in randomized order. RESULTS: Compared with NAT, LHT reduced insulin absorption (mean area under the insulin concentration curve [AUCINS0-4h] 131 vs. 165 h * mU/L [LHT vs. NAT]; Cmax 61 vs. 79 mU/L, P < 0.02, respectively) and effect (areas under glucose infusion rate [GIR] curves [AUCGIR0 4h 625 vs. 775 mg/kg, P < 0.05]) but increased intrasubject variability ([coefficient of variation] AUCINS0-4h 52 vs. 11%, Cmax 55 vs. 15%, AUCGIR0-4h 57 vs. 23%, all P < 0.01). Postprandial blood glucose (BG) concentrations were >=26% higher with LHT (AUCBG0-5h 731 vs. 513 mg * h/dL, BGmax 199 vs. 157 mg/dL, 2-h BG 150 vs. 104 mg/dL, 5-h BG 145 vs. 81 mg/dL, all P < 0.05) and maximum concentrations occurred later. Hypoglycemia (BG <=50 mg/dL) occurred numerically less frequently with LHT injection (two vs. six patients), whereas profound hyperglycemia (BG >=300 mg/dL) only occurred with LHT injection (two patients). Tmax-INS did not differ between LHT and NAT in either study. CONCLUSIONS: Insulin absorption and action are blunted and considerably more variable with LHT injection, leading to profound deterioration in postprandial glucose control. PMID- 27411697 TI - Changes in Mortality in People With IGT Before and After the Onset of Diabetes During the 23-Year Follow-up of the Da Qing Diabetes Prevention Study. AB - OBJECTIVE: People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS: We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS: During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2-12.0) before and 19.4/1,000 person-years (95% CI 11.9-23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1-42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6-35.0%) in those who progressed to type 2 diabetes in 10-20 years, and 13.9% (95% CI 7.0 20.3%) in those who did not develop to type 2 diabetes within 20 years. Time dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18-2.52]). CONCLUSIONS: As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes. PMID- 27411700 TI - Dentate nucleus connectivity in adult patients with multiple sclerosis: functional changes at rest and correlation with clinical features. AB - BACKGROUND AND OBJECTIVE: The dentate nucleus, which is the largest of the cerebellar nuclei, plays a critical role in movement and cognition. The aim of our study was to assess any changes in dentate functional connectivity (FC) in adult relapsing remitting multiple sclerosis (RR-MS) patients and to investigate possible clinical correlates. MATERIALS AND METHODS: In all, 54 patients and 24 healthy subjects (HS) underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), three-dimensional-T1-weighted and resting state (RS) functional images; they also underwent a cognitive evaluation, that is, attention and information processing speed, by means of the Paced Auditory Serial Addition Test (PASAT). Patients were also scored according to Expanded Disability Status Scale (EDSS). RS-MRI data were analysed using FMRIB Software Library (FSL) tools, with the seed-based method to identify dentate FC. RESULTS: When compared with HS, patients exhibited brain atrophy and widespread DTI abnormalities, as well as greater FC between the dentate nucleus and cortical areas, particularly in the frontal and parietal lobes. Within these areas, FC in patients correlated inversely with clinical impairment. Finally, FC correlated inversely with lesion load and microstructural brain damage. CONCLUSION: Our findings indicate that dentate FC at rest is altered in MS patients. Whether these functional changes are induced by the disease and play a compensatory role remains to be established. PMID- 27411699 TI - Mortality in Type 1 Diabetes in the DCCT/EDIC Versus the General Population. AB - OBJECTIVE: Historically, mortality in type 1 diabetes has exceeded that in the general population. We compared mortality in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study cohort to that of the current general U.S. RESEARCH DESIGN AND METHODS: The DCCT (1983-1993) compared intensive versus conventional therapy, with HbA1c levels of ~7 vs. 9%, respectively, over an average of 6.5 years of treatment. EDIC is the observational follow-up study of the DCCT (1994 to the present). Vital status was ascertained for 97.5% of the original DCCT cohort (n = 1,441) after a mean of 27 years follow-up. Expected mortality during DCCT/EDIC was estimated using the current age-, sex-, and race-specific risks in the general U.S. population, and the observed versus expected mortality compared using standardized mortality ratios (SMRs) and Poisson regression models. RESULTS: Mortality in the DCCT intensive therapy group was nonsignificantly lower than that in the general U.S. population (SMR = 0.88 [95% CI 0.67, 1.16]), whereas mortality in the DCCT conventional therapy group was significantly greater than that in the general population (SMR = 1.31 [95% CI 1.05, 1.65]). The SMR increased with increasing mean HbA1c, and above an HbA1c of 9%, the rate of increase in SMR among females was greater than that among males. CONCLUSIONS: Overall mortality in the combined DCCT/EDIC cohort was similar to that of the general population but was higher in the DCCT conventional therapy group. Mortality increased significantly with increasing mean HbA1c, more so among females than males, especially for HbA1c >9%. PMID- 27411702 TI - Propensity methods for multiple sclerosis: The devil is in the details. PMID- 27411703 TI - A potential mechanism underlying the effects of acupuncture on insulin resistance. PMID- 27411701 TI - Defining brain volume cutoffs to identify clinically relevant atrophy in RRMS. AB - OBJECTIVE: To define values of normalized brain volume (NBV) that can be categorized as low, medium, or high, according to baseline characteristics of relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: Expected NBV (eNBV) was calculated for each patient based on age, disease duration, sex, baseline Expanded Disability Status Scale (EDSS), and T2-lesion volume, entering these variables into a multiple regression model run on 2342 RRMS patients (pooled FREEDOMS/FREEDOMS-II population). According to the difference between their observed NBV and their eNBV, patients were classified as having low NBV, medium NBV, or high NBV. We evaluated whether these NBV categories were clinically meaningful by assessing correlation with disability worsening. RESULTS: The distribution of differences between observed NBV and eNBV was used to categorize patients as having low NBV, medium NBV or high NBV. Taking the high NBV group as reference, the hazard ratios (HRs) for 2-year disability worsening, adjusted for treatment effect, were 1.23 (95% confidence interval (CI): 0.92 1.63, p = 0.16) for the medium NBV and 1.75 (95% CI: 1.26-2.44, p = 0.001) for the low NBV. The predictive value of NBV groups was preserved over 4 years. Treatment effect appeared more evident in low-NBV patients (HR = 0.58) than in medium-NBV (HR = 0.72) and in high-NBV (HR = 0.80) patients; however, the difference was not significant ( p = 0.57). CONCLUSION: RRMS patients can be categorized into disability risk groups based on individual eNBV values according to baseline demographics and clinical characteristics. PMID- 27411704 TI - The neurological and cognitive consequences of hyperthermia. AB - An elevated temperature has many aetiologies, both infective and non-infective, and while the fever of sepsis probably confers benefit, there is increasing evidence that the central nervous system is particularly vulnerable to damage from hyperthermia. A single episode of hyperthermia may cause short-term neurological and cognitive dysfunction, which may be prolonged or become permanent. The cerebellum is particularly intolerant to the effects of heat. Hyperthermia in the presence of acute brain injury worsens outcome. The thermotoxicity involved occurs via cellular, local, and systemic mechanisms. This article reviews both the cognitive and neurological consequences and examines the mechanisms of cerebral damage caused by high temperature. PMID- 27411705 TI - A review of new challenges and prospects for malaria elimination in Mutare and Mutasa Districts, Zimbabwe. AB - This review outlines and discusses the new challenges in malaria control and prospects for its elimination in Mutare and Mutasa Districts, Zimbabwe. The burden of malaria has declined significantly over the past 5 years in most regions in Zimbabwe, including Mutare and Mutasa Districts. The nationwide malaria reduction has been primarily linked to scaled-up vector control interventions and early diagnosis and treatment with effective anti-malarial medicines. The successes recorded have prompted Zimbabwe's National Malaria Control Programme to commit to a global health agenda of eliminating malaria in all districts in the country. However, despite the decline in malaria burden in Mutare and Mutasa Districts, there is clear evidence of new challenges, including changes in vector behaviour, resistance to insecticides and anti-malarial medicines, invasion of new areas by vectors, vectors in various combination of sympatry, changes in vector proportions, outdoor malaria transmission, climate change and lack of meticulousness of spray operators. These new challenges are likely to retard the shift from malaria control to elimination in Mutare and Mutasa Districts. PMID- 27411706 TI - Erratum to: 3D Printed Modeling of the Mitral Valve for Catheter-Based Structural Interventions. PMID- 27411708 TI - Changes in Small Intestine Tissue Compressed by a Linear Stapler Based on Cole Y Model. AB - Clarifying changes in gastrointestinal tissue compressed by surgical stapler is a crucial prerequisite for stapler design optimization. For this study, a stapler was modified, and multifrequency bioimpedance of a porcine small intestine tissue compressed by the stapler was measured. The Cole Y model was fitted to the bioimpedance, and changes in tissue were analyzed using model parameters: G 0, extracellular fluid conductance; DeltaG, intracellular fluid conductance; C cpeF, equivalent capacitance of cell membrane. The changes could be divided into two stages: first, all parameters decreased sharply with slopes more than 15.70 +/- 2.67, 4.25 +/- 1.23 MUS/s and 72.68 +/- 6.99 pF/s respectively; and subsequently, with an increase in compression strength, G 0 decreased with slopes less than 2.54 +/- 0.40 MUS/s, DeltaG decreased slightly with slope of 0.26 +/- 0.04 MUS/s after fluctuating mildly, and C cpeF remained nearly invariant after initially increasing with slope of -2.94 +/- 0.64 pF/s. In conclusion, when the stapler is closed, a portion of tissue is squeezed out of the measurement space, causing all parameters' sharp decrease. Subsequently, the stapler continues compressing the tissue, leading to extracellular fluid expulsion. The changes in intracellular fluid are related to the compression strength and may be explained by cell restoration. This study could provide a basis for stapler design optimization. PMID- 27411707 TI - Simvastatin Treatment Modulates Mechanically-Induced Injury and Inflammation in Respiratory Epithelial Cells. AB - Mechanical forces in the respiratory system, including surface tension forces during airway reopening and high transmural pressures, can result in epithelial cell injury, barrier disruption and inflammation. In this study, we investigated if a clinically relevant pharmaceutical agent, Simvastatin, could mitigate mechanically induced injury and inflammation in respiratory epithelia. Pulmonary alveolar epithelial cells (A549) were exposed to either cyclic airway reopening forces or oscillatory transmural pressure in vitro and treated with a wide range of Simvastatin concentrations. Simvastatin induced reversible depolymerization of the actin cytoskeleton and a statistically significant reduction the cell's elastic modulus. However, Simvastatin treatment did not result in an appreciable change in the cell's viscoelastic properties. Simvastatin treated cells did exhibit a reduced height-to-width aspect ratio and these changes in cell morphology resulted in a significant decrease in epithelial cell injury during airway reopening. Interestingly, although very high concentrations (25-50 uM) of Simvastatin resulted in dramatically less IL-6 and IL-8 pro-inflammatory cytokine secretion, 2.5 uM Simvastatin did not reduce the total amount of pro-inflammatory cytokines secreted during mechanical stimulation. These results indicate that although Simvastatin treatment may be useful in reducing cell injury during airway reopening, elevated local concentrations of Simvastatin might be needed to reduce mechanically-induced injury and inflammation in respiratory epithelia. PMID- 27411709 TI - Sonomicrometry-Based Analysis of Post-Myocardial Infarction Regional Mechanics. AB - Following myocardial infarction (MI), detrimental changes to the geometry, composition, and mechanical properties of the left ventricle (LV) are initiated in a process generally termed adverse post-MI remodeling. Cumulatively, these changes lead to a loss of LV function and are deterministic factors in the progression to heart failure. Proposed therapeutic strategies to target aberrant LV mechanics post-MI have shown potential to stabilize LV functional indices throughout the remodeling process. The in vivo quantification of LV mechanics, particularly within the MI region, is therefore essential to the continued development and evaluation of strategies to interrupt the post-MI remodeling process. The present study utilizes a porcine MI model and in vivo sonomicrometry to characterize MI region stiffness at 14 days post-MI. Obtained results demonstrate a significant dependence of mechanical properties on location and direction within the MI region, as well as cardiac phase. While approaches for comprehensive characterization of LV mechanics post-MI still need to be improved and standardized, our findings provide insight into the issues and complexities that must be considered within the MI region itself. PMID- 27411711 TI - Stem Cell Guardians - Old and New Perspectives in LSC Biology. AB - The introduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (CML) has revolutionised disease outcome. However, despite this, progression to blast phase disease is high in those that do not achieve complete cytogenetic and major molecular response on standard therapy. As well as BCR-ABL-dependent mechanisms, disease persistence has been shown to play a key role. Disease persistence suggests that, despite a targeted therapeutic approach, BCR-ABL-independent mechanisms are being exploited to sustain the survival of a small population of cells termed leukaemic stem cells (LSCs). Increasing evidence highlights the importance of self-renewal and survival pathways in this process. This review will focus on the role of stem-cell restricted self-renewal pathways, namely Hedgehog, Notch, and Bone Morphogenic Pathway (BMP). Wingless-Int/beta-Catenin (Wnt/beta-Catenin) signalling will be discussed within a further review in this series in view of its regulatory role in GSK3beta. Further to this, we will highlight the role of key transcriptional regulators, namely p53 and c- MYC, in targeting wider deregulated networks. PMID- 27411710 TI - Continuous plasma perfusion of dual cartridges in series: rationale and early clinical experience. AB - To improve the efficiency of plasma perfusion on eliminating plasma paraquat (PQ), we designed continuous plasma perfusion of dual cartridges in series (CPPDCS) on Diapact Braun CRRT machine. The goals of this study were to evaluate the effective of CPPDCS on paraquat removal in patients with acute paraquat intoxication. Our results show that the PQ clearance rate of dual cartridges was significantly higher than that of single cartridge at 1st, 2nd, 3rd, and 4th plasma perfusion. Compared with single-cartridge plasma perfusion, CPPDCS significantly reduced the frequency of cartridge replacement, shorten the time of perfusion. These results indicate that CPPDCS is effective than plasma perfusion of single cartridge on PQ clearance rate and may provide an effective treatment for PQ poisoning. PMID- 27411712 TI - Hematoma Expansion: Clinical and Molecular Predictors and Corresponding Pharmacological Treatment. AB - BACKGROUND: Hematoma expansion is a detrimental event of intracerebral hemorrhage (ICH) which results in progressive neurologic deteriorations and poor outcomes. OBJECTIVE: To summariz the current understanding of the mechanisms underlying hematoma expansion and discuss the potential approaches of treatment and prevention. RESULTS: Although the exact mechanism of hematoma expansion is unclear, accumulating evidences suggest that multiple clinical markers such as coagulation/hemostasis dysfunction, higher blood pressure and BRAIN scores, higher serum glucose and/or glycosylated hemoglobin A1c, serum creatinine, Factor XIII and international normalized ratio (INR), lower serum cholesterol or LDL cholesterol, and fibrinogen, may be correlated with incidents of hematoma expansion. Furthermore, activation of several molecular pathways (i.e. plasma kallikrein, von Willebrand factor, N-methyl-Daspartate and its receptor, cytokines/ adipokines, cellular fibronectin and apolipoprotein Eepsilon2 allele) may lead to hematoma expansion. CONCLUSION: Prospective study for hematoma expansion How to predict the patients Who are at highest risk of hematoma expansion is more challengeable than restricting hematoma expansion itself following acute ICH. Seeking and detecting risk markers in plasma that can be intervened appropriately is meaningful for patients with potential hematoma expansion, which may contribute to improve clinical outcomes in patients suffering from ICH. PMID- 27411713 TI - Transcriptome analysis of woodland strawberry (Fragaria vesca) response to the infection by Strawberry vein banding virus (SVBV). AB - BACKGROUND: Woodland strawberry (Fragaria vesca) infected with Strawberry vein banding virus (SVBV) exhibits chlorotic symptoms along the leaf veins. However, little is known about the molecular mechanism of strawberry disease caused by SVBV. METHODS: We performed the next-generation sequencing (RNA-Seq) study to identify gene expression changes induced by SVBV in woodland strawberry using mock-inoculated plants as a control. RESULTS: Using RNA-Seq, we have identified 36,850 unigenes, of which 517 were differentially expressed in the virus-infected plants (DEGs). The unigenes were annotated and classified with Gene Ontology (GO), Clusters of Orthologous Group (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The KEGG pathway analysis of these genes suggested that strawberry disease caused by SVBV may affect multiple processes including pigment metabolism, photosynthesis and plant-pathogen interactions. CONCLUSIONS: Our research provides comprehensive transcriptome information regarding SVBV infection in strawberry. PMID- 27411714 TI - Driving fatalities on US presidential election days: a reanalysis. AB - BACKGROUND: Redelmeier and Tibshirani reported a statistical analysis in the Journal of the American Medical Association in 2008 indicating that presidential election days are strongly associated (P < 0.001) with an increased risk of driving fatalities (as measured by the number of persons involved in fatal crashes). FINDINGS: We present evidence indicating that the risk of driving fatalities on presidential election days is neither statistically nor substantively unusual. Although we find weakly suggestive evidence that presidential elections may increase the risk of driving fatalities during election hours, any increase appears to be entirely offset by a lowered risk during non-election hours. CONCLUSIONS: We find weaker support for an association between election days and driving fatalities than was previously reported. Our results suggest caution in evaluating policy prescriptions that presuppose that election days pose an unusual risk to the public. PMID- 27411715 TI - Transcriptomic analysis reveals abnormal muscle repair and remodeling in survivors of critical illness with sustained weakness. AB - ICU acquired weakness (ICUAW) is a common complication of critical illness characterized by structural and functional impairment of skeletal muscle. The resulting physical impairment may persist for years after ICU discharge, with few patients regaining functional independence. Elucidating molecular mechanisms underscoring sustained ICUAW is crucial to understanding outcomes linked to different morbidity trajectories as well as for the development of novel therapies. Quadriceps muscle biopsies and functional measures of muscle strength and mass were obtained at 7 days and 6 months post-ICU discharge from a cohort of ICUAW patients. Unsupervised co-expression network analysis of transcriptomic profiles identified discrete modules of co-expressed genes associated with the degree of muscle weakness and atrophy in early and sustained ICUAW. Modules were enriched for genes involved in skeletal muscle regeneration and extracellular matrix deposition. Collagen deposition in persistent ICUAW was confirmed by histochemical stain. Modules were further validated in an independent cohort of critically ill patients with sepsis-induced multi-organ failure and a porcine model of ICUAW, demonstrating disease-associated conservation across species and peripheral muscle type. Our findings provide a pathomolecular basis for sustained ICUAW, implicating aberrant expression of distinct skeletal muscle structural and regenerative genes in early and persistent ICUAW. PMID- 27411716 TI - Risk factors for antenatal hypovitaminosis D in an urban district in Malaysia. AB - BACKGROUND: Pregnant women form one of the high risk groups facing hypovitaminosis D. Low level of vitamin D will affect directly or indirectly both mother and fetus. Screening vitamin D in the first trimester of pregnancy is important to determine the necessary preventive action. Therefore, this study was aimed to determine the prevalence of hypovitaminosis D and its risk factors among pregnant women in the first trimester. METHODS: A cross sectional study was carried out among first trimester pregnant women during their first antenatal visit. Samples were taken from different ethnicities in an urban district in Malaysia. A total of 396 respondents (99 % response rate) aged 18-40 years completed self-administered and guided questionnaire (characteristics and risk factors), validated semi-quantitative food frequency questionnaire for vitamin D in Malaysia (FFQ vitamin D/My), anthropometric measures (weight and height), blood test for serum 25(OH)D, skin measurement using Mexameter (MX 18) and Fitzpatrick Skin Type Chart Measurement (FSTCM). Data were analyzed to determine the association between risk factors and hypovitaminosis D. RESULTS: The prevalence of hypovitaminosis D (serum 25(OH)D < 50 nmol/L) was 90.4 % (358). The mean age of respondents was 28.06 +/- 4.09 years old. The independent predictors of hypovitaminosis D were Malay ethnicity (OR 33.68; 95 % CI: 12.81, 88.56), Indian ethnicity (OR 16.86; 95 % CI: 3.78,75.20), secondary education (OR 12.12; 95 % CI: 2.71, 54.16) and tertiary education (OR 14.38; 95 % Cl: 3.31, 62.45). CONCLUSION: Awareness should be raised among Malay and Indian pregnant women with secondary and tertiary education who consumed vitamin D (especially milk) poorly in order to prevent adverse health outcomes. Further studies need to be conducted among health care workers to determine their level of knowledge related to vitamin D, as they are front liner in detecting the hypovitaminosis D. PMID- 27411718 TI - No HIV transmission from condomless sex when partner is on ART, study shows. PMID- 27411719 TI - Chondroprotective and anti-inflammatory effects of ChondroT, a new complex herbal medication. AB - BACKGROUND: Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. METHODS: ChondroT was validated using a convenient and accurate high-performance liquid chromatography-photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti inflammatory effects of ChondroT were studied by Western blotting of pro inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. RESULTS: ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1beta-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-kB and production of inflammatory mediators, such as IL-1beta, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. CONCLUSIONS: These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis. PMID- 27411720 TI - The Health of Women and Children After Surviving Intimate Partner Violence. AB - Few studies have explored the perspectives of survivors of intimate partner violence (IPV) regarding their health and their children's health, their experiences accessing and utilizing health care, and health initiatives that would best serve their families' needs. We facilitated focus groups with female IPV survivors and adolescents who witnessed IPV. Women described their health and their children's health as poor and reported challenges with health care utilization, whereas teenagers generally perceived their health as typical for their age. Participants requested health education workshops, community resources, and social support. This study lays the foundation for further research and the development of health initiatives. PMID- 27411717 TI - Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. AB - To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of alpha2 adrenergic and opioid receptors. These studies showed that alpha2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor-induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to alpha2 adrenergic signaling, a pathway known to be antinociceptive in humans. PMID- 27411722 TI - How to grow a kidney: patient-specific kidney organoids come of age. AB - The notion of regrowing a patient's kidney in a dish has fascinated researchers for decades and has spurred visions of revolutionary clinical applications. Recently, this option has come closer to reality. Key technologies have been developed to generate patient-specific pluripotent stem cells and to edit their genome. Several laboratories have devised protocols to differentiate patient specific pluripotent stem cells into kidney cells or into in vitro organoids that resemble the kidney with respect to cell types, tissue architecture and disease pathology. This was possible because of rapidly expanding knowledge regarding the cellular and molecular basis of embryonic kidney development. Generating kidney cells or organoids from patient-specific stem cells may prove to be clinically useful in several ways. First, patient-specific kidney cells or organoids could be used to predict an individual's response to stressors, toxins or medications and thereby develop personalized treatment decisions. Second, patient-specific stem cells harbour the individual's genetic defects. This may potentially enable genetic rescue attempts to establish the significance of a genetic defect in a stem cell-derived organoid or it may allow testing of patient-specific targeted therapies for kidney disease in vitro. From a tissue engineering perspective, patient-specific kidney organoids might provide a key advance towards engineering immunocompatible transplantable kidneys. This review article summarizes recent developments in the field and discusses its current limitations and future perspectives. PMID- 27411721 TI - Evaluation of C18 monolithic columns for radiochemical purity measurement. AB - Speeding the analysis of reaction aliquots, high-performance liquid chromatography (HPLC) fractions and final products continue to be an area of great interest in the study of radiopharmaceuticals. Translating recently developed rapid HPLC and ultra high-performance liquid chromatography analysis approaches to radio-HPLC can sometimes be fraught with peril, owing to specific peculiarities of online radiochemical chromatographic detection (notably, a proportionally large system volume for the radio-HPLC detector). In this study, we investigate an alternate approach for rapid radio-HPLC analysis where a 150-cm C18 monolithic column is used with a 15-min run time. To ascertain this method's ability to distinguish between radiolabeled compounds with acceptable (>=97%) and unacceptable purity, the results were compared with results from a conventional HPLC 45-min method using a 25-cm C18 column, where a large radiodetector cell volume is of lower impact. Overall, for the 54 radiolabeled compounds assayed by the two methods, there were similar measured radiochemical purities, but cases were also found where there were significantly large differences between the results (>1%). A calculated confidence of ~85% was found for the 15-min monolithic method's ability to accurately reproduce the corresponding result from the 25-cm column method. PMID- 27411723 TI - Pro: Higher serum bicarbonate in dialysis patients is protective. AB - Chronic metabolic acidosis is common in dialysis patients. Bicarbonate administration via the dialysate helps maintain the acid-base balance in these patients. Serum bicarbonate level in dialysis patients is determined by several factors that include dietary protein intake, nutritional status and dialysis prescription, etc. Additionally, a meaningful interpretation of serum bicarbonate in dialysis patients requires an understanding of complexities involving its measurement. Both very low as well very high levels of serum bicarbonate have been associated with adverse outcomes in observational studies. However, recent observational data, when adjusted for the confounding effects of nutritional status, do not associate higher predialysis serum bicarbonate with adverse consequences. At this time, there are no prospective studies available that have examined the association of serum bicarbonate with hard outcomes in dialysis patients. The ideal level of serum bicarbonate in dialysis patients is therefore unknown. This article examines the available data with regard to the benefits of higher predialysis serum bicarbonate. PMID- 27411724 TI - Con: Higher serum bicarbonate in dialysis patients is protective. AB - Metabolic acidosis is often observed in advanced chronic kidney disease, with deleterious consequences on the nutritional status, bone and mineral status, inflammation and mortality. Through clearance of the daily acid load and a net gain in alkaline buffers, dialysis therapy is aimed at correcting metabolic acidosis. A normal bicarbonate serum concentration is the recommended target in dialysis patients. However, several studies have shown that a mild degree of metabolic acidosis in patients treated with dialysis is associated with better nutritional status, higher protein intake and improved survival. Conversely, a high bicarbonate serum concentration is associated with poor nutritional status and lower survival. It is likely that mild acidosis results from a dietary acid load linked to animal protein intake. In contrast, a high bicarbonate concentration in patients treated with dialysis could result mainly from an insufficient dietary acid load, i.e. low protein intake. Therefore, a high pre dialysis serum bicarbonate concentration should prompt nephrologists to carry out nutritional investigations to detect insufficient dietary protein intake. In any case, a high bicarbonate concentration should be neither a goal of dialysis therapy nor an index of adequate dialysis, whereas mild acidosis could be considered as an indicator of appropriate protein intake. PMID- 27411725 TI - Moderator's view: Higher serum bicarbonate in dialysis patients is protective. AB - Several observational studies have reported an association between higher serum bicarbonate level and high mortality risk in dialysis patients. However, in such studies mere discovery of associations does not allow one to infer causal relationships. This association may be related to inadequate dietary protein intake that may lead to less acid generation and hence a higher serum bicarbonate level. Since undernutrition is a strong predictor of death in hemodialysis patients, the observed association may be an epiphenomenon and not a biologically plausible relationship. Higher protein and fluid intake between two subsequent hemodialysis treatments may lead to lower serum bicarbonate level. This low bicarbonate level may appear protective, as patients with higher food intake and better appetite generally exhibit greater survival. In the contemporary three stream proportioning system of hemodialysis treatment, the bicarbonate concentrate is separate from the acid concentrate, and the contribution of the acid concentrate organic acid (acetate, citrate or diacetate) to the delivered bicarbonate pool of the patient is negligible. The concept of 'total buffer' that assumes that the combination of bicarbonate and acetate concentrations in the dialysate are added equally as bicarbonate equivalents is likely wrong and based on the misleading notion that the acetate of the acid concentrate is fully metabolized to bicarbonate in the dialysate. Given these uncertainties it is prudent to avoid excessively high or low bicarbonate levels in dialysis patients. PMID- 27411726 TI - Short relaxation times but long transient times in both simple and complex reaction networks. AB - When relaxation towards an equilibrium or steady state is exponential at large times, one usually considers that the associated relaxation time tau, i.e. the inverse of the decay rate, is the longest characteristic time in the system. However, that need not be true, other times such as the lifetime of an infinitesimal perturbation can be much longer. In the present work, we demonstrate that this paradoxical property can arise even in quite simple systems such as a linear chain of reactions obeying mass action (MA) kinetics. By mathematical analysis of simple reaction networks, we pin-point the reason why the standard relaxation time does not provide relevant information on the potentially long transient times of typical infinitesimal perturbations. Overall, we consider four characteristic times and study their behaviour in both simple linear chains and in more complex reaction networks taken from the publicly available database 'Biomodels'. In all these systems, whether involving MA rates, Michaelis-Menten reversible kinetics, or phenomenological laws for reaction rates, we find that the characteristic times corresponding to lifetimes of tracers and of concentration perturbations can be significantly longer than tau. PMID- 27411727 TI - Mechanical modelling of tooth wear. AB - Different diets wear teeth in different ways and generate distinguishable wear and microwear patterns that have long been the basis of palaeodiet reconstructions. Little experimental research has been performed to study them together. Here, we show that an artificial mechanical masticator, a chewing machine, occluding real horse teeth in continuous simulated chewing (of 100 000 chewing cycles) is capable of replicating microscopic wear features and gross wear on teeth that resemble wear in specimens collected from nature. Simulating pure attrition (chewing without food) and four plant material diets of different abrasives content (at n = 5 tooth pairs per group), we detected differences in microscopic wear features by stereomicroscopy of the chewing surface in the number and quality of pits and scratches that were not always as expected. Using computed tomography scanning in one tooth per diet, absolute wear was quantified as the mean height change after the simulated chewing. Absolute wear increased with diet abrasiveness, originating from phytoliths and grit. In combination, our findings highlight that differences in actual dental tissue loss can occur at similar microwear patterns, cautioning against a direct transformation of microwear results into predictions about diet or tooth wear rate. PMID- 27411728 TI - What does it take to set goals for self-management in primary care? A qualitative study. AB - BACKGROUND: There is an increasing number of patients with a chronic illness demanding primary care services. This demands for effective self-management support, including collaborative goal setting. Despite the fact that primary care professionals seem to have difficulties implementing goal setting, little information is available about the factors influencing the complexity of this process in primary care. OBJECTIVE: The aim of this study was to contribute to an understanding of the complexity of self-management goal setting in primary care by exploring experts' and primary care professionals' experiences with self management goal setting and viewpoints regarding influencing factors. METHODS: A descriptive qualitative research methodology was adopted. Two focus groups and three individual interviews were conducted (total participants n = 17). Thematic content analysis was used to analyse the data. RESULTS: The findings were categorized into four main themes with subordinated subthemes. The themes focus around the complexity of setting non-medical goals and around professionals' skills and attitudes to negotiate and decide about goals with patients. Furthermore, patients' skills and attitudes for goal setting and the integration of goal setting in the time available were formulated as themes. CONCLUSIONS: Setting self-management goals in primary care, especially in family medicine, might require a shift from a medical perspective to a biopsychosocial perspective, with an increasing role set aside for the professional to coach the patient in expressing his self-management goals and to take responsibility for these goals. PMID- 27411729 TI - 'Parallel universes'? The interface between GPs and dentists in primary care: a qualitative study. AB - BACKGROUND: Patient care by GPs and dentists is organizationally separated in many health systems. Studies on how dentists and GPs cooperate and interact in daily care are scarce. OBJECTIVE: We aimed to explore the experiences of GPs and dentists as well their views and opinions regarding the inter-professional interface. METHODS: Qualitative semi-structured interviews were conducted with GPs (n = 8) and dentists (n = 8). The pre-developed interview guideline included questions concerning participant's experiences with the other specialty, important interdisciplinary medical issues and diseases and potential for improvement of cooperation. Interviews were transcribed verbatim and analyzed with qualitative content analysis. RESULTS: GPs and dentists perceived knowledge deficits in members of the other specialty and frequently criticized aspects of each other's patient management. Cooperation worked better if based on local networks of personally known colleagues. Participants reported many medical situations and diseases of common concern, most frequently diabetes and oral anticoagulation. There seemed to be considerable uncertainty about the management of anticoagulant therapy in patients undergoing invasive dental procedures in members of both specialties, despite existing guidelines. The separation of medical and dental university education and the lack of joint training were suggested by interviewees as reasons for the lack of interdisciplinary thinking. CONCLUSION: Except in cases of personal contact, interaction between GPs and dentists is often limited and sometimes difficult-despite numerous inter professional issues. Interdisciplinary approaches in continuing education, medical and dental school teaching and guideline development are potentially promising for promoting cooperation. PMID- 27411730 TI - 16-Membered Macrolide Lactone Derivatives Bearing a Triazole-Functionalized Arm at the Aglycone C13 Position as Antibacterial and Anticancer Agents. AB - A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ~2-4 MUg mL(-1) ; 2.55 5.09 MUm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ~1.35 3.70 MUm] potencies were those with the best aqueous solubility and bearing a saccharide-triazole arm at the C13 position of the aglycone. These derivatives preferentially bind at the ribosomal tunnel and show the most attractive selectivity indexes [SI; calculated relative to the human dermal fibroblast (HDF) cell line], even higher than that of the reference compound cytarabine. Results of molecular docking studies of this type of macrolide antibiotics at the ribosomal tunnel, together with experimentally determined lipophilicity and aqueous solubility values, as well as biological assay data revealed the importance of the introduced functional group at the aglycone C13 arm to the future design of anticancer and antibacterial drug candidates. Our results clearly indicate that the high antibacterial and anticancer activities of these types of macrolides do not necessarily depend on the presence of the aldehyde group at the aglycone lactone ring. PMID- 27411731 TI - Clinical experiences with microwave thermal ablation of lung malignancies. AB - Approximately 30% of early stage lung cancer patients are not surgical candidates due to medical co-morbidities, poor cardiopulmonary function and advanced age. These patients are traditionally offered chemotherapy and radiation, which have shown relatively modest improvements in mortality. For over a decade, percutaneous image-guided ablation has emerged as a safe, cost-effective, minimally invasive treatment alternative for patients who would otherwise not qualify for surgery. Although radiofrequency ablation (RFA) is currently the most extensively studied and widely utilised technique in the treatment of lung malignancies, there is a growing body of evidence that microwave ablation (MWA) has several unique benefits over RFA and cryoablation in the lung. This article reviews our institution's clinical experiences in the treatment of lung malignancies with MWA including patient selection, procedural technique, imaging follow-up, treatment outcomes and comparison of ablation techniques. PMID- 27411732 TI - Association between migraine and risk of venous thromboembolism: A nationwide cohort study. AB - BACKGROUND: -The link between arterial thromboembolism and migraine is well documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. METHODS: -We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. RESULTS: -During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92-1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40-4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration. PMID- 27411734 TI - Sunlight-assisted, biocatalytic formate synthesis from CO2 and water using silicon-based photoelectrochemical cells. AB - We report on a silicon-based photoelectrochemical cell that integrates a formate dehydrogenase from Thiobacillus sp. (TsFDH) to convert CO2 to formate using water as an electron donor under visible light irradiation and an applied bias. Our current study suggests that the deliberate integration of biocatalysis to a light harvesting platform could provide an opportunity to synthesize valuable chemicals with the use of earth-abundant materials and sustainable resources. PMID- 27411733 TI - Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs. AB - Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 MUM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3 hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4 methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 MUM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability. PMID- 27411735 TI - Development of REACH Generic Exposure Scenarios for Substances Used as Coformulants in Plant Protection Products. AB - This article reviews the interactions between the REACH (Registration, Evaluation, Authorization and restriction of Chemicals) regulation and the plant protection product regulation for substances used as coformulants in the European Union, and describes generic exposure scenarios developed for their exposure and risk assessment. The REACH exposure scenarios describe the operational conditions and risk management measures used in the risk assessment of a coformulant, and as such these translate as the boundaries of safe use. The generic exposure scenarios are designed to be simple, and closely integrate with REACH use descriptors and customized exposure models. Clustering of application methods and exposure determinants resulted in four generic exposure scenarios, each covering professional workers or consumers, and application of products in liquid, granular form, or applied on seeds. When used in conjunction with appropriate exposure models, the generic exposure scenarios support efficient first-tier risk assessment of coformulants by utilizing a higher level of abstraction and conservatism than typically used in plant protection product assessments. PMID- 27411736 TI - Room temperature phosphorescence from a guest molecule confined in the restrictive space of an organic-inorganic supramolecular assembly. AB - Stable room-temperature phosphorescence of guest aromatic molecules was achieved by the effective suppression of oxygen quenching. The organic capsule (first wall) suppressed static oxygen quenching by enclosing a guest molecule, and dynamic quenching via the capsule opening-closing process was well suppressed and manipulated by the intercalation of this capsule into the restrictive space between clay nanosheets (second wall). PMID- 27411737 TI - Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F Fluorodeoxyglucose PET/CT Study. AB - Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI) induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI. PMID- 27411738 TI - Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory. AB - Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID- 27411740 TI - Selective local lysis and sampling of live cells for nucleic acid analysis using a microfluidic probe. AB - Heterogeneity is inherent to biology, thus it is imperative to realize methods capable of obtaining spatially-resolved genomic and transcriptomic profiles of heterogeneous biological samples. Here, we present a new method for local lysis of live adherent cells for nucleic acid analyses. This method addresses bottlenecks in current approaches, such as dilution of analytes, one-sample-one test, and incompatibility to adherent cells. We make use of a scanning probe technology - a microfluidic probe - and implement hierarchical hydrodynamic flow confinement (hHFC) to localize multiple biochemicals on a biological substrate in a non-contact, non-destructive manner. hHFC enables rapid recovery of nucleic acids by coupling cell lysis and lysate collection. We locally lysed ~300 cells with chemical systems adapted for DNA or RNA and obtained lysates of ~70 cells/MUL for DNA analysis and ~15 cells/MUL for mRNA analysis. The lysates were introduced into PCR-based workflows for genomic and transcriptomic analysis. This strategy further enabled selective local lysis of subpopulations in a co-culture of MCF7 and MDA-MB-231 cells, validated by characteristic E-cadherin gene expression in individually extracted cell types. The developed strategy can be applied to study cell-cell, cell-matrix interactions locally, with implications in understanding growth, progression and drug response of a tumor. PMID- 27411739 TI - Transregional movement of multidrug-resistant tuberculosis in north China: an underlying threat to tuberculosis control. AB - Due to unbalanced distribution of health care resource in China, tuberculosis patients, especially multidrug-resistant tuberculosis (MDR-TB), prefer to suffer transregional movement for seeking better health care service in the first-tier cities. Here, we performed a study on the current status of transregional movement of tuberculosis in northern China by reviewing the medical record of TB patients hospitalized in Beijing Chest Hospital from 2011 to 2015. From 2011 to 2015, the proportion of non-Beijing in-patients had increased from 55.0% (996/1810) to 67.2% (1860/2769). In addition, we found that the rate of re treated among non-Beijing group was significantly higher than that among Beijing group. Compared with the proportion of pulmonary TB patients from non-Beijing, there were more extra-pulmonary TB patients from non-Beijing. In addition, 10.5% (164/1568) of Beijing in-patients and 26.5% (491/1858) of non-Beijing in-patients had MDR tuberculosis, and statistical analysis revealed that there was significantly higher proportion of MDR cases among non-Beijing group than Beijing group. In conclusion, our data demonstrate that an increasing proportion of TB patients from northern China seek health care in Beijing. In view of higher prevalence of MDR-TB cases among these patients, the transregional movement of MDR-TB will lead to ongoing MDR TB transmission in the community. PMID- 27411741 TI - Identification of a residue responsible for UDP-sugar donor selectivity of a dihydroxybenzoic acid glycosyltransferase from Arabidopsis natural accessions. AB - UDP-glycosyltransferase (UGT) plays a major role in the diversity and reactivity of plant specialized metabolites by catalyzing the transfer of the sugar moiety from activated UDP-sugars to various acceptors. Arabidopsis UGT89A2 was previously identified from a genome-wide association study as a key factor that affects the differential accumulation of dihydroxybenzoic acid (DHBA) glycosides in distinct Arabidopsis natural accessions, including Col-0 and C24. The in vitro enzyme assays indicate that these distinct metabolic phenotypes reflect the divergence of UGT89A2 enzyme properties in the Col-0 and C24 accessions. UGT89A2 from Col-0 is highly selective toward UDP-xylose as the sugar donor, and the isoform from C24 can utilize both UDP-glucose and UDP-xylose but with a higher affinity to the glucose donor. The sequences of the two isozymes only differ at six amino acid residues. Examination of these amino acid residues in more natural accessions revealed a strong correlation between the amino acid polymorphism at position 153 and the DHBA glycoside accumulation pattern. Site-directed mutagenesis that swapped residue 153 between UGT89A2 from Col-0 and C24 reversed the UDP-sugar preferences, indicating that residue 153 plays an important role in determining sugar donor specificity of UGT89A2. This study provides insight into the key amino acid changes that confer sugar donor selectivity on UGTs, and demonstrates the usefulness of natural variation in understanding the structure function relationship of enzymes involved in specialized metabolism. PMID- 27411742 TI - The role of the substrate structure in the on-surface synthesis of organometallic and covalent oligophenylene chains. AB - The influences of the substrate structure on the formation of one-dimensional organometallic and covalent oligomers on a Cu(110) surface were studied using scanning tunneling microscopy (STM), X-ray photoemission spectroscopy (XPS), and low energy electron diffraction (LEED) in ultrahigh vacuum (UHV). Vapor deposition of submonolayer 4,4''-dibromo-meta-terphenyl (DMTP) onto a Cu(110) surface at 300 K leads to scission of C-Br bonds and the formation of organometallic chains (cis/trans and all-trans) connected by C-Cu-C bonds. Larger islands (120 * 120 nm(2)) of all-trans zigzag organometallic chains as sole products were obtained by the deposition of DMTP onto Cu(110) held at 383 K. The domains are oriented along two directions with an angle of +/-13 degrees relative to the [0 0 1] direction due to the two-fold symmetry of the Cu(110) surface lattice. This study reveals at a sub-molecular level that the organometallic chains firstly lose copper atoms and then undergo C-C coupling into oligophenylene chains at a substrate temperature around 417 K. Annealing the large islands of organometallic chains at 458 K results in the formation of completely C-C covalently bonded zigzag oligophenylene chains. The zigzag angle of 125 degrees slightly deviates from the ideal value of 120 degrees . This is attributed to a stretching of the zigzag oligophenylene chains due to substrate template effects. PMID- 27411744 TI - Digital detection of T790M-yes or no to an ultrasensitive assay. PMID- 27411743 TI - Impact of Fluorine Substituents on pi-Conjugated Polymer Main-Chain Conformations, Packing, and Electronic Couplings. AB - Taking the pi-conjugated polymers PBDT[2X]T (X = H, F) as model systems, the effects of fluorine substitution on main-chain conformations, packing, and electronic couplings are examined. This combination of molecular dynamics simulations and solid-state NMR shows that a higher propensity for backbone planarity in PBDT[2F]T leads to more pronounced, yet staggered, chain stacking, which generally leads to higher electronic couplings and binding energy between neighboring chains. PMID- 27411745 TI - Understanding parenting concerns in cancer survivors with minor and young-adult children. AB - OBJECTIVE: Parents with cancer are concerned about the impact of their disease on their children. However, parenting concerns and associated factors in cancer survivors have not previously been analyzed. The purpose of this study is to examine parenting concerns and to test a path model for understanding parenting concerns in cancer survivors. METHODS: In a cross-sectional study, a total of 1416 parents with cancer (mean age 47.5years, 74% women) having minor or young adult children were recruited through two cancer registries. Parenting concerns were assessed using the Parenting Concerns Questionnaire. Structural equation modeling (SEM) was used to analyze the associations between social support, parenting confidence, emotional distress, family functioning and parenting concerns. RESULTS: Mothers reported higher total parenting concerns than fathers (p<0.001). We observed strong effects of emotional distress and parenting confidence on parenting concerns. Family dysfunctioning was associated with lower concerns. An indirect association between social support and parenting concerns was identified. CONCLUSION: Parenting concerns in cancer survivors display the need for interventions and after care programs that focus on affected families with minor and young adult children. The results of the structural path model illustrate the associations between psychological and interactional factors. Supporting parents with cancer in their parenting confidence and strengthen social support and family functioning may not only reduce the long-term burden on the parents themselves but also the burden on the entire family. PMID- 27411746 TI - Are MEDLINE searches sufficient for systematic reviews and meta-analyses of the diagnostic accuracy of depression screening tools? A review of meta-analyses. AB - OBJECTIVE: Database searches for studies of diagnostic test accuracy are notoriously difficult to filter, highly resource-intensive, and a potential barrier to quality evidence synthesis. We examined published meta-analyses of depression screening tool accuracy to evaluate the (1) proportion of included primary studies found in any online database in the original meta-analyses that were indexed in MEDLINE; (2) the proportion of patients from MEDLINE-indexed studies; and (3) the proportion of depression cases from studies indexed in MEDLINE. METHODS: MEDLINE and PsycINFO were searched from January 1, 2005 through October 31, 2014 for meta-analyses in any language on the accuracy of depression screening tools. RESULTS: We identified 16 eligible meta-analyses that included 398 primary study citations, which had been identified via an online database in the original meta-analyses, including 257 unique citations and 234 unique patient samples. The 234 unique patient samples included 69,957 total patients and 11,867 depression cases. Of these, 220 samples (94%) were from studies indexed in MEDLINE, including 97% of all patients and 96% of all depression cases. When applying a peer-reviewed search strategy in MEDLINE, 91% of all samples, 96% of patients and 95% of depression cases were retrieved. Results were similar for total and unique citations. CONCLUSIONS: Restricting searches to MEDLINE may capture almost all eligible studies, patients and depression cases. Although not examined in the present study, MEDLINE may not be indexed as quickly as other databases. Thus, MEDLINE searches should be complemented by date-limited searches of other databases for recent citations. PMID- 27411747 TI - A longitudinal study on anxiety, depressive and adjustment disorder, suicide ideation and symptoms of emotional distress in patients with cancer undergoing radiotherapy. AB - BACKGROUND: The aim of this study is to evaluate the presence of anxiety, depressive and adjustment disorders, suicide ideation, and symptoms of anxiety and depression in patients with cancer before (T1), and after radiotherapy (T2) and at the 1-month follow-up (T3). METHODS: A longitudinal study on 103 patients with cancer treated as outpatients undergoing radiotherapy was carried out, evaluating them three times (T1-T2-T3) according to DSM-IV criteria with the Mini International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale. RESULTS: Prevalence of the depressive disorders was: T1=6.8%, T2=3.9% and T3=3.9%; for anxiety disorders: T1=16.5%, T2=18.4% and T3=16.5%; for adjustment disorder: 10.7%, 5.8% and 7.8%; and for suicide ideation: T1=11.7%, T2=7.8% and T3=7.8%. In all, the presence of disorders was: T1=35%, T2=26.2%0.4% and T3=29.1%. At least one mental disorder was diagnosed in 46.6% of patients in one of the three times of the study. In relation to the symptoms, the prevalence of the possible cases of clinical anxiety was: T1=35.9%, T2=18.4% and T3=22.3%; the prevalence of possible cases of clinical depression was 19.4%, 16.5% and 10.7%, respectively; and the prevalence of emotional distress was 27.2%, 17.5% and 18.4%, respectively. All symptoms decreased significantly from T1 to T2 and from T1 to T3, with moderate effect sizes. No changes were observed between the end of the radiotherapy and the follow-up period. CONCLUSIONS: High prevalence of mental disorders and symptoms of anxiety, depression and distress were observed in the patients with cancer before finishing radiotherapy treatment and during the follow-up. FUNDING: Basurto University Hospital and Basque Foundation for Innovation and Research in Health-BIOEF. PMID- 27411748 TI - The stigma perceived by people bereaved by suicide and other sudden deaths: A cross-sectional UK study of 3432 bereaved adults. AB - OBJECTIVE: To test the hypothesis that perceived stigma scores in young adults bereaved by suicide are significantly higher than in young adults bereaved by other sudden deaths, whether blood-related to the deceased or not. METHODS: We conducted a cross-sectional study of all staff and students aged 18-40 at 37 UK higher educational institutions in 2010, and identified 3432 respondents who had experienced a sudden bereavement of a close contact since reaching the age of 10, either due to sudden natural causes, sudden unnatural causes, or suicide. We used multivariable regression to compare scores on the stigma, shame, responsibility and guilt subscales of the Grief Experience Questionnaire, adjusting for socio demographic factors and pre-bereavement psychopathology. RESULTS: People bereaved by suicide (n=614) had higher stigma scores than people bereaved by sudden natural death (n=2106; adjusted coefficient=2.52; 95% CI=2.13-2.90; p=<0.001) and people bereaved by sudden unnatural death (n=712; adjusted coefficient=1.69; 95% CI=1.25-2.13; p=<0.001). Shame, responsibility and guilt scores were also significantly higher in people bereaved by suicide, whether compared with bereavement by sudden natural death or sudden unnatural death. Associations were not modified by whether the bereaved was blood-related to the deceased or not. CONCLUSIONS: Stigma was perceived more acutely by the relatives and friends of those who died by suicide than those bereaved by other causes of sudden natural or sudden unnatural death. Their high levels of perceived stigma, shame, responsibility and guilt require qualitative investigation to identify whether these grief dimensions limit social functioning, help-seeking behaviour and/or support offered. PMID- 27411750 TI - Complementary and alternative healthcare use by participants in the PACE trial of treatments for chronic fatigue syndrome. AB - BACKGROUND: Chronic Fatigue Syndrome (CFS) is characterised by persistent fatigue, disability and a range of other symptoms. The PACE trial was randomised to compare four non-pharmacological treatments for patients with CFS in secondary care clinics. The aims of this sub study were to describe the use of complementary and alternative medicine (CAM) in the trial sample and to test whether CAM use correlated with an improved outcome. METHOD: CAM use was recorded at baseline and 52weeks. Logistic and multiple regression models explored relationships between CAM use and both patient characteristics and trial outcomes. RESULTS: At baseline, 450/640 (70%) of participants used any sort of CAM; 199/640 (31%) participants were seeing a CAM practitioner and 410/640 (64%) were taking a CAM medication. At 52weeks, those using any CAM fell to 379/589 (64%). Independent predictors of CAM use at baseline were female gender, local ME group membership, prior duration of CFS and treatment preference. At 52weeks, the associated variables were being female, local ME group membership, and not being randomised to the preferred trial arm. There were no significant associations between any CAM use and fatigue at either baseline or 52weeks. CAM use at baseline was associated with a mean (CI) difference of 4.10 (1.28, 6.91; p=0.024) increased SF36 physical function score at 52weeks, which did not reach the threshold for a clinically important difference. CONCLUSION: CAM use is common in patients with CFS. It was not associated with any clinically important trial outcomes. PMID- 27411749 TI - Cognitive functioning in fibromyalgia: The central role of effort. AB - OBJECTIVE: Fibromyalgia syndrome (FM) patients demonstrate deficits in tests of attention, executive functioning and verbal memory. We assessed the role of effort in the cognitive impairment in FM patients, alongside common symptoms of pain, fatigue and depression. METHOD: 50 FM patients underwent a computerized cognitive assessment battery including memory, executive function, attention and information processing speed (NeuroTrax Corp.). Age and education standardized scores were computed. Effort was assessed by the Test of Memory Malingering (TOMM). FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ), Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), a Visual Analog Scale (VAS) of clinical pain and the Beck Depression Inventory (BDI-2). RESULTS: FM patients showed impaired performance on the memory, attention and information processing speed domains. According to the TOMM, sub-optimal effort was shown by 16% of patients. TOMM scores were not associated with pain, fatigue or depression. After controlling for effort, no significant impairment was found in memory scores; however attention and information processing speed scores remained significantly low. Multiple regressions analysis, performed in order to evaluate the contribution of effort, pain, fatigue and depression, found effort to be the only significant variable accounting for variance of cognitive scores on all domains. CONCLUSION: The findings confirm impaired attention and processing speed in FM patients, independent of effort level. Nonetheless, the findings point to a general and strong effect of effort on neuropsychological performance in FM patients, especially in the domain of memory, emphasizes the importance of effort testing in this population. PMID- 27411752 TI - Are the time trends in adolescent psychosomatic problems related to functional impairment in daily life? A 23-year study among 20,000 15-16year olds in Sweden. AB - OBJECTIVE: Worldwide there are frequent reports on increasing psychosomatic problems, anxiety, emotional distress, conduct problems, and depression among adolescents. Recently, it was contended that secular studies on such aspects of adolescent mental health can only be evaluated adequately when data on symptom prevalence are analyzed together with data on functional impairment. Still, this has not yet been done in epidemiological time-trend studies on any aspect of adolescent mental health. Therefore, this study aims to investigate if, and to what extent, changes in adolescents' symptoms of psychosomatic problems are affected when data on functional impairment are taken into account simultaneously. METHODS: A repeated cross-sectional population study relating self-reported symptoms of psychosomatic problems to functional impairment; covering the time-period 1988-2011 and including 19.823 adolescents 15-16years old in eight cohorts in one geographically defined population (Varmland, Sweden). RESULTS: The proportion of adolescents with psychosomatic problems had increased significantly from 1988 to 2005/2008. In all cohorts the proportion of girls with psychosomatic problems was significantly higher than the proportion of boys reporting symptoms. Over the same period, there was a corresponding significant increase of the proportion of participants with symptoms of psychosomatic problems in combination with functional impairment. Adding functional impairment to the measure of psychosomatic problems decreased the prevalence rates, while the shapes of the trend-curves stayed congruent in form. CONCLUSION: The long term pattern of increasing psychosomatic problems among adolescents remains evident, even when taking functional impairment data into account. Previously observed trends of a deteriorating adolescent mental health are thus consistent with this study. PMID- 27411751 TI - Cognitive behaviour therapy for chronic fatigue syndrome: Differences in treatment outcome between a tertiary treatment centre in the United Kingdom and the Netherlands. AB - OBJECTIVE: Cognitive behaviour therapy (CBT) reduces fatigue and disability in chronic fatigue syndrome (CFS). However, outcomes vary between studies, possibly because of differences in patient characteristics, treatment protocols, diagnostic criteria and outcome measures. The objective was to compare outcomes after CBT in tertiary treatment centres in the Netherlands (NL) and the United Kingdom (UK), using different treatment protocols but identical outcome measures, while controlling for differences in patient characteristics and diagnostic criteria. METHODS: Consecutively referred CFS patients who received CBT were included (NL: n=293, UK: n=163). Uncontrolled effect sizes for improvement in fatigue (Chalder Fatigue Questionnaire), physical functioning (SF-36 physical functioning subscale) and social functioning (Work and Social Adjustment Scale) were compared. Multiple regression analysis was used to examine whether patient differences explained outcome differences between centres. RESULTS: Effect sizes differed between centres for fatigue (Cohen's D NL=1.74, 95% CI=1.52-1.95; UK=0.99, CI=0.73-1.25), physical functioning (NL=0.99, CI=0.81-1.18; UK=0.33, CI=0.08-0.58) and social functioning (NL=1.47, CI=1.26-1.69; UK=0.61, CI=0.35 0.86). Patients in the UK had worse physical functioning at baseline and there were minor demographic differences. These could not explain differences in centre outcome. CONCLUSION: Effectiveness of CBT differed between treatment centres. Differences in treatment protocols may explain this and should be investigated to help further improve outcomes. PMID- 27411753 TI - Reporting completeness and transparency of meta-analyses of depression screening tool accuracy: A comparison of meta-analyses published before and after the PRISMA statement. AB - OBJECTIVE: Meta-analyses that are conducted rigorously and reported completely and transparently can provide accurate evidence to inform the best possible healthcare decisions. Guideline makers have raised concerns about the utility of existing evidence on the diagnostic accuracy of depression screening tools. The objective of our study was to evaluate the transparency and completeness of reporting in meta-analyses of the diagnostic accuracy of depression screening tools using the PRISMA tool adapted for diagnostic test accuracy meta-analyses. METHODS: We searched MEDLINE and PsycINFO from January 1, 2005 through March 13, 2016 for recent meta-analyses in any language on the diagnostic accuracy of depression screening tools. Two reviewers independently assessed the transparency in reporting using the PRISMA tool with appropriate adaptations made for studies of diagnostic test accuracy. RESULTS: We identified 21 eligible meta-analyses. Twelve of 21 meta-analyses complied with at least 50% of adapted PRISMA items. Of 30 adapted PRISMA items, 11 were fulfilled by >=80% of included meta-analyses, 3 by 50-79% of meta-analyses, 7 by 25-45% of meta-analyses, and 9 by <25%. On average, post-PRISMA meta-analyses complied with 17 of 30 items compared to 13 of 30 items pre-PRISMA. CONCLUSIONS: Deficiencies in the transparency of reporting in meta-analyses of the diagnostic test accuracy of depression screening tools of meta-analyses were identified. Authors, reviewers, and editors should adhere to the PRISMA statement to improve the reporting of meta-analyses of the diagnostic accuracy of depression screening tools. PMID- 27411754 TI - Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. AB - OBJECTIVE: An increasing number of studies have been conducted to look at anxiety and depression in IBD; however, there is no clear consensus on the prevalence of anxiety and depression in this population. The objective of this systematic review was to compile the existing data on the prevalence of all mood and anxiety disorders in Inflammatory Bowel Disease patients. METHODS: A series of comprehensive literature searches of Medline, Cochrane Library, PsycINFO, CINAHL, Embase, AMED, and ProQuest Dissertations were performed through March 2014. Inclusion criteria included peer-reviewed, published scientific articles that reported a measurement of mood or anxiety among IBD patients. Only studies with adults (>=18years old) and with more than 10 patients were included. Methodological quality was assessed for all included studies. RESULTS: 171 articles were identified with a total of 158,371 participants. Pooled prevalence estimate for anxiety disorders was 20.5% [4.9%, 36.5%] and 35.1% [30.5, 39.7%] for symptoms of anxiety. IBD patients in active disease had higher prevalence of anxiety of 75.6% [65.5%, 85.7%] compared to disease remission. Pooled prevalence of depression disorders was 15.2% [9.9%, 20.5%] and was 21.6% [18.7%, 24.3%] for symptoms of depression. The prevalence of depressive symptoms was higher in Crohn's disease (25.3% [20.7%, 30.0%]) compared to UC, and higher with active disease (40.7% [31.1%, 50.3%]) compared to IBD patients in remission. CONCLUSION: Results from this systematic review indicate that patients with IBD have about a 20% prevalence rate of anxiety and a 15% prevalence rate of depression. PMID- 27411755 TI - Does migration affect the outcome of inpatient psychotherapy? Results from a retrospective cohort study. AB - OBJECTIVE: Reliable data to determine whether migrant patients benefit sufficiently from evidence-based mental health interventions are scarce. Our aim was to examine the effect of migration on the outcome of inpatient psychotherapy. METHODS: We conducted a retrospective cohort study and predicted the course of the global severity index of the Symptom Checklist 90 during therapy based on data from our routine clinical practice (N=542). We used mixed models for our analysis and included relevant clinical characteristics. RESULTS: One hundred and twenty-one patients of our sample had a history of migration which was consistently associated with more symptoms at baseline assessment. Patients with direct experiences of migration had the highest level of symptoms before therapy but also showed the largest decrease of symptoms during therapy (B=-0.09, SD=0.04, p=0.030). This interaction effect could be accounted for by our clinical variables. Patients with indirect experiences of migration did not differ from other patients in their level of improvement (B=-0.05, SD=0.04, p=0.149). CONCLUSION: According to our preliminary data, migration does not seem to negatively affect the outcome of inpatient psychotherapy. Limitations of these promising findings are discussed together with the strong need for more advanced studies in this area of research. PMID- 27411756 TI - A meta-analysis of diagnostic accuracy of three screening tools for insomnia. AB - BACKGROUND: Insomnia is a highly prevalent health complaint in the modern societies; however, insomnia remains under-diagnosed and under-treated. Although screening tools, including the Insomnia Severity Index (ISI), Athens Insomnia Scale (AIS), and Pittsburg Sleep Quality Index (PSQI), are widely used for assessing the risk of insomnia, the diagnostic properties have yet to be summarized in a systematic manner. OBJECTIVES: To estimate and to compare the diagnostic accuracy of the ISI, AIS, and PSQI for insomnia screening. DATA SOURCES: We systematically searched EMBASE, PubMed, PsycINFO, CINAHL and Chinese Electronic Periodic Services for data from their inception to May 20, 2015. DATA SELECTION: Original articles that had assessed the sensitivity and specificity of the ISI, AIS, or PSQI against a reference standard in adult participants (age>18) were included. RESULTS: A total of 19 studies comprising 4693 participants were included. The pooled sensitivity for the ISI, AIS, and PSQI was 88% (95% confidence interval [CI]=0.79 to 0.93), 91% (0.87 to 0.93), and 94% (0.86 to 0.98), respectively. The pooled specificity was 85% (0.68 to 0.94), 87% (0.68 to 0.95), and 76% (0.64 to 0.85); and the pooled DORs was 41.93 (8.77 to 200.33), 67.7 (23.4 to 196.1), and 53 (15.5 to 186.2), respectively. The summary estimates did not differ significantly among the ISI, AIS and PSQI (all P>0.05). CONCLUSIONS: The current evidence indicates that the ISI, AIS, and PSQI yield comparable diagnostic properties for insomnia screening. PMID- 27411757 TI - Eyeworm infections of Oxyspirura petrowi, Skrjabin, 1929 (Spirurida: Thelaziidae), in species of quail from Texas, New Mexico and Arizona, USA. AB - Northern bobwhite (Colinus virginianus) and Scaled quail (Callipepla squamata) have been declining steadily throughout much of their historical range over the past few decades. Even the Rolling Plains of Texas, historically rich with wild quail and one of the last remaining quail strongholds, has been suffering a population decline, most notably since 2010. Gambel's quail (Callipepla gambelii) have also been experiencing their own decline throughout their respective range, but not as significant as that of other species of quail. Eyeworms (Oxyspirura petrowi) in quail have been recognized for years but not thoroughly studied until recently. New research reveals that O. petrowi infection can cause inflammation, oedema, and cellular damage to the eye of the quail host. The objective of this research was to better understand the prevalence of the eyeworm infection in different quail species, expand on known distribution, and determine if there is a relationship between location and species infected with eyeworms. Northern bobwhite, Scaled quail and Gambel's quail were hunter-donated from one county within Texas, New Mexico and Arizona, and examined for the prevalence, mean abundance and mean intensity of eyeworm infection from November 2013 to February 2014. Quail from every location were found to have individuals with a varying degree of eyeworm infection. This is the first study to document eyeworm infection in Gambel's quail and in quail in New Mexico and Arizona, and reports the highest eyeworm infection found in Northern bobwhite and Scaled quail. PMID- 27411759 TI - Anti-fibrotic effects of valproic acid: role of HDAC inhibition and associated mechanisms. AB - Tissue injuries and pathological insults produce oxidative stress, genetic and epigenetic alterations, which lead to an imbalance between pro- and anti-fibrotic molecules, and subsequent accumulation of extracellular matrix, thereby fibrosis. Various molecular pathways play a critical role in fibroblasts activation, which promotes the extracellular matrix production and accumulation. Recent reports highlighted that histone deacetylases (HDACs) are upregulated in various fibrotic disorders and play a central role in fibrosis, while HDAC inhibitors exert antifibrotic effects. Valproic acid is a first-line anti-epileptic drug and a proven HDAC inhibitor. This review provides the current research and novel insights on antifibrotic effects of valproic acid in various fibrotic conditions with an emphasis on the possible strategies for treatment of fibrosis. PMID- 27411760 TI - [Effect of Music Intervention on Maternal Anxiety and Fetal Heart Rate Pattern During Non-Stress Test]. AB - PURPOSE: The purpose of this cross-over experimental study was to examine effects of music intervention on maternal anxiety, fetal heart rate pattern and testing time during non-stress tests (NST) for antenatal fetal assessment. METHODS: Sixty pregnant women within 28 to 40 gestational weeks were randomly assigned to either the experimental group (n=30) or control group (n=30). Music intervention was provided to pregnant women in the experimental group during NST. Degree of maternal anxiety and fetal heart rate pattern were our primary outcomes. State trait anxiety inventory, blood pressure, pulse rate, and changes in peripheral skin temperature were assessed to determine the degree of maternal anxiety. Baseline fetal heart rate, frequency of acceleration in fetal heart rate, fetal movement test and testing time for reactive NST were assessed to measure the fetal heart rate pattern. RESULTS: The experimental group showed significantly lower scores in state anxiety than the control group. There were no significant differences in systolic blood pressure and pulse rate between the two groups. Baseline fetal heart rate was significantly lower in the experimental group than in the control group. Frequency of acceleration in fetal heart rate was significantly increased in the experimental group compared to the control group. There were no significant differences in fetal movement and testing time for reactive NST between the two groups. CONCLUSION: Present results suggest that music intervention could be an effective nursing intervention for alel viating anxiety during non-stress test. PMID- 27411761 TI - [The Structural Equation Model on Resilience of Breast Cancer Patients Receiving Chemotherapy]. AB - PURPOSE: The purpose of this study was to construct and test a structural equation model on resilience of breast cancer patients receiving chemotherapy. METHODS: Participants were 204 patients with breast cancer who received chemotherapy treatment. They participated in a structured interview, which included social support, depression, symptom experience, self-efficacy, hope, resilience, and infection prevention behaviors. Data were analyzed using SPSS/WIN 20.0 and AMOS 18.0. RESULTS: Lower depression (gamma=-.33, p=.020) and symptom experience (gamma=-.31, p=.012) and higher self-efficacy (gamma=.32, p=.005) and hope (gamma=.48, p=.016) were influenced by higher social support. Greater resilience was influenced by lower symptom experience (beta=-.18, p=.016), higher self-efficacy (beta=.49, p=.023), and higher hope (beta=.46, p=.012), and these predictors explained 66.7% of variance in resilience. Greater resilience (beta=.54, p=.009) made an impact on greater infection prevention behaviors. Resilience mediated the relations of symptom experience (beta=-.10 p=.013), self efficacy (beta=.27, p=.006) and hope (beta=.25, p=.009) with infection prevention behaviors. These predictors explained 24.9% of variance in infection prevention behaviors. CONCLUSION: The findings of the study suggest that breast cancer patientsw ith greater resilience who are receiving chemotherapy participate in increased infection prevention behaviors. Further research should be conducted to seek intervention strategies that improve breast cancer patients' resilience. PMID- 27411762 TI - [Influence of Nurses' Self-leadership on Individual and Team Members' Work Role Performance]. AB - PURPOSE: The purpose of this study was to examine correlations between nurses' self-leadership and individual work role performance and correlations between self-leadership in nursing units and team members' work role performance. METHODS: Participants were 202 conveniently selected general nurses from 5 general hospitals in Korea. The study was carried out on 35 nursing units. Data were collected during February 2015 with self-report questionnaires. RESULTS: For factors affecting individual work role performance, self-expectation, self-goal setting, constructive thought, clinical career in the present nursing unit and marital status accounted for 44.0% of proficiency, while self-expectation, self goal setting, constructive thought, and marital status accounted for 42.3% of adaptivity. Self-expectation, self-goal setting, constructive thought, self reward, clinical career in the present nursing unit and position accounted for 26.4% of proactivity. In terms of team members' work role performance, self reward and self-expectation in nursing units explained 29.0% of team members' proficiency. Self-reward and self-expectation in nursing units explained 31.6% of team members' adaptivity, and self-reward in nursing units explained 16.8% of team members' proactivity. CONCLUSION: The results confirm that nurses' self leadership affects not only individual self-leadership but also team members' work role performance. Accordingly, to improve nurses' work role performance in nursing units of nursing organizations, improvement in nursing environment based on self-leadership education is necessary and nurses' tasks rearranged so they can appreciate work-autonomy and challenges of work. PMID- 27411763 TI - [Development and Effects of a Cognitive-behavioral Therapy Based Program in Reducing Internalized Stigma in Patients with Schizophrenia]. AB - PURPOSE: This study was done to develop a internalized stigma reducing program based on cognitive-behavioral therapy and appropriate for patients with schizophrenia and to evaluate its effectiveness. METHODS: The study design was a mixed method research. Qualitative study, 13 patients with schizophrenia who had experience in overcoming stigma were purposively chosen for interviews and data were analyzed using Giorgi method. Quantitative study, 64 patients with schizophrenia (experimental group=32, control group=32) were recruited. The cognitive-behavioral therapy-based program for reducing internalized stigma in patients with schizophrenia was provided for 8 weeks (12 sessions). Data were collected from June. 20, 2013 to Feb. 14, 2014. Quantitative data were analyzed using chi2-test, t-test, repeated measures ANOVA with the SPSS program. RESULTS: Qualitative results, from the experience of coping with stigma in patients with schizophrenia seventeen themes and five themes-clusters were drawn up. Quantitative results showed that internalized stigma, self-esteem, mental health recovery and quality of life were significantly better in the experimental group compared to the control group. CONCLUSION: Study findings indicate that this program for reducing internalized stigma in patients with schizophrenia is effective and can be recommended as a rehabilitation program intervention to help patients with schizophrenia to cope with internalized stigma. PMID- 27411764 TI - [Influences of Hospital Nurses' perceived reciprocity and Emotional Labor on Quality of Nursing Service and Intent to Leave]. AB - PURPOSE: This study was performed to investigate the relationship among reciprocity, emotional labor, nursing service quality and intent to leave, and to identify factors influencing nursing service quality and intent to leave. METHODS: This study was a cross-sectional survey. Participants were 300 nurses working at five general hospitals in two provincial cities in Gyeongsang Province, Korea. From May 1 to June 30, 2014, data were collected using structured questionnaires and analyzed with SPSS/PC ver 20.0 programs. RESULTS: There were relationships between reciprocity and nursing service quality, and intent to leave, and between emotional labor and intent to leave. Participants' general characteristics, reciprocity and emotional labor explained 48.4% of variance in nursing service quality and participants' general characteristics and these two independent variables explained 31.9% of intent to leave. CONCLUSION: These findings indicate that from the perception of hospital nurses, reciprocity and emotional labor are both very important factors to improve the quality of nursing service and decrease the intent to leave. So nursing managers should try to develop various personnel management programs focused on human emotions, and create a mutual respectable organizational culture and work environment. PMID- 27411765 TI - [A Study on the Classification of Nursing Management Competencies and Development of related Behavioral Indicators in Hospitals]. AB - PURPOSE: The aim of this study was to classify nursing management competencies and develop behavioral indicators for nurse managers in hospitals. Also, levels of importance and performance based on developed criteria were to be identified and compared. METHODS: Using expert survey we classified nursing management competencies and behavioral indicators with data from 34 nurse managers and professors. Subsequently, data from a survey of 216 nurse managers in 7 cities was used to analyze the importance-performance comparison of the classified nursing management competencies and behavioral indicators. RESULTS: Forty-two nursing management competencies were identified together with 181 behavioral indicators. The mean score for importance of nursing management competency was higher than the mean score for performance. According to the importance performance analysis, 5 of the 42 nursing management competencies require further development: vision-building, analysis, change management, human resource development, and self-management competency. CONCLUSION: The classification of nursing management competencies and behavioral indicators for nurse managers in hospitals provides basic data for the development and evaluation of programs designed to increase the competency of nurse managers in hospitals. PMID- 27411766 TI - [Effect of Smartphone Apps Applying BodyThink Program on Obesity in Adolescent Girls]. AB - PURPOSE: The purpose of this study was to determine the effects of smartphone apps applying BodyThink program on BMI, percentage of body fat, skeletal muscle rate, body image, and self-esteem of adolescent girls. METHODS: Sixty-eight high school girls with a BMI of over 25kg/m2 were recruited to participate in this study. Girls from four schools were divided into two groups: the experimental group, which used the smartphone apps applying BodyThink program, and the control group, which used smartphone apps and small group counseling. The experimental group received the BodyThink program 6 times, scheduled once a week, with each session lasting 40~50 minutes. Test measures were completed before and after the 6 week intervention period for all participants. Collected data was analyzed using Shapiro-Wilk test, descriptive statistics, chi2 test, independent t-test, Mann-Whitney U test with the SPSS/WIN 18.0 program. RESULTS: The girls in the experimental group significantly improved their results in BMI(Z=-1.67, p=.042), percentage of body fat (Z=-3.01, p=.001), skeletal muscle rate (t=-3.50, p<.001), and self-esteem (t=2.66, p=.005) after the program, compared to the girls in the control group. CONCLUSION: Mobile applications applying psychological and emotional intervention programs have the potential to be effective alternative methods to improve the body composition and self-esteem of obese adolescent girls. PMID- 27411767 TI - [Frequency, Intensity and Daily Life Distress of Urinary Dysfunction in Women with Cervical Cancer after Radical Hysterectomy]. AB - PURPOSE: This study was done to identify frequency, intensity of urinary dysfunction and daily life distress in women after a radical hysterectomy for cervical cancer. METHODS: One hundred and fifty seven women who had undergone a radical hysterectomy and one hundred and sixty five women as healthy controls completed questionnaires on intensity of urinary dysfunction and daily life distress caused by urinary dysfunction. RESULTS: Women with cervical cancer showed higher frequency of urinary dysfunction than healthy controls. Major urinary dysfunction for women with cervical cancer in order of frequency were night-time incontinence (odds ratio=10.39, p<.001), difficulty in starting urination, weak urine stream and sense of incomplete emptying of bladder. The highest score on intensity was difficulty in starting urination, followed by urgency, weak urine stream, daytime frequency and sense of incomplete emptying. Night-time incontinence was the urinary symptom causing the most daily life distress for cervical cancer women followed by difficulty in starting urination, urgency, sense of incomplete emptying, and night-time frequency. CONCLUSION: Results suggest that nurses should address the potential postoperative urinary complications and develop long term interventions to decrease urinary dysfunction and daily life distress for women who have had a radical hysterectomy for cervical cancer. PMID- 27411768 TI - [Effects of Breastfeeding Empowerment Program on Breastfeeding Self-efficacy, Adaptation and Continuation in Primiparous Women]. AB - PURPOSE: The purpose of this study was to develop a breastfeeding empowerment program and to investigate the effects of the breastfeeding empowerment program on self-efficacy, adaptation and continuation of breastfeeding for primiparous women. METHODS: The 5 session breastfeeding empowerment program was developed and a non-equivalent control group non-synchronized quasi-experiment design was used. Fifty-five participants were assigned to either the experimental group (n=27) or the control group (n=28). Effects were tested using repeated measures ANOVA and chi2-test. RESULTS: Scores for self-efficacy, adaptation and continuation of breastfeeding of in the experimental group after program were significantly higher than 1 week, 4 weeks, 8 weeks scores in control group. CONCLUSION: The effects of the breastfeeding empowerment program for elevating self-efficacy, adaptation and continuation of breastfeeding in primiparous women were validated. Therefore, this program can be recommended for vigorous use in clinical practice. PMID- 27411770 TI - [Validity and Reliability of the Peer Group Caring Interaction Scale-Korean Version]. AB - PURPOSE: This paper was conducted to validate the Korean version of the Peer Group Caring Interaction Scale (PGCIS-K) that measures caring behaviors as experienced by nursing students. METHODS: Translation of the PGCIS-K was validated through forward-backward translation methods. Survey data were collected from 218 nursing students in a nursing school. Construct validity and criterion-related validity were evaluated. Internal consistency and the Guttman split-half coefficient were calculated to assess reliability. RESULTS: The PGIS-K showed reliability except for 4 items (Cronbach's alpha=.91, Guttman split-half coefficient=.85), which were low (<.30) or negatively correlated with the total scale. A 12-item reduced form of the PGCIS-K was developed by item-analysis and construct validity evidence. Factor loading for the 12 items on 2 factors ranged from .47~.82, which explained 58.4% of the total variance. Two factors were named 'modeling and assistance (Cronbach's alpha=.87)' and 'communication and sharing (Cronbach's alpha=.82)'. Convergent validity, discriminant validity, and criterion validity were supported according to the correlation coefficients of the 2 factors with other measure. CONCLUSION: The findings suggest preliminary evidence that the 12-item PGCIS-K can be used to measure nursing students' peer group caring interactions in Korea. Additional studies are recommended to continue the psychometric evaluation of this scale. Also, it can be extended to measure graduate nursing students or staff nurses' peer group caring interaction. PMID- 27411769 TI - [Effect of Cancer Symptoms and Fatigue on Chemotherapy-related Cognitive Impairment and Depression in People with Gastrointestinal Cancer]. AB - PURPOSE: The purpose of this study was to test a hypothetical model of chemotherapy-related cognitive impairment (CRCI) and depression in people with gastrointestinal cancer. METHODS: A purposive sample of 198 patients undergoing chemotherapy was recruited from November 2014 to July 2015. The instruments were Everyday Cognition (ECog), Hospital Anxiety Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and M. D. Anderson Symptom Inventory-Gastrointestinal Cancer Module. Data were analyzed using descriptive statistics, correlation, and path analysis. RESULTS: CRCI was directly affected by cancer symptoms (beta=.19, p=.004) and fatigue (beta=.56, p<.001)(R2=47.2%). Depression was directly affected by fatigue (beta=.48, p<.001) and CRCI (beta=.27, p<.001). However, The impact of cancer symptoms on depression was confirmed through the mediating effect of CRCI. CONCLUSION: Results indicate that in patients with gastrointestinal cancer undergoing chemotherapy along with the direct physiologic effects (fatigue, symptoms) of cancer treatment may have altered cognitive function leading to depression. PMID- 27411771 TI - [Concept Analysis for Psychological Insulin Resistance in Korean People with Diabetes]. AB - PURPOSE: The purpose of this study was to define the concept for psychological insulin resistance in the Korean population with diabetes. METHODS: The Hybrid model was used to perform the concept analysis of psychological insulin resistance. Results from both the theoretical review with 26 studies and a field study including 19 participants with diabetes were included in final process. RESULTS: The preceding factors of psychological insulin resistance were uncontrolled blood glucose and change in daily life. The concept of psychological insulin resistance was found to have three categories with 8 attributes such as emotional factors (negative feeling), cognitive factors (low awareness and knowledge, low confidence for self-injection) and supportive factors (economic burden, dependency life, embarrassing, feeling about supporters, feeling of trust in, vs mistrust of health care providers). The 8 attributes included 30 indicators. CONCLUSION: The psychological insulin resistance of population with diabetes in Korea was defined as a complex phenomenon associated with insulin therapy that can be affected by emotional factors, cognitive factors, and supportive relational factors. Based on the results, a tool for measuring psychological insulin resistance of Koreans with diabetes and effective programs for enhancing insulin adherence should be developed in future studies. PMID- 27411772 TI - [Factors Influencing Posttraumatic Growth in Survivors of Breast Cancer]. AB - PURPOSE: Posttraumatic growth (PTG) is defined as 'positive psychological change experienced as a result of a struggle with highly challenging life circumstances'. The purpose of this study was to identify the level of PTG and its correlates in Korean patients with breast cancer. METHODS: A sample of 120 participants was recruited from outpatients, who had successfully completed primary treatment of breast cancer at a university hospital., Data were collected from June to December, 2014 using Posttraumatic Growth Inventory, lllness Intrusiveness Rating Scale, Cancer Coping Questionnaire, Revised Life Orientation Test and The Multidimensional Scale of Perceived Social Support. RESULTS: Total score for the PTG was 79.18+/-17.54 in patients surviving breast cancer. Bivariate analyses indicated that PTG was positively associated with having a religion, perceived social support, greater optimism, cancer coping, and illness intrusiveness. Results of the regression analysis showed that cancer coping (beta=.29, p=.001), optimism (beta=0.28, p=.001) and illness intrusiveness (beta=0.17, p=.037) were statistically significant in patients' PTG. CONCLUSION: The research findings show that the variables of cancer coping, optimism and illness intrusiveness significantly explain PTG and these psychological variables can be used to provide improvement in PTG for patients with breast cancer. PMID- 27411773 TI - The Effect of Patient-centered CPR Education for Family Caregivers of Patients with Cardiovascular Diseases. AB - PURPOSE: For cardiovascular patients, family caregivers play a vital role in daily nursing and cardiac emergencies. This study aimed to evaluate the effect of patient-centered CPR education (PCE) for family caregivers of patients with cardiovascular diseases. METHODS: Fifty-four participants were randomly assigned to the PCE or control group. The PCE group received tailored counseling on overall cardiovascular disease information and CPR followed by interactive instructor-guided CPR training and re-education follow-up by telephone 2 weeks later. The control group received only video-based CPR self-education and booklets. Cardiovascular disease and CPR knowledge and self-efficacy were measured before (pre-test), immediately after (post-test 1), and 4 weeks after the PCE (post-test 2). CPR skills and performance were measured pre-test and at post-test1. RESULTS: The PCE group demonstrated significant improvements in knowledge (F=91.09, p<.001), self-efficacy (F=15.19, p<.001) and CPR skills and performance (F=8.10, p=.008), as well as significant differences over time (knowledge: F=364.25, p<.001; self-efficacy: F=1162.28, p<.001; CPR skills and performance: F=1798.81, p<.001). There were significant group-by-time interactions for knowledge (F=8.10, p=.001), self-efficacy (F=4.30, p=.019) and CPR skills and performance (F=4.81, p=.036) by repeated measures ANOVA. CONCLUSION: This is the first study to demonstrate the effects of a patient centered intervention with CPR education tailored for patients' and family caregivers' preferences, needs, and lifestyles. The results of this study encourage the use of tailored, patient-centered interventions in cardiovascular nursing practice. PMID- 27411774 TI - Assessment of bleeding risk in acute ill medical patients. An essential part of venous thromboembolism prevention. PMID- 27411775 TI - Rapid and Selective Detection of Pathogenic Bacteria in Bloodstream Infections with Aptamer-Based Recognition. AB - Sepsis and bacteremia are life-threatening clinical syndromes associated with significant patient morbidity and mortality. Rapid and sensitive detection of pathogenic bacteria is the key to improve patient survival rates. Herein, we have rationally constructed a simple aptamer-based capture platform to shorten the time needed for confirmation of bacterial bloodstream infection in clinical blood samples. This capture platform is made of a mesoporous TiO2-coated magnetic nanoparticle and is modified with target aptamer. It features excellent bacterial enrichment efficiency of about 80% even at low bacterial concentrations (10-2000 CFU mL(-1)). More importantly, the bacteria can be enriched within 2 h, and the time for bacterial identification is effectively shortened in comparison to the "gold standard" in clinical diagnosis of bloodstream infection. The aptamer-based capture platform may pave a way for the detection of biomarkers and find potential applications in disease diagnosis. PMID- 27411776 TI - Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine. AB - Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (C.albicans). Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra amniotic C.albicans infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra amniotic C.albicans infection. Pregnant sheep received intra-amniotic injections with 10(7) colony-forming units C.albicans or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of C.albicans. Intra-amniotic C.albicans caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3(+) lymphocytes, MPO(+) cells and elevated TNF-alpha and IL-17 mRNA levels. Fluconazole treatment in utero decreased intestinal C.albicans colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic C.albicans caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate C.albicans-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy. PMID- 27411778 TI - Plasmonic Effect on Exciton and Multiexciton Emission of Single Quantum Dots. AB - Quantum dots are nanoscale quantum emitters with high quantum yield and size dependent emission wavelength, holding promises in many optical and electronic applications. When quantum dots are situated close to noble metal nanoparticles, their emitting behavior can be conveniently tuned because of the interaction between the excitons of the quantum dots and the plasmons of the metal nanoparticles. This interaction at the single quantum dot level gives rise to reduced or suppressed photoluminescence blinking and enhanced multiexciton emission, which is difficult to achieve in isolated quantum dots. However, the mechanism of how plasmonic structures cause the changes in the quantum dot emission remains unclear. Because of the complexity of the system, the interfaces between metal, semiconductor, and ligands must be considered, in addition to factors such as geometry, interparticle distance, and spectral overlap. The challenges in the design and fabrication of the hybrid nanostructures as well as in understanding the exciton-plasmon coupling mechanism can be overcome by a cooperative effort in synthesis, optical spectroscopy, and theoretical modeling. PMID- 27411777 TI - The High Risk of Contrast-induced Nephropathy in Patients with Suspected Pulmonary Embolism Despite Three Different Prophylaxis: A Randomized Controlled Trial. AB - OBJECTIVE: The objective was to compare the protective effects of N acetylcysteine (NAC) plus normal saline (NS), sodium bicarbonate (NaHCO3 ) plus NS, and NS alone in the prevention of contrast-induced nephropathy (CIN) after computed tomography pulmonary angiography (CTPA) in emergency patients. METHODS: This study was planned as a randomized, controlled clinical research. Patients undergoing contrast-enhanced CTPA on suspicion of pulmonary embolism (PE) in the emergency department and with at least one risk factor for development of CIN were included in one of three different prophylaxis groups. The groups received 3 mL/kg intravenous (IV) NAC+NS or NaHCO3 +NS solution or NS alone 1 hour before CTPA and 1 mL/kg IV per hour for a minimum of 6 hours after CTPA. CIN was evaluated as the primary outcome and moderate or severe renal insufficiency and in-hospital mortality as secondary outcomes. RESULTS: A total of 257 patients were enrolled in the study. The total level of CIN development was 23.7% (61/257), the level of moderate and severe renal failure was 12.5% (32/257), and the in-hospital mortality rate was 12.8% (33/257). Rates of CIN development in the drug groups were 23.5% in the NAC group (20/85), 21.2% (18/85) in the NaHCO3 group, and 26.4% in the NS group (23/87). Rates of development of moderate or severe renal insufficiency were 9.4% in the NAC group (8/85), 10.6% in the NaHCO3 group (9/85), and 17.2% in the NS group (15/87). In-hospital mortality rates were 12.9% in the NAC group (11/85), 11.8% in the NaHCO3 group (10/85), and 13.8% in the NS group (12/87). No difference was determined between the drug groups in terms of CIN, moderate or severe renal injury, or hospital mortality. CONCLUSIONS: Our results indicate that there is a high risk of CIN in patients with suspected PE despite three different types of prophylaxis being administered, and no statistically significant differences were observed among prophylactic NAC, NaHCO3 , and NS in prevention of CIN following contrast enhanced CTPA. PMID- 27411779 TI - Coffee consumption and mortality in three Eastern European countries: results from the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study. AB - OBJECTIVE: To test the association between coffee consumption and risk of all cause, CVD and cancer death in a European cohort. DESIGN: Prospective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used. SETTING: Czech Republic, Russia and Poland. SUBJECTS: A total of 28561 individuals followed for 6.1 years. RESULTS: A total of 2121 deaths (43.1 % CVD and 35.7 % cancer mortality) occurred during the follow-up. Consumption of 3-4 cups coffee/d was associated with lower mortality risk in men (HR=0.83; 95 % CI 0.71, 0.99) and women (HR=0.63; 95 % CI 0.47, 0.84), while further intake showed non-significant reduced risk estimates (HR=0.71; 95 % CI 0.49, 1.04 and HR=0.51; 95 % CI 0.24, 1.10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0.71; 95 % CI 0.54, 0.93) for consumption of 3-4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0.61; 95 % CI 0.43, 0.87) and cancer mortality (HR=0.59; 95 % CI 0.35, 0.99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake. CONCLUSIONS: Coffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed. PMID- 27411780 TI - Improved learning of sequential behaviour during cane gait training or stair climbing after femoral neck fracture: an implication for donepezil for very mild Alzheimer's disease. PMID- 27411781 TI - The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors. AB - We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 MUg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps. PMID- 27411783 TI - Tomato plants increase their tolerance to low temperature in a chilling acclimation process entailing comprehensive transcriptional and metabolic adjustments. AB - Low temperature is a major environmental stress that seriously compromises plant development, distribution and productivity. Most crops are from tropical origin and, consequently, chilling sensitive. Interestingly, however, some tropical plants, are able to augment their chilling tolerance when previously exposed to suboptimal growth temperatures. Yet, the molecular and physiological mechanisms underlying this adaptive process, termed chilling acclimation, still remain practically unknown. Here, we demonstrate that tomato plants can develop a chilling acclimation response, which includes comprehensive transcriptomic and metabolic adjustments leading to increased chilling tolerance. More important, our results reveal strong resemblances between this response and cold acclimation, the process whereby plants from temperate regions raise their freezing tolerance after exposure to low, non-freezing temperatures. Both chilling and cold acclimation are regulated by a similar set of transcription factors and hormones, and share common defence mechanisms, including the accumulation of compatible solutes, the mobilization of antioxidant systems and the rearrangement of the photosynthetic machinery. Nonetheless, we have found some important divergences that may account for the freezing sensitivity of tomato plants. The data reported in this manuscript should foster new research into the chilling acclimation response with the aim of improving tomato tolerance to low temperature. PMID- 27411784 TI - Inflexible ethanol intake: A putative link with the Lrrk2 pathway. AB - Alcoholism is a complex multifactorial disorder with a strong genetic influence. Although several studies have shown the impact of high ethanol intake on the striatal gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with the two major concerns in addiction: the excessive drug consumption and relapsing. In this study, we used a chronic three-bottle free-choice murine model to address striatal transcript regulation among animals with different ethanol intakes and preferences: Light Drinkers (preference for water throughout the experiment), Heavy Drinkers (preference for ethanol with a non-compulsive intake) and Inflexible Drinkers (preference for ethanol and simultaneous loss of control over the drug intake). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the striatum, a brain region critical for the development of alcohol addiction. We found that the transcripts of the Lrrk2 gene, which encodes a multifunctional protein with kinase and GTPase activities, is upregulated only in Inflexible Drinkers suggesting, for the first time, that the Lrrk2 pathway plays a major role in the compulsive ethanol intake behaviour of addicted subjects. PMID- 27411785 TI - Measuring eye states in functional MRI. AB - BACKGROUND: In many functional magnetic resonance imaging (fMRI) studies, experimental design often depends on the eye state (i.e., whether the participants had their eyes open or closed). Closed eyes during an fMRI is the general convention, particularly when patients are in a resting-state, but the eye state is difficult to verify. Although knowledge of the impact of the eye state on brain activity is steadily growing, only a few research groups have implemented standardized procedures to monitor eye movements and eye state. These procedures involve advanced methods that are costly (e.g., fMRI-compatible cameras) and often time-consuming (e.g., EEG/EOG). RESULTS: We present a simple method that distinguishes open from closed eyes utilizing functional MR images alone. The utility of this method was demonstrated on fMRI data from 14 healthy subjects who had to open and close their eyes according to a predetermined protocol (3.0 T MRI scanner, EPI sequence with 3 * 3 * 3 mm voxels, TR 2.52 s). CONCLUSION: The method presented herein is capable of extracting the movement direction of the eyes. All described methods are applicable for pre- and post normalized MR images and are freely available through a MATLAB toolbox. PMID- 27411787 TI - Measles. PMID- 27411786 TI - Prevention of vocal fold scarring by local application of basic fibroblast growth factor in a rat vocal fold injury model. AB - OBJECTIVES/HYPOTHESIS: Vocal fold scarring, which causes severe hoarseness, is intractable. The optimal treatment for vocal fold scarring has not been established; therefore, prevention of scarring is important. The aim of this study was to clarify the effectiveness of basic fibroblast growth factor (bFGF) for prevention of postsurgical vocal fold scarring. STUDY DESIGN: Prospective animal experiments with controls. METHOD: The vocal folds of Sprague-Dawley rats were injured unilaterally or bilaterally after local application of a 10 MUL solution of bFGF. Larynges ware harvested for histological and immunohistochemical examination 2 months postoperation and for quantitative real time polymerase chain reaction (qRT-PCR) analysis 1 week postoperation. RESULTS: Histological examination showed significantly increased hyaluronic acid and decreased deposition of dense collagen in the bFGF-treated group at 100 ng/10 MUL compared with the sham-treated group. Immunohistochemical examination showed significantly decreased collagen type III deposition in the bFGF-treated group at 100 ng/10 MUL compared with the sham-treated group. qRT-PCR revealed that hyaluronan synthase 2 (Has2), Has3, and hepatocyte growth factor were upregulated in bFGF-treated groups compared with sham-treated group. CONCLUSION: The current results suggest that local application of bFGF at the time of injury has the potential to prevent vocal fold scarring. Preventive injection of bFGF could be applied at the time of phonomicrosurgery to avoid postoperative scar formation. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016 127:E67-E74, 2017. PMID- 27411788 TI - A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol). AB - BACKGROUND: Five to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. DESIGN AND METHODS: The SECURE-trial is designed as a multicenter, randomized, parallel arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy. Patients in the usual care group will be treated according to the physician's knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3 monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months. The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients' symptoms and treatment and work performance, and ultimately, cost-effectiveness. DISCUSSION: The SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012) TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022 http://www.zonmw.nl/nl/projecten/project detail/scrutinizing-inefficient-use-of-cholecystectomy-a-randomized-trial concerning-variation-in-practi/samenvatting/. PMID- 27411789 TI - Lost in translation: a focus group study of parents' and adolescents' interpretations of underage drinking and parental supply. AB - BACKGROUND: Reductions in underage drinking will only come about from changes in the social and cultural environment. Despite decades of messages discouraging parental supply, parents perceive social norms supportive of allowing children to consume alcohol in 'safe' environments. METHODS: Twelve focus groups conducted in a regional community in NSW, Australia; four with parents of teenagers (n = 27; 70 % female) and eight with adolescents (n = 47; 55 % female). Participants were recruited using local media. Groups explored knowledge and attitudes and around alcohol consumption by, and parental supply of alcohol to, underage teenagers; and discussed materials from previous campaigns targeting adolescents and parents. RESULTS: Parents and adolescents perceived teen drinking to be a common behaviour within the community, but applied moral judgements to these behaviours. Younger adolescents expressed more negative views of teen drinkers and parents who supply alcohol than older adolescents. Adolescents and parents perceived those who 'provide alcohol' (other families) as bad parents, and those who 'teach responsible drinking' (themselves) as good people. Both groups expressed a preference for high-fear, victim-blaming messages that targeted 'those people' whose behaviours are problematic. CONCLUSIONS: In developing and testing interventions to address underage drinking, it is essential to ensure the target audience perceive themselves to be the target audience. If we do not have a shared understanding of underage 'drinking' and parental 'provision', such messages will continue to be perceived by parents who are trying to do the 'right' thing as targeting a different behaviour and tacitly supporting their decision to provide their children with alcohol. PMID- 27411790 TI - EHD1 confers resistance to cisplatin in non-small cell lung cancer by regulating intracellular cisplatin concentrations. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most aggressive types of cancer. However, resistance to cisplatin (CDDP) remains a major challenge in NSCLC treatment. The purpose of this study was to investigate the ability of EHD1 [Eps15 homology (EH) domain - containing protein 1] to confer CDDP resistance in NSCLC cells and to investigate mechanisms of this resistance. METHODS: The associations between EHD1 expression in NSCLC specimens and clinicopathological features, including prognosis, were assessed by immunohistochemistry (IHC). Using DNA microarrays, we performed a genome-wide analysis of cisplatin-resistant NSCLC cells to identify the involvement of the EHD1 gene in this resistance. We overexpressed and knocked down EHD1 in cell lines to investigate the effect of this gene on proliferation and apoptosis. A quantitative analytical method for assessing CDDP in cells was developed. High performance liquid chromatography was used to measure the concentration of cisplatin in cells. RESULTS: The immunohistochemistry assay showed that adjuvant chemotherapy-treated NSCLC patients expressing EHD1 exhibited reduced OS compared with patients who did not express EHD1 (P = 0.01). Moreover, DNA microarrays indicated that the EHD1 gene was upregulated in CDDP- resistant NSCLC cells. The IC50 value of CDDP in cells that overexpressed EHD1 was 3.3-fold greater than that in the A549-control line, and the IC50 value of EHD1 knockdown cells was at least 5.2-fold lower than that of the control cells, as evidenced by a CCK-8 assay. We found that the percentage of early apoptotic cells was significantly decreased in A549-EHD1 cells, but the rates of early apoptosis were higher in the EHD1 knockdown cell line than in the A549/DDP control line, as indicated by a flow cytometry analysis. High-performance liquid chromatography (HPLC) showed that the total platinum level was lower in A549-EHD1 cells than in control cells, and the concentration of CDDP was higher in the EHD1 knockdown cells than in the A549/DDP control cells. CONCLUSION: We conclude that EHD1 is required for tumour growth and that it is a regulator of CDDP accumulation and cytotoxicity. The selective knockdown of EHD1 in tumours offers a strategy for enhancing the efficacy of CDDP. PMID- 27411791 TI - [Unclear liver lesions in a 19-year-old woman with acute myeloid leukemia]. AB - A 19-year old woman with acute myeloid leukemia presented with newly observed liver lesions during ongoing consolidation therapy. Due to unexplained cholestasis during induction, biliary duct drainage was performed. Microbiologic and histologic examinations revealed the presence of atypical mycobacteria, namely Mycobacterium abscessus. With an appropriate antiinfective regime which was continuously administered using a portable pump in the outpatient setting, further mycobacterial spread during simultaneous chemotherapy-associated neutropenia was prevented. Despite multiple bacterial resistance mechanisms, proper treatment of leukemia with curative intention could be ensured. PMID- 27411792 TI - [Extracorporeal membrane oxygenation : Principles and medical indications]. AB - Extracorporeal membrane oxygenation (ECMO) is a special form of a miniaturized heart-lung machine with the ultimate goal to stabilize critically ill patients. Dependent on the cannulation strategy ECMO can support or replace heart and/or lung function. Medical indications and contraindications have to be evaluated thoroughly before cannulation. Moreover, before ECMO initiation a solid treatment aim has to be defined: bridge to recovery, bridge to decision, bridge to transplantation, and bridge to destination (i. e. implantation of a permanent assist device). Regarding invasiveness of the system, potential life-threatening complications, requirement of standardized monitoring of the patient and the device as well as tertiary care infrastructure, ECMO should exclusively be used in highly experienced tertiary centers. PMID- 27411793 TI - Cognitive Evaluation and Quality of Life Assessment in Patients with Subjective Tinnitus. PMID- 27411794 TI - Association between Lymphotoxin Alpha (-252G/A and -804C/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis. AB - PURPOSE: Lymphotoxin-Alpha (LTA) is a mediator of inflammation which may be associated with the risk of ischemic stroke (IS). Polymorphisms (-252A/G and 804C/A) in the LTA gene have been found to be associated with IS with contradictory results. The present meta-analysis aimed to provide a comprehensive account of the association of (-252A/G and -804C/A) gene polymorphisms of LTA gene with susceptibility to IS. METHODS: A literature search for eligible candidate gene studies published before April 20, 2015 was conducted in the PubMed, EMBASE, Trip database and Google Scholar. The following combinations of main keywords were used: ('Lymphotoxin-alpha' or 'LTA' or 'tumour necrosis factor beta' or 'TNF-beta') and ('Ischemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Fixed or random effects models were used to estimate the strength of association through Odds ratios (ORs) and 95% confidence interval (CI). RESULTS: Four case-control studies for LTA -252A/G gene polymorphism showed no significant association under; dominant (OR, 0.9; 95% CI; 0.8 to 1.0, P value 0.34), recessive (OR, 1.1; 95% CI; 0.9 to 1.3; P value 0.21) models, indicating that GG and AG genotypes may not possibly confer an increased susceptibility to IS as compared to AA genotype. For LTA -804C/A gene polymorphism, three casecontrol studies also showed no significant association under; dominant (OR, 0.5; 95% CI; 0.1 to 2.3; P value 0.44), recessive (OR, 0.8; 95% CI; 0.38 to 2.07, P value 0.79) models with IS risk. CONCLUSION: Based on ethnicity stratification, our meta-analysis suggests that LTA -252A/G gene polymorphism is found to be significantly associated with the risk of IS in Caucasian population, but not in Asian population. However, LTA -804C/A gene polymorphism is not found to be associated with the susceptibility of IS in both Asian as well as in Caucasian population. Further well designed large sample size prospective studies are needed to confirm these findings. PMID- 27411795 TI - Acute Myeloid Leukemia with Initial Presentation of Facial Palsy and Exophthalmos. PMID- 27411796 TI - Hypoxic Corpus Callosum Lesion after Cardiac Arrest with Good Prognosis. AB - Hypoxic ischemic damage of the corpus callosum after cardiac arrest is a rare condition. Lesions of the splenium of the corpus callosum after hypoxia are bilateral and lead to poor prognosis. Herein, we present a case with good prognosis after cardiac arrest with bilateral lesions of the splenium of corpus callosum. PMID- 27411797 TI - Massive Spontaneous Symptomatic Hemorrhagic Transformation Following Pontine Infarction - A Case Report. AB - PURPOSE: Spontaneous hemorrhagic transformation is common in anterior circulation infarction, but is rarely seen in brainstem infarction. We report a case of massive symptomatic brainstem hemorrhagic transformation in a patient with pontine infarction treated with only antiplatelet agents. CASE REPORT: A 59-year old man presented with acute dysarthria and right sided weakness. His Glasgow coma scale was E3 V5 M6. His pupils were pinpoint in size and minimally reactive to light. He showed complete horizontal gaze palsy, right facial weakness, severe dysarthria, dysphagia, and right hemiplegia. Computed tomography showed a dense basilar artery sign without evidence of acute infarction or hemorrhage. After treated with aspirin and dipyridamole, he had massive symptomatic brainstem hemorrhagic transformation on the next day. After medical treatment, he survived but remained in locked-in state with occasional drowsiness. CONCLUSION: Hemorrhagic transformation following brainstem infarction is a rare yet potentially devastating condition in patients without thrombolytic therapy. It should be considered when neurological deterioration develops in patients with brainstem infarction. Follow-up brain imaging studies are warranted because antithrombotic agents should be discontinued in case of hemorrhagic transformation. PMID- 27411798 TI - Generalized Convulsion Complicating Acute Diffuse Pulmonary Hemorrhage: The Report of a Rare Case. AB - PURPOSE: The immediate complications associated with a generalized tonic-clonic (GTC) seizure usually involve injuries such as aspiration pneumonia, head injury, skull or vertebral fracture and orolingual biting injury. Here we present a young man who suffered from GTC that was followed by a rare complication, acute diffuse pulmonary hemorrhage, which presented with massive hemoptysis and subsequent respiratory failure. CASE REPORT: An 18-year-old boy developed a GTC convulsion that lasted for about two minutes and then regained consciousness 15 minutes later. Another GTC convulsion occurred four hours later for about two minutes. Upon admission, coughing with blood clots was noted and was initially imputed to a bite wound affecting the tongue. However, massive hemoptysis developed soon after. A chest X-ray showed diffuse consolidation of the bilateral lungs. He was transferred to the intensive care unit and was intubated immediately owing to acute respiratory failure. A further chest CT also showed extensive consolidation of the bilateral lungs, mainly in the central and posterior portions. Bronchoscopy showed diffuse tracheal and bronchial erythematous mucosa and post hemorrhage changes. Laboratory surveys for autoimmune disease, infectious disease, tuberculosis and intoxication gave normal results. After treatment with anticonvulsants, antibiotics and corticosteroids, he was stabilized and extubated on the 5th day of hospitalization. CONCLUSION: The disease entity of acute diffuse pulmonary hemorrhage is similar to neurogenic pulmonary edema. Physicians should be aware of this extremely rare but life-threatening complication, namely seizure-related acute diffuse pulmonary hemorrhage. The patient's response to respiratory support and corticosteroid is usually quite satisfactory. PMID- 27411799 TI - Update of Neurositmulation for Refractory Epilepsy: Deep Brain Stimulation and Responsive Neurostimulation. PMID- 27411800 TI - Erythromelalgia: a Red Neuralgia. PMID- 27411802 TI - Candida vulturna pro tempore sp. nov., a dimorphic yeast species related to the Candida haemulonis species complex isolated from flowers and clinical sample. AB - In a taxonomic study of yeasts isolated from flowers in Cagayan de Oro, Mindenao Island, The Philippines, strains were identified as representing Kabatiella microsticta, Metschnikowia koreensis and a hitherto undescribed dimorphic species. Sequences of the D1/D2 domains of the LSU 26S rRNA genes, the internal transcribed spacer (ITS) regions and the SSU 18S rRNA genes were identical in the strains of the last-named group and differed from the corresponding sequences of the type strain of the closest related species, Candida duobushaemulonii, by 4 % (D1/D2), 7 % (ITS) and 1 % (SSU). In an independent study, a strain with D1/D2 and ITS sequences very similar to those of the Philippine strains was isolated in Malaysia from the blood of a patient dying of aspiration pneumonia. Both groups of isolates were moderately sensitive to anidulafungin, caspofungin, fluconazole, itraconazole and voriconazole but resistant to amphotericin B. Molecular phylogenetic analysis of the sequences placed the Philippine and Malaysian isolates close to the Candida haemulonis complex of Candida species. To reflect the geographical location of the sites of sample collection, the novel species name Candida vulturna pro tempore sp. nov. is proposed to accommodate these strains. The type strain is 11-1170T (=CBS 14366T=CCY 094-001-001T=NCAIM-Y02177T) isolated in Cagayan de Oro, The Philippines. Mycobank: MB 817222. PMID- 27411801 TI - Interplay between the effects of a Protein Kinase C phosphomimic (T204E) and a dilated cardiomyopathy mutation (K211Delta or R206W) in rat cardiac troponin T blunts the magnitude of muscle length-mediated crossbridge recruitment against the beta-myosin heavy chain background. AB - Failing hearts of dilated cardiomyopathy (DCM)-patients reveal systolic dysfunction and upregulation of several Protein Kinase C (PKC) isoforms. Recently, we demonstrated that the functional effects of T204E, a PKC phosphomimic of cardiac troponin T (TnT), were differently modulated by alpha- and beta-myosin heavy chain (MHC) isoforms. Therefore, we hypothesized that the interplay between the effects of T204E and a DCM-linked mutation (K211Delta or R206W) in TnT would modulate contractile parameters linked-to systolic function in an MHC-dependent manner. To test our hypothesis, five TnT variants (wildtype, K211Delta, K211Delta + T204E, R206W, and R206W + T204E) were generated and individually reconstituted into demembranated cardiac muscle fibers from normal (alpha-MHC) and propylthiouracil-treated (beta-MHC) rats. Steady-state and mechano-dynamic measurements were performed on reconstituted fibers. Myofilament Ca(2+) sensitivity (pCa50) was decreased by both K211Delta and R206W to a greater extent in alpha-MHC fibers (~0.15 pCa units) than in beta-MHC fibers (~0.06 pCa units). However, T204E exacerbated the attenuating influence of both mutants on pCa50 only in beta-MHC fibers. Moreover, the magnitude of muscle length (ML) mediated crossbridge (XB) recruitment was decreased by K211Delta + T204E (~47 %), R206W (~34 %), and R206W + T204E (~36 %) only in beta-MHC fibers. In relevance to human hearts, which predominantly express beta-MHC, our data suggest that the interplay between the effects of DCM mutations, PKC phosphomimic in TnT, and beta MHC lead to systolic dysfunction by attenuating pCa50 and the magnitude of ML mediated XB recruitment. PMID- 27411804 TI - Regulation of Rev expression by the equine infectious anaemia virus tat-rev mRNA Kozak sequence and its potential influence on viral replication. AB - Rev, an important accessory protein of equine infectious anaemia virus (EIAV), induces the nuclear export of incompletely spliced viral mRNAs. Rev is translated from the tat-rev mRNA through leaky scanning of the tat CUG. In this study, the function of the Kozak sequence at the beginning of the rev ORF was investigated. Deletion or attenuation of the Kozak sequence resulted in expression of an N terminal 11 aa-truncated Rev in addition to WT Rev. Truncated Rev displayed weaker promotion of Gag expression and processing than WT Rev. Furthermore, EIAV rescued from an infectious molecular clone (pEIAVUK3) with Kozak attenuation exhibited decreased viral replication in host cells in vitro. These results provide a new understanding of the relationship between EIAV Rev expression and viral replication. PMID- 27411803 TI - Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug. AB - Absorption modeling has demonstrated its great value in modern drug product development due to its utility in understanding and predicting in vivo performance. In this case, we integrated physiologically based modeling in the development processes to effectively design extended-release (ER) clinical products for an ester prodrug LY545694. By simulating the trial results of immediate-release products, we delineated complex pharmacokinetics due to prodrug conversion and established an absorption model to describe the clinical observations. This model suggested the prodrug has optimal biopharmaceutical properties to warrant developing an ER product. Subsequently, we incorporated release profiles of prototype ER tablets into the absorption model to simulate the in vivo performance of these products observed in an exploratory trial. The models suggested that the absorption of these ER tablets was lower than the IR products because the extended release from the formulations prevented the drug from taking advantage of the optimal absorption window. Using these models, we formed a strategy to optimize the ER product to minimize the impact of the absorption window limitation. Accurate prediction of the performance of these optimized products by modeling was confirmed in a third clinical trial. PMID- 27411805 TI - Considerations for Systemic Treatment of Psoriasis in Obese Patients. AB - Psoriasis is an immune-mediated inflammatory skin disease frequently associated with metabolic disorders, including diabetes, dyslipidaemia and metabolic syndrome. Moreover, a growing number of studies confirm the association between psoriasis and obesity. It has been found that obesity, as measured by body mass index >30 kg/m2, can double the risk of incident psoriasis. A positive correlation between different measures of adiposity and the severity of psoriasis has also been reported. Epidemiologic studies have also provided robust evidence confirming the association between obesity and psoriatic arthritis. Genetic, metabolic and environmental factors are all likely to contribute to these associations. Adipose tissue is an active endocrine and paracrine organ that has a key role in lipid and glucose metabolism as well as inflammation. Fat tissue is traditionally distributed into two main compartments with different metabolic characteristics, i.e. the subcutaneous and visceral adipose tissue. Particular attention has been devoted to visceral adiposity because of its contribution to inflammation and atherosclerosis. The association between psoriasis and obesity should be properly considered when choosing a systemic treatment, because it could exert negative effects on metabolic parameters, including liver enzymes, serum lipids and renal function. Obesity may increase the risk of liver and renal toxicity from methotrexate and cyclosporine. Moreover, obesity can compromise the effectiveness of systemic treatments for psoriasis (conventional and biological therapies). Dermatologists are also expected to promote a healthy lifestyle and weight loss for obese patients because they could improve metabolic parameters and responsiveness to psoriasis therapies. PMID- 27411806 TI - MRI gray and white matter measures in progressive supranuclear palsy and corticobasal syndrome. AB - We evaluated MRI measures of gray and white matter damages in 19 patients with progressive supranuclear palsy (PSP), 11 with corticobasal syndrome (CBS), and 14 healthy subjects (HS) to differentiate patients with PSP from those with CBS. We calculated surface-based maps of the cortical volume, cortical thickness, surface area, and voxel level maps of sub-cortical volume, and diffusion tensor imaging parameters using automated scripts implemented in FreeSurfer and FSL toolboxes. No significant differences in cortical volume loss were observed between PSP and CBS. When cortical volume was divided into cortical thickness and surface area, cortical thickness in peri-rolandic brain regions was significantly smaller in CBS than in PSP patients, whereas surface area was significantly smaller in PSP than HS. We also found widespread volume loss in sub-cortical structures in patients with PSP and CBS in comparison to HS. Both patient groups displayed diffusion tensor imaging abnormalities: compared to HS, widespread fractional anisotropy and radial diffusivity changes were observed in PSP, whereas axial and radial diffusivity changes were prominent in CBS. Mini-mental state examination positively correlated with diffusion changes in patients with PSP. In conclusion, cortical thickness, surface area, and diffusion tensor imaging parameters may be sensitive enough to help differentiate patients with PSP from those with CBS. PMID- 27411807 TI - Suicidal ideation and attempts in patients with stroke: a population-based study. AB - Stroke is known to be associated with an increase in the risk for suicide. However, there are very few population-based studies investigating the risk of suicidal ideation and attempts in patients with stroke. The purpose of this study was to compare the risk of suicidal ideation and attempts between patients with stroke and population without stroke using nationwide survey data. Individual level data were obtained from 228,735 participants (4560 with stroke and 224,175 without stroke) of the 2013 Korean Community Health Survey. Demographic characteristics, socioeconomic status, physical health status, and mental health status were compared between patients with stroke and population without stroke. Multivariable logistic regression was performed to investigate the independent effects of the stroke on suicidal ideation and attempts. Stroke patients had more depressive mood (12.6 %) than population without stroke (5.7 %, p < 0.001). Stroke patients experienced more suicidal ideation (24.4 %) and attempts (1.3 %) than population without stroke (9.8 and 0.4 %, respectively; both p < 0.001). Stroke was found to increase the risk for suicidal ideation (OR 1.65, 95 % CI 1.52-1.79) and suicidal attempts (OR 1.64, 95 % CI 1.21-2.22), adjusting for demographics, socioeconomic factors, and physical health and mental health factors. We found that stroke increased the risk for suicidal ideation and attempts, independent of other factors that are known to be associated with suicidality, suggesting that stroke per se may be an independent risk factor for suicidality. PMID- 27411808 TI - HLA B27 typing in 511 children with juvenile idiopathic arthritis from India. AB - The enthesitis-related arthritis (ERA) category of juvenile idiopathic arthritis (JIA) is the most common category in India. HLA B27 has a high prevalence in ERA, and ILAR classification includes it in exclusion criteria for other categories, but due to its cost, it is not routinely done. We undertook this study to assess the prevalence of HLA B27 in ERA and other groups of juvenile arthritis in India. Consecutive patients of JIA ERA and select patients from other categories were recruited from a single tertiary care hospital over a span of 3 years. HLA B27 was tested using PCR. Five hundred and eleven children were studied: 312 had ERA, and 199 had other categories (29 oligoarthritis, 107 polyarthritis, 44 systemic onset JIA, 9 psoriatic arthritis and 10 undifferentiated). The prevalence of HLA B27 was highest in the ERA group (87 %) and correlated with the presence of sacroiliitis. Prevalence was 10.3 % in oligoarthritis, 16 % in polyarticular rheumatoid factor (RF)-positive arthritis, 26 % in RF-negative polyarticular arthritis, 66 % in psoriatic arthritis and 40 % in the unclassified and 0 % in systemic onset category. Twenty-seven children had a change in category of JIA as per ILAR owing to HLA B27 testing positive, most commonly in the RF-negative polyarthritis group. Only six of these had clinical features suggestive of Spondyloarthropathy. There is high prevalence of HLA B27 in ERA. Though HLA B27 testing helps in correct classification, a minority of these patients have features suggestive of spondyloarthropathy like back pain, enthesitis or sacroiliitis. PMID- 27411809 TI - High type I error and misrepresentations in search for transgenerational epigenetic inheritance: response to Guerrero-Bosagna. AB - In a recent paper, we described our efforts in search for evidence supporting epigenetic transgenerational inheritance caused by endocrine disrupter chemicals. One aspect of our study was to compare genome-wide DNA methylation changes in the vinclozolin-exposed fetal male germ cells (n = 3) to control samples (n = 3), their counterparts in the next, unexposed, generation (n = 3 + 3) and also in adult spermatozoa (n = 2 + 2) in both generations. We reported finding zero common hits in the intersection of these four comparisons. In our interpretation, this result did not support the notion that DNA methylation provides a mechanism for a vinclozolin-induced transgenerational male infertility phenotype. In response to criticism by Guerrero-Bosagna regarding our statistical power in the above study, here we provide power calculations to clarify the statistical power of our study and to show the validity of our conclusions. We also explain here how our data is misinterpreted in the commentary by Guerrero-Bosagna by leaving out important data points from consideration.Please see related Correspondence article: xxx (13059_2016_982) and related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0619-z. PMID- 27411810 TI - Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer. AB - The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFbeta because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFbeta inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFbeta. Patient specific information was seeded into the HCA model to predict the effect of TGFbeta inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer. PMID- 27411811 TI - The 2014 FDA assessment of commercial fish: practical considerations for improved dietary guidance. AB - The U.S. Food and Drug Administration (FDA) recently released its report: A Quantitative Assessment of the Net Effects on Fetal Neurodevelopment from Eating Commercial Fish (As Measured by IQ and also by Early Age Verbal Development in Children). By evaluating the benefits and potential concerns of eating fish during pregnancy and breastfeeding, the analysis suggests that pregnant women consuming two seafood meals (8-12 oz) per week could provide their child with an additional 3.3 IQ points by age 9. Recent insights from behavioral economics research indicate that other factors, such as concerns about price and methylmercury (MeHg) exposure, appear to reduce fish consumption in many individuals.To assess the net effects of eating commercial fish during pregnancy, we compared the consumption of select fish species necessary to achieve IQ benefits with the amount necessary to have adverse developmental effects due to MeHg exposure. For the species or market types evaluated, the number of servings necessary to reach MeHg exposure to observe an adverse effect was at least twice that the amount estimated to achieve peak developmental benefit. We then reported average costs of fresh and canned or pouched fish, and calculated the cost per week for pregnant women to achieve maximum IQ benefits for their gestating child. Canned light tuna was the least expensive option at $1.83 per week to achieve maximum IQ benefit.Due to their relatively low cost, canned and pouched fish products eaten with enough regularity are likely to provide peak cognitive benefits. Because of its popularity, canned and pouched tuna could provide some of the largest cognitive benefits from fish consumption in the U.S. Future FDA consumer advice and related educational initiatives could benefit from a broader perspective that highlights the importance of affordable and accessible fish choices. These observations underscore the importance of clear public health messaging that address both health benefits and such real-world considerations as cost and convenience. PMID- 27411813 TI - Bacterial selection by mycospheres of Atlantic Rainforest mushrooms. AB - This study focuses on the selection exerted on bacterial communities in the mycospheres of mushrooms collected in the Brazilian Atlantic Rainforest. A total of 24 paired samples (bulk soil vs. mycosphere) were assessed to investigate potential interactions between fungi and bacteria present in fungal mycospheres. Prevalent fungal families were identified as Marasmiaceae and Lepiotaceae (both Basidiomycota) based on ITS partial sequencing. We used culture-independent techniques to analyze bacterial DNA from soil and mycosphere samples. Bacterial communities in the samples were distinguished based on overall bacterial, alphaproteobacterial, and betaproteobacterial PCR-DGGE patterns, which were different in fungi belonging to different taxa. These results were confirmed by pyrosequencing the V4 region of the 16S rRNA gene (based on five bulk soil vs. mycosphere pairs), which revealed the most responsive bacterial families in the different conditions generated beneath the mushrooms, identified as Bradyrhizobiaceae, Burkholderiaceae, and Pseudomonadaceae. The bacterial families Acetobacteraceae, Chrhoniobacteraceae, Planctomycetaceae, Conexibacteraceae, and Burkholderiaceae were found in all mycosphere samples, composing the core mycosphere microbiome. Similarly, some bacterial groups identified as Koribacteriaceae, Acidobacteria (Solibacteriaceae) and an unclassified group of Acidobacteria were preferentially present in the bulk soil samples (found in all of them). In this study we depict the mycosphere effect exerted by mushrooms inhabiting the Brazilian Atlantic Rainforest, and identify the bacteria with highest response to such a specific niche, possibly indicating the role bacteria play in mushroom development and dissemination within this yet-unexplored environment. PMID- 27411812 TI - Imidazoleacetic acid-ribotide in vestibulo-sympathetic pathway neurons. AB - Imidazole-4-acetic acid-ribotide (IAARP) is a putative neurotransmitter/modulator and an endogenous regulator of sympathetic drive, notably systemic blood pressure, through binding to imidazoline receptors. IAARP is present in neurons and processes throughout the CNS, but is particularly prevalent in regions that are involved in blood pressure control. The goal of this study was to determine whether IAARP is present in neurons in the caudal vestibular nuclei that participate in the vestibulo-sympathetic reflex (VSR) pathway. This pathway is important in modulating blood pressure upon changes in head position with regard to gravity, as occurs when humans rise from a supine position and when quadrupeds climb or rear. Sinusoidal galvanic vestibular stimulation was used to activate the VSR and cfos gene expression in VSR pathway neurons of rats. These subjects had previously received a unilateral FluoroGold tracer injection in the rostral or caudal ventrolateral medullary region. The tracer was transported retrogradely and filled vestibular neuronal somata with direct projections to the injected region. Brainstem sections through the caudal vestibular nuclei were immunostained to visualize FluoroGold, cFos protein, IAARP and glutamate immunofluorescence. The results demonstrate that IAARP is present in vestibular neurons of the VSR pathway, where it often co-localizes with intense glutamate immunofluorescence. The co-localization of IAARP and intense glutamate immunofluorescence in VSR neurons may represent an efficient chemoanatomical configuration, allowing the vestibular system to rapidly up- and down-modulate the activity of presympathetic neurons in the ventrolateral medulla, thereby altering blood pressure. PMID- 27411814 TI - Nocardioides gilvus sp. nov., isolated from Namtso Lake. AB - A Gram-stain positive, facultatively anaerobic, non-motile and rod to coccoid shaped bacterium, designated XZ17(T), was isolated from Namtso Lake of Tibet, China. Strain XZ17(T) grew optimally at pH 8.0-9.0, at 30-33 degrees C and in the presence of 0-1.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strain XZ17(T) belongs to the genus Nocardioides in the family Nocardioidaceae. Strain XZ17(T) shared pairwise 16S rRNA gene sequence similarities of 97.2, 96.8, 96.5, 96.4 and <96.0 % to Nocardioides solisilvae KCTC 39528(T), Nocardioides daejeonensis JCM 16922(T), Nocardioides jensenii NCIB 9770(T), Nocardioides dubius KCTC 9992(T) and other Nocardioides species, respectively. It contained MK-8 (H4) as the predominant menaquinone and C17:1 omega8c, C15:0, C17:0 and C18:1 omega9c as the major fatty acid. The strain had cell wall peptidoglycan based on LL-2,6-diaminopimelic acid. The polar lipids of strain XZ17(T) comprised diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids, three unidentified glycolipids and two unidentified lipids. The DNA G+C content of strain XZ17(T) was 68.9 mol%. Based on distinctive phenotypic characteristics, phylogenetic analysis and chemotaxonomic data, it can be concluded that strain XZ17(T) represents a novel species within the genus Nocardioides, for which the name Nocardioides gilvus sp. nov. is proposed. The type strain is strain XZ17(T) (=KCTC 39561(T) = MCCC 1H00114(T)). PMID- 27411815 TI - Association between small dense LDL and sub-clinical atherosclerosis in patients with psoriatic arthritis. AB - Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder occurring in patients with psoriasis. Several studies have shown an association between Psa and traditional atherosclerotic risk factors. We evaluated the relationship between small dense low-density lipoproteins particles (sd-LDL) a risk marker for atherosclerosis, sub-clinical atherosclerosis and PsA in a group of 50 patients with PsA and in 100 controls. Cholesterol, high-density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides, insulin, homeostasis model assessment (HOMA), Apo B, and sd-LDL have been measured. LDL particle separation was performed and seven LDL subfractions were obtained, LDL score (percentage of sd LDL) and mean LDL particle size were calculated. PsA patients and control group differ significantly (p < 0.001) in triglycerides values (119.3 +/- 52.0 vs 90.7 +/- 40.7 mg/dL), Apo B (1.1 +/- 0.2 vs 0.9 +/- 0.1 g/L), insulin (8.9 +/- 4.9 vs 5.8 +/- 3.2 mU/L), HOMA (2.2 +/- 1.7 vs 1.3 +/- 0.8), BMI (27.7 +/- 3.3 vs 25.8 +/- 3.8). LDL score is significantly higher in PsA as compared to control (9.0 +/ 10.7 vs 2.9 +/- 4.7 mg/dL); and mean LDL size is significantly lower in PsA than control (268.1 +/- 4.6 vs 271.2 +/- 2.7 A). These differences were confirmed when stratifying PsA patients for treatment and for disease activity. LDL score and LDL diameter significantly were correlated with the carotid IMT in patients with PsA. These findings show a novel relationship between LDL score and mean LDL size with PsA diagnosis and with sub-clinical atherosclerosis. Sd-LDL gives potentially useful information in the risk assessment for atherosclerotic disease in PsA patients. PMID- 27411817 TI - Effect of early sensory experience on the exploratory activity in adult animals. AB - It was previously found that the exploratory activity of adult Wistar rats with their vibrissae cut in the period from 9 to 20 postnatal days was characterized by lower intragroup variability in comparison with control rats [3]. The present study has shown that the earlier limitation of species-specific afferentation (whisker trimming on postnatal days 2-9) does not induce such changes. We conclude that high plasticity of the brain during the early postnatal period provides better adaptation to the deficit of sensory information. PMID- 27411816 TI - Metformin inhibits development of colon malignant tumors induced by 1,2 dimethylhydrazine in rats. AB - It has been shown that metformin dose-dependently inhibits the development of colon tumors induced by 1,2-dimethylhydrazine (DMH) in rats. The metformin effect manifested itself as a decrease in the amount and average size of tumors, increased degree of their differentiation, and reduction of invasion depth, which was more pronounced in the group of animals that received metformin at a dose of 100 mg/kg of body weight as compared with rats treated with metformin at a dose of 300 mg/kg. PMID- 27411818 TI - Detection of flashing areas attributed to the frog cardiac function in the vagosympathetic trunk placed into a high frequency electric field. AB - In a high frequency electric field, two flashing areas were observed during each contraction of the heart in the vagosympathetic trunk of a paralyzed frog with an intact brain. One area with a higher diameter was moving along the nerve from the heart at a speed of 16.6 +/- 0.2 m/s. It was identified as afferent. Another area with a smaller diameter was spreading along the nerve towards the venous sinus of the frog heart at a speed of 5.6 +/- 0.3 m/s, and it was efferent. PMID- 27411819 TI - Role of additive stochastic modulation of the heart activity in the formation of 0.1-Hz blood flow oscillations in the human cardiovascular system. AB - In the framework of our previous hypothesis about the participation of structural and hydrodynamic properties of the vascular bed in the formation of the 0.1-Hz component of blood flow oscillations in the human cardiovascular system and on the basis of the reduced hydrodynamic model, the role of additive stochastic perturbations of the operation of the single-chamber pump that simulates the heart was investigated. It was shown that aperiodic noise modulation of the rigidity of the walls of the pump or its valves generates low-frequency oscillations of pressure and blood flow velocity of arterial vascular bed with the maximum amplitude at a frequency close to 0.1 Hz. PMID- 27411820 TI - Semax prevents learning and memory inhibition by heavy metals. AB - Separate and joint effect of Semax, ascorbic acid, lead diacetate, and ammonium molybdate on avoidance conditioning in rats was studied. It was established that the heavy metal salts inhibited the avoidance response, and the peptide counteracted this inhibition as strongly as ascorbic acid or to a comparable degree. These findings confirm the antioxidant properties of Semax. PMID- 27411821 TI - Presynaptic nicotinic cholinoreceptors modulate velocity of the action potential propagation along the motor nerve endings at a high-frequency synaptic activity. AB - Experiments on frog neuromuscular junctions have demonstrated that asynchrony of the acetylcholine quantal release forming the multi-quantal evoked response at high-frequency synaptic activity is caused, in particular, by a decrease in velocity of the action potential propagation along the non-myelinated nerve endings, which is mediated by activation of the alpha7 and alpha4beta4 nicotinic cholinoreceptors. PMID- 27411823 TI - Fine morphology of frontal filaments in nauplii of cirriped crustaceans. AB - Fine morphology of the frontal filaments (FFs) at all nauplius stages of two barnacle species (Verruca stroemia and Hesperibalanus hesperius) has been investigated by scanning electron microscopy. FFs have been detected at the second nauplius stage and persist during all stages. FFs contain a wide proximal and a fine distal parts, but they are not actually separated as segments of the limbs, and the area between them looks like a single cuticular crease. Apical and subapical pores have been found at the top of each FF in the larvae of both species, which may indicate the chemoreceptor function of these organs. PMID- 27411822 TI - Morphological diversity of mole vole mono- and polymorphic populations: Does Chernov's "compensation principle" work within a population? AB - The ecological "compensation principle" enunciated by Yu.I. Chernov, who suggested a higher level of compensatory diversity in communities depleted in composition, proved to be also applicable to a single population, as demonstrated in a model rodent species, mole vole with mono- and polymorphic coat color, using the methods of geometric morphometrics. The mandible shape diversity was significantly increased in the monomorphic as compared to polymorphic populations, in which the division of foraging activities between animals of different morphs led to a suppression of general morphological diversity. PMID- 27411824 TI - The ultrastructure of the zoospores of the parasitic dinoflagellate Ichthyodinium chabelardi Hollande et J. Cachon, 1952 (Alveolata: Dinoflagellata). AB - This is the first study on the ultrastructure of the zoospores of Ichthyodinium chabelardi, a parasitoid of the fish egg and early larval stages. The zoospores were characterized by the cell structure specific for dinoflagellates; particularly, cells contained large trichocysts and the "dinokaryon"-type nucleus. An unusual large electron-transparent zone was the only significant difference from the "classical" cell structure in Dinoflagellata. We did not find cell structures for the penetration to the host cell (microtubular basket, conoid, or secretory organelles such as rhoptries). The data on the fine structure of the zoospores of I. chabelardi agree with the results of molecular phylogeny; this allows us argue that excluding this species from Dinoflagellata and assigning it to Protalveolata was a mistake. PMID- 27411825 TI - Ultrastructural evidence of the excretory function in the asteroid axial organ (Asteroidea, Echinodermata). AB - The ultrastructure of the axial organ of Asterias amurensis has been studied The organ is a network of canals of the axial coelom separated by haemocoelic spaces. The axial coelom is lined with two types of monociliary cells: podocytes and musculo-epithelial cells. Podocytes form numerous basal processes adjacent to the basal lamina on the coelomic side. Musculo-epithelial cells form processes running along the basal lamina. Some bundles of these processes wrapped in the basal lamina pass through haemocoelic spaces between neighboring coelomic canals. It is hypothesized that the axial organ serves for filtration of fluid from haemocoelic spaces into the axial coelom cavity, from which urine is excreted through the madreporite to the exterior. PMID- 27411826 TI - Age-dependent accumulation of (137)Cs by pike Esox lucius in the Yenisei River. AB - Age-dependent accumulation of (137)Cs in the muscles and bodies of the pike Esox lucius (aged two to seven years) inhabiting a section of the Yenisei River polluted with artificial radionuclides has been studied. The content of (137)Cs in muscles varied from 0.5 to 7.0 Bq/kg of fresh weight. The maximum content of the radionuclide has been found in juveniles. The content of (137)Cs in pike muscles and body decreased considerably with age. The high content of (137)Cs in the muscles of juveniles is probably a consequence of their higher intensity of feeding as compared to older individuals, which is due to the intense growth of juveniles. PMID- 27411827 TI - Extreme negative temperatures and body mass loss in the Siberian salamander (Salamandrella keyserlingii, amphibia, hynobiidae). AB - Frozen Siberian salamander safely tolerates long (45 days) stay at-35 degrees C. Short-term (3 days) cooling down to-50 degrees C was tolerable for 40% of adult individuals; down to-55 degrees C, for 80% of the underyearlings. Generally, the salamanders lose about 28% of the body mass during the pre-hibernating period (before winter, at temperatures as low as 0 degrees C) and during the process of freezing (as low as-5 degrees C). The body weight remained constant upon further cooling (to-35 degrees C). The frozen salamanders have no physiological mechanisms protecting from sublimation. PMID- 27411828 TI - The biotic balance in Lake Baikal: Comparison of the results of modeling and observations. AB - A mass-balance model has been applied to estimation of the biotic energy flow through the ecosystem of Lake Baikal. The prediction of the annual production of primary producers, reducers, and consumers (including fish) has been made based on the model. PMID- 27411829 TI - Dynamics of testosterone concentration in male steppe lemmings (Lagurus lagurus) in the reproductive cycle reflects the species-specific mating system. AB - In the blood of male steppe lemmings, relatively low background levels of testosterone were detected, this is characteristic of a monogamous species. A significant increase in testosterone level, more expressed in sexually active males, was observed at the initial stage of formation of reproductive couples. Apparently, in the future, the couple will exist in a stable relationship, and, hence, the maintenance of a high testosterone level becomes excessive. The decrease in, and the relative "normalization" of, the hormone level during the existence of the pair, including raising of the young, promotes higher expression of the male paternal care of the offspring at the species level. PMID- 27411830 TI - Controlling Spatial Heat and Light Distribution by Using Photothermal Enhancing Auto-Regulated Liposomes (PEARLs). AB - Photothermal therapy (PTT) is enhanced by the use of nanoparticles with a large optical absorption at the treatment wavelength. However, this comes at the cost of higher light attenuation that results in reduced depth of heating as well as larger thermal gradients, leading to potential over- and under-treatment in the target tissue. These limitations can be overcome by using photothermal enhancing auto-regulating liposomes (PEARLs), based on thermochromic J-aggregate forming dye-lipid conjugates that reversibly alter their absorption above a predefined lipid phase-transition temperature. Under irradiation by near-infrared light, deeper layers of the target tissue revert to the intrinsic optical absorption, halting the temperature rise and enabling greater light penetration and heat generation at depth. This effect is demonstrated in both nanoparticle solutions and in gel phantoms containing the nanoparticles. PMID- 27411831 TI - GP0.4 from bacteriophage T7: in silico characterisation of its structure and interaction with E. coli FtsZ. AB - BACKGROUND: Proteins produced by bacteriophages can have potent antimicrobial activity. The study of phage-host interactions can therefore inform small molecule drug discovery by revealing and characterising new drug targets. Here we characterise in silico the predicted interaction of gene protein 0.4 (GP0.4) from the Escherichia coli (E. coli) phage T7 with E. coli filamenting temperature sensitive mutant Z division protein (FtsZ). FtsZ is a tubulin homolog which plays a key role in bacterial cell division and that has been proposed as a drug target. RESULTS: Using ab initio, fragment assembly structure modelling, we predicted the structure of GP0.4 with two programs. A structure similarity-based network was used to identify a U-shaped helix-turn-helix candidate fold as being favoured. ClusPro was used to dock this structure prediction to a homology model of E. coli FtsZ resulting in a favourable predicted interaction mode. Alternative docking methods supported the proposed mode which offered an immediate explanation for the anti-filamenting activity of GP0.4. Importantly, further strong support derived from a previously characterised insertion mutation, known to abolish GP0.4 activity, that is positioned in close proximity to the proposed GP0.4/FtsZ interface. CONCLUSIONS: The mode of interaction predicted by bioinformatics techniques strongly suggests a mechanism through which GP0.4 inhibits FtsZ and further establishes the latter's druggable intrafilament interface as a potential drug target. PMID- 27411833 TI - The Emerging Role of Regucalcin as a Tumor Suppressor: Facts and Views. AB - Regucalcin (RGN) is a multifunctional protein that was first described as a calcium (Ca2+)-binding protein playing a relevant role in the maintenance of intracellular Ca2+ concentration. However, due to its downregulated expression with aging, RGN is also known as senescence marker protein-30. The RGN protein is an X-chromosome gene product, whose transcription is regulated by a myriad of hormonal and non-hormonal factors. Besides the well-known role in Ca2+ homeostasis, RGN has also been linked to the control of several intracellular signaling pathways, and basic biological processes, such as oxidative stress, cell proliferation, apoptosis, and metabolism. RGN has been shown to have antioxidant properties by its activity reducing the production of reactive oxygen species and increasing the antioxidant defenses. The role of RGN suppressing cell proliferation is associated with the regulation of expression of oncogenes and tumor suppressor genes. It results clear that all the existent knowledge implicates RGN in the control of the main biological processes actually recognized as the hallmarks of cancer. Moreover, it has been shown that tumor onset and progression are underpinned by the loss of RGN expression, whereas RGN overexpression showed to have a protective role against the development of chemicallyinduced tumors. This review describes the mechanisms that control the tissue expression of RGN and discusses the experimental evidence that indicate RGN as a new tumor suppressor protein. PMID- 27411832 TI - Establishing stereotactic body radiotherapy with flattening filter free techniques in the treatment of pulmonary lesions - initial experiences from a single institution. AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) using flattening filter free (FFF)-techniques has been increasingly applied during the last years. However, clinical studies investigating this emerging technique are still rare. Hence, we analyzed toxicity and clinical outcome of pulmonary SBRT with FFF-techniques and performed dosimetric comparison to conventional techniques using flattening filters (FF). MATERIALS AND METHODS: Between 05/2014 and 06/2015, 56 consecutive patients with 61 pulmonary lesions were treated with SBRT in FFF-mode. Central lesions received 8 * 7.5 Gy delivered to the conformally enclosing 80 %-isodose, while peripheral lesions were treated with 3 * 15 Gy, prescribed to the 65 % isodose. Early and late toxicity (after 6 months) as well as initial clinical outcomes were evaluated. Furthermore, [deleted] plan quality and efficiency were evaluated by analyzing conformity, beam- on and total treatment delivery times in comparison to plans with FF-dose application. RESULTS: Median follow-up time was 9.3 months (range 1.5-18.0 months). Early toxicity was low with only 5 patients (8.9 %) reporting CTCAE 2 degrees or higher side-effects. Only one patient (1.8 %) was diagnosed with radiation-induced pneumonitis CTCAE 3 degrees , while 2 (3.6 %) patients suffered from pneumonitis CTCAE 2 degrees . After 6 months, no toxicity greater than CTCAE 2 degrees was reported. 1-year local progression free survival, distant progression-free survival and overall survival were 92.8 %, 78.0 %, and 94.4 %, respectively. While plan quality was similar for FFF- and FF-plans in respect to conformity (p = 0.275), median beam-on time as well as total treatment time were significantly reduced for SBRT in FFF-mode compared to FF-mode (p <= 0.001, p <= 0.001). CONCLUSIONS: Patient treatment with SBRT using FFF-techniques is safe and provides promising clinical results with only modest toxicity at significantly increased dose delivery speed. PMID- 27411834 TI - Effect of maternal Helicobacter Pylori infection on birth weight in an urban community in Uganda. AB - BACKGROUND: Helicobacter pylori, a widespread infection particularly in developing countries has been associated with many adverse effects during pregnancy including hyperemesis gravidarum, neural tube defects in newborns, intrauterine fetal growth restriction and miscarriage. We sought to document the effects of H. pylori infection on birth weight in a low-income setting in Kampala, Uganda. METHODS: This was a prospective cohort study conducted in Kampala between May 2012 and May 2013. The participants were H. pylori positive and H. pylori negative HIV negative primigravidae and secundigravidae. Recruitment was at <=18 gestation weeks and follow up assessments were carried out at 26 and 36 gestation weeks and soon after delivery. H. pylori infection was determined using H. pylori stool antigen test. Maternal weight and height were measured, and body mass index (BMI) and gestational weight gain were calculated. Only term and live babies were considered. Low birth weight (LBW) was defined as a birth weight of <2500 gram. RESULTS: A total of 221 participants were enrolled with mean +/- standard deviation (SD) age of 20.9 +/- 2.7 years. The mean +/- SD gestation age at delivery was 39.4 +/- 1.0 weeks. Primigravidae were 61.5 % (n = 188) and 52.9 % (n = 117) of the participants were positive for H. pylori infection. Low pre-pregnancy BMI (<18.5 kg/m(2)) was recorded in 14.6 % (n = 28) while 38 % (n = 73) had a height <156 cm at recruitment. Of the infants born to the participants, 13.6 % (n = 26) had low birth weight (<2500 gram). Independent predictors for LBW were the mother being positive for H. pylori infection (odds ratio, OR, 3.6, 95 % CI 1.1 - 11.5; P = 0.031) maternal height at recruitment <156 cm (OR 3.4, 95 % CI 1.4-8.2; P = 0.008) and maternal weight gain rates <0.3 kg/week during the 2(nd) and 3(rd) trimesters (OR 3.8, 95 % CI 1.0-14.1; P = 0.044). CONCLUSION: H. pylori infection is associated with LBW among primigravidae and secundigravidae in Kampala, Uganda. PMID- 27411835 TI - Resident duty hour modification affects perceptions in medical education, general wellness, and ability to provide patient care. AB - BACKGROUND: Resident duty hours have recently been under criticism, with concerns for resident and patient well-being. Historically, call shifts have been long, and some residency training programs have now restricted shift lengths. Data and opinions about the effects of such restrictions are conflicting. The Internal Medicine Residency Program at Dalhousie University recently moved from a traditional call structure to a day float/night float system. This study evaluated how this change in duty hours affected resident perceptions in several key domains. METHODS: Senior residents from an internal medicine training program in Canada responded to an anonymous online survey immediately before and 6 months after the implementation of duty hour reform. The survey contained questions relating to three major domains: resident wellness, ability to deliver quality health care, and medical education experience. Mean pre- and post-intervention scores were compared using the t-test for paired samples. RESULTS: Twenty-three of 27 (85 %) senior residents completed both pre- and post-reform surveys. Residents perceived significant changes in many domains with duty hour reform. These included improved general wellness, less exposure to personal harm, fewer feelings of isolation, less potential for error, improvement in clinical skills expertise, increased work efficiency, more successful teaching, increased proficiency in medical skills, more successful learning, and fewer rotation disruptions. CONCLUSIONS: Senior residents in a Canadian internal medicine training program perceived significant benefits in medical education experience, ability to deliver healthcare, and resident wellness after implementation of duty hour reform. PMID- 27411836 TI - Grosvenor Charles Thomas Burfitt-Williams. PMID- 27411837 TI - Cost-effectiveness of implantable cardiac devices in patients with systolic heart failure. AB - OBJECTIVE: To evaluate the cost-effectiveness of implantable cardioverter defibrillators (ICDs), cardiac resynchronisation therapy pacemakers (CRT-Ps) and combination therapy (CRT-D) in patients with heart failure with reduced ejection fraction based on a range of clinical characteristics. METHODS: Individual patient data from 13 randomised trials were used to inform a decision analytical model. A series of regression equations were used to predict baseline all-cause mortality, hospitalisation rates and health-related quality of life and device related treatment effects. Clinical variables used in these equations were age, QRS duration, New York Heart Association (NYHA) class, ischaemic aetiology and left bundle branch block (LBBB). A UK National Health Service perspective and a lifetime time horizon were used. Benefits were expressed as quality-adjusted life years (QALYs). Results were reported for 24 subgroups based on LBBB status, QRS duration and NYHA class. RESULTS: At a threshold of L30 000 per QALY gained, CRT D was cost-effective in 10 of the 24 subgroups including all LBBB morphology patients with NYHA I/II/III. ICD is cost-effective for all non-NYHA IV patients with QRS duration <120 ms and for NYHA I/II non-LBBB morphology patients with QRS duration between 120 ms and 149 ms. CRT-P was also cost-effective in all NYHA III/IV patients with QRS duration >120 ms. Device therapy is cost-effective in most patient groups with LBBB at a threshold of L20 000 per QALY gained. Results were robust to altering key model parameters. CONCLUSIONS: At a threshold of L30 000 per QALY gained, CRT-D is cost-effective in a far wider group than previously recommended in the UK. In some subgroups ICD and CRT-P remain the cost-effective choice. PMID- 27411838 TI - Impact of call-to-balloon time on 30-day mortality in contemporary practice. AB - OBJECTIVE: Studies reporting an association between treatment delay and outcome for patients with ST segment elevation myocardial infarction (STEMI) have generally not included patients treated by a primary percutaneous coronary intervention (PPCI) service that systematically delivers reperfusion therapy to all eligible patients. We set out to determine the association of call-to-balloon (CTB) time with 30-day mortality after PPCI in a contemporary series of patients treated within a national reperfusion service. METHODS: We analysed data on 16 907 consecutive patients with STEMI treated by PPCI in England and Wales in 2011 with CTB time of <=6 hours. RESULTS: The median CTB and door-to-balloon times were 111 and 41 min, respectively, with 80.9% of patients treated within 150 min of the call for help. An out-of-hours call time (58.2% of patients) was associated with a 10 min increase in CTB time, whereas inter-hospital transfer for PPCI (18.5% of patients) was associated with a 49 min increase in CTB time. CTB time was independently associated with 30-day mortality (p<0.0001) with a HR of 1.95 (95% CI 1.54 to 2.47) for a CTB time of >180-240 min compared with <=90 min. The relationship between CTB time and 30-day mortality was influenced by patient risk profile with a greater absolute impact of increasing CTB time on mortality in high-risk patients. CONCLUSION: CTB time is a useful metric to assess the overall performance of a PPCI service. Delays to reperfusion remain important even in the era of organised national PPCI services with rapid treatment times and efforts should continue to minimise treatment delays. PMID- 27411839 TI - Primary percutaneous coronary intervention for ST elevation myocardial infarction in nonagenarians. AB - OBJECTIVE: To assess outcomes following primary percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI) in nonagenarian patients. METHODS: We conducted a multicentre retrospective study between 2006 and 2013 in five international high-volume centres and included consecutive all-comer nonagenarians treated with primary PCI for STEMI. There were no exclusion criteria. We enrolled 145 patients and collected demographic, clinical and procedural data. Severe clinical events and mortality at 6 months and 1 year were assessed. RESULTS: Cardiogenic shock was present at admission in 21%. Median (IQR) delay between symptom onset and balloon was 3.7 (2.4-5.6) hours and 60% of procedures were performed through the transradial approach. Successful revascularisation of the culprit vessel was obtained in 86% of the cases (thrombolysis in myocardial infarction flow of 2 or 3). Major or clinically relevant bleeding was observed in 4% of patients. Median left ventricular ejection fraction post PCI was 41.5% (32.0-50.0). The in-hospital mortality was 24%, with 6 months and 1-year survival rates of 61% and 53%, respectively. CONCLUSIONS: In our study, primary PCI in nonagenarians with STEMI was achieved and feasible through a transradial approach. It is associated with a high rate of reperfusion of the infarct-related artery and 53% survival at 1 year. These results suggest that primary PCI may be offered in selected nonagenarians with acute myocardial infarction. PMID- 27411840 TI - Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults. AB - OBJECTIVE: Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. METHODS: We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A2 (LpPLA2) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression. RESULTS: Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA2 mass, 1.036 (1.006 to 1.066) and LpPLA2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC. CONCLUSION: This study shows novel associations of circulating FGF-23 and fetuin A with MAC, and LpPLA2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC. PMID- 27411841 TI - An unusual finding in a 57-year-old woman with new onset hypertension and a diastolic murmur. AB - CLINICAL INTRODUCTION: A 57-year-old woman presented to our clinic with breathlessness brought on while walking uphill. She had been recently diagnosed with systemic hypertension. There was no known family history of cardiac disease, or prior smoking habit. On examination, pulse was 73 bpm and blood pressure 155/73 mm Hg, which was asymmetrical in her arms. Auscultation revealed a readily audible early diastolic murmur in the aortic area and bilateral subclavian bruits. ECG showed sinus rhythm with no abnormality. Transthoracic echocardiography demonstrated mild-to-moderate aortic regurgitation, and normal left ventricular size and function. The ascending aorta was mildly dilated (41 mm), with para-aortic thickening noted. Owing to the abnormal appearance of the aortic wall, cardiac MRI, and subsequently 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan was performed (figure 1). QUESTION: Which complication of the underlying disease is evident in figure 1, panel C? Aortic aneurysmAortic dissectionAortic thrombusCoronary artery aneurysmCoronary sinus fistula. PMID- 27411842 TI - A nationwide evaluation of spontaneous coronary artery dissection in pregnancy and the puerperium. AB - OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is a rare and potentially lethal cause of myocardial infarction (MI). The purpose of our study was to estimate the prevalence and maternal outcomes of pregnancies complicated by SCAD. MATERIALS AND METHODS: A population-based cohort study on all births identified in the Healthcare Cost and Utilization Project from 2008 to 2012. Disease prevalence was calculated and logistic regression was used to estimate the adjusted odds ratio (aOR) for risk factors and different maternal complications. RESULTS: A total of 4 363 343 pregnancy-related discharges were evaluated. 79 cases of SCAD were identified resulting in a prevalence of 1.81 per 100 000 pregnancies. The mean maternal age at the time of diagnosis was 33.4 years (+/-5.2). Chronic hypertension (aOR, 2.67; 95% CI 1.18 to 6.03), lipid profile abnormalities (aOR, 48.22; 95% CI 24.25 to 95.90), chronic depression (aOR, 3.56; 95% CI 1.43 to 8.83) and history of migraine (aOR, 3.93; 95% CI 1.52 to 10.17) were associated with an elevated risk for SCAD. MI was diagnosed in 66 (85.5%) cases of SCAD with anterior and subendocardial territories being the most common locations. Thirty one patients (40%) with SCAD underwent angioplasty with the majority receiving stents, which was associated with a longer hospital stay than those treated conservatively or with bypass. CONCLUSIONS: SCAD is a rare aetiology of MI; risk factors and outcomes are illustrated in the current study. The puerperium is an important period for the development of pregnancy-related SCAD. Careful evaluation of pregnant and postpartum women with chest pain is warranted, especially if these risk factors are identified. PMID- 27411843 TI - Discovery and in Vivo Evaluation of the Potent and Selective PI3Kdelta Inhibitors 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2 pyridinyl)-4-quinolinecarboxamide (AM-0687) and 2-((1S)-1-((6-Amino-5-cyano-4 pyrimidinyl)amino)ethyl)-5-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-1430). AB - Optimization of the potency and pharmacokinetic profile of 2,3,4-trisubstituted quinoline, 4, led to the discovery of two potent, selective, and orally bioavailable PI3Kdelta inhibitors, 6a (AM-0687) and 7 (AM-1430). On the basis of their improved profile, these analogs were selected for in vivo pharmacodynamic (PD) and efficacy experiments in animal models of inflammation. The in vivo PD studies, which were carried out in a mouse pAKT inhibition animal model, confirmed the observed potency of 6a and 7 in biochemical and cellular assays. Efficacy experiments in a keyhole limpet hemocyanin model in rats demonstrated that administration of either 6a or 7 resulted in a strong dose-dependent reduction of IgG and IgM specific antibodies. The excellent in vitro and in vivo profiles of these analogs make them suitable for further development. PMID- 27411844 TI - Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors. AB - SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase that monomethylates lysine 20 of histone H4 (H4K20) in vivo. The methyltransferase activity of SETD8 has been implicated in many essential cellular processes, including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. In addition to H4K20, SETD8 monomethylates non-histone substrates including proliferating cell nuclear antigen and p53. During the past decade, different structural classes of inhibitors targeting various lysine methyltransferases have been designed and developed. However, the development of SETD8 inhibitors is still in its infancy. This review covers the progress made to date in inhibiting the activity of SETD8 by small molecules, with an emphasis on their discovery, selectivity over other methyltransferases, and cellular activity. PMID- 27411845 TI - Cobalt nanoparticle-embedded carbon nanotube/porous carbon hybrid derived from MOF-encapsulated Co3O4 for oxygen electrocatalysis. AB - We successfully obtained a novel bi-functional electrocatalyst towards the ORR and OER: Co nanoparticle-embedded N-doped carbon nanotube (CNT)/porous carbon (PC) by pyrolyzing metal organic framework (MOF) encapsulated Co3O4. The as obtained hybrid exhibited highly efficient electrocatalytic activity for the ORR and OER. Furthermore, the assembled Zn-air batteries also revealed promising performance and long-term stability. PMID- 27411846 TI - Zika Virus. AB - Zika virus (ZIKV) infections are the latest global public health emergency. Occupational health nurses can protect society by educating workers, women of childbearing age, and others traveling in ZIKV-infected areas about prevention strategies. PMID- 27411847 TI - Estimating causal contrasts involving intermediate variables in the presence of selection bias. AB - An important goal across the biomedical and social sciences is the quantification of the role of intermediate factors in explaining how an exposure exerts an effect on an outcome. Selection bias has the potential to severely undermine the validity of inferences on direct and indirect causal effects in observational as well as in randomized studies. The phenomenon of selection may arise through several mechanisms, and we here focus on instances of missing data. We study the sign and magnitude of selection bias in the estimates of direct and indirect effects when data on any of the factors involved in the analysis is either missing at random or not missing at random. Under some simplifying assumptions, the bias formulae can lead to nonparametric sensitivity analyses. These sensitivity analyses can be applied to causal effects on the risk difference and risk-ratio scales irrespectively of the estimation approach employed. To incorporate parametric assumptions, we also develop a sensitivity analysis for selection bias in mediation analysis in the spirit of the expectation maximization algorithm. The approaches are applied to data from a health disparities study investigating the role of stage at diagnosis on racial disparities in colorectal cancer survival. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27411848 TI - Re: "a new time-series methodology for estimating relationships between elderly frailty, remaining life expectancy, and ambient air quality". PMID- 27411849 TI - Tunable hygromorphism: structural implications of low molecular weight gels and electrospun nanofibers in bilayer composites. AB - This investigation highlights the potential for electrospun nanofiber mats and self-assembled nanofiber networks to be interfaced synergistically to induce hygromorphic behaviour. Control poly(vinyl alcohol) (PVA) electrospun active layers and 1,3:2,4-di-p-methylbenyliedene sorbitol (MDBS) self-assembled passive layers encapsulated in an ethylene oxide-epichlorohydrin (EO-EPI) copolymer matrix were fabricated to examine the influence of composition on the properties guiding hygromorphism, such as water transport, layer thickness, and layer modulus. Experimentally determined material constants were utilized in conjunction with mathematical modeling to determine ideal layer properties. It was revealed that the active layer with the highest PVA content exhibited the fastest water transport, and the passive layer with the highest MDBS content displayed the slowest water transport. However, the hygromorphic bilayer fabricated utilizing the lowest PVA content and the highest MDBS fraction was predicted to induce the highest change in curvature due to the lower modulus and thickness of the PVA nanofiber active layer. Decreasing the MDBS content reduced the passive layer modulus while increasing water transport, which theoretically reduced the overall bilayer curvature. The hygromorphic bilayer composites fabricated using these ideal control layers exhibited folding bias and response variations dependent upon active layer composition and imposed folding directions. By utilizing the favorable force balances between the active layer with the lower PVA content and the passive layer with the highest MDBS amount in conjunction with folding bias in a non-preferential direction, it was possible to achieve hygromorphic unfolding and refolding with hydration. Through modelling and individual layer examination, a unique platform built on two independent fiber networks has been designed to achieve biomimetic hygromorphism in synthetic bilayer composites. PMID- 27411850 TI - Fibroblast Growth Factor Ligand Dependent Proliferation and Chondrogenic Differentiation of Synovium-Derived Stem Cells and Concomitant Adaptation of Wnt/Mitogen-Activated Protein Kinase Signals. AB - Cell expansion techniques commonly utilize exogenous factors to increase cell proliferation and create a larger cell population for use in cell-based therapies. One strategy for cartilage regenerative therapies is autologous stem cell expansion and fibroblast growth factor (FGF) supplementation during cell expansion, particularly FGF-2. However, it is unknown whether FGF-10, another FGF implicated in limb and skeletal development, can elicit the same rejuvenation responses in terms of proliferation and differentiation of human synovium-derived stem cells (SDSCs). In this study, we expanded SDSCs in either FGF-2 or FGF-10 for 7 days; a control group had no treatment. FGF-2 and FGF-10 supplementation was also exclusively tested during the differentiation phase. Expanded SDSCs were evaluated for their ability to successfully engage in chondrogenic and osteogenic differentiation. We found that FGF-2 supplementation during proliferation, but not differentiation, was able to increase glycosaminoglycan deposition, pellet size, and chondrogenic gene expression following chondrogenic induction, as well as increased calcium deposition, alkaline phosphatase activity, and expression of vital osteogenic differentiation genes following osteogenic induction. FGF-10 did not elicit a similar preconditioning effect. We also observed changes of both Wnt signals and mitogen-activated protein kinase expression during SDSC chondrogenesis, which occurred in a manner dependent upon the supplementation phase of FGF-2 administration. These results indicated that FGF-2, but not FGF 10, may be supplemented during stem cell expansion to prime cells for successful chondrogenesis and osteogenesis. PMID- 27411851 TI - TRPC5 channels participate in pressure-sensing in aortic baroreceptors. AB - Blood pressure is maintained within a normal physiological range by a sophisticated regulatory mechanism. Baroreceptors serve as a frontline sensor to detect the change in blood pressure. Nerve signals are then sent to the cardiovascular control centre in the brain in order to stimulate baroreflex responses. Here, we identify TRPC5 channels as a mechanical sensor in aortic baroreceptors. In Trpc5 knockout mice, the pressure-induced action potential firings in the afferent nerve and the baroreflex-mediated heart rate reduction are attenuated. Telemetric measurements of blood pressure demonstrate that Trpc5 knockout mice display severe daily blood pressure fluctuation. Our results suggest that TRPC5 channels represent a key pressure transducer in the baroreceptors and play an important role in maintaining blood pressure stability. Because baroreceptor dysfunction contributes to a variety of cardiovascular diseases including hypertension, heart failure and myocardial infarction, our findings may have important future clinical implications. PMID- 27411852 TI - Ultra-small lipid-polymer hybrid nanoparticles for tumor-penetrating drug delivery. AB - Lipid-polymer hybrid nanoparticles, consisting of a polymeric core coated by a layer of lipids, are a class of highly scalable, biodegradable nanocarriers that have shown great promise in drug delivery applications. Here, we demonstrate the facile synthesis of ultra-small, sub-25 nm lipid-polymer hybrid nanoparticles using an adapted nanoprecipitation approach and explore their utility for targeted delivery of a model chemotherapeutic. The fabrication process is first optimized to produce a monodisperse population of particles that are stable under physiological conditions. It is shown that these ultra-small hybrid nanoparticles can be functionalized with a targeting ligand on the surface and loaded with drug inside the polymeric matrix. Further, the in vivo fate of the nanoparticles after intravenous injection is characterized by examining the blood circulation and biodistribution. In a final proof-of-concept study, targeted ultra-small hybrid nanoparticles loaded with the cancer drug docetaxel are used to treat a mouse tumor model and demonstrate improved efficacy compared to a clinically available formulation of the drug. The ability to synthesize a significantly smaller version of the established lipid-polymer hybrid platform can ultimately enhance its applicability across a wider range of applications. PMID- 27411853 TI - Quantum steering of Gaussian states via non-Gaussian measurements. AB - Quantum steering-a strong correlation to be verified even when one party or its measuring device is fully untrusted-not only provides a profound insight into quantum physics but also offers a crucial basis for practical applications. For continuous-variable (CV) systems, Gaussian states among others have been extensively studied, however, mostly confined to Gaussian measurements. While the fulfilment of Gaussian criterion is sufficient to detect CV steering, whether it is also necessary for Gaussian states is a question of fundamental importance in many contexts. This critically questions the validity of characterizations established only under Gaussian measurements like the quantification of steering and the monogamy relations. Here, we introduce a formalism based on local uncertainty relations of non-Gaussian measurements, which is shown to manifest quantum steering of some Gaussian states that Gaussian criterion fails to detect. To this aim, we look into Gaussian states of practical relevance, i.e. two-mode squeezed states under a lossy and an amplifying Gaussian channel. Our finding significantly modifies the characteristics of Gaussian-state steering so far established such as monogamy relations and one-way steering under Gaussian measurements, thus opening a new direction for critical studies beyond Gaussian regime. PMID- 27411854 TI - Two-stage association study to identify the genetic susceptibility of a novel common variant of rs2075290 in ZPR1 to type 2 diabetes. AB - The SNP of rs964184 in ZPR1 has recently been associated with type 2 diabetes mellitus (T2DM) in Japanese individuals. To comprehensively investigate the association of common variants in ZPR1 with T2DM in Han Chinese individuals, we designed a two-stage case-control study of 3,505 T2DM patients and 6,911 unrelated healthy Han Chinese individuals. A total of 24 single nucleotide polymorphisms (SNPs) were genotyped, and single-SNP association, imputation and gender-specific association analyses were performed. To increase the coverage of genetic markers, we implemented imputation techniques to extend the number of tested makers to 280. A novel SNP, rs2075290, and the previously reported SNP, rs964184, were significantly associated with T2DM in the two independent datasets, and individuals harboring the CC genotype of rs2075290 and GG genotype of rs964184 exhibited higher levels of fasting plasma glucose (FPG) and blood hemoglobin A1c (HbA1c) than individuals of other genotypes. Additionally, haplotype analyses indicated that two haplotype blocks containing rs2075290 or rs964184 were also significantly associated with T2DM. In summary, these results suggest that ZPR1 plays an important role in the etiology of T2DM, and this gene might be involved in abnormal glucose metabolism. PMID- 27411855 TI - Food taboos and nutrition-related pregnancy concerns among Ethiopian women. AB - AIMS AND OBJECTIVES: To discuss Ethiopian food taboos during pregnancy and their relation to maternal nutritional status and pregnancy outcomes. BACKGROUND: Recent waves of migration have seen large groups of Ethiopian refugees moving to countries around the globe. This is of concern as Ethiopian women are at risk of a number of medical and pregnancy complications. Health is further compromised by poor diet and adherence to cultural food beliefs and taboos. In refugee women, many of these factors correspond with significantly higher rates of pregnancy complications and poor birth outcomes. DESIGN: This is a discussion paper informed by a literature review. METHODS: A search of the Scopus, PubMed, Web of Science and Academic Search Premier databases for the keywords Ethiopian, pregnancy, food and taboos was conducted in the research literature published from 1998-2015. This time is contingent with Ethiopian migration trends. RESULTS: Ethiopian migrant women are at risk of inadequate nutrition during pregnancy. Risks include cultural factors associated with food taboos as well as issues associated with low socioeconomic status. Consequently, Ethiopian women are more likely to have nutritional deficiencies such as anaemia which have been associated with a range of pregnancy complications. CONCLUSIONS: There are many serious consequences of poor diet during pregnancy; however, most of these can be avoided by greater awareness about the role of nutrition during pregnancy and by adopting a balanced diet. RELEVANCE TO CLINICAL PRACTICE: There is an urgent unmet need for nutrition education among Ethiopian women. Research indicates that Ethiopian women are receptive to nutritional advice during pregnancy and also that pregnant women are generally motivated to act in the baby's interest. These factors suggest that this high-risk group would be amenable to culturally appropriate nutrition education, which would provide much-needed meaningful support in pregnancy. PMID- 27411856 TI - Anti-Estrogen Withdrawal Effect With Raloxifene? A Case Report. AB - A 66-year-old patient presented with acute recurrent metastatic estrogen and progesterone receptor-positive, Her-2/neu-negative breast cancer, bone lesions (lumbar spine, pelvis), pulmonary nodules, hepatic metastasis, elevated cancer antigen 15 and liver enzymes, dyspepsia, and diarrhea. The patient had been taking raloxifene for approximately 8 years. After discontinuation, clinical parameters and symptoms improved rapidly without oncological therapy or other forms of treatment. Three months after raloxifene discontinuation, capecitabine was initiated by the treating oncologist who deemed an anti-estrogen withdrawal effect (AEWE) implausible. However, the lasting regression was more indicative of a raloxifene rebound effect than chemotherapy or other interventions. Today, the patient is asymptomatic with a good performance status. Hepatic metastatic regression has been confirmed, without any oncological treatment administered in the past 16 months and approximately 23 months following the withdrawal of raloxifene. This case highlights the need to screen breast cancer patients for the possibility of an AEWE if they are using raloxifene and possibly similar selective estrogen receptor modulators (SERMs) which includes tamoxifen, when diagnosed with advanced breast cancer, especially in the recurrent disease setting. PMID- 27411857 TI - Phylogenetic evidence for a fusion of archaeal and bacterial SemiSWEETs to form eukaryotic SWEETs and identification of SWEET hexose transporters in the amphibian chytrid pathogen Batrachochytrium dendrobatidis. AB - SWEETs represent a new class of sugar transporters first described in plants, animals, and humans and later in prokaryotes. Plant SWEETs play key roles in phloem loading, seed filling, and nectar secretion, whereas the role of archaeal, bacterial, and animal transporters remains elusive. Structural analyses show that eukaryotic SWEETs are composed of 2 triple-helix bundles (THBs) fused via an inversion linker helix, whereas prokaryotic SemiSWEETs contain only a single THB and require homodimerization to form transport pores. This study indicates that SWEETs retained sugar transport activity in all kingdoms of life, and that SemiSWEETs are likely their ancestral units. Fusion of oligomeric subunits into single polypeptides during evolution of eukaryotes is commonly found for transporters. Phylogenetic analyses indicate that THBs of eukaryotic SWEETs may not have evolved by tandem duplication of an open reading frame, but rather originated by fusion between an archaeal and a bacterial SemiSWEET, which potentially explains the asymmetry of eukaryotic SWEETs. Moreover, despite the ancient ancestry, SWEETs had not been identified in fungi or oomycetes. Here, we report the identification of SWEETs in oomycetes as well as SWEETs and a potential SemiSWEET in primitive fungi. BdSWEET1 and BdSWEET2 from Batrachochytrium dendrobatidis, a nonhyphal zoosporic fungus that causes global decline in amphibians, showed glucose and fructose transport activities.-Hu, Y. B., Sosso, D., Qu, X.-Q., Chen, L.-Q., Ma, L., Chermak, D., Zhang, D.-C., Frommer, W. B. Phylogenetic evidence for a fusion of archaeal and bacterial SemiSWEETs to form eukaryotic SWEETs and identification of SWEET hexose transporters in the amphibian chytrid pathogen Batrachochytrium dendrobatidis. PMID- 27411860 TI - Element-selective resonant state in M-doped SnTe (M = Ga, In, and Tl). AB - The band engineering of M-doped SnTe (M = Ga, In, and Tl) is investigated by using first-principles calculations. Being consistent with experimental measurements, our calculations found that Ga doping hardly changes the valence band, while In doping introduces an obvious resonant state near the Fermi level. The resonant state is demonstrated to be from the anti-bonding of In-s and Te-p orbitals. Unexpectedly, no resonant state was observed in Tl-doped SnTe, indicating the nonmonotonic behavior of the Ga-In-Tl series. We show that the absence of the resonant state in Tl-doped SnTe is due to the downward shift of the Tl-s orbital, which may be attributed to the effect of lanthanide contraction. The increase of the Seebeck coefficient in In-doped SnTe is numerically confirmed by Boltzmann transport calculations. Moreover, we find that the mutually matched resonant state location and valence band separation is the key precondition for the combination of the resonant state and band convergence in SnTe. A further enhanced Seebeck coefficient (~230 MUV K(-1)) and ZT value (1.8 at 920 K) are predicted in codoped SnTe by In-Hg, owing to the synergy of two kinds of band engineering. PMID- 27411859 TI - Use of the pCONus as an adjunct to coil embolization of acutely ruptured aneurysms. AB - INTRODUCTION: Coil embolization of ruptured aneurysms has become the standard treatment in many situations. However, certain aneurysm morphologies pose technical difficulties and may require the use of adjunctive devices. OBJECTIVE: To present our experience with the pCONus, a new neck bridging device, as an adjunct to coil embolization for acutely ruptured aneurysms and discuss the technical success, angiographic and clinical outcomes. METHODS: We conducted a retrospective review of our database of prospectively collected data to identify all patients who presented with acute subarachnoid hemorrhage that required adjunctive treatment with the pCONus in the acute stage. We searched the database between April 2011 and April 2016. RESULTS: 21 patients were identified (13 male, 8 female) with an average age of 54.6 years (range 31-73). 8 aneurysms were located at the basilar artery tip, 7 at the anterior communicating artery, 4 at the middle cerebral artery bifurcation, 1 pericallosal, and 1 basilar fenestration. 61.8% patients achieved modified Raymond-Roy classification I or II at immediate angiography, with 75% of patients having completely occluded aneurysms or stable appearance at initial follow-up. There were no repeat aneurysmal ruptures and two device-related complications (no permanent morbidity). Four patients in our cohort died. CONCLUSIONS: Use of the pCONus is safe and effective in patients with acutely ruptured aneurysms and carries a high rate of technical success. PMID- 27411862 TI - Air pollution--crossing borders. PMID- 27411861 TI - Long-term Effects of Pyrethrin and Cyfluthrin, a Type II Synthetic Pyrethroid, Insecticide Applications on Bull Reproductive Parameters. AB - The objectives of this study were to determine effects of cyfluthrin and pyrethrin spray products, used in combination with cyfluthrin topical and ear tag applications, on bull reproductive parameters over 18 weeks. Angus or Angus x Simmental bulls were randomly assigned to one of three treatment groups: (i) no exposure to pyrethrins/cyfluthrin (CONT; n = 10), (ii) cyfluthrin ear tag and topical applications (ET; n = 10), or (iii) cyfluthrin ear tag, topical, premise spray and pyrethrin fog spray applications (ET+S; n = 8). Bull body weight was measured every 3 week, and body condition score and scrotal circumference were recorded on weeks 0, 9 and 18. Semen and serum were collected every 3 weeks for sperm evaluation and testosterone measurement, respectively. There was a treatment * week interaction (p < 0.01) for sperm with primary defects; bulls in CONT group had a greater (p = 0.01) percentage of sperm with primary defects than bulls treated with insecticides at week 18. Overall and progressive sperm motility, normal sperm morphology, secondary sperm defects and serum testosterone concentrations changed (p < 0.01) over time in all bulls; however, treatment did not affect (p >= 0.13) any of these parameters. There were also no treatment effects (p >= 0.08) on bull body weight, body condition score or scrotal circumference. The use of pyrethrin- and cyfluthrin-based insecticides, regardless of application, did not negatively affect reproductive parameters in beef bulls when administered over 18 weeks. PMID- 27411863 TI - Indigenous health: a worldwide focus. PMID- 27411864 TI - Harnessing primary care to reduce avoidable mortality. PMID- 27411867 TI - UK researchers digest the fallout from Brexit. PMID- 27411865 TI - Multiple myeloma--translation of trial results into reality. PMID- 27411868 TI - Conflict in Afghanistan takes an increasing toll on civilians. PMID- 27411869 TI - Blood pressure lowering for cardiovascular disease. PMID- 27411870 TI - Blood pressure lowering for cardiovascular disease. PMID- 27411871 TI - Blood pressure lowering for cardiovascular disease. PMID- 27411872 TI - Blood pressure lowering for cardiovascular disease - Authors' reply. PMID- 27411873 TI - Blood pressure lowering for cardiovascular disease. PMID- 27411874 TI - Optimum technique to reduce risk of stent thrombosis. PMID- 27411875 TI - Optimum technique to reduce risk of stent thrombosis - Authors' reply. PMID- 27411876 TI - "The Bedouin predicament". PMID- 27411877 TI - "The Bedouin predicament". PMID- 27411878 TI - Medical response to 2016 earthquake in Taiwan. PMID- 27411879 TI - Psychological support for caregivers of refugees in Greece. PMID- 27411881 TI - Tackling rheumatic heart disease in Indigenous Australians. PMID- 27411880 TI - The global response to HIV in men who have sex with men. AB - Gay, bisexual, and other men who have sex with men (MSM) continue to have disproportionately high burdens of HIV infection in countries of low, middle, and high income in 2016. 4 years after publication of a Lancet Series on MSM and HIV, progress on reducing HIV incidence, expanding sustained access to treatment, and realising human rights gains for MSM remains markedly uneven and fraught with challenges. Incidence densities in MSM are unacceptably high in countries as diverse as China, Kenya, Thailand, the UK, and the USA, with substantial disparities observed in specific communities of MSM including young and minority populations. Although some settings have achieved sufficient coverage of treatment, pre-exposure prophylaxis (PrEP), and human rights protections for sexual and gender minorities to change the trajectory of the HIV epidemic in MSM, these are exceptions. The roll-out of PrEP has been notably slow and coverage nowhere near what will be required for full use of this new preventive approach. Despite progress on issues such as marriage equality and decriminalisation of same-sex behaviour in some countries, there has been a marked increase in anti gay legislation in many countries, including Nigeria, Russia, and The Gambia. The global epidemic of HIV in MSM is ongoing, and global efforts to address it remain insufficient. This must change if we are ever to truly achieve an AIDS-free generation. PMID- 27411883 TI - Risk and other factors associated with toxoplasmosis and toxocariasis in pregnant women from southern Brazil. AB - Toxoplasmosis causes complications during pregnancy that have serious effects on fetal development. Thus far, toxocariasis has been reported to spread only via vertical transmission. Nonetheless, the population of pregnant women is also exposed to this infection. Co-infection with both Toxoplasma gondii and Toxocara spp. has been reported in children, but there are no reports of co-infection in the population of pregnant women. The aim of this study was to determine the prevalence of co-infection with T. gondii and Toxocara spp. in pregnant women at a university hospital in southern Brazil, and to identify the risk factors associated with infection by both parasites. Two hundred pregnant women were tested for the presence of anti-T. gondii and anti-Toxocara spp. antibodies and were asked to complete an epidemiological questionnaire. In this study, the co infection rate observed in the total population of pregnant women was 8%. In addition, women with a positive result for a serology test for Toxocara spp. were at increased risk of infection by T. gondii (P = 0.019). Co-infection with both parasites in pregnant women was associated with low birth weights in neonates. The similar modes of transmission of both parasites could explain the co infection. Only a few previous studies have investigated this phenomenon. The findings of the present study emphasize the importance of serological diagnosis during prenatal care and further research in this area to identify risk factors associated with this co-infection, and the possible implications of this co infection during pregnancy and on the health of newborns. PMID- 27411884 TI - New hope: the emerging role of 5-hydroxymethylcytosine in mental health and disease. AB - Historically biomedical research has examined genetic influences on mental health but these approaches have been limited, likely due to the broad heritability of brain-related disorders (e.g., 30-90%). Epigenetic modifications, such as DNA methylation, are environmentally sensitive mechanisms that may play a role in the origins and progression of mental illness. Recently, genome-wide disruptions of 5 hydroxymethylcytosine (5hmC) were associated with the development of early and late onset mental illnesses such as autism and Alzheimer's disease, bringing new hope to the field of psychiatry. Here, we review the recent links of 5hmC to mental illness and discuss several putative functions of 5hmC in the context of its promising clinical relevance. PMID- 27411885 TI - Alectinib-a new chapter in the management of ALK-positive lung cancer. PMID- 27411886 TI - Testicular Ectopia in the Anterior Abdominal Wall of a Neonate: A Rare Site of Ectopic Testis. AB - BACKGROUND Abnormal testicular descent can either be undescended or, less commonly, ectopic. Most undescended testes complete the course of descent by the first year of life only if these remain in the normal path of descent. The deviation of the testis may occur to an ectopic location during the transinguinal phase. Of the known ectopic sites, the anterior abdominal wall is the rarest site of testicular ectopia and to our knowledge only 3 cases of this nature have been reported in the available literature to date. CASE REPORT This rare case of testicular ectopia occurred in a 3-day-old boy in whom the right scrotal sac was empty; on abdominal ultrasound, the right testis was found in the subcutaneous tissues of the right antero-lateral abdominal wall. These findings were confirmed on abdominal MRI, where the right testis was seen beneath the skin between the subcutaneous tissues and external oblique aponeurosis. No aponeurotic or muscular defect was appreciable under the abdominal wall. The neonate underwent orchiopexy at the age of 6 months and remained uneventful postoperatively. CONCLUSIONS Preoperative imaging is recommended to detect and confirm the ectopic site as well as the morphology of testis, thereby increasing the chance of surveillance and preservation of an ectopic testis. Imaging can serve as preoperative road mapping to localize the exact site for surgical exploration of an ectopic testis if there is no apparent or palpable swelling over the anterior abdominal wall. PMID- 27411887 TI - Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System Modulate Immune Response in Vitro and in Vivo. AB - Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a beta-1,3-glucohexaose with beta-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 MUg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 MUg/mL) and an equivalent concentration of lentinan (3.2 MUg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity for therapeutic purposes. PMID- 27411888 TI - Time cost of diabetes: Development of a questionnaire to assess time spent on diabetes self-care. AB - BACKGROUND: Methods to measure patient time spent on health-related activities are currently not well elaborated or standardized. AIM: The purpose of this study was to develop a recall questionnaire measuring patient time devoted to diabetes self-care and to examine its feasibility and validity under field conditions. METHODS: The initial questionnaire was developed on the basis of instruments frequently used to assess self-care behavior in patients with diabetes, evaluated in two focus groups with patients with type 2 diabetes (N=15) and tested in a random sample of patients with type 2 diabetes (N=178). To assess the validity of the questionnaire, four hypotheses about expected differences in self-care time across various patient sub-groups were tested. RESULTS: The final questionnaire includes thirteen items estimating time spent on regular diabetes-related activities undertaken in the previous seven days. 78% of respondents completed the questionnaire without item non-response or other evident problems. As hypothesized, respondents receiving insulin treatment, those with poor self-rated health and those with diabetes-related emotional distress (PAID-5 score >=8) reported spending more time on diabetes self-care than the rest of the sample. Contrary to our assumption, no differences in time spent on diabetes self-care between employed and retired individuals were detected by the questionnaire. CONCLUSION: The recall questionnaire measuring patient time devoted to a broad range of regular diabetes self-care activities was developed and its feasibility was proved under field conditions. Ideally, the questionnaire should be further validated within a variety of populations. Exploration of the convergent validity between the recall method and prospective diary may be also useful. PMID- 27411889 TI - Programmed assembly of oppositely charged homogeneously decorated and Janus particles. AB - The exploitation of colloidal building blocks with morphological and functional anisotropy facilitates the generation of complex structures with unique properties, which are not exhibited by isotropic particle assemblies. Herein, we demonstrate an easy and scalable bottom-up approach for the programmed assembly of hairy oppositely charged homogeneously decorated and Janus particles based on electrostatic interactions mediated by polyelectrolytes grafted onto their surface. Two different assembly routes are proposed depending on the target structures: raspberry-like/half-raspberry-like or dumbbell-like micro-clusters. Ultimately, stable symmetric and asymmetric micro-structures could be obtained in a well-controlled manner for the homogeneous-homogeneous and homogeneous-Janus particle assemblies, respectively. The spatially separated functionalities of the asymmetric Janus particle-based micro-clusters allow their further assembly into complex hierarchical constructs, which may potentially lead to the design of materials with tailored plasmonics and optical properties. PMID- 27411891 TI - Left Bundle Branch Block and Complete Heart Block Complicating Inferior Myocardial Infarction. AB - Left bundle branch block following inferior myocardial infarction remains uncommon and scarcely reported in the literature. We describe a rare presentation of a 58-year-old male patient who developed left bundle branch block and third degree atrioventricular block after inferior myocardial infarction requiring permanent pacemaker placement. Pathophysiology, impact on mortality, and management options are discussed. PMID- 27411890 TI - Midline thalamic neurons are differentially engaged during hippocampus network oscillations. AB - The midline thalamus is reciprocally connected with the medial temporal lobe, where neural circuitry essential for spatial navigation and memory formation resides. Yet, little information is available on the dynamic relationship between activity patterns in the midline thalamus and medial temporal lobe. Here, we report on the functional heterogeneity of anatomically-identified thalamic neurons and the differential modulation of their activity with respect to dorsal hippocampal rhythms in the anesthetized mouse. Midline thalamic neurons expressing the calcium-binding protein calretinin, irrespective of their selective co-expression of calbindin, discharged at overall low levels, did not increase their activity during hippocampal theta oscillations, and their firing rates were inhibited during hippocampal sharp wave-ripples. Conversely, thalamic neurons lacking calretinin discharged at higher rates, increased their activity during hippocampal theta waves, but remained unaffected during sharp wave ripples. Our results indicate that the midline thalamic system comprises at least two different classes of thalamic projection neuron, which can be partly defined by their differential engagement by hippocampal pathways during specific network oscillations that accompany distinct behavioral contexts. Thus, different midline thalamic neuronal populations might be selectively recruited to support distinct stages of memory processing, consistent with the thalamus being pivotal in the dialogue of cortical circuits. PMID- 27411892 TI - SOX7-enforced expression promotes the expansion of adult blood progenitors and blocks B-cell development. AB - During embryogenesis, the three SOXF transcription factors, SOX7, SOX17 and SOX18, regulate the specification of the cardiovascular system and are also involved in the development of haematopoiesis. The ectopic expression of SOX17 in both embryonic and adult blood cells enhances self-renewal. Likewise, the enforced expression of SOX7 during embryonic development promotes the proliferation of early blood progenitors and blocks lineage commitment. However, whether SOX7 expression can also affect the self-renewal of adult blood progenitors has never been explored. In this study, we demonstrate using an inducible transgenic mouse model that the enforced expression of Sox7 ex vivo in bone marrow/stroma cell co-culture promotes the proliferation of blood progenitors which retain multi-lineage short-term engrafting capacity. Furthermore, SOX7 expression induces a profound block in the generation of B lymphocytes. Correspondingly, the ectopic expression of SOX7 in vivo results in dramatic alterations of the haematopoietic system, inducing the proliferation of blood progenitors in the bone marrow while blocking B lymphopoiesis. In addition, SOX7 expression induces extra-medullary haematopoiesis in the spleen and liver. Together, these data demonstrate that the uncontrolled expression of the transcription factor SOX7 in adult haematopoietic cells has dramatic consequences on blood homeostasis. PMID- 27411894 TI - Antennal Sensilla and Sexual Dimorphism of the Parasitoid Trichospilus pupivorus (Hymenoptera: Eulophidae). AB - Sensory structures (sensilla) of insects are present in high number in the antennae are important for perceiving environmental cues. Thus, sensilla play an important role in the localization, discrimination, and acceptance of a possible host by parasitoid insects. The sensilla, classified according to their shape, size, and distribution, may also show sexual dimorphism in insects. The types and distribution of antennal sensilla in female and male parasitoid Trichospilus pupivorus (Ferriere, 1930) (Hymenoptera: Eulophidae) were evaluated. T. pupivorus females had longer antennae than males. Both males and females have ten sensilla types with higher abundance of placoid sensilla in females, which suggest a possible functional dimorphism. PMID- 27411893 TI - Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain. AB - The vast majority of clinically approved protein kinase inhibitors target the ATP binding pocket directly. Consequently, many inhibitors have broad selectivity profiles and most have significant off-target effects. Allosteric inhibitors are generally more selective, but are difficult to identify because allosteric binding sites are often unknown or poorly characterized. Aurora-A is activated through binding of TPX2 to an allosteric site on the kinase catalytic domain, and this knowledge could be exploited to generate an inhibitor. Here, we generated an allosteric inhibitor of Aurora-A kinase based on a synthetic, vNAR single domain scaffold, vNAR-D01. Biochemical studies and a crystal structure of the Aurora A/vNAR-D01 complex show that the vNAR domain overlaps with the TPX2 binding site. In contrast with the binding of TPX2, which stabilizes an active conformation of the kinase, binding of the vNAR domain stabilizes an inactive conformation, in which the alphaC-helix is distorted, the canonical Lys-Glu salt bridge is broken and the regulatory (R-) spine is disrupted by an additional hydrophobic side chain from the activation loop. These studies illustrate how single domain antibodies can be used to characterize the regulatory mechanisms of kinases and provide a rational basis for structure-guided design of allosteric Aurora-A kinase inhibitors. PMID- 27411895 TI - Chronic orofacial pain. AB - The issues specific to trigeminal pain include the complexity of the region, the problematic impact on daily function and significant psychological impact (J Dent, 43, 2015, 1203). By nature of the geography of the pain (affecting the face, eyes, scalp, nose, mouth), it may interfere with just about every social function we take for granted and enjoy (J Orofac Pain, 25, 2011, 333). The trigeminal nerve is the largest sensory nerve in the body, protecting the essential organs that underpin our very existence (brain, eyes, nose, mouth). It is no wonder that pain within the trigeminal system in the face is often overwhelming and inescapable for the affected individual. PMID- 27411896 TI - Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children. AB - INTRODUCTION: Modification of alarm limits is one approach to mitigating alarm fatigue. We aimed to create and validate heart rate (HR) and respiratory rate (RR) percentiles for hospitalized children, and analyze the safety of replacing current vital sign reference ranges with proposed data-driven, age-stratified 5th and 95th percentile values. METHODS: In this retrospective cross-sectional study, nurse-charted HR and RR data from a training set of 7202 hospitalized children were used to develop percentile tables. We compared 5th and 95th percentile values with currently accepted reference ranges in a validation set of 2287 patients. We analyzed 148 rapid response team (RRT) and cardiorespiratory arrest (CRA) events over a 12-month period, using HR and RR values in the 12 hours prior to the event, to determine the proportion of patients with out-of-range vitals based upon reference versus data-driven limits. RESULTS: There were 24,045 (55.6%) fewer out-of-range measurements using data-driven vital sign limits. Overall, 144/148 RRT and CRA patients had out-of-range HR or RR values preceding the event using current limits, and 138/148 were abnormal using data-driven limits. Chart review of RRT and CRA patients with abnormal HR and RR per current limits considered normal by data-driven limits revealed that clinical status change was identified by other vital sign abnormalities or clinical context. CONCLUSIONS: A large proportion of vital signs in hospitalized children are outside presently used norms. Safety evaluation of data-driven limits suggests they are as safe as those currently used. Implementation of these parameters in physiologic monitors may mitigate alarm fatigue. Journal of Hospital Medicine 2015;11:817-823. (c) 2015 Society of Hospital Medicine. PMID- 27411897 TI - Does cognitive decline decrease health utility value in older adult patients with cancer? AB - AIM: Cognitive decline is common among older adults with cancer. The present study aimed to investigate the impact of cognitive decline on health utility value in older adults suffering from cancer. METHODS: Consecutive patients aged 65 years or older with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Patients were asked to complete the EuroQoL-5 (EQ-5D) scale to measure health utility and the Mini-Mental State Examination to assess cognitive decline. The potential impact of cognitive decline was investigated with univariate analysis. A multivariate regression analysis was conducted to control for potential confounding factors. RESULTS: Complete data were obtained from 87 patients, 29% of whom had cognitive decline. The mean +/- SE EQ-5D score for patients with cognitive decline was significantly lower than that for those without cognitive decline (0.67 +/- 0.04 vs 0.79 +/- 0.03, t = 2.38, P = 0.02). However, multiple regression analysis showed that cognitive decline was not significantly associated with EQ-5D scores. Female sex and lower performance scores (worse physical condition) were significantly associated with EQ-5D scores. CONCLUSIONS: Cognitive decline may be involved in decreased health utility value in older adult patients with cancer. However, this effect does not seem to be independent, and the patient's physical condition may be a relevant confounding factor. PMID- 27411898 TI - Analysis of the mouse gut microbiome using full-length 16S rRNA amplicon sequencing. AB - Demands for faster and more accurate methods to analyze microbial communities from natural and clinical samples have been increasing in the medical and healthcare industry. Recent advances in next-generation sequencing technologies have facilitated the elucidation of the microbial community composition with higher accuracy and greater throughput than was previously achievable; however, the short sequencing reads often limit the microbial composition analysis at the species level due to the high similarity of 16S rRNA amplicon sequences. To overcome this limitation, we used the nanopore sequencing platform to sequence full-length 16S rRNA amplicon libraries prepared from the mouse gut microbiota. A comparison of the nanopore and short-read sequencing data showed that there were no significant differences in major taxonomic units (89%) except one phylotype and three taxonomic units. Moreover, both sequencing data were highly similar at all taxonomic resolutions except the species level. At the species level, nanopore sequencing allowed identification of more species than short-read sequencing, facilitating the accurate classification of the bacterial community composition. Therefore, this method of full-length 16S rRNA amplicon sequencing will be useful for rapid, accurate and efficient detection of microbial diversity in various biological and clinical samples. PMID- 27411900 TI - Developing a theory of change for a community-based response to illegal wildlife trade. AB - The escalating illegal wildlife trade (IWT) is one of the most high-profile conservation challenges today. The crisis has attracted over US$350 million in donor and government funding in recent years, primarily directed at increased enforcement. There is growing recognition among practitioners and policy makers of the need to engage rural communities that neighbor or live with wildlife as key partners in tackling IWT. However, a framework to guide such community engagement is lacking. We developed a theory of change (ToC) to guide policy makers, donors, and practitioners in partnering with communities to combat IWT. We identified 4 pathways for community-level actions: strengthen disincentives for illegal behavior, increase incentives for wildlife stewardship, decrease costs of living with wildlife, and support livelihoods that are not related to wildlife. To succeed the pathways, all require strengthening of enabling conditions, including capacity building, and of governance. Our ToC serves to guide actions to tackle IWT and to inform the evaluation of policies. Moreover, it can be used to foster dialogue among IWT stakeholders, from local communities to governments and international donors, to develop a more effective, holistic, and sustainable community-based response to the IWT crisis. PMID- 27411901 TI - A new set of rDNA-NTS-based multiple integrative cassettes for the development of antibiotic-marker-free recombinant yeasts. AB - The traditional yeast Saccharomyces cerevisiae has been widely used as a host system to produce recombinant proteins and metabolites of great commercial value. To engineer recombinant yeast that stably maintains expression cassettes without an antibiotic resistance gene, we developed new multiple integration cassettes by exploiting the non-transcribed spacer (NTS) of ribosomal DNA (rDNA) in combination with defective selection markers. The 5' and 3'-fragments of rDNA NTS2 were used as flanking sequences for the expression cassettes carrying a set of URA3, LEU2, HIS3, and TRP1 selection markers with truncated promoters of different lengths. The integration numbers of NTS-based expression cassettes, ranging from one to ~30 copies, showed a proportional increase with the extent of decreased expression of the auxotrophic markers. The NTS-based cassettes were used to construct yeast strains expressing the capsid protein of red-spotted grouper necrosis virus (RG-NNVCP) in a copy number-dependent manner. Oral administration of the recombinant yeast, harboring ~30 copies of the integrated RG-NNVCP cassettes, provoked efficient immune responses in mice. In contrast, for the NTS cassettes expressing a truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, the integrant carrying only 4 copies was screened as the highest producer of squalene, showing a 150-fold increase compared to that of the wild type strain. The multiple integrated cassettes were stably retained under prolonged nonselective conditions. Altogether, our results strongly support that rDNA-NTS integrative cassettes are useful tools to construct recombinant yeasts carrying optimal copies of a desired expression cassette without an antibiotic marker gene, which are suitable as oral vaccines or feed additives for animal and human consumption. PMID- 27411902 TI - Synthesis of an artificial Vitis vinifera miRNA 319e using overlapping long primers and its application for gene silencing. AB - The conserved mechanism of action of micro-RNAs (miRNAs) as regulators of gene expression has allowed the use of artificial miRNAs (amiRNAs) as a powerful tool for candidate gene evaluation in plants. Based on the use of a Vitis vinifera miRNA molecule (i.e., vvi-miR319e), the present work presents a new methodology for designing artificial miR319e precursors (pre-amiR319e). As a proof of concept, we silenced the green fluorescent protein (GFP) gene in transgenic Nicotiana benthamiana plants. This methodology includes a two-step PCR reaction in which overlapping long primers allow for the complete generation of pre amiR319e-GFP molecules that are adequate for recombination into Gateway vectors with no further requirements. The seed region in amiRNA was directed against the 3'-end portion of the GFP gene. Three groups of transformed N. benthamiana plants were generated: GFP-, amiR319e-GFP-, and GFP plus miR319e-GFP-expressing vectors. A similar group of wild-type plants was included. Confocal microscopy evaluation of these groups revealed strong silencing of the GFP phenotype in the double GFP plus amiR319e-GFP group. The molecular characterization of silenced plants was achieved via modified 5'RACE of the GFP mRNA and revealed the occurrence of a partial, 3'-end GFP mRNA molecule that was generated in planta. In addition, large-scale small RNA sequencing confirmed the occurrence of the expected 21-nt miR319e-GFP species and other 22- and 24-nt species that exhibited sequence relationships with the expected amiRNA. These results highlight the possibility of using vvi-MIR319 as a template for the generation of single amiRNAs as a tool for gene silencing in plants. PMID- 27411903 TI - Safety and postoperative adverse events in pediatric airway reconstruction: Analysis of ACS-NSQIP-P 30-day outcomes. AB - OBJECTIVES: Prior research has shown that airway reconstructive procedures comprise significant composite morbidity compared to the whole of pediatric otolaryngologic cases evaluated in the American College of Surgeon's National Surgery Quality Improvement Program-Pediatric (ACS-NSQIP-P) platform. We describe postoperative sequelae of pediatric airway reconstructive procedures and identify predictive factors for adverse events. METHODS: Current procedural terminology (CPT) codes were used to identify children undergoing included procedures in the 2012 to 2014 ACS-NSQIP-P public use files (PUF). Targeted variables included patient demographics and 30-day postoperative events (reoperation, readmission, and complications). Event rates were determined and compared within subgroups. Multivariate logistic regression was performed to identify predictive factors for major adverse events. RESULTS: In 3 years of PUF data (183,283 total cases), 198 cases (0.11%) were airway reconstructive procedures. The most common was laryngoplasty (CPT 31580, 31582; n = 111, 56.1%), followed by cervical tracheoplasty (CPT 31750; n = 47, 23.7%), tracheal resection (CPT 31780; n = 24, 12.1%), and cricoid split (CPT 31587, n = 16, 8.1%). There were 131 premature children (66.2%) and 94 children (47.5%) with history of bronchopulmonary dysplasia. Thirty-day postoperative sequelae included readmissions (n = 42, 21.2%), complications (n = 27, 13.6%), and reoperations (n = 14, 7.1%). On univariate analysis, children less than 3 years of age were more likely to undergo an unplanned reoperation. There were no significant predictive factors for readmission or complication. On multivariate analysis, there was a trend toward higher rates of unplanned reoperations in children less than 3 years of age. CONCLUSION: The 30-day adverse event rate in pediatric airway surgery is high, with no identifiable predictors noted in the analysis of these data. Findings imply that systematic collection of variables and outcomes specific to pediatric airway surgery, in addition to standard NSQIP workflow, will be essential for NSQIP-P to truly effect quality improvement in these high-risk procedures. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016 127:504-508, 2017. PMID- 27411904 TI - Autoimmunity: Interferon alpha or beta: which is the culprit in autoimmune disease? PMID- 27411905 TI - Autoimmunity: DNASE1L3 prevents anti-DNA responses. PMID- 27411908 TI - Deregulation and therapeutic potential of microRNAs in arthritic diseases. PMID- 27411906 TI - Insight into rheumatological cause and effect through the use of Mendelian randomization. AB - Establishing causality of risk factors is important to determine the pathogenetic mechanisms underlying rheumatic diseases, and can facilitate the design of interventions to improve care for affected patients. The presence of unmeasured confounders, as well as reverse causation, is a challenge to the assignment of causality in observational studies. Alleles for genetic variants are randomly inherited at meiosis. Mendelian randomization analysis uses these genetic variants to test whether a particular risk factor is causal for a disease outcome. In this Review of the Mendelian randomization technique, we discuss published results and potential applications in rheumatology, as well as the general clinical utility and limitations of the approach. PMID- 27411909 TI - Vasculitis syndromes: Updated recommendations for ANCA-associated vasculitis - working together. PMID- 27411907 TI - Treatment of primary Sjogren syndrome. AB - Primary Sjogren syndrome (pSS) is a progressive autoimmune disease characterized by sicca and systemic manifestations. In this Review, we summarize the available data on topical and systemic medications, according to clinical signs and disease activity, and we describe the ongoing studies using biologic drugs in the treatment of pSS. Expanding knowledge about the epidemiology, classification criteria, systemic activity scoring (ESSDAI) and patient-reported outcomes (ESSPRI) is driving active research. Treatment decisions are based on the evaluation of symptoms and extraglandular manifestations. Symptomatic treatment is usually appropriate, whereas systemic treatment is reserved for systemic manifestations. Sicca is managed by education, environment modification, elimination of contingent offending drugs, artificial tears, secretagogues and treatments for complications. Mild systemic signs such as fatigue are treated by exercise. Pain can require short-term moderate-dose glucocorticoid therapy and, in some cases, disease-modifying drugs. Severe and acute systemic manifestations indicate treatment with glucocorticoids and/or immunosuppressant drugs. The role for biologic agents is promising, but no double-blind randomized controlled trials (RCTs) proving the efficacy of these drugs are available. Targets for new treatments directed against the immunopathological mechanisms of pSS include epithelial cells, T cells, B-cell overactivity, the interferon signature, proinflammatory cytokines, ectopic germinal centre formation, chemokines involved in lymphoid cell homing, and epigenetic modifications. PMID- 27411911 TI - The sucrose non-fermenting 1-related kinase 2 gene SAPK9 improves drought tolerance and grain yield in rice by modulating cellular osmotic potential, stomatal closure and stress-responsive gene expression. AB - BACKGROUND: Family members of sucrose non-fermenting 1-related kinase 2 (SnRK2), being plant-specific serine/threonine protein kinases, constitute the central core of abscisic acid (ABA)-dependent and ABA-independent signaling pathways, and are key regulators of abiotic stress adaptation in plants. We report here the functional characterization of SAPK9 gene, one of the 10 SnRK2s of rice, through developing gain-of-function and loss-of-function phenotypes by transgenesis. RESULTS: The gene expression profiling revealed that the abundance of single gene derived SAPK9 transcript was significantly higher in drought-tolerant rice genotypes than the drought-sensitive ones, and its expression was comparatively greater in reproductive stage than the vegetative stage. The highest expression of SAPK9 gene in drought-tolerant Oryza rufipogon prompted us to clone and characterise the CDS of this allele in details. The SAPK9 transcript expression was found to be highest in leaf and upregulated during drought stress and ABA treatment. In silico homology modelling of SAPK9 with Arabidopsis OST1 protein showed the bilobal kinase fold structure of SAPK9, which upon bacterial expression was able to phosphorylate itself, histone III and OsbZIP23 as substrates in vitro. Transgenic overexpression (OE) of SAPK9 CDS from O. rufipogon in a drought-sensitive indica rice genotype exhibited significantly improved drought tolerance in comparison to transgenic silencing (RNAi) lines and non-transgenic (NT) plants. In contrast to RNAi and NT plants, the enhanced drought tolerance of OE lines was concurrently supported by the upgraded physiological indices with respect to water retention capacity, soluble sugar and proline content, stomatal closure, membrane stability, and cellular detoxification. Upregulated transcript expressions of six ABA-dependent stress responsive genes and increased sensitivity to exogenous ABA of OE lines indicate that the SAPK9 is a positive regulator of ABA-mediated stress signaling pathways in rice. The yield-related traits of OE lines were augmented significantly, which resulted from the highest percentage of fertile pollens in OE lines when compared with RNAi and NT plants. CONCLUSION: The present study establishes the functional role of SAPK9 as transactivating kinase and potential transcriptional activator in drought stress adaptation of rice plant. The SAPK9 gene has potential usefulness in transgenic breeding for improving drought tolerance and grain yield in crop plants. PMID- 27411913 TI - The psychosocial determinants of the intention to avoid sexual engagement when intoxicated among young men in KwaZulu-Natal, South Africa. AB - BACKGROUND: A cross sectional study was conducted among 350 sexually active, mainly unemployed men between the ages of 18 and 35 in KwaZulu-Natal. This study examined the psychosocial determinants of the intention to be sexually active after having used marijuana or alcohol personally or in instances when the sexual partner is intoxicated. The theory of planned behaviour and cultural notions of responsible manhood were used in developing the measures. METHODS: Correlation and hierarchical stepwise linear regression analyses tested determinants of the intention to avoid having sex when personally intoxicated and the intention to avoid sex when the sexual partner is intoxicated. RESULTS: About 78 % of the participants reported regular use of alcohol and 39 % indicated ever-using marijuana. A total of 36.3 % used both alcohol and marijuana, and 73 % said that they engaged in multiple sexual partner behaviour. The intention to avoid sex when personally intoxicated as well as the intention to avoid sex when the sexual partner is intoxicated were significantly associated with subjective norms and perceptions of perceived behavioural control towards the respective behaviours, and less with attitudes towards the respective behaviours. CONCLUSIONS: These findings imply that health education interventions should focus on changing the normative beliefs as well as control beliefs of the target population either directly through education and training or indirectly by creating physical and social environments that facilitate safe sexual practices, for example by organizing positive peer support for risk prevention and by making condoms freely available in community alcohol serving establishments. PMID- 27411912 TI - Abducens nerve palsy as a postoperative complication of minimally invasive thoracic spine surgery: a case report. AB - BACKGROUND: Thoracic disc surgeries make up only a small number of all spine surgeries performed, but they can have a considerable number of postoperative complications. Numerous approaches have been developed and studied in an attempt to reduce the morbidity associated with the procedure; however, we still encounter cases that develop serious and unexpected outcomes. CASE PRESENTATION: This case report presents a patient with abducens nerve palsy after minimally invasive surgery for thoracic disc herniation with an intraoperative spinal fluid fistula. A literature review of all cases related to this complication after spine surgery is included. Despite the uncommon nature of this type of complication, understanding the procedure itself, the principle occurrences and outcomes following the procedure, the physiopathogical features of abducens nerve palsy, and the possible adverse effects of spinal surgery, including minimally invasive procedures, can enable an early diagnosis of complications and facilitate the procedure. CONCLUSIONS: In spite of being very rare and multifactorial, uni- or bilateral abducens nerve paralysis carries significant morbidity and can occur as a postoperative complication after conventional or minimally invasive spine surgery. This condition requires an accurate diagnosis and adequate multidisciplinary follow up. PMID- 27411915 TI - ERRATUM. PMID- 27411910 TI - Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways. AB - In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) have an increased prevalence of some mental health disorders, particularly those involving affective or mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and their psychological responses to the disease, and can also impair responses to treatment through disruption of patient-physician relationships and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed. PMID- 27411914 TI - Pleural fluid osteopontin, vascular endothelial growth factor, and urokinase-type plasminogen activator levels as predictors of pleurodesis outcome and prognosticators in patients with malignant pleural effusion: a prospective cohort study. AB - BACKGROUND: Rapidly growing cancer cells secrete growth-promoting polypeptides and have increased proteolytic activity, contributing to tumor progression and metastasis. Their presentation in malignant pleural effusion (MPE) and their predictive value for the outcome of pleurodesis and survival were studied. METHODS: Between February 2011 and March 2012, MPE samples were prospectively collected from 61 patients. Twenty-five patients with non-malignant pleural effusion in the same period were included as controls. Pleural fluid osteopontin (OPN), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) concentrations were measured. RESULTS: Patients with MPE had higher pleural fluid OPN, VEGF, and uPA concentrations than those with non malignant pleural effusion, but only differences in VEGF were statistically significant (p = 0.045). Patients with distant metastases had significantly elevated pleural fluid VEGF concentrations than those without (p = 0.004). Pleural fluid OPN, VEGF, and uPA concentrations were positively correlated in most patients. However, there was no significant difference in pleural fluid OPN, VEGF, and uPA concentrations between patients with successful pleurodesis and those without. There was also no significant difference in cancer-specific survival between sub-groups with higher and lower pleural fluid OPN, VEGF, or uPA concentrations. Patients with successful pleurodesis had significantly longer cancer-specific survival than those without (p = 0.015). CONCLUSIONS: Pleural fluid OPN, VEGF, and uPA concentrations are elevated in MPE but are not satisfactory predictors of pleurodesis outcome or survival. Patients with higher pleural fluid VEGF concentration have higher risk of distant metastasis. Evaluating the benefits of therapy targeting the VEGF pathway in these patients warrants further studies. PMID- 27411917 TI - [Lung cancer screening with thoracic X-ray and CT : Current situation]. AB - CLINICAL/METHODICAL ISSUE: Attempts at the early detection of lung cancer using imaging methods began as far back as the 1950s. STANDARD RADIOLOGICAL METHODS: Several studies attempted to demonstrate a reduction of lung cancer mortality by chest radiography screening but all were unsuccessful. METHODICAL INNOVATIONS: Even the first small screening studies using computed tomography (CT) could not demonstrate a reduction in lung cancer-specific mortality until in 2011 the results of the largest randomized controlled low-dose CT screening study in the USA (NLST) were published. The NLST results could show a significant 20 % reduction of lung cancer mortality in elderly and heavy smokers using CT. PERFORMANCE: Confirmation of the NLST results are urgently needed so that the data of the largest European study (NELSON) are eagerly awaited. ACHIEVEMENTS: Pooled with the data from several smaller European studies these results will provide important information and evidence for the establishment of future CT screening programs in Europe. PRACTICAL RECOMMENDATIONS: Randomized controlled trials are the basis of evidence-based medicine; therefore, the positive results of the methodologically very good NLST study cannot be ignored, even if it is the only such study completed so far with highly convincing conclusions. The NLST results clearly demonstrate that positive effects for the health of the population can only be expected if the processes are clearly defined and the quality is assured. PMID- 27411918 TI - [Impingement of the hip]. AB - Femoroacetabular impingement (FAI) describes the repetitive painful contact between the acetabulum, the pelvis and the proximal femur. This bony abutment can lead to a characteristic pattern of chondrolabral damage and is one of the main etiological factors in the development of juvenile osteoarthritis of the hip joint. This article describes the current treatment concepts of FAI and the radiological assessment including an overview of standard measurement methods, coxometric parameters and cut-off values. Furthermore, the authors stress the importance of a profound understanding of the entire configuration of the pelvis and the dynamic interplay of its components. PMID- 27411919 TI - Expression of P53 and isoforms in bening and malignant lesions of the head and neck. AB - BACKGROUND: P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. METHODS: By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). RESULTS: In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. CONCLUSIONS: We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions. PMID- 27411920 TI - Inhibition of the oxidative stress-induced miR-23a protects the human retinal pigment epithelium (RPE) cells from apoptosis through the upregulation of glutaminase and glutamine uptake. AB - The degeneration of retinal pigment epithelium (RPE) cells in the sub retinal pigment epithelial space and choroid is an initial pathological characteristic for the age-related macular degeneration which is the leading cause of severe vision loss in old people. Moreover, oxidative stress is implicated as a major inducer of RPE cell death. Here, we assessed the correlation between the H2O2 induced RPE cell death and glutamine metabolism. We found under low glutamine supply (20 %), the ARPE-19 cells were more susceptive to H2O2-induced apoptosis. Moreover, the glutamine uptake and the glutaminase (GLS) were suppressed by H2O2 treatments. Moreover, we observed miR-23a was upregulated by H2O2 treatments and overexpression of miR-23a significantly sensitized ARPE-19 cells to H2O2. Importantly, Western blotting and luciferase assay demonstrated GLS1 is a direct target of miR-23a in RPE cells. Inhibition of the H2O2-induced miR-23a by antagomiR protected the RPE cells from the oxidative stress-induced cell death. In addition, recovery of GLS1 expression in miR-23a overexpressed RPE cells rescued the H2O2-induced cell death. This study illustrated a mechanism for the protection of the oxidative-induced RPE cell death through the recovery of glutamine metabolism by inhibition of miR-23a, contributing to the discovery of novel targets and the developments of therapeutic strategies for the prevention of RPE cells from oxidative stress. PMID- 27411921 TI - Lysobacter erysipheiresistens sp. nov., an antagonist of powdery mildew, isolated from tobacco-cultivated soil. AB - A bacterial strain, RS-LYSO-3T, was isolated from tobacco-cultivated soil, collected near Chuxiong, Yunnan province, southwestern China. RS-LYSO-3T could effectively inhibit the invasion of powdery mildew on tobacco. The colonies of RS LYSO-3T were pale yellow, and its cells were Gram-stain-negative and rod-shaped, with 68 mol% DNA G+C content. Gene sequence analysis for its 16S rRNA gene revealed the highest similarity (97.78 %) with that of Lysobacter spongiicolaKMM 329T. Chemotaxonomic data showed that RS-LYSO-3T possesses a quinone system with Q-8, and iso-C16 : 0, summed feature 9 and iso-C15 : 0 as the predominant fatty acids, all of which support the affiliation of RS-LYSO-3T to the genus Lysobacter. The results of DNA-DNA hybridization, physiological and biochemical tests clearly proved that RS-LYSO-3T is a representative of a novel species of the genus Lysobacter, for which the name Lysobacter erysipheresistens sp. nov. is proposed. The type strain is RS-LYSO-3T (=CCIC 23922T=JCM 31042T). PMID- 27411922 TI - The Expression of Checkpoint and DNA Repair Genes in Head and Neck Cancer as Possible Predictive Factors. AB - DNA damage response failure may influence the efficacy of DNA-damaging treatments. We determined the expression of 16 genes involved in distinct DNA damage response pathways, in association with the response to standard therapy. Twenty patients with locoregionally advanced, squamous cell head and neck carcinoma were enrolled. The treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy (ChRT) or radiotherapy (RT) alone. The volumetric metabolic therapeutic response was determined by [18F]FDG-PET/CT. In the tumor and matched normal tissues collected before treatment, the gene expressions were examined via the quantitative real-time polymerase chain reaction (qRT-PCR). The down regulation of TP53 was apparently associated with a poor response to iChT, its up regulation with complete regression in 2 cases. 7 cases with down-regulated REV1 expression showed complete regression after ChRT/RT, while 1 case with REV1 overexpression was resistant to RT. The overexpression of WRN was an independent predictor of tumor relapse. Our results suggest that an altered expression of REV1 predicts sensitivity to RT, while WRN overexpression is an unfavorable prognostic factor. PMID- 27411923 TI - Low Expression LncRNA TUBA4B is a Poor Predictor of Prognosis and Regulates Cell Proliferation in Non-Small Cell Lung Cancer. AB - We aimed to unveil the clinical roles and biological function of lncRNA TUBA4B in on-small cell lung cancer (NSCLC). The relative expression level of TUBA4B was estimated by qPCR in 114 pairs of NSCLC and NT samples and the relation of TUBA4B to clinical data of NSCLC patients was analyzed. We found TUBA4B was lower expressed in NSCLC and five cell lines. The lower expression of TUBA4B was remarkably correlated with advanced TNM stage and lymph node metastasis and served as a predictor for overall survival of NSCLC. After overexpression of TUBA4B, cell proliferation ability of A549 and NCI-H1299 remarkably decreased. Our study ascertained low expression TUBA4B in NSCLC tissue, cell lines and is a poor predictor for prognosis and can regulate cell proliferation in NSCLC. PMID- 27411924 TI - Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer. AB - A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study. These patients were classified into 4 groups: 39 with adenocarcinoma with (n = 19) and without (n = 20) diabetes, and 40 with squamous cell carcinoma with (n = 20) and without (n = 20) diabetes. Immunohistochemical expression of eight EMT markers was analyzed, including transforming growth factor-beta (TGF-beta), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), vimentin, E cadherin, N-cadherin, HtrA1, and beta-catenin. Five markers (E-cadherin, HtrA1, TGF-beta, IGF-1R and vimentin) demonstrated significantly higher expression in diabetics than in non-diabetics in both histology types. N-cadherin had higher expression in diabetics, though the difference did not reach statistical significance. EGFR showed a higher expression in diabetics in squamous cell carcinoma only. Beta-catenin was the only marker with no difference in expression between diabetics versus non-diabetics. Our findings suggest that diabetes is associated with enhanced EMT in NSCLC, which may contribute to growth and invasiveness of NSCLC. PMID- 27411925 TI - Effects of soil nitrogen availability and native grass diversity on exotic forb dominance. AB - Exotic plants are often most successful in high resource environments. By drawing down available resources, species-rich communities may be able to reduce exotic success when resource supply is elevated. We tested the prediction that exotic success would be greatest in species-poor communities when nitrogen availability is high. We also tested two underlying assumptions of this prediction: species rich communities draw down soil nitrogen availability more than species-poor communities following fertilization and exotic success increases when soil nitrogen availability is high. In a restored grassland where native grass diversity was manipulated (one, three, or five-species) seven years earlier to form a gradient in species richness, we manipulated nitrogen availability directly via fertilization, and indirectly via burning. We then examined the success of the exotic forb Galium verum L. Contrary to our prediction, diversity and nutrient treatments did not jointly influence exotic success. Instead, one time fertilization increased exotic biomass in the first year of the study. This likely occurred because the effect of nutrient treatments on nitrogen availability was independent of diversity treatment. Thus, we found no evidence that species-rich communities are better able to reduce exotic biomass when nitrogen is added than are species-poor communities. This suggests that in some systems, the effects of increasing species richness can be overwhelmed by the effects of nutrient addition that promote exotic success. PMID- 27411926 TI - Effects of Different Dietary Selenium Sources on Antioxidant Status and Blood Phagocytic Activity in Sheep. AB - The objective of this experiment was to investigate the effects of feed supplementation with equivalent doses of selenium from sodium selenite (SS) or selenized yeast (SY) on Se deposition, selenoenzyme activity and lipid peroxidation in tissues as well as in bacterial and protozoal fractions of rumen contents in sheep. The phagocytic activity of monocytes and neutrophils in whole blood was also assessed after 3 months of dietary treatment. While animals in the control group were fed with unsupplemented basal diet (BD) containing only background Se (0.16 mg/kg DM), the diet of the other two groups (n = 6) consisted of identical BD enriched with 0.4 mg Se/kg DM either from SS or SY. Concentrations of Se in blood and tissues were found to be significantly increased in both supplemented groups. No response in Se deposition was recorded in the musculus longissimus dorsi of sheep given dietary SS. The intake of SY resulted in a significantly higher Se level in the blood, kidney medulla, skeletal muscles, heart, intestinal and ruminal mucosa than in the case of SS supplementation. No differences appeared between tissue Se contents in the liver and kidney cortex due to the source of added Se. Regardless of source, Se supplementation to feeds significantly increased the glutathione peroxidase (GPx) activity in blood and tissues except the kidney medulla and jejunal mucosa. Supplementation with SY resulted in significantly higher activity of thioredoxin reductase in the liver and ileal mucosa, and also reduced malondialdehyde content in the liver and duodenal mucosa. Dietary Se intake increased Se concentrations in the total rumen contents and bacterial and protozoal fractions. The accumulation of Se in rumen microbiota was associated with increased GPx activity. Phagocytic cell activity was enhanced by Se supplementation. Our results indicate that Se from both sources has beneficial effects on antioxidant status in sheep and can be utilized by rumen microflora. PMID- 27411927 TI - In Vitro Toxicological Assessment of Cobalt Ferrite Nanoparticles in Several Mammalian Cell Types. AB - Nanoparticles have been widely used in various fields due to the superior physicochemical properties and functions. As a result, human exposure to nanoparticles increases dramatically. Previous researches have shown that nanoparticles could travel through the respiratory, digestive system, or skin into the blood and then to the secondary organs such as the brain, heart, and liver. Besides, the nanoparticle toxicity is controversial and dependent on the sensitivity of the cell type, route of exposure, and condition, as well as their characteristics. Similarly, cobalt ferrite nanoparticles (CoFe2O4-NPs) have been used in different industrial fields, and have also various application possibilities in medical and biomedical fields. CoFe2O4-NPs induce toxic responses in various organisms such as human, mice, and algae. However, there is a serious deficit of information concerning their effects on human health and the environment. We aimed to investigate the toxic effects of CoFe2O4-NPs on liver (HepG2), colon (Caco-2), lung (A549), and neuron (SH-SY5Y) cells, which reflect different exposure routes in vitro, by using various toxicological endpoints. The cytotoxicity, genotoxicity, oxidative damage, and apoptosis induction of CoFe2O4 NPs (39 +/- 17 nm) were evaluated. After 24 h, the nanoparticles decreased cell viability at <=100 MUg/mL, while increasing viability at >100 MUg/mL. CoFe2O4-NPs induced DNA and oxidative damage with increased malondialdehyde (MDA) and 8 hydroxy deoxyguanosine (8-OHdG) levels and decreased glutathione (GSH) levels with no change in protein carbonyl (PC) levels. CoFe2O4-NPs had apoptotic effect in HepG2 and Caco-2 cells in a concentration-dependent manner and necrotic effects on SH-SY5Y and A549 cells. Consequently, the adverse effects of CoFe2O4 NPs should raise concern about their safety in consumer products. PMID- 27411929 TI - pH-dependent conformational changes of a Thogoto virus matrix protein reveal mechanisms of viral assembly and uncoating. AB - Orthomyxoviruses are a family of ssRNA virus, including influenza virus, infectious salmon anaemia virus and Thogoto virus. The matrix proteins of orthomyxoviruses play crucial roles in some essential processes of the viral life cycle. However, the mechanisms of the matrix proteins involved in these processes remain incompletely understood. Currently, only the structure and function of the matrix protein from influenza virus have been studied. Here, we present the crystal structures of the N-terminal domain of matrix protein from Thogoto virus at pH 7.0 and 4.5. By analysing the structures, we identified the conformational changes of monomers and dimers in different pH conditions, mainly caused by two flexible loops, L3 and L5. These structural deviations would reflect the basis of viral capsid assembly or disassembly. PMID- 27411928 TI - Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis. AB - Subclinical mastitis is a widely spread disease of lactating cows. Its major pathogen is Staphylococcus aureus (S. aureus). In this study, we performed genome wide integrative analysis of DNA methylation and transcriptional expression to identify candidate genes and pathways relevant to bovine S. aureus subclinical mastitis. The genome-scale DNA methylation profiles of peripheral blood lymphocytes in cows with S. aureus subclinical mastitis (SA group) and healthy controls (CK) were generated by methylated DNA immunoprecipitation combined with microarrays. We identified 1078 differentially methylated genes in SA cows compared with the controls. By integrating DNA methylation and transcriptome data, 58 differentially methylated genes were shared with differently expressed genes, in which 20.7% distinctly hypermethylated genes showed down-regulated expression in SA versus CK, whereas 14.3% dramatically hypomethylated genes showed up-regulated expression. Integrated pathway analysis suggested that these genes were related to inflammation, ErbB signalling pathway and mismatch repair. Further functional analysis revealed that three genes, NRG1, MST1 and NAT9, were strongly correlated with the progression of S. aureus subclinical mastitis and could be used as powerful biomarkers for the improvement of bovine mastitis resistance. Our studies lay the groundwork for epigenetic modification and mechanistic studies on susceptibility of bovine mastitis. PMID- 27411930 TI - Advances in the Treatment of Non-small Cell Lung Cancer: Focus on Nivolumab, Pembrolizumab, and Atezolizumab. AB - Immunotherapy is revolutionizing the treatment of non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, including programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) monoclonal antibodies, are being introduced to routine clinical practice. This review summarizes clinical trials of nivolumab, pembrolizumab, and atezolizumab in patients with NSCLC. These agents have efficacy against NSCLC and a unique toxicity profile. The role of PD-L1 as a predictive biomarker is still unclear, partially because of the nuances of PD-L1 testing. These novel therapies also challenge our existing methodologies of radiologic assessment and efficacy analysis. This new era of immunotherapy has ushered in as much hope for patients as questions from physicians that need to be answered to clarify the optimal use of these agents. PMID- 27411931 TI - Comparative genomics provides insight into maize adaptation in temperate regions. AB - A new study provides insights into the evolution of maize during its global spread into temperate regions from its origin in coastal Mexico.Please see related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1009-x. PMID- 27411932 TI - A Halogen-Bond-Induced Triple Helicate Encapsulates Iodide. AB - The self-assembly of higher-order anion helicates in solution remains an elusive goal. Herein, we present the first triple helicate to encapsulate iodide in organic and aqueous media as well as the solid state. The triple helicate self assembles from three tricationic arylethynyl strands and resembles a tubular anion channel lined with nine halogen bond donors. Eight strong iodine???iodide halogen bonds and numerous buried pi-surfaces endow the triplex with remarkable stability, even at elevated temperatures. We suggest that the natural rise of a single-strand helix renders its linear halogen-bond donors non-convergent. Thus, the stringent linearity of halogen bonding is a powerful tool for the synthesis of multi-strand anion helicates. PMID- 27411933 TI - Cesarean Birth Regret and Dissatisfaction: A Qualitative Approach. AB - BACKGROUND: The most consistently noted difference between unplanned cesarean and vaginal births is patient dissatisfaction or regret. This has been explored in multiple quantitative studies. However, the causes of this dissatisfaction remain elusive as a result of the limitations of survey instruments that restrict possible choices. METHODS: Using open-ended, semi-structured interviews (n = 14), the purpose of this study was to identify potentially alterable factors that contribute to cesarean section regret when the surgery is performed during labor. In interviews that took place between 2 and 6 weeks postpartum, patients who had undergone an unscheduled cesarean birth during labor and had volunteered for the study were asked to share the story of their birth. Each participant was prompted to describe her understanding of the indication for her cesarean, and reflect on what felt positive and negative about her experience. Using consensus coding, three investigators independently evaluated the transcribed interviews, identifying recurring themes that were then discussed until consensus on the major themes was achieved. RESULTS: Four key themes emerged from patients' unplanned cesarean narratives: poor communication, fear of the operating room, distrust of the medical team, and loss of control. Lack of or incomplete trust in care providers was a new factor not previously recognized as a cause of distress or dissatisfaction in the literature to date. CONCLUSION: The four factors identified in this study are all potentially ameliorable, suggesting that changes in physician behavior may reduce patient dissatisfaction with unplanned cesarean birth. PMID- 27411935 TI - Effect of helmet liner systems and impact directions on severity of head injuries sustained in ballistic impacts: a finite element (FE) study. AB - The current study aims to investigate the effectiveness of two different designs of helmet interior cushion, (Helmet 1: strap-netting; Helmet 2: Oregon Aero foam padding), and the effect of the impact directions on the helmeted head during ballistic impact. Series of ballistic impact simulations (frontal, lateral, rear, and top) of a full-metal-jacketed bullet were performed on a validated finite element head model equipped with the two helmets, to assess the severity of head injuries sustained in ballistic impacts using both head kinematics and biomechanical metrics. Benchmarking with experimental ventricular and intracranial pressures showed that there is good agreement between the simulations and experiments. In terms of extracranial injuries, top impact had the highest skull stress, still without fracturing the skull. In regard to intracranial injuries, both the lateral and rear impacts generally gave the highest principal strains as well as highest shear strains, which exceed the injury thresholds. Off-cushion impacts were found to be at higher risk of intracranial injuries. The study also showed that the Oregon Aero foam pads helped to reduce impact forces. It also suggested that more padding inserts of smaller size may offer better protection. This provides some insights on future's helmet design against ballistic threats. PMID- 27411934 TI - Systematic review and meta-analysis of lactose digestion, its impact on intolerance and nutritional effects of dairy food restriction in inflammatory bowel diseases. AB - BACKGROUND: Relationships between inflammatory bowel disease and lactose containing foods remain controversial and poorly defined regarding symptoms, nutritional outcomes, and epidemiologic associations for lactose maldigestion. METHODS: A literature review was performed using Pub Med, Cochrane library and individual references, to extract data on lactose maldigestion prevalence in inflammatory bowel diseases. A meta-analysis was done using selected articles, to determine odds ratios of maldigestion. Information was collected about symptoms, impact on pattern of dairy food consumption, as well as the effects of dairy foods on the course of inflammatory bowel diseases. RESULTS: A total of 1022 articles were evaluated, 35 articles were retained and 5 studies were added from review articles. Of these 17 were included in meta-analysis which showed overall increased lactose maldigestion in both diseases. However increased risk on sub analysis was only found in Crohn's in patients with small bowel involvement. Nine additional studies were reviewed for symptoms, with variable outcomes due to confounding between lactose intolerance and lactose maldigestion. Fourteen studies were evaluated for dairy food effects. There was a suggestion that dairy foods may protect against inflammatory bowel disease. Nutritional consequences of dairy restrictions might impact adversely on bone and colonic complications. CONCLUSIONS: Lactose maldigestion in inflammatory bowel disease is dependent on ethnic makeup of the population and usually not disease. No bias of increased disease prevalence was noted between lactase genotypes. Intolerance symptoms depend on several parameters besides lactose maldigestion. Dairy foods may decrease risks of inflammatory bowel disease. Dairy restrictions may adversely affect disease outcome. PMID- 27411936 TI - Effect of prehospital epinephrine on out-of-hospital cardiac arrest: a report from the national out-of-hospital cardiac arrest data registry in Japan, 2011 2012. AB - PURPOSE: The effect of prehospital epinephrine on neurological outcome in out-of hospital cardiac arrest (OHCA) is still controversial. We sought to determine whether prehospital epinephrine administration was associated with improved outcomes in adult OHCA. METHODS: A nationwide, population-based, propensity score matched study of OHCA patients from January 1, 2011, to December 31, 2012, in Japan was conducted. We included adult OHCA patients treated by emergency medical service personnel without an excessive delay. The primary outcome was neurologically favorable survival 1 month after OHCA. RESULTS: A total of 237,068 patients (16,616 with a shockable rhythm and 220,452 with a non-shockable rhythm) were included in the final cohort. A total of 4024 out of the 16,616 shockable OHCAs and 29,393 out of the 220,452 non-shockable OHCAs received prehospital epinephrine. In the propensity score-matched cohort, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival (shockable OHCA 7.6 vs. 17.9 %, OR 0.38 [95%CI 0.33-0.43]; non-shockable OHCA 0.6 vs. 1.2 %, OR 0.47 [95%CI 0.39-0.56]). In the subgroup analyses, prehospital epinephrine was significantly associated with poor neurological outcome in all subgroups. In the ancillary analyses, although the neurological outcome was worse as the number of epinephrine doses increased or the time to epinephrine increased, patients had a greater chance of a favorable neurological outcome only when a single dose of epinephrine was administered within 15 min of the emergency call in shockable OHCA. CONCLUSIONS: Among adult OHCA patients, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival. Situations in which prehospital epinephrine is effective may be extremely limited. PMID- 27411937 TI - Changes in utilisation of antiepileptic drugs in epilepsy and non-epilepsy disorders-a pharmacoepidemiological study and clinical implications. AB - PURPOSE: The purpose of this study was to investigate changes in utilisation of antiepileptic drugs (AEDs) in epilepsy and non-epilepsy disorders in Norway and furthermore to study the retention rates of the most commonly used AEDs in these indications in long-term use. METHODS: The data consisted of all prescriptions of AEDs from Norwegian pharmacies in the Norwegian Prescription Database (NorPD) (2004-2012). Variables included anonymous data regarding age, gender, diagnosis specific reimbursement codes and utilisation of AEDs. RESULTS: In recent years (2008-2012), the utilisation of AEDs in non-epilepsy disorders accounted for 45 53 % of the total use. In epilepsy, the most commonly used AED was lamotrigine, followed by levetiracetam, carbamazepine and valproate. Lamotrigine was also the predominant AED used in psychiatry, while pregabalin and gabapentin were mostly used in neuropathic pain. In migraine, topiramate predominated but accounted for <1 % of the total utilisation of AEDs. The majority of prescriptions were by general practitioners and only 20 % by specialists. Regardless of indication, newer AEDs had higher retention rates (34-48 %) and were used for a longer period before discontinuation. CONCLUSIONS: The use of AEDs in non-epilepsy disorders is increasing and accounted for 53 % in 2012. Newer AEDs were predominantly used and demonstrated higher retention rates than older AEDs in all indications. This nationwide study demonstrates an increased exposure to AEDs in new patient groups, and details in prescription patterns and clinical and safety considerations should be closely monitored. This contributes to long-term post marketing data of AED and accordingly improved pharmacovigilance. PMID- 27411938 TI - Anaplasma, Ehrlichia and rickettsial pathogens in ixodid ticks infesting cattle and sheep in western Oromia, Ethiopia. AB - Although ticks are widely distributed in all agro-ecological zones of Ethiopia, information on tick-borne pathogens is scarce. This study was conducted to determine the presence of Anaplasma spp., Ehrlichia spp., and Rickettsia spp. in Rhipicephalus evertsi and Rhipicephalus (Boophilus) decoloratus collected from cattle and sheep at Bako, western Oromia, Ethiopia, using polymerase chain reaction and sequencing. Anaplasma ovis and Anaplasma spp., Ehrlichia ruminantium and Ehrlichia spp. were detected in Rh. decoloratus, whereas only A. ovis was detected in Rh. evertsi. Both tick species were found to harbor DNA belonging to Rickettsia spp., and Rickettsia africae. Our findings highlight the risk of infection of animals and humans with these zoonotic tick-borne bacteria in Ethiopia. PMID- 27411939 TI - Seasonal dynamics of ixodid ticks on wild rabbits Oryctolagus cuniculus (Leporidae) from Central Spain. AB - Rabbit Hemorrhagic Disease and Myxomatosis caused a decline in the rabbit population in the second half of the last century. Despite some recovery, the risk of vector-borne disease is present and thus the importance of controlling vector populations. In the current study, we describe the ixodid tick fauna in wild rabbit in a natural reserve in Ciudad Real (Central Spain) during the course of two 3-year periods (2007-2009 and 2012-2014). Of all the ticks collected on average 72.5 % were larvae, 24.4 % nymphs and 3.1 % adults, although the percentage varied monthly. Seven tick species were identified: Hyalomma lusitanicum Koch (Parasitic indicator [PI] = number of ticks per examined rabbit = 96.47), Rhipicephalus pusillus Gil Collado (PI = 47.37), Haemaphysalis hispanica Gil Collado (PI = 12.15), Ixodes ventalloi Gil Collado (PI = 0.65), R. bursa Canestrini and Fanzago (PI = 0.18), R. sanguineus Latreille (PI = 0.11), Dermacentor marginatus Sulzer (PI = 0.01). In spring and summer, most abundant were larvae of H. lusitanicum, followed by immature stages of R. pusillus and Ha. hispanica. In autumn, the main tick species were nymphs of I. ventalloi whereas in winter adults of Ha. hispanica were more numerous. Rhipicephalus pusillus was present all year long, although not always in high percentage. PI of other species (R. bursa, R. sanguineus and D. marginatus) were too low to be representative. The seasonal dynamics of ticks on wild rabbit defined in this study could be useful to design species-specific control strategies. PMID- 27411940 TI - Dominance status predicts social fear transmission in laboratory rats. AB - Acquiring information about stimuli that predict danger, through either direct experience or inference from a social context, is crucial for individuals' ability to generate appropriate behaviors in response to threats. Utilizing a modified demonstrator-observer paradigm (fear conditioning by proxy) that allows for free interaction between subjects, we show that social dominance hierarchy, and the interactive social behaviors of caged rats, is predictive of social fear transmission, with subordinate rats displaying increased fear responses after interacting with a fear-conditioned dominant rat during fear retrieval. Fear conditioning by proxy conserves some of the pathways necessary for direct fear learning (e.g., lateral amygdala) but is unique in that it requires regions necessary for emotional regulation (e.g., anterior cingulate cortex), making this paradigm an important tool for evaluating learning and behavior in the laboratory setting. PMID- 27411941 TI - Toxicity of hydroxylated polychlorinated biphenyls (HO-PCBs) using the bioluminescent assay Microtox((r)). AB - Hydroxylated polychlorinated biphenyls (HO-PCBs) are toxic contaminants which are produced in the environment by biological or abiotic oxidation of PCBs. The toxicity of a suite of 23 mono-hydroxylated derivatives of PCBs and 12 parent PCBs was determined using the bacterial bioluminescent assay Microtox((r)). All HO-PCBs tested exhibited higher toxicity than the corresponding parent PCB, with effect concentration 50 % (EC50) ranging from 0.07 to 133 mg L(-1). The highest toxicities were recorded with 4-hydroxylated derivatives of di-chlorinated biphenyls (EC50 = 0.07-0.36 mg L(-1)) and 2-hydroxylated derivatives of tri chlorinated biphenyls carrying a chlorine substituent on the phenolic ring (EC50 = 0.34-0.48 mg L(-1)). The toxicity of HO-PCBs generally decreased when the degree of chlorination increased. Consistently with this observation, a significant positive correlation was measured between toxicity (measured by EC50) and octanol-water partition coefficient (pK ow) for the HO-PCBs under study (Pearson's correlation coefficient, r = 0.74), which may be explained by the lower solubility and bioavailability generally associated with higher hydrophobicity. This study is the first one which assessed the toxicity of a suite of PCBs and HO-PCBs using the bioluminescent assay Microtox((r)), showing an inverse correlation between toxicity and hydrophobicity. PMID- 27411943 TI - Feasibility of extracting data from electronic medical records for research: an international comparative study. AB - BACKGROUND: Electronic medical records (EMR) offer a major potential for secondary use of data for research which can improve the safety, quality and efficiency of healthcare. They also enable the measurement of disease burden at the population level. However, the extent to which this is feasible in different countries is not well known. This study aimed to: 1) assess information governance procedures for extracting data from EMR in 16 countries; and 2) explore the extent of EMR adoption and the quality and consistency of EMR data in 7 countries, using management of diabetes type 2 patients as an exemplar. METHODS: We included 16 countries from Australia, Asia, the Middle East, and Europe to the Americas. We undertook a multi-method approach including both an online literature review and structured interviews with 59 stakeholders, including 25 physicians, 23 academics, 7 EMR providers, and 4 information commissioners. Data were analysed and synthesised thematically considering the most relevant issues. RESULTS: We found that procedures for information governance, levels of adoption and data quality varied across the countries studied. The required time and ease of obtaining approval also varies widely. While some countries seem ready for secondary uses of data from EMR, in other countries several barriers were found, including limited experience with using EMR data for research, lack of standard policies and procedures, bureaucracy, confidentiality, data security concerns, technical issues and costs. CONCLUSIONS: This is the first international comparative study to shed light on the feasibility of extracting EMR data across a number of countries. The study will inform future discussions and development of policies that aim to accelerate the adoption of EMR systems in high and middle income countries and seize the rich potential for secondary use of data arising from the use of EMR solutions. PMID- 27411942 TI - Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future. AB - The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing-thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl2.PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users. PMID- 27411944 TI - The effect of non-small cell lung cancer histology on survival as measured by the graded prognostic assessment in patients with brain metastases treated by hypofractionated stereotactic radiotherapy. AB - BACKGROUND: The purpose of this study was to investigate the impact of histology on survival stratified by the Graded Prognostic Assessment (GPA) for non-small cell lung cancer (NSCLC) in a group of selected patients treated recently. METHODS: A total of 171 NSCLC patients with brain metastases treated by hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy between 2001 and 2011 were included. The GPA score was calculated for each patient. Tumor histologies were categorized into adenocarcinoma (ADCA) and non-ADCA. Median survival time (MST, in months) was calculated using the Kaplan-Meier method. The log-rank test was used to determine statistical differences. RESULTS: MSTs by histology were: ADCA 15 (n = 92) and non-ADCA 10 (n = 79) (p < 0.001). For all patients, the MSTs by GPA score were: GPA 3.5-4, 24; GPA 2.5-3, 15; GPA 1.5-2, 9 and GPA 0-1, 6 (p < 0.001). The histology of ADCA showed a statistically significant higher MST than non-ADCA for patients with GPA 2.5-4. For GPA 2.5-3, MSTs were: ADCA 18, non-ADCA 10 (p = 0.007); for GPA 3.5-4, MSTs were: ADCA 30, non-ADCA 17 (p = 0.046). For GPA 0-2, MSTs did not differ significantly by histology. For GPA 0-1, MSTs were: ADCA 8, non-ADCA 4 (p = 0.146); GPA 1.5-2, MSTs were: ADCA 10, non-ADCA 8 (p = 0.291). We further found that non-ADCA in upper GPA class (3.5-4) had similar survival with ADCA in lower GPA class (2.5-3) (MSTs were 17 and 18, respectively, p = 0.775). This phenomenon also happened between patients of non-ADCA in upper GPA class (2.5-3) and those of ADCA in lower GPA class (1.5-2) (MSTs were both 10, p = 0.724). CONCLUSIONS: We confirmed that the histology of NSCLC had effect on the GPA in these selected patients treated recently. ADCA showed a statistically significant higher MST than non-ADCA with GPA 2.5-4. The non-ADCA in upper GPA classes (3.5-4 and 2.5-3) had similar survival to ADCA in lower GPA classes (2.5-3 and 1.5-2, respectively). The histology as a new factor should be added to the original GPA for NSCLC. PMID- 27411945 TI - The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography - a retrospective multicenter cohort study of 6543 primary breast cancer patients. AB - BACKGROUND: Mammography and ultrasound are the gold standard imaging techniques for preoperative assessment and for monitoring the efficacy of neoadjuvant chemotherapy in breast cancer. Maximum accuracy in predicting pathological tumor size non-invasively is critical for individualized therapy and surgical planning. We therefore aimed to assess the accuracy of tumor size measurement by ultrasound and mammography in a multicentered health services research study. METHODS: We retrospectively analyzed data from 6543 patients with unifocal, unilateral primary breast cancer. The maximum tumor diameter was measured by ultrasound and/or mammographic imaging. All measurements were compared to final tumor diameter determined by postoperative histopathological examination. We compared the precision of each imaging method across different patient subgroups as well as the method-specific accuracy in each patient subgroup. RESULTS: Overall, the correlation with histology was 0.61 for mammography and 0.60 for ultrasound. Both correlations were higher in pT2 cancers than in pT1 and pT3. Ultrasound as well as mammography revealed a significantly higher correlation with histology in invasive ductal compared to lobular cancers (p < 0.01). For invasive lobular cancers, the mammography showed better correlation with histology than ultrasound (p = 0.01), whereas there was no such advantage for invasive ductal cancers. Ultrasound was significantly superior for HR negative cancers (p < 0.001). HER2/neu positive cancers were also more precisely assessed by ultrasound (p < 0.001). The size of HER2/neu negative cancers could be more accurately predicted by mammography (p < 0.001). CONCLUSION: This multicentered health services research approach demonstrates that predicting tumor size by mammography and ultrasound provides accurate results. Biological tumor features do, however, affect the diagnostic precision. PMID- 27411946 TI - Boronate Affinity-Molecularly Imprinted Biocompatible Probe: An Alternative for Specific Glucose Monitoring. AB - A biocompatible probe for specific glucose recognition is based on photoinitiated boronate affinity-molecular imprinted polymers (BA-MIPs). The unique pre-self assembly between glucose and boronic acids creates glucose-specific memory cavities in the BA-MIPs coating. As a result, the binding constant toward glucose was enhanced by three orders of magnitude. The BA-MIPs probe was applied to glucose determination in serum and urine and implanted into plant tissues for low destructive and long-term in vivo continuous glucose monitoring. PMID- 27411947 TI - Reaction rate of a composite core-shell nanoreactor with multiple nanocatalysts. AB - We present a detailed theory for the total reaction rate constant of a composite core-shell nanoreactor, consisting of a central solid core surrounded by a hydrogel layer of variable thickness, where a given number of small catalytic nanoparticles are embedded at prescribed positions and are endowed with a prescribed surface reaction rate constant. Besides the precise geometry of the assembly, our theory accounts explicitly for the diffusion coefficients of the reactants in the hydrogel and in the bulk as well as for their transfer free energy jump upon entering the hydrogel shell. Moreover, we work out an approximate analytical formula for the overall rate constant, which is valid in the physically relevant range of geometrical and chemical parameters. We discuss in depth how the diffusion-controlled part of the rate depends on the essential variables, including the size of the central core. In particular, we derive some simple rules for estimating the number of nanocatalysts per nanoreactor for an efficient catalytic performance in the case of small to intermediate core sizes. Our theoretical treatment promises to provide a very useful and flexible tool for the design of superior performing nanoreactor geometries with optimized nanoparticle load. PMID- 27411948 TI - Maternal tobacco use and extremely premature birth - a population-based cohort study. AB - OBJECTIVE: To study the associations of maternal tobacco use (smoking or use of snuff) and risk of extremely preterm birth, and if tobacco cessation before antenatal booking influences this risk. To study the association between tobacco use and spontaneous or medically indicated onset of delivery. DESIGN: Population based cohort study. SETTING: Sweden. POPULATION: All live singleton births, registered in the Swedish Medical Birth Register, 1999-2012. METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis. MAIN OUTCOME MEASURES: Extremely preterm birth (<28 weeks of gestation), very preterm birth (28-31 weeks), moderately preterm birth (32-36 weeks). RESULTS: Maternal snuff use (OR 1.58; 95% CI: 1.14-2.21) and smoking (OR 1.61; 95% CI: 1.39-1.87 and OR 1.91; 95% CI: 1.53-2.39 for moderate and heavy smoking, respectively) were associated with an increased risk of extremely preterm birth. When cessation of tobacco use was obtained there was no increased risk of preterm birth. Snuff use was associated with a twofold risk increase of medically indicated extremely preterm birth, whereas smoking was associated with increased risks of both medically indicated and spontaneous extremely preterm birth. CONCLUSIONS: Snuff use and smoking in pregnancy were associated with increased risks of extremely preterm birth. Women who stopped using tobacco before the antenatal booking had no increased risk. These findings indicate that nicotine, the common substance in cigarettes and snuff, is involved in the mechanisms behind preterm birth. The use of nicotine should be minimized in pregnancy. TWEETABLE ABSTRACT: Tobacco use increases risk of extremely preterm birth. Cessation is preventive. Avoid nicotine in pregnancy. PMID- 27411949 TI - Biocompatible Silk Noil-Based Three-Dimensional Carded-Needled Nonwoven Scaffolds Guide the Engineering of Novel Skin Connective Tissue. AB - Retracting hypertrophic scars resulting from healed burn wounds heavily impact on the patients' life quality. Biomaterial scaffolds guiding burned-out skin regeneration could suppress or lessen scar retraction. Here we report a novel silk noil-based three-dimensional (3D) nonwoven scaffold produced by carding and needling with no formic acid exposure, which might improve burn healing. Once wetted, it displays human skin-like physical features and a high biocompatibility. Human keratinocyte-like cervical carcinoma C4-I cells seeded onto the carded-needled nonwovens in vitro quickly adhered to them, grew, and actively metabolized glutamine releasing lactate. As on plastic, they released no proinflammatory IL-1beta, although secreting tumor necrosis factor-alpha, an inducer of the autocrine mitogen amphiregulin in such cells. Once grafted into interscapular subcutaneous tissue of mice, carded-needled nonwovens guided the afresh assembly of a connective tissue enveloping the fibroin microfibers and filling the interposed voids within 3 months. Fibroblasts and a few poly- or mononucleated macrophages populated the engineered tissue. Besides, its extracellular matrix contained thin sparse collagen fibrils and a newly formed vascular network whose endothelin-1-expressing endothelial cells grew first on the fibroin microfibrils and later expanded into the intervening matrix. Remarkably, no infiltrates of inflammatory leukocytes and no packed collagen fibers bundles among fibroin microfibers, no fibrous capsules at the grafts periphery, and hence no foreign body response was obtained at the end of 3 months of observation. Therefore, we posit that silk noil-based 3D carded-needled nonwoven scaffolds are tools for translational medicine studies as they could guide connective tissue regeneration at deep burn wounds averting scar retraction with good functional results. PMID- 27411950 TI - Directing lineage specification of human mesenchymal stem cells by decoupling electrical stimulation and physical patterning on unmodified graphene. AB - The organization and composition of the extracellular matrix (ECM) have been shown to impact the propagation of electrical signals in multiple tissue types. To date, many studies with electroactive biomaterial substrates have relied upon passive electrical stimulation of the ionic media to affect cell behavior. However, development of cell culture systems in which stimulation can be directly applied to the material - thereby isolating the signal to the cell-material interface and cell-cell contracts - would provide a more physiologically-relevant paradigm for investigating how electrical cues modulate lineage-specific stem cell differentiation. In the present study, we have employed unmodified, directly stimulated, (un)patterned graphene as a cell culture substrate to investigate how extrinsic electrical cycling influences the differentiation of naive human mesenchymal stem cells (hMSCs) without the bias of exogenous biochemicals. We first demonstrated that cyclic stimulation does not deteriorate the cell culture media or result in cytotoxic pH, which are critical experiments for correct interpretation of changes in cell behavior. We then measured how the expression of osteogenic and neurogenic lineage-specific markers were altered simply by exposure to electrical stimulation and/or physical patterns. Expression of the early osteogenic transcription factor RUNX2 was increased by electrical stimulation on all graphene substrates, but the mature marker osteopontin was only modulated when stimulation was combined with physical patterns. In contrast, the expression of the neurogenic markers MAP2 and beta3-tubulin were enhanced in all electrical stimulation conditions, and were less responsive to the presence of patterns. These data indicate that specific combinations of non-biological inputs - material type, electrical stimulation, physical patterns - can regulate hMSC lineage specification. This study represents a substantial step in understanding how the interplay of electrophysical stimuli regulate stem cell behavior and helps to clarify the potential for graphene substrates in tissue engineering applications. PMID- 27411951 TI - N-terminal pro b-type natriuretic peptide (NT-pro-BNP) -based score can predict in-hospital mortality in patients with heart failure. AB - Serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) testing is recommended in the patients with heart failure (HF). We hypothesized that NT-pro BNP, in combination with other clinical factors in terms of a novel NT-pro BNP based score, may provide even better predictive power for in-hospital mortality among patients with HF. A retrospective study enrolled adult patients with hospitalization-requiring HF who fulfilled the predefined criteria during the period from January 2011 to December 2013. We proposed a novel scoring system consisting of several independent predictors including NT-pro-BNP for predicting in-hospital mortality, and then compared the prognosis-predictive power of the novel NT-pro BNP-based score with other prognosis-predictive scores. A total of 269 patients were enrolled in the current study. Factors such as "serum NT-pro BNP level above 8100 mg/dl," "age above 79 years," "without taking angiotensin converting enzyme inhibitors/angiotensin receptor blocker," "without taking beta blocker," "without taking loop diuretics," "with mechanical ventilator support," "with non-invasive ventilator support," "with vasopressors use," and "experience of cardio-pulmonary resuscitation" were found as independent predictors. A novel NT-pro BNP-based score composed of these risk factors was proposed with excellent predictability for in-hospital mortality. The proposed novel NT-pro BNP-based score was extremely effective in predicting in-hospital mortality in HF patients. PMID- 27411952 TI - Rhetoric or reality? What nurse practitioners do to provide self-management support in outpatient clinics: an ethnographic study. AB - AIMS AND OBJECTIVES: To describe how nurse practitioners enact their role in outpatient consultations, and how this compares to their perception of their responsibility for patients with chronic conditions. BACKGROUND: Nurse practitioners working with patients with chronic conditions seek to support them in self-managing their diseases. DESIGN: An ethnographic study. METHODS: Episodic participant observations (in total 48 hours) were carried out combined with formal interviews. The study population consisted of a purposive sample of nurse practitioners working in five outpatient clinics related to chronic care in one university medical centre in the Netherlands. Two different types of clinics were selected, namely (1) for patients with episodic flare-ups and (2) for patients with diseases requiring life-saving procedures. RESULTS: The nurse practitioners perceived the monitoring of patients' treatment as their main professional responsibility. Four monitoring strategies could be distinguished: 'assessing health conditions', 'connecting with patients', 'prioritising treatment in daily living' and 'educating patients'. CONCLUSION: While nurse practitioners considered building a relationship with their patients of utmost importance, their consultations were mostly based on a conventional medical model of medical history taking. Little attention was paid to the social, psychological and behavioural dimensions of illness. Nurse practitioners in this study seemed quite successful in their extension into medical territory, but moving patients' illness perceptions to the background was not conducive to self-management support. RELEVANCE TO CLINICAL PRACTICE: By their medical subspecialty expertise, nurse practitioners have a major role in the longitudinal process of the management of chronic diseases' treatment. Supporting patients to reduce the impact of the disease and its complications requires nurse practitioners to develop new coaching strategies designed to meet patients' individual needs. PMID- 27411953 TI - Production and stability of mechanochemically exfoliated graphene in water and culture media. AB - The preparation of graphene suspensions in water, without detergents or any other additives is achieved using freeze-dried graphene powders, produced by mechanochemical exfoliation of graphite. These powders of graphene can be safely stored or shipped, and promptly dissolved in aqueous media. The suspensions are relatively stable in terms of time, with a maximum loss of ~25% of the initial concentration at 2 h. This work provides an easy and general access to aqueous graphene suspensions of chemically non-modified graphene samples, an otherwise (almost) impossible task to achieve by other means. A detailed study of the stability of the relative dispersions is also reported. PMID- 27411954 TI - The interaction of protein-coated bionanoparticles and surface receptors reevaluated: how important is the number of bonds? AB - Specifically designed bionanoparticles with a function-oriented protein-coating layer interact with self-prepared receptor surfaces as the counterpart. Based on surface plasmon resonance biosensing experiments, a model framework is validated to estimate the number of bonds formed between these bionanoparticles and the receptor surface based on multivalent interactions. Our multi-site kinetic model is able to analyze the adsorption rate constants and the number of bonds from experimental data of natural and synthetic bionanoparticles. The influence of the mass transport on the adsorption kinetics is modeled including a diffusional boundary layer where a helpful analytical solution has been derived. Our model framework extends previous studies to include a higher number of bonds, ranging from 1 up to 1000. An almost linear relationship between the number of bonds and the adsorption amount of bionanoparticles makes the model framework suitable to predict, for example, ligand density and to further assess coating performance. The proposed model framework can serve as a design tool for multivalent interaction experiments under variable process conditions. PMID- 27411956 TI - Why still marry? The role of feelings in the persistence of marriage as an institution(1). AB - Despite cohabitation becoming increasingly equivalent to marriage in some of the most 'advanced' Western European societies, the vast majority of people still marry. Why so? Existing theories, mostly based on various approaches tied to cognitive decision-making, do not provide a sufficient explanation of the persistence of marriage. In this article, we argue that feelings attached to marriage, i.e. the affective evaluation of those involved in a partner relationship concerning marriage as opposed to cohabitation, explain the persistent importance of marriage as an institution. We argue that socialization, biological and social-structural factors affect these affective evaluations. We provide a test of our hypotheses using a longitudinal study of young adults in the Netherlands. The results of our analyses are consistent with a central role of feelings in the decision to marry, as well as with a role for key moderating factors such as gender. PMID- 27411955 TI - Structural basis of transcobalamin recognition by human CD320 receptor. AB - Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320DeltaE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320DeltaE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway. PMID- 27411957 TI - A New Generation of Smart Amine Donors for Transaminase-Mediated Biotransformations. AB - The application of omega-transaminase biocatalysts for the synthesis of optically pure chiral amines presents a number of challenges, including difficulties associated with displacing the challenging reaction equilibria. Herein, we report a highly effective approach using low equivalents of the new diamine donor, cadaverine, which enables high conversions of challenging substrates to the corresponding chiral amines in excellent ee. This approach paves the way for the design of self-sufficient fermentation processes combining transaminase biotransformations with existing strategies for cadaverine production by decarboxylation of endogenous lysine. PMID- 27411959 TI - Experimental and molecular dynamics studies of anthraquinone dyes in a nematic liquid-crystal host: a rationale for observed alignment trends. AB - Five anthraquinone dyes with bis(4-propylphenyl) substituents, connected via sulfide or amine linking groups at the 1,5-positions or directly at the 2,6 positions, have been studied as guests in the nematic liquid crystal host, E7. Polarized UV-visible absorption spectra of aligned samples were used to obtain experimental dichroic order parameters, which exhibit values in the range 0.51 0.74. Fully atomistic MD simulations of these guest-host systems were carried out, generally using default parameters but using new force constants derived here for the dyes containing flexible phenyl-sulfide and phenyl-amine linking groups. An analysis of the alignment of the dye molecules in these simulations provides calculated molecular order parameters, which are combined with calculated order parameters for the alignment of the transition dipole moments within the dyes, reported previously, to give calculated dichroic order parameters. The trend in the calculated dichroic order parameters between the dyes shows a good match with the trend in the experimental values, enabling the observed variation to be rationalised primarily by changes in the alignment of the calculated transition dipole moments within the dyes; the calculated molecular order parameters show a relatively small variation between the dyes. The results indicate that this computational approach may be used generally to rationalise trends in the alignment of guest molecules in liquid crystal hosts, suggesting that it may also be able to provide a predictive aid in the design of guest dyes. PMID- 27411960 TI - Effect of estradiol cypionate and GnRH treatment on plasma estradiol-17beta concentrations, synchronization of ovulation and on pregnancy rates in suckled beef cows treated with FTAI-based protocols. AB - Two experiments were conducted to evaluate the effect of different ovulation inducers on E-17beta plasma concentrations, synchronized ovulations and pregnancy rates. In Experiment 1, cows received a progesterone intravaginal device (PID) with 1 g of progesterone (P4) plus 2 mg of estradiol benzoate (EB) (day 0). At PID removal (day 8), cows received 0.150 mg of D-cloprostenol and were randomly assigned to four treatment groups (n = 10/treatment): Group ECP: 1 mg of estradiol cypionate at PID removal, Group EB: 1 mg of EB 24 hr after PID removal, Group GnRH: 10 MUg of GnRH 48 hr after PID removal, Group ECP-GnRH: 1 mg of ECP at PID removal plus 10 MUg of GnRH 48 hr later. Ultrasonographic examinations were performed to detect the dominant follicle and ovulation. GnRH-treated cows ovulated later (p < .05) compared to ECP- and ECP+GnRH-treated cows. There were effects of treatment, time and their interaction on E-17beta concentrations (p < .05). ECP treatment affected plasma E-17beta concentration, which increased earlier and decreased later compared to treatments without ECP. In Experiment 2, cows received (i) ECP: n = 126; (ii) EB: n = 126; (iii) GnRH: n = 136; (iv) ECP+GnRH: n = 139; FTAI was performed 48-50 hr after PID removal. Pregnancy rates did not differ among ovulation inducers (p > .05; ECP: 54.0%, 68/126; EB: 49.2%, 62/126; GnRH: 40.4%, 55/136; ECP+GnRH: 43.9%, 61/139). In conclusion, ECP administration (ECP and ECP+GnRH treatments) affected E-17beta concentrations, determining its earlier increase and later decrease compared to treatments without ECP (EB and GnRH treatments). ECP+GnRH-treated cows achieved the best distribution of ovulations without affecting pregnancy rates. PMID- 27411958 TI - IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin. AB - B cells participate in immune surveillance in human circulation and tissues, including tumors such as melanoma. By contrast, the role of humoral responses in cutaneous immunity is underappreciated. We report circulating skin-homing CD22+CLA+B cells in healthy volunteers and melanoma patients (n = 73) and CD22+ cells in melanoma and normal skin samples (n = 189). Normal and malignant skin featured mature IgG and CD22 mRNA, alongside mRNA for the transiently-expressed enzyme Activation-induced cytidine Deaminase (AID). Gene expression analyses of publically-available data (n = 234 GEO, n = 384 TCGA) confirmed heightened humoral responses (CD20, CD22, AID) in melanoma. Analyses of 51 melanoma associated and 29 normal skin-derived IgG sequence repertoires revealed lower IgG1/IgGtotal representation compared with antibodies from circulating B cells. Consistent with AID, comparable somatic hypermutation frequencies and class switching indicated affinity-matured antibodies in normal and malignant skin. A melanoma-associated antibody subset featured shorter complementarity-determining (CDR3) regions relative to those from circulating B cells. Clonal amplification in melanoma-associated antibodies and homology modeling indicated differential potential antigen recognition profiles between normal skin and melanoma sequences, suggesting distinct antibody repertoires. Evidence for IgG-expressing B cells, class switching and antibody maturation in normal and malignant skin and clonally-expanded antibodies in melanoma, support the involvement of mature B cells in cutaneous immunity. PMID- 27411962 TI - Genetic differences among Haplorchis taichui populations in Indochina revealed by mitochondrial COX1 sequences. AB - Haplorchis taichui is an intestinal heterophyid fluke that is pathogenic to humans. It is widely distributed in Asia, with a particularly high prevalence in Indochina. Previous work revealed that the lack of gene flow between three distinct populations of Vietnamese H. taichui can be attributed to their geographic isolation with no interconnected river basins. To test the hypothesis that interconnected river basins allow gene flow between otherwise isolated populations of H. taichui, as previously demonstrated for another trematode, Opisthorchis viverrini, we compared the genetic structures of seven populations of H. taichui from various localities in the lower Mekong Basin, in Thailand and Laos, with those in Vietnam, using the mitochondrial cytochrome c oxidase subunit 1 (COX1) gene. To determine the gene flow between these H. taichui populations, we calculated their phylogenetic relationships, genetic distances and haplotype diversity. Each population showed very low nucleotide diversity at this locus. However, high levels of genetic differentiation between the populations indicated very little gene flow. A phylogenetic analysis divided the populations into four clusters that correlated with the country of origin. The negligible gene flow between the Thai and Laos populations, despite sharing the Mekong Basin, caused us to reject our hypothesis. Our data suggest that the distribution of H. taichui populations was incidentally associated with national borders. PMID- 27411963 TI - Interplay of genetic and epigenetic alterations in hepatocellular carcinoma. AB - Genetic and epigenetic alterations play prominent roles in hepatocarcinogenesis and their appearance varies depending on etiological factors, race and tumor progression. Intriguingly, distinct patterns of these genetic and epigenetic mutations are coupled not only to affect each other, but to trigger different types of tumorigenesis. The patterns and frequencies of somatic variations vary depending on the nature of the surrounding chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutation. Therefore, genetic mutations and epigenetic alterations in hepatocellular carcinoma appear to be inseparable factors that accelerate tumorigenesis synergistically. We have summarized recent findings on genetic and epigenetic modifications, their influences on each other's alterations and putative roles in liver tumorigenesis. PMID- 27411964 TI - Inhibition of MiR-92a May Protect Endothelial Cells After Acute Myocardial Infarction in Rats: Role of KLF2/4. AB - BACKGROUND This study was designed to investigate the effects of microRNA-92 (miR 92), Kruppel-like factor 2 (KLF2), and Kruppel-like factor 4 (KLF4) on endothelial injury after acute myocardial infarction (AMI). MATERIAL AND METHODS Blood samples were collected from 50 AMI patients for detection of cardiac troponin I (cTnI), heart-type fatty acid-binding protein (H-FABP), and von Willebrand factor (vWF). The Sprague-Dawley rat models of AMI (n=30) were established by ligating their left anterior descending coronary artery. The cardiac markers of AMI patients and rat models were analyzed with enzyme-linked immunosorbent assay and immunohistochemistry. Human umbilical vein endothelial cells were processed into 5 groups: control, negative control, miR-92a inhibitors, miR-92a inhibitors + KLF2 small interfering RNA (siRNA), and miR-92a inhibitors + KLF4 siRNA. Cell proliferation and apoptosis were detected using MTT assay and flow cytometry. RT-PCR and Western blot were conducted to analyze KLF2 and KLF4 expressions. RESULTS AMI patients exhibited significantly higher expression of both endothelial injury markers (e.g., cTnI, H-FABP, vWF) and miR 92a in blood samples, when compared with controls (P<0.05). Model rats also had similar expressional tendencies, along with lower KLF2 and KLF4 expressions (P<0.05). Further, it could be observed in cellular experiments that treatment of miR-92a mimics can further upregulate endothelial injury markers, and miR-92a and both KLF2 and KLF4 were downregulated by miR-92a mimics (all, P<0.05). Also, the luciferase activity assay confirmed the direct binding of miR-92a to 3' UTR of KLF2/4. CONCLUSIONS MiR-92a was involved in the endothelial injury process after AMI and was able to suppress KLF2 and KLF4 expression. PMID- 27411965 TI - Effectiveness of interventions for adult peripheral intravenous catheterization: A systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Peripheral intravenous catheterization (PIVC) is commonly performed on emergency departments and inpatient units. Unsuccessful PIVC first attempts increase pain, and lead to treatment and diagnostic delays. OBJECTIVE: To determine strategies associated with PIVC first attempt success in adult emergency department patients and inpatients. METHODS: We searched MEDLINE, EMBASE, CINAHL, TRIP, Cochrane Central Register of Controlled Trials (OVID), and grey literatures databases such as Proquest Dissertation and Theses Global, and Open Grey databases between November and December, 2014. The search was updated on January 28, 2016. We included full text reports of randomized controlled trials testing PIVC interventions versus standard of care. Risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: We included 14 randomized controlled trials involving 3201 participants. Interventions included the AccuVeinTM, AccuCathTM catheter system, ultrasound, safety catheters, and topical anesthetics. Three studies compared AutoGuard and Insyte catheters and were suitable for meta-analysis. There was no difference in first attempt success with a relative risk of 0.0 (95% CI, -0.04, 0.04). There was limited evidence to support the use of ultrasound to increase first attempt success. CONCLUSIONS: Well-designed and reported randomized controlled trials examining the effectiveness of ultrasound compared to standard of care are warranted. REGISTRATION: PROSPERO registration: CRD42014015428. PMID- 27411966 TI - Quantitative Persulfide Site Identification (qPerS-SID) Reveals Protein Targets of H2S Releasing Donors in Mammalian Cells. AB - H2S is an important signalling molecule involved in diverse biological processes. It mediates the formation of cysteine persulfides (R-S-SH), which affect the activity of target proteins. Like thiols, persulfides show reactivity towards electrophiles and behave similarly to other cysteine modifications in a biotin switch assay. In this manuscript, we report on qPerS-SID a mass spectrometry based method allowing the isolation of persulfide containing peptides in the mammalian proteome. With this method, we demonstrated that H2S donors differ in their efficacy to induce persulfides in HEK293 cells. Furthermore, data analysis revealed that persulfide formation affects all subcellular compartments and various cellular processes. Negatively charged amino acids appeared more frequently adjacent to cysteines forming persulfides. We confirmed our proteomic data using pyruvate kinase M2 as a model protein and showed that several cysteine residues are prone to persulfide formation finally leading to its inactivation. Taken together, the site-specific identification of persulfides on a proteome scale can help to identify target proteins involved in H2S signalling and enlightens the biology of H2S and its releasing agents. PMID- 27411967 TI - Template-assisted colloidal self-assembly of macroscopic magnetic metasurfaces. AB - We demonstrate a template-assisted colloidal self-assembly approach for magnetic metasurfaces on macroscopic areas. The choice of anisotropic colloidal particle geometry, assembly pattern and metallic film is based on rational design criteria, taking advantage of mirror-charge effects for gold nanorods placed on gold film. Monodisperse gold nanorods prepared utilizing wet-chemistry are arranged with high precision on wrinkled templates to form linear array-type assemblies and subsequently transferred to a thin gold film. Due to the obtained particle-to-film distance of 1.1 nm, the plasmonic mode of the nanorod is able to couple efficiently with the supporting metallic film, giving rise to a magnetic mode in the visible spectrum (721 nm). Conventional UV-vis-NIR measurements in close correlation with electromagnetic simulations provide evidence for the presence of a magnetic resonance on the macroscopic area. The herein presented scalable lithography-free fabrication process paves the road towards colloidal functional metasurfaces with an optical response in the effective magnetic permeability. PMID- 27411968 TI - Effects of mannan level and beta-mannanase supplementation on growth performance, apparent total tract digestibility and blood metabolites of growing pigs. AB - The exogenous enzymes are less consistent in their effects as their beneficial effects depend upon the types and level non-starch polysaccharides (NSP) present in the diets. Therefore, exogenous enzymes should be selected on the basis of types and amount of the NSP in the pig diets. The objectives of the present experiments were to investigate the effects of dietary level of mannan and beta mannanase supplementation on growth performance, apparent total tract digestibility (ATTD) of energy and nutrients, and blood metabolites of growing pigs. In Exp. 1, 96 barrows were randomly allotted to four treatments on the basis of BW. There were four replicates in each treatment with six pigs per replicate. The dietary treatments were a corn-soybean meal (SBM)-based control diet and three other diets consisted of the control diet supplemented with 400, 800 or 1600 U of beta-mannanase/kg diet. The final BW, average daily gain (ADG) and blood glucose increased (linear, P0.05) on the concentrations of blood total cholesterol, triacylglycerides and blood urea nitrogen. These results indicate that supplementation of beta-mannanase to low- or high-mannan diets have potential to improve the performance of growing pigs. In addition, palm kernel meal may partially replace corn and SBM without reducing pig performance if beta mannanase is added to diet. PMID- 27411969 TI - Effects of naltrexone on alcohol self-administration and craving: meta-analysis of human laboratory studies. AB - Randomized clinical trials have established the efficacy of naltrexone for reducing quantity of alcohol consumption and incidence of relapse to heavy drinking. To evaluate putative treatment mechanisms, human laboratory studies have examined naltrexone's effects on alcohol responses and self-administration during short-term medication protocols. Results from these studies are inconsistent and have yet to be examined in aggregate. This meta-analysis aimed to quantify naltrexone's effects on alcohol self-administration and craving in the context of placebo-controlled human laboratory trials. Potential moderators of medication effects were also examined. Meta-analyses of alcohol self administration (k = 9, N = 490) and craving (k = 16, N = 748) confirmed that, under controlled experimental conditions, naltrexone reduces the quantity of consumption (Hedges' g = -.277, SE = .074, 95 percent CI = -.421, -.133, p < .001) and magnitude of self-reported craving (g = -.286, SE = .066, 95 percent CI = -.416, -.156, p < .001) relative to placebo. Subgroup and moderation analyses found no evidence that effect sizes differed by study population (dependent versus non-dependent drinkers), laboratory paradigm or duration of medication exposure. These results substantiate prior evidence for reductions in event-level craving and consumption as potential treatment mediators, also establishing effect sizes to inform future human laboratory trials. From a clinical perspective, these results may provide additional evidence regarding naltrexone's efficacy in the context of acute or subacute dosing regimens. PMID- 27411970 TI - Physiologic monitor alarms for children: Pushing the limits. PMID- 27411971 TI - Hybrid Cluster Precursors of the LaZrO Insulator for Transistors: Properties of High-Temperature-Processed Films and Structures of Solutions, Gels, and Solids. AB - In the solution processing of oxide electronics, the structure of metal-organic precursors in solution and their effect on processability and on the final structure and properties of the oxide have rarely been studied. We have observed that hybrid clusters, having inorganic cores coordinated by organic ligands, are the typical form of metal-organic precursor structures. For insulating ternary LaZrO, improved synthesis of the cluster precursor under solvothermal conditions led to low-temperature deposition of the film at 200 degrees C, as we will report in another paper. In the current paper, we first briefly show that solvothermal synthesis of the precursor resulted in significantly improved insulating properties (e.g., two orders lower leakage current) of high temperature-annealed films, and then focus on the structural analysis of the cluster precursors and annealed solids and relate the results to the significant improvement of properties by solvothermal treatment of solutions. A change in the cluster core toward structural unification was brought about by solvothermal treatment, resulting in higher uniformity and higher stability of clusters. The final structure of the material maintained the features of the core structure in solution, even after annealing at high temperatures. These results demonstrate the key role played by designing cluster structure in solution. PMID- 27411972 TI - Development of a biomimetic microfluidic oxygen transfer device. AB - Blood oxygenators provide crucial life support for patients suffering from respiratory failure, but their use is severely limited by the complex nature of the blood circuit and by complications including bleeding and clotting. We have fabricated and tested a multilayer microfluidic blood oxygenation prototype designed to have a lower blood prime volume and improved blood circulation relative to current hollow fiber cartridge oxygenators. Here we address processes for scaling the device toward clinically relevant oxygen transfer rates while maintaining a low prime volume of blood in the device, which is required for clinical applications in cardiopulmonary support and ultimately for chronic use. Approaches for scaling the device toward clinically relevant gas transfer rates, both by expanding the active surface area of the network of blood microchannels in a planar layer and by increasing the number of microfluidic layers stacked together in a three-dimensional device are addressed. In addition to reducing prime volume and enhancing gas transfer efficiency, the geometric properties of the microchannel networks are designed to increase device safety by providing a biomimetic and physiologically realistic flow path for the blood. Safety and hemocompatibility are also influenced by blood-surface interactions within the device. In order to further enhance device safety and hemocompatibility, we have demonstrated successful coating of the blood flow pathways with human endothelial cells, in order to confer the ability of the endothelium to inhibit coagulation and thrombus formation. Blood testing results provide confirmation of fibrin clot formation in non-endothelialized devices, while negligible clot formation was documented in cell-coated devices. Gas transfer testing demonstrates that the endothelial lining does not reduce the transfer efficiency relative to acellular devices. This process of scaling the microfluidic architecture and utilizing autologous cells to line the channels and mitigate coagulation represents a promising avenue for therapy for patients suffering from a range of acute and chronic lung diseases. PMID- 27411973 TI - Multimodality assessment of upper airway obstruction in children with persistent obstructive sleep apnea after adenotonsillectomy. AB - OBJECTIVES/HYPOTHESIS: Children with obstructive sleep apnea (OSA) may have multiple sites of upper airway obstruction (UAO). A wide variety of techniques has been used to evaluate UAO. Our aim was to compare findings of cine magnetic resonance imaging (MRI) and drug-induced sleep endoscopy (DISE) in identifying UAO sites in children with persistent OSA after adenotonsillectomy (AT). STUDY DESIGN: Retrospective chart review. MATERIAL AND METHODS: The medical records of children who underwent DISE and cine MRI were reviewed. Data pertaining to demographics, past medical history, body mass index, polysomnography, findings of DISE, and cine MRI were obtained. RESULTS: Fifteen children (11 boys, 4 girls; age range, 7-18 years) were identified. Comorbid conditions were Down syndrome in nine patients, cerebral palsy in one, attention deficit hyperactivity disorder in two, and asthma in three. Severity of OSA was moderate in five, and severe in 10. DISE and cine MRI showed the same UAO site in 10 patients: a single site (tongue) in nine and multiple sites (tongue and oropharynx/lateral walls) in one. DISE showed additional UAO sites undetected by cine MRI in three patients. Cine MRI showed additional UAO sites undetected by DISE in one patient. DISE and cine MRI showed different sites of obstruction in one patient. CONCLUSIONS: Cine MRI and DISE documented single and multiple sites of UAO in children with persistent OSA after AT. Cine MRI and DISE findings were similar in the majority of the children. Assessment of the sensitivity and specificity of cine MRI and DISE in detecting sites of UAO merits further investigation. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1224-1230, 2017. PMID- 27411974 TI - An Intervention to Enhance Psychological Capital and Health Outcomes in Homeless Female Youths. AB - Female homeless youths are vulnerable to risky sex and substance use behaviors, yet they have strengths known as psychological capital. A quasi-experimental pre post research design with repeated measures was used to examine the feasibility and preliminary efficacy of a brief intervention to enhance psychological capital, reduce health-risk behaviors, and achieve short-term behavioral goals. Study participants were 80 ethnically diverse homeless women between the ages of 18 and 23 years. Intervention participants had significant improvements in psychological capital, hope, resilience, and self-efficacy to refuse alcohol, social connectedness, and substance use ( p < .05). There was a significant group by time interaction for safe sex self-efficacy; intervention participants had greater self-confidence in negotiating safer sex practices than comparison participants. At the follow-up post-test, 82% of intervention participants who remained in the study had met or exceeded their short-term goals. This brief, street-based intervention was feasible and showed preliminary efficacy. PMID- 27411975 TI - Dementia Caregiver Grief and Bereavement: An Integrative Review. AB - Alzheimer's disease and related dementias make up the fifth leading cause of death for individuals of 65 years of age and older in the United States. Seventy percent of these individuals will die in long-term care settings. The aim of this integrative review was to examine and synthesize the evidence on grief and bereavement in Alzheimer's disease and related dementias caregivers. This review identified five critical gaps in the existing evidence: (a) a lack of ethnic and gender diversity among caregivers studied, (b) limited use of valid instruments to study dementia caregiver grief and bereavement, PMID- 27411976 TI - Identifying the Structure and Effect of Drinking-Related Self-Schemas. AB - Self-schemas have received increased attention as favorable targets for therapeutic intervention because of their central role in self-perception and behavior. The purpose of this integrative review was to identify, evaluate, and synthesize existing research pertaining to drinking-related self-schemas. Russell's integrative review strategy guided the search. Sixteen published works were identified, meeting criteria for evaluation ( n = 12 data-based publications and n = 4 models). The retrieved data-based publications rated fair-good using Polit and Beck's criteria; the overall body of literature rated "B" using Grimes and Schulz criteria. Retrieved models rated 4 to 7 using Fitzpatrick and Whall's criteria. The existing literature strongly supports the availability of a drinking-related self-schema among moderate-to-heavy drinking samples, and suggests a positive relationship between elaboration and drinking behavior. The relationship between valenced content of the schema and drinking behavior remains unexplored. Identifying variation in the structural properties of drinking related self-schemas could lay the foundation for future interventions. PMID- 27411977 TI - Depressive Symptoms: Mediator of Event-Free Survival in Patients With Heart Failure. AB - Depressive symptoms and poor health perceptions are predictors of higher hospitalization and mortality rates (heart failure [HF]). However, the association between depressive symptoms and health perceptions as they affect event-free survival outcomes in patients with HF has not been studied. The purpose of this secondary analysis was to determine whether depressive symptoms mediate the relationship between health perceptions and event-free survival in patients with HF. A total of 458 HF patients (61.6 +/- 12 years, 55% New York Heart Association Class III/IV) responded to one-item health perception question and completed the Patient Health Questionnaire-9. Event-free survival data were collected for up to 4 years. Multiple regression and Cox proportional hazards regression analysis showed that depressive symptoms mediated the relationship between health perceptions and event-free survival. Decreasing depressive symptoms is essential to improve event-free survival in patients with HF. PMID- 27411979 TI - Grazing-induced Synechococcus microcolony formation: experimental insights from two freshwater phylotypes. AB - Freshwater cyanobacteria of the genus Synechococcus are ubiquitous and organized either as single cells of diverse morphology or as microcolonies of different size. We studied the formation of microcolonies induced by the mixotrophic nanoflagellate Poterioochromonas sp. grazing on two Synechococcus strains belonging to phylotypes with different content of phycobiliproteins (PE: phycoerythrin-rich cells, L.Albano Group A; PC: phycocyanin-rich cells, MW101C3 Group I). The quantitative variations in cell abundance, morphological and physiological conditions were assessed on short-term incubations in semi continuous cultures, single culture (PE, PC) and co-culture (PE+PC), with and without predators, by flow cytometry, and PhytoPAM. Under grazing pressure, we observed that (i) the abundance of PE single cells decreased over time with a concomitant formation of PE microcolonies; (ii) in PC single cultures, no significant variation in single cells was found and microcolonies did not form; (iii) both PE and PC formed monoclonal microcolonies in co-culture; (iv) PC cells increased the photosynthetic efficiency of the PSII (higher Fv/Fm) in co-culture. In the aftermath of microcolony formation as a predation-induced adaptation, our findings indicated a different response of Synechococcus phylotypes potentially co-existing in natural environment and the importance of their interaction. PMID- 27411978 TI - One-pot polyglycidol nanogels via liposome master templates for dual drug delivery. AB - Polyglycidol-based nanohydrogels (nHGs) have been prepared by optimizing the use of liposome master templates resulting in a high-yielding and more practical one pot process to provide materials capable of carrying drugs of adverse chemical nature. The nanogels prepared with the one-pot method showed favorable kinetics for the release of either Nile Red (NR) or lysozyme (LYS), loaded with gel precursors such as semi-branched poly(glycidol allylglycidyl ether), PEG dithiol (1KDa), a free radical initiator and liposomal lipids at the liposome formation step. This process is superior to a comparable step-wise traditional approach and circumvents loading of the gel precursors with the hydrophilic drug into preformed liposome templates. A thiol-ene crosslinking reaction accomplishes the formation of the nanonetwork resulting in nHGs prepared in the traditional step wise (nHG-SW) approach and the one-pot (nHG-OP) process. Both nanogel networks were characterized in terms of particle size and zeta (zeta) potential with average values of 148nm+/-39nm and -25.9mV+/-9.2 for the nHG-SW and 132nm+/-32 and -23.1mV+/-9.7 for the nHG-OPs. Loading efficiency for both of the nanogels with NR was determined by spectrophotometry to be 28% (nHP-SW) and 31% (nHP-OP). The LYS loading was based on the target loading of 10MUg/mg for both nanogels found to be 84% and 86% for the nHG-SW and nHP-OP, respectively. As proof of concept for combination drug delivery, the in vitro release of both drug mimics, NR and LYS, were monitored under physiologically relevant conditions by an optimized dialysis method. The implementation of the multi-functional and semi branched polyglycidol is recognized as the main contributor for the observed highly controlled release of proteins that are otherwise rapidly released from common PEG-based nanogel networks. Furthermore, the one-pot process led to be the most favorable drug delivery system based on the release kinetics pointing to a denser polymer network. PMID- 27411980 TI - Strong linkage between plant and soil fungal communities along a successional coastal dune system. AB - Complex interactions between plants and soil microorganisms drive key ecosystem and community properties such as productivity and diversity. In nutrient-poor systems such as sand dunes, plant traits and fungal symbioses related to nutrient acquisition can strongly influence vegetation dynamics. We investigated plant and fungal communities in a relic foredune plain located on an archipelago in Quebec, Canada. We detected distinct communities across the edaphic and successional gradient. Our results showed a clear increase in plant species richness, as well as in the diversity of nutrient-acquisition strategies. We also found a strong correlation between aboveground vegetation and soil fungal communities, and both responded similarly to soil physicochemical properties. Soil pH influenced the composition of plant and fungal communities, and could act as an important environmental filter along this relic foredune plain. The increasing functional diversity in plant nutrient-acquisition strategies across the gradient might favor resource partitioning and facilitation among co-occurring plant species. The coordinated changes in soil microbial and plant communities highlight the importance of aboveground-belowground linkages and positive biotic interactions during ecological succession in nutrient-poor environments. PMID- 27411981 TI - Cyanobacterial diversity of western European biological soil crusts along a latitudinal gradient. AB - Cyanobacteria associated with biological soil crusts (BSCs) have important attributes, such as nitrogen fixation and soil stabilisation. However, research on these organisms has been minimal, and their diversity and distribution throughout temperate Europe is currently unknown. The SCIN (Soil Crust International) project is a multidisciplinary research initiative that aims to achieve improved understanding of the BSCs of Europe, one facet being an investigation into the cyanobacterial communities of BSCs across a latitudinal gradient. Cyanobacteria assemblages were analysed by both morphological and molecular analysis. Two treatments were applied prior to DNA extraction, continued sample wetting and a dry sample process, and 16S ribosomal RNA (rRNA) amplicons were processed by Illumina MiSeq sequencing. The results reveal high and variable cyanobacterial diversity with each site showing a unique assemblage. Many common cyanobacterial genera, for example Nostoc and Microcoleus, were found in all sites but the abundances of different genera varied considerably. The polyphasic approach was found to be essential in recording the presence of important cyanobacteria that a single method itself did not highlight. The wet and dry treatments showed some differences in diversity, but mainly in abundance, this may suggest how cyanobacterial composition of BSCs changes with seasonal variability. PMID- 27411982 TI - Obesity is associated with increased risk of invasive penile cancer. AB - BACKGROUND: To validate the association between obesity and penile cancer at a population level, we conducted a matched case-control study linking the Iowa Department of Motor Vehicles Drivers' License Database (DLD) with cancer surveillance data collected by the State Health Registry of Iowa (SHRI). METHODS: All men diagnosed with invasive penile squamous cell carcinoma from 1985 to 2010 were identified by SHRI. Two hundred sixty-six cancer cases and 816 cancer-free male controls, selected from the Iowa DLD, were matched within 5-year age and calendar year strata. Body mass index (BMI) was calculated using self-reported height and weight from the DLD. RESULTS: Conditional logistic regression was used to evaluate the association between BMI and the risk of developing invasive penile cancer. Obesity was significantly associated with an increased risk of developing penile cancer. For every five-unit increase in BMI the risk of invasive penile cancer increased by 53 % (OR 1.53, 95 % CI 1.29-1.81, p < 0.0001). CONCLUSION: We previously reported an association between obesity and higher risk of invasive penile cancer and advanced cancer stage at diagnosis in a hospital-based retrospective study. This population-based study confirms an association between obesity and invasive penile cancer. PMID- 27411983 TI - Predictors of non-invasive therapy and 28-day-case fatality in elderly compared to younger patients with acute myocardial infarction: an observational study from the MONICA/KORA Myocardial Infarction Registry. AB - BACKGROUND: A substantial proportion of patients with acute myocardial infarction (AMI) did not receive invasive therapy, defined as percutaneous coronary intervention and/or coronary artery bypass grafting. Aims of this study were to evaluate predictors of non-invasive therapy in elderly compared to younger AMI patients and to assess the association between invasive therapy and 28-day-case fatality. METHODS: From the German population-based registry, 3475 persons, consecutively hospitalized with an AMI between 2009 and 2012 were included. Data were collected by standardized interviews and chart review. All-cause mortality was assessed on a regular basis. Multivariable logistic regression analyses were conducted. RESULTS: The sample consisted of 1329 patients aged 28-65 years (age category [AC] 1), 1083 aged 65-74 years (AC 2), and 1063 aged 75-84 years (AC 3). The proportion of patients receiving non-invasive therapy was 10.7, 17.7, and 35.8 % in AC 1, 2, and 3, respectively. Predictors of non-invasive therapy in all ACs were non-ST segment elevation MI, bundle branch block, reduced left ventricular ejection fraction, prior stroke, absence of hyperlipidemia, and low creatine kinase. Elderly women (>=65 years) were less likely to receive invasive therapy. Stratifying the models by type of AMI revealed fewer predictors in patients with ST segment elevation MI. Regarding 28-day-case fatality, strong inverse relations with invasive therapy were seen in all AC: odds ratio of 0.35 (95 % confidence interval [CI] 0.15-0.84), 0.45 (95 % CI 0.22-0.92), and 0.39 (95 % CI 0.24-0.63) in AC 1, 2 and 3, respectively. CONCLUSION: In today's real-life patient care we found that predictors of non-invasive therapy were predominantly the same in all age groups, but differed particularly by type of AMI. Further research is necessary to investigate the real reasons for non-invasive therapy, especially among elderly women. Moreover, we confirmed that receiving invasive therapy was inversely associated with 28-day-case fatality independent of age. PMID- 27411984 TI - A population based study of drowning in Canada. AB - BACKGROUND: Although water-related fatality rates have changed over time, the epidemiology of drowning in Canada has not recently been examined. In spite of the evidence supporting varying drowning death rates by age, information on how characteristics of drowning incidents differ by age group remains limited. The primary objective of this study was to examine the epidemiology of drowning in Canada. A secondary objective was to describe the characteristics of these drowning incidents as they vary by age group. METHODS: A retrospective descriptive analysis was conducted using data that were collected for incidents occurring in Canada between January 1, 2008 and December 31, 2012. The main outcome variable was a water-related fatality, in the majority of cases (94 %) the primary cause of death was drowning. Age specific frequencies, proportions and rates per 100,000 population were calculated and compared among six age groups. RESULTS: There were 2392 unintentional water-related fatalities identified in Canada between 2008 and 2012. Death rates (per 100,000) varied by age group 0-4 (1.05), 5-14 (0.57), 15-19 (1.27), 20-34 (1.70), 35-64 (1.44), 65+ (1.74). The male to female ratio was 5:1. Differences in the characteristics of drowning by age group were identified across: sex, body of water, urban versus rural location, time of year, activity type, purpose of activity, alcohol involvement, personal flotation device use, accompaniment, and whether a rescue was attempted. CONCLUSIONS: The study results suggest that there may be a need for drowning prevention strategies that are tailored to specific age groups. Rural areas in Canada may also benefit from targeted drowning prevention. PMID- 27411986 TI - Changing patient perspectives after compulsory admission and the risk of re admission during 5 years of follow-up: The Amsterdam Study of Acute Psychiatry IX. AB - OBJECTIVE: Given increasing numbers of compulsory admissions, it is important to assess patient risk profiles and identify factors that are appropriate for intervention. METHODS: A sample of 116 patients who were compulsorily admitted was studied. Socio-demographic and clinical characteristics were recorded. Patients were interviewed twice using the Verona Service Satisfaction Scale and the Birchwood Insight Scale. Changes in insight and satisfaction during 2 years were linked to the incidence of involuntary re-admissions in the next three follow-up years. RESULTS: A higher mean score for patient satisfaction was found (mean=3.77, standard deviation (SD)=0.56; p?.001) in the second interview than in the baseline interview (mean=3.26, SD=0.65). There was also an improvement in insight (in the second interview: mean=7.22, SD=2.86 and in the baseline interview: mean=6.34, SD=3.18; p=.027). There was an inverse correlation between increasing satisfaction (in years 1-2) and the incidence of involuntary admission in years 3-5 (odds ratio (OR)=0.445, 95% confidence interval (CI)=0.252-0.793; p=.006). This association proved to be dependent on a history of involuntary admission. CONCLUSION: Increasing patient satisfaction in the first 2 years was associated with a lower risk of compulsory re-admission in the subsequent follow up period, but this association proved to be dependent on a history of involuntary admissions in these first two follow-up years. Increase in insight during the same period did not show any effect whatsoever. PMID- 27411985 TI - Combination of VP3 and CD147-knockdown enhance apoptosis and tumor growth delay index in colorectal tumor allograft. AB - BACKGROUND: Cancer therapies that kill cancer cells without affecting normal cells is the ultimate mode of treating cancers. The VP3, an avian virus-derived protein, can specifically initiate cell death through several signal transduction pathways leading to apoptosis. In cancer, chemoresistance and cell survivability implicate the cell surface protein, CD147. METHODS: In this study, transfection of VP3 and silencing of CD147 genes was achieved through the treatment of tumors with pVIVO1-GFP/VP3 (VP3), psiRNA-CD147/2 (shCD147/2), and their combination of CT26 colon cancer cell-induced in mice. The effectiveness of tumor-treatment was ascertained by electrophoresis, TUNEL assay, and flow cytometry analysis. While histopathological and biochemical analysis were used as toxic side effect identification. RESULTS: The tumor growth delay index (TGDI) after treatment with VP3, shCD147/2, and their combination treatments increased by 1.3-, 1.2-, 2.0- and 2.3-fold respectively, over untreated control. The VP3-shCD147/2 combination treatment was more efficacious then either VP3 or shCD147/2 alone in the retardation of mouse CT26 colorectal cell tumor allograft. CONCLUSION: The antitumor effect of the combination treatment is the result of synergistic effects of VP3 and shCD147/2 on the tumor cells resulting in apoptosis. Thus, the study shows that combination of VP3 and shCD147/2 treatment can be developed into a potential approach for anticolorectal cancer treatment regimen. PMID- 27411987 TI - Psychiatry's future. PMID- 27411988 TI - Developmental psychiatry needed in training and clinical practice. PMID- 27411989 TI - Disease versus illness: What do clinicians need to know? PMID- 27411990 TI - [GeSRU-StepS! - urologic surgery teaching videos at the annual meeting of the German Society for Urology]. PMID- 27411991 TI - [Anticorruption law in health care]. PMID- 27411992 TI - [Physicians make mistakes - and that is good : Cultural change for better patient safety]. PMID- 27411993 TI - [Medical-economic footprint of specialists]. PMID- 27411994 TI - [Back to the roots : Three theories about how quarrels in the KBV and in the KV system can be resolved]. PMID- 27411995 TI - [Metastatic castration-resistant prostate cancer : Clinical data, new treatment options and therapy monitoring]. AB - Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life. PMID- 27411996 TI - [Decreasing incidence of prostate cancer - hypotheses]. PMID- 27411997 TI - [Urogynaecological training situation in Germany : Gap between demand and reality]. AB - BACKGROUND: With increasing life expectancy, progressive demographic change and decreasing societal stigmatization of incontinence urologists and gynaecologists are increasingly faced with urogynaecological challenges. To date however, urogynaecology is a poorly standardized area of expertise in both disciplines. Therefore, the urogynaecology training, especially in Germany, is very heterogeneous and requires evaluation as well as improvement. MATERIALS AND METHODS: The GeSRU-Academics research group "Functional urology and LUTS" evaluated this subject nationwide among urological and gynecological trainees and their chief physicians by using a comprehensive questionnaire (34/38 multiple choice items) between April 2015 and May 2016. RESULTS: 336 urological residents and 190 chief physicians as well as 171 gynaecological residents and 175 chief physicians participated in the survey. Of all trainees, 70.0 % stated a personal interest in urogynaecology, but 45.4 % (gynaecological residents) and 52.9 % (urological residents) mention not to receive a standardized training in their own department. The chief physicians' survey resulted in discrepancies concerning the same question, <10 % of all residents do not receive a standardized urogynaecological training from their point of view. However, standardized urogynaecological training is of importance for those chief physicians. CONCLUSIONS: There is a discrepancy between expectations and reality of urogynaecological education and training. To enable a well-structured and standardized urogynaecological education and training, it is compulsory to focus on an interdisciplinary cooperation and to promote multidisciplinary development. A broad-based, well-designed training network and curricula should be established and used consistently. PMID- 27411998 TI - [Generation Y : Problem or solution in daily clinical practice]. PMID- 27411999 TI - [Primitive neuroendocrine/ectodermal kidney tumor]. AB - PNET of the kidney are rare, aggressive tumors that occur mainly in adolescents. The diagnosis of PNET is difficult, but is possible with pathognomonic radiological findings. Since a radical nephrectomy is generally not sufficient for PNET of the kidney, early diagnosis and treatment is essential for successful recovery. PMID- 27412000 TI - The incidence and significance of multicentric noncontrast-enhancing lesions distant from a histologically-proven glioblastoma. AB - Improvements in imaging are increasing the detection of multiple lesions in the setting of glioblastoma. Occasionally distant non-enhancing lesions may be identified which have the appearances of a multicentric low-grade glioma. We aimed to determine the incidence, prognostic significance and diagnostic value of this appearance in new glioblastoma patients. Pre-operative MRIs of patients with a new diagnosis of glioblastoma were reviewed to identify multicentric non enhancing lesions, defined as areas of FLAIR hyperintensity and mass effect, without post-contrast enhancement, separate from the histologically-proven glioblastoma. Patient survival was compared to glioblastoma patients without these appearances, and follow-up imaging was reviewed. Nine of 151 patients (6 %) had multicentric non-enhancing lesions. Their median survival of 183 days was significantly worse than the 278 days for patients without multicentric nonenhancing lesions (p = 0.025). Follow-up MRIs were performed in four patients. In one patient, there were several additional lesions, one of which developed evidence of necrosis within 22 days of presentation. In the other three patients, the multicentric lesions developed enhancement and evidence of necrosis within 1 year, and became confluent on FLAIR with the dominant lesion. The appearance of a multicentric non-enhancing lesion is an uncommon finding in glioblastoma, but a poor prognostic feature. These lesions progress faster than expected for a low grade glioma and are thus likely to represent more advanced lesions than their appearances suggest. Confluence with the dominant lesion developing with time suggests that the tumor is more extensive than appreciated on imaging. PMID- 27412001 TI - Deciphering the real incidence of medulloblastoma with extensive nodularity in adult patients. PMID- 27412002 TI - Dyadobacter endophyticus sp. nov., an endophytic bacterium isolated from maize root. AB - A novel Gram-stain-negative, aerobic and rod-shaped bacterial strain, designated 65T, was isolated from surface-sterilized root tissue of maize, collected from Fangshan District of Beijing, People's Republic of China, and was subjected to a taxonomic study by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 65T belonged to the genus Dyadobacter and had highest 16S rRNA gene sequence similarity to Dyadobacter jiangsuensis CGMCC 1.12969T (99.1 %), Dyadobacter beijingensis CGMCC 1.6375T (98.8 %), Dyadobacter fermentans DSM 18053T (98.6 %) and Dyadobacter soli KCTC 22481T (98.6 %). However, the new isolate exhibited relatively low levels of DNA-DNA relatedness with respect to D. jiangsuensis CGMCC 1.12969T (18.2+/-1.3 %), D. beijingensis CGMCC 1.6375T (14.2+/-2.0 %), D. fermentans DSM 18053T (14.1+/-2.0 %) and D. soli KCTC 22481T (13.8+/-0.6 %). The predominant respiratory quinone was menaquinone-7 (MK-7) and the major cellular fatty acids were summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH), iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1omega5c, iso-C15 : 0 3-OH, C16 : 0 3-OH and C16 : 0. The polar lipid profile of strain 65T revealed the presence of phosphatidylethanolamine, four aminolipids and two unidentified phospholipids. The DNA G+C content was 46.6 mol%. The results of physiological and biochemical tests and the differences in the fatty acid profiles allowed the clear phenotypic differentiation of strain 65T from closely related species of the genus Dyadobacter. Strain 65T thus represents a novel species within the genus Dyadobacter, for which the name Dyadobacterendophyticus sp. nov. is proposed. The type strain is 65T (=CGMCC 1.15288T=DSM 100786T). PMID- 27412003 TI - Learning about natural variation of odor mixtures enhances categorization in early olfactory processing. AB - Natural odors are typically mixtures of several chemical components. Mixtures vary in composition among odor objects that have the same meaning. Therefore a central 'categorization' problem for an animal as it makes decisions about odors in natural contexts is to correctly identify odor variants that have the same meaning and avoid variants that have a different meaning. We propose that identified mechanisms of associative and non-associative plasticity in early sensory processing in the insect antennal lobe and mammalian olfactory bulb are central to solving this problem. Accordingly, this plasticity should work to improve categorization of odors that have the opposite meanings in relation to important events. Using synthetic mixtures designed to mimic natural odor variation among flowers, we studied how honey bees learn about and generalize among floral odors associated with food. We behaviorally conditioned honey bees on a difficult odor discrimination problem using synthetic mixtures that mimic natural variation among snapdragon flowers. We then used calcium imaging to measure responses of projection neurons of the antennal lobe, which is the first synaptic relay of olfactory sensory information in the brain, to study how ensembles of projection neurons change as a result of behavioral conditioning. We show how these ensembles become 'tuned' through plasticity to improve categorization of odors that have the different meanings. We argue that this tuning allows more efficient use of the immense coding space of the antennal lobe and olfactory bulb to solve the categorization problem. Our data point to the need for a better understanding of the 'statistics' of the odor space. PMID- 27412004 TI - A Review of Dysphagia Presentation and Intervention Following Traumatic Spinal Injury: An Understudied Population. AB - Dysphagia is reported to be a common secondary complication for individuals with traumatic spinal injuries. Different etiologies of traumatic spinal injuries may lead to different profiles of swallowing impairment. We conducted a systematic review to determine the characteristics of dysphagia after traumatic spinal injury and to describe interventions currently used to improve swallowing function in this population. A comprehensive multiengine literature search identified 137 articles of which five were judged to be relevant. These underwent review for study quality, rating for level of evidence, and data extraction. The literature describing dysphagia after traumatic spinal injury was comprised predominantly of low-level evidence and single case reports. Aspiration, pharyngeal residue, and decreased/absent hyolaryngeal elevation were found to be common characteristics of dysphagia in this population. The most commonly used swallowing interventions included tube feeding, compensatory swallowing strategies, and steroids/antibiotics. Improvement in swallowing function following swallowing intervention was reported in all studies; however, there was no control for spontaneous recovery. The results demonstrate a need for high quality research to profile the pathophysiology of dysphagia after traumatic spinal injury and controlled studies to demonstrate the efficacy of swallowing interventions in this population. PMID- 27412005 TI - Understanding the Viscosity of Liquids used in Infant Dysphagia Management. AB - When assessing swallowing in infants, it is critical to have confidence that the liquids presented during the swallow study closely replicate the viscosity of liquids in the infant's typical diet. However, we lack research on rheological properties of frequently used infant formulas or breastmilk, and various forms of barium contrast media used in swallow studies. The aim of the current study was to provide objective viscosity measurements for typical infant liquid diet options and barium contrast media. A TA-Instruments AR2000 Advanced Rheometer was used to measure the viscosity of five standard infant formulas, three barium products, and two breastmilk samples. Additionally, this study measured the viscosity of infant formulas and breastmilk when mixed with powdered barium contrast in a 20 % weight-to-volume (w/v) concentration. The study findings determined that standard infant formulas and the two breastmilk samples had low viscosities, at the lower end of the National Dysphagia Diet (NDD) thin liquid range. Two specialty formulas tested had much thicker viscosities, close to the lower boundary of the NDD nectar-thick liquid range. The study showed differences in viscosity between 60 % w/v barium products (Liquid E-Z-Paque((r)) and E-Z Paque((r)) powder); the powdered product had a much lower viscosity, despite identical barium concentration. When E-Z-Paque((r)) powdered barium was mixed in a 20 % w/v concentration using water, standard infant formulas, or breastmilk, the resulting viscosities were at the lower end of the NDD thin range and only slightly thicker than the non-barium comparator liquids. When E-Z-Paque((r)) powdered barium was mixed in a 20 % w/v concentration with the two thicker specialty formulas (Enfamil AR 20 and 24 kcal), unexpected alterations in their original viscosity occurred. These findings highlight the clinical importance of objective measures of viscosity as well as objective data on how infant formulas or breastmilk may change in consistency when mixed with barium. PMID- 27412007 TI - Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic. AB - Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC. PMID- 27412006 TI - Benefit-Risk Assessment of Fish Oil in Preventing Cardiovascular Disease. AB - Cardiovascular disease (CVD) is a preventable disease, which combines two general processes: chronic vascular inflammation and acute thrombosis. Both are amplified with positive feedback signals by n-6 eicosanoids derived from food-based n-6 highly unsaturated fatty acids (n-6 HUFA). This amplification is lessened by competing actions of n-3 HUFA. Death results from fatal interactions of the vascular wall with platelets and clotting proteins. The benefits of fish oil interventions are confounded by complex details in pharmacokinetics, pharmacodynamics, adverse events, timescale factors, topology, financial incentives and people's sense of cause and effect. Two basic aspects of n-3 HUFA that are overlooked in CVD dynamics are saturable, hyperbolic responses of the enzymes continually supplying n-6 HUFA and hard-to-control positive feedback receptor signals by excessive n-6 HUFA-based mediators. Multiple feedback loops in inflammation and thrombosis have diverse mediators, and reducing one mediator that occurs above its rate-limiting levels may not reduce the pathophysiology. Clinicians have developed some successful interventions that decrease CVD deaths in the form of secondary prevention. However, the current high CVD prevalence in the USA remains unchanged, and successful primary prevention of CVD remains uncertain. This review weighs the available evidence to help clinicians, the biomedical community and the public put the use of fish oil supplements into a balanced perspective. PMID- 27412009 TI - Pathogenetics of the RASopathies. AB - The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. The consequence of germ-line dysregulation leads to phenotypic alterations of development. RASopathies can be caused by several pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. These pathogenetic mechanisms can include functional alteration of GTPases, Ras GTPase-activating proteins, Ras guanine exchange factors, kinases, scaffolding or adaptor proteins, ubiquitin ligases, phosphatases and pathway inhibitors. Although these mechanisms are diverse, the common underlying biochemical phenotype shared by all the RASopathies is Ras/MAPK pathway activation. This results in the overlapping phenotypic features among these syndromes. PMID- 27412008 TI - Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta. AB - Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI. However, no AMTN mutations have yet been associated with human AI. Using whole exome sequencing, we identified an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues. Exfoliated primary teeth from an affected family member had enamel that was of a lower mineral density compared to control enamel and exhibited structural defects at least some of which appeared to be associated with organic material as evidenced using elemental analysis. This study demonstrates for the first time that AMTN mutations cause non-syndromic human AI and explores the human phenotype, comparing it with that of mice with disrupted Amtn function. PMID- 27412010 TI - Molecular disturbance underlies to arrhythmogenic cardiomyopathy induced by transgene content, age and exercise in a truncated PKP2 mouse model. AB - Arrhythmogenic cardiomyopathy (ACM) is a disorder characterized by a progressive ventricular myocardial replacement by fat and fibrosis, which lead to ventricular arrhythmias and sudden cardiac death. Mutations in the desmosomal gene Plakophilin-2 (PKP2) accounts for >40% of all known mutations, generally causing a truncated protein. In a PKP2-truncated mouse model, we hypothesize that content of transgene, endurance training and aging will be determinant in disease progression. In addition, we investigated the molecular defects associated with the phenotype in this model. We developed a transgenic mouse model containing a truncated PKP2 (PKP2-Ser329) and generated three transgenic lines expressing increasing transgene content. The pathophysiological features of ACM in this model were assessed. While we did not observe fibro-fatty replacement, ultrastructural defects were exhibited. Moreover, we observed transgene content dependent development of structural (ventricle dilatation and dysfunction) and electrophysiological anomalies in mice (PR interval and QRS prolongation and arrhythmia induction). In concordance with pathological defects, we detected a content reduction and remodeling of the structural proteins Desmocollin-2, Plakoglobin, native Plakophilin-2, Desmin and beta-Catenin as well as the electrical coupling proteins Connexin 43 and cardiac sodium channel (Nav1.5). Surprisingly, we observed structural but not electrophysiological abnormalities only in trained and old mice. We demonstrated that truncated PKP2 provokes ACM in the absence of fibro-fatty replacement in the mouse. Transgene dose is essential to reveal the pathology, whereas aging and endurance training trigger limited phenotype. Molecular abnormalities underlay the structural and electrophysiological defects. PMID- 27412011 TI - Genetics and immunity in the era of single-cell genomics. AB - Recent developments in the field of single-cell genomics (SCG) are changing our understanding of how functional phenotypes of cell populations emerge from the behaviour of individual cells. Some of the applications of SCG include the discovery of new gene networks and novel cell subpopulations, fine mapping of transcription kinetics, and the relationships between cell clonality and their functional phenotypes. Immunology is one of the fields that is benefiting the most from such advancements, providing us with completely new insights into mammalian immunity. In this review, we start by covering new immunological insights originating from the use of single-cell genomic tools, specifically single-cell RNA-sequencing. Furthermore, we discuss how new genetic study designs are starting to explain inter-individual variation in the immune response. We conclude with a perspective on new multi-omics technologies capable of integrating several readouts from the same single cell and how such techniques might push our biological understanding of mammalian immunity to a new level. PMID- 27412013 TI - Over-expression of DNA-PKcs in renal cell carcinoma regulates mTORC2 activation, HIF-2alpha expression and cell proliferation. AB - Here, we demonstrated that DNA-PKcs is over-expressed in multiple human renal cell carcinoma (RCC) tissues and in primary/established human RCCs. Pharmacological or genetic inhibition of DNA-PKcs suppressed proliferation of RCC cells. DNA-PKcs was in the complex of mTOR and SIN1, mediating mTORC2 activation and HIF-2alpha expression in RCC cells. Inhibiting or silencing DNA-PKcs suppressed AKT Ser-473 phosphorylation and HIF-2alpha expression. In vivo, DNA PKcs knockdown or oral administration of the DNA-PKcs inhibitor NU-7441 inhibited AKT Ser-473 phosphorylation, HIF-2alpha expression and 786-0 RCC xenograft growth in nude mice. We showed that miRNA-101 level was decreased in RCC tissues/cells, which could be responsible for DNA-PKcs overexpression and DNA-PKcs mediated oncogenic actions in RCC cells. We show that DNA-PKcs over-expression regulates mTORC2-AKT activation, HIF-2alpha expression and RCC cell proliferation. PMID- 27412012 TI - A genome-wide association meta-analysis on apolipoprotein A-IV concentrations. AB - Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 * 10 - 44), rs5104 in APOA4 (P = 1.79 * 10-24) and rs4241819 in KLKB1 (P = 5.6 * 10-14). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 * 10 - 07). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 * 10-05). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations. PMID- 27412015 TI - [Quantitative gait analysis in patients with advanced Parkinson's disease]. AB - AIM: To describe the gait disorders and postural instability in a group of patients with advanced Parkinson's disease (PD). PATIENTS AND METHODS: Gait was analysed in patients in advanced stages of PD on medication. Using a computerised analysis system, we studied the kinematic variables: cadence, number of correct gait cycles (HFPS cycles), total number of cycles, duration of the phases of the cycle, electromyography and a goniometric study of the knee and the ankle. The clinical appraisal of balance and postural instability was completed with the Tinetti and Timed Up and Go tests. RESULTS: The analysis showed alterations in the spatio-temporal parameters with respect to the ranges considered to be normal: reduction of the HFPS cycles, increase in the total number of cycles and alteration of the cadence in many patients. It also revealed that the mean cadence was kept within the limits of normal values, an increase in the duration of the contact phase, reduction of monopodal support and alteration of the joint range of motion of the knee and the ankle. Likewise, changes are also observed in the scores obtained on the clinical scales, which show an increase in the risk factor for falls and mild dependence. CONCLUSION: Quantification by objective analysis of the kinetic and kinematic variables in patients with PD can be used as a tool to establish the influence of the different therapeutic alternatives in gait disorders. PMID- 27412016 TI - [Optic neuritis in childhood. A pediatric series, literature review and treatment approach]. AB - INTRODUCTION: In children, the most common form of optic neuritis usually occurs after an infectious disease with papilledema, usually bilateral and has a good prognosis. Conversion to multiple sclerosis is low. AIM: To present clinical and laboratory case of optic neuritis in pediatrics features. PATIENTS AND METHODS: Seventeen clinical cases of optic neuritis in children and young people aged 4-14 years, referred from 2000 to 2015 were analyzed. RESULTS: The median age of the series was 11 years. They predominated the female patients and infectious history was uncommon; in five of 17 patients was bilateral engagement and four cases evolved with retrobulbar optic neuritis. Magnetic resonance imaging showed hyperintensity on T2 in the optic nerves affected in five patients. The study of cerebrospinal fluid and oligoclonal bands was normal in all cases. Patients treated with intravenous methylprednisolone had good recovery. It was found subsequent evolution to multiple sclerosis only in three cases. CONCLUSIONS: In our series, the cases that evolved multiple sclerosis showed no clinical differences although they had a higher number of hyperintense lesions on magnetic resonance imaging. This fact, described in previous studies, supports our diagnostic and therapeutic scheme in an attempt to approach the optimal management of this disease. PMID- 27412014 TI - Single-cell genome-wide studies give new insight into nongenetic cell-to-cell variability in animals. AB - Huge numbers of cells form an adult animal body, ranging from several thousands in Placozoa and small nematodes to many billions in mammals. Cells are classified into separate groups known as cell types by their morphological and biochemical features. Six to several hundreds of spatially ordered cell types are recognized in different animals. This complex organization develops from one cell, a zygote, during ontogeny, and its dynamic equilibrium is often maintained in the adult body. One of the key challenges in biology is to understand the mechanisms that sustain the reproducible development of a complex ordered cell ensemble such as the animal body from a single cell. How cells with identical genomes stably maintain one of the numerous possible phenotypes? How the cell differentiation lineage is selected during development? What genes play a key role in maintaining cell identity, and how do they determine expression of other genes characteristic of the relevant cell type? How does the basically stochastic nature of transcription in an isolated cell affect the stability of cell identity, the selection of a cell lineage, and the variability of cell responses to external stimuli? Better-grounded answers to these questions have become possible with recent progress in single-cell genome-wide analysis techniques, which combine the high throughput of biochemical methods and the differential nature of microscopy. The techniques are still in their infancy, and their further development will certainly revolutionize many fields of life sciences and, in particular, developmental biology. Here, we summarize the main results that have been obtained in single-cell genome-wide analyses and describe the nongenetic cell-to cell variability in animals. PMID- 27412017 TI - [Effectiveness of functional electrical stimulation in stroke patients: a systematic review]. AB - INTRODUCTION: Functional electrical stimulation is one of the physiotherapy techniques used today for the management of patients who have suffered a stroke. AIM: To determine the effectiveness of the functional electrical stimulation in general skills, gait, general capacities and quality of stroke patients through a systematic review. Also has secondary objective was raised to know the best method of application of this technique. PATIENTS AND METHODS: We performed a literature search in Medline, PEDro and Cochrane Library. Clinical trials and systematic reviews about the effectiveness of the functional electrical stimulation in stroke patients from last five years were included. RESULTS: Ten clinical trials and one systematic review were included and we analyzed and compared the most relevant data extracted of them. CONCLUSIONS: Functional electrical stimulation shows an improvement in the quality of life, motor abilities and gait in stroke patients. It is more effective associated with other physiotherapy techniques. Functional electrical stimulation alone does not provide better results than other physiotherapy techniques. The implementation of the technique in more than one muscle group, triggering impulses by active movements and associating with other interventions, is the best approach to application of functional electrical stimulation. PMID- 27412018 TI - [Central nervous system in IgG4-related disease: case report and literature review]. AB - INTRODUCTION: IgG4-related disease is a recently described multisystemic clinical entity that can occur with different clinical manifestations. The most often affected organs are the pancreas, bile duct and salivary glands, with unusual central nervous system affection. CASE REPORT: A 33 year old woman who presented with cognitive impairment, hallucinations, headache, convulsive syndrome, maxillary sinus inflammation with bone involvement and evidence of pachymeningitis and panhypopytuirarism with meningeal biopsy that confirmed IgG4 related disease, after ruling out secondary causes. Treatment was started with steroids and azathioprine without relapses after 12 months follow-up. CONCLUSIONS: IgG4-related disease should be considered in cases of hypertrophic pachymeningitis and hypophysitis especially when no other cause has been found, even if they are not accompanied by other systemic disease manifestations, having ruled out other common causes. The treatment of choice is glucocorticoids and it could be needed to add another immuno-suppressant agent as steroid sparing and to prevent relapses. Prospective studies are needed to evaluate the different clinical and paraclinical manifestations and to establish the results of long term treatment. PMID- 27412019 TI - [Neuropsychological alterations are frequent in rolandic epilepsy and its atypical developments]. AB - INTRODUCTION: Rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes is called benign because its seizures are usually favourable and due to the spontaneous normalisation of the electroencephalogram on reaching puberty. Nevertheless, evidence has been found of the impact on cognitive development with the presence of heterogeneous cognitive deficits, especially related to persistent intercritical discharges during non-REM sleep. The aim of this study is to examine the epileptogenic networks involved in the neuropsychological disorders of this pathology. DEVELOPMENT: A common feature of the atypical developments is persistent epileptic activity during slow sleep, which plays an important role in the development of the neurocognitive deficits that are associated to this pathology. Factors such as the age at onset of the epilepsy, the onset of the atypical development, the location of the interictal discharges and the continuous epileptic activity during sleep that persists for more than two years can trigger changes in the functioning of the neurocognitive networks. This may result in deficits in the neuropsychological functions, which may even be irreversible. CONCLUSIONS: A close clinical and electroencephalographic follow up is necessary. Moreover, formal neuropsychological studies must be conducted as of the onset of benign childhood epilepsy with centrotemporal spikes. This is even more necessary in cases in which there is an obvious atypical development in order to detect and prevent the neuropsychological deficits before they establish themselves on a definitive basis. PMID- 27412020 TI - [The mind-brain problem (I): onto-epistemological foundations]. AB - INTRODUCTION: Throughout the history of thought, science and philosophy have addressed the problem of mind-brain from different epistemic perspectives. The first covers specific areas of reality and constructs hypotheses with limited scope and multiple inter-scientific connectivity with the aim of validating theoretical models; the second extends its systemic architecture to all that is real (including scientific activity). DEVELOPMENT: The complexity of the mind brain problem requires the generation of a link connecting the disciplines of philosophy and science; our onto-epistemological presuppositions therefore fall within the framework of a scientifically-oriented philosophy (scientific philosophy). Emergentist materialism is defended as a coherent and verifiable philosophical-scientific solution, as opposed to other proposals developed on the basis of different ontological models (for example, interactionist dualism, functionalism, theory of identity, epiphenomenalism, and so on). CONCLUSIONS: An answer to the mind-brain problem is only feasible if based on a philosophically grounded cognitive neuroscience: emergentist materialism -an ontological postulate- holds that the mind is an emergent property (qualitative novelty) of the brain; scientific realism -an epistemological postulate- holds that cognitive neuroscience is the basic theoretical-experimental tool that allows cognitive access to both the brain and its neurocognitive processes. We consider that on the basis of this philosophical reasoning, cognitive neuroscience acquires epistemic legitimacy to be able to undertake the study of the most genuinely human mental process: consciousness. PMID- 27412021 TI - [Eslicarbazepine in patients with hipercholesterolemia associated to carbamazepine and oxcarbacepine]. PMID- 27412022 TI - [Cryoglobulinemia type II with double neuropathy not associated with hepatitis C infection]. PMID- 27412023 TI - [Epidemiology and neurological complications of infection by the Zika virus: a new emerging neurotropic virus]. PMID- 27412024 TI - [Epidemiology and neurological complications of infection by the Zika virus: a new emerging neurotropic virus. Reply]. PMID- 27412025 TI - Evaluation of esophageal intramural pseudo-diverticulosis using high-resolution manometry. AB - Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disease characterized by multiple small flask-shaped pouches in the esophageal wall, with the predominant symptom of chronic progressive or intermittent dysphagia. However, its etiology and pathogenesis remain unknown. We present a case of EIPD evaluated with high-resolution manometry in a 75-year-old man with food impaction after eating beef, who came to our emergency department. The patient experienced similar episodes three times previously, though the cause was unknown. Computed tomography (CT) findings revealed diffuse wall thickness in the upper intrathoracic esophagus, while esophagogastroduodenoscopy showed multiple small depressions and several white plaque patches, and a barium meal esophagogram showed characteristic multiple small outpouching areas. From these findings, we diagnosed the patient with EIPD. In addition, high-resolution manometry revealed strong contractions in the distal esophagus. We started an administration of isosorbide dinitrate, because abnormal esophageal motility may have been causative of the condition and development of pseudo-diverticulosis. Thereafter, the patient had a good clinical course without food impaction. Elevated intra esophageal luminal pressure caused by abnormal esophageal motility seems to be an important factor in the pathogenesis of EIPD in some cases. PMID- 27412026 TI - Multiple colonic ulcers associated with trisomy 8: serial changes in colonoscopic findings. AB - We report a 54-year-old female patient with myelodysplastic syndrome (MDS) associated with trisomy 8, who had multiple colonic ulcers. The patient had been diagnosed as having MDS of refractory cytopenia with trisomy 8 10 years previously. She underwent colonoscopy for abdominal pain, which revealed severe circumferential stenosis with multiple ulcers in the ileocecal region and a discrete excavating ulcer in the transverse colon. The patient had been free from any dermatological, oral, genital or ocular symptoms suggestive of Behcet's disease (BD). A diagnosis of multiple colonic ulcers associated with MDS with trisomy 8 was thus suggested. Follow-up colonoscopies 5 and 6 years later revealed progression of the ileocecal stenosis to a circumferential ulcer, while the ulcer in the transverse colon had not changed. Because our patient lacked extraintestinal symptoms of BD, trisomy 8 was presumed to be responsible for her colonic ulcers. PMID- 27412027 TI - Subsurface Space-Charge Dopant Segregation to Compensate Surface Excess Charge in a Perovskite Oxide. AB - Since the first prediction by Frenkel, many follow-up studies have been carried out to show the presence of subsurface space-charge layers having the opposite sign to that of the excess charge at the surface, producing overall neutrality in ionic crystals. However, no precise experimental evidence demonstrating how the aliovalent solutes segregate in the space-charge region beneath the surface has been provided over the past several decades. By utilizing atomic-scale imaging and chemical probing in a perovskite oxide, the origin of the surface excess charge at the topmost surface and the position of segregated dopants in the space charge region is precisely determined. The impact of the space-charge contribution to the dopant distribution near the surface in oxide crystals is explored. PMID- 27412028 TI - Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment. AB - Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was >=5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH4Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH4Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA. PMID- 27412029 TI - N3DFix: an Algorithm for Automatic Removal of Swelling Artifacts in Neuronal Reconstructions. AB - It is well established that not only electrophysiology but also morphology plays an important role in shaping the functional properties of neurons. In order to properly quantify morphological features it is first necessary to translate observational histological data into 3-dimensional geometric reconstructions of the neuronal structures. This reconstruction process, independently of being manual or (semi-)automatic, requires several preparation steps (e.g. histological processing) before data acquisition using specialized software. Unfortunately these processing steps likely produce artifacts which are then carried to the reconstruction, such as tissue shrinkage and formation of swellings. If not accounted for and corrected, these artifacts can change significantly the results from morphometric analysis and computer simulations. Here we present N3DFix, an open-source software which uses a correction algorithm to automatically find and fix swelling artifacts in neuronal reconstructions. N3DFix works as a post processing tool and therefore can be used in either manual or (semi-)automatic reconstructions. The algorithm's internal parameters have been defined using a "ground truth" dataset produced by a neuroanatomist, involving two complementary manual reconstruction procedures: in the first, neuronal topology was faithfully reconstructed, including all swelling artifacts; in the second procedure a meticulous correction of the artifacts was manually performed directly during neuronal tracing. The internal parameters of N3DFix were set to minimize the differences between manual amendments and the algorithm's corrections. It is shown that the performance of N3DFix is comparable to careful manual correction of the swelling artifacts. To promote easy access and wide adoption, N3DFix is available in NEURON, Vaa3D and Py3DN. PMID- 27412032 TI - Erratum to: The efficacy of lymphatic drainage and traditional massage in the prophylaxis of migraine: a randomized, controlled parallel group study. PMID- 27412031 TI - Aflibercept, a New Way to Target Angiogenesis in the Second Line Treatment of Metastatic Colorectal Cancer (mCRC). AB - Colorectal cancer (CRC) is a leading tumour worldwide, and the median survival of metastatic patients with the latest therapeutic options today reaches 30 months. Therefore, it is important to plan a therapeutic strategy, able to optimize the use of the available drugs (fluoropyrimides, oxaliplatin, irinotecan and target biologic therapy), with the objective of maximizing the long-term efficacy, reducing toxicities and assuring better quality of life for the patients with mCRC. Among the most recently available drugs for the treatment of mCRC, aflibercept, a new antiangiogenetic agent, should be considered a promising therapeutical option for the second line setting. In this review, the mechanism of action and preclinical evidence, as well as pharmacological and clinical aspects of aflibercept will be analysed. In particular, this drug has a peculiar and unique mechanism of action, inhibiting VEGF-A, -B and PlGF pathways, which may help to overcome tumour escape mechanisms to bevacizumab treatment. From a clinical point of view, the addition of aflibercept to FOLFIRI regimen was able to significantly improve all the clinical outcome with respect to the chemotherapy alone in second line treatment of mCRC patients, regardless of age, RAS status, and prior use of bevacizumab. Finally, the safety profile of aflibercept is well known and manageable in most of the patients. Aflibercept can be considered a novel standard of care in the second line setting and an important therapeutic option for mCRC patients. PMID- 27412030 TI - Age-period-cohort analysis of suicide mortality by gender among white and black Americans, 1983-2012. AB - BACKGROUND: Previous studies suggested that the racial differences in U.S. suicide rates are decreasing, particularly for African Americans, but the cause behind the temporal variations has yet to be determined. This study aims to investigate the long-term trends in suicide mortality in the U.S. between 1983 and 2012 and to examine age-, period-, and cohort-specific effects by gender and race. METHOD: Suicide mortality data were collected from the Web-based Injury Statistics Query and Reporting System (WISQARS) and analyzed with the Joinpoint regression and age-period-cohort (APC) analysis. RESULTS: We found that although age-standardized rate of suicide in white males, white females, black males, and black females all changed at different degrees, the overall situation almost has not changed since these changes offset each other. By APC analysis, while the age effect on suicide demonstrate an obvious difference between white males and females (with the peak at 75 to 79 for white males and 45 to 54 for white females), young black people are predominantly susceptible to suicide (risk peaks in early 20s for black males and late 20s for black females). Cohort effects all showed a descending trend, except that in white males and females which showed an obvious increase peaked in around cohort 1960. There was a similar period effect trend between different genders in the same race group, but between the races, differences were found in the period before 1990 and after 2000. CONCLUSION: We confirmed that the distinction in age-specific suicide rate patterns does exist by gender and by race after controlling for period and cohort effects, which suggested that minorities' age patterns of suicide may have been masked up by the white people in the whole population. The differences of period effects and cohort effects between white and black Americans were likely to be mainly explained by the difference in race susceptibility to economic depression. PMID- 27412033 TI - Is lipoprotein (a) protective of dementia? AB - Lipoprotein(a) [Lp(a)]-an established risk factor for vascular disease, has been suggested to be associated with risk of dementia, however no prospective evidence exists to support this finding. We aimed to assess the association of Lp(a) with dementia risk. Lp(a) concentration was assessed at baseline in a prospective cohort of 2532 men aged 42-61 years. During a median follow-up of 24.9 years, 228 new cases of dementia were recorded. Lp(a) was approximately log-linearly associated with dementia risk. In age-adjusted analysis, the hazard ratio for dementia in a comparison of extreme quartiles of Lp(a) levels was 0.68 (95 % CI: 0.47-0.99), which persisted after adjustment for several physical measures, history of coronary heart disease, smoking status, history of diabetes, serum lipids, alcohol consumption, and socio-economic status 0.68 (0.46-0.99). Lp(a) is protective of future dementia risk in a middle-aged male Caucasian population. Further research is needed replicate these findings. PMID- 27412034 TI - Femtosecond insights into direct electron injection in dye anchored ZnO QDs following charge transfer excitation. AB - The role of the charge transfer (CT) state in interfacial electron transfer in dye-sensitized semiconductor nanocrystals is still poorly understood. To address this problem, femtosecond transient absorption (TA) spectroscopy is used as a probe to investigate the electron injection across a newly synthesized coumarin dye (8-hydroxy-2-oxo-4-phenyl-2 benzo[h]chromene-3-carbonitrile, coded BC5) and ZnO quantum dots (QDs). Steady state and time-resolved spectroscopic measurements reveal that BC5 dye interacts strongly with ZnO QDs in the ground state forming a CT complex. The BC5-ZnO QD complex absorbs more towards red compared to only the dye and QDs, and emits fluorescence due to radiative recombination of photogenerated charges. The formation of charges following the excitation of the CT complex has been demonstrated by observing the signature of dye radical cations and electrons in the conduction band (CB) of the QDs in the TA spectra. The TA signals of these charges grow sharply as a result of ultrafast direct electron injection into the QD. We have monitored the complete dynamics of photogenerated charges by measuring the TA signals of the charges up to a couple of nanoseconds. The injected electrons that are free or shallowly trapped recombine with a time constant of 625 fs, whereas deeply trapped electrons disappear slowly (526 ps) via radiative recombination. Furthermore, theoretical studies based on ab initio calculations have been carried out to complement the experimental findings. PMID- 27412036 TI - Echocardiography training for cardiac surgery residents: results of a Canadian needs assessment. AB - BACKGROUND: In assessing an unstable patient post cardiac surgery, echocardiography can be an essential tool as part of this assessment. However, it may be under-utilized for several reasons. We conducted this study to determine the perceived needs and training objectives for echocardiography training for cardiac surgery residents. METHODS: This study was a cross-sectional, stratified national survey of cardiac surgery residents, cardiac surgeons, cardiac surgery program directors and cardiologists, designed to acquire opinions on what type and level of objective-based training in echocardiography is required for cardiac surgery residents. Recruitment of survey subjects was through Fluid Surveys email invitations to 201 physicians. Participants were asked to rate the importance of focused echocardiography training for cardiac surgery residents and also give a grade of importance for 18 training objectives. RESULTS: We received 89 completed surveys. More than 80 % of responders feel that echocardiography training should be required for cardiac surgery residents. Forty seven percent of all responders felt that residents should take an echocardiography course with or without a rotation to train in echocardiography. Thirty five percent felt that current training in most programs, which entails a single rotation in echocardiography, is sufficient. Seven training objectives were identified as important by more than 80 % of participants. CONCLUSION: Study participants believe that cardiac surgery residents require echocardiography training. The majority agree that echocardiography training should be informed by the identified 7 training objectives. PMID- 27412035 TI - Productive replication of nephropathogenic infectious bronchitis virus in peripheral blood monocytic cells, a strategy for viral dissemination and kidney infection in chickens. AB - In the present study, the replication kinetics of nephropathogenic (B1648) and respiratory (Massachusetts-M41) IBV strains were compared in vitro in respiratory mucosa explants and blood monocytes (KUL01(+) cells), and in vivo in chickens to understand why some IBV strains have a kidney tropism. B1648 was replicating somewhat better than M41 in the epithelium of the respiratory mucosa explants and used more KUL01(+) cells to penetrate the deeper layers of the respiratory tract. B1648 was productively replicating in KUL01(+) monocytic cells in contrast with M41. In B1648 inoculated animals, 10(2.7-6.8) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8, 10 and 12 days post inoculation (dpi), 10(2.4-4.5) viral RNA copies/mL in plasma at 2, 4, 6, 8, 10 and 12 dpi and 10(1.8-4.4) viral RNA copies/10(6) mononuclear cells in blood at 2, 4, 6 and 8 dpi. In M41 inoculated animals, 10(2.6-7.0) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8 and 10 dpi, but viral RNA was not demonstrated in plasma and mononuclear cells (except in one chicken at 6 dpi). Infectious virus was detected only in plasma and mononuclear cells of the B1648 group. At euthanasia (12 dpi), viral RNA and antigen positive cells were detected in lungs, liver, spleen and kidneys of only the B1648 group and in tracheas of both the B1648 and M41 group. In conclusion, only B1648 can easily disseminate to internal organs via a cell-free and -associated viremia with KUL01(+) cells as important carrier cells. PMID- 27412037 TI - The effect of badminton-specific exercise on badminton short-serve performance in competition and practice climates. AB - This study examined the effects of changes in physiological and psychological arousal on badminton short-serve performance in competitive and practice climates. Twenty competitive badminton players (10 males and 10 females) volunteered to participate in the study following ethics approval. After familiarisation, badminton short-serve performance was measured at rest, mid-way through and at the end of a badminton-specific exercise protocol in two conditions; competition vs. practice. Ratings of cognitive and somatic anxiety were assessed at three time points prior to badminton short-serve performance using the Mental Readiness Form 3. Heart rate and rating of perceived exertion (RPE) were assessed during the exercise protocol. Results indicated that better short-serve performance was evident in practice compared to competition (P = .034). RPE values were significantly higher in the competition condition compared to practice (P = .007). Cognitive anxiety intensity was significantly lower post exercise in the practice condition compared to competition (P = .001). Cognitive anxiety direction showed greater debilitation post-exercise in the competition condition compared to practice (P = .01). Somatic anxiety intensity increased from pre-, to mid- to post-exercise (P = .001) irrespective of condition. This study suggests that badminton serve performance is negatively affected when physiological arousal, via badminton-specific exercise, and cognitive anxiety, via perceived competition, are high. PMID- 27412039 TI - Progression of Idiopathic Eruptive Macular Pigmentation in a Girl from Childhood to Adolescence: Case Report and Literature Review. AB - A 14-year-old girl developed brownish round macules and patches over the face, trunk, and proximal limbs with extensive progression since she was 7 years old. Electron microscopy examination revealed an increase in the number and maturity of melanosomes in basal and suprabasal keratinocytes, although the number of melanocytes was within the normal range. A diagnosis of idiopathic eruptive macular pigmentation was made. We describe the unusual disease progression of this case of idiopathic eruptive macular pigmentation, which was thought to be self-limited. PMID- 27412038 TI - Survival rates of cancer patients with and without rheumatic disease: a retrospective cohort analysis. AB - BACKGROUND: To compare the outcomes of gastric, colon, lung, and breast cancer patients with and without rheumatic diseases (RD). METHODS: This retrospective study compared the cancer survival rates of a cohort of 122 cancer patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM/PM), or systemic sclerosis with that of a cohort of 366 age-, sex-, and, cancer type-matched patients without RD who received medical care from 2000 to 2014. Staging, comorbidities, and functional status were ascertained. Survival was compared using the Kaplan-Meier method. Relative risk of death was estimated as a hazard ratio (HR) using Cox regression analysis. RESULTS: The mean age of the RD patients at the time of cancer diagnosis was 58.7 +/- 11.5 years. The overall survival rate of gastric cancer patients did not differ between the cohorts. The survival of lung or breast cancer was worse in patients with RA or DM/PM than in those without RD (all, p < 0.05). After adjusting for cancer stage, comorbidity index, performance status and age at the time of cancer diagnosis (as well as interstitial lung disease for lung cancer group), the mortality rate among lung cancer patients with RA was significantly higher (HR, 1.81; 95 % CI, 1.03-3.18) than that of lung cancer patients without RD, whereas SSc was associated with decreased mortality of lung cancer (HR, 0.16; 95 % CI, 0.04-0.58). DM/PM were associated with increased mortality of breast cancer patients (HR, 297.39; 95 % CI, 4.24-20842.33). CONCLUSIONS: RA and DM/PM seemed to be associated with a higher mortality in patients with lung or breast cancers, whereas SSc seemed to be associated with decreased mortality in patients with lung cancer. It is warranted to explore the survival effect of tailored cancer treatments according to specific RD. PMID- 27412040 TI - Measurement of BCR-ABL1 transcripts on the International Scale in the United States: current status and best practices. AB - Chronic myeloid leukemia (CML) results from the Philadelphia chromosome (Ph) translocation and expression of its fusion oncoprotein BCR-ABL1. BCR-ABL1 tyrosine kinase inhibitors (TKIs) are the standard therapy for Ph-positive CML. Achievement of deep molecular responses (typically defined as >=4-log reduction in BCR-ABL1 RNA levels) is an emerging treatment goal becoming attainable for more patients due to the availability of second-generation TKIs. Deep molecular responses are associated with improved long-term outcomes and are required prior to attempting cessation of treatment in treatment-free remission clinical trials. The National Comprehensive Cancer Network and European LeukemiaNet recommend regular monitoring of BCR-ABL1 RNA levels using real-time quantitative polymerase chain reaction (RQ-PCR). However, BCR-ABL1 RQ-PCR is a complex laboratory developed test; routine quantitative results from clinical diagnostic laboratories may differ from those used to establish the recommendations. Although an International Scale (IS) was developed for standardized reporting of BCR-ABL1 RNA levels, IS adoption has been slow in the United States, but is now used by the vast majority of laboratories. Here, we discuss the importance of molecular monitoring in CML, gaps between current and best molecular monitoring practices in the United States, and challenges and potential solutions for universal IS adoption in the United States. PMID- 27412041 TI - Causes of cancellations on the day of surgery at a Tertiary Teaching Hospital. AB - BACKGROUND: Cancellation of elective scheduled operations on the day of surgery leads to an inefficient use of operating room (OR) time and a waste of resources. It also causes inconvenience for patients and families. Moreover, day of surgery (DOS) cancellation creates logistic and financial burden associated with extended hospital stay and repetitions of pre-operative preparations as well as opportunity costs of lost time and missed income. The objective of this study is to establish the rate of elective surgical cases cancellations on the day of surgery and the reasons for these cancellations stratified by avoidable versus unavoidable within a tertiary care teaching hospital in Beirut, Lebanon as well as recommend appropriate solutions. METHOD: This is a prospective audit of the operation theatre list over a period of eight months (January 1, 2013-August 30, 2013). All patients scheduled to undergo elective surgeries at the hospital from January-August 2013 were included. An assigned OR staff recorded the cancelled cases in real time. The assigned staff confirmed the cancellation reason and added additional explanation if necessary by calling patients or through direct inquiry of clerical and/or clinical staff the following day. A Pareto chart was constructed to prioritize the reasons that accounted for 80 % of the avoidable surgical cancellations. RESULTS: For the given study period, 5929 elective surgeries were performed, of which 261 cases (4.4 %) were cancelled on the day of surgery. 187 cases (or 71.6 %) were judged as potentially avoidable cancellations versus 74 (28.4 %) that were judged as unavoidable. Of the 187 potentially avoidable cancellations, lack of financial clearance, incomplete medical evaluation, patient not showing up for surgery, and OR behind schedule accounted for almost 80 % of the causes. CONCLUSION: This study showed that the majority of cancellations were deemed avoidable and hospital related. A day of surgery cancellation rate less than 2 % is attainable. Determining the major avoidable contributors to DOS cancellations is an essential first step to developing appropriate interventions to improve operating theater efficiency. Recommended interventions were presented accordingly. PMID- 27412042 TI - Gastric Cancer: Nanoparticles as Tools to Improve Treatment Efficacy. AB - In recent years, advances in nanotechnology have raised the specter of developing effective agents for the treatment of high-impact diseases, like gastric cancer, which remains one of the major causes of cancer deaths worldwide. This article reviews advances in the treatment of this pathology using several types of nanoparticles. First, we start with an overview of gastric cancer, its prevention, detection and the available treatments. Then, we discuss nanotechnology-based novel strategies using polymeric nanosystems, nanovesicular systems and inorganic nanoparticles. All of these systems are being evaluated in the perspective of improving the targeting of anticancer drugs and reducing their negative side effects. PMID- 27412043 TI - What do I need to know about penicillin antibiotics? AB - The penicillins remain the class of antibiotics most commonly prescribed to children worldwide. In an era when the risks posed by antimicrobial resistance are growing, an understanding of antibiotic pharmacology and how to apply these principles in clinical practice is increasingly important. This paper provides an overview of the pharmacology of penicillins, focusing on those aspects of pharmacokinetics, pharmacodynamics and toxicity that are clinically relevant in paediatric prescribing. Penicillin allergy is frequently reported but a detailed history of suspected adverse reactions is essential to identify whether a clinically relevant hypersensitivity reaction is likely or not. The importance of additional factors such as antibiotic palatability, concordance and stewardship are also discussed, highlighting their relevance to optimal prescribing of the penicillins for children. PMID- 27412044 TI - Fifteen-minute consultation: safety assessment prior to discharge of patient admitted for self-harm. AB - Paediatricians often admit young people who have self-harmed, as advised by the National Institute for Health and Care Excellence guidelines. A full psychosocial assessment is essential to understand the underlying needs and risks. In this paper we focus on what the discharging doctor needs to know to arrange for a safe discharge. This involves reviewing the admission notes for red flags. We also give advice on the verbal and non-verbal communication skills needed to contain both the doctor's and the patient's difficult feelings. PMID- 27412045 TI - Pregnancies in older women-it's time to adopt an 'every woman, every time' approach to preconception care. PMID- 27412046 TI - Rhodium(III)-Catalyzed Tandem [2+2+2] Annulation-Lactamization of Anilides with Two Alkynoates via Cleavage of Two Adjacent C-H or C-H/C-O bonds. AB - An electron-deficient Cp(E) rhodium(III) complex bearing a cyclopentadienyl ligand with two ethyl ester substituents catalyzes the tandem [2+2+2] annulation lactamization of acetanilides with two alkynoates via cleavage of adjacent two C H bonds to give densely substituted benzo[cd]indolones. The reactions of meta methoxy-substituted acetanilides with two alkynoates also provided benzo[cd]indolones via cleavage of adjacent C-H/C-O bonds. Furthermore, 3,5 dimethoxyacetanilides reacted with two alkynoates to give dearomatized spiro compounds. PMID- 27412047 TI - Dynamic apical surface rings in superficial layer cells of koi Cyprinus carpio scale epidermis. AB - This study examined the novel ring-shaped structures found in the apical surface of individual cells of the scale epidermis of koi Cyprinus carpio. These apical rings are highly dynamic structures with lifetimes ranging from a few to several minutes. While several ring forms were observed, the predominant ring morphology is circular or oval. Two distinct ring forms were identified and designated type I and type II. Type I rings have a well-defined outer border that encircles the surface microridges. Type II rings are smooth-surfaced, dinner-plate-like structures with membranous folds or compressed microridges in the centre. Type II rings appear less frequently than type I rings. Type I rings form spontaneously, arising from swollen or physically interrupted microridges but without initially perturbing the encircled microridges. After persisting for up to several minutes the ring closes in a centripetal movement to form a circular or irregular-shaped structure, the terminal disc. The terminal disc eventually disappears, leaving behind a submembranous vesicle-like structure, the terminal body. Type I rings can undergo multiple cycles of formation and closing. Recycling epidermal apical rings form through centrifugal expansion from the terminal disc followed by apparent contraction back to the disc structure, whereupon the cycle may repeat or cease. The findings demonstrate a novel skin surface structure in fishes and are discussed with respect to communication with the external aqueous environment. PMID- 27412048 TI - Nurse and midwifery education and intimate partner violence: a scoping review. AB - AIMS AND OBJECTIVES: This scoping review aims to identify the scope of current literature considering nurse/midwife educational practices in the areas of intimate partner violence to inform future nursing/midwifery educational policy and practice. BACKGROUND: Intimate partner violence is a global issue affecting a significant portion of the community. Healthcare professionals including nurses/midwives in hospital- and community-based environments are likely to encounter affected women and need educational strategies that support best practice and promote positive outcomes for abused women and their families. DESIGN: Scoping review of relevant literature from January 2000 to July 2015. METHOD: Search of databases: CINHAL, MEDLINE, EMBASE, PROQUEST Central and COCHRANE Library. Reference lists from included articles were searched for relevant literature as were several grey literature sources. RESULTS: This review demonstrates low levels of undergraduate or postregistration intimate partner violence education for nursing/midwifery staff and students. Existing intimate partner violence education strategies are varied in implementation, method and content. Outcomes of these educational programmes are not always rigorously evaluated for staff or client-based outcomes. CONCLUSIONS: Further research is needed to evaluate existing intimate partner violence education programmes for nurses/midwives and identify the most effective strategies to promote improved clinical practice and outcomes for abused women and their families. RELEVANCE TO CLINICAL PRACTICE: Intimate partner violence has a significant social and public health impact. The World Health Organization has identified the need to ensure that healthcare professionals are adequately trained to meet the needs of abused women. Intimate partner violence education programmes, commencing at undergraduate studies for nurses/midwives, need to be implemented with rigorously evaluated programmes to ensure they meet identified objectives, promote best practice and improve care for abused women. PMID- 27412049 TI - Ions switch off darkness: role of TPC2 in melanosomes. PMID- 27412050 TI - Zwitterionic chitosan for the systemic treatment of sepsis. AB - Severe sepsis and septic shock are life-threatening conditions, with Gram negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cationic charge, the very properties responsible for their interactions with LPS. We hypothesize that a chitosan derivative zwitterionic chitosan (ZWC), previously shown to suppress the production of pro-inflammatory cellular mediators in LPS challenged macrophages, will have protective effects in an animal model of sepsis induced by systemic injection of LPS. In this study, we evaluate whether ZWC attenuates the fatal effect of LPS in C57BL/6 mice and investigate the mechanism by which ZWC counteracts the LPS effect using a PMJ2-PC peritoneal macrophage cell line. Unlike its parent compound with low water solubility, intraperitoneally administered ZWC is readily absorbed with no local residue or adverse tissue reaction at the injection site. Whether administered at or prior to the LPS challenge, ZWC more than doubles the animals' median survival time. ZWC appears to protect the LPS-challenged organisms by forming a complex with LPS and thus attenuating pro-inflammatory signaling pathways. These findings suggest that ZWC have utility as a systemic anti-LPS agent. PMID- 27412053 TI - The absence of a gap state and enhancement of the Mars-van Krevelen reaction on oxygen defective Cu/CeO2 surfaces. AB - We report a detailed first-principles analysis of the electronic structures of oxygen defective CeO2 and Cu/CeO2 surfaces aimed at elucidating the disappearance of the gap state of defective CeO2 when a Cu atom is added at the surface. The top of the valence band of Cu/CeO2 originates from the O 2p states around this Cu atom. We show that this redistribution of electronic states at the defective Cu/CeO2 surface enhances the reactivity of the surface O atoms. Indeed, dynamical simulations show an acceleration of catalytic NO oxidation occurring via the Mars van Krevelen mechanism mediated by these highly reactive oxygens. PMID- 27412051 TI - Human Thanatomicrobiome Succession and Time Since Death. AB - The thanatomicrobiome (thanatos, Greek for death) is a relatively new term and is the study of the microbes colonizing the internal organs and orifices after death. Recent scientific breakthroughs in an initial study of the thanatomicrobiome have revealed that a majority of the microbes within the human body are the obligate anaerobes, Clostridium spp., in the internal postmortem microbial communities. We hypothesized that time-dependent changes in the thanatomicrobiome within internal organs can estimate the time of death as a human body decays. Here we report a cross-sectional study of the sampling of 27 human corpses from criminal cases with postmortem intervals between 3.5-240 hours. The impetus for examining microbial communities in different internal organs is to address the paucity of empirical data on thanatomicrobiomic succession caused by the limited access to these organs prior to death and a dearth of knowledge regarding the movement of microbes within remains. Our sequencing results of 16S rRNA gene amplicons of 27 postmortem samples from cadavers demonstrated statistically significant time-, organ-, and sex-dependent changes. These results suggest that comprehensive knowledge of the number and abundance of each organ's signature microorganisms could be useful to forensic microbiologists as a new source of data for estimating postmortem interval. PMID- 27412052 TI - Probing the electrical switching of a memristive optical antenna by STEM EELS. AB - The scaling of active photonic devices to deep-submicron length scales has been hampered by the fundamental diffraction limit and the absence of materials with sufficiently strong electro-optic effects. Plasmonics is providing new opportunities to circumvent this challenge. Here we provide evidence for a solid state electro-optical switching mechanism that can operate in the visible spectral range with an active volume of less than (5 nm)(3) or ~10(-6) lambda(3), comparable to the size of the smallest electronic components. The switching mechanism relies on electrochemically displacing metal atoms inside the nanometre scale gap to electrically connect two crossed metallic wires forming a cross point junction. These junctions afford extreme light concentration and display singular optical behaviour upon formation of a conductive channel. The active tuning of plasmonic antennas attached to such junctions is analysed using a combination of electrical and optical measurements as well as electron energy loss spectroscopy in a scanning transmission electron microscope. PMID- 27412054 TI - High-Sensitivity Troponin Assays: Boon or Bane for the Cardiologist? PMID- 27412055 TI - Validity of a Revised Short Form-12 Health Survey Version 2 in Different Ethnic Populations. AB - INTRODUCTION: The Short Form-12 version 2 (SF-12v2) is a shorter version of the Short Form-36 version 2 (SF-36v2) for assessing health-related quality of life. As the SF-12v2 could not be resolved into the physical- and mental-component summary score (PCS and MCS, respectively) in the general population of Singapore, this study aims to determine and validate the Singapore SF-12 version 2 (SG 12v2). MATERIALS AND METHODS: The SG- 12v2 was generated using the same methodology as the SF-12v2. Bootstrap analysis was used to determine if the SG 12v2 were significantly different from the SF-12v2. Content validity was assessed using percentage of variance (R2) of the Singapore version of SF-36v2 PCS and MCS explained by the SG-12v2 items. Agreement between the SF-36v2 and the SG-12v2 was assessed using Bland-Altman diagrams. Criterion validity was demonstrated if effect size differences between SF-36v2 and SG-12v2 were small (Cohen's criteria). Known-group validity of SG-12v2 was reported for participants with and without chronic diseases. RESULTS: Five items differed between the SG-12v2 and SF 12v2. Bootstrap analysis confirmed that SG-12v2 and SF-12v2 were significantly different. The SG12v2 explained 94% and 79% of the R2 of the SF-36v2 PCS and MCS, respectively. Agreement was good and effect size differences were small (<0.3). Participants with chronic diseases reported lower SG-12v2 scores compared to participants without chronic diseases. CONCLUSION: The SG-12v2 offers advantage over the SF-12v2 for use in the general population of Singapore. The SG-12v2 is a valid measure and will be particularly useful for large population health surveys in Singapore. PMID- 27412056 TI - The Use of Parenteral Nutrition Support in an Acute Care Hospital and the Cost Implications of Short-term Parenteral Nutrition. AB - INTRODUCTION: Parenteral nutrition (PN) is indicated for patients who are unable to progress to oral or enteral nutrition. There are no local studies done on estimating the cost of PN in acute settings. The aims of this study are to describe the demographics, costs of PN and manpower required; and to determine the avoidable PN costs for patients and hospital on short-term PN. MATERIALS AND METHODS: Patient data between October 2011 and December 2013 were reviewed. Data collected include demographics, length of stay (LOS), and the indication/duration of PN. PN administration cost was based on the cost of the PN bags, blood tests and miscellaneous items, adjusted to subsidy levels. Manpower costs were based on the average hourly rate. RESULTS: Costs for PN and manpower were approximately S$1.2 million for 2791 PN days. Thirty-six cases (18.8%) of 140 PN days were short-term and considered to be avoidable where patients progressed to oral/enteral diet within 5 days. These short-term cases totalled $59,154.42, where $42,183.15 was payable by the patients. The daily costs for PN is also significantly higher for patients on short-term PN (P <0.001). CONCLUSION: In our acute hospital, 90% of patients referred for PN were surgical patients. Majority of the cost comes from the direct daily cost of the bag and blood tests, while extensive manpower cost was borne by the hospital; 18.8% of our cohort had short term avoidable PN. Daily PN may cost up to 60% more in patients receiving short term PN. Clinicians should assess patient's suitability for oral/enteral feeding to limit the use of short-term PN. PMID- 27412058 TI - Aortic Dilatation at Different Levels of the Ascending Aorta in Patients with Bicuspid Aortic Valve. AB - INTRODUCTION: Bicuspid aortic valve (BAV) is the most common form of adult congenital heart disease. When compared to patients with a normal trileaflet aortic valve, dilatation of the aortic root and the ascending aorta (Asc Ao) are the common findings in patients with BAV, with consequent higher risk of developing aortic aneurysm, aortic dissection and rupture. We aim to determine the site of the Asc Ao where maximum dilatation occurs in Asian adult patients with BAV. MATERIALS AND METHODS: All subjects underwent full echocardiography examination. The diameter of the Asc Ao was measured at 3 cm, 4 cm, 5 cm, 6 cm and 7 cm from the level of aortic annulus to the Asc Ao in 2D from the parasternal long-axis view. RESULTS: A total of 80 patients (male/female: 45/35; mean age: 45.3 +/- 16.2 years) with congenital BAV and 30 normal control group (male/female: 16/14; mean age: 45.9 +/- 15.1 years) were enrolled. The indexed diameters of the Asc Ao were significantly larger than the control group. In patients with BAV, maximum dilatation of Asc Ao occurred around 6 cm distal to the aortic annulus. CONCLUSION: In patients with BAV, dilatation of Asc Ao is maximal at the mid Asc Ao region around 6 cm distal to the aorta annulus. PMID- 27412057 TI - In Vitro Efficacy of Six Alternative Antibiotics against Multidrug Resistant Escherichia Coli and Klebsiella Pneumoniae from Urinary Tract Infections. AB - INTRODUCTION: Increasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens. MATERIALS AND METHODS: Minimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction. RESULTS: Temocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates. CONCLUSION: This study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity. PMID- 27412059 TI - Comparison of Outcomes and Costs of Transcatheter Therapeutic Intervention and Surgical Ligation for the Treatment of Patent Ductus Arteriosus. PMID- 27412060 TI - Sequential Localised Neuropathic Itch Following Drastic Weight Gain and Loss. PMID- 27412061 TI - Perioperative Outcomes of Therapeutic Breast Surgery in the Elderly. PMID- 27412062 TI - A 40-Year-Old Man with Rashes and Palpitations. PMID- 27412063 TI - Inflamed Bipedal Nodules with a Distant Occult Cause. PMID- 27412064 TI - Gay guys using gay language: friendship, shared values and the intent-context effect matrix. AB - This article draws on in-depth interviews with 35 openly gay male undergraduates from four universities in England to develop an understanding of the changing nature of language related to homosexuality. In addition to finding a diminution in the prevalence of homophobic language, we demonstrate that participants maintain complex and nuanced understandings of phrases that do not use homophobic pejoratives, such as 'that's so gay'. The majority of participants rejected the notion that these phrases are inherently homophobic, instead arguing that the intent with which they are said and the context in which they are used are vital in understanding their meaning and effect. We conceptualize an intent-context effect matrix to understand the interdependency of these variables. Highlighting the situated nature of this matrix, we also demonstrate the importance of the existence of shared norms between those saying and hearing the phrase when interpreting such language. PMID- 27412065 TI - Spotlights on our sister journals: Chem. Eur. J. 30/2016. PMID- 27412068 TI - Neonatal imitation in context: Sensorimotor development in the perinatal period. AB - More than 35 years ago, Meltzoff and Moore (1977) published their famous article, "Imitation of facial and manual gestures by human neonates." Their central conclusion, that neonates can imitate, was and continues to be controversial. Here, we focus on an often-neglected aspect of this debate, namely, neonatal spontaneous behaviors themselves. We present a case study of a paradigmatic orofacial "gesture," namely tongue protrusion and retraction (TP/R). Against the background of new research on mammalian aerodigestive development, we ask: How does the human aerodigestive system develop, and what role does TP/R play in the neonate's emerging system of aerodigestion? We show that mammalian aerodigestion develops in two phases: (1) from the onset of isolated orofacial movements in utero to the postnatal mastery of suckling at 4 months after birth; and (2) thereafter, from preparation to the mastery of mastication and deglutition of solid foods. Like other orofacial stereotypies, TP/R emerges in the first phase and vanishes prior to the second. Based upon recent advances in activity-driven early neural development, we suggest a sequence of three developmental events in which TP/R might participate: the acquisition of tongue control, the integration of the central pattern generator (CPG) for TP/R with other aerodigestive CPGs, and the formation of connections within the cortical maps of S1 and M1. If correct, orofacial stereotypies are crucial to the maturation of aerodigestion in the neonatal period but also unlikely to co-occur with imitative behavior. PMID- 27412066 TI - The cytosolic cochaperone Sti1 is relevant for mitochondrial biogenesis and morphology. AB - Most mitochondrial proteins are synthesized in the cytosol prior to their import into the organelle. It is commonly accepted that cytosolic factors are required for delivering precursor proteins to the mitochondrial surface and for keeping newly synthesized proteins in an import-competent conformation. However, the identity of such factors and their defined contribution to the import process are mostly unknown. Using a presequence-containing model protein and a site-directed photo-crosslinking approach in yeast cells we identified the cytosolic chaperones Hsp70 (Ssa1) and Hsp90 (Hsp82) as well as their cochaperones, Sti1 and Ydj1, as putative cytosolic factors involved in mitochondrial protein import. Deletion of STI1 caused both alterations in mitochondrial morphology and lower steady-state levels of a subset of mitochondrial proteins. In addition, double deletion of STI1 with the mitochondrial import factors, MIM1 or TOM20, showed a synthetic growth phenotype indicating a genetic interaction of STI1 with these genes. Moreover, recombinant cytosolic domains of the import receptors Tom20 and Tom70 were able to bind in vitro Sti1 and other cytosolic factors. In summary, our observations point to a, direct or indirect, role of Sti1 for mitochondrial functionality. PMID- 27412069 TI - Everolimus in the treatment of neuroendocrine tumors of the respiratory and gastroenteropancreatic systems. AB - Neuroendocrine tumors (NETs) are a rare diverse group of malignancies occurring most commonly in the gastroenteropancreatic system and the lungs. The incidence of NETs is increasing worldwide; median survival for patients with metastatic NETs is 5-65 months. A growing body of evidence shows survival benefit in patients with advanced NETs (gastroenteropancreatic and lung) treated with mTOR inhibitor everolimus, with improvement in survival being demonstrated in the clinical trial and real-world setting. Everolimus has been shown to have a manageable safety profile, with the most common adverse events being stomatitis, rash, diarrhea, fatigue and infections. Due to the rarity of the condition, there are challenges in conducting clinical trials in these patients. Further research is required to clarify the role of adjuvant therapy, treatment sequencing and the use of multimodality treatments. PMID- 27412070 TI - Men increase contributions to a public good when under sexual competition. AB - Why humans cooperate in large groups and with non-kin remains a puzzle for researchers across the natural and social sciences. Investigating whether cooperation is sexually selected could contribute to an understanding of the evolution of human cooperation. Competition for access to mates could indeed select for cooperation. Using controlled laboratory experiments, we analyse whether and how the sex composition of a social environment, testosterone level, and relationship status affect contributions to a public good. The results show that variation in sex composition alters the amount of money that single men (but not men in a couple or women) contribute to a public good. Notably, in line with the competitive helping hypothesis, awareness of the presence of a woman leads to larger contributions by single men, most likely by triggering their competitiveness to be the most cooperative man in the group. However, we find no link between basal testosterone level and cooperativeness. We argue that men, notably single men, adopt cooperative behaviours as a signalling strategy in the context of mate choice and hence that cooperation is partly sexually selected. Our findings highlight the need to consider sexual selection as an additional mechanism for cooperation. PMID- 27412071 TI - Longitudinal course of depressive symptoms and anxiety after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Symptoms of anxiety and depression are present in almost half of the patients who survive an aneurysmal subarachnoid hemorrhage (aSAH), but the long term course is unknown. AIM: To study the longitudinal course and predictors of symptoms of anxiety and depression after aSAH. DESIGN: Prospective longitudinal study with test occasions at 3 months (baseline), 1 year (T2) and 2-5 years (T3) post-aSAH. SETTING: SAH outpatient clinic. POPULATION: One hundred forty-three patients visiting the outpatient clinic. METHODS: Patients visiting our outpatient clinic 3 months after aSAH and living independently in the community completed the Beck Depression Inventory-II-NL and the State-Trait Anxiety Inventory at 3 months (T1), one year (T2) and 2-5 years (T3). Potential predictors were collected at T1. RESULTS: Complete datasets from 93 patients were analyzed. Depressive symptoms were present in 39% (T1), 41% (T2) and 54% (T3) of patients, symptoms of anxiety in 52% (T1), 48% (T2) and 53% (T3). Of patients with depressive symptoms at T1, 72% still had symptoms at T3, compared to 67% for anxiety. Disability on the Glasgow Outcome Scale (GOS), passive coping (UCL-PR) and depressive symptoms at T1 were significantly independent variables explaining 52% of the variance of depressive symptoms at T2. GOS and UCL-PR at T1 were variables explaining 25% of the variance of depressive symptoms at T3. Depressive symptoms and anxiety at T1 were predictive variables for anxiety at T2 (explained variance 43%) and UCL-PR for anxiety at T3 (explained variance 21%). CONCLUSIONS: The prevalence of symptoms of depression and anxiety remained high during the first 2-5 years after aSAH. Passive coping at 3 months after aSAH was the most consistent predictor of symptoms of anxiety and depression in the long term. CLINICAL REHABILITATION IMPACT: Since many patients who are initially free of symptoms of depression and anxiety develop such symptoms over time, we advocate screening for these symptoms and coping strategies to identify these patients and apply targeted therapy. PMID- 27412072 TI - Language features in the acute phase of poststroke severe aphasia could predict the outcome. AB - BACKGROUND: Aphasia recovery remains difficult to predict initially in particular for the most severe cases. The features of impaired verbal communication which are the basis for cognitive-linguistic diagnosis and treatment could be part of prediction of recovery from aphasia. AIM: This study investigated whether some components of language screening in the acute phase of stroke are reliable prognostic factors for language recovery in the post-acute phase. DESIGN: Monocentric prospective study. SETTING: University hospital stroke unit. POPULATION: Eighty-six patients aged between 21 and 92 years (mean=67.4, SD=15.3) were admitted after a first left hemisphere stroke with aphasia and were consecutively included. METHODS: Language assessment was performed in the acute phase and 3 months post-stroke with the LAnguage Screening Test (LAST) and the Aphasia Severity Rating Scale (ASRS) of the Boston Diagnostic Aphasia Examination (BDAE). Severe aphasia was defined as ASRS<3. Good recovery was defined as an ASRS>=4. Language scores and other potential predictors of recovery were analysed by comparing groups of patients with good versus poor recovery and as predictors of change with multiple regression approaches. RESULTS: LAST Total score as well as all the individual items of LAST, NIHSS and ASRS measured in the acute phase significantly differentiated good and poor recovery from aphasia at three months for all aphasic patients and for the most severe cases. In multivariable analyses the repetition score of LAST at the acute phase was significantly associated with the delta of ASRS between the acute phase and 3 months after the stroke reflecting changes in symptom severity. CONCLUSIONS: For patients with initial severe aphasia, word repetition from a language screening task seems to be a more relevant predictor of recovery than initial severity to enrich the prognosis of poststroke aphasia recovery three month after a stroke. These findings show the importance of phonological perception and production as well as speech motor components in the recovery of language. These linguistic aspects of the assessment seem more relevant than severity for prediction in the acute phase. CLINICAL REHABILITATION IMPACT: These findings could improve aphasia management pathway for people with severe aphasia and their families and minimize the evidence-practice gap for speech pathologists. PMID- 27412073 TI - Evidence based position paper on physical and rehabilitation medicine (PRM) practice for people with spinal deformities during growth. The European PRM position (UEMS PRM Section). AB - INTRODUCTION: Scoliosis and other spinal deformities involve 3-4% of the population during growth. Their so-called conservative treatment is in the field of competence of physical and rehabilitation medicine (PRM) physicians. This evidence based position paper represents the official position of the European Union through the European Union of Medical Specialists (UEMS) - PRM Section. The aim of the paper was to improve PRM specialists' professional practice for patients with spinal deformities during growth. EVIDENCE ACQUISITION: A systematic review of the literature and a Consensus procedure with 26 recommendations by means of a Delphi method process has been performed involving the delegates of all European countries represented in the UEMS-PRM Section. EVIDENCE SYNTHESIS: the systematic literature review is reported together with 26 recommendations coming from the Consensus Delphi procedure. CONCLUSIONS: The professional role of PRM physicians in spinal deformities during growth is to propose a complete PRM treatment for the patients considering all the concurring diseases and pathologies, impairments, activity limitations and participation restrictions. The PRM physician's role is to coordinate the individual PRM project developed in team with other health professionals and medical specialists, in agreement with the patient and his family, according to the specific medical diagnoses. PMID- 27412074 TI - Correlation between subclinical hypothyroidism and renal function in patients with diabetes mellitus. AB - AIM: To evaluate the incidence of and risk factors for subclinical hypothyroidism (SCH) in patients with type 2 diabetes mellitus (T2D), and determine the association of SCH with renal function. METHODS: T2D patients hospitalized between June 2007 and July 2008 were cross-section ally assessed. Clinical indicators and renal function were compared between the SCH and normal thyroid function groups. Risk factors for SCH and diabetic renal injury (albuminuria) were evaluated by univariate and multivariate analyses. RESULTS: Subclinical hypothyroidism prevalence was significantly higher in women, with a male to female ratio of 1:2.7. Age (62.56 +/- 10.79 vs. 59.09 +/- 10.82 years, P = 0.008), systolic blood pressure (138.80 +/- 18.85 vs. 131.29 +/- 16.97, P = 0.000), TC (5.22 +/- 1.20 vs. 4.83 +/- 1.03 mmol/L; P = 0.008), LDL-C (3.35 +/- 0.96 vs. 3.06 +/- 0.87 mmol/L; P = 0.007), creatinine (84.54 +/- 47.05 vs. 74.49 +/- 29.96 umol/L; P = 0.01), urinary albumin excretion rate [18.6 (7.58-326.78) vs. 10.69 (5.79-40.8) ug/min; P = 0.001], and thyrotropin [4.92 (4.37-6.27) vs. 1.4 (0.92-2.09) MUIU/mL; P = 0.000] were significantly higher in the SCH group; meanwhile, TBIL (12.05 +/- 5.20 vs. 13.98 +/- 5.32 umol/L; P = 0.008), DBIL (2.54 +/- 1.20 vs. 2.88 +/- 1.17 umol/L; P = 0.033), IDBIL (9.51 +/- 4.62 vs. 11.10 +/- 4.72 umol/L; P = 0.013), and total glomerular filtration rate [46.96 (35-68.26) vs. 71.74 (50.13-83.36) mL/min; P = 0.000] were significantly lower in SCH patients. Macroalbuminuria prevalence was significantly higher in the SCH group (18.2 vs. 11.4%; P < 0.001). Interestingly, SBP (OR = 1.050; 95%CI 1.034-1.066; P = 0.000), DR (OR = 5.248; 95%CI 2.816-9.777; P = 0.000), SCH (OR = 2.256; 95%CI 1.184-4.299; P = 0.013), and TC (OR = 1.389; 95%CI 1.108-1.742; P = 0.004) were found to be independent risk factors for macroalbuminuria. CONCLUSION: These findings demonstrate an association of SCH with renal injury in diabetic patients. PMID- 27412075 TI - N-Heterocyclic Carbene Ligands for Au Nanocrystal Stabilization and Three Dimensional Self-Assembly. AB - N-Heterocyclic carbenes (NHCs) have emerged as a new class of ligands for materials chemistry that appears particularly relevant for the stabilization and functionalization of metal nanoparticles (NPs). The particular properties and high synthetic flexibility of NHCs make them highly attractive tools for the development of new (nano)materials and the fundamental study of their properties. The relationships between the NHC structure and NP structure/properties, including physical, biological, and self-assembly properties, remain largely unknown. In the past decade, many efforts have been made to gain more fundamental understanding in this area. In this feature article, we present our contribution in this field focusing on the formation of NHC-coated Au nanocrystals (NCs), their stability, and their ability to self-assemble into 3D crystalline structures called supracrystals. First, the formation of NHC-stabilized Au NCs is discussed by comparing different NHC structures, NHC-based Au precursors, and synthesis methods. This study shows the major role of the NHC structure in obtaining both stable NHC-coated Au NCs and narrow size distributions. In a second part, a comparative study of the oxygen resistance of NHC- and thiol coated NCs is presented, demonstrating the enhanced stability of NHC-coated Au NCs to oxygen-based treatments. Finally, the self-assembly of NHC-coated Au NCs into 3D Au superlattices is presented. The formation of large organized domains of several micrometers is described from the design of NHCs tailored with long alkyl chains. In these different contexts, efforts have been made to gain a more in-depth understanding of the behavior of NHC ligands at the surface of NCs. These results show that the NHC-based approach to nanomaterials has many assets for opening a new research area in the supracrystal world. PMID- 27412077 TI - Anaphylaxis to IVIG. AB - Anaphylactic reactions are a known complication in some IgA-deficient patients receiving blood or plasma transfusions. It is of particular interest that anaphylaxis has been observed in patients with common variable immunodeficiency (CVID) who are receiving intravenous gammaglobulin (IVIG), and in that, although these patients have an impaired response to common vaccines, they retain the ability to produce autoantibodies. In this study, we review IgA antibodies (both IgG- and IgE-mediated reactions) in patients with CVID and hypogammaglobulinemia, anaphylaxis in antibody immunodeficient patients receiving IVIG, and proposed mechanisms of desensitization and prevention of anaphylactic reactions in immunodeficient patients receiving IVIG. We summarize and assess the 23 case reports documented in the literature that have described anaphylactic reactions in immunodeficient patients receiving IVIG since 1962 until currently, and make a comparison of their immunoglobulin levels, IgG anti-IgA, IgE anti-IgA, concentration of IVIG, IgA content in IVIG, method used to detect antibodies, length of treatment, and any subsequent tolerated treatment documented. PMID- 27412078 TI - Templated growth of gold satellites on dimpled silica cores. AB - We synthesize robust clusters of gold satellites positioned with tetrahedral symmetry on the surface of a patchy silica core by adsorption and growth of gold on the patches. First we conduct emulsion polymerization of styrene in the presence of 52 nm silica seeds whose surface has been modified with methacryloxymethyltriethoxysilane (MMS). We derive four-dimple particles from the resulting silica/polystyrene tetrapods. Polystyrene chains are covalently bound to the silica surface within the dimples due to the MMS grafts and they may be thiolated to induce adsorption of 12 nm gold particles. Using chloroauric acid, ascorbic acid and sodium citrate at room temperature, we grow gold from these 12 nm seeds without detachment from or deformation of the dimpled silica surface. We obtain gold satellites of tunable diameter up to 140 nm. PMID- 27412079 TI - Editor's Note. PMID- 27412076 TI - Antagonizing Retinoic Acid Receptors Increases Myeloid Cell Production by Cultured Human Hematopoietic Stem Cells. AB - Activities of the retinoic acid receptor (RAR)alpha and RARgamma are important to hematopoiesis. Here, we have investigated the effects of receptor selective agonists and antagonists on the primitive human hematopoietic cell lines KG1 and NB-4 and purified normal human hematopoietic stem cells (HSCs). Agonizing RARalpha (by AGN195183) was effective in driving neutrophil differentiation of NB 4 cells and this agonist synergized with a low amount (10 nM) of 1alpha,25 dihydroxyvitamin D3 to drive monocyte differentiation of NB-4 and KG1 cells. Treatment of cultures of human HSCs (supplemented with stem cell factor +/- interleukin 3) with an antagonist of all RARs (AGN194310) or of RARalpha (AGN196996) prolonged the lifespan of cultures, up to 55 days, and increased the production of neutrophils and monocytes. Slowing down of cell differentiation was not observed, and instead, hematopoietic stem and progenitor cells had expanded in number. Antagonism of RARgamma (by AGN205728) did not affect cultures of HSCs. Studies of CV-1 and LNCaP cells transfected with RAR expression vectors and a reporter vector revealed that RARgamma and RARbeta are activated by sub-nM all trans retinoic acid (EC50-0.3 nM): ~50-fold more is required for activation of RARalpha (EC50-16 nM). These findings further support the notion that the balance of expression and activity of RARalpha and RARgamma are important to hematopoietic stem and progenitor cell expansion and differentiation. PMID- 27412080 TI - L-proline: a highly effective cryoprotectant for mouse oocyte vitrification. AB - Recent studies have shown that L-proline is a natural osmoprotectant and an antioxidant to protect cells from injuries such as that caused by freezing and thawing in many species including plant, ram sperm and human endothelial cells. Nevertheless, this nontoxic cryoprotectant has not yet been applied to mammalian oocyte vitrification. In this study we evaluated the efficiency and safety of the new cryoprotectant in oocyte vitrification. The results indicated that L-proline improves the survival rate of vitrified oocytes, protects mitochondrial functions and could be applied as a new cryoprotectant in mouse oocyte vitrification. PMID- 27412081 TI - Effect of Bacillus spp. direct-fed microbial on slurry characteristics and gaseous emissions in growing pigs fed with high fibre-based diets. AB - A 26-day trial with 18 Pietrain*(Landrace*Duroc) pigs was conducted to investigate the effect of two dose levels of a specifically selected Bacillus spp. direct-fed microbial (DFM) product, on the emission of environmentally harmful gasses (methane, ammonia and hydrogen sulphide) from manure. Pigs were assigned to one of three treatments in a randomized complete block design according to their sex and initial BW. Each treatment contained three replications with two pigs per pen. The test treatments included a Bacillus spp. DFM containing 3*108 colony-forming unit/g, added at a low (250 mg/kg) and high (500 mg/kg) dose to an antibiotic free high fibre-based diet, and a non supplemented control diet. Manure from pigs fed with the supplemented diets emitted lower amounts of atmospheric contaminants. The most significant reduction was observed with low DFM supplementation, in which methane and ammonia volatilization decreased (P40% and 50%, respectively, on fresh weight basis in relation to the control. Microbiome analysis of manure by high through put sequencing techniques on eubacterial and archaeal 16S rRNA genes highlighted the complex interactions between indigenous gut microflora and inoculated Bacillus spp. The tested Bacillus DFM could be considered as a best available technique in reducing the environmental impacts of growing pigs fed with high fibre-based diets. PMID- 27412082 TI - Radiography on wheels arrives to nursing homes - an economic assessment of a new health care technology in southern Sweden. AB - RATIONALE, AIMS AND OBJECTIVES: The process of transferring older, vulnerable adults from an elder care facility to the hospital for medical care can be an emotionally and physically stressful experience. The recent development of modern mobile radiography may help to ease this anxiety by allowing for evaluation in the nursing home itself. Up until this point, no health economic evaluation of the technology has been attempted in a Swedish setting. The objective of this study was to determine whether examinations of patients in elder care facilities with mobile radiography were cost-effective from a societal perspective compared with hospital-based radiological examinations. METHODS: This prospective study included two groups of nursing home residents in two different areas in southern Sweden. All residents in the nursing homes were targeted for the study. Seventy one patients were examined with hospital-based radiography at two hospitals, and 312 patients were examined using mobile radiography in nursing homes. Given that the diagnostic effects are regarded as equivalent, a cost minimization method was applied. Direct costs were estimated using prices from the county council, Region Skane, Sweden. RESULTS: From a societal perspective, mobile radiography was shown to have significantly lower costs per examination compared with hospital-based radiography. The difference in health care-related costs was also significant in favour of mobile radiography. CONCLUSION: Mobile radiography can be used to examine patients in nursing homes at a lower cost than hospital-based radiography. Patients benefit from not having to transfer to a hospital for radiography, resulting in reduced anxiety for patients. PMID- 27412083 TI - Quantitative assessment of chemotherapy-induced peripheral neurotoxicity using a point-of-care nerve conduction device. AB - Chemotherapy-induced peripheral neurotoxicity (CIPN) seriously impairs patients' quality of life cumulatively and dose-dependently. Because assessment of CIPN usually depends on patients' subjective evaluation of symptoms, objective and quantitative measures are needed. We evaluated a point-of-care nerve conduction device (POCD), previously validated for the assessment of diabetic peripheral neuropathy. Sensory nerve action potential (SNAP) amplitude and sensory nerve conduction velocity (SNCV) of the sural nerve were measured using a portable, automated POCD (DPNCheck; NeuroMetrix Inc., Waltham, MA, USA) in patients with a clinical diagnosis of CIPN of grade 1 or higher. We compared SNAP and SNCV among patients with different grades of CIPN according to the Common Terminology Criteria for Adverse Events. A total of 50 patients (22 men, 28 women; median age, 64 years; grade 1/2/3, 21/18/11) were evaluated. Anticancer drugs responsible for CIPN were cisplatin in five patients, oxaliplatin in 15, carboplatin in 5, paclitaxel in 16, docetaxel in 14, nab-paclitaxel in 7, vincristine in 6, and bortezomib in 3. Unadjusted SNAP was 8.45 +/- 3.67 MUV (mean +/- SD) in patients with grade 1 CIPN, 5.42 +/- 2.68 MUV with grade 2, and 2.45 +/- 1.52 MUV with grade 3. Unadjusted SNCV was 49.71 +/- 4.77 m/s in patients with grade 1 CIPN, 48.78 +/- 6.33 m/s with grade 2, and 44.14 +/- 7.31 m/s with grade 3. The adjusted SNAP after controlling for age significantly differed between each CTCAE grade (P < 0.001, ancova). The adjusted SNCV after controlling for age and height also differed significantly (P = 0.027). Differences in the severity of CIPN could be detected objectively and quantitatively using this POCD. PMID- 27412084 TI - Tunable superomniphobic surfaces for sorting droplets by surface tension. AB - We utilized tunable superomniphobic surfaces with flower-like TiO2 nanostructures to fabricate a simple device with precisely tailored surface energy domains that, for the first time, can sort droplets by surface tension. We envision that our methodology for droplet sorting will enable inexpensive and energy-efficient analytical devices for personalized point-of-care diagnostic platforms, lab-on-a chip systems, biochemical assays and biosensors. PMID- 27412085 TI - Investigation into the presence of human papillomavirus in patients with obstructive sleep apnea. AB - OBJECTIVES/HYPOTHESIS: The human papillomavirus (HPV) is known to infect the tissues of the oropharynx as demonstrated in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV has also been shown to induce benign lymphoid hypertrophy. We sought to investigate an association between obstructive sleep apnea (OSA) and the presence of HPV in palatine and lingual tonsillar oropharyngeal tissue. STUDY DESIGN: Case series with chart review. METHODS: This retrospective laboratory-based study of oropharyngeal tissue from patients with OSA included patients >18 years old who underwent surgical treatment for OSA at a single institution between January 2012 and May 2014. Surgical specimens of adequate size were analyzed for HPV6, 11, and 16 using real-time quantitative polymerase chain reaction from DNA extracted from formalin-fixed paraffin embedded tissue blocks. Student t test, Pearson chi2 test, and linear logistic regression were used to assess comparisons of body mass index (BMI), apnea hypopnea index (AHI), age, and gender between HPV-positive and HPV-negative groups. RESULTS: Of 99 cases included in the study, six were positive for HPV: two with HPV16 and four with HPV6. BMI, AHI, age, and gender showed no significant differences between the HPV-positive and HPV-negative groups. Logistic regression to predict HPV positivity accounting for each variable and multivariate analysis were not statistically significant. CONCLUSIONS: Our study did not show HPV to have a statistically significant association with OSA. None of the covariates analyzed (BMI, AHI, gender, age) predicted HPV positivity in surgically resected oropharyngeal tissue from OSA patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1231-1234, 2017. PMID- 27412086 TI - MorphoLibJ: integrated library and plugins for mathematical morphology with ImageJ. AB - MOTIVATION: Mathematical morphology (MM) provides many powerful operators for processing 2D and 3D images. However, most MM plugins currently implemented for the popular ImageJ/Fiji platform are limited to the processing of 2D images. RESULTS: The MorphoLibJ library proposes a large collection of generic tools based on MM to process binary and grey-level 2D and 3D images, integrated into user-friendly plugins. We illustrate how MorphoLibJ can facilitate the exploitation of 3D images of plant tissues. AVAILABILITY AND IMPLEMENTATION: MorphoLibJ is freely available at http://imagej.net/MorphoLibJ CONTACT: david.legland@nantes.inra.frSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27412087 TI - sBWT: memory efficient implementation of the hardware-acceleration-friendly Schindler transform for the fast biological sequence mapping. AB - MOTIVATION: The Full-text index in Minute space (FM-index) derived from the Burrows-Wheeler transform (BWT) is broadly used for fast string matching in large genomes or a huge set of sequencing reads. Several graphic processing unit (GPU) accelerated aligners based on the FM-index have been proposed recently; however, the construction of the index is still handled by central processing unit (CPU), only parallelized in data level (e.g. by performing blockwise suffix sorting in GPU), or not scalable for large genomes. RESULTS: To fulfill the need for a more practical, hardware-parallelizable indexing and matching approach, we herein propose sBWT based on a BWT variant (i.e. Schindler transform) that can be built with highly simplified hardware-acceleration-friendly algorithms and still suffices accurate and fast string matching in repetitive references. In our tests, the implementation achieves significant speedups in indexing and searching compared with other BWT-based tools and can be applied to a variety of domains. AVAILABILITY AND IMPLEMENTATION: sBWT is implemented in C ++ with CPU-only and GPU-accelerated versions. sBWT is open-source software and is available at http://jhhung.github.io/sBWT/Supplementary information: Supplementary data are available at Bioinformatics online. CONTACT: chyee@ntu.edu.tw or jhhung@nctu.edu.tw (also juihunghung@gmail.com). PMID- 27412088 TI - cisASE: a likelihood-based method for detecting putative cis-regulated allele specific expression in RNA sequencing data. AB - MOTIVATION: Allele-specific expression (ASE) is a useful way to identify cis acting regulatory variation, which provides opportunities to develop new therapeutic strategies that activate beneficial alleles or silence mutated alleles at specific loci. However, multiple problems hinder the identification of ASE in next-generation sequencing (NGS) data. RESULTS: We developed cisASE, a likelihood-based method for detecting ASE on single nucleotide variant (SNV), exon and gene levels from sequencing data without requiring phasing or parental information. cisASE uses matched DNA-seq data to control technical bias and copy number variation (CNV) in putative cis-regulated ASE identification. Compared with state-of-the-art methods, cisASE exhibits significantly increased accuracy and speed. cisASE works moderately well for datasets without DNA-seq and thus is widely applicable. By applying cisASE to real datasets, we identified specific ASE characteristics in normal and cancer tissues, thus indicating that cisASE has potential for wide applications in cancer genomics. AVAILABILITY AND IMPLEMENTATION: cisASE is freely available at http://lifecenter.sgst.cn/cisASE CONTACT: biosinodx@gmail.com or yxli@sibs.ac.cnSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27412089 TI - MEMHDX: an interactive tool to expedite the statistical validation and visualization of large HDX-MS datasets. AB - MOTIVATION: With the continued improvement of requisite mass spectrometers and UHPLC systems, Hydrogen/Deuterium eXchange Mass Spectrometry (HDX-MS) workflows are rapidly evolving towards the investigation of more challenging biological systems, including large protein complexes and membrane proteins. The analysis of such extensive systems results in very large HDX-MS datasets for which specific analysis tools are required to speed up data validation and interpretation. RESULTS: We introduce a web application and a new R-package named 'MEMHDX' to help users analyze, validate and visualize large HDX-MS datasets. MEMHDX is composed of two elements. A statistical tool aids in the validation of the results by applying a mixed-effects model for each peptide, in each experimental condition, and at each time point, taking into account the time dependency of the HDX reaction and number of independent replicates. Two adjusted P-values are generated per peptide, one for the 'Change in dynamics' and one for the 'Magnitude of DeltaD', and are used to classify the data by means of a 'Logit' representation. A user-friendly interface developed with Shiny by RStudio facilitates the use of the package. This interactive tool allows the user to easily and rapidly validate, visualize and compare the relative deuterium incorporation on the amino acid sequence and 3D structure, providing both spatial and temporal information. AVAILABILITY AND IMPLEMENTATION: MEMHDX is freely available as a web tool at the project home page http://memhdx.c3bi.pasteur.fr CONTACT: marie-agnes.dillies@pasteur.fr or sebastien.brier@pasteur.frSupplementary information: Supplementary data is available at Bioinformatics online. PMID- 27412090 TI - BioPartsDB: a synthetic biology workflow web-application for education and research. AB - : Synthetic biology has become a widely used technology, and expanding applications in research, education and industry require progress tracking for team-based DNA synthesis projects. Although some vendors are beginning to supply multi-kilobase sequence-verified constructs, synthesis workflows starting with short oligos remain important for cost savings and pedagogical benefit. We developed BioPartsDB as an open source, extendable workflow management system for synthetic biology projects with entry points for oligos and larger DNA constructs and ending with sequence-verified clones. AVAILABILITY AND IMPLEMENTATION: BioPartsDB is released under the MIT license and available for download at https://github.com/baderzone/biopartsdb Additional documentation and video tutorials are available at https://github.com/baderzone/biopartsdb/wiki An Amazon Web Services image is available from the AWS Market Place (ami-a01d07c8). CONTACT: joel.bader@jhu.edu. PMID- 27412091 TI - VisualGraphX: interactive graph visualization within Galaxy. AB - MOTIVATION: We developed VisualGraphX, a web-based, interactive visualization tool for large-scale graphs. Current graph visualization tools that follow the rich-internet paradigm lack an interactive and scalable visualization of graph based data. VisualGraphX aims to provide a universal graph visualization tool that empowers the users to efficiently explore the data for themselves at a large scale. It is available as a visualization plugin for the Galaxy platform, such that VisualGraphX can be integrated into custom analysis pipelines. AVAILABILITY AND IMPLEMENTATION: VisualGraphX has been released as a visualization plugin for the Galaxy platform under AFL 3.0 and is available with instructions and application data at http://gitlab.com/comptrans/VisualGraphX/ CONTACT: bjoern.voss@ibvt.uni-stuttgart.de. PMID- 27412092 TI - LightAssembler: fast and memory-efficient assembly algorithm for high-throughput sequencing reads. AB - MOTIVATION: The deluge of current sequenced data has exceeded Moore's Law, more than doubling every 2 years since the next-generation sequencing (NGS) technologies were invented. Accordingly, we will able to generate more and more data with high speed at fixed cost, but lack the computational resources to store, process and analyze it. With error prone high throughput NGS reads and genomic repeats, the assembly graph contains massive amount of redundant nodes and branching edges. Most assembly pipelines require this large graph to reside in memory to start their workflows, which is intractable for mammalian genomes. Resource-efficient genome assemblers combine both the power of advanced computing techniques and innovative data structures to encode the assembly graph efficiently in a computer memory. RESULTS: LightAssembler is a lightweight assembly algorithm designed to be executed on a desktop machine. It uses a pair of cache oblivious Bloom filters, one holding a uniform sample of [Formula: see text]-spaced sequenced [Formula: see text]-mers and the other holding [Formula: see text]-mers classified as likely correct, using a simple statistical test. LightAssembler contains a light implementation of the graph traversal and simplification modules that achieves comparable assembly accuracy and contiguity to other competing tools. Our method reduces the memory usage by [Formula: see text] compared to the resource-efficient assemblers using benchmark datasets from GAGE and Assemblathon projects. While LightAssembler can be considered as a gap based sequence assembler, different gap sizes result in an almost constant assembly size and genome coverage. AVAILABILITY AND IMPLEMENTATION: https://github.com/SaraEl-Metwally/LightAssembler CONTACT: sarah_almetwally4@mans.edu.egSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27412093 TI - LAMPLINK: detection of statistically significant SNP combinations from GWAS data. AB - : One of the major issues in genome-wide association studies is to solve the missing heritability problem. While considering epistatic interactions among multiple SNPs may contribute to solving this problem, existing software cannot detect statistically significant high-order interactions. We propose software named LAMPLINK, which employs a cutting-edge method to enumerate statistically significant SNP combinations from genome-wide case-control data. LAMPLINK is implemented as a set of additional functions to PLINK, and hence existing procedures with PLINK can be applicable. Applied to the 1000 Genomes Project data, LAMPLINK detected a combination of five SNPs that are statistically significantly accumulated in the Japanese population. AVAILABILITY AND IMPLEMENTATION: LAMPLINK is available at http://a-terada.github.io/lamplink/ CONTACT: terada@cbms.k.u-tokyo.ac.jp or sese.jun@aist.go.jpSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27412094 TI - Estimating evolutionary rates using time-structured data: a general comparison of phylogenetic methods. AB - MOTIVATION: In rapidly evolving pathogens, including viruses and some bacteria, genetic change can accumulate over short time-frames. Accordingly, their sampling times can be used to calibrate molecular clocks, allowing estimation of evolutionary rates. Methods for estimating rates from time-structured data vary in how they treat phylogenetic uncertainty and rate variation among lineages. We compiled 81 virus data sets and estimated nucleotide substitution rates using root-to-tip regression, least-squares dating and Bayesian inference. RESULTS: Although estimates from these three methods were often congruent, this largely relied on the choice of clock model. In particular, relaxed-clock models tended to produce higher rate estimates than methods that assume constant rates. Discrepancies in rate estimates were also associated with high among-lineage rate variation, and phylogenetic and temporal clustering. These results provide insights into the factors that affect the reliability of rate estimates from time structured sequence data, emphasizing the importance of clock-model testing. CONTACT: sduchene@unimelb.edu.au or garzonsebastian@hotmail.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27412095 TI - SSBD: a database of quantitative data of spatiotemporal dynamics of biological phenomena. AB - MOTIVATION: Rapid advances in live-cell imaging analysis and mathematical modeling have produced a large amount of quantitative data on spatiotemporal dynamics of biological objects ranging from molecules to organisms. There is now a crucial need to bring these large amounts of quantitative biological dynamics data together centrally in a coherent and systematic manner. This will facilitate the reuse of this data for further analysis. RESULTS: We have developed the Systems Science of Biological Dynamics database (SSBD) to store and share quantitative biological dynamics data. SSBD currently provides 311 sets of quantitative data for single molecules, nuclei and whole organisms in a wide variety of model organisms from Escherichia coli to Mus musculus The data are provided in Biological Dynamics Markup Language format and also through a REST API. In addition, SSBD provides 188 sets of time-lapse microscopy images from which the quantitative data were obtained and software tools for data visualization and analysis. AVAILABILITY AND IMPLEMENTATION: SSBD is accessible at http://ssbd.qbic.riken.jp CONTACT: sonami@riken.jp. PMID- 27412096 TI - MSAViewer: interactive JavaScript visualization of multiple sequence alignments. AB - : The MSAViewer is a quick and easy visualization and analysis JavaScript component for Multiple Sequence Alignment data of any size. Core features include interactive navigation through the alignment, application of popular color schemes, sorting, selecting and filtering. The MSAViewer is 'web ready': written entirely in JavaScript, compatible with modern web browsers and does not require any specialized software. The MSAViewer is part of the BioJS collection of components. AVAILABILITY AND IMPLEMENTATION: The MSAViewer is released as open source software under the Boost Software License 1.0. Documentation, source code and the viewer are available at http://msa.biojs.net/Supplementary information: Supplementary data are available at Bioinformatics online. CONTACT: msa@bio.sh. PMID- 27412097 TI - A noise model for the evaluation of defect states in solar cells. AB - A theoretical model, combining trapping/detrapping and recombination mechanisms, is formulated to explain the origin of random current fluctuations in silicon based solar cells. In this framework, the comparison between dark and photo induced noise allows the determination of important electronic parameters of the defect states. A detailed analysis of the electric noise, at different temperatures and for different illumination levels, is reported for crystalline silicon-based solar cells, in the pristine form and after artificial degradation with high energy protons. The evolution of the dominating defect properties is studied through noise spectroscopy. PMID- 27412098 TI - The Influence of Donor and Recipient Gender Incompatibility on Corneal Transplant Rejection and Failure. AB - In vascularized organ transplants, gender mismatches have higher rates of immunological rejection. We investigated the influence of gender incompatibility, including H-Y incompatibility, on corneal transplant graft rejection and failure. Patients were included who had undergone a first corneal transplant for keratoconus (KC), Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK), infection and other indications. A Cox regression model was fitted for each indication to determine factors affecting graft failure and rejection at 5 years. The impact of gender, including H-Y, matching was analyzed after accounting for other factors, including known risk factors. Of 18 171 patients, 4314 had undergone a transplant for FED, 4783 for KC, 3669 for PBK, 1903 for infection and 3502 for other disorders. H-Y mismatched (male [M]->female [F]) corneas were at greater risk of graft failure or rejection. For FED, F->F were 40% less likely to fail (p < 0.0001) and 30% less likely to reject (p = 0.01); M->M were 20% less likely to fail (p = 0.04) and 30% less likely to reject (p = 0.01). For KC, M->M matched corneas were 30% less likely to fail (p = 0.05) and 20% less likely to reject (p = 0.01) compared with H-Y mismatches. H-Y antigen mismatched (M->F) patients were at greater risk of rejection or graft failure. PMID- 27412099 TI - Other side of the coin for personalised medicine and healthcare: content analysis of 'personalised' practices in the literature. AB - OBJECTIVES: Various terms and definitions are used to describe personalised approaches to medicine and healthcare, but in ambiguous and inconsistent ways. They mostly have been defined in a top-down manner. However, actual practices might take different paths. Here, we aimed to provide a 'practice-based' perspective on the debate by analysing the content of 'personalised' practices published in the literature. METHODS: The search in PubMed and EMBASE (April 2014) using the terms frequently used for personalised approaches resulted in 5333 records. 2 independent researchers used different strategies for screening, resulting in 157 articles describing 88 'personalised' practices that were implemented/presented on at least 1 individual/patient case. The content analysis was grounded on these data and did not have a priori analytical frameworks. RESULTS: 'Personalised medicine/healthcare' can be a commodity in the healthcare market, a way how health services are provided, or a keyword for emerging applications. It can help individuals/patients to gain control of their health, health professionals to provide better services, healthcare organisations to increase effectiveness and efficiency, or national health systems to increase performance. Country examples indicated that for integration of practices into health services, attitude towards innovations and health system and policy context is important. Categorisation based on the terms or the technologies used, if any, was not possible. CONCLUSIONS: This study is the first to provide a comprehensive content analysis of the 'personalised' practices in the literature. Unlike the top-down definitions, our findings highlighted not the technologies but real-life issues faced by the practices. 'Personalised medicine' and 'personalised healthcare' can be differentiated by using the former for specific tools available and the latter for health services with a holistic approach, implemented in certain contexts. To realise integration of 'personalised medicine/healthcare' into real life, science, technology, health policy and practice, and society domains must work together. PMID- 27412100 TI - Risk of epilepsy in stroke patients receiving acupuncture treatment: a nationwide retrospective matched-cohort study. AB - OBJECTIVE: To investigate the risk of epilepsy in stroke patients receiving and not receiving acupuncture treatment. DESIGN: Retrospective cohort study. SETTING: This study was based on Taiwan's National Health Insurance Research Database that included information on stroke patients hospitalised between 1 January 2000 and 31 December 2004. PARTICIPANTS: We identified 42 040 patients hospitalised with newly diagnosed stroke who were aged 20 years and above. PRIMARY AND SECONDARY OUTCOME MEASURES: We compared incident epilepsy during the follow-up period until the end of 2009 in stroke patients who were and were not receiving acupuncture. The adjusted HRs and 95% CIs of epilepsy associated with acupuncture were calculated using multivariate Cox proportional hazard regression. RESULTS: Stroke patients who received acupuncture treatment (9.8 per 1000 person-years) experienced a reduced incidence of epilepsy compared to those who did not receive acupuncture treatment (11.5 per 1000 person-years), with an HR of 0.74 (95% CI 0.68 to 0.80) after adjustment for sociodemographic factors and coexisting medical conditions. Acupuncture treatment was associated with a decreased risk of epilepsy, particularly among stroke patients aged 20-69 years. The log-rank test probability curve indicated that stroke patients receiving acupuncture treatment had a reduced probability of epilepsy compared with individuals who did not receive acupuncture treatment during the follow-up period (p<0.0001). CONCLUSIONS: Stroke patients who received acupuncture treatment had a reduced risk of epilepsy compared with those not receiving acupuncture treatment. However, the protective effects associated with acupuncture treatment require further validation in prospective cohort studies. PMID- 27412102 TI - Incidence, risk factors and the healthcare cost of falls postdischarge after elective total hip and total knee replacement surgery: protocol for a prospective observational cohort study. AB - INTRODUCTION: The number of major joint replacement procedures continues to increase in Australia. The primary aim of this study is to determine the incidence of falls in the first 12 months after discharge from hospital in a cohort of older patients who undergo elective total hip or total knee replacement. METHODS AND ANALYSES: A prospective longitudinal observational cohort study starting in July 2015, enrolling patients aged >=60 years who are admitted for elective major joint replacement (n=267 total hip replacement, n=267 total knee replacement) and are to be discharged to the community. Participants are followed up for 12 months after hospital discharge. The primary outcome measure is the rate of falls per thousand patient-days. Falls data will be collected by 2 methods: issuing a falls diary to each participant and telephoning participants monthly after discharge. Secondary outcomes include the rate of injurious falls and health-related quality of life. Patient-rated outcomes will be measured using the Oxford Hip or Oxford Knee score. Generalised linear mixed modelling will be used to examine the falls outcomes in the 12 months after discharge and to examine patient and clinical characteristics predictive of falls. An economic evaluation will be conducted to describe the nature of healthcare costs in the first 12 months after elective joint replacement and estimate costs directly attributable to fall events. ETHICS AND DISSEMINATION: The results will be disseminated through local site networks and will inform future services to support older people undergoing hip or knee joint replacement and also through peer-reviewed publications and medical conferences. This study has been approved by The University of Notre Dame Australia and local hospital human research ethics committees. TRIAL REGISTRATION NUMBER: ACTRN12615000653561; Pre-results. PMID- 27412101 TI - Impact of coronary collaterals on in-hospital and 5-year mortality after ST elevation myocardial infarction in the contemporary percutaneous coronary intervention era: a prospective observational study. AB - OBJECTIVES: To evaluate the short-term and long-term prognostic impacts of acute phase coronary collaterals to occluded infarct-related arteries (IRA) after ST elevation myocardial infarction (STEMI) in the percutaneous coronary intervention (PCI) era. DESIGN: A prospective observational study. SETTING: Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. PARTICIPANTS: 3340 patients with STEMI from the OACIS database who were admitted to hospitals within 24 hours from the onset and who had a completely occluded IRA. INTERVENTIONS: Patients were divided into 4 groups according to the Rentrop collateral score (RCS) by angiography on admission (RCS-0, no visible collaterals; RCS-1, collaterals without IRA filling; RCS-2, collaterals with partial IRA filling; and RCS-3, collaterals with complete IRA filling). PRIMARY OUTCOME MEASURES: In-hospital and 5-year mortality. RESULTS: Patients with RCS-0/3 were older than patients with RCS-1/2, and the prevalence of previous myocardial infarction was highest in patients with RCS-3. Median peak creatinine phosphokinase levels decreased as RCS increases (p<0.001), suggesting the acute cardioprotective effects of collaterals. Although RCS-1 and RCS-2 collaterals were associated with better in hospital mortality (adjusted OR 0.48, p=0.046 and 0.38, p=0.010 for RCS-1 and RCS 2, respectively) and 5-year mortality (adjusted HR 0.53, p=0.004 and 0.46, p<0.001 for RCS-1 and RCS-2, respectively) as compared with R-0, presence of RCS 3 collaterals was not associated with improved in-hospital (adjusted OR 1.35, p=0.331) and 5-year mortality (adjusted HR 0.98, p=0.920), possibly because worse clinical profiles in patients with RCS-3 may mask mortality benefit of coronary collaterals. CONCLUSIONS: Presence of acute phase coronary collaterals such as RCS-1 and RCS-2 were associated with better in-hospital and 5-year mortality after STEMI in the contemporary PCI era. PMID- 27412103 TI - COBA-Cohort: a prospective cohort of HIV-negative men who have sex with men, attending community-based HIV testing services in five European countries (a study protocol). AB - INTRODUCTION: Community-based voluntary counselling and testing (CBVCT) services for men who have sex with men (MSM) can reach those most-at-risk and provide an environment for gay men that is likely to be non-stigmatising. Longitudinal data on the behaviour of HIV-negative MSM are scarce in Europe. The aim of this protocol, developed during the Euro HIV Early Diagnosis And Treatment (EDAT) project, is to implement a multicentre community-based cohort of HIV-negative MSM attending 15 CBVCT services in 5 European countries. RESEARCH OBJECTIVES: (1) To describe the patterns of CBVCT use, (2) to estimate HIV incidence, and to identify determinants of (3) HIV seroconversion and (4) HIV and/or sexually transmitted infection (STI) test-seeking behaviour. METHODS AND ANALYSIS: All MSM aged 18 years or over and who had a negative HIV test result are invited to participate in the COmmunity-BAsed Cohort (COBA-Cohort). Study enrolment started in February 2015, and is due to continue for at least 12 months at each study site. Follow-up frequency depends on the testing recommendations in each country (at least 1 test per year). Sociodemographic data are collected at baseline; baseline and follow-up questionnaires both gather data on attitudes and perceptions, discrimination, HIV/STI testing history, sexual behaviour, condom use, and pre- and post-exposure prophylaxis. Descriptive, exploratory and multivariate analyses will be performed to address the main research objectives of this study, using appropriate statistical tests and models. These analyses will be performed on the whole cohort data and stratified by study site or country. ETHICS AND DISSEMINATION: The study was approved by the Public Health authorities of each country where the study is being implemented. Findings from the COBA-Cohort study will be summarised in a report to the European Commission, and in leaflets to be distributed to study participants. Articles and conference abstracts will be submitted to peer-reviewed journals and conferences. PMID- 27412104 TI - Linking e-health records, patient-reported symptoms and environmental exposure data to characterise and model COPD exacerbations: protocol for the COPE study. AB - INTRODUCTION: Relationships between exacerbations of chronic obstructive pulmonary disease (COPD) and environmental factors such as temperature, humidity and air pollution are not well characterised, due in part to oversimplification in the assignment of exposure estimates to individuals and populations. New developments in miniature environmental sensors mean that patients can now carry a personal air quality monitor for long periods of time as they go about their daily lives. This creates the potential for capturing a direct link between individual activities, environmental exposures and the health of patients with COPD. Direct associations then have the potential to be scaled up to population levels and tested using advanced human exposure models linked to electronic health records. METHODS AND ANALYSIS: This study has 5 stages: (1) development and deployment of personal air monitors; (2) recruitment and monitoring of a cohort of 160 patients with COPD for up to 6 months with recruitment of participants through the Clinical Practice Research Datalink (CPRD); (3) statistical associations between personal exposure with COPD-related health outcomes; (4) validation of a time-activity exposure model and (5) development of a COPD prediction model for London. ETHICS AND DISSEMINATION: The Research Ethics Committee for Camden and Islington has provided ethical approval for the conduct of the study. Approval has also been granted by National Health Service (NHS) Research and Development and the Independent Scientific Advisory Committee. The results of the study will be disseminated through appropriate conference presentations and peer-reviewed journals. PMID- 27412105 TI - Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting. AB - INTRODUCTION: Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. METHODS AND ANALYSIS: Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3-4 physiotherapists) and a focus group (n=6-8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). ETHICS AND DISSEMINATION: This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). TRIAL REGISTRATION NUMBER: ISRCTN84528320. PMID- 27412107 TI - Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study. AB - OBJECTIVES: To evaluate the impact of dietary sodium and potassium (Na-K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population. SETTING: Prospective cohort study. PARTICIPANTS: In the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non communicable Disease And its Trends in the Aged). Men and women aged 30-79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na-K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model. PRIMARY OUTCOME MEASURES: Mortality from total and subtypes of stroke, CVD and all causes. RESULTS: A total of 1938 deaths from all causes were observed over 176 926 person-years. Na-K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na-K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na-K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality. CONCLUSIONS: Dietary Na-K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population. PMID- 27412106 TI - Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses. AB - OBJECTIVE: To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. DATA SOURCES: A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health related outcomes published between 1996 and 2013. STUDY ELIGIBILITY CRITERIA: Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. OUTCOME MEASURES: Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. RESULTS: 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. CONCLUSIONS: This systematic review and series of meta analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living with HIV. PMID- 27412108 TI - Protocol for a randomised control trial of methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients (MOTION). AB - INTRODUCTION: Gastrointestinal dysmotility and constipation are common problems in intensive care patients. The majority of critical care patients are sedated with opioids to facilitate tolerance of endotracheal tubes and mechanical ventilation, which inhibit gastrointestinal motility and lead to adverse outcomes. Methylnaltrexone is a peripheral opioid antagonist that does not cross the blood-brain barrier and can reverse the peripheral side effects of opioids without affecting the desired central properties. This trial will investigate whether methylnaltrexone can reverse opioid-induced constipation and gastrointestinal dysmotility. METHODS: This is a single-centre, multisite, double blind, randomised, placebo-controlled trial. 84 patients will be recruited from 4 intensive care units (ICUs) within Imperial College Healthcare NHS Trust. Patients will receive intravenous methylnaltrexone or placebo on a daily basis if they are receiving opioid infusion to facilitate mechanical ventilation and have not opened their bowels for 48 hours. All patients will receive standard laxatives as per the clinical ICU bowel protocol prior to randomisation. The primary outcome of the trial will be time to significant rescue-free laxation following randomisation. Secondary outcomes will include tolerance of enteral feed, gastric residual volumes, incidence of pneumonia, blood stream and Clostridium difficile infection, and any reversal of central opioid effects. ETHICS AND DISSEMINATION: The trial protocol, the patient/legal representative information sheets and consent forms have been reviewed and approved by the Harrow Research Ethics Committee (REC Reference 14/LO/2004). An independent Trial Steering Committee and Data Monitoring Committee are in place, with patient representation. On completion, the trial results will be published in peer reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBER: 2014-004687-37; Pre-results. PMID- 27412109 TI - Cohort profile: the Finnish Medication and Alzheimer's disease (MEDALZ) study. AB - PURPOSE: The aim of the Medicine use and Alzheimer's disease (MEDALZ) study is to investigate the changes in medication and healthcare service use among persons with Alzheimer's disease (AD) and to evaluate the safety and effectiveness of medications in this group. This is important, because the number of persons with AD is rapidly growing and even though they are a particularly vulnerable patient group, the number of representative, large-scale studies with adequate follow-up time is limited. PARTICIPANTS: MEDALZ contains all residents of Finland who received a clinically verified diagnosis of AD between 2005 and 2011 and were community-dwelling at the time of diagnosis (N=70 719). The diagnosis is based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCS-ADRDA) and Diagnostic and Statistical Manual Fourth Edition (DSM-IV) criteria for Alzheimer's disease. The cohort contains socioeconomic data (education, occupational status and taxable income, 1972-2012) and causes of death (2005 2012), data from the prescription register (1995-2012), the special reimbursement register (1972-2012) and the hospital discharge register (1972-2012). Future updates are planned.The average age was 80.1 years (range 34.5-104.6 years). The majority of cohort (65.2%) was women. Currently, the average length of follow-up after AD diagnosis is 3.1 years and altogether 26 045 (36.8%) persons have died during the follow-up. FINDINGS: Altogether 53% of the cohort had used psychotropic drugs within 1 year after AD diagnoses. The initiation rate of for example, benzodiazepines and related drugs and antidepressants began to increase already before AD diagnosis. FUTURE PLANS: We are currently assessing if these, and other commonly used medications are related to adverse events such as death, hip fractures, head injuries and pneumonia. PMID- 27412110 TI - Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: From history to the interaction with the monoaminergic systems. AB - Parkinson's disease is the second most common neurodegenerative disorder, characterized by the manifestation of motor symptoms, which are mainly attributed to the degeneration of dopamine neurons in the pars compacta of substantia nigra. Based on advancements in the understanding of the pathophysiology of the disease, especially in animal models, the subthalamic nucleus has been pointed as a major target for deep brain stimulation in the treatment of motor symptoms, first developed in non-human primate and then successfully transfered to parkinsonian patients. Nevertheless, despite the focus on motor deficits, Parkinson's disease is also characterized by the manifestation of non-motor symptoms, which can be due to the additional degeneration of norepinephrine, serotonin and cholinergic systems. The pathophysiology of the non-motor symptoms is under studied and consequently not well treated. Furthermore, data from the literature about the impact of subthalamic deep brain stimulation on non-motor disorders are controversial and still under debate. Similarly, the risk of mood disorders post deep brain stimulation surgery remains also controversial. Here, we review the clinical and experimental data of this neurosurgical approach on motor and non motor behaviors and provide evidence for its interaction with the monoaminergic systems. PMID- 27412111 TI - Association of blood glucose level and hypertension in Elderly Chinese Subjects: a community based study. AB - BACKGROUND: There is a scarcity of epidemiological researches examining the relationship between blood pressure (BP) and glucose level among older adults. The objective of the current study was to investigate the association of high BP and glucose level in elderly Chinese. METHODS: A cross-sectional study of a population of 2092 Chinese individuals aged over 65 years was conducted. Multiple logistic analysis was used to explore the association between hypertension and hyperglycemia. Independent risk factors for systolic and diastolic BP were analyzed using stepwise linear regression. RESULTS: Subjects in impaired fasting glucose group (IFG) (n = 144) and diabetes (n = 346), as compared with normal fasting glucose (NFG) (n = 1277), had a significant higher risk for hypertension, with odds ratios (ORs) of 1.81 (95 % CI, 1.39-2.35) (P = 0.000) and 1.40 (95 % CI, 1.09-1.80) (P = 0.009), respectively. Higher fasting plasma glucose (FPG) levels in the normal range were still significantly associated with a higher prevalence of hypertension in both genders, with ORs of 1.24 (95 % CI, 0.85 1.80), R (2) = 0.114, P = 0.023 in men and 1.61 (95 % CI, 1.12-2.30), R (2) = 0.082, P = 0.010 in women, respectively, when compared with lower FPG. Linear regression analysis revealed FPG was an independent factor of systolic and diastolic BP. CONCLUSIONS: Our findings suggest that hyperglycemia as well as higher FPG within the normal range is associated with a higher prevalence of hypertension independent of other cardiovascular risk factors in elderly Chinese. Further studies are needed to explore the relationship between hyperglycemia and hypertension in a longitudinal setting. PMID- 27412112 TI - Combining different assays and chemical analysis to characterize the genotoxicity of waters impacted by textile discharges. AB - Waters receiving textile discharges can exhibit genotoxic and mutagenic activity, which has been related to the presence of dyes and aromatic amines as synthesis precursors or byproducts. The aim of this study was to identify dyes and aromatic amines in water samples impacted by textile discharges, and to evaluate the genotoxic responses of these samples using the Salmonella/microsome assay in strains TA98 and YG1041, and the Fpg-modified comet assay in the RTL-W1 fish cell line. The genotoxicity of river samples downstream of the discharge was greater than the upstream samples in both of the Ames tests. The Fpg-modified comet assay detected similar levels of DNA damage in the upstream and downstream samples. Mutagenicity was not detected with TA98, except for the Quilombo River samples, but when YG1041 was used as the tester strain mutagenicity was detected for all sites with a very different profile in upstream sites relative to the other sites. The mutagenic response strongly indicated that aromatic amines or dyes were contributing to the mutagenic activity downstream. The impact of textile discharges was also confirmed by chemical analysis, because the highest concentrations of azo dyes and aromatic amines were detected in the river downstream. This study shows the value of combining assays measuring complementary endpoints to better characterize the mutagenicity of environmental samples, with the advantage that this approach provides an indication of what classes of compounds are responsible for the effect. Environ. Mol. Mutagen. 57:559-571, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27412113 TI - Cardiac Rehabilitation for Aboriginal and Torres Strait Islander people in Western Australia. AB - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in Australia. Australian Aboriginal and Torres Strait Islander (Indigenous) people have higher levels of CVD compared with non-Indigenous people. Cardiac Rehabilitation (CR) is an evidence-based intervention that can assist with reducing subsequent cardiovascular events and rehospitalisation. Unfortunately, attendance rates at traditional CR programs, both globally and in Australia, are estimated to be as low as 10-30 % and Indigenous people are known to be particularly under-represented. An in-depth assessment was undertaken to investigate the provision of CR and secondary preveniton services in Western Australia (WA) with a focus on rural, remote and Indigenous populations. This paper reports on the findings for Indigenous people. METHODS: Cardiac rehabilitation and Aboriginal Medical Services (n = 38) were identified for interview through the Heart Foundation Directory of Western Australian Cardiac Rehabilitation and Secondary Prevention Services 2012. Semi-structured interviews with CR coordinators were conducted and included questions specific to Indigenous people. RESULTS: Interviews with coordinators from 34 CR services (10 rural, 12 remote, 12 metropolitan) were conducted. Identification of Indigenous status was reported by 65 % of coordinators; referral and attendance rates of Indigenous patients differed greatly across WA. Efforts to meet the cultural needs of Indigenous patients varied and included case management (32 %), specific educational materials (35 %), use of a buddy or mentoring system (27 %), and access to an Aboriginal Health Worker (71 %). Staff cultural awareness training was available for 97 % and CR guidelines were utilised by 77 % of services. CONCLUSION: The under-representation of Indigenous Australians participating in CR, as reported in the literature and more specifically in this study, mandates a concerted effort to improve services to better meet the needs of Indigenous patients with CVD as part of closing the gap in life expectancy. Improving access to culturally appropriate CR and secondary prevention in WA must be an important component of this effort given the high rates of premature cardiovascular disease affecting Indigenous people. Our findings also highlight the importance of good systematic data collection across services. Health pathways that ensure continuity of care and alternative methods of CR delivery with dedicated resources are needed. PMID- 27412114 TI - Factors associated with performing tuberculosis screening of HIV-positive patients in Ghana: LASSO-based predictor selection in a large public health data set. AB - BACKGROUND: The purpose of this study is to propose the Least Absolute Shrinkage and Selection Operators procedure (LASSO) as an alternative to conventional variable selection models, as it allows for easy interpretation and handles multicollinearities. We developed a model on the basis of LASSO-selected parameters in order to link associated demographical, socio-economical, clinical and immunological factors to performing tuberculosis screening in HIV-positive patients in Ghana. METHODS: Applying the LASSO method and multivariate logistic regression analysis on a large public health data set, we selected relevant predictors related to tuberculosis screening. RESULTS: One Thousand Ninety Five patients infected with HIV were enrolled into this study with 691 (63.2 %) of them having tuberculosis screening documented in their patient folders. Predictors found to be significantly associated with performance of tuberculosis screening can be classified into factors related to the clinician's perception of the clinical state, as well as those related to PLHIV's awareness. These factors include newly diagnosed HIV infections (n = 354 (32.42 %), aOR 1.84), current CD4+ T cell count (aOR 0.92), non-availability of HIV type (n = 787 (72.07 %), aOR 0.56), chronic cough (n = 32 (2.93 %), aOR 5.07), intake of co-trimoxazole (n = 271 (24.82 %), aOR 2.31), vitamin supplementation (n = 220 (20.15 %), aOR 2.64) as well as the use of mosquito bed nets (n = 613 (56.14 %), aOR 1.53). CONCLUSIONS: Accelerated TB screening among newly diagnosed HIV-patients indicates that application of the WHO screening form for intensifying tuberculosis case finding among HIV-positive individuals in resource-limited settings is increasingly adopted. However, screening for TB in PLHIV is still impacted by clinician's perception of patient's health state and PLHIV's health awareness. Education of staff, counselling of PLHIV and sufficient financing are needed for further improvement in implementation of TB screening for all PLHIV. The LASSO approach proved a convenient method for automatic variable selection in a large public health data set that requires efficient and fast algorithms. TRIALS REGISTRATION: ClinicalTrials.gov NCT01897909 (July 5, 2013). PMID- 27412115 TI - COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data. AB - BACKGROUND: Numerous case-control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (-765G > C), rs689466 (-1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. METHODS: We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. RESULTS: Finally 8 case-control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. CONCLUSION: Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association. PMID- 27412116 TI - Ammonium Increases TRPC1 Expression Via Cav-1/PTEN/AKT/GSK3beta Pathway. AB - Hyperammonemia occurring following acute liver failure is the primary cause of hepatic encephalopathy. In the brain, ammonium is catabolised by glutamine synthetase expressed exclusively in astroglia; ammonium overload impairs astroglial homeostatic systems. Previously, we had reported that chronic treatment with 3 mM ammonia increased expression of transient receptor potential canonic 1 (TRPC1) channels and Ca2+ release from intracellular Ca2+ stores (Liang et al. in Neurochem Res 39:2127-2135, 2014). Glycogen synthase kinase 3beta (GSK 3beta) has a key role in several astroglial signalling pathways and is known to be affected in various CNS diseases. We have studied the involvement of Cav 1/PTEN/AKT/GSK-3beta signalling system in regulation of TRPC1 gene expression by ammonium. Effects of chronic (1-5 days) treatment with ammonium chloride (ammonium), at pathologically relevant concentrations of 1-5 mM were investigated on primary cultures of mouse cerebral astrocytes. We quantified expression of caveolin-1 (Cav-1), membrane content of phosphatase and tensin homologue (PTEN), phosphorylation of AKT and GSK-3beta, and expression of TRPC1 channels. Ammonium significantly increased expression of Cav-1 mRNA and protein, mRNA of TRPC1 as well as membrane content of PTEN; conversely phosphorylation of AKT and GSK-3beta were significantly decreased. These changes were abolished following astrocytes treatment with siRNA specific to Cav-1, indicating the involvement of Cav 1/PTEN/PI3K/AKT pathway. Similar results were found in the brains of adult mice subjected to intraperitoneal injection of urease (a model for hyperammoniemia) for 1-5 days. In transgenic mice tagged with an astrocyte-specific or neurone specific markers (used for fluorescence-activated cell sorting of astrocytes vs. neurones) and treated with intraperitoneal injections of urease for 3 days, the Cav-1 gene mRNA expression was up-regulated in astrocytes, but not in neurones. The up-regulation of TRPC1 gene expression by ammonium was suppressed by GSK 3beta inhibitors, lithium salt and AR-A014418, suggesting that increase of GSK 3beta activity may play a role in ammonium-related pathologies. PMID- 27412118 TI - Filimonas aurantiibacter sp. nov., an orange-pigmented bacterium isolated from lake water and emended description of the genus Filimonas. AB - A Gram-stain-negative bacterium was isolated from Lake Michigan water. 16S rRNA gene sequence analysis revealed that strain 1458T had a sequence similarity to Filimonas lacunae YT21T, Sediminibacterium goheungense HME7863T, Parasegetibacter terrae SGM2-10T, Sediminibacterium ginsengisoli DCY13T, Terrimonas ferruginea DSM 30193T, Lacibacter cauensis NJ-8T, Flavihumibacter solisilvae 3-3T, Parasegetibacter luojieneis RHYL-37T, Vibrionimonas magnilacihabitans MU-2T and Parafilimonas terrae 5GHs7-2T with values of 93.4, 92.3, 91.9, 91.9, 91.8, 91.6, 91.6, 91.6, 91.5 and 90.4 %, respectively. The primary cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1G and summed feature 3 (iso-C15 : 0 2 OH/C16 : 1omega7c). The primary polar lipids were phosphatidylethanolamine and an unidentified polar lipid only detectable after total polar lipid staining. The quinone system was menaquinone MK-7, and in the polyamine pattern, sym homospermidine was predominant. Additional phenotypic characteristics included growth at 15 to 40 degrees C and pH 5.0 to 8.0, a salt tolerance range of 0 to 2.0 % (w/v), production of orange cell-bound pigment flexirubin, and gliding motility. After phenotypic, chemotaxonomic and molecular analyses, strain 1458T was identified as a novel species of the genus Filimonas, for which the name Filimonas aurantiibacter sp. nov. is proposed. The type strain is 1458T (=NRRL B 65305T=LMG 29039T). An emended description of the genus Filimonas is also provided. PMID- 27412117 TI - Amino Acid Promoieties Alter Valproic Acid Pharmacokinetics and Enable Extended Brain Exposure. AB - Valproic acid (VPA) has been used to treat epileptic seizures for decades, but it may also possess therapeutic potential in other nervous system diseases. However, VPA is extensively bound to plasma proteins, asymmetrically transported across the blood-brain barrier and metabolized to toxic species in the liver, which all contribute to its severe off-target adverse effects and possible drug-drug interactions. In this study, we evaluated seven amino acid prodrugs of VPA that were targeted to utilize L-type amino acid transporter 1 (LAT1), if they could alter the brain uptake mechanism and systemic pharmacokinetics of VPA. All prodrugs had affinity for LAT1 studied as competitive inhibition of [14C]-L leucine in human breast cancer (MCF-7) cell line. However, since the ester prodrugs were unstable they were not studied further, instead the corresponding amide prodrugs were used to evaluate their systemic pharmacokinetics in rats and the uptake mechanism via LAT1 into the rat brain. All amide prodrugs were bound to a lesser extent to plasma proteins than VPA and this being independent of the prodrug concentration. Amide prodrugs were also delivered into the brain after intravenous bolus injection. One of the prodrug showed greater brain uptake and high selectivity for LAT1 and it was able to release VPA slowly within the brain. Therefore, it was concluded that the VPA brain concentrations can be stabilized as well as the problematic pharmacokinetic profile can be altered by a LAT1 selective prodrug. PMID- 27412119 TI - Ultrafast decoherence dynamics govern photocarrier generation efficiencies in polymer solar cells. AB - All-organic-based photovoltaic solar cells have attracted considerable attention because of their low-cost processing and short energy payback time. In such systems the primary dissociation of an optical excitation into a pair of photocarriers has been recently shown to be extremely rapid and efficient, but the physical reason for this remains unclear. Here, two-dimensional photocurrent excitation spectroscopy, a novel non-linear optical spectroscopy, is used to probe the ultrafast coherent decay of photoexcitations into charge-producing states in a polymer:fullerene based solar cell. The two-dimensional photocurrent spectra are interpreted by introducing a theoretical model for the description of the coupling of the electronic states of the system to an external environment and to the applied laser fields. The experimental data show no cross-peaks in the twodimensional photocurrent spectra, as predicted by the model for coherence times between the exciton and the photocurrent producing states of 20 fs or less. PMID- 27412120 TI - Clinical Use of Continuous Performance Tests to Diagnose Children With ADHD. AB - OBJECTIVE: This study evaluated the diagnostic application of continuous performance tests in children with ADHD. METHOD: We recruited 114 children (aged 6-12) from August 2012 to May 2014. Seventy-nine children were diagnosed with ADHD and 35 were enrolled as controls. The Advanced Test of Attention (ATA) was administered to all participants. RESULTS: There were significant between-group differences for the frequency distribution of four ATA variables. The ATA criteria yielded a diagnostic sensitivity and specificity of 84.8% and 45.7%, respectively. Discriminant analysis revealed that auditory reaction time variability and visual commission errors helped distinguish between the groups. Discriminate functions indicated correct classification of 64.9% children. ADHD children tended to have lower intra-class correlation coefficients. CONCLUSION: Our results suggest that the ATA distributions of ADHD individuals may differ from the general population; in addition, the ATA results could not independently diagnose ADHD. Therefore, they should be considered carefully before diagnosis. PMID- 27412122 TI - Atezolizumab: First Global Approval. AB - Atezolizumab (TecentriqTM)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma. PMID- 27412121 TI - Daptomycin Pharmacokinetics and Pharmacodynamics in Septic and Critically Ill Patients. AB - Infections, including sepsis, are associated with high mortality rates in critically ill patients in the intensive care unit (ICU). Appropriate antibiotic selection and adequate dosing are important for improving patient outcomes. Daptomycin is bactericidal in bloodstream infections caused by Staphylococcus aureus and other Gram-positive pathogens cultured in ICU patients. The drug has concentration-dependent activity, and the area under the curve/minimum inhibitory concentration ratio is the pharmacokinetic/pharmacodynamic (PK/PD) index that best correlates with daptomycin activity, whereas toxicity correlates well with daptomycin plasma trough concentrations (or minimum concentration [C min]). Adequate daptomycin exposure can be difficult to achieve in ICU patients; multiple PK alterations can result in highly variable plasma concentrations, which are difficult to predict. For this reason, therapeutic drug monitoring could help clinicians optimize daptomycin dosing, thus improving efficacy while decreasing the likelihood of serious adverse events. This paper reviews the literature on daptomycin in ICU patients with sepsis, focusing on dosing and PK and PD parameters. PMID- 27412123 TI - Characteristics of learning curve in minimally invasive ileal pouch-anal anastomosis in a single institution. AB - BACKGROUND: Previous work from our institution has characterized the learning curve for open ileal pouch-anal anastomosis (IPAA). The purpose of the present study was to assess the learning curve of minimally invasive IPAA. METHODS: Perioperative outcomes of 372 minimally invasive IPAA by 20 surgeons (10 high volume vs. 10 low-volume surgeons) during 2002-2013, included in a prospectively maintained database, were assessed. Predicted outcome models were constructed using perioperative variables selected by stepwise logistic regression, using Akaike's information criterion. Cumulative sums (CUSUM) of differences between observed and predicted outcomes were graphed over time to identify possible improvement patterns. RESULTS: Institutional pelvic sepsis and other pouch morbidity rates (hemorrhage, anastomotic separation, pouch failure, fistula) significantly decreased (18.2 vs. 7.0 %, CUSUM peak after 143 cases, p = 0.001; 18.4 vs. 5.3 %, CUSUM peak after 239 cases, respectively, p < 0.001). Institutional total proctocolectomy mean operative times significantly decreased (307 min vs. 253 min, CUSUM peak after 84 cases, p < 0.001), unlike completion proctectomy (p = 0.093) or conversion rates (10 vs. 5.4 %, p = 0.235). Similar learning curves were identified among high-volume surgeons but not among low volume surgeons. Learning curves were identified in the two busiest individual surgeons for pelvic sepsis (peaks at 47 and 9 cases, p = 0.045 and p = 0.002) and in one surgeon for operative times (CUSUM peak after 16 and 13 cases for both total proctocolectomy and completion proctectomy (p < 0.001 and p = 0.006) but not for other pouch complications (peak at 49 and 41 cases, p = 0.199 and p = 0.094). CONCLUSION: Pouch complications, particularly pelvic sepsis, are the most consistent and relevant learning curve end points in laparoscopic IPAA. PMID- 27412124 TI - National disparities in minimally invasive surgery for pancreatic tumors. AB - BACKGROUND: For patients with pancreatic tumors, several disparities have been shown to impact access to care, including surgery, and subsequently adversely affect long-term oncologic outcomes. The aim of this study was to investigate national disparities in minimally invasive surgery (MIS) across different demographics for pancreatic tumors. METHODS: We utilized the American College of Surgeons (ACS) National Cancer Data Base (NCDB) to identify patients with pancreatic tumors from 2010 to 2011 who had undergone surgery through either an open or MIS approach. Multivariable analysis was performed to investigate differences in patient characteristics in relation to surgical approach and conversion to open. RESULTS: A total of 2809 patients were identified. The initial surgical approach included 86.5 % open (2430) and 13.5 % MIS (87.6 % were laparoscopic, and 12.4 % were robotic). Tumor histology was significantly associated with MIS, whereby patients with neuroendocrine tumors were more than twice as likely to have an MIS approach compared to adenocarcinoma. Tumor location within the pancreas was also associated with MIS, with tumors in the tail being three times more likely to be removed through MIS compared to tumors in the head. For patients with disease in the body or tail of the pancreas, ethnicity was independently associated with MIS whereby patients of Hispanic origin were less likely to have MIS. The conversion rate to open was 27.7 %, and geographic location was associated with conversion rates. CONCLUSIONS: MIS procedures comprise approximately 13.5 % of surgical procedures for pancreatic tumors. In addition to tumor histology, differences in surgical approach were identified with respect to ethnicity for patients with tumors in the body/tail of the pancreas. PMID- 27412125 TI - Measuring intra-operative decision-making during laparoscopic cholecystectomy: validity evidence for a novel interactive Web-based assessment tool. AB - BACKGROUND: Errors in judgment during laparoscopic cholecystectomy can lead to bile duct injuries and other complications. Despite correlations between outcomes, expertise and advanced cognitive skills, current methods to evaluate these skills remain subjective, rater- and situation-dependent and non systematic. The purpose of this study was to develop objective metrics using a Web-based platform and to obtain validity evidence for their assessment of decision-making during laparoscopic cholecystectomy. METHODS: An interactive online learning platform was developed ( www.thinklikeasurgeon.com ). Trainees and surgeons from six institutions completed a 12-item assessment, developed based on a cognitive task analysis. Five items required subjects to draw their answer on the surgical field, and accuracy scores were calculated based on an algorithm derived from experts' responses ("visual concordance test", VCT). Test retest reliability, internal consistency, and correlation with self-reported experience, Global Operative Assessment of Laparoscopic Skills (GOALS) score and Objective Performance Rating Scale (OPRS) score were calculated. Questionnaires were administered to evaluate the platform's usability, feasibility and educational value. RESULTS: Thirty-nine subjects (17 surgeons, 22 trainees) participated. There was high test-retest reliability (intraclass correlation coefficient = 0.95; n = 10) and internal consistency (Cronbach's alpha = 0.87). The assessment demonstrated significant differences between novices, intermediates and experts in total score (p < 0.01) and VCT score (p < 0.01). There was high correlation between total case number and total score (rho = 0.83, p < 0.01) and between total case number and VCT (rho = 0.82, p < 0.01), and moderate to high correlations between total score and GOALS (rho = 0.66, p = 0.05), VCT and GOALS (rho = 0.83, p < 0.01), total score and OPRS (rho = 0.67, p = 0.04), and VCT and OPRS (rho = 0.78, p = 0.01). Most subjects agreed or strongly agreed that the platform and assessment was easy to use [n = 29 (78 %)], facilitates learning intra-operative decision-making [n = 28 (81 %)], and should be integrated into surgical training [n = 28 (76 %)]. CONCLUSION: This study provides preliminary validity evidence for a novel interactive platform to objectively assess decision-making during laparoscopic cholecystectomy. PMID- 27412126 TI - Are single or dual luminal covered expandable metallic stents suitable for esophageal squamous cell carcinoma with esophago-airway fistula? AB - BACKGROUND: To analyze the outcomes of single or dual luminal self-expandable covered metallic stents (SECMS) for palliative treatment for esophageal cancer with esophago-airway fistula (EAF). METHODS: We retrospectively assessed 50 patients who underwent SECMS placement for malignant EAF at our institution between June 2005 and December 2014 to define clinical results of stenting. Treatment provided was classified into initial single airway, single esophageal, or double stent placement. Independent associations between size, location of the EAF, patient's condition, and the risk of migration or reopening with the different types of stenting were examined using logistic regression analysis. RESULTS: The final management of malignant EAF was esophageal stent in 21 patients, airway stent in 13, and dual stents in 16. No patients failed stenting. During a median follow-up of 178 days (range 1-893 days), the fistula reopened in 33 (66 %) of 50 patients. No factors, including fistula size, location, or initial selection of single or dual stenting, were correlated with reopening. Nineteen (57.6 %) of 33 patients needed restenting, and the reopened EAF was sealed off successfully in 52.6 % of new stent placements. The clinical failure of EAF closure was correlated only with proximal dilated esophagus (p = 0.013). Mean survival in patients with clinical success of EAF closure was also significantly longer than that in patients with clinical failure (242.0 vs. 80.1 days, p < 0.001). KPS (p = 0.026), cough ability (p = 0.004), successful closure of EAF (p = 0.001), and reopening (p = 0.007) all had significant effects on survival. CONCLUSIONS: We conclude that SECMS is safe and effective in the palliation of esophageal cancer with malignant EAF, especially in patients with an otherwise excellent general condition. Other modalities of management are recommended for malignant EAF with proximal dilation of the esophagus. PMID- 27412127 TI - How many samples would be optimal for endobronchial cryobiopsy? AB - BACKGROUND: Cryobiopsy, which provides larger specimens without crush artifact, is a good option for the diagnosis of visible endobronchial tumors. While there are several papers on diagnostic performance, application protocols vary between centers. In this study, we aimed to find the optimal number of cryobiopsies in endobronchial tumors. METHODS: We prospectively involved cases with a visible endobronchial tumor in which conventional diagnostic measures failed and/or a therapeutic interventional bronchoscopy was planned. Endobronchial tumor was visualized, and four cryobiopsies were taken with a dedicated flexible probe. The samples were evaluated by a pathologist who was blinded to the order of the biopsies. The cumulative performances of one to four cryobiopsies were compared, and a complication analysis was conducted. RESULTS: A total of 50 patients were involved. Four cryobiopsies were taken from 49 patients, and a single biopsy was taken from one case. The sensitivities of one, two, three and four biopsies were 82, 93.9, 93.9 and 95.9 %, respectively. The difference in performance of one and two biopsies was significant (p = 0.031), but the third and fourth biopsies were found to be unnecessary (p = 1.0 for second versus third and p = 1.0 for second versus fourth). Bleeding risk increased when >=3 cryobiopsies were taken (Odds Ratio 2.758). CONCLUSIONS: When the diagnostic benefits and complication rates were considered, two cryobiopsies were found to be optimal for endobronchial tumors. In patients with non-diagnostic conventional bronchoscopy, endobronchial tumors may be diagnosed by cryobiopsy. PMID- 27412128 TI - Improved multilocus sequence typing of Burkholderia pseudomallei and closely related species. AB - The Burkholderiapseudomallei multilocus sequence typing (MLST) database (http://pubmlst.org/bpseudomallei/) contains the largest global sequence repository for B. pseudomallei and its closest genetic relatives. Using conventional MLST and in silico MLST data derived from publicly available whole genome sequences, we first defined the phylogenetic relatedness of B. pseudomallei and its nearest neighbours. Based on this analysis, we propose that the recently described B. pseudomallei complex (Bpc) should be expanded to encompass B. pseudomallei, Burkholderiahumptydooensis (proposed), Burkholderiamallei, Burkholderiaoklahomensis, Burkholderiathailandensis and three unassigned Burkholderia Clades A, B and C (represented by type strains BDU 5, BDU 8 and MSMB0265, respectively). Of note, the MLST narK locus is present in all Bpc species but is missing in all other Burkholderia spp., including all Burkholderiacepacia complex species, with the exception of most Burkholderiaubonensis strains, which contain narK but encode genetically distinct sequences. The presence of narK is thus indicative of a Bpc strain. Next, we revisited in silico the performance of the existing MLST primers, which prompted redesign of primers targeting the gmhD, lepA, lipA, narK and ndh loci to encompass genetic diversity among Bpc strains and to address amplification/sequencing issues. We show in silico and in vitro that the redesigned primers yield good-quality amplification and sequencing results for the gmhD, lepA, lipA, narK and ndh loci in Bpc species. These primers provide an alternative for amplification and sequencing of MLST loci in Bpc species in cases when poor-quality amplification or sequencing data are obtained using the original MLST primers. PMID- 27412130 TI - The thermoelectrochemistry of lithium-glyme solvate ionic liquids: towards waste heat harvesting. AB - Thermoelectrochemistry offers a simple, scalable technique for direct conversion of waste heat into useful electricity. Here the thermoelectrochemical properties of lithium-glyme solvate ionic liquids, as well as their dilute electrolyte analogues, have been investigated using mixtures of tetraglyme (G4, tetraethylene glycol dimethyl ether) and lithium bis(trifluoromethylsulfonyl)imide (Li[NTf2]). The thermoelectrochemical process is entropically-driven by release of the glyme from the lithium-glyme complex cation, due to electrodeposition of lithium metal at the hotter lithium electrode with concomitant electrodissolution at the cooler lithium electrode. The optimum ratio for thermochemical electricity generation is not the solvate ionic liquid (equimolar mixture of Li[NTf2] and glyme), but rather one Li[NTf2] to four G4, due to the mixtures relatively high ionic conductivity and good apparent Seebeck coefficient (+1.4 mV K(-1)). Determination of the lithium-glyme mixture thermal conductivity enabled full assessment of the Figure of Merit (ZT), and the efficiency relative to the Carnot efficiency to be determined. As the lithium electrodeposits are porous, alternating the temperature gradient results in a system that actually improves with repeated use. PMID- 27412129 TI - New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives. AB - Light is known to excite photosensitizers (PS) to produce cytotoxic reactive oxygen species (ROS) in the presence of oxygen. This modality is attractive for designing control measures against animal diseases and pests. Many PS have a proven safety record. Also, the ROS cytotoxicity selects no resistant mutants, unlike other drugs and pesticides. Photodynamic therapy (PDT) refers to the use of PS as light activable tumoricides, microbicides and pesticides in medicine and agriculture.Here we describe "photodynamic vaccination" (PDV) that uses PDT inactivation of parasites, i.e. Leishmania as whole-cell vaccines against leishmaniasis, and as a universal carrier to deliver transgenic add-on vaccines against other infectious and malignant diseases. The efficacy of Leishmania for vaccine delivery makes use of their inherent attributes to parasitize antigen (vaccine)-presenting cells. Inactivation of Leishmania by PDT provides safety for their use. This is accomplished in two different ways: (i) chemical engineering of PS to enhance their uptake, e.g. Si-phthalocyanines; and (ii) transgenic approach to render Leishmania inducible for porphyrinogenesis. Three different schemes of Leishmania-based PDV are presented diagrammatically to depict the cellular events resulting in cell-mediated immunity, as seen experimentally against leishmaniasis and Leishmania-delivered antigen in vitro and in vivo. Safety versus efficacy evaluations are under way for PDT-inactivated Leishmania, including those further processed to facilitate their storage and transport. Leishmania transfected to express cancer and viral vaccine candidates are being prepared accordingly for experimental trials.We have begun to examine PS-mediated photodynamic insecticides (PDI). Mosquito cells take up rose bengal/cyanosine, rendering them light-sensitive to undergo disintegration in vitro, thereby providing a cellular basis for the larvicidal activity seen by the same treatments. Ineffectiveness of phthalocyanines and porphyrins for PDI underscores its requirement for different PS. Differential uptake of PS by insect versus other cells to account for this difference is under study.The ongoing work is patterned after the one-world approach by enlisting the participation of experts in medicinal chemistry, cell/molecular biology, immunology, parasitology, entomology, cancer research, tropical medicine and veterinary medicine. The availability of multidisciplinary expertise is indispensable for implementation of the necessary studies to move the project toward product development. PMID- 27412131 TI - Oral anti-pseudomonal antibiotics for cystic fibrosis. AB - BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review. OBJECTIVES: To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information. MAIN RESULTS: We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the included trials reported significantly better lung function when treating a pulmonary exacerbation with ciprofloxacin when compared with intravenous treatment; however, our analysis did not confirm this finding. We found no evidence of difference between oral anti-pseudomonal antibiotics and other treatments regarding adverse events or development of antibiotic resistance, but trials were not adequately powered to detect this. None of the studies had a low risk of bias from blinding which may have an impact particularly on subjective outcomes such as quality of life. The risk of bias for other criteria could not be clearly stated across the studies. AUTHORS' CONCLUSIONS: We found no conclusive evidence that an oral anti-pseudomonal antibiotic regimen is more or less effective than an alternative treatment for either pulmonary exacerbations or long-term treatment of chronic infection with P. aeruginosa. Until results of adequately-powered future trials are available, treatment needs to be selected on a pragmatic basis, based upon any available non randomised evidence, the clinical circumstances of the individual, the known effectiveness of drugs against local strains and upon individual preference. PMID- 27412132 TI - Two Conformers of N,N-Diethylpropionamide As Observed by Microwave Spectroscopy and Quantum Chemistry. AB - The microwave spectra of two conformers of N,N-diethylpropionamide were recorded using a molecular beam Fourier transform microwave spectrometer operating in the frequency range 2-26.5 GHz. Hyperfine splittings arising from the (14)N quadrupole coupling effect were observed and analyzed. Fits using a rigid rotor model with centrifugal distortion correction and first-order perturbation approach for the quadrupole coupling yielded highly accurate molecular parameters and standard deviations within the measurement accuracy for both conformers. Complementary quantum chemical calculations were carried out for a conformational analysis, theoretical values of the spectroscopic constants, and the (14)N nuclear quadrupole coupling constants. PMID- 27412133 TI - Analysis of the body composition of Paralympic athletes: Comparison of two methods. AB - Body composition is a physiological variable associated with physical activity and, in some cases, is related to athletic performance. Our objectives were to describe the body composition of participants in three distinct Paralympic sports and to compare the values of body density and estimated body fat obtained from the Paralympic athletes on the National Team by air-displacement plethysmography (ADP) and by the anthropometric method (skinfolds (SFs)). The sample consisted of 70 volunteers of both genders. The body composition of the volunteers was evaluated using the ADP in a Bod Pod((r)) and seven SFs. There were no significant differences between the values obtained by ADP and SF for body fat percentage (p = .58) and body density (p = .49). Analysis by Bland-Altman plots showed mean differences of 0.56 +/- 4.94 (-9.12-10.23) and -0.0017 +/- 0.0113 ( 0.024-0.020) for body fat percentage and body density, respectively. In conclusion, body composition analyses of Paralympic athletes by the ADP and SF methods show similar results, and ADP should be used as the first option when available. When the use of ADP is not possible, estimating body density and fat percentage by SF is a viable alternative for Paralympic athletes when future comparisons will use the same analysis method. PMID- 27412134 TI - Incontinentia Pigmenti with Persistent Hypercalcemia: Case Report. AB - Incontinentia pigmenti (IP) is an X-linked dominant disorder that in most cases is considered lethal in males. IP affects the skin, hair, teeth, nails, eyes, and central nervous system. We report a case of persistent hypercalcemia (10.6-11.3 mg/dL) in a 19-month-old Caucasian boy with clinical IP. The proposed mechanism for his hypercalcemia is discussed. PMID- 27412135 TI - A critical evaluation of the effectiveness of interventions for improving the well-being of caregivers of children with cerebral palsy: a systematic review protocol. AB - BACKGROUND: Over the years, family-centered care has evolved as the "gold standard" model for the provision of healthcare services. With the advent of family-centered approach to care comes the inherent need to provide support services to caregivers in addition to meeting the functional needs of children with physical disabilities such as cerebral palsy (CP). Provision of care for a child with CP is invariably associated with poor health outcomes in caregivers. As such, there has been a surge in the development and implementation of interventions for improving the health and well-being of these caregivers. However, there is a paucity of the collective, empirical evidence of the efficacy of these interventions. Therefore, the broad objective of this review is to systematically review the literature on the effectiveness of interventions designed to improve caregivers' well-being. METHODS/DESIGN: This is a systematic review for the evaluation of the effectiveness of interventions designed to improve caregivers' well-being. Two independent, blinded, reviewers will search articles on PubMed, Scopus, Web of Science, CINAHL, Psych Info, and Africa-Wide Information using a predefined criterion. Thereafter, three independent reviewers will screen the retrieved articles. The methodological quality of studies meeting the selection criterion will be evaluated using the Briggs Institute checklists. Afterwards, two independent researchers will then apply a preset data-extraction form to collect data. We will perform a narrative data analysis of the final sample of studies included for the review. DISCUSSION: The proposed systematic review will provide the empirical evidence of the efficacy of interventions for improving the well-being of caregivers of children with physical disabilities. This is important given the great need for evidenced-based care and the greater need to improve the health and well-being of caregivers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033975. PMID- 27412136 TI - Nonstenotic carotid plaques: Stroke causation or guilt by association? PMID- 27412138 TI - Rydel-Seiffer fork revisited: Beyond a simple case of black and white. PMID- 27412137 TI - Gray matter maturation and cognition in children with different APOE epsilon genotypes. AB - OBJECTIVE: The aims of the current study were to determine whether children with the 6 different APOE epsilon genotypes show differences in gray matter maturation, particularly for those with epsilon4 and epsilon2 alleles, which are associated with poorer outcomes in many neurologic disorders. METHODS: A total of 1,187 healthy children (aged 3-20 years, 52.1% boys, 47.9% girls) with acceptable data from the cross-sectional Pediatric Imaging Neurocognition and Genetics Study were evaluated for the effects of 6 APOE epsilon genotypes on macroscopic and microscopic cortical and subcortical gray matter structures (measured with 3 tesla MRI and FreeSurfer for automated morphometry) and on cognition (NIH Toolbox). RESULTS: Among APOE epsilon4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in epsilon2epsilon4 children, the lowest hippocampal fractional anisotropy in younger epsilon4epsilon4 children, the largest medial orbitofrontal cortical areas in epsilon3epsilon4 children, and age-dependent thinning of the entorhinal cortex in epsilon4epsilon4 children. Younger epsilon4epsilon4 children had the lowest scores on executive function and working memory, while younger epsilon2epsilon4 children performed worse on attention tasks. Larger parietal gyri in the younger epsilon2epsilon4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger epsilon4epsilon4 children, predicted poorer performance on attention or working memory. CONCLUSIONS: Our findings validated and extended prior smaller studies that showed altered brain development in APOE epsilon4-carrier children. The epsilon4epsilon4 and epsilon2epsilon4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE epsilon polymorphisms in young children may provide the earliest indicators for individuals who might benefit from early interventions or preventive measures for future brain injuries and dementia. PMID- 27412139 TI - Imaging and rare APOE alleles: Alzheimer disease as a developmental disorder. PMID- 27412140 TI - Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease). AB - OBJECTIVE: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis as a route to further gene discovery. METHODS: Through establishment of an international consortium we pooled 47 unsolved cases regarded by referring centers as ANCL. Clinical and neuropathologic experts within the Consortium established diagnostic criteria for ANCL based on the literature to assess each case. A panel of 3 neuropathologists independently reviewed source pathologic data. Cases were given a final clinicopathologic classification of definite ANCL, probable ANCL, possible ANCL, or not ANCL. RESULTS: Of the 47 cases, only 16 fulfilled the Consortium's criteria of ANCL (5 definite, 2 probable, 9 possible). Definitive alternate diagnoses were made in 10, including Huntington disease, early-onset Alzheimer disease, Niemann-Pick disease, neuroserpinopathy, prion disease, and neurodegeneration with brain iron accumulation. Six cases had features suggesting an alternate diagnosis, but no specific condition was identified; in 15, the data were inadequate for classification. Misinterpretation of normal lipofuscin as abnormal storage material was the commonest cause of misdiagnosis. CONCLUSIONS: Diagnosis of ANCL remains challenging; expert pathologic analysis and recent molecular genetic advances revealed misdiagnoses in >1/3 of cases. We now have a refined group of cases that will facilitate identification of new causative genes. PMID- 27412143 TI - Comment: Noninvasive vagus DBS-Preliminary study encouraging for chronic migraine. PMID- 27412141 TI - Racial-ethnic disparities in acute blood pressure after intracerebral hemorrhage. AB - OBJECTIVE: To assess race-ethnic differences in acute blood pressure (BP) following intracerebral hemorrhage (ICH) and the contribution to disparities in ICH outcome. METHODS: BPs in the field (emergency medical services [EMS]), emergency department (ED), and at 24 hours were compared and adjusted for group differences between non-Hispanic black (black), non-Hispanic white (white), and Hispanic participants in the Ethnic Racial Variations of Intracerebral Hemorrhage case-control study. Outcome was obtained by modified Rankin Scale (mRS) score at 3 months. We analyzed race-ethnic differences in good outcome (mRS <= 2) and mortality after adjusting for baseline differences and included BP recordings in this model. RESULTS: Of 2,069 ICH cases enrolled, 30% were white, 37% black, and 33% Hispanic. Black and Hispanic patients had higher EMS and ED systolic and diastolic BPs compared with white patients (p = 0.0001). Although attenuated, at 24 hours after admission, black patients had higher systolic and diastolic BPs. After adjusting for baseline differences, significant race/ethnic differences persisted for EMS systolic, ED systolic and diastolic, and 24-hours diastolic BP. Only ED systolic and diastolic BP was associated with poor functional outcome, and no BP predicted mortality. We found no race-ethnic differences in 3-month functional outcome or mortality after adjusting for group differences, including acute BPs. CONCLUSIONS: Although black and Hispanic patients had higher BPs than white patients at presentation, we did not find race-ethnic disparities in 3 month functional outcome or mortality. ED systolic and diastolic BP was associated with poor functional outcome, but not mortality, in this race ethnically diverse population. PMID- 27412142 TI - Diffusion-weighted MRI abnormalities antedate the onset of sporadic Creutzfeldt Jakob disease. PMID- 27412144 TI - Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke. AB - OBJECTIVE: To determine whether large (>=3 mm thick) but nonstenotic (<50%) carotid artery atherosclerotic plaque predominantly occurs ipsilateral rather than contralateral to cryptogenic stroke. METHODS: This was a cross-sectional observational study. Using a stroke registry, we identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS). Using CT angiography, we measured carotid plaque size (thickness, mm) and carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial method) for each patient. We dichotomized plaque size at several predefined thresholds and calculated the frequency of plaque size above each threshold ipsilateral vs contralateral to stroke. RESULTS: We included 85 patients with ESUS. Plaque with thickness >=5 mm was present ipsilateral to stroke in 11% of patients, and contralateral in 1% (9/85 vs 1/85; p = 0.008). Plaque with thickness >=4 mm was present ipsilateral to stroke in 19% of patients, and contralateral in 5% (16/85 vs 4/85; p = 0.002). Plaque with thickness >=3 mm was present ipsilateral to stroke in 35% of patients, and contralateral in 15% (30/85 vs 13/85; p = 0.001). There was no difference in percentage stenosis ipsilateral vs contralateral to stroke (p = 0.98), and weak correlation between plaque size and stenosis (R(2) = 0.26, p < 0.001). CONCLUSIONS: Large but nonstenotic carotid artery plaque is considerably more common ipsilateral than contralateral to cryptogenic stroke, suggesting that nonstenotic plaque is an underrecognized cause of stroke. We measured plaque size using CT angiography, a method that could be easily implemented in clinical practice. PMID- 27412145 TI - Role of emergent chest radiography in evaluation of hyperacute stroke. AB - OBJECTIVE: To use data from a large multicenter trial to assess the role and significance of chest radiograph (CXR) in the initial evaluation of acute stroke. METHODS: Predefined clinical characteristics of patients who had recorded data on CXR examination during the initial evaluation were collected. We compared features of patients who had a CXR done before IV thrombolytics with those who did not. Rates of adverse cardiopulmonary events, intubation, and in-hospital mortality were also compared. Logistic regression analysis was performed to evaluate for the association of CXR performance with door-to-needle time >=60 minutes. RESULTS: In a cohort of 615 patients, 243 had CXR done before IV thrombolytics. Patients with CXR before treatment had significantly higher admission neurologic deficit, initial respiratory rates, and door-to-needle time than those with CXR after treatment. The rates of cardiopulmonary adverse events in the first 24 hours of admission, endotracheal intubation in the first 7 hours, and in-hospital mortality were not different between the 2 groups. Patients with CXR done before treatment had longer mean door-to-needle times than those without pretreatment radiography (75.8 vs 58.3 minutes, p = 0.0001). Performance of CXR was independently associated with door-to-needle time >=60 minutes (odds ratio 2.78, 95% confidence interval 1.97-3.92; p = 0.00001). CONCLUSIONS: Performance of CXR prior to IV thrombolytics prolongs door-to-needle time in acute ischemic stroke patients. CXR before treatment should be reserved for situations wherein acute cardiopulmonary conditions would otherwise preclude the administration of IV thrombolytics or substantially influence management. PMID- 27412147 TI - Higher risks when working unusual times? A cross-validation of the effects on safety, health, and work-life balance. AB - PURPOSE: Replication and cross-validation of results on health and safety risks of work at unusual times. METHODS: Data from two independent surveys (European Working Conditions Surveys 2005 and 2010; EU 2005: n = 23,934 and EU 2010: n = 35,187) were used to examine the relative risks of working at unusual times (evenings, Saturdays, and Sundays) on work-life balance, work-related health complaints, and occupational accidents using logistic regression while controlling for potential confounders such as demographics, work load, and shift work. RESULTS: For the EU 2005 survey, evening work was significantly associated with an increased risk of poor work-life balance (OR 1.69) and work-related health complaints (OR 1.14), Saturday work with poor work-life balance (OR 1.49) and occupational accidents (OR 1.34), and Sunday work with poor work-life balance (OR 1.15) and work-related health complaints (OR 1.17). For EU 2010, evening work was associated with poor work-life balance (OR 1.51) and work-related health complaints (OR 1.12), Saturday work with poor work-life balance (OR 1.60) and occupational accidents (OR 1.19) but a decrease in risk for work-related health complaints (OR 0.86) and Sunday work with work-related health complaints (OR 1.13). Risk estimates in both samples yielded largely similar results with comparable ORs and overlapping confidence intervals. CONCLUSIONS: Work at unusual times constitutes a considerable risk to social participation and health and showed structurally consistent effects over time and across samples. PMID- 27412146 TI - Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. AB - OBJECTIVE: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks. METHODS: In this first prospective, multicenter, double-blind, sham controlled pilot study of nVNS in CM prophylaxis, adults with CM (>=15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use. RESULTS: Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Delta = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01). CONCLUSIONS: Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed. CLINICALTRIALSGOV IDENTIFIER: NCT01667250. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS. PMID- 27412148 TI - High dose subcutaneous immunoglobulin for idiopathic inflammatory myopathies and dysimmune peripheral chronic neuropathies treatment: observational study of quality of life and tolerance. AB - BACKGROUND: In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. OBJECTIVE: To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. METHODS: This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. RESULTS: Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. CONCLUSION: In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg. PMID- 27412150 TI - Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers. AB - Extensive efforts have been devoted to develop new substrates for culture and differentiation of human induced pluripotent stem cells (hiPSCs) toward cardiac cell-based assays. A more exciting prospect is the construction of cardiac tissue for robust drug screening and cardiac tissue repairing. Here, we developed a patch method by electrospinning and crosslinking of monolayer gelatin nanofibers on a honeycomb frame made of poly(ethylene glycol) diacrylate (PEGDA). The monolayer of the nanofibrous structure can support cells with minimal exogenous contact and a maximal efficiency of cell-medium exchange whereas a single hiPSC colony can be uniformly formed in each of the honeycomb compartments. By modulating the treatment time of the ROCK inhibitor Y-27632, the shape of the hiPSC colony could be controlled from a flat layer to a hemisphere. Afterwards, the induction and differentiation of hiPSCs were achieved on the same patch, leading to a uniform cardiac layer with homogeneous contraction. This cardiac layer could then be used for extracellular recording with a commercial multi electrode array, showing representative field potential waveforms of matured cardiac tissues with appropriate drug responses. PMID- 27412151 TI - Development of a multispectral light-scatter sensor for bacterial colonies. AB - We report a multispectral elastic-light-scatter instrument that can simultaneously detect three-wavelength scatter patterns and associated optical densities from individual bacterial colonies, overcoming the limits of the single wavelength predecessor. Absorption measurements on liquid bacterial samples revealed that the spectroscopic information can indeed contribute to sample differentiability. New optical components, including a pellicle beam splitter and an optical cage system, were utilized for robust acquisition of multispectral images. Four different genera and seven shiga toxin producing E. coli serovars were analyzed; the acquired images showed differences in scattering characteristics among the tested organisms. In addition, colony-based spectral optical-density information was also collected. The optical model, which was developed using diffraction theory, correctly predicted wavelength-related differences in scatter patterns, and was matched with the experimental results. Scatter-pattern classification was performed using pseudo-Zernike (GPZ) polynomials/moments by combining the features collected at all three wavelengths and selecting the best features via a random-forest method. The data demonstrate that the selected features provide better classification rates than the same number of features from any single wavelength. Three wavelength-merged scatter pattern from E. coli. PMID- 27412149 TI - A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals. AB - BACKGROUND: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. METHODS: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. RESULTS: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. CONCLUSIONS: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible. PMID- 27412152 TI - Presentation to publication: proportion of abstracts published for ESPR, SPR and IPR. AB - BACKGROUND: Advancement of knowledge requires presentation and publication of high-quality scientific research. Studies submitted for presentation undergo initial peer review before acceptance and the rate of subsequent publication may be taken as an indicator of access to publication for pediatric radiology studies. OBJECTIVES: Evaluate the proportion of abstracts also published in journals for pediatric radiology conferences and identify factors associated with publication success. MATERIALS AND METHODS: All Medline articles that originated from oral presentations at the European Society for Paediatric Radiology (ESPR), the Society for Pediatric Radiology (SPR) or the International Pediatric Radiology (IPR) conferences between 2010 - 2012 were evaluated. Descriptive statistics to evaluate published and unpublished groups were calculated overall and split by characteristics of the abstracts such as number of authors. RESULTS: Overall number of abstracts published was 300/715 (41.9%), with most articles published in radiology specific journals (181/300; 60.3%), with median impact factor 2.31 (interquartile range [IQR]: 1.65-3.14, range: 0-18.03). Those published after the conference (262/300, 87.6%) had a median time to publication of 18 months and for those published before, the median time was -11 months. Median sample size in published articles was 52 (IQR: 33-105, range: 1-6,351). CONCLUSION: Of pediatric radiology oral abstracts, 41.9% achieve publication after a period of at least 3 years from presentation. Studies originating from certain countries and on certain subspecialty topics were more likely to get published. PMID- 27412153 TI - Factors associated with maternal mortality at advanced maternal age: a population based case-control study. AB - OBJECTIVE: This study aimed to examine the factors associated with maternal mortality among women aged >=35 years. DESIGN: Unmatched population based case control study. SETTING: United Kingdom. POPULATION: Between 2009 and 2012, 105 cases of maternal deaths aged >=35 years were extracted from the surveillance database of the MBRRACE-UK confidential enquiries into maternal deaths in the UK. In addition, 766 controls aged >=35 years were identified from the UK Obstetric Surveillance System (2005-2012). METHODS: Risk factors known to be associated with maternal mortality and morbidity and for which data were available were examined for their association with maternal mortality among women >=35 years using logistic regression analysis. MAIN OUTCOME MEASURES: Odds ratios and 95% confidence intervals associated with maternal death. RESULTS: Five factors were found to be significantly associated with increased odds of death among women aged >=35 years: smoking during pregnancy (adjusted odds ratio (aOR) 2.06, 95% CI 1.13-3.75), inadequate use of antenatal care (aOR 23.62, 95% CI 8.79-63.45), medical co-morbidities (aOR 5.92, 95% CI 3.56-9.86) and previous pregnancy problems (aOR 2.06, 95% CI 1.23-3.45). The odds associated with death increased by 12% per year increase in age (aOR 1.12, 95% CI 1.02-1.22). CONCLUSION: Age was associated with maternal mortality even after adjusting for other known risk factors. Importantly, this study showed an association between maternal mortality and smoking among women aged 35 years or older. It emphasises the importance of public health action to reduce smoking levels and address trends in rising maternal age. TWEETABLE ABSTRACT: Smoking is a risk factor for maternal death for those aged over 35 years. PMID- 27412154 TI - Do HLA class II genes protect against pulmonary tuberculosis? A systematic review and meta-analysis. AB - Pulmonary tuberculosis (PTB) develops by a complex combination of environmental, immunological and socioeconomic factors and genetic susceptibility. The human leukocyte antigen (HLA) is the most polymorphic biological system and plays an essential role in the immune response against PTB. The aim of this study was to carry out a systematic review and meta-analysis evaluating the relationship between HLA-DRB1, HLA-DQB1 and HLA-DQA1 gene polymorphisms as possible risk or protective factors for PTB. A systematic search of the PubMed and Scopus databases was conducted following the guidelines described in the PRISMA statement. Fifty-six alleles were included in the meta-analysis. In the total pooled results, HLA-DRB1*08:03 (OR 1.95, CI 1.29-2.96), HLA-DQB1*06:01 (OR 1.78, CI 1.39-2.28), HLA-DQB1*06:09 (OR 2.27, 95 % CI 1.04-4.96) and HLA-DQA1*01:01 (OR 2.12, CI 1.11-4.03) genes were related to higher susceptibility to PTB. Conversely, the presence of the genes HLA-DRB1*07:01 (OR 0.74, CI 0.56-0.97), HLA DQB1*03:01 (OR 0.77, CI 0.61-0.97), HLA-DQB1*04:02 (OR 0.57, CI 0.39-0.83), HLA DQA1*04:01 (OR 0.50, CI 0.26-0.95) and HLA-DQA1*05:01 (OR 0.66, CI 0.48-0.92) demonstrated protection against PTB. In an analysis by ethnic subgroups, we found more genetic associations in Caucasians than in Asians. These findings suggest that HLAs may be used as markers for acquisition and development of PTB. To strengthen PTB susceptibility/resistance, we recommend further multicentric studies in different geographic regions, with certainty of controls' exposure to M. tuberculosis by use of marker of latent or active PTB, with analysis stratified by ethnic groups, with descriptions of specific alleles and carrying out immunological functionality tests. PMID- 27412155 TI - Performance and diversity of polyvinyl alcohol-degrading bacteria under aerobic and anaerobic conditions. AB - OBJECTIVES: To compare the degradation performance and biodiversity of a polyvinyl alcohol-degrading microbial community under aerobic and anaerobic conditions. RESULTS: An anaerobic-aerobic bioreactor was operated to degrade polyvinyl alcohol (PVA) in simulated wastewater. The degradation performance of the bioreactor during sludge cultivation and the microbial communities in each reactor were compared. Both anaerobic and aerobic bioreactors demonstrated high chemical oxygen demand removal efficiencies of 87.5 and 83.6 %, respectively. Results of 16S rDNA sequencing indicated that Proteobacteria dominated in both reactors and that the microbial community structures varied significantly under different operating conditions. Both reactors obviously differed in bacterial diversity from the phyla Planctomycetes, Chlamydiae, Bacteroidetes, and Chloroflexi. Betaproteobacteria and Alphaproteobacteria dominated, respectively, in the anaerobic and aerobic reactors. CONCLUSIONS: The anaerobic-aerobic system is suitable for PVA wastewater treatment, and the microbial genetic analysis may serve as a reference for PVA biodegradation. PMID- 27412156 TI - Computer Simulator of Glycine Receptor Activity: A New Window into a Virtual World. AB - Our study reports computer software that simulates the work of a single glycine receptor (GlyR). GlyRs have been found in various types of tissues, but their most important role seems to be in neurons, where they hyperpolarise membranes by opening chloride transmembrane channels. The software is based on a combination of two blocks. One block describes the Brownian dynamics of charged particle motion in a dielectric medium, and the other block determines the probability and timing of receptor activation. Using this software, the voltage-current dependencies and time curves of the transmembrane current were obtained. The mean value of the simulated anion current (4.5 +/- 0.3 pA) is in good agreement with measured values under identical conditions ([Formula: see text] pA). It was shown that there is a condition under which the GlyR anion channel remains active despite a negligible chloride gradient. Virtual experiments allow evaluation of the value of half maximal effective concentration (EC[Formula: see text]) of the GlyR ([Formula: see text] [Formula: see text]M) and confirm that this receptor activates according to a mechanism involving three ligand binding sites. The advantage of the model is the ability to adjust parameters to the precise demands of experimental researchers. Moreover, the introduced algorithm has low computational power demands; therefore, it can be used as a research tool for assistance with structural experiments and applied aspects of neurophysiology. PMID- 27412157 TI - A Turing-Hopf Bifurcation Scenario for Pattern Formation on Growing Domains. AB - In this paper, we study the emergence of different patterns that are formed on both static and growing domains and their bifurcation structure. One of these is the so-called Turing-Hopf morphogenetic mechanism. The reactive part we consider is of FitzHugh-Nagumo type. The analysis was carried out on a flat square by considering both fixed and growing domain. In both scenarios, sufficient conditions on the parameter values are given for the formation of specific space time structures or patterns. A series of numerical solutions of the corresponding initial and boundary value problems are obtained, and a comparison between the resulting patterns on the fixed domain and those arising when the domain grows is established. We emphasize the role of growth of the domain in the selection of patterns. The paper ends by listing some open problems in this area. PMID- 27412158 TI - Stability and Bionomic Analysis of Fuzzy Prey-Predator Harvesting Model in Presence of Toxicity: A Dynamic Approach. AB - This paper deals with a prey-predator model in which both the species are infected by some toxicants which are released by some other species or source with fuzzy biological parameters. The application of fuzzy differential equation in the modeling of prey-predator populations with the effect of toxicants is presented. The dynamical behavior and harvesting of the fuzzy exploited system are studied by using the utility function method. Sufficient conditions for the local stability of the positive equilibrium are obtained by analyzing the characteristic equation. Furthermore, the possibility of the existence of bionomic equilibrium is studied under imprecise biological parameters. The study of the presence of toxic substance and harvesting in the modeling system can have significant impact on the existence of both the species, which is in line with reality. Numerical simulation results are presented to validate the theoretical analysis. PMID- 27412159 TI - Health survey of adults with hereditary spastic paraparesis compared to population study controls. AB - BACKGROUND: Hereditary spastic paraparesis (HSP) is a rare neurodegenerative condition characterized by slowly progressive spastic weakness of the lower limbs and urinary sphincter dysfunction. Complex HSP involves additional neurologic symptoms and signs like ataxia, extra pyramidal signs, polyneuropathy, and cognitive decline. Little is known about the disease burden for adults with HSP beyond the described core symptoms. METHODS: A cross-sectional survey of 108 adults aged 30 years and older (Mage = 57.7 years, SD = 11.5, range 30 to 81; 54.2 % females) recruited from a national center of expertise for rare disorders and a patient advocacy organization in Norway. Self-report data from the HSP sample was compared to self-report data from a large Norwegian population study, HUNT3 (N = 46,293), covering health-related variables such as overall life satisfaction, mental wellbeing, memory function, perceived pain, and co-morbid diseases. In addition, the HSP sample reported specific items developed for this study in co-operation with the patient advocacy organization. RESULTS: The HSP sample more frequently lived alone. Overall, the HSP sample reported lower life satisfaction, lower mental wellbeing and lower social support, as well as poorer memory and sleep, compared to controls. Furthermore, the HSP sample more frequently reported musculoskeletal pain, constipation, and urinary incontinence compared to controls. There was no difference between samples in frequency of physical activity and alcohol and tobacco use. Men with HSP reported higher impact of HSP, lower life satisfaction, and less ability to perform activities of daily living compared to women with HSP. CONCLUSIONS: Adults with HSP experience disease burden on a larger number of areas than previously documented, and men with HSP may represent a particularly vulnerable group. PMID- 27412161 TI - Diagnosis of takotsubo cardiomyopathy is increasing over time in patients presenting as ST-elevation myocardial infarction. AB - BACKGROUND: Takotsubo cardiomyopathy often presents with the clinical signs of ST elevation myocardial infarction (STEMI). The increase in scientific publications addressing this relatively rare condition may result in higher awareness and diagnosis of takotsubo cardiomyopathy. AIM: To assess the observed prevalence per year of takotsubo cardiomyopathy in a large registry of patients with STEMI, during a 12-year inclusion period. METHOD: All patients presenting with STEMI at a large regional cardiology clinic were entered into a database (n = 8,413, mean age 63 +/- 13 years). Takotsubo cardiomyopathy was diagnosed in 42 patients (0.5 %). Years of evaluation were defined as 'early years' (January 2002 to December 2007; n = 4350) and 'later years' (January 2008 to December 2013). Multivariable analyses were performed to adjust for differences in demographical and clinical variables. RESULTS: In later years, the age of STEMI patients was slightly higher (64 +/- 13 vs. 63 +/- 13 years, p < 0.001), with more patients with clinical symptoms of shock (10 vs. 7 %, p < 0.001) or a history of percutaneous coronary intervention or hypertension (10 vs. 8 %, p = 0.001 and 37 vs. 34 %, p < 0.001). Smoking and a positive family history were less often observed during later years (39 vs. 46 %, p < 0.001 and 37 vs. 42 % p < 0.001). Patients with takotsubo cardiomyopathy were more often female (81 vs. 27 %, p = 0.001). Takotsubo cardiomyopathy was more often diagnosed in the later period (0.7 vs. 0.3 %, OR 2.4, 95 % CI 1.2-4.6, p = 0.009). The higher prevalence of takotsubo cardiomyopathy in recent years remained significant after adjustment for differences in patient characteristics (OR 2.1, 95 % CI 1.1-4.3). CONCLUSION: Takotsubo cardiomyopathy is currently more often diagnosed in patients with STEMI compared with in earlier years. This is probably due to the increased scientific and clinical awareness among doctors, but the prevalence is still low. PMID- 27412160 TI - The experimental design of postmortem studies: the effect size and statistical power. AB - PURPOSE: The aim is of this study was to show the poor statistical power of postmortem studies. Further, this study aimed to find an estimate of the effect size for postmortem studies in order to show the importance of this parameter. This can be an aid in performing power analysis to determine a minimal sample size. METHODS: GPower was used to perform calculations on sample size, effect size, and statistical power. The minimal significance (alpha) and statistical power (1 - beta) were set at 0.05 and 0.80 respectively. Calculations were performed for two groups (Student's t-distribution) and multiple groups (one-way ANOVA; F-distribution). RESULTS: In this study, an average effect size of 0.46 was found (n = 22; SD = 0.30). Using this value to calculate the statistical power of another group of postmortem studies (n = 5) revealed that the average statistical power of these studies was poor (1 - beta < 0.80). CONCLUSION: The probability of a type-II error in postmortem studies is considerable. In order to enhance statistical power of postmortem studies, power analysis should be performed in which the effect size found in this study can be used as a guideline. PMID- 27412162 TI - Percutaneous tricuspid valve repair using MitraClip(r) for the treatment of severe tricuspid valve regurgitation in a patient with congenitally corrected transposition of the great arteries. PMID- 27412164 TI - [Not Available]. PMID- 27412163 TI - Poor survival in stage IIB/C (T4N0) compared to stage IIIA (T1-2 N1, T1N2a) colon cancer persists even after adjusting for adequate lymph nodes retrieved and receipt of adjuvant chemotherapy. AB - BACKGROUND: A survival paradox between Stage IIB/C and Stage IIIA colon cancers exists. It is unclear how adequate lymph nodes dissection (LN) and post-surgery chemotherapy contribute to the survival paradox. We intended to assess the impact of these two factors on the survival paradox. RESULTS: We evaluated 34,999 patients diagnosed with stage IIIA or stage IIB/C colon cancer in 2003-2012 from the National Cancer Data Base. The 5-year overall survival (OS) was 73.5 % for stage IIIA and 51.1 % for stage IIB/C (P < 0.0001). The 5-year OS was 84.1 % for stage IIIA with post-surgery chemotherapy, 70.8 % for stage IIB/C with >= 12 LNs retrieved with chemotherapy, 53.9 % for stage IIB/C < 12 LNs with chemotherapy, 49.5 % for stage IIIA without chemotherapy, 43.7 % for stage IIB/C >= 12 LNs retrieved without chemotherapy, to 27.7 % for stage IIB/C < 12 LNs without chemotherapy. Even among stage IIB/C who had optimal treatment (>=12 LNs retrieved, received chemotherapy), OS remains lower than stage IIIA with chemotherapy. After adjusting LN dissection and chemotherapy in addition to the adjustment of other clinical factors, the survival paradox was reduced from HR = 1.76 (95 % CI: 1.68-1.85) to HR 1.51 (95 % CI: 1.44-1.59). CONCLUSIONS: LN dissection and post-surgery chemotherapy partially explained the survival paradox. More research is warranted to identify other factors that contribute to this paradox. Future iteration of TNM staging system should take this into consideration. PMID- 27412165 TI - [Not Available]. PMID- 27412167 TI - Thinking beside the box: Should we care about the non-coding strand of the 16S rRNA gene? AB - The 16S rRNA gene (16S rDNA) codes for RNA that plays a fundamental role during translation in the ribosome and is used extensively as a marker gene to establish relationships among bacteria. However, the complementary non-coding 16S rDNA (nc16S rDNA) has been ignored. An idea emerged in the course of analyzing bacterial 16S rDNA sequences in search for nucleotide composition and substitution patterns: Does the nc16S rDNA code? If so, what does it code for? More importantly: Does 16S rDNA evolution reflect its own evolution or the evolution of its counterpart nc16S rDNA? The objective of this minireview is to discuss these thoughts. nc strands often encode small RNAs (sRNAs), ancient components of gene regulation. nc16S rDNA sequences from different bacterial groups were used to search for possible matches in the Bacterial Small Regulatory RNA Database. Intriguingly, the sequence of one published sRNA obtained from Legionella pneumophila (GenBank: AE0173541) showed high non-random similarity with nc16S rDNA corresponding in part to the V5 region especially from Legionella and relatives. While the target(s) of this sRNA is unclear at the moment, its mere existence might open up a new chapter in the use of the 16S rDNA to study relationships among bacteria. PMID- 27412166 TI - Using nonparametric conditional approach to integrate quality into efficiency analysis: empirical evidence from cardiology departments. AB - Health care providers are under pressure to improve both efficiency and quality. The two objectives are not always mutually consistent, because achieving higher levels of quality may require additional resources. The aim of this study is to demonstrate how the nonparametric conditional approach can be used to integrate quality into the analysis of efficiency and to investigate the mechanisms through which quality enters the production process. Additionally, we explain how the conditional approach relates to other nonparametric methods that allow integrating quality into efficiency analysis and provide guidance on the selection of an appropriate methodology. We use data from 178 departments of interventional cardiology and consider three different measures of quality: patient satisfaction, standardized mortality ratio, and patient radiation exposure. Our results refute the existence of a clear trade-off between efficiency and quality. In fact, the impact of quality on the production process differs according to the utilized quality measure. Patient satisfaction does not affect the attainable frontier but does have an inverted U-shaped effect on the distribution of inefficiencies; mortality ratio negatively impacts the attainable frontier when the observed mortality more than doubles the predicted mortality; and patient radiation exposure is not associated with the production process. PMID- 27412168 TI - Mutations in NalC induce MexAB-OprM overexpression resulting in high level of aztreonam resistance in environmental isolates of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is an opportunistic pathogen with high resistance to a wide variety of antimicrobials. The multidrug resistance pump MexAB-OprM promotes the efflux of various antibiotics, mostly when mutations accumulate in the transcriptional regulators MexR, NalC and NalD, thereby causing MexAB-OprM overexpression. In this work, a characterization of 50 P. aeruginosa isolates obtained from Brazilian agricultural soils to determine the reasons of their resistance to aztreonam was done. The majority of the isolates showed higher aztreonam resistance than wild-type strain by MIC method. DNA sequence analysis of mexR, nalC and nalD genes from 13 of these isolates showed the amino acid substitution in NalC for all tested isolates, just one mutation was detected in MexR and none in NalD. Furthermore, an increase in the level of mexA expression by real-time RT-PCR analysis in eight isolates harboring mutations in NalC was found. Although there was not a relationship between MIC of aztreonam and the level of mexA expression, on the other hand, the results presented here suggest that novel mutations in NalC, including Arg97-Gly and Ala186-Thr, are related to MexAB-OprM overexpression causing aztreonam resistance in P. aeruginosa environmental isolates. PMID- 27412169 TI - American Society for Microbiology resources in support of an evidence-based approach to teaching microbiology. AB - Numerous national reports have addressed the need for changing how science courses in higher education are taught, so that students develop a deeper understanding of critical concepts and the analytical and cognitive skills needed to address future challenges. This review presents some evidence-based approaches to curriculum development and teaching. Results from discipline-based education research indicate that it is critically important for educators to formulate learning goals, provide frequent and authentic assessments and actively engage students in their learning. Professional societies can play a role in helping to put these changes into practice. To this end, the American Society for Microbiology has developed a number of educational programs and resources, which are described here to encourage the implementation of student-centered learning in microbiology education. PMID- 27412170 TI - Model depicting aspects of audit and feedback that impact physicians' acceptance of clinical performance feedback. AB - BACKGROUND: Audit and feedback (A&F) is a strategy that has been used in various disciplines for performance and quality improvement. There is limited research regarding medical professionals' acceptance of clinical-performance feedback and whether feedback impacts clinical practice. The objectives of our research were to (1) investigate aspects of A&F that impact physicians' acceptance of performance feedback; (2) determine actions physicians take when receiving feedback; and (3) determine if feedback impacts physicians' patient-management behavior. METHODS: In this qualitative study, we employed grounded theory methods to perform a secondary analysis of semi-structured interviews with 12 VA primary care physicians. We analyzed a subset of interview questions from the primary study, which aimed to determine how providers of high, low and moderately performing VA medical centers use performance feedback to maintain and improve quality of care, and determine perceived utility of performance feedback. RESULTS: Based on the themes emergent from our analysis and their observed relationships, we developed a model depicting aspects of the A&F process that impact feedback acceptance and physicians' patient-management behavior. The model is comprised of three core components - Reaction, Action and Impact - and depicts elements associated with feedback recipients' reaction to feedback, action taken when feedback is received, and physicians modifying their patient-management behavior. Feedback characteristics, the environment, external locus-of-control components, core values, emotion and the assessment process induce or deter reaction, action and impact. Feedback characteristics (content and timeliness), and the procedural justice of the assessment process (unjust penalties) impact feedback acceptance. External locus-of-control elements (financial incentives, competition), the environment (patient volume, time constraints) and emotion impact patient-management behavior. Receiving feedback generated intense emotion within physicians. The underlying source of the emotion was the assessment process, not the feedback. The emotional response impacted acceptance, impelled action or inaction, and impacted patient-management behavior. Emotion intensity was associated with type of action taken (defensive, proactive, retroactive). CONCLUSIONS: Feedback acceptance and impact have as much to do with the performance assessment process as it does the feedback. In order to enhance feedback acceptance and the impact of feedback, developers of clinical performance systems and feedback interventions should consider multiple design elements. PMID- 27412171 TI - Insulin-Like Growth Factor 2 - The Oncogene and its Accomplices. AB - The era of personalized medicine for cancer treatment has just begun opening up novel molecular targets improving cancer therapy. Members of the insulin-like growth factor 2 (IGF2) axis have been described to be altered and to have prognostic relevance in several different tumor identities. IGF2 belongs to the most complexly regulated growth factors known. As an imprinted gene it is controlled by epigenetic alterations. IGF2 mRNA binding proteins (IMPs/IGF2BPs) further regulate its translation. IGF2 activity is contained through IGF binding proteins (IGFBPs) and differential expression of the target receptors. The necessity of such a complex regulation implies pathophysiological effects of a deregulated expression of IGF2. This review attempts to summarize the different levels of IGF2 regulation, especially in the context of cancer. Members of the IGF2 axis are enlightened from the perspective of novel molecular targets for cancer therapy. Preclinical as well as experimental therapeutic interventions targeting IGF2 in cancer will be surveyed. PMID- 27412172 TI - Methyl gallate, a potent antioxidant inhibits mouse and human adipocyte differentiation and oxidative stress in adipocytes through impairment of mitotic clonal expansion. AB - Methyl gallate (MG) is a derivative of gallic acid and a potent antioxidant. In this study, we confirmed that MG treatment effectively inhibits lipid accumulation, which occurred mostly in the early stages of adipogenesis. We also showed that shortly after adipogenic induction, MG facilitated a G0/G1 cell cycle arrest. Mechanistic studies revealed that MG treatment inhibited ERK1/2 phosphorylation, which is a key regulator of the G1- to S-phase transition. Furthermore, MG treatment prevented the adipogenic hormonal stimuli-induced inhibition of the cyclin-dependent kinase inhibitor p27Kip1 . This led to inhibition of the transcription factor E2F1 by preventing the phosphorylation of, and thereby activation of its destruction partner RB. MG treatment also downregulated factors that are upstream of RB-E2F1 signaling such as Cdk2, Cyclin E, Cdk4, and Cyclin D1 where Cyclin D3 level was unaffected. We also found that MG treatment markedly decreased the expression and phosphorylation of C/EBPbeta, by phosphorylating, and therefore inactivating, GSK3beta, which is a prerequisite for its DNA binding capacity, and thereby mitotic clonal expansion (MCE). Ultimately, MG treatment downregulates key terminal adipogenic transcription factors including C/EBPalpha, PPARgamma, aP2 (Fabp4), and adiponectin. Moreover, MG also protects adipocytes from oxidative stress by alleviating intracellular reactive oxygen species and activating Nrf2, HO-1, and PRDX3. Thus, this study provides a mechanistic insight into the anti-adipogenic actions of MG. (c) 2016 BioFactors, 42(6):716-726, 2016. PMID- 27412173 TI - Maternal health inequalities and GP provision: investigating variation in consultation rates for women in the Born in Bradford cohort. AB - Background: The 'Five Year Forward View' (NHS England) calls for a radical upgrade in public health provision. Inequalities in maternal health may perpetuate general patterns of health inequalities across generations; therefore equitable access to general practice (GP) provision during maternity is important. This paper explores variation in GP consultation rates for disadvantaged mothers. Method: Data from the Born in Bradford cohort (around 12 000 women), combined with GP records and GP practice variables, were modelled to predict GP consultation rates, before and after adjusting for individual health and GP provision. Results: Observed GP consultation rates are higher for women in materially deprived neighbourhoods and Pakistani women. However these groups were found to consult less often after controlling for individual health. This difference, around one appointment per year, is 'explained' by the nature of GP provision. Women in practices with a low GP to patient ratio had around 09 fewer consultations over the six year period compared to women in practices with the highest ratio. Conclusions: Equitable access to GP services, particularly for women during the maternal period, is essential for tackling deep-rooted health inequalities. Future GP funding should take account of neighbourhood material deprivation to focus resources on areas of the greatest need. PMID- 27412174 TI - Intensity of physical activity and subjective well-being: an empirical analysis of the WHO recommendations. AB - Background: This study examined the effect of different intensities of physical activity and the recommendations of the World Health Organization (WHO) on the subjective well-being (SWB) of adults in two age groups (18-64; 65+). Methods: Cross-sectional survey data from 28 European countries were used for the analysis (n = 21 008). Participation intensity was measured with the number of days and minutes of light (walking), moderate and vigorous activity. Another three dummy variables reflected how the WHO guidelines were met. Two-stage least square models were estimated with life satisfaction (measuring SWB) as the dependent variable. Results: For 18- to 64-year-olds, walking (minutes and days/week) and vigorous activity (minutes/week) significantly added to SWB, while moderate activity (minutes/week) had a negative effect. Individuals in both age groups meeting the guidelines only for moderate activity and those meeting the guidelines for both moderate and vigorous activity or using a combination of both reported significantly higher well-being levels compared with those not meeting the guidelines. Conclusions: Physical activity recommendations aiming at improving individuals' mental health should reconsider the inclusion of light intensity activity, the interchangeability of moderate and vigorous activity, and the fact that more physical activity does not lead to better outcomes for all intensities and age groups. PMID- 27412176 TI - Understanding the urban-rural disparity in HIV and poverty nexus: the case of Kenya. AB - Background: The relationship between HIV and poverty is complex and recent studies reveal an urban-rural divide that is not well understood. This paper examines the urban-rural disparity in the relationship between poverty and HIV infection in Kenya, with particular reference to possible explanations relating to social cohesion/capital and other moderating factors. Methods: Multilevel logistic regression models are applied to nationally-representative samples of 13 094 men and women of reproductive age from recent Kenya Demographic and Health Surveys. Results: The results confirm a disproportionate higher risk of HIV infection among the urban poor, despite a general negative association between poverty and HIV infection among rural residents. Estimates of intra-community correlations suggest lower social cohesion in urban than rural communities. This, combined with marked socio-economic inequalities in urban areas is likely to result in the urban poor being particularly vulnerable. The results further reveal interesting cultural variations and trends. In particular, recent declines in HIV prevalence among urban residents in Kenya have been predominantly confined to those of higher socio-economic status. Conclusion: With current rapid urbanization patterns and increasing urban poverty, these trends have important implications for the future of the HIV epidemic in Kenya and similar settings across the sub-Saharan Africa region. PMID- 27412175 TI - Interactions between individual and perceived environmental factors on Latinas' physical activity. AB - Background: Latinas have disproportionately low levels of physical activity (PA) and the ecological correlates of their PA remain unclear. This study aims to test interactions between individual and environmental factors on Latinas' PA. Methods: We analyzed baseline data from 436 Latinas participating in a PA randomized controlled trial in San Diego, CA [Fe en Accion/Faith in Action]. Measures included demographics, perceived environment, PA and anthropometrics. Mixed effects models examined interactions between individual and environmental factors on self-reported leisure-time and transportation, and accelerometer assessed PA. Results: Significant positive associations were found between neighborhood aesthetics and leisure-time moderate-to-vigorous PA (MVPA) and between having destinations within walking distance from home and transportation PA (P < 0.05). We found significant interactions of income with aesthetics and sidewalk maintenance as well as between weight status and safety from crime. Favorable aesthetics was related to more leisure-time MVPA only among lower income women (odds ratio (OR) = 1.57; 95% confidence interval (CI): 1.18, 2.08); however, higher income women reporting better sidewalk maintenance reported more leisure-time MVPA (OR = 1.51; 95% CI: 1.06, 2.15). Higher perceived safety from crime was positively related to transportation PA only among overweight/obese women. Conclusions: Subgroup differences should be considered when developing interventions targeting the neighborhood environment to promote Latinas' PA. PMID- 27412177 TI - Knowledge, attitudes and awareness of the human papillomavirus amongst primary care practice nurses: an evaluation of current training in England. AB - Background: The incorporation of Human papillomavirus (HPV) testing into the English cervical screening programme has been met with fear and anxiety. Healthcare professionals need to be adequately informed about HPV to help alleviate patient concerns. The aim of this study was to evaluate the HPV training provided to practice nurses (PNs) and determine their level of HPV knowledge. Method: A web-based survey was distributed to 147 General Practice surgeries in the Leicester, Leicestershire and Rutland regions, between May and July 2015. The survey explored four broad areas; demographics/level of experience, HPV knowledge, attitudes towards the HPV vaccine and self-perceived adequacy of HPV knowledge. Results: A total of 128 surveys were completed, with 94 complete responses. Overall awareness of basic HPV facts was adequate; however, detailed, and in some cases basic, knowledge was lacking. 9.6% failed to identify that HPV can cause cervical cancer and 62.8% believed that HPV requires treatment. Not all PNs felt adequately informed about HPV and a need to improve the provision of training was identified. Conclusion: PNs play a key role in increasing public awareness of HPV and implementing cervical cancer screening. The provision of education to PNs needs to be a priority and current methods of training need to be re-evaluated. PMID- 27412178 TI - Publication ethics in public health emergencies. AB - In this article, we describe and analyse three issues in publication ethics that are raised when conducting research in emergencies and disasters. These include reluctance to share data and samples because of concerns about publications, loss of individual authorship in high high-profile multi-entity publications, and the deaths of authors during dangerous research projects. An emergency research pledge may be useful in avoiding some of these issues. PMID- 27412180 TI - Advert. PMID- 27412179 TI - The impact of an HIV/AIDS adult integrated health program on leaving hospital against medical advice among HIV-positive people who use illicit drugs. AB - Background: Leaving hospital against medical advice (AMA) is a major source of avoidable morbidity, mortality and healthcare expenditure. The objective of this study was to assess the impact of an innovative HIV/AIDS adult integrated health program on leaving hospital AMA among HIV-positive people who use illicit drugs (PWUD). Methods: Using generalized estimating equations, we examined the relationship between being a participant of the Dr. Peter Centre (DPC), a specialty HIV/AIDS-focused adult integrated health program, and leaving hospital AMA among a cohort of HIV-positive PWUD patients. Results: Between July 2005 and July 2011, 181 HIV-positive PWUD who experienced >=1 hospitalization were recruited into the study. Of the 406 hospital admissions among these individuals, 73 (39.9%) participants left the hospital AMA. In a multivariable model adjusted for confounders, being a participant of the DPC was independently associated with lower odds of leaving hospital AMA (adjusted odds ratio = 0.42; 95% confidence interval: 0.19-0.89). Conclusions: Our findings suggest that the provision of a broad range of clinical, harm reduction and support services through an innovative HIV/AIDS-focused adult integrated health program operating in proximity to a hospital may curb the rate at which individuals leave hospital prematurely. PMID- 27412181 TI - Advert. PMID- 27412182 TI - Society Officers. PMID- 27412185 TI - Extracting Complex Refractive Index from Polycrystalline Glucose with Self Referenced Method for Terahertz Time-Domain Reflection Spectroscopy. AB - A self-referenced method for extracting the complex refractive index of material was proposed. The method utilized signals reflected from the front and rear surfaces of a slice sample as reference and sample signals, respectively. Before using the self-referenced method, a hybrid filtering technique for eliminating systematic and random noises of time-domain terahertz reflection spectroscopy was used. A terahertz reflection spectrum of crystalline glucose was measured and three feature absorption peaks were obtained from 0.2 to 2.0 THz. We suggest that intermolecular vibrational modes may contribute to the observed absorption spectra in the THz frequency range. PMID- 27412186 TI - Forensic Hair Differentiation Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy. AB - Hair and fibers are common forms of trace evidence found at crime scenes. The current methodology of microscopic examination of potential hair evidence is absent of statistical measures of performance, and examiner results for identification can be subjective. Here, attenuated total reflection (ATR) Fourier transform-infrared (FT-IR) spectroscopy was used to analyze synthetic fibers and natural hairs of human, cat, and dog origin. Chemometric analysis was used to differentiate hair spectra from the three different species, and to predict unknown hairs to their proper species class, with a high degree of certainty. A species-specific partial least squares discriminant analysis (PLSDA) model was constructed to discriminate human hair from cat and dog hairs. This model was successful in distinguishing between the three classes and, more importantly, all human samples were correctly predicted as human. An external validation resulted in zero false positive and false negative assignments for the human class. From a forensic perspective, this technique would be complementary to microscopic hair examination, and in no way replace it. As such, this methodology is able to provide a statistical measure of confidence to the identification of a sample of human, cat, and dog hair, which was called for in the 2009 National Academy of Sciences report. More importantly, this approach is non-destructive, rapid, can provide reliable results, and requires no sample preparation, making it of ample importance to the field of forensic science. PMID- 27412187 TI - Laser Scanning-Assisted Tip-Enhanced Optical Microscopy for Robust Optical Nanospectroscopy. AB - Laser-scanning-assisted tip-enhanced optical microscopy was developed for robust optical nanospectroscopy. The laser-scanning system was utilized to automatically set and keep the center of a tight laser-focusing spot in the proximity of a metallic tip with around 10 nm precision. This enabled us to efficiently and stably induce plasmon-coupled field enhancement at the apex of the metallic probe tip. The laser-scanning technique was also applied to tracking and compensating the thermal drift of the metallic tip in the spot. This technique is usable for long-term tip-enhanced optical spectroscopy without any optical degradation. PMID- 27412188 TI - Effects of early blood pressure reduction on cognitive function in patients with acute ischemic stroke. AB - BACKGROUND: The effect of early blood pressure reduction on cognitive function in patients with acute ischemic stroke remains unknown. AIM: We tested whether antihypertensive treatment would reduce cognitive impairment in patients with acute ischemic stroke. METHODS: In the China Antihypertensive Trial in Acute Ischemic Stroke, patients with elevated blood pressure were randomly assigned to receive antihypertensive treatment or to discontinue all hypertensive medications within 48 h of onset. Cognitive function was measured by the Mini-Mental State Examination and Montreal Cognitive Assessment at 3 months after randomization in a subsample of 638 participants. RESULTS: Mean systolic blood pressure was reduced by 21.5 mmHg in the antihypertensive treatment group and 13.9 mmHg in the control group within 24 h after randomization (P < 0.001). Mean systolic blood pressure was 134.9 mmHg in the antihypertensive treatment group and 141.6 mmHg in the control group at day 14 after randomization (P < 0.001). Median Mini-Mental State Examination score was 26 and Montreal Cognitive Assessment score was 22 in both the antihypertensive treatment and control groups at 3 months. An Mini Mental State Examination < 24 was present in 30.9% of patients in the antihypertensive treatment group compared with 29.7% in the control group (odds ratio = 1.06; 95% confidence interval 0.75-1.48; P = 0.75). Likewise, proportions of patients with Montreal Cognitive Assessment < 26 were similar between the antihypertensive treatment (70.6%) and control (70.7%) groups (odds ratio = 0.99; 95% confidence interval 0.70-1.40; P = 0.96). CONCLUSIONS: These data indicated that early blood pressure reduction with antihypertensive medication in patients with acute ischemic stroke had no effect on cognitive impairment at 3 months. PMID- 27412189 TI - Changes in the prevalence of hospitalization and comorbidity in US adults with stroke: A three decade cross-sectional and birth cohort analysis. AB - BACKGROUND AND PURPOSE: Little attention was paid to the transition of care for stroke that may partially explain the long-term trend of stroke rates. We aimed to test the trend of hospitalization attributable to stroke in US adults. METHODS: Data from National Hospital Discharge Surveys 1980-2010 in patients aged >=18 (n = 6,527,304) were analyzed to examine the trend of patients with first list diagnoses of stroke. Stroke comorbidities were classified in stroke patients with second- to seven-listed diagnoses of coronary heart disease, hypertension, diabetes, arrhythmias, or hyperlipidemia. Stroke trends by survey years and birth cohorts were analyzed using univariate, multivariate, and birth cohorts methods. RESULTS: Of the total study sample, the prevalence of hospitalization due to stroke was 22.99%, 30.00%, and 27.03% in years of 1980-1989, 1990-1999, and 2000 2010 in males, and 17.30%, 22.04%, and 19.34% in females, respectively. Overall, hospitalization rates in stroke patients significantly increased among adults aged <65, and decreased in adults aged >=65. There was an increase in stroke hospitalization rate in the old adults aged >=65 in recent birth cohorts. Significant increased trends of comorbid hypertension, diabetes, arrhythmias, and hyperlipidemia were observed from 1980 to 2010. CONCLUSION: A significant increase in stroke hospitalization rate was observed in adults aged <65 in the past three decades, and in old adults in recent years. Increases in stroke comorbidity rates were observed in all age groups. Findings from the study highlight that both public health and clinical practices face a serious challenge in controlling this unwelcome increased stroke trend. PMID- 27412190 TI - Measuring non-vitamin K antagonist oral anticoagulant levels: When is it appropriate and which methods should be used? AB - BACKGROUND: Although the need for an emergency intervention may merit laboratory measurement of non-vitamin K antagonist oral anticoagulant (NOAC) concentration or anticoagulant activity, NOACs are not supposed to require routine monitoring due to their stable pharmacological profiles compared with warfarin. AIMS: To examine situations where NOAC measurement may be useful and to provide information about methodologies available to measure NOAC-related anticoagulation activity. SUMMARY OF REVIEW: The routine coagulation tests, including prothrombin time, thrombin time, activated partial thromboplastin time, and international normalized ratio, have variable sensitivities to NOACs. Tests have been developed for use with specific NOACs, e.g. diluted thrombin time or chromogenic factor Xa assays. In emergency situations, such as severe bleeding, stroke, or a requirement for urgent surgery or procedures, there may be a need to assess anticoagulant activity to guide clinical decision making. In cases where neutralization of the anticoagulant effect is warranted, specific reversal agents are likely to become invaluable medical tools. Evidence to date suggests that dosing decisions for NOACs based on clinical features (e.g. age or renal function) can help optimize the benefit-risk balance without assessment of anticoagulant activity in non-emergency routine situations. CONCLUSIONS: Regular monitoring of NOAC levels does not provide benefits and cannot be recommended at present. In some specific circumstances, e.g. severe bleeding, before urgent surgery, or before thrombolysis, measurement may be beneficial to assess whether a patient is actively anticoagulated. The availability of NOAC-specific reversal agents may change management practices in emergencies. PMID- 27412191 TI - Air, rail and road: Medical Guidelines for Employees with a History of Cerebrovascular Disease. AB - Background An acute medical condition following a previous stroke among those who operate trains, airplanes, and commercial vehicles can result in serious accidents. There are guidelines in place to assist physicians and employers in assessing the risks of returning to work after stroke but the extent and comprehensiveness across nations and among safety-critical occupations are not widely known. Methods Medical guidelines currently in place to regulate safety critical occupations including railway engineers, pilots and commercial vehicle drivers were systematically reviewed. Electronic and hand literature searches as well as review of grey literature for Canada, the USA, the UK, and Australia were conducted. Results There is no consistent set of guidelines that address the risk of a second catastrophic event after an initial cerebrovascular event in those employed in safety critical occupations in the four countries assessed. Some broad principles existed between the different countries and occupations but there was major variation in the approach to cerebrovascular disease and its impact on those working in safety-critical occupations. Conclusions A synthesis of current knowledge would assist in establishing risks of a catastrophic event in those who have already suffered from cerebrovascular illness. This will allow the creation of medical guidelines which could be applied to any safety critical occupation in any nation. PMID- 27412192 TI - A multicenter, randomized trial on neuroprotection with remote ischemic per conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol. AB - Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5 25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm3 in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke. PMID- 27412193 TI - Pheromone Lure and Trap Color Affects Bycatch in Agricultural Landscapes of Utah. AB - Aerial traps, using combinations of color and attractive lures, are a critical tool for detecting and managing insect pest populations. Yet, despite improvements in trap efficacy, collection of nontarget species ("bycatch") plagues many insect pest surveys. Bycatch can influence survey effectiveness by reducing the available space for target species and increasing trap screening time, especially in areas where thousands of insects are captured as bycatch in a given season. Additionally, bycatch may negatively impact local nontarget insect populations, including beneficial predators and pollinators. Here, we tested the effect of pheromone lures on bycatch rates of Coccinellidae (Coleoptera), Apoidea (Hymenoptera), and nontarget Lepidoptera. Multicolored (primarily yellow and white) bucket traps containing a pheromone lure for capturing one of three survey target species, Spodoptera litura (F.), S. littoralis (Boisduval), or Helicoverpa armigera (Hubner), were placed in alfalfa and corn fields, and compared to multicolored traps without a pheromone lure. All-green traps with and without H. armigera lures were employed in a parallel study investigating the effect of lure and trap color on bycatch. Over 2,600 Coccinellidae representing seven species, nearly 6,400 bees in 57 species, and >9,000 nontarget moths in 17 genera were captured across 180 traps and seven temporal sampling events. Significant effects of lure and color were observed for multiple taxa. In general, nontarget insects were attracted to the H. armigera lure and multicolored trap, but further studies of trap color and pheromone lure specificity are needed to better understand these interactions and to minimize nontarget captures. PMID- 27412194 TI - Developmental Acclimation of Drosophila suzukii (Diptera: Drosophilidae) and Its Effect on Diapause and Winter Stress Tolerance. AB - We investigated the influence of developmental conditions on adult morphology, reproductive arrest, and winter stress tolerance of the invasive pest of small fruit, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae). Cooler rearing temperatures (15 degrees C) resulted in larger, darker "winter morph" (WM) adults than "summer morph" flies reared at optimal temperatures (25 degrees C). Abdominal pigmentation scores and body size measurements of laboratory-reared WMs were similar to those of D. suzukii females captured in late autumn in Geneva, NY. We evaluated reproductive diapause and cold hardiness in live-captured D. suzukii WMs as well as WMs reared in the laboratory from egg to adult under four developmental conditions: static cool temperatures (SWM; 15 degrees C, 12:12 h L:D), fluctuating temperatures (FWM; 20 degrees C L: 10 degrees C D, 12:12 h L:D), and static cool temperatures (15 degrees C, 12:12 h L:D) followed by posteclosion chilling (CWM; 10 degrees C) under short-day (SD; 12:12 h L:D) or long-day photoperiods (LD; 16:8 h L:D). Live-captured D. suzukii WMs and CWMs had longer preoviposition times than newly eclosed summer morph adults, indicating a reproductive diapause that was not observed in SWMs or FWMs. Additionally, recovery after acute freeze stress was not different between CWM-SD females and live captured WM females. More 7-d-old CWMs survived 0, -1, or - 3 degrees C freeze stress than summer morph adults, and more CWM-SD adults survived -3 degrees C freeze stress than CWM-LD adults. Survival after -3 degrees C freeze stress was significantly higher in diapausing, CWMs than nondiapausing SWMs and FWMs. PMID- 27412195 TI - Developing a Media Moisture Threshold for Nurseries to Reduce Tree Stress and Ambrosia Beetle Attacks. AB - Exotic ambrosia beetles are among the most damaging pests of trees grown in nurseries. The primary pests Xylosandrus crassiusculus Motschulsky and Xylosandrus germanus Blandford use ethanol to locate vulnerable trees. Research, primarily with X. germanus, has shown that flood-stressed trees emit ethanol and are preferentially attacked by ambrosia beetles. Our goal was to develop a media (also called potting soil) moisture threshold as an integrated pest management (IPM) tactic and assess grower practices that lead to ambrosia beetle attacks. Flooded Cornus florida L., Cornus kousa Burg., and Magnolia grandiflora L. trees incurred more attacks than unflooded trees that were not attacked. To determine optimal media moisture levels, we grew flood-tolerant Acer rubrum L. and flood intolerant C. florida in containers with 10, 30, 50, 70, or 90% media moisture. No flooded or unflooded A. rubrum were attacked. However, C. florida grown in 70 or 90% moisture were attacked and died, whereas trees at 30 and 50% moisture were not attacked. Thus, we suggest an upper moisture threshold of 50% when growing C. florida and other flood-intolerant trees. However, during peak ambrosia beetle flight activity in spring 2013 and 2014, we found that media moisture levels in commercial nurseries were often between 50 and 90%. Implementing a media moisture threshold, as a new IPM tool, could reduce ambrosia beetle attacks and the need for insecticide applications, which is currently the only available management tactic. Future research should focus on how changes in substrates, irrigation, and other practices could help growers meet this threshold. PMID- 27412196 TI - Pregnant pause. PMID- 27412197 TI - [Matiere a reflexion sur la maternite]. PMID- 27412198 TI - Social accountability at the meso level: Into the community. PMID- 27412199 TI - Toward a comprehensive management strategy for incidental findings in imaging. PMID- 27412200 TI - National pharmacare: Time to move forward. PMID- 27412201 TI - [Responsabilite sociale au mesoniveau: Au sein de la communaute]. PMID- 27412202 TI - Analogy does not apply. PMID- 27412203 TI - Medicine is a business. PMID- 27412204 TI - Professionals, not employees. PMID- 27412205 TI - Create a better system. PMID- 27412206 TI - Approach to lymphogranuloma venereum. AB - OBJECTIVE: To review the literature about lymphogranuloma venereum (LGV) and to provide an overview and discussion of practice guidelines. SOURCES OF INFORMATION: The terms Chlamydia trachomatis and lymphogranuloma venereum were searched separately in PubMed. Empirical studies, practice reviews, and clinical guidelines were included. All reference lists were reviewed for additional articles. MAIN MESSAGE: Since 2003, there has been a resurgence of LGV among men who have sex with men in many Western countries, including Canada. Although LGV is a serovar of Chlamydia trachomatis (serovar L), it can invade regional lymph nodes, and consequently presents with different symptoms than the other subtypes of chlamydia (serovars A through K). Specifically, LGV transitions through 3 phases: a painless papule or ulcer at the site of inoculation; invasion of the regional lymph nodes, which can present with an inguinal or rectal syndrome; and irreversible destruction of lymph tissue. In contrast, chlamydia serovars A to K exclusively produce superficial mucosal infections. Lymphogranuloma venereum also requires a different treatment regimen than other chlamydia serovars. CONCLUSION: In light of the current resurgence of LGV, its unique symptoms and clinical course, and its requirement for a different treatment than other chlamydia serovars, it is important for primary care providers to recognize when LGV should be included as an appropriate differential diagnosis. PMID- 27412208 TI - Collaboration with a midwife in the care of a pregnant patient with recurrent genital herpes simplex virus. PMID- 27412207 TI - Intranasal midazolam for seizure cessation in the community setting. AB - QUESTION: There are times when parents arrive to my clinic after their child has had a seizure and a second seizure takes place in the clinic. While waiting for transport to the hospital, are there ways to stop the seizures without the need to obtain intravenous access in the clinic? ANSWER: Intravenous diazepam has been a first-line therapy to stop seizures in children for many years. Other routes of drug administration such as intramuscular, rectal, and buccal are available but have several limitations. More evidence suggests that the intranasal route to administer drugs is quick and effective in children, and the use of midazolam has been continuing to show promise in seizure cessation. With its good safety profile, intranasal midazolam can be used in the clinic and prehospital setting for seizure cessation in children. PMID- 27412210 TI - Choosing Wisely Canada recommendations. PMID- 27412209 TI - Tale of 2 pregnancies: Heterotopic pregnancy in a spontaneous cycle. PMID- 27412211 TI - Electrolyte disturbance with diuretics and ACEIs. PMID- 27412212 TI - Office-based frenotomy for ankyloglossia and problematic breastfeeding. PMID- 27412213 TI - Late-night breastfeeding advice. PMID- 27412214 TI - The missing of mums and babes: Addressing Canada's rural maternity care crisis. PMID- 27412215 TI - Promoting high-quality feedback: Tool for reviewing feedback given to learners by teachers. PMID- 27412216 TI - Supporting primary care public health functions. PMID- 27412217 TI - [Appui aux fonctions de sante publique en soins primaires]. PMID- 27412218 TI - Reflecting on family medicine. PMID- 27412219 TI - [Reflexion sur la medecine familiale]. PMID- 27412220 TI - [La globalite des soins]. PMID- 27412221 TI - Comprehensiveness of care. PMID- 27412222 TI - [Vers une strategie de prise en charge complete des detections fortuites en imagerie]. PMID- 27412223 TI - [Assurance-medicaments nationale: Le moment d'aller de l'avant]. PMID- 27412224 TI - [Recommandations de Choisir avec soin Canada]. PMID- 27412225 TI - [Disparition des meres et des enfants: Regler la crise des soins de maternite en regions rurales canadiennes]. PMID- 27412226 TI - [Promouvoir une retroaction de grande qualite: Outil d'examen de la retroaction donnee aux apprenants par les enseignants]. PMID- 27412227 TI - Introduction to special issue on The Role of Connectivity in Developmental Disorders: Genetic and Neural Network Approaches. PMID- 27412228 TI - A theoretical rut: revisiting and critically evaluating the generalized under/over-connectivity hypothesis of autism. AB - In 2004, two papers proposed that pervasive functional under-connectivity (Just et al., ) or a trade-off between excessive local connectivity at the cost of distal under-connectivity (Belmonte et al., ) characterizes atypical brain organization in autism. Here, we take stock of the most recent and rigorous functional and structural connectivity findings with a careful eye toward evaluating the extent to which they support these original hypotheses. Indeed, the empirical data do not support them. From rsfMRI studies in adolescents and adults, there is an emerging consensus regarding long-range functional connections indicating cortico-cortical under-connectivity, specifically involving the temporal lobes, combined with subcortical-cortical over connectivity. In contrast, there is little to no consensus regarding local functional connectivity or findings from task-based functional connectivity studies. The structural connectivity data suggest that white matter tracts are pervasively weak, particularly in the temporal lobe. Together, these findings are revealing how deeply complex the story is regarding atypical neural network organization in autism. In other words, distance and strength of connectivity as individual factors or as interacting factors do not consistently explain the patterns of atypical neural connectivity in autism. Therefore, we make several methodological recommendations and highlight developmental considerations that will help researchers in the field cultivate new hypotheses about the nature and mechanisms of potentially aberrant functional and structural connectivity in autism. PMID- 27412230 TI - Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach. AB - Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype. PMID- 27412229 TI - Reading skill-fractional anisotropy relationships in visuospatial tracts diverge depending on socioeconomic status. AB - Low socioeconomic status (SES) has been repeatedly linked with decreased academic achievement, including lower reading outcomes. Some lower SES children do show skills and scores commensurate with those of their higher SES peers, but whether their abilities stem from the same systems as high SES children or are based on divergent strategies is unknown. We here investigated a potential interactive relationship between SES and real-word reading skill in the white matter in 42 typically developing children. SES was determined based on parental education; reading skill and age were not significantly related to SES. There was a significant neural interaction: Clusters in the bilateral inferior longitudinal fasciculus (ILF), left superior longitudinal fasciculus, and left corticospinal tract demonstrated interactive skill-SES relationships in fractional anisotropy. Follow-up analyses demonstrated that higher SES children showed a positive relationship between fractional anisotropy, reflecting tract coherence, and reading skill in left hemisphere tract clusters, whereas lower SES children showed a positive relationship in the right hemisphere homologues. Broadly, the ILF has been demonstrated to support orthographic skill on the left and more general visuospatial processing on the right, so high reading achievement in lower SES children may rely on supplementary visuospatial processing more than for higher SES readers. This pattern is consistent with previous work reporting low SES children's environments to include less rich verbal experience, which may lead them to disproportionately draw on visuospatial skills for success. Further, these results indicate that group SES differences may be best described by an adaptive, not a deficit, model. PMID- 27412232 TI - Oncogenic KRAS triggers MAPK-dependent errors in mitosis and MYC-dependent sensitivity to anti-mitotic agents. AB - Oncogenic KRAS induces cell proliferation and transformation, but little is known about its effects on cell division. Functional genetic screens have recently revealed that cancer cell lines expressing oncogenic KRAS are sensitive to interference with mitosis, but neither the mechanism nor the uniformity of anti mitotic drug sensitivity connected with mutant KRAS expression are yet clear. Here, we report that acute expression of oncogenic KRAS in HeLa cells induces mitotic delay and defects in chromosome segregation through mitogen-activated protein kinase (MAPK) pathway activation and de-regulated expression of several mitosis-related genes. These anomalies are accompanied by increased sensitivity to anti-mitotic agents, a phenotype dependent on the transcription factor MYC and its downstream target anti-apoptotic protein BCL-XL. Unexpectedly, we find no correlation between KRAS mutational status or MYC expression levels and anti mitotic drug sensitivity when surveying a large database of anti-cancer drug responses. However, we report that the co-existence of KRAS mutations and high MYC expression predicts anti-mitotic drug sensitivity. Our findings reveal a novel function of oncogenic KRAS in regulating accurate mitotic progression and suggest new avenues to therapeutically target KRAS-mutant tumours and stratify patients in ongoing clinical trials of anti-mitotic drugs. PMID- 27412233 TI - Notes of robotic surgical technique: four ways to mobilize splenic flexure. AB - Splenic flexure mobilization is a challenging surgical procedure, but is it necessary to safely perform left colon and rectal resections. This paper is a technical focus detailing the four ways to mobilize splenic flexure in robotic surgery. The medial approach involves an extensive dissection of the medial plane separating descending mesocolon form Toldt fascia; the sovramesocolic approach starts with gastrocolic ligament section; the lateral approach starts with coloparietal detachment and the "one inch-one inch" approach starts with section of transverse mesocolon. PMID- 27412234 TI - Metastatic tumors to the pancreas: a systematic review and meta-analysis. AB - INTRODUCTION: Metastases to the pancreas from other primary tumors are increasingly recognized in clinical practice, but the real role of surgery remains unclear. This study was designated to evaluate by a meta-analytic approach the results of surgical treatment for the most common malignancies metastasizing to the pancreas. EVIDENCE ACQUISITION: MEDLINE, PubMED, Scopus and Web of Sciences were searched from January 2000 to December 2015. Studies reporting postoperative complications, postoperative mortality, disease-free and overall survival of patients undergoing resection for secondary tumours of the pancreas, were included. EVIDENCE SYNTHESIS: Fourteen publication with 281 patients met the inclusion criteria and were subjected to the analysis. Operative morbidity and mortality were 34% and 1.3% respectively. Pancreatic resection for renal cell cancer showed better survival compared to other non-renal cell cancer (ratio of mean 1.83; 95% CI: 1.42-2.36, I2=74.52%, P<0.001). Disease-free interval was longer for metastatic renal cell carcinoma patients (mean difference 6.36, 95% CI: 3.803-8.912 years, I2=76:54%, P<0.001). A meta-regression was used to correlate the two endpoints and showed that a longer DFI is associated to a longer survival. CONCLUSIONS: Pancreatic resection for metastasis should be reserved to patients in good health conditions, with isolated disease from renal cell cancer. For other types of tumor, surgery should be performed only in individual basis. There is a need of studies evaluating the role of chemotherapy in the neoadjuvant setting or the best sequential use of multimodality treatment (targeted therapy, radiotherapy, surgery, etc.). PMID- 27412235 TI - Xanthoceras sorbifolia extracts ameliorate dendritic spine deficiency and cognitive decline via upregulation of BDNF expression in a rat model of Alzheimer's disease. AB - Xanthoceras sorbifolia, a traditional Chinese folk medicine with anti inflammatory effects, has been used for a long time in China, especially in the Inner Mongolian area for the treatment of rheumatism. Inflammation is one of the main causes of Alzheimer's disease (AD). AD is characterized by aggregation of amyloid beta-peptide (Abeta) plaques, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. To investigate whether Xanthoceras sorbifolia extracts (XSE) improve cognition and protect dendritic spines, we performed behavioral tests to investigate learning and memory in an Abeta25-35-induced dementia animal model of AD as well as Golgi staining to observe dendritic spine formation in CA1 pyramidal neurons and western blots to test the expression levels of PSD95, BDNF and downstream signaling pathways. Our results indicated that oral treatment with XSE significantly reduced cognitive impairments in behavioral tests (passive avoidance test, novel object recognition test, Y-maze test and Morris water maze test). Golgi staining results revealed that XSE ameliorated dendritic spine density deficits in CA1 pyramidal neurons in the hippocampus. Western blot analysis suggested that XSE upregulated PSD95, which is the major scaffolding protein in synapses. BDNF levels and the ratio of p TrkB/TrkB increased, and the expression of the RhoA, a member of the Rho-GTPase family, and its downstream target protein ROCK2 decreased in the dementia animal model following treatment with XSE. Therefore, the cognition-improving effects of XSE probably resulted from dendritic spine protection effects through regulation of BDNF signaling pathways. PMID- 27412236 TI - Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes. AB - Mutations in parkin cause autosomal recessive Parkinsonism and mitochondrial defects. A recent drug screen identified a class of steroid-like hydrophobic compounds able to rescue mitochondrial function in parkin-mutant fibroblasts. Whilst these possess therapeutic potential, the size and high hydrophobicity of some may limit their ability to penetrate the blood-brain barrier from systemic circulation, something that could be improved by novel drug formulations. In the present study, the steroid-like compounds Ursolic Acid (UA) and Ursocholanic Acid (UCA) were successfully encapsulated within nanoscopic polymersomes formed by poly(2-(methacryloyloxy)ethyl phosphorylcholine)-poly(2-di-isopropylamino)ethyl methacrylate) (PMPC-PDPA) and separated into spherical and tubular morphologies to assess the effects of nanoparticle mediated delivery on drug efficacy. Following incubation with either morphology, parkin-mutant fibroblasts demonstrated time and concentration dependent increases in intracellular ATP levels, resembling those resulting from treatment with nascent UA and UCA formulated in 0.1% DMSO, as used in the original drug screen. Empty PMPC-PDPA polymersomes did not alter physiological measures related to mitochondrial function or induce cytotoxicity. In combination with other techniques such as ligand functionalisation, PMPC-PDPA nanoparticles of well-defined morphology may prove a promising platform for tailoring the pharmacokinetic profile and organ specific bio-distribution of highly hydrophobic compounds. PMID- 27412237 TI - CORM-2 inhibits TXNIP/NLRP3 inflammasome pathway in LPS-induced acute lung injury. AB - OBJECTIVE: Accumulated studies suggest that exogenously administered carbon monoxide is beneficial for the resolution of acute lung inflammation. The present study aimed to examine the effects and the underlying mechanisms of CORM-2 on thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: ALI was intratracheally induced by LPS in C57BL6 mice. CORM-2 or iCORM-2 (30mg/kg i.p.) was administered immediately before LPS instillation. 6 h later, lung bronchoalveolar lavage (BAL) fluids were acquired for IL-18, IL-1beta, and cell measurement, and lung issues were collected for histologic examination, wet/dry weight ratio, and determination of TXNIP/NLRP3 inflammasome expression, NLRP3 inflammasome and NF-KappaB activity, and reactive oxygen species (ROS) production. RESULTS: LPS triggered significant lung edema, lung injury, and leukocyte infiltration, and elevated the levels of IL-1beta and IL-18 in lung BAL fluids. CORM-2 pretreatment resulted in a marked amelioration of lung injury and reduced IL-1beta and IL-18 secretion in BAL fluids. In lung tissues; CORM-2 down regulated mRNA and protein level of TXNIP, NLRP3, ASC, and caspase-1. Furthermore, CORM-2 reduced ROS production, inhibited NLRP3 inflammasome and NF kappaB activity, and interaction of TXNIP-NLRP3. However, no significant differences were detected between the LPS and iCORM-2 (an inactive variant of CORM-2) group. CONCLUSION: CORM-2 suppresses TXNIP/NLRP3 inflammasome pathway and protects against LPS-induced lung injury. PMID- 27412238 TI - On the use of composite analyses to form physical hypotheses: An example from heat wave - SST associations. AB - This paper highlights some caveats in using composite analyses to form physical hypotheses on the associations between environmental variables. This is illustrated using a specific example, namely the apparent links between heat waves (HWs) and sea surface temperatures (SSTs). In this case study, a composite analysis is performed to show the large-scale and regional SST conditions observed during summer HWs in Perth, southwest Australia. Composite results initially point to the importance of the subtropical South Indian Ocean, where physically coherent SST dipole anomalies appear to form a necessary condition for HWs to develop across southwest Australia. However, sensitivity tests based on pattern correlation analyses indicate that the vast majority of days when the identified SST pattern appears are overwhelmingly not associated with observed HWs, which suggests that this is definitely not a sufficient condition for HW development. Very similar findings are obtained from the analyses of 15 coupled climate model simulations. The results presented here have pertinent implications and applications for other climate case studies, and highlight the importance of applying comprehensive statistical approaches before making physical inferences on apparent climate associations. PMID- 27412239 TI - Paper-based sensors and assays: a success of the engineering design and the convergence of knowledge areas. AB - This review shows the recent advances and state of the art in paper-based analytical devices (PADs) through the analysis of their integration with microfluidics and LOC micro- and nanotechnologies, electrochemical/optical detection and electronic devices as the convergence of various knowledge areas. The important role of the paper design/architecture in the improvement of the performance of sensor devices is discussed. The discussion is fundamentally based on MUPADs as the new generation of paper-based (bio)sensors. Data about the scientific publication ranking of PADs, illustrating their increase as an experimental research topic in the past years, are supplied. In addition, an analysis of the simultaneous evolution of PADs in academic lab research and industrial commercialization highlighting the parallelism of the technological transfer from academia to industry is displayed. A general overview of the market behaviour, the leading industries in the sector and their commercialized devices is given. Finally, personal opinions of the authors about future perspectives and tendencies in the design and fabrication technology of PADs are disclosed. PMID- 27412240 TI - Wetting and orientation of catalytic Janus colloids at the surface of water. AB - Janus colloidal particles show remarkable properties in terms of surface activity, self-assembly and wetting. Moreover they can perform autonomous motion if they can chemically react with the liquid in which they are immersed. In order to understand the self-propelled motion of catalytic Janus colloids at the air water interface, wetting and the orientation of the catalytic surface are important properties to be investigated. Wetting plays a central role in active motion since it determines the contact between the fuel and the catalytic surface as well as the efficiency of the transduction of the chemical reaction into motion. Active motion is not expected to occur either when the catalytic face is completely out of the aqueous phase or when the Janus boundaries are parallel to the interfacial plane. The design of a Janus colloid possessing two hydrophilic faces is required to allow the catalytic face to react with the fuel (e.g. H2O2 for platinum) in water and to permit some rotational freedom of the Janus colloid in order to generate propulsion parallel to the interfacial plane. Here, we discuss some theoretical aspects that should be accounted for when studying Janus colloids at the surface of water. The free energy of ideal Janus colloidal particles at the interface is modeled as a function of the immersion depth and the particle orientation. Analytical expressions of the energy profiles are established. Energetic aspects are then discussed in relation to the particle's ability to rotate at the interface. By introducing contact angle hysteresis we describe how the effects of contact line pinning modifies the scenario described in the ideal case. Experimental observations of the contact angle hysteresis of Janus colloids at the interface reveal the effect of pinning; and orientations of silica particles half covered with a platinum layer at the interface do not comply with the ideal scenarios. Experimental observations suggest that Janus colloids at the fluid interface behave as a kinetically driven system, where the contact line motion over the defects decorating the Janus faces rules the orientation and rotational diffusion of the particle. PMID- 27412241 TI - Antitumour responses induced by a cell-based Reovirus vaccine in murine lung and melanoma models. AB - BACKGROUND: The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials. It has been shown to induce immune responses to tumours with very low toxicities. METHODS: In this study, Reovirus was examined in two main approaches in vivo, in mice, using the melanoma B16F10 and Lewis Lung Carcinoma (LLC) models. Initially, mice were treated intratumourally (IT) with Reovirus and the immune responses determined by cytokine analysis. Mice were also vaccinated using a cell-based Reovirus vaccine and subsequently exposed to a tumourigenic dose of cells (B16F10 or LLC). Using the same cell-based Reovirus vaccine, established tumours were treated and subsequent immune responses and virus retrieval investigated. RESULTS: Upregulation of several cytokines was observed following treatment and replication-competent virus was also retrieved from treated tumours. Varying levels of cytokine upregulation were observed and no replication-competent virus was retrieved in vaccine-treated mice. Prolongation of survival and delayed tumour growth were observed in all models and an immune response to Reovirus, either using Reovirus alone or a cell-based vaccine was also observed in all mice. CONCLUSION: This study provides evidence of immune response to tumours using a cell-based Reovirus vaccine in both tumour models investigated, B16F10 and LLC, cytokine induction was observed with prolongation of survival in almost all cases which may suggest a new method for using Reovirus in the clinic. PMID- 27412242 TI - Time trends: a ten-year comparison (2005-2015) of pedometer-determined physical activity and obesity in Czech preschool children. AB - BACKGROUND: To explore the time trends (2005-2015) of pedometer-determined weekday and weekend physical activity (PA) and obesity prevalence in 4-7-year-old Czech preschool children and changes in proportion of kindergarten vs. leisure time PA. METHODS: The study compared data of two cross-sectional cohorts of preschool children (2005: 92 boys and 84 girls; 2015: 105 boys and 87 girls) in the Czech Republic, using the same measurements and procedures in both cases. PA was monitored by the Yamax Digiwalker SW-200 pedometer for at least eight continuous hours a day over seven consecutive days. Body weight and height were measured using calibrated Tanita scales and anthropometry. The analysis of variance was conducted to examine the gender and cohort effect on step counts. The t-test was used to examine the difference in step counts in kindergarten (or leisure-time) between non-obese and obese children, and the chi-square test compared the prevalence of obesity between 2005 and 2015. RESULTS: The steps/day (mean +/- standard deviation) of preschoolers was significantly higher (p < 0.05) in 2015 (11,739 +/- 4,229 steps/day) than in 2005 (10,922 +/- 3,181 steps/day); and (p < 0.001) in boys (11,939 +/- 3,855 steps/day) than in girls (10,668 +/- 3,587 steps/day). In 2015, girls, but not boys, had a significantly (p < 0.01) greater step count on weekdays than in 2005, but not at weekends. A decline of leisure-time step counts on weekdays between 2005 and 2015 in girls (6,8652005 vs. 6,0592015, p < 0.01) and boys (7,8612005 vs. 6,4362015, p < 0.001) is compensated for by the increase of step counts in kindergarten (girls: 3,0582005 vs. 5,3302015, and boys: 4,0032005 vs. 5,9992015, p < 0.001). The prevalence of obesity was not significantly different either in 2005 or 2015 among preschool girls (7.14 % 2005 vs. 9.20 % 2015) or boys (6.52 % 2005 vs. 9.52 % 2015). CONCLUSION: The steps/day of preschoolers was higher in 2015 than in 2005; this higher level of PA was the result of increased PA in kindergartens over the last ten years, particularly among girls. Thus, the current PA program in kindergartens effectively compensates for the decline in PA in leisure-time of weekdays of non-obese and obese preschoolers compared to 2005 and 2015. Prevalence of obesity among Czech preschool children remains relatively stable between 2005 and 2015. PMID- 27412243 TI - Prediction of 90-day mortality in older patients after discharge from an emergency department: a retrospective follow-up study. AB - BACKGROUND: Older people frequently attend the emergency department (ED) and have a high risk of poor outcome as compared to their younger counterparts. Our aim was to study routinely collected clinical parameters as predictors of 90-day mortality in older patients attending our ED. METHODS: We conducted a retrospective follow-up study at the Leiden University Medical Center (The Netherlands) among patients aged 70 years or older attending the ED in 2012. Predictors were age, gender, time and way of arrival, presenting complaint, consulting medical specialty, vital signs, pain score and laboratory testing. Cox regression analyses were performed to analyse the association between these predictors and 90-day mortality. RESULTS: Three thousand two hundred one unique patients were eligible for inclusion. Ninety-day mortality was 10.5 % for the total group. Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95 % confidence interval [95 % CI] 1.04-1.08), referral from another hospital (HR 2.74, 95 % CI 1.22-6.11), allocation to a non-surgical specialty (HR: 1.55, 95 % CI 1.13-2.14), increased respiration rate (HR up to 2.21, 95 % CI 1.25-3.92), low oxygen saturation (HR up to 1.96, 95 % CI 1.19-3.23), hypothermia (HR 2.27, 95 % CI 1.28-4.01), fever (HR 0.43, 95 % CI 0.24-0.75), high pain score (HR 1.55, 95 % CI 1.03-2.32) and the indication to perform laboratory testing (HR 3.44, 95 % CI 2.13-5.56). CONCLUSIONS: Routinely collected parameters at the ED can predict 90-day mortality in older patients presenting to the ED. This study forms the first step towards creating a new and simple screening tool to predict and improve health outcome in acutely presenting older patients. PMID- 27412244 TI - Mucilaginibacter pedocola sp. nov., isolated from a heavy-metal-contaminated paddy field. AB - Strain TBZ30T was isolated from soil of a heavy-metal-contaminated paddy field. Cells of strain TBZ30T were Gram-staining-negative, rod-shaped, non-motile and non-spore-forming. The isolate was strictly aerobic, pink-pigmented, catalase- and oxidase-positive and produced exopolysaccharides. On the basis of 16S rRNA gene phylogeny, strain TBZ30T belonged to the genus Mucilaginibacter and appeared most closely related to Mucilaginibacter gynuensis YC7003T (95.8 %), Mucilaginibacter litoreus BR-18T (95.4 %) and Mucilaginibacter mallensis MP1X4T (95.4 %). Strain TBZ30T contained menaquinone-7 as the only ubiquinone. The main cellular fatty acids included summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH), iso-C15 : 0, C16 : 0, iso-C17 : 0 3-OH and C16 : 1omega5c. The polar lipids were phosphatidylethanolamine, an unidentified phospholipid, two unidentified aminophospholipids, four unidentified aminolipids, three unidentified lipids and two unidentified glycolipids. The genomic DNA G+C content was 49.0 mol%. On the basis of polyphasic taxonomy analyses, strain TBZ30T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter pedocola sp. nov. is proposed. The type strain is TBZ30T (=KCTC 42833T=CCTCC AB 2015301T). PMID- 27412245 TI - Interleukin-1 receptor antagonist mediates toll-like receptor 3-induced inhibition of trophoblast adhesion to endometrial cells in vitro. AB - STUDY QUESTION: Is interleukin-1 receptor antagonist (IL-1RA) involved in the toll-like receptor 3 (TLR 3)-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro? SUMMARY ANSWER: IL-1RA mediates the TLR 3-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro. WHAT IS KNOWN ALREADY: It is well documented that endometrial TLR 3 activation leads to impairment of trophoblast binding to endometrial cells in vitro. IL-1RA is known as an anti-implantation factor, as its injection significantly reduced implantation rates in mice by an effect on endometrial receptivity. STUDY DESIGN, SIZE, DURATION: Poly I:C was used as a TLR3 specific ligand and endometrial cells were either treated or not with Poly I:C (treated versus control) in vitro. IL 1RA was applied to block IL-1 signal transduction. IL-1RA was knocked down by Accell Human IL1RN siRNA. Flagellin was used to stimulate TLR 5. SP600125 (JNK) was applied to inhibit the mitogen-activated protein kinases (MAPK) pathway. BAY11 -7082 was used to inhibit the nuclear factor-kappaB (NF-kappaB) pathway. The experiments were performed in three replicates on three separate days. PARTICIPANTS/MATERIALS, SETTING, METHODS: An in vitro assay was developed using RL95-2 (an endometrial cell line) and JAr (a trophoblast cell line) cells. Initially, the production of IL-1RA in RL95-2 cells in response to TLR 3 activation was measured. To determine whether the TLR 3-induced inhibition of trophoblast binding was mediated through IL-1RA: (i) we evaluated the effect of IL-1RA on the attachment of trophoblast cells to endometrial cells; (ii) we knocked down TLR3-induced IL-1RA gene expression by IL-1RA Small interfering RNA (siRNA) and evaluated trophoblast attachment to endometrial cells. Finally, to clarify through which pathway TLR 3-induced inhibition of trophoblast binding occurs: (i) activation of NF-kappaB and MAPK was detected by transfecting the cells with secreted placental alkaline phosphatase reporter plasmids bearing promoter sequences for each transcription factor; (ii) the inhibitors for NF kappaB and MAPK were used to block signaling; (iii) it was then investigated whether addition of these inhibitors could restore the TLR 3-induced impairment of trophoblast attachment to the endometrial cells. MAIN RESULTS AND THE ROLE OF CHANCE: Our results showed that addition of polyinosinic:polycytidylic acid (Poly I:C) to RL95-2 cells significantly increased the production of IL-1RA (P < 0.05). Addition of human recombinant IL-1RA to RL95-2 cells remarkably decreased the adhesion rate of trophoblast cells to endometrial cells (P < 0.05). In addition, suppression of TLR3-induced IL-1RA gene expression in RL95-2 cells significantly restored trophoblast cells attachment to endometrial cells in the presence of Poly I:C (P < 0.05). Only TLR3 and not TLR5 induced MAPK activation (P < 0.05). TLR3 ligation did not affect NF-kappaB activation. Of NF-kB and MAPK inhibitors, only MAPK's inhibitor could achieve restoration of spheroid adhesion to endometrial cells (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This study has been only done in vitro. Future in vivo studies will confirm our data. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study have a potential clinical application in introducing IL-1RA as one of the diagnostic infertility markers in the endometrium, which can affect the process of embryo adhesion at the time of implantation. Moreover, based on the novel data obtained in the current study, blocking and regulating the MAPK pathway by its inhibitors can be used as a new strategy to prevent and treat virus-induced infertility cases in ART techniques. STUDY FUNDING/COMPETING INTEREST: This study was partially funded by a Marie Curie IIF-253948 grant to I.C. and was partially funded by the author's institutions. The authors have no conflict of interest to declare. PMID- 27412246 TI - Dienogest mediates midkine suppression in endometriosis. AB - STUDY QUESTION: What are the effects of dienogest (DNG) on midkine (MK) production in women with endometriosis? SUMMARY ANSWER: DNG-mediated down regulation of MK in vivo and in vitro. WHAT IS KNOWN ALREADY: DNG is an oral progestin that alleviates painful symptoms of women with endometriosis with a favourable tolerability and safety profile. Its effects on MK, a growth factor that plays an important role in endometriosis, have not yet been investigated. STUDY DESIGN, SIZE, DURATION: Prospective in vivo study on 283 patients subjected to laparoscopy for benign pathologies in a University hospital and in vitro cultures of primary endometrial stromal cells (ESC) from 6 of these women with histologically confirmed endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: MK concentrations in the peritoneal fluid (PF) of women were measured by ELISA and compared based on endometriosis status and the use of DNG. A subsequent in vitro analysis with ESC was used to confirm the direct influence of DNG and other progestins including, norethisterone acetate (NETA) and medroxyprogesterone acetate (MPA) on MK mRNA production. MAIN RESULTS AND THE ROLE OF CHANCE: The final study population consisted of 253 women. Of these, 165 suffered from endometriosis, with 62 of them taking DNG (DNG group) and 103 taking no hormone treatment (non-DNG group) during at least 3 months before surgery. Another 88 women were endometriosis free (non-endometriosis group). The concentration of MK was highest in the PF of women in the non-DNG group (median 5.26 ng/ml, IQR 2.74 8.46). Significantly lower concentrations were found in the non-endometriosis group (median 3.51 ng/ml, IQR: 1.90-7.53, P = 0.028). The lowest concentrations were found in the DNG group (median 2.44 ng/ml, IQR: 1.12-4.70, P < 0.0001 versus non-DNG group, P = 0.048 versus non-endometriosis group). The treatment of primary cultured ESC with DNG (10(-5) M) suppressed MK mRNA production (P = 0.016), whereas MPA (P = 0.109) and NETA (P = 0.422) at same concentrations did not show a similar effect. LIMITATIONS, REASONS FOR CAUTION: The non-randomized design of the study. WIDER IMPLICATIONS OF THE FINDINGS: These findings could indicate a direct effect of DNG on endometriotic cells that could contribute to its effectiveness in the treatment of this disease. STUDY FUNDING/COMPETING INTERESTS: Funding was received from Swiss National Science Foundation (Grant No. 320030_140774). M.D.M. has received fees for speaking at scientific meetings from Bayer. The other authors have no conflicts of interest to declare.The authors state that the manufacturer of dienogest has in no way influenced the performance or outcomes of this study. PMID- 27412247 TI - Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome. AB - STUDY QUESTION: Should fertility preservation be offered to children with Klinefelter syndrome (KS)? SUMMARY ANSWER: Current evidence shows that fertility preservation should not be offered to adolescents with KS younger than 16 years because of lower retrieval rates for germ cells by testicular sperm extraction (TESE) compared with retrieval rates for adolescents and adults between 16 and 30 years. WHAT IS KNOWN ALREADY: KS, the most common chromosomal disorder in men leading to non-obstructive azoospermia, is caused by the presence of at least one additional X chromosome. The onset of puberty in adolescents with KS leads to progressive degeneration of the testicular environment. The impact of the subsequent tissue degeneration on fertility potential of patients with KS is unknown, but in previous literature it has been suggested that fertility preservation should be started in adolescents as early as possible. However spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. This review discusses the current evidence for fertility preservation in children and adolescents and possible prognostic markers for fertility treatment in KS. STUDY DESIGN, SIZE, DURATION: An extensive literature search was conducted, searching Pubmed, Embase, Cinahl and Web of Science from origin until April 2016 for 'Klinefelter syndrome' and 'fertility' and various synonyms. Titles and abstracts have been scanned manually by the authors for eligibility. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 76 studies were found to be eligible for inclusion in this review. Information from the papers was extracted separately by two authors. MAIN RESULTS AND THE ROLE OF CHANCE: Various studies have shown that pre-pubertal children with KS already have a reduced number of germ cells despite a normal hormonal profile during childhood. The presence of spermatozoa in the ejaculate of adolescents with KS is extremely rare. Using TESE, the retrieval rates of spermatozoa for adolescents younger than 16 years old are much lower (0-20%) compared with those for adolescents and young adults between 16 and 30 years old (40-70%). Although spermatogonia can be found by TESE in about half of the peri-pubertal adolescents, there are currently no clinically functional techniques for their future use. Children and adolescents need to be informed that early fertility preservation before the age of 16 cannot guarantee fertility later in life and may even reduce the chances for offspring by removing functional immature germ cells which may possibly develop into spermatozoa after puberty. Furthermore, except for the age of patients with KS, there are no identified factors that can reliably be used as a predictive marker for fertility preservation. LIMITATIONS, REASONS FOR CAUTION: Most of the evidence presented in this review is based on studies including a small number of adolescents with KS. Therefore, the studies may have been underpowered to detect clinically significant differences for their various outcomes, especially for potential predictive factors for fertility preservation, such as hormone levels. Furthermore, the population of patients with KS diagnosed during childhood might be different from the adult population with KS where the diagnosis is based on infertility. Results based on comparisons between the two groups must be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limitations, this review summarizes the current evidence for managing fertility preservation in patients with KS to provide optimal health care. STUDY FUNDING/COMPETING INTERESTS: There was no funding for this study. S.F., Y.H., K.D., W.L.M.N., D.S., H.L.C.-v.d.G. and L.R. declare to have no conflicts of interests. D.D.M.B. reports grants from Merck Serono, grants from Ferring and grants from MSD, outside the submitted work. K.F. reports personal fees from MSD (commercial sponsor), personal fees from Ferring (commercial sponsor), grants from Merck-Serono (commercial sponsor), grants from Ferring (commercial sponsor) and grants from MSD (commercial sponsor), outside the submitted work. PMID- 27412248 TI - Urinary paracetamol and time-to-pregnancy. AB - STUDY QUESTION: Is preconception urinary paracetamol (acetaminophen) associated with time-to-pregnancy (TTP)? SUMMARY ANSWER: Higher urinary paracetamol concentrations among male partners were associated with a longer TTP. WHAT IS KNOWN ALREADY: Paracetamol is a commonly used analgesic among women and men of all ages. As metabolites of select chemicals used in the manufacturing of polyurethane foam, dyes and various industrial products, as well as a common medicinal product, paracetamol and its primary metabolite p-aminophenol, are ubiquitous in the environment. Studies investigating the relationship between adult urinary concentrations of paracetamol and TTP are lacking. STUDY DESIGN, SIZE, DURATION: This prospective cohort included 501 couples discontinuing contraception for the purposes of attempting conception during the years 2005 2009 and residing in Michigan or Texas, USA. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total urinary paracetamol, its metabolite para-aminophenol (p aminophenol), and a summary measure of both urinary biomarkers were quantified by ultra-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry (UPLC-ESI-MS/MS). Female partners used the Clearblue(r) digital home test to confirm pregnancy. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs), adjusting for age, body mass index (BMI), urinary creatinine, preconception smoking status, race/ethnicity and household income. Models were further adjusted for hypothyroidism and hypertension as an attempt to account for possible indications of paracetamol medication use. FOR estimates <1.0 denote a longer TTP (diminished fecundity). Models were performed to examine urinary concentrations of paracetamol as a continuous and variable or categorized into quartiles. In light of TTP being a couple-dependent outcome, models were first performed for females and males, modeled separately, and then modeled for couples with each partner's concentrations being adjusted for the other. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 501 enrolled couples, 347 (69%) had an human chorionic gonadotrophin confirmed pregnancy. Urinary concentrations of paracetamol were lowest among females and males who achieved pregnancy and p-aminophenol concentrations were lowest among those not achieving pregnancy. Urinary paracetamol concentrations were higher among female than male partners (Median = 26.6 and 13.2 ng/ml, respectively; P < 0.0001). After adjustment for age, BMI, urinary creatinine, preconception smoking status, race/ethnicity and household income, the highest quartile of male urinary paracetamol was associated with a longer TTP [FOR = 0.67; 95% CI = (0.47, 0.95)]. This association remained after adjustment for chronic health conditions, hypothyroidism and hypertension and female partner's urinary paracetamol concentration [FOR = 0.65; 95% CI = (0.45, 0.94)]. No associations were observed between female or male partners' urinary concentrations of paracetamol or of its metabolite p-aminophenol when urinary concentrations were modeled continuously. LIMITATIONS, REASONS FOR CAUTION: Only a single spot urine was available for analysis despite the short-lived nature of paracetamol. Additionally, participants were not asked to provide information on indication of use for paracetamol medications; any underlying conditions for the paracetamol use would have been potential confounders. WIDER IMPLICATIONS OF THE FINDINGS: If corroborated with more robust studies, findings from our exploratory analysis may have both clinical and public health relevance among reproductive aged individuals, including those trying for pregnancy, given the prevalent use of paracetamol/acetaminophen medications and the ubiquitous nature of paracetamol in the environment. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Institutes of Health, Intramural Research Program, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358; HHSN27500001/HHSN27500001). None of the authors have any conflicts to declare. PMID- 27412249 TI - Young women's psychological distress after a diagnosis of polycystic ovary syndrome or endometriosis. AB - STUDY QUESTION: Do young women with polycystic ovary syndrome (PCOS) or endometriosis report more psychological distress than their peers without a history of these conditions? SUMMARY ANSWER: Young women (aged 18-23 years) with PCOS or endometriosis had a greater risk of moderate to severe psychological distress than women without a history of these conditions. WHAT IS KNOWN ALREADY: Psychological distress appears common among women with PCOS and endometriosis. However, population-based studies that examine the psychological outcomes for adolescents and young women are generally absent from the literature. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of data collected from 17 015 young, Australian women participating in a national, longitudinal cohort study. Women were first surveyed in 2012-2013 when they were aged 18-23 years. In 2014, women completed the second survey when they were aged 19-24 years and 11324 (67%) women responded. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed data from 11 238 women who participated in both Surveys 1 and 2 and who responded to questions about PCOS and endometriosis. Using logistic regression, we compared the odds of moderate to severe psychological distress at Surveys 1 and 2 for women reporting a recent diagnosis (within the last 12 months) of PCOS or endometriosis and women with a pre-existing diagnosis, with that for women without a history of these conditions. MAIN RESULTS AND THE ROLE OF CHANCE: At Survey 2, around 60% of women reporting a diagnosis of PCOS or endometriosis had moderate to severe levels of psychological distress. Compared to women without a history of these conditions, the odds of moderate to severe psychological distress at Survey 2 were significantly higher for women recently diagnosed with PCOS [Adjusted Odds Ratio (AOR) = 1.62, 95% CI = 1.21-2.18] or endometriosis (AOR= 1.77; 95% CI = 1.20-2.63) and for women with a pre-existing diagnosis of PCOS (AOR = 1.57, 95% CI = 1.30-1.89) or endometriosis (AOR = 1.61; 95% CI = 1.26 2.06). Women recently diagnosed with PCOS or endometriosis also had a greater likelihood of moderate to severe distress in the year prior to their diagnosis. The association between PCOS and psychological distress was attenuated when adjusting for BMI, but hormonal contraceptive use did not attenuate the risk of distress among the women with PCOS or endometriosis. LIMITATIONS, REASONS FOR CAUTION: All data were self-reported and, therefore, the diagnoses of PCOS or endometriosis were not confirmed by a medical practitioner. WIDER IMPLICATIONS OF THE FINDINGS: Health professionals should be aware of the potential psychosocial and healthcare needs among young women with these conditions, particularly women with PCOS who are obese. While hormonal contraceptives may help to regulate the hormonal aspects of these conditions, they do not appear to reduce women's psychological distress. Because psychological distress among the young women in this study remained elevated even after diagnosis, this supports the need for multidisciplinary health care to help women adjust to their diagnosis and treatment regimens and facilitate positive, long-term mental health outcomes. Future research that examines medical and psychosocial sources of distress for young women with PCOS and endometriosis is needed. STUDY FUNDING/COMPETING INTERESTS: I.J.R. was supported by an Australian National Health and Medical Research Council Centre for Research Excellence (grant number: APP1000986). G.D.M. is funded by the Australian Research Council Future Fellowship (FT120100812). The Australian Longitudinal Study on Women's Health is funded by the Australian Government Department of Health. H.T. is supported by an Australian National Health and Medical Research Council Practitioner Fellowship. The authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: N/A. PMID- 27412250 TI - Targeting insulin-producing beta cells for regenerative therapy. AB - Pancreatic beta cells differ in terms of glucose responsiveness, insulin secretion and proliferative capacity; however, the molecular pathways that regulate this cellular heterogeneity are unknown. We have identified the Wnt planar cell polarity (PCP) effector Flattop (FLTP) as a biomarker that identifies mature beta cells in the islets of Langerhans. Interestingly, three-dimensional architecture and Wnt-PCP ligands are sufficient to trigger mouse and human beta cell maturation. These results highlight the fact that novel biomarkers shed light on the long-standing mystery of beta cell heterogeneity and identify the Wnt-PCP pathway as triggering beta cell maturation. Understanding heterogeneity in the islets of Langerhans might allow targeting of beta cell subpopulations for regenerative therapy and provide building principles for stem cell-derived islets. This review summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Harry Heimberg and colleagues, DOI: 10.1007/s00125-016-3879-6 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ). PMID- 27412251 TI - Competition Between Biosimilars and Patented Biologics: Learning from European and Japanese Experience. AB - BACKGROUND: The expiry of patents for costly biologics is creating new momentum on the pharmaceutical market for biosimilars (copies of off-patent biologics) and paving the way for their development. However, little is known about the competitiveness of biosimilars versus their originators and other biologics belonging to the same therapeutic class. OBJECTIVE: The main goal of this study was to analyse the type of competition generated by the first biosimilars commercialised on key global biologic markets and to grasp their economic model. The secondary goal was to distinguish the main factors likely to influence the uptake of biosimilars on national markets. METHODS: To be included in this study, countries had to meet three conditions: the regulatory framework for the development of biosimilars closely resembled that in Europe, biosimilars were marketed in 2014, and the value of the biologics market was >US$3 billion. We analysed granulocyte colony-stimulating factors (GCSFs) and erythropoietins (EPOs) over the period 2007-2014 because these are the two main therapeutic classes that have been 'biosimilarised' and thus have many years of experience available. We assessed market sizes, retail/hospital distribution mixes, incentives for using biosimilars and price discounts for originators versus biosimilars. We conducted a linear regression analysis to assess the relationship between uptakes of biosimilars and the market shares of other biologics. RESULTS: The EU-5 (France, Germany, Italy, Spain and the UK) and Japanese GCSF and EPO markets are highly-country-specific. Uptake of biosimilars seems to depend on retail/hospital distribution mixes and on medical practice. Depending on the therapeutic class and the market sector (retail or hospital), biosimilars may compete with first-generation or second-generation products or both. Some incentives implemented to encourage the use of biosimilars had mixed results. Overall, discounts for biosimilars versus originators are not factors that determine global uptake of biosimilars. CONCLUSION: Unlike generics, there appears to be no unique economic model for biosimilars. Moreover, a new phenomenon occurs with biosimilars: sometimes, they are able to take market shares from subsequent generations of biologics. PMID- 27412253 TI - An interdisciplinary approach to study individuality in biological and physical systems functioning. AB - Signals of system functioning of different nature are presented in the parameter space (state-velocity-acceleration) as a trajectory of dynamic events. Such signals geometrization allows to reveal the hidden spatio-temporal correlation in dynamics of systems functioning. It is shown that the nature of relationship between the dynamic parameters of signal determines the natural cycle of sensor functioning. Its restructuring displays the inherited features of systems functioning in signature package. The universal differential-geometry parameters and new integrative indexes of system functioning are used to analyze the signatures of biological and physical signals. PMID- 27412252 TI - Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease. AB - BACKGROUND: Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome. METHODS: We performed a prospective cohort study of 19 treatment-naive pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples. RESULTS: Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status. CONCLUSIONS: Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment. PMID- 27412254 TI - Atypical enteropathogenic Escherichia coli as aetiologic agents of sporadic and outbreak-associated diarrhoea in Brazil. AB - Enteropathogenic Escherichia coli (EPEC) are important agents of diarrhoea in industrialized as well as developing countries, such as Brazil. The hallmark of EPEC pathogenesis is the establishment of attaching and effacing lesions in enterocytes, in which pedestal-like structures are formed underneath adherent bacteria. EPEC are divided into two subgroups, typical (tEPEC) and atypical (aEPEC), based on the presence of the EPEC adherence factor plasmid in tEPEC and its absence in aEPEC. This study was designed to characterize 82 aEPEC isolates obtained from stool samples of diarrhoeic patients during 2012 and 2013 in Brazil. The majority of the aEPEC were assigned to the phylo-group B1 (48.8 %), and intimin subtypes theta (20.7 %), beta1 (9.7 %) and lambda (9.7 %) were the most prevalent among the isolates. The nleB and nleE genes were concomitantly detected in 32.9 % of the isolates, demonstrating the occurrence of the pathogenicity island O122 among them. The O157-plasmid genes (ehxA and/or espP) were detected in 7.3 % of the isolates, suggesting that some aEPEC could be derived from Shiga-toxin-producing E. coli that lost the stx genes while trafficking in the host. PFGE of 14 aEPEC of serotypes O2 : H16, O33 : H34, O39 : H9, O108 : H- and ONT : H19 isolated from five distinct outbreaks showed serotype specific PFGE clusters, indicating a high degree of similarity among the isolates from the same event, thus highlighting these serotypes as potential aetiologic agents of diarrhoeal outbreaks in Brazil. PMID- 27412256 TI - MoS2 /WS2 -Graphene Composites through Thermal Decomposition of Tetrathiomolybdate/Tetrathiotungstate for Proton/Oxygen Electroreduction. AB - MoS2 and WS2 have been prepared on a conductive graphene support by thermal reduction of tetrathiotungstate/tetrathiomolybdate and graphite oxide. Whereas the catalytic properties towards hydrogen evolution are strongly influenced by the Magneli phases formed as a byproduct during the synthesis, the catalytic activity towards oxygen reduction of these composite materials is not affected by this phenomenon and these materials exhibit high catalytic activity towards this industrially important reaction. PMID- 27412255 TI - Appraisal of clinical practice guidelines for management of paediatric type 2 diabetes mellitus using the AGREE II instrument: a systematic review protocol. AB - BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents is increasing. This has spurred the development and publication of clinical practice guidelines (CPGs) for the management of paediatric T2DM. Given the long-term complications of T2DM, optimal management is important to prevent or delay these complications. However, the quality of published CPGs has not yet been empirically evaluated. Our objective is to systematically appraise all published CPGs for the management of T2DM in children and adolescents. METHODS: We will identify all published CPGs that address T2DM in children and adolescents through MEDLINE, Embase, CINAHL, Trip, and the National Guideline Clearinghouse and will screen diabetes and paediatric societies and associations' websites. Search records will be screened in duplicate for inclusion. Grey literature will be covered by systematically searching publications of all relevant diabetes societies and associations and other health organizations for CPGs that meet our inclusion criteria. CPGs deemed eligible for inclusion will be retrieved. Quality assessment will be conducted using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool by a team of four appraisers. Scaled scores of the AGREE II will be used to gauge the overall quality of CPGs. DISCUSSION: The results of this review will be disseminated through presentations at local, national, and international conferences and publication in a peer-reviewed journal. The results of this review can help improve the reporting of future guidelines, inform decisions of policy-makers to endorse CPGs, and affect the choice of guideline use in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016034187. PMID- 27412257 TI - Measuring the quality of life of people at the end of life: The McGill Quality of Life Questionnaire-Revised. AB - BACKGROUND: The McGill Quality of Life Questionnaire has been widely used with people with life-threatening illnesses without modification since its publication in 1996. With use, areas for improvement have emerged; therefore, various minor modifications were tested over time. AIM: To revise the McGill Quality of Life Questionnaire (McGill Quality of Life Questionnaire-Revised) while maintaining or improving its psychometric properties and length, keeping it as close as possible to the McGill Quality of Life Questionnaire to enable reasonable comparison with existing McGill Quality of Life Questionnaire literature. DESIGN: Data sets from eight studies were used (four studies originally used to develop the McGill Quality of Life Questionnaire, two to develop new McGill Quality of Life Questionnaire versions, and two with unrelated purposes). The McGill Quality of Life Questionnaire-Revised was developed using analyses of measurement invariance, confirmatory factor analysis, and calculation of correlations with the McGill Quality of Life Questionnaire's global quality of life item. SETTING/PARTICIPANTS: Data were from 1702 people with life-threatening illnesses recruited from acute and palliative care units, palliative home care services, and oncology and HIV/AIDS outpatient clinics. RESULTS: The McGill Quality of Life Questionnaire-Revised consists of 14 items (plus the global quality of life item). A new Physical subscale was created combining physical symptoms and physical well-being and a new item on physical functioning. The Existential subscale was reduced to four items. The revised Support subscale, renamed Social, focuses more on relationships. The Psychological subscale remains unchanged. Confirmatory factor analysis results provide support for the measurement structure of the McGill Quality of Life Questionnaire-Revised. The overall scale has good internal consistency reliability ( alpha = 0.94). CONCLUSION: The McGill Quality of Life Questionnaire-Revised improves on and can replace the McGill Quality of Life Questionnaire since it contains improved wording, a somewhat expanded repertoire of concepts with fewer items, and a single subscale for the physical domain, while retaining good psychometric properties. PMID- 27412258 TI - Adding items that assess changes in activities of daily living does not improve the predictive accuracy of the Palliative Prognostic Index. AB - BACKGROUND: Changes in activities of daily living in cancer patients may predict their survival. The Palliative Prognostic Index is a useful tool to evaluate cancer patients, and adding an item about activities of daily living changes might improve its predictive value. AIM: To clarify whether adding an item about activities of daily living changes improves the accuracy of Palliative Prognostic Index. DESIGN: Multicenter prospective cohort study. SETTING: A total of 58 palliative care services in Japan. PARTICIPANTS: Patients aged >20 years diagnosed with locally extensive or metastatic cancer (including hematological neoplasms) who had been admitted to palliative care units, were receiving care by hospital-based palliative care teams, or were receiving home-based palliative care. Palliative care physicians recorded clinical variables at the first assessment and followed up patients 6 months later. RESULTS: A total of 2425 subjects were recruited and 2343 of these had analyzable data. The C-statistic of the original Palliative Prognostic Index was 0.801, and those of modified Palliative Prognostic Indices ranged from 0.793 to 0.805 at 3 weeks. For 6-week survival predictions, the C-statistic of the original Palliative Prognostic Index was 0.802, and those of modified Palliative Prognostic Indices ranged from 0.791 to 0.799. The weighted kappa of the original Palliative Prognostic Index was 0.510, and those of modified Palliative Prognostic Indices ranged from 0.484 to 0.508. CONCLUSION: Adding items about activities of daily living changes to the Palliative Prognostic Index did not improve prognostic value in advanced cancer patients. PMID- 27412259 TI - A novel covalent approach to bio-conjugate silver coated single walled carbon nanotubes with antimicrobial peptide. AB - BACKGROUND: Due to increasing antibiotic resistance, the use of silver coated single walled carbon nanotubes (SWCNTs-Ag) and antimicrobial peptides (APs) is becoming popular due to their antimicrobial properties against a wide range of pathogens. However, stability against various conditions and toxicity in human cells are some of the major drawbacks of APs and SWCNTs-Ag, respectively. Therefore, we hypothesized that APs-functionalized SWCNTs-Ag could act synergistically. Various covalent functionalization protocols described previously involve harsh treatment of carbon nanotubes for carboxylation (first step in covalent functionalization) and the non-covalently functionalized SWCNTs are not satisfactory. METHODS: The present study is the first report wherein SWCNTs-Ag were first carboxylated using Tri sodium citrate (TSC) at 37 degrees C and then subsequently functionalized covalently with an effective antimicrobial peptide from Therapeutic Inc., TP359 (FSWCNTs-Ag). SWCNTs-Ag were also non covalently functionalized with TP359 by simple mixing (SWCNTs-Ag-M) and both, the FSWCNTs-Ag (covalent) and SWCNTs-Ag-M (non-covalent), were characterized by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet visualization (UV VIS) and transmission electron microscopy (TEM). Further the antibacterial activity of both and TP359 were investigated against two gram positive (Staphylococcus aureus and Streptococcus pyogenes) and two gram negative (Salmonella enterica serovar Typhimurium and Escherichia coli) pathogens and the cellular toxicity of TP359 and FSWCNTs-Ag was compared with plain SWCNTs-Ag using murine macrophages and lung carcinoma cells. RESULTS: FT-IR analysis revealed that treatment with TSC successfully resulted in carboxylation of SWCNTs-Ag and the peptide was indeed attached to the SWCNTs-Ag evidenced by TEM images. More importantly, the present study results further showed that the minimum inhibitory concentration (MIC) of FSWCNTs-Ag were much lower (~7.8-3.9 ug/ml with IC50: ~4-5 ug/ml) compared to SWCNTs-Ag-M and plain SWCNTs-Ag (both 62.6 ug/ml, IC50: ~31-35 ug/ml), suggesting that the covalent conjugation of TP359 with SWCNTs-Ag was very effective on their counterparts. Additionally, FSWCNTs-Ag are non-toxic to the eukaryotic cells at their MIC concentrations (5-2.5 ug/ml) compared to SWCNTs-Ag (62.5 ug/ml). CONCLUSION: In conclusion, we demonstrated that covalent functionalization of SWCNTs-Ag and TP359 exhibited an additive antibacterial activity. This study described a novel approach to prepare SWCNT-Ag bio conjugates without loss of antimicrobial activity and reduced toxicity, and this strategy will aid in the development of novel and biologically important nanomaterials. PMID- 27412261 TI - Troponin structure: its modulation by Ca(2+) and phosphorylation studied by molecular dynamics simulations. AB - The only available crystal structure of the human cardiac troponin molecule (cTn) in the Ca(2+) activated state does not include crucial segments, including the N terminus of the cTn inhibitory subunit (cTnI). We have applied all-atom molecular dynamics (MD) simulations to study the structure and dynamics of cTn, both in the unphosphorylated and bis-phosphorylated states at Ser23/Ser24 of cTnI. We performed multiple microsecond MD simulations of wild type (WT) cTn (6, 5 MUs) and bisphosphorylated (SP23/SP24) cTn (9 MUs) on a 419 amino acid cTn model containing human sequence cTnC (1-161), cTnI (1-171) and cTnT (212-298), including residues not present in the crystal structure. We have compared our results to previous computational studies, and proven that longer simulations and a water box of at least 25 A are needed to sample the interesting conformational shifts both in the native and bis-phosphorylated states. As a consequence of the introduction into the model of the C-terminus of cTnT that was missing in previous studies, cTnC-cTnI interactions that are responsible for the cTn dynamics are altered. We have also shown that phosphorylation does not increase cTn fluctuations, and its effects on the protein-protein interaction profiles cannot be assessed in a significant way. Finally, we propose that phosphorylation could provoke a loss of Ca(2+) by stabilizing out-of-coordination distances of the cTnC's EF hand II residues, and in particular Ser 69. PMID- 27412260 TI - The Role of Group II Metabotropic Glutamate Receptors in the Striatum in Electroacupuncture Treatment of Parkinsonian Rats. AB - AIMS: Glutamatergic transmission may play a critical role in the pathogenesis of Parkinson's disease (PD). Electroacupuncture (EA) has been demonstrated to effectively alleviate PD symptoms. In this study, a potential glutamate-dependent mechanism underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on motor behaviors, dopamine contents, glutamate release, and group II metabotropic glutamate receptor (mGluR2/3) expression in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were examined. RESULTS: Unilateral 6-OHDA lesions of the nigrostriatal system caused a marked increase in glutamate content in the ipsilateral cortex and striatum. mGluR2/3 protein expression and mGluR3 mRNA expression were reduced in the striatum. Noticeably, prolonged EA stimulation at 100 Hz significantly reversed these changes in the striatal glutamate system. Behaviorally, EA improved the motor deficits induced by 6-OHDA lesions. Intrastriatal infusion of an mGluR2/3 antagonist APICA blocked the improving effect of EA. CONCLUSIONS: These data collectively demonstrate that the group II mGluR-mediated glutamatergic transmission in the striatum is sensitive to dopamine depletion and may serve as a substrate of EA for mediating the therapeutic effect of EA in a rat model of PD. PMID- 27412262 TI - The Need for Early Detection and Treatment in Alzheimer's Disease. PMID- 27412263 TI - TP53 mutations on circulating cell-free DNA. PMID- 27412264 TI - Score Predicting Acute Chest Syndrome During Vaso-occlusive Crises in Adult Sickle-cell Disease Patients. AB - BACKGROUND: Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' Emergency-Room admissions and hospitalizations. Acute chest syndrome (ACS), a life-threatening complication, can occur during VOC, be fatal and prolong hospitalization. No predictive factor identifies VOC patients who will develop secondary ACS. METHODS: This prospective, monocenter, observational study on SS/S-beta0thalassemia SCD adults aimed to identify parameters predicting ACS at Emergency-Department arrival. The primary endpoint was ACS onset within 15days of admission. Secondary endpoints were hospitalization duration, morphine consumption, pain evaluation, blood transfusion(s) (BT(s)), requiring intensive care and mortality. FINDINGS: Among 250 VOCs included, 247 were analyzed. Forty-four (17.8%) ACSs occurred within 15 (median [IQR] 3 [2, 3]) days post-admission based on auscultation abnormalities; missing chest radiographs excluded three patients. Comparing ACS to VOC, respectively, median hospital stay was longer 9 [7-11] vs 4 [3-7] days (p<0.0001), 7/41 (17%) vs 1/203 (0.5%) required intensive care (p<0.0001), and 20/41 (48.7%) vs 6/203 (3%) required BTs (p<0.0001). No patient died. The multivariate model retained reticulocyte and leukocyte counts, and spine and/or pelvis pain as being independently associated with ACS; the resulting ACS predictive score's area under the ROC was 0.840 [95% CI 0.780-0.900], 98.8% negative-predictive value and 39.5% positive-predictive value for the real ACS incidence. INTERPRETATION: The ACS-predictive score is simple, easily applied and could change VOC management and therapeutic perspectives. Assessed ACS risk could lead to earlier discharges or close monitoring and rapid medical intensification to prevent ACS. PMID- 27412265 TI - Introducing the Wiley Transplant Peer Review Network. PMID- 27412266 TI - The labial gene is required to terminate proliferation of identified neuroblasts in postembryonic development of the Drosophila brain. PMID- 27412267 TI - Quasi-steady state aerodynamics of the cheetah tail. AB - During high-speed pursuit of prey, the cheetah (Acinonyx jubatus) has been observed to swing its tail while manoeuvring (e.g. turning or braking) but the effect of these complex motions is not well understood. This study demonstrates the potential of the cheetah's long, furry tail to impart torques and forces on the body as a result of aerodynamic effects, in addition to the well-known inertial effects. The first-order aerodynamic forces on the tail are quantified through wind tunnel testing and it is observed that the fur nearly doubles the effective frontal area of the tail without much mass penalty. Simple dynamic models provide insight into manoeuvrability via simulation of pitch, roll and yaw tail motion primitives. The inertial and quasi-steady state aerodynamic effects of tail actuation are quantified and compared by calculating the angular impulse imparted onto the cheetah's body and its shown aerodynamic effects contribute to the tail's angular impulse, especially at the highest forward velocities. PMID- 27412268 TI - Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first-line therapy for triple-negative, metastatic, or locally advanced breast cancer: Results from the GINECO A-TaXel phase 2 study. AB - BACKGROUND: The current study was performed to determine the efficacy and safety of first-line combination therapy with bevacizumab, paclitaxel, and capecitabine for triple-negative, locally advanced/metastatic breast cancer (LA/MBC). METHODS: Patients with measurable triple-negative LA/MBC who had received no prior chemotherapy for their disease received 4-weekly cycles of paclitaxel (80 mg/m2 on days 1, 8, and 15 for up to 6 cycles) combined with capecitabine (800 mg/m2 twice daily on days 1-5, 8-12, and 15-19) and bevacizumab (10 mg/kg on days 1 and 14) repeated every 4 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was the objective response rate; secondary endpoints were progression-free survival, duration of response, overall survival, and safety. RESULTS: Between April 2010 and March 2012, 62 eligible patients were enrolled. The median age of the patients was 57 years, 74% had received adjuvant chemotherapy, and 65% had visceral metastases. Patients received a median of 6 cycles (range, 1-45 cycles). The objective response rate was 77% (95% confidence interval [95% CI] 66%-88%), including complete response in 19% of patients. The median duration of response was 5.6 months (range, 1.3-27.6 months). The median progression-free survival was 7.6 months (95% CI, 6.3-9.0 months) and the median overall survival was 19.2 months (95% CI, 17.4-20.9 months). The most common grade >=3 adverse events were hypertension (35% of patients) and neutropenia (23% of patients); 5% of patients experienced febrile neutropenia. Grade >=2 hand-foot syndrome, alopecia, and nail toxicity each occurred in 40% of patients (adverse events were recorded before every cycle and graded according to Common Terminology Criteria for Adverse Events [version 4.0]). Treatment was interrupted because of toxicity in 22% of patients. CONCLUSIONS: A triplet regimen of paclitaxel, capecitabine, and bevacizumab followed by maintenance therapy with capecitabine and bevacizumab demonstrated high activity and manageable safety in this difficult-to-treat population. Cancer 2016;122:3119-26. (c) 2016 American Cancer Society. PMID- 27412269 TI - Tubaramure, a Food-Assisted Integrated Health and Nutrition Program in Burundi, Increases Maternal and Child Hemoglobin Concentrations and Reduces Anemia: A Theory-Based Cluster-Randomized Controlled Intervention Trial. AB - BACKGROUND: Despite their popularity, food-assisted maternal and child health and nutrition (MCHN) programs have not been evaluated rigorously, and evidence of their impacts on maternal and child outcomes is scant. OBJECTIVE: This study estimated the impact of Tubaramure, a food-assisted MCHN program implemented by Catholic Relief Services and partners in eastern Burundi, on hemoglobin and anemia (primary outcome) in children aged 0-23.9 mo and their mothers and explored the impact pathways. The program targeted women and their children during their first 1000 d of life and included 1) food rations, 2) strengthening and promotion of the use of health services, and 3) behavior change communication. METHODS: This was a cluster-randomized controlled study to assess program impact by using cluster fixed-effects double-difference models with repeated cross-sectional data (baseline and follow-up 2 y later). We explored impact pathways by estimating impact on intermediary factors addressed by Tubaramure that are known determinants of hemoglobin and anemia and by regressing hemoglobin and anemia on each determinant to assess the plausibility that the effect operated through each determinant. RESULTS: Hemoglobin decreased and anemia increased markedly from baseline to follow-up, but Tubaramure had a significant (P < 0.05) beneficial effect on both children [6.1 percentage points (pps)] and mothers who had given birth in the previous 3 mo (34.9 pps). The program also had significant (P < 0.05) impacts on factors along the hypothesized impact pathways: dietary diversity, consumption of iron-rich foods, morbidity, and fever for child hemoglobin and dietary diversity, consumption of iron-rich foods, and current bed-net use for maternal anemia. CONCLUSIONS: We showed, for the first time to our knowledge, that a food-assisted MCHN program had a positive impact on anemia and hemoglobin in both mothers and children. The plausible pathways identified highlight the importance of addressing multiple determinants of anemia. This trial was registered at clinicaltrials.gov as NCT01072279. PMID- 27412270 TI - Health-related quality-of-life questionnaire for women with polycystic ovary syndrome: a Chinese translation and validation study. AB - OBJECTIVE: To evaluate the reliability, validity, and responsiveness of the Chinese version of the polycystic ovary syndrome questionnaire (PCOSQ). DESIGN: Translation and validation study. SETTING: Gynaecology clinic and paediatric adolescent gynaecology clinic at the study institute. POPULATION: Chinese women, 16 years of age or older, with polycystic ovary syndrome (PCOS). METHODS: Women completed the Chinese version of the PCOSQ and the Short-Form Health Survey (SF 36). Their sociodemographic details, clinical parameters, and biochemical results were recorded. A subset of 50 women repeated the PCOSQ 1 week later to evaluate test-retest reliability. Women subsequently received treatment for the symptoms of PCOS. Six months later, 100 women completed the PCOSQ and clinical parameters were assessed to evaluate the responsiveness of the PCOSQ. MAIN OUTCOME MEASURES: Internal reliability, test-retest reliability, convergent validity, criterion validity, and responsiveness. RESULTS: A total of 262 Chinese women completed the study. Values of Cronbach's alpha coefficient were all above 0.7, demonstrating a good standard of internal consistency in all subscales. For the test-retest reliability, intraclass correlation coefficients showed excellent stability among the subscales (range 0.82-0.92, P < 0.001). Convergent validity was demonstrated by positive correlations with the subscales of SF-36 and clinical parameters like body mass index (BMI), waist-hip ratio (WHR), hirsutism score, menstrual regularity, and infertility, and the respective subscales. Improvement in PCOSQ scores was seen in women with improvements in BMI and menstrual patterns; however, these findings did not reach statistical significance. CONCLUSIONS: The Chinese version of PCOSQ is reliable and valid for use in women with PCOS. TWEETABLE ABSTRACT: The Chinese version of the PCOSQ is reliable and valid for use. PMID- 27412272 TI - ESPR postmortem imaging task force: where we begin. AB - A new task force on postmortem imaging was established at the annual meeting of the European Society of Paediatric Radiology (ESPR) in Graz, Austria, in 2015. The postmortem task force is separate from the child abuse task force as it covers all aspects of fetal, neonatal and non-forensic postmortem imaging. The main focus of the task force is the guidance and standardization of non radiographic postmortem imaging, particularly postmortem CT and postmortem MRI. This manuscript outlines the starting point of the task force, with a mission statement, outline of current experience, and short- and long-term goals. PMID- 27412273 TI - Unravelling anisogamy: egg size and ejaculate size mediate selection on morphology in free-swimming sperm. AB - Gamete dimorphism (anisogamy) defines the sexes in most multicellular organisms. Theoretical explanations for its maintenance usually emphasize the size-related selection pressures of sperm competition and zygote survival, assuming that fertilization of all eggs precludes selection for phenotypes that enhance fertility. In external fertilizers, however, fertilization is often incomplete due to sperm limitation, and the risk of polyspermy weakens the advantage of high sperm numbers that is predicted to limit sperm size, allowing alternative selection pressures to target free-swimming sperm. We asked whether egg size and ejaculate size mediate selection on the free-swimming sperm of Galeolaria caespitosa, a marine tubeworm with external fertilization, by comparing relationships between sperm morphology and male fertility across manipulations of egg size and sperm density. Our results suggest that selection pressures exerted by these factors may aid the maintenance of anisogamy in external fertilizers by limiting the adaptive value of larger sperm in the absence of competition. In doing so, our study offers a more complete explanation for the stability of anisogamy across the range of sperm environments typical of this mating system and identifies new potential for the sexes to coevolve via mutual selection pressures exerted by gametes at fertilization. PMID- 27412274 TI - Acoustic telemetry and network analysis reveal the space use of multiple reef predators and enhance marine protected area design. AB - Marine protected areas (MPAs) are commonly employed to protect ecosystems from threats like overfishing. Ideally, MPA design should incorporate movement data from multiple target species to ensure sufficient habitat is protected. We used long-term acoustic telemetry and network analysis to determine the fine-scale space use of five shark and one turtle species at a remote atoll in the Seychelles, Indian Ocean, and evaluate the efficacy of a proposed MPA. Results revealed strong, species-specific habitat use in both sharks and turtles, with corresponding variation in MPA use. Defining the MPA's boundary from the edge of the reef flat at low tide instead of the beach at high tide (the current best in Seychelles) significantly increased the MPA's coverage of predator movements by an average of 34%. Informed by these results, the larger MPA was adopted by the Seychelles government, demonstrating how telemetry data can improve shark spatial conservation by affecting policy directly. PMID- 27412275 TI - Mutations in different pigmentation genes are associated with parallel melanism in island flycatchers. AB - The independent evolution of similar traits across multiple taxa provides some of the most compelling evidence of natural selection. Little is known, however, about the genetic basis of these convergent or parallel traits: are they mediated by identical or different mutations in the same genes, or unique mutations in different genes? Using a combination of candidate gene and reduced representation genomic sequencing approaches, we explore the genetic basis of and the evolutionary processes that mediate similar plumage colour shared by isolated populations of the Monarcha castaneiventris flycatcher of the Solomon Islands. A genome-wide association study (GWAS) that explicitly controlled for population structure revealed that mutations in known pigmentation genes are the best predictors of parallel plumage colour. That is, entirely black or melanic birds from one small island share an amino acid substitution in the melanocortin-1 receptor (MC1R), whereas similarly melanic birds from another small island over 100 km away share an amino acid substitution in a predicted binding site of agouti signalling protein (ASIP). A third larger island, which separates the two melanic populations, is inhabited by birds with chestnut bellies that lack the melanic MC1R and ASIP allelic variants. Formal FST outlier tests corroborated the results of the GWAS and suggested that strong, directional selection drives the near fixation of the MC1R and ASIP variants across islands. Our results, therefore, suggest that selection acting on different mutations with large phenotypic effects can drive the evolution of parallel melanism, despite the relatively small population size on islands. PMID- 27412276 TI - Neofunctionalization of embryonic head patterning genes facilitates the positioning of novel traits on the dorsal head of adult beetles. AB - The origin and integration of novel traits are fundamental processes during the developmental evolution of complex organisms. Yet how novel traits integrate into pre-existing contexts remains poorly understood. Beetle horns represent a spectacular evolutionary novelty integrated within the context of the adult dorsal head, a highly conserved trait complex present since the origin of insects. We investigated whether otd1/2 and six3, members of a highly conserved gene network that instructs the formation of the anterior end of most bilaterians, also play roles in patterning more recently evolved traits. Using ablation-based fate-mapping, comparative larval RNA interference (RNAi) and transcript sequencing, we found that otd1/2, but not six3, play a fundamental role in the post-embryonic formation of the adult dorsal head and head horns of Onthophagus beetles. By contrast, neither gene appears to pattern the adult head of Tribolium flour beetles even though all are expressed in the dorsal head epidermis of both Onthophagus and Tribolium We propose that, at least in beetles, the roles of otd genes during post-embryonic development are decoupled from their embryonic functions, and that potentially non-functional post-embryonic expression in the dorsal head facilitated their co-option into a novel horn patterning network during Onthophagus evolution. PMID- 27412277 TI - Acquired versus innate prey capturing skills in super-precocial live-bearing fish. AB - Live-bearing fish start hunting for mobile prey within hours after birth, an example of extreme precociality. Because prenatal, in utero, development of this behaviour is constrained by the lack of free-swimming sensory-motor interactions, immediate success after birth depends on innate, evolutionarily acquired patterns. Optimal performance however requires flexible adjustment to an unpredictable environment. To distinguish innate from postnatally developing patterns we analysed over 2000 prey capture events for 28 metallic livebearers (Girardinus metallicus; Poeciliidae), during their first 3 days after birth. We show that the use of synchronous pectoral fin beats for final acceleration and ingestion is fixed and presumably innate. It allows for direct, symmetrical control of swimming speed and direction, while avoiding head yaw. Eye movements and body curvatures, however, change considerably in the first few days, showing that eye-tail coordination requires postnatal development. The results show how successful prey captures for newborn, live-bearing fish are based on a combination of fixed motor programmes and rapid, postnatal development. PMID- 27412278 TI - Predator-driven brain size evolution in natural populations of Trinidadian killifish (Rivulus hartii). AB - Vertebrates exhibit extensive variation in relative brain size. It has long been assumed that this variation is the product of ecologically driven natural selection. Yet, despite more than 100 years of research, the ecological conditions that select for changes in brain size are unclear. Recent laboratory selection experiments showed that selection for larger brains is associated with increased survival in risky environments. Such results lead to the prediction that increased predation should favour increased brain size. Work on natural populations, however, foreshadows the opposite trajectory of evolution; increased predation favours increased boldness, slower learning, and may thereby select for a smaller brain. We tested the influence of predator-induced mortality on brain size evolution by quantifying brain size variation in a Trinidadian killifish, Rivulus hartii, from communities that differ in predation intensity. We observed strong genetic differences in male (but not female) brain size between fish communities; second generation laboratory-reared males from sites with predators exhibited smaller brains than Rivulus from sites in which they are the only fish present. Such trends oppose the results of recent laboratory selection experiments and are not explained by trade-offs with other components of fitness. Our results suggest that increased male brain size is favoured in less risky environments because of the fitness benefits associated with faster rates of learning and problem-solving behaviour. PMID- 27412279 TI - Rates of ecological divergence and body size evolution are correlated with species diversification in scaly tree ferns. AB - Variation in species richness across regions and between different groups of organisms is a major feature of evolution. Several factors have been proposed to explain these differences, including heterogeneity in the rates of species diversification and the age of clades. It has been frequently assumed that rapid rates of diversification are coupled to high rates of ecological and morphological evolution, leading to a prediction that remains poorly explored for most species: the positive association between ecological niche divergence, morphological evolution and species diversification. We combined a time calibrated phylogeny with distribution, ecological and body size data for scaly tree ferns (Cyatheaceae) to test whether rates of species diversification are predicted by the rates at which clades have evolved distinct ecological niches and body sizes. We found that rates of species diversification are positively correlated with rates of ecological and morphological evolution, with rapidly diversifying clades also showing rapidly evolving ecological niches and body sizes. Our results show that rapid diversification of scaly tree ferns is associated with the evolution of species with comparable morphologies that diversified into similar, yet distinct, environments. This suggests parallel evolutionary pathways opening in different tropical regions whenever ecological and geographical opportunities arise. Accordingly, rates of ecological niche and body size evolution are relevant to explain the current patterns of species richness in this 'ancient' fern lineage across the tropics. PMID- 27412280 TI - Crying wolf: limitations of predator-prey studies need not preclude their salient messages. PMID- 27412281 TI - Multi-trophic interactions in anthropogenic landscapes: the devil is in the detail. PMID- 27412282 TI - Nutrition shapes life-history evolution across species. AB - Nutrition is a key component of life-history theory, yet we know little about how diet quality shapes life-history evolution across species. Here, we test whether quantitative measures of nutrition are linked to life-history evolution across 96 species of butterflies representing over 50 independent diet shifts. We find that butterflies feeding on high nitrogen host plants as larvae are more fecund, but their eggs are smaller relative to their body size. Nitrogen and sodium content of host plants are also both positively related to eye size. Some of these relationships show pronounced lineage-specific effects. Testis size is not related to nutrition. Additionally, the evolutionary timing of diet shifts is not important, suggesting that nutrition affects life histories regardless of the length of time a species has been adapting to its diet. Our results suggest that, at least for some lineages, species with higher nutrient diets can invest in a range of fitness-related traits like fecundity and eye size while allocating less to each egg as offspring have access to a richer diet. These results have important implications for the evolution of life histories in the face of anthropogenic changes in nutrient availability. PMID- 27412283 TI - The association between religious homogamy and reproduction. AB - Individuals more strongly affiliated to religion have on average more children than less religious ones. Here, based on census data of 3 658 650 women aged 46 60 years from 32 countries provided by IPUMS International and data from the Wisconsin Longitudinal Study (n = 2400 women, aged 53-57 years), we show that religious homogamy is also associated with higher reproduction in terms of a higher number of children and a lower chance of remaining childless. We argue that, together with the relationship between general religious intensity and number of children, religious homogamy has reproductive consequences. These may impact future demographic developments and could have also played a role in the biological evolution of humans. PMID- 27412284 TI - Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria. AB - Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260-330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID- 27412285 TI - Proline as a fuel for insect flight: enhancing carbohydrate oxidation in hymenopterans. AB - Bees are thought to be strict users of carbohydrates as metabolic fuel for flight. Many insects, however, have the ability to oxidize the amino acid proline at a high rate, which is a unique feature of this group of animals. The presence of proline in the haemolymph of bees and in the nectar of plants led to the hypothesis that plants may produce proline as a metabolic reward for pollinators. We investigated flight muscle metabolism of hymenopteran species using high resolution respirometry performed on permeabilized muscle fibres. The muscle fibres of the honeybee, Apis mellifera, do not have a detectable capacity to oxidize proline, as those from the migratory locust, Locusta migratoria, used here as an outgroup representative. The closely related bumblebee, Bombus impatiens, can oxidize proline alone and more than doubles its respiratory capacity when proline is combined with carbohydrate-derived substrates. A distant wasp species, Vespula vulgaris, exhibits the same metabolic phenotype as the bumblebee, suggesting that proline oxidation is common in hymenopterans. Using a combination of mitochondrial substrates and inhibitors, we further show that in B. impatiens, proline oxidation provides reducing equivalents and electrons directly to the electron transport system. Together, these findings demonstrate that some bee and wasp species can greatly enhance the oxidation of carbohydrates using proline as fuel for flight. PMID- 27412286 TI - Calling in sick: impacts of fever on intra-urban human mobility. AB - Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A retrospective, semi-structured interview allowed us to quantify multiple aspects of mobility during the two-week period preceding each interview. We fitted nested models of each aspect of mobility to data from interviews and compared models using likelihood ratio tests to determine whether there were statistically distinguishable differences in mobility attributable to fever or its aetiology. Compared with afebrile individuals, febrile study participants spent more time at home, visited fewer locations, and, in some cases, visited locations closer to home and spent less time at certain types of locations. These multifaceted impacts are consistent with the possibility that disease-mediated changes in host mobility generate dynamic and complex changes in host contact network structure. PMID- 27412287 TI - Improving the outcome of fractional CO2 laser resurfacing using a probiotic skin cream: Preliminary clinical evaluation. AB - As known, fractional CO2 resurfacing treatments are more effective than non ablative ones against aging signs, but post-operative redness and swelling prolong the overall downtime requiring up to steroid administration in order to reduce these local systems. In the last years, an increasing interest has been focused on the possible use of probiotics for treating inflammatory and allergic conditions suggesting that they can exert profound beneficial effects on skin homeostasis. In this work, the Authors report their experience on fractional CO2 laser resurfacing and provide the results of a new post-operative topical treatment with an experimental cream containing probiotic-derived active principles potentially able to modulate the inflammatory reaction associated to laser-treatment. The cream containing DermaACB (CERABESTTM) was administered post operatively to 42 consecutive patients who were treated with fractional CO2 laser. All patients adopted the cream twice a day for 2 weeks. Grades were given according to outcome scale. The efficacy of the cream containing DermaACB was evaluated comparing the rate of post-operative signs vanishing with a control group of 20 patients topically treated with an antibiotic cream and a hyaluronic acid based cream. Results registered with the experimental treatment were good in 22 patients, moderate in 17, and poor in 3 cases. Patients using the study cream took an average time of 14.3 days for erythema resolution and 9.3 days for swelling vanishing. The post-operative administration of the cream containing DermaACB induces a quicker reduction of post-operative erythema and swelling when compared to a standard treatment. PMID- 27412288 TI - Laser phototherapy improves early stage of cutaneous wound healing of rats under hyperlipidic diet. AB - The aim of this study was to evaluate the influence of laser photobiomodulation in cutaneous healing of rats under a hyperlipidic diet. Forty-eight Wistar Albinus rats, weaned, received standard diet (SD) or hyperlipidic diet (HD) for 20 weeks. The groups were divided into SD rats and HD rats, SD-irradiated rats (LSD), and HD-irradiated rats (LHD). Standard cutaneous wound (1 cm(2)) was created on the dorsum of each rat. The irradiation started immediately after surgery and every 48 h for 7 or 14 days (lambda660 nm, 40 mW, 6 J/cm(2), phi 0,04 cm(2), CW), when they were killed under deep anesthesia. The specimens were removed, routinely processed, stained with hematoxylin/eosin (H/E), and evaluated by light microscopy. Rats fed with hyperlipidic diet had greater intensity in the inflammatory process and prolonged hyperemia. At day 7, the intensity of inflammation was reduced in LSD and LHD groups when compared to their control groups, SD (p = 0.002) and HD (p = 0.02). There was an increase in fibroblast proliferation and collagen deposition, especially in the LHD group. At day 14, the HD group presented more intensive hyperemia than the SD group. It can be concluded that the hyperlipidic diet modified the inflammation pattern in wound healing and that laser light has a positive biomodulative effect on the healing process only in early stages. PMID- 27412289 TI - Minimally invasive curved-micro-drainer (CMD) capable of innocuous drainage of subretinal fluid for the treatment of retinal detachment. AB - Retinal detachment is a serious vision threatening disease. Current consensus for the treatment of retinal detachment is to reattach the retina onto the choroid layer by drainage of accumulated subretinal fluid. Although several surgical methods have been developed, no satisfactory visual outcome has been obtained without surgical complications such as unintended puncture and hemorrhage of the retina and choroid tissue. In this study, we developed a novel Curved-Micro Drainer (CMD) for the innocuous drainage of subretinal fluid. It is a curved structure with a 15 degrees beveled tip that is 5 mm in length, with an 80 MUm inner diameter and a 100 MUm outer diameter. This high inner-to-outer diameter ratio of CMD with a 100 MUm outer diameter allows efficient drainage of highly viscous subretinal fluid in a minimally invasive manner. In addition, the curved structure precisely matches the spherical ocular structure, which facilitates the CMD insertion into the subretinal space without choroid tissue damage. We demonstrate that the optimized CMD allows for the innocuous drainage of the viscous subretinal fluid from the porcine eye, whereas the traditional hypodermic needle (31-gauge) induces severe retinal and choroid damage. CMD can overcome a critical safety issue and is a potential alternative to conventional surgical interventions for the innocuous drainage of subretinal fluid. PMID- 27412290 TI - Ethnic differences in oral health and use of dental services: cross-sectional study using the 2009 Adult Dental Health Survey. AB - BACKGROUND: Oral health impacts on general health and quality of life, and oral diseases are the most common non-communicable diseases worldwide. Non-White ethnic groups account for an increasing proportion of the UK population. This study explores whether there are ethnic differences in oral health and whether these are explained by differences in sociodemographic or lifestyle factors, or use of dental services. METHODS: We used the Adult Dental Health Survey 2009 to conduct a cross-sectional study of the adult general population in England, Wales and Northern Ireland. Ethnic groups were compared in terms of oral health, lifestyle and use of dental services. Logistic regression analyses were used to determine whether ethnic differences in fillings, extractions and missing teeth persisted after adjustment for potential sociodemographic confounders and whether they were explained by lifestyle or dental service mediators. RESULTS: The study comprised 10,435 (94.6 %) White, 272 (2.5 %) Indian, 165 (1.5 %) Pakistani/Bangladeshi and 187 (1.7 %) Black participants. After adjusting for confounders, South Asian participants were significantly less likely, than White, to have fillings (Indian adjusted OR 0.25, 95 % CI 0.17-0.37; Pakistani/Bangladeshi adjusted OR 0.43, 95 % CI 0.26-0.69), dental extractions (Indian adjusted OR 0.33, 95 % CI 0.23-0.47; Pakistani/Bangladeshi adjusted OR 0.41, 95 % CI 0.26-0.63), and <20 teeth (Indian adjusted OR 0.31, 95 % CI 0.16 0.59; Pakistani/Bangladeshi adjusted OR 0.22, 95 % CI 0.08-0.57). They attended the dentist less frequently and were more likely to add sugar to hot drinks, but were significantly less likely to consume sweets and cakes. Adjustment for these attenuated the differences but they remained significant. Black participants had reduced risk of all outcomes but after adjustment for lifestyle the difference in fillings was attenuated, and extractions and tooth loss became non-significant. CONCLUSIONS: Contrary to most health inequalities, oral health was better among non-White groups, in spite of lower use of dental services. The differences could be partially explained by reported differences in dietary sugar. PMID- 27412292 TI - Modeling and simulation of maintenance treatment in first-line non-small cell lung cancer with external validation. AB - BACKGROUND: Maintenance treatment (MTx) in responders following first-line treatment has been investigated and practiced for many cancers. Modeling and simulation may support interpretation of interim data and development decisions. We aimed to develop a modeling framework to simulate overall survival (OS) for MTx in NSCLC using tumor growth inhibition (TGI) data. METHODS: TGI metrics were estimated using longitudinal tumor size data from two Phase III first-line NSCLC studies evaluating bevacizumab and erlotinib as MTx in 1632 patients. Baseline prognostic factors and TGI metric estimates were assessed in multivariate parametric models to predict OS. The OS model was externally validated by simulating a third independent NSCLC study (n = 253) based on interim TGI data (up to progression-free survival database lock). The third study evaluated pemetrexed + bevacizumab vs. bevacizumab alone as MTx. RESULTS: Time-to-tumor growth (TTG) was the best TGI metric to predict OS. TTG, baseline tumor size, ECOG score, Asian ethnicity, age, and gender were significant covariates in the final OS model. The OS model was qualified by simulating OS distributions and hazard ratios (HR) in the two studies used for model-building. Simulations of the third independent study based on interim TGI data showed that pemetrexed + bevacizumab MTx was unlikely to significantly prolong OS vs. bevacizumab alone given the current sample size (predicted HR: 0.81; 95 % prediction interval: 0.59 1.09). Predicted median OS was 17.3 months and 14.7 months in both arms, respectively. These simulations are consistent with the results of the final OS analysis published 2 years later (observed HR: 0.87; 95 % confidence interval: 0.63-1.21). Final observed median OS was 17.1 months and 13.2 months in both arms, respectively, consistent with our predictions. CONCLUSIONS: A robust TGI-OS model was developed for MTx in NSCLC. TTG captures treatment effect. The model successfully predicted the OS outcomes of an independent study based on interim TGI data and thus may facilitate trial simulation and interpretation of interim data. The model was built based on erlotinib data and externally validated using pemetrexed data, suggesting that TGI-OS models may be treatment-independent. The results supported the use of longitudinal tumor size and TTG as endpoints in early clinical oncology studies. PMID- 27412291 TI - Pim1 inhibition as a novel therapeutic strategy for Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Clinically, AD is characterized by impairments of memory and cognitive functions. Accumulation of amyloid-beta (Abeta) and neurofibrillary tangles are the prominent neuropathologies in patients with AD. Strong evidence indicates that an imbalance between production and degradation of key proteins contributes to the pathogenesis of AD. The mammalian target of rapamycin (mTOR) plays a key role in maintaining protein homeostasis as it regulates both protein synthesis and degradation. A key regulator of mTOR activity is the proline-rich AKT substrate 40 kDa (PRAS40), which directly binds to mTOR and reduces its activity. Notably, AD patients have elevated levels of phosphorylated PRAS40, which correlate with Abeta and tau pathologies as well as cognitive deficits. Physiologically, PRAS40 phosphorylation is regulated by Pim1, a protein kinase of the protoconcogene family. Here, we tested the effects of a selective Pim1 inhibitor (Pim1i), on spatial reference and working memory and AD-like pathology in 3xTg-AD mice. RESULTS: We have identified a Pim1i that crosses the blood brain barrier and reduces PRAS40 phosphorylation. Pim1i-treated 3xTg-AD mice performed significantly better than their vehicle treated counterparts as well as non transgenic mice. Additionally, 3xTg-AD Pim1i-treated mice showed a reduction in soluble and insoluble Abeta40 and Abeta42 levels, as well as a 45.2 % reduction in Abeta42 plaques within the hippocampus. Furthermore, phosphorylated tau immunoreactivity was reduced in the hippocampus of Pim1i-treated 3xTg-AD mice by 38 %. Mechanistically, these changes were linked to a significant increase in proteasome activity. CONCLUSION: These results suggest that reductions in phosphorylated PRAS40 levels via Pim1 inhibition reduce Abeta and Tau pathology and rescue cognitive deficits by increasing proteasome function. Given that Pim1 inhibitors are already being tested in ongoing human clinical trials for cancer, the results presented here may open a new venue of drug discovery for AD by developing more Pim1 inhibitors. PMID- 27412293 TI - Electrosmog and autoimmune disease. AB - Studies in mice have shown that environmental electromagnetic waves tend to suppress the murine immune system with a potency similar to NSAIDs, yet the nature of any Electrosmog effects upon humans remains controversial. Previously, we reported how the human Vitamin-D receptor (VDR) and its ligand, 1,25 dihydroxyvitamin-D (1,25-D), are associated with many chronic inflammatory and autoimmune diseases. We have shown how olmesartan, a drug marketed for mild hypertension, acts as a high-affinity partial agonist for the VDR, and that it seems to reverse disease activity resulting from VDR dysfunction. We here report that structural instability of the activated VDR becomes apparent when observing hydrogen bond behavior with molecular dynamics, revealing that the VDR pathway exhibits a susceptibility to Electrosmog. Further, we note that characteristic modes of instability lie in the microwave frequency range, which is currently populated by cellphone and WiFi communication signals, and that the susceptibility is ligand dependent. A case series of 64 patient-reported outcomes subsequent to use of a silver-threaded cap designed to protect the brain and brain stem from microwave Electrosmog resulted in 90 % reporting "definite" or "strong" changes in their disease symptoms. This is much higher than the 3-5 % rate reported for electromagnetic hypersensitivity in a healthy population and suggests that effective control of environmental Electrosmog immunomodulation may soon become necessary for successful therapy of autoimmune disease. PMID- 27412294 TI - Severe manifestations of autoimmune syndrome induced by adjuvants (Shoenfeld's syndrome). AB - Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to previous exposure to an adjuvant substance. The clinical picture is very heterogeneous, from mild to severe manifestations, including death. However, the systematic analysis of severe ASIA cases has not been performed. The aim of this study was to systematically review the literature on severe ASIA cases. A systematic review of the literature was performed investigating severe ASIA cases. All publications were identified through PubMed, EMBASE, MEDLINE and Cochrane. Articles published from 2011 to 2016 were included. Severe ASIA was arbitrarily defined as follows: major organ involvement, life threatening conditions, intensive treatment, disability, hospitalization and outcome (survival and death). Cases described before 2011 were excluded. From 2011 to 2016, we identified 4479 ASIA cases, of them 305 fulfilled arbitrary criteria of severe ASIA including our case presentation and 11 deaths. The majority of severe ASIA cases were related to HPV vaccine, silicone, influenza vaccine and mineral oil injections. The interval from exposition to severe manifestation was from 2 days to 23 years. (1) This is the first study that analyzes all cases published on ASIA with severe manifestations. (2) The current HPV vaccine is both effective and generally safe. However, it should be noted that severe autoimmune side effects have been reported in several studies. Severe ASIA may be observed after influenza vaccines, and other vaccines. (3) Efforts should be made to discover the connection between adjuvants, autoimmunity and autoimmune diseases, because there is an increase in cases severe and life threatening of ASIA. PMID- 27412295 TI - Is explantation of silicone breast implants useful in patients with complaints? AB - In this review, we present a critical review of the existing literature reflecting the results of explantation of silicone breast implants in patients with silicone-related complaints and/or autoimmune diseases. A literature search was performed to discuss the following issues: which clinical manifestations and autoimmune diseases improve after explantation, and what is the course of these complaints after explantation. Next, we reviewed studies in which the effect of explantation on laboratory findings observed in patients with silicone breast implants was studied, and lastly, we reviewed studies that described the effect of reconstruction of the breast with a new implant or autologous tissue after explantation. We calculated from the literature that explantation of the silicone breast improved silicone-related complaints in 75 % of the patients (469 of 622). In patients with autoimmune diseases, however, improvement was only infrequently observed without additional therapy with immunosuppressive therapy, i.e., in 16 % of the patients (3 of 18). The effect of explantation did not influence autoantibody testing such as ANA. We discuss several possibilities which could clarify why patients improve after explantation. Firstly, the inflammatory response could be reduced after explantation. Secondly, explantation of the implants may remove a nociceptive stimulus, which may be the causative factor for many complaints. Options for reconstruction of the explanted breast are autologous tissue and/or water-/hydrocellulose-filled breast implant. Unfortunately, in very few studies attention was paid to reconstructive possibilities. Therefore, no adequate conclusion regarding this issue could be drawn. In conclusion, explantation is useful for improvement of silicone-related complaints in 75 % of the patients, whereas in patients who developed autoimmune diseases improvement is only observed when explantation is combined with immunosuppressive therapy. In a patient with silicone-related complaints in which explantation is considered, the patient should be counseled for the different options of reconstruction after explantation. PMID- 27412296 TI - Family medicine resident OSCEs: a systematic review. AB - BACKGROUND AND OBJECTIVES: Family Medicine trainees are often assessed in Objective Structured Clinical Examinations (OSCEs). The purpose of this survey is to document the quality in terms of psychometrics and standard setting of OSCEs as used in Family Practice (FP)/General Practice (GP) training programs. METHODS: Nine electronic data bases were searched from inception to December 2015 and included articles were searched in the PubMed single citation matcher. Two authors independently assessed all titles/abstracts/full texts and abstracted data. Articles were searched for OSCEs used for performance assessment of FP/GP trainees. RESULTS: Twenty-one studies were identified which met our criteria published between 1987 and 2014. Content validity was reported in 18, construct validity in nine, and criterion (concurrent and/or predictive) validity in five. Five articles considered the consequences of testing. Internal reliability was reported by 12 studies, inter-rater reliability by seven, generalisability by four. Nine set pass-fail standards of which four were by criterion standards. In addition, we tabulated sources of validity and reliability as with particular reference to medical education. CONCLUSIONS: We found few articles which vigorously provided evidence of validity and reliability. Standard-setting, when done, was normative in all high stakes exams. OSCEs used for formative purposes had lower psychometric standards. PMID- 27412297 TI - "The Theory was Beautiful Indeed": Rise, Fall and Circulation of Maximizing Methods in Population Genetics (1930-1980). AB - Describing the theoretical population geneticists of the 1960s, Joseph Felsenstein reminisced: "our central obsession was finding out what function evolution would try to maximize. Population geneticists used to think, following Sewall Wright, that mean relative fitness, W, would be maximized by natural selection" (Felsenstein 2000). The present paper describes the genesis, diffusion and fall of this "obsession", by giving a biography of the mean fitness function in population genetics. This modeling method devised by Sewall Wright in the 1930s found its heyday in the late 1950s and early 1960s, in the wake of Motoo Kimura's and Richard Lewontin's works. It seemed a reliable guide in the mathematical study of deterministic effects (the study of natural selection in populations of infinite size, with no drift), leading to powerful generalizations presenting law-like properties. Progress in population genetics theory, it then seemed, would come from the application of this method to the study of systems with several genes. This ambition came to a halt in the context of the influential objections made by the Australian mathematician Patrick Moran in 1963. These objections triggered a controversy between mathematically- and biologically-inclined geneticists, with affected both the formal standards and the aims of population genetics as a science. Over the course of the 1960s, the mean fitness method withered with the ambition of developing the deterministic theory. The mathematical theory became increasingly complex. Kimura re-focused his modeling work on the theory of random processes; as a result of his computer simulations, Lewontin became the staunchest critic of maximizing principles in evolutionary biology. The mean fitness method then migrated to other research areas, being refashioned and used in evolutionary quantitative genetics and behavioral ecology. PMID- 27412298 TI - An unusual recruitment strategy in a mass-recruiting stingless bee, Partamona orizabaensis. AB - Foragers of several stingless bee species deposit attractive scent marks on solid substrates to precisely recruit nestmates to food. Interestingly, Partamona workers quickly recruit large numbers of nest mates to resources, likely even without the deposition of attractive scent marks. However, systematic studies of the recruitment system of these bees are lacking. We now studied the recruitment behavior of P. orizabaensis. Our findings show that foragers of this species can recruit large numbers of nestmates to food sources at a particular location. The precise nestmate recruitment does not rely on attractive scent marks deposited on substrates. We never observed any scent marking behavior and feeders baited with labial or mandibular gland extracts were not attractive for the bees. Chemical analyses showed that the foragers' labial gland secretions exclusively contain long chain hydrocarbons, which render their role in recruitment communication unlikely. Whether mandibular gland secretions, which contain esters and alcohols that are known as attractive pheromones in other bee species, are used to guide recruits toward food during flight, remains elusive. We conclude that Partamona's quick recruitment system that does not rely on conspicuous scent marks has evolved as a strategy against competition with sympatrically occurring and more aggressive bee species. PMID- 27412300 TI - Endothelial RAGE exacerbates acute postischaemic cardiac inflammation. AB - Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 +/- 4 cells/hpf) was significantly reduced in ICAM-1-/- (40 +/- 3 cells/hpf) and RAGE-/- mice (38 +/- 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 +/- 3 cells/hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28 %), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55 %). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 +/- 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/ BM) leucocyte retention was significantly reduced (13 +/- 1 cells/hpf), similar to non-transplanted ICAM/RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 +/- 4 mmHg vs 86 +/- 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion. RAGE represents an additional pro inflammatory endothelial mediator of ischaemia-reperfusion injury. PMID- 27412301 TI - Do Advanced Glycation End Products (AGEs) Contribute to the Comorbidities of Polycystic Ovary Syndrome (PCOS)? AB - Advanced glycation end products (AGEs) are formed both during the endogenous and exogenous reactions and are implicated in the process of ageing, pathogenesis of diabetes, atherosclerosis, female fertility, and cancers. Food and smoking are the most important sources of exogenous AGEs in daily life. The biochemical composition of meal, cooking methods, time and temperature of food preparation may impact AGEs formation, therefore Western-type diet, rich in animal-derived products as well as in fast foods seems to be the main source of AGEs. Both, endogenous and exogenous AGEs can act intracellularly or during serum interaction with cell surface receptors called RAGE influencing variety of molecular pathways. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. The aetiology of this disorder remains unclear, however the environmental and genetic factors may play an important role in its pathogenesis. Nevertheless, PCOS women have increased factors for reproductive and cardiometabolic comorbidities. AGEs can contribute to the pathogenesis of PCOS as well as its consequences. It has been shown that chronic inflammation and increased oxidative stress may be a link between the mechanisms of AGEs action and the metabolic and reproductive consequences of PCOS. This review highlights that high dietary AGEs intake promotes deteriorating biological effects in women with PCOS, whereas AGEs restriction seems to have beneficial impact on women health. Better understanding AGEs formation and biochemistry as well as AGE mediated pathophysiological mechanisms may open new therapeutic avenues converging to the achievement of the complete treatment of PCOS and its consequences. PMID- 27412299 TI - Can Sierra Leone maintain the equitable delivery of their Free Health Care Initiative? The case for more contextualised interventions: results of a cross sectional survey. AB - BACKGROUND: In 2010, the Ministry of Health and Sanitation in Sierra Leone launched their Free Health Care Initiative (FHCI) for pregnant and lactating mothers and children under-5. Despite an increase in the update of services, the inequitable distribution of health services and health facilities remain important factors underlying the poor performance of health systems to deliver effective services. This study identifies current gaps in service delivery across two rural locations served by the same District Health Management Team (DHMT). METHODS: We employed a cross-sectional household survey using a two-stage probability sampling method to obtain a sample of the population across two rural locations in Bonthe District: the riverine and the mainland. Overall, a total of 393 households across 121 villages were surveyed in the riverine and 397 households across 130 villages were sampled on the mainland. Maternal health, child health and sanitation indicators in Bonthe District were compared using Pearson Chi-Squared test with Yates' Continuity Correction across the two areas. RESULTS: Women across the two regions self-reported significantly different uptake of family planning services. Children on the mainland had significantly greater rates of health facility based deliveries; being born in the presence of a skilled birth attendant; completed immunisation schedules; and higher rates of being brought to the health centre within 24 h of developing a fever or a suspected acute respiratory infection. Households on the mainland also reported significantly greater use of treated water and unrestricted access to a latrine. CONCLUSIONS: If the government of Sierra Leone is going to deliver on their promise to free health care for pregnant women and their children, and do so in a way that reduces inequalities, greater attention must be paid to the existing service delivery gaps within each District. This is particularly relevant to health policy post-Ebola, as it highlights the need for more contextualised service delivery to ensure equitable access for women and children. PMID- 27412307 TI - Methodology for Quantitative Characterization of Fluorophore Photoswitching to Predict Superresolution Microscopy Image Quality. AB - Single-molecule localization microscopy (SMLM) image quality and resolution strongly depend on the photoswitching properties of fluorophores used for sample labeling. Development of fluorophores with optimized photoswitching will considerably improve SMLM spatial and spectral resolution. Currently, evaluating fluorophore photoswitching requires protein-conjugation before assessment mandating specific fluorophore functionality, which is a major hurdle for systematic characterization. Herein, we validated polyvinyl alcohol (PVA) as a single-molecule environment to efficiently quantify the photoswitching properties of fluorophores and identified photoswitching properties predictive of quality SMLM images. We demonstrated that the same fluorophore photoswitching properties measured in PVA films and using antibody adsorption, a protein-conjugation environment analogous to labeled cells, were significantly correlated to microtubule width and continuity, surrogate measures of SMLM image quality. Defining PVA as a fluorophore photoswitching screening platform will facilitate SMLM fluorophore development and optimal image buffer assessment through facile and accurate photoswitching property characterization, which translates to SMLM fluorophore imaging performance. PMID- 27412309 TI - Individualized Late-Life Care. PMID- 27412308 TI - Photo-thermionic effect in vertical graphene heterostructures. AB - Finding alternative optoelectronic mechanisms that overcome the limitations of conventional semiconductor devices is paramount for detecting and harvesting low energy photons. A highly promising approach is to drive a current from the thermal energy added to the free-electron bath as a result of light absorption. Successful implementation of this strategy requires a broadband absorber where carriers interact among themselves more strongly than with phonons, as well as energy-selective contacts to extract the excess electronic heat. Here we show that graphene-WSe2-graphene heterostructure devices offer this possibility through the photo-thermionic effect: the absorbed photon energy in graphene is efficiently transferred to the electron bath leading to a thermalized hot carrier distribution. Carriers with energy higher than the Schottky barrier between graphene and WSe2 can be emitted over the barrier, thus creating photocurrent. We experimentally demonstrate that the photo-thermionic effect enables detection of sub-bandgap photons, while being size-scalable, electrically tunable, broadband and ultrafast. PMID- 27412310 TI - A Doctor's Case for Medical Marijuana. PMID- 27412311 TI - Antibiotic Stewardship in Long-Term Care: A Call to Action. AB - The Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention are focused heavily on curbing the misuse of antibiotics in health care facilities. Regulations governing the management of antibiotics in the nursing facility will likely be changing in the near future, which will put the pharmacist at the forefront of a clinical team that is dedicated to proper antibiotic utilization. Savvy pharmacists are embracing this opportunity to engage long-term care facility staff to improve the care of their residents. PMID- 27412312 TI - Key Value Considerations for Consultant Pharmacists. AB - Managing the efficiency and costs of residents' drug regimens outside the acute care hospital and through transitions of care requires a toolbox filled with cost control tools and careful collaboration among the pharmacy provider(s), facility staff, and the consultant/senior care pharmacist. This article will provide the reader with key long-term care business strategies that affect the profitability of the pharmacy provider in various care settings while, at the same time, ensuring optimal therapy for residents as they transition across levels of care. Readers can take away ideas on how to access critical information, what they can do with this information, and how they can improve the overall care process. Four experts in various aspects of pharmacy management share their insights on pharmacy practice issues including formulary management, performance metrics, short-cycle dispensing challenges/solutions, cost-control measures, facility surveys, billing practices, medication reconciliation, prospective medication reviews, and transitions of care. PMID- 27412313 TI - A Patient's Last Wish at the End-of-Life. AB - INTRODUCTION: Patients who have transitioned to end-of-life (EOL) care are at an increased risk for polypharmacy as they face new symptoms requiring palliative care medications. CASE: The patient was a 96-year-old, 6' 2", 125-pound male patient who was brought into the outpatient geriatric practice by his daughter, with whom he had been living all his life. The patient had no pain, but severe dysphagia. Both daughter and patient were fully aware that death was imminent, as the patient had lost 60 pounds in the past three to four months because of gastrointestinal cancer. The daughter asked if she could stop any of his medications, which she had been struggling to provide because of his dysphagia; Her bed-bound father was anorectic; at that point the geriatrician called for a pharmacy consult, specifically to address the issue of unnecessary medications. DISCUSSION: There is little evidence or guidance in reducing or discontinuing medications for chronic illnesses during EOL care. While it is understandable that the number of symptom-relief medications will increase, patient comfort can be helped by reducing maintenance medications that have little to no short-term benefit. CONCLUSION: As EOL approaches, a patient's last wishes must be respected, including timely changes to his or her medication regimen. Pharmacists are an essential asset to the geriatric interdisciplinary team, as they can provide extensive medication counseling. PMID- 27412314 TI - Updated Nitrofurantoin Recommendations in the Elderly: A Closer Look at the Evidence. AB - The American Geriatrics Society 2015 Beers Criteria Update Expert Panel has revised its recommendation to avoid use of nitrofurantoin in renal impairment from patients with a creatinine clearance (Clcr) of less than 60 mL/min to those with a Clcr of less than 30 mL/min, based on two retrospective studies that identified the safety and efficacy of nitrofurantoin in this population. This change in recommendation, along with increasing resistance to both sulfamethoxazole/trimethoprim and fluoroquinolones, gave rise to the advantages of nitrofurantoin and may reflect a surge in prescribing among the elderly. The purpose of the manuscript is to provide readers with a brief review of updated evidence to confidently treat older patients with nitrofurantoin. PMID- 27412315 TI - Medication Use, Falls, and Fall-Related Worry in Older Adults in the United States. AB - OBJECTIVE: To compare the prevalence of falls and fall-related concerns of medication users versus nonusers in U.S. seniors. DESIGN: Cross-sectional study. SETTING: The National Health and Aging Trends Study. PARTICIPANTS: U.S. nationally representative sample of Medicare beneficiaries in 2011. OUTCOMES: Comparing subjects who used medications with subjects who did not in the past month, the outcomes were percentages of subjects who experienced 1) a fall in the past month, 2) worry about falling in the past month, 3) being limited by this worry in the past month, 4) a fall in the past year. RESULTS: A greater percentage of medication users experienced falls and fall-related outcomes, compared with non-medication users. Among medication users, 10.29% had a past month fall, compared with 5.42% of non-medication users; 27.69% of medication users worried in the past month about falling, compared with 9.15% of non medication users; 40.96% of medication users were limited by this worry, compared with 21.21%; 22.82% of medication users had a fall in the past year, compared with 13.15% of non-medication users. CONCLUSION: Seniors who use medications are more likely to fall and to be concerned about falling. Pharmacist involvement in fall prevention continues to be essential. PMID- 27412316 TI - Phonological acquisition of Korean consonants in conversational speech produced by young Korean children. AB - This study investigates the phonological acquisition of Korean consonants using conversational speech samples collected from sixty monolingual typically developing Korean children aged two, three, and four years. Phonemic acquisition was examined for syllable-initial and syllable-final consonants. Results showed that Korean children acquired stops and nasals followed by affricates, fricatives, and the liquid. In general, Korean consonants were acquired earlier in syllable-initial position compared to syllable-final position, except for the liquid /l/. The findings are compared with previous research based on single-word assessments, and differences that appear to be associated with the unique morphological system of Korean are noted. PMID- 27412317 TI - Neurobehavioral Effects of Consuming Dietary Fatty Acids. AB - BACKGROUND: Research results on the neurobehavioral effects of consuming dietary fatty acids are mixed. Therefore, this study examined the effects of consuming dietary fatty acids on depression, mood, and anxiety. METHODS: In this randomized crossover-design study, 37 university students served as their own controls, consuming each of the following diets for a 4-day period with a 2-week washout period between diets: (1) low fatty acid, (2) high saturated fatty acid (SFA), (3) high polyunsaturated fatty acid (PUFA), and (4) control. The order of sessions was counterbalanced across dietary groups. Following consumption of each diet, participants were examined for within-subject differences in depression, mood, and anxiety. Measures included weighed dietary fat intakes, Zung's Self Rating Anxiety and Depression Scales, and the Positive and Negative Affect Schedule. RESULTS: Participants had significantly higher positive affect scores (p < .007) and were significantly less irritable (p < .04) when they consumed diets rich in SFAs and PUFAs than when they consumed a low fatty acid or control diet. However, depression, anxiety, and negative affect scores did not differ significantly among diets. Analysis of participants' serum lipid levels following their intake of the fatty acid and control diets indicated significantly higher levels of total cholesterol (p = .006) and serum triglycerides (p = .003) with the control diet. CONCLUSIONS: These results highlight the neurobehavioral benefits of consuming dietary fatty acids among healthy individuals. By concentrating on the positive effects of diet on affective processes, health professionals can also provide support for at-risk individuals. PMID- 27412319 TI - Development of Minimally Invasive Pancreatic Surgery: an Evidence-Based Systematic Review of Laparoscopic Versus Robotic Approaches. AB - INTRODUCTION: Laparoscopic and robotic surgery of the pancreas has only recently emerged as viable treatment options for benign and malignant disease. This review seeks to evaluate the current body of evidence on these approaches to pancreaticoduodenectomy and distal pancreatectomy. METHODS: A systematic review of large published series was performed utilizing the PubMed search engine. RESULTS: Based on these reports, both the laparoscopic and robotic techniques for these complex procedures appear to be safe and effective, if performed by high volume experienced pancreatic surgeons. The advantages of each approach are highlighted, emphasizing the data available on the learning curve and potential dissemination. CONCLUSIONS: Both minimally invasive approaches to pancreatic resection are safe and feasible. PMID- 27412318 TI - A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma. AB - INTRODUCTION: Although widely used, the 7th edition American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (PHC) may be limited. Disease-specific nomograms have been proposed as a better means to predict long-term survival for individual patients. We sought to externally validate a recently proposed nomogram by Memorial Sloan Kettering Cancer Center (MSKCC) for PHC, as well as identify factors to improve the prediction of prognosis for patients with PHC. METHODS: Four hundred seven patients who underwent surgery for PHC between 1988 and 2014 were identified using an international, multi-center database. Standard clinicopathologic and outcome data were collected. The predictive power of the AJCC staging system and nomogram were assessed. RESULTS: Median survival was 24.4 months; 3- and 5-year survival was 37.2 and 20.8 %, respectively. The AJCC 7th edition staging system (C-index 0.570) and the recently proposed PHC nomogram (C-index 0.587) both performed poorly. A revised nomogram based on age, lymphovascular invasion, perineural invasion, and lymph node metastases performed better (C-index 0.682). The calibration plot of the revised PHC nomogram demonstrated good calibration. CONCLUSION: The 7th edition AJCC staging system and the MSKCC nomogram had a poor ability to predict long-term survival for individual patients with PHC. A revised nomogram provided more accurate prediction of survival, but will need to be externally validated. PMID- 27412320 TI - Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: a Systematic Review and Meta-analysis. AB - INTRODUCTION: The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis. MATERIAL AND METHODS: Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients' prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE-). The data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for potential confounders. RESULTS: Nine studies followed up 3250 patients with gastric cancer (1064 ENE+ and 2186 ENE-). ENE+ was associated with a significantly higher risk of all-cause mortality (RR = 1.70; 95 % CI: 1.43-2.03, I (2) = 66 %; HR = 2.14; 95 % CI: 1.66-2.75, I (2) = 0 %), cancer-specific mortality (RR = 1.59; 95 % CI: 1.42-1.79; HR = 1.52; 95 % CI: 1.19-1.96), and disease recurrence (RR = 3.43, 95 % CI: 1.80-6.54, I (2) = 0 %). DISCUSSION: Judging from our results, ENE in gastric cancer patients should be considered for prognostic purposes from the gross sample to the pathology report. PMID- 27412322 TI - Application of a hybrid ordered mesoporous silica as sorbent for solid-phase multi-residue extraction of veterinary drugs in meat by ultra-high-performance liquid chromatography coupled to ion-trap tandem mass spectrometry. AB - A quick, sensitive and selective analytical reversed-phase multi-residue method using ultra-high performance liquid chromatography coupled to an ion-trap mass spectrometry detector (UHPLC-IT-MS/MS) operating in both positive and negative ion mode was developed for the simultaneous determination of 23 veterinary drug residues (beta-blockers, beta-agonists and Non-Steroidal Anti-inflammatory Drugs (NSAIDs)) in meat samples. The sample treatment involved a liquid-solid extraction followed by a solid-phase extraction (SPE) procedure. SBA-15 type mesoporous silica was synthetized and modified with octadecylsilane, and the resulting hybrid material (denoted as SBA-15-C18) was applied and evaluated as SPE sorbent in the purification of samples. The materials were comprehensively characterized, and they showed a high surface area, high pore volume and a homogeneous distribution of the pores. Chromatographic conditions and extraction procedure were optimized, and the method was validated according to the Commission Decision 2002/657/EC. The method detection limits (MDLs) and the method quantification limits (MQLs) were determined for all the analytes in meat samples and found to range between 0.01-18.75MUg/kg and 0.02-62.50MUg/kg, respectively. Recoveries for 15 of the target analytes ranged from 71 to 98%. In addition, for comparative purpose SBA-15-C18 was evaluated towards commercial C18 amorphous silica. Results revealed that SBA-15-C18 was clearly more successful in the multi-residue extraction of the 23 mentioned analytes with higher recovery values. The method was successfully tested to analyze prepacked preparations of mince bovine meat. Traces of propranolol, ketoprofen and diclofenac were detected in some samples. PMID- 27412321 TI - Minimally Invasive vs. Open Hepatectomy: a Comparative Analysis of the National Surgical Quality Improvement Program Database. AB - BACKGROUND: While minimally invasive surgery (MIS) to treat liver tumors has increased, data on perioperative outcomes of MIS relative to open liver resection (O-LR) are lacking. We sought to compare short-term outcomes among patients undergoing MIS vs. O-LR in a nationally representative database. METHODS: The National Surgical Quality Improvement Program database was used to identify patients undergoing hepatectomy between January 1 and December 31, 2014. Propensity score matching algorithm was used to balance differences in baseline characteristics among MIS and O-LR groups. RESULTS: A total of 3064 patients were included in the study. After propensity matching, the baseline characteristics for O-LR and MIS groups were comparable (minimum p value = 0.12). Incidence of superficial surgical site infections, intraoperative or postoperative blood transfusions, and pulmonary embolism was lower among patients in MIS group compared to O-LR (p < 0.02). Liver failure and biliary leakage were also less frequent among patients undergoing MIS (p < 0.01). Similarly, MIS was associated with a shorter length of hospital stay (LOS) compared to O-LR (p < 0.001). Of note, 30-day postoperative mortality and readmission were comparable between the two groups. CONCLUSIONS: Patients undergoing MIS had a lower postoperative morbidity and shorter LOS compared with patients undergoing O-LR. MIS is safe and may be associated with improved short-term outcomes following hepatic surgery. PMID- 27412323 TI - Modulating cell adhesion to polybutylene succinate biotextile constructs for tissue engineering applications. AB - Textile-based technologies are powerful routes for the production of three dimensional porous architectures for tissue engineering applications because of their feasibility and possibility for scaling-up. Herein, the use of knitting technology to produce polybutylene succinate fibre-based porous architectures is described. Furthermore, different treatments have been applied to functionalize the surface of the scaffolds developed: sodium hydroxide etching, ultraviolet radiation exposure in an ozone atmosphere and grafting (acrylic acid, vinyl phosphonic acid and vinyl sulphonic acid) after oxygen plasma activation as a way to tailor cell adhesion. A possible effect of the applied treatments on the bulk properties of the textile scaffolds has been considered and thus tensile tests in dry and hydrated states were also carried out. The microscopy results indicated that the surface morphology and roughness were affected by the applied treatments. The X-ray photoelectron spectroscopy and contact angle measurements showed the incorporation of oxygen-containing groups and higher surface free energy as result of the surface treatments applied. The DNA quantification and scanning electron microscopy analysis revealed that these modifications enhanced cell adhesion and altered cell morphology. Generally, sodium hydroxide treatment altered most significantly the surface properties, which in turn resulted in a high number of cells adherent to these surfaces. Based on the results obtained, the proposed surface treatments are appropriate to modify polybutylene succinate knitting scaffolds, influencing cell adhesion and its potential for use in tissue engineering applications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27412324 TI - High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma. AB - In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naive PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921). PMID- 27412327 TI - Autobiography of Piergiorgio Casavecchia: Forty Years of Happily Crossing Beams. PMID- 27412326 TI - Tribute to Piergiorgio Casavecchia and Antonio Lagana. PMID- 27412329 TI - Abbreviated Curriculum Vitae of Piergiorgio Casavecchia. PMID- 27412325 TI - Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein. AB - TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment. PMID- 27412328 TI - Colleagues of Piergiorgio Casavecchia. PMID- 27412330 TI - Hundred Most Significant Publications of Piergiorgio Casavecchia. PMID- 27412332 TI - Collaborators of Antonio Lagana. PMID- 27412331 TI - Autobiography of Antonio Lagana: Toward the Design of a European Integrated Collaborative Distributed Research Infrastructure for the Study of Molecular Processes. PMID- 27412333 TI - Curriculum Vitae of Antonia Lagana. PMID- 27412334 TI - Hundred Most Significant Publications of Antonio Lagana. PMID- 27412335 TI - Aero-Thermo-Dynamic Mass Analysis. AB - Each gas molecule has its own molecular weight, while such a microscopic characteristic is generally inaccessible, and thus, it is measured indirectly through e.g. ionization in conventional mass analysis. Here, we present a novel approach to the direct measurement of molecular weight through a nanoarchitectonic combination of aerodynamics, thermodynamics, and mechanics, transducing microscopic events into macroscopic phenomena. It is confirmed that this approach can provide molecular weight of virtually any gas or vaporizable liquid sample in real-time without ionization. Demonstrations through analytical calculations, numerical simulations, and experiments verify the validity and versatility of the novel mass analysis realized by a simple setup with a flexible object (e.g. with a bare cantilever and even with a business card) placed in a laminar jet. Owing to its unique and simple working principle, this aero-thermo dynamic mass analysis (AMA) can be integrated into various analytical devices, production lines, and consumer mobile platforms, opening new chapters in aerodynamics, thermodynamics, mechanics, and mass analysis. PMID- 27412336 TI - Panacibacter ginsenosidivorans gen. nov., sp. nov., with ginsenoside converting activity isolated from soil of a ginseng field. AB - A ginsenoside-transforming bacterium, designated Gsoil 1550T, was isolated from soil of a ginseng field and subjected to a polyphasic taxonomic analysis. Colonies of strain Gsoil 1550T were yellow, of low convexity and with regular margin. Cells were long rods, 0.5-1.2 um wide and 1.6-3 um long. The isolate grew at 10-37 degrees C and at pH 5-9 on R2A agar medium; maximum growth occurred at 30 degrees C and pH 6-7. Phylogenetic study based on the 16S rRNA gene sequence positioned Gsoil 1550T in a distinct lineage in the family Chitinophagaceae, sharing 92.5-92.8 % sequence similarity with members of the closely related genera Terrimonas, Parafilimonas, Sediminibacterium and Parasegetibacter. Strain Gsoil 1550T contained menaquinone MK-7 as the predominant quinone, and iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 0 and iso-C15 : 1 G as major fatty acids. The DNA G+C content was 44.6 mol%. Strain Gsoil 1550T could be distinguished from other members of the family Chitinophagaceae by a number of chemotaxonomic and phenotypic characteristics. The major polar lipid of strain Gsoil 1550T was phosphatidylethanolamine. Based on this polyphasic taxonomic analysis, strain Gsoil 1150T represents a novel species within a new genus, for which the name Panacibacter ginsenosidivorans gen. nov., sp. nov. is proposed. The type strain of Panacibacter ginsenosidivorans is Gsoil 1550T (=KCTC 12658T=JCM 31452T). PMID- 27412337 TI - Growing burden of sepsis-related mortality in northeastern Italy: a multiple causes of death analysis. AB - BACKGROUND: Few population-based data are available on mortality due to sepsis. The aim of the study was to estimate sepsis-related mortality rates and to assess the associated comorbidities. METHODS: From multiple causes of death data (MCOD) of the Veneto Region (northeastern Italy), all deaths with sepsis mentioned anywhere in the death certificate were retrieved for the period 2008-2013. Among these deaths the prevalence of common chronic comorbidities was investigated, as well as the distribution of the underlying cause of death (UCOD), the single disease selected from all condition mentioned in the certificate and usually tabulated in mortality statistics. Age-standardized mortality rates were computed for sepsis selected as the UCOD, and for sepsis mentioned anywhere in the certificate. RESULTS: Overall 16,906 sepsis-related deaths were tracked. Sepsis was mentioned in 6.3 % of all regional deaths, increasing from 4.9 in 2008 to 7.7 % in 2013. Sepsis was the UCOD in 0.6 % of total deaths in 2008, and in 1.6 % in 2013. Age-standardized mortality rates increased by 45 % for all sepsis-related deaths, and by 140 % for sepsis as the UCOD. Sepsis was often reported in the presence of chronic comorbidities, especially neoplasms, diabetes, circulatory diseases, and dementia. Respiratory tract and intra-abdominal infections were the most frequently associated sites of infection. CONCLUSIONS: MCOD analyses provide an estimate of the burden of sepsis-related mortality. MCOD data suggest an increasing importance attributed to sepsis by certifying physicians, but also a real increase in mortality rates, thus confirming trends reported in some other countries by analyses of hospital discharge records. PMID- 27412338 TI - Effects of Elevated In Ovo Selenium Exposure on Late Stage Development of Xenopus laevis Tadpoles. AB - The effects of elevated in ovo selenium (Se) exposure on late stage larval Xenopus laevis development were investigated. Adult females were fed diets augmented with selenomethionine for 68 days and bred with untreated males to obtain embryos with measured concentrations of 1.6 (control), 10.8, 28.1 and 81.7 MUg Se/g dry mass. Embryos were reared under uncontaminated conditions until 50 % of individuals within an aquarium had completed metamorphosis. The highest in ovo Se exposure group exhibited greater froglet body mass and snout to vent length while having a higher proportion of tadpoles at earlier stages of development. No differences were detected among treatment groups for mortality or metamorphic timing during the rearing period. This research suggests that in ovo Se exposure has minimal effect on the survival and development of late stage larval X. laevis in a controlled laboratory environment with adequate food availability. PMID- 27412340 TI - Remediation of Arsenic Contaminated Soil Using Phosphate and Colloidal Gas Aphron Suspensions Produced from Sapindus mukorossi. AB - Phosphate and colloidal gas aphrons (CGAs) generated from saponin extracted from Sapindus mukorossi fruit, were evaluated for washing low levels of arsenic from an iron rich soil. Phosphate is one of the most commonly dispersed chemicals that increases arsenic mobility in soil due to their structural similarities, making it an important factor in arsenic removal process. Column washing experiments were performed with CGAs in down flow and up flow modes on soil of pH 5 and 6. Soapnut CGAs, when paired with phosphate removed up to 95 % arsenic while soapnut CGAs alone could only remove up to 70 % arsenic. The presence of phosphate improved efficiency of soapnut solution by up to 35 %. SEM image of washed soil revealed minor corrosion of soil surface while using phosphate with soapnut. Therefore, the addition of phosphates would have positive impact on soil washing using soapnut saponin. PMID- 27412339 TI - Investigation of Total and Hexavalent Chromium in Filtered and Unfiltered Groundwater Samples at the Tucson International Airport Superfund Site. AB - Potential health effects from hexavalent chromium in groundwater have recently become a concern to regulators at the Tucson International Airport Area Superfund site. In 2016, the U.S. Geological Survey sampled 46 wells in the area to characterize the nature and extent of chromium in groundwater, to understand what proportion of total chromium is in the hexavalent state, and to determine if substantial differences are present between filtered and unfiltered chromium concentrations. Results indicate detectable chromium concentrations in all wells, over 75 % of total chromium is in the hexavalent state in a majority of wells, and filtered and unfiltered results differ substantially in only a few high turbidity total chromium samples. PMID- 27412341 TI - Contamination of the Alluvium of the Nitra River in Slovakia by Cadmium, Mercury and Lead as a Result of Previous Intense Industrial Activity. AB - The Nitra river is one of the most polluted rivers in the Slovak Republic. The aim of the study was to estimate the risk of Cd, Pb and Hg contamination of riverside sediments and alluvial soil in the vicinity of the Nitra river. The pseudototal Cd (all Cd forms except for residual fraction) and total Hg contents in riverside sediments (0.74-1.88 and 0.06-5.44 mg/kg, respectively) exceeded the limits for Cd and Hg in sandy soils (0.4 and 0.15 mg/kg). In three chosen localities in the flood plain of the Nitra river the soil content of mobile Pb forms (0.10-0.32 mg/kg), the pseudototal Cd (0.25-2.52 mg/kg) and total Hg content (0.03-1.6 mg/kg) exceeded the limits for Pb, Cd and Hg in loamy soils (0.1, 0.7 and 0.5 mg/kg, respectively). The obtained results confirmed the risk of Pb, Cd, Hg contamination caused by industrial activity in the vicinity of the Nitra river. PMID- 27412342 TI - Long-term support of patients receiving a left ventricular assist device for advanced heart failure: a follow-up analysis of the Registry to Evaluate the HeartWare Left Ventricular Assist System. AB - OBJECTIVES: The Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE) is an investigator-initiated multicentre, prospective, single-arm database established to collect post-Conformite Europeenne Mark clinical information on patients receiving the HeartWare(r) Ventricular Assist System (HVAD(r)). The number of patients requiring longer periods of mechanical circulatory support is ever increasing and so further investigation into long term outcomes in bridge-to-transplant populations is necessary. METHODS: Data were collected on 254 commercial implants performed between February 2009 and March 2012 from nine centres in Europe (7 centres) and Australia (2 centres). Patients were followed to device explant, heart transplant or death, and the outcomes of patients who remained on support longer than 2 years were analysed. Summary statistics were used to describe patient demographics, adverse events, length of support and outcomes for this long-term cohort. RESULTS: A total of 124 patients (49% of the original ReVOLVE population) were on support for more than 2 years (range: 731-2108 days), 76 of whom are still alive on support. Overall survival through 5 years was 59%. CONCLUSIONS: Owing to the low rate of heart transplants, a significant number of patients receiving a left ventricular assist device as a bridge to transplant remain on support for prolonged periods, often exceeding 2, 3 and even 4 years. Real-world use of the HVAD system continues to show excellent outcomes for patients on the device, including those on support beyond 2 years. PMID- 27412343 TI - Subannular perforation of left ventricular outflow tract associated with transcatheter valve implantation: pathophysiological background and clinical implications. AB - OBJECTIVES: Perforation of the subannular left ventricular outflow tract (LVOT) represents an uncommon but almost invariably fatal transcatheter aortic valve implantation (TAVI)-associated complication. The risk factors to predict the occurrence of this devastating complication, particularly in relation to specific LVOT anatomy, have not yet been systematically analysed. We aimed to evaluate the pathophysiological background and possible risk factors for the occurrence of subannular LVOT perforation. METHODS: A total of 6 (0.7%) consecutive patients (78.8 +/- 3.3 years, 83% women) with subannular LVOT perforation complicating TAVI procedure were identified from our institutional TAVI registry, including 900 consecutive patients who underwent TAVI procedure at a single institution between January 2009 and July 2015. Only patients with an intraoperatively confirmed LVOT perforation were included. RESULTS: The computed tomography (CT) guided analysis of aortic root/LVOT morphology revealed subannular calcification in close proximity of the anatomically weakest region of muscular LVOT (i.e. in the region of the muscular LVOT between the left fibrous trigone and the left/right commissure) in 5/6 (83%) patients. Moreover, significant annular asymmetry >20% was present in 4/6 (67%) patients and was combined with a severe asymmetric hypertrophy of muscular LVOT. CONCLUSIONS: Subannular calcification in close proximity of the anatomically unprotected muscular LVOT might represent an important risk factor for the occurrence of subannular LVOT injury. Precise CT based analysis of patient-specific aortic root anatomy/subannular calcification patterns may be helpful to predict this TAVI-associated complication preoperatively and hence to avoid it in future patients. PMID- 27412344 TI - Online sperm donation: a survey of the demographic characteristics, motivations, preferences and experiences of sperm donors on a connection website. AB - STUDY QUESTION: What are the demographic characteristics, motivations, preferences and experiences of heterosexual, gay and bisexual sperm donors on a connection website (i.e. a website that facilitates direct contact between donors and recipients of gametes)? SUMMARY ANSWER: This demographically diverse group of men was donating for altruistic reasons and perceived the website as providing greater choice over donation arrangements: approximately one third favoured anonymous donation, most of whom were heterosexual, whilst gay and bisexual donors were more likely to be in contact with children conceived with their sperm. WHAT IS KNOWN ALREADY: Despite substantially more sperm donors being registered on connection websites than with clinics, there has been very little research on this population. Current understanding of the impact of sexual orientation on donors' attitudes is also limited. STUDY DESIGN, SIZE, DURATION: An online survey was conducted over 7 weeks with 383 men registered as sperm donors with Pride Angel, a large UK-based connection website for donors and recipients of sperm. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey obtained data on participants' demographic characteristics and their motivations, preferences and experiences regarding online sperm donation, including attitudes towards contact with offspring. Differences according to participants' sexual orientation were examined. MAIN RESULTS AND THE ROLE OF CHANCE: Most participants (80.4%, 308) were heterosexual, 10.5% (40) were gay and 9.1% (35) were bisexual; ages ranged from 18 to 69 years (median = 36, mean = 37.3, SD = 9.7). A greater proportion of gay and bisexual men desired open-identity donation (P < 0.005) and contact with offspring (P <0.005) than heterosexual men. Approximately one third (28.7%, 110) had donated sperm; 18.3% (70) had conceived at least one child, of whom a minority (25.7%, 18) were currently in contact with the child, comprising significantly more gay and bisexual than heterosexual men (P = 0.001). Heterosexual men were most likely to state a preference for natural insemination, although the large majority (94.3%, 66) of donors who had conceived children had used artificial insemination. LIMITATIONS, REASONS FOR CAUTION: Findings may not be representative of all sperm donors using connection websites because members of only one website participated and participants were, by necessity, a self selected sample. WIDER IMPLICATIONS OF THE FINDINGS: This is the first comprehensive study of donors who connect with recipients via the internet, including a substantial number who have donated and conceived children. The findings indicate that sexual orientation may influence men's donation preferences and raise policy issues concerning donor recruitment and the incorporation of online sperm donation into clinical practice. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Wellcome Trust (097857/Z/11/Z). E.T. is the co-founder of Pride Angel; the remaining authors have no conflicts of interest. PMID- 27412345 TI - MMP-2 (-1306 C/T) Polymorphism Affects Serum Matrix Metalloproteinase (MMP)-2 Levels and Correlates with Chronic Obstructive Pulmonary Disease Severity: A Case Control Study of MMP-1 and -2 in a Tunisian Population. AB - OBJECTIVE: The aim of this study was to determine the role of MMP-1 (-1607 1G/2G; -519 A/G) and MMP-2 (-1306 C/T; -735 C/T) polymorphisms in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisian patients. We also evaluated the impact of these genetic variants on serum levels of the corresponding proteins. METHODS: The study included 138 patients with COPD and 216 healthy controls. Pulmonary function was evaluated using body plethysmography, and COPD severity was determined based on forced expiratory volume in 1 s (FEV1%). MMP-1 and MMP-2 variants were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while serum matrix metalloproteinase (MMP)-1 and -2 levels were determined by enzyme-linked immunosorbent assay (ELISA) and activity of MMP-2 was determined by gelatin zymography. RESULTS: No significant associations were found between genetic variations in MMP-1 and MMP-2 variants and the risk of development of COPD. Additionally, no significant impact of the MMP-1 (-1607 1G/2G; -519 A/G) and MMP 2 (-735 C/T) polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, a significant correlation was identified between the MMP-2 (-1306) C/T and disease severity [p = 0.01; Bonferroni corrected p value (p c) = 0.04]. Increased levels of MMP-2 were also identified in patients with the MMP-2 (-1306) CC genotype compared with those with CT and TT genotypes (105 [84.69-121.5] vs. 86.29 [80.99-92.62] ng/ml; p = 0.01, p c = 0.04). Additionally, MMP-2 activity was enhanced in patients carrying the CC genotype compared with those carrying the T variant (p = 0.01, p c = 0.02). CONCLUSION: Our data suggest that, although MMP-1 (-1607 1G/2G; -519 A/G) and MMP-2 (-735 C/T) may not affect COPD risk and clinical parameters, the MMP-2 (-1306C/T) variant was correlated to COPD severity. These findings could be related to alterations in the level and activity of MMP-2 in serum from patients carrying the (-1306) CC genotype. PMID- 27412346 TI - Differential cytotoxicity induced by the Titanium(IV)Salan complex Tc52 in G2 phase independent of DNA damage. AB - BACKGROUND: Chemotherapy is one of the major treatment modalities for cancer. Metal-based compounds such as derivatives of cisplatin are in the front line of therapy against a subset of cancers, but their use is restricted by severe side effects and the induction of resistance in treated tumors. Subsequent research focused on development of cytotoxic metal-complexes without cross-resistance to cisplatin and reduced side-effects. This led to the discovery of first-generation titanium(IV)salan complexes, which reached clinical trials but lacked efficacy. New-generation titanium (IV)salan-complexes show promising anti-tumor activity in mice, but their molecular mechanism of cytotoxicity is completely unknown. METHODS: Four different human cell lines were analyzed in their responses to a toxic (Tc52) and a structurally highly related but non-toxic (Tc53) titanium(IV)salan complex. Viability assays were used to reveal a suitable treatment range, flow-cytometry analysis was performed to monitor the impact of dosage and treatment time on cell-cycle distribution and cell death. Potential DNA strand break induction and crosslinking was investigated by immunostaining of damage markers as well as automated fluorometric analysis of DNA unwinding. Changes in nuclear morphology were analyzed by DAPI staining. Acidic beta galactosidase activity together with morphological changes was monitored to detect cellular senescence. Western blotting was used to analyze induction of pro apoptotic markers such as activated caspase7 and cleavage of PARP1, and general stress kinase p38. RESULTS: Here we show that the titanium(IV)salan Tc52 is effective in inducing cell death in the lower micromolar range. Surprisingly, Tc52 does not target DNA contrary to expectations deduced from the reported activity of other titanium complexes. Instead, Tc52 application interferes with progression from G2-phase into mitosis and induces apoptotic cell death in tested tumor cells. Contrarily, human fibroblasts undergo senescence in a time and dose dependent manner. As deduced from fluorescence studies, the potential cellular target seems to be the cytoskeleton. CONCLUSIONS: In summary, we could demonstrate in four different human cell lines that tumor cells were specifically killed without induction of major cytotoxicity in non-tumorigenic cells. Absence of DNA damaging activity and the cell-cycle block in G2 instead of mitosis makes Tc52 an attractive compound for further investigations in cancer treatment. PMID- 27412347 TI - Burden of asthma with elevated blood eosinophil levels. AB - BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD 9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (>=400 cells/MUL) and normal eosinophil level (<400 cells/MUL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76 14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma. PMID- 27412349 TI - From near hard spheres to colloidal surfboards. AB - This work revisits the synthesis of the colloidal particles most commonly used for making model near hard suspensions or as building blocks of model colloidal gels, i.e. sterically stabilised poly(methyl methacrylate) (PMMA) particles. The synthesis of these particles is notoriously hard to control and generally the problems are ascribed to the difficulty in synthesising the graft stabiliser (PMMA-g-PHSA). In the present work, it is shown that for improving the reliability of the synthesis as a whole, control over the polycondensation of the 12-polyhydroxystearic acid is the key. By changing the catalyst and performing the polycondensation in the melt, the chain length of the 12-polyhydroxystearic acid is better controlled, as confirmed by 1H-NMR spectroscopy. Control over the graft copolymer now enables us to make small variations of near hard sphere colloids, for example spherical PMMA particles with essentially the same core size and different stabilising layer thicknesses can now be readily produced, imparting controlled particle softness. The PMMA spheres can be further employed to create, in gram scale quantities, colloidal building blocks having geometrical and/or chemical anisotropy by using a range of mechanical deformation methods. The versatility of the latter methods is demonstrated for polystyrene latex particles as well. PMID- 27412348 TI - Whole-genome transcription and DNA methylation analysis of peripheral blood mononuclear cells identified aberrant gene regulation pathways in systemic lupus erythematosus. AB - BACKGROUND: Recent achievement in genetics and epigenetics has led to the exploration of the pathogenesis of systemic lupus erythematosus (SLE). Identification of differentially expressed genes and their regulatory mechanism(s) at whole-genome level will provide a comprehensive understanding of the development of SLE and its devastating complications, lupus nephritis (LN). METHODS: We performed whole-genome transcription and DNA methylation analysis in PBMC of 30 SLE patients, including 15 with LN (SLE LN(+)) and 15 without LN (SLE LN(-)), and 25 normal controls (NC) using HumanHT-12 Beadchips and Illumina Human Methy450 chips. The serum proinflammatory cytokines were quantified using Bio plex Human Cytokine 27-plex assay. Differentially expressed genes and differentially methylated CpG were analyzed with GenomeStudio, R, and SAM software. The association between DNA methylation and gene expression were tested. Gene interaction pathways of the differentially expressed genes were analyzed by IPA software. RESULTS: We identified 552 upregulated genes and 550 downregulated genes in PBMC of SLE. Integration of DNA methylation and gene expression profiling showed that 334 upregulated genes were hypomethylated, and 479 downregulated genes were hypermethylated. Pathway analysis on the differential genes in SLE revealed significant enrichment in interferon (IFN) signaling and toll-like receptor (TLR) signaling pathways. Nine IFN- and seven TLR-related genes were identified and displayed step-wise increase in SLE LN(-) and SLE LN(+). Hypomethylated CpG sites were detected on these genes. The gene expressions for MX1, GPR84, and E2F2 were increased in SLE LN(+) as compared to SLE LN(-) patients. The serum levels of inflammatory cytokines, including IL17A, IP-10, bFGF, TNF-alpha, IL-6, IL-15, GM-CSF, IL-1RA, IL-5, and IL-12p70, were significantly elevated in SLE compared with NC. The levels of IL-15 and IL1RA correlated with their mRNA expression. The upregulation of IL-15 may be regulated by hypomethylated CpG sites in the promotor region of the gene. CONCLUSIONS: Our study has demonstrated that significant number of differential genes in SLE were involved in IFN, TLR signaling pathways, and inflammatory cytokines. The enrichment of differential genes has been associated with aberrant DNA methylation, which may be relevant to the pathogenesis of SLE. Our observations have laid the groundwork for further diagnostic and mechanistic studies of SLE and LN. PMID- 27412350 TI - Dexmedetomidine protects against lung ischemia-reperfusion injury by the PI3K/Akt/HIF-1alpha signaling pathway. AB - PURPOSE: To evaluate the role of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor 1alpha (HIF-1alpha) signaling pathway in the protection by dexmedetomidine against lung ischemia-reperfusion injury (IRI) in rats. METHODS: Forty-eight male Sprague-Dawley rats weighing 250-350 g were randomly divided into six groups (n = 8 each group): sham group, IRI group, low dose dexmedetomidine group (LD group), high-dose dexmedetomidine group (HD group), combined low-dose dexmedetomidine and LY294002 group (LDL group), and combined high-dose dexmedetomidine and LY294002 group (HDL group). A 30-min ischemia was induced by occluding the hilum of the left lung, followed by a 120 min reperfusion by removing occlusion of the hilum. After the left lung was removed, the wet/dry weight ratio (W/D) of the lung tissues was determined. Pathological changes of lung tissues were evaluated by light and electron microscopes and the expression of p-Akt and HIF-1alpha in the lung tissues was determined by western blotting. RESULTS: Compared with the sham group, both the W/D ratio and lung injury were significantly increased, the p-Akt expression was down-regulated and HIF-1alpha expression was up-regulated in the five experimental groups. Compared with the LD and LDL groups, both the W/D ratio and lung injury were decreased, but the expression of p-Akt and HIF-1alpha was increased in the HD and HDL groups. CONCLUSIONS: Administration of dexmedetomidine before ischemia can provide a protection against lung IRI by re installing the PI3K/Akt/HIF-1alpha signaling pathway. PMID- 27412351 TI - Role of isopentenyl-diphosphate isomerase in heterologous cyanobacterial (Synechocystis) isoprene production. AB - Heterologous production of isoprene (C5H8) hydrocarbons in cyanobacteria, emanating from sunlight, CO2, and water, is now attracting increasing attention. The concept entails application of an isoprene synthase transgene from terrestrial plants, heterologously expressed in cyanobacteria, aiming to reprogram carbon flux in the terpenoid biosynthetic pathway toward formation and spontaneous release of this volatile chemical from the cell and liquid culture. However, flux manipulations and carbon-partitioning reactions between isoprene (the product) and native terpenoid biosynthesis for cellular needs are not yet optimized for isoprene yield. The primary reactant for isoprene biosynthesis is dimethylallyl diphosphate (DMAPP), whereas both DMAPP and its isopentenyl diphosphate (IPP) isomer are needed for cellular terpenoid biosynthesis. The present work addressed the function of an isopentenyl diphosphate (IPP) isomerase in cyanobacteria and its role in carbon partitioning between IPP and DMAPP, both of which serve, in variable ratios, as reactants for the synthesis of different cellular terpenoids. The work was approached upon the heterologous expression in Synechocystis of the "isopentenyl diphosphate isomerase" gene (FNI) from Streptococcus pneumoniae, using isoprene production as a "reporter process" for substrate partitioning between DMAPP and IPP. It is shown that transgenic expression of the FNI gene in Synechocystis resulted in a 250 % increase in the "reporter isoprene" rate and yield, suggesting that the FNI isomerase shifted the endogenous DMAPP-IPP steady-state pool size toward DMAPP, thereby enhancing rates and yield of isoprene production. The work provides insight into the significance and functional role of the IPP isomerase in these photosynthetic microorganisms. PMID- 27412352 TI - (1) H NMR-Guided Isolation of Formyl-Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta. AB - Nine formyl-phloroglucinolmeroterpenoids (FPMs), namely, eucalrobusones A-I (1 9), were isolated from the leaves of Eucalyptus robusta by tracking the phenolic hydroxyl (1) H NMR peaks. The Snatzke helicity rules for the Cotton effects of twisted benzene rings were applied to elucidate the absolute configurations of the FPMs. These findings, along with NMR spectroscopy, the circular dichroism (CD) exciton chirality method, and CD calculations, allowed complete structures for the FPMs to be assigned. Eucalrobusones A-F (1-6) are novel adducts formed between a formyl-derived carbon atom on the phloroglucinol ring and monoterpene and sesquiterpene components. Eucalrobusones G-I (7-9) are the first examples of FPMs with cubebane part structures connected by an unusual 1 oxaspiro[5.5]undecane subunit. Among these isolates, eucalrobusone C (3) showed significant cytotoxicity against HepG2, MCF-7, and U2OS cancer cell lines, with IC50 values less than 10 MUm. Compound 3 significantly blocks cell proliferation in MCF-7 cells and induces MCF-7 cell death through apoptosis. PMID- 27412353 TI - The effects of aerobic exercise on the structure and function of DMN-related brain regions: a systematic review. AB - Physical activity may play a role in both the prevention and slowing of brain volume loss and may be beneficial in terms of improving the functional connectivity of brain regions. But much less is known about the potential benefit of aerobic exercise for the structure and function of the default mode network (DMN) brain regions. This systematic review examines the effects of aerobic exercise on the structure and function of DMN brain regions in human adulthood. Seven electronic databases were searched for prospective controlled studies published up to April 2015. The quality of the selected studies was evaluated with the Cochrane Collaboration's tool for assessing the risk of bias. RevMan 5.3 software was applied for data analysis. Finally, 14 studies with 631 participants were identified. Meta-analysis revealed that aerobic exercise could significantly increase right hippocampal volume (SMD = 0.26, 95% CI 0.01-0.51, p = 0.04, I2 = 7%, 4 studies), and trends of similar effects were observed in the total (SMD = 0.12, 95% CI -0.17 to 0.41, p = 0.43, I2 = 0%, 5 studies), left (SMD = 0.12, 95% CI -0.13 to 0.37, p = 0.33, I2 = 14%, 4 studies), left anterior (SMD = 0.12, 95% CI -0.16 to 0.40, p = 0.41, I2 = 74%, 2 studies) and right anterior (SMD = 0.10, 95% CI -0.17 to 0.38, p = 0.46, I2 = 76%, 4 studies) hippocampal volumes compared to the no-exercise interventions. A few studies reported that relative to no exercise interventions, aerobic exercise could significantly decrease the atrophy of the medial temporal lobe, slow the anterior cingulate cortex (ACC) volume loss, increase functional connectivity within the hippocampus and improve signal activation in the cingulate gyrus and ACC. The current review suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex and the medial temporal areas of the DMN. Moreover, aerobic exercise may increase functional connectivity or activation in the hippocampus, cingulate cortex and parahippocampal gyrus regions of the DMN. However, considering the quantity and limitations of the included studies, the conclusion could not be drawn so far. Additional randomized controlled trials (RCTs) with rigorous designs and longer intervention periods are needed in the future. PMID- 27412354 TI - Knowledge, attitudes, beliefs, values, preferences, and feasibility in relation to the use of injection safety devices in healthcare settings: a systematic review. AB - BACKGROUND: Adopting technologies such as injection safety devices in healthcare settings can enhance injection safety. Developing guidelines for appropriate adoption of such technologies need to consider factors beyond evidence for their health effects. The objective of this study is to systematically review the published literature for evidence among healthcare workers and patients about knowledge, attitudes, beliefs, values, preferences, and feasibility in relation to the use of injection safety devices in healthcare settings. METHODS: We included both qualitative and quantitative studies conducted with the general public, patients, and healthcare workers, administrators, or policy makers. We searched MEDLINE, EMBASE, CINHAL and CENTRAL. We used a duplicate and independent approach to title and abstract screening, full text screening, data abstraction and risk of bias assessment. RESULTS: Out of a total of 6568 identified citations, we judged fourteen studies as eligible for this systematic review. All these studies were surveys, conducted with healthcare workers in high-income countries. We did not identify any qualitative study, or a study of the general public, patients, healthcare administrators or policy makers. We did not identify any study assessing knowledge, or values assigned to outcomes relevant to injection safety devices. Each of the included studies suffered from methodological limitations, which lowers our confidence in their findings. Based on the findings of six studies, the injection safety devices were generally perceived as easy to use and as an improvement compared with conventional syringes. Some of these studies reported few technical problems while using the devices. In three studies assessing perceived safety, the majority of participants judged the devices as safe. Two studies reported positive perceptions of healthcare workers regarding patient tolerance of these injection safety devices. One study found that less than half the nurses felt comfortable using the insulin pens. Findings from four studies assessing preference and satisfaction were not consistent. CONCLUSIONS: This systematic review identified evidence that injection safety devices are generally perceived as easy to use, safe, and tolerated by patients. There were few reports of technical problems while using the devices and some discomfort by nurses using the insulin pens. PMID- 27412355 TI - Thermally robust and biomolecule-friendly room-temperature bonding for the fabrication of elastomer-plastic hybrid microdevices. AB - Here, we introduce a simple and fast method for bonding a poly(dimethylsiloxane) (PDMS) silicone elastomer to different plastics. In this technique, surface modification and subsequent bonding processes are performed at room temperature. Furthermore, only one chemical is needed, and no surface oxidation step is necessary prior to bonding. This bonding method is particularly suitable for encapsulating biomolecules that are sensitive to external stimuli, such as heat or plasma treatment, and for embedding fracturable materials prior to the bonding step. Microchannel-fabricated PDMS was first oxidized by plasma treatment and reacted with aminosilane by forming strong siloxane bonds (Si-O-Si) at room temperature. Without the surface oxidation of the amine-terminated PDMS and plastic, the two heterogeneous substrates were brought into intimate physical contact and left at room temperature. Subsequently, aminolysis occurred, leading to the generation of a permanent seal via the formation of robust urethane bonds after only 5 min of assembling. Using this method, large-area (10 * 10 cm) bonding was successfully realized. The surface was characterized by contact angle measurements and X-ray photoelectron spectroscopy (XPS) analyses, and the bonding strength was analyzed by performing peel, delamination, leak, and burst tests. The bond strength of the PDMS-polycarbonate (PC) assembly was approximately 409 +/- 6.6 kPa, and the assembly withstood the injection of a tremendous amount of liquid with the per-minute injection volume exceeding 2000 times its total internal volume. The thermal stability of the bonded microdevice was confirmed by performing a chamber-type multiplex polymerase chain reaction (PCR) of two major foodborne pathogens - Escherichia coli O157:H7 and Salmonella typhimurium - and assessing the possibility for on-site direct detection of PCR amplicons. This bonding method demonstrated high potential for the stable construction of closed microfluidic systems socketed with biomolecule-immobilized surfaces such as DNA, antibody, enzyme, peptide, and protein microarrays. PMID- 27412356 TI - Rapid species identification and epidemiological analysis of carbapenem-resistant Acinetobacter spp. by a PCR-based open reading frame typing method. AB - The spread of carbapenem-resistant Acinetobacter spp. has become a global problem. In this study, 18 carbapenem-resistant Acinetobacter calcoaceticus baumannii (ACB) complexes, identified using a conventional biochemical method at our hospital during 2004-2013, were studied for species identification and epidemiological analyses. Species identification was performed using matrix assisted laser desorption ionization-time-of-flight MS, a partial sequence analysis of rpoB and a PCR-based ORF typing (POT) method. The POT method can not only identify the species of ACB complexes but also simultaneously determine the international epidemic clones and the genetic identities of Acinetobacterbaumannii in several hours. Carbapenem resistance gene detection by PCR, molecular epidemiological analysis by PFGE and Pasteur Institute multilocus sequence typing (MLST) analysis were performed. All three methods identified 18 isolates as A. baumannii (n=10), Acinetobacterpittii (n=4) and Acinetobacternosocomialis (n=4). A metallo-beta-lactamase gene in all strains of A. pittii and A. nosocomialis and an ISAba1 gene in the upstream of the blaOXA-51 like gene in eight strains of A. baumannii were detected, respectively, as carbapenemase-related genes. Results from PFGE demonstrated that nine strains of A. baumannii were closely related genetically. Results of MLST analysis showed that A. baumannii are classifiable to sequence type 2. These results were consistent with those obtained using the POT method. This POT method can easily and rapidly identify the international epidemic clones and the identities of A. baumannii. It can be a useful tool for infection control. PMID- 27412357 TI - Adrenocortical carcinoma surgery-surgical extent and approach. AB - PURPOSE: Adequate tumour resection is the gold standard of care for adrenocortical carcinoma (ACC). However, the optimal surgical strategy remains debatable. In our opinion, the extent of surgery (adequate tumour resection) is the primary concern, rather than the surgical approach (laparoscopic or open). We propose that both surgical approaches have a role in the management of ACC provided the extent of resection is selected based on patient and tumour characteristics and accurate pre-operative investigations. METHODS: A review of 25 curative intent resections for ACC between 2002 and 2013 was done. Group A (16 patients-64 %) included all patients who underwent planned radical adrenalectomy without any other resection and group B (9 patients-36 %) included all patients who underwent a planned extensive resection based on pre-operative investigations. RESULTS: Of 471 adrenalectomies, 25 were performed for ACC with curative intent. Tumours were significantly larger in group B with mean size of 119.6 versus 62.4 mm in group A (p = 0.002). Tumours in group B also had higher WEISS scores (mean score 7 vs 5.2, p = 0.033) and almost always required multi organ resection. The recurrence rate was 37.5 % (n = 6) for group A and 44.4 % for group B (n = 4), p = 1.00. Poor prognosis was associated with significantly higher WEISS scores (p = 0.016) and a trend towards more advanced ENSAT disease stage (p = 0.06). Estimated overall survival was 74.17 months (group A 67.3 vs group B 70.1, p = 0.244). CONCLUSIONS: Accurate pre-operative staging is critical to select a tailored surgical strategy. Multi-organ resection remains the preferred approach for large and potentially invasive ACC. Some patients presenting with smaller ACC may benefit from a more extensive resection. PMID- 27412358 TI - Fibroblast growth factors: new insights, new targets in the management of diabetes. AB - The fibroblast growth factor (FGF) family consists of 22 evolutionarily and structurally related proteins (FGF1 to FGF23; with FGF15 being the rodent ortholog of human FGF19). Based on their mechanism of action, FGFs can be categorized into intracrine, autocrine/paracrine and endocrine subgroups. Both autocrine/paracrine and endocrine FGFs are secreted from their cells of origin and exert their effects on target cells by binding to and activating specific single-pass transmembrane tyrosine kinase receptors (FGFRs). Moreover, FGF binding to FGFRs requires specific cofactors, namely heparin/heparan sulfate proteoglycans or Klothos for autocrine/paracrine and endocrine FGF signaling, respectively. FGFs are vital for embryonic development and mediate a broad spectrum of biological functions, ranging from cellular excitability to angiogenesis and tissue regeneration. Over the past decade certain FGFs (e.g. FGF1, FGF10, FGF15/FGF19 and FGF21) have been further recognized as regulators of energy homeostasis, metabolism and adipogenesis, constituting novel therapeutic targets for obesity and obesity-related cardiometabolic disease. Until recently, translational research has been mainly focused on FGF21, due to the pleiotropic, beneficial metabolic actions and the relatively benign safety profile of its engineered variants. However, increasing evidence regarding the role of additional FGFs in the regulation of metabolic homeostasis and recent developments regarding novel, engineered FGF variants have revitalized the research interest into the therapeutic potential of certain additional FGFs (e.g. FGF1 and FGF15/FGF19). This review presents a brief overview of the FGF family, describing the mode of action of the different FGFs subgroups, and focuses on FGF1 and FGF15/FGF19, which appear to also represent promising new targets for the treatment of obesity and type 2 diabetes. PMID- 27412359 TI - Medical causes of temporary or definitive leaves from a French counterterrorist unit pre-internship. AB - INTRODUCTION: Each year, the French Special Weapons And Tactics team, Groupe d'Intervention de la Gendarmerie Nationale, recruits new members through a physically demanding 8-week selection process. The goal of this study is to estimate the incidence and the causes for temporary or final interruptions during this process for medical reasons. SUBJECTS, MATERIAL AND METHODS: All of the candidates for the November 2015 selection process were included in this prospective study. The number and reasons for temporary or final interruptions were documented by military general practitioners. RESULTS: The applicants were 48 law enforcement professionals (2 women, mean age 29.4 years, range 22-35). In 14 cases, a temporary interruption was required and in five cases the selection process prematurely ended. Fifty-two per cent of the temporary interruptions were due to sprains, tendinopathies, fractures or muscle tears, 11% were due to burns, wounds or subcutaneous bruises, 16% were due to cranial trauma and 21% were due to medical causes. DISCUSSION: The high prevalence of minor traumatology that we observed is similar to the ones observed in other cohorts describing initial training for military personnel in the conventional forces. However, the presence of other pathologies in our study, such as cranial trauma or medical causes, is due to the specificity of this internship selection granting access to an elite unit. PMID- 27412360 TI - Lessons learned from early rehabilitation of complex trauma at the Royal Centre for Defence Medicine. AB - During the recent conflicts in Iraq and Afghanistan, substantial numbers of service personnel survived devastating injuries, presenting significant challenges for early rehabilitation at Queen Elizabeth Hospital Birmingham. Royal Centre for Defence Medicine personnel augmented NHS therapy provision, gaining significant experience in rehabilitating complex trauma. Multidisciplinary working was key to delivering this service, with a unique rehabilitation coordinating officer position established to manage the rehabilitation pathway. A military exercise rehabilitation instructor provided daily gym-based rehabilitation, developing exercise tolerance. Emphasis was placed on early independence, reducing pain, eliminating complications and optimising function. Innovative solutions and non-standard combinations of rehabilitation were required, with therapy working practices redesigned that, we believe, exceed provision elsewhere, including novel applications such as unique patient transfers, specialist seating, additional equipment, problem-solving teaching and early upper limb prosthetic provision. Active pain management allowed engagement in rehabilitation. With limited evidence available, therapeutic modalities attempting to alleviate phantom limb pain centred on patients' ability to engage in treatment. Finally, the requirement to measure change in early trauma rehabilitation was identified, leading to the development of the preprosthetic functional outcome measure. This article aims to document advances made, lessons learned, encourage debate and identify priorities for future research for military complex trauma rehabilitation. PMID- 27412361 TI - The impact of cash transfers on social determinants of health and health inequalities in Sub-Saharan Africa: a systematic review protocol. AB - BACKGROUND: There is increasing pressure to address the social determinants of health (SDoH) and health inequities through the implementation of culturally acceptable interventions particularly in Sub-Saharan Africa (SSA) where health outcomes are generally poor. Available evaluation research on cash transfers (CTs) suggests that the programs may influence the wider determinants of health in SSA; yet, there has been no attempt to synthesize the evidence regarding their contribution to tackling the SDoH and health inequalities. To date, nearly all the reviews on CTs' impact on health have predominantly featured evidence from Latin America with limited transferability to the social, cultural, and political environments in SSA. Therefore, the aim of this study is to undertake a systematic review to assess the role of CTs in tackling the wider determinants of health and health inequalities in SSA. METHODS/DESIGN: A systematic review of published and unpublished literature on CTs' impact on health and health determinants covering the period 2000-2016 will be undertaken. Studies will be considered for inclusion if they present quantitative or qualitative data, including all relevant study designs. The SDoH conceptual framework will be used to guide the data extraction process. EPPI Reviewer software will be used for data management and analysis. Studies included in the review will be analyzed by narrative synthesis and/or meta-analysis as appropriate for the nature of the data retrieved. DISCUSSION: This review will provide empirical evidence on the impact of CTs on SDoH to inform CT policy, implementation, and research in SSA. The protocol follows the Preferred Reporting Items for Systematic Review and Meta Analysis Protocols (PRISMA-P). SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered with the PROSPERO international prospective register of systematic reviews, reference CRD42015025015 . PMID- 27412362 TI - Oral non-steroidal anti-inflammatory drugs (single dose) for perineal pain in the early postpartum period. AB - BACKGROUND: Many women experience perineal pain after childbirth, especially after having sustained perineal trauma. Perineal pain-management strategies are thus an important part of postnatal care. Non-steroidal anti-inflammatory drugs (NSAIDs) are a commonly used type of medication in the management of postpartum pain and their effectiveness and safety should be assessed. OBJECTIVES: To determine the effectiveness of a single dose of an oral NSAID for relief of acute perineal pain in the early postpartum period. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016), OpenSIGLE, ProQuest Dissertations and Theses, the ISRCTN Registry and ClinicalTrials.gov (31 March 2016). We also reviewed reference lists of retrieved papers and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing a single dose of a NSAID versus a single dose of placebo, paracetamol or another NSAID for women with perineal pain in the early postpartum period. Quasi-RCTs and cross-over trials were excluded. DATA COLLECTION AND ANALYSIS: Two review authors (FW and VS) independently assessed all identified papers for inclusion and risk of bias. Any discrepancies were resolved through discussion and consensus. Data extraction, including calculations of pain relief scores, was also conducted independently by two review authors and checked for accuracy. MAIN RESULTS: We included 28 studies that examined 13 different NSAIDs and involved 4181 women (none of whom were breastfeeding). Studies were published between 1967 and 2013, with the majority published in the 1980s. Of the 4181 women involved in the studies, 2642 received a NSAID and 1539 received placebo or paracetamol. Risk of bias was generally unclear due to poor reporting, but in most studies the participants and personnel were blinded, outcome data were complete and the outcomes that were specified in the methods section were reported.None of the included studies reported on any of this review's secondary outcomes: prolonged hospitalisation or re-hospitalisation due to perineal pain; breastfeeding (fully or mixed) at discharge; breastfeeding (fully or mixed) at six weeks; perineal pain at six weeks; maternal views; postpartum depression; instrumental measures of disability due to perineal pain. NSAID versus placeboCompared to women who received a placebo, more women who received a single dose NSAID achieved adequate pain relief at four hours (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.64 to 2.23, 10 studies, 1573 participants (low-quality evidence)) and adequate pain relief at six hours (RR 1.92, 95% CI 1.69 to 2.17, 17 studies, 2079 participants (very low-quality evidence)). Women who received a NSAID were also less likely to need additional analgesia compared to women who received placebo at four hours (RR 0.39, 95% CI 0.26 to 0.58, four studies, 486 participants (low-quality evidence)) and at six hours after initial administration (RR 0.32, 95% CI 0.26 to 0.40, 10 studies, 1012 participants (low-quality evidence)). Fourteen maternal adverse effects were reported in the NSAID group (drowsiness (5), abdominal discomfort (2), weakness (1), dizziness (2), headache (2), moderate epigastralgia (1), not specified (1)) and eight in the placebo group (drowsiness (2), light headed (1), nausea (1), backache (1), dizziness (1), epigastric pain (1), not specified (1)), although not all studies assessed adverse effects. There was no difference in overall maternal adverse effects between NSAIDs and placebo at six hours post administration (RR 1.38, 95% CI 0.71 to 2.70, 13 studies, 1388 participants (very low-quality evidence)). One small study (with two treatment arms) assessed maternal adverse effects at four hours post-administration, but there were no maternal adverse effects observed (one study, 90 participants (low-quality evidence)). Neonatal adverse effects were not assessed in any of the included studies. NSAID versus paracetamolNSAIDs versus paracetamol were also more effective for adequate pain relief at four hours (RR 1.54, 95% CI 1.07 to 2.22, three studies, 342 participants) but not at six hours post-administration. There was no difference in the need for additional analgesia between the two groups at four hours (RR 0.55, 95% CI 0.27 to 1.13, one study, 73 participants), but women in the NSAID group were less likely to need any additional analgesia at six hours (RR 0.28, 95% CI 0.12 to 0.67, one study, 59 participants). No maternal adverse effects were reported four hours after drug administration (one study). Six hours post-administration, there was no difference between the groups in the number of maternal adverse effects (RR 0.74, 95% CI 0.27 to 2.08, three studies, 300 participants), with one case of pruritis in the NSAID group and one case of sleepiness in the paracetamol group. Neonatal adverse effects were not assessed in any of the included studies.Comparisons of different NSAIDs and different doses of the same NSAID did not demonstrate any differences in their effectiveness on any of the primary outcome measures; however, few data were available on some NSAIDs. AUTHORS' CONCLUSIONS: In women who are not breastfeeding and who sustained perineal trauma, NSAIDs (compared to placebo) provide greater pain relief for acute postpartum perineal pain and fewer women need additional analgesia when treated with a NSAID. However, the risk of bias was unclear for many of the included studies, adverse effects were often not assessed and breastfeeding women were not included in the studies. The overall quality of the evidence (GRADE) was low with the evidence for all outcomes rated as low or very low. The main reasons for downgrading were inclusion of studies with high risk of bias and inconsistency of findings of individual studies.NSAIDs also appear to be more effective in providing relief for perineal pain than paracetamol, but few studies were included in this analysis.Future studies should examine NSAIDs' adverse effects profile including neonatal adverse effects and the compatibility of NSAIDs with breastfeeding, and assess other important secondary outcomes of this review. Moreover, studies mostly included women who had episiotomies. Future research should consider women with and without perineal trauma, including perineal tears. High-quality studies should be conducted to further assess the efficacy of NSAIDs versus paracetamol and the efficacy of multimodal treatments. PMID- 27412363 TI - Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity. AB - Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form of the GTPase Cdc42 decreases dendritic branching. CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic branching. Thus, CALEB/NGC organizes a Rho GTPase signaling module at the plasma membrane for shaping dendritic trees. PMID- 27412364 TI - Thin film synthesis of SbSI micro-crystals for self-powered photodetectors with rapid time response. AB - We describe a new thin film deposition method for the growth of crystalline SbSI micro-needles via the conversion of Sb2S3 using SbI3 vapour, in a facile process that takes less than 15 minutes. These films were used to construct photodetectors in a sandwich-type architecture, which are superior to previously reported SbSI photodetectors. The devices exhibit a detectivity of D* = 10(9) Jones, a signal-to-noise ratio greater than SNR = 10(3) and a responsivity of R = 10(-5) A W(-1). In time response measurements, raise and fall times of less than 8 ms and 34 ms were determined. This manufacturing method greatly simplifies the creation of fast photodetectors. PMID- 27412365 TI - How Escherichia coli lands and forms cell clusters on a surface: a new role of surface topography. AB - Bacterial response to surface topography during biofilm formation was studied using 5 MUm tall line patterns of poly (dimethylsiloxane) (PDMS). Escherichia coli cells attached on top of protruding line patterns were found to align more perpendicularly to the orientation of line patterns when the pattern narrowed. Consistently, cell cluster formation per unit area on 5 MUm wide line patterns was reduced by 14-fold compared to flat PDMS. Contrasting the reduced colony formation, cells attached on narrow patterns were longer and had higher transcriptional activities, suggesting that such unfavorable topography may present a stress to attached cells. Results of mutant studies indicate that flagellar motility is involved in the observed preference in cell orientation on narrow patterns, which was corroborated by the changes in cell rotation pattern before settling on different surface topographies. These findings led to a set of new design principles for creating antifouling topographies, which was validated using 10 MUm tall hexagonal patterns. PMID- 27412366 TI - Pharmacokinetic Profile of Oral Magnesium Hydroxide. AB - Despite the presumption of a beneficial effect of magnesium (Mg) supplementation on various diseases, little is known concerning the pharmacokinetics of Mg hydroxide. This study was designed to provide a pharmacokinetic profile of Mg hydroxide after a single oral dose. Ten healthy male adults participated in this cross-over study with three 24-hr study days. Interventions were (i) none (baseline), (ii) oral intake of three (3 * 360 mg) tablets of Mg hydroxide (Mablet(r) ) and (iii) IV bolus infusion of 2 g Mg sulphate (index drug). Blood samples were collected before the single dose, after (i.e. after treatment administration) 15, 30, 60, 90 and 120 min. and after 3, 4, 6, 8, 12 and 24 hr. Urine was collected in four 6-hr periods per study day. Blood (N = 10) and urine (N = 6) Mg were analysed by descriptive statistics. Bioavailability was 14.9% (CI: 8.3; 26.8), blood clearance was 5.1 L/hr (CI: 2.1; 17.0), apparent volume of distribution was 60.2 L (CI: 35.6; 102.0), elimination constant was 0.08 per hour (CI: 0.05; 0.14), half-life was 8.3 hr (CI: 4.8; 14.1), Cmax was 0.11 mmol/L (CI: 0.07; 0.14), and AUC[0-24] was 92.3 mmol/L * min. (CI: 45.5; 139.1). Urine Mg excretion augmented by 17.7% (CI: 8.9; 35.0) from baseline. No severe side effects were observed. The bioavailability of Mg hydroxide was 15%, and it constitutes a clinically relevant option for oral Mg supplementation. No severe side effects were seen. PMID- 27412367 TI - Thermoelectric performance enhancement of Mg2Sn based solid solutions by band convergence and phonon scattering via Pb and Si/Ge substitution for Sn. AB - In this study, the thermoelectric properties of Mg2Sn0.98-xPbxSb0.02 were first studied, and then Mg2Sn0.93-xSixPb0.05Sb0.02 and Mg2Sn0.93-xGexPb0.05Sb0.02 were accordingly investigated. The results showed that the formation of Mg2Sn0.98 xPbxSb0.02 solid solutions effectively reduced the lattice thermal conductivity of Mg2Sn. The room temperature lattice thermal conductivity of Mg2Sn0.98Sb0.02 is ~5.2 W m(-1) K(-1) but only ~2.5 W m(-1) K(-1) for Mg2Sn0.73Pb0.25Sb0.02, a reduction of ~52%. Further alloying Mg2Sn0.98-xPbxSb0.02 with Mg2Si or Mg2Ge to form Mg2Sn0.93-xSixPb0.05Sb0.02 or Mg2Sn0.93-xGexPb0.05Sb0.02 reduced the lattice thermal conductivity significantly due to enhanced phonon scattering by point defects as well as nanoparticles. Moreover, bipolar thermal conductivities were suppressed due to the larger bandgap of Mg2Si and Mg2Ge than Mg2Sn. Furthermore, similar to the pseudo-binary Mg2Sn-Mg2Si and Mg2Sn-Mg2Ge systems, band convergence was also observed in pseudo-ternary Mg2Sn0.93-xSixPb0.05Sb0.02 and Mg2Sn0.93-xGexPb0.05Sb0.02 materials. The convergence of conduction bands led to higher PFs at lower temperatures for Mg2Sn0.93-xSixPb0.05Sb0.02 and Mg2Sn0.93 xGexPb0.05Sb0.02 materials. As a result, higher peak ZTs of ~1.3 for Mg2Sn0.63Si0.3Pb0.05Sb0.02 and ~1.2 for Mg2Sn0.68Ge0.25Pb0.05Sb0.02 were achieved. PMID- 27412368 TI - Association of prenatal and early life exposure to tetrachloroethylene (PCE) with polycystic ovary syndrome and other reproductive disorders in the cape cod health study: A retrospective cohort study. AB - BACKGROUND: Tetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage. METHODS: Five-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software. RESULTS: For any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5-1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders. CONCLUSION: No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders. PMID- 27412371 TI - Low nanomolar caffeic acid attenuates high glucose-induced endothelial dysfunction in primary human umbilical-vein endothelial cells by affecting NF kappaB and Nrf2 pathways. AB - Hyperglycemia contributes to dysregulate endothelial function associated with diabetes, leading to initiation and propagation of vascular complications and dysfunction. Caffeic acid (CA), a dietary hydroxycinnamic acid abundant in coffee, has been reported to exert antidiabetic effects in rat models. Herein, we investigated the molecular effects of physiological concentrations of CA (10 nM) against endothelial dysfunction induced by high glucose (HG) in human endothelial cells (HUVECs). HUVECs were exposed to HG 25 mM, to mimic diabetic condition, in presence of CA. Intracellular redox status (reduced glutathione, superoxide dismutase (SOD) and total antioxidant activity levels), and NF-kappaB pathway were examined. We also evaluated the involvement of NF-E2-related factor 2 (Nrf2)/electrophile responsive element (EpRE) pathway. Our data show that CA inhibits HG-induced nuclear translocation of NF-kappaB and the downstream expression of endothelial adhesion molecule 1 and restores antioxidant levels by upregulating Nrf2/EpRE pathway. Our data suggest that CA can suppress several aspects of HG-induced endothelial dysfunction through the modulation of intracellular redox status controlled by the transcription factor Nrf2. These findings highlight that low physiological concentration of CA achievable specifically upon food consumption are able to prevent endothelial dysfunction associated with inflammation and oxidative stress induced by high concentration of glucose. (c) 2016 BioFactors, 43(1):54-62, 2017. PMID- 27412372 TI - High-quality III-nitride films on conductive, transparent (201)-oriented beta Ga2O3 using a GaN buffer layer. AB - We demonstrate the high structural and optical properties of InxGa1-xN epilayers (0 <= x <= 23) grown on conductive and transparent (01)-oriented beta-Ga2O3 substrates using a low-temperature GaN buffer layer rather than AlN buffer layer, which enhances the quality and stability of the crystals compared to those grown on (100)-oriented beta-Ga2O3. Raman maps show that the 2" wafer is relaxed and uniform. Transmission electron microscopy (TEM) reveals that the dislocation density reduces considerably (~4.8 * 10(7) cm(-2)) at the grain centers. High resolution TEM analysis demonstrates that most dislocations emerge at an angle with respect to the c-axis, whereas dislocations of the opposite phase form a loop and annihilate each other. The dislocation behavior is due to irregular (01) beta-Ga2O3 surface at the interface and distorted buffer layer, followed by relaxed GaN epilayer. Photoluminescence results confirm high optical quality and time-resolved spectroscopy shows that the recombination is governed by bound excitons. We find that a low root-mean-square average (<=1.5 nm) of InxGa1-xN epilayers can be achieved with high optical quality of InxGa1-xN epilayers. We reveal that (01)-oriented beta-Ga2O3 substrate has a strong potential for use in large-scale high-quality vertical light emitting device design. PMID- 27412370 TI - Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate. AB - The L-iduronic acid (IdoA) residue is a critically important structural component in heparan sulphate polysaccharide for the biological functions. The pyranose ring of IdoA is present in (1)C4-chair, (2)SO-skew boat, and less frequently, in (4)C1-chair conformations. Here, we analyzed the conformation of IdoA residue in eight hexasaccharides by NMR. The data demonstrate a correlation between the conformation of IdoA and sulphations in the surrounding saccharide residues. For the 2-O-sulpho IdoA residue, a high degree of sulphation on neighboring residues drives ring dynamics towards the (2)SO-skew boat conformer. In contrast, the nonsulphated IdoA residue is pushed towards the (1)C4-chair conformer when the neighboring residues are highly sulphated. Our data suggest that the conformation of IdoA is regulated by the sulphation pattern of nearby saccharides that is genetically controlled by the heparan sulphate biosynthetic pathway. PMID- 27412369 TI - Maternal exposure to di-2-ethylhexylphthalate and adverse delivery outcomes: A systematic review. AB - Adverse pregnancy outcomes, including preterm delivery, short gestational age, and abnormal birth weight, remain a public health concern. The evidence on the association of the most common phthalate, di-2-ethylhexyl phthalate (DEHP) with adverse pregnancy outcomes remains equivocal. This systematic review summarizes published studies that investigated the association of DEHP with preterm delivery, gestational age, and birthweight. A comprehensive literature search found 15 relevant studies, most of which evaluated more than one outcome (four studies for preterm delivery, nine studies for gestational age, and ten studies for birthweight). Studies varied greatly with respect to study design, exposure assessment, analytical methods, and direction of the associations. We identified important methodological concerns which could have resulted in selection bias and exposure misclassification and contributed to null findings and biased associations. Given limitations of the previous studies discussed in this review, more thorough investigation of these associations is warranted to advance our scientific knowledge. PMID- 27412373 TI - Thermodynamic and redox properties of graphene oxides for lithium-ion battery applications: a first principles density functional theory modeling approach. AB - Understanding the thermodynamic stability and redox properties of oxygen functional groups on graphene is critical to systematically design stable graphene-based positive electrode materials with high potential for lithium-ion battery applications. In this work, we study the thermodynamic and redox properties of graphene functionalized with carbonyl and hydroxyl groups, and the evolution of these properties with the number, types and distribution of functional groups by employing the density functional theory method. It is found that the redox potential of the functionalized graphene is sensitive to the types, number, and distribution of oxygen functional groups. First, the carbonyl group induces higher redox potential than the hydroxyl group. Second, more carbonyl groups would result in higher redox potential. Lastly, the locally concentrated distribution of the carbonyl group is more beneficial to have higher redox potential compared to the uniformly dispersed distribution. In contrast, the distribution of the hydroxyl group does not affect the redox potential significantly. Thermodynamic investigation demonstrates that the incorporation of carbonyl groups at the edge of graphene is a promising strategy for designing thermodynamically stable positive electrode materials with high redox potentials. PMID- 27412374 TI - Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy. AB - AIM: Mitral regurgitation (MR) is a common finding in patients with heart failure with debatable effects on prognosis. Reduction in MR is one of the mechanisms by which cardiac resynchronization therapy (CRT) exerts its beneficial effects. We investigated the prognostic impact of baseline MR and MR persistence after CRT on outcomes of treated patients. METHODS AND RESULTS: We prospectively followed 1122 CRT patients (66.4 +/- 10.3 years, 78% male) who were stratified according to baseline MR severity as having MR- (degree 0-1; n = 508, 45%) or MR+ (degrees 2-3 4; n = 614, 55%). In 916 patients (82%) with MR severity data available at 1-year follow-up, the annual mortality rate was 3.4 and 6.0 per patient-year in the MR- and MR+ group, respectively, with a 1-year incidence rate ratio (IRR) of 1.76 (P < 0.001). Similar results were observed for cardiovascular mortality (1-year IRR 1.72, P = 0.002). When considering survival according to MR severity after CRT, all-cause and cardiovascular mortality were lower in the improved than in the worsened group (1-year IRR 1.87 and 2.33, respectively; both P < 0.001). Regression analysis showed that absence of MR improvement at follow-up was a significant independent predictor of both all-cause and cardiovascular mortality. CONCLUSIONS: Baseline significant MR and absence of MR improvement after CRT are strongly predictive of less favourable long-term survival. PMID- 27412375 TI - Clinical and laboratory predictors of coronary slow flow in coronary angiography. AB - BACKGROUND: The coronary slow-flow phenomenon (CSFP) is a multifactorial angiographic finding with no established pathogenesis. OBJECTIVE: To investigate the role of clinical profile and laboratory findings in patients with CSFP. METHODS: We prospectively recruited 69 patients with angiographically diagnosed CSFP and compared them with 88 patients with normal coronary flow. Demographic information, comorbidities and laboratory analysis, including complete blood count with differential, lipid profile and serum biochemical analysis, were documented and compared in univariate and multivariate analyses. RESULTS: Patients with CSFP were more likely to be male and active smokers. Total cholesterol, triglyceride, hemoglobin and hematocrit, platelet count, mean platelet volume, platelet distribution width and red cell distribution width (RDW) were all higher in patients with CSFP. In multivariate regression analysis, including smoking, total cholesterol, hematocrit, fasting blood glucose and red cell distribution width, except fasting blood glucose, all variables were independently associated with CSFP. Receiver operating characteristic curve analysis revealed a cut-off point of 13.05% for RDW with a sensitivity of 74.6% and a specificity of 77.3% (p<0.001, AUC = 0.802) A cut-off value of 11.35% for PDW had a 89.9% sensitivity and 98.9% specificity for the prediction of CSFP (p<0.001, AUC = 0.970) Conclusion: The changes of circulating blood cell components in patients with CSFP may be indicative of underlying inflammation and endothelial dysfunction that should be investigated in experimental studies. PMID- 27412376 TI - Meta-analyses of the association of HLA-DRB1 alleles with rheumatoid arthritis among Arabs. AB - AIM: Various studies incorporating Arab populations have reported on specific associations between HLA-DRB1 variants and rheumatoid arthritis (RA). We sought to provide an overview on the association of HLA-DRB1 with RA in Arabs using meta analysis tools. METHODS: Data on allele counts and frequencies were compiled from the relevant literature (published before 16 February 2016) and the associations of 13 -DRB1 variants with RA were assessed; relationships were defined in terms of odds ratios (ORs) with a 95% confidence interval. RESULTS: Based on a collection of six studies, risk conferring or protective allele associations were derived from allele counts in 475 RA patients and 1213 controls. Two HLA-DRB1 alleles (-DRB1*04, *10) significantly conferred an increased risk for RA (OR > 2; P < 0.0001). Conversely, four alleles (-DRB1*03, *07, *11 and *13) significantly conferred a protective effect against RA (OR < 1; P < 0.05). No significant associations with RA were found for seven -DRB1 variants (-DRB1*01, *08, *09, *12, *14, *15 and *16). CONCLUSION: With increased statistical power and effect size over individual studies, we present a more robust profile on the association of HLA-DRB1 variants with RA in the Arab ethnicity, and contribute to the global geo-ethnic picture in this context. PMID- 27412377 TI - Investigation of the use of serology and ultrasonography to detect hepatic cystic echinococcosis in Heilongjiang, China, using a Bayesian framework. AB - BACKGROUND: Cystic echinococcosis (CE) is a public health problem in China. However, the prevalence and incidence of CE in Heilongjiang province is still poorly understood. Because there is no perfect gold standard, evaluation of ultrasound (US) and serological methods have been limited. This study evaluated the use of these two diagnostic methods for the diagnosis of CE in suspected cases. METHODS: A total of 522 suspected hepatic CE patients, as well as their demographic and clinical features were collected and detected by immunoglobulin (IgG)-ELISA and US. The marginal posterior densities of sensitivity and specificity for both tests, and the prevalence of hepatic CE amongst participants, were estimated from the product of the likelihood function of observed and latent data by a Bayesian framework. RESULTS: Most of the patients were from rural areas. The most common symptom was upper abdominal pain. The antibody-positive proportion determined by IgG-ELISA was 24.33% (127/522), significantly higher than with US examination (17.24%, 90/522). Bayesian analysis indicated that the estimated prevalence of CE amongst suspected cases was 17.70% (95% credible interval: 14.23-21.54%). The sensitivity and specificity of the ELISA test were 92.63% and 90.37%, and that of US were 93.05% and 98.44%, respectively. Among US-confirmed hepatic CE cases, the male to female ratio was 0.46 and the peak age group was 40-49 years. CONCLUSIONS: The results of the current study demonstrate that CE is present in Heilongjiang province. They also suggest that, whilst ultrasonography appears to be the detection modality of choice, serology may have a use for detection of infection in individuals suspected to be infected. This may have applications for surveillance within the province. PMID- 27412378 TI - Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults. AB - After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1 year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding. PMID- 27412379 TI - Sleep quality and its association with fatigue, symptom burden, and mood in patients with advanced cancer in a clinic for early-phase oncology clinical trials. AB - BACKGROUND: Limited data exist about sleep quality for patients with advanced cancer in phase 1 clinical trials. Poor sleep quality is often not captured as an adverse event, and its association with fatigue, one of the most frequently reported adverse events, is not documented routinely. This article describes sleep quality and its relation with fatigue, symptom burden, and mood in patients recruited from an early-phase clinic for targeted therapy. METHODS: Sleep, fatigue, symptom burden, and mood were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Brief Fatigue Inventory, the MD Anderson Symptom Inventory (MDASI), and the Brief Profile of Mood States, respectively; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was determined from medical records. RESULTS: The sample (n = 256) was 51.2% female, 90% had an ECOG PS of 0 or 1, and the mean age was 58 +/- 0.8 years. Poor sleepers (global PSQI score > 5) constituted 64% of the sample. In separate multiple regression models, poor sleepers had higher levels of fatigue (P < .001), symptom burden (P < .001), and overall mood disturbance (P < .001) than good sleepers. Also, compared with good sleepers, poor sleepers had greater fatigue-related and symptom-related interference with daily activities (all P values < .001). The MDASI disturbed sleep item correlated well with the global PSQI score (Pearson's r = 0.679, P < .001), and this suggests its usefulness as a patient-reported outcome screener of sleep quality in early-phase clinical trials clinics. CONCLUSIONS: Poor sleep quality was a significant problem in the current study and was associated with greater fatigue, symptom burden, and mood disturbance. Sleep quality should be routinely assessed in patients with advanced cancer who are participating in early-phase clinical trials. Cancer 2016;122:3401-3409. (c) 2016 American Cancer Society. PMID- 27412380 TI - Molecular Characterisation and Co-cultivation of Bacterial Biofilm Communities Associated with the Mat-Forming Diatom Didymosphenia geminata. AB - Didymosphenia geminata (Lyngbye) M. Schmidt is a stalked freshwater diatom that is expanding its range globally. In some rivers, D. geminata forms thick and expansive polysaccharide-dominated mats. Like other stalked diatoms, D. geminata cells attach to the substratum with a pad of adhesive extracellular polymeric substance. Research on D. geminata and other diatoms suggests that bacterial biofilm composition may contribute to successful attachment. The aim of this study was to investigate the composition and role of bacterial biofilm communities in D. geminata attachment and survival. Bacterial biofilms were collected at four sites in the main stem of a river (containing D. geminata) and in four tributaries (free of D. geminata). Samples were characterised using automated rRNA intergenic spacer analysis and high-throughput sequencing (HTS). Mat-associated bacteria were isolated and their effect on the early establishment of D. geminata cells assessed using co-culturing experiments. ARISA and HTS data showed differences in bacterial communities between samples with and without D. geminata at two of the four sites. Samples with D. geminata had a higher relative abundance of Sphingobacteria (p < 0.01) and variability in community composition was reduced. Analysis of the 76 bacteria isolated from the mat revealed 12 different strains representing 8 genera. Co-culturing of a Carnobacterium sp. with D. geminata reduced survival (p < 0.001) and attachment (p < 0.001) of D. geminata. Attachment was enhanced by Micrococcus sp. and Pseudomonas sp. (p < 0.001 and p < 0.01, respectively). These data provide evidence that bacteria play a role in the initial attachment and on-going survival of D. geminata, and may partly explain observed distribution patterns. PMID- 27412381 TI - Remote supervision during General Practice training. PMID- 27412382 TI - Nestin overexpression in hepatocellular carcinoma associates with epithelial mesenchymal transition and chemoresistance. AB - BACKGROUND: Nestin expression has been reported to be associated with the prognosis of many solid tumors including human hepatocellular carcinoma (HCC). The present study aimed to identify the role, if any, of Nestin in the chemotherapeutic treatment of HCC. METHODS: We determined Nestin expression in nine HCC cell lines and 220 tissue samples of advanced HCC patients (retrospectively registered) treated with FOLFOX regimens. We examined the correlations between Nestin expression and clinicopatholgical variables and HCC prognosis. Also, we used in vitro and in vivo methods to determine the effects of Nestin expression on HCC cell invasion, migration and chemosensitivity. RESULTS: Nestin expression was significantly increased in HCC tissues and drug-resistant cell lines, and the presence of high levels of Nestin was associated with poor survival. We also showed that drug-resistance occurred in HCC cells with epithelial-mesenchymal transition (EMT), which in turn enhanced invasion ability. Nestin depletion reversed drug-resistance in the Bel-7402/5-FU and Bel-7402/ADM cell lines. Nestin knockdown enhanced chemotherapeutic efficacy in nude mice. Moreover, Nestin up-regulation in Bel-7402 was associated with the activation of Wnt/beta-catenin signaling. CONCLUSION: Our findings suggest that Nestin inhibitors may be useful for the chemotherapy of HCC. PMID- 27412383 TI - Dental caries risk indicators in early childhood and their association with caries polarization in adolescence: a cross-sectional study. AB - BACKGROUND: Based on the hypothesis that biological and social risks accumulate during life, it is important to identify possible dental caries risk indicators from the life course of early childhood and assess their association with caries polarization in adolescence. METHODS: A cross-sectional design was applied to the study, and a multistage cluster sampling method used to draw a representative sample of 1063 18-year-old Lithuanian adolescents. The dental examinations were performed according to the methodology for oral status evaluation recommended by the World Health Organization. Parents of the participating adolescents completed a self-administered questionnaire about their children's life course during early childhood. The interdependence of characteristics was evaluated by chi-square (chi (2)) and Student's (t) criteria. A multivariate logistic regression model with the Significant Caries (SiC) index as an outcome was performed. RESULTS: The mean scores for the number of decayed, missing, and filled teeth (DMFT) and decayed teeth (DT) in the SiC positive group were higher than the corresponding values in the SiC negative group (6.14 [SD, 2.30] and 1.67 [SD, 2.02] vs 1.28 [SD, 1.11] and 0.34 [SD, 0.69], p < 0.001, respectively). Three dental caries risk indicators were identified that were independently associated with a SiC positive outcome: gender(OR = 1.32 [95 % CI: 1.01-1.73]), earlier eruption of the first primary tooth(OR = 1.43 [95 % CI: 1.03-1.97]), and past caries experience in the primary dentition (OR = 1.62 [95 % CI:1.22-2.14]). CONCLUSIONS: These study findings provide reliable evidence that gender, earlier eruption of the first primary tooth, and past caries experience in the primary dentition should be considered to be dental caries risk indicators and may have an adverse effect on caries polarization in adolescence. PMID- 27412385 TI - Differential effect of treadmill exercise on histone deacetylase activity in rat striatum at different stages of development. AB - The study described herein aimed to evaluate the impact of exercise on histone acetylation markers in striatum from Wistar rats at different stages of development. Male Wistar rats were submitted to two different exercise protocols: a single session of treadmill (running 20 min) or a moderate daily exercise protocol (running 20 min for 2 weeks). Striata of rats aged 39 days postnatal (adolescents), 3 months (young adults), and 20 months (aged) were used. The single exercise session induced persistent effects on global HDAC activity only in the adolescent group, given that exercised rats showed decreased HDAC activity 1 and 18 h after training, without effect on histone H4 acetylation levels. However, the moderate daily exercise did not alter any histone acetylation marker in adolescent and mature groups in any time point evaluated after training. In sum, our data suggest that exercise impacts striatal HDAC activity in an age- and protocol-dependent manner. Specifically, this response seems to be more evident during the adolescent period and might suffer a molecular adaptation in response to chronic training. PMID- 27412384 TI - Energetics of muscle contraction: further trials. AB - Knowledge accumulated in the field of energetics of muscle contraction has been reviewed in this article. Active muscle converts chemical energy into heat and work. Therefore, measurements of heat production and mechanical work provide the framework for understanding the process of energy conversion in contraction. In the 1970s, precise comparison between energy output and the associated chemical reactions was performed. It has been found that the two do not match in several situations, resulting in an energy balance discrepancy. More recently, efforts in resolving these discrepancies in the energy balance have been made involving chemical analysis, phosphorus nuclear magnetic resonance spectroscopy, and microcalorimetry. Through reviewing the evidence from these studies, the energy balance discrepancy developed early during isometric contraction has become well understood on a quantitative basis. In this situation energy balance is established when we take into account the binding of Ca to sarcoplasmic proteins such as troponin and parvalbumin, and also the shift of cross-bridge states. On the other hand, the energy balance discrepancy observed during rapid shortening still remains to be clarified. The problem may be related to the essential mechanism of cross-bridge action. PMID- 27412387 TI - Brain networks modulated by subthalamic nucleus deep brain stimulation. AB - Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. PMID- 27412386 TI - Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer. AB - BACKGROUND: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. METHODS: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. RESULTS: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. CONCLUSIONS: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00137852 , registered August 29, 2005. PMID- 27412388 TI - Reply: The underestimated effect of normobaric hyperoxia on cerebral blood flow and its relationship to neuroprotection. PMID- 27412390 TI - The underestimated effect of normobaric hyperoxia on cerebral blood flow and its relationship to neuroprotection. PMID- 27412389 TI - Visual dysfunction in Parkinson's disease. AB - Patients with Parkinson's disease have a number of specific visual disturbances. These include changes in colour vision and contrast sensitivity and difficulties with complex visual tasks such as mental rotation and emotion recognition. We review changes in visual function at each stage of visual processing from retinal deficits, including contrast sensitivity and colour vision deficits to higher cortical processing impairments such as object and motion processing and neglect. We consider changes in visual function in patients with common Parkinson's disease-associated genetic mutations including GBA and LRRK2 . We discuss the association between visual deficits and clinical features of Parkinson's disease such as rapid eye movement sleep behavioural disorder and the postural instability and gait disorder phenotype. We review the link between abnormal visual function and visual hallucinations, considering current models for mechanisms of visual hallucinations. Finally, we discuss the role of visuo perceptual testing as a biomarker of disease and predictor of dementia in Parkinson's disease. PMID- 27412391 TI - The Prevalence and Prognostic Value of Low Muscle Mass in Cancer Patients: A Review of the Literature. AB - : : In several diseases, low muscle mass has been revealed as an unfavorable prognostic factor for outcome. Whether this holds true in patients with solid malignancies as well has increasingly been explored recently. However, this research field is severely hampered by a lack of consensus on how to determine muscle mass in cancer patients and on the definition of low muscle mass. Consequently, the prevalence of low muscle mass varies widely across several studies. Nevertheless, most studies show that, in patients with solid malignancies, low muscle mass is associated with a poor outcome. In the future, more research is needed to get better insight into the best method to determine muscle mass, the exact prognostic value of low muscle mass in diverse tumor types and stages, pathophysiology of low muscle mass in patients with cancer, and ways to intervene and improve muscle mass in patients. This review addresses the current literature on the importance of muscle mass in cancer patients and the methods of muscle measurement. IMPLICATIONS FOR PRACTICE: An increasing number of studies underline the clinical value of low muscle mass as a prognostic factor for adverse outcomes in cancer patients. However, studies show large heterogeneity because of the lack of a standardized approach to measure muscle mass and the lack of reference populations. As a result, the interpretation of data and further progress are severely hampered, hindering the implementation of muscle measurement in oncological care. This review summarizes the methods of diagnosing low muscle mass in cancer patients, the difference between underlying syndromes such as sarcopenia and cachexia, and the association with clinical outcomes described so far. PMID- 27412394 TI - Impact of Oncologists' Attitudes Toward End-of-Life Care on Patients' Access to Palliative Care. AB - BACKGROUND: It is unclear how oncologists' attitudes toward end-of-life (EOL) care affect the delivery of care. The present study examined the association between oncologists' EOL care attitudes and (a) timely specialist palliative care referral, (b) provision of supportive care, and (c) EOL cancer treatment decisions. METHODS: We randomly surveyed 240 oncology specialists at our tertiary care cancer center to assess their attitudes toward EOL care using a score derived from the Jackson et al. qualitative conceptual framework (0 = uncomfortable and 8 = highly comfortable with EOL care). We determined the association between this score and clinicians' report of specialist palliative care referral, provision of supportive care, and EOL cancer treatment decisions. RESULTS: Of the 182 respondents (response rate of 76%), the median composite EOL care score was 6 (interquartile range, 5-7). A higher EOL score was significantly associated with solid tumor oncology (median 7 vs. 6 for hematologic oncology; p = .003), a greater willingness to refer patients with newly diagnosed cancer to specialist palliative care (median, 7 vs. 6; p = .01), greater comfort with symptom management (median, 6 vs. 5; p = .01), and provision of counseling (median, 7 vs. 4; p < .001) but not with cancer treatment decisions. We observed a gradient effect, with higher scores associated with a greater proportion of patients referred to palliative care (score 0-4, 27%; 5, 31%; 6, 32%; 7, 35%; and 8, 45%; p = .007). CONCLUSION: Greater comfort with EOL care was associated with higher rates of specialist palliative care referral and self-reported primary palliative care delivery. More support and education are needed for oncologists who are less comfortable with EOL care. IMPLICATIONS FOR PRACTICE: In the present survey of oncology specialists, most reported that they were comfortable with end of-life (EOL) care, which was in turn, associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care. The results of the present study highlight the need for more support and education for oncologists less comfortable with EOL care because their patients might receive lower levels of both primary and secondary palliative care. PMID- 27412393 TI - Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings. AB - : : Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have compared adjuvant pelvic radiotherapy alone to a combination of radiotherapy and chemotherapy with mixed results. One of the largest of these trials, Postoperative Radiation Therapy in Endometrial Carcinoma 3 (PORTEC-3), has completed accrual and is awaiting data maturation. Metastatic disease is not curable. For tumors of low-grade endometrioid histology with a prolonged time to recurrence, endocrine therapy with a progestin-based regimen is appropriate. Chemotherapy will be used in most other cases, and the standard first-line regimen is carboplatin and paclitaxel. Few chemotherapy agents have been shown to produce meaningful response rates in the second-line setting. Molecularly targeted therapies such as mTOR inhibitors and antiangiogenic agents including bevacizumab have been studied but their role in the armamentarium remains uncertain. IMPLICATIONS FOR PRACTICE: Following surgical resection and staging for endometrial cancer, adjuvant chemotherapy with carboplatin and paclitaxel can be administered to patients with a high risk for recurrence. This includes patients with stage IIIC disease with positive lymph nodes, and high risk subsets of stage I disease such as serous carcinomas. In the metastatic setting, endocrine therapy can be considered, particularly for patients with lower-grade disease and a prolonged time to recurrence. Combined therapy with carboplatin and paclitaxel is the standard of care used for front-line chemotherapy. Antiangiogenic agents are clearly active, but how they should be integrated into treatment is not yet determined. Immunotherapy is a promising direction for patients with mismatch repair-deficient or polymerase epsilon mutated tumors. PMID- 27412392 TI - Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade. AB - : : More than 1.6 million new cases of cancer will be diagnosed in the U.S. in 2016, resulting in more than 500,000 deaths. Although chemotherapy has been the mainstay of treatment in advanced cancers, immunotherapy development, particularly with PD-1 inhibitors, has changed the face of treatment for a number of tumor types. One example is the subset of tumors characterized by mismatch repair deficiency and microsatellite instability that are highly sensitive to PD 1 blockade. Hereditary forms of cancer have been noted for more than a century, but the molecular changes underlying mismatch repair-deficient tumors and subsequent microsatellite unstable tumors was not known until the early 1990s. In this review article, we discuss the history and pathophysiology of mismatch repair, the process of testing for mismatch repair deficiency and microsatellite instability, and the role of immunotherapy in this subset of cancers. IMPLICATIONS FOR PRACTICE: Mismatch repair deficiency has contributed to our understanding of carcinogenesis for the past 2 decades and now identifies a subgroup of traditionally chemotherapy-insensitive solid tumors as sensitive to PD-1 blockade. This article seeks to educate oncologists regarding the nature of mismatch repair deficiency, its impact in multiple tumor types, and its implications for predicting the responsiveness of solid tumors to immune checkpoint blockade. PMID- 27412396 TI - Inactivated antithrombins as fondaparinux antidotes: a promising alternative to haemostatic agents as assessed in vitro in a thrombin-generation assay. AB - In the absence of specific antidote to fondaparinux, two modified forms of antithrombin (AT), one recombinant inactive (ri-AT) and the other chemically inactivated (chi-AT), were designed to antagonise AT-mediated anticoagulants, e. g. heparins or fondaparinux. These inactive ATs were previously proven to effectively neutralise anticoagulant activity associated with heparin derivatives in vitro and in vivo, as assessed by direct measurement of anti-FXa activity. This study was undertaken to evaluate in vitro the effectivity of inactive ATs to reverse anticoagulation by heparin derivatives and to compare them with non specific fondaparinux reversal agents, like recombinant-activated factor VII (rFVIIa) or activated prothrombin-complex concentrate (aPCC), in a thrombin generation assay (TGA). Addition of fondaparinux (3 ug/ml) to normal plasma inhibited thrombin generation by prolonging lag time (LT) as much as 244 % and lowering endogenous thrombin potential (ETP) to 17 % of their control (normal plasma) values. Fondaparinux-anticoagulant activity was reversed by ri-AT and chi AT, as reflected by the corrections of LT up to 117 % and 114 % of its control value, and ETP recovery to 78 % and 63 %, respectively. Unlike ri-AT that had no effect on thrombin generation in normal plasma, chi-AT retained anticoagulant activity that minimises its reversal capacity. However, both ATs were more effective than rFVIIa or aPCC at neutralising fondaparinux and, unlike non specific antidotes, inactive ATs specifically reversed AT-mediated anticoagulant activities, as suggested by their absence of procoagulant activity in anticoagulant-free plasma. PMID- 27412395 TI - Chemoradiotherapy with Brachytherapy or Electron Therapy Boost for Locally Advanced Squamous Cell Carcinoma of the Anus-Reducing the Colostomy Rate. AB - PURPOSE: The aim of this study is to determine overall survival, disease-specific survival and stoma-free survival after treatment of squamous cell carcinoma of the anus with chemoradiotherapy followed by brachytherapy or electron boost in a recent cohort of patients. METHODS: Fifty-two patients (median age 62 years) were treated with radical chemoradiotherapy (mitomycin C, infusional 5-fluorouracil concurrently with conformal radical radiotherapy 45 Gy in 25 fractions over 5 weeks) followed by a radiotherapy boost between 1 December 2000 and 30 April 2011. Follow-up was to 30 November 2014. Thirty-six patients received a boost (15 20 Gy) over 2 days with 192Ir needle brachytherapy for anal canal tumours, and 16 patients received electron beam therapy (20 Gy in 10 fractions in 2 weeks) for anal margin tumours. A defunctioning stoma was only created prior to chemoradiotherapy for fistula or severe anal pain. RESULTS: The overall survival for the 36 patients treated with chemoradiotherapy followed by brachytherapy was 75 % (95 % CI, 61-89) at 5 years, the disease-specific survival was 91 % (95 % CI, 81-101 %), and the stoma-free survival was 97 % (95 % CI, 91-103 %) all at 5 years. For the 16 patients treated with an electron boost for anal margin tumours, the 5-year overall survival, disease-specific survival and stoma-free survival were 68 % (95 % CI, 44-92 %), 78 % (95 % CI, 56-100 %) and 80 % (95 % CI, 60-100 %), respectively. CONCLUSIONS: A very low stoma formation rate can be obtained with radical chemoradiotherapy followed by a brachytherapy boost for squamous cell carcinoma of the anal canal but not with an electron boost for anal margin tumours. PMID- 27412397 TI - Erratum to: Enhanced p62 is Responsible for Mitochondrial Pathway-Dependent Apoptosis and Interleukin-1beta Production at the Early Phase by Monosodium Urate Crystals in Murine Macrophage. PMID- 27412398 TI - Prognostic value of ankle brachial index for future incident heart failure in patients without previous heart failure: data from the impressive predictive value of ankle brachial index for clinical long term outcome in patients with cardiovascular disease examined by ABI study. AB - The ankle brachial index (ABI) is regarded as a predictor of future cardiovascular events. However, the relationship between ABI and incident heart failure (HF) in patients without previous HF is poorly understood. This study aimed to assess the prognostic value of ABI for incident HF in patients without previous HF. The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and measured ABI in 3131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 307 patients were excluded because of previous HF and high (>1.4) ABI. The remaining 2824 patients were stratified into three groups: low ABI (<=0.9), borderline ABI (0.91-0.99), and normal ABI (1.0-1.4). The primary endpoint was hospitalization for HF. Over a mean 4.8-year follow-up, 105 cases of HF occurred. The cumulative incidence of HF was significantly higher in patients with low and borderline ABIs than in those with normal ABI (19.3 vs. 21.0 vs. 10.4 %, log rank P <0.001). In multivariate Cox proportional hazard analysis, low ABI and borderline ABI were independent predictors of incident HF [hazard ratio (HR) 3.00; 95 % confidence interval (CI) 1.70-5.28; P < 0.001 and HR 2.68; 95 % CI 1.35-5.34; P = 0.005, respectively]. In conclusion, low and borderline ABI were strong predictors for future incident HF in patients without previous HF. PMID- 27412399 TI - Accessibility of ophthalmic healthcare for residents of an offshore island-an example of integrated delivery system. AB - BACKGROUND: To assess the utilization of and satisfaction with ophthalmic healthcare provided by integrated delivery system (IDS) since 2000 and vision related quality of life (VRQoL) for residents of an offshore island of Taiwan. METHODS: Facilitators interviewed residents (age >= 50 years) with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) for VRQoL and a questionnaire on clinical information, ophthalmic care utilization and satisfaction. RESULTS: A total of 841 participants (response rate 93.4 %, 841/900) completed the questionnaire survey. Mean age was 63.7 (+/-10. 7) years. The common eye diseases were cataract (44.7 %), dry eye (15.5 %), and glaucoma (8.7 %). Among the participants, 61.0 % sought ophthalmic care under the IDS in the past year and 17.6 % experienced unmet ophthalmic needs in the past 6 months. Satisfaction with ophthalmic care under the IDS was 88.1 %. Determinants of dissatisfaction under the IDS were distance to healthcare facility and VRQoL. Predictors of VRQoL included age, residential area, marital status, occupation, comorbid condition, commercial insurance, household income, cataracts and glaucoma. CONCLUSIONS: The implementation of IDS improves accessibility of ophthalmic care for residents of an offshore island. Geographic proximity to avail healthcare facility and VRQoL affect satisfaction with the IDS. PMID- 27412400 TI - Significance of Lipid-Free and Lipid-Associated ApoA-I in Cellular Cho-lesterol Efflux. AB - The structure and stability of apolipoprotein (apo)A-I, the major apolipoprotein of human plasma high-density lipoproteins (HDL), determine the efficiency of the protein in the process of HDL generation and affect HDL properties in binding and exchanging its constituents, thus playing an essential role in reverse cholesterol transport. The equilibrium stability of an apoA-I molecule at the lipid interface (12.7 kcal/mol) predicted by a thermodynamic cycle for apolipoprotein folding-unfolding in water and at interface, largely exceeds apoA I helix stability in HDL against chemical denaturation (3-5 kcal/mol). An ensemble of structures of lipid-bound apoA-I with different stabilities is assumed to exist. The conformational transitions between apoA-I conformers in water and lipid phases correspond to Lumry-Eyring model OL <=> CL => MW, where OL and CL are open and closed structures of HDLbound apoA-I, and MW is the molten globule in water. The model includes the reversible foldingunfolding transitions of N- and C-domains at HDL interface and apolipoprotein irreversible dissociation. We gathered published data on cholesterol efflux for apoA-I proteins with missense mutations in C-domain and calculated the stability of these mutants as a change of free energy relative to a wild type protein. Significant negative correlation was found between this stability and the efficiency of cAMP-stimulated cholesterol efflux. Thus, besides the known role of C-domain hydrophobicity, structure-destabilizing changes may significantly contribute to ABCA1-mediated cholesterol efflux by free apolipoprotein. PMID- 27412402 TI - Genetic optimization of a bacteriophage-delivered alkaline phosphatase reporter to detect Escherichia coli. AB - A large fraction of foodborne illnesses are linked to (~46%) leafy green vegetables contaminated by pathogens harbored in agricultural water. To prevent this, accurate point-of-production detection tools are required to identify and quantify bacterial contaminants in produce before consumers are impacted. In this study, a proof-of-concept model was engineered for a phage-based Escherichia coli detection system. We engineered the coliphage T7 to express alkaline phosphatase (ALP) to serve as the signal for E. coli detection. Wild type phoA (T7ALP) and a dominant-active allele, phoA D153G D330N (T7ALP*) was inserted into the T7 genome, with engineered constructs selected by CRISPR-mediated cleavage of unaltered chromosomes and confirmed by PCR. Engineered phages and E. coli target cells were co-incubated for 16 hours to produce lysates with liberated ALP correlated with input cell concentrations. A colorimetric assay used p nitrophenyl phosphate (pNPP) to demonstrate significant ALP production by T7ALP and T7ALP* compared to the vector control (T7EV) (p<= 0.05). Furthermore, T7ALP* produced 2.5-fold more signal than T7ALP (p<= 0.05) at pH 10. Due to the increase in signal for the modified ALP* allele, we assessed T7ALP* sensitivity in a dose responsive manner. We observed 3-fold higher signal for target cell populations as low as ~2 * 10(5) CFU mL(-1) (p<= 0.05 vs. no-phage control). PMID- 27412401 TI - Roles of OA1 octopamine receptor and Dop1 dopamine receptor in mediating appetitive and aversive reinforcement revealed by RNAi studies. AB - Revealing reinforcing mechanisms in associative learning is important for elucidation of brain mechanisms of behavior. In mammals, dopamine neurons are thought to mediate both appetitive and aversive reinforcement signals. Studies using transgenic fruit-flies suggested that dopamine neurons mediate both appetitive and aversive reinforcements, through the Dop1 dopamine receptor, but our studies using octopamine and dopamine receptor antagonists and using Dop1 knockout crickets suggested that octopamine neurons mediate appetitive reinforcement and dopamine neurons mediate aversive reinforcement in associative learning in crickets. To fully resolve this issue, we examined the effects of silencing of expression of genes that code the OA1 octopamine receptor and Dop1 and Dop2 dopamine receptors by RNAi in crickets. OA1-silenced crickets exhibited impairment in appetitive learning with water but not in aversive learning with sodium chloride solution, while Dop1-silenced crickets exhibited impairment in aversive learning but not in appetitive learning. Dop2-silenced crickets showed normal scores in both appetitive learning and aversive learning. The results indicate that octopamine neurons mediate appetitive reinforcement via OA1 and that dopamine neurons mediate aversive reinforcement via Dop1 in crickets, providing decisive evidence that neurotransmitters and receptors that mediate appetitive reinforcement indeed differ among different species of insects. PMID- 27412406 TI - Review of the Diagnostic Challenges of Lambert-Eaton Syndrome Revealed Through Three Case Reports. AB - Lambert-Eaton syndrome (LES) is a rare immune-mediated disorder characterized by proximal leg weakness, autonomic symptoms and hypoactive tendon reflexes. The paraneoplastic form is associated with small-cell lung cancer in 50-60% of cases, whereas the remaining cases are found in younger adults with a higher likelihood of coexisting autoimmune disease. The early recognition of LES is crucial for improving clinical outcomes but remains a major challenge. In this review, we analyze the clinical characteristics and diagnostic considerations in treating LES through a series of three case studies, one of which showed definitive response to pyridostigmine and corticosteroid combination therapy, followed by spontaneous remission. Patients were assessed by image-based screening, serological testing and electrophysiological evaluations, which included respiratory and autonomic testing. A better understanding of the common pitfalls in the clinical, serological and neurophysiologic diagnosis of LES through assessment of typical LES dysfunction throughout the nervous system should enable improved recognition and treatment of this syndrome. PMID- 27412405 TI - 3D Platinum-Lead Nanowire Networks as Highly Efficient Ethylene Glycol Oxidation Electrocatalysts. AB - A large-scalable wet-chemical approach to create networked Pt-Pb nanowires (NWs) with tunable compositions is reported. Due to their 3D networked structure, alloy effect, rich defects/steps, and antipoisoning property of Pb, the networked Pt-Pb NWs exhibit the best activity and durability towards ethylene glycol oxidation reaction (EGOR), compared with the networked Pt NWs and Pt/C. PMID- 27412407 TI - The Loss of a Psychiatric Nursing Legend: Grayce McVeigh Sills, 1926-2016. PMID- 27412403 TI - Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis. AB - Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity. PMID- 27412408 TI - Psychotic-Like Experiences and Psychological Distress: The Role of Resilience. AB - BACKGROUND: The occurrence of psychotic-like experiences and schizotypal features in the general nonclinical population may imply a connection with psychosis related liability. OBJECTIVE: This study was designed to examine the role of resilience in the relationship of hallucination and delusion-like experiences and schizotypal features to psychological distress in a nonclinical sample. DESIGN: The study sample (n = 432 university students) was selected through a stratified cluster sampling procedure, and measures of hallucination proneness, delusion proneness, schizotypal personality, and psychological distress were administered. RESULTS: While all three indices of psychotic-like experiences correlated with one another, only hallucination proneness and schizotypal personality features correlated with psychological distress and only schizotypal traits correlated with resilience. Schizotypy was found to have an indirect effect on distress through resilience. CONCLUSIONS: Findings imply the possibility of two types of schizotypy, with high or low resilience. It appears that schizotypes with low resilience may be susceptible to adversity and mental disorders, while high resilience may be protective. PMID- 27412409 TI - Editing Perceptions About Psychiatric-Mental Health Nursing. PMID- 27412410 TI - APNA 29th Annual Conference, October 28-31, 2015, Lake Buena Vista, Florida. PMID- 27412411 TI - Downregulation of Heme Oxygenase 1 (HO-1) Activity in Hematopoietic Cells Enhances Their Engraftment After Transplantation. AB - Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme that not only catalyzes the degradation of heme (e.g., released from erythrocytes) but also has an important function in various physiological and pathophysiological states associated with cellular stress, such as ischemic/reperfusion injury. HO-1 has a well-documented anti-inflammatory potential, and HO-1 has been reported to have a negative effect on adhesion and migration of neutrophils in acute inflammation in a model of peritonitis. This finding is supported by our recent observation that hematopoietic stem progenitor cells (HSPCs) from HO-1 KO mice are easy mobilizers, since they respond better to peripheral blood chemotactic gradients than wild-type littermates. Based on these findings, we hypothesized that transient inhibition of HO-1 by nontoxic small-molecule inhibitors would enhance migration of HSPCs in response to bone marrow chemoattractants and thereby facilitate their homing. To directly address this issue, we generated several human hematopoietic cell lines in which HO-1 was upregulated or downregulated. We also exposed murine and human BM-derived cells to small-molecule activators and inhibitors of HO-1. Our results indicate that HO-1 is an inhibitor of hematopoietic cell migration in response to crucial BM homing chemoattractants such as stromal-derived factor 1 (SDF-1) and sphingosine-1-phosphate (S1P). Most importantly, our in vitro and in vivo animal experiments demonstrate for the first time that transiently inhibiting HO-1 activity in HSPCs by small-molecule inhibitors improves HSPC engraftment. We propose that this simple and inexpensive strategy could be employed in the clinical setting to improve engraftment of HSPCs, particularly in those situations in which the number of HSPCs available for transplant is limited (e.g., when transplanting umbilical cord blood). PMID- 27412412 TI - Genetic diversity of Ulva prolifera population in Qingdao coastal water during the green algal blooms revealed by microsatellite. AB - Green tides have occurred in Qingdao coast in China for seven consecutive years from 2007 to 2013. To provide information on the genetic structure of these blooms, 210 free-floating green algae samples isolated from the green tide in Qingdao coast on June 19, 2013 were identified based on the ITS, rbcL and 5S sequence, and genetic diversity was investigated by microsatellite markers. According to ITS, rbcL and 5S sequence, all the 210 samples belonged to Ulva prolifera. Nei's genetic diversity and Shannon index estimated using eight microsatellite markers indicated that the genetic diversity of U. prolifera population within Qingdao's green bloom in 2013 was low. Taking into account previous reports about life history and physiology of U. prolifera, we proposed that the limited origin area of the free-floating biomass and asexual reproduction of U. prolifera might be responsible for the lower diversity of free floating U. prolifera. PMID- 27412413 TI - Features of Human CD3+CD20+ T Cells. AB - Monoclonal Abs against CD20 reduce the number of relapses in multiple sclerosis (MS); commonly this effect is solely attributed to depletion of B cells. Recently, however, a subset of CD3(+)CD20(+) T cells has been described that is also targeted by the anti-CD20 mAb rituximab. Because the existence of cells coexpressing CD3 and CD20 is controversial and features of this subpopulation are poorly understood, we studied this issue in detail. In this study, we confirm that 3-5% of circulating human T cells display CD20 on their surface and transcribe both CD3 and CD20. We report that these CD3(+)CD20(+) T cells pervade thymus, bone marrow, and secondary lymphatic organs. They are found in the cerebrospinal fluid even in the absence of inflammation; in the cerebrospinal fluid of MS patients they occur at a frequency similar to B cells. Phenotypically, these T cells are enriched in CD8(+) and CD45RO(+) memory cells and in CCR7(-) cells. Functionally, they show a higher frequency of IL-4-, IL-17 , IFN-gamma-, and TNF-alpha-producing cells compared with T cells lacking CD20. CD20-expressing T cells respond variably to immunomodulatory treatments given to MS patients: they are reduced by fingolimod, alemtuzumab, and dimethyl fumarate, whereas natalizumab disproportionally increases them in the blood. After depletion by rituximab, they show earlier and higher repopulation than CD20(+) B cells. Taken together, human CD3(+)CD20(+) T cells pervade lymphatic organs and the cerebrospinal fluid, have a strong ability to produce different cytokines, and respond to MS disease modifying drugs. PMID- 27412414 TI - Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. AB - EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II(+) cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs. PMID- 27412415 TI - Bacillus Calmette-Guerin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses. AB - One third of the global population is estimated to be latently infected with Mycobacterium tuberculosis We performed a phase I randomized controlled trial of isoniazid preventive therapy (IPT) before revaccination with bacillus Calmette Guerin (BCG) in healthy, tuberculin skin test-positive (>=15-mm induration), HIV negative South African adults. We hypothesized that preclearance of latent bacilli with IPT modulates BCG immunogenicity following revaccination. Frequencies and coexpression of IFN-gamma, TNF-alpha, IL-2, IL-17, and/or IL-22 in CD4 T cells and IFN-gamma-expressing CD8 T, gammadelta T, CD3(+)CD56(+) NKT like, and NK cells in response to BCG were measured using whole blood intracellular cytokine staining and flow cytometry. We analyzed 72 participants who were revaccinated with BCG after IPT (n = 33) or without prior IPT (n = 39). IPT had little effect on frequencies or cytokine coexpression patterns of M. tuberculosis- or BCG-specific responses. Revaccination transiently boosted BCG specific Th1 cytokine-expressing CD4, CD8, and gammadelta T cells. Despite high frequencies of IFN-gamma-expressing BCG-reactive CD3(+)CD56(+) NKT-like cells and CD3(-)CD56(dim) and CD3(-)CD56(hi) NK cells at baseline, BCG revaccination boosted these responses, which remained elevated up to 1 y after revaccination. Such BCG-reactive memory NK cells were induced by BCG vaccination in infants, whereas in vitro IFN-gamma expression by NK cells upon BCG stimulation was dependent on IL-12 and IL-18. Our data suggest that isoniazid preclearance of M. tuberculosis bacilli has little effect on the magnitude, persistence, or functional attributes of lymphocyte responses boosted by BCG revaccination. Our study highlights the surprising durability of BCG-boosted memory NKT-like and NK cells expressing antimycobacterial effector molecules, which may be novel targets for tuberculosis vaccines. PMID- 27412416 TI - CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata. AB - Alopecia areata (AA) is an autoimmune disease of the hair follicle that results in hair loss of varying severity. Recently, we showed that IFN-gamma-producing NKG2D(+)CD8(+) T cells actively infiltrate the hair follicle and are responsible for its destruction in C3H/HeJ AA mice. Our transcriptional profiling of human and mouse alopecic skin showed that the IFN pathway is the dominant signaling pathway involved in AA. We showed that IFN-inducible chemokines (CXCL9/10/11) are markedly upregulated in the skin of AA lesions, and further, that the IFN inducible chemokine receptor, CXCR3, is upregulated on alopecic effector T cells. To demonstrate whether CXCL9/10/11 chemokines were required for development of AA, we treated mice with blocking Abs to CXCR3, which prevented the development of AA in the graft model, inhibiting the accumulation of NKG2D(+)CD8(+) T cells in the skin and cutaneous lymph nodes. These data demonstrate proof of concept that interfering with the Tc1 response in AA via blockade of IFN-inducible chemokines can prevent the onset of AA. CXCR3 blockade could be approached clinically in human AA with either biologic or small-molecule inhibition, the latter being particularly intriguing as a topical therapeutic. PMID- 27412419 TI - Tiny channels, giant dreams. PMID- 27412418 TI - Biophysical and Biochemical Characterization of Avian Secretory Component Provides Structural Insights into the Evolution of the Polymeric Ig Receptor. AB - The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the mucosa, where proteolytic cleavage releases the ectodomain (secretory component [SC]) as an integral component of secretory Abs, or as an unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization is variable: mammalian SC has five domains (D1-D5), whereas avian, amphibian, and reptilian SC lack the D2 domain, and fish SC lacks domains D2-D4. In this study, we used double electron-electron resonance spectroscopy and surface plasmon resonance binding studies to characterize the structure, dynamics, and ligand binding properties of avian SC, avian SC domain variants, and a human SC (hSC) variant lacking the D2 domain. These experiments demonstrated that, unlike hSC, which adopts a compact or "closed" domain arrangement, unliganded avian SC is flexible and exists in both closed and open states, suggesting that the mammalian SC D2 domain stabilizes the closed conformation observed for hSC D1-D5. Experiments also demonstrated that avian and mammalian pIgR share related, but distinct, mechanisms of ligand binding. Together, our data reveal differences in the molecular recognition mechanisms associated with evolutionary changes in the pIgR protein. PMID- 27412417 TI - Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines. AB - There is great interest in the development of Ab-inducing subunit vaccines targeting infections, including HIV, malaria, and Ebola. We previously reported that adenovirus vectored vaccines are potent in priming Ab responses, but uncertainty remains regarding the optimal approach for induction of humoral immune responses. In this study, using OVA as a model Ag, we assessed the magnitude of the primary and anamnestic Ag-specific IgG responses of mice to four clinically relevant vaccine formulations: replication-deficient adenovirus; modified vaccinia Ankara (a poxvirus); protein with alum; and protein in the squalene oil-in-water adjuvant Addavax. We then used flow cytometric assays capable of measuring total and Ag-specific germinal center (GC) B cell and follicular Th cell responses to compare the induction of these responses by the different formulations. We report that adenovirus vectored vaccines induce Ag insert-specific GC B cell and Ab responses of a magnitude comparable to those induced by a potent protein/squalene oil-in-water formulation whereas-despite a robust overall GC response-the insert-specific GC B cell and Ab responses induced by modified vaccinia Ankara were extremely weak. Ag-specific follicular Th cell responses to adenovirus vectored vaccines exceeded those induced by other platforms at day 7 after immunization. We found little evidence that innate immune activation by adenovirus may act as an adjuvant in such a manner that the humoral response to a recombinant protein may be enhanced by coadministering with an adenovirus lacking a transgene of interest. Overall, these studies provide further support for the use of replication-deficient adenoviruses to induce humoral responses. PMID- 27412421 TI - Parents' perspectives on a collaborative approach to the application of the Handwriting Without Tears((r)) programme with children with Down syndrome. AB - BACKGROUND: The active involvement of parents and children in goal setting and intervention is integral to contemporary occupational therapy process models. However, parental perspectives on collaborative handwriting intervention are limited. This paper presents parental perspectives on a three-way collaboration involving teachers, parents and an occupational therapist in the application of Handwriting Without Tears((r)) (HWT((r)) ) with children with Down syndrome. METHODS: Within a larger mixed methods study, 44 parents completed purpose designed questionnaires and six parents participated in a focus group, post 8 months of programme implementation. Both methods gathered parent's perspectives on the usefulness and limitations of applying HWT((r)) . The focus group explored collaboration in depth. Analysis involved triangulation of data from descriptive analysis of numerical data with content analysis of open-ended questions and focus group data. FINDINGS: Enablers of parent-child engagement in HWT((r)) were identified as; the parent-child-friendly aspects of HWT((r)) , the teacher involvement ensuring continuity which eased demands on parents, the ongoing support/guidance of the occupational therapist and the child's involvement in HWT((r)) group intervention. The occupational therapists' involvement was reported as essential to encouraging teacher/parent involvement. Barriers to child-parent engagement included fluctuations in child health, mood, attention span and time limitations including the child's involvement in other therapy programmes. CONCLUSIONS: Parents perceived the HWT((r)) and the three-way collaborative approach as enabling active parent-child engagement in handwriting intervention. This approach warrants further investigation. Findings have the potential to inform practice guidelines and pre- and post-graduation education related to collaborative handwriting intervention with children with Down syndrome and their families. PMID- 27412420 TI - Napsin A/p40 antibody cocktail for subtyping non-small cell lung carcinoma on cytology and small biopsy specimens. AB - BACKGROUND: Subtyping non-small cell lung carcinomas (NSCLC) into adenocarcinoma (ACA) or squamous cell carcinoma (SQCC) is important for treatment and specimen triage for molecular studies. To preserve tissue for molecular studies in cytology/small biopsy specimens, a 2-antibody cocktail for NSCLC subtyping was developed. METHODS: Markers for lung ACA (thyroid transcription factor 1 and napsin A) and SQCC (cytokeratin 5/6 and p40) were evaluated on tissue microarrays (TMAs) with 143 ACA and 98 SQCC specimens. The napsin A/p40 combination was selected for NSCLC subtyping and validated on the TMA as well as on a cohort of cell block/small biopsy specimens from 80 poorly differentiated NSCLCs. RESULTS: Using TMA analysis, the napsin A-positive (+)/p40+/- immunophenotype identified ACA with 94% sensitivity and 100% specificity, whereas the napsin A (negative) /p40+ immunophenotype identified SQCC with 100% sensitivity and specificity. On the validation cohort of 80 cell block and small biopsy specimens, the napsin A/p40 cocktail accurately subtyped 63 of 70 NSCLC (90%) as ACA or SQCC using the subsequent surgical resection as reference histology. Of the remaining 17 cases, 15 were classified as NSCLC-not otherwise specified based on a napsin A-/p40- immunophenotype; their corresponding resections were diagnosed as ACA (7 cases), large cell carcinoma (7 cases), or pleomorphic carcinoma (1 case). Two additional large cell carcinoma cases showed a napsin A-/p40+ or napsin A+/p40+ profile in the preoperative cell block/small biopsy sample. CONCLUSIONS: A napsin A/p40 cocktail can accurately subtype NSCLC into ACA and SQCC in most cell block/small biopsy specimens of poorly differentiated NSCLC. In the minority of cases in which the napsin A/p40 immunophenotype is indeterminate, additional stains may be necessary for precise classification. Cancer Cytopathol 2016;124:472-84. (c) 2016 American Cancer Society. PMID- 27412422 TI - Prevalence and risk factors for functional bowel disorders in South China: a population based study using the Rome III criteria. AB - BACKGROUND: Functional bowel disorders (FBDs) such as irritable bowel syndrome (IBS) impact on quality of life and health care resources. It is uncertain whether patients with functional digestive symptoms have similar characteristics in different populations. This population-based study assessed the prevalence and identified risk factors for these disorders in South-East China. METHODS: Five communities were selected at random and invitations distributed to a representative sample (block randomization). Questionnaires were completely supervised by investigators. Demographic and medical data with FBD symptoms (Rome III criteria), psychological condition, life event stress, and quality of life were collected. KEY RESULTS: Functional bowel disorder prevalence was 41.6% in 1999/2115 (94.5%) completed questionnaires: 9.9% functional constipation (FC), 6.8% bloating (FB), 6.5% diarrhea (FD), 5.9% IBS (IBS-D 47.1%, IBS-M 23.9%, IBS-C 12.8%, IBS-U 16.2%), and 12.6% unspecified. Similar numbers of men and women had FBDs or IBS (overall; 51.3% male vs 48.7% female, P=.796); however, there was female predominance in FC (62.1%, P<.001) and FB (58.5%, P=.038). FBDs were associated with greater anxiety, depression, life event stress, and a lower quality of life compared with those without symptoms (all, P<.0001). Logistic regression identified medical co-morbidity, anxiety/depression, and life event stress as independent risk factors for these disorders. CONCLUSIONS & INFERENCES: Functional bowel disorders are as common in South China as in western populations. A similar number of men and women report FBDs and IBS. Only FC and FB are more prevalent in females. Independent risk factors associated with FBDs included physical and psychosocial stressors. PMID- 27412423 TI - Illness representations, coping, and illness outcomes in people with cancer: a systematic review and meta-analysis. AB - OBJECTIVE: Cancer is associated with negative health and emotional outcomes in those affected by it, suggesting the need to better understand the psychosocial determinants of illness outcomes and coping. The common sense model is the leading psychological model of self-regulation in the face of illness and assumes that subjective illness representations explain how people attempt to cope with illness. This systematic review and meta-analysis examines the associations of the common sense model's illness representation dimensions with health and coping outcomes in people with cancer. METHODS: A systematic literature search located 54 studies fulfilling the inclusion criteria, with 38 providing sufficient data for meta-analysis. A narrative review of the remaining studies was also conducted. RESULTS: Random-effects models revealed small to moderate effect sizes (Fisher Z) for the relations between illness representations and coping behaviors (in particular between control perceptions, problem-focused coping, and cognitive reappraisal) and moderate to large effect sizes between illness representations and illness outcomes (in particular between identity, consequences, emotional representations, and psychological distress). The narrative review of studies with insufficient data provided similar results. CONCLUSIONS: The results indicate how illness representations relate to illness outcomes in people with cancer. However, more high-quality studies are needed to examine causal effects of illness representations on coping and outcomes. High heterogeneity indicates potential moderators of the relationships between illness representations and health and coping outcomes, including diagnostic, prognostic, and treatment related variables. This review can inform the design of interventions to improve coping strategies and mental health outcomes in people with cancer. PMID- 27412424 TI - Medical Scribes: Salvation for Primary Care or Workaround for Poor EMR Usability? PMID- 27412425 TI - What They Don't Teach You. PMID- 27412427 TI - Lifetime impact of injury on education, employment and income for Australians of labour force participation age. AB - BACKGROUND: Research shows that employment rates are low post injury. AIMS: To quantify the economic impact of a long-term injury and identify whether having a tertiary level of education attainment would offset this impact. METHODS: Cross sectional analysis of the 2012 Survey of Disability, Aging and Carers, which is nationally representative of the Australian population. RESULTS: Males with any long-term injury had incomes 41% less than males with no chronic health condition (95% confidence interval [CI] -49.3%, -31.6%). For males with a long-term injury, there was no significant difference in the likelihood of being not in the labour force between those with and without a tertiary qualification (odds ratio [OR] 0.83, 95% CI 0.45-1.52). There was no significant difference in the incomes of females with any long-term injury compared with those with no chronic health conditions. For females with a long-term injury, there was a significant difference in the likelihood of being not in the labour force between those with and without a tertiary qualification (OR 0.37, 95% CI 0.17-0.80). If men with a long-term injury had the same probability of participating in the workforce as women, the percentage of men not in the labour force would reduce from 37 to 18%. CONCLUSIONS: Having a long-term injury was a significant personal cost in terms of labour force absence and lower income for males regardless of higher education attainment. For females, sustaining a long-term injury did not appear to significantly affect income. PMID- 27412426 TI - Race/Ethnicity and Adoption of a Population Health Management Approach to Colorectal Cancer Screening in a Community-Based Healthcare System. AB - BACKGROUND: Screening outreach programs using population health management principles offer services uniformly to all eligible persons, but racial/ethnic colorectal cancer (CRC) screening patterns in such programs are not well known. OBJECTIVE: To examine the association between race/ethnicity and the receipt of CRC screening and timely follow-up of positive results before and after implementation of a screening program. DESIGN: Retrospective cohort study of screen-eligible individuals at the Kaiser Permanente Northern California community-based integrated healthcare delivery system (2004-2013). SUBJECTS: A total of 868,934 screen-eligible individuals 51-74 years of age at cohort entry, which included 662,872 persons in the period before program implementation (2004 2006), 654,633 during the first 3 years after implementation (2007-2009), and 665,268 in the period from 4 to 7 years (2010-2013) after program implementation. INTERVENTION: A comprehensive system-wide long-term effort to increase CRC that included leadership alignment, goal-setting, and quality assurance through a PHM approach, using mailed fecal immunochemical testing (FIT) along with offering screening at office visits. MAIN MEASURES: Differences over time and by race/ethnicity in up-to-date CRC screening (overall and by test type) and timely follow-up of a positive screen. Race/ethnicity categories included non-Hispanic white, non-Hispanic black, Hispanic/Latino, Asian/Pacific Islander, Native American, and multiple races. KEY RESULTS: From 2004 to 2013, age/sex-adjusted CRC screening rates increased in all groups, including 35.2 to 81.1 % among whites and 35.6 to 78.0 % among blacks. Screening rates among Hispanics (33.1 to 78.3 %) and Native Americans (29.4 to 74.5 %) remained lower than those for whites both before and after program implementation. Blacks, who had slightly higher rates before program implementation (adjusted rate ratio [RR] = 1.04, 99 % CI: 1.02-1.05), had lower rates after program implementation (RR for period from 4 to 7 years = 0.97, 99 % CI: 0.96-0.97). There were also substantial improvements in timely follow-up of positive screening results. CONCLUSIONS: In this screening program using core PHM principles, CRC screening increased markedly in all racial/ethnic groups, but disparities persisted for some groups and developed in others, which correlated with levels of adoption of mailed FIT. PMID- 27412428 TI - Work stress, poor recovery and burnout in teachers. AB - BACKGROUND: Both work stress and poor recovery have been shown to contribute to the development of burnout. However, the role of recovery as a mediating mechanism that links work stress to burnout has not been sufficiently addressed in research. AIMS: To examine recovery as a mediator in the relationship between work stress and burnout among teachers. METHODS: A cross-sectional study of Finnish primary school teachers, in whom burnout was measured with the Maslach Burnout Inventory-General Survey and work stress was conceptualized using the effort-reward imbalance (ERI) model. Recovery was measured with the Recovery Experience Questionnaire and the Jenkins Sleep Problems Scale. Multiple linear regression analyses and bootstrap mediation analyses adjusted for age, gender and total working hours were performed. RESULTS: Among the 76 study subjects, high ERI was associated with burnout and its dimensions of exhaustion, cynicism and reduced professional efficacy. Poor recovery experiences, in terms of low relaxation during leisure time, partially mediated the relationship between ERI and reduced professional efficacy. Sleep problems, in the form of non-restorative sleep, partially mediated the relationship between ERI and both burnout and exhaustion. CONCLUSIONS: Supporting a balance between effort and reward at work may enhance leisure time recovery and improve sleep quality, as well as help to reduce burnout rates. PMID- 27412429 TI - Pregnancy outcome in partners of male professional divers in Norway. AB - BACKGROUND: Diving is associated with both acute and long-term effects in several organ systems. Reduced semen quality after extreme diving and a reduced proportion of males in the offspring of divers have previously been reported. AIMS: To study pregnancy outcomes in partners of professional male divers. METHODS: The cohort of divers registered with the Norwegian Inshore Diving Registry was linked to the Medical Birth Registry of Norway (MBRN). RESULTS: In total, 6186 male divers had 10395 children registered in the MBRN during the study period. Of these, 52% were boys, compared to 51% in the general population. The partners of a subgroup of divers who were most likely to be occupationally exposed at the time of conception reported that early miscarriage was more frequent (27%) than in the general population (21%; relative risk 1.21, 95% confidence interval 1.05-1.39). Otherwise, there was a lower risk of adverse pregnancy outcomes such as preterm birth, stillbirth, low birthweight, small for gestational age and low Apgar score compared to the general population. Birthweight above 4000g was more frequent. CONCLUSIONS: We observed no reduced sex ratio in the offspring of occupational divers. Except for an increase in self reported early miscarriage in the partners of exposed divers, we observed no excess risk of any of the adverse perinatal pregnancy outcomes studied. PMID- 27412430 TI - Right Atrial Approach for Ablation of Ventricular Arrhythmias Arising From the Left Posterior-Superior Process of the Left Ventricle. AB - BACKGROUND: The posterior-superior process of the left ventricle (PSP-LV) is the most inferior and posterior aspect of the basal LV that extends posteriorly to the plane of the tricuspid valve. The PSP-LV is anatomically adjacent to the inferior and medial aspect of the right atrium (RA). We report a series of patients with ventricular arrhythmias (VAs) arising from the PSP-LV and describe a mapping and ablation approach from the RA guided by intracardiac echocardiography. METHODS AND RESULTS: Mapping and ablation of the PSP-LV with an RA approach under intracardiac echocardiography guidance were performed in 5 patients with VAs (aged 44+/-14 years, 2 males) who had failed ablation attempts from multiple endocardial and epicardial (1 patient) sites. Mapping of the PSP-LV from the adjacent inferomedial RA was performed at sites anatomically opposite to the earliest endocardial site of activation under direct intracardiac echocardiography visualization. From the RA side of the PSP-LV, a small atrial signal and a larger ventricular signal were recorded in each case, with an activation time of 32+/-7 ms pre-QRS (versus 16+/-5 ms pre-QRS in the LV endocardium; P=0.068). We were able to capture the LV from these sites. Cryoablation was performed in 2 patients, and radiofrequency was used in the remaining 3 cases. In all patients, ablation from the RA eliminated the arrhythmia. All patients remained free of recurrent VAs after a mean follow-up of 12 (7-16) months. There were no immediate or long-term complications. CONCLUSIONS: The PSP-LV can be a site of origin of VAs, which can be successfully eliminated from the adjacent RA under direct intracardiac echocardiographic visualization. PMID- 27412432 TI - Carbon Storage Patterns of Caragana korshinskii in Areas of Reduced Environmental Moisture on the Loess Plateau, China. AB - Precipitation patterns are influenced by climate change and profoundly alter the carbon sequestration potential of ecosystems. Carbon uptake by shrubbery alone accounts for approximately one-third of the total carbon sink; however, whether such uptake is altered by reduced precipitation is unclear. In this study, five experimental sites characterised by gradual reductions in precipitation from south to north across the Loess Plateau were used to evaluate the Caragana korshinskii's functional and physiological features, particularly its carbon fixation capacity, as well as the relationships among these features. We found the improved net CO2 assimilation rates and inhibited transpiration at the north leaf were caused by lower canopy stomatal conductance, which enhanced the instantaneous water use efficiency and promoted plant biomass as well as carbon accumulation. Regional-scale precipitation reductions over a certain range triggered a distinct increase in the shrub's organic carbon storage with an inevitable decrease in the soil's organic carbon storage. Our results confirm C. korshinskii is the optimal dominant species for the reconstruction of fragile dryland ecosystems. The patterns of organic carbon storage associated with this shrub occurred mostly in the soil at wetter sites, and in the branches and leaves at drier sites across the arid and semi-arid region. PMID- 27412431 TI - Identification of novel candidate drivers connecting different dysfunctional levels for lung adenocarcinoma using protein-protein interactions and a shortest path approach. AB - Tumors are formed by the abnormal proliferation of somatic cells with disordered growth regulation under the influence of tumorigenic factors. Recently, the theory of "cancer drivers" connects tumor initiation with several specific mutations in the so-called cancer driver genes. According to the differentiation of four basic levels between tumor and adjacent normal tissues, the cancer drivers can be divided into the following: (1) Methylation level, (2) microRNA level, (3) mutation level, and (4) mRNA level. In this study, a computational method is proposed to identify novel lung adenocarcinoma drivers based on dysfunctional genes on the methylation, microRNA, mutation and mRNA levels. First, a large network was constructed using protein-protein interactions. Next, we searched all of the shortest paths connecting dysfunctional genes on different levels and extracted new candidate genes lying on these paths. Finally, the obtained candidate genes were filtered by a permutation test and an additional strict selection procedure involving a betweenness ratio and an interaction score. Several candidate genes remained, which are deemed to be related to two different levels of cancer. The analyses confirmed our assertions that some have the potential to contribute to the tumorigenesis process on multiple levels. PMID- 27412433 TI - Nematodospora anomalae sp. nov., a novel and D-xylose-fermenting yeast species in the Lodderomyces clade. AB - Three strains of a novel species of ascomycetous yeast were isolated from the beetle species Anomala corpulenta (Scarabaeoidea) collected from the Baotianman and Funiu Mountains of China. These strains produced conjugated asci with a single coiled ascospore. Phylogenetic analysis of the combined sequences of the D1/D2 domains of the large subunit rRNA gene and internal transcribed spacer regions demonstrated that the three strains were closely related to Nematodospora valgi and an undescribed yeast strain, 13Y231. The novel strains could be differentiated from N. valgi CBS 12562T by a 1.6 % sequence divergence (9 substitutions) and from the undescribed yeast strain, 13Y231, by a 1.1 % sequence divergence (6 substitutions) in the D1/D2 sequences. The ITS sequences of these strains displayed more than 4.1 % sequence divergence (12-22 substitutions and 7 8 gaps) from their two closest relatives. Interestingly, all the three strains could ferment d-xylose to ethanol effectively, a rare property among members of the Lodderomyces clade. Therefore, a novel yeast species, Nematodosporaanomalae sp. nov., is proposed to accommodate these strains. The type strain of N.anomalae sp. nov. is NYNU 14914T (=CICC 33059T=CBS 13927T). The MycoBank number is MB 816795. PMID- 27412434 TI - Dramatic vascular compression by tension pneumoperitoneum. PMID- 27412435 TI - Unanswered questions about VTE prophylaxis in critically ill obese patients. PMID- 27412436 TI - Neoadjuvant treatment of rectal cancer: where are we now? PMID- 27412438 TI - Shear bond strength of composite resin bonded to preformed metal crowns for primary molars using a universal adhesive and two different surface treatments: an in vitro study. AB - AIM: This was to determine the shear bond strength of composite resin bonded to preformed metal crowns with a new adhesive. Buccal surfaces of the crowns were roughened by two different methods to increase retention. METHOD: Typodont mandibular second primary molars (38) were divided into two groups (19 per group). Preformed metal crowns were cemented to the teeth with glass-ionomer cement. To enhance retention, buccal surfaces of the crowns in group I were roughened with cross-cut carbide burs (SS White #56); crowns in group II were sandblasted (aluminium oxide, 50 um). Scotchbond Universal Adhesive (3 M-ESPE) was used to bond composite resin to the crowns. A universal testing machine tested the maximum shearing force withstood by the veneered composite surfaces. RESULTS: Sandblasted crowns demonstrated significantly higher resistance (p = 0.001) to shearing force (324.4 N) than did the crowns that were roughened with a bur (234.2 N). CONCLUSION: Chairside veneering of composite resin to pretreated crowns could be a feasible, aesthetically pleasing, and an economical option in paediatric dentistry. PMID- 27412437 TI - Effect of dentifrice of varying fluoride concentration on surface microhardness of fluorosed enamel: an in vitro study. AB - AIM: To evaluate the effect of dentifrice with varying concentrations of fluoride on surface microhardness of fluorosed enamel as compared to a non-fluoridated dentifrice. STUDY DESIGN: In vitro, comparative type. METHOD: 60 enamel blocks with score-3 enamel fluorosis were randomly divided into three groups: Group I non-fluoridated dentifrice, Group II 1000-ppm fluoridated dentifrice and Group III 1400-ppm fluoridated dentifrice. After evaluating the baseline surface microhardness, samples from each group were brushed for 2 min, twice daily for a period of 21 days with 0.02 g of respective interventional agents as per protocol. Microhardness of the samples was re-evaluated at the end of 21 days. Statistical analysis was performed using paired t test, ANOVA and Kruskal-Wallis test. RESULTS: The surface microhardness within the group from the baseline to 21st day post intervention, showed a statistically significant increase in all three groups, hence indicating that all the three interventional agents used were effective against the fluorosed enamel surface. Intergroup comparison of the surface microhardness of fluorosed enamel from baseline to 21st day post intervention showed a statistically significant difference (p < 0.001) amongst the groups with Group III proving most effective followed by Group I and Group II. CONCLUSION: 1400-ppm fluoridated dentifrice is more effective as compared to 1000-ppm fluoridated dentifrice and non-fluoridated dentifrice in increasing the surface microhardness of fluorosed enamel. PMID- 27412439 TI - In vitro evaluation of the antimicrobial effects of different intracanal medications in necrotic immature teeth. AB - AIM: This was to assess the antimicrobial effectiveness of pastes used as intracanal medicaments against Enterococcus faecalis in necrotic immature teeth. METHOD: An agar-disc diffusion method over a period of 30 days was used. The following medications were analysed: triple antibiotic paste (TAP) I; double antibiotic paste (DAP) I; DAP I with calcium hydroxide; calcium hydroxide paste with saline solution 0.9 %; calcium hydroxide paste with chlorhexidine 2 % gel; DAP II; DAP II with zinc oxide; DAP II with calcium hydroxide; and saline solution 0.9 % as control. The diameters of the halos of inhibition (in mm) of tested medicaments were determined and analysed with one-way analysis of variance and Tukey's post hoc tests. RESULTS: TAP I (G1) was significantly more effective against E. faecalis, and showed the largest halo of inhibition during all the experiments. DAP groups (G2 and G6) also showed inhibiting bacterial growth with said inhibition remaining stable throughout the 30-day period. In contrast, G4 and G5 groups, in which Ca(OH)2 was added to saline and chlorhexidine, had no antibacterial effect. CONCLUSIONS: TAP and DAP showed better antibacterial efficacy and remained active for 30 days. Combination of Ca(OH)2 with antibiotics should be avoided, due to the possibility of antibiotic hydrolysis. PMID- 27412440 TI - Peripartum events and molar-incisor hypomineralisation (MIH) amongst young patients in southwest France. AB - AIM: This was to investigate the association of peripartum events with the occurrence of MIH. METHODS: This study, carried out between 2010 and 2011, was based on objective information noted in child health booklets on putative risk factors for MIH during the Peripartum period, aged between 6 to 28 years. The target population consisted of patients with MIH and a control group. Among the 849 patients examined by two calibrated paediatric dentists, 75 patients with MIH were recorded. These patients attended for consultation either at the teaching dental hospital of Bordeaux (France) or at a private dental practice (Bordeaux, France). Pearson's Chi-squared test was used and Odds ratios (OR) with 95 % test based confidence intervals (CI) were calculated. RESULTS: Correlations were observed between hypoxia during delivery and occurrence of MIH (OR = 6.1; CI = 1.7-21.85), and also between birth by caesarean section and MIH (OR = 2.9; CI = 1.2-6.9). There was no association between prematurity and MIH. CONCLUSIONS: Peripartum events such as hypoxia during birth or delivery by caesarean section are suggested to be risk factors for the occurrence of MIH in this population. PMID- 27412441 TI - MECHANISMS IN ENDOCRINOLOGY: Endogenous subclinical hypercortisolism and bone: a clinical review. AB - In recent years, the condition of subclinical hypercortisolism (SH) has become a topic of growing interest. This is due to the fact that SH prevalence is not negligible (0.8-2% in the general population) and that, although asymptomatic, this subtle cortisol excess is not harmless, being associated with an increased risk of complications, in particular of osteoporosis and fragility fractures. As specific symptoms of hypercortisolism are absent in SH, the SH diagnosis relies only on biochemical tests and it is a challenge for physicians. As a consequence, even the indications for the evaluation of bone involvement in SH patients are debatable and guidelines are not available. Finally, the relative importance of bone density, bone quality and glucocorticoid sensitivity in SH is a recent field of research. On the other hand, SH prevalence seems to be increased in osteoporotic patients, in whom a vertebral fracture may be the presenting symptom of an otherwise asymptomatic cortisol excess. Therefore, the issue of who and how to screen for SH among the osteoporotic patients is widely debated. The present review will summarize the available data regarding the bone turnover, bone mineral density, bone quality and risk of fracture in patients with endogenous SH. In addition, the role of the individual glucocorticoid sensitivity in SH related bone damage and the problem of diagnosing and managing the bone consequences of SH will be reviewed. Finally, the issue of suspecting and screening for SH patients with apparent primary osteoporosis will be addressed. PMID- 27412442 TI - The role of optical coherence tomography angiography in fundus vascular abnormalities. AB - BACKGROUND: To evaluate the role of optical coherence tomography angiography (OCTA) in observation of fundus vascular abnormalities. METHODS: Patients (n = 50, 10 in each group) with fundus disorders including branch retinal vein occlusion (BRVO), non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), exudative age-related macular degeneration (AMD), and polypoidal choroidal vasculopathy (PCV) were examined. They underwent imaging of OCTA and fluorescein angiography/indocyanine green angiography. The split spectrum amplitude-decorrelation angiography algorithm was employed to obtain angiography within a 6 * 6 mm scanning area at the posterior retina. Segmentation algorithm was used to obtain 2-dimensional images from arbitrary layers. The OCTA features were analyzed and compared with the findings of conventional angiography. The contralateral eyes of the patients with BRVO and the eyes of 20 healthy volunteers served as controls. RESULTS: OCTA showed precise images of normal and abnormal vasculature in the posterior retina and choroid by the given layers. Vascular abnormalities such as enlarged foveal avascular zone (FAZ), non perfusion area of retina, microaneurysm, retinal neovascularization, choroidal neovascularization (CNV), branching vascular network and polypoidal lesions in choroid were clearly displayed by OCTA. CONCLUSIONS: OCTA provided a better projection of vascular pathologies of the posterior retina and choroid and could determine the precise location of the vascular lesion. The noninvasive OCTA can benefit the diagnosis of vascular abnormalities in the posterior retina and choroid. PMID- 27412443 TI - Long-term outcome of patients with ANCA-associated vasculitis treated with plasma exchange: a retrospective, single-centre study. AB - BACKGROUND: Plasma exchange (PLEX) has been used routinely for treatment of severe renal vasculitis and/or alveolar haemorrhage (AH) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the long-term benefit of PLEX in AAV remains unclear. We aimed to describe the characteristics and outcomes of patients treated with PLEX in a single centre. METHODS: Patients with AAV were identified by performing a case review of medical records of 705 patients who received PLEX in a single tertiary referral centre between 2000 and 2010. Patient characteristics and outcomes were recorded. The Kaplan-Meier method, log-rank tests and Cox regression analysis were used for survival analyses. RESULTS: A total of 94 patients with AAV were identified (44 men, 50 women; median age 60 years, range 21-90 years; 52 proteinase 3-ANCA, 41 myeloperoxidase-ANCA and 1 ANCA-negative; 8 double-positive for ANCA and anti glomerular basement membrane; 93 newly diagnosed/1 relapse; 55 [58.5 %] required dialysis). The reasons for initiating PLEX therapy were severe renal involvement alone in 52 %, AH in 10 %, both renal involvement and AH in 35 %, and "other" in 3 %. The patients had 3-27 (median 7) PLEX sessions. At 3 months, 81 (86 %) of 94 were alive and 62 (66 %) of 94 were alive and dialysis-independent. The median follow-up was 41 months (minimum-maximum 0.5-137 months), when 56 (59.6 %) of 94 patients were alive and 47 (50 %) were dialysis-independent. The estimated overall survival rates were 75.3 % at 1 year and 61.1 % at 5 years. Patient survival decreased with increasing age at presentation (5-year survival 85 % for age <50 years, 64.4 % for ages 50-65 years, and 41 % for >65 years; p < 0.01 for comparison between all groups). Estimated renal survival rates were 65.5 % at 1 year and 43 % at 5 years. Renal survival was worse in patients aged >65 years than in the younger patients (5-year survival 25.1 % in patients >65 years vs. 50.8 % for those <=65 years, p < 0.01). The estimated renal survival was better in patients with higher Disease Extent Index (DEI) >6 than in patients with DEI <=6 (5-year survival 52.1 % vs. 39.4 %, p = 0.04), even though this was not confirmed in multivariate analysis. CONCLUSIONS: The mortality of patients presenting with severe manifestations of AAV remains high despite the use of PLEX. Older age at presentation is associated with worse overall and renal prognosis. PMID- 27412444 TI - Combination with antimicrobial peptide lyses improves loop-mediated isothermal amplification based method for Chlamydia trachomatis detection directly in urine sample. AB - BACKGROUND: Chlamydia trachomatis is an obligate intracellular human pathogen and is the most common cause of sexually transmitted diseases affecting both men and women. The pathogen can cause prostatitis and epididymitis in men. In women, cervicitis, pelvic inflammatory disease, ectopic pregnancy and acute or chronic pelvic pain are frequent complications. More than half of C. trachomatis-positive patients have minimal or no symptoms, providing an ongoing reservoir for the infection. The lack of sensitive large-scale applicable point- of- care (POC) tests for C. trachomatis detection makes it difficult to diagnose chlamydia infection efficiently in resource-limited environments. METHODS: A rapid and sensitive assay based on loop-mediated isothermal amplification method (LAMP) was combined with antimicrobial peptide lysis, which is able to detect at least 7 C. trachomatis pathogens per reaction directly from urine samples. RESULTS: Our study comprising 91 first-void urine samples showed that specificity of the assay is 100 % and sensitivity 73 % when using antimicrobial peptide lysis mix. Additionally we demonstrate that our assay does not give any cross-reactivity with 30 pathogen's DNA potentially present in the urine samples. Furthermore, the assay's novel approach does not require purification or extraction of DNA from clinical sample prior to amplification, so the need for specialized equipment is eliminated. CONCLUSIONS: The whole procedure is significantly less laborious, less time-consuming and consequently less expensive for early detection and identification of infectious disease. C. trachomatis specific LAMP assay is relatively simple to perform and could therefore be applied in numerous POC settings. PMID- 27412445 TI - Maternal feeding practices and fussy eating in toddlerhood: a discordant twin analysis. AB - BACKGROUND: Parental feeding practices are thought to play a causal role in shaping a child's fussiness; however, a child-responsive model suggests that feeding practices may develop in response to a child's emerging appetitive characteristics. We used a novel twin study design to test the hypothesis that mothers vary their feeding practices for twin children who differ in their 'food fussiness', in support of a child-responsive model. METHODS: Participants were mothers and their 16 month old twin children (n = 2026) from Gemini, a British twin birth cohort of children born in 2007. Standardized psychometric measures of maternal 'pressure to eat', 'restriction' and 'instrumental feeding', as well as child 'food fussiness', were completed by mothers. Within-family analyses examined if twin-pair differences in 'food fussiness' were associated with differences in feeding practices using linear regression models. In a subset of twins (n = 247 pairs) who were the most discordant (highest quartile) on 'food fussiness' (difference score >= .50), Paired Samples T-test were used to explore the magnitude of differences in feeding practices between twins. Between-family analyses used Complex Samples General Linear Models to examine associations between feeding practices and 'food fussiness'. RESULTS: Within-pair differences in 'food fussiness' were associated with differential 'pressure to eat' and 'instrumental feeding' (ps < .001), but not with 'restriction'. In the subset of twins most discordant on 'food fussiness', mothers used more pressure (p < .001) and food rewards (p < .05) with the fussier twin. Between-family analyses indicated that 'pressure to eat' and 'instrumental feeding' were positively associated with 'food fussiness', while 'restriction' was negatively associated with 'food fussiness' (ps < .001). CONCLUSIONS: Mothers appear to subtly adjust their feeding practices according to their perceptions of their toddler's emerging fussy eating behavior. Specifically, the fussier toddler is pressured more than their less fussy co-twin, and is more likely to be offered food rewards. Guiding parents on how to respond to fussy eating may be an important aspect of promoting feeding practices that encourage food acceptance. PMID- 27412446 TI - Novel antimicrobial peptide prevents C. rodentium infection in C57BL/6 mice by enhancing acid-induced pathogen killing. AB - Citrobacter rodentium is a Gram-negative, murine-specific enteric pathogen that infects epithelial cells in the colon. It is closely related to the clinically relevant human pathogen, enterohemorrhagic Escherichia coli (EHEC), a leading cause of haemorrhagic colitis and haemolytic uremic syndrome. We have previously reported that a novel antimicrobial peptide, wrwycr, compromises bacterial DNA repair and significantly reduces the survival of acid-stressed EHEC, suggesting an antimicrobial strategy for targeting the survival of ingested EHEC. This study examines the impact of peptide pretreatment on survival of the closely related murine pathogen, C. rodentium, before and after acid stress, using both in vitro and in vivo investigations. Peptide pretreatment of C. rodentium significantly and dramatically increases acid-stress-induced killing in a peptide-dose dependent and time-dependent manner. Reduction in survival rates after brief pretreatment with peptide (25-65 uM) followed by 1 h at pH 3.5 ranges from 6 to 8 log fold relative to untreated C. rodentium, with no detectable bacteria after 65 uM peptide-acid treatment. Using a C57BL/6 mouse model of infection, peptide pretreatment of C. rodentium with wrwycr prior to orogastric gavage eliminates evidence of infection based on C. rodentium colonization levels, faecal scores, colonic histology, faecal microbiome and visual observation of overall animal health. These findings provide compelling evidence for the role of the peptide wrwycr as a potential strategy to control the growth and colonization of enteric pathogens. PMID- 27412447 TI - Preoperative planning for implant placement with consideration of pelvic tilt in total hip arthroplasty: postoperative efficacy evaluation. AB - BACKGROUND: In total hip arthroplasty (THA), tilting of the pelvis alters the cup placement angles. Thus, the cup angles need to be planned with consideration of the effects of pelvic tilt. In the present study, we evaluated the efficacy of preoperative planning for implant placement with consideration of pelvic tilt in THA, and the accuracy of a CT-based computer navigation for implant positioning. METHODS: We examined 75 hips of 75 patients who underwent THA and were followed up for one year postoperatively. The patients were divided into three groups (anterior, intermediate, posterior tilt) according to their preoperative pelvic tilt. Preoperative planning for implant placement was made with consideration of pelvic tilt and a CT-based navigation was used to execute the preoperative planning. Cup inclination, cup anteversion, and combined anteversion (CA) in supine and standing positions were examined 1 year after THA. The accuracy of the computer navigation was also examined. RESULTS: Mean CA was 35.0 +/- 5.8 degrees in supine position and 39.3 +/- 5.7 degrees in standing position. CA did not differ among the three subgroups (anterior, intermediate, posterior tilt) in either supine or standing position, indicating implant placements to be equally effective. The desired CA (37.3 degrees ) was midway between those in supine and standing positions for each subgroup. Respective mean absolute errors between preoperative planning and postoperative CT measurement was 5.3 +/- 5.2 degrees for CA. CONCLUSION: We obtained favorable THA results with preoperative planning with consideration of pelvic tilt by demonstrating supine and standing CA to be unaffected by preoperative pelvic tilt one year postoperatively. Mean absolute error of CA between preoperative planning and postoperative measurement was 5 degrees with use of the CT-based navigation. PMID- 27412448 TI - Drug-based pain management in people with dementia after hip or pelvic fractures: a systematic review protocol. AB - BACKGROUND: Studies show that people with dementia do not receive the same amount of analgesia after a hip or pelvic fracture compared to those without cognitive impairment. However, there is no systematic review that shows to what extent and how drug-based pain management is performed for people with dementia following a hip or pelvic fracture. The aim of this systematic review is to identify studies addressing drug-based pain management for people with dementia who have had a hip or pelvic fracture for which they had either an operation or conservative treatment. We will analyse to what extent and how the drug-based pain treatment for people with dementia is performed across all settings and how it is assessed in the studies. METHODS: The development of this systematic review protocol was guided by the PRISMA-P requirements, which will be taken into consideration during the review procedure. MEDLINE, EMBASE, CINAHL, Web of Knowledge and ScienceDirect will be searched, using keywords such as "analgesia", "dementia", "cognitive impairment", "pain treatment", "hip fracture" or "pelvic fracture". Publications published up to January 2016 will be included. The data extraction and a content analysis will be carried out systematically, followed by a critical appraisal. DISCUSSION: This review will provide a valuable overview on the current evidence on drug-based pain management for PwD in all settings who were conservatively treated after a hip or pelvic fracture. The review may expose a need to enhance pain management for PwD. It may also provide motivation for healthcare providers and policymakers to give this topic their attention and to facilitate further research by considering aspects of care transitions in all settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037309. PMID- 27412449 TI - Analysis of the impact of the course of hydration on the mechanical properties of the annulus fibrosus of the intervertebral disc. AB - PURPOSE: The aim of this study was to determine the impact of free hydration on the mechanical parameters of the annulus fibrosus (AF) of the intervertebral disc (IVD), determined in a standard manner. Attention was also given to the hydration occurring in real time and geometric changes resulting from swelling of the AF. METHODS: Uniaxial tensile tests of multilayer samples of the AF with bone attachment were performed for two groups: samples subjected to 30 min of hydration prior to the mechanical test, and control samples, which were not subjected to additional hydration. RESULTS: As a result of hydration, the values of both the failure stress (sigma UTS) and the tensile modulus (E) were lower than in the control group. A decrease in these values was observed for the AF from both the anterior and posterior parts of the IVD. CONCLUSIONS: The tests showed a significant dependence of the determined mechanical parameters on the cross-sectional area. The larger the cross-sectional area, the lower the obtained value of stress. By contrast, the value of the stiffness coefficient is independent of the cross-sectional area. The differences in mechanical parameters are related mainly to water absorption into structures of the AF during hydration. This is confirmed by microscopic analysis of geometric dimensions of the AF during hydration conducted in real time. The greatest changes occurred in the radial direction, where the thickness increased by 2.05 mm, while in the axial direction the main change concerned an increase in height by 0.69 mm. There were negligible changes in the circumferential direction. PMID- 27412450 TI - Risk factors for CKD progression in Japanese patients: findings from the Chronic Kidney Disease Japan Cohort (CKD-JAC) study. AB - BACKGROUND: Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese patients with CKD who are less affected with coronary disease than Westerners. METHODS: A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria [Japanese; age 20-75 years; and estimated glomerular filtration rate (eGFR): 10-59 mL/min/1.73 m2]. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration. RESULTS: 2966 patients (female, 38.9 %; age, 60. 3 +/- 11.6 years) were enrolled. The incidence of the primary endpoint increased significantly (P < 0.0001) in concert with CKD stage at baseline. The multivariate Cox proportional hazards models revealed that elevated systolic blood pressure (SBP) [hazard ratio (HR) 1.203, 95 % confidence interval (CI) 1.099-1.318)] and increased albumin-to-creatinine ratio (UACR >= 1000 mg/g Cre; HR: 4.523; 95 % CI 3.098-6.604) at baseline were significantly associated (P < 0.0001, respectively) with the primary endpoint. CONCLUSIONS: Elevated SBP and increased UACR were risk factors that were significantly associated with CKD progression to ESRD in Japanese patients under nephrology care. UMIN clinical trial registry number: UMIN000020038. PMID- 27412451 TI - Comments on Strang et al. (2016): 'Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?'. PMID- 27412452 TI - Host plant affects the sexual attractiveness of the female white-spotted longicorn beetle, Anoplophora malasiaca. AB - Anoplophora malasiaca (Coleoptera: Cerambycidae) is a serious pest that destroys various landscape and crop trees in Japan. We evaluated the precopulatory responses of three different A. malasiaca populations collected from mandarin orange, willow and blueberry trees. Most of the males accepted mates from within the same host plant population as well as females from the willow and blueberry populations. However, significant number of males from the blueberry and willow populations rejected females from the mandarin orange population immediately after touching them with their antennae. Because all three of the female populations produced contact sex pheromones on their elytra, the females of the mandarin orange population were predicted to possess extra chemicals that repelled the males of the other two populations. beta-Elemene was identified as a key component that was only found in mandarin orange-fed females and induced a rejection response in willow-fed males. Our results represent the first example of a female-acquired repellent against conspecific males of different host plant populations, indicating that the host plant greatly affects the female's sexual attractiveness. PMID- 27412453 TI - Post-synthetic Spin-Labeling of RNA through Click Chemistry for PELDOR Measurements. AB - Site-directed spin labeling of RNA based on click chemistry is used in combination with pulsed electron-electron double resonance (PELDOR) to benchmark a nitroxide spin label, called here dU. We compare this approach with another established method that employs the rigid spin label Cm for RNA labeling. By using CD spectroscopy, thermal denaturation measurements, CW-EPR as well as PELDOR we analyzed and compared the influence of dU and Cm on a self complementary RNA duplex. Our results demonstrate that the conformational diversity of dU is significantly reduced near the freezing temperature of a phosphate buffer, resulting in strongly orientation-selective PELDOR time traces of the dU-labeled RNA duplex. PMID- 27412454 TI - 1-methylnicotinamide and its structural analog 1,4-dimethylpyridine for the prevention of cancer metastasis. AB - BACKGROUND: 1-methylnicotinamide (1-MNA), an endogenous metabolite of nicotinamide, has recently gained interest due to its anti-inflammatory and anti thrombotic activities linked to the COX-2/PGI2 pathway. Given the previously reported anti-metastatic activity of prostacyclin (PGI2), we aimed to assess the effects of 1-MNA and its structurally related analog, 1,4-dimethylpyridine (1,4 DMP), in the prevention of cancer metastasis. METHODS: All the studies on the anti-tumor and anti-metastatic activity of 1-MNA and 1,4-DMP were conducted using the model of murine mammary gland cancer (4T1) transplanted either orthotopically or intravenously into female BALB/c mouse. Additionally, the effect of the investigated molecules on cancer cell-induced angiogenesis was estimated using the matrigel plug assay utilizing 4T1 cells as a source of pro-angiogenic factors. RESULTS: Neither 1-MNA nor 1,4-DMP, when given in a monotherapy of metastatic cancer, influenced the growth of 4T1 primary tumors transplanted orthotopically; however, both compounds tended to inhibit 4T1 metastases formation in lungs of mice that were orthotopically or intravenously inoculated with 4T1 or 4T1-luc2-tdTomato cells, respectively. Additionally, while 1-MNA enhanced tumor vasculature formation and markedly increased PGI2 generation, 1,4 DMP did not have such an effect. The anti-metastatic activity of 1-MNA and 1,4 DMP was further confirmed when both agents were applied with a cytostatic drug in a combined treatment of 4T1 murine mammary gland cancer what resulted in up to 80 % diminution of lung metastases formation. CONCLUSIONS: The results of the studies presented below indicate that 1-MNA and its structural analog 1,4-DMP prevent metastasis and might be beneficially implemented into the treatment of metastatic breast cancer to ensure a comprehensive strategy of metastasis control. PMID- 27412455 TI - Long-Term Retrospective Analysis of Gene Therapy with Alipogene Tiparvovec and Its Effect on Lipoprotein Lipase Deficiency-Induced Pancreatitis. AB - Alipogene tiparvovec (Glybera) is a gene therapy product approved in Europe under the "exceptional circumstances" pathway as a treatment for lipoprotein lipase deficiency (LPLD), a rare genetic disease resulting in chylomicronemia and a concomitantly increased risk of acute and recurrent pancreatitis, with potentially lethal outcome. This retrospective study analyzed the frequency and severity of pancreatitis in 19 patients with LPLD up to 6 years after a single treatment with alipogene tiparvovec. An independent adjudication board of three pancreas experts, blinded to patient identification and to pre- or post-gene therapy period, performed a retrospective review of data extracted from the patients' medical records and categorized LPLD-related acute abdominal pain events requiring hospital visits and/or hospitalizations based on the adapted 2012 Atlanta diagnostic criteria for pancreatitis. Both entire disease time period data and data from an equal time period before and after gene therapy were analyzed. Events with available medical record information meeting the Atlanta diagnostic criteria were categorized as definite pancreatitis; events treated as pancreatitis but with variable levels of laboratory and imaging data were categorized as probable pancreatitis or acute abdominal pain events. A reduction of approximately 50% was observed in all three categories of the adjudicated post gene therapy events. Notably, no severe pancreatitis and only one intensive care unit admission was observed in the post-alipogene tiparvovec period. However, important inter- and intraindividual variations in the pre- and post-gene therapy incidence of events were observed. There was no relationship between the posttreatment incidence of events and the number of LPL gene copies injected, the administration of immunosuppressive regimen or the percent triglyceride decrease achieved at 12 weeks (primary end point in the prospective clinical studies). Although a causal relationship cannot be established and despite the limited number of individuals evaluated, results from this long-term analysis suggest that alipogene tiparvovec was associated with a lower frequency and severity of pancreatitis events, and a consequent overall reduction in health care resource use up to 6 years posttreatment. PMID- 27412456 TI - Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 1. High abundance proteins, acute phase proteins and peptidomics. AB - A peptidomic investigation of milk from an experimental model of Streptococcus uberis mastitis in dairy cows has incorporated a study of milk high abundance and acute phase (APP) proteins as well as analysis of low molecular weight peptide biomarkers. Intramammary infection (IMI) with S. uberis caused a shift in abundance from caseins, beta-lactoglobulin and alpha-lactalbumin to albumin, lactoferrin and IgG with the increase in lactoferrin occurring last. The APP response of haptoglobin, mammary associated serum amyloid A3 and C-reactive protein occurred between 30-48 hours post challenge with peak concentrations of APPs at 72-96 hours post challenge and declined thereafter at a rate resembling the fall in bacterial count rather than the somatic cell count. A peptide biomarker panel for IMI based on capillary electrophoresis and mass spectrometry was developed. It comprised 77 identified peptides (IMI77) composed mainly of casein derived peptides but also including peptides of glycosylation dependent cell adhesion molecule and serum amyloid A. The panel had a biomarker classification score that increased from 36 hour to 81 hour post challenge, significantly differentiating infected from non-infected milk, thus suggesting potential as a peptide biomarker panel of bovine mastitis and specifically that of S. uberis origin. The use of omic technology has shown a multifactorial cross system reaction in high and low abundance proteins and their peptide derivatives with changes of over a thousand fold in analyte levels in response to S. uberis infection. PMID- 27412457 TI - DAWN2 shines more light on the psychological burden of living with diabetes and on the correlates of quality psychological care. PMID- 27412459 TI - Protocol for the End-of-Life Social Action Study (ELSA): a randomised wait-list controlled trial and embedded qualitative case study evaluation assessing the causal impact of social action befriending services on end of life experience. AB - BACKGROUND: Compassionate support at the end of life should not be the responsibility of health and social care professionals alone and requires a response from the wider community. Volunteers, as community members, are a critical part of many end-of-life care services. The impact of their services on important outcomes such as quality of life is currently poorly understood. The purpose of this study is to evaluate a series of social action initiatives which use volunteers to deliver befriending services to people anticipated to be in their last year of life. The aim is to determine if receiving care from a social action volunteer befriending service plus usual care significantly improves quality of life in the last year of life. METHODS/DESIGN: The research questions will be addressed through a wait-list randomised controlled trial (WLRCT) and qualitative case study evaluation across 12 sites in England. Participants will be randomly allocated to either receive the social action volunteer befriending service straight away or receive the intervention after a four week wait (wait list arm). The impact of the intervention on end-of-life experience (quality of life as primary outcome, loneliness, social support) will be measured. Repeated assessments will be carried out at baseline and weeks 4 and 8 for the intervention arm and weeks 4, 8 and 12 for the wait-list arm. For selected sites case study evaluation will include interviews, observation and documentary analysis to understand the mechanisms underpinning any found impact. DISCUSSION: This study will address the need to both provide services which use social action models to support end-of-life care in community settings, and to robustly evaluate these models to determine if they influence the experience of end-of life care. Such services could work to reduce isolation, help meet emotional needs and maintain a sense of connectedness to the community. ISRCTN 12929812 Registered 20.5.15. PMID- 27412458 TI - Gold silver alloy nanoparticles (GSAN): an imaging probe for breast cancer screening with dual-energy mammography or computed tomography. AB - Earlier detection of breast cancer reduces mortality from this disease. As a result, the development of better screening techniques is a topic of intense interest. Contrast-enhanced dual-energy mammography (DEM) is a novel technique that has improved sensitivity for cancer detection. However, the development of contrast agents for this technique is in its infancy. We herein report gold silver alloy nanoparticles (GSAN) that have potent DEM contrast properties and improved biocompatibility. GSAN formulations containing a range of gold : silver ratios and capped with m-PEG were synthesized and characterized using various analytical methods. DEM and computed tomography (CT) phantom imaging showed that GSAN produced robust contrast that was comparable to silver alone. Cell viability, reactive oxygen species generation and DNA damage results revealed that the formulations with 30% or higher gold content are cytocompatible to Hep G2 and J774A.1 cells. In vivo imaging was performed in mice with and without breast tumors. The results showed that GSAN produce strong DEM and CT contrast and accumulated in tumors. Furthermore, both in vivo imaging and ex vivo analysis indicated the excretion of GSAN via both urine and feces. In summary, GSAN produce strong DEM and CT contrast, and has potential for both blood pool imaging and for breast cancer screening. PMID- 27412460 TI - A novel fusion partner for enhanced secretion of recombinant proteins in Saccharomyces cerevisiae. AB - Expressing proteins with fusion partners improves yield and simplifies the purification process. We developed a novel fusion partner to improve the secretion of heterologous proteins that are otherwise poorly excreted in yeast. The VOA1 (YGR106C) gene of Saccharomyces cerevisiae encodes a subunit of vacuolar ATPase. We found that C-terminally truncated Voa1p was highly secreted into the culture medium, even when fused with rarely secreted heterologous proteins such as human interleukin-2 (hIL-2). Deletion mapping of C-terminally truncated Voa1p, identified a hydrophilic 28-amino acid peptide (HL peptide) that was responsible for the enhanced secretion of target protein. A purification tag and a protease cleavage site were added to use HL peptide as a multi-purpose fusion partner. The utility of this system was tested via the expression and purification of various heterologous proteins. In many cases, the yield of target proteins fused with the peptide was significantly increased, and fusion proteins could be directly purified with affinity chromatography. The fusion partner was removed by in vitro processing, and intact proteins were purified by re-application of samples to affinity chromatography. PMID- 27412461 TI - Generation of new compounds through unbalanced transcription of landomycin A cluster. AB - The biosynthetically well-studied landomycin A cluster has been used to demonstrate the unbalancing of gene transcription as an efficient method for the generation of new compounds. Landomycin A structural genes were decoupled from the native regulators LanI and LanK and placed under the control of a single synthetic promoter and expressed in a heterologous host Streptomyces albus J1074. In contrast to their native quantitative and temporal regulation, these genes were transcribed as a single polycistronic mRNA leading to the production of four novel and two known compounds. No glycosylated landomycins were detected though the entire biosynthetic cluster was transcribed, showing the crucial role of the balanced gene expression for the production of landomycin A. Two new compounds, fridamycin F and G, isolated in this study were shown to originate from the interplay between the expressed biosynthetic pathway and metabolic network of the heterologous host. Structure activity studies of the isolated compounds as well as results of transcriptome sequencing are discussed in this article. PMID- 27412462 TI - A new extracellular von Willebrand A domain-containing protein is involved in silver uptake in Microcystis aeruginosa exposed to silver nanoparticles. AB - Silver nanoparticles (AgNPs) can be toxic for cyanobacteria when present at low nanomolar concentrations, but the molecular mechanisms whereby AgNPs (or free Ag(+) released from AgNPs) interact with these prokaryotic algal cells remain elusive. Here, we studied Ag uptake mechanisms in the prokaryotic cyanobacterium Microcystis aeruginosa exposed to AgNPs by measuring growth inhibition in the absence or presence of high-affinity Ag-binding ligands and by genetic transformation of E. coli with a protein predicted to be involved in Ag uptake. We discovered a new von Willebrand A (vWA) domain-containing protein in M. aeruginosa that mediates Ag uptake from AgNPs when expressed in E. coli. This new Ag transport protein, which is absent in eukaryotic algae, is a potential candidate explaining the higher AgNPs toxicity in cyanobacteria such as M. aeruginosa than that in eukaryotic algae. The present study provides new insights on Ag uptake mechanisms in the prokaryotic algae M. aeruginosa. PMID- 27412463 TI - Enhanced production of nargenicin A1 and creation of a novel derivative using a synthetic biology platform. AB - Nargenicin A1, an antibacterial produced by Nocardia sp. CS682 (KCTC 11297BP), demonstrates effective activity against various Gram-positive bacteria. Hence, we attempted to enhance nargenicin A1 production by utilizing the cumulative effect of synthetic biology, metabolic engineering and statistical media optimization strategies. To facilitate the modular assembly of multiple genes for genetic engineering in Nocardia sp. CS682, we constructed a set of multi-monocistronic vectors, pNV18L1 and pNV18L2 containing hybrid promoter (derived from ermE* and promoter region of neo r ), ribosome binding sites (RBS), and restriction sites for cloning, so that each cloned gene was under its own promoter and RBS. The multi-monocistronic vector, pNV18L2 containing transcriptional terminator showed better efficiency in reporter gene assay. Thus, multiple genes involved in the biogenesis of pyrrole moiety (ngnN2, ngnN3, ngnN4, and ngnN5 from Nocardia sp. CS682), glucose utilization (glf and glk from Zymomonas mobilis), and malonyl-CoA synthesis (accA2 and accBE from Streptomyces coelicolor A3 (2)), were cloned in pNV18L2. Further statistical optimization of specific precursors (proline and glucose) and their feeding time led to ~84.9 mg/L nargenicin from Nocardia sp. GAP, which is ~24-fold higher than Nocardia sp. CS682 (without feeding). Furthermore, pikC from Streptomyces venezuelae was expressed to generate Nocardia sp. PikC. Nargenicin A1 acid was characterized as novel derivative of nargenicin A1 produced from Nocardia sp. PikC by mass spectrometry (MS) and nuclear magnetic resonance (NMR) analyses. We also performed comparative analysis of the anticancer and antibacterial activities of nargenicin A1 and nargenicin A1 acid, which showed a reduction in antibacterial potential for nargenicin A1 acid. Thus, the development of an efficient synthetic biological platform provided new avenues for enhancing or structurally diversifying nargenicin A1 by means of pathway designing and engineering. PMID- 27412464 TI - Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study. AB - BACKGROUND: TAS-102 (trifluridine and tipiracil hydrochloride; a novel combination oral nucleoside anti-tumor agent) has recently received regulatory approval for patients with refractory metastatic colorectal cancer (mCRC). Internal review of data at a single-institution showed a trend towards better overall survival (OS) for patients who experienced chemotherapy-induced neutropenia at 1-month (CIN-1-month). To explore this finding further, a cohort study was designed based on outcome data from three centers in United States and one from Japan. METHODS: CIN-1-month after starting TAS-102 was defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 as a neutrophil count decrease of >= grade 2 (absolute neutrophil count < 1500/mm(3)). Patients had confirmed mCRC that was refractory to standard therapies. Patient demographics and clinical characteristics were compared between patients with CIN 1-month (CIN-1-month positive) versus those who did not have CIN-1-month (CIN-1 month negative); with the median progression-free survival (PFS) and OS were calculated using the Kaplan-Meier method, and differences evaluated using the Log rank test. RESULTS: Our cohort study had a total of 149 patients with data regarding their neutrophil assessment at 1-month mark. Patients who developed >= grade 2 CIN-1-month had a both longer PFS (median 3.0 months versus 2.4 months; Log-rank P-value = 0.01), as well as OS (14.0 versus 5.6 months; Log-rank P-value < 0.0001). Only CIN-1-month (adjusted HR: 0.21 (95 % CI: 0.11-0.38) and higher baseline CEA levels (adjusted HR: 2.00 (95 % CI: 1.22-3.35) were noted to be independent predictors of OS. Furthermore, the CIN-1-month was noted to be a statistically significantly predictor of OS over a wide range of cutoffs. CONCLUSIONS: Our observations are novel and hypothesis generating. Neutropenia after starting TAS-102 was associated with better prognosis in patients with refractory mCRC. It can be postulated that the dosage of TAS-102 potentially may need to be increased to achieve better outcomes in patients not experiencing any neutropenia. Further pharmacologic investigations should help elucidate these issues. PMID- 27412466 TI - Linshom respiratory monitoring device: a novel temperature-based respiratory monitor. AB - PURPOSE: We sought to develop a temperature-based respiratory instrument to measure respiration noninvasively outside critical care settings. METHOD: Respiratory temperature profiles were recorded using a temperature-based noninvasive instrument comprised of three rapid responding medical-grade thermistors-two in close proximity to the mouth/nose (sensors) and one remote to the airway (reference). The effect of the gas flow rate on the amplitude of the tracings was determined. The temperature-based instrument, the Linshom Respiratory Monitoring Device (LRMD) was mounted to a face mask and positioned on a mannequin face. Respiratory rates of 5-40 breaths.min(-1) were then delivered to the mannequin face in random order using artificial bellows (IngMar Lung Model). Data from the sensors were collected and compared with the bellows rates using least squares linear regression and coefficient of determination. The investigators breathed at fixed rates of 0-60 breaths.min(-1) in synchrony with a metronome as their respiratory temperature profiles were recorded from sensors mounted to either a face mask or nasal prongs. The recordings were compared with a contemporaneously recorded sidestream capnogram from a CARESCAPE GEB450 Monitor. The extracted respiratory rates from the LRMD tracings and capnograms were compared using linear regression with a coefficient of determination and a Bland-Altman plot. RESULTS: The amplitude of the sensor tracings was independent of the oxygen flow rate. Respiratory rates from the new temperature-based sensor were synchronous and correlated identically with both the artificial bellows (r(2) = 0.9997) and the capnometer mounted to both the face mask and nasal prongs (r(2) = 0.99; bias = -0.17; 95% confidence interval, -2.15 to 1.8). CONCLUSIONS: Respiratory rates using the LRMD, a novel temperature-based respiratory instrument, were consistent with those using capnometry. PMID- 27412465 TI - Effects of anesthetics on early postoperative cognitive outcome and intraoperative cerebral oxygen balance in patients undergoing lung surgery: a randomized clinical trial. AB - PURPOSE: One-lung ventilation (OLV) may impair cerebral oxygen balance and induce postoperative cognitive dysfunction (POCD). It is unclear whether the type of anesthetic influences the incidence of POCD in patients undergoing OLV. This prospective study compared the incidence of POCD and intraoperative cerebral oxygen desaturation in OLV patients anesthetized with propofol vs sevoflurane during lung surgery. METHODS: There were 148 participants enrolled in this study and randomized equally to either the propofol or the sevoflurane group. Anesthesia was maintained with either propofol or sevoflurane combined in both groups with fentanyl and epidural anesthesia. Regional cerebral oxygen saturation (rSO2), jugular bulb venous oxygen saturation (SjO2), and the incidence of cerebral oxygen desaturation (rSO2 or SjO2 < 50% or rSO2 < 80% of baseline) were measured during anesthesia. Cognitive function was assessed using seven neurocognitive tests two days preoperatively, five days postoperatively (primary outcome), and three months postoperatively. Bivariable and multivariable regression analyses were conducted to identify factors associated with POCD. RESULTS: Rates of POCD did not differ statistically between groups five days postoperatively (propofol, 16/72 patients; sevoflurane, 24/72 patients; RR, 0.67; 95% CI, 0.39 to 1.15; P = 0.14) or three months postoperatively (propofol, 9/60 patients; sevoflurane, 12/58 patients; RR, 0.73; 95% CI, 0.33 to 1.59; P = 0.42). Only three subjects per group showed intraoperative cerebral oxygen desaturation. Multivariable regression analysis revealed older age as an independent predictor of POCD. CONCLUSIONS: No statistically significant difference in the incidence of POCD could be detected between the sevoflurane and propofol anesthesia groups. Postoperative cognitive dysfunction was relatively frequent following OLV in both groups. ( REGISTRATION NUMBER: UMIN 000002826). PMID- 27412468 TI - Corrigendum. PMID- 27412467 TI - Are Chinese Correlative Conjunctions Psychologically Real? An Investigation of the Combination Frequency Effect. AB - The present study used an online grammaticality judgment task to examine whether Chinese discontinuous correlative conjunctions are psychologically real in mental lexicon. High- and low-frequency discontinuous correlative conjunctions were compared with random combinations differing in combination frequencies but matched for constituent word frequency. Forty graduate students participated in the study. Results showed that responses were faster and more accurate for high frequency correlative conjunctions than low-frequency ones, but the effects were absent for random combinations. The results indicate that Chinese discontinuous correlative conjunctions have psychological reality in mental lexicon in addition to the representation of their constituent words, and that grammatical functions of correlative conjunctions may be a critical factor for the formation of such holistic representations. PMID- 27412469 TI - Involvement of PI3K/Akt/FoxO3a and PKA/CREB Signaling Pathways in the Protective Effect of Fluoxetine Against Corticosterone-Induced Cytotoxicity in PC12 Cells. AB - The selective serotonin reuptake inhibitor fluoxetine is neuroprotective in several brain injury models. It is commonly used to treat major depressive disorder and related conditions, but its mechanism of action remains incompletely understood. Activation of the phosphatidylinositol-3-kinase/protein kinase B/forkhead box O3a (PI3K/Akt/FoxO3a) and protein kinase A/cAMP-response element binding protein (PKA/CREB) signaling pathways has been strongly implicated in the pathogenesis of depression and might be the downstream target of fluoxetine. Here, we used PC12 cells exposed to corticosterone (CORT) to study the neuroprotective effects of fluoxetine and the involvement of the PI3K/Akt/FoxO3a and PKA/CREB signaling pathways. Our results show that CORT reduced PC12 cells viability by 70 %, and that fluoxetine showed a concentration-dependent neuroprotective effect. Neuroprotective effects of fluoxetine were abolished by inhibition of PI3K, Akt, and PKA using LY294002, KRX-0401, and H89, respectively. Treatment of PC12 cells with fluoxetine resulted in increased phosphorylation of Akt, FoxO3a, and CREB. Fluoxetine also dose-dependently rescued the phosphorylation levels of Akt, FoxO3a, and CREB, following administration of CORT (from 99 to 110, 56 to 170, 80 to 170 %, respectively). In addition, inhibition of PKA and PI3K/Akt resulted in decreased levels of p-CREB, p-Akt, and p-FoxO3a in the presence of fluoxetine. Furthermore, fluoxetine reversed CORT-induced upregulation of p53-upregulated modulator of apoptosis (Puma) and Bcl-2 interacting mediator of cell death (Bim) via the PI3K/Akt/FoxO3a signaling pathway. H89 treatment reversed the effect of fluoxetine on the mRNA level of brain-derived neurotrophic factor, which was decreased in the presence of CORT. Our data indicate that fluoxetine elicited neuroprotection toward CORT-induced cell death that involves dual regulation from PI3K/Akt/FoxO3a and PKA/CREB pathways. PMID- 27412470 TI - Determinants of post-stroke cognitive impairment: analysis from VISTA. AB - BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs commonly and is linked with development of dementia. We investigated the relationship between demographic, clinical and stroke symptoms at stroke onset and the presence of PSCI at 1 and 3 years after stroke. METHODS: We accessed anonymized data from the Virtual International Stroke Trial Archive (VISTA), including demographic and clinical variables. Post-stroke cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of <=26. We assessed univariate relationships between baseline stroke symptoms and PSCI at 1 and 3 years following stroke, retaining the significant and relevant clinical factors as covariates in a final adjusted logistic regression model. RESULTS: We analysed data on 5435 patients with recent (median 33 days) stroke or transient ischaemic attack (TIA). Mean (+/ SD) age was 62.6 (+/-12.6) years; 3476 (65%) patients were male. Follow-up data were available for 2270 and 1294 patients at 1 and 3 years, respectively. At 1 year, 781 (34%) patients had MMSE<=26; at 3 years, 391 (30%) had MMSE<=26. After adjusting for age, stroke severity, hypertension, diabetes and type of qualifying event, initial stroke impairment (leg paralysis) was associated with increased rate of PSCI at 1 year (OR=1.62; 95% CI=1.20-2.20) and at 3 years (OR=1.95; 95% CI=1.23-3.09). Associations were consistent on subgroup analysis restricted to ischaemic stroke and transient ischaemic attack (N=4992). CONCLUSIONS: Besides well-known determinants of PSCI such as age, stroke severity and the presence of vascular risk factors, also leg paralysis is associated with subsequent of PSCI up to 3 years after stroke. PMID- 27412471 TI - The nephroprotection exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy. AB - We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate-induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)-injection. Curcumin prevented maleate induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity. Maleate-induced oxidative stress by increasing the nicotinamide-adenine dinucleotide phosphate oxidase 4 (NOX4) and mitochondrial complex I-dependent superoxide anion (O2 *- ) production, formation of malondialdehyde (MDA)- and 3-nitrotyrosine (3-NT) protein adducts and protein carbonylation and decreased GSH/GSSG ratio. Curcumin treatment ameliorated all the above-described changes. The maleate-induced epithelial damage, evaluated by claudin-2 and occludin expressions, was ameliorated by curcumin. It was found that maleate-induced oxidative stress promoted mitochondrial fission, evaluated by dynamin-related protein (Drp) 1 and fission (Fis) 1 expressions and by electron-microscopy, and autophagy, evaluated by phospho-threonine 389 from p70 ribosomal protein S6 kinase (p-Thr 389 p70S6K), beclin 1, microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate (LC3-II), autophagy-related gene 5 and 12 (Atg5-Atg12) complex, p62, and lysosomal-associated membrane protein (LAMP)-2 expressions in isolated proximal tubules and by electron-microscopy and LC-3 immunolabelling. Curcumin treatment ameliorated these changes. Moreover, curcumin alone induced autophagy in proximal tubules. These data suggest that the nephroprotective effect exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy. (c) 2016 BioFactors, 42(6):686-702, 2016. PMID- 27412472 TI - Gold-Nanoparticle-Based Colorimetric Sensor Array for Discrimination of Organophosphate Pesticides. AB - There is a growing interest in developing high-performance sensors monitoring organophosphate pesticides, primarily due to their broad usage and harmful effects on mammals. In the present study, a colorimetric sensor array consisting of citrate-capped 13 nm gold nanoparticles (AuNPs) has been proposed for the detection and discrimination of several organophosphate pesticides (OPs). The aggregation-induced spectral changes of AuNPs upon OP addition has been analyzed with pattern recognition techniques, including hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA). In addition, the proposed sensor array has the capability to identify individual OPs or mixtures of them in real samples. PMID- 27412473 TI - The role of AMPK in cardiomyocyte health and survival. AB - Cellular energy homeostasis is a fundamental process that governs the overall health of the cell and is paramount to cell survival. Central to this is the control of ATP generation and utilization, which is regulated by a complex myriad of enzymatic reactions controlling cellular metabolism. In the cardiomyocyte, ATP generated from substrate catabolism is used for numerous cellular processes including maintaining ionic homeostasis, cell repair, protein synthesis and turnover, organelle turnover, and contractile function. In many instances, cardiovascular disease is associated with impaired cardiac energetics and thus the signalling that regulates pathways involved in cardiomyocyte metabolism may be potential targets for pharmacotherapy designed to help treat cardiovascular disease. An important regulator of cardiomyocyte energy homeostasis is adenosine monophosphate-activated protein kinase (AMPK). AMPK is a serine-threonine kinase that functions primarily as a metabolic sensor to coordinate anabolic and catabolic activities in the cell via the phosphorylation of multiple proteins involved in metabolic pathways. In addition to the direct role that AMPK plays in the regulation of cardiomyocyte metabolism, AMPK can also either directly or indirectly influence other cellular processes such as regulating mitochondrial function, post-translation acetylation, autophagy, mitophagy, endoplasmic reticulum stress, and apoptosis. Thus, AMPK is implicated in the control of a wide variety of cellular processes that can influence cardiomyocyte health and survival. In this review, we will discuss the important role that AMPK plays in regulating cardiac metabolism, as well as the additional cellular processes that may contribute to cardiomyocyte function and survival in the healthy and the diseased heart. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan. F.C. Glatz. PMID- 27412474 TI - Does the presence of mitral regurgitation strengthen or weaken the indication for cardiac resynchronization therapy? PMID- 27412475 TI - Enabling tomorrow's doctors to address obesity in a GP consultation: an action research project. AB - Obesity is a leading risk factor for morbidity and mortality, however, guidelines for prevention and management are relatively recently established. Little is known about what needs to be in place to put these into practice. This research provides an insight into how senior medical students consult with obese patients in general practice, the range of their learning needs, and the impact of various educational strategies that aim to bring their practice closer to current evidence-based guidelines. It centres on a series of compulsory but formative reflective case studies written by final year students at one large medical school on their GP rotation as they consult independently with obese patients with 'next room' GP tutor support. Analysis of these case studies was used to inform a three-year educational action research project. By systematically identifying and addressing learning needs, including barriers and enablers to best practice, we have demonstrated how senior medical students, and their GP tutors, can acquire the role legitimacy and role competency required for effective practice. PMID- 27412476 TI - [Quality of the Spanish Clinical Guidelines about Alzheimer's Disease and others Dementias]. AB - BACKGROUND: The care of patients with Alzheimer's disease and other dementias has become a priority for healthcare systems. This is evidenced by the increasing number of clinical practice guidelines (CPG) developed in our country aimed to help professionals in making health decisions. The aim of our study was to evaluate the quality of the Spanish CPG on Alzheimer's disease and other dementias using the AGREE II instrument. METHODS: Nine GPC were selected according to the inclusion criteria: Full GPC available; aimed to healthcare professionals; and published between 2002-2013. Two reviewers independently assessed the quality of the guides through the AGREE II instrument, in order to assess the methodological rigor and transparency of the GPC. RESULTS: 88.8% of the guides scored a very poor quality editorial independence. Respect to rigor in the development and clarity of presentation, 77.7% also scored very low quality. There is a guide that stands out for a score above 50% in all domains of the instrument. CONCLUSIONS: The worst scored domains were Editorial independence, Rigor in the development and Applicability, in this order. The highest rated domains were Scope and Objectives and Clarity of Presentation. The guideline of the Ministry of Health, Social Policy and Equality is the best, obtaining a score above 50% in all domains. Overall, the quality of the 9 guidelines evaluated is low or very low, only two of them score as good overall quality. PMID- 27412477 TI - Pre-Feedback Risk Expectancies and Reception of Low-Risk Health Feedback: Absolute and Comparative Lack of Reassurance. AB - BACKGROUND: Personalised health-risk assessment is one of the most common components of health promotion programs. Previous research on responses to health risk feedback has commonly focused on the reception of bad news (high-risk feedback). The reception of low-risk feedback has been comparably neglected since it is assumed that good news is reassuring and readily received. However, field studies suggest mixed responses to low-risk health feedback. Accordingly, we examine whether pre-feedback risk expectancies can mitigate the reassuring effects of good news. METHODS: In two studies (N = 187, N = 565), after assessing pre-feedback risk expectancies, participants received low-risk personalised feedback about their own risk of developing (the fictitious) Tucson Chronic Fatigue Syndrome (TCFS). Study 2 also included peer TCFS risk status feedback. Afterwards, self- and peer-related risk perception for TCFS was assessed. RESULTS: In both studies, participants who expected to be at high risk but received good news (unexpected low-risk feedback) showed absolute lack of reassurance. Specifically, they felt at significantly greater TCFS risk than participants who received expected good news. Moreover, the unexpected low-risk group even believed that their risk was as high as (Study 1) or higher (Study 2) than that of their peers (comparative lack of reassurance). CONCLUSION: Results support the notion that high pre-feedback risk expectancies can mitigate absolute and comparative reassuring effects of good news. PMID- 27412478 TI - Epileptic seizure in primary intracranial sarcoma: a case report and literature review. AB - PURPOSE: The aim of this study is to describe epileptic seizures in patients with primary intracranial sarcomas. METHODS: We report a 17-year-old girl diagnosed with primary high-grade intracranial sarcoma with initial clinical manifestation of nonconvulsive status epilepticus. Literature reports between 2000 and 2014, relevant to primary intracranial sarcomas in children, were reviewed. The clinical presentations and neurological outcomes were analyzed. RESULTS: Eleven of 29cases (38 %), 8 males and 3 females, who exhibited epileptic seizures as one of the initial symptoms and diagnosed with primary intracranial sarcomas were collected. The median age of disease onset was 5 years. The two most common seizure types were generalized seizures (45 %) and status epilepticus (36 %). Nine of 11 patients (82 %) had tumor growth involving the frontal lobe. Nine cases had the median duration of follow-up 1.7 years, of which 6 cases showed tumor recurrence and 3 cases died during the period of follow-up. CONCLUSIONS: Epileptic seizures as one of the clinical manifestations are uncommon. The two most common seizure types were generalized seizures and status epilepticus. The most frequent location of primary intracranial sarcoma-related seizures was the frontal lobe. The clinical outcome varied. PMID- 27412479 TI - Microparticles reveal cell activation during IVF - a possible early marker of a prothrombotic state during the first trimester. AB - Cell-derived microparticles (MPs) are known to be elevated in a number of diseases related to arterial and venous thromboembolism (VTE), such as acute myocardial infarction, VTE (deep-vein thrombosis and pulmonary embolism) and peripheral arterial disease. IVF-associated pregnancies have previously been shown to be associated with an increased incidence of VTE, mechanisms behind being unknown and sparsely studied. Our objective was to assess cell activation during IVF through analysis of MP levels and phenotype following ovarian stimulation. Thirty-one women undergoing IVF were included and blood samples were collected at down regulation of oestrogen and at high level stimulation with 10- to 100-fold increased endogenous oestrogen levels. MPs were analysed by flow cytometry and phenotyped according to size and protein expression. We found that overall phosphatidylserine positive platelet-, endothelial- and monocyte-derived MPs significantly increased following ovarian stimulation with increased levels of platelet activation markers CD40 ligand and P-selectin. Furthermore, there was an increase in endothelial-derived MPs exposing activation marker E-selectin and monocyte-derived MPs, while neutrophil-derived MPs decreased slightly. In conclusion we found a major increase in MPs and markers indicating cell activation in parallel with the profound oestrogen boost during IVF. To assess whether these changes in MPs are associated with thromboembolic events requires extended longitudinal studies. PMID- 27412480 TI - Phthalate metabolites in the European eel (Anguilla anguilla) from Mediterranean coastal lagoons. AB - The levels and fate of phthalate metabolites have been poorly evaluated in fish, despite their potential ecotoxicological impacts. The present study aims to characterize the levels of phthalate metabolites in muscle tissue of yellow eels (Anguilla anguilla) from two coastal Mediterranean lagoons, during three sampling periods. Nine phthalate metabolites were detected in >70% of the samples. Slightly higher levels of phthalate metabolites were detected in March and June compared to October, suggesting possible seasonal variations in environmental release and/or phthalate metabolization process by eels. The large sample size (N=117) made it possible to explore correlations between phthalate metabolites' levels and individual parameters, such as body length, age, body condition and hepatic histo-pathologies. Body length and estimated age poorly correlated with phthalate metabolites, suggesting that eels did not accumulate phthalates during growth, contrary to persistent compounds. Eels presented different grades of hepatic fibrosis and lipidosis. A negative correlation was found between the severity of these pathologies in the liver and the sum of phthalate metabolites levels, supporting the hypothesis that eels with damaged liver are less able to metabolize xenobiotics. PMID- 27412482 TI - Pre-discharge home visits by occupational therapists completed for patients following hip fracture. AB - BACKGROUND/AIM: Home visits by occupational therapists are a routine part of practice, but there remains little understanding about factors that are associated with the decision to complete a home visit. The aim of this study was to investigate the rate of pre-discharge home visits by occupational therapists for patients following hip fracture and explore factors associated with their occurrence. METHODS: A retrospective cohort study including 293 patients admitted to a metropolitan health service following hip fracture. Multi-variate logistic regression was used to identify significant variables associated with receiving a home visit. RESULTS: Home visits were conducted by occupational therapists for 28% of patients admitted from a private residence, and for less than 5% of patients admitted from low-level residential care facilities. The variables significantly associated with receiving a home visit at a private residence were older age and being admitted to a rehabilitation ward, but the model only explained between 9% and 13% of the variance. Other clinical and socio demographic variables evaluated were not associated with the provision of a home visit. CONCLUSIONS: About one in four people admitted to hospital from a private residence following hip fracture receive a home visit. The results suggest that whether or not a patient receives a home visit has little to do with socio demographic or clinical factors at the time of admission to hospital. There remains much unexplained variation in whether or not a patient receives a home visit and this study highlights the diversity that exists in clinical practice. PMID- 27412481 TI - Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation. AB - BACKGROUND: Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. RESULTS: We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture. CONCLUSIONS: Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum. PMID- 27412483 TI - Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells. AB - Currently, there is no viable treatment available for Parkinson's disease (PD) that stops or reverses disease progression. Interestingly, studies testing the glucagon-like-peptide-1 (GLP-1) mimetic Exendin-4 have shown neuroprotective/neurorestorative properties in pre-clinical tests and in a pilot clinical study of PD. Incretin analogues were originally developed to treat type 2 diabetes and several are currently on the market. In this study, we tested novel incretin analogues on the dopaminergic SH-SY5Y neuroblastoma cells against a toxic mitochondrial complex I inhibitor, Rotenone. Here, we investigate for the first time the effects of six different incretin receptor agonists - Liraglutide, D-Ser2-Oxyntomodulin, a GLP-1/GIP Dual receptor agonist, dAla(2)-GIP-GluPal, Val(8)GLP-1-GluPal and exendin-4. Post-treatment with doses of 1, 10 or 100 nM of incretin analogues for 12 h increased the survival of SH-SY5Y cells treated with 1 MUM Rotenone for 12 h. Furthermore, we studied the post-treatment effect of 100 nM incretin analogues against 1 MUM Rotenone stress on apoptosis, mitochondrial stress and autophagy markers. We found significant protective effects of the analogues against Rotenone stress on cell survival and on mitochondrial and autophagy-associated markers. The novel GLP-1/GIP Dual receptor agonist was superior and effective at a tenfold lower concentration compared to the other analogues. Using the Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, we further show that the neuroprotective effects are partially PI3K-independent. Our data suggest that the neuroprotective properties exhibited by incretin analogues against Rotenone stress involve enhanced autophagy, increased Akt-mediated cell survival and amelioration of mitochondrial dysfunction. These mechanisms can explain the neuroprotective effects of incretin analogues reported in clinical trials. GLP-1, GIP and dual incretin receptor agonists showed protective effects in SH-SY5Y cells treated with the stressor Rotenone. The novel GLP-1/GIP dual receptor agonist was superior and effective at a tenfold lower concentration compared to the other analogues. The drugs protected the cells from rotenone induced impairment in cell growth and Akt activation, mitochondrial damage, impairments of autophagy and apoptotic cell signalling. See paper for details. PMID- 27412484 TI - Nerve conduction velocity in CMT1A: what else can we tell? AB - BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A. METHODS: Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot-Marie-Tooth Examination Score (CMTES). RESULTS: NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES. CONCLUSIONS: This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length-dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients. PMID- 27412486 TI - WHICH AIRWAY PRESSURE SHOULD BE APPLIED DURING BREATH-HOLD IN DOGS UNDERGOING THORACIC COMPUTED TOMOGRAPHY? AB - This randomized controlled trial study aimed to identify the optimal positive pressure (PP) level that can clear atelectasis while avoiding pulmonary hyperinflation during the breath-hold technique in dogs undergoing thoracic computed tomography (CT). Sixty dogs affected by mammary tumors undergoing thoracic CT for the screening of pulmonary metastases were randomly assigned to six groups with different levels of PP during the breath-hold technique: 0 (control), 5 (PP5), 8 (PP8), 10 (PP10), 12 (PP12), and 15 (PP15) cmH2 O. The percentage of atelectatic lung region was lower in the PP10 (3.7 +/- 1.1%; P = 0.002), PP12 (3.4 +/- 1.3%; P = 0.0001), and PP15 (2.8 +/- 0.9%; P = 0.006) groups than in the control group (5.0 +/- 2.3%), and the percentage of poorly aerated lung region was lower in the PP8 (15.1 +/- 2.6%; P = 0.0009), PP10 (13.0 +/- 2.0 %; P = 0.002), PP12 (13.0 +/- 2.2 %; P = 0.0002), and PP15 (11.1 +/- 1.9%; P = 0.0002) groups than in the control group (19.8 +/- 5.0). The percentage of normally aerated lung region, however, was higher in the PP10 (79.7 +/- 4.1%; P = 0.005), PP12 (79.8 +/- 5.1%; P = 0.0002), and PP15 (80.2 +/- 4.9%; P = 0.002) groups than in the control group (73.4 +/- 6.6%). A PP of 10-12 cmH2 O during the breath-hold technique should be considered to improve lung aeration during a breath-hold technique in dogs undergoing thoracic CT. PMID- 27412487 TI - Electrochemistry at the Nanoscale. PMID- 27412485 TI - Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase. AB - The bladder urothelium is more than just a barrier. When the bladder is distended, the urothelium functions as a sensor to initiate the voiding reflex, during which it releases ATP via multiple mechanisms. However, the mechanisms underlying this ATP release in response to the various stretch stimuli caused by bladder filling remain largely unknown. Therefore, the aim of this study was to elucidate these mechanisms. By comparing vesicular nucleotide transporter (VNUT) deficient and wild-type male mice, we showed that ATP has a crucial role in urine storage through exocytosis via a VNUT-dependent mechanism. VNUT was abundantly expressed in the bladder urothelium, and when the urothelium was weakly stimulated (i.e. in the early filling stages), it released ATP by exocytosis. VNUT-deficient mice showed reduced bladder compliance from the early storage phase and displayed frequent urination in inappropriate places without a change in voiding function. We conclude that urothelial, VNUT-dependent ATP exocytosis is involved in urine storage mechanisms that promote the relaxation of the bladder during the early stages of filling. PMID- 27412488 TI - Regulating CAR T Cells: A Remote Control Approach. AB - Researchers have synthesized small organic molecules called adaptors that have a tumor-specific ligand on one end and FITC on the other. Instead of engineering a different chimeric antigen receptor (CAR) on T cells for each unique tumor antigen, these antigen-specific adaptors can be used to bridge FITC-binding CAR T and tumor cells. PMID- 27412489 TI - Deterministic distribution of four-photon Dicke state over an arbitrary collective-noise channel with cross-Kerr nonlinearity. AB - We present two deterministic quantum entanglement distribution protocols for a four-photon Dicke polarization entangled state resorting to the frequency and spatial degrees of freedom, which are immune to an arbitrary collective-noise channel. Both of the protocols adopt the X homodyne measurement based on the cross-Kerr nonlinearity to complete the task of the single-photon detection with nearly unit probability in principle. After the four receivers share the photons, they add some local unitary operations to obtain a standard four-photon Dicke polarization entangled state. PMID- 27412491 TI - The quest for rationalizing the magnetism in purely organic semiquinone-bridged bisdithiazolyl molecular magnets. AB - Semiquinone-bridged bisdithiazolyl-based radicals (XBBO) are appealing purely organic magnetic building blocks for the synthesis of new functional materials. Remarkably, for the phenyl-derivative PhBBO, the rationalization of its magnetism becomes a proof of concept that DFT can dramatically fail to evaluate JAB magnetic interactions between purely organic radical pairs. Instead, wavefunction based methods are required. Once JAB's are fully characterized, the magnetic topology of PhBBO is disclosed to consist of ferromagnetic FM pi-stacks that are very weakly coupled (by FM and AFM JAB interactions). The magnetic susceptibility chiT(T) and magnetization M(H) of PhBBO are then calculated using a first principles bottom-up approach. The study of the unit cell contraction upon cooling from room temperature to zero-Kelvin is relevant to propose a suitable model for the phase transition that occurs at 4.5 K. A simplistic picture tells us that the antiparallel-aligned 1D-FM-chains convert into domains of weakly either FM- or AFM-coupled 1D-FM-chains. Accordingly, the presence of these domains may introduce geometrical spin frustration below 4.5 K. PMID- 27412490 TI - Colored Indicator Undergloves Increase the Detection of Glove Perforations by Surgeons During Small Animal Orthopedic Surgery: A Randomized Controlled Trial. AB - OBJECTIVE: To determine whether use of colored indicator gloves affects perforation detection rate and to identify risk factors for glove perforation during veterinary orthopedic surgery. STUDY DESIGN: Prospective randomized controlled trial. SAMPLE POPULATION: 574 double pairs of gloves worn during 300 orthopedic surgical procedures (2,296 gloves). METHODS: Primary and assistant surgeons double-gloved for all orthopedic surgical procedures. Type of inner glove (standard or colored indicator) was randomized for the first 360 double pairs of gloves worn by surgeons during 180 procedures. Perforations detected by surgeons were recorded and gloves changed if requested. For a further 120 procedures, indicator gloves were used exclusively. All gloves were leak-tested after surgery to identify perforations. Association between potential risk factors and perforation was explored using multivariate logistical regression analysis. RESULTS: Glove perforations occurred during 43% of surgeries with a mean of 2.3 holes/surgery. Inner gloves were intact in 63% of glove pairs where an outer perforation occurred. Intraoperative perforation detection was improved when colored indicator gloves were worn (83% sensitivity) vs. standard gloves (34% sensitivity; P<.001). Independent risk factors for perforation were placement of plates and/or screws (P=.001; OR=2.4; 95% CI, 1.4-4.0), placement of an external skeletal fixator (P=.002; OR=7.0; 95% CI, 2.1-23.8), use of orthopedic wire (P=.011; OR=2.4; 95% CI, 1.2-4.7), and primary surgeon being board-certified (P=.016; OR=1.9; 95% CI, 1.1-3.1). CONCLUSION: Increased surgeon recognition of glove perforations through use of colored indicator gloves enables prompt change of gloves if perforation occurs and may reduce potential contamination of the surgical site. PMID- 27412492 TI - Neuroinflammation pathways: a general review. AB - Activated microglial cells play an important role in immune and inflammatory responses in central nervous system and neurodegenerative diseases. Many pro apoptotic pathways are mediated by signaling molecules that are produced during neuroinflammation. In glial cells, NF-kappaB, a transcription factor, initiates and regulates the expression of several inflammatory processes during inflammation which are attributed to the pathology of the several neurodegenerative diseases. In this review, we discuss the most important neuroinflammatory mediators with their pathways. Attenuating cytokines production and controlling microglial inflammatory response, which are the result of understanding neuroinflammation pathways, are considered therapeutic strategies for treating neurodegenerative diseases with an inflammatory component. PMID- 27412493 TI - Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature. AB - Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials. PMID- 27412494 TI - Electronic structure of CuTPP and CuTPP(F) complexes: a combined experimental and theoretical study II. AB - The unoccupied electronic structure of thick films of tetraphenylporphyrin and tetrakis(pentafluorophenyl)porphyrin Cu(ii) complexes (hereafter, CuTPP and CuTPP(F)) deposited on Au(111) has been studied by combining the outcomes of near edge X-ray absorption fine structure (NEXAFS) spectroscopy with those of spin unrestricted time-dependent density functional (TD-DFT) calculations carried out either within the scalar relativistic zeroth order regular approximation (ZORA) framework (C, N and F K-edges) or by using the Tamm-Dancoff approximation coupled to ZORA and including spin-orbit effects (Cu L2,3-edges). Similarly to the modelling of NEXAFS outcomes pertaining to other Cu(ii) complexes, the agreement between theory and experiment is more than satisfactory, thus confirming the open shell TD-DFT to be a useful tool to look into NEXAFS results pertinent to Cu(ii) compounds. The combined effect of metalation and phenyl (Ph) fluorine decoration is found to favour an extensive mixing between (Ph)sigma* and pristine porphyrin macrocyle (pmc) (pmc)pi* virtual levels. The lowest lying excitation in the C and N K-edge spectra of both CuTPP and CuTPP(F) is associated with a ligand-to-metal charge-transfer transition, unambiguously revealed in the (CuTPP)N K-edge spectral pattern. Moreover, the comparison with literature data pertaining to the modelling of the (Cu(II))L2,3 features in the phthalocyanine-Cu(ii) (CuPc) complex provided further insights into how metal-to-ligand-charge-transfer transitions associated with excitations from 2p(Cu(II)) AOs to low-lying, ligand based pi* MOs may contribute to the Cu(ii) L2,3-edge intensity and thus weaken its believed relationship with the Cu(ii)-ligand symmetry-restricted covalency. Despite the coordinative pocket of CuTPP/CuTPP(F) mirroring CuPc, the ligand field strength exerted by the phthalocyanine ligand on the Cu(ii) centre is experimentally found and theoretically confirmed to be slightly stronger than that experienced by Cu in CuTPP and CuTPP(F). On the whole, the obtained results complement those published in the near past by the same group on the occupied and empty states of the H2TPP and H2TPP(F) free ligands as well as on the occupied states of both CuTPP and CuTPP(F), thus providing the final piece to get a thorough description of electronic perturbations associated with the metalation and the Ph halogen decoration of H2TPP. PMID- 27412495 TI - Neonicotinoid-contaminated pollinator strips adjacent to cropland reduce honey bee nutritional status. AB - Worldwide pollinator declines are attributed to a number of factors, including pesticide exposures. Neonicotinoid insecticides specifically have been detected in surface waters, non-target vegetation, and bee products, but the risks posed by environmental exposures are still not well understood. Pollinator strips were tested for clothianidin contamination in plant tissues, and the risks to honey bees assessed. An enzyme-linked immunosorbent assay (ELISA) quantified clothianidin in leaf, nectar, honey, and bee bread at organic and seed-treated farms. Total glycogen, lipids, and protein from honey bee workers were quantified. The proportion of plants testing positive for clothianidin were the same between treatments. Leaf tissue and honey had similar concentrations of clothianidin between organic and seed-treated farms. Honey (mean+/-SE: 6.61 +/- 0.88 ppb clothianidin per hive) had seven times greater concentrations than nectar collected by bees (0.94 +/- 0.09 ppb). Bee bread collected from organic sites (25.8 +/- 3.0 ppb) had significantly less clothianidin than those at seed treated locations (41.6 +/- 2.9 ppb). Increasing concentrations of clothianidin in bee bread were correlated with decreased glycogen, lipid, and protein in workers. This study shows that small, isolated areas set aside for conservation do not provide spatial or temporal relief from neonicotinoid exposures in agricultural regions where their use is largely prophylactic. PMID- 27412496 TI - Dynamics of dental evolution in ornithopod dinosaurs. AB - Ornithopods were key herbivorous dinosaurs in Mesozoic terrestrial ecosystems, with a variety of tooth morphologies. Several clades, especially the 'duck billed' hadrosaurids, became hugely diverse and abundant almost worldwide. Yet their evolutionary dynamics have been disputed, particularly whether they diversified in response to events in plant evolution. Here we focus on their remarkable dietary adaptations, using tooth and jaw characters to examine changes in dental disparity and evolutionary rate. Ornithopods explored different areas of dental morphospace throughout their evolution, showing a long-term expansion. There were four major evolutionary rate increases, the first among basal iguanodontians in the Middle-Late Jurassic, and the three others among the Hadrosauridae, above and below the split of their two major clades, in the middle of the Late Cretaceous. These evolutionary bursts do not correspond to times of plant diversification, including the radiation of the flowering plants, and suggest that dental innovation rather than coevolution with major plant clades was a major driver in ornithopod evolution. PMID- 27412497 TI - Increased serum G72 protein levels in patients with schizophrenia: a potential candidate biomarker. AB - OBJECTIVE: The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study. Materials and methods In total, 107 patients with a diagnosis of schizophrenia according to the inclusion and exclusion criteria and 60 age-sex-matched healthy controls were included in the study. The groups were compared regarding serum G72 protein levels. RESULTS: The mean serum G72 protein values were 495.90+/-152.03 pg/ml in the schizophrenia group and 346.10+/-102.08 pg/ml in the healthy control group. The mean serum G72 protein level was significantly increased in the schizophrenia group compared with the healthy control group (t=-3.89, p<0.001). A receiver operating characteristics analysis was performed to compare the schizophrenia and healthy control groups. It was determined that the cut-off value was 141.51 pg/ml with a sensitivity of 0.991 and a specificity of 0.821. CONCLUSION: We suggest that serum G72 protein levels may represent a candidate biomarker for schizophrenia and have confirmed the results of the previous preliminary study. Additional studies with larger sample sizes and the inclusion of first episode schizophrenia patients are required to clarify the reliability and validity of serum G72 protein levels as a biomarker for schizophrenia. PMID- 27412499 TI - Metallosis After Swanson Spacer as Indication for Volar Synovectomy 12 Years After Implantation. AB - The treatment of metacarpophalangeal destruction by rheumatoid arthritis is an indication for arthroplasty, the swanson spacer is one of the options. The flexible silicone spacer may be implanted with or without titanium guide sleeves ("grommets"). However, the imaginary abrasion protection for the silicone grommets may in turn lead through micro-movements to wear. A 69 years old female patient suffering from rheumatoid arthritis for 30 years is presented. 12 years ago swansen spacers were implanted to metacarpo-phalangeal joints 2 -5 of the right hand. Due to pain, limited movement and swelling at the volar MCP joints she presented at our clinic. Volar synovectomy of the 3rd ray of the right hand was performed, the A2 ring band could be spared. There was massive metallosis induced by wear of the grommets in the third volar tendon sheath, the other flexors were free of metallosis. These results show that in synovitis after swanson spacer implantation using grommets the differential diagnosis of metallosis must be included and complete synovectomy is the treatment of choice. PMID- 27412498 TI - Biological characterization of bovine mammary epithelial cell lines immortalized by HPV16 E6/E7 and SV40T. AB - Primary bovine mammary epithelial cells are not ideal models for long-term studies, because primary cells undergo a limited number of proliferations in vitro and enter into a growth-arrest stage called cell replicative senescence; we therefore must establish the immortalized bovine mammary epithelial cells (BMECs) in vitro. More importantly, the mechanisms of the relationship between immortalized and apoptotic cell remain unknown in BMECs. We therefore sought to elucidate the mechanisms of which immortalized cells escape the pathway of apoptotic signal. These cells were successfully immortalized without any signs of senescence. The maximum number of BMEC and E6E7 immortalized cells were reached after 6 d of culture. At this point, there were significantly more E6E7 immortalized cells than primary BMECs (P < 0.01). The population-doubling times of the E6E7 and SV40T immortalized cells were lowest at 48 and 72 h. We failed to detect the expression of the epithelial cell marker E-cadherin in BMECs; however, immortalized cells had low expression of E-cadherin. The expression of beta catenin was markedly expressed in immortalized cells than in BMECs (P < 0.01). Caspase-3, caspase-9, and poly ADP-ribose polymerase (PARP) were detected; however, the cleavage of caspase-3 and PARP was not observed. Our data demonstrate that the expressions of caspase-9, caspase-3, and PARP are not sufficient for the apoptosis of immortalized cells and suggest that E-cadherin and beta-catenin might be an important indicator of the development of cancer. PMID- 27412500 TI - Rare Variants in the ADAMTS13 Von Willebrand Factor-Binding Domain Contribute to Pediatric Stroke. AB - BACKGROUND: Recently, we reported a gene network of ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) genes as central component of the genetic risk contributing to pediatric stroke. ADAMTS13 is a prime example for such a key component as it cleaves von Willebrand factor multimers, reduces platelet adhesion and aggregation, and downregulates thrombus formation and inflammation. METHODS AND RESULTS: We characterized the genetic architecture of ADAMTS13 through targeted next-generation sequencing of 48 affected children and their unaffected siblings and identified in total 241 variants (single nucleotide polymorphisms or insertions/deletions) in the ADAMTS13 gene. From these, based on significance in the sibship disequilibrium test (P<0.05) or protein-altering properties, we selected 21 common variants covering the complete ADAMTS13 gene for genotyping in 270 trios and subsequent association analyses. Transmission disequilibrium testing was performed for affection status and ADAMTS13 activity levels using PLINK and FBAT, respectively. Ten single nucleotide polymorphisms were significantly associated with pediatric stroke (P<0.05 to P<0.001), 2 of which (rs2285489 and rs28793911) were also significantly associated with ADAMTS13 levels (P=0.0004 and P=0.0092). The resulting protective haplotype H1.1. (T:U 95.5: 144.4; P=0.0016) is associated with increased ADAMTS13 levels (age-adjusted P=0.0108). Haplotype association using a sliding window approach assigns this association to the ADAMTS13 von Willebrand factor-binding domain (P=1.2*10(-4)). CONCLUSIONS: Our data provide a link between the genetic architecture of ADAMTS13, ADAMTS13 levels, and stroke susceptibility. Altogether, these studies render ADAMTS13 an attractive candidate for functional studies and may contribute to personalized diagnosis and treatment options in future. PMID- 27412501 TI - Pediatric thyroid FNA biopsy: Outcomes and impact on management over 24 years at a tertiary care center. AB - BACKGROUND: Thyroid malignancy is rare in young children, although the incidence increases sharply during adolescence. Nodular thyroid disease and thyroid cancer in children differ substantially from those in adults, because the rates of malignancy among children are roughly 5-fold higher, and local and distant metastases as well as recurrences are more common. Even with the recent introduction of pediatric guidelines, there remains a paucity of pediatric data on which to base clinical decision making. The objectives of this study were to characterize the outcomes of fine-needle aspiration biopsy (FNAB) of nodular thyroid disease at a pediatric tertiary-care institution over a 24-year period and to relate cytopathology to histopathology and management decisions in this population. METHODS: A retrospective review of patients who underwent preoperative FNAB and thyroid surgery between 1992 and 2015 was conducted. In total, 207 nodules were biopsied among 178 patients. RESULTS: Adequate FNAB samples were obtained in 74% of biopsies. Sixty-five patients underwent thyroidectomy after FNAB. In this group, the malignancy rates for lesions deemed benign, atypical, suspicious, and malignant on FNAB cytology were 16%, 67%, 71%, and 100%, respectively. Twenty-seven individuals underwent >1 biopsy; however, no malignancies were identified in these patients. Surprisingly, the rate of malignancy in patients who underwent preoperative FNAB was not significantly different from the rate in those who proceeded directly to surgery (n = 146). CONCLUSIONS: FNAB remains a valuable tool for preoperative assessment of pediatric thyroid nodules. When samples are adequate for assessment, cytology other than clearly "benign" merits referral for diagnostic or therapeutic thyroidectomy. In this series, FNAB did not reduce rates of surgery for benign disease. Cancer Cytopathol 2016;124:801-10. (c) 2016 American Cancer Society. PMID- 27412502 TI - Short message service as an alternative in the drug consumption evaluation of persons with tuberculosis in Malang, Indonesia. AB - AIM: Short message service (SMS) is an applied technology of communication that enables the transfer of information and can be used as a part of medical efforts to motivate clients to improve their behavior regarding drug consumption. This study attempts to observe the differences in patients' behavior as a result of either using SMS to motivate their drug consumption or by using only health providers and outreach workers to monitor them. METHODS: This study used a post test-only controlled-group design with a simple random sampling technique and was held in Malang, Indonesia. The sample in this study consisted of 45 patients with tuberculosis (TB) who received motivating SMS messages and 45 patients with only health providers and outreach workers to monitor them. RESULTS: Fisher's Exact test using a 95% confidence interval showed that the result of this study had a P value of 0.059, which means that there was no difference in compliance with drug consumption between the patients who received SMS messages and the patients who were under the supervision of health providers and outreach workers. CONCLUSION: It is highly recommended that the application of SMS be included in TB treatment and the evaluation of patients as an alternative method of controlling patients' compliance with consuming anti-TB drugs at home. PMID- 27412503 TI - Chryseobacterium montanum sp. nov. isolated from mountain soil. AB - A Gram-staining-negative, strictly aerobic, non-spore-forming, rod-shaped bacterium, designated WG4T, was isolated from soil of the Tianmen Mountain located in Hunan province, PR China. 16S rRNA gene sequence analysis showed that the strain belongs to the genus Chryseobacterium in the family Flavobacteriaceae, with 97.4 % and 97.1 % sequence identities to Chryseobacterium anthropi NF 1366T and Chryseobacterium haifense H38T, respectively. In comparison with the other strains representing the genus Chryseobacterium, the 16S rRNA gene sequence identities were less than 97.0 %. The DNA-DNA relatedness values were 63.3 % (+/ 1) between C. anthropi NF 1366T and strain WG4T and 62.7 % (+/-2) between C. haifense DSM 19056T and strain WG4T. The DNA G+C content of strain WG4T was 37.7 mol%. The predominant fatty acids of strain WG4T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, three unidentified lipids and two unidentified aminolipids. The major menaquinone of strain WG4T was menaquinone 6. Strain WG4T showed some unique physiological and biochemical characteristics, such as being negative for gelatin hydrolysis, and valine arylamidase and alpha-glucosidase activity, and positive for acid production from cellobiose. Based on the differentiating phylogenetic inference and biochemical data, strain WG4T represents a novel species, for which the name Chryseobacterium montanum sp. nov. is proposed, with the type strain WG4T (=KCTC 52204T=CCTCC AB 2016058T). PMID- 27412504 TI - B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity. AB - B lymphocytes contribute to the pathogenesis of Multiple Sclerosis (MS) by secreting antibodies and producing cytokines. This latter function was analyzed in myelin olygodendrocyte protein (MOG)-stimulated CD19+ B lymphocytes of 71 MS patients with different disease phenotypes and 40 age-and sex-matched healthy controls (HC). Results showed that: 1) CD19+/TNFalpha+, CD19+/IL-12+ and CD19+/IFNgamma+ lymphocytes are significantly increased in primary progressive (PP) compared to secondary progressive (SP), relapsing-remitting (RR), benign (BE) MS and HC; 2) CD19+/IL-6+ lymphocytes are significantly increased in PP, SP and RR compared to BEMS and HC; and 3) CD19+/IL-13+, CD19+/IL-10+, and CD19+/IL 10+/TGFbeta+ (Bregs) B lymphocytes are reduced overall in MS patients compared to HC. B cells expressing BTLA, a receptor whose binding to HVEM inhibits TcR initiated cytokine production, as well as CD19+/BTLA+/IL-10+ cells were also significantly overall reduced in MS patients compared to HC. Analyses performed in RRMS showed that fingolimod-induced disease remission is associated with a significant increase in Bregs, CD19+/BTLA+, and CD19+/BTLA+/IL-10+ B lymphocytes. B lymphocytes participate to the pathogenesis of MS via the secretion of functionally-diverse cytokines that might play a role in determining disease phenotypes. The impairment of Bregs and CD19+/BTLA+ cells, in particular, could play an important pathogenic role in MS. PMID- 27412506 TI - High throughput LSPR and SERS analysis of aminoglycoside antibiotics. AB - Aminoglycoside antibiotics are used in the treatment of infections caused by Gram negative bacteria, and are often dispensed only in severe cases due to their adverse side effects. Patients undergoing treatment with these antibiotics are therefore commonly subjected to therapeutic drug monitoring (TDM) to ensure a safe and effective personalised dosage. The ability to detect these antibiotics in a rapid and sensitive manner in human fluids is therefore of the utmost importance in order to provide effective monitoring of these drugs, which could potentially allow for a more widespread use of this class of antibiotics. Herein, we report on the detection of various aminoglycosides, by exploiting their ability to aggregate gold nanoparticles. The number and position of the amino groups of aminoglycoside antibiotics controlled the aggregation process. We investigated the complementary techniques of surface enhanced Raman spectroscopy (SERS) and localized surface plasmon resonance (LSPR) for dual detection of these aminoglycoside antibiotics and performed an in-depth study of the feasibility of carrying out TDM of tobramycin using a platform amenable to high throughput analysis. Herein, we also demonstrate dual detection of tobramycin using both LSPR and SERS in a single platform and within the clinically relevant concentration range needed for TDM of this particular aminoglycoside. Additionally we provide evidence that tobramycin can be detected in spiked human serum using only functionalised nanoparticles and SERS analysis. PMID- 27412507 TI - Dielectric-Backed Aperture Resonators for X-Band in vivo EPR Nail Dosimetry. AB - A new resonator for X-band in vivo EPR nail dosimetry, the dielectric-backed aperture resonator (DAR), is developed based on rectangular TE102 geometry. This novel geometry for surface spectroscopy improves at least a factor of 20 compared to a traditional non-backed aperture resonator. Such an increase in EPR sensitivity is achieved by using a non-resonant dielectric slab, placed on the aperture inside the cavity. The dielectric slab provides an increased magnetic field at the aperture and sample, while minimizing sensitive aperture resonance conditions. This work also introduces a DAR semi-spherical (SS)-TE011 geometry. The SS-TE011 geometry is attractive due to having twice the incident magnetic field at the aperture for a fixed input power. It has been shown that DAR provides sufficient sensitivity to make biologically relevant measurements both in vitro and in vivo Although in vivo tests have shown some effects of physiological motions that suggest the necessity of a more robust finger holder, equivalent dosimetry sensitivity of approximately 1.4 Gy has been demonstrated. PMID- 27412505 TI - Regulators of Cholangiocyte Proliferation. AB - Cholangiocytes, a small population of cells within the normal liver, have been the focus of a significant amount of research over the past two decades because of their involvement in cholangiopathies such as primary sclerosing cholangitis and primary biliary cholangitis. This article summarizes landmark studies in the field of cholangiocyte physiology and aims to provide an updated review of biliary pathogenesis. The historical approach of rodent extrahepatic bile duct ligation and the relatively recent utilization of transgenic mice have led to significant discoveries in cholangiocyte pathophysiology. Cholangiocyte physiology is a complex system based on heterogeneity within the biliary tree and a number of signaling pathways that serve to regulate bile composition. Studies have expanded the list of neuropeptides, neurotransmitters, and hormones that have been shown to be key regulators of proliferation and biliary damage. The peptide histamine and hormones, such as melatonin and angiotensin, angiotensin, as well as numerous sex hormones, have been implicated in cholangiocyte proliferation during cholestasis. Numerous pathways promote cholangiocyte proliferation during cholestasis, and there is growing evidence to suggest that cholangiocyte proliferation may promote hepatic fibrosis. These pathways may represent significant therapeutic potential for a subset of cholestatic liver diseases that currently lack effective therapies. PMID- 27412508 TI - Emergency EPR and OSL dosimetry with table vitamins and minerals. AB - Several table vitamins, minerals and L-lysine amino acid have been preliminarily tested as potential emergency dosemeters using electron paramagnetic resonance (EPR) and optically stimulated luminescence (OSL) techniques. Radiation-induced EPR signals were detected in samples of vitamin B2 and L-lysine while samples of multivitamins of different brands as well as mineral Mg demonstrated prominent OSL signals after exposure to ionizing radiation doses. Basic dosimetric properties of the radiation-sensitive substances were studied, namely dose response, fading of the EPR or OSL signals and values of minimum measurable doses (MMDs). For EPR-sensitive samples, the EPR signal is converted into units of dose using a linear dose response and correcting for fading using the measured fading dependence. For OSL-sensitive materials, a multi-aliquot, enhanced-temperature protocol was developed to avoid the problem of sample sensitization and to minimize the influence of signal fading. The sample dose in this case is also evaluated using the dose response and fading curves. MMDs of the EPR-sensitive samples were below 2 Gy while those of the OSL-sensitive materials were below 500 mGy as long as the samples are analyzed within 1 week after exposure. PMID- 27412509 TI - A New Cytogenetic Biodosimetry Image Repository for the Dicentric Assay. AB - The BioDoseNet was founded by the World Health Organization as a global network of biodosimetry laboratories for building biodosimetry laboratory capacities in countries. The newly established BioDoseNet image repository is a databank of ~25 000 electronically captured images of metaphases from the dicentric assay, which have been previously analysed by international experts. The detailed scoring results and dose estimations have, in most cases, already been published. The compilation of these images into one image repository provides a valuable tool for training and research purposes in biological dosimetry. No special software is needed to view and score the image galleries. For those new to the dicentric assay, the BioDoseNet Image Repository provides an introduction to and training for the dicentric assay. It is an excellent instrument for intra-laboratory training purposes or inter-comparisons between laboratories, as recommended by the International Organization for Standardisation standards. In the event of a radiation accident, the repository can also increase the surge capacity and reduce the turnaround time for dose estimations. Finally, it provides a mechanism for the discussion of scoring discrepancies in difficult cases. PMID- 27412511 TI - LONG-TERM BIODOSIMETRY REDUX. AB - This paper revisits and reiterates the needs, purposes and requirements of biodosimetric assays for long-term dose and health risk assessments. While the most crucial need for biodosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure assessment. Hence, the needs for retrospective dose estimation are likely to be greater in the future. The value of biodosimetry can be considerably enhanced with the development of new or improved methods, particularly with suitability for application at long periods of time after exposure. PMID- 27412510 TI - THE DECADE OF THE RABiT (2005-15). AB - The RABiT (Rapid Automated Biodosimetry Tool) is a dedicated Robotic platform for the automation of cytogenetics-based biodosimetry assays. The RABiT was developed to fulfill the critical requirement for triage following a mass radiological or nuclear event. Starting from well-characterized and accepted assays we developed a custom robotic platform to automate them. We present here a brief historical overview of the RABiT program at Columbia University from its inception in 2005 until the RABiT was dismantled at the end of 2015. The main focus of this paper is to demonstrate how the biological assays drove development of the custom robotic systems and in turn new advances in commercial robotic platforms inspired small modifications in the assays to allow replacing customized robotics with 'off the shelf' systems. Currently, a second-generation, RABiT II, system at Columbia University, consisting of a PerkinElmer cell::explorer, was programmed to perform the RABiT assays and is undergoing testing and optimization studies. PMID- 27412512 TI - THE EFFECT OF BACKGROUND SIGNAL AND ITS REPRESENTATION IN DECONVOLUTION OF EPR SPECTRA ON ACCURACY OF EPR DOSIMETRY IN BONE. AB - This study is about the accuracy of EPR dosimetry in bones based on deconvolution of the experimental spectra into the background (BG) and the radiation-induced signal (RIS) components. The model RIS's were represented by EPR spectra from irradiated enamel or bone powder; the model BG signals by EPR spectra of unirradiated bone samples or by simulated spectra. Samples of compact and trabecular bones were irradiated in the 30-270 Gy range and the intensities of their RIS's were calculated using various combinations of those benchmark spectra. The relationships between the dose and the RIS were linear (R2 > 0.995), with practically no difference between results obtained when using signals from irradiated enamel or bone as the model RIS. Use of different experimental spectra for the model BG resulted in variations in intercepts of the dose-RIS calibration lines, leading to systematic errors in reconstructed doses, in particular for high- BG samples of trabecular bone. These errors were reduced when simulated spectra instead of the experimental ones were used as the benchmark BG signal in the applied deconvolution procedures. PMID- 27412513 TI - ROC Analysis for Evaluation of Radiation Biodosimetry Technologies. AB - Receiver operating characteristic (ROC) analysis is a fundamental tool used for the evaluation and comparison of diagnostic systems that provides estimates of the combinations of sensitivity and specificity that can be achieved with a given technique. Along with critical considerations of practical limitations, such as throughput and time to availability of results, ROC analyses can be applied to provide meaningful assessments and comparisons of available biodosimetry methods. Accordingly, guidance from the Food and Drug Administration to evaluate biodosimetry devices recommends using ROC analysis. However, the existing literature for the numerous biodosimetry methods that have been developed to address the needs for triage either do not contain ROC analyses or present ROC analyses where the dose distributions of the study samples are not representative of the populations to be screened. The use of non-representative sample populations can result in a significant spectrum bias, where estimated performance metrics do not accurately characterize the true performance under real-world conditions. Particularly, in scenarios where a large group of people is screened because they were potentially exposed in a large-scale radiation event, directly measured population data do not exist. However, a number of complex simulations have been performed and reported in the literature that provide estimates of the required dose distributions. Based on these simulations and reported data about the output and uncertainties of biodosimetry assays, we illustrate how ROC curves can be generated that incorporate a realistic representative sample. A technique to generate ROC curves for biodosimetry data is presented along with representative ROC curves, summary statistics and discussion based on published data for triage-ready electron paramagnetic resonance in vivo tooth dosimetry, the dicentric chromosome assay and quantitative polymerase chain reaction assay. We argue that this methodology should be adopted generally to evaluate the performance of radiation biodosimetry screening assays so that they can be compared in the context of their intended use. PMID- 27412514 TI - Radiation Dose Estimation by Automated Cytogenetic Biodosimetry. AB - The dose from ionizing radiation exposure can be interpolated from a calibration curve fit to the frequency of dicentric chromosomes (DCs) at multiple doses. As DC counts are manually determined, there is an acute need for accurate, fully automated biodosimetry calibration curve generation and analysis of exposed samples. Software, the Automated Dicentric Chromosome Identifier (ADCI), is presented which detects and discriminates DCs from monocentric chromosomes, computes biodosimetry calibration curves and estimates radiation dose. Images of metaphase cells from samples, exposed at 1.4-3.4 Gy, that had been manually scored by two reference laboratories were reanalyzed with ADCI. This resulted in estimated exposures within 0.4-1.1 Gy of the physical dose. Therefore, ADCI can determine radiation dose with accuracies comparable to standard triage biodosimetry. Calibration curves were generated from metaphase images in ~10 h, and dose estimations required ~0.8 h per 500 image sample. Running multiple instances of ADCI may be an effective response to a mass casualty radiation event. PMID- 27412515 TI - Anomalous changes in atmospheric radon concentration before and after the 2011 northern Wakayama Earthquake (Mj 5.5). AB - A significant increase in atmospheric radon concentration was observed in the area around the epicentre before and after the occurrence of the shallow inland earthquake in the northern Wakayama Prefecture on 5 July 2011 (Mj 5.5, depth 7 km) in Japan. The seismic activity in the sampling site was evaluated to identify that this earthquake was the largest near the sampling site during the observation period. To determine whether this was an anomalous change, the atmospheric daily minimum radon concentration measured for a 13-year period was analysed. When the residual radon concentration values without the seasonal radon variation and the linear trend was > 3 standard deviations of the residual radon variation corresponding to the normal period, the values were deemed as anomalous. As a result, an anomalous increase in radon concentration was determined before and after the earthquake. In conclusion, anomalous change related to earthquakes with at least Mj 5.5 can be detected by monitoring atmospheric radon near the epicentre. PMID- 27412516 TI - Determination of the Average Native Background and the Light-Induced EPR Signals and their Variation in the Teeth Enamel Based on Large-Scale Survey of the Population. AB - The aim of the study is to determine the average intensity and variation of the native background signal amplitude (NSA) and of the solar light-induced signal amplitude (LSA) in electron paramagnetic resonance (EPR) spectra of tooth enamel for different kinds of teeth and different groups of people. These values are necessary for determination of the intensity of the radiation-induced signal amplitude (RSA) by subtraction of the expected NSA and LSA from the total signal amplitude measured in L-band for in vivo EPR dosimetry. Variation of these signals should be taken into account when estimating the uncertainty of the estimated RSA. A new analysis of several hundred EPR spectra that were measured earlier at X-band in a large-scale examination of the population of the Central Russia was performed. Based on this analysis, the average values and the variation (standard deviation, SD) of the amplitude of the NSA for the teeth from different positions, as well as LSA in outer enamel of the front teeth for different population groups, were determined. To convert data acquired at X-band to values corresponding to the conditions of measurement at L-band, the experimental dependencies of the intensities of the RSA, LSA and NSA on the m.w. power, measured at both X and L-band, were analysed. For the two central upper incisors, which are mainly used in in vivo dosimetry, the mean LSA annual rate induced only in the outer side enamel and its variation were obtained as 10 +/- 2 (SD = 8) mGy y-1, the same for X- and L-bands (results are presented as the mean +/- error of mean). Mean NSA in enamel and its variation for the upper incisors was calculated at 2.0 +/- 0.2 (SD = 0.5) Gy, relative to the calibrated RSA dose response to gamma radiation measured under non-power saturation conditions at X band. Assuming the same value for L-band under non-power saturating conditions, then for in vivo measurements at L-band at 25 mW (power saturation conditions), a mean NSA and its variation correspond to 4.0 +/- 0.4 (SD = 1.0) Gy. PMID- 27412517 TI - Chronic intermittent hypoxia induces cardiac hypertrophy by impairing autophagy through the adenosine 5'-monophosphate-activated protein kinase pathway. AB - Autophagy is tightly regulated to maintain cardiac homeostasis. Impaired autophagy is closely associated with pathological cardiac hypertrophy. However, the relationship between autophagy and cardiac hypertrophy induced by chronic intermittent hypoxia (CIH) is not known. In the present study, we measured autophagy-related genes and autophagosomes during 10 weeks of CIH in rats, and 6 days in H9C2 cardiomyocytes, and showed that autophagy was impaired. This conclusion was confirmed by the autophagy flux assay. We detected significant hypertrophic changes in myocardium with impaired autophagy. Rapamycin, an autophagy enhancer, attenuated the cardiac hypertrophy induced by CIH. Moreover, silencing autophagy-related gene 5 (ATG5) exerted the opposite effect. The role of adenosine monophosphate-activated protein kinase (AMPK) in regulating autophagy under CIH was confirmed using AICAR to upregulate this enzyme and restore autophagy flux. Restoring autophagy by AICAR or rapamycin significantly reversed the hypertrophic changes in cardiomyocytes. To investigate the mechanism of autophagy impairment, we compared phospho (p)-AMPK, p-Akt, cathepsin D, and NFAT3 levels, along with calcineurin activity, between sham and CIH groups. CIH activated calcineurin, and inhibited AMPK and AMPK-mediated autophagy in an Akt- and NFAT3-independent manner. Collectively, these data demonstrated that impaired autophagy induced by CIH through the AMPK pathway contributed to cardiac hypertrophy. PMID- 27412518 TI - Hermaphroditism in a Roman fresco from Herculaneum (first century A.D.), National Archaeological Museum, Naples, Italy. PMID- 27412519 TI - Simultaneous determination of notoginsenoside R1 and ginsenoside Re in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study. AB - A rapid and high sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of notoginsenoside R1 and ginsenoside Re in rat plasma was developed. The analytes and internal standard, digoxin, were extracted from rat plasma via protein precipitation with methanol and separated on an Phenomenex Gemini C18 column within 2 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive ion mode. The precursor to product ion transitions monitored for notoginsenoside R1, ginsenoside Re, and internal standard were m/z 955.5->775.5, 969.6->789.1, and 803.6->283.1, respectively. The assay was validated with linear range of 1.9-380 ng/mL for notoginsenoside R1 and 0.5-100 ng/mL for ginsenoside Re. The intra- and interday precisions (RSD%) were within 8.96% for each analyte. The absolute recoveries were greater than 93% for R1 and 96% for Re. Each analyte was stable during all sample storage, preparation, and analytic procedures. The method was successfully applied to a pharmacokinetic study of Xuesaitong dispersible tablets in eight rats. PMID- 27412520 TI - Oral health-related quality of life and esthetic outcome in single anterior maxillary implants. AB - OBJECTIVES: The aim of this study is twofold: to assess the esthetic outcome of single dental implant restorations in the anterior maxillary area after up to 3 years of function, and to evaluate the relationship between the esthetic outcome and oral health-related quality of life. MATERIALS AND METHODS: Twenty patients who were treated with an anterior maxillary single implant restoration were recalled for esthetic outcome evaluation using pink and white esthetic scores (PES/WES). All patients completed a questionnaire regarding satisfaction of treatment outcome and quality of life related to the implant restorations. Patient satisfaction was assessed by visual analog scales (VAS) analysis, whereas oral impact on daily life performances (OIDP) was used to evaluate the quality of life of patients. RESULTS: The esthetic outcome assessed by PES/WES showed favorable results. The median PES/WES scores were 16.00 (maximum possible score = 20). The median PES scores and WES scores were 7.50 and 8.00, respectively. Patient satisfaction rated in VAS scale ranged from 8 to 10. OIDP assessment showed an impact on daily life performance in 45% of patients. The most common impacts were eating (n = 5) and cleaning teeth (n = 4). No significant difference in PES/WES scores was found between the patients who perceived and did not perceive oral impacts. CONCLUSIONS: There was some discrepancy between the dentist's evaluation and patient's perception but a strong positive satisfaction was reported from all patients which let suppose that the psychosocial factors that involve patient's perspective should be further investigated. PMID- 27412521 TI - Pharmacokinetics of ranitidine in preterm and term neonates with gastroesophageal reflux. AB - BACKGROUND: The aim of this study was to determine the effect of gestational age on pharmacokinetics of ranitidine in newborns with gastroesophageal reflux. METHODS: A prospective, descriptive and pharmacokinetic study was carried out in 30 pre-term and 20 full-term babies. 3 mg/kg of ranitidine was administered intravenously to all the babies and at 0.25, 0.5, 1, 2, 4, and 8 h following the administration, samples of blood were drawn to assess ranitidine levels using high performance liquid chromatographic technique. RESULTS: Pharmacokinetics of ranitidine had a bi-exponential behavior with a half-life elimination of (t1/2el) 2.79 h, area under curve (AUC) of 1688 ng/mL, volume of distribution (Vd) of 1.44 L/kg, and clearance (Cl) of 5.9 L/kg/h. The median plasmatic concentration in pre terms was 1113 ng/mL and 280 ng/mL in full-terms. Vd, t1/2 and Cl presented high values in preterm although the correlation of Cl with glomerular filtration in term newborns was better. CONCLUSIONS: Plasma levels of ranitidine depend on the gestational age of the newborns. However, the possible relationship between after birth age and pharmacokinetics of the neonates as their internal organs get matured without minding their gestational background. PMID- 27412522 TI - A review of empirical research related to the use of small quantitative samples in clinical outcome scale development. AB - INTRODUCTION: There has been a notable increase in the advocacy of using small sample designs as an initial quantitative assessment of item and scale performance during the scale development process. This is particularly true in the development of clinical outcome assessments (COAs), where Rasch analysis has been advanced as an appropriate statistical tool for evaluating the developing COAs using a small sample. METHODS: We review the benefits such methods are purported to offer from both a practical and statistical standpoint and detail several problematic areas, including both practical and statistical theory concerns, with respect to the use of quantitative methods, including Rasch consistent methods, with small samples. CONCLUSIONS: The feasibility of obtaining accurate information and the potential negative impacts of misusing large-sample statistical methods with small samples during COA development are discussed. PMID- 27412524 TI - Bone marrow contribution to synovial hyperplasia following joint surface injury. AB - BACKGROUND: Joint surface injury, a known risk factor for osteoarthritis, triggers synovial hyperplasia, which involves proliferation of mesenchymal stromal/stem cells (MSCs). Whether these proliferative MSCs are resident synovial cells or move into the tissue from elsewhere is not known. The aim of this study was to determine the contribution of bone marrow-derived cells to synovial hyperplasia following joint surface injury. METHODS: Lethally irradiated mice were transplanted with green fluorescent protein (GFP)-labelled bone marrow, and MSC chimerism was determined by the colony-forming unit fibroblast (CFU-F) assay and phenotypic analysis. To label host slow-cycling cells prior to bone marrow transplant, mice received iododeoxyuridine for 3 weeks. Mice then were subjected to GFP(+) bone marrow transplant, underwent joint surface injury and received chlorodeoxyuridine (CldU) for 7 days to label cells proliferating after injury. GFP- and nucleoside-labelled cells in normal and injured knee joint synovium were quantified in situ by immunofluorescence staining of paraffin-embedded tissue sections. The phenotype of GFP-labelled cells was determined by co-staining for the haematopoietic marker CD16/CD32 and the MSC/fibroblast marker platelet derived growth factor receptor alpha (Pdgfralpha). RESULTS: CFU-F assay and phenotypic analysis demonstrated successful bone marrow mesenchymal lineage chimerism in mice that underwent transplants. Bone marrow reconstitution preceded the detection of GFP-labelled cells in synovium. The percentage of GFP(+) cells in synovium increased significantly in response to injury, while the proportion of GFP(+) cells that were labelled with the proliferation marker CldU did not increase, suggesting that the expansion of the GFP(+) cell population in synovium was due mainly to bone marrow cell infiltration. In contrast, proliferation of host slow-cycling cells was significantly increased in the hyperplastic synovium. In both control and injured knee joints, the majority of marrow-derived GFP(+) cells in the synovium were haematopoietic (CD16/32(+)), while a minority of cells expressed the pan-fibroblast/MSC marker Pdgfralpha. CONCLUSIONS: Our findings indicate that synovial hyperplasia following joint surface injury involves proliferation of resident slow-cycling cells, with a contribution from infiltrating bone marrow-derived cells. Understanding the process of synovial hyperplasia may reveal ways to restore homeostasis in injured joints and prevent secondary osteoarthritis. PMID- 27412523 TI - Relating proton pumps with gap junctions: colocalization of ductin, the channel forming subunit c of V-ATPase, with subunit a and with innexins 2 and 3 during Drosophila oogenesis. AB - BACKGROUND: Ion-transport mechanisms and gap junctions are known to cooperate in creating bioelectric phenomena, like pH gradients, voltage gradients and ion fluxes within single cells, tissues, organs, and whole organisms. Such phenomena have been shown to play regulatory roles in a variety of developmental and regenerative processes. Using Drosophila oogenesis as a model system, we aim at characterizing in detail the mechanisms underlying bioelectric phenomena in order to reveal their regulatory functions. We, therefore, investigated the stage specific distribution patterns of V-ATPase components in relation to gap-junction proteins. RESULTS: We analysed the localization of the V-ATPase components ductin (subunit c) and subunit a, and the gap-junction components innexins 2 and 3, especially in polar cells, border cells, stalk cells and centripetally migrating cells. These types of follicle cells had previously been shown to exhibit characteristic patterns of membrane channels as well as membrane potential and intracellular pH. Stage-specifically, ductin and subunit a were found either colocalized or separately enriched in different regions of soma and germ-line cells. While ductin was often more prominent in plasma membranes, subunit a was more prominent in cytoplasmic and nuclear vesicles. Particularly, ductin was enriched in polar cells, stalk cells, and nurse-cell membranes, whereas subunit a was enriched in the cytoplasm of border cells, columnar follicle cells and germ line cells. Comparably, ductin and both innexins 2 and 3 were either colocalized or separately enriched in different cellular regions. While ductin often showed a continuous membrane distribution, the distribution of both innexins was mostly punctate. Particularly, ductin was enriched in polar cells and stalk cells, whereas innexin 2 was enriched in the oolemma, and innexin 3 in centripetally migrating follicle cells. In lateral follicle-cell membranes, the three proteins were found colocalized as well as separately concentrated in presumed gap junction plaques. CONCLUSIONS: Our results support the notion of a large variety of gap junctions existing in the Drosophila ovary. Moreover, since ductin is the channel-forming part of a proton pump and, like the innexins, is able to form junctional as well as non-junctional membrane channels, a plethora of cellular functions could be realized by using these proteins. The distribution and activity patterns of such membrane channels are expected to contribute to developmentally important bioelectric signals. PMID- 27412527 TI - Testing if Social Services Prevent Fatal Child Maltreatment Among a Sample of Children Previously Known to Child Protective Services. AB - The purpose of this article was to examine the potential impact of child welfare services on the risk for fatal child maltreatment. This was conducted using a subsample of children who were identified as "prior victims" in the National Child Abuse and Neglect Data System from 2008 to 2012. At the multivariate level, the analyses show that case management services act to protect children from death as do family support services, family preservation services, and foster care, but that the results vary by type of maltreatment experienced. The author recommends that before strong conclusions are drawn, additional research in this area is warranted. PMID- 27412525 TI - Travelers' health problems and behavior: prospective study with post-travel follow-up. AB - BACKGROUND: The annual number of international tourist arrivals has recently exceeded one billion, yet surprisingly few studies have characterized travelers' behavior, illness, and risk factors in a prospective setting. Particularly scarce are surveys of data spanning travel, return, and follow-up of the same cohort. This study examines behavior and illness among travelers while abroad, after return home, and at follow-up. Patterns of behavior connected to type of travel and illness are characterized so as to identify risk factors and provide background data for pre-travel advice. METHODS: Volunteers to this prospective cohort study were recruited at visits to a travel clinic prior to departure. Data on the subjects' health and behavior were collected by questionnaires before and after journeys and over a three-week follow-up. In addition, the subjects were asked to fill in health diaries while traveling. RESULTS: The final study population consisted of 460 subjects, 79 % of whom reported illness during travel or on arrival: 69 % had travelers' diarrhea (TD), 17 % skin problems, 17 % fever, 12 % vomiting, 8 % respiratory tract infection, 4 % urinary tract infection, 2 % ear infection, 4 % gastrointestinal complaints other than TD or vomiting, and 4 % other symptoms. Of all subjects, 10 % consulted a doctor and 0.7 % were hospitalized; 18 % took antimicrobials, with TD as the most common indication (64 %). Ongoing symptoms were reported by 25 % of all travelers upon return home. During the three-week follow-up (return rate 51 %), 32 % of respondents developed new-onset symptoms, 20 % visited a doctor and 1.7 % were hospitalized. Factors predisposing to health problems were identified by multivariable analysis: certain regions (Southern Asia, South-Eastern Asia, and Eastern Africa), female gender, young age, and long travel duration. CONCLUSIONS: Despite proper preventive measures like vaccinations, malaria prophylaxis, and travel advice, the majority of our subjects fell ill during or after travel. As the symptoms mostly remained mild, health care services were seldom needed. Typical traveler profiles were identified, thereby providing a tool for pre-travel advice. The finding that one third reported new-onset illness during follow-up attests to the importance of advising clients on potential post-travel health problems already during pre-travel visits. PMID- 27412526 TI - Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis. AB - BACKGROUND: Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses. METHOD: Patients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily. RESULTS: OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05). CONCLUSIONS: These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT01383954 . Registered June 22, 2011. PMID- 27412528 TI - Identification of four novel mutations of the WFS1 gene in Iranian Wolfram syndrome pedigrees. AB - AIMS: Wolfram syndrome is a rare neurodegenerative disorder with an autosomal recessive pattern of inheritance characterized by various clinical manifestations. The related gene, WFS1, encodes a transmembrane glycoprotein, named wolframin. Genetic analyses demonstrated that mutations in this gene are associated with WS type 1. Our aim in this study was to sequence WFS1 coding region in Iranian Wolfram syndrome pedigrees. METHODS: Genomic DNA was extracted from peripheral blood of 12 WS patients and their healthy parents. Exons 2-8 and the exon-intron junctions of WFS1 were sequenced. DNA sequences were compared to the reference using Sequencher software. RESULTS: Molecular analysis of WFS1 revealed six different mutations. Four novel and two previously reported mutations were identified. One novel mutation, c.1379_1381del, is predicted to produce an aberrant protein. A second novel mutation, c.1384G > T, encodes a truncated protein. Novel mutation, c.1097-1107dup (11 bp), causes a frameshift which results in a premature stop codon. We screened for the novel missense mutation, c.1010C > T, in 100 control alleles. This mutation was not found in any of the healthy controls. CONCLUSION: Our study increased the spectrum of WFS1 mutations and supported the role of WFS1 in susceptibility to WS. We hope that these findings open new horizons to future molecular investigations which may help to prevent and treat this devastating disease. PMID- 27412529 TI - Binaural Glimpses at the Cocktail Party? AB - Humans often have to focus on a single target sound while ignoring competing maskers in everyday situations. In such conditions, speech intelligibility (SI) is improved when a target speaker is spatially separated from a masker (spatial release from making, SRM) compared to situations where both are co-located. Such asymmetric spatial configurations lead to a 'better-ear effect' with improved signal-to-noise ratio (SNR) at one ear. However, maskers often surround the listener leading to more symmetric configurations where better-ear effects are absent in a long-term, wideband sense. Nevertheless, better-ear glimpses distributed across time and frequency persist and were suggested to account for SRM (Brungart and Iyer 2012). Here, speech reception was assessed using symmetric masker configurations while varying the spatio-temporal distribution of potential better-ear glimpses. Listeners were presented with a frontal target and eight single-talker maskers in four different symmetrical spatial configurations. Compared to the reference condition with co-located target and maskers, an SRM of up to 6 dB was observed. The SRM persisted when the frequency range of the maskers above or below 1500 Hz was replaced with stationary speech-shaped noise. Comparison to a recent short-time binaural SI model showed that better-ear glimpses can account for half the observed SRM, while binaural interaction utilizing phase differences is required to explain the other half. PMID- 27412530 TI - Reasonable people disagree: lessons learned from the sling and mesh story. PMID- 27412531 TI - Synthetic mesh in pelvic reconstructive surgery: an ongoing saga. PMID- 27412532 TI - Collaboration with the mesh industry: who needs who? AB - Professional physician organisations should be the coordinators of all stakeholders involved in the field of urogynaecology. That means that, together with representatives of the patients ("patient organisations") they develop a priority agenda. This agenda involves the topics that need the highest level of attention, either because knowledge in this area is insufficient, or because existing knowledge is not optimally implemented. The next step is to discuss this list with representatives of industry, patient representatives, insurance companies and organisations with an intention to donate money to women's health. Together, we can design a roadmap for the coming years that involves the top priority topics that need to be dealt with within the available budget. The organisations facilitate the interaction between the different stakeholders, communicate the timetable of these actions not only to their members, but also to society at large. PMID- 27412533 TI - Identification of Positive Allosteric Modulators of Glycine Receptors from a High Throughput Screen Using a Fluorescent Membrane Potential Assay. AB - Glycine receptor 3 (GlyRalpha3) is a ligand-gated ion channel of the cys-loop family that plays a key role in mediating inhibitory neurotransmission and regulation of pain signaling in the dorsal horn. Potentiation of GlyRalpha3 function is therefore of interest as a putative analgesic mechanism with which to target new therapeutics. However, to date, positive allosteric modulators (PAMs) of this receptor with sufficient selectivity to enable target validation studies have not been described. To address this lack of pharmacological tools, we developed a suite of in vitro assays comprising a high-throughput fluorescent membrane potential screen and a medium-throughput electrophysiology assay using IonFlux HT together with conventional manual patch clamp. Using these assays, we conducted a primary screening campaign and report the structures of hit compounds identified as GlyR PAMs. Our functional characterization data reveal a hit compound with high efficacy relative to current known potentiators and selectivity over GABAAR, another major class of inhibitory neurotransmission receptors of importance to pain. These small-molecule GlyR PAMs have high potential both as early tool compounds to enable pharmacological studies of GlyR inhibitory neurotransmission and as a starting point for the development of potent, selective GlyRalpha3 PAMs as novel analgesics. PMID- 27412534 TI - In Vitro Assays for the Discovery of PCSK9 Autoprocessing Inhibitors. AB - PCSK9 plays a significant role in regulating low-density lipoprotein (LDL) cholesterol levels and has become an important drug target for treating hypercholesterolemia. Although a member of the serine protease family, PCSK9 only catalyzes a single reaction, the autocleavage of its prodomain. The maturation of the proprotein is an essential prerequisite for the secretion of PCSK9 to the extracellular space where it binds the LDL receptor and targets it for degradation. We have found that a construct of proPCSK9 where the C-terminal domain has been truncated has sufficient stability to be expressed and purified from Escherichia coli for the in vitro study of autoprocessing. Using automated Western analysis, we demonstrate that autoprocessing exhibits the anticipated first-order kinetics. A high-throughput time-resolved fluorescence resonance energy transfer assay for autocleavage has been developed using a PCSK9 monoclonal antibody that is sensitive to the conformational changes that occur upon maturation of the proprotein. Kinetic theory has been developed that describes the behavior of both reversible and irreversible inhibitors of autocleavage. The analysis of an irreversible lactone inhibitor validates the expected relationship between potency and the reaction end point. An orthogonal liquid chromatography-mass spectrometry assay has also been implemented for the confirmation of hits from the antibody-based assays. PMID- 27412535 TI - Development of a 3D Tissue Culture-Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases. AB - 3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools were developed to process 3D image data to measure over 800 phenotypic parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the phenotypic profiles induced by their respective ligands, hepatocyte growth factor and EGF. The screening method was applied to a novel collection of 80 putative inhibitors of c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of c-Met, EGFR, or bispecific inhibition of both targets. In conclusion, we describe a fully scalable high content screening platform that uses phenotypic profiling to discriminate selective and nonselective (off-target) inhibitors in a physiologically relevant 3D cell culture setting. PMID- 27412536 TI - [Clinical features of childhood purulent meningitis caused by Escherichia coli and Streptococcus pneumoniae: a comparative analysis]. AB - OBJECTIVE: To investigate the differences in clinical features of childhood purulent meningitis (PM) caused by Escherichia coli and Streptococcus pneumoniae, and to provide help for the selection of antibiotics for PM children with unknown etiology. METHODS: A retrospective analysis was performed for the clinical data of children with PM caused by Escherichia coli (12 children) or Streptococcus pneumoniae (15 children). RESULTS: Compared with the Streptococcus pneumoniae infection group, the Escherichia coli infection group had a significantly higher proportion of children with an age of onset of <3 months and a significantly higher incidence rate of convulsion, but significantly lower incidence rates of severe fever (>39 degrees C) and disturbance of consciousness and a significantly lower proportion of children with an increased leukocyte count at diagnosis (>12*10(9)/L). The results of routine cerebrospinal fluid test and biochemical examinations showed no significant differences between the two groups. Escherichia coli and Streptococcus pneumoniae were resistant to cephalosporins and had a sensitivity to chloramphenicol more than 90%. Escherichia coli was fully sensitive to meropenem and Streptococcus pneumoniae was fully sensitive to vancomycin. CONCLUSIONS: PM caused by Escherichia coli and Streptococcus pneumoniae has different clinical features. As for PM children with severe fever, disturbance of consciousness, and an increased leukocyte count, the probability of Streptococcus pneumoniae infection should be considered. For PM children with an age of onset of <3 months, medium- and low-grade fever, frequent convulsions, and a leukocyte count of <12*10(9)/L, the probability of Escherichia coli infection should be considered. PMID- 27412537 TI - [Effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children]. AB - OBJECTIVE: To investigate the effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children and the risk factors for cognitive impairment. METHODS: A retrospective analysis was performed for the clinical data of 38 children with temporal lobe epilepsy and 40 children with idiopathic epilepsy. The controls were 42 healthy children. All subjects received the following neuropsychological tests: Montreal Cognitive Assessment (MoCA) scale, verbal fluency test, digit span test, block design test, Social Anxiety Scale for Children (SASC), and Depression Self-rating Scale for Children (DSRSC). RESULTS: Compared with the control group, the temporal lobe epilepsy and idiopathic epilepsy groups showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). Compared with the idiopathic epilepsy group, the temporal lobe epilepsy group showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). In the temporal lobe epilepsy group, MoCA score was negatively correlated with SASC score, DSRSC score, and seizure frequency (r= 0.571, -0.529, and -0.545 respectively; P<0.01). In the idiopathic epilepsy group, MoCA score was also negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.542, -0.487, and -0.555 respectively; P<0.01). CONCLUSIONS: Children with temporal lobe epilepsy and idiopathic epilepsy show impaired whole cognition, verbal fluency, memory, and executive function and have anxiety and depression, which are more significant in children with temporal lobe epilepsy. High levels of anxiety, depression, and seizure frequency are risk factors for impaired cognitive function. PMID- 27412538 TI - [Lamotrigine monotherapy in children with epilepsy: a systematic review]. AB - OBJECTIVE: To investigate the efficacy and safety of lamotrigine monotherapy in children with epilepsy via a systematic review. METHODS: PubMed, Cochrane, CNKI, VIP, CBM, Wanfang Data were searched for randomized controlled trials (RCTs) of lamotrigine monotherapy in children with epilepsy. Literature screening, data extraction, and quality assessment were performed according to the method recommended by Cochrane Collaboration. RevMan 5.2 software was used to conduct the Meta analysis. RESULTS: A total of 9 RCTs involving 1 016 participants were included. Lamotrigine yielded a significantly lower complete control rate of seizure than ethosuximide, but the complete control rate of seizure showed no significant differences between lamotrigine and carbamazepine/sodium valproate. Patients treated with lamotrigine had a significantly lower incidence rate of adverse events than those treated with carbamazepine, but the incidence rate of adverse events showed no significant differences between patients treated with lamotrigine and sodium valproate/carbamazepine. The drop-out rate showed no significant differences between the three treatment groups. CONCLUSIONS: Lamotrigine is an ideal alternative drug for children who do not respond to traditional antiepileptic medication or experience significant adverse reactions; however, more high-quality RCTs with a large sample size and a long follow-up time are needed to confirm these conclusions. PMID- 27412539 TI - [Characteristics of attention in school-age children with mild autism spectrum disorder]. AB - OBJECTIVE: To investigate the characteristics of attention in school-age children with mild autism spectrum disorder (ASD), and to provide a basis for clinical treatment. METHODS: A total of 20 school-age children with mild ASD were enrolled, and the intermediate visual and auditory continuous performance test (IVA-CPT) was used to assess their attention. A total of 20 children with attention deficit hyperactivity disorder (ADHD) and 40 healthy children were enrolled as controls. RESULTS: Compared with the normal control group, the ASD group showed significantly lower scores of full scale attention quotient, full scale response control quotient, visual/auditory full scale response control quotient, visual/auditory prudence quotient, auditory perseverance quotient, visual consistency quotient, visual/auditory vigilance quotient, visual attention quotient, visual speed quotient, number of correct visual/auditory reactions, and visual mean reaction time of the second and third phases (P<0.05). Compared with the ADHD group, the ASD group showed significantly higher scores of full scale response control quotient and auditory consistency quotient (P<0.05), as well as significantly lower scores of visual vigilance quotient and visual speed quotient (P<0.05). CONCLUSIONS: School-age children with mild ASD have attention deficit mainly manifested as the defect in the ability to focus attention, which is similar to the defect in children with ADHD, but ASD children have a lower degree of attention control impairment compared with children with ADHD. The defect in the ability to focus visual attention is more severe than that in the ability to focus auditory attention, while there is no significant difference between the defects in visual and auditory attention control. PMID- 27412540 TI - [Correlation between event-related potential and behavioral problems in early school-age children with attention deficit hyperactivity disorder]. AB - OBJECTIVE: To investigate the cognitive characteristics in early school-age children with attention deficit hyperactivity disorder (ADHD) using event-related potential (ERP) and Achenbach Child Behavior Checklist (CBCL), as well as the correlation between ERP and behavioral problems. METHODS: A total of 22 children aged 6-7 years with ADHD and 19 healthy children matched by age were enrolled. Continue Performance Test-AX (CPT-AX) was performed for ERP test. The amplitude and latency of N2 and P3 of Go and Nogo were compared. The CBCL was completed by the parents, and the correlation between behavioral factors and ERP was analyzed. RESULTS: The ADHD group had a significantly higher number of ERP omissions than the normal control group (10+/-8 vs 5+/-4; P<0.05), while the reaction time and number of commission errors showed no significant differences between the two groups (P>0.05). The ADHD group showed a significantly lower Go-N2 amplitude than the normal control group (-8+/-5 MUV vs -10+/-4 MUV; P<0.05). In the ADHD group, the detection rates of hyperactivity, attack, and discipline violation were 27%, 27% and 9% respectively. The scores on attack and discipline violation subscales were negatively correlated with the Go-N2 amplitude of ERP (r=-0.43 and -0.48 respectively; P<0.05), while the score on hyperactivity subscale was positively correlated with the latency of Go-P3 (r=0.50, P<0.05). CONCLUSIONS: The early school-age children with ADHD show the tendency to the impairment of attention/executive function, but the inhibition function defect has not been noted. In early school-age children with ADHD, the behavioral problems such as hyperactivity, attack, and discipline violation are associated with ERP. PMID- 27412541 TI - [Diagnostic values of plasma CD64 and sTREM-1 for pediatric pneumonia]. AB - OBJECTIVE: To determine the diagnostic values of plasma CD64 and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in children with pneumonia. METHODS: Sixty children with pneumonia between August 2014 and October 2015 were classified into bacterial pneumonia group (25 cases), viral pneumonia group (17 cases), and Mycoplasma pneumonia group (18 cases) according to their clinical manifestations, pathogen cultures, and X-ray findings. Another 30 healthy children who underwent physical examination during the same period were selected as the control group. The concentrations of CD64 and sTREM-1 in blood samples were determined using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic sensitivity and specificity of plasma CD64 and/or sTREM-1 for bacterial pneumonia. RESULTS: The expression of CD64 and sTREM-1 in the bacterial pneumonia group was significantly higher than that in the viral pneumonia, Mycoplasma pneumonia, and control groups (P<0.05). The areas under the ROC curves of CD64, sTREM-1, and a combination of the two markers for diagnosing bacterial pneumonia were 0.878, 0.805, and 0.956, respectively. The sensitivity and specificity of CD64 for diagnosing bacterial pneumonia were 81.30% and 92.32%, respectively, when the cut-off value was 641 pg/mL. The sensitivity and specificity of sTREM-1 for diagnosing bacterial pneumonia were 78.65% and 84.67%, respectively, when the cut-off value was 1 479 pg/mL. The sensitivity and specificity of a combination of the two markers for diagnosing bacterial pneumonia were 93.15% and 91.54%, respectively. CONCLUSIONS: Plasma CD64 and sTREM-1 can be used as markers for diagnosing pediatric bacterial pneumonia, and a combination of the two markers results in better diagnosis. PMID- 27412542 TI - [Change in serum intestinal fatty acid binding protein and its significance in children with pneumonia and gastrointestinal injury]. AB - OBJECTIVE: To study the change in serum intestinal fatty acid binding protein (IFABP) in children with pneumonia and its correlation with gastrointestinal injury. METHODS: A total of 82 children with community-acquired pneumonia who were treated from January to October, 2015 were enrolled, among whom 34 had mild pneumonia and 48 had severe pneumonia. According to pediatric critical illness score (PCIS), the children with severe pneumonia were further divided into non critical group (25 patients) and critical group (23 patients). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. ELISA was used to measure serum IFABP level, and the acute gastrointestinal injury (AGI) grade was determined for children with severe pneumonia. Serum IFABP level was compared between groups, and the correlations of IFABP with AGI grade and PCIS were analyzed. RESULTS: The severe pneumonia group showed a significantly higher serum IFABP level than the control group and the mild pneumonia group (P<0.01), and the mild pneumonia group also showed a significantly higher serum IFABP level than the control group (P<0.01). The critical group showed a significantly higher serum IFABP level than the non critical group (P<0.01). The patients with grade I-IV AGI had significantly higher serum IFABP levels than the control group (P<0.01), and the serum IFABP level increased significantly with the increasing AGI grade (P<0.01). Serum IFABP level was positively correlated with AGI grade (P<0.01) but negatively correlated with PCIS (P<0.01). CONCLUSIONS: Children with pneumonia experience an increased serum IFABP level which can be used as a sensitive indicator for the early diagnosis of gastrointestinal injury and the evaluation of conditions in children with pneumonia. PMID- 27412543 TI - [Distribution characteristics of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in hospitalized children with acute respiratory tract infection: an analysis of 13 198 cases]. AB - OBJECTIVE: To investigate the distribution characteristics of Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), and Legionella pneumophila (LP) in hospitalized children with acute respiratory tract infection (ARTI). METHODS: A total of 13 198 hospitalized children with ARTI were enrolled as study subjects. Whole blood and urine were collected. The passive agglutination was used to detect serum MP-IgM, ELISA was used to detect serum CP-IgM, and immunochromatography was performed to detect urinary LP antigen. RESULTS: Among the 13 198 hospitalized ARTI children, the detection rates of MP, CP, and LP were 25.31%, 12.74% and 3.27%, suggesting that MP had the highest detection rate (P<0.0125). The detection rates of MP in 2013 and 2014 were significantly higher than that in 2012 (P<0.0125). CP had the highest detection rate in 2013, and LP had the highest detection rate in 2014 (P<0.0125). These three pathogens were detected all around the year, and MP had the highest detection rate in all seasons (P<0.0125). The detection rate of mixed infection with three pathogens was 4.35%, and mixed infection with MP and CP was the most common (P<0.0071). Among the children in different age groups, the patients aged 5-16 years showed the highest overall detection rate of three pathogens (P<0.0071). Among the children with different types of ARTI, the children with bronchopneumonia showed the highest overall detection rate of three pathogens (P<0.0045). CONCLUSIONS: MP, CP, and LP, particularly MP, are important pathogens for children with ARTI in the local area. LP infection tends to increase year by year and should be taken seriously in clinical practice. PMID- 27412544 TI - [Expression profiles of PI3K, NF-kappaB, and STAT1 in peripheral blood mononuclear cells in children with bronchial asthma]. AB - OBJECTIVE: To study the expression profiles of PI3K, NF-kappaB, and STAT1 in peripheral blood mononuclear cells (PBMCs) in children with bronchial asthma, as well as their roles in the pathogenesis of asthma. METHODS: Thirty children with acute exacerbation of bronchial asthma were enrolled as the asthma group, and 20 healthy children were enrolled as the control group. RT-PCR and Western blot were used to measure the mRNA and protein expression levels of PI3K, NF-kappaB, and STAT1 in PBMCs. A spirometer was used to compare the pulmonary function between the two groups. The correlations between the mRNA expression of PI3K, NF-kappaB, and STAT1 and pulmonary function in children with bronchial asthma were analyzed. RESULTS: The asthma group had significantly higher mRNA and protein expression levels of PI3K, NF-kappaB, and STAT1 than the control group (P<0.05). Compared with the control group, the asthma group showed significant reductions in pulmonary function indices such as FEV1%, FEV1/FVC, and PEF% (P<0.05). In children with bronchial asthma, the mRNA expression levels of PI3K, NF-kappaB, and STAT1 were negatively correlated with FEV1%, FEV1/FVC, and PEF% (P<0.05). CONCLUSIONS: The expression levels of PI3K, NF-kappaB, and STAT1 increase in children with asthma, and are negatively correlated with pulmonary function indices, suggesting that PI3K, NF-kappaB and STAT1 are involved in the development and progression of bronchial asthma in children. PMID- 27412545 TI - [Prevalence of Helicobacter pylori cagA, vacA, and iceA genotypes in children with gastroduodenal diseases]. AB - OBJECTIVE: To investigate the prevalence of cagA, vacA, and iceA genotypes in the isolated strains of Helicobacter pylori (H.pylori) from children with gastroduodenal diseases in Jiangxi, China, as well as the association between cagA, vacA, and iceA genotypes and the type of gastroduodenal diseases. METHODS: The samples of gastric antral mucosa were collected from 316 children with gastroduodenal diseases in Jiangxi, and a total of 107 strains of H.pylori were isolated. The genomic DNA of these strains was extracted, and PCR was used to determine the ureA, cagA, vacA, and iceA genotypes. RESULTS: Of all the 107 isolated strains of H.pylori, the detection rates of ureA and cagA genes were 100% (107/107) and 94.4% (101/107) respectively. The overall detection rate of vacA gene was 100% (107/107), and the detection rates of vacAs1a, vacAs1c, vacAm1, and vacAm2 genes were 74.8% (80/107), 25.2% (27/107), 29.9% (32/107), and 69.2% (74/107) respectively, with both vacAm1 and vacAm2 genes detected in 0.9% (1/107) of all H.pylori strains. In the chimera of vacA gene, the detection rates of vacAs1a/m1, vacAs1a/m2, vacAs1c/m1, and vacAs1c/m2 genes were 26.2% (28/107), 51.4% (55/107), 3.7% (4/107), and 17.8% (19/107) respectively (P<0.001). The detection rates of iceA1 and iceA2 genes were 79.4% (85/107) and 9.3% (10/107), respectively (P<0.001), and both iceA1 and iceA2 genes were detected in 7.5% (8/107) of all strains. The detection rates of the genotypes of H.pylori showed no significant differences between the peptic ulcer, chronic gastritis, and duodenal bulbar inflammation groups (P>0.05). CONCLUSIONS: The dominant genotypes of H.pylori are cagA, vacAs1a/m2, and iceA1, and there are mixed infections with H.pylori strains of different genotypes in children with gastroduodenal disease from Jiangxi, China. The genotypes of H.pylori are not associated with the type of gastroduodenal disease. PMID- 27412546 TI - [Association of Cosmc gene mutation with susceptibility to Henoch-Schonlein purpura in children]. AB - OBJECTIVE: To investigate the presence of Cosmc gene mutation in children with Henoch-Schonlein purpura (HSP) and the association between Cosmc gene mutation and the susceptibility to HSP. MESULTS: Eighty-four children who were diagnosed with HSP between March 2014 and December 2015 were selected as the HSP group. Fifty-eight healthy volunteers matched for age and sex were enrolled as the control group. Fasting venous blood (5 mL) from the two groups was collected in EDTA anticoagulated tubes, followed by the isolation of peripheral blood mononuclear cells (PBMCs) through density gradient centrifugation. Genomic DNA was extracted from PBMCs according to the manufacturer's protocol, and the whole exon region of Cosmc gene was amplified by touch-down polymerase chain reaction (touch-down PCR). The PCR products were identified by 1% agarose gel and sequenced in order to further examine the association between Cosmc gene mutation and the susceptibility to HSP. RESULTS: Sequencing results showed two mutations (c.393T>A and c.72A>G) of Cosmc gene in children with HSP. There were no significant differences in the genotype and allele frequencies at the two loci between the HSP and control groups, and this distribution was not associated with sex. CONCLUSIONS: The mutations c.393T>A and c.72A>G in the exon region of Cosmc gene in children with HSP are not associated with the onset of HSP. PMID- 27412547 TI - [Detection of gene mutation in glucose-6-phosphate dehydrogenase deficiency by RT PCR sequencing]. AB - OBJECTIVE: Since glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary hemolytic erythrocyte enzyme deficiency, most cases have single nucleotide mutations in the coding region, and current test methods for gene mutation have some missed detections, this study aimed to investigate the feasibility of RT-PCR sequencing in the detection of gene mutation in G6PD deficiency. METHODS: According to the G6PD/6GPD ratio, 195 children with anemia of unknown cause or who underwent physical examination between August 2013 and July 2014 were classified into G6PD-deficiency group with 130 children (G6PD/6GPD ratio <1.00) and control group with 65 children (G6PD/6GPD ratio>=1.00). The primer design and PCR amplification conditions were optimized, and RT-PCR sequencing was used to analyze the complete coding sequence and verify the genomic DNA sequence in the two groups. RESULTS: In the G6PD-deficiency group, the detection rate of gene mutation was 100% and 13 missense mutations were detected, including one new mutation. In the control group, no missense mutation was detected in 28 boys; 13 heterozygous missense mutations, 1 homozygous same sense mutation (C1191T) which had not been reported in China and abroad, and 14 single nucleotide polymorphisms of C1311T were detected in 37 girls. The control group showed a high rate of missed detection of G6PD deficiency (carriers) in the specimens from girls (35%, 13/37). CONCLUSIONS: RT-PCR sequencing has a high detection rate of G6PD gene mutation and a certain value in clinical diagnosis of G6PD deficiency. PMID- 27412548 TI - [Influence of delayed cord clamping on preterm infants with a gestational age of <32 weeks]. AB - OBJECTIVE: To investigate the influence of delayed cord clamping (DCC) on preterm infants with a gestational age of <32 weeks. METHODS: Ninety preterm infants with a gestational age of <32 weeks delivered naturally from January to December, 2015 were enrolled and randomly divided into DCC group (46 infants) and immediate cord clamping (ICC) group (44 infants). The routine blood test results, total amount of red blood cell transfusion, blood gas parameters, mean arterial pressure, bilirubin peak, total time of phototherapy, and incidence rates of necrotizing enterocolitis, late-onset sepsis, intracranial hemorrhage, retinopathy, and bronchopulmonary dysplasia were compared between the two groups. RESULTS: Compared with the ICC group, the DCC group had significantly higher levels of hemoglobin, hematocrit, mean arterial pressure, and standard base excess (P<0.05), as well as a significantly lower percentage of preterm infants who underwent volume expansion and dopamine treatment and a significantly lower amount of red blood cell transfusion (P<0.05). The body temperature, pH value, HCO3(-) concentration, serum bilirubin peak, total time of phototherapy, and incidence rates of late-onset sepsis, retinopathy, grade>=2 intracranial hemorrhage, and grade>=2 neonatal necrotizing enterocolitis showed no significant differences between the two groups (P>0.05). CONCLUSIONS: DCC is a safe clinical intervention and can improve the prognosis of preterm infants with a gestational age of <32 weeks. PMID- 27412549 TI - [Association between development of hypertension and nutrition in school-age children in Fengdu County of Chongqing, China]. AB - OBJECTIVE: To investigate the association between the development of hypertension and nutrition in school-age children in Fengdu County of Chongqing, China. METHODS: A total of 8 033 children from 2 public primary schools in Fengdu County of Chongqing, whose registered residence was in the subdistricts where the two schools were located, were selected as study subjects using cluster random sampling. Body height, body weight, and blood pressure were measured, and the semi-quantitative food frequency questionnaire was used for dietary survey. The association between body mass index (BMI), dietary nutrients, and the development of hypertension in children was analyzed. RESULTS: A total of 7 538 children were enrolled for analysis. The detection rates of obesity, overweight, and hypertension were 9.11%, 12.27%, and 11.83% respectively. In children with obesity and overweight, the detection rate of hypertension was 33.62% and 17.84% respectively, 4.02 and 2.13 times that in normal children. The multivariate logistic stepwise regression analysis revealed that increased intake of calcium and sodium increased the risk of hypertension (OR=1.003 and 1.002 respectively), while the increased iron intake and calcium intake per unit body weight reduced the risk of hypertension (OR=0.979 and 0.926 respectively). CONCLUSIONS: The prevalence of hypertension and obesity in school-age children in Fengdu County of Chongqing is high. BMI and dietary nutrients are closely associated with the development of hypertension in children. Active control of body weight, adjustment of dietary structure, and limitation of sodium intake should be adopted to reduce the development of hypertension in school-age children. PMID- 27412550 TI - [Effect of motivational interviewing combined with peer participation on obesity management in adolescents]. AB - OBJECTIVE: To investigate the effect of motivational interviewing combined with peer participation on obesity management in adolescents. METHODS: A total of 100 adolescents with simple obesity were randomly divided into traditional management and peer participation groups (n=50 each). The traditional management group received traditional health management. The peer participation group received motivational interviewing performed by psychological consultants combined with peer participation through the entire process in addition to traditional health management. The physical exercise, dietary behavior, differences in body composition parameters, and effect of comprehensive intervention were compared between the two groups after intervention for half a year. RESULTS: After the health management for six months, the peer participation group showed better improvements in the control of energy intake, adjustment of dietary structure, adherence to moderate/high intensity exercise, and increase in lean body mass compared with the traditional management group (P<0.05). The peer participation group had a significantly higher attendance rate for guidance and counseling performed by a multidisciplinary team once a week than the traditional management group (89% vs 57%; P<0.05), as well as a significantly higher response rate to health management than the traditional management group (83% vs 43%; P<0.05). CONCLUSIONS: Motivational interviewing combined with peer participation for obesity management can improve the compliance and the effect of comprehensive intervention in losing weight in adolescents. PMID- 27412551 TI - [17beta-estradiol suppresses hyperoxia-induced apoptosis of oligodendrocyte precursor cells through paired-immunoglobulin-like receptor B]. AB - OBJECTIVE: To study the effect of hyperoxia and paired immunoglobin-like receptor B (PirB) on rat oligodendrocyte precursor cells (OPCs) in vivo and the neuroprotective effects of 17beta-estradiol (E2) on these cells. METHODS: Rat OPCs were treated with different concentrations of E2 and the cells were harvested for RT-qPCR analysis at different time points. PriB was silenced with small interfering siRNA. The effects of E2 treatment and silencing of PriB on OPCs viability and apoptosis under hyperoxic stimulation were detected using 3 (4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. RESULTS: Hyperoxia induced apoptosis in OPCs and decreased their viability. E2 treatment markedly down-regulated the expression of PirB. E2 treatment or PirB silencing markedly decreased hyperoxia-induced apoptosis and increased cell viability in OPCs. CONCLUSIONS: E2 can protect OPCs from hyperoxia induced apoptosis. PMID- 27412552 TI - [Immunoregulatory effect of adipose-derived stem cell transplantation in young mouse model of food allergy]. AB - OBJECTIVE: To investigate the immunoregulatory effect of adipose-derived stem cell (ADSC) transplantation by intraperitoneal injection in food-allergic young mice before and after ovalbumin (OVA) sensitization. METHODS: Thirty-two 3-week old female Balb/c mice were randomly divided into control, allergic model, ADSC treatment, and ADSC prevention groups (n=8 each). A young mouse model of food allergy was established by OVA sensitization via intraperitoneal injection. Each mouse from the prevention and treatment groups was transplanted with 1*10(6) ADSCs on days 1 and 15 post-sensitization, respectively. The allergic symptoms of all groups were observed and scored. The jejunal villi and inflammatory cell infiltration were observed by hematoxylin-eosin staining. Serum levels of allergy related inflammatory cytokines were measured by Luminex. RESULTS: Compared with the allergic model group, the ADSC prevention and ADSC treatment groups had significantly reduced allergic symptom scores (P<0.05). The two groups also showed significantly alleviated allergic pathological damage of the jejunal mucosa. Serum levels of interleukin (IL)-4, IL-5, IL-6, IL-17A, IL-22 and IL-23 were significantly lower in the ADSC prevention and treatment groups than in the allergic model group (P<0.05). However, the ADSC treatment group had a significantly increased serum interferon-gamma level and a significantly reduced serum monocyte chemotactic protein-1 level compared with the allergic model and ADSC prevention groups (P<0.05). CONCLUSIONS: ADSC transplantation, performed before or after sensitization, has an immunoregulatory effect on food allergy in young Balb/c mice, but this effect is better if transplantation is performed after sensitization. PMID- 27412553 TI - [Identification of bocavirus infection in a young child with pneumonia using a pan-microbial microarray]. PMID- 27412554 TI - [Research advances in the relationship between cow's milk allergy and gastroesoph ageal reflux in infants]. AB - Gastroesophageal reflux (GER) and cow's milk allergy (CMA) are common disorders in infants. In recent years, more and more research has investigated the relationship between these two diseases. Some studies reported that about half of the cases of GER in infants younger than 1 year may be an association with CMA. Therefore, overall understanding the role of CMA on the pathogenesis of GER has a great importance on improving clinical level of diagnosis and therapy. This review article tried to elaborate advances in research on the relationship between CMA and GER in infants, including epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment. PMID- 27412555 TI - [Research advances in association between pediatric obesity and bronchial asthma]. AB - This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor. PMID- 27412557 TI - Retraction Note to: Platelet-derived growth factor-D contributes to aggressiveness of breast cancer cells by up-regulating Notch and NF-kappaB signaling pathways. PMID- 27412556 TI - SREBP1c-CRY1 signalling represses hepatic glucose production by promoting FOXO1 degradation during refeeding. AB - SREBP1c is a key lipogenic transcription factor activated by insulin in the postprandial state. Although SREBP1c appears to be involved in suppression of hepatic gluconeogenesis, the molecular mechanism is not thoroughly understood. Here we show that CRY1 is activated by insulin-induced SREBP1c and decreases hepatic gluconeogenesis through FOXO1 degradation, at least, at specific circadian time points. SREBP1c(-/-) and CRY1(-/-) mice show higher blood glucose than wild-type (WT) mice in pyruvate tolerance tests, accompanied with enhanced expression of PEPCK and G6Pase genes. CRY1 promotes degradation of nuclear FOXO1 by promoting its binding to the ubiquitin E3 ligase MDM2. Although SREBP1c fails to upregulate CRY1 expression in db/db mice, overexpression of CRY1 attenuates hyperglycaemia through reduction of hepatic FOXO1 protein and gluconeogenic gene expression. These data suggest that insulin-activated SREBP1c downregulates gluconeogenesis through CRY1-mediated FOXO1 degradation and that dysregulation of hepatic SREBP1c-CRY1 signalling may contribute to hyperglycaemia in diabetic animals. PMID- 27412558 TI - Retraction Note to: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra cellular matrix degrading factors. PMID- 27412559 TI - Prenatal care and childbirth assistance in Amazonian women before and after the Pacific Highway Construction (2003-2011): a cross-sectional study. AB - BACKGROUND: Attention to prenatal care and child delivery is important for the health of women and children, but in the Amazon these indicators tend to be historically unfavorable, in part by geographical and political isolation. In 2003 both Brazilian and Peru governments have finished paving an international road connecting remotes areas in the Brazilian Amazon to the Pacific coast in Peru. METHODS: The situation of prenatal care and child delivery with mothers of children under 5 years old living in the urban area of Assis Brasil, Acre was assessed in two cross-sectional studies performed in 2003 and 2011, corresponding to the period before and after the Pacific highway construction. RESULTS: In 2003, most mothers were of black/Afro-American ethnicity, or "pardos" (the offspring of a Caucasian with a African descendant) (77.69 %), had more than 4 years of schooling (73.40 %) and had a mean age of 22.18 years. In 2011, the number of as a migration of indigenous women increased from 0 to 14.40 % of the respondents, because of migration from communities along the rivers to urban areas, with no other significant changes in maternal characteristics. No significant improvement in childbirth assistance was noticed between 1997 and 2011; only the percentage of in-hospital vaginal deliveries performed by doctors increased from 17.89 to 66.26 % (p <0.001) during this period. Access to prenatal care was associated with white ethnicity in 2003, and higher socioeconomic level and white ethnicity in 2011, while the higher number of prenatal visits was associated with higher maternal education and higher socioeconomic levels in 2011. Vaginal child delivery at a hospital facility was associated with maternal age in 2003, and year of birth, being of white ethnicity and higher level of education in 2011. CONCLUSIONS: The indicators of prenatal care and child delivery were below the national average, showing that geographical isolation still affects women's health care in the Amazon, despite the construction of the highway and governmental health protocols adopted during this period. PMID- 27412560 TI - Primary rhabdomyosarcoma of the distal femoral diaphysis: a case report and review of the literature. AB - Primary rhabdomyosarcoma of the bone is an extremely rare condition with few examples reported in the literature. We present the case of a 34-year-old male who presented with a lesion in the distal femur with initial imaging features consistent with Ewing sarcoma. Histologically, the lesion consisted of atypical pleomorphic polygonal rhabdomyoblasts demonstrating focal desmin and myogenin expression. A diagnosis of pleomorphic rhabdomyosarcoma was rendered. Despite systemic treatment and surgery, this patient experienced a rapidly progressive disease course. We believe this is only the second report in the orthopedic literature of a case of primary pleomorphic rhabdomyosarcoma of the bone. The key imaging, pathologic, and clinical findings are discussed. PMID- 27412563 TI - Communicating Uncertain News in Cancer Consultations. AB - In cancer communication, most of the literature is in the realm of delivering bad news while much less attention has been given to the communication of uncertain news around the diagnosis and the possible outcomes of the illness. Drawing on video-recorded cancer consultations collected in two Italian hospitals, this article analyzes three communication practices used by oncologists to interactionally manage the uncertainty during the visit: alternating between uncertain bad news and certain good news, anticipating scenarios, and guessing test results. Both diagnostic and personal uncertainties are not hidden to the patient, yet they are reduced through these practices. Such communication practices are present in 32 % of the visits in the data set, indicating that the interactional management of uncertainty is a relevant phenomenon in oncological encounters. Further studies are needed to improve both its understanding and its teaching. PMID- 27412561 TI - miR-145 mediated the role of aspirin in resisting VSMCs proliferation and anti inflammation through CD40. AB - BACKGROUND: Aspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; however, the mechanisms by which ASA exerts its anti proliferative effect remain not fully understood. This study was designed to investigate whether miR-145 is involved in the regulation of vascular smooth muscle cells' (VSMCs) proliferation and to determine the anti-inflammatory effects of ASA via its regulation of CD40 to provide a new theoretical basis for the pharmacological effect of aspirin. METHODS: The TNF-alpha induced proliferation model of VSMCs was divided into different groups with or without aspirin. Cell proliferation was detected by EdU; Real-time PCR was used to detect the mRNA expression of miR-145, CD40, and Calponin, a VSMCs differentiation marker gene. Western blot was used to detect the protein expression of CD40; ELISA was used to determine the concentrations of the inflammatory cytokine IL-6 in cell supernatants. RESULTS: The proliferation of VSMCs was stimulated by TNF alpha and accompanied by decreased levels of Calponin. TNF-alpha also decreased the levels of miR-145 and increased the levels of CD40 and IL-6. Pretreatment with 20 MUg/mL of aspirin in VSMCs could partially block the above-mentioned effects induced by TNF-alpha. The protective effects of ASA in VSMCs were reversed by a pretreatment with a miR-145 inhibitor. We also found that the expression of miR-145 in peripheral blood mononuclear cells in ischemic stroke patients was significantly increased after a 10-day treatment with aspirin. CONCLUSION: miR-145 is involved in the anti-proliferation and anti-inflammation effects of aspirin on VSMCs by inhibiting the expression of CD40. PMID- 27412562 TI - A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer. AB - BACKGROUND: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. METHODS: Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. RESULTS: Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60 , and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. CONCLUSION: Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010. PMID- 27412564 TI - LDL-C/HDL-C ratio and risk of all-cause mortality in patients with intracerebral hemorrhage. AB - BACKGROUND: The low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio has been recognized as a strong risk predictor of cardiovascular diseases. However, the association between the LDL-C/HDL-C ratio and the prognosis of acute intracranial hemorrhage (ICH) is unclear. Thus, we prospectively investigated whether a low LDL-C/HDL-C ratio could predict all cause mortality and whether LDL-C/HDL-C ratio is superior to traditional lipid profiles in predicting mortality among Chinese patients with acute ICH. METHODS: A prospective cohort study of 356 patients with acute ICH was conducted, and the mean follow-up time point was 80.4 days. Participants were divided into four categories based on LDL-C/HDL-C ratio quartiles. Three-month outcomes were evaluated by in-person or telephone interviews with patients or their family members. The end point was three-month mortality from all causes. RESULTS: Forty seven deaths from all causes were documented. The multivariate analysis found that LDL-C/HDL-C ratio [hazard ratio (HR) = 0.49, p = 0.008] and LDL-C (HR = 0.27, p = 0.044) were significantly associated with all-cause mortality. The Kaplan-Meier curves show that patients in the lowest quartiles had the highest cumulative incidence rates (log-rank p = 0.027). After adjusting for covariates, a low LDL-C/HDL-C ratio was associated with a 3.55-fold increase in the risk of all-cause mortality (HR, 3.55 [95% confidence interval, 1.04-12.14]; P-trend = 0.011) when the highest and lowest quartiles were compared. The C-statistic of the LDL-C/HDL-C ratio was significantly larger than other traditional lipid profiles (all p < 0.05). CONCLUSIONS: A low LDL-C/HDL-C ratio was independently associated with an increased risk of all-cause mortality at three months in patients with ICH. Moreover, the LDL-C/HDL-C ratio appeared to be a best lipid predictor of all-cause mortality than traditional lipid profiles. PMID- 27412565 TI - Head computed tomographic measurement as a predictor of outcome in patients with subdural hematoma with cerebral edema. AB - BACKGROUND: The ability to predict outcome in patients with cerebral edema is important because it can influence treatment strategy. We evaluated whether differences in head computed tomographic (CT) measurements in Hounsfield units (HU) of white matter and gray matter can be used as a predictor of outcome in patients with subdural hematoma with cerebral edema. METHODS: We evaluated 34 patients who had subdural hematoma with cerebral edema following acute closed head trauma and had undergone head CT within a few hours of admission. We divided them into the survival (n = 24) group and death (n = 10) group, and measured the HU of white matter and gray matter at injury and non-injury sites. RESULTS: There were no significant differences in operation time or blood loss during surgery between the two groups. Only the HU of white matter in the injury site of patients in the death group were decreased significantly. A cut-off value of 31.5 for HU of white matter showed 80.0 % sensitivity and 99.9 % specificity for death; the area under the curve was 0.91. DISCUSSION: Our results are more evidence of the support of neurogenic edema in trauma rather than an important clinical tool at this stage. However, HU values in WM may be one factor in the decision-making process that affects patient outcome. Changing the treatment strategy in patients with a low HU value in the WM at the injury site may bring about an improvement in patient outcome. CONCLUSION: Measurement in HU of white matter at the injury site might be useful as a predictor of outcome in patients with subdural hematoma with cerebral edema. PMID- 27412567 TI - Percolation-based precursors of transitions in extended systems. AB - Abrupt transitions are ubiquitous in the dynamics of complex systems. Finding precursors, i.e. early indicators of their arrival, is fundamental in many areas of science ranging from electrical engineering to climate. However, obtaining warnings of an approaching transition well in advance remains an elusive task. Here we show that a functional network, constructed from spatial correlations of the system's time series, experiences a percolation transition way before the actual system reaches a bifurcation point due to the collective phenomena leading to the global change. Concepts from percolation theory are then used to introduce early warning precursors that anticipate the system's tipping point. We illustrate the generality and versatility of our percolation-based framework with model systems experiencing different types of bifurcations and with Sea Surface Temperature time series associated to El Nino phenomenon. PMID- 27412566 TI - While we dither, people continue to die from overdose: Comments on 'Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?'. PMID- 27412569 TI - EXtended ACquisition Time (EXACT) NMR-A Case for 'Burst' Non-Uniform Sampling. AB - A strong case exists for the introduction of burst non-uniform sampling (NUS) in the direct dimension of NMR spectroscopy experiments. The resulting gaps in the NMR free induction decay can reduce the power demands of long experiments (by switching off broadband decoupling for example) and/or be used to introduce additional pulses (to refocus homonuclear coupling, for example). The final EXtended ACquisition Time (EXACT) spectra are accessed by algorithmic reconstruction of the missing data points and can provide higher resolution in the direct dimension than is achievable with existing non-NUS methods. PMID- 27412568 TI - Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics. AB - Intramammary infection leading to bovine mastitis is the leading disease problem affecting dairy cows and has marked effects on the milk produced by infected udder quarters. An experimental model of Streptococcus uberis mastitis has previously been investigated for clinical, immunological and pathophysiological alteration in milk, and has been the subject of peptidomic and quantitative proteomic investigation. The same sample set has now been investigated with a metabolomics approach using liquid chromatography and mass spectrometry. The analysis revealed over 3000 chromatographic peaks, of which 690 were putatively annotated with a metabolite. Hierarchical clustering analysis and principal component analysis demonstrated that metabolite changes due to S. uberis infection were maximal at 81 hours post challenge with metabolites in the milk from the resolution phase at 312 hours post challenge being closest to the pre challenge samples. Metabolic pathway analysis revealed that the majority of the metabolites mapped to carbohydrate and nucleotide metabolism show a decreasing trend in concentration up to 81 hours post-challenge whereas an increasing trend was found in lipid metabolites and di-, tri- and tetra-peptides up to the same time point. The increase in these peptides coincides with an increase in larger peptides found in the previous peptidomic analysis and is likely to be due to protease degradation of milk proteins. Components of bile acid metabolism, linked to the FXR pathway regulating inflammation, were also increased. Metabolomic analysis of the response in milk during mastitis provides an essential component to the full understanding of the mammary gland's response to infection. PMID- 27412570 TI - Patient-level predictors of achieving early glycaemic control in Type 2 diabetes mellitus: a population-based study. AB - AIMS: To identify individual predictors of early glycaemic control in people with Type 2 diabetes mellitus after initiation of first glucose-lowering drug treatment in everyday clinical practice. METHODS: Using medical registries, we identified a population-based cohort of people with a first-time glucose-lowering drug prescription in Northern Denmark in the period 2000-2012. We used Poisson regression analysis to examine patient-level predictors of success in reaching early glycaemic control [HbA1c target of < 53 mmol/mol (7%)] < 6 months after treatment start. RESULTS: Among the 38 418 people (median age 63 years), 27 545 (72%) achieved early glycaemic control. The strongest predictor of achieving early control was pre-treatment HbA1c level; compared with a pre-treatment HbA1c level of <= 58 mmol/mol (7.5%), the adjusted relative risks of attaining early control were 0.63 (95% CI 0.61-0.64) for baseline HbA1c levels of > 58 and <= 75 mmol/mol (> 7.5 and <= 9%), and 0.58 (95% CI 0.57-0.59) for a baseline HbA1c level of > 9% (> 75 mmol/mol). All other examined predictors were only weakly associated with the chance of achieving early control. After adjustment, the only characteristics that remained independently associated with early control (in addition to high baseline HbA1c ) were being widowed (adjusted relative risk 0.95; 95% CI 0.93-0.97) and having a high Charlson comorbidity index score (score >= 3; adjusted relative risk 0.94; 95% CI 0.90-0.97). CONCLUSIONS: In a real world clinical setting, people with Type 2 diabetes mellitus initiating glucose lowering medication had a similar likelihood of achieving glycaemic control, regardless of sex, age, comorbidities and other individual factors; the only strong and potentially modifiable predictor was HbA1c before therapy start. PMID- 27412571 TI - Tuning of Supramolecular Architectures of l-Valine-Containing Dicyanoplatinum(II) 2,2'-Bipyridine Complexes by Metal-Metal, pi-pi Stacking, and Hydrogen-Bonding Interactions. AB - A series of newly synthesized dicyanoplatinum(II) 2,2'-bipyridine complexes exhibits self-assembly properties in solution after the incorporation of the l valine amino units appended with various hydrophobic motifs. These l-valine derived substituents were found to have critical control over the aggregation behaviors of the complexes in the solution state. On one hand, one of the complexes was found to exhibit interesting circularly polarized luminescence (CPL) signals at low temperature due to the formation of chiral spherical aggregates in the temperature-dependent studies. On the other hand, systematic transformation from less uniform aggregates to well-defined fibrous and rod-like structures via Pt???Pt and pi-pi stacking interactions has also been observed in the mixed-solvent studies. These changes were monitored by UV/Vis absorption, emission, circular dichroism (CD), and CPL spectroscopies, and morphologies were studied by electron microscopy. PMID- 27412574 TI - Ironing out iron deficiency in heart failure. PMID- 27412572 TI - The emerging roles of Jab1/CSN5 in cancer. AB - C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an evolutionarily conserved and multifunctional protein that involves in controlling cellular proliferation and apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage and repair. The CSN is a highly conservative protein from yeast to human and interacts with the cullin RING family of ubiquitin ligases so that it could be execute a process of removing NEDD8, a ubiquitin-like polypeptide (deneddylase activity). The role of Jab1/CSN5's multi-function has been proved as being oncogenic in nature, what is more, Jab1/CSN5 has been confirmed by much evidence that it participates in the carcinogenesis progression and is tightly associated with poor prognosis. However, the biologic implication of Jab1/CSN5 activity during the cancer's development is unclear. We performed a systematic literature review and assessment from PubMed and Medline databases in this article. Jab1/CSN5 is participate in a lot of biologic responses, including cell proliferation, apoptosis, cell cycle regulation, DNA metabolism, invasion, DNA damage and repair, and recurrence. It also promotes cell transformation and tumorigenesis. In this review, we mainly expound the progress in the function and research advances of Jab1/CSN5 and in untangling the Jab1/CSN5 signaling pathway. Based on these bases, its potential as a therapeutic target for cancer can play a greater role in future cancer treatment. PMID- 27412573 TI - Dietary patterns and risk of colorectal adenoma: a systematic review and meta analysis of observational studies. AB - BACKGROUND: Current evidence suggests that dietary patterns may play an important role in colorectal cancer risk. The present study aimed to perform a systematic review and meta-analysis of observational studies exploring the association between dietary patterns and colorectal adenomas (a precancerous condition). METHODS: Pubmed and EMBASE electronic databases were systematically searched to retrieve eligible studies. Only studies exploring the risk or association with colorectal adenomas for the highest versus lowest category of exposure to a posteriori dietary patterns were included in the quantitative analysis. Random effects models were applied to calculate relative risks (RRs) of colorectal adenomas for high adherence to healthy or unhealthy dietary patterns. Statistical heterogeneity and publication bias were explored. RESULTS: Twelve studies were reviewed. Three studies explored a priori dietary patterns using scores identifying adherence to the Mediterranean, Paleolithic and Dietary Approaches to Stop Hypertension (DASH) diet and reported an association with decreased colorectal adenoma risk. Two studies tested the association with colorectal adenomas between a posteriori dietary patterns showing lower odds of disease related to plant-based compared to meat-based dietary patterns. Seven studies identified 23 a posteriori dietary patterns and the analysis revealed that higher adherence to healthy and unhealthy dietary patterns was significantly associated risk of colorectal adenomas (RR = 0.81, 95% confidence interval = 0.71, 0.94 and RR = 1.24, 95% confidence interval = 1.13, 1.35, respectively) with no evidence of heterogeneity or publication bias. CONCLUSIONS: The results of this systematic review and meta-analysis indicate that dietary patterns may be associated with the risk of colorectal adenomas. PMID- 27412575 TI - An Empyema within a Hematoma: An Unexpected Complication of a Subdural Hematoma in an Elderly Adult. PMID- 27412576 TI - Nanotechnology is like ... The rhetorical roles of analogies in public engagement. AB - Lay people are increasingly invited to deliberate on emerging technologies in public engagement settings. Analogies appear frequently in these contexts and are commonly understood as means of making sense of and forming an opinion on emerging technologies. This article provides an alternative perspective, which conceptualizes analogies as rhetorical devices employed to achieve specific functions. A repertoire of rhetorical roles is traced in four public engagement settings on nanotechnology: (1) analogies suggesting acceptance/rejection of specific nano-applications, (2) anticipatory and alerting analogies constructed to plausibilize and prevent futures, (3) killer analogies closing debate and arguments, and (4) "nano is not like nano" moves that distinguish between application domains. Each role points to specific dimensions and tensions of public engagement processes. Overall, the findings reveal that lay people use analogies to make arguments and enforce framings rather than to just make sense of nanotechnology, which refutes the assumption of a public opinion deficit. PMID- 27412577 TI - [Health Campaigns Against Malaria in Spain through the Specialized Journalism in Spain (1929-1954)]. AB - BACKGROUND: Malaria was one of the most important public health problems of the Colonial Medicine and, for this reason, the subject was reflected in the Spanish medical journalism. The aim of the paper was to reconstruct the Spanish contributions to international health during the first half of the twentieth century. METHODS: The primary sources of information on malaria were the medical journals Medicina de los Paises Calidos and Medicina Colonial, between 1929 and 1954. The documents were classified according to the sections of the magazine and its contents were studied, framing them in the history of international public health. RESULTS: In primary sources were found 466 documents. Malaria was one of the major diseases of the Spanish Protectorate in Morocco and Spanish Guinea, favoured by the occupation of the Spanish army. Antimalaria campaigns included strategies such as the use of Dichloro-diphenyl-trichloroethane, preventive education and massive quininizacion. Malariology in the specialized journalism, experienced a growing boom. The most outstanding authors in magazines analyzed were Gustavo Pittaluga, Sadi de Buen, Eliseo de Buen and Juan Gil-Collado. CONCLUSIONS: The Spanish specialized journalism provides the importance e interaction in antimalaria campaigns in Spain and Spanish African colonies of scientific, professional, political and military factors. The colonial situation was negative and marked differences between metropolis and colonies in terms of the effort, efficiency and the different temporal sequence of the measures undertaken. PMID- 27412578 TI - The aflatoxin M1 crisis in the Serbian dairy sector: the year after. AB - During the last 3 years, high aflatoxin M1 (AFM1) concentrations in milk and dairy products occurred in Serbia. It resulted in periodical change of the official regulations regarding maximum levels (MLs) of AFM1 as set by the Serbian Government. The aim of this study was to compare the occurrence of AFM1 in raw milk and dairy products during 2015 and also to determine whether there were some differences in AFM1 level among seasons. The AFM1 level exceeded the European Union ML in 29.3% of raw milk and 4.2% of milk product samples. The highest level of AFM1 in raw milk was found during the autumn season, while during the rest of the 2015, it was significantly lower. Although the improvement of dairy products safety was evident in 2015 when compared to 2013 and 2014, the cause of high concentrations in raw milk remained unresolved yet. This study indicates that dairy plants introduced control measures and refused reception of too high contaminated raw milk. PMID- 27412579 TI - A Meta-Analytic Review of the Efficacy of Physical Exercise Interventions on Cognition in Individuals with Autism Spectrum Disorder and ADHD. AB - This review evaluates the efficacy of using physical exercise interventions on improving cognitive functions in individuals with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD). This review includes a meta-analysis based on a random-effects model of data reported in 22 studies with 579 participants aged 3-25 year old. The results revealed an overall small to medium effect of exercise on cognition, supporting the efficacy of exercise interventions in enhancing certain aspects of cognitive performance in individuals with ASD and/or ADHD. Specifically, similar to the general population literature, the cognitive benefits of exercise are not consistent across all aspects of cognitive functions (i.e., some areas are not improved). The clinical significance of the reported effect sizes is also considered. PMID- 27412580 TI - Prognostic relevance of circulating endothelial progenitor cells in patients with chronic heart failure. AB - Novel strategies for a tailored risk prediction in chronic heart failure (CHF) are crucial to identify patients at very high risk for an improved patient management and to specify treatment regimens. Endothelial progenitor cells (EPCs) are an important endogenous repair mechanism with the ability to counteract endothelial injury and the possibility of new vessel formation. We hypothesised that exhaustion of circulating EPCs may be a suitable prognostic biomarker in patients with CHF. EPCs, defined as CD34+CD45dimKDR+ cells, were analysed using fluorescence-activated cell sorting. EPCs were measured in 185 patients with CHF including 87 (47 %) patients with ischaemic aetiology and 98 (53 %) patients with non-ischaemic CHF and followed for a median time of 2.7 years. During this period, 34.7 % of patients experienced the primary study endpoint all-cause mortality. EPC count was a significant and independent inverse predictor of mortality with an hazard ratio hazard ratio (HR) per increase of one standard deviation (1-SD) of 0.47 (95 % confidence interval [CI]: 0.35-0.61; p<0.001) and remained significant after multivariable adjustment for a comprehensive set of cardiovascular risk factors and potential confounders with a HR per 1-SD of 0.54 (95 % CI: 0.4-0.73; p<0.001). EPCs further demonstrated additional prognostic information indicated by improvements in C-statistic, net reclassification index and integrated discrimination increment. In conclusion, in our study circulating EPCs turned out as strong and independent inverse predictors of mortality underlining the importance of an impaired endothelial repair mechanism in the pathophysiology and progression of CHF. PMID- 27412581 TI - Inhibition of the Injectisome and Flagellar Type III Secretion Systems by INP1855 Impairs Pseudomonas aeruginosa Pathogenicity and Inflammasome Activation. AB - With the rise of multidrug resistance, Pseudomonas aeruginosa infections require alternative therapeutics. The injectisome (iT3SS) and flagellar (fT3SS) type III secretion systems are 2 virulence factors associated with poor clinical outcomes. iT3SS translocates toxins, rod, needle, or regulator proteins, and flagellin into the host cell cytoplasm and causes cytotoxicity and NLRC4-dependent inflammasome activation, which induces interleukin 1beta (IL-1beta) release and reduces interleukin 17 (IL-17) production and bacterial clearance. fT3SS ensures bacterial motility, attachment to the host cells, and triggers inflammation. INP1855 is an iT3SS inhibitor identified by in vitro screening, using Yersinia pseudotuberculosis Using a mouse model of P. aeruginosa pulmonary infection, we show that INP1855 improves survival after infection with an iT3SS-positive strain, reduces bacterial pathogenicity and dissemination and IL-1beta secretion, and increases IL-17 secretion. INP1855 also modified the cytokine balance in mice infected with an iT3SS-negative, fT3SS-positive strain. In vitro, INP1855 impaired iT3SS and fT3SS functionality, as evidenced by a reduction in secretory activity and flagellar motility and an increase in adenosine triphosphate levels. As a result, INP1855 decreased cytotoxicity mediated by toxins and by inflammasome activation induced by both laboratory strains and clinical isolates. We conclude that INP1855 acts by dual inhibition of iT3SS and fT3SS and represents a promising therapeutic approach. PMID- 27412582 TI - The Bacterial Stress-Responsive Hsp90 Chaperone (HtpG) Is Required for the Production of the Genotoxin Colibactin and the Siderophore Yersiniabactin in Escherichia coli. AB - The genotoxin colibactin, synthesized by Escherichia coli, is a secondary metabolite belonging to the chemical family of hybrid polyketide/nonribosomal peptide compounds. It is produced by a complex biosynthetic assembly line encoded by the pks pathogenicity island. The presence of this large cluster of genes in the E. coli genome is invariably associated with the high-pathogenicity island, encoding the siderophore yersiniabactin, which belongs to the same chemical family as colibactin. The E. coli heat shock protein HtpG (Hsp90Ec) is the bacterial homolog of the eukaryotic molecular chaperone Hsp90, which is involved in the protection of cellular proteins against a variety of environmental stresses. In contrast to eukaryotic Hsp90, the functions and client proteins of Hsp90Ec are poorly known. Here, we demonstrated that production of colibactin and yersiniabactin is abolished in the absence of Hsp90Ec We further characterized an interplay between the Hsp90Ec molecular chaperone and the ClpQ protease involved in colibactin and yersiniabactin synthesis. Finally, we demonstrated that Hsp90Ec is required for the full in vivo virulence of extraintestinal pathogenic E. coli This is the first report highlighting the role of heat shock protein Hps90Ec in the production of two secondary metabolites involved in E. coli virulence. PMID- 27412583 TI - Bioluminescent Probe for Detecting Mercury(II) in Living Mice. AB - A novel bioluminescence probe for mercury(II) was obtained on the basis of the distinct deprotection reaction of dithioacetal to decanal, so as to display suitable sensitivity and selectivity toward mercury(II) over other ions with bacterial bioluminescence signal. These experimental results indicated such a probe was a novel promising method for mercury(II) bioluminescence imaging in environmental and life sciences ex vivo and in vivo. PMID- 27412585 TI - Erratum to: RNA sequencing reveals a depletion of collagen targeting microRNAs in Dupuytren's disease. PMID- 27412584 TI - [A 10-year evaluation of geriatric rehabilitation in Rhineland-Palatinate]. AB - BACKGROUND: An evaluation of geriatric rehabilitation has been carried out in Rhineland-Palatinate for over 10 years by collecting data of patients absolving an inpatient geriatric rehabilitation program. The aim of the project was to improve the transparency of outcome quality. The procedure is equally supported by geriatric rehabilitation clinics, health insurance companies and the Medical Service of Health Insurance (MDK). MATERIAL AND METHODS: Consented information about the rehabilitation process has been collected from every geriatric rehabilitation clinic in Rhineland-Palatinate. The data were pseudonymized and sent to the MDK in Rhineland-Palatinate for statistical analysis. The dataset included age, diagnosis, life circumstances before rehabilitation, duration of the rehabilitation, therapy implemented and need for support (with or without personal assistance) in eight activities of daily living at the beginning and at the end of rehabilitation. RESULTS: The results of 45,751 participants who underwent rehabilitation between 2005 and 2014 are presented. There was a slight tendency towards an increase in the number of very old geriatric patients undergoing rehabilitation. The average duration of rehabilitation decreased slightly during the observation period, while the frequency of therapy increased. The reduction in the need for assistance during rehabilitation remained constant over the observation period. CONCLUSION: Systematic evaluation improves the transparency of the rehabilitation process. PMID- 27412586 TI - Individual cell heterogeneity in Predictive Food Microbiology: Challenges in predicting a "noisy" world. AB - Gene expression is a fundamentally noisy process giving rise to a significant cell to cell variability at the phenotype level. The phenotypic noise is manifested in a wide range of microbial traits. Heterogeneous behavior of individual cells is observed at the growth, survival and inactivation responses and should be taken into account in the context of Predictive Food Microbiology (PMF). Recent methodological advances can be employed for the study and modeling of single cell dynamics leading to a new generation of mechanistic models which can provide insight into the link between phenotype, gene-expression, protein and metabolic functional units at the single cell level. Such models however, need to deal with an enormous amount of interactions and processes that influence each other, forming an extremely complex system. In this review paper, we discuss the importance of noise and present the future challenges in predicting the "noisy" microbial responses in foods. PMID- 27412587 TI - Application of a physiologically based pharmacokinetic model for the evaluation of single-point plasma phenotyping method of CYP2D6. AB - PURPOSE: Determining metabolic ratio from single-point plasma is potentially a good phenotyping method of CYP2D6 to reduce the required time interval and increase the reliability of data. It is difficult to conduct large sample size clinical trials to evaluate this phenotyping method for multiple plasma points. A physiologically based pharmacokinetic (PBPK) model can be developed to do simulations based on the large virtual Chinese population and evaluate single point plasma phenotyping method of CYP2D6. METHODS: Pharmacokinetic data of dextromethorphan (DM) and its metabolite dextrorphan (DX) after oral administration were used for model development. The SimCYP(r) model incorporating Chinese demographic, physiological, and enzyme data was used to simulate DM and DX pharmacokinetics in different phenotype groups. RESULTS: The ratios of the simulated to the observed mean AUC and Cmax of DM were 1.01 and 0.81 for extensive metabolizers (EMs), 0.90 and 0.81 for intermediate metabolizers (IMs), and 1.12 and 0.84 for poor metabolizers (PMs). The ratios of the simulated to the observed mean AUC and Cmax of DX were 1.12 and 0.89 for EMs, 0.66 and 0.62 for IMs. All ratios were within the predefined criterion of 0.5-2. The simulations of DM and DX pharmacokinetic profiles in 1000 virtual Chinese subjects with reported frequencies of different phenotypes indicated that statistically significant correlations were found between metabolic ratio of DM to DX (MRDM/DX) from AUC and from single-point plasma from 1 to 30h (all p-values <0.001). CONCLUSION: MRDM/DX from single-point plasma from 1 to 30h after the administration of 30mg controlled-release DM could predict the MRDM/DX from AUC well and could be used as the phenotyping method of CYP2D6 for EMs, IMs, and PMs. PMID- 27412588 TI - Effect of electroacupuncture stimulation on expression of angiotensinogen, angiotensin II type 1 receptor, endothelin-1, and endothelin a receptor mRNA in spontaneously hypertensive rat aorta. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation on the expressions of angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), endothelin-1 (ET1), and endothelin A receptor (ETAR) mRNA in spontaneously hypertensive rat (SHR) aorta. METHODS: Eighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui (DU 20) and Zusanli (ST 36) acupoint (SHR-AP) group, and an SHR non-acupoint (SHR-NAP) group, with 6 rats in each group. Six Wistar rats were used as a control. Rats in the SHR-AP group were stimulated by DU 20 and ST 36 acupoints, both of which were connected with EA. EA was handled one time every Monday, Wednesday and Friday, for total 24 times (8 weeks). SHRNAP rats were acupointed at a 15 degrees angle flat into 0.5 cm to two points, which were 1 and 2 cm from rail tip separately. EA parameters were the same as the SHR-AP rats. SHR control rats and Wistar rats were fixed without EA. Real-time quantitative polymerase chain reaction (PCR) was used to measure AGT, AT1R, ET1, and ETAR mRNA expression in rat aorta. RESULTS: EA stimulation significantly reduced rat aorta vascular AGT, ET1, ETAR and AT1R mRNA expressions in the SHR-AP and SHR-NAP groups (P <0.01). Among these four genes, AT1R mRNA expression was significantly lower in the SHR-AP than in the SHR-NAP group (P <0.01). CONCLUSION: EA could reduce the AT1R mRNA expression in SHR-AP rat aorta, indicating a potential mechanism for the hypotensive effects of EA. PMID- 27412589 TI - Allicin improves cardiac function by protecting against apoptosis in rat model of myocardial infarction. AB - OBJECTIVE: To study the effects of allicin on cardiac function and underlying mechanism in rat model of myocardial infarction (MI). METHODS: Ninety-four Wistar rats were randomly assigned to 6 groups (n=14-16 per group): sham control group [underwent thoracotomy without left anterior descending (LAD) occlusion and only received an injection of the same amount of citrate buffer], MI control group (subjected to LAD occlusion and only received an injection of same amount of citrate buffer), positive control group (subjected to LAD occlusion and received an injection of diltiazem hydrochloride at the dose of 1.5 mg/kg), and MI + allicin groups (subjected to LAD occlusion and received an injection of allicin at the doses of 1.2, 1.8, and 3.6 mg/kg). All of the drugs were administered intraperitoneally daily for 21 days. The infarct area was measured by myocardial staining. Hematoxylin-eosin staining was used to observe the pathological changes. Cardiac function parameters were assessed by echocardiography. The myocardial apoptotic index was estimated by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining. The expression of Bax and Bcl-2 were detected by quantificational real-time polymerase chain reaction and Western blot. RESULTS: Treatment with allicin could attenuate the myocardial infarct area (P<0.05) and relieve the changes of the myocardium. The left ventricular anterior wall diastolic and systolic thicknesses were increased in the allicin-treated groups (P<0.05), while there was no signifificant difference in the left ventricular posterior wall diastolic and systolic thickness (P>0.05). The left ventricular internal diameter in systole, ejection fraction, fractional shortening, and stroke volume were dramatically elevated in allicin-treated rats (P<0.05). Allicin dose-dependently reduced creatine kinase and lactate dehydrogenase levels (P<0.05). The myocardial apoptotic index was also markedly lowered, and Bax expression was signifificantly decreased, whereas Bcl-2 expression exhibited an opposite trend in allicin-treated rats (P<0.05). CONCLUSION: Allicin appears to exert a cardioprotective effect that may be linked to blocking Bcl-2/Bax signaling pathway-denpendent apoptosis, further improving cardiac function. PMID- 27412590 TI - Bromelain and cardiovascular risk factors in diabetes: An exploratory randomized, placebo controlled, double blind clinical trial. AB - OBJECTIVE: To assess whether the dietary supplement (bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease (CVD) risk factors in patients with diabetes. METHODS: This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1,050 mg/day) on plasma fibrinogen. This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years (standard deviation (SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg (3*350 mg) of either bromelain or starch-filled placebo capsules, two to be taken (2*350 mg) after breakfast and another (350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks. RESULTS: The change in the fibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L (standard deviation (SD) 0.86g/L) compared with the mean reduction of 0.36 g/L (SD 0.96 g/L) for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22 g/L), =0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study. CONCLUSION: This RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain. PMID- 27412591 TI - Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection. AB - Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5alpha restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4(+) T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel "bar-coded" challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda. IMPORTANCE: Nonhuman primate research has relied on only a few infectious molecular clones for a myriad of diverse research projects, including pathogenesis, preclinical vaccine evaluations, transmission, and host-versus pathogen interactions. With new data suggesting a selected phenotype of the virus that causes infection (i.e., the transmitted/founder virus), we sought to generate and characterize infectious molecular clones from two widely used simian immunodeficiency virus lineages (SIVmac251 and SIVsmE660). Although the exact requirements necessary to be a T/F virus are not yet fully understood, we generated cloned viruses with all the necessary characteristic of a successful T/F virus. The cloned viruses revealed typical acute and set point viral-load dynamics with pathological immune activation, lymphoid tissue damage progressing to significant immunodeficiency, and AIDS-defining clinical endpoints in some animals. These T/F clones represent a new molecular platform for studies requiring authentic T/F viruses. PMID- 27412592 TI - Single-Site Glycoprotein Mutants Inhibit a Late Event in Sindbis Virus Assembly. AB - A panel of Sindbis virus mutants that were suspected to have deficiencies in one or more aspects of their replication cycles was examined in baby hamster kidney (BHK) cells. These included an amino acid deletion (DeltaH230) and substitution (H230A) in the Sindbis glycoprotein E1_H230 and similar mutants in E2_G209 (G209A, G209D, and DeltaG209). Neither H230 mutation produced a measurable titer, but repeated passaging of the H230A mutant in BHK cells produced a second-site compensatory mutant (V231I) that partially rescued both H230 mutants. Electron micrograph (EM) images of these mutants showed assembled viral nucleocapsids but no completed, mature virions. EM of the compensatory mutant strains showed complete virus particles, but these now formed paracrystalline arrays. None of the E2_G209 substitution mutants had any effect on virus production; however, the deletion mutant (DeltaG209) showed a very low titer when grown at 37 degrees C and no titer when grown at 28 degrees C. When the deletion mutant grown at 28 degrees C was examined by EM, partially budded virions were observed at the cell surface. (35)S labeling of this mutant confirmed the presence of mutant virus protein in the transfected BHK cell lysate. We conclude that H230 is essential for the assembly of complete infectious Sindbis virus virions and that the presence of an amino acid at E2 position 209 is required for complete budding of Sindbis virus particles although several different amino acids can be at this location without affecting the titer. IMPORTANCE: Our data show the importance of single-site mutations at E1_H230 and E2_G209 in Sindbis virus glycoproteins. These sites have been shown to affect assembly and antibody binding in previous studies. Our data indicate that mutation of one histidine residue in E1 is detrimental to the assembly of Sindbis virus particles in baby hamster kidney cells. Repeated passaging leads to a second-site substitution that partially restores the titer although EM still shows an altered phenotype. Substitutions at position G209 in E2 have no effect on titer, but deletion of this residue greatly reduces titer and again prevents assembly. When this mutant is grown at a lower temperature, virus particles bud from the host cell, but budding arrests before the progeny virus escapes. These results allow us to conclude that these sites have essential roles in assembly, and E2_G209 shows us a new viral egress phenotype. PMID- 27412593 TI - Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance. AB - RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3D(pol), as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3D(pol) may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3D(pol)-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3D(pol) decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3D(pol) increased the frequency of recombination. The 3D(pol) Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G->A and C->U mutations in viral RNA. We conclude that 3D(pol) Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance. IMPORTANCE: Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a polymerase mutation that disables recombination renders the virus more susceptible to the antiviral drug ribavirin, suggesting that recombination contributes to ribavirin resistance. Elucidating the molecular mechanisms of RNA replication and recombination may help mankind achieve and maintain poliovirus eradication. PMID- 27412595 TI - Human Papillomavirus Entry: Hiding in a Bubble. AB - Incoming human papillomavirus (HPV) utilize vesicular transport to traffic from the plasma membrane to the trans-Golgi network. Following nuclear envelope breakdown during mitosis, the viral DNA associates with condensed chromosomes utilizing spindle microtubules for delivery. Most intriguingly, the viral DNA resides in a transport vesicle until mitosis is completed and the nuclear envelope has reformed. This finding provides support for the transient existence of nuclear membrane-bound vesicles. Due to their transient nature, it also points to the existence of a cell pathway for the disposal of vesicles ending up fortuitously or purposefully in the nucleus. PMID- 27412594 TI - Myristoylation of the Arenavirus Envelope Glycoprotein Stable Signal Peptide Is Critical for Membrane Fusion but Dispensable for Virion Morphogenesis. AB - Arenaviruses are responsible for severe and often fatal hemorrhagic disease. In the absence of effective antiviral therapies and vaccines, these viruses pose serious threats to public health and biodefense. Arenaviruses enter the host cell by fusion of the viral and endosomal membranes, a process mediated by the virus envelope glycoprotein GPC. Unlike other class I viral fusion proteins, GPC retains its stable signal peptide (SSP) as an essential third subunit in the mature complex. SSP spans the membrane twice and is myristoylated at its cytoplasmic N terminus. Mutations that abolish SSP myristoylation have been shown to reduce pH-induced cell-cell fusion activity of ectopically expressed GPC to ~20% of wild-type levels. In order to examine the role of SSP myristoylation in the context of the intact virus, we used reverse genetics to generate Junin viruses (Candid #1 isolate) in which the critical glycine-2 residue in SSP was either replaced by alanine (G2A) or deleted (DeltaG2). These mutant viruses produced smaller foci of infection in Vero cells and showed an ~5-fold reduction in specific infectivity, commensurate with the defect in cell-cell fusion. However, virus assembly and GPC incorporation into budded virions were unaffected. Our findings suggest that the myristate moiety is cryptically disposed in the prefusion GPC complex and may function late in the fusion process to promote merging of the viral and cellular membranes. IMPORTANCE: Hemorrhagic fever arenaviruses pose significant threats to public health and biodefense. Arenavirus entry into the host cell is promoted by the virus envelope glycoprotein GPC. Unlike other viral envelope glycoproteins, GPC contains a myristoylated stable signal peptide (SSP) as an essential third subunit. Myristoylation has been shown to be important for the membrane fusion activity of recombinantly expressed GPC. Here, we use reverse genetics to study the role of SSP myristoylation in the context of the intact virion. We find that nonmyristoylated GPC mutants of the Candid #1 strain of Junin virus display a commensurate deficiency in their infectivity, albeit without additional defects in virion assembly and budding. These results suggest that SSP myristoylation may function late in the fusion process to facilitate merging of the viral and cellular membranes. Antiviral agents that target this novel aspect of GPC membrane fusion may be useful in the treatment of arenavirus hemorrhagic fevers. PMID- 27412596 TI - Human Papillomavirus E2 Protein: Linking Replication, Transcription, and RNA Processing. AB - The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelium. This means that viral proteins must exert control over epithelial gene expression in order to optimize viral production. The HPV E2 protein controls replication, transcription, and viral genome partitioning during the viral infectious life cycle. It consists of a nucleic acid-binding domain and a protein-protein interaction domain separated by a flexible serine and arginine rich hinge region. Over the last few years, mounting evidence has uncovered an important new role for E2 in viral and cellular RNA processing. This Gem discusses the role of E2 in controlling the epithelial cellular environment and how E2 might act to coordinate late events in the viral replication cycle. PMID- 27412597 TI - Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species. AB - The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 A for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another. IMPORTANCE: Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species. PMID- 27412598 TI - High-Throughput Small Interfering RNA Screening Identifies Phosphatidylinositol 3 Kinase Class II Alpha as Important for Production of Human Cytomegalovirus Virions. AB - High-throughput small interfering RNA (siRNA) screening is a useful methodology to identify cellular factors required for virus replication. Here we utilized a high-throughput siRNA screen based on detection of a viral antigen by microscopy to interrogate cellular protein kinases and phosphatases for their importance during human cytomegalovirus (HCMV) replication and identified the class II phosphatidylinositol 3-kinase class II alpha (PI3K-C2A) as being involved in HCMV replication. Confirming this observation, infected cells treated with either pooled or individual siRNAs targeting PI3K-C2A mRNA produced approximately 10 fold less infectious virus than the controls. Western blotting and quantitative PCR analysis of infected cells treated with siRNAs indicated that depletion of PI3K-C2A slightly reduced the accumulation of late but not immediate early or early viral antigens and had no appreciable effect on viral DNA synthesis. Analysis of siRNA-treated cells by electron microscopy and Western blotting indicated that PI3K-C2A was not required for the production of viral capsids but did lead to increased numbers of enveloped capsids in the cytoplasm that had undergone secondary envelopment and a reduction in the amount of viral particles exiting the cell. Therefore, PI3K-C2A is a factor important for HCMV replication and has a role in the production of HCMV virions. IMPORTANCE: There is limited information about the cellular factors required for human cytomegalovirus (HCMV) replication. Therefore, to identify proteins involved in HCMV replication, we developed a methodology to conduct a high-throughput siRNA screen of HCMV infected cells. From our screening data, we focused our studies on the top hit from our screen, the lipid kinase phosphatidylinositol 3-kinase class II alpha (PI3K-C2A), as its role in HCMV replication was unknown. Interestingly, we found that PI3K-C2A is important for the production of HCMV virions and is involved in virion production after secondary envelopment of viral capsids, the encapsidation of HCMV capsids by a lipid bilayer that occurs before virions exit the cell. PMID- 27412599 TI - Relative Contributions of Herpes Simplex Virus 1 ICP0 and vhs to Loss of Cellular IFI16 Vary in Different Human Cell Types. AB - The herpes simplex virus 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase that promotes the degradation of several host cell proteins. Most studies have found that ICP0 promotes the loss of IFI16 in infected cells, but one study reported that ICP0 was not necessary or sufficient for loss of IFI16 in a tumor-derived cell line. Therefore, in this study, we examined the requirement for ICP0 in promoting the loss of IFI16 in several normal and tumor-derived cell lines. HSV-1 infection resulted in an observable decrease of IFI16 protein levels in normal human foreskin fibroblasts (HFFs), normal oral keratinocytes (NOKs), and HeLa cells but not in U2OS cells. During infection with an ICP0-null virus, we observed a reduced loss of IFI16 in HFFs and NOKs but not in HeLa cells. Ectopic expression of ICP0 from a transfected plasmid was sufficient to promote the loss of IFI16 in HFFs and NOKs. In the absence of ICP0, we observed a delayed reduction of IFI16 protein that correlated with a reduction in the steady-state levels of IFI16 mRNA. In addition, we show that the ICP0-independent loss of IFI16 in HeLa cells is dependent in part on the activity of the viral virion host shutoff (vhs) tegument protein. Together, these results demonstrate that HSV-1 promotes the loss of IFI16 through at least two mechanisms: (i) by ICP0-dependent degradation of IFI16 and (ii) by vhs-dependent turnover of IFI16 mRNA. In addition, this study highlights a potential intrinsic difference between normal and tumor-derived cells for the activities of IFI16 and HSV-1 ICP0. IMPORTANCE: HSV-1 is a ubiquitous virus that establishes a lifetime persistent infection in humans. The relative success of HSV-1 as a pathogen is, in part, dependent on the expression of viral proteins that counteract host intrinsic defense mechanisms and that modulate immune responses during viral infection. In this study, we examined the relative roles of two viral gene products for the ability to promote loss of the antiviral IFI16 DNA sensor. We demonstrate that the viral immediate early ICP0 protein plays a dominant role in the loss of IFI16 in normal, but not tumor-derived, human cell lines. In contrast, viral vhs-mediated loss of IFI16 by mRNA destabilization is revealed to be dominant in tumor-derived cells in which ICP0 is nonfunctional. Together, these results contribute to our understanding of how HSV-1 modulates IFI16 protein levels and highlight cell-type-dependent differences between normal and tumor-derived cells. PMID- 27412600 TI - Identification of a New Benzimidazole Derivative as an Antiviral against Hepatitis C Virus. AB - Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them. Of these, we selected a compound (B5) that is currently ending clinical phase I evaluation for neurodegenerative diseases. In hepatoma cells, B5 inhibited HCV infection in a pangenotypic and dose-dependent manner, and its antiviral activity was confirmed in primary hepatocytes. B5 also inhibited infection by pseudoparticles expressing HCV envelope glycoproteins E1 and E2, and we demonstrated that it affects a postattachment stage of the entry step. Virus with resistance to B5 was selected by sequential passage in the presence of the drug, and reverse genetics experiments indicated that resistance was conferred mainly by a single mutation in the putative fusion peptide of E1 envelope glycoprotein (F291I). Furthermore, analyses of the effects of other closely related compounds on the B5-resistant mutant suggest that B5 shares a mode of action with other 4-aminoquinoline-based molecules. Finally, mice with humanized liver that were treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle. IMPORTANCE: In the last 4 years, HCV therapy has been profoundly improved with the approval of direct-acting antivirals in clinical practice. Nevertheless, the high costs of these drugs limit access to therapy in most countries. The present study reports the identification and characterization of a compound (B5) that inhibits HCV propagation in cell culture and is currently ending clinical phase I evaluation for neurodegenerative diseases. This molecule inhibits the HCV life cycle by blocking virus entry. Interestingly, after selection of drug-resistant virus, a resistance mutation in the putative fusion peptide of E1 envelope glycoprotein was identified, indicating that B5 could be used to further investigate the fusion mechanism. Furthermore, mice with humanized liver treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle. PMID- 27412601 TI - Mitteilungen der DGKFO. PMID- 27412603 TI - Parasites in Rheumatoid Arthritis: Imminent Threat or Protective Effect? AB - Parasitic infections are among the oldest and most common infections in humans. Host defense alterations caused by autoimmune diseases or immunosuppressive drugs can cause modifications of the symptoms: indolent parasites can be reactivated, asymptomatic patients may experience new symptoms, or mild or moderate symptoms can become serious and, rarely, may lead to death. In recent years, new drugs have been used in the treatment of rheumatoid arthritis (RA), causing a greater level of immunosuppression and, therefore, more concerns regarding the risk of serious parasitic diseases. Of note, experimental studies have demonstrated that the immunomodulation induced by infection with helminths can minimize the occurrence and severity of rheumatoid arthritis. Products derived from helminths (such as glycoprotein ES-62) can exert favorable effects in RA patients via their anti-inflammatory actions. Greater knowledge of these substances may serve as a basis for the development of new treatments for RA. The full impact of parasitic diseases on patients with rheumatoid arthritis remains controversial, and further studies are warrented. PMID- 27412604 TI - Roseomonas arcticisoli sp. nov., isolated from Arctic tundra soil. AB - A pale pink, Gram-reaction-negative, non-motile, aerobic bacterium, designated MC 3624T, was isolated from a tundra soil near Ny-Alesund, Svalbard Archipelago, Norway (78 degrees N). Growth occurred at 10-37 degrees C (optimum 25-30 degrees C) and at pH 6.0-9.0 (optimum pH 8.0). The predominant fatty acids were C16 : 0 (17.7 %), C18 : 1omega7c 11-methyl (13.4 %), summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) (10.1 %) and summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c) (38.3 %). The major respiratory quinone was ubiquinone-10, and the main polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and an unidentified aminolipids. The DNA G+C content was 68.9 mol%. Carotenoids of the spirilloxanthin series were produced. The nearest neighbour to the novel strain was Roseomonas wooponensis WW53T (94.36 % 16S rRNA gene sequence similarity). On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain MC 3624T represents a novel species of the genus Roseomonas, for which the name Roseomonas arcticisoli sp. nov. is proposed. The type strain is MC 3624T (=CCTCC AB 2014278T=LMG 28637T). PMID- 27412602 TI - Update on Pathogenesis of Sjogren's Syndrome. AB - Sjogren's syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjogren's syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis - the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of the innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms. Role of epigenetic and environmental role factors is also being explored. SS has also some unique features such as congenital heart block and high incidence of lymphoma; disease mechanisms accounting for these manifestations are also reviewed. PMID- 27412605 TI - Core-shell self-assembly triggered via a thiol-disulfide exchange reaction for reduced glutathione detection and single cells monitoring. AB - A novel core-shell DNA self-assembly catalyzed by thiol-disulfide exchange reactions was proposed, which could realize GSH-initiated hybridization chain reaction (HCR) for signal amplification and molecules gathering. Significantly, these self-assembled products via electrostatic interaction could accumulate into prominent and clustered fluorescence-bright spots in single cancer cells for reduced glutathione monitoring, which will effectively drive cell monitoring into a new era. PMID- 27412606 TI - Conserved Noncoding Elements in the Most Distant Genera of Cephalochordates: The Goldilocks Principle. AB - Cephalochordates, the sister group of vertebrates + tunicates, are evolving particularly slowly. Therefore, genome comparisons between two congeners of Branchiostoma revealed so many conserved noncoding elements (CNEs), that it was not clear how many are functional regulatory elements. To more effectively identify CNEs with potential regulatory functions, we compared noncoding sequences of genomes of the most phylogenetically distant cephalochordate genera, Asymmetron and Branchiostoma, which diverged approximately 120-160 million years ago. We found 113,070 noncoding elements conserved between the two species, amounting to 3.3% of the genome. The genomic distribution, target gene ontology, and enriched motifs of these CNEs all suggest that many of them are probably cis regulatory elements. More than 90% of previously verified amphioxus regulatory elements were re-captured in this study. A search of the cephalochordate CNEs around 50 developmental genes in several vertebrate genomes revealed eight CNEs conserved between cephalochordates and vertebrates, indicating sequence conservation over >500 million years of divergence. The function of five CNEs was tested in reporter assays in zebrafish, and one was also tested in amphioxus. All five CNEs proved to be tissue-specific enhancers. Taken together, these findings indicate that even though Branchiostoma and Asymmetron are distantly related, as they are evolving slowly, comparisons between them are likely optimal for identifying most of their tissue-specific cis-regulatory elements laying the foundation for functional characterizations and a better understanding of the evolution of developmental regulation in cephalochordates. PMID- 27412607 TI - Splice Sites Seldom Slide: Intron Evolution in Oomycetes. AB - We examine exon junctions near apparent amino acid insertions and deletions in alignments of orthologous protein-coding genes. In 1,917 ortholog families across nine oomycete genomes, 10-20% of introns are near an alignment gap, indicating at first sight that splice-site displacements are frequent. We designed a robust algorithmic procedure for the delineation of intron-containing homologous regions, and combined it with a parsimony-based reconstruction of intron loss, gain, and splice-site shift events on a phylogeny. The reconstruction implies that 12% of introns underwent an acceptor-site shift, and 10% underwent a donor site shift. In order to offset gene annotation problems, we amended the procedure with the reannotation of intron boundaries using alignment evidence. The corresponding reconstruction involves much fewer intron gain and splice-site shift events. The frequency of acceptor- and donor-side shifts drops to 4% and 3%, respectively, which are not much different from what one would expect by random codon insertions and deletions. In other words, gaps near exon junctions are mostly artifacts of gene annotation rather than evidence of sliding intron boundaries. Our study underscores the importance of using well-supported gene structure annotations in comparative studies. When transcription evidence is not available, we propose a robust ancestral reconstruction procedure that corrects misannotated intron boundaries using sequence alignments. The results corroborate the view that boundary shifts and complete intron sliding are only accidental in eukaryotic genome evolution and have a negligible impact on protein diversity. PMID- 27412608 TI - Osmoadaptative Strategy and Its Molecular Signature in Obligately Halophilic Heterotrophic Protists. AB - Halophilic microbes living in hypersaline environments must counteract the detrimental effects of low water activity and salt interference. Some halophilic prokaryotes equilibrate their intracellular osmotic strength with the extracellular milieu by importing inorganic solutes, mainly potassium. These "salt-in" organisms characteristically have proteins that are highly enriched with acidic and hydrophilic residues. In contrast, "salt-out" halophiles accumulate large amounts of organic solutes like amino acids, sugars and polyols, and lack a strong signature of halophilicity in the amino acid composition of cytoplasmic proteins. Studies to date have examined halophilic prokaryotes, yeasts, or algae, thus virtually nothing is known about the molecular adaptations of the other eukaryotic microbes, that is, heterotrophic protists (protozoa), that also thrive in hypersaline habitats. We conducted transcriptomic investigations to unravel the molecular adaptations of two obligately halophilic protists, Halocafeteria seosinensis and Pharyngomonas kirbyi Their predicted cytoplasmic proteomes showed increased hydrophilicity compared with marine protists. Furthermore, analysis of reconstructed ancestral sequences suggested that, relative to mesophiles, proteins in halophilic protists have undergone fewer substitutions from hydrophilic to hydrophobic residues since divergence from their closest relatives. These results suggest that these halophilic protists have a higher intracellular salt content than marine protists. However, absence of the acidic signature of salt-in microbes suggests that Haloc. seosinensis and P. kirbyi utilize organic osmolytes to maintain osmotic equilibrium. We detected increased expression of enzymes involved in synthesis and transport of organic osmolytes, namely hydroxyectoine and myo-inositol, at maximal salt concentration for growth in Haloc. seosinensis, suggesting possible candidates for these inferred organic osmolytes. PMID- 27412610 TI - Trends in the Evolution of Snake Toxins Underscored by an Integrative Omics Approach to Profile the Venom of the Colubrid Phalotris mertensi. AB - Only few studies on snake venoms were dedicated to deeply characterize the toxin secretion of animals from the Colubridae family, despite the fact that they represent the majority of snake diversity. As a consequence, some evolutionary trends observed in venom proteins that underpinned the evolutionary histories of snake toxins were based on data from a minor parcel of the clade. Here, we investigated the proteins of the totally unknown venom from Phalotris mertensi (Dipsadinae subfamily), in order to obtain a detailed profile of its toxins and to appreciate evolutionary tendencies occurring in colubrid venoms. By means of integrated omics and functional approaches, including RNAseq, Sanger sequencing, high-resolution proteomics, recombinant protein production, and enzymatic tests, we verified an active toxic secretion containing up to 21 types of proteins. A high content of Kunitz-type proteins and C-type lectins were observed, although several enzymatic components such as metalloproteinases and an L-amino acid oxidase were also present in the venom. Interestingly, an arguable venom component of other species was demonstrated as a true venom protein and named svLIPA (snake venom acid lipase). This finding indicates the importance of checking the actual protein occurrence across species before rejecting genes suggested to code for toxins, which are relevant for the discussion about the early evolution of reptile venoms. Moreover, trends in the evolution of some toxin classes, such as simplification of metalloproteinases and rearrangements of Kunitz and Wap domains, parallel similar phenomena observed in other venomous snake families and provide a broader picture of toxin evolution. PMID- 27412609 TI - Lineage-Specific Reductions of Plastid Genomes in an Orchid Tribe with Partially and Fully Mycoheterotrophic Species. AB - The plastid genome (plastome) of heterotrophic plants like mycoheterotrophs and parasites shows massive gene losses in consequence to the relaxation of functional constraints on photosynthesis. To understand the patterns of this convergent plastome reduction syndrome in heterotrophic plants, we studied 12 closely related orchids of three different lifeforms from the tribe Neottieae (Orchidaceae). We employ a comparative genomics approach to examine structural and selectional changes in plastomes within Neottieae. Both leafy and leafless heterotrophic species have functionally reduced plastid genome. Our analyses show that genes for the NAD(P)H dehydrogenase complex, the photosystems, and the RNA polymerase have been lost functionally multiple times independently. The physical reduction proceeds in a highly lineage-specific manner, accompanied by structural reconfigurations such as inversions or modifications of the large inverted repeats. Despite significant but minor selectional changes, all retained genes continue to evolve under purifying selection. All leafless Neottia species, including both visibly green and nongreen members, are fully mycoheterotrophic, likely evolved from leafy and partially mycoheterotrophic species. The plastomes of Neottieae span many stages of plastome degradation, including the longest plastome of a mycoheterotroph, providing invaluable insights into the mechanisms of plastome evolution along the transition from autotrophy to full mycoheterotrophy. PMID- 27412611 TI - Gene Expression Profiling in the Hibernating Primate, Cheirogaleus Medius. AB - Hibernation is a complex physiological response that some mammalian species employ to evade energetic demands. Previous work in mammalian hibernators suggests that hibernation is activated not by a set of genes unique to hibernators, but by differential expression of genes that are present in all mammals. This question of universal genetic mechanisms requires further investigation and can only be tested through additional investigations of phylogenetically dispersed species. To explore this question, we use RNA-Seq to investigate gene expression dynamics as they relate to the varying physiological states experienced throughout the year in a group of primate hibernators Madagascar's dwarf lemurs (genus Cheirogaleus). In a novel experimental approach, we use longitudinal sampling of biological tissues as a method for capturing gene expression profiles from the same individuals throughout their annual hibernation cycle. We identify 90 candidate genes that have variable expression patterns when comparing two active states (Active 1 and Active 2) with a torpor state. These include genes that are involved in metabolic pathways, feeding behavior, and circadian rhythms, as might be expected to correlate with seasonal physiological state changes. The identified genes appear to be critical for maintaining the health of an animal that undergoes prolonged periods of metabolic depression concurrent with the hibernation phenotype. By focusing on these differentially expressed genes in dwarf lemurs, we compare gene expression patterns in previously studied mammalian hibernators. Additionally, by employing evolutionary rate analysis, we find that hibernation-related genes do not evolve under positive selection in hibernating species relative to nonhibernators. PMID- 27412612 TI - The cost-effectiveness of family/family-based therapy for treatment of externalizing disorders, substance use disorders and delinquency: a systematic review. AB - BACKGROUND: Family therapy and family-based treatment has been commonly applied in children and adolescents in mental health care and has been proven to be effective. There is an increased interest in economic evaluations of these, often expensive, interventions. The aim of this systematic review is to summarize and evaluate the evidence on cost-effectiveness of family/family-based therapy for externalizing disorders, substance use disorders and delinquency. METHODS: A systematic literature search was performed in PubMed, Education Resource information Centre (ERIC), Psycinfo and Cochrane reviews including studies conducted after 1990 and before the first of August of 2013. Full economic evaluations investigating family/family-based interventions for adolescents between 10 and 20 years treated for substance use disorders, delinquency or externalizing disorders were included. RESULTS: Seven hundred thirty-one articles met the search criteria and 51 studies were initially selected. The final selection resulted in the inclusion of 11 studies. The quality of these studies was assessed. Within the identified studies, there was great variation in the specific type of family/family-based interventions and disorders. According to the outcomes of the checklists, the overall quality of the economic evaluations was low. Results varied by study. Due to the variations in setting, design and outcome it was not feasible to pool results using a meta-analysis. CONCLUSIONS: The quality of the identified economic evaluations of family/family-based therapy for treatment of externalizing disorders, adolescent substance use disorders and delinquency was insufficient to determine the cost-effectiveness. Although commonly applied, family/family-based therapy is costly and more research of higher quality is needed. PMID- 27412613 TI - Genetic diversity and structure in hill rice (Oryza sativa L.) landraces from the North-Eastern Himalayas of India. AB - BACKGROUND: Hill rices (Oryza sativa L.) are direct seeded rices grown on hill slopes of different gradients. These landraces have evolved under rainfed and harsh environmental conditions and may possess genes governing adaptation traits such as tolerance to cold and moisture stress. In this study, 64 hill rice landraces were collected from the state of Arunachal Pradesh of North-Eastern region of India, and assessed by agro-morphological variability and microsatellite markers polymorphism. Our aim was to use phenotypic and genetic diversity data to understand the basis of farmers' classification of hill rice landraces into two groups: umte and tening. Another goal was to understand the genetic differentiation of hill rices into Indica or japonica subspecies. RESULTS: According to farmers' classification, hill rices were categorized into two groups: umte (large-grained, late maturing) and tening (small-grained, early maturing). We did not find significant difference in days to 50 % flowering between the groups. Principal component analysis revealed that two groups can be distinguished on the basis of kernel length-to-width ration (KLW), kernel length (KL), grain length (GrL), grain length-to-width ration (GrLW) and plant height (Ht). Stepwise canonical discriminant analysis identified KL and Ht as the main discriminatory characters between the cultivar groups. Genetic diversity analysis with 35 SSR markers revealed considerable genetic diversity in the hill rice germplasm (gene diversity: 0.66; polymorphism information content: 0.62). Pair wise allelic difference between umte and tening groups was not statistically significant. The model-based population structure analysis showed that the hill rices were clustered into two broad groups corresponding to Indica and Japonica. The geographic distribution and cultivars grouping of hill rices were not congruent in genetic clusters. Both distance- and model-based approaches indicated that the hill rices were predominantly japonica or admixture among the groups within the subspecies. These findings were further supported by combined analysis hill rices with 150 reference rice accessions representing major genetic groups of rice. CONCLUSION: This study collected a valuable set of hill rice germplasm for rice breeding and for evolutionary studies. It also generated a new set of information on genetic and phenotypic diversity of hill rice landraces in North-Eastern region of India. The collected hill rices were mostly japonica or admixture among the subpopulations of Indica or Japonica. The findings are useful for utilization and conservation of hill rice germplasm. PMID- 27412614 TI - Incidence and prevalence of gout in Western Sweden. AB - BACKGROUND: The aim of the present study was to describe prevalence and trends in the incidence of gout and patterns of urate-lowering treatment (ULT) in the Western Swedish Health Care Region (WSHCR) from 2002 to 2012. METHODS: We used regional and national healthcare registers to estimate the prevalence and incidence of gout in 2012, and trends in incidence for each calendar year from 2005 to 2012. We also investigated the pattern of ULT for gout using the Swedish Prescribed Drug Register. RESULTS: In 2012, in the population aged 20 years and above, the prevalence of gout was 1.8 % (95 % confidence interval (CI) 1.77 to 1.82) and the incidence was 190 cases (95 % CI 180 to 200) per 100,000 person years. Applying more strict definitions for a gout case rendered a prevalence of 1.36 % (95 % CI 1.34 to 1.38) and 0.5 (95 % CI 0.49 to 0.51) per 100,000 person years, respectively. The incidence of gout increased steadily and significantly from 2005 to 2012, with an almost 50 % increase in the total population. There was no significant difference in the prevalence of gout in rural compared to urban areas. ULT was dispensed to only 42 % of patients with gout in 2012 who had ever been diagnosed with gout during the preceding 10-year period. CONCLUSIONS: Gout is the most common arthritic disease in WSHCR, Sweden, and has increased substantially over the last decade, with only a minority of prevalent cases in 2012 receiving ULT. PMID- 27412615 TI - Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults. AB - BACKGROUND: Impairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria. METHODS: We conducted a cross-sectional study among older hypertensive male veterans with stage 1-4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders. RESULTS: Among 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m(2); 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (beta= - 0.42, p = 0.009 and beta= -0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD. CONCLUSIONS: Microvascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD. PMID- 27412616 TI - The incidence and worsening of newly diagnosed low back pain in a population of young male military recruits. AB - BACKGROUND: Low back pain (LBP) is a leading cause of referral to occupational health clinics and of consequent work absenteeism. There is lack of data concerning ages 18-21. The objective of our study was to evaluate the occurrence of newly diagnosed LBP and the recurrence and worsening of preexisting LBP in young male military recruits. METHODS: In this retrospective cohort study, we examined the medical history of army recruits during the 30-month period after their induction into the Israel Defense Forces (IDF). The duty status of soldiers in combat units (CU), maintenance units (MU) and administrative units (AU) was evaluated according to their morbidity. The study's end point was defined as significant findings on clinical examination with presence of neurological deficits which correlate to radiological findings on CT or MRI showing herniated disks, spinal stenosis or pressure on neurological roots. RESULTS: The annual incidence rate of LBP in a total of 159,295 recruits was 0.05 %. The relative risk (RR) for developing LBP was significantly higher among subjects who were assigned to AU as compared to CU and MU in all LBP categories. The RR for LBP recurrence in soldiers with a positive history of LBP (categories 3 and 4) was 4.1 and 10.7 compare to category 1 respectively. CONCLUSIONS: The lower than expected overall incidence rate of 0.05 % reflects the fact that severe LBP occurrences are not common at this age group. This finding is a more truthful reflection of LBP occurrence rates relative to other studies since the end point is based on precise clinical definitions in medical records and not on questionnaires, as in most studies. The RR for developing LBP was significantly higher among subjects who were assigned to AU as compared to CU and MU in all LBP categories. Childhood history of LBP was found as a significant risk factor for LBP exacerbations at adulthood. Positive history of LBP was found as a risk factor for the recurrence of LBP in all occupation types and particularly in sedentary ones. PMID- 27412617 TI - Duodenal-jejunal bypass changes the composition of the gut microbiota. AB - This study investigated the composition of the gut microbiota in rats after duodenal-jejunal bypass (DJB) in comparison to that in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Six male 16-week-old OLETF rats were divided into three groups: a DJB group, a sham operation group, and a daily injection with a GLP-1 receptor agonist (liraglutide) group. The gut microbiota of the three groups was analyzed at postoperative week 8 using the PCR-clone library method targeting the 16S ribosomal RNA gene. The DJB group showed a decrease in Bacteroidia in comparison to the other two groups (DJB, 3.9 %/2.8 %; sham, 10.8 %/11.6 %; liraglutide, 33.2 %/14.1 %). In addition, DJB markedly increased the ratio of Gammaproteobacteria (DJB, 10.8 %/13.7 %; sham, 0.2 %/1.2 %; liraglutide, 0 %/0.1 %). DJB changes the composition of gut microbiota; these changes might be the factors that contribute to the effects of DJB. PMID- 27412618 TI - Non-equilibrium dynamics of magnetically anisotropic particles under oscillating fields. AB - In this article, we demonstrate how magnetic anisotropy of colloidal particles can give rise to unusual dynamics and controllable rearrangements under time dependent fields. As an example, we study spherical particles with a radially off centered net magnetic moment in an oscillating field. Based on complementary data from a numerical simulation of spheres with shifted dipole and experimental observations from particles with hemispherical ferromagnetic coating, it is explained on a two particle basis how this magnetic anisotropy causes nontrivial rotational motion and magnetic reorientation. We further present the behavior of larger ensembles of coated particles. It illustrates the potential for controlled reconfiguration based on the presented two-particle dynamics. PMID- 27412621 TI - Illuminating solid gas storage in confined spaces - methane hydrate formation in porous model carbons. AB - Methane hydrate nucleation and growth in porous model carbon materials illuminates the way towards the design of an optimized solid-based methane storage technology. High-pressure methane adsorption studies on pre-humidified carbons with well-defined and uniform porosity show that methane hydrate formation in confined nanospace can take place at relatively low pressures, even below 3 MPa CH4, depending on the pore size and the adsorption temperature. The methane hydrate nucleation and growth is highly promoted at temperatures below the water freezing point, due to the lower activation energy in ice vs. liquid water. The methane storage capacity via hydrate formation increases with an increase in the pore size up to an optimum value for the 25 nm pore size model carbon, with a 173% improvement in the adsorption capacity as compared to the dry sample. Synchrotron X-ray powder diffraction measurements (SXRPD) confirm the formation of methane hydrates with a sI structure, in close agreement with natural hydrates. Furthermore, SXRPD data anticipate a certain contraction of the unit cell parameter for methane hydrates grown in small pores. PMID- 27412620 TI - Persisting and Increasing Neutrophil Infiltration Associates with Gastric Carcinogenesis and E-cadherin Downregulation. AB - H. pylori-induced chronic inflammation is considered the most important cause of gastric cancer. The actual process how chronic inflammation triggers gastric carcinogenesis is still not clear. In this study, neutrophils and relative markers in gastric cancer development were examined with immunohistochemistry and fluorescence RNA in situ hybridization methods. On average, 24 times more neutrophils were found in gastric cancer tissues and about 9 times more neutrophils were found in gastric intestinal metaplasia tissues comparing to normal gastric tissue controls. CagA(+) H. pylori infection in cancer adjacent tissues or EBV infection in cancer tissues did not increase neutrophil infiltration into gastric cancer tissues significantly. Neutrophil density was positively correlated with cell proliferation while negatively correlated with E cadherin intensity. E-cadherin is also transcriptionally downregulated in gastric cancer tissues comparing to adjacent tissue controls. The increased neutrophils in the gastric cancer tissues appear to be related to increased chemoattractant IL-8 levels. In gastric cancers, neutrophil numbers were higher comparing to cancer adjacent tissues and not associated with patient ages, tumor invasion depth, tumor staging, metastasis or cancer types. The conclusion is that persisting and increasing neutrophil infiltration is associated with E-cadherin downregulation, cell proliferation and gastric carcinogenesis. PMID- 27412619 TI - Wheelchair use and lipophilic statin medications may influence bone loss in chronic spinal cord injury: findings from the FRASCI-bone loss study. AB - : We identified a protective bone effect at the knee with lipophilic statin use in individuals with chronic spinal cord injury. Lipophilic statin users gained bone at the knee compared to non-users and wheelchair users lost bone compared to walkers. Ambulation and or statins may be effective osteogenic interventions in chronic spinal cord injury (SCI). INTRODUCTION: SCI increases the risk of osteoporosis and low-impact fractures, particularly at the knee. However, during the chronic phase of SCI, the natural history and factors associated with longitudinal change in bone density remain poorly characterized. In this study, we prospectively assessed factors associated with change in bone density over a mean of 21 months in 152 men and women with chronic SCI. METHODS: A mixed model procedure with repeated measures was used to assess predictors of change in bone mineral density (PROC MIXED) at the distal femur and proximal tibia. Factors with a p value of <0.10 in the univariate mixed models, as well as factors that were deemed clinically significant (gender, age, and walking status), were assessed in multivariable models. Factors with a p value of <=0.05 were included in the final model. RESULTS: We found no association between bone loss and traditional osteoporosis risk factors, including age, gender, body composition, or vitamin D level or status (normal or deficient). In both crude and fully adjusted models, wheelchair users lost bone compared to walkers. Similarly, statin users gained bone compared to nonusers. CONCLUSIONS: The statin finding is supported by reports in the general population where statin use has been associated with a reduction in bone loss and fracture risk. Our results suggest that both walking and statins may be effective osteogenic therapies to mitigate bone loss and prevent osteoporosis in chronic SCI. Our findings also suggest that loss of mechanical loading and/or neuronal factors contribute more to disuse osteoporosis than traditional osteoporosis risk factors. PMID- 27412622 TI - Mediterranean circulation perturbations over the last five centuries: Relevance to past Eastern Mediterranean Transient-type events. AB - The Eastern Mediterranean Transient (EMT) occurred in the Aegean Sea from 1988 to 1995 and is the most significant intermediate-to-deep Mediterranean overturning perturbation reported by instrumental records. The EMT was likely caused by accumulation of high salinity waters in the Levantine and enhanced heat loss in the Aegean Sea, coupled with surface water freshening in the Sicily Channel. It is still unknown whether similar transients occurred in the past and, if so, what their forcing processes were. In this study, sediments from the Sicily Channel document surface water freshening (SCFR) at 1910 +/- 12, 1812 +/- 18, 1725 +/- 25 and 1580 +/- 30 CE. A regional ocean hindcast links SCFR to enhanced deep-water production and in turn to strengthened Mediterranean thermohaline circulation. Independent evidence collected in the Aegean Sea supports this reconstruction, showing that enhanced bottom water ventilation in the Eastern Mediterranean was associated with each SCFR event. Comparison between the records and multi-decadal atmospheric circulation patterns and climatic external forcings indicates that Mediterranean circulation destabilisation occurs during positive North Atlantic Oscillation (NAO) and negative Atlantic Multidecadal Oscillation (AMO) phases, reduced solar activity and strong tropical volcanic eruptions. They may have recurrently produced favourable deep-water formation conditions, both increasing salinity and reducing temperature on multi-decadal time scales. PMID- 27412624 TI - Double deuterated acetylacetone in neon matrices: infrared spectroscopy, photoreactivity and the tunneling process. AB - The effect of deuteration of acetylacetone (C5O2H8) is explored by means of IR spectroscopy of its single and double deuterated isotopologues trapped in neon matrices. The whole vibrational spectra of chelated enols are very sensitive to the H-D exchange of the hydrogen atom involved in the internal hydrogen bond. UV excitation of double deuterated acetylacetone isolated in neon matrices induces the formation of four open enol isomers which can be divided into two groups of two conformers, depending on their formation kinetics. Within each group, one conformer is more stable than the other: slow conformer interconversion due to a tunneling process is observed in the dark at low temperature. Moreover, IR laser irradiation at the OD stretching overtone frequency is used to induce interconversion either from the most stable to the less stable conformer or the opposite, depending on the excitation wavelength. The interconversion process is of great help to assign conformers which are definitively identified by comparison between experimental and calculated IR spectra. Kinetic constants of the tunneling process at play are theoretically estimated and agree perfectly with experiments, including previous experiments with the totally hydrogenated acetylacetone [Lozada Garcia et al., Phys. Chem. Chem. Phys., 2012, 14, 3450]. PMID- 27412623 TI - Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species. AB - Apolipoprotein E (apoE), involved in cholesterol and lipid metabolism, also influences cognitive function and injury repair. In humans, apoE is expressed in three isoforms. E4 is a risk factor for age-related cognitive decline and Alzheimer's disease, particularly in women. E4 might also be a risk factor for developing behavioral and cognitive changes following (56) Fe irradiation, a component of the space environment astronauts are exposed to during missions. These changes might be related to enhanced generation of reactive oxygen species (ROS). In this study, we compared the behavioral and cognitive performance of sham-irradiated and irradiated wild-type (WT) mice and mice expressing the human E3 or E4 isoforms, and assessed the generation of ROS in hippocampal slices from these mice. E4 mice had greater anxiety-like and conditioned fear behaviors than WT mice, and these genotype differences were associated with greater levels of ROS in E4 than WT mice. The greater generation of ROS in the hippocampus of E4 than WT mice might contribute to their higher anxiety levels and enhanced fear conditioning. In E4, but not WT, mice, phorbol-12-myristate-13-acetate-treated hippocampal slices showed more dihydroxy ethidium oxidation in sham-irradiated than irradiated mice and hippocampal heme oxygenase-1 levels were higher in irradiated than sham-irradiated E4 mice. Mice with apolipoprotein E4 (E4), a risk factor for Alzheimer's disease, have greater anxiety-like and conditioned fear behaviors than wild-type (WT) mice. Generation of reactive oxygen species (ROS, in red) 3 months following (56) Fe irradiation, a component of the space environment astronauts are exposed to, is more pronounced in the hippocampus of E4 than WT mice. In E4, but not WT, mice, hippocampal levels of the oxidative stress-relevant marker heme oxygenase-1 are higher in irradiated than sham irradiated E4 mice. PMID- 27412626 TI - Cost-effectiveness of interferon-gamma release assays for tuberculosis screening in nursing homes. AB - Tuberculosis (TB) in older people is a significant public health problem in low TB-incidence countries. Older persons have increased TB incidence, higher reactivation and mortality. A delay in diagnosis and initiation of TB treatment in patients with atypical clinical and radiological features is a significant factor of widespread transmission. This study aimed to evaluate the cost effectiveness of interferon-gamma release assays [IGRAs; QuantiFERON(r)-TB Gold In-Tube (QFT) and T-SPOT(r).TB (T-SPOT)] compared to the tuberculin skin test (TST) and chest X-ray (CXR) examination for TB screening for nursing homes. Decision trees and Markov models were constructed using a societal perspective on a lifetime horizon. Seven strategies: no screening, TST, QFT, T-SPOT, TST followed by QFT, TST followed by T-SPOT, and CXR were considered. QFT [US$ 401.9, 4.36 707 QALY (year 2014 values)] was the most cost-effective at the willingness to-pay level of US$ 50 000/QALY gained. TST followed by QFT was the most cost effective in residents with comorbidities. CXR was less cost-effective. Cost effectiveness was sensitive to latent TB infection (LTBI) rate and bacillus Calmette-Guerin vaccination rate. Effective LTBI screening using IGRA is recommended to prevent TB transmission not only in nursing homes but also in local communities in low-incidence countries. PMID- 27412627 TI - Erratum to: Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy. PMID- 27412625 TI - Evidence-based practice, research utilization, and knowledge translation in chiropractic: a scoping review. AB - BACKGROUND: Evidence-based practice (EBP) gaps are widespread across health disciplines. Understanding factors supporting the uptake of evidence can inform the design of strategies to narrow these EBP gaps. Although research utilization (RU) and the factors associated with EBP have been reported in several health disciplines, to date this area has not been reviewed comprehensively in the chiropractic profession. The purpose of this review was to report on the current state of knowledge on EBP, RU, and knowledge translation (KT) in chiropractic. METHODS: A scoping review using the Arksey and O'Malley framework was used to systematically select and summarize existing literature. Searches were conducted using a combination of keywords and MeSH terms from the earliest date available in each database to May 2015. Quantitative and thematic analyses of the selected literature were conducted. RESULTS: Nearly 85 % (56/67) of the included studies were conducted in Canada, USA, UK or Australia. Thematic analysis for the three categories (EBP, RU, KT) revealed two themes related to EBP (attitudes and beliefs of chiropractors; implementation of EBP), three related to RU (guideline adherence; frequency and sources of information accessed; and perceived value of websites and search engines), and three related to KT (knowledge practice gaps; barriers and facilitators to knowledge use; and selection, tailoring, and implementation of interventions). EBP gaps were noted in the areas of assessment of activity limitation, determination of psychosocial factors influencing pain, general health indicators, establishing a prognosis, and exercise prescription. While most practitioners believed EBP and research to be important and a few studies suggested that traditional and online educational strategies could improve patient care, use of EBP and guideline adherence varied widely. CONCLUSION: Findings suggest that the majority of chiropractors hold favourable attitudes and beliefs toward EBP. However, much remains to be done for chiropractors to routinely apply evidence into clinical practice. Educational strategies aimed at practicing chiropractors can lead to more EBP and improved patient care. The chiropractic profession requires more robust dissemination and implementation research to improve guideline adherence and patient health outcomes. PMID- 27412629 TI - Comparison of Functional Recovery is Crucial for Implementing ERAS. PMID- 27412628 TI - Multifocal Versus Solitary Papillary Thyroid Carcinoma. AB - BACKGROUND: Papillary Thyroid Carcinoma (PTC) which accounts for >85 % of all thyroid cancers in iodine-rich areas, appears either as a single tumor or as two or more, neoplastic foci within the thyroid gland (Multifocal PTC). We present the comparative results between solitary and MFC PTC. MATERIALS AND METHODS: Demographics, tumor characteristics (size, laterality, foci number, histologic subtype) and TNM staging were compared between solitary and MFPTC patients. The presence of lymphocytic or Hashimoto's thyroditis was also recorded. RESULTS: From January 2008 to December 2012, among 647 PTC patients, 241(37.2 %) had MFPTC 177 females (73.4 %) and 64 males (26.6 %), mean age 48.5 years (range 12-87). Mean number of tumor foci was 3.3 (range 2-26). MFPTC patients presented with more advanced T stage (28.2 vs. 18.7 %, p = 0.01) and more LN metastases (28.6 vs. 15.5 %, p < 0.001). Foci number correlates with male gender and LN metastases (p = 0.014 and p = 0.019, respectively). Central (N1a) or lateral (N1b) LN involvement correlates strongly with male gender (p = 0.024) and younger age (p < 0.001). The follicular variant was the next most frequent histologic subtype associated with extremely rare LN metastases. CONCLUSION: MFPTC comprises a more aggressive form of papillary thyroid cancer since it is associated with more frequent N1a/ N1b disease and occurs more frequently in T3/T4 patients. MFPTC foci number correlates with male gender and LN metastases. PMID- 27412630 TI - Gallstones and Bariatric Surgery: To Treat or Not to Treat? AB - BACKGROUND: Obesity and rapid weight loss after bariatric surgery are risk factors for gallstone disease. OBJECTIVES: The present study sought to evaluate the feasibility of selective concomitant cholecystectomy only in patients with symptomatic disease and study risk factors for the development of symptomatic gallstones after bariatric surgery. METHODS: Between January 2010 and December 2012, 734 consecutive patients presenting to our institution underwent bariatric surgery. From these, 81 patients were excluded due to prior or concurrent cholecystectomy. The remaining 653 patients with in situ gallbladder were followed for 12 months and were clinically screened for symptomatic or complicated cholelithiasis. Clinical and demographic characteristics were compared at baseline and 12 months after surgery. RESULTS: Of the 653 patients with in situ gallbladder, only 24 (3.3 %) developed symptomatic gallstones and only nine presented complicated disease. None of the patients with asymptomatic disease at the time of surgery progressed to symptomatic or complicated disease. Patients who developed symptomatic disease were not significantly different, although there was a trend toward longer obesity evolution, lower insulin levels, and lower hepatic enzymes level. A multivariate regression analysis revealed that patients with gastric sleeve were more likely to develop symptomatic gallstones. CONCLUSIONS: Although further studies are required, the management of gallstones in morbidly obese patients should not be different from normal-weight patients. Therefore, performing a laparoscopic cholecystectomy only in symptomatic patients is an effective approach and asymptomatic gallstones should not be treated at the time of bariatric surgery. PMID- 27412631 TI - Does Intraoperative Systematic Bacterial Sampling During Complete Cytoreductive Surgery (CRS) with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) Influence Postoperative Treatment? A New Predictive Factor for Postoperative Abdominal Infectious Complications. AB - BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an emerging curative treatment option for patients with peritoneal carcinomatosis. It has a long-term survival benefit but is associated with high rates of morbidity, ranging from 12 % to 65 %, mainly due to infectious complications. We sought to evaluate the clinical relevance of routine intraoperative bacteriological sampling following CRS/HIPEC. STUDY DESIGN: Between November 2010 and December 2014, every patients receiving CRS/HIPEC were included. Three samples were routinely collected from standardized locations for intraperitoneal rinsing liquid bacteriological analysis (RLBA) after completion of HIPEC. The clinical and surgical features, bacteriological results, and short term outcomes were retrospectively reviewed. RESULTS: The overall mortality and morbidity rates were 5 and 45 %, respectively. Among the 75 included patients, 40 % (n = 30) had at least one positive bacterial culture. Risk factors for a positive culture were colorectal resection (adjusted hazard ratio [HR] = 3.072, 95 % CI 1.843-8.004; p = 0.009) and blood loss >1000 mL (HR = 4.272, 95 % CI 1.080-18.141; p = 0.031). Among 26 (35 %) patients with abdominal infectious complications, 13 (17 %) experienced isolated complications. A positive RLBA result was independently associated with abdominal infectious complications (HR = 5.108, 95 % CI 1.220-16.336; p = 0.024) and isolated abdominal infectious complications (HR = 4.199, 95 % CI 1.064-15.961; p = 0.04). CONCLUSIONS: Forty percent of the RLBA samples obtained following CRS/HIPEC tested positive for bacteria. Bacterial sampling of rinsing liquid should be systematically performed. An aggressive and immediate antibiotic strategy needs to be evaluated. PMID- 27412633 TI - Smoking is a risk factor for development of adult T-cell leukemia/lymphoma in Japanese human T-cell leukemia virus type-1 carriers. AB - BACKGROUND AND PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1); no effective methods have yet been identified to prevent development of ATLL in carriers of HTLV-1. This study investigated the association between cigarette smoking and the risk of ATLL development among Japanese carriers of HTLV-1. METHODS: This study examined the association between smoking and development of ATLL in a cohort of 1,332 Japanese HTLV-1 carriers aged 40-69 years free of ATLL at baseline from two different HTLV-1-endemic areas of Japan. Cox proportional hazards models adjusted for sex, geographic area, age at baseline, and alcohol drinking were used to estimate the effect of cigarette smoking on ATLL development. RESULTS: Between 1993 and 2012, 25 new ATLL cases were identified among these subjects. The overall crude incidence rate for ATLL was 1.08 per 1,000 person-years among HTLV-1 carriers and was higher among male carriers than among female carriers (2.21 vs. 0.74). The risk of ATLL development increased significantly with increasing numbers of cigarettes smoked per day (hazard ratio for every increment of 20 cigarettes, 2.03; 95 % confidence interval (CI) 1.13 3.66 overall, 2.07 (95 % CI 1.13-3.73) in male carriers). CONCLUSIONS: Cigarette smoking may influence ATLL development among HTLV-1 carriers in Japan. PMID- 27412632 TI - Tumour heterogeneity: principles and practical consequences. AB - Two major reasons compel us to study tumour heterogeneity: firstly, it represents the basis of acquired therapy resistance, and secondly, it may be one of the major sources of the low level of reproducibility in clinical cancer research. The present review focuses on the heterogeneity of neoplastic disease, both within the primary tumour and between primary tumour and metastases. We discuss different levels of heterogeneity and the current understanding of the phenomenon, as well as imminent developments relevant for clinical research and diagnostic pathology. It is necessary to develop new tools to study heterogeneity and new biomarkers for heterogeneity. Established and new in situ methods will be very useful. In future studies, not only clonal heterogeneity needs to be addressed but also non-clonal phenotypic heterogeneity which might be important for therapy resistance. We also review heterogeneity established in major tumour types, in order to explore potential similarities that might help to define new strategies for targeted therapy. PMID- 27412634 TI - Advances in three-dimensional super-resolution nanoscopy. AB - Three-dimensional optical super-resolution imaging is capable of providing 3D visualization of cellular structures in nanoscale detail. The past decade has witnessed the blossoming of 3D super-resolution imaging technologies. In this review, we comprehensively discuss and compare the imaging depth, resolution enhancement, and imaging speed of the existing 3D super-resolution imaging techniques. PMID- 27412637 TI - Lung cancer screening. PMID- 27412636 TI - An unusual UMP C-5 methylase in nucleoside antibiotic polyoxin biosynthesis. AB - Polyoxin is a group of structurally-related peptidyl nucleoside antibiotics bearing C-5 modifications on the nucleoside skeleton. Although the structural diversity and bioactivity preference of polyoxin are, to some extent, affected by such modifications, the biosynthetic logic for their occurence remains obscure. Here we report the identification of PolB in polyoxin pathway as an unusual UMP C 5 methylase with thymidylate synthase activity which is responsible for the C-5 methylation of the nucleoside skeleton. To probe its molecular mechanism, we determined the crystal structures of PolB alone and in complexes with 5-Br UMP and 5-Br dUMP at 2.15 A, 1.76 A and 2.28 A resolutions, respectively. Loop 1 (residues 117-131), Loop 2 (residues 192-201) and the substrate recognition peptide (residues 94-102) of PolB exhibit considerable conformational flexibility and adopt distinct structures upon binding to different substrate analogs. Consistent with the structural findings, a PolB homolog that harbors an identical function from Streptomyces viridochromogenes DSM 40736 was identified. The discovery of UMP C5-methylase opens the way to rational pathway engineering for polyoxin component optimization, and will also enrich the toolbox for natural nucleotide chemistry. PMID- 27412635 TI - Regulation of TAZ in cancer. AB - TAZ, a transcriptional coactivator with PDZ-binding motif, is encoded by WWTR1 gene (WW domain containing transcription regulator 1). TAZ is tightly regulated in the hippo pathway-dependent and -independent manner in response to a wide range of extracellular and intrinsic signals, including cell density, cell polarity, F-actin related mechanical stress, ligands of G protein-coupled receptors (GPCRs), cellular energy status, hypoxia and osmotic stress. Besides its role in normal tissue development, TAZ plays critical roles in cell proliferation, differentiation, apoptosis, migration, invasion, epithelial mesenchymal transition (EMT), and stemness in multiple human cancers. We discuss here the regulators and regulation of TAZ. We also highlight the tumorigenic roles of TAZ and its potential therapeutic impact in human cancers. PMID- 27412638 TI - To compare cost effectiveness of 'Kangaroo Ward Care' with 'Intermediate intensive care' in stable very low birth weight infants (birth weight < 1100 grams): a randomized control trial. AB - BACKGROUND: To compare cost effectiveness of 'Kangaroo Ward Care' with 'Intermediate Intensive Care' in stable very low birth weight infants (birth weight < 1100 g). METHODS: This is the secondary analysis of the study in which we have analysed the cost effectiveness of 'Kangaroo ward care' (KWC) with 'Intermediate Intensive Care' (IIC). In this randomized control trial 141 infants (less than 1100 g and <= 32 weeks at birth) were enrolled, 71 were randomized to KWC group and 70 to IIC group, once the infant reached a weight of 1150 g. Infants randomized to KWC group were shifted to the Kangaroo ward immediately after randomization. Infants randomized to IIC group were shifted to the Kangaroo ward once the infant reached 1250 g. RESULTS: Cost incurred by the patient in both the groups from the time of randomization to hospital discharge was calculated. The hospital costs were determined by "top-down" accounting methods and out of pocket expenditure of parents from standard "bottom-up" cost accounting methods. There was significant reduction in neonatal charges in KWC group post-randomization {41591.9 +/- 21712.8 INR vs 75388.8 +/- 25532.2 INR; p < 0.001}). The separate "top-down" and "bottom-up" cost analysis showed that there was significant reduction of hospital and parents expenditure in KWC group when compared to IIC group (p < 0.001). There was significant saving of around 33800 INR (USD) in the KWC group for each patient. CONCLUSION: Initiating early shifting to Kangaroo ward is cost effective intervention and have huge monetary implication in resource poor countries. (CTRI/2014/05/004625, retrospectively registered, Registered on: 26/05/2014). CLINICAL TRIAL REGISTRATION: Clinical trial registry of India CTRI/2014/05/004625 ( http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=7640&EncHid=&userName=CTRI/20 4/05/004625 ) Registered on: 26/05/2014. Date of enrolment of the first participant to the trial: 13/11/2013. PMID- 27412639 TI - Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD. AB - OBJECTIVES: Epilepsy, febrile seizures, and attention-deficit/hyperactivity disorder (ADHD) are disorders of the central nervous system and share common risk factors. Our goal was to examine the association in a nationwide cohort study with prospective follow-up and adjustment for selected confounders. We hypothesized that epilepsy and febrile seizures were associated with subsequent ADHD. METHODS: A population-based cohort of all children born in Denmark from 1990 through 2007 was followed up until 2012. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for ADHD were estimated by using Cox regression analysis, comparing children with epilepsy and febrile seizure with those without these disorders, adjusted for socioeconomic and perinatal risk factors, as well as family history of neurologic and psychiatric disorders. RESULTS: A total of 906 379 individuals were followed up for 22 years (~10 million person-years of observation); 21 079 individuals developed ADHD. Children with epilepsy had a fully adjusted IRR of ADHD of 2.72 (95% CI, 2.53-2.91) compared with children without epilepsy. Similarly, in children with febrile seizure, the fully adjusted IRR of ADHD was 1.28 (95% CI, 1.20-1.35). In individuals with both epilepsy and febrile seizure, the fully adjusted IRR of ADHD was 3.22 (95% CI, 2.72-3.83). CONCLUSIONS: Our findings indicate a strong association between epilepsy in childhood and, to a lesser extent, febrile seizure and subsequent development of ADHD, even after adjusting for socioeconomic and perinatal risk factors, and family history of epilepsy, febrile seizures, or psychiatric disorders. PMID- 27412641 TI - You lookin' at me? PMID- 27412640 TI - Improving Discharge Efficiency in Medically Complex Pediatric Patients. AB - BACKGROUND AND OBJECTIVE: Children with medical complexity have unique needs when facilitating transitions from hospital to home. Defining readiness for discharge is challenging, and preparation requires coordination of family, education, equipment, and medications. Our multidisciplinary team aimed to increase the percentage of medically complex hospital medicine patients discharged within 2 hours of meeting medical discharge goals from 50% to 80%. METHODS: We used quality improvement methods to identify key drivers and inform interventions. Medical discharge goals were defined on admission for each patient. Interventions included implementation of a complex care inpatient team with electronic admission order set, weekly care coordination rounds, needs assessment tool, and medication pathway. The primary measure, percentage of patients discharged within 2 hours of meeting medical discharge goals, was followed on a run chart. The secondary measures, pre- and post-intervention length of stay and 30-day readmission rate, were compared by using Wilcoxon rank-sum and chi(2) tests, respectively. RESULTS: The percentage of medically complex patients discharged within 2 hours of meeting medical discharge goals improved from 50% to 88% over 17 months and sustained for 6 months. In preintervention-postintervention comparison, median length of stay did not change (3.1 days [interquartile range, 1.8-7.0] vs 2.9 days [interquartile range, 1.7-6.1]; P = .67) and 30-day readmission rate was not impacted (30.7% vs 26.4%; P = .51). CONCLUSIONS: Efficient discharge for medically complex patients requires support of a multidisciplinary team to proactively address discharge needs, ensuring patients are ready for discharge when medical goals are met. PMID- 27412643 TI - Naked-eye sensitive detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) based on a horseradish peroxidase catalytic colorimetric system with Cu(ii). AB - In this paper, a novel colorimetric method for the detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) was designed based on a Cu(2+) horseradish peroxidase (HRP)-3,3',5,5'-tetra-methylbenzidine (TMB)-H2O2 system. In the presence of ALP, l-ascorbic acid-2-phosphate (AAP) could be hydrolyzed to ascorbic acid which could reduce Cu(2+) to Cu(+) to inhibit the enzymatic activity of HRP in the colorimetric system. The change in absorbance was found to be proportional to the ALP concentration with a linear detection range and a limit of detection of 5.4 mU mL(-1). In the presence of PPi, because Cu(2+) was chelated by PPi, the conversion of Cu(ii) by AA was effectively inhibited. The color of the HRP-TMB-H2O2 system with Cu(2+) showed blue. The HRP-TMB-H2O2 system with the Cu(2+) colorimetric system could also detect PPi with a satisfying result. In summary, this method possesses sensitivity, reproducibility, and cost effectiveness without labelling and separation and the use of a colorimetric method is more in line with the requirements of on-site detection and green chemistry. PMID- 27412642 TI - Isolated symptomatic middle cerebral artery stenosis in young adults: clinical prognosis and vascular change. AB - BACKGROUND AND PURPOSE: To investigate the clinical prognosis and vascular outcome of ischemic stroke patients with isolated symptomatic middle cerebral artery stenosis, and further analysis of the predictors associated with the results. METHODS: Ischemic stroke patients aged 18-55 years old with isolated symptomatic middle cerebral artery stenosis were evaluated and followed up prospectively for six months. Logistic regression was used to detect predictors of ipsilateral stroke recurrence, and factors associated with the dynamic changes of lesion vascular were analyzed. RESULTS: Eighty patients were included, with a mean age of 41.8 +/- 8.3 years old. Males predominated in this cohort at a proportion of 78.8% (63/80). Twenty percent of patients presented with ipsilateral ischemic stroke recurrence during this time but mostly with a good outcome (70% mRS <= 1); multiple logistic regression indicated that diabetes mellitus is an independent predictor for stroke recurrence; 38.6% patients presented with significant vascular changes during the follow-up, with progression in 12 (17.1%) and regression in 15 (21.4%) patients individually. No variables were detected as predictors of cerebral vascular progression. CONCLUSION: Isolated symptomatic middle cerebral artery stenosis in young adults had unaccepted high rates of recurrence but comparatively good prognosis; despite the dramatic change of lesion artery in the short period after stroke, no factors were detected as the probable factors associated with the dynamic process. PMID- 27412644 TI - Shell-ferromagnetism of nano-Heuslers generated by segregation under magnetic field. AB - We report on a new functional property in an AF martensitic Heusler Ni50Mn45In5, which when annealed at high temperatures under a magnetic field, segregates and forms Ni50Mn25In25 Heusler precipitates embedded in a Ni50Mn50 matrix. The precipitates are paramagnetic whereas the matrix is antiferromagnetic. However, the spins at the interface with the Ni50Mn50 matrix align with the field during their nucleation and growth and become strongly pinned in the direction of the applied field during annealing, whereas the core spins become paramagnetic. This shell-ferromagnetism persists up to 600 K and is so strongly pinned that the remanent magnetization remains unchanged, even when the field is reversed or when the temperature is cycled between low temperatures and close to the annealing temperature. PMID- 27412645 TI - The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1beta and TNF-alpha. AB - Ouabain is a steroid hormone that binds to the enzyme Na(+), K(+) - ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1beta and TNF-alpha are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1beta and TNF-alpha also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1beta and TNF-alpha could be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1beta or anti TNF-alpha antibodies. In agreement, IL-1beta or TNF-alpha increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-alpha and IL-1beta from retinal cell cultures. Interestingly, TNF-alpha and IL-1beta regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF alpha and IL-1beta signaling pathways leading to an increase in retinal ganglion cell survival. PMID- 27412646 TI - Local Diameter, Wall Stress, and Thrombus Thickness Influence the Local Growth of Abdominal Aortic Aneurysms. AB - PURPOSE: To investigate the influence of the local diameter, the intraluminal thrombus (ILT) thickness, and wall stress on the local growth rate of abdominal aortic aneurysms. METHODS: The infrarenal aortas of 90 asymptomatic abdominal aortic aneurysm (AAA) patients (mean age 70 years; 77 men) were retrospectively reconstructed from at least 2 computed tomography angiography scans (median follow-up of 1 year) and biomechanically analyzed with the finite element method. Each individual AAA model was automatically sliced orthogonally to the lumen centerline and represented by 100 cross sections with corresponding diameters, ILT thicknesses, and wall stresses. The data were grouped according to these parameters for comparison of differences among the variables. RESULTS: Diameter growth was continuously distributed over the entire aneurysm sac, reaching absolute and relative median peaks of 3.06 mm/y and 7.3%/y, respectively. The local growth rate was dependent on the local baseline diameter, the local ILT thickness, and for wall segments not covered by ILT, also on the local wall stress level (all p<0.001). For wall segments that were covered by a thick ILT layer, wall stress did not affect the growth rate (p=0.08). CONCLUSION: Diameter is not only a strong global predictor but also a local predictor of aneurysm growth. In addition, and independent of the diameter, the ILT thickness and wall stress (for the ILT-free wall) also influence the local growth rate. The high stress sensitivity of nondilated aortic walls suggests that wall stress peaks could initiate AAA formation. In contrast, local diameters and ILT thicknesses determine AAA growth for dilated and ILT-covered aortic walls. PMID- 27412647 TI - The Journal for Psychoses and Related Disorders. PMID- 27412648 TI - Engaging Research Domain Criteria (RDoC): Neurocircuitry in Search of Meaning. AB - The Research Domain Criteria (RDoC) initiative was implemented to reorient the approach to mental health research from one focused on Diagnostic and Statistical Manual of Mental Disorders (DSM) nosology to one oriented to psychological constructs constrained by neurocircuitry and molecular entities. The initiative has generated significant discussion and valuable reflection on the moorings of psychiatric research. The purpose of this article is to illustrate how a basic or clinical investigator can engage RDoC to explore the neurobiological underpinnings of psychopathology and how a research question can be formulated in RDoC's framework. We utilize a brain region with significant growing interest, the habenula, as an example for probing RDoC's utility. Opportunities to enhance neurocircuitry-psychological construct associations and problems associated with neuronal populations that enable bidirectional circuitry influence are discussed. The exercise reveals areas for further development that could move RDoC from a promising research idea to a successfully engaged foundation for catalyzing clinically relevant discoveries. PMID- 27412649 TI - Toward the Rational Design of Galactosylated Glycoclusters That Target Pseudomonas aeruginosa Lectin A (LecA): Influence of Linker Arms That Lead to Low Nanomolar Multivalent Ligands. AB - Anti-infectious strategies against pathogen infections can be achieved through antiadhesive strategies by using multivalent ligands of bacterial virulence factors. LecA and LecB are lectins of Pseudomonas aeruginosa implicated in biofilm formation. A series of 27 LecA-targeting glycoclusters have been synthesized. Nine aromatic galactose aglycons were investigated with three different linker arms that connect the central mannopyranoside core. A low nanomolar (Kd =19 nm, microarray) ligand with a tyrosine-based linker arm could be identified in a structure-activity relationship study. Molecular modeling of the glycoclusters bound to the lectin tetramer was also used to rationalize the binding properties observed. PMID- 27412650 TI - Patient Education Competence Scale for Registered Nurses in Taiwan: Scale development and psychometric validation. AB - AIM: To develop a valid and reliable self-assessment scale that can be used by registered nurses in Taiwan to completely measure their patient education competence. METHODS: The Patient Education Competence Scale for Registered Nurses was developed by using expert reviews, item analysis, exploratory factor analysis, criterion validity, and internal consistency and stability to test the construct validity and instrument stability. RESULTS: The exploratory factor analysis of the Patient Education Competence Scale for Registered Nurses from 133 responses revealed 24 items loading on two factors: implementation of patient education and preparation for patient education. The Patient Education Competence Scale for Registered Nurses correlated positively with the Clinical Teaching Competence Inventory. The Cronbach's alpha ranged from 0.96 to 0.97 and the test retest reliability ranged from 0.82 to 0.88. CONCLUSION: The construct validity and internal consistency reliability of the Patient Education Competence Scale for Registered Nurses were supported. This scale reflected the characteristics of Taiwan's clinical nursing practice and it may be used to assess current patient education competence practice and the need for continuing education and study. However, additional research is needed to refine this scale and increase the possibility of generalizability. PMID- 27412651 TI - Functional synergy of anti-mir221 and nanohydroxyapatite scaffold in bone tissue engineering of rat skull. AB - An appropriate cell source, effective cell modification, and proper supportive matrices are the main bases of tissue engineering. The effectiveness of anti mir221 or hydroxyapatite (HA) in improving the osteogenic differentiation of mesenchymal stem cells (MSCs) has been reported previously. Herein, simultaneous application of these osteogenic inducers was investigated in vivo. The Poly caprolactone (PCL)/HA nanofibers were characterized using contact angle measurement, tensile test, Fourier transform infrared spectroscopy, and electron microscopy. Rat MSCs were isolated, characterized and transfected with anti mir221. The rats were divided into 4 groups and an 8 mm defect were created in the mid-calvaria of each rat by trephine bur. Group 1 received (PCL)/HA nanofibers, group 2 received (PCL)/HA nanofibers plus autologous MSCs, group 3 received (PCL)/HA nanofibers plus MSCs transfected with anti-mir221, and group 4 rats were left empty as an additional control group. Histomorphometric and radiomorphometric evaluation after 4 and 8 weeks revealed more new bone formation in the cell-treated groups compared to the scaffold alone group. There was evidence for a combination of increased osteoclasts and osteoblast vascular lake containing red blood cells in the anti-mir221 transfected group. New bone penetration into the scaffolds empirically demonstrated the capability of this combination for efficient osteointegration. Altogether, the co-application of HA and anti-mir221 transfected cells can enhance bone healing of the rat skull. PMID- 27412652 TI - Synergistic effects of bioactive ions and micro/nano-topography on the attachment, proliferation and differentiation of murine osteoblasts (MC3T3). AB - Surface topography and chemical nature of biological materials play an important role in regulating cell behaviors. For the intention of improving the biological performance of Ti6Al4V, the hierarchical micro/nano-topographies containing bioactive ions (Ca(2+) and Mg(2+)) were fabricated in this study. Briefly, the hierarchical micro/nano-topography was constructed on Ti6Al4V surface via sandblasting, acid etching and alkali-hydrothermal treatment. Then Na(+) existing in the nano-topography was replaced by Ca(2+) and Mg(2+) through hydrothermal reaction. The surface topographies and chemical nature of native and treated samples were characterized using laser scanning microscope, X-ray Photoelectron Spectroscopy and field emission scanning electron microscopy with the energy dispersive spectroscopy. Surface wettability was measured with a contact angle goniometer. A series of biological tests were carried out to evaluate the synergistic effects of bioactive ions and micro/nano-topography on the attachment, proliferation and differentiation of murine osteoblastic MC3T3 cells. The results of in vitro tests indicated that Ca(2+) and Mg(2+) in the titanium alloy surface had an affirmative effect on cells attachment, proliferation and differentiation. Cells grown onto micro/nano-structured surface with Ca(2+) implantation exhibited significantly higher differentiation levels of alkaline phosphatase activity and mineralization compared to that on micro/nano-structured surface with Mg(2+) implantation. This study provided a novel method to construct a favorable biological environment between tissues and implants. PMID- 27412653 TI - Attenuated total reflection fourier transform infrared spectroscopy towards disclosing mechanism of bacterial adhesion on thermally stabilized titanium nano interfaces. AB - Titanium is widely used as medical implant material and as condenser material in the nuclear industry where its integrity is questioned due to its susceptibility to bacterial adhesion. A systematic investigation on the influence of thermally (50-800 degrees C) stabilized titanium (TS-Ti) nano oxide towards bacterial adhesion was carried out. The results showed that below 350 degrees C significant bacterio-phobicity was observed, while above 500 degrees C significant affinity towards bacterial cells was recorded. Conventional characterization tools such as HR-TEM and XRD did not provide much insight on the changes occurring on the oxide film with heat treatment, however, attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) of the surface showed significant changes in the spectral pattern as a function of increasing heat treatment. It was observed that elevated OH, N-H and C=O groups and rutile titania on the TS-Ti oxide films led to higher affinity for bacterial adhesion. On the other hand low temperature TS-Ti nanooxide films (<350 degrees C) showed high C-H groups and decreased OH groups on their surface, which possibly contributed towards their bacterio-phobicity. The TS-Ti nanooxide film grown at 50 degrees C was observed to be the most efficient anti-bacterial adhesion interface, while the 800 degrees C interface was the one showing highest affinity towards bacterial adhesion. This study confirms the successful application of ATR-FTIR technique for nano-oxide film characterization and towards understanding the variations in bacterial interaction of such nano interfaces. PMID- 27412654 TI - Does metabolic health in overweight and obesity persist? - Individual variation and cardiovascular mortality over two decades. AB - OBJECTIVE: Overweight and obese individuals may be metabolically healthy, but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk. DESIGN: Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal-weight and overweight or obese males followed for 20years. METHODS: Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and sub-clinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated. RESULTS: There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA IR 2.63, 95% CI: 1.79-3.65, P<0.001) relative to normal-weight participants (median HOMA-IR 1.67, 95% CI: 1.08-2.67, P<0.001) as was sub-clinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight individuals (hazard ratio 1.13, 95% CI: 0.34-3.72, P=0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39% respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal-weight individuals (P=0.007), but proportions converged thereafter. CONCLUSIONS: Despite being insulin resistant and having greater sub-clinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal weight equivalents. PMID- 27412655 TI - Structure Dependence of Lysosomal Transit of Chitosan-Based Polyplexes for Gene Delivery. AB - Chitosan-based polyplexes are known to traffic through lysosomes for a relatively long time, independent of the degree of deacetylation (DDA) and the number average molecular weight (Mn) of the polymer, even though both of these parameters have profound effects on polyplex stability and transfection efficiency. A better understanding of the lysosomal barrier is paramount to the rational design of vectors capable of overcoming obstacles to transgene expression. The aim of the present study was to investigate if lysosomal transit affects chitosan-based polyplex transfection efficiency in a structure-dependent (DDA, Mn) manner. Toward this end, we analyzed the effects of intracellular trafficking modifying agents on transfection efficiency and intracellular vesicular trafficking of polyplexes with different structural properties and stabilities or nucleic acid binding affinity. The use of agents that modify endosome/lysosome acidification and transit processes by distinct mechanisms and their effect on cell viability, polyplex uptake, vesicular trafficking, and transfection efficiency revealed novel and strong chitosan structure-dependent consequences of lysosomal transit. Inhibiting lysosomal transit using chloroquine significantly increased the efficiency of unstable polyplexes, while having minimal effects for polyplexes with intermediate or high stability. In parallel, specifically inhibiting the acidification of vesicles abrogated transfection for all formulations, suggesting that vesicular acidification is essential to promote transfection, most probably by facilitating lysosomal escape. These results provide novel insights into the structure-performance relationship of chitosan based gene delivery systems. PMID- 27412657 TI - Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. AB - OBJECTIVES: To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. METHODS: Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM MSCs, 5g/cm(3) (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm(3) HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. RESULTS: Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. CONCLUSIONS: All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes.Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287-293. DOI: 10.1302/2046-3758.57.2000587. PMID- 27412658 TI - Left Atrial Volumes and Function by Three-Dimensional Echocardiography: Reference Values, Accuracy, Reproducibility, and Comparison With Two-Dimensional Echocardiographic Measurements. AB - BACKGROUND: Our study sought to (1) identify reference values for left atrial (LA) volumes and phasic function indices by 3-dimensional echocardiography (3DE) and compare them with those measured by 2-dimensional echocardiography (2DE) and (2) analyze their relationship with age, sex, body size, and left ventricular function. Accuracy and reproducibility of 3DE and 2DE have been also tested to evaluate the robustness of our data. METHODS AND RESULTS: We obtained maximal, minimal, and preA LA volumes by 3DE and 2DE in 276 healthy volunteers (18-79 years; 57% women). Limits of normality for LA volumes and total LA emptying fraction were larger with 3DE than with 2DE (maximal LA volume: 43 versus 35 mL/m(2); preA LA volume: 31 versus 25 mL/m(2); minimal LA volume: 18 versus 14 mL/m(2); 53 versus 48%, respectively; P<0.001). 3DE LA volumes indexed by body surface area were similar in men and women and increased with age. On multivariable analysis, age, weight, and left ventricular systolic and diastolic function indices resulted as correlates of LA 3DE indices. LA volumes were tightly correlated with cardiac magnetic resonance measurements, yet more underestimated by 2DE versus 3DE (bias+/-SD: -17+/-16 versus -7+/-15 mL, respectively). Among all LA parameters, maximal LA volume and total emptying fraction were the most reproducible, including at test-retest and at expert versus trainee comparisons. CONCLUSIONS: This study provides reference values for LA 3DE volumes and function from a relatively large cohort of healthy subjects with a wide age range. Our data may help clinicians to identify LA remodeling and dysfunction. PMID- 27412659 TI - Extent of Myocardium at Risk for Left Anterior Descending Artery, Right Coronary Artery, and Left Circumflex Artery Occlusion Depicted by Contrast-Enhanced Steady State Free Precession and T2-Weighted Short Tau Inversion Recovery Magnetic Resonance Imaging. AB - BACKGROUND: Contrast-enhanced steady state free precession (CE-SSFP) and T2 weighted short tau inversion recovery (T2-STIR) have been clinically validated to estimate myocardium at risk (MaR) by cardiovascular magnetic resonance while using myocardial perfusion single-photon emission computed tomography as reference standard. Myocardial perfusion single-photon emission computed tomography has been used to describe the coronary perfusion territories during myocardial ischemia. Compared with myocardial perfusion single-photon emission computed tomography, cardiovascular magnetic resonance offers superior image quality and practical advantages. Therefore, the aim was to describe the main coronary perfusion territories using CE-SSFP and T2-STIR cardiovascular magnetic resonance data in patients after acute ST-segment-elevation myocardial infarction. METHODS AND RESULTS: CE-SSFP and T2-STIR data from 2 recent multicenter trials, CHILL-MI and MITOCARE (n=215), were used to assess MaR. Angiography was used to determine culprit vessel. Of 215 patients, 39% had left anterior descending artery occlusion, 49% had right coronary artery occlusion, and 12% had left circumflex artery occlusion. Mean extent of MaR using CE-SSFP was 44+/-10% for left anterior descending artery, 31+/-7% for right coronary artery, and 30+/-9% for left circumflex artery. Using T2-STIR, MaR was 44+/-9% for left anterior descending artery, 30+/-8% for right coronary artery, and 30+/ 12% for left circumflex artery. MaR was visualized in polar plots, and expected overlap was found between right coronary artery and left circumflex artery. Detailed regional data are presented for use in software algorithms as a priori information on the extent of MaR. CONCLUSIONS: For the first time, cardiovascular magnetic resonance has been used to show the main coronary perfusion territories using CE-SSFP and T2-STIR. The good agreement between CE-SSFP and T2-STIR from this study and myocardial perfusion single-photon emission computed tomography from previous studies indicates that these 3 methods depict MaR accurately in individual patients and at a group level. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01379261 and NCT01374321. PMID- 27412660 TI - Advances in Magnetic Resonance Imaging of the Myocardial Area at Risk and Salvage. PMID- 27412661 TI - Complexities of Left Atrial Analysis: More Than Meets the Eye? PMID- 27412662 TI - Temporal prediction modulates the evaluative processing of "good" action feedback: An electrophysiological study. AB - The present study aimed to investigate whether or not the evaluative processing of action feedback can be modulated by temporal prediction. For this purpose, we examined the effects of the predictability of the timing of action feedback on an ERP effect that indexed the evaluative processing of action feedback, that is, an ERP effect that has been interpreted as a feedback-related negativity (FRN) elicited by "bad" action feedback or a reward positivity (RewP) elicited by "good" action feedback. In two types of experimental blocks, the participants performed a gambling task in which they chose one of two cards and received an action feedback that indicated monetary gain or loss. In fixed blocks, the time interval between the participant's choice and the onset of the action feedback was fixed at 0, 500, or 1,000 ms in separate blocks; thus, the timing of action feedback was predictable. In mixed blocks, the time interval was randomly chosen from the same three intervals with equal probability; thus, the timing was less predictable. The results showed that the FRN/RewP was smaller in mixed than fixed blocks for the 0-ms interval trial, whereas there was no difference between the two block types for the 500-ms and 1,000-ms interval trials. Interestingly, the smaller FRN/RewP was due to the modulation of gain ERPs rather than loss ERPs. These results suggest that temporal prediction can modulate the evaluative processing of action feedback, and particularly good feedback, such as that which indicates monetary gain. PMID- 27412663 TI - [Hypercholesterolemia - Where are we today? Where are we going?]. AB - Hypercholesterolemia is one of the major modifiable risk factors for the development of atherosclerosis. Increasing LDL cholesterol is associated with an increased risk of developing cardiovascular diseases as well as cardiovascular ischemic complications. Studies with statins and ultimately with ezetimibe have been able to impressively demonstrate that lowering LDL cholesterol contributes to a significant reduction of cardiovascular ischemic complications.Based on the results of randomized trials for lipid lowering, the practice guidelines developed by the professional societies have defined LDL cholesterol goals. High risk patients, such as patients with clinically manifest cardiovascular disease, type 2 diabetes, type 1 diabetes with organ damage, moderate or severe chronic kidney disease or a risk of SCORE >=10 %, should reach LDL cholesterol values <70 mg/dl. Data from observational trials demonstrated that in daily practice only about 20 % of treated high-risk patients reached this recommended LDL cholesterol goal. The therapeutic options are not yet exhausted; patients are treated mainly with low or at most average statin dosages. There should be more potent and high dose statins used as well as the combination therapy of statin and ezetimibe to achieve the recommended LDL cholesterol goals. Specific cardiac rehabilitation and prevention programs with regular benchmarking could support improved goal achievement. The new therapeutic option of PCSK9 inhibitors, which significantly and safely lower LDL cholesterol on top of statins and ezetimibe, is currently investigated in large randomized outcome trials. PMID- 27412664 TI - [Assessment of subjective physical well-being in heart failure : Validation of the FEW16 questionnaire]. AB - INTRODUCTION: Improvement in the quality of life (QoL) is a major goal of therapy for heart failure (HF) patients. Physical well-being as an important component of QoL has not yet been sufficiently covered by disease-specific assessment instruments. The aim of the study was to validate the questionnaire for assessing subjective physical well-being (FEW16) in HF patients with preserved ejection fraction (HFpEF) from the exercise training in diastolic heart failure (Ex-DHF-P) trial. METHOD: A total of 64 HFpEF patients (65 years, 56 % female) were randomized to usual routine treatment with (n = 44) or without training (n = 20). At baseline and 3 months, patients were clinically evaluated and assessed using appropriate questionnaires on the QoL (SF36), physical well-being (FEW16) and depression (PHQ-D). RESULTS: The FEW16 showed good values for Cronbachs' alpha coefficients (0.85-0.93). The cross-validity with SF36 and PHQ-D was highly significant but more so for psychological aspects. At baseline, the FEW16 score correlated with age, the subscale resilience with age and the 6 min walking distance test. At follow-up, the total and resilience scores had improved in the training group. In contrast to the SF36, the FEW16 did not detect differences between the groups in Ex-DHF-P. DISCUSSION: The FEW16 questionnaire showed good internal consistency and correlation with SF36, its total score and resilience had improved after training; however, it did not reflect different changes between the study groups. The FEW16 is therefore more suited to assess general/mental well-being than the subjective physical well-being. PMID- 27412665 TI - On the heterogeneity of the femoral enthesis of the human ACL: microscopic anatomy and clinical implications. AB - BACKGROUND: Most ruptures of the native anterior cruciate ligament (ACL) and ACL graft occur at, or near, the femoral enthesis, with the posterolateral fibers of the native ligament being especially vulnerable during pivot landings. Characterizing the anatomy of the ACL femoral enthesis may help us explain injury patterns which, in turn, could help guide injury prevention efforts. It may also lead to improved anatomic reconstruction techniques given that the goal of such techniques is to replicate the knee's normal anatomy. Hence, the aim of this study was to investigate the microscopic anatomy of the ACL femoral enthesis and determine whether regional differences exist. METHODS: Fifteen human ACL femoral entheses were histochemically processed and sectioned along the longitudinal axis of the ACL at 20, 40, 60, and 80 % of the width of the enthesis. Four thick sections (100 MUm) per enthesis were prepared, stained, and digitized. From these sections, regional variations in the quantity of calcified and uncalcified fibrocartilage, the angle at which the ligament originates from the bone, and the shape profile of the tidemark were quantified. RESULTS: At least 33 % more calcified fibrocartilage and 143 % more uncalcified fibrocartilage were found in the antero-inferior region, which corresponds to the inferior margin of the origin of the anteromedial ACL fibers, than all other regions (Ps < 0.05). In addition, the anteromedial fibers of the ACL originated from the femur at an angle six times greater than did its posterolateral fibers (P = 0.032). Finally, average entheseal tidemark profiles correlated bilaterally (Pearson's r = 0.79; P = 0.036), the most common profile being convex with a single re-entrant. CONCLUSIONS: Systematic regional differences were found in fibrocartilage quantity and collagen fiber attachment angles. The marked differences may reflect differences in the loading history of the various regions of the ACL femoral enthesis. These differences, which could affect the potential for injury, should also be considered when developing new ACL reconstruction approaches. PMID- 27412666 TI - [Autoinflammatory syndromes : Practical approach to diagnostics and therapy]. PMID- 27412667 TI - [Glucocorticoids]. PMID- 27412669 TI - Nasal administration of leptin dose-dependently increases dopamine and serotonin outflow in the rat nucleus accumbens. AB - Leptin is an anorexigenic hormone that acts via its receptor (LepR) to regulate the hypothalamic arcuate nucleus circuitry to mediate energy homeostasis and feeding behavior. Moreover, leptin decreases the reward value of natural and artificial rewards, and low levels of circulating leptin have been implicated in several mood disorders linking leptin to the mesolimbic system. Therefore, the purpose of this study was to assess whether and to what extent an acute intranasal application of leptin is able to modulate monoamine neurotransmitters in the nucleus accumbens (NAc). Microdialysis experiments were carried out in freely moving Wistar rats and in LepR-deficient Zucker rats (LepRfa/fa). Samples were analysed for the levels of dopamine (DA), serotonin (5-HT), and their metabolites using high-performance liquid chromatography with electrochemical detection. We show that in Wistar rats, nasal application of leptin dose dependently increased extracellular DA and 5-HT levels in the NAc. By contrast, in the LepRfa/fa rats, nasal application of 0.12 mg/kg leptin failed to increase levels of either DA or 5-HT, but their metabolites (DOPAC and HIAA, respectively) were significantly decreased. In addition, leptin interaction with the melanocortin system was tested. Nasal co-administration of leptin and the melanocortin receptor antagonist, SHU9119, completely abolished the leptin induced increase of both DA and 5-HT outflow in the NAc. These results indicate a marked leptin effect on the basal ganglia-related reward system involving melanocortin receptors. PMID- 27412670 TI - Effect of Interventional Program on the Utilization of PACS in Point-of-Care Ultrasound. AB - While the implementation of Picture Archiving and Communication Systems (PACS) has revolutionized the field of radiology, there has been considerably less utilization of PACS by emergency physicians with point-of-care ultrasound. Benefits of PACS archival of images include improved quality assurance, preservation of image quality, and accessibility of images. Our objective was to determine if a simple interventional program would influence the utilization of PACS in point-of-care ultrasound. A before-after study was conducted in an urban, academic emergency department. Data was collected during a 4-week baseline period, a 12-week intervention period, and a 12-week post-intervention period. The percentage of ultrasound studies archived to PACS was recorded during each week of the study. Interventions were designed to encourage the utilization of PACS. A significant increase in the mean percentage of PACS studies was found between the baseline and intervention period (59.4 %; 95 % CI: 34.76-84.08 %; p < 0.001). Mean percentage of PACS studies at 1-month (74.3 %), 2-month (61.0 %), and 3-month (74.8 %) post-intervention periods remained elevated and were all significantly increased compared to baseline values (p < 0.001). Mean percentages of PACS studies at 1-month, 2-month, and 3-month post-intervention periods were not statistically significant from the intervention period (p = 0.977, p = 0.849, p = 0.967, respectively). A simple interventional program for emergency physicians can significantly increase and sustain the utilization of PACS for point-of-care ultrasound. PMID- 27412671 TI - Laparoscopic Adjustable Gastric Banding After Failed Roux-En-Y Gastric Bypass. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is associated with approximately 25 % weight loss failure, resulting in insufficient weight loss or weight regain. Strategies of revisional surgery focus on alteration of limb length, pouch or stoma size. Altering pouch size and outlet by adding laparoscopic adjustable gastric band (LAGB) might initiate further weight loss. The goal of this study is to review the safety and efficacy of LAGB after failed RYGB in a retrospective cohort of patients in our institute. METHODS: Patients with secondary LAGB (n = 44) were studied between May 2012 and January 2015. Demographics, effects on weight loss and complications were analysed. RESULTS: Mean age and body mass index (BMI) at time of LAGB was 45.8 +/- 8.2 years and 37.2 +/- 5.4 kg/m2, respectively. Mean interval between RYGB and LAGB was 2.6 +/- 1.3 years. Mean follow-up was 14 +/- 7.9 months, with 25 % loss to follow-up at 12 months. Due to LAGB, patients lost an additional 17.6 % +/- 28.3 % excess weight. Patients with weight regain after initial weight loss success showed more excess weight loss (EWL) compared to patients whom never reached 50% EWL after RYGB. Overall complication and reoperation rates were 30 and 21 %, respectively, with 16 % band removal. One fatality due to septic shock following band erosion was observed. CONCLUSION: In this largest published cohort, secondary banding of failed RYGB provides only limited additional weight loss. Furthermore, this technique is associated with high morbidity and reoperation rates. A significant difference in effect was found between patients with weight loss failure and weight regain. Larger prospective series are necessary to evaluate if the modest benefits are worth the risks of secondary LAGB. PMID- 27412672 TI - Comment on "Shorten than 24-h Hospital Stay for Sleeve Gastrectomy Is Safe and Feasible". PMID- 27412674 TI - Clavibacter michiganensis subsp. capsici subsp. nov., causing bacterial canker disease in pepper. AB - Clavibacter michiganensis is a Gram-stain-positive bacterium with eight subspecies. One of these subspecies is C. michiganensis subsp. michiganensis, which causes bacterial canker disease in tomato. Bacterial strains showing very similar canker disease symptoms to those of a strain originally classified as C. michiganensis have been isolated from pepper. In this paper, we reclassified strains isolated from pepper. On the basis of phylogenetic analysis with 16S rRNA gene sequences, the strains isolated from pepper were grouped in a separate clade from other subspecies of C. michiganensis. Biochemical, physiological and genetic characteristics of strain PF008T, which is the representative strain of the isolates from pepper, were examined in this study. Based on multi-locus sequence typing and other biochemical and physiological features including colony color, utilization of carbon sources and enzyme activities, strain PF008T was categorically differentiated from eight subspecies of C. michiganensis. Moreover, genome analysis showed that the DNA G+C content of strain PF008T is 73.2 %. These results indicate that PF008T is distinct from other known subspecies of C. michiganensis. Therefore, we propose a novel subspecies, C. michiganensis subsp. capsici, causing bacterial canker disease in pepper, with a type strain of PF008T (=KACC 18448T=LMG 29047T). PMID- 27412675 TI - Synthesis of a novel photoactivatable glucosylceramide cross-linker. AB - The biosynthesis of glucosylceramide (GlcCer) is a key rate-limiting step in complex glycosphingolipid (GSL) biosynthesis. To further define interacting partners of GlcCer, we have made a cleavable, biotinylated, photoreactive GlcCer analog in which the reactive nitrene is closely apposed to the GlcCer head group, by substituting the native fatty acid with d, l-2-aminohexadecanoic acid. Two amino-GlcCer diastereomer cross-linkers (XLA and XLB) were generated. XLB proved an effective lactosylceramide (LacCer) synthase substrate while XLA was inhibitory. Both probes specifically bound and cross-linked the GlcCer binding protein, glycolipid transfer protein (GLTP), but not other GSL binding proteins (Shiga toxin and cholera toxin). GlcCer inhibited GLTP cross-linking. Both GlcCer cross-linkers competed with microsomal nitrobenzoxadiazole (NBD)-GlcCer anabolism to NBD-LacCer. GLTP showed marked, ATP-dependent enhancement of cell-free intact microsomal LacCer synthesis from endogenous or exogenous liposomal GlcCer, supporting a role in the transport/membrane translocation of cytosolic and extra Golgi GlcCer. GLTP was specifically labeled by either XLA or XLB GlcCer cross linker during this process, together with a (the same) small subset of microsomal proteins. These cross-linkers will serve to probe physiologically relevant GlcCer interacting cellular proteins. PMID- 27412676 TI - Multidimensional regulation of lipoprotein lipase: impact on biochemical and cardiovascular phenotypes. PMID- 27412677 TI - Role of Mesenchymal Stem Cells in Dermal Repair in Burns and Diabetic Wounds. AB - In this review we explore stem cell function in wounds that are resistant to healing, such as burn injuries and diabetic wounds. Diabetic ulcers are of interest due to their remarkable resistance to heal; severe thermal burns are addressed due to critical need for effective therapies for the prevention shock and improvement in scarring. Cell-based therapy utilizing mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, are currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe thermal burns. The clinical utility of stem cells, in particular MSCs, in caring for these types of injuries is primarily based on repairing and replacing cellular substrates, attenuation of inflammation, increasing angiogenesis, and enhancing migration of reparative cells. MSCs are sought after due to their unique ability to initiate different wound-healing programs, depending on the environmental milieu. Thus, this review aims to highlight the properties of MSCs, including their characterization, immunogenicity, and function in the context of dermal repair and regeneration in severe burns and diabetic wounds. Additionally, relevant clinical and pre-clinical studies illustrating the impact of allogeneic and autologous sources of MSCs on therapeutic efficacy are reviewed. Insight into the properties of MSCs and the dramatic host-to-MSC interactions within these pathological states may lead to the development of effective strategies for improving outcomes in impaired wounds. PMID- 27412678 TI - Hospital Exemption for Advanced Therapy Medicinal Products: Issue in Application in the European Union Member States. AB - Regulation (EC) 1394/2007 of the European Parliament and the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 allowed the use of non - authorized advanced therapy medicinal products under the certain circumstances. This socalled hospital exemption rule needs to be applied in the each Member State of the European Union individually and for this purpose Member States should provide national procedures and control measures. The aim of this article is to clear up the criteria for hospital exemption listed in Regulation (EC) 1394/2007 and to contrast the difference in implementing hospital exemption rule into national legal regimes on examples of the United Kingdom, Lithuania and Poland. PMID- 27412679 TI - Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes. AB - PURPOSE: Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. METHODS: Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter <=25.5 nm). RESULTS: Renal patients with LDL A phenotype had increased oxidative stress (TOS: p < 0.01, and TBARS: p < 0.001) and decreased total SH- groups (p < 0.001) compared to controls with the same LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p < 0.001) and LDL B phenotype (p < 0.05) compared with appropriate controls. LDL B phenotype was characterized with increased TBARS (p < 0.05) compared with LDL A phenotype in control group. CONCLUSION: Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype. PMID- 27412680 TI - Amphiphilic Phospholipid-Based Riboflavin Derivatives for Tumor Targeting Nanomedicines. AB - Riboflavin (RF) is an essential vitamin for cellular metabolism. Recent studies have shown that RF is internalized through RF transporters, which are highly overexpressed by prostate and breast cancer cells, as well as by angiogenic endothelium. Here, we present an optimized synthesis protocol for preparing tailor-made amphiphilic phospholipid-based RF derivatives using phosphoramidite chemistry. The prepared RF amphiphile-RfdiC14-can be inserted into liposome formulations for targeted drug delivery. The obtained liposomes had a hydrodynamic size of 115 +/- 5 nm with narrow size distribution (PDI 0.06) and a zeta potential of -52 +/- 3 mV. In vitro uptake studies showed that RfdiC14 containing liposomes were strongly internalized in HUVEC, PC3, and A431 cells, in a specific and transporter-mediated manner. To assess the RF targeting potential in vivo, an amphiphile containing PEG spacer between RF and a lipid was prepared DSPE-PEG-RF. The latter was successfully incorporated into long-circulating near infrared-labeled liposomes (141 +/- 1 nm in diameter, PDI 0.07, zeta potential of -33 +/- 1 mV). The longitudinal MUCT/FMT biodistribution studies in PC3 xenograft bearing mice demonstrated similar pharmacokinetics profile of DSPE-PEG-RF functionalized liposomes compared to control. The subsequent histological evaluation of resected tumors revealed higher degree of tumor retention as well as colocalization of targeted liposomes with endothelial cells emphasizing the targeting potential of RF amphiphiles and their utility for the lipid-containing drug delivery systems. PMID- 27412673 TI - Indications for Surgery for Obesity and Weight-Related Diseases: Position Statements from the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). PMID- 27412681 TI - Zika virus as a causative agent for primary microencephaly: the evidence so far. AB - Zika virus (ZIKV) infection has been associated with congenital microcephaly and peripheral neuropathy. The ongoing epidemic has triggered swift responses in the scientific community, and a number of recent reports have now confirmed a causal relationship between ZIKV infection and birth defect. In particular, ZIKV has been shown to be capable of compromising and crossing the placental barrier and infect the developing fetal brain, resulting in the demise and functional impairment of neuroprogenitor cells critical for fetal cortex development. Here, the evidence for ZIKV as a teratogenic agent that causes microcephaly is reviewed, and its association with other disorders is discussed. PMID- 27412683 TI - Exposure to young preferentially activates adult-born neurons in the main olfactory bulb of sheep mothers. AB - New neurons are continuously added to the main olfactory bulb (MOB) of the mammalian brain. While their function has been demonstrated in olfactory learning, it is less known in an ethological context such as mothering. We addressed this question by investigating whether in sheep mothers the adult generated olfactory neurons contribute to the processing of odors involved in attraction to lambs and in memorization of its individual signature. Parturient ewes, after having 2 days of contact with their lamb and being separated from them for 3 h, were exposed for 2 h either to their own lamb, an unfamiliar lamb or a familiar adult sheep and then sacrificed. A control group was composed of mothers not exposed to any lambs for 5 h before sacrifice. Bromodeoxyuridine, a marker of cell division, was injected 3 months before parturition and revealed through immunocytochemistry in combination with markers of activation or neuronal maturation. The percentage of adult-born cells activated in the granular layer of the MOB was compared between the four groups. Results show that the whole population of olfactory neuroblasts and in particular the 3-month-old neuroblasts, are preferentially activated by lamb exposure and that the preferential activation is specific to olfactory neurogenesis since no activation was observed in newborn neurons of the dentate gyrus. However, neither neuroblasts nor mature neurons of the MOB differentiate between familiar and unfamiliar lamb exposure. Therefore, our data shows that adult-born neurons contribute to the processing of infantile odors which are determinant for maternal behavior. PMID- 27412684 TI - Neurological Complications of Ebola Virus Infection. AB - Ebola virus disease is one of the deadliest pathogens known to man, with a mortality rate between 25-90% depending on the species and outbreak of Ebola. Typically, it presents with fever, headache, voluminous vomiting and diarrhea, and can progress to a hemorrhagic illness; neurologic symptoms, including meningoencephalitis, seizures, and coma, can also occur. Recently, an outbreak occurred in West Africa, affecting > 28,000 people, and killing > 11,000. Owing to the magnitude of this outbreak, and the large number (>17,000) of Ebola survivors, the medical and scientific communities are learning much more about the acute manifestations and sequelae of Ebola. A number of neurologic complications can occur after Ebola, such as seizures, memory loss, headaches, cranial nerve abnormalities, and tremor. Ebola may also persist in some immunologically privileged sites, including the central nervous system, and can rarely lead to relapse in disease. Owing to these findings, it is important that survivors are evaluated and monitored for neurologic symptoms. Much is unknown about this disease, and treatment remains largely supportive; however, with ongoing clinical and basic science, the mechanisms of how Ebola affects the central nervous system and how it persists after acute disease will hopefully become more clear, and better treatments and clinical practices for Ebola patients will be developed. PMID- 27412682 TI - The functional logic of corticostriatal connections. AB - Unidirectional connections from the cortex to the matrix of the corpus striatum initiate the cortico-basal ganglia (BG)-thalamocortical loop, thought to be important in momentary action selection and in longer-term fine tuning of behavioural repertoire; a discrete set of striatal compartments, striosomes, has the complementary role of registering or anticipating reward that shapes corticostriatal plasticity. Re-entrant signals traversing the cortico-BG loop impact predominantly frontal cortices, conveyed through topographically ordered output channels; by contrast, striatal input signals originate from a far broader span of cortex, and are far more divergent in their termination. The term 'disclosed loop' is introduced to describe this organisation: a closed circuit that is open to outside influence at the initial stage of cortical input. The closed circuit component of corticostriatal afferents is newly dubbed 'operative', as it is proposed to establish the bid for action selection on the part of an incipient cortical action plan; the broader set of converging corticostriatal afferents is described as contextual. A corollary of this proposal is that every unit of the striatal volume, including the long, C-shaped tail of the caudate nucleus, should receive a mandatory component of operative input, and hence include at least one area of BG-recipient cortex amongst the sources of its corticostriatal afferents. Individual operative afferents contact twin classes of GABAergic striatal projection neuron (SPN), distinguished by their neurochemical character, and onward circuitry. This is the basis of the classic direct and indirect pathway model of the cortico-BG loop. Each pathway utilises a serial chain of inhibition, with two such links, or three, providing positive and negative feedback, respectively. Operative co-activation of direct and indirect SPNs is, therefore, pictured to simultaneously promote action, and to restrain it. The balance of this rival activity is determined by the contextual inputs, which summarise the external and internal sensory environment, and the state of ongoing behavioural priorities. Notably, the distributed sources of contextual convergence upon a striatal locus mirror the transcortical network harnessed by the origin of the operative input to that locus, thereby capturing a similar set of contingencies relevant to determining action. The disclosed loop formulation of corticostriatal and subsequent BG loop circuitry, as advanced here, refines the operating rationale of the classic model and allows the integration of more recent anatomical and physiological data, some of which can appear at variance with the classic model. Equally, it provides a lucid functional context for continuing cellular studies of SPN biophysics and mechanisms of synaptic plasticity. PMID- 27412686 TI - Fluorescent lifetime imaging microscopy using Europium complexes improves atherosclerotic plaques discrimination. AB - The objective of this study is to characterize arterial tissue with and without atherosclerosis by fluorescence lifetime imaging microscopy (FLIM) using Europium Chlortetracycline complex (EuCTc) as fluorescent marker. For this study, twelve rabbits were randomly divided into a control group (CG) and an experimental group (EG), where they were fed a normal and hypercholesterolemic diet, respectively, and were treated for 60 days. Cryosections of the aortic arch specimens were cut in a vertical plane, mounted on glass slides, and stained with Europium (Eu), Chlortetracycline (CTc), Europium Chlortetracycline (EuCTc), and Europium Chlortetracycline Magnesium (EuCTcMg) solutions. FLIM images were obtained with excitation at 405 nm. The average autofluorescence lifetime within plaque depositions was ~1.36 ns. Reduced plaque autofluorescence lifetimes of 0.23 and 0.31 ns were observed on incubation with EuCTc and EuCTcMg respectively. It was observed a quenching of collagen, cholesterol and TG emission spectra increasing EuCTc concentration. The drastic reduction in fluorescence lifetimes is due to a resonant energy transfer between collagen, triglycerides, cholesterol and europium complexes, quenching fluorescence. PMID- 27412687 TI - Fracture resistance of implant-supported screw-retained zirconia-based molar restorations. AB - OBJECTIVES: The objective of this in vitro study was to investigate fracture loads of screw-retained zirconia-based molar restorations (hybrid abutment crown) fabricated with different restorative materials and designs. MATERIAL AND METHODS: Forty-four screw-retained zirconia-based molar restorations were fabricated on dental implants and divided into four groups (n = 11): porcelain layered zirconia-based restorations (PLZ), indirect composite-layered zirconia based restorations (ILZ), metal-ceramic restorations (MC), and monolithic zirconia restorations (MONO). The zirconia-based restorations in the PLZ, ILZ, and MONO groups were adhesively bonded on implant abutments with a dual polymerized resin material. All restorations were tightened on implant bodies with titanium screws and were tested for fracture resistance. The Kruskal-Wallis test and Steel-Dwass test were used to evaluate differences in fracture loads (alpha = 0.05). RESULTS: As compared with the other groups, the MONO specimens had a significantly higher mean fracture resistance (7.54 kN); no significant differences were found among the PLZ (1.96 kN), ILZ (1.80 kN), and MC (1.45 kN) groups (P > 0.05). For the PLZ, ILZ, and MC groups, all specimens fractured within the layering materials. In contrast, the fracture mode for the MONO group was complete fracture of the restorations. CONCLUSIONS: All restorations withstood the masticatory forces. Fracture loads were significantly higher for screw-retained implant-supported monolithic zirconia restorations than for screw retained bilayered restorations. For the screw-retained bilayered zirconia-based restorations, the fracture resistance of ILZ restorations was comparable to that of PLZ restorations and MC restorations. PMID- 27412685 TI - Clinical Trials of Immunomodulation in Ischemic Stroke. AB - Inflammatory mechanisms are currently considered as a prime target for stroke therapy. There is evidence from animal studies that immune signals and mediators can have both detrimental and beneficial effects in particular stages of the disease process. Moreover, several of these mechanisms are turned on with sufficient delay after ischemia onset to make them amenable to therapeutic intervention. Several clinical proof-of concept trials have investigated the efficacy of different immunomodulatory approaches in patients with stroke. Trials targeting the innate immune system have focused on reduction of microglial activation, inhibition of neutrophil migration, and interleukin-1 receptor blockade, suggesting that interleukin-1 receptor blockade may be a promising strategy. Studies aiming at halting T-cell migration have also been undertaken with controversial findings regarding prevention of infarct growth in neuroimaging studies. Consistently, recent proof-of-concept trials targeting lymphocytes with drugs such as natalizumab and fingolimod have yielded some promising results on clinical endpoints, but confirmation in larger trials is needed. At present, the understanding of the role of immune mechanisms in neurorepair and neurodegeneration is limited. Improving long-term brain function by mitigating prolonged neuroinflammation that was triggered by acute brain injury could be a strategy in addition to neuroprotection. PMID- 27412688 TI - Electrochemical detectors based on carbon and metallic nanostructures in capillary and microchip electrophoresis. AB - Carbon and metallic-based nanostructures have been progressively implemented as innovative electrochemical detectors in CE and microchip electrophoresis (ME). For both type of nanomaterials and toward selected examples, this review details the impact of these nanomaterials for enhanced detection performance in CE, ME, and paper-based microfluidic devices. The analytical performance and the analytical potential in real world applications is also presented and discussed. PMID- 27412689 TI - N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues. AB - Ovarian cancer is a fatal gynaecological malignancy in adult women with a five year overall survival rate of only 30%. Glycomic and glycoproteomic profiling studies have reported extensive protein glycosylation pattern alterations in ovarian cancer. Therefore, spatio-temporal investigation of these glycosylation changes may unearth tissue-specific changes that occur in the development and progression of ovarian cancer. A novel method for investigating tissue-specific N linked glycans is using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on formalin-fixed paraffin-embedded (FFPE) tissue sections that can spatially profile N-glycan compositions released from proteins in tissue-specific regions. In this study, tissue regions of interest (e.g. tumor, stroma, adipose tissue and necrotic areas) were isolated from FFPE tissue sections of advanced serous ovarian cancers (n = 3). PGC-LC-ESI-MS/MS and MALDI MSI were used as complementary techniques to firstly generate structural information on the tissue-specific glycans in order to then obtain high resolution images of the glycan structure distribution in ovarian cancer tissue. The N-linked glycan repertoires carried by the proteins in these tissue regions were structurally characterized for the first time in FFPE ovarian cancer tissue regions, using enzymatic peptide-N-glycosidase F (PNGase F) release of N-glycans. The released glycans were analyzed by porous graphitized carbon liquid chromatography (PGC-LC) and collision induced electrospray negative mode MS fragmentation analysis. The N-glycan profiles identified by this analysis were then used to determine the location and distribution of each N-glycan on FFPE ovarian cancer sections that were treated with PNGase F using high resolution MALDI-MSI. A tissue-specific distribution of N-glycan structures identified particular regions of the ovarian cancer sections. For example, high mannose glycans were predominantly expressed in the tumor tissue region whereas complex/hybrid N-glycans were significantly abundant in the intervening stroma. Therefore, tumor and non-tumor tissue regions were clearly demarcated solely on their N-glycan structure distributions. PMID- 27412690 TI - Human Leukocyte Antigen (HLA) Peptides Derived from Tumor Antigens Induced by Inhibition of DNA Methylation for Development of Drug-facilitated Immunotherapy. AB - Treatment of cancer cells with anticancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor's gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anticancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (Decitabine) has limited antitumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. The proteomics and HLA peptidomics data are available via ProteomeXchange with identifier PXD003790 and the transcriptomics data are available via GEO with identifier GSE80137. PMID- 27412691 TI - Simultaneous or sequential gastrectomy in pediatric liver transplant recipients. AB - The association between LT and gastrectomy is not common. Only two studies reported the gastrectomy/LT association in children. Here, we report three children who underwent LT who required a concomitant or sequential gastrectomy for different reasons. Patient 1, a 16-yr-old boy, during the LT, underwent a partial gastrectomy due to extensive injury to the duodenum. He had a previous and unusual portoenterostomy performed in the duodenum. Bowel reconstruction was performed using an intestinal loop that was first used for the bilio-enteric anastomosis and then connected to the gastric stump. Patient 2, a 22-month-old female child, underwent a partial gastrectomy with a Roux-en-Y reconstruction during a retransplantation. She had a large perforated gastric ulcer blocked by the allograft liver. Patient 3, a 26-month-old male child, five yr after living donor LT, was submitted to a partial gastrectomy because of gastric outlet obstruction. The histopathology was compatible with eosinophilic gastritis. The association between LT and gastrectomy in the pediatric population is extremely rare. Appropriate knowledge of the previous transplantation technique is very important. Further studies are required to assess the outcomes of the different types of gastric reconstruction in pediatric recipients. PMID- 27412692 TI - Convergence to consensus in heterogeneous groups and the emergence of informal leadership. AB - When group cohesion is essential, groups must have efficient strategies in place for consensus decision-making. Recent theoretical work suggests that shared decision-making is often the most efficient way for dealing with both information uncertainty and individual variation in preferences. However, some animal and most human groups make collective decisions through particular individuals, leaders, that have a disproportionate influence on group decision-making. To address this discrepancy between theory and data, we study a simple, but general, model that explicitly focuses on the dynamics of consensus building in groups composed by individuals who are heterogeneous in preferences, certain personality traits (agreeability and persuasiveness), reputation, and social networks. We show that within-group heterogeneity can significantly delay democratic consensus building as well as give rise to the emergence of informal leaders, i.e. individuals with a disproportionately large impact on group decisions. Our results thus imply strong benefits of leadership particularly when groups experience time pressure and significant conflict of interest between members (due to various between-individual differences). Overall, our models shed light on why leadership and decision-making hierarchies are widespread, especially in human groups. PMID- 27412693 TI - Fetal and neonatal maxillary ontogeny in extant humans and the utility of prenatal maxillary morphology in predicting ancestral affiliation. AB - OBJECTIVES: The midface of extant Homo sapiens is known to undergo shape changes through fetal and neo-natal ontogeny; however, little work has been done to quantify these shape changes. Further, while midfacial traits which vary in frequency between populations of extant humans are presumed to develop prenatally, patterns of population-specific variation maxillary shape across ontogeny are not well documented. Only one study of fetal ontogeny which included specific discussion of the midface has taken a three-dimensional geometric morphometric approach, and that study was limited to one population (Japanese). The present research project seeks to augment our understanding of fetal maxillary growth patterns, most especially in terms of intraspecific variation. MATERIALS AND METHODS: Three-dimensional coordinate landmark data were collected on the right maxillae of 102 fetal and neo-natal individuals from three groups (Euro-American, African-American, "Mixed Ancestry"). RESULTS: Shape changes were seen mainly in the lateral wall of the piriform aperture, the anterior nasal spine, and the subnasal alveolar region. The greatest difference across age groups (second trimester, third trimester, neonates) was between the second and third trimester. Euro-Americans and African-Americans clustered by population and differences in midfacial morphology related to ancestry could be discerned as early as the second trimester (p = .002), indicating that population variation in maxillary morphology appears very early in ontogeny. DISCUSSION: The midface is a critical region of the skull for assessing ancestry and these results indicate that maxillary morphology may be useful for estimating ancestry for prenatal individuals as young as the second trimester. PMID- 27412694 TI - Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 2. Label-free relative quantitative proteomics. AB - Mastitis, inflammation of the mammary gland, is the most common and costly disease of dairy cattle in the western world. It is primarily caused by bacteria, with Streptococcus uberis as one of the most prevalent causative agents. To characterize the proteome during Streptococcus uberis mastitis, an experimentally induced model of intramammary infection was used. Milk whey samples obtained from 6 cows at 6 time points were processed using label-free relative quantitative proteomics. This proteomic analysis complements clinical, bacteriological and immunological studies as well as peptidomic and metabolomic analysis of the same challenge model. A total of 2552 non-redundant bovine peptides were identified, and from these, 570 bovine proteins were quantified. Hierarchical cluster analysis and principal component analysis showed clear clustering of results by stage of infection, with similarities between pre-infection and resolution stages (0 and 312 h post challenge), early infection stages (36 and 42 h post challenge) and late infection stages (57 and 81 h post challenge). Ingenuity pathway analysis identified upregulation of acute phase protein pathways over the course of infection, with dominance of different acute phase proteins at different time points based on differential expression analysis. Antimicrobial peptides, notably cathelicidins and peptidoglycan recognition protein, were upregulated at all time points post challenge and peaked at 57 h, which coincided with 10 000-fold decrease in average bacterial counts. The integration of clinical, bacteriological, immunological and quantitative proteomics and other-omic data provides a more detailed systems level view of the host response to mastitis than has been achieved previously. PMID- 27412696 TI - HIV-1 Genetic Diversity and Drug Resistance Mutations Among Treatment-Naive Adult Patients in Suriname. AB - The molecular epidemiologic profile of HIV-1 in Suriname was determined through protease (PR) and reverse transcriptase (RT) sequences obtained from HIV-1 strains collected from 100 drug-naive HIV-1-infected persons. Subtype determination revealed that most viruses were of subtype B (94.9%) in both PR and RT genomic regions, followed by B/D recombinants (5.1%). Analysis of drug resistance mutations showed only one transmitted dug resistance mutation (TDRM) (V75M) in a single strain. The genetic data obtained can serve as a baseline for Suriname to monitor emerging mutations. This study reveals that the HIV-1 epidemic in Suriname is still characterized by a low TDRM rate (1%) and a low level of subtype diversity. However, both genes display a high genetic polymorphism. This high polymorphism may ultimately lead to drug resistance. Continuous monitoring of the baseline resistance is therefore a prerequisite to safeguard effective long-term treatment for people living with HIV-1 in Suriname. PMID- 27412695 TI - Letters to Addiction from Coffin et al. and Doe-Simpkins et al. re: 'For Debate' on clinical use of improvised nasal naloxone sprays: authors' response. PMID- 27412697 TI - Chirality specific and spatially uniform synthesis of single-walled carbon nanotubes from a sputtered Co-W bimetallic catalyst. AB - Synthesis of single-walled carbon nanotubes (SWNTs) with well-defined atomic arrangements has been widely recognized in the past few decades as the biggest challenge in the SWNT community, and has become a bottleneck for the application of SWNTs in nano-electronics. Here, we report a selective synthesis of (12, 6) SWNTs with an enrichment of 50%-70% by chemical vapor deposition (CVD) using sputtered Co-W as a catalyst. This is achieved under much milder reduction and growth conditions than those in the previous report using transition-metal molecule clusters as catalyst precursors (Nature, 2014, 510, 522). Meanwhile, in plane transmission electron microscopy unambiguously identified an intermediate structure of Co6W6C, which is strongly associated with selective growth. However, most of the W atoms disappear after a 5 min CVD growth, which implies that anchoring W may be important in this puzzling Co-W system. PMID- 27412698 TI - Growth status of children with autism spectrum disorder: a case-control study. AB - BACKGROUND: Children with autism spectrum disorder are at risk of a compromised dietary intake and nutritional status that could impact growth over both the short and long term. The limited body of published research addressing this concern has been contradictory and inconclusive to date. METHODS: This case control study investigated the height, weight, body mass index (BMI) and other anthropometric measurements of children diagnosed with autism spectrum disorder (ASD). Eighty-six children with ASD and 57 healthy controls participated in the study. Caregivers of participants who met the inclusion criteria completed a health history questionnaire, provided information on dietary intake and feeding behaviour, and completed a nutrition physical with a healthcare professional, which provided all of the anthropometric measurements required for the study. RESULTS: Body mass index and BMI Z-scores for females with ASD and corresponding healthy controls were significantly different. Female participants with ASD had significantly lower BMI and BMI Z-scores than control participants. The prevalence of risk for failure-to-thrive status was consistent across ASD subjects and controls. The prevalence of overweight and obesity was consistent across ASD subjects and controls. Children with ASD comprised 60% of the total number of children across BMI categories and mid-arm muscle circumference percentile ranges, which is consistent with the proportion of children in the overall sample. CONCLUSIONS: More research is needed to fully assess physical status and potential growth concerns of children with ASD. A full physical assessment should be a component of primary care for all children with ASD. PMID- 27412699 TI - Photo-induced enhanced Raman spectroscopy for universal ultra-trace detection of explosives, pollutants and biomolecules. AB - Surface-enhanced Raman spectroscopy is one of the most sensitive spectroscopic techniques available, with single-molecule detection possible on a range of noble metal substrates. It is widely used to detect molecules that have a strong Raman response at very low concentrations. Here we present photo-induced-enhanced Raman spectroscopy, where the combination of plasmonic nanoparticles with a photo activated substrate gives rise to large signal enhancement (an order of magnitude) for a wide range of small molecules, even those with a typically low Raman cross-section. We show that the induced chemical enhancement is due to increased electron density at the noble-metal nanoparticles, and demonstrate the universality of this system with explosives, biomolecules and organic dyes, at trace levels. Our substrates are also easy to fabricate, self-cleaning and reusable. PMID- 27412700 TI - Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation. AB - Recent studies have shown that tissue macrophages (MPhi) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize tissues before birth. Further studies have proposed that developmentally distinct tissue MPhi can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we took advantage of an inducible fate-mapping system that facilitated the identification of CD45(+)c-kit(-)CX3CR1(+)F4/80(+) (A2) progenitors of the YS as the source of F4/80(hi) but not CD11b(hi) MPhi. Large-scale transcriptional profiling of MPhi precursors from the YS stage to adulthood allowed for building computational models for F4/80(hi) tissue macrophages being direct descendants of A2 progenitors. We further identified a distinct molecular signature of F4/80(hi) and CD11b(hi) MPhi and found that Irf8 was vital for MPhi maturation. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MPhi. PMID- 27412701 TI - Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 receptor agonist, in African-American people with Type 2 diabetes: a meta analysis of sub-population data from seven phase III trials. AB - AIM: To evaluate the efficacy and safety of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide in African-American people with Type 2 diabetes. METHODS: Analyses were performed on patient-level data from individuals self defined as African-American or non-African-American in seven phase III studies. Endpoints included change in HbA1c level, fasting plasma glucose level and body weight from baseline, proportion of patients reaching HbA1c target [< 53 mmol/mol (< 7.0%)], and incidence of hypoglycaemia and nausea. Analyses used data obtained after 26 weeks. Within-population comparisons of liraglutide were performed vs placebo for African-American and non-African-American patient groups. In addition, between-population comparisons with non-African-American patients were performed for each treatment. RESULTS: In African-American patients (n = 225), HbA1c was significantly reduced at 26 weeks with liraglutide 1.2 and 1.8 mg (-11 and -14 mmol/mol, respectively compared with placebo; P < 0.0001). There were also significant reductions in fasting plasma glucose (-2.4 and -3.1 mmol/l, respectively, compared with placebo; P < 0.0001). Statistically significant reductions in body weight were observed with 1.8 mg liraglutide (-2.1 kg compared with placebo; P = 0.0056), but not with 1.2 mg liraglutide (-0.26 kg; P = 0.7307). The P value for interaction between treatment and race was significant for body weight (P = 0.0355). The incidence of non-severe hypoglycaemia with liraglutide was low (11-15% of patients), and < 25% of patients receiving liraglutide experienced nausea. CONCLUSIONS: This meta-analysis suggests that liraglutide is well tolerated and efficacious for treatment of Type 2 diabetes in African-American patients, with an efficacy that was shown not to differ from that observed in non-African-American patients over 26 weeks. PMID- 27412703 TI - Plasma membrane cholesterol level and agonist-induced internalization of delta opioid receptors; colocalization study with intracellular membrane markers of Rab family. AB - Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-delta-OR by beta-cyclodextrin (beta-CDX) resulted in a slight internalization of delta-OR. Massive internalization of delta-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of delta-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-delta-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in beta-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-delta-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-delta-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-delta-OR. Major part of FLAG-delta-OR was co-localized with plasma membrane marker Na,K-ATPase and beta-CDX treatment resulted in shift of PM fragments containing both FLAG-delta-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments. PMID- 27412702 TI - Lentiviral Delivery of miR-133b Improves Functional Recovery After Spinal Cord Injury in Mice. AB - Based on the observation that microRNA (miRNA) 133b enhances regeneration after spinal cord injury in the adult zebrafish, we investigated whether this miRNA would be beneficial in a mammalian system in vitro and in vivo. We found that infection of cultured neurons with miR-133b promotes neurite outgrowth in vitro on an inhibitory substrate consisting of mixed chondroitin sulfate proteoglycans, when compared to infection with green fluorescent protein (GFP) for control. In vivo, viral infection of the injured adult mouse spinal cord at the time of injury at and in the vicinity of the lesion site enhanced expression of miR-133b. Measurements of locomotor recovery by Basso Mouse Scale (BMS) showed improvement of recovery starting at 4 weeks after injury and virus injection. This improvement was associated with downregulation of the expression levels of Ras homolog gene family member A (RhoA), chondroitin sulfate proteoglycans, and microglia/macrophage marker in the spinal cord as assayed 6 weeks after injury. Potential inhibitory molecules carrying consensus sequences for binding of miR 133b were identified in silico and verified in a reporter assay in vitro showing reductions in expression of RhoA, xylosyltransferase 1 (Xylt1), ephrin receptor A7 (Epha7), and purinergic receptor P2X ligand-gated ion channel 4 (P2RX4). These results encourage targeting miR-133 for therapy. PMID- 27412704 TI - A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1. AB - BACKGROUND: With cases of emergence of drug resistance to the current competitive inhibitors of neuraminidase (NA) such as oseltamivir and zanamavir, there is a present need for an alternative approach in the treatment of avian influenza. With this in view, some flavones and chalcones were designed based on quercetin, the most active naturally occurring noncompetitive inhibitor. OBJECTIVE: We attempt to understand the binding of quercetin to H5N1-NA, and synthetic analogs of quercetin namely flavones and its precursors the chalcones using computational tools. METHODS: Molecular docking was done using Libdock. Molecular dynamics (MD) simulations were performed using Amber14. We synthesized the two compounds; their structures were confirmed by infrared spectroscopy, 1H-NMR, and mass spectrometry. These molecules were then tested for H5N1-NA inhibition and kinetics of inhibition. RESULTS: Molecular docking studies yielded two compounds i.e., 4'-methoxyflavone and 2'-hydroxy-4-methoxychalcone, as promising leads which identified them as binders of the 150-cavity of NA. Furthermore, MD simulation studies revealed that quercetin and the two compounds bind and hold the 150 loop in its open conformation, which ultimately perturbs the binding of sialic acid in the catalytic site. Estimation of the free energy of binding by MM PBSA portrays quercetin as more potent than chalcone and flavone. These molecules were then determined as non-competitive inhibitors from the Lineweaver-Burk plots rendered from the enzyme kinetic studies. CONCLUSION: We conclude that non competitive type of inhibition, as shown in this study, can serve as an effective method to block NA and evade the currently seen drug resistance. PMID- 27412705 TI - Occurrence and spread of influenza A(H1N1)pdm09 virus infection in Norwegian pig herds based on active serosurveillance from 2010 to 2014. AB - The incursion of influenza A(H1N1)pdm09 virus was detected by Norway's active serosurveillance of its pig population in 2009. Since then, surveillance data from 2010 to 2014 revealed that 54% of 5643 herd tests involving 1567 pig herds and 28% of 23 036 blood samples screened positive for antibodies against influenza A virus. Positive herds were confirmed to have influenza A(H1N1)pdm09 virus infection by haemagglutination inhibition test. In 50% of positive herd tests, ?60% of the sampled pigs in each herd had antibodies against influenza A(H1N1)pdm09 virus. This within-herd animal seroprevalence did not vary for type of production, herd size or year of test. The overall running mean of national herd seroprevalence, and annual herd incidence risks fluctuated narrowly around the means of 45% and 32%, respectively, with the highest levels recorded in the three densest pig-producing counties. The probability of a herd being seropositive varied in the five production classes, which were sow pools, multiplier herds, conventional sow herds, nucleus herds, and fattening herds in descending order of likelihood. Large herds were more likely to be seropositive. Seropositive herds were highly likely to be seropositive the following year. The study shows that influenza A(H1N1)pdm09 virus is established in the Norwegian pig population with recurrent and new herd infections every year with the national herd seroprevalence in 2014 hovering at around 43% (95% confidence interval 40 46%). PMID- 27412706 TI - Probiotics modulate gut microbiota and health status in Japanese cedar pollinosis patients during the pollen season. AB - BACKGROUND: Japanese cedar pollinosis (JCP) is a challenging public health problem in Japan. Altered gut microbiota is associated with several diseases, including allergic diseases. However, only a few studies have focused on JCP and the underlying mechanisms for probiotic effects remain unclear. In addition, this study is the first observation of the correlation between the gut microbiota and blood lipid in JCP. METHODS: Faecal samples from JCP subjects were collected before and after treatment with (n = 14) and without (n = 11) LGG-TMC0356 fermented milk for 10 weeks. Gut microbiota composition was characterized from faecal DNA using sequencing of 16S rRNA genes. RESULTS: 16S rRNA-based operational taxonomic unit clustering of the microbiota revealed that LGG-TMC0356 fermented milk significantly altered gut microbiota after 10 weeks of milk consumption, and eight dominant genera of microbes were detected. During the JCP season, the Bacteroidetes/Firmicutes ratio, when compared to baseline, was significantly decreased in subjects at end of the study. Bacteroidetes showed positive correlation with LDL- and HDL-cholesterol levels, whereas Firmicutes showed negative correlation with total cholesterol, LDL- and HDL- cholesterol. CONCLUSIONS: The altered gut microbiota through supplementation of fermented milk containing the study probiotics may be a prospective target for protection against JCP, with beneficial effects on blood lipid levels. PMID- 27412707 TI - Fermented goat milk consumption during anaemia recovery: ergogenic effect and improvement of skeletal muscle homeostasis. AB - PURPOSE: Anaemia is associated with fatigue and diminished muscular oxygenation, which may affect skeletal muscle (SM). No studies are available about the SM modifications during anaemia recovery; therefore, the aim of this study is to study SM homeostasis during anaemia recovery with fermented milks. METHODS: Forty male Wistar rats were placed on a pre-experimental period of 40 days, divided in two groups (control group receiving normal-Fe diet and Fe-deficient group receiving low-Fe diet). Lately, rats were fed with fermented goat or cow milk based diets, with normal-Fe content during 30 days. After feeding the fermented milks, leptin, adiponectin, non-esterified fatty acids (NEFA) and protein expression (UCP1, PepT1 and irisin) within the SM were assessed. RESULTS: Adiponectin decreased in both groups of animals fed fermented goat milk, while leptin and NEFA increased. UCP1 protein expression increased in control and anaemic animals fed fermented goat milk. UCP1 also increased in both group of anaemic animals fed either fermented cow or goat milk in comparison with their controls. Irisin increased in both group of animals fed fermented goat milk. Finally, PepT1 also showed an increased expression in control and anaemic rats fed fermented goat milk and the anaemia also induced an over-expression of this transporter in animals fed either fermented cow or goat milk. CONCLUSION: Fermented goat milk consumption during anaemia recovery diminishes adiposity depots and enhances lipolysis, increasing UCP1, PepT1 and irisin protein expression, featuring an ergogenic effect in the SM which is an important endocrine regulator of body metabolism. PMID- 27412708 TI - Bad math in Linnaeus' Philosophia Botanica. AB - In Philosophia Botanica (1751), Carolus Linnaeus (1707-1778) presented a calculation of the number of plant genera that may be distinguished based on his taxonomic concepts. In order to derive that number, he relied upon the organs of fructification, which represent the flower and the fruit, by selecting over 30 elements from them, and then assuming that each could vary by four dimensions. However, while Linnaeus was good in counting stamens and pistils, he and many of his followers who edited or translated Philosophia Botanica were less careful, basing their calculations of the number of possible genera on flawed assumptions, or even introducing basic arithmetic errors. Furthermore, although mathematics was quite advanced in the eighteenth century, the gap between combinatorial and botanical thinking was too deep, preventing Linnaeus to seek a reasonable solution to the problem he raised. The authors demonstrate this by a historical analysis of 15 editions of Philosophia Botanica, plus many references to it, and conclude that the desired number almost always appeared in error during the past 265 years. The German botanist J. G. Gleditsch (1714-1786) was the most successful with respect to Linnaeus' original intention. Elementary mathematics demonstrates that if Linnaeus' assumptions were taken seriously, then the possible number of genera would be astronomical. The practice he followed in Genera Plantarum (1754) shows, however, that the fructification dimensions served as a universal set for Linnaeus from which he chose only the relevant ones for describing a particular genus empirically. Based on the corrections and modifications implemented in reworked editions, we suggest an evolutionary network for the historical and modern versions or translations of Philosophia Botanica. PMID- 27412709 TI - [Weaning ward-different from the ICU?] AB - Weaning from mechanical ventilation is generally not the most urgent topic on many ICUs, because acutely endangered patients are usually the staff's main focus. Nevertheless, even these patients whose underlying problem has been mostly solved-whether it was neurologic, internal or surgical-are in need of a structured weaning strategy. The aim of this weaning "road map" is ventilator independence, decannulation and regaining of muscular strength. Achieving of these aims needs a well-educated team of physicians, nurses, respiratory/physical therapists, logopedists and pychologists. Assessment of patient health status, including respiratory muscle function must be part of the overtaking procedure to be able to focus on the main problem that may be causative for the inability to wean so far. Every weaning unit must be able to organize the future treatment of patients (different ward inside the hospital, rehabilitation) or the transfer into a (ventilated) home care situation. PMID- 27412710 TI - A Statistical Guide to the Design of Deep Mutational Scanning Experiments. AB - The characterization of the distribution of mutational effects is a key goal in evolutionary biology. Recently developed deep-sequencing approaches allow for accurate and simultaneous estimation of the fitness effects of hundreds of engineered mutations by monitoring their relative abundance across time points in a single bulk competition. Naturally, the achievable resolution of the estimated fitness effects depends on the specific experimental setup, the organism and type of mutations studied, and the sequencing technology utilized, among other factors. By means of analytical approximations and simulations, we provide guidelines for optimizing time-sampled deep-sequencing bulk competition experiments, focusing on the number of mutants, the sequencing depth, and the number of sampled time points. Our analytical results show that sampling more time points together with extending the duration of the experiment improves the achievable precision disproportionately compared with increasing the sequencing depth or reducing the number of competing mutants. Even if the duration of the experiment is fixed, sampling more time points and clustering these at the beginning and the end of the experiment increase experimental power and allow for efficient and precise assessment of the entire range of selection coefficients. Finally, we provide a formula for calculating the 95%-confidence interval for the measurement error estimate, which we implement as an interactive web tool. This allows for quantification of the maximum expected a priori precision of the experimental setup, as well as for a statistical threshold for determining deviations from neutrality for specific selection coefficient estimates. PMID- 27412711 TI - Bayesian Inference of the Evolution of a Phenotype Distribution on a Phylogenetic Tree. AB - The distribution of a phenotype on a phylogenetic tree is often a quantity of interest. Many phenotypes have imperfect heritability, so that a measurement of the phenotype for an individual can be thought of as a single realization from the phenotype distribution of that individual. If all individuals in a phylogeny had the same phenotype distribution, measured phenotypes would be randomly distributed on the tree leaves. This is, however, often not the case, implying that the phenotype distribution evolves over time. Here we propose a new model based on this principle of evolving phenotype distribution on the branches of a phylogeny, which is different from ancestral state reconstruction where the phenotype itself is assumed to evolve. We develop an efficient Bayesian inference method to estimate the parameters of our model and to test the evidence for changes in the phenotype distribution. We use multiple simulated data sets to show that our algorithm has good sensitivity and specificity properties. Since our method identifies branches on the tree on which the phenotype distribution has changed, it is able to break down a tree into components for which this distribution is unique and constant. We present two applications of our method, one investigating the association between HIV genetic variation and human leukocyte antigen and the other studying host range distribution in a lineage of Salmonella enterica, and we discuss many other potential applications. PMID- 27412714 TI - The timing of mandibular tooth formation in two African groups. AB - BACKGROUND: Ethnic differences in the timing of human tooth development are unclear. AIM: To describe similarities and differences in the timing of tooth formation in two groups of Sudanese children and young adults. SUBJECTS AND METHODS: The sample consisted of healthy individuals from Khartoum, Sudan, aged 2 23 years. The Northern group was of Arab origin (848 males, 802 females) and the Western group was of African origin (846 males, 402 females). Each mandibular left permanent tooth from first incisor to third molar was assessed from dental radiographs into one of 15 development stages. Mean ages at entry for 306 tooth stages were calculated using probit regression in males/females in each group and compared using a t-test. RESULTS: Mean ages were not significantly different in most tooth stage comparisons between ethnic groups for both males (61/75) and females (56/76), despite a tendency of earlier mean ages in the Western group. Mean ages for most tooth stage comparisons between males and females (137/155) were not significantly different within ethnic groups suggesting low sexual dimorphism. CONCLUSION: The mean ages of most mandibular tooth formation stages were generally not significantly different between ethnic groups or between males and females in this study. PMID- 27412713 TI - Genetic Architecture of Domestication-Related Traits in Maize. AB - Strong directional selection occurred during the domestication of maize from its wild ancestor teosinte, reducing its genetic diversity, particularly at genes controlling domestication-related traits. Nevertheless, variability for some domestication-related traits is maintained in maize. The genetic basis of this could be sequence variation at the same key genes controlling maize-teosinte differentiation (due to lack of fixation or arising as new mutations after domestication), distinct loci with large effects, or polygenic background variation. Previous studies permit annotation of maize genome regions associated with the major differences between maize and teosinte or that exhibit population genetic signals of selection during either domestication or postdomestication improvement. Genome-wide association studies and genetic variance partitioning analyses were performed in two diverse maize inbred line panels to compare the phenotypic effects and variances of sequence polymorphisms in regions involved in domestication and improvement to the rest of the genome. Additive polygenic models explained most of the genotypic variation for domestication-related traits; no large-effect loci were detected for any trait. Most trait variance was associated with background genomic regions lacking previous evidence for involvement in domestication. Improvement sweep regions were associated with more trait variation than expected based on the proportion of the genome they represent. Selection during domestication eliminated large-effect genetic variants that would revert maize toward a teosinte type. Small-effect polygenic variants (enriched in the improvement sweep regions of the genome) are responsible for most of the standing variation for domestication-related traits in maize. PMID- 27412712 TI - Effector-Triggered Immune Response in Arabidopsis thaliana Is a Quantitative Trait. AB - We identified loci responsible for natural variation in Arabidopsis thaliana (Arabidopsis) responses to a bacterial pathogen virulence factor, HopAM1. HopAM1 is a type III effector protein secreted by the virulent Pseudomonas syringae strain Pto DC3000. Delivery of HopAM1 from disarmed Pseudomonas strains leads to local cell death, meristem chlorosis, or both, with varying intensities in different Arabidopsis accessions. These phenotypes are not associated with differences in bacterial growth restriction. We treated the two phenotypes as quantitative traits to identify host loci controlling responses to HopAM1. Genome wide association (GWA) of 64 Arabidopsis accessions identified independent variants highly correlated with response to each phenotype. Quantitative trait locus (QTL) mapping in a recombinant inbred population between Bur-0 and Col-0 accessions revealed genetic linkage to regions distinct from the top GWA hits. Two major QTL associated with HopAM1-induced cell death were also associated with HopAM1-induced chlorosis. HopAM1-induced changes in Arabidopsis gene expression showed that rapid HopAM1-dependent cell death in Bur-0 is correlated with effector-triggered immune responses. Studies of the effect of mutations in known plant immune system genes showed, surprisingly, that both cell death and chlorosis phenotypes are enhanced by loss of EDS1, a regulatory hub in the plant immune-signaling network. Our results reveal complex genetic architecture for response to this particular type III virulence effector, in contrast to the typical monogenic control of cell death and disease resistance triggered by most type III effectors. PMID- 27412715 TI - Recurrence and Survival After Gross Total Removal of Resectable Undifferentiated or Poorly Differentiated Thyroid Carcinoma. AB - BACKGROUND: This study aimed to evaluate the recurrence and survival after initial curative-intent surgery of resectable anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who had been treated between 1985 and 2013. Among them, 119 patients who had undergone surgery with curative intent were included in this study. The outcome measures included the clinical response to treatment and the recurrence rates of three separate thyroid cancer groups: ATC, differentiated thyroid cancer (DTC) with anaplastic foci, and PDTC. RESULTS: Initial remission was achieved in 100 (84.0%) patients, with higher percentages in patients with DTC with anaplastic foci (97.8%) and PDTC (96.7%) compared with ATC (60.5%). The overall recurrence rate after initial remission was 30.8% in ATC, 25.9% in PDTC, and 6.7% in DTC with anaplastic foci. Pathologic diagnosis, preexisting goiter or tumors, along with tracheal and lymphatic/vascular invasion were correlated with recurrence (p < 0.001; p = 0.001, 0.006, 0.003, and 0.016, respectively). All patients without initial remission died due to local failure, and most patients with recurrence, apart from two PDTC patients, had distant metastasis. Overall mortality after initial curative-intent surgery was 58.1% in ATC, 8.7% in DTC with anaplastic foci, and 20% in PDTC. CONCLUSIONS: The initial remission of resectable tumors was higher and the recurrence rate was lower in DTC with anaplastic foci and PDTC compared with ATC. Careful monitoring of the development of distant metastasis is necessary, especially in patients with aggressive pathology with tracheal and lymphovascular invasion. PMID- 27412716 TI - Great genetic diversity of rotaviruses detected in piglets with diarrhea in Thailand. AB - A total of 491 fecal specimens collected from diarrheic piglets in Thailand from January 2011 to March 2014 were screened for group A rotavirus by RT-PCR assay. The G and P genotypes of the detected rotaviruses were determined by multiplex PCR or nucleotide sequencing. Group A rotaviruses were detected in 113 out of 491 (23.0 %) fecal specimens. A wide variety of G-P genotype combinations were identified, and G4P[13] was the most prevalent genotype combination (29.2 %), followed by G4P[23] (14.1 %), G5P[23] (11.5 %), G4P[6] (9.7 %), G3P[23] (7.0 %), G5P[13] (6.1 %), G3P[13] (4.4 %), G3P[6] (2.7 %), and G5P[6] (2.7 %). In addition, the other G-P combinations were also detected at a low percentage, including G3P[19], G4P[7], G9P[19], G9P[23], G9P[7], G4P[19], and G11P[13] strains. This study indicated that group A rotaviruses are a common causes of diarrhea in piglets and a great diversity of G and P genotype combinations are circulating in piglets in Thailand. PMID- 27412717 TI - Expression of soluble human Neonatal Fc-receptor (FcRn) in Escherichia coli through modification of growth environment. AB - Neonatal Fc-receptor (FcRn) with its affinity to immunoglobulin G (IgG) has been the subject of many pharmacokinetic studies in the past century. This protein is well known for its unique feature in maintaining the circulating IgG from degradation in blood plasma. FcRn is formed by non-covalent association between the alpha-chain with the beta-2-microglobulin (beta2m). Many studies have been conducted to produce FcRn in the laboratory, mainly using mammalian tissue culture as host for recombinant protein expression. In this study, we demonstrate a novel strategy to express the alpha-chain of FcRn using Escherichia coli as the expression host. The expression vector that carries the cDNA of the alpha-chain was transformed into expression host, Rosetta-gami 2 strain for inducible expression. The bacterial culture was grown in a modified growth medium which constitutes of terrific broth, sodium chloride (NaCl), glucose and betaine. A brief heat shock at 45 degrees C was carried out after induction, before the temperature for expression was reduced to 22 degrees C and grown for 16 h. The soluble form of the alpha-chain of FcRn expressed was tested in the ELISA and dot blot immunoassay to confirm its native functionality. The results implied that the alpha-chain of FcRn expressed using this method is functional and retains its pH-dependent affinity to IgG. Our study significantly suggests that the activity of human FcRn remain active and functional in the absence of beta2m. PMID- 27412718 TI - Novel pharmacological inhibitors demonstrate the role of the tyrosine kinase Pyk2 in adhesion and aggregation of human platelets. AB - Pyk2 is a Ca2+-regulated kinase predominantly expressed in neuronal and in haematopoietic cells. Previous studies on Pyk2-null mice have demonstrated that Pyk2 plays a crucial role in platelet activation and thrombus formation, thus representing a possible target for antithrombotic therapy. Very limited information is available about the role of Pyk2 in human platelets, mainly because of the lack of specific pharmacological inhibitors. In this work, we have tested two novel Pyk2 inhibitors, PF-4594755 and PF-4520440, to validate their specificity and to investigate their ability to modulate platelet activation. Both molecules were able to efficiently block Pyk2 activity in human and mouse platelets stimulated with thrombin or with the Ca2+-ionophore. In wild-type murine platelets, PF-4594755 and PF-4520440 reduced thrombin-induced aggregation to the level observed in Pyk2 knockout platelets, but did not affect aggregation induced by GPVI stimulation. Importantly, neither compounds affected the residual thrombin-induced aggregation of Pyk2-null platelets, thus excluding possible off target effects. In human platelets, PF-4594755 and PF-4520440 significantly reduced aggregation stimulated by thrombin, but not by the GPVI agonist convulxin. Both inhibitors reduced platelet adhesion on fibrinogen and prevented Akt phosphorylation in adherent cells, indicating that Pyk2 regulates PI3K and cell spreading downstream of integrins in human platelets. Finally, the Pyk2 inhibitors significantly inhibited thrombus formation upon blood perfusion on immobilized collagen under arterial flow rate. These results demonstrate that PF 4594755 and PF-4520440 are specific inhibitors of Pyk2 in intact platelets and allowed to reliably document that this kinase plays a relevant role in human platelet activation. PMID- 27412719 TI - Lipingzhangella halophila gen. nov., sp. nov., a new member of the family Nocardiopsaceae. AB - An alkaliphilic and halophilic actinomycete strain, designated EGI 80537T, was isolated from a saline-alkali soil sample of Xinjiang, north-west China and subjected to a taxonomic characterization using a polyphasic approach. Strain EGI 80537T formed reticulate long aerial hyphae. Whole-cell hydrolysates of the isolate contained meso-diaminopimelic acid as the cell-wall diamino acid and mannose as the diagnostic sugar. The major fatty acids identified were iso-C16 : 0, anteiso-C17 : 0 and 10-methyl-C18 : 0 (TBSA). The predominant menaquinones detected were MK-10(H8) and MK-10(H6). The G+C content of the genomic DNA of strain EGI 80537T was 67.6 mol%. Strain EGI 80537T showed the highest 16S rRNA gene sequence similarity to Allosalinactinospora lopnorensis CA15-2T (96.7 %). Phylogenetic analysis showed that strain EGI 80537T clustered with the members of the family Nocardiopsaceae. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain EGI 80537T represents a novel species of a new genus in the family Nocardiopsaceae, for which the name Lipingzhangella halophila gen. nov., sp. nov. is proposed. The type strain of the type species is EGI 80537T(=CGMCC 4.7224T= DSM 102030T). PMID- 27412720 TI - Proteomics of hydrophobic samples: Fast, robust and low-cost workflows for clinical approaches. AB - In a comparative study, we investigated the influence of nine sample preparation workflows and seven different lysis buffers for qualitative and quantitative analysis of the human adipose tissue proteome. Adipose tissue is not just a fat depot but also an endocrine organ, which cross-talks with other tissue types and organs throughout the body, like liver, muscle, pancreas, and brain. Its secreted molecules have an influence on the nervous, immune, and vascular system, thus adipose tissue plays an important role in the regulation of whole-body homeostasis. Proteomic analysis of adipose tissue is challenging due to the extremely high lipid content and a variety of different cell types included. We investigated the influence of different detergents to the lysis buffer and compared commonly used methods like protein precipitation and filter-aided sample preparation (FASP) with workflows involving acid labile or precipitable surfactants. The results indicate that a sodium deoxycholate (SDC) based workflow had the highest efficiency and reproducibility for quantitative proteomic analysis. In total 2564 proteins from the adipose tissue of a single person were identified. PMID- 27412721 TI - Breeding signature of combining ability improvement revealed by a genomic variation map from recurrent selection population in Brassica napus. AB - Combining ability is crucial for parent selection in crop hybrid breeding. The present investigation and results had revealed the underlying genetic factors which might contribute in adequate combining ability, further assisting in enhancing heterosis and stability. Here, we conducted a large-scale analysis of genomic variation in order to define genomic regions affecting the combining ability in recurrent selection population of rapeseed. A population of 175 individuals was genotyped with the Brassica60K SNP chip. 525 hybrids were assembled with three different testers and used to evaluate the general combining ability (GCA) in three environments. By detecting the changes of the genomic variation, we identified 376 potential genome regions, spanning 3.03% of rapeseed genome which provided QTL-level resolution on potentially selected variants. More than 96% of these regions were located in the C subgenome, indicating that C subgenome had sustained stronger selection pressure in the breeding program than the A subgenome. In addition, a high level of linkage disequilibrium in rapeseed genome was detected, suggesting that marker-assisted selection for the population improvement might be easily implemented. This study outlines the evidence for high GCA on a genomic level and provided underlying molecular mechanism for recurrent selection improvement in B. napus. PMID- 27412722 TI - Chloroquine enhanced the anticancer capacity of VNP20009 by inhibiting autophagy. AB - Bacteria-based living anticancer agents have emerged as promising therapeutics. However, the functional role of autophagy in bacterial cancer therapy has been little investigated. In this study, Salmonella VNP20009 induced autophagy in B16F10 cells, which is an unfavorable factor in bacterial cancer therapy. Inhibiting the induction of autophagy by chloroquine or siRNA in bacterial cancer therapy dose- and time-dependently promoted cell death. The combined therapy of VNP20009 and chloroquine not only enhanced the bacterial tumor targeting ability but also facilitated the infiltration of immune cells into the tumor. Our results showed that the combined therapy of VNP20009 and chloroquine could significantly inhibit tumor growth and prolong mouse survival time. This study provides a novel strategy for improving the anti-cancer efficacy of bacterial cancer therapy. PMID- 27412724 TI - Glycerol-fed microbial fuel cell with a co-culture of Shewanella oneidensis MR-1 and Klebsiella pneumonae J2B. AB - Glycerol is an attractive feedstock for bioenergy and bioconversion processes but its use in microbial fuel cells (MFCs) for electrical energy recovery has not been investigated extensively. This study compared the glycerol uptake and electricity generation of a co-culture of Shewanella oneidensis MR-1 and Klebsiella pneumonia J2B in a MFC with that of a single species inoculated counterpart. Glycerol was metabolized successfully in the co-culture MFC (MFC J&M) with simultaneous electricity production but it was not utilized in the MR-1 only MFC (MFC-M). A current density of 10 mA/m(2) was obtained while acidic byproducts (lactate and acetate) were consumed in the co-culture MFC, whereas they are accumulated in the J2B-only MFC (MFC-J). MR-1 was distributed mainly on the electrode in MFC-J&M, whereas most of the J2B was observed in the suspension in the MFC-J reactor, indicating that the co-culture of both strains provides an ecological driving force for glycerol utilization using the electrode as an electron acceptor. This suggests that a co-culture MFC can be applied to electrical energy recovery from glycerol, which was previously known as a refractory substrate in a bioelectrochemical system. PMID- 27412725 TI - A rational synthesis of hierarchically porous, N-doped carbon from Mg-based MOFs: understanding the link between nitrogen content and oxygen reduction electrocatalysis. AB - Controlled mixtures of novel Mg-based metal-organic frameworks (MOFs) were prepared, with H(+) or K(+) as counterions. A linear relation was found between synthesis pH and K/H ratio in the resultant mixture, establishing the tunability of the synthesis. Upon pyrolysis, these precursor mixtures yield nitrogen-doped, hierarchically porous carbons, which have good activity towards the oxygen reduction reaction (ORR) at pH 13. The nitrogen content varies significantly along the homologous carbon series (>400%, 1.3 at% to 5.7 at%), to a much greater extent than microstructural parameters such as surface area and graphitization. This allows us to isolate the positive correlation between nitrogen content and electrocatalytic oxygen reduction ORR activity in this class of metal-free, N doped, porous carbons. PMID- 27412723 TI - An efficient method for gene silencing in human primary plasmacytoid dendritic cells: silencing of the TLR7/IRF-7 pathway as a proof of concept. AB - Plasmacytoid dendritic cells (pDC) are specialized immune cells that produce massive levels of type I interferon in response to pathogens. Unfortunately, pDC are fragile and extremely rare, rendering their functional study a tough challenge. However, because of their central role in numerous pathologies, there is a considerable need for an efficient and reproducible protocol for gene silencing in these cells. In this report, we tested six different methods for siRNA delivery into primary human pDC including viral-based, lipid-based, electroporation, and poly-ethylenimine (PEI) technologies. We show that lipid based reagent DOTAP was extremely efficient for siRNA delivery into pDC, and did not induce cell death or pDC activation. We successfully silenced Toll-Like Receptor 7 (TLR7), CXCR4 and IFN regulatory factor 7 (IRF-7) gene expression in pDC as assessed by RT-qPCR or cytometry. Finally, we showed that TLR7 or IRF-7 silencing in pDC specifically suppressed IFN-alpha production upon stimulation, providing a functional validation of our transfection protocol. PMID- 27412726 TI - Towards an evidence-based model of fear of cancer recurrence for breast cancer survivors. AB - PURPOSE: In order to understand the multidimensional mechanism of fear of cancer recurrence (FCR) and to identify potential targets for interventions, it is important to empirically test the theoretical model of FCR. This study aims at assessing the validity of Lee-Jones et al.'s FCR model. METHODS: A total of 1205 breast cancer survivors were invited to participate in this study. Participants received a questionnaire booklet including questionnaires on demographics and psychosocial variables including FCR. Data analysis consisted of the estimation of direct and indirect effects in mediator models. RESULTS: A total of 460 women (38 %) participated in the study. Median age was 55.8 years (range 32-87). Indirect effects of external and internal cues via FCR were found for all mediation models with limited planning for the future (R 2 = .28) and body checking (R 2 = .11-.15) as behavioral response variables, with the largest effects for limited planning for the future. A direct relation was found between feeling sick and seeking professional advice, not mediated by FCR. CONCLUSIONS: In the first tested models of FCR, all internal and external cues were associated with higher FCR. In the models with limited planning for the future and body checking as behavioral response, an indirect effect of cues via FCR was found supporting the theoretical model of Lee-Jones et al. IMPLICATIONS FOR CANCER SURVIVORS: An evidence-based model of FCR may facilitate the development of appropriate interventions to manage FCR in breast cancer survivors. PMID- 27412727 TI - Mitochondrial Dysfunction in Psychiatric Illness. PMID- 27412729 TI - Cost-Effectiveness Results for Early Psychosis Intervention Programs Are Influenced by the Perspective Taken. PMID- 27412730 TI - Measuring sequences of keystrokes with jsPsych: Reliability of response times and interkeystroke intervals. AB - Although the precision and reliability of response time (RT) measurements performed via Web-based interfaces have been evaluated, sequences of keystrokes have never been investigated in detail. Keystrokes often occur in much more rapid succession than RTs, and operating systems may interpret successive or concomitant keyboard events according to both automatic and user-based settings. Sequence keystroke timing could thus be more sensitive than single RTs to noise in online measurements. Here, we quantified the precision and reliability of timing measures performed during sequences of keystrokes. We used the JavaScript jsPsych library to create an experiment involving finger-movement sequences, and ran it online with 633 participants. We manipulated the structure of three keystroke motor sequences, targeting a replication of previous findings regarding both RTs and interkeystroke intervals (IKIs). Our online data accurately reproduced the original results and allowed for a novel assessment of demographic variables such as age and gender. In parallel, we also measured the objective timing accuracy of the jsPsych interface by using specialized hardware and software, showing a constant 60-ms delay for RTs and a 0-ms delay for IKIs across the sequences. The distribution of IKIs revealed quantizing for a majority of participants, most likely due to the sampling frequency of their USB keyboards. Overall, these findings indicate that JsPsych provides good reliability and accuracy in sequence keystroke timings for mental chronometry purposes, through online recordings. PMID- 27412731 TI - A miniaturized electrochemical device integrating a biconical microchannel and carbon fiber disk ultramicroelectrode. AB - A simple, cheap and practicable miniaturized electrochemical device based on a biconical microchannel was developed, for which only 1 MUL sample solution was needed to implement a typical electrochemical experiment. The practicability of the designed device was validated by detecting uric acid as a model molecule in human serum. PMID- 27412728 TI - Mitochondrial Oxidative Phosphorylation System (OXPHOS) Deficits in Schizophrenia: Possible Interactions with Cellular Processes. AB - Mitochondria are key players in the generation and regulation of cellular bioenergetics, producing the majority of adenosine triphosphate molecules by the oxidative phosphorylation system (OXPHOS). Linked to numerous signaling pathways and cellular functions, mitochondria, and OXPHOS in particular, are involved in neuronal development, connectivity, plasticity, and differentiation. Impairments in a variety of mitochondrial functions have been described in different general and psychiatric disorders, including schizophrenia (SCZ), a severe, chronic, debilitating illness that heavily affects the lives of patients and their families. This article reviews findings emphasizing the role of OXPHOS in the pathophysiology of SCZ. Evidence accumulated during the past few decades from imaging, transcriptomic, proteomic, and metabolomic studies points at OXPHOS deficit involvement in SCZ. Abnormalities have been reported in high-energy phosphates generated by the OXPHOS, in the activity of its complexes and gene expression, primarily of complex I (CoI). In addition, cellular signaling such as cAMP/protein kinase A (PKA) and Ca(+2), neuronal development, connectivity, and plasticity have been linked to OXPHOS function and are reported to be impaired in SCZ. Finally, CoI has been shown as a site of interaction for both dopamine (DA) and antipsychotic drugs, further substantiating its role in the pathology of SCZ. Understanding the role of mitochondria and the OXPHOS in particular may encourage new insights into the pathophysiology and etiology of this debilitating disorder. PMID- 27412733 TI - High-Performance Blue OLEDs Based on Phenanthroimidazole Emitters via Substitutions at the C6- and C9-Positions for Improving Exciton Utilization. AB - Donor-acceptor (D-A) molecular architecture has been shown to be an effective strategy for obtaining high-performance electroluminescent materials. In this work, two D-A molecules, Ph-BPA-BPI and Py-BPA-BPI, have been synthesized by attaching highly fluorescent phenanthrene or pyrene groups to the C6- and C9 positions of a locally excited-state emitting phenylamine-phenanthroimidazole moiety. Equipped with good physical and hybridized local and charge-transfer properties, both molecules show high performances as blue emitters in nondoped organic light-emitting devices (OLEDs). An OLED using Ph-BPA-BPI as the emitting layer exhibits deep-blue emission with CIE coordinates of (0.15, 0.08), and a maximum external quantum efficiency (EQE), current efficiency (CE), and power efficiency (PE) of 4.56 %, 3.60 cd A(-1) , and 3.66 lm W(-1) , respectively. On the other hand, a Py-BPA-BPI-based, sky-blue OLED delivers the best results among nondoped OLEDs with CIEy values of < 0.3 reported so far, for which a very low turn-on voltage of 2.15 V, CIE coordinates of (0.17, 0.29), and maximum CE, PE, and EQE values of 10.9 cd A(-1) , 10.5 lm W(-1) , and 5.64 %, were achieved, respectively. More importantly, both devices show little or even no efficiency roll-off and high singlet exciton-utilizing efficiencies of 36.2 % for Ph-BPA-BPI and 39.2 % for Py-BPA-BPI. PMID- 27412732 TI - Tracking Cancer Genetic Evolution using OncoTrack. AB - It is difficult for existing methods to quantify, and track the constant evolution of cancers due to high heterogeneity of mutations. However, structural variations associated with nucleotide number changes show repeatable patterns in localized regions of the genome. Here we introduce SPKMG, which generalizes nucleotide number based properties of genes, in statistical terms, at the genome wide scale. It is measured from the normalized amount of aligned NGS reads in exonic regions of a gene. SPKMG values are calculated within OncoTrack. SPKMG values being continuous numeric variables provide a statistical metric to track DNA level changes. We show that SPKMG measures of cancer DNA show a normative pattern at the genome-wide scale. The analysis leads to the discovery of core cancer genes and also provides novel dynamic insights into the stage of cancer, including cancer development, progression, and metastasis. This technique will allow exome data to also be used for quantitative LOH/CNV analysis for tracking tumour progression and evolution with a higher efficiency. PMID- 27412735 TI - [Inproving the knowledge of acute infectious diarrhea in children]. PMID- 27412734 TI - Reverse transcription-polymerase chain reaction molecular testing of cytology specimens: Pre-analytic and analytic factors. AB - The introduction of molecular testing into cytopathology laboratory practice has expanded the types of samples considered feasible for identifying genetic alterations that play an essential role in cancer diagnosis and treatment. Reverse transcription-polymerase chain reaction (RT-PCR), a sensitive and specific technical approach for amplifying a defined segment of RNA after it has been reverse-transcribed into its DNA complement, is commonly used in clinical practice for the identification of recurrent or tumor-specific fusion gene events. Real-time RT-PCR (quantitative RT-PCR), a technical variation, also permits the quantitation of products generated during each cycle of the polymerase chain reaction process. This review addresses qualitative and quantitative pre-analytic and analytic considerations of RT-PCR as they relate to various cytologic specimens. An understanding of these aspects of genetic testing is central to attaining optimal results in the face of the challenges that cytology specimens may present. Cancer Cytopathol 2017;125:11-19. (c) 2016 American Cancer Society. PMID- 27412736 TI - [Practice guideline for acute infectious diarrhea in Chinese children]. PMID- 27412737 TI - [Clinical epidemiology and antimicrobial resistance of nontyphoidal Salmonella enteric infections in children: 2012-2014]. AB - OBJECTIVE: To understand the clinical epidemiology and manifestation of nontyphoidal Salmonella (NTS)enteric infections and serotypes and antibiotic resistance patterns of NTS in children. METHOD: All cases with probable acute bacterial inflammatory diarrhea were included into this study from the Children's Hospital of Fudan University during January 2012 through December 2014. Salmonella species and other major enteric bacteria were routinely isolated from the fresh stool sample of the enrolled patients at their first visit to the enteric clinic. Salmonella isolates were serotyped and tested for antimicrobial susceptibility testing using Kirby-Bauer method at the reference laboratory of Shanghai Municipal Center for Disease Control and Prevention. All enrolled cases had clinical records. The enumeration data were described by constituent ratio. RESULT: Of the enrolled 3 143 patients, 742 (23.6%) were confirmed to have Salmonella infections, and NTS was identified in 738 (23.5%) cases and Salmonella Paratyphi B was identified in 4 (0.1%) cases, respectively. The isolation rate of NTS exceeded diarrheagenic Escherichia coli (6.7%, 182/2 727), Campylobacter (4.1%, 129/3 143) and Shigella (2.4%, 77/3 143). Nine serogroups and 41 serovars were identified in 742 salmonella isolates. Salmonella Enteritidis and Salmonella Typhimurium were the most common serovars, representing 42.6% (316/742) and 28.2% (209/742) of isolates, respectively.NTS infections were prevalent year-round with a seasonal peak from May to October. The common symptoms included fever (57.5%, 424/738) and blood-in-stool (31.0%, 229/738). Antimicrobial susceptibility showed only 8 (1.1%) of 742 isolates sensitive to 16 tested antibiotics.Resistance to the current first-line antibiotics such as the third-generation and(or) fourth generation cephalosporins (cefotaxime and cefepime), ciprofloxacin was detected in 10.0%(74/738), 8.1%(60/738) and 1.1%(8/738), respectively. CONCLUSION: NTS is the leading causative agent responsible for bacterial inflammatory diarrhea in Shanghainese children. The prevalence of NTS enteric infections show an increasing trend year by year. It is essential to continuously monitor the antimicrobial resistance of NTS and trace the source of infection to prevent and treat NTS infections in Shanghai. PMID- 27412738 TI - [Prevalence of Helicobacter pylori infection among children aged 7 to 18 years old: a school-based cross-sectional study in Minhang district of Shanghai in 2014]. AB - OBJECTIVE: To study the infection rate and current infection rate of Helicobacter pylori (Hp) among children aged 7 to 18 years old in Minhang district of Shanghai. METHOD: A school-based cross-sectional study in three elementary and middle schools (with students aged 7 to 18 years old) in Minhang district of Shanghai was conducted. A total of 1 988 students were investigated by questionnaire and non-invasive tests. The positive rate of serum Hp-IgG or (13)C urea breath test was the basis for calculation for Hp infection rate. The positive rate of (13)C urea breath test was the basis for current infection rate. The relationship between infection rate and age was studied through Spearman rank correlation analysis. The consistency of the two diagnostic methods was determined using kappa value analysis. RESULT: A total of 1 988 subjects were included in the analysis: 944 males and 944 females. The Hp infection rate was 36.3%(721/1 988). Current infection rate was 32.1%(625/1 949). Hp infection rates of primary (7-12 years old), junior (13-15 years old), high school group (16-18 years old) were 27.4% (223/813), 33.6% (93/277), 45.1% (405/898) respectively. Hp infection was associated with age, with a correlation coefficient of 0.167 (P<0.001). The kappa value of the serum Hp-IgG and (13)C Urea breath test was 0.67. CONCLUSION: Hp infection rate among children aged 7 to 18 years old in Minhang district of Shanghai is 36.3%, with the infection rate increasing with age. Serum Hp-IgG and the (13)C urea breath test are two detection methods each of which has advantages and disadvantages. PMID- 27412739 TI - [Clinical analysis of enteral nutrition in 47 children]. AB - OBJECTIVE: To explore the efficacy and safety of the application of enteral nutrition (EN) in gastrointestinal disease in children, and to explore the possibility of the implementation of family EN. METHOD: Retrospective analysis of disease spectrum, EN approach, preparation, speed and time as well as adverse reactions and outcomes in 47 pediatric patients with gastrointestinal disease underwent EN therapy during July 2014 to March 2015. The nutrition indicators before and after EN therapy were compared by paired t-test. RESULT: A total of 47 patients were selected, 27 male (57%) and 20 female (43%), aged 0.8 (0.3, 4.0) years, 9 with mechanical or chemical damage to the esophagus, 7 with inflammatory bowel disease (including ulcerative colitis and Crohn's disease), 6 with chronic diarrhea, 5 with acute pancreatitis, 3 with acute diarrhea and severe malnutrition, 3 with short bowel syndrome, 3 with improper feeding, 3 with feeding difficulties, 3 with protein losing enteropathy, 2 with post-enterostomy, 2 with enterocolitis, 1 with gastroesophageal reflux, were diagnosed. Of 47 cases, 22 were given oral nutrition, 28 were fed with nasogastric tube and 4 with nasojejunal tube feeding, 2 with percutaneous endoscopic gastrojejunostomy tube feeding for each. In these tube-feeding cases, 20 cases were treated with continuous infusion and 21 cases with intermittent infusion. Eleven cases were fed with amino acid formula; 21 cases took the choice of peptide formulations; 16 cases chose whole protein formula, including six cases who chose 3.3-4.2 kJ/ml higher energy density formula, 10 cases selected common energy density formula including breast milk. Twenty-one cases suffered from different degrees of adverse reactions, including vomiting in 7 cases, abdominal pain and bloating in 3, diarrhea in 12, secondary respiratory infections in 5. Five patients were discharged after giving up of treatment by parents due to poor efficacy on primary disease; 3 cases were transferred to other departments for further treatment; 15 cases were discharged with a feeding tube for family nutrition and specialist out-patient treatment. The rest 24 cases were all improved and discharged. There were significant differences in nutrition indicators before and after EN, weight-for-age Z score (WAZ)(-2.3+/-1.9 vs. -1.9+/-1.8, t=4.156, P=0.000), weight-for-height Z score (WHZ)(-1.9+/-1.7 vs. -1.2+/-1.5, t=3.714, P=0.001), albumin ((35+/-9)g/L vs.(39+/-6) g/L, t=3.017, P=0.005) and prealbumin ((0.11+/-0.05)g/L vs.(0.18+/-0.07)g/L, t=5.144, P=0.000). CONCLUSION: EN is suitable for a variety of children's digestive diseases, which can improve the nutritional status of the patients and was safe for clinical application. As the implementation of EN is simple and has good compliance, family EN is proven to be feasible. PMID- 27412740 TI - [Use of P-wave polarity during atrial tachycardia to predict site of origin in children]. AB - OBJECTIVE: To perform a detailed analysis of the P-wave polarity in focal atrial tachycardia (FAT) on the basis of surface electrocardiograms (ECGs) and construct an algorithm for identification of the anatomic site of origin in children. METHOD: P-wave polarities for 40 consecutive children(14 boys and 26 girls, mean age of(8+/-3)years) with FAT undergoing successful radiofrequency ablation of a single atrial focus at First Hospital of Tsinghua University (2009-2014) were analyzed retrospectively from 12-lead ECGs during tachycardia.P waves were classified as positive, negative, isoelectric, or biphasic.The relations between P-wave and anatomic site of origin were analyzed using a chi-square test. RESULT: The P-wave polarities in leads V1(chi(2)=23.509, P=0.000) andI(chi(2)=14.315, P=0.001) were significantly helpful in distinguishing left from right atrial origin of the tachycardia focus.The P-wave in lead V1 of a left atrial tachycardia was always positive or isoelectric in tachycardia.The P-wave in leadIof a right atrial tachycardia was always positive or isoelectric during tachycardia.The P-wave polarities in leads II, III, aVR and aVF(chi(2)=26.447, 23.974, 19.613, 17.415, all P=0.000)distinguished superior from inferior atrial foci significantly.Tachycardia arising from the superior foci (n=22) had positive P waves in leads II, III and aVF ( 95% (n=21), 86% (n=19), 95% (n=21), respectively) and negative P wave in lead aVR (73%, n=16). The P-wave was frequently negative in leads II, III and aVF(n=12) and positive in lead aVR (n=11) for a tachycardia arising from the inferior foci (n=18). The anatomic sites of FAT in children located mainly at right atrial appendage (23%, n=9), coronary sinus (18%, n=7), left atrial appendage (15%, n=6) and right superior pulmonary vein (10%, n=4). CONCLUSION: The anatomic sites of FAT in children are located mainly at right and left atrial appendage, coronary sinus and right superior pulmonary vein.P-waves in leads V1 andIprove to be significantly useful in differentiating left from right atrial tachycardia foci.P-waves in leads II, III, aVR and aVF are helpful in distinguishing superior from inferior atrial foci. PMID- 27412741 TI - [Clinical and electroencephalographic analysis of anti-N-methyl-D-aspartate receptor encephalitis in children]. AB - OBJECTIVE: To study the clinical and electroencephalographic (EEG) characteristics of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) in children. METHOD: Retrospective analysis was performed on the clinical and EEG data of 105 patients with anti-NMDAR encephalitis treated in Beijing Children's Hospital (August 2011-March 2015). Of the 105 patients, 38 were male and 67 were female.The age of onset was from 6 months and 26 days to 15 years and 8 months (average (8+/-4)years). The time for confirmed diagnosis was from 4 days to 850 days (median 24.5 days). According to the modified Rankin scales, the patient's clinical conditions were assessed and underwent continuous EEG (cEEG) monitoring.The data were reviewed and analyzed. RESULT: Based on the severity of the disease, the 105 patients were divided into three groups: mild group (12 cases), moderate group (65 cases), and severe group (28 cases). There were 91 cases(86.7%)with abnormal EEG patterns, including 28 cases (26.7%) with slow background activity in EEG, 25 cases (23.8%) with generalized or diffuse slow waves, 33 cases (31.4%) had focal slow waves, 41 cases (39.0%) had epileptic waves; 10 cases (9.5%) showed unilateral or diffuse alpha-theta band rhythms in nonrapid eye movement (NREM) sleep, 7 cases (6.7%) showed extreme delta brush waves (EDB). Accordingly, the number of patients with abnormal EEG in mild, moderate and severe groups was 5, 58 (89.2%) and 28(100.0%). Seven patients with EDB phenomenon were all in the severe group, and 10 patients with abnormal alpha theta band rhythms were in the moderate group. CONCLUSION: In children with anti NMDAR encephalitis, the EEG patterns are in line with the changes of EEG in general encephalitis.The extent of EEG abnormalities correlates with the clinical severity of the disease. Extreme delta brush and alpha-theta band rhythms may be suggestive of diagnosis and clinical assessment of the disease. PMID- 27412742 TI - [Application of right jugular vessels to build extracorporeal membrane oxygenation for treating the critically ill children]. AB - OBJECTIVE: To summarize the experience in applying a technique of inserting a cannula through right internal jugular vein and common carotid artery to build extracorporeal membrane oxygenation (ECMO) for critically ill children. METHOD: The data of critically ill patients received ECMO support through right internal jugular vein and common carotid artery between December 2011 and December 2015 from Children's Hospital of Fudan University were analyzed retrospectively.The data included diagnosis, age, body weight, time of cannula and ECMO running, complication and prognosis. RESULT: In total 28 patients received ECMO support, 3 patients of post-cardiac surgery with transthoracic cannula were excluded.Twenty five patients inserted cannula through neck vessels were enrolled, 15 boys and 10 girls, the median age was 1.8 years (range, 1 d-13 years), the median weight was 12.0 (2.8-50.0) kg.All the cannula sites were right internal jugular vein and right common carotid artery, before cannula use 5 patients had been inserted central vein tube and 3 patients with blood filter tube in right internal jugular vein, in one case cannula was applied during cardiopulmonary resuscitation.V-A ECMO had been built for all the cases successfully, the median operation time was (45+/-26) min.The pump flow was 80-150 ml/(kg.min), the median duration of ECMO support was 153(14-567) h. Sixteen (64%) patients weaned off ECMO successfully, 15(60%) survived to hospital discharge.About the complication of cannula, six patients developed cannula site bleeding, and two patients required re-fixation of cannula, one patient's external jugular vein had been hurt and sutured for bleeding. CONCLUSION: Application of right jugular vessels to build ECMO is easy and safe for treating the sick children. The skill should be proficient to assure ECMO run and reduce the complications. PMID- 27412743 TI - [Predictive value of upright blood pressure change for long-term prognosis of children with postural tachycardia syndrome treated with midodrine hydrochloride]. AB - OBJECTIVE: To explore the predictive value of upright blood pressure change for long-term prognosis of children with postural tachycardia syndrome (POTS) treated with midodrine hydrochloride. METHOD: A total of 90 children (male 41, female 49) were enrolled in this study. Their mean age was (11.8+/-2.7) years. They were diagnosed as POTS in Peking University First Hospital from 2005 to 2011. According to the upright change of blood pressure at the first visit, they were divided into two groups, effective group (n=55) and ineffective group(n=35). The follow-up time was 53-130 months. The orthostatic intolerance symptom score and symptom free survival rate were compared between the two groups. RESULT: The change of systolic blood pressure and of diastolic blood pressure was lower in effective group than those in ineffective group (0(-6, 0) mmHg (1 mmHg=0.133 kPa) vs. 9(6, 11) mmHg, Z=-8.303, P<0.01; 0(0, 5) mmHg vs. 11(10, 16) mmHg, Z=-7.058, P<0.01). Two groups had no significant difference in symptom scores before treatment((4.8+/-0.9) points vs. (5.0+/-0.8) points, t=-0.53, P=0.595), while symptom scores were lower in effective group than that in ineffective group((1.3+/-0.9) points vs. (4.7+/-0.9) points, t=-15.60, P<0.01 ). The symptom free survival rate was higher in effective group than that in ineffective group (48/55(87.3%) vs. 23/35(65.7%), chi(2)=5.969, P<0.01). CONCLUSION: The upright change of blood pressure has a good predictive value on the long-term survival of POTS children treated with midodrine hydrochloride. PMID- 27412745 TI - [Clinical features and therapy of persistent bacterial bronchitis in 31 children]. AB - OBJECTIVE: To investigate the clinical features and therapy of persistent bacterial bronchitis (PBB). METHOD: A retrospective review of 31 patients with PBB from Octorber 2010 to May 2014 in Department 2 of Respiratory Diseases in Beijing Children's Hospital was undertaken. RESULT: (1) The patients (17 boys and 14 girls) were 6 months to 3 years old. The main complaint was chronic wet cough (>4 weeks); 13 cases had fever and 25 cases had wheezing. Rattle was heard on auscultation in all patients. (2) Chest X ray showed an increase in bronchovascular markings in all cases, accompanied by patchy infiltration in 6 cases. The high resolution computed tomography (HRCT) demonstrated bronchial wall thickening in 25 cases, associated with peri-bronchial patchy infiltration in 18 cases, with organized pneumonia in 7 cases ( atelectasis in 5 cases). Centrilobular nodules and ground-glass opacity were observed in the remaining 6 patients. (3) Purulent secretion was seen in endobronchial cavity by bronchoscopy. Streptococcus pneumoniae was isolated from sputum culture or bronchoalveolar lavage fluid culture in 16 patients. (4)Patients recovered completely after over 2 weeks'treatment with amoxicillin-clavulanate or the second and third generation cephalosporin (including enzyme inhibitors) in 28 cases, carbapenems, teicoplanin , linezolid in 1 case respectively. CONCLUSION: PBB often occurred in 3 years old or younger patients and had chronic wet cough for more than 4 weeks, fever and wheezing. HRCT may reveal bronchial wall thickening, respiratory secretions culture may reveal Streptococcus pneumoniae. Most of patients recovered completely after over 2 weeks'treatment with amoxicillin-clavulanate or the second or third generation cephalosporins (including enzyme inhibitors). PMID- 27412744 TI - [Bronchitis obliterans associated with bronchiolitis obliterans with organizing pneumonia in a child and literature review]. AB - OBJECTIVE: To investigate the clinical-radiologic-pathologic features of bronchitis obliterans that complicated with bronchiolitis obliterans with organizing pneumonia (BOOP). METHOD: The clinical manifestations, characteristic imaging and pathology of a case with pediatric Mycoplasma pneumoniae pneumonia (MPP) complicated with bronchitis obliterans and BOOP were summarized and relative articles were reviewed. RESULT: A 10-year-old girl complained of recurrent paroxysmal cough and episodes of wheezing with exercise, productive of yellowish sputum, irregular fever for 1 month presented with lower breath sounds of left lower lobe and localized tubular breath sounds. Lung imaging studies showed atelectasis of the left lower lobe with proximal bronchiectasis. Follicular hyperplasia of bronchial mucosa, subsegmental bronchial obliterans and sputum bolt were detected via Fiberoptic bronchoscopy. Pathological sections of lung tissue revealed greyish yellow or red color, localized carnification, and yellowish intraluminal excretions. Microscopy displayed fiber connective tissue hyperplasia, foam cells and Masson bodies. Serologic examination detected the titer of MP-IgM antibody over 1?160. Erythromycin, corticosteroids and broncho alveolar lavage were applied to the patient, leading to improved condition for a certain period. However, the symptoms relapsed and surgical resection of left lung had to be carried out to achieve a convalescence eventually. No literature was found from the search results of " Bronchitis obliterans " and " cryptogenic organizing pneumonia" in the China National Knowledge Infrastructure (CNKI) and PubMed database during the period from January 1990 to January 2016. CONCLUSION: The patient who had Bronchitis obliterans complicated with BOOP suffered from persisting fever and respiratory symptoms, and showed lower breath sounds and localized tubular breath sounds. MP-IgM was positive. Lung image showed atelectasis with proximal bronchiectasis. Fiber connective tissue hyperplasia and Masson bodies were found in pathologic examinations. The patient was recovering after surgical resection of the affected side of the lung. PMID- 27412746 TI - [A case of whole arm deletion of chromosome 18p]. PMID- 27412748 TI - [A case of neuronal ceroid lipofuscinosis with MFSD8 gene mutations]. PMID- 27412747 TI - [Clinical analysis of 39 cases who received transplantation of kidney from pediatric organ donors]. AB - OBJECTIVE: To explore the feasibility and clinical significance of pediatric renal transplantation using organ donations from pediatric patients donors. METHOD: Clinical data of children who underwent renal transplantation using organ donations from pediatric patients between September 2011 and December 2014 were retrospectively analyzed, including diagnosis and treatment before transplant, transplant operation, immunosuppression, complication and prognosis. RESULT: Totally 39 cases received pediatric organ donation-pediatric kidney transplantation. The median age at transplantation was 10.5 years. Before transplantation, 37 cases received chronic dialysis. The median waiting time for transplantation was 15 months. The 39 cases received kidneys from 29 donors who were aged from 9 days to 7 years (median 13 months). The median duration of follow-up after the transplantation was 19 months. At 3 month after transplantation and latest follow-up, the length of graft increased (11.3+/-6.4) mm and (17.5+/-10.8) mm, respectively. At 6 month and 12 month after transplantation, the height of the recipients increased (5.8+/-3.5) cm and (15.0+/-3.5) cm, respectively. At latest follow-up, the serum creatinine level was (80.3+/-31.9) MUmol/L and the eGFR was (94.4+/-32.9) ml/(min.1.73 m(2)). The recipient survival rate was 100% and grafts survived in 34 cases; 3 cases lost graft function due to thrombosis of renal vessels and the other 2 cases due to bleeding and chronic allograft nephropathy. Donor age of less than 12 months carried higher risk of thrombosis/hemorrhagic complication (P=0.042) and graft dysfunction (P=0.017). CONCLUSION: Favorable outcome can be obtained from pediatric organ donation-pediatric kidney transplantation. Patient survival rate reached 100% at one-year and three-year graft survival rate was 87%. The size of the allograft would increase and the height of the recipients would improve after transplantation. PMID- 27412749 TI - [Evaluation of glomerular filtration rate in children]. PMID- 27412750 TI - [Recent advance in etiology and pathogenesis of pediatric inflammatory bowel disease]. PMID- 27412751 TI - [Research progress of inflammatory bowel disease and infection]. PMID- 27412752 TI - [A review: the achievement and challenge of artificial placenta]. PMID- 27412753 TI - [Advances in pathogenesis, diagnosis and treatment of complement dysregulation associated atypical hemolytic uremic syndrome]. PMID- 27412754 TI - Safety and Efficacy of Occlusion of Large Extra-Prostatic Anastomoses During Prostatic Artery Embolization for Symptomatic BPH. AB - INTRODUCTION: During PAE, preembolization angiography of the prostatic artery can show large extra-prostatic shunts, at high risk, if embolized, of rectal or penile necrosis. We report our experience with 11 consecutive patients who underwent protective embolization of large extra-prostatic shunts before successful PAE. MATERIALS AND METHODS: We treated 11 consecutive male patients (mean age 67 years), part of a series of 55 consecutive male patients referred for PAE to treat LUTS due to BPH, between December 2013 and January 2015. The procedure involved the exclusion of an extra-prostatic shunt originating from the PA, prior to complete bilateral PAE. We compared the safety and efficacy of the 11 shunt exclusions followed by embolization of the PA to the other 44 basic PAE. Clinical success was defined as a decrease of 25 % or eight points of IPSS, QoL <3 or a one-point decrease, and a Qmax improvement of 25 % or 2.5 mL/s. RESULTS: We had a 100 % rate of occlusion of the anastomosis. Bilateral embolization of the PA was performed in all patients with no additional time of procedure (p = 0.18), but a significant increase of dose area product (p = 0.03). Distal (PErFecTED) embolization was possible in 64 %. There was no worsening of erectile dysfunction, no rectal or penile necrosis, no immediate or late other clinical complications. Clinical success was 91 % (mean follow-up: 3.5 months), compared to 78 % for the entire PAE group. CONCLUSION: PAE using the protection technique in case of large extra-prostatic shunts is as safe and effective as basic procedures and does not induce any additional time of procedure. PMID- 27412755 TI - TACE Combined with Implantation of Irradiation Stent Versus TACE Combine with Bare Stent for HCC Complicated by IVCTT. AB - PURPOSE: This study was designed to evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with intra-IVC implantation of an irradiation stent for the treatment of hepatocellular carcinoma (HCC) complicated by inferior vena cava tumor thrombosis (IVCTT). METHODS: Sixty-one consecutive patients with HCC complicated by IVCTT treated by TACE combined with IVC stenting were retrospectively analysed. IVC stenting was performed using a stent loaded with (125)I seeds strands (the irradiation stent) in 33 patients (Group A) and 28 patients with a bare stent (Group B). Propensity score matching eliminated the baseline differences. Overall survival, oedema related to IVC obstruction remission rate and procedure-related adverse events were compared between the two groups. RESULTS: The adverse effect rate was similar for both Group A and Group B patients, and complications were adequately handled by medical treatment. TACE combined with implantation of an irradiation stent showed a significant median survival benefit over TACE combined with a bare stent, with a median survival time of 203.0 +/- 28.135 days versus 93.0 +/- 24.341 days (p = 0.006). The propensity score-matched (24 pairs) cohort analyses (200 +/- 31.231 days vs. 66 +/- 23.270 days, p = 0.019). The oedema remission rate was 97.0 % in group A patients and 96.4 % in group B, respectively. TACE-irradiation stent and object tumor response were the independent prognostic factors of favorable survival. CONCLUSIONS: TACE combined with irradiation stent implantation is a safe and effective treatment modality for patients with HCC complicated by IVCTT and may extend their survival time. PMID- 27412756 TI - Epidermal growth factor prevents thallium(I)- and thallium(III)-mediated rat pheochromocytoma (PC12) cell apoptosis. AB - We have reported recently that the proliferation of PC12 cells exposed to micromolar concentrations of Tl(I) or Tl(III) has different outcomes, depending on the absence (EGF- cells) or the presence (EGF+ cells) of epidermal growth factor (EGF) added to the media. In the current work, we investigated whether EGF supplementation could also modulate the extent of Tl(I)- or Tl(III)-induced cell apoptosis. Tl(I) and Tl(III) (25-100 MUM) decreased cell viability in EGF- but not in EGF+ cells. In EGF- cells, Tl(I) decreased mitochondrial potential, enhanced H2O2 generation, and activated mitochondrial-dependent apoptosis. In addition, Tl(III) increased nitric oxide production and caused a misbalance between the anti- and pro-apoptotic members of Bcl-2 family. Tl(I) increased ERK1/2, JNK, p38, and p53 phosphorylation in EGF- cells. In these cells, Tl(III) did not affect ERK1/2 and JNK phosphorylation but increased p53 phosphorylation that was related to the promotion of cell senescence. In addition, this cation significantly activated p38 in both EGF- and EGF+ cells. The specific inhibition of ERK1/2, JNK, p38, or p53 abolished Tl(I)-mediated EGF- cell apoptosis. Only when p38 activity was inhibited, Tl(III)-mediated apoptosis was prevented in EGF- and EGF+ cells. Together, current results indicate that EGF partially prevents the noxious effects of Tl by preventing the sustained activation of MAPKs signaling cascade that lead cells to apoptosis and point to p38 as a key mediator of Tl(III)-induced PC12 cell apoptosis. PMID- 27412757 TI - Influence of Staff Encouragement on Perceived Burden of Dietary Restriction Among Patients Living Alone. AB - To help relieve the burden of dietary restrictions experienced by many hemodialysis (HD) patients, dialysis staff may encourage patients, with no consideration to the degree of family support. Here, we clarified the effect of staff encouragement and living conditions on the burden of dietary restrictions in HD patients. This retrospective cohort study was conducted using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) I and III. We enrolled patients aged 18-75 years on HD therapy for at least 3 months. We categorized patients into four groups based on combinations of level of staff encouragement (high or low) and living condition (alone or with family) at baseline survey. Patients who felt they received high staff encouragement and lived with their family were set as the control. The main outcome was increase in patients' perceived burden of dietary restriction after 1 year. 1377 (69.1%) felt they received high staff encouragement, and 176 (9.1%) were living alone. After 1 year, 537 (26.9%) patients reported feeling an increased burden of dietary restriction. A low level of staff encouragement did not increase the burden in any patients, regardless of living situation. However, a high level of staff encouragement did increase the burden in patients living alone (adjusted odds ratio: 1.57, 95% confidence interval: 1.05-2.36). We observed an unexpected association between high staff encouragement and increased burden of dietary restriction among patients living alone. Staff encouragement may not relieve patients' burden with respect to dietary restriction and may in fact exacerbate it. PMID- 27412758 TI - Boron as an Electron-Pair Donor for B???Cl Halogen Bonds. AB - MP2/aug'-cc-pVTZ calculations were performed to investigate boron as an electron pair donor in halogen-bonded complexes (CO)2 (HB):ClX and (N2 )2 (HB):ClX, for X=F, Cl, OH, NC, CN, CCH, CH3 , and H. Equilibrium halogen-bonded complexes with boron as the electron-pair donor are found on all of the potential surfaces, except for (CO)2 (HB):ClCH3 and (N2 )2 (HB):ClF. The majority of these complexes are stabilized by traditional halogen bonds, except for (CO)2 (HB):ClF, (CO)2 (HB):ClCl, (N2 )2 (HB):ClCl, and (N2 )2 (HB):ClOH, which are stabilized by chlorine-shared halogen bonds. These complexes have increased binding energies and shorter B-Cl distances. Charge transfer stabilizes all complexes and occurs from the B lone pair to the sigma* Cl-A orbital of ClX, in which A is the atom of X directly bonded to Cl. A second reduced charge-transfer interaction occurs in (CO)2 (HB):ClX complexes from the Cl lone pair to the pi* C=O orbitals. Equation of-motion coupled cluster singles and doubles (EOM-CCSD) spin-spin coupling constants, 1x J(B-Cl), across the halogen bonds are also indicative of the changing nature of this bond. 1x J(B-Cl) values for both series of complexes are positive at long distances, increase as the distance decreases, and then decrease as the halogen bonds change from traditional to chlorine-shared bonds, and begin to approach the values for the covalent bonds in the corresponding ions [(CO)2 (HB)-Cl]+ and [(N2 )2 (HB)-Cl]+ . Changes in 11 B chemical shieldings upon complexation correlate with changes in the charges on B. PMID- 27412759 TI - Molecular detection of infection homogeneity and impact of miltefosine treatment in a Syrian golden hamster model of Leishmania donovani and L. infantum visceral leishmaniasis. AB - Control of visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani primarily relies on chemotherapy using an increasingly compromised repertoire of antileishmanial compounds. For evaluation of novel drugs, the Syrian golden hamster is considered as a clinically relevant laboratory model. In this study, two molecular parasite detection assays were developed targeting cathepsin-like cysteine protease B (CPB) DNA and 18S rRNA to achieve absolute amastigote quantification in the major target organs liver and spleen. Both quantitative PCR (qPCR) techniques showed excellent agreement with a strong correlation with the conventional microscopic reading of Giemsa-stained tissue smears. Using multiple single tissue pieces and all three detection methods, we confirmed homogeneity of infection in liver and spleen and the robustness of extrapolating whole organ burdens from a small single tissue piece. Comparison of pre- and post-treatment burdens in infected hamsters using the three detection methods consistently revealed a stronger parasite reduction in the spleen compared to the liver, indicating an organ-dependent clearance efficacy for miltefosine. In conclusion, this study in the hamster demonstrated high homogeneity of infection in liver and spleen and advocates the use of molecular detection methods for assessment of low (post-treatment) tissue burdens. PMID- 27412760 TI - Early developmental stages of Ascaris lumbricoides featured by high-resolution mass spectrometry. AB - Ascaris lumbricoides is responsible for a highly disseminated helminth parasitic disease, ascariosis, a relevant parasitosis that responds for great financial burden on the public health system of developing countries. In this work, metabolic fingerprinting using high-resolution mass spectrometry (HRMS) was employed to identify marker molecules from A. lumbricoides in different development stages. We have identified nine biomarkers, such as pheromones and steroidal prohormones in early stages, among other molecules in late development stages, making up four molecules for fertilized eggs, four marker molecules for first larvae (L1) and one marker molecule for third larvae (L3). Therefore, our findings indicate that this approach is suitable for biochemical characterization of A. lumbricoides development stages. Moreover, the straightforward analytical method employed, with almost no sample preparation from a complex matrix (feces) using high-resolution mass spectrometry, suggests that it is possible to seek for an easier and faster way to study animal molding processes. PMID- 27412761 TI - Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3beta and the ERK Pathway. AB - Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H2O2)-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H2O2 exposure led to the increased activities of glycogen synthase kinase 3beta (GSK3beta) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3beta cascade and the ERK pathway induced by H2O2. In addition, both GSK3beta and mitogen-activated protein kinase inhibitors significantly prevented H2O2-induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H2O2-induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H2O2 induced apoptosis via concurrent inhibiting GSK3beta and the ERK pathway in SH SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress. PMID- 27412764 TI - Quantification and classification of substituent effects in organic chemistry: a theoretical molecular electrostatic potential study. AB - Substituent effects in organic chemistry are generally described in terms of experimentally derived Hammett parameters whereas a convenient theoretical tool to study these effects in pi-conjugated molecular systems is molecular electrostatic potential (MESP) analysis. The present study shows that the difference between MESP at the nucleus of the para carbon of substituted benzene and a carbon atom in benzene, designated as DeltaVC, is very useful to quantify and classify substituent effects. On the basis of positive and negative DeltaVC values, a broad classification of around 381 substituents into electron withdrawing and donating categories is made. Each category is again sorted based on the magnitude of DeltaVC into subcategories such as very strong, strong, medium, and weak electron donating/withdrawing. Furthermore, the data are used to show the transferability and additivity of substituent effects in pi-conjugated organic molecules such as condensed aromatic, olefinic, acetylenic, and heterocyclic systems. The transferability properties hold good for DeltaVC in all these molecular systems. The additive properties of substituent effects are strongly reflected on DeltaVC and the predictive power of the data to assign the total substituent effects of multi-substituted systems is verified. The DeltaVC data and the present classification of substituents are very useful to design pi conjugated organic molecular systems with desired electron rich/poor character. PMID- 27412762 TI - High Sensitivity Crosslink Detection Coupled With Integrative Structure Modeling in the Mass Spec Studio. AB - The Mass Spec Studio package was designed to support the extraction of hydrogen deuterium exchange and covalent labeling data for a range of mass spectrometry (MS)-based workflows, to integrate with restraint-driven protein modeling activities. In this report, we present an extension of the underlying Studio framework and provide a plug-in for crosslink (XL) detection. To accommodate flexibility in XL methods and applications, while maintaining efficient data processing, the plug-in employs a peptide library reduction strategy via a presearch of the tandem-MS data. We demonstrate that prescoring linear unmodified peptide tags using a probabilistic approach substantially reduces search space by requiring both crosslinked peptides to generate sparse data attributable to their linear forms. The method demonstrates highly sensitive crosslink peptide identification with a low false positive rate. Integration with a Haddock plug-in provides a resource that can combine multiple sources of data for protein modeling activities. We generated a structural model of porcine transferrin bound to TbpB, a membrane-bound receptor essential for iron acquisition in Actinobacillus pleuropneumoniae Using mutational data and crosslinking restraints, we confirm the mechanism by which TbpB recognizes the iron-loaded form of transferrin, and note the requirement for disparate sources of restraint data for accurate model construction. The software plugin is freely available at www.msstudio.ca. PMID- 27412763 TI - Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos. AB - PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development. PMID- 27412765 TI - Relationship between blood lactate and cortical excitability between taekwondo athletes and non-athletes after hand-grip exercise. AB - OBJECTIVES: In taekwondo competitions, fatigue has a large influence on performance. Recent studies have reported that the excitability in the primary hand motor cortex, investigated with transcranial magnetic stimulation (TMS), is enhanced at the end of a maximal exercise and that this improvement correlates with blood lactate. The aim of the present study was to investigate the relationship between blood lactate and cortical excitability in taekwondo athletes and non-athletes. METHODS: The excitability of the primary motor cortex was measured before and after fatiguing hand-grip exercise by TMS. Capillary blood lactate was measured at rest (pre-test), at the end (0 min), and at 3 and 10 min after the exercise by using a "Lactate Pro" portable lactate analyzer. RESULTS: Significant differences in cortical excitability between the two groups were found after the exercise (p < 0.05). Furthermore, we found a significant relationship between cortical excitability and blood lactate (p < 0.01). CONCLUSION: The present findings showed changes in the excitability in the athletes group and also in the non-athletes group. However, blood lactate seems to have the greater effect in trained subjects compared to untrained subjects. In fact, it appears that, during extremely intensive exercise in taekwondo athletes, lactate may delay the onset of fatigue not only by maintaining the excitability of muscle, but also by increasing the excitability of the primary motor cortex more than in non-athletes. PMID- 27412767 TI - Role of CREB on heme oxygenase-1 induction in adrenal cells: involvement of the PI3K pathway. AB - In addition to the well-known function of ACTH as the main regulator of adrenal steroidogenesis, we have previously demonstrated its effect on the transcriptional stimulation of HO-1 expression, a component of the cellular antioxidant defense system. In agreement, we hereby demonstrate that, in adrenocortical Y1 cells, HO-1 induction correlates with a significant prevention of the generation of reactive oxygen species induced by H2O2/Fe(2+) ACTH/cAMP dependent activation of redox-imbalanced related factors such as NRF2 or NFkappaB and the participation of MAPKs in this mechanism was, however, discarded based on results with specific inhibitors and reporter plasmids. We suggest the involvement of CREB in HO-1 induction by ACTH/cAMP, as transfection of cells with a dominant-negative isoform of CREB (DN-CREB-M1) decreased, while overexpression of CREB increased HO-1 protein levels. Sequence screening of the murine HO-1 promoter revealed CRE-like sites located at -146 and -37 of the transcription start site and ChIP studies indicated that this region recruits phosphorylated CREB (pCREB) upon cAMP stimulation in Y1 cells. In agreement, H89 (PKA inhibitor) or cotransfection with DN-CREB-M1 prevented the 8Br-cAMP-dependent increase in luciferase activity in cells transfected with pHO-1[-295/+74].LUC. ACTH and cAMP treatment induced the activation of the PI3K/Akt signaling pathway in a PKA independent mechanism. Inhibition of this pathway prevented the cAMP-dependent increase in HO-1 protein levels and luciferase activity in cells transfected with pHO-1[-295/+74].LUC. Finally, here we show a crosstalk between the cAMP/PKA and PI3K pathways that affects the binding of p-CREB to its cognate element in the murine promoter of the Hmox1 gene. PMID- 27412766 TI - Physiological cerebrovascular remodeling in response to chronic mild hypoxia: A role for activated protein C. AB - Activated protein C (APC) is a serine protease that promotes favorable changes in vascular barrier integrity and post-ischemic angiogenic remodeling in animal models of ischemic stroke, and its efficacy is currently being investigated in clinical ischemic stroke trials. Interestingly, application of sub-clinical chronic mild hypoxia (CMH) (8% O2) also promotes angiogenic remodeling and increased tight junction protein expression, suggestive of enhanced blood-brain barrier (BBB) integrity, though the role of APC in mediating the influence of CMH has not been investigated. To examine this potential link, we studied CMH-induced cerebrovascular remodeling after treating mice with two different reagents: (i) a function-blocking antibody that neutralizes APC activity, and (ii) exogenous recombinant murine APC. While CMH promoted endothelial proliferation, increased vascular density, and upregulated the angiogenic endothelial integrins alpha5beta1 and alphavbeta3, these events were almost completely abolished by functional blockade of APC. Consistent with these findings, addition of exogenous recombinant APC enhanced CMH-induced endothelial proliferation, expansion of total vascular area and further enhanced the CMH-induced right-shift in vessel size distribution. Taken together, our findings support a key role for APC in mediating physiological remodeling of cerebral blood vessels in response to CMH. PMID- 27412769 TI - (1)H, (15)N, (13)C resonance assignments for pyrazinoic acid binding domain of ribosomal protein S1 from Mycobacterium tuberculosis. AB - Ribosomal protein S1 of Mycobacterium tuberculosis (MtRpsA) binds to ribosome and mRNA, and plays significant role in the regulation of translation initiation, conventional protein synthesis and transfer-messenger RNA (tmRNA) mediated trans translation. It has been identified as the target of pyrazinoic acid (POA), a bactericidal moiety from hydrolysis of pyrazinamide, which is a mainstay of combination therapy for tuberculosis. POA prevented the interactions between the C-terminal S1 domain of MtRpsA (residues 280-368, MtRpsA(CTD)_S1) and tmRNA; so that POA can inhibit the trans-translation, which is a key component of multiple quality control pathways in bacteria. However, the details of molecular mechanism and dynamic characteristics for MtRpsA(CTD)_S1 interactions with POA, tmRNA or mRNA are still unclear. Here we present the (1)H, (15)N, (13)C resonance assignments of MtRpsA(CTD)_S1 as well as the secondary structure information based on backbone chemical shifts, which lay foundation for further solution structure determination, dynamic properties characterization and interactions investigation between MtRpsA(CTD)_S1 and tmRNA, RNA or POA. PMID- 27412771 TI - Institutional core facilities: prerequisite for breakthroughs in the life sciences: Core facilities play an increasingly important role in biomedical research by providing scientists access to sophisticated technology and expertise. PMID- 27412770 TI - Dynamic studies of H-Ras*GTPgammaS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution. AB - The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras?GTPgammaS mixed with a functional fragment of Sos (Sos(Cat)) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras?GTPgammaS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of Sos(Cat), while Sos(Cat) also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras?GTPgammaS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras?GTPgammaS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP -> GTP exchange reaction, but also explains measurable GTP -> GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos. PMID- 27412772 TI - Analysis of Serum microRNA Profile by Solexa Sequencing in Women With Endometriosis. AB - OBJECTIVES: The potential roles of serum microRNAs (miRNAs), as biomarkers, in noninvasive diagnosis of endometriosis have been reported by microarray analysis. However, microarray analysis cannot perform well in outcome accuracy and repeatability and is not suitable to be used for exploring new targets. Here, Solexa sequencing, a wide and precise method, was adopted to further analyze the serum miRNAs profile in endometriosis, which may offer more evidence to apply serum miRNAs as biomarkers in diagnosis of endometriosis. MATERIALS AND METHODS: Serum samples were collected from 30 patients with minimal-mild endometriosis and 20 women without endometriosis as control. Expression of serum miRNAs was measured by Solexa sequencing and validated by quantitative real-time polymerase chain reaction (qPCR). RESULTS: Solexa sequencing showed 93.63% clean readouts for all small RNAs in the serum of patients with endometriosis and controls. A total of 108 miRNAs were found to be differentially expressed in the serum of patients with endometriosis by deep sequencing, compared to controls. Among them, 98 miRNAs were significantly downregulated, while 10 miRNAs were significantly upregulated. Only 21 of 98 significantly downregulated miRNAs, and none of significantly upregulated miRNAs were reported in published literatures, which may be due to the differences in samples and analytical methods. The Solexa sequencing results were consequently validated by qPCR in additional samples. Some miRNAs were identified to be promising diagnostic markers of endometriosis. The functional annotation of target genes revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that a majority of differential miRNAs might be involved in endometriosis. CONCLUSION: Circulating miRNAs may be useful as detection biomarkers for the early diagnosis of minimal mild endometriosis. PMID- 27412773 TI - Decidualization Differentially Regulates microRNA Expression in Eutopic and Ectopic Endometrial Stromal Cells. AB - Decidualization of the endometrium and endometriosis involves the morphological and biochemical reprogramming of the estrogen-primed proliferative stromal compartment under the continuing influence of progesterone. Here, we evaluated the involvement of microRNA in the decidualization processes of normal endometrial stromal cells (NESCs) and endometriotic cyst stromal cells (ECSCs). In vitro decidualization of NESCs and ECSCs was induced by long-term culture with a combination of 0.5 mmol/L of dibutyryl cyclic adenosine monophosphate and 100 nmol/L of dienogest. We investigated the effect of in vitro decidualization on the microRNA and messenger RNA (mRNA) expression profiles of the NESCs and ECSCs using global microarray techniques and an Ingenuity Pathways Analysis. Decidualization differentially enhanced the miR-30a-5p expression in the NESCs and the miR-210 expression in the ECSCs. The enhanced miR-30a-5p expression in the NESCs correlated with the increased mRNA expression of Kruppel-like factor 9 and period circadian clock 3 as well as the decreased mRNA expression of tolloid like 1, tolloid-like 2, and paired-like homeodomain 1. The enhanced expression of miR-210 in the ECSCs correlated with the decreased mRNA expression of growth hormone receptor and thymidine kinase 1. Although there is no direct evidence, we speculate that the loss of miR-30a-5p-mediated mechanisms of decidualization and the acquisition of miR-210-mediated mechanisms of decidualization may be involved in the progesterone resistance in endometriosis. Further investigations are necessary to test this speculation. PMID- 27412774 TI - What do we know about mobile applications for diabetes self-management? A review of reviews. AB - Diabetes is a chronic illness with significant health consequences, especially for those who are unable to adhere to the complex treatment regimen. Self management tasks such as regular medication and insulin use, frequent blood sugar checks, strict diet management, and consistent exercise can be quite challenging. Mobile technologies, specifically mobile applications (apps), present a unique opportunity to help patients improve adherence to these behaviors. The availability of commercial diabetes self-management apps is increasing rapidly, making it difficult for patients and providers to stay informed about app options. A number of reviews have described commercial app technology and use for patients with diabetes. The aims of this article are to summarize the results and themes of those reviews, to review outcomes of apps described in the research literature, and to identify areas for further consideration in the use of mobile apps for diabetes self-management. PMID- 27412775 TI - Imagining roles for epigenetics in health promotion research. AB - Discoveries from the Human Genome Project have invigorated discussions of epigenetic effects-modifiable chemical processes that influence DNA's ability to give instructions to turn gene expression on or off-on health outcomes. We suggest three domains in which new understandings of epigenetics could inform innovations in health promotion research: (1) increase the motivational potency of health communications (e.g., explaining individual differences in health outcomes to interrupt optimistic biases about health exposures); (2) illuminate new approaches to targeted and tailored health promotion interventions (e.g., relapse prevention targeted to epigenetic responses to intervention participation); and (3) inform more sensitive measures of intervention impact, (e.g., replace or augment self-reported adherence). We suggest a three-step process for using epigenetics in health promotion research that emphasizes integrating epigenetic mechanisms into conceptual model development that then informs selection of intervention approaches and outcomes. Lastly, we pose examples of relevant scientific questions worth exploring. PMID- 27412776 TI - Acculturation and bicultural efficacy effects on Chinese American immigrants' diabetes and health management. AB - The primary goal of this study was to examine effects of bicultural efficacy, or perceived confidence in dealing with bicultural acculturation stressors, on type 2 diabetes management and health for first-generation, Cantonese-speaking, Chinese American immigrants (N = 162) recruited for a larger community-based diabetes intervention study (Chesla et al. in Res Nurs Health 36(4):359-372, 2013. doi: 10.1002/nur.21543 ). The current study also tested whether a new Bicultural Efficacy in Health Management (BEFF-HM) scale is a more robust predictor of diabetes and health outcomes than proxy (years in the U.S.) and general acculturation measures. Hierarchical regression analyses of cross sectional data revealed that high BEFF-HM was significantly related to positive outcomes on five of six diabetes and health measures as hypothesized after accounting for participant characteristics, proxy and general acculturation measures, and social support. Proxy and general acculturation measures failed to predict any study outcome supporting our secondary hypothesis that BEFF-HM is a better predictor of Chinese American immigrants' diabetes and health management. An immigrant-focused research approach advances understanding of acculturation and bicultural efficacy effects on health by identifying key acculturation domains for study. PMID- 27412777 TI - The evolution of adult light emission color in North American fireflies. AB - Firefly species (Lampyridae) vary in the color of their adult bioluminescence. It has been hypothesized that color is selected to enhance detection by conspecifics. One mechanism to improve visibility of the signal is to increase contrast against ambient light. High contrast implies that fireflies active early in the evening will emit yellower luminescence to contrast against ambient light reflected from green vegetation, especially in habitats with high vegetation cover. Another mechanism to improve visibility is to use reflection off the background to enhance the light signal. Reflectance predicts that sedentary females will produce greener light to maximize reflection off the green vegetation on which they signal. To test these predictions, we recorded over 7500 light emission spectra and determined peak emission wavelength for 675 males, representing 24 species, at 57 field sites across the Eastern United States. We found support for both hypotheses: males active early in more vegetated habitats produced yellower flashes in comparison to later-active males with greener flashes. Further, in two of the eight species with female data, female light emissions were significantly greener as compared to males. PMID- 27412778 TI - Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution. AB - Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction >=20 % relative and >=5 % absolute) and non responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression. PMID- 27412779 TI - Preoperative Plasma Aldosterone Levels and Postoperative Atrial Fibrillation Occurrence Following Cardiac Surgery: A Review of Literature and Design of the ALDO-POAF Study (ALDOsterone for Prediction of Post-Operative Atrial Fibrillation). AB - BACKGROUND: Post-operative atrial fibrillation (POAF) is a major and frequent complication occurring after cardiac surgery, contributing to prolonged intensive care and hospital stays and is associated with several cardiovascular complications. The exact mechanisms and signaling pathways involved in the development of POAF seem to be multifactorial and remain to date incompletely understood. beta-blockers and amiodarone are the first line preventive drugs but are partially effective and near 30% of POAF resist to these strategies. OBJECTIVE AND METHOD: In this work, we review the current knowledge about pathophysiological POAF mechanisms and preventive pharmacological strategies. We also discuss the rational for the use of pre-operative plasma aldosterone and galectin-3 (Gal-3) levels as predictive biomarkers of POAF and the potential role of aldosterone antagonists in the POAF preventive strategy. CONCLUSION: POAF is a major complication occurring after cardiac surgery. In this context, there is some evidence indicating that renin-angiotensin-aldosterone system and Gal-3 could be very useful predictive biomarkers of POAF and potentially interesting therapeutic target to prevent POAF occurrence. We present the rationale and the design of the ALDO-POAF trial (ALDOsterone for prediction of Post- Operative Atrial Fibrillation, NCT 02814903). PMID- 27412780 TI - Waking up in the zone with Sleep Cycle. PMID- 27412781 TI - Author response to the letter from Dr Hewett. PMID- 27412782 TI - The workload-injury aetiology model. PMID- 27412784 TI - Moving at the speed of science: Regulatory flexibility for unmet medical needs. PMID- 27412783 TI - Reduced amygdala responsivity during conditioning to trauma-related stimuli in posttraumatic stress disorder. AB - Exaggerated conditioned fear responses and impaired extinction along with amygdala overactivation have been observed in posttraumatic stress disorder (PTSD). These fear responses might be triggered by cues related to the trauma through higher-order conditioning, where reminders of the trauma may serve as unconditioned stimuli (US) and could maintain the fear response. We compared arousal, valence, and US expectancy ratings and BOLD brain responses using fMRI in 14 traumatized persons with PTSD and 14 without PTSD (NPTSD) and 13 matched healthy controls (HC) in a differential aversive conditioning paradigm. The US were trauma-specific pictures for the PTSD and NPTSD group and equally aversive and arousing for the HC; the conditioned stimuli (CS) were graphic displays. During conditioning, the PTSD patients compared to the NPTSD and HC indicated higher arousal to the conditioned stimulus that was paired with the trauma picture (CS+) compared to the unpaired (CS-), increased dissociation during acquisition and extinction, and failure to extinguish the CS/US-association compared to NPTSD. During early and late acquisition, the PTSD patients showed a significantly lower amygdala activation to CS+ versus CS- and a negative interaction between activation in the amygdala and dorsolateral prefrontal cortex (PFC), while NPTSD and HC displayed a negative interaction between amygdala and medial PFC. These findings suggest maladaptive anticipatory coping with trauma related stimuli in patients with PTSD, indicated by enhanced conditioning, with related abnormal amygdala reactivity and connectivity, and delayed extinction. PMID- 27412785 TI - Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. AB - C9ORF72 mutations are found in a significant fraction of patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia, yet the function of the C9ORF72 gene product remains poorly understood. We show that mice harboring loss-of-function mutations in the ortholog of C9ORF72 develop splenomegaly, neutrophilia, thrombocytopenia, increased expression of inflammatory cytokines, and severe autoimmunity, ultimately leading to a high mortality rate. Transplantation of mutant mouse bone marrow into wild-type recipients was sufficient to recapitulate the phenotypes observed in the mutant animals, including autoimmunity and premature mortality. Reciprocally, transplantation of wild-type mouse bone marrow into mutant mice improved their phenotype. We conclude that C9ORF72 serves an important function within the hematopoietic system to restrict inflammation and the development of autoimmunity. PMID- 27412787 TI - Noninvasive high-intensity focused ultrasound treatment of twin-twin transfusion syndrome: A preliminary in vivo study. AB - We investigated the efficacy, maternofetal responses, and safety of using high intensity focused ultrasound (HIFU) for noninvasive occlusion of placental vasculature compared to sham treatment in anesthetized pregnant sheep. This technique for noninvasive occlusion of placental vasculature may be translatable to the treatment of conditions arising from abnormal placental vasculature, such as twin-twin transfusion syndrome (TTTS). Eleven pregnant sheep were instrumented with maternal and fetal arterial catheters and time-transit flow probes to monitor cardiovascular, acid-base, and metabolic status, and then exposed to HIFU (n = 5) or sham (n = 6) ablation of placental vasculature through the exposed uterine surface. Placental vascular flow was occluded in 28 of 30 targets, and histological examination confirmed occlusion in 24 of 30 targets. In both HIFU and sham exposures, uterine contact reduced maternal uterine artery flow, but delivery of oxygen and glucose to the fetal brain remained normal. HIFU can consistently occlude in vivo placental vessels and ablate blood flow in a pregnant sheep model. Cardiovascular and metabolic fetal responses suggest that the technique is safe in the short term and potentially translatable to human pregnancy. PMID- 27412786 TI - An miRNA-mediated therapy for SCA6 blocks IRES-driven translation of the CACNA1A second cistron. AB - Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by slowly progressive ataxia and Purkinje cell degeneration. SCA6 is caused by a polyglutamine repeat expansion within a second CACNA1A gene product, alpha1ACT. alpha1ACT expression is under the control of an internal ribosomal entry site (IRES) present within the CACNA1A coding region. Whereas SCA6 allele knock-in mice show indistinguishable phenotypes from wild type littermates, expression of SCA6-associated alpha1ACT (alpha1ACTSCA6) driven by a Purkinje cell-specific promoter in mice produces slowly progressive ataxia and cerebellar atrophy. We developed an early-onset SCA6 mouse model using an adeno-associated virus (AAV)-based gene delivery system to ectopically express CACNA1A IRES-driven alpha1ACTSCA6 to test the potential of CACNA1A IRES-targeting therapies. Mice expressing AAV9-mediated CACNA1A IRES-driven alpha1ACTSCA6 exhibited early-onset ataxia, motor deficits, and Purkinje cell degeneration. We identified miR-3191-5p as a microRNA (miRNA) that targeted CACNA1A IRES and preferentially inhibited the CACNA1A IRES-driven translation of alpha1ACT in an Argonaute 4 (Ago4)-dependent manner. We found that eukaryotic initiation factors (eIFs), eIF4AII and eIF4GII, interacted with the CACNA1A IRES to enhance alpha1ACT translation. Ago4-bound miR-3191-5p blocked the interaction of eIF4AII and eIF4GII with the CACNA1A IRES, attenuating IRES-driven alpha1ACT translation. Furthermore, AAV9-mediated delivery of miR-3191-5p protected mice from the ataxia, motor deficits, and Purkinje cell degeneration caused by CACNA1A IRES driven alpha1ACTSCA6 We have established proof of principle that viral delivery of an miRNA can rescue a disease phenotype through modulation of cellular IRES activity in a mouse model. PMID- 27412788 TI - Tunable dark plasmons in a metallic nanocube dimer: toward ultimate sensitivity nanoplasmonic sensors. AB - Metallic nanoparticles can function as label-free nanosensors monitoring the local dielectric environment in their close vicinity, thanks to the localized surface plasmon resonances. The sensing figure of merit is limited by the total loss rate of the plasmon. Here, we theoretically study a silver nanocube dimer and discover for the first time a dark plasmon with its total loss rate at the lower theoretical limit. It originates from the attractive coupling of the dipolar and quadrupolar mode in the individual nanocubes. It shows an unprecedented sensitivity to the interparticle gap distance, i.e., one angstrom change in the gap distance results in a shift twice as large as the peak width. The sensing figure of merit using this dark plasmon is 56-61, reaching the ultimate value limited only by the material permittivity. The field of the mode is confined mainly within the gap region which is in the extreme deep subwavelength (3.5 * 10(-6)lambda0(3)) region. Besides sensing applications, the dark plasmon also shows foreseeable potential in enhanced spectroscopy, nanolasers and other nanophotonic devices. PMID- 27412789 TI - Dopaminergic receptor blockade changes a functional connectivity network centred on the amygdala. AB - Resting-state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro-psychiatric conditions. One approach that has recently gained prominence in this regard-and which we use in this study-is to investigate how resting-state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2-receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network-based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2-receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting-state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment. Hum Brain Mapp 37:4148 4157, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27412791 TI - Natural Product Splicing Inhibitors: A New Class of Antibody-Drug Conjugate (ADC) Payloads. AB - There is a considerable ongoing work to identify new cytotoxic payloads that are appropriate for antibody-based delivery, acting via mechanisms beyond DNA damage and microtubule disruption, highlighting their importance to the field of cancer therapeutics. New modes of action will allow a more diverse set of tumor types to be targeted and will allow for possible mechanisms to evade the drug resistance that will invariably develop to existing payloads. Spliceosome inhibitors are known to be potent antiproliferative agents capable of targeting both actively dividing and quiescent cells. A series of thailanstatin-antibody conjugates were prepared in order to evaluate their potential utility in the treatment of cancer. After exploring a variety of linkers, we found that the most potent antibody-drug conjugates (ADCs) were derived from direct conjugation of the carboxylic acid containing payload to surface lysines of the antibody (a "linker-less" conjugate). Activity of these lysine conjugates was correlated to drug-loading, a feature not typically observed for other payload classes. The thailanstatin conjugates were potent in high target expressing cells, including multidrug resistant lines, and inactive in nontarget expressing cells. Moreover, these ADCs were shown to promote altered splicing products in N87 cells in vitro, consistent with their putative mechanism of action. In addition, the exposure of the ADCs was sufficient to result in excellent potency in a gastric cancer xenograft model at doses as low as 1.5 mg/kg that was superior to the clinically approved ADC T DM1. The results presented herein therefore open the door to further exploring splicing inhibition as a potential new mode-of-action for novel ADCs. PMID- 27412790 TI - Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients. AB - Human noroviruses (HuNoVs) can often cause chronic infections in solid organ and haematopoietic stem cell transplant (HSCT) patients. Based on histopathological changes observed during HuNoV infections, the intestine is the presumed site of virus replication in patients; however, the cell types infected by HuNoVs remain unknown. The objective of this study was to characterize histopathological changes during HuNoV infection and to determine the cell types that may be permissive for HuNoV replication in transplant patients. We analysed biopsies from HuNoV-infected and non-infected (control) transplant patients to assess histopathological changes in conjunction with detection of HuNoV antigens to identify the infected cell types. HuNoV infection in immunocompromised patients was associated with histopathological changes such as disorganization and flattening of the intestinal epithelium. The HuNoV major capsid protein, VP1, was detected in all segments of the small intestine, in areas of biopsies that showed histopathological changes. Specifically, VP1 was detected in enterocytes, macrophages, T cells and dendritic cells. HuNoV replication was investigated by detecting the non-structural proteins, RdRp and VPg. We detected RdRp and VPg along with VP1 in duodenal and jejunal enterocytes. These results provide critical insights into histological changes due to HuNoV infection in immunocompromised patients and propose human enterocytes as a physiologically relevant cell type for HuNoV cultivation. PMID- 27412793 TI - Erratum. PMID- 27412792 TI - Issue Cover (August 2016). AB - Cover legend: Absence of the novel endolysosomal trafficking regulator WDR81 (green) induces the accumulation of tetherin (red) in enlarged early endosomes. WDR81 knock-out HeLa cells were genetically complemented with an HA-tagged WDR81 construct and imaged by confocal immunofluorescence microscopy. The original image was processed with photo editing software and overlaid with artistic effects. See Rapiteanu et al. Traffic 2016; 17(8):940-958. Read the full article on doi: 10.1111/tra.12409. PMID- 27412794 TI - Carbon nanohorns allow acceleration of osteoblast differentiation via macrophage activation. AB - Carbon nanohorns (CNHs), formed by a rolled graphene structure and terminating in a cone, are promising nanomaterials for the development of a variety of biological applications. Here we demonstrate that alkaline phosphatase activity is dramatically increased by coculture of human monocyte derived macrophages (hMDMs) and human mesenchymal stem cells (hMSCs) in the presence of CNHs. CNHs were mainly localized in the lysosome of macrophages more than in hMSCs during coculturing. At the same time, the amount of Oncostatin M (OSM) in the supernatant was also increased during incubation with CNHs. Oncostatin M (OSM) from activated macrophage has been reported to induce osteoblast differentiation and matrix mineralization through STAT3. These results suggest that the macrophages engulfed CNHs and accelerated the differentiation of mesenchymal stem cells into the osteoblast via OSM release. We expect that the proof-of-concept on the osteoblast differentiation capacity by CNHs will allow future studies focused on CNHs as ideal therapeutic materials for bone regeneration. PMID- 27412795 TI - A new modified blood pressure-to-height ratio simplifies the screening of hypertension in Han Chinese children. AB - The present study evaluated the simplicity and accuracy of a new modified blood pressure-to-height ratio (MBPHR3) in identifying hypertension among Han children aged 7-12 years. In 2011, anthropometric measurements were collected as part of a cross-sectional population-based study of 1352 Han children aged 7-12 years. Receiver operating characteristic curve analyses were performed to assess the accuracy of the modified systolic blood pressure-to-height ratio (MSBPHR3) and the modified diastolic blood pressure-to-height ratio (MDBPHR3) as diagnostic tests for the detection of elevated SBP and DBP, respectively. The accuracies of MSBPHR3 and MDBPHR3 (as assessed by the area under the curve) in identifying elevated SBP and DBP were greater than 0.85 (0.974-0.995). When the MBPHR3 was used to identify hypertensive children, the sensitivity was 100% in boys and 100% in girls. The specificity was 93.8% in boys and 97.1% in girls. In conclusion, the MBPHR3 is a simple, accurate and non-age-dependent index for the screening of hypertension in Han children. PMID- 27412798 TI - A modified DASH diet is one possible solution for overcoming the unfavorable link between vegetable and salt intake in the Japanese diet. PMID- 27412796 TI - Effects of the DASH-JUMP dietary intervention in Japanese participants with high normal blood pressure and stage 1 hypertension: an open-label single-arm trial. AB - The Dietary Approaches to Stop Hypertension (DASH) diet is recommended by the American Heart Association to lower blood pressure (BP); however, its effects in Japanese participants have not been rigorously studied. We assessed the effects of the DASH-Japan Ube Modified diet Program (DASH-JUMP), a modified DASH diet, on cardiometabolic and inflammatory biomarkers in Japanese participants with untreated high-normal BP or stage 1 hypertension. Fifty-eight participants (30 men and 28 women; mean age 54.1+/-8.1 years) with untreated high-normal BP or stage 1 hypertension followed the DASH-JUMP (salt 8.0 g per day) for 2 months. After the intervention period, they resumed their usual diets for 4 months. The DASH-JUMP significantly decreased the participants' body mass index values (24.6+/-3.5 kg m-2 at baseline?23.2+/-3.3 kg m-2 at 2 months, P=0.000), BP (153+/ 14/91+/-11 mm Hg at baseline?130+/-16/80+/-9 mm Hg at 2 months, P=0.000 and 139+/ 16/85+/-10 mm Hg at 6 months, P=0.000), fasting serum glucose level (100+/-26 mg dl-1?94+/-15 mg dl-1 at 2 months, P=0.003) and fasting insulin level (6.9+/-5.9 MUIU ml-1?4.4+/-2.7 MUIU ml-1 at 2 months, P=0.000). The mean compliance of the participants for the DASH-JUMP diet was 88.5%. The DASH-JUMP diet reduced cardiovascular risk factors and may be an effective nutritional strategy for preventing cardiovascular events. PMID- 27412797 TI - New semiquantitative ultrasonographic score for peripheral arterial disease assessment and its association with cardiovascular risk factors. AB - The data concerning the distribution, extent and progression of peripheral arterial disease (PAD), as well as its association with traditional cardiovascular (CV) risk factors, have generally been obtained from studies of patients in advanced stages of the disease undergoing surgical or endovascular treatment. In this study, we have introduced a new semiquantitative ultrasonographic score (ultrasonographic lower limb atherosclerosis (ULLA) score) that is able to categorize lower limb atherosclerotic lesions at all stages of PAD. We then associated these ultrasonographic categories with a CV risk profile. We enrolled 320 consecutive subjects with symptoms suggestive of PAD or with known CV risk factors referring to our angiology unit between 1 July 2014 and 30 June 2015 for ultrasonographic evaluation of the lower limb arteries. Femoropopliteal and run-off segments were categorized together and separately based on their ultrasonographic characteristics. In univariate and multivariate analyses, the ULLA scores were significantly associated with the main CV risk factors, that is, age, male gender, cigarette smoking, arterial hypertension, diabetes, dyslipidemia, sedentary lifestyle, previous CV events and family history of CV disease, and also confirming the specific association of single risk factors with different segments of lower limb arteries. The proposed ULLA score enables a complete evaluation of the entire lower limb atherosclerotic burden, extending the results concerning the association of PAD with CV risk factors to all stages of the disease, including the early stages. It can be feasible that this new score will facilitate better evaluation of the progression of PAD and its prospective role in CV risk stratification. PMID- 27412799 TI - Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats. AB - Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases. PMID- 27412801 TI - Transplantation in alcohol-induced liver diseases-a kind of gene therapy for addictive behaviour? PMID- 27412802 TI - The nutrition and food-related roles, experiences and support needs of female family carers of malnourished older rehabilitation patients. AB - BACKGROUND: To improve perceived value of nutrition support and patient outcomes, the present study aimed to determine the nutrition and food-related roles, experiences and support needs of female family carers of community-dwelling malnourished older adults admitted to rehabilitation units in rural New South Wales, Australia, both during admission and following discharge. METHODS: Four female family carers of malnourished rehabilitation patients aged >=65 years were interviewed during their care-recipients' rehabilitation admission and again at 2 weeks post-discharge. The semi-structured interviews were audiotaped, transcribed and analysed reflecting an interpretative phenomenological approach by three researchers. A series of 'drivers' relevant to the research question were agreed upon and discussed. RESULTS: Three drivers were identified. 'Responsibility' was related to the agency who assumed responsibility for providing nutrition support and understanding family carer obligation to provide nutrition support. 'Family carer nutrition ethos' was related to how carer nutrition beliefs, knowledge and values impacted the nutrition support they provided, the high self-efficacy of family carers and an incongruence with an evidence-based approach for treating malnutrition. 'Quality of life' was related to the carers' focus upon quality of life as a nutrition strategy and outcome for their care-recipients, as well as how nutrition support impacted upon carer burden. CONCLUSIONS: Rehabilitation units and rehabilitation dietitians should recognise and support family carers of malnourished patients, which may ultimately lead to an improved perceived benefit of care and patient outcomes. Intervention research is required to make strong recommendations for practice. PMID- 27412803 TI - Referral for Adolescent Idiopathic Scoliosis by Pediatric Primary Care Providers. AB - This study sought to examine primary care physician opinions regarding referral practices for patients with adolescent idiopathic scoliosis (AIS) and to determine if curve severity at the time of referral is correlated with insurance status. A survey was distributed to pediatric primary care providers to determine referral practices. A chart review of patients referred to a pediatric spine specialist for AIS was performed. A total of 59.3% of respondents stated their referral threshold for AIS patients was <20 degrees . The mean curve size in privately insured patients was 27 degrees (range 6 degrees -68 degrees ), whereas the mean curve size in the publicly insured group was 27.6 degrees (range = 6 degrees -58 degrees ; P = .9). Large disparities among referral practices exist among pediatric primary care providers, although insurance status did not seem to affect curve size at the time of referral. Encouraging education initiatives for pediatric primary care providers may encourage appropriate referral for AIS. PMID- 27412800 TI - Dihydropyridine calcium channel blockers and renal disease. AB - Although blood pressure control is considered the main mechanism for preventing the progression of chronic kidney disease (CKD), angiotensin-converting enzyme inhibitors and angiotensin receptors blockers have an additional organ-protective role. The effects of calcium channel blockers (CCBs) in renal disease are not so clearly defined. CCBs have pleiotropic effects that might contribute to protection of the kidney, such as attenuating the mesangial entrapment of macromolecules, countervailing the mitogenic effect of platelet-derived growth factors and platelet-activating factors and suppressing mesangial cell proliferation. Some evidence has accumulated in recent years demonstrating that the new dihydropyridinic CCBs (such as lercanidipine or efonidipine) may affect both postglomerular and preglomerular vessels, resulting in a decreased filtration fraction and nephroprotective effect. Increasing clinical and experimental evidence supports this view and the use of CCBs in CKD hypertensive patients. PMID- 27412804 TI - Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism. A propensity-matched cohort study. AB - Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency. PMID- 27412805 TI - Musculoskeletal infections associated with Citrobacter koseri. AB - Introduction Citrobacter koseri is a well known cause of central nervous system infections in the paediatric setting. Musculoskeletal infections caused by C koseri are rare, with only 14 previously reported cases. We present the first recorded case of C koseri induced septic arthritis of the knee along with a review of the literature. Methods A search of the PubMed, Embase((r)) and Google ScholarTM databases was undertaken. Only complete or near complete cases were reviewed. Findings Fourteen musculoskeletal infections were identified. Of these, five were associated with an operative procedure and five involved a septic joint. Surgical treatment was required in the majority of cases and cure was achieved in all cases following prolonged antibiotic use. Conclusions C koseri associated musculoskeletal infections may complicate primary orthopaedic procedures. The organism can present aggressively and can be difficult to identify microbiologically. It is sensitive to newer generation beta-lactams, cephalosporin-based antibiotics and timely surgery. PMID- 27412806 TI - Open intraperitoneal onlay mesh repair for medium-large lateral abdominal wall herniae. PMID- 27412807 TI - The use of intraoperative parathyroid hormone monitoring in minimally invasive parathyroid surgery. AB - Introduction Surgery is the first-line management option for patients with primary hyperparathyroidism (pHPT). Minimally invasive parathyroidectomy (MIP) is now preferable but few centres offer this service, mainly because of lack of intraoperative parathyroid hormone (IOPTH) testing. The aim of this study was to identify whether the measurement of IOPTH in patients having minimally invasive parathyroidectomy for pHPT alters their management. Methods A retrospective review was carried out of 78 consecutive patients who underwent parathyroid surgery by a single surgeon with a special interest in parathyroid surgery. The clinical impact of IOPTH monitoring was recorded postoperatively in a timely manner. Serum adjusted calcium levels were checked preoperatively (on admission) and one month postoperatively; normalisation was considered a cure. Results In the setting of curative MIP, IOPTH measurement did not influence the management in any of the patients but it could have led to bilateral parathyroid exploration (BPE) in three instances. Similarly, in cases that required lengthening of the MIP incision, IOPTH results did not influence patient management although it could have led to BPE in one case. Conclusion MIP offers an effective cure for patients with hyperparathyroidism. The addition of IOPTH testing adds increased expense, operating time and risk to patients otherwise suitable for MIP. PMID- 27412808 TI - Major abdominal surgery in Jehovah's Witnesses. AB - Introduction Patients who are Jehovah's Witnesses pose difficult ethical and moral dilemmas for surgeons because of their refusal to receive blood and blood products. This article outlines the personal experiences of six Jehovah's Witnesses who underwent major abdominal surgery at a single institution and also summarises the literature on the perioperative care of these patients. Methods The patients recorded their thoughts and the dilemmas they faced during their surgical journey. We also reviewed the recent literature on the ethical principles involved in treating such patients and strategies recommended to make surgery safer. Results All patients were supported in their decision making by the clinical team and the Hospital Liaison Committee for Jehovah's Witnesses. The patients recognised the ethical and moral difficulties experienced by clinicians in this setting. However, they described taking strength from their belief in Jehovah. A multitude of techniques are available to minimise the risk associated with major surgery in Jehovah's Witness patients, many of which have been adopted to minimise unnecessary use of blood products in general. Nevertheless, the risks of catastrophic haemorrhage and consequent mortality remain an unresolved issue for the treating team. Conclusions Respect for a patient's autonomy in this setting is the overriding ethical principle, with detailed discussion forming an important part of the preparation of a Jehovah's Witness for major abdominal surgery. Clinicians must be diligent in the documentation of the patient's wishes to ensure all members of the team can abide by these. PMID- 27412809 TI - Strangulated lumber hernias in adults: A case report and review of the literature. AB - Strangulated lumbar hernia is a very rare condition, with no more than 30 cases reported in the literature so far. Therefore, there is no specific management guideline and the diagnosis remains difficult. By reporting the case of a Senegalese male patient who had a preoperative diagnosis of strangulated lumbar hernia, we aim to discuss the diagnosis and therapeutic modalities of this rare entity, which is often misdiagnosed. PMID- 27412810 TI - The effect of micellization on the EPR spectra and reactivity of 2,2,4,4 tetramethylpiperidinoxyl (TEMPO) radicals. AB - A series of 4-alkanoyloxy-2,2,6,6-tetramethylpiperidinoxyl radicals was prepared, and their reactivity in water vis-a-vis antioxidant Trolox was compared. Spectral (electron paramagnetic resonance) and dynamic-light-scattering measurements suggested the formation of micelles for the more hydrophobic members of the series. The observed increase in reactivity for the micelle-forming radicals reflected the increased local concentration of the radical fragment on the micellar interface. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27412811 TI - Assessment of DNA-binding affinity of cholinesterase reactivators and electrophoretic determination of their effect on topoisomerase I and II activity. AB - In this paper, we describe the biochemical properties and biological activity of a series of cholinesterase reactivators (symmetrical bisquaternary xylene-linked compounds, K106-K114) with ctDNA. The interaction of the studied derivatives with ctDNA was investigated using UV-Vis, fluorescence, CD and LD spectrometry, and electrophoretic and viscometric methods. The binding constants K were estimated to be in the range 1.05 * 10(5)-5.14 * 10(6) M(-1) and the percentage of hypochromism was found to be 10.64-19.28% (from UV-Vis titration). The used methods indicate that the studied samples are groove binders. Electrophoretic methods proved that the studied compounds clearly influence calf thymus Topo I (at 5 MUM concentration, except for compounds K107, K111 and K114 which were effective at higher concentrations) and human Topo II (K110 partially inhibited Topo II effects even at 5 MUM concentration) activity. PMID- 27412812 TI - Modulation of chromatin function through linker histone H1 variants. AB - In this review, the structural aspects of linker H1 histones are presented as a background for characterization of the factors influencing their function in animal and human chromatin. The action of H1 histone variants is largely determined by dynamic alterations of their intrinsically disordered tail domains, posttranslational modifications and allelic diversification. The interdependent effects of these factors can establish dynamic histone H1 states that may affect the organization and function of chromatin regions. PMID- 27412813 TI - Edge phonons in black phosphorus. AB - Black phosphorus has recently emerged as a new layered crystal that, due to its peculiar and anisotropic crystalline and electronic band structures, may have important applications in electronics, optoelectronics and photonics. Despite the fact that the edges of layered crystals host a range of singular properties whose characterization and exploitation are of utmost importance for device development, the edges of black phosphorus remain poorly characterized. In this work, the atomic structure and behaviour of phonons near different black phosphorus edges are experimentally and theoretically studied using Raman spectroscopy and density functional theory calculations. Polarized Raman results show the appearance of new modes at the edges of the sample, and their spectra depend on the atomic structure of the edges (zigzag or armchair). Theoretical simulations confirm that the new modes are due to edge phonon states that are forbidden in the bulk, and originated from the lattice termination rearrangements. PMID- 27412814 TI - Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy. AB - Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) is a rapid diagnostic assay that can identify certain organisms growing in blood cultures 30 90 min from the time of positive Gram-stain. Existing studies have demonstrated a clinical utility with this assay when antibiotic stewardship programs assist clinicians with interpreting the results. However, the benefit of these rapid assays in the absence of concomitant antibiotic stewardship involvement is unclear. In this randomized study of 220 patients with enterococcal or streptococcal bacteremia, we found that PNA FISH, in the absence of concomitant input from an antibiotic stewardship program, had no impact on time to effective or optimal therapy, length of hospital stay, or in-hospital mortality. Our results suggest that in the absence of guidance from an antibiotic stewardship program, the clinical benefits of rapid diagnostic microbiological tools may be reduced. PMID- 27412815 TI - Insights into Borrelia miyamotoi infection from an untreated case demonstrating relapsing fever, monocytosis and a positive C6 Lyme serology. AB - We describe a patient from the United States with PCR- and serology-confirmed Borrelia miyamotoi infection who recovered without antibiotics. Our findings suggest that B. miyamotoi infection may cause relapsing fever, blood monocytosis and antibody reactivity to the C6 peptide. Further studies are required to better define the spectrum of clinical and laboratory findings for this emerging tick transmitted infection. PMID- 27412816 TI - Low concentration of ethanol favors progenitor cell differentiation and neovascularization in high-fat diet-fed mice model. AB - Endothelial progenitor cells (EPCs) and monocytic cells from bone marrow (BM) can be recruited to the injured endothelium and contribute to its regeneration. During metabolic diseases such as obesity and diabetes, progenitor cell function is impaired. Several studies have shown that moderate alcohol consumption prevents the development and progression of atherosclerosis in a variety of animal/mouse models and increases mobilization of progenitor cells. Along with these studies, we identify ethanol at low concentration as therapeutic tool to in vitro expand progenitor cells in order to obtain an adequate number of cells for their use in the treatment of cardiovascular diseases. We evaluated the effects of ethanol on the phenotype of BM-derived cells from mice fed with high-fat diet (HFD). HFD did not induce changes in weight of mice but induced metabolic alterations. HFD feeding increased the differentiation of monocytic progenitors but not EPCs. Whereas ethanol at 0.6% is able to increase monocytic progenitor differentiation, 1% ethanol diminished it. Furthermore, ethanol at 0.6% increased the ability of progenitor cells to promote in vivo angiogenesis as well as secretome of BM-derived cells from mice fed with HFD, but not in mice fed normal diet. In conclusion, ethanol at low concentration is able to increase angiogenic abilities of progenitor cells from animals with early metabolic alterations. PMID- 27412817 TI - Highly Selective Enrichment of Glycopeptides Based on Zwitterionically Functionalized Soluble Nanopolymers. AB - Efficient glycopeptides enrichment prior to mass spectrometry analysis is essential for glycoproteome study. ZIC-HILIC (zwitterionic hydrophilic interaction liquid chromatography) based glycopeptides enrichment approaches have been attracting more attention for several benefits like easy operating, high enrichment specificity and intact glycopeptide retained. In this study, Poly (amidoamine) dendrimer (PAMAM) was adopted for the synthesis of zwitterionically functionalized (ZICF) materials for glycopeptide enrichment. The multiple branched structure and good solubility of ZICF-PAMAM enables a sufficient interaction with glycopeptides. The ZICF-PAMAM combined with the FASP-mode enrichment strategy exhibits more superior performance compared with the existing methods. It has the minimum detectable concentration of femtomolar level and high recovery rate of over 90.01%, and can efficiently enrich glycopeptides from complex biological samples even for merely 0.1 MUL human serum. The remarkable glycopeptides enrichment capacity of ZICF-PAMAM highlights the potential application in in-depth glycoproteome research, which may open up new opportunities for the development of glycoproteomics. PMID- 27412819 TI - Comparison of biological chromophores: photophysical properties of cyanophenylalanine derivatives. AB - Within this work, the family of cyanophenylalanine spectroscopic reporters is extended by showing the ortho and meta derivatives have intrinsic photophysical properties that are useful for studies of protein structure and dynamics. The molar absorptivities of 2-cyanophenylalanine and 3-cyanophenylalanine are shown to be comparable to that of 4-cyanophenylalanine with similar spectral features in their absorbance and emission profiles, demonstrating that these probes can be utilized interchangeably. The fluorescence quantum yields are also on the same scale as commonly used fluorophores in peptides and proteins, tyrosine and tryptophan. These new cyano-fluorophores can be paired with either 4 cyanophenylalanine or tryptophan to capture distances in peptide structure through Forster resonance energy transfer. Additionally, the spectroscopic properties of these chromophores can report the local solvent environment via changes in fluorescence emission intensity as a result of hydrogen bonding and/or hydration. A decrease in the quantum yield is also observed in basic environments due to photoinduced electron transfer from a deprotonated amine in the free PheCN species and at the N-terminus of a short peptide, providing an avenue to detect pH in biological systems. Our results show the potential of these probes, 2 cyanophenylalanine and 3-cyanophenylalanine, to be incorporated into a single peptide chain, either individually or in tandem with 4-cyanophenylalanine, tryptophan, or tyrosine, in order to obtain information about peptide structure and dynamics. PMID- 27412818 TI - Association of Inter-arm Blood Pressure Difference with Asymptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients. AB - Inter-arm blood pressure (BP) difference has been associated with ischemic stroke. Local atherosclerosis of stroke differ among vulnerable individuals, whereas intracranial arterial stenosis (ICAS) is more frequently affected Asians, and extracranial arterial stenosis (ECAS) is more prevalent among whites. We hereby sought to explore the association of inter-arm BP difference with ICAS and ECAS in stroke-free hypertensive patients in Chinese population. All the 885 subjects were evaluated of ICAS and ECAS through computerized tomographic angiography. Both arm BP was measured simultaneously by Vascular Profiler-1000 device. In the continuous study, ICAS was significantly associated with age, male, average brachial SBP, diabetes, anti-hypertensive treatment and inter-arm DBP difference. ECAS was associated with age, inter-arm SBP and LDL. In the categorical study, subjects with the top quartile of inter-arm DBP difference (>=4 mmHg) showed significantly higher risk of ICAS (OR = 2.109; 95% CI, 1.24 3.587). And the participants with the top quartile of inter-arm SBP difference (>=6 mmHg) showed significantly higher risk of ECAS (OR = 2.288; 95% CI, 1.309 3.998). In conclusion, we reported a diverse association of inter-arm SBP/DBP difference with the ICAS/ECAS. Inter-arm DBP difference might be the early symbol of ICAS in Chinese population, which need further verification in long-term cohort study. PMID- 27412820 TI - Microbial Cells with a Fe3 O4 Doped Hydrogel Extracellular Matrix: Manipulation of Living Cells by Magnetic Stimulus. AB - This study aims to develop an effective method to control motile microorganisms and enable their manipulation as functional 'live micro/nano robots'. A novel strategy based on Fe3 O4 nanoparticle-doped alginate hydrogel is developed to fashion an artificial extracellular matrix (ECM) for microbial cells (e.g., Saccharomyces cerevisiae and Flavobacterium heparinum). During this strategy, a single layer of alginate hydrogel is coated around the microbial cells doped with Fe3 O4 nanoparticles to form the alg-mag-cells. Transmission electron microscopy shows that Fe3 O4 nanoparticles are uniformly distributed in the hydrogel shell. Together with maintaining the cell activity and metabolism, the hydrogel coated microbial cells demonstrate high magnetic responsiveness in an external magnetic field and are able to form micro-scaled patterns using the magnetic template designed in this study. This strategy provides a building block to fabricate advanced biological models, medical therapeutic products, and non-medical biological systems using different microorganisms. PMID- 27412822 TI - Liquid crystalline nanoparticles encapsulating cisplatin and docetaxel combination for targeted therapy of breast cancer. AB - Cancer remains a leading cause of death. A combination of anticancer agents can effectively kill cancer through multiple pathways; however, improvements to their delivery are needed. Hence, docetaxel and cisplatin-loaded liquid crystalline nanoparticles with folic acid were prepared for effective and targeted anticancer therapy. Notably, hydroxypropyl-beta-cyclodextrin/cisplatin complexes in 0.9% NaCl solution were used for the prevention of possible aquation of cisplatin, which would otherwise lead to severe adverse effects. The optimized nanoparticles exhibited small particle size, high drug loading capacity (>90%), and controlled drug release profiles. In vitro cell cytotoxicity assays demonstrated that the optimized nanoparticles were taken up by folate receptor-expressing cells to a greater extent than non-folate expressing cells, which is attributable to folate specific endocytosis of the optimized nanoparticles. Enhanced expression of apoptotic markers (Bax, p21, and cleaved caspase-3) along with enhanced anti migration effects in MDA-MB-231 cells following treatment suggests that the optimized nanoparticles provide an effective treatment for metastatic breast cancer. These results were further supported by in vivo findings obtained for a MDA-MB-231 tumor xenograft model. Altogether, the optimized nanoparticles may potentially be developed as an effective treatment modality for folate-targeted metastatic breast cancer treatment. PMID- 27412821 TI - The Synthetic Elicitor DPMP (2,4-dichloro-6-{(E)-[(3 methoxyphenyl)imino]methyl}phenol) Triggers Strong Immunity in Arabidopsis thaliana and Tomato. AB - Synthetic elicitors are drug-like compounds that are structurally distinct from natural defense elicitors. They can protect plants from diseases by activating host immune responses and can serve as tools for the dissection of the plant immune system as well as leads for the development of environmentally-safe pesticide alternatives. By high-throughput screening, we previously identified 114 synthetic elicitors that activate expression of the pathogen-responsive CaBP22(-333)::GUS reporter gene in Arabidopsis thaliana (Arabidopsis), 33 of which are [(phenylimino)methyl]phenol (PMP) derivatives or PMP-related compounds. Here we report on the characterization of one of these compounds, 2,4-dichloro-6 {(E)-[(3-methoxyphenyl)imino]methyl}phenol (DPMP). DPMP strongly triggers disease resistance of Arabidopsis against bacterial and oomycete pathogens. By mRNA-seq analysis we found transcriptional profiles triggered by DPMP to resemble typical defense-related responses. PMID- 27412824 TI - Alcohol-Induced C-N Bond Cleavage of Cyclometalated N-Heterocyclic Carbene Ligands with a Methylene-Linked Pendant Imidazolium Ring. AB - Reaction of the pentamethylcyclopentadienyl rhodium iodide dimer [Cp*RhI2 ]2 with 1,1'-diphenyl-3,3'-methylenediimidazolium diiodide in non-alcohol solvents, in the presence of base, led to the formation of bis-carbene complex [Cp*Rh(bis NHC)I]I (bis-NHC=1,1'-diphenyl-4,4'-methylenediimidazoline-5,5'-diylidene). In contrast, when employing alcohols as the solvent in the same reaction, cleavage of a methylene C-N bond is observed, affording ether-functionalized (cyclometalated) carbene ligands coordinated to the metal center and the concomitant formation of complexes with a coordinated imidazole ligand. Studies employing other 1,1'-diimidazolium salts indicate that the cyclometalation step is a prerequisite for the activation/scission of the C-N bond and, based on additional experimental data, a SN 2 mechanism for the reaction is tentatively proposed. PMID- 27412823 TI - Association of lifestyle and demographic factors with estrogenic and glucocorticogenic activity in Mexican American women. AB - Breast cancer risk is higher in US-born than in foreign-born Hispanics/Latinas and also increases with greater length of US residency. It is only partially known what factors contribute to these patterns of risk. To gain new insights, we tested the association between lifestyle and demographic variables and breast cancer status, with measures of estrogenic (E) and glucocorticogenic (G) activity in Mexican American women. We used Chemical-Activated LUciferase gene eXpression assays to measure E and G activity in total plasma from 90 Mexican American women, without a history of breast cancer at the time of recruitment, from the San Francisco Bay Area Breast Cancer Study. We tested associations of nativity, lifestyle and sociodemographic factors with E and G activity using linear regression models. We did not find a statistically significant difference in E or G activity by nativity. However, in multivariable models, E activity was associated with Indigenous American ancestry (19% decrease in E activity per 10% increase in ancestry, P = 0.014) and with length of US residency (28% increase in E activity for every 10 years, P = 0.035). G activity was associated with breast cancer status (women who have developed breast cancer since recruitment into the study had 21% lower G activity than those who have not, P = 0.054) and alcohol intake (drinkers had 25% higher G activity than non-drinkers, P = 0.015). These associations suggest that previously reported breast cancer risk factors such as genetic ancestry and alcohol intake might in part be associated with breast cancer risk through mechanisms linked to the endocrine system. PMID- 27412826 TI - Therapeutic Apheresis in Pregnancy: Three Differential Indications With Positive Maternal and Fetal Outcome. AB - Therapeutic apheresis (TA) is a complex extracorporeal procedure for the treatment of several acute and chronic diseases. TA in pregnancy is considered safe for both mother and fetus and has the same indications of non-pregnant patients. TA can be used during the entire course of the pregnancy with the following purposes: (i) to treat several maternal acute and chronic conditions; (ii) to treat fetal conditions; (iii) to avoid administration of drugs potentially harmful to the fetus; and (iv) to reach a more advanced gestational age in order to prevent fetal prematurity. We report three successfully treated patients throughout pregnancy, for differential indications: thrombotic thrombocytopenic purpura, red blood cells alloimmunization and ulcerative colitis. Multiple courses of TA have been performed without any complications for the mother and the fetus. A review and a discussion on the particular TA implications related to maternal-fetal medicine have been reported. When approaching TA in pregnancy, clinicians have to consider the severity of disease, the strength of the indications, and the gestational age. Each case must be evaluated individually on the basis of existing evidence since, despite the increasing use, specific guidelines for apheresis in pregnancy are still lacking. PMID- 27412825 TI - Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study. AB - Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk. PMID- 27412827 TI - Surprising Hofmeister Effects on the Bending Vibration of Water. AB - The Hofmeister series, which originally described the specific ion effects on the solubility of macromolecules in aqueous solutions, has been a long-standing unsolved and exceptionally challenging mystery in chemistry. The complexity of specific ion effects has prevented a unified theory from emerging. Accumulating research has suggested that the interactions among ions, water and various solutes play roles. However, among these interactions, the binding between ions and solutes is receiving most of the attention, whereas the effects of ions on the hydrogen-bond structure in liquid water have been deemed to be negligible. In this study, attenuated-total-reflectance Fourier transform infrared spectroscopy is used to study the infrared spectra of salt solutions. The results show that the red- and blue-shifts of the water bending band are in excellent agreement with the characteristic Hofmeister series, which suggests that the ions' effects on water structure might be the key role in the Hofmeister phenomenon. PMID- 27412828 TI - Blood pressure-lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies. AB - AIMS: It has been suggested that sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP lowering potential of sulodexide. METHODS: A post hoc analysis of the double blind, randomized, placebo-controlled sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and sulodexide on systolic BP (SBP) among albuminuria groups. RESULTS: Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g-1 , sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P < 0.001] compared with placebo, whereas a 2.3 mmHg (95% CI 0.9,3.7; P = 0.001) reduction was seen in subjects with a UACR of 300-1000 mg g-1 . Sulodexide did not lower SBP in subjects with a UACR <300 mg g-1 (-0.2 mmHg, 95% CI -0.8, 0.5; P = 0.60). SBP-lowering effects were not accompanied by changes in body weight. CONCLUSION: The BP-reducing potency of sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy. PMID- 27412829 TI - [Research and application: scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population]. AB - There is a large population at high risk for diabetes in China, and there has been a dramatic increase in the incidence of diabetes in the country over the past 30 years. Interventions targeting the individual risk factors of diabetes can effectively prevent diabetes; these include factors such as an unhealthy diet, lack of physical activity, overweight, and obesity, among others. Evaluation of related knowledge, attitudes, and behaviors before and after intervention using appropriate scales can measure population demands and the effectiveness of interventions. Scientificity and practicability are basic requirements of scale development. The theoretical basis and measuring items of a scale should be consistent with the theory of behavior change and should measure the content of interventions in a standardized and detailed manner to produce good validity, reliability, and acceptability. The scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population is a tool for demand evaluation and effect evaluation of lifestyle intervention that has good validity and reliability. Established by the National Center for Chronic and Noncommunicable Disease Control and Prevention, its use can help to decrease the Chinese population at high risk for diabetes through targeted and scientifically sound lifestyle interventions. Future development of intervention evaluation scales for useing in high-risk populations should consider new factors and characteristics of the different populations, to develop new scales and modify or simplify existing ones, as well as to extend the measurement dimensions to barriers and supporting environment for behaviors change. PMID- 27412830 TI - [The key problems in the population exposure assessment of hazardous chemicals accidents]. AB - Serious accidents of hazardous chemicals can cause a variety of acute or chronic impairment in human health. The effects of hazardous chemicals on human health can be identified by carrying on population exposure assessment. Through analyzing the domestic and overseas population exposure assessment cases related to hazardous chemicals accidents, we summarized that the base and key of the population exposure assessment were to identify the characteristics of the chemicals , delimit the area and the population exposed to the chemicals, and collect the data of the monitored chemicals and the population health in the polluted area. PMID- 27412831 TI - [Development of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population]. AB - OBJECTIVE: To establish a scale of knowledge, attitude, and behavior of lifestyle interventions among a population at high risk of diabetes with good cultural adaptability, validity, and reliability. METHODS: The original item pool was formed based on a literature review, group discussions, and interviews with experts. We used the Delphi method to determine core items of the scale (30 cases in the first round and 26 cases in the second round, respectively). We invited 30 experts from clinical medicine, nursing, preventive medicine, health education, and community diabetes prevention and control to completed expert consultation tables. For each item, experts were asked to provide an importance score, the judgment basis, and a familiarity score. We analyzed the positive coefficient, authoritative coefficient, degree of concentration, and harmonious coefficient, to determine the selected items. Using face-to-face questionnaire surveys, 31 participants at high risk of diabetes were selected for the pilot study. We analyzed understanding of the scale's content and presentation and corrected the scale based on the analysis. RESULTS: We received 26 and 23 inquiry forms, respectively, in two rounds of consultation. Responses rates of the two rounds were 87% and 88%. The scores of authoritative coefficients were 0.79 +/- 0.14 and 0.87 +/- 0.10. The score of total scale in the first consultation was 4.32+/ 0.25, the coefficient of variation was 0.06, and the coefficient of concordance was 0.163; in the second consultation, these were 4.58+/-0.21, 0.05, 0.150, respectively. In the first consultation, 22 experts proposed amendments and made suggestions, a rate of 85% (22/26). After the second round, 30 items were included in the final scale. In the pilot study, 13 males and 18 females with high risk of diabetes were interviewed. Average age of the population was (62.24 +/- 10.23) years. The time to complete the survey was (9.35 +/- 2.71) minutes. After the pilot study was completed, the order of the items was adjusted to ensure a reasonable and logical scale. CONCLUSION: We developed the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high risk population, using the Delphi method and a pilot study. Overall, the findings indicate that input from experts during development facilitates achievement of satisfactory concentration and coordination levels, and the use of this scale will produce credible results. PMID- 27412832 TI - [Validity, reliability, and acceptability of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population]. AB - OBJECTIVE: To evaluate the validity, reliability, and acceptability of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high risk population (HILKAB), and provide scientific evidence for its usage. METHODS: By convenient sampling, we selected 406 individuals at high risk for diabetes for survey using the HILKAB. Pearson correlation coefficient, factor analysis, independent sampling, and t-test for high- and low-score groups were used to evaluate the content validity, construct validity, and discriminant validity of the scale. Reliability of the scale was evaluated by internal consistency, which included Cronbach's alpha coefficient, theta coefficient, Omega coefficient, and split-half reliability. Scale acceptability was evaluated by acceptance rate and completion time of the survey. RESULTS: In this study, 366 questionnaires (90.1%) was qnalified and the completion time was (8.62+/-2.79) minutes. Scores for knowledge, attitude, and behavior were 10.60+/-3.73, 26.56+/-3.58, 17.09+/-9.74, respectively. The scale had good face validity and content validity. The correlation coefficient of items and the dimension to which they belong was between 0.25 and 0.97, and the correlation coefficient of three dimensions and the entire scale was between 0.64 and 0.91, all with P<0.001. Factor analysis of the scale extracted eight common factors. The cumulative variance contribution rate was 65.23%, thereby reaching the 50% approved standard. Of 30 items there were 29 items with factor loadings >=0.40, indicating the scale had good construct validity. For the high-score group, scores for knowledge, attitude, and behavior dimensions were 13.89+/-2.55, 29.56+/- 2.46, 28.05 +/- 2.93, respectively, which were higher than those for the low-score group (7.67 +/- 2.78, 23.89 +/- 3.35, 6.25 +/- 3.13); t-values were 55.14, 119.40, 95.29, respectively, with P<0.001. The scale consisted of three dimensions: knowledge, attitude, and behavior. The Cronbach's alpha coefficient was between 0.84 and 0.92, the theta coefficient was between 0.85 and 0.96, the Omega coefficient was between 0.90 and 0.94, and the split-half reliability was between 0.77 and 0.95, reaching the 0.70 standard letter. CONCLUSION: The validity, reliability, and acceptability of the HILKAB scale were satisfactory for use in a population at high risk of diabetes. PMID- 27412833 TI - [Validity, reliability, and acceptability of the brief version of the self management knowledge, attitude, and behavior assessment scale for diabetes patients]. AB - OBJECTIVE: To evaluate the validity, reliability, and acceptability of the brief version of the self-management knowledge, attitude, and behavior (KAB) assessment scale for diabetes patients. METHODS: Diabetes patients who were managed at the Xinkaipu Community Health Service Center of Tianxin in Changsha, Hunan Province were selected for survey by cluster sampling. A total of 350 diabetes patients were surveyed using the brief scale to collect data on knowledge, attitudes, and behaviors of self-management. Content validity was evaluated by Pearson correlation coefficient between the brief scale and subscales of knowledge, attitude, and behavior. Structure validity was evaluated by factor analysis, and discrimination validity was evaluated by an independent sample t-test between the high-score and low-score groups. Reliability was tested by internal consistency reliability and split-half reliability. The evaluation indexes of internal consistency reliability were Cronbach's alpha coefficients, theta coefficient, and Omega coefficient. Acceptability was evaluated by valid response rate and completion time of the brief scale. RESULTS: A total of 346(98.9%) valid questionnaires were returned, with average survey time of (11.43+/-3.4) minutes. Average score of the brief scale was 78.85 +/- 11.22; scores of the knowledge, attitude, and behavior subscales were 16.45 +/- 4.42, 21.33 +/- 2.03, and 41.07 +/- 8.34, respectively. Pearson correlation coefficients between the brief scale and the knowledge, attitude, and behavior subscales were 0.92, 0.42, and 0.60, respectively; P-values were all less than 0.01, indicating that the face validity and content validity of the brief scale were achieved to a good level. The common factor cumulative variance contribution rate of the brief scale and three subscales was from 53.66% to 61.75%, which achieved more than 50% of the approved standard. There were 11 common factors; 41 of the total 42 items had factor loadings above 0.40 in their relevant common factor, indicating that the brief scale and three subscales had good construct validity. Patients were divided into a high-score group and a low-score group, then scores of the brief scale and three subscales were compared between the groups using a t-test. The results were all significant, indicating that the brief scale and three subscales had good discriminate validity. Mean scores of the brief scale and three subscales of the high-score group were 91.55+/-6.81, 19.51+/-2.17, 22.74+/-1.88, and 49.30+/-6.20, respectively; these were higher than the low-score group (65.89+/-5.79, 12.29+/ 4.76, 20.22+/-1.88, and 33.39+/-6.17, respectively) with t-values 27.76, 13.31, 9.20, and 17.56 (P-values were less than 0.001). The Cronbach's alpha coefficient, theta coefficient, Omega coefficient, and split-half reliability of the brief scale were 0.83, 0.87, 0.96, and 0.84, respectively. These values for the three subscales were all above 0.70, except for the theta coefficient of the attitude subscale with 0.64, indicating that the brief scale and three subscales had acceptable internal consistency reliability. CONCLUSION: The brief version of the diabetes self-management knowledge, attitude, and behavior assessment scale showed good acceptability, validity, and reliability, to responsibly evaluate self-management KAB among patients with diabetes. PMID- 27412834 TI - [Follow-up study on the effects of lipid ratios on all-cause mortality among elderly adults in longevity areas of China]. AB - OBJECTIVE: To explore the association between lipid ratios and all-cause mortality among elderly adults aged 80 years and older living in longevity areas of China. METHODS: A total of 874 participants in the Chinese Longitudinal Healthy Longevity Survey during June 2009 were included in our baseline survey. Lipid concentrations were measured and lipid ratios including LDL-C/HDL-C, TG/HDL C, and atherosclerosis index (AI) were calculated at baseline, and the information on questionnaires, body measurement, and blood biochemical profiles was collected. Survival time and survival status were followed up in August 2012. Subjects were stratified into three groups (low, middle and high) by tertiles of lipid ratios. All-cause mortality was calculated. Cox regression models were used to assess the association of lipid ratios with mortality. RESULTS: During 38 months of follow-up, a total of 427 participants had died, 378 participants survived, and 69 participants were lost to follow-up; overall mortality was 50.5%. For these participants, P50 (P25-P75) values for LDL-C/HDL-C were 1.68 (1.22-2.05), 1.85 (1.34-2.16), and 1.78 (1.33-2.08), respectively (H=6.93, P=0.025); values for TG/HDL-C were 1.00 (0.79-1.34), 1.20 (0.97-1.53), and 1.23 (0.95-1.72), respectively (H=9.18, P=0.008). AIs were 2.12 (1.72-2.61), 2.27 (1.84-2.75), and 2.13 (1.80-2.58), respectively (H=6.37, P=0.041). Values for 38 month all-cause mortality were 53.1%, 50.0%, and 44.0% among participants with low, middle, and high LDL-C/HDL-C ratios (<1.39, 1.39-1.92, >=1.92), respectively (chi(2)=7.54, P=0.024); these values were 54.8%, 46.4%, and 45.3% among participants with low, middle, and high AIs (<1.83, 1.83-2.39, >=2.39), respectively (chi(2)=6.67, P=0.035). Each 1 unit increase of LDL-C/HDL-C, TG/HDL C , and AI corresponded to a 17%, 15%, and 13% decrease in 38-month all-cause mortality, respectively; adjusted HRs were 0.83 (0.72-0.97), 0.85 (0.74-0.99), and 0.87 (0.76-0.99), respectively. Compared with participants who had low LDL C/HDL-C ratios, high ratios were associated with lower risk of mortality (HR 0.88; (95% CI: 0.78-0.99)). Compared with low AIs, middle and high values were associated with lower risk of mortality HRs (95%CI) were 0.84 (0.72-0.98) and 0.87 (0.78-0.98);respectively. CONCLUSION: LDL-C/HDL-C, TG/HDL-C, and AI were negatively associated with all-cause mortality among elderly adults aged 80 years and older living in longevity areas of China. PMID- 27412835 TI - [Association between oxygen saturation and cognitive function in older adults from longevity areas in China]. AB - OBJECTIVE: To explore the relationship between oxygen saturation (SpO2) and cognitive function in older adults from longevity areas in China. METHODS: A total of 2 285 participants aged >=65 years according to the 2012 Chinese Longitudinal Healthy Longevity Survey were included in this study. Among them, 1 739 participants aged 65-99 years were randomly selected, and 546 participants aged >=100 years were totally involved. A standardized questionaire was used to collect the information of demographic characteristics, life styles, disease history, etc. Cognitive function was evaluated using the Mini Mental State Examination Scale. Arterial oxygen saturation and heart rate were measured by pulse oximetry. Differences in cognitive function between the low SpO2 group (<0.94) and normal SpO2 group (>=0.94) were analyzed, and logistic regression models were used to analyze the relationship between SpO2 and cognitive function. RESULTS: The total score of cognitive function was 22.6+/-9.7 for the 1 922 participants in the normal SpO2 group, and 18.8 +/- 11.0 for the 363 participants in the low SpO2 group (t=6.11, P<0.001). The proportion of cognitive impairment in the low SpO2 group was 36.6% (n=133), and 22.9% (n=441) in the normal SpO2 group (chi(2)=30.44, P<0.001). RESULTS from stepwise logistic regression analysis showed that the risk of cognitive impairment increased with each year of increased age (OR 1.07; (95% CI: 1.05-1.09), P<0.001). Low SpO2, vision disorders, impaired activities of daily living, dyslipidemia, unmarried status, and lack of exercise were also associated with increased risk of cognitive impairment (OR 1.64; (95% CI: 1.11-2.43), OR 1.73; (95% CI: 1.27-2.35), OR 3.54; (95% CI: 2.62-4.79), OR 1.38; (95% CI: 1.02-1.86), OR 2.05; (95% CI: 1.34-3.13), OR 1.83; (95% CI: 1.13-2.97), respectively, P<0.05). Stratified analysis by age group showed that the association between SpO2 and cognitive impairment was most significant in participants aged >=90 years (OR 1.58; (95% CI: 1.09-2.28), P=0.016). CONCLUSION: Low oxygen saturation was associated with higher risk of cognitive impairment in our population of elderly adults. PMID- 27412836 TI - [Association between the hypersensitive C-reactive protein and activities of daily living among elderly adults in longevity areas of China]. AB - OBJECTIVE: To explore the association between the hypersensitive C-reactive protein (hs-CRP) and activities of daily living (ADL) in elderly adults in longevity areas of China. METHODS: This analysis included data on 2 352 adults aged >=65 years from eight longevity areas from the Chinese Longitudinal Healthy Longevity Survey in 2012. We excluded information on adults who lacked ADL or blood test data; the final study population comprised 2 227 elderly adults. Using questionnaires, body measurement, and blood biochemical examination, information on demographic characteristics, lifestyle, ADL, blood pressure, blood lipids, and biomarkers was collected. Study participants who were able to independently carry out the six kinds of activities of daily living (bathing, dressing, indoor activities, toileting, eating, bowel and bladder control) comprised the normal ADL group, and those who could not were included in the impaired ADL group. A multivariate logistic regression model was used to analyze factors influencing ADL impairment. RESULTS: Among the 2 227 participants, 1 674 (75.2%) were included in the normal ADL group and 553 (24.8%) in the impaired ADL group. Among all participants. Adults in the normal ADL group had lower hs-CRP levels (P50 (P25-P75)=0.88; 0.38-2.29 mg/L) than those in the impaired ADL group (1.27; 0.47 4.28 mg/L); (Z=- 4.71, P<0.001). Participants in the normal ADL group also had lower hs-CRP elevation rates (214; 12.8%) than those in the impaired ADL group (125; 22.6%); (chi(2)= 31.06, P<0.001). Multivariate logistic regression analysis indicated that each age increase of one year increased the risk of ADL impairment by 1.08 times (OR 1.08 (95%CI: 1.07-1.10); P<0.001). Participants with increased hs-CRP levels, those of Han nationality, and participants with a previous history of stroke had a higher risk of ADL impairment (OR(95% CI) values were 1.42(1.04 1.94), 1.87(1.13-3.08), 2.81(1.87-4.23); P<0.05). Elderly adults who participated in recreational activities had a lower risk of impaired ADL (OR 0.29 (95%CI: 0.22 0.38); P<0.001). CONCLUSION: In this study among elderly adults living in longevity areas of China, hs-CRP levels were related to ADL and elevated hs-CRP was associated with a higher risk of ADL impairment. PMID- 27412837 TI - [Epidemic profile of mumps in China during 2004-2013]. AB - OBJECTIVE: To analyze the epidemiological characteristics of mumps in China from 2004 to 2013. METHODS: Data of mump cases occurring between 2004 and 2013 were gathered from the national notifiable disease reporting system in China (excluding Hong Kong, Macao, and Taiwan); only cases classified as "final card" , laboratory confirmed, or clinical diagnosis were included. Descriptive epidemiology techniques were used to analyze features of sex, age, trends over time, and geography. RESULTS: Average incidence of mumps between 2004 to 2013 was 24.20/100 000. Peaks were in 2011 and 2012, with incidence 33.9/100 000 (454 385/1.340 million) and 35.6/100 000 (479 518/1.347 million). Two seasonal peaks occurred regularly in years, one from April to July in the first year, and the other from November to January in the next year. During the study period, provinces with the highest incidence were Ningxia, Tibet, Xinjiang, and Guangxi; incidences were 72.1/100 000 (4 425/6.13 million), 48.5/100 000 (1 396/3 million), 51.7/100 000 (10 887/21.04 million), and 40.8/100 000 (19 179/46.99 million), respectively. Guangdong (28 078), Sichuan (21 924), Guangxi (21 616), and Zhejiang (20 000) provinces reported the highest number of mumps cases. Beijing, Tianjin, and Shanghai showed a consistently low incidence. Mumps cases occurred primarily among children aged 5-9 years, with incidence ranging from 118.2/100 000 to 281.4/100 000. In 2004-2008, the peak age was 6-8 years (174.1/100 000) and in 2009-2013, peak age was 5-7 years (234.5/100 000). CONCLUSION: The highest incidences of mumps in China were reported in 2011 and 2012, with children of school age constituting the majority of cases. PMID- 27412838 TI - [Spatial autocorrelation analysis of measles in China, 2005-2014]. AB - OBJECTIVE: To detect the spatial features of measles in China by means of spatial statistical analysis. METHODS: Data of prefecture-level measles cases and incidence from 2005 to 2014 were collected from the China Information System for Disease Control and Prevention. Information collected from the system included demographic characteristics, spatial distribution information, and diagnostic reports. Cases of unconfirmed measles and those with unknown address were ruled out. Cases from Hong Kong, Macao, Taiwan, and foreign countries were not included in this study. Maps were obtained from geographical boundary data at prefecture level from the Chinese Center for Disease Control and Prevention and demographic data from the National Bureau of Statistics. Based on different measures of measles elimination, we divided the data from 2005 to 2014 into three stages: stage 1 (2005-2008), stage 2 (2009-2012), and stage 3 (2013-2014). ArcGIS software was used to describe the spatial distribution and for global and local spatial autocorrelation analysis. RESULTS: The total number of confirmed measles cases reported in the system was 650 222, with average incidence 0.46/100 000. The highest reported incidence was in 2008 (9.95/100 000) and the lowest in 2012 (0.46/100 000). Average incidences for stages 1, 2, and 3 were 8.87/100 000, 1.99/100 000 and 2.96/100 000, respectively. Global Moran's I coefficients from 2005 to 2014 were 0.31, 0.08, 0.36, 0.56, 0.26, 0.48, 0.34, 0.20, 0.29 and 0.52, respectively; all were significant (P<0.05). Average incidences for high-high (H H) clusters in 2005-2008, 2009-2012, and 2013-2014 were 33.02/100 000, 7.06/100 000, 11.91/100 000, respectively. Western China had high-value clustering consistently throughout all three periods; however, the number of prefectures covered by high-value clusters and discrepancy in the incidence between western and eastern regions were low. Northeast and northern China had H-H clustering in stages 2 and 3. CONCLUSION: In this study, measles incidence was spatially autocorrelated at the prefecture level from 2005 to 2014. Although China has made great progress in the elimination of measles, H-H clusters were consistently present. A need remains in China for targeted measles prevention and control measures. PMID- 27412839 TI - [Mode of delivery among HIV-positive pregnant women in areas with high prevalence of HIV in China, 2007-2013]. AB - OBJECTIVE: To describe the changing demographic profile over time of pregnant women diagnosed with HIV infection, and trends in mode of delivery and pregnancy outcome. METHODS: An observational investigation was conducted based on a population of 1 128 HIV-positive pregnant women at eight sites in China in provinces with high prevalence of HIV among pregnant women and children between 2007 and 2013. The study area included Shangcai and Weishi counties in Henan province; Ruili and Longchuan counties and Linxiang prefecture in Yunnan province; Yining County in Xinjiang; and Lingshan county and Babu district in Guangxi province. Main outcome measures were maternal characteristics, mode of delivery, and related trends over time by Cochram-Mantel-Haenszel(CMH) chi(2) test. RESULTS: A total hospital delivery rate of 96.4% was reported. For each year during the period 2007-2013, hospital delivery rates were 95.1% (253/266), 94.8% (188/198), 93.7% (164/175), 98.8% (159/161), 98.6% (141/143), 97.4% (114/117), and 100.0% (68/68), respectively (chi(2)CMH=7.68, P=0.006). The neonatal survival rate increased by 0.7% incrementally from 2007 to 2013, with 98.5% (262/266), 99.0% (196/198), 99.4% (174/175), 99.4% (160/161), 100.0% (143/143), 100.0% (117/117), and 100.0% (68/68), respectively (chi(2)CMH=4.58, P=0.030). The proportions of vaginal deliveries in those years were 62.2% (166/266), 54.8% (109/198), 59.9% (105/175), 61.7% (100/161), 66.7% (96/143), 58.8% (69/117), and 66.7% (46/68), respectively (chi(2)CMH=1.19, P= 0.276). The average rate for midwives skilled in procedures such as artificial rupture of membranes and episiotomy was 37.8% (261/691), with proportions decreasing during the study period at 39.2% (65/166), 47.4% (52/109), 35.9% (38/105), 46.0% (46/100), 25.5% (25/96), 31.2% (22/69), and 28.3% (13/46), respectively (chi(2CMH)=6.76, P=0.009). CONCLUSION: The annual rate of reported hospital delivery increased between 2007 and 2013, with a declining rate of skilled midwifery over the same period. Survival of neonates born to HIV-infected mothers in China has increased to nearly equivalent levels as those of developed countries. PMID- 27412840 TI - [Analysis of microcephaly and related factors among 31 902 infants of Chongqing, China]. AB - OBJECTIVE: To analyze the status of head circumference development and related factors of microcephaly among infants in Chongqing, China. METHODS: We included infants aged 7-24 months who had received child health care services at a Chongqing hospital from 1 February 2010 to 1 November 2014. We collected data of sex, age, head circumference, childbirth conditions, mother's pregnancy history, infant feeding patterns, and parents' educational level. Ultimately, 31 902 infants (17 511 males and 14 391 females) were analyzed. The t-test was used to compare head circumference by sex, and logistic regression models used to analyze the related factors of microcephaly. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Among the different age groups (7-8, 9 10, 11-12, 13-18, and 19-24 months), head circumferences for males were (44.3+/ 1.3), (45.2+/-1.4), (46.1+/-1.5), (46.8+/-1.4), and (47.8+/-1.4) cm, respectively; for females, head circumferences were (43.1+/-1.3), (44.1+/-1.3), (44.8+/-1.4), (45.7+/-1.4), and (46.7+/-1.3)cm, respectively. Head circumference for males were all greater than those for girls (t-values were 32.09, 27.73, 32.21, 41.66, and 32.03, respectively; P<0.001). The rate of microcephaly was 3.2% (1 025/31 902) among infants. Birth weights and fetal times were related to microcephaly in infants, with OR (95% CI) values 0.15(0.13-0.18) and 1.31(1.11 1.54), respectively. Factors including urban location, delayed birth, cesarean section, formula feeding, and mixed feeding patterns might reduce the risks of microcephaly compared with suburban location, term birth, eutocia, and breastfeeding; OR (95% CI) values were 0.60 (0.52-0.68), 0.55 (0.44-0.70), 0.76 (0.67-0.87), 0.46 (0.32-0.67), and 0.51 (0.34-0.75), respectively. CONCLUSION: Head circumference development among infants in Chongqing was satisfactory. Family environmental factors, birth conditions, and feeding patterns were found to be important factors related to microcephaly. PMID- 27412841 TI - [Impact of liver cancer deaths on life expectancy in 14 counties (districts) from the Huai River Basin, 2013: relationship between the water environment and liver cancer]. AB - OBJECTIVE: To investigate the relationship between liver cancer and the water environment, we analyzed the life expectancy in 14 counties (districts), which form the Huai River Basin with respect to liver cancer deaths in 2013 and changes in the surface water quality from 2004 to 2010. METHODS: The study area included the 14 counties (districts) of the Huai River Basin in China. We obtained surveillance data for all causes of death in the study area during 2013, as well as data for International Classification of Diseases,Tenth Edition(ICD-10) code C22 or liver cancer. Life expectancy and life expectancy after elimination of liver cancer were then calculated. Based on water quality monitoring data from the China Environment Yearbook 2005-2011, we analyzed the water environment of the Huai River Basin, and changes in the water quality. According to the " Encyclopedia of Rivers and Lakes in China" (Huai River Basin section), we divided the river basin into five categories: upstream basin (upstream); midstream, north shore of the basin (midstream-north); midstream, south shore of the basin (midstream-south); downstream basin (downstream); and the Yishusi River Basin. To calculate the life expectancy and life expectancy after elimination of liver cancer in the study area, we used the Nemerow Pollution Index (NPI), to investigate the relationship between liver cancer and the water environment. RESULTS: Life expectancy in the 14 study districts varied from 68.99 years (Shenqiu County) to 78.85 years (Jinhu County). Gains in life expectancy after elimination of liver cancer varied from 0.86 to 0.31 years. Midstream-north showed the greatest improvement, with overall gain in life expectancy of 0.77 years; this gain was 1.04 years for males and 0.40 years for females. Yishusi River Basin showed the least improvement, with overall gain in life expectancy of 0.41 years; this gain was 0.54 years for males and 0.24 years for females. For the 7 years from 2004 to 2010, midstream-north had the highest annual NPI values, at 2.08, 1.74, 1.64, 1.81, 1.41, 1.26, and 1.06, respectively. There was a positive correlation between NPI and life expectancy gain for both males and females (r=0.64, P=0.014). There was positive correlation between NPI and life expectancy gain among males alone (r=0.64, P=0.014); there was no significant correlation between NPI and life expectancy gain among females (r=0.44, P=0.115). CONCLUSION: Liver cancer had a significant impact on life expectancy in the Huai River Basin. The gain in life expectancy was higher for males than for females. There is a possible relationship between liver cancer deaths and the water environment in the research area, but this study did not infer a causal association. PMID- 27412842 TI - [Acute impact of cold spells on mortality during 2001-2011 in Jiang'an district of Wuhan, China]. AB - OBJECTIVE: To evaluate the association between cold spells and nonaccidental mortality from 2001 to 2011 in the Jiang'an District of Wuhan, China. METHODS: We collected mortality data for December 2001 to 2010 and January to March 2002 to 2011 in the study area. According to the International Classification of Diseases, we stratified the mortality data into three cause-specific categories: nonaccidental mortality, cardiovascular mortality, and respiratory mortality. We also obtained meteorological data (from the China Meteorological Administration) and ambient pollution data (from the Wuhan Environmental Monitoring Center) during the same periods. In the present study, a cold spell was defined as 5 or more consecutive days with daily average temperatures below the 5th percentile of daily mean temperatures (2.58 C) from January to December in 2001-2011. A distributed lag nonlinear model (DLNM) was applied to assess the acute effect of cold spells on daily nonaccidental mortality. RESULTS: During the study period, the total number of nonaccidental deaths was 17 119, including 9 403 (75.5%) among individuals aged over 65 years; 7 968 (46.5%) people died of cardiovascular disease. According to this definition, there were a total of 13 cold spell events and 111 days of duration in Wuhan during the study period. Study days were divided into three periods: non-cold spell days, 2008 cold spell days, and cold spell days in other years. Average daily mean temperatures of the above three periods were (8.2+/-4.5), (-0.7+/-1.4), and (0.8+/-1.2) C, respectively, corresponding to average daily deaths of 14.0+/-4.2, 18.2+/-4.5, and 14.9+/-4.9 for nonaccidental mortality. After adjusting for long-term trends, seasonal trends, weekdays, holidays, and relative humidity, analysis by the DLNM revealed that cold spells were associated with increased mortality risk, with a cumulative relative risk (RR) of 1.56 (95% CI: 1.36-1.79) at lag 0-27 days in 2008, higher than that in other years with 1.23 (95%CI: 1.08-1.41). Cold spells were not significantly associated with respiratory mortality and people under 65 years of age; however, during the 2008 cold spell RR increased to 1.96 (95% CI: 1.62-2.37) and 1.67 (95% CI: 1.43-1.95) for cardiovascular mortality and older adults (>=65 years old), respectively; both males and females had high mortality risk, with RRs of 1.60 (95%CI:1.33-1.92) and 1.50 (95% CI: 1.23-1.84), respectively. The association between cold spells and mortality remained nearly unchanged with and without adjustment for ambient pollutants (PM10, SO2, and NO2) in the DLNMs. CONCLUSION: In Wuhan, both the 2008 cold spell and cold spells in other years were significantly associated with increased nonaccidental mortality. People with cardiovascular disease and elderly adults may be more susceptible to the impact of cold spells on mortality. PMID- 27412843 TI - [Effectiveness of bupropion and counseling for smoking cessation]. AB - OBJECTIVE: To evaluate the effectiveness of bupropion for smoking cessation among Chinese smokers at a smoking cessation clinic. METHODS: A prospective observational study was conducted in a hospital located in Beijing during 2008 and from 28 to 31 October 2014. A total of 287 smokers (265 men and 22 women) were assessed using data from structured questionnaires at baseline and were followed up at 1 and 6 months. Trained physician counselors provided free brief education and individual counseling sessions for all participants at the first visit. A total 131 participants were prescribed bupropion in addition to counseling. The counseling plus bupropion group was compared with the group who underwent counseling without bupropion. Outcomes were self-reported 7-day point prevalence abstinence rates at 1- and 6-month follow-up and continuous abstinence rates at 6-month follow-up. Smoking reduction rates at 1 and 6 months were also measured. RESULTS: By intention-to-treat analysis, the 7-day point prevalence abstinence rate of the bupropion group at 1 and 6 months was higher than for the counseling-only group: at 1-month follow-up, 26.0% (34/131) vs. 15.4% (24/156), with OR (95% CI) 1.93(1.07-3.46); these rates at 6-month follow-up were 27.8% (35/131) vs. 15.4% (24/156), with OR (95% CI) 2.01(1.12-3.59). The 1-month continuous abstinence rate at 6 months was higher in the bupropion group: 26.0% (34/131) vs. 14.7% (23/156), with OR (95%CI) 2.03(1.12-3.66). Participants in the bupropion group also had a higher smoking reduction rate at 1 month than those in the counseling-only group: 55.0% (72/131) vs. 38.5% (60/156), with OR (95%CI) 1.95 (1.22-3.13). CONCLUSION: Prescription of bupropion at this smoking cessation clinic was effective in doubling the quitting rates and smoking reduction rates among Chinese smokers. PMID- 27412844 TI - [Comparison of embryotoxicity of di(2-ethylhexyl) phthalate using mouse and human embryonic stem cell test models in vitro]. AB - OBJECTIVE: To establish a mouse embryonic stem cell test (mEST) model and human embryonic stem cell test (hEST) model, to evaluate the embryotoxicity of di(2 ethylhexyl) phthalate (DEHP). METHODS: We developed mEST and hEST models according to the European Centre for the Validation of Alternative METHODS (ECVAM). We used penicillin G (PN-G) as the standard negative reference and 5 fluorouracil (5-FU) as the standard positive reference, respectively, to verify validity of the models. Based on model validity, mouse embryonic stem cells D3 (mESC-D3), mouse Balb/c-3T3 (3T3), and human embryonic stem cells H9 (hESC-H9) were administered different concentrations of DEHP (15.6, 31.2, 62.5, 125.0, 250.0, 500.0, and 1 000.0 MUg/ml) for 7 days. A cell counting Kit-8 was used to detect the 50% inhibitory proliferation concentration (IC50) of mESC-D3 cells, 3T3 cells, and hESC-H9 with DEHP. mESC-D3 and hESC-H9 were treated with DEHP (15.6, 31.2, 62.5, 125.0, 250.0 MUg/ml, and 500.0 MUg/ml) for 10 days based on the cytotoxicity results. At day 10, the expression of cardiomyocyte differentiation gene alpha-myosin heavy chain (alpha-MHC) was detected by real time PCR and the 50% inhibition of cardiomyocycte differentiation (ID50) determined. Based on the values of IC50 and ID50, functions I, II and II could be calculated by three linear discriminant functions in the EST model and the embryotoxicity of DEHP described by comparing the three functions. RESULTS: Nontrophoblast lineage both ES cells were cultured under optimal conditions and highly expressed hESC markers OCT4 , SSEA4, and TRA-1-60. The embryoid bodies formed were uniform in size and shape, and these results were highly repeatable. The PN-G and 5-FU results coincided with the prediction by ECVAM. Validation of our EST models was satisfactory. RESULTS of the three endpoints of DEHP in mEST were 197.3 MUg/ml (IC50 3T3), 210.0 MUg/ml (IC50 D3) and 246.8 MUg/ml (ID50 D3). DEHP was evaluated to be a nonembryotoxic compound based on values of function I (7.78), function II (7.58) and function III (-7.79). The three endpoints of DEHP in hEST were 195.4 MUg/ml (IC50 3T3), 184.8 ug/ml (IC50 D3), and 84.3 ug/ml (ID50). By comparing the values of function I (3.21), function II (5.77), and function III (-6.46), DEHP was evaluated to be weakly embryotoxic. CONCLUSION: DEHP was determined to be a nonembryotoxic compound by mEST and weakly embryotoxic by hEST. Therefore, hEST is a more sensible model for the evaluation of DEHP embryotoxicity. PMID- 27412845 TI - [Investigation on the tobacco epidemic and smoking attitudes among residents at early tobacco control legislation in Qingdao city]. PMID- 27412847 TI - [An epidemiologic study of familial aggregation of pertussis]. PMID- 27412846 TI - [Trend in incidence of thyroid cancer in Jiading district of Shanghai, 2003 2013]. PMID- 27412849 TI - Role of donor-acceptor macrocycles in sequence specific peptide recognition and their optoelectronic properties: a detailed computational insight. AB - In this study, we have considered an experimentally synthesized organic donor acceptor (D-A) macrocycle (CPP-TCAQ) and have modified it by incorporating different acceptor groups. We have performed density functional theory and classical molecular dynamics studies on these D-A macrocycles. We have clearly shown that cyclo[10]paraphenylene-2,6-tetracyanoanthraquinodimethanylene (CPP TCAQ) isomers interact specifically with one particular peptide sequence tyr-leu ala, over its structural isomer, tyr-ala-leu. However, other functionalized macrocycles bind to the tyr-ala-leu peptide sequence over tyr-leu-ala. Our calculations show that the presence of hydrogen bonds as well as pi-pi interactions responsible for this specific selection. Interestingly, it is the additional charge transfer induced dipolar interactions that favour binding of the tripeptide with the bulky C-terminal leucine amino acid, tyr-ala-leu. We confirmed that these host-guest complexes are stable in water medium as well as at room temperature. Thus, these hosts can bind effectively to any protein fragment bearing a particular tripeptide. Interestingly, the macrocycle, which recognizes the peptide sequence with a bulky C-terminal amino acid, also shows photophysical properties. The reasons for this happen to be the same (dipolar interactions introduce dipole allowed states for optical absorption as well as attracting the oppositely oriented dipolar groups). Recognition of the peptide sequence with a bulky C-terminal group is carried out for the first time with this functionalised macrocycle, which in addition shows photophysical properties. PMID- 27412850 TI - In vitro metabolism of the anti-inflammatory clerodane diterpenoid polyandric acid A and its hydrolysis product by human liver microsomes and recombinant cytochrome P450 and UDP-glucuronosyltransferase enzymes. AB - 1. The metabolism of the anti-inflammatory diterpenoid polyandric acid A (PAA), a constituent of the Australian Aboriginal medicinal plant Dodonaea polyandra, and its de-esterified alcohol metabolite, hydrolysed polyandric acid A (PAAH) was studied in vitro using human liver microsomes (HLM) and recombinant UDP glucuronosyltransferase (UGT) and cytochrome P450 (CYP) enzymes. 2. Hydrolysis of PAA to yield PAAH occurred upon incubation with HLM. Further incubations of PAAH with HLM in the presence of UGT and CYP cofactors resulted in significant depletion, with UGT-mediated depletion as the major pathway. 3. Reaction phenotyping utilising selective enzyme inhibitors and recombinant human UGT and CYP enzymes revealed UGT2B7 and UGT1A1, and CYP2C9 and CYP3A4 as the major enzymes involved in the metabolism of PAAH. 4. Analysis of incubations of PAAH with UDP-glucuronic acid-supplemented HLM and recombinant enzymes by UPLC/MS/MS identified three glucuronide metabolites. The metabolites were further characterised by beta-glucuronidase and mild alkaline hydrolysis. The acyl glucuronide of PAAH was shown to be the major metabolite. 5. This study demonstrates the in vitro metabolism of PAA and PAAH and represents the first systematic study of the metabolism of an active constituent of an Australian Aboriginal medicinal plant. PMID- 27412848 TI - New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections. AB - Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 MUM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites. PMID- 27412851 TI - Effects of realgar on GSH synthesis in the mouse hippocampus: Involvement of system XAG(-), system XC(-), MRP-1 and Nrf2. AB - Realgar is a type of mineral drug that contains arsenic and has neurotoxicity. Glutathione (GSH), which is the main antioxidant in the central nervous system, plays a key role in antioxidant defenses and the detoxification of arsenic. However, whether realgar interferes with the synthesis of GSH in the brain and the molecular mechanisms underlying its effects are largely unknown. Here, we used mouse models of exposure to realgar to show that realgar affects the synthesis of GSH in the hippocampus, leading to ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive abilities, and that the mechanisms that cause this effect may be associated with alterations in the expression of system XAG(-), system XC(-), multidrug resistance-associated protein 1(MRP-1), nuclear factor E2-related factor 2 (Nrf2), gamma glutamylcysteine synthetase (gamma-GCS), and the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid. These findings provide a theoretical basis for preventing the drug-induced chronic arsenic poisoning in the nervous system that is triggered by realgar. PMID- 27412853 TI - The ethics of conducting molecular autopsies in cases of sudden death in the young. PMID- 27412856 TI - Structures and electrical properties of single nanoparticle junctions assembled using LaC2-encapsulating carbon nanocapsules. AB - As the miniaturization of integrated circuits advances, electronics using single molecules and nanosize particles are being studied increasingly. Single nanoparticle junctions (SNPJs) consist of two electrodes sandwiching a single nanoparticle. Nanocarbons with nanospaces in their center, such as fullerenes, carbon nanotubes, and carbon nanocapsules (CNCs), are expected to be elements of advanced SNPJs. In this study, SNPJs were assembled using lanthanum dicarbide (LaC2)-encapsulating CNCs and two gold (Au) electrodes by a nanotip operation inside a high-resolution transmission electron microscope. The atomic configuration and electrical resistance of the SNPJs were investigated in situ. The results implied that the electrical resistance of the SNPJ depended on the interface structures of the contacts between the CNC and Au electrodes, i.e., the contact electrical resistance, and the greatest portion of the current through the SNPJ flowed along the outermost carbon layer of the CNC. Thus, the resistance of the SNPJs using the CNCs was demonstrated and the electrical conduction mechanism of one of the CNC was discussed in this study. PMID- 27412854 TI - Direct estimate of the rate of germline mutation in a bird. AB - The fidelity of DNA replication together with repair mechanisms ensure that the genetic material is properly copied from one generation to another. However, on extremely rare occasions when damages to DNA or replication errors are not repaired, germline mutations can be transmitted to the next generation. Because of the rarity of these events, studying the rate at which new mutations arise across organisms has been a great challenge, especially in multicellular nonmodel organisms with large genomes. We sequenced the genomes of 11 birds from a three generation pedigree of the collared flycatcher (Ficedula albicollis) and used highly stringent bioinformatic criteria for mutation detection and used several procedures to validate mutations, including following the stable inheritance of new mutations to subsequent generations. We identified 55 de novo mutations with a 10-fold enrichment of mutations at CpG sites and with only a modest male mutation bias. The estimated rate of mutation per site per generation was 4.6 * 10(-9), which corresponds to 2.3 * 10(-9) mutations per site per year. Compared to mammals, this is similar to mouse but about half of that reported for humans, which may be due to the higher frequency of male mutations in humans. We confirm that mutation rate scales positively with genome size and that there is a strong negative relationship between mutation rate and effective population size, in line with the drift-barrier hypothesis. Our study illustrates that it should be feasible to obtain direct estimates of the rate of mutation in essentially any organism from which family material can be obtained. PMID- 27412857 TI - Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol. AB - Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p < .05), whereas the CDD patients performed poorly in all the assessed memory types (p < .05). In addition, the CID patients had higher levels (mean difference [95% CI]) of corticotrophin-releasing hormone, cortisol (31.98 [23.97, 39.98] MUg/l), total triiodothyronine (667.58 [505.71, 829.45] MUg/l), and total thyroxine (41.49 [33.23, 49.74] MUg/l) (p < .05), and lower levels of thyrotropin-releasing hormone (-35.93 [-38.83, -33.02] ng/l), gonadotropin-releasing hormone (-4.50 [-5.02, -3.98] ng/l) (p < .05), and adrenocorticotropic hormone compared to the CDD patients. After controlling for confounding variables, the partial correlation analysis revealed that the levels of cortisol positively correlated with the errors in object working memory (r = .534, p = .033) and negatively correlated with the errors in object recognition memory (r = -.659, p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels. PMID- 27412858 TI - Protein-protein docking by fast generalized Fourier transforms on 5D rotational manifolds. AB - Energy evaluation using fast Fourier transforms (FFTs) enables sampling billions of putative complex structures and hence revolutionized rigid protein-protein docking. However, in current methods, efficient acceleration is achieved only in either the translational or the rotational subspace. Developing an efficient and accurate docking method that expands FFT-based sampling to five rotational coordinates is an extensively studied but still unsolved problem. The algorithm presented here retains the accuracy of earlier methods but yields at least 10 fold speedup. The improvement is due to two innovations. First, the search space is treated as the product manifold [Formula: see text], where [Formula: see text] is the rotation group representing the space of the rotating ligand, and [Formula: see text] is the space spanned by the two Euler angles that define the orientation of the vector from the center of the fixed receptor toward the center of the ligand. This representation enables the use of efficient FFT methods developed for [Formula: see text] Second, we select the centers of highly populated clusters of docked structures, rather than the lowest energy conformations, as predictions of the complex, and hence there is no need for very high accuracy in energy evaluation. Therefore, it is sufficient to use a limited number of spherical basis functions in the Fourier space, which increases the efficiency of sampling while retaining the accuracy of docking results. A major advantage of the method is that, in contrast to classical approaches, increasing the number of correlation function terms is computationally inexpensive, which enables using complex energy functions for scoring. PMID- 27412859 TI - Endogenous N-acyl taurines regulate skin wound healing. AB - The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two long-chain saturated NATs-N-tetracosanoyl-taurine [NAT(24:0)] and N eicosanoyl-taurine [NAT(20:0)]-as primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair-associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of wound-healing control in mammalian skin, which might be targeted for chronic wound therapy. PMID- 27412860 TI - Evolutionary alteration of ALOX15 specificity optimizes the biosynthesis of antiinflammatory and proresolving lipoxins. AB - ALOX15 (12/15-lipoxygenase) orthologs have been implicated in maturational degradation of intracellular organelles and in the biosynthesis of antiinflammatory and proresolving eicosanoids. Here we hypothesized that lower mammals (mice, rats, pigs) express 12-lipoxygenating ALOX15 orthologs. In contrast, 15-lipoxygenating isoforms are found in higher primates (orangutans, men), and these results suggest an evolution of ALOX15 specificity. To test this hypothesis we first cloned and characterized ALOX15 orthologs of selected Catarrhini representing different stages of late primate evolution and found that higher primates (men, chimpanzees) express 15-lipoxygenating orthologs. In contrast, lower primates (baboons, rhesus monkeys) express 12-lipoxygenating enzymes. Gibbons, which are flanked in evolution by rhesus monkeys (12 lipoxygenating ALOX15) and orangutans (15-lipoxygenating ALOX15), express an ALOX15 ortholog with pronounced dual specificity. To explore the driving force for this evolutionary alterations, we quantified the lipoxin synthase activity of 12-lipoxygenating (rhesus monkey, mouse, rat, pig, humIle418Ala) and 15 lipoxygenating (man, chimpanzee, orangutan, rabbit, ratLeu353Phe) ALOX15 variants and found that, when normalized to their arachidonic acid oxygenase activities, the lipoxin synthase activities of 15-lipoxygenating ALOX15 variants were more than fivefold higher (P < 0.01) [corrected]. Comparative molecular dynamics simulations and quantum mechanics/molecular mechanics calculations indicated that, for the 15-lipoxygenating rabbit ALOX15, the energy barrier for C13 hydrogen abstraction (15-lipoxygenation) was 17 kJ/mol lower than for arachidonic acid 12-lipoxygenation. In contrast, for the 12-lipoxygenating Ile418Ala mutant, the energy barrier for 15-lipoxygenation was 10 kJ/mol higher than for 12 lipoxygenation. Taken together, our data suggest an evolution of ALOX15 specificity, which is aimed at optimizing the biosynthetic capacity for antiinflammatory and proresolving lipoxins. PMID- 27412861 TI - A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases. AB - Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply. PMID- 27412862 TI - Robust high-performance nanoliter-volume single-cell multiple displacement amplification on planar substrates. AB - The genomes of large numbers of single cells must be sequenced to further understanding of the biological significance of genomic heterogeneity in complex systems. Whole genome amplification (WGA) of single cells is generally the first step in such studies, but is prone to nonuniformity that can compromise genomic measurement accuracy. Despite recent advances, robust performance in high throughput single-cell WGA remains elusive. Here, we introduce droplet multiple displacement amplification (MDA), a method that uses commercially available liquid dispensing to perform high-throughput single-cell MDA in nanoliter volumes. The performance of droplet MDA is characterized using a large dataset of 129 normal diploid cells, and is shown to exceed previously reported single-cell WGA methods in amplification uniformity, genome coverage, and/or robustness. We achieve up to 80% coverage of a single-cell genome at 5* sequencing depth, and demonstrate excellent single-nucleotide variant (SNV) detection using targeted sequencing of droplet MDA product to achieve a median allelic dropout of 15%, and using whole genome sequencing to achieve false and true positive rates of 9.66 * 10(-6) and 68.8%, respectively, in a G1-phase cell. We further show that droplet MDA allows for the detection of copy number variants (CNVs) as small as 30 kb in single cells of an ovarian cancer cell line and as small as 9 Mb in two high grade serous ovarian cancer samples using only 0.02* depth. Droplet MDA provides an accessible and scalable method for performing robust and accurate CNV and SNV measurements on large numbers of single cells. PMID- 27412863 TI - Thermodynamic control of anvil cloud amount. AB - General circulation models show that as the surface temperature increases, the convective anvil clouds shrink. By analyzing radiative-convective equilibrium simulations, we show that this behavior is rooted in basic energetic and thermodynamic properties of the atmosphere: As the climate warms, the clouds rise and remain at nearly the same temperature, but find themselves in a more stable atmosphere; this enhanced stability reduces the convective outflow in the upper troposphere and decreases the anvil cloud fraction. By warming the troposphere and increasing the upper-tropospheric stability, the clustering of deep convection also reduces the convective outflow and the anvil cloud fraction. When clouds are radiatively active, this robust coupling between temperature, high clouds, and circulation exerts a positive feedback on convective aggregation and favors the maintenance of strongly aggregated atmospheric states at high temperatures. This stability iris mechanism likely contributes to the narrowing of rainy areas as the climate warms. Whether or not it influences climate sensitivity requires further investigation. PMID- 27412865 TI - Charge transport through dicarboxylic-acid-terminated alkanes bound to graphene gold nanogap electrodes. AB - Graphene-based electrodes are attractive for single-molecule electronics due to their high stability and conductivity and reduced screening compared with metals. In this paper, we use the STM-based matrix isolation I(s) method to measure the performance of graphene in single-molecule junctions with one graphene electrode and one gold electrode. By measuring the length dependence of the electrical conductance of dicarboxylic-acid-terminated alkanes, we find that the transport is consistent with phase-coherent tunneling, but with an attenuation factor of betaN = 0.69 per methyl unit, which is lower than the value measured for Au molecule-Au junctions. Comparison with density-functional-theory calculations of electron transport through graphene-molecule-Au junctions and Au-molecule-Au junctions reveals that this difference is due to the difference in Fermi energies of the two types of junction, relative to the frontier orbitals of the molecules. For most molecules, their electrical conductance in graphene-molecule-Au junctions is higher than that in Au-molecule-Au junctions, which suggests that graphene offers superior electrode performance, when utilizing carboxylic acid anchor groups. PMID- 27412864 TI - Vancomycin gene selection in the microbiome of urban Rattus norvegicus from hospital environment. AB - BACKGROUND AND OBJECTIVES: Widespread use of antibiotics has resulted in selection pressure on genes that make bacteria non-responsive to antibiotics. These antibiotic-resistant bacteria are currently a major threat to global health. There are various possibilities for the transfer of antibiotic resistance genes. It has been argued that animal vectors such as Rattus norvegicus (R. norvegicus) living in hospital sewage systems are ideal for carrying pathogens responsible for fatal diseases in humans. METHODOLOGY: Using a metagenomic sequencing approach, we investigated faecal samples of R. norvegicus from three major cities for the presence of antibiotic resistance genes. RESULTS: We show that despite the shared resistome within samples from the same geographic locations, samples from hospital area carry significantly abundant vancomycin resistance genes. CONCLUSIONS AND IMPLICATIONS: The observed pattern is consistent with a selection for vancomycin genes in the R. norvegicus microbiome, potentially driven by the outflow of antibiotics and antibiotic-resistant bacteria into the wastewater systems. Carriage of vancomycin resistance may suggest that R. norvegicus is acting as a reservoir for possible transmission to the human population. PMID- 27412867 TI - Impact of Routine Fractional Flow Reserve Evaluation During Coronary Angiography on Management Strategy and Clinical Outcome: One-Year Results of the POST-IT. AB - BACKGROUND: Penetration of fractional flow reserve (FFR) in clinical practice varies extensively, and the applicability of results from randomized trials is understudied. We describe the extent to which the information gained from routine FFR affects patient management strategy and clinical outcome. METHODS AND RESULTS: Nonselected patients undergoing coronary angiography, in which at least 1 lesion was interrogated by FFR, were prospectively enrolled in a multicenter registry. FFR-driven change in management strategy (medical therapy, revascularization, or additional stress imaging) was assessed per-lesion and per patient, and the agreement between final and initial strategies was recorded. Cardiovascular death, myocardial infarction, or unplanned revascularization (MACE) at 1 year was recorded. A total of 1293 lesions were evaluated in 918 patients (mean FFR, 0.81+/-0.1). Management plan changed in 406 patients (44.2%) and 584 lesions (45.2%). One-year MACE was 6.9%; patients in whom all lesions were deferred had a lower MACE rate (5.3%) than those with at least 1 lesion revascularized (7.3%) or left untreated despite FFR<=0.80 (13.6%; log-rank P=0.014). At the lesion level, deferral of those with an FFR<=0.80 was associated with a 3.1-fold increase in the hazard of cardiovascular death/myocardial infarction/target lesion revascularization (P=0.012). Independent predictors of target lesion revascularization in the deferred lesions were proximal location of the lesion, B2/C type and FFR. CONCLUSIONS: Routine FFR assessment of coronary lesions safely changes management strategy in almost half of the cases. Also, it accurately identifies patients and lesions with a low likelihood of events, in which revascularization can be safely deferred, as opposed to those at high risk when ischemic lesions are left untreated, thus confirming results from randomized trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835808. PMID- 27412866 TI - Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease. AB - Neuropsychiatric symptoms (NPSs) often occur in early-age-of-onset Alzheimer's disease (EOAD) and cluster into sub-syndromes (SSy). The aim of this study was to investigate the association between 18 F-FDG-PET regional and connectivity-based brain metabolic dysfunctions and neuropsychiatric SSy. NPSs were assessed in 27 EOAD using the Neuropsychiatric Inventory and further clustered into four SSy (apathetic, hyperactivity, affective, and psychotic SSy). Eighty-five percent of EOAD showed at least one NPS. Voxel-wise correlations between SSy scores and brain glucose metabolism (assessed with 18 F-FDG positron emission tomography) were studied. Interregional correlation analysis was used to explore metabolic connectivity in the salience (aSN) and default mode networks (DMN) in a larger sample of EOAD (N = 51) and Healthy Controls (N = 57). The apathetic, hyperactivity, and affective SSy were highly prevalent (>60%) as compared to the psychotic SSy (33%). The hyperactivity SSy scores were associated with increase of glucose metabolism in frontal and limbic structures, implicated in behavioral control. A comparable positive correlation with part of the same network was found for the affective SSy scores. On the other hand, the apathetic SSy scores were negatively correlated with metabolism in the bilateral orbitofrontal and dorsolateral frontal cortex known to be involved in motivation and decision making processes. Consistent with these SSy regional correlations with brain metabolic dysfunction, the connectivity analysis showed increases in the aSN and decreases in the DMN. Behavioral abnormalities in EOAD are associated with specific dysfunctional changes in brain metabolic activity, in particular in the aSN that seems to play a crucial role in NPSs in EOAD. Hum Brain Mapp 37:4234 4247, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27412868 TI - Everolimus-Eluting Stents in Patients With Bare-Metal and Drug-Eluting In-Stent Restenosis: Results From a Patient-Level Pooled Analysis of the RIBS IV and V Trials. AB - BACKGROUND: Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) is more challenging than that of patients with bare-metal stent ISR. However, the results of everolimus-eluting stents (EES) in these distinct scenarios remain unsettled. METHODS AND RESULTS: A pooled analysis of the RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) and RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) randomized trials was performed using patient-level data to compare the efficacy of EES in bare metal stent ISR and DES-ISR. Inclusion and exclusion criteria were identical in both trials. Results of 94 patients treated with EES for bare-metal stent ISR were compared with those of 155 patients treated with EES for DES-ISR. Baseline characteristics were more adverse in patients with DES-ISR, although they presented later and more frequently with a focal pattern. After intervention, minimal lumen diameter (2.22+/-0.5 versus 2.38+/-0.5 mm, P=0.01) was smaller in the DES-ISR group. Late angiographic findings (89.3% of eligible patients), including minimal lumen diameter (2.03+/-0.7 versus 2.36+/-0.6 mm, P<0.001) and diameter stenosis (23+/-22 versus 13+/-17%, P<0.001) were poorer in patients with DES-ISR. Results were consistent in the in-segment and in-lesion analyses. On multiple linear regression analysis, minimal lumen diameter at follow-up remained significantly smaller in patients with DES-ISR. Finally, at 1-year clinical follow-up (100% of patients), mortality (2.6 versus 0%, P<0.01) and need for target vessel revascularization (8 versus 2%, P=0.03) were higher in the DES-ISR group. CONCLUSIONS: This patient-level pooled analysis of the RIBS IV and RIBS V randomized clinical trials suggests that EES provide favorable outcomes in patients with ISR. However, the results of EES are less satisfactory in patients with DES-ISR than in those with bare-metal stent ISR. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01239953 and NCT01239940. PMID- 27412869 TI - Randomized Comparison of a Biodegradable Polymer Ultrathin Strut Sirolimus Eluting Stent With a Biodegradable Polymer Biolimus-Eluting Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT VII Trial. AB - BACKGROUND: Coronary drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy. METHODS AND RESULTS: The Scandinavian Organization for Randomized Trials With Clinical Outcome (SORT OUT) VII trial-a large-scale registry-based randomized, multicenter, single-blind, 2-arm, noninferiority trial-compared 2 biodegradable polymer drug-eluting stents: the thin-strut cobalt-chromium sirolimus-eluting Orsiro stent and the stainless steel biolimus-eluting Nobori stent in an all-comer patient population. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 1 year, analyzed by intention to treat (noninferiority margin of 3.0%). Clinically driven event detection based on Danish registries was used. A total of 1261 patients were assigned to receive the sirolimus-eluting stent (1590 lesions) and 1264 patients to the biolimus-eluting stent (1588 lesions). At 1 year, the composite end point target lesion failure occurred in 48 patients (3.8%) in the sirolimus-eluting group and in 58 patients (4.6%) in the biolimus-eluting group (absolute risk difference, -0.78% [upper limit of 1-sided 95% confidence interval, 0.61%]; P<0.0001). Rates of definite stent thrombosis occurred in 5 (0.4%) of the sirolimus-eluting group compared with 15 (1.2%) biolimus-eluting stent-treated patients (rate ratio, 0.33; 95% confidence interval, 0.12-0.92; P=0.034), which largely was attributable to a lower risk of subacute definite stent thrombosis: 0.1% versus 0.6% (rate ratio, 0.12; 95% confidence interval, 0.02-1.00; P=0.05). CONCLUSIONS: The thin-strut sirolimus eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent in unselected patients for target lesion failure at 1 year. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01879358. PMID- 27412870 TI - Coronary Bioresorbable Vascular Scaffold Use in the Treatment of Coronary Artery Disease. AB - Bioresorbable vascular scaffolds (BVS) represent a promising novel approach for the treatment of coronary artery disease. BVS promise to address some of the well known limitations of current drug-eluting stents, while providing a transient scaffolding of the vessel to prevent acute vessel closure/recoil. Drug elution by BVS prevents neointimal proliferation in a similar fashion to drug-eluting stents, and complete bioresorption is associated with late vessel lumen enlargement, plaque regression, and restoration of vasomotion. Based on the pathophysiological reasons and on the results derived from clinical studies, BVS are increasingly being used in clinical practice. The aim of this review is to provide an overview of the current evidence supporting the use of BVS in clinical practice. In particular, we will discuss the randomized controlled trials and registries evaluating the clinical outcome of these devices, with a special focus on their application in patients with acute coronary syndrome and in specific lesion subsets (bifurcations, chronic total occlusions, and in-stent restenosis). PMID- 27412871 TI - Routine Fractional Flow Reserve Combined to Diagnostic Coronary Angiography as a One-Stop Procedure: Episode 3. PMID- 27412872 TI - In-Stent Restenosis? The Raiders of the Magic Remedy. PMID- 27412873 TI - Increased Circulating Tissue Inhibitor of Metalloproteinase-2 Is Associated With Resistant Hypertension. AB - Resistant hypertension (RH) is associated with organ damage and cardiovascular risk. Evidence suggests the involvement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in hypertension and in cardiovascular remodeling. The aim of this study was to assess the levels of MMP 2 and TIMP-2 in RH and its relation with organ damage, including arterial stiffness and cardiac hypertrophy. MMP-2 and TIMP-2 levels were compared among 19 patients with normotension (NT), 116 with nonresistant hypertension (HTN) and 116 patients with resistant HTN (RH). MMP-2 levels showed no differences among NT, HTN, and RH groups, while TIMP-2 levels were higher in RH compared with HTN and NT groups (90.0 [76.1-107.3] vs 70.1 [57.7-88.3] vs 54.7 [40.9-58.1] ng/mL, P<.01), respectively. MMP-2/TIMP-2 ratio was reduced in the RH group compared with the HTN and NT groups (2.7 [1.9-3.4] vs 3.3 [2.6-4.2] vs 4.9 [4.5-5.3], P<.01), respectively. No associations were found between MMP-2 levels, TIMP-2, and MMP-2/TIMP-2 ratio with cardiac hypertrophy and arterial stiffness in the RH and HTN groups. Finally, in a regression analysis, reduced MMP-2/TIMP-2 ratio and increased TIMP-2 levels were independently associated with RH. The present findings provide evidence that TIMP-2 is associated with RH and might be a possible biomarker for screening RH patients. PMID- 27412874 TI - MicroRNAs in glaucoma and neurodegenerative diseases. AB - MicroRNAs (miRNAs) constitute a class of short, non-coding RNAs, which have important role in post-transcriptional regulation of genes expression by base pairing with their target messenger RNA (mRNA). In recent years, miRNAs biogenesis, gene silencing mechanism and implication in various diseases have been thoroughly investigated. Many scientific findings indicate the altered expression of specific miRNA in the brains of patients affected by neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease and Huntington disease. The progressive optic nerve neuropathy associated with changed miRNA profile was also observed during glaucoma development. This suggests that the miRNAs may have a crucial role in these disorders, contributing to the neuronal cell death. A better understanding of molecular mechanism of these disorders will open a new potential way of ND treatment. In this review, the miRNAs role in particular neurodegenerative disorders and their possible application in medicine was discussed. PMID- 27412875 TI - Block-based association tests for rare variants using Kullback-Leibler divergence. AB - Although genome-wide association studies have successfully detected numerous associations between common variants and complex diseases, these variants typically can only explain a small part of the heritable component of a disease. With the advent of next-generation sequencing, attention has turned to rare variants. Recently, a variety of approaches for detecting associations of rare variants have been proposed, including the Kullback-Leibler divergence-based tests (KLTs) for detecting genotypic differences between cases and controls. However, few of these approaches consider linkage disequilibrium (LD) structure among rare variants and common variants. In this study, we propose two block based association tests for testing the effects of rare variants on a disease. The main idea for this approach comes from the hypothesis that a region of interest may consist of two or more LD blocks such that single-nucleotide variants (SNVs) within each block are correlated, whereas SNVs in different blocks are independent or weakly correlated. Under this hypothesis, we propose two tests that are generalizations of the KLTs by taking the block structure into account. A simulation study under various scenarios shows that the proposed methods have well-controlled type I error rates and outperform some leading methods in the literature. Moreover, application to the Dallas Heart Study data demonstrates the feasibility and performance of the two proposed methods in a realistic setting. PMID- 27412876 TI - Adopting the 'cascade of care' framework: an opportunity to close the implementation gap in addiction care? PMID- 27412877 TI - Role and analysis of monocyte subsets in cardiovascular disease. Joint consensus document of the European Society of Cardiology (ESC) Working Groups "Atherosclerosis & Vascular Biology" and "Thrombosis". AB - Monocytes as cells of the innate immunity are prominently involved in the development of atherosclerotic lesions. The heterogeneity of blood monocytes has widely been acknowledged by accumulating experimental and clinical data suggesting a differential, subset-specific contribution of the corresponding subpopulations to the pathology of cardiovascular and other diseases. This document re-evaluates current nomenclature and summarises key findings on monocyte subset biology to propose a consensus statement about phenotype, separation and quantification of the individual subsets. PMID- 27412878 TI - Effects of Per-diem payment on the duration of hospitalization and medical expenses according to the palliative care demonstration project in Korea. AB - OBJECTIVES: The aim of this study was to examine the impacts of a government directed palliative care demonstration (PCD) project, Per-diem Payment System (PDPS), on length of stay (LOS), hospital costs, resource usage and healthcare quality during the searched period from January in 2009 to December in 2010. STUDY DESIGN: A retrospective claim data review. METHODS: Individuals who had been eligible for the palliative care payment policy, PDPS, during 2 years (from 2009 to 2010) were assigned to the case group including seven hospitals (n = 3117). Those (seven hospitals) who were not come eligible for the palliative care payment policy were assigned to the control group (n = 2347) with fee for service. The data used in this study were electronically submitted requests of payment to the Health Insurance Review Agency during the period January 2009 to December 2010. RESULTS: After the PCD project, the length of stay for palliative patients with cancer diseases decreased by 2.56% (beta = -0.026; p-value = 0.0001) among patients hospitalized in a PCD project compared with patients hospitalized in seven hospitals that was not designed as a PCD project. Compared with costs before the PCD project, costs decreased by 0.76% (beta = 0.013; p value = 0.0001). CONCLUSIONS: We provided evidence regarding the change in the societal burden due to palliative care. Although there was a reduction of direct medical costs reported in limited number of hospitals, in the long term, we can anticipate an expanding impact on medical costs in all palliative hospitals. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27412879 TI - Intimacy between care home residents with dementia: Findings from a review of the literature. AB - BACKGROUND: There is limited research on what family members and frontline care home staff consider to be the best responses to the sexual expression of a person with dementia, whilst at the same time respecting relatives' feelings, managing their possible distress and conflict, and how good practice should be reflected in care home policy and practice guidance. METHODS: This literature review explored what is known of the views of relatives and care workers of new relationships or sexual intimacy between care home residents with dementia, whilst still married to another person. It reports the findings of searches of three databases undertaken in August 2014 (Medline, Embase and PsychINFO). FINDINGS: Nine papers were found relevant to the research question. The following themes emerged from a synthesis of the papers located: sexuality in old age, dementia and sexuality, hyper-sexuality, views regarding sexuality of older people living in care homes, the law, ethics and consent, relationships and communication between care home and relatives, and new relationships or intimacy between residents with dementia. CONCLUSION: While studies of residents' expression of sexuality and their engaging in sexual behaviour with other resident(s) may be challenging to manage in care home settings and can be emotionally painful or uncomfortable for families, the review found that studies are few in number and span emotional intimacy and distressing behaviour. PMID- 27412880 TI - Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models. AB - Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses. PMID- 27412882 TI - ASM Journals Eliminate Impact Factor Information from Journal Websites. PMID- 27412883 TI - Treatment of Crohn's-Related Rectovaginal Fistula With Allogeneic Expanded Adipose Derived Stem Cells: A Phase I-IIa Clinical Trial. AB - : : The aim of this clinical trial was to determine the safety and feasibility of expanded allogeneic adipose-derived stem cells to treat Crohn's-related rectovaginal fistula (CRRVF). We designed a phase I-II clinical trial (https://ClinicalTrials.gov, NCT00999115) to treat 10 patients with CRRVF. Patients receiving biological therapy during follow-up were excluded. Curettage was performed, and a vaginal or rectal flap was added if the surgeon considered it necessary. The therapeutic protocol included intralesional injection of 20 million stem cells in the vaginal walls (submucosal area) and fistula tract. Healing was evaluated 12 weeks later. If the fistula had not healed, a second dose of 40 million stem cells was administered. Patient follow-up was 52 weeks from last cell injection. Healing was defined as re-epithelialization of both vaginal and rectal sides and absence of vaginal drainage. Cytokines and immunological blood tests were monitored. Serious adverse events or rejection issues were not observed. Five patients were excluded because biologic drugs were required to treat a Crohn's disease flare-up during follow-up. Cytokine profiles and immunotoxicity assays showed no statistically significant alterations. Sixty percent of the nonexcluded patients achieved a complete healing. Expanded allogeneic adipose-derived stem-cell injection is a safe and feasible therapy for treating CRRVF, and the healing success rate seems promising (60%). The results of this trial encourage further exploration into this therapy. SIGNIFICANCE: This may be the first publication in which allogeneic stem cells to treat rectovaginal fistula in Crohn's disease seem to be a feasible and safe treatment. Additional studies are necessary to confirm the efficacy profile of the allogeneic stem cells strategy in a controlled design. PMID- 27412884 TI - Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro. AB - : : Bone marrow mesenchymal stromal cells (BM-MSCs) have been characterized and used in many clinical studies based on their immunomodulatory and regenerative properties. We have recently reported the benefit of autologous MSC systemic therapy in the treatment of type 1 diabetes mellitus (T1D). Compared with allogeneic cells, use of autologous products reduces the risk of eliciting undesired complications in the recipient, including rejection, immunization, and transmission of viruses and prions; however, comparable potency of autologous cells is required for this treatment approach to remain feasible. To date, no analysis has been reported that phenotypically and functionally characterizes MSCs derived from newly diagnosed and late-stage T1D donors in vitro with respect to their suitability for systemic immunotherapy. In this study, we used gene array in combination with functional in vitro assays to address these questions. MSCs from T1D donors and healthy controls were expanded from BM aspirates. BM mononuclear cell counts and growth kinetics were comparable between the groups, with equivalent colony-forming unit-fibroblast capacity. Gene microarrays demonstrated differential gene expression between healthy and late-stage T1D donors in relation to cytokine secretion, immunomodulatory activity, and wound healing potential. Despite transcriptional differences, T1D MSCs did not demonstrate a significant difference from healthy controls in immunosuppressive activity, migratory capacity, or hemocompatibility. We conclude that despite differential gene expression, expanded MSCs from T1D donors are phenotypically and functionally similar to healthy control MSCs with regard to their immunomodulatory and migratory potential, indicating their suitability for use in autologous systemic therapy. SIGNIFICANCE: The potential for mesenchymal stromal cells (MSCs) as a cell-based therapy in the treatment of immunologic disorders has been well established. Recent studies reported the clinical potential for autologous MSCs as a systemic therapy in the treatment of type I diabetes mellitus (T1D). The current study compared the genotypic and phenotypic profiles of bone marrow-derived MSCs from T1D and healthy donors as autologous (compared with allogeneic) therapy provides distinct advantages, such as reduced risk of immune reaction and transmission of infectious agents. The findings of the current study demonstrate that despite moderate differences in T1D MSCs at the gene level, these cells can be expanded in culture to an extent corresponding to that of MSCs derived from healthy donors. No functional difference in terms of immunosuppressive activity, blood compatibility, or migratory capacity was evident between the groups. The study findings also show that autologous MSC therapy holds promise as a T1D treatment and should be evaluated further in clinical trials. PMID- 27412885 TI - Toxicity evaluation of alpha-pyrrolidinovalerophenone (alpha-PVP): results from intoxication cases within the STRIDA project. AB - CONTEXT: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving the stimulant NPS alpha-pyrrolidinovalerophenone (alpha-PVP), a potent dopamine re-uptake inhibitor, over a 4-year period. STUDY DESIGN: Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from 2012 to 2015. PATIENTS AND METHODS: In the STRIDA project, blood and urine samples are collected from intoxicated patients with admitted or suspected intake of NPS or unknown drugs presenting to hospitals over the country. Analysis of NPS is performed by mass spectrometry multicomponent methods. Clinical data are collected when caregivers consult the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The severity of poisoning is graded retrospectively using the Poisoning Severity Score (PSS). The inclusion criteria for this study included absence of other stimulants than alpha-PVP. RESULTS: During the 4-year study period, 23 intoxications were originally coded as "alpha-PVP related" out of a total 3743 NPS-related inquiries (0.6%) at the PIC. The present study covered 42 analytically confirmed cases in which alpha-PVP was the only stimulant detected. The age range of patients was 20-58 (median 32) years, of which 79% were males. The alpha-PVP concentration in serum was 4.0-606 (median 64; n = 42) ng/mL and 2.0-41,294 (median 1782; n = 25) ng/mL in urine. There was no statistically significant association between the serum alpha-PVP concentration and urinary alpha-PVP/creatinine ratio in 25 cases, where both sets of data were available. In 14/42 (33%) cases, alpha-PVP was the only psychoactive substance identified. In the remaining cases, additional substances comprised opioids, benzodiazepines, and ethanol. The main clinical manifestations were tachycardia (80%), agitation (70%), hypertension (33%), hallucinations (20%), and delirium (18%). Classification of poisoning severity yielded 25 (60%) moderate (PSS 2), 7 (17%) severe (PSS 3), and 2 fatal cases (PSS 4). CONCLUSIONS: In analytically confirmed alpha-PVP intoxication cases involving no other stimulant drugs, the urine and serum concentrations showed high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results further demonstrated that alpha-PVP prevailed as a drug of abuse after being classified as a narcotic substance, and despite a high incidence of severe poisonings and fatalities. However, the low prevalence of alpha-PVP cases registered at the PIC suggested that many were unaware of the actual substance they had taken. PMID- 27412886 TI - Difference of the clinical course and outcome between dapsone-induced methemoglobinemia and other toxic-agent-induced methemoglobinemia. AB - CONTEXT: Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents. OBJECTIVE: We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents. MATERIALS AND METHODS: A retrospective case-control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included. RESULTS: Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p = 0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p = 0.001, 455 mg vs. 144 mg, p = 0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72 h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia. CONCLUSION: The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia. PMID- 27412881 TI - Evolutionary Ecology of Prokaryotic Immune Mechanisms. AB - Bacteria have a range of distinct immune strategies that provide protection against bacteriophage (phage) infections. While much has been learned about the mechanism of action of these defense strategies, it is less clear why such diversity in defense strategies has evolved. In this review, we discuss the short and long-term costs and benefits of the different resistance strategies and, hence, the ecological conditions that are likely to favor the different strategies alone and in combination. Finally, we discuss some of the broader consequences, beyond resistance to phage and other genetic elements, resulting from the operation of different immune strategies. PMID- 27412887 TI - The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21). AB - Heparin-induced thrombocytopenia is a prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)/heparin complexes. The mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of patients exposed to heparin in some clinical settings is poorly understood. To investigate early events associated with antigen exposure, we first examined the interaction of PF4/heparin complexes with cells circulating in whole blood. In healthy donors, PF4/heparin complexes bind preferentially to B cells (>90% of B cells bind to PF4/heparin in vitro) relative to neutrophils, monocytes, or T cells. Binding of PF4 to B cells is heparin dependent, and PF4/heparin complexes are found on circulating B cells from some, but not all, patients receiving heparin. Given the high proportion of B cells that bind PF4/heparin, we investigated complement as a mechanism for noncognate antigen recognition. Complement is activated by PF4/heparin complexes, co-localizes with antigen on B cells from healthy donors, and is present on antigen-positive B cells in patients receiving heparin. Binding of PF4/heparin complexes to B cells is mediated through the interaction between complement and complement receptor 2 (CR2 [CD21]). To the best of our knowledge, these are the first studies to demonstrate complement activation by PF4/heparin complexes, opsonization of PF4/heparin to B cells via CD21, and the presence of complement activation fragments on circulating B cells in some patients receiving heparin. Given the critical contribution of complement to humoral immunity, our observations provide new mechanistic insights into the immunogenicity of PF4/heparin complexes. PMID- 27412888 TI - A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major. AB - Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelation, reducing myocardial iron uptake. We evaluated whether addition of amlodipine to chelation strategies would reduce myocardial iron overload in TM patients compared with placebo. In a multicenter, double-blind, randomized, placebo-controlled trial, 62 patients were allocated to receive oral amlodipine 5 mg/day or placebo in addition to their current chelation regimen. The main outcome was change in myocardial iron concentration (MIC) determined by magnetic resonance imaging at 12 months, with patients stratified into reduction or prevention groups according to their initial T2* below or above the normal human threshold of 35 ms (MIC, 0.59 mg/g dry weight). At 12 months, patients in the reduction group receiving amlodipine (n = 15) had a significant decrease in MIC compared with patients receiving placebo (n = 15) with a median of -0.26 mg/g (95% confidence interval, -1.02 to -0.01) vs 0.01 mg/g (95% confidence interval, 0.13 to 0.23), P = .02. No significant changes were observed in the prevention group (treatment-effect interaction with P = .005). The same findings were observed in the subgroup of patients with T2* <20 ms. Amlodipine treatment did not cause any serious adverse events. Thus, in TM patients with cardiac siderosis, amlodipine combined with chelation therapy reduced cardiac iron more effectively than chelation therapy alone. Because this conclusion is based on subgroup analyses, it needs to be confirmed in ad hoc clinical trials. This trial was registered at www.clinicaltrials.gov identifier as #NCT01395199. PMID- 27412889 TI - T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. AB - Therapies with novel mechanisms of action are needed for multiple myeloma (MM). B cell maturation antigen (BCMA) is expressed in most cases of MM. We conducted the first-in-humans clinical trial of chimeric antigen receptor (CAR) T cells targeting BCMA. T cells expressing the CAR used in this work (CAR-BCMA) specifically recognized BCMA-expressing cells. Twelve patients received CAR-BCMA T cells in this dose-escalation trial. Among the 6 patients treated on the lowest 2 dose levels, limited antimyeloma activity and mild toxicity occurred. On the third dose level, 1 patient obtained a very good partial remission. Two patients were treated on the fourth dose level of 9 * 10(6) CAR(+) T cells/kg body weight. Before treatment, the first patient on the fourth dose level had chemotherapy resistant MM, making up 90% of bone marrow cells. After treatment, bone marrow plasma cells became undetectable by flow cytometry, and the patient's MM entered a stringent complete remission that lasted for 17 weeks before relapse. The second patient on the fourth dose level had chemotherapy-resistant MM making up 80% of bone marrow cells before treatment. Twenty-eight weeks after this patient received CAR-BCMA T cells, bone marrow plasma cells were undetectable by flow cytometry, and the serum monoclonal protein had decreased by >95%. This patient is in an ongoing very good partial remission. Both patients treated on the fourth dose level had toxicity consistent with cytokine-release syndrome including fever, hypotension, and dyspnea. Both patients had prolonged cytopenias. Our findings demonstrate antimyeloma activity of CAR-BCMA T cells. This trial was registered to www.clinicaltrials.gov as #NCT02215967. PMID- 27412891 TI - Rail-suicide prevention: Systematic literature review of evidence-based activities. AB - BACKGROUND: Rail-related suicide is a relatively rare but extremely lethal method of suicide that can have far-reaching consequences. OBJECTIVE: The aim of the systematic literature review was to analyze the existing literature on the effectiveness of rail-suicide prevention activities. DATA SOURCES: Databases used were Scopus, Medline, and ProQuest. SEARCH TERMS: The search terms used were "suicid*," "prevent*," "rail*," or "train." ELIGIBILITY CRITERIA: English language studies published in peer-reviewed journals between 1 January 1990 and 30 April 2015 that presented an overview of rail-related suicide prevention activities and included an analysis of effectiveness were used. RESULTS: We retrieved 1,229 results in the original search with nine papers presenting empirical evidence. Three studies in the review analyzed the effectiveness of platform screen doors and another three analyzed the installation of blue lights, two papers analyzed the effectiveness of suicide pits, and one included the influence of media reporting guidelines. CONCLUSION: Platform screen doors, suicide pits, blue lights, and improved media guidelines all have the potential to reduce rail-related suicide events and deaths. LIMITATIONS: The review was restricted to English-language peer-reviewed papers published within the chosen time period. PMID- 27412890 TI - Association between gestational weight gain and risk of obesity in preadolescence: a longitudinal study (1997-2007) of 5125 children in Greece. AB - BACKGROUND: The present study aimed to investigate the association between gestational weight gain (GWG) and birth weight, as well as the body mass index (BMI) status, of children at the ages of 2 and 8 years. METHODS: Population-based data were obtained from a database of all 7-9-year-old Greek children who attended primary school during 1997-2007. The study sample consisted of 5125 children matched with their mothers, randomly selected according to region and place of residence, and equally distributed (approximately 500 per year) throughout the study period (1997-2007). A standardised questionnaire was applied; telephone interviews were carried out to collect maternal age, BMI status at the beginning and the end of pregnancy and GWG, birth weight of offspring and BMI status at the ages of 2 and 8 years, as well as several other pregnancy characteristics (e.g. pregnancy duration, gestational medical problems, maternal smoking and alcohol consumption habits, and lactation of offspring after pregnancy). RESULTS: Gestational weight gain was positively associated with the weight status of offspring at all three life stages studied: newborn (birth weight), infant (BMI) and child (BMI) [b = 0.008 (0.001), b = 0.053 (0.009) and b = 0.034 (0.007), respectively, all P < 0.001], after adjusting for maternal age at pregnancy (significant inverse predictor only at age 2 years). The same applied to excessive GWG, as defined by the Institute of Medicine guidelines. CONCLUSIONS: Excessive GWG was associated with a higher risk of greater infant size at birth and a higher BMI status at the ages of 2 and 8 years. Healthcare providers should encourage women to limit their GWG to the range indicated by the current guidelines. PMID- 27412892 TI - Direct TEM observations of growth mechanisms of two-dimensional MoS2 flakes. AB - A microscopic understanding of the growth mechanism of two-dimensional materials is of particular importance for controllable synthesis of functional nanostructures. Because of the lack of direct and insightful observations, how to control the orientation and the size of two-dimensional material grains is still under debate. Here we discern distinct formation stages for MoS2 flakes from the thermolysis of ammonium thiomolybdates using in situ transmission electron microscopy. In the initial stage (400 degrees C), vertically aligned MoS2 structures grow in a layer-by-layer mode. With the increasing temperature of up to 780 degrees C, the orientation of MoS2 structures becomes horizontal. When the growth temperature reaches 850 degrees C, the crystalline size of MoS2 increases by merging adjacent flakes. Our study shows direct observations of MoS2 growth as the temperature evolves, and sheds light on the controllable orientation and grain size of two-dimensional materials. PMID- 27412893 TI - GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity. AB - AIM: Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered. RESULTS: GSNOR null (GSNOR-/-) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR-/- lumbrical muscles showed normal contractility and Ca2+ handling in vitro, suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR-/- TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III, or IV activities. These findings argue that enhanced GSNOR-/- TA contractility is not driven by changes in mitochondrial content or activity, fiber type, or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation, which is believed to increase muscle force output under physiological conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR-/- muscle and was more responsive to agonist (DETANO, BAY 41, and BAY 58) stimulation, suggesting that GSNOR modulates cGMP production in skeletal muscle. INNOVATION: GSNOR may act as a "brake" on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance. CONCLUSIONS: GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification, and sGC activity. Antioxid. Redox Signal. 26, 165-181. PMID- 27412895 TI - Circulating Levels of IL-6 Receptor and gp130 and Long-Term Clinical Outcomes in ST-Elevation Myocardial Infarction. AB - BACKGROUND: Reports on soluble interleukin-6 (IL-6) receptor (sIL-6R) and glycoprotein 130 (sgp130) in ST-elevation myocardial infarction (STEMI) are few and include a small number of patients. The aim of this study was to investigate the possible association between levels of these biomarkers in the acute phase of STEMI and future cardiovascular events. METHODS AND RESULTS: Circulating IL-6, sgp130, sIL-6R, and C-reactive protein (CRP) were measured in 989 STEMI patients during 2007-2011, and cardiovascular events were recorded during follow-up. The primary endpoint was composite of all-cause mortality, myocardial infarction, stroke, unscheduled revascularization, or rehospitalization for heart failure. Cox regression models were used to estimate hazard ratios (HRs) for cardiovascular events in relation to biomarker levels. Median levels of sIL-6R, sgp130, IL-6, and CRP measured 24 hours (median) after symptom onset were 39.2 ng/mL, 240 ng/mL, 18.8 pg/mL, and 13.7 mg/L, respectively. During a median follow up time of 4.6 years, 200 patients (20.2%) experienced a primary endpoint, and 82 patients (8.3%) died. Patients with sIL-6R levels in the upper quartile (>47.7 ng/mL) had significantly higher risk of future adverse events (primary endpoint) and mortality compared to patients with lower levels (adjusted HR, 1.54 [1.08, 2.21]; P=0.02 and 1.81 [1.04, 3.18]; P=0.04, respectively). Neither IL-6 nor sgp130 levels were related to future events, but patients with CRP levels in the upper quartile (>31.5 mg/L) had higher risk of death. CONCLUSION: High levels of sIL-6R were associated with future cardiovascular events and mortality in STEMI patients, suggesting an important role of the IL-6 signaling system. PMID- 27412894 TI - Vitamin D Levels and the Risk of Cognitive Decline in Chinese Elderly People: the Chinese Longitudinal Healthy Longevity Survey. AB - BACKGROUND: Vitamin D has a neuroprotective function, potentially important for the prevention of cognitive decline. Prospective studies from Western countries support an association between lower vitamin D level and future cognitive decline in elderly people. No prospective study has examined this association in Asia. METHODS: This community-based cohort study of elderly people in China follows 1,202 cognitively intact adults aged >=60 years for a mean duration of 2 years. Plasma vitamin D level was measured at the baseline. Cognitive state of participants was assessed using the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as an MMSE score <18. Cognitive decline was defined as >=3 points decline from baseline. Multivariable logistic regression models were used to examine the association between quartiles of vitamin D levels with cognitive decline and incidence of cognitive impairment. RESULTS: Participants with low vitamin D level had an increased risk of cognitive decline. Compared with the highest quartile of vitamin D levels, the multivariable odds ratios (ORs; 95% confidence interval) for cognitive decline were 2.1 (1.3-3.4) for the second highest quartile, 2.2 (1.4-3.6) for the third highest quartile, and 2.0 (1.2-3.3) for the lowest quartile. The multivariable ORs of incident cognitive impairment for the second highest, third highest, and lowest versus highest quartiles of vitamin D levels were 1.9 (0.9-4.1), 2.6 (1.2-5.6), and 3.2 (1.5-6.6), respectively. CONCLUSIONS: This first follow-up study of elderly people, including the oldest-old, in Asia shows that low vitamin D levels were associated with increased risk of subsequent cognitive decline and impairment. PMID- 27412896 TI - High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders. AB - BACKGROUND: The high-fat Western diet is postulated to be associated with the onset and progression of Alzheimer's disease (AD). However, the role of high-fat diet consumption in AD pathology is unknown. This study was undertaken to examine the role of high-fat-diet intake in AD. METHODS AND RESULTS: 5XFAD mice, a useful mouse model of AD, and control wild-type mice were fed (1) high-fat diet or (2) control diet for 10 weeks. The effects on cerebral AD pathology, cognitive function, and metabolic parameters were compared between each group of mice. High fat diet significantly enhanced cerebrovascular beta-amyloid (Abeta) deposition (P<0.05) and impaired cognitive function (P<0.05) in 5XFAD mice, but not in wild type mice. High-fat diet enhanced hippocampal oxidative stress (P<0.05) and NADPH oxidase subunits, gp91(phox) (P<0.01) and p22(phox) (P<0.01) in 5XFAD mice, but not in wild-type mice. Furthermore, high-fat diet reduced cerebral occludin (P<0.05) in 5XFAD mice, but not in wild-type mice. Thus, 5XFAD mice exhibited greater susceptibility to high-fat diet than wild-type mice regarding cerebrovascular injury and cognitive impairment. On the other hand, 5XFAD mice fed high-fat diet exhibited much less increase in body weight, white adipose tissue weight, and adipocyte size than their wild-type counterparts. High-fat diet significantly impaired glucose tolerance in wild-type mice but not in 5XFAD mice. Thus, 5XFAD mice had much less susceptibility to high-fat-diet-induced metabolic disorders than wild-type mice. CONCLUSIONS: High-fat diet, independently of metabolic disorders, significantly promotes the progression of AD-like pathology through enhancement of cerebral amyloid angiopathy and oxidative stress. PMID- 27412897 TI - Transcatheter Aortic Valve Implantation With or Without Preimplantation Balloon Aortic Valvuloplasty: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Preimplantation balloon aortic valvuloplasty (BAV) is considered a routine procedure during transcatheter aortic valve implantation (TAVI) to facilitate prosthesis implantation and expansion; however, it has been speculated that fewer embolic events and/or less hemodynamic instability may occur if TAVI is performed without preimplantation BAV. The aim of this study was to systematically review the clinical outcomes associated with TAVI undertaken without preimplantation BAV. METHODS AND RESULTS: We conducted a search of Medline and Embase to identify studies that evaluated patients who underwent TAVI with or without preimplantation BAV for predilation. Pooled analysis and random effects meta-analyses were used to estimate the rate and risk of adverse outcomes. Sixteen studies involving 1395 patients (674 with and 721 without preimplantation BAV) fulfilled the inclusion criteria. Crude device success was achieved in 94% (1311 of 1395), and 30-day all-cause mortality occurred in 6% (72 of 1282) of patients. Meta-analyses evaluating outcomes of strategies with and without preimplantation BAV showed no statistically significant differences in terms of mortality (relative risk [RR] 0.61, 95% CI 0.32-1.14, P=0.12), safety composite end point (RR 0.85, 95% CI 0.62-1.18, P=0.34), moderate to severe paravalvular leaks (RR 0.68, 95% CI 0.23-1.99, P=0.48), need for postdilation (RR 0.86, 95% CI 0.66-1.13, P=0.58), stroke and/or transient ischemic attack (RR 0.72, 95% CI 0.30-1.71, P=0.45), and permanent pacemaker implantation (RR 0.80, 95% CI 0.49-1.30, P=0.37). CONCLUSIONS: Our analysis suggests that TAVI procedures with or without preimplantation BAV were associated with similar outcomes for a number of clinically relevant end points. Further studies including a large number of patients are needed to ascertain the impact of TAVI without preimplantation BAV as a standard practice. PMID- 27412898 TI - Change in Angina Symptom Status After Acute Myocardial Infarction and Its Association With Readmission Risk: An Analysis of the Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) Registry. AB - BACKGROUND: Angina is common both before and after myocardial infarction (MI). Whether the change in angina status within the first 30 days after MI is associated with subsequent readmission and angina persistence is unknown. METHODS AND RESULTS: We studied 2915 MI patients enrolled at 24 hospitals in the Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registry. Angina before and 30 days after MI was assessed with the Seattle Angina Questionnaire. Patients were divided into angina-free pre- and post-MI (-/-), resolved angina (+/-), new angina (-/+), and persistent angina (+/+) groups. Multivariable proportional hazards and hierarchical modified Poisson models were performed to assess the association of each group with all-cause readmission, readmission for MI or unplanned revascularization, and angina persistence at 1 year. Overall, 1293 patients (44%) had angina before their MI and 849 (29%) reported angina within 30 days of discharge. Patients with post-MI angina were more likely to be younger, nonwhite, and uninsured. Compared with patients who were angina-free pre- and post-MI, 1-year all-cause readmission risks were significantly higher for patients with persistent angina (hazard ratio [HR], 1.35; 95% CI 1.06-1.71) or new angina (HR, 1.40; 95% CI, 1.08-1.82). At 1 year, angina was present in 22% of patients and was more likely if angina was persistent (HR, 3.55; 95% CI, 3.05 4.13) or new (HR, 3.38; 95% CI, 2.59-4.42) at 30 days compared with patients who were angina-free pre- and post-MI. CONCLUSIONS: Post-MI angina, whether new or persistent, is associated with higher likelihood of readmission. Prioritizing post-MI angina management is a potential means of improving 1-year outcomes. PMID- 27412899 TI - Coronary Computed Tomography (CT) Angiography as a Predictor of Cardiac and Noncardiac Vascular Events in Asymptomatic Type 2 Diabetics: A 7-Year Population Based Cohort Study. AB - BACKGROUND: Type 2 diabetics are at increased risk for vascular events, but the value of further risk stratification for coronary heart disease (CHD) in asymptomatic subjects is unclear. We examined the added value of coronary computed tomography angiography over clinical risk scores (United Kingdom Prospective Diabetes Study), and coronary artery calcium in a population-based cohort of asymptomatic type 2 diabetics. METHODS AND RESULTS: Subjects (n=630) underwent baseline clinical assessment and computed tomography angiography (64 slice scanner). Plaque site, volume, calcific content, and arterial remodeling were recorded using dedicated software. Coronary, macrovascular, and microvascular-related events were assessed over 6.6+/-0.6 (mean+/-SD) (range 5.4 7.5) years and all CHD events were adjudicated. Discrimination of CHD events (cardiovascular death, myocardial infarction, unstable angina, or new-onset angina requiring intervention) (n=41) was improved by addition of total plaque burden to the clinical risk and coronary artery calcium scores combined (C=0.789 versus 0.763, P=0.034) and further improved by addition of an angiographic score (C=0.824, P=0.021). Independent predictors of a CHD event were United Kingdom Prospective Diabetes Study risk score (hazard ratio 1.3 per 10% 10-year risk, P=0.003) and the angiographic score (hazard ratio 3.2 per quartile, P<0.0001). Classification was improved over that by United Kingdom Prospective Diabetes Study and coronary artery calcium scores alone (overall net reclassification improvement 0.24). In subjects with coronary plaque (N=500), mild plaque calcification independently predicted a CHD event (hazard ratio 3.0, P=0.02). Computed tomography angiography predicted combined macrovascular but not microvascular-related events. CONCLUSIONS: Computed tomography angiography provides additional prognostic information in asymptomatic type 2 diabetics not obtainable from clinical risk assessment and coronary artery calcium alone. PMID- 27412901 TI - Leisure Time Physical Activity and Cardio-Metabolic Health: Results From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). AB - BACKGROUND: Although increasing effort has been devoted to the promotion of a healthy lifestyle such as leisure time physical activity for cardio-metabolic health, specific evidence supporting health policy remains sparse, particularly in those ethnically diverse populations where cardio-metabolic diseases are reaching epidemic proportion and yet are grossly understudied. METHODS AND RESULTS: We conducted a cross-sectional analysis of the baseline data from 10 585 participants aged 35 to 74 free of cardiovascular diseases in the Brazilian Longitudinal Study of Adult Health. Leisure time physical activity status was defined by the American Heart Association and the World Health Organization recommendations (>=150 min/week moderate activities or 75 min/week vigorous activities). In total, 1183 (21%) women and 1387 (29%) men were active. After accounting for covariates, the favorable effects of leisure time physical activity on cardio-metabolic parameters were evident. Specifically, the average blood pressure, heart rate, and Framingham Risk Score for cardiovascular diseases of the active were significantly lower within each sex. The ORs comparing the active versus the inactive women were 0.78 (95% CI: 0.66-0.92) for hypertension and 0.78 (95% CI: 0.65-0.93) for cardiovascular diseases in 10 years. Among men, the ORs were 0.75 (95% CI: 0.65-0.87) for hypertension and 0.73 (95% CI: 0.61 0.87) for diabetes. The 10-year risk of cardiovascular diseases was significantly lower among the active men with a 33% reduction (OR=0.67, 95% CI: 0.57-0.78). CONCLUSIONS: We observed beneficial effects of leisure time physical activity on cardio-metabolic health in this large Brazilian population that are consistent with studies in North America and Europe. PMID- 27412900 TI - Monosialoganglioside-Containing Nanoliposomes Restore Endothelial Function Impaired by AL Amyloidosis Light Chain Proteins. AB - BACKGROUND: Light chain amyloidosis (AL) is associated with high mortality, especially in patients with advanced cardiovascular involvement. It is caused by toxicity of misfolded light chain proteins (LC) in vascular, cardiac, and other tissues. There is no treatment to reverse LC tissue toxicity. We tested the hypothesis that nanoliposomes composed of monosialoganglioside, phosphatidylcholine, and cholesterol (GM1 ganglioside-containing nanoliposomes [NLGM1]) can protect against LC-induced human microvascular dysfunction and assess mechanisms behind the protective effect. METHODS AND RESULTS: The dilator responses of ex vivo abdominal adipose arterioles from human participants without AL to acetylcholine and papaverine were measured before and after exposure to LC (20 MUg/mL) with or without NLGM1 (1:10 ratio for LC:NLGM1 mass). Human umbilical vein endothelial cells were exposed for 18 to 20 hours to vehicle, LC with or without NLGM1, or NLGM1 and compared for oxidative and nitrative stress response and cellular viability. LC impaired arteriole dilator response to acetylcholine, which was restored by co-treatment with NLGM1. LC decreased endothelial cell nitric oxide production and cell viability while increasing superoxide and peroxynitrite; these adverse effects were reversed by NLGM1. NLGM1 increased endothelial cell protein expression of antioxidant enzymes heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 and increased nuclear factor, erythroid 2 like 2 (Nrf-2) protein. Nrf-2 gene knockdown reduced antioxidant stress response and reversed the protective effects of NLGM1. CONCLUSIONS: NLGM1 protects against LC induced human microvascular endothelial dysfunction through increased nitric oxide bioavailability and reduced oxidative and nitrative stress mediated by Nrf 2-dependent antioxidant stress response. These findings point to a potential novel therapeutic approach for light chain amyloidosis. PMID- 27412902 TI - No Decline in the Risk of Stroke Following Incident Atrial Fibrillation Since 2000 in the Community: A Concerning Trend. AB - BACKGROUND: While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce. METHODS AND RESULTS: Olmsted County, MN residents with incident atrial fibrillation or atrial flutter (collectively referred to as AF) from 2000 to 2010 were identified. Cox regression determined associations of year of AF diagnosis with ischemic stroke and transient ischemic attack (TIA) occurring through 2013. Among 3247 AF patients, 321 (10%) had an ischemic stroke/TIA over a mean of 4.6 years (incidence rate [95% CI] per 100 person years: 2.14 [1.91-2.38]). Two hundred thirty-nine (7%) of 3265 AF patients experienced an ischemic stroke (incidence rate: 1.54 [1.35-1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95% CI] per year of AF diagnosis: 1.00 [0.96-1.04] for ischemic stroke/TIA; 1.01 [0.96-1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after AF diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95% CI] per year of AF diagnosis: 1.06 [0.97-1.15] for ischemic stroke/TIA; 1.08 [0.98-1.20] for ischemic stroke only). CONCLUSIONS: Strokes/TIAs are frequent after AF, occurring in 10% of patients after 5 years of follow-up. The occurrence of stroke/TIA did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications. PMID- 27412903 TI - ECG Criteria to Differentiate Between Takotsubo (Stress) Cardiomyopathy and Myocardial Infarction. AB - BACKGROUND: ECG criteria differentiating Takotsubo cardiomyopathy (TTC) from mainly anterior myocardial infarction (MI) have been suggested; however, this was in small patient populations. METHODS AND RESULTS: Twelve-lead admission ECGs of consecutive 200 TTC and 200 MI patients were compared in dichotomized groups based on the presence or absence of ST-elevation MI (STEMI versus STE-TTC and non ST elevation MI versus non ST-elevation-TTC). When comparing STEMI and STE-TTC, ST-elevation in -aVR was characteristic of STE-TTC with a sensitivity/specificity of 43% and 95%, positive predictive value (PPV) 91%, and a negative predictive value (NPV) 62% (P<0.001); when ST-elevation in -aVR is accompanied by ST elevation in inferior leads, sensitivity/specificity were 14% and 98% (PPV was 89% and NPV 52%) (P=0.001), and 12% and 100% when associated with ST-elevation in anteroseptal leads (PPV 100%, NPV 52%) (P<0.001). On the other hand, STEMI was characterized by ST-elevation in aVR (sensitivity/specificity of 31% and 95% P<0.001, PPV 85% and NPV 59%) and ST-depression in V2-V3-V4 (sensitivity/specificity of 24% and 100% P<0.001, PPV 100% and NPV 76%). When comparing non-ST elevation MI and non ST-elevation-TTC, T-inversion in leads I aVL-V5-V6 had a sensitivity/specificity of 17% and 97% for non ST-elevation-TTC (PPV 83% and NPV 55%) (P<0.001), and ST-elevation in -aVR with T-inversion in any lead was also specific for non ST-elevation-TTC (sensitivity/specificity of 8% and 100%, PPV 100% and NPV 53%) (P=0.006). In non-ST elevation MI patients, the presence of ST-depression in V2-V3 was specific (sensitivity/specificity of 11% and 99%, PPV 91% and NPV 51%) (P=0.01). CONCLUSIONS: ECG on admission can differentiate between TTC and acute MI, with high specificity and positive predictive value. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01947621. PMID- 27412904 TI - Sedation in the Electrophysiology Laboratory: A Multidisciplinary Review. PMID- 27412907 TI - Is successful orthotopic heart transplantation in the pig-to-non-human primate model required before proceeding to a clinical trial? PMID- 27412906 TI - Minnesota Resuscitation Consortium's Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital Refractory Ventricular Fibrillation. AB - BACKGROUND: In 2015, the Minnesota Resuscitation Consortium (MRC) implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out-of-hospital refractory ventricular fibrillation/ventricular tachycardia (VF/VT). We report the outcomes of the initial 3-month period of operations. METHODS AND RESULTS: Three emergency medical services systems serving the Minneapolis-St. Paul metro area participated in the protocol. Inclusion criteria included age 18 to 75 years, body habitus accommodating automated Lund University Cardiac Arrest System (LUCAS) cardiopulmonary resuscitation (CPR), and estimated transfer time from the scene to the cardiac catheterization laboratory of <=30 minutes. Exclusion criteria included known terminal illness, Do Not Resuscitate/Do Not Intubate status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained return of spontaneous circulation after treatment with 3 direct current shocks and administration of 300 mg of intravenous/intraosseous amiodarone. Patients were transported to the University of Minnesota, where emergent advanced perfusion strategies (extracorporeal membrane oxygenation; ECMO), followed by coronary angiography and primary coronary intervention (PCI), were performed, when appropriate. Over the first 3 months of the protocol, 27 patients were transported with ongoing mechanical CPR. Of these, 18 patients met the inclusion and exclusion criteria. ECMO was placed in 83%. Seventy-eight percent of patients had significant coronary artery disease with a high degree of complexity and 67% received PCI. Seventy-eight percent of patients survived to hospital admission and 55% (10 of 18) survived to hospital discharge, with 50% (9 of 18) achieving good neurological function (cerebral performance categories 1 and 2). No significant ECMO-related complications were encountered. CONCLUSIONS: The MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications. PMID- 27412905 TI - Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation. AB - BACKGROUND: The introduction of non-vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. METHODS AND RESULTS: Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46-0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76-1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72-1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34-0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67-0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90-1.20], P=0.60). All non-vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. CONCLUSIONS: In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin. PMID- 27412908 TI - Plasmonic nanohalo optical probes for highly sensitive imaging of survivin mRNA in living cells. AB - A strategy is designed for sensitive detection of tumor biomarker survivin mRNA based on resonance Rayleigh scattering of a single AuNP nanohalo probe that couples large gold nanoparticles (L-AuNPs, 52 nm) with small AuNPs (S-AuNPs, 18 nm) through the affinity interaction between streptavidin and biotin. This core satellite plasmon ruler is further applied to imaging survivin mRNA in living cells. PMID- 27412909 TI - Pharmacokinetics, metabolism, and excretion of cycloastragenol, a potent telomerase activator in rats. AB - 1. The objective of this study was to investigate the pharmacokinetics, excretion, and metabolic fate of cycloastragenol (CA) in rats. 2. An LC-MS method was developed and used to quantify CA in biological samples. Rats were orally administrated with CA at 10, 20, and 40 mg/kg or intravenously administrated at 10 mg/kg to determine pharmacokinetic parameters of CA. For excretion experiment, urine, feces, and bile were collected at 24 h after oral administration (40 mg/kg), also at 12 h after intravenous administration (10 mg/kg). An LC-MS/MS method was developed to identify the metabolites of CA. 3. The results showed that the oral bioavailability of CA was about 25.70% at 10 mg/kg. CA was excreted through bile and feces and eliminated predominantly by the kidney in rats. It also might exist an enterohepatic circulation of CA in rats. CA could be metabolized widely in vivo in rat, seven, six, and one phase I metabolites were found in feces, urine, and bile samples respectively, but no phase II metabolite was found. 4. In summary, this study defined pharmacokinetics characteristics of CA, described its excretion, and established its in vivo metabolism in rats. PMID- 27412910 TI - Variation of DNA methylation patterns associated with gene expression in rice (Oryza sativa) exposed to cadmium. AB - We report genome-wide single-base resolution maps of methylated cytosines and transcriptome change in Cd-exposed rice. Widespread differences were identified in CG and non-CG methylation marks between Cd-exposed and Cd-free rice genomes. There are 2320 non-redundant differentially methylated regions detected in the genome. RNA sequencing revealed 2092 DNA methylation-modified genes differentially expressed under Cd exposure. More genes were found hypermethylated than those hypomethylated in CG, CHH and CHG (where H is A, C or T) contexts in upstream, gene body and downstream regions. Many of the genes were involved in stress response, metal transport and transcription factors. Most of the DNA methylation-modified genes were transcriptionally altered under Cd stress. A subset of loss of function mutants defective in DNA methylation and histone modification activities was used to identify transcript abundance of selected genes. Compared with wide type, mutation of MET1 and DRM2 resulted in general lower transcript levels of the genes under Cd stress. Transcripts of OsIRO2, OsPR1b and Os09g02214 in drm2 were significantly reduced. A commonly used DNA methylation inhibitor 5-azacytidine was employed to investigate whether DNA demethylation affected physiological consequences. 5-azacytidine provision decreased general DNA methylation levels of selected genes, but promoted growth of rice seedlings and Cd accumulation in rice plant. PMID- 27412911 TI - DNA damage induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes beta-catenin-mediated invasion. AB - DNA damage induced apoptosis suppressor (DDIAS) is an anti-apoptotic protein that promotes cancer cell survival. We previously reported that DDIAS is transcriptionally activated by nuclear factor of activated T cells 2 (NFATc1). However, the upstream regulation of DDIAS expression by growth factors has not been studied. Here, we demonstrate that DDIAS expression is induced by extracellular signal-regulated kinase 5 (ERK5) and myocyte enhancer factor 2B (MEF2B) in response to epidermal growth factor (EGF) and that it positively regulates beta-catenin signaling in HeLa cells. The genetic or pharmacological inhibition of ERK5 suppressed DDIAS induction following EGF exposure and the overexpression of constitutively active MEK5 (CA-MEK5) enhanced DDIAS expression. In chromatin immunoprecipitation assays, MEF2B, a downstream target of ERK5, exhibited sequence-specific binding to a MEF2 binding site in the DDIAS promoter following treatment with EGF. The overexpression of MEF2B increased the EGF mediated induction of DDIAS expression, whereas the knockdown of MEF2B impaired this effect. Furthermore, DDIAS promoted invasion by increasing beta-catenin expression at the post-translational level in response to EGF, suggesting that DDIAS plays a crucial role in the metastasis of cancer cells by regulating beta catenin expression. It is unlikely that MEF2B and NFATc1 cooperatively regulate DDIAS transcription in response to EGF. Collectively, EGF activates the ERK5/MEF2 pathway, which in turn induces DDIAS expression to promote cancer cell invasion by activating beta-catenin target genes. PMID- 27412912 TI - Transcriptional and post-transcriptional control of the plant circadian gene regulatory network. AB - The circadian clock drives rhythms in multiple physiological processes allowing plants to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of thousands of genes linked to the control of photosynthesis, cell elongation, biotic and abiotic stress responses, developmental processes such as flowering, and the clock itself. Given its pervasive effects on plant physiology, it is not surprising that circadian clock genes have played an important role in the domestication of crop plants and in the improvement of crop productivity. Therefore, identifying the principles governing the dynamics of the circadian gene regulatory network in plants could strongly contribute to further speed up crop improvement. Here we provide an historical as well as a current description of our knowledge of the molecular mechanisms underlying circadian rhythms in plants. This work focuses on the transcriptional and post-transcriptional regulatory layers that control the very core of the circadian clock, and some of its complex interactions with signaling pathways that help synchronize plant growth and development to daily and seasonal changes in the environment. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer. PMID- 27412913 TI - Histone variants in plant transcriptional regulation. AB - Chromatin based organization of eukaryotic genome plays a profound role in regulating gene transcription. Nucleosomes form the basic subunits of chromatin by packaging DNA with histone proteins, impeding the access of DNA to transcription factors and RNA polymerases. Exchange of histone variants in nucleosomes alters the properties of nucleosomes and thus modulates DNA exposure during transcriptional regulation. Growing evidence indicates the important function of histone variants in programming transcription during developmental transitions and stress response. Here we review how histone variants and their deposition machineries regulate the nucleosome stability and dynamics, and discuss the link between histone variants and transcriptional regulation in plants. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer. PMID- 27412914 TI - Skill decay or maintenance between tourniquet uses among first aid caregivers: Exploration in a manikin model. PMID- 27412915 TI - An ED pilot intervention to facilitate outpatient acute care for cancer patients. AB - INTRODUCTION: Unplanned hospitalizations are common in patients with cancer, and most hospitalizations originate in the emergency department (ED). METHODS: We implemented an ED-based pilot intervention designed to reduce hospitalizations among patients with solid tumors. The intervention, piloted at a single academic medical center, involved a medical oncologist embedded in the ED during evening hours. We used a quasiexperimental preimplementation/postimplementation study design to evaluate the proportion of ED visits that resulted in inpatient hospital admission, before and after pilot implementation. General estimating equations were used to evaluate the association between the intervention and hospital admission. RESULTS: There were 390 ED visits by eligible cancer patients in the preintervention period and 418 visits in the intervention period. During the intervention period, 158 (38%) of 418 ED visits were identified by the embedded oncologist during the evening intervention shift. The proportion of ED visits leading to hospitalization was 70% vs 69% in the preintervention and intervention periods (odds ratio, 0.93 [95% confidence interval, 0.69-1.24]; P= .62). There were no differences between periods in ED length of stay or subsequent use of acute care. Among patients with initial ED presentation during the operating hours of the intervention, the proportion of ED visits leading to hospitalization was 77% vs 67% in the preintervention and intervention periods (odds ratio, 0.62 [0.36-1.08]; P= .08). CONCLUSION: Embedding an oncologist in the ED of an academic medical center did not significantly reduce hospital admissions. Novel approaches are needed to strengthen outpatient acute care for patients with cancer. PMID- 27412917 TI - ID4 controls luminal lineage commitment in normal mammary epithelium and inhibits BRCA1 function in basal-like breast cancer. AB - Inhibitor of differentiation (ID) proteins are key regulators of development and tumorigenesis. One member of this family, ID4, controls lineage commitment during mammary gland development by acting upstream of key developmental pathways. Recent evidence suggests an emerging role for ID4 as a lineage-dependent proto oncogene that is overexpressed and amplified in a subset of basal-like breast cancers (BLBCs), conferring poor prognosis. Several lines of evidence suggest ID4 may suppress BRCA1 function in BLBC and in doing so, define a subset of BLBC patients who may respond to therapies traditionally used in BRCA1-mutant cancers. This review highlights recent advances in our understanding of the requirement for ID4 in mammary lineage commitment and the role for ID4 in BLBC. We address current shortfalls in this field and identify important areas of future research. PMID- 27412916 TI - Acute coagulopathy after multiple blunt injuries in a case of hemophilia A consideration for pathophysiology of coagulopathy. PMID- 27412919 TI - Porous Azo-Bridged Porphyrin-Phthalocyanine Network with High Iodine Capture Capability. AB - We report a highly efficient iodine adsorbent achieved by rational design of a porous azo-bridged porphyrin-phthalocyanine network (AzoPPN), which was synthesized by a catalyst-free coupling reaction between free-base 5,10,15,20 tetrakis(4-nitrophenyl)-porphyrin and nickel tetraaminophthlocyanine. AzoPPN has a permanent porous structure and plenty of porphyrin and phthalocyanine units in the skeleton as effective sorption sites. It displays excellent adsorption of iodine vapor up to 290 wt. % and also shows remarkable capability as adsorbent for iodine in solution. This strategy of combining physisorption with chemisorption in one adsorbent will pave the way for the development of new materials for iodine capture. PMID- 27412918 TI - Effect of paternal overweight or obesity on IVF treatment outcomes and the possible mechanisms involved. AB - Leukocyte telomere lengths (LTLs) are shorter in obese compared with normal weight people. However, it is not known whether sperm telomere length (STL) is related to obesity. The aim of the study was to evaluate the impact of men's body mass index (BMI) on STL, embryo quality, and clinical outcomes in couples undergoing IVF. In total, 651 couples were recruited, including 345 men with a normal BMI and 306 men with an overweight BMI (normal BMI group: 20-25 kg/m(2); overweight BMI group: >28 kg/m(2)). We found that couples with male's BMI over 28 kg/m(2) exhibited a significantly lower fertilization rate, good-quality embryo rate and clinical pregnancy rate compared to their normal BMI counterparts. The mean STL in the overweight BMI group was also significantly shorter than that of the normal BMI group. The results also showed that individuals with higher BMI had higher ROS (Reactive oxygen species) content and sperm DNA fragmentation rate when compared with normal BMI individuals. Mitochondrial activity was also lower in the overweight BMI group than in the normal BMI group. This is the first report to find that STL is shorter in overweight/obese men, which may account for their poorer treatment outcomes in IVF cycles. PMID- 27412920 TI - Update on management of epilepsy in women for the non-neurologist. AB - Epilepsy is a common neurological disorder, prevalent in about 1% of the population. Almost half of the patients with epilepsy are women. Epilepsy and antiepileptic drugs can affect each aspect of the female human life cycle which includes menstrual cycle, contraception, fertility, conception, pregnancy and menopause. The interplay of the female hormonal state and epilepsy is complex and has to be taken in to consideration when managing their epilepsy. This review focuses on the management of women with epilepsy related to their role in reproduction. PMID- 27412922 TI - Intracellular Delivery and Triggered Release of DNA Using Biodegradable Poly(2 hydroxypropylene imine)s Containing Cystamine Units. AB - Poly(2-hydroxypropylene imine)s containing segments of cystamine (PHPI-CA) are synthesized by polycondensation of 1,3-dibromo-2-propanol with a mixture of 1,3 diamino-2-propanol and cystamine. High molecular weight fractions of these polymers are collected by ultrafiltration and characterized by chemical analysis, 1 H and 13 C-NMR spectroscopy, size-exclusion chromatography with triple detection, and potentiometric titration, and are tested for DNA delivery in vitro. It is shown that PHPI-CA are highly branched polymers containing disulfide linkages. Transfection efficiency of PHPI-CA for DNA gives similar results to that of PHPI with GFP+ cell percent reaching 80-90%. Cytotoxicity levels for PHPI CA are lower than that of PHPI. Novel polymers containing different amounts of disulfide linkages are able to disintegrate and release DNA following the treatment with reducing agent 1,4-dithiothreitol. Downstream application of PHPI CA transfected cells for RNA purification shows that RNA yield is not affected even after the double transfection suggesting that these polymers could be great candidates for in vitro and in vivo transfection. PMID- 27412923 TI - Interankle Systolic Blood Pressure Difference Is a Marker of Prevalent Stroke in Chinese Adults: A Cross-Sectional Study. AB - This cross-sectional study carried out from November 2014 to December 2014 aimed to determine whether the interankle systolic blood pressure (SBP) difference is an independent marker of prevalent stroke. Simultaneous four-limb blood pressure measurements (oscillometric devices) and calculated SBP difference between the lower limbs were collected from 1485 participants aged 35 years and older. Questionnaires about traditional stroke risk factors were completed. Interankle SBP difference >=7 mm Hg was independently associated with a history of stroke after adjusting for traditional stroke risk factors (odds ratio, 1.64; 95% confidence interval, 1.53-3.59; P=.0123). Net reclassification improvement analysis showed that adding the interankle SBP difference to traditional risk factors improved the predictive ability for stroke risk by 18.5% (P<.001). In conclusion, an interankle SBP difference >=7 mm Hg could be an independent marker of stroke history in Chinese adults. It could offer an extra benefit in identifying individuals with risk of stroke beyond conventional clinical features. PMID- 27412924 TI - The emotional health and well-being of Canadians who care for persons with mental health or addictions problems. AB - The purpose of this project was to examine the emotional health and well-being of Canadian caregivers of persons with significant mental health or addictions problems. We assessed the emotional health of caregivers by care-receiver condition type (i.e. mental health or addictions vs. physical or other health problems), levels of caregiver stress and methods particularly for reducing stress among caregivers of persons with mental health or addictions disorders. Weighted cross-sectional data from the 2012 General Social Survey (Caregiving and Care Receiving) were modelled using weighted descriptive and logistic regression analyses to examine levels of stress and the emotional health and well-being of caregivers by care-receiver condition type. Caregivers of persons with mental health or addictions problems were more likely to report that caregiving was very stressful and that they felt depressed, tired, worried or anxious, overwhelmed; lonely or isolated; short-tempered or irritable; and resentful because of their caregiving responsibilities. The results of this study suggest that mental health and addictions caregivers may experience disparate stressors and require varying services and supports relative to caregivers of persons with physical or other health conditions. PMID- 27412925 TI - Acetylome analysis reveals the involvement of lysine acetylation in diverse biological processes in Phytophthora sojae. AB - Lysine acetylation is a dynamic and highly conserved post-translational modification that plays an important regulatory role in almost every aspects of cell metabolism in both eukaryotes and prokaryotes. Phytophthora sojae is one of the most important plant pathogens due to its huge economic impact. However, to date, little is known about the functions of lysine acetylation in this Phytopthora. Here, we conducted a lysine acetylome in P. sojae. Overall, 2197 lysine acetylation sites in 1150 proteins were identified. The modified proteins are involved in diverse biological processes and are localized to multiple cellular compartments. Importantly, 7 proteins involved in the pathogenicity or the secretion pathway of P. sojae were found to be acetylated. These data provide the first comprehensive view of the acetylome of P. sojae and serve as an important resource for functional analysis of lysine acetylation in plant pathogens. PMID- 27412926 TI - Delays during the administration of acetylcysteine for the treatment of paracetamol overdose. AB - BACKGROUND: The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. METHOD: A 6-month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. RESULTS: From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50-163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217-413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95-260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. CONCLUSION: Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge. PMID- 27412927 TI - [Effects of IFN-gamma treatment on biological characteristics and functions of dendritic cells]. AB - Objective To investigate the effect of IFN-gamma treatment on the biological characteristics and functions of C57BL/6 murine dendritic cells (DCs). Methods In the process of DC culture, 20 ng/mL IFN-gamma was added in the DCs at the early (day 2) or late (day 5) stage, and on day 7, LPS was added to stimulate DC maturation. The expressions of DC surface molecules CD11c, CD80 and CD86 were determined by flow cytometry. To analyze cell functions, DCs were co-cultured with BALB/c mouse-derived lymphocyte cells. The 5, 6-carboxyfluorescein diacetate N-succinimidyl ester (CFSE) labelling was used to detect their ability to stimulate allogeneic lymphocyte proliferation and flow cytometry was used to measure their ability to induce the production of regulatory T cells (Tregs). Results Compared with the control group, the early IFN-gamma treatment group had decreased DC number and inhibited cell differentiation; though there was no difference in the expression of co-stimulatory molecules, early IFN-gamma treatment resisted the stimulatory effect of LPS on DC maturation, weakened the ability to stimulate allogeneic lymphocyte proliferation and enhanced the ability to induce more Tregs. Compared with the control group, the late IFN-gamma treatment group showed no change in DC number and differentiation; the expressions of co-stimulatory molecules CD86 and CD80 were upregulated; the results of DC maturation and mixed allogeneic lymphocyte reaction stimulated by LPS were similar to those in the control group, but its ability to induce Tregs was stronger. Conclusion DCs treated with IFN-gamma at early stage and those at late stage showed obvious difference in biological characteristics and functions. PMID- 27412928 TI - [Knockdown of PRDX6 in microglia reduces neuron viability after OGD/R injury]. AB - Objective To observe the effects of peroxiredoxin 6 (PRDX6) knockdown in the microglia on neuron viability after oxygen-glucose deprivation and reoxygenation (OGD/R). Methods Microglia was treated with lentivirus PRDX6-siRNA and Ca(2+) independent phospholipase A2 (iPLA2) inhibitor, 1-hexadecyl-3-(trifluoroethgl)-sn glycerol-2 phosphomethanol (MJ33). Twenty-four hours later, it was co-cultured with primary neuron to establish the microglia-neuron co-culture OGD/R model. According to the different treatment of microglia, the cells were divided into normal group, OGD/R group, negative control-siRNA treated OGD/R group, PRDX6 siRNA treated OGD/R group and PRDX6-siRNA combined with MJ33 treated OGD/R group. Western blot analysis and real-time quantitative PCR were respectively performed to detect PRDX6 protein and mRNA levels after knockdown of PRDX6 in microglia. The iPLA2 activity was measured by ELISA. MTS and lactate dehydrogenase (LDH) assay were used to measure neuron viability and cell damage. The oxidative stress level of neuron was determined by measuring superoxide dismutase (SOD) and malonaldehyde (MDA) content. Results In PRDX6-siRNA group, neuron viability was inhibited and oxidative stress damage was aggravated compared with OGD/R group. In PRDX6-siRNA combined with MJ33 group, cell viability was promoted and oxidative stress damage was alleviated compared with PRDX6-siRNA group. Conclusion PRDX6 in microglia protects neuron against OGD/R-induced injury, and iPLA2 activity has an effect on PRDX6. PMID- 27412929 TI - [Isolation and purification of primary Kupffer cells from mouse liver]. AB - Objective To isolate and purify Kupffer cells (KCs) from BALB/c mice by an efficient method of low-speed centrifugation and rapid adherence. Methods The mouse liver tissue was perfused in situ and digested with 0.5 g/L collagenase type IV in vitro by water bath. Then, through the low-speed centrifugation, KCs were separated from the mixed hepatocytes, and purified by rapid adherent characteristics. Finally, the production and activity of KCs obtained by this modified method were compared with those isolated by Percoll density gradient centrifugation. We used F4/80 antibody immunofluorescence technique to observe morphological features of KCs, flow cytometry (FCM) to detect the expression of F4/80 antibody and the ink uptake test to observe the phagocytic activity. Moreover, using FCM, we evaluated the expressions of molecules associated with antigen presentation, including major histocompatibility complex class II (MHC II), CD40, CD86 and CD68 on the surface of KCs subjected to hypoxia/reoxygenation (H/R) modeling. And, ELISA was conducted to measure tumor necrosis factor-alpha (TNF-alpha) production of the cultured KCs following H/R. Results The yield of KCs was (5.83+/-0.54)*10(6) per mouse liver and the survival rate of KCs was up to 92% by low-speed centrifugation and rapid adherent method. Compared with Percoll density gradient centrifugation [the yield of KCs was (2.19+/-0.43)*10(6) per liver], this new method significantly improved the yield of KCs. F4/80 immunofluorescence showed typical morphologic features of KCs such as spindle or polygon shapes and FCM identified nearly 90% F4/80 positive cells. The phagocytic assay showed that lots of ink particles were phagocytosed into the isolated cells. KC H/R models expressed more MHC II, CD40 and CD86 and produced more TNF alpha participating in inflammation. Conclusion The efficient method to isolate and purify KCs from BALB /c mice has been successfully established. PMID- 27412930 TI - [Homology modeling and eukaryotic expression of a modified alphabeta TCR harboring the immunoglobulin-like domain of gammadelta TCR]. AB - Objective To design, construct and express a chimeric alphabeta TCR harboring the immunoglobulin-like (Ig) domain of gammadelta TCR in Jurkat T cells. Methods The fusion sites of TCR deltaIg were determined by bioinformatics analysis. Then the protein structures of TCR alpha deltaIg and TCR beta deltaIg were predicted by homology modeling. Furthermore, the structures of TCR alpha deltaIg and TCR beta deltaIg were compared with the wild type (wt) TCR alpha and TCR beta respectively by combinatorial extension (CE). After that, the TCR alpha deltaIg and TCR beta deltaIg were fused to fluorescent protein ECFP and EYFP respectively via the overlap PCR, and then the fusion genes (TCR alpha deltaIg-ECFP and TCR beta deltaIg-EYFP) were cloned into pIRES2-EGFP vector and respectively located at the upstream and downstream of an internal ribosome entry site (IRES). The recombinant prokaryotic expression vector pIRES-TCR betadeltaIg-EYFP/TCR alphadeltaIg-ECFP was transferred into Jurkat T cells. Finally, the expression of TCR deltaIg in Jurkat T cells was monitored by confocal laser scanning microscopy (CLSM). Results The variable region structure of the TCR deltaIg did not change and the antigen recognition active regions remained stable compared to the wtTCR. The recombinant expression plasmid was successfully constructed as confirmed by PCR identification and sequencing analysis. CLSM showed that TCR deltaIg was expressed and located at the plasma membrane of Jurkat T cells. Conclusion The design of TCR deltaIg was reasonable and the TCR deltaIg could be expressed on Jurkat T cell surface. PMID- 27412931 TI - [Intestinal dysbacteriosis promotes intestinal intraepithelial T lymphocyte activation and proinflammatory cytokine secretion in mice]. AB - Objective To study the effect of intestinal dysbacteriosis on mouse intestinal intraepithelial T lymphocytes (iIELs). Methods The intestinal dysbacteriosis was induced in mice by oral administration of ceftriaxone sodium. The iIELs were digested with ethylene diaminetetraacetic acid (EDTA) and DL-dithiothreitol (DTT). The phenotype of iIELs and the proportions of subsets of T cells were detected by flow cytometry; the concentrations of cytokines (IL-2, IL-6, IFN gamma) in the intestine were examined by ELISA; the intestinal bacteria were analyzed with selective medium and PCR. Results Compared with the control group, intestinal commensal bacteria in mice were significantly reduced after the administration of ceftriaxone sodium, but fungi and yeasts increased. The proportions of T cell subgroups in ilELs changed, in which the proportion of TCR gammadelta(+)T cells significantly increased, and the activated CD3(+)T, CD8(+)T and TCR gammadelta(+)T cells increased. The concentrations of IL-2, IL-6 and IFN gamma were significantly raised in the intestine. Conclusion The dysbacteriosis results in the decrease of commensal bacteria, the increase of the fungus, the damage of microbial barrier, the more activated T cells in ilELs and the promotion of proinflammatory cytokine secretion in the gut. This is probably one of the reasons for inflammatory bowel disease caused by dysbacteriosis. PMID- 27412932 TI - [The siRNA-mediated silencing of Bmi-1 promotes apoptosis and inhibits invasion of MCF-7 breast cancer cells]. AB - Objective To investigate the effect of small interfering RNA (siRNA)-mediated silencing of the Bmi-1 gene on cell proliferation and invasion of MCF-7 human mammary carcinoma cell line and the potential molecular mechanisms. Methods Real time quantitative PCR was used to detect the levels of Bmi-1 mRNA in the paired breast cancer and adjacent noncancerous breast tissues which were confirmed by pathological diagnosis. Bmi-1-siRNA was transfected into MCF-7 cells by a Lipofectamine(R) RNAiMAX transfection reagent. Flow cytometry was used to detect cell cycle and apoptosis of MCF-7 cells transfected by Bmi-1-siRNA. Western blotting was performed to detect the protein levels of P21, Bax and Bcl-2. Matrigel Transwell(TM) invasion assay was used to determine the cell invasion of MCF-7 cells with Bmi-1 silencing. The protein levels of E-cadherin, N-cadherin, vimentin were tested by Western blotting. Results The expression of Bmi-1 mRNA in the breast cancer tissues was higher than that in the adjacent noncancerous breast tissues. Bmi-1 silencing significantly suppressed the cell growth, arrested the cells in the G1/S phase and promoted the apoptosis of MCF-7 cells. Compared with blank control group or negative control group, the Bmi-1-silenced group showed the increased expressions of P21 and Bax and the decreased expression of Bcl-2. In addition, Bmi-1 silencing significantly suppressed the cell invasion and promoted the expression of E-cadherin as well as downregulated the expressions of N-cadherin and vimentin in MCF-7 cells. Conclusion The invasion of MCF-7 cells can be inhibited by Bmi-1 silencing, of which the molecular regulation mechanism might be associated with the inhibition of tumor cell epithelial-mesenchymal transition. PMID- 27412933 TI - [Therapeutical effect of growth-associated protein 43 (GAP43) gene-modified bone marrow mesenchymal stem cell transplantation on rat retinal degenerative diseases]. AB - Objective To investigate the potential of the treatment of growth-associated protein 43 (GAP43) gene-modified bone marrow-derived mesenchymal stem cells (BMSCs) for retinitis pigmentosa (RP). Methods BMSCs were isolated and cultured by adherence method. By transfecting GAP43 gene into BMSCs via a lentivirus vector, we got GAP43 gene-modified BMSCs. Sixty-three Royal College of Surgeons (RCS) rats were randomly divided into three groups: experimental group, negative control group and blank control group. The experimental rats received subretinal injection of GAP43 gene-modified BMSCs. The negative control rats received subretinal injection of BMSCs. The control rats received subretinal injection of PBS. Thirty days after transplanting, the retinal thickness was detected by optical coherence tomography (OCT), and the expression of rhodopsin in RCS rat retinas was examined by Western blotting. Results Compared with the blank control group and the negative control group, 30 days after GAP43 gene-modified BMSC transplantation, the retinal thickness of the experimental group remarkably increased and the expression of rhodopsin significantly rose. Conclusion GAP43 gene-modified BMSC transplantation can increase survival photoreceptor cells and delay retinal degeneration. PMID- 27412934 TI - [The modulation of low-level laser on polarization of mouse bone marrow-derived macrophages]. AB - Objective To investigate the influence of 810 nm low-level laser of different energy on the polarization of macrophages. Methods The macrophages were isolated from the bone borrow of BALB/c mice and cultured in macrophage colony stimulating factor (M-CSF) conditioned cultural medium. The expression of F4/80 was examined by flow cytometry for identification. After lipopolysaccharide-gamma interferon (LPS-IFN-gamma) induced polarization status in the macrophages, the mRNA expressions of inducible nitric oxide synthase (iNOS), arginase 1 (Arg1) and CD86 were detected by reverse transcription PCR, and the protein expressions of iNOS and Arg1 were tested by Western blotting. Thereafter, the M1 macrophages were exposed to 810 nm low-level laser of (1, 2, 3, 4) J/cm(2), and then the cell viability was evaluated by MTT assay; the expressions of iNOS and Arg1 were observed by immunofluorescent cytochemical staining; the mRNA and protein levels of iNOS and Arg1 were studied by reverse transcription PCR and Western blotting. Results Flow cytometry showed that the percentage of F4/80 positive cells cultured with M-CSF conditioned medium was 99.9%. The mRNA and protein levels of iNOS and CD86 in macrophages were both significantly raised after induction by LPS-IFN-gamma. Compared with the control cells, the viability of M1 cells significantly decreased when the energy of the low-level laser exposure was 4 J/cm(2), while the viability remained unchanged when the energy was 1, 2 or 3 J/cm(2). Immunocytochemistry revealed that the percentage of Arg1 positive cells that represent M2 macrophages was not significantly different from the control group when the irradiation dose was 1 or 2 J/cm(2), however, the Arg1 positive cells significantly increased and the iNOS positive cells that represent M1 macrophages significantly decreased when the irradiation dose was 3 or 4 J/cm(2). When the irradiation dose was 1 or 2 J/cm(2), the mRNA and protein levels of iNOS and Arg1 remained unchanged compared with the control group. When the irradiation dose was 3 or 4 J/cm(2), the mRNA and protein levels of iNOS significantly decreased and Arg1 significantly increased. Conclusion The 810 nm low-level laser with the energy of 1 or 2 J/cm(2) have no significant influence on the polarization and viability of macrophages. M1 macrophages can be polarized into M2 macrophages while there is no significant difference in the cell viability when the energy was 3 J/cm(2). When the energy was 4 J/cm(2), M1 cells can be polarized into M2 cells and the cell viability significantly decreased. PMID- 27412935 TI - [Downregulation of miR-18a or miR-328 inhibits the invasion and migration of lung adenocarcinoma A549 cells]. AB - Objective To investigate the expressions of miR-18a and miR-328 in lung adenocarcinoma A549 cells, and explore the effect of miR-18a or miR-328 on invasion and migration of A549 cells. Methods The expressions of miR-18a and miR 328 in A549 cells were detected by real-time quantitative PCR. Then the specific miR-18a or miR-328 inhibitor sequences were transfected into A549 cells to downregulate the expression of miR-18a or miR-328. The invasion and migration abilities of A549 cells were evaluated by Transwell(TM) assay. Results The miR 18a and miR-328 were overexpressed in A549 cells. And with the corresponding inhibitors being transfected, the expressions of miR-18a and miR-328 in A549 cells were downregulated. In addition, TranswellTM assay showed that decreased expression of miR-18a or miR-328 significantly inhibited the invasion and migration of A549 cells. Conclusion Downregulation of miR-18a or miR-328 can inhibit the invasion and migration abilities of A549 cells effectively. PMID- 27412936 TI - [Selectively activating melanocortin 4 receptor acts against rat sepsis-induced acute liver injury via HMGB1/TLR4/NF-kappaB signaling pathway]. AB - Objective To observe the effect of selective activation of melanocortin 4 receptor (MC4R) on the rats with sepsis-induced acute liver injury. Methods Sixty four male SD rats were randomly grouped into sham operation group (PBS treatment after sham operation), cecal ligation and puncture (CLP) group (sepsis model was established by CLP), Ro27-3225 treatment group (Ro27-3225 treatment after CLP), and Ro27-3225 sham operation control group (Ro27-3225 treatment after sham operation), 16 rats for each group (ten rats were used to observe general condition and 72-hour survival after operation. Then, six rats were used to collect blood and liver samples). These groups were intraperitoneally injected with PBS or Ro27-3225 (180 MUg/kg) 30 minutes after operation. Heart rate (HR), mean arterial pressure (MAP), aspartate transaminase (AST) and alanine transaminase (ALT) were measured 24 hours after operation. After execution of the rats, pathological changes of liver tissues were observed by HE staining. The levels of Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1) and caspase-3 mRNA in liver tissues were analyzed by reverse transcription PCR. The expression of nuclear factor-kappaB (NF-kappaB) p65 in hepatocytes was detected by immunohistochemical staining, which was followed by analysis of nuclear positive rate of NF-kappaB p65. Results Compared with the sham operation group, CLP group showed decreased 72-hour survival and MAP, significantly increased levels of AST and ALT, hepatic cords disorder, hepatocyte swelling, and diffuse inflammatory cell infiltration; the levels of TLR4, HMGB1 and caspase-3 mRNA in liver tissues remarkably increased, and the positive rate of NF-kappaB p65 in hepatocytes went up as well. However, compared with the CLP group, the Ro27-3225 treatment group was found with obviously increased 72-hour survival and MAP, inhibited levels of AST and ALT, attenuated damage of liver tissues, decreased levels of TLR4, HMGB1 and caspase-3 mRNA in liver tissues, and significantly downregulated positive rate of NF-kappaB p65 in hepatocytes. Conclusion Sepsis causes liver injury. Selectively activating MC4R can reduce sepsis-induced acute liver injury in rats, which may act via inhibiting HMGB1/TLR4/NF-kappaB signaling pathway to relieve inflammation response. PMID- 27412937 TI - [Mechanism of losartan suppressing vascular calcification in rat aortic artery]. AB - Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process. PMID- 27412938 TI - [Relationship between PTEN mutations and protein kinase B phosphorylation caused by insulin or recombinant human epidermal growth factor stimulation]. AB - Objective To study the effect of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mutations on protein kinase B (Akt) phosphorylation of CNE-1 nasopharyngeal carcinoma cell line. Methods CNE-1 cells were cultured in RPMI1640 medium containing 100 mL/L fetal calf serum, and then transfected with wild-type PTEN (wtPTEN), mutant PTEN C124S and mutant PTEN G129E plasmid separately. After overnight serum starvation, the cells were stimulated with 0.15 IU/mL insulin or 0.3 MUg/mL recombinant human epidermal growth factor (rhEGF). At last, Akt phosphorylation was evaluated by Western blotting. Results Insulin or rhEGF stimulation led to Akt activation in CNE-1 cells. The wtPTEN inhibited insulin- or rhEGF-stimulated phosphorylation of Akt. PTEN C124S mutant activated insulin stimulated phosphorylation of Akt, but not rhEGF-stimulated phosphorylation of Akt. PTEN G129E mutant inhibited insulin-stimulated phosphorylation of Akt. Conclusion The wtPTEN inhibited insulin- or rhEGF-stimulated phosphorylation of Akt, while PTEN C124S and G129E mutants failed to activate the phosphorylation of Akt consistently. This suggested PTEN mutations might not be correlated with activated Akt. PMID- 27412940 TI - [Over-expression of miR-141 inhibits the proliferation, invasion and migration of hepatocellular carcinoma MHCC-97H cells]. AB - Objective To observe the expression level of miR-141 in tumor tissues of human hepatocellular carcinoma (HCC) and determine the effect of miR-141 level on cell proliferation, invasion and migration of MHCC-97H cells by upregulation of miR 141. Methods We checked the miR-141 expression level in HCC by real-time quantitative PCR and analyzed the relationship between the expression level of miR-141 and clinical pathological indicators as well as survival rate. MHCC-97H cells were transiently transfected with miR-141 mimics which were artificially synthesized. The proliferation of MHCC-97H cells was detected by MTT assay. Transwell(TM) assay was performed to examine the invasion and migration of MHCC 97H cells. The expression of erythropoietin-producing hepatocellular receptor A2 (EphA2), which was the potential downstream target, was determined by Western blotting and immunohistochemistry. Results The expression level of miR-141 in HCC tissues was significantly lower than that in the adjacent normal tissues, and it was obviously associated with TNM stage, portal vein infiltration and Edmondson degree. Patients in the lower miR-141 group had a worse 3-year survival than those in higher miR-141 group. Overexpression of miR-141 in MHCC-97H cells significantly suppressed cell proliferation, invasion and migration, and inhibited the protein expression of EphA2. Correlation analysis showed that miR 141 level was negatively correlated with EphA2 expression level. Conclusion miR 141 is down-regulated in HCC tissues and it is negatively correlated with EphA2 expression. Its low expression is correlated with the malignant clinical pathological features. miR-141 overexpression down-regulates EphA2 expression and subsequently inhibits the proliferation, invasion and migration of HCC cells. PMID- 27412939 TI - [Shengqifuzheng Injection promotes the recovery of B cells in gut-associated lymphoid tissues of mice treated with cyclophosphamide]. AB - Objective To investigate the effect of Shengqifuzheng Injection (SQFZ) on the number recovery of B cells in gut-associated lymphoid tissues (GALTs) of mice receiving cyclophosphamide-based chemotherapy. Methods BALB/c mice were randomly divided into control group, cyclophosphamide (Cy) group and SQFZ group. Mice in Cy group and SQFZ group were injected intraperitoneally with Cy (100 mg/kg), while the control mice were injected with an equal volume of normal saline. Twenty-four hours later, mice in SQFZ group were administrated intragastricly with 1 mL SQFZ once daily for 10 consecutive days, and mice in the other groups were given the same volume of normal saline. Body mass of all the mice was measured every day. Mice were killed on day 10, and the indexes of spleen and thymus were measured. Cell cycles of bone marrow cells and the percentage of B cells in lymphocytes in mesenteric lymph node (MLN) and Peyer's patch (PP) were detected by flow cytometry. In vitro, after being treated with SQFZ, activity of lymphocytes was evaluzed by MTT assay; expression of CD86 on B cell surface was analyzed by flow cytometry; and B cell proliferation was tested by carboxyfluorescein succinimidyl ester (CFSE)-based lymphocyte proliferation assay. Results SQFZ alleviated the loss of body mass caused by Cy and promoted the recovery of thymus indexes, spleen indexes and B cell number in MLN and PP. But it did not alleviate the bone marrow suppression of mice in this condition. In vitro, SQFZ enhanced lymphocyte activity, and improved the activation and proliferation of B cells. Conclusion SQFZ could accelerate the recovery of B cells in GALTs of mice receiving chemotherapy and it might act by promoting B cell proliferation. PMID- 27412941 TI - [The down-regulation of miR-125b-5p and up-regulation of Smad4 expression in human umbilical vein endothelial cells treated with hydrogen peroxide]. AB - Objective To explore the expressions and functions of miR-155, miR-125b-5p, miR 210, and their target proteins, in vascular endothelial cells in oxidative stress. Methods Human umbilical vein endothelial cells (HUVECs) were isolated and cultured; the expression of endothelial cell factor VIII related antigen was detected by immunofluorescence staining; and the expression of CD31 was detected and identified by flow cytometry. The oxidative stress model of vascular endothelial cells was established by preeclampsia serum and hydrogen peroxide (H2O2) treatment. The treated HUVECs were divided into 4 groups: normal pregnancy serum group, preeclampsia serum group, 0 MUmol/L H2O2 group and 100 MUmol/L H2O2 group. The levels of miR-155, miR-125b-5p, and miR-210 were tested by real-time quantitative PCR within 24 hours after modeling. The expression of Smad4 protein was detected by Western blotting and immunofluorescence staining. Cell apoptosis was detected by flow cytometry combined with annexin V-FITC/PI staining. Results Compared with 0 MUmol/L H2O2 group, miR-125b-5p significantly decreased in 100 MUmol/L H2O2 group, while Smad4 protein significantly increased. In addition, 100 MUmol/L H2O2 treatment promoted cell apoptosis and necrosis. Compared with normal pregnancy serum group, the apoptosis and necrosis were significantly enhanced in preeclampsia serum group, but there were no significant differences in miR-125b 5p and Smad4 between the groups. Conclusion High level of H2O2 up-regulates Smad4 protein expression and inhibits miR-125b-5p expression. PMID- 27412942 TI - [Xinfeng capsule improves hypercoagulative state by inhibiting miR-155/NF-kappaB signaling pathway in patients with active ankylosing spondylitis]. AB - Objective To observe the effect of Xinfeng capsule (XFC) on miR-155, nuclear factor kappa B (NF-kappaB) signal pathway, and indexes related to hypercoagulative state in patients with active ankylosing spondylitis (AS), and investigate the possible mechanism. Methods Fifty-six cases in active AS were randomly divided into XFC group and sulfasalazine (SASP) group. All cases in the XFC group took three capsules three times daily for twelve consecutive weeks. The ones in the SASP group took four tablets two times daily for twelve consecutive weeks. The expression of miR-155 was detected by real-time PCR. The mRNA expressions of nuclear factor kappaB activator 1(Act1), NF-kappaB inhibitor-alpha (IkappaBalpha), inhibitor of kappa-B kinase beta (IKKbeta), NF-kappaB p65, and NF kappaB p50 were tested by reverse transcription PCR (RT-PCR). Meanwhile, the protein expressions of NF-kappaB P65 and NF-kappaB P50 were determined by Western blotting. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-10, IL 17, thromboxane B2 (TXB2), 6-ketone-prostaglandin F1 (6-keto-PGF1), platelet granular membrane protein 140 (GMP140), platelet activation factor (PAF), and plasminogen activator inhibitor-2 (PAI-2) were determined by ELISA. Clinical efficacy was evaluated in the two groups. Results Compared with the SASP group, 50% Bath ankylosing spondylitis disease activity index (BASDAI50) was significantly higher in the XFC group. Compared with the SASP group after treatment, platelet (PLT), fibrinogen (FBG) and D-D dimer (D-D), TXB2, GMP140, PAF, PAI-2, IL-17, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analog scale (VAS), BASDAI, BASFI, and BAS-G were reduced more obviously in the XFC group after treatment; meanwhile, 6-keto-PGF1, IL-4, and IL 10 significantly increased. Compared with the SASP group after treatment, the expressions of IKKbeta mRNA, IkappaBalpha mRNA, NF-kappaB p65 mRNA, NF-kappaB p50 mRNA, NF-kappaB P65 protein, NF-kappaB P50 protein, and miR-155 were lower in the XFC group after treatment. Conclusion XFC could effectively improve hypercoagulative state in active AS patients. The potential mechanism may be associated with the inhibition of miR-155 and NF-kappaB signal pathway. PMID- 27412943 TI - [Association between cytotoxic T lymphocyte protein-4 polymorphisms and non Hodgkin's lymphoma risk: a meta-analysis]. AB - Objective To investigate the potential association of cytotoxic T lymphocyte associated protein 4 (CTLA4) polymorphisms with non-Hodgkin's lymphoma (NHL) risk. Methods Two reviewers independently searched the PubMed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese WanFang databases and Database of Chinese Scientific and Technical Periodicals (VIP) for relevant studies from January 1, 1990 to May 25, 2016. Odds ratios (OR) with 95% confidence intervals (CI) for CTLA4 polymorphism and HNL risk were used to evaluate the strength of association. Meta-analysis was performed using SATA (v12.0) software. Results A total of 6 case-control studies concerning the CTLA4 +49A/G, -318T/C, and CT60A/G polymorphisms were included in the meta-analysis. The polymorphisms of the three alleles were not associated with genetic susceptibility to NHL (PZ>0.05 or 95%CI contains 1). In the subgroup analysis of CTLA4 +49A/G gene polymorphism, we found that AA was a risk factor for mixed type lymphoma (AA vs GG: OR=4.181, 95%CI: 1.362-12.833; AA+AG vs GG: OR=3.217, 95%CI: 1.055-9.810; AA vs AG+GG: OR=2.827, 95%CI: 1.345-5.940), but was a protect factor for B cell lymphoma (AA vs GG: OR=0.465, 95%CI: 0.251-0.863; AA vs AG+GG: OR=0.534, 95%CI: 0.362-0.788); AA was a risk factor in Italians (AA vs GG: OR=4.181, 95%CI: 1.362-12.833; AA+AG vs GG: OR=3.217, 95%CI: 1.055-9.810; AA vs AG+GG: OR=2.827, 95%CI: 1.345-5.940), but was a protect factor in Chinese (AA vs GG: OR=0.643, 95%CI: 0.417-0.992; AA vs AG+GG, OR=0.601, 95%CI: 0.395-0.913). Conclusion This meta-analysis suggests that the polymorphisms of the three alleles are not associated with genetic susceptibility to NHL. PMID- 27412944 TI - [Correlation between the genetic polymorphisms of apolipoprotein M with the susceptibility to rheumatic diseases of Chinese Han populastion in Lanzhou]. AB - Objective To investigate the relationship between the genetic polymorphisms of apolipoprotein M (ApoM) and the susceptibility to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) among Chinese Han population in Lanzhou. Methods Primers for the two single nucleotide polymorphism (SNP) sites (rs805296 and rs805297) in ApoM gene were designed and their genotyping methods of polymerase chain reaction-high resolution melting (PCR-HRM) assay were established. Case-control studies were performed among the 599 cases of RA, 194 cases of SLE, 179 cases of AS and 273 matched healthy controls to analyze the correlations between the two SNPs and the susceptibility to rheumatic diseases. Results The genotype frequencies of rs805296 were AA 87.0%, AG 12.7%, GG 0.3% in RA cases, AA 84.5%, AG 15.0%, GG 0.5% in SLE cases, AA 91.6%, AG 7.3%, GG 1.1% in AS cases, AA 85.0%, AG 15.0%, GG 0% in healthy controls. The ones of rs805297 were GG 38.2%, GT 51.8%, TT 10.0% in RA cases, GG 44.3%, GT 45.4%, TT 10.3% in SLE cases, GG 37.4%, GT 47.5%, TT 15.1% in AS cases, GG 40.7%, GT 46.1%, TT 13.2% in healthy controls. Statistical analyses showed that only the genotype distribution of rs805296 was significantly different between the AS cases and the healthy controls. Under the dominant model, the G allele carriers of rs805296 (AG heterozygote and GG homozygote) were found to significantly decrease the risk for AS development. Conclusion The established PCR-HRM genotyping assays in the present study can successfully achieve the molecular diagnosis of the two SNPs sites (rs805296 and rs805297) from clinical samples, and the study found a significant association between the SNP of rs805296 and the susceptibility to AS among Chinese Han population in Lanzhou. PMID- 27412945 TI - [Preparation of monoclonal antibodies against enterovirus type 71 with an epitope incorporated adenovirus type 3 vector]. AB - Objective To develop the monoclonal antibodies (mAbs) against enterovirus type 71 (EV71). Methods Two neutralization epitopes, SP70 and SP55, from EV71 were cloned into the hexon gene of adenovirus type 3 to generate a recombinant adenovirus type 3 (R1R2A3) presenting SP70 and SP55 antigens. BALB/c mice were immunized with the R1R2A3. The mAbs were developed with hybridoma technology and were analyzed with microneutralizing assay, indirect ELISA, Western blotting and direct immunofluorescence assay (DFA). Results The study obtained four hybridoma cell clones, 2C4, D2C9, I2G2 and I12C3. ELISA showed that the titer of D2C9 against EV71 was 1:8 000 000 and the titers of 2C4, I2G2, and I12C3 all were 1:500 000. ELISA and Western blotting demonstrated that all mAbs could specifically recognize the VP1 of EV71. In addition, D2C9 recognized the SP70 epitope, and 2C4, I12C3 and I2G2 all recognized the SP55 epitope. DFA revealed that all mAbs could react with EV71, but not with Coxsackie virus A16 (CoxA16). Conclusion Four mAbs against EV71 have been developed successfully, and all of them could react with EV71 rather than CoxA16. PMID- 27412946 TI - Beneficial Effect of Endovascular Therapy and Low-Density Lipoprotein Apheresis Combined Treatment in Hemodialysis Patients With Critical Limb Ischemia due to Below-Knee Arterial Lesions. AB - To assess the clinical benefit of combined treatment of below-knee endovascular therapy (BK-EVT) plus low-density lipoprotein apheresis (LDLA) compared with BK EVT monotherapy, we retrospectively evaluated the clinical outcome of hemodialysis (HD) patients with critical limb ischemia (CLI) due to isolated BK arterial lesions who underwent BK-EVT or BK-EVT plus short-term LDLA. Between October 2011 and September 2014, 62 HD patients underwent isolated BK-EVT monotherapy (BK-EVT group), and 25 HD patients underwent BK-EVT plus LDLA (BK-EVT + LDLA group). LDLA was started within 1 week after BK-EVT and performed four times in total within next 2 weeks. Major adverse limb events (MALE) including major amputation and re-intervention, and all-cause mortality were examined by Kaplan-Meier method and the log-rank test. Baseline characteristics were not different other than low ABI and low dorsal SPP in BK-EVT + LDLA group. Cumulative MALE-free rate was significantly improved in BK-EVT + LDLA group over the BK-EVT group (72.0% and 45.1% respectively at 30 months after treatment, P = 0.04). All-cause mortality did not differ between the two groups. Major causes of death were heart failure and sepsis in both groups. Short-term LDLA hybrid treatment immediately after BK-EVT might improve the outcome of ischemic limbs after re-vascularization therapy. PMID- 27412947 TI - Impact of Precooling and Controlled-Atmosphere Storage on gamma-Aminobutyric Acid (GABA) Accumulation in Longan (Dimocarpus longan Lour.) Fruit. AB - Longan (Dimocarpus longan Lour.) fruit cultivars 'Chuliang' and 'Shixia' were analyzed for gamma-aminobutyric acid (GABA) accumulation after precooling and in controlled-atmosphere storage. Fruit were exposed to 5% O2 plus 3%, 5%, or 10% CO2 at 4 degrees C, and GABA and associated enzymes, aril firmness, and pericarp color were measured. Aril softening and pericarp browning were delayed by 5% CO2 + 5% O2. GABA concentrations and glutamate decarboxylase (GAD; EC 4.1.1.15) activities declined during storage at the higher-CO2 treatments. However, GABA aminotransferase (GABA-T; EC 2.6.1.19) activities in elevated CO2-treated fruit fluctuated during storage. GABA concentrations increased after precooling treatments. GAD activity and GABA-T activity were different between cultivars after precooling. GABA concentrations in fruit increased after 3 days of 10% CO2 + 5% O2 treatment and then declined as storage time increased. GABA accumulation was associated with stimulation of GAD activity rather than inhibition of GABA-T activity. PMID- 27412948 TI - The validated sun exposure questionnaire: association of objective and subjective measures of sun exposure in a Danish population-based sample. AB - BACKGROUND: Few questionnaires used in monitoring sun-related behaviour have been tested for validity. OBJECTIVES: We established the criteria validity of a questionnaire developed for monitoring population sun-related behaviour. METHODS: During May-August 2013, 664 Danes wore a personal electronic ultraviolet radiation (UVR) dosimeter for 1 week that measured their outdoor time and dose of erythemal UVR exposure. In the following week, they answered a questionnaire on their sun-related behaviour in the measurement week. RESULTS: Outdoor time measured by dosimetry correlated strongly with both outdoor time and the developed exposure scale measured in the questionnaire. Exposure measured in standard erythema dose (SED) by dosimetry correlated strongly with the exposure scale. In a linear regression model of UVR (SED) received, 41% of the variation was explained by skin type, age, week of participation and exposure scale, with exposure scale as the main contributor. The weekly sunburn fraction correlated strongly with the number of ambient sun hours (r = 0.73, P < 0.001). CONCLUSIONS: This criteria-validated questionnaire provides evidence of the exposure that the questionnaire aimed to measure. The evidence provided showed a strong link between the objectively measured behaviour and the behaviour measured by this survey construct. The questionnaire is the first validated tool to measure the UVR exposure in a national population-based sample. PMID- 27412949 TI - Taking Brief Strategic Family Therapy from Bench to Trench: Evidence Generation Across Translational Phases. AB - In this article, we review the research evidence generated over 40 years on Brief Strategic Family Therapy illustrating the NIH stages of intervention development and highlighting the translational process. Basic research (Stage 0) led to the discovery of the characteristics of the population and the nature of the problems that needed to be addressed. This step informed the selection of an intervention model that addressed the problems presented by the population, but in a fashion that was congruent with the population's culture, defined in terms of its value orientations. From this basic research, an intervention that integrated structural and strategic elements was selected and refined through testing (Stage I). The second stage of translation (Stage II) included efficacy trials of a specialized engagement module that responded to challenges to the provision of services. It also included several other efficacy trials that documented the effects of the intervention, mostly in research settings or with research therapists. Stages III/IV in the translational process led to the testing of the effectiveness of the intervention in real-world settings with community therapists and some oversight from the developer. This work revealed that an implementation/organizational intervention was required to achieve fidelity and sustainability of the intervention in real-world settings. The work is currently in Stage V in which new model development led to an implementation intervention that can ensure fidelity and sustainability. Future research will evaluate the effectiveness of the current implementation model in increasing adoption, fidelity, and long-term sustainability in real-world settings. PMID- 27412950 TI - Age-related reduction of chromatin fractal dimension in toluidine blue - stained hepatocytes. AB - In this study, we proposed a hypothesis that chromatin of mouse hepatocytes exhibits age-related reduction of fractal dimension. This hypothesis was based on previously published works demonstrating that complexity of biological systems such as tissues, decreases during the process of physiological aging. Liver tissue was obtained from 24 male mice divided into 3 age groups: 10-days-old (young, juvenile), 210-days-old (adult) and 390-days-old. The tissue was stained using a modification of toluidine blue (nucleic acid - specific) staining method. A total of 480 chromatin structures (20 for each animal) were analyzed. For each structure, the values of fractal dimension, lacunarity, textural angular second moment and inverse difference moment were calculated using ImageJ software and its plugins. The results indicated the age-related reduction in fractal dimension and increase in lacunarity (p<0.01). Fractal dimension is a potentially good indicator of age associated changes in chromatin structure. To our knowledge, this is the first study to show that fractal complexity of hepatocyte chromatin decreases during the process of physiological aging. Fractal analysis as a method could be useful in detection of small age-related changes in chromatin distribution not otherwise visible with naked eye on conventional tissue micrographs. PMID- 27412951 TI - G-protein-coupled receptor kinase 2 terminates G-protein-coupled receptor function in steroid hormone 20-hydroxyecdysone signaling. AB - G-protein-coupled receptors (GPCRs) transmit extracellular signals across the cell membrane. GPCR kinases (GRKs) desensitize GPCR signals in the cell membrane. However, the role and mechanism of GRKs in the desensitization of steroid hormone signaling are unclear. In this study, we propose that GRK2 is phosphorylated by protein kinase C (PKC) in response to induction by the steroid hormone 20 hydroxyecdysone (20E), which determines its translocation to the cell membrane of the lepidopteran Helicoverpa armigera. GRK2 protein expression is increased during the metamorphic stage because of induction by 20E. Knockdown of GRK2 in larvae causes accelerated pupation, an increase in 20E-response gene expression, and advanced apoptosis and metamorphosis. 20E induces translocation of GRK2 from the cytoplasm to the cell membrane via steroid hormone ecdysone-responsive GPCR (ErGPCR-2). GRK2 is phosphorylated by PKC on serine 680 after induction by 20E, which leads to the translocation of GRK2 to the cell membrane. GRK2 interacts with ErGPCR-2. These data indicate that GRK2 terminates the ErGPCR-2 function in 20E signaling in the cell membrane by a negative feedback mechanism. PMID- 27412952 TI - The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. AB - BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype phenotype correlates and performed survival analysis to identify prognostic factors. RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. CONCLUSIONS: The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date. PMID- 27412953 TI - Novel myosin-based therapies for congenital cardiac and skeletal myopathies. AB - The dysfunction in a number of inherited cardiac and skeletal myopathies is primarily due to an altered ability of myofilaments to generate force and motion. Despite this crucial knowledge, there are, currently, no effective therapeutic interventions for these diseases. In this short review, we discuss recent findings giving strong evidence that genetically or pharmacologically modulating one of the myofilament proteins, myosin, could alleviate the muscle pathology. This should constitute a research and clinical priority. PMID- 27412954 TI - High HIV incidence in men who have sex with men attending for postexposure prophylaxis: a service evaluation. AB - BACKGROUND/AIMS: There are limited outcome data for men who have sex with men (MSM) who have received HIV postexposure prophylaxis (PEP). The objective of this service evaluation was to determine HIV incidence and repeat PEP use among MSM PEP recipients in London, UK. METHODS: Retrospective electronic case-note review of all MSM who were prescribed PEP between January and April 2013 at a central London sexual health service. RESULTS: 530 MSM received PEP between 1 January and 30 June 2013. Of these, 449 had more than 30 days subsequent follow-up at our service. Median age was 31 years. PEP indication was unprotected anal intercourse, 98% (receptive 88% and insertive 10%) and other, 2%. Up to 1 November 2015, total follow-up was 756 person-years. 183 users received repeat PEP. The total number of repeat PEP courses was 442. 57 MSM newly acquired HIV: the HIV incidence was 7.6 per 100 person-years. CONCLUSIONS: PEP was associated with a high risk of subsequent HIV seroconversion in this cohort; this group may be appropriate candidates for pre-exposure prophylaxis. PMID- 27412956 TI - Treat signs of sepsis with same urgency as chest pain, says NICE. PMID- 27412955 TI - Formononetin exhibits anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice. AB - The aim of this study was to investigate the anti-hyperglycemic activity and mechanism of formononetin in alloxan-induced type 1 diabetic mice by determining its effect on some diabetes-related indices as described below. Body weight, fasting blood glucose, hepatic glycogen, serum insulin, and serum glucagon were determined by electronic scales, glucometer, and ELISA kits. Fas, Caspase-3, pancreatic and duodenal homeobox-1 , insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase and glucose-6-phosphatase mRNA, and proteins levels in liver tissue were detected by fluorogenic quantitative-polymerase chain reaction and Western blot assays. The results indicated that formononetin (5, 10, and 20 mg/kg; oral administration) reversed the alloxan-induced increase of some indices (fasting blood glucose level and Fas and Caspase-3 mRNA and proteins levels in pancreas tissue) and reduction of some indices (body weight gain, oral glucose tolerance, insulin activity, hepatic glycogen level, pancreatic and duodenal homeobox-1, insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase mRNA and protein levels in liver tissue). The glucagon level and glucose-6-phosphatase mRNA and protein levels in liver tissue were not affected by the drugs administration. In conclusion, formononetin exhibited anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice by inhibiting islet B cell apoptosis and promoting islet B cell regeneration, insulin secretion, hepatic glycogen synthesis, and hepatic glycolysis. PMID- 27412957 TI - Portomesenteric venous gas and pneumatosis intestinalis secondary to mesenteric ischaemia. PMID- 27412958 TI - Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway. AB - Annexin A1 (ANXA1) is a Ca(2+)-binding protein over-expressed in pancreatic cancer (PC). We recently reported that extracellular ANXA1 mediates PC cell motility acting on Formyl Peptide Receptors (FPRs). Here, we describe other mechanisms by which intracellular ANXA1 could mediate PC progression. We obtained ANXA1 Knock-Out (KO) MIA PaCa-2 cells using the CRISPR/Cas9 genome editing technology. LC-MS/MS analysis showed altered expression of several proteins involved in cytoskeletal organization. As a result, ANXA1 KO MIA PaCa-2 partially lost their migratory and invasive capabilities with a mechanism that appeared independent of FPRs. The acquisition of a less aggressive phenotype has been further investigated in vivo. Wild type (WT), PGS (scrambled) and ANXA1 KO MIA PaCa-2 cells were engrafted orthotopically in SCID mice. No differences were found about PC primary mass, conversely liver metastatization appeared particularly reduced in ANXA1 KO MIA PaCa-2 engrafted mice. In summary, we show that intracellular ANXA1 is able to preserve the cytoskeleton integrity and to maintain a malignant phenotype in vitro. The protein has a relevant role in the metastatization process in vivo, as such it appears attractive and suitable as prognostic and therapeutic marker in PC progression. PMID- 27412960 TI - A comprehensive insight of novel antioxidant therapies for atrial fibrillation management. AB - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF tends to self-perpetuate, due to structural and electrical remodeling in the atria. Currently, therapies for AF, such as, antiarrhythmic drugs and catheter ablation, have significant limitations. Antiarrhythmic drugs target one or a few cardiomyocyte ion channels and have considerable pro-arrhythmic and non-cardiac adverse effects. On the other hand, catheter ablation is an expensive treatment associated with measurable complications and its long-term success in management of AF is controversial. Current consensus guidelines recommend beta-blockers, amiodarone, digitalis glycosides and non-dihydropyridine calcium channel antagonists or a combination of them for AF treatment, but bradycardia and heart block may occur as an unwanted effect. On the other hand, antioxidant agents have recently attracted much interest in AF treatment because they have been associated with a reduction in lone AF and post-operative AF, and in some cases, with a decrease in long-term hospitalization time. Moreover, antioxidants can be considered a cheap treatment with reduced side effects. In this review, we will comprehensively review the effects and the mechanisms of action of several antioxidant agents, such as vitamin E, ascorbic acid, carotenoids, statins, omega 3 polyunsaturated fatty acids and N-acetylcysteine. PMID- 27412959 TI - Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders. AB - Major depressive disorder (MDD) and other mood disorders remain difficult to effectively treat, and innovative interventions and therapeutic targets are needed. Psychological stressors and inappropriate inflammation increase the risk and severity of mood disorders; however, only recently have the importance of sterile inflammatory processes in this effect been revealed. This review will introduce the reader to pathogen vs sterile inflammation, inflammatory receptor ligand interactions, microbial-associated molecular patterns (MAMPs), pathogen associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and the more recent discovery of the role of the inflammasome in peripheral and central nervous system cytokine/chemokine inflammatory responses. The review will focus on current preclinical and clinical evidence that sterile inflammation and inflammasome-dependent signaling may contribute to mood disorders. By understanding these inflammatory signaling processes, new approaches for quieting chronic or inappropriate inflammatory states may be revealed and this could serve as novel pharmacological targets for the treatment of mood disorders. PMID- 27412961 TI - Structure of purotoxin-2 from wolf spider: modular design and membrane-assisted mode of action in arachnid toxins. AB - Traditionally, arachnid venoms are known to contain two particularly important groups of peptide toxins. One is disulfide-rich neurotoxins with a predominance of beta-structure that specifically target protein receptors in neurons or muscle cells. The other is linear cationic cytotoxins that form amphiphilic alpha helices and exhibit rather non-specific membrane-damaging activity. In the present paper, we describe the first 3D structure of a modular arachnid toxin, purotoxin-2 (PT2) from the wolf spider Alopecosa marikovskyi (Lycosidae), studied by NMR spectroscopy. PT2 is composed of an N-terminal inhibitor cystine knot (ICK, or knottin) beta-structural domain and a C-terminal linear cationic domain. In aqueous solution, the C-terminal fragment is hyper-flexible, whereas the knottin domain is very rigid. In membrane-mimicking environment, the C-terminal domain assumes a stable amphipathic alpha-helix. This helix effectively tethers the toxin to membranes and serves as a membrane-access and membrane-anchoring device. Sequence analysis reveals that the knottin + alpha-helix architecture is quite widespread among arachnid toxins, and PT2 is therefore the founding member of a large family of polypeptides with similar structure motifs. Toxins from this family target different membrane receptors such as P2X in the case of PT2 and calcium channels, but their mechanism of action through membrane access may be strikingly similar. PMID- 27412962 TI - Radiographic Assessment of a Medullary Total Ankle Prosthesis: A Test of Agreement and Reliability. AB - : Total ankle replacement (TAR) is a viable alternative to ankle fusion in certain patients with end-stage ankle arthritis. Despite the importance of understanding alignment and movement of the prosthesis, there is no standardized radiographic method for evaluating the position and movement of the INBONE 2 prosthesis. The aims of this study were to describe a radiographic measurement protocol for INBONE 2 for clinical practice and research while determining the interobserver and intraobserver reliability using standard weightbearing radiographs. Fifteen patients were randomly selected with operative dates from January 2011 to January 2014 who underwent primary TAR using the INBONE 2 prosthesis. Most recent preoperative and first postoperative weightbearing anteroposterior and lateral radiographs were pulled and deidentified. Three foot and ankle surgeons blinded from the patient selection and deidentification, measured the described measurements on separate occasions. Intraobserver reliability: surgeon 1 had acceptable reliability for 9 of 13 continuous radiographic measurements (69.2%), surgeon 2 had acceptable reliability for 8 of 13 measurements (61.5%), and surgeon 3 had acceptable reliability for 12 of 13 measurements (92.3%). Interobserver reliability: among the first measurements, 6 of 13 continuous radiographic measurements (46.2%) had acceptable reliability. Among the second measurements, 7 of 13 measurements (53.8%) had acceptable reliability. Among the first and second measurements combined, 7 of 13 measurements (53.8%) had acceptable reliability. This study promotes the need for meticulous evaluation of annual radiographic findings following TAR in an effort to avoid catastrophic failure and represents moderate agreement can be obtained by employing the proposed measurements for surveillance of INBONE 2 TAR at annual postoperative visits. Measurements on the anteroposterior radiograph appear to demonstrate more consistent results for surveillance than lateral measurements. The intraobserver reliability results were somewhat superior to the interobserver reliability, implying more relevance for a single surgeon applying these measurements annually for postoperative surveillance. LEVELS OF EVIDENCE: Diagnostic, Level III. PMID- 27412965 TI - Patients with inflammatory bowel disease and their treating clinicians have different views regarding diet. AB - BACKGROUND: Diet and body composition play unclear roles in the pathogenesis, activity and symptoms of inflammatory bowel disease (IBD). Evidence-based guidance regarding dietary modification in IBD is lacking. We aimed to determine the attitudes of IBD patients and clinicians to diet. METHODS: The present cross sectional study comprised an online questionnaire distributed to members of a national IBD patient organisation, assessing demographics, anthropometry, disease phenotype and dietary beliefs. Dietitians, gastroenterologists and surgeons were targeted for a similar questionnaire as a result of membership of national professional bodies. RESULTS: Nine hundred and twenty-eight patients (72.2% female; mean age 39.5 years; age range 5-91 years) responded. Two-thirds of the patients had Crohn's disease. The mean reported body mass index was 24.9 kg m-2 and was significantly skewed to the right. Patients who had taken >10 courses of steroids were had a greater probability of being overweight or obese, independent of disease complications. Most patients (71%) assumed that their diet affected their IBD; 61% considered their IBD specialist disregarded the importance of diet. Of the 136 clinicians who responded, the majority felt that diet was a factor in symptoms and intestinal microbiota. More gastroenterologists (44%) than dietitians (17%) considered that diet had a role in the pathogenesis of IBD (P = 0.003). Twenty-six percent of patients reported receiving dietary advice from their IBD specialist, whereas 98% of gastroenterologists reported advice provision. Patients received diverse advice. Half of the patients followed recommendations provided by a clinician. CONCLUSIONS: The present study demonstrates that IBD patients consider diet to be important in their disease. IBD clinicians from different disciplines have diverse views of the role of diet. Advice given to patients is heterogeneous, often perceived as inadequate and poorly followed. PMID- 27412966 TI - Ax(H3O)2-xMn5(HPO3)6 (A = Li, Na, K and NH4): open-framework manganese(ii) phosphites templated by mixed cationic species. AB - Ax(H3O)2-xMn5(HPO3)6 (A = Li, x = 0.55 (1-Li); A = Na, x = 0.72 (2-Na); A = K, x = 0.30 (3-K); A = NH4, x = 0.59 (4-NH4)) phases were synthesized by employing mild hydrothermal conditions. 1-Li was studied by single crystal X-ray diffraction, while sodium, potassium and ammonium containing analogues were obtained as polycrystalline samples and characterized by powder X-ray diffraction. The four compounds were characterized by ICP-Q-MS, thermal analysis and XPS, IR, UV/Vis and EPR spectroscopy. Single crystal data indicate that 1-Li crystallizes in the P3[combining macron]c1 space group with lattice parameters a = 10.3764(1) A and c = 9.4017(1) A with Z = 2. The crystal structure of these phases is constituted by a three-dimensional [Mn(ii)5(HPO3)6](2-) anionic skeleton templated by alkali metal and ammonium cations together with protonated water molecules. Such an inorganic framework is formed by layers of edge-sharing MnO6 octahedra placed in the ab plane and joined along the c direction through phosphite pseudotetrahedra. The sheets display 12-membered ring channels parallel to the c-axis, ca. 5 A in diameter, where the extraframework species display a strong disorder. EPR measurements point to the existence of short range ferromagnetic interactions around 12 K. Magnetic susceptibility and heat capacity measurements show that all the compounds exhibit long range antiferromagnetic order below circa 4 K, with a significant magnetocaloric effect around the Neel temperature. PMID- 27412964 TI - The renal cortical collecting duct: a secreting epithelium? AB - KEY POINTS: The cortical collecting duct (CCD) plays an essential role in sodium homeostasis by fine-tuning the amount of sodium that is excreted in the urine. Ex vivo, the microperfused CCD reabsorbs sodium in the absence of lumen-to-bath concentration gradients. In the present study, we show that, in the presence of physiological lumen-to-bath concentration gradients, and in the absence of endocrine, paracrine and neural regulation, the mouse CCD secretes sodium, which represents a paradigm shift. This secretion occurs via the paracellular route, as well as a transcellular pathway that is energized by apical H+ /K+ -ATPase type 2 pumps operating as Na+ /K+ exchangers. The newly identified transcellular secretory pathway represents a physiological target for the regulation of sodium handling and for anti-hypertensive therapeutic agents. ABSTRACT: In vitro microperfusion experiments have demonstrated that cortical collecting ducts (CCDs) reabsorb sodium via principal and type B intercalated cells under sodium depleted conditions and thereby contribute to sodium and blood pressure homeostasis. However, these experiments were performed in the absence of the transepithelial ion concentration gradients that prevail in vivo and determine paracellular transport. The present study aimed to characterize Na+ , K+ and Cl- fluxes in the mouse CCD in the presence of physiological transepithelial concentration gradients. For this purpose, we combined in vitro measurements of ion fluxes across microperfused CCDs of sodium-depleted mice with the predictions of a mathematical model. When NaCl transport was inhibited in all cells, CCDs secreted Na+ and reabsorbed K+ ; Cl- transport was negligible. Removing inhibitors of type A and B intercalated cells increased Na+ secretion in wild type (WT) mice but not in H+ /K+ -ATPase type 2 (HKA2) knockout mice. Further inhibition of basolateral NaCl entry via the Na+ -K+ -2Cl- cotransporter in type A intercalated cells reduced Na+ secretion in WT mice to the levels observed in HKA2-/- mice. With no inhibitors, WT mouse CCDs still secreted Na+ and reabsorbed K+ . In vivo, HKA2-/- mice excreted less Na+ than WT mice after switching to a high-salt diet. Taken together, our results indicate that type A intercalated cells secrete Na+ via basolateral Na+ -K+ -2Cl- cotransporters in tandem with apical HKA2 pumps. They also suggest that the CCD can mediate overall Na+ secretion, and that its ability to reabsorb NaCl in vivo depends on the presence of acute regulatory factors. PMID- 27412969 TI - Behind neglected tropical deseases are... neglected people with diseases. PMID- 27412967 TI - Matrix metalloproteinase-1 induction by diethyldithiocarbamate is regulated via Akt and ERK/miR222/ETS-1 pathways in hepatic stellate cells. AB - Matrix metalloproteinase-1 (MMP-1) plays an important role in fibrolysis by degrading excessively deposited collagen I and III. We previously demonstrated that diethyldithiocarbamate (DDC) up-regulates MMP-1 in hepatic stellate cells via the ERK1/2 and Akt signalling pathways. In the current study, we attempted to further explore the molecular mechanisms involved in the regulation of MMP-1. We treated a co-cultured system that included hepatocytes (C3A) and hepatic stellate cells (LX-2) with DDC. The data revealed that the transcriptional factor ETS-1, which is an important regulator of MMP-1, was up-regulated in LX-2 cells following DDC treatment. Furthermore, the up-regulation of MMP-1 by DDC has been abrogated through employing si-ETS-1 to block expression of ETS-1. We found that DDC significantly inhibited the expression of miR-222 in LX-2 cells. We transfected miR-222 mimic into LX-2 cells and then co-cultured the cells with C3A. The up-regulation of ETS-1 and MMP-1 in LX-2 cells treated with DDC were inhibited after miR-222 mimic transfection. These data indicate that DDC up regulated MMP-1 in LX-2 cells through the miR-222/ETS-1 pathway. Finally, we treated the co-cultured system with an Akt inhibitor (T3830) and an ERK1/2 inhibitor (U0126). Both T3830 and U0126 blocked the suppression of miR-222 by DDC in LX-2. Collectively, these data indicate that DDC up-regulated MMP-1 in LX-2 cells through the Akt and ERK/miR-222/ETS-1 pathways. Our study provides experimental data that will aid the control of the process of fibrolysis in liver fibrosis prevention and treatment. PMID- 27412968 TI - Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours. AB - Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 <=2%, G2 3-20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required. PMID- 27412970 TI - Report from the 1st international workshop on oculocutaneous albinism in subsaharan Africa, Douala, Cameroon, July 24-25(th) 2015. PMID- 27412971 TI - History of health in the Indian Ocean: care, prevention, teaching, and research from the 17(th) to the mid-20th century. AB - In 1498, the Portuguese crossed the Cape of Good Hope. It was not until the period of 1633 and 1666, dates of the founding, respectively, of the Compagnie de l'Orient and the Compagnie des Indes orientales, that the way was definitively opened for trade between France and India. Because so many sailors developed scurvy after voyages that lasted 4 to 5 months, the French settled on Bourbon Island (Reunion) and Ile de France (Mauritius), to provide them with medical care. Created in 1689 by Louis XIV, the Navy Health Service was responsible for health in the colonies until it was replaced in 1890 by the Colonial Health Service. European medicine began its slow diffusion around the Indian Ocean in Pondicherry (India). The naval doctors reported their experiences in the Archives de medecine navale (1864-1889), and the colonial doctors afterwards in the Archives de medecine navale et coloniale (1890-1896). The health system in Madagascar developed strongly during 19(th) and 20(th) centuries, and the subsequent development of health care in the other Indian Ocean islands became closely linked to that of Madagascar. On Bourbon, the two navy hospitals in Saint Paul and Saint-Denis treated only naval and military personnel. The colony had no hospital providing care for civilians and poor people until three civilian doctors opened a maison de sante (health house) in 1846. PMID- 27412973 TI - Abces cutane a Acremonium. PMID- 27412972 TI - Management of scorpion stings in Africa and the Mediterranean region. AB - Common in the southern and eastern Mediterranean basin, scorpion stings can develop into a severe medical emergency, especially in young children. Here we review several principles of diagnosis and treatment. The indications for antivenom and symptomatic treatment are detailed according to the symptoms and clinical severity of envenomation. PMID- 27412974 TI - Limb reconstructive surgery in austere settings: use of flaps in French forward surgical facilities. AB - INTRODUCTION: Military surgeons deployed abroad must achieve soft tissue coverage under austere conditions. HYPOTHESIS: A non-specialized surgeon can achieve soft tissue coverage with good results. MATERIAL AND METHOD: This is a retrospective study of all patients who underwent soft tissue coverage in French forward surgical units between 2003 and 2013. RESULTS: In all, 81 flaps were constructed. Open fractures (39%) were the leading indication, followed by osseous infections (35%). Most flaps were for legs (70%) and hands (25%). Only pedicle flaps were used. The success rate was 91%. DISCUSSION: Flaps can be constructed by orthopedic surgeons who are not specialized in reconstructive surgery, in austere settings and with good results. This procedure must be part of a global strategy of limb reconstruction, especially in cases of bone and joint infection. Pedicle flaps, especially muscular, appear more reliable and are to be preferred. The training of the surgeons deployed abroad must include flap surgery. PMID- 27412975 TI - Larval vomiting during a mission in Haiti. AB - Following an original case report of massive regurgitation of maggots and the difficulty of medical management, we return to the fecal contamination problem for troops in the field. The survey of maggots has allowed for the diagnosis of contamination by ingestion of house fly eggs as a major infection vector. The successive ingestion of anti-acid and gastric dressing can induce an important diminution of gastric acidity that can allow for the proliferation of germs. In an operational context or natural catastrophe andin addition to field hygiene rules that are very important, it can also be useful to propose exclusive field rationsfor few daysin order to limit the interhuman contamination. PMID- 27412976 TI - Zika virus infections. AB - Since its discovery in 1947 in Uganda, the Zika virus (ZIKV) remained in the shadows emerging in 2007 in Micronesia, where hundreds of dengue-like syndromes were reported. Then, in 2013-2014, it was rife in French Polynesia, where the first neurological effects were observed. More recently, its arrival in Brazil was accompanied by an unusually high number of children with microcephaly born to mothers infected with ZIKV during the first trimester of pregnancy. In 2016, the World Health Organization declared ZIKV infection to be a public health emergency and now talks about a ZIKV pandemic. This review aims to summarize the current knowledge about ZIKV infection, successively addressing its transmission, epidemiology, clinical aspects, diagnosis, treatment, and prevention before discussing some perspectives. PMID- 27412977 TI - Epidemiological and clinical analysis of hepatitis virus A infections during three successive outbreaks in Sfax (Tunisia) between 2007 and 2010. AB - to describe the epidemiological and clinical characteristics of HAV infection during three successive outbreaks occurring between 2007 and 2010 in the governorate of Sfax. epidemiological and clinical characteristics were retrospectively analyzed from the outbreak investigations. The diagnosis of acute hepatitis A was confirmed by ELISA detection of immunoglobulin M serum antibodies to HAV. 443 patients were identified and 159 of them investigated. Their mean age was 12.2 years and the M/F ratio was 0.9. The most affected age groups were 6-10 years (35%) and 11-15 years (33%). The most likely sources of contamination were drinking water from wells or tanks and direct transmission. The most frequent symptoms included asthenia, digestive disorders, and jaundice. Two cases of fulminant hepatitis were reported, one lethal. our results show that HAV endemicity in the governorate of Sfax has dropped from high to intermediate as demonstrated by the increasing age at primary HAV infection. Strengthening health education and improving access to drinking water would reduce the transmission risk of HAV in our regions. PMID- 27412978 TI - Seroepidemiology of HIV, syphilis and hepatitis B and C viruses among blood donors in Bangui, Central African Republic. AB - The aim of this study was to determine the seroprevalence of HIV, the hepatitis B and C viruses, and syphilis as well the risk factors for these diseases among blood donors in Bangui, Central Africa Republic. This cross-sectional study examined samples from donors giving blood in August and September, 2013. HIV1/2 antibodies was screened with the Determine and Unigold HIV tests. Hepatitis B surface antigens were detected by sandwich immunochromatographic methods (DIAspot HBsAg test), and antibodies to HCV by the DIAspot test strip. Syphilis was diagnosed with the VDRL and TPHA methods (Omega Diagnostic, UK). The Chi(2) test was used for statistical analysis. The study included samples from 551 individuals, 350 (63.52%) of whom were frequent volunteer donors. In all, 132 (23.95%) were infected with at least one pathogen. The overall seroprevalence rate was 8.89% for HBV, 4.72% for HCV, 4.36% for syphilis, and 5.98% for HIV. Eight patients had two concomitant infections, with HIV-HBV the most common combination. Compared to long-term volunteers, first-time donors were more often infected by at least one of the pathogens we screened for, most especially HVB (OR = 5.06; 95% CI = 4.22-7.11) and syphilis (OR = 2.05; 95% CI = 2.02-7.44). Our findings indicate the high seroprevalence of transfusion-transmitted infections in blood donated in Bangui. The most common combined infections were HIV-HBV. The most common risk factor was a family history of HBV infection, and especially, mother-child transmission. PMID- 27412979 TI - Cholera in pregnant women: the 2012 epidemic at the reference center at the Donka National Hospital in Conakry. AB - Cholera is an epidemic diarrheal disease transmitted through the digestive tract; it can cause obstetric complications in pregnant women. The objective of this study was to describe the epidemiological, clinical, and therapeutic aspects of cholera in pregnant women, as well as its course, during the 2012 epidemic in Conakry. This retrospective, descriptive studied examined the records of this epidemic over a 7-month period (from May 15 to December 15, 2012). Of 2,808 cholera patients at our hospital, 80 were pregnant, that is, 2.85%. Their mean age was 30 years [range: 15-45 years], 94% were from Conakry (94%), and 69% were in the third trimester of pregnancy. Choleriform diarrhea and vomiting were the main signs, found respectively in 100% and 95% of the women; dehydration was mild for 16%, moderate for 45%, and severe for 39%. Support consisted of rehydration, by plans A (16%), B (45%) or C (39%) and antibiotic treatment based on erythromycin (85%), doxycycline (14%), or azithromycin (1%). Other drugs that were used included phloroglucinol-trimethylphloroglucinol (Spasfon((r))) for 45%, acetaminophen for 65%, and iron/folic acid for 1% of cases. The major obstetric complications were 4 intrauterine deaths (5%), 2 cases of threatened abortion (2%), 1 preterm delivery (1%), and 1 maternal death. The cholera outbreak in 2012 affected a large number of pregnant women in Conakry, most during their third trimester. The classic clinical manifestations were associated with obstetric complications and maternal-fetal risks. PMID- 27412980 TI - Microbiological characteristics of community-acquired peritonitis at Souro Sanou Teaching Hospital of Bobo Dioulasso. AB - The purpose of this study was to describe the microbiological characteristics of community-acquired peritonitis at the Souro Sanou teaching hospital of Bobo Dioulasso, Burkina Faso. This 10-month prospective study, from July 2012 through May 2013 included all cases of community-acquired peritonitis who underwent surgery at our hospital and had a pus sample taken at that time. Bacteriological analyses were performed according to the hospital laboratory's protocol. The study included 72 patients (45 men and 27 women with a sex-ratio of 1.6). Their mean age was 27.3 years (range: 14 months to 67 years). The analysis of 72 samples of pus enabled confirmation of 39 cases and led to the identification of 53 bacterial strains. The most common families were enterobacteriaceae in 58% and Gram-positive cocci in 36%. The most common enterobacteria species was Escherichia coli (47%) followed by Streptococcus species (22%). The microbiological confirmation of peritonitis was most frequent in the 20-30 year old age group. These bacteria appeared most susceptible to gentamycin, ceftriaxone, and ciprofloxacin, while we observed resistance to amoxicillin and the combination of clavulanic acid-amoxicillin. These findings suggest that the best probabilistic antibiotic treatment for the peritonitis in our context would combine a third-generation cephalosporin with aminoglycosides, with imidazole to cover potential anaerobic bacteria. PMID- 27412981 TI - Preventive measures to prevent loss to follow-up in highly active antiretroviral therapy (HAART): implementing a strategy in Ziguinchor (Casamance, Senegal) in 2014. AB - Since 2010, the Pharmacie et Aide Humanitaire (PAH) in Casamance (Senegal) has been maintaining a software package (Tacojo) that allows monthly monitoring of the distribution of treatment to every patient with HIV infection receiving highly active antiretroviral therapy (HAART). We used this program to set up measures to prevent the loss to follow-up of patients receiving HAART. Our involvement focused on two main areas. First, each patient is routinely contacted after inclusion, to help us to understand the patient's experience of the disease and the treatment. This process aims to improve adherence to the treatment. Then, all patients who miss an appointment are routinely contacted by telephone within seven days of that appointment. The goal is to understand the reasons for the absence and to encourage patients to continue their treatment. Despite the lack of distance due to the relative newness of this program, these preventive measures have shown hopeful results (80% of the patients came back after a call). It would be interesting to apply it in a sustainable manner and in more medical facilities. PMID- 27412982 TI - Refeeding syndrome: a forgotten and potentially lethal entity. AB - Refeeding syndrome (RS) is defined as the fluid, electrolyte, metabolic, and clinical disturbances that occur after nutrition of patients who have been undernourished or fasting for a prolonged period. This syndrome has been recognized for several decades but is most often overlooked and underdiagnosed by health professionals. The authors report a RS in a patient subjected to prolonged fasting after being kidnapped by a criminal gang. Refeeding resulted in severe hypophosphatemia, neurological impairments, and hematologic disorders. The patient died due to septic shock with multiple organ failure secondary to aspiration pneumonia. In this case, the failure to recognize RS was decisive in the fatal outcome. Professionals must be aware of this disease to prevent and treat it properly. PMID- 27412983 TI - Child abuse: an underestimated health problem? A case report from Cameroon. AB - Physical abuse of children can be of varying nature. Children can be shaken, beaten, burnt, or cut by their parents or guardians. The incidence of trauma inflicted on children is underestimated in many countries, probably because clinical signs are misjudged, as this case report shows. This three-year-old boy was seen in several health facilities of Yaounde, Cameroon. He was treated erroneously for severe malaria and then for meningitis because he presented with neurologic signs, before the diagnosis of child abuse was made. This was confirmed after an imaging work-up revealed fractures of the skull and the leg. The diagnosis was therefore delayed by at least six weeks from the date of the first consultation. This case report demonstrates that child abuse is not well known in our environment, and it is therefore crucial to train those who provide health care to children to recognize it. PMID- 27412984 TI - Metabolic Syndrome, Redox State, and the Proteasomal System. AB - SIGNIFICANCE: Since the metabolic syndrome (MS) and pathologies associated with/resulting from metabolic dysregulations became a worldwide spreading and growing problem, the mechanisms mediating the according cellular changes got into a focus of interest. The ubiquitin-proteasomal system (UPS) is the main regulator of both the functional and dysfunctional protein pool of (not only) mammalian cells-thus, it is obvious that an impact on this system may also affect cellular functionality that directly depends on permanent regulation/adaption of the cell's proteostasis. However, the according research is still at the beginning. Recent Advances: It was also recently shown that maintaining a highly functional UPS positively correlates with increased health or even life span, thus modulation or restoration of UPS function may be an effective approach alleviating or even preventing MS detrimental consequences. CRITICAL ISSUES: Even if many consequences of metabolic dysregulation such as a slight but chronic redox shift to a more oxidative state (i.e., a low-grade systemic inflammation that increases reactive oxygen species formation, lipid peroxidation, protein oxidation, formation of advanced glycation end products, glycosylation, S glutathionylation, redox shifts, endoplasmic reticulum stress, unfolded protein response, expression of transcription factors, and release of cytokines) are already known to affect the highly redox-regulated UPS, experimental data about UPS changes that are directly mediated by glucotoxic and/or lipotoxic stress are still rarely published. FUTURE DIRECTIONS: It may be taken into account that many MS-related pathologic changes result from UPS dysfunction or dysregulation. In this review, the main interface between MS effects and their impact on the UPS are highlighted since they may direct to new therapeutic approaches. Antioxid. Redox Signal. 25, 902-917. PMID- 27412985 TI - Whole Genome Comparison of Thermus sp. NMX2.A1 Reveals Principle Carbon Metabolism Differences with Closest Relation Thermus scotoductus SA-01. AB - Genome sequencing of the yellow-pigmented, thermophilic bacterium Thermus sp. NMX2.A1 resulted in a 2.29 Mb draft genome that encodes for 2312 proteins. The genetic relationship between various strains from the genus Thermus was assessed based on phylogenomic analyses using a concatenated set of conserved proteins. The resulting phylogenetic tree illustrated that Thermus sp. NMX2 A.1 clusters together with Thermus scotoductus SA-01, despite being isolated from vastly different geographical locations. The close evolutionary relationship and metabolic parallels between the two strains has previously been recognized; however, neither strain's genome data were available at that point in time. Genomic comparison of the Thermus sp. NMX2.A1 and T. scotoductus SA-01, as well as other closely related Thermus strains, revealed a high degree of synteny at both the genomic and proteomic level, with processes such as denitrification and natural cell competence appearing to be conserved. However, despite this high level of similarity, analysis revealed a complete, putative Calvin-Benson-Bassham (CBB) cycle in NMX2.A1 that is absent in SA-01. Analysis of horizontally transferred gene islands provide evidence that NMX2 selected these genes due to pressure from its HCO3 (-) rich environment, which is in stark contrast to that of the deep subsurface isolated SA-01. PMID- 27412986 TI - Ligand-Bound GeneSwitch Causes Developmental Aberrations in Drosophila that Are Alleviated by the Alternative Oxidase. AB - Culture of Drosophila expressing the steroid-dependent GeneSwitch transcriptional activator under the control of the ubiquitous alpha-tubulin promoter was found to produce extensive pupal lethality, as well as a range of dysmorphic adult phenotypes, in the presence of high concentrations of the inducing drug RU486. Prominent among these was cleft thorax, seen previously in flies bearing mutant alleles of the nuclear receptor Ultraspiracle and many other mutants, as well as notched wings, leg malformations, and bristle abnormalities. Neither the alpha tubulin-GeneSwitch driver nor the inducing drug on their own produced any of these effects. A second GeneSwitch driver, under the control of the daughterless promoter, which gave much lower and more tissue-restricted transgene expression, exhibited only mild bristle abnormalities in the presence of high levels of RU486. Coexpression of the alternative oxidase (AOX) from Ciona intestinalis produced a substantial shift in the developmental outcome toward a wild-type phenotype, which was dependent on the AOX expression level. Neither an enzymatically inactivated variant of AOX, nor GFP, or the alternative NADH dehydrogenase Ndi1 from yeast gave any such rescue. Users of the GeneSwitch system should be aware of the potential confounding effects of its application in developmental studies. PMID- 27412987 TI - Analyses of Compact Trichinella Kinomes Reveal a MOS-Like Protein Kinase with a Unique N-Terminal Domain. AB - Parasitic worms of the genus Trichinella (phylum Nematoda; class Enoplea) represent a complex of at least twelve taxa that infect a range of different host animals, including humans, around the world. They are foodborne, intracellular nematodes, and their life cycles differ substantially from those of other nematodes. The recent characterization of the genomes and transcriptomes of all twelve recognized taxa of Trichinella now allows, for the first time, detailed studies of their molecular biology. In the present study, we defined, curated, and compared the protein kinase complements (kinomes) of Trichinella spiralis and T. pseudospiralis using an integrated bioinformatic workflow employing transcriptomic and genomic data sets. We examined how variation in the kinome might link to unique aspects of Trichinella morphology, biology, and evolution. Furthermore, we utilized in silico structural modeling to discover and characterize a novel, MOS-like kinase with an unusual, previously undescribed N terminal domain. Taken together, the present findings provide a basis for comparative investigations of nematode kinomes, and might facilitate the identification of Enoplea-specific intervention and diagnostic targets. Importantly, the in silico modeling approach assessed here provides an exciting prospect of being able to identify and classify currently unknown (orphan) kinases, as a foundation for their subsequent structural and functional investigation. PMID- 27412988 TI - From Genotype to Phenotype: Nonsense Variants in SLC13A1 Are Associated with Decreased Serum Sulfate and Increased Serum Aminotransferases. AB - Using genomic applications to glean insights into human biology, we systematically searched for nonsense single nucleotide variants (SNVs) that are rare in the general population but enriched in the Old Order Amish (Amish) due to founder effect. We identified two nonlinked, nonsense SNVs (R12X and W48X) in SLC13A1 (allele frequencies 0.29% and 0.74% in the Amish; enriched 1.2-fold and 3.7-fold, compared to the outbred Caucasian population, respectively). SLC13A1 encodes the apical sodium-sulfate cotransporter (NaS1) responsible for sulfate (re)absorption in the kidneys and intestine. SLC13A1 R12X and W48X were independently associated with a 27.6% (P = 2.7 * 10(-8)) and 27.3% (P = 6.9 * 10( 14)) decrease in serum sulfate, respectively (P = 8.8 * 10(-20) for carriers of either SLC13A1 nonsense SNV). We further performed the first exome- and genome wide association study (ExWAS/GWAS) of serum sulfate and identified a missense variant (L348P) in SLC26A1, which encodes the basolateral sulfate-anion transporter (Sat1), that was associated with decreased serum sulfate (P = 4.4 * 10(-12)). Consistent with sulfate's role in xenobiotic detoxification and protection against acetaminophen-induced hepatotoxicity, SLC13A1 nonsense SNV carriers had higher aminotransferase levels compared to noncarriers. Furthermore, SLC26A1 L348P was associated with lower whole-body bone mineral density (BMD) and higher serum calcium, consistent with the osteochondrodysplasia exhibited by dogs and sheep with naturally occurring, homozygous, loss-of-function mutations in Slc13a1 This study demonstrates the power and translational potential of systematic identification and characterization of rare, loss-of-function variants and warrants additional studies to better understand the importance of sulfate in human physiology, disease, and drug toxicity. PMID- 27412989 TI - Ezetimibe-Statin Combination Therapy. AB - BACKGROUND: To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. METHODS: This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. RESULTS: Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). CONCLUSION: In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups. PMID- 27412991 TI - Morphological Variants Forgotten. PMID- 27412990 TI - Outpatient Antibiotic Prescription. AB - BACKGROUND: In view of the rise in antibiotic resistance and Clostridium difficile superinfection, close monitoring of antibiotic prescribing practices is essential so that targeted quality assurance measures can be taken. METHODS: We analyzed nationwide data from multiple statutory health insurance carriers on prescriptions of systemic antibiotics in the years 2008-2014, with special attention to cephalosporins and fluoroqinolones. Prescribing rates were characterized in terms of defined daily doses (DDD) per 1000 statutory insurees per year and were analyzed separately for each age group and each federal state in Germany. Trends were analyzed with joinpoint regression. RESULTS: Antibiotic prescribing rates for persons aged 15 to 69 increased slightly overall during the period of observation. On the other hand, there was a significant decline in antibiotic prescribing rates for persons under age 15 in all of the German states, with a mean annual decrease of 6.8%. There was also a slight decline in antibiotic prescribing rates for persons aged 70 and above, mainly accounted for by fluoroquinolones. Cephalosporin prescribing rates rose significantly in all states, by an overall average of 7.6% per annum. Cephalo - sporin prescribing rates rose significantly in all age groups except persons under age 15, for whom there was a decline that did not reach statistical significance. CONCLUSION: This study revealed an overall decline in outpatient antibiotic prescriptions for persons under age 15 as well as other major changes in prescribing practices for the types of antibiotics studied. The observed marked rise in cephalosporin prescribing rates in all German states demands special attention because of the associated danger of increased antibiotic resistance and C. difficile superinfection. Oral cephalosporins are not recommended as drugs of first choice in current guidelines. PMID- 27412992 TI - Co-factor Ureaplasma urealyticum. PMID- 27412993 TI - In Reply. PMID- 27412994 TI - Psychosomatic Aspects. PMID- 27412995 TI - In Reply. PMID- 27412996 TI - Letter: cardiovascular complications in patients with transjugular intrahepatic portosystemic shunt - the necessity for regular cardiac surveillance. PMID- 27412997 TI - Letter: cardiovascular complications in patients with transjugular intrahepatic portosystemic shunt - the necessity for regular cardiac surveillance. Authors' reply. PMID- 27412998 TI - Letter: risk factor and mortality of peptic ulcer disease. PMID- 27412999 TI - Letter: risk factors and impacts of psychological morbidity in young people with inflammatory bowel disease. PMID- 27413000 TI - Letter: risk factor and mortality of peptic ulcer disease - authors' reply. PMID- 27413001 TI - Letter: risk factors and impacts of psychological morbidity in young people with inflammatory bowel disease - authors' reply. PMID- 27413003 TI - Mass-forming venous malformation of the cecum. PMID- 27413002 TI - Pulmonary changes in Norwegian fatal cases of pandemic influenza H1N1 (2009) infection: a morphologic and molecular genetic study. AB - BACKGROUND: During the pandemic outbreak of the 2009 swine influenza (A(H1N1)pdm09), 32 fatal cases occurred in Norway and 19 of these were included in this study. OBJECTIVES: We characterised pulmonary changes in these fatal Norwegian cases. PATIENTS AND METHODS: Upon hospitalisation, detailed clinical information and specimens from the upper and lower respiratory pathways were collected. At post-mortem, lung tissue was collected, formalin-fixed and paraffin embedded. Immunohistochemical and light microscopic examination was performed to visualise the local expression of the A(H1N1)pdm09 virus. Reverse transcription polymerase chain reaction (RT-PCR) and pyrosequencing of the non-fixed specimens allowed the identification of mutations in the influenza virus surface glycoprotein (haemagglutinin gene) particularly at position 222. RESULTS AND CONCLUSIONS: The overall course of illness lasted from 2 to 40 days (median 9 days). Diffused alveolar damage (DAD) was evident in 11 cases, 4 of which had no apparent underlying illness. Obesity was prominent in 12 cases, where three individuals were classified as otherwise healthy. The HA D222G mutation was detected in six cases, 3 of which had no underlying illness. Immunohistochemistry showed the A(H1N1)pdm09 virus to be prominent at the site of inflammation both in close proximity to and inside alveolar structures in the lung tissue. In addition to a possible role for the HA D222G mutation, our findings indicate that host factors and underlying conditions in the infected individuals are fundamental for disease outcome in many cases. This study increases our understanding of determinants for the clinical outcome of pandemic influenza, which could guide future treatment. PMID- 27413004 TI - Drunkenness and heavy drinking among 11year olds - Findings from the UK Millennium Cohort Study. AB - Heavy drinking among young people is linked to negative consequences including other risky behaviours, educational failure and premature mortality. There is a lack of research examining factors that influence heavy and binge drinking in early adolescence as prior work has focused on older teenagers. The objective of this paper was to identify individual and family factors associated with drunkenness and episodes of heavy drinking in early adolescence. We analysed data on 11,046 11year olds from the UK Millennium Cohort Study. Multivariate logistic regression was used to estimate odds ratios for associations. 1.2% of participants reported having been drunk, and 0.6% reported having had 5 or more drinks in a single episode. Participants who reported drunkenness were more likely to be boys (1.6% vs 0.7%, p<0.01), to have socioemotional difficulties (2.6% vs 1.0%, p<0.001), to report antisocial behaviours (none=0.6%, 1=2.0%, 2 or more=7.0%, p<0.001), report truancy (6.0% vs 1.0%, p<0.001), smoke cigarettes (12.0% vs 0.8%, p<0.001). Parental drinking did not appear to be associated with the odds of drunkenness. Associated with higher odds of drunkenness were: having friends who drank (OR=5.17); having positive expectancies towards alcohol (OR 2+=2.02); ever having smoked cigarettes (OR=5.32); the mother-child relationship not being close (OR=2.17). Associated with a reduced odds of drunkenness was having a heightened perception of harm from drinking 1-2 drinks daily (OR - some risk=0.48, great risk=0.40). Our findings support policies aimed at multiple levels, starting in the preadolescent years, which incorporate individual, family, and peer factors. PMID- 27413005 TI - A systematic review of interventions to improve adherence to statin medication: What do we know about what works? AB - Suboptimal adherence to statin medication is common and leads to serious negative health consequences but may respond to intervention. This review evaluated the effectiveness of interventions intended to improve adherence to statin medication. Data sources included peer-reviewed publications from Cochrane Register of Randomized Controlled Trials (RCTs), PubMed, CINAHL, and EMBase indexed between 01 October 2008 and 18 October 2015 and studies from reference lists and technical experts. RCTs that evaluated an intervention targeting adherence to self-administered statin medication for primary or secondary prevention were eligible. Two investigators independently reviewed trials, extracted data, and evaluated risk of bias. Twenty-nine RCTs reporting on 39,769 patients met inclusion. Identified RCTs exhibited methodological weaknesses: all but one failed to set inclusion parameters for medication adherence; nearly half lacked sufficient power to detect meaningful effects; and the majority had a risk of bias. Interventions were categorized into five classes (simplification of regimen, prescription cost coverage, reminders, education and information, and multi-faceted) and effects were pooled within each class. Prescription cost coverage, Hedges' g=0.15, 95%CI [0.11:0.21], simplification of drug regimen, Hedges' g=0.38, 95%CI [0.22:0.55], the provision of education, Hedges' g=0.19, 95%CI [0.01:0.37], and the use of multi-faceted interventions, Hedges' g=0.16, 95%CI [0.05:0.27], had small positive effects on statin adherence relative to usual care and reminders were promising, Hedges' g=0.0.27, 95%CI [-0.05:0.60]. In conclusion, there are some successful interventions to improve adherence to statin medication but the effects are small and additional methodologically rigorous trials are needed. PMID- 27413007 TI - Interventions to reduce social isolation and loneliness among older people: an integrative review. AB - Loneliness and social isolation are major problems for older adults. Interventions and activities aimed at reducing social isolation and loneliness are widely advocated as a solution to this growing problem. The aim of this study was to conduct an integrative review to identify the range and scope of interventions that target social isolation and loneliness among older people, to gain insight into why interventions are successful and to determine the effectiveness of those interventions. Six electronic databases were searched from 2003 until January 2016 for literature relating to interventions with a primary or secondary outcome of reducing or preventing social isolation and/or loneliness among older people. Data evaluation followed Evidence for Policy and Practice Information and Co-ordinating Centre guidelines and data analysis was conducted using a descriptive thematic method for synthesising data. The review identified 38 studies. A range of interventions were described which relied on differing mechanisms for reducing social isolation and loneliness. The majority of interventions reported some success in reducing social isolation and loneliness, but the quality of evidence was generally weak. Factors which were associated with the most effective interventions included adaptability, a community development approach, and productive engagement. A wide range of interventions have been developed to tackle social isolation and loneliness among older people. However, the quality of the evidence base is weak and further research is required to provide more robust data on the effectiveness of interventions. Furthermore, there is an urgent need to further develop theoretical understandings of how successful interventions mediate social isolation and loneliness. PMID- 27413006 TI - Optogenetic study of networks in epilepsy. AB - Currently, approximately 30% of patients with epilepsy do not have adequate seizure control. A greater understanding of the underlying mechanisms by which seizures start or propagate could lead to new therapeutic strategies. The recent development of optogenetics, because of its unprecedented precision for controlling activity within distinct neuronal populations, has revolutionized neuroscience, including epilepsy research. This Review discusses recent breakthroughs made with optogenetics in epilepsy research. These breakthroughs include new insights into the key roles that different cell types play in mediating seizures as well as in the development of epilepsy. Subsequently, we discuss how targeting different brain regions and cell populations has opened up the possibility of highly specific therapies that can stop seizures on demand. Finally, we illustrate how combining newly available neuroscience tools with whole-brain imaging techniques will allow researchers to understand better the spread of seizures on a network level. (c) 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID- 27413008 TI - The RhoE/ROCK/ARHGAP25 signaling pathway controls cell invasion by inhibition of Rac activity. AB - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of skeletal muscle origin in children and adolescents. Among RMS subtypes, alveolar rhabdomyosarcoma (ARMS), which is characterized by the presence of the PAX3-FOXO1A or PAX7-FOXO1A chimeric oncogenic transcription factor, is associated with poor prognosis and a strong risk of metastasis compared with the embryonal subtype (ERMS). To identify molecular pathways involved in ARMS aggressiveness, we first characterized the migratory behavior of cell lines derived from ARMS and ERMS biopsies using a three-dimensional spheroid cell invasion assay. ARMS cells were more invasive than ERMS cells and adopted an ellipsoidal morphology to efficiently invade the extracellular matrix. Moreover, the invasive potential of ARMS cells depended on ROCK activity, which is regulated by the GTPase RhoE. Specifically, RhoE expression was low in ARMS biopsies, and its overexpression in ARMS cells reduced their invasion potential. Conversely, ARHGAP25, a GTPase-activating protein for Rac, was up-regulated in ARMS biopsies. Moreover, we found that ARHGAP25 inhibits Rac activity downstream of ROCKII and is required for ARMS cell invasion. Our results indicate that the RhoE/ROCK/ARHGAP25 signaling pathway promotes ARMS invasive potential and identify these proteins as potential therapeutic targets for ARMS treatment. PMID- 27413009 TI - Variants of the yeast MAPK Mpk1 are fully functional independently of activation loop phosphorylation. AB - MAP kinases of the ERK family are conserved from yeast to humans. Their catalytic activity is dependent on dual phosphorylation of their activation loop's TEY motif, catalyzed by MAPK kinases (MEKs). Here we studied variants of Mpk1, a yeast orthologue of Erk, which is essential for cell wall integrity. Cells lacking MPK1, or the genes encoding the relevant MEKs, MKK1 and MKK2, do not proliferate under cell wall stress, imposed, for example, by caffeine. Mutants of Mpk1, Mpk1(Y268C) and Mpk1(Y268A), function independently of Mkk1 and Mkk2. We show that these variants are phosphorylated at their activation loop in mkk1?mkk2? and mkk1?mkk2?pbs2?ste7? cells, suggesting that they autophosphorylate. However, strikingly, when Y268C/A mutations were combined with the kinase-dead mutation, K54R, or mutations at the TEY motif, T190A+Y192F, the resulting proteins still allowed mkk1?mkk2? cells to proliferate under caffeine stress. Mutating the equivalent residue, Tyr-280/Tyr-261, in Erk1/Erk2 significantly impaired Erk1/2's catalytic activity. This study describes the first case in which a MAPK, Erk/Mpk1, imposes a phenotype via a mechanism that is independent of TEY phosphorylation and an unusual case in which an equivalent mutation in a highly conserved domain of yeast and mammalian Erks causes an opposite effect. PMID- 27413011 TI - Distinct isoform-specific complexes of TANGO1 cooperatively facilitate collagen secretion from the endoplasmic reticulum. AB - Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER. Moreover, we found that each of the TANGO1 isoforms forms a stable protein complex with factors involved in collagen secretion: TANGO1L/cTAGE5/Sec12 (900 kDa) and TANGO1S/cTAGE5/Sec12 (700 kDa). Of interest, TANGO1S and TANGO1L seemed to be interchangeable in exporting collagen from the ER. Our results suggest that mammalian ER exit sites possess two different-sized membrane-bound macromolecular complexes that specifically function in large-cargo export from the ER. PMID- 27413010 TI - Sec24C/D-isoform-specific sorting of the preassembled ER-Golgi Q-SNARE complex. AB - Secretory proteins are exported from the endoplasmic reticulum in COPII vesicles. SNARE proteins-core machinery for membrane fusion-are incorporated into COPII vesicles by direct interaction with Sec24. Here we report a novel mechanism for sorting of the ER-Golgi Q-SNAREs into COPII vesicles. Different mammalian Sec24 isoforms recruit either the R-SNARE Sec22b or the Q-SNAREs Syntaxin5, GS27, and Bet1. Syntaxin5 is the only Q-SNARE that directly interacts with Sec24C, requiring its "open" conformation. Mutation within the IxM cargo-binding site of Sec24C led to a drastic reduction in sorting of all three Q-SNAREs into COPII vesicles, implying their ER export as a preassembled complex. Analysis of immunoisolated COPII vesicles and intracellular localization of Sec24 isoforms indicate that all ER-Golgi SNAREs are present on the same vesicle. Combined with existing data, our findings yield a general concept of how Sec24 isoforms can recruit fusogenic SNARE subunits to keep them functionally apart and thus prime mammalian COPII vesicles for homotypic fusion. PMID- 27413012 TI - Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care. AB - OBJECTIVE: To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones). DESIGN: Open cohort study. SETTING: 1243 general practices contributing data to the QResearch database in England. PARTICIPANTS: 469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. EXPOSURES: Diabetes drugs (glitazones, gliptins, metformin, sulphonylureas, insulin, other) alone and in combination. MAIN OUTCOME MEASURE: First recorded diagnoses of cardiovascular disease, heart failure, and all cause mortality recorded on the patients' primary care, mortality, or hospital record. Cox proportional hazards models were used to estimate hazard ratios for diabetes treatments, adjusting for potential confounders. RESULTS: During follow-up, 21 308 patients (4.5%) received prescriptions for glitazones and 32 533 (6.9%) received prescriptions for gliptins. Compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular disease; corresponding values for glitazones were significantly decreased risks of 23% for all cause mortality, 26% for heart failure, and 25% for cardiovascular disease. Compared with no current treatment, there were no significant associations between monotherapy with gliptins and risk of any complications. Dual treatment with gliptins and metformin was associated with a decreased risk of all three outcomes (reductions of 38% for heart failure, 33% for cardiovascular disease, and 48% for all cause mortality). Triple treatment with metformin, sulphonylureas, and gliptins was associated with a decreased risk of all three outcomes (reductions of 40% for heart failure, 30% for cardiovascular disease, and 51% for all cause mortality). Compared with no current treatment, monotherapy with glitazone was associated with a 50% decreased risk of heart failure, and dual treatment with glitazones and metformin was associated with a decreased risk of all three outcomes (reductions of 50% for heart failure, 54% for cardiovascular disease, and 45% for all cause mortality); dual treatment with glitazones and sulphonylureas was associated with risk reductions of 35% for heart failure and 25% for cardiovascular disease; triple treatment with metformin, sulphonylureas, and glitazones was associated with decreased risks of all three outcomes (reductions of 46% for heart failure, 41% for cardiovascular disease, and 56% for all cause mortality). CONCLUSIONS: There are clinically important differences in risk of cardiovascular disease, heart failure, and all cause mortality between different diabetes drugs alone and in combination. Overall, use of gliptins or glitazones was associated with decreased risks of heart failure, cardiovascular disease, and all cause mortality compared with non-use of these drugs. These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, might have implications for prescribing of diabetes drugs. PMID- 27413013 TI - Validity of the Delirium Observation Screening Scale in Identifying Delirium in Home Hospice Patients. AB - BACKGROUND: Delirium is common in home hospice patients and conveys significant morbidity to both patients and caregivers. The Delirium Observation Screening Scale (DOS) was developed to improve delirium recognition but has yet to be validated in the home hospice setting. OBJECTIVE: This pilot study aimed to explore the accuracy of the DOS for identifying delirium in home hospice patients. DESIGN: Prospective delirium evaluation using a convenience sample. SETTING/PARTICIPANTS: Community hospice patients were approached for study inclusion. MEASUREMENTS: Participants were assessed using the Delirium Rating Scale-Revised-98 (DRS-R-98), with results being categorized as "delirium" or "no delirium." The Delirium Observation Screening Scale scores, completed by hospice nurses during weekly patient assessment visits, were compared to the DRS-R-98 results. RESULTS: Within this population, 30/78 (38%) assessments were categorized as delirious. In the majority of assessments, 69/75 (92%), the DRS-R 98 and DOS provided congruent results. There were 5 false positives and 1 false negative, demonstrating the DOS to be a clinically useful tool with a sensitivity of 0.97 and specificity of 0.89. CONCLUSION: The DOS appears to be an accurate way to screen for delirium in home hospice patients. Validation of the DOS may help to improve delirium recognition and treatment and has the potential to increase quality of life in this vulnerable population. This input will also be taken into consideration in the development of a systematic screening procedure for delirium diagnosis at our local hospice, which we hope will be generalizable to other hospice agencies. PMID- 27413014 TI - Cancer Transitional Care for Terminally Ill Cancer Patients Can Reduce the Number of Emergency Admissions and Emergency Department Visits. AB - BACKGROUND: Emergency admissions and emergency department visits (EAs/EDVs) have been used as quality indicators of home care in terminally ill cancer patients. We established a cancer transitional care (CTC) program to monitor and manage terminally ill cancer patients receiving care at home. The purpose of this study was to evaluate the effectiveness of CTC by the frequency of EAs/EDVs. METHODS: In a retrospective chart review, we identified 133 patients with cancer admitted to our department, of whom 56 met study eligibility criteria. The CTC consisted of at least 1 or more following components: (1) a 24-hour hotline for general physicians or home care nurses to reach hospital-based physicians, (2) periodic phone calls from an expert hospital-based oncology nurse to home care medical staff, and (3) reports sent to our department from home care medical staff. The primary outcome variable was the frequency of EAs/EDVs. RESULTS: There were 32 EAs/EDVs and 69 planned admissions during the observation period. In the last 30 days of life, 16 patients (28.6%) had 1 EA/EDV and none had multiple EAs/EDVs. Compared with previous studies, our study found a similar or lower frequency of EAs/EDVs. CONCLUSION: Our findings suggest that the implementation of CTC reduces the number of EAs/EDVs by replacing them with planned admissions. Further prospective studies to evaluate CTC are warranted. PMID- 27413015 TI - The effects of sous-vide cooking parameters on texture and cell wall modifications in two apple cultivars: A response surface methodology approach. AB - This work aimed at evaluating the effects of sous-vide cooking parameters, such as time and temperature and their interactions, on textural attributes of 'Mondial Gala' and 'Granny Smith' apple cultivars. For this, different response surface methodology-based models were developed. This methodology proved a suitable means for the assessment of changes in textural parameters and cell wall modifications during the processing of apples. 'Mondial Gala' fruit displayed better aptitude for the preservation of textural properties after high temperature processing conditions and were therefore apparently more suited to sous-vide cooking than 'Granny Smith' apples. Pectin methylesterase activity levels in 'Mondial Gala' apples were enhanced at mild temperatures and pectins in this cultivar displayed a lower degree of methylation. Therefore, the establishment of calcium-mediated linkages between cell wall polymers might have been favoured in 'Mondial Gala' apples, thus reinforcing tissues and improving the preservation of textural attributes, in comparison to 'Granny Smith' samples. PMID- 27413016 TI - Effects of high hydrostatic pressure and thermal processing on bioactive compounds, antioxidant activity, and volatile profile of mulberry juice. AB - The aim of this study was to investigate the effects of high hydrostatic pressure and thermal processing on microbiological quality, bioactive compounds, antioxidant activity, and volatile profile of mulberry juice. High hydrostatic pressure processing at 500 MPa for 10 min reduced the total viable count from 4.38 log cfu/ml to nondetectable level and completely inactivated yeasts and molds in raw mulberry juice, ensuring the microbiological safety as thermal processing at 85 C for 15 min. High hydrostatic pressure processing maintained significantly (p < 0.05) higher contents of total phenolic, total flavonoid and resveratrol, and antioxidant activity of mulberry juice than thermal processing. The main volatile compounds of mulberry juice were aldehydes, alcohols, and ketones. High hydrostatic pressure processing enhanced the volatile compound concentrations of mulberry juice while thermal processing reduced them in comparison with the control. These results suggested that high hydrostatic pressure processing could be an alternative to conventional thermal processing for production of high-quality mulberry juice. PMID- 27413017 TI - Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study. AB - OBJECTIVE: To determine the association between use of sulphonylureas and risk of hypoglycaemia in relation to renal function and sulphonylurea metabolic group compared with use of metformin. DESIGN: Population based cohort study using routinely collected data from general practices in England. SETTING: Clinical Practice Research Datalink (CPRD) database, 2004-12. PARTICIPANTS: 120 803 new users of a non-insulin antidiabetic agent with at least one prescription and aged 18 years or more. The first prescription defined start of follow-up. Patients were followed until the end of data collection, a record for hypoglycaemia, or a blood glucose level of less than 3.0 mmol/L. MAIN OUTCOME MEASURES: Associations between sulphonylurea dose, renal impairment, type of sulphonylurea used, and risk of hypoglycaemia, were determined using Cox proportional hazard models. Adjustments were made for age, sex, lifestyle, comorbidity, and drug use. RESULTS: The risk of hypoglycaemia in current users of sulphonylureas only was significantly increased compared with current users of metformin only (adjusted hazard ratio 2.50, 95% confidence interval 2.23 to 2.82). The higher risk in current users of sulphonylureas only was further increased in patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m(2) (4.96, 3.76 to 6.55). The risk of hypoglycaemia was also significantly higher in patients with a high sulphonylurea dose (3.12, 2.68 to 3.62) and in current users of glibenclamide (7.48, 4.89 to 11.44). Gliclazide, the sulphonylurea of first choice, showed a similar risk of hypoglycaemia compared with other sulphonylureas. CONCLUSIONS: Sulphonylurea treatment in patients with a renal function of less than 30 mL/min/1.73 m(2) should be considered with caution. Moreover, an increased risk of hypoglycaemic events was observed among all users of sulphonylureas. This contrasts with several guidelines that recommend gliclazide as first choice sulphonylurea, and therefore requires further investigation. PMID- 27413018 TI - Prevented Prescribing Errors in an ICU of a Brazilian Teaching Hospital Specializing in Women's Health. PMID- 27413019 TI - Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis. AB - Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age- and gender paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients. PMID- 27413020 TI - Activation of PPARbeta/delta prevents hyperglycaemia-induced impairment of Kv7 channels and cAMP-mediated relaxation in rat coronary arteries. AB - PPARbeta/delta activation protects against endothelial dysfunction in diabetic models. Elevated glucose is known to impair cAMP-induced relaxation and Kv channel function in coronary arteries (CA). Herein, we aimed to analyse the possible protective effects of the PPARbeta/delta agonist GW0742 on the hyperglycaemic-induced impairment of cAMP-induced relaxation and Kv channel function in rat CA. As compared with low glucose (LG), incubation under high glucose (HG) conditions attenuated the relaxation induced by the adenylate cyclase activator forskolin in CA and this was prevented by GW0742. The protective effect of GW0742 was supressed by a PPARbeta/delta antagonist. In myocytes isolated from CA under LG, forskolin enhanced Kv currents and induced hyperpolarization. In contrast, when CA were incubated with HG, Kv currents were diminished and the electrophysiological effects of forskolin were abolished. These deleterious effects were prevented by GW0742. The protective effects of GW0742 on forskolin-induced relaxation and Kv channel function were confirmed in CA from type-1 diabetic rats. In addition, the differences in the relaxation induced by forskolin in CA incubated under LG, HG or HG + GW0742 were abolished by the Kv7 channel inhibitor XE991. Accordingly, GW0742 prevented the down regulation of Kv7 channels induced by HG. Finally, the preventive effect of GW0742 on oxidative stress and cAMP-induced relaxation were overcome by the pyruvate dehydrogenase kinase 4 (PDK4) inhibitor dichloroacetate (DCA). Our results reveal that the PPARbeta/delta agonist GW0742 prevents the impairment of the cAMP-mediated relaxation in CA under HG. This protective effect was associated with induction of PDK4, attenuation of oxidative stress and preservation of Kv7 channel function. PMID- 27413021 TI - Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice. AB - Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon gamma-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury. PMID- 27413022 TI - The transclival artery: a variant persistent carotid-basilar arterial anastomosis not previously reported. AB - During embryological development, primitive anastomoses exist between the carotid and vertebrobasilar arteries. These anastomoses typically regress or are incorporated into the developing vasculature. Persistence beyond fetal development, however, results in vascular anomalies that alter haemodynamic flow with a predisposition for aneurysm formation. The carotid-vertebrobasilar anastomoses mirror the primitive communications and include (from most to least common) the trigeminal, hypoglossal, proatlantal and otic arteries. The hypoglossal and proatlantal variants extend through the hypoglossal canal or foramen magnum, respectively. We present a previously undescribed variant of these persistent fetal anastomoses, the 'transclival artery', which courses through its own transclival skull base canal/foramen. PMID- 27413023 TI - Bleeding heart: a case of spontaneous hemopericardium and tamponade in a hyperthyroid patient on warfarin. AB - We describe the case of an 81-year-old female, diagnosed with hyperthyroidism related atrial fibrillation. Given her CHA2DS2VASc score of 3, she was started on warfarin for stroke prevention. One month later, she was admitted with cardiac tamponade. This tamponade was suspected to be secondary to hemopericardium, based on the elevated international normalized ratio (INR), drop in haemoglobin and the radiodensity (55 HU) of the pericardial effusion on CT. The patient was a Jehovah's witness who therefore initially refused measures for reversing coagulopathy. Given her coagulopathy and absence of imminent haemodynamic compromise, pericardiocentesis was deferred. Unfortunately, 1 day later, the patient deteriorated rapidly. By the time pericardiocentesis was performed and factor VIIa administered, the patient had already started developing multiple organ failure. She developed cardiac arrest and died 3 days after her admission. Only 10 cases of hemopericardium attributable to warfarin have previously been reported. In this report, we review the literature and also describe how hyperthyroidism most likely predisposed our patient to bleeding complications from warfarin. PMID- 27413024 TI - Dilated aortic root and severe aortic regurgitation causing dilated cardiomyopathy in classic Ehlers-Danlos syndrome. AB - Ehlers-Danlos syndrome (EDS) is a group of heritable disorders characterised by vast clinical heterogeneity ranging from the classic constellation of symptoms including skin hyperextensibility, joint hypermobility and skin fragility to the exceedingly critical consequences of arterial rupture and visceral perforation. We describe the case of a 65-year-old male with a history of classic EDS who reported of dyspnoea on exertion, orthopnoea, fatigue and palpitations. He was found to have dilated cardiomyopathy with an ejection fraction of 35%, aortic root dilation and severe aortic valve regurgitation. The authors intend to draw attention to the rare cardiac manifestations of this condition and the therapeutic challenges involved in managing such patients. PMID- 27413025 TI - Necrotising fasciitis after acupuncture treatment in an immunocompetent patient. AB - A 42-year old male with no significant medical history was admitted to our hospital with a painful, red, swollen right arm and fever. The rash and swelling had started in the cubital fossa. 7 days earlier, needles had been placed exactly at that site during an acupuncture treatment. After deterioration of his condition, surgical exploration of the arm revealed necrotising fasciitis. Although acupuncture is a relatively safe intervention, serious complications do occur. Necrotising fasciitis after acupuncture has been described in immunocompromised patients. To the best of our knowledge this is the first immunocompetent patient with necrotising fasciitis and toxic shock, caused by acupuncture. PMID- 27413026 TI - Synchronised sartorius avulsions in adolescent sprinter. PMID- 27413027 TI - Automated Control of the Organic and Inorganic Composition of Aloe vera Extracts Using (1)H NMR Spectroscopy. AB - Recent classification of Aloe vera whole-leaf extract by the International Agency for Research and Cancer as a possible carcinogen to humans as well as the continuous adulteration of A. vera's authentic material have generated renewed interest in controlling A. vera. The existing NMR spectroscopic method for the analysis of A. vera, which is based on a routine developed at Spectral Service, was extended. Apart from aloverose, glucose, malic acid, lactic acid, citric acid, whole-leaf material (WLM), acetic acid, fumaric acid, sodium benzoate, and potassium sorbate, the quantification of Mg(2+), Ca(2+), and fructose is possible with the addition of a Cs-EDTA solution to sample. The proposed methodology was automated, which includes phasing, baseline-correction, deconvolution (based on the Lorentzian function), integration, quantification, and reporting. The NMR method was applied to 41 A. vera preparations in the form of liquid A. vera juice and solid A. vera powder. The advantages of the new NMR methodology over the previous method were discussed. Correlation between the new and standard NMR methodologies was significant for aloverose, glucose, malic acid, lactic acid, citric acid, and WLM (P < 0.0001, R(2) = 0.99). NMR was found to be suitable for the automated simultaneous quantitative determination of 13 parameters in A. vera. PMID- 27413028 TI - Health Risk Information Engagement and Amplification on Social Media. AB - Emerging pandemics call for unique health communication and education strategies in which public health agencies need to satisfy the public's information needs about possible risks while preventing risk exaggeration and dramatization. As a route to providing a framework for understanding public information behaviors in response to an emerging pandemic, this study examined the characteristics of communicative behaviors of social media audiences in response to Ebola outbreak news. Grounded in the social amplification of risks framework, this study adds to an understanding of information behaviors of online audiences by showing empirical differences in audience engagement with online health information. The data were collected from the Centers for Disease Control and Prevention (CDC) Facebook channel. The final data set included 809 CDC posts and 35,916 audience comments. The analysis identified the differences in audience information behaviors in response to an emerging pandemic, Ebola, and health promotion posts. While the CDC had fewer posts on Ebola than health promotion topics, the former received more attention from active page users. Furthermore, audience members who actively engaged with Ebola news had a small overlap with those who engaged with non-Ebola information during the same period. Overall, this study demonstrated that information behavior and audience engagement is topic dependent. Furthermore, audiences who commented on news about an emerging pandemic were homogenous and varied in their degree of information amplification. PMID- 27413029 TI - Mississippi Communities for Healthy Living. AB - BACKGROUND: Improving the diet of communities experiencing health inequities can be challenging given that multiple dietary components are low in quality. Mississippi Communities for Healthy Living was designed to test the comparative effectiveness of nutrition education using a single- versus multiple-message approach to improve the diet of adult residents in the Lower Mississippi Delta. METHOD: The single-message approach targeted discretionary calories while the multiple-message approach also targeted vegetables, fruits, whole grains, and lean protein. Delta food frequency questionnaires were used to measure participants' diet, while the Healthy Eating Index-2005 (HEI-2005) was used to generate diet quality scores. Generalized linear mixed model regression was used to test for significant time, treatment, and time * treatment interaction effects in HEI-2005 component and total score changes. RESULTS: The majority of participants in the single- and multiple-message arms ( n = 114 and 127, respectively) were female (88% and 96%, respectively), African American (90% and 98%, respectively), overweight or obese (92% and 87%, respectively), and 41 to 60 years of age (57% and 43%, respectively). Significant time effects were present for HEI-2005 total and component scores, with three exceptions-whole fruit, total grains, and saturated fat. Significant treatment effects were present for two components-total and whole fruit; scores were higher in the multiple-message approach arm as compared to the single-message approach arm across time points. No interaction effects were significant for any of the HEI-2005 scores. CONCLUSION: Focusing nutrition education on the discretionary calories component of the diet may be as effective as focusing on multiple components for improving diet quality. PMID- 27413030 TI - A Rare Pericardial Malignancy. PMID- 27413031 TI - Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease: A Clinical Conundrum. PMID- 27413032 TI - Heart Failure With a Better Ejection Fraction: Why Should We Care? PMID- 27413033 TI - Hashing It Out Over Cannabis: Moving Toward a Standard Guideline on Substance Use for Cardiac Transplantation Eligibility That Includes Marijuana. PMID- 27413034 TI - Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction. AB - BACKGROUND: There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease. METHODS AND RESULTS: A total of 376 patients with ejection fraction >=50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16+/-0.69 in HFpEF versus 2.54+/-0.80 in hypertensive controls; P<0.02 and 2.89+/-0.70 in normotensive controls; P<0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities. CONCLUSIONS: HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors. PMID- 27413035 TI - Antihyperglycemic Medication Use Among Medicare Beneficiaries With Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease. AB - BACKGROUND: Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood. METHODS AND RESULTS: Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m(2). Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71-83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5 35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2-7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m(2), 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran Mantel-Haenszel row-mean score test P=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (P<0.001). CONCLUSIONS: Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a thiazolidinedione, despite known concerns regarding HF. More research regarding safety and efficacy of various AHMs among HF patients is needed. PMID- 27413036 TI - Marijuana and Listing for Heart Transplant: A Survey of Transplant Providers. AB - BACKGROUND: There is no consensus within the heart transplant community about whether patients who use marijuana should be eligible for transplant listing, but several states have passed legislation prohibiting marijuana-using patients from being denied transplant listing based on their use of the substance. METHODS AND RESULTS: We conducted an independent, voluntary, web-based survey of heart and lung transplant providers to assess current practice patterns and attitudes toward marijuana use in patients with advanced heart failure being considered for transplant. A total of 360 heart transplant providers responded from 26 countries. Nearly two thirds of respondents (n=222, 64.4%) supported listing patients with advanced, end-stage heart failure for transplant who use legal medical marijuana. Significantly, fewer respondents (n=96, 27.5%) supported transplant listing for patients using legal recreational marijuana. The majority of providers currently make patients eligible for transplantation after a period of abstinence from marijuana (n=241, 68.3%). There were no differences between the proportion of respondents supporting transplant listing after stratification by profession or country/region. Most (78.4%) survey respondents from states with laws prohibiting marijuana-using patients from being denied transplant listing reported denying all marijuana-using patients or mandating abstinence before transplant listing. CONCLUSIONS: The majority of heart and lung transplant providers in our study sample supports the listing of patients who use medical marijuana for transplant after a period of abstinence. Communication and collaboration between the medical community and legislative groups about marijuana use in transplant candidates is needed to ensure the best patient outcomes with the use of scarce donor organs. PMID- 27413037 TI - Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial. AB - BACKGROUND: Heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Whether HFiEF is clinically distinct from HF with persistently reduced ejection fraction remains to be validated. METHODS AND RESULTS: Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a baseline left ventricular EF of <35% and a follow-up echocardiographic assessment of EF at 12 months. Of these, 321 (9.1%) patients who had a 12-month EF of >40% constituted the subgroup with HFiEF. EF improved from 28.7+/-5.6% to 46.5+/-5.6% in the subgroup with HFiEF and remained reduced (25.2+/-6.2% and 27.5+/-7.1%) in the subgroup with HF with reduced ejection fraction. The group with HFiEF had a less severe hemodynamic, biomarker, and neurohormonal profile, and it was treated with a more intense HF medication regimen. Subjects who had higher blood pressure and those treated with a beta blocker or randomized to valsartan had greater odds of being in the HFiEF group, whereas those with an ischemic pathogenesis, a more dilated left ventricle, and a detectable hs-troponin had lower odds of an improvement in EF. Recovery of the EF to >40% was associated with a better survival compared with persistently reduced EF. CONCLUSIONS: Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome, which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease, a less severe hemodynamic, biomarker, and neurohormonal profile, and who are treated with a more intense HF medication regimen. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336. PMID- 27413038 TI - Zooming in on the Microvasculature in Heart Failure With Preserved Ejection Fraction. PMID- 27413039 TI - Trends in Cardiovascular Health Metrics in Obese Adults: National Health and Nutrition Examination Survey (NHANES), 1988-2014. AB - BACKGROUND: No study has quantified trends in the prevalence of cardiovascular disease risk factors and cardiovascular health metrics among obese people in the United States in recent years. METHODS AND RESULTS: We examined the secular changes in cardiovascular health metrics and key cardiovascular disease risk factors among obese adults (aged >=20 years) in the United States. We included 18 626 obese adults (body mass index >=30) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Among those obese adults, there were decreases in mean systolic blood pressure, diastolic blood pressure, and total cholesterol levels and increases in mean high-density lipoprotein cholesterol levels and mean hemoglobin A1c levels. Prevalence of blood pressure health and lipid health remained stable during the period 1988-2014, whereas prevalence of blood glucose health decreased significantly during this period. Prevalence of freedom from cardiovascular disease risk factors remained stable at ~15% among the adult obese population during the period 1988-2014, whereas prevalence of presence of all 3 risk factors increased from 16.4% to 22.4% during this period, commensurate with a decline in those with 1 to 2 risk factors (from 69.6% to 62.4%). CONCLUSIONS: During the past 3 decades, blood pressure health and blood lipid health remained stable or improved, whereas blood glucose health deteriorated among adult obese population. This resulted in an overall decrease in cardiovascular health status among obese adults and greater risk of type 2 diabetes mellitus. The data argue for interventions targeted to those obese persons who are metabolically unhealthy to stem rising rates of diabetes mellitus. PMID- 27413040 TI - Obesity Is Associated With Progression of Atherosclerosis During Statin Treatment. AB - BACKGROUND: This study aimed to determine the relationship of statin therapy and cardiovascular risk factors to changes in atherosclerosis in the carotid artery. METHODS AND RESULTS: Carotid magnetic resonance imaging was used to evaluate 106 hyperlipidemic participants at baseline and after 12 months of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitor (statin) treatment. Multivariable logistic regression was used to determine factors associated with progression (change in carotid wall volume >0) or regression (change <=0) of carotid atherosclerosis. Computed tomography coronary calcium scores were obtained at baseline for all participants. The median age was 65 years (interquartile range 60-69 years), and 63% of the participants were male. Body mass index >30, elevated C-reactive protein, and hypertension were associated with increased carotid wall volume (obesity: odds ratio for progression 4.6, 95% CI 1.8-12.4, P<0.01; C-reactive protein: odds ratio for progression 2.56, 95% CI 1.17-5.73, P=0.02; hypertension: odds ratio 2.4, 95% CI 1.1-5.3, P<0.05). Higher statin dose was associated with regression of carotid wall volume (P<0.05). In multivariable analysis, obesity remained associated with progression (P<0.01), whereas statin use remained associated with regression (P<0.05). Change in atheroma volume in obese participants was +4.8% versus -4.2% in nonobese participants (P<0.05) despite greater low-density lipoprotein cholesterol reduction in obese participants. CONCLUSIONS: In a population with hyperlipidemia, obese patients showed atheroma progression despite optimized statin therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01212900. PMID- 27413041 TI - Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats. AB - BACKGROUND: We previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM. METHODS AND RESULTS: Male Sprague-Dawley rats (n=213) subjected to 10-minute ACA/CPR were randomized to 4 groups after return of spontaneous circulation (ROSC): normothermia control (NT); GBC; TTM; and TTM+GBC. Survival, neurodeficit scores, histological injury, as well as the expressions of SUR1 and TRPM4 were evaluated. The 7-day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM+GBC group. Rats that received either GBC, TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC. Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR1-TRPM4 heterodimers were both strongly upregulated after ACA/CPR and expressed in multiple types of brain cells, but partly suppressed by TTM. CONCLUSIONS: GBC is comparable to TTM in improving survival and neurological outcome after ACA/CPR. When GBC is given along with TTM, less histological injury tended to be achieved. PMID- 27413042 TI - Circulating N-Linked Glycoprotein Side-Chain Biomarker, Rosuvastatin Therapy, and Incident Cardiovascular Disease: An Analysis From the JUPITER Trial. AB - BACKGROUND: GlycA, a novel protein glycan biomarker of N-acetyl side chains of acute-phase proteins, was recently associated with incident cardiovascular disease (CVD) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. METHODS AND RESULTS: In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein (hsCRP) >=2 mg/L were randomized to rosuvastatin 20 mg/day or placebo. GlycA was quantified by nuclear magnetic resonance spectroscopy in 12 527 before randomization and 10 039 participants at 1 year. A total of 310 first primary CVD events occurred during maximum follow-up of 5.0 years (median, 1.9). GlycA changed minimally after 1 year on study treatment: 6.8% and 4.7% decrease in the rosuvastatin and placebo groups, respectively. Overall, baseline GlycA levels were associated with increased risk of CVD: multivariable-adjusted hazard ratio (HR) per SD increment, 1.20 (95% CI, 1.08-1.34; P=0.0006). After additionally adjusting for hsCRP, this was slightly attenuated (HR, 1.18; 95% CI, 1.04-1.35; P=0.01). On-treatment GlycA levels were also associated with CVD; corresponding multivariable-adjusted HRs per SD before and after additionally adjusting for hsCRP: 1.27 (95% CI, 1.13-1.42; P<0.0001) and 1.24 (95% CI, 1.07-1.44; P=0.004), respectively. Tests for heterogeneity by treatment arm were not significant (P for interaction, >0.20). CONCLUSION: In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP. CLINICAL TRIALS REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. PMID- 27413043 TI - Ischemic Stroke Risk After Acute Coronary Syndrome. AB - BACKGROUND: Prior studies show an increased risk of ischemic stroke (IS) after myocardial infarction; however, there is limited evidence on long-term risk and whether it is directly related to cardiac injury. We hypothesized that the risk of IS after acute coronary syndrome is significantly higher if there is evidence of cardiac injury, such as ST-segment elevation myocardial infarction (STEMI) or non-STEMI, than when there is no evidence of cardiac injury, such as in unstable angina. METHODS AND RESULTS: Administrative claims data were obtained from all emergency department encounters and hospitalizations at California's nonfederal acute care hospitals between 2008 and 2011. Patients with STEMI, non-STEMI, and unstable angina were identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. The primary outcome was IS during 2 years of follow-up. Unadjusted and adjusted Cox proportional hazards models were used to determine the association between acute coronary syndrome subtype and IS risk. We identified 73 059 patients with a diagnosis of STEMI (n=26 427), non-STEMI (n=39 833), or unstable angina (n=6819) during the study period. In the fully adjusted models that included potential confounders such as atrial fibrillation and congestive heart failure, the risk of IS was higher with STEMI (hazard ratio 4.17, 95% CI 3.00-5.83; P<0.001) and non-STEMI (hazard ratio 3.73, 95% CI 2.68-5.19, P<0.001) compared with unstable angina. CONCLUSIONS: Non STEMI and STEMI confer an equally increased risk of IS. Studies exploring IS mechanisms in cardiac patients are needed to improve and tailor stroke prevention strategies. PMID- 27413044 TI - Pigment Epithelium-Derived Factor (PEDF) Improves Ischemic Cardiac Functional Reserve Through Decreasing Hypoxic Cardiomyocyte Contractility Through PEDF Receptor (PEDF-R). AB - BACKGROUND: Pigment epithelium-derived factor (PEDF), which belongs to the noninhibitory serpin family, has shown the ability to stimulate several physiological processes, such as antiangiogenesis, anti-inflammation, and antioxidation. In the present study, the effects of PEDF on contractility and calcium handling of rat ventricular myocytes were investigated. METHODS AND RESULTS: Adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-lentivirus was delivered into the myocardium along and away from the infarction border to overexpress PEDF. Video edge detection was used to measure myocyte shortening in vitro. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator, Fura-2-acetoxymethyl ester. PEDF local overexpression enhanced cardiac functional reserve in AMI rats and reduced myocardial contracture bordering the infracted area. Exogenous PEDF treatment (10 nmol/L) caused a significant decrease in amplitudes of isoproterenol-stimulated myocyte shortening, Ca(2+) transients, and caffeine-evoked Ca(2+) transients in vitro. We then tested a potential role for PEDF receptor-mediated effects on upregulation of protein kinase C (PKC) and found evidence of signaling through the diacylglycerol/PKCalpha pathway. We also confirmed that pretreatment of cardiomyocytes with PEDF exhibited dephosphorylation of phospholamban at Ser(16), which could be attenuated with PKC inhibition. CONCLUSIONS: The results suggest that PEDF depresses myocyte contractility by suppressing phosphorylation of phospholamban and Ca(2+) transients in a PKCalpha-dependent manner through its receptor, PEDF receptor, therefore improving cardiac functional reserve during AMI. PMID- 27413045 TI - Particulate Matter and Hospital Admissions for Stroke in Beijing, China: Modification Effects by Ambient Temperature. AB - BACKGROUND: The impact of particulate matter (PM) on stroke may vary by particle size, stroke subtype, and patient characteristics and temperature. We examined the association of stroke admissions with PM in different subgroups in Beijing, China, during 2013-2014. METHODS AND RESULTS: A time-stratified case-crossover design was used to assess the relation between PM of different particle sizes and hospital admissions for ischemic and hemorrhagic stroke. Stratified analyses were performed by age, sex, and temperature. In total, there were 147 624 stroke admissions during the study period. In the whole-period analysis, both PM2.5 and PM10 were positively associated with ischemic stroke admissions on the day of hospital admission and negatively associated with ischemic stroke at lag2 and lag3 day. In warm days (>13.5 degrees C), the odds ratios of ischemic stroke admissions were 2.071 (95% CI 1.959-2.190), 1.470 (95% CI 1.391-1.554), and 1.590 (95% CI 1.493-1.694) per IQR increase in the same-day PM2.5 (82.0 MUg/m(3)), PM2.5-10 (36.6 MUg/m(3)), and PM10 (93.5 MUg/m(3)), respectively. For hemorrhagic stroke, the corresponding values were 1.941 (95% CI 1.658-2.273), 1.590 (95% CI 1.366-1.851), and 1.527 (95% CI 1.278-1.826). The positive associations were also observed in the other lag structures and were higher than in cold days (<=13.5 degrees C). CONCLUSIONS: This study suggests that the associations of PM2.5, PM2.5-10, and PM10 with stroke admissions differed across levels of temperature. Short-term exposure to PM2.5, PM2.5-10, and PM10 was positively associated with hospital admissions for ischemic and hemorrhagic stroke on warm days (>13.5 degrees C). PMID- 27413046 TI - Jatrophihabitans huperziae sp. nov., an endophytic actinobacterium isolated from surface-sterilized tissue of the medicinal plant Huperzia serrata (Thunb.). AB - A novel endophytic actinobacterium, designated strain CPCC 204076T, was isolated from surface-sterilized tissue of the medicinal plant Huperzia serrata (Thunb.) collected from Sichuan Province, south-west China. The taxonomic position of the isolate was investigated by a polyphasic approach. The strainwas aerobic, Gram stain-positive, non-motile, non-spore-forming and rod-shaped. Growth was observed at 10-37 degrees C, at pH 5.0-10.0 and with 0-3.0 % (w/v) NaCl. The polar lipid fraction consisted of diphosphatidylglycerol, a phospholipid, an aminolipid, a glycolipid, an aminophospholipid and phosphatidylinositol. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid and the peptidoglycan was of type A4gamma. The menaquinone system consisted of MK-9(H4) and MK-8(H4). The major cellular fatty acids (>10 %) were iso-C16 : 0 and anteiso C17 : 0. The genomic DNA G+C content of strain CPCC 204076T was found to be 71.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that CPCC 204076T belongs to the genus Jatrophihabitans with highest sequence similarity to Jatrophihabitans endophyticus DSM 45627T (96.5 %), Jatrophihabitans soli DSM 45908T (96.5 %) and Jatrophihabitans fulvus JCM 30448T (96.1 %), and much lower similarities (<95.0 %) to other available 16S rRNA gene sequences from validly described pure cultures. However, DNA-DNA hybridyzation values between strain CPCC 204076T and the three recognized Jatrophihabitans species were 31+/-3.1 % (J. endophyticus DSM 45627T), 33+/-2.9 % (J. soli DSM 45908T) and 37+/-1.7 % (J. fulvus JCM 30448T), which were all far below the recommended cut-off value of 70 %. The phenotypic and genomic characteristics distinctly indicated that strain CPCC 204076T represents a novel species of the genus Jatrophihabitans, for which the name Jatrophihabitans huperziae sp. nov. is proposed. The type strain is CPCC 204076T (I13A-01604) (=DSM 46866T=NBRC 110718T). PMID- 27413048 TI - On the Potential Origins of the High Stability of Reconstructed Ancestral Proteins. AB - Ancestral reconstruction provides instrumental insights regarding the biochemical and biophysical characteristics of past proteins. A striking observation relates to the remarkably high thermostability of reconstructed ancestors. The latter has been linked to high environmental temperatures in the Precambrian era, the era relating to most reconstructed proteins. We found that inferred ancestors of the serum paraoxonase (PON) enzyme family, including the mammalian ancestor, exhibit dramatically increased thermostabilities compared with the extant, human enzyme (up to 30 degrees C higher melting temperature). However, the environmental temperature at the time of emergence of mammals is presumed to be similar to the present one. Additionally, the mammalian PON ancestor has superior folding properties (kinetic stability)-unlike the extant mammalian PONs, it expresses in E. coli in a soluble and functional form, and at a high yield. We discuss two potential origins of this unexpectedly high stability. First, ancestral stability may be overestimated by a "consensus effect," whereby replacing amino acids that are rare in contemporary sequences with the amino acid most common in the family increases protein stability. Comparison to other reconstructed ancestors indicates that the consensus effect may bias some but not all reconstructions. Second, we note that high stability may relate to factors other than high environmental temperature such as oxidative stress or high radiation levels. Foremost, intrinsic factors such as high rates of genetic mutations and/or of transcriptional and translational errors, and less efficient protein quality control systems, may underlie the high kinetic and thermodynamic stability of past proteins. PMID- 27413047 TI - Conserved but Attenuated Parental Gene Expression in Allopolyploids: Constitutive Zinc Hyperaccumulation in the Allotetraploid Arabidopsis kamchatica. AB - Allopolyploidization combines parental genomes and often confers broader species distribution. However, little is known about parentally transmitted gene expression underlying quantitative traits following allopolyploidization because of the complexity of polyploid genomes. The allopolyploid species Arabidopsis kamchatica is a natural hybrid of the zinc hyperaccumulator Arabidopsis halleri and of the nonaccumulator Arabidopsis lyrata We found that A. kamchatica retained the ability to hyperaccumulate zinc from A. halleri and grows in soils with both low and high metal content. Hyperaccumulation of zinc by A. kamchatica was reduced to about half of A. halleri, but is 10-fold greater than A. lyrata Homeologs derived from A. halleri had significantly higher levels of expression of genes such as HEAVY METAL ATPASE4 (HMA4), METAL TRANSPORTER PROTEIN1 and other metal ion transporters than those derived from A. lyrata, which suggests cis regulatory differences. A. kamchatica has on average about half the expression of these genes compared with A. halleri due to fixed heterozygosity inherent in allopolyploids. Zinc treatment significantly changed the ratios of expression of 1% of homeologous pairs, including genes putatively involved in metal homeostasis. Resequencing data showed a significant reduction in genetic diversity over a large genomic region (290 kb) surrounding the HMA4 locus derived from the A. halleri parent compared with the syntenic A. lyrata-derived region, which suggests different evolutionary histories. We also estimated that three A. halleri-derived HMA4 copies are present in A. kamchatica Our findings support a transcriptomic model in which environment-related transcriptional patterns of both parents are conserved but attenuated in the allopolyploids. PMID- 27413051 TI - RETRACTED: Adjusting for illness severity shows there is no difference in patient mortality at weekends or weekdays for emergency medical admissions. PMID- 27413049 TI - Reverse Transcription Errors and RNA-DNA Differences at Short Tandem Repeats. AB - Transcript variation has important implications for organismal function in health and disease. Most transcriptome studies focus on assessing variation in gene expression levels and isoform representation. Variation at the level of transcript sequence is caused by RNA editing and transcription errors, and leads to nongenetically encoded transcript variants, or RNA-DNA differences (RDDs). Such variation has been understudied, in part because its detection is obscured by reverse transcription (RT) and sequencing errors. It has only been evaluated for intertranscript base substitution differences. Here, we investigated transcript sequence variation for short tandem repeats (STRs). We developed the first maximum-likelihood estimator (MLE) to infer RT error and RDD rates, taking next generation sequencing error rates into account. Using the MLE, we empirically evaluated RT error and RDD rates for STRs in a large-scale DNA and RNA replicated sequencing experiment conducted in a primate species. The RT error rates increased exponentially with STR length and were biased toward expansions. The RDD rates were approximately 1 order of magnitude lower than the RT error rates. The RT error rates estimated with the MLE from a primate data set were concordant with those estimated with an independent method, barcoded RNA sequencing, from a Caenorhabditis elegans data set. Our results have important implications for medical genomics, as STR allelic variation is associated with >40 diseases. STR nonallelic transcript variation can also contribute to disease phenotype. The MLE and empirical rates presented here can be used to evaluate the probability of disease-associated transcripts arising due to RDD. PMID- 27413050 TI - Lokiarchaeota Marks the Transition between the Archaeal and Eukaryotic Selenocysteine Encoding Systems. AB - Selenocysteine (Sec) is the 21st amino acid in the genetic code, inserted in response to UGA codons with the help of RNA structures, the SEC Insertion Sequence (SECIS) elements. The three domains of life feature distinct strategies for Sec insertion in proteins and its utilization. While bacteria and archaea possess similar sets of selenoproteins, Sec biosynthesis is more similar among archaea and eukaryotes. However, SECIS elements are completely different in the three domains of life. Here, we analyze the archaeon Lokiarchaeota that resolves the relationships among Sec insertion systems. This organism has selenoproteins representing five protein families, three of which have multiple Sec residues. Remarkably, these archaeal selenoprotein genes possess conserved RNA structures that strongly resemble the eukaryotic SECIS element, including key eukaryotic protein-binding sites. These structures also share similarity with the SECIS element in archaeal selenoprotein VhuD, suggesting a relation of direct descent. These results identify Lokiarchaeota as an intermediate form between the archaeal and eukaryotic Sec-encoding systems and clarify the evolution of the Sec insertion system. PMID- 27413053 TI - Lewinella aquimaris sp. nov., isolated from seawater. AB - A Gram-staining-negative, oval- or rod-shaped, non-motile bacterial strain, designated HDW-36T, was isolated from seawater off the Korean peninsula. Strain HDW-36T was found to grow optimally at pH 7.0-8.0, at 25 degrees C and in the presence of 2-3 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain HDW-36T falls within the clade comprising thespecies of the genus Lewinella, clustering with the type strains of Lewinella xylanilytica and Lewinella marina, with which it exhibited 95.9 % and 95.2 % sequence similarity values, respectively. The 16S rRNA gene sequence similarity values between strain HDW-36T and type strains of other species of the genus Lewinella were 88.4-92.8 %. Strain HDW-36T was found to contain MK-7 as the predominant menaquinone and summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c), iso-C15 : 0 and C16 : 0 as the major fatty acids. The major polar lipids were identified as phosphatidylethanolamine and an unidentified lipid. The DNA G+C content of strain HDW-36T was determined to be 60.9 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness, demonstrate that strain HDW-36T is distinguishable from other species of the genus Lewinella. On the basis of the data presented, strain HDW-36T is considered to represent a novel species, for which the name Lewinella aquimaris sp. nov. is proposed. The type strain of Lewinella aquimaris is HDW-36T (=KCTC 42719T=CECT 8901T). PMID- 27413052 TI - European Society of Cardiology-Recommended Coronary Artery Disease Consortium Pretest Probability Scores More Accurately Predict Obstructive Coronary Disease and Cardiovascular Events Than the Diamond and Forrester Score: The Partners Registry. AB - BACKGROUND: The most appropriate score for evaluating the pretest probability of obstructive coronary artery disease (CAD) is unknown. We sought to compare the Diamond-Forrester (DF) score with the 2 CAD consortium scores recently recommended by the European Society of Cardiology. METHODS: We included 2274 consecutive patients (age, 56+/-13 years; 57% male) without prior CAD referred for coronary computed tomographic angiography. Computed tomographic angiography findings were used to determine the presence or absence of obstructive CAD (>=50% stenosis). We compared the DF score with the 2 CAD consortium scores with respect to their ability to predict obstructive CAD and the potential implications of these scores on the downstream use of testing for CAD, as recommended by current guidelines. RESULTS: The DF score did not satisfactorily fit the data and resulted in a significant overestimation of the prevalence of obstructive CAD (P<0.001); the CAD consortium basic score had no significant lack of fitness; and the CAD consortium clinical provided adequate goodness of fit (P=0.39). The DF score had a lower discrimination for obstructive CAD, with an area under the receiver-operating characteristics curve of 0.713 versus 0.752 and 0.791 for the CAD consortium models (P<0.001 for both). Consequently, the use of the DF score was associated with fewer individuals being categorized as requiring no additional testing (8.3%) compared with the CAD consortium models (24.6% and 30.0%; P<0.001). The proportion of individuals with a high pretest probability was 18% with the DF and only 1.1% with the CAD consortium scores (P<0.001) CONCLUSIONS: Among contemporary patients referred for noninvasive testing, the DF risk score overestimates the risk of obstructive CAD. On the other hand, the CAD consortium scores offered improved goodness of fit and discrimination; thus, their use could decrease the need for noninvasive or invasive testing while increasing the yield of such tests. PMID- 27413054 TI - Drugs That Affect the Resting Heart Rate. PMID- 27413055 TI - Preprocedural Albumin Levels and Risk of In-Stent Restenosis After Coronary Stenting With Bare-Metal Stent. PMID- 27413056 TI - Endocan in Hypertension and Cardiovascular Diseases. PMID- 27413057 TI - Endocan: Endothelial Dysfunction, Inflammation, or Both? PMID- 27413058 TI - An Assessment of Levels of Safety in Psychiatric Units. AB - OBJECTIVES: This article aims to understand the incident patterns in relation to different types of spaces within a psychiatric unit, which are discussed using the five levels of safety framework. BACKGROUND: Implementing measures to improve patient safety is essential particularly in a psychiatric hospital, where limited research has been conducted on inpatient safety. Therefore, this article aims to understand the incident patterns from the lens of the five levels of safety framework, which categorizes spaces according to the level of patient supervision in psychiatric facilities, as follows: service areas, corridors, dayrooms, patient rooms and bathrooms, seclusions and admissions. METHODS: In an 81-bed psychiatric hospital, this mixed-method study drew 7 years of incident reports and caregivers' perceptions gathered through focus groups. Incident reports on physical safety were analyzed based on the five levels of safety framework ( N = 1,316). Focus groups ( n = 9) explored the caregivers' viewpoints on patient safety and five categories of spaces. RESULTS: Overall findings support the five levels of safety pattern, confirming that most incidents occurred in patient rooms and bathrooms; moreover, relatively fewer incidents happened in dayrooms and corridors. Elopements are higher in hallways and dayrooms. Suicide is most common in patient rooms and bathrooms, and violence is more frequent in dayrooms. Focus groups results yielded insightful recommendations. CONCLUSIONS: Levels of safety framework can be adapted to seven categories where seclusion room and admission area would be two of the spaces with least incidents. PMID- 27413059 TI - Delivering Rural Health in a Changing Health Model: A Qualitative Study Involving Four Hospitals. AB - OBJECTIVES: An exploratory examination of rural hospital staff experiences to determine whether the physical state of rural healthcare facilities influence the healthcare experience and perception of care quality. BACKGROUND: Rural hospitals have served as the backbone of rural communities in the United States. Over time, these facilities have witnessed enhanced expectations, expanding their scope of operations from acute care to diversified services through linked provider networks and disaster management. Simultaneously, financial challenges, increasing emphasis on safety and quality, and the Affordable Care Act have introduced new challenges for rural hospitals. Currently, there is little empirical knowledge in this domain from a facility perspective. METHODS: An exploratory qualitative study was conducted, involving semistructured interviews of upper and mid-level administrators in four rural hospitals located in West Texas. All questions attempted to obtain the subject's knowledge, ideas, and opinions concerning the physical design of the hospitals and the hospital experience. RESULTS: According to data on staff experiences, two classes of factors surfaced as potential influencers of hospital experience and care quality: (1) care configuration and (2) outdated building. Care configuration pertains to positioning facilities designed with inpatient care focus to a market expanding in outpatient services. Outdated buildings affect several issue including perceived provider quality and spatial accommodations for safe/efficient care and thereby also affecting the healthcare experience. CONCLUSIONS: Physical infrastructure of rural hospitals may have important and meaningful implications for population health performance in rural America. PMID- 27413060 TI - Cigarette sales to minors via the internet: how the story has changed in the wake of federal regulation. AB - OBJECTIVE: To assess how easily minors can purchase cigarettes online and online cigarette vendors' compliance with federal age/ID verification and shipping regulations, North Carolina's 2013 tobacco age verification law, and federal prohibitions on the sale of non-menthol flavoured cigarettes or those labelled or advertised as 'light'. METHODS: In early 2014, 10 minors aged 14-17 attempted to purchase cigarettes by credit card and electronic check from 68 popular internet vendors. RESULTS: Minors received cigarettes from 32.4% of purchase attempts, all delivered by the US Postal Service (USPS) from overseas sellers. None failed due to age/ID verification. All failures were due to payment processing problems. USPS left 63.6% of delivered orders at the door with the remainder handed to minors with no age verification. 70.6% of vendors advertised light cigarettes and 60.3% flavoured, with 23.5% and 11.8%, respectively, delivered to the teens. Study credit cards were exposed to an estimated $7000 of fraudulent charges. CONCLUSIONS: Despite years of regulations restricting internet cigarette sales, poor vendor compliance and lack of shipper and federal enforcement leaves minors still able to obtain cigarettes (including 'light' and flavoured) online. The internet cigarette marketplace has shifted overseas, exposing buyers to widespread credit card fraud. Federal agencies should rigorously enforce existing internet cigarette sales laws to prevent illegal shipments from reaching US consumers, shut down non-compliant and fraudulent websites, and stop the theft and fraudulent use of credit card information provided online. Future studies should assess whether these agencies begin adequately enforcing the existing laws. PMID- 27413061 TI - Setting the agenda for a healthy retail environment: content analysis of US newspaper coverage of tobacco control policies affecting the point of sale, 2007 2014. AB - BACKGROUND: Tobacco control policies affecting the point of sale (POS) are an emerging intervention, yet POS-related news media content has not been studied. PURPOSE: We describe news coverage of POS tobacco control efforts and assess relationships between article characteristics, including policy domains, frames, sources, localisation and evidence present, and slant towards tobacco control efforts. METHODS: High circulation state (n=268) and national (n=5) newspapers comprised the sampling frame. We retrieved 917 relevant POS-focused articles in newspapers from 1 January 2007 to 31 December 2014. 5 raters screened and coded articles, 10% of articles were double coded, and mean inter-rater reliability (IRR) was 0.74. RESULTS: POS coverage emphasised tobacco retailer licensing (49.1% of articles) and the most common frame present was regulation (71.3%). Government officials (52.3%), followed by tobacco retailers (39.6%), were the most frequent sources. Half of articles (51.3%) had a mixed, neutral or antitobacco control slant. Articles presenting a health frame, a greater number of protobacco control sources, and statistical evidence were significantly more likely to also have a protobacco control slant. Articles presenting a political/rights or regulation frame, a greater number of antitobacco control sources, or government, tobacco industry, tobacco retailers, or tobacco users as sources were significantly less likely to also have a protobacco control slant. CONCLUSIONS: Stories that feature procontrol sources, research evidence and a health frame also tend to support tobacco control objectives. Future research should investigate how to use data, stories and localisation to encourage a protobacco control slant, and should test relationships between content characteristics and policy progression. PMID- 27413062 TI - Smoking reduced in urban restaurants: the effect of Beijing Smoking Control Regulation. AB - OBJECTIVE: To evaluate the effectiveness of Beijing Smoking Control Regulation, occurrence of smoking in restaurants was compared before and after the law took effect. METHODS: A cohort study design was used in a randomly selected sample of 176 restaurants in two districts of Beijing. Undercover visits were paid by investigators to the same restaurants at lunch or dinner time 5 months before the law took effect and 1-month after. The occurrence of smoking and presence of no smoking signs were observed. RESULTS: Much less smoking was observed (14.8%) in restaurants compared to that before the law took effect (40.3%). The drop in smoking occurrence was more evident in open dining areas (from 32.4% to 5.1%) compared to the men's restrooms of the restaurants (23.8% to 18.8%). No intervention from restaurant staff was observed whenever smoking occurred. Posting of no-smoking signage increased considerably after the law came into effect (from 52.6% to 82.4%), but very few no-smoking signs included the symptom hotline number (38.5%) or the amount of penalty (5.6%). CONCLUSIONS: The Beijing Smoking Control Regulation achieved one of its intended goals of reducing smoking occurrences in restaurants, but further effort of strengthening implementation is still needed and should focus on boosting compliance with no-smoking sign requirements, reducing smoking in restrooms of the restaurants and mobilising the restaurant staff to intervene in case of violations. PMID- 27413063 TI - Transradial/Transbrachial Carotid Artery Stenting With Proximal or Distal Protection: A Promising Technique for the Reduction of Vascular Complications and Stroke. PMID- 27413064 TI - Re: Proximal Uncovered Stent Disconnections With the Standard and Low-Profile Zenith AAA Stent-Grafts. PMID- 27413065 TI - Intravascular Ultrasound Is an Effective Tool for Predicting Histopathology Confirmed Evidence of Adventitial Injury Following Directional Atherectomy for the Treatment of Peripheral Artery Disease. PMID- 27413066 TI - In Memoriam. PMID- 27413067 TI - A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection. AB - Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd. PMID- 27413068 TI - Animal Models for Salmonellosis: Applications in Vaccine Research. AB - Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development. PMID- 27413069 TI - Salmonella Serogroup C: Current Status of Vaccines and Why They Are Needed. AB - Nontyphoidal Salmonella (NTS; i.e., Salmonella enterica organisms that do not cause typhoid or paratyphoid) are responsible for 94 million infections and 155,000 deaths worldwide annually, 86% of which are estimated to be foodborne. Although more than 50 serogroups and 2,600 serovars have been described, not all Salmonella serovars cause disease in humans and animals. Efforts are being made to develop NTS vaccines, with most approaches eliciting protection against serovars Typhimurium and Enteritidis (serogroups B [O:4] and D [O:9], respectively), as they are widely considered the most prevalent. Here, we show that serogroup C (O:6,7, O:6,8, or O:8 epitopes) is the most common serogroup in the United States, and the prevalence of serovars from this serogroup has been increasing in Europe and the United States over the last decade. They are also the most commonly isolated serovars from healthy cattle and poultry, indicating the underlying importance of surveillance in animals. Four out of the 10 most lethal serovars in the United States are serogroup C, and reports from African countries suggest that strains within this serogroup are highly antibiotic resistant. Serogroup C consists of highly diverse organisms among which 37 serovars account for the majority of human cases, compared to 17 and 11 serovars for serogroups B and D, respectively. Despite these concerning data, no human vaccines targeting serogroup C NTS are available, and animal vaccines are in limited use. Here, we describe the underestimated burden represented by serogroup C NTS, as well as a discussion of vaccines that target these pathogens. PMID- 27413070 TI - Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial. AB - This trial was conducted to explore the safety of recombinant fusion protein ESAT6-CFP10 as a skin test reagent for the diagnosis of Mycobacterium tuberculosis infection. Twenty-four healthy adult volunteers were recruited and randomized into four groups (groups A to D) to study four increasing doses of ESAT6-CFP10. All subjects in each dose group received an intradermal injection of reagent (0.1 ml) via the Mantoux technique. Then, the vital signs of all subjects were monitored, and skin reactions around injection sites and adverse events were recorded at different detection time points after the skin test. No serious adverse events were observed in this study. A total of 3 subjects had unexpected events. One subject in group A developed subcutaneous hemorrhage 24 h after the skin test, one subject in group B was found with red spots 15 min after the skin test, and another subject in group A showed abnormity during a chest X-ray after the skin test without affecting her health. One of three adverse events (red spots) was probably related to the recombinant ESAT6-CFP10 reagent. A single dose of 1, 5, 10, or 20 MUg/ml of recombinant ESAT6-CFP10 as a skin test reagent for M. tuberculosis infection diagnosis is well tolerated and safe in China. (This study has been registered at ClinicalTrials.gov under registration no. NCT01999231.). PMID- 27413073 TI - Correction. PMID- 27413074 TI - RORgammat Expression and Lymphoid Neogenesis in the Brain of Patients with Secondary Progressive Multiple Sclerosis. AB - Ectopic B-cell follicle-like structures (ELS) are found in the meninges of patients with secondary progressive multiple sclerosis (SPMS). Because cells expressing the transcriptional regulator retinoic acid receptor-related orphan receptor-gammat (RORgammat) and producing interleukin 17 (IL17), e.g. T helper 17 cells and lymphoid tissue inducer (LTi) cells, have been implicated in the formation of ELS, we studied RORgammat and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS. By immunohistochemistry, small numbers of RORgammat-positive cells were detected in the meninges of 6 of 12 SPMS cases analyzed. RORgammat-positive cells were localized in B-cell follicles or aggregates and nearby diffuse meningeal infiltrates, and predominantly co-expressed CD3. Only a few RORgammat positive, CD3-negative cells were observed, suggesting the presence of group 3 innate lymphoid cells, which comprise the LTi cell subset. Some IL17-positive cells, co-expressing in part RORgammat and predominantly CD3, were found in meningeal B-cell follicles from 4 SPMS cases. Rare RORgammat-positive and IL17 positive cells were detected in white matter. Gene expression analysis of laser dissected meningeal infiltrates and white matter lesions confirmed low frequencies and virtual absence of RORgammat and IL17 signals, respectively. Thus, there is selective migration or survival of RORgammat-positive cells in MS patient meninges and an association of these cells with ELS. PMID- 27413071 TI - Nebulized Fentanyl in Acute Pain: A Systematic Review. AB - OBJECTIVE: To provide a systematic review of the current role of nebulized fentanyl in acute pain and potentially other conditions. DATA SOURCES: A MEDLINE literature search inclusive of the dates 1946 to May 2016 was performed using the following search terms: fentanyl and administration, inhaled Excerpta Medica was searched from 1980 to May 2016 using the following search terms: exp fentanyl/inhalation drug administration Additionally, Web of Science was searched using the terms fentanyl and pain inclusive of 1945 to May 2016. STUDY SELECTION AND DATA EXTRACTION: We utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to select English language, human primary literature, review articles, and supporting data assessing the efficacy of nebulized fentanyl in acute pain. DATA SYNTHESIS: Seven clinical trials have demonstrated no difference in efficacy between nebulized fentanyl and intravenous (IV) opioids. Few adverse effects were reported; however, the trials were of short duration. Nebulized fentanyl appeared to be a rapid-acting analgesic that does not require IV access. CONCLUSION: Evidence suggests that nebulized fentanyl is as effective as IV opioids in the treatment of acute pain, with relatively few adverse effects. However, questions remain about the extemporaneous preparation of fentanyl nebulized solution, the variability in nebulization devices, and ensuring consistent drug delivery to distal airways in the clinical setting. The abuse potential of nebulized fentanyl should also be considered. PMID- 27413075 TI - FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non-Small Cell Lung Cancer Following Crizotinib. AB - On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28-49] and 44% (95% CI, 36-53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46 74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit-risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171-6. (c)2016 AACR. PMID- 27413077 TI - Hemolysis Interference: Are Laboratories Getting the Information They Need? PMID- 27413076 TI - Premature T Cell Senescence in Pediatric CKD. AB - An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+ T cells, reduction in the proportion of naive T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation. PMID- 27413079 TI - Sustaining Gains Made in Voluntary Medical Male Circumcision. PMID- 27413080 TI - Early Infant Male Circumcision in Cameroon and Senegal: Demand, Service Provision, and Cultural Context. AB - BACKGROUND: Male circumcision is almost universal in North and West Africa, and practiced for various reasons. Yet there is little documentation on service delivery, clinical procedures, policies, and programmatic strategies. The United Nations Children's Fund (UNICEF) commissioned country program reviews in 2014 to shed light on the delivery of male circumcision services for infants in Cameroon and Senegal. METHODS: We conducted a policy desk review, key informant interviews, and focus group discussions at health centers and in communities. Between December 2014 and January 2015, we conducted 21 key informant interviews (13 with regional and district officers, 5 with national officers, and 3 with UNICEF officials) and 36 focus group discussions (6 with men, 6 with women, 12 with adolescent boys, and 12 with service providers). Some of the men and women were parents of the adolescents who participated in the focus group discussions. In the French-speaking areas, the focus group discussions were conducted in French through an accredited translator, audio recorded, and transcribed into English. RESULTS: All of the facilities we visited in Cameroon and Senegal offer medical male circumcision, with 10 out of 12 performing early infant male circumcision (EIMC) routinely. Neither country has policies, guidelines, or strategies for EIMC. The procedure is done mainly by untrained service providers, with some providers using modern circumcision devices. There are no key messages on EIMC for families; the increasing demand for EIMC is led by the community. CONCLUSION: Despite the absence of national policies and strategies, EIMC is routinely offered at all levels of the health care system in Cameroon and Senegal, mainly by untrained service providers. Improving circumcision services will require guidelines for EIMC and improvements in training, equipment, supply chains, recordkeeping, and demand creation. PMID- 27413081 TI - Bringing Early Infant Male Circumcision Information Home to the Family: Demographic Characteristics and Perspectives of Clients in a Pilot Project in Tanzania. AB - Iringa region of Tanzania has had great success reaching targets for voluntary medical male circumcision (VMMC). Looking to sustain high coverage of male circumcision, the government introduced a pilot project to offer early infant male circumcision (EIMC) in Iringa in 2013. From April 2013 to December 2014, a total of 2,084 male infants were circumcised in 8 health facilities in the region, representing 16.4% of all male infants born in those facilities. Most circumcisions took place 7 days or more after birth. The procedure proved safe, with only 3 mild and 3 moderate adverse events (0.4% overall adverse event rate). Overall, 93% of infants were brought back for a second-day visit and 71% for a seventh-day visit. These percentages varied significantly by urban and rural residence (97.4% urban versus 84.6% rural for day 2 visit; 82.2% urban versus 49.9% rural for day 7 visit). Mothers were more likely than fathers to have received information about EIMC. However, fathers tended to be key decision makers regarding circumcision of their sons. This suggests the importance of addressing fathers with behavioral change communication about EIMC. Successes in scaling up VMMC services in Iringa did not translate into immediate acceptability of EIMC. EIMC programs will require targeted investments in demand creation to expand and thrive in traditionally non-circumcising settings such as Iringa. PMID- 27413082 TI - Long-Term Investment for Infants: Keys to a Successful Early Infant Male Circumcision Program for HIV Prevention and Overall Child Health. PMID- 27413083 TI - Safety, Acceptability, and Feasibility of Early Infant Male Circumcision Conducted by Nurse-Midwives Using the AccuCirc Device: Results of a Field Study in Zimbabwe. AB - BACKGROUND: For prevention of HIV, early infant male circumcision (EIMC) needs to be scaled up in countries with high HIV prevalence. Routine EIMC will maintain the HIV prevention gains anticipated from current adult male circumcision initiatives. We present here the results of a field study of EIMC conducted in Zimbabwe. METHODS: The study was observational and based on the World Health Organization (WHO) framework for clinical evaluation of male circumcision devices. We recruited parents of newborn male infants between August 2013 and July 2014 from 2 clinics. Nurse-midwives used the AccuCirc device to circumcise eligible infants. We followed participants for 14 days after EIMC. Outcome measures were EIMC safety, acceptability, and feasibility. RESULTS: We enrolled 500 male infants in the field study (uptake 11%). The infants were circumcised between 6 and 60 days postpartum. The procedure took a median of 17 minutes (interquartile range of 5 to 18 minutes). Mothers' knowledge of male circumcision was extensive. Of the 498 mothers who completed the study questionnaire, 91% knew that male circumcision decreases the risk of HIV acquisition, and 83% correctly stated that this prevention is partial. Asked about their community's perception of EIMC, 40% felt that EIMC will likely be viewed positively in their community; 13% said negatively; and 47% said the perception could be both ways. We observed 7 moderate or severe adverse events (1.4%; 95% confidence interval, 0.4% to 2.4%). All resolved without lasting effects. Nearly all mothers (99%) reported great satisfaction with the outcome, would recommend EIMC to other parents, and would circumcise their next sons. CONCLUSION: This first field study in sub Saharan Africa of the AccuCirc device for EIMC demonstrated that EIMC conducted by nurse-midwives with this device is safe, feasible, and acceptable to parents. PMID- 27413084 TI - Perspectives of Parents and Health Care Workers on Early Infant Male Circumcision Conducted Using Devices: Qualitative Findings From Harare, Zimbabwe. AB - BACKGROUND: The World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommend early infant male circumcision (EIMC) for prevention of HIV. Here, we present findings from a qualitative study in Zimbabwe that assessed parental and health care workers' perspectives of EIMC conducted using devices. METHODS: This qualitative study was nested within a trial of EIMC devices. Between January and May 2013, we held 4 focus group discussions (FGDs) and 12 in depth interviews with parents and 12 in-depth interviews with clinicians (7 trial clinicians and 5 non-trial clinicians). We also conducted 95 short telephone interviews with parents who had arranged to bring their sons for EIMC but then defaulted. RESULTS: Parents who had adopted EIMC spoke of their initial anxieties about the procedure. Additionally, they commented on both the procedure and outcome. Parents who decided against EIMC cited fear of harm, specifically the infant's death, penile injury, and excessive pain. Misperceptions about male circumcision in general and EIMC specifically were a significant barrier to EIMC adoption and were prevalent among health care workers as well as parents. In particular, the findings suggest strong parental concerns about the fate of the discarded foreskin. Parents who chose EIMC for their newborn sons felt that the procedure was safe and expressed satisfaction with the outcome. For their part, health care workers largely thought that EIMC was safe and that the outcome was aesthetically pleasing. They also felt that it would be feasible to offer wide scale EIMC for HIV prevention in the public sector; they recommended strategies to increase EIMC uptake, in addition to highlighting a few concerns. CONCLUSIONS: The qualitative study enables us to better understand parental and health care workers' perspectives of EIMC conducted using devices, especially their perspectives on EIMC safety, feasibility, acceptability, and barriers. These findings will be used to design demand-generation activities that support wider adoption of EIMC. PMID- 27413085 TI - Comparative Cost of Early Infant Male Circumcision by Nurse-Midwives and Doctors in Zimbabwe. AB - BACKGROUND: The 14 countries that are scaling up voluntary male medical circumcision (VMMC) for HIV prevention are also considering early infant male circumcision (EIMC) to ensure longer-term reductions in HIV incidence. The cost of implementing EIMC is an important factor in scale-up decisions. We conducted a comparative cost analysis of EIMC performed by nurse-midwives and doctors using the AccuCirc device in Zimbabwe. METHODS: Between August 2013 and July 2014, nurse-midwives performed EIMC on 500 male infants using AccuCirc in a field trial. We analyzed the overall unit cost and identified key cost drivers of EIMC performed by nurse-midwives and compared these with costing data previously collected during a randomized noninferiority comparison trial of 2 devices (AccuCirc and the Mogen clamp) in which doctors performed EIMC. We assessed direct costs (consumable and nonconsumable supplies, device, personnel, associated staff training, and waste management costs) and indirect costs (capital and support personnel costs). We performed one-way sensitivity analyses to assess cost changes when we varied key component costs. RESULTS: The unit costs of EIMC performed by nurse-midwives and doctors in vertical programs were US$38.87 and US$49.77, respectively. Key cost drivers of EIMC were consumable supplies, personnel costs, and the device price. In this cost analysis, major cost drivers that explained the differences between EIMC performed by nurse midwives and doctors were personnel and training costs, both of which were lower for nurse-midwives. CONCLUSIONS: EIMC unit costs were lower when performed by nurse-midwives compared with doctors. To minimize costs, countries planning to scale up EIMC should consider using nurse-midwives, who are in greater supply than doctors and are the main providers at the primary health care level, where most infants are born. PMID- 27413086 TI - Scaling Up Early Infant Male Circumcision: Lessons From the Kingdom of Swaziland. AB - BACKGROUND: The government of the Kingdom of Swaziland recognizes that it must urgently scale up HIV prevention interventions, such as voluntary medical male circumcision (VMMC). Swaziland has adopted a 2-phase approach to male circumcision scale-up. The catch-up phase prioritizes VMMC services for adolescents and adults, while the sustainability phase involves the establishment of early infant male circumcision (EIMC). Swaziland does not have a modern-day tradition of circumcision, and the VMMC program has met with client demand challenges. However, since the launch of the EIMC program in 2010, Swaziland now leads the Eastern and Southern Africa region in the scale-up of EIMC. Here we review Swaziland's program and its successes and challenges. METHODS: From February to May 2014, we collected data while preparing Swaziland's "Male Circumcision Strategic and Operational Plan for HIV Prevention 2014-2018." We conducted structured stakeholder focus group discussions and in-depth interviews, and we collected EIMC service delivery data from an implementing partner responsible for VMMC and EIMC service delivery. Data were summarized in consolidated narratives. RESULTS: Between 2010 and 2014, trained providers performed more than 5,000 EIMCs in 11 health care facilities in Swaziland, and they reported no moderate or severe adverse events. According to a broad group of EIMC program stakeholders, an EIMC program needs robust support from facility, regional, and national leadership, both within and outside of HIV prevention coordination bodies, to promote institutionalization and ownership. Providers and health care managers in 3 of Swaziland's 4 regional hospitals suggest that when EIMC is introduced into reproductive, maternal, newborn, and child health platforms, dedicated staff attention can help ensure that EIMC is performed amid competing priorities. Creating informed demand from communities also supports EIMC as a service delivery priority. Formative research shows that EIMC programs should address the fears and anxieties of parents so that they, especially fathers, understand the health benefits of EIMC before the birth of their babies. CONCLUSION: The vast majority of public-sector facilities in Swaziland are led by nurses, and nurses and midwives have borne the brunt of caring for patients with HIV/AIDS in Swaziland. Like prevention of mother-to-child transmission, EIMC provides an opportunity for nurses and midwives to stand at the forefront of HIV prevention efforts. Rapid scale-up of VMMC and EIMC in Swaziland has the potential to avert more than 56,000 HIV infections and save US$370 million in the next 20 years. PMID- 27413087 TI - Scale-Up of Early Infant Male Circumcision Services for HIV Prevention in Lesotho: A Review of Facilitating Factors and Challenges. AB - BACKGROUND: The World Health Organization and the Joint United Nations Programme on HIV/AIDS recommend early infant male circumcision (EIMC) as a component of male circumcision programs in countries with high HIV prevalence and low circumcision rates. Lesotho began incorporating EIMC into routine maternal, newborn, and child health (MNCH) services in 2013 with funding from the United States Agency for International Development and United Nations Children's Fund. This presented unique challenges: Lesotho had no previous experience with EIMC and cultural traditions link removal of the foreskin to rites of passage. This process evaluation provides an overview of EIMC implementation. METHODOLOGY: The Lesotho Ministry of Health and Jhpiego conducted a baseline assessment before service implementation. Baseline information from an initial assessment was used to develop and implement an EIMC program that had a pilot and a scale-up phase. Key program activities such as staff training, quality assurance, and demand creation were included at the program design phase. Facilitating factors and challenges were identified from a review of information collected during the baseline assessment as well as the pilot. RESULTS: Between September 2013 and March 2015, 592 infants were circumcised at 9 sites: 165 (28%) between 1 day and 6 days after birth; 196 (33%) between 7 and 30 days, and 231 (39%) between 31 and 60 days. Facilitating factors included strong support from the Ministry of Health, collaboration with stakeholders, and donor funding. Providers were enthusiastic about the opportunity to offer new services and receive training. Challenges included gaining consent from family members other than mothers, and parents' concern about pain and complications. The EIMC program also had to manage providers' expectations of compensation because overtime was paid to providers who took part in adult circumcision programming but not for EIMC. Limited human resources, including authorization only for doctors to perform EIMC, impeded provision of services. CONCLUSION: Despite communication, compensation, and task-shifting challenges, integrating EIMC services with MNCH services could be a sustainable model for EIMC service delivery in Lesotho. PMID- 27413089 TI - Experiencing External Workplace Violence: Differences in Indicators Between Three Types of Emergency Responders. AB - Police officers, firefighters, and emergency medical workers are at a relatively high risk of experiencing external workplace violence (EWPV), that is, violence initiated by people outside the organization. Based on criminal opportunities theories, the aim of this research was to study to what extent socio-demographic and work characteristics are related to experiencing EWPV. In addition, the aim was to explore how these relations differ between the three types of emergency responders. Data from a workplace violence survey of the Ministry of the Interior and Kingdom Relations of the Netherlands was used, from which emergency medical workers ( n = 264), firefighters ( n = 255), and police officers ( n = 296) were selected. Results indicated that police officers experienced most and firefighters experienced least EWPV. Younger professionals and professionals who have more frequent and risky contact experienced more EWPV. The expectations that males and those with less skills or experience to avoid EWPV experience more EWPV were not convincingly supported. The relationships between characteristics and EWPV, and the explanatory power of the models, differed between types of emergency responders. The studied characteristics best explained variations in EWPV of police officers, and therefore prevention of EWPV by addressing these characteristics will be most successful for police officers. The prediction of EWPV should be improved, for example, by studying the relationship with "attractiveness" or "vulnerability" of the possible victim, such as psychological characteristics of professionals. The study showed that research about indicators and prevention of EWPV should be aimed at separate professions. PMID- 27413088 TI - Scaling Up and Sustaining Voluntary Medical Male Circumcision: Maintaining HIV Prevention Benefits. PMID- 27413090 TI - Women's Drinking Decisions in Heterosocial Situations: Development and Validation of Scenarios to Assess Influence of Attraction and Risk-Awareness. AB - These three related studies created a set of ecologically valid scenarios for assessing relative associations of both attraction and sexual coercion risk recognition in college women's heterosocial situational drinking decisions. The first study constructed nine scenarios using input from heterosexual drinking women in the age cohort (18-30) most likely to experience alcohol-related sexual coercion. In the second study, 50 female undergraduates (ages 18-25) assessed the salience of three important dimensions (attraction, risk, and realism) in these scenarios. The third study was a factor analysis (and a follow-up confirmatory factor analysis) of the elements of coercion-risk as perceived by the target group with two female samples recruited 1 year apart (Sample 1: N = 157, ages 18 29); Sample 2: N = 157, ages 18-30). Results confirmed that the scenarios could be a useful vehicle for assessing how women balance out risk and attraction to make in-the moment heterosocial drinking decisions. The factor analysis showed participants perceived two types of situations, based on whether the male character was "Familiar" or "Just Met" and perceived themselves as happier and more excited with Familiar males. However, in contrast to HIV risk studies, Familiar males were perceived as higher risk for unwanted sex. Future research will use the six scenarios that emerged from the factor analysis to study how attraction and risk perception differentially affect young adult women's social drinking decisions. PMID- 27413091 TI - A Bigger Picture: Organismal Function at the Nexus of Development, Ecology, and Evolution: An Introduction to the Symposium. AB - Over the past 40 years of research, two perspectives have dominated the study of ecomorphology at ontogenetic and evolutionary timescales. For key anatomical complexes (e.g., feeding apparatus, locomotor systems, sensory structures), morphological changes during ontogeny are often interpreted in functional terms and linked to their putative importance for fitness. Across larger timescales, morphological transformations in these complexes are examined through character stability or mutability during cladogenesis. Because the fittest organisms must pass through ontogenetic changes in size and shape, addressing transformations in morphology at different time scales, from life histories to macroevolution, has the potential to illuminate major factors contributing to phenotypic diversity. To date, most studies have relied on the assumption that organismal form is tightly constrained by the adult niche. Although this could be accurate for organisms that rapidly reach and spend a substantial portion of their life history at the adult phenotype (e.g., birds, mammals), it may not always hold true for species that experience substantial growth after one or more major fitness filters during their ontogeny (e.g., some fishes, reptiles). In such circumstances, examining the adult phenotype as the primary result of selective processes may be erroneous as it likely obscures the developmental configuration of morphology that was most critical to early survival. Given this discrepancy and its potential to mislead interpretations of how selection may shape a taxon's phenotype-this symposium addresses the question: how do we identify such ontogenetic "inertia," and how do we integrate developmental information into our phylogenetic, ecological, and functional interpretations of complex phenotypes? PMID- 27413092 TI - Dipteran Halteres: Perspectives on Function and Integration for a Unique Sensory Organ. AB - The halteres of dipteran insects (true flies) are essential mechanosensory organs for flight. These are modified hindwings with several arrays of sensory cells at their base, and they are one of the characteristic features of flies. Mechanosensory information from the halteres is sent with low latency to wing steering and head movement motoneurons, allowing direct control of body position and gaze. Analyses of the structure and dynamics of halteres indicate that they experience very small aerodynamic forces but significant inertial forces, including Coriolis forces associated with body rotations. The sensory cells at the base of the haltere detect these forces and allow the fly to correct for perturbations during flight, but new evidence suggests that this may not be their only role. This review will examine our current understanding of how these organs move, encode forces, and transmit information about these forces to the nervous system to guide behavior. PMID- 27413093 TI - Uncovering Hemocyanin Subunit Heterogeneity in Penaeid Shrimp using RNA-Seq. AB - Aquatic crustaceans can experience low levels of O2 alone but more often in combination with high levels of CO2 both in natural estuaries and in aquaculture ponds. Hemocyanin, the respiratory pigment in many crustacean species, facilitates O2 transport and is documented to change in abundance, structure, and function in response to low O2 The impacts of high CO2 on the respiratory pigment are less clear. In this synthesis we bring together data from recently published and new RNA-Seq studies toward the aims of defining the full repertoire of hemocyanin subunits, as well as their differential expression and regulation in the Penaeoidea family in response to low O2 with or without high CO2 RNA-Seq data were collected from the hepatopancreas tissues of aquacultured Pacific whiteleg shrimp Litopenaeus vannamei, wild-caught L. vannamei, and wild-caught Atlantic brown shrimp Farfantepenaeus aztecus. De novo assembly yielded high-quality stranded transcriptomes. Manual curation of the hemocyanin subunits from all three groups of penaeid shrimp confirmed the existence of a small gamma-type hemocyanin subunit (HcS), greater sequence diversity in the large gamma-type hemocyanin subunit than previously identified (HcL1-3 isoforms) and expression of a beta-type hemocyanin subunit (HcB) previously unidentified in Penaeid shrimp. Relative abundance of transcripts encoding these hemocyanin isoforms differed within and among the three species/strains. Exposure to low O2 induced expression of all of the subunits in aquacultured L. vannamei With concurrent exposure to high CO2, the number of gamma-type hemocyanin transcripts decreased while the expression of beta-type transcripts remained unchanged. Together with functional data for hemocyanins in the same shrimp species/strains, the RNA-Seq approach shows great promise to provide new insights into the connection between sequence, protein structure, and physiological function of respiratory pigments in this decapod crustacean family. PMID- 27413094 TI - Continuous and Prolonged Intravenous beta-Lactam Dosing: Implications for the Clinical Laboratory. AB - Beta-lactam antibiotics serve as a cornerstone in the management of bacterial infections because of their wide spectrum of activity and low toxicity. Since resistance rates among bacteria are continuously on the rise and the pipeline for new antibiotics does not meet this trend, an optimization of current beta-lactam treatment is needed. This review provides an overview of optimization through use of prolonged- and continuous-infusion dosing strategies compared with more traditional intermittent infusions. Included is an overview of the scientific basis for using these nontraditional prolonged- and continuous-infusion-based regimens, with a focus on major areas in which the clinical laboratory can support the clinical use of these regimens. PMID- 27413095 TI - Diagnosis of Ebola Virus Disease: Past, Present, and Future. AB - Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward. PMID- 27413097 TI - Robert Emmett Farr (1875-1932): A pioneer of pediatric regional anesthesia. AB - Surgeons influence the introduction and development of anesthesia in many ways. Robert Emmett Farr is frequently cited as the first to describe the use of brachial plexus anesthesia in children. A surgeon based in Minneapolis, Minnesota, he passionately believed that regional anesthesia was superior to general anesthesia for many surgical procedures. He wrote extensively promoting other regional techniques, including local infiltration of local anesthetics for pyloromyotomy and harelip repairs, as well as caudal blocks for lower abdominal procedures. Anesthesia texts from the early 1900's suggest that regional anesthesia was not popular as a reliable alternative to general anesthesia. Undeterred, Farr continued promoting his view that regional anesthesia was the future of surgery. We examine how Farr promoted regional anesthesia in children and adults, in a way changing surgical practice and improving clinical care. We also hope to highlight the other contributions to medicine made by this pioneer. PMID- 27413098 TI - Nicolai Kravkov's pancreotoxine. AB - The article reviews the life and work of an outstanding Russian pharmacologist Professor Nikolai Kravkov (1865-1924). Among his many scientific achievements, he worked on an extract from the pancreas of animals in the early 1920s and was successful in isolating the internal secretion, which he named "pancreotoxine." This reduced blood glucose levels in animals and diabetic humans. Kravkov's work on the isolation of pancreotoxine was going on coincidentally with F. Banting's and C. Best's research of insulin, but their methods of isolation of the hormone were quite different. PMID- 27413099 TI - Joseph Lovell, MD (1788-1836): First US army surgeon general. AB - Joseph Lovell, trained in medicine at Harvard and in military medicine/surgery by the War of 1812, became the first Surgeon General to sit on the reorganised army staff at the tender age of 29 in 1818. With a keen intellect, medical acumen, and wartime experiences for his tools and a close supporting relationship with Commanding General Jacob Jennings Brown and Secretary of War John C Calhoun (1728 1850), Lovell constructed an efficient and effective organisational and administrative framework for the new Medical Department of the US Army. Moreover, he not only redefined the role of the American military physician but also established the professional dignity, respectability and value of the medical officer among line officers and staff. Lovell's 18-year tenure came to an abrupt end, but the operational framework he created became both foundation and legacy for his successors. PMID- 27413096 TI - Modulation of Host Immunity by the Human Metapneumovirus. AB - Globally, as a leading agent of acute respiratory tract infections in children <5 years of age and the elderly, the human metapneumovirus (HMPV) has gained considerable attention. As inferred from studies comparing vaccinated and experimentally infected mice, the acquired immune response elicited by this pathogen fails to efficiently clear the virus from the airways, which leads to an exaggerated inflammatory response and lung damage. Furthermore, after disease resolution, there is a poor development of T and B cell immunological memory, which is believed to promote reinfections and viral spread in the community. In this article, we discuss the molecular mechanisms that shape the interactions of HMPV with host tissues that lead to pulmonary pathology and to the development of adaptive immunity that fails to protect against natural infections by this virus. PMID- 27413102 TI - Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes. AB - BACKGROUND: Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little is known about whether habitual dietary intake of BCAAs affects risk of T2D. METHODS: We assessed associations between cumulative consumption of BCAAs and risk of T2D among participants from three prospective cohorts: the Nurses' Health Study (NHS; followed from 1980 to 2012); NHS II (followed from 1991 to 2011); and the Health Professionals Follow-up Study (HPFS; followed from 1986 to 2010). RESULTS: We documented 16 097 incident T2D events during up to 32 years of follow-up. After adjustment for demographics and traditional risk factors, higher total BCAA intake was associated with an increased risk of T2D in men and women. In the meta analysis of all cohorts, comparing participants in the highest quintile with those in the lowest quintile of intake, hazard ratios (95%confidence intervals) were for leucine 1.13 (1.07-1.19), for isoleucine 1.13 (1.07-1.19) and for valine 1.11 (1.05-1.17) (all P for trend < 0.001). In a healthy subsample, higher dietary BCAAs were significantly associated with higher plasma levels of these amino acids (P for trend = 0.01). CONCLUSIONS: Our data suggest that high consumption of BCAAs is associated with an increased risk of T2D. PMID- 27413101 TI - At the Interface of Chemical and Biological Synthesis: An Expanded Genetic Code. AB - The ability to site-specifically incorporate noncanonical amino acids (ncAAs) with novel structures into proteins in living cells affords a powerful tool to investigate and manipulate protein structure and function. More than 200 ncAAs with diverse biological, chemical, and physical properties have been genetically encoded in response to nonsense or frameshift codons in both prokaryotic and eukaryotic organisms with high fidelity and efficiency. In this review, recent advances in the technology and its application to problems in protein biochemistry, cellular biology, and medicine are highlighted. PMID- 27413104 TI - Data Resource Profile: Children Looked After Return (CLA). PMID- 27413103 TI - Birthweight, childhood growth and left ventricular structure at age 60-64 years in a British birth cohort study. AB - BACKGROUND: High left ventricular mass (LVM) is an independent predictor of cardiovascular disease and mortality, but information relating LVM in older age to growth in early life is limited. We assessed the relationship of birthweight, height and body mass index (BMI) and overweight across childhood and adolescence with later life left ventricular (LV) structure. METHODS: We used data from the MRC National Survey of Health and Development (NSHD) on men and women born in 1946 in Britain and followed up ever since. We use regression models to relate prospective measures of birthweight and height and BMI from ages 2-20 years to LV structure at 60-64 years. RESULTS: Positive associations of birthweight with LVM and LV end diastolic volume (LVEDV) at 60-64 years were largely explained by adult height. Higher BMI, greater changes in BMI and greater accumulation of overweight across childhood and adolescence were associated with higher LVM and LVEDV and odds of concentric hypertrophy. Those who were overweight at two ages in early life had a mean LVM 11.5 g (95% confidence interval: -2.19,24.87) greater, and a mean LVEDV 10.0 ml (3.7,16.2) greater, than those who were not overweight. Associations were at least partially mediated through adult body mass index. Body size was less consistently associated with relative wall thickness (RWT), with the strongest association being observed with pubertal BMI change [0.007 (0.001,0.013) per standard deviation change in BMI 7-15 years]. The relationships between taller childhood height and LVM and LVEDV were explained by adult height. CONCLUSIONS: Given the increasing levels of overweight in contemporary cohorts of children, these findings further emphasize the need for effective interventions to prevent childhood overweight. PMID- 27413105 TI - Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy. AB - Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3 MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS induced LMP in HepG2 cells. We proposed that Spinster 1 might work as a specific molecule that linked autophagy with LMP. PFOS-induced collapse of mitochondrial transmembrane potential was cathepsin D and autophagy dependent. Addition of 3-MA relieved PFOS-induced apoptosis, which was evidenced by Hoechst assay, AV/PI staining and caspase-3 activity assay. Inhibition of autophagosome formation by Atg5 siRNA attenuated PFOS-induced apoptosis. Treatment of HepG2 cells with PFOS for 24 h impaired mitophagy, as evidenced by an increase of cells with giant mitochondria and impairment of colocalization of PINK1 with light chain 3. In summary, we report that PFOS induces autophagy-dependent apoptosis in HepG2 cells through the lysosomal-mitochondrial axis and impairment of mitophagy, suggesting that autophagy is a primary target for PFOS toxicity. These findings provide new mechanistic insights into PFOS-induced hepatotoxicity. PMID- 27413106 TI - Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells. AB - Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 uM for MXC and 126 uM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. PMID- 27413108 TI - Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice. AB - The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD diet supplemented with 0.012% PFOS compared with those fed the control diet supplemented with 0.012% PFOS. Surprisingly, serum PFOS concentrations were higher while liver PFOS concentrations were lower in mMCD-fed mice compared with corresponding control-fed mice. To determine if supplemental dietary choline could prevent PFOS-induced hepatic effects, C57BL/6 mice were fed a control diet, or a choline supplemental diet (1.2%) with or without 0.003% PFOS. Lipidomic analysis demonstrated that PFOS caused alterations in hepatic lipid metabolism in the PFOS-fed mice compared with controls, and supplemental dietary choline prevented these PFOS-induced changes. Interestingly, dietary choline supplementation also prevented PFOS-induced oxidative damage. These studies are the first to suggest that PFOS may cause hepatic steatosis and oxidative stress by effectively reducing the choline required for hepatic VLDL production and export by forming an ion pair with choline, and suggest that choline supplementation may prevent and/or treat PFOS-induced hepatic steatosis and oxidative stress. PMID- 27413107 TI - Embryonic Atrazine Exposure Elicits Alterations in Genes Associated with Neuroendocrine Function in Adult Male Zebrafish. AB - The developmental origins of health and disease (DOHaD) hypothesis states that exposure to environmental stressors early in life can elicit genome and epigenome changes resulting in an increased susceptibility of a disease state during adulthood. Atrazine, a common agricultural herbicide used throughout the Midwestern United States, frequently contaminates potable water supplies and is a suspected endocrine disrupting chemical. In our previous studies, zebrafish was exposed to 0, 0.3, 3, or 30 parts per billion (MUg/l) atrazine through embryogenesis, rinsed, and allowed to mature to adulthood. A decrease in spawning was observed with morphological alterations in offspring. In addition, adult females displayed an increase in ovarian progesterone and follicular atresia, alterations in levels of a serotonin metabolite and serotonin turnover in brain tissue, and transcriptome changes in brain and ovarian tissue supporting neuroendocrine alterations. As reproductive dysfunction is also influenced by males, this study assessed testes histology, hormone levels, and transcriptomic profiles of testes and brain tissue in the adult males. The embryonic atrazine exposure resulted in no alterations in body or testes weight, gonadosomatic index, testes histology, or levels of 11-ketotestosterone or testosterone. To further investigate potential alterations, transcriptomic profiles of adult male testes and brain tissue was completed. This analysis demonstrated alterations in genes associated with abnormal cell and neuronal growth and morphology; molecular transport, quantity, and production of steroid hormones; and neurotransmission with an emphasis on the hypothalamus-pituitary-adrenal and hypothalamus-pituitary thyroid axes. Overall, this data indicate future studies should focus on additional neuroendocrine endpoints to determine potential functional impairments. PMID- 27413100 TI - Agonists and Antagonists of TGF-beta Family Ligands. AB - The discovery of the transforming growth factor beta (TGF-beta) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-beta family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-beta family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-beta family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-beta family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-beta family signals. This article reviews our knowledge of extracellular modulation of TGF-beta growth factors by diverse proteins and their molecular mechanisms to regulate TGF-beta family signaling. PMID- 27413109 TI - From the Cover: Arsenic Induces Accumulation of alpha-Synuclein: Implications for Synucleinopathies and Neurodegeneration. AB - Synucleinopathies, including Parkinson's disease (PD), are neurodegenerative diseases characterized by accumulation of alpha-synuclein (SYN), a small neuronal protein with prion like properties that plays a central role in PD pathogenesis. SYN can misfold and generate toxic oligomers/aggregates, which can be cytotoxic. Environmental arsenic (As)-containing pesticide use correlates with increased incidence of PD. Moreover, because As exposure can lead to inhibition of autophagic flux we hypothesize that As can facilitate the accumulation of toxic SYN oligomers/aggregates and subsequent increases in markers of autophagy. We therefore examined the role of As in the oligomerization of SYN, and the consequences thereof. Chronic exposure of SH-SY5Y cells overexpressing SYN to As caused a dose-dependent oligomerization of SYN, with concomitant increases in protein ubiquitination and expression of other stress markers (protein glutathione binding, gamma-GCS, light chain 3 (LC3)-I/II, P62, and NAD(P)H dehydrogenase quinone 1), indicative of an increased proteotoxic stress. Immunocytochemical analyses revealed an accumulation of SYN, and it's colocalization with LC3, a major autophagic protein. Mice exposed to As (100 ppb) for 1 month, exhibited elevated SYN accumulation in the cortex and striatum, and elevations in protein ubiquitination and LC3-I and II levels. However, tyrosine hydroxylase (TH), an indicator of dopaminergic cell density, was upregulated in the As exposed animals. Because SYN can inhibit TH function, and As can decrease monoamine levels, As exposure possibly leads to compensatory mechanisms leading to an increase in TH expression. Our findings suggest that susceptible individuals may be at higher risk of developing synucleinopathies and/or neurodegeneration due to environmental As exposure. PMID- 27413110 TI - Editor's Highlight: Neonatal Activation of the Xenobiotic-Sensors PXR and CAR Results in Acute and Persistent Down-regulation of PPARalpha-Signaling in Mouse Liver. AB - Safety concerns have emerged regarding the potential long-lasting effects due to developmental exposure to xenobiotics. The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are critical xenobiotic-sensing nuclear receptors that are highly expressed in liver. The goal of this study was to test our hypothesis that neonatal exposure to PXR- or CAR-activators not only acutely but also persistently regulates the expression of drug-processing genes (DPGs). A single dose of the PXR-ligand PCN (75 mg/kg), CAR-ligand TCPOBOP (3 mg/kg), or vehicle (corn oil) was administered intraperitoneally to 3-day-old neonatal wild type mice. Livers were collected 24 h post-dose or from adult mice at 60 days of age, and global gene expression of these mice was determined using Affymetrix Mouse Transcriptome Assay 1.0. In neonatal liver, PCN up-regulated 464 and down regulated 449 genes, whereas TCPOBOP up-regulated 308 and down-regulated 112 genes. In adult liver, there were 15 persistently up-regulated and 22 persistently down-regulated genes following neonatal exposure to PCN, as well as 130 persistently up-regulated and 18 persistently down-regulated genes following neonatal exposure to TCPOBOP. Neonatal exposure to both PCN and TCPOBOP persistently down-regulated multiple Cyp4a members, which are prototypical-target genes of the lipid-sensor PPARalpha, and this correlated with decreased PPARalpha binding to the Cyp4a gene loci. RT-qPCR, western blotting, and enzyme activity assays in livers of wild-type, PXR-null, and CAR-null mice confirmed that the persistent down-regulation of Cyp4a was PXR and CAR dependent. In conclusion, neonatal exposure to PXR- and CAR-activators both acutely and persistently regulates critical genes involved in xenobiotic and lipid metabolism in liver. PMID- 27413111 TI - From the Cover: Tetrachlorobenzoquinone Exerts Neurological Proinflammatory Activity by Promoting HMGB1 Release, Which Induces TLR4 Clustering within the Lipid Raft. AB - Tetrachlorobenzoquinone (TCBQ) is a confirmed active metabolite of a well-known environmental pollutant pentachlorophenol (PCP). Unfortunately, there is insufficient knowledge present available on TCBQ's toxicity. Our previous studies indicated that TCBQ induces inflammatory response in vivo and in vitro; however, its exact mechanism needs further investigation. Toll-like receptors (TLRs) play a crucial role in conveying of inflammatory signaling, whilst high-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein that regulates inflammation. Indeed, this study demonstrated that TCBQ induces the secretion/translocation of HMGB1, which in turn activates its receptors, TLR family gene (especially TLR4) and receptor for advanced glycation end-products (RAGE) expressions. Consistently, the binding affinity of HMGB1 with its receptors also increased. In the case of HMGB1 or TLR4 deficiency, there were decreases in TCBQ-induced neuroinflammatory cytokine production and neuropathological changes, eg, neuronal loss, astrocyte and macrophage cells activation. Moreover, we found the mobilization of TLR4 into lipid rafts occurs in response to TCBQ exposure, lipid rafts disruptors weakened this effect, suggested lipid rafts play an essential role for TLR4-mediated signal transduction and target inflammatory cytokines expressions. In summary, our current findings revealed a previously unknown mechanism of TCBQ-induced neurological inflammation related to HMGB1-TLR4 signaling. PMID- 27413112 TI - New Quantitative Structure-Activity Relationship Models Improve Predictability of Ames Mutagenicity for Aromatic Azo Compounds. AB - Existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for aromatic azo compounds. In this study, 2 new models were built to predict Ames mutagenicity of this class of compounds. The first one made use of descriptors based on simplified molecular input-line entry system (SMILES), calculated with the CORAL software. The second model was based on the k nearest neighbors algorithm. The statistical quality of the predictions from single models was satisfactory. The performance further improved when the predictions from these models were combined. The prediction results from other QSAR models for mutagenicity were also evaluated. Most of the existing models were found to be good at finding toxic compounds but resulted in many false positive predictions. The 2 new models specific for this class of compounds avoid this problem thanks to a larger set of related compounds as training set and improved algorithms. PMID- 27413113 TI - Identification of the Additional Mitochondrial Liabilities of 2-Hydroxyflutamide When Compared With its Parent Compound, Flutamide in HepG2 Cells. AB - The androgen receptor antagonist, flutamide, is strongly associated with idiosyncratic drug-induced liver injury (DILI). Following administration, flutamide undergoes extensive first-pass metabolism to its primary metabolite, 2 hydroxyflutamide. Flutamide is a known mitochondrial toxicant; however there has been limited investigation into the potential mitochondrial toxicity of 2 hydroxyflutamide and its contribution to flutamide-induced liver injury. In this study we have used the acute glucose or galactose-conditioning of HepG2 cells to compare the mitochondrial toxicity of flutamide, 2-hydroxyflutamide and the structurally-related, non-hepatotoxic androgen receptor antagonist, bicalutamide. Compound-induced changes in mitochondrial oxygen consumption rate were assessed using Seahorse technology. Permeabilization of cells and delivery of specific substrates and inhibitors of the various respiratory complexes provided more detailed information on the origin of mitochondrial perturbations. These analyses were supported by assessment of downstream impacts including changes in cellular NAD(+)/NADH ratio. Bicalutamide was not found to be a mitochondrial toxicant, yet flutamide and 2-hydroxyflutamide significantly reduced basal and maximal respiration. Both flutamide and 2-hydroxyflutamide significantly reduced respiratory complex I-linked respiration, though 2-hydroxyflutamide also significantly decreased complex II and V-linked respiration; liabilities not demonstrated by the parent compound. This study has identified for the first time, the additional mitochondrial liabilities of the major metabolite, 2 hydroxyflutamide compared with its parent drug, flutamide. Given the rapid production of this metabolite upon administration of flutamide, but not bicalutamide, we propose that the additional mitochondrial toxicity of 2 hydroxyflutamide may fundamentally contribute to the idiosyncratic DILI seen in flutamide-treated, but not bicalutamide-treated patients. PMID- 27413114 TI - ATM Mutations in Cancer: Therapeutic Implications. AB - Activation of checkpoint arrest and homologous DNA repair are necessary for maintenance of genomic integrity during DNA replication. Germ-line mutations of the ataxia telangiectasia mutated (ATM) gene result in the well-characterized ataxia telangiectasia syndrome, which manifests with an increased cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers. Somatic ATM mutations or deletions are commonly found in lymphoid malignancies, as well as a variety of solid tumors. Such mutations may result in chemotherapy resistance and adverse prognosis, but may also be exploited by existing or emerging targeted therapies that produce synthetic lethal states. Mol Cancer Ther; 15(8); 1781-91. (c)2016 AACR. PMID- 27413117 TI - Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway. AB - Diabetes mellitus (DM) and its accompanying chronic inflammation promote tumor progression. p38 mitogen-activated protein kinase (MAPK) is an essential kinase for inflammation. The effects of p38 MAPK on epithelial-mesenchymal transition (EMT)-mediated diabetic pancreatic cancer metastasis remain unclear. Here, we demonstrate that p38 MAPK phosphorylation was significantly increased in pancreatic cancer cells treated with high glucose and in pancreatic tumors from diabetic animals. A p38 MAPK inhibitor significantly suppressed the proliferation and invasion of pancreatic cancer cells under high-glucose conditions. Moreover, p38 MAPK inhibition not only significantly decreased both the tumor volume monitored by magnetic resonance imaging and EMT-related metastasis but also increased the survival of diabetic mice bearing pancreatic tumors. Furthermore, the inflammation in diabetic animals bearing pancreatic tumors was also significantly lower after therapy. Collectively, our findings reveal that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment. PMID- 27413116 TI - The Paradox of p53: What, How, and Why? AB - Unlike the rather stereotypic image by which it was portrayed until not too many years ago, p53 is now increasingly emerging as a multifaceted transcription factor that can sometimes exert opposing effects on biological processes. This includes pro-survival activities that seem to contradict p53's canonical proapoptotic features, as well as opposing effects on cell migration, metabolism, and differentiation. Such antagonistic bifunctionality (balancing both positive and negative signals) bestows p53 with an ideal attribute to govern homeostasis. The molecular mechanisms underpinning the paradoxical activities of p53 may be related to a protein conformational spectrum (from canonical wild-type to "pseudomutant"), diversity of DNA response elements, and/or higher-order chromatin configuration. Altogether, this functional flexibility positions p53 as a transcriptional "super hub" that dictates cell homeostasis, and ultimately cell fate, by governing a hierarchy of other functional hubs. Deciphering the mechanisms by which p53 determines which hubs to engage, and how one might modulate the preferences of p53, remains a major challenge for both basic science and translational cancer medicine. PMID- 27413115 TI - The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer. AB - During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that ~20% of malignancies have alterations of the subunits of polymorphic BRG-/BRM associated factor (BAF) and Polybromo-associated BAF (PBAF) complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1 These subunits share some degree of conservation with subunits from related adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in model organisms, in which a large body of work provides insight into their roles in cancer. Here, we review the roles of BAF- and PBAF-like complexes in these organisms, and relate these findings to recent discoveries in cancer epigenomics. We review several roles of BAF and PBAF complexes in cancer, including transcriptional regulation, DNA repair, and regulation of chromatin architecture and topology. More recent results highlight the need for new techniques to study these complexes. PMID- 27413118 TI - Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2 (3-Phenylpropylamino) Benzoate. AB - Cystic fibrosis (CF) is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a phosphorylation-activated but ATP-gated chloride channel. Previous studies suggested that VX-770 [ivacaftor, N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4 dihydroquinoline-3-carboxamide], a CFTR potentiator now used in clinics, increases the open probability of CFTR by shifting the gating conformational changes to favor the open channel configuration. Recently the chloride channel blocker and CFTR potentiator 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB) has been reported to enhance CFTR activity by a mechanism that exploits the ATP hydrolysis-driven, nonequilibrium gating mechanism unique to CFTR. Surprisingly however, NPPB increased the activity of nonhydrolytic G551D-CFTR, the third most common disease-associated mutation. Here, we further investigated the mechanism of NPPB's effects on CFTR gating by assessing its interaction with well-studied VX-770. Interestingly, once G551D-CFTR was maximally potentiated by VX-770, NPPB further increased its activity. However, quantitative analysis of this drug-drug interaction suggests that this pharmacologic synergism is not due to independent actions of NPPB and VX-770 on CFTR gating; instead, our data support a dependent mechanism involving two distinct binding sites. This latter idea is further supported by the observation that the locked-open time of a hydrolysis-deficient mutant K1250A was shortened by NPPB but prolonged by VX-770. In addition, the effectiveness of NPPB, but not of VX-770, was greatly diminished in a mutant whose second nucleotide-binding domain was completely removed. Interpreting these results under the framework of current understanding of CFTR gating not only reveals insights into the mechanism of action for different CFTR potentiators but also brings us one step forward to a more complete schematic for CFTR gating. PMID- 27413120 TI - Patient portals and personal health information online: perception, access, and use by US adults. AB - Background: Access to online patient portals is key to improving care, but we have limited understanding of patient perceptions of online portals and the characteristics of people who use them. Methods: Using a national survey of 3677 respondents, we describe perceptions and utilization of online personal health information (PHI) portals. Results: Most respondents (92%) considered online PHI access important, yet only 34% were offered access to online PHI by a health care provider, and just 28% accessed online PHI in the past year. While there were no differences across race or ethnicity in importance of access, black and Hispanic respondents were significantly less likely to be offered access ( P = .006 and <.001, respectively) and less likely to access their online PHI ( P = .041 and <.001, respectively) compared to white and non-Hispanic respondents. Conclusion: Health care providers are crucial to the adoption and use of online patient portals and should be encouraged to offer consistent access regardless of patient race and ethnicity. PMID- 27413119 TI - Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity. AB - Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4 by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-alpha carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. PMID- 27413121 TI - Improving the discoverability, accessibility, and citability of omics datasets: a case report. AB - Although omics datasets represent valuable assets for hypothesis generation, model testing, and data validation, the infrastructure supporting their reuse lacks organization and consistency. Using nuclear receptor signaling transcriptomic datasets as proof of principle, we developed a model to improve the discoverability, accessibility, and citability of published omics datasets. Primary datasets were retrieved from archives, processed to extract data points, then subjected to metadata enrichment and gap filling. The resulting secondary datasets were exposed on responsive web pages to support mining of gene lists, discovery of related datasets, and single-click citation integration with popular reference managers. Automated processes were established to embed digital object identifier-driven links to the secondary datasets in associated journal articles, small molecule and gene-centric databases, and a dataset search engine. Our model creates multiple points of access to reprocessed and reannotated derivative datasets across the digital biomedical research ecosystem, promoting their visibility and usability across disparate research communities. PMID- 27413122 TI - Congestive heart failure information extraction framework for automated treatment performance measures assessment. AB - Objective: This paper describes a new congestive heart failure (CHF) treatment performance measure information extraction system - CHIEF - developed as part of the Automated Data Acquisition for Heart Failure project, a Veterans Health Administration project aiming at improving the detection of patients not receiving recommended care for CHF. Design: CHIEF is based on the Apache Unstructured Information Management Architecture framework, and uses a combination of rules, dictionaries, and machine learning methods to extract left ventricular function mentions and values, CHF medications, and documented reasons for a patient not receiving these medications. Measurements: The training and evaluation of CHIEF were based on subsets of a reference standard of various clinical notes from 1083 Veterans Health Administration patients. Domain experts manually annotated these notes to create our reference standard. Metrics used included recall, precision, and the F 1 -measure. Results: In general, CHIEF extracted CHF medications with high recall (>0.990) and good precision (0.960 0.978). Mentions of Left Ventricular Ejection Fraction were also extracted with high recall (0.978-0.986) and precision (0.986-0.994), and quantitative values of Left Ventricular Ejection Fraction were found with 0.910-0.945 recall and with high precision (0.939-0.976). Reasons for not prescribing CHF medications were more difficult to extract, only reaching fair accuracy with about 0.310-0.400 recall and 0.250-0.320 precision. Conclusion: This study demonstrated that applying natural language processing to unlock the rich and detailed clinical information found in clinical narrative text notes makes fast and scalable quality improvement approaches possible, eventually improving management and outpatient treatment of patients suffering from CHF. PMID- 27413123 TI - Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial. AB - BACKGROUND: The bioavailability of potassium should be considered in setting requirements, but to our knowledge, the bioavailability from individual foods has not been determined. Potatoes provide 19-20% of potassium in the American diet. OBJECTIVE: We compared the bioavailability and dose response of potassium from nonfried white potatoes with skin [targeted at 20, 40, and 60 milliequivalents (mEq) K] and French fries (40 mEq K) with potassium gluconate at the same doses when added to a basal diet that contained ~60 mEq K. DESIGN: Thirty-five healthy, normotensive men and women with a mean +/- SD age of 29.7 +/- 11.2 y and body mass index (in kg/m(2)) of 24.3 +/- 4.4 were enrolled in a single-blind, crossover, randomized controlled trial. Participants were partially randomly assigned to the order of testing for nine 5-d interventions of additional potassium as follows: 0 (control; repeated at phases 1 and 5), 20, 40, and 60 mEq K/d consumed as a potassium gluconate supplement or as unfried potato or 40 mEq K from French fries completed at phase 9. The bioavailability of potassium was determined from the area under the curve (AUC) of serial blood draws and cumulative urinary excretion during a 24-h period and from a kinetic analysis. The effects of the potassium source and dose on the change in blood pressure and augmentation index (AIx) were determined. RESULTS: The serum potassium AUC increased with the dose (P < 0.0001) and did not differ because of the source (P = 0.53). Cumulative 24-h urinary potassium also increased with the dose (P < 0.0001) and was greater with the potato than with the supplement (P < 0.0001). The kinetic analysis showed the absorption efficiency was high across all interventions (>94% +/- 12%). There were no significant differences in the change in blood pressure or AIx with the treatment source or dose. CONCLUSIONS: The bioavailability of potassium is as high from potatoes as from potassium gluconate supplements. Future studies that measure the effect of dietary potassium on blood pressure will need to evaluate the effect of various dietary sources on potassium retention and in both normal and hypertensive populations. This trial was registered at clinicaltrials.gov as NCT01881295. PMID- 27413124 TI - Probable insomnia is associated with future total energy intake and diet quality in men. AB - BACKGROUND: Insomnia is associated with several adverse health outcomes. Small clinical studies have suggested that an inferior nutrition status is a potential explanation, but to our knowledge, this possibility has not been examined in a large-scale, population-based cohort study. OBJECTIVE: We examined whether individuals with probable insomnia and individual insomnia symptoms had greater energy intake and a lower diet quality as assessed with the use of the Alternate Healthy Eating Index (AHEI) 2 y later. DESIGN: A cohort study of 15,273 US men aged 58-93 y who were free of cancer, cardiovascular diseases, and diabetes and were participating in the Health Professionals Follow-Up Study reported information on insomnia symptoms in 2004. Dietary intake was assessed with the use of a food-frequency questionnaire in 2002 and 2006. We calculated the adjusted mean differences of total energy intake in 2006 and the AHEI-component scores and their 95% CIs between subjects with and without probable insomnia in 2004 and also across categories for each insomnia symptom while adjusting for related covariates. RESULTS: After dietary intake in 2002, major chronic conditions, and other potential confounders were controlled for, men with probable insomnia had a mean higher consumption of 35.8 kcal/d (95% CI: 17.4, 54.1 kcal/d) and had lower scores in 3 individual AHEI components (trans fat, vegetables, and sodium), which denoted higher consumption of trans fat and sodium and lower intake of vegetables (P <= 0.01 for all). For individual insomnia symptoms, nonrestorative sleep and a difficulty maintaining sleep were associated with higher energy intake (P-trend <= 0.007 for both). A similar trend was observed in men who had difficulty initiating sleep (P-trend = 0.07). We also observed a significant association between the difficulty of initiating sleep and a lower AHEI score 2 y later (P-trend = 0.004). CONCLUSION: Probable insomnia is associated with higher intakes of total energy, trans fat, and sodium and lower intake of vegetables. PMID- 27413126 TI - Comparison of associations of maternal peri-pregnancy and paternal anthropometrics with child anthropometrics from birth through age 7 y assessed in the Danish National Birth Cohort. AB - BACKGROUND: Maternal prepregnancy adiposity may influence child adiposity beyond the transmitted genetic effects, which, if true, may accelerate the obesity epidemic, but the evidence for this mechanism is inconsistent. OBJECTIVE: The aim was to assess whether the associations of maternal body mass index (BMI) with child anthropometric measurements from birth through infancy and at 7 y of age exceed those of paternal associations. DESIGN: In the Danish National Birth Cohort, information on parental and child anthropometric measures is available for 30,655 trio families from maternal interviews during pregnancy and the postpartum period and from a 7-y follow-up. By using multiple linear and logistic regression models of child SD (z) scores of weight and BMI at birth, 5 mo, 12 mo, and 7 y of age, and of child overweight at age 7 y, we compared associations with maternal prepregnancy and postpartum BMI z scores and with paternal BMI z scores. RESULTS: When comparing maternal-child and paternal-child BMI z score associations, the strongest associations were observed with mothers' BMI at birth [maternal and paternal BMI z scores: 0.143 (95% CI: 0.130, 0.155) and 0.017 (95% CI: 0.005, 0.029), respectively] and throughout infancy, but the relative difference in the associations declined by child age [for BMI z score at child age 7 y per maternal and paternal BMI z scores: 0.208 (95% CI: 0.196, 0.220) and 0.154 (95% CI: 0.143, 0.166), respectively]. At 7 y of age, ORs of child overweight were 2.30 (95% CI: 1.99, 2.67) by maternal overweight and 1.96 (95% CI: 1.74, 2.21) by paternal overweight. There were no differences between the results based on maternal BMI before and after pregnancy or on child's weight adjusted for length or height. CONCLUSIONS: The associations of child weight and BMI with maternal BMI were stronger than with paternal BMI. The differences between the associations were strong at birth but declined with child aging. PMID- 27413125 TI - Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial. AB - BACKGROUND: To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. OBJECTIVE: We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free living subjects with phenylketonuria. DESIGN: This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15-49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. RESULTS: The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean +/- SE increase in plasma Phe (62 +/- 40 MUmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 +/- 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (-85 +/- 40 MUmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 +/- 34 MUmol/L, GMP-MFs = 497 +/- 34 MUmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. CONCLUSIONS: GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP MFs than with AA-MFs may enhance dietary adherence for individuals with phenylketonuria. This trial was registered at www.clinicaltrials.gov as NCT01428258. PMID- 27413127 TI - Effectiveness of a weight loss intervention in postpartum women: results from a randomized controlled trial in primary health care. AB - BACKGROUND: Reproduction has been identified as an important factor for long-term weight gain among women. A previous efficacy trial has successfully produced postpartum weight loss; however, the effectiveness of this intervention needs to be established. OBJECTIVE: This study was designed to evaluate the short- and long-term effectiveness of a diet behavior modification treatment to produce weight loss in postpartum women within the primary health care setting in Sweden. DESIGN: During 2011-2014, 110 women with a self-reported body mass index (BMI; in kg/m(2)) of >=27 at 6-15 wk postpartum were randomly assigned to the diet behavior modification group (D group) or the control group (C group). Women randomly assigned to the D group (n = 54) received a structured 12-wk diet behavior modification treatment by a dietitian and were instructed to gradually implement a diet plan based on the Nordic Nutrition Recommendations and to self weigh >=3 times/wk. Women randomly assigned to the C group (n = 56) were given a brochure on healthy eating. The primary outcome was change in body weight after 12 wk and 1 y. The retention rate was 91% and 85% at 12 wk and 1 y, respectively. RESULTS: At baseline, women had a median (1st, 3rd quartile) BMI of 31.0 (28.8, 33.6), and 84% were breastfeeding. After 12 wk, median weight change in the D group was -6.1 kg (-8.4, -3.2 kg) compared with -1.6 kg (-3.5, -0.4 kg) in the C group (P < 0.001). The difference was maintained at the 1-y follow-up for the D group, -10.0 kg (-11.7, -5.9 kg) compared with -4.3 kg (-10.2, -1.0 kg) in the C group (P = 0.004). In addition, the D group reduced BMI, waist circumference, hip circumference, and body fat percentage more than did the C group at both 12 wk and 1 y (all P < 0.05). CONCLUSION: A low-intensity diet treatment delivered by a dietitian within the primary health care setting can produce clinically relevant and sustainable weight loss in postpartum women with overweight and obesity. This trial was registered at clinicaltrials.gov as NCT01949558. PMID- 27413128 TI - Best (but oft-forgotten) practices: propensity score methods in clinical nutrition research. AB - In observational studies, treatment assignment is a nonrandom process and treatment groups may not be comparable in their baseline characteristics, a phenomenon known as confounding. Propensity score (PS) methods can be used to achieve comparability of treated and nontreated groups in terms of their observed covariates and, as such, control for confounding in estimating treatment effects. In this article, we provide a step-by-step guidance on how to use PS methods. For illustrative purposes, we used simulated data based on an observational study of the relation between oral nutritional supplementation and hospital length of stay. We focused on the key aspects of PS analysis, including covariate selection, PS estimation, covariate balance assessment, treatment effect estimation, and reporting. PS matching, stratification, covariate adjustment, and weighting are discussed. R codes and example data are provided to show the different steps in a PS analysis. PMID- 27413129 TI - ShopSmart 4 Health: results of a randomized controlled trial of a behavioral intervention promoting fruit and vegetable consumption among socioeconomically disadvantaged women. AB - BACKGROUND: Behavioral interventions show potential for promoting increased fruit and vegetable consumption in the general population. However, little is known about their effectiveness or cost-effectiveness among socioeconomically disadvantaged groups, who are less likely to consume adequate fruit and vegetables. OBJECTIVE: This study investigated the effects and costs of a behavior change intervention for increasing fruit and vegetable purchasing and consumption among socioeconomically disadvantaged women. DESIGN: ShopSmart 4 Health was a randomized controlled trial involving a 3-mo retrospective baseline data collection phase [time (T) 0], a 6-mo intervention (T1-T2), and a 6-mo no intervention follow-up (T3). Socioeconomically disadvantaged women who were primary household shoppers in Melbourne, Australia, were randomly assigned to either a behavior change intervention arm (n = 124) or a control arm (n = 124). Supermarket transaction (sales) data and surveys measured the main outcomes: fruit and vegetable purchases and self-reported fruit and vegetable consumption. RESULTS: An analysis of supermarket transaction data showed no significant intervention effects on vegetable or fruit purchasing at T2 or T3. Participants in the behavior change intervention arm reported consumption of significantly more vegetables during the intervention (T2) than did controls, with smaller intervention effects sustained at 6 mo postintervention (T3). Relative to controls, vegetable consumption increased by ~0.5 serving . participant(-1) . d( 1) from baseline to T2 and remained 0.28 servings/d higher than baseline at T3 among those who received the intervention. There was no intervention effect on reported fruit consumption. The behavior change intervention cost A$3.10 (in Australian dollars) . increased serving of vegetables(-1) . d(-1)CONCLUSIONS: This behavioral intervention increased vegetable consumption among socioeconomically disadvantaged women. However, the lack of observed effects on fruit consumption and on both fruit and vegetable purchasing at intervention stores suggests that further investigation of effective nutrition promotion approaches for this key target group is required. The ShopSmart 4 Health trial was registered at www.isrctn.com as ISRCTN48771770. PMID- 27413130 TI - Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial. AB - BACKGROUND: It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR). OBJECTIVE: We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects. DESIGN: This double blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged >=65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index. RESULTS: In total, 222 subjects (55% women) with a mean +/- SD age and body mass index (BMI; in kg/m(2)) of 71 +/- 4 y and 30 +/- 4, respectively, completed the study. Subjects' baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean +/- SD serum 25(OH)D increased from 20 +/- 7 to 26 +/- 7 ng/mL in the low-dose arm (P < 0.0001) and from 21 +/- 8 to 36 +/- 10 ng/mL in the high-dose arm (P < 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high- [2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D. CONCLUSION: Vitamin D3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals. This trial was registered at clinicaltrials.gov as NCT01315366. PMID- 27413132 TI - How much do we know about the heritability of BMI? PMID- 27413131 TI - Dietary flavonoid intake and risk of incident depression in midlife and older women. AB - BACKGROUND: The impact of dietary flavonoid intakes on risk of depression is unclear. OBJECTIVE: We prospectively examined associations between estimated habitual intakes of dietary flavonoids and depression risk. DESIGN: We followed 82,643 women without a previous history of depression at baseline from the Nurses' Health Study [(NHS) aged 53-80 y] and the Nurses' Health Study II [(NHSII) aged 36-55 y]. Intakes of total flavonoids and subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, and proanthocyanidins) were calculated from validated food-frequency questionnaires collected every 2-4 y. Depression was defined as physician- or clinician diagnosed depression or antidepressant use and was self-reported in response to periodic questionnaires. Cox proportional hazards models were performed to examine associations. RESULTS: A total of 10,752 incident depression cases occurred during a 10-y follow-up. Inverse associations between flavonol, flavone, and flavanone intakes and depression risk were observed. Pooled multivariable adjusted HRs (95% CIs) were 0.93 (0.88, 0.99), 0.92 (0.86, 0.98), and 0.90 (0.85, 0.96) when comparing the highest (quintile 5) with the lowest (quintile 1) quintiles, respectively, with evidence of linear trends across quintiles (P-trend = 0.0004-0.08). In flavonoid-rich food-based analyses, the HR was 0.82 (95% CI: 0.74, 0.91) among participants who consumed >=2 servings citrus fruit or juices/d compared with <1 serving/wk. In the NHS only, total flavonoids, polymers, and proanthocyanidin intakes showed significantly (9-12%) lower depression risks. In analyses among late-life NHS participants (aged >=65 y at baseline or during follow-up), for whom we were able to incorporate depressive symptoms into the outcome definition, higher intakes of all flavonoid subclasses except for flavan 3-ols were associated with significantly lower depression risk; flavones and proanthocyanidins showed the strongest associations (HR for both: 0.83; 95% CI: 0.77, 0.90). CONCLUSIONS: Higher flavonoid intakes may be associated with lower depression risk, particularly among older women. Further studies are needed to confirm these associations. PMID- 27413133 TI - Lifestyle intervention in psoriasis: a new avenue for treatment? PMID- 27413134 TI - Potatoes and risk of obesity, type 2 diabetes, and cardiovascular disease in apparently healthy adults: a systematic review of clinical intervention and observational studies. AB - BACKGROUND: Potatoes have been related to increased risks of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD) mainly because of their high glycemic index. OBJECTIVE: We conducted a systematic review to evaluate the relation between intake of potatoes and risks of obesity, T2D, and CVD in apparently healthy adults. DESIGN: MEDLINE, Embase, the Web of Science, and the Cochrane Central Register of Controlled Trials were searched for intervention and prospective observational studies that investigated adults without any known illnesses at baseline, recorded intake of potatoes, and measured adiposity (body weight, body mass index, or waist circumference), cases of T2D, cases of cardiovascular events, or risk markers thereof. RESULTS: In total, 13 studies were deemed eligible; 5 studies were related to obesity, 7 studies were related to T2D, and one study was related to CVD. Only observational studies were identified; there were 3 studies with moderate, 9 studies with serious, and one study with critical risk of bias. The association between potatoes (not including french fries) and adiposity was neutral in 2 studies and was positive in 2 studies. French fries were positively associated with adiposity in 3 of 3 studies. For T2D, 2 studies showed a positive association, whereas 5 studies showed no or a negative association with intake of potatoes and T2D. French fries were positively associated with T2D in 3 of 3 studies that distinguished this relation. For CVD, no association was observed. CONCLUSIONS: The identified studies do not provide convincing evidence to suggest an association between intake of potatoes and risks of obesity, T2D, or CVD. French fries may be associated with increased risks of obesity and T2D although confounding may be present. In this systematic review, only observational studies were identified. These findings underline the need for long-term randomized controlled trials. This trial was registered at the PROSPERO International prospective register of systematic reviews (www.crd.york.ac.uk/PROSPERO/) as CRD42015026491. PMID- 27413135 TI - More results but no clear conclusion on selenium and cancer. PMID- 27413136 TI - Feasibility of collecting 24-h urine to monitor sodium intake in the National Health and Nutrition Examination Survey. AB - BACKGROUND: Twenty-four-hour urine sodium excretion is recommended for monitoring population sodium intake. Because of concerns about participation and completion, sodium excretion has not been collected previously in US nationally representative surveys. OBJECTIVE: We assessed the feasibility of implementing 24 h urine collections as part of a nationally representative survey. DESIGN: We selected a random half sample of nonpregnant US adults aged 20-69 y in 3 geographic locations of the 2013 NHANES. Participants received explicit instructions, started and ended the urine collection in a urine study mobile examination center, and answered questions about their collection. Among those with a complete 24-h urine collection, a random one-half were asked to collect a second 24-h urine sample. Sodium, potassium, chloride, and creatinine excretion were analyzed. RESULTS: The final NHANES examination response rate for adults aged 20-69 y in these 3 study locations was 71%. Of those examined (n = 476), 282 (59%) were randomly selected to participate in the 24-h urine collection. Of these, 212 persons [75% of those selected for 24-h urine collection; 53% (equal to 71% * 75% of those selected for the NHANES)] collected a complete initial 24-h specimen and 92 persons (85% of 108 selected) collected a second complete 24-h urine sample. More men than women completed an initial collection (P = 0.04); otherwise, completion did not vary by sociodemographic characteristics, body mass index, education, or employment status for either collection. Mean 24-h urine volume and sodium excretion were 1964 +/- 1228 mL and 3657 +/- 2003 mg, respectively, for the first 24-h urine sample, and 2048 +/- 1288 mL and 3773 +/- 1891 mg, respectively, for the second collection. CONCLUSION: Given the 53% final component response rate and 75% completion rate, 24-h urine collections were deemed feasible and implemented in the NHANES 2014 on a subsample of adults aged 20-69 y to assess population sodium intake. This study was registered at clinicaltrials.gov as NCT02723682. PMID- 27413139 TI - Immunophenotypes of Chronic Myelomonocytic Leukemia (CMML) Subtypes by Flow Cytometry: A Comparison of CMML-1 vs CMML-2, Myeloproliferative vs Dysplastic, De Novo vs Therapy-Related, and CMML-Specific Cytogenetic Risk Subtypes. AB - OBJECTIVES: We sought to immunophenotype blasts, monocytes, and granulocytes in chronic myelomonocytic leukemias (CMMLs) and compare CMML subtypes, to identify if significant antigen expression differences existed. METHODS: Bone marrow blasts, monocytes, and granulocytes from CMML subgroups (n = 30; World Health Organization types 1/2, proliferative/dysplastic, therapy related/de novo, and low/intermediate/high cytogenetic risk) were immunophenotypically compared by flow cytometry with 10 nonneoplastic control marrows. RESULTS: Aberrancies were present in blasts of 26 (87%) of 30 CMMLs (26 diagnostic; four follow-up) and six (60%) of 10 controls (P = .089), monocytes of 28 (93%) of 30 CMMLs and six (60%) of 10 controls (P = .026), and granulocytes of eight (28%) of 29 CMMLs and zero of 10 controls (P = .166). Underexpression of CD14 and CD15 on monocytes was more common in CMMLs compared with controls (P = .008 and P = .043). Statistical analysis showed no significant difference in antigen expression between the CMML subgroups on blasts or monocytes; granulocytes demonstrated more common HLA-DR expression in CMML-2 vs CMML-1. CONCLUSIONS: These findings confirm heterogeneity within CMML subgroups and find no specific qualitative or quantitative findings characteristic of a subgroup. PMID- 27413140 TI - Neural changes induced by antipsychotic administration in adolescence: A review of studies in laboratory rodents. AB - Adolescence is characterized by major remodelling processes in the brain. Use of antipsychotic drugs (APDs) in adolescents has increased dramatically in the last 20 years; however, our understanding of the neurobiological consequences of APD treatment on the adolescent brain has not kept the same pace and significant concerns have been raised. In this review, we examined currently available preclinical studies of the effects of APDs on the adolescent brain. In animal models of neuropsychiatric disorders, adolescent APD treatment appears to be protective against selected structural, behavioural and neurochemical phenotypes. In "neurodevelopmentally normal" adolescent animals, a range of short- and long term alterations in behaviour and neurochemistry have been reported. In particular, the adolescent brain appears to be sensitive to long-term locomotor/reward effects of chronic atypical APDs in contrast with the outcomes in adults. Long-lasting changes in dopaminergic, glutamatergic and gamma-amino butyric acid-ergic systems induced by adolescent APD administration have been observed in the nucleus accumbens. A detailed examination of other potential target regions such as striatum, prefrontal cortex and ventral tegmental area is still required. Through identification of specific neural pathways targeted by adolescent APD treatment, future studies will expand the current knowledge on long-term neural outcomes which are of translational value. PMID- 27413138 TI - Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review. AB - To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum, B. breve , and B. infantis ) and Lactobacillus (eg, L. helveticus , and L. rhamnosus ), with doses between 108 and 1010 colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future. PMID- 27413141 TI - ASHP national survey of pharmacy practice in hospital settings: Monitoring and patient education-2015. AB - PURPOSE: The results of the 2015 ASHP national survey of pharmacy practice in hospital settings are presented. METHODS: A stratified random sample of pharmacy directors at 1432 U.S. general and children's medical-surgical hospitals were surveyed using a mixed-mode method. IMS Health supplied data on hospital characteristics; the survey sample was drawn from IMS's hospital database. RESULTS: The survey response rate was 22.7%. Since the 2000 survey, the proportion of hospitals reporting that pharmacists monitor at least 75% of patients has increased from 20.3% to 57.8%. The use of therapeutic drug monitoring has increased from 63.0% to 70.6% since the 2012 survey. The percentage of hospitals reporting that pharmacists have primary responsibility for discharge counseling has increased from 1.2% to 7.3% since the 2012 survey, with 33.8% of hospitals reporting pharmacist counseling of at-risk patients. Virtually all hospitals (97.5%) have partially or completely implemented electronic health records; most have computerized prescriber-order-entry (84.1%) and barcode-assisted medication administration (93.7%) systems. At an increasing percentage of hospitals (86.2% in the 2015 survey), medication orders are reviewed by a pharmacist before a dose is made available and administered to a patient. CONCLUSION: The role of pharmacists in measuring, monitoring, and managing medication use in health systems continues to be significant, important, and growing. The evolution of electronic health information and technologies that make this information more readily available to patients is transforming healthcare in a positive way and enabling pharmacists to more efficiently contribute to improving medication use. PMID- 27413137 TI - Genetic and environmental effects on body mass index from infancy to the onset of adulthood: an individual-based pooled analysis of 45 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) study. AB - BACKGROUND: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. OBJECTIVES: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. DESIGN: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. RESULTS: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. CONCLUSIONS: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity. PMID- 27413142 TI - Elevating pharmacists' scope of practice through a health-system clinical privileging process. AB - PURPOSE: The privileging of pharmacists for clinical activities and the impact that privileging has on enhancing the scope of pharmacy practice in health systems are reviewed. SUMMARY: Health-system pharmacists or pharmacy leaders must gain a thorough understanding of the credentialing and privileging process as they broaden their scope of practice. Clinical privileging affords an expanded scope of practice that is recognized at the institutional level and formally elevates the pharmacist to that of a nonphysician provider. The installation of privileging processes is expected to take many months to complete for individual institutions and should begin now in anticipation of provider status. Model institutions, including Truman Medical Centers, Johns Hopkins Hospital, and The Ohio State University Wexner Medical Center, are highlighted in this article and provide their individual approach to clinical privileging that can be applied to other institutions. The development and evaluation of these programs have given valuable insight into how this individual approach translates to health systems across the country and how the pharmacy profession can continue to unite to convey the value of pharmacists in improving patient care. CONCLUSION: In preparation for the potential approval of pharmacist provider status across the United States, it is essential that pharmacists are privileged by the medical staff at their respective institution. Clinical privileges must be strategically developed with a focus on cost and quality aims and meeting the needs of patients. Implementation and maintenance of high-performing pharmacy privileging programs require both successful leadership and management skills and an understanding of the interprofessional nature of healthcare. PMID- 27413143 TI - Corrigendum. AB - Hori T, Ogura Y, Yagi S, et al. How Do Transplant Surgeons Accomplish Optimal Portal Venous Flow During Living-Donor Liver Transplantation? Noninvasive Measurement of Indocyanine Green Elimination Rate. Surg Innov 2014;21:43-51.In the above version of the article, the affiliation of the author, Walid M. El Moghazy, was incorrectly listed as Kyoto University Hospital, Kyoto, Japan. His correct affiliation should be, Department of Surgery, Sohag University, Egypt. PMID- 27413144 TI - The Influence of Systemic Immune Response and Sleep Modulation on the Secondary Effects of Traumatic Brain Injury in the Rodent Model. PMID- 27413145 TI - Periodicity versus Prediction in Sensory Perception. PMID- 27413146 TI - Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports. AB - Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective beta-band (8-16 and 18-30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and beta band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive beta-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective beta-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision making. SIGNIFICANCE STATEMENT: Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research on the human brain has isolated abstract neural signatures of decision formation that are independent of specific sensory and motor requirements. Here, we examine the functional distinctions between the two distinct classes of decision variable signal during decisions with deferred actions with and without foreknowledge of stimulus-effector mapping. We find salient distinctions in the dynamics of abstract versus effector-selective decision signals in the human brain, in terms of sustainment through response delays and contingency on foreknowledge of stimulus-response mapping. PMID- 27413147 TI - IL4-10 Fusion Protein Is a Novel Drug to Treat Persistent Inflammatory Pain. AB - Chronic pain is a major clinical problem that is difficult to treat and requires novel therapies. Although most pain therapies primarily target neurons, neuroinflammatory processes characterized by spinal cord and dorsal root ganglion production of proinflammatory cytokines play an important role in persistent pain states and represent potential therapeutic targets. Anti-inflammatory cytokines are attractive candidates to regulate aberrant neuroinflammatory processes, but the therapeutic potential of these cytokines as stand-alone drugs is limited. Their optimal function requires concerted actions with other regulatory cytokines, and their relatively small size causes rapid clearance. To overcome these limitations, we developed a fusion protein of the anti-inflammatory cytokines interleukin 4 (IL4) and IL10. The IL4-10 fusion protein is a 70 kDa glycosylated dimeric protein that retains the functional activity of both cytokine moieties. Intrathecal administration of IL4-10 dose-dependently inhibited persistent inflammatory pain in mice: three IL4-10 injections induced full resolution of inflammatory pain in two different mouse models of persistent inflammatory pain. Both cytokine moieties were required for optimal effects. The IL4-10 fusion protein was more effective than the individual cytokines or IL4 plus IL10 combination therapy and also inhibited allodynia in a mouse model of neuropathic pain. Mechanistically, IL4-10 inhibited the activity of glial cells and reduced spinal cord and dorsal root ganglion cytokine levels without affecting paw inflammation. In conclusion, we developed a novel fusion protein with improved efficacy to treat pain, compared with wild-type anti-inflammatory cytokines. The IL4-10 fusion protein has potential as a treatment for persistent inflammatory pain. SIGNIFICANCE STATEMENT: The treatment of chronic pain is a major clinical and societal challenge. Current therapies to treat persistent pain states are limited and often cause major side effects. Therefore, novel analgesic treatments are urgently needed. In search of a novel drug to treat chronic pain, we developed a fusion protein consisting of two prototypic regulatory cytokines, interleukin 4 (IL4) and IL10. The work presented in this manuscript shows that this IL4-10 fusion protein overcomes some major therapeutic limitations of pain treatment with individual cytokines. The IL4-10 fusion protein induces full resolution of persistent inflammatory pain in two different mouse models. These novel findings are significant, as they highlight the IL4-10 fusion protein as a long-needed potential new drug to stop persistent pain states. PMID- 27413148 TI - In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain. AB - We provide a comparative in vivo examination of the brain network-based distribution of two hallmarks of Alzheimer's disease (AD) pathology in cognitively normal individuals: (1) Tau, detected with a novel positron emission tomography (PET) tracer known as (18)F-AV-1451; and (2) amyloid-beta, quantified with (11)C-PiB PET. We used a high-resolution graph-based approach to investigate local-to-local and local-to-distributed cortical associations between the maps of Tau, amyloid-beta, and gray matter intensity. Our study shows that Tau and amyloid-beta deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, Tau and amyloid-beta accumulations have strong network interdigitations in heteromodal and associative areas of the cortical mantle, particularly the inferior-lateral temporal lobe. These findings contribute significantly to our understanding of how these two main hallmarks of AD pathology propagate across the elderly human brain. SIGNIFICANCE STATEMENT: It has been postulated that Alzheimer's disease (AD) pathology interacts and resides within system-level circuits of the human brain, long before the onset of cognitive symptoms. However, a side-by-side comparison of tissue loss, amyloid beta, and Tau deposition in early stages of the disease has been precluded until the recent advent of Tau tracer-based neuroimaging. In this study, we used Tau positron emission tomography and network analyses to disentangle these pathological relationships. We found that Tau and amyloid-beta deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, we uncovered the network interdigitations of Tau and amyloid-beta in the cortical mantle. These findings contribute significantly to our understanding of how two main hallmarks of AD pathology propagate across the elderly human brain. PMID- 27413150 TI - Serotonin and Antidepressant SSRIs Inhibit Rat Neuroendocrine Dopamine Neurons: Parallel Actions in the Lactotrophic Axis. AB - Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression, but sexual side effects often compromise compliance. These reproductive dysfunctions are likely mediated by elevations of the hormone prolactin. Yet, how serotonin (5-HT) and SSRIs cause changes in prolactin secretion is not known. Here, using in vitro whole-cell patch-clamp recordings, we show that 5-HT hyperpolarizes and abolishes phasic discharge in rat neuroendocrine tuberoinfundibular dopamine (TIDA) neurons, the main inhibitor of prolactin secretion. This process is underpinned by 5-HT1A receptor-mediated activation of G-protein-coupled inwardly rectifying K(+)-like currents. We further demonstrate that the SSRIs, fluoxetine and sertraline, directly suppress TIDA neuron activity through parallel effects, independent of 5-HT transmission. This inhibition involves decreased intrinsic excitability and a slowing of TIDA network rhythms. These findings indicate that SSRIs may inhibit neuroendocrine dopamine release through both 5-HT-dependent and -independent actions, providing a mechanistic explanation for, and potential molecular targets for the amelioration of, the hyperprolactinemia and sexual dysfunction associated with these drugs. SIGNIFICANCE STATEMENT: Depression affects approximately one-tenth of the population and is commonly treated with selective serotonin reuptake inhibitors (SSRIs; e.g., Prozac). Yet, many patients withdraw from SSRI therapy due to sexual side effects (e.g., infertility, menstrual disturbances, and impotence). Although it is generally accepted that sexual side effects are due to the ability of these drugs to elevate blood levels of the hormone prolactin, the mechanism for this hormonal imbalance is not known. Here, we show that SSRIs can inhibit hypothalamic dopamine neurons that normally suppress the secretion of prolactin. Intriguingly this inhibition can be explained both by increased serotonin activity and also by parallel serotonin-independent actions. PMID- 27413149 TI - Compartmentalized Regulation of Parkin-Mediated Mitochondrial Quality Control in the Drosophila Nervous System In Vivo. AB - In neurons, the normal distribution and selective removal of mitochondria are considered essential for maintaining the functions of the large asymmetric cell and its diverse compartments. Parkin, a E3 ubiquitin ligase associated with familial Parkinson's disease, has been implicated in mitochondrial dynamics and removal in cells including neurons. However, it is not clear how Parkin functions in mitochondrial turnover in vivo, or whether Parkin-dependent events of the mitochondrial life cycle occur in all neuronal compartments. Here, using the live Drosophila nervous system, we investigated the involvement of Parkin in mitochondrial dynamics, distribution, morphology, and removal. Contrary to our expectations, we found that Parkin-deficient animals do not accumulate senescent mitochondria in their motor axons or neuromuscular junctions; instead, they contain far fewer axonal mitochondria, and these displayed normal motility behavior, morphology, and metabolic state. However, the loss of Parkin did produce abnormal tubular and reticular mitochondria restricted to the motor cell bodies. In addition, in contrast to drug-treated, immortalized cells in vitro, mature motor neurons rarely displayed Parkin-dependent mitophagy. These data indicate that the cell body is the focus of Parkin-dependent mitochondrial quality control in neurons, and argue that a selection process allows only healthy mitochondria to pass from cell bodies to axons, perhaps to limit the impact of mitochondrial dysfunction. SIGNIFICANCE STATEMENT: Parkin has been proposed to police mitochondrial fidelity by binding to dysfunctional mitochondria via PTEN (phosphatase and tensin homolog)-induced putative kinase 1 (PINK1) and targeting them for autophagic degradation. However, it is unknown whether and how the PINK1/Parkin pathway regulates the mitochondrial life cycle in neurons in vivo Using Drosophila motor neurons, we show that parkin disruption generates an abnormal mitochondrial network in cell bodies in vivo and reduces the number of axonal mitochondria without producing any defects in their axonal transport, morphology, or metabolic state. Furthermore, while cultured neurons display Parkin-dependent axonal mitophagy, we find this is vanishingly rare in vivo under normal physiological conditions. Thus, both the spatial distribution and mechanism of mitochondrial quality control in vivo differ substantially from those observed in vitro. PMID- 27413151 TI - Functional Imaging of Dentate Granule Cells in the Adult Mouse Hippocampus. AB - The hippocampal dentate gyrus is critically involved in learning and memory. However, methods for imaging the activity of its principal neurons, the dentate gyrus granule cells, are missing. Here we demonstrate chronic two-photon imaging of granule cell population activity in awake mice using a cortical window implant that leaves the hippocampal formation intact and does not lead to obvious alteration of animal behavior. Using virus delivery, we targeted expression of genetically encoded calcium indicators specifically to dentate gyrus granule cells. Calcium imaging of granule cell activity 600-800 MUm below the hippocampal surface was facilitated by using 1040 nm excitation of the red indicator R CaMP1.07, but was also achieved using the green indicator GCaMP6s. We found that the rate of calcium transients was increased during wakefulness relative to an extremely low rate during anesthesia; however, activity still remained sparse with, on average, approximately one event per 2-5 min per cell across the granule cell population. Comparing periods of running on a ladder wheel and periods of resting, we furthermore identified state-dependent differences in the active granule cell population, with some cells displaying highest activity level during running and others during resting. Typically, cells did not maintain a clear state preference in their activity pattern across days. Our approach opens new avenues to elucidate granule cell function, plasticity mechanisms, and network computation in the adult dentate gyrus. SIGNIFICANCE STATEMENT: We describe a technique that allows for chronic, functional imaging of dentate gyrus granule cells in awake, behaving mice in an intact hippocampal circuitry using genetically encoded calcium indicators. This novel approach enables the analyses of individual granule cell activity over time and provides a powerful tool to elucidate the mechanisms underlying structural and functional plasticity of the adult dentate gyrus. PMID- 27413152 TI - G2019S-LRRK2 Expression Augments alpha-Synuclein Sequestration into Inclusions in Neurons. AB - Pathologic inclusions define alpha-synucleinopathies that include Parkinson's disease (PD). The most common genetic cause of PD is the G2019S LRRK2 mutation that upregulates LRRK2 kinase activity. However, the interaction between alpha synuclein, LRRK2, and the formation of alpha-synuclein inclusions remains unclear. Here, we show that G2019S-LRRK2 expression, in both cultured neurons and dopaminergic neurons in the rat substantia nigra pars compact, increases the recruitment of endogenous alpha-synuclein into inclusions in response to alpha synuclein fibril exposure. This results from the expression of mutant G2019S LRRK2, as overexpression of WT-LRRK2 not only does not increase formation of inclusions but reduces their abundance. In addition, treatment of primary mouse neurons with LRRK2 kinase inhibitors, PF-06447475 and MLi-2, blocks G2019S-LRRK2 effects, suggesting that the G2019S-LRRK2 potentiation of inclusion formation depends on its kinase activity. Overexpression of G2019S-LRRK2 slightly increases, whereas WT-LRRK2 decreases, total levels of alpha-synuclein. Knockdown of total alpha-synuclein with potent antisense oligonucleotides substantially reduces inclusion formation in G2019S-LRRK2-expressing neurons, suggesting that LRRK2 influences alpha-synuclein inclusion formation by altering alpha-synuclein levels. These findings support the hypothesis that G2019S-LRRK2 may increase the progression of pathological alpha-synuclein inclusions after the initial formation of alpha-synuclein pathology by increasing a pool of alpha-synuclein that is more susceptible to forming inclusions. SIGNIFICANCE STATEMENT: alpha Synuclein inclusions are found in the brains of patients with many different neurodegenerative diseases. Point mutation, duplication, or triplication of the alpha-synuclein gene can all cause Parkinson's disease (PD). The G2019S mutation in LRRK2 is the most common known genetic cause of PD. The interaction between G2019S-LRRK2 and alpha-synuclein may uncover new mechanisms and targets for neuroprotection. Here, we show that expression of G2019S-LRRK2 increases alpha synuclein mobility and enhances aggregation of alpha-synuclein in primary cultured neurons and in dopaminergic neurons of the substantia nigra pars compacta, a susceptible brain region in PD. Potent LRRK2 kinase inhibitors, which are being developed for clinical use, block the increased alpha-synuclein aggregation in G2019S-LRRK2-expressing neurons. These results demonstrate that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of PD-associated pathology. PMID- 27413153 TI - Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke. AB - Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome. SIGNIFICANCE STATEMENT: We have identified a bidirectional communication along the brain-gut microbiota immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury. PMID- 27413154 TI - A New Glucocerebrosidase Chaperone Reduces alpha-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism. AB - Among the known genetic risk factors for Parkinson disease, mutations in GBA1, the gene responsible for the lysosomal disorder Gaucher disease, are the most common. This genetic link has directed attention to the role of the lysosome in the pathogenesis of parkinsonism. To study how glucocerebrosidase impacts parkinsonism and to evaluate new therapeutics, we generated induced human pluripotent stem cells from four patients with Type 1 (non-neuronopathic) Gaucher disease, two with and two without parkinsonism, and one patient with Type 2 (acute neuronopathic) Gaucher disease, and differentiated them into macrophages and dopaminergic neurons. These cells exhibited decreased glucocerebrosidase activity and stored the glycolipid substrates glucosylceramide and glucosylsphingosine, demonstrating their similarity to patients with Gaucher disease. Dopaminergic neurons from patients with Type 2 and Type 1 Gaucher disease with parkinsonism had reduced dopamine storage and dopamine transporter reuptake. Levels of alpha-synuclein, a protein present as aggregates in Parkinson disease and related synucleinopathies, were selectively elevated in neurons from the patients with parkinsonism or Type 2 Gaucher disease. The cells were then treated with NCGC607, a small-molecule noninhibitory chaperone of glucocerebrosidase identified by high-throughput screening and medicinal chemistry structure optimization. This compound successfully chaperoned the mutant enzyme, restored glucocerebrosidase activity and protein levels, and reduced glycolipid storage in both iPSC-derived macrophages and dopaminergic neurons, indicating its potential for treating neuronopathic Gaucher disease. In addition, NCGC607 reduced alpha-synuclein levels in dopaminergic neurons from the patients with parkinsonism, suggesting that noninhibitory small-molecule chaperones of glucocerebrosidase may prove useful for the treatment of Parkinson disease. SIGNIFICANCE STATEMENT: Because GBA1 mutations are the most common genetic risk factor for Parkinson disease, dopaminergic neurons were generated from iPSC lines derived from patients with Gaucher disease with and without parkinsonism. These cells exhibit deficient enzymatic activity, reduced lysosomal glucocerebrosidase levels, and storage of glucosylceramide and glucosylsphingosine. Lines generated from the patients with parkinsonism demonstrated elevated levels of alpha-synuclein. To reverse the observed phenotype, the neurons were treated with a novel noninhibitory glucocerebrosidase chaperone, which successfully restored glucocerebrosidase activity and protein levels and reduced glycolipid storage. In addition, the small-molecule chaperone reduced alpha-synuclein levels in dopaminergic neurons, indicating that chaperoning glucocerebrosidase to the lysosome may provide a novel therapeutic strategy for both Parkinson disease and neuronopathic forms of Gaucher disease. PMID- 27413155 TI - Dynamic Structure of Neural Variability in the Cortical Representation of Speech Sounds. AB - Accurate sensory discrimination is commonly believed to require precise representations in the nervous system; however, neural stimulus responses can be highly variable, even to identical stimuli. Recent studies suggest that cortical response variability decreases during stimulus processing, but the implications of such effects on stimulus discrimination are unclear. To address this, we examined electrocorticographic cortical field potential recordings from the human nonprimary auditory cortex (superior temporal gyrus) while subjects listened to speech syllables. Compared with a prestimulus baseline, activation variability decreased upon stimulus onset, similar to findings from microelectrode recordings in animal studies. We found that this decrease was simultaneous with encoding and spatially specific for those electrodes that most strongly discriminated speech sounds. We also found that variability was predominantly reduced in a correlated subspace across electrodes. We then compared signal and variability (noise) correlations and found that noise correlations reduce more for electrodes with strong signal correlations. Furthermore, we found that this decrease in variability is strongest in the high gamma band, which correlates with firing rate response. Together, these findings indicate that the structure of single trial response variability is shaped to enhance discriminability despite non stimulus-related noise. SIGNIFICANCE STATEMENT: Cortical responses can be highly variable to auditory speech sounds. Despite this, sensory perception can be remarkably stable. Here, we recorded from the human superior temporal gyrus, a high-order auditory cortex, and studied the changes in the cortical representation of speech stimuli across multiple repetitions. We found that neural variability is reduced upon stimulus onset across electrodes that encode speech sounds. PMID- 27413156 TI - Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1. AB - Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. SIGNIFICANCE STATEMENT: This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly. Second, the results demonstrate that a synaptogenic process that controls excitatory inputs to both pyramidal neurons and interneurons can balance excitation and inhibition. Specifically, the study reveals that hippocampal CA3 connectivity is modulated by the synapse-organizing adhesion protein SynCAM 1 and identifies a novel, SynCAM 1 dependent mechanism that controls excitatory inputs onto parvalbumin-positive interneurons. This enables SynCAM 1 to regulate feedforward inhibition and set network excitability. Further, we show that diffusion tensor imaging is sensitive to these cellular refinements affecting neuronal connectivity. PMID- 27413157 TI - Time Cells in Hippocampal Area CA3. AB - Studies on time cells in the hippocampus have so far focused on area CA1 in animals performing memory tasks. Some studies have suggested that temporal processing within the hippocampus may be exclusive to CA1 and CA2, but not CA3, and may occur only under strong demands for memory. Here we examined the temporal and spatial coding properties of CA3 and CA1 neurons in rats performing a maze task that demanded working memory and a control task with no explicit working memory demand. In the memory demanding task, CA3 cells exhibited robust temporal modulation similar to the pattern of time cell activity in CA1, and the same populations of cells also exhibited typical place coding patterns in the same task. Furthermore, the temporal and spatial coding patterns of CA1 and CA3 were equivalently robust when animals performed a simplified version of the task that made no demands on working memory. However, time and place coding did differ in that the resolution of temporal coding decreased over time within the delay interval, whereas the resolution of place coding was not systematically affected by distance along the track. These findings support the view that CA1 and CA3 both participate in encoding the temporal and spatial organization of ongoing experience. SIGNIFICANCE STATEMENT: Hippocampal "time cells" that fire at specific moments in a temporally structured memory task have so far been observed only in area CA1, and some studies have suggested that temporal coding within the hippocampus is exclusive to CA1. Here we describe time cells also in CA3, and time cells in both areas are observed even without working memory demands, similar to place cells in these areas. However, unlike equivalent spatial coding along a path, temporal coding is nonlinear, with greater temporal resolution earlier than later in temporally structured experiences. These observations reveal both similarities and differences in temporal and spatial coding within the hippocampus of importance to understanding how these features of memory are represented in the hippocampus. PMID- 27413158 TI - Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission. AB - The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ~50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7-12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ~4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. SIGNIFICANCE STATEMENT: Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with anticonvulsant medication, surgical resection, and/or nerve/brain electrode stimulation. However, there are examples in humans of epilepsy with recurrent, unprovoked seizures remitting without any intervention. While elucidating how recurrent, unprovoked seizures develop is critical for understanding epileptogenesis, an understanding of how and why recurrent, unprovoked seizures remit may further our understanding and treatment of epilepsy. Here, we describe a new model of recurrent, unprovoked spontaneous seizures in which the occurrence of spontaneous seizures naturally remits over time without any therapeutic intervention. PMID- 27413159 TI - Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK. AB - Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKalpha increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKalpha in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL. SIGNIFICANCE STATEMENT: Our results demonstrate for the first time that the activation of AMP activated protein kinase (AMPK) alpha in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKalpha1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy. PMID- 27413160 TI - Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli. AB - Voltage-gated sodium channel Nav1.7 is a central player in human pain. Mutations in Nav1.7 produce several pain syndromes, including inherited erythromelalgia (IEM), a disorder in which gain-of-function mutations render dorsal root ganglia (DRG) neurons hyperexcitable. Although patients with IEM suffer from episodes of intense burning pain triggered by warmth, the effects of increased temperature on DRG neurons expressing mutant Nav1.7 channels have not been well documented. Here, using structural modeling, voltage-clamp, current-clamp, and multielectrode array recordings, we have studied a newly identified Nav1.7 mutation, Ala1632Gly, from a multigeneration family with IEM. Structural modeling suggests that Ala1632 is a molecular hinge and that the Ala1632Gly mutation may affect channel gating. Voltage-clamp recordings revealed that the Nav1.7-A1632G mutation hyperpolarizes activation and depolarizes fast-inactivation, both gain-of-function attributes at the channel level. Whole-cell current-clamp recordings demonstrated increased spontaneous firing, lower current threshold, and enhanced evoked firing in rat DRG neurons expressing Nav1.7-A1632G mutant channels. Multielectrode array recordings further revealed that intact rat DRG neurons expressing Nav1.7-A1632G mutant channels are more active than those expressing Nav1.7 WT channels. We also showed that physiologically relevant thermal stimuli markedly increase the mean firing frequencies and the number of active rat DRG neurons expressing Nav1.7 A1632G mutant channels, whereas the same thermal stimuli only increase these parameters slightly in rat DRG neurons expressing Nav1.7 WT channels. The response of DRG neurons expressing Nav1.7-A1632G mutant channels upon increase in temperature suggests a cellular basis for warmth-triggered pain in IEM. SIGNIFICANCE STATEMENT: Inherited erythromelalgia (IEM), a severe pain syndrome characterized by episodes of intense burning pain triggered by warmth, is caused by mutations in sodium channel Nav1.7, which are preferentially expressed in sensory and sympathetic neurons. More than 20 gain-of-function Nav1.7 mutations have been identified from IEM patients, but the question of how warmth triggers episodes of pain in IEM has not been well addressed. Combining multielectrode array, voltage-clamp, and current-clamp recordings, we assessed a newly identified IEM mutation (Nav1.7-A1632G) from a multigeneration family. Our data demonstrate gain-of-function attributes at the channel level and differential effects of physiologically relevant thermal stimuli on the excitability of DRG neurons expressing mutant and WT Nav1.7 channels, suggesting a cellular mechanism for warmth-triggered pain episodes in IEM patients. PMID- 27413161 TI - Attention Increases Spike Count Correlations between Visual Cortical Areas. AB - Visual attention, which improves perception of attended locations or objects, has long been known to affect many aspects of the responses of neuronal populations in visual cortex. There are two nonmutually exclusive hypotheses concerning the neuronal mechanisms that underlie these perceptual improvements. The first hypothesis, that attention improves the information encoded by a population of neurons in a particular cortical area, has considerable physiological support. The second hypothesis is that attention improves perception by selectively communicating relevant visual information. This idea has been tested primarily by measuring interactions between neurons on very short timescales, which are mathematically nearly independent of neuronal interactions on longer timescales. We tested the hypothesis that attention changes the way visual information is communicated between cortical areas on longer timescales by recording simultaneously from neurons in primary visual cortex (V1) and the middle temporal area (MT) in rhesus monkeys. We used two independent and complementary approaches. Our correlative experiment showed that attention increases the trial to-trial response variability that is shared between the two areas. In our causal experiment, we electrically microstimulated V1 and found that attention increased the effect of stimulation on MT responses. Together, our results suggest that attention affects both the way visual stimuli are encoded within a cortical area and the extent to which visual information is communicated between areas on behaviorally relevant timescales. SIGNIFICANCE STATEMENT: Visual attention dramatically improves the perception of attended stimuli. Attention has long been thought to act by selecting relevant visual information for further processing. It has been hypothesized that this selection is accomplished by increasing communication between neurons that encode attended information in different cortical areas. We recorded simultaneously from neurons in primary visual cortex and the middle temporal area while rhesus monkeys performed an attention task. We found that attention increased shared variability between neurons in the two areas and that attention increased the effect of microstimulation in V1 on the firing rates of MT neurons. Our results provide support for the hypothesis that attention increases communication between neurons in different brain areas on behaviorally relevant timescales. PMID- 27413164 TI - The Relationship Between Mutuality, Filial Piety, and Depression in Family Caregivers in China. AB - : Purpose Caregiving to parent stroke survivors in China is increasing and adult child-parent relationships are being challenged. The purpose of this study was to explore whether mutuality and filial piety have a protective role against caregiver depression. Design A cross-sectional correlational study was conducted with a nonproportional quota sample of 126 caregivers. Surveys were conducted at hospitals or in homes using structured questionnaires: the 15-item Mutuality Scale, the 4-item Filial Attitude Scale, the 9-item Filial Behavior Scale, and the 10-item Center for Epidemiological Studies Depression Scale. RESULTS: Higher mutuality and stronger filial attitudes were significantly associated with less caregiver depression after the covariates were controlled. Mutuality explained 5.5% (p < .01) and filial attitude explained 4.6% (p < .01) of the variance in caregiver depression. Conclusion Mutuality and filial attitude may be protective factors against caregiver depression. Implications for Practice Supportive strategies can be implemented to enhance mutuality and filial attitude. PMID- 27413162 TI - Diverse Representations of Olfactory Information in Centrifugal Feedback Projections. AB - Although feedback or centrifugal projections from higher processing centers of the brain to peripheral regions have long been known to play essential functional roles, the anatomical organization of these connections remains largely unknown. Using a virus-based retrograde labeling strategy and 3D whole-brain reconstruction methods, we mapped the spatial organization of centrifugal projections from two olfactory cortical areas, the anterior olfactory nucleus (AON) and the piriform cortex, to the granule cell layer of the main olfactory bulb in the mouse. Both regions are major recipients of information from the bulb and are the largest sources of feedback to the bulb, collectively constituting circuits essential for olfactory coding and olfactory behavior. We found that, although ipsilateral inputs from the AON were uniformly distributed, feedback from the contralateral AON had a strong ventral bias. In addition, we observed that centrifugally projecting neurons were spatially clustered in the piriform cortex, in contrast to the distributed feedforward axonal inputs that these cells receive from the principal neurons of the bulb. Therefore, information carried from the bulb to higher processing structures by anatomically stereotypic projections is likely relayed back to the bulb by organizationally distinct feedback projections that may reflect different coding strategies and therefore different functional roles. SIGNIFICANCE STATEMENT: Principles of anatomical organization, sometimes instantiated as "maps" in the mammalian brain, have provided key insights into the structure and function of circuits in sensory systems. Generally, these characterizations focus on projections from early sensory processing areas to higher processing structures despite considerable evidence that feedback or centrifugal projections often constitute major conduits of information flow. Our results identify structure in the organization of centrifugal feedback projections to the olfactory bulb that is fundamentally different from the organization of feedforward circuits. Our study suggests that understanding computations performed in the olfactory bulb, and more generally in the olfactory system, requires understanding interactions between feedforward and feedback "maps" both structurally and functionally. PMID- 27413163 TI - Stimulus Dependence of Correlated Variability across Cortical Areas. AB - The way that correlated trial-to-trial variability between pairs of neurons in the same brain area (termed spike count or noise correlation, rSC) depends on stimulus or task conditions can constrain models of cortical circuits and of the computations performed by networks of neurons (Cohen and Kohn, 2011). In visual cortex, rSC tends not to depend on stimulus properties (Kohn and Smith, 2005; Huang and Lisberger, 2009) but does depend on cognitive factors like visual attention (Cohen and Maunsell, 2009; Mitchell et al., 2009). However, neurons across visual areas respond to any visual stimulus or contribute to any perceptual decision, and the way that information from multiple areas is combined to guide perception is unknown. To gain insight into these issues, we recorded simultaneously from neurons in two areas of visual cortex (primary visual cortex, V1, and the middle temporal area, MT) while rhesus monkeys viewed different visual stimuli in different attention conditions. We found that correlations between neurons in different areas depend on stimulus and attention conditions in very different ways than do correlations within an area. Correlations across, but not within, areas depend on stimulus direction and the presence of a second stimulus, and attention has opposite effects on correlations within and across areas. This observed pattern of cross-area correlations is predicted by a normalization model where MT units sum V1 inputs that are passed through a divisive nonlinearity. Together, our results provide insight into how neurons in different areas interact and constrain models of the neural computations performed across cortical areas. SIGNIFICANCE STATEMENT: Correlations in the responses of pairs of neurons within the same cortical area have been a subject of growing interest in systems neuroscience. However, correlated variability between different cortical areas is likely just as important. We recorded simultaneously from neurons in primary visual cortex and the middle temporal area while rhesus monkeys viewed different visual stimuli in different attention conditions. We found that correlations between neurons in different areas depend on stimulus and attention conditions in very different ways than do correlations within an area. The observed pattern of cross-area correlations was predicted by a simple normalization model. Our results provide insight into how neurons in different areas interact and constrain models of the neural computations performed across cortical areas. PMID- 27413165 TI - Quantitative EEG parameters correlate with the progression of human prion diseases. AB - BACKGROUND: Prion diseases are universally fatal and often rapidly progressive neurodegenerative diseases. EEG has long been used in the diagnosis of sporadic Creutzfeldt-Jakob disease; however, the characteristic waveforms do not occur in all types of prion diseases. Here, we re-evaluate the utility of EEG by focusing on the development of biomarkers. We test whether abnormal quantitative EEG parameters can be used to measure disease progression in prion diseases or predict disease onset in healthy individuals at risk of disease. METHODS: In the National Prion Monitoring Cohort study, we did quantitative encephalography on 301 occasions in 29 healthy controls and 67 patients with prion disease. The patients had either inherited prion disease or sporadic Creutzfeldt-Jakob disease. We computed the main background frequency, the alpha and theta power and the alpha/theta power ratio, then averaged these within 5 electrode groups. These measurements were then compared among participant groups and correlated with functional and cognitive scores cross-sectionally and longitudinally. RESULTS: We found lower main background frequency, alpha power and alpha/theta power ratio and higher theta power in patients compared to control participants. The main background frequency, the power in the alpha band and the alpha/theta power ratio also differed in a consistent way among the patient groups. Moreover, the main background frequency and the alpha/theta power ratio correlated significantly with functional and cognitive scores. Longitudinally, change in these parameters also showed significant correlation with the change in clinical and cognitive scores. CONCLUSIONS: Our findings support the use of quantitative EEG to follow the progression of prion disease, with potential to help evaluate the treatment effects in future clinical-trials. PMID- 27413166 TI - Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non-Small Cell Lung Cancer Cells. AB - Non-small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non-small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non-small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle-associated proteins by Western blot analysis and found immature colon carcinoma transcript 1 -mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non-small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non-small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non-small cell lung cancer. PMID- 27413167 TI - Influence of intracellular Ca2+ and alternative splicing on the pharmacological profile of ANO1 channels. AB - Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel expressed in many types of cells. Splice variants of ANO1 have been shown to influence the biophysical properties of conductance. It has been suggested that several new antagonists of ANO1 with relatively high affinity and selectivity might be useful for experimental and, potentially, therapeutic purposes. We investigated the effects of intracellular Ca(2+) concentration ([Ca(2+)]i) at 100-1,000 nM, a concentration range that might be achieved in cells during physiological activation of ANO1 channels, on blockade of ANO1 channels expressed in HEK-293 cells. Whole cell and excised patch configurations of the patch-clamp technique were used to perform tests on a variety of naturally occurring splice variants of ANO1. Blockade of ANO1 currents with aminophenylthiazole (T16Ainh-A01) was highly dependent on [Ca(2+)]i Increasing [Ca(2+)]i reduced the potency of this blocker. Similar Ca(2+)-dependent effects were also observed with benzbromarone. Experiments on excised, inside-out patches showed that the diminished potency of the blockers caused by intracellular Ca(2+) might involve a competitive interaction for a common binding site or repulsion of the blocking drugs by electrostatic forces at the cytoplasmic surface of the channels. The degree of interaction between the channel blockers and [Ca(2+)]i depends on the splice variant expressed. These experiments demonstrate that the efficacy of ANO1 antagonists depends on [Ca(2+)]i, suggesting a need for caution when ANO1 blockers are used to determine the role of ANO1 in physiological functions and in their use as therapeutic agents. PMID- 27413168 TI - TNF-alpha augments RANKL-dependent intestinal M cell differentiation in enteroid cultures. AB - Microfold (M) cells are phagocytic intestinal epithelial cells in the follicle associated epithelium of Peyer's patches that transport particulate antigens from the gut lumen into the subepithelial dome. Differentiation of M cells from epithelial stem cells in intestinal crypts requires the cytokine receptor activator of NF-kappaB ligand (RANKL) and the transcription factor Spi-B. We used three-dimensional enteroid cultures established with small intestinal crypts from mice as a model system to investigate signaling pathways involved in M cell differentiation and the influence of other cytokines on RANKL-induced M cell differentiation. Addition of RANKL to enteroids induced expression of multiple M cell-associated genes, including Spib, Ccl9 [chemokine (C-C motif) ligand 9], Tnfaip2 (TNF-alpha-induced protein 2), Anxa5 (annexin A5), and Marcksl1 (myristoylated alanine-rich protein kinase C substrate) in 1 day. The mature M cell marker glycoprotein 2 (Gp2) was strongly induced by 3 days and expressed by 11% of cells in enteroids. The noncanonical NF-kappaB pathway was required for RANKL-induced M cell differentiation in enteroids, as addition of RANKL to enteroids from mice with a null mutation in the mitogen-activated protein kinase kinase kinase 14 (Map3k14) gene encoding NF-kappaB-inducing kinase failed to induce M cell-associated genes. While the cytokine TNF-alpha alone had little, if any, effect on expression of M cell-associated genes, addition of TNF-alpha to RANKL consistently resulted in three- to sixfold higher levels of multiple M cell associated genes than RANKL alone. One contributing mechanism is the rapid induction by TNF-alpha of Relb and Nfkb2 (NF-kappaB subunit 2), genes encoding the two subunits of the noncanonical NF-kappaB heterodimer. We conclude that endogenous activators of canonical NF-kappaB signaling present in the gut associated lymphoid tissue microenvironment, including TNF-alpha, can play a supportive role in the RANKL-dependent differentiation of M cells in the follicle associated epithelium. PMID- 27413169 TI - Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD emphysema exacerbations and pathogenesis. AB - Cigarette-smoke (CS) exposure and aging are the leading causes of chronic obstructive pulmonary disease (COPD)-emphysema development, although the molecular mechanism that mediates disease pathogenesis remains poorly understood. Our objective was to investigate the impact of CS exposure and aging on autophagy and the pathophysiological changes associated with lung aging (senescence) and emphysema progression. Beas2b cells, C57BL/6 mice, and human (GOLD 0-IV) lung tissues were used to determine the central mechanism involved in CS/age-related COPD-emphysema pathogenesis. Beas2b cells and murine lungs exposed to cigarette smoke extract (CSE)/CS showed a significant ( P < 0.05) accumulation of poly ubiquitinated proteins and impaired autophagy marker, p62, in aggresome bodies. Moreover, treatment with the autophagy-inducing antioxidant drug cysteamine significantly ( P < 0.001) decreased CSE/CS-induced aggresome bodies. We also found a significant ( P < 0.001) increase in levels of aggresome bodies in the lungs of smokers and COPD subjects in comparison to nonsmoker controls. Furthermore, the presence and levels of aggresome bodies statistically correlated with severity of emphysema and alveolar senescence. In addition to CS exposure, lungs from old mice also showed accumulation of aggresome bodies, suggesting this as a common mechanism to initiate cellular senescence and emphysema. Additionally, Beas2b cells and murine lungs exposed to CSE/CS showed cellular apoptosis and senescence, which were both controlled by cysteamine treatment. In parallel, we evaluated the impact of CS on pulmonary exacerbation, using mice exposed to CS and/or infected with Pseudomonas aeruginosa ( Pa), and confirmed cysteamine's potential as an autophagy-inducing antibacterial drug, based on its ability to control CS-induced pulmonary exacerbation ( Pa-bacterial counts) and resulting inflammation. CS induced autophagy impairment accelerates lung aging and COPD-emphysema exacerbations and pathogenesis. PMID- 27413170 TI - Biotin deficiency enhances the inflammatory response of human dendritic cells. AB - The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-alpha, IL-12p40, IL-23, and IL-1beta compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-gamma and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency. PMID- 27413171 TI - Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction. AB - We have previously demonstrated that low-energy extracorporeal cardiac shock wave (SW) therapy improves myocardial ischemia through enhanced myocardial angiogenesis in a porcine model of chronic myocardial ischemia and in patients with refractory angina pectoris. However, the detailed molecular mechanisms for the SW-induced angiogenesis remain unclear. In this study, we thus examined the effects of SW irradiation on intracellular signaling pathways in vitro. Cultured human umbilical vein endothelial cells (HUVECs) were treated with 800 shots of low-energy SW (1 Hz at an energy level of 0.03 mJ/mm(2)). The SW therapy significantly upregulated mRNA expression and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The SW therapy also enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and Akt. Furthermore, the SW therapy enhanced phosphorylation of caveolin-1 and the expression of HUTS-4 that represents beta1-integrin activity. These results suggest that caveolin-1 and beta1-integrin are involved in the SW-induced activation of angiogenic signaling pathways. To further examine the signaling pathways involved in the SW-induced angiogenesis, HUVECs were transfected with siRNA of either beta1-integrin or caveolin-1. Knockdown of either caveolin-1 or beta1-integrin suppressed the SW-induced phosphorylation of Erk1/2 and Akt and upregulation of VEGF and eNOS. Knockdown of either caveolin-1 or beta1-integrin also suppressed SW-induced enhancement of HUVEC migration in scratch assay. These results suggest that activation of mechanosensors on cell membranes, such as caveolin-1 and beta1-integrin, and subsequent phosphorylation of Erk and Akt may play pivotal roles in the SW-induced angiogenesis. PMID- 27413172 TI - A high-resolution method for assessing cellular oxidative phosphorylation efficiency: bringing mitochondrial bioenergetics into focus. Focus on "Direct real-time quantification of mitochondrial oxidative phosphorylation efficiency in permeabilized skeletal muscle myofibers". PMID- 27413174 TI - Population Health: Considerations for School Health Research and Practice. PMID- 27413173 TI - Bortezomib alleviates experimental pulmonary hypertension by regulating intracellular calcium homeostasis in PASMCs. AB - The ubiquitin-proteasome system is considered to be the key regulator of protein degradation. Bortezomib (BTZ) is the first proteasome inhibitor approved by the US Food and Drug Administration for treatment of relapsed multiple myeloma and mantle cell lymphoma. Recently, BTZ treatment was reported to inhibit right ventricular hypertrophy and vascular remodeling in hypoxia-exposed and monocrotaline-injected rats. However, the underlying mechanisms remain poorly understood. We previously confirmed that hypoxia-elevated basal intracellular Ca(2+) concentration ([Ca(2+)]i) and store-operated Ca(2+) entry (SOCE) in pulmonary artery smooth muscle cells (PASMCs) are involved in pulmonary vascular remodeling. In this study we aim to determine whether BTZ attenuates the hypoxia induced elevation of [Ca(2+)] in PASMCs and the signaling pathway involved in this mechanism. Our results showed that 1) in hypoxia- and monocrotaline-induced rat pulmonary hypertension (PH) models, BTZ markedly attenuated the development and progression of PH, 2) BTZ inhibited the hypoxia-induced increase in cell proliferation, basal [Ca(2+)]i, and SOCE in PASMCs, and 3) BTZ significantly normalized the hypoxia-upregulated expression of hypoxia-inducible factor-1alpha, bone morphogenetic protein 4, canonical transient receptor potential isoforms 1 and 6, and the hypoxia-downregulated expression of peroxisome proliferator activated receptor-gamma in rat distal pulmonary arteries and PASMCs. These results indicate that BTZ exerts its protective role in the development of PH potentially by inhibiting the canonical transient receptor potential-SOCE [Ca(2+)]i signaling axis in PASMCs. PMID- 27413175 TI - Total intravenous anaesthesia using propofol and sufentanil allows controlled long-term ventilation in rabbits without neuromuscular blocking agents. AB - The aim of this study was to evaluate a total intravenous anaesthesia (TIVA) protocol using propofol and sufentanil without neuromuscular blocking agents (NBAs) for a non-recovery lung pathology study in rabbits including 10 h of pressure-controlled ventilation. TIVA was started with 20 mg/kg/h propofol and 0.5 ug/kg/h sufentanil. The depth of anaesthesia was assessed by reflex testing and monitoring of spontaneous movements or respiratory efforts. Vital parameters were monitored to assess the effects of the TIVA protocol. The infusion rates were increased whenever reflex testing indicated inadequate depth of anaesthesia, and were reduced when vital parameters indicated unnecessarily deep levels. Median infusion rates of 35 mg/kg/h propofol and 2.0 ug/kg/h sufentanil were needed to ensure an adequate depth of anaesthesia. This protocol suppressed spontaneous movements, breathing and palpebral reflexes, but was unable to suppress corneal and pedal withdrawal reflexes. Since significant drops in arterial blood pressure (ABP) were observed and the animals were not exposed to painful procedures, positive corneal and pedal withdrawal reflexes were tolerated. In conclusion, propofol and sufentanil is a suitable combination for long-term anaesthesia in non-recovery lung pathology models in rabbits without painful procedures. ABP must be monitored carefully because of the circulatory side-effects, but it is an inappropriate surrogate marker for depth of anaesthesia. Due to the lack of neuromuscular blockade this TIVA protocol allows the adjustment of infusion rates based on reflex testing. The resulting decreased risk of unnoticed awareness is a decisive refinement in anaesthesia for similar studies including long-term mechanical ventilation in rabbits. PMID- 27413176 TI - Classic Spotlight: to the Periplasm and Beyond-Protein Secretion in Escherichia coli. PMID- 27413177 TI - Classic Spotlight: Studies on the Low-Calcium Response of Yersinia pestis Reveal the Secrets of Plague Pathogenesis. PMID- 27413180 TI - Letter to the editor: Comments on Cornachione et al. (2016): "The increase in non cross-bridge forces after stretch of activated striated muscle is related to titin isoforms". PMID- 27413181 TI - Reply to "Letter to the editor: Comments on Cornachione et al. (2016): "The increase in non-cross-bridge forces after stretch of activated striated muscle is related to titin isoforms". PMID- 27413182 TI - The Structure of the Plakin Domain of Plectin Reveals an Extended Rod-like Shape. AB - Plakins are large multi-domain proteins that interconnect cytoskeletal structures. Plectin is a prototypical plakin that tethers intermediate filaments to membrane-associated complexes. Most plakins contain a plakin domain formed by up to nine spectrin repeats (SR1-SR9) and an SH3 domain. The plakin domains of plectin and other plakins harbor binding sites for junctional proteins. We have combined x-ray crystallography with small angle x-ray scattering (SAXS) to elucidate the structure of the plakin domain of plectin, extending our previous analysis of the SR1 to SR5 region. Two crystal structures of the SR5-SR6 region allowed us to characterize its uniquely wide inter-repeat conformational variability. We also report the crystal structures of the SR7-SR8 region, refined to 1.8 A, and the SR7-SR9 at lower resolution. The SR7-SR9 region, which is conserved in all other plakin domains, forms a rigid segment stabilized by uniquely extensive inter-repeat contacts mediated by unusually long helices in SR8 and SR9. Using SAXS we show that in solution the SR3-SR6 and SR7-SR9 regions are rod-like segments and that SR3-SR9 of plectin has an extended shape with a small central kink. Other plakins, such as bullous pemphigoid antigen 1 and microtubule and actin cross-linking factor 1, are likely to have similar extended plakin domains. In contrast, desmoplakin has a two-segment structure with a central flexible hinge. The continuous versus segmented structures of the plakin domains of plectin and desmoplakin give insight into how different plakins might respond to tension and transmit mechanical signals. PMID- 27413183 TI - Contributions of the Lectin and Polypeptide Binding Sites of Calreticulin to Its Chaperone Functions in Vitro and in Cells. AB - Calreticulin is a lectin chaperone of the endoplasmic reticulum that interacts with newly synthesized glycoproteins by binding to Glc1Man9GlcNAc2 oligosaccharides as well as to the polypeptide chain. In vitro, the latter interaction potently suppresses the aggregation of various non-glycosylated proteins. Although the lectin-oligosaccharide association is well understood, the polypeptide-based interaction is more controversial because the binding site on calreticulin has not been identified, and its significance in the biogenesis of glycoproteins in cells remains unknown. In this study, we identified the polypeptide binding site responsible for the in vitro aggregation suppression function by mutating four candidate hydrophobic surface patches. Mutations in only one patch, P19K/I21E and Y22K/F84E, impaired the ability of calreticulin to suppress the thermally induced aggregation of non-glycosylated firefly luciferase. These mutants also failed to bind several hydrophobic peptides that act as substrate mimetics and compete in the luciferase aggregation suppression assay. To assess the relative contributions of the glycan-dependent and independent interactions in living cells, we expressed lectin-deficient, polypeptide binding-deficient, and doubly deficient calreticulin constructs in calreticulin-negative cells and monitored the effects on the biogenesis of MHC class I molecules, the solubility of mutant forms of alpha1-antitrypsin, and interactions with newly synthesized glycoproteins. In all cases, we observed a profound impairment in calreticulin function when its lectin site was inactivated. Remarkably, inactivation of the polypeptide binding site had little impact. These findings indicate that the lectin-based mode of client interaction is the predominant contributor to the chaperone functions of calreticulin within the endoplasmic reticulum. PMID- 27413186 TI - Corrigendum. PMID- 27413184 TI - AMP-activated Protein Kinase Up-regulates Mitogen-activated Protein (MAP) Kinase interacting Serine/Threonine Kinase 1a-dependent Phosphorylation of Eukaryotic Translation Initiation Factor 4E. AB - AMP-activated protein kinase (AMPK) is a molecular energy sensor that acts to sustain cellular energy balance. Although AMPK is implicated in the regulation of a multitude of ATP-dependent cellular processes, exactly how these processes are controlled by AMPK as well as the identity of AMPK targets and pathways continues to evolve. Here we identify MAP kinase-interacting serine/threonine protein kinase 1a (MNK1a) as a novel AMPK target. Specifically, we show AMPK-dependent Ser(353) phosphorylation of the human MNK1a isoform in cell-free and cellular systems. We show that AMPK and MNK1a physically interact and that in vivo MNK1a Ser(353) phosphorylation requires T-loop phosphorylation, in good agreement with a recently proposed structural regulatory model of MNK1a. Our data suggest a physiological role for MNK1a-Ser(353) phosphorylation in regulation of the MNK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo. PMID- 27413187 TI - Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children. AB - According to studies based on bacterial cultures of middle ear fluids, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis have been the most common pathogens in acute otitis media. However, bacterial culture can be affected by reduced viability or suboptimal growth of bacteria. PCR detects bacterial DNA from samples with greater sensitivity than culture. In the present study, we analyzed the middle ear pathogens with both conventional culture and semiquantitative real-time PCR in 90 middle ear fluid samples obtained from children aged 5 to 42 months during acute otitis media episodes. Samples were tested for the presence of S. pneumoniae, H. influenzae, M. catarrhalis, Alloiococcus otitidis, Staphylococcus aureus, and Pseudomonas aeruginosa One or more bacterial pathogens were detected in 42 (47%) samples with culture and in 69 (77%) samples with PCR. According to PCR analysis, M. catarrhalis results were positive in 42 (47%) samples, H. influenzae in 30 (33%), S. pneumoniae in 27 (30%), A. otitidis in 6 (6.7%), S. aureus in 5 (5.6%), and P. aeruginosa in 1 (1.1%). Multibacterial etiology was seen in 34 (38%) samples, and M. catarrhalis was detected in most (85%) of those cases. Fifteen signals for M. catarrhalis were strong, suggesting a highly probable etiological role of the pathogen. In conclusion, even though M. catarrhalis is often a part of mixed flora in acute otitis media, a considerable proportion of cases may be primarily attributable to this pathogen. PMID- 27413188 TI - Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India. AB - Aspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study analyzed the distribution and in vitro antifungal susceptibility profiles of rare Aspergillus species in clinical samples from patients with suspected aspergillosis in 8 medical centers in India. Further, a matrix-assisted laser desorption ionization time of flight mass spectrometry in-house database was developed to identify these clinically relevant Aspergillus species. beta-Tubulin and calmodulin gene sequencing identified 45 rare Aspergillus isolates to the species level, except for a solitary isolate. They included 23 less common Aspergillus species belonging to 12 sections, mainly in Circumdati, Nidulantes, Flavi, Terrei, Versicolores, Aspergillus, and Nigri Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) identified only 8 (38%) of the 23 rare Aspergillus isolates to the species level. Following the creation of an in house database with the remaining 14 species not available in the Bruker database, the MALDI-TOF MS identification rate increased to 95%. Overall, high MICs of >=2 MUg/ml were noted for amphotericin B in 29% of the rare Aspergillus species, followed by voriconazole in 20% and isavuconazole in 7%, whereas MICs of >0.5 MUg/ml for posaconazole were observed in 15% of the isolates. Regarding the clinical diagnoses in 45 patients with positive rare Aspergillus species cultures, 19 (42%) were regarded to represent colonization. In the remaining 26 patients, rare Aspergillus species were the etiologic agent of invasive, chronic, and allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, keratitis, and mycetoma. PMID- 27413189 TI - The First Fully Automated Molecular Diagnostic Panel for Meningitis and Encephalitis: How Well Does It Perform, and When Should It Be Used? AB - Rapid and accurate molecular diagnostic tests for the most common causes of infectious meningitis and encephalitis have the potential for high clinical impact. In this issue of the Journal of Clinical Microbiology, Leber et al. (J Clin Microbiol 54:2251-2261, 2016, http://dx.doi.org/10.1128/JCM.00730-16) report results from a large clinical study designed to prospectively assess the performance of the FilmArray meningitis/encephalitis panel compared to conventional methods. PMID- 27413190 TI - Coinfections of Zika and Chikungunya Viruses in Bahia, Brazil, Identified by Metagenomic Next-Generation Sequencing. AB - Metagenomic next-generation sequencing (mNGS) of samples from 15 patients with documented Zika virus (ZIKV) infection in Bahia, Brazil, from April 2015 to January 2016 identified coinfections with chikungunya virus (CHIKV) in 2 of 15 ZIKV-positive cases by PCR (13.3%). While generally nonspecific, the clinical presentation corresponding to these two CHIKV/ZIKV coinfections reflected infection by the virus present at a higher titer. Aside from CHIKV and ZIKV, coinfections of other viral pathogens were not detected. The mNGS approach is promising for differential diagnosis of acute febrile illness and identification of coinfections, although targeted arbovirus screening may be sufficient in the current ZIKV outbreak setting. PMID- 27413191 TI - Species Distribution and In Vitro Azole Susceptibility of Aspergillus Section Nigri Isolates from Clinical and Environmental Settings. AB - Aspergillus section Nigri includes species of interest for animal and human health, although studies on species distribution are limited to human cases. Data on the antifungal susceptibilities and the molecular mechanism of triazole resistance in strains belonging to this section are scant. Forty-two black Aspergillus strains from human patients (16 isolates), animals (14 isolates), and the environment (12 isolates) were molecularly characterized and their in vitro triazole susceptibilities investigated. Aspergillus tubingensis was isolated from humans, animals, and environmental settings, whereas Aspergillus awamori and Aspergillus niger were isolated exclusively from humans. Phylogenetic analyses of beta-tubulin and calmodulin gene sequences were concordant in differentiating A. tubingensis from A. awamori and A. niger Voriconazole and posaconazole (PSZ) were the most active triazoles. One A. tubingensis strain was resistant to itraconazole and PSZ and one A. niger strain to PSZ. Sequence analysis of the cyp51A gene revealed different sequence types within a species, and A. tubingensis strains were also phylogenetically distinct from A. awamori/A. niger strains according to the strain origin and susceptibility profile. Genetic analysis of the cyp51A sequences suggests that two nonsynonymous mutations resulting in amino acid substitutions in the CYP51A protein (changes of L to R at position 21 [L21R] and of Q to R at position 228 [Q228R]) might be involved in azole resistance. Though azole resistance in black Aspergillus isolates from animals and rural environments does not represent a threat to public health in Southern Italy, the use of triazoles in the clinical setting needs to better monitored. The cyp51A sequence is useful for the molecular identification of black Aspergillus, and point mutations in protein sequences could be responsible for azole resistance phenomena. PMID- 27413192 TI - Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of KPC-Producing Klebsiella pneumoniae. AB - We evaluated a real-time single-peak (11.109-Da) detection assay based on matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae Our results demonstrated that the 11.109-Da peak was detected in 88.2% of the KPC producers. Analysis of blaKPC-producing K. pneumoniae showed that the gene encoding the 11.109-Da protein was commonly (97.8%) associated with the Tn4401a isoform. PMID- 27413193 TI - Automatic Digital Analysis of Chromogenic Media for Vancomycin-Resistant Enterococcus Screens Using Copan WASPLab. AB - Vancomycin-resistant enterococci (VRE) are an important cause of health care acquired infections (HAIs). Studies have shown that active surveillance of high risk patients for VRE colonization can aid in reducing HAIs; however, these screens generate a significant cost to the laboratory and health care system. Digital imaging capable of differentiating negative and "nonnegative" chromogenic agar can reduce the labor cost of these screens and potentially improve patient care. In this study, we evaluated the performance of the WASPLab Chromogenic Detection Module (CDM) (Copan, Brescia, Italy) software to analyze VRE chromogenic agar and compared the results to technologist plate reading. Specimens collected at 3 laboratories were cultured using the WASPLab CDM and plated to each site's standard-of-care chromogenic media, which included Colorex VRE (BioMed Diagnostics, White City, OR) or Oxoid VRE (Oxoid, Basingstoke, United Kingdom). Digital images were scored using the CDM software after 24 or 40 h of growth, and all manual reading was performed using digital images on a high definition (HD) monitor. In total, 104,730 specimens were enrolled and automation agreed with manual analysis for 90.1% of all specimens tested, with sensitivity and specificity of 100% and 89.5%, respectively. Automation results were discordant for 10,348 specimens, and all discordant images were reviewed by a laboratory supervisor or director. After a second review, 499 specimens were identified as representing missed positive cultures falsely called negative by the technologist, 1,616 were identified as containing borderline color results (negative result but with no package insert color visible), and 8,234 specimens were identified as containing colorimetric pigmentation due to residual matrix from the specimen or yeast (Candida). Overall, the CDM was accurate at identifying negative VRE plates, which comprised 84% (87,973) of the specimens in this study. PMID- 27413194 TI - Culture-Independent Detection of Nontuberculous Mycobacteria in Clinical Respiratory Samples. AB - Culture-based detection of nontuberculous Mycobacteria (NTM) in respiratory samples is time consuming and can be subject to overgrowth by nonmycobacterial bacteria. We describe a single-reaction TaqMan quantitative PCR assay for the direct detection of NTM species in clinical samples that is specific, sensitive, and robust. PMID- 27413195 TI - Neisseria gonorrhoeae Bacterial DNA Load in the Pharynges and Saliva of Men Who Have Sex with Men. AB - Neisseria gonorrhoeae can be cultured in the saliva of individuals with pharyngeal gonorrhea. The aim of this study was to quantify the gonococcal bacterial DNA loads in the pharynges and saliva among men who have sex with men (MSM) with untreated pharyngeal gonorrhea. Untreated MSM who tested positive for pharyngeal gonorrhea by culture and returned for antibiotic treatment within 14 days at the Melbourne Sexual Health Centre between October 2014 and March 2015 were eligible for this study. The gonococcal bacterial DNA load was measured using real-time quantitative PCR. The median gonococcal bacterial DNA loads in the pharynges and saliva were calculated and compared to culture positivity using the Mann-Whitney U test. A total of 33 men were included in this study. The median gonococcal bacterial DNA load did not differ between the pharynges in men who were culture positive (2.5 * 10(5) copies/swab) and culture negative (2.9 * 10(4) copies/swab) (P = 0.166) and the saliva (culture positive, 2.2 * 10(5) copies/ml; culture negative, 2.7 * 10(5) copies/ml) (P = 0.499). The bacterial DNA load in the pharynges (P = 0.695) and saliva (P = 0.969) did not differ between who men returned for treatment within 7 days and those who returned 8 to 14 days later. Substantial gonococcal bacterial DNA loads were detected in both saliva and pharynges among MSM with pharyngeal gonorrhea. These findings suggest that gonorrhea can be transmitted via sexual practices involving exposure to saliva, such as oroanal practices (rimming) and saliva use as a lubricant for anal sex. PMID- 27413196 TI - The role of cGMP and its signaling pathways in kidney disease. AB - Cyclic nucleotide signal transduction pathways are an emerging research field in kidney disease. Activated cell surface receptors transduce their signals via intracellular second messengers such as cAMP and cGMP. There is increasing evidence that regulation of the cGMP-cGMP-dependent protein kinase 1 phosphodiesterase (cGMP-cGK1-PDE) signaling pathway may be renoprotective. Selective PDE5 inhibitors have shown potential in treating kidney fibrosis in patients with chronic kidney disease (CKD), via their downstream signaling, and these inhibitors also have known activity as antithrombotic and anticancer agents. This review gives an outline of the cGMP-cGK1-PDE signaling pathways and details the downstream signaling and regulatory functions that are modulated by cGK1 and PDE inhibitors with regard to antifibrotic, antithrombotic, and antitumor activity. Current evidence that supports the renoprotective effects of regulating cGMP-cGK1-PDE signaling is also summarized. Finally, the effects of icariin, a natural plant extract with PDE5 inhibitory function, are discussed. We conclude that regulation of cGMP-cGK1-PDE signaling might provide novel, therapeutic strategies for the worsening global public health problem of CKD. PMID- 27413197 TI - Mechanisms of connecting tubule glomerular feedback enhancement by aldosterone. AB - Connecting tubule glomerular feedback (CTGF) is a mechanism where an increase in sodium (Na) concentration in the connecting tubule (CNT) causes the afferent arteriole (Af-Art) to dilate. We recently reported that aldosterone within the CNT lumen enhances CTGF via a nongenomic effect involving GPR30 receptors and sodium/hydrogen exchanger (NHE), but the signaling pathways of this mechanism are unknown. We hypothesize that aldosterone enhances CTGF via cAMP/protein kinase A (PKA) pathway that activates protein kinase C (PKC) and stimulates superoxide (O2 ) production. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing the CNT luminal NaCl. We found that the main effect of aldosterone was to sensitize CTGF and we analyzed data by comparing NaCl concentration in the CNT perfusate needed to achieve half of the maximal response (EC50). During the control period, the NaCl concentration that elicited a half-maximal response (EC50) was 37.0 +/- 2.0 mmol/l; addition of aldosterone (10-8 mol/l) to the CNT lumen decreased EC50 to 19.3 +/- 1.3 mmol/l (P <= 0.001 vs. Control). The specific adenylyl cyclase inhibitor 2',3'-dideoxyadenosine (ddA; 2 * 10-4 mol/l) and the PKA inhibitor H-89 dihydrochloride hydrate (H-89; 2 * 10-6 mol/l) prevented the aldosterone effect. The selective PKC inhibitor GF109203X (10-8 mol/l) also prevented EC50 reduction caused by aldosterone. CNT intraluminal addition of O2- scavenger tempol (10-4 mol/l) blocked the aldosterone effect. We conclude that aldosterone inside the CNT lumen enhances CTGF via a cAMP/PKA/PKC pathway and stimulates O2- generation and this process may contribute to renal damage by increasing glomerular capillary pressure. PMID- 27413198 TI - Inhibition of mitochondrial complex-1 restores the downregulation of aquaporins in obstructive nephropathy. AB - Obstructive kidney disease is a common complication in the clinic. Downregulation of aquaporins (AQPs) in obstructed kidneys has been thought as a key factor leading to the polyuria and impairment of urine-concentrating capability after the release of kidney obstruction. The present study was to investigate the role of mitochondrial complex-1 in modulating AQPs in obstructive nephropathy. Following 7-day unilateral ureteral obstruction (UUO), AQP1, AQP2, AQP3, and vasopressin 2 (V2) receptor were remarkably reduced as determined by qRT-PCR and/or Western blotting. Notably, inhibition of mitochondrial complex-1 by rotenone markedly reversed the downregulation of AQP1, AQP2, AQP3, and V2 In contrast, AQP4 was not affected by kidney obstruction or rotenone treatment. In a separate study, rotenone also attenuated AQPs' downregulation after 48-h UUO. To study the potential mechanisms in mediating the rotenone effects on AQPs, we examined the regulation of the COX-2/microsomal prostaglandin E synthase (mPGES) 1/PGE2/EP pathway and found that COX-2, mPGES-1, and renal PGE2 content were all significantly elevated in obstructive kidneys, which was not affected by rotenone treatment. For EP receptors, EP2 and EP4 but not EP1 and EP3 were upregulated in obstructive kidneys. Importantly, rotenone strikingly suppressed EP1 and EP4 but not EP2 and EP3 receptors. However, treatment of EP1 antagonist SC-51322 could not affect AQPs' reduction in obstructed kidneys. Collectively, these findings suggested an important role of mitochondrial dysfunction in modulating AQPs and V2 receptor in obstructive nephropathy possibly via prostaglandin-independent mechanisms. PMID- 27413199 TI - Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development. AB - Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation. In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg.kg(-1).day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria. Stereological quantification showed a significant reduction in total length (386 +/- 13 vs. 219 +/- 16 m), surface area, and volume of medullary microvessels. Vascular bundle architecture was unaffected. ANG II-AT1A/1B (-/-) mice kidneys displayed poorly defined vasa recta bundles whereas mice with collecting duct principal cell-specific AT1A deletion displayed no medullary microvascular phenotype. In conclusion, VEGFR2 signaling during postnatal development is necessary for expansion of the renal medullary microcirculation but not structural patterning of the vasa recta bundles, which occurs through an AT1-mediated mechanism. PMID- 27413200 TI - SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone. AB - We examined renal Na and K transporters in mice with deletions in the gene encoding the aldosterone-induced protein SGK1. The knockout mice were hyperkalemic, and had altered expression of the subunits of the epithelial Na channel (ENaC). The kidneys showed decreased expression of the cleaved forms of the gammaENaC subunit, and the fully glycosylated form of the betaENaC subunits when animals were fed a high-K diet. Knockout animals treated with exogenous aldosterone also had reduced subunit processing and diminished surface expression of betaENaC and gammaENaC. Expression of the three upstream Na transporters NHE3, NKCC2, and NCC was reduced in both wild-type and knockout mice in response to K loading. The activity of ENaC measured as whole cell amiloride-sensitive current (INa) in principal cells of the cortical collecting duct (CCD) was minimal under control conditions but was increased by a high-K diet to a similar extent in knockout and wild-type animals. INa in the connecting tubule also increased similarly in the two genotypes in response to exogenous aldosterone administration. The activities of both ROMK channels in principal cells and BK channels in intercalated cells of the CCD were unaffected by the deletion of SGK1. Acute treatment of animals with amiloride produced similar increases in Na excretion and decreases in K excretion in the two genotypes. The absence of changes in ENaC activity suggests compensation for decreased surface expression. Altered K balance in animals lacking SGK1 may reflect defects in ENaC-independent K excretion. PMID- 27413202 TI - Nanotechnology: a future tool to improve quality and safety in meat industry. AB - Nanotechnology refers to the new aspect of science modifies its physical, chemical and biological properties leading to new applications or enhanced utility. Keeping the pace with other industries, the meat industry has adopted the new technology in a range of applications to improve the quality and safety of products. The potential applications include the improvement in the tastes, texture, flavor, production of low fat and salt products, enhanced nutrient absorption, improved packaging techniques and better pathogen detection system. However some safety issues need to be addressed before taking a ride on the technology at the full throttle. PMID- 27413201 TI - Apple phenolics as nutraceuticals: assessment, analysis and application. AB - Humankind is presently engulfed by convenience quench, modern life style and urbanized diet system leading to progression in array of health disorders. The past decade confronted cardiometabolic disorder (21.8 %), lower respiratory and chronic obstructive lung disease (12.5 %) as the major causes of death world over. In anticipation, scientific communities' have demonstrated the role of healthy diets, especially those rich in fruits and vegetables, for management of such health related issues. These horticultural crops are considered as a good source of polyphenols such as dihydrochalcones, flavanols, flavonols, anthocyanins and phenolic acids. The present article reviews the efforts made to assess the potential of apple phenolic compounds present in fresh fruits, leaves, bark and pomace as dietary polyphenols. Considering the positive impact of such phytochemicals on human health, various nutraceuticals, dietary supplements and phenolic-rich food products are presently available on market shelves. On analytical front, improved instrumentation based on liquid chromatography (HPLC, UPLC, LC/MS/MS) have made the assessment of phenolics more rapid and reliable. Thus, owing to the emergent interest in natural compounds, it is pertinent to discuss the latest significant research findings on therapeutic aspects along with probable metabolic mechanisms of dietary polyphenols found in apples and their implications on human health. PMID- 27413203 TI - Nutritional and therapeutic perspectives of Chia (Salvia hispanica L.): a review. AB - The ancient grain is becoming enormously popular in modern food regimen in many countries; the higher proportion of alpha-linolenic acid makes chia the superb source of omega-3 fatty (about 65 % of the oil content). Omega-3 fatty acid has been associated with a large number of physiological functions in human body. Chia seed is a potential source of antioxidants with the presence of chlorogenic acid, caffeic acid, myricetin, quercetin, and kaempferol which are believed to have cardiac, hepatic protective effects, anti-ageing and anti-carcinogenic characteristics. It is also a great source of dietary fibre which is beneficial for the digestive system and controlling diabetes mellitus with higher concentration of beneficial unsaturated fatty acids, gluten free protein, vitamin, minerals and phenolic compounds. Therapeutic effects of chia in the control of diabetes, dyslipidaemia, hypertension, as anti-inflammatory, antioxidant, anti-blood clotting, laxative, antidepressant, antianxiety, analgesic, vision and immune improver is scientifically established. PMID- 27413204 TI - Biosensor: an emerging safety tool for meat industry. AB - The meat industry associated with the health hazards like deadly pathogens, veterinary drugs, pesticide residues, toxins and heavy metals is in need of a tool to tackle the awful situation and ensure safer product to consumer. The growth in the industry, global trade scenario, stringent laws and consumer awareness has placed an extra onus on the meat industry to meet out the expectations and demands. Biosensors are the latest tool of detection in the fast growing industries including the food industry. Hence an attempt is envisaged here to review the possibility of harnessing biosensors as tool of safety to safe guard the consumer health and address safety issues in reference to the common threats of concern in the meat industry. PMID- 27413205 TI - Development of antioxidant active films containing sodium ascorbate (SA) and ethylene vinyl alcohol (EVOH) to extend the shelf life of peanut. AB - In this study, low-density polyethylene (LDPE) containing oxygen scavenger based on sodium ascorbate (SA) and ethylene vinyl alcohol (EVOH) at 5, 10 and 15 % concentrations were produced through extrusion method. In addition, the effect of size of SA, thickness LDPE (7.5, 15, 30 and 45 MUm), and number of layers (monolayer, two-layers, three-layers and four-layers) were investigated. Oxygen and water vapor permeability, tensile stress, SA migration and antioxidant activity, thermal stability, scan electron microscopy (SEM), and FT-IR of the films were measured. Moreover, the performance of produced films to prevent of oxidation of packaged peanuts during storage at 40 degrees C was studied. The results revealed that the active films containing SA (especially at 10 % SA) present suitable performance and features to increase the shelf-life of peanuts. PMID- 27413206 TI - Effect of maleylation on physicochemical and functional properties of rapeseed protein isolate. AB - Influence of maleylation on the physicochemical and functional properties of rapeseed protein isolate was studied. Acylation increased whiteness value and dissociation of proteins, but reduced free sulfhydryl and disulfide content (p < 0.05). Intrinsic fluorescence emission and FTIR spectra revealed distinct perturbations in maleylated proteins' tertiary and secondary conformations. Increase in surface hydrophobicity, foaming capacity, emulsion stability, protein surface load at oil-water interface and decrease in surface tension at air-water interface, occurred till moderate level of modification. While maleylation impaired foam stability, protein solubility and emulsion capacity were markedly ameliorated (p < 0.05), which are concomitant with decreased droplet size distribution (d 32). In-vitro digestibility and cytotoxicity tests suggested no severe ill-effects of modified proteins, especially up to low degrees of maleylation. The study shows good potential for maleylated rapeseed proteins as functional food ingredient. PMID- 27413207 TI - Microbiological stability and quality of pulsed light treated cantaloupe (Cucumis melo L. reticulatus cv. Glamour) based on cut type and light fluence. AB - The aim of this study was to investigate the effect of cut type and pulsed light (PL) fluence on microbiological stability and quality of fresh-cut cantaloupes. Fresh-cut cantaloupes with various cut types (cuboid, triangular prism and sphere) were treated with PL technology at 6 J/cm(2). Samples were exposed to PL treatment at fluences of 2.7, 7.8, 11.7 and 15.6 J/cm(2) followed by storage at 4 +/- 1 degrees C for 28 days. Microbiological quality, headspace composition, firmness, colour, pH, titratable acidity, total soluble solids, total phenolic content and ascorbic acid content of fresh-cut cantaloupes were determined. Spherical shape was found to be the most suitable shape for PL treatment of fresh cut cantaloupes due to its significantly lowest (p <= 0.05) microbial counts before and after the PL treatment. No significant (p > 0.05) effect was observed for firmness, colour, total soluble solids and total phenolic content of fresh cut cantaloupes throughout the storage study. Pulsed light treatment using 7.8 J/cm(2) was the best for extending shelf life of fresh-cut cantaloupes with extension of 8 days longer at 4 +/- 1 degrees C compared to the control while maintaining the ascorbic acid content. In conclusion, PL treatment is a potential technique for extending the shelf life of fresh-cut cantaloupes by inactivating microorganisms without compromising the nutritional value. PMID- 27413208 TI - Effect of drying conditions on properties, pigments and antioxidant activity retentions of pretreated orange and purple-fleshed sweet potato flours. AB - Pigmented sweet potatoes (SPs) are outstanding sources of anthocyanin, beta carotene and other color-related phytonutrients. However, fresh SP roots are highly perishable and difficult to store. To reduce losses and extend their uses, fresh SP could be converted into flour. SP cultivars with deep purple (Phichit 65 3) and orange-fleshed (T101) colors newly developed in Thailand were studied. The influence of drying methods on physico-chemical properties, anthocyanin, beta carotene and antioxidant activity retentions of purple and orange-fleshed SP flours (SPFs) was investigated. Peeled purple and orange SPs were pretreated by blanching (100 degrees C, 5 sec) and soaking in 0.5 % (w/v) sodium metabisulphite, then dried in either hot air oven at 50-80 degrees C or steamed for 10 min and placed to the drum dryer at 80-110 degrees C and 3-7 rpm drum speed. The drying processes significantly enhanced anthocyanin contents of SPFs by 1.8 to 3.8 times; however, there was a significant loss of beta-carotene occurred during drying processes. Drum drying yielded SPFs with better color, higher total phenolic contents and antioxidant activity than the hot air drying. Pasting temperatures of hot air dried orange-fleshed SPFs (84-85 degrees C) were slightly higher than those of purple-fleshed SPFs (80-83 degrees C). Drum drying process produced pre-gelatinized (instant) SPFs as indicated by RVA and DSC results. The optimal conditions for drum dried and hot air dried SPF manufactured were 95 degrees C at 5 rpm and 70 degrees C, respectively, based on anthocyanin, beta-carotene, total phenolic, antioxidant activity, color retentions, and pasting properties. PMID- 27413209 TI - Antioxidant activity of various extracts of selected gourd vegetables. AB - Study was conducted to evaluate the antioxidative activity of methanolic (ME), ethanolic (EE) and butanolic extracts (BE) of selected gourd vegetables. The antioxidant activity was investigated using different assays namely ferric thiocyanate test (FTC), thiobarbituric acid test (TBA), ferric reducing antioxidant power (FRAP) and DPPH free radicals scavenging test. A densitometric HPTLC analysis was performed for the analysis of phenolic acids and flavonoids. Different extracts of the selected gourd vegetables revealed different antioxidant activity. Different extracts of Lagenaria siceraria, Momordica charantia and Luffa cylindrica revealed significantly higher (p < 0.05) concentrations of total phenols, flavonids, tannins and carotenoids content and also the antioxidant activity in comparison to remaining vegetable extracts. Correlation studies indicated that FRAP test best described the antioxidant activity of phenols, flavonoids and carotenoids (r = 0.854, 0.692 and 0.915 respectively). HPTLC profiles revealed the presence of maximum number of phenolic acids and flavonoids in L. siceraria and M. charantia. PMID- 27413211 TI - Preparation and evaluation of water-in-soybean oil-in-water emulsions by repeated premix membrane emulsification method using cellulose acetate membrane. AB - The purpose of this study was to investigate the preparation of formulated water- in-soybean oil-in-water emulsions by repeated premix membrane emulsification method using a cellulose acetate membrane. The effect of selective membrane emulsification process parameters (concentration of the emulsifiers, number of passes of the emulsions through the membrane and storage temperature) on the properties and stability of the developed emulsions were also investigated. 1, 3, 6, 8-pyrenetetrasulfonic acid tetrasodium salt (PTSA) was used as a hydrophilic model ingredient for the encapsulation of bioactive substances. W/O emulsions with 7 wt% (weight percentage) PGPR displays homogeneous and very fine dispersions, with the median diameter at 0.640 MUm. Meanwhile, emulsions prepared by membrane emulsification (fine W/O/W) showed the highest stability at Tween 80 concentrations of 0.5 wt.% (weight percentage). It concluded that at 7 wt.% (weight percentage) PGPR concentration and 0.5 wt.% (weight percentage) Tween 80 concentrations, the most uniform particles with minimum mean size of oil drops (9.926 MUm) were obtained after four passes through the membrane. Thus, cellulose acetate membrane can be used for preparing a stable W/O/W emulsions by repeated premix ME due to low cost and relatively easy to handle. PMID- 27413210 TI - Optimization of food materials for development of nutritious pasta utilizing groundnut meal and beetroot. AB - Present study was undertaken to optimize the level of food materials viz. groundnut meal, beetroot juice and refined wheat flour for development of nutritious pasta using response surface methodology. Box-benken design of experiments was used to design different experimental combinations considering 10 to 20 g groundnut meal, 6 to 18 mL beetroot juice and 80 to 90 g refined wheat flour. Quality attributes such as protein content, antioxidant activity, colour, cooking quality (solid loss, rehydration ratio and cooking time) and sensory acceptability of pasta samples were the dependent variables for the study. The results revealed that pasta samples with higher levels of groundnut meal and beetroot juice were high in antioxidant activity and overall sensory acceptability. The samples with higher content of groundnut meal indicated higher protein contents in them. On the other hand, the samples with higher beetroot juice content were high in rehydration ratio and lesser cooking time along with low solid loss in cooking water. The different level of studied food materials significantly affected the colour quality of pasta samples. Optimized combination for development of nutritious pasta consisted of 20 g groundnut meal, 18 mL beetroot juice and 83.49 g refined wheat flour with overall desirability as 0.905. This pasta sample required 5.5 min to cook and showed 1.37 % solid loss and rehydration ratio as 6.28. Pasta sample prepared following optimized formulation provided 19.56 % protein content, 23.95 % antioxidant activity and 125.89 mg/100 g total phenols with overall sensory acceptability scores 8.71. PMID- 27413212 TI - Geometrical, functional, thermal, and structural properties of oat varieties from temperate region of India. AB - Geometrical, functional, thermal properties and FTIR analysis of three varieties of oat flour (Sabzaar, SKO20, & SKO90) were investigated. Sabzaar showed highest thickness, geometric mean diameter, arthimetic mean diameter, sphericity and grain volume. The density of oat grains varied from 0.393 to 0.37 g/mL (bulk) and 1.2 to 1.8 g/mL (true). WAC showed significant (P < 0.05) difference among the cultivars with Sabzaar flour showing the highest value (2.36 g/g) and SKO20 (1.98 g/g) the lowest. Peak viscosity of oat flours was in the range of 460.33-489.33 cP. Flour samples showed the presence of small as well as large starch granules, oval or irregular shape with a smooth surface having some dents or fissures and some damaged starch and with varying dimensions. Average granule size of oat starch samples was within the range of 1.5-6.6 MUm in Sabzaar, 1.1-5.2 MUm in SKO20, and 1.7-6.8 MUm in SKO90. The gelatinization transition temperatures onset temperature (To), peak temperature (Tp), and conclusion temperature (Tc) varied significantly (p < 0.05) among three varieties. PMID- 27413213 TI - Defatted flaxseed meal incorporated corn-rice flour blend based extruded product by response surface methodology. AB - Considering the evidence of flaxseed and its defatted flaxseed meal (DFM) for human health benefits, response surface methodology (RSM) based on three level four factor central composite rotatable design (CCRD) was employed for the development of DFM incorporated corn - rice flour blend based extruded snack. The effect of DFM fortification (7.5-20 %), moisture content of feed (14-20 %, wb), extruder barrel temperature (115-135 degrees C) and screw speed (300-330 RPM) on expansion ratio (ER), breaking strength (BS), overall acceptability (OAA) score and water solubility index (WSI) of extrudates were investigated using central composite rotatable design (CCRD). Significant regression models explained the effect of considered variables on all responses. DFM incorporation level was found to be most significant independent variable affecting on extrudates characteristics followed by extruder barrel temperature and then screw rpm. Feed moisture content did not affect extrudates characteristics. As DFM level increased (7.5 % to 20 %), ER and OAA value decreased. However, BS and WSI values were found to increase with increase in DFM level. Based on the defined criteria for numerical optimization, the combination for the production of DFM incorporated extruded snack with desired sensory attributes was achieved by incorporating 10 % DFM (replacing rice flour in flour blend) and by keeping 20 % moisture content, 312 screw rpm and 125 degrees C barrel temperature. PMID- 27413214 TI - Influence of extraction parameters on physico-chemical characters and antioxidant activity of water soluble polysaccharides from Macrocybe gigantea (Massee) Pegler & Lodge. AB - Polysaccharides from mushrooms are potentially active pharmaceutical ingredients and their action is dependent upon conformation, composition, size etc. In this context, three water soluble crude polysaccharide rich fractions viz. hot water extracted polysaccharide (HWP), cold alkaline extracted polysaccharide (CAP) and hot alkaline extracted polysaccharide (HAP) have been isolated using varying extraction parameters from Macrocybe gigantea, a well-known edible mushroom collected from Gangetic plain of West Bengal and authenticated by DNA barcoding of nrDNA ITS region. Physico-chemical investigation revealed that the fractions were mainly composed of beta-configuration in pyranose form of sugars conjugated with small amount of protein. Further analysis presented that polysaccharides were composed of same monosaccharide even in similar order of ratio (D-glucose > D-galactose > D-mannose > D-xylose). However, D-glucose as well as beta-glucan were found to be in the highest amount in CAP. The helical structure was determined by Congo red assay which indicated that polysaccharides were in aggregate forms except HWP which consisted of tertiary structure. These diverse structural features may have imparted effect on free radical scavenging activity of polysaccharides where HWP was the most active in all assays. HWP was proved to be a good scavenger of free radicals, strong chelator of ferrous ion and had high reducing power. Thus it can be inferred that HWP may foster further studies for searching active compound which might be used as ingredients of functional foods, nutraceuticals and pharmaceuticals. Moreover, to the best of our knowledge this is the first report on chemical composition and antioxidant activity of different crude polysaccharides from M. gigantea. PMID- 27413215 TI - Comparative evaluation of gum arabic coating and vacuum packaging on chilled storage characteristics of Indian mackerel (Rastrelliger kanagurta). AB - The effect of edible coating using gum arabic on biochemical, microbiological, textural and sensory characteristics of fresh gutted mackerel stored at 4 degrees C was investigated. The results were further compared against the samples packed under vacuum (VP) and conventional polyethylene pouches (CP). Coating with gum arabic (GC) markedly retarded lipid oxidation process in gutted mackerel compared to VP and CP samples. Moreover, VP and CP samples showed higher degree of textural deterioration compared to GC samples. Microbiologically, the shelf life of chilled gutted Indian mackerel was estimated to be 7-8, 17 and 19-20 days for CP, GC and VP samples, respectively. The sensory analysis scores confirmed the efficacy of gum coating in retarding the spoilage process during chilled storage. The current study identifies the potential of edible coating with gum arabic to improve the overall quality of Indian mackerel and extend its storage life during chilled storage. PMID- 27413216 TI - Development and quality characteristics of nutritionally enhanced potato legume based wari- an Indian traditional savoury. AB - The present study was carried out to develop waris from potato and legume blends and to analyze them for organoleptic, physicochemical, phytochemical and shelf life quality. Wari is a partially fermented legume based savoury, used as adjunct in vegetable curries. In this study, potato (boiled and dehydrated) was used to supplement black gram or urad dhal waris. Two processing cultivars (Kufri Chipsona-1, Kufri Chandramukhi) and one commonly grown cultivar (Kufri Pukhraj) were evaluated for processing into waris. Based on preliminary sensory trails, waris with potato (70 %) and urad dhal (30 %) level of supplementation were found to be most acceptable and these waris were subjected to nutritional evaluation. Storage stability of the waris was assessed by storing the product at room temperature for a period of 12 months. Results were compared with dhal waris (control). Protein content was significantly higher in control waris compared to potato supplemented waris. Bioactive compounds including ascorbic acid, total phenolics and total antioxidant activity measured as DPPH radical scavenging activity increased significantly on incorporation of potato. Between the cultivars, waris enriched with Kufri Pukhraj, a table variety which is considered unfit for processing, displayed the highest phytochemical content and total antioxidant activity. Sensory evaluation indicated higher overall acceptability scores of potato enriched waris compared to control waris. Between the treatments i.e. boiled mash and dehydrated flour, waris supplemented with boiled potato mash showed a significantly higher content of phytochemicals and total antioxidant activity compared to potato flour waris. However no significant difference was observed in sensory quality of the product prepared either with fresh potato mash or potato flour. Storage studies showed that the potato waris can be stored safely for 12 months with its nutrient constituents intact. PMID- 27413217 TI - Antioxidant and cyto/DNA protective properties of apple pomace enriched bakery products. AB - Apple pomace (AP), the residue that remains after the extraction of juice from apple accounts for ~25 % of total apple weight. Current study is aimed at identification of phytochemicals and utilization of Dehydrated apple pomace (DAP) in the preparation of bakery products with potential health benefits. DAP was prepared by drying the pomace obtained by crushing peeled apple fruits. DAP was incorporated into bakery products such as bun, muffin and cookies for value addition. Bioactivity such as free radical scavenging, cyto/DNA protectivity was evaluated in these products. DAP contained 17 g/100 g starch, 49.86 g/100 g fructose and 37 g/100 g dietary fibre. The phenolics and flavonoids content was 1.5 mg/g and 3.92 mg/g, respectively. Increase in DAP resulted in decreased volume and enhanced firmness of buns and muffins. DAP at 15 % in buns, 30 % in muffins and 20 % in cookies were found to be acceptable. DAP blended products exhibited better free radical scavenging as well as cyto/DNA protective properties suggesting the retention of bioactivity after baking. Addition of DAP potentially enhanced the bioactivity of the products evaluated. PMID- 27413218 TI - Multivariate optimization of a synergistic blend of oleoresin sage (Salvia officinalis L.) and ascorbyl palmitate to stabilize sunflower oil. AB - The simultaneous optimization of a synergistic blend of oleoresin sage (SAG) and ascorbyl palmitate (AP) in sunflower oil (SO) was performed using central composite and rotatable design coupled with principal component analysis (PCA) and response surface methodology (RSM). The physicochemical parameters viz., peroxide value, anisidine value, free fatty acids, induction period, total polar matter, antioxidant capacity and conjugated diene value were considered as response variables. PCA reduced the original set of correlated responses to few uncorrelated principal components (PC). The PC1 (eigen value, 5.78; data variance explained, 82.53 %) was selected for optimization using RSM. The quadratic model adequately described the data (R (2) = 0. 91, p < 0.05) and lack of fit was insignificant (p > 0.05). The contour plot of PC 1 score indicated the optimal synergistic combination of 1289.19 and 218.06 ppm for SAG and AP, respectively. This combination of SAG and AP resulted in shelf life of 320 days at 25 degrees C estimated using linear shelf life prediction model. In conclusion, the versatility of PCA-RSM approach has resulted in an easy interpretation in multiple response optimizations. This approach can be considered as a useful guide to develop new oil blends stabilized with food additives from natural sources. PMID- 27413219 TI - Malting process optimization for protein digestibility enhancement in finger millet grain. AB - Finger millet (Eleusine coracana) is a nutritious, gluten-free, and drought resistant cereal containing high amounts of protein, carbohydrate, and minerals. However, bio-availability of these nutrients is restricted due to the presence of an excessive level of anti-nutrient components, mainly phytic acid, tannin, and oxalate. It has been shown that a well-designed malting/germination process can significantly reduce these anti-nutrients and consequently enhance the nutrient availability. In the present study, the effects of two important germination factors, duration and temperature, on the enhancement of in-vitro protein digestibility of finger millet were thoroughly investigated and optimized. Based on a central composite design, the grains were germinated for 24, 36, and 48 h at 22, 26, and 30 degrees C. For all factor combinations, protein, peptide, phytic acid, tannin, and oxalate contents were evaluated and digestibility was assessed. It was shown that during the malting/germinating process, both temperature and duration factors significantly influenced the investigated quantities. Germination of finger millet for 48 h at 30 degrees C increased protein digestibility from 74 % (for native grain) up to 91 %. Besides, it notably decreased phytic acid, tannin, and oxalate contents by 45 %, 46 %, and 29 %, respectively. Linear correlations between protein digestibility and these anti nutrients were observed. PMID- 27413220 TI - Cross-flow deep fat frying and its effect on fry quality distribution and mobility. AB - Conventional industrial frying systems are not optimised towards homogeneous product quality, which is partly related to poor oil distribution across the packed bed of fries. In this study we investigate an alternative frying system with an oil cross-flow from bottom to top through a packed bed of fries. Fluidization of rectangular fries during frying was characterised with a modified Ergun equation. Mixing was visualized by using two coloured layers of fries and quantified in terms of mixing entropy. Smaller fries mixed quickly during frying, while longer fries exhibited much less mixing, which was attributed to the higher minimum fluidization velocity and slower dehydration for longer fries. The cross flow velocity was found an important parameter for the homogeneity of the moisture content of fries. Increased oil velocities positively affected moisture distribution due to a higher oil refresh rate. However, inducing fluidization caused the moisture distribution to become unpredictable due to bed instabilities. PMID- 27413221 TI - Effect of nano-alumina concentration on the mechanical, rheological, barrier and morphological properties of guar gum. AB - In this work, nano-alumina was utilized as a reinforcing agent for guar gum, with an aim to improve its performance properties; especially, mechanical and barrier i.e. water vapor transmission rate (WVTR). Films were prepared by the process of solution casting. Concentration of nano-alumina was varied as 0, 1, 3, 5 and 7 parts per hundred parts of resin (phr) in guar gum. The prepared pristine and guar gum/alumina nano-composite films were characterized for mechanical, puncture, x-ray diffraction, barrier, rheological and morphological properties. Tensile strength, Young's modulus, puncture strength, viscosity and crystallinity increased; whereas, WVTR, elongation at break (%) and damping factor decreased with increased concentration of nano-alumina in guar gum. However, optimized improvement in the performance properties were determined for 5 phr nano-alumina loaded guar gum polymer matrix, attributed to its better dispersion and interaction into the guar gum polymer chains due to the hydrophilic nature of both the materials. Above 5 phr concentration nano-alumina started forming aggregates, as evident from scanning electron microscopy. PMID- 27413222 TI - Characterization of aroma-active and phenolic profiles of wild thyme (Thymus serpyllum) by GC-MS-Olfactometry and LC-ESI-MS/MS. AB - The present study was designed to characterize the volatile, aroma-active and phenolic compounds of wild thyme. Volatile components of T. serpyllum were extracted by use of the purge and trap technique with dichloromethane and analyzed by gas chromatography-mass spectrometry (GC-MS). The extraction method gave highly representative aromatic extract of the studied sample based on the sensory analysis. A total of 24 compounds were identified and quantified in Thymus serpyllum. Terpenes were qualitatively and quantitatively the most dominant volatiles in the sample. Aroma extract dilution analysis (AEDA) was used for the first time for the determination of aroma-active compounds of Thymus serpyllum. In total, 12 aroma-active compounds were detected in the aromatic extract by GC-MS-Olfactometry and terpenes were the most abundant compounds. High performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was used for the phenolic compounds analysis. 18 phenolic compounds were identified and quantified in the T. serpyllum. Luteolin 7-O-glucoside, luteolin and rosmarinic acid were the most abundant phenolics in this herb. PMID- 27413223 TI - Postharvest shelf-life extension of pink guavas (Psidium guajava L.) using HPMC based edible surface coatings. AB - Psidium guajava L. var. 'Lalit' is a perishable fruit with delicate skin which is prone to damage. The objective of this study was to determine the effect of edible coating made up of hydroxypropyl methyl cellulose and palm oil on ripening of guava. Coating solution was applied over fruits and coated fruits were stored at 24 +/- 1 degrees C and 65 +/- 5%RH. Changes in fruit colour, texture softening, respiration rate, weight loss, ascorbic acid content, soluble solids, titrable acidity, chlorophyll content, total reducing sugars, total phenolic content were studied during post-harvest ripening. Fruits coated with 1 % of hydroxypropyl methyl cellulose and 0.3 % of palm oil showed significant delay in weight loss, fruit firmness as well as colour change (p < 0.05). Coating delayed the enzyme activities of peroxidase and polyphenol oxidase of the fruit. Results suggest that overall quality of coated fruit was maintained by edible coating formulation extending the shelf life of fruit up to 12 days with appreciable retention of all quality parameters tested. PMID- 27413224 TI - Application of edible coating with starch and carvacrol in minimally processed pumpkin. AB - The present study evaluated the effect of an edible coating of cassava starch and carvacrol in minimally processed pumpkin (MPP). The minimal inhibitory concentration (MIC) of carvacrol against Escherichia coli, Salmonella enterica serotype Typhimurium, Aeromonas hydrophila, and Staphylococcus aureus was determined. The edible coating that contained carvacrol at the MIC and 2 * MIC was applied to MPP, and effects were evaluated with regard to the survival of experimentally inoculated bacteria and autochthonous microflora in MPP. Total titratable acidity, pH, weight loss, and soluble solids over 7 days of storage under refrigeration was also analyzed. MIC of carvacrol was 312 MUg/ml. Carvacrol at the MIC reduced the counts of E. coli and S. Typhimurium by approximately 5 log CFU/g. A. hydrophila was reduced by approximately 8 log CFU/g, and S. aureus was reduced by approximately 2 log CFU/g on the seventh day of storage. Carvacrol at the 2 * MIC completely inhibited all isolates on the first day of Storage. coliforms at 35 degrees C and 45 degrees C were not detected (< 3 MPN/g) with either treatment on all days of shelf life. The treatment groups exhibited a reduction of approximately 2 log CFU/g in psychrotrophic counts compared with controls on the last day of storage. Yeast and mold were not detected with either treatment over the same period. The addition of carvacrol did not affect total titratable acidity, pH, or soluble solids and improved weight loss. The edible coating of cassava starch with carvacrol may be an interesting approach to improve the safety and microbiological quality of MPP. PMID- 27413225 TI - Preparation, characterization and in vitro antioxidative potential of synbiotic fermented dairy products. AB - The present study, evaluates the antioxidative potential of two synbiotic dairy products viz. synbiotic lassi with honey and whey based synbiotic drink with inulin and orange juice, along with their physicochemical and microbiological activity during storage period. Antioxidative potential of raw ingredients and probiotic cultures used to prepare synbiotic products was also evaluated. Synbiotic lassi with honey was prepared using Streptococcus thermophilus MTCC 5460 (MD2) and Lactobacillus helveticus MTCC 5463 (V3) as probiotics and honey as prebiotic. For preparation of whey based synbiotic drink, Lactobacillus helveticus MTCC 5463 and inulin were used as probiotic and prebiotic, respectively and orange juice was also incorporated. Titratable acidity and pH of both synbiotic products followed a similar pattern of increase or decrease during storage. Furthermore, no major changes were observed in viability of probiotic cultures under storage conditions adapted. The hydroxyl radical scavenging activity of synbiotic lassi with honey was found to significantly decrease from 107.76 to 79.41 % at the end of storage whereas, the activity of whey based synbiotic drink was 100.32 % which declined sharply to 79.21 % on 7th day but further increased to 102.59 % on 14th day. The DPPH (alpha, alpha-Diphenyl-beta Picrylhydrazyl) radical scavenging activity of freshly prepared synbiotic lassi with honey was 28.43 % which decreased to 23.03 % on 7th day while for whey based synbiotic drink decreased from 26.85 % (0 day) to 17.12 % (7th day) and continued to decline. Moreover, probiotic strains used for synbiotic preparation also demonstrated good antioxidative activity. PMID- 27413226 TI - Antioxidant components and properties of dry heat treated clove in different extraction solvents. AB - The effects of heat treatment and extraction solvents (pure/aqueous acetone, ethanol, methanol) on antioxidant activity (AA) and components of clove (Syzygium aromaticum Linn) were studied. Clove was subjected to dry heat treatment (microwave and roasting) and the AA measured by free radical scavenging activity (FRSA), reducing power (RP), and phospho-molybdenum assay (TAA). Unheated samples served as controls. The antioxidant components estimated were total phenols, flavonoids and tannins. Using RP and FRSA, highest AA was observed in 80 % acetone extract of all samples (1.778-1448 and 84.5-86.0 %). TAA showed higher value in 80 % methanolic extract for all samples in the range 303.595-307.941 mmol ascorbic acid/g. Heated samples exhibited higher AA in all assays. Highest amount of phenols and flavonoids were extracted in 80 % acetone (4053-4064 mg/100 g) and 80 % methanol (11,271-11,370 mg/100 g) respectively. For tannins, maximum extraction was in 80 % acetone (control, 16441 mg/100 g), 80 % ethanol (microwave, 19,558 mg/100 g), and pure methanol (roasted, 15,823 mg/100 g). Total phenol and flavonoid contents were positively associated with AA determined using RP and FRSA. In conclusion, clove exhibited powerful AA in different extraction solvents which increased on dry heat treatments and correlated positively with antioxidant components. Hence, clove can be used as a natural antioxidant in food systems. PMID- 27413227 TI - Relationship of dietary factors with dialyzable iron and in vitro iron bioavailability in the meals of farm women. AB - Sixty rural women with age varying between 25 and 35 were selected randomly to determine the role of dietary factors on bioavailability of iron in their diets. Food samples of selected subjects were collected for three major meals i.e. breakfast, lunch and dinner for three consecutive days. The samples were analyzed for meal constituents associated with iron absorption as well as for total and dialyzable iron. Based on dietary characteristics, the diets of the farm women were in the class of intermediate diets as per FAO/WHO classification with iron bioavailability of 8.11 %. The statistical analysis revealed that the meal constituents which were found to influence iron absorption positively were ascorbic acid and beta-carotene in breakfast and only beta-carotene in dinner. The meal constituents which affected iron absorption negatively were zinc and calcium in breakfast as well as lunch and phytates and NDF in dinner, however, polyphenols present in the meals of the subjects did not show any relationship with iron absorption. PMID- 27413228 TI - Studies on the effect of ohmic heating on oil recovery and quality of sesame seeds. AB - This research describes a new technological process for sesame oil extraction. The process deals with the effect of ohmic heating on enhancement of oil recovery and quality of cleaned and graded sesame seed. The effect of ohmic heating parameters namely electric field strength (EFS), end point temperature (EPT) and holding time (HT) on oil extraction process were investigated. Three levels of electric field strength (600, 750 and 900 V/m), end point temperature (65, 75 and 85 degrees C) and holding time (5, 10 and 15 min.) were taken as independent variables using full factorial design. Percentage oil recovered from sesame seed through mechanical extracted oil by application of ohmic heating varies from 39.98 to 43.15 %. The maximum oil recovery 43.15 % was obtained when the sample was heated and maintained at 85 degrees C using EFS of 900 V/m for a holding time of 10 min as against 34.14 % in control sample. The free fatty acid (FFA) of the extracted oil was within the acceptable limit (1.52 to 2.26 % oleic acid) of 0.5 to 3 % as prescribed respectively by Prevention of Food Adulteration (PFA) and Bureau of Indian Standards (BIS). The peroxide value of extracted oil was also found within the acceptable limit (0.78 to 1.01 meq/kg). The optimum value for maximum oil recovery, minimum residual oil content, free fatty acid (FFA) and peroxide value were 41.24 %, 8.61 %, 1.74 % oleic acid and 0.86 meq/kg, respectively at 722.52 V/m EFS at EPT 65 degrees C for 5 min. holding time which was obtained by response surface methodology. PMID- 27413229 TI - Preparation of human milk fat analogue by enzymatic interesterification reaction using palm stearin and fish oil. AB - Palm stearin fractionate (PSF), obtained from palm stearin by further fractionation with solvents and n-3 polyunsaturated fatty acids (n-3 PUFA) rich fish oil (FO) were subjected to interesterification at 1:1, 1:2, 1:3, 2:1 and 3:1 substrate molar ratio and catalyzed by lipase from Thermomyces lanuginosa for obtaining a product with triacylglycerol (TAG) structure similar to that of human milk fat (HMF). The parameters (molar ratio and time) of the interesterification reaction were standardized. The temperature of 60 degrees C and enzyme concentration of 10 % (w/w) were kept fixed as these parameters were previously optimized. The reactions were carried out in a stirred tank reactor equipped with a magnetic stirrer for 6, 12, 18 and 24 h. The blends were analyzed for fatty acid (FA) composition of both total FAs and those at the sn-2 position after pancreatic lipase hydrolysis. All the blended products were subjected to melting point determination and free fatty acid content. Finally, blend of PSF and FO at 2:1 molar ratio with 69.70 % palmitic acid (PA) content and 12 h of reaction produced the desired product with 75.98 % of PA at sn-2 position, 0.27 % arachidonic acid (AA), 3.43 % eicosapentaenoic acid (EPA) and 4.25 % docosahexaenoic acid (DHA) and with melting point of 42 degrees C. This study portrayed a successful preparation of TAG containing unique FA composition i.e. >= 70 % of the PA, by weight, were esterified at the sn-2 position which could be used in infant formulation with health benefits of n-3 PUFAs. PMID- 27413230 TI - Effect of particle size on antioxidant activity and catechin content of green tea powders. AB - This work evaluated the effect of grinding and sieving process of green tea leaves on particle size distribution and antioxidant activity. Granulometric classes ranging from 20 MUm to 500 MUm were studied. Hydroalcoholic extracts of green tea powders (GTPs) were analysed for total phenolic, total flavonoid, and catechin contents. The fraction of 100-180 MUm ground at 6000 rpm showed the maximum catechin content with 33.5 mg/g dry matter (DM) and, the best antioxidant activity with IC50 values of 0.28 MUg/mL and 0.13 MUg/mL using DPPH and ABTS radical scavenging assays, respectively. However, antioxidant properties and catechin content decreased for particle of sizes less than 50 MUm. Catechin content was higher for those ground at 6000 rpm as compared to at 18,000 rpm. The best grinding conditions and particle size were 6000 rpm and 100-180 MUm. PMID- 27413231 TI - Effect of inclusion of key foods on in vitro iron bioaccessibility in composite meals. AB - The in vitro bioaccessibility of iron in context to fortification of key foods to cereal based diets was studied to optimize the meals for enhanced iron bioaccessibility to meet the needs of vegetarian and non-vegetarian adult women. Four individual food items and thirty six composite meals were selected to represent a wide spectrum of meal ingredients. The four individual foods: chapati, rice, dal and saag were choosen on the basis of data reported on meal pattern of surveyed households of north India. The basic meals were then fortified with key food ingredients which may influence in vitro iron bioaccessibility. Eight selected key foods were salad, orange, lemonade, milk, curd, chicken, egg and tea. The results revealed that inclusion of 200 g of chicken, 135 g of salad and 120 g of orange to the basic meals of rice or chapati with either dal or saag enhanced iron bioaccessibility by 1.6 fold to 5.0 fold; 5.2 to 28.9 % and 4.7 to 10.7 %, respectively. The best enhancer of iron absorption for vegetarians was lemonade (250 ml) which resulted in 70.2 and 61.0 % increase of in vitro bioaccessibility of iron to the rice based meals with dal and saag, respectively. The inclusion of lemonade resulted in 1.3 fold increase in iron bioaccessibility in chapati based meals. The major inhibitors of iron bioaccessibility were egg and tea, the percent reduction caused by egg being 16.1 to 50.2 % while by tea, it was between 21.5 to 55.3 %. The study recommends that those vulnerable to iron deficiency should be encouraged to increase overall intake of iron from iron rich foods. The increase should be coupled with efforts to combine appropriate foods in the diet to enhance the bioaccessibility of iron and reduce inhibitory factors. PMID- 27413232 TI - Variation in biochemical parameters in different parts of potato tubers for processing purposes. AB - The present study was conducted to estimate the variation in bio-chemical parameters among eight different parts viz. bud end cortex, bud end medulla, central cortex, central medulla, pith, stem end cortex, stem end medulla and peel of potato tuber of processing varieties. Concentration of dry matter, reducing sugar, sucrose and starch content were higher in cortical region than in medullar region of stem end, bud end and central portion. Variety Kufri Chipsona-1 had maximum dry matter content in stem end cortex (SEC 30.34 %), followed by Kufri Frysona (SEC 27.71 %). Mean reducing sugar values were comparatively more in bud end cortex (BEC 111.3 mg/100 g Fresh Weight) and lowest in stem end medulla (SEM 44.05 mg/100 g FW). Bio-chemical contents varied considerably within different parts of tuber as well as in different genotypes. The information generated in this study can help processors for effective utilization of potato for various types of processing products viz., chips and French fries. PMID- 27413233 TI - Comparative study on conventional, ultrasonication and microwave assisted extraction of gamma-oryzanol from rice bran. AB - In present study, conventional, ultrasonic and microwave assisted extraction methods were compared with the aim of optimizing best fitting solvent and method, solvent concentration and digestion time for high yield of gamma-oryzanol from rice bran. Petroleum ether, hexane and methanol were used to prepare extracts. Extraction yield were evaluated for giving high crude oil yield, total phenolic content (TPC) and gamma-oryzanol content. Gas chromatography-mass spectrophotometry was used for the determination of gamma-oryzanol concentration. The highest concentration of gamma-oryzanol was detected in methanolic extracts of microwave treatment (85.0 ppm) followed by ultrasonication (82.0 ppm) and conventional extraction method (73.5 ppm). Concentration of gamma-oryzanol present in the extracts was found to be directly proportional to the total phenolic content. A combination of 80 % methanolic concentration and 55 minutes digestion time of microwave treatment yielded the best extraction method for TPC and thus gamma-oryzanol (105 ppm). PMID- 27413234 TI - Bifidus milk powder: processing parameter standardization and shelf stability evaluation. AB - Spray dried bifidus milk powder was prepared by supplementing cow milk with different level of additives to obtain slurry of desired concentration. The slurry was pasteurized, cooled and inoculated with Bifidobacterium bifidum, incubated and dried to produce a bifidus milk powder. Among the various bifidus milk powder prepared, the slurry of mention the level total soluble solids exhibited good organoleptic characteristics and it has been standardized for further analysis. Moisture content, bulk density, insolubility index, hydroxymethyl furfural and thiobarbituric acid value of bifidus milk powder significantly increased, while the reflectance value significantly decreased during storage. The B. bifidum count significantly reduced and the bacterium were not detected at the end of the mention storage duration. As such the sentence is not acceptable in the abstract. The reconstituted bifidus milk powder was considered acceptable with an overall acceptability score of 6.97 on a nine-point Hedonic scale and showed a shelf stability of 120 days at ambient temperature condition (27 +/- 2 degrees C). PMID- 27413235 TI - Evaluation of dough rheological properties and bread texture of pearl millet wheat flour mix. AB - This study was undertaken with the objective of formulating composite bread using pearl millet (Pennisetum glaucum) and wheat (Triticum aestivum) flours . Rheological and bread making properties of composite flours were evaluated. Mixolab results revealed torque increased and dough stability time decreased upon incorporation of pearl millet flour in wheat flour. The incorporation of millet flour at optimum level (5 %) led to an increase of the dough strength (W) and the elasticity-to-extensibility ratio (P/L) by 31 % and 65 % respectively. The bread texture and volume were also improved. These findings indicated the potentiality of using millet flour in bread making. PMID- 27413236 TI - Determination of relationship between sensory viscosity rating and instrumental flow behaviour of soluble dietary fibers. AB - The shear-thinning low, medium and high-viscosity fiber preparations (0.15-1.05 % psyllium husk, 0.07-0.6 % guar gum, 0.15-1.20 % gum tragacanth, 0.1-0.8 % gum karaya, 0.15-1.05 % high-viscosity Carboxy Methyl Cellulose and 0.1-0.7 % xanthan gum) showed that the consistency coefficient (k) was a function of concentration, the relationship being exponential (R(2), 0.87-0.96; P < 0.01). The flow behaviour index (n) (except for gum karaya and CMC) was exponentially related to concentration (R(2), 0.61-0.98). The relationship between k and sensory viscosity rating (SVR) was essentially linear in nearly all cases. The SVR could be predicted from the consistency coefficient using the regression equations developed. Also, the relationship of k with fiber concentration would make it possible to identify the concentration of a particular gum required to have desired consistency in terms of SVR. PMID- 27413237 TI - Species identification of cattle and buffalo fat through PCR assay. AB - A method was standardized to isolate quality DNA from cattle and buffalo fat for species identification using QIAamp DNA stool mini kit. The quality of the DNA was sufficient enough to amplify universal primers viz., mt 12S rRNA and mt 16S rRNA, and species specific D loop primers for cattle and buffalo. The sensitivity of the PCR assay in the species specific D loop primer amplification was with a detection level of 0. 47 ng cattle DNA and 0.23 ng buffalo DNA in simplex and, 0. 47 ng cattle DNA and 0.12 ng buffalo DNA in duplex PCR. It is a potentially reliable method for DNA detection to authenticate animal fat. PMID- 27413238 TI - Effect of protein concentrations on the properties of fish myofibrillar protein based film compared with PVC film. AB - The effect of protein concentrations on the properties of fish myofibrillar protein film (FMP) were investigated and compared with commercial wrap film (polyvinyl chloride; PVC). FMP (2 %, w/v) showed the highest mechanical properties [tensile strength: 4.38 MPa and elongation at break: 133.05 %], and water vapor permeability [2.81 * 10(-10) g m(-1) s(-1) Pa(-1)]. FMP contained high molecular weight cross-links, resulting in complex film network, as indicated by lower film solubility (19-22 %) and protein solubility (0.6-1.3 %). FMP showed excellent barrier properties to UV light at the wavelength of 200-280 nm. FMP had the thickness [0.007-0.032 mm], color attributes and transparency similar to PVC film [thickness: 0.010 mm]. Therefore, protein concentration majority influenced the properties of develop FMP. The protein content of 1 % (w/v) had potential to be developed the biodegradable film with comparable properties to the commercial wrap film. PMID- 27413239 TI - Characterisation of viscosity, colour, 5-hydroxymethylfurfural content and diastase activity in raw rape honey (Brassica napus) at different temperatures. AB - The effect of heating at various temperatures (30, 40, 50, 60, 70 and 80 degrees C) on dynamic viscosity, colour, 5-hydroxymethylfurfural (5-HMF) concentration and diastase activity of raw rape honey were assessed. In fresh honey, moisture, ash, free acidity, pH and electrical conductivity averaged 185.3 g kg(-1), 1.2 g kg(-1), 18.71 mEq kg(-1), 4.2 and 0.25 mS cm(-1), respectively. Heating significantly (p <= 0.05) increased lightness (L*), yellowness (b*), chroma (C*), hue (h degrees ) values, but decreased redness (a*). The viscosity at 20 degrees C (33.6 Pa s) differed significantly (p <= 0.01) with those at 30, 40 and 50 degrees C (8.2, 2.5, and 1.6 Pa s, respectively). Diastase activity decreased concomitant with heating at higher temperatures. Honey heated at 80 degrees C for 15 min showed the maximum increase of 5-HMF content, with an average of 1.9 mg kg(-1) (62 %), compared to unheated samples. Heating for 15 min between 50 degrees C and 80 degrees C did not significantly degrade the quality of the honey, but, slightly enhanced formation of 5-HMF and reduced the diastase activity. PMID- 27413240 TI - Effect of chitosan on shelf life of restructured fish products from pangasius (pangasianodon hypophthalmus) surimi during chilled storage. AB - In the present study, restructured products were prepared from pangasius surimi and their qualities were analysed under chilled storage. Pangasius surimi had 75.82 % moisture, 16.91 % protein, 2.76 % fat and 0.95 % ash. Restructured products were prepared in three different formulations by incorporating corn starch (10 %) and chitosan (0.75 %). Formulation containing only corn starch (10 %) was served as control. In all the formulations, mono unsaturated fatty acids were higher (45.14 %). The total volatile base nitrogen (TVB-N) showed an increasing trend and it was found to be higher in control (4.8 mg/100 g) on 10(th) day than the chitosan incorporated sample (3.5-4.2 mg/100 g) on 17(th) day during chill storage. Similarly, peroxide value (PV) was found to higher (8.85 milliequivalent of O2/kg) in control than the chitosan incorporated sample (4.5 6.8 milliequivalent of O2/kg) on 10(th) day. All the three formulations had an acceptable level of thiobarbituric acid (TBA) value that ranged between 0.023 0.098 mg of malanoldehyde/kg during chilled storage. Based on the sensory and microbiological analysis, products prepared without chitosan had a shelf life of 10 day whereas, products incorporated with chitosan had an extended shelf life of 17 day. PMID- 27413241 TI - Efficient and eco-friendly extraction of corn germ oil using aqueous ethanol solution assisted by steam explosion. AB - An improved aqueous extraction method has been established for extraction of oil from corn germs. This method primarily included steam explosion pretreatment and aqueous ethanol extraction. Process variables such as steam pressure, resident time, particle size and ethanol concentration were investigated. The highest yield of 93.74 % was obtained when ground steam-exploded corn germ (1.3 MPa, 30 s, 30-35 MUm particle size) was treated with 30 % (v/v) aqueous ethanol for 2 h, at 60 degrees C and pH 9.0. The residual oil content in water and sediment phase decreased dramatically to 4 % and 3 %, respectively. The enhancement mechanism of the process induced by steam explosion was analyzed by confocal laser scanning microscope (CLSM). The quality of extracted crude oil was also investigated. The results showed that the quality of extracted oil was superior to commercial oils. PMID- 27413242 TI - Impact of low-trans fat compositions on the quality of conventional and fat reduced puff pastry. AB - Four vegetable fat blends (FBs) with low trans-fatty acid (TFA <= 0.6 %) content with various ratios of palm stearin (PS) and rapeseed oil (RO) were characterised and examined for their application in puff pastry production. The amount of PS decreased from FB1 to FB4 and simultaneously the RO content increased. A range of analytical methods were used to characterise the FBs, including solid fat content (SFC), differential scanning calorimetry (DSC), cone penetrometry and rheological measurements. The internal and external structural quality parameters of baked puff pastry were investigated using texture analyser equipped with an Extended Craft Knife (ECK), VolScan and C-Cell image system. Puff pastry containing FB1 and FB2 achieved excellent baking results for full fat and fat-reduced puff pastry; hence these FBs contained adequate shortening properties. A fat reduction by 40 % using FB2 and a reduction of saturated fatty acids (SAFA) by 49 %, compared to the control, did not lead to adverse effects in lift and specific volume. The higher amount of RO and the lower SAFA content compared to FB1 coupled with the satisfying baking results makes FB2 the fat of choice in this study. FB3 and FB4 were found to be unsuitable for puff pastry production because of their melting behaviour. PMID- 27413243 TI - Physicochemical and rheological properties of starch and flour from different durum wheat varieties and their relationships with noodle quality. AB - Starch and flour properties of different Indian durum wheat varieties were evaluated and related to noodle-making properties. Flours were evaluated for pasting properties, protein characteristics (extractable as well as unextractable monomeric and polymeric proteins) and dough rheology (farinographic properties), while starches were evaluated for granule size, thermal, pasting, and rheological properties. Flour peak and final viscosities related negatively to the proportion of monomeric proteins but positively to that of polymeric proteins whereas opposite relations were observed for dough rheological properties (dough development time and stability). Starches from varieties with higher proportion of large granules showed the presence of less stable amylose-lipids and had more swelling power, peak viscosity and breakdown viscosity than those with greater proportion of small granules. Noodle-cooking time related positively to the proportion of monomeric proteins and starch gelatinization temperatures but negatively to that of polymeric proteins and amylose content. Varieties with more proteins resulted in firmer noodles. Noodle-cohesiveness related positively to the proportion of polymeric proteins and amylose-lipids complexes whereas springiness correlated negatively to amylose content and retrogradation tendency of starches. PMID- 27413244 TI - Does squalene alter the antioxidant potential of astaxanthin and fucoxanthinol? In vitro evidence in RAW 264.7 cells, a murine macrophage. AB - Astaxanthin (Ax) and fucoxanthin/fucoxanthinol (FuOH) are marine xanthophylls exhibiting anti-oxidant effects. Squalene (SQ) is a triterpenoid and is a precursor of sterols. This study aimed to determine if SQ can improve the effect of Ax/FuOH on lipid peroxidation. RAW 264.7 cells were treated with different concentrations of Ax, FuOH and SQ and corresponding rate of cell survival was noted. In addition,combination groups - Ax + SQ and FuOH + SQ- were also run. Cells treated with Ax, FuOH, SQ, Ax + SQ and FuOH + SQ were stimulated with lipopolysaccharide and lipid hydroperoxides were estimated. Results showed that 5 MUM Ax, 2 MUM FuOH and 10 MUM SQ supported cell survival. In presence of SQ, cell viability improved for higher concentrations of FuOH (5, 10 MUM). Lipid hydroperoxides were supressed by Ax, FuOH, Ax + SQ and FUOH +SQ and were significantly lower in Ax + SQ, indicating the synergistic effect of Ax and SQ. To conclude, combination of Ax with SQ enhances its ability to supress lipid peroxidation while with FuOH, SQ attenuates the toxic effect at higher doses. Moreover, this is the first time that the combined effect of SQ and carotenoids has been studied and reported. PMID- 27413245 TI - Determination of triacyl glycerol and sterol components of fat to authenticate ghee based sweets. AB - Method comparison of triacyl glycerol (TAG) and sterol components of fats of ghee based sweets was carried out on dairy ghee, laboratory prepared control sample and market samples. The fat was extracted from control and market samples. Determination of TAG and sterol composition of the fats was carried out using low resolution Gas Chromatography. The quantification of cholesterol and beta sitosterol and TAG classes of dairy ghee, control and market samples fat was also determined using single short column. Adulteration at 5 % level in milk fats showed varied TAG compositions of C50, C52 and C54 as compared to control and pure ghee sample. The cholesterol content of ghee and control sample was 2.30 +/- 0.8, 2.00 +/- 0.24 g/kg respectively and beta-sitosterol content of control was 0.20 +/- 0.11 g/kg. The adulterated samples showed varied cholesterol and beta sitosterol contents as compared to control sample fat. PMID- 27413246 TI - Synthesis of 5-Hydroxymethylcytidine- and 5-Hydroxymethyl-uridine-Modified RNA. AB - We report on the syntheses of 5-hydroxymethyl-uridine [5hm(rU)] and -cytidine [5hm(rC)] phosphoramidites and their incorporation into RNA by solid-phase synthesis. Deprotection of the oligonucleotides is accomplished in a straightforward manner using standard conditions, confirming the appropriateness of the acetyl protection used for the pseudobenzylic alcohol moieties. The approach provides robust access to 5hm(rC/U)-modified RNAs that await applications in pull-down experiments to identify potential modification enzymes. They will also serve as synthetic probes for the development of high-throughput sequencing methods in native RNAs. 1Introduction2Protection Strategies Reported for the Synthesis of 5hm(dC)-Modified DNA3Synthesis of 5-Hydroxymethylpyrimidine Modified RNA3.1Synthesis of 5hm(rC) Phosphoramidite3.2Synthesis of 5hm(rU) Phosphoramidite3.3Synthesis of 5hm(rC)- and 5hm(rU)-Modified RNA4Conclusions. PMID- 27413248 TI - Unsupervised fetal cortical surface parcellation. AB - At the core of many neuro-imaging studies, atlas-based brain parcellations are used for example to study normal brain evolution across the lifespan. These atlases rely on the assumption that the same anatomical features are present on all subjects to be studied and that these features are stable enough to allow meaningful comparisons between different brain surfaces and structures These methods, however, often fail when applied to fetal MRI data, due to the lack of consistent anatomical features present across gestation. This paper presents a novel surface-based fetal cortical parcellation framework which attempts to circumvent the lack of consistent anatomical features by proposing a brain parcellation scheme that is based solely on learned geometrical features. A mesh signature incorporating both extrinsic and intrinsic geometrical features is proposed and used in a clustering scheme to define a parcellation of the fetal brain. This parcellation is then learned using a Random Forest (RF) based learning approach and then further refined in an alpha-expansion graph-cut scheme. Based on the votes obtained by the RF inference procedure, a probability map is computed and used as a data term in the graph-cut procedure. The smoothness term is defined by learning a transition matrix based on the dihedral angles of the faces. Qualitative and quantitative results on a cohort of both healthy and high-risk fetuses are presented. Both visual and quantitative assessments show good results demonstrating a reliable method for fetal brain data and the possibility of obtaining a parcellation of the fetal cortical surfaces using only geometrical features. PMID- 27413247 TI - The interaction between temperament and the family environment in adolescent substance use and externalizing behaviors: Support for diathesis-stress or differential susceptibility? AB - Both individual and environmental factors predict externalizing behaviors and substance use (EB-SU); however, different patterns of interaction among these factors may have different implications. This review first examines how temperament and the family environment interact in the prediction of adolescent EB-SU. Second, studies are reviewed according to two theoretical models: (1) diathesis-stress, i.e., certain individual characteristics are linked to vulnerability and later problems in adverse environments; (2) differential susceptibility, i.e., these characteristics are linked to susceptibility, predicting problems in adverse environments, but also better than average outcomes in good environments. Fourteen studies focusing on the prediction of EB SU at ages 12-18 were selected through a literature search. Results showed that certain temperament traits (high levels of impulsivity and disinhibition; low levels of effortful control, negative affect, fearfulness and shyness), hereby designated as "adventurous" disposition, were associated with higher levels of EB SU in adverse family environments. Some studies also showed that children with "adventurous" temperament traits in positive environments had the lowest levels of EB-SU. This suggests that prevention of EB-SU might target family factors such as parenting and focus on children with "adventurous" temperament traits. Further, studies that supported the differential susceptibility model were those assessing temperament and the family environment in childhood and studies that supported the diathesis-stress model assessed these variables in adolescence. It is thus possible that some of these "adventurous" temperament traits, with regard to EB-SU, would be indicators of susceptibility to both enriched and adverse environments in childhood but no longer in adolescence, when they would only be indicators of vulnerability to adverse environments. PMID- 27413249 TI - Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula. AB - Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis. PMID- 27413251 TI - Diagnostic Accuracy of Five Different Fecal Markers for the Detection of Precancerous and Cancerous Lesions of the Colorectum. AB - Background. Colorectal cancer (CRC) is the second deadliest malignancy worldwide. This study aimed to compare the diagnostic accuracy of different fecal markers in the detection of colorectal adenomas and cancer. Methods. Stool samples of patients referred to colonoscopy were collected for the analysis of tumor M2 pyruvate kinase (M2PK), human hemoglobin (Hb), hemoglobin/haptoglobin (Hb/Hp) complex, fecal calprotectin (FC), and matrix metalloproteinase-9 (MMP-9). Results. Sensitivity and specificity of M2PK for adenomas sized > 1 cm were 60% and 67.5% and for CRC were 94.7% and 67.5%. Sensitivity and specificity of iFOBT for adenomas sized >= 1 cm were 80% and 72.5% and for CRC were 94.7% and 72.5%. Sensitivity and specificity of Hb/Hp complex for adenomas sized >= 1 cm were 80% and 52.9% and for CRC were 100% and 52.9%. Sensitivity of FC and MMP-9 for CRC was 77.8% and 72.2%. Combined use of M2PK, iFOBT, and FC resulted in a sensitivity and specificity of 95% and 47.5% for the detection of adenomas sized >= 1 cm. Discussion. In CRC, sensitivity of M2PK, iFOBT, and Hb/Hp complex proved to be high. Combined use of M2PK, iFOBT, and FC may be valuable in the detection of large adenomas. PMID- 27413250 TI - Kruppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast Like Synoviocytes through Increased IL-6 Expression. AB - Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Kruppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Kruppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Kruppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Kruppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-alpha. Overexpression of Kruppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor alpha. Conversely, knockdown of Kruppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor alpha. Kruppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Kruppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-alpha. PMID- 27413252 TI - The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock. AB - Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p = 0.01). The expression of CD64 on circulating and airway neutrophils was similar (p = 0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p = 0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization. PMID- 27413253 TI - Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders. AB - Insulin resistance and other risk factors for atherosclerosis, such as hypertension and hypercholesterolemia, promote endothelial dysfunction and lead to development of metabolic syndrome which constitutes an introduction to cardiovascular disease. The insulin resistance and endothelial dysfunction cross talk between each other by numerous metabolic pathways. Hence, targeting one of these pathologies with pleiotropic treatment exerts beneficial effect on another one. Combined and expletive treatment of hypertension, lipid disorders, and insulin resistance with nonpharmacological interventions and conventional pharmacotherapy may inhibit the transformation of metabolic disturbances to fully developed cardiovascular disease. This paper summarises the common therapeutic targets for insulin resistance, endothelial dysfunction, and vascular inflammatory reaction at molecular level and analyses the potential pleiotropic effects of drugs used currently in management of cardiovascular disease, metabolic syndrome, and diabetes. PMID- 27413254 TI - Balancing Inflammation: The Link between Th17 and Regulatory T Cells. AB - CD4(+) T cell compartments in mouse and man are composed of multiple distinct subsets each possessing unique phenotypic and functional characteristics. IL-17 producing CD4(+) T cells (Th17 cells) represent a distinct subset of the CD4(+) T cell lineage. Recent evidence suggests that Th17 cells carry out effector functions similar to cytotoxic CD8(+) T cells and play an important role in the clearance of extracellular pathogens and fungi. Th17 cell differentiation and function are closely related to the development and function of regulatory T cells (TREG). The balance between these two cell populations is essential for immune homeostasis and dysregulation of this balance has been implicated in a variety of inflammatory conditions including autoimmunity, allograft rejection, and tumorigenesis. Emerging evidence reports a significant amount of plasticity between the Th17 and regulatory T cell compartments, and the mechanisms by which these cells communicate and influence each other are just beginning to be understood. In this review, we highlight recent findings detailing the mechanisms driving Th17 and TREG plasticity and discuss the biologic consequences of their unique relationship. PMID- 27413255 TI - Expression Profile of Cationic Amino Acid Transporters in Rats with Endotoxin Induced Uveitis. AB - Purpose. The transcellular arginine transportation via cationic amino acid transporter (CAT) is the rate-limiting step in nitric oxide (NO) synthesis, which is crucial in intraocular inflammation. In this study, CAT isoforms and inducible nitric oxide synthase (iNOS) expression was investigated in endotoxin-induced uveitis (EIU). Methods. EIU was induced in Lewis rats by lipopolysaccharide (LPS) injection. In the treatment group, the rats were injected intraperitoneally with the proteasome inhibitor bortezomib before EIU induction. After 24 hours, leukocyte quantification, NO measurement of the aqueous humor, and histopathological examination were evaluated. The expression of CAT isoforms and iNOS was determined by reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence staining. Nuclear factor-kappa B (NF-kappaB) binding activity was evaluated by electrophoretic mobility shift assay. The mouse macrophage cell line RAW 264.7 was used to validate the in vivo findings. Results. LPS significantly stimulated iNOS, CAT-2A, and CAT-2B mRNA and protein expression but did not affect CAT-1 in EIU rats and RAW 264.7 cells. Bortezomib attenuated inflammation and inhibited iNOS, CAT-2A, and CAT-2B expression through NF-kappaB inhibition. Conclusions. CAT-2 and iNOS, but not CAT-1, are specifically involved in EIU. NF-kappaB is essential in the induction of CAT-2 and iNOS in EIU. PMID- 27413256 TI - Effect of Toll-Like Receptor 4 on Synovial Injury of Temporomandibular Joint in Rats Caused by Occlusal Interference. AB - Synovitis is an important disease that causes intractable pain in TMJ. Some investigations suggested that the increasing expression of IL-1beta secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In our previous research, the results demonstrated that TLR4 is involved in the expression of IL-1beta in SFs from TMJ with lipopolysaccharide stimulation. However, the inflammatory response that occurred in synovial membrane is not caused by bacterial infection. In the current study, we investigated whether or not TLR4 participates in the inflammatory responses and the expression of IL-1beta in synovial membrane of rats induced by occlusal interference. The results showed that obvious inflammation changes were observed in the synovial membranes and the expression of TLR4 and IL-1beta was increased at both mRNA and protein levels in the occlusal interference rats. In addition, the inflammation reactions and the increased expression of IL-1beta could be restrained by treatment with TAK-242, a blocker of TLR4 signaling. The results prompted us that the activation of TLR4 may be involved in the inflammatory reactions and increased expression of IL-1beta in patients with synovitis and participate in the mechanisms of the initiation and development of synovial injury by regulating the expression of inflammatory mediators like IL-1beta in synovial membranes. PMID- 27413257 TI - Triptolide Inhibits Osteoclast Differentiation and Bone Resorption In Vitro via Enhancing the Production of IL-10 and TGF-beta1 by Regulatory T Cells. AB - Triptolide, a purified component of Tripterygiumwilfordii Hook F, has been shown to have immunosuppressive and anti-inflammatory properties in rheumatoid arthritis (RA). Although triptolide has demonstrated that it could suppress bone destruction in collagen-induced mice, its therapeutic mechanism remains unclear. Many studies have investigated the effect of triptolide on Tregs and Tregs related cytokine involved in RA. Additionally, previous studies have implied that Tregs inhibit osteoclast differentiation and bone resorption. Thus, in this study we aimed to explore the regulatory mechanism by which triptolide influences the Treg-mediated production of IL-10 and TGF-beta1 to affect osteoclast differentiation and bone resorption. In cocultures system of Tregs and mouse bone marrow macrophages (BMMs), Tregs inhibited the differentiation of osteoclasts and reduced the resorbed areas significantly and the production of both IL-10 and TGF beta1 was upregulated. When the coculture systems were pretreated with triptolide, they produced higher levels of IL-10 and TGF-beta1. Our data indicate that triptolide enhances the suppressive effects of Tregs on osteoclast differentiation and bone resorption by enhancing the secretion of IL-10 and TGF beta1. Tregs are most likely involved in the triptolide-mediated regulation of bone metabolism and may provide a potential therapeutic target for the treatment of inflammatory bone destruction. PMID- 27413258 TI - Infusion of Hibiscus sabdariffa L. Modulates Oxidative Stress in Patients with Marfan Syndrome. AB - Marfan syndrome (MFS) is associated with progressive aortic dilatation, endothelial dysfunction, and oxidative stress that contribute to the early acute dissection of the vessel and can end up in rupture of the aorta and sudden death. Many studies have described that the organic acids from Hibiscus sabdariffa Linne (HSL) calyces increase cellular antioxidant capacity and decrease oxidative stress. Here we evaluate if the antioxidant properties of HSL infusion improve oxidative stress in MFS patients. Activities of extra cellular super oxide dismutase (ECSOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSSG-R), glutathione (GSH), lipid peroxidation (LPO) index, total antioxidant capacity (TAC), and ascorbic acid were determined in plasma from MFS patients. Values before and after 3 months of the treatment with 2% HSL infusion were compared in control and MFS subjects. After treatment, there was a significant decrease in ECSOD (p = 0.03), EGPx (p = 0.04), GST (p = 0.03), GSH (p = 0.01), and TAC and ascorbic acid (p = 0.02) but GSSG-R activity (p = 0.04) and LPO (p = 0.02) were increased in MFS patients in comparison to patients receiving the HSL treatment and C subjects. Therefore, the infusion of HSL calyces has antioxidant properties that allow an increase in antioxidant capacity of both the enzymatic and nonenzymatic systems, in the plasma of the MSF patients. PMID- 27413259 TI - PGC-1alpha-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2 Induced Activities in Human NK Cells. AB - Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in antitumor defense reactions. NK cell effector functions are critically dependent on cytokines and metabolic activity. Among various cytokines modulating NK cell function, interleukin-2 (IL-2) can induce a more potent cytotoxic activity defined as lymphokine activated killer activity (LAK). Our aim was to determine if IL-2 induces changes at the mitochondrial level in NK cells to support the bioenergetic demand for performing this enhanced cytotoxic activity more efficiently. Purified human NK cells were cultured with high IL-2 concentrations to develop LAK activity, which was assessed by the ability of NK cells to lyse NK-resistant Daudi cells. Here we show that, after 72 h of culture of purified human NK cells with enough IL-2 to induce LAK activity, both the mitochondrial mass and the mitochondrial membrane potential increased in a PGC 1alpha-dependent manner. In addition, oligomycin, an inhibitor of ATP synthase, inhibited IL-2-induced LAK activity at 48 and 72 h of culture. Moreover, the secretion of IFN-gamma from NK cells with LAK activity was also partially dependent on PGC-1alpha expression. These results indicate that PGC-1alpha plays a crucial role in regulating mitochondrial function involved in the maintenance of LAK activity in human NK cells stimulated with IL-2. PMID- 27413260 TI - Teleradiology- a cyber cafe approach. PMID- 27413261 TI - Intestinal tuberculosis versus crohn's disease: Clinical and radiological recommendations. AB - Intestinal tuberculosis is a common clinical problem in India. The clinical features of this disease are nonspecific and can be very similar to Crohn's disease. Radiological evaluation of the small bowel has undergone a paradigm shift in the last decade. This long tubular organ that has traditionally been difficult to evaluate can now be well-visualized by some innovative imaging and endoscopic techniques. This article highlights the state-of-the-art evaluation of ulceroconstrictive diseases of the bowel and provides recommendations for the differentiation of intestinal tuberculosis from Crohn's disease. PMID- 27413263 TI - MDCT evaluation of sternal variations: Pictorial essay. AB - Sternal variations and anomalies have been identified in the past during autopsy or cadaveric studies. Recently, an increasing number of minor sternal variations have been reported with the advent of multidetector computed tomography (CT). Although there are many sternal variations that occur with varying appearance and prevalence, most of them are not recognized or are underreported during routine imaging of thorax. Identification of sternal variations is important to differentiate from pathological conditions and to prevent fatal complications prior to sternal interventions like marrow aspiration or acupuncture. This article aims to describe the minor and asymptomatic sternal variations by multidetector CT and their clinical significance. PMID- 27413262 TI - Magnetic resonance enterography: A stepwise interpretation approach and role of imaging in management of adult Crohn's disease. AB - Crohn's disease (CD) is a chronic inflammatory bowel disease that often requires frequent imaging of patients in order to detect active disease and other complications related to disease activity. While endoscopy is the gold standard for diagnosis, it may be contraindicated in some patients and has a limited role in detecting deep submucosal/mesenteric diseases and intra abdominal complications. In recent years, magnetic resonance enterography (MRE) has evolved as a noninvasive, radiation free imaging modality in the evaluation of patients with CD. This review article will focus on role of MRE in imaging patients with CD with emphasis on technical considerations, systematic image interpretation, differential diagnoses, and the role of imaging in deciding treatment options for patients. PMID- 27413264 TI - Pulmonary arteriovenous malformation in chronic thromboembolic pulmonary hypertension. AB - Chronic thromboembolic pulmonary hypertension is a morbid condition associated with complications such as hemoptysis, right heart failure, paradoxical embolism, and even death. There is no known association of chronic thromboembolic pulmonary hypertension with pulmonary arteriovenous malformation. Possible hypothesis for this association is an increased pulmonary vascular resistance leading to the compensatory formation of pulmonary arteriovenous malformation. We present one such case presenting with hemoptysis that was managed with endovascular treatment. PMID- 27413265 TI - Computed tomography coronary angiography diagnosis of single right coronary artery with congenital absence of left coronary artery system equivalents. AB - The present case report is computed tomography (CT) coronary angiographic depiction of an exceedingly rare entity-single right coronary artery arising from the right sinus of Valsalva with the absence of equivalent left coronary artery system branches and associated mitral valve prolapse. Even though a statistical rarity, it is potentially fatal and can cause myocardial ischemia, sudden cardiac death, and warrants immediate clinical attention. Further, the report reveals the decisive role of CT coronary angiogram in the diagnosis of such rare entities, in contrast to catheter angiography, which may be inconclusive. PMID- 27413266 TI - Dual left anterior descending artery with anomalous origin of long LAD from pulmonary artery - rare coronary anomaly detected on computed tomography coronary angiography. AB - Dual left anterior descending artery is a rare coronary artery anomaly showing two left anterior descending arteries. Short anterior descending artery usually arises from the left coronary artery, while long anterior descending artery has anomalous origin and course. Dual left anterior descending artery with origin of long anterior descending artery from the pulmonary artery (ALCAPA) is a very rare coronary artery anomaly which has not been reported previously in the literature. We present the computed tomography coronary angiographic findings of this rare case in a young female patient who presented with atypical chest pain. PMID- 27413267 TI - A rare case of esophageal lung in a neonate. AB - We report a rare case of esophageal lung in a neonate who presented with repeated chest infections and respiratory distress. Chest radiograph revealed increased opacification of the right lung with reduced lung volume and air bronchograms. Further evaluation with computed tomography (CT) showed the presence of only left mainstem bronchus at the tracheal bifurcation. Right mainstem bronchus originated from distal esophagus and aerated the right lung. Nasogastric tube was inserted into the stomach with injection of small amount of dilute barium through it, which established the communication of right mainstem bronchus with esophagus. Advanced CT scan imaging by virtual bronchoscopy and volume rendering further delineated the anatomical abnormality precisely prior to surgery. Surgical findings confirmed the diagnosis. PMID- 27413268 TI - Characterization of lesions in dense breasts: Does tomosynthesis help? AB - CONTEXT: Mammography in dense breasts is challenging due to lesion obscuration by tissue overlap. Does tomosynthesis offers a solution? AIMS: To study the impact of digital breast tomosynthesis (DBT) in characterizing lesions in breasts of different mammographic densities. SETTINGS AND DESIGN: Prospective blinded study comparing mammography in two views with Mammography + Tomosynthesis. METHODS AND MATERIAL: Tomosynthesis was performed in 199 patients who were assigned Breast imaging reporting and data system (BIRADS) categories 0, 3, 4, or 5 on two dimensional (2D) mammogram. Mammograms were first categorized into one of 4 mammographic breast densities in accordance with the American College of Radiology (ACR). Three radiologists independently analyzed these images and assigned a BIRADS category first based on 2D mammogram alone, and then assigned a fresh BIRADS category after taking mammography and tomosynthesis into consideration. A composite gold-standard was used in the study (histopathology, ultrasound, follow-up mammogram, magnetic resonance imaging). Each lesion was categorized into 3 groups-superior categorization with DBT, no change in BIRADS, or inferior BIRADS category based on comparison with the gold-standard. The percentage of lesions in each group was calculated for different breast densities. RESULTS: There were 260 lesions (ages 28-85). Overall, superior categorization was seen in 21.2% of our readings on addition of DBT to mammography. DBT was most useful in ACR Densities 3 and 4 breasts where it led to more appropriate categorization in 27 and 42% of lesions, respectively. DBT also increased diagnostic confidence in 54.5 and 63.6% of lesions in ACR Densities 3 and 4, respectively. CONCLUSIONS: In a diagnostic setting, the utility of tomosynthesis increases with increasing breast density. This helps in identifying the sub category of patients where DBT can actually change management. PMID- 27413269 TI - Imaging of common breast implants and implant-related complications: A pictorial essay. AB - The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer. PMID- 27413270 TI - Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of breast. AB - Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor that is morphologically indistinguishable from skeletal ES. We report a case of a 25-year old female with recurrent EES/primitive neuroectodermal tumor of right breast with imaging findings on mammogram, ultrasound, magnetic resonance imaging breast, and positron emission tomography-computed tomography. PMID- 27413271 TI - Diffusion-weighted imaging in extracranial head and neck schwannomas: A distinctive appearance. AB - PURPOSE: To evaluate the diffusion weighted (DW) magnetic resonance imaging (MRI) features of the extracranial schwannomas of head and neck. MATERIALS AND METHODS: The MRI (including DWI) of 12 patients with pathologically proven head and neck schwannomas (4 men, 8 women, with mean age of 32.6 years; age range 16-50 years) were retrospectively evaluated. Images were analyzed for signal intensity and morphology on conventional sequences followed by the qualitative evaluation of DW images (DWI) and measurement of apparent diffusion coefficient (ADC) values. RESULTS: Majority of the tumors were located in the parapharyngeal space (8/12). All but one showed heterogeneous appearance, with 10 tumors showing scattered areas of hemorrhage. Eight out of 12 tumors showed intensely hyperintense core surrounded by intermediate signal intensity peripheral rim (reverse target sign) on T2-weighted (T2W) images. On DWI, these eight tumors showed a distinctive appearance, resembling target sign on trace DWI and reverse target on ADC map. Out of the remaining four tumors, one showed uniformly restricted diffusion whereas three showed free diffusion. Mean ADC value in the central area of free diffusion was 2.277 * 10(-3) mm(2)/s (range of 1.790 * 10 -(3) to 2.605 * 10(-3) mm(2)/s) whereas in the peripheral area was 1.117 * 10(-3) mm(2)/s (range of 0.656 * 10(-3) to 1.701 * 10(-3) mm(2)/s). Rest of the schwannomas showing free diffusion had a mean ADC value of 1.971 * 10(-3) mm(2)/s. CONCLUSION: Majority of the head and neck schwannomas showed a characteristic appearance of free diffusion in the centre and restricted diffusion in the periphery of the mass. PMID- 27413272 TI - Spontaneous external auditory canal cholesteatoma in a young male: Imaging findings and differential diagnoses. AB - A cholesteatoma is a non-neoplastic lesion of the petrous temporal bone commonly described as "skin in the wrong place." It typically arises within the middle ear cavity, may drain externally via tympanic membrane (mural type), or may originate in the external auditory canal (EAC). The latter type is rarely encountered and typically affects the elderly. EAC cholesteatoma poses diagnostic challenges because it has numerous differential diagnoses. The present case describes a 19 year-old male who presented with gradually progressive diminution of hearing in a previously naive right ear since 8 months. A soft tissue attenuation lesion confined to the right EAC with erosion of the canal on computed tomography prompted magnetic resonance imaging (MRI). The lesion showed restricted diffusion on MRI. Thus, a diagnosis of spontaneous EAC cholesteatoma was established. The case elucidates the rarity of spontaneous EAC cholesteatoma in a young male. In addition, it describes the role of imaging to detect, delineate the extent, and characterize lesions of petrous temporal bone. The case also discusses common differential diagnoses of EAC cholesteatoma, as well as the importance of diffusion weighted imaging in EAC cholesteatoma similar to its middle ear counterpart. PMID- 27413273 TI - Bilateral nasolabial cysts - case report and review of literature. AB - Nasolabial cyst is a non-odontogenic, extraosseous, soft tissue cyst, commonly unilateral, located in the nasolabial fold. Bilateral nasolabial cysts are of rare occurrence. This case report describes the multimodality imaging appearance of bilateral nasolabial cysts with a review of literature. PMID- 27413274 TI - Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland. AB - Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID- 27413275 TI - OUTBACK catheter for treatment of superficial femoral and iliac artery chronic total occlusion: Experience from two centers. AB - PURPOSE: The OUTBACK((r)) catheter is a reentry device that enables reentry into a vessel lumen from the subintimal space during subintimal angioplasty. It is reserved for cases where reentry has not been possible using conventional wire and catheter techniques. We report a two-center experience in recanalization of the chronic total occlusions of the common iliac (CIA) and the superficial femoral artery (SFA) using the OUTBACK((r)) catheter in cases where other techniques were unsuccessful. MATERIAL AND METHODS: All cases where recanalization was performed using the OUTBACK((r)) reentry catheter between January 2010 to January 2015 were retrospectively identified and included in this study. 21 patients were identified. The indication for intervention in these cases included claudication and critical leg ischemia. In all cases, conventional recanalization could not be successfully achieved. RESULTS: The OUTBACK((r)) catheter was used to recanalize 10 SFA occlusion and 9 CIA occlusions. In 19 patients (90%), reentry into true arterial lumen was successfully achieved. 17 patients had their recanalization through the transfemoral approach whereas 2 patients had a transpopliteal artery approach. In 2 patients, reentry into the true lumen could not be achieved using the OUTBACK((r)) catheter due to patient's intolerability for the procedure and severe atherosclerotic calcified plaques. There was 100% patency of the vessel intervened on Duplex ultrasound at 24 months of follow up. 16 patients (84%) remained asymptomatic and 2 patients (10.5%) reported worsening of their symptoms due to the development of new lesions within the arterial system. CONCLUSION: The OUTBACK((r)) catheter is an effective and safe technique for reentry into the vessel lumen when conventional techniques fail. PMID- 27413276 TI - Amplatzer vascular plug as an embolic agent in different vascular pathologies: A pictorial essay. AB - The Amplatzer Vascular Plug (AVP) is a cylindrical plug made of self-expanding nitinol wire mesh with precise delivery control, which can be used for a variety of vascular pathologies. An AVP is an ideal vascular occlusion device particularly in high-flow vessels, where there is high risk of migration and systemic embolization with traditional occlusion devices. We performed 28 embolizations using the AVP from 2009 to 2014 and achieved complete occlusion without complications. PMID- 27413277 TI - Percutaneous repair of iatrogenic subclavian artery injury by suture-mediated closure device. AB - Central venous catheterization through internal jugular vein is done routinely in intensive care units. It is generally safe, more so when the procedure is performed under ultrasound guidance. However, there could be inadvertent puncture of other vessels in the neck when the procedure is not performed under real-time sonographic guidance. Closure of this vessel opening can pose a challenge if it is an artery, in a location difficult to compress, and is further complicated by deranged coagulation profile. Here, we discuss the removal of an inadvertently placed catheter from subclavian artery with closure of arteriotomy percutaneously using arterial suture-mediated closure device. PMID- 27413278 TI - Recurrent hemoptysis: An unusual cause and novel management. AB - We report a rare case a 15 year old boy who presented with recurrent hemoptysis. There was past history of pancreatitis. A CT scan of thorax revealed a small collection in the region of the tail of the pancreas and a tract from it extending across the diaphragm into the posterobasal segment of left lower lobe, suggesting a pancreatico-pleuro-pulmonary fistula. The fistula was embolised by percutaneous injection of glue into the collection and fistula, which resulted in good symptom control. PMID- 27413279 TI - Magnetic resonance imaging features of complications following hip replacement: A pictorial review. AB - Hip replacement surgery helps millions of people worldwide walk painlessly each year. With increasing life spans and decreased clinical threshold for surgery, this number will continue to rise. With the increase in the number of surgeries and the longevity of implants, the need for early and prompt diagnosis of complications is also rising. This essay underlines the fact that magnetic resonance imaging on a 1.5T scanner with specialized metal artefact reduction sequences is a viable technique to image the post-arthroplasty hip and has vast potential in the prompt and early diagnosis of complications in these patients. PMID- 27413280 TI - Imaging features of primary tumors of the spine: A pictorial essay. AB - Primary tumors of spine are rare accounting for less than 5% of new bone tumors diagnosed every year. These tumors may exhibit characteristic imaging features that can help in early diagnosis and improved prognosis. Plasmacytoma/multiple myeloma and lymphoproliferative tumors are the most common malignant primary spinal tumors. Hemangioma is the most common benign tumor of the spine. Computed tomography is useful to assess tumor matrix and osseous change. Magnetic resonance is useful to study associated soft tissue extension, marrow infiltration, and intraspinal extension. Confusing one tumor with the other based on only imaging findings is not uncommon. However, radiologic manifestations of these tumors need to be correlated with the age, sex, location, and presentation to arrive at a close clinical diagnosis. PMID- 27413281 TI - Osteofibrous dysplasia of clavicle clinically mimicking chronic osteomyelitis. AB - Osteofibrous dysplasia or ossifying fibroma is an uncommon benign fibro-osseous lesion of childhood, commonly described in the maxilla and the mandible. Among long bones, it usually presents in the tibia as a painless swelling or anterior bowing. Ossifying fibroma of clavicle has never been reported in English literature, to the best of our knowledge. Here, we would like to present an unusual case of osteofibrous dysplasia of clavicle clinically mimicking chronic osteomyelitis. PMID- 27413283 TI - Prevalence of gastrointestinal parasites in dogs of Palampur, Himachal Pradesh. AB - A total of 246 faecal/scat samples of the dogs were screened by direct and floatation concentration technique to study the gastrointestinal (GI) tract parasitism in dogs of Palampur, Himachal Pradesh, India. Detailed coprological examination targeting different seasons, age groups and living styles of the dogs revealed an overall 28.04 % of GI parasitism with highest prevalence in summer season (37.87 %). Stray dogs harbored 47.29 % GI parasites in comparison to 19.19 % of pet dogs. Highest prevalence of GI parasitism was observed in the pups, below 3 months of age (39.13 %), followed by the dogs with the age ranging from 3 months to 1 year (26.38 %) and lowest in dogs of the age ranging from 1 to 3 years (6.77 %). Amongst all the parasites, Toxocara canis (44.93 %) infection was highest, followed by Dipylidium caninum (17.39 %) and hookworms (15.94 %). PMID- 27413282 TI - Parasites and immunotherapy: with or against? AB - Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewed. PMID- 27413284 TI - Biochemical studies of M. incognita and M. javanica towards their identification. AB - Biochemical analysis is a reliable, quick, yet effective way for profiling any organism. The same tools when employed in taxonomic queries, they aid substantially and support the process. Taxonomic queries have been since beginning presenting numerable challenges towards the studies of different plant parasitic nematodes. In the present study various biochemical tests have been employed to assess the differentiation among the two dominant sps. of Meloidogyne i.e., M. incognita and M. javanica. Some of the biochemical parameters considered were the specific concentrations of carbohydrates and cholesterol and were monitored in the juvenile and the female of the respective species. Results have been discussed in details along with its employability towards the taxonomical studies especially with reference to plant parasitic nematodes. PMID- 27413285 TI - Morphological characterization of Cysticercus cellulosae in naturally infected pigs in Punjab (India). AB - Porcine cysticercosis is an important medical and veterinary concern in the developing world. The present study was carried out to determine the morphological characteristics of Cysticercus cellulosae, so as to differentiate the C. viscerotropica (larval form of T. asiatica) which is having only rudimentary hooks on their rostellum. Morphological analysis was conducted on 22 Cysticercus positive samples. Measurements for number of hooks (large and small), the total length and blade length of large and small hooks per rostellum were carried out as per previous studies. Microscopic examination of all the cysts showed typical characteristic of T. solium i.e. presence of hooks in all the cysts. The results indicated absence of T. asiatica from naturally infected pigs in Punjab (India). PMID- 27413286 TI - Estimation of loss and analysis of nicotine, reducing sugar and chloride in bidi tobacco due to reniform nematode under pot conditions. AB - Estimation of avoidable loss in yield of bidi tobacco due to reniform nematode under pot conditions revealed that variety A 119 suffered heavily than ABT 10 due to reniform nematode. Inoculation of reniform nematode @ 2000 J4 per plant significantly reduced the plant growth characters and increased nematode multiplication preferring A 119 variety. Estimation of avoidable loss in cured shoot yield of bidi tobacco due to infection of reniform nematode in individual variety ABT 10 and A 119 has been estimated to the tune of 30.5 and 34.2 per cent with overall loss 31.9 per cent in both the variety 60 DAI. Simply growing of ABT 10 variety irrespective of infection of reniform nematode avoided 29.5 per cent loss in cured shoot yield. ABT 10 recorded significantly high nicotine, reducing sugar and chloride than A 119; inoculation of reniform nematode significantly increased nicotine, reducing sugar and chloride compared to no inoculation. Interaction indicated that inoculation of 2000 J4 of reniform nematode significantly increased nicotine, reducing sugar and chloride in A 119 compared to no inoculation; while significantly reduced reducing sugar and increased chloride in ABT 10. There was no significant impact of infection of reniform nematode on nicotine in ABT 10. PMID- 27413287 TI - Ultrasonographic changes in dogs naturally infected with tick borne intracellular diseases. AB - Tick-borne infectious diseases constitute an emerging problem in Veterinary Medicine. The study was undertaken to find out the ultrasonographic changes of liver and spleen in 101 positive cases of tick borne intracellular haemoparasitic diseases in dogs. Abdominal survey of ultrasonography revealed hypo echogenicity of liver, gall bladder distension, splenomegaly, hepato-splenomegaly and ascites in various tick born intracellular diseases viz. ehrlichiosis, babesiosis, anaplasmosis, hepatozoonosis and in mixed infection. Correlating these USG finding with other laboratory examination will be very much useful to spot the diseases condition and organ involvement in tick born intracellular diseases of dog. PMID- 27413288 TI - Pimply gut condition in mithun (Bos frontalis) calves. AB - The present observation was recorded at National Research Centre on Mithun, Jharnapani from May 2010 to September 2012. A total of 15 mithun calves, which died in and around Jharnapani, were attended and detailed post-mortem examination was carried out. Out of these, five calves (33.33 %) aging between 1 and 1.5 years exhibiting the condition of chronic wasting and diarrhoea were found positive for pimply gut condition based on gross and microscopic examination. Post-mortem examination revealed extensive nodule formation on the wall of the rectum; however, the entire lumen did not reveal any of adult parasites. In all the cases, there were congestion in the mucous layer and thickening of the intestinal wall. Histopathological examination revealed chronic enteritis with mononuclear cell infiltration comprising mostly of macrophages, lymphocytes and eosinophils. In the muscularis mucosae, encysted larvae were found along with fibrous tissue proliferation. These lesions gave the intestine a nodular appearance as they thickened the wall and projected from the serosal surface. These extensive numbers of nodules in the intestine might have interfered with peristalsis and intestinal absorption which led to chronic wasting and diarrhoea in the calves. PMID- 27413289 TI - Histopathological and morphological studies on natural Cysticercus fasciolaris infection in liver of Wistar rats. AB - Descriptive morphology of multifocal hepatic cysts found in eight of forty five (17.78 %) Wistar rats sacrificed during pharmacological studies related to herbal formulations was studied. The creamish to white cysts were of varying sizes, ranging from 3-8 mm in diameter. Morphological studies of these cysts depicted the presence of metacestodes of Taenia taeniaeformis i.e. Cysticercus fasciolaris inside them. The scolex of metacestode revealed four suckers and rostellum armed with two distinct rows of characteristic pen knife shaped hooks (characteristics of taeniid cestodes). The average size of large hooks was 392.92 +/- 10.12 u and that of small hooks was 240.64 +/- 14.26 u. The average size of suckers was 304.36 +/- 12.33 u. Histopathology of hepatic tissue surrounding the cysts revealed zones of fatty change, inflammation, granulation tissue and metaplasia. However, the histopathology of stomach and small intestines didn't show any significant lesions. PMID- 27413290 TI - Therapeutic effect of mefloquine on Schistosoma mansoni in experimental infection in mice. AB - Schistosomiasis is one of the most prevalent parasitic infections worldwide. Praziquantel is the drug of choice for treatment of schistosomiasis for its high efficacy. The present work was carried out on 160 mice to evaluate the therapeutic effect of mefloquine on experimental schistosomiasis mansoni. Mice were classified into 3 groups; group I (20 infected non-treated mice), group II included 60 infected mice which were further divided into group IIm (20 mice treated with 400 mg/kg mefloquine), group IIp (20 mice treated with 1,000 mg/kg/2 days praziquantel) and group IIpm (20 mice treated with 200 mg/kg mefloquine and 500 mg/kg praziquantel), group III included 80 non-infected mice subdivided into group IIIn (20 non-treated mice), group IIIm (20 mice treated with 400 mg/kg mefloquine), group IIIp (20 mice treated with 1,000 mg/kg/2 days praziquantel), group IIIpm (20 mice treated with 200 mg mefloquine and 500 mg praziquantel). Mefloquine significantly reduced worm burden, tissue egg load, number of liver granulomas and increased the percent of dead ova within granulomas. Combination of mefloquine and praziquantel gave better curative effects than praziquantel or mefloquine given alone. PMID- 27413291 TI - Clinical and laboratory findings of Babesia infection in dogs. AB - Canine babesiosis is a worldwide tick borne disease. Dogs with fever, in appetence and enlarged lymph nodes were screened for the presence of haemoprotozoan parasites during the one year period of study at T.V.C.C., C.V.Sc., Proddatur. Based on the stained peripheral blood smears examination, six dogs were found to be affected with babesiosis. Clinical examination of the dogs revealed ticks over the body, congested conjunctival mucus membranes, dullness, fever, tachycardia, tachypnoea in all the dogs. Some of the dogs had icterus, lymphadenopathy, haemoglobinuria. Laboratory examination of the clinical samples revealed reduction in haemoglobin concentration, erythrocyte count, platelet count, serum total protein, serum albumin and glucose levels. Increased serum SGPT, creatinine, BUN levels were recorded. Dogs were treated with inj. Diminazene aceturate (Berenil RTU) @ 5 mg/kg body weight, single dose along with supportive and symptomatic therapy in individual cases. PMID- 27413292 TI - Parasitic fauna of Gobiidae in Mazandaran coastal zones, north of Iran 2011. AB - Gobiidae is considered as one of the diverse families of fishes in Caspian Sea. Due to abundant species and no harvest, this family plays an important role in ecology and feed chain of fishes in Caspian Sea. Present study was performed to determine parasitic fauna of Gobiidae in southern parts of Caspian Sea (coasts of Nowshahr, Sorkhrood, Jouybar, Sari and Amirabad). Primarily, length and weight of each fish was measured. Then, fish's various organs were examined by routine parasitology methods. From 150 fishes which were caught from six studied coastal zones, 51 (34 %) were infected. Majority of caught fishes was belonged to sand goby (Neogobius fluviatilis pallasi) and round goby (Neogobius melanostomus) was the least. Highest rate of infection was seen in N. fluviatilis pallasi while, this percentage in round goby (N. melanostomus) was low (8.57 %) and in Caspian bighead goby (Neogobius kessleri gorlap) no parasitic infection was observed. Most of infected fishes were from Jouybar coastal zone while Nowshahr coastal zone had the lowest infection rate. In present study parasites such as Dactylogyrus, Rhobdochona fortuneti and Bothrocephalus gowkogensis were diagnosed in Caspian gobies. Regarding importance of gobies in chain feed of other fishes and their indirect economic importance, need of diagnosing of gobies parasitic fauna seems to be essential. PMID- 27413293 TI - Lactate dehydrogenase (LD), alkaline phosphatase (ALP) isoenzymatic patterns in Iraqi children with visceral leishmaniasis before and after treatment with stibogluconate. AB - The mean levels of alkaline phosphatase (ALP), lactate dehydrogenase enzymes exhibited a significant elevation in visceral leishmaniasis (VL) patients compared to the control. There was no significant change in relation to the sex and age. ALP isoenzymes revealed three banding patterns which differ from the three zymodems which were obtained from control group. These differences may be due to isoenzymes activity of patients with VL before and after therapy. Lactate dehydrogenase (LD) isoenzymes revealed five banding patterns differ from the five normal zymodems. These differences mainly occurred due to LD isoenzymes activity in patients with VL before and after therapy. PMID- 27413294 TI - The role of sheep in the epidemiology of Sarcocystis spp. in Tabriz area northwest of Iran. AB - The parasites of genus Sarcocystis are among the most commonly found parasites in domestic ruminants and some species of Sarcocystis can generate important economic loss when causing clinical and subclinical disease. In the present study, three techniques-direct inspection, impression smears and digestion method were used for the diagnosis of Sarcocystis infection in 130 slaughtered sheep in Tabriz abattoir from April 2013 to October 2013. A total of 620 slaughtered sheep were selected randomly and their oesophagus and diaphragm were inspected using naked eye examination. In the second stage, 130 carcasses out of the 620 which had no apparent infection were selected randomly and their meat investigated using two techniques: impression smear with staining and pepsin digestion. The percentage of macroscopic cysts found in the oesophagus and diaphragm muscle was 5.64 and 2.74 %, respectively, and microscopically, infection was found in 100 % of the organs. There was no significant difference between different ages or between males and females. Although all of the sheep were found to be infected with Sarcocystis, majority of the cysts were demonstrated microscopically. This suggests that meat should be cooked sufficiently, since a macroscopic inspection may not provide true results. Also, it has of grea t importance the farmers to be trained not to feed their dogs and cats with uncooked meat, and the abattoir remnants to be burned, in order to be effectively broken of infection cycle between the intermediate and the definitive hosts in Tabriz city, northwest of Iran. PMID- 27413295 TI - Prevalence of Strongyle infections in goat of Maha Koushal region, Madhya Pradesh, India. AB - The coproculture study on Strongyle infection of goats was carried out in small holder farmers kept under semi-intensive management system in Balaghat, Narsinghpur and Chhindwara district, Madhya Pradesh, during the period from July 2011 to February 2012. Copro-culture of the samples positive for Strongyle infection revealed Haemonchus sp., Trichostrongylus sp., Oesophagostomum sp., Strongyloides sp., and Bunostomum sp. in a decreasing order in goats. The larvae of Haemonchus sp. (61.63 %) and Strongyloides sp. (7.50 %) were highest in Balaghat, Trichostrongylus (18.13 %) in Narsinghpur, while Oesophagostomum sp. (10.50 %) and Bunostomum sp. (5.75 %) were in Chhindwara district. The finding of this study indicates that, even though subclinical in nature, Strongyle infection are one of the major problems that could hamper health and productivity and there is need for design a programme to minimize and control Strongyle infection in goats in the study area. PMID- 27413296 TI - Electrophoretic pattern of Linguatula serrata larva isolated goat mesenteric lymph node. AB - Linguatula serrata, one of the parasitic zoonoses, inhabits the canid and felid respiratory system. The parasite is tongue-shaped, lightly convex dorsally and flattened ventrally. Males measure 1.8-2 cm, while females measure 8-13 cm in length. Disease due to infection with this parasite in humans is more likely to cause pharyngitis, nausea and vomiting, sore and itchy throat, cough, phlegm and runny nose. Present study aimed to determine linguatula's larva somatic antigens in lymph nodes of infected goats and also reveal the major component of antigenic protein. To determine the electrophoretic pattern of L. serrata's larvae, 50 samples were taken from goat's referred to the slaughter house of Amol, Mazandaran, Iran. After performing SDS-PAGE on somatic antigens, 6 bands (19, 20, 36, 48, 75,100 KDa) were seen in which the 36, 48 and 75 KDa bands were more prominent. In conclusion, it is recommended to determine the most important antigenic protein of this parasite could be used an experimental model in infection up to determine the most significant component of this parasite's antigen and use of that in immunogenicity and detection of infection. PMID- 27413298 TI - Epidemiological and diagnostic studies of microfilariasis in buffaloes. AB - A study was conducted to determine the prevalence of microfilariasis and analysis of diagnostic methods in buffaloes at Veterinary Poly Clinic, Gudiwada with relation to season, age and breed for a period of 1 year (March 2011-February 2012).Out of 1,222 blood smears examination, only 123 samples were found positive for microfilariasis with a prevalence rate of 10.06 %. Highest prevalence was observed in monsoon (12.54 %) followed by summer (9.18 %) and least in winter (7.05 %). Buffaloes above 9 years age were at high risk with a prevalence rate of 12.5 %, followed by 3-9 years (10.7 %) and below 3 years age (6.09 %) respectively. Breed wise prevalence of microfilariasis was higher in graded murrah buffaloes 10.87 % compared to non-descripts (6.19 %). Three commonly used diagnostic techniques viz. Modified Knott's Technique, thick blood smear examination and wet film examination were done to evaluate comparative sensitivity/efficacy. Among these techniques, 100 % efficacy was observed in Modified Knott's Technique and 86.99 % in thick blood smear examination followed wet film examination 78.04 % respectively. PMID- 27413297 TI - Gill histopathology of Maria-da-toca Hypleurochilus fissicornis by metacercariae of Bucephalus margaritae (Digenea: Bucephalidae). AB - Gills of Maria-da-toca Hypleurochilus fissicornis collected at Ponta do Sambaqui Florianopolis island-Brazil, were analyzed to describe the histopathology caused by metacercaria of Bucephalus margaritae. Gills were submitted to the routine histological techniques for embedding in paraffin and permanent mounting in Balsam and stereoscopic analysis. Metacercariae showed a branchial infection site pattern for encystations. The branchial infection site pattern is half-basalward in the primary branchial filament with amplitude of the infection of 1-3 metacercaria. Cysts occurred within branchial abductor muscle and cartilaginous and osseous tissues of the gills. Each metacercariae had a contentional hyaline parasitic capsule and melanin-like pigmentation. The half-apicalward region of the primary branchial filaments showed several dysplasia degrees, cartilage and osseous degeneration (pyknosis), thrombosis and immune exudated cells (mainly lymphocytes). Cytopathologies as thickening of the epithelium lining of the secondary branchial filaments were a response of the branchial infection site pattern of the metacercaria. Interlamellar obliteration and fusion of the lamellae due to the hypertrophy and hyperplasia of the epithelial lining as well as chloride cells occurred. Pyknosis of pillar cells and epithelial lining cells from the secondary branchial filaments were also present. Bucephalosis in H. fissicornis gills is no-hemorrhagic and no-fatal branchitis, but could compromises the gill functions and could permits the secondary opportunistic infections. PMID- 27413299 TI - Effect of Plasmodium falciparum malaria parasites on haematological parameters in Ghanaian children. AB - Malaria is hyper-endemic in Ghana. Haematological alterations in the disease pathology may offer complimentary criteria to improve clinical and microscopy diagnosis. Our primary outcome was to evaluate haematological parameters in children with Plasmodium falciparum infections and report their predictive risk and diagnostic performance for malaria infections in Ghana. Haematological data, including thin and thick blood films were examined for children less than 12 years of age in a multicenter-based active case finding approach. Haematological changes were common in P. falciparum infected children and more pronounced in severe malaria cases. More so, a unit increase in parasiteamia increased the odds for severe malaria infection by 93 % [OR, 95 % CI: 1.93 (1.28-2.91); P value = 0.02]. In multivariate regression, low haemoglobin was a significant haematological change in predicting P. falciparum infections [OR, 95 % CI: 3.20 (1.26-7.09); P value = 0.001]. Low haemoglobin levels <11 g/dl was the most reliable indicator for P. falciparum infections [with a sensitivity of (64 %), specificity (71 %), positive predictive value (83 %) and likelihood ratio (2.2)] even when evaluated in combination with leucocytosis, lymphocytopaenia and high neutrophil counts >7,500 uL. In malaria endemic settings, low haemoglobin concentration (<11 g/dl) in children with febrile illness should prompt a more diligent search for the malarial parasite to limit the misuse and abuse of anti malarial drugs. PMID- 27413300 TI - Helminth parasite spectrum of fishes in Meghalaya, Northeast India: a checklist. AB - Fish constitute a major component of diet for the people of Northeast India and they are extensively used as a protein-rich food for human consumption. The present studies incorporate the spectrum, composition and diversity of the parasitic species in freshwater fishes in Meghalaya, Northeast India, with a view to identifying the species recovered by morphological criteria based on light microscopy. The collection sites included sixteen foci from eleven districts of Meghalaya for parasites occurring in the common food fishes (Cypriniformes, Channiformes, Silurformes, Symbranchiformes and Anguilliformes). The helminth parasite spectrum recovered from the various piscine host species in the study area comprised of a total of 19 taxa: 2 monogenean, 8 trematode (4 adult and 4 metacercarial stages), 12 cestode (11 adult and a metacestode stage), 6 nematode (3 adult and 3 larval stages) and a single acanthocephalan species. A checklist of the parasite species with short remarks for each is provided herein. PMID- 27413301 TI - Utilizing ribosomal DNA gene marker regions to characterize the metacercariae (Trematoda: Digenea) parasitizing piscine intermediate hosts in Manipur, Northeast India. AB - Freshwater fishes in Manipur, Northeast India frequently harbour several types of metacercariae, which based on morphological criteria were identified as Clinostomoides brieni, Euclinostomum heterostomum (Clinostomidae) and Polylekithum sp. (Allocreadiidae). Molecular techniques utilizing PCR amplification of rDNA regions of larger subunit (LSU or 28S), smaller subunit (SSU or 18S) and inter transcribed spacers (ITS1, 2) were used for molecular characterization of these types. Sequences generated from the metacercariae were compared with their related sequences available in public databases; an analysis of the identity matrices and phylogenetic trees constructed was also carried out, which confirmed their identification. Similarly, the sequences generated from Polylekithum sp. were found to be highly similar to the species of the same genus. The rDNA ITS2 secondary structure provided additional confirmation of the robustness of the molecular marker as a tool for taxon-specific characterization. PMID- 27413302 TI - Prevalence, morphology and scanning electron microscopy study of myxozoan parasites. AB - The present study was conducted from Garia, West Bengal, India to study the Prevalence, Morphology, Severity of infestation and Scanning Electron Microscopy of Myxozoan parasites in Indian Major Carps. A total of 155 fishes were examined, out of which 80 were found infected with myxozoan parasites (51.61 %) and severity of infestation varied from 0.5 to 2. Three known species Myxobolus orissae, M. carnaticus and Thelohanellus caudatus were found infecting various organs such as gills and fins of Indian major carps. Spores of the species, T. caudatus measures 12.84 +/- 0.77 (11.4-14.2) MUm * 8.5 +/- 0.71 (7.6-9.6) MUm and was elongated pyriform in shape with rounded posterior and tappering anterior end. Parietal folds were absent. The single polar capsule is rounded to oval shaped with slightly pointed anterior end and broad posterior end with size measuring 6.15 +/- 2.09 (4.2-10.4) MUm * 3.85 +/- 1.18 (2.3-4.9) MUm. M. orissae, size of the mature spore measures 15.6-19.7 (17.25) MUm * 5.7-9.3 (6.70) MUm and was elongated pyriform in shape. Two polar capsules are distinctly unequal. Large one measures 6.8-13.5 (8.75) * 1.4-3.1 (1.90) MUm and smaller one 6.9-11.5 (7.44) * 1.7-2.4 (1.57) MUm in size. Both are broadly pyriform with pointed pointed anterior end and rounded posterior end. Myxobolus carnaticus mature histozoic spores measures 8.1-12.9 (9.49) * 7.2-10 (8.27) um are creamy white to yellow in colour tear shaped in valvular view with rounded posterior and bluntly pointed anterior ends. PMID- 27413303 TI - Bioinvasion: a paradigm shift from marine to inland ecosystems. AB - Anisakidosis is one of the most fearsome zoonotic food borne disease in aquaculture. The natural infections by anisakidoids or related variety in freshwater fish are not known, though sporadic experimental reports are available abroad (Butcher and Shamsi 2011). Invasive severity of anisakidoids in fish from Gangetic riverine ecosystems, i.e., in river Ganges at Fatehpur and Allahabad, as well as in river Yamuna at Allahabad, and molecular heterogeneity among these worms have been extensively investigated. The pathways of transmission of non native alien species due to long distance migratory habits of Rita rita, man-made alterations including dredging in long stretches of the river bed of Ganges to facilitate ballast water transfer mechanism owing to the commercial ship movements between Haldia and Allahabad; and sudden water chemistry (salinity, hardness, alkalinity) alteration (due particularly to rainy period) oriented micro-fauna interchange are identified, and remedial measures suggested. PMID- 27413304 TI - Comparative efficacy of pour-on eprinomectin and ivermectin against Sarcoptes scabiei in buffaloes. AB - The efficacy of eprinomectin and ivermectin pour-on was evaluated against Sarcoptes scabiei in naturally infested buffaloes. Eighteen animals were allocated into three groups (A, B and C) of six animals each. Animals in group A were treated with eprinomectin (pour-on) @ 0.5 mg/kg; group B with ivermectin (pour-on) @ 0.2 mg/kg while group C served as untreated controls. Skin scrapings were examined on days 0, 7, 14, 21, 28 and 42 post-treatment (PT). Skin scrapings were found free for mites on day 21 PT, with marked clinical improvement in the lesions after day 28 of treatment. Untreated control group continued to show severe progressive lesions throughout the study period. No clinical side-effects of the tested drugs were observed after treatment. This preliminary report on the efficacy of eprinomectin (pour-on) against S. scabiei in buffaloes is encouraging and results could be of considerable importance. PMID- 27413305 TI - In vitro and in vivo anthelmintic activity of Murraya koenigii against gastro intestinal nematodes of sheep. AB - The present study have been conducted to evaluate the anthelmintic activity of crude aqueous and crude methanolic leaf extracts of Murraya koenigii. Infection of ruminants with gastro-intestinal (GI) parasite has become a worldwide problem. The parasite causes economic losses in a variety of ways. Previously sheep producers relied heavily on anti-parasitic drugs to control gastro-intestinal parasites of the flocks. But due to misuse of these drugs the parasites become resistant to drugs. Thus created interest in studying medicinal plants as an alternative source of controlling the GI parasites. Adult motility assay (AMA) and egg hatch assay (EHA) have been done for in vitro study, and faecal egg count reduction (FECR) assay have been done for in vivo study. The in vitro study revealed anthelmintic effects of M. koenigii on Haemonchus contortus as evident from their paralytic condition and/or death at eight hour post exposure in different concentrations (12.5, 25, 50 mg/ml) of aqueous and methanolic extracts which exhibit to be dose-dependent. Aqueous and methanolic extracts of M. koenigii were found to have low percent inhibitory effect on egg hatching. It may be concluded that M. koenigii showed significant anthelmintic activity. PMID- 27413306 TI - Viability and morphological changes of Acanthamoeba spp. cysts after treatment with Effective microorganisms (EM). AB - Acanthamoeba is a free-living opportunistic protozoan parasite that is found in diverse environments. It can cause keratitis, mostly related to inappropriate use of contact lenses, as well as life threatening diseases including encephalitis, disseminated sinusitis, and skin ulcers. This study investigated morphological changes and fine structures of the cyst form of Acanthamoeba spp. after treatment with effective microorganisms (EMTM) using light and scanning electron microscopies. Acanthamoeba cysts treated with 1:2, 1:4, 1:6, and undiluted EMTM showed higher percentages of non-viable cysts than those treated with 1:8, 1:10, 1:100, 1:200, and 1:400 EMTM and at 5 days post-treatment developed from cystic stage to trophozoite stage. Acanthamoeba cysts treated at concentrations of 1:2, 1:4, 1:6, and undiluted EMTM exhibited cytoplasmic clumping and shrinkage of amoeba cells away from cyst walls. The effective EMTM concentration lethal to Acanthamoeba spp. cyst could provide information to monitor the environmental control system. PMID- 27413307 TI - In vitro bionomics of an ischnoceran louse, Lipeurus caponis (Phthiraptera: insecta). AB - Poultry wing louse, Lipeurus caponis was reared in vitro condition (35 +/- 1 degrees C, 75-82 % RH) to record the incubation period of the eggs, duration of nymphal instars, adult longevity and the egg rate. The data obtained through in vitro studies was utilized to construct the life table and to determine the intrinsic rate of natural increase. The value of rm of L. caponis appeared to 0.046. At this rate, the population of lice is supposed to double after 16.1 days, indicating it to be a moderate breeder. PMID- 27413308 TI - Abattoir survey of abamossal nematodes of sheep in Srinagar district (J & K). AB - Gastrointestinal trichostrongyles of small ruminants are one of the major causes of productivity loss. Epidemiological study was carried out to determine parasitic infection of sheep with abamossal nematodes at various abattoirs in Srinagar district of Kashmir Valley from August 2011 to July 2012. On the basis of necroscopy, out of representative 281 abamossa, 53.3 % were recorded to be infected with Haemonchus species and 41.2 % with Ostertagia spp. Thus, Haemonchus spp. were more prevalent than Ostertagia spp. in ovines (P > 0.05). Infection prevalence percentage of Haemonchus spp. was highest in late summer season and early rainy season (62.85 %) with peak value in the month of July (71.42 %) and lowest in winter (42.85 %) with minimum value in the month of February (40 %). Similar trend was seen with Ostertagia spp. having highest infection prevalence value during summer season (52.8 %) with peak values in the month of July (64.2 %) and lowest infection in winter (34.2 %) with minimum value in February (30 %). Moreover, non-local breeds were more prevalent than local ones (P = 0.05). PMID- 27413309 TI - Seroepidemiological study of toxoplasmosis in southern districts of Tamil Nadu. AB - The current study was conducted with the objectives of estimating the seroprevalence of Toxoplasma gondii and associated socio-demographic, clinical and behavioural characteristics in and around Tirunelveli. Serum samples from 175 immunodeficient and 175 immunocompetent patients were collected and were analyzed by in-house enzyme linked immunosorbent assay (ELISA). A questionnaire survey was administered for all study participants to gather information on risk factors. The present study revealed that anti- T. gondii IgG antibodies were detected in 13.14 % which constitutes 15.43 % in immunocompromised and 10.86 % in immunocompetent patients. There was a significant difference between sex of the study population and drinking water source. Seroprevalence was increased in the male (19.12 %, p = 0.0075, OR 2.316, 95 % CI 1.2362-4.3405) than the female and with river water consumption other than bore water (12.5 %, p = 0.0483, OR 0.857, 95 % CI 0.1853-3.4641). No significant relations were observed between anti Toxoplasma IgG antibodies and age, residence, diet and animal contact in the study population. Toxoplasmosis will remain a problem, mainly in risk groups such as pregnant women and immunocompromised patients. Improvement can only be attained by increasing prevention and reducing the risk factors. PMID- 27413310 TI - The role of climate on prevalence or eradication of vesical schistosomiasis in Khuzestan Province of Iran. AB - Climate is defined as the combination of climate and air elements of a given region which is usually measured for a period of decades. De-marton climate classification has been established based on many factors, including elements such as temperature and rainfall. Vesicle schistosomiasis is a parasitic disease caused by Schistosoma haematobium. This parasite lives in the blood vessels of the bladder. The parasite can cause hematuria in human and if not treated properly can lead to vesicale carcinoma. The parasite is distributed only in certain parts of the province and it is highly dispersed along the rivers of Dez, Karkheh and Karun with high emissions. In 1970, the prevalence of infection in infected foci was 23.8 %. Campaign against the parasite began in 1958 but it did not encompass all centers of infection. Preventive measures include diagnosis and treatment of patients, public health promotion, health education, drying swamps and ponds, improving the environment, cementing the irrigation canals, and the use of moluscocide eventually leads to changing the ecological and conditions of parasite and snail inhabits. Application of preventive measures resulted in the reduction of infection level to 0.7 % in 1979. By continuing struggle and intensifying preventive measures and changing ecological and climatic environment, in 2008, the examination of 3400 urine samples of students in Andimeshk district revealed no cases of the vesical schistosomiasis. It is concluded that S. haematobium and vesical schistosomiasis is eliminated from Khuzestan province southwest Iran, but the disease is still prevalent in neighboring Iran's western border country (Iraq) and due to the special conditions of its facilities and the traffic between the two countries, it is necessary to control and eradicate the disease in Iraq by using the experiences of Iran in eliminating the disease. PMID- 27413311 TI - Effect of bee venom or proplis on molecular and parasitological aspects of Schistosoma mansoni infected mice. AB - The present study was performed to elucidate the efficacy of Apis mellifera L bee venom (BV) or proplis (200 mg/kg orally for three consecutive days) on Schistosoma mansoni infected mice. The results recorded reduction in the total worm burden, numbers of immature eggs and the ova count in hepatic tissue in BV (sting or injection) or proplis treated groups as compared to the infected group. Histological examination illustrated a significant increase (P <= 0.05) in the diameter of hepatic granuloma in BV treated groups (272.78 and 266.9, respectively) and a significant decrease in proplis treated mice (229.35) compared with the infected group (260.67). Electrophoretic pattern of RNA showed a decrease in mean of maximal optical density in liver and intestine of S. mansoni infected mice treated with bee venom (sting or injection) as compared with infected group. Flow cytometry analyses of RNA or apoptotic percentage of worms recovered from BV sting (19 and 49 % respectively); BV injected (20.5 and 51.17 %, respectively) and proplis (35 and 23.93 %, respectively) groups were compared with S. mansoni infected group (37.87 and 39.21 %, respectively). It can be concluded that administration of bee venom or proplis are effective in case of S. mansoni infection. Although bee venom cause increase of granuloma diameter and this might be due to venom concentration and further studies are required to avoid such harmful effect. PMID- 27413312 TI - Anticoccidial effects of herbal extracts on Eimeria tenella infection in broiler chickens: in vitro and in vivo study. AB - Safe alternative anticoccidial drug to chemical feed additives are herbal extracts, because they don't results to tissue residue and drug resistance. In order to evaluate the effects of herbal extracts to control avian coccidiosis, 180 one-day-old broiler chickens were randomly divided into nine equal groups, as follows: (1) Biarum bovei (2) Nectaroscordum tripedale( 3) Dorema aucheri (4) Cichorium intybus (5) Prangos ferulaceae (6) diclazuril (7) Artemisia absinthium (8) infected control (9) uninfected control (each contains two groups). Administration of herbal extracts and supplementation of diclazuril was began 2 days before challenge and lasted for the duration of the experiment. The chicks of all the groups except uninfected control group were inoculated orally with sporulated oocysts (3 * 10(3) oocysts of Eimeria tenella) on the day 22 of age. The criteria employed were: body weight, feed conversion ratio, blood in feces, survival rate, lesion scoring, number of oocyst output per gram feces and histopathological changes. For histopathological evaluation, on day 12 post inoculation three birds from each group were randomly selected and humanly sacrificed. N. tripedale and diclazuril revealed better results in terms of growth performance, lesion score, extent of bloody diarrhea and oocyst count as compared to other herbal extracts. The increase in the severity of lesions was observed in groups of D. aucheri, A. absinthium, B. bovei, P. ferulaceae, C. intybus, diclazuril and N. tripedale, respectively. In conclusion, the current study showed that herbal extracts were effective in control of coccidiosis caused by the E. tenella infection. PMID- 27413313 TI - Anticoccidial activity of aqueous extract of a wild mushroom (Ganoderma applanatum) during experimentally induced coccidial infection in broiler chicken. AB - Despite presence of anticoccidial drugs and vaccines in the market, coccidiosis continues to result in substantial economic losses to the poultry industry. There is wide-spread resistance to already known anticoccidial drugs. It is an infectious disease of poultry and rigorous management is required during vaccination. In addition there is possibility of drug residues in meat and other byproducts of such treated animals and consequently makes more imperative to explore and understand the role of natural products in livestock parasite management. Therefore a study was designed to evaluate the anticoccidial activity of aqueous extract of Ganoderma applanatum in broiler chicken. In-vivo anticoccidial activity of aqueous extract of G. applanatum was measured in comparison to the reference drug amprolium on the basis of oocysts per gram of faeces, weight gain and feed conversion ratio. Oocyst output was measured with the help of Mc-Masters counting technique. The results of this study established the virulence of coccidian oocysts and the effectiveness of both amprolium and aqueous extract of G. applanatum against coccidian oocysts, confirmed by the fact that treatment with aqueous extract of G. applanatum resulted in a noticeable reduction in coccidian oocysts output, leading to improved weight gain and better feed conversion ratio. The study highlighted the potential of G. applanatum as a natural source of bioactive components for controlling a protozoan parasite, which can be isolated and tested in a bioassay-guided manner and harnessed in the form of anticoccidial drugs. PMID- 27413314 TI - Comparison between the effect of Lawsonia inermis and flubendazole on Strongyloides species using scanning electron microscopy. AB - Strongyloides species is a helminth of worldwide distribution primarily in tropical and subtropical regions. It is the only soil-transmitted helminth with the ability for autoinfection so; it may lead to severe systemic manifestations especially in immunosuppressed patients. Chemotherapy is currently considered the best therapeutic option for strongyloidiasis but some drugs are expensive and others have side effects as nausea, diarrhea and headache. Strongyloides larva is resistant to most chemical agents so, search for plant extracts may provide other effective but less expensive treatment. Lawsonia inermis Linn, popularly known as Henna, has been proven to have antihelminthic, antibacterial and antifungal properties. The current study was carried out to evaluate the efficacy of Lawsonia inermis on Strongyloides spp. In vitro using scanning electron microscopy. Fifty Strongyloides species. larvae and free living females were incubated with different concentrations of Lawsonia (1, 10, 100 mg/ml), for different incubation periods (24, 48, 72 and 96 h) in comparison to the same concentrations of flubendazole at the same different time points. The results showed that Lawsonia inermis in a concentration of 10 mg/ml incubated with Strongyloides spp. female for 24 h affected the parasite cuticular surface in the form of transverse and longitudinal fissures and transverse depression in comparison to no cuticular change with flubendazole (100 mg/ml). This suggests that Lawsonia inermis may be a promising phytotherapeutic agent for strongyloidiasis. PMID- 27413315 TI - Evaluation of the antileishmanial and cytotoxic effects of various extracts of garlic (Allium sativum) on Leishmania tropica. AB - Cutaneous leishmaniasis (CL) is a major public health problem in tropical and subtropical countries worldwide. Treatment of CL by pentavalent antimony compounds remains a challenge because of limited efficacy, toxic side effects and drug resistance. In the present study, in vitro antileishmanial and cytotoxic activity of garlic extracts against promastigote forms of Leishmania tropica and murine macrophages was evaluated by colorimetric cell viability (MTT) assay. The results revealed that the methanolic and aqueous extracts of garlic were effective in inhibiting promastigote growth of L. tropica with IC50 (50 % inhibitory concentrations) values 12.3 and 19.2 ug/ml, respectively. In addition, methanolic and aqueous extracts of garlic showed low cytotoxicity against murine macrophages with CC50 (cytotoxicity concentration for 50 % of cells) values 291.4 and 348.2 ug/ml, respectively. Findings of present study were the first step in the search for new antileishmanial drugs. However, further works are required to evaluate exact effect of these extracts in volunteer human subjects. PMID- 27413316 TI - Immune responses in DNA vaccine formulated with PMMA following immunization and after challenge with Leishmania major. AB - Leishmaniasis is a major infectious disease caused by protozoan parasites of the genus Leishmania. Despite of many efforts toward vaccine against Leishmania no effective vaccine has been approved yet. DNA vaccines can generate more powerful and broad immune responses than conventional vaccines. In order to increase immunity, the DNA vaccine has been supplemented with adjuvant. In this study a new nano-vaccine containing TSA recombinant plasmid and poly(methylmethacrylate) nanoparticles (act as adjuvant) was designed and its immunogenicity tested on BALB/c mouse. After three intramuscular injection of nano-vaccine (100 MUg), the recombinant TSA protein (20 MUg) was injected subcutaneously. Finally as a challenge animals were infected by Leishmania major. After the last injection of nano-vaccine, after protein booster injection, and also after challenge, cellular immune and antibody responses were evaluated by ELISA method. The findings of this study showed the new nano-vaccine was capable of induction both cytokines secretion and specific antibody responses, but predominant Th1 immune response characterized by IFN-gamma production compared to control groups. Moreover, results revealed that nano-vaccine was effective in reducing parasite burden in the spleen of Leishmania major-infected BALB/c mice. Base on results, current candidate vaccine has potency for further studies. PMID- 27413317 TI - Evaluation of s.c. route of immunization by homologous radio attenuated live vaccine in experimental murine model of visceral leishmaniasis. AB - Our previous studies in BALB/c mice showed substantial protection against the experimental murine visceral leishmaniasis (MVL) when the animals were immunized with gamma-irradiated live Leishmania donovani parasites through intra peritoneal (i.p.) and intra muscular (i.m.) routes respectively. The observations encouraged us to check the prophylactic efficacy of subcutaneous (s.c.) route as it is better alternative for human trial. The mice immunized with two subsequent doses of the radio attenuated homologous vaccine were challenged with virulent L. donovani parasites. Seventy-five days post infection, the animals were sacrificed. The extent of protection against the disease was evaluated by assessing the reduction of parasite burden in spleen and liver, the generation of free radicals (NO & ROS) and release of the cytokines from T-lymphocyte helper 1 (Th 1) and T-lymphocyte helper 2 (Th 2) along with the measurement of the serum immunoglobulins. The reductions in parasitic burden were observed up to 21 and 24 % in spleen and liver of the immunized groups with NO and ROS productions 27 and 34 % respectively. Whereas the increase in IFN gamma releases was between 19 and 34 %, the decrease in IL-10 release was not more than 22 %. This indicates the failure of the establishment of pronounced Th1 ambience which was further corroborated by the observed IgG2a and IgG1 ratio. The present study when compared with our previous observations with i.m. and i.p. routes revealed that s.c. route may not be a good choice for the use of radio attenuated vaccine. PMID- 27413318 TI - Survey of hydatidosis infection in slaughtered camel (Camelus dromedarius) in Tabriz area, Northwest Iran. AB - Hydatid Disease is the name given to the condition caused by the zoonotic tapeworm Echinococcus granulosus. The tapeworm spends most of its adult life in the intestine of its definitive host, namely canids and in particular the dog. The tapeworm eggs become voided in the canids' faeces and as a result of ingesting the eggs, infection passes to the intermediate host, commonly herbivores while grazing. However, humans can become accidentally infected and hydatid cysts may develop throughout the body. During April 2010-February 2014, a total 198 camels, which had been sent to the abattoir, the daily number of hydatid infected livers and lungs of camels slaughtered at Tabriz abattoir were recorded. To be sure about the validity of recorded data, observed data were collected daily. Approximately 29 (14.64 %) of camels were infected according to this survey. Age wise, the prevalence of infection in young animals (under the age of 5 years) was 4 (2.02 %), whereas in animals between 5 and 10 years and over, the prevalence of infection was 11 (5.55 %) and 14 (7.07 %) respectively. Sex wise, female animals had a higher prevalence with 17 (19.76 %) cases in camels, whereas in the males, there were 12 (10.71 %) cases in camels. There was a notable difference found in our study between male and female animals (P < 0.05). Infections were recorded in two visceral organs with the Lungs having the highest prevalence in camels, and the liver had low infected in camels. The results of this study suggest that infection of camels with hydatid cyst is common in Tabriz, Iran and that this may constitute economic and health problems in the meat industry. PMID- 27413319 TI - Prevalence of ectoparasites in free-range backyard chickens, domestic pigeons (Columba livia domestica) and turkeys of Kermanshah province, west of Iran. AB - This study was carried out on free-range backyard chickens, domestic pigeons (Columba livia domestica) and turkeys from May 2012 to April 2013 to determine the prevalence and identify the species of ectoparasites in Kermanshah province, west of Iran. Of the total of 600 free-range backyard chickens (185 ? and 415 ?), 700 domestic pigeons (278 ? and 422 ?) and 150 turkeys (53 ? and 97 ?), 389 (64.83 %), 608 (86.85 %) and 54 (36 %) were infected with one or more parasites respectively. Eleven ectoparasites species including five of lice (50.16 % Menacanthus stramineus, 13.66 % Menopon gallinae, 4.83 % Cuclotogaster heterographus, 5.16 % Goniocotes gallinae, 2.33 % Goniodes gigas), three of mites (26.33 % Dermanyssus gallinae, 8.5 % Ornithonyssus bursa, 7 % Cnemidocoptes mutans), one of tick (78.66 % Argas persicus) and two of flea (12.33 % Echidnophaga gallinacea, 2 % Pulex irritans) were found in the backyard chickens. The domestic pigeons were infected with six species of parasites including: Columbicola columbae (61.7 %), M. gallinae (10.43 %), M. stramineus (9 %), D. gallinae (8.28 %), Argas reflexus (74.14 %) and Pseudolynchia canariensis (27.7 %). The ectoparasites species recorded in turkeys were M. gallinae (14 %), M. stramineus (8 %), D. gallinae (12.66 %), C. mutans (6 %), A. persicus (24.66 %) and E. gallinacean (6 %). This is the first survey to determine the prevalence and identify the species of ectoparasites among free-range backyard chicken, domestic pigeons and turkeys in Kermanshah province. The high prevalence rate of ectoparasites in free-range backyard chickens and domestic pigeons indicates that parasitic infection is a common problem in this area. PMID- 27413320 TI - Prevalence of ectoparasites in owned dogs in Kerman city, southeast of Iran. AB - The present study aimed to investigate the intensity and distribution of natural infestation of ectoparasites in owned dogs during June to November 2011 in Kerman city, southeast of Iran. One hundred two domestic dogs (63 males, 39 females) with age ranged between 45 days to 13 years were examined for ectoparasites infestation including (tick, lice, flea and mite) in Kerman city. Detailed questionnaire about grooming and bathing interval, keeping place (outdoor, indoor) and purpose of keeping were obtained from owners. After complete skin examination, animals hairs were combed and their skin rubbed with a piece of cotton soaked in alcohol to remove the ectoparasites in apparently normal cases, and deep skin scratching were prepared from all type of lesions in symptomatic dogs. A total number of 149 ectoparasites were collected. The most common ectoparasite was Rhipicephalus sanguineus tick, which infested 27 of the 102 dogs (26.47 %). Ctenocephalides canis was identified on two dogs (1.96 %) and 5 dogs infested with Hippobosca spp (4.9 %) that the highest infestation rate was seen in September (14.2 %). Studied samples were routinely checked for clinical symptoms. Itching and scratching lesions were the only reported signs which seen in flea infested dogs (6.4 %) and other infested dogs (93.5 %) had no clinical symptoms. Ectoparasites were significantly higher in outdoor dogs in compare with indoor group and the most tick infested location was ear (61.3 %) (P < 0.05). PMID- 27413321 TI - A retrospective survey of hydatidosis based on abattoir data in Kermanshah, Iran from 2008 to 2013. AB - A retrospective study was carried out from 2008 to 2013 to estimate the prevalence of hydatidosis in ruminants slaughtered at the Kermanshah municipal abattoir, in western Iran. A total number of 663,633 livestock (393,585 sheep, 81,080 goats and 188,968 cattle) slaughtered in the 5-year period and overall 9,524 (1.43 %) livers and 13,147 (1.98 %) lungs were condemned. The lungs were more frequently infected with hydatid cysts than the livers in all animal species. The average prevalence of hydatidosis was 2.7 % in this area. The prevalence of Echinococcus granulosus infection recorded in the present study was generally lower than those reported from other regions of Iran. Greater awareness among farmers, destruction of organs containing hydatid cysts, prevention of access of dogs to raw offals and implementation of national rabies control program could be responsible factors. The results showed a significant difference (p < 0.001) in the prevalence of hydatidosis among studied animals with higher prevalence in cattle than sheep, with the lowest prevalence recorded in goats. However the annual prevalence of liver and lung condemnations due to hydatidosis was decreased in some years, but the overall trend had a variable pattern in the prevalence of hydatidosis over the study period. Data showed a significant seasonal pattern for hydatidosis in all studied animals. Liver and lung condemnations due to hydatidosis were higher in the fall for sheep and cattle, whereas in goats were higher in summer. This could be attributed to various factors such as sources of slaughtered animals, changes in management practice and ecological factors. The current results suggest that a systematic investigation that lead to a disease control strategy is required to reduce the economic and public health consequences of hydatidosis. In addition, the present survey provides baseline data for the future monitoring of this potentially important parasitic disease in the region. PMID- 27413322 TI - Sero-prevalence of Haemonchus contortus infection in sheep by Indirect-ELISA using somatic antigen. AB - The present work was carried out to study the sero-prevalence of Haemonchus contortus infection in sheep by Indirect-Enzyme Linked Immuno Sorbent Assay (Indirect-ELISA) using somatic antigen. Out of 100 abomasums screened, 57 found positive for H. contortus adult worms. A total of 250 serum samples which includes, 100 serum samples from local abattoir in and around shimoga region from the animals from which the abomasums were collected and 150 serum samples from migratory sheep were used to detect the circulating antibody against H. contortus by Indirect-ELISA using somatic antigen. Of the 57 sheep harboring adult worms in their abomasums, the serum samples showed positive reaction by Indirect-ELISA with somatic antigen. However, among 43 sheep which are not showing any adult worms of H. contortus in their abomasums, but their 21 serum samples showed positive reaction by Indirect-ELISA. The sensitivity and specificity of Indirect ELISA was found to be 100 and 67.18 %, respectively. Also, the sero-prevalence of H. contortus infection was found to be 58.66 % out of 150 migratory sheep serum samples screened for detecting circulating antibodies of H. contortus by Indirect ELISA using somatic antigen in and around shimoga region. PMID- 27413323 TI - Epizootological study of small ruminant gastrointestinal strongyles in Gamo-Gofa Zone, Southern Ethiopia. AB - The study was conducted with the objective to estimate the prevalence of gastrointestinal strongyles and identifying the prevailing strongyle species Gamo Gofa Zone. A total of 598 animals (241 sheep and 357 goats) and 45 animals (20 sheep and 25 goats) were examined coproscopically and by post mortem, respectively. The overall coproscopic prevalence of strongylosis in the study area was 51.4 %. Strongyles were more prevalent in sheep than goats (95 % CI is 74.6-84.8 % and 58.6-68.6 % for sheep and goats, respectively; P < 0.05). A higher prevalence (P < 0.05) of strongyles infection was recorded in the midland and highland than the lowland, and in wet season than the dry season. The mean fecal egg count was found to be significantly higher (P < 0.05) in the midland area (908.7 +/- 94.5) and in wet season (1,033.7 +/- 84.2). The post mortem examination result indicated that the overall prevalence of gastrointestinal strongyles was 97.7 %; and a total of 11 strongyle species were identified of which Trichostrongylus axei, Teladorsagia species, Trichostrongylus colubriformis and Haemonchus contortus were the dominant and with higher load. During this study infection with multiple parasites, 3 and more 3, species were recorded in about 68 % goats and 85 % sheep. This study revealed the very high strongyle prevalence and higher proportion of multiple parasitism both in sheep and goats. Hence, it suggests the need to the institution of various control measures like strategic anthelmintic treatment for efficient utilization of the available small ruminant resources. PMID- 27413325 TI - Prevalence of Toxoplasma gondii in Chicken samples from delta of Egypt using ELISA, histopathology and immunohistochemistry. AB - Estimates of the zoonotic diseases are helpful for monitoring and improving public health. Laboratory-based surveillance provides crucial information for assessing zoonotic disease trends and developments. Toxoplasmosis is considered as a zoonotic disease and has both medical and veterinary importance since it leads to abortion in humans and several animal species. In view of the worldwide importance of T. gondii, this study aimed to estimate the prevalence of T. gondii in chickens from the Delta of Egypt. A total of 304 blood and brain samples were collected from Egyptian chickens from Gharbiya, Qalyoubiya, Minufiya, Beheira, Kafr EL-Shaykh and Dakahlia Provinces. In order to determine the serological and histopathological prevalence of T. gondii, the samples were examined by ELISA, histopathology and immunohistochemistry (IHC). The prevalence of T. gondii was 11.18, 6.91, 6.91 % by ELISA, histopathology and IHC, respectively. Statistically significant differences in the prevalence of T. gondii were observed on the basis of season, sex and habitat. These data provide valuable information regarding the epidemiology of T. gondii infections in Egyptian chickens, which can be employed in developing efficient strategies for disease management and control. PMID- 27413326 TI - Haemato-biochemical and thyroxin status in Trypanosoma evansi infected dogs. AB - In one year period of study, dogs with inappetence, fever, ocular discharges, dullness, enlarged lymph nodes were screened for the presence of haemoprotozoans at College Hospital of College of Veterinary Science, Tirupati. Wet blood film examination and stained blood smear examination was done to confirm the condition. Peripheral blood smears of dogs revealed the presence of Trypansomes. Trypanosoma evansi was confirmed based on the morphology and measurements of the organisms in the stained blood smears. Haematology revealed decreased total erythrocyte count, packed cell volume, haemoglobin and total leucocyte count values. Total serum proteins, albumin and glucose levels were decreased significantly (P < 0.01), but a significant increase (P < 0.01) in cholesterol, blood urea nitrogen, serum alkaline phosphatase, serum aspartate aminotransferase and serum alanine aminotransferase levels were observed. Decreased total T4 and free T4 were also observed in the T. evansi infected dogs. PMID- 27413324 TI - Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis. AB - Leishmaniasis is one of the neglected infectious diseases included in the World Health Organization's list of the top guns of antimicrobial resistance. Miltefosine is the first and the only available oral effective therapy for leishmaniasis. For fear of its potential resistance, identification of alternative, effective and safe drugs is urgently needed. Therefore, in view of azithromycin promising activity against a number of Leishmania species, this work was carried out to evaluate the efficacy of oral azithromycin alone versus its combination with miltefosine against experimental Old World Cutaneous leishmaniasis thus, can provide another alternative oral therapy or for the first time an oral combination therapy for leishmaniasis. The experiment were carried out on Swiss strain albino mice which were treated either with miltefosine for 20 days, Azithromycin for 20 days or both drugs in combination therapy for shorter duration of 10 days. Efficacy of azithromycin mono and combination therapy with miltefosine was evaluated clinically, parasitologically and by examination of the cutaneous lesions by Transmission Electron Microscopy. The current work demonstrated superior activity of oral azithromycin over oral miltefosine in the treatment of experimentally infected mice with Leishmania major (MHOM/IL/81/FEBNI). Unfortunately, oral combination therapy of azithromycin and miltefosine for short duration though, induced dramatic clinical improvement yet, relapse rapidly developed after cessation of therapy. Oral azithromycin could be a promising oral antileishmanial agent. Further research is recommended to investigate its leishmanicidal activity against other Leishmania species thus; another alternative oral therapy for leishmaniasis can be rapidly available. PMID- 27413328 TI - Survey of Lernaeid in Shizothorax zarudnyi from Chahnimeh lakes in Sistan, Iran. AB - The Lernaeid parasites, Lernaea spp, are crustacean ectoparasites that occur in a variety of fishes worldwide. In the present study, Shizothorax zarudnyi (n = 1,500) were examined during August 2012 to 2013 to determine the prevalence of Lernaeid parasites at one Species fish of Chahnimeh lakes Sistan, Iran. Two species of the genus Lernaea; L. cyprinacea and L. polymorpha, were recorded. The overall prevalence rates of L. cyprinacea and L. polymorpha were 15.47 and 10.20 % respectively. The relationship between body weight and Lernaeid parasites showed that prevalence of L. cyprinacea and L. polymorpha was highest in weight group of 250-400 g and lowest in weight group of 500-700 g. The overall percentage of infestations in study was the highest (42.5 %) in summer, moderate (33.6 %) in spring and the lowest (17.25 and 6.62 %) in the autumn and winter season, respectively. The number of detected Lernaeid parasites and infested fish were 6,140 and 800 respectively. The mean intensity of infestation was 7.68. There was significant correlation between parasite prevalence and intensity with host weight (P = 0.000). Knowledge of the prevalence of Lernaeid parasites and current Lernaea species will help to minimize the economic losses in the fish industry, evaluate infestation potential and control programs, especially for other fishes. PMID- 27413327 TI - Geohelminths distribution as affected by soil properties, physicochemical factors and climate in Sharkyia governorate Egypt. AB - Soil-transmitted helminths are mainly a group of parasitic nematodes causing human infection through contact with parasite eggs or larvae; they survive in the warm and moist soil of the tropical and subtropical countries. This study was carried out in Sharkyia governorate from October, 2011 to October, 2013, to correlate between the prevalence and distribution of these parasites in the soil and the physicochemical factors affecting the examined samples of the soil. One hundred and twenty samples of different types of soil (clay, silt, sand) from different localities were collected and examined. Diagnosis of geohelminths was confirmed by the recovery of their eggs and larvae with other protozoa by different parasitological methods. The modified baermann method was found to be more efficient in detection of geohelminths larvae than charcoal culture method. Among the examined sites geohelminths were much more numerous in the soil of rural areas especially in the spring and summer seasons, while the contamination of canal banks by geohelminths was the worst (80 %). An insignificant correlation was reported between the soil texture and the number of positive samples in the examined areas while the relationship was directly proportional among (moisture, PH, organic). It appeared that the most common geohelminthic stage was Toxocara spp. eggs besides other types of protozoa especially Balantidium coli cysts. This suggests that factors other than soil texture are important in the prevalence of geohelminths in the soil e.g. temperature, moisture, PH and organic matter. So, to change some of these factors in a trial to control geoparasites transmission but with keeping the environment should be tried. These results also open the way to further studies to highlight the mutual affection between inhabitants of these sites and the prevalence of these geoparasites. PMID- 27413329 TI - Seroprevalence of canine leishmaniasis in Kwara, Oyo and Ogun states of Nigeria. AB - Leishmaniasis is an important tropical disease that is gradually gaining attention in Nigeria. The canine species which include domestic dogs have been named the reservoir host for the zoonotic form of leishmaniasis. The present study was carried out to determine the seroprevalence of canine leishmaniasis in three selected states of Nigeria using indirect enzyme linked immunosorbent assay (ELISA). Two hundred and seventy-three canine sera were tested for Leishmania IgG antibodies. Dogs sampled were grouped into young (<1 year) and adult (>1 year). Total prevalence recorded was 4.40 % (12/273). There was no significant difference (P > 0.05) between sera of hunting (4.83 %) and companion dogs (3.03 %). Furthermore, there was no significant difference (P > 0.05) between young and adults dogs. There was no correlation between sex and prevalence of canine leishmaniasis. However, significant difference (P < 0.05) was observed in the prevalence of each state with Kwara, Oyo and Ogun having 14.63, 3.33 and 1.32 % respectively. The result of this study established the presence of canine leishmaniasis in Oyo, Ogun and Kwara States of Nigeria making the zoonotic form of the disease a possibility. PMID- 27413331 TI - Prevalence of toxoplasmosis and related risk factors among humans referred to main laboratories of Urmia city, North West of Iran, 2013. AB - Toxoplasmosis is mostly asymptomatic infection in immunocompetent individuals while it can cause a severe infection in human fetus during pregnancy and immunocompromised patients. This study aimed to determine the prevalence of anti Toxoplasma IgM and IgG seropositivity and potential risk factors of the infection in humans referred to Urmia City main diagnostic laboratories, Urmia, Iran. Totally 195 blood samples were collected from the individuals referred to main diagnostic laboratories of Urmia City, 2013. Serum concentration of anti Toxoplasma IgG and IgM were determined using ELISA method. Demographic variables of the participants were collected by interviewing, which are including sex, age, occupation, educational and residential status, eating undercooked meat, consumption of raw vegetable and the method of washing raw vegetables. None of all 200 serum sample were anti-Toxoplasma IgM positive, but different concentrations of anti-Toxoplasma IgG were observed in 88 (45.12 %) of samples. The significant higher rate of anti-Toxoplasma IgG seropositivity were observed in people with soil related jobs (P = 0.005, OR = 2.266; 95 % CI 1.260, 4.078) and history of eating raw vegetables at restaurant (P = 0.036, OR = 1.985; 95 % CI 0.991, 3.978). Also anti-Toxoplasma IgG concentration mean was significantly higher in people who were commonly eaten raw vegetable at restaurants (P < 0.001, t = 7.918). The prevalence of chronic toxoplasmosis is considerably high while the acute infection is very low in the studied area. Having soil related jobs and eating raw vegetables at restaurants increases the risk of acquiring the infection. PMID- 27413330 TI - Serological study of Toxoplasma gondii infection in Turkoman horses in the North Khorasan Province, Iran. AB - Toxoplasmosis is an important zoonotic disease with worldwide distribution. The infection is observed in an unusually wide range of warm-blooded animals, including most of the livestock and humans. Many studies have shown high prevalence of toxoplasmosis in man and animals in Iran. The present study was conducted to investigate the seroprevalence of toxoplasmosis in Turkoman horses in the North Khorasan Province. During 2011-2012, 100 blood samples from horses were collected and tested for antibodies against toxoplasmosis using indirect fluorescent antibody test. The seroprevalence of toxoplasmosis was detected in 14 % (14) horses. The antibodies titres were detected in the range of 1:20-1:160 dilution. The lowest and highest frequencies of toxoplasmosis were observed in the age groups of <1 year and 1-10 years, respectively (P < 0.05). No significant difference was observed between toxoplasmosis frequencies and gender and usage of horses. With regard to the high frequency of toxoplasmosis in the sampled horses, attention must be paid to the animal health for the control and prophylaxis of the disease. PMID- 27413332 TI - A report on the incidence of Trichodina heterodentata from fishes of Jammu, J&K India. AB - The present study was aimed at screening for the presence of protozoan's among Cyprinid fishes collected from various fish ponds and farms in Jammu division of Jammu and Kashmir (J and K) state. Out of 75 fishes collected from local water bodies of Jammu division, only 35, (49.6 %) were infested with Trichodina. Trichodina infestations were studied in the period from November to February. In light infestation Trichodina was usually present on gills, fins and skin of apparently healthy fish. Clinical signs of Trichodiniasis appeared on fish with heavy infections and in presence of one or more stress factors including, rough handling during transportation from ponds, over crowdedness, malnutrition, high concentration of free ammonia and low oxygen concentration. Clinical signs of Trichodiniasis in fish such as sluggish movement, loss of appetite, black colouration, necrosis and ulcer on different parts of the body, detached scales and excessive accumulation of mucous in gill pouches were also observed. PMID- 27413333 TI - Anthelmintic efficacy of aqueous extract of Zanthoxylum armatum DC. seeds against Haemonchus contortus of small ruminants. AB - Haemonchus contortus infection is the major hurdle in growth and productivity in small ruminants especially in tropical countries. Indiscriminate and long term use of currently available chemotherapeutic agents lead to development of resistance in microorganisms and residual problems in population. Therefore, present study was undertaken to evaluate the anthelmintic efficacy of aqueous extract of Zanthoxylum armatum DC. seeds against adult H. contortus worms of small ruminants. Proximate analysis of seed powder shows high crude protein, Cu, Zn and Ca concentration. Phytochemical ingredients of extract revealed high total phenolic, flavonoids and tannin contents. In vitro experimental trial revealed complete mortality of H. contortus worms at the concentration of 100 mg/ml at the time exposure of 8 h. At 50 mg/ml concentration the mortality at 6 and 8 h were 45.45 +/- 4.55 and 63.64 +/- 4.54 %. Median lethal concentration (LC50) at 6 and 8 h were 59.90 and 28.92 mg/ml, respectively. Levamisole at concentration of 0.5 mg/ml caused 50 % mortality at 2 h post exposure and 100 % mortality at 4 h post exposure. The results confirm the cidal effect of the aqueous extract of Z. armatum DC. seeds on adult H. contortus worms. PMID- 27413334 TI - Outbreak of immature paramphistomosis in Nellore Jodipi sheep. AB - An outbreak of immature paramphistomosis in Nellore Jodipi sheep was recorded in Nellore district of Andhra Pradesh in 158 sheep during the months of April-June 2012. The condition is diagnosed as immature paramphistomosis on the basis of symptoms, dung sample examination and necropsy findings. The infected sheep exhibited symptoms like persistent foetid, blackish diarrhoea, sub maxillary edema, dehydration and death. Necropsy findings include hemorrhagic thickening and necrosis of proximal duodenal mucosa, ascites, gelatinization of subcutaneous and renal fat. Duodenal scrapings revealed large number of immature paramphistomes under low power microscopy. Recovery of ailing sheep was observed after oral treatment of niclosamide @ of 100 mg/kg bwt along with supportive therapy. PMID- 27413335 TI - Adult filarial worm from the breast aspirate of a young man. AB - Microfilariae and adult filarial worm have been incidentally detected in fine needle aspirates of various lesions in clinically unsuspected cases. Here we report a male patient who presented with a tender breast nodule and single enlarged lymph node. Fine Needle Aspiration (FNA) yielded 1 ml of yellow coloured fluid and single thread like worm measuring 6 * 0.2 cm. A diagnosis of breast abscess with a worm morphologically consistent with filariasis was offered. A follow up visit after 2 months showed regression of the breast lesion and the lymph node. Filariasis of the breast is an uncommon condition and can cause a diagnostic dilemma at times. FNA cytology appears to be a more convenient and effective diagnostic tool in patients with mass lesions. Demonstration and identification of the parasite in smears helps in avoiding surgical excision and early institution of prompt therapy especially in young patients. PMID- 27413336 TI - Evaluation of Kumaon hill goats for resistance to natural infection with gastrointestinal nematodes. AB - The present study deals with the investigation of different degrees of genetic resistance/resilience of Uttarakhand hill goats to natural infection with gastrointestinal nematodes in order to introduce into breeding schemes. Animals were naturally infected with Haemonchus contortus, Teladorsagia circumcincta, Oesophagostomum spp. and Trichostrongylus spp. Faecal egg counts (FEC) were carried out every month for a period of 1 year and blood samples were collected every third month for the determination of indicator traits such as FEC, packed cell volume (PCV) and haemoglobin (Hb). The mean egg per gram (EPG), PCV and Hb were 1,579.6 +/- 346, 35.12 +/- 1.1 and 8.7 +/- 0.2, respectively. The goats were divided into three groups (<800, 801-2,000 and >2,000) based on EPG. The EPG showed a negative correlation with both Hb and PCV (P < 0.01). Therefore, it was concluded that the Hb and PCV value would decrease, if EPG increases. PMID- 27413337 TI - Occurrence of Hyalomma, (Acari: Ixodidae) Koch, 1844 on domestic animal in the Union Territory of Dadra & Nagar Haveli, Indian. AB - In response to recent outbreak of Crimean-Congo hemorrhagic fever (CCHF) in Gujarat (India). This investigation was carried out in order to determine the risk of CCHF. The prevalence and abundance of Hyalomma (Acari: Ixodidae) were recorded on the domestic animals in the Union territory of Dadra & Nagar Haveli during the period of January to December 2012. Overall, 71 larva and 148 adults belonging to three species of Hyalomma viz., Hyal. anatolicum anatolicum, Hyal. detritum, and Hyal. marginatum isaaci were collected from 33 infested domestic mammals (Goats, Cows, Buffalos, Dogs and Cats). The infestation of Hyal. a. anatolicum and Hyal. m. isaaci (incriminated as the vector of CCHF virus) on cattles in these area may serious implication for human health, considering the fact that these ticks serve as vectors of CCHF. To minimize these dangers, strategic surveillance and control methods could be useful in the control of ticks recorded during the survey. PMID- 27413338 TI - Racemose variant of neurocysticercosis: a case report. AB - Neurocysticercosis is an important parasitic disease of the central nervous system and constitutes a public health challenge for most of the developing world. Radiological findings may be quite variable. A 50 year old man presented with recent onset generalized tonic-clonic seizures. CT scan revealed a lobulated cystic lesion in the right fronto-temporal lobe compressing the lateral and third ventricle and upper brainstem. Clinico-radiological diagnosis of right fronto temporal space occupying lesion with possibility of cystic glioma was made. He underwent craniotomy with cyst decompression and excision of cyst wall. Histopathology showed features of Racemose variant of Neurocysticercosis. This is an uncommon variant of neurocysticercosis characterized by extraparenchymal involvement, an aggressive clinical course and requiring surgical management. This case is being presented because of its rare occurrence and potential diagnostic difficulties on clinico-radiological grounds. PMID- 27413339 TI - Circulation of Tc Ia discrete type unit Trypanosoma cruzi in Yucatan Mexico. AB - The etiologic agent Trypanosoma cruzi (Tc) has been grouped into six discrete type units (DTU I-VI); within DTU-I exists four subgroups defined Ia-Id. In Colombia, the genotype Ia is associated with human infection and domiciliated Rhodnius vector. In the Yucatan Peninsula of Mexico, the main vector involved in T. cruzi transmission is Triatoma dimidiata predominantly via sylvatic and peridomiciliated cycles. In this study, multiple sequence analysis of mini-exon intergenic regions of T. cruzi isolates obtained from T. dimidiata in the Yucatan Peninsula of Mexico revealed they belonged to Tc Ia DTU along with two additional Mexican strains located 1,570 km away from Yucatan. In conclusion Tc Ia circulates in the Yucatan peninsula in T. dimidiata vector and likewise in the northwest region of Mexico. PMID- 27413340 TI - Occurrence of Gnathostoma spinigerum in a leopard cat from Wayanad Wildlife Sanctuary, Kerala. AB - The post-mortem examination of a leopard cat from Wayanad Wildlife Sanctuary, Kerala, died in a road accident, revealed presence of gastric tumours containing worms which were identified as Gnathostoma spinigerum based on morphological characteristics. PMID- 27413341 TI - Subcutaneous Dirofilaria repens infestation in non-descript canines. AB - Dirofilaria repens is a filarial nematode which cause subcutaneous dirofilariosis. Dogs, foxes and cats are the definitive hosts and principal reservoirs of the parasite. We report cases of D. repens infestation in non descript canines from Goa, India. The nematodes were enclosed within fibrous capsule or freely present in the tunica vaginalis of the testes, in sub-cutaneous tissue of foreleg and body cavity. The parasite showed well-developed thick multilayered cuticular ridges in the outermost layer, followed by transverse smooth muscles striations. PMID- 27413342 TI - Ascaridia galli induced ulcerative proventriculitis in a poultry bird. AB - Various possible causes of proventriculitis include virus, bacteria, fungus, protozoans, nematodes, biogenic amines and excessive copper sulphate. In the present case, parasites were found in the lumen of the proventriculus, gizzard and duodenum of a poultry bird. Characteristic features of the parasite were studied and confirmed as Ascaridia galli. An ulcerative proventriculitis evident as denuded superficial epithelium, sub-epithelial hemorrhages, infiltration of the inflammatory cells and fibrosis were seen at histopathology. Proventriculitis caused by A. galli has not been reported till date. Here, we report a case of ulcerative proventriculitis in a poultry bird caused by nematode, A. galli. PMID- 27413343 TI - Sea lice, Caligus rotundigenitalis infestations and its management in pond cultured pearlspot, Etroplus suratensis in Gujarat: a case study. AB - Highly popular and delicious fish of Kerala (India), pearlspot, Etroplus suratensis is known for its ability to tolerate wide range of salinity, omnivorous feeding behavior. Present report documents the occurrence and management of Caligus rotundigenitalis in brackishwater pond meant for culture demonstration of pearlspot in Gujarat, (India). A brackishwater aquaculture pond (1,500 sq m) was stocked with pearlspot fry (2.60 +/- 0.83 g; 4.31 +/- 0.82 cm) @ 25,000 ha(-1). On the 46th day of culture couple of dead fish were observed which gradually increased to 120 per day by 52nd day. Following the close observation parasitic infestation was noticed on gills cavities ranging from 15 to 20 numbers per fish. These characteristic features confirmed the parasite as C. rotundigenitalis. As a therapeutic measure the infested pond was successfully treated with Butox((r)) @ 300 ml/ha (Deltamethrin 12.5 mg) and repeat dose was administered 2 weeks later. The results of the study suggest the possible therapeutic value of Deltamethrin in treatment of caligid infestation in pond cultured pearlspot. PMID- 27413344 TI - A feasibility study: Use of actigraph to monitor and follow-up sleep/wake patterns in individuals attending community pharmacy with sleeping disorders. AB - INTRODUCTION: Community pharmacists are in a suitable position to give advice and provide appropriate services related to sleep disorders to individuals who are unable to easily access sleep clinics. An intervention with proper objective measure can be used by the pharmacist to assist in consultation. OBJECTIVES: The study objectives are to evaluate: (1) The effectiveness of a community pharmacy based intervention in managing sleep disorders and (2) the role of actigraph as an objective measure to monitor and follow-up individuals with sleeping disorders. METHODS AND INSTRUMENTS: The intervention care group (ICG) completed questionnaires to assess sleep scale scores (Epworth Sleepiness Scale [ESS] and Insomnia Severity Index [ISI]), wore a wrist actigraph, and completed a sleep diary. Sleep parameters (sleep efficiency in percentage [SE%], total sleep time, sleep onset latency, and number of nocturnal awakenings) from actigraphy sleep report were used for consultation and to validate sleep diary. The usual care group (UCG) completed similar questionnaires but received standard care. RESULTS: Pre- and post-mean scores for sleep scales and sleep parameters were compared between and within groups. A significant difference was observed when comparing pre- and post-mean scores for ISI in the ICG, but not for ESS. For SE%, an increase was found in the number of subjects rated as "good sleepers" at post assessment in the ICG. CONCLUSIONS: ISI scores offer insights into the development of a community pharmacy-based intervention for sleeping disorders, particularly in those with symptoms of insomnia. It also demonstrates that actigraph could provide objective sleep/wake data to assist community pharmacists during the consultation. PMID- 27413345 TI - Synthesis, characterization and in silico biological activity of some 2-(N,N dimethyl guanidinyl)-4,6-diaryl pyrimidines. AB - INTRODUCTION: As pyrimidine is a basic nucleus in DNA and RNA, it has been found to be associated with diverse biological activities. Pyrimidine derivatives were reported to possess anticonvulsant, antimicrobial, anti-inflammatory, antitumor, and antihistaminic. Recently, our team reported the anti-inflammatory and antimicrobial evaluation of some pyrimidines. OBJECTIVE: To synthesize, predict and evaluate biological activity of some 2-(N,N-dimethyl guanidinyl)-4,6-diaryl pyrimidines. EXPERIMENTAL: seven new pyrimidines were synthesized by following the standard procedures using substituted aromatic aldehydes, methyl ketones and metformin. After the biological activity was predicted using PASS, Molinspiration and Osiris property explorer, their anthelmintic activity was evaluated using Pheretima posthuma. The structural assignment of the title compounds (P1-7) has been made on the basis of elemental analysis, infrared, 1H-nuclear magnetic resonance and Mass spectral studies. RESULTS: All the synthesized compounds were found to obey Lipinski's rule. All the synthesized compounds scored good bioactivity values as GPCR ligands and kinase inhibitors. Among the test compounds, P5 was found to be more potent anthelmintic inducing paralysis in 36 48 minutes and death in 40-51 minutes. CONCLUSION AND RECOMMENDATION: The synthesized compound (P5) possessing methoxy group at position-4 of the benzene ring located at position-4 of pyrimidine exhibited good anthelmintic activity. The study revealed the necessity of synthesizing many more compounds with other substituents at position-4 of the benzene ring located at position-4 of pyrimidine. PMID- 27413346 TI - Inhibitor designing, virtual screening, and docking studies for methyltransferase: A potential target against dengue virus. AB - AIM: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. INTRODUCTION: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus. This creates an urge for new drug target identification and designing. MTase has been reported as an effective target against dengue virus as it catalyzes an essential step in methylation and capping of viral RNA for viral replication. MATERIALS AND METHODS: The crystal structure of MTase in complex with SAH was used for designing new analogs of SAH. SAH analogs designed were analyzed on the basis of docking, ADMET, and toxicity analysis done using Discovery Studio 3.5. RESULTS: Seventeen analogs found noncarcinogenic, nonmutagenic, as well as good ADMET properties and good drug-like profile. CONCLUSION: These SAH analogs, inhibitors of MTase may act as drugs against dengue virus. Further synthesis and biological testing against dengue virus is under observation. PMID- 27413347 TI - Knowledge, attitudes, and quality of life of type 2 diabetes patients in Riyadh, Saudi Arabia. AB - OBJECTIVE: The purpose of this study was to investigate the association between knowledge and attitude with health-related quality of life (HRQoL) among patients with type 2 diabetes mellitus in Riyadh, Saudi Arabia. MATERIALS AND METHODS: A cross-sectional descriptive study was undertaken with a cohort of 75 patients attending the University Diabetic Center at King Abdulaziz University Hospital, Riyadh, Saudi Arabia. The EuroQoL-five-dimensional (EQ-5D) scale was used to assess HRQoL. EQ-5D was scored using values derived from the UK general population survey. The brief diabetic knowledge test in questionnaire format developed by the University of Michigan Diabetes Research and Training Center and the attitude toward self-care questionnaire based on the diabetic care profile were used. RESULTS: Fifty-eight (77.35%) respondents were male with a mean 12.6 +/- 8.4 years of a history of diabetes. Thirty-four (45.3%) were in the age group of 45-55 years with a mean age of 54 +/- 9.2 years. A moderate level of HRQoL (0.71 +/- 0.22) was recorded in the study cohort. The mean EQ-5D score was lower in females compared to male patients (0.58 +/- 0.23 vs. 0.74 +/- 0.20). The mean score of Michigan Diabetic Knowledge Test was 8.96 +/- 2.1 and the median score was 9.00. Of 75 diabetic patients, 14.7% had poor knowledge; 72% had moderate knowledge, and only 13.3% had good knowledge. The average attitude score of all respondents was 6.38 +/- 2.11. There was a significant positive association between attitude and EQ-5D score. CONCLUSION: HRQoL and knowledge scores were moderate in type 2 diabetic patients in Riyadh, Saudi Arabia. Patient attitude toward the disease was positive, and this was positively associated with HRQoL; most respondents believed they are responsible for their care. It is likely that a high quality of diabetes self-management education program will provide benefits and affect significantly on type 2 diabetes patients in Saudi Arabia. PMID- 27413348 TI - Malaysian consumers' awareness, perception, and attitude toward cosmetic products: Questionnaire development and pilot testing. AB - BACKGROUND: Increased usage of cosmetic products has caused a growing concern about the safety of these products, and yet little is known about cosmetics from the consumers' perspective. Hence, this study's aim is to develop a valid and reliable tool for assessing consumers' awareness, perceptions, and attitudes toward cosmetic products. MATERIALS AND METHODS: A questionnaire was developed in the English language based on information collected from a literature search, in depth interviews conducted with consumers prior to this study and consultations with experts. Subsequently, the questionnaire was subjected to translation, validation, and test-retest reliability. A final version of the questionnaire was piloted among 66 consumers via convenient sampling. A descriptive analysis was performed, and the internal consistency and the differences between variables in the questionnaire were analyzed. RESULTS: The developed and translated questionnaire produced repeatable data for each of the domains (Spearman's correlation >= 0.7, P < 0.001). The internal consistency for awareness, perceptions and attitudes indicates good internal consistency (Cronbach's alpha value of more than 0.7 for each domain). Significant differences were found between the perception scores for the race, religion, and monthly expenses for cosmetic products, respectively, and the same pattern was found for the attitude scores, but monthly expenses for cosmetic products was replaced by monthly income. CONCLUSION: The results achieved via the Bahasa Malaysia questionnaire indicated that the developed and translated questionnaire can be used as a valid and reliable tool for assessing consumers' awareness, perceptions, and attitudes toward cosmetic products in Malaysia in future studies. PMID- 27413350 TI - Self-medication practices among female students of higher educational institutions in Selangor, Malaysia: A quantitative insight. AB - BACKGROUND: World Health Organization has defined self-medication as the selection and use of medications (including herbal and traditional product) by individuals to treat self-recognized illnesses or symptoms. The prevalence of self-medication is reported to be higher among female students. OBJECTIVE: To investigate the awareness and self-medication practices among female students of higher education institutions in Malaysia. METHOD: A descriptive, cross-sectional study was conducted in four higher education institutes of Selangor, Malaysia. Convenience sampling approach was used to collect data from a sample 475 students. A "pretested" questionnaire was used as a study instrument. RESULTS: A total of 461 questionnaires were returned (response rate 97.05%). The prevalence of self-medication among female students in higher educational institutions was 57.2% (n = 262). The most common source of self-prescribed medicine was a pharmacy or clinics (n = 206; 45%). It was found that antipyretics were the most common medications used without doctor's consultation (n = 212; 89.1%). Analgesics and antipyretics (n = 79; 62.7%) were highly recommended by students to their family and friends. The common reason for self-medication was prior successful experience (n = 102, 81.0%). The majority of respondents (n = 280; 61.1%) reported that they believed over-the-counter medications were as effective as medications prescribed by a doctor. CONCLUSION: The prevalence of self medication practice among female students in the sample of the four higher education institutions was moderate. More studies are required to generalize these findings across Malaysia. PMID- 27413349 TI - Amelioration of oxidative DNA damage in mouse peritoneal macrophages by Hippophae salicifolia due to its proton (H(+)) donation capability: Ex vivo and in vivo studies. AB - INTRODUCTION: The present study evaluates the antioxidant effect of methanol extract of Hippophae salicifolia (MEHS) bark with special emphasis on its role on oxidative DNA damage in mouse peritoneal macrophages. MATERIAL AND METHODS: In vitro antioxidant activity was estimated by standard antioxidant assays whereas the antioxidant activity concluded the H(+) donating capacity. Mouse erythrocytes' hemolysis and peritoneal macrophages' DNA damage were determined spectrophotometrically. In vivo antioxidant activity of MEHS was determined in carbon tetrachloride-induced mice by studying its effect on superoxide anion production in macrophages cells, superoxide dismutase in the cell lysate, DNA damage, lipid peroxidation, and reduces glutathione. RESULTS: The extract showed good in vitro antioxidant activities whereas the inhibitory concentrations values ranged from 5.80 to 106.5 MUg/ml. MEHS significantly (P < 0.05) attenuated the oxidative DNA damage. It also attenuated the oxidative conversion of hemoglobin to methemoglobin and elevation of enzymatic and nonenzymatic antioxidant in cells. CONCLUSION: The result indicates MEHS has good in vitro-in vivo antioxidant property as well as the protective effect on DNA and red blood cell may be due to its H(+) donating property. PMID- 27413351 TI - Utilization study of antidiabetic agents in a teaching hospital of Sikkim and adherence to current standard treatment guidelines. AB - OBJECTIVE: Diabetes has gradually emerged as one of the most serious public health problems in our country. This underlines the need for timely disease detection and decisive therapeutic intervention. This prospective cross-sectional observational study aims at analyzing the utilization pattern of antidiabetic agents in a remote North-East Indian tertiary care teaching hospital in the perspective of current standard treatment guidelines. MATERIALS AND METHODS: Diabetic patients receiving antidiabetic medication, both as outpatients and inpatients in our hospital over a period of 12 months (May 2013-May 2014), were included in this study. The data obtained were sorted and analyzed on the basis of gender, type of therapy, and hospital setting. RESULTS: A total of 310 patients were included in the study. Metformin was the single most frequently prescribed antidiabetic agent (66.8%) followed by the sulfonylureas group (37.4%). Insulin was prescribed in 23.2% of the patients. Combination antidiabetic drug therapy (65.1%) was used more frequently than monotherapy (34.8%). The use of biguanides (P < 0.0001) and sulfonylureas (P = 0.02) in combination was significant as compared to their use as monotherapy. A total of 48% of all antidiabetic combinations used, comprised metformin and sulfonylureas (n = 96). Insulin use was significantly higher as monotherapy and in inpatients (P < 0.0001). The utilization of drugs from the National List of Essential Medicines was 51.2%, while 11% of antidiabetics were prescribed by generic name. CONCLUSION: The pattern of utilization largely conforms to the current standard treatment guidelines. Increased use of generic drugs is an area with scope for improvement. PMID- 27413352 TI - The enlightenment from Malaysian consumers' perspective toward cosmetic products. AB - BACKGROUNDS: Variety of cosmetic products was used in our daily life, yet the amount and types of the cosmetic products used by the consumers were varied, which may be due to the different perspectives held by each of the consumers. OBJECTIVES: To explore consumers' perspectives toward cosmetic products. METHODS: An interview guide was developed with a set of 12 semistructured questions. Participants in Kuantan, Pahang were recruited via the purposive sampling, and they undergo in-depth face-to-face interviews. All of the interviews were audio recorded, transcribed verbatim, and were analyzed via thematic content analysis. RESULTS: For the awareness of cosmetic products, less aware about the cosmetic products in Malaysia were noted among the participants. In terms of perceptions about the cosmetic products, participants expressed positive perceptions toward natural cosmetic products, quality were seen as synonymous with branded products and halal certification. Next, for the attitude toward the use of cosmetic products, participants were influenced by ingredients, product brand, and halal certification. Based on personal experiences, they provide complaints and suggestions for the enhancement of cosmetic products' quality. CONCLUSIONS: Participants were found to have less awareness about the cosmetic products in Malaysia. Besides, they realized about the chemical ingredients and halal certification for the cosmetic products. Therefore, they held positive perceptions and practiced positive attitudes toward natural and halal cosmetic products. Finally, adverse reactions from the use of cosmetic products were commonly experienced by the participants, which contributed mainly by the ingredients. Thus, they hoped for serious approached to be enacted to solve this problem. PMID- 27413353 TI - Emergency contraception: Knowledge and attitude toward its use among medical students of a medical college in North-West India. AB - CONTEXT: Emergency contraception (EC) is use of drug or device to prevent pregnancy after unprotected sexual intercourse. Unlike other regular methods of contraception which are taken prior to the sexual act, EC is used after the unprotected sex. AIM: To assess the knowledge and attitude toward use of emergency contraceptives among medical students. SETTING AND DESIGN: A cross sectional questionnaire based study was conducted among all the medical students in the Government Medical College in North-West India. SUBJECTS AND METHODS: A questionnaire seeking information on knowledge and attitude of undergraduate medical students was administered over a period of 4 weeks in the month of February and March 2014. STATISTICAL ANALYSIS: The data were entered in MS excel and expressed using percentages. Chi-square test was used as a test of statistical significance. RESULTS: About 61.6% (247/401) of the participants were aware about the timing of use of EC. Audio visual media (76.6%; 307/401) was the most common source of information for of these medical students. CONCLUSIONS: The lack of appropriate in-depth knowledge of EC among future health care professional should alarm the medical teaching system as EC is the only method that can be used to prevent pregnancy after unprotected sex or contraceptive accident. PMID- 27413354 TI - Familiarity, perception, and reasons for electronic-cigarette experimentation among the general public in Malaysia: Preliminary insight. AB - OBJECTIVES: The objectives of this study were to assess the general public views and familiarity toward electronic cigarette (e-cigarette) in Kuantan, Malaysia. METHODOLOGY: A total of 277 Kuantan people were involved in this study. The questionnaire was distributed at random in shops, businesses, and public places in Kuantan. Statistical analysis was performed using SPSS (version 17.0). RESULTS: From 400 participants, a total number of 277 (160, 57.7% men and 117, 42.4% women) respondents completed the questionnaire. The mean age was 26.89 +/- 9.8 years old. The majority of the study participants were male (57.7%), Malay (83.8%), Muslims (83.8%), singles (69%), and employed (75.8%), with about 83 (29.9%) of the respondents were smokers. The prevalence of e-cigarettes smokers was found to be only 1.4% (n = 4). About one-third of the respondents (n = 72, 26%) have tried e-cigarette before. Job status was significantly associated with smoking e-cigarette among the population (P = 0.02). Main factors for a person to start e-cigarette smoking were curiosity (37.5%) and cheaper price (40.8%). Majority of respondents agreed that e-cigarette would not affect health as normal cigarette, and that variety of flavors contribute to better enjoyment (51.6% and 66.7%, respectively). CONCLUSION: The results of the current study demonstrate that the prevalence of e-cigarettes smoking and its popularity, familiarity, and knowledge are still insufficient among Kuantan population. Further studies should be done to tackle this problem before it getting worse. PMID- 27413355 TI - An evaluation of drug promotional literatures published in scientific medical journals. AB - OBJECTIVES: Evaluation and comparison of ethical standards of published drug promotional literatures (DPLs) between different Indian and non-Indian scientific medical journals regarding compliance to the World Health Organization (WHO) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMAs) guidelines. MATERIALS AND METHODS: A cross-sectional, observational study was carried out at pharmacology department. DPLs published in Indian and non-Indian scientific medical journals available at central library of medical college during the period of 6 months were collected according to selection criteria. DPLs were evaluated and compared for compliance to ethical standards of drug promotion laid by the WHO and IFPMA. Data were analyzed using Fisher's exact test. RESULTS: Out of total 178 DPLs, 103 DPLs were from Indian journals and 75 DPLs were from non-Indian journals. When compared regarding compliance to all the 11 ethical criteria of WHO, no significant difference was found between DPLs published in Indian and non-Indian journals. However, DPLs from indian journals contained significantly less information regarding dosage regimen (P = 0.0096), adverse drug reactions (P = 0.0028), warnings (P = 0.0104) and major drug interactions (P < 0.0001) as compared to non-Indian journals. Compliance to all the five IFPMA criteria was significantly higher in DPLs of non-Indian journals (88%) than Indian journals (39%) (P < 0.0001). CONCLUSION: Noncompliance to ethical standards of WHO and IFPMA guidelines is more common in DPLs of Indian journals as compared to non-Indian journals. Thus strict implementation of regulatory measures regarding DPLs published in Indian medical journals is recommended. PMID- 27413357 TI - What is the process of obtaining informed consent in a clinical trial? Is it ever justifiable to include someone in a clinical trial without prior informed consent from the individual? PMID- 27413356 TI - Enhancement of inhibitory neurotransmission and inhibition of excitatory mechanisms underlie the anticonvulsant effects of Mallotus oppositifolius. AB - CONTEXT: Mallotus oppositifolius is a shrub that is used traditionally to treat epilepsy, but its potential has not been scientifically validated. AIMS: This study investigated the anticonvulsant properties and possible mechanism of action of the 70% v/v hydroalcoholic extract of the leaves of M. oppositifolius. MATERIALS AND METHODS: Inprinting control region (ICR) mice (25-30 g) were pretreated with the M. oppositifolius leaf extract (10-100 mg/kg) before administering the respective convulsants (pentylenetetrazole [PTZ], picrotoxin [PTX], strychnine [STR], 4-aminopyridine [4-AP], and pilocarpine). The effect of the extract in maximal electroshock seizure (MES) model was investigated also. STATISTICAL ANALYSIS: Data were presented as mean +/- standard error of the mean and were analyzed with one-way analysis of variance (ANOVA) or two-way ANOVA where appropriate with Newman-Keuls or Bonferroni post hoc test respectively. P < 0.05 was considered significant. RESULTS: In both PTX and PTZ test, extract delayed the onset of seizures and reduced the frequency and duration of seizures. In the STR-induced seizure test, the extract significantly delayed the onset of seizures and reduced the duration of seizures. The extract also delayed the onset of clonic and tonic seizures as well as increasing the survival of mice in the 4 AP-induced seizure test. It further reduced the duration of tonic limb extensions in the MES test. In the pilocarpine-induced status epilepticus, the extract significantly delayed the onset of clonic convulsions and reduced the frequency and duration of seizures. Moreover, the anticonvulsant effect of the extract was attenuated by flumazenil, a benzodiazepine/gamma-aminobutyric acid (GABA) receptor antagonist. CONCLUSION: These findings show that the extract has anticonvulsant effect possible mediated by GABAergic, glycinergic neurotransmission, and potassium channel conductions. It may also be acting by antagonizing muscarinic receptor activation and N-Methyl-D-aspartate receptor activation. PMID- 27413358 TI - Pharmaceutical care to improve medication knowledge among patient with chronic kidney disease. PMID- 27413359 TI - Antiretroviral Resistance and Pregnancy Characteristics of Women with Perinatal and Nonperinatal HIV Infection. AB - Objective. To compare HIV drug resistance in pregnant women with perinatal HIV (PHIV) and those with nonperinatal HIV (NPHIV) infection. Methods. We conducted a multisite cohort study of PHIV and NPHIV women from 2000 to 2014. Sample size was calculated to identify a fourfold increase in antiretroviral (ARV) drug resistance in PHIV women. Continuous variables were compared using Student's t test and Wilcoxon rank-sum tests. Categorical variables were compared using chi (2) and Fisher's exact tests. Univariate analysis was used to determine factors associated with antiretroviral drug resistance. Results. Forty-one PHIV and 41 NPHIV participants were included. Women with PHIV were more likely to have drug resistance than those with NPHIV ((55% versus 17%, p = 0.03), OR 6.0 (95% CI 1.0 34.8), p = 0.05), including multiclass resistance (15% versus 0, p = 0.03), and they were more likely to receive nonstandard ARVs during pregnancy (27% versus 5%, p = 0.01). PHIV and NPHIV women had similar rates of preterm birth (11% versus 28%, p = 0.08) and cesarean delivery (47% versus 46%, p = 0.9). Two infants born to a single NPHIV woman acquired HIV infection. Conclusions. PHIV women have a high frequency of HIV drug resistance mutations, leading to nonstandard ARVs use during pregnancy. Despite nonstandard ARV use during pregnancy, PHIV women did not experience increased rates of adverse pregnancy outcomes. PMID- 27413361 TI - Application of Artificial Neural Network Models in Segmentation and Classification of Nodules in Breast Ultrasound Digital Images. AB - This research presents a methodology for the automatic detection and characterization of breast sonographic findings. We performed the tests in ultrasound images obtained from breast phantoms made of tissue mimicking material. When the results were considerable, we applied the same techniques to clinical examinations. The process was started employing preprocessing (Wiener filter, equalization, and median filter) to minimize noise. Then, five segmentation techniques were investigated to determine the most concise representation of the lesion contour, enabling us to consider the neural network SOM as the most relevant. After the delimitation of the object, the most expressive features were defined to the morphological description of the finding, generating the input data to the neural Multilayer Perceptron (MLP) classifier. The accuracy achieved during training with simulated images was 94.2%, producing an AUC of 0.92. To evaluating the data generalization, the classification was performed with a group of unknown images to the system, both to simulators and to clinical trials, resulting in an accuracy of 90% and 81%, respectively. The proposed classifier proved to be an important tool for the diagnosis in breast ultrasound. PMID- 27413360 TI - Multimodality Treatment in Ewing's Sarcoma Family Tumors of the Maxilla and Maxillary Sinus: Review of the Literature. AB - The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series. We hereby present a review of the literature published on ESFTs reported in the maxilla and maxillary sinus region from 1968 to 2016. PMID- 27413362 TI - Testosterone Replacement Modulates Cardiac Metabolic Remodeling after Myocardial Infarction by Upregulating PPARalpha. AB - Despite the importance of testosterone as a metabolic hormone, its effects on myocardial metabolism in the ischemic heart remain unclear. Myocardial ischemia leads to metabolic remodeling, ultimately resulting in ATP deficiency and cardiac dysfunction. In the present study, the effects of testosterone replacement on the ischemic heart were assessed in a castrated rat myocardial infarction model established by ligating the left anterior descending coronary artery 2 weeks after castration. The results of real-time PCR and Western blot analyses showed that peroxisome proliferator-activated receptor alpha (PPARalpha) decreased in the ischemic myocardium of castrated rats, compared with the sham-castration group, and the mRNA expression of genes involved in fatty acid metabolism (the fatty acid translocase CD36, carnitine palmitoyltransferase I, and medium-chain acyl-CoA dehydrogenase) and glucose transporter-4 also decreased. A decline in ATP levels in the castrated rats was accompanied by increased cardiomyocyte apoptosis and fibrosis and impaired cardiac function, compared with the sham castration group, and these detrimental effects were reversed by testosterone replacement. Taken together, our findings suggest that testosterone can modulate myocardial metabolic remodeling by upregulating PPARalpha after myocardial infarction, exerting a protective effect on cardiac function. PMID- 27413363 TI - Optimizing NEURON Simulation Environment Using Remote Memory Access with Recursive Doubling on Distributed Memory Systems. AB - Increase in complexity of neuronal network models escalated the efforts to make NEURON simulation environment efficient. The computational neuroscientists divided the equations into subnets amongst multiple processors for achieving better hardware performance. On parallel machines for neuronal networks, interprocessor spikes exchange consumes large section of overall simulation time. In NEURON for communication between processors Message Passing Interface (MPI) is used. MPI_Allgather collective is exercised for spikes exchange after each interval across distributed memory systems. The increase in number of processors though results in achieving concurrency and better performance but it inversely affects MPI_Allgather which increases communication time between processors. This necessitates improving communication methodology to decrease the spikes exchange time over distributed memory systems. This work has improved MPI_Allgather method using Remote Memory Access (RMA) by moving two-sided communication to one-sided communication, and use of recursive doubling mechanism facilitates achieving efficient communication between the processors in precise steps. This approach enhanced communication concurrency and has improved overall runtime making NEURON more efficient for simulation of large neuronal network models. PMID- 27413364 TI - A Fast Framework for Abrupt Change Detection Based on Binary Search Trees and Kolmogorov Statistic. AB - Change-Point (CP) detection has attracted considerable attention in the fields of data mining and statistics; it is very meaningful to discuss how to quickly and efficiently detect abrupt change from large-scale bioelectric signals. Currently, most of the existing methods, like Kolmogorov-Smirnov (KS) statistic and so forth, are time-consuming, especially for large-scale datasets. In this paper, we propose a fast framework for abrupt change detection based on binary search trees (BSTs) and a modified KS statistic, named BSTKS (binary search trees and Kolmogorov statistic). In this method, first, two binary search trees, termed as BSTcA and BSTcD, are constructed by multilevel Haar Wavelet Transform (HWT); second, three search criteria are introduced in terms of the statistic and variance fluctuations in the diagnosed time series; last, an optimal search path is detected from the root to leaf nodes of two BSTs. The studies on both the synthetic time series samples and the real electroencephalograph (EEG) recordings indicate that the proposed BSTKS can detect abrupt change more quickly and efficiently than KS, t-statistic (t), and Singular-Spectrum Analyses (SSA) methods, with the shortest computation time, the highest hit rate, the smallest error, and the highest accuracy out of four methods. This study suggests that the proposed BSTKS is very helpful for useful information inspection on all kinds of bioelectric time series signals. PMID- 27413365 TI - High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea. AB - Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4-6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6 90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance. PMID- 27413367 TI - Tacrolimus for Remission Induction and Maintenance Therapy in Patients with Ulcerative Colitis: A Retrospective Evaluation Study. AB - Background. In this retrospective study, we compared the efficacy of tacrolimus (TAC) or prednisolone (PSL) for maintenance therapy in patients with ulcerative colitis (UC) at remission. Methods. The study patients were followed up for at least one year after induction of remission with either PSL (n = 55, between April 2004 and March 2014) or TAC (n = 40, between April 2009 and March 2014). The clinical features and relapse rates were compared in the two groups. Maintenance therapy in the TAC group included TAC alone, AZA alone, and TAC plus AZA. Results. The recurrence rates at 1500 days after remission were 61% and 46% for the PSL and TAC groups, respectively (P < 0.05). The recurrence rates at 600 days for TAC, AZA, and TAC + AZA maintenance groups were 24%, 49%, and 55%, respectively. Nephrotoxicity developed in 16 patients on TAC maintenance therapy. Conclusions. TAC monotherapy is a potential alternative especially for PSL nonresponders or those intolerant to AZA. However, patients on TAC therapy should be regularly monitored for adverse effects including nephrotoxicity. PMID- 27413366 TI - Risk and Surveillance of Cancers in Primary Biliary Tract Disease. AB - Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases. PMID- 27413368 TI - Severity of Lower Urinary Tract Symptoms among Middle Aged and Elderly Nigerian Men: Impact on Quality of Life. AB - Objectives. To compare the severity of LUTS among middle aged and elderly Nigerian men and determine the influence of LUTS severity on QoL. Methods. This cross-sectional study was conducted among new patients presenting with LUTS attending Urology clinic between 2011 and 2015. Assessment of symptoms was based on IPSS and bother score completed by the eligible subjects on the same day of their clinic visits. Results. Four hundred patients were studied comprising 229 middle aged and 171 elderly men. Interquartile range (IQR) of IPSS scores for men <65 years and those >=65 years was 14.0 (16.0) and 19 (15.0), respectively (p < 0.001). Mild LUTS was significantly associated with best, good, and poor quality of life while moderate LUTS was associated with poor QoL. Severe LUTS was significantly associated with all the categories of QoL (Best-Worst). Among the cohort of subjects with poor QoL, elderly patients had a significantly higher median IPSS score (p < 0.05). Conclusions. There is no level of severity of LUTS in which patients' QoL is not impaired although mild symptomatology may be associated with better QoL and severe symptomatology with poor QoL. Careful attention to QoL may help identify patients who require early and prompt treatment irrespective of the IPSS. PMID- 27413369 TI - Multiphase Simulated Annealing Based on Boltzmann and Bose-Einstein Distribution Applied to Protein Folding Problem. AB - A new hybrid Multiphase Simulated Annealing Algorithm using Boltzmann and Bose Einstein distributions (MPSABBE) is proposed. MPSABBE was designed for solving the Protein Folding Problem (PFP) instances. This new approach has four phases: (i) Multiquenching Phase (MQP), (ii) Boltzmann Annealing Phase (BAP), (iii) Bose Einstein Annealing Phase (BEAP), and (iv) Dynamical Equilibrium Phase (DEP). BAP and BEAP are simulated annealing searching procedures based on Boltzmann and Bose Einstein distributions, respectively. DEP is also a simulated annealing search procedure, which is applied at the final temperature of the fourth phase, which can be seen as a second Bose-Einstein phase. MQP is a search process that ranges from extremely high to high temperatures, applying a very fast cooling process, and is not very restrictive to accept new solutions. However, BAP and BEAP range from high to low and from low to very low temperatures, respectively. They are more restrictive for accepting new solutions. DEP uses a particular heuristic to detect the stochastic equilibrium by applying a least squares method during its execution. MPSABBE parameters are tuned with an analytical method, which considers the maximal and minimal deterioration of problem instances. MPSABBE was tested with several instances of PFP, showing that the use of both distributions is better than using only the Boltzmann distribution on the classical SA. PMID- 27413370 TI - Vitamin D Status Is Negatively Correlated with Insulin Resistance in Chinese Type 2 Diabetes. AB - Objectives. Vitamin D deficiency plays a role in insulin resistance and the pathogenesis of type 2 diabetes mellitus. Little information is available about the association between vitamin D status and insulin resistance in the Chinese population. Currently, vitamin D status is evaluated by the concentrations of serum 25-hydroxyvitamin D [25(OH)D]. This study explores the relationship between insulin resistance and serum 25-hydroxyvitamin D concentrations in Chinese patients with type 2 diabetes mellitus. Subjects and Methods. This study included 117 patients with type 2 diabetes. The following variables were measured: 25 hydroxyvitamin D [25(OH)D], glycosylated hemoglobin A1c (HbA1c), fasting blood glucose (FBS), fasting blood insulin (FINS), fasting blood C-peptide, serum creatinine (SCr), glomerular filtration rate (eGFR), body mass index (BMI), and homeostatic model estimates of insulin resistance (HOMA-IR). Results. The cases were divided into three groups: Group 1 (G1) with 25(OH)D <= 20 ng/mL [<=50 nmol/L], Group 2 (G2) with 25(OH)D values from 20 ng/mL [50 nmol/L] to 30 ng/mL [75 nmol/L], and Group 3 (G3) with 25(OH)D >= 30 ng/mL [>=75 nmol/L], with 52.6%, 26.3%, and 21.1% of subjects in Groups 1-3, respectively. There was a negative correlation between 25(OH)D and HOMA-IR (beta = -0.314, p = 0.001) adjusted by age, BMI, and eGFR. Conclusion. Better vitamin D status may be protective of glucose homeostasis since 25(OH)D was negatively associated with insulin resistance in Chinese patients with type 2 diabetes. PMID- 27413371 TI - Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome. AB - Objective. Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: 13.7 +/- 3.8 years) KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT). Results. KS children and adolescents showed significantly reduced AD SoS (p < 0.005) and BTT (p < 0.0005) z-scores compared to the controls. However, KS patients presented significantly higher PTH (p < 0.0001) and significantly lower 25(OH)D (p < 0.0001), osteocalcin (p < 0.05), and bone alkaline phosphatase levels (p < 0.005). Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages. PMID- 27413372 TI - Total Endoscopic Thyroidectomy with Intraoperative Laryngeal Nerve Monitoring. AB - Objective. To evaluate the clinical efficacy of laryngeal nerve (LN) monitoring (LNM) during total endoscopic thyroidectomy via breast approach, with emphasis on the identification rates for RLN and EBSLN and the incidence of RLN paralysis. Materials and Methods. This retrospective study included 280 patients who underwent endoscopic thyroidectomy with or without LNM. RLN and EBSLN were identified using endoscopic magnification in the control group, while they were localized additionally by LNM in the LNM group. Demographic parameters and surgical outcomes were analyzed by statistical methods. Patients in the control group were also stratified by the side of thyroidectomy to determine difference in left and right RLN injury rates. Results. All procedures were successfully conducted without permanent LN damage. The identification rates for RLN and EBSLN were high in the LNM group compared to those of the control group, and the risk difference (RD) of temporary RLN injury between two groups was 6.3%. The risk of damage was slightly higher for the left RLN than for the right RLN in the control group, which was performed by a right-hand surgeon. Conclusion. The joint application of LNM and endoscopic magnified view endows total endoscopic thyroidectomy with ease, safety, and efficiency. PMID- 27413373 TI - Predictive Factors of Development of Graves' Ophthalmopathy for Patients with Juvenile Graves' Disease. AB - Background. Due to low incidence of Graves' ophthalmopathy (GO) among children, the manifestation is poorly analyzed, posing a risk to late identification of insidious disease. Purposes. To identify predictive factors that may influence the development of GO in pediatric and young patients with Graves' disease (GD). Methods. A cross-sectional study of patients newly diagnosed with pediatric or juvenile GD during 2002-2012 was conducted at the Hospital of Lithuanian University of Health Sciences. Ocular evaluation was based on European Group on Graves' Orbitopathy survey. The ocular manifestations were analyzed in relation to demographic, environmental, and clinical factors. Results. In total, 130 patients with juvenile GD were included; 29.2% had GO. Median age at GD onset was 17 yrs (IQR 4-29). Main symptoms of GO were eyelids retraction (73.7%), proptosis (65.8%), injection of conjunctiva (42.1%), and eyeball motility disturbance (21.1%). Major significant and independent risk factors for GO development were high initial concentration of FT4 (OR = 5.963), TTHAb (OR = 6.358), stress (OR = 6.030), and smoking (OR = 7.098). Conclusion. The major factors that could influence GO development were smoking, stress, and increased levels of initial TRAb, FT4. Slight proptosis, retraction of eyelids, and conjunctive injection were found as predominant ophthalmological symptoms in juvenile GO. PMID- 27413374 TI - Molecular and Phylogenetic Analysis of Bovine Papillomavirus Type 1: First Report in Iraqi Cattle. AB - This study aimed to provide the first molecular characterization of bovine papillomavirus type 1 (BPV-1) in Iraq. BPV is a widely spread oncogenic virus in Iraqi cattle and is associated with the formation of both benign and malignant lesions, resulting in notable economic losses in dairy and beef cattle. In the current study, 140 cutaneous papilloma specimens were collected from cattle in central Iraq. These samples were submitted to histopathological examination, PCR, and sequencing analysis. The histopathology revealed that the main lesion type among the specimens was fibropapilloma. BPV-1 DNA was detected in 121 of the samples (86.42%) in Iraqi cattle as the main causative agent for the disease. A partial sequence for the E2, L2 genes, and complete sequence for the E5 gene were deposited in GenBank. Phylogenetic analysis confirmed the presence of BPV-1 and showed that the origin of infection may be imported European cattle. Obtaining a complete E5 gene sequence enabled us to perform structural predictions. This study presents the first report of BPV-1 infection in the Iraqi cattle and contributes to extending the knowledge of the origin of the spread of this disease. The results of this study will aid in the development of appropriate control measures and therapeutic strategies. PMID- 27413375 TI - Recent Advances in the Synthesis and Stabilization of Nickel and Nickel Oxide Nanoparticles: A Green Adeptness. AB - Green protocols for the synthesis of nanoparticles have been attracting a lot of attention because they are eco-friendly, rapid, and cost-effective. Nickel and nickel oxide nanoparticles have been synthesized by green routes and characterized for impact of green chemistry on the properties and biological effects of nanoparticles in the last five years. Green synthesis, properties, and applications of nickel and nickel oxide nanoparticles have been reported in the literature. This review summarizes the synthesis of nickel and nickel oxide nanoparticles using different biological systems. This review also provides comparative overview of influence of chemical synthesis and green synthesis on structural properties of nickel and nickel oxide nanoparticles and their biological behavior. It concludes that green methods for synthesis of nickel and nickel oxide nanoparticles are better than chemical synthetic methods. PMID- 27413376 TI - Erratum to "The Characteristics and Significance of Locally Infiltrating B Cells in Lupus Nephritis and Their Association with Local BAFF Expression". AB - [This corrects the article DOI: 10.1155/2013/954292.]. PMID- 27413377 TI - Client Satisfaction with Delivery Care Service and Associated Factors in the Public Health Facilities of Gamo Gofa Zone, Southwest Ethiopia: In a Resource Limited Setting. AB - Background. Ensuring patient satisfaction is an important means of secondary prevention of maternal mortality. This study presents findings from a multidimensional study of client satisfaction from the Gamo Gofa Zone in Southwest Ethiopia. Methods. A facility based cross-sectional study using exit interviews was conducted from 2014. Client satisfaction was measured using a survey adopted from the Donabedian quality assessment framework. Thirteen health institutions were randomly sampled of 66 institutions in Gamo Gofa Zone. Logistic regression was used to determine predictors of client satisfaction. Results. The overall satisfaction level of the clients in this study was 79.1% with (95% CI; 75-82). Women attending health centres were more likely satisfied than women attending hospitals (chi (2) = 83.7, df = 12, P < 0.001). The proportion of women who complained about an unfriendly attitude or unresentful care from health workers was higher in the hospitals (chi (2) = 27.4, df = 1, P < 0.001). The presence of support persons during child birth improved client satisfaction (AOR = 6.23 95% CI; 2.75-14.1) and women who delivered with caesarean section are four times more likely satisfied than those who deliver vaginally (AOR 3.6 95% CI; 1.44-9.06). Client satisfaction was reduced if the women had to pay for the services (AOR = 0.27 95% CI; 0.09-81). Conclusions. The study shows that overall satisfaction level is good. More emphasis should be put on giving women friendly care, particularly at the hospitals. PMID- 27413378 TI - Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells. AB - Late outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo expansion before they could provide a practical cell therapy and it is currently unclear if they would home and engraft to an injury site. Using an in vitro flow system we studied LO-EPC under simulated injury conditions including EC activation, ischaemia, disrupted EC integrity, and exposed basement membrane. Perfused LO-EPC adhered to discontinuous EC paracellularly at junctional regions between adjacent cells under shear stress 0.7 dyn/cm(2). The interaction was not adhesion molecule dependent and not enhanced by EC activation. LO-EPC expressed high levels of the VE-Cadherin which may explain these findings. Ischaemia reperfusion injury decreased the interaction with LO-EPC due to cell retraction. LO-EPC interacted with exposed extracellular matrix (ECM) proteins, fibronectin and vitronectin. The interaction was mediated by integrins alpha5beta3, alphavbeta1, and alphavbeta3. This study has demonstrated that an injured local environment presents sufficient adhesive signals to capture flow perfused LO-EPC in vitro and that LO-EPC have properties consistent with their potential role in vascular repair. PMID- 27413379 TI - Restoration of Polyamine Metabolic Patterns in In Vivo and In Vitro Model of Ischemic Stroke following Human Mesenchymal Stem Cell Treatment. AB - We investigated changes in PA levels by the treatment of human bone-marrow derived mesenchymal stem cells (hBM-MSCs) in ischemic stroke in rat brain model and in cultured neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD). In ischemic rat model, transient middle cerebral artery occlusion (MCAo) was performed for 2 h, followed by intravenous transplantation of hBM-MSCs or phosphate-buffered saline (PBS) the day following MCAo. Metabolic profiling analysis of PAs was examined in brains from three groups: control rats, PBS treated MCAo rats (MCAo), and hBM-MSCs-treated MCAo rats (MCAo + hBM-MSCs). In ischemic cell model, SH-SY5Y cells were exposed to OGD for 24 h, treated with hBM MSCs (OGD + hBM-MSCs) prior to continued aerobic incubation, and then samples were collected after coculture for 72 h. In the in vivo MCAo ischemic model, levels of some PAs in brain samples of the MCAo and MCAo + hBM-MSCs groups were significantly different from those of the control group. In particular, putrescine, cadaverine, and spermidine in brain tissues of the MCAo + hBM-MSCs group were significantly reduced in comparison to those in the MCAo group. In the in vitro OGD system, N (1)-acetylspermidine, spermidine, N (1)-acetylspermine, and spermine in cells of the OGD + hBM-MSCs group were significantly reduced compared to those of OGD group. PMID- 27413380 TI - Bone Formation from Porcine Dental Germ Stem Cells on Surface Modified Polybutylene Succinate Scaffolds. AB - Designing and providing a scaffold are very important for the cells in tissue engineering. Polybutylene succinate (PBS) has high potential as a scaffold for bone regeneration due to its capacity in cell proliferation and differentiation. Also, stem cells from 3rd molar tooth germs were favoured in this study due to their developmentally and replicatively immature nature. In this study, porcine dental germ stem cells (pDGSCs) seeded PBS scaffolds were used to investigate the effects of surface modification with fibronectin or laminin on these scaffolds to improve cell attachment, proliferation, and osteogenic differentiation for tissue engineering applications. The osteogenic potentials of pDGSCs on these modified and unmodified foams were examined to heal bone defects and the effects of fibronectin or laminin modified PBS scaffolds on pDGSC differentiation into bone were compared for the first time. For this study, MTS assay was used to assess the cytotoxic effects of modified and unmodified surfaces. For the characterization of pDGSCs, flow cytometry analysis was carried out. Besides, alkaline phosphatase (ALP) assay, von Kossa staining, real-time PCR, CM-Dil, and immunostaining were applied to analyze osteogenic potentials of pDGSCs. The results of these studies demonstrated that pDGSCs were differentiated into osteogenic cells on fibronectin modified PBS foams better than those on unmodified and laminin modified PBS foams. PMID- 27413381 TI - Spectrum of Opportunistic Fungal Infections in HIV/AIDS Patients in Tertiary Care Hospital in India. AB - HIV related opportunistic fungal infections (OFIs) continue to cause morbidity and mortality in HIV infected patients. The objective for this prospective study is to elucidate the prevalence and spectrum of common OFIs in HIV/AIDS patients in north India. Relevant clinical samples were collected from symptomatic HIV positive patients (n = 280) of all age groups and both sexes and subjected to direct microscopy and fungal culture. Identification as well as speciation of the fungal isolates was done as per the standard recommended methods. CD4+T cell counts were determined by flow cytometry using Fluorescent Activated Cell Sorter Count system. 215 fungal isolates were isolated with the isolation rate of 41.1%. Candida species (86.5%) were the commonest followed by Aspergillus (6.5%), Cryptococcus (3.3%), Penicillium (1.9%), and Alternaria and Rhodotorula spp. (0.9% each). Among Candida species, Candida albicans (75.8%) was the most prevalent species followed by C. tropicalis (9.7%), C. krusei (6.4%), C. glabrata (4.3%), C. parapsilosis (2.7%), and C. kefyr (1.1%). Study demonstrates that the oropharyngeal candidiasis is the commonest among different OFIs and would help to increase the awareness of clinicians in diagnosis and early treatment of these infections helping in the proper management of the patients especially in resource limited countries like ours. PMID- 27413382 TI - Clinical and Laboratory Diagnosis of Buruli Ulcer Disease: A Systematic Review. AB - Background. Buruli ulcer (BU) is a necrotizing cutaneous infection caused by Mycobacterium ulcerans. Early diagnosis is crucial to prevent morbid effects and misuse of drugs. We review developments in laboratory diagnosis of BU, discuss limitations of available diagnostic methods, and give a perspective on the potential of using aptamers as point-of-care. Methods. Information for this review was searched through PubMed, web of knowledge, and identified data up to December 2015. References from relevant articles and reports from WHO Annual Meeting of the Global Buruli Ulcer initiative were also used. Finally, 59 articles were used. Results. The main laboratory methods for BU diagnosis are microscopy, culture, PCR, and histopathology. Microscopy and PCR are used routinely for diagnosis. PCR targeting IS2404 is the gold standard for laboratory confirmation. Culture remains the only method that detects viable bacilli, used for diagnosing relapse and accrued isolates for epidemiological investigation as well as monitoring drug resistance. Laboratory confirmation is done at centers distant from endemic communities reducing confirmation to a quality assurance. Conclusions. Current efforts aimed at developing point-of-care diagnostics are saddled with major drawbacks; we, however, postulate that selection of aptamers against MU target can be used as point of care. PMID- 27413383 TI - Mollicutes/HIV Coinfection and the Development of AIDS: Still Far from a Definitive Response. AB - Background. Mycoplasmas are known to cause various infections in humans, mainly in the respiratory and urogenital tracts. The different species are usually host specific and cause diseases in well-defined sites. New species have been isolated, including those from HIV-infected persons. Summary. Its in vitro properties, combined with clinical findings, have led to the hypothesis that these microorganisms may act as cofactors of HIV in AIDS development. Even today this point of view is quite polemic among infectious disease specialists and many aspects remain to be clarified, in contrast to what happens, for instance, with HIV/Mycobacterium tuberculosis coinfection. Dozens of papers have been published covering aspects of Mollicutes/HIV coinfection, but they add little to no information about the putative contribution of Mollicutes to the evolution of AIDS. Very few researchers have devoted their efforts to trying to answer this question, which remains open. In this review, we discuss the evidences that may support this statement in the light of current knowledge in the field of mycoplasmology. PMID- 27413384 TI - Synergistic Effect of Ferulic Acid and Z-Ligustilide, Major Components of A. sinensis, on Regulating Cold-Sensing Protein TRPM8 and TPRA1 In Vitro. AB - Angelica sinensis has been used to attenuate cold-induced cutaneous vasospasm syndrome, such as Raynaud's disease and frostbite, in China for many years. Ferulic acid (PubChem CID: 445858) and Z-ligustilide (PubChem CID: 529865), two major components extracted from Angelica sinensis, had been reported to inhibit vasoconstriction induced by vasoconstrictors. In this study, the pharmacological interaction in regulating cold-induced vascular smooth muscle cell contraction via cold-sensing protein TRPM8 and TRPA1 was analyzed between ferulic acid and Z ligustilide. Pharmacological interaction on inhibiting [Ca(2+)]i influx evoked by TRPM8 agonist WS-12 or TRPA1 agonist ASP 7663 as well as cold-induced upregulation of TRPM8 was determined using isobolographic analysis. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction. Combination effect of two components in inhibiting RhoA activation and phosphorylation of MLC20 induced by WS-12 or ASP 7663 was also being quantified. These findings suggest that the therapeutic effect of Angelica sinensis on cold-induced vasospasm may be partially attributed to combinational effect, via TRPM8 and TPRA1 way, between ferulic acid and Z ligustilide. PMID- 27413385 TI - Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats. AB - To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c Src, and p85alpha were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85alpha, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID- 27413386 TI - Qingchang Wenzhong Decoction Ameliorates Dextran Sulphate Sodium-Induced Ulcerative Colitis in Rats by Downregulating the IP10/CXCR3 Axis-Mediated Inflammatory Response. AB - Qingchang Wenzhong Decoction (QCWZD) is an effective traditional Chinese medicine prescription. Our previous studies have shown that QCWZD has significant efficacy in patients with mild-to-moderate ulcerative colitis (UC) and in colonic mucosa repair in UC rat models. However, the exact underlying mechanism remains unknown. Thus, this study was conducted to determine QCWZD's efficacy and mechanism in dextran sulphate sodium- (DSS-) induced UC rat models, which were established by 7-day administration of 4.5% DSS solution. QCWZD was administered daily for 7 days, after which the rats were euthanized. Disease activity index (DAI), histological score (HS), and myeloperoxidase (MPO) level were determined to evaluate UC severity. Serum interferon gamma-induced protein 10 (IP10) levels were determined using ELISA kits. Western blotting and real-time polymerase chain reaction were, respectively, used to determine colonic protein and gene expression of IP10, chemokine (cys-x-cys motif) receptor (CXCR)3, and nuclear factor- (NF-) kappaB p65. Intragastric QCWZD administration ameliorated DSS induced UC, as evidenced by decreased DAI, HS, and MPO levels. Furthermore, QCWZD decreased the protein and gene expression of IP10, CXCR3, and NF-kappaB p65. Overall, these results suggest that QCWZD ameliorates DSS-induced UC in rats by downregulating the IP10/CXCR3 axis-mediated inflammatory response and may be a novel UC therapy. PMID- 27413387 TI - A Systematic Review and Meta-Analysis Estimating the Expected Dropout Rates in Randomized Controlled Trials on Yoga Interventions. AB - A reasonable estimation of expected dropout rates is vital for adequate sample size calculations in randomized controlled trials (RCTs). Underestimating expected dropouts rates increases the risk of false negative results while overestimating rates results in overly large sample sizes, raising both ethical and economic issues. To estimate expected dropout rates in RCTs on yoga interventions, MEDLINE/PubMed, Scopus, IndMED, and the Cochrane Library were searched through February 2014; a total of 168 RCTs were meta-analyzed. Overall dropout rate was 11.42% (95% confidence interval [CI] = 10.11%, 12.73%) in the yoga groups; rates were comparable in usual care and psychological control groups and were slightly higher in exercise control groups (rate = 14.53%; 95% CI = 11.56%, 17.50%; odds ratio = 0.82; 95% CI = 0.68, 0.98; p = 0.03). For RCTs with durations above 12 weeks, dropout rates in yoga groups increased to 15.23% (95% CI = 11.79%, 18.68%). The upper border of 95% CIs for dropout rates commonly was below 20% regardless of study origin, health condition, gender, age groups, and intervention characteristics; however, it exceeded 40% for studies on HIV patients or heterogeneous age groups. In conclusion, dropout rates can be expected to be less than 15 to 20% for most RCTs on yoga interventions. Yet dropout rates beyond 40% are possible depending on the participants' sociodemographic and health condition. PMID- 27413388 TI - Herbal Medicines for Treating Metabolic Syndrome: A Systematic Review of Randomized Controlled Trials. AB - Objective. The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines in the management of metabolic syndrome. Materials and Methods. On December 9, 2015, we searched PubMed, EMBASE, Cochrane Library, SCOPUS, AMED, CNKI, KoreaMed, KMBASE, OASIS, and J-STAGE with no restriction on language or published year. We selected randomized controlled trials that involved patients with metabolic syndrome being treated with herbal medicines as intervention. The main keywords were "Chinese herbal medicines", "metabolic syndrome", and "randomized controlled trials". Herbal substances which were not based on East Asian medical theory, combination therapy with western medicines, and concurrent diseases other than metabolic syndrome were excluded. The risk of bias was assessed by Cochrane's "Risk of Bias" tool. The protocol or review was registered in PROSPERO (an international prospective register of systematic reviews) (CRD42014006842). Results. From 1,098 articles, 12 RCTs were included in this review: five trials studied herbal medicines versus a placebo or no treatment, and seven trials studied herbal medicines versus western medicines. Herbal medicines were effective on decreasing waist circumference, blood glucose, blood lipids, and blood pressure. Conclusion. This study suggests the possibility that herbal medicines can be complementary and alternative medicines for metabolic syndrome. PMID- 27413390 TI - Sedative and Anxiolytic-Like Actions of Ethanol Extract of Leaves of Glinus oppositifolius (Linn.) Aug. DC. AB - Glinus oppositifolius is a small herb, widely used in the traditional medicine of Bangladesh in treatment of a variety of diseases and disorders such as insomnia, pain, inflammation, jaundice, and fever. The present study evaluated the sedative and anxiolytic potentials of the ethanol extract of leaves of G. oppositifolius (EEGO) in different behavioral models in mice. The sedative activity of EEGO was investigated using hole cross, open field, rotarod, and thiopental sodium- (TS-) induced sleeping time determination tests, where the elevated plus maze (EPM) and light-dark box (LDB) exploration tests were employed to justify the anxiolytic potentials in mice at the doses of 50, 100, and 200 mg/kg. The results demonstrated that EEGO significantly inhibited the exploratory behavior of the animals both in hole cross and in open field tests in a dose-dependent manner. It also decreased motor coordination and modified TS-mediated hypnosis in mice. In addition, EEGO showed anxiolytic potential by increasing the number and time of entries in the open arm of EPM, which is further strengthened by increase in total time spent in the light part of LDB. Therefore, this study suggests the sedative and anxiolytic properties of the leaves of G. oppositifolius and supports the traditional use of this plant in treatment of different psychiatric disorders including insomnia. PMID- 27413389 TI - Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters. AB - The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA) and water-EtOH soluble fraction (Fraction B, FB) prepared from the Danzhi-xiaoyao-san (DZXYS) by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats. PMID- 27413391 TI - Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro. AB - Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots) extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant beta-carotene (414 +/- 12 ng/g of extract) and phytochemicals such as total polyphenols (12.0 +/- 1.1 mg gallic acid equivalent/g of extract) and flavonoids (11.0 +/- 1.4 mg catechin equivalent/g of extract). The antioxidant potential of the extract was assessed by its DPPH- (2,2-diphenyl-1-picrylhydrazyl-) free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton's reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress-induced hemolysis and damage of blood vessels and other tissues. PMID- 27413392 TI - Human Activity Recognition in AAL Environments Using Random Projections. AB - Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject's body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL), for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD) data are presented. PMID- 27413393 TI - A Multiphase Flow in the Antroduodenal Portion of the Gastrointestinal Tract: A Mathematical Model. AB - A group of authors has developed a multilevel mathematical model that focuses on functional disorders in a human body associated with various chemical, physical, social, and other factors. At this point, the researchers have come up with structure, basic definitions and concepts of a mathematical model at the "macrolevel" that allow describing processes in a human body as a whole. Currently we are working at the "mesolevel" of organs and systems. Due to complexity of the tasks, this paper deals with only one meso-fragment of a digestive system model. It describes some aspects related to modeling multiphase flow in the antroduodenal portion of the gastrointestinal tract. Biochemical reactions, dissolution of food particles, and motor, secretory, and absorbing functions of the tract are taken into consideration. The paper outlines some results concerning influence of secretory function disorders on food dissolution rate and tract contents acidity. The effect which food density has on inflow of food masses from a stomach to a bowel is analyzed. We assume that the future development of the model will include digestive enzymes and related reactions of lipolysis, proteolysis, and carbohydrates breakdown. PMID- 27413394 TI - Safety in selective surgical exploration in penetrating neck trauma. AB - BACKGROUND: Selective management of penetrating neck injuries has been considered the standard of care with minimal risks to patient safety. In a previous non randomized prospective study conducted at our center, selective management proved to be safe and reduced unnecessary exploratory cervicotomies. In the present study, the role of clinical examination and selective diagnostic tests were assessed by reviewing demographic and clinical data. A comparison of results between two groups (mandatory surgical exploration versus selective surgical exploration) was made to check the safety of selective management in terms of the rates of morbidity and mortality. METHODS: A retrospective analysis at the Emergency Department of the Hospital das Clinicas of the University of Sao Paulo was performed by a chart review of our trauma registry, identifying 161 penetrating neck trauma victims. RESULTS: Of the 161 patients, 81.6 % were stabbed and 18.4 % had gunshot injuries. Stratifying the wound entry points by neck zones, we observed that zone I was penetrated in 32.8 %, zone II in 44.1 % and zone III in 23.1 % of all the cases. Thirty one patients (19.2 %) had immediate surgical exploration, which had a mean length of stay of 6 days, a complication rate of 12.9 % and a mortality rate of 9.4 %. Of the 130 who underwent selective surgical exploration 34 (26.1 %) required operative procedures after careful physical examination and diagnostic testing based on clinical indications. The mean length of stay for the selective surgical exploration group was 2 days with a complication rate of 17.6 % with no mortality, and virtually all of them were related to associated injuries in distant body segment. No statistical significance was found comparing mortality and complication rates between the two groups. Selective approach avoided 59 % of unnecessary exploratory cervicotomies. CONCLUSION: Careful evaluation of asymptomatic and stable patients with minor signs of injury can safely avoid unnecessary neck explorations with low rates of morbidity. This should be the standard management of such patients. PMID- 27413396 TI - Erratum to: The Salmonella pathogenicity island 13 contributes to pathogenesis in streptomycin pre-treated mice but not in day-old chickens. AB - [This corrects the article DOI: 10.1186/s13099-016-0098-0.]. PMID- 27413395 TI - Absence of genomic hypomethylation or regulation of cytosine-modifying enzymes with aging in male and female mice. AB - BACKGROUND: Changes to the epigenome with aging, and DNA modifications in particular, have been proposed as a central regulator of the aging process, a predictor of mortality, and a contributor to the pathogenesis of age-related diseases. In the central nervous system, control of learning and memory, neurogenesis, and plasticity require changes in cytosine methylation and hydroxymethylation. Although genome-wide decreases in methylation with aging are often reported as scientific dogma, primary research reports describe decreases, increases, or lack of change in methylation and hydroxymethylation and their principle regulators, DNA methyltransferases and ten-eleven translocation dioxygenases in the hippocampus. Furthermore, existing data are limited to only male animals. RESULTS: Through examination of the hippocampus in young, adult, and old male and female mice by antibody-based, pyrosequencing, and whole-genome oxidative bisulfite sequencing methods, we provide compelling evidence that contradicts the genomic hypomethylation theory of aging. We also demonstrate that expression of DNA methyltransferases and ten-eleven translocation dioxygenases is not differentially regulated with aging or between the sexes, including the proposed cognitive aging regulator DNMT3a2. Using oxidative bisulfite sequencing that discriminates methylation from hydroxymethylation and by cytosine (CG and non-CG) context, we observe sex differences in average CG methylation and hydroxymethylation of the X chromosome, and small age-related differences in hydroxymethylation of CG island shores and shelves, and methylation of promoter regions. CONCLUSION: These findings clarify a long-standing misconception of the epigenomic response to aging and demonstrate the need for studies of base specific methylation and hydroxymethylation with aging in both sexes. PMID- 27413397 TI - Craniocervical Posture in Patients with Obstructive Sleep Apnea. AB - INTRODUCTION: Obstructive Sleep Apnea (OSA) is characterized by repeated episodes of upper airway obstruction during sleep. OBJECTIVE: The objective of this study is to verify the craniofacial characteristics and craniocervical posture of OSA and healthy subjects, determining possible relationships with the apnea/hypopnea index (AHI). METHODS: This case-control study evaluated 21 subjects with OSA, who comprised the OSA group (OSAG), and 21 healthy subjects, who constituted the control group (CG). Cephalometry analyzed head posture measurements, craniofacial measurements, and air space. Head posture was also assessed by means of photogrammetry. RESULTS: The groups were homogeneous regarding gender (12 men and 9 women in each group), age (OSAG = 41.86 +/- 11.26 years; GC = 41.19 +/- 11.20 years), and body mass index (OSAG = 25.65 +/- 2.46 kg/m2; CG = 24.72 +/- 3.01 kg/m2). We found significant differences between the groups, with lower average pharyngeal space and greater distance between the hyoid bone and the mandibular plane in OSAG, when compared with CG. A positive correlation was found between higher head hyperextension and head anteriorization, with greater severity of OSA as assessed by AHI. CONCLUSION: OSAG subjects showed changes in craniofacial morphology, with lower average pharyngeal space and greater distance from the hyoid bone to the mandibular plane, as compared with healthy subjects. Moreover, in OSA subjects, the greater the severity of OSA, the greater the head hyperextension and anteriorization. PMID- 27413398 TI - Rigid Bronchoscopy in Airway Foreign Bodies: Value of the Clinical and Radiological Signs. AB - INTRODUCTION: Foreign body in airway is a common emergency in ENT practice. As we know, Rigid Bronchoscopy is the method of choice for removing it, although at times it leads to specialists performing unnecessary bronchoscopy, exposing patients to hazards of general anesthesia. OBJECTIVE: The objective of my study is to calculate sensitivity, specificity, positive predictive value, odds ratio from the clinical and radiological signs, comparing with the gold standard, the rigid bronchoscope procedure. METHOD: This is a prospective analytical study designed at University Teaching Hospital and conducted over a period of 18 months, from March 2011 to August 2012. Data collection was broadly classified into three different categories: (1) Symptomatology, such as presence or absence of choking, cyanosis, and difficulty in breathing; (2) Clinical signs, such as the presence or absence of air entry, crackles, and rhonchi 3. Chest X-ray findings were suggestive of a foreign body. RESULTS: There were a total of 40 rigid bronchoscopies performed under general anesthesia for the diagnosis and therapeutic reasons. Among 40 patients who underwent rigid bronchoscopy, 32 (80%) were found to have varieties of foreign bodies in their airway while 8 patients (20%) had negative bronchoscopy. The history of choking is the only clinical symptoms which came out to be statistically Significant (p = 0.043) with odds ratio of 5. CONCLUSION: Rigid bronchoscopy is the gold standard technique for diagnosis and procedure of choice to remove FB from airway. Regardless, it still presents a small chance of negative result, especially when there is no history of aspiration. PMID- 27413399 TI - The Impact of Dysphagia Therapy on Quality of Life in Patients with Parkinson's Disease as Measured by the Swallowing Quality of Life Questionnaire (SWALQOL). AB - INTRODUCTION: Dysphagia is a common symptom in Parkinson's disease (PD) and it has been associated with poor quality of life (QoL), anxiety, depression. OBJECTIVE: The aim of this study was to evaluate the quality of life in individuals with PD before and after SLP therapy. METHODS: The program consisted of four individual therapy sessions. Each session comprised guidelines regarding food and postural maneuvers (chin down). The Quality of Life in Swallowing Disorders (SWAL-QOL) questionnaire was applied before and after therapy. RESULTS: The sample comprised of 10 individuals (8 men), with a mean (SD) age of 62.2 (11.3) years, mean educational attainment of 7.5 (4.3) years, and mean disease duration of 10.7 (4.7) years. Thirty percent of patients were Hoehn and Yahr (H&Y) stage 2, 50% were H&Y stage 3, and 20% were H&Y stage 4. Mean scores for all SWAL-QOL domains increased after the intervention period, with significant pre- to post-therapy differences in total score (p = 0.033) and domain 4 (symptom frequency) (p = 0.025). There was also a bias significance for domain 5 (food selection) (p = 0.095). CONCLUSION: Patients exhibited improvement in swallowing related quality of life after a SLP therapy program. The earlier in the course of PD, greater the improvement observed after therapy. PMID- 27413400 TI - Advanced Orofacial Rhabdomyosarcoma: A Retrospective Study of 31 Cases. AB - INTRODUCTION: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma encountered in childhood and adolescence. Early diagnosis of pediatric cases is critical to improving outcomes, especially when socioeconomic status and geographical access to specialist services can reduce opportunities for early cancer detection and treatment. OBJECTIVE: The objective of this study is to determine factors that can delay referral and treatment in specialist pediatric oncology center upon our population specificities. METHODS: This retrospective study involved 31 children between 2003 and 2013. Children affected by histologically confirmed RMS occurring as a primary lesion in the orofacial area were included. RESULTS: The median age was 8 +/- 4.22 years (range: 3 months - 15 years). The male to female ratio was 1.8:1. Most of the patients had advanced stage disease at presentation (81.7% group had 3-4 pretreatment staging) with parameningeal involvement in 80.6% of the cases. The 2-year event-free survival rate was 17.7 +/- 7.8% for all the patients. Delay of admission to our unit and abandonment of treatment seem to be important factors for the dismal prognosis. CONCLUSION: Patient's location, socioeconomic status and health care coverage have had an impact on longer delays in seeking care and on follow-up. More studies are needed for implementation of a better management practices and a better supportive care upon specificities of our population. PMID- 27413401 TI - Transoral CO2 Laser Microsurgery Outcomes for Early Glottic Carcinomas T1-T2. AB - INTRODUCTION: Transoral laser microsurgery (TLM) has won territory in larynx oncology, establishing itself as an effective option in treatment of glottic, supraglottic, and hypopharynx tumors. Its advantages include limited resections, a reduction in number of tracheostomies, and the use of nasogastric tubes. Moreover, its oncological benefits are similar to those from open surgery in patients with early or advanced stages, when correctly selected. OBJECTIVE: The objective of this study is to review oncologic outcomes obtained with the treatment of a series of glottic tumors, treated by TLM. METHODS: Retrospective analysis of patients previously untreated, diagnosed with squamous cell carcinoma of the glottis (T1a, T1b, T2) in a tertiary university hospital. Endpoints for analysis were local control, overall and disease-specific survival, and larynx preservation rate. RESULTS: The study group included 58 patients that met the inclusion criteria: 57 (98.3%) men and 1 (1.7%) woman. Mean age was 65.5 +/- 10.7 years (Min: 46/Max: 88). The tumor stages of the patients included were 30 T1a, 11 (19%) T1b, and 17 (29.3%) T2. Three-year overall survival rate was 89.7% (Fig. 1), and three-year disease-specific survival rate was 96.5%, three-year local control rate was 98.3%, and three-year organ preservation rate was 98.3%. CONCLUSION: TLM is a safe and effective option in the treatment of glottis carcinomas, associated with less morbidity and a high percentage of local control, overall survival, specific survival, and organ preservation. PMID- 27413402 TI - Comparison between the Reflux Finding Score and the Reflux Symptom Index in the Practice of Otorhinolaryngology. AB - INTRODUCTION: The Gastroesophageal Reflux Disease has a prevalence of ~12% of the urban population in Brazil. Koufman proposed the term to designate Laryngeal Pharyngeal Reflux (LPR) symptoms, signs or tissue damage resulting from aggression of the gastrointestinal contents in the upper aerodigestive tract. Belafsky et al proposed a score that points to inflammatory laryngeal signs through videolaryngoscopic findings, the Reflux Finding Score (RFS). Moreover, in 2002, they published the Reflux Symptom Index (RSI). OBJECTIVE: The objective of this study is to provide a comparison between the Reflux Finding Score and the Reflux Symptom Index in the practice of Otorhinolaryngology. METHODS: Our study involved a total of 135 patients who visited the Ear, Nose, and Throat (ENT) clinic Nucleo de Otorrinolaringologia e Cirurgia de Cabeca e Pescoco de Sao Paulo between April 2014 and May 2015 with suspected LPR. We excluded nine patients and the study group was 126 patients. All patients were ranked by their RSI and RFS scores. RESULTS: The study group consisted of 126 patients (88 women and 38 men). Their main complaints were cough (40.4%), globus (21.4%), dysphonia (19.8%), throat clearing (15.8%), postnasal drip (3.17%), snoring (1.5%), dysphagia (1.5%), cacosmia (0.7%), and regurgitation (1.5%). The RSI ranges from 13 to 42 with a mean of 20.7 (SD = 6.67). The RFS ranged from 3 to 19 with a mean of 9.53 (SD = 2.64). CONCLUSION: The RSI and RFS can easily be included in ENT routines as objective parameters, with low cost and high practicality. Based on the clinical index, the specialist can evaluate the need for further tests. PMID- 27413403 TI - The Effect of Propolis in Healing Injured Nasal Mucosa: An Experimental Study. AB - INTRODUCTION: Mechanical trauma to the nasal mucosa increases the risk of synechia formation, especially after chronic rhinosinusitis and nasal surgeries. OBJECTIVE: This study was carried to assess the effect of propolis administration in healing injured nasal mucosa in rats. METHODS: We randomly divided eighteen rats into three equal experimental groups: (1) non-treated group; (2) gum tragacanth (suspending agent for propolis) treated group; and (3) propolis treated group. The non-treated group received no treatment for 15 days. The second group received gum tragacanth administration (5 ml/kg, orally) once daily for 15 days. The third group received propolis suspension orally at a dose of 100 mg/kg once daily for 15 days. At the beginning of this study, we induced unilateral mechanical nasal trauma on the right nasal mucosa of all rats in the three groups using a brushing technique. A pathologist stained tissue samples using hematoxylin and examined eosin by using a light microscope. RESULTS: The severity of inflammation was milder with the absence of ulcerations in the propolis treated group compared with the non-treated and gum tragacanth groups. Goblet cell and ciliated cell loss was substantially lower in patients treated with propolis compared with groups without treatment and those treated with gum tragacanth. CONCLUSION: Propolis decreased inflammation and enhanced healing of wounds of the nasal mucosa in rats. PMID- 27413405 TI - Quality of Life and Gait in Elderly Group. AB - INTRODUCTION: The process of aging could lead to seniors being more prone to falls, which affects their quality of life. OBJECTIVE: The objective of this study is to investigate the relationship between quality of life and gait in the elderly. METHODS: We used World Health Organization Quality of Life-Brief (WHOQOL Brief) Brazilian version and the Dynamic Gait Index to assess fifty-six volunteers from the northeast of Brazil. Ages ranged from 60 to 85 years. RESULTS: The Dynamic Gait Index, which indicates the probability of falls, resulted in 36.3% of the sample presenting abnormal results. There was correlation between domain 2 (psychological) and domain 4 (environment) with domain 1(Physical) and domain 3 (Social); a negative correlation between age and Domain 2; correlation between Question 1 (How would you rate your quality of life?) and domains 1, 2, and 4 and no correlation between questions 1 and 2 (How satisfied are you with your health?). Question 2 was correlated with all of the domains. There was negative association between question 1 and falls, and a slight correlation between the Dynamic Gait Index scores and Question 1. CONCLUSION: The self-perception of the study group about their quality of life was either good or very good, even though a considerable percentage of individuals had suffered falls or reported gait disturbances. PMID- 27413404 TI - Brainstem Encoding of Aided Speech in Hearing Aid Users with Cochlear Dead Region(s). AB - INTRODUCTION: Neural encoding of speech begins with the analysis of the signal as a whole broken down into its sinusoidal components in the cochlea, which has to be conserved up to the higher auditory centers. Some of these components target the dead regions of the cochlea causing little or no excitation. Measuring aided speech-evoked auditory brainstem response elicited by speech stimuli with different spectral maxima can give insight into the brainstem encoding of aided speech with spectral maxima at these dead regions. OBJECTIVE: This research aims to study the impact of dead regions of the cochlea on speech processing at the brainstem level after a long period of hearing aid use. METHODS: This study comprised 30 ears without dead regions and 46 ears with dead regions at low, mid, or high frequencies. For all ears, we measured the aided speech-evoked auditory brainstem response using speech stimuli of low, mid, and high spectral maxima. RESULTS: Aided speech-evoked auditory brainstem response was producible in all subjects. Responses evoked by stimuli with spectral maxima at dead regions had longer latencies and smaller amplitudes when compared with the control group or the responses of other stimuli. CONCLUSION: The presence of cochlear dead regions affects brainstem encoding of speech with spectral maxima perpendicular to these regions. Brainstem neuroplasticity and the extrinsic redundancy of speech can minimize the impact of dead regions in chronic hearing aid users. PMID- 27413406 TI - Dizziness Handicap Inventory and Visual Vertigo Analog Scale in Vestibular Dysfunction. AB - INTRODUCTION: Dizziness is one of the most common symptoms among the population, producing numerous consequences for individual's quality of life. There are some questionnaires that can trace the patient's profile and quality of life impairment from dizziness, including the Dizziness Handicap Inventory (DHI) and the Visual Vertigo Analogue Scale (VVAS). OBJECTIVE: This study aims to correlate the results of the DHI and VVAS in patients with vestibular dysfunction. METHODS: This is a retrospective study of medical records of patients treated in a medical school between 2006 and 2012. Results of the DHI and EVA were collected and subjected to statistical analysis using Pearson's correlation test with p < 0.001. The significance level adopted for the statistical tests was p <= 0.05. RESULTS: A total of 91 records were included in this study, 72 (79.1%) from female and 19 (20.9%) from male patients, aged 23 to 86 years, with a mean age of 52.5 years. The mean score on the DHI total was 43.9 and 5.2 points for the EVA. The result of Pearson's correlation test was 0.54. CONCLUSION: Self-perceived dizziness measured with the Dizziness Handicap Inventory has a regular and positive correlation with the Visual Vertigo Analog Scale in patients with vestibular dysfunction. The clinical trial is registered under number UTN U1111 1170-5065. PMID- 27413407 TI - The Efficacy of Adjuvant Intratympanic Steroid Treatment for Otitis Media with Effusion in Children. AB - INTRODUCTION: Otitis media with effusion (OME) is a leading cause of hearing impairment in children. Therefore, early and proper management is essential. OBJECTIVES: The objective of this research is to assess the efficacy of intratympanic (IT) steroids injection for management of otitis media with effusion (OME). METHODS: This study involved 42 children (84 ears) with bilateral OME. We used tympanometry to confirm the childrens middle ear effusion and pure tone audiometry to determine hearing threshold. We performed myringotomy and inserted ventilation tubes (VTs) bilaterally, followed by a steroid injection of 0.4-0.6 mL methylprednisolone (40 mg/mL) into one randomly selected middle ear. This procedure was followed by once-weekly administration of steroids (0.5 mL methylprednisolone at a concentration of 40 mg/mL) into the middle ear for three consecutive weeks. RESULTS: We found recurrent OME after VT alone in nine (21.4%) ears; whereas, after VT combined with steroid administration, we found two (4.76%), with statistically significant difference. We noted tympanosclerosis postoperatively in six (12.9%) ears and in one of the injected ears (2.3%) (p = 0.0484). Otorrhea occurred in eight (19%) ears with VT alone and in three (7.1%) injected ears, with non-significant difference. The duration between VT insertion and its extrusion was 6.6 = 1.1 months for ears with VT alone and 6.95 =1.12 months in injected ears (p = 0.1541 NS). CONCLUSION: IT Steroids injection for treatment of OME is a safe and simple intervention with lower incidence of symptoms recurrence and postoperative complications. Thus, its use in management of OME is recommended. PMID- 27413408 TI - Pitch and Loudness from Tinnitus in Individuals with Noise-induced Hearing Loss. AB - INTRODUCTION: Tinnitus is one of the symptoms that affects individuals suffering from noise induced hearing loss. This condition can be disabling, leading the affected individual to turn away from work. OBJECTIVE: This literature review aims to analyze the possible association between gender and tinnitus pitch and loudness, the degree of hearing loss and the frequencies affected in subjects with noise-induced hearing loss. METHODS: This contemporary cohort study was conducted through a cross-sectional analysis. The study sample consisted of adults with unilateral or bilateral tinnitus, who had been diagnosed with noise induced hearing loss. The patients under analysis underwent an otorhinolaryngological evaluation, pure tone audiometry, and acuphenometry. RESULTS: The study included 33 subjects with noise-induced hearing loss diagnoses, of which 22 (66.7%) were men. Authors observed no statistical difference between gender and loudness/pitch tinnitus and loudness/pitch in subjects with bilateral tinnitus. Authors found an inverse relation between tinnitus loudness with intensity greater hearing threshold and the average of the thresholds and the grade of hearing loss. The tinnitus pitch showed no association with higher frequency of hearing threshold. CONCLUSION: Data analysis shows that, among the individuals evaluated, the greater the hearing loss, the lower the loudness of tinnitus. We did not observe an association between hearing loss and tinnitus pitch. PMID- 27413409 TI - Auditory Speech Perception Tests in Relation to the Coding Strategy in Cochlear Implant. AB - INTRODUCTION: The objective of the evaluation of auditory perception of cochlear implant users is to determine how the acoustic signal is processed, leading to the recognition and understanding of sound. OBJECTIVE: To investigate the differences in the process of auditory speech perception in individuals with postlingual hearing loss wearing a cochlear implant, using two different speech coding strategies, and to analyze speech perception and handicap perception in relation to the strategy used. METHODS: This study is prospective cross-sectional cohort study of a descriptive character. We selected ten cochlear implant users that were characterized by hearing threshold by the application of speech perception tests and of the Hearing Handicap Inventory for Adults. RESULTS: There was no significant difference when comparing the variables subject age, age at acquisition of hearing loss, etiology, time of hearing deprivation, time of cochlear implant use and mean hearing threshold with the cochlear implant with the shift in speech coding strategy. There was no relationship between lack of handicap perception and improvement in speech perception in both speech coding strategies used. CONCLUSION: There was no significant difference between the strategies evaluated and no relation was observed between them and the variables studied. PMID- 27413410 TI - Hearing Loss, Dizziness, and Carbohydrate Metabolism. AB - INTRODUCTION: Metabolic activity of the inner ear is very intense, and makes it sensitive to changes in the body homeostasis. This study involves a group of patients with inner ear disorders related to carbohydrate metabolism disturbances, including hearing loss, tinnitus, dizziness, and episodes of vertigo. OBJECTIVES: To describe the symptoms of metabolic inner ear disorders and the examinations required to establish diagnoses. These symptoms are often the first to allow for an early diagnosis of metabolic disorders and diabetes. METHODS: Retrospective study of 376 patients with inner ear symptoms suggestive of disturbances of carbohydrate metabolism. The authors present patients clinical symptoms and clinical evaluations, with emphasis on the glucose and insulin essays. RESULTS: Authors based their conclusions on otolaryngological findings, diagnostic procedures and treatment principles. They found that auditory and vestibular symptoms usually occur prior to other manifestations of metabolic changes, leading to an early diagnosis of hyperinsulinemia, intestinal sugar malabsorption or diabetes. Previously undiagnosed diabetes mellitus type II was found in 39 patients. CONCLUSIONS: The identification of carbohydrate metabolism disturbances is important not only to minimize the patients' clinical symptoms, but also to help maintain their general health. PMID- 27413411 TI - Minimally Invasive Surgery for Intracochlear Schwannoma Removal and Simultaneous Cochlear Implantation. AB - INTRODUCTION: Hearing preservation has not yet been reported in patients undergoing resection of intracochlear schwannomas. This study describes a minimally invasive procedure for intracochlear schwannoma resection with simultaneous cochlear implantation that resulted in good hearing. OBJECTIVE: This study aims to describe a minimally invasive procedure for intracochlear schwannoma resection with simultaneous cochlear implantation. DATA SYNTHESIS: The technique described in this study was developed for a 55-year-old male with a 20 year history of bilateral progressive hearing loss and tinnitus that had a mass in the left apical turn of the cochlea measuring 0.3 cm. Surgery accessed the apical turn of the cochlea. We performed mastoidectomy and posterior tympanotomy and removed incus and tensor tympani muscle to expose the cochlear apex. The tumor was identified and completely resected. After the cochlea was anatomically preserved, it was implanted with a straight electrode via round window insertion. The histopathological examination confirmed intracochlear schwannoma. Speech perception test revealed 100% speech recognition with closed sentences and the average audiometric threshold (500 to 2000 Hz) was 23 dB. CONCLUSION: Our technique led to rehabilitation of the patient and improved hearing without damaging the intracochlear structure, making it possible to perform CI in the same procedure with good results. PMID- 27413412 TI - Interventions in the Alteration on Lingual Frenum: Systematic Review. AB - INTRODUCTION: Altered lingual frenum modifies the normal tongue mobility, which may influence the stomatognathic functions, resulting in anatomical, physiological and social damage to the subject. It is necessary that health professionals are aware of the process of evaluation, diagnostics and treatment used today, guiding their intervention. OBJECTIVE: To perform a systematic review of what are the treatment methods used in cases of lingual frenum alteration. DATA SYNTHESIS: The literature searches were conducted in MEDLINE, LILACS, SciELO, Cochrane and IBECS, delimited by language (Portuguese, English, Spanish), date of publication (January 2000 to January 2014) and studies performed in humans. The selection order used to verify the eligibility of the studies were related to: full text availability; review the abstract; text analysis; final selection. Of the total 443 publications, 26 remained for analysis. The surgical approach was used in all studies, regardless of the study population (infants, children and adults), with a range of tools and techniques employed; speech therapy was recommended in the post surgical in 4 studies. Only 4 studies, all with infants, showed scientific evidence. CONCLUSION: Surgical intervention is effective for the remission of the limitations caused by the alteration on lingual frenum, but there is a deficit of studies with higher methodological quality. The benefits of speech therapy in the post surgical period are described from improvement in the language of mobility aspects and speech articulation. PMID- 27413413 TI - High-frequency Audiometry Hearing on Monitoring of Individuals Exposed to Occupational Noise: A Systematic Review. AB - INTRODUCTION: The literature reports on high-frequency audiometry as one of the exams used on hearing monitoring of individuals exposed to high sound pressure in their work environment, due to the methods greater sensitivity in early identification of hearing loss caused by noise. The frequencies that compose the exam are generally between 9 KHz and 20KHz, depending on the equipment. OBJECTIVE: This study aims to perform a retrospective and secondary systematic revision of publications on high-frequency audiometry on hearing monitoring of individuals exposed to occupational noise. DATA SYNTHESIS: This systematic revision followed the methodology proposed in the Cochrane Handbook, focusing on the question: "Is High-frequency Audiometry more sensitive than Conventional Audiometry in the screening of early hearing loss individuals exposed to occupational noise?" The search was based on PubMed data, Base, Web of Science (Capes), Biblioteca Virtual em Saude (BVS), and in the references cited in identified and selected articles. The search resulted in 6059 articles in total. Of these, only six studies were compatible with the criteria proposed in this study. CONCLUSION: The performed meta-analysis does not definitively answer the study's proposed question. It indicates that the 16 KHz high frequency audiometry (HFA) frequency is sensitive in early identification of hearing loss in the control group (medium difference (MD = 8.33)), as well as the 4 KHz frequency (CA), this one being a little less expressive (MD = 5.72). Thus, others studies are necessary to confirm the HFA importance for the early screening of hearing loss on individuals exposed to noise at the workplace. PMID- 27413415 TI - A novel deleterious c.2656G>T MSH2 germline mutation in a Pakistani family with a phenotypic overlap of hereditary breast and ovarian cancer and Lynch syndrome. AB - BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS) account for a significant proportion of inherited gynecologic malignancies, mainly caused by pathogenic germline mutations in the BRCA1 and BRCA2 genes or in mismatch repair (MMR) genes, such as MLH1 and MSH2. Women harboring deleterious mutations in these genes have increased life-time risks of developing a number of malignancies including ovarian cancer. Since there is a phenotypic overlap of HBOC and LS, timely identification of individuals at-risk of a particular syndrome is crucial in order to optimize cancer risk management. CASE PRESENTATION: We report a novel pathogenic MSH2 mutation, c.2656G > T, which was identified in a 67-year-old female patient with breast cancer, who had previously tested negative for a deleterious mutation in the breast cancer susceptibility genes BRCA1, BRCA2, CHEK2 or RAD51C. The patient reported a personal history of endometrial cancer diagnosed at age 48, and a strong family history of breast and ovarian cancer, as well as several other malignancies within the spectrum of LS. The novel mutation was also found in the index patient's daughter and a niece, who were diagnosed with endometrial and ovarian cancer, respectively. Breast and endometrial tumors from c.2656G > T mutation carriers showed loss of MSH2 and MSH6 protein expression. The mutation was absent in the control population. CONCLUSIONS: Our finding suggests that testing for MMR genes may be of benefit to BRCA1/2 negative families with overlapping HBOC and LS phenotype in Pakistan. It is clinically significant to identify individuals harboring mutations in genes linked with a particular syndrome so that they can benefit from targeted life-saving cancer surveillance and preventive strategies. PMID- 27413416 TI - Developing Community-Level Policy and Practice to Reduce Traffic-Related Air Pollution Exposure. AB - The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic-related pollutants (TRAP) are elevated within 200 400 m of these roads. Community-level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near-highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning. PMID- 27413414 TI - Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine. AB - In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown. PMID- 27413417 TI - Effects of Synthetic Serum Supplementation in Sperm Preparation Media on Sperm Capacitation and Function Test Results. AB - Albumin supplementation of culture media induces sperm capacitation in assisted reproduction technique cycles. Synthetic serum supplementation is clinically used to replace albumin for preventing transmission of infectious agents. However, the effects of synthetic serum supplementation on sperm capacitation have rarely been investigated. Spermatozoa from 30 men with normal basic semen analysis results were collected, divided into five aliquots, and cultured in capacitating conditions in four combinations of two synthetic serum supplements, serum substitute supplement (SSS) and serum protein substitute (SPS), and two fertilization media, Quinns AdvantageTM Fertilization (QF) and human tubular fluid (HTF) media. Reactive oxygen species (ROS) levels in spermatozoa were measured through chemiluminescence. Furthermore, acrosome reaction and western blotting for tyrosine phosphorylation were used to evaluate sperm capacitation. HTF+SSS had significantly higher ROS levels than QF+SPS did (11,725 +/- 1,172 versus 6,278 +/- 864 relative light units). In addition, the spermatozoa cultured in QF+SPS had lower motility, acrosome reaction rates, and tyrosine phosphorylation levels compared with those cultured in HTF+SSS. In conclusion, the effects of synthetic serum supplementation on sperm capacitation varied according to the combination of media. These differences may lead to variations in spermatozoon ROS levels, thus affecting sperm function test results. PMID- 27413418 TI - Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice. AB - Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-alpha, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury. PMID- 27413419 TI - Effects of Oxidative Stress on Mesenchymal Stem Cell Biology. AB - Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. PMID- 27413421 TI - Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis. AB - Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis. PMID- 27413420 TI - Biological Activities of 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-Glucoside in Antiaging and Antiaging-Related Disease Treatments. AB - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) is active component of the Chinese medicinal plant Polygonum multiflorum Thunb. (THSG). Pharmacological studies have demonstrated that THSG exhibits numerous biological functions in treating atherosclerosis, lipid metabolism, vascular and cardiac remodeling, vascular fibrosis, cardiac-cerebral ischemia, learning and memory disorders, neuroinflammation, Alzheimer and Parkinson diseases, diabetic complications, hair growth problems, and numerous other conditions. This review focuses on the biological effects of THSG in antiaging and antiaging-related disease treatments and discusses its molecular mechanisms. PMID- 27413422 TI - In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice. AB - This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (alpha-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) alpha-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) alpha-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and alpha-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5. PMID- 27413425 TI - The Literature Review: A Foundation for High-Quality Medical Education Research. PMID- 27413426 TI - Repairing the Residency Application Process. PMID- 27413424 TI - Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response. AB - Rituximab has been revolutionized and validated CD20 targeting monoclonal antibody. Although, it is widely used for lymphoma therapy and many patients have been benefited. However significant numbers of patients are refractory or developed resistance to current therapies due to low level of CD20 expression and/or availability on cells surface. Thus development of novel anti-CD20 mAbs with great cell killing ability and enhance CD20 levels on cell surface can potentially exploit lymphoma therapy. In this scenario, we are summarizing the recently developed mAbs against CD20 and compounds that have ability to induce CD20 expression at significant level. We also are providing information regarding combination strategy for use of radiation and anti-CD20 mAbs in vitro. However, it will need to be determined by rigorous at pre-clinical and clinic testing. We hope this review will be beneficial for current research in the area of immunotherapy or radio-immunotherapy. PMID- 27413427 TI - Viewpoint From 2 Undergraduate Medical Education Deans The Residency Application Process: Working Well, Needs Fixing, or Broken Beyond Repair? PMID- 27413423 TI - Physiological Importance of Hydrogen Sulfide: Emerging Potent Neuroprotector and Neuromodulator. AB - Hydrogen sulfide (H2S) is an emerging neuromodulator that is considered to be a gasotransmitter similar to nitrogen oxide (NO) and carbon monoxide (CO). H2S exerts universal cytoprotective effects and acts as a defense mechanism in organisms ranging from bacteria to mammals. It is produced by the enzymes cystathionine beta-synthase (CBS), cystathionine Upsilon-lyase (CSE), 3 mercaptopyruvate sulfurtransferase (MST), and D-amino acid oxidase (DAO), which are also involved in tissue-specific biochemical pathways for H2S production in the human body. H2S exerts a wide range of pathological and physiological functions in the human body, from endocrine system and cellular longevity to hepatic protection and kidney function. Previous studies have shown that H2S plays important roles in peripheral nerve regeneration and degeneration and has significant value during Schwann cell dedifferentiation and proliferation but it is also associated with axonal degradation and the remyelination of Schwann cells. To date, physiological and toxic levels of H2S in the human body remain unclear and most of the mechanisms of action underlying the effects of H2S have yet to be fully elucidated. The primary purpose of this review was to provide an overview of the role of H2S in the human body and to describe its beneficial effects. PMID- 27413428 TI - Viewpoint From a Former Medical Student/Now Intern Playing the Game-Balancing Numbers and Intangibles in the Orthopedic Surgery Match. PMID- 27413429 TI - Viewpoint From a Program Director They Can't All Walk on Water. PMID- 27413430 TI - Viewpoint From 2 Graduate Medical Education Deans Application Overload in the Residency Match Process. PMID- 27413431 TI - Residency Interviews in the 21st Century. PMID- 27413432 TI - The Electronic Health Record and Education: Rethinking Optimization. PMID- 27413433 TI - Blueprint for a Successful Resident Quality and Safety Council. PMID- 27413435 TI - Mind the Gap: Representation of Medical Education in Cardiology-Related Articles and Journals. AB - BACKGROUND: Cardiology fellowship programs are at the interface of medical education and the care of patients suffering from the leading cause of mortality in the United States, yet there is an apparent lack of research guiding the effective education of fellows. OBJECTIVE: We sought to quantify the number of publications in cardiology journals that pertained to the education of cardiology trainees and the number of cardiologists participating in education research. METHODS: For the period between January and December 2012, we cataloged cardiology-specific and general medical/medical education journals and sorted them by impact factor. Tables of content were reviewed for articles with an educational focus, a cardiology focus, or both. We recorded the authors' areas of medical training, and keywords from each cardiology journal's mission statement were reviewed for emphasis on education. RESULTS: Twenty-six cardiology journals, containing 6645 articles, were reviewed. Only 4 articles had education themes. Ten general medical and 15 medical education journals contained 6810 articles. Of these, only 7 focused on medical education in cardiology, and none focused on cardiology fellowship training. Among the 4887 authors of publications in medical education journals, 25 were cardiologists (less than 1%), and among the 1036 total words in the mission statements of all cardiology journals, the term "education" appeared once. CONCLUSIONS: Published educational research is lacking in cardiology training, and few cardiologists appear to be active members of the education scholarship community. Cardiology organizations and academic journals should support efforts to identify target areas of study and publish scholarship in educational innovation. PMID- 27413434 TI - Assessing Team Leadership in Emergency Medicine: The Milestones and Beyond. AB - BACKGROUND: Team leadership is a critical skill for emergency medicine physicians that directly affects team performance and the quality of patient care. There exists a robust body of team science research supporting team leadership conceptual models and behavioral skill sets. However, to date, this work has not been widely incorporated into health care team leadership education. OBJECTIVE: This narrative review has 3 aims: (1) to synthesize the team science literature and to translate important concepts and models to health care team leadership; (2) to describe how team leadership is currently represented in the health care literature and in the Accreditation Council for Graduate Medical Education Milestones for emergency medicine; and (3) to propose a novel, evidence-based framework for the assessment of team leadership in emergency medicine. METHODS: We conducted a narrative review of the team science and health care literature. We summarized our findings and identified a list of team leadership behaviors that were then used to create a framework for team leadership assessment. RESULTS: Current health care team leadership measurement tools do not incorporate evidence-based models of leadership concepts from other established domains. The emergency medicine milestones include several team leadership behaviors as part of a larger resident evaluation program. However, they do not offer a comprehensive or cohesive representation of the team leadership construct. CONCLUSIONS: Despite the importance of team leadership to patient care, there is no standardized approach to team leadership assessment in emergency medicine. Based on the results of our review, we propose a novel team leadership assessment framework that is supported by the team science literature. PMID- 27413436 TI - Developing a Tool to Assess Placement of Central Venous Catheters in Pediatrics Patients. AB - BACKGROUND: Pediatric critical care medicine requires the acquisition of procedural skills, but to date no criteria exist for assessing trainee competence in central venous catheter (CVC) insertion. OBJECTIVE: The goal of this study was to create and demonstrate validity evidence for a direct observation tool for assessing CVC insertion. METHODS: Ten experts used the modified Delphi technique to create a 15-item direct observation tool to assess 5 scripted and filmed simulated scenarios of CVC placement. The scenarios were hosted on a dedicated website from March to May 2013, and respondents recruited by e-mail completed the observation tool in real time while watching the scenarios. The goal was to obtain 50 respondents and a total of 250 scenario ratings. RESULTS: A total of 49 pediatrics intensive care faculty physicians (6.3% of 780 potential subjects) responded and generated 188 scenario observations. Of these, 150 (79.8%) were recorded from participants who scored 4 or more on the 5 scenarios. The tool correctly identified the expected reference standard in 96.8% of assessments with an interrater agreement kappa (standard error) = 0.94 (0.07) and receiver operating characteristic = 0.97 (95% CI 0.94-0.99). CONCLUSIONS: This direct observation assessment tool for central venous catheterization demonstrates excellent performance in identifying the reference standard with a high degree of interrater reliability. These assessments support a validity construct for a pediatric critical care medicine faculty member to assess a provider placing a CVC in a pediatrics patient. PMID- 27413437 TI - CREOG In-Training Examination Results: Contemporary Use to Predict ABOG Written Examination Outcomes. AB - BACKGROUND: The in-training examination (ITE) offers formative assessments of residents' developing medical knowledge. Identification of an ITE performance level associated with success on the specialty board examination allows identification of "at risk" residents. OBJECTIVE: This study sought to identify a threshold score for obstetrics and gynecology residents' performance on the Council on Resident Education in Obstetrics and Gynecology (CREOG) ITE that predicts successful performance on the American Board of Obstetrics and Gynecology (ABOG) written examination. METHODS: We analyzed ITE and ABOG results of 80 residents who completed 4 years of CREOG ITEs at 2 institutions between 2002 and 2012. We assessed the level of performance associated with successful performance on the ABOG written examination. RESULTS: Data analyzed included scores for 71 of 80 residents (89%), with an overall pass rate of 82%. A postgraduate year (PGY) 4 score of 200 on the CREOG ITE or twice in any of the PGY training years was associated with a 100% ABOG pass rate. Scoring >= 205 in any PGY also was associated with a 100% pass rate. Residents who did not attain a score of 200 had a 35% to 45% chance of failing the ABOG written examination, depending on the PGY of the ITE performance. CONCLUSIONS: Our findings suggest that a CREOG ITE score of at least 200 twice, or as a PGY-4, offers assurance of successful performance on the ABOG examination. Scores lower than this threshold may be used to identify "at risk" residents for added learning and provide program elements in need of improvement. PMID- 27413438 TI - The Use of COMLEX-USA and USMLE for Residency Applicant Selection. AB - BACKGROUND: The Comprehensive Osteopathic Medical Licensing Examination (COMLEX USA) and the United States Medical Licensing Examination (USMLE) are recognized by all state medical licensing boards in the United States, and the Federation of State Medical Boards has supported the validity of both examinations for medical licensure. Many osteopathic medical students take both examinations. OBJECTIVE: The purpose of this study was to investigate performance on COMLEX-USA Level 1 and USMLE Step 1 of students from colleges of osteopathic medicine where the majority of students took both examinations. METHODS: Data were collected on the entering classes of 2010 and 2011. Relationships between the COMLEX-USA Level 1 and the USMLE Step 1 were quantified using Pearson correlations. The correlation between outcomes on the 2 examinations was evaluated using the phi coefficient. A contingency table was constructed to look at first-attempt outcomes (pass/fail). RESULTS: Data for 2010 and 2011 were collected from 3 osteopathic medical schools, with 795 of 914 students (87%) taking both examinations. The correlation between first-attempt COMLEX-USA Level 1 and USMLE Step 1 scores was statistically significant across and within all 3 schools. The overall correlation was r(795) = 0.84 (P < .001). Pass/fail status on the 2 examinations was moderately correlated (phi = 0.39, P < .01). CONCLUSIONS: Our study found a strong association between COMLEX Level 1 and USMLE Step 1 performance. Additional studies to accurately compare scores on these examinations are warranted. PMID- 27413439 TI - Examining Residents' Strategic Mindfulness During Self-Regulated Learning of a Simulated Procedural Skill. AB - BACKGROUND: Simulation-based training is currently embedded in most health professions education curricula. Without evidence for how trainees think about their simulation-based learning, some training techniques may not support trainees' learning strategies. OBJECTIVE: This study explored how residents think about and self-regulate learning during a lumbar puncture (LP) training session using a simulator. METHODS: In 2010, 20 of 45 postgraduate year 1 internal medicine residents attended a mandatory procedural skills training boot camp. Independently, residents practiced the entire LP skill on a part-task trainer using a clinical LP tray and proper sterile technique. We interviewed participants regarding how they thought about and monitored their learning processes, and then we conducted a thematic analysis of the interview data. RESULTS: The analysis suggested that participants considered what they could and could not learn from the simulator; they developed their self-confidence by familiarizing themselves with the LP equipment and repeating the LP algorithmic steps. Participants articulated an idiosyncratic model of learning they used to interpret the challenges and successes they experienced. Participants reported focusing on obtaining cerebrospinal fluid and memorizing the "routine" version of the LP procedure. They did not report much thinking about their learning strategies (eg, self-questioning). CONCLUSIONS: During simulation-based training, residents described assigning greater weight to achieving procedural outcomes and tended to think that the simulated task provided them with routine, generalizable skills. Over this typical 1-hour session, trainees did not appear to consider their strategic mindfulness (ie, awareness and use of learning strategies). PMID- 27413440 TI - The Effect of Paging Reminders on Fellowship Conference Attendance: A Multi Program Randomized Crossover Study. AB - BACKGROUND: Educational conferences have long served as a foundation of medical education. Sending reminder text pages prior to the start of conferences is a method that may be employed to enhance conference attendance. OBJECTIVE: The goal of our study was to determine if routine text paging before regularly scheduled conferences improves attendance among fellows in 3 internal medicine programs. METHODS: A prospective, randomized, crossover study included 3 fellowship programs: pulmonary and critical care, cardiovascular disease, and hematology oncology. The study was performed between October 2014 and March 2015. All fellows were included and randomized to 1 of 2 groups (with subsequent crossover to opposite group): Pages or No Pages. Paging reminders, which included conference title, location, and time, were sent 30 minutes prior to every conference for those in the intervention arm. Attendance was collected through a standard attendance log using self-registration. RESULTS: A total of 46 fellows and 156 conferences were included for analysis, with 75 during the first 3 months and 81 during the second 3 months. There were no differences in individual overall attendance between randomized groups for the entire study period (42.9% versus 46.5%, P = .46). Paging reminders had no effect on overall individual attendance (43.7% versus 45.6%, P = .50). In addition, no significant differences were identified for individuals within each fellowship and training year. CONCLUSIONS: Paging reminders prior to a regularly scheduled conference had no effect on overall attendance in this study. Fellows reported that clinical obligations were a major barrier to conference attendance. PMID- 27413441 TI - A Values Affirmation Intervention to Improve Female Residents' Surgical Performance. AB - BACKGROUND: Female residents in surgical training may face stereotype threat. The awareness of negative stereotypes about surgical ability based on gender may heighten stress and thus reduce performance. OBJECTIVE: The main objective of this study was to assess the effectiveness of a brief stress-reducing writing exercise, known as a values affirmation, to mitigate the negative effects of stereotype threat on the performance of female surgical residents. METHODS: This is a randomized, controlled trial in which 167 residents were invited to participate. A total of 45 resident volunteers, including 18 women, were randomized to the affirmation condition or the no-affirmation condition. We administered a values affirmation intervention and measured clinical evaluations data both prior to and 6 months after the intervention. RESULTS: Women benefited from the affirmation. Women who had participated in the affirmation exercise earned higher clinical evaluation scores than those in the control condition (B = 0.34, P < .05). For men, performance did not differ by affirmation condition (B = -0.20, P = .35). CONCLUSIONS: Our findings suggest a benefit of values affirmation for women in surgical training, as measured by performance on clinical evaluations. This suggests that a brief psychological intervention may improve on-the-job performance for women in surgery, an underrepresented group. PMID- 27413442 TI - Facilitating Institutional Oversight and Program Improvement Through Educational Competency Committees. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires programs to engage annually in program evaluation and improvement. OBJECTIVE: We assessed the value of creating educational competency committees (ECCs) that use successful elements of 2 established processes-institutional special reviews and institutional oversight of annual program evaluations. METHODS: The ECCs used a template to review programs' annual program evaluations. Results were aggregated into an institutional dashboard. We calculated the costs, sensitivity, specificity, and predictive value by comparing programs required to have a special review with those that had ACGME citations, requests for a progress report, or a data-prompted site visit. We assessed the value for professional development through a participant survey. RESULTS: Thirty-two ECCs involving more than 100 individuals reviewed 237 annual program evaluations over a 3-year period. The ECCs required less time than internal reviews. The ECCs rated 2 to 8 programs (2.4%-9.8%) as "noncompliant." One to 13 programs (1.2% 14.6%) had opportunities for improvement identified. Institutional improvements were recognized using the dashboard. Zero to 13 programs (0%-16%) were required to have special reviews. The sensitivity of the decision to have a special review was 83% to 100%; specificity was 89% to 93%; and negative predictive value was 99% to 100%. The total cost was $280 per program. Of the ECC members, 86% to 95% reported their participation enhanced their professional development, and 60% to 95% believed the ECC benefited their program. CONCLUSIONS: Educational competency committees facilitated the identification of institution-wide needs, highlighted innovation and best practices, and enhanced professional development. The cost, sensitivity, specificity, and predictive value indicated good value. PMID- 27413443 TI - Improving Residents' Safe Opioid Prescribing for Chronic Pain Using an Objective Structured Clinical Examination. AB - BACKGROUND: Internal medicine residents care for a sizable number of patients with chronic pain. Programs need educational strategies to promote safe opioid prescribing. OBJECTIVE: To describe a safe opioid prescribing education program utilizing an objective structured clinical examination (OSCE) and report the resulting impact on residents' knowledge, confidence, and self-reported practices. METHODS: Using a quasi-experimental design, 39 internal medicine residents from an urban academic medical center were assigned to 1 of 4 groups: 1 hour lecture only, lecture followed by immediate OSCE, lecture followed by 4 month delayed OSCE, and control. Safe opioid prescribing knowledge, confidence, and self-reported practices were assessed at baseline and at 8 months. RESULTS: At 8 months, knowledge, confidence, and self-reported practices improved in the control and in all 3 intervention groups. The immediate OSCE group had the greatest improvements in combined confidence scores within group (0.74, P = .01) compared to controls (0.52, P = .05), using a 5-point scale. This group also had the greatest improvement in self-reported practice changes (1.04, P = .04), while other groups showed nonsignificant improvements-delayed OSCE (0.43, P = .44), lecture only (0.66, P = .24), and control (0.43, P = .19). CONCLUSIONS: Safe opioid prescribing education that includes a lecture immediately followed by an OSCE had an impact on residents' confidence and self-reported practices greater than those for delayed OSCE or lecture only groups. There was no difference in knowledge improvement among the groups. Lecture followed by an OSCE was highly regarded by residents, but required additional resources. PMID- 27413444 TI - Effectiveness of an Interprofessional and Multidisciplinary Musculoskeletal Training Program. AB - BACKGROUND: Musculoskeletal (MSK) problems are common, and a recent US Bone and Joint Initiative calls for new models of education and professional collaboration. Evidence of feasibility and acceptability of innovative methods are needed. OBJECTIVE: We assessed if an experimental immersion interdisciplinary MSK curriculum would be acceptable to residents from different specialties, be feasible within existing rotations, and be effective in strengthening clinical skills. METHODS: Through funding from the Veterans Affairs Office of Academic Affiliations and the Office of Specialty Care, we developed a Center of Excellence in MSK Care and Education. A core element is the monthly MSK Education Week, which teaches skills and provides opportunities to apply these in clinical settings. Participants include internal medicine, physical medicine and rehabilitation, and orthopaedic surgery residents, as well as students and residents from other health professions programs. All were assigned to the MSK week in lieu of other clinical experiences. Faculty encompassed primary care, rheumatology, endocrinology, orthopaedics, and physical medicine and rehabilitation. Assessments include surveys and a 2-station objective structured clinical examination (OSCE). RESULTS: Since 2012, a total of 176 trainees have participated. Percentage of trainees reporting ability to evaluate and manage MSK complaints increased (9% to 87% for shoulder; 18% to 86% for knee), and confidence performing MSK injections increased from 10% to 70%. Competency in evaluation of shoulder and knee pain was confirmed by OSCEs. CONCLUSIONS: The MSK week program was accepted by residents from the 3 specialties, with learners reporting improved ability to perform shoulder and knee examinations, as demonstrated by OSCEs. PMID- 27413445 TI - Integrating a Resident-Driven Longitudinal Quality Improvement Curriculum Within an Ambulatory Block Schedule. AB - BACKGROUND: Quality improvement (QI) is essential in clinical practice, requiring effective teaching in residency. Barriers include lack of structure, mentorship, and time. OBJECTIVE: To develop a longitudinal QI curriculum for an internal medicine residency program with limited faculty resources and evaluate its effectiveness. METHODS: All medicine residents were provided with dedicated research time every 8 weeks during their ambulatory blocks. Groups of 3 to 5 residents across all postgraduate year levels were formed. Two faculty members and 1 chief resident advised all groups, meeting with each group every 8 weeks, with concrete expectations for each meeting. Residents were required to complete didactic modules from the Institute for Healthcare Improvement. Current residents and alumni were surveyed for feedback. RESULTS: Over 3 years, all eligible residents (92 residents per year in 2012-2014, 102 in 2014-2015) participated in the curriculum. Residents worked on 54 quality assessment and 18 QI projects, with 6 QI projects showing statistically significant indicator improvements. About 50 mentoring hours per year were contributed by 2 faculty advisors and a chief resident. No other staff or IT support was needed. A total of 69 posters/abstracts were produced, with 13 projects presented at national or regional conferences. Survey respondents found the program useful; most (75% residents, 63% alumni) reported it changed their practice, and 71% of alumni found it useful after residency. CONCLUSIONS: Our longitudinal QI curriculum requires minimal faculty time and resulted in increased QI-related publications and measurable improvements in quality indicators. Alumni reported a positive effect on practice after graduation. PMID- 27413446 TI - Mini Surgical Simulation, Role Play, and Group and Behavioral Interviews in Resident Selection. AB - BACKGROUND: A robust selection process is critical to residents' "cultural fit" and success in their program. Traditional selection methods have shortcomings. OBJECTIVE: We describe a novel residency interview process for obstetrics gynecology residents that incorporates behavioral, group, and surgical simulation multiple mini interviews (MMIs). METHODS: In 2010, the Cedars-Sinai Medical Center obstetrics-gynecology residency program developed surgical simulation, role play, ethics group interview, and Accreditation Council for Graduate Medical Education competency-based behavioral interview stations. RESULTS: From 2010 to 2012, a total of 199 applicants were interviewed, 62 ranked in the top 20, and 18 matched into the program. The MMI scores for interview stations were used in compiling our rank list and were found to adequately differentiate candidates. The MMI mean scores for role play, ethics interview, surgical simulation, and the behavioral interview for the top 20 ranked candidates were statistically significantly higher than those for other applicants. Standardized tests minimally correlated with various interview modalities. Applicants found the interview process acceptable. Implementing these MMI stations increased the total applicant interview time for the day by 15% (from 5.5 to 6.5 hours) and increased the face-to-face interview time from 2 to 4 hours. Approximately 42 hours of coordinator time was required for the yearly interview cycle. CONCLUSIONS: A multifaceted interview process utilizing MMI, group interview, and surgical simulation MMI is feasible and acceptable. The approach may decrease subjectivity and reliance on traditional interview methods and facilitate the selection of "compatible" residents into the program. PMID- 27413447 TI - Use of Cognitive Simulation During Anesthesiology Resident Applicant Interviews to Assess Higher-Order Thinking. AB - BACKGROUND: It is difficult to assess applicants' higher-order cognitive thinking skills during conventional resident interviews. Application metrics currently employed are useful indicators of academic and personal success in targeted areas, yet value of this information in predicting future clinical performance is limited. OBJECTIVE: We developed an assessment tool to evaluate higher-order cognitive function in real time during anesthesiology resident applicant interviews. METHODS: During the 2014-2015 residency interview season, we integrated simulation training into applicant interviews to evaluate higher-order cognitive skills. Our 5-minute simulation emphasized the Team STEPPS 2-Challenge Rule and explored candidates' critical thinking, analytical decision making, and response to stress. Participating applicants were evaluated using an outcomes based checklist targeting desired responses. We also sent applicants a post National Resident Matching Program survey to assess their perceptions of the simulation's value and educational utility. RESULTS: A total of 90 applicants (75% of all applicants) participated in the simulation, which taught residents about important patient safety concepts and provided the program with real time information about their critical thinking ability. All applicants were confident or very confident that they would both speak up and know what to say if they encountered a patient safety breach as a result of participating in this exercise. Simulation performance affected desirability status for 35% of participating applicants, where 23% of applicants ranked higher, and 12% ranked lower compared to baseline application status. CONCLUSIONS: Cognitive simulation training was useful in assessing resident applicant higher-order thinking skills and in helping stratify candidates in conjunction with standard application metrics. PMID- 27413448 TI - Skills for Interviewing Adolescent Patients: Sustainability of Structured Feedback in Undergraduate Education on Performance in Residency. AB - BACKGROUND: Effective adolescent (10 to 19 years) interviewing by physicians is an essential skill that many trainees can find challenging. OBJECTIVE: We assessed whether structured adolescent interviewing using standardized patients (SPs) and feedback in undergraduate medical education (UME) has a sustained effect on residents' skills. METHODS: Postgraduate year (PGY) 1 residents conducted interviews with a SP adolescent-mother pair. The SPs independently scored each PGY-1 interview using the structured communication adolescent guide (SCAG). Unpaired t tests were conducted comparing "Total-Item" and "Global" scores of PGY-1s who received structured SP adolescent interviewing with feedback in UME ("structured training" group) to those who had not ("no structured training" group). RESULTS: PGY-1s in the structured training group (n = 23) received significantly higher mean Total-Item scores from both the SP adolescent (40.78 +/- 7.04 and 32.41 +/- 10.12, respectively; P = .001) and the SP mother (40.48 +/- 7.90 and 33.34 +/- 10.90, respectively; P = .01) than those without structured training (n = 29). Statistically significant results favoring PGY-1s with prior training were also seen with the SP adolescent and mother total Global SCAG scores. CONCLUSIONS: Structured training in adolescent interviewing with SPs and feedback in UME appears to have a sustained effect on residents' adolescent interviewing skills. PGY-1s will interview adolescents and may benefit from structured adolescent SP interviewing with feedback, especially individuals who did not have this experience during their medical school training. PMID- 27413449 TI - Trends in High-Value Care as Reported by Internal Medicine Program Directors. AB - BACKGROUND: The value of care, defined as the relationship of cost, harm, and benefit, has garnered increased focus in recent years. Program directors (PDs) can provide information about resident skill and institutional priorities related to high-value care. OBJECTIVE: The objective of the study was to evaluate changes between 2012 and 2014 in PD-reported resident skills and institutional priorities related to high-value care. METHODS: We performed annual surveys of US internal medicine PDs from 2012-2014 and evaluated responses to identical questions related to high care value. The survey was developed by the American College of Physicians and the Alliance for Academic Internal Medicine. RESULTS: Response rates were 235 of 378 (62.2%) in 2012, 213 of 380 (56.1%) in 2013, and 215 of 391 (54.9%) in 2014. The majority of PDs reported that balancing benefits, harms, and costs was (1) a teaching priority; (2) the subject of didactics; (3) discussed by residents; and (4) emphasized by institutional leadership. Approximately one third reported that unnecessary ordering occurred most or all the time, with no changes in the survey period. When asked about resident ordering compared to 3 years ago, 42.5% (88 of 207) of PDs reported residents ordering fewer unnecessary tests most or all the time in 2014, compared to 28.1% (63 of 224) in 2012 (P = .002). CONCLUSIONS: Internal medicine PDs reported high levels of institutional interest in and teaching of care value between 2012 and 2014, but responses for later years suggest improvement in trainees avoiding unnecessary testing. PMID- 27413451 TI - Podcasts: Accessing, Choosing, Creating, and Disseminating Content. PMID- 27413450 TI - Mapping Direct Observations From Objective Structured Clinical Examinations to the Milestones Across Specialties. AB - BACKGROUND: Little is known about residents' performance on the milestones at the institutional level. Our institution formed a work group to explore this using an institutional-level curriculum and residents' evaluation of the milestones. OBJECTIVE: We assessed whether beginner-level milestones for interpersonal and communication skills (ICS) related to observable behaviors in ICS-focused objective structured clinical examinations (OSCEs) for postgraduate year (PGY) 1 residents across specialties. METHODS: The work group compared ICS subcompetencies across 12 programs to identify common beginner-level physician patient communication milestones. The selected ICS milestone sets were compared for common language with the ICS-OSCE assessment tool-the Kalamazoo Essential Elements of Communication Checklist-Adapted (KEECC-A). To assess whether OSCE scores related to ICS milestone scores, all PGY-1 residents from programs that were part of Next Accreditation System Phase 1 were identified; their OSCE scores from July 2013 to June 2014 and ICS subcompetency scores from December 2014 were compared. RESULTS: The milestones for 10 specialties and the transitional year had at least 1 ICS subcompetency that related to physician-patient communication. The language of the ICS beginner-level milestones appears similar to behaviors outlined in the KEECC-A. All 60 residents with complete data received at least a beginner-level ICS subcompetency score and at least a satisfactory score on all 3 OSCEs. CONCLUSIONS: The ICS-OSCE scores for PGY-1 residents appear to relate to beginner-level milestones for physician-patient communication across multiple specialties. PMID- 27413452 TI - Integrating Theory Into Qualitative Medical Education Research. PMID- 27413453 TI - Can a Brief Values Affirmation Help Achieve Gender Parity Within the Surgical Profession? The Promise and Limitations of "Wise" Interventions. PMID- 27413454 TI - Assessment and the Competencies: A Faculty Development Game. PMID- 27413455 TI - "Teaching Tokens" to Enhance Residents-as-Teachers Curriculum: Pilot Intervention to Improve Clinical Efficiency. PMID- 27413456 TI - WIREd for Milestones. PMID- 27413457 TI - Reducing Errors in Reporting Scholarly Activity to the ACGME: The Annual Update Scholarly Activity Monitoring Tool. PMID- 27413458 TI - Multidisciplinary Thyroid Biopsy Clinic at the University of Vermont-A Comprehensive Educational Experience. PMID- 27413459 TI - An Intervention to Teach Physicians to Use Plain Language for After Visit Summaries. PMID- 27413460 TI - SMART: A Program to Enhance Self-Directed Learning. PMID- 27413461 TI - Novel Observational Tools to Assess Residents' Performance in Patient Education. PMID- 27413462 TI - Demystifying Spiritual Care: An Interprofessional Approach for Teaching Residents and Hospital Chaplains to Work Together. PMID- 27413463 TI - Rounds for Reflection (R4R): Enhancing the Physician-Patient Connection Through Storytelling. PMID- 27413465 TI - Get a "CLEW": Using Clinical Learning Environment Walks (CLEWs) to Optimize Clinical Learning Environments. PMID- 27413464 TI - Operation La Sierra: A Novel Wellness Initiative for Neurological Surgery Residents. PMID- 27413466 TI - Early Engagement of Residents Into the Root Cause Analysis Process. PMID- 27413467 TI - QI-on-the-Fly: Continuous Faculty Development to Enhance Patient Safety Teaching and Reporting. PMID- 27413468 TI - Ethics M&Ms: Toward a Recognition of Ethics in Everyday Practice. PMID- 27413469 TI - New Rules for Postinterview Communications Between Applicants and Residency Programs? PMID- 27413470 TI - Bring Back the Interview for Exiting Medical Students in the United Kingdom. PMID- 27413471 TI - ERAS: Can It Be Revamped? One Point of View. PMID- 27413472 TI - Integrating Outpatient Teledermatology Education Into the Dermatology Resident Curriculum. PMID- 27413473 TI - Reflections on the ACGME CLER Survey. PMID- 27413474 TI - Jarring Unprofessionalism: Argot Revisited. PMID- 27413475 TI - The Journey to ACGME Accreditation: A Program's Perspectives and Practical Guidance From the ACGME. PMID- 27413476 TI - Early Impressions of the CLER Program: A Survey of the Designated Institutional Official Community. PMID- 27413477 TI - Deep brain stimulation versus motor cortex stimulation for neuropathic pain: A minireview of the literature and proposal for future research. AB - The treatment of neuropathic pain remains a public health concern. A growing cohort of patients is plagued by medically refractory, unrelenting severe neuropathic pain that ruins their quality of life and productivity. For this group, neurosurgery can offer two different kinds of neuromodulation that may help: deep brain simulation (DBS) and motor cortex stimulation (MCS). Unfortunately, there is no consensus on how to perform these procedures, which stimulation parameters to select, how to measure success, and which patients may benefit. This brief review highlights the literature supporting each technique and attempts to provide some comparisons and contrasts between DBS and MCS for the treatment of neuropathic pain. Finally, we highlight the current unanswered questions in the field and suggest future research strategies that may advance the care of our patients with neuropathic pain. PMID- 27413478 TI - Epiduroscopy as a Diagnostic Tool for the Lower Back Pain and/or Leg Pain. PMID- 27413479 TI - Tapentadol: Can It Kill Two Birds with One Stone without Breaking Windows? AB - Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the u-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence. PMID- 27413480 TI - Presentation of Neurolytic Effect of 10% Lidocaine after Perineural Ultrasound Guided Injection of a Canine Sciatic Nerve: A Pilot Study. AB - BACKGROUND: Phenol and alcohol have been used to ablate nerves to treat pain but are not specific for nerves and can damage surrounding soft tissue. Lidocaine at concentrations > 8% injected intrathecal in the animal model has been shown to be neurotoxic. Tests the hypothesis that 10% lidocaine is neurolytic after a peri neural blockade in an ex vivo experiment on the canine sciatic nerve. METHODS: Under ultrasound, one canine sciatic nerve was injected peri-neurally with 10 cc saline and another with 10 cc of 10% lidocaine. After 20 minutes, the sciatic nerve was dissected with gross inspection. A 3 cm segment was excised and preserved in 10% buffered formalin fixative solution. Both samples underwent progressive dehydration and infusion of paraffin after which they were placed on paraffin blocks. The sections were cut at 4 um and stained with hemoxylin and eosin. Microscopic review was performed by a pathologist from Henry Ford Hospital who was blinded to which experimental group each sample was in. RESULTS: The lidocaine injected nerve demonstrated loss of gross architecture on visual inspection while the saline injected nerve did not. No gross changes were seen in the surrounding soft tissue seen in either group. The lidocaine injected sample showed basophilic degeneration with marked cytoplasmic vacuolation in the nerve fibers with separation of individual fibers and endoneurial edema. The saline injected sample showed normal neural tissue. CONCLUSIONS: Ten percent lidocaine causes rapid neurolytic changes with ultrasound guided peri-neural injection. The study was limited by only a single nerve being tested with acute exposure. PMID- 27413481 TI - The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain. AB - BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level. PMID- 27413482 TI - Serum Vitamin D Status in Iranian Fibromyalgia Patients: according to the Symptom Severity and Illness Invalidation. AB - BACKGROUND: This study was designed to assess serum vitamin D status (25-OHD) in the fibromyalgia (FM) patients and to compare it with a healthy control group. It also aimed to investigate the correlation of serum vitamin D level with FM symptom severity and invalidation experiences. METHODS: A total of 74 consecutive patients with FM and 68 healthy control participants were enrolled. The eligible FM patients completed the Illness Invalidation Inventory (3(*)I), the Revised Fibromyalgia Impact Questionnaire (FIQR) and a short-form health survey (SF-12). Venous blood samples were drawn from all participants to evaluate serum 25-OHD levels. Mann-Whitney tests and multiple logistic regression analyses were performed and Spearman's correlations were calculated. RESULTS: 88.4% of FM patients had low levels of serum 25-OHD. FM patients had significantly higher level of serum 25-OHD than the control group (17.24 +/- 13.50 and 9.91 +/- 6.47 respectively, P = 0.0001). There were no significant correlations between serum 25-OHD levels and the clinical measures of disease impact, invalidation dimensions, and health status. Multiple logistic regression analyses revealed that an increased discounting of the disease by the patient's spouse was associated with a 4-fold increased risk for vitamin D deficiency (OR = 4.36; 95% CI, 0.95-19.87, P = 0.05). CONCLUSIONS: This study showed that although high rates of vitamin D insufficiency or deficiency were seen among FM patients and healthy non-FM participants, but it seems there was no intrinsic association between FM and vitamin D deficiency. Addressing of invalidation experience especially by the patient's spouse is important in management of FM. PMID- 27413483 TI - Risk of Encountering Dorsal Scapular and Long Thoracic Nerves during Ultrasound guided Interscalene Brachial Plexus Block with Nerve Stimulator. AB - BACKGROUND: Recently, ultrasound has been commonly used. Ultrasound-guided interscalene brachial plexus block (IBPB) by posterior approach is more commonly used because anterior approach has been reported to have the risk of phrenic nerve injury. However, posterior approach also has the risk of causing nerve injury because there are risks of encountering dorsal scapular nerve (DSN) and long thoracic nerve (LTN). Therefore, the aim of this study was to evaluate the risk of encountering DSN and LTN during ultrasound-guided IBPB by posterior approach. METHODS: A total of 70 patients who were scheduled for shoulder surgery were enrolled in this study. After deciding insertion site with ultrasound, awake ultrasound-guided IBPB with nerve stimulator by posterior approach was performed. Incidence of muscle twitches (rhomboids, levator scapulae, and serratus anterior muscles) and current intensity immediately before muscle twitches disappeared were recorded. RESULTS: Of the total 70 cases, DSN was encountered in 44 cases (62.8%) and LTN was encountered in 15 cases (21.4%). Both nerves were encountered in 10 cases (14.3%). Neither was encountered in 21 cases (30.4%). The average current measured immediately before the disappearance of muscle twitches was 0.44 mA and 0.50 mA at DSN and LTN, respectively. CONCLUSIONS: Physicians should be cautious on the risk of injury related to the anatomical structures of nerves, including DSN and LTN, during ultrasound-guided IBPB by posterior approach. Nerve stimulator could be another option for a safer intervention. Moreover, if there is a motor response, it is recommended to select another way to secure better safety. PMID- 27413485 TI - Serratus Anterior Plane (SAP) Block Used for Thoracotomy Analgesia: A Case Report. AB - Thoracotomy is a surgical technique used to reach the thoracic cavity. Management of pain due to thoracotomy is important in order to protect the operative respiratory reserves and decrease complications. For thoracotomy pain, blocks (such as thoracic epidural, paravertebral, etc.) and pleural catheterization and intravenous drugs (such as nonsteroidal anti-inflammatory drugs [NSAIDs], and opioids, etc., can be used. We performed a serratus anterior plane (SAP) block followed by catheterization for thoracotomy pain. We used 20 ml 0.25% bupivacaine for analgesia in a patient who underwent wedge resection for a lung malignancy. We provided analgesia for a period of close to seven hours for the patient, whose postoperative VAS (visual analog scale) scores were recorded. We believe that an SAP block is effective and efficient for the management of pain after thoracotomy. PMID- 27413484 TI - Nineth Rib Syndrome after 10(th) Rib Resection. AB - The 12(th) rib syndrome is a disease that causes pain between the upper abdomen and the lower chest. It is assumed that the impinging on the nerves between the ribs causes pain in the lower chest, upper abdomen, and flank. A 74-year-old female patient visited a pain clinic complaining of pain in her back, and left chest wall at a 7 on the 0-10 Numeric Rating scale (NRS). She had a lateral fixation at T12-L2, 6 years earlier. After the operation, she had multiple osteoporotic compression fractures. When the spine was bent, the patient complained about a sharp pain in the left mid-axillary line and radiating pain toward the abdomen. On physical examination, the 10(th) rib was not felt, and an image of the rib-cage confirmed that the left 10(th) rib was severed. When applying pressure from the legs to the 9(th) rib of the patient, pain was reproduced. Therefore, the patient was diagnosed with 9(th) rib syndrome, and ultrasound-guided 9(th) and 10(th) intercostal nerve blocks were performed around the tips of the severed 10(th) rib. In addition, local anesthetics with triamcinolone were administered into the muscles beneath the 9(th) rib at the point of the greatest tenderness. The patient's pain was reduced to NRS 2 point. In this case, it is suspected that the patient had a partial resection of the left 10(th) rib in the past, and subsequent compression fractures at T8 and T9 led to the deformation of the rib cage, causing the tip of the remaining 10(th) rib to impinge on the 9(th) intercostal nerves, causing pain. PMID- 27413486 TI - Continuous Ilioinguinal-iliohypogastric Nerve Block for Groin Pain in a Breast feeding Patient after Cesarean Delivery. AB - Ilioinguinal and iliohypogastric (II/IH) nerve injury is one of the most common nerve injuries following pelvic surgery, especially with the Pfannenstiel incision. We present a case of intractable groin pain, successfully treated with a continuous II/IH nerve block. A 33-year-old woman, following emergency cesarean section due to cephalopelvic disproportion, presented numbness in left inguinal area and severe pain on the labia on the second postoperative day. The pain was burning, lancinating, and exacerbated by standing or movement. However, she didn't want to take additional medicine because of breast-feeding. A diagnostic II/IH nerve block produced a substantial decrease in pain. She underwent a continuous II/IH nerve block with a complete resolution of pain within 3 days. A continuous II/IH nerve block might be a goodoption for II/IH neuropathy with intractable groin pain in breast-feeding mothers without adverse drug reactions in their infants. PMID- 27413487 TI - Clinical Effectiveness of Ultrasound-guided Costotransverse Joint Injection in Thoracic Back Pain Patients. AB - Because of its anatomical location and function, the costotransverse (CTRV) joint can be a source of thoracic back pain. In this retrospective observational study, we evaluated the clinical effectiveness of the CTRV joint injection in thoracic back pain patients with suspected CTRV joint problems. We enrolled 20 thoracic back pain patients with localized tenderness that was provoked by the application of pressure on the affected CTRV joints. We injected it with 0.5 ml of a ropivacaine and triamcinolone mixture at each level. The mean pre-injection pain score decreased by 37.9% (7.2 +/- 1.5 to 4.5 +/- 1.7, P < 0.001) two weeks after CTRV joint injection. In addition, 70% of patients reported an excellent or good level of satisfaction. We demonstrated that an ultrasound-guided injection of the CTRV joint reduced patients' pain scores and led to a high level of satisfaction at short-term follow-ups in patients with suspected CTRV joint problems. PMID- 27413488 TI - Inverse Electrode Placement May Help to Improve Electrotherapeutic Effects in the Field of Chronic Pain Management. PMID- 27413489 TI - Quality of Life and Strabismus Surgery in Children. PMID- 27413490 TI - Corneal Biomechanical Changes Following Toric Soft Contact Lens Wear. AB - PURPOSE: To determine the effect of using toric soft contact lenses on corneal biomechanical properties. METHODS: We enrolled 33 healthy patients with mean age of 23.18 +/- 4.06 and minimal cylinder power of 1 D (-1.98 +/- 0.808 SD) and negative history of contact lens use; keratoconic patients were excluded from the study. Toric soft contact lenses (BIOFINITY, Comfilcon A, Coopervision, Southampton, UK) were fitted in all participants. The Ocular Response Analyzer (Reichert Ophthalmic Instruments, Depew, New York, USA) was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), and the Pentacam HR (Oculus, Inc., Lynnwood, WA, USA) was used to measure central corneal thickness (CCT) and mean keratometry (K mean) before and one week, one month, and three months after using the toric soft contact lenses. RESULTS: CH and CRF were decreased significantly one month after using the contact lens; mean CH decreased from 9.99 +/- 1.44 to 9.59 +/- 1.54 mmHg, and mean CRF decreased from 9.96 +/- 1.71 to 9.63 +/- 1.73 mmHg (P = 0.013 and P = 0.017, respectively). Mean CCT and K mean did not show a significant change during the period of toric soft contact lens use. CONCLUSION: CH and CRF decreased significantly one month after fitting toric soft contact lenses while CCT and Kmean did not change significantly. Corneal biomechanical parameters may alter with toric soft contact lens use and such changes may have implications with long-term use such lenses. PMID- 27413491 TI - Efficacy of Wavefront-guided Photorefractive Keratectomy with Iris Registration for Management of Moderate to High Astigmatism by Advanced Personalized Treatment Nomogram. AB - PURPOSE: To evaluate the efficacy of photorefractive keratectomy (PRK) using the advanced personalized treatment (APT) nomogram for correction of moderate to high astigmatism. METHODS: This prospective interventional case series included 60 consecutive eyes of 30 patients undergoing wavefront-guided PRK (Zyoptix 217 Z100 excimer laser, Bausch & Lomb, Munich, Germany) using the APT nomogram and iris registration for myopic astigmatism. Mitomycin-C was applied intraoperatively in all eyes. Ophthalmic examination was performed preoperatively and 1, 3 and 6 months postoperatively. RESULTS: Preoperatively, mean sphere was -1.68 +/- 2.08 diopters (D), mean refractive astigmatism was -3.04 +/- 1.05 D and mean spherical equivalent (SE) was -3.12 +/- 1.77 D. Six months postoperatively, mean sphere was + 0.60 +/- 0.64 D (P < 0.005), mean cylinder was -0.43 +/- 0.46 D (P < 0.005) and mean SE was + 0.28 +/- 0.48 D (P < 0.005). Hyperopic overcorrection (>= +1.0 D) occurred in 3 (5%) eyes. Postoperatively, root mean square (RMS) of higher order aberrations (HOAs) was significantly increased (P = 0.041). RMS of spherical aberration (Z [4, 0]) showed no significant change after surgery (P = 0.972). CONCLUSION: Considering the acceptable residual refractive error, low rate of hyperopic overcorrection, acceptable uncorrected visual acuity, and low risk of postoperative corneal haze, PRK using the APT nomogram with iris registration and mitomycin-C use is a safe and effective modality for treatment of moderate to high astigmatism. PMID- 27413492 TI - Effect of Photorefractive Keratectomy on Optic Nerve Head Topography and Retinal Nerve Fiber Layer Thickness Measured by Heidelberg Retina Tomograph 3. AB - PURPOSE: To determine whether photorefractive keratectomy (PRK) has a significant effect on optic nerve head (ONH) parameters and peripapillary retinal nerve fiber layer (RNFL) thickness measured by the Heidelberg Retina Tomograph 3 (Heidelberg Engineering GmbH, Heidelberg, Germany) in eyes with low to moderate myopia. METHODS: This prospective, interventional case series, includes 43 consecutive myopic eyes which were assessed on the day of PRK and 3 months postoperatively using the HRT3. Among the stereometric parameters, we compared disc area, linear cup disc ratio, cup shape measure, global rim area, global rim volume, RNFL height variation contour and mean RNFL thickness; out of the Glaucoma Probability Score (GPS) we assessed changes in global value, rim steepness temporal/superior, and temporal/inferior, as well as cup size and cup depth before and after PRK. RESULTS: Mean refractive error before and after PRK were -3.24 +/- 1.31 and -0.20 +/- 0.42 diopters, respectively. No significant change occurred in disc area, linear cup disc ratio, cup shape measure, rim area and rim volume among the stereometric parameters; and in rim steepness temporal/superior and rim steepness temporal/inferior in the GPS before and after PRK using the default average keratometry. However, RNFL height variation contour, mean RNFL thickness, and cup size and depth were significantly altered after PRK (P < 0.05). CONCLUSION: PRK can affect some HRT3 parameters. Although the most important stereometric parameters for differentiating normal, suspect or glaucomatous patients such as rim and cup measurements in stereometric parameters were not changed. PMID- 27413494 TI - Correlations Between Histopathologic Changes and Clinical Features in Pterygia. AB - PURPOSE: To investigate the correlations between clinical findings and histopathologic changes in eyes with pterygium. METHODS: This prospective study included 70 eyes with primary pterygia undergoing surgical excision. Prior to surgery, clinical features of the pterygia including extension over the cornea, redness, fleshiness (based on obscuration of the underlying episcleral vessels), and obliteration of the plica semilunaris were determined. Postoperatively, pterygium specimens were examined by hematoxylin-eosin and trichrome staining to evaluate histopathologic characteristics including vascular density, leukocytic infiltration, stromal elastosis, stromal fibrosis and subepithelial fibrosis. Correlations between clinical findings and histopathologic changes were then investigated. RESULTS: There was a marginally significant correlation between the redness and the fleshiness of pterygium (P = 0.06). Both redness and fleshiness of the pterygium had significant positive correlation with dimensions of the lesion over the cornea. Moreover, larger pterygia were associated with obliteration of the plica semilunaris. Pterygium redness showed a significant correlation with vascular density (P = 0.04), and pterygium fleshiness had a significant correlation with stromal fibrosis (P = 0.04). Pterygium dimensions over the cornea demonstrated a positive correlation with vascular density and a negative correlation with stromal elastosis. CONCLUSION: Redness and fleshiness of pterygium were only marginally correlated with each other, and each one showed a correlation with different histopathologic features. Larger pterygia were associated with more significant changes at the clinical and histopathologic levels. PMID- 27413493 TI - Trends in Indications and Techniques of Corneal Transplantation in Iran from 2006 to 2013; an 8-year Review. AB - PURPOSE: To report changing trends in indications and techniques of corneal transplantation in Iran. METHODS: We reviewed eye bank records of 47,129 patients who had undergone corneal transplantation between 2006 and 2013 at different eye centers throughout Iran. RESULTS: The most common indication for corneal transplantation was keratoconus (KCN, n = 21,350 eyes, 45.3%), followed by bullous keratopathy (BK, n = 8,566 eyes, 18.2%), corneal opacity and scar (COS, n = 7,158 eyes, 15.2%), graft failure (n = 3,252 eyes, 6.9%), corneal dystrophies (n = 2,553 eyes, 5.4%), and infectious keratitis (n = 2,238 eyes, 4.7%). Over the study period, there was a significant increase in the frequency of BK (P = 0.001) and graft failure (P = 0.025), and a significant decrease in the relative frequency of COS (P = 0.012). The prevalence of KCN (P = 0.172), infectious keratitis (P = 0.107), and corneal dystrophies (P = 0.836) remained unchanged. The most common technique of corneal transplantation was penetrating keratoplasty (PKP, n = 33,476 eyes, 71.0%), followed by deep anterior lamellar keratoplasty (DALK, n = 8,363 eyes, 17.7%), Descemet's stripping automated endothelial keratoplasty (DSAEK, n = 3,516 eyes, 7.5%), tectonic (n = 1752, 3.7%), and keratolimbal allograft (KLAL, n = 19 eyes, 0.1%). Regarding the shift in surgical techniques, a significant increase was observed in DSAEK (P < 0.001), whereas PKP was significantly decreased (P = 0.005) over the 8-year period. No significant change was seen in the rates of DALK (P = 0.354), tectonic graft (P > 0.999) and KLAL (P = 0.151). CONCLUSION: KCN was the most common indication and PKP was the most prevalent technique used for corneal transplantation. Significant changes in surgical techniques were observed over the past 8 years; DSAEK demonstrated an increasing trend while PKP showed a decrease. PMID- 27413495 TI - Is the Capsular Bag Perimeter Round or Elliptical? AB - PURPOSE: To report findings that could suggest an elliptical shape of the capsular bag. METHODS: Five eyes of three patients with axial length greater than 24 mm underwent phacoemulsification cataract surgery with plate-haptic multifocal toric intraocular lens (IOL) implantation oriented in the vertical meridian. RESULTS: In all cases, correct orientation of the IOLs was verified 30 minutes after surgery. After 24 hours, all eyes demonstrated unwanted rotation of the IOLs ranging from 15 to 45 degrees. The IOLs remained stable in the new position in all cases until adhesion of the capsular bag took place. CONCLUSION: These observations could suggest that the perimeter of the capsular bag has an elliptical shape. Therefore, the IOL tends to become fixated in a meridian of the capsular bag that best fits the diagonal diameter of the IOL. PMID- 27413496 TI - Three Methods for Correction of Astigmatism during Phacoemulsification. AB - PURPOSE: To compare the safety and efficacy of three methods for correcting pre existing astigmatism during phacoemulsification. METHODS: This prospective, comparative, non-randomized study was conducted from March 2010 to January 2011, and included patients with keratometric astigmatism >=1.25 D undergoing cataract surgery. Astigmatism was corrected using the following approaches: limbal relaxing incisions (LRI) on the steep meridian, extension and suturing of the phaco incision created at the steep meridian (extended-on-axis incision, EOAI), and toric intraocular lens (tIOL) implantation. Keratometric and refractive astigmatism were evaluated 1, 8, and 24 weeks postoperatively. RESULTS: Eighty three eyes of 72 patients (35 male and 37 female) with mean age of 62.4 +/- 14.3 (range, 41-86) years were enrolled. The astigmatism was corrected by using the LRI, EOAI and tIOL implantation methods in 17, 33 and 33 eyes, respectively. Postoperative uncorrected distance visual acuity (UDVA) was significantly improved in all three groups. The difference in postoperative UDVA was not statistically significant among the study groups throughout follow-up except at week 24, when UCVA was significantly better in the tIOL group as compared to the EOAI group (P = 0.024). There is no statistically significant difference of correction index and index of success between three groups at week 24 (P = 0.085 and P = 0.085 respectively). CONCLUSION: There was no significant difference in astigmatism reduction among the three methods of astigmatism correction during phacoemulsification. Each of these methods can be used at the discretion of the surgeon. PMID- 27413497 TI - Outcomes of Descemetopexy with Isoexpansile Perfluoropropane after Cataract Surgery. AB - PURPOSE: To report the indications, anatomical outcomes, functional outcomes and limitations of descemetopexy with intracameral injection of isoexpansile perfluoropropane (14% C3F8) in eyes with Descemet's membrane (DM) detachment after cataract surgery. METHODS: This retrospective non-comparative interventional case series included 67 eyes of 67 patients who underwent descemetopexy at a tertiary eye hospital. The procedure consisted of descemet's membrane reattachment by injecting isoexpansile perfluoropropane (14% C3F8)intracamerally. Outcome measures were reattachment of DM, improvement in visual acuity, resolution of corneal edema, causes for failure of DM reattachment and complications. RESULTS: Sixty-seven eyes of 74 patients were analyzed. Phacoemulsification (56.71%) had the highest DM detachment as compared to manual SICS in 19 (28.36%) and ECCE in 10 (14.93%) eyes. Descemetopexy with 14% C3F8 resulted in anatomical reattachment of DM in 71.64% and functional improvement in visual acuity in 74.63% of treated eyes. The location and the extent of DM detachment did not influence DM reattachment. Complete reattachment of DM occurred in all 26 eyes (100%) with planar type detachments, whereas with non planar type detachments only 22 eyes (53.7%) achieved complete reattachment. CONCLUSION: Descemetopexy with isoexpansile perfluoropropane offers good surgical outcomes regarding visual acuity and resolution of corneal edema. PMID- 27413498 TI - Neuroprotective Effects of Memantine in the Retina of Glaucomatous Rats: An Electron Microscopic Study. AB - PURPOSE: In this experimental study, the effects of systemic memantine administration on the retinal ultrastructure of experimentally induced glaucomatous rats were investigated. METHODS: Twenty-four Wistar albino rats were included in this study. Glaucoma was induced by injecting sodium hyaluronate into the anterior chamber of the rats for a period of three weeks. As a control, 8 rats were sham treated (Group C). Glaucoma induced animals were divided into two groups; Group M (n = 8) received a single daily dose of 10 mg/kg memantine, and Group G received the same volume of saline (n = 8), via intraperitoneal route for a period of six weeks, starting with the induction of glaucoma. Then, all rats were sacrificed and the retinas were prepared for electron microscopic examination. Electron microscopic damage findings were graded between 0 and 4 and mean damage scores for each cell or layer was calculated for each group. Statistical comparison was made between group G and group M. RESULTS: Including the photoreceptor cells, marked ultrastructural changes were observed in the retinas of the animals in group G. The ultrastructural changes in group M were modest and there was no significant cell death. Statistical findings indicated these results. CONCLUSION: Results of the present study suggest that memantine treatment, when started in the early phase of glaucomatous process, may help to preserve the retinal ultrastructure and thus prevent neuronal injury in experimentally induced glaucoma. PMID- 27413500 TI - The Impact of Congenital Strabismus Surgery on Quality of Life in Children. AB - PURPOSE: To assess quality of life (QOL) in children undergoing strabismus surgery. METHODS: This prospective cohort study included 87 children (including 41 boys, 47.1%) with mean age of 8.7 +/- 4.1 years at three academic eye hospitals in Tehran. A modified version of the RAND Health Insurance Study QOL questionnaire was filled based on interviews with parents before and three months after surgery. The questionnaire consisted of 36 Likert scale items ranging in score from 0 to 100, with higher scores representing better function. Relevant items were averaged together and categorized into 11 distinct QOL dimensions. RESULTS: The majority of QOL dimensions improved after strabismus surgery including functional limitation (92.36 +/- 16.78 vs. 82.15 +/- 20.92, P < 0.01), anxiety (68.61 +/- 18.15 vs. 60.28 +/- 19.19, P < 0.01), depression (82.31 +/- 16.42 vs. 72.36 +/- 17.72, P < 0.01), positive well-being (73.33 +/- 14.69 vs. 70.56 +/- 15.96, 0.048), social relations (79.43 +/- 11.52 vs. 68.69 +/- 30.98, 0.002), general health perception (76.4 +/- 16.48 vs. 67.36 +/- 18.9, P < 0.01), resistance/susceptibility (79.72 +/- 13.4 vs. 71.02 +/- 14.58, P < 0.01), satisfaction with development (73.81 +/- 16.07 vs. 70.07 +/- 14.98, P = 0.006), and eye alignment concerns (75.44 +/- 15.89 vs. 53.14 +/- 26.61, P < 0.01). Only self-reported prior health (71.73 +/- 15.9 vs. 72.78 +/- 15.29, P = 0.33) and parent-child closeness (72.92 +/- 15.82 vs. 72.5 +/- 17.99, P = 0.73) did not significantly improve. The amount of ocular realignment (more vs. less than 20 prism diopters [PD]) had a direct correlation with improvement in subscales of satisfaction with development (0.019) and eye alignment concerns (0.028). CONCLUSION: Strabismus surgery positively impacts physical and psychosocial function in children. Children with a greater amount of correction experienced more QOL improvement after surgery. PMID- 27413499 TI - Short-term Efficacy of Intravitreal Dexamethasone Implant in Vitrectomized Eyes with Recalcitrant Diabetic Macular Edema and Prior Anti-VEGF Therapy. AB - PURPOSE: To determine the efficacy of an intravitreal dexamethasone implant (IDI) for diabetic macular edema (DME) in vitrectomized eyes. METHODS: This interventional retrospective consecutive case series included vitrectomized eyes undergoing IDI placement for treatment of recalcitrant DME between June 2011 and June 2014. All patients had previously received anti-VEGF therapy (ranibizumab or bevacizumab). Primary endpoints were changes in visual acuity (VA) and central retinal thickness (CRT) from baseline values one month after device implantation. Secondary endpoints were VA and CRT changes at 3 months. RESULTS: A total of 8 eyes of 8 patients met the inclusion criteria. One month after IDI placement, there was a significant (p = 0.01) improvement in VA from 0.79 +/- 0.52 logMAR (20/123 Snellen equivalent) to 0.64 +/- 0.55 logMAR (20/88), meanwhile CRT improved from 455.75 +/- 123.19 to 295.00 +/- 90.39 MUm (p = 0.02). These findings persisted at 3 months. CONCLUSION: In vitrectomized eyes previously treated with anti-VEGF agents for recalcitrant DME, implantation of the IDI appears to be efficacious in improving VA and CRT at 1-month with the observed benefits persisting for at least for 3 months. PMID- 27413501 TI - Fornix Reconstruction with Amniotic Membrane Transplantation: A Cosmetic Remedy for Blind Patients. AB - PURPOSE: Fornix contracture is an obstacle for fitting a prosthesis in blind or enucleated patients, and may lead to disfigurement and psychological issues. This study evaluates the efficacy of amniotic membrane transplantation (AMT) for fornix reconstruction with the aim of better retention of the ocular prosthesis. METHODS: This non-comparative interventional case series includes eighteen blind eyes with fornix deformity in which a cosmetic prosthesis could not be retained. Various causative factors included symblepharon, cyst formation and fornix shortening after enucleation. AMT was performed along with correction of symblepharon, cicatrix release, and excision of the cyst with or without anchoring sutures to reform the fornix. RESULTS: Mean fornix depth pre- and post operation were 3.72 +/- 0.69 and 7.13 +/- 0.81 mm, respectively. Fornix deepening was achieved successfully in 15 cases (83.33%). Partial success was achieved in 1 case (5.66%); the remaining two cases (11.11%) were considered as failure despite repeat surgery. Both of these patients suffered from extensive symblepharon formation. Satisfactory results, i.e. formation of a deep fornix to hold the ocular prosthesis, could be achieved in 16 (89.99%) cases. There were no serious complications such as infection or graft rejection. CONCLUSION: AMT can be a viable option for fornix reconstruction. It has a high success rate in subjects with blind eyes and moderate fornix shortening who are unable to retain an ocular prosthesis. PMID- 27413502 TI - Vision Screening of Younger School Children by School Teachers: A Pilot Study in Udaipur City, Western India. AB - PURPOSE: To assess the reliability of school teachers for vision screening of younger school children and to study the pattern of vision problems. METHODS: In this cross-sectional study, trained school teachers screened 5,938 school children aged 3 to 8 years for vision and ocular disorders. Children were cross screened by professionals to assess the reliability of the teachers in vision screening and detecting ocular disorders in these children. The pattern of visual acuity, ametropia and ocular disorders was studied. RESULTS: Sensitivity and specificity of the vision screening by school teachers was 69.2% (95% CI: 66.8 71.5%) and 95.3% (95% CI: 94.5-95.8%), respectively. The positive predictive value was 83.5% (95% CI: 81.4-85.6%) and negative predictive value was 89.8% (95% CI: 88.8-90.6%). The kappa statistic was 0.68 (95% CI: 0.66-0.7). CONCLUSION: School teachers could effectively screen younger school children for vision assessment and ocular disorders. PMID- 27413503 TI - Update on Normal Tension Glaucoma. AB - Normal tension glaucoma (NTG) is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP) constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases), systemic calcium channel blockers (such as nifedipine) and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG. PMID- 27413505 TI - Favorable Long-term Prognosis of Cataract Surgery in Herpes Zoster Ophthalmicus. AB - PURPOSE: Scleritis is a rare presentation of herpes zoster ophthalmicus, complicated most commonly by iridocyclitis and raised intraocular pressure. These complications can recur in subsequent years, therefore they should be managed well. CASE REPORT: We describe a female patient who developed scleritis, complicated cataract and secondary glaucoma 2 years after being diagnosed by HZO. Secondary glaucoma was managed medically, and the patient underwent extracapsular cataract extraction for the complicated cataract. Final visual acuity was 6/6 and IOP was 22.4 mm Hg. This is a rare report describing favorable long-term (>20 years) prognosis for surgical management of cataract associated with HZO together with scleritis, secondary glaucoma and post-herpetic neuralgia. CONCLUSION: A favorable outcome may be attained with surgery for complicated cataract associated with HZO if the condition is managed optimally and intraocular inflammation is well controlled. PMID- 27413506 TI - Hydrophilic Acrylic Intraocular Lens Opacification after Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To report hydrophilic acylic intraocular lens (IOL) opacification after Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) in an eye with multiple prior intraocular surgeries and iatrogenic aniridia. CASE REPORT: A 34 year-old woman with history of penetrating keratoplasty (PKP) for advanced keratoconus and subsequent Urrets-Zavalia Syndrome (UZS) underwent phacoemulsification and hydrophilic acrylic IOL implantation for her cataract. In order to control post-PKP glaucoma, multiple glaucoma surgeries including two glaucoma drainage implants were performed. As the original corneal graft failed, the patient subsequently underwent re-PKP. Four years later, she underwent DSAEK for treatment of the second graft failure. Ten months after DSAEK, a double semi circular pattern of IOL opacification was observed on the anterior surface of the IOL. The patient did not report any complaints and we decided not to exchange the IOL. CONCLUSION: In an eye with UZS and iatrogenic aniridia, IOL opacification may result from direct contact between the IOL surface and exogenous air. Aniridia can be a risk factor for development of IOL opacification after DSAEK. Further studies are required to confirm this hypothesis. PMID- 27413507 TI - Bilateral Presumed Tuberculous Choroiditis. AB - PURPOSE: To describe a case of bilateral presumed tuberculous choroiditis which resolved promptly with a short course of antituberculous therapy. CASE REPORT: A 44-year-old lady presented with bilateral visual loss of 8 months'duration. Considering the presence of pan-uveitis, severe macular edema, multifocal leakage on fluorescein angiography, positive tuberculin skin test, and after excluding other diseases, she underwent anti-tuberculous therapy (ATT) for disseminated choroiditis due to presumed ocular tuberculosis. She improved promptly and completely. There were no signs of relapse 18 months after completion of the treatment course. In a young patient with disseminated choroiditis and relatively short duration of symptoms, a course of ATT for 6 months may effectively treat the disease preventing relapse for a considerable period of time. CONCLUSION: In Presumed Tuberculous chroiditis early diagnosis is crucial for prompt and complete improvement. PMID- 27413504 TI - Neuroprotection in Glaucoma. AB - Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC) loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP) reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies. A few agents (such as brimonidine or memantine) with neuroprotective effects in experimental studies have advanced to clinical trials; however the results of clinical trials for these agents have not been conclusive. Nevertheless, lack of compelling clinical evidence has not prevented the off label use of some of these compounds in glaucoma practice. Stem cell transplantation has been reported to halt experimental neurodegenerative disease processes in the absence of cell replacement. It has been hypothesized that transplantation of some types of stem cells activates multiple neuroprotective pathways via secretion of various factors. The advantage of this approach is a prolonged and targeted effect. Important concerns in this field include the secretion of unwanted harmful mediators, graft survival issues and tumorigenesis. Neuroprotection in glaucoma, pharmacologically or by stem cell transplantation, is an interesting subject waiting for broad and multidisciplinary collaborative studies to better clarify its role in clinical practice. PMID- 27413508 TI - Massive Retinal Pigment Epithelial Detachment Following Acute Hypokalemic Quadriparesis in Dengue Fever. AB - PURPOSE: To describe an unusual retinal manifestation of dengue fever in an endemic region. CASE REPORT: A 35 year old male presenting with acute onset decreased vision in his right eye, was found to have a massive retinal pigment epithelial detachment (PED) extending up to the vascular arcades. He had been diagnosed with acute hypokalemic quadriparesis in dengue fever in the preceding week, which had resolved following treatment. The patient was managed conservatively. At three months follow up, there was spontaneous flattening of the PEDs with improvement in visual acuity. CONCLUSION: Dengue fever complicated by acute hypokalemic quadriparesis can be associated with PED, which can be large. The condition resolves spontaneously and bears a good prognosis. PMID- 27413509 TI - 16-year-old Girl with Diplopia and Unilateral Upper Lid Ptosis. PMID- 27413510 TI - Ultra-wide Field Fluorescein Angiography in Retinitis Pigmentosa with Intermediate Uveitis. PMID- 27413511 TI - Wound Modulation with Botulinum Toxin. PMID- 27413512 TI - Posterior Scleral Thinning Accompanies Increased Vitreous Chamber Depth in Myopia. PMID- 27413513 TI - Estimating the Esophagus Cancer Incidence Rate in Ardabil, Iran: A Capture Recapture Method. AB - BACKGROUND: Accurate cancer registry and awareness of cancer incidence rate is essential in order to define strategies for cancer prevention and control programs. Capture-recapture methods have been recommended for reducing bias and increase the accuracy of cancer incidence estimation. OBJECTIVES: This study aimed to estimate the esophagus cancer incidence by capture-recapture method based on Ardabil population-based cancer registry data. PATIENTS AND METHODS: Total new cases of esophagus cancer reported by three sources of pathology reports, medical records, and death certificates to Ardabil province cancer registry center in 2006 and 2008 were enrolled in the study. All duplicated cases between three sources were identified and removed using Excel software. Some characteristics such as name, surname, father's name, date of birth and ICD codes related to their cancer type were used for data linkage and finding the common cases among three sources. The incidence rate per 100,000 was estimated based on capture-recapture method using the log-linear models. We used BIC, G(2) and AIC statistics to select the best-fit model. RESULTS: After removing duplicates, total 471 new cases of esophagus cancer were reported from three sources. The model with linkage between pathology reports, medical record sources and independence with the death certificates source was the best fitted model. The reported incidence rate for the years 2006 and 2008 was 18.77 and 18.51 per 100,000, respectively. In log-linear analysis, the estimated incidence rate for the years 2006 and 2008 was 49.71 and 53.87 per 100,000 populations, respectively. CONCLUSIONS: Based on the obtained results, it can be concluded that none of the sources of pathology reports, death certificates and medical records individually or collectively were fully covered the incidence cases of esophagus cancer and need to apply some changes in data abstracting and case finding. PMID- 27413515 TI - Sex-related Difference in Protective Role of Aerobic Exercise against Cisplatin induced Hepatotoxicity. PMID- 27413514 TI - How to Find Lessons from the Public Health Literature: Example of a Scoping Study Protocol on the Neighborhood Environment. AB - BACKGROUND: As key determinants of many favorable health and quality of life outcomes, it is important to identify factors associated with mobility and social participation. Although several investigations have been carried out on mobility, social participation and neighborhood environment, there is no clear integration of these results. This paper presents a scoping study protocol that aims to provide a comprehensive understanding of how the physical and social neighborhood environment is associated with or influences mobility and social participation in older adults. METHODS: The rigorous methodological framework for scoping studies is used to synthesize and disseminate current knowledge on the associations or influence of the neighborhood environment on mobility and social participation in aging. Nine databases from public health and other fields are searched with 51 predetermined keywords. Using content analysis, all data are exhaustively analyzed, organized, and synthesized independently by two research assistants. DISCUSSION: A comprehensive synthesis of empirical studies provides decision makers, clinicians and researchers with current knowledge and best practices regarding neighborhood environments with a view to enhancing mobility and social participation. Such a synthesis represents an original contribution and can ultimately support decisions and development of innovative interventions and clear guidelines for the creation of age-supportive environments. Improvements in public health and clinical interventions might be the new innovation needed to foster health and quality of life for aging population. Finally, the aspects of the associations or influence of the neighborhood environment on mobility and social participation not covered by previous research are identified. CONCLUSIONS: Among factors that impact mobility and social participation, the neighborhood environment is important since interventions targeting it may have a greater impact on an individual's mobility and social participation than those targeting individual factors. Although investigations from various domains have been carried out on this topic, no clear integration of these results is available yet. PMID- 27413516 TI - Potential Effects of Pomegranate on Lipid Peroxidation and Pro-inflammatory Changes in Daunorubicin-induced Cardiotoxicity in Rats. AB - BACKGROUND: Daunorubicin-induced acute cardiotoxicity caused by oxidative stress and free radical formation. Pomegranate possessed a significant in vitro free radical scavenging activity. Therefore, the aim of this study was estimations of the role of pomegranate effects in daunorubicin-induced cardiotoxicity. METHODS: A total of 21 Sprague male rats were allocated into three groups, seven animals in each group. Group A: Control group received distilled water. Group B: Treated group with daunorubicin 20 mg/kg via intraperitoneal injection daily for the 12(th) day for total cumulative dose of 240 mg/kg. Group C: Pretreatment group with pomegranate 25 mg/kg for 6 days orally, then daunorubicin 20 mg/kg administrated concomitantly for the next 6 days with a cumulative dose of 120 mg/kg. Cardiac troponin I([cTn I] pg/ml), malondialdehyde (MDA) (ng/ml), interleukin 17 (IL-17 pg/ml), and cardiac lactate dehydrogenase (LDH) (pm/ml), all these biomarkers were used to measure the severity of cardiotoxicity. RESULTS: Daunorubicin at a dose of 20 mg/kg lead to pronounced cardiac damage that reflected on through elevations of serum cTn and serum LDH levels significantly P < 0.01, it induced lipid peroxidation during cardiotoxicity that reflected through an elevation in the serum MDA significantly P < 0.01, moreover, daunorubicin induces pro-inflammatory changes in cardiotoxicity; it raises the IL 17 serum level significantly P < 0.01 as compared with control. Pomegranate pretreatment demonstrated a significant cardioprotection from daunorubicin induced cardiotoxicity; it attenuated the cardiac damage through reduction of cTn, LDH, MDA, and serum IL-17 level significantly P < 0.01 as compared with daunorubicin-treated group. CONCLUSIONS: Pomegranate demonstrated significant cardioprotection in daunorubicin-induced cardiotoxicity through reduction of oxidative stress, lipid peroxidation, pro-inflammatory, and cardiac injury biomarkers. PMID- 27413518 TI - Importance of Micronutrient Supplementation Programme in Childhood to Reduce Child Mortality: The Haryana Experience. PMID- 27413517 TI - Trend of Smear-positive Pulmonary Tuberculosis in Iran during 1995-2012: A Segmented Regression Model. AB - BACKGROUND: Describing trend in tuberculosis (TB) over time can play an important role to assess the disease control strategies and predict the future morbidity and mortality. This study aimed to determine the incidence trend of smear positive pulmonary tuberculosis (SPPT) in sub-age and sex groups during the years of 1995-2012. METHODS: This retrospective cohort study was performed in 2015 by using the dataset regarding National Statistics of SPPT reported by World Health Organization during 1995-2012. Annual percent changes (APCs) and average annual percent changes (AAPCs) were estimated to determine the summery statistics of trend using segmented regression model. RESULTS: During 1995-2012, there were 96,579 SPPT case notifications in Iran (male to female ratio: 0.99). There was only one change point in 1997 for SPPT incidence in subgroups of age and sex during 1995-2012. The AAPCs for both genders and also all three age groups had a significant descending trend during the time period (P < 0.05). CONCLUSIONS: Our results showed a downward trend in the SPPT incidence. It seems that to achieve the set goals and high successful in TB control program especially reduction in SPPT, pay more attention to old age and males should be considered. In addition, improvement of clinical and medical care services and notification processes would be imperative. PMID- 27413519 TI - Comparison of Glibenclamide and Insulin on Neonatal Outcomes in Pregnant Women with Gestational Diabetes. AB - BACKGROUND: Untreated or poorly controlled gestational diabetes can cause serious complications for mother and newborn. Glibenclamide is rarely used in treating mothers with this disease. This study aimed at comparing the effect of glibenclamide and insulin on neonatal outcomes in women with gestational diabetes mellitus. METHODS: In this randomized controlled clinical trial, 249 pregnant women aged 18-45 years within the 11(th)-33(rd) weeks of gestation with gestational diabetes, single fetus pregnancy, and in need of hyperglycemia treatment were entered and grouped randomly as either glibenclamide or insulin. In the insulin group (n = 129), insulin was administered with an initial dose of 0.2 IU/kg subcutaneously twice per day, whereas in the glibenclamide group (n = 120), 1.25 mg oral glibenclamide was administered once daily and increased if needed. RESULTS: The results showed no significant difference in means age, gestational age, and body mass index between women in the two groups. In addition, there were no significant differences in the frequency of neonatal hypoglycemia, anomaly, hyperbilirubinemia, admission in Neonatal Intensive Care Unit (NICU), and neonatal respiratory distress between two groups. Macrosomia was lower in the glibenclamide group than the insulin group (3.3% vs. 13.2%, respectively, P = 0.005). Regression logistics model results showed that the type of treatment (odds ratio [OR]: 4.62; confidence interval [CI]: 1.45-14.02; P = 0.01) and gestational age at delivery (OR: 1.41; CI: 1.04-1.74; P = 0.01) were as predictor factors of macrosomia. CONCLUSIONS: The results of this study revealed that glibenclamide is able to reduce the risk of fetal macrosomia without increasing neonatal anomalies, jaundice, hypocalcemia, infant respiratory distress, and NICU admission. PMID- 27413520 TI - Massive Pulmonary Embolism at the Onset of Acute Promyelocytic Leukemia. AB - Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission. PMID- 27413521 TI - Clinical and Laboratory Characteristics of Dengue-Orientia tsutsugamushi co Infection from a Tertiary Care Center in South India. AB - BACKGROUND: Concurrent infection with multiple pathogens is common in tropics, posing diagnostic and treatment challenges. Although co-infections of dengue, malaria, leptospirosis and typhoid in various combinations have been described, data on dengue and scrub typhus co-infection is distinctly limited. METHODOLOGY: This study was a retrospective analysis of dengue and scrub typhus co-infection diagnosed between January 2010 and July 2014 at a tertiary care center. Clinical and laboratory features of these cases were compared with age and gender-matched patients with isolated dengue fever and isolated scrub typhus. Positive test for dengue non-structural 1 (NS1) antigen was considered diagnostic of dengue whereas scrub typhus was diagnosed by IgM scrub antibodies demonstrated by ELISA. RESULTS: There were 6 cases of dengue-scrub co-infection during the review period which fitted clinical and laboratory profile with a mean age of 42.5 years. Fever, headache, and arthralgia were common. Normal hemoglobin, significant thrombocytopenia, transaminitis, and hypoalbuminemia were identified in these patients. Compared to patients with isolated dengue, those with co-infection had higher pulse rate, lower systolic blood pressure, normal leucocyte counts, higher levels of liver enzymes, greater prolongation of partial thromboplastin time (aPTT) and lower serum albumin. Co-infection was characterized by a lower nadir platelet count compared to scrub typhus, and lesser time to nadir platelet count and longer duration of hospital stay compared to either isolated dengue or scrub typhus. CONCLUSION: Dengue-scrub typhus co-infection may be under-diagnosed in tropics, particularly confounded during dengue epidemics. Normal leukocyte counts, early drop in platelets and hypoalbuminemia in dengue patients could be clues to concurrent scrub typhus infection. Prompt recognition and treatment of scrub typhus in such cases may reduce unnecessary hospital stay and cost. PMID- 27413522 TI - Molecular Heterogeneity of Glucose-6-Phosphate Dehydrogenase Deficiency in Burkina Faso: G-6-PD Betica Selma and Santamaria in People with Symptomatic Malaria in Ouagadougou. AB - The G-6-PD deficiency has an important polymorphism with genotypic variants such as 202A/376G, 376G/542T and 376G/968T known in West African populations. It would confer protection against severe forms of malaria although there are differences between the various associations in different studies. In this study we genotyped six (06) variants of the G-6-PD gene in people with symptomatic malaria in urban areas in Burkina Faso. One hundred and eighty-two (182) patients who tested positive using rapid detection test and microscopy were included in this study. A regular PCR with the GENESPARK G6PD African kit was run followed by electrophoresis, allowing initially to genotype six SNPs (G202A, A376G, A542T, G680T, C563T and T968C). Women carrying the mutations 202A and/or 376G were further typed by real-time PCR using TaqMan probes rs1050828 and rs1050829. In the study population the G-6-PD deficiency prevalence was 9.9%. In addition of G 6-PD A- (202A/376G) variant, 376G/542T and 376G/968T variants were also detected. Hemoglobin electrophoresis revealed that 22.5% (41/182) of the individuals had HbAC compared with2.2% with HbAS and one individual had double heterozygous HbSC. There was no correlation between the G-6-PD deficiency or haemoglobinopathies and symptomatic malaria infections in this study. Our study confirms that the G-6-PD deficiency does not confer protection against Plasmodium falciparum infections. As opposed to previous genotyping studies carried out in Burkina Faso, this study shows for the first time the presence of the variant A- (376G/968C) and warrants further investigation at the national level and in specific ethnic groups. PMID- 27413523 TI - Bendamustine and Rituximab, as First Line Treatment, in Intermediate, High Risk Splenic Marginal Zone Lymphomas of Elderly Patients. AB - BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a chronic B-cell lymphoproliferative disorder, comprising less than 2% of non-Hodgkin's lymphomas, and affecting mainly middle-aged and elderly patients with a median survival of >10 years. The typical clinical features of SMZL include splenomegaly. Treatment should be patient-tailored and can range from a 'watchful waiting' approach for asymptomatic patients without cytopenias to surgery, localized radiation therapy or immuno/chemotherapies. Recently, the combination of rituximab and Bendamustine (R-Benda) has been defined as highly active in patients with follicular lymphomas, but little is known about the efficacy of R-Benda in SMZL. AIM OF THE STUDY: The purpose of this retrospective study was to report our experience on the efficacy of R-Benda as first line treatment in 23 consecutive elderly SMZL patients. RESULTS: All patients had a complete resolution of splenomegaly along with restoration of their blood counts. Nineteen patients (83%) achieved a complete response (CR) to therapy; three patients (13%) achieved a partial response (PR).Ten patients (43%) obtained molecular remission. Toxicities were mild and mainly haematological and result in dose reductions for fourteen patients. CONCLUSIONS: Our data suggest a high activity and good tolerance of R Benda, despite dose reduction due to potential toxicity. PMID- 27413525 TI - Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series. AB - BACKGROUND: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. METHOD: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. RESULTS: Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series. CONCLUSION: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted. PMID- 27413524 TI - CMV in Hematopoietic Stem Cell Transplantation. AB - Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called "the troll of transplantation". One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future. PMID- 27413526 TI - The ICET-A Survey on Current Criteria Used by Clinicians for the Assessment of Central Adrenal Insufficiency in Thalassemia: Analysis of Results and Recommendations. AB - BACKGROUND: In March 2015, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) implemented a two-step survey on central adrenal insufficiency (CAI) assessment in TM patients and after analysis of the collected data, recommendations for the assessment of hypothalamic-pituitary- adrenal (HPA) axis in clinical practice were defined. METHODS: To ascertain the current practice for assessment of CAI in thalassemia, the Coordinator of ICET-A sent two questionnaires by email: i) The first to evaluate the current interpretation of basal serum cortisol level (first step) and ii) The second to assess the current usage of ACTH test and the variability in practice" (second step). Based on the surveys the core ICET-A group prepared the recommendations for the assessment of suspected CAI in thalassemia (third step). RESULTS: A total of 19 thalassemologists/endocrinologists have participated in the first survey and 35 specialists participated in the second step questionnaire. The study demonstrated a considerable variability in almost all aspects of relevant current criteria used for the diagnosis of CAI. An ROC analysis using peak value > 20 MUg/dl (> 550 nmol/L), after ACTH stimulation test, was performed with the aim of identifying the optimal basal serum cortisol cut-off. The optimal threshold that maximizes sensitivity plus specificity for morning basal cortisol against peak post-ACTH value >20 MUg/dl (>550 nmol/L) was 10 MUg/dl (275 nmol/L). Furthermore, the values associated with the highest negative predictive value (NPV) and highest, positive predictive value (PPV) were 4.20 (115 nmol/L) and 18.45 MUg/dl (510 nmol/L), respectively. Surprisingly, 20 specialists in thalassemia working in blood bank, thalassemia centres (day hospital), internal medicine, hematology and onco-hematology had poor knowledge and experience in testing for CAI and stopped filling the questionnaire after the second question. In contrast, 9 endocrinologists (8 pediatricians) and 6 hematologists working in collaboration with endocrinologists completed the questionnaire. CONCLUSIONS: While waiting for more extensive adequately powered and targeted studies, physicians should adopt an acceptable policy for accurate assessment of HPA in TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are also recommended. The ICET-A recommendations are reported in order to facilitate for interested physicians the approach to a successful assessment of adrenal function in thalassemia. PMID- 27413527 TI - Parasitic Infections in Hematopoietic Stem Cell Transplantation. AB - Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID- 27413528 TI - Surveillance and Control of Antibiotic Resistance in the Mediterranean Region. AB - Antibiotic resistance is one of the most relevant problems in the healthcare: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising length to stay (LOS), morbidity and mortality in those patients. The importance of the antibiotic resistance and its spread around the world, gave rise to the activation of several surveillance systems, based especially on the collection of laboratory data to local or national level. The objective of this work is to carry out a review of the scientific literature existing on the topic and scientific activities related to surveillance of antibiotic resistance in the countries bordering the Mediterranean Sea. Recent Data from European Centre for Disease Prevention and Control (November 2015) show, for different combinations bacterium-drug, an increase of resistance from North to South and from West to East of Europe. It is of particular concern the phenomenon of resistance carried out by some gram-negative, specifically Klebsiella pneumoniae and Escherichia coli to third-generation cephalosporin, often combined in opposition to fluoroquinolones and aminoglycosides. Is particularly high the incidence of resistance to carbapenems by strains of Enterobacteriaceae (Klebsiella included). The resistance exerted by MRSA (Methicillin-resistant Staphylococcus aureus) continues to be relevant, albeit showing some decline in recent years. The incidence of resistance carried on by Streptococcus pneumoniae is stable and is mainly relevant to macrolides. Finally, a significant increase in recording relatively exercised by Enterococcus faecium to Vancomycin. Detecting, preventing, and controlling antibiotic resistance requires strategic, coordinated, and sustained efforts. It also depends on the engagement of governments, academia, industry, healthcare providers, the general public, and the agricultural community, as well as international partners. Committing to combating antibiotic-resistant microbes does support patient care, economic growth, agriculture, and economic and national security. PMID- 27413529 TI - Conserved expression of vertebrate microvillar gene homologs in choanocytes of freshwater sponges. AB - BACKGROUND: The microvillus is a versatile organelle that serves important functions in disparate animal cell types. However, from a molecular perspective, the microvillus has been well studied in only a few, predominantly vertebrate, contexts. Little is known about how differences in microvillar structure contribute to differences in function, and how these differences evolved. We sequenced the transcriptome of the freshwater sponge, Ephydatia muelleri, and examined the expression of vertebrate microvillar gene homologs in choanocytes the only microvilli-bearing cell type present in sponges. Sponges offer a distant phylogenetic comparison with vertebrates, and choanocytes are central to discussions about early animal evolution due to their similarity with choanoflagellates, the single-celled sister lineage of modern animals. RESULTS: We found that, from a genomic perspective, sponges have conserved homologs of most vertebrate microvillar genes, most of which are expressed in choanocytes, and many of which exhibit choanocyte-specific or choanocyte-enriched expression. Possible exceptions include the cadherins that form intermicrovillar links in the enterocyte brush border and hair cell stereocilia of vertebrates and cnidarians. No obvious orthologs of these proteins were detected in sponges, but at least four candidate cadherins were identified as choanocyte-enriched and might serve this function. In contrast to the evidence for conserved microvillar structure in sponges and vertebrates, we found that choanoflagellates and ctenophores lack homologs of many fundamental microvillar genes, suggesting that microvillar structure may diverge significantly in these lineages, warranting further study. CONCLUSIONS: The available evidence suggests that microvilli evolved early in the prehistory of modern animals and have been repurposed to serve myriad functions in different cellular contexts. Detailed understanding of the sequence by which different microvilli-bearing cell/tissue types diversified will require further study of microvillar composition and development in disparate cell types and lineages. Of particular interest are the microvilli of choanoflagellates, ctenophores, and sponges, which collectively bracket the earliest events in animal evolution. PMID- 27413530 TI - Significant discrepancies exist between clinician assessment and patient self assessment of functional capacity by validated scoring tools during preoperative evaluation. AB - BACKGROUND: Preoperative assessment of functional capacity is necessary to direct decisions regarding cardiac evaluation and may help identify patients at high risk for perioperative complications. Patient self-triage regarding functional capacity could be useful for discerning which patients benefit from a clinician evaluation at a Preoperative Evaluation Center prior to the day of surgery. We evaluated the feasibility of preoperative, patient self-triage regarding functional capacity. METHODS: Patients were recruited immediately prior to their preoperative evaluation. Study participants completed electronic versions of the Duke Activity Status Index (DASI) and the Patient-Reported Outcomes Measurement System (PROMIS)-Short Form 12a-Physical Function. DASI and PROMIS questionnaire responses were scored and evaluated for correlation with clinician assessments of functional capacity. Correlation was analyzed around the dichotomous outcome of <4 metabolic equivalents of task (METs) or >=4 METs. Patients also evaluated the usability of the questionnaires. RESULTS: After IRB approval, 204 patients were enrolled and completed both DASI and PROMIS questionnaires. Clinicians assessed functional capacity at <4 METs for 109 patients (53.4 %) compared to 18 (8.8 %) patient self-assessments <4 METs as estimated by DASI. These results represent a significant discrepancy between assessments (Fisher's exact, two-tailed P value <0.0001). The standard T-score of PROMIS estimates of functional capacity correlated with DASI estimates (R (2) 0.76). The mean and standard deviation for PROMIS T-scores were 43.3 and 9.86, respectively (mean 50.0; SD 10.0 for the general population). Of the 203 patients who completed the entire study survey, 192 (94.6 %) stated that they did not require assistance from another person, and 187 (94 %) responded either "agree" or "strongly agree" to the DASI questionnaire being "easy to understand" and "easy to complete;" 186 (93 %) and 188 (94 %), respectively, responded similarly to the PROMIS questionnaire. CONCLUSIONS: While both electronic questionnaires were easy to understand and complete for most study participants, there was a significant discrepancy between clinician assessments and patient self-assessments of functional capacity. Further study is needed to determine if either patient self-triage by means of activity questionnaires or clinician evaluation is valid and reliable in the preoperative setting. PMID- 27413531 TI - Evaluating the neonatal BCG vaccination programme in Ireland. AB - BACKGROUND: The aim of this study was to compare the cost effectiveness of the current Irish programme of universal BCG vaccination of infants versus a programme which considered selectively vaccinating high risk infants using decision analytical modelling. METHODS: The efficacy of the BCG vaccine was re evaluated to inform a decision analytical model constructed to follow a birth cohort of vaccinated and unvaccinated infants over a 15 year time horizon. The number of life years gained (LYG) was the primary outcome measure and this was compared to the net cost of the vaccination strategies. RESULTS: In the base case analysis, the incremental cost effectiveness ratios (ICERs) for the universal strategy and selective strategy vs no vaccination were ?204,373/LYG and ?143,233/LYG respectively. When comparing the incremental difference in moving from the universal to the selective strategy, the selective strategy costs ?1,055,692 less per 4.8 life years lost per birth cohort. One way sensitivity analyses highlighted that a move from the universal to the selective strategy was particularly sensitive to the estimate of vaccine efficacy against deaths, the cost of administering the vaccine and the multiplier used to apportion risk of contracting tuberculosis. Probabilistic analysis suggested that a move from a universal based strategy to a selective based strategy could be deemed cost effective (probability of cost effectiveness is 76.8 %). CONCLUSION: The results of the study support the protective effect of the BCG vaccine in infants and quantified the cost effectiveness of the current BCG vaccination strategy and the decremental difference in moving to a selective strategy. This analysis highlights that the additional protection offered by the universal vaccination strategy is small compared to that of the selective strategy. Consideration should therefore be given to the implementation of a selective vaccination strategy, and diverting resources to improve TB case management and control. PMID- 27413533 TI - A paradox in individual-based models of populations. AB - The standard dynamic energy budget model is widely used to describe the physiology of individual animals. It assumes that assimilation rate scales with body surface area, whereas maintenance rate scales with body volume. When the model is used as the building block of a population model, only limited dynamical behaviour, the so-called juvenile-driven cycles, emerges. The reason is that in the model juveniles are competitively superior over adults, because juveniles have a higher surface area-to-volume ratio. Maintenance requirements for adults are therefore relatively large, and a reduced assimilation rate as a result of lowered food levels will easily become insufficient. Here, an alternative dynamic energy budget model is introduced that gives rise to adult-driven cycles, which may be closer to what is often observed in reality. However, this comes at the price of a rather odd description of the individual, in that maintenance scales with body area and assimilation rate with body volume, resulting in unbounded exponential body growth. I make a plea to solve the paradox and come up with reliable descriptions at both the individual and the population level. PMID- 27413532 TI - Endocrine responses to diverse stressors of capture, entanglement and stranding in leatherback turtles (Dermochelys coriacea). AB - Leatherback turtles (Dermochelys coriacea) are exposed to many anthropogenic stressors, yet almost no data on stress physiology exist for this species. As a first step toward understanding the physiological responses of leatherback turtles to stress, and with the particular goal of assessment of the effect of capture, we quantified corticosterone (an adrenal stress hormone) and thyroxine (a regulator of metabolic rate, often inhibited by chronic stress) in 17 healthy leatherback turtles captured at sea for scientific study, with comparisons to 15 'distressed' leatherbacks that were found entangled in fishing gear (n = 8), confined in a weir net (n = 1) or stranded on shore (n = 6). Distressed leatherbacks had significantly elevated corticosterone (mean +/- SEM 10.05 +/- 1.72 ng/ml, median 8.38 ng/ml) and free thyroxine (mean 0.86 +/- 0.37 pg/ml, median 0.08 pg/ml) compared with healthy leatherbacks sampled immediately before release (after ~40 min of handling; corticosterone, mean 4.97 +/- 0.62 ng/ml, median 5.21 ng/ml; and free thyroxine, mean 0.05 +/- 0.05 pg/ml, median 0.00 pg/ml). The elevated thyroxine in distressed turtles compared with healthy turtles might indicate an energetic burden of entanglement and stranding. Six of the healthy leatherbacks were sampled twice, at ~25 and ~50 min after the time of first disturbance. In all six individuals, corticosterone was higher in the later sample (earlier sample, mean 2.74 +/- 0.88 ng/ml, median 2.61 ng/ml; later sample, mean 5.43 +/- 1.29 ng/ml, median 5.38 ng/ml), indicating that capture and handling elicit an adrenal stress response in this species. However, the corticosterone elevation after capture appeared relatively mild compared with the corticosterone concentrations of the entangled and stranded turtles. The findings suggest that capture and handling using the protocols described (e.g. capture duration <1 h) might represent only a mild stressor, whereas entanglement and stranding might represent moderate to severe stressors. PMID- 27413535 TI - The association between generalized joint hypermobility and active horizontal shoulder abduction in 10-15 year old competitive swimmers. AB - BACKGROUND: Increased shoulder mobility and Generalised Joint Hypermobility (GJH) are assumed to be predisposing risk factors for shoulder injuries. The association between GJH and shoulder mobility among competitive swimmers is unknown. The aim was to study the association between GJH and active horizontal shoulder abduction (AHSA) in young, competitive swimmers and to describe normative values of AHSA in this group. METHODS: In total, 92 swimmers (10-15 years) without shoulder pain participated. GJH was evaluated with the Beighton Tests (BT) for joint hypermobility. Shoulder mobility was measured as maximum AHSA. A multiple regression model was used to assess associations between GJH and AHSA. RESULTS: Overall, positive associations were found between GJH and AHSA. An increase of BT score was associated with an increase of AHSA, seen as an increased AHSA of 3.9 degrees , 5.7 degrees and 7.9 degrees by BT cut off points >=5/9, >=6/9 and >=7/9, respectively. Normative values for AHSA ranged from 40 degrees to 52 degrees , depending on age. CONCLUSIONS: Positive associations were found between GJH and AHSA, as maximum AHSA range increased with increasing BT scores. Due to lack of shoulder mobility tests in the BT scoring system, the AHSA test seems to be a promising supplemental test. PMID- 27413534 TI - Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013. AB - Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 +/- 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 +/- 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively. PMID- 27413536 TI - In-field evaluation of clinoptilolite feeding efficacy on the reduction of milk aflatoxin M1 concentration in dairy cattle. AB - BACKGROUND: Clinoptilolite is a natural zeolite with high adsorption capacity for polar mycotoxins such as aflatoxins. The efficacy of clinoptilolite in ameliorating the toxic effects of aflatoxicosis has been proven in monogastric animals, but there is no such evidence for ruminants. The aim of this study was to evaluate, under field conditions, whether the dietary administration of clinoptilolite in dairy cows could reduce the concentration of aflatoxin M1 (AFM1) in bulk-tank milk, in farms with higher than or close to 0.05 MUg/kg of milk (European maximum allowed residual level). An objective of the present study was also to investigate the effect of particle size of clinoptilolite on aflatoxin binding. METHODS: Fifteen commercial Greek dairy herds with AFM1 concentrations in bulk tank milk >=0.05 MUg/kg were selected. Bulk tank milk AFM1 was determined prior to the onset and on day 7 of the experiment. Clinoptilolite was added in the total mixed rations of all farms at the rate of 200 g per animal per day, throughout this period. Two different particle sizes of clinoptilolite were used; less than 0.15 mm in 9 farms (LC group) and less than 0.8 mm in 6 farms (HC group). RESULTS: Clinoptilolite administration significantly reduced AFM1 concentrations in milk in all farms tested at an average rate of 56.2 % (SD: 15.11). The mean milk AFM1 concentration recorded on Day 7 was significantly (P < 0.001) lower compared to that of Day 0 (0.036 +/- 0.0061 vs. 0.078 +/- 0.0074 MUg/kg). In LC group farms the reduction of milk AFM1 concentration was significantly higher than HC group farms (0.046 +/- 0.0074 vs. 0.036 +/- 0.0061 MUg/kg, P = 0.002). As indicated by the Pearson correlation, there was a significant and strong linear correlation among the milk AFM1 concentrations on Days 0 and 7 (R = 0.95, P < 0.001). CONCLUSIONS: Dietary administration of clinoptilolite, especially of smallest particle size, at the rate of 200 g per cow per day can effectively reduce milk AFM1 concentration in dairy cattle and can be used as a preventive measure for the amelioration of the risks associated with the presence of aflatoxins in the milk of dairy cows. PMID- 27413537 TI - Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients. AB - BACKGROUND: Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We hypothesized that the measurement of leucine disposal during a hyperinsulinemic- euglycemic-euaminoacidemic clamp (HEAC) procedure would accurately measure the sensitivity to insulin for its actions on concomitant carbohydrate and protein metabolism in MHD patients. METHODS: We examined 35 MHD patients and 17 control subjects with normal kidney function by hyperinsulinemic-euglycemic clamp (HEGC) followed by HEAC clamp procedure to obtain leucine disposal rate (LDR) along with isotope tracer methodology to assess whole body protein turnover. RESULTS: The glucose disposal rate (GDR) by HEGC was 5.1 +/- 2.1 mg/kg/min for the MHD patients compared to 6.3 +/- 3.9 mg/kg/min for the controls (p = 0.38). The LDR during HEAC was 0.09 +/- 0.03 mg/kg/min for the MHD patients compared to 0.11 +/- 0.05 mg/kg/min for the controls (p = 0.009). The LDR level was correlated with whole body protein synthesis (r = 0.25; p = 0.08), with whole body protein breakdown (r = -0.38 p = 0.01) and net protein balance (r = 0.85; p < 0.001) in the overall study population. Correlations remained significant in subgroup analysis. The GDR derived by HEGC and LDR correlated well in the controls (r = 0.79, p < 0.001), but less so in the MHD patients (r = 0.58, p < 0.001). CONCLUSIONS: Leucine disposal rate reliably measures amino acid utilization in MHD patients and controls in response to high dose insulin. PMID- 27413538 TI - Prognostic value of systolic short-term blood pressure variability in systolic heart failure. AB - BACKGROUND: Traditional cardiovascular risk factors in the general population are usually correlated to a better prognosis in patients with chronic heart failure (HF). Most of the studies show that blood pressure variability (BPV) has noxious effect on general population but data are missing for patients with systolic HF. The aim of this study was to assess the prognostic impact of short-term blood pressure variability (BPV) in systolic HF. METHODS AND RESULTS: We retrospectively studied 288 patients (60 +/- 12 years-old; 79 % male) referred to our tertiary center of HF for the management of their systolic HF (left ventricular ejection fraction was 28 +/- 9 %). All patients underwent ambulatory blood pressure monitoring (systolic BP: 110 +/- 15; diastolic BP: 68 +/- 10 and pulse pressure: 42 +/- 11 mmHg) and the prognostic impact of BPV was collected with a mean follow-up of 4.4 +/- 3.1 years. Twenty-five (9 %) patients were missing for follow-up. Among the others patients, 70 (27 %) cardiovascular events (cardiac deaths: 24 %; heart transplantation: 2 %) were recorded. By multivariate analysis BPV daytime (OR = 0.963, p = 0.033) and severe NYHA class (OR = 5.2, p < 0.0001) were found as independent predictors of cardiac event. Patients with a systolic daytime BPV under a cut-off value of 19 mmHg had the poorest prognosis with an OR for cumulative events of 1.65 (IC95 % 1.1-2.7; p < 0.04). CONCLUSION: BPV is simple tool and a predictor of cardiac events in patients with systolic HF. PMID- 27413539 TI - Current Treatment Approaches to HCC with a Special Consideration to Transplantation. AB - Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients. PMID- 27413541 TI - iStent(r) Trabecular Microbypass Stent: An Update. AB - Due to the high rates of complications and failure experienced with current glaucoma procedures, there is a continuous search for a safer and more effective glaucoma surgery. A new class of procedures termed minimally invasive glaucoma surgeries (MIGS) aim to fill this void by offering an alternative method of IOP reduction associated with markedly reduced complication rates and shorter recovery times. The iStent, a trabecular microbypass stent, is a MIGS device that has quickly gained popularity. The device allows aqueous humor to directly drain from the anterior chamber into Schlemm's canal by bypassing an obstructed trabecular meshwork. This review examines publications about the iStent, focusing on the device's efficacy, safety, and cost when a single iStent or multiple iStents are implanted in combination with cataract surgery or as a solo procedure. Current data suggest that the iStent is a safe and effective tool in the management of mild-to-moderate glaucoma, notable for its limited complications and absence of serious adverse events following implantation. As valuable experience is gained performing ab interno MIGS, increasing familiarity with angle anatomy and iStent placement, and as newer stent designs are developed, there is promise of continual improvement in the surgical management of glaucoma. PMID- 27413540 TI - Evaluation of the Safety and Effectiveness of Intense Pulsed Light in the Treatment of Meibomian Gland Dysfunction. AB - Purpose. This study aims to explore the safety and efficacy of a novel treatment intense pulsed light (IPL) in MGD eyes. Methods. This study is a prospective and open label study. Forty eyes of 40 MGD patients were recruited in the study and received 4 consecutive IPL treatments on day 1, day 15, day 45, and day 75. Ten ocular surface symptoms were evaluated with a subjective face score at every visit. Best spectacle corrected visual acuity, intraocular pressure (IOP), conjunctival injection, upper and lower tear meniscus height (TMH), tear break-up time (TBUT), corneal staining, lid margin and meibomian gland assessments, and meibography were also recorded at every visit, as well as the adverse effects on the eye and ocular surface. Results. Significant improvements were observed in single and total ocular surface symptom scores, TBUT, and conjunctival injection at all the visits after the initial IPL treatment (P < 0.05). Compared to baseline, the signs of eyelid margin, meibomian gland secretion quality, and expressibility were significantly improved at every visit after treatments. There was no regional and systemic threat observed in any patient. Conclusion. Intense pulsed light (IPL) therapy is a safe and efficient treatment in relieving symptoms and signs of MGD eyes. PMID- 27413542 TI - Computational Simulation of Scleral Buckling Surgery for Rhegmatogenous Retinal Detachment: On the Effect of the Band Size on the Myopization. AB - A finite element model (FE) of the eye including cornea, sclera, crystalline lens, and ciliary body was created to analyze the influence of the silicone encircling bandwidth and the tightness degree on the myopia induced by scleral buckling (SB) procedure for rhegmatogenous retinal detachment. Intraocular pressure (IOP) was applied to the reference geometry of the FE model and then SB surgery was simulated with encircling bandwidths of 1, 2, and 2.5 mm. Different levels of tightening and three values of IOP were applied. The anterior segment resulted as unaffected by the surgery. The highest value of Cauchy stress appeared in the surroundings of the implant, whereas no increment of stress was observed either in anterior segment or in the optic nerve head. The initial IOP did not appear to play any role in the induced myopia. The wider the band, the greater the induced myopia: 0.44, 0.88, and 1.07 diopters (D) for the 1, 2, and 2.5 mm bandwidth, respectively. Therefore, patients become more myopic with a wider encircling element. The proposed simulations allow determining the effect of the bandwidth or the tightness degree on the axial lengthening, thus predicting the myopic increment caused by the encircling surgery. PMID- 27413543 TI - Optical Coherence Tomography Parameters in Morbidly Obese Patients Who Underwent Laparoscopic Sleeve Gastrectomy. AB - Purpose. To investigate changes in optical coherence tomography parameters in morbidly obese patients who had undergone laparoscopic sleeve gastrectomy (LSG). Methods. A total of 41 eyes of 41 morbidly obese patients (BMI >= 40) who had undergone LSG were included in study. The topographic optic disc parameters, central macular thickness (CMT), total macular volume (TMV), and retinal ganglion cell layer (RGCL) were measured by spectral-domain optical coherence tomography (SD-OCT). Subfoveal choroidal thickness (SFCT) was measured by enhanced deep imaging-optical coherence tomography (EDI-OCT). Results. The mean CMT was 237.4 +/- 24.5 MUm, 239.3 +/- 24.1 MUm, and 240.4 +/- 24.5 MUm preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p < 0.01). The mean TMV was 9.88 +/- 0.52 mm(3), 9.96 +/- 0.56 mm(3), and 9.99 +/- 0.56 mm(3) preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p < 0.01). The mean RGCL was 81.2 +/- 6.5 MUm, 82.7 +/- 6.6 MUm, and 82.9 +/- 6.5 MUm preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p < 0.01). The mean SFCT was 309.8 +/- 71.8 MUm, 331.0 +/- 81.4 MUm, and 352.7 +/- 81.4 MUm preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p < 0.01). No statistically significant differences were found between the preoperative values and 3- and 6-month postoperative values in rim area (p = 0.34), disc area (p = 0.64), vertical cup/disc ratio (p = 0.39), cup volume (p = 0.08), or retinal nerve fiber layer (p = 0.90). Conclusions. Morbidly obese patients who undergo LSG experience a statistically significant increase in CMT, TMV, SFCT, and RGCL at 3 months and 6 months after surgery. PMID- 27413544 TI - Relationship between Peeled Internal Limiting Membrane Area and Anatomic Outcomes following Macular Hole Surgery: A Quantitative Analysis. AB - Purpose. To quantitatively evaluate the effects of peeled internal limiting membrane (ILM) area and anatomic outcomes following macular hole surgery using spectral domain optical coherence tomography (SD-OCT). Methods. Forty-one eyes in 37 consecutive patients with idiopathic, Gass stage 3-4 macular hole (MH) were enrolled in this retrospective comparative study. All patients were divided into 2 groups according to anatomic success or failure. Basal MH diameter, peeled ILM area, and MH height were calculated using SD-OCT. Other prognostic parameters, including age, stage, preoperative BCVA, and symptom duration were also assessed. Results. Thirty-two cases were classified as anatomic success, and 9 cases were classified as anatomic failure. Peeled ILM area was significantly wider and MH basal diameter was significantly less in the anatomic success group (p = 0.024 and 0.032, resp.). Other parameters did not demonstrate statistical significance. Conclusion. The findings of the present study show that the peeled ILM area can affect the anatomic outcomes of MH surgery. PMID- 27413545 TI - Causative Microorganisms of Infectious Endophthalmitis: A 5-Year Retrospective Study. AB - This study aimed to identify the microbial etiology of infectious endophthalmitis and to determine the antibacterial susceptibilities of bacterial isolates at an eye hospital in South China. A retrospective analysis was carried out on 330 patients with clinically diagnosed infectious endophthalmitis who underwent microbiological evaluation from January 2010 to December 2014. Of the 330 patients, 193 patients (58.5%) had posttraumatic endophthalmitis, 67 patients (20.3%) had postoperative endophthalmitis, 61 patients (18.5%) had endogenous endophthalmitis, and 9 patients (2.7%) had postcorneal infective endophthalmitis. Of the 105 cases (31.8%) of culture-positive endophthalmitis, 79 cases (75.2%) had bacterial growth and 26 cases (24.8%) had fungal growth. In posttraumatic endophthalmitis, Gram-positive bacteria were the predominant species, followed by Gram-negative bacteria and fungi. In endogenous endophthalmitis, Gram-negative bacteria were the predominant species, followed by fungi and Gram-positive bacteria. In postsurgical endophthalmitis, all infections were bacterial. However, in postcorneal infective endophthalmitis, all infections were fungal. Overall, levofloxacin showed the highest activity against bacterial isolates. There was a significant difference in the susceptibility to tobramycin between the isolates from posttraumatic and postoperative endophthalmitis (p < 0.05). The results of this study identify the microbial spectrum of infectious endophthalmitis in this clinical setting. PMID- 27413546 TI - Changes in Weight Loss, Health Behaviors, and Intentions among 400 Participants Who Dropped out from an Insurance-Sponsored, Community-Based Weight Management Program. AB - The majority of weight management research is based on data from randomized controlled studies conducted in clinical settings. As these findings are translated into community-based settings, additional research is needed to understand patterns of lifestyle change and dropout. The purpose of this study was to examine reasons for and consequences associated with dropout (or removal) from an insurance-funded weight management program. Using a mixed methods approach with objectively measured changes in body weight and attendance along with quantitative and qualitative survey data, patterns of intention and behavior change were explored. The results from a sample of 400 respondents support the idea that there are both positive and negative consequences of program participation. Overall, 1 in 5 respondents lost a clinically significant amount of weight during the program (>5% of baseline body weight) and 1 in 3 experienced a positive consequence, while only 6% expressed a negative outcome of participation. Additionally, nearly 90% of all of the consequences that emerged from the data were positive. Attitude change was a major theme, including positive health intentions, perceived success, learning skills, and new appreciation of exercise. PMID- 27413547 TI - Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin. AB - Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients. Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls. Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS]; p < 0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56-193.32; p = 0.007]; OR = 16 [95% CI, 1.69 151.11; p = 0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06-37.44; p = 0.003]; MH OR = 5.76 [95% CI, 1.64-20.24; p = 0.006]). Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin. PMID- 27413548 TI - The Need for Pediatric Formulations to Treat Children with HIV. AB - Over 3.2 million children worldwide are infected with HIV, but only 24% of these children receive antiretroviral therapy (ART). ART adherence among children is a crucial part of managing human-immunodeficiency virus (HIV) infection and extending the life and health of infected children. Important causes of poor adherence are formulation- and regimen-specific properties, including poor palatability, large pill burden, short dosing intervals, and the complex storage and transportation of drugs. This review aims to summarize the various regimen- and formulation-based barriers to ART adherence among children to support the need for new and innovative pediatric formulations for antiretroviral therapy (ART). Detailing the arguments both for and against investing in the development of pediatric HIV medications, as well as highlighting recent advances in pediatric ART formulation research, provides a synopsis of the current data related to pediatric ART formulations and adherence. PMID- 27413549 TI - What Do Parents Think about Chromosomal Microarray Testing? A Qualitative Report from Parents of Children with Autism Spectrum Disorders. AB - Background. Chromosomal Microarray Analysis (CMA) is increasingly utilized to detect copy number variants among children and families affected with autism spectrum disorders (ASD). However, CMA is controversial due to possible ambiguous test findings, uncertain clinical implications, and other social and legal issues related to the test. Methods. Participants were parents of children with ASD residing in the North Eastern region of North Carolina, USA. We conducted individual, face-to-face interviews with 45 parents and inquired about their perceptions of CMA. Results. Three major themes dominated parents' perceptions of CMA. None of the parents had ever heard of the test before and the majority of the parents postulated positive attitudes toward the test. Parents' motivations in undergoing the test were attributed to finding a potential cause of ASD, to being better prepared for having another affected child, and to helping with future reproductive decisions. Perceived barriers included the cost of testing, risk/pain of CMA testing, and fear of test results. Conclusion. This study contributes to the understanding of psychosocial aspects and cultural influences towards adoption of genetic testing for ASD in clinical practice. Genetic education can aid informed decision-making related to CMA genetic testing among parents of children with ASD. PMID- 27413550 TI - Symptoms and Etiological Attribution: A Cross-Sectional Study in Mexican Outpatients with Psychosis and Their Relatives. AB - This cross-sectional study aimed at identifying the most common attributions of their mental disorder in a Mexican patients who have experienced psychosis and their relatives and exploring how having experienced or not characteristic psychotic symptoms and their present clinical status might affect their etiological attributions. Past and current symptom profiles of 66 patients were as assessed with the SCID-I (Structured Clinical Interview for DSM-IV Axis I Disorders) and the PANSS (Positive and Negative Syndrome Scale), respectively. The etiological attribution of psychosis of patients (n = 62) and the relatives (n = 65) was assessed with the Angermeyer and Klusmann scale comprising 30 items into five categories: biology, personality, family, society, and esoteric. Patients and relatives attribute psychosis mainly to social factors. Relatives' attributions were not influenced by clinical profile of patients, whereas in the case of patients it was only current clinical status that showed a difference, with those in nonremission scoring higher personality and family factors. Acknowledging patients' and relatives' beliefs about mental disorders at onset and later on is particularly important in psychosis, a mental condition with severe and/or persistent symptoms, in order to promote better involvement in treatment and in consequence efficacy and recovery. PMID- 27413551 TI - Breast Cancer in Africa: Limitations and Opportunities for Application of Genomic Medicine. AB - As genomic medicine gains clinical applicability across a spectrum of diseases, insufficient application in low-income settings stands to increase health disparity. Breast cancer screening, diagnosis, and treatment have benefited greatly from genomic medicine in high-income settings. As breast cancer is a leading cause of both cancer incidence and mortality in Africa, attention and resources must be applied to research and clinical initiatives to integrate genomic medicine into breast cancer care. In terms of research, there is a paucity of investigations into genetic determinants of breast cancer specific to African populations, despite consensus in the literature that predisposition and susceptibility genes vary between populations. Therefore, we need targeted strengthening of existing research efforts and support of new initiatives. Results will improve clinical care through screening and diagnosis with genetic testing specific to breast cancer in African populations. Clinically, genomic medicine can provide information capable of improving resource allocation to the population which most stands to benefit from increased screening or tailored treatment modalities. In situations where mammography or chemotherapy options are limited, this information will allow for the greatest impact. Implementation of genomic medicine will face numerous systemic barriers but is essential to improve breast cancer outcomes and survival. PMID- 27413552 TI - Promoter Methylation Status of Breast Cancer Susceptibility Gene 1 and 17 Beta Hydroxysteroid Dehydrogenase Type 1 Gene in Sporadic Breast Cancer Patients. AB - Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17betaHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17betaHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (p < 0.001). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype "luminal A" (p = 0.048, p = 0.042, p = 0.007, and p = 0.049, resp.). Methylation of BRCA1 and 17betaHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17betaHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies. PMID- 27413553 TI - Refreshing Sleep and Sleep Continuity Determine Perceived Sleep Quality. AB - Sleep quality is a construct often measured, employed as an outcome criterion for therapeutic success, but never defined. In two studies we examined appraised good and poor sleep quality in three groups: a control group, individuals with obstructive sleep apnea, and those with insomnia disorder. In Study 1 we used qualitative methodology to examine good and poor sleep quality in 121 individuals. In Study 2 we examined sleep quality in 171 individuals who had not participated in Study 1 and evaluated correlates and predictors of sleep quality. Across all six samples and both qualitative and quantitative methodologies, the daytime experience of feeling refreshed (nonrefreshed) in the morning and the nighttime experience of good (impaired) sleep continuity characterized perceived good and poor sleep. Our results clarify sleep quality as a construct and identify refreshing sleep and sleep continuity as potential clinical and research outcome measures. PMID- 27413554 TI - Frequency-Dependent Neural Activity in Patients with Unilateral Vascular Pulsatile Tinnitus. AB - Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown that neurological changes are important findings in vascular pulsatile tinnitus (PT) patients. Here, we utilized rs-fMRI to measure the amplitude of low frequency fluctuations (ALFF) in forty patients with unilateral PT and forty age , gender-, and education-matched normal control subjects. Two different frequency bands (slow-4, 0.027-0.073 Hz, and slow-5, 0.010-0.027 Hz, which are more sensitive to subcortical and cortical neurological signal changes, resp.) were analyzed to examine the intrinsic brain activity in detail. Compared to controls, PT patients had increased ALFF values mainly in the PCu, bilateral IPL (inferior parietal lobule), left IFG (inferior frontal gyrus), and right IFG/anterior insula and decreased ALFF values in the multiple occipital areas including bilateral middle-inferior occipital lobe. For the differences of the two frequency bands, widespread ALFF differences were observed. The ALFF abnormalities in aMPFC/ACC, PCu, right IPL, and some regions of occipital and parietal cortices were greater in the slow-5 band compared to the slow-4 band. Additionally, the THI score of PT patients was positively correlated with changes in slow-5 and slow-4 band in PCu. Pulsatile tinnitus is a disease affecting the neurological activities of multiple brain regions. Slow-5 band is more sensitive in detecting the alternations. Our results also indicated the importance of pathophysiological investigations in patients with pulsatile tinnitus in the future. PMID- 27413555 TI - Hemodynamic Response of the Supplementary Motor Area during Locomotor Tasks with Upright versus Horizontal Postures in Humans. AB - To understand cortical mechanisms related to truncal posture control during human locomotion, we investigated hemodynamic responses in the supplementary motor area (SMA) with quadrupedal and bipedal gaits using functional near-infrared spectroscopy in 10 healthy adults. The subjects performed three locomotor tasks where the degree of postural instability varied biomechanically, namely, hand knee quadrupedal crawling (HKQuad task), upright quadrupedalism using bilateral Lofstrand crutches (UpQuad task), and typical upright bipedalism (UpBi task), on a treadmill. We measured the concentration of oxygenated hemoglobin (oxy-Hb) during the tasks. The oxy-Hb significantly decreased in the SMA during the HKQuad task, whereas it increased during the UpQuad task. No significant responses were observed during the UpBi task. Based on the degree of oxy-Hb responses, we ranked these locomotor tasks as UpQuad > UpBi > HKQuad. The order of the different tasks did not correspond with postural instability of the tasks. However, qualitative inspection of oxy-Hb time courses showed that oxy-Hb waveform patterns differed between upright posture tasks (peak-plateau-trough pattern for the UpQuad and UpBi tasks) and horizontal posture task (downhill pattern for the HKQuad task). Thus, the SMA may contribute to the control of truncal posture accompanying locomotor movements in humans. PMID- 27413556 TI - Functional Connectivity Analysis of NIRS Data under Rubber Hand Illusion to Find a Biomarker of Sense of Ownership. AB - The self-identification, which is called sense of ownership, has been researched through methodology of rubber hand illusion (RHI) because of its simple setup. Although studies with neuroimaging technique, such as fMRI, revealed that several brain areas are associated with the sense of ownership, near-infrared spectroscopy (NIRS) has not yet been utilized. Here we introduced an automated setup to induce RHI, measured the brain activity during the RHI with NIRS, and analyzed the functional connectivity so as to understand dynamical brain relationship regarding the sense of ownership. The connectivity was evaluated by multivariate Granger causality. In this experiment, the peaks of oxy-Hb on right frontal and right motor related areas during the illusion were significantly higher compared with those during the nonillusion. Furthermore, by analyzing the NIRS recordings, we found a reliable connectivity from the frontal to the motor related areas during the illusion. This finding suggests that frontal cortex and motor related areas communicate with each other when the sense of ownership is induced. The result suggests that the sense of ownership is related to neural mechanism underlying human motor control, and it would be determining whether motor learning (i.e., neural plasticity) will occur. Thus RHI with the functional connectivity analysis will become an appropriate biomarker for neurorehabilitation. PMID- 27413557 TI - A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD. AB - Posttraumatic stress disorder (PTSD) is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF) is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met), has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n = 257) screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n = 3625). A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future. PMID- 27413558 TI - Intermittent Fever, Progressive Weight Gain, and Personality Changes in a Five Year-Old Girl: Unusual Paraneoplastic Syndrome due to Presacral Ganglioneuroma. AB - Ganglioneuromas are rare tumors in the neuroblastoma group. Paraneoplastic syndrome (PNS) due to presacral ganglioneuromas was hardly reported in previous literature. Here, we reported that a case of a 5-year-old girl with a presacral ganglioneuroma presented with PNS, who presented with intermittent fever, progressive weight gain, and personality changes. Our report revealed intermittent fever, progressive weight gain, and personality changes may represent rare paraneoplastic syndromes in ganglioneuromas. PMID- 27413559 TI - Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm. AB - Adrenocortical oncocytic neoplasms (oncocytomas) are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol) and androgens (androstenedione and DHEAS), a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing's syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline) according to the Lin-Weiss-Bisceglia criteria. PMID- 27413560 TI - Organizing Pneumonia in a Patient with Quiescent Crohn's Disease. AB - A 64-year-old man with Crohn's disease (CD) was admitted to our hospital due to moderate risk of pneumonia while receiving scheduled adalimumab maintenance therapy. Symptoms remained virtually unchanged following administration of antibiotics. A final diagnosis of organizing pneumonia (OP) was made based on findings of intra-alveolar buds of granulation tissue and fibrous thickening of the alveolar walls on pathological examination and patchy consolidations and ground glass opacities on computed tomography. Immediate administration of prednisolone provided rapid, sustained improvement. Although a rare complication, OP is a pulmonary manifestation that requires attention in CD patients. PMID- 27413561 TI - Spontaneous Heterotopic Pregnancy: Dual Case Report and Review of Literature. AB - Introduction. Heterotopic pregnancy is a rare complication usually seen in populations at risk for ectopic pregnancy or those undergoing fertility treatments. It is a potentially dangerous condition occurring in only 1 in 30,000 spontaneous pregnancies. With the advent of Assisted Reproduction Techniques (ART) and ovulation induction, the overall incidence of heterotopic pregnancy has risen to approximately 1 in 3,900 pregnancies. Other risk factors include a history of pelvic inflammatory disease (PID), tubal damage, pelvic surgery, uterine Mullerian abnormalities, and prior tubal surgery. Heterotopic pregnancy is a potentially fatal condition, rarely occurring in natural conception cycles. Most commonly, heterotopic pregnancy is diagnosed at the time of rupture when surgical management is required. Case. This paper represents two cases of heterotopic pregnancies as well as a literature review. Conclusion. Heterotopic pregnancy should be suspected in patients with an adnexal mass, even in the absence of risk factors. Clinicians must be alert to the fact that confirming an intrauterine pregnancy clinically or by ultrasound does not exclude the coexistence of an ectopic pregnancy. A high index of suspicion in women is needed for early and timely diagnosis, and management with laparotomy or laparoscopy can result in a favorable and successful obstetrical outcome. PMID- 27413562 TI - Clinical-Radiological Correlation of Retained Silicone Sponge Presenting as Orbital Inflammation. AB - A 32-year-old female who underwent scleral buckle removal presented 5 weeks postoperatively with a red, fluctuant subconjunctival mass. CT scan identified an irregularly bordered, hypoattenuated lesion next to the globe with the density of air. Ophthalmic plastic and reconstructive surgeons were consulted to evaluate orbital cellulitis with intraorbital gas, at which point it was deemed that the hypoattenuated mass was likely a retained sponge element based on its radiological features. Additional surgical exploration identified the retained silicone sponge. This clinical photographic-radiological correlation of retained silicone sponges presenting as orbital inflammation reminds surgeons to meticulously explant buckle material. PMID- 27413563 TI - Combined DSEK and Transconjunctival Pars Plana Vitrectomy. AB - We report here three patients who underwent combined Descemet's stripping with endothelial keratoplasty and transconjunctival pars plana vitrectomy for bullous keratopathy and posterior segment pathology. A surgical technique and case histories are described. Anatomic and visual outcomes of combined Descemet's stripping with endothelial keratoplasty and vitrectomy were excellent. Our experience provides technical guidelines and limitations. The combined minimally invasive techniques allow for rapid anatomical recovery and return of function and visual acuity in a single sitting. PMID- 27413564 TI - Scoliosis Surgery in Cystic Fibrosis: Surgical Considerations and the Multidisciplinary Approach of a Rare Case. AB - Spinal deformity in patients with cystic fibrosis (CF) is usually mild requiring no treatment. These patients are rarely considered as surgical candidates for scoliosis correction, as the pulmonary condition and other comorbidities increase the risk of general anaesthesia and recovery. This paper reviews all the literature up to date with regard to scoliosis in patients with CF and reports this unique case of a 14-year-old Caucasian girl with progressive scoliosis, who was treated surgically at the age of 17. She underwent a posterior spinal fusion T2-L3 with the use of unilateral segmental instrumentation. Preoperative workup included respiratory, cardiac, anaesthetic, endocrine, and dietician reviews, as well as bone density optimisation with zoledronic acid and prophylactic antibiotics. Surgical time was 150 minutes and intraoperative blood loss was 47% of total blood volume. Postoperative intensive care included noninvasive ventilation, antibiotic cover, pain management, chest physiotherapy, pancreatic enzyme supplementation, and nutritional support. She was discharged on day 9. At follow-up she had a good cosmetic outcome, no complaints of her back, and stable respiratory function. Multidisciplinary perioperative care and meticulous surgical technique may reduce the associated risks of major surgery in CF patients, while achieving adequate deformity correction and a good functional outcome. PMID- 27413565 TI - Lower Limb Reconstruction with Tibia Allograft after Resection of Giant Aneurysmal Bone Cyst. AB - Aneurysmal bone cysts (ABCs) are benign, expansible, nonneoplastic lesions of the bone, characterized by channels of blood and spaces separated by fibrous septa, which occur in young patients and, occasionally, with aggressive behavior. Giant ABC is an uncommon pathological lesion and can be challenging because of the destructive effect of the cyst on the bones and the pressure on the nearby structures, especially on weight-bearing bones. In this scenario, en bloc resection is the mainstay treatment and often demands complex reconstructions. This paper reports a difficult case of an unusual giant aneurysmal bone cyst, which required extensive resection and a knee fusion like reconstruction with tibia allograft. PMID- 27413566 TI - Symmetric Lipomatosis Arising in the Tongue Presenting as Macroglossia and Articulatory Disorder. AB - Symmetric lipomatosis is definitively characterized by symmetric, tumorous lipomatous proliferation of adipose tissue that often develops in the head and neck, shoulders, and upper trunk. However, in the oral region, symmetric lipomatosis of the tongue (SLT) is an extremely rare condition related to generalized lipidosis that is often caused by chronic alcoholism. It is characterized by multiple symmetric lipomatous nodules and diffuse bilateral swelling located within the tongue. We report an extremely rare case of SLT arising in an 80-year-old man with a long history of alcoholic liver cirrhosis. He exhibited multiple soft nodular protrusions on the bilateral margin of the tongue presenting as macroglossia for years. Although MR imaging showed multiple fatty masses on both sides of the tongue, there was no elevated tumor mass on the bilateral margin. The patient underwent bilateral partial glossectomy under general anesthesia. Histopathologically, the resected tumor exhibited diffuse infiltration with mature adipose tissue lacking a fibrous capsule. Due to the lipidosis and the unusual presentation of multiple lesions, the lesion was ultimately diagnosed as SLT. At present, after surgery, the patient wears a full denture and is in excellent condition, with no sign of recurrence, improved QOL, and recovery of masticatory, articulatory, and speech intelligibility functions. PMID- 27413568 TI - A Case of Tuberculous Meningitis with Tuberculoma in Nonimmunocompromised Immigrant. AB - We present a case of tuberculous (TB) meningitis in nonimmunocompromised immigrant worker who initially presented with headache and later with generalized tonic clonic seizures and disseminated tuberculosis. PMID- 27413567 TI - Cooccurrence of Postural Orthostatic Tachycardia Syndrome with Two Different Clinical Entities. AB - Postural orthostatic tachycardia syndrome (POTS) is an abnormal heart rate response to a positional change. Several potential mechanisms for pathophysiology of POTS are defined. This syndrome can coexist with different clinical situations. In our report, the first case was a 13-year-old female who has been followed up for diagnosis of homocystinuria. She was admitted to our outpatient clinic with complaints of dizziness after suddenly moving from supine to upright position and chest pain after exercise. Tilt table test was performed to evaluate dizziness. According to the tilt table test the patient was diagnosed with POTS. The second case was a 17-year-old female who had been evaluated in different centers with the complaints of fainting, bruising, redness, and swelling on the hands and feet after moving from supine position to upright position during the last 4 years. Postural orthostatic tachycardia syndrome was diagnosed by tilt table test and ivabradine was started. Herein, we aimed to point out the cooccurrence of different clinical entities and POTS. PMID- 27413569 TI - Solitary Spinal Epidural Metastasis from Prostatic Small Cell Carcinoma. AB - Solitary, spinal epidural metastasis (SEM) that is not related to vertebral metastasis is very rare. And solitary SEM from prostatic cancer is rarely found in previously published reports. However, it is clinically significant due to the possibility of neurologic dysfunction, and it can be assessed by MRI. In this report, we show a case of solitary SEM arising from prostatic small cell carcinoma detected by MRI. PMID- 27413570 TI - A Case Study of Severe Esophageal Dysmotility following Laparoscopic Sleeve Gastrectomy. AB - Following bariatric surgery, a proportion of patients have been observed to experience reflux, dysphagia, and/or odynophagia. The etiology of this constellation of symptoms has not been systematically studied to date. This case describes a 36-year-old female with severe esophageal dysmotility following LSG. Many treatments had been used over a course of 3 years, and while calcium channel blockers reversed the esophageal dysmotility seen on manometry, significant symptoms of dysphagia persisted. Subsequently, the patient underwent a gastric bypass, which seemed to partially relieve her symptoms. Her dysphagia was no longer considered to be associated with a structural cause but attributed to a "sleeve dysmotility syndrome." Considering the difficulties with managing sleeve dysmotility syndrome, it is reasonable to consider the need for preoperative testing. The question is whether motility studies should be required for all patients planning to undergo a LSG to rule out preexisting esophageal dysmotility and whether conversion to gastric bypass is the preferred method for managing esophageal dysmotility after LSG. PMID- 27413571 TI - Type IV Sacrococcygeal Teratoma Displacing the Urinary Bladder: Unique Magnetic Resonance Imaging. AB - Type IV sacrococcygeal teratoma is a rare pediatric tumor that is confined to the presacral area with no external component. The signs and symptoms often arise due to mass effect and compression of adjacent organs. Urinary retention is an uncommon presenting symptom in these patients. A wide spectrum of imaging findings may be encountered in cases with sacrococcygeal teratoma because of variability of tumor size and components. We hereby present a unique magnetic resonance urography finding in a type IV sacrococcygeal teratoma which caused bladder displacement. A meticulous and complete resection of tumor with special attention to the pelvic plexus led to preservation of normal voiding function and normal bowel function in this patient. PMID- 27413572 TI - A Case of Strangulated Urethral Prolapse in a Premenopausal Adult Female. AB - Urethral prolapse in a premenopausal adult female is exceedingly rare. This paper describes a case of strangulated urethral prolapse presenting as a urethral mass in an unusual demographic and reviews the literature on etiology and management. Only a few cases have occurred in women of reproductive age. The etiology is likely multifactorial. Treatment with surgical excision provides good results in the majority of cases. PMID- 27413573 TI - Ulcerated Scrotal Hemangioma in an 18-Month-Old Male Patient: A Case Report and Review of the Literature. AB - Deep scrotal hemangiomas are rare. Less than 50 case reports have been published. After systematic research of the literature, we found less than 5 cases of ulcerated scrotal hemangioma. The aim of this case report is to illustrate the challenges of scrotal hemangiomas pose and their potential therapies based on the successful surgical treatment of an ulcerated scrotal hemangioma in an 18-month old male patient. PMID- 27413574 TI - Family Dynamics and Personal Strengths among Dementia Caregivers in Argentina. AB - This study examined whether healthier family dynamics were associated with higher personal strengths of resilience, sense of coherence, and optimism among dementia caregivers in Argentina. Caregivers are usually required to assist individuals with dementia, and family members have typically fulfilled that role. Personal strengths such as resilience, sense of coherence, and optimism have been shown to protect caregivers from some of the negative experiences of providing care, though the family-related variables associated with these personal strengths are largely unknown. Hierarchical multiple regressions investigated the extent to which family dynamics variables are associated with each of the caregiver personal strengths after controlling for demographic and caregiver characteristics. A sample of 105 caregivers from Argentina completed a set of questionnaires during a neurologist visit. Family dynamics explained 32% of the variance in resilience and 39% of the variance in sense of coherence. Greater family empathy and decreased family problems were uniquely associated with higher resilience. Greater communication and decreased family problems were uniquely associated with higher sense of coherence. Optimism was not found to be significantly associated with family dynamics. These results suggest that caregiver intervention research focused on the family may help improve caregiver personal strengths in Argentina and other Latin American countries. PMID- 27413576 TI - Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson's Disease. AB - Purpose. The present study aimed to explore the changes of amplitude of low frequency fluctuations (ALFF) at rest in patients with Parkinson's disease (PD). Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6) and dorsolateral prefrontal cortex (BA 9/10). Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease. PMID- 27413575 TI - Chaperone-Mediated Autophagy and Mitochondrial Homeostasis in Parkinson's Disease. AB - Parkinson's disease (PD), a complex neurodegenerative disorder, is pathologically characterized by the formation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial dysfunction is considered to be one of the most important causative mechanisms. In addition, dysfunction of chaperone-mediated autophagy (CMA), one of the lysosomal proteolytic pathways, has been shown to play an important role in the pathogenesis of PD. An exciting and important development is recent finding that CMA and mitochondrial quality control may be linked. This review summarizes the studies revealing the link between autophagy and mitochondrial function. Discussions are focused on the connections between CMA and mitochondrial failure and on the role of MEF2D, a neuronal survival factor, in mediating the regulation of mitochondria in the context of CMA. These new findings highlight the need to further explore the possibility of targeting the MEF2D-mitochondria-CMA network in both understanding the PD pathogenesis and developing novel therapeutic strategies. PMID- 27413578 TI - Superficial temporal artery pseudoaneurysm presenting as a growing, pulsatile, and tender mass. AB - BACKGROUND: Superficial temporal artery (STA) pseudoaneurysms have been reported in the literature since the mid of seventeenth century from Bartholin, however, there is an increasing number of cases, suggesting a diversity of etiological factors. Among these, traumatic events, even of an iatrogenic nature, have been identified as causative factors for nonspontaneous STA pseudoaneurysms. Regional pain and tenderness, troublesome pulsations of the mass, cosmetic concerns as well as the risk of bleeding warrant a thorough evaluation and a definite interventional approach to the condition. CASE DESCRIPTION: A 21-year-old Caucasian male searched medical advice for a growing, tender, and pulsatile mass on his right temple, with isolated and short episodes of lancinating sensations, after sustaining a blunt trauma following a hit with a stick half a year before the admission. Enhanced cranial computed tomography and angiography confirmed the diagnosis of an STA pseudoaneurysm. A direct percutaneous aspiration, as well as ultrasonography, was performed prior to the neurosurgical intervention, with the complete removal of the mass. CONCLUSIONS: STA pseudoaneurysms require a careful evaluation and a conclusive approach in order to avoid the risk of a growing mass and other nonremote complications such as bone erosions and bleeding. Different treatment options are available, including endovascular obliteration and embolization, however, surgical removal after ligation of the afferent and efferent segments of the vessel seem to be highly effective. PMID- 27413579 TI - Improvement of long-term blindness caused by compression from inner-third sphenoid wing meningioma after optic canal decompression: An extremely rare case report. AB - BACKGROUND: There has been no previous case report of a patient whose visual acuity improved after long-term blindness caused by tumor invasion into the optic canal. CASE DESCRIPTION: A 65-year-old Asian woman presented with a 6-month history of blindness caused by a meningioma located on the inner third of the sphenoid ridge. An operation was performed to prevent further tumor invasion into the cavernous sinus and contralateral optic nerve. During surgery, optic canal decompression was performed using an epidural approach. Subtotal removal of the tumor was achieved. Two days after the surgery, her left visual acuity recovered from blindness. CONCLUSION: Normally, long-term blindness caused by optic nerve compression by a brain tumor is regarded as irreversible, and even a surgical excision of the optic nerve is performed in some cases. However, because we experienced a case in which the patient recovered from long-term blindness after optic canal decompression, we believe that this surgical procedure should definitely be considered as an option. PMID- 27413577 TI - Influence of Medication on Fatigue Six Months after Stroke. AB - Poststroke fatigue (PSF) is frequent and affects patients' quality of life. Medication use was hypothesized as being responsible for PSF. Our objective was to evaluate potential relationships between 6-month PSF and medication use at discharge and 6 months after an ischemic stroke. This study is part of STROKDEM, an ongoing longitudinal cohort study, whose main aim is to determine predictors of poststroke dementia. Patients were included within 72 hours after an ischemic stroke and followed up with standardized evaluations. Medication use 7 days and 6 months after stroke was rated, and polypharmacy was defined as the number of categories of treatments received by a patient. PSF was evaluated using the Chalder Fatigue Scale. Medical history, vascular risk factors, depression, anxiety, and sleep disturbances were evaluated. One hundred and fifty-three patients were included: 52.9% presented PSF. PSF at 6 months was not predicted by medication use at discharge nor associated with medication use at month 6. We found severity of PSF to be increased in patients with polypharmacy. Our results suggest that PSF is not a side effect of drugs use, which more reflects presence of disturbances frequently observed after stroke such as depression, anxiety, or sleep disturbances. Clinical study is registered on clinicaltrials.gov (NCT01330160). PMID- 27413580 TI - Free market or socialized medicine for the future of US health care? PMID- 27413581 TI - Postoperative cerebral myiasis: A rare cause of wound dehiscence in developing countries. AB - BACKGROUND: Cerebral myiasis is a rare parasitic disease, especially in postoperative neurological surgery. CASE DESCRIPTION: We report a case of postoperative myiasis in a patient who underwent a craniotomy for resection of metastatic melanoma, evolving with wound dehiscence due to myiasis in the operative wound. CONCLUSION: Myiasis infestation should be a differential diagnosis of surgical wound dehiscence, particularly when the classic signs of inflammation are not present and computed tomography of the brain shows signs suggestive of this disease entity. PMID- 27413583 TI - ASPECT-R-A Tool to Rate the Pragmatic and Explanatory Characteristics of a Clinical Trial Design. AB - OBJECTIVE: Clinical and observational trials can be broadly categorized into having explanatory or pragmatic approaches with specific trial designs located somewhere along this spectrum. Two 10-domain instruments, the PRECIS and Pragmascope, have been developed to facilitate clinical trial design within a framework that is either more explanatory or pragmatic. DESIGN: We have adapted the PRECIS and Pragmascope instruments to permit both design support and post-hoc evaluation of clinical trials and to improve consistency of use and interpretation across raters. This adapted instrument, A Study Pragmatic Explanatory Characterization Tool-Rating-or ASPECT-R-is described. RESULTS: Adaption of the PRECIS and Pragmascope instruments included reducing the 10 original domains to six. Each of the six ASPECT-R domains has a definition of domain terminology and detailed descriptive anchors. The domains are rated from 0 to 6, where 0 is considered extremely explanatory and 6 extremely pragmatic. Using an Excel(r)-based file with cover page cells for entry of the study objective(s) and study population of interest, the ASPECT-R instrument has individual domain-related worksheets where the user rates each of the six domains. Each of the six domain worksheets has a section provided for the user to summarize and record the rationale for their domain scoring. Each domain worksheet page also contains a radar graph that auto-populates each of the domain ratings as the user completes these ratings. CONCLUSION: This new tool, ASPECT-R, should provide a reliable, objective way to rate studies along the explanatory pragmatic spectrum that will better support trial design and facilitate interpretation of completed trials. The complete ASPECT-R tool and guide materials can be accessed online by clicking or visiting this link: http://innovationscns.com/aspect-r-tool-and-training-materials/. PMID- 27413582 TI - Erectile Dysfunction in Individuals with Neurologic Disability: A Hospital-based Cross-sectional Study. AB - OBJECTIVE: Neurogenic erectile dysfunction can be broadly defined as an inability to sustain or maintain a penile erection due to neurologic impairment. Sexual problems can occur due to any lesion affecting the central and peripheral nervous system. The aim of this study was to evaluate the prevalence and causes of erectile dysfunction in a group of hospital inpatients suffering from neurologic disorders. METHODS: Three-hundred and twenty six male patients admitted to the Neurorehabilitation Unit of IRCCS Centro Neurolesi "Bonino-Pulejo" in Messina Italy from March 2012 to June 2013 were screened for erectile dysfunction using the International Index of Erectile Function questionnaire. The patients who reported erectile dysfuntion underwent vascular, neurophysiological, and hormonal testing, and were divided into two groups according to their lesion sites: G1 (lesions above the S2-S4 center) and G2 (lesions below the S2-S4 center). RESULTS: Of the 326 admitted patients, 126 patients (38.6%), mean age of 54.56+/ 11.74 years (age range 27-82 years), were affected by erectile dysfunction (i.e., scored <=21). A statistically significant correlation between International Index of Erectile Function questionnaire scores and location of the neurologic lesions was observed in G2 (r=0.22) with an increased risk of erectile dysfuntion of around 2:1 (odds ratio=1.87) without influences related to aging. CONCLUSION: The occurence of erectile dysfunction is significantly more prevalent among neurologically disabled men, particularly those with lesions below S2-S4, than among men without neurologic disability. Considering the prevalence of erectile dysfunction among neurologically disabled men, sexual functioning should be regularly evaluated during acute and long-term rehabilitation, and any existing sexual dysfunction should be addressed in the treatment plan. PMID- 27413584 TI - Data Quality Monitoring in Clinical Trials: Has It Been Worth It? An Evaluation and Prediction of the Future by All Stakeholders. AB - This paper summarizes the results of the CNS Summit Data Quality Monitoring Workgroup analysis of current data quality monitoring techniques used in central nervous system (CNS) clinical trials. Based on audience polls conducted at the CNS Summit 2014, the panel determined that current techniques used to monitor data and quality in clinical trials are broad, uncontrolled, and lack independent verification. The majority of those polled endorse the value of monitoring data. Case examples of current data quality methodology are presented and discussed. Perspectives of pharmaceutical companies and trial sites regarding data quality monitoring are presented. Potential future developments in CNS data quality monitoring are described. Increased utilization of biomarkers as objective outcomes and for patient selection is considered to be the most impactful development in data quality monitoring over the next 10 years. Additional future outcome measures and patient selection approaches are discussed. PMID- 27413585 TI - Quetiapine-induced Bradycardia and Hypotension in the Elderly-A Case Report. AB - Quetiapine is increasingly used for the treatment of behavioral and psychological symptoms of dementia in elderly patients. Among the many potential side effects of second-generation antipsychotics, the sudden onset of cardiac abnormality is a particularly important side effect to consider due its fatal implications. Elderly patients may be particularly vulnerable to these cardiac-related side effects due to the likelihood that they have multiple existing health conditions (e.g., heart disease, high blood pressure, diabetes) as well as age-related changes in their pharmacokinetics and pharmacodynamics and differences in their receptor binding profiles. We present a case of an elderly man with a history of heart disease who developed symptomatic bradycardia and hypotension simultaneously while taking quetiapine. After dose reduction and withdrawal of quetiapine, a time sequential improvement of bradycardia and hypotension monitored by repeated electrocardiogram and blood pressure checks suggests a relationship between the higher dosage of quetiapine and cardiac abnormalities. Other factors such as aging itself and chronic heart failure might be associated with cardiac distress. Elderly patients on quetiapine, particularly at higher dosages, should be continually and closely monitored for any symptoms of cardiac distress. PMID- 27413586 TI - Amyotrophic Lateral Sclerosis with Frontotemporal Dementia in the Presence of C9orf72 Repeat Expansion-A Case Report. AB - Amyotrophic lateral sclerosis and frontotemporal dementia are significant neurodegenerative illnesses with possible genetic predispositions. The C9orf72 gene and the GGGGCC repeat expansions of it are reported to have a causative role in the expression of these conditions. We report a case of a patient with autosomal dominant amyotrophic lateral sclerosis and frontotemporal dementia (ALS FTD) in the presence of C9orf72 repeat expansion. We believe our case further supports the theory that the presence of C9orf72 repeat expansion in patients with a family history of amyotrophic lateral sclerosis and/or frontotemporal dementia significantly increases their risk of developing either or both diseases. The development of antisense oligonucleotides that might target GGGGCC RNA sequences theoretically may have a therapeutic role in mitigating the clinical expression of these illnesses. PMID- 27413587 TI - Sleep-isolated Trichotillomania (SITTM): A Case Report. AB - We report a case of sleep-isolated trichotillomania admitted to the hospital for alcohol detoxification. It would be helpful for patients with sleep-isolated trichotillomania to have diagnostic polysomnography to identify any other sleep related pathology and correlate sleep-isolated trichotillomania behaviors with the sleep cycle to identify specific treatment for sleep-isolated trichotillomania. PMID- 27413588 TI - Exploring Mechanisms of Biofilm Removal. AB - OBJECTIVE: The goal of this study was to evaluate the effects of a novel anti plaque formulation on oral biofilm removal. Specific aim was to elucidate the role of 2 potentially complementary mechanisms on dental biofilm removal using EPIEN Dental Debriding Solution (EDDS) like desiccating action leading to denaturation and destabilization of plaque and mechanical removal of destabilized plaque through forceful rinsing action. MATERIALS AND METHODS: 25 extracted teeth, after routine debriding and cleaning, underwent standard biofilm incubation model over 4 days. Then samples were randomly divided into 5 groups of 5 teeth each, treated and stained with GUM(r)Red-Cote(r) plaque disclosing solution and imaged. Samples were subsequently treated with HYBENX(r) Oral Decontaminant. Group 1 samples were treated with a standardized "static" water dip exposure following biofilm incubation. Samples in Group 2 were given a standardized "dynamic" exposure to a dental high pressure air/water syringe for 20 s. Group 3 samples were exposed to a standardized "static" application of test agent (30 s dip rinse) followed by a standardized "static" water rinse (30 s dip rinse). Samples in Group 4 were given both the standardized "static" application of test formulation followed by the standardized "dynamic" exposure to a dental high pressure air/water syringe. Finally, samples in Group 5 were treated with a standardized "dynamic" application of test agent (20 s high pressure syringe at 10 ml/s) followed by the standardized "dynamic" exposure to a dental high pressure air/water syringe. RESULTS: The MPM images demonstrated that the water dip treatment resulted in the persistence of an almost continuous thick layer of biofilm coverage on the tooth surface. Similarly, test agent dip treatment followed by water dip only removed a few patches of biofilm, with the majority of the tooth surface remaining covered by an otherwise continuous layer of biofilm. Samples exposed to air/water spray alone showed some disruption of the biofilm, leaving residual patches of biofilm that varied considerably in size. Test agent dip treatment followed by air/water spray broke up the continuous layer of biofilm leaving only very small, thin scattered islands of biofilm. Finally, the dynamic test agent spray followed by air/water spray removed the biofilm almost entirely, with evidence of only very few small, thin residual biofilm islands. CONCLUSION: These studies demonstrate that test agent desiccant effect alone causes some disruption of dental biofilm. Additional dynamic rinsing is needed to achieve complete removal of dental biofilm. PMID- 27413589 TI - Statistical Assessment of Neighborhood Socioeconomic Deprivation Environment in Spatial Epidemiologic Studies. AB - Neighborhood socioeconomic deprivation has been associated with health behaviors and outcomes. However, neighborhood socioeconomic status has been measured inconsistently across studies. It remains unclear whether appropriate socioeconomic indicators vary over geographic areas and geographic levels. The aim of this study is to compare the composite socioeconomic index to six socioeconomic indicators reflecting different aspects of socioeconomic environment by both geographic areas and levels. Using 2000 U.S. Census data, we performed a multivariate common factor analysis to identify significant socioeconomic resources and constructed 12 composite indexes at the county, the census tract, and the block group levels across the nation and for three states, respectively. We assessed the agreement between composite indexes and single socioeconomic variables. The component of the composite index varied across geographic areas. At a specific geographic region, the component of the composite index was similar at the levels of census tracts and block groups but different from that at the county level. The percentage of population below federal poverty line was a significant contributor to the composite index, regardless of geographic areas and levels. Compared with non-component socioeconomic indicators, component variables were more agreeable to the composite index. Based on these findings, we conclude that a composite index is better as a measure of neighborhood socioeconomic deprivation than a single indicator, and it should be constructed on an area- and unit-specific basis to accurately identify and quantify small-area socioeconomic inequalities over a specific study region. PMID- 27413590 TI - Mass Absorption Coefficient of Tungsten and Tantalum, 1450 eV to 2350 eV: Experiment, Theory, and Application. AB - The mass absorption coefficients of tungsten and tantalum were measured with soft x-ray photons from 1450 eV to 2350 eV using an undulator source. This region includes the M3, M4, and M5 absorption edges. X-ray absorption fine structure was calculated within a real-space multiple scattering formalism; the predicted structure was observed for tungsten and to a lesser degree tantalum as well. Separately, the effects of dynamic screening were observed as shown by an atomic calculation within the relativistic time-dependent local-density approximation. Dynamic screening effects influence the spectra at the 25 % level and are observed for both tungsten and tantalum. We applied these results to characterize spatially-resolved spectra of a tungsten integrated circuit interconnect obtained using a scanning transmission x-ray microscope. The results indicate tungsten fiducial markers were deposited into silica trenches with a depths of 50 % and 60 % of the markers' heights. PMID- 27413591 TI - A Double-Primary Dead-Weight Tester for Pressures (35-175) kPa in Gage Mode. AB - Primary pressure standards in the atmospheric pressure range are often established using mercury manometers. Less frequently, controlled-clearance dead weight testers in which one component (normally the piston) has been dimensionally measured have also been used. Recent advances in technology on two fronts i) the fabrication of large-diameter pistons and cylinders with good geometry; and ii) the ability to measure the dimensions of these components, have allowed some dead-weight testers at NIST to approach total relative uncertainties (k = 2) in dimensionally-derived effective areas near 5 * 10(-6). This paper describes a single piston/cylinder assembly (NIST-PG201WC/WC) that serves as both a primary gage in which both piston and cylinder are measured dimensionally and a controlled-clearance primary gage (employing the Heydemann-Welch method). Thus it allows some previous assumptions about the modeling of dead-weight testers to be checked. For the gage described in this paper the piston/cylinder clearance obtained from the two analyses have relative differences of 4 * 10(-6) to 7 * 10( 6) over the pressure range 35 kPa to 175 kPa. Some implications of these results will be discussed. From the dimensional characterizations and auxiliary measurements we have determined that the effective area for this gauge at 20 degrees C is: [Formula: see text]where P is the system pressure and P J is a control pressure. The estimated relative uncertainty in effective area is 8.2 * 10(-6) +1.4 * 10(-11) P/Pa (k = 2). The temperature coefficient for the area was measured and found to be (9.06 +/- 0.04) * 10(-6)/K. Thus using the gage at a reference temperature of 23 degrees C yields an effective area: [Formula: see text]with almost no increase in the uncertainty over that at 20 degrees C. PMID- 27413592 TI - Design and Uncertainty Analysis for a PVTt Gas Flow Standard. AB - A new pressure, volume, temperature, and, time (PVTt) primary gas flow standard at the National Institute of Standards and Technology has an expanded uncertainty (k = 2) of between 0.02 % and 0.05 %. The standard spans the flow range of 1 L/min to 2000 L/min using two collection tanks and two diverter valve systems. The standard measures flow by collecting gas in a tank of known volume during a measured time interval. We describe the significant and novel features of the standard and analyze its uncertainty. The gas collection tanks have a small diameter and are immersed in a uniform, stable, thermostatted water bath. The collected gas achieves thermal equilibrium rapidly and the uncertainty of the average gas temperature is only 7 mK (22 * 10(-6) T). A novel operating method leads to essentially zero mass change in and very low uncertainty contributions from the inventory volume. Gravimetric and volume expansion techniques were used to determine the tank and the inventory volumes. Gravimetric determinations of collection tank volume made with nitrogen and argon agree with a standard deviation of 16 * 10(-6) VT . The largest source of uncertainty in the flow measurement is drift of the pressure sensor over time, which contributes relative standard uncertainty of 60 * 10(-6) to the determinations of the volumes of the collection tanks and to the flow measurements. Throughout the range 3 L/min to 110 L/min, flows were measured independently using the 34 L and the 677 L collection systems, and the two systems agreed within a relative difference of 150 * 10(-6). Double diversions were used to evaluate the 677 L system over a range of 300 L/min to 1600 L/min, and the relative differences between single and double diversions were less than 75 * 10(-6). PMID- 27413593 TI - Potassium Bromate Assay by Redox Titrimetry Using Arsenic Trioxide. AB - Bromate, a disinfectant, is one of the analytes of interest in wastewater analysis. Environmental laboratories have a regulatory need for their measurements to be traceable to NIST standards. Bromate is not currently certified as a NIST Standard Reference Material (SRM). Therefore, a traceable assay of potassium bromate (KBrO3) is needed. KBrO3 was dissolved in water and assayed by redox titrimetry using arsenic trioxide (As2O3). A nominal (0.1 g) sample of As2O3 was dissolved in 10 mL of 5 mol/L sodium hydroxide. The solution was acidified with hydrochloric acid and about 95 % of the KBrO3 titrant was added gravimetrically. The end point was determined by addition of dilute (1:3) titrant using an automated titrator. The KBrO3 assay was determined to be 99.76 % +/- 0.20 %. The expanded uncertainty considered the titrations of three independently prepared KBrO3 solutions. PMID- 27413594 TI - Optical Diffraction in Close Proximity to Plane Apertures. II. Comparison of Half Plane Diffraction Theories. AB - The accuracy and physical significance of the classical Rayleigh-Sommerfeld and Kirchhoff diffraction integrals are assessed in the context of Sommerfeld's rigorous theory of half-plane diffraction and Maxwell's equations. It is shown that the Rayleigh-Sommerfeld integrals are in satisfactory agreement with Sommerfeld's theory in most of the positive near zone, except at sub-wavelength distances from the screen. On account of the bidirectional nature of diffraction by metallic screens the Rayleigh-Sommerfeld integrals themselves cannot be used for irradiance calculations, but must first be resolved into their forward and reverse components and it is found that Kirchhoff's integral is the appropriate measure of the forward irradiance. Because of the inadequate boundary conditions assumed in their derivation the Rayleigh-Sommerfeld and Kirchhoff integrals do not correctly describe the flow of energy through the aperture. PMID- 27413595 TI - Uncertainties in Interpolated Spectral Data. AB - Interpolation is often used to improve the accuracy of integrals over spectral data convolved with various response functions or power distributions. Formulae are developed for propagation of uncertainties through the interpolation process, specifically for Lagrangian interpolation increasing a regular data set by factors of 5 and 2, and for cubic-spline interpolation. The interpolated data are correlated; these correlations must be considered when combining the interpolated values, as in integration. Examples are given using a common spectral integral in photometry. Correlation coefficients are developed for Lagrangian interpolation where the input data are uncorrelated. It is demonstrated that in practical cases, uncertainties for the integral formed using interpolated data can be reliably estimated using the original data. PMID- 27413596 TI - QUANTITATIVE SYNTHETIC POLYMER MASS SPECTROMETRY WORKSHOP: Gaithersburg, MD November 7-8, 2002. PMID- 27413597 TI - Accuracy of Nanoscale Pitch Standards Fabricated by Laser-Focused Atomic Deposition. AB - The pitch accuracy of a grating formed by laser-focused atomic deposition is evaluated from the point of view of fabricating nanoscale pitch standard artifacts. The average pitch obtained by the process, nominally half the laser wavelength, is simply traceable with small uncertainty to an atomic frequency and hence can be known with very high accuracy. An error budget is presented for a Cr on sapphire sample, showing that a combined standard uncertainty of 0.0049 nm, or a relative uncertainty of 2.3 * 10(-5), is readily obtained, provided the substrate temperature does not change. Precision measurements of the diffraction of the 351.1 nm argon ion laser line from such an artifact are also presented. These yield an average pitch of (212.7777 +/- 0.0069) nm, which agrees well with the expected value, as corrected for thermal contraction, of (212.7705 +/- 0.0049) nm. PMID- 27413598 TI - Characterization of an Ellipsoidal Radiometer. AB - An ellipsoidal radiometer has been characterized using a 25 mm variable temperature blackbody as a radiant source. This radiometer is intended for separating radiation from convection effects in fire test methods. The characterization included angular response, responsivity, and purge-gas flow effect studies. The angular response measurements showed that the reflection from the radiometer cavity was higher on one of the cavity halves relative to the other half. Further development work may be necessary to improve the angular response. The responsivity measured with reference to a transfer-standard electrical-substitution radiometer showed dependence on the distance of the radiometer from the blackbody cavity. The purge-gas had the effect of reducing the signal output nearly linearly with flow rate. PMID- 27413599 TI - Interlaboratory Comparison of Magnetic Thin Film Measurements. AB - A potential low magnetic moment standard reference material (SRM) was studied in an interlaboratory comparison. The mean and the standard deviation of the saturation moment m s, the remanent moment m r, and the intrinsic coercivity H c of nine samples were extracted from hysteresis-loop measurements. Samples were measured by thirteen laboratories using inductive-field loopers, vibrating-sample magnetometers, alternating-gradient force magnetometers, and superconducting quantum-interference-device magnetometers. NiFe films on Si substrates had saturation moment measurements reproduced within 5 % variation among the laboratories. The results show that a good candidate for an SRM must have a highly square hysteresis loop (m r/m s > 90 %), H c ~ 400 A.m(-1) (5 Oe), and m s ~ 2 * 10(-7) A.m(2) (2 * 10(-4) emu). PMID- 27413600 TI - A Primary Dead-Weight Tester for Pressures (0.05-1.0) MPa. AB - Recent advances in technology on two fronts, 1) the fabrication of large-diameter pistons and cylinders with good geometry, and 2) the ability to measure the dimensions of these components with high accuracy, have allowed dead-weight testers at the National Institute of Standards and Technology (NIST) to generate pressures that approach total relative uncertainties previously obtained only by manometers. This paper describes a 35 mm diameter piston/cylinder assembly (known within NIST as PG-39) that serves as a pressure standard in which both the piston and the cylinder have been accurately dimensioned by Physikalisch Technische Bundesanstalt (PTB). Both artifacts (piston and cylinder) appeared to be round within +/-30 nm and straight within +/-100 nm over a substantial fraction of their heights. Based on the diameters at 20 degrees C provided by PTB (+/-15 nm) and on the good geometry of the artifact, the relative uncertainties for the effective area were estimated to be about 2.2 * 10(-6) (1sigma). PMID- 27413601 TI - Thermal Conductivity Measurement of an Electron-Beam Physical-Vapor-Deposition Coating. AB - An industrial ceramic thermal-barrier coating designated PWA 266, processed by electron-beam physical-vapor deposition, was measured using a steady-state thermal conductivity technique. The thermal conductivity of the mass fraction 7 % yttria-stabilized zirconia coating was measured from 100 degrees C to 900 degrees C. Measurements on three thicknesses of coatings, 170 MUm, 350 MUm, and 510 MUm resulted in thermal conductivity in the range from 1.5 W/(m.K) to 1.7 W/(m.K) with a combined relative standard uncertainty of 20 %. The thermal conductivity is not significantly dependent on temperature. PMID- 27413602 TI - Thermal Evaluation of Scorched Graphite-Epoxy Panels by Infrared Scanning. AB - A simple measurement system is described for evaluating damage to graphite-epoxy panels, such as those used in high-performance aircraft. The system uses a heating laser and infrared imaging system to measure thermal performance. Thermal conductivity or diffusivity is a sensitive indicator of damage in materials, allowing this thermal measurement to show various degrees of damage in graphite epoxy composites. Our measurements track well with heat-flux damage to graphite epoxy panels. This measurement system, including analysis software, could easily be used in the field, such as on the deck of an aircraft carrier or at remote air strips. PMID- 27413603 TI - Amorphous Calcium Phosphate-Based Bioactive Polymeric Composites for Mineralized Tissue Regeneration. AB - Amorphous calcium phosphate (ACP), a postulated precursor in the formation of biological hydroxyapatite, has been evaluated as a filler phase in bioactive polymeric composites that utilize dental monomers to form the matrix phase on polymerization. In addition to excellent biocompatibility, these composites provided sustained release of calcium and phosphate ions into simulated saliva milieus. In an effort to enhance the physicochemical and mechanical properties and extend the utility of remineralizing ACP composites to a greater variety of dental applications, we have focused on: a) hybridizing ACP by introducing silica and/or zirconia, b) assessing the efficacy of potential coupling agents, c) investigating the effects of chemical structure and compositional variation of the resin matrices on the mechanical strength and ion-releasing properties of the composites, and d) improving the intrinsic adhesiveness of composites by using bifunctional monomers with an affinity for tooth structure in resin formulations. Si- and Zr-modified ACPs along with several monomer systems are found useful in formulating composites with improved mechanical and remineralizing properties. Structure-property studies have proven helpful in advancing our understanding of the remineralizing behavior of these bioactive composites. It is expected that this knowledge base will direct future research and lead to clinically valuable products, especially therapeutic materials appropriate for the healing or even regeneration of defective teeth and bone structures. PMID- 27413604 TI - An Experimental Method for Measuring Mechanical Properties of Rat Pulmonary Arteries Verified With Latex. AB - This paper describes a test method for measuring the mechanical properties of small, nonlinear membrane samples from a rat model for pulmonary hypertension. The size and nonlinearity of the pulmonary artery samples poses a challenge for developing a test method that will generate quality, reproducible data in the pressure range experienced by the hypertensive pulmonary artery. The experimental method described here has sufficient precision to yield a combined relative standard uncertainty of 4 %. The method is calibrated against 75 um thick latex and the data agree well with the neo-Hookian model. PMID- 27413605 TI - Dependence of Electron Density on Fermi Energy in N-Type Gallium Antimonide. AB - The majority electron density as a function of the Fermi energy is calculated in zinc blende, n-type GaSb for donor densities between 10(16) cm(-3) and 10(19) cm( 3). These calculations solve the charge neutrality equation self-consistently for a four-band model (three conduction sub-bands at Gamma, L, and X and one equivalent valence band at Gamma) of GaSb. Our calculations assume parabolic densities of states and thus do not treat the density-of-states modifications due to high concentrations of dopants, many body effects, and non-parabolicity of the bands. Even with these assumptions, the results are important for interpreting optical measurements such as Raman measurements that are proposed as a nondestructive method for wafer acceptance tests. PMID- 27413606 TI - Radiometric Measurement Comparison on the Integrating Sphere Source Used to Calibrate the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Landsat 7 Enhanced Thematic Mapper Plus (ETM+). AB - As part of a continuing effort to validate the radiometric scales assigned to integrating sphere sources used in the calibration of Earth Observing System (EOS) instruments, a radiometric measurement comparison was held in May 1998 at Raytheon/Santa Barbara Remote Sensing (SBRS). This comparison was conducted in support of the calibration of the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Landsat 7 Enhanced Thematic Mapper Plus (ETM+) instruments. The radiometric scale assigned to the Spherical Integrating Source (SIS100) by SBRS was validated through a comparison with radiometric measurements made by a number of stable, well-characterized transfer radiometers from the National Institute of Standards and Technology (NIST), the National Aeronautics and Space Administration's Goddard Space Flight Center (NASA's GSFC), and the University of Arizona Optical Sciences Center (UA). The measured radiances from the radiometers differed by +/-3 % in the visible to near infrared when compared to the SBRS calibration of the sphere, and the overall agreement was within the combined uncertainties of the individual measurements. In general, the transfer radiometers gave higher values than the SBRS calibration in the near infrared and lower values in the blue. The measurements of the radiometers differed by +/-4 % from 800 nm to 1800 nm compared to the SBRS calibration of the sphere, and the overall agreement was within the combined uncertainties of the individual measurements for wavelengths less than 2200 nm. The results of the radiometric measurement comparison presented here supplement the results of previous measurement comparisons on the integrating sphere sources used to calibrate the Multi-angle Imaging SpectroRadiometer (MISR) at NASA's Jet Propulsion Laboratory (JPL), Pasadena, CA and the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) at NEC Corporation, Yokohama, Japan. PMID- 27413607 TI - Relating Fresh Concrete Viscosity Measurements from Different Rheometers. AB - Concrete rheological properties need to be properly measured and predicted in order to characterize the workability of fresh concrete, including special concretes such as self-consolidating concrete (SCC). It was shown by a round robin test held in 2000 [1,2] that different rheometer designs gave different values of viscosity for the same concrete. While empirical correlation between different rheometers was possible, for a procedure that is supposed to "scientifically" improve on the empirical slump tests, this situation is unsatisfactory. To remedy this situation, a new interpretation of the data was developed. In this paper, it is shown that all instruments tested could be directly and quantitatively compared in terms of relative plastic viscosity instead of the plastic viscosity alone. This should eventually allow the measurements from various rheometer designs to be directly calibrated against known standards of plastic viscosity, putting concrete rheometry and concrete workability on a sounder materials science basis. PMID- 27413608 TI - Repeatability and Reproducibility Standard Deviations in the Measurement of Trace Moisture Generated Using Permeation Tubes. AB - Permeation-tube moisture generators are used in industry as calibrated sources of water vapor and carrier gas mixtures. Measurements were made using three permeation-tube moisture generators of the type used in the semiconductor industry. This paper describes repeatability and reproducibility standard deviations in measurement of moisture concentration from such generators. Repeatability refers to measurements within a system and reproducibility refers to measurements between systems. Two independent methods were used to measure the realized concentration of water vapor. The first measurement, the calculated value, was determined using calibrated permeation rate of permeation-tube and flow rate of dry carrier gas. This is the industrial method of evaluating moisture concentration. The second measurement, the measured value, was determined using the low frost-point generator at the National Institute of Standards and Technology (NIST) and a quartz-crystal-micro-balance. Four pairs of independent measurements for each generator and for six nominal levels in the range from10 nL/L to 100 nL/L were made. The characteristic used to quantify repeatability and reproducibility standard deviations in industrial measurements is the calculated value minus the measured value. Repeatability standard deviation ranges from 1 nL/L to 2 nL/L, approximately. Reproducibility standard deviation ranges from 2 nL/L to 8 nL/L, approximately. The documentary ASTM standard E691-99 was used for both data validation and quantification of the repeatability and reproducibility standard deviations. PMID- 27413609 TI - Review of Instrumented Indentation. AB - Instrumented indentation, also known as depth-sensing indentation or nanoindentation, is increasingly being used to probe the mechanical response of materials from metals and ceramics to polymeric and biological materials. The additional levels of control, sensitivity, and data acquisition offered by instrumented indentation systems have resulted in numerous advances in materials science, particularly regarding fundamental mechanisms of mechanical behavior at micrometer and even sub-micrometer length scales. Continued improvements of instrumented indentation testing towards absolute quantification of a wide range of material properties and behavior will require advances in instrument calibration, measurement protocols, and analysis tools and techniques. In this paper, an overview of instrumented indentation is given with regard to current instrument technology and analysis methods. Research efforts at the National Institute of Standards and Technology (NIST) aimed at improving the related measurement science are discussed. PMID- 27413610 TI - Towards High Accuracy Reflectometry for Extreme-Ultraviolet Lithography. AB - Currently the most demanding application of extreme ultraviolet optics is connected with the development of extreme ultraviolet lithography. Not only does each of the Mo/Si multilayer extreme-ultraviolet stepper mirrors require the highest attainable reflectivity at 13 nm (nearly 70 %), but the central wavelength of the reflectivity of these mirrors must be measured with a wavelength repeatability of 0.001 nm and the peak reflectivity of the reflective masks with a repeatability of 0.12 %. We report on two upgrades of our NIST/DARPA Reflectometry Facility that have given us the ability to achieve 0.1 % repeatability and 0.3 % absolute uncertainty in our reflectivity measurements. A third upgrade, a monochromator with thermal and mechanical stability for improved wavelength repeatability, is currently in the design phase. PMID- 27413612 TI - On the Stability of Exponential Backoff. AB - Random access schemes for packet networks featuring distributed control require algorithms and protocols for resolving packet collisions that occur as the uncoordinated terminals contend for the channel. A widely used collision resolution protocol is the exponential backoff (EB). New analytical results for the stability of the (binary) EB are given. Previous studies on the stability of the (binary) EB have produced contradictory results instead of a consensus: some proved instability, others showed stability under certain conditions. In these studies, simplified and/or modified models of the backoff algorithm were used. In this paper, care is taken to use a model that reflects the actual behavior of backoff algorithms. We show that EB is stable under a throughput definition of stability; the throughput of the network converges to a non-zero constant as the offered load N goes to infinity. We also obtain the analytical expressions for the saturation throughput for a given number of nodes, N. The analysis considers the general case of EB with backoff factor r, where BEB is the special case with r = 2. We show that r = 1/(1 - e(-1)) is the optimum backoff factor that maximizes the throughput. The accuracy of the analysis is checked against simulation results. PMID- 27413611 TI - Virtual Environment for Manipulating Microscopic Particles With Optical Tweezers. AB - In this paper, virtual reality techniques are used to define an intuitive interface to a nanoscale manipulation device. This device utilizes optical methods to focus laser light to trap and reposition nano-to-microscopic particles. The underlying physics are simulated by the use of Lagrange mechanics. A unique control method for the manipulation of the particles is also provided. The user can naturally grab and steer the particles. Behind the scene, a complex computation is performed to find the new location of the potential field induced by the laser beam that would move the particles accordingly. Haptic feedback is used to constrain the steering motion within the physical capability of the potential field. PMID- 27413613 TI - A Link-Level Simulator of the cdma2000 Reverse-Link Physical Layer. AB - The cdma2000 system is an evolutionary enhancement of the IS-95 standards which support 3G services defined by the International Telecommunications Union (ITU). cdma2000 comes in two phases: 1XRTT and 3XRTT (1X and 3X indicates the number of 1.25 MHz wide radio carrier channels used and RTT stands for Radio Transmission Technology). The cdma2000 1XRTT, which operates within a 1.25 MHz bandwidth, can be utilized in existing IS-95 CDMA channels as it uses the same bandwidth, while 3XRTT requires the commitment of 5 MHz bandwidth to support higher data rates. This paper describes a software model implementation of the cdma2000 reverse link and its application for evaluating the effect of rake receiver design parameters on the system performance under various multipath fading conditions. The cdma2000 models were developed at the National Institute of Standards and Technology (NIST), using SPW (Signal Processing Worksystem) commercial software tools. The model has been developed in a generic manner that includes all the reverse link six radio configurations and their corresponding data rates, according to cdma2000 specifications. After briefly reviewing the traffic channel characteristics of the cdma2000 reverse link (subscriber to base station), the paper discusses the rake receiver implementation including an ideal rake receiver. It then evaluates the performance of each receiver for a Spreading Rate 3 (3XRTT) operation, which is considered as a true "3G" cdma2000 technology. These evaluations are based on the vehicular IMT-2000 (International Mobile Telecommunication 2000) channel model using the link budget defined in cdma2000 specifications for the reverse link. PMID- 27413614 TI - New National Air-Kerma-Strength Standards for (125)I and (103)Pd Brachytherapy Seeds. AB - The new U.S. measurement standard for the air-kerma strength from low-energy photon-emitting brachytherapy seed sources is formally described in detail. This instrument-based standard was implemented on 1 January 1999, with its salient features and the implications of differences with the previous standard given only through a series of informal communications. The Wide-Angle Free-Air Chamber (WAFAC) is specially designed to realize air kerma from a single-seed source emitting photons with energies up to about 40 keV, and is now used to measure the wide variety of seeds used in prostate-cancer therapy that has appeared in the last few years. For the two (125)I seed models that have been subject to both the old and new standards, the new standard reduces the air-kerma strength by 10.3 %. This change is mainly due to the removal of the influence on the measurement of the Ti K x rays produced in the source encapsulation, a component with no clinical significance. PMID- 27413615 TI - Changes in the U.S. Primary Standards for the Air Kerma From Gamma-Ray Beams. AB - Monte Carlo photon-electron transport calculations have been done to derive new wall corrections for the six NBS-NIST standard graphite-wall, air-ionization cavity chambers that serve as the U.S. national primary standard for air kerma (and exposure) for gamma rays from (60)Co, (137)Cs, and (192)Ir sources. The data developed for and from these calculations have also been used to refine a number of other factors affecting the standards. The largest changes are due to the new wall corrections, and the total changes are +0.87 % to +1.11 % (depending on the chamber) for (60)Co beams, +0.64 % to +1.07 % (depending on the chamber) for (137)Cs beams, and -0.06 % for the single chamber used in the measurement of the standardized (192)Ir source. The primary standards for air kerma will be adjusted in the near future to reflect the changes in factors described in this work. PMID- 27413616 TI - Comparison of the NIST and BIPM Medium-Energy X-Ray Air-Kerma Measurements. AB - The air-kerma standards used for the measurement of medium-energy x rays were compared at the National Institute of Standards and Technology (NIST) and at the Bureau International des Poids et Mesures (BIPM). The comparison involved a series of measurements at the BIPM and the NIST using the air-kerma standards and two NIST reference-class transfer ionization standards. Reference beam qualities in the range from 60 kV to 300 kV were used. The results show the standards to be in agreement within the combined standard uncertainty of the comparison of 0.35 %. PMID- 27413618 TI - A Logical Model of Conceptual Integrity in Data Integration. AB - Conceptual integrity is required for the result of data integration to be cohesive and sensible. Compromised conceptual integrity results in "semantic faults," which are commonly blamed for latent integration bugs. A logical model of conceptual integrity in data integration and a simple example application are presented. Unlike constructive models that attempt to prevent semantic faults, this model allows both correct and incorrect integrations to be described. Imperfect legacy systems can therefore be modeled, allowing a more formal analysis of their flaws and the possible remedies. PMID- 27413617 TI - Optical-Fiber Power Meter Comparison Between NIST and PTB. AB - We describe the results of a comparison of reference standards between the National Institute of Standards and Technology (NIST-USA) and Physikalisch Technische Bundesanstalt (PTB-Germany) at nominal wavelengths of 1300 nm and 1550 nm using an optical-fiber cable. Both laboratories used thermal detectors as reference standards. A novel temperature-controlled, optical-trap detector was used as a transfer standard to compare two reference standards. Measurement results showed differences of less than 1.5 * 10(-3), which is within the combined uncertainty for both laboratories. PMID- 27413619 TI - Simulation of an Austenite-Twinned-Martensite Interface. AB - Developing numerical methods for predicting microstructure in materials is a large and important research area. Two examples of material microstructures are Austenite and Martensite. Austenite is a microscopic phase with simple crystallographic structure while Martensite is one with a more complex structure. One important task in materials science is the development of numerical procedures which accurately predict microstructures in Martensite. In this paper we present a method for simulating material microstructure close to an Austenite Martensite interface. The method combines a quasi-Newton optimization algorithm and a nonconforming finite element scheme that successfully minimizes an approximation to the total stored energy near the interface of interest. Preliminary results suggest that the minimizers of this energy functional located by the developed numerical algorithm appear to display the desired characteristics. PMID- 27413620 TI - High Accuracy Ultraviolet Index of Refraction Measurements Using a Fourier Transform Spectrometer. AB - We have constructed a new facility at the National Institute of Standards and Technology (NIST) to measure the index of refraction of transmissive materials in the wavelength range from the visible to the vacuum ultraviolet. An etalon of the material is illuminated with synchrotron radiation, and the interference fringes in the transmittance spectrum are measured using a Fourier transform spectrometer. The refractive index of calcium fluoride, CaF2, has been measured from 600 nm to 175 nm and the resulting values agree with a traditional goniometric measurement to within 1 * 10(-5). The uncertainty in the index values is currently limited by the uncertainty in the thickness measurement of the etalon. PMID- 27413621 TI - Statistical Interpretation of Key Comparison Reference Value and Degrees of Equivalence. AB - Key comparisons carried out by the Consultative Committees (CCs) of the International Committee of Weights and Measures (CIPM) or the Bureau International des Poids et Mesures (BIPM) are referred to as CIPM key comparisons. The outputs of a statistical analysis of the data from a CIPM key comparison are the key comparison reference value, the degrees of equivalence, and their associated uncertainties. The BIPM publications do not discuss statistical interpretation of these outputs. We discuss their interpretation under the following three statistical models: nonexistent laboratory-effects model, random laboratory-effects model, and systematic laboratory-effects model. PMID- 27413622 TI - The Normalized Reduced Form and Cell Mathematical Tools for Lattice Analysis Symmetry and Similarity. AB - To intelligently and effectively use crystallographic databases, mathematical and computer tools are required that can elucidate diverse types of intra- and interlattice relationships. Two such tools are the normalized reduced form and normalized reduced cell. Practical experience has revealed that the first tool the normalized reduced form-is very helpful in establishing lattice metric symmetry as it enables one to readily deduce significant relationships between the elements of the reduced form. Likewise research with crystallographic databases has demonstrated that the second tool-the normalized reduced cell-plays a vital role in determining metrically similar lattices. Knowledge of similar lattices has practical value in solving structures, in assignment of structure types, in materials design, and in nano-technology. In addition to using the reduced cell, it is recommended that lattice-matching strategies based on the normalized reduced cell be routinely carried out in database searching, in data evaluation, and in experimental work. PMID- 27413623 TI - Evaluation of Intrusion Detection Systems. AB - This paper presents a comprehensive method for evaluating intrusion detection systems (IDSs). It integrates and extends ROC (receiver operating characteristic) and cost analysis methods to provide an expected cost metric. Results are given for determining the optimal operation of an IDS based on this expected cost metric. Results are given for the operation of a single IDS and for a combination of two IDSs. The method is illustrated for: 1) determining the best operating point for a single and double IDS based on the costs of mistakes and the hostility of the operating environment as represented in the prior probability of intrusion and 2) evaluating single and double IDSs on the basis of expected cost. A method is also described for representing a compound IDS as an equivalent single IDS. Results are presented from the point of view of a system administrator, but they apply equally to designers of IDSs. PMID- 27413624 TI - Cryorecovery of Mouse Sperm by Different IVF Methods Using MBCD and GSH. AB - Different protocols incorporating methyl-beta-cyclodextrin (MBCD) and reduced glutathione (GSH) have been reported to improve IVF recovery of cryopreserved mouse sperm on a C57BL/6 (J and N) genetic background. However, it is not clear which IVF protocol is most appropriate when using the various methods to cryorecover sperm with different sperm quality and sample volumes. Therefore, in the present study we correlated sperm motility with fertilization rate and compared the efficiency of different IVF methods using various sperm samples so as to establish general guidelines for mouse sperm cryorecovery by IVF. High linear correlation between sperm fertilization rate and progressive motility was found, R2 was 0.9623 and 0.9993 for pre-freezing and post-thaw progressive motility, respectively. High amounts of cryoprotective agent (CPA) were observed to impair both sperm capacitation and fertilization. Moreover, the presence of a large number of immotile sperm in the sperm-oocyte co-incubation drop was found to reduce IVF success which could be partially reversed by supplementation using monothioglycerol (MTG) during centrifugation. It was concluded that the efficiency of IVF using cryorecovered mouse sperm in media containing MBCD and GSH can be predicted from sperm progressive motility. High concentrations of CPA and immotile sperm should be mitigated prior to IVF. The optimum IVF method should be selected based on sperm sample volume and sperm parameters. PMID- 27413625 TI - Racial Disparities in the Prevalence of Arthritis among Native Hawaiians and Pacific Islanders, Whites, and Asians. AB - The health disparities of Native Hawaiians and Pacific Islanders (NHPI) are well established for diabetes and cardiovascular disease, but less is known about disparities in arthritis. This study examined possible disparities in the prevalence of arthritis by age, sex, and severity comparing NHPI, Whites, and Asians. The study population included adult Hawai'i participants in the 2013 Behavioral Risk Factor Surveillance Survey. NHPI males had a significantly higher prevalence of arthritis, which peaked twenty years earlier, than White and Asian males (P<.001). The prevalence of arthritis peaked at 65-79 years in males and females in all racial groups, except in NHPI males where it peaked at 45-54 years. The mean ages (years) for males with arthritis were 46.2 for NHPI, 59.1 for Whites, and 60.5 for Asians; the respective ages for females were 54.2, 60.5, and 58.8. NHPI males body mass index averaged 2.4 kg/m(2) greater than White males (P<.001), and obese NHPI males had twice the age-adjusted odds of arthritis than obese White males. Although NHPI females had a greater body mass index than White females (P=.05), the prevalence of arthritis was only slightly and not significantly higher. NHPI males and females reported high pain scores more frequently than Whites did, but the differences did not reach statistical significance. Diabetes was a comorbidity more than twice as often in NHPI and Asians of both sexes than among Whites. This study demonstrated racial disparities in the prevalence of arthritis among NHPI, Whites, and Asians. PMID- 27413626 TI - Modifiable Determinants of Obesity in Native Hawaiian and Pacific Islander Youth. AB - In the United States, obesity continues to be a major public health concern. Obesity disproportionately affects Native Hawaiian and Other Pacific Islanders (NHOPI) who demonstrate alarming rates of obesity and its related chronic conditions. However, little is known about the causes of obesity for this group. Given the modest effects of individual-level obesity treatments, identifying the most impactful determinants that can be modified to prevent or reduce obesity in NHOPI youth is critical to the development of interventions that best meet the needs of this population. A systematic review was conducted in PubMed, with additional expert-recommended articles identified through the Hawai'i Initiative for Childhood Obesity Research and Education (HICORE) research database, to evaluate the current body of research on modifiable determinants or correlates of obesity in NHOPI youth. Of an initial pool of 471 articles, 60 articles were read in full and 14 articles were selected for inclusion in the qualitative synthesis. Utilizing an ecological framework to identify gaps in the literature and suggest areas for future research, findings from this review indicate that early life and contextual factors-namely, infant-feeding mode, geographic location, and education-appear to play an important role in obesity in NHOPI youth. However, more research is needed, particularly pre-birth cohort studies evaluating the effects of prenatal and early life risk factors, studies on the sociocultural influences on obesity-related psychosocial factors and health behaviors, as well as the influence of environmental and policy-level variables. PMID- 27413627 TI - Sudden Sensorineural Hearing Loss: Primary Care Update. AB - The primary care physician's role in recognizing sudden sensorineural hearing (SSNHL) loss and delivering initial treatment is critical in the management of the syndrome. This role involves recognizing its clinical symptoms, distinguishing it from conductive hearing loss with the Weber tuning fork or the Rauch hum test, and urgent administration of high dose oral corticosteroids. Diagnosis and treatment should not be delayed for audiometric testing or referral to otolaryngology. This paper provides an update on the initial evaluation and treatment of this syndrome based on the literature and clinical guideline recommendations. PMID- 27413628 TI - Medical School Hotline: "Leading Change" Speech Delivered at the JABSOM Convocation, May 15, 2016 Kennedy Theater, University of Hawai'i, Honolulu, HI. PMID- 27413629 TI - Insights in Public Health: Initial Systematic Reviews of the Deaths of Clients in the State of Hawai'i Developmental Disabilities System. PMID- 27413632 TI - A new method for ecoacoustics? Toward the extraction and evaluation of ecologically-meaningful soundscape components using sparse coding methods. AB - Passive acoustic monitoring is emerging as a promising non-invasive proxy for ecological complexity with potential as a tool for remote assessment and monitoring (Sueur & Farina, 2015). Rather than attempting to recognise species specific calls, either manually or automatically, there is a growing interest in evaluating the global acoustic environment. Positioned within the conceptual framework of ecoacoustics, a growing number of indices have been proposed which aim to capture community-level dynamics by (e.g., Pieretti, Farina & Morri, 2011; Farina, 2014; Sueur et al., 2008b) by providing statistical summaries of the frequency or time domain signal. Although promising, the ecological relevance and efficacy as a monitoring tool of these indices is still unclear. In this paper we suggest that by virtue of operating in the time or frequency domain, existing indices are limited in their ability to access key structural information in the spectro-temporal domain. Alternative methods in which time-frequency dynamics are preserved are considered. Sparse-coding and source separation algorithms (specifically, shift-invariant probabilistic latent component analysis in 2D) are proposed as a means to access and summarise time-frequency dynamics which may be more ecologically-meaningful. PMID- 27413631 TI - The mechanisms of HSC activation and epigenetic regulation of HSCs phenotypes. AB - Epigenetics is a dynamically expanding field of science entailing numerous regulatory mechanisms controlling changes of gene expression in response to environmental factors. Over the recent years there has been a great interest in epigenetic marks as a potential diagnostic and prognostic tool or future target for treatment of various human diseases. There is an increasing body of published research to suggest that epigenetic events regulate progression of chronic liver disease. Experimental manipulation of epigenetic signatures such as DNA methylation, histone acetylation / methylation and the activities of proteins that either annotate or interpret these epigenetic marks can have profound effects on the activation and phenotype of HSC, key cells responsible for onset and progression of liver fibrosis. This review presents recent advances in epigenetic alterations, which could provide mechanistic insight into the pathogenesis of chronic liver disease and provide novel clinical applications. PMID- 27413633 TI - The crouching of the shrew: Mechanical consequences of limb posture in small mammals. AB - An important trend in the early evolution of mammals was the shift from a sprawling stance, whereby the legs are held in a more abducted position, to a parasagittal one, in which the legs extend more downward. After that transition, many mammals shifted from a crouching stance to a more upright one. It is hypothesized that one consequence of these transitions was a decrease in the total mechanical power required for locomotion, because side-to-side accelerations of the body have become smaller, and thus less costly with changes in limb orientation. To test this hypothesis we compared the kinetics of locomotion in two mammals of body size close to those of early mammals (< 40 g), both with parasagittally oriented limbs: a crouching shrew (Blarina brevicauda; 5 animals, 17 trials) and a more upright vole (Microtus pennsylvanicus; 4 animals, 22 trials). As predicted, voles used less mechanical power per unit body mass to perform steady locomotion than shrews did (P = 0.03). However, while lateral forces were indeed smaller in voles (15.6 +/- 2.0% body weight) than in shrews (26.4 +/- 10.9%; P = 0.046), the power used to move the body from side-to-side was negligible, making up less than 5% of total power in both shrews and voles. The most power consumed for both species was that used to accelerate the body in the direction of travel, and this was much larger for shrews than for voles (P = 0.01). We conclude that side-to-side accelerations are negligible for small mammals-whether crouching or more upright-compared to their sprawling ancestors, and that a more upright posture further decreases the cost of locomotion compared to crouching by helping to maintain the body's momentum in the direction of travel. PMID- 27413634 TI - Sub-chronic testosterone treatment increases the levels of epithelial sodium channel (ENaC)-alpha, beta and gamma in the kidney of orchidectomized adult male Sprague-Dawley rats. AB - Testosterone has been reported to cause blood pressure to increase. However mechanisms that underlie the effect of this hormone on this physiological parameter are currently not well understood. The aims of this study were to investigate effects of testosterone on expression of alpha, beta and gamma epithelial sodium channel (ENaC) proteins and messenger RNAs (mRNAs) in kidneys, the channel known to be involved in Na(+) reabsorption, which subsequently can affect the blood pressure. Methods. Adult male Sprague-Dawley (SD) rats were orchidectomized fourteen days prior to receiving seven days treatment with testosterone propionate (125 ug/kg/day or 250 ug/kg/day) with or without flutamide (androgen receptor blocker) or finasteride (5alpha-reductase inhibitor). Following sacrifice, the kidneys were removed and were subjected for alpha, beta and gamma-ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR) respectively. The distribution of alpha, beta and gamma-ENaC proteins in kidneys were observed by immunofluorescence. Results. The alpha, beta and gamma-ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. In these rats, alpha, beta and gamma-ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. Co-treatment with flutamide or finasteride resulted in the levels of alpha, beta and gamma-ENaC proteins and mRNAs in kidneys to decrease. In conclusions, increases in alpha, beta and gamma-ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na(+) reabsorption which subsequently might cause an increase in blood pressure. PMID- 27413635 TI - Pteridine levels and head weights are correlated with age and colony task in the honey bee, Apis mellifera. AB - Background. The age of an insect strongly influences many aspects of behavior and reproduction. The interaction of age and behavior is epitomized in the temporal polyethism of honey bees in which young adult bees perform nurse and maintenance duties within the colony, while older bees forage for nectar and pollen. Task transition is dynamic and driven by colony needs. However, an abundance of precocious foragers or overage nurses may have detrimental effects on the colony. Additionally, honey bee age affects insecticide sensitivity. Therefore, determining the age of a set of individual honey bees would be an important measurement of colony health. Pteridines are purine-based pigment molecules found in many insect body parts. Pteridine levels correlate well with age, and wild caught insects may be accurately aged by measuring pteridine levels. The relationship between pteridines and age varies with a number of internal and external factors among many species. Thus far, no studies have investigated the relationship of pteridines with age in honey bees. Methods. We established single cohort colonies to obtain age-matched nurse and forager bees. Bees of known ages were also sampled from colonies with normal demographics. Nurses and foragers were collected every 3-5 days for up to 42 days. Heads were removed and weighed before pteridines were purified and analyzed using previously established fluorometric methods. Results. Our analysis showed that pteridine levels significantly increased with age in a linear manner in both single cohort colonies and colonies with normal demography. Pteridine levels were higher in foragers than nurses of the same age in bees from single cohort colonies. Head weight significantly increased with age until approximately 28-days of age and then declined for both nurse and forager bees in single cohort colonies. A similar pattern of head weight in bees from colonies with normal demography was observed but head weight was highest in 8-day old nurse bees and there was no relationship of head weight with age of foragers. Discussion. Although the relationship between pteridine levels and age was significant, variation in the data yielded a +4-day range in age estimation. This allows an unambiguous method to determine whether a bee may be a young nurse or old forager in colonies with altered demographics as in the case of single cohort colonies. Pteridine levels in bees do not correlate with age as well as in other insects. However, most studies used insects reared under tightly controlled laboratory conditions, while we used free-living bees. The dynamics of head weight change with age is likely to be due to growth and atrophy of the hypopharyngeal glands. Taken together, these methods represent a useful tool for assessing the age of an insect. Future studies utilizing these methods will provide a more holistic view of colony health. PMID- 27413636 TI - Virus wars: using one virus to block the spread of another. AB - The failure of traditional interventions to block and cure HIV infections has led to novel proposals that involve treating infections with therapeutic viruses infectious viruses that specifically inhibit HIV propagation in the host. Early efforts in evaluating these proposals have been limited chiefly to mathematical models of dynamics, for lack of suitable empirical systems. Here we propose, develop and analyze an empirical system of a therapeutic virus that protects a host cell population against a lethal virus. The empirical system uses E. coli bacteria as the host cell population, an RNA phage as the lethal virus and a filamentous phage as the therapeutic virus. Basic dynamic properties are established for each virus alone and then together. Observed dynamics broadly agree with those predicted by a computer simulation model, although some differences are noted. Two cases of dynamics are contrasted, differing in whether the therapeutic virus is introduced before the lethal virus or after the lethal virus. The therapeutic virus increases in both cases but by different mechanisms. With the therapeutic virus introduced first, it spreads infectiously without any appreciable change in host dynamics. With the therapeutic virus introduced second, host abundance is depressed at the time therapy is applied; following an initial period of therapeutic virus spread by infection, the subsequent rise of protection is through reproduction by hosts already protected. This latter outcome is due to inheritance of the therapeutic virus state when the protected cell divides. Overall, the work establishes the feasibility and robustness to details of a viral interference using a therapeutic virus. PMID- 27413637 TI - The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells. AB - Background. Glufosfamide (GLU) is a glucose conjugate of ifosfamide in which isophosphoramide mustard is glycosidically linked to the beta-D-glucose molecule. Based on GLU structure, it is considered a targeted chemotherapy with fewer side effects. The main objective of the current study is to assess the cytotoxic potential of GLU for the first time in prostate cancer (PC) cells representing different stages of the tumor. Furthermore, this study examined the potential synergistic activity of GLU in combination with docetaxel (DOC). Methods. Two different cell lines were used, LNCaP and PC-3. Concentration-response curves were assessed. The tested groups per cell line were, control, GLU, DOC and combination. Treatment duration was 72 h. Cytotoxicity was assessed using sulforhodamine B (SRB) assay and half maximal inhibitory concentration (IC50) was calculated. Synergy analyses were performed using Calcusyn((r))software. Subsequent mechanistic studies included beta-glucosidase activity assay, glucose uptake and apoptosis studies, namely annexin V-FITC assay and the protein expression of mitochondrial pathway signals including Bcl-2, Bax, Caspase 9 and 3 were assessed. Data are presented as mean +/- SD; comparisons were carried out using one way analysis of variance (ANOVA) followed by Tukey-Kramer's test for post hoc analysis. Results. GLU induced cytotoxicity in both cell lines in a concentration-dependent manner. The IC50 in PC-3 cells was significantly lower by 19% when compared to that of LNCaP cells. The IC50 of combining both drugs showed comparable effect to DOC in PC-3 but was tremendously lowered by 49% compared to the same group in LNCaP cell line. beta-glucosidase activity was higher in LNCaP by about 67% compared to that determined in PC-3 cells while the glucose uptake in PC-3 cells was almost 2 folds that found in LNCaP cells. These results were directly correlated to the efficacy of GLU in each cell line. Treatment of PC cells with GLU as single agent or in combination with DOC induced significantly higher apoptosis as evidenced by Annexin V-staining. Apoptosis was significantly increased in combination group by 4.9 folds and by 2.1 Folds when compared to control in LNCaP cells and PC-3 cells; respectively. Similarly, the expression of Bcl-2 was significantly decreased while Bax, caspase 9 and 3 were significantly increased in the combined treatment groups compared to the control. Conclusion. GLU has a synergistic effect in combination with DOC as it increases the cell kill which can be attributed at least partially to apoptosis in both the tested cell lines and it is suggested as a new combination regimen to be considered in the treatment of the prostate cancer. Further experiments and clinical investigations are needed for assessment of that regimen. PMID- 27413639 TI - Cost-benefit trade-offs of bird activity in apple orchards. AB - Birds active in apple orchards in south-eastern Australia can contribute positively (e.g., control crop pests) or negatively (e.g., crop damage) to crop yields. Our study is the first to identify net outcomes of these activities, using six apple orchards, varying in management intensity, in south-eastern Australia as a study system. We also conducted a predation experiment using real and artificial codling moth (Cydia pomonella) larvae (a major pest in apple crops). We found that: (1) excluding birds from branches of apple trees resulted in an average of 12.8% more apples damaged by insects; (2) bird damage to apples was low (1.9% of apples); and (3) when trading off the potential benefits (biological control) with costs (bird damage to apples), birds provided an overall net benefit to orchard growers. We found that predation of real codling moth larvae was higher than for plasticine larvae, suggesting that plasticine prey models are not useful for inferring actual predation levels. Our study shows how complex ecological interactions between birds and invertebrates affect crop yield in apples, and provides practical strategies for improving the sustainability of orchard systems. PMID- 27413638 TI - Emergent properties of a computational model of tumour growth. AB - While there have been enormous advances in our understanding of the genetic drivers and molecular pathways involved in cancer in recent decades, there also remain key areas of dispute with respect to fundamental theories of cancer. The accumulation of vast new datasets from genomics and other fields, in addition to detailed descriptions of molecular pathways, cloud the issues and lead to ever greater complexity. One strategy in dealing with such complexity is to develop models to replicate salient features of the system and therefore to generate hypotheses which reflect on the real system. A simple tumour growth model is outlined which displays emergent behaviours that correspond to a number of clinically relevant phenomena including tumour growth, intra-tumour heterogeneity, growth arrest and accelerated repopulation following cytotoxic insult. Analysis of model data suggests that the processes of cell competition and apoptosis are key drivers of these emergent behaviours. Questions are raised as to the role of cell competition and cell death in physical cancer growth and the relevance that these have to cancer research in general is discussed. PMID- 27413640 TI - An exploration of the influence of diagonal dissociation and moderate changes in speed on locomotor parameters in trotting horses. AB - Background. Although the trot is described as a diagonal gait, contacts of the diagonal pairs of hooves are not usually perfectly synchronized. Although subtle, the timing dissociation between contacts of each diagonal pair could have consequences on gait dynamics and provide insight into the functional strategies employed. This study explores the mechanical effects of different diagonal dissociation patterns when speed was matched between individuals and how these effects link to moderate, natural changes in trotting speed. We anticipate that hind-first diagonal dissociation at contact increases with speed, diagonal dissociation at contact can reduce collision-based energy losses and predominant dissociation patterns will be evident within individuals. Methods. The study was performed in two parts: in the first 17 horses performed speed-matched trotting trials and in the second, five horses each performed 10 trotting trials that represented a range of individually preferred speeds. Standard motion capture provided kinematic data that were synchronized with ground reaction force (GRF) data from a series of force plates. The data were analyzed further to determine temporal, speed, GRF, postural, mass distribution, moment, and collision dynamics parameters. Results. Fore-first, synchronous, and hind-first dissociations were found in horses trotting at (3.3 m/s +/- 10%). In these speed-matched trials, mean centre of pressure (COP) cranio-caudal location differed significantly between the three dissociation categories. The COP moved systematically and significantly (P = .001) from being more caudally located in hind-first dissociation (mean location = 0.41 +/- 0.04) through synchronous (0.36 +/- 0.02) to a more cranial location in fore-first dissociation (0.32 +/- 0.02). Dissociation patterns were found to influence function, posture, and balance parameters. Over a moderate speed range, peak vertical forelimb GRF had a strong relationship with dissociation time (R = .594; P < .01) and speed (R = .789; P < .01), but peak vertical hindlimb GRF did not have a significant relationship with dissociation time (R = .085; P > 0.05) or speed (R = .223; P = .023). Discussion. The results indicate that at moderate speeds individual horses use dissociation patterns that allow them to maintain trunk pitch stability through management of the cranio-caudal location of the COP. During the hoof-ground collisions, reduced mechanical energy losses were found in hind-first dissociations compared to fully synchronous contacts. As speed increased, only forelimb vertical peak force increased so dissociations tended towards hind-first, which shifted the net COP caudally and balanced trunk pitching moments. PMID- 27413641 TI - Protogyny in a tropical damselfish: females queue for future benefit. AB - Membership of the group is a balance between the benefits associated with group living and the cost of socially constrained growth and breeding opportunities, but the costs and benefits are seldom examined. The goal of the present study was to explore the trade-offs associated with group living for a sex-changing, potentially protogynous coral reef fish, the Ambon damselfish, Pomacentrus amboinensis. Extensive sampling showed that the species exhibits resource defence polygyny, where dominant males guard a nest site that is visited by females. P. amboinensis have a longevity of about 6.5 years on the northern Great Barrier Reef. While the species can change sex consistent with being a protogynous hermaphrodite, it is unclear the extent to which the species uses this capability. Social groups are comprised of one reproductive male, 1-7 females and a number of juveniles. Females live in a linear dominance hierarchy, with the male being more aggressive to the beta-female than the alpha-female, who exhibits lower levels of ovarian cortisol. Surveys and a tagging study indicated that groups were stable for at least three months. A passive integrated transponder tag study showed that males spawn with females from their own group, but also females from neighbouring groups. In situ behavioural observations found that alpha-females have priority of access to the nest site that the male guarded, and access to higher quality foraging areas. Male removal studies suggest that the alpha-females can change sex to take over from the male when the position becomes available. Examination of otolith microstructure showed that those individuals which change sex to males have different embryonic characteristics at hatching, suggesting that success may involve a component that is parentally endowed. The relative importance of parental effects and social organisation in affecting the importance of female queuing is yet to be studied, but will likely depend on the strength of social control by the dominant members of the group. PMID- 27413643 TI - What Would Be a Better Strategy for National University Hospital Management? PMID- 27413644 TI - Development of Financial Support Program for High Risk Pregnant Women. AB - OBJECTIVES: The purpose of this study was to develop a financial support program for high-risk pregnant women based on opinions obtained using a questionnaire survey. METHODS: The program development involved two steps: (1) developing a questionnaire through reviewing previous financial support programs for maternal care and then validating it via professional consultation; and (2) drafting a financial support program. Sixty professionals, 26 high-risk pregnant women, and 100 program implementers completed the questionnaire between August 2014 and October 2014. RESULTS: Based on the obtained professional consultation and survey investigation, the framework of the financial support program was constructed. The suggested recipients were mothers with early labor pains, mothers who have been hospitalized for > 3 weeks, and mothers who used uterine stimulant Pitocin during hospitalization. All hospitalization, medication, and examination costs needed to be supported considering the income level of the recipient. CONCLUSION: A basic policy for financially supporting high-risk pregnant women has been developed. The efficacy and feasibility of the policy needs to be carefully examined in future studies. PMID- 27413642 TI - Tumor Suppressors and Endodermal Differentiation of P19 Embryonic Stem Cells. PMID- 27413645 TI - Competitive Strategy for Successful National University Hospital Management in the Republic of Korea. AB - OBJECTIVES: This study provides information to aid decision making for managers and the staff of national university hospitals through analyzing their financial statements. METHODS: In order to analyze the finances of national university hospitals, this study used the report of final accounts announced by each hospital from 2009 to 2012 as baseline data. The research participants were 10 national university hospitals. RESULTS: According to the results of the analysis, most hospitals (except for a few) had medical expenses exceeding their medical revenues, resulting in a net deficit; however, there were significant differences amongst the hospitals. The result of adjustments based on a standard size of 100 beds showed that most hospitals had medical revenue deficits, and there were significant differences between hospitals in terms of medical revenues and medical costs. CONCLUSION: It is not clear whether an expansion of national university hospitals is always beneficial for increasing net revenues, and it is necessary to establish a differentiation strategy to increase profitability by securing financial soundness instead of externally-oriented growth. PMID- 27413646 TI - Epidemiological and Clinical Features of People with Malta Fever in Iran: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: Numerous studies have reported the epidemiological and clinical features of Malta fever incidence in Iran. Review and synthesis of the related literature through meta-analysis can provide an appropriate measurement for aforementioned indices. Therefore, the present study aimed to determine the epidemiological and clinical features of people with Malta fever in Iran. METHODS: The required documents were obtained through searching national and international databases. In each study, standard deviation of the indices was calculated using binomial distribution formulas. Finally, the heterogeneity index was determined between studies using Cochran (Q) and I (2) tests. RESULTS: Combining the results of 47 articles in the meta-analysis indicated that 57.6% (55.02-60.1%) and 42.3% (49.8-44.9%) of the patients were male and female, respectively. Most of the patients lived in rural areas; 68.4% (63.6-73.2%) compared to 31.4% (26.7-36.3%). In addition, 20.8% (17.4-24.2%) of the patients were ranchers and farmers, 16.9% (14.5-19.4%) were students, and 31.6% (27-36.2%) were housewives. Of the patients studies, 50.5% (35.6-65.2%) experienced contact with animals and 57.1% (46.4-67.9%) used unpasteurized dairy products. Fever, joint pain, and sweating were detected among 65.7% (53.7-77.8%) and 55.3% (44.4 66.2%), respectively. CONCLUSION: The present study revealed that the frequency of male patients with brucellosis was considerably more than that of female patients. The number of patients with Malta fever in rural areas was significantly more than in urban areas. High-risk behavior, unprotected contact with animals, and using unpasteurized dairy products were among the most significant factors affecting Malta fever incidence in Iran. Fever, joint pain, and sweating were detected among most of the patients with Malta fever. PMID- 27413647 TI - Study on Seroprevalence and Leptospiral Antibody Distribution among High-risk Planters in Malaysia. AB - OBJECTIVES: To determine the leptospirosis seroprevalence and to identify the predominant infecting serovars among oil palm plantation workers. METHODS: The cross-sectional study involved 350 asymptomatic oil palm plantation workers in Melaka and Johor. A serological test using the microscopic agglutination test was conducted in the Institute of Medical Research with a cut-off titre for seropositivity of >=1:100. RESULTS: The overall seroprevalence of leptospiral antibodies was 28.6%. The job category with the highest seroprevalence was the fruit collector with 59.2%. The predominant serovar identified was serovar Sarawak (Lepto 175) (62%). CONCLUSION: A high seroprevalence of leptospiral antibodies was detected among oil palm plantation workers and specifically among fruit collectors. The predominant infecting serovar among the workers was serovar Sarawak (Lepto 175). The findings suggest that more studies are needed to determine the reasons for the high seroprevalence and the transmission and pathogenicity of the local serovar Sarawak (Lepto 175). PMID- 27413648 TI - Association between Pollen Risk Indexes, Air Pollutants, and Allergic Diseases in Korea. AB - OBJECTIVES: This study, different from the past researches, has been conducted in all age groups to understand the association between air pollutants, pollen risk indexes, and outpatients with allergic rhinitis (AR), asthma, and atopic dermatitis (AD). METHODS: Data on air pollutants, pollen risk indexes, and outpatients with each disease were collected from 2003 through 2011 to verify the association between them. All data are time-series materials that have been observed by time (day) and region, and are in a nonlinear shape. In particular, the total number of outpatients per day is a count data that had a Poisson distribution as the response variable. SAS 9.3 was used to make a statistical model, generalized additive model, with lag effects for the analysis. RESULTS: For allergic diseases during spring (April-May) and fall (September-October), a significant association was shown between the variables of air pollutants, pollens, and the number of outpatients. Especially, the estimates of NO2 [AR (43.00967 +/- 0.11284), asthma (52.01837 +/- 0.06452), AD (52.01837 +/- 0.06452), p < 0.001] in spring and SO2 [AR (43.00967 +/- 0.11284), asthma (52.01837 +/- 0.06452), AD (52.01837 +/- 0.06452), p < 0.001] in fall were highly significant and showed a positive association with all diseases. CONCLUSION: Domestically and even internationally, various studies on the allergic diseases are being conducted. However, not many studies related to similar studies. In the need of creating grounds to back up these efforts, additional studies on allergic diseases, as well as researches utilizing pollen data, air pollution data, and claims data provided by the Health Insurance Corporation that has no problem in the representativeness of the data that have close relationships to the allergic disease will be needed. PMID- 27413649 TI - Intake Trends of Red Meat, Alcohol, and Fruits and Vegetables as Cancer-Related Dietary Factors from 1998 to 2009. AB - OBJECTIVES: Cancer is the leading cause of death worldwide, and cancer incidence and mortality have been increasing steadily in South Korea. This study aimed to examine the change in consumption of three cancer-related dietary factors-red meat, alcohol, and fruits/vegetables, and to evaluate consumption of these dietary factors among Koreans according to the criteria from the recommendations of the World Cancer Research Fund/American Institute of Cancer Research. METHODS: Consumption of red meat, alcoholic beverages, and fruits and vegetables was calculated from the 24-hour recall data of 36,486 individuals older than 20 years who were selected from the Korea National Health and Nutrition Examination Survey 1998-2009. The intake adequacy of these three factors was evaluated by the recommended criteria of the World Cancer Research Fund/American Institute of Cancer Research report. RESULTS: The mean red meat intake in the men in their 20s increased sharply (from 91.6 g to 111.3 g, p < 0.05). The mean alcohol intake increased continuously in men (from 10.3 g to 20.0 g, p < 0.05) and women (from 1.5 g to 3.5 g, p < 0.05). The mean fruit/vegetable intake decreased in the 21-29 year age group (from 349.4 g to 306.7 g in men; from 393.3 g to 292.5 g in women; p < 0.05). The percentage of individuals who did not meet the intake criteria for the three cancer-related dietary factors was especially high, and the percentage increased over 10 years in those in their 20s (p < 0.05). CONCLUSION: We confirmed that intakes of red meat, alcoholic drink, and fruits and vegetables have moved toward a negative direction in both men and women in their 20s. PMID- 27413650 TI - The Mediating Role of Organizational Learning in the Relationship of Organizational Intelligence and Organizational Agility. AB - OBJECTIVES: Organizational learning is defined as creating, absorbing, retaining, transferring, and application of knowledge within an organization. This article aims to examine the mediating role of organizational learning in the relationship of organizational intelligence and organizational agility. METHODS: This analytical and cross-sectional study was conducted in 2015 at four teaching hospitals of Yazd city, Iran. A total of 370 administrative and medical staff contributed to the study. We used stratified-random method for sampling. Required data were gathered using three valid questionnaires including Alberkht (2003) organizational intelligence, Neefe (2001) organizational learning, and Sharifi and Zhang (1999) organizational agility questionnaires. Data analysis was done through R and SPSS 18 statistical software. RESULTS: The results showed that organizational learning acts as a mediator in the relationship of organizational intelligence and organizational agility (path coefficient = 0.943). Also, organizational learning has a statistical relationship with organizational agility (path coefficient = 0.382). CONCLUSION: Our findings suggest that the improvement of organizational learning abilities can affect an organization's agility which is crucial for its survival. PMID- 27413651 TI - Comparing Performance Indicators of Obstetrics and Gynecology Ward at Yazd Educational Hospitals with Expected Limits of Indicators, 2015. AB - OBJECTIVES: The purpose of this study was to evaluate the performance indicators for obstetrics and gynecology wards in Iran. METHODS: This study was designed as a cross-sectional study and was carried out in obstetrics and gynecology wards of Afshar and Shahid Sadoughi hospitals in 2015. The information required for the performance indicators was gathered through questionnaires, statistical forms, and direct observation. In several tables, performance rating and performance status are presented using the Likert scale index based on the expected limits. RESULTS: According to the results of the categories of input indicators, the bed occupancy rate of Afshar Hospital's obstetrics and gynecology ward was, at 83%, higher than expected (79%), and that in Shahid Sadoughi Hospital (at 69%) was lower than expected. For medicinal methods and nonmedicinal methods of pain alleviation, the index process at Afshar Hospital was much lower than expected (40%). In Afshar Hospital, patient satisfaction at discharge was about 66.74%. CONCLUSION: Effective steps can be taken to improve the input and output criteria: allocating appropriate physical space, examining the reasons for low bed occupancy rate by using complex analytical models, and in order to study the reasons for large number of cesarean section childbirth, it was recommended to place more emphasis on training of pregnant mothers and to inform them about the side effects of cesarean section and advantages of natural childbirth. PMID- 27413652 TI - One-Step Reverse Transcription-Polymerase Chain Reaction for Ebola and Marburg Viruses. AB - OBJECTIVES: Ebola and Marburg viruses (EBOVs and MARVs, respectively) are causative agents of severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. In 2014, there was a major Ebola outbreak in various countries in West Africa, including Guinea, Liberia, Republic of Sierra Leone, and Nigeria. EBOV and MARV are clinically difficult to diagnose and distinguish from other African epidemic diseases. Therefore, in this study, we aimed to develop a method for rapid identification of the virus to prevent the spread of infection. METHODS: We established a conventional one-step reverse transcription polymerase chain reaction (RT-PCR) assay for these pathogens based on the Superscript Reverse Transcriptase-Platinum Taq polymerase enzyme mixture. All assays were thoroughly optimized using in vitro-transcribed RNA. RESULTS: We designed seven primer sets of nucleocapsid protein (NP) genes based on sequences from seven filoviruses, including five EBOVs and two MARVs. To evaluate the sensitivity of the RT-PCR assay for each filovirus, 10-fold serial dilutions of synthetic viral RNA transcripts of EBOV or MARV NP genes were used to assess detection limits of viral RNA copies. The potential for these primers to cross react with other filoviruses was also examined. The results showed that the primers were specific for individual genotype detection in the examined filoviruses. CONCLUSION: The assay established in this study may facilitate rapid, reliable laboratory diagnosis in suspected cases of Ebola and Marburg hemorrhagic fevers. PMID- 27413653 TI - Leisure-time activities and psychological distress in a suburban community in Japan. AB - OBJECTIVE: There is a wide range of leisure-time activities and previous research indicates that some of these are associated with lower psychological distress. The aim of this study was to assess whether leisure-time activities were associated with psychological distress. METHODS: A population-based questionnaire survey was conducted in 2009 in a suburban area of northern Japan using complete enumeration. Of 16,996 residents aged 30-79 years who received the questionnaire, 14,261 (83.9%) responded and 9908 (58.3%) responses were eligible for analysis. The relationship between psychological distress and physical, artistic, outdoor, and volunteer leisure-time activities was assessed separately and simultaneously by sex. RESULTS: The percentage of reported psychological distress was 2.8% for men and 3.9% for women. Each category of leisure-time activity was related to psychological distress separately. The simultaneous analyses revealed that engaging in regular outdoor leisure activity was associated with less psychological distress in both men (odds ratio [OR] = 0.38; 95% confidence intervals [CI]: 0.23, 0.63, p < 0.001) and women (OR = 0.39; 95% CI: 0.25, 0.59, p < 0.001). Engaging in regular physical activity was associated with less psychological distress in women (OR = 0.09; 95% CI: 0.01, 0.68, p = 0.019). Volunteer work and art activities were not associated with psychological distress in either men or women. CONCLUSION: Greater engagement in outdoor leisure activity and physical activity was significantly associated with a lower likelihood of psychological distress. The results from the present study indicate that engaging in leisure-time activities, especially in outdoor leisure and physical activities, may be an effective means of promoting public health. PMID- 27413655 TI - American preferences for "smart" guns versus traditional weapons: Results from a nationwide survey. AB - This study examines Americans' preferences regarding smart guns. The study builds on prior research by including previously unexamined factors, specifically victimization and comfort sharing gun ownership status with a doctor. Further, this study examines differences in preference patterns among gun owners and non owners. Data were obtained from a nationwide online survey with 524 respondents in February 2016. The study finds that, among non-owners, older respondents and those with pro-gun attitudes are less likely to prefer smart guns to traditional firearms. Among gun owners, those with moderate political views, those with a history of victimization, and those residing in the Northeast are all more likely to prefer smart guns. Males and those with pro-gun attitudes are less likely to prefer smart guns. Education, income, race, marital status, presence of children in the home, and comfort discussing gun ownership with a doctor had no significant association with smart gun preference. Practical implications of these findings are discussed. PMID- 27413654 TI - Tailored information increases patient/physician discussion of colon cancer risk and testing: The Cancer Risk Intake System trial. AB - Assess whether receipt of tailored printouts generated by the Cancer Risk Intake System (CRIS) - a touch-screen computer program that collects data from patients and generates printouts for patients and physicians - results in more reported patient-provider discussions about colorectal cancer (CRC) risk and screening than receipt of non-tailored information. Cluster-randomized trial, randomized by physician, with data collected via CRIS prior to visit and 2-week follow-up telephone survey among 623 patients. Patients aged 25-75 with upcoming primary care visits and eligible for, but currently non-adherent to CRC screening guidelines. Patient-reported discussions with providers about CRC risk and testing. Tailored recipients were more likely to report patient-physician discussions about personal and familial risk, stool testing, and colonoscopy (all p < 0.05). Tailored recipients were more likely to report discussions of: chances of getting cancer (+ 10%); family history (+ 15%); stool testing (+ 9%); and colonoscopy (+ 8%) (all p < 0.05). CRIS is a promising strategy for facilitating discussions about testing in primary-care settings. PMID- 27413656 TI - Age-related patterns of vigorous-intensity physical activity in youth: The International Children's Accelerometry Database. AB - Physical activity declines during youth but most evidence reports on combined moderate and vigorous-intensity physical activity. We investigated how vigorous intensity activity varies with age. Cross-sectional data from 24,025 participants (5.0-18.0 y; from 20 studies in 10 countries obtained 2008-2010) providing >= 1 day accelerometer data (International Children's Accelerometry Database (ICAD)). Linear regression was used to investigate age-related patterns in vigorous intensity activity; models included age (exposure), adjustments for monitor wear time and study. Moderate-intensity activity was examined for comparison. Interactions were used to investigate whether the age/vigorous-activity association differed by sex, weight status, ethnicity, maternal education and region. A 6.9% (95% CI 6.2, 7.5) relative reduction in mean vigorous-intensity activity with every year of age was observed; for moderate activity the relative reduction was 6.0% (5.6%, 6.4%). The age-related decrease in vigorous-intensity activity remained after adjustment for moderate activity. A larger age-related decrease in vigorous activity was observed for girls (- 10.7%) versus boys (- 2.9%), non-white (- 12.9% to - 9.4%) versus white individuals (- 6.1%), lowest maternal education (high school (- 2.0%)) versus college/university (ns) and for overweight/obese (- 6.1%) versus healthy-weight participants (- 8.1%). In addition to larger annual decreases in vigorous-intensity activity, overweight/obese individuals, girls and North Americans had comparatively lower average vigorous-intensity activity at 5.0-5.9 y. Age-related declines in vigorous-intensity activity during youth appear relatively greater than those of moderate activity. However, due to a higher baseline, absolute moderate-intensity activity decreases more than vigorous. Overweight/obese individuals, girls, and North Americans appear especially in need of vigorous-intensity activity promotion due to low levels at 5.0-5.9 y and larger negative annual differences. PMID- 27413658 TI - Associations with E-cigarette use among Asian American and Pacific Islander young adults in California. AB - With attention to the rapidly growing market of electronic nicotine delivery systems (ENDS/e-cigarettes) and the fastest growing US ethnic minority group, the current study explored associations between awareness, perceived risks, and use of ENDS among Asian American and Pacific Islander (AAPI) young adults. AAPI young adults (ages 18-25) in California were recruited via social media, college classes, listservs for AAPI-serving non-profits, and snowball sampling to complete an anonymous survey between 2014 and 2015. The sample (N = 501) was 57% women, 15% LGBTQIA; with a mean age of 21; 26% foreign-born; identifying as Filipino (29%), Chinese (24%), Vietnamese (14%), mixed-AAPI heritage (13%), or 21% other. Nearly half the sample (44%) reported ever ENDS use; 11% were current users. Current ENDS use was twofold greater for: Filipino and Vietnamese compared to Chinese respondents; men versus women; LGBTQIA-identified respondents; those vocationally trained; and employed. Awareness of ENDS from peers/friends was most common and was associated with ever though not current ENDS use. Most respondents perceived ENDS as harmful (62%); low compared to high risk perception was associated with a three-fold greater likelihood of ever use and six-fold greater likelihood of current use. Popular flavors were fruit (49%, e.g., lychee, taro) and candy/sweets (26%). Current users viewed ENDS as a healthier alternative or quit aid for conventional cigarettes (42%); recreation/social use (33%) also was common. Findings indicate ENDS visibility among AAPI young adults in California with affinity for flavors and many engaging in trial and current use for harm reduction and recreational/social aims. PMID- 27413657 TI - An evidence-based conceptual framework of healthy cooking. AB - Eating out of the home has been positively associated with body weight, obesity, and poor diet quality. While cooking at home has declined steadily over the last several decades, the benefits of home cooking have gained attention in recent years and many healthy cooking projects have emerged around the United States. The purpose of this study was to develop an evidence-based conceptual framework of healthy cooking behavior in relation to chronic disease prevention. A systematic review of the literature was undertaken using broad search terms. Studies analyzing the impact of cooking behaviors across a range of disciplines were included. Experts in the field reviewed the resulting constructs in a small focus group. The model was developed from the extant literature on the subject with 59 studies informing 5 individual constructs (frequency, techniques and methods, minimal usage, flavoring, and ingredient additions/replacements), further defined by a series of individual behaviors. Face validity of these constructs was supported by the focus group. A validated conceptual model is a significant step toward better understanding the relationship between cooking, disease and disease prevention and may serve as a base for future assessment tools and curricula. PMID- 27413659 TI - Determinants of participation in a cardiometabolic health check among underserved groups. AB - Cardiometabolic diseases affect underserved groups disparately. Participation in health checks is also lower, widening health inequalities in society. Two-stage screening (non-invasive health risk assessment (HRA) and GP consultations for high-risk individuals) seems cost-effective, provided that drop-out rates are low in both steps. We aimed to explore the process of decision-making regarding HRA participation among underserved groups (45-70 y): native Dutch with a lower socioeconomic status (SES), Turkish, Moroccan, and Surinamese participants. We conducted a cross-sectional questionnaire study. The questionnaire comprised the following determinants: a self-formulated first reaction, a structured set of predefined determinants, and the most important barrier(s) and facilitator(s) for HRA completion. We used univariable and (stepwise) multivariate logistic regression analyses to assess which determinants were associated with HRA completion. Of the 892 participants in the questionnaire, 78% (n = 696) also completed the HRA. Moroccans and patients from GP practices with a predominantly non-Western population less often completed the HRA. A lower SES score, wanting to know one's risk, not remembering receiving the invitation (thus requiring a phone call), fear of the test result and/or adjusting lifestyle, perceived control of staying healthy, wanting to participate, and perceiving no barriers were associated with completing the HRA. We conclude that our 'hard-to-reach' population may not be unwilling to participate in the HRA. A more comprehensive approach, involving key figures within a community informing people about and providing help completing the HRA, would possibly be more suitable. Efforts should be particularly targeted at the less acculturated immigrants with an external locus of control. PMID- 27413660 TI - Physical activity pattern, cardiorespiratory fitness, and socioeconomic status in the SCAPIS pilot trial - A cross-sectional study. AB - Living in a low socioeconomic status (SES) area is associated with an increased risk of cardiovascular events and all-cause mortality. Previous studies have suggested a socioeconomic gradient in daily physical activity (PA), but have mainly relied on self-reported data, and individual rather than residential area SES. This study aimed to investigate the relationships between residential area SES, PA pattern, compliance with PA-recommendations and fitness in a Swedish middle-aged population, using objective measurements. We included 948 individuals from the SCAPIS pilot study (Gothenburg, Sweden, 2012, stratified for SES, 49% women, median age: 58 years), in three low and three high SES districts. Accelerometer data were summarized into intensity-specific categories: sedentary (SED), low (LIPA), and medium-to-vigorous PA (MVPA). Fitness was estimated by submaximal ergometer testing. Participants of low SES areas had a more adverse cardiovascular disease risk factor profile (smoking: 20% vs. 6%; diabetes: 9% vs. 3%; hypertension: 38% vs. 25%; obesity: 31% vs. 13%), and less frequently reached 150 min of MVPA per week (67% vs. 77%, odds ratio [OR] = 0.61; 95% confidence interval [95% CI] = 0.46-0.82), from 10-minute bouts (19% vs. 31%, OR = 0.53, 95% CI = 0.39-0.72). Individuals in low SES areas showed lower PA levels (mean cpm: 320 vs. 348) and daily average MVPA (29.9 vs. 35.5 min), and 12% lower fitness (25.1 vs. 28.5 mL * min(- 1) * kg(- 1)) than did those in high SES areas. Reduced PA and fitness levels may contribute to social inequalities in health, and should be a target for improved public health in low SES areas. PMID- 27413661 TI - Use of new guidance to profile 'equivalent minutes' of aerobic physical activity for adults in England reveals gender, geographical, and socio-economic inequalities in meeting public health guidance: A cross-sectional study. AB - English physical activity guidance now recognises a double weighting of vigorous over moderate activity; 1 min of vigorous activity is the same as two 'equivalent' minutes of moderate activity. In addition, concerns of over estimation of occupational PA led to newly applied measurement methods for this domain. Vigorous activity is associated with higher socio-economic position and occupational PA has the opposite association, so these changes may increase inequalities. We profiled adults' total and domain-specific 'equivalent minutes' of weekly PA in England 2012, and investigated inequalities in PA participation, accounting for the new weighting of vigorous PA, and new measurements of occupational PA. Nationally representative cross-sectional survey data on the self-reported PA of 8158 adults was used to produce a profile of the domain and duration of weekly 'equivalent minutes' of PA. Vigorous PA was double-weighted compared to moderate PA, and the percentage contribution from each PA domain quantified, stratified by gender and activity status and split by socio demographic variables. Women, older adults, and adults without qualifications, from deprived areas, with worse employment conditions, or living in the North of England were significantly less likely to meet MVPA guidance. Type of activity was also socially patterned, particularly sport participation, which contributed a higher percentage of PA in adults of higher socioeconomic status. For active men, sporting activity was the most prevalent domain, and sports and walking for active women. In England, there are important socio-demographic differences in how adults participate in PA, and in percentage meeting public health guidance. PMID- 27413662 TI - Occupational status and job stress in relation to cardiovascular stress reactivity in Japanese workers. AB - This study aimed to investigate the effects of occupational status and job stress factors on cardiovascular stress reactivity in Japanese workers. In this baseline assessment between 2001 and 2009 in Osaka, Japan, we examined 928 healthy Japanese employees (330 men, 598 women) from two occupational statuses: managers/professionals and general workers. A brief job stress questionnaire was used to evaluate job stress levels. Systolic and diastolic blood pressure (SBP, DBP), heart rate, heart rate variability (high-frequency [HF], low-frequency [LF], LF/HF], and peripheral blood flow were measured at rest and during two stressful tasks. Changes in stress reactivity were calculated as the difference between the measured variables during the tasks and the rest period. Men showed inverse associations between quantitative job overload and DBP, heart rate, and LF/HF, between physical demands and blood pressure (SBP, DBP), and between a poor physical environment and HF. Men also had positive associations between qualitative job overload and heart rate, and between physical demands and peripheral blood flow (all p < 0.05). Women showed inverse associations between qualitative job overload and SBP, and showed positive associations between qualitative job overload and peripheral blood flow, and between a poor physical environment and SBP (all p < 0.05). When stratified by occupational status, significant associations between job stress and changes in stress reactivity were observed in male managers/professionals and female general workers (p < 0.05). Job stress levels are associated with changes in cardiovascular stress reactivity in men and women. Occupational status may modify these associations. PMID- 27413663 TI - The impact of area residential property values on self-rated health: A cross sectional comparative study of Seattle and Paris. AB - This study analyzed the impact of area residential property values, an objective measure of socioeconomic status (SES), on self-rated health (SRH) in Seattle, Washington and Paris, France. This study brings forth a valuable comparison of SRH between cities that have contrasting urban forms, population compositions, residential segregation, food systems and transportation modes. The SOS (Seattle Obesity Study) was based on a representative sample of 1394 adult residents of Seattle and King County in the United States. The RECORD Study (Residential Environment and Coronary Heart Disease) was based on 7131 adult residents of Paris and its suburbs in France. Socio-demographics, SRH and body weights were obtained from telephone surveys (SOS) and in-person interviews (RECORD). All home addresses were geocoded using ArcGIS 9.3.1 (ESRI, Redlands, CA). Residential property values were obtained from tax records (Seattle) and from real estate sales (Paris). Binary logistic regression models were used to test the associations among demographic and SES variables and SRH. Higher area property values significantly associated with better SRH, adjusting for age, gender, individual education, incomes, and BMI. The associations were significant for both cities. A one-unit increase in body mass index (BMI) was more detrimental to SRH in Seattle than in Paris. In both cities, higher area residential property values were related to a significantly lower obesity risk and better SRH. Ranked residential property values can be useful for health and weight studies, including those involving social inequalities and cross-country comparisons. PMID- 27413664 TI - Gender and age differences in walking for transport and recreation: Are the relationships the same in all neighborhoods? AB - INTRODUCTION: Walking as regular physical activity (PA) is central to healthy aging, and environments influence walking. Multilevel neighborhood-based studies that only report average (fixed-effect) walking differences for gender and age implicitly assume that neighborhood environments influence the walking behavior of men and women, and younger and older persons, similarly. This study tests this assumption by examining whether gender and age differences in walking for transport (WfT) and walking for recreation (WfR) are similar or different across neighborhoods. METHODS: This paper used data from the HABITAT multilevel study, with 7,866 participants aged 42-68 years in 2009 living in 200 neighborhoods in Brisbane, Australia. Respondents reported minutes spent WfT and WfR in the previous week, categorized as: none (0 mins), low (1-59mins), moderate (60 149mins) and high (>= 150 mins). Multilevel multinomial logistic models were used to estimate average differences in walking by gender and age, followed by random coefficients to examine neighborhood variation in these individual-level relationships. RESULTS: On average, women were more likely to engage in WfR at moderate and high levels (no gender differences found in WfT); and older persons were less likely to do WfT and more likely to do high levels of WfR. These average (Brisbane-wide) relationships varied significantly across neighborhoods. CONCLUSION: Relationships between gender and walking, and age and walking, are not the same in all neighborhoods, (i.e. the Brisbane average conceals important information) suggesting that neighborhood-level factors differentially influence the walking behaviors of men and women and younger and older persons. Identifying these factors should be a priority for future research. PMID- 27413665 TI - Untreated hypertension in the UK household population - Who are missed by the general health checks? AB - Hypertension is an age-related, long-term condition and a leading risk factor for premature death and disability worldwide. Due to its asymptomatic nature it can often be left undiagnosed. Long-term treatment is available, but blood pressure can also be reduced through health behaviour changes in weight control, smoking cessation, higher physical activity levels, reduced salt and alcohol intake, and healthful diets if discovered early. This paper investigates the prevalence and characteristics of those with untreated (compared to treated) hypertension who did not have a history of cardiovascular disease (CVD); a group who is in effect missed by general health checks. Untreated hypertension was studied in 8933 individuals aged 40-74 years representative of the UK household population, who were interviewed and underwent a physical health examination in their home, 2010 2012. The prevalence of untreated hypertension without a history of CVD was 7% for men, 2% for women, and 5% overall. Untreated hypertension was particularly high among the 55-64 year age group. Age and sex-adjusted analyses found strong positive associations with male gender, smoking, self-reported good-excellent health, full fat dairy preference, white bread preference, higher alcohol consumption, and living alone. Strong negative associations were found for possessing 5 + prescription drugs, statins or antiplatelets, being diagnosed with diabetes or possessing antidiabetics, and long-term limiting illness status. Notably, many reported their health as good to excellent. A fact which emphasises the importance of motivating individuals to take part in the general health checks for an asymptomatic condition such as hypertension. PMID- 27413666 TI - Impact of work-related cancers in Taiwan-Estimation with QALY (quality-adjusted life year) and healthcare costs. AB - This study estimates the annual numbers of eight work-related cancers, total losses of quality-adjusted life years (QALYs), and lifetime healthcare expenditures that possibly could be saved by improving occupational health in Taiwan. Three databases were interlinked: the Taiwan Cancer Registry, the National Mortality Registry, and the National Health Insurance Research Database. Annual numbers of work-related cancers were estimated based on attributable fractions (AFs) abstracted from a literature review. The survival functions for eight cancers were estimated and extrapolated to lifetime using a semi-parametric method. A convenience sample of 8846 measurements of patients' quality of life with EQ-5D was collected for utility values and multiplied by survival functions to estimate quality-adjusted life expectancies (QALEs). The loss-of-QALE was obtained by subtracting the QALE of cancer from age- and sex-matched referents simulated from national vital statistics. The lifetime healthcare expenditures were estimated by multiplying the survival probability with mean monthly costs paid by the National Health Insurance for cancer diagnosis and treatment and summing this for the expected lifetime. A total of 3010 males and 726 females with eight work-related cancers were estimated in 2010. Among them, lung cancer ranked first in terms of QALY loss, with an annual total loss-of-QALE of 28,463 QALYs and total lifetime healthcare expenditures of US$36.6 million. Successful prevention of eight work-related cancers would not only avoid the occurrence of 3736 cases of cancer, but would also save more than US$70 million in healthcare costs and 46,750 QALYs for the Taiwan society in 2010. PMID- 27413667 TI - "You're never really off time": Healthcare providers' interpretations of optimal timing for HPV vaccination. AB - Healthcare providers have a strong influence on human papillomavirus (HPV) vaccination decisions, yet they often fail to recommend the vaccine to the 11- and 12-year-olds who are targeted by practice guidelines. We sought to understand how providers interpret and value age-based guidelines. We conducted a secondary analysis of data from two qualitative studies of healthcare providers' HPV vaccination attitudes and practices. Participants were physicians, nurse practitioners, and physician assistants in Minnesota (n = 27) and in Washington (n = 17) interviewed in 2012 and 2014 respectively. Verbatim transcripts from each study were analyzed independently using content analysis, and collective findings were then jointly analyzed. The research team worked via consensus to derive codes and describe representative themes. A high proportion of providers reported either a lack of concern about HPV vaccine completion, or concern beginning several years past the recommended target age. Many providers perceived a gradient of HPV vaccination timeliness ranging from age 12 to 26. Instead of age-based recommendations, providers timed recommendations based on perceptions of access to care and patient risk. They often offered "gentle" recommendations and deferred vaccination discussions as a tool to building trust with families. Interventions aimed at helping providers deliver effective recommendations for timely HPV vaccination are needed. Our findings suggest that changing the norm of provider culture to one in which "catch-up" schedules are seen as a suboptimal way to achieve vaccine uptake may be an important goal. PMID- 27413668 TI - Factors associated with early adoption of the HPV vaccine in US male adolescents include Hispanic ethnicity and receipt of other vaccines. AB - Adolescent males' HPV vaccine initiation and completion in the United States is far below the Healthy People 2020 goal of 80% 3-dose completion among boys. In 2012, less than 7% of males ages 13-17 years had completed the 3-dose series. The Diffusion of Innovations framework guided this investigation of factors related to early adoption of HPV vaccination among male adolescents. Provider-validated data from the 2012 National Immunization Survey-Teen (NIS-Teen) for male adolescents ages 13-17 years were analyzed via a multivariable Poisson regression to estimate prevalence ratios for factors associated with HPV vaccine initiation and completion. Adolescent males who are Hispanic and those who are up to date on other recommended adolescent vaccinations were most likely to complete the HPV vaccine. Public health interventions are needed to improve low HPV vaccination rates among adolescent males in the United States. Description of early adopters of the HPV vaccine provides historical context of HPV vaccination acceptance that is needed to inform the design of targeted vaccination interventions to prevent negative HPV-associated outcomes. PMID- 27413669 TI - Reaching consumers: How the tobacco industry uses email marketing. AB - Tobacco companies are restricted from engaging in many traditional forms of marketing. Direct marketing is one way tobacco companies can reach consumers while complying with regulation and avoiding negative public perception. There is little research on this type of opt-in marketing, which includes mail marketing, email marketing, web marketing, and mobile marketing, and its impact is not well understood. This study examined 6990 tobacco company emails received by individuals living in the state of Minnesota, US between January 2010 and May 2015 to determine email frequency by brand. These emails were gathered as part of ongoing surveillance of tobacco industry direct marketing. A subset of these emails received between October 2014 and May 2015 (n = 1646) were content analyzed to identify the purpose of the email communication along with type of product promoted. Tobacco companies use email to communicate with consumers on a regular basis. This communication was observed to be as frequent as nine times per month. Emails are most commonly used to promote contests (54.1%), content on tobacco company websites (39.1%), and tobacco coupons (15.7%). Email promotion of menthol-flavored tobacco products was common and was associated with promotion of coupons. Emails promoting menthol had a 1.9 times higher prevalence of also promoting coupons (95% CI: 1.52-2.37). Little is known about tobacco company email marketing and this study fills an identified research gap. A deeper understanding of this type of marketing is needed in order to counter tobacco industry messaging and advance tobacco control. PMID- 27413670 TI - A pilot randomized trial of technology-assisted goal setting to improve physical activity among primary care patients with prediabetes. AB - Lifestyle behavior changes can prevent progression of prediabetes to diabetes but providers often are not able to effectively counsel about preventive lifestyle changes. We developed and pilot tested the Avoiding Diabetes Thru Action Plan Targeting (ADAPT) program to enhance primary care providers' counseling about behavior change for patients with prediabetes. Primary care providers in two urban academic practices and their patients with prediabetes were recruited to participate in the ADAPT study, an unblinded randomized pragmatic trial to test the effectiveness of the ADAPT program, including a streamlined electronic medical record-based goal setting tool. Providers were randomized to intervention or control arms; eligible patients whose providers were in the intervention arm received the ADAPT program. Physical activity (the primary outcome) was measured using pedometers, and data were gathered about patients' diet, weight and glycemic control. A total of 54 patients were randomized and analyzed as part of the 6-month ADAPT study (2010-2012, New York, NY). Those in the intervention group showed an increase total daily steps compared to those in the control group (+ 1418 vs - 598, p = 0.007) at 6 months. There was also a trend towards weight loss in the intervention compared to the control group (- 1.0 lbs. vs. 3.0 lbs., p = 0.11), although no change in glycemic control. The ADAPT study is among the first to use standard electronic medical record tools to embed goal setting into realistic primary care workflows and to demonstrate a significant improvement in prediabetes patients' physical activity. PMID- 27413671 TI - Adverse childhood experiences, gender, and HIV risk behaviors: Results from a population-based sample. AB - Recent HIV research suggested assessing adverse childhood experiences (ACEs) as contributing factors of HIV risk behaviors. However, studies often focused on a single type of adverse experience and very few utilized population-based data. This population study examined the associations between ACE (individual and cumulative ACE score) and HIV risk behaviors. We analyzed the 2012 Behavioral Risk Factor Surveillance Survey (BRFSS) from 5 states. The sample consisted of 39,434 adults. Eight types of ACEs that included different types of child abuse and household dysfunctions before the age of 18 were measured. A cumulative score of ACEs was also computed. Logistic regression estimated of the association between ACEs and HIV risk behaviors using odds ratio (OR) with 95% confidence intervals (CIs) for males and females separately. We found that ACEs were positively associated with HIV risk behaviors overall, but the associations differed between males and females in a few instances. While the cumulative ACE score was associated with HIV risk behaviors in a stepwise manner, the pattern varied by gender. For males, the odds of HIV risk increased at a significant level as long as they experienced one ACE, whereas for females, the odds did not increase until they experienced three or more ACEs. Future research should further investigate the gender-specific associations between ACEs and HIV risk behaviors. As childhood adversities are prevalent among general population, and such experiences are associated with increased risk behaviors for HIV transmission, service providers can benefit from the principles of trauma informed practice. PMID- 27413672 TI - Physical activity and sport participation: A systematic review of the impact of fatherhood. AB - Moderate to Vigorous Physical Activity (MVPA), including sport participation, is an important component of a healthy lifestyle. Scholars have devoted considerable attention to understanding the impact of parenthood on MVPA, albeit only for women. As the impact of fatherhood on men's lives is drawing more and more scholarly and societal attention, the aim of the current article is to provide an systematic overview of studies examining the impact of fatherhood on MVPA. A systematic review was conducted in Google Scholar, Web of Science and Web of Knowledge, using (combinations of) the search terms: father(hood), parent(hood), exercise, physical activity, sport and leisure time. This resulted in 54 papers reporting differences in MVPA and/or sport between fathers and childless men or within men that became father, of which 13 were included. Our overview of findings suggested that fathers spent less time on MVPA compared with childless men, but that fathers did not differ from their childless counterparts on the subarea of sport participation. Differences in time spent on MVPA were strongest between childless men and fathers with young children (< 6 yrs). Our systematic review revealed that fathers spent less time on MVPA compared to childless men, especially when they had young children. Interestingly, linkages between parental status and the subarea of sport participation were not found, which suggests that fathers cut back on other areas of MVPA. Given the impact of MVPA on a healthy lifestyle, future research in this field is warranted. PMID- 27413673 TI - Abdominal obesity is a risk factor for dysexecutive function in chronic kidney disease. AB - The aim of this study was to assess the influence of the metabolic syndrome and its components on dysexecutive function (DF) in individuals with and without CKD. Among 588 participants aged over 70 from the Einstein Aging Study (EAS), we defined DF as performance of 2SDs below the mean on any one test or 1.5SDs below the mean on any two of the following: Block Design, Digit Symbol Coding and the Trail-making Tests A and B. We defined CKD as an eGFR below 60 mL/min/m(2). MetS was defined according to recent guidelines from the National Cholesterol Education Program. 149 participants had CKD at cross-section, 16.1% of which also showed DF. Of the 439 participants without CKD, 12.3% displayed DF. Abdominal obesity as measured by waist circumference, was an independent risk factor for dysexecutive function in CKD (OR = 14.3, 95%CI = 2.21-91.93, p = 0.005) but not in non-CKD. None of the other MetS components were associated with DF. Results suggested that abdominal obesity, recognized as an integral part of the MetS, is a strong risk factor for DF in individuals with CKD. PMID- 27413674 TI - "Gateway hypothesis" and early drug use: Additional findings from tracking a population-based sample of adolescents to adulthood. AB - To evaluate the consistency of the relationship between early drug use in adolescence and illegal drug use in adulthood as proposed in the "gateway theory" and to determine whether pre-existing depressive symptoms modifies this relationship. We used contractual data from the National Longitudinal Study of Adolescent to Adult health data spanning a 14 year period. We assessed the relationship between gateway drugs at baseline (age 11-20 years) and drug use in adulthood using generalized estimating equation (GEE) regression models. Gateways drugs used in early adolescence were significantly associated with marijuana use, illegal drugs and cocaine in older adolescence, but over time these relationships were not consistent in adulthood. Changes in the pattern of psychoactive drug use were important predictors of drug use in adulthood. A history of higher depressive symptoms was associated with higher frequencies of psychoactive drug use over time. Users of mental health services in adolescence were less likely to use drugs in older adolescence and in adulthood. Relationships between early drug use and later drug use in adulthood cannot be solely explained by the gateway hypothesis. Collectively, adolescent drug prevention and treatment programs should apply theory-based and evidence-proven multisectoral intervention strategies rather than providing a brief counseling on individual's behaviors. This evidence should include understanding that changes in behavior should involve broader analyses of the underlying social context for drug use and in particular the role of the community social norms in driving a group's behaviors. PMID- 27413675 TI - The association between social participation and lower extremity muscle strength, balance, and gait speed in US adults. AB - Social participation is associated with healthy aging, and although associations have been reported between social participation and demographics, no published studies have examined a relationship between social participation and measures amenable to intervention. The purpose was to explore the association between self reported social participation and lower extremity strength, balance, and gait speed. A cross-sectional analysis of US adults (n = 2291; n = 1,031 males; mean +/- standard deviation age 63.5 +/- 0.3 years) from the 2001-2 National Health and Nutrition Examination Survey was conducted. Two questions about self-reported difficulty with social participation were categorized into limited (yes/no). The independent variables included knee extension strength (n = 1537; classified as tertiles of weak, normal, and strong), balance (n = 1813; 3 tests scored as pass/fail), and gait speed (n = 2025; dichotomized as slow [less than 1.0 m/s] and fast [greater than or equal to 1.0 m/s]). Logistic regression, accounting for the complex survey design and adjusting for age, sex, physical activity, and medical conditions, was used to estimate the odds of limitation in social participation with each independent variable. Alpha was decreased to 0.01 due to multiple tests. Slower gait speed was significantly associated with social participation limitation (odds ratio = 3.1; 99% confidence interval: 1.5-6.2). No significant association was found with social participation and lower extremity strength or balance. The odds of having limitation in social participation were 3 times greater in those with slow gait speed. Prospective studies should examine the effect of improved gait speed on levels of social participation. PMID- 27413676 TI - Assessment of occupational risks to extremely low frequency magnetic fields: Validation of an empirical non-expert approach. AB - The expert method of exposure assignment involves relying on chemists or hygienists to estimate occupational exposures using information collected on study subjects. Once the estimation method for a particular contaminant has been made available in the literature, it is not known whether a non-expert, briefly trained by an expert remaining available to answer ad hoc questions, can provide reliable exposure estimates. We explored this issue by comparing estimates of exposure to extremely low frequency magnetic fields (ELF-MF) obtained by an expert to those from a non-expert. Using a published exposure matrix, both the expert and non-expert independently calculated a weekly time-weighted average exposure for 208 maternal jobs by considering three main determinants: the work environment, magnetic field sources, and duration of use or exposure to given sources. Agreement between assessors was tested using the Bland-Altman 95% limits of agreement. The overall mean difference in estimates between the expert and non expert was 0.004 MUT (standard deviation 0.104). The 95% limits of agreement were - 0.20 MUT and + 0.21 MUT. The work environments and exposure sources were almost always similarly identified but there were differences in estimating exposure duration. This occurred mainly when information collected from study subjects was not sufficiently detailed. Our results suggest that following a short training period and the availability of a clearly described method for estimating exposures, a non-expert can cost-efficiently and reliably assign exposure, at least to ELF-MF. PMID- 27413677 TI - Sprint-based exercise and cognitive function in adolescents. AB - Moderate intensity exercise has been shown to enhance cognition in an adolescent population, yet the effect of high-intensity sprint-based exercise remains unknown and was therefore examined in the present study. Following ethical approval and familiarisation, 44 adolescents (12.6 +/- 0.6 y) completed an exercise (E) and resting (R) trial in a counter-balanced, randomised crossover design. The exercise trial comprised of 10 * 10 s running sprints, interspersed by 50 s active recovery (walking). A battery of cognitive function tests (Stroop, Digit Symbol Substitution (DSST) and Corsi blocks tests) were completed 30 min pre-exercise, immediately post-exercise and 45 min post-exercise. Data were analysed using mixed effect models with repeated measures. Response times on the simple level of the Stroop test were significantly quicker 45 min following sprint-based exercise (R: 818 +/- 33 ms, E: 772 +/- 26 ms; p = 0.027) and response times on the complex level of the Stroop test were quicker immediately following the sprint-based exercise (R: 1095 +/- 36 ms, E: 1043 +/- 37 ms; p = 0.038), while accuracy was maintained. Sprint-based exercise had no immediate or delayed effects on the number of items recalled on the Corsi blocks test (p = 0.289) or substitutions made during the DSST (p = 0.689). The effect of high intensity sprint-based exercise on adolescents' cognitive function was dependant on the component of cognitive function examined. Executive function was enhanced following exercise, demonstrated by improved response times on the Stroop test, whilst visuo-spatial memory and general psycho-motor speed were unaffected. These data support the inclusion of high-intensity sprint-based exercise for adolescents during the school day to enhance cognition. PMID- 27413678 TI - Media device ownership and media use: Associations with sedentary time, physical activity and fitness in English youth. AB - The aim of this study was to determine whether ownership and use of electronic media were associated with sedentary time and cardiorespiratory fitness (fitness) in youth. We also aimed to determine if associations were independent of physical activity (PA). Fitness was measured using the 20 m shuttle-run. PA, sedentary time, ownership of media devices and media use were self-reported. Participants (n = 678, age 10-15 years) reported daily sedentary time of 620 (+/- 210) min. Forty-one percent of participants had low PA and 50.4% had low fitness. Higher weekend sedentary time was associated with low fitness in girls (p = 0.005) and boys (p < 0.001) and remained significant when adjusted for PA in the latter (p = 0.006). Using social media was associated with higher sedentary time in both sexes and low fitness in girls. High sedentary time was more likely (OR = 5.3, 95%CI: 2.0-14.4) in boys who owned game consoles. Low fitness was more likely in boys who owned digital/satellite TV receivers (OR = 1.8, 95%CI: 1.8-3.2). Schoolchildren spent > 10 h or ~ 85% of each waking day sedentary. Use of social media was associated with higher sedentary time in both sexes and with low fitness in girls. Reducing social media use in youth offers one potential target for intervention. Behaviours associated with sedentary time differed from predictors of low fitness. The complex and often sex-specific interactions identified between sedentary time, PA and fitness suggest the need for carefully targeted interventions to reduce sedentary time and improve fitness in English youth. PMID- 27413679 TI - Potential health effects of electronic cigarettes: A systematic review of case reports. AB - The health risks associated with electronic cigarettes (ECs) are largely unknown. The purpose of this systematic review was to evaluate published case reports that deal with health effects attributed to EC use. An Internet search was conducted to identify case reports dealing with the effects of EC use on health. Twenty-six case reports representing 27 individuals (one study contained reports for two individuals) were published between April 2012 and January 2016, and these were grouped into categories of effect according to their health outcomes. Of the 27 individuals, 25 had negative effects subsequent to use or exposure to ECs and their refill fluids, while two reported improvement in chronic immune and gastrointestinal conditions. Three categories of negative health effects were identified: systemic effects, nicotine poisoning, and mechanical injury. Thirteen cases reported EC effects on different systems including: respiratory (6), gastrointestinal or developing intestine of an infant (3), cardiovascular (2), neurological (1), and immune (1). Twelve cases involved nicotine poisoning resulting from accidental (N = 3), misuse/abuse (N = 1), or suicidal/intentional ingestion (N = 8); four of these involved children and three resulted in adult fatalities. Two cases reported mechanical injury caused by an EC battery explosion. Most case reports show that the health of children and adults can be negatively affected by EC products and that if death does not occur, negative effects can be reversed. Data further indicate that EC use can cause negative health effects in previously healthy individuals and exacerbate pre-existing conditions. PMID- 27413680 TI - Healthy Volunteer 2020: Comparing Peace Corps Volunteers' health metrics with Healthy People 2020 national objectives. AB - Healthy People 2020 (HP2020) provides a set of quantifiable objectives for improving the health and well-being of Americans. This study examines Peace Corps Volunteers' health metrics in comparison with the Leading Health Indicators (LHIs) in order to set baseline measures for Volunteers' health care and align our measurements with Healthy People 2020 standards. Health data from multiple internal Peace Corps datasets were compared with relevant LHIs and analyzed using descriptive statistics. Seventeen (65%) of the 26 LHIs were relevant to Peace Corps Volunteers. Of these, Volunteers' health measures met or were more favorable than the goals of 13 (76%) of the LHIs. There were no data available for 4 (24%) of the LHIs. The entire Volunteer population has full access to primary care, oral health, and reproductive health services. No suicides or homicides were reported among Volunteers during the analyzed time period. Utilizing the LHIs, we have identified high-priority public health issues relevant for the Peace Corps Volunteer population. We discuss the need for quality data to measure and monitor Volunteers' health progress and outcomes over time, and also to standardize our measurements with Healthy People 2020 benchmarks. This framework may foster greater collaboration to engage in health promotion and disease prevention activities driven by evidence-based information, which may, in turn, encourage healthy behavior among Volunteers. PMID- 27413681 TI - Office workers' objectively assessed total and prolonged sitting time: Individual level correlates and worksite variations. AB - Sedentary behavior is highly prevalent in office-based workplaces; however, few studies have assessed the attributes associated with this health risk factor in the workplace setting. This study aimed to identify the correlates of office workers' objectively-assessed total and prolonged (>= 30 min bouts) workplace sitting time. Participants were 231 Australian office workers recruited from 14 sites of a single government employer in 2012-13. Potential socio-demographic, work-related, health-related and cognitive-social correlates were measured through a self-administered survey and anthropometric measurements. Associations with total and prolonged workplace sitting time (measured with the activPAL3) were tested using linear mixed models. Worksites varied significantly in total workplace sitting time (overall mean [SD]: 79% [10%] of work hours) and prolonged workplace sitting time (42% [19%]), after adjusting for socio-demographic and work-related characteristics. Organisational tenure of 3-5 years (compared to tenure > 5 years) was associated with more time spent in total and prolonged workplace sitting time, while having a BMI categorised as obese (compared to a healthy BMI) was associated with less time spent in total and prolonged workplace sitting time. Significant variations in sitting time were observed across different worksites of the same employer and the variation remained after adjusting for individual-level factors. Only BMI and organisational tenure were identified as correlates of total and prolonged workplace sitting time. Additional studies are needed to confirm the present findings across diverse organisations and occupations. PMID- 27413682 TI - Comparison of serum lipid management between elderly and non-elderly patients with and without coronary heart disease (CHD). AB - Serum lipid management in patients aged >= 75 has not been precisely explored. We, therefore, compared the serum lipid management between the two age groups with and without coronary heart disease (CHD). We, therefore, retrospectively reviewed medical charts of patients who were hospitalized in the departments of internal medicine during a period of 14 months. Serum lipid goal attainment was explored by applying the lipid goals for patients aged < 75 to those aged >= 75. In 1988 enrolled patients, 717 subjects (36.1%) were aged >= 75. Among them, 41.3% and 32.4% of the patients had CHD, 44.2% and 41.0% were primary prevention at high-risk, and 14.5% and 14.6% were primary prevention at moderate-risk in patients aged >= 75 and aged < 75, respectively. Serum LDL-C goal achievement rates in CHD were 66.9% and 65.0% in patients aged >= 75 and < 75, respectively (p = 0.334). In the primary prevention at high-risk, these rates were 73.5% and 63.3%, in patients aged >= 75 and < 75, respectively (p = 0.001). They were 77.9% and 58.1% in primary prevention at moderate-risk aged >= 75 and < 75, respectively (p < 0.001). In CHD, lipid-lowering medication subscription rates were significantly lower in patients aged >= 75 (60.1%) than those aged < 75 (73.8%, p < 0.001). In conclusion, in CHD, serum lipid goal attainment was comparable between the two age groups although the lipid-lowering drugs were less frequently prescribed in patients aged >= 75. Without CHD, it was significantly better in patients aged >= 75 than those aged < 75 although the lipid-lowering drug subscription rates were comparable between the two age groups. PMID- 27413683 TI - Characteristics associated with self-rated health in the CARDIA study: Contextualising health determinants by income group. AB - An understanding of factors influencing health in socioeconomic groups is required to reduce health inequalities. This study investigated combinations of health determinants associated with self-rated health (SRH), and their relative importance, in income-based groups. Cross-sectional data from year 15 (2000 - 2001) of the CARDIA study (Coronary Artery Risk Development in Young Adults, USA) - 3648 men and women (mean 40 years) - were split into 5 income-based groups. SRH responses were categorized as 'higher'/'lower'. Health determinants (medical, lifestyle, and social factors, living conditions) associated with SRH in each group were analyzed using classification tree analysis (CTA). Income and SRH were positively associated (p < 0.05). Data suggested an income-based gradient for lifestyle/medical/social factors/living conditions. Profiles, and relative importance ranking, of multi-domain health determinants, in relation to SRH, differed by income group. The highest ranking variable for each income group was chronic burden-personal health problem (<$25,000); physical activity ($25-50,000; $50-75,000; $100,000 +); and cigarettes/day ($75-100,000). In lower income groups, more risk factors and chronic burden indicators were associated with SRH. Social support, control over life, optimism, and resources for paying for basics/medical care/health insurance were greater (%) with higher income. SRH is a multidimensional measure; CTA is useful for contextualizing risk factors in relation to health status. Findings suggest that for lower income groups, addressing contributors to chronic burden is important alongside lifestyle/medical factors. In a proportionate universalism context, in addition to differences in intensity of public health action across the socioeconomic gradient, differences in the type of interventions to improve SRH may also be important. PMID- 27413684 TI - Physical activity levels in adults with intellectual disabilities: A systematic review. AB - Despite evidence that inactivity is a major factor causing ill health in people with intellectual disabilities (pwID) there are gaps in our knowledge of their physical activity (PA). To date, there is no published systematic review of their PA levels. Therefore, we performed a systematic review from January-October 2015, comprising studies from across the globe to establish PA levels, determine how they were measured, and what factors influenced PA in adults with intellectual disabilities (awID). Five databases were searched. Studies were included if written in English, peer-reviewed, had primary research data, and measured PA levels of awID. Quality was assessed using a 19-item checklist. Meta-summary of the findings was performed and a meta-analysis of factors influencing PA using multiple regression. Fifteen studies were included consisting of 3159 awID, aged 16-81 years, 54% male and 46% female. Only 9% of participants achieved minimum PA guidelines. PA levels were measured using objective and subjective methods. ID severity, living in care, gender, and age were independently significantly correlated with the number of participants achieving PA guidelines with the strongest predictor being ID severity (Beta 0.631, p < 0.001). Findings should be in the context that most of the participants were in the mild/moderate range of ID severity and none of the studies objectively measured PA in people with profound ID. To inform measurement and intervention design for improved PA, we recommend that there is an urgent need for future PA studies in awID population to include all disability severity levels. PROSPERO registration number CRD42015016675. PMID- 27413685 TI - Identifying and mitigating risks for agricultural injury associated with obesity. AB - In some occupational contexts overweight and obesity have been identified as risk factors for injury. The purpose of this study was to examine this hypothesis within farm work environments and then to identify specific opportunities for environmental modification as a preventive strategy. Data on farm-related injuries, height and weight used to calculate body mass index (BMI), and demographic characteristics were from the Phase 2 baseline survey of the Saskatchewan Farm Injury Cohort; a large cross-sectional mail-based survey conducted in Saskatchewan, Canada from January through May 2013. Multivariable logistic regression was used to examine associations between BMI and injury. Injury narratives were explored qualitatively. Findings were inconsistent and differed according to gender. Among women (n = 927), having overweight (adjusted OR: 2.94; 95% CI: 1.29 to 6.70) but not obesity (1.10; 95% CI: 0.35 to 3.43) was associated with an increased odds of incurring a farm-related injury. No strong or statistically significant effects were observed for men (n = 1406) with overweight or obesity. While injury-related challenges associated with obesity have been addressed in other occupational settings via modification of the worksite, such strategies are challenging to implement in farm settings because of the diversity of work tasks and associated hazards. We conclude that the acute effects of overweight in terms of injury do require consideration in agricultural populations, but these should also be viewed with a differentiation based on gender. PMID- 27413686 TI - Lifetime cigarette smoking is associated with abdominal obesity in a community based sample of Japanese men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA). AB - Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men. From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40-64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups. We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two thirds showed body mass index (BMI) < 25 kg/m(2) (median, 23.5 kg/m(2)). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001-0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009-0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated. PMID- 27413687 TI - Ethnicity, socioeconomic status, and overweight in Asian American adolescents. AB - Asian American children and adolescents are an under-investigated subpopulation in obesity research. This study aimed to identify specific profiles of Asian subgroups at high risk of adolescent overweight with special attention to Asian ethnicity, socioeconomic status (SES), and their interaction. Multiple logistic regression models were fitted using a sample of 1533 Asian American adolescents ages 12-17 from the 2007-2012 California Health Interview Survey (CHIS). In addition to Asian ethnicity and socioeconomic status (assessed by family income and parental education level), age, gender, nativity, and two lifestyle variables, fast food consumption and physical activity, were also controlled for in these models. Key predictors of overweight in Asian American adolescents included certain Asian ethnicities (Southeast Asian, Filipino, and mixed ethnicities), low family income (< 300% of the Federal Poverty Level), and being male. Multiplicative interaction terms between low family income and two ethnicities, Southeast Asian and Vietnamese that had the lowest SES among Asian ethnic groups, were significantly associated with greatly elevated odds of being overweight (ORs = 12.90 and 6.67, respectively). These findings suggest that high risk of overweight in Asian American adolescents associated with low family incomes may be further elevated for those in low-income ethnic groups. Future research might investigate ethnic-group SES as a meaningful indicator of community-level socioeconomic disparities that influence the health of Asian Americans. PMID- 27413688 TI - Sedentary behavior among adults: The role of community belonging. AB - Sedentary behavior is a modifiable determinant of health. Little is known about the ways in which contextual factors may influence this behavior. The objectives of this study were to: (1) examine the association between community belonging and adult sedentary behavior during leisure; (2) determine if this association was explained by perceived health. Data were derived from the 2010 Canadian Community Health Survey (N = 11,494 adults). Multinomial regression models and 99% confidence intervals were used to examine associations between sense of community belonging and sedentary behavior, adjusting for sociodemographic variables and perceived health. On average, adults were sedentary for 20-24 h per week during leisure. More than a third of the sample reported low sedentary behavior (<= 19 h a week). In a fully adjusted model participants who were female, in middle adulthood, married, and/or living in higher income households were less sedentary during leisure. Adults with a strong sense of community belonging were also significantly less sedentary during leisure; this association remained significant after adjustment for perceived mental and overall health. Most efforts to address sedentary behavior have focused on individual-level interventions. The present finding highlights the role that larger contextual factors may play in sedentary behavior. Sense of community belonging is a contextual determinant of health that may serve as a useful target for interventions designed to reduce adult sedentary behavior during leisure. PMID- 27413689 TI - Feasibility and effectiveness of a cosmetic intervention program for institutionalized older women in Japan. AB - We examined the feasibility and effectiveness of a cosmetic intervention program for frail older women. Thirty-nine older adults (83.0 +/- 8.65 years) from two nursing homes in Tokyo were allocated to a cosmetic (intervention: n = 27) or a light-exercise (control: n = 12) group according to their nursing home residence. Both groups attended weekly classes over a 5-week period from May to June 2009. The program feasibility was examined using class participation, class attendance, and program adherence rates, while the effectiveness of the program was examined using the Geriatric Depression Scale (GDS) and participants' engagement in positive activities (i.e., engaging in social activities and going outside). The intervention group showed significantly higher rates on all feasibility measures than did the control group (class participation: 24.1% vs. 13.3%, class attendance: 75.5% vs. 32.6%, program adherence: 70.8% vs. 10.0%). Furthermore, the GDS scores decreased significantly in the intervention group, but not the control group. Although the change in GDS score was larger in the intervention group (- 1.30 +/- 2.36) than in the control group (- 0.75 +/- 3.53), the inter group difference in this change was not significant. No significant differences were found between pre- and post-intervention positive activity rates in either group, or in the inter-group comparisons of changes in these rates. Overall, the cosmetic program was highly feasible and effective for improving the mental health of frail older women. However, further studies using longer intervention periods and larger samples would be needed to identify the program effectiveness. PMID- 27413690 TI - Fatal leptospirosis and chikungunya co-infection: Do not forget leptospirosis during chikungunya outbreaks. AB - In endemic areas, leptospirosis can be missed by erroneous clinical or laboratory diagnosis of arboviroses or co-infections with arboviruses and an increase in mortality due to leptospirosis has already been reported during arboviruses outbreaks. During the French Polynesian chikungunya virus outbreak in 2014-2015, two leptospirosis and chikungunya co-infections were reported, one of which was fatal. Diagnosis of leptospiroses was delayed in the context of chikungunya outbreak. In the context of arbovirus outbreak, the risk of misdiagnosis of leptospirosis is maximum and clinicians should initiate early antibiotic therapy if leptospirosis is suspected. A delayed diagnosis of leptospirosis can be responsible for fatal outcome. Leptospirosis should be considered even if dengue or chikungunya virus infections are confirmed by reference molecular testing. PMID- 27413691 TI - Disseminated tuberculosis with prostatic abscesses in an immunocompromised patient-A case report and review of literature. AB - We describe a case of disseminated Mycobacterium tuberculosis (mTB) with prostatic abscess in a newly diagnosed HIV patient in the United States. The patient is a 34 year-old male who presented with respiratory symptoms and was diagnosed with HIV/AIDS complicated by disseminated mTB infection of the lungs, liver, and prostate. His prostate showed abscess formation on imaging that required drainage however he did not present with any genitourinary complaints. Our literature review revealed that prostatic involvement in mTB in the form of granulomatous prostatitis is uncommon; however, abscess formation is extremely rare and only few such cases have been published. Nearly 50% of the patients with prostatic abscess formation present without symptoms and therefore a high level of suspicion should be maintained; imaging should be performed early and prophylactic antibiotics for non-specific urinary symptoms should be avoided as this may lead to drug resistance of mTB to flouroquinolones. PMID- 27413692 TI - Voluminous Incidental Oncocytic Neoplasm of the Adrenal Gland With Uncertain Malignant Potential. AB - A 74-year-old man presented with right flank pain and a palpable mass in the left flank. Blood pressure was normal. Contrastenhanced computed tomography (CT) showed a 17 * 16 * 12 cm retroperitoneal mass over the left kidney, solid and heterogeneous. There were also 3 retro aortic lymph nodes and bilateral renal lithiasis. Twenty four-hour urinary metanephrines and normetanephrines were normal. The patient underwent a resection of the mass with left adrenalectomy by a lumbar incision. Histological findings revealed an adrenal oncocytic neoplasm (AON) with uncertain malignant potential. Six months after surgery, CT control showed neither local nor distant recurrence. PMID- 27413693 TI - Non-Parasitic Chyluria: Our Experience With Sclerotherapy With Solution of Povidone-Iodine and Destrose and A Review of the Literature. AB - Chyluria is the passage of chyle in the urine. The cause seems to be the rupture of retroperitoneal lymphatics into the pyelocaliceal system, giving urine a milky appearance. This condition if left untreated it leads to significant morbidity because of hematochyluria, recurrent renal colic, nutritional problems due to protein losses and immunosuppression resulting from lymphocyturia. We report our experience with the use of povidone iodine with dextrose solution as a sclerosing agent in the management of chyluria in two patients. PMID- 27413696 TI - From the bench to the bedside-promoting the roles of nurses and allied health professionals in the management of lung cancer and mesothelioma. PMID- 27413695 TI - Heart failure in chemotherapy-related cardiomyopathy: Can exercise make a difference? AB - Medical therapies in oncology have resulted in better survival resulting in a large population who are at risk of early and late cardiac complications of chemotherapy. Cardiotoxicity related to chemotherapy can manifest decades after treatment with a threefold higher mortality rate as compared to idiopathic dilated cardiomyopathy. The leading cause of death in cancer survivors seems to be cardiac. Early detection and intervention could prevent progression of heart failure to end stage disease requiring advanced therapies such as implantation of ventricular assist devices or cardiac transplantation. This review focuses on the role of exercise in cardioprotection in this population. The current practice of depending on ejection fraction for diagnosis of heart failure is suboptimal to detect subclinical disease. It is also important to diagnose and treat early diastolic dysfunction as this tends to lead to heart failure with preserved ejection fraction. Hence we suggest an algorithm here that is based on using strain rate and tissue Doppler imaging modalities to detect subclinical systolic and diastolic dysfunction. Further research is warranted in terms of defining exercise prescriptions in this population. Human studies with multicenter participation in randomized controlled trials should be done to elucidate the intricacies of aerobic exercise intervention in cardiotoxicity dependent heart failure. It is also necessary to assess the utility of exercise interventions in the different chemotherapeutic regimens as they impact the outcomes. PMID- 27413694 TI - Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma. AB - Senile cataract is a clouding of the lens in the aging eye leading to a decrease in vision. Symptoms may include faded colors, blurry vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Cataracts are the cause of half of blindness and 33% of visual impairment worldwide. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cells plasma membrane damage which causes clouding of the lens, light scattering, and obstruction of vision. ROS induced damage in the lens cell may consist of oxidation of proteins, DNA damage and/or lipid peroxidation, all of which have been implicated in cataractogenesis. The inner eye pressure (also called intraocular pressure or IOP) rises because the correct amount of fluid can't drain out of the eye. With primary open-angle glaucoma, the entrances to the drainage canals are clear and should be working correctly. The clogging problem occurs further inside the drainage canals, similar to a clogged pipe below the drain in a sink. The excessive oxidative damage is a major factor of the ocular diseases because the mitochondrial respiratory chain in mitochondria of the vital cells is a significant source of the damaging reactive oxygen species superoxide and hydrogen peroxide. However, despite the clinical importance of mitochondrial oxidative damage, antioxidants have been of limited therapeutic success. This may be because the antioxidants are not selectively taken up by mitochondria, but instead are dispersed throughout the body, ocular tissues and fluids' moieties. This work is an attempt to integrate how mitochondrial reactive oxygen species (ROS) are altered in the aging eye, along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. The authors developed and patented the new ophthalmic compositions including N-acetylcarnosine acting as a prodrug of naturally targeted to mitochondria l-carnosine endowed with pluripotent antioxidant activities, combined with mitochondria-targeted rechargeable antioxidant (either MitoVit E, Mito Q or SkQs) as a potent medicine to treat ocular diseases. Such specificity is explained by the fact that developed compositions might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo and outside mitochondria in the cellular and tissue structures of the lens and eye compartments. Mitochondrial targeting of compounds with universal types of antioxidant activity represents a promising approach for treating a number of ROS-related ocular diseases of the aging eye and can be implicated in the management of cataracts and primary open-angle glaucoma. PMID- 27413697 TI - Approach to offering remote support to mesothelioma patients: the mesothelioma survivor project. AB - BACKGROUND: From the moment of diagnosis, malignant mesothelioma (MM) decreases health-related quality of life (QOL) in patients and their caregivers. In addition to symptoms of disease, aggressive treatments such as surgery, radiation, and chemotherapy can cause extreme side effects-chemotherapy specifically is associated with chronic fatigue, unremitting nausea, vomiting, and systemic pain. These side effects of treatments can be burdensome enough to lead to noncompliance or outright refusal of continuation of care. METHODS: The platform for the support group was remote, consisting of online and telephone domains. Participants would utilize both online and phone systems during sessions held once a week for a total of six weeks. Sessions were guided and kept closed, available only to those affected by mesothelioma. Follow-up information and session summaries were provided online after support meetings. RESULTS: Using a 0 5 Likert Scale, consistent attendees reported support groups as very helpful. Irregular attendees had mixed feelings ranging from extremely helpful to neutral. Eighty per cent of attendees participated in support groups prior to this project. CONCLUSIONS: Active participation in a guided and closed support group allowed participants to share their experiences and concerns about their diagnoses comfortably, supporting transition beyond active-treatment. Online space gave participants a place to provide more reflective responses outside the main dialogue of support sessions. PMID- 27413699 TI - The lung cancer nurse role in the management of paraneoplastic syndromes in lung cancer. AB - Paraneoplastic syndromes (PNS) associated with lung cancer are well recognised, are often complex to diagnose, and have minimal evidence to promote nursing and medical management. This paper aims to help guide lung cancer nurses to identify the most common and rarer PNS together with basic clinical management advice to help develop nursing assessments and interventions. The issues regarding the pathway of care at diagnosis together with palliative and supportive care requirements will be addressed and will aim to promote best practice in patients diagnosed with PNS and lung cancer. PMID- 27413698 TI - Ethical challenges in conducting clinical research in lung cancer. AB - The article examines ethical challenges that arise with clinical lung cancer research focusing on design, recruitment, conduct and dissemination. DESIGN: problems related to equipoise can arise in lung cancer studies. Equipoise is an ethics precondition for RCTs and exists where there is insufficient evidence to decide which of two or more treatments is best. Difficulties arise in deciding what level of uncertainty constitutes equipoise and who should be in equipoise, for example, patients might not be even where clinicians are. Patient and public involvement (PPI) can reduce but not remove the problems. Recruitment: (I) lung cancer studies can be complex, making it difficult to obtain good quality consent. Some techniques can help, such as continuous consent. But researchers should not expect consent to be the sole protection for participants' welfare. This protection is primarily done elsewhere in the research process, for example, in ethics review; (II) the problem of desperate volunteers: some patients only consent to a trial because it gives them a 50/50 option of the treatment they want and can be disappointed or upset if randomised to the other arm. This is not necessarily unfair, given clinical equipoise. However, it should be avoided where possible, for example, by using alternative trial designs; (III) the so-called problem of therapeutic misconception: this is the idea that patients are mistaken if they enter trials believing this to be in their clinical best interest. We argue the problem is misconceived and relates only to certain health systems. Conduct: lung cancer trials face standard ethical challenges with regard to trial conduct. PPI could be used in decisions about criteria for stopping rules. DISSEMINATION: as in other trial areas, it is important that all results, including negative ones, are reported. We argue also that the role of PPI with regard to dissemination is currently under-developed. PMID- 27413700 TI - The importance of exercise in lung cancer treatment. AB - There is emerging evidence that exercise can help in a variety of different ways for people with lung cancer. Exercise can be beneficial at any stage of the patient journey through increasing strength, endurance and decreasing emotional issues. A recovery fitness program is described and provides guidance on breathing, stretching, aerobic exercise and strength training. There are more people surviving lung cancer with services needing to cater for the varying requirements of each patient. Promoting physical activity is an important facet of health care management and collaboration between providers of services is required. PMID- 27413701 TI - Overcoming toxicity-challenges in chemoradiation for non-small cell lung cancer. AB - Concurrent chemoradiation (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (NSCLC) with a modest survival benefit over sequential chemoradiation or radiotherapy (SCRT) alone. However, this benefit is at the cost of increasing acute toxicity such as esophagitis. Previous analysis revealed several predictive parameters in dose-volume and patient characteristics which helped us to identify those patients at risk for severe esophagus toxicity. As a result, supportive care interventions including individualized patient information, dietary guidance, adequate medication, hydration and tubefeeding could be initiated. This paper discusses the challenges in overcoming chemoradiation induced acute esophageal toxicity (AET). PMID- 27413702 TI - The role of the occupational therapist in the care of people living with lung cancer. AB - This paper aims to explore the vital role occupational therapists play in enabling people living with lung cancer to continue to actively live. Core assessments and interventions employed by occupational therapists are described in a case study. It will demonstrate how people living with lung cancer can continue to participate in meaningful and chosen life roles, even in the face of functional decline. Skilled management by the occupational therapist of the refractory symptoms of advanced lung cancer supports this participation. PMID- 27413703 TI - Pros: should a patient with stage IA non-small cell lung cancer undergo invasive mediastinal staging? PMID- 27413704 TI - Cons: should a patient with stage IA non-small cell lung cancer undergo invasive mediastinal staging? PMID- 27413705 TI - Rebuttal from Dr. Obiols and Dr. Call. PMID- 27413706 TI - Rebuttal from Dr. Decaluwe and Dr. Dooms. PMID- 27413707 TI - Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: a systematic review with meta-analysis. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. METHODS: We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias. RESULTS: Five studies published between 2010 and 2014 were eligible for this systematic review with meta-analysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports. CONCLUSIONS: LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC. PMID- 27413708 TI - Assessing the shift of radiobiological metrics in lung radiotherapy plans using 2D gamma index. AB - BACKGROUND: The purpose of this work is to investigate the 2D gamma (gamma) maps to illustrate the change of radiobiological outcomes for lung radiotherapy plans and evaluate the correlation between tumor control probability (TCP), normal tissue complication probability (NTCP) with gamma passing rates (gamma-rates). METHODS: Nine patients with lung cancer were used. The doses were calculated using Modified Batho method integrated with pencil beam convolution (MB-PBC) and anisotropic analytical algorithm (AAA) using the same beam arrangements and prescription dose. The TCP and NTCP were estimated, respectively, using equivalent uniform dose (EUD) model and Lyman-Kutcher-Burman (LKB) model. The correlation between DeltaTCP or DeltaNTCP with gamma-rates, from 2%/2 and 3%/3 mm, were tested to explore the best correlation predicting the relevant gamma criteria using Spearman's rank test (rho). Wilcoxon paired test was used to calculate P value. RESULTS: TCP value was significantly lower in the recalculated AAA plans as compared to MB plans. However, AAA predicted more NTCP on lung pneumonitis according to the LKB model and using relevant radiobiological parameters (n, m and TD50) for MB-PBC and AAA, with P=0.03. The data showed a weak correlation between radiobiological metrics with gamma-rates or gamma-mean, rho<0.3. CONCLUSIONS: AAA and MB yield different TCP values as well as NTCP for lung pneumonitis based on the LKB model parameters. Therefore, 2D gamma-maps, generated with 2%/2 or 3%/3 mm, could illustrate visual information about the radiobiological changes. The information is useful to evaluate the clinical outcome of a radiotherapy treatment and to approve the treatment plan of the patient if the dose constraints are respected. On the other hand, the gamma-maps tool can be used as quality assurance (QA) process to check the predicted TCP and NTCP from radiobiological models. PMID- 27413709 TI - Lung cancer stem cells-characteristics, phenotype. AB - Lung cancer remains a major cause of cancer-related deaths worldwide with unfavourable prognosis mainly due to the late stage of disease at presentation. High incidence and disease recurrence rates are a fact despite advances in treatment. Ongoing experimental and clinical observations suggest that the malignant phenotype in lung cancer is sustained by lung cancer stem cells (CSCs) which are putative stem cells situated throughout the airways that have the potential of initiating lung cancer formation. These cells share the common characteristic of increased proliferation and differentiation, long life span and resistance to chemotherapy and radiation therapy. This review summarises the current knowledge on their characteristics and phenotype. PMID- 27413710 TI - Anticoagulation, ferrotoxicity and the future of translational lung cancer research. AB - Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms. PMID- 27413711 TI - Non-small cell lung cancer: current treatment and future advances. AB - Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID- 27413712 TI - Tackling ALK in non-small cell lung cancer: the role of novel inhibitors. AB - Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy. Unfortunately, virtually all ALK-rearranged tumors acquire resistance to crizotinib, frequently within one year since the treatment initiation. To date, therapeutic strategies to overcome crizotinib resistance have focused on the use of more potent and structurally different compounds. Second-generation ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802/RO5424802) and brigatinib (AP26113) have shown relevant clinical activity, consequently fostering their rapid clinical development and their approval by health agencies. The third-generation inhibitor lorlatinib (PF-06463922), selectively active against ALK and ROS1, harbors impressive biological potency; its efficacy in reversing resistance to crizotinib and to other ALK inhibitors is being proven by early clinical trials. The NTRK1-3 and ROS1 inhibitor entrectinib (RXDX-101) has been reported to act against NSCLC harboring ALK fusion proteins too. Despite the quick development of these novel agents, several issues remain to be discussed in the treatment of patients suffering from ALK-rearranged NSCLC. This position paper will discuss the development, the current evidence and approvals, as long as the future perspectives of new ALK inhibitors beyond crizotinib. Clinical behaviors of ALK-rearranged NSCLC vary significantly among patients and differential molecular events responsible of crizotinib resistance account for the most important quote of this heterogeneity. The precious availability of a wide range of active anti-ALK compounds should be approached in a critical and careful perspective, in order to develop treatment strategies tailored on the disease evolution of every single patient. PMID- 27413713 TI - A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer. AB - Alteration in the expression of microRNAs (miRNAs) is associated with oncogenesis and cancer progression. In this review we aim to suggest that elevated levels of estrogens and their metabolites inside the lungs as a result of cigarette smoke exposure can cause widespread repression of miRNA and contribute to lung tumor development. Anti-estrogenic compounds, such as the components of cruciferous vegetables, can attenuate this effect and potentially reduce the risk of lung cancer (LC) among smokers. PMID- 27413714 TI - Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements. AB - The most frequent epidermal growth factor receptor (EGFR) mutations found by traditional or comprehensive molecular profiling of lung adenocarcinomas include indels of exon 19 (the exon 19 deletion delE746_A750 being the most common) and the exon 21 L858R point mutation. The current approval labels for first line palliative gefitinib 250 mg/day, erlotinib 150 mg/day and afatinib 40 mg/day for advanced lung cancers require the presence of the aforementioned classical/sensitizing EGFR mutations. Other gefitinib, erlotinib and afatinib sensitizing mutations include exon 18 indels, G719X, exon 19 insertions, A763_Y764insFQEA, S768I and L861Q; for which off-label EGFR kinase inhibitor use is generally agreed upon by thoracic oncologists. The main biological mechanism of resistance to approved first line EGFR inhibitors is the selection/acquisition of EGFR-T790M that in itself can be inhibited by osimertinib 80 mg/day, a 3(rd) generation EGFR inhibitor that is bypassed by EGFR-C797X mutations. Another class of de novo inhibitor insensitive mutation includes EGFR exon 20 insertions. More recently, the dichotomy of only point mutations or indels explaining aberrant kinase activation of EGFR plus inhibitor response has been shattered by the discovery of uncommon (<0.5% of all EGFR mutations) genomic events involving exon 18-25 kinase domain duplications (KDD) and rearrangements (EGFR-RAD51 or EGFR PURB). The latter lead to oncogene addiction, enhanced sensitivity to kinase inhibitors in vitro and clinical responses to approved EGFR inhibitors. The enhanced landscape of EGFR inhibitor-responsive genotypes highlights that comprehensive molecular profiling may be necessary to maximize the identification of all cases that can benefit from precision oncology. PMID- 27413715 TI - Further results of the FRAGMATIC trial of thromboprophylaxis in lung cancer. PMID- 27413716 TI - Primitive neuroectodermal tumor of lungs in adults: a rare series of three cases treated with upfront chemo-radiation. AB - Primitive neuroectodermal tumors (PNETs) are highly malignant small round blue cell tumors of neuroectodermal origin belonging to either central nervous system, autonomic nervous system or peripheral Askin's or Ewing's group of neoplasms. The latter generally arise in soft tissues of trunk or axial skeleton in children and early adolescents. However in adults this entity is very uncommon. Of all peripheral entities, primary PNET of lungs without chest wall or pleural involvement in adults are extremely rare and have been scarcely reported in world literature as single case reports. We hereby report a series of three interesting cases of adult PNET of lung diagnosed and treated in our institute. The chief presenting complaints of these patients were of chest pain, cough and dyspnea. The cases were diagnosed on the basis of imaging and biopsy which confirmed these lesions to be of PNET histology, confirmed by immunopositivity for neuron specific enolase (NSE), synaptophysin, chromogranin, CD 99 and vimentin on immunohistochemistry (IHC). All three were deemed unresectable in view of infiltration of nearby vital organs and high chances of morbidity. They were treated with upfront chemotherapy followed by conformal radiotherapy (RT) to the residual disease to which they showed significant response both clinically and radiologically. Presently these patients are on regular follow-up for over 6 months without any evidence of progression of disease or distant metastasis. PMID- 27413717 TI - Recurrent "pneumonia" in left lower lobe lasting for 8 years: a case report. AB - Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC. PMID- 27413718 TI - Scrub typhus masquerading as HELLP syndrome and puerperal sepsis in an asymptomatic malaria patient. AB - Scrub typhus and malaria can involve multiple organ systems and are notoriously known for varied presentations. However, clinical malaria or scrub typhus is unusual without fever. On the other hand, altered sensorium with or without fever, dehydration, hemorrhage and hemolysis may lead to low blood pressure. Presence of toxic granules and elevated band forms in such patients can even mimic sepsis. When such a patient is in the peripartum period, it creates a strong clinical dilemma for the physician especially in unbooked obstetric cases. We present such a case where a 26-year-old unbooked female presented on second postpartum day with severe anemia, altered sensorium, difficulty in breathing along with jaundice and gum bleeding without history of fever. Rapid diagnostic test for malaria was negative and no eschar was seen. These parameters suggested a diagnosis of HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet) syndrome with or without puerperal sepsis. Subsequently she was diagnosed as having asymptomatic malaria and scrub typhus and responded to the treatment of it. The biochemical changes suggestive of HELLP syndrome also subsided. We present this case to emphasize the fact that mere absence of fever and eschar does not rule out scrub typhus. It should also be considered as a differential diagnosis in patients with symptoms and signs suggesting HELLP syndrome. Asymptomatic malaria can complicate case scenario towards puerperal sepsis by giving false toxic granules and band form in such situations. PMID- 27413719 TI - Misoprostol use in medical evacuation of spontaneous miscarriage: Pilot drug use evaluation study at the Women's Hospital in Qatar. AB - BACKGROUND: Misoprostol is a synthetic prostaglandin E1 that induces cervical effacement and uterine contractions at all gestational ages, thus facilitating uterine evacuation and pregnancy termination. Successful medical evacuation of spontaneous miscarriage with minimal adverse effects can be performed using misoprostol-only regimen if given as indicated and if the administered dose, frequency of the dosage, and number of total doses are appropriate. AIM: To conduct a drug use evaluation by investigating indications, appropriateness of dosing, and clinical outcome of misoprostol-only regimen when used for medical evacuation of spontaneous miscarriage at the Women's Hospital in Doha, Qatar. MATERIALS AND METHODS: A retrospective descriptive drug use evaluation was conducted on women with spontaneous miscarriage who received misoprostol for medical evacuation during August 2013. The current practice at the Women's Hospital was compared with the recommendation from the World Health Organization (WHO). Patients were stratified into three groups based on weeks of amenorrhea. RESULTS: A total of 107 patients received misoprostol during August 2013, of which 33 (31%) were included in the study. In these patients, the main indication for misoprostol use was missed miscarriage (54.5%). In the group of patients at <= 9 weeks of gestation, 80% received an initial dose of 800 MUg, 80% received frequency within the WHO recommendation, and the majority had surgical evacuation (80%). In the group of patients at 10-12 weeks of gestation, more than 80% received an initial dose of 800 MUg, 6% received frequency within the WHO recommendation, and more than 75% had successful medical evacuation. In the group of patients at 13-22 weeks of gestation, more than 80% received an initial dose of 400 MUg, more than 80% received frequency within the WHO recommendation, and 54% had successful medical evacuation. Overall, more than 70% of the patients received <= 3 total doses of misoprostol and more than 60% had successful medical evacuation as a clinical outcome. CONCLUSIONS: Despite the current practice at the Women's Hospital not always being in accordance with the WHO recommendation, successful medical evacuation was achieved in most patients. PMID- 27413720 TI - Prediction of cardiovascular disease from the early stages of life: A forgotten issue? PMID- 27413721 TI - Letter to the Editor. PMID- 27413722 TI - Letter to the Editor. AB - In reviewing Melikyan et al., we discuss what we think are weaknesses in the case report. The authors did not report on known risk factors for cerebrovascular accident and vertebral artery dissection. Known symptoms that appear early in vertebral artery dissection were not reported or denied, specifically related to changes in the patient's pattern of neck pain. Causality was assumed when only a weak temporal relation was involved. Finally, the case report makes it appear that the manipulation was performed by someone other than a chiropractor but therefore erroneously uses chiropractic in the title. PMID- 27413723 TI - Viral Hepatitis and Its Complications. PMID- 27413724 TI - Liver Failure due to Acute Viral Hepatitis (A-E). AB - BACKGROUND: Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. METHODS: A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. RESULTS: Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. CONCLUSION: Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF. PMID- 27413725 TI - Management of HBV and HBV/HDV-Associated Liver Cirrhosis. AB - BACKGROUND: Chronic hepatitis B virus (HBV) infection and hepatitis delta virus (HDV) co-infection lead to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). METHODS: We review the current knowledge of the management of HBV mono-infection and HBV/HDV co-infection with a special emphasis on liver cirrhosis. RESULTS: Treatment options for chronic hepatitis B are pegylated interferon (PEG-IFN) alfa and nucleos(t)ide analogues (NUC). PEG-IFN is a finite option to achieve hepatitis B surface antigen loss in compensated cirrhosis. However, this goal is rare. NUC are potent to achieve HBV DNA suppression but long-term treatment is mandatory in most cases. Long-term treatment with NUC can lead to reversion of liver cirrhosis, improve liver function, prevent liver transplantation, and reduces but does not eliminate the risk for development of HCC. Treatment options for hepatitis D are limited to PEG IFN. Although late relapse is common, treatment with PEG-IFN reduces disease progression. However, new treatments are urgently needed for HDV infection. CONCLUSION: Early treatment of chronic hepatitis B and D is important to prevent complications of cirrhosis. HCC surveillance remains important in patients with cirrhosis. PMID- 27413726 TI - Management of HCV-Associated Liver Cirrhosis. AB - BACKGROUND: Treatment of chronic hepatitis C infection is most urgent in patients with severe liver fibrosis and cirrhosis because of the high risk of decompensation, hepatocellular carcinoma, and consecutively death. The development and approval of several direct-acting antiviral drugs (DAA) in the past years has revolutionized antiviral therapy especially for patients with liver cirrhosis. METHODS: This review will focus on recent data from clinical trials and recommendations for the therapy of hepatitis C-infected patients with compensated cirrhosis. RESULTS: Clinical data for cirrhotic patients mainly exist for a combination of the nucleotide analog sofosbuvir with either a protease inhibitor (simeprevir) or an NS5A inhibitor (daclatasvir, ledipasvir) or a three DAA combination consisting of an NS3 protease inhibitor, an NS5A inhibitor, and a non-nucleoside NS5B inhibitor (paritaprevir/ritonavir, ombitasvir, and dasabuvir). Rates of sustained virologic response in patients with compensated cirrhosis are comparable to patients without cirrhosis; however, the addition of ribavirin and/or longer treatment durations are especially recommended when other negative predictors are present, such as prior treatment failure, features of advanced cirrhosis, or the presence of baseline resistance. CONCLUSION: Nowadays, a highly active, short, and safe interferon-free treatment regimen is available for almost all patients. PMID- 27413727 TI - Pre- and Post-Transplant Antiviral Therapy (HBV, HCV). AB - BACKGROUND: Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated liver cirrhosis is a major indication for liver transplantation. This concise review gives an overview about current interferon (IFN)-free treatment options before and after liver transplantation in HBV- or HCV-associated liver disease. METHODS: A PubMed database search using the terms hepatitis B, hepatitis C, cirrhosis, and liver transplantation was performed to identify significant clinical studies as well as national and international guidelines. RESULTS: Studies investigating IFN free treatment in patients with decompensated HBV as well as in HCV-associated cirrhosis are scarce. Hepatic recompensation during antiviral therapy seems more frequent in patients with HBV than in those with HCV-associated cirrhosis. Graft hepatitis B or C is characterized by an accelerated and unfavorable course. Graft infection prophylaxis is safe and efficacious in HBV-related liver transplantation. Eradication of HCV prior to liver transplantation prevents HCV graft infection, and IFN-free treatment of established HCV graft infection is safe and associated with high sustained virologic response rates. CONCLUSION: Patients with HBV-associated cirrhosis should be treated prior to liver transplantation, and receive a continuing graft infection prophylaxis thereafter. Patients with HCV-associated decompensated cirrhosis may be considered as candidates for antiviral therapy prior to liver transplantation or may be treated subsequently. PMID- 27413728 TI - Surveillance of Hepatocellular Carcinoma and Diagnostic Algorithms in Patients with Liver Cirrhosis. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the most deadly complication of all major chronic liver diseases. Since early detection is the most significant determinant of overall survival, intense screening is of major importance. METHODS: This overview is based on a systematic review of the available literature on HCC screening and surveillance in the PubMed database. RESULTS: Over the last decades, major etiological risk factors were identified and the population at highest risk for the development of HCC was clearly defined. Screening in these patients has been repeatedly demonstrated to detect early tumor stages and to be cost-effective. Therefore, screening is recommended by all current guidelines and usually comprises a bi-annual ultrasound examination in Western countries. In some Asian countries biomarkers are also used; however, their efficiency for Western HCCs remains to be determined. The detection of lesions >1 cm during routine screening requires subsequent confirmation of HCC. The diagnosis can be accurately established by modern imaging techniques, i.e. computed tomography or magnetic resonance imaging, in the majority of patients. In ambiguous cases and if radiological criteria are not met by two imaging techniques, biopsies remain the gold standard for diagnosis. Furthermore, histology is of key importance for the development of new diagnostic and predictive biomarkers. CONCLUSION: Screening and detection algorithms for patients at risk for HCC are effective and should be rigorously implemented in clinical routine. PMID- 27413729 TI - Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. METHODS: A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. RESULTS: The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. CONCLUSION: Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment. PMID- 27413730 TI - Antiviral Therapy in Patients with Viral Hepatitis and Hepatocellular Carcinoma: Indications and Prognosis. AB - BACKGROUND: Chronic hepatitis B and C infections represent major risk factors for the development of hepatocellular carcinoma (HCC). Recently, the management of patients with viral hepatitis has dramatically changed. In the present review we discuss the impact of these developments on the prevention of HCC as well as the treatment of patients with HCC. METHODS: Studies indexed in Medline between 1990 and 2015 (November) were reviewed. The terms 'hepatocellular carcinoma', 'HCC', 'hepatitis B', 'hepatitis C', 'viral hepatitis', and combinations of these terms were used. RESULTS: Patients with chronic hepatitis B or hepatitis C without HCC should be evaluated for antiviral therapy, since antiviral therapy was suggested to reduce the risk of HCC development. Cirrhotic patients infected with hepatitis B virus (HBV) require antiviral therapy, while cirrhotics infected with hepatitis C virus (HCV) need to be prioritized for therapy with interferon (IFN)-free regimens. Antiviral therapy should be considered in HBV-infected patients with HCC, especially to prevent tumor recurrence after curative-intended therapy or to prevent hepatic decompensation. HCV-infected patients with HCC should be considered in similar intention for IFN-free antiviral therapy, depending on the tumor stage and life expectancy. CONCLUSION: Patients with viral hepatitis should be considered for antiviral treatment for the prevention of HCC development as well as during HCC treatment. PMID- 27413731 TI - Incidence of Metachronous Distant Metastasis and ypN Classification Influence Patient Survival in Endosonographically Confirmed uT3 Rectal Cancer after Neoadjuvant Therapy and R0 Resection: A Historical Cohort Analysis. AB - BACKGROUND: Tumor response after neoadjuvant radiochemotherapy (NRC) prior to surgery and other parameters are likely to have an influence on the survival rate of patients suffering from T3 rectal cancer. METHODS: 51 patients (17 female, 34 male; 59.0 years; Apache < 9 points: 95.1%; ASA I-II 88.3% and ASA III 11.8%) were treated with NRC (50.4 Gy; 5-fluorouracil/folinic acid) 4-6 weeks prior to surgery because of uT3 rectal cancer (G2: 96%; adenocarcinoma 86.3%; cUICC II 62.7%). NRC led to a tumor response (TR) (ypT0-ypT2) in 45.1% (ypT0N0M0 7.8%). RESULTS: Neither the age of patients nor Apache/ASA score, histology, UICC staging, ypTNM, Dukes staging, infiltration of vessels, surgical procedure, local recurrence nor TR had a significant influence on the patients' survival time. Patients with metachronous distant metastasis (MDM) during the follow-up period (mean: 8.2 years; 1 month to 14.5 years) and patients with ypN1-ypN2 had a significantly shorter survival time. CONCLUSIONS: NRC prior to surgery leads to a remarkable TR rate but has no significant impact of TR on the patients' survival time. Occurrence of MDM during the follow-up period and ypN1/N2 status do have a greater influence. It is necessary to investigate larger cohorts of patients in the future to obtain more conclusive results and to define factors with influence on survival. PMID- 27413732 TI - Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy. AB - Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n = 42) and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP) (n = 20), acquired inflammatory demyelinating neuropathy (AIDP) (n = 13), Charcot Marie Tooth (CMT) type 1 or 4C (n = 15), carpal tunnel syndrome (CTS) (n = 11), and amyotrophic lateral sclerosis (ALS) (n = 18). Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA) and CIDP (median nerve: 38.9 mA), whereas values similar to normal controls (median nerve: 25.3 mA) were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier. PMID- 27413733 TI - Isolation and Identification of the Antimicrobial Agent Beauvericin from the Endophytic Fusarium oxysporum 5-19 with NMR and ESI-MS/MS. AB - Endophytic microbe has been proved to be one of rich sources of bioactive natural products with potential application for new drug and pesticide discovery. One cyclodepsipeptide, beauvericin, was firstly isolated from the fermentation broth of Fusarium oxysporum 5-19 endophytic on Edgeworthia chrysantha Linn. Its chemical structure was unambiguously identified by a combination of spectroscopic methods, such as HRESI-MS and (1)H and (13)C NMR. ESI-MS/MS was successfully used to elucidate the splitting decomposition route of the positive molecule ion of beauvericin. Antimicrobial results showed that this cyclodepsipeptide had inhibitory effect on three human pathogenic microbes, Candida albicans, Escherichia coli, and Staphylococcus aureus. In particular, beauvericin exhibited the strongest antimicrobial activity against S. aureus with MIC values of 3.91 MUM, which had similar effect with that of the positive control amoxicillin. PMID- 27413736 TI - Myocardial Diseases: Current Views on Etiopathogenesis, Diagnostic Modalities, and Therapeutic Options. PMID- 27413735 TI - The Effect of Adipose-Derived Stem Cells on Full-Thickness Skin Grafts. AB - Background. The purpose of this study was to evaluate the effects of ASCs on full thickness skin grafts. Specifically, we investigated the anti-inflammatory effects of ASCs that are mediated via regulation of the phenotypes of activated macrophages. Methods. ASCs were isolated, cultured, and injected under full thickness skin grafts in 15 rats (ASC group). An additional 15 rats served as controls (PBS group). Skin graft survival assessment and vascularization detection were assessed with H&E staining and laser Doppler blood flowmetry (LDF). The effects of ASCs on angiogenesis, anti-inflammation, collagen accumulation-promoting, and antiscarring were assessed. Results. We found that the skin graft survival rate was significantly increased in the ASC group. The neovascularization, collagen deposition, collagen type I to type III ratio, and levels of VEGF and TGF-beta3 in the ASC group were markedly higher than those in the PBS group at day 14. Additionally, in the ASC group, the levels of iNOS, IL 1beta, and TNF-alpha were remarkably decreased, whereas the levels of IL-10 and Arg-1 were substantially increased. Conclusions. Our results confirm that ASCs transplantation can effectively improve full-thickness skin graft survival. Additionally, the anti-inflammatory role of ASCs may indirectly contribute to skin graft survival via its effect on macrophage polarization. PMID- 27413734 TI - Manipulation of DNA Repair Proficiency in Mouse Models of Colorectal Cancer. AB - Technical and biological innovations have enabled the development of more sophisticated and focused murine models that increasingly recapitulate the complex pathologies of human diseases, in particular cancer. Mouse models provide excellent in vivo systems for deciphering the intricacies of cancer biology within the context of precise experimental settings. They present biologically relevant, adaptable platforms that are amenable to continual improvement and refinement. We discuss how recent advances in our understanding of tumorigenesis and the underlying deficiencies of DNA repair mechanisms that drive it have been informed by using genetically engineered mice to create defined, well characterized models of human colorectal cancer. In particular, we focus on how mechanisms of DNA repair can be manipulated precisely to create in vivo models whereby the underlying processes of tumorigenesis are accelerated or attenuated, dependent on the composite alleles carried by the mouse model. Such models have evolved to the stage where they now reflect the initiation and progression of sporadic cancers. The review is focused on mouse models of colorectal cancer and how insights from these models have been instrumental in shaping our understanding of the processes and potential therapies for this disease. PMID- 27413737 TI - Effects of Shaoyao-Gancao Decoction on Infarcted Cerebral Cortical Neurons: Suppression of the Inflammatory Response following Cerebral Ischemia-Reperfusion in a Rat Model. AB - The mechanisms by which Shaoyao-Gancao decoction (SGD) inhibits the production of inflammatory cytokines in serum and brain tissue after cerebral ischemia reperfusion (CI-RP) in rats were investigated. A right middle cerebral artery occlusion was used to induce CI-RP after which the rats were divided into model (n = 39), SGD (n = 28), clopidogrel (n = 25) and sham operated (n = 34) groups. The Bederson scale was used to evaluate changes in behavioral indices. The levels of IL-1beta, TNF-alpha, MCP-1, IL-10, RANTES, VEGF, and TGF-beta1 in the serum and infarcted brain tissues were measured. Nissl body and immunohistochemical staining methods were used to detect biochemical changes in neurons, microglial cells, and astrocytes. Serum levels of VEGF, TNF-alpha, MCP-1, IL-1beta, and IL 10 increased significantly 24 h after CI-RP. In brain tissue, levels of TNF-alpha and IL-1beta significantly increased 24 h after CI-RP, whereas levels of TGF beta1 and MCP-1 were significantly higher 96 h after CI-RP (P < 0.05). SGD or clopidogrel after CI-RP reduced TNF-alpha and IL-1beta levels in brain tissue and serum levels of MCP-1, IL-1beta, and IL-10. SGD increased the number of NeuN positive cells in infarcted brain tissue and reduced the number of IBA1-positive and GFAP-positive cells. The efficacy of SGD was significantly higher than that of clopidogrel. PMID- 27413738 TI - Diagnosis of Xeroderma Pigmentosum Groups A and C by Detection of Two Prevalent Mutations in West Algerian Population: A Rapid Genotyping Tool for the Frequent XPC Mutation c.1643_1644delTG. AB - Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder. Considering that XP patients have a defect of the nucleotide excision repair (NER) pathway which enables them to repair DNA damage caused by UV light, they have an increased risk of developing skin and eyes cancers. In the present study, we investigated the involvement of the prevalent XPA and XPC genes mutations nonsense mutation (c.682C>T, p.Arg228X) and a two-base-pair (2 bp) deletion (c.1643_1644delTG or p.Val548Ala fsX25), respectively-in 19 index cases from 19 unrelated families in the West of Algeria. For the genetic diagnosis of XPA gene, we proceeded to PCR-RFLP. For the XPC gene, we validated a routine analysis which includes a specific amplification of a short region surrounding the 2 bp deletion using a fluorescent primer and fragment sizing (GeneScan size) on a sequencing gel. Among the 19 index cases, there were 17 homozygous patients for the 2 bp deletion in the XPC gene and 2 homozygous patients carrying the nonsense XPA mutation. Finally, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. The use of fragment sizing is the simplest method to analyze this 2 bp deletion for the DNA samples coming from countries where the mutation c.1643_1644delTG of XPC gene is prevalent. PMID- 27413739 TI - Preventive Effects of Houttuynia cordata Extract for Oral Infectious Diseases. AB - Houttuynia cordata (HC) (Saururaceae) has been used internally and externally as a traditional medicine and as an herbal tea for healthcare in Japan. Our recent survey showed that HC poultice (HCP) prepared from smothering fresh leaves of HC had been frequently used for the treatment of purulent skin diseases with high effectiveness. Our experimental study also demonstrated that ethanol extract of HCP (eHCP) has antibacterial, antibiofilm, and anti-inflammatory effects against S. aureus which caused purulent skin diseases. In this study, we focused on novel effects of HCP against oral infectious diseases, such as periodontal disease and dental caries. We determined the antimicrobial and antibiofilm effects of water solution of HCP ethanol extract (wHCP) against important oral pathogens and investigated its cytotoxicity and anti-inflammatory effects on human oral epithelial cells. wHCP had moderate antimicrobial effects against some oral microorganisms and profound antibiofilm effects against Fusobacterium nucleatum, Streptococcus mutans, and Candida albicans. In addition, wHCP had no cytotoxic effects and could inhibit interleukin-8 and CCL20 productions by Porphyromonas gingivalis lipopolysaccharide-stimulated human oral keratinocytes. Our findings suggested that wHCP may be clinically useful for preventing oral infectious diseases as a mouthwash for oral care. PMID- 27413740 TI - The Relationship of Oxidation Sensitivity of Red Blood Cells and Carbonic Anhydrase Activity in Stored Human Blood: Effect of Certain Phenolic Compounds. AB - It has been reported that many modifications occur with the increase of oxidative stress during storage in erythrocytes. In order to delay these negative changes, we evaluated whether the addition of substances likely to protect antioxidant capacity in stored blood would be useful. Therefore, we investigated the effects of resveratrol, tannic acid, and caffeic acid in lipid peroxidation and antioxidant capacity of erythrocytes in stored blood. Donated blood was taken into four CPD containing blood bags. One bag was used as the control, and the others were supplemented with caffeic acid (30 MUg/mL), resveratrol (30 MUg/mL), and tannic acid (15 MUg/mL), respectively. Erythrocyte lipid peroxidation, sensitivity to oxidation, glutathione levels and carbonic anhydrase, glutathione peroxidase, and catalase activities were measured on days 0, 7, 14, 21, and 28. In the control group, erythrocyte malondialdehyde levels and sensitivity to oxidation were increased whereas glutathione, glutathione peroxidase, and catalase levels were decreased (p < 0.05). Resveratrol and caffeic acid prevented malondialdehyde accumulation and preserved glutathione, glutathione peroxidase, and catalase activities in erythrocytes. We demonstrated that resveratrol, caffeic acid, and tannic acid in stored blood could decrease the sensitivity to oxidation of erythrocytes in vitro but did not exhibit such effects on CA activity. PMID- 27413741 TI - Effects of Low-Flow Sevoflurane Anesthesia on Pulmonary Functions in Patients Undergoing Laparoscopic Abdominal Surgery. AB - Objective. The aim of this prospective, randomized study was to investigate the effects of low-flow sevoflurane anesthesia on the pulmonary functions in patients undergoing laparoscopic cholecystectomy. Methods. Sixty American Society of Anesthesiologists (ASA) physical status classes I and II patients scheduled for elective laparoscopic cholecystectomy were included in the study. Patients were randomly allocated to two study groups: high-flow sevoflurane anesthesia group (Group H, n = 30) and low-flow sevoflurane anesthesia group (Group L, n = 30). The fresh gas flow rate was of 4 L/min in high-flow sevoflurane anesthesia group and 1 L/min in low-flow sevoflurane anesthesia group. Heart rate (HR), mean arterial blood pressure (MABP), peripheral oxygen saturation (SpO2), and end tidal carbon dioxide concentration (ETCO2) were recorded. Pulmonary function tests were performed before and 2, 8, and 24 hours after surgery. Results. There was no significant difference between the two groups in terms of HR, MABP, SpO2, and ETCO2. Pulmonary function test results were similar in both groups at all measurement times. Conclusions. The effects of low-flow sevoflurane anesthesia on pulmonary functions are comparable to high-flow sevoflurane anesthesia in patients undergoing laparoscopic cholecystectomy. PMID- 27413742 TI - Contaminants of Emerging Concern: From the Detection to Their Effects on Human Health. PMID- 27413743 TI - A Novel Homozygous p.L539F Mutation Identified in PINK1 Gene in a Moroccan Patient with Parkinsonism. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ten of fifteen causative genes linked to familial forms of PD have been reported to cause autosomal recessive forms. Among them, mutations in the PTEN-induced kinase 1 (PINK1) gene were shown to be responsible for a phenotype characterized by early onset, good response to levodopa, and a benign course. Using chromosomal microarray analysis and Sanger sequencing, we identified a homozygous G/C substitution in a 58-year-old Moroccan man diagnosed with recessive inherited Parkinson's disease. This G-to-C transition occurred at position 1617 leading to an amino acid change L/F at position 539 located in highly conserved motif in the C terminal sequence of PINK1. Interestingly, the c.1617G>C substitution is absent in 192 ethnically matched control chromosomes. Our findings have shown that the p.L539F is a novel mutation located in the C terminal sequence of the PINK1 protein that could be pathogenic and responsible for a clinical phenotype resembling idiopathic Parkinson's disease with rapid progression and early cognitive impairment. PMID- 27413745 TI - Effects of Total Alkaloids of Sophora alopecuroides on Biofilm Formation in Staphylococcus epidermidis. AB - Staphylococcus epidermidis (S. epidermidis) is an opportunistic pathogen with low pathogenicity and a cause of the repeated outbreak of bovine mastitis in veterinary clinical settings. In this report, a biofilm model of S. epidermidis was generated and the minimal inhibitory concentration (MIC) and sub-MIC (SMIC) on bacterial cultures were assessed for the following agents: total alkaloids of Sophora alopecuroides (TASA), ciprofloxacin (CIP), and erythromycin (ERY). The formation and characteristic parameters of biofilm were analyzed in terms of XTT assay, silver staining, and confocal laser scanning microscope (CLSM). Results showed that a sub-MIC of TASA could inhibit 50% biofilm of bacterial activity, while 250-fold MIC of CIP and ERY MICs only inhibited 50% and 47% of biofilm formation, respectively. All three agents could inhibit the biofilm formation at an early stage, but TASA showed a better inhibitory effect on the late stage of biofilm thickening. A morphological analysis using CLSM further confirmed the destruction of biofilm by these agents. These results thus suggest that TASA has an inhibitory effect on biofilm formation of clinic S. epidermidis, which may be a potential agent warranted for further study on the treatment prevention of infection related to S. epidermidis in veterinary clinic. PMID- 27413744 TI - Mechanoregulation of Wound Healing and Skin Homeostasis. AB - Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force which supports effective healing. A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds. In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy. Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance. The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing. The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology. The study also defines how and what mechanical changes influence tissue regeneration and wound healing. The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study. PMID- 27413746 TI - Bone Regeneration in Iliac Crestal Defects: An Experimental Study on Sheep. AB - Background. Oral rehabilitation of partially fully edentulous patients with dental implants has become a routine procedure in clinical practice. In a site with a lack of bone GBR is a surgical procedure that provides an augmentation in terms of volume for the insertion of dental implants. Materials and Methods. In the iliac crest of six sheep 4 defects were created where an implant was inserted, three of them with different biomaterials and a control site. All animals were sacrificed after a 4-month healing period. All specimens were processed and analyzed with histomorphometry. Statistical evaluation was done to evaluate percentage of bone defect filled by new bone. Results. All experimental groups showed an increase of the new bone. Higher and highly statistically significant differences were found in the percentages of bone defect filled by new bone in group filled with corticocancellous 250-1000 microns particulate porcine bone mix. Conclusions. This study demonstrates that particulate porcine bone mix and porcine corticocancellous collagenate prehydrated bone mix when used as scaffold are able to induce bone regeneration. Moreover, these data suggest that these biomaterials have higher biocompatibility and are capable of inducing faster and greater bone formation. PMID- 27413747 TI - High Glucose-Induced PC12 Cell Death by Increasing Glutamate Production and Decreasing Methyl Group Metabolism. AB - Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM) or control (25 mM) groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine) may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism. Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism. PMID- 27413748 TI - Expression of HIF-2alpha and VEGF in Cervical Squamous Cell Carcinoma and Its Clinical Significance. AB - CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2alpha and VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2alpha and VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2alpha and VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2alpha and VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2alpha and VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2alpha and VEGF mRNA expression. So, HIF-2alpha and VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis. PMID- 27413749 TI - Assessment of Tree Leaves Flakes Mixed with Crude Glycerol as a Bioenergy Source. AB - The gasification and combustion of dry tree leaves and the cogasification of dry tree leaves soaking crude glycerol were studied experimentally. An updraft fixed bed gasification and combustion system was built. The operation was conducted at different air to fuel ratios. Results show more stable combustion and more effective heat transfer to furnace walls for the cases when tree leaves flakes are mixed with 20 percent (on mass basis) of crude glycerol, as compared with the case when only dry tree leaves are used as fuel. TGA analysis was also conducted for the two fuels used under both air and nitrogen environments. For the crude glycerol, four phases of pyrolysis and gasification were noticed under either of the two surrounding gaseous media (air or nitrogen). For the dry tree leaves, the pyrolysis under nitrogen shows only a simple smooth pyrolysis and gasification curve without showing the different distinct phases that were otherwise identified when the pyrolysis is conducted under air environment. Moreover, the air TGA results lead to more gasification due to the char oxidation at high temperatures. DTG results are also presented and discussed. PMID- 27413750 TI - Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia. AB - Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID- 27413751 TI - Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection. AB - Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. PMID- 27413752 TI - The Effect of Glutamate Receptor Agonists on Mouse Retinal Astrocyte [Ca(2+)]i. AB - Calcium-imaging techniques were used to determine if mouse retinal astrocytes in situ respond to agonists of ionotropic (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid, AMPA; N-methyl-D-aspartate, NMDA) and metabotropic (S 3,5-dihydroxyphenylglycine, DHPG; trans-1-amino-1,3-cyclopentanedicarboxylic acid, ACPD) glutamate receptors. In most cases we found no evidence that retinal astrocyte intracellular calcium ion concentration ([Ca(2+)]i) increased in response to these glutamate agonists. The one exception was AMPA that increased [Ca(2+)]i in some, but not all, mouse retinal astrocytes in situ. However, AMPA did not increase [Ca(2+)]i in mouse retinal astrocytes in vitro, suggesting that the effect of AMPA in situ may be indirect. PMID- 27413753 TI - Comparisons of Auditory Performance and Speech Intelligibility after Cochlear Implant Reimplantation in Mandarin-Speaking Users. AB - Objectives. We evaluated the causes, hearing, and speech performance before and after cochlear implant reimplantation in Mandarin-speaking users. Methods. In total, 589 patients who underwent cochlear implantation in our medical center between 1999 and 2014 were reviewed retrospectively. Data related to demographics, etiologies, implant-related information, complications, and hearing and speech performance were collected. Results. In total, 22 (3.74%) cases were found to have major complications. Infection (n = 12) and hard failure of the device (n = 8) were the most common major complications. Among them, 13 were reimplanted in our hospital. The mean scores of the Categorical Auditory Performance (CAP) and the Speech Intelligibility Rating (SIR) obtained before and after reimplantation were 5.5 versus 5.8 and 3.7 versus 4.3, respectively. The SIR score after reimplantation was significantly better than preoperation. Conclusions. Cochlear implantation is a safe procedure with low rates of postsurgical revisions and device failures. The Mandarin-speaking patients in this study who received reimplantation had restored auditory performance and speech intelligibility after surgery. Device soft failure was rare in our series, calling attention to Mandarin-speaking CI users requiring revision of their implants due to undesirable symptoms or decreasing performance of uncertain cause. PMID- 27413754 TI - Activation of GPR119 Stimulates Human beta-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets. AB - Using humanized mice with functional human islets, we investigated whether activating GPR119 by PSN632408, a small molecular agonist, can stimulate human beta-cell regeneration in vivo. Human islets were transplanted under the left kidney capsule of immunodeficient mice with streptozotocin- (STZ-) induced diabetes. The recipient mice were treated with PSN632408 or vehicle and BrdU daily. Human islet graft function in the mice was evaluated by nonfasting glucose levels, oral glucose tolerance, and removal of the grafts. Immunostaining for insulin, glucagon, and BrdU or Ki67 was performed in islet grafts to evaluate alpha- and beta-cell replication. Insulin and CK19 immunostaining was performed to evaluate beta-cell neogenesis. Four weeks after human islet transplantation, 71% of PSN632408-treated mice achieved normoglycaemia compared with 24% of vehicle-treated mice. Also, oral glucose tolerance was significantly improved in the PSN632408-treated mice. PSN632408 treatment significantly increased both human alpha- and beta-cell areas in islet grafts and stimulated alpha- and beta cell replication. In addition, beta-cell neogenesis was induced from pancreatic duct cells in the islet grafts. Our results demonstrated that activation of GPR119 increases beta-cell mass by stimulating human beta-cell replication and neogenesis. Therefore, GPR119 activators may qualify as therapeutic agents to increase human beta-cell mass in patients with diabetes. PMID- 27413755 TI - Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy. AB - Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition-mainly cardiovascular ones-and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new "gold standard" biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN. PMID- 27413756 TI - Aptamers: A Feasible Technology in Cancer Immunotherapy. AB - Aptamers are single-chained RNA or DNA oligonucleotides (ODNs) with three dimensional folding structures which allow them to bind to their targets with high specificity. Aptamers normally show affinities comparable to or higher than that of antibodies. They are chemically synthesized and therefore less expensive to manufacture and produce. A variety of aptamers described to date have been shown to be reliable in modulating immune responses against cancer by either blocking or activating immune receptors. Some of them have been conjugated to other molecules to target the immune system and reduce off-target side effects. Despite the success of first-line treatments against cancer, the elevated number of relapsing cases and the tremendous side effects shown by the commonly used agents hinder conventional treatments against cancer. The advantages provided by aptamers could enhance the therapeutic index of a given strategy and therefore enhance the antitumor effect. Here we recapitulate the provided benefits of aptamers with immunomodulatory activity described to date in cancer therapy and the benefits that aptamer-based immunotherapy could provide either alone or combined with first-line treatments in cancer therapy. PMID- 27413757 TI - Preexisting Antibodies to an F(ab')2 Antibody Therapeutic and Novel Method for Immunogenicity Assessment. AB - Anti-therapeutic antibodies (ATAs) may impact drug exposure and activity and induce immune complex mediated toxicity; therefore the accurate measurement of ATA is important for the analysis of drug safety and efficacy. Preexisting ATAs to the hinge region of anti-Delta like ligand 4 (anti-DLL4) F(ab')2, a potential antitumor therapeutic, were detected in cynomolgus monkey serum, which presented a challenge in developing assays for detecting treatment induced ATA. A total ATA assay was developed using a bridging ELISA that detected both anti-CDR and anti framework ATA including anti-hinge reactivity. A competition assay that could detect 500 ng/mL of anti-CDR ATA in the presence of preexisting ATA was also developed to determine ATA specific to the anti-DLL4 F(ab')2 CDR using anti-DLL4 F(ab')2 and a control F(ab')2. We used these assay methods in a cynomolgus monkey in vivo study to successfully evaluate total and anti-CDR ATA. The preexisting anti-hinge reactivity was also observed to a lesser extent in human serum, and a similar approach could be applied for specific immunogenicity assessment in clinical trials. PMID- 27413758 TI - A Modified NK Cell Degranulation Assay Applicable for Routine Evaluation of NK Cell Function. AB - Natural killer (NK) cells play important role in innate immunity against tumors and viral infections. Studies show that lysosome-associated membrane protein-1 (LAMP-1, CD107a) is a marker for degranulation of NK and cytotoxic T cells and its expression is a sensitive marker for the cytotoxic activity determination. The conventional methods of determination of CD107a on NK cells involve use of peripheral blood mononuclear cells (PBMC) or pure NK cells and K562 cells as stimulants. Thus, it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line. We have designed a flow cytometric assay to determine CD107a on NK cells using whole blood, eliminating the need for isolation of PBMC or isolate NK cells. This assay uses phorbol-12-myristate-13-acetate (PMA) and calcium ionophore (Ca(2+)-ionophore) instead of K562 cells for stimulation and thus does not require specialized cell culture laboratory. CD107a expression on NK cells using modified NK cell degranulation assay compared to the conventional assay was significantly elevated (p < 0.0001). It was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis (FHL) with defect in exocytosis. This assay is rapid, cost effective, and reproducible and requires significantly less volume of blood which is important for clinical evaluation of NK cells. PMID- 27413759 TI - The Mannose Receptor Is Involved in the Phagocytosis of Mycobacteria-Induced Apoptotic Cells. AB - Upon Mycobacterium tuberculosis infection, macrophages may undergo apoptosis, which has been considered an innate immune response. The pathways underlying the removal of dead cells in homeostatic apoptosis have been extensively studied, but little is known regarding how cells that undergo apoptotic death during mycobacterial infection are removed. This study shows that macrophages induced to undergo apoptosis with mycobacteria cell wall proteins are engulfed by J-774A.1 monocytic cells through the mannose receptor. This demonstration was achieved through assays in which phagocytosis was inhibited with a blocking anti-mannose receptor antibody and with mannose receptor competitor sugars. Moreover, elimination of the mannose receptor by a specific siRNA significantly diminished the expression of the mannose receptor and the phagocytosis of apoptotic cells. As shown by immunofluorescence, engulfed apoptotic bodies are initially located in Rab5-positive phagosomes, which mature to express the phagolysosome marker LAMP1. The phagocytosis of dead cells triggered an anti-inflammatory response with the production of TGF-beta and IL-10 but not of the proinflammatory cytokines IL-12 and TNF-alpha. This study documents the previously unreported participation of the mannose receptor in the removal of apoptotic cells in the setting of tuberculosis (TB) infection. The results challenge the idea that apoptotic cell phagocytosis in TB has an immunogenic effect. PMID- 27413760 TI - Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition. AB - In organ transplantation, alloantigens are taken up by antigen presenting cells and presented via the indirect pathway to T-cells which in turn can induce allograft rejection. Monitoring of these T-cells is of major importance; however no reliable assay is available to routinely monitor indirect allorecognition. Recently we showed that HLA monomers can be successfully used to monitor indirect allorecognition. Targeting antigens to endocytic receptors on antigen presenting cells may further enhance the presentation of antigens via HLA class II and improve the efficiency of this assay. In the current study we explored targeting of HLA monomers to either CD89 expressing monocytes or mannose receptor expressing dendritic cells. Monomer-antibody complexes were generated using biotin-labeled monomers and avidin labeling of the antibodies. We demonstrate that targeting the complexes to these receptors resulted in a dose-dependent HLA class II mediated presentation to a T-cell clone. The immune-complexes were efficiently taken up and presented to T-cells. However, the level of T-cell reactivity was similar to that when only exogenous antigen was added. We conclude that HLA-A2 monomers targeted for presentation through CD89 on monocytes or mannose receptor on dendritic cells lead to proper antigen presentation but do not enhance indirect allorecognition via HLA-DR. PMID- 27413761 TI - Identification of Novel Vaccine Candidates against Campylobacter through Reverse Vaccinology. AB - Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union. Human cases are mainly due to Campylobacter jejuni or Campylobacter coli, and contamination is associated with the handling and/or consumption of poultry meat. In fact, poultry constitutes the bacteria's main reservoir. A promising way of decreasing the incidence of campylobacteriosis in humans would be to decrease avian colonization. Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinal Campylobacter load in chickens. It is essential to identify and characterize new vaccine antigens. This study applied the reverse vaccinology approach to detect new vaccine candidates. The main criteria used to select immune proteins were localization, antigenicity, and number of B-epitopes. Fourteen proteins were identified as potential vaccine antigens. In vitro and in vivo experiments now need to be performed to validate the immune and protective power of these newly identified antigens. PMID- 27413762 TI - Immunoregulatory Role of HLA-G in Allergic Diseases. AB - Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID- 27413763 TI - Elevated Concentration of Defensins in Hepatitis C Virus-Infected Patients. AB - Hepatitis C virus (HCV) is the major etiological agent of human non-A and non-B hepatitis, affecting around 180 million people worldwide. Defensins, small cysteine-rich cationic peptides, are shown to have potent antibacterial, antiviral, and antifungal properties. Defensins can be found in both normal and microbial infected patients, at variable concentrations. Notably, viral infections are often associated with elevated concentrations of defensins. The current study aimed to estimate the concentrations of total, alpha-, and beta defensins in serum taken from normal and HCV-infected patients. 12 healthy (noninfected) and 34 HCV-infected patients were enrolled. Standardized immunoassay kits were used to obtain serum concentrations of defensins. The obtained results were calibrated against kit standard reagents. Total defensin concentrations in HCV-infected patients were significantly higher (2- to 105 fold) compared to healthy individuals. The concentrations of alpha-defensins were also significantly elevated in the HCV-infected patients (31-1398 ng/50 MUL). However, concentrations of beta-defensins ranged from 44.5 ng/50 MUL to 1056 ng/50 MUL. The results did not reveal differences in serum defensin concentration between male and female HCV-infected patients. A-defensin concentration of >=250 ng/50 MUL was found to contain more beta-defensins than total defensins and alpha defensins. This study concludes, for the first time, that serum defensin levels are elevated in HCV-infected patients. PMID- 27413765 TI - Donor-Derived Coccidioides immitis Endocarditis and Disseminated Infection in the Setting of Solid Organ Transplantation. AB - Background. Endocarditis is a rare manifestation of infection with Coccidioides. This is the first reported case of donor-derived Coccidioides endocarditis obtained from a heart transplant. Methods. We present a unique case of donor derived Coccidioides immitis endocarditis and disseminated infection in a heart transplant patient. We also conducted a review of the literature to identify other cases of donor-derived coccidioidomycosis in solid organ transplant recipients and reviewed their clinical characteristics. Results. Fifteen prior cases of donor-derived coccidioidomycosis were identified. A majority of these cases were diagnosed by positive culture (83%). Mortality was high at 58%. Conclusions. Clinicians should maintain a high index of suspicion for disseminated coccidioidomycosis in patients who received transplants with organs from donors with a history of residing in endemic regions. PMID- 27413764 TI - Immune Regulation and Antitumor Effect of TIM-1. AB - T cells play an important role in antitumor immunity, and the T cell immunoglobulin domain and the mucin domain protein-1 (TIM-1) on its surface, as a costimulatory molecule, has a strong regulatory effect on T cells. TIM-1 can regulate and enhance type 1 immune response of tumor association. Therefore, TIM 1 costimulatory pathways may be a promising therapeutic target in future tumor immunotherapy. This review describes the immune regulation and antitumor effect of TIM-1. PMID- 27413766 TI - Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation. AB - Emerging all-optical methods provide unique possibilities for noninvasive studies of physiological processes at the cellular and subcellular scale. On the one hand, superresolution microscopy enables observation of living samples with nanometer resolution. On the other hand, light can be used to stimulate cells due to the advent of optogenetics and photolyzable neurotransmitters. To exploit the full potential of optical stimulation, light must be delivered to specific cells or even parts of cells such as dendritic spines. This can be achieved with computer generated holography (CGH), which shapes light to arbitrary patterns by phase-only modulation. We demonstrate here in detail how CGH can be incorporated into a stimulated emission depletion (STED) microscope for photostimulation of neurons and monitoring of nanoscale morphological changes. We implement an original optical system to allow simultaneous holographic photostimulation and superresolution STED imaging. We present how synapses can be clearly visualized in live cells using membrane stains either with lipophilic organic dyes or with fluorescent proteins. We demonstrate the capabilities of this microscope to precisely monitor morphological changes of dendritic spines after stimulation. These all-optical methods for cell stimulation and monitoring are expected to spread to various fields of biological research in neuroscience and beyond. PMID- 27413767 TI - Probing amyloid protein aggregation with optical superresolution methods: from the test tube to models of disease. AB - The misfolding and self-assembly of intrinsically disordered proteins into insoluble amyloid structures are central to many neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Optical imaging of this self-assembly process in vitro and in cells is revolutionizing our understanding of the molecular mechanisms behind these devastating conditions. In contrast to conventional biophysical methods, optical imaging and, in particular, optical superresolution imaging, permits the dynamic investigation of the molecular self assembly process in vitro and in cells, at molecular-level resolution. In this article, current state-of-the-art imaging methods are reviewed and discussed in the context of research into neurodegeneration. PMID- 27413768 TI - Semiautomatic tumor segmentation with multimodal images in a conditional random field framework. AB - Volumetric medical images of a single subject can be acquired using different imaging modalities, such as computed tomography, magnetic resonance imaging (MRI), and positron emission tomography. In this work, we present a semiautomatic segmentation algorithm that can leverage the synergies between different image modalities while integrating interactive human guidance. The algorithm provides a statistical segmentation framework partly automating the segmentation task while still maintaining critical human oversight. The statistical models presented are trained interactively using simple brush strokes to indicate tumor and nontumor tissues and using intermediate results within a patient's image study. To accomplish the segmentation, we construct the energy function in the conditional random field (CRF) framework. For each slice, the energy function is set using the estimated probabilities from both user brush stroke data and prior approved segmented slices within a patient study. The progressive segmentation is obtained using a graph-cut-based minimization. Although no similar semiautomated algorithm is currently available, we evaluated our method with an MRI data set from Medical Image Computing and Computer Assisted Intervention Society multimodal brain segmentation challenge (BRATS 2012 and 2013) against a similar fully automatic method based on CRF and a semiautomatic method based on grow-cut, and our method shows superior performance. PMID- 27413769 TI - Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation. AB - Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-based method called PyMAN (PTSE model based on artificial neural network) accounting for the current used in stimulation, the three-dimensional electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the GPm have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was 0.78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning. PMID- 27413770 TI - Fast nonlinear regression method for CT brain perfusion analysis. AB - Although computed tomography (CT) perfusion (CTP) imaging enables rapid diagnosis and prognosis of ischemic stroke, current CTP analysis methods have several shortcomings. We propose a fast nonlinear regression method with a box-shaped model (boxNLR) that has important advantages over the current state-of-the-art method, block-circulant singular value decomposition (bSVD). These advantages include improved robustness to attenuation curve truncation, extensibility, and unified estimation of perfusion parameters. The method is compared with bSVD and with a commercial SVD-based method. The three methods were quantitatively evaluated by means of a digital perfusion phantom, described by Kudo et al. and qualitatively with the aid of 50 clinical CTP scans. All three methods yielded high Pearson correlation coefficients ([Formula: see text]) with the ground truth in the phantom. The boxNLR perfusion maps of the clinical scans showed higher correlation with bSVD than the perfusion maps from the commercial method. Furthermore, it was shown that boxNLR estimates are robust to noise, truncation, and tracer delay. The proposed method provides a fast and reliable way of estimating perfusion parameters from CTP scans. This suggests it could be a viable alternative to current commercial and academic methods. PMID- 27413771 TI - Medications Discovery: Importance of Assessment of Drug Self Administration Dose Effect Curves. PMID- 27413772 TI - Little Cigars and Cigarillos: Users, Perceptions, and Reasons for Use. AB - OBJECTIVE: This study examines little cigar and cigarillo (LCC) adult user characteristics, perceived addictiveness, use and importance of flavors, intentions to continue use, and reasons for use to inform prevention efforts and regulatory policy. METHODS: Data come from the 2014 Tobacco Products and Risk Perceptions Survey of a national probability sample of 5717 US adults, conducted online, June-November, 2014. The analytic sample consisted of 141 current LCC users. RESULTS: Current LCC smokers were more likely to be male, younger, black or Hispanic, lower SES, current cigarette smokers, and to report poorer health than non-smokers. Perceived addictiveness was low overall, with 73.6% considering themselves "not at all" addicted, although female LCC users and dual users of cigarettes were more likely to consider themselves addicted to LCCs. Use of flavored LCCs was widespread. Flavors were cited as important reasons for use, especially among younger users, as were favorable comparisons with affordability and burn time of cigarettes. CONCLUSIONS: Most LCC users do not perceive themselves addicted to LCCs. Users report being influenced most by flavorings and affordability, indicating that appropriate regulations and education to improve health perceptions could help reduce use of these harmful products. PMID- 27413773 TI - Production and Catalytic Properties of Amylases from Lichtheimia ramosa and Thermoascus aurantiacus by Solid-State Fermentation. AB - The present study compared the production and the catalytic properties of amylolytic enzymes obtained from the fungi Lichtheimia ramosa (mesophilic) and Thermoascus aurantiacus (thermophilic). The highest amylase production in both fungi was observed in wheat bran supplemented with nutrient solution (pH 4.0) after 96 hours of cultivation, reaching 417.2 U/g of dry substrate (or 41.72 U/mL) and 144.5 U/g of dry substrate (or 14.45 U/mL) for L. ramosa and T. aurantiacus, respectively. The enzymes showed higher catalytic activity at pH 6.0 at 60 degrees C. The amylases produced by L. ramosa and T. aurantiacus were stable between pH 3.5-10.5 and pH 4.5-9.5, respectively. The amylase of L. ramosa was stable at 55 degrees C after 1 hour of incubation, whereas that of T. aurantiacus maintained 60% of its original activity under the same conditions. Both enzymes were active in the presence of ethanol. The enzymes hydrolyzed starch from different sources, with the best results obtained with corn starch. The enzymatic complex produced by L. ramosa showed dextrinizing and saccharifying potential. The enzymatic extract produced by the fungus T. aurantiacus presented only saccharifying potential, releasing glucose monomers as the main hydrolysis product. PMID- 27413775 TI - Improving Surgical Access in Rural Africa through a Surgical Camp Model. AB - Introduction. Surgical camps are preplanned activities where volunteer surgical teams congregate at specified place(s) and perform a wide range of mostly elective procedures for a limited period of time. This is usually at no cost to the patients, who belong to vulnerable (poor and hard to reach) communities. We describe a surgical camp model and its challenges as a means of improving access to surgical services. Methods. A cross-sectional descriptive study. Data from a recent Association of Surgeons of Uganda surgical camp were collected and analyzed for demographics, costs, procedure types, and rates and, in addition, challenges encountered and solutions. Personnel that participated in this exercise included specialist surgeons, surgical residents, medical officers, clinical officers, anesthetists, and theater nurses (a total of 121 staff). Results. In total, 551 procedures were performed during a four-day-long camp. Mean age was 35 years (SD 23), M : F ratio was 2 : 1. Herniorrhaphy, skin lump excision, hydrocelectomy, and thyroidectomy formed 81% of all the procedures. Average cost per procedure was $73 USD. Conclusion. Surgical camps offer increased access to surgical services to vulnerable populations. Hernias and goiters were most common. Surgical camps should become an integral part of the Health Service delivery in low-resourced environments. PMID- 27413774 TI - Safety and Complications of Medical Thoracoscopy. AB - Objectives. To highlight the possible complications of medical thoracoscopy (MT) and how to avoid them. Methods. A retrospective and prospective analysis of 127 patients undergoing MT in Nagoya Medical Center (NMC) and Toyota Kosei Hospital. The data about complications was obtained from the patients, notes on the computer system, and radiographs. Results. The median age was 71.0 (range, 33.0 92.0) years and 101 (79.5%) were males. The median time with chest drain after procedure was 7.0 (range, 0.0-47.0) days and cases with talc poudrage were 30 (23.6%). Malignant histology was reported in 69 (54.3%), including primary lung cancer in 35 (27.5), mesothelioma in 18 (14.2), and metastasis in 16 (12.6). 58 (45.7%) revealed benign pleural diseases and TB was diagnosed in 15 (11.8%). 21 (16.5%) patients suffered from complications including lung laceration in 3 (2.4%), fever in 5 (3.9%) (due to hospital acquired infection (HAI) in 2, talc poudrage in 2, and malignancy in 1), HAI in 2 (1.6%), prolonged air-leak in 14 (11.0%), and subcutaneous emphysema in 1 (0.8%). Conclusions. MT is generally a safe procedure. Lung laceration is the most serious complication and should be managed well. HAI is of low risk and can be controlled by medical treatment. PMID- 27413777 TI - A Conversation with Hildegarde Heymann. PMID- 27413776 TI - Postdoc Labor Love. PMID- 27413778 TI - Designer Drug Detective Work. PMID- 27413779 TI - Nuphar Dimers: Crouching Sulfur, Hidden Reactivity. PMID- 27413780 TI - Meteoritic Amino Acids: Diversity in Compositions Reflects Parent Body Histories. AB - The analysis of amino acids in meteorites dates back over 50 years; however, it is only in recent years that research has expanded beyond investigations of a narrow set of meteorite groups (exemplified by the Murchison meteorite) into meteorites of other types and classes. These new studies have shown a wide diversity in the abundance and distribution of amino acids across carbonaceous chondrite groups, highlighting the role of parent body processes and composition in the creation, preservation, or alteration of amino acids. Although most chiral amino acids are racemic in meteorites, the enantiomeric distribution of some amino acids, particularly of the nonprotein amino acid isovaline, has also been shown to vary both within certain meteorites and across carbonaceous meteorite groups. Large l-enantiomeric excesses of some extraterrestrial protein amino acids (up to ~60%) have also been observed in rare cases and point to nonbiological enantiomeric enrichment processes prior to the emergence of life. In this Outlook, we review these recent meteoritic analyses, focusing on variations in abundance, structural distributions, and enantiomeric distributions of amino acids and discussing possible explanations for these observations and the potential for future work. PMID- 27413781 TI - Investigating the Complex Chemistry of Functional Energy Storage Systems: The Need for an Integrative, Multiscale (Molecular to Mesoscale) Perspective. AB - Electric energy storage systems such as batteries can significantly impact society in a variety of ways, including facilitating the widespread deployment of portable electronic devices, enabling the use of renewable energy generation for local off grid situations and providing the basis of highly efficient power grids integrated with energy production, large stationary batteries, and the excess capacity from electric vehicles. A critical challenge for electric energy storage is understanding the basic science associated with the gap between the usable output of energy storage systems and their theoretical energy contents. The goal of overcoming this inefficiency is to achieve more useful work (w) and minimize the generation of waste heat (q). Minimization of inefficiency can be approached at the macro level, where bulk parameters are identified and manipulated, with optimization as an ultimate goal. However, such a strategy may not provide insight toward the complexities of electric energy storage, especially the inherent heterogeneity of ion and electron flux contributing to the local resistances at numerous interfaces found at several scale lengths within a battery. Thus, the ability to predict and ultimately tune these complex systems to specific applications, both current and future, demands not just parametrization at the bulk scale but rather specific experimentation and understanding over multiple length scales within the same battery system, from the molecular scale to the mesoscale. Herein, we provide a case study examining the insights and implications from multiscale investigations of a prospective battery material, Fe3O4. PMID- 27413782 TI - Anion-pi Enzymes. AB - In this report, we introduce artificial enzymes that operate with anion-pi interactions, an interaction that is essentially new to nature. The possibility to stabilize anionic intermediates and transition states on an pi-acidic surface has been recently demonstrated, using the addition of malonate half thioesters to enolate acceptors as a biologically relevant example. The best chiral anion-pi catalysts operate with an addition/decarboxylation ratio of 4:1, but without any stereoselectivity. To catalyze this important but intrinsically disfavored reaction stereoselectively, a series of anion-pi catalysts was equipped with biotin and screened against a collection of streptavidin mutants. With the best hit, the S112Y mutant, the reaction occurred with 95% ee and complete suppression of the intrinsically favored side product from decarboxylation. This performance of anion-pi enzymes rivals, if not exceeds, that of the best conventional organocatalysts. Inhibition of the S112Y mutant by nitrate but not by bulky anions supports that contributions from anion-pi interactions exist and matter, also within proteins. In agreement with docking results, K121 is shown to be essential, presumably to lower the pK a of the tertiary amine catalyst to operate at the optimum pH around 3, that is below the pK a of the substrate. Most importantly, increasing enantioselectivity with different mutants always coincides with increasing rates and conversion, i.e., selective transition-state stabilization. PMID- 27413783 TI - Nucleic Acid Templated Chemical Reaction in a Live Vertebrate. AB - Nucleic acid templated reactions are enabled by the hybridization of probe reagent conjugates resulting in high effective reagent concentration and fast chemical transformation. We have developed a reaction that harnesses cellular microRNA (miRNA) to yield the cleavage of a linker releasing fluorogenic rhodamine in a live vertebrate. The reaction is based on the catalytic photoreduction of an azide by a ruthenium complex. We showed that this system reports specific expression of miRNA in living tissues of a vertebrate. PMID- 27413784 TI - Synthesis and Sulfur Electrophilicity of the Nuphar Thiaspirane Pharmacophore. AB - We describe a general method to synthesize the iminium tetrahydrothiophene embedded in the dimeric Nuphar alkaloids. In contrast to prior studies, the sulfur atom of the thiaspirane pharmacophore is shown to be electrophilic. This alpha-thioether reacts with thiophenol or glutathione at ambient temperature to cleave the C-S bond and form a disulfide. Rates of conversion are proportional to the corresponding ammonium ion pK a and exhibit half-lives less than 5 h at a 5 mM concentration of thiol. A simple thiophane analogue of the Nuphar dimers causes apoptosis at single-digit micromolar concentration and labels reactive cysteines at similar levels as the unsaturated iminium "warhead". Our experiments combined with prior observations suggest the sulfur of the Nuphar dimers can react as an electrophile in cellular environments and that sulfur-triggered retrodimerization can occur in the cell. PMID- 27413785 TI - First-Principles Monte Carlo Simulations of Reaction Equilibria in Compressed Vapors. AB - Predictive modeling of reaction equilibria presents one of the grand challenges in the field of molecular simulation. Difficulties in the study of such systems arise from the need (i) to accurately model both strong, short-ranged interactions leading to the formation of chemical bonds and weak interactions arising from the environment, and (ii) to sample the range of time scales involving frequent molecular collisions, slow diffusion, and infrequent reactive events. Here we present a novel reactive first-principles Monte Carlo (RxFPMC) approach that allows for investigation of reaction equilibria without the need to prespecify a set of chemical reactions and their ideal-gas equilibrium constants. We apply RxFPMC to investigate a nitrogen/oxygen mixture at T = 3000 K and p = 30 GPa, i.e., conditions that are present in atmospheric lightning strikes and explosions. The RxFPMC simulations show that the solvation environment leads to a significantly enhanced NO concentration that reaches a maximum when oxygen is present in slight excess. In addition, the RxFPMC simulations indicate the formation of NO2 and N2O in mole fractions approaching 1%, whereas N3 and O3 are not observed. The equilibrium distributions obtained from the RxFPMC simulations agree well with those from a thermochemical computer code parametrized to experimental data. PMID- 27413786 TI - Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement. AB - Sigmatropic rearrangements number among the most powerful complexity-building transformations in organic synthesis but have remained largely insensitive to enantioselective catalysis due to the diffuse nature of their transition structures. Here, we describe a synergistic ion-binding strategy for asymmetric catalysis of anionic sigmatropic rearrangements. This approach is demonstrated with the enantioselective [2,3]-Wittig rearrangement of alpha-allyloxy carbonyl compounds to afford highly enantioenriched homoallylic alcohol products. Chiral thiourea catalysts are shown to engage reactive anions and their countercations through a cooperative set of attractive, noncovalent interactions. Catalyst structure-reactivity-selectivity relationship studies and computational analyses provide insight into catalyst-substrate interactions responsible for enantioinduction and allude to the potential generality of this catalytic strategy. PMID- 27413787 TI - Catalytic Oxidation of Methane into Methanol over Copper-Exchanged Zeolites with Oxygen at Low Temperature. AB - The direct catalytic conversion of methane to liquid oxygenated compounds, such as methanol or dimethyl ether, at low temperature using molecular oxygen is a grand challenge in C-H activation that has never been met with synthetic, heterogeneous catalysts. We report the first demonstration of direct, catalytic oxidation of methane into methanol with molecular oxygen over copper-exchanged zeolites at low reaction temperatures (483-498 K). Reaction kinetics studies show sustained catalytic activity and high selectivity for a variety of commercially available zeolite topologies under mild conditions (e.g., 483 K and atmospheric pressure). Transient and steady state measurements with isotopically labeled molecules confirm catalytic turnover. The catalytic rates and apparent activation energies are affected by the zeolite topology, with caged-based zeolites (e.g., Cu-SSZ-13) showing the highest rates. Although the reaction rates are low, the discovery of catalytic sites in copper-exchanged zeolites will accelerate the development of strategies to directly oxidize methane into methanol under mild conditions. PMID- 27413789 TI - Typical Hus: Evidence of Acute Phase Complement Activation from a Daycare Outbreak. AB - The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by eculizumab in vitro, an effect that was replicated in vitro utilizing Shiga toxin as a stimulus of complement activation in normal serum. Our report suggests that complement blockade may be effective in the treatment of STEC-HUS when initiated early in the disease. Given the epidemic nature of the disease that limits the feasibility of randomized clinical trials, further studies are needed to determine the value of early eculizumab treatment in STEC-HUS. PMID- 27413790 TI - Lee Rosen, PhD: SRO, Advocate, and Friend. PMID- 27413788 TI - Endocannabinoids in the Gut. AB - Cannabis has been used medicinally for centuries to treat a variety of disorders, including those associated with the gastrointestinal tract. The discovery of our bodies' own "cannabis-like molecules" and associated receptors and metabolic machinery - collectively called the endocannabinoid system - enabled investigations into the physiological relevance for the system, and provided the field with evidence of a critical function for this endogenous signaling pathway in health and disease. Recent investigations yield insight into a significant participation for the endocannabinoid system in the normal physiology of gastrointestinal function, and its possible dysfunction in gastrointestinal pathology. Many gaps, however, remain in our understanding of the precise neural and molecular mechanisms across tissue departments that are under the regulatory control of the endocannabinoid system. This review highlights research that reveals an important - and at times surprising - role for the endocannabinoid system in the control of a variety of gastrointestinal functions, including motility, gut-brain mediated fat intake and hunger signaling, inflammation and gut permeability, and dynamic interactions with gut microbiota. PMID- 27413791 TI - To the Editor. PMID- 27413792 TI - In Response: How Long Should Insulin be Used Once a Vial is Opened? PMID- 27413793 TI - [Typhoid vaccination: Administering another dose 3 years after the first one is efficient]. PMID- 27413794 TI - [Measles kills children...far beyond skin rash!]. PMID- 27413795 TI - WHO publishes viral hepatitis surveillance guide. PMID- 27413796 TI - Esophagitis Dissecans Superficialis in a 49- year-old woman. PMID- 27413797 TI - Deadpool: using pop culture for cancer advocacy. PMID- 27413798 TI - [RESEARCH PROGRESS OF MECHANISMS OF MESENCHYMAL STEM CELLS-DERIVED EXOSOMES IN TISSUE REPAIR]. AB - OBJECTIVE: To review the mechanisms of bioactive substances of mesenchymal stem cells-derived exosomes (MEX) in tissue repair and analyze the therapeutic values of MEX. METHODS: Recent relevant literature about MEX for tissue repair was extensively reviewed and analyzed. RESULTS: The diameter of exosomes ranges from 30 to 100 nm which contain an abundance of bioactive substances, such as mRNA, microRNA, and protein. The majority of the exact bioactive substances in MEX, which are therapeutically beneficial to a wide range of diseases, are still unclear. CONCLUSION: Bioactive substances contained in the MEX have repairing effect in tissue injury, which could provide a new insight for the clinical treatment of tissue damage. However, further studies are required to investigate the individual differences of MEX and the possible risk of accelerating cancer progression of MEX. PMID- 27413801 TI - The Fungus Trichoderma Regulates Submerged Conidiation Using the Steroid Pregnenolone. AB - In previous work, we evolved a population of Trichoderma citrinoviride in liquid cultures to speed up its asexual development cycle. The evolved population, called T-6, formed conidia 3 times sooner and in >1000-fold greater numbers. Here, we identify the steroid pregnenolone as a molecular signal for this different behavior. Media in which the ancestral T. citrinoviride population was grown (called ancestral spent media) contained a submerged conidiation inhibitor. Growing the evolved population T-6 in ancestral spent media eliminated the abundant formation of conidia. This inhibition depended on the amount and age of the ancestral spent medium and the time that the ancestral spent medium was added to the T-6 culture. Fractionation of the ancestral spent medium identified a hydrophobic inhibiting compound with a molecular weight less than 2000 g/mol. A combination of GC-MS, ELISA, and reaction with cholesterol oxidase identified it as pregnenolone. The addition of pregnenolone to cultures of T-6 inhibited submerged conidiation by inhibiting formation of conidiophores, while 10 other analogous steroids did not. Pregnenolone also inhibited submerged conidiation of Fusarium graminearum PH-1, a plant pathogen that causes head blight in wheat and barley. This identification of steroids as signal molecules in fungi creates opportunities to disrupt this signaling to control fungal behavior. PMID- 27413802 TI - Drug-like Antagonists of P2Y Receptors-From Lead Identification to Drug Development. AB - P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators of P2Y receptors, although to date only a limited number of small molecule P2Y receptor antagonists have been approved by drug/medicines agencies. This Perspective reviews the known P2Y receptor antagonists, highlighting oral drug-like receptor antagonists, and considers future opportunities for the development of small molecules for clinical evaluation. PMID- 27413804 TI - Parental attachment insecurity and parenting stress: The mediating role of parents' perceived impact of children's diabetes on the family. AB - INTRODUCTION: Caring for a child with diabetes is a demanding and potentially stressful task for parents. Although secure attachment can be considered a resilience factor that helps an individual to cope with stressful life events, the idea that secure parents are better able to cope with a child's chronic health condition, such as diabetes, has rarely been investigated. Therefore, the aim of this study was to investigate whether attachment-related anxiety and avoidance are associated with parenting stress in parents of children and adolescents with diabetes and whether this association is mediated by parents' perception of the impact of diabetes on the family and moderated by children's age and duration of diabetes. METHOD: A sample of 105 parents (92.4% mothers) completed self-report measures of attachment, parenting stress, and perceived impact. RESULTS: Higher levels of attachment avoidance (but not anxiety) were associated with higher levels of parenting stress through an increased negative perception of the impact of diabetes. DISCUSSION: This study suggests that parents with higher levels of avoidance are at higher risk of experiencing greater parenting stress and perceiving their child's condition as more burdensome. (PsycINFO Database Record PMID- 27413803 TI - A Chimeric ATP-Linked Nucleotide Enables Luminescence Signaling of Damage Surveillance by MTH1, a Cancer Target. AB - The enzyme MTH1 cleanses the cellular nucleotide pool of oxidatively damaged 8 oxo-dGTP, preventing mutagenesis by this nucleotide. The enzyme is considered a promising therapeutic target; however, methods to measure its activity are indirect and laborious and have low sensitivity. Here we describe a novel ATP linked chimeric nucleotide (ARGO) that enables luminescence signaling of the enzymatic reaction, greatly simplifying the measurement of MTH1 activity. We show that the reporting system can be used to identify inhibitors of MTH1, and we use it to quantify enzyme activity in eight cell lines and in colorectal tumor tissue. The ARGO reporter is likely to have considerable utility in the study of the biology of MTH1 and potentially in analyzing patient samples during clinical testing. PMID- 27413805 TI - Outcomes of a 6-week cognitive-behavioral and mindfulness group intervention in primary care. AB - INTRODUCTION: Cognitive-behavioral and mindfulness-based interventions are established treatments for depressive and anxiety disorders; however, there is a lack of research for these interventions in primary care settings. The current study evaluates an evidence-based group intervention provided to primary care patients with a variety of mood and anxiety concerns. METHOD: Participants included 54 adult primary care patients who attended at least four sessions of a six-session cognitive-behavioral and mindfulness group. A total of nine separate groups were conducted, all of which were colocated within the primary care setting. Major depressive disorder and generalized anxiety disorder were the most common psychiatric conditions, with approximately 56% of the sample having one or more chronic medical conditions. Self-report measures of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Questionnaire 7) were completed at each session. RESULTS: Significant improvements were noted on self-reported measures of depression and anxiety when comparing pre- and posttreatment assessment measures with large effect sizes. DISCUSSION: A brief, principle-based cognitive-behavioral and mindfulness group intervention delivered in primary care was associated with improved symptoms across a range of patient presentations. Evidence-based group interventions in primary care settings have the benefits of increased access and cost-effectiveness. (PsycINFO Database Record PMID- 27413806 TI - Lo sviluppo del controllo delle infezioni in Italia. PMID- 27413807 TI - Ruolo della cute nelle infezioni nosocomiali: una rassegna. PMID- 27413808 TI - Ruolo degli antisettici nel controllo delle infezioni nosocomiali. PMID- 27413809 TI - L'uso degli antisettici nel lavaggio delle mani del personale medico. PMID- 27413810 TI - Disinfezione corporea totale preoperatoria (opinione Svedese). PMID- 27413812 TI - Young female cancer patients' experiences with fertility counselling and fertility preservation-a qualitative small-scale study within the Danish health care setting. AB - INTRODUCTION: Fertility counselling for young women newly diagnosed with cancer is an important field of preconceptional counselling. This qualitative, small scale study explored how young women newly diagnosed with cancer experienced specialized fertility preservation counselling and treatment in the public Danish health care system. METHODS: Semi-structured, in-depth interviews were conducted with five women below 40 years recently diagnosed with cancer. All women received fertility counselling by a fertility specialist at the Fertility Clinic, University Hospital of Copenhagen, Denmark before initiation of cancer treatment. Participants were interviewed at a place chosen by them, and interviews were recorded and transcribed verbatim. Data were analysed using systematic text condensation developed by Malterud and inspired by Giorgi's phenomenological analysis. RESULTS: None of the participants were aware that chemotherapy could destroy their eggs. The participants described how specialized fertility counselling and fertility preservation contributed to a belief in life after cancer, which gave them hope that they would survive their cancer disease. Further, the women described how the possibility of fertility preservation removed a huge concern and enabled them to concentrate on their cancer treatment and on getting better. CONCLUSION: Overall, the specialized fertility counselling and treatment to preserve fertility was highly valued. The women felt it gave them a choice about their future fertility. The fertility expert presented the various fertility-preserving scenarios, and the women were content that they had an actual choice. PMID- 27413811 TI - Effects of social integration on depressive symptoms in Korea: analysis from the Korean Longitudinal Study of Aging (2006-12). AB - Objectives The effects of a range of types of social integration and patterns of change in social integration over time were examined directly in relation to depressive symptoms in a large sample of the Korean population aged >=45 years. Methods Data from the Korean Longitudinal Study of Aging (KLoSA) between 2006 and 2012 were assessed using longitudinal data analysis. We included 10242 research subjects at baseline (2006) and based the primary analysis on generalised linear mixed models to examine association between social integration and depressive symptom. Results The odds ratio (OR) for depressive symptoms in individuals at the lowest level of social integration was 1.539-fold higher (95% confidence interval (CI) 1.360-1.742) that that for those at highest level of social integration. Results of subgroup analysis according to gender revealed a similar trend. A five-class linear solution fit the data best; Class 1 (lowest constant social integration level, 10.5% of the sample) was significantly associated with the highest risk of depressive symptoms (OR 1.933, 95% CI 1.706-2.190). Conclusions The results of the present study provide a scientific basis for the specific association between the level of social integration and changes in social integration pattern with the risk of depressive symptoms in current practice. Therefore, interventions to provide emotional support for older adults via social integration may be important to protect against depressive symptoms. What is known about the topic? Although there has been considerable discussion about social integration among old adults, few studies related to effect of social integration on depression have been conducted. What does this paper add? The findings of the present study indicate that a high level of social integration is inversely related to depressive symptoms and is also associated with a substantial positive effect on depressive symptoms among individuals aged >=45 years. What are the implications for practitioners? This paper provides evidence showing that it is useful to assess indicators of both social and emotional loneliness, which have been theorised to correspond to low social integration. PMID- 27413813 TI - Broadband Phase-Sensitive Single InP Nanowire Photoconductive Terahertz Detectors. AB - Terahertz time-domain spectroscopy (THz-TDS) has emerged as a powerful tool for materials characterization and imaging. A trend toward size reduction, higher component integration, and performance improvement for advanced THz-TDS systems is of increasing interest. The use of single semiconducting nanowires for terahertz (THz) detection is a nascent field that has great potential to realize future highly integrated THz systems. In order to develop such components, optimized material optoelectronic properties and careful device design are necessary. Here, we present antenna-optimized photoconductive detectors based on single InP nanowires with superior properties of high carrier mobility (~1260 cm(2) V(-1) s(-1)) and low dark current (~10 pA), which exhibit excellent sensitivity and broadband performance. We demonstrate that these nanowire THz detectors can provide high quality time-domain spectra for materials characterization in a THz-TDS system, a critical step toward future application in advanced THz-TDS system with high spectral and spatial resolution. PMID- 27413814 TI - A case of TAFRO syndrome, a variant of multicentric Castleman's disease, successfully treated with corticosteroid and cyclosporine A. AB - We report a case of a 46-year-old woman with fever, pleural effusion, massive ascites, severe edema, hepatosplenomegaly, elevation of serum creatinine level, proteinuria, and severe thrombocytopenia. Her clinical features were compatible with TAFRO syndrome proposed as a variant of multicentric Castleman's disease, that is occasionally associated with poor prognosis. Treatment with corticosteroid improved her symptoms partially. However, thrombocytopenia, ascites, and edema persisted. The use of cyclosporine A successfully improved her condition, resulting in remission. PMID- 27413816 TI - Pleuritic Chest Pain in a 24-Year-Old Man with Crohn's Disease. PMID- 27413815 TI - Rethinking cholera pathogenesis- No longer all in the same "camp". PMID- 27413818 TI - We're Not Playing with Monopoly Money. PMID- 27413817 TI - Mapping is a prerequisite for elimination of filariasis and effective targeting of filarial 'hot spots'. AB - OBJECTIVE: This study was undertaken to determine the prevalence of filarial infection in the districts of Madhya Pradesh, which were classified as non endemic by the national program for control of filariasis. These districts showed evidence of clinical symptoms related to filariasis. To confirm the presence of filariasis, night blood surveys and entomological surveys were carried out to detect microfilaria in humans and filarial infection in vectors. MATERIALS AND METHODS: For microfilaria surveys, thick blood smears were prepared by taking 60 MUL of blood between 8.00 and 11.00 pm and examined under a microscope. Vectors Culex quinquefasciatus were dissected for the filarial infection from the affected villages of four non-endemic districts. RESULTS: Prevalence of microfilaria in the four districts ranged from 3.8% in district Shivpuri to 11.2% in district Bhind (overall mf rate 6.9%, 95% CI = 6.2-7.7). Infection and infectivity rates among vectors were recorded from three districts which varied from 2 to 13% and from 1.3 to 3.6%. CONCLUSION: The study confirmed the presence of circulating microfilaria in non-endemic population of four districts, which has significant public health implications. To assess filarial endemicity and hot spots, precise filarial risk mapping using new efficient diagnostic tools is needed to reinforce and extend the strategy in other areas to achieve elimination of lymphatic filariasis. PMID- 27413819 TI - Hospitals Need to Help Industry Keep Improving Healthcare Technology: Response to Pritchett. PMID- 27413820 TI - Increased Complexity Means Trickier Telemetry Problems: Response to Crossley. PMID- 27413821 TI - Increased Complexity Means Trickier Telemetry Problems: Response to Lashway. PMID- 27413824 TI - Ten Questions With ....Sue Schade. PMID- 27413826 TI - Ask George. PMID- 27413827 TI - Choosing Wisely: Trends and Strategies for Capital Planning and Procurement. PMID- 27413828 TI - Comparison of Automated versus Manual Programming of Infusion Pumps. PMID- 27413829 TI - Reflections on the Current State of Infusion Therapy. PMID- 27413830 TI - Emerging Trends in Healthcare Adoption of Wireless Body Area Networks. AB - Real-time personal health monitoring is gaining new ground with advances in wireless communications. Wireless body area networks (WBANs) provide a means for low-powered sensors, affixed either on the human body or in vivo, to communicate with each other and with external telecommunication networks. The healthcare benefits of WBANs include continuous monitoring of patient vitals, measuring postacute rehabilitation time, and improving quality of medical care provided in medical emergencies. This study sought to examine emerging trends in WBAN adoption in healthcare. To that end, a systematic literature survey was undertaken against the PubMed database. The search criteria focused on peer reviewed articles that contained the keywords "wireless body area network" and "healthcare" or "wireless body area network" and "health care." A comprehensive review of these articles was performed to identify adoption dimensions, including underlying technology framework, healthcare subdomain, and applicable lessons learned. This article benefits healthcare technology professionals by identifying gaps in implementation of current technology and highlighting opportunities for improving products and services. PMID- 27413831 TI - Career Choices: Finding the Right Fit for the Job. PMID- 27413832 TI - A Roundtable Discussion: Combating the Complex Challenge of Healthcare-Associated Infections. PMID- 27413833 TI - Excellence in Sterilization Is but One of STERIS's Many Goals, Says Chief. PMID- 27413834 TI - CSPD Department Wins Back Trust, Just in Time. PMID- 27413835 TI - An Introduction to CyberInsights, and a Confession. PMID- 27413838 TI - Accountability, Communication, and Documentation: Lessons Learned from a Young Biomed. PMID- 27413837 TI - Why Are There Too Few Imaging Engineers? PMID- 27413841 TI - The Ups and Downs of Sports. PMID- 27413840 TI - Use of natalizumab in multiple sclerosis: current perspectives. AB - INTRODUCTION: Natalizumab is an efficacious monoclonal antibody approved for use in relapsing-remitting multiple sclerosis (RRMS). Multiple studies have demonstrated reduced relapse rate, decreased disability progression and prolonged disease-free intervals with natalizumab use. However, natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), thus restricting its widespread use with populations at high risk for developing PML. Recently, the effect of natalizumab in secondary-progressive (SPMS) population has been explored. AREAS COVERED: This review highlights the pathophysiology behind disease progression in MS and summarizes various attributes of natalizumab including: its pharmacological properties and global economic impact, results of clinical efficacy studies, its role in SPMS, pregnancy and its adverse events profile including PML and discontinuation protocols. EXPERT OPINION: Despite an established role in reducing RRMS disease activity, natalizumab has found limited use in SPMS due to insufficient evidence of efficacy. Current disease-modifying therapies exert modest overall benefit in SPMS owing to its complex pathophysiology, higher prevalence of comorbidities and increased PML risk with age and lack of reliable outcome measures. Finding more appropriate MRI and clinical outcome measures is quintessential for designing future randomized trials and possibly exploring primary neuroprotective agents for treating SPMS. PMID- 27413843 TI - Scanning sports. PMID- 27413842 TI - Retired But Still a Physician. PMID- 27413845 TI - Sportsmedicine forum. AB - A Forum For Our Readers Sportsmedicine Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Sportsmedicine Forum, The Physician and Sportsmedicine, 4530 W 77th St, Minneapolis, MN 55435. PMID- 27413849 TI - Sportsmedicine wrap-up. PMID- 27413848 TI - Violence in Youth Hockey. PMID- 27413850 TI - Coming in sportsmedicine. PMID- 27413851 TI - Self-Treatment of Gynecomastia in Bodybuilders Who Use Anabolic Steroids. AB - In brief: Gynecomastia is a cruel irony for bodybuilders who use steroids in hope of perfecting their somatotype. These athletes and their advisers perpetuate locker-room theories about which drugs to use to avoid this widely acknowledged feminizing effect. This paper presents four case reports of bodybuilders whose self-administered drug programs resulted in gynecomastia. These examples illustrate treatment strategies bodybuilders have advocated for the prevention and self-treatment of gynecomastia, which include the use of tamoxifen, mesterolone, and human chorionic gonadotropin. In fact, the recommended treatment is complete cessation of drugs. By dispelling unfounded treatment methods, physicians might help to discourage these athletes from such drug use. PMID- 27413852 TI - Hands-On Sports Medicine Training for Residents. AB - In brief: Primary care sports medicine is a rapidly growing field of interest; however, there are relatively few training programs in this field. The author describes the development of a one-month training program at the University of California, Davis, Medical Center. The education strategies used in the program include clinical teaching (50%), on-the- field education (20%), experiential learning (20%), and didactic instruction (10%). The most innovative part of the program is the experiential learning component, through which students learn basic sports medicine skills by actively participating in sports, exercises, strength training, and a fitness program. PMID- 27413853 TI - Is Low-Impact Aerobic Dance an Effective Cardiovascular Workout? AB - In brief: Ten women performed four different aerobic dance routines in a randomized crossover study to evaluate energy expenditure. The routines consisted of the following combinations: low intensity, low impact; high intensity, low impact; low intensity, high impact; and high intensity, high impact. The women warmed up for five minutes, then did a 20-minute routine. Metabolic measures were monitored by means of open circuit spirometry and heart rates measured by ECG. Statistical analyses showed that for both high and low intensities, the high impact routines required a significantly greater energy expenditure, regardless of heart rate. Thus for low-impact dance to meet the minimum guidelines for exercise suggested by the American College of Sports Medicine, it should be performed at high intensity. PMID- 27413854 TI - Management of Surfing Injuries: A Plastic Surgeon's Viewpoint. AB - In brief: Physicians of all specialties are likely to treat surfing injuries as the sport increases in popularity and is done in nontraditional areas-such as in commercial aquatic parks. Articles in the medical literature suggest that head lacerations and nose fractures are the most common injuries; these usually occur when the surfboard strikes the surfer. This finding was supported in a survey of 55 plastic surgeons in San Diego County, who reported the number and kinds of surfing injuries they had treated over the past ten years. The survey results indicated that lacerations may be deeper than expected from their surface appearance, and that surfboard fragments are often driven into the wound if the board breaks. The author describes the techniques used to irrigate, debride, and close lacerations caused by surfboards. PMID- 27413855 TI - Body Checking in Pee Wee Hockey. AB - In brief: Two separate studies were done to determine the effects of body checking at the Pee Wee level. Study 1 evaluated eight of the smallest and eight of the largest players from leagues that allowed body checking. The players were measured for height, weight, grip strength, maximal skating speed, impact force during a body check, and speed of skating at impact. Significant morphologic differences (p <.05) between small and large players were reflected in forces of impact. Study 2 investigated the incidence and types of injuries sustained among players competing in leagues with body checking and without. In the checking leagues 55.5% of all injuries were due to body contacts, and serious injuries occurred six times more often than in nonchecking leagues. In addition, body checking accounted for 88% of the 25 fractures recorded during one hockey season. PMID- 27413856 TI - Women in the Military Academies: US Air Force Academy (Part 2 of 3). AB - In brief: Since women entered the US Air Force Academy in 1976, their fitness level has continued to improve at an impressive rate. For example, at first they averaged seven fewer sit-ups than men; now the opposite is true-men average seven fewer sit-ups than women. The curriculum has remained virtually the same for both sexes. The physical fitness test is also the same for both men and women; the standards for the cardiovascular fitness test are slightly lower for women. A major concern is the women's injury rate, which is approximately twice that of men performing similar activities. The author stresses the need to identify factors contributing to the cause of this problem. (Physical fitness training at the US Naval Academy was discussed in part 1, February 1989.). PMID- 27413857 TI - Does Running Cause Osteoarthritis? AB - In brief: This review of the literature on exercise and arthritis considers the relevant epidemiologic and experimental studies of animals and humans, with a focus on the relationship between running and osteoarthritis. The cause of osteoarthritis-the most common joint disease in the United States-remains unknown. The incidence of the disease increases with age and eventually afflicts most people-athletes and nonathletes alike-to some extent: Almost everyone has some pathologic abnormality in the weight-bearing joints by age 40 or 50; by age 75 at least 85% of all people have diagnosable osteoarthritis. However, there is no conclusive evidence that running causes the disease; in fact, running may actually slow the functional aspects of musculoskeletal aging. PMID- 27413858 TI - Does Running Cause Osteoarthritis? AB - In brief: This article discusses the development of osteoarthritis and the question of whether running and other impact-loading sports promote osteoarthritis. Although participating in these activities does not cause arthritis in normal weight-bearing joints, it can accelerate the disease in damaged joints. The authors emphasize the importance of identifying persons with preexisting joint disease before they start an aerobic exercise program so they can select non-impact-loading exercise. Recommended exercise includes stationary cycling 20 to 30 minutes per day (making sure the seat is adjusted to the appropriate height) and weight training to maximize muscle strength to support the joints. Persons with no evidence of joint abnormalities can exercise without fear of the development of osteoarthritis. PMID- 27413859 TI - Preventing Cauliflower Ear With a Modified Tie-Through Technique. AB - In brief: Hematoma following trauma to the external ear is a common problem among wrestlers and boxers. If the hematoma is not treated promptly, infection, fibrosis, scarring, and calcification may develop, leading to the gross deformity known as cauliflower ear or wrestler's ear. Evacuation of the hematoma followed by compression of the auricle is commonly regarded as the treatment of choice. However, fluid frequently reaccumulates after this procedure. The authors describe a tie-through suture technique in which a collodion packing is secured to the auricle with two buttons. Multiple treatments for fluid reaccumulation are rarely necessary when this technique is used. PMID- 27413860 TI - Injury Patterns in Youth Sports. AB - In brief: Millions of US children participate in recreational activities, organized youth leagues, and interscholastic sports programs. Although they enjoy and obtain health benefits from these activities, 3% to 11% of these children are injured while participating in sports programs each year. Epidemiologic studies show that different sports pose different types and degrees of risk and that injuries among children differ from those among adolescents. An awareness of injury patterns in youth sports helps physicians and others who care for children to identify variables associated with injury. Measures must be taken in all youth sports programs to modify such variables in an effort to prevent injuries. PMID- 27413861 TI - Strength Training Guidelines for Cardiac Patients. AB - In brief: Many cardiac patients would like to improve their muscle fitness through a program of strength training. Evidence now indicates that such a program, if conducted within a medically supervised rehabilitation program, is both safe and beneficial. This article provides practical guidelines for a strength training program, which may be modified to fit a particular program. The recommendations include criteria for admission, procedures for orientation and instruction, and techniques for supervision. PMID- 27413862 TI - Chronic Pain and Exercise Therapy. AB - In the past, patients with chronic pain were told to limit their activity and shield themselves from pain. But that has changed: Physicians now prescribe both aerobic and resistance exercise to treat chronic pain. PMID- 27413863 TI - Sunlight and Cataracts: Are Athletes at Risk? AB - People who spend a lot of time outdoors face an increased risk of developing cataracts, a recent study suggests. Authorities say the evidence is strong enough to warrant recommending protective lenses for outdoor athletes, especially those involved in winter sports. PMID- 27413864 TI - In Pro Hockey, Getting Out May Be Smarter Than Playing Hurt. AB - After four seasons of playing with multiple injuries, professional hockey star Craig Hartsburg had two choices: He could hang up his skates, or he could continue playing and risk incurring serious handicaps and a painful future. PMID- 27413866 TI - How Healthy Are Corporate Fitness Programs? AB - Many US companies offer health promotion programs to their employees. Despite a lack of research on whether the programs actually help improve employee fitness or reduce health care costs, it appears that corporations may consider physical fitness to be an important component of fiscal fitness. PMID- 27413865 TI - Reemphasizing the Role of Exercise in Preventing Heart Disease. AB - New studies suggest that high-density lipoprotein cholesterol (HDL-C) may be a better predictor of heart disease than is total cholesterol. Physicians evaluating that evidence stress that even moderate amounts of aerobic exercise can raise HDL-C-and lower the risk of coronary artery disease. PMID- 27413867 TI - Questioning the Athlete's Right to Sue. AB - The once-common doctrine that an athlete assumes the risks of the sport in which he or she competes almost disappeared in the 1970s. In the following interview, legal expert Gerald J. Todaro, JD, questions an athlete's right to sue for an injury that occurred in an inherently dangerous sport. PMID- 27413868 TI - People and Horses: The Risks of Riding. AB - Horseback riding carries several risks, some of which can be minimized if riders take riding lessons, wear proper headgear and footgear, and remember that they are on top of a large, willful animal. PMID- 27413869 TI - Is Weight Training Safe During Pregnancy? AB - There has been no definitive research on the safety of weight training during pregnancy. Nevertheless, several experts seem to agree that low-intensity weight training probably poses no harm for either the fetus or the mother. PMID- 27413871 TI - Low-Impact Aerobics. PMID- 27413872 TI - Nanocapillary Adhesion between Parallel Plates. AB - Molecular dynamics simulations are used to study capillary adhesion from a nanometer scale liquid bridge between two parallel flat solid surfaces. The capillary force, Fcap, and the meniscus shape of the bridge are computed as the separation between the solid surfaces, h, is varied. Macroscopic theory predicts the meniscus shape and the contribution of liquid/vapor interfacial tension to Fcap quite accurately for separations as small as two or three molecular diameters (1-2 nm). However, the total capillary force differs in sign and magnitude from macroscopic theory for h ? 5 nm (8-10 diameters) because of molecular layering that is not included in macroscopic theory. For these small separations, the pressure tensor in the fluid becomes anisotropic. The components in the plane of the surface vary smoothly and are consistent with theory based on the macroscopic surface tension. Capillary adhesion is affected by only the perpendicular component, which has strong oscillations as the molecular layering changes. PMID- 27413874 TI - Summary Self-Test. PMID- 27413873 TI - Introduction. PMID- 27413876 TI - Ready Source on Hypertension. PMID- 27413875 TI - Clinical Outlines. PMID- 27413878 TI - Therapeutic Index to Advertisers. PMID- 27413877 TI - A Pamphlet for Patients. PMID- 27413879 TI - Chronic Myeloid Leukemia: Current Guidelines for Diagnosis and Management. AB - Over the past two decades advances in the understanding of molecular and biological aspects of chronic myeloid leukemia (CML) have served as one of the cornerstones of progress in the management of leukemias, and more broadly of cancer in general. With the identification of the Philadelphia chromosome and its association with 95% of cases of CML and later with the possible etiologic role of the BCR-ABL fusion gene in the initiation of CML, a new chapter in the understanding of leukemogenesis was entered upon. Later with the identification of interferons as a therapeutic modality, and demonstration of their role in suppression of the malignant clone and the associated increase in survival, CML was one of the first malignancies in which biologic therapy found an established role. With advances in allogeneic bone marrow transplantation, it is hoped that more patients would be able to benefit from this curative therapy with less associated toxicity. However, a large proportion of patients are still unable to undergo an allogeneic transplant due to lack of donors and the expected toxicity. Other therapeutic modalities including new forms of interferon, new agents such as Homoharringtonine, and new techniques such as purged autologous transplant with or without immuno-modulation need to be further developed and perfected. Our current challenges are to stratify CML patients, using the available risk scores in order to assign the most appropriate therapy to the individual, and to continue to improve upon the available therapies. PMID- 27413880 TI - Clinical Regression and Remission of Primary Refractory Angiocentric Lymphoma Following Autologous Tumour Peptide Antigen-charged Dendritic Cells After High dose Chemotherapy and Autologous Stem Cell Rescue. AB - We report on the case of a 34-year old man with a previously refractory high grade non-Hodgkin's Lymphoma which regressed following dendritic cell based immunotherapy after high-dose chemotherapy. Antigen presenting cells known as dendritic cells were cultured from harvested autologous peripheral blood progenitor cells. The dendritic cells were then exposed to unfractionated tumour peptides derived from a skin biopsy section inflitrated with lymphoma. These charged dendritic cells infused into the patient together with autologous T lymphocytes after high-dose chemotherapy with peripheral blood stem cell rescue. Although the lymphoma relapsed after the high-dose chemotherapy it regressed again following the dendritic cell infusion. The patient's T-lymphocytes demonstrated in vitro reactivity to tumour peptides whereas the lymphocytes of controls did not. We propose that the lymphoma regression occurred because of a T cell mediated response against the tumour induced by the charged dendritic cells. PMID- 27413881 TI - Use of Bisphosphonates in the Treatment of Multiple Myeloma. AB - Bone pain is the single most common presenting complaint in myeloma. Although first-line chemotherapy has a marked effect on bone pain, skeletal disease frequently continues to progress throughout the course of the disease and the incidence of skeletal events remains high. The underlying pathology in myeloma constitutes mainly increased osteoclastic activity but also reduced osteoblastic activity. Any agent that inhibits osteoclast activity potentially provides some degree of skeletal protection although only the bisphosphonates have achieved widespread use. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and evidence of bone protection and modification of skeletal disease progression has been greatest with clodronate and pamidronate. The MRC VIth Myeloma Trial is, to date, by far the largest randomised placebo-controlled trial of bisphosphonates in myeloma. Current evidence suggests that bisphosphonate treatment should begin as early as possible and continue indefinitely, and probably should be considered for all patients with myeloma. The additional costs of clodronate therapy in the management of myeloma patients were around 17% higher than in controls which is moderate when considering the significant reductions in hypercalcaemic episodes and in vertebral and non-vertebral fractures. PMID- 27413882 TI - Refractory Castleman's Disease. AB - Angiofollicular lymph node hyperplasia is an uncommon low-grade lymphoproliferative disorder first described by Castleman. It is typically asymptomatic with diagnosis incidentally made in young males on chest radiology. Biopsy, in 90% of cases, shows the hyaline vascular variant. In contrast the plasma cell sub-type is accompanied by fever, sweating, weight loss, anaemia, lymphadenopathy, splenomegaly and hypergammaglobulinaemia. Treatment, when necessary because of symptoms, has variable outcome in response to corticosteroids, combinations of cytotoxic drugs, or radiotherapy. Failure to promptly achieve disease control has ominous significance and most patients die. High-dose chemoradiotherapy with bone marrow salvage, using haematopoietic stem and progenitor cells derived from bone marrow or peripheral blood, has precedent in this situation. We report a second successful outcome to this procedure in a 37 year old man with profound constitutional complaints of weight loss, drenching sweats, relentless high fevers and massive organomegaly, resistant to all previous therapy. After conditioning with total body irradiation, cyclophosphamide and high-dose melphalan followed by total nodal irradiation, he underwent peripheral blood stem cell allograft from an HLA-compatible sister. Despite his course being complicated by pulmonary tuberculosis he achieved immediate complete remission, and restaging at one year confirms this to be durable. This further anecdotal case report supports this option in refractory aggressive variants of this disease. PMID- 27413883 TI - The Syndrome of Veno-occlusive Disease After Blood or Marrow Transplantation. AB - Veno-occlusive disease of the liver (VOD) was originally described in patients who drank infusions made with plants containing pyrrolizidine alkaloids [1]. This disease was characterized, histologically, by a progressive and concentric non thrombotic narrowing of the lumina of small intrahepatic veins. Later, VOD was related to other pathogens such as alcohol, contraceptives, toxic oil, liver radiation and several antineoplastic drugs [2-3]. The first case of veno occlusive disease following bone marrow transplantation (BMT) was reported in 1979 [4]. Since then, BMT has proved to be the main cause of VOD which is one of the leading causes of morbidity and mortality after transplant [5-7]. Clinical manifestations of VOD are very characteristic (jaundice, painful hepatomegaly and fluid retention) but indistinguishable from those produced by other regime related morphological changes on zone 3 of the liver acinus. For this reason, the term "syndrome of veno-occlusive disease of the liver" has been adopted to designate the clinical manifestations of conditioning regimen toxicity on this zone [8]. This review focuses on the present knowledge of VOD syndrome after BMT. PMID- 27413884 TI - Respiratory Failure and Intensive Care Support Following Bone Marrow Transplantation. AB - Recipients of allogeneic bone marrow transplantation frequently develop life threatening complications, which require intensive care management. The reported prognosis of bone marrow transplant (BMT) recipients who require admission to the intensive care unit (ICU) is poor [1], We retrospectively examined the records of 25 BMT patients at our centre who required ICU admission between January 1989 and May 1997. Respiratory failure was the most frequent reason for admission. Twenty five patients required ventilation and two of these survived. Fifteen patients were investigated at an early stage using bronchoscopy. Fifteen patients had bronchoalveolar lavage (BAL) and 8 had transbronchial biopsies (TBB). Despite positive findings in 5 BAL and 3 TBB and an appropriate change in treatment, none of these patients survived. In spite of early investigation and intensive support the prognosis of patients with severe respiratory failure after BMT remains poor. Early investigation with bronchoscopy provides a diagnosis in 50% of cases although we are unable to demonstrate a survival advantage in this group of patients. PMID- 27413885 TI - European Concerted Action on Anticoagulation (ECAA): Clinical and Laboratory Studies. AB - The European Concerted Action on Anticoagulation has been concerned over its first 4 years with both clinical and laboratory aspects of oral anticoagulation in 16 European states. A number of relevant reports have been published which are summarised. In a clinical study from 5 centres with no previous experience of computer dosage a randomised multicentre investigation of a computer dosage program has demonstrated the significant benefit from a computer dosage program compared to traditional (manual) dosage by experienced medical staff. Not only was there greater success in achieving the target INR intervals, but less dose adjustment with the computerised program. The benefit of computer dosage which is widely available, may be even greater at less specialised centres or where there is less interest in anticoagulant dose administration. Laboratory studies have been principally with the assessment of the value of lyophilized plasmas in local ISI calibration. Lyophilized plasmas have been used because their use avoids the necessity for the discarded manual PT technique and the provision of thromboplastin reference preparations. Both lyophilized artificially depleted and coumarin plasmas were shown to give acceptable ISI in ECAA multicentre studies. They differed from the fresh plasma ISI by a measurable but clinically acceptable amount. The two types of lyophilized plasma differed from each other to a greater degree. A minimum of 20 artificially depleted with 7 normal plasmas was required for reliable calibration with a low ISI reagent. For fresh plasma calibrations the current WHO recommendation of 60 fresh coumarin and 20 normal plasmas is substantiated by the ECAA studies. Lyophilized plasmas should be used only for "like-to-like" calibrations. Lyophilized normal plasmas cannot reliably replace the fresh plasma MNPT as they give prolonged results with low ISI thromboplastins. Where coagulometers disturb ISI, local INR correction with certified artificially depleted plasmas is advantageous and considerably increases inter-laboratory precision. Linear regression analysis in place of orthogonal regression does not appear advisable for local coagulometer ISI calibration. PMID- 27413886 TI - Estimation of the Infectious Risks of Blood Transfusion. AB - Despite the success of efforts made to prevent the transmission of infections by blood transfusion, the risk of infectious donations entering the blood supply and transmitting infection to the recipients of blood components and blood products remains a concern. Following the implementation of donor selection and donation testing strategies to exclude HBV, HIV, and HCV infectious donations from the blood supply, direct observation of transmission of these viruses by blood transfusion has become rare and indirect estimation of the probable frequency of infectious donations entering the blood supply has become more common. Published estimates for different blood services and different periods of time have varied in their methods and scope. The limitations of the estimation process should be considered when using estimates of the risk of infectious donations entering the blood supply to address questions about blood safety. PMID- 27413887 TI - Green dyeing process of modified cotton fibres using natural dyes extracted from Tamarix aphylla (L.) Karst. leaves. AB - This research work involves an eco-friendly dyeing process of modified cotton with the aqueous extract of Tamarix aphylla leaves. During this process, the dyeing step was carried out on modified cotton by several cationising agents in order to improve its dyeability. The influence of the main dyeing conditions (dye bath pH, dyeing time, dyeing temperature, salt addition) on the performances of this dyeing process were studied. The dyeing performances of this process were appreciated by measuring the colour yield (K/S) and the fastness properties of the dyed samples. The effect of mordant type with different mordanting methods on dyeing quality was also studied. The results showed that mordanting gave deeper shades and enhanced fastness properties. In addition, environmental indicators (BOD5, COD and COD/BOD5) were used to describe potential improvements in the biodegradability of the dyebath wastewater. Further, HPLC was used to identify the major phenolic compounds in the extracted dye. PMID- 27413889 TI - Bright lights. AB - If you're tempted by the capital's bright lights, finding a post in nursing should present very few difficulties. PMID- 27413890 TI - Soaring to new heights. AB - Historic news on the reform of nurse education last week with the I Health Secretary's announcement of the Government's acceptance of the key recommendations contained in Project 2000. PMID- 27413888 TI - JAGGER, an AGP essential for persistent synergid degeneration and polytubey block in Arabidopsis. AB - A precise control of sperm cells delivery and fusion to the egg cell and the central cell is fundamental for the accomplishment of successful double fertilization in flowering plants. This is mostly regulated by female gametophyte egg and central cells, which control the timing of synergids cell degeneration. We recently identified an arabinogalactan protein, AGP4, named JAGGER, that impairs the persistent synergid degeneration, and consequently leads to the attraction of more than one pollen tube into one embryo sac, a situation termed polytubey. jagger mutants revealed an increased rate of polytubey and persistent synergids that do not degenerate. This persistent synergid, is, as we suggested, the cell responsible for attracting an extra pollen tube into the embryo sacs. PMID- 27413892 TI - ? AB - Over a hundred delegates queued to speak on a motion at last week's RCN Congress calling for direct elections to the United Kingdom Central Council. Strong opposition for the resolution, which was lost, came from delegates from Scotland, Wales and Northern Ireland who felt their regions would lose out on representation. PMID- 27413891 TI - Call for free hepatitis B vaccination for staff. AB - Royal College of Nursing members have called for free vaccination against hepatitis B for all staff at risk. PMID- 27413894 TI - No Reductions in Number of Qualified Staff. AB - RCN membership fired its first warning shot over the Government's implementation of Project 2000 when it unanimously resolved to oppose any reductions in the number of qualified nursing staff. PMID- 27413893 TI - Associate membership taken on board. AB - The possibility of nursing assistants becoming associate members of the Royal College of Nursing is to be taken on board by RCN Council. PMID- 27413895 TI - Fear of Inadequate Funds. AB - Enrolled nurses are afraid that adequate funding will not be given for the development of conversion courses despite Government support for Project 2000. Val Rushton of the Royal College of Nursing Association of Nursing Practice commented, 'We still do not know when enrolled nurse training is going to cease. No date has been given.' PMID- 27413896 TI - Discussion on NHS review. AB - Labour Health spokesman Robin Cook has welcomed the Government's acceptance of the Project 2000 proposals and has called for similar consultation with the nursing profession throughout the Government review of the NHS. PMID- 27413897 TI - Unlucky Lottery Declared 'unlawful'. AB - The national lottery designed to provide the Health Service with extra cash was declared 'unlawful' last week, minutes before it was due to be drawn. PMID- 27413898 TI - Closer ties with private sector. AB - A majority of unit general managers want more co-operation with the private health sector, according to a survey commissioned by BUPA. PMID- 27413899 TI - Upset Over Delay. AB - Disappointment at Government delay in implementing proposals from Project 2000 until further work related to manpower requirements is undertaken has been expressed by Professor Christine Chapman, Chairman of the Welsh National Board. PMID- 27413900 TI - Protecting the rights of the elderly. AB - Health visitors are to urge the Government to formulate a Bill of Rights for elderly people in the NHS, after a unanimous vote at their annual general meeting. PMID- 27413901 TI - Storm brewing over support workers' pay. AB - The National Health Service is set for more industrial trouble after 225,000 hospital support workers demanded urgent action to improve their pay. PMID- 27413903 TI - In the event of a nuclear accident... AB - Government advice to health authorities in the event of a nuclear accident is to be released shortly. The Department of Health circular detailing the health service response to an accident was expected earlier this year, but is now in 'an advanced stage of preparation,' according to a DHSS spokeswoman. PMID- 27413904 TI - Sir roy chides too sensitive' nurses. AB - Sir Roy Griffiths angered nurses last week when he told them not to be 'too sensitive' because they were not mentioned on every page of his review of community care. PMID- 27413905 TI - Support for random breath tests. AB - Members of the Royal College of Nursing have given their support in calling for the introduction of random breath testing for motorists. During a debate at last week's annual Congress, delegates heard details of alarming statistics. In 1986, 50 [Illegible word] of fatal accidents involved [Illegible word]hol in either the victim or the driver. One Accident and Emergency nurse said that around 7,700 passengers a year are involved in accidents connected with drink driving, along with 1,200 pedestrians. PMID- 27413907 TI - Close Shave for YTS. AB - The controversy surrounding the use of Youth Training Scheme workers in the National Health Service was clearly reflected when a resolution was defeated on a card vote with only a 14 vote margin. PMID- 27413906 TI - Pregnant women HIV test slammed. AB - The Royal College of Midwives has slammed Government plans to test more than 90,000 pregnant women for HIV, claiming it is 'morally wrong' and exploitative to request women in antenatal clinics to take part, in any surveillance plan. PMID- 27413908 TI - Family planning in today's society. AB - Congress endorsed the view' of the Family Planning Nurses Forum that an urgent review of the work, role and function of family planning clinics is needed. PMID- 27413909 TI - Independent counselling for nurses under stress. AB - A resolution that health authorities should provide independent counselling services for nurses under stress was overwhelmingly supported. PMID- 27413910 TI - More resources for NHS. AB - The Government is to be urged to direct a greater proportion of national resources towards the National Health Service, and allocate a further L 1.5 billion to it. PMID- 27413912 TI - Change of attitude needed over recruitment. AB - Attitudes of nurses, teachers and careers advisers must change if the serious problems of recruitment into the nursing profession are to be addressed. PMID- 27413911 TI - Concern over Maintaining Community Care. AB - Congress expressed its serious concern about the lack of adequate funding to maintain community care following the closure of mental illness and mental handicap hospitals. PMID- 27413913 TI - Government urged to reconsider dhss changes. AB - The Government's Social Security policy was branded as a 'criminal act of negligence' by Jenny Feed, of the Bristol Branch, when she proposed the resolution requesting Council to consider urgently the adverse effects that changes in social security regulations will have. PMID- 27413914 TI - Renal dialysis units for wales. AB - Patients living in rural areas in south Wales who have to rely on renal dialysis will benefit from the next stage in the Welsh Office's scheme to provide them with facilities closer to home. PMID- 27413915 TI - MacClesfield centre praised. AB - Developments in the care of people with a mental handicap in Mersey region have been highly praised as 'interesting and innovative' by the Mental Health Act Commission. The Commissioners were so impressed by the programme at Macclesfield that it will feature as a centre of good practice in the next Commission report. PMID- 27413916 TI - ? AB - Fourth year student nurse tmma Moore accepts a high-powered boost to the Great Ormond Street Wishing Well Appeal. The new Escort donated by Ford Motor Company Limited will be raffled by the Hospital's nurses during their rag week in August. Proceeds from the raffle will be added to the L25 million appeal fund. PMID- 27413917 TI - Opposition to ward closure in tyneside. AB - Plans to close a geriatric rehabilitation ward at Preston Hospital in North Tyneside have met with strong opposition from nurses. The closure is part of a cost cutting exercise in an attempt by the health authority to remedy a L500,000 budget deficit in this financial year. PMID- 27413918 TI - Hammersmith hospital development completed. AB - The first part of an L18.5 million development programme at Hammersmith Hospital in London opens this week with the move of satellite outpatient facilities into a brand new central base. Nursing staff took part in a massive transfer exercise and the Hospital's Commissioning Officer, Philip Yelland, described the move as 'certainly the biggest upheaval the Hospital has faced since it was built in 1906'. PMID- 27413919 TI - Diet in a scottish town. AB - Health care professionals in Inverurie, near Aberdeen in Scotland, are to embark on a dietary survey of 12,000 people. PMID- 27413921 TI - Cutting Mersey Waiting Lists. AB - Mersey Regional Health Authority hopes to cut its waiting lists by treating an additional 8,200 patients this year. PMID- 27413920 TI - Joint management group for ISLE of wight. AB - Caring for mentally handicapped people in the community is w the joint responsibility of Health and Social Service bodies on the Isle of Wight. PMID- 27413922 TI - East Surrey Recruitment Drive. AB - East Surrey HA has launched a retraining and recruitment campaign in an effort to fill vacancies for 500 health staff. PMID- 27413923 TI - Marathon effort for london cancer fund. AB - A relay marathon could raise L250,000 for the Royal Marsden Hospital Cancer Fund if the sponsors attract 100 teams of 11 runners to take part in the new event. PMID- 27413924 TI - Opposition to harlow hospital. AB - A L30 million scheme to redevelop the Princess Alexandra Hospital in Harlow is being opposed by local residents and nurses, who fear that the journey of up to 40 miles from outlying areas could be fatal for some patients. PMID- 27413925 TI - Tenth birthday of the oncology society. AB - The Royal College of Nursing Oncology' Society celebrated its tenth birthday this year at the Congress in Brighton. PMID- 27413926 TI - Health care for the homeless. AB - Community nursing services have a key role in enabling homeless people to enjoy the same right to health care as other citizens, say the organisers of an important conference to be jointly staged by the RCN and CHAR, the housing campaign for single people. PMID- 27413927 TI - President Receives Award. AB - Maude Storey, President of the Royal College of Nursing, pictured receiving the Most Venerable Order of the Hospital of St John of Jerusalem at an investiture ceremony held in the Grand Priory Church in London recently. The Order of St John honours men and women for their services to mankind and as Sovereign Head of the Order, Her Majesty the Queen approves each award. PMID- 27413929 TI - Lighting the Way in Canada. AB - One of Britain's leading nurse historians Dr Monica Baly has been invited to visit Canada to deliver a keynote address at a major conference on Florence Nightingale and her legacy. PMID- 27413928 TI - Information on conversion courses and clinical grading areas. AB - A new leaflet giving enrolled nurses the latest information on conversion courses and clinical grading areas has been produced by the RCN. PMID- 27413931 TI - Fund for Stoma Research. AB - Nurses involved in stoma care, incontinence or wound management are set to receive extra support with the launch of a new charity to fund research and an information service. PMID- 27413930 TI - Nurse researchers should attend the real world. AB - Nurse researchers should investigate problems that arise from the real world, rather than pursue 'answers to questions that nobody cares about', according to distinguished nurse researcher, Elizabeth Hockey. PMID- 27413933 TI - Moving heads can cause damage. AB - Nurses should avoid moving head-injured patients unnecessarily because of the risk of causing secondary brain damage, according to research from Oxford. PMID- 27413934 TI - The need to know about vitamins. AB - A 24-hour vitamin information service designed to serve the needs of health care professionals was launched last week by the pharmaceutical company Roche. The service will be advised by an independent group of experts who will produce updates, leaflets, posters and audio-visual aids for health care professionals. PMID- 27413935 TI - Taking action on research. AB - Progressive and far reaching changes in ward practice can be made by actively involving staff in research projects, the Bloomsbury Research Interest Group heard last week. PMID- 27413936 TI - Learning pack on epilepsy. AB - Nurses and health educationalists at the National Society for Epilepsy are updating their nurse education package. PMID- 27413937 TI - Alcohol free beer link with strokes. AB - Doctors warned last week that people taking monoamine oxidase inhibitors (MAOIs) could be at risk of stroke if they drink alcohol free beer. PMID- 27413938 TI - High blood pressure in northern men. AB - The incidence of high blood pressure - which increases the risk of heart attacks varies with geographic location, research showed last week. PMID- 27413939 TI - Lipids - and the company they keep. AB - Blood lipid measurements are of value in predicting those at risk of coronary heart disease only when they are used alongside other risk factors, according to Geoffrey Rose, Professor of Epidemiology at the London School of Tropical Medicine and Hygiene. PMID- 27413940 TI - Women's health and alcohol. AB - Teetotal women are less likely to develop breast cancer than women who drink, according to research from America. PMID- 27413941 TI - Importance of team approach stressed. AB - Coronary heart disease prevention programmes in general practice can only work if they use a team approach, according to John Hosier, GP and lecturer in General Practice, Oxford University. PMID- 27413943 TI - Dhss to make changes to drug tariff. AB - The Department of Health and Social Security is this week expected to make firm changes to the Drug Tariff that will allow general practitioners to prescribe blood glucose testing strips. PMID- 27413942 TI - New guidelines on midwifery practice. AB - The Royal College of Midwives has responded to members' worries about Department of Health Guidelines on breastfeeding and HIV infection by producing its own guidelines. PMID- 27413944 TI - New drugs act on blood clot. AB - Thrombolysis in acute myocardial infarction is receiving world-wide attention. Recently a team of cardiologists met with specialist nurses and doctors to review their use. PMID- 27413945 TI - Booklet defines the nurse specialist. AB - The Royal College of Nursing has tackled the thorny issue of defining the nurse specialist by means of a newly-published . booklet. PMID- 27413946 TI - Baby milk code is being ignored. AB - Health professionals are still handing out free samples of baby milk formulae to mothers before they leave hospital - despite clear guidance to the contrary, according to a new report. PMID- 27413947 TI - Calling time. AB - Changes in the licensing laws should take account of the times at which alcohol related road accidents occur, according to a study from Dundee. PMID- 27413948 TI - Pollen sensitivity. AB - A highly specific test for sensitivity to pollen could soon be developed. PMID- 27413950 TI - Salad poisoning. AB - Prepackaged salads may be a source of Listeria monocytogenes food poisoning. PMID- 27413949 TI - Student depression. AB - A majority of nursing students suffer depressive symptoms, an increase in burnout and frequency of alcohol use during their educational years. PMID- 27413951 TI - Cancer functioning. AB - Predicting cancer patients' functioning following a course of radiotherapy may be best achieved by measuring their tension-anxiety at the beginning of treatment, according to research from Toronto. PMID- 27413952 TI - Information exchange. AB - We are a group of nurses collecting information for a project entitled 'Coping with the Elderly Confused/ Aggressive Patient at Night'. PMID- 27413953 TI - Readers' postscripts. AB - 'Thank you for your Watchdog page which I read with interest. This week I feel I may be able to shed some light on Robinow Syndrome for you....' PMID- 27413954 TI - Watchdog. AB - QI am almost 16 years old and would like to train to be a nurse. I sit my GCSE (General Certificate of Secondary Education) exams in late June this year. I have applied for a place in a technical college for a pre-nursing course. PMID- 27413955 TI - Radical intervention. AB - Call me thoughtful and committed with a sense of humour,' said F; Jane Salvage drily as the photographer clicked away. Though she probably never imagined this tongue-in-cheek but modest aside would be used to describe her, it fits pretty accurately. PMID- 27413956 TI - Clinical Pharmacology for Nurses Clinical Pharmacology for Nurses Trounce J et al Churchill Livingstone 12th edition 298pp L8.95 0-443-3581-4 [Formula: see text]. AB - The twelfth edition of Professor Trounce's popular pharmacology book for nurses appears in a new format, uniform in size with Churchill Livingstone's other nursing texts. The larger page and modern print in two columns makes for easier reading - especidi; when tired. Diagrams [illegible word] tables can also be bigger, increasing clarity. PMID- 27413957 TI - Being there Being there Published by SPCK/Sheldon 164pp L4.95 0-281-04325-6 [Formula: see text]. AB - Peter Speck writes both informatively and practically concerning the issues involved in pastoral care and visiting the sick. Being There provides a valuable insight from an aspect often forgotten on the wards - the visitor's view of things. He covers psychological, spiritual and practical matters based on his experiences as a hospital chaplain. PMID- 27413958 TI - Community nursing management of patients with ulcerating/fungating malignant breast disease Community nursing management of patients with ulcerating/fungating malignant breast disease Sims R and Fitzgerald V Published by the RCN/Scutari 32pp L1.85 +p&p 1-870687-15-9 [Formula: see text]. AB - Ruth Sims and Valerie Fitzgerald offer a short but comprehensive appraisal of a most sensitive area of wound management. Currently, literature specific to the care of patients with malignant ulcerating breast disease is sparse, but here the authors give community nurses in particular, a concise compilation and criticism of current practices, ideas and products. PMID- 27413960 TI - More money to aid welsh waiting list cuts. AB - An extra L1 million has been ear-marked for cutting hospital waiting lists in Wales. PMID- 27413959 TI - Personal data protection in health and social services Personal data protection in health and social services Pearce P et al Croom Helm 134pp L8.95 0-7099-3681-8 [Formula: see text]. AB - The Data Protection Act, of all the Acts of Parliament that have been placed upon the Statute book in recent years is, arguably, likely to have the most profound effect upon the day-to-day work of nurses. It is true to say that the full impact of the Data Protection Act is yet to be experienced, but it is essential that its implications are understood. PMID- 27413961 TI - Infant mortality rate is dropping slowly. AB - Baby death rates are coming down again ... but not as fast as hoped. PMID- 27413962 TI - Call for more psychiatric nurses. AB - Big increases in the number of community psychiatric nurses being trained have been called for in the Commons amid fears of a future shortage. PMID- 27413963 TI - Abortion bill on ice. AB - The parliamentary battle over the Alton Bill - aimed at cutting abortion time limits from 23 to 18 weeks - has been shelved for a month. It follows the unorthodox attempt by anti-abortion MP David Alton and his supporters to keep the measure alive by tacking it to the Government's own legislation. PMID- 27413965 TI - Smoke free commons. AB - The House of Commons is considering calls to make it a 'smoke free' zone. PMID- 27413964 TI - Celebrating 40 years of the NHS. AB - Health Secretary John Moore plans to mark the 40th anniversary of the NHS with a few drinks with NHS workers. PMID- 27413966 TI - Confidence booster. AB - I am a 36 year old registered general nurse, who has worked on a hospital ward since 1978. I am at present nearing the end of a 'Back to nursing' course. I have had time away from work to bring up my daughter, and now I am able to return to part time work, but feel I am not confident enough to be in charge of a ward. PMID- 27413967 TI - Cease fire. AB - I am saddened by the correspondence concerning the relevant merits of district and practice nurses precipitated by the letter by Yvonne Salisbury (Nursing Standard week ending May 14, 1988). We have waited so long for a clinical career structure for nurses. Must we now start an endless wrangle about who is more worthy than whom? Surely the most important issue is to ensure a just recognition of each person's skill and experience. PMID- 27413969 TI - Celebration. AB - The Association of Nurse Education is celebrating a day in which many of the aspirations of nurse education campaigners over 50 years have been fulfilled. PMID- 27413968 TI - Monitoring implementation. AB - The Association of Nursing Practice welcomes the statements on Project 2000 and shares John Moore's concern regarding staffing levels during implementation. But clinical nurses feel that the present situation with students being inadequately supervised cannot continue. PMID- 27413970 TI - Pioneering interest group. AB - Having been involved in the care of dermatology patients for the last nine years and completing the English National Board course 393 at St John's, I am interested in hearing from other Royal College of Nursing dermatology nurses who will be prepared to pioneer a special interest group in this field. PMID- 27413971 TI - Counselling service. AB - I was delighted that the agenda Item 3 at the Royal College of Nursing Congress, which requested Council to urge all health authorities to provide counselling services for all nurses, was carried so enthusiastically. PMID- 27413972 TI - ? AB - "I don't care what you used to do in the wild-life park, that's not how we tranquilise patients here." PMID- 27413973 TI - Challenging words. AB - I am writing to challenge certain statements made in Charlotte Aldermans' article 'Unproductive Labour' (Nursing Standard May 21 1988). To quote 'It is now clear that the combined pill is a cause of venous thrombosis and embolism, thrombotic stroke and myocardial infarction.' I would suggest that this situation is still far from 'clear', that the statement has been taken out of context, and as such is alarmist in the extreme. As is: 'the association between pill taking and carcinoma of fhe cervix has been made but is not yet established' - the implication being that this is only a matter of time and as such may also cause considerable anxiety. PMID- 27413974 TI - Handmaiden image. AB - I am writing on behalf of the [illegible word] Area Group of Practice [illegible word] in reply to the article by Karen Moss, Chairman of the RCN District Nurses Forum, called 'White Paper a threat to district nurses' (Primary Health CareMay 1988). PMID- 27413975 TI - Dangers of the box. AB - If epidemiologists weren't so smart, television could be carrying a health warning by now. PMID- 27413976 TI - What's going on ear. AB - We've all heard of iatrogenic disease and it comes in many forms. But one of the oddest we've come across appeared in the foreign news section ofThe Guardian. PMID- 27413978 TI - Takeaway currie. AB - Food glorious food. While one government minister was tucking into a hearty breakfast as part of a health campaign in Northern Ireland (choice of fruit juices, fresh fruit, cereals with semi-skimmed milk, wholemeal bread and rolls with butter, polyunsaturated margarine or low-fat spreads. In case you're interested) patients at a hospital in South London were reported to be on hunger strike because they'd been offered eight eggs between 24 for breakfast. PMID- 27413977 TI - Praise the ward. AB - Some fulsome words of praise have been coming the way of practice nurses. Often much maligned, they'll be very pleased to know that someone has been singing their praises. PMID- 27413979 TI - Bleep me up scotty! AB - Life is full of bleeps these days. Apart from bleeping doctors and senior nurses, the ubiquitous aircall bleep seems to be as essential as the Filofax in certain quarters. Not to mention bleeping watches (which usually emit insistent bip-bip bips during the quiet bits when you're at the cinema). PMID- 27413981 TI - Canada. AB - Free condoms, syringes and needles should be distributed by the government to intravenous drug abusers throughout the country, according to a study by the Royal Society of Canada into the spread of AIDS. PMID- 27413980 TI - Monkey business. AB - Whoever thought that AIDS would save a life? We're afraid it falls to this week's 'sad but true' slot to tell the tale. PMID- 27413982 TI - Third world. AB - Around 70,000 children in the developing world the of diarrhoeal infections every day, says a report sponsored by the Association of the British Pharmaceutical Industry. PMID- 27413984 TI - Portugal. AB - Serious concern-and condemnation from all quarters-has been expressed over the government's plans to close the Julio de Matos-the largest psychiatric hospital in Portugal. PMID- 27413983 TI - South africa. AB - The Red Cross is teaching life-saving skills to tuberculosis sufferers in South Africa, where 20 black people the each day from the disease. PMID- 27413986 TI - Listings. AB - Nursing Standard's listings section is a completely free service for its readers. To ensure maximum publicity for any event connected with your profession, be sure to let us know so that it can be included in our exhaustive nationwide guide to what's on in nursing. PMID- 27413985 TI - Triple time. AB - Three's a crowd, goes the old adage. Sometimes there is not much choice about the matter. Kay McCafferty, a 37 year old midwife in Doncaster, is now home on doctor's orders. Marrying in her mid thirties, within the space of 16 months she was mother of four. PMID- 27413987 TI - Hot air prevents bunsen burning. AB - Latex may protect laboratory workers' hands from infection butit is highly inflammable and hazardous around bunsen burner flames. Now Carbolite Furnaces and Sheffield University have produced a device to prevent accidents. PMID- 27413988 TI - Keep taking the tablets. AB - The immunosuppressive agent Sandimmun is now available in a soft gelatin capsule as well as the original oral solution. PMID- 27413989 TI - Infusion pumps provide smooth delivery. AB - Two new infusion pumps from[illegible word]and Nephew-Avon Pharmaceuticals are now available. PMID- 27413990 TI - Seaweed dressing speeds healing. AB - Community nurses will soon have access to a calcium alginatedressing that hospital nurses have been using for five years. PMID- 27413991 TI - Improved communications. AB - Tunstall Telecom has updated its alarm system for people who live alone with the launch of Lifeline II. PMID- 27413992 TI - Space age scrubbing with ultrasonics. AB - Intricate equipment can now be cleaned thoroughly using a rangeof self-contained ultrasonic cleaning units from Apollo Electronics. PMID- 27413993 TI - Hyper active. PMID- 27413994 TI - Borderline and cluster C personality disorders manifest distinct physiological responses to psychosocial stress. AB - BACKGROUND: Maladaptive emotional control is a defining feature of personality disorders. Yet little is known about the underlying physiological dynamics of emotional reactivity to psychosocial stress across distinct personality disorders. The current study compared subjective emotional responses with autonomic nervous system and HPA axis physiological responses to psychosocial stress in women with cluster C personality disorder (CPD) and borderline personality disorder (BPD). METHODS: Subjective mood ratings, salivary cortisol, heart rate (HR), and skin conductance level (SCL) were assessed before, during, and after exposure to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) in 26 women with BPD, 20 women with CPD, and 35 healthy female controls. Subjects were free of any medication including hormonal contraceptives, had a regular menstrual cycle, and were tested during the luteal phase of their menstrual cycle. RESULTS: Both CPD and BPD patients reported a similar burden of subjective mood disturbance. However, only BPD patients demonstrated reduced baseline cortisol levels with a blunted cortisol and HR reactivity to the TSST. In addition, BPD patients exhibited a generalized increase of SCL. No significant differences in baseline or TSST reactivity of cortisol, HR, or SCL were observed between CPD patients and healthy controls. CONCLUSION: These findings indicate that patients with BPD have significant alterations in their physiological stress reactivity, which is notably distinct from patients with CPD and those of healthy controls. PMID- 27413995 TI - Isolated splenic metastasis from a thymic carcinoma: A case report. AB - Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases. PMID- 27413996 TI - MODIFICATION OF ADJUSTABLE MACULAR BUCKLING WITH 29-G CHANDELIER LIGHT FOR OPTIMAL POSITIONING IN HIGHLY MYOPIC EYES WITH MACULAR HOLE. AB - PURPOSE: To evaluate the efficacy of the modification of Adjustable Macular Buckling device in the treatment of myopic macular hole retinal detachment with posterior staphyloma. METHODS: Four consecutive patients suffering from myopic macular detachment with macular hole were treated using the macular buckling procedure. An Adjustable Macular Buckling device was used in all four cases and was modified using a 29-gauge optical fiber to illuminate its macular plate. RESULTS: Optical coherence tomography showed successful retinal reattachment and closure of the macular hole after the buckling procedure. The macular plate of the buckling device was properly positioned in all four patients. No complications were observed. CONCLUSION: The modification of the macular buckling device improves the accuracy of its positioning by illuminating its macular plate. PMID- 27413997 TI - Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015. AB - Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Delta(9) tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention. PMID- 27413998 TI - Effects of thymol and carvacrol on T-helper cell subset cytokines and their main transcription factors in ovalbumin-immunized mice. AB - Thymol and carvacrol, two main components of thyme, have several valuable effects on the immune system. This study aims to evaluate the effects of these components on T-helper (TH) cell responses and their subsets in mice immunized with ovalbumin. The effects of these components on: a specific in vivo immune response were evaluated by assessing changes in delayed-type hypersensitivity (DTH); ex vivo splenocyte proliferative responses were evaluated using a BrdU assay gene expression of cytokines and key transcription factors involved in T-cells subset differentiation among the mouse splenocytes were assessed using real-time polymerase chain reaction (PCR); and splenocyte cytokine formation (ex vivo) and levels of the cytokines in mouse sera were measured by ELISA. Mice treated with thymol or carvacrol had reduced DTH responses (26% and 50%, respectively) compared with control mice. Thymol and carvacrol each diminished splenocyte proliferation to nearly 65-72% of control levels (p < 0.01). These agents also led to decreased TH1 [interleukin (IL)-2, interferon (IFN)-gamma)], TH2 (IL-4) and TH17 (IL-17A) levels in the splenocyte cultures and in the sera of mice but increased levels of IL-10 and transforming growth factor (TGF)-beta. Treated immunized mice showed significantly reduced T-box 21 (T-bet) expression from 3.8 [+/- 0.3]-fold in untreated ovalbumin-immunized mice to 0.9 [+/- 0.4]-(thymol) and 0.8 [+/- 0.2]-fold (carvacrol) (p < 0.01). GATA binding protein 3 (GATA-3) expression declined from 3.4 [+/- 0.4]- to 0.5 [+/- 0.3]-fold (thymol) and 0.6 [+/- 0.4]-fold (carvacrol), whereas RORgammac decreased from 13.4 [+/- 1.6]- to 1.5 [+/- 0.6]-fold (thymol) and 0.8 [+/- 0.4]-fold (carvacrol) (p < 0.001). As carvacrol and thymol each suppressed the antigen-specific immune response by reducing TH cell-related cytokines?specific transcription factors, this indicated their potential to modulate destructive immune responses attributed to T-cells over-activation. PMID- 27414000 TI - Consumers' Understanding of FDA Approval Requirements and Composite Scores in Direct-to-Consumer Prescription Drug Print Ads. AB - In 2 studies, we investigated how laypersons perceive the Food and Drug Administration (FDA) approval process, FDA authority, and the presentation of composite scores in direct-to-consumer (DTC) prescription drug print ads. The 1st study consisted of 4 focus groups (N = 38) in 2 cities. Using a semi-structured guide, a moderator led participants through the viewing of 3 existing DTC print ads that differed in the presence or absence of composite score information, and participants discussed their views of the ads and their understanding of composite scores. The 2nd study surveyed a nationally representative sample of 1,629 individuals from the general population who saw a fictitious DTC print ad and answered closed-ended questions about the same topics. Results showed that knowledge of FDA approval and authority was mixed, with several misconceptions apparent. Many consumers were not familiar with the use of composite scores in a medical context or in advertising and, in the 1st study, expressed distrust of the product and the ad after learning about how composite scores are used. In the 2nd study, receiving composite score information changed the perceived clarity of the ad but not the perceived risk or benefits. Implications for the presentation of complex medical information are discussed. PMID- 27414001 TI - The time and cost investment required to obtain and initiate direct-acting antiviral therapy. AB - BACKGROUND: Obtaining direct-acting antiviral (DAA) medications for treatment of HCV is labour-intensive for providers. The purpose of this study was to assess the amount of unbillable time and to estimate the financial burden of obtaining DAAs for HCV. METHODS: Patients prescribed DAA therapy from 30 September 2014 to 19 March 2015 at an academic hepatology practice were enrolled prospectively. Providers recorded the amount of time required to obtain HCV therapy for each patient. RESULTS: A total of 79 patients consented, 27 of whom were excluded due to incomplete data or deferment of therapy. In our patient population 56% of patients had private insurance, 27% Medicare and 15% Medicaid. The median time spent per patient was 92.5 min (IQR 80.00-108.80). The median cost spent per patient was $78.85 (IQR 66.75-94.30). CONCLUSIONS: Development of a streamlined process to reduce the time and cost for physicians to obtain DAAs is needed. Removing this barrier will encourage physicians to adopt HCV treatment to address the large number of patients in need. PMID- 27413999 TI - Physico-Chemical Strategies to Enhance Stability and Drug Retention of Polymeric Micelles for Tumor-Targeted Drug Delivery. AB - Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on PM have resulted in tremendous numbers of PM-forming amphiphilic polymers, and approximately a dozen micellar nanomedicines have entered the clinic. The first generation of PM can be considered solubilizers of hydrophobic drugs, with short circulation times resulting from poor micelle stability and unstable drug entrapment. To more optimally exploit the potential of PM for targeted drug delivery, several physical (e.g., pi-pi stacking, stereocomplexation, hydrogen bonding, host-guest complexation, and coordination interaction) and chemical (e.g., free radical polymerization, click chemistry, disulfide and hydrazone bonding) strategies have been developed to improve micelle stability and drug retention. In this review, the most promising physico-chemical approaches to enhance micelle stability and drug retention are described, and how these strategies have resulted in systems with promising therapeutic efficacy in animal models, paving the way for clinical translation, is summarized. PMID- 27414002 TI - Introduction to the Special Issue for World Association for Plastic Surgeons of Chinese Descent. PMID- 27414003 TI - The Fourth World Congress for Plastic Surgeons of Chinese Descent. PMID- 27414004 TI - Expanded Cheek-Shaped Flap for Aesthetic Cheek Reconstruction in the Cervicoperiauricular Area. AB - BACKGROUND: The cervical area is well acknowledged as an ideal donor site for aesthetic reconstruction of the cheek, and tissue expansion may play an important role for maximally achieving such a purpose. However, the conventional design of the expanded cervical flap generally results in unsightly morbidity of the donor site. The aim of this study is to evaluate the results of using an improvised cervical expanded flap in aesthetic reconstruction of the cheek. METHODS: From July 2004 to October 2012, a total of 23 burn sequelae patients (30 cheeks) underwent cheek reconstruction with an expanded flap that originated from the cervicoperiauricular area. The procedures were initially carried out with the insertion of a round tissue expander in the cervicoperiauricular area, followed by serial inflation of the expander, and finally, transplantation of the expanded flap to the cheek in a rotation advancement fashion. The donor site closure was along the auricular sulcus. RESULTS: The average area of the harvested flaps was 9.7 * 8.1 cm. All the flaps completely survived, only one major complication occur-a dome exposure of the tissue expander after the expansion was completed. The flap was salvaged, and the transfer stage was done without intact. Minor complications after flap transfer include: widened scar at the donor site, a "dog ear" needing additional minor surgery, distal part of the flap transient congestion. The patients achieved very satisfactory results functionally and aesthetically. CONCLUSIONS: Using the expanded cheek-shaped flap technique can provide a safe, thin, and color-matched flap in aesthetic reconstruction of the cheek with minimal donor site morbidity. PMID- 27414005 TI - Post-Bariatric Body Contouring Surgery After Weight Loss: Lessons Learned From an Obesity Epidemic in the United States. AB - With the rise in obesity in the United States, there has been a similar increase in bariatric surgery. This has resulted in numerous patients losing significant weight with accompanying circumferential body contouring issues. This has led to an amazing increase in the number of body contouring procedures performed, both traditional excisional techniques as well as new emerging techniques emphasizing tissue preservation, rearrangement, and dermal reshaping. Although China's rates of obesity lag behind the United States, there is a recipe for obesity that will eventually surpass the United States. Thus, China has the opportunity to learn from the United States experience with regards to obesity treatment and contouring procedures after significant weight loss. Time will tell whether China will choose to use similar tissue preservation techniques to address issues of soft tissue ptosis and volume deficiency seen after significant weight loss, make refinements of these techniques, or develop new uniquely Chinese solutions. PMID- 27414006 TI - Associations of Domain-Specific Physical Activity With Leisure-Time Sedentary Behaviors in Chinese Professionals. AB - OBJECTIVE: To understand the association of domain-specific physical activity (PA) with leisure-time sedentary behavior (LTSB) among Chinese professionals. METHODS: Totally, 3326 workers aged 35 to 64 years old from Beijing city and Zhejiang province were asked information on domain-specific PA with a revised Global Physical Activity Questionnaire (GPAQ). The association of domain-specific PA with LTSB-lifestyle (>=4 hours/day spent on LTSB) was examined with a binary logistic regression model. RESULTS: Compared with sedentary occupational activity (OA), light-, moderate-, and vigorous-intensity OA were respectively associated with 55.3% (ORs, 0.447; 95%CI, 0.378 to 0.529), 63.5% (ORs, 0.365; 95%CI, 0.285 to 0.468), and 77.1% (ORs, 0.229; 95%CI, 0.126 to 0.417) less the odds of having LTSB-lifestyle. Those performing domestic activity (DA) are greater than and equal to 19.6 MET-hours/week had 30.1% (ORs, 0.699; 95%CI, 0.576 to 0.848) less the odds. CONCLUSIONS: Both non-sedentary occupations and DA were negatively associated with LTSB-lifestyle in these professionals. PMID- 27414008 TI - Building Resilience in an Urban Police Department. AB - OBJECTIVE: The aim of this study is to examine a resilience training intervention that impacts autonomic responses to stress and improves cardiovascular risk, psychological, and physiological outcomes in police. METHODS: Officers [(n = 38) 22 to 54 years] modified emotional and physical responses to stress using self regulation. Measurements include psychological and physiological measures [eg, heart rate variability (HRV), blood pressure, C-reactive protein)] obtained at three time intervals. RESULTS: Age was significantly (P < 0.05) associated with changes on several measures of psychological stress (eg, critical incident stress, emotional vitality, and depression). Associations were found between coherence and improved HbA1c (r = -0.66, P < 0.001) and stress due to organizational pressures (r = -0.44, P = 0.03). Improvements in sympathetic and parasympathetic contributors of HRV were significant (P < 0.03). CONCLUSION: A stress-resilience intervention improves certain responses to job stress with greater benefits for younger participants. PMID- 27414007 TI - Impact of Work Organizational Factors on Carpal Tunnel Syndrome and Epicondylitis. AB - OBJECTIVE: The aim of this study was to identify relationships between work organizational variables (job rotation, overtime work, having a second job, and work pacing) (These work organizational variables and their relationships with biomechanical and psychosocial exposures were studied previously and published in a separate paper.) and health outcome measures [carpal tunnel syndrome (CTS), lateral and medial epicondylitis (LEPI/MEPI)]. METHODS: Using a pooled baseline cohort of 1834 subjects, the relationships were studied using logistic regression models. RESULTS: Varied degrees of associations between the work organizational and outcomes variables were found. Job rotation was significantly associated with being a CTS case [odds ratio (OR) = 1.23, 95% confidence interval (95% CI): 1.00 to 1.50]. Overtime work was significantly associated with lower LEPI prevalence (OR = 0.48, 95% CI: 0.28 to 0.84). No statistically significant associations were found between having a second job and different work pacing and any of the three health outcome measures. CONCLUSIONS: Work organizational variables were only partially associated with the studied health outcomes. PMID- 27414009 TI - Research to Practice Implications of High-Risk Genotypes for Beryllium Sensitization and Disease. AB - OBJECTIVE: Beryllium workers may better understand their genetic susceptibility to chronic beryllium disease (CBD) expressed as population-based prevalence, rather than odds ratios from case-control studies. METHODS: We calculated CBD prevalences from allele-specific DNA sequences of 853 workers for Human Leukocyte Antigen (HLA)-DPB1 genotypes and groups characterized by number of E69-containing alleles and by calculated surface electronegativity of HLA-DPB1. RESULTS: Of 18 groups of at least 10 workers with specific genotypes, CBD prevalence was highest, 72.7%, for the HLA-DPB102:01:02/DPB117:01 genotype. Population-based grouped genotypes with two E69 alleles wherein one allele had -9 surface charge had a beryllium sensitization (BeS) of 52.6% and a CBD prevalence of 42.1%. CONCLUSIONS: The high CBD and BeS prevalences associated with -9-charged E69 alleles and two E69s suggest that workers may benefit from knowing their genetic susceptibility in deciding whether to avoid future beryllium exposure. PMID- 27414010 TI - The Association Between Cardiovascular Disease Risk Factors and Motor Vehicle Crashes Among Professional Truck Drivers. AB - OBJECTIVE: This study assesses relationships between the Framingham cardiovascular disease risk (CVD risk) score and prevalence of US Department of Transportation (DOT)-reportable crashes in commercial motor vehicle (CMV) drivers, after controlling for potential confounders. METHODS: Data were analyzed from CMV drivers (N = 797) in a large cross-sectional study. CVD risk was calculated for each driver. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) between CVD risk and DOT-reportable crashes were calculated. RESULTS: Drivers in the two highest CVD risk groups had significantly higher likelihood of crash (OR = 2.08, 95% CI = 1.20 to 3.63 and OR = 1.99, 95% CI = 1.05 to 3.77, respectively) after adjusting for confounders. There was a significant trend of increasing prevalence of crashes with an increasing CVD risk score (P = 0.0298). CONCLUSION: Drivers with a high CVD risk had a higher likelihood of a crash after controlling for confounders. PMID- 27414011 TI - A Case-Control Study of Maternal Occupation and the Risk of Orofacial Clefts. AB - OBJECTIVES: The aim of this study was to examine the association between maternal occupation and risk of orofacial clefts in offspring. METHODS: Data were obtained from the Texas Birth Defects Registry and vital records for 1999 to 2009 deliveries. We used automated software to assist in classifying occupations into standard codes. Using multivariable logistic regression, the risk for cleft lip with or without cleft palate (CLP) or cleft palate only (CP) in offspring was compared between women in each of 20 major occupation groups to women in every other occupation group. RESULTS: Significant positive associations were observed between business/finance and architecture/engineering occupations and CP and between cleaning-related occupations and CLP. A significant negative association was observed between office and administrative support occupations and CLP. CONCLUSIONS: This study supports previous reports of increased risk of orofacial clefts in offspring among women in certain occupations. PMID- 27414012 TI - Association of Sleep Quality With Cardiovascular Disease Risk and Mental Health in Law Enforcement Officers. AB - OBJECTIVES: The aim of the study was to determine whether sleep quality is associated with an increased risk for cardiovascular disease (CVD) or worsened mental health. METHODS: Self-reported sleep quality, 35 inflammatory factors, CVD risk factors, personal stress, police operational and organizational stress, social support, depressive symptoms, and health-related quality of life were compared among a cohort of officers. RESULTS: Of 379 officers, 39% and 27% had poor and borderline sleep quality. Sleep quality was not associated with either an altered inflammatory profile or worsened CVD risk factors. Compared with good sleepers, borderline and poor sleepers reported increased personal stress, police organizational and operational stress, and depressive symptoms, but decreased health-related quality of life. CONCLUSIONS: Poor sleep quality is prevalent in the law enforcement profession and is associated with worsened mental health but not with an increased risk for CVD. PMID- 27414013 TI - What Should Be the Content and Frequency of Performing a Medical Evaluation to Determine Fitness to Wear a Respirator? AB - OBJECTIVE: The aim of this study was to assess the standard of care among occupational medicine practioners for determining medical fitness to wear a respirator. METHODS: A 15-item email/telephone survey was conducted of members of the Michigan Occupational and Environmental Medical Association. RESULTS: Sixty seven percent of occupational medicine practioners who responded performed respirator evaluations; 75% did more than just the required Occupational Safety Health Administration questionnaire. Cardiovascular and respiratory symptoms and problems wearing a respirator (87% to 95%) were the most common reasons for additional testing and denying medical clearance (58% to 82%). Sixty percent of practioners required workers to have an annual evaluation. CONCLUSIONS: The frequency of medical evaluation, which specific tests were performed, and the criteria used to determine fitness to wear a respirator varied markedly between practioners. Further research is needed to determine whether the widespread variation is a sign of too little or too much testing by different practioners. PMID- 27414014 TI - The Association Between Health Program Participation and Employee Retention. AB - OBJECTIVE: Using health plan membership as a proxy for employee retention, the objective of this study was to examine whether use of health promotion programs was associated with employee retention. METHODS: Propensity score weighted generalized linear regression models were used to estimate the association between telephonic programs or health risk surveys and retention. Analyses were conducted with six study samples based on type of program participation. RESULTS: Retention rates were highest for employees with either telephonic program activity or health risk surveys and lowest for employees who did not participate in any interventions. Participants ranged from 71% more likely to 5% less likely to remain with their employers compared with nonparticipants, depending on the sample used in analyses. CONCLUSIONS: Using health promotion programs in combination with health risk surveys may lead to improvements in employee retention. PMID- 27414015 TI - The Effects of Occupational Exposure of Carbon Disulfide on Sexual Hormones and Semen Quality of Male Workers From a Chemical Fiber Factory. AB - OBJECTIVE: This study is aimed to analyze the relationship between occupational CS2 exposure and reproductive impairments. METHODS: Seventy-six CS2-exposed (9.73 +/- 2.76 mg/m(3)) male workers and 94 unexposed workers were selected for study. Worker demographics were assessed with a customized questionnaire. Sexual hormones and sperm-related parameters were measured by biochemical or morphological analysis. RESULTS: The CS2-exposed workers had significantly higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and lower levels of testosterone (T). Significant decrements were also identified in sperm viability and motility, chromatin, antioxidant capacity, mitochondrial membrane potential, mitochondrial membrane permeability transition pore (MPTP), and respiratory chain Complexes II and IV. CONCLUSIONS: Our data indicated that occupational CS2 exposure can exert deleterious effects on male sexual hormones and sperm quality, and mitochondrial dysfunction may play a vital role in this process. PMID- 27414017 TI - Electron Correlation Effects in All-Metal Aromatic Clusters: A Quantum Monte Carlo Study. PMID- 27414016 TI - The Impact of Worksite Supports for Healthy Eating on Dietary Behaviors. AB - OBJECTIVE: The purpose of this study was to assess the availability of worksite supports (WSS) for healthy eating and examine associations between existing supports and dietary behaviors. METHODS: A cross-sectional, telephone-based study was conducted with 2013 participants in four metropolitan areas in 2012. Logistic regression was used to examine associations between dietary behaviors and the availability or use of WSS. RESULTS: Those reporting the availability of a cafeteria/snack bar/food services at the worksite were more likely to consume fruits and vegetables more than twice/day, and less likely to consume fast food more than twice/week. CONCLUSIONS: Study results highlight the utility of specific WSS to improve employee dietary behaviors while raising questions about why the presence of healthy foods at the worksite may not translate into employee consumption of such foods. PMID- 27414018 TI - Reefs of tomorrow: eutrophication reduces coral biodiversity in an urbanized seascape. AB - Although the impacts of nutrient pollution on coral reefs are well known, surprisingly, no statistical relationships have ever been established between water quality parameters, coral biodiversity and coral cover. Hong Kong provides a unique opportunity to assess this relationship. Here, coastal waters have been monitored monthly since 1986, at 76 stations, providing a highly spatially resolved water quality dataset including 68 903 data points. Moreover, a robust coral species richness (S) dataset is available from more than 100 surveyed locations, composed of 3453 individual colonies' observations, as well as a coral cover (CC) dataset including 85 sites. This wealth of data provides a unique opportunity to test the hypothesis that water quality, and in particular nutrients, drives coral biodiversity. The influence of water quality on S and CC was analyzed using GIS and multiple regression modeling. Eutrophication (as chlorophyll-a concentration; CHLA) was negatively correlated with S and CC, whereas physicochemical parameters (DO and salinity) had no significant effect. The modeling further illustrated that particulate suspended matter, dissolved inorganic nitrogen (DIN) and dissolved inorganic phosphorus (DIP) had a negative effect on S and on CC; however, the effect of nutrients was 1.5-fold to twofold greater. The highest S and CC occurred where CHLA <2 MUg L-1 , DIN < 2 MUm and DIP < 0.1 MUm. Where these values were exceeded, S and CC were significantly lower and no live corals were observed where CHLA > 15 MUg L-1 , DIN > 9 MUm and DIP > 0.33 MUm. This study demonstrates the importance of nutrients over other water quality parameters in coral biodiversity loss and highlights the key role of eutrophication in shaping coastal coral reef ecosystems. This work also provides ecological thresholds that may be useful for water quality guidelines and nutrient mitigation policies. PMID- 27414019 TI - Revealing the radiative and non-radiative relaxation rates of the fluorescent dye Atto488 in a lambda/2 Fabry-Perot-resonator by spectral and time resolved measurements. AB - Using a Fabry-Perot-microresonator with controllable cavity lengths in the lambda/2-regime, we show the controlled modification of the vibronic relaxation dynamics of a fluorescent dye molecule in the spectral and time domain. By altering the photonic mode density around the fluorophores we are able to shape the fluorescence spectrum and enhance specifically the probability of the radiative transitions from the electronic excited state to distinct vibronic excited states of the electronic ground state. Analysis and correlation of the spectral and time resolved measurements by a theoretical model and a global fitting procedure allows us to reveal quantitatively the spectrally distributed radiative and non-radiative relaxation dynamics of the respective dye molecule under ambient conditions at the ensemble level. PMID- 27414021 TI - Bioresorbable vascular scaffold use for coronary bifurcation lesions: A substudy from GHOST EU registry. AB - OBJECTIVES: The aim of this study was to evaluate midterm outcomes of bioresorbable vascular scaffolds (BVS) implanted in bifurcation lesions. BACKGROUND: BVS have emerged as an alternative to conventional metallic drug eluting stents for the treatment of coronary complex lesions. METHODS: Between November 2011 and January 2014, 1189 patients underwent percutaneous coronary intervention with BVS at 10 European centers (GHOST EU registry). Of these, 289 consecutive patients (302 bifurcation lesions) treated with either single stenting (n = 260) or double-stenting (n = 42) were evaluated. RESULTS: True bifurcations were treated in 44.7%. Intravascular ultrasound and optical coherence tomography were utilized only in 22.2% and 21.2%, respectively. Predilation was performed in 95.4%, while postdilation of the main branch was performed in 61.3%. Final kissing inflation with no or minimal protrusion of a side-branch balloon into main branch was performed in 18.9%. Median follow-up period was 356 (IQR 191-419) days. The Kaplan-Meier estimated rates of target lesion failure and scaffold thrombosis (ST) were 6.4% and 2.5% at 360 days, respectively. Independent predictors for TLF were ACS and diabetes mellitus (HR 4.67; 95% CI: 1.78-12.3; P = 0.002 and HR 3.37; 95% CI: 1.38-8.26; P = 0.008, respectively). CONCLUSIONS: BVS use for coronary bifurcation lesions in an "all comer" population was associated with acceptable TLF rates up to midterm follow up. However, ST rates were higher than seen with contemporary metallic stents possibly due to the low incidence of intravascular guidance and postdilation resulting in a higher likelihood of scaffold underexpansion and malapposition, further supporting the importance of meticulous implantation technique. (c) 2016 Wiley Periodicals, Inc. PMID- 27414022 TI - Alternative Start Codon Connects eIF5A to Mitochondria. AB - Eukaryotic translation initiation factor 5A (eIF5A), a protein containing the amino acid residue hypusine required for its activity, is involved in a number of physiological and pathological cellular processes. In humans, several EIF5A1 transcript variants encode the canonical eIF5A1 isoform B, whereas the hitherto uncharacterized variant A is expected to code for a hypothetical eIF5A1 isoform, referred to as isoform A, which has an additional N-terminal extension. Herein, we validate the existence of eIF5A1 isoform A and its production from transcript variant A. In fact, variant A was shown to encode both eIF5A1 isoforms A and B. Mutagenic assays revealed different efficiencies in the start codons present in variant A, contributing to the production of isoform B at higher levels than isoform A. Immunoblotting and mass spectrometric analyses showed that isoform A can undergo hypusination and acetylation at specific lysine residues, as observed for isoform B. Examination of the N-terminal extension suggested that it might confer mitochondrial targeting. Correspondingly, we found that isoform A, but not isoform B, co-purified with mitochondria when the proteins were overproduced. These findings suggest that eIF5A1 isoform A has a role in mitochondrial function. J. Cell. Physiol. 231: 2682-2689, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27414023 TI - The Fatty Kidney: Obesity and Renal Disease. AB - Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly accompanied in many patients by lesions of focal and segmental glomerulosclerosis. Slowly increasing subnephrotic proteinuria is the commonest presentation of ORG. Occasionally, massive proteinuria (>5-10 g/day) is detected, but the typical findings of nephrotic syndrome are characteristically absent even in patients with massive proteinuria. Superimposed obesity can fuel the progression of other renal diseases, and a reduced number of functioning nephrons (of congenital or acquired causes) synergizes with obesity to induce end-stage renal disease. Weight loss, either induced by diet or bariatric surgery, and renin-angiotensin blockers are effective treatments to slow progression, but a significant proportion of cases will develop end-stage renal disease. PMID- 27414024 TI - Association between Sickle Cell Trait and the Prevalence and Severity of Diabetic Retinopathy. AB - PURPOSE: To determine whether Sickle cell trait (SCT) is associated with an increased severity of diabetic retinopathy. METHODS: This was a single center retrospective study case control study of 100 eyes of 100 patients with diabetes mellitus (DM) with SCT (SCT group) and 100 eyes of 100 age-matched patients with DM without SCT (control group). The main outcome measure was the difference in the prevalence of sight threatening DR [here defined as diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR)], between the SCT and control groups. Secondary outcome measures included differences in visual acuity, ocular comorbidities, intraocular pressure, glycemic control as assessed by random blood glucose measurement, diabetes duration, nephropathy, hyperlipidemia and hypertension. RESULTS: The SCT group had statistically significantly shorter duration of DM (median [25% quartile] 15 [8.3] years versus 20 [14.7] years, respectively)(P<0.001) and presented with statistically better metabolic control (mean difference 1.6 mmol/l, (95% confidence interval [CI], 0.1-3.3;P = 0.03). The prevalence of PDR and/or DME was significantly lower in the SCT group (58%) compared to the control group, (95%)(P<0.001). The absence of SCT (adjusted odds ratio [AOR] = 24; 95% CI, 8-72; P<0.001) and longer duration of DM (AOR = 1.1 [95% CI, 1.02-1.13]; P = 0.003) were independent predictors of PDR and/or DME. CONCLUSIONS: SCT seems to protect against the development and progression of DR. This may have implications for monitoring and screening. Prospective studies are required to confirm this association. If true, this association may indicate an increased blood glucose buffering capacity of abnormal hemoglobin. PMID- 27414025 TI - Dynamics of Chloroplast Translation during Chloroplast Differentiation in Maize. AB - Chloroplast genomes in land plants contain approximately 100 genes, the majority of which reside in polycistronic transcription units derived from cyanobacterial operons. The expression of chloroplast genes is integrated into developmental programs underlying the differentiation of photosynthetic cells from non photosynthetic progenitors. In C4 plants, the partitioning of photosynthesis between two cell types, bundle sheath and mesophyll, adds an additional layer of complexity. We used ribosome profiling and RNA-seq to generate a comprehensive description of chloroplast gene expression at four stages of chloroplast differentiation, as displayed along the maize seedling leaf blade. The rate of protein output of most genes increases early in development and declines once the photosynthetic apparatus is mature. The developmental dynamics of protein output fall into several patterns. Programmed changes in mRNA abundance make a strong contribution to the developmental shifts in protein output, but output is further adjusted by changes in translational efficiency. RNAs with prioritized translation early in development are largely involved in chloroplast gene expression, whereas those with prioritized translation in photosynthetic tissues are generally involved in photosynthesis. Differential gene expression in bundle sheath and mesophyll chloroplasts results primarily from differences in mRNA abundance, but differences in translational efficiency amplify mRNA-level effects in some instances. In most cases, rates of protein output approximate steady state protein stoichiometries, implying a limited role for proteolysis in eliminating unassembled or damaged proteins under non-stress conditions. Tuned protein output results from gene-specific trade-offs between translational efficiency and mRNA abundance, both of which span a large dynamic range. Analysis of ribosome footprints at sites of RNA editing showed that the chloroplast translation machinery does not generally discriminate between edited and unedited RNAs. However, editing of ACG to AUG at the rpl2 start codon is essential for translation initiation, demonstrating that ACG does not serve as a start codon in maize chloroplasts. PMID- 27414026 TI - A Longitudinal Analysis of General Practitioner Service Use by Patients with Mild Cognitive Disorders in Australia. AB - BACKGROUND: The aim of this study was to ascertain if participants diagnosed with any mild cognitive disorder (MCD) visited a general practitioner (GP) more than those without MCD and the effect of either depression or arthritis on GP use longitudinally. METHODS: 2,551 participants aged 60-64 years at baseline completed the Personality and Total Health Through Life (PATH) study in Canberra. Follow-up data were collected after 4 and 8 years. A cognitive screening battery was used to screen participants into a substudy of MCD. RESULTS: Participants with any MCD had greater GP use than cognitively healthy participants across all three waves (wave 1, M = 7.35 vs. 5.59; wave 2, M = 7.77 vs. 5.86; wave 3, M = 9.01 vs. 6.81). After adjusting for demographic and health factors, MCD was a significant predictor of GP use at all three waves (p < 0.05, CI 0.84-0.99). CONCLUSION: This study has shown that MCD is associated with a higher use of GP visits, especially if the patient has a comorbid condition. PMID- 27414027 TI - Comorbid Analysis of Genes Associated with Autism Spectrum Disorders Reveals Differential Evolutionary Constraints. AB - The burden of comorbidity in Autism Spectrum Disorder (ASD) is substantial. The symptoms of autism overlap with many other human conditions, reflecting common molecular pathologies suggesting that cross-disorder analysis will help prioritize autism gene candidates. Genes in the intersection between autism and related conditions may represent nonspecific indicators of dysregulation while genes unique to autism may play a more causal role. Thorough literature review allowed us to extract 125 ICD-9 codes comorbid to ASD that we mapped to 30 specific human disorders. In the present work, we performed an automated extraction of genes associated with ASD and its comorbid disorders, and found 1031 genes involved in ASD, among which 262 are involved in ASD only, with the remaining 779 involved in ASD and at least one comorbid disorder. A pathway analysis revealed 13 pathways not involved in any other comorbid disorders and therefore unique to ASD, all associated with basal cellular functions. These pathways differ from the pathways associated with both ASD and its comorbid conditions, with the latter being more specific to neural function. To determine whether the sequence of these genes have been subjected to differential evolutionary constraints, we studied long term constraints by looking into Genomic Evolutionary Rate Profiling, and showed that genes involved in several comorbid disorders seem to have undergone more purifying selection than the genes involved in ASD only. This result was corroborated by a higher dN/dS ratio for genes unique to ASD as compare to those that are shared between ASD and its comorbid disorders. Short-term evolutionary constraints showed the same trend as the pN/pS ratio indicates that genes unique to ASD were under significantly less evolutionary constraint than the genes associated with all other disorders. PMID- 27414028 TI - An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression. AB - Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from a phagosome, rapid cytosolic growth, and ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA. The environmental cues that lead to temporal and spatial control of L. monocytogenes virulence gene expression are poorly understood. In this study, we took advantage of the robust up-regulation of ActA that occurs intracellularly and expressed Cre recombinase from the actA promoter and 5' untranslated region in a strain in which loxP sites flanked essential genes, so that activation of actA led to bacterial death. Upon screening for transposon mutants that survived intracellularly, six genes were identified as necessary for ActA expression. Strikingly, most of the genes, including gshF, spxA1, yjbH, and ohrA, are predicted to play important roles in bacterial redox regulation. The mutants identified in the genetic selection fell into three broad categories: (1) those that failed to reach the cytosolic compartment; (2) mutants that entered the cytosol, but failed to activate the master virulence regulator PrfA; and (3) mutants that entered the cytosol and activated transcription of actA, but failed to synthesize it. The identification of mutants defective in vacuolar escape suggests that up-regulation of ActA occurs in the host cytosol and not the vacuole. Moreover, these results provide evidence for two non-redundant cytosolic cues; the first results in allosteric activation of PrfA via increased glutathione levels and transcriptional activation of actA while the second results in translational activation of actA and requires yjbH. Although the precise host cues have not yet been identified, we suggest that intracellular redox stress occurs as a consequence of both host and pathogen remodeling their metabolism upon infection. PMID- 27414029 TI - Estrogen and Androgen Hormone Levels Modulate the Expression of PIWI Interacting RNA in Prostate and Breast Cancer. AB - PIWI interacting RNAs (piRNAs), a member of non-coding RNA, originate from intergenic repetitive regions of the genome. piRNA expressions increase in various cancers and it is thought that this increase could be caused by hormones. We aimed to determine the effects of hormones on piRNA expression in breast and prostate cancer. High viability and a decrease in adhesion were observed at the concentrations of the highest proliferation. Furthermore, an increase in adhesion was also observed in MDA-MB-231 cells. After hormone treatment, while piR-651 expression had increased both breast and prostate cancer cell lines, piR-823 expressions increased in prostate cancer cell lines and only in the breast cancer cell line which was malignant. Thus, it was determined that piR-823 might show different expressions in different type of cancers. PMID- 27414030 TI - The Effects of Low-Vision Rehabilitation on Reading Speed and Depression in Age Related Macular Degeneration: A Meta-Analysis. AB - IMPORTANCE: Age related macular degeneration (AMD) is a progressive eye disease that, as of 2015, has affected 11 million people in the U.S. and 1.5 million in Canada causing central vision blindness. By 2050, this number is expected to double to 22 million. Eccentric vision is the target of low-vision rehabilitation aids and programs for patients with AMD, which are thought to improve functional performance by improving reading speed and depression. OBJECTIVE: This study evaluates the effect of various low-vision rehabilitation strategies on reading speed and depression in patients 55 and older with AMD. DATA SOURCES: Computer databases including MEDLINE (OVID), EMBASE (OVID), BIOSIS Previews (Thomson Reuters), CINAHL (EBSCO), Health Economic Evaluations Database (HEED), ISI Web of Science (Thomson-Reuters) and the Cochrane Library (Wiley) were searched from the year 2000 to January 2015. STUDY SELECTION: Included papers were research studies with a sample size of 20 eyes or greater focused on AMD in adults aged 55 or older with low vision (20/60 or lower). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened and extracted relevant data from the included articles. Standardized mean difference (SMD) was chosen as an effect size to perform meta-analysis using STATA. Fixed- and random-effect models were developed based on heterogeneity. MAIN OUTCOMES: Reading Speed and Depression Scores. RESULTS: A total of 9 studies (885 subjects) were included. Overall, a significant improvement in reading speed was found with a SMD of 1.01 [95% CI: 0.05 to 1.97]. Low-vision rehabilitation strategies including micro-perimetric biofeedback, microscopes teaching program significantly improved reading speed. Eccentric viewing training showed the maximum improvement in reading speed. In addition, a non-significant improvement in depression scores was found with a SMD of -0.44 [95% CI: -0.96 to 0.09]. CONCLUSION: A considerable amount of research is required in the area of low-vision rehabilitation strategies for patients with AMD. Based on current research, low-vision rehabilitation aids improve reading speed. However, they do not have a significant effect on depression scores in those 55 and older with AMD. PMID- 27414031 TI - Seroepidemiological Evidence of Subtype H3N8 Influenza Virus Infection among Pet Dogs in China. AB - The H3N8 virus and the H3N2 virus are the main subtypes of canine influenza virus (CIV). H3N8 CIV mainly circulates in America, and H3N2 CIV mainly circulates in Asia. However, there was an outbreak of the Asian H3N2 virus in the United States (US) in 2015. Thus, it is important to evaluate the presence of subtype H3N8 virus in dogs in China. From May 2015 to November 2015, 600 sera from pet dogs were collected from Guangzhou, Shanghai, Beijing and Shenzhen for hemagglutination inhibition (HI) assays and microneutralization (MN) assays. Fifty-two (8.66%) of the 600 sera were positive for the subtype H3N2 virus, which matched the previous reports. Five (0.83%) of 600 sera were positive for the subtype H3N8 virus (H3N8 EIV or H3N8 AIV or H3N8 CIV), which is the first report of subtype H3N8 virus infection among dogs in China and remind us to play more attention to this subtype virus. Therefore, further serological and virological surveillance of influenza virus infection among dogs in China is imperative. PMID- 27414032 TI - Density of Key-Species Determines Efficiency of Macroalgae Detritus Uptake by Intertidal Benthic Communities. AB - Accumulating evidence shows that increased biodiversity has a positive effect on ecosystem functioning, but the mechanisms that underpin this positive relationship are contentious. Complete extinctions of regional species pools are comparatively rare whereas compositional changes and reductions in abundance and biomass are common, although seldom the focus of biodiversity-ecosystem functioning studies. We use natural, small-scale patchiness in the density of two species of large bivalves with contrasting feeding modes (the suspension-feeding Austrovenus stutchburyi and deposit-feeding Macomona liliana) to examine their influence on the uptake of nitrogen from macroalgae detritus (i.e. measure of ecosystem function and food web efficiency) by other infauna in a 10-d laboratory isotope-tracer experiment. We predicted that densities of these key bivalve species and functional group diversity (calculated as Shannons H, a density independent measure of community composition) of the intact infaunal community will be critical factors explaining variance in macroalgal per capita uptake rates by the community members and hence determine total uptake by the community. Results show that only two species, M. liliana and a large orbiniid polychaete (Scoloplos cylindrifer) dominated macroalgal nitrogen taken up by the whole community due to their large biomass. However, their densities were mostly not important or negatively influenced per capita uptake by other species. Instead, the density of a head-down deposit-feeder (the capitellid Heteromastus filiformis), scavengers (mainly nemertines and nereids) and species and functional group diversity, best explained per capita uptake rates in community members. Our results demonstrate the importance of species identity, density and large body size for ecosystem functioning and highlight the complex interactions underlying loss of ecological functions with declining biodiversity and compositional changes. PMID- 27414033 TI - Amyotrophic Lateral Sclerosis Type 20 - In Silico Analysis and Molecular Dynamics Simulation of hnRNPA1. AB - Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and lower motor neurons. 5-10% of cases are genetically inherited, including ALS type 20, which is caused by mutations in the hnRNPA1 gene. The goals of this work are to analyze the effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on hnRNPA1 protein function, to model the complete tridimensional structure of the protein using computational methods and to assess structural and functional differences between the wild type and its variants through Molecular Dynamics simulations. nsSNP, PhD-SNP, Polyphen2, SIFT, SNAP, SNPs&GO, SNPeffect and PROVEAN were used to predict the functional effects of nsSNPs. Ab initio modeling of hnRNPA1 was made using Rosetta and refined using KoBaMIN. The structure was validated by PROCHECK, Rampage, ERRAT, Verify3D, ProSA and Qmean. TM-align was used for the structural alignment. FoldIndex, DICHOT, ELM, D2P2, Disopred and DisEMBL were used to predict disordered regions within the protein. Amino acid conservation analysis was assessed by Consurf, and the molecular dynamics simulations were performed using GROMACS. Mutations D314V and D314N were predicted to increase amyloid propensity, and predicted as deleterious by at least three algorithms, while mutation N73S was predicted as neutral by all the algorithms. D314N and D314V occur in a highly conserved amino acid. The Molecular Dynamics results indicate that all mutations increase protein stability when compared to the wild type. Mutants D314N and N319S showed higher overall dimensions and accessible surface when compared to the wild type. The flexibility level of the C-terminal residues of hnRNPA1 is affected by all mutations, which may affect protein function, especially regarding the protein ability to interact with other proteins. PMID- 27414034 TI - Housing and Social Environments of African (Loxodonta africana) and Asian (Elephas maximus) Elephants in North American Zoos. AB - We evaluated 255 African (Loxodonta africana) and Asian (Elephas maximus) elephants living in 68 North American zoos over one year to quantify housing and social variables. All parameters were quantified for the both the day and the night and comparisons were made across these time periods as well as by species and sex. To assess housing, we evaluated not only total exhibit size, but also individual animals' experiences based on the time they spent in the unique environments into which the exhibits were subdivided. Variables developed to assess housing included measurements of area as a function of time (Total Space Experience), environment type (Indoor, Outdoor, In/Out Choice) and time spent on hard and soft flooring. Over the year, Total Space Experience values ranged from 1,273 square feet to 169,692 square feet, with Day values significantly greater than Night values (p<0.001). Elephants spent an average of 55.1% of their time outdoors, 28.9% indoors, and 16% in areas with a choice between being in or out. Time spent on hard flooring substrate ranged from 0% to 66.7%, with Night values significantly greater than Day (p<0.001). Social factors included number of animals functionally housed together (Social Experience) and social group characteristics such as time spent with juveniles and in mixed-sex groups. Overall Social Experience scores ranged from 1 to 11.2 and were significantly greater during the Day than at Night (p<0.001). There were few significant social or housing differences between African (N = 138) and Asian (N = 117) species or between males (N = 54) and females (N = 201). The most notable exception was Total Space Experience, with African and male elephants having larger Total Space Experience than Asian and female elephants, respectively (P-value<0.05). The housing and social variables evaluated herein have been used in a series of subsequent epidemiological analyses relating to various elephant welfare outcomes. PMID- 27414035 TI - Genetic Variants in the p14ARF/MDM2/TP53 Pathway Are Associated with the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated with Radical Resection. AB - The p14ARF/MDM2/ TP53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in the p14ARF/MDM2/TP53 pathway and prognosis in ESCC patients with radical resection. 124 ESCC patients with radical resection were included in this retrospective study and genotyped using the MassArray method. According to multivariate Cox hazard analysis and multiple testing, the TC/CC genotype of p14ARF rs3814960 was shown to be strongly related to a decreased overall survival (OS) (HR = 2.77, 95% CI: 1.33-5.75, P = 0.006, Pc = 0.030) and disease-free survival (DFS) (HR = 2.45, 95% CI: 1.30-4.61, P = 0.005, Pc = 0.025). Moreover, patients with the DEL/A +AA genotype of MDM2 rs34886328 had a notably increased OS (HR = 0.27, 95% CI: 0.13 0.56, P = 4.7*10-4, Pc = 0.003) and DFS (HR = 0.22, 95% CI: 0.11-0.43, P = 1.1*10 5, Pc = 6.6*10-5). We also found that these two SNPs had a cumulative effect on the prognosis of ESCC, with the OS (P < 0.001) and DFS (P < 0.001) being shortest for patients carrying both of these unfavorable genotypes. In conclusion, genetic variants of the p14ARF/MDM2/TP53 pathway are significantly related to OS and DFS, and may be predictors of the prognosis of ESCC after surgery. We speculate the individuals with the TC/CC genotype of p14ARF rs3814960 and/or the DEL/DEL genotype of MDMD2 rs34886328 should have more aggressive treatment and may greatly benefit from early prediction and prevention of an unfavorable prognosis by genotyping before the initiation of therapy. These findings should be further validated in a larger population. PMID- 27414036 TI - The comparative effects of diethyldithiocarbamate-copper complex with established proteasome inhibitors on expression levels of CYP1A2/3A4 and their master regulators, aryl hydrocarbon and pregnane X receptor in primary cultures of human hepatocytes. AB - In the recent years, a therapeutic potential of disulfiram (Antabuse) complex with copper, as an anticancer drug, was recognized towards several cancer cell lines. The proteasome was suggested as one of the cellular targets for this compound. As the therapeutic use of diethyldithiocarbamate-copper complex (CuET) is expected to increase, it is of great interest to know whether this compound may be the source of drug-drug interactions via the induction of biotransformation enzymes, especially cytochromes P450 (CYPs). To this purpose, we examined the effect of CuET and compared it with typical inducers (rifampicin and dioxin) of CYPs and with well-established proteasome inhibitors (MG132 and bortezomib). Diethyldithiocarbamate-copper complex revealed inconsistent and rather modulatory effect on the expression of CYP1A2 and CYP3A4 in several cultures of human hepatocytes. Moreover, it was able to cause neither ubiquitin accumulation nor significant and dose-dependent inhibition of proteasome activity. It had no effect on essential transcription factors involved in regulation of selected CYPs, aryl hydrocarbon (AhR) nor pregnane X receptor (PXR). However, the AhR protein was increased in majority of examined hepatocyte cultures. The main finding of this study is that: (i) disulfiram-copper complex is not the cause of drug-drug interactions via CYP1A2/3A4 induction; (ii) proteasome inhibitors may have different impact on studied parameters in given in vitro system. PMID- 27414037 TI - Technical Advances of the Recombinant Antibody Microarray Technology Platform for Clinical Immunoproteomics. AB - In the quest for deciphering disease-associated biomarkers, high-performing tools for multiplexed protein expression profiling of crude clinical samples will be crucial. Affinity proteomics, mainly represented by antibody-based microarrays, have during recent years been established as a proteomic tool providing unique opportunities for parallelized protein expression profiling. But despite the progress, several main technical features and assay procedures remains to be (fully) resolved. Among these issues, the handling of protein microarray data, i.e. the biostatistics parts, is one of the key features to solve. In this study, we have therefore further optimized, validated, and standardized our in-house designed recombinant antibody microarray technology platform. To this end, we addressed the main remaining technical issues (e.g. antibody quality, array production, sample labelling, and selected assay conditions) and most importantly key biostatistics subjects (e.g. array data pre-processing and biomarker panel condensation). This represents one of the first antibody array studies in which these key biostatistics subjects have been studied in detail. Here, we thus present the next generation of the recombinant antibody microarray technology platform designed for clinical immunoproteomics. PMID- 27414038 TI - Prevalence and Diversity of Salmonella Serotypes in Ecuadorian Broilers at Slaughter Age. AB - Salmonella is frequently found in poultry and represent an important source for human gastrointestinal infections worldwide. The aim of this study was to investigate the prevalence, genotypes and antimicrobial resistance of Salmonella serotypes in broilers from Ecuador. Caeca content from 388 at random selected broiler batches were collected in 6 slaughterhouses during 1 year and analyzed by the ISO 6579/Amd1 protocol for the isolation for Salmonella. Isolates were serotyped and genotypic variation was acceded by pulsed field gel electrophoresis. MIC values for sulfamethoxazole, gentamicin, ciprofloxacin, ampicillin, cefotaxime, ceftazidime, tetracycline, streptomycin, trimethropim, chloramphenicol, colistin, florfenicol, kanamycin and nalidixic acid were obtained. Presence of blaCTX-M, blaTEM, blaSHV and blaCMY; and mcr-1 plasmid genes was investigated in resistant strains to cefotaxime and colistin respectively. Prevalence at batch level was 16.0%. The most common serotype was S. Infantis (83.9%) followed by S. Enteritidis (14.5%) and S. Corvallis (1.6%). The pulsed field gel electrophoresis analysis showed that S. Corvallis, S. Enteritidis and S. Infantis isolates belonged to 1, 2 and 12 genotypes respectively. S. Infantis isolates showed high resistance rates to 12 antibiotics ranging from 57.7% (kanamycin) up to 98.1% (nalidixic acid and sulfamethoxazole). All S. Enteritidis isolates showed resistance to colistin. High multiresistant patterns were found for all the serotypes. The blaCTX-M gene was present in 33 S. Infantis isolates while mcr-1 was negative in 10 colistin resistant isolates. This study provides the first set of scientific data on prevalence and multidrug resistant Salmonella coming from commercial poultry in Ecuador. PMID- 27414039 TI - Sleep quality is associated with walking under dual-task, but not single-task performance. AB - OBJECTIVES: The objective of this study was to assess the relationship between sleep behavior and gait performance under single-task (ST) and dual-task (DT) walking conditions in community- dwelling older adults. METHODS: Walking under ST and DT conditions was evaluated in 34 community-dwelling older adults, 64.7% women, mean age 71.5 (SD+/-5.8). Gait-speed and gait-variability data were collected using the OPAL wearable sensors of the Mobility Lab. Sleep behavior (sleep efficiency [SE] and sleep latency [SL]) was assessed using actigraphy, over 5 consecutive nights. RESULTS: Lower SE was associated with decreased gait speed and increased stride-length variability during DT (rs=0.35; p=0.04; rs= 0.36; p=0.03, respectively), whereas longer SL was associated with increased stride-length variability during DT (rs=0.38; p=.03). After controlling for age and cognition, SE accounted for 24% and 33% of the variability in stride length and stride time. No associations were found between sleep and gait measures under ST walking. CONCLUSIONS: Lower SE is associated with decreased gait speed and increased gait variability under DT conditions that are indicative of an increased risk for falls in older adults. Our findings support clinical recommendations to incorporate the evaluation of sleep quality in the context of risk assessment for falls. PMID- 27414040 TI - The arm posture in children with unilateral Cerebral Palsy is mainly related to antero-posterior gait instability. AB - In this observational case-control study we aimed to determine whether altered arm postures in children with unilateral CP (uniCP) are related to gait instability in a specific direction. Antero-posterior and medio-lateral Foot Placement Estimator instability measures and arm posture measures (vertical and antero-posterior hand position, sagittal and frontal upper arm elevation angle) were determined in eleven uniCP (7 years-10 months) and twenty-four typically developing children (9 years-6 months) at two walking speeds. Spearman-rank correlation analyses were made to examine the relationship between antero posterior and medio-lateral arm posture and gait instability. Arm posture in both planes was related to antero-posterior instability (e.g. sagittal and frontal upper arm elevation angle correlated moderately with antero-posterior instability; R=0.41, p<0.001, R=-0.47, p<0.001). In uniCP, increased antero posterior instability was associated with a higher (R=-0.62, p=0.002) and more frontal position of the hemiplegic hand (R=-0.58, p=0.005), while the non hemiplegic upper arm was rotated more backward (R=0.63, p=0.002) and both upper arms rotated more sideways (hemiplegic: R=-0.58, p=0.004; non-hemiplegic: R= 0.55, p=0.008). The altered non-hemiplegic (sagittal and frontal) arm posture in uniCP may be a compensation to reduce antero-posterior gait instability. PMID- 27414042 TI - Pt-Catalyzed Synthesis of Functionalized Symmetrical and Unsymmetrical Disilazanes. AB - In nearly every total synthesis, silylating agents are employed in synthetic steps to protect sensitive functional groups. A Pt-catalyzed hydrosilylation of various unsaturated substrates to prepare novel symmetrical and unsymmetrical disilazanes is described. The developed synthetic methodology is widely applicable and tolerates all manner of functional groups (e.g., amines, ethers, esters, halogens, silanes, etc.). To demonstrate the value of the described method, mono-substituted 1,1,3,3-tetramethyldisilazanes were further selectively converted to completely new unsymmetrical derivatives. PMID- 27414041 TI - Predicting tibiotalar and subtalar joint angles from skin-marker data with dual fluoroscopy as a reference standard. AB - Evidence suggests that the tibiotalar and subtalar joints provide near six degree of-freedom (DOF) motion. Yet, kinematic models frequently assume one DOF at each of these joints. In this study, we quantified the accuracy of kinematic models to predict joint angles at the tibiotalar and subtalar joints from skin-marker data. Models included 1 or 3 DOF at each joint. Ten asymptomatic subjects, screened for deformities, performed 1.0m/s treadmill walking and a balanced, single-leg heel rise. Tibiotalar and subtalar joint angles calculated by inverse kinematics for the 1 and 3 DOF models were compared to those measured directly in vivo using dual-fluoroscopy. Results demonstrated that, for each activity, the average error in tibiotalar joint angles predicted by the 1 DOF model were significantly smaller than those predicted by the 3 DOF model for inversion/eversion and internal/external rotation. In contrast, neither model consistently demonstrated smaller errors when predicting subtalar joint angles. Additionally, neither model could accurately predict discrete angles for the tibiotalar and subtalar joints on a per-subject basis. Differences between model predictions and dual fluoroscopy measurements were highly variable across subjects, with joint angle errors in at least one rotation direction surpassing 10 degrees for 9 out of 10 subjects. Our results suggest that both the 1 and 3 DOF models can predict trends in tibiotalar joint angles on a limited basis. However, as currently implemented, neither model can predict discrete tibiotalar or subtalar joint angles for individual subjects. Inclusion of subject-specific attributes may improve the accuracy of these models. PMID- 27414043 TI - Relationship between shoulder roll and hand propulsion in the front crawl stroke. AB - This study re-evaluated the magnitude of hand propulsion (HP) in the pull and push phases of the front crawl stroke and investigated the association between the angular velocity of shoulder roll (omegaSR) and hand propulsive lift (HPL). omegaSR was computed in the plane normal to a forward direction for 16 skilled swimmers performing the front crawl stroke at a maximal sprinting pace. HP, hand propulsive drag (HPD) and HPL were determined by a dynamic pressure approach. HP and HPD in the pull phase were greater than in the push phase (P < 0.05) while HPL in the pull phase was similar to that in the push phase. Eleven swimmers out of the 16 swimmers had a significant within-swimmers correlation between omegaSR and HPL in the push phase (P < 0.05). That is, HPL increased in the push phase as the omegaSR of rolling back to the neutral position became faster. A swimmer should use more drag for hand propulsion in the pull phase and propulsion from drag and lift equally in the push phase. Based on the relationship between omegaSR and HPL in the push phase, a possible stroke technique to enhance HPL using omegaSR is discussed. PMID- 27414044 TI - Fusion of Computed Tomography and PROPELLER Diffusion-Weighted Magnetic Resonance Imaging for the Detection and Localization of Middle Ear Cholesteatoma. AB - Importance: A method to optimize imaging of cholesteatoma by combining the strengths of available modalities will improve diagnostic accuracy and help to target treatment. Objective: To assess whether fusing Periodically Rotated Overlapping Parallel Lines With Enhanced Reconstruction (PROPELLER) diffusion weighted magnetic resonance imaging (DW-MRI) with corresponding temporal bone computed tomography (CT) images could increase cholesteatoma diagnostic and localization accuracy across 6 distinct anatomical regions of the temporal bone. Design, Setting, and Participants: Case series and preliminary technology evaluation of adults with preoperative temporal bone CT and PROPELLER DW-MRI scans who underwent surgery for clinically suggested cholesteatoma at a tertiary academic hospital. When cholesteatoma was encountered surgically, the precise location was recorded in a diagram of the middle ear and mastoid. For each patient, the 3 image data sets (CT, PROPELLER DW-MRI, and CT-MRI fusion) were reviewed in random order for the presence or absence of cholesteatoma by an investigator blinded to operative findings. Main Outcomes and Measures: If cholesteatoma was deemed present on review of each imaging modality, the location of the lesion was mapped presumptively. Image analysis was then compared with surgical findings. Results: Twelve adults (5 women and 7 men; median [range] age, 45.5 [19-77] years) were included. The use of CT-MRI fusion had greater diagnostic sensitivity (0.88 vs 0.75), positive predictive value (0.88 vs 0.86), and negative predictive value (0.75 vs 0.60) than PROPELLER DW-MRI alone. Image fusion also showed increased overall localization accuracy when stratified across 6 distinct anatomical regions of the temporal bone (localization sensitivity and specificity, 0.76 and 0.98 for CT-MRI fusion vs 0.58 and 0.98 for PROPELLER DW MRI). For PROPELLER DW-MRI, there were 15 true-positive, 45 true-negative, 1 false-positive, and 11 false-negative results; overall accuracy was 0.83. For CT MRI fusion, there were 20 true-positive, 45 true-negative, 1 false-positive, and 6 false-negative results; overall accuracy was 0.90. Conclusions and Relevance: The poor anatomical spatial resolution of DW-MRI makes precise localization of cholesteatoma within the middle ear and mastoid a diagnostic challenge. This study suggests that the bony anatomic detail obtained via CT coupled with the excellent sensitivity and specificity of PROPELLER DW-MRI for cholesteatoma can improve both preoperative identification and localization of disease over DW-MRI alone. PMID- 27414045 TI - Nanostructured Silicon Used for Flexible and Mobile Electricity Generation. AB - The use of nanostructured silicon for the generation of electricity in flexible and mobile devices is reviewed. This field has attracted widespread interest in recent years due to the emergence of plastic electronics. Such developments are likely to alter the nature of power sources in the near future. For example, flexible photovoltaic cells can supply electricity to rugged and collapsible electronics, biomedical devices, and conformable solar panels that are integrated with the curved surfaces of vehicles or buildings. Here, the unique optical and electrical properties of nanostructured silicon are examined, with regard to how they can be exploited in flexible photovoltaics, thermoelectric generators, and piezoelectric devices, which serve as power generators. Particular emphasis is placed on organic-silicon heterojunction photovoltaic devices, silicon-nanowire based thermoelectric generators, and core-shell silicon/silicon oxide nanowire based piezoelectric devices, because they are flexible, lightweight, and portable. PMID- 27414046 TI - Immunoglobulin a nephropathy: Pathological markers of renal survival in paediatric patients. AB - IgA nephropathy (IgAN) is one of the leading causes of glomerulonephritis characterized by the findings of IgA and IgG immune deposits in the mesangium of kidney biopsies from patients with persistent microscopic haematuria. IgAN is frequently detected among adolescents and young adults. IgAN presents a highly variable course that includes a spectrum from a very mild disease to end-stage renal disease (ESRD). There are several clinical and histological factors that strongly determined the final outcome of patients with IgAN. Pathological variables associated with unfavorable outcomes are mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and interstitial fibrosis/tubular atrophy, according to the Oxford classification. Moreover, some studies also suggest a role for complement activation in the pathogenesis of IgAN. In this regard, staining for C4d may be an independent risk factor for the development of ESRD in IgAN. Despite the growing number of studies assessing IgAN risk factors, this kind of investigation in paediatric patients is still very limited. The aim of this article is to revise pathological markers related to deterioration of renal function in paediatric patients with IgAN, particularly those that can independently affect renal survival. PMID- 27414049 TI - The Unbearable Weight on Your Mind: The Physiological Dimension of Body Image Disturbances. AB - The ideal body, according to Western society's standards of physical appearance, has become increasingly thinner. Body image disturbances, a phenomenon often associated with today's society's standards of thinness, are common among obese and eating-disordered subjects, and have recently been documented in normal weight subjects. The aim of this review is to propose a new biological interpretation of body image disturbances, not presenting them as a mere consequence of society's pressure to be thin, but as a result of body weight regulation. Early in life, a "set-point-related body image" that may be described as a schematized representation of one's body weight set-point, would be created by the central nervous system. This unconscious representation of one's body size and mass, would later act as an internal reference in processing weight relevant information. External cues concerning body weight (e.g. visual information regarding one's body shape) as well as internal cues (e.g. moving one's body against gravity) would both be compared, by the central nervous system, to the set-point-related body image. A difference between actual body size and setpoint related body image could generate an "error signal" that would lead to body image disturbances. These disturbances, reflecting the error signal of the regulatory system, would in turn trigger corrective metabolic and behavioral mechanisms working to return body weight to set-point. PMID- 27414048 TI - Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome. AB - Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology. PMID- 27414050 TI - Interactive Effects of Neurochemicals on Ingestive Behavior. AB - Most previous research has focused on the effects of single neurotransmitters and neuropeptides on ingestive behavior. An important next step in the advancement of the science of ingestive behavior is to gain an understanding of how these different systems interact with one another. The present article is designed as an introduction to interacting systems involved in the regulation of food intake. Specifically, we review recent research on several neurochemicals that have emerged as good candidates for further study of interactions because they appear to serve integrative roles. PMID- 27414047 TI - Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc. AB - Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses. PMID- 27414051 TI - Vitamin A Deficiency Decreases the Expression of RARbeta and RXRbeta/gamma in Adult Mouse Brain: Effect of RA Administration. AB - Recent studies have revealed a novel and unexpected role of vitamin A, via its nuclear receptors, in higher cognitive functions. We examined, in mouse brain, the impact of vitamin A status on the level of retinoic acid nuclear receptor (RAR and RXR) expression and on one of their responsive genes, that of the tissue transglutaminase (tTG). Weanling male C57B1/6 mice fed a vitamin A deficient diet developed a vitamin A deficiency which was characterized, after 26 weeks, by the depletion of serum retinol, liver retinol and retinyl palmitate, and by the decreased activity of liver tTG. After 27 weeks of the diet, the vitamin A depleted mice exhibited a significantly lower amount of brain RAR beta and RXR beta/gamma mRNA relative to control mice. Vitamin A deficiency also resulted in a reduced expression of tTG. When 35-week depleted mice were subsequently administrated RA for 28 days, the expression of RA nuclear receptors and tTG was significantly induced. The vitamin A deficiency mouse model and repletion provides a physiological system for monitoring the effects of vitamin A status on gene expression and on neurobiological processes in the adult brain. PMID- 27414052 TI - Interactions of Glucocorticoids, NPY and Hypothalamic Serotonin. AB - Neuropeptide Y (NPY), insulin, corticosterone (CORT) and 5-hydroxytryptamine (5 HT), or serotonin, are all involved in energy homeostasis. To show how they might interact, the effects of NPY on plasma insulin and on 5-HT metabolism in the paraventricular hypothalamic nucleus (PVN), the ventromedial hypothalamic nucleus (VMN), the arcuate nucleus (ARC), and the locus coeruleus (LC) were measured in separate groups of intact, adrenalectomized (ADX), or ADX and CORT replaced Sprague-Dawley rats. Fifteen minutes after ICV injection of NPY, no effect on 5 HT metabolism in the intact animal was observed. 5-HT and its metabolite, 5-HIAA, increased in the PVN as a result of ADX, an effect that was reversed with CORT replacement. NPY also reversed these effects. Similar effects of ADX, CORT replacement and NPY were noted with 5-HIAA in the ARC. This suggests a role for 5 HT in the attenuation of weight gain in ADX animals. NPY also caused an increase in plasma insulin in the CORT replaced animal, but not the intact animal. This was most likely due to an inability of CORT replaced animals to adjust their CORT levels in response to NPY. PMID- 27414053 TI - A Diet Enriched in alpha-Lipoic Acid Reverses the Age-Related Compromise in Antioxidant Defences in Rat Cortical Tissue. AB - In this study we set out to establish whether age-related changes in reactive oxygen species production in cortical tissue might be modulated by a diet enriched in the proposed antioxidant, alpha-lipoic acid. Twenty-two month-old and 4 month-old rats were fed on control diet or alpha-lipoic acid-enriched diet for 2 months. We report that cortical tissue prepared from rats fed on control diet revealed an age-related increase in reactive oxygen species production, which was accompanied by an increase in activity of superoxide dismutase activity and decreases in activities of glutathione peroxidase and catalase. These changes were attenuated in rats fed on the experimental diet. There was an age-related increase in the concentration of interleukin-1beta (IL-1beta), which was reversed by dietary manipulation. IL-1beta increased reactive oxygen species production in vitro, suggesting that it may also exert this effect in vivo. We observed an age related increase in lipid peroxidation accompanied by a decrease in arachidonic acid concentration and suggest that these changes are a consequence of increased reactive oxygen species production. Dietary manipulation with alpha-lipoic acid reverses the age-related changes in activities of superoxide dismutase, catalase and glutathione peroxidase and accumulation of reactive oxygen species production adding support to the hypothesis that alpha-lipoic acid exerts antioxidant effects. PMID- 27414054 TI - Postnatal Stress in Mice: Effects on Body Fat, Plasma Lipids, Glucose and Insulin. AB - Mice pups were exposed to stressful stimuli everyday during the first 3 weeks of life. Body weight, food intake and spontaneous locomotor activity, triglycerides, cholesterol, phospholipids, glucose and insulin basal levels, as well as epididymal fat pad weight and its cell volume were measured in stressed and control animals. Results indicated that postnatal stressful manipulations induced an increase in body weight, epididymal fat pad weight and its cell volume, as well as in insulin, glucose, cholesterol and triglycerides plasma levels, at 4 months of age. No significant changes in food consumption, locomotor activity and phospholipids plasma levels were found. Present data suggest that early stressful manipulations may induce residual effects on lipid and glucid metabolism. PMID- 27414056 TI - Associations between school violence, military connection, and gang membership in California secondary schools. AB - Recent studies have found that military-connected students confront many challenges-such as secondary traumatization-that may stem from a parent's deployment and frequent relocations. It is possible that multiple moves and deployments of family service members are associated with military-connected students' gang membership and involvement with school violence behaviors. In this study, a total of 13,484 students completed the core and military modules of the California Healthy Kids Survey. Logistic regressions examined the odds of a student being a member of a gang given their grade, gender, race/ethnicity, school violence behaviors, military-connectedness, changes in schools, and familial deployments. Results indicated that of the nearly 8% of students sampled who reported being in a gang, those with a parent or sibling currently serving in the military reported a higher prevalence rate of gang membership than students with no military connection. Students who reported being in fights or carrying weapons to school were at least twice more likely to be a gang member than students who reported not having been in fights or carrying weapons. Changing schools 4 or more times in a 5-year period and experiencing at least 1 familial deployment were also associated with an increased likelihood of gang membership. The findings of this study offer incentive to further explicate the gang and school violence experiences of military-connected students. This study supports schools in understanding the characteristics of the military-connected students and families they serve so they can implement appropriate interventions to curb gang and school violence behaviors. (PsycINFO Database Record PMID- 27414055 TI - Mammillary body volume abnormalities in anorexia nervosa. AB - OBJECTIVE: Several case reports of Wernicke's Encephalopathy in anorexia nervosa (AN) caused by thiamine deficiency have described mammillary body (MB) injury, but systematic studies are lacking. Here we evaluated whether underweight and weight-restored individuals with AN demonstrate evidence of abnormal MB morphology, via retrospective examination of a previously collected data set. METHOD: Using standard-resolution T1-weighted magnetic resonance imaging at 3 Tesla, we measured MB volume and fornix area in a cross-sectional study of 12 underweight AN, 20 weight-restored AN, and 30 age- and sex-matched healthy comparisons. Because of the small size of these structures, a manual tracing approach was necessary to obtain accurate measurements. A blinded expert rater manually traced MB and fornix structures in each participant. RESULTS: We observed significantly smaller MB volumes in the underweight AN group. However, the weight-restored AN group exhibited significantly larger MB volumes. The right fornix was smaller in the weight-restored AN group only. DISCUSSION: These findings suggest the possibility that MB volume and fornix area could represent potential biomarkers of acute weight loss and restoration, respectively. Verification of this finding through prospective studies evaluating MB morphology, cognition, and thiamine levels longitudinally across individual illness trajectories might be warranted. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:920-929). PMID- 27414057 TI - Profiles of youth in therapeutic group care: Associations with involuntary psychiatric examinations and readmissions. AB - The study aims were to identify distinct subgroups among youth placed in therapeutic group care (TGC) and to examine the effect of specific constellations of risk factors on readmission to residential mental health care and involuntary psychiatric examination among youth in TGC. Several administrative databases were merged to examine outcomes for youth placed in TGC during fiscal year FY04-05 through FY07-08 (N = 1,009). Latent class analysis (LCA) was conducted. Two classes were identified: youth with multiple needs (Class 1) and lower risk youth (Class 2). Class 1 represented 45% of youth in TGC. Compared with Class 2, these youth had a greater probability of having physical health problems, parents with substance abuse problems, and more extensive histories of maltreatment. Compared with Class 2, youth with multiple needs were almost twice more likely to exhibit self-injurious behavior leading to involuntary mental health examinations, but they were less likely to be readmitted to a residential mental health care of higher level of restrictiveness, such as state inpatient psychiatric programs (SIPPs). Youth placed in Florida TGC represent a heterogeneous population and services tailored to these youth's needs are important. Youth with multiple risk factors would benefit from interventions that would address multiple areas of risk. Lower risk youth (Class 2) would benefit from interventions that would focus on promoting mental health, especially among those who have experienced threatened harm, and providing services and supports necessary for stabilizing these youth in the community. (PsycINFO Database Record PMID- 27414058 TI - [Legal Analysis of the Implementation Rules of Delegation of Home Visits by Family Doctors to Non-Physician Health Professionals: Is the Implementation in Accordance with the Intention of the Law?] AB - Objective: Triggered by the AGnES model project of the University Medicine Greifswald, the Code of Social Law V was changed by the German Lower and Upper House of Parliament (Bundestag and Bundesrat) in 2008 so that the delegation of GP's activities to non-physician colleagues was allowed under highly restricted preconditions. Delegated home visits should become an integral part of the standard care in Germany. In this study, the implementation of S 87 para 2b clause 5 SGB V, established in Annex 8 of the Federal Collective Agreement, was checked for its legality in terms of qualification. Methods: The problem was checked with the legal methods of interpretation in pursuance of the norm and the methods of systematic, historic and teleologic interpretation. Results: Even though the Parliament clearly required orientation to the AGnES model project (in order to assure safety and effective care of delegated home visits), self management in the implementation of the law remained far behind these guidelines. The main outcome of the legal analysis was that the implementation arrangements of the Code of Social Law V are predominantly illegal. Conclusions: The parties of the Federal Collective Agreement have to change the arrangements to meet the requirements of the Parliament and to avoid risks of liability for delegating GPs. PMID- 27414059 TI - The prevalence of pre-existing mental health, drug and alcohol conditions in major trauma patients. AB - Objective Capturing information about mental health, drug and alcohol conditions in injury datasets is important for improving understanding of injury risk and outcome. This study describes the prevalence of pre-existing mental health, drug and alcohol conditions in major trauma patients based on routine discharge data coding. Methods Data were extracted from the population-based Victorian State Trauma Registry (July 2005 to June 2013, n=16096). Results Seventeen percent of major trauma patients had at least one mental health condition compared with the Australian population prevalence of 21%. The prevalence of mental health conditions was similar to the Australian population prevalence in men (19% v. 18%), but lower in women (14% v. 25%) and across all age groups. Mental health conditions were more prevalent in intentional self-harm cases (56.3%) compared with unintentional (13.8%) or other intentional (31.2%) cases. Substance use disorders were more prevalent in major trauma patients than the general population (15% v. 5%), higher in men than women (17% v. 10%) and was highest in young people aged 25-34 years (24%). Conclusions Under-reporting of mental health conditions in hospital discharge data appears likely, reducing the capacity to characterise the injury population. Further validation is needed. What is known about the topic? Medical record review, routine hospital discharge data and self report have been used by studies previously to characterise mental health, drug and alcohol conditions in injured populations, with medical record review considered the most accurate and reliance on self-report measures being considered at risk of recall bias. The use of routinely collected data sources provides an efficient and standardised method of characterising pre-existing conditions, but may underestimate the true prevalence of conditions. What does this paper add? No study to date has explored the prevalence of Abbreviated Injury Scale and International Classification of Diseases and Health Related Problems, Tenth Revision, Australian Modification (ICD-10-a.m)-coded mental health, alcohol and drug conditions in seriously injured populations. The results of this study show the incidence of mental health conditions appeared to be under reported in major trauma patients, suggesting limitations in the use of ICD-10 a.m. to measure mental health comorbidities. What are the implications for practitioners? In order to achieve improvements in measuring mental health, drug and alcohol comorbidities, we suggest the use of a series of different diagnostic systems to be used in conjunction with ICD-10-a.m., such as medical record review and self-reporting as well as linkage to other datasets. When applied simultaneously, diagnosis and outcomes of mental health may be compared and validated across diagnostic systems and deviations in diagnoses could be more readily accounted for. PMID- 27414061 TI - Auditory and verbal memory predictors of spoken language skills in children with cochlear implants. AB - BACKGROUND: Large variability in individual spoken language outcomes remains a persistent finding in the group of children with cochlear implants (CIs), particularly in their grammatical development. AIMS: In the present study, we examined the extent of delay in lexical and morphosyntactic spoken language levels of children with CIs as compared to those of a normative sample of age matched children with normal hearing. Furthermore, the predictive value of auditory and verbal memory factors in the spoken language performance of implanted children was analyzed. METHODS & PROCEDURES: Thirty-nine profoundly deaf children with CIs were assessed using a test battery including measures of lexical, grammatical, auditory and verbal memory tests. Furthermore, child related demographic characteristics were taken into account. OUTCOMES & RESULTS: The majority of the children with CIs did not reach age-equivalent lexical and morphosyntactic language skills. Multiple linear regression analyses revealed that lexical spoken language performance in children with CIs was best predicted by age at testing, phoneme perception, and auditory word closure. The morphosyntactic language outcomes of the CI group were best predicted by lexicon, auditory word closure, and auditory memory for words. CONCLUSIONS: Qualitatively good speech perception skills appear to be crucial for lexical and grammatical development in children with CIs. Furthermore, strongly developed vocabulary skills and verbal memory abilities predict morphosyntactic language skills. PMID- 27414060 TI - Analysis of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-reactive CD8(+) T cell responses in children with NPM-ALK(+) anaplastic large cell lymphoma. AB - Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8(+) T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8(+) T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM-ALK were used as antigen-presenting cells for T cell stimulation. Responder T lymphocytes were tested in interferon-gamma enzyme linked immunospot (ELISPOT) assays with NPM-ALK-transfected autologous DCs as well as CV-1 in Origin with SV40 genes (COS-7) cells co-transfected with genes encoding the patients' HLA class I alleles and with NPM-ALK encoding cDNA to verify responses and define the HLA restrictions of specific T cell responses. NPM-ALK-specific CD8(+) T cell responses were detected in three of five ALK positive ALCL patients tested between 1 and 13 years after diagnosis. The three patients had also maintained anti-ALK antibody responses. No reactivity was detected in samples from five healthy donors. The NPM-ALK-specific CD8(+) T cell responses were restricted by HLA-C-alleles (C*06:02 and C*12:02) in all three cases. This approach allowed for the detection of NPM-ALK-reactive T cells, irrespective of the individual HLA status, up to 9 years after ALCL diagnosis. PMID- 27414062 TI - Improved Deconvolution of Protein Targets for Bioactive Compounds Using a Palladium Cleavable Chloroalkane Capture Tag. AB - The benefits provided by phenotypic screening of compound libraries are often countered by difficulties in identifying the underlying cellular targets. We recently described a new approach utilizing a chloroalkane capture tag, which can be chemically attached to bioactive compounds to facilitate the isolation of their respective targets for subsequent identification by mass spectrometry. The tag minimally affects compound potency and membrane permeability, enabling target engagement inside cells. Effective enrichment of these targets is achieved through selectivity in both their rapid capture onto immobilized HaloTag and their subsequent release by competitive elution. Here, we describe a significant improvement to this method where selective elution was achieved through palladium catalyzed cleavage of an allyl-carbamate linkage incorporated into the chloroalkane capture tag. Selective tag cleavage provided robust release of captured targets exhibiting different modes of binding to the bioactive compound, including prolonged residence time and covalent interactions. Using the kinase inhibitors ibrutinib and BIRB796 as model compounds, we demonstrated the capability of this new method to identify both expected targets and "off-targets" exhibiting a range of binding affinities, cellular abundances, and binding characteristics. PMID- 27414063 TI - Velocity Fluctuations in Kinesin-1 Gliding Motility Assays Originate in Motor Attachment Geometry Variations. AB - Motor proteins such as myosin and kinesin play a major role in cellular cargo transport, muscle contraction, cell division, and engineered nanodevices. Quantifying the collective behavior of coupled motors is critical to our understanding of these systems. An excellent model system is the gliding motility assay, where hundreds of surface-adhered motors propel one cytoskeletal filament such as an actin filament or a microtubule. The filament motion can be observed using fluorescence microscopy, revealing fluctuations in gliding velocity. These velocity fluctuations have been previously quantified by a motional diffusion coefficient, which Sekimoto and Tawada explained as arising from the addition and removal of motors from the linear array of motors propelling the filament as it advances, assuming that different motors are not equally efficient in their force generation. A computational model of kinesin head diffusion and binding to the microtubule allowed us to quantify the heterogeneity of motor efficiency arising from the combination of anharmonic tail stiffness and varying attachment geometries assuming random motor locations on the surface and an absence of coordination between motors. Knowledge of the heterogeneity allows the calculation of the proportionality constant between the motional diffusion coefficient and the motor density. The calculated value (0.3) is within a standard error of our measurements of the motional diffusion coefficient on surfaces with varying motor densities calibrated by landing rate experiments. This allowed us to quantify the loss in efficiency of coupled molecular motors arising from heterogeneity in the attachment geometry. PMID- 27414064 TI - Polymorphic Crystallization and Crystalline Reorganization of Poly(l-lactic acid)/Poly(d-lactic acid) Racemic Mixture Influenced by Blending with Poly(vinylidene fluoride). AB - The effects of poly(vinylidene fluoride) (PVDF) on the crystallization kinetics, competing formations of homocrystallites (HCs) and stereocomplexes (SCs), polymorphic crystalline structure, and HC-to-SC crystalline reorganization of the poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic mixture were investigated. Even though the PLLA/PDLA/PVDF blends are immiscible, blending with PVDF enhances the crystallization rate and SC formation of PLLA/PDLA components at different temperatures that are higher or lower than the melting temperature of the PVDF component; it also facilitates the HC-to-SC melt reorganization upon heating. The crystallization rate and degree of SC crystallinity (Xc,SC) of PLLA/PDLA components in nonisothermal crystallization increase after immiscible blending with PVDF. At different isothermal crystallization temperatures, the crystallization half-time of PLLA/PDLA components decreases; its spherulitic growth rate and Xc,SC increase as the mass fraction of PVDF increases from 0 to 0.5 in the presence of either a solidified or a molten PVDF phase. The HCs formed in primary crystallization of PLLA/PDLA components melt and recrystallize into SCs upon heating; the HC-to-SC melt reorganization is promoted after blending with PVDF. We proposed that the PVDF-promoted crystallization, SC formation, and HC-to-SC melt reorganization of PLLA/PDLA components in PLLA/PDLA/PVDF blends stem from the enhanced diffusion ability of PLLA and PDLA chains. PMID- 27414065 TI - Mechanically Shaped Two-Dimensional Covalent Organic Frameworks Reveal Crystallographic Alignment and Fast Li-Ion Conductivity. AB - Covalent organic frameworks (COFs) usually crystallize as insoluble powders, and their processing for suitable devices is thought to be limited. We demonstrate that COFs can be mechanically pressed into shaped objects having anisotropic ordering with preferred orientation between hk0 and 00l crystallographic planes. Five COFs with different functionality and symmetry exhibited similar crystallographic behavior and remarkable stability, indicating the generality of this processing. Pellets prepared from bulk COF powders impregnated with LiClO4 displayed room temperature conductivity up to 0.26 mS cm(-1) and high electrochemical stability. This outcome portends use of COFs as solid-state electrolytes in batteries. PMID- 27414066 TI - Enabling a High Performance of Mesoporous alpha-Fe2O3 Anodes by Building a Conformal Coating of Cyclized-PAN Network. AB - The mesoporous alpha-Fe2O3/cyclized-polyacrylonitrile (C-PAN) composite was synthesized by a rapid and facile two-step method. The electrode was fabricated without conductive carbon addictive and employed as anode for lithium-ion batteries. Results demonstrate that building a conformal coating of a C-PAN network can provide a strong adhesion with active materials and contribute excellent electronic conductivity to the electrode, which can relieve the huge volume changes during a lithiation/delithiation process and accelerate the charge transfer rate. The material exhibited high reversible capacity of ca. 996 mAh g( 1) after 100 cycles at 0.2C, 773 mAh g(-1) at 1C and 655 mAh g(-1) at 2C, respectively, showing well-enhanced cycling performance and superior rate capacity, and also exhibiting significantly improved power density and energy density compared to the traditional graphite materials. Our results provide a facile and efficient way to enhance the performance of alpha-Fe2O3 anode material, which also can be applied for other oxide anode materials. PMID- 27414067 TI - Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer. AB - In addition to each of the factors that govern the identification of a successful oncology drug candidate, drug discovery aimed at treating neurological cancer must also consider the presence of the blood-brain barrier (BBB). The high level of expression of efflux transporters (e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp)) at the BBB limits many small molecules from freely reaching the brain, where neurooncologic malignancies reside. Furthermore, many of the targets identified for the potential treatment of central nervous system (CNS) malignancies suggest that kinase inhibitors, capable of penetrating the BBB to reach their target, would be desirable. This Perspective discusses the unmet need for neurooncology treatments, the appeal of kinase targets in this space, and a summary of what is known about free brain penetration of clinical inhibitors of kinases that are of interest for the treatment of brain cancer. PMID- 27414068 TI - Notes from the Field: Meningococcal Disease in an International Traveler on Eculizumab Therapy - United States, 2015. AB - On June 2, 2015, CDC was notified that a male airline passenger, aged 41 years, with a fever of 105.4 degrees F, headache, nausea, photophobia, diarrhea, and vomiting, which began approximately 3 hours after departure, was arriving to San Francisco, California, on a flight from Frankfurt, Germany. His symptoms reportedly started with neck stiffness 1 day earlier. Upon arrival, the patient was immediately transported to a local hospital, where he was in septic shock, which was followed by multisystem organ failure. Cerebrospinal fluid, obtained approximately 12 hours after initiation of treatment, was Gram stain- and culture negative. Blood cultures, which were drawn before antibiotic treatment, were positive for Neisseria meningitides of indeterminate serogroup. A review of the patient's medical records revealed a history of paroxysmal nocturnal hemoglobinuria and current biweekly eculizumab (Soliris) therapy. PMID- 27414069 TI - ABiO2X (A = Cd, Ca, Sr, Ba, Pb; X = halogen) Sillen X1 Series: Polymorphism Versus Optical Properties. AB - The Sillen X1 series of Bi(3+)A(2+)O2X (A = Cd, Ca, Sr, Ba, Pb; X = Cl, Br, I) compounds is composed of three main crystallographic types, namely, the tetragonal form (space group (S.G.) I4/mmm), the orthorhombic form (S.G. Cmcm), and the monoclinic form (S.G. P21/m). Because of Bi(3+)/A(2+) disorder the Bi(3+) based photoluminescence (PL) of the tetragonal polytypes is quenched at room temperature (RT). In the two other ordered forms, the Bi-O-Bi connectivity is different but limited, such that bluish/greenish emission occurs at RT in the monoclinic CdBiO2Cl and CaBiO2Cl and orthorhombic SrBiO2Cl and BaBiO2Cl phases. The crystal structure of BaBiO2Br was refined in the orthorhombic Cmcm space group and also shows RT emission. Focusing on the RT luminescent activity as a key parameter, the PL active compounds were investigated by means of density functional theory calculations and UV-visible reflectance spectroscopy. The influence of A and X ions on the excitation energy is discussed by analyzing the A-O-Bi and Bi-X bonding schemes and gives some insights for rational tuning of both the excitation and emission energies. PMID- 27414070 TI - Serum adenosine deaminase, catalase, and carbonic anhydrase activities in patients with renal cell carcinoma. AB - OBJECTIVES: To determine whether serum levels of adenosine deaminase (AD), catalase (CAT), and carbonic anhydrase (CA) enzymes may be useful biomarkers in the diagnosis of renal tumors and may lead to early diagnosis of renal tumors. MATERIAL AND METHODS: The study included 33 patients with renal cell carcinoma (RCC) and 31 healthy controls. The activity of serum AD, CA, and CAT was determined and analyzed using the Giusti spectrophotometric method, H2O2 substrate, and C02 hydration, respectively. RESULTS: Serum AD and CA activity were significantly higher in patients with RCC than in controls. However, serum CAT activity was significantly lower in patients with RCC than in controls. CONCLUSION: These markers might be potentially important as an additional biochemical tool for diagnosing RCC. We believe multidisciplinary studies are needed to plan patients' preoperative and postoperative treatment and to create follow-up protocols. PMID- 27414071 TI - Carrier Delocalization in Two-Dimensional Coplanar p-n Junctions of Graphene and Metal Dichalcogenides. AB - With the lateral coplanar heterojunctions of two-dimensional monolayer materials turning into reality, the quantitative understanding of their electronic, electrostatic, doping, and scaling properties becomes imperative. In contrast to traditional bulk 3D junctions where carrier equilibrium is reached through local charge redistribution, a highly nonlocalized charge transfer (trailing off as 1/x away from the interface) is present in lateral 2D junctions, increasing the junction size considerably. The depletion width scales as p(-1), while the differential capacitance varies very little with the doping level p. The properties of lateral 2D junctions are further quantified through numerical analysis of realistic materials, with graphene, MoS2, and their hybrid serving as examples. Careful analysis of the built-in potential profile shows strong reduction of Fermi level pinning, suggesting better control of the barrier in 2D metal-semiconductor junctions. PMID- 27414072 TI - Nanomaterial and toxicity: what can proteomics tell us about the nanotoxicology? AB - 1. In the last few years, a substantial scientific work is focused to identify the potential toxicity of nanomaterials by studying the cellular pathways under in vitro and in vivo conditions. Owing to high surface area to volume ratio nanoparticles (NPs) can pass through cell membranes which might be responsible for creating adverse interactions in biological systems. Simultaneously, researchers are also interested to assess the fate of NP inside the living system, which may lead to altered protein expression as well as protein corona formation. 2. According to published reports, NP-mediated toxicity involves altered cellular system including cell morphology, cell differentiation, cell metabolism, cell mobility, cellular immunity, which is derived from the side effects of nanoformulation and leading to apoptosis and necrosis. These results indicate the existence of potential toxic effect of these particles to human health. 3. The advent of proteomics with sophisticated technical improvement coupled with advanced bioinformatics has led to identify altered proteins due to nanomaterial exposure that could provide a new avenue to biomarker discovery. 4. This review aims to provide the current status of safe production and use of nanomaterials. PMID- 27414073 TI - Virulence profile: Hinh Ly. PMID- 27414075 TI - Editorial: Frontiers in Clinical Neuropsychology. PMID- 27414074 TI - Light-load maximal lifting velocity full squat training program improves important physical and skill characteristics in futsal players. AB - This study aimed to compare the effect of 6 weeks of resistance training or combined resistance training and change of direction exercises on physical performance and motor skills in futsal players. Thirty-four futsal players were divided into full squat group (SG, n = 12), combined full squat and change of direction exercises group (S+CDG, n = 12) and control group (CG, n = 10). The resistance training for SG consisted of full squat with low load (~45-58% 1RM) and low volume (4-6 repetitions), whereas the S+CDG performed the same resistance training program combined with loaded change of direction. Sprint time in 10 and 20 m, change of direction test, countermovement vertical jump (CMJ) height, maximal strength and force-velocity relationship in full squat exercise, kicking speed ball (BSmean) and repeated sprint ability (RSAmean) were selected as testing variables. Both experimental groups showed significant improvements for CMJ, BSmean and all strength parameters. Only SG resulted in significant sprint gains, whereas S+CDG also achieved significant improvements in RSAmean. The CG remained unchanged after training period. No significant differences were found between both experimental groups. These findings suggest that only 12 sessions of either lightweight resistance training alone, lifting the load at maximal intended velocity or combined with change of direction exercises is enough to improve several physical and skills capacities critical to futsal performance in adult players. PMID- 27414077 TI - Treatment of von Willebrand Disease. AB - The general goal of therapy in von Willebrand disease is to correct the two defects that are related to the bleeding tendency of these patients, i.e., the abnormal primary hemostasis expressed by a prolonged bleeding time (BT) and the abnormal intrinsic coagulation due to low factor VIII (FVIII) levels. There are two main treatments in von Willebrand disease, i.e., desmopressin and transfusional therapy with blood products. Desmopressin is most effective in patients with type 1, who account for about 80 per cent of all patients. The remaining patients with type 2 and type 3 von Willebrand disease do not respond consistently to desmopressin and need the infusion of blood products containing FVIII and von Willebrand factor. Virally-inactivated concentrates that are currently on the market are preferable to fresh-frozen plasma and cryoprecipate, that still carry a small risk of transmitting blood-borne infections. In rare instance, particularly for hemorrhoages in mucosal tracts such as gastrointestinal bleeding, platelet concentrates are useful adjuncts to plasma concentrates when patients do not respond to the latters. The role of purified von Willebrand factor and of recombinant products is still unclear. PMID- 27414076 TI - Fragile X-associated tremor/ataxia syndrome: phenotypic comparisons with other movement disorders. AB - OBJECTIVE: The purpose of this paper is to review the typical cognitive and motor impairments seen in fragile X-associated tremor/ataxia syndrome (FXTAS), essential tremor (ET), Parkinson disease (PD), spinocerebellar ataxias (SCAs), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in order to enhance diagnosis of FXTAS patients. METHODS: We compared the cognitive and motor phenotypes of FXTAS with each of these other movement disorders. Relevant neuropathological and neuroimaging findings are also reviewed. Finally, we describe the differences in age of onset, disease severity, progression rates, and average lifespan in FXTAS compared to ET, PD, SCAs, MSA, and PSP. We conclude with a flow chart algorithm to guide the clinician in the differential diagnosis of FXTAS. RESULTS: By comparing the cognitive and motor phenotypes of FXTAS with the phenotypes of ET, PD, SCAs, MSA, and PSP we have clarified potential symptom overlap while elucidating factors that make these disorders unique from one another. In summary, the clinician should consider a FXTAS diagnosis and testing for the Fragile X mental retardation 1 (FMR1) gene premutation if a patient over the age of 50 (1) presents with cerebellar ataxia and/or intention tremor with mild parkinsonism, (2) has the middle cerebellar peduncle (MCP) sign, global cerebellar and cerebral atrophy, and/or subcortical white matter lesions on MRI, or (3) has a family history of fragile X related disorders, intellectual disability, autism, premature ovarian failure and has neurological signs consistent with FXTAS. Peripheral neuropathy, executive function deficits, anxiety, or depression are supportive of the diagnosis. CONCLUSIONS: Distinct profiles in the cognitive and motor domains between these movement disorders may guide practitioners in the differential diagnosis process and ultimately lead to better medical management of FXTAS patients. PMID- 27414078 TI - Expression of Factor IX cDNA Introduced into Human Marrow Stromal Cells by Electroporation. AB - Management of hemophilia B with gene therapy is an attractive and potentially feasible goal since stringent regulation of the recombinant protein is not required and low circulating levels may be sufficient to prevent symptoms. We are investigating the potential of gene transfer by electroporation for a role in human gene therapy. In this study, we used electroporation to physically co transfer human factor IX cDNA under the influence of the potent human CMV-IE promoter and a second plasmid containing a neomycin resistance gene into human bone marrow stromal cells. Following electroporation, stromal cells were selected for neomycin resistance as co-transfection of both plasmids into the cells was expected from the results of previous studies. Analysis of genomic DNA from transfected stromal cells showed stable integration of factor IX cDNA at several sites in the genome. Following electroporation, the stromal cells were shown to secrete factor IX for three weeks in culture at a maximum concentration of 17ng/10(6) cells/day. As is the case with normal, functionally active, endogenous factor IX, the glutamic acid residues in the Gla domain of the factor IX protein were found to be post-translationally modified. Our results demonstrate the feasibility of gene transfer by electroporation and the successful post translational modification and secretion of the human factor IX protein by stromal cells. This study provides evidence of the feasibility of electroporation and the use of stromal cells for the potential correction of hemophilia B in human gene therapy. PMID- 27414079 TI - The Role of Allogeneic Transplantation in the Treatment of Multiple Myeloma. AB - In multiple myeloma (MM) attempts to improve upon the results of standard melphalanpredisone with other conventional dose drug combinations, have generally been unsuccessful, producing only minor improvements in response rate, with little effect on survival. The only treatment capable of producing a dramatic change in response and life expectancy is high-dose chemo-radiotherapy followed by stem cell transplantation. However, after autologous transplant relapse will almost inevitably occur, and freedom from recurrence curves show no plateau in most studies. Besides the resistance of the disease to chemotherapy, another possible explanation is tumor contamination of the graft. This is one major advantage of allogeneic transplantation over autologous, the other being an immune mediated mechanism of tumor suppression in part related to GVHD. Application of allogeneic transplantation to MM has met a number of obstacles, but is now entering a phase of reappraisal, due in part to a tendency to earlier transplantation, in part to the use of novel technologies such as allogeneic peripheral blood stem cells instead of marrow. The goal should be the reduction of transplant related deaths, to better exploit the higher eradication potential of allogeneic cell therapies. The most intriguing perspectives are those related to immune manipulation of recipient and/or donor. PMID- 27414080 TI - Co-expression of B7-1 with Interleukin-12 Enhances Vaccine-induced Antitumour Immunity in Experimental Myeloma. AB - There has been little improvement in the treatment of multiple myeloma over the past 25 years. Disease inevitably reoccurs in patients who receive chemotherapy of melphalan and prednisone or combinations of alkylating agents. Autologous hematopoietic stem cell transplantation can increase remission rates and prolong diseasefree and overall survival. However, all transplanted myeloma patients ultimately relapse. The ineffectiveness of conventional induction and maintenance therapies in multiple myeloma has motivated the search for alternative treatment strategies. Immunotherapy involving cancer vaccines is one such alternative where the intent is to induce a host antitumour immune response. In this study, we employed a syngeneic murine model of multiple myeloma developed in our laboratory to examine the consequence of combined expression of interleukin-12 (IL-12) and the B7-1 costimulatory molecule on myeloma immuno genicity. We show that the IL 12/B7-1 immunogene combination was efficacious in evoking systemic protective immunity against unmodified parental myeloma cells. These findings suggest that autologous myeloma cells engineered to co-express IL-12 and B7-1 may hold promise as cancer vaccines for consolidation therapy in multiple myeloma. PMID- 27414081 TI - Myeloma Presenting with Massive Splenomegaly. AB - Myeloma typically presents with skeletal damage, renal failure, metabolic disturbances and anaemia. Less usual associations are polyneuropathy, solitary plasmacytomas, and only rarely is lymphadenopathy found. Discomfort and left upper quadrant pain due to marked splenomegaly appears unknown, particularly as the initial symptom. Accordingly, two cases are reported in which this was the reason for seeking medical attention. In both splenectomy was unavoidable because of size and symptomatic infarction. The dominant histologic feature in the first was striking proliferation of sinus lining cells engorged with the IgA paraprotein. In the second there was dramatic expansion of the red pulp. In neither, despite using appropriate immunohistochemical techniques, could the enlargement of the spleen be attributed to infiltration by plasma cells that in the peripheral and blood and marrow had a distinctively unusual morphology. In these two individuals the pathophysiology remains obscure. In the first, although considered, it was not possible to meet the criteria for this being an example of littoral cell angioma. In the second, a postulated disseminated plasmacytoma with primary splenic sequestration remains unproven. This unique finding is, therefore, presented as descriptive pathology without recognisable explanation. PMID- 27414082 TI - Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma. AB - To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10 years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID- 27414083 TI - Signal Transduction by the Philadelphia Chromosome-encoded BCR/ABL Oncoproteins: Therapeutic Implications for Chronic Myeloid Leukemia and Philadelphia-positive Acute Lymphoblastic Leukemia. AB - The Philadelphia chromosomes characteristic of chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (ALL) encode chimeric protein tyrosine kinases (PTKs) derived by fusion of the normal BCR and ABL genes. The oncogenic properties of these BCR/ABL oncoproteins are dependent on their elevated PTK activity and on their ability to interact with multiple signal transduction systems. Here we summarize some of the key pathways which are activated by normal receptors with PTK activity and which modulate cell proliferation and survival. Next, we review some of the biochemical pathways initiated by BCR/ABL oncoproteins and discuss their possible relevance to the leukemic phenotype. We finally review experimental approaches designed to suppress signalling by BCR/ABL oncoproteins and discuss their potential therapeutic applications. PMID- 27414084 TI - Myeloid Leukemia After Cytotoxic Therapy and Other Hematotoxins. AB - Therapy-related leukemia is a neoplastic hematopoietic disorder arising in most cases from a multipotent stem cell and in a few cases from a lineage-committed progenitor. Therapy-related acute myeloid leukemia (t-AML) describes a clinical syndrome that exhibits important differences from AML that arises de novo [1]. The terms "therapy-related" or "treatment-related" leukemia are descriptive and are based on a patient's history of exposure to cytotoxic agents. They imply a causal relationship, but the mechanism of this transformation remains to be established. These terms may ultimately be too restrictive, since the leukemia that develops after exposure to benzene or atomic bomb irradiation is very similar or identical to the therapy-related leukemia syndrome. In the future, as various subtypes of leukemia are distinguished by specific genetic alterations, the terms "de novo" (or primary) and "therapy- related" leukemia will likely be discarded and specific etiologies will be incorporated into the diagnostic nomenclature. PMID- 27414085 TI - Adhesion of Hematopoietic Precursors to Human Stroma: Studies Using Normal Marrow Stromal Myofibroblasts and a Stromal Cell Line Transformed by SV40. AB - Adhesion of hematopoietic precursors to the marrow microenvironment appears to be a prerequisite for proliferation and differentiation of hematopoietic cells. In this report, we have studied the adhesion of CFU-GM from marrow CD34+ precursors to human marrow myofibroblasts and to an human stromal cell line, L2Ori-, transformed by a vector comprising the whole of the SV40 viral sequence except for the origin of replication. This Stro-l(+) cell line presents characteristics similar to those of vascular smooth muscle cells, since (i) few cells were alpha SM actin(+)while all cells were vimentin(+) but desmine(-) and a metavinculin band was consistently detected, (ii) all cells contained lysosomes filled with glycoproteins recognized by the monoclonal antibody 1B10, (iii) we detected EDa(+) EDb(-) pericellular fibronectin and intracellular beta1 and beta laminins and (iv) the cytokine expression pattern was similar to that of cells from colony derived cell lines. Transformation was confirmed by abnormal and irregular growth (hallmarked by crises with rather slow growth between crises), and the presence of some very large cells with several nuclei. Although presenting an usual stromal phenotype, this cell line could not sustain hematopoiesis from marrow CD34+ cells in coculture due to a complete inability of adhesion of CD34+ cells (0% of adherent CFU-GM vs. 20% on normal stromal myofibroblasts). The lack of adhesion was explained by abnormal expression of adhesion molecules and molecules involved in the organization of extracellular matrix: (1) at the membrane level: the lack of VCAM-1 and significant differences in the distribution of CD44 and integrins alpha1, alpha3, alpha4 and beta as compared to normal stroma; (2) at the level of focal adhesions: the predominance of the 200 kD fragment of talin (as opposed to that of 230 kD in normal stroma), and a significantly decreased expression of vinculin and alpha-actinin; (3) at the level of microfilaments: the decrease in polymerized actin and a large decrease of alpha-SM actin synthesis; and (4) at the level of extracellular matrix: very few fibronectin fibres. These data show that transformation can strongly and negatively affect the function of hematopoiesis maintenance by disrupting intercellular and extracellular matrix adhesion mechanisms of hematopoietic cells to the stroma, in particular by affecting the fibronexus. Our data suggest the need for extreme caution when using SV40 transformed cell lines and instead, make the case for the use of other means of immortalization (such as thermosensitive T, other transforming sequences, introduction of inducible promoters). PMID- 27414087 TI - Gold Tris(carboxyphenyl)corroles as Multifunctional Materials: Room Temperature Near-IR Phosphorescence and Applications to Photodynamic Therapy and Dye Sensitized Solar Cells. AB - Two amphiphilic corroles-5,10,15-tris(3-carboxyphenyl)corrole (H3[mTCPC]) and 5,10,15-tris(4-carboxyphenyl)corrole (H3[pTCPC])-and their gold complexes have been synthesized, and their photophysical properties and photovoltaic behavior have been investigated. Like other nonpolar gold corroles, Au[mTCPC] and Au[pTCPC] were both found to exhibit room temperature phosphorescence in deoxygenated solutions with quantum yields of ~0.3% and triplet lifetimes of ~75 MUs. Both compounds exhibited significant activity as dyes in photodynamic therapy experiments and in dye-sensitized solar cells. Upon irradiation at 435 nm, both Au corroles exhibited significant phototoxicity against AY27 rat bladder cancer cells while the free-base corroles proved inactive. Dye-sensitized solar cells constructed using the free bases H3[mTCPC] and H3[pTCPC] exhibited low efficiencies (?1%), well under that obtained with 5,10,15,20-tetrakis(4 carboxyphenyl)porphyrin, H2[pTCPP] (1.9%, cf. N719 9.5%). Likewise, Au[pTCPC] proved inefficient, with an efficiency of ~0.2%. By contrast, Au[mTCPC] proved remarkably effective, exhibiting an open-circuit voltage (Voc) of 0.56 V, a short circuit current of 8.7 mA cm(-2), a fill factor of 0.72, and an efficiency of 3.5%. PMID- 27414088 TI - Kinetics of Antimicrobial Activity of Amoxicillin/Clavulanic Acid and Metronidazole against beta-Lactamase-Producing Bacteroides fragilis Group. AB - Bacteroides fragilis group are the most common anaerobic bacteria isolated in clinical specimens. The use of a beta-lactam with a beta-lactamase inhibitor should result in a marked increase in the group's sensitivity to the beta lactams. Since the activity (MIC) shown by the amoxicillin + clavulanic acid combination against Bacteroides fragilis group is good, other parameters of in vitro activity have been studied. This study was also done with metronidazole. The minimum inhibitory concentration (MIC) was determined in 26 strains of Bacteroides fragilis group (14 B. fragilis; 5 B. thetaiotaomicron; 4 B. vulgatus; 3 B. distasonis). Likewise, the minimum bactericidal concentration (MBC), the killing curve, the sub-MIC and post-antibiotic effect were determined. The MIC ranged between 0.5 and 32 mg/l. The MBC was two- to four-fold the MIC for amoxicillin/clavulanic acid, and one- to two-fold the MIC for metronidazole for most strains. The killing curve showed a continuous decrease, sloping most sharply between 0-2 hours and 6-8 hours. Amoxicillin + clavulanic acid showed a post-antibiotic effect between 2 and 4 hours. The inhibitory minimum antibiotic concentration was one-half the MIC for most strains. PMID- 27414086 TI - NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway. AB - N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however beta-catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and beta-catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and beta-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression. PMID- 27414089 TI - Keeping cells in their place: the future of stem cell encapsulation. PMID- 27414090 TI - Challenges in Designing Psychological Treatment Studies for Sexual Dysfunction. PMID- 27414091 TI - Outcome Following Surgical Interventions for Micrognathia in Infants With Pierre Robin Sequence: A Systematic Review of the Literature. AB - BACKGROUND: Tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), and subperiosteal release of the floor of the mouth (SPRFM) are the most commonly performed surgical procedures to treat severe airway obstruction in infants born with Pierre Robin sequence (PRS). OBJECTIVES: To determine the rate of failure of each type of procedure, in terms of mortality and the need for tracheostomy, and to determine what proportion of infants have significant airway obstruction postoperatively as determined by polysomnography (PSG) and compare the data by procedure type. METHOD: A comprehensive literature search (1981 through June 2015) was done of the National Library of Medicine database using PubMed. Extracted data included diagnosis, type of surgery, and outcome including mortality, need for postoperative tracheostomy and details of PSG. Persistence of significant airway obstruction was defined as an apnea-hypopnea index >15 events/h on PSG. RESULTS: Both mortality rate and need for tracheostomy were low for all procedures. Many studies lacked sufficient detail to identify significant airway obstruction postoperatively. In studies with sufficient data, MDO was associated with the lowest percentage of significant airway obstruction postprocedure (3.6%) compared to 50% for infants who underwent TLA. Insufficient PSG data was available for patients who were treated with SPRFM. CONCLUSIONS: There is a paucity of objective PSG data to definitively assess postoperative airway outcomes for PRS. MDO appears to be the most effective technique based on the available PSG data. Standardized use of PSG may lead to better identification and treatment of patients at risk for suboptimal airway outcomes postoperatively. PMID- 27414092 TI - Editor's Mail. PMID- 27414093 TI - Problems solutions. PMID- 27414094 TI - What's happening in medicine. PMID- 27414095 TI - Washington background. PMID- 27414096 TI - Heart disease in adolescence. PMID- 27414097 TI - Clinical Outlines. PMID- 27414098 TI - Heart Disease in Adolescence. PMID- 27414099 TI - Ready Source on Heart Disease in Adolescence. PMID- 27414101 TI - Therapeutic Index to Advertisers. PMID- 27414102 TI - Real-Time Optical Biopsy of Lung Cancer. PMID- 27414103 TI - Relationship between microvessel density and cancer stem cells in tumor angiogenesis: a meta-analysis. AB - AIM: Several studies have shown that cancer stem cells (CSCs) promote tumor angiogenesis and are involved in tumor growth. A meta-analysis was conducted to evaluate the association between cancer stem cell markers expression and microvessel density (MVD). METHODS: Relevant literature was identified from diverse databases. The Stata 12.0 and Review Manager 5.3 software were used to performed meta-analysis. RESULTS: Sixteen studies investigating the correlation between CSCs and tumor angiogenesis were included in a total of 1409 cases. The result showed that positive CSC markers expression were associated with increased MVD count in human tumors and CSC-transplanted mouse tumor models (p < 0.0001). CONCLUSION: CSCs may be associated with angiogenesis during the growth and development of tumors. PMID- 27414104 TI - Indoor pollutant hexabromocyclododecane enhances house dust mite-induced activation of human monocyte-derived dendritic cells. AB - The indoor pollutant hexabromocyclododecane (HBCD) has been added as flame retardant to many consumer products but detaches and accumulates in house dust. Inhalation of house dust leads to exposure to house dust mite (HDM) allergens in the presence of HBCD. Activation of dendritic cells is crucial in the sensitization to HDM allergens. The current study examined whether exposure to HBCD affected activation/maturation of HDM-exposed human dendritic cells (DC). Human monocyte-derived DC (moDC) were exposed simultaneously to HDM and a concentration range of HBCD (0.1-20 MUM) in vitro. HDM exposure of moDC induced expression of co-stimulatory molecule CD80 and production of pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha. However, simultaneous exposure of moDC to HBCD and HDM enhanced the expression of antigen presenting molecule HLA-DR, co-stimulatory molecule CD86 and pro inflammatory cytokine IL-8 depending on the dose of HBCD. Our results indicate that simultaneous exposure of HDM and HBCD can enhance the antigen presentation and maturation/activation of DC. PMID- 27414106 TI - Scanning sports. PMID- 27414105 TI - Effectiveness and safety of tocilizumab in achieving clinical and functional remission, and sustaining efficacy in biologics-naive patients with rheumatoid arthritis: The FIRST Bio study. AB - OBJECTIVE: To evaluate effectiveness and safety of tocilizumab (TCZ) in biologic naive Japanese patients with rheumatoid arthritis (RA) in real-world settings, and to analyze the relationship between disease duration and clinical outcomes. METHODS: The FIRST Bio study was a postmarketing surveillance study of intravenous TCZ in biologics-naive patients who had a prior inadequate response or were intolerant to >=1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Effectiveness, safety, and concomitant csDMARD administration were assessed. RESULTS: Of the 839 patients analyzed, 72.3% completed 52 weeks of treatment. The Clinical Disease Activity Index (CDAI) remission rate at week 52 was 36.8%. Contributing factors for CDAI remission were younger age, early disease stage, and no comorbidities. Health Assessment Questionnaire Disability Index <=0.5 was achieved in 65.1% of patients, and was significantly associated with disease duration. Discontinuation of concomitant methotrexate (MTX) and glucocorticoids (GCs) was possible in 19.3% and 34.1% of patients, respectively, without decreasing remission rate. The incidence (events/100 patient-years) of serious adverse events was 18.09, the most common being infection. CONCLUSION: These data validate the importance of TCZ treatment in the early stages of RA in biologic-naive patients to achieve increased effectiveness. The safety profile of TCZ was reconfirmed. Furthermore, TCZ therapy may allow discontinuation of concomitant MTX and GCs without affecting remission. PMID- 27414108 TI - Forum. PMID- 27414109 TI - Running wild. PMID- 27414111 TI - Wrap-up. PMID- 27414112 TI - Coming in sportsmedicine. PMID- 27414113 TI - Controversies in Pediatric Sports Medicine. AB - In brief: Primary care physicians often need to advise pediatric patients and their parents on medical issues in children's sports, but for many areas of sports medicine, data are inconclusive, recent, or nonexistent. For instance, infant exercise programs seem to be increasing in popularity with parents, but the passive exercises have little or no effect on an infant's development. And on another front, some schools still do not allow high school girls to try out for sports like football and wrestling, yet this position has been challenged in court by a few girls. This article highlights these and other controversial issues that have arisen in children's sports, 'he author discusses these issues in light of Policy statements from the American Academy of Pediatrics. PMID- 27414114 TI - Acute Knee Injury in a Rock Musician. AB - A group of experts met to discuss a case from the North Sydney Orthopaedic and Sports Medicine Centre. This case conference is part of a series featuring a variety of sports medicine topics. PMID- 27414115 TI - Endurance Training in Middle-Aged Male Physicians. AB - In brief: Vigorous exercise has been associated with reduced cardiovascular risk factors and a lower incidence of coronary heart disease. To determine the effects of endurance training on middle-aged men, a group that is at risk for heart disease, two groups of Physicians were surveyed: 1,269 runners (members of the American Medical Joggers Association who had been running at least 10 miles per week) and 683 nonrunners (members of the AMA). These groups were chosen because they are similar in age, sex, life-style, profession, socioeconomic position, and knowledge about health. Results showed that the runners had lower body weight and reduced cardiovascular risk factors, and that they smoked fewer cigarettes. However, prospective studies are needed to determine both the risks and benefits of endurance exercise. PMID- 27414117 TI - Overuse Syndromes of the Lower Extremity. AB - In brief: Overuse injuries of the lower extremity represent a frequent, significant problem. This article discusses management of the most common overuse disorders: anterior tibialis strain, medial tibial stress syndrome, compartment syndrome, stress fractures, and Achilles tendinitis. These injuries often are the culmination of a process (repetitive stress) rather than the result of a single event. Grading injuries on a scale of 1 to 4 according to severity can help determine the correct treatment. The primary treatment goal is to reduce inflammation through icing, rest, and appropriate use of nonsteroidal anti inflammatory agents. For a safe return to pain-free activity, additional measures are required to correct biomechanical problems, educate the athlete on training techniques, and begin a gradual reconditioning program. PMID- 27414116 TI - Athletic Heart Syndrome. AB - In brief: Regular exercise training results in a variety of cardiovascular adaptations including increases in left ventricular chamber size and wall thickness, and in resting vagal tone. These anatomic and physiologic changes may produce abnormalities in the ECG and echocardiogram. In the past, physicians often interpreted these changes as pathologic and advised cessation of training. But modern research has demonstrated that the cardiovascular changes are physiologic and are associated with preserved or enhanced cardiovascular function. It is important, however, to distinguish this physiologic hypertrophy from the pathologic hypertrophy of such conditions as obstructive cardiomyopathy. PMID- 27414119 TI - Asthma Not a Hurdle for Joyner-Kersee. PMID- 27414118 TI - Wheezing or Breezing Through Exercise-Induced Asthma. AB - Treatment of athletes with exercise-induced asthma (EIA) varies depending on the severity of the condition and other factors. In this article, several physicians discuss the tests they use to diagnose EIA, the medications they typically prescribe and why, as well as the importance of properly educating athletes about EIA. PMID- 27414120 TI - Are the Risks of Sport Scuba Diving Being Underestimated? AB - A lawsuit has challenged the safety of the tables widely used in scuba diving. Other concerns also have emerged: A condition known as patent foramen ovale may increase the risk of decompression sickness, and studies are raising questions about the long-term effects of diving. PMID- 27414121 TI - Spinal Cord Injuries: The High Cost of Careless Diving. AB - Programs that teach safe diving practices can go a long way toward eliminating diving accidents-the fourth leading cause of spinal cord injuries. New prevention programs, rescue techniques, and treatment methods are helping to reduce the number and severity of these injuries. PMID- 27414122 TI - Exercise adviser. PMID- 27414124 TI - Beyond the direct costs of hepatitis C treatment: the balance between costs and ethics. PMID- 27414125 TI - Role of Stereotactic Body Radiation Therapy with Volumetric-Modulated Arcs and High-Intensity Photon Beams for the Treatment of Abdomino-Pelvic Lymph-Node Metastases. AB - AIM: To study clinical outcome for oligometastatic patients (abdominal lymph-node metastases) treated with stereotactic body radiation therapy. MATERIALS AND METHODS: Seventy-one patients were studied retrospectively. Dose prescription was 45 Gy in six fractions. Clinical outcome was assessed with actuarial analysis. RESULTS: The median follow-up was 1.5 years; 45 patients (63.3%) had solitary metastasis, and 26 (36.6%) had multiple lesions. Local control was achieved in 97.5% with a 1-year actuarial rate of 83%. Two-year progression-free survival was 63.1%, and the overall survival was 76.9%. Two patients (3%) developed grade 2 gastro-enteric toxicity. CONCLUSIONS: The treatment provided adequate clinical response in the management of oligometastatic cases. PMID- 27414127 TI - A Raney Cobalt Mediated Reductive Cyclization Route to the Uleine Alkaloid Gilbertine. AB - Reductive cyclization of the 2,4,5-trisubstituted cyclohexenone 16 using dihydogen in the presence of Raney cobalt afforded compound 17 (60%) that could be elaborated over a further five steps, including one involving a cationic cyclization process, into the racemic modification of the unusual uleine alkaloid gilbertine. Single-crystal X-ray analyses of compounds (+/-)-1, 16, and a derivative of 17 are reported. PMID- 27414126 TI - CHOROIDAL ALTERATIONS IN ABCA4-RELATED RETINOPATHY. AB - PURPOSE: To investigate choroidal alterations in ABCA4-related retinopathy. METHODS: Mean choroidal thickness and subfoveal choroidal thickness were measured in the right eyes of 40 patients with ABCA4-related retinopathy using enhanced depth imaging optical coherence tomography. The right eyes of 65 age-matched healthy subjects were used for comparison. RESULTS: Compared with controls, patients with ABCA4-related retinopathy revealed a reduced subfoveal choroidal thickness ([mean +/- SEM] 347 +/- 10 MUm vs. 302 +/- 12 MUm; P = 0.006) and mean choroidal thickness (315 +/- 9 MUm vs. 275 +/- 10 MUm; P = 0.005). This difference was mainly due to choroidal thinning in eyes with reduced photopic and/or scotopic amplitudes on full-field electroretinography. Atrophy of the retinal pigment epithelium (RPE) was associated with a thinner choroid compared with eyes without RPE atrophy (subfoveal choroidal thickness: 277 +/- 17 MUm vs. 341 +/- 16 MUm; mean choroidal thickness: 252 +/- 13 MUm vs. 313 +/- 13 MUm; both, P <= 0.001), but choroidal thinning was not restricted to the area of RPE atrophy. Choroidal thickness was similar to controls when RPE atrophy and functional loss were limited to the central retina. There was no association between visual acuity and choroidal thickness. CONCLUSION: The results indicate choroidal alterations in widespread ABCA4-related retinopathy, especially when associated with atrophy of the RPE. The absence of focal choroidal thinning in areas of RPE atrophy is suggestive for a diffusible factor from the RPE sustaining the choroidal structure. PMID- 27414128 TI - Role of Long-Chain Polyunsaturated Fatty Acids in Early Human Neurodevelopment. AB - While breast-fed infants receive considerable amounts of preformed dietary arachidonic and docosahexaenoic acids in human milk, most of the currently available infant formulae are devoid of long-chain polyunsaturated fatty acids. Observational data obtained in preterm as well as in full-term infants indicate that breast feeding as compared to feeding formula is associated with better results in various tests on visual and cognitive development. In several randomised, placebo controlled, double-blind studies carried out in preterm infants, feeding formula with as compared to without long-chain polyunsaturated fatty acids resulted in improved maturation of visual functions. However, beneficial effects of providing dietary long-chain polyunsaturated fatty acids were seen only in some but not in all randomised studies on the development of visual functions in full-term infants. Data obtained in two recent randomised clinical trials on cognitive functions in full-term infants indicate that supplementation of formula with arachidonic and docosahexaenoic acids offers some neurodevelopmental benefits detectable at the ages of 4 and 10 months. Confirmation of shortterm results in longer follow-up studies appears desirable, but available evidence support the supplementation of both preterm and term infant formulae with arachidonic and docosahexaenoic acids in amounts and ratios characteristic to those found in mature human milk. PMID- 27414129 TI - Towards an Understanding of Physiological Body Mass Regulation: Seasonal Animal Models. AB - This review is based around a number of interlinked hypotheses that can be summarised as follows: (i) mammalian body mass is regulated, (ii) the mechanisms that effect this regulation are common to all mammalian species, including humans, (iii) the neurochemical substrates involved in long term body mass regulation and in determining the level of body mass that will be defended may not be the same as those involved in short term energy homeostasis, or body mass defence, or may be differentially engaged, and (iv) "appropriate" body mass is encoded somewhere within the mammalian brain and acts as a comparator to influence both nutritional and reproductive physiology. These issues are of direct relevance to the epidemic of obesity in the Westernised human population and the poor success rate of conventional weight loss strategies. It is our contention that seasonal rodent models, and the Siberian hamster in particular, represent extremely valuable tools for the study of the mechanistic basis of body mass regulation. The Siberian hamster model is often perceived as an unusual mammalian variant that has evolved an almost counter-intuitive strategy for surviving periods of anticipated seasonal food shortage. However, there is compelling evidence that these animals are able to adjust their body mass continually and progressively according to their photoperiodic history, i.e. a seasonally-appropriate body mass. These adjustments to appropriate body mass are memorised even after the animals have been driven away from their normal body mass trajectory by imposed food restriction. Thus, photoperiod, acting through the pineal hormone, melatonin, is able to reset the desired body mass for a given time in the seasonal cycle. Importantly, daylength provides a tool to manipulate the body mass control system in an entirely physiological and stress-free manner. While resetting of body mass by photoperiod represents a level of control apparently confined to seasonal mammals, it has the potential to reveal mechanisms of generic importance in the regulation of energy homeostasis. PMID- 27414130 TI - Response to Energy Dilution in the Short Term: Evidence of Nutritional Wisdom in Young Children? AB - Young children respond to energy dilution achieved using fat or sugar substitutes by compensating for reduced energy within a single meal. The ability to respond to energy dilution in the short term may diminish with age, since adults do not reliably demonstrate accurate caloric compensation in the short term. Two experiments were conducted to examine caloric compensation across age groups. In Experiment 1,15 young children (2-5 years) and 10 older children (7-10 years) received regular (100 g: 73 kcal) and low-calorie (100 g: 6 kcal) raspberry gelatin dessert as a mid-morning snack on two test days separated by at least 2 weeks. Young children demonstrated caloric compensation by consuming more following the low-calorie snack (571.3 +/- 48.8 kcal) than after the regular snack (487.7 +/- 31.5 kcal). Older children failed to adjust intake in response to the difference in energy. In Experiment 2, a similar procedure was used but young children (n = 19) received 150 g of raspberry gelatin dessert (9 kcal vs. 109 kcal) and older children (n = 12) received 225 g of gelatin dessert (13 kcal vs. 164 kcal). The compensation index (COMPX) indicated that young children (88.1 +/- 22.4%) compensated better than older children (21.5 +/- 21.9%). Short-term caloric compensation may diminish with age, possibly reflecting a transition from using unlearned internal cues to a more adult pattern of eating influenced by external cues and learning. PMID- 27414131 TI - Ethanol Consumption by Lactating Rats Induces Changes in Pup's Fatty Acid Profiles. AB - From parturition, lactating Wistar rats were given 20% ethanol in drinking water and solid diet ad libitum (ET group) or were pair-fed to the ET group (PF group) or were given water and solid diet ad libitum (control group, C). Animals were studied on day 12 of lactation and/or treatment, when dams were separated from their litters and 2-4 hours latter they were i.p. injected with oxytocin for milk collection under anaesthesia. Maternal food intake, weight gain and pup's body weight were lower in ET than in C rats. When compared to C rats, milk of ET dams had a decreased proportion of C14:0 and C22:6 n-3 fatty acids while an increase in C18:0,C16:1 and C18:1 n-9 was detected, whereas when compared to PF it had higher C8:0,C10:0,C18:0,C18:1 n-9, C18:2 n-6 and lower C20:5 n-3 and C22:6 n-3. Body weight was lower in pups from ET than in those from C or PF, and whereas brain weight and brain lipid content was lower in ET and PF pupsthan in C, total phospholipid (PL) brain content was similar among the groups. The ratio of C20:3 n-9 to C20:4 n-6 in brain PL was higher in ET pups than in either C or PF, indicating an essential fatty acid deficiency in the formers. Ethanol treatment also decreased the proportional amount of C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 in brain PL as compared to C, whereas from these fatty acids only C18:3 n-3, C20:5 n-3 and C22:6 n-3 were decreased in PF. On the other hand, the proportion of C22:6 n-3 was significantly lower in the pups of ET group than in PF animals. Present results show that maternal intake of ethanol during lactation in the rat modifies milk lipid composition and that these effects are not caused by the undernutrition condition of the animals. These effects alter fatty acid composition of brain PL in pups, and such effect may contribute to its abnormal development. PMID- 27414132 TI - Stress, Breakfast Cereal Consumption and Susceptibility to Upper Respiratory Tract Illnesses. AB - Two diary studies were conducted to examine the effects of stress and consumption of breakfast on the incidence and severity of upper respiratory tract illnesses. Both studies showed that negative life events were associated with the occurrence of URTIs. Breakfast consumption and consumption of breakfast cereal were also associated with illness incidence and severity. The effects of stress and breakfast consumption were found to be independent. Further research is now required to elucidate the mechanisms underlying the beneficial effects of breakfast cereal consumption on the occurrence of upper respiratory tract illnesses. PMID- 27414133 TI - Dose-Dependent Effect of alpha-Lactalbumin in Combination with Two Different Doses of Glucose on the Plasma Trp/LNAA Ratio. AB - A deficient brain serotonin function has been demonstrated in psychiatric disorders and increases in brain serotonin ameliorate emotional and behavioural abnormalities found in depression. The uptake of the serotonin precursor tryptophan into the brain is dependent on nutrients that influence the cerebral availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp/LNAA). In the present study, we investigated the time- and dose dependent effects of alpha-lactalbumin enriched whey protein with a high tryptophan content in combination with two doses of glucose on plasma Trp/LNAA. Twelve healthy subjects participated in a double blind cross-over study and ingested 200 ml orange juice added with glucose alone or mixed with either 5,10, and 20 g alpha-lactalbumin or 20 g alpha-lactalbumin hydrolysate. One half of the subjects received the orange juice with 25 g glucose, whereas the other half of the subjects received the juice with 50 g glucose. Results revealed a relationship between alpha-lactalbumin dosage and increases in plasma Trp/LNAA [P< 0.001]. Different doses interacted with time dependent changes in plasma Trp/LNAA [P < 0.0001] such that the most prolonged increase was found with 20 g alpha-lactalbumin [P < 0.0001]. Changes in plasma Trp/LNAA were not affected by glucose dose. Since increases in plasma Trp/LNAA are indicative of increased serotonin concentrations in the brain, this study shows that ingestion of 20 g alpha-lactalbumin may be a suitable dietary method to investigate the effect of alterations in brain serotonin. PMID- 27414134 TI - The Involvement of Enkephalin System in Analgesia Induced by Brain Iron Deficiency. AB - Iron deficiency (ID) induces in rats marked reduction of brain iron and dopamine D2 receptor. The resultant effects are a wide variety of changes in dopamine mediated behaviors including thermo-regulation, motor activity, stereotyped behavior and diminished learning. Another behavioral change resulting from ID rats is an increase in the pain threshold, which is dependent on the duration and severity of ID. The results showed that peripheral administration of enkaphalines (0.1-3.0 mg/kg I.P.) potentiates ID-induced analgesia and causes a higher pain threshold, a phenomenon not observed in control rats.This effect may be associated with the known functional alteration in blood brain barrier resulting from ID. The opiate antagonists, naloxone (2 mg/kg and MIF-I (1 mg/kg), blocked the opiate-induced pain threshold potentiation in ID. Furthermore, the levels of dynorphin B and met-enkephalin are significantly increased in dopamine opiate rich brain areas (caudate nucleus, substantia nigra, nucleus accumbens and globus pallidus) during ID. These phenomena can be reversed by placing rats on iron plus (control) diet for 24 days. It is concluded that a decrease in brain dopamine neurotransmission is associated with an increased functional level of the opiate system and that this mechanism mediates not only the analgesic effect but may also be associated with learning deficit observed in ID rats. PMID- 27414135 TI - Preferable Monosodium Glutamate and Sodium Chloride Solutions do not Affect Diurnal Norepinephrine Release in the Rat Lateral Hypothalamus. AB - Rats prefer hypo-osmolar solutions of monosodium glutamate (MSG) to water. The unique taste of MSG, called umami, has been suggested to be involved in protein homeostasis. We have investigated diurnal intake patterns of hypo-osmolar MSG solution (0.06 M) in rats fed a protein sufficient diet. Compared to water intake, animals showed a significant preference for MSG solution during the first part of dark phase (dark phase, 19:00-7:00; first part, 19:00-2:00). In contrast, no preference was found during the final part of dark phase or during light phase. No changes in food intake between the two tested groups were found. Although rats were offered MSG solution for five consecutive days, no day-to-day variations in intake were evident, suggesting that MSG preference is unlearned. Activation of the lateral hypothalamus (LH) was previously detected during of MSG solution intake in rats. Using a microdialysis technique, we evaluated LH norepinephrine (NE) release in rats drinking water, salt solution (0.06 M) and MSG solution (0.06 M). Diurnal variations of LH NE release were found in all animals without significant differences between the three groups. These data do not support involvement of LH NE in the brain recognition circuit for preferable umami or NaCl solutions. PMID- 27414136 TI - You Are a Member of the Premiere Trauma Nursing Organization. PMID- 27414137 TI - Summer Trauma. PMID- 27414138 TI - STN Demonstrates Commitment to Clinical Components of Trauma Nursing Through Establishment of Clinical Director at Large Board Position and Clinical Excellence Award. PMID- 27414139 TI - The Legal Limit: Differences in Injury Severity Score for Vehicular Crashes. AB - In 2013, the National Transportation Safety Board advised lawmakers in the United States to reduce the legal limit of blood alcohol content (BAC) from 0.08% to 0.05%. The purpose of this research was to evaluate the rationale for reducing the legal limit of BAC to 0.05% through analysis of the relationship between BAC and injury severity. A correlational study was conducted on patients with positive BAC involved in a motor vehicular collision. Retrospective review of 446 trauma patients (aged 18-80 years) injured in a vehicular collision routinely screened for BAC was conducted. Two groups were compared: Group 1, patients with nonzero blood alcohol concentration (n = 101); and Group 2, patients with zero blood alcohol (n = 345). Standard statistical analyses were utilized. A total of 101 patients (23%) had a detectable BAC on admission. Patients with a detectable BAC were younger (33 and 44 years) and more likely to be male (27% and 16%). There was no statistically significant association between both injury severity score (ISS) and BAC or between ISS and age. There was no significant correlation between higher BAC and a higher ISS. Positive BAC alone may not affect ISS, but the potential for risk-taking behaviors by drivers under the influence may increase injury severity. PMID- 27414140 TI - Delta Alerts: Changing Outcomes in Geriatric Trauma. AB - Geriatric trauma patients (GTPs) suffering minor injuries have suboptimal outcomes compared with younger populations. Patients 65 years or older account for 10% of all traumas but 28% of all trauma deaths. This trauma center established a third tier trauma alert specifically targeting GTPs at risk for poor outcomes. A Delta Alert is activated when GTPs suffer injuries that fall outside traditional trauma alert guidelines. Early identification and treatment of injuries and expedited referral to specialty groups have improved our GTPs' outcomes including decreased mortality and length of stay and increased percentage of GTPs who are discharged home. PMID- 27414141 TI - A Qualitative Analysis of Children's Emotional Reactions During Hospitalization Following Injury. AB - Children who sustain injuries are at risk for experiencing traumatic stress reactions. Few studies have obtained detailed, qualitative information regarding children's and parents' own understanding of their experiences during the peritrauma period. Understanding children's injury and early hospital experiences is crucial to inform the development of early interventions during the peritrauma period, which speak to these concerns. The primary purpose of this study was to understand child and parent views of the stressors experienced by children hospitalized for an injury. A secondary aim was to identify children's feelings and thoughts about injury- and hospital-related stressors. Ten children and their parents participated in semistructured interviews. Interviews were audio recorded, transcribed, and coded. Stressors were classified into 5 domains: procedural concerns, uncertainty, sleep and nutrition challenges, being confined to the hospital, and home preparation. Children and parents were more likely to articulate feelings about stressors than thoughts about stressors. Feelings reported by children and parents were predominantly negative. Children and parents may have an easier time expressing feelings than thoughts, which has implications for communicating with medical teams as well as for psychological treatment. Future research should examine how children's perceptions of their injury- and hospital-related experiences relate to later outcomes such as traumatic stress reactions. PMID- 27414142 TI - Application and Evaluation of Knowledge Retention Related to Advanced Trauma Care for Nurses (ATCN) Course Content: A Preliminary Study. AB - The Advanced Trauma Care for Nurses (ATCN) course was designed to help nurses increase their knowledge in management of the multiple trauma patient. To determine whether the trauma-related knowledge of ATCN course takers differed from nontakers, assess the factors associated with ATCN content knowledge among course takers, and explore the extent to which the ATCN content was used by course takers in their clinical practice. A cross-sectional online survey of 78 ATCN takers (nurses who had successfully completed the ATCN course within the previous 3 years) and 58 ATCN nontakers (a control group of nurses who had not taken the course but who worked in comparable clinical settings) was conducted. The survey consisted of demographic questions and a 15-item knowledge test spanning the ATCN course content. ATCN takers were also asked about the frequency with which a specific ATCN content had been used in their practice since taking the course. ATCN takers had a significantly higher (mean +/- SD = 10.6 +/- 2.2) total score on the study test than the ATCN nontakers (mean +/- SD = 6.4 +/- 2.6); t(134) = -10.0, p < .001. A shorter time since course completion was associated with higher knowledge scores. ATCN takers rated the clinical relevance and applicability of the course content as high. The findings suggest that completing the ATCN course increases knowledge levels of trauma patient management and that the ATCN course content is clinically relevant to the nurses. However, higher knowledge scores were observed for the most recent study participants, suggesting that booster sessions for ATCN course participants may be warranted. PMID- 27414143 TI - Trauma Tactics: Rethinking Trauma Education for Professional Nurses. AB - According to the National Trauma Institute (2015), trauma accounts for more than 180,000 deaths each year in the United States. Nurses play a significant role in the care of trauma patients and therefore need appropriate education and training (L. ). Although several courses exist for trauma education, many nurses have not received adequate education in trauma management (B. ; L. ). Trauma Tactics, a 2 day course that focuses on high-fidelity human patient simulation, was created to meet this educational need. This descriptive study was conducted retrospectively to assess the effectiveness of the Trauma Tactics course. Pre- and postsurveys, tests, and simulation performance were used to evaluate professional nurses who participated in Trauma Tactics over a 10-month period. Fifty-five nurses were included in the study. Pre- and postsurveys revealed an increase in overall confidence, test scores increased by an average of 2.5 points, and simulation performance scores increased by an average of 16 points. Trauma Tactics is a high quality course that provides a valuable and impactful educational experience for nurses. Further research is needed to evaluate the long-term effects of Trauma Tactics and its impacts on quality of care and patient outcomes. PMID- 27414144 TI - The Relationship Between Traumatic Injury in Children and Long-Term Use of Health and Social Services by Children and Their Families. AB - To increase understanding of relationships between general traumatic injury in children and long-term use of resources in the health care and social services (HSS) sectors by these children and their families 8-10 years after traumatic injury. This study was a cross-sectional retrospective cohort study of prognosis from 2001 to 2003 that quantified recent expenditures on and use of HSS by children and also by their parents. Forty-eight cases of children were selected from the Hamilton Health Sciences pediatric trauma database in the period from January 2001 to December 2003 after incurring a traumatic injury with Injury Severity Score greater than 12. The average total cost to the HSS system per child's family was $4,326.62 during the preceding 6 months. During the same period, average use of HSS was 7 visits. Total service costs incurred by caregivers of injured children increased with severity of the traumatic injury (p= .009). Caregiver HSS use was higher when the injury was caused by a motor vehicle accident than by other types of accidents (p< .001) and increased with the injury severity (p< .001). HSS use by children was related to gender (p< .001), injury mechanism (p< .001), age at accident (p< .001), and time since accident (p= .012), among other factors. Pediatric trauma appears to have long term effects on expenditures on and use of HSS by the affected children and their families. The findings emphasize the need for long-term assessment and possible delivery of services to the families of the injured children. PMID- 27414145 TI - Advanced Practice Nursing Committee on Process Improvement in Trauma: An Innovative Application of the Strong Model. AB - This article aims to summarize the successes and future implications for a nurse practitioner-driven committee on process improvement in trauma. The trauma nurse practitioner is uniquely positioned to recognize the need for clinical process improvement and enact change within the clinical setting. Application of the Strong Model of Advanced Practice proves to actively engage the trauma nurse practitioner in process improvement initiatives. Through enhancing nurse practitioner professional engagement, the committee aims to improve health care delivery to the traumatically injured patient. A retrospective review of the committee's first year reveals trauma nurse practitioner success in the domains of direct comprehensive care, support of systems, education, and leadership. The need for increased trauma nurse practitioner involvement has been identified for the domains of research and publication. PMID- 27414147 TI - A Key to Success: Building an Internal Trauma Education Program. AB - Developing an internal education program that specifically meets the needs of your trauma center's nurses is fundamentally an optimal method in educating. This article offers an overview of an internally developed trauma educational series that was created for novice and experienced nurses who work in a Level 1 trauma center. PMID- 27414146 TI - Epidemiological Characteristics and Overall Burden of Accidental Injuries in Navarra, Spain: Epidemiology of Injuries in Children. AB - Injuries caused by accidents or violent situations in pediatric patients are a serious social problem where prevention plays a key role. The aim of this study was to describe the epidemiological situation of pediatric injuries in Spain. A prospective study of pediatric patients receiving care in the Emergency Service of the Complejo Hospitalario de Navarra due to for reasons of accidental injury was conducted. The study covered a period of 1 year and assessed a total of 16 variables. There were a total of 8,876 patients, of whom 56.4% were males. Traumatic injuries such as fractures and craniocerebral trauma were identified as the most frequent injuries, occurring as a result of injuries mainly in the home. In females, there was a decrease in the incidence of injuries related to age. There was a greater incidence at the end of the day, during the weekend, and in the months of March to October. The epidemiological profile of pediatric patients who met with accidents in Navarra, Spain, is described. The knowledge of the main areas and factors related to injuries allows us to improve preventive measures, which would contribute to better control in this region of Spain. PMID- 27414148 TI - Trauma Tactics: Rethinking Trauma Education for Professional Nurses. PMID- 27414149 TI - Advanced Practice Nursing Committee on Process Improvement in Trauma: An Innovative Application of the Strong Model. PMID- 27414150 TI - The impact of underreporting and overreporting on the validity of the Personality Inventory for DSM-5 (PID-5): A simulation analog design investigation. AB - The Personality Inventory for DSM-5 (PID-5) is a 220-item self-report instrument that assesses the alternative model of personality psychopathology in Section III (Emerging Measures and Models) of DSM-5. Despite its relatively recent introduction, the PID-5 has generated an impressive accumulation of studies examining its psychometric properties, and the instrument is also already widely and frequently used in research studies. Although the PID-5 is psychometrically sound overall, reviews of this instrument express concern that this scale does not possess validity scales to detect invalidating levels of response bias, such as underreporting and overreporting. McGee Ng et al. (2016), using a "known groups" (partial) criterion design, demonstrated that both underreporting and overreporting grossly affect mean scores on PID-5 scales. In the current investigation, we replicate these findings using an analog simulation design. An important extension to this replication study was the finding that the construct validity of the PID-5 was also significantly compromised by response bias, with statistically significant attenuation noted in validity coefficients of the PID-5 domain scales with scales from other instruments measuring congruent constructs. This attenuation was found for underreporting and overreporting bias. We believe there is a need to develop validity scales to screen for data-distorting response bias in research contexts and in clinical assessments where response bias is likely or otherwise suspected. (PsycINFO Database Record PMID- 27414151 TI - Evaluating item endorsement rates for the MMPI-2-RF F-r and Fp-r scales across ethnic, gender, and diagnostic groups with a forensic inpatient sample. AB - The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) F(p) (Infrequency Psychopathology) scale was developed to measure overreporting in a manner that was minimally confounded by genuine psychopathology, which was a problem with using the MMPI-2 F (Infrequency) scale among patients with severe mental illness. Although revised versions of both of these scales are included on the MMPI-2 Restructured Form and used in a forensic context, no item-level research has been conducted on their sensitivity to genuine psychopathology among forensic psychiatric inpatients. Therefore, we examined the psychometric properties of the scales in a sample of 438 criminally committed forensic psychiatric inpatients who were adjudicated as not guilty by reason of insanity and had no known incentive to overreport. We found that 20 of the 21 Fp-r items (95.2%) demonstrated endorsement rates <= 20%, with 14 of the items (66.7%) endorsed by less than 10% of the sample. Similar findings were observed across genders and across patients with mood and psychotic disorders. The one item endorsed by more than 20% of the sample had a 23.7% overall endorsement rate and significantly different endorsement rates across ethnic groups, with the highest endorsements occurring among Hispanic/Latino (43.3% endorsement rate) patients. Endorsement rates of F-r items were generally higher than for Fp-r items. At the scale level, we also examined correlations with the Restructured Clinical Scales and found that Fp-r demonstrated lower correlations than F-r, indicating that Fp-r is less associated with a broad range of psychopathology. Finally, we found that Fp-r demonstrated slightly higher specificity values than F-r at all T score cutoffs. (PsycINFO Database Record PMID- 27414152 TI - Factor mixture modeling of intolerance of uncertainty. AB - Intolerance of uncertainty (IU) is a multidimensional construct that has been proposed as an important transdiagnostic risk factor across various anxiety and mood disorders. Recent work found support for IU having a continuous latent structure when utilizing taxometric methods. However, taxometrics may not be ideally suited to examine the latent structure of constructs such as IU given the methodological shortcomings associated with this technique. The current study applied factor mixture modeling, a statistical technique that overcomes shortcomings of prior work, to examine the latent structure of IU in a sample of 371 individuals presenting at an outpatient clinic. Findings indicated that the best fitting solution was a 3-class model with 1 class consisting of individuals with high levels of IU (High IU; n = 55) and 1 containing individuals with low levels of IU (Low IU; n = 206). Our third class, labeled Moderate IU, consisted of 110 individuals with levels of IU between those of the High IU and Low IU groups. There were also significant differences across the 3 IU classes, including the relations between IU classes and anxiety-related and depressive disorders. The current investigation was the first to find evidence of IU having a categorical latent structure. Implications for research and clinical utility are discussed. (PsycINFO Database Record PMID- 27414153 TI - Readiness of communities to engage with childhood obesity prevention initiatives in disadvantaged areas of Victoria, Australia. AB - Objective Disadvantaged communities bear a disproportionate burden of childhood obesity and show low participation in childhood obesity prevention initiatives. This study aims to examine the level of readiness of disadvantaged communities to engage with childhood obesity prevention initiatives. Methods Using the community readiness model, 95 semi-structured interviews were conducted among communities in four disadvantaged areas of Victoria, Australia. Community readiness analysis and paired t-tests were performed to assess the readiness levels of disadvantaged communities to engage with childhood obesity prevention initiatives. Results The results showed that disadvantaged communities demonstrated low levels of readiness (readiness score=4/9, 44%) to engage with the existing childhood obesity prevention initiatives, lacked knowledge of childhood obesity and its prevention, and reported facing challenges in initiating and sustaining participation in obesity prevention initiatives. Conclusion This study highlights the need to improve community readiness by addressing low obesity-related literacy levels among disadvantaged communities and by facilitating the capacity building of bicultural workers to deliver obesity prevention messages to these communities. Integrating these needs into existing Australian health policy and practice is of paramount importance for reducing obesity-related disparities currently prevailing in Australia. What is known about the topic? Childhood obesity prevalence is plateauing in developed countries including Australia; however, obesity-related inequalities continue to exist in Australia especially among communities living in disadvantaged areas, which experience poor engagement in childhood obesity prevention initiatives. Studies in the USA have found that assessing disadvantaged communities' readiness to participate in health programs is a critical initial step in reducing the disproportionate obesity burden among these communities. However, no studies in Australia have assessed disadvantaged communities' readiness to engage in obesity prevention initiatives. What does this paper add? This paper addresses the current gap in the knowledge of disadvantaged communities' level of readiness to engage in childhood obesity prevention initiatives in Australia. The study also identified the key factors responsible for low readiness of disadvantaged communities to participate in current childhood obesity prevention services. By using the Community Readiness model this study shows the readiness levels specific to the various dimensions of the model; Understanding dimension-specific readiness allows us to identify strategies that are tailored to each dimension, as guided by the model. What are the implications for practitioners? With the increasing burden of childhood obesity on disadvantaged communities, policymakers and health practitioners are facing a crisis in obesity prevention and management. Almost every year, new interventions are being planned and implemented. However if the target communities are not ready to participate in the available interventions these efforts are futile. This study exposes the key factors responsible for low readiness to participate in current obesity prevention services by disadvantaged communities. Addressing these key factors and improving readiness before designing new interventions will improve the participation of disadvantaged communities in those interventions. The study findings ultimately have the potential of reducing obesity-related disparities in Australia. PMID- 27414154 TI - Transversus Abdominis Muscle Release: Innovations in Technique Can Still Happen. PMID- 27414155 TI - Chronic Kidney Disease Class Predicts Mortality After Abdominal Aortic Aneurysm Repair in Propensity-matched Cohorts From the Medicare Population. AB - INTRODUCTION: Chronic kidney disease (CKD) predicts mortality after abdominal aortic aneurysm (AAA) repair. Few studies are adequately powered to stratify outcomes by CKD severity. This study assesses the effect of CKD severity on survival after AAA repair. METHODS: Patients who underwent AAA repair from 2006 to 2007 were retrospectively identified in the Medicare database and stratified by CKD class as follows: normal (CKD class 1 and 2), moderate (CKD class 3), and severe (CKD class 4 and 5). Propensity matching (30:1) by clinical factors and procedure type was performed to derive well-matched comparative cohorts. Primary outcomes were 30-day and long-term mortality; secondary outcomes included hospital length of stay and cost. RESULTS: A total of 47,715 patients were included (96.7% normal, 1.88% moderate, and 1.65% severe). Propensity matching was corrected for differences between cohorts. Thirty-day mortality was higher in moderate (5.7% vs normal 2.5%; P < 0.01) and severe (9.9% vs normal 1.8%; P < 0.01) groups. Hospital length of stay increased with CKD severity (4.4 +/- 3.7 days normal vs 6.5 +/- 4.2 days moderate CKD; P < 0.01/4.7 +/- 3.8 days normal vs 9.1 +/- 4.5 days severe CKD; P < 0.01) as did cost ($23 +/- 14K normal vs $25 +/- 16K moderate; P < 0.01 /$22 +/- 11K normal vs $29 +/- 22K severe; P < 0.01). Three-year survival favored the normal cohort (80% vs 64% moderate; log rank P < 0.01 /82% normal vs 44% severe; log rank P < 0.01). CONCLUSIONS: CKD severity is an important predictor of perioperative mortality and long-term survival after AAA repair in propensity-matched cohorts. The 5-fold increase in 30-day mortality and 44% in 3-year survival suggest that elective AAA repair is contraindicated in most severe CKD patients. PMID- 27414157 TI - Addition of RAS Mutation Status May Strengthen the Predictive Model for Progression of Indeterminate Pulmonary Nodules. PMID- 27414158 TI - Single Cell Peptide Heterogeneity of Rat Islets of Langerhans. AB - Measuring the chemical composition of individual cells in mammalian organs can provide critical insights toward understanding the mechanisms leading to their normal and pathological function. In this work, single cell heterogeneity of islets of Langerhans is characterized with high throughput by microscopy-guided single cell matrix-assisted laser desorption/ionization mass spectrometry. Two levels of chemical heterogeneity were observed from the analysis of more than 3000 individual cells. Within a single islet, cellular heterogeneity was evident from the exclusive expression of the canonical biomarkers glucagon, insulin, pancreatic polypeptide (PP), and somatostatin within alpha-, beta-, gamma-, and delta-cells, respectively. We localized the neuropeptide WE-14, a known cell-to cell signaling molecule, to individual delta-cells. Moreover, several unreported endogenous peptides generated by dibasic site cleavages of PP were detected within individual gamma-cells. Of these, PP(27-36) was previously shown to activate the human Y4 receptor, suggesting it has a signaling role in vivo. Heterogeneity in cell composition was also observed between islets as evidenced by a 50-fold larger alpha-cell population in islets of the dorsal pancreas compared to the ventral-derived pancreatic islets. Finally, PP(27-36) was more abundant in gamma-cells from the ventral region of the pancreas, indicating differences in the extent of PP-prohormone processing in the two regions of the pancreas. PMID- 27414159 TI - Sildenafil does not Improve Exercise Capacity under Acute Hypoxia Exposure. AB - The increase in pulmonary arterial pressure (PAP) due to hypoxic pulmonary vasoconstriction (HPV) could be a limiting factor for physical performance during hypoxic exposure. Sildenafil has been shown to reduce PAP in situations of moderate or severe hypoxia, and consequently its role as an ergogenic aid and even a possible doping substance must be considered. We performed a double-blind crossover study to determine the effects of sildenafil on cardiovascular, respiratory and metabolic parameters in normoxia and during acute exposure to hypobaric hypoxia (4 000 m) at rest and during maximal and submaximal (60% VO2 max) exercise tests. One hour before testing started, sildenafil (100 mg) or a placebo was orally administered to 11 volunteers. In normoxic conditions, sildenafil did not affect performance. Similarly, no significant differences were found in cardiovascular and respiratory parameters in hypoxic conditions at rest or during exercise. The use of sildenafil to improve physical performance in non acclimatized subjects is not supported by our data. PMID- 27414160 TI - Structural Analysis of Hydrophobe-Uptake Micelle of an Amphiphilic Alternating Copolymer in Aqueous Solution. AB - We investigated the structure of the hydrophobe-uptake micelle of an alternating amphiphilic copolymer in aqueous solutions, by combining light scattering and small-angle X-ray scattering (SAXS). When the copolymer micelle includes the hydrophobe (1-dodecanol), the unicore flower micelle transforms into the multicore flower necklace, and the flower necklace is slightly stiffer than the hydrophobe-free flower necklace of the same copolymer. Moreover, the hydrophobe is included not in the hydrophobic core region but in the intermingled region of the hydrophobic group and the loop chain of the unit flower micelle. Therefore, the structure of the hydrophobe-uptake micelle of the amphiphilic alternating copolymer is quite different from that of hydrophobe-uptake spherical micelles of low molar mass surfactants and of amphiphilic block copolymers, where the hydrophobe is included in the hydrophobic region of the micelles. PMID- 27414161 TI - Control of Multipolar and Orbital Order in Perovskite-like [C(NH2)3]CuxCd1 x(HCOO)3 Metal-Organic Frameworks. AB - We study the compositional dependence of molecular orientation (multipolar) and orbital (quadrupolar) order in the perovskite-like metal-organic frameworks [C(NH2)3]CuxCd1-x(HCOO)3. Upon increasing the fraction x of Jahn-Teller-active Cu(2+), we observe an orbital disorder/order transition and a multipolar reorientation transition, each occurring at distinct critical compositions xo = 0.45(5) and xm = 0.55(5). We attribute these transitions to a combination of size, charge distribution, and percolation effects. Our results establish the accessibility in formate perovskites of novel structural degrees of freedom beyond the familiar dipolar terms responsible for (anti)ferroelectric order. We discuss the implications of cooperative quadrupolar and multipolar states for the design of relaxor-like hybrid perovskites. PMID- 27414162 TI - Effects of Syndiotacticity on the Dynamic and Static Phase Separation Properties of Poly(N-isopropylacrylamide) in Aqueous Solution. AB - The dynamic and static phase separation behavior in aqueous poly(N isopropylacrylamide) (PNIPAM) solutions is highly sensitive to the tacticity of PNIPAM. We investigated the phase separation dynamics of aqueous solutions of PNIPAM with different tacticities (atactic and syndiotactic-rich types) and found that the phase separation dynamics of syndiotactic-rich PNIPAM was much different from that of atactic-type PNIPAM. First, phase separation in syndiotactic-rich PNIPAM was faster. Second, there was a critical point (Ccp) in the concentration dependence of the phase separation rate: the phase separation accelerated dramatically when the solution concentration was higher than 2.0 wt % (= Ccp). Third, syndiotactic-rich PNIPAM required a higher thermal energy for phase separation compared to atactic PNIPAM. Such behavior can be explained on the basis of the high hydrophobicity of syndiotactic-rich PNIPAM in a dehydrated state and a diffusion-controlled aggregation model. The present study shows that precise control of the stereoregularity will open new channels toward the design and development of stimuli-responsive-polymer-based smart materials. PMID- 27414163 TI - Soft-mode of charged chiral fibrous viruses (fd). AB - The frictional forces in suspensions vary depending on the size, shape, and the surface of the particles, which are either charged or neutral. For anisotropic particles with no spatial gradient in the order parameter under external parameters, they exhibit either a continuous phase transition or "freezing" of the order parameter fluctuation. They are known as the collective soft-mode, which has a finite cutoff dispersion where the relaxation time diverges. From microscopic dynamics of charged chiral fd-viruses, the soft-mode is revealed with a rotation restoring "twist", obtained from both polarized (VV) and depolarized (VH) small angle dynamic light scattering. Here, I have found the minimum spatial coherence length at a lower I-N binodal concentration, which is due to the reverse of electrostatic repulsive forces with an increase in the concentration of charged chiral rods. PMID- 27414164 TI - Correction to Bioactive Enmein-Type ent-Kaurane Diterpenoids from Isodon phyllostachys. PMID- 27414166 TI - Notes from the Field: Acute Sulfuryl Fluoride Poisoning in a Family - Florida, August 2015. AB - On August 19, 2015, the Florida Department of Health (FDOH) was notified by the Florida Poison Information Center Network and a local hospital of possible sulfuryl fluoride poisonings affecting a family in Martin County, in southeastern Florida. Sulfuryl fluoride is a highly toxic (toxicity category I) gas fumigant used for termite control of homes and buildings.* FDOH personnel in Martin County commenced an investigation and identified a family of five (a grandmother, mother, father, son, and daughter) exposed to sulfuryl fluoride after their house was fumigated. The Florida Department of Agriculture and Consumer Services (FDACS), and the U.S. Environmental Protection Agency (EPA) Criminal Investigation Division also conducted an investigation after being notified by FDOH. Medical records were reviewed, and the father was interviewed by FDOH. PMID- 27414167 TI - Emulsion-Based RIR-MAPLE Deposition of Conjugated Polymers: Primary Solvent Effect and Its Implications on Organic Solar Cell Performance. AB - Emulsion-based, resonant infrared matrix-assisted pulsed laser evaporation (RIR MAPLE) has been demonstrated as an alternative technique to deposit conjugated polymer films for photovoltaic applications; yet, a fundamental understanding of how the emulsion target characteristics translate into film properties and solar cell performance is unclear. Such understanding is crucial to enable the rational improvement of organic solar cell (OSC) efficiency and to realize the expected advantages of emulsion-based RIR-MAPLE for OSC fabrication. In this paper, the effect of the primary solvent used in the emulsion target is studied, both experimentally and theoretically, and it is found to determine the conjugated polymer cluster size in the emulsion as well as surface roughness and internal morphology of resulting polymer films. By using a primary solvent with low solubility-in-water and low vapor pressure, the surface roughness of deposited P3HT and PCPDTBT polymer films was reduced to 10 nm, and the efficiency of P3HT:PC61BM OSCs was increased to 3.2% (~100 times higher compared to the first MAPLE OSC demonstration [ Caricato , A. P. ; Appl. Phys. Lett. 2012 , 100 , 073306 ]). This work unveils the mechanism of polymer film formation using emulsion-based RIR-MAPLE and provides insight and direction to determine the best ways to take advantage of the emulsion target approach to control film properties for different applications. PMID- 27414168 TI - Consequences of ET and MMCT on Luminescence of Ce(3+)-, Eu(3+)-, and Tb(3+)-doped LiYSiO4. AB - Ce(3+), Eu(3+), and Tb(3+) singly doped, Ce(3+)-Tb(3+), Tb(3+)-Eu(3+), and Ce(3+) Eu(3+) doubly doped, as well as Ce(3+)-Tb(3+)-Eu(3+) triply doped LiYSiO4 phosphors were prepared by a high-temperature solid-state reaction technique. Rietveld refinement was performed to determine the structure of host compound. The cross-relaxation (CR) of Tb(3+) is quantitatively analyzed with the Inokuti Hirayama model of energy transfer (ET), and the site occupancy is confirmed by emission spectra of Eu(3+). ET and metal-metal charge transfer (MMCT) are systematically investigated in Ce(3+)-Tb(3+), Tb(3+)-Eu(3+), and Ce(3+)-Eu(3+) doubly doped systems. The combined effects of ET and MMCT on luminescence and emission color of Ce(3+)-Tb(3+)-Eu(3+) triply doped samples are discussed in detail, showing that the photoluminescence emission is tunable in a large color gamut. PMID- 27414169 TI - Peer review: the process. PMID- 27414170 TI - Don't panic! Electronic submissions to Redox Report. PMID- 27414171 TI - Vitamin C: the key to health or a slow-acting carcinogen? PMID- 27414172 TI - Effects of oxidants and antioxidants evaluated using parinaric acid as a sensitive probe for oxidative stress. AB - Parinaric acid (PnA) is a fluorescent polyunsaturated fatty acid which can be used as a probe to study lipid peroxidation processes. The basic methodology is simple and sensitive, and offers a direct 'view' of the oxidative decay of a fatty acid and the effects of prooxidant and antioxidant factors. A distinctive feature of the PnA assay is that it does not measure a lipid peroxidation end product, but monitors lipid oxidative stress in its initial stages. This review highlights the methodological characteristics of the PnA assay, and describes the various applications in which PnA and PnA derivatives have yielded useful information. These applications range from oxidant and antioxidant studies in lipid model systems to comparative studies of oxidation processes in normal and pathological red blood cells, and also include studies of lipoprotein oxidation. PMID- 27414173 TI - Transcriptional regulators of the oxidative stress response in prokaryotes and eukaryotes. AB - Bacteria, yeast and cells of higher eukaryotes specifically induce the expression of genes encoding antioxidant defenses when exposed to reactive oxygen species. Recent studies have also suggested that reactive oxygen intermediates play a role as second messengers in signal transduction pathways. Therefore, cells must possess regulators that sense oxidant signals and transduce the signals into changes in gene expression. This review provides an overview of the transcription factors in Escherichia coli, Saccharomyces cerevisiae and mammalian cells that govern the response to oxidative stress. Some of the regulators function primarily as regulators of antioxidant genes while other regulators of the oxidative stress response also regulate genes important for metal homeostasis or cell metabolism during aerobic or anaerobic growth. PMID- 27414174 TI - Role of metal-catalyzed autoxidation in Maillard reaction damage to proteins in vivo. PMID- 27414175 TI - Comments on the role of metal-catalysed autoxidation in glycation and the Maillard reaction. PMID- 27414176 TI - Neutrophils and oxygen-induced lung injury: a case of when a few is still too many. AB - The role of neutrophils in acute oxidative lung injury in preterm babies is presently unclear, with some investigators maintaining they contribute to tissue injury while others believe they do not. The aim of the present study was to determine whether neutropenia, induced by a specific neutrophil antibody, influenced the time course or extent of oxygen-induced injury of the immature lung. Preterm guinea pigs, delivered by caesarean section at 65 days' gestation (term=68 days), were injected intraperitoneally with either control serum (CS) or neutrophil antiserum (NAS; 200 MUl/100 g body weight) once daily for 5 days. Pups were exposed to 95% oxygen for the first 72 h, and then allowed to recover in 21% oxygen for the subsequent 48 h. Groups of treated animals were also maintained in 21% oxygen for 5 days. Lungs were examined by bronchoalveolar lavage (BAL) at 72 h or 120 h. In CS-treated pups, exposure to 95% oxygen increased both the number of circulating neutrophils and those recovered by BAL at both 72 h and 120 h. Protein concentration in BAL fluid, an index of lung microvascular permeability, and BAL elastase and beta-glucuronidase activities, indices of neutrophil activation, were significantly increased in pups exposed to 95% oxygen. Pups exposed to 95% oxygen and treated with NAS showed a decrease in numbers of circulating neutrophils (72 h, 9.53 vs 0.66 x 10(5)/ml, P<0.0005; 120 h, 4.9 vs 0.08 x 10(5)/ml, P<0.0005) and BAL fluid neutrophils (72 h, 3.1 vs 0.7 x 10(5)/ml, P<0.05; 120 h, 12.4 vs 3.8 x 10(5)/ml, P<0.05). BAL protein concentration, neutrophil elastase and beta-glucuronidase activities in hyperoxia exposed pups were similar following treatment with either CS or NAS. Although the number of circulating neutrophils were markedly depleted and expansion of the alveolar neutrophil pool was restricted in NAS-treated pups, the neutrophils recruited to the lung were activated and could have contributed to the increase in microvascular permeability in hyperoxia-exposed pups. PMID- 27414177 TI - Biological variation of ascorbic acid and alpha-tocopherol. AB - Accumulating evidence that free radicals may contribute to various diseases, has sparked epidemiological and experimental studies of the correlation between plasma levels of antioxidant vitamins and risk to develop cancer, ischaemic heart disease and stroke. These studies often do not take into account the random biological fluctuation of the antioxidant concentration, which occurs in each individual. The weekly and monthly variability of the antioxidants ascorbic acid and alpha-tocopherol was studied in 12 healthy volunteers (4 women and 8 men) aged 23-45 years. Vitamin levels were determined using high performance liquid chromatography. Over 12 weeks the mean plasma concentration of ascorbic acid was 42+/- 12 MUmol/I and of alpha-tocopherol was 31+/-3 MUmol/I. The intraindividual coefficients of variation (estimated using analysis of variance techniques) were 26% (ascorbic acid) and 12% (alpha-tocopherol). The analytical goal for imprecision was achieved for both vitamins, i.e. it was less than one-half of the measured intraindividual variation. Both antioxidants showed marked individuality, indicating that an individual's reference values are more useful than population-based data. The critical difference required for significance of changes in serial results is smaller for alpha-tocopherol (34%) than that for ascorbic acid (72%). PMID- 27414178 TI - Tissue-specific susceptibility to peroxyl radical-mediated inhibition of mitochondrial transcription. AB - Proper mitochondrial function requires the continual maintenance of the integrity of the mitochondrial gene expression system. We have recently shown, using rat liver mitochondria, that the mitochondrial transcription system is extremely sensitive to inhibition by peroxyl radicals. In this report, we demonstrate that the transcription process in mitochondria isolated from rat heart and brain are more resistant to this oxidative insult than is the transcription machinery in liver mitochondria. This finding is in contrast to the generally observed trend that liver and liver mitochondria are equally or better protected against oxidative stress, and highlights the differential oxidant-specific anti-radical defenses in mitochondria isolated from these tissues. Finally, in conjunction with previous data, these results demonstrate the existence of a potent, tissue specific anti-radical resistance capacity that protects the mitochondrial gene expression system. PMID- 27414179 TI - N-acetylcysteine prevents TNF-induced mitochondrial damage, apoptosis and viral particle production in HIV-infected U937 cells. AB - It has been hypothesized that reactive oxygen intermediates (ROI) can activate human immunodeficiency virus (HIV) replication and that HIV can trigger programmed cell death (PCD). In this work, we studied PCD in U937 cultured cells chronically infected with HIV and exposed to tumor necrosis factor alpha (TNFalpha). This cytokine has been shown to induce apoptosis in some cell types and to produce intracellular free radical species including ROI. In addition, it was also demonstrated that HIV-induced PCD observable in U937 infected cells can be favored by TNF exposure. In one of our recent works, evidence was presented that the thiol supplier N-acetylcysteine (NAC) can 'protect', at least partially, HIV-infected cells from PCD and determine a significant decrease in viral progeny. In the present work, we demonstrate (a) that apoptosis can be easily induced by TNF only in infected U937 cells and not in control wild-type cells, (b) that daily treatment of TNF-exposed cells with low concentrations of NAC is able to impair viral progeny formation as early as 24 h, (c) that the mitochondrial damage induced by TNF is counteracted by preexposure to NAC, and (d) that NAC alone exerts changes in mitochondria which may be responsible for the protective effects exerted by this compound. Because of the radical producing capacity of TNF, these results seem to indicate that the protective effects of NAC may be due to the specific antioxidant nature of this substance which appears to be capable of impairing both the apoptotic machinery and viral replication by an intracellular mechanism involving mitochondrial integrity and function. PMID- 27414180 TI - Formation of reactive oxygen species during one-electron reduction of noradrenochrome catalyzed by NADPH-cytochrome P-450 reductase. AB - One-electron reduction of noradrenochrome catalyzed by NADPH-cytochrome P-450 reductase resulted primarily in the formation of o-semiquinone and, probably, also o-hydroquinone. Under aerobic conditions these reduced form(s) autoxidize, accompanied by the formation of reactive oxygen species, as revealed by continuous NADPH oxidation and oxygen consumption. The presence of manganese pyrophosphate complex contributed to autoxidation of the o-semiquinone during the reduction of noradrenochrome catalyzed by NADPH-cytochrome P-450 reductase, since the addition of the metal chelator diethylenetriamine pentaacetic acid (DETAPAC) resulted in a 34% inhibition of NADPH oxidation. Oxygen in the ground state was found to be predominantly involved in the autoxidation of o-semiquinone during the reduction of noradrenochrome catalyzed by NADPH-cytocbrome P-450 reductase, since the addition of superoxide dismutase (SOD) to the incubation mixture only inhibited NADPH oxidation 13% and 6% in the absence and presence of DETAPAC, respectively. The addition of catalase to the incubation mixture resulted in a slight increase in NADPH oxidation, both in the absence and in the presence of diethylenetriamine pentaacetic acid. However, no effect of catalase and SOD together on NADPH oxidation was observed, either in the absence or presence of DETAPAC. PMID- 27414181 TI - Steady magnetic fields effect on lipid peroxidation kinetics. AB - The effect of steady magnetic fields (ranging from 0 to 280 mT) has been investigated on the kinetics of non-enzymatic lipid peroxidation occurring in a model system consisting of liposomes obtained from 1, 2 dioleoylphosphatidylcholine by oxygen consumption. The process was found to be accelerated by weak steady magnetic fields. A computer simulation method was employed to detect the reactions that govern the process kinetics, to elucidate magneto-sensitive stages (initiation and reduction of iron(III), as well as lipid peroxide radical recombination) and to determine their rate constants at various external magnetic fields. The kinetics of peroxidation of lipid cell membranes have been modeled mathematically at oxygen and 'free' iron concentrations close to those in the cells and also at increased free iron concentrations at different external magnetic field values. PMID- 27414182 TI - Single CdTe Nanowire Optical Correlator for Femtojoule Pulses. AB - On the basis of the transverse second harmonic generation (TSHG) in a highly nonlinear subwavelength-diameter CdTe nanowire, we demonstrate a single-nanowire optical correlator for femto-second pulse measurement with pulse energy down to femtojoule (fJ) level. Pulses to be measured were equally split and coupled into two ends of a suspending nanowire via tapered optical fibers. The couterpropagating pulses meet each other around the central area of the nanowire, and emit TSHG signal perpendicular to the axis of the nanowire. By transferring the spatial intensity profile of the transverse second harmonic (TSH) image into the time-domain temporal profile of the input pulses, we operate the nanowire as a miniaturized optical correlator. Benefitted from the high nonlinearity and the very small effective mode area of the waveguiding CdTe nanowire, the input energy of the single-nanowire correlator can go down to fJ-level (e.g., 2 fJ/pulse for 1064 nm 200 fs pulses). The miniature fJ-pulse correlator may find applications from low power on-chip optical communication, biophotonics to ultracompact laser spectroscopy. PMID- 27414183 TI - In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium competitive acid blocker. AB - 1. TAK-438, vonoprazan fumarate, is a novel orally active potassium-competitive acid blocker, developed as an antisecretory drug. In this study, we investigated the in vitro metabolism of 14C-labeled TAK-438. In human hepatocytes, M-I, M-II, M-III and M-IV-Sul were mainly formed, and these were also detected in clinical studies. N-demethylated TAK-438 was also formed as an in vitro specific metabolite. Furthermore, CYP3A4 mainly contributed to the metabolism of TAK-438 to M-I, M-III, and N-demethylated TAK-438, and CYP2B6, CYP2C19 and CYP2D6 partly catalyzed the metabolism of TAK-438. The sulfate conjugation by SULT2A1 also contributed to the metabolism of TAK-438 to form TAK-438 N-sulfate, and CYP2C9 mediated the formation of M-IV-Sul from TAK-438 N-sulfate. The metabolite M-IV, which could be another possible intermediate in the formation of M-IV-Sul, was not observed as a primary metabolite of TAK-438 in any of the in vitro studies. 2. In conclusion, TAK-438 was primarily metabolized by multiple metabolizing enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, and a non-CYP enzyme SULT2A1, and the influence of the CYP2C19 genotype status on gastric acid suppression post TAK-438 dosing could be small. The multiple metabolic pathways could also minimize the effects of co-administrated CYP inhibitors or inducers on the pharmacokinetics of TAK-438. PMID- 27414184 TI - Age-related cognitive decline as a function of daytime testing. AB - The current study investigates the effects of age, cognitive load, optimal time of-day testing, and irrelevant background noise suppression on mental processing. One hundred and seventy-eight young (M = 22.97 years) and 114 old adults (M = 56.38 years) were assessed for implicit learning and speed of information processing under irrelevant sound interference early during daytime (7AM-2.30PM) or in the afternoons (3PM-midnight). No direct effect of irrelevant speech effect was found on implicit learning. An optimal time of testing per age group was identified according to the ability to suppress irrelevant auditory information. If no semantic meaning was derived from the sound conditions, irrelevant sound was easily inhibited leaving no room for declined cognitive performance. This suggests an intact phonological inhibition in older adults and a further circumvention of the phonological loop. However, when difficulty was increased, a widened performance gap between young and old people could be observed. Education modulated difficult performance irrespective of age. With increasing age, task demand fulfillment becomes a function of a limited time mechanism. If extraneous time is not adapted to cognitive skills and performance, higher order processing cannot be reached, rendering older adults slower than their younger counterparts. PMID- 27414185 TI - Jack Caldwell 1928-2016. PMID- 27414188 TI - The Hematopoietic Microenvironment. PMID- 27414186 TI - An investigation of the unexpectedly high fertility of secular, native-born Jews in Israel. AB - Secular, native-born Jews in Israel enjoy the socio-economic status of many affluent populations living in other democratic countries, but have above replacement period and cohort fertility. This study revealed a constellation of interrelated factors which together characterize the socio-economic, cultural, and political environment of this fertility behaviour and set it apart from that of other advanced societies. The factors are: a combination of state and family support for childbearing; a dual emphasis on the social importance of women's employment and fertility; policies that support working mothers within a conservative welfare regime; a family system in which parents provide significant financial and caregiving aid to their adult children; relatively egalitarian gender-role attitudes and household behaviour; the continuing importance of familist ideology and of marriage as a social institution; the role of Jewish nationalism and collective behaviour in a religious society characterized by ethno-national conflict; and a discourse which defines women as the biological reproducers of the nation. Supplementary material for this article is available at: http://dx.doi.org/10.1080/00324728.2016.1195913. PMID- 27414187 TI - Anticipatory affect during action preparation: evidence from backward compatibility in dual-task performance. AB - Upcoming responses in the second of two subsequently performed tasks can speed up compatible responses in the temporally preceding first task. Two experiments extend previous demonstration of such backward compatibility to affective features: responses to affective stimuli were faster in Task 1 when an affectively compatible response effect was anticipated for Task 2. This emotional backward-compatibility effect demonstrates that representations of the affective consequences of the Task 2 response were activated before the selection of a response in Task 1 was completed. This finding is problematic for the assumption of a serial stimulus-response translation stage. It also shows that the affective consequence of a response is anticipated during, and has an impact on stimulus response translation, which implies that action planning considers codes representing and predicting the emotional consequences of actions. Implications for the control of emotional actions are discussed. PMID- 27414189 TI - Editorial Comment: Heterogeneity of Bone Marrow Stromal Cells Editorial Comment on Dr. Waller's Paper. PMID- 27414190 TI - Pyruvate Kinase Deficiency which Causes Nonspherocytic Hemolytic Anemia: The Gene and its Mutations. PMID- 27414192 TI - Rising Concern Regarding Pregnant Women and Zika Virus. PMID- 27414193 TI - STK33 potentiates the malignancy of hypopharyngeal squamous carcinoma: Possible relation to calcium. AB - BACKGROUND: The present study aims to further explore the role of STK33 in hypopharyngeal squamous cell carcinoma (HSCC), with special attention given to the possible relationship between STK33 alteration and calcium. METHODS: An in vivo experiment and microarray analysis were performed to investigate the impact of STK33 knockdown (STK33-RNAi) on the biological behaviors and the gene profile alterations of a HSCC cell line (Fadu). Cell viability and morphological change of Fadu cells in response to Ionomycin were measured by MTT assay and acridine orange staining. The concentration of intracellular calcium ([Ca(2+)]i) was detected by laser scanning confocal microscope with fluo-3/AM. The mRNA and protein expressions of relevant genes were examined by real-time PCR and Western blot. RESULTS: STK33-RNAi retarded the Fadu cell proliferation and the metastasis in nude mice and led to up- and down-regulation of the expressions of abundance of genes, especially, the downregulation of the CAPN1 gene. Ionomycin increased the [Ca(2+)]i and decreased the survival rates of Fadu cells in a time-dependent manner. Moreover, Ionomycin resulted in the elevation of CAPN1 mRNA expression in normal Fadu cells and, conversely, had almost no effect on CAPN1 expression in STK33-RNAi cells. CONCLUSIONS: Findings from this work further validate that STK33 is a potential oncogene and plays an important role in tumorigenesis of HSCC via regulation of numerous genes. In addition, there exists the reciprocal influence between STK33 and [Ca(2+)]i in Fadu cells. PMID- 27414195 TI - Elastin-like polypeptides: the power of design for smart cell encapsulation. AB - INTRODUCTION: Cell encapsulation technology is still a challenging issue. Innovative methodologies such as additive manufacturing, and alternative bioprocesses, such as cell therapeutic delivery, where cell encapsulation is a key tool are rapidly gaining importance for their potential in regenerative medicine. Responsive materials such as elastin-based recombinant expression products have features that are particularly attractive for cell encapsulation. They can be designed and tailored to meet desired requirements. Thus, they represent promising candidates for the development of new concept-based materials that can be employed in this field. Areas covered: An overview of the design and employment of elastin-like polypeptides for cell encapsulation is given to outline the state of the art. Special attention is paid to the design of the macromolecule employed as well as to the method of matrix formation and the biological system involved. Expert opinion: As a result of recent progress in regenerative medicine there is a compelling need for materials that provide specific properties and demonstrate defined functional features. Rationally designed materials that may adapt according to applied external stimuli and that are responsive to biological systems, such as elastin-like polypeptides, belong to this class of smart material. A run through the components described to date represents a good starting point for further advancement in this area. Employment of these components in cell encapsulation application will promote its advance toward 'smart cell encapsulation technology'. PMID- 27414194 TI - Bone and metal targeted polymeric nanoparticles (US20150125391 A1): a patent evaluation. AB - INTRODUCTION: Delivery of therapeutic agents to bone is crucial for the treatment of bone metastasis and other bone diseases. The present invention patent relates to bone- and metal-targeted polymeric nanoparticles for targeting delivery of therapeutic molecules to the pathological tissues in bone or the surgical metal implant-bone tissue interface. AREAS COVERED: The nanoparticles for drug delivery were fabricated via the assembly of amphiphilic polymers, in which the hydrophilic outer layer was minimal to prolong the circulation time, and the hydrophobic insider core was biodegradable and loaded with therapeutic agents. Bone-targeted elements were conjugated on the nanoparticle surface to enhance their affinity to bone and/or metal implant surface. EXPERT OPINION: A prolonged, sustained release of therapeutic agents was observed by using the delivery system targeting to bone. The described invention provides a bone-targeted vector to deliver diverse therapeutic agents to bone. PMID- 27414197 TI - Coming in postgraduate medicine. PMID- 27414196 TI - Predictors of college-student food security and fruit and vegetable intake differ by housing type. AB - OBJECTIVE: We assessed whether college-student characteristics associate with food security and fruit and vegetable (FV) intake and whether these associations differ in students in housing with and without food provision. PARTICIPANTS: 514 randomly-sampled students from a large, Midwestern, public university in 2012 and 2013 METHODS: Ordered logistic regression tested how student characteristics associate with food security. Linear regression tested how student characteristics associate with FV intake. Analyses were stratified by housing type - that is, housing with food provision (dormitory, fraternity/sorority house, cooperative) vs. housing without food provision. RESULTS: Only among those living in housing without food provision, males (p = 0.04), students without car access (p = 0.005), and those with marginal (p = 0.001) or low (p = 0.001) food security demonstrated lower FV intake. CONCLUSIONS: Housing with food provision may buffer the effects of student characteristics on food. PMID- 27414198 TI - Editor's mail. PMID- 27414199 TI - Problems solutions. PMID- 27414200 TI - What's happening in medicine. PMID- 27414201 TI - Washington background. PMID- 27414203 TI - ENT Self-Test. PMID- 27414202 TI - External Otitis. PMID- 27414204 TI - ReadySource on ENT for the Nonspecialist. PMID- 27414206 TI - Therapeutic Index to Advertisers. PMID- 27414207 TI - A Combination Therapy with Baicalein and Taxol Promotes Mitochondria-Mediated Cell Apoptosis: Involving in Akt/beta-Catenin Signaling Pathway. AB - Baicalein, a major flavonoid, possesses anticancer and anti-inflammatory activity. The aim of the study is to explore the efficiency of combination therapy with baicalein and taxol, as well as the molecular mechanism on antitumor activity. Human ovarian cancer cells were treated with different concentration of baicalein for 48 h, and cell viability was determined by MTT assay. Baicalein inhibited cell proliferation of ovarian cancer cells, and IC50 value of baicalein in A2780 cells, SKOV3 cells, and OVCAR cells was 46.23, 60.68, and 38.03 MUM, respectively. The ovarian cancer cells were treated with 10 MUM of baicalein combined with increasing concentration of taxol for 48 h, and the results demonstrated that combination therapy with baicalein and taxol had much higher antitumor effects compared with the monotherapy. The molecular mechanisms involving in combination therapy promoted the caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase, which increased the cell apoptosis of ovarian cancer cells. Moreover, Z-VAD-FMK treatment partially decreased the baicalein-induced proliferation inhibition in human ovarian cancer cells. Furthermore, baicalein induced apoptosis through activation of the activities of caspase-3,-9, and increased cytoplasmic cytochrome C release. Importantly, baicalein inhibited the growth of A2780 cells by inhibiting Akt/beta-catenin signaling pathway. In conclusion, our result revealed that baicalein combinated with taxol at low concentrations could exert synergistic antitumor effects in ovarian cancer cells through mitochondria-mediated cell apoptosis and Akt/beta catenin signaling pathway. Baicalein has a promising potential to be developed as an antitumor compound, and combination therapy of baicalein and taxol exhibits an antitumor potential in clinical therapy for human ovarian cancers. PMID- 27414208 TI - Bronchocutaneous Fistula without Pneumothorax after Intercostal Chest Drain Placement. PMID- 27414209 TI - Children's exposure to intimate partner violence: an overview. AB - Children's exposure to intimate partner violence (IPV) is associated with significant emotional impairment and other harmful effects. It is increasingly recognized as a type of child maltreatment, with outcomes similar to other types of abuse and neglect. Children can experience harm from exposure to IPV, even when not directly involved in, or a witness to, the violence between caregivers. This review, based on a synthesis of best available evidence, addresses the epidemiology of children's exposure to IPV, including prevalence, risk and protective factors, and associated impairment, as well as strategies for identification, and interventions for prevention of exposure and impairment. Strategies for ensuring children's safety are also discussed. The article concludes with guidance specific to mental health clinicians. PMID- 27414211 TI - Watermelon stomach and colon in a patient with diffuse cutaneous systemic sclerosis. PMID- 27414210 TI - Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study. AB - AIM: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission. MATERIALS & METHODS: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups. RESULTS: Calprotectin was 4.3 (2.6-8.2; mg/l; median [interquartile range]) in the sepsis, 2.8 (1.6-4.4) in the postoperative and 0.7 (0.4-1.6) in the intoxication groups. Area under the receiver operating characteristic curve for sepsis versus intoxication group was: 0.95, for sepsis versus postoperative groups: 0.65 and for survivors versus nonsurvivors: 0.70. CONCLUSION: Calprotectin was a sensitive marker of systemic inflammation, is a potential sepsis marker and performed well as mortality predictor in this pilot study. PMID- 27414213 TI - Editor's notes. PMID- 27414212 TI - When plasmonics meets membrane technology. AB - In this review, we present the applications of thermoplasmonics in membrane processes. We discuss the influence of the heat capacity of the solvent, the amount of plasmonic nanoparticles in the membrane, the intensity of the light source and the transmembrane flow rate on the increase of permeability. Remarkably, thermoplasmonic effects do not involve any noticeable loss of membrane rejection. Herein, we consider application feasibilities, including application fields, requirements of feed, alternatives of light sources, promising thermoplasmonic nanoparticles and scaling up issues. PMID- 27414215 TI - Coming in sportsmedicine. PMID- 27414216 TI - Wrap-up. PMID- 27414218 TI - Guest Editorial. PMID- 27414219 TI - Scanning sports. PMID- 27414220 TI - Abdominal Pain in a Football Player. PMID- 27414221 TI - Intravascular Hemolysis in Aerobic Dancing: The Role of Floor Surface and Type of Routine. AB - In brief: The effect of aerobic dancing on intravascular hemolysis was studied in 65 healthy women (aged 18 to 50 years) who were assigned to one of four groups according to the type of routine performed and the hardness of the floor surface. All subjects participated in a 60-minute dance session; a subgroup participated in five successive 60-minute sessions with one hour of rest between sessions. Blood was tested for both groups before and after exercise; urine was tested similarly for the subgroup only. The findings indicated that intravascular hemolysis occurred and that it was influenced by the type of routine, hardness of the surface, and duration of dancing. However, the degree of hemolysis was small and unlikely to contribute to the development of anemia. PMID- 27414222 TI - Primary Care Sports Medicine in the University Setting. AB - In brief: With sports and exercise participation increasing, there is a growing need for physicians with training in sports medicine. At Michigan State University in East Lansing, several programs have been established to give physicians, residents, and medical students training opportunities in sports medicine. As part of the sports medicine program, five physicians from two medical schools provide regular care to 25 intercollegiate teams. They also see patients with sports-related health concerns in the sports medicine clinic. These training and treatment programs add a number of diverse responsibilities to the work load of the MSU physicians. PMID- 27414224 TI - Clinical Applications for Exercise. AB - In brief: The body adapts to regular exercise by making central and peripheral physiologic adjustments. Although exercise doesn't reverse pathologic changes, it may play a significant role in the management of certain diseases. Thus physicians can prescribe exercise as therapy. For example, exercise increases calorie consumption but conserves lean body mass, which is an important consideration in the management of obesity. Exercise also has been shown to lower blood pressure-a desirable outcome for patients with hypertension. Similarly, diabetic patients may benefit from regular exercise because it improves glucose tolerance. The author discusses these and other interactions between physiology and exercise and their application to treatment of specific diseases. PMID- 27414223 TI - Tibial Tubercle Avulsion. AB - In brief: Tibial tubercle avulsion is an uncommon injury that has a peak incidence in early adolescence near the time of physeal closure. Because growth arrest and deformation can follow this injury, immediate diagnosis and treatment are essential. In this case a 14-year-old boy sustained a type 2 tibial tubercle avulsion while playing basketball and could not walk without assistance. Closed reduction was not possible because of soft-tissue interposition. PMID- 27414225 TI - Differentiating Between Meniscal and Patellar Pain. AB - In brief: Knee pain is the most common problem afflicting runners and recreational athletes. Two of the most common injury sites are at the patella and the meniscus; determining which is involved is central to providing effective treatment and helping patients resume normal activities with minimal delay. Subjective factors such as ability to get into and out of a squatting position provide valuable clues to meniscal vs patellar involvement. Objective factors such as anatomic knee variations do likewise. PMID- 27414226 TI - Golfers Use Exercise to Get Back in the Swing. AB - Professional golfer Payne Stewart's game was interrupted by a wear-and-tear injury to his back last January. But through an exercise program emphasizing trunk control and strength-a program that would benefit all golfers-Stewart was able to quickly return to the course. PMID- 27414228 TI - Sports Medicine Fellowships for Primary Care Physicians. PMID- 27414227 TI - Erythropoietin: A Dangerous New Form of Blood Doping? AB - Physicians are concerned that some endurance athletes may experiment with the new drug erythropoietin in an attempt to gain a performance edge. But for those athletes who do, the health consequences could be disastrous. PMID- 27414229 TI - Exercise adviser. PMID- 27414231 TI - Matrix Metalloproteinases and Their Tissue Inhibitors in Comparison to Other Inflammatory Proteins in Gastric Cancer (GC). AB - Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. The lack of management strategies for the diagnosis of GC in patients gives rise to the challenging questions about the new tumor markers for GC. Developing malignant process may induce local and systemic inflammatory responses. Cancer associated inflammation is characterized by the infiltration of immune cells. Thus, the inflammation-related proteins, such as cytokines, chemokines, and selected matrix metalloproteinases, may facilitate the growth, proliferation, and migration of tumor cells, including GC. Based on our previous findings, we assessed the significance of various inflammatory mediators as candidates for tumor markers of GC. PMID- 27414232 TI - Synthesis of 5-Amino-2,5-dihydro-1H-benzo[b]azepines Using a One-Pot Multibond Forming Process. AB - Rapid access to allylic trichloroacetimidates bearing a 2-allylaminoaryl group from readily available 2-iodoanilines combined with a one-pot multibond forming process has allowed the efficient synthesis of a series of 5-amino-2,5-dihydro-1H benzo[b]azepines. The potential of these compounds as synthetic building blocks was demonstrated by the preparation of a late-stage intermediate of the hyponatremia agent, mozavaptan. PMID- 27414233 TI - Characteristics of Congenital Coronary Artery Fistulas Complicated with Infective Endocarditis: Analysis of 25 Reported Cases. AB - Congenital coronary artery fistulas (CAFs) are infrequent congenital coronary artery anomalies. Complications such as left-to-right shunt, congestive heart failure, myocardial infarction, pericardial effusion, aneurysm formation, rupture, hemopericardium, pulmonary hypertension, infective endocarditis (IE), syncope, stroke, and sudden death may occur with a variable low frequency. To describe the clinical characteristics of patients with CAFs complicated by IE. A search was conducted through PubMed using the terms "CAFs" and "IE." Papers with a full description of the fistula characteristics and detailed data regarding bacterial endocarditis were included for evaluation. In the overall group of reviewed subjects (n = 25, 9 females), the mean patient age was 42.5 years (range: 16 and 87). The right coronary artery (RCA) and left coronary artery (LCA) contributed equally to fistula formation. Terminations into the right heart side occurred in 19 (76%) fistulas. The majority of the fistulas (92%) were unilateral. The cultured microorganism was Streptococcus in 14 (56%) and Staphylococcus in 4 (16%) of the reviewed subjects. Echocardiographic single or multiple valvular regurgitation was found in 8 (32%) of the reviewed subjects. Small and large intracardiac vegetations were detected in 18 patients (72%). Antibiotic therapy was initiated in 20 (80%) subjects and 16 fistulas were treated surgically. During surgery, spontaneous closure of the fistula was observed in one patient. Percutaneous therapeutic embolization (PTE) was successfully performed in two subjects. CAFs complicated by IE may affect all age groups with a slight male preponderance. Unilateral fistulas, either arising from the right or left coronary artery, are predominant, draining mainly into the right heart side. It is emphasized that antibiotic prophylaxis is strongly advised for pediatric and adult patients with congenital CAFs. PMID- 27414234 TI - The compassionate sexist? How benevolent sexism promotes and undermines gender equality in the workplace. AB - Although sexist attitudes are generally thought to undermine support for employment equity (EE) policies supporting women, we argue that the effects of benevolent sexism are more complex. Across 4 studies, we extend the ambivalent sexism literature by examining both the positive and the negative effects benevolent sexism has for the support of gender-based EE policies. On the positive side, we show that individuals who endorse benevolent sexist attitudes on trait measures of sexism (Study 1) and individuals primed with benevolent sexist attitudes (Study 2) are more likely to support an EE policy, and that this effect is mediated by feelings of compassion. On the negative side, we find that this support extends only to EE policies that promote the hiring of women in feminine, and not in masculine, positions (Study 3 and 4). Thus, while benevolent sexism may appear to promote gender equality, it subtly undermines it by contributing to occupational gender segregation and leading to inaction in promoting women in positions in which they are underrepresented (i.e., masculine positions). (PsycINFO Database Record PMID- 27414235 TI - Knowledge of identity and reputation: Do people have knowledge of others' perceptions? AB - It may be important to know when our impressions of someone differ from how that person sees him/herself and how others see that same person. We investigated whether people are aware of how their friends see themselves (knowledge of identity) and are seen by others (knowledge of reputation). Previous research indicates that, for physical attractiveness, romantic partners do have such knowledge of others' perceptions, but it is unknown whether people in platonic relationships also detect such discrepancies between their own perceptions and others'. We examined this phenomenon for a new set of characteristics: the Big Five personality traits. Our primary research questions pertained to identity accuracy and reputation accuracy (i.e., knowledge of a target's self-views and how others view the target, respectively) and identity insight and reputation insight (i.e., identity accuracy and reputation accuracy that cannot be accounted for by a potential artifact: perceivers assuming that others share their own views of targets). However, after a series of preliminary tests, we did not examine reputation insight, as several necessary conditions were not met, indicating that any effects would likely be spurious. We did find that perceivers can accurately infer a target's identity and reputation on global personality traits (identity and reputation accuracy), and that perceivers can sometimes accurately distinguish between their own perceptions of targets and targets' self views, but not others' views of targets (i.e., identity, but not reputation, insight). Finally, we explored boundary conditions for knowledge of others' perceptions and whether knowledge of identity is correlated with knowledge of reputation. (PsycINFO Database Record PMID- 27414236 TI - Paying for performance: Performance incentives increase desire for the reward object. AB - The current research examines how exposure to performance incentives affects one's desire for the reward object. We hypothesized that the flexible nature of performance incentives creates an attentional fixation on the reward object (e.g., money), which leads people to become more desirous of the rewards. Results from 5 laboratory experiments and 1 large-scale field study provide support for this prediction. When performance was incentivized with monetary rewards, participants reported being more desirous of money (Study 1), put in more effort to earn additional money in an ensuing task (Study 2), and were less willing to donate money to charity (Study 4). We replicated the result with nonmonetary rewards (Study 5). We also found that performance incentives increased attention to the reward object during the task, which in part explains the observed effects (Study 6). A large-scale field study replicated these findings in a real-world setting (Study 7). One laboratory experiment failed to replicate (Study 3). (PsycINFO Database Record PMID- 27414237 TI - Persistent high temperature and low precipitation reduce peat carbon accumulation. PMID- 27414238 TI - How shortcomings in the mental health system affect the use of involuntary community treatment orders. AB - Objective The aim of the present study was to examine stakeholder perspectives on how the operation of the mental health system affects the use of involuntary community treatment orders (CTOs). Methods A qualitative study was performed, consisting of semi-structured interviews about CTO experiences with 38 purposively selected participants in New South Wales (NSW), Australia. Participants included mental health consumers (n=5), carers (n=6), clinicians (n=15) and members of the Mental Health Review Tribunal of NSW (n=12). Data were analysed using established qualitative methodologies. Results Analysis of participant accounts about CTOs and their role within the mental health system identified two key themes, namely that: (1) CTOs are used to increase access to services; and (2) CTOs cannot remedy non-existent or inadequate services. Conclusion The findings of the present study indicate that deficiencies in health service structures and resourcing are a significant factor in CTO use. This raises questions about policy accountability for mental health services (both voluntary and involuntary), as well as about the usefulness of CTOs, justifications for CTO use and the legal criteria regulating CTO implementation. What is known about this topic? Following the deinstitutionalisation of psychiatric services over recent decades, community settings are increasingly the focus for the delivery of mental health services to people living with severe and persistent mental illnesses. The rates of use of involuntary treatment in Australian community settings (under CTOs) vary between state and territory jurisdictions and are high by world standards; however, the reasons for variation in rates of CTO use are not well understood. What does this paper add? This paper provides an empirical basis for a link between the politics of mental health and the uptake and usefulness of CTOs. What are the implications for practitioners? This paper makes explicit the real-world demands on the mental health system and how service deficiencies are a significant determinant in the use of CTOs. Practitioners and policy makers need to be candid about system limitations and how they factor in clinical and legal justifications for using involuntary treatment. The results of the present study provide data to support advocacy to improve policy accountability and resourcing of community mental health services. PMID- 27414239 TI - Men cite themselves more than women do. PMID- 27414240 TI - Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior? AB - Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27414241 TI - Dicarboxylic acids, omega-oxocarboxylic acids, alpha-dicarbonyls, WSOC, OC, EC, and inorganic ions in wintertime size-segregated aerosols from central India: Sources and formation processes. AB - The size distributions of aerosols can provide evidences for their sources and formation processes in the atmosphere. Size-segregated aerosols (9-sizes) were collected in urban site (Raipur: 21.2 degrees N and 82.3 degrees E) in central India during winter of 2012-2013. The samples were analyzed for dicarboxylic acids (C2-C12), omega-oxocarboxylic acids (omegaC2-omegaC9), pyruvic acid and alpha-dicarbonyls (C2-C3) as well as elemental carbon (EC), organic carbon (OC), water-soluble OC (WSOC) and inorganic ions. Diacids showed a predominance of oxalic acid (C2) followed by succinic and azelaic acid whereas omega-oxoacids exhibited a predominance of glyoxylic acid and glyoxal was more abundant than methylglyoxal in all the sizes. Diacids, omega-oxoacids and alpha-dicarbonyls showed bimodal size distribution with peaks in fine and coarse modes. High correlations of fine mode diacids and related compounds with potassium and levoglucosan suggest that they were presumably due to a substantial contribution of primary emission from biomass burning and secondary production from biomass burning derived precursors. High correlations of C2 with higher carbon number diacids (C3-C9) suggest that they have similar sources and C2 may be produced via the decay of its higher homologous diacids in fine mode. Considerable portions of diacids and related compounds in coarse mode suggest that they were associated with mineral dust particles by their adsorption and photooxidation of anthropogenic and biogenic precursors via heterogeneous reaction on dust surface. This study demonstrates that biomass burning and dust particles are two major factors to control the size distribution of diacids and related compounds in the urban aerosols from central India. PMID- 27414243 TI - [Update Minimally Invasive Lamellar Keratoplasty: DMEK, DSAEK and DALK]. AB - BACKGROUND: The spectrum of operative interventions in corneal disorders requiring keratoplasty has been expanded considerably in recent years. In addition to the standard technique with full-thickness replacement of the cornea (perforating keratoplasty), lamellar techniques have been introduced. The aim of this review is to highlight current opportunities, indications and complications, as well as possible strategies to standardise lamellar keratoplasties. MATERIALS AND METHODS: Our own data and a review of the literature in PubMed are summarised. RESULTS: Performing "Descemet Membrane Endothelial Keratoplasty" (DMEK), "Descemt Stripping Automated Endothelial Keratoplasty" (DSAEK) and "Deep Anterior Lamellar Keratoplasty" (DALK) can provide patients with disorders of the corneal endothelium or the anterior corneal stroma with minimally invasive corneal grafts at a reduced risk of complications. CONCLUSION: DMEK and DSAEK are now internationally the surgical methods of choice in patients with endothelial corneal pathologies, i.e. in Fuchs' Endothelial Dystrophy. The DALK technique for lamellar replacement of the anterior stroma, i.e. in keratoconus, needs further standardisation, so that DALK can in future be performed more often even in less specialised departments. Major advantages of lamellar keratoplasties are the very good results in visual outcome and fewer immune reactions or graft rejections. Even intraoperative complications are rare. In the long term, further strategies are desirable for the standardisation of lamellar keratoplasties and its establishment as the primary standard procedure. PMID- 27414242 TI - Validation of list equivalency for Mandarin speech materials to use with cochlear implant listeners. AB - OBJECTIVES: Speech materials validated with normal-hearing listeners may not be appropriate for clinical assessment of cochlear implant (CI) users. The aim of this study was to validate list equivalency of the Mandarin Speech Perception (MSP) sentences, disyllables, and monosyllables in Mandarin-speaking CI patients. DESIGN: Recognition of MSP sentences, disyllables, and monosyllables each were measured for all 10 lists. STUDY SAMPLE: 67 adult and 32 pediatric Mandarin speaking CI users. RESULTS: There was no significant difference between adult and pediatric subject groups for all test materials. Significant differences were observed among lists within each test. After removing one or two lists within each test, no significant differences were observed among the remaining lists. While there was equal variance among lists within a given test, the variance was larger for children than for adults, and increased from monosyllables to disyllables to sentences. CONCLUSIONS: Some adjustment to test lists previously validated with CI simulations was needed to create perceptually equivalent lists for real CI users, suggesting that test materials should be validated in the targeted population. Differences in mean scores and variance across test materials suggest that CI users may differ in their ability to make use of contextual cues available in sentences and disyllables. PMID- 27414244 TI - A conveniently prepared and hypersensitized small molecular fluorescent probe: Rapidly detecting free zinc ion in HepG2 cells and Arabidopsis. AB - In this paper, we reported a conveniently prepared fluorescent probe for zinc ions detection, which constructed by the condensation reaction between p (benzothiazolyl)aniline with 4, 4- diethylaminesalicylaldehyde. The sensing ability of the probe toward zinc ions in vitro was tested by a series of UV-Vis and fluorescence spectroscopy studies, which showed that the probe possessed high sensitivity with a detection limit of 5.8nM and a rapid response time of 10s. We also carried out fluorescent bio-imaging of the probe for zinc ions in human liver hepatocellular carcinoma cells (HepG2), which showed that the probe could be utilized to detect the intracellular endogenous zinc ions visually without introducing external zinc sources. Meanwhile, co-staining experiment with organelle selective trackers was performed to illustrate that the probe could locate at endoplasmic reticulum. Finally, we successfully used it as a zinc ion developer in plant tissue, which clearly demonstrated the distribution of zinc ions in the growth stage of plant tissue. PMID- 27414245 TI - Sensitive detection of multiple pathogens using a single DNA probe. AB - A simple but promising electrochemical DNA nanosensor was designed, constructed and applied to differentiate a few food-borne pathogens. The DNA probe was initially designed to have a complementary region in Vibrio parahaemolyticus (VP) genome and to make different hybridization patterns with other selected pathogens. The sensor was based on a screen printed carbon electrode (SPCE) modified with polylactide-stabilized gold nanoparticles (PLA-AuNPs) and methylene blue (MB) was employed as the redox indicator binding better to single-stranded DNA. The immobilization and hybridization events were assessed using differential pulse voltammetry (DPV). The fabricated biosensor was able to specifically distinguish complementary, non-complementary and mismatched oligonucleotides. DNA was measured in the range of 2.0*10(-9)-2.0*10(-13)M with a detection limit of 5.3*10(-12)M. The relative standard deviation for 6 replications of DPV measurement of 0.2uM complementary DNA was 4.88%. The fabricated DNA biosensor was considered stable and portable as indicated by a recovery of more than 80% after a storage period of 6 months at 4-45 degrees C. Cross-reactivity studies against various food-borne pathogens showed a reliably sensitive detection of VP. PMID- 27414246 TI - Nano optical sensor binuclear Pt-2-pyrazinecarboxylic acid -bipyridine for enhancement of the efficiency of 3-nitrotyrosine biomarker for early diagnosis of liver cirrhosis with minimal hepatic encephalopathy. AB - A new, precise, and very selective method for increasing the impact and assessment of 3-nitrotyrosine (3-Nty) as a biomarker for early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) disease was developed. The method depends on the formation of the ion pair associate between 3-nitrotyrosine and the optical sensor binuclear Pt-2-pyrazinecarboxylic acid (pca)-Bipyridine (bpy) complex doped in sol-gel matrix in buffer solution of pH 7.3. The binuclear Pt (pca)(bpy) has +II net charge which is very selective and sensitive for [3 Nty](-2) at pH 7.3 in serum sample of liver cirrhosis with MHE diseases. 3 nitrotyrosine (3-Nty) quenches the luminescence intensity of the nano optical sensor binuclear Pt(pca) (bpy) at 528nm after excitation at 370nm, pH 7.3. The remarkable quenching of the luminescence intensity at 528nm of nano binuclear Pt(pca) (bpy) doped in sol-gel matrix by various concentrations of the 3-Nty was successfully used as an optical sensor for the assessment of 3-Nty in different serum samples of (MHE) in patients with liver cirrhosis. The calibration plot was achieved over the concentration range 1.85*10(-5) - 7.95*10(-10)molL(-1) 3-Nty with a correlation coefficient of (0.999) and a detection limit of (4.7*10( 10)molL(-1)). The method increases the sensitivity (93.75%) and specificity (96.45%) of 3-Nty as a biomarker for early diagnosis of liver cirrhosis with MHE in patients. PMID- 27414248 TI - Potential therapeutic action of natural products from traditional Chinese medicine on Alzheimer's disease animal models targeting neurotrophic factors. AB - Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells leads to memory loss and cognitive decline. To reduce the death rate and improve the biological activity of neurocytes, neurotrophic factors (NTFs) exhibit therapeutic effect on AD. However, therapeutic application of exogenous NTFs in treatment of AD is largely limited due to short half-life, poor stability, etc. Various extracts of traditional Chinese medicine (TCM) have been shown to exhibit therapeutic effects on AD, and some of these effects are associated with regulation on the expression of nerve growth factor, brain derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) and their associated receptors. This article reviews the progress on promotion of Panax ginseng, Rehmannia glutinosa Libosch., Epimedium, Polygala tenuifolia Willd, and seven other TCMs on secretion of NTFs during AD, with a view to preparation development and clinical application of these TCMs on AD. PMID- 27414249 TI - Dynamics of a microorganism in a sheared viscoelastic liquid. AB - In this paper, we investigate the dynamics of a model spherical microorganism, called squirmer, suspended in a viscoelastic fluid undergoing unconfined shear flow. The effect of the interplay of shear flow, fluid viscoelasticity, and self propulsion on the orientational dynamics is addressed. In the limit of weak viscoelasticity, quantified by the Deborah number, an analytical expression for the squirmer angular velocity is derived by means of the generalized reciprocity theorem. Direct finite element simulations are carried out to study the squirmer dynamics at larger Deborah numbers. Our results show that the orientational dynamics of active microorganisms in a sheared viscoelastic fluid greatly differs from that observed in Newtonian suspensions. Fluid viscoelasticity leads to a drift of the particle orientation vector towards the vorticity axis or the flow gradient plane depending on the Deborah number, the relative weight between the self-propulsion velocity and the flow characteristic velocity, and the type of swimming. Generally, pullers and pushers show an opposite equilibrium orientation. The results reported in the present paper could be helpful in designing devices where separation of microorganisms, based on their self propulsion mechanism, is obtained. PMID- 27414247 TI - The role of HDL in plaque stabilization and regression: basic mechanisms and clinical implications. AB - On the basis of studies that extend back to the early 1900s, regression and stabilization of atherosclerosis in humans has progressed from being a concept to one that is achievable. Successful attempts at regression generally applied robust measures to improve plasma lipoprotein profiles. Possible mechanisms responsible for lesion shrinkage include decreased retention of atherogenic apolipoprotein B within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of lesional foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris as well as other components of the plaque. Currently available clinical agents, however, still fail to stop most cardiovascular events. For years, HDL has been considered the 'good cholesterol.' Clinical intervention studies to causally link plasma HDL-C levels to decreased progression or to the regression of atherosclerotic plaques are relatively few because of the lack of therapeutic agents that can selectively and potently increase HDL-C. The negative results of studies that were carried out have led to uncertainty as to the role that HDL plays in atherosclerosis. It is becoming clearer, however, that HDL function rather than quantity is most crucial and, therefore, discovery of agents that enhance the quality of HDL should be the goal. PMID- 27414251 TI - Effect of plant resistance and BioAct WG (Purpureocillium lilacinum strain 251) on Meloidogyne incognita in a tomato-cucumber rotation in a greenhouse. AB - BACKGROUND: The effectiveness of combining resistant tomato with BioAct WG (Purpureocillium lilacinum strain 251, Pl251) against Meloidogyne incognita was assessed in a tomato-cucumber rotation in a greenhouse over 2 years. Additionally, the enzymatic activity of the fungus, the percentage of fungal egg and juvenile parasitism, cardinal temperatures and the effect of water potential on mycelial growth and the soil receptivity to Pl251 were determined in vitro. RESULTS: Plant resistance was the only factor that suppressed nematode and crop yield losses. Percentage of egg parasitism in plots treated with BioAct WG was less than 2.6%. However, under in vitro conditions, Pl251 showed protease, lipase and chitinase activities and parasitised 94.5% of eggs, but no juveniles. Cardinal temperatures were 14.2, 24-26 and 35.4 degrees C. The maximum Pl251 mycelial growth was at -0.25 MPa and 25 degrees C. Soil temperatures and water potential in the greenhouse were in the range of the fungus. However, soil receptivity was lower in greenhouse soil, irrespective of sterilisation, than in sterilised sand. CONCLUSION: Plant resistance was the only factor able to suppress nematode densities, disease severity and yield losses, and to protect the following cucumber crop. Environmental factors involved in soil receptivity could have negatively affected fungus effectiveness. (c) 2016 Society of Chemical Industry. PMID- 27414252 TI - Polydimethysiloxane Modified Silica Nanochannel Membrane for Hydrophobicity-Based Molecular Filtration and Detection. AB - We report in this work the fabrication of ultrathin silica nanochannel membranes inhomogeneously modified by polydimethysiloxane (PDMS), designated as PDMS-SNM, for hydrophobicity-based molecular filtration and detection. The modification was accomplished by spatially selective evaporation of hydrophobic PDMS oligomers onto the top surface of the membrane and orifice of silica nanochannels. Thanks to this hydrophobic ultrathin layer and beneath ultrasmall channels (2-3 nm in diameter), only small hydrophobic molecules are able to transport through the PDMS-SNM, whereas hydrophilic and large ones are remarkably inhibited. We first employed this PDMS-SNM as the molecular sieving matrix for selective electrochemical detection of hydrophobic organophosphates (OPs) in milk samples without pretreatment. The PDMS-SNM modified electrode displayed an excellent analytical performance and antifouling/anti-interference ability. We also prepared the free-standing PDMS-SNM consisting of perforated channels, which could filtrate molecules based on their hydrophobicity with an excellent selectivity. As demonstrated, 2,4,6-trinitrotoluene and dopamine could be separated with a selectivity coefficient as high as 335. Moreover, because of the inhomogeneous nanochannel structure and ultrasmall thickness, a remarkably high flux of hydrophobic molecules across the PDMS-SNM was obtained, which was 3-4 orders of magnitude higher than that reported previously. PMID- 27414250 TI - Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells. AB - The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. Our data suggest that incorporation of physiological amounts of MCM5 promotes aberrant reverse transcription, leading to partial incapacitation of cDNA, whereas increased MCM5 abundance leads to reduced reverse transcription and infection. Therefore, MCM5 has the properties of an inhibitory factor that interferes with production of an integration-competent cDNA product. PMID- 27414253 TI - Transforming growth factor-beta activated long non-coding RNA ATB plays an important role in acute rejection of renal allografts and may impacts the postoperative pharmaceutical immunosuppression therapy. AB - AIM: Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. The lncRNA activated by transforming growth factor beta (TGF-beta) (lncRNA-ATB) was discovered as a prognostic factor in hepatocellular carcinoma, gastric cancer, and colorectal cancer. However, little is known about the role of lncRNA-ATB in renal transplantation. This study aimed to assess lncRNA-ATB expression in renal transplant patients with acute kidney injury and explore its role in postoperative pharmaceutical immunosuppression therapy. METHODS: We detected lncRNA-ATB expression in the kidney biopsies of a cohort of 72 patients with renal allograft rejection and 36 control transplant patients. lncRNA-ATB were overexpressed from lentiviral vectors in renal cells. RESULTS: We found that lncRNA-ATB was remarkably upregulated in patients with acute rejection compared with controls. Meanwhile, lncRNA-ATB could influence the kidney cell phenotypes and impact the nephrotoxicity of immunosuppressive drug. CONCLUSION: In conclusion, lncRNA-ATB are strongly altered in patients with acute rejection and may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function. PMID- 27414255 TI - Renal Clearable Organic Nanocarriers for Bioimaging and Drug Delivery. AB - Renally cleared zwitterionic nanocarriers (H-Dots) are composed of epsilon polylysine backbone for charge variations, near-infrared fluorophores for bioimaging, and beta-cyclodextrins for potential drug delivery. H-Dots show ideal systemic circulation and rapid distribution and excrete from normal tissue/organ via renal excretion after complete targeting to the tumor site without nonspecific uptake by the immune system. PMID- 27414256 TI - Comparison of chelates for enhancing Ricinus communis L. phytoremediation of Cd and Pb contaminated soil. AB - We studied chelate effects on castor bean (Ricinus communis L.) growth. These effects included Cd and Pb accumulation in plant tissues and the chemical behavior of Cd and Pb in the plant rhizosphere and non-rhizosphere. Tests were conducted in a glasshouse using the rhizobag method. Two castor bean cultivars (Zibo-3 and Zibo-9) were grown in soil contaminated with 3.53mg/kg Cd and 274mg/kg Pb. The soil was treated with citric acid (CA), ethylenediamine disuccinic acid (EDDS) or ethylenediamine tetraacetic acid (EDTA) (5mmol/kg). EDDS-treated soil produced 28.8% and 59.4% greater biomass for Zibo-3 and Zibo-9 respectively. In contrast, CA and EDTA inhibited the growth of the two cultivars. Zibo-9 had greater tolerance than Zibo-3 to chelate toxicity. Based on Cd and Pb plant uptake, EDDS could substitute for EDTA for phytoremediation of Cd in soil. EDTA was the most effective of the three chelates for Pb phytoremediation but it is less suitable for field use due to toxicology environmental persistence. Acid extractable Cd and Pb in the rhizosphere or reducible Cd and Pb in the non rhizosphere of soil were the main influences on Cd and Pb accumulation in castor bean. PMID- 27414257 TI - Organochlorine contaminants in the muscle, liver and brain of seabirds (Larus) from the coastal area of the Southern Baltic. AB - The presence of persistent organic pollutants in the environment manifests itself most strongly in the marine trophic chain, where the highest link is comprised of seabirds. At the same time, seabirds are excellent indicators of contamination in their habitat. The present study concentrates on toxic substances: polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated organic pesticides (OCPs) accumulated in the livers, pectoral muscles and brains of dead gulls collected along the Polish coast of the Baltic Sea in the years 2010-12. The highest toxic equivalence was determined in the livers of Larus argentatus (TEQ(birds TEF)-28.3pgg(-1) ww) and Larus marinus (TEQ(birds TEF)-29.9pgg(-1) ww.). However, the toxic equivalence of muscles was lower and amounted to 3.9pgg(-1) ww. and 7.8pgg(-1) ww. respectively for the two species. The lowest toxic equivalence was found in the brains of birds, where only one, the most toxic, 2,3,7,8 TCDD congener was found (TEQ(birds TEF) 0.87pgg(-1) ww). The highest concentration of chloroorganic pesticides was determined in the brains of the birds (total OCP 167.8pgg(-1) ww.), lower concentrations were found in the livers (total OCP 92.1pgg(-1) ww.) and muscles (total OCP 43.1pgg(-1) ww.). With regard to pesticides, the highest proportion in the total OCP content was constituted by DDT and its isomers (liver 81%, muscles 77% and brain 55%). High concentrations of the studied pollutants in the livers of gulls found dead on the coast of the Southern Baltic could have been effected by levels of contamination in the birds' last meals, which resulted in a seven fold increase of the liver's toxic equivalence and a two-fold increase in OCP concentration in relation to muscles. PMID- 27414260 TI - Macroscopic Responsive Liquid Quantum Dots Constructed via Pillar[5]arene-Based Host-Guest Interactions. AB - Liquid quantum dots (QDs) have been used as a fluorescent films sensor. Constructing a macroscopic, responsive, liquid QD system for lysine (Lys) is a challenging task. To achieve a selective macroscopic response towards Lys, herein we present a new strategy for integrating host-guest chemistry into a liquid QD system. Water-soluble pillar[5]arene WP5 was designed and synthesized as a host. WP5 was introduced onto the surface of PEG1810-modified QDs by host-guest interactions to obtain liquid WP5-1810-QDs. The interaction between WP5 and Lys is stronger than that between WP5 and PEG-1810, causing WP5 to be released from the 1810-QDs surface in the presence of Lys, resulting in macroscopic fluorescence quenching. This smart material shows promise in amino acid sensing and separation. PMID- 27414258 TI - Multibiomarker response in ten spotted live-bearer fish Cnesterodon decemmaculatus (Jenyns, 1842) exposed to Reconquista river water. AB - The aim of this paper is to assess the water quality to chemical pollution at Roggero Dam, the headwater of the Reconquista river, and to perform a Cadmium (Cd) contamination pulse simulation through a wide battery of biomarkers which included: genotoxicity and enzymatic biomarker parameters on a neotropical teleost fish namely Cnesterodon decemmaculatus. Water samples were taken in order to determine the river's physicochemical profile. An integrative approach was applied using a biomarker index. The bioassay involved the use of laboratory culture adult animals, acclimatized in moderately hard water (MHW) and fed ad libitum. A semi-static 96h bioassay was conducted and the experimental groups were as follows: [1] river water (Rg); [2] river water + 2mg/L Cd (RgCd); [3] MHW + 2mg/L Cadmium (Cd), positive metal control; [4] MHW + 5mg/L Cyclophosphamide (positive genotoxicity control -CP); [5] MWH, negative control (NC). At the end of the exposure time fishes were sectioned and the following biomarkers were determined: 1) condition factor rate (CF); 2) for the anterior section (A) (head): glutathione (GSH) and protein (Pr) content; 3) for the body midsection (M) (viscera): Pr, GSH, Glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD). Blood samples were also taken from the fish specimens to estimate the frequency of micronuclei (MN) as well as other nuclear abnormalities (NA). The physicochemical profile of the river water sample indicated high Copper concentrations. CAT and SOD activity and total Pr content did not show any significant changes. GST activity decreased in fish exposed to Rg, while GSH content decreased significantly for all treatments compared to controls in MHW. These results would seem to point to a reduction in cell defense capability as a result of the depletion antioxidants such as GSH. The NA frequency increased significantly in all treated groups while MN frequency was increased only in Cd and CP groups. Using some the biomarkers measured, a biomarker index was estimated which revealed that fish exposed to Rg were 90% affected or highly affected, while those exposed to RgCd were 80% and Cd 68% affected or highly affected. The obtained results indicate the usefulness of the use of a battery of variables by means of the biomarker index to analyze water quality. PMID- 27414261 TI - Rapid, accurate, and comparative differentiation of clinically and industrially relevant microorganisms via multiple vibrational spectroscopic fingerprinting. AB - Despite the fact that various microorganisms (e.g., bacteria, fungi, viruses, etc.) have been linked with infectious diseases, their crucial role towards sustaining life on Earth is undeniable. The huge biodiversity, combined with the wide range of biochemical capabilities of these organisms, have always been the driving force behind their large number of current, and, as of yet, undiscovered future applications. The presence of such diversity could be said to expedite the need for the development of rapid, accurate and sensitive techniques which allow for the detection, differentiation, identification and classification of such organisms. In this study, we employed Fourier transform infrared (FT-IR), Raman, and surface enhanced Raman scattering (SERS) spectroscopies, as molecular whole organism fingerprinting techniques, combined with multivariate statistical analysis approaches for the classification of a range of industrial, environmental or clinically relevant bacteria (P. aeruginosa, P. putida, E. coli, E. faecium, S. lividans, B. subtilis, B. cereus) and yeast (S. cerevisiae). Principal components-discriminant function analysis (PC-DFA) scores plots of the spectral data collected from all three techniques allowed for the clear differentiation of all the samples down to sub-species level. The partial least squares-discriminant analysis (PLS-DA) models generated using the SERS spectral data displayed lower accuracy (74.9%) when compared to those obtained from conventional Raman (97.8%) and FT-IR (96.2%) analyses. In addition, whilst background fluorescence was detected in Raman spectra for S. cerevisiae, this fluorescence was quenched when applying SERS to the same species, and conversely SERS appeared to introduce strong fluorescence when analysing P. putida. It is also worth noting that FT-IR analysis provided spectral data of high quality and reproducibility for the whole sample set, suggesting its applicability to a wider range of samples, and perhaps the most suitable for the analysis of mixed cultures in future studies. Furthermore, our results suggest that while each of these spectroscopic approaches may favour different organisms (sample types), when combined, they would provide complementary and more in-depth knowledge (structural and/or metabolic state) of biological systems. To the best of our knowledge, this is the first time that such a comparative and combined spectroscopic study (using FT-IR, Raman and SERS) has been carried out on microbial samples. PMID- 27414259 TI - The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non obese diabetic mice autoimmune hepatitis mouse model. AB - Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA) DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs ), which had decreased programmed death (PD)-1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID- 27414262 TI - Histologic transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma. AB - Although generally considered a clinically indolent neoplasm, CLL/SLL may undergo transformation to a clinically aggressive lymphoma. The most common form of transformation, to DLBCL, is also known as Richter syndrome. Transformation determines the course of the disease and is associated with unfavorable patient outcome. Precise detection of transformation and identification of predictive biomarkers and specific molecular pathways implicated in the pathobiology of transformation in CLL/SLL will enable personalized therapeutic approach and provide potential avenues for improving the clinical outcome of patients. In this review, we present an overview of the pathologic features, risk factors, and pathogenic mechanisms of CLL/SLL transformation. Am. J. Hematol. 91:1036-1043, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27414265 TI - Recent Developments in Fully Fluctuating Field-Theoretic Simulations of Polymer Melts and Solutions. AB - We review the latest developments in computational methods for direct simulation of fully fluctuating field theories of polymeric assemblies. In this context, we describe a newly developed theoretical and computational framework for accurately computing fluctuation-corrected phase diagrams of mesostructured polymer systems and report the first such complete phase diagram for a diblock copolymer melt. The method is based on complex Langevin sampling of a UV regularized field theoretic model, with Helmholtz free energies computed using thermodynamic integration. UV regularization ensures that the free energies do not have an arbitrary reference; they can be compared between incommensurate phases, permitting for the first time the computation of order-order transitions with fluctuation corrections. We further demonstrate that computed free energies are accurate in the disordered phase by comparison to perturbation theory on the one loop level. Importantly, we note that our method uses no uncontrolled approximations beyond the initial definition of a coarse-grained molecular model for the polymer melt or solution. The method can be applied straightforwardly to melts and solutions containing multiple species with diverse polymer architectures. PMID- 27414263 TI - Updates to the zoonotic niche map of Ebola virus disease in Africa. AB - As the outbreak of Ebola virus disease (EVD) in West Africa is now contained, attention is turning from control to future outbreak prediction and prevention. Building on a previously published zoonotic niche map (Pigott et al., 2014), this study incorporates new human and animal occurrence data and expands upon the way in which potential bat EVD reservoir species are incorporated. This update demonstrates the potential for incorporating and updating data used to generate the predicted suitability map. A new data portal for sharing such maps is discussed. This output represents the most up-to-date estimate of the extent of EVD zoonotic risk in Africa. These maps can assist in strengthening surveillance and response capacity to contain viral haemorrhagic fevers. PMID- 27414267 TI - Counterpoint, patronage and professionalism. PMID- 27414266 TI - QuickStats: Percentage* of Adults Aged >=18 Years with Two or More Visits to an Emergency Department? in the Previous 12 Months, by Home OwnershipS and Age Group - National Health Interview Survey, United States, 2015. PMID- 27414264 TI - Structural Polymorphism of Alzheimer's beta-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study. AB - The amyloid-beta (Abeta) peptide of Alzheimer's disease (AD) forms polymorphic fibrils on the micrometer and molecular scales. Various fibril growth conditions have been identified to cause polymorphism, but the intrinsic amino acid sequence basis for this polymorphism has been unclear. Several single-site mutations in the center of the Abeta sequence cause different disease phenotypes and fibrillization properties. The E22G (Arctic) mutant is found in familial AD and forms protofibrils more rapidly than wild-type Abeta. Here, we use solid-state NMR spectroscopy to investigate the structure, dynamics, hydration and morphology of Arctic E22G Abeta40 fibrils. (13)C, (15)N-labeled synthetic E22G Abeta40 peptides are studied and compared with wild-type and Osaka E22Delta Abeta40 fibrils. Under the same fibrillization conditions, Arctic Abeta40 exhibits a high degree of polymorphism, showing at least four sets of NMR chemical shifts for various residues, while the Osaka and wild-type Abeta40 fibrils show a single or a predominant set of chemical shifts. Thus, structural polymorphism is intrinsic to the Arctic E22G Abeta40 sequence. Chemical shifts and inter-residue contacts obtained from 2D correlation spectra indicate that one of the major Arctic conformers has surprisingly high structural similarity with wild-type Abeta42. (13)C-(1)H dipolar order parameters, (1)H rotating-frame spin-lattice relaxation times and water-to-protein spin diffusion experiments reveal substantial differences in the dynamics and hydration of Arctic, Osaka and wild-type Abeta40 fibrils. Together, these results strongly suggest that electrostatic interactions in the center of the Abeta peptide sequence play a crucial role in the three dimensional fold of the fibrils, and by inference, fibril-induced neuronal toxicity and AD pathogenesis. PMID- 27414268 TI - Sleepy radicals. PMID- 27414269 TI - Notice: new contact numbers for London editorial office. PMID- 27414270 TI - Experimental approaches to free radicals and ageing. PMID- 27414272 TI - Is free radical generation an important component of ischemia/reperfusion injury? Part 1. PMID- 27414271 TI - Low density lipoproteins and atherosclerosis-quantity or quality? AB - Oxidative modification of low density lipoprotein (LDL) appears to be important in the pathogenesis of atherosclerosis. Inhibiting the oxidation of LDL may retard or prevent the atherogenic process. However, susceptibility of LDL to oxidation in vitro and its atherogenicity in vivo may not always correlate. Subjects with familial hypercholesterolaemia (FH) develop severe, premature atherosclerosis despite having large, bouyant LDL particles which are less susceptible to oxidation. High dose, long-term vitamin E increases the resistance of LDL to oxidation but, unlike probucol, has no effect on xanthoma regression in homozygous FH. In FH, the quantity of LDL takes priority and the main aim of therapy is reduction of LDL bulk. Individuals with small, dense LDL particles are at increased risk for atherosclerosis despite desirable plasma LDL cholesterol levels. Small, dense LDL particles are more susceptible to oxidation and in these subjects antioxidant therapy may be of greater benefit. In subjects with atherosclerosis, current management should be aimed primarily at reducing the LDL cholesterol level. In the future antioxidant therapy may complement our management of hypercholesterolaemia. PMID- 27414273 TI - Is free radical generation an important component of ischemia/reperfusion injury? Part 2. PMID- 27414274 TI - Quantification of Mn-SOD mRNAs by using a competitive reverse-transcription polymerase chain reaction. AB - The manganese superoxide dismutase plays an important role in the cellular response to oxidative stress and appears to be highly regulated by many factors. The study of this gene's expression is difficult to achieve due to multiple rat Mn-SOD transcripts. In this report we described the quantification of the rat Mn SOD transcripts by competitive reverse transcription-polymerase chain reaction. The competitor RNA was transcribed from a synthetic gene generated by PCR. This gene was composed of the T7 polymerase promoter linked to a 102 base-pairs deleted rat Mn-SOD cDNA. Both the target RNA and the competitor RNA were reverse transcribed and coamplified with the same primers. All the rat Mn-SOD mRNAs were simultaneously quantified by amplification of a common region. The use of a fluorescent primer led to fluorescent PCR products detected and quantified by the use of an automated DNA sequencer which avoides the use of the radioactivity. Small variations in Mn-SOD mRNA concentration (30%) were determined. This method has been applied to study the expression of Mn-SOD mRNA in rat liver after chronic ethanol feeding. Expression of Mn-SOD transcripts was not modified and did not account for the increased Mn-SOD activity. PMID- 27414275 TI - Involvement of bioantioxidants in thrombosis in mice. AB - An involvement of free radicals in thrombosis has been suggested previously. In order to further explore the role of free radicals and antioxidants in thrombosis, we have measured preventive (enzymes of the glutathione redox cycle) and chain-breaking antioxidants (vitamin E and C) in whole blood, platelets, neutrophils (PMNLs), heart and lung following collagen and adrenaline induced thrombosis in mice. A significant decrease in platelet glutathione (GSH) level (54%) and glutathione reductase activity was observed after thrombosis. In addition, GSH content in whole blood was also found to be reduced. In PMNLs, an increase in glutathione peroxidase activity and a four-fold elevation in vitamin C content was observed following thrombosis. However, levels of vitamin E and total thiol groups remained unchanged in both the cells and tissues. The results further suggest involvement of free radicals and PMNLs in thrombosis. PMID- 27414276 TI - Suppressive effect of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats. AB - In order to elucidate the preventive mechanism of molybdenum (Mo) against carcinogenesis of N-nitroso compounds, the effects of in vivo Mo-pretreatment on N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in rats were examined. Effects of in vitro Mo-pretreatment on NDEA-induced DNA strand breaks and fluctuation of the cytosolic free Ca levels in rat hepatocytes were also investigated. Male Wistar rats weighing 170-190 g were pretreated with 10 ppm Mo as Na2MoO4 in deionized drinking water for 21 days, and on day 22, they were exposed to NDEA (50 mg/kg body weight, once, i.p.). 3 and 5 days after NDEA exposure, serum lactic dehydrogenase (LDH) activity, and hepatic calcium (Ca) content and lipid peroxidation levels were evaluated. In vivo Mo-pretreatment prevented NDEA-induced elevations in serum LDH activity and liver Ca content but increased hepatic lipid peroxidation levels. Hepatocytes isolated from rats pretreated with sodium phenobarbital (80 mg/kg body weight, i.p., once a day for 3 days) were exposed to NDEA (0, 100, 250 and 500 MUM) in vitro for 30 min at 37 degrees C. NDEA treatment caused DNA strand breaks and a perturbation of cytosolic free Ca level. However, in vitro Mo-pretreatment (20 MUM, 20 min at 37 degrees C) suppressed the NDEA-induced DNA damage and disruption of intracellular Ca homeostasis. These results suggest Mo protected against NDEA-induced hepatotoxicity by stimulating the metabolism of the nitroso compound via a nontoxic pathway (denitration) while preventing DNA damage connected with alteration in cytosolic free Ca levels. Thus, the general protective action of Mo against N-nitroso compound-induced carcinogenesis may be explained by a common mechanism. PMID- 27414277 TI - The role of glycation and autoxidation on crystallin aggregation. AB - Incubation of alpha-crystallin with glucose and CuSO4 resulted in crystallin changes similar to those observed in cataracts. Examination of the reaction mixtures by polyacrylamide slab gel electrophoresis showed progressive crystallin aggregation through non-disulfide covalent bonds and parallel increases in ultraviolet absorbance and non-tryptophan fluorescence. Both glucose and copper were required; iron was less effective. The reaction can be accelerated by increasing glucose concentration or by utilizing ribose which has a higher percentage of free aldehyde groups than glucose. These observations are consistent with a mechanism involving crystallin glycation. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by chelating agents. These results, in turn, are consistent with copper-catalyzed autoxidation of glucose and of glycated crystallin. This reaction generates superoxide free radical which dismutates to yield hydrogen peroxide. The latter, in turn, generates hydroxyl radicals in presence of transition metal ions (Fenton reaction). Hydroxyl radical attack leads to cross linking which is enhanced in glycated proteins. Under hyperglycemic conditions, such as in diabetes mellitus, high levels of glucose occur in insulin-independent tissues such as the lens. Elevated cupremia and oxidative stress are also known to occur in diabetic patients. There-fore, our findings are consistent with crystallin glycation and superimposed oxyradical generation during diabetic cataractogenesis. PMID- 27414278 TI - Paraquat potentiates iron-induced microsomal lipid peroxidation: modulation by the diet lipid composition. AB - The study concerns the role of two combined factors-lipid composition of the microsomal membranes and the iron concentration in the incubation medium-in lipid peroxidation catalysed by paraquat (P(++)). Rats were subjected to diets containing 5% lipids composed of either tripalmitin (T), peanut oil/rapeseed oil (v/v) (C) or fish oil (F). The level of polyunsaturated fatty acids in the microsomal membranes was higher in C and F than in T. The level of vitamin E was lowest in F. The activity of the system 'Cyt P450-NADPH cyt c reductase' increased in the order T= 0.8 (aOR = 3.04, 95% CI; 1.10-8.44) was significantly associated with MetS, as compared with waist-hip ratio <0.8. The odds of MetS were 22 fold higher in participants with glycated haemoglobin (HbA1c) >= 6.5% (aOR = 22.5, 95% CI; 6.37-79.42) compared to HbA1c <6.5%. This difference was 9 fold higher when HbA1c between 5.6%-6.4% was compared to HbA1c <5.6% (aOR = 8.9, 95% CI; 3.4-23.5). CONCLUSION: The prevalence of MetS among obese Emirati female students was significantly higher than overweight and normal weight students. The high prevalence of MetS highlights the importance of regular screening and intervention programmes targeting weight reduction. PMID- 27414404 TI - Role of targeted agents in neuroendocrine tumors: Results from a meta-analysis. AB - BACKGROUND: Several randomized phase III trials in neuroendocrine tumors (NETs) showed the clinical role of new targeted agents and their impact on tumor response and outcome of whose patients affected by advanced NET. In this study, we summarize the available clinical data related to clinical efficacy of targeted therapies in the treatment of advanced NETs. METHODS: A meta-analysis of randomized studies in accordance with the PRISMA guidelines was performed after searching the databases of PubMed, the Cochrane Library, and the ASCO University Meeting for relevant publications. RESULTS: One thousand 9 hundred and 8 cases were included in the meta-analysis; among these, 1012 were in the experimental arm and 896 were in the control arm. The pooled analysis of the use of target agents in NETs revealed significantly increased of progression free survival compared to control group (hazard ratio = 0.59, 95% CI:0.42-0.84; P = 0.003). Subgroup analysis of patients according to tumor site showed a difference in favor of pancreatic neuroendocrine tumors. Moreover, targeted therapies improved the overall survival (hazard ratio = 0.79, 95%CI: 0.63-0.98; P = 0.03), and response rate (hazard ratio = 3.33, 95% CI 2.02-5.49; P < 0.00001) in all types of NETs. CONCLUSION: Our analysis supports the routine use of targeted agents for treatment of neuroendocrine tumors with particular regards to the pancreatic neuroendocrine tumors. PMID- 27414405 TI - Network Analysis and Visualization of Mouse Retina Connectivity Data. AB - The largest available cellular level connectivity map, of a 0.1 mm sample of the mouse retina Inner Plexiform Layer, was analysed using network models and visualized using spectral graph layouts and observed cell coordinates. This allows key nodes in the network to be identified with retinal neurons. Their strongest synaptic links can trace pathways in the network, elucidating possible circuits. Modular decomposition of the network, by sampling signal flows over nodes and links using the InfoMap method, shows discrete modules of cone bipolar cells that form a tiled mosaic in the retinal plane. The highest flow nodes, calculated by InfoMap, proved to be the most useful landmarks for elucidating possible circuits. Their dominant links to high flow amacrine cells reveal possible circuits linking bipolar through to ganglion cells and show an Off-On discrimination between the Left-Right sections of the sample. Circuits suggested by this analysis confirm known roles for some cells and point to roles for others. PMID- 27414406 TI - Nicotinamide Promotes Adipogenesis in Umbilical Cord-Derived Mesenchymal Stem Cells and Is Associated with Neonatal Adiposity: The Healthy Start BabyBUMP Project. AB - The cellular mechanisms whereby excess maternal nutrition during pregnancy increases adiposity of the offspring are not well understood. However, nicotinamide (NAM), a fundamental micronutrient that is important in energy metabolism, has been shown to regulate adipogenesis through inhibition of SIRT1. Here we tested three novel hypotheses: 1) NAM increases the adipogenic response of human umbilical cord tissue-derived mesenchymal stem cells (MSCs) through a SIRT1 and PPARgamma pathway; 2) lipid potentiates the NAM-enhanced adipogenic response; and 3) the adipogenic response to NAM is associated with increased percent fat mass (%FM) among neonates. MSCs were derived from the umbilical cord of 46 neonates born to non-obese mothers enrolled in the Healthy Start study. Neonatal %FM was measured using air displacement plethysmography (Pea Pod) shortly after birth. Adipogenic differentiation was induced for 21 days in the 46 MSC sets under four conditions, +NAM (3mM)/-lipid (200 MUM oleate/palmitate mix), +NAM/+lipid, -NAM/+lipid, and vehicle-control (-NAM/-lipid). Cells incubated in the presence of NAM had significantly higher PPARgamma protein (+24%, p <0.01), FABP4 protein (+57%, p <0.01), and intracellular lipid content (+51%, p <0.01). Lipid did not significantly increase either PPARgamma protein (p = 0.98) or FABP4 protein content (p = 0.82). There was no evidence of an interaction between NAM and lipid on adipogenic response of PPARgamma or FABP4 protein (p = 0.99 and p = 0.09). In a subset of 9 MSC, SIRT1 activity was measured in the +NAM/-lipid and vehicle control conditions. SIRT1 enzymatic activity was significantly lower ( 70%, p <0.05) in the +NAM/-lipid condition than in vehicle-control. In a linear model with neonatal %FM as the outcome, the percent increase in PPARgamma protein in the +NAM/-lipid condition compared to vehicle-control was a significant predictor (beta = 0.04, 95% CI 0.01-0.06, p <0.001). These are the first data to support that chronic NAM exposure potentiates adipogenesis in human MSCs in vitro, and that this process involves PPARgamma and SIRT1. PMID- 27414408 TI - Accuracy and Calibration of Computational Approaches for Inpatient Mortality Predictive Modeling. AB - Electronic Health Record (EHR) data can be a key resource for decision-making support in clinical practice in the "big data" era. The complete database from early 2012 to late 2015 involving hospital admissions to Inselspital Bern, the largest Swiss University Hospital, was used in this study, involving over 100,000 admissions. Age, sex, and initial laboratory test results were the features/variables of interest for each admission, the outcome being inpatient mortality. Computational decision support systems were utilized for the calculation of the risk of inpatient mortality. We assessed the recently proposed Acute Laboratory Risk of Mortality Score (ALaRMS) model, and further built generalized linear models, generalized estimating equations, artificial neural networks, and decision tree systems for the predictive modeling of the risk of inpatient mortality. The Area Under the ROC Curve (AUC) for ALaRMS marginally corresponded to the anticipated accuracy (AUC = 0.858). Penalized logistic regression methodology provided a better result (AUC = 0.872). Decision tree and neural network-based methodology provided even higher predictive performance (up to AUC = 0.912 and 0.906, respectively). Additionally, decision tree-based methods can efficiently handle Electronic Health Record (EHR) data that have a significant amount of missing records (in up to >50% of the studied features) eliminating the need for imputation in order to have complete data. In conclusion, we show that statistical learning methodology can provide superior predictive performance in comparison to existing methods and can also be production ready. Statistical modeling procedures provided unbiased, well calibrated models that can be efficient decision support tools for predicting inpatient mortality and assigning preventive measures. PMID- 27414407 TI - Learning Is Better with the Hands Free: The Role of Posture in the Memory of Manipulable Objects. AB - Grounded cognition proposes that memory shares processing resources with sensorimotor systems. The aim of the present study was to show that motor simulation participates in the conceptual representation of manipulable objects in long-term memory. In two experiments, lists of manipulable and nonmanipulable objects were presented. Participants were instructed to memorize the items while adopting different postures. In the control condition, they had to keep their hands at rest in front of them. In the interference condition, participants had to keep their hands crossed behind their back to make their hands less free for action. After each list, participants had to perform first a distractive task, and then an oral free recall. The results showed that the interfering posture produced a specific decrease in the recall of manipulable objects, but not of nonmanipulable ones. This decrease was similar when the items were presented as pictures (Experiment 1) or as words (Experiment 2), thus excluding a purely visual effect. These results provide strong evidence that the motor simulation plays a role in the memory trace of the object. PMID- 27414409 TI - Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers-CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin-by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co expression analysis using flow cytometry revealed that CD24+/CD44+/EpCAM+/CD133+ cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24+/CD44+/EpCAM+/CD133+ cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24+/CD44+/EpCAM+/CD133+ cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile. PMID- 27414410 TI - Transdifferentiation and Proliferation in Two Distinct Hemocyte Lineages in Drosophila melanogaster Larvae after Wasp Infection. AB - Cellular immune responses require the generation and recruitment of diverse blood cell types that recognize and kill pathogens. In Drosophila melanogaster larvae, immune-inducible lamellocytes participate in recognizing and killing parasitoid wasp eggs. However, the sequence of events required for lamellocyte generation remains controversial. To study the cellular immune system, we developed a flow cytometry approach using in vivo reporters for lamellocytes as well as for plasmatocytes, the main hemocyte type in healthy larvae. We found that two different blood cell lineages, the plasmatocyte and lamellocyte lineages, contribute to the generation of lamellocytes in a demand-adapted hematopoietic process. Plasmatocytes transdifferentiate into lamellocyte-like cells in situ directly on the wasp egg. In parallel, a novel population of infection-induced cells, which we named lamelloblasts, appears in the circulation. Lamelloblasts proliferate vigorously and develop into the major class of circulating lamellocytes. Our data indicate that lamellocyte differentiation upon wasp parasitism is a plastic and dynamic process. Flow cytometry with in vivo hemocyte reporters can be used to study this phenomenon in detail. PMID- 27414411 TI - Walking Behavior of Zoo Elephants: Associations between GPS-Measured Daily Walking Distances and Environmental Factors, Social Factors, and Welfare Indicators. AB - Research with humans and other animals suggests that walking benefits physical health. Perhaps because these links have been demonstrated in other species, it has been suggested that walking is important to elephant welfare, and that zoo elephant exhibits should be designed to allow for more walking. Our study is the first to address this suggestion empirically by measuring the mean daily walking distance of elephants in North American zoos, determining the factors that are associated with variations in walking distance, and testing for associations between walking and welfare indicators. We used anklets equipped with GPS data loggers to measure outdoor daily walking distance in 56 adult female African (n = 33) and Asian (n = 23) elephants housed in 30 North American zoos. We collected 259 days of data and determined associations between distance walked and social, housing, management, and demographic factors. Elephants walked an average of 5.3 km/day with no significant difference between species. In our multivariable model, more diverse feeding regimens were correlated with increased walking, and elephants who were fed on a temporally unpredictable feeding schedule walked 1.29 km/day more than elephants fed on a predictable schedule. Distance walked was also positively correlated with an increase in the number of social groupings and negatively correlated with age. We found a small but significant negative correlation between distance walked and nighttime Space Experience, but no other associations between walking distances and exhibit size were found. Finally, distance walked was not related to health or behavioral outcomes including foot health, joint health, body condition, and the performance of stereotypic behavior, suggesting that more research is necessary to determine explicitly how differences in walking may impact elephant welfare. PMID- 27414412 TI - Undiscovered Bat Hosts of Filoviruses. AB - Ebola and other filoviruses pose significant public health and conservation threats by causing high mortality in primates, including humans. Preventing future outbreaks of ebolavirus depends on identifying wildlife reservoirs, but extraordinarily high biodiversity of potential hosts in temporally dynamic environments of equatorial Africa contributes to sporadic, unpredictable outbreaks that have hampered efforts to identify wild reservoirs for nearly 40 years. Using a machine learning algorithm, generalized boosted regression, we characterize potential filovirus-positive bat species with estimated 87% accuracy. Our model produces two specific outputs with immediate utility for guiding filovirus surveillance in the wild. First, we report a profile of intrinsic traits that discriminates hosts from non-hosts, providing a biological caricature of a filovirus-positive bat species. This profile emphasizes traits describing adult and neonate body sizes and rates of reproductive fitness, as well as species' geographic range overlap with regions of high mammalian diversity. Second, we identify several bat species ranked most likely to be filovirus-positive on the basis of intrinsic trait similarity with known filovirus-positive bats. New bat species predicted to be positive for filoviruses are widely distributed outside of equatorial Africa, with a majority of species overlapping in Southeast Asia. Taken together, these results spotlight several potential host species and geographical regions as high-probability targets for future filovirus surveillance. PMID- 27414413 TI - Urate transporter URAT1 inhibitors: a patent review (2012 - 2015). AB - INTRODUCTION: Human urate transporter 1 (URAT1, encoded by SLC22A12) has been identified as a key urate transporter expressed at the apical membrane of renal proximal tubule cells for regulating urate homeostasis. Therefore, URAT1 is an attractive target for the development of new uricosurics against hyperuricemia. Discovery of novel inhibitors targeting URAT1 has become a research hotspot in recent years. AREAS COVERED: In this paper, we reviewed the patent applications and related research published during the years 2012-2015, covering the development of URAT1 inhibitors. EXPERT OPINION: There are some promising and inspiring patent applications in this area. Several compounds have superior inhibitory activity of URAT1 with the availability of urate-lowering treatment. For new drug development and commercialization, further studies are needed to evaluate the efficacy and safety. PMID- 27414414 TI - Steady-state pharmacokinetic simulation of intermittent vs. continuous infusion valproic acid therapy in non-critically ill and critically ill patients. AB - OBJECTIVES: Valproic acid (VPA) is a broad-spectrum antiepileptic drug used for a variety of neurologic disorders. The relatively short half-life seen with intermittent intravenous bolus doing may lead to serum concentration variability. Continuous infusion VPA therapy is an approach to mitigate these effects. The objective of this study is to characterize the pharmacokinetics of continuous infusion of VPA in acutely ill patients and to determine dosing regimens that most frequently obtain goal steady-state serum concentrations. METHODS: This is a retrospective pharmacokinetics study in adult patients receiving continuous infusion VPA per institutional protocol for seizure or status migrainosus. Pharmacokinetic parameters were reviewed for 234 patients (25 critically ill) and compared between the two groups (non-critically ill vs. critically ill). Intermittent and continuous infusion dosing strategies were modeled utilizing Monte Carlo simulations for both cohorts. Frequencies of serum concentration attainment were reported. RESULTS: The percent target attainment for the non critically ill group and critically ill group were 69.4 and 58.3% (p = 0.282) post-loading dose and 69.7 and 37.5% (p = 0.004) steady state, respectively. The volume of distribution was significantly different between the two groups (0.35 vs. 0.68 L/kg, p = < 0.0001). Highest frequency of target attainment (50-100 mcg/ml) occurred in the continuous infusion 2 mg/kg/h simulation for both critically ill (45.19%) and acutely ill (48.16%) groups. DISCUSSION: Critically ill patients have an increased volume of distribution. Increasing the volume of distribution requires higher loading doses of VPA to obtain desired therapeutic concentrations. Continuous infusion VPA provides more consistent serum steady state concentrations while mitigating pharmacokinetic variability. PMID- 27414417 TI - Grape Seed Proanthocyanidins Attenuate Anxiety-Like Behavior in an Experimental Model of Dietary-Induced Hypercholesterolemia in Rats. AB - OBJECTIVE: Grape seed proanthocyanidins have many health-protective effects. The present work aimed to assess their possible anxiolytic effects in dietary-induced hypercholesterolemia in rats. METHODS: 30 Male Wistar rats were divided into 3 groups (n = 10): control (normal chow), high cholesterol (cholesterol and cholic acid chow) and high cholesterol + grape seed extract (hypercholesterolemic chow + grape seed extract, 100 mg/kg body weight/day). After 4 months, total cholesterol levels and animals' behavior in the open field and elevated plus maze were assessed. RESULTS: High-cholesterol diet elevated cholesterol levels (p < 0.001 vs control group), however, grape seed administration ameliorated this elevation (p < 0.001 vs high-cholesterol untreated group). In the open field, hypercholesterolemic rats showed increased periods of immobility (138 +/- 20.3 seconds (s) vs 96.9 +/- 14.5 in control rats p < 0.001) and time latency to enter field center (109 +/- 18.3 s compared to 40.8 +/- 10.5 s in the control group p < 0.001). Both parameters were reduced by grape seed treatment (p < 0.01, p < 0.001 vs the untreated hypercholesterolemic group, respectively). Elevated plus maze testing demonstrated higher closed-arm entries (5.5 +/- 1.1 in hypercholesterolemic animals vs 3 +/- 1.1 in the control group p < 0.001) and lower percentage of time spent in open arms (19.7 +/- 3.5 % vs 35.8 +/- 4.8 % in control rats p < 0.001). Grape seed extract significantly enhanced the percentage of time spent in open arms (p < 0.001 compared to hypercholesterolemic rats). CONCLUSION: The present results highlight the possible anxiolytic effect of grape seed proanthocyanidins in dietary-induced hypercholesterolemia. PMID- 27414416 TI - Determining Connections between the Daily Lives of Zoo Elephants and Their Welfare: An Epidemiological Approach. AB - Concerns about animal welfare increasingly shape people's views about the acceptability of keeping animals for food production, biomedical research, and in zoos. The field of animal welfare science has developed over the past 50 years as a method of investigating these concerns via research that assesses how living in human-controlled environments influences the behavior, health and affective states of animals. Initially, animal welfare research focused on animals in agricultural settings, but the field has expanded to zoos because good animal welfare is essential to zoos' mission of promoting connections between animals and visitors and raising awareness of conservation issues. A particular challenge for zoos is ensuring good animal welfare for long-lived, highly social species like elephants. Our main goal in conducting an epidemiological study of African (Loxodonta africana) and Asian (Elephas maximus) elephant welfare in 68 accredited North American zoos was to understand the prevalence of welfare indicators in the population and determine the aspects of an elephant's zoo environment, social life and management that are most important to prevent and reduce a variety of welfare problems. In this overview, we provide a summary of the findings of the nine papers in the collection titled: Epidemiological Investigations of North American Zoo Elephant Welfare with a focus on the life history, social, housing, and management factors found to be associated with particular aspects of elephant welfare, including the performance of abnormal behavior, foot and joint problems, recumbence, walking rates, and reproductive health issues. Social and management factors were found to be important for multiple indicators of welfare, while exhibit space was found to be less influential than expected. This body of work results from the largest prospective zoo-based animal welfare study conducted to date and sets in motion the process of using science-based welfare benchmarks to optimize care of zoo elephants. PMID- 27414415 TI - Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation. AB - Dosage compensation is an essential process that equalizes transcript levels of X linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression. PMID- 27414418 TI - Effects of Pomegranate and Orange Juice on Antioxidant Status in Non-Alcoholic Fatty Liver Disease Patients: A Randomized Clinical Trial. AB - AIM: The fruit of the pomegranate (Punica granatum) has a high content of polyphenols and is renowned for its antioxidant capabilities. In particular, it is recognized as reducing oxidative stress and, therefore, playing a productive role in obstructing the pathogenesis of fatty liver disease. The aim of the present study was to evaluate the effects of consumingpomegranate juice (high in antioxidant content) and orange juice (low in antioxidant content) when combined with a hypocaloric diet on liver enzymes and the antioxidant status of patients. METHODS: In a randomized clinical trial, 65 patients who exhibited non-alcoholic fatty liver disease (NAFLD) at a mean age of 39+/-8 years received 250 mL pomegranate juice or orange juice per day as a substitute for two servings of fruit in a hypocaloric diet over a period of 12 weeks. The subjects' levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total antioxidant capacity (TAC), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-alpha) were measured at the beginning and end of the study. RESULTS: At the end of the study, the levels of liver enzymes and body mass index (BMI) had significantly decreased in both groups. A significant increase in TAC was also observed in the subjects in the pomegranate group (p <0.01). CONCLUSION: Consumption of fruits that are high in antioxidants could represent a useful means to improve the antioxidant status of NAFLD patients who follow a hypocaloric diet. PMID- 27414419 TI - A Systematic Review of Global Alpha-Tocopherol Status as Assessed by Nutritional Intake Levels and Blood Serum Concentrations. AB - The purpose of this study is to systematically review the published literature reporting vitamin E intake levels and serum concentrations in order to obtain a global overview of alpha-tocopherol status. Articles published between 2000 and 2012 were considered; 176 articles referring to 132 single studies were included. Applying an RDA (recommended daily allowance) of 15 mg/day and EAR (estimated average requirement) of 12 mg/day to all populations with a minimum age of 14 years, 82 and 61 % of mean and median data points were below the RDA and the EAR, respectively. Regarding serum concentrations, globally 13 % of the included data points were below the functional deficiency threshold concentration of 12 umol/L, mostly for newborns and children. Several prospective observational studies suggest that a serum alpha-tocopherol concentration of >=30 umol/L has beneficial effects on human health. Of the reported study populations and subpopulations, only 21 % reached this threshold globally. This systematic review suggests that the alpha-tocopherol status is inadequate in a substantial part of the studied populations. PMID- 27414420 TI - The landscape of silence: Sexual violence against men in war. PMID- 27414422 TI - Coming in postgraduate medicine. PMID- 27414421 TI - Comment on Evaluation of Choroidal Vascular Changes in Patients with Multiple Sclerosis Using Enhanced Depth Imaging Optical Coherence Tomography. PMID- 27414423 TI - Problems solutions. PMID- 27414424 TI - Washington background. PMID- 27414425 TI - What's happening in medicine. PMID- 27414426 TI - 1975 Interstate postgraduate medical assembly 60TH Program. PMID- 27414427 TI - Echocardiography. AB - Echocardiography occupies a unique place as an investigative tool in cardiology. This introduction to the technique reviews the basic principles and outlines the diagnosis of common cardiac lesions. Being entirely noninvasive, echocardiography can be repeated to ascertain the severity and observe the progression of cardiac lesions. PMID- 27414429 TI - Therapeutic Index to Advertisers. PMID- 27414430 TI - Association Study and Meta-Analysis of Polymorphisms, Methylation Profiles, and Peripheral mRNA Expression of the Serotonin Transporter Gene in Patients with Alzheimer's Disease. AB - BACKGROUND/AIM: The aim of this study was to elucidate the relationship between Alzheimer's disease (AD) and the serotonin transporter gene (SLC6A4). METHODS: AD subjects (n = 43) and controls (n = 47) were recruited and evaluated. In leukocytes, we evaluated two polymorphisms in SLC6A4, the serotonin transporter length polymorphic region (5-HTT-LPR) and rs25531, as well as methylation rates of the SLC6A4 promoter region and the SLC6A4 mRNA expression level. We also performed a meta-analysis to examine the relationship between the frequency of the L allele and the risk of AD. RESULTS: The distributions of 5-HTT-LPR and rs25531 polymorphisms in AD subjects were not different from those of controls. Although the methylation rates in AD subjects were not significantly different from those of controls, the expression level in AD subjects was significantly higher than in controls. Additionally, the expression level in AD subjects was significantly correlated with apathy. Meta-analysis revealed that the L/L genotype significantly reduced the risk of AD, but only in the Caucasian population. CONCLUSION: Higher SLC6A4 mRNA expression in leukocytes in AD was associated with apathy regardless of SLC6A4 genotypes and methylation rates of the promoter region. The L/L genotype may reduce the risk of AD in the Caucasian population. PMID- 27414431 TI - Cardiovascular Critical Care: Therapeutic Hypothermia, Atrial Fibrillation, and Cardiopulmonary Resuscitation. PMID- 27414432 TI - Asthma in British Columbia: Are we finally breathing easier? A population-based study of the burden of disease over 14 years. AB - OBJECTIVE: Asthma presents a significant global burden, but whether the incidence and prevalence of asthma is rising is still debated. The objective of this study was to determine the prevalence and incidence of asthma in British Columbia (BC), Canada, and characterize associated health services utilization. METHODS: We extracted data from provincial administrative hospitalization, medical services, and prescription drug databases for patients aged 5 to 55 years, during 1996 to 2009 having >=270 MSP registration days and meeting asthma definition of: >=1 hospital admissions with asthma as the principal diagnosis, or >=2 physician visits for asthma as the principal diagnosis, or >=3 asthma drug dispensings. Regression models were used to test change in asthma incidence and prevalence, and use of various health care services, such as physician and emergency department (ED) visits, and hospitalizations. RESULTS: 379,950 patients met the study criteria. The prevalence (2.6%) and incidence (0.7%) of asthma was relatively stable over the study period. There was a decline in proportion of patients visiting family practitioners (FP) (OR 0.92; 95% CI 0.90-0.94), specialists (OR 0.60; 95% CI 0.58-0.62), using ED services (OR 0.31; 95% CI 0.30 0.32) and hospitalizations (OR 0.34; 95% CI 0.31-0.37). Regional differences were noted, with lower rates of FP and specialist visits and higher rates of ED visits for asthma in rural versus urban areas. CONCLUSIONS: In BC, the incidence and prevalence of asthma has remained stable over 14 years. Although health service utilization declined, there is variation between rural and urban regions. PMID- 27414433 TI - Concentrations of neutrophil-derived proteins in meconium and their correlations. AB - AIM: The aim was to measure concentrations of four neutrophil-derived proteins in meconium as biomarkers describing prenatal environment. METHODS: Calprotectin, lactoferrin, myeloperoxidase and PMN-elastase concentrations were measured using ELISA kits in serial meconium portions (n = 81) from 20 healthy neonates. RESULTS: The highest concentration was for calprotectin (286.5 +/- 214.6 ug/g) with a positive correlation (r = 0.75, p < 0.0001) with myeloperoxidase (1.81 +/- 1.72 ug/g). For PMN-elastase (1.70 +/- 2.69 ug/g) a negative correlation was observed with calprotectin and myeloperoxidase (r = -0.51, p < 0.0001; r = -0.60, p < 0.0001, respectively). Concentration of lactoferrin (45.07 +/- 78.53 ug/g) correlated only with that of myeloperoxidese (r = 0.36, p = 0.0009). CONCLUSION: Calprotectin, lactoferrin, myeloperoxidase and PMN-elastase concentrations in meconium are interrelated. These proteins may serve as objective biomarkers describing and/or assessing the intrauterine environment. PMID- 27414435 TI - Statisticians Count. PMID- 27414434 TI - Studying medicine in crisis: Students' perspectives from Syria. PMID- 27414436 TI - Scanning sports. PMID- 27414438 TI - Coming in sportsmedicine. PMID- 27414441 TI - Finding a Niche in Sports Medicine. PMID- 27414442 TI - Wrap-up. PMID- 27414443 TI - Sportsmedicine Forum. AB - A Forum For Our Readers Forum is Intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Forum, THE PHYSICIAN AND SPORTSMEDICINE, 4530W 77th St, Minneapolis, MN 55435. PMID- 27414444 TI - Laughter and the Love of Friends. PMID- 27414445 TI - Peroneal Nerve Palsy Induced by Cryotherapy. AB - A group of experts from the University of California, Los Angeles, met to discuss a case from another institution. This case conference is part of a series featuring a variety of sports medicine topics. PMID- 27414446 TI - How To Help Cardiac Patients Reduce Risk Factors. AB - In brief: People at high risk for myocardial infarction, as well as those who have already sustained one, can use behavior modification to improve their future cardiac health. Yet many continue with unhealthy habits, ignore medical advice, and drop out of valuable rehabilitation programs. An overall restructuring of the process of treating cardiac patients is necessary to help make rehabilitative-and preventive-efforts more effective. This restructuring must include the education of all medical personnel involved in cardiac rehabilitation to convey consistent, unambiguous, and mutually supportive information at each step of the way. PMID- 27414447 TI - Anterior Neck Trauma. AB - In brief: Sports-related injuries to the anterior neck can cause serious airway compromise, requiring life-saving fieldside skills on the part of physicians and trainers covering the event. After reviewing the case of a recreational lacrosse player whose laryngeal injury resulted in severe respiratory distress, the authors discuss field management of anterior neck trauma, including the options for reestablishing an injured athlete's airway and the clinical signs-such as aphonia, hemoptysis, tracheal deviation, or palpable crepitus-that necessitate immediate transport to the hospital. The authors also recommend the use of neck guards to prevent such injuries. PMID- 27414448 TI - Kinematic Magnetic Resonance Imaging for Evaluation of Patellar Tracking. AB - In brief: Kinematic magnetic resonance imaging (MRI) of the patellofemoral joint was r developed to evaluate patellar tracking abnormalities. This technique has several advantages over radiography, eg, it does not expose the patient to ionizing radiation, and it clearly defines the patella and the femoral Cochlea groove without distortion. It also shows the movement of the patella in relation to the trochlea groove at 5 degrees increments of knee flexion up to 30 degrees . This case report demonstrates the value of kinematic MRI in diagnosing excessive lateral pressure syndrome (a frequent cause of knee pain), which cannot be detected by conventional diagnostic 'Paging techniques. PMID- 27414449 TI - Overuse Injuries In Children and Adolescents. AB - In brief: Athletic injuries among children often fall into the category of overuse, with mechanisms similar to overuse injuries in adults. However, the implications for young, growing athletes are much different because the growth plates are involved, resulting in such problems as traction apophysitis and Little League elbow. Early, appropriate intervention, which sometimes includes cessation of certain athletic activity, can prevent potential long-term complications in growing athletes. PMID- 27414450 TI - Bone Scanning for Detection of Exercise-Induced Musculoskeletal Injury. AB - In brief: Bone scans were obtained on 37 entrants in the Western States 100-Mile Endurance Run between 24 hours and one week after the race. Laboratory tests were also performed. The purpose was to determine the degree of muscle and bone damage sustained. The scans of runners who complained of muscle pain showed regions of increased tracer concentration; in most cases the degree of concentration was proportional to the degree of pain experienced. This concentration in the muscle decreased with time after the race-those obtained a week later showed no evidence of abnormality. Enzyme analyses showed markedly increased levels of total CK and CK MB; muscle biopsy specimens indicated myofibrillar lysis and mitochondrial damage. PMID- 27414451 TI - Electrodiagnostic Studies of Median and Ulnar Nerves in Cyclists. AB - In brief: Twenty long-distance cyclists (13 men, 7 women) completed a questionnaire and underwent a neurologic examination and electrodiagnostic studies of the median and ulnar nerves. The purpose was to determine the frequency, severity, and clinical significance of numbness or pain in the hand or wrist and to assess the correlation of electrodiagnostic findings with these complaints. Results of the studies were normal for all 20 cyclists, nine of whom reported symptoms. These cyclists attributed their discomfort to prolonged riding without changing hand position, especially on rough road surfaces. They also reported that their symptoms diminished after they modified their cycling technique and adjusted their bicycle to better fit their body dimensions. PMID- 27414452 TI - Coronary Heart Disease: Risk Profiles of College Football Players. AB - In brief: Before their preseason training, 95 National Collegiate Athletic Association division IA football players were evaluated for several coronary heart disease (CHD) risk factors: blood pressure, serum total cholesterol, high density lipoprotein cholesterol, triglycerides, glucose, percent body fat, family history, cigarette smoking, and aerobic capacity. Offensive linemen had significantly higher mean values for triglycerides, systolic blood pressure, and percent body fat, and lower aerobic capacity. Food records showed that intakes of fat, sugar, cholesterol, and sodium were higher than recommended levels. The data suggest that the large, overfat college football player may have an increased risk of CHD. PMID- 27414453 TI - Don't Rule Out Sports for Hypertensive Children. AB - The author discusses the many factors that can cause a child to be misdiagnosed with hypertension, as well as the kinds of activities that are appropriate for a child who has hypertension. PMID- 27414454 TI - Outwitting Muscle Cramps-Is It Possible? AB - Muscle cramps are common among athletes who regularly work their muscles to the point of exhaustion. And some athletes will resort to anything to get rid of them. PMID- 27414455 TI - Fibromyalgia: Is Exercise the Cause or the Cure? AB - The enigmatic condition we now call fibromyalgia has no known cause, diagnostic test, or cure. And though it never goes away completely, exercise may make it easier to live with. PMID- 27414457 TI - Joe Montana: Back Exercises for a Super Bowl Winner. PMID- 27414456 TI - Back Pain Prescription: Out of Bed and Into the Gym. AB - Bed rest and pain pills, the traditional remedies for back strains and sprains, don't always work. Physicians are looking at alternatives like exercise to get patients out of bed and moving again. PMID- 27414458 TI - Exercise adviser. PMID- 27414459 TI - Initial Management of the Sports Emergency. PMID- 27414461 TI - Preventive Services Use Among African American and Latino Adult Caregivers in South Los Angeles. AB - BACKGROUND: The burden of informal caregiving is significant and well-documented, yet the evidence is mixed as to whether being a caregiver presents an additional barrier to receiving recommended preventive care. OBJECTIVES: To determine whether (1) caregivers compared with noncaregivers were less likely to receive preventive health services; and (2) higher intensity caregivers were less likely to receive preventive health services than lower intensity caregivers. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Data were from a telephone survey of Latino and African American adults 50 years or older in South Los Angeles (n=702). Outcomes were flu vaccination, pneumococcal vaccination, and colorectal cancer screening. Logistic regression models adjusted for predisposing, enabling, and need factors according to the Andersen Model of Access to Health Care for Low-income Populations. RESULTS: Caregiver type (eg, adult child, nonrelated) was associated with varying odds of receiving a preventive service. Caregivers had lower odds than noncaregivers of receiving preventive services although odds of receiving a flu vaccination improved slightly for caregivers of persons with memory loss compared with other caregivers. More weekly caregiving hours was associated with higher odds of receiving flu vaccination (adjusted odds ratios, 1.1; 95% confidence interval=1.0, 1.1) or colorectal cancer screening (adjusted odds ratios, 1.1; 95% confidence interval=1.0, 1.1). Caregivers and noncaregivers age 65 and older or with chronic conditions were more likely to receive vaccinations. CONCLUSIONS: Preventive service use was influenced by characteristics of the caregiving situation. An opportunity may exist to leverage care recipients' ongoing contact with health care providers to increase caregivers' own access to preventive services. PMID- 27414462 TI - Understanding of a negative bowel screening result and potential impact on future symptom appraisal and help-seeking behaviour: a focus group study. AB - BACKGROUND: Colorectal cancer (CRC) screening using a faecal occult blood test (FOBt) has the potential to reduce cancer-related mortality. Symptom vigilance remains crucial as a proportion of cancers will be diagnosed between screening rounds. A negative FOBt has the potential to influence how participants respond to future symptoms of CRC. OBJECTIVE: To explore (i) understanding of a negative FOBt and (ii) the potential impact of a negative FOBt upon future symptom appraisal and help-seeking behaviour. DESIGN: Qualitative methodology utilizing focus groups with participants who received a negative FOBt within the National Bowel Cancer Screening Programme in Coventry and Lothian. Topics explored included: experience of screening participation, interpretation and understanding of a negative result, symptom awareness and attitudes towards help-seeking. RESULTS: Four broad themes were identified: (i) emotional response to a negative FOBt, (ii) understanding the limitations of FOBt screening, (iii) symptom knowledge and interpretation and (iv) over-reassurance from a negative FOBt. Participants were reassured by a negative FOBt, but there was variability in the extent to which the result was interpreted as an "all clear". Some participants acknowledged the residual risk of cancer and the temporal characteristic of the result, while others were surprised that the result was not a guarantee that they did not have cancer. DISCUSSION AND CONCLUSIONS: Participants recognized that reassurance from a negative FOBt could lead to a short-term delay in help-seeking if symptoms developed. Screening programmes should seek to emphasize the importance of the temporal nature of FOBt results with key messages about symptom recognition and prompt help-seeking behaviour. PMID- 27414463 TI - BAG3 Protein Is Over-Expressed in Endometrioid Endometrial Adenocarcinomas. AB - Endometrioid endometrial cancer is the most common gynaecological tumor in developed countries, and its incidence is increasing. The definition of subtypes, based on clinical and endocrine features or on histopathological characteristics, correlate to some extent with patient's prognosis, but there is substantial heterogeneity within tumor types. The search for molecules and mechanisms implied in determining the progression and the response to therapy for this cancer is still ongoing. BAG3 protein, a member of BAG family of co-chaperones, has a pro survival role in several tumor types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby, modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. BAG3 expression in human endometrial cancer tissues was not investigated so far. Here, we show that BAG3 protein levels are elevated in tumoral and hyperplastic cells in respect to normal glands. Furthermore, BAG3 subcellular localization appears to be changed in tumoral compared to normal cells. Our results indicate a possible role for BAG3 protein in the maintenance of cell survival in endometrioid endometrial cancer and suggest that this field of studies is worthy of further investigations. J. Cell. Physiol. 232: 309-311, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27414464 TI - 4D in vivo imaging of glomerular barrier function in a zebrafish podocyte injury model. AB - AIM: Zebrafish larvae with their simplified pronephros are an ideal model to study glomerular physiology. Although several groups use zebrafish larvae to assess glomerular barrier function, temporary or slight changes are still difficult to measure. The aim of this study was to investigate the potential of in vivo two-photon microscopy (2-PM) for long-term imaging of glomerular barrier function in zebrafish larvae. METHODS: As a proof of principle, we adapted the nitroreductase/metronidazole model of targeted podocyte ablation for 2-PM. Combination with a strain, which expresses eGFP-vitamin D-binding protein in the blood plasma, led to a strain that allowed induction of podocyte injury with parallel assessment of glomerular barrier function. We used four-dimensional (4D) 2-PM to assess eGFP fluorescence over 26 h in the vasculature and in tubules of multiple zebrafish larvae (5 days post-fertilization) simultaneously. RESULTS: By 4D 2-PM, we observed that, under physiological conditions, eGFP fluorescence was retained in the vasculature and rarely detected in proximal tubule cells. Application of metronidazole induced podocyte injury and cell death as shown by TUNEL staining. Induction of podocyte injury resulted in a dramatic decrease of eGFP fluorescence in the vasculature over time (about 50% and 90% after 2 and 12 h respectively). Loss of vascular eGFP fluorescence was paralleled by an endocytosis-mediated accumulation of eGFP fluorescence in proximal tubule cells, indicating proteinuria. CONCLUSION: We established a microscopy-based method to monitor the dynamics of glomerular barrier function during induction of podocyte injury in multiple zebrafish larvae simultaneously over 26 h. PMID- 27414465 TI - An insight into polymerization-induced self-assembly by dissipative particle dynamics simulation. AB - Polymerization-induced self-assembly is a one-pot route to produce concentrated dispersions of block copolymer nano-objects. Herein, dissipative particle dynamics simulations with a reaction model were employed to investigate the behaviors of polymerization-induced self-assembly. The polymerization kinetics in the polymerization-induced self-assembly were analyzed by comparing with solution polymerization. It was found that the polymerization rate enhances in the initial stage and decreases in the later stage. In addition, the effects of polymerization rate, length of macromolecular initiators, and concentration on the aggregate morphologies and formation pathway were studied. The polymerization rate and the length of the macromolecular initiators are found to have a marked influence on the pathway of the aggregate formations and the final structures. Morphology diagrams were mapped correspondingly. A comparison between simulation results and experimental findings is also made and an agreement is shown. This work can enrich our knowledge about polymerization-induced self-assembly. PMID- 27414466 TI - Effect of ursolic acid in attenuating chronic constriction injury-induced neuropathic pain in rats. AB - Ursolic acid (UA; 3b-hydroxy-12-urs-12-en-28-oic acid), a natural pentacyclic triterpenoid carboxylic acid, has been known to possess potent anti-inflammatory, antioxidant, and antinociceptive effects in various animal models. Therefore, this study was designed to investigate the antihyperalgesic, anti-inflammatory, and antioxidant effects of UA at 5, 10, and 20 mg/kg of doses via per os (p.o.) route for 14 days in chronic constriction injury (CCI)-induced neuropathic pain in rats. Pain behavior in rats was evaluated before and after UA administration via mechanical and heat hyperalgesia. CCI caused significant increase in levels of pro-inflammatory cytokines and oxido-nitrosative stress. In addition, significant increase in myeloperoxidase, malondialdehyde, protein carbonyl, nitric oxide (NO), and total oxidant status (TOS) levels in sciatic nerve and spinal cord concomitant with mechanical and heat hyperalgesia is also noted for CCI-induced neuropathic pain. Administration of UA significantly reduced the increased levels of pro-inflammatory cytokines and TOS. Further, reduced glutathione is also restored by UA. UA also showed in vitro NO and superoxide radical scavenging activity. UA has a potential in attenuating neuropathic pain behavior in CCI model which may possibly be attributed to its anti-inflammatory and antioxidant properties. PMID- 27414467 TI - Separation of enzymatic functions and variation of spin state of rice allene oxide synthase-1 by mutation of Phe-92 and Pro-430. AB - Rice allene oxide synthase-1 mutants carrying F92L, P430A or F92L/P430A amino acid substitution mutations were constructed, recombinant mutant and wild type proteins were purified and their substrate preference, UV-vis spectra and heme iron spin state were characterized. The results show that the hydroperoxide lyase activities of F92L and F92L/P430A mutants prefer 13-hydroperoxy substrate to other hydroperoxydienoic acids or hydroperoxytrienoic acids. The Soret maximum was completely red-shifted in P430A and F92L/P430A mutants, but it was partially shifted in the F92L mutant. ESR spectral data showed that wild type, F92L and P430A mutants occupied high and low spin states, while the F92L/P430A mutant occupied only low spin state. The extent of the red shift of the Soret maximum increased as the population of low spin heme iron increased, suggesting that the spectral shift reflects the high to low transition of heme iron spin state in rice allene oxide synthase-1. Relative to wild type allene oxide synthase-1, the hydroperoxide lyase activities of F92L and F92L/P430A are less sensitive to inhibition by imidazole with (13S or 9S)-hydroperoxydienoic acid as substrate and more sensitive than wild type with (13S)-hydroperoxytrienoic acid as substrate. Our results suggest that hydroperoxydienoic acid is the preferred substrate for the hydroperoxide lyase activity and (13S)-hydroperoxytrienoic acid is the preferred substrate for allene oxide synthase activity of allene oxide synthase 1. PMID- 27414468 TI - Synthesis of novel disulfide and sulfone hybrid scaffolds as potent beta glucuronidase inhibitor. AB - Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for beta-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent beta-glucuronidase inhibitory potential with IC50 value ranging in between 2.20 88.16MUM as compared to standard d-saccharic acid 1,4 lactone (48.4+/-1.25MUM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against beta-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies. PMID- 27414469 TI - Intimate partner stalking: Contributions to PTSD symptomatology among a national sample of women veterans. AB - OBJECTIVES: Women veterans are at high risk for intimate partner violence (IPV), which has previously been defined as psychological, physical, or sexual violence from an intimate partner. The Centers for Disease Control and Prevention recently added stalking to its uniform definition of IPV, but little is known about the occurrence of stalking victimization among women veterans who experience IPV, its overlap with other forms of IPV, and its contribution to posttraumatic stress disorder (PTSD) symptomatology among this population. METHODS: Lifetime intimate partner stalking, as well as physical, sexual, and psychological IPV, was assessed as part of a larger study of women veterans who completed a 2014 Web based survey (75% participation rate). Women with a history of IPV or stalking (55%, n = 225) completed the PTSD Checklist-5 to assess PTSD symptoms related to IPV and items assessing military sexual trauma and combat exposure. RESULTS: Among 225 women veterans with a history of IPV, approximately 64% (n = 145) reported lifetime stalking by an intimate partner. Women who experienced both stalking and other forms of IPV were 4.2 times more likely to experience probable PTSD than were women who experienced IPV without stalking, odds ratio (OR) = 4.18, 95% confidence interval (CI) [1.91, 9.13]. After adjusting for military sexual trauma and lifetime sum of other types of IPV, women who experienced partner stalking remained 2.5 times more likely than women without a history of partner stalking to experience probable PTSD, OR = 2.49, 95% CI [1.07, 5.78]. CONCLUSIONS: Stalking from an intimate partner is a common form of IPV experienced by women veterans that strongly contributes to risk for probable PTSD. In addition to other forms of IPV, identification and treatment efforts should attend to stalking victimization among this rapidly growing population. (PsycINFO Database Record PMID- 27414470 TI - The art and skill of delivering culturally responsive trauma-focused cognitive behavioral therapy in Tanzania and Kenya. AB - OBJECTIVE: This study explored the facilitators, barriers, and strategies used to deliver a child mental health evidence-based treatment (EBT), trauma-focused cognitive behavioral therapy (TF-CBT), in a culturally responsive manner. In low- and middle-income countries most individuals with mental health problems do not receive treatment due to a shortage of mental health professionals. One approach to addressing this problem is task-sharing, in which lay counselors are trained to deliver mental health treatment. Combining this approach with a focus on EBT provides a strategy for bridging the mental health treatment gap. However, little is known about how western-developed EBTs are delivered in a culturally responsive manner. METHOD: Semistructured qualitative interviews were conducted with 12 TF-CBT lay counselors involved in a large randomized controlled trial of TF-CBT in Kenya and Tanzania. An inductive approach was used to analyze the data. RESULTS: Lay counselors described the importance of being responsive to TF-CBT participants' customs, beliefs, and socioeconomic conditions and highlighted the value of TF-CBT for their community. They also discussed the importance of partnering with other organizations to address unmet socioeconomic needs. CONCLUSION: The findings from this study provide support for the acceptability and appropriateness of TF-CBT as a treatment approach for improving child mental health. Having a better understanding of the strategies used by lay counselors to ensure that treatment is relevant to the cultural and socioeconomic context of participants can help to inform the implementation of future EBTs. (PsycINFO Database Record PMID- 27414471 TI - Hearing protector fit testing with off-shore oil-rig inspectors in Louisiana and Texas. AB - OBJECTIVE: This field study aimed to assess the noise reduction of hearing protection for individual workers, demonstrate the effectiveness of training on the level of protection achieved, and measure the time required to implement hearing protector fit testing in the workplace. DESIGN: The National Institute for Occupational Safety and Health (NIOSH) conducted field studies in Louisiana and Texas to test the performance of HPD Well-Fit. STUDY SAMPLE: Fit tests were performed on 126 inspectors and engineers working in the offshore oil industry. RESULTS: Workers were fit tested with the goal of achieving a 25-dB PAR. Less than half of the workers were achieving sufficient protection from their hearing protectors prior to NIOSH intervention and training; following re-fitting and re training, over 85% of the workers achieved sufficient protection. Typical test times were 6-12 minutes. CONCLUSIONS: Fit testing of the workers' earplugs identified those workers who were and were not achieving the desired level of protection. Recommendations for other hearing protection solutions were made for workers who could not achieve the target PAR. The study demonstrates the need for individual hearing protector fit testing and addresses some of the barriers to implementation. PMID- 27414472 TI - Pro-insecticidal approach towards increasing in planta activity. AB - BACKGROUND: The adrenergic mode of action was investigated for the development of potential new insecticides. Clonidine-related analogs were tested against Myzus persicae (Sulzer) and Bemisia tabaci (Gennadius). Clonidine analogs lack translation owing to a possible vacuole-trapping mechanism. Physical property modulation via a prodrug approach was attempted to overcome this mechanism. RESULTS: Clonidine showed insecticidal activity against M. persicae and B. tabaci. A prodrug of a known open-chain analog of clonidine was developed. While the prodrug had decreased pKa and increased lipophilicity and displayed good activity against M. persicae B. tabaci, the activity did not translate to cotton. Metabolic studies showed that the prodrug was quickly metabolized to the parent compound, and was further metabolized to a known vacuole-trapped oxazoline analog. CONCLUSIONS: Adrenergic active compounds, such as clonidine analogs, show potential as insecticides; however, a designed prodrug approach did not overcome the lack of translation in this case. Studies confirmed that the synthesized prodrug analog metabolized in planta to the proposed vacuole-trapped compound. One possible explanation for the failure of this approach is that the rate of metabolism and vacuole trapping is faster than translaminar flow, and therefore the released pesticide is not biologically available to the target organism. (c) 2016 Society of Chemical Industry. PMID- 27414473 TI - Ultrasensitive Glutathione Detection Based on Lucigenin Cathodic Electrochemiluminescence in the Presence of MnO2 Nanosheets. AB - Glutathione (GSH) is a crucial antioxidant produced endogenously and plays key roles in biological systems. It is vitally important to design simple, selective, and sensitive methods to sense GSH and monitor changes of GSH concentration. In this work, the cathodic electrochemiluminescence (ECL) of lucigenin in the presence of MnO2 nanosheets at a glassy carbon electrode was utilized for GSH detection. GSH can reduce MnO2 nanosheets into Mn(2+) which can obviously inhibit the ECL of lucigenin. The ECL inhibition efficiencies increase linearly with the concentrations of glutathione in the range of 10 to 2000 nM. The detection limit for GSH measurement is 3.7 nM. This proposed method is highly sensitive, selective, simple, fast, and cost-effective. Moreover, this approach can detect GSH in human serum samples with excellent recoveries, which indicates its promising application under physiological conditions. PMID- 27414474 TI - Renal pathology in patients with occupational exposure to carbon disulphide: A case series. AB - AIM: Carbon disulphide (CS2 ) is widely used as an organic solvent. However, there is little information available regarding the clinical manifestations and the pathological features of kidney injury caused by CS2 . The current study aimed to describe the renal manifestations of a group of patients with long-term occupational exposure to CS2 . METHODS: Ten patients with long-term exposure to CS2 and visiting a single centre were enrolled, with their clinical features recorded. Renal biopsies were taken from all patients, and their pathological findings were documented. RESULTS: All patients came from the same chemical fibre factory. Their mean age at enrollment was 36.9 +/- 2.4 years, and each patient had a CS2 exposure duration exceeding 10 years. Eight patients (80%) presented with proteinuria and none had hematuria. Two patients (20%) had underlying hypertension and five (50%) had increased serum creatinine levels. Light microscopic examination of their renal biopsy specimens revealed diffuse mesangial cell proliferation and mesangial hyperplasia in all patients. Moreover, three patients (30%) had nodular hyperplasia, resembling the lesions of diabetic nephropathy. Variable degrees of tubular atrophy and interstitial infiltrations of lymphocytes and monocytes were observed in all patients. Similarly, lectron microscopic examination showed glomerular mesangial cell proliferation and mesangial hyperplasia. Immunopathological staining for IgA and IgG, complements or hepatitis B markers (hepatitis B surface antigen and e antigen-antibody) are negative in all patients. CONCLUSION: Long-term occupational exposure to CS2 may be associated with renal injury, although the renal pathological features are often non-specific. PMID- 27414476 TI - Acetaminophen-Induced Changes in Systemic Blood Pressure in Critically Ill Patients: Results of a Multicenter Cohort Study. AB - OBJECTIVES: We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication. DESIGN: Prospective observational study. SETTING: Three ICUs. PATIENTS: Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline. RESULTS: Overall, 160 patients were included in this study. Eighty-three patients (51.9%) experienced acetaminophen-induced hypotension according to our definition. In patients with acetaminophen-induced hypotension, the nadir mean arterial pressure was 64 mm Hg (95% CI, 54-74). Hypotension was observed 30 minutes (95% CI, 15-71) after acetaminophen infusion. Changes in mean arterial pressure were closely correlated with decreases in the diastolic arterial pressure (r = 0.92) and to a lesser extent with changes in the pulse pressure (r = 0.18) and heart rate (r = 0.09). Changes in the body temperature were not correlated with changes in mean arterial pressure (r = 0.0002; p = 0.85). None of the patients' baseline characteristics (shock, use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, lactates, renal replacement therapy, chronic heart disease, and indication for acetaminophen infusion) or clinically relevant characteristics (baseline severity according to Logistic Organ Dysfunction score, need for vasopressors, use of antihypertensive agents, need for mechanical ventilation, or changes in the body temperature) were independently associated with acetaminophen induced hypotension. Among patients with acetaminophen-induced hypotension, 29 (34.9%) required therapeutic intervention. CONCLUSIONS: Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved. PMID- 27414477 TI - Prognostic Value of Secretoneurin in Critically Ill Patients With Infections. AB - OBJECTIVES: Secretoneurin is produced in neuroendocrine cells, and the myocardium and circulating secretoneurin levels provide incremental prognostic information to established risk indices in cardiovascular disease. As myocardial dysfunction contributes to poor outcome in critically ill patients, we wanted to assess the prognostic value of secretoneurin in two cohorts of critically ill patients with infections. DESIGN: Two prospective, observational studies. SETTING: Twenty-four and twenty-five ICUs in Finland. PATIENTS: A total of 232 patients with severe sepsis (cohort #1) and 94 patients with infections and respiratory failure (cohort #2). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured secretoneurin levels by radioimmunoassay in samples obtained early after ICU admission and compared secretoneurin with other risk indices. In patients with severe sepsis, admission secretoneurin levels (logarithmically transformed) were associated with hospital mortality (odds ratio, 3.17 [95% CI, 1.12-9.00]; p = 0.030) and shock during the hospitalization (odds ratio, 2.17 [1.06-4.46]; p = 0.034) in analyses that adjusted for other risk factors available on ICU admission. Adding secretoneurin levels to age, which was also associated with hospital mortality in the multivariate model, improved the risk prediction as assessed by the category-free net reclassification index: 0.35 (95% CI, 0.06 0.64) (p = 0.02). In contrast, N-terminal pro-B-type natriuretic peptide levels were not associated with mortality in the multivariate model that included secretoneurin measurements, and N-terminal pro-B-type natriuretic peptide did not improve patient classification on top of age. Secretoneurin levels were also associated with hospital mortality after adjusting for other risk factors and improved patient classification in cohort #2. In both cohorts, the optimal cutoff for secretoneurin levels at ICU admission to predict hospital mortality was ~ 175 pmol/L, and higher levels were associated with mortality also when adjusting for Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. CONCLUSIONS: Secretoneurin levels provide incremental information to established risk indices for the prediction of mortality and shock in critically ill patients with severe infections. PMID- 27414478 TI - Partial Nephrogenic Diabetes Insipidus in a Burned Patient Receiving Sevoflurane Sedation With an Anesthetic Conserving Device-A Case Report. AB - OBJECTIVE: To describe a case of partial nephrogenic diabetes insipidus in a burned patient after prolonged delivery of low inspired concentrations of sevoflurane via an Anesthetic Conserving Device. DATA SOURCES: Clinical observation. STUDY SELECTION: Case report. DATA EXTRACTION: Relevant clinical information. DATA SYNTHESIS: A 34-year-old man was admitted with burns covering 52% of his total body surface area. Mechanical ventilation was provided during sedation with continuous infusions of sufentanil and midazolam. Sedation became increasingly difficult, and in order to limit administration of IV agents, sevoflurane was added to the inspiratory gas flow. This was provided using an Anesthetic Conserving Device and continued for 8 days. The patient rapidly developed polyuria and hypernatremia with an inappropriate decrease in urinary osmolality. Administration of desmopressin resulted in only a modest effect on renal concentrating ability. After cessation of sevoflurane, all variables returned to normal within 5 days. The results of further investigations (cerebral computed tomographic scan, cerebral magnetic resonance imaging, and serum arginine vasopressin concentration) were compatible with a diagnosis of partial nephrogenic diabetes insipidus. The temporal sequence of clinical findings in relation to sevoflurane administration suggests that the sevoflurane was the probable underlying cause. CONCLUSIONS: Clinicians should be aware of the possibility of sevoflurane-induced diabetes insipidus not only during general anesthesia but also in the intensive care setting of sedation in critically ill patients. This is especially important in patients, such as those with severe burns, in whom preserved renal concentrating ability is important to ensure compensation for extrarenal fluid losses. PMID- 27414480 TI - Wafer-Scale Single-Crystalline AB-Stacked Bilayer Graphene. AB - Single-crystalline artificial AB-stacked bilayer graphene is formed by aligned transfer of two single-crystalline monolayers on a wafer-scale. The obtained bilayer has a well-defined interface and is electronically equivalent to exfoliated or direct-grown AB-stacked bilayers. PMID- 27414479 TI - Blood Pressure- and Coronary Perfusion Pressure-Targeted Cardiopulmonary Resuscitation Improves 24-Hour Survival From Ventricular Fibrillation Cardiac Arrest. AB - OBJECTIVES: Treatment algorithms for cardiac arrest are rescuer centric and vary little from patient to patient. The objective of this study was to determine if cardiopulmonary resuscitation-targeted to arterial blood pressure and coronary perfusion pressure rather than optimal guideline care would improve 24-hour survival in a porcine model of ventricular fibrillation cardiac arrest. DATA SOURCES: Preclinical animal laboratory using female 3-month-old swine. STUDY SELECTION: A randomized interventional study. DATA EXTRACTION: After induction of anesthesia and 7 minutes of untreated ventricular fibrillation, 16 female 3-month old swine were randomized to 1) blood pressure care: titration of chest compression depth to a systolic blood pressure of 100 mm Hg and vasopressor dosing to maintain coronary perfusion pressure of greater than 20 mm Hg or 2) guideline care: chest compression depth targeted to 51 mm and standard guideline vasopressor dosing. Animals received manual cardiopulmonary resuscitation for 10 minutes before the first defibrillation attempt and standardized postresuscitation care for 24 hours. DATA SYNTHESIS: Twenty-four-hour survival was more likely with blood pressure care versus guideline care (0/8 vs 5/8; p < 0.03), and all survivors had normal neurologic examinations. Mean coronary perfusion pressure prior to defibrillation was significantly higher with blood pressure care (28 +/- 3 vs 10 +/- 6 mm Hg; p < 0.01). Chest compression depth was lower with blood pressure care (48 +/- 0.4 vs 44 +/- 0.5 mm Hg; p < 0.05), and the number of vasopressor doses was higher with blood pressure care (median, 3 [range, 1-7] vs 2 [range, 2-2]; p < 0.01). CONCLUSIONS: Individualized goal directed hemodynamic resuscitation targeting systolic blood pressure of 100 mm Hg and coronary perfusion pressure of greater than 20 mm Hg improved 24-hour survival compared with guideline care in this model of ventricular fibrillation cardiac arrest. PMID- 27414481 TI - Consensus on surgical aspects of managing osteomyelitis in the diabetic foot. AB - BACKGROUND: The aim of this study was to develop consensus statements that may help share or even establish 'best practices' in the surgical aspects of managing diabetic foot osteomyelitis (DFO) that can be applied in appropriate clinical situations pending the publication of more high-quality data. METHODS: We asked 14 panelists with expertise in DFO management to participate. Delphi methodology was used to develop consensus statements. First, a questionnaire elicited practices and beliefs concerning various aspects of the surgical management of DFO. Thereafter, we constructed 63 statements for analysis and, using a nine point Likert scale, asked the panelists to indicate the extent to which they agreed or disagreed with the statements. We defined consensus as a mean score of greater than 7.0. RESULTS: The panelists reached consensus on 38 items after three rounds. Among these, seven provide guidance on initial diagnosis of DFO and selection of patients for surgical management. Another 15 statements provide guidance on specific aspects of operative management, including the timing of operations and the type of specimens to be obtained. Ten statements provide guidance on postoperative management, including wound closure and offloading, and six statements summarize the panelists' agreement on general principles for surgical management of DFO. CONCLUSIONS: Consensus statement on the perioperative management of DFO were formed with an expert panel comprised of a variety of surgical specialties. We believe these statements may serve as 'best practice' guidelines until properly performed studies provide more robust evidence to support or refute specific surgical management steps in DFO. PMID- 27414482 TI - Effects of sediment-spiked lufenuron on benthic macroinvertebrates in outdoor microcosms and single-species toxicity tests. AB - Sediment ecotoxicity studies were conducted with lufenuron to (i) complement the results of a water-spiked mesocosm experiment with this lipophilic benzoylurea insecticide, (ii) to explore the predictive value of laboratory single-species tests for population and community-level responses of benthic macroinvertebrates, and (iii) to calibrate the tier-1 effect assessment procedure for sediment organisms. For this purpose the concentration-response relationships for macroinvertebrates between sediment-spiked microcosms and those of 28-d sediment spiked single-species toxicity tests with Chironomus riparius, Hyalella azteca and Lumbriculus variegatus were compared. Lufenuron persisted in the sediment of the microcosms. On average, 87.7% of the initial lufenuron concentration could still be detected in the sediment after 12 weeks. Overall, benthic insects and crustaceans showed treatment-related declines and oligochaetes treatment-related increases. The lowest population-level NOEC in the microcosms was 0.79MUg lufenuron/g organic carbon in dry sediment (MUg a.s./g OC) for Tanytarsini, Chironomini and Dero sp. Multivariate analysis of the responses of benthic macroinvertebrates revealed a community-level NOEC of 0.79MUg a.s./g OC. The treatment-related responses observed in the microcosms are in accordance with the results of the 28-d laboratory toxicity tests. These tests showed that the insect C. riparius and the crustacean H. azteca were approximately two orders of magnitude more sensitive than the oligochaete L. variegatus. In our laboratory tests, using field-collected sediment, the lowest 28-d EC10 (0.49MUg a.s./g OC) was observed for C. riparius (endpoint survival), while for the standard OECD test with this species, using artificial sediment, a NOEC of 2.35MUg a.s./g OC (endpoint emergence) is reported. In this particular case, the sediment tier-1 effect assessment using the chronic EC10 (field-collected sediment) or chronic NOEC (artificial sediment) of C. riparius and an assessment factor of 10, seems to be protective for the treatment-related responses observed in the sediment spiked microcosms. PMID- 27414483 TI - Using SANS with Contrast-Matched Lipid Bicontinuous Cubic Phases To Determine the Location of Encapsulated Peptides, Proteins, and Other Biomolecules. AB - An understanding of the location of peptides, proteins, and other biomolecules within the bicontinuous cubic phase is crucial for understanding and evolving biological and biomedical applications of these hybrid biomolecule-lipid materials, including during in meso crystallization and drug delivery. While theoretical modeling has indicated that proteins and additive lipids might phase separate locally and adopt a preferred location in the cubic phase, this has never been experimentally confirmed. We have demonstrated that perfectly contrast matched cubic phases in D2O can be studied using small-angle neutron scattering by mixing fully deuterated and hydrogenated lipid at an appropriate ratio. The model transmembrane peptide WALP21 showed no preferential location in the membrane of the diamond cubic phase of phytanoyl monoethanolamide and was not incorporated in the gyroid cubic phase. While deuteration had a small effect on the phase behavior of the cubic phase forming lipids, the changes did not significantly affect our results. PMID- 27414484 TI - [Dysphonia and Dysphagia Caused by a Pedunculated Polyp of the Hypopharynx]. PMID- 27414485 TI - The expanding regulatory network of STING-mediated signaling. AB - The identification and characterization of DNA-sensing pathways has been a subject of intensive investigation for the last decade. This interest, in part, is supported by the fact that the main outcome of DNA-responses is production of type I interferon (IFN-I), which, if produced in excessive amounts, leads to various pathologies. STING (stimulator of interferon genes) is positioned in the center of these responses and is activated either via direct sensing of second messengers or via interaction with upstream sensors of dsDNA. STING mediates responses to pathogens as well as host-derived DNA and is, therefore, linked to various autoimmune diseases, cancer predisposition and ageing. Recent mouse models of DNA damage showed the adaptor STING to be crucial for heightened resting levels of IFN-I. In this review, we will focus on recent advances in understanding the regulation of STING-signaling and identification of its novel components. PMID- 27414486 TI - A five-gene expression signature to predict progression in T1G3 bladder cancer. AB - OBJECTIVE: The aim of this study was to analyze tumour gene expression profiles of progressive and non-progressive T1G3 bladder cancer (BC) patients to develop a gene expression signature to predict tumour progression. METHODS: Retrospective, multicenter study of 96 T1G3 BC patients without carcinoma in situ (CIS) who underwent a transurethral resection. Formalin-fixed paraffin-embedded tissue samples were collected. Global gene expression patterns were analyzed in 21 selected samples from progressive and non-progressive T1G3 BC patients using Illumina microarrays. Expression levels of 94 genes selected based on microarray data and based on literature were studied by quantitative polymerase chain reaction (qPCR) in an independent series of 75 progressive and non-progressive T1G3 BC patients. Univariate logistic regression was used to identify individual predictors. A variable selection method was used to develop a multiplex biomarker model. Discrimination of the model was measured by area under the receiver operating characteristic curve. Interaction networks between the genes of the model were built by GeneMANIA Cytoscape plugin. RESULTS: A total of 1294 genes were found differentially expressed between progressive and non-progressive patients. Differential expression of 15 genes was validated by qPCR in an additional set of samples. A five-gene expression signature (ANXA10, DAB2, HYAL2, SPOCD1, and MAP4K1) discriminated progressive from non-progressive T1G3 BC patients with a sensitivity of 79% and a specificity of 86% (AUC = 0.83). Direct interactions between the five genes of the model were not found. CONCLUSIONS: Progressive and non-progressive T1G3 bladder tumours have shown different gene expression patterns. To identify T1G3 BC patients with a high risk of progression, a five-gene expression signature has been developed. PMID- 27414488 TI - Deposition of radiocesium on the river flood plains around Fukushima. AB - The environment in the area around Fukushima Daiichi Nuclear Power Plant has been contaminated by widely deposited significant amount of radioactive materials, which were released to the atmosphere caused by the Fukushima Daiichi Nuclear Power Plant accident due to the Great East Japan Earthquake, which occurred on March 11, 2011. The radiocesium released in the accident mainly affects radiation dose in the environment. Decontamination work in the contaminated area except a mountain forests has been conducted to decrease the radiation dose. However, there are concerns that the redistribution of this radiation due to water discharge will occur due to the resulting transport of radiocesium. In particular, the deposition of soil particles containing radiocesium on the flood plains in the downstream areas of Fukushima's rivers can potentially increase the local radiation dose. Therefore, it is important to understand the influence of the deposition behavior of radiocesium on the radiation dose. Investigations of rivers have been performed to enhance the understanding of the mechanisms by which radiocesium is deposited on these flood plains. It was found that the spatial distribution of the radiocesium concentration on the flood plain along the river is heterogeneous with a dependence on the depositional condition and that the number of points with high air dose rates is limited. In detail, the radiocesium concentration and air dose rates in flood channels are higher than those at the edges of the river channels. Based on these heterogeneity and hydrological events, the deposition and transport mechanisms of the radiocesium due to water discharge at rivers were also interpreted, and a conceptual model was constructed. PMID- 27414487 TI - Inflammation, vitamin D and dendritic cell precursors in chronic kidney disease. AB - Decreased blood dendritic cell precursors (DCP) count is linked with atherosclerotic disease, while reduction of circulating DCP is also seen in patients with chronic kidney disease (CKD). As poor vitamin D status could be linked to a compromised innate immune response, we hypothesized that vitamin D status might be involved in the decrease in circulating DCP in CKD. Moreover, the potential role of inflammation was considered. Circulating myeloid (mDCP), plasmacytoid (pDCP) and total DCP (tDCP) were analysed using flow cytometry in 287 patients with CKD stage 3. Serum 25(OH)D and 1,25(OH)2D levels were measured using enzyme-linked immunosorbent assays (ELISA), interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-alpha using cytometric bead array, C-reactive protein (CRP) using a high-sensitivity (hs) ELISA. Contrary to our hypothesis, there was no association between vitamin D levels and DCP, although their number was decreased significantly in CKD (P < 0.001). Instead, mDCP (r = -0.211) and tDCP (r = -0.188,) were associated slightly negatively with hsCRP but positively with the estimated glomerular filtration rate (eGFR, r = 0.314 for tDCP). According to multivariate linear regression, only higher hsCRP concentration and the presence of diabetes mellitus had a significant negative influence on DCP count (P < 0.03, respectively) but not vitamin D, age and eGFR. A significant impact of vitamin D on the reduction of circulating DCP in CKD 3 patients can be neglected. Instead, inflammation as a common phenomenon in CKD and diabetes mellitus had the main influence on the decrease in DCP. Thus, a potential role for DCP as a sensitive marker of inflammation and cardiovascular risk should be elucidated in future studies. PMID- 27414489 TI - Activation of Elemental Sulfur at a Two-Coordinate Platinum(0) Center. AB - Platinum dichalcogenides have been known to exhibit two-dimensional layered structures. Herein, we describe the syntheses, isolation, and characterization of air-stable crystalline cyclic alkyl(amino) carbene (cAAC)-supported monomeric platinum disulfide three-membered ring complex [(cAAC)2 Pt(S2 )] (2). The highly reactive platinum(0) [(cAAC)2 Pt] complex (1) with two-coordinate platinum activates elemental sulfur to give 2. The brown crystals of bis-carbene platinum(II)monosulfate [(cAAC)2 Pt(SO4 )x (S2 )1-x ] (4) have been isolated when the reaction was performed in air. The dioxygen analogue of 2 was formed upon exposing the THF solution of 1 to aerial oxygen (O2 ). The binding of oxygen at the Pt(0) center was found to be reversible. Additionally, DFT study has been performed to elucidate the electronic structure and bonding scenario of 2, 3, and 4. Quantum chemical calculations showed donor-acceptor-type interaction for the Pt-S bonds in 2 and Pt-O bonds in 3 and 4. PMID- 27414490 TI - 3D helical and 2D rhomboidal supramolecules: stepwise self-assembly and dynamic transformation of terpyridine-based metallo-architectures. AB - A Ru(2+)-connected, metallo-organic ligand (L) with three free terpyridines was designed and synthesized. L was assembled with Zn(2+) to generate a helical structure; however, when mixing L with a 1,2,3-tristerpyridine ligand (T), a thermodynamically stable 2D rhombus was assembled. Furthermore, this 2D rhomboidal structure can also be achieved through the dynamic transformation of preassembled helix H with T and Zn(2+) at room temperature. PMID- 27414491 TI - Variable bleeding phenotype in an Amish pedigree with von Willebrand disease. AB - Through a cross-sectional study design, the bleeding phenotype in the Amish in Indiana (IN) and Wisconsin (WI) was described using two different bleeding scores. von Willebrand factor (VWF) testing was performed and bleeding questionnaires from Centers for Disease Control and Prevention (CDC) and European MCMDM-1 (Tosetto bleeding score (BS)) were administered to the IN and WI cohort respectively. Seven hundred and seventy nine subjects were recruited, 17% were diagnosed with VWD based on Ristocetin cofactor, VWF:RCo < 30 IU/dl. Majority of the affected (AF), 67%, were tested and had a common mutation c.4120 C > T. The WI AF were much younger at a mean age 15 years vs 26 years in IN AF cohort. The AF subjects had a median VWF:RCo of 13IU/dl with a statistically significant higher median BS 1 versus 0 in the WI AF vs WI Unaffected (UA), 2 vs 1 in the IN AF vs IN UA, P < 0.01. Adults had a higher median BS compared to children in the WI and IN cohort, 2 vs 1 and 3 vs 1 respectively (P < 0.05) but there was no statistically significant difference in the BS between males and females in either cohort. The common symptoms reported were epistaxis and gingival oozing. BS >= 3 and BS >= 4 were observed in 46% of AF IN and 16.6% of AF WI, respectively. There was significant variability in the bleeding phenotype, with an overall low BS in the affected Amish with VWD, despite a unifying mutation. Am. J. Hematol. 91:E431-E435, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27414492 TI - Fast-Track Clearance of Bacteria from the Liver. AB - The liver plays a central role in clearing bacteria from the bloodstream. Two articles in this issue of Cell Host & Microbe (Broadley et al., 2016; Zeng et al., 2016) identify new mechanisms by which resident liver macrophages (Kupffer cells) rapidly capture bacteria from the blood and eliminate them, while still allowing for the induction of adaptive immunity. PMID- 27414493 TI - Ticks Take Cues from Mammalian Interferon. AB - Interferons are considered a first line of immune defense restricted to vertebrates. In this issue of Cell Host & Microbe, Smith et al. (2016) demonstrate that mammalian interferon gamma activates an antimicrobial response within ticks feeding on blood. The study suggests that arthropods have a parallel interferon-like defense system. PMID- 27414494 TI - Flying Under the Radar: Immune Evasion by Group B Streptococcus. AB - Type I IFN production is an important host defense mechanism against Gram positive Streptococci. In this issue of Cell Host & Microbe, Andrade et al. (2016) report that Group B Streptococcus limits type I IFN by expressing a surface phosphodiesterase that degrades extracellular bacterial cyclic dinucleotides, thereby promoting virulence. PMID- 27414495 TI - Tummy Time: The Infant Microbiota-IgA Connection. AB - Dirty diapers do not often come to mind when thinking about cutting-edge biomedical research. However, in a recent Nature paper, Planer et al. (2016) report results from a longitudinal study examining gut microbiota maturation and corresponding intestinal immune responses in healthy twin pairs over the first 3 years of life. PMID- 27414496 TI - Placental Mechanics in the Zika-Microcephaly Relationship. AB - How the Zika virus (ZIKV) accesses the embryo remains unknown. In this issue, Quicke et al. (2016) use an in vitro model of the human placenta to show that placental macrophages are more permissive to ZIKV infection than trophoblasts, which may be refractory to infection (Bayer et al., 2016). PMID- 27414499 TI - A Systems Survey of Progressive Host-Cell Reorganization during Rotavirus Infection. AB - Pathogen invasion is often accompanied by widespread alterations in cellular physiology, which reflects the hijacking of host factors and processes for pathogen entry and replication. Although genetic perturbation screens have revealed the complexity of host factors involved for numerous pathogens, it has remained challenging to temporally define the progression of events in host cell reorganization during infection. We combine high-confidence genome-scale RNAi screening of host factors required for rotavirus infection in human intestinal cells with an innovative approach to infer the trajectory of virus infection from fixed cell populations. This approach reveals a comprehensive network of host cellular processes involved in rotavirus infection and implicates AMPK in initiating the development of a rotavirus-permissive environment. Our work provides a powerful approach that can be generalized to order complex host cellular requirements along a trajectory of cellular reorganization during pathogen invasion. PMID- 27414497 TI - Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production. AB - Induction of type I interferon (IFN) in response to microbial pathogens depends on a conserved cGAS-STING signaling pathway. The presence of DNA in the cytoplasm activates cGAS, while STING is activated by cyclic dinucleotides (cdNs) produced by cGAS or from bacterial origins. Here, we show that Group B Streptococcus (GBS) induces IFN-beta production almost exclusively through cGAS-STING-dependent recognition of bacterial DNA. However, we find that GBS expresses an ectonucleotidase, CdnP, which hydrolyzes extracellular bacterial cyclic-di-AMP. Inactivation of CdnP leads to c-di-AMP accumulation outside the bacteria and increased IFN-beta production. Higher IFN-beta levels in vivo increase GBS killing by the host. The IFN-beta overproduction observed in the absence of CdnP is due to the cumulative effect of DNA sensing by cGAS and STING-dependent sensing of c-di-AMP. These findings describe the importance of a bacterial c-di AMP ectonucleotidase and suggest a direct bacterial mechanism that dampens activation of the cGAS-STING axis. PMID- 27414498 TI - Toxoplasma Effector Recruits the Mi-2/NuRD Complex to Repress STAT1 Transcription and Block IFN-gamma-Dependent Gene Expression. AB - Interferon gamma (IFN-gamma) is an essential mediator of host defense against intracellular pathogens, including the protozoan parasite Toxoplasma gondii. However, prior T. gondii infection blocks IFN-gamma-dependent gene transcription, despite the downstream transcriptional activator STAT1 being activated and bound to cognate nuclear promoters. We identify the parasite effector that blocks STAT1 dependent transcription and show it is associated with recruitment of the Mi-2 nucleosome remodeling and deacetylase (NuRD) complex, a chromatin-modifying repressor. This secreted effector, toxoplasma inhibitor of STAT1-dependent transcription (TgIST), translocates to the host cell nucleus, where it recruits Mi-2/NuRD to STAT1-dependent promoters, resulting in altered chromatin and blocked transcription. TgIST is conserved across strains, underlying their shared ability to block IFN-gamma-dependent transcription. TgIST deletion results in increased parasite clearance in IFN-gamma-activated cells and reduced mouse virulence, which is restored in IFN-gamma-receptor-deficient mice. These findings demonstrate the importance of both IFN-gamma responses and the ability of pathogens to counteract these defenses. PMID- 27414500 TI - Highly sensitive and reproducible silicon-based surface-enhanced Raman scattering sensors for real applications. AB - During the past few decades, thanks to silicon nanomaterials' outstanding electronic/optical/mechanical properties, large surface-to-volume ratio, abundant surface chemistry, facile tailorability and good compatibility with modern semiconductor industry, different dimensional silicon nanostructures have been widely employed for rationally designing and fabricating high-performance surface enhanced Raman scattering (SERS) sensors for the detection of various chemical and biological species. Among these, two-dimensional silicon nanostructures made of metal nanoparticle-modified silicon wafers and three-dimensional silicon nanostructures made of metal nanoparticle-decorated SiNW arrays are of particular interest, and have been extensively exploited as promising silicon-based SERS active substrates for the construction of high-performance SERS sensors. With an aim to retrospect these important and exciting achievements, we herein focus on reviewing recent representative studies on silicon-based SERS sensors for sensing applications from a broad perspective and possible future direction, promoting readers' awareness of these novel powerful silicon-based SERS sensing technologies. Firstly, we summarize the two unique merits of silicon-based SERS sensors, and those are high sensitivity and good reproducibility. Next, we present recent advances of two- and three-dimensional silicon-based SERS sensors, especially for real applications. Finally, we discuss the major challenges and prospects for the development of silicon-based SERS sensors. PMID- 27414501 TI - A Dual-Catalytic Strategy To Direct Asymmetric Radical Aminotrifluoromethylation of Alkenes. AB - A novel asymmetric radical aminotrifluoromethylation of alkenes has been developed for the first time, providing straightforward access to densely functionalized CF3-containing azaheterocycles bearing an alpha-tertiary stereocenter with excellent enantioselectivity. The key to success is not only the introduction of a Cu(I)/chiral phosphoric acid dual-catalytic system but also the use of urea with two acidic N-H as both the nucleophile and directing group. The utility of this method is illustrated by facile transformations of the products into other important compounds useful in organic synthesis and medicinal chemistry. PMID- 27414502 TI - Cation-Induced Hydration Effects Cause Lower Critical Solution Temperature Behavior in Protein Solutions. AB - The phase behavior of protein solutions is important for numerous phenomena in biology and soft matter. We report a lower critical solution temperature (LCST) phase behavior of aqueous solutions of a globular protein induced by multivalent metal ions around physiological temperatures. The LCST behavior manifests itself via a liquid-liquid phase separation of the protein-salt solution upon heating. Isothermal titration calorimetry and zeta-potential measurements indicate that here cation-protein binding is an endothermic, entropy-driven process. We offer a mechanistic explanation of the LCST. First, cations bind to protein surface groups driven by entropy changes of hydration water. Second, the bound cations bridge to other protein molecules, inducing an entropy-driven attraction causing the LCST. Our findings have general implications for condensation, LCST, and hydration behavior of (bio)polymer solutions as well as the understanding of biological effects of (heavy) metal ions and their hydration. PMID- 27414503 TI - Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance - The Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014. AB - PROBLEM/CONDITION: Gonorrhea is the second most commonly reported notifiable disease in the United States; 350,062 gonorrhea cases were reported in 2014. Sexually transmitted infections caused by Neisseria gonorrhoeae are a cause of pelvic inflammatory disease in women, which can lead to serious reproductive complications including tubal infertility, ectopic pregnancy, and chronic pelvic pain. Prevention of sequelae and of transmission to sexual partners relies largely on prompt detection and effective antimicrobial treatment. However, treatment has been compromised by the absence of routine antimicrobial susceptibility testing in clinical care and evolution of antimicrobial resistance to the antibiotics used to treat gonorrhea. PERIOD COVERED: 2014. DESCRIPTION OF THE SYSTEM: The Gonococcal Isolate Surveillance Project (GISP) was established in 1986 as a sentinel surveillance system to monitor trends in antimicrobial susceptibilities of N. gonorrhoeae strains in the United States. Each month, N. gonorrhoeae isolates are collected from up to the first 25 men with gonococcal urethritis attending each of the participating sexually transmitted disease (STD) clinics at 27 sites. The number of participating sites has varied over time (21 30 per year). Selected demographic and clinical data are abstracted from medical records. Isolates are tested for antimicrobial susceptibility using agar dilution at one of five regional laboratories. RESULTS: A total of 5,093 isolates were collected in 2014. Of these, 25.3% were resistant to tetracycline, 19.2% to ciprofloxacin, and 16.2% to penicillin (plasmid-based, chromosomal, or both). Reduced azithromycin susceptibility (Azi-RS) (defined as minimum inhibitory concentration [MIC] >=2.0 ug/mL) increased from 0.6% in 2013 to 2.5% in 2014. The increase occurred in all geographic regions, but was greatest in the Midwest, and among all categories of sex of sex partners (men who have sex with men [MSM], men who have sex with men and women [MSMW], and men who have sex with women [MSW]). No Azi-RS isolates exhibited reduced cefixime or ceftriaxone susceptibility (Cfx RS and Cro-RS, respectively). The prevalence of Cfx-RS (MIC >=0.25 ug/mL) increased from 0.1% in 2006 to 1.4% in both 2010 and 2011, decreased to 0.4% in 2013, and increased to 0.8% in 2014. Cro-RS (MIC >=0.125 ug/mL) increased following a similar pattern but at lesser percentages (increased from 0.1% in 2008 to 0.4% in 2011 and decreased to 0.1% in 2013 and 2014). The percentage of isolates resistant to tetracycline, ciprofloxacin, penicillin, or all three antimicrobials, was greater in isolates from MSM than from MSW. INTERPRETATION: This is the first report to present comprehensive surveillance data from GISP and summarize gonococcal susceptibility over time, as well as underscore the history and public health implications of emerging cephalosporin resistance. Antimicrobial susceptibility patterns vary by geographic region within the United States and by sex of sex partner. Because dual therapy with ceftriaxone plus azithromycin is the only recommended gonorrhea treatment, increases in azithromycin and cephalosporin MICs are cause for concern that resistance to these antimicrobial agents might be emerging. It is unclear whether increases in the percentage of isolates with Azi-RS mark the beginning of a trend. The percentage of isolates with elevated cefixime MICs increased during 2009-2010, then decreased during 2012-2013 after treatment recommendations were changed in 2010 to recommend dual therapy (with a cephalosporin and a second antibiotic) and a higher dosage of ceftriaxone. Subsequently, the treatment recommendations were changed again in 2012 to no longer recommend cefixime as part of first-line therapy (leaving ceftriaxone-based dual therapy as the only recommended therapy). Despite the MIC decrease (i.e., trend of improved cefixime susceptibility) during 2012-2013, the increase in the number of strains with Cfx-RS in 2014 underscores the potential threat of cephalosporin-resistant N. gonorrhoeae. PUBLIC HEALTH ACTION: The National Strategy for Combating Antibiotic-Resistant Bacteria identifies prevention, rapid detection, and control of outbreaks of ceftriaxone resistant N. gonorrhoeae infection as a priority for U.S. PUBLIC HEALTH ACTION: Antimicrobial susceptibility surveillance is conducted to guide development of treatment recommendations for effective therapy and prevention of complications from and transmission of gonorrhea. Federal agencies can use GISP data to develop national treatment recommendations and set research and prevention priorities. Local and state health departments can use GISP data to determine allocation of STD prevention services and resources, guide prevention planning, and communicate best treatment practices to health care providers. Continued surveillance, appropriate treatment, development of new antibiotics, and prevention of transmission remain the best strategies to reduce gonorrhea incidence and morbidity. PMID- 27414505 TI - Simon Wolff. PMID- 27414504 TI - Temperature-Triggered Dielectric-Optical Duple Switch Based on an Organic Inorganic Hybrid Phase Transition Crystal: [C5N2H16]2SbBr5. AB - Molecular optical-electrical duple switches (switch "ON" and "OFF" bistable states) represent a class of highly desirable intelligent materials because of their sensitive switchable physical and/or chemical responses, simple and environmentally friendly processing, light weights, and mechanical flexibility. In the current work, the phase transition of 1 (general formula R2MX5, [C5N2H16]2[SbBr5]) can be triggered by the order-disorder transition of the organic cations at 278.3 K. The temperature-induced phase transition causes novel bistable optical-electrical duple characteristics, which indicates that 1 might be an excellent candidate for a potential switchable optical-electrical (fluorescence/dielectric) material. In the dielectric measurements, remarkable bistable dielectric responses were detected, accompanied by striking anisotropy along various crystallographic axes. For the intriguing fluorescence emission spectra, the intensity and position changed significantly with the occurrence of the structural phase transition. We believe that these findings might further promote the application of halogenoantimonates(III) and halogenobismuthates(III) in the field of optoelectronic multifunctional devices. PMID- 27414506 TI - Is research quality quality research? PMID- 27414507 TI - The assessment of protein glycation in human atherosclerotic plaques by affinity chromatography. AB - Human atherosclerotic plaques are characterized by a massive deposition of lipid within arterial walls. The lipids accumulated are partly oxidized, as assessed by gas chromatography of lipids and their oxidation products. Both advancing age and diabetes mellitus are associated with an increased prevalence and severity of atherosclerosis. In diabetes mellitus the development of secondary complications appear to be increased by poor glucose control. Indeed, the post-translational modification of protein by non-enzymatic glycation may provide the link between abnormal glucose control and diabetic complications. For atherosclerosis however, the relationship between glucose control and disease is unclear, with evidence available to support and discount such a link. To study protein glycation in a condition associated with a significant level of lipid oxidation products poses several methodological problems, most of which are associated with interference by lipid-derived aldehydes. Many chemical assays of protein glycation monitor aldehydic products common to the chemistry of both protein glycation and lipid oxidation. Studies of protein glycation in human atheroma, obtained at necropsy, are presented which make use of a commercially available boronic acid affinity based chromatographic assay of glycated protein. The commercially available affinity-based chromatographic assay of glycated protein appears to be free from such interference and may well prove useful in the study of other conditions in which the non-enzymatic glycation of protein is suspected. PMID- 27414508 TI - Macrophage erythrophagocytosis and iron exocytosis. AB - Senescent, or damaged, erythrocytes are removed from the blood stream mainly by the macrophage system. Such cells may acquire and store large quantities of the redox-active transition metal iron that, if released together with superoxide and hydrogen peroxide during an oxidative burst, may induce peroxidative reactions with a variety of surrounding substances, e.g., low-density lipoprotein (LDL). In this study we demonstrate 1. the temporary sequestration of iron within the secondary lysosomal apparatus of both established macrophage-like J-774 cells and human monocyte-derived macrophages secondary to the uptake and degradation of native and photo-oxidized (ultraviolet UV light) erythrocytes; and 2. an ensuing development by these cells of a capacity for iron-exocytosis. The binding and uptake by human macrophages and J-774 cells of artificially aged, UV-irradiated erythrocytes were stimulated compared to that of native erythrocytes. The uptake resulted in lysosomal accumulation of iron in a low-molecular weight form, as shown by autometallography. Cells exposed to ferric chloride were used as positive controls. Ensuing exocytosis of iron to the culture medium was demonstrated by atomic absorption spectroscopy. Our findings suggest that macrophage erythrophagocytosis is a useful model for the study of the sequestration of iron within the macrophage acidic vacuolar apparatus, its subsequent exocytosis, and oxidative effect on extracellular LDL. PMID- 27414509 TI - Studies on paraquat toxicity on deoxyribonucleic acid of cultured mammalian cells using flow cytometry. AB - The beginning of the cell death process initiated by paraquat is caused by oxygen free radicals produced through the redox cycle. We examined the next step driven by the radicals focusing on changes in deoxyribonucleic acid (DNA) utilizing flow cytometry. A significant decrease in the proportion of cells was observed in the G0/G1 phase, while a remarkable accumulation of cells was noted in the S phase. Forward light scattering (FSC) and side light scattering (SSC) histograms of the particles from cells treated with paraquat showed a change in the size, the refractive index and the granularity of the nucleoids. By contrast, leakage of lactate dehydrogenase (LDH) was not observed during the period in which changes in DNA occurred. These results suggest that paraquat-induced DNA damage constitutes one of the next steps driven by free radicals, leading to the process of cell death. PMID- 27414510 TI - Analysis of native and oxidized low-density lipoprotein oxysterols using gas chromatography-mass spectrometry with selective ion monitoring. AB - Cholesterol oxidation products have been demonstrated to possess a wide variety of biological properties and have been implicated in playing an important role in the development of atherosclerosis. We have developed an analytical method using capillary gas chromatography-mass spectrometry (GC-MS) for the analysis of cholesterol oxidation products in low-density lipoprotein (LDL). The method uses programmed multiple selected ion monitoring (SIM), providing enhanced sensitivity and accuracy of peak detection over full-scan mass spectra. The major oxidation products of cholesterol in oxidized LDL were identified as 7beta-hydroxy cholesterol and 7-keto-cholesterol. Minor products included 4beta-hydroxy cholesterol, 6beta-hydroxy-cholesterol and cholesterol-5alpha,6alpha-epoxide. Native LDL contains 7-lathosterol, which is a biosynthetic precursor of cholesterol, as well as low levels of 7beta-hydroxy-cholesterol and 7-keto cholesterol. 7-Lathosterol was not detected in oxidized LDL. A time course oxidation of native LDL with 8 MUM CuCl2 demonstrated a rapid increase in 7beta hydroxy-cholesterol and 7-keto-cholesterol over the first 4 h. Cholesterol 5alpha,6alpha-epoxide, and beta4-hydroxy- and 6beta-hydroxy-cholesterol levels increased gradually, while 7-lathosterol decreased over the same period. This method was used to measure the levels of 7-lathosterol and cholesterol oxides in the LDL of 20 healthy subjects in order to establish the mean concentration and a reference range. This method can be used for the characterization and quantitation of oxysterols in native and oxidized LDL and may afford an additional index of oxidative modification of plasma lipoproteins. PMID- 27414511 TI - Differing features of proteins in membranes may result in antioxidant or prooxidant action: opposite effects on lipid peroxidation of alcohol dehydrogenase and albumin in liposomal systems. AB - The influence of 3 thiol-containing compounds, bovine serum albumin (fatty acid free: BSA), glutathione (GSH) and yeast alcohol dehydrogenase (YADH) on lipid peroxidation in multilamellar liposomes, prepared from ox-brain phospholipid, was investigated. Thiol-compounds were added either before liposome formation, or after liposome formation; and their effects compared to a positive control. Bovine serum albumin (BSA), an acidic hydrophilic protein, displays a small, concentration dependent, antioxidant effect when added to preformed liposomes. A much larger antioxidant effect was observed when the BSA was entrapped inside the liposome, by adding BSA just prior to liposome preparation. In contrast, a Zn(2+) containing redox enzyme, YADH, a basic hydrophobic membrane-associating protein, displays a large pro-oxidant effect at much lower concentrations especially when entrapped inside the liposome. This was observed also with GSH; but per mole of SH, YADH was about 18 times as powerful a pro-oxidant perhaps because of structural changes to the membrane. Oxidized glutathione and N-acetylcysteine were also pro-oxidant (cysteine and cystine showed little effect). Formation of thiyl radicals may occur in the presence of iron ions with these pro-oxidant sulphur-containing compounds. Partial protection against lipid peroxidation was observed with EDTA, desferrioxamine and protoporphyrin (IX), potent iron chelating agents. PMID- 27414512 TI - Iron mobilization from ultraviolet-irradiated, iron-saturated, transferrin. AB - Transferrin is the major iron transport protein of mammalian plasma. The ultraviolet-B irradiation of 1.4 mg/ml iron saturated transferrin solutions (~32 MUM Fe(3+)) induces a Fe(3+) loss accompanied by Fe(2+) formation. The initial quantum yield of Fe(3+) loss is wavelength dependent (phi(313 nm)~1.3*10(-3)) and oxygen independent suggesting an intramolecular electron transfer from one of the Fe(3+) ligands. A photolysis of tryptophan residues parallels this photoreduction. PMID- 27414513 TI - Tryptophan reaction with free radicals arisen from carbon tetrachloride in a model system. A mass spectrometric study. AB - The interaction between free radicals derived from the thermal decomposition of carbon tetrachloride and N-acetyl-d, l-tryptophan ethyl ester (TRPAE) under anaerobic and aerobic conditions was studied. The structure of the reaction products formed was deciphered by the GC/MS analysis of their trimethylsilyl derivatives. Under anaerobic conditions no formation of reaction products was detected. Under aerobic conditions the following products were identified: 1. A chloro hydroxy unsaturated adduct of TRPAE (2 isomers). 2. A dichloro hydroxy unsaturated adduct of TRPAE. 3. 12 products which are different pyrrolo[2,3 b]indol derivatives. Some of the products appeared to have an hydroxyl group as a substituent, all of them contained chlorine and only one contained carbon from CCl4. Interestingly, the formation of those adducts not containing CCl3 would be missed during the regular procedures toxicologists use to determine the so-called 'covalent binding' employing (14)CCl4. Concerning the potential relevance of these findings, we hypothesize that if interactions similar to those here reported occurred at least in part during CCl4 poisoning, the resulting critical proteins containing tryptophan, e.g. membrane or other and enzymes containing the amino acid in their active center, might be impaired. PMID- 27414514 TI - Reduction of ubiquinone-1 by ascorbic acid is a catalytic and reversible process controlled by the concentration of molecular oxygen. AB - To address whether reduction by vitamin C may contribute to the in vivo maintenance of coenzyme Q in the reduced form, we studied the reduction of ubiquinone-1 by ascorbate at pH 7.4. Addition of ascorbate to ubiquinone-1 resulted in rapid O2 consumption and an increase in the steady-state concentration of ascorbyl radical. The initial rate of O2 consumption was proportional to the product of [ubiquinone-1] and [ascorbate] whereas [ascorbyl radical] was proportional to the square root of this parameter; both dependencies were in quantitative agreement with each other. The extent of O2 consumption greatly exceeded the amounts of ubiquinone-1 initially present. Formation of ubiquinol-1 from ubiquinone-1 by ascorbate was reversible, moderate under aerobic conditions, but substantial in the absence or near absence of oxygen. At high O2 concentration, ascorbate promoted the oxidation of ubiquinol-1 to ubiquinone-1. Addition of sodium dodecyl sulphate dramatically decreased the rate of reaction between ubiquinone-1 and ascorbate, most likely as a result of phase separation of the reagents. A preliminary reaction scheme with putative rate constants for the relevant reactions is presented that quantitatively describes the kinetic behaviour of the process studied. The key reactions in the scheme are electron transfer from ascorbate to ubiquinone-1 with formation of the ascorbyl and ubisemiquinone radical. The reaction of the latter with O2 is postulated to be responsible for O2 consumption, with ubiquinone-1 acting as a catalyst. Together, the results demonstrate that the extent of reduction of ubiquinone-1 by ascorbate was controlled by the O2 concentration and the physical availability of the reactants. As the O2 concentration in human blood is relatively high and ubiquinone-10 is located exclusively within the lipid phase of lipoproteins where negatively charged ascorbate has little access, our results suggest that direct reduction by ascorbate is unlikely to be responsible for the high reduction percentage observed for plasma coenzyme Q. PMID- 27414515 TI - Direct determination of diene conjugation and deoxyribonucleic acid (DNA) oxidative damage can explain the role of DTPA-Fe(2+)-O2 complex in a linoleic acid-DNA system. AB - Exposure of linoleic acid to diethylenetriminepentaacetic acid (DTPA)-Fe(2+) complexes resulted in fast diene conjugation and peroxidized products which could further react with deoxyribonucleic acid (DNA) to cause DNA oxidative damage. In this paper, we have detected diene conjugation and DNA oxidative damage in a linoleic acid-DNA model system driven by DTPA-Fe(2+) and found that: 1. in air or oxygen-saturated reaction systems, addition of hydrogen peroxide resulted in a decrease in diene conjugation and double-stranded DNA content, but had no obvious effects on the formation of DNA fluorescent products; 2. in anoxic conditions, addition of hydrogen peroxide had no effect on the formation of diene conjugation and fluorescent products, but resulted in a decrease of double-stranded DNA content; 3. in the presence of DTPA, Fe(3+) did not stimulate the formation of diene conjugation; 4. the formation of diene conjugation and fluorescent products was not inhibited by superoxide dismutase, catalase, sodium benzoate, sodium azide and mannitol. However, these 'scavengers' increased the percentage of double-strand DNA to different degrees. alpha-tocopherol, but not reduced glutathione (GSH), inhibited the formation of diene conjugates. alpha-tocopherol and GSH both could reduce the amounts of fluorescent products and DNA strand breaks. Taken together, these data further indicate that chelator-Fe(2+)-O2 complex, a perferryl-type oxidant, is probably an important initiator of lipid peroxidation in the linoleic acid-DNA system. PMID- 27414516 TI - Hydroxyl radical production by the iron complex of the hydrolysis product of the antioxidant cardioprotective agent ICRF-187 (dexrazoxane). AB - Dexrazoxane (ICRF-187) is now in clinical use for the prevention of doxorubicin induced cardiotoxicity. This cardiotoxicity is thought to be due to iron-mediated oxidative stress. Dexrazoxane may be acting through its strongly metal ion binding rings-opened hydrolysis product ADR-925 by complexing iron. Since iron chelates are known to be able to produce hydroxyl radicals, an electron paramagnetic resonance spin trapping study was undertaken to compare the hydroxyl radical-producing ability of the ferrous-ADR-925 complex with that of the ferrous complexes of ethylenediaminetetraacetic acid (EDTA) and the tetraacid analog of ADR-925 (DAPTA). In spectrophotometric studies it was shown that the ferrous-ADR 925 complex underwent aerobic oxidation 87 and 44 times slower than the ferrous complexes of EDTA or 1,2-diaminopropane-N,N,N',N'-tetraacetic acid (DAPTA), respectively. In spite of the much slower oxidation of the ferrous-ADR-925 complex, it was, nonetheless, equally effective in producing hydrogen peroxide dependent spin adducts. These spin adducts were produced from the reaction of the spin trap with free hydroxyl radical (HO(.)), and with a transient iron oxidant with HO(.)-like reactivity. Thus, it is concluded that ADR-925 acts by either complexing free iron or iron bound to doxorubicin, and forming a soluble iron complex that is less effective at producing site-specific oxygen radical damage. PMID- 27414517 TI - The omega-3 fatty acid peroxidation paradox. PMID- 27414519 TI - Survivorship in Head and Neck Cancer: A Primer. AB - Survivors of cancer and cancer-directed therapies may encounter substantial medical, psychosocial, interpersonal, financial, and functional consequences. The collective experience of being a cancer survivor has been dubbed survivorship. As a unique discipline, cancer survivorship has garnered much attention in recent years. However, its constructs have yet to be formally introduced or applied to head and neck oncology. Recognizing this, the American Head and Neck Society (AHNS) has convened a committee on survivorship. The concept of survivorship is reviewed and placed into historical perspective to identify current gaps in head and neck survivor care and to provide a roadmap for future initiatives in survivorship care and research. PMID- 27414518 TI - Epitaxy of GaN Nanowires on Graphene. AB - Epitaxial growth of GaN nanowires on graphene is demonstrated using molecular beam epitaxy without any catalyst or intermediate layer. Growth is highly selective with respect to silica on which the graphene flakes, grown by chemical vapor deposition, are transferred. The nanowires grow vertically along their c axis and we observe a unique epitaxial relationship with the ?2110? directions of the wurtzite GaN lattice parallel to the directions of the carbon zigzag chains. Remarkably, the nanowire density and height decrease with increasing number of graphene layers underneath. We attribute this effect to strain and we propose a model for the nanowire density variation. The GaN nanowires are defect-free and they present good optical properties. This demonstrates that graphene layers transferred on amorphous carrier substrates is a promising alternative to bulk crystalline substrates for the epitaxial growth of high quality GaN nanostructures. PMID- 27414520 TI - Electrochemical Detection of Amyloid-beta Oligomers Based on the Signal Amplification of a Network of Silver Nanoparticles. AB - Amyloid-beta oligomers (AbetaOs) are the most important toxic species in the brain of Alzheimer's disease (AD) patient. AbetaOs, therefore, are considered reliable molecular biomarkers for the diagnosis of AD. Herein, we reported a simple and sensitive electrochemical method for the selective detection of AbetaOs using silver nanoparticles (AgNPs) as the redox reporters and PrP(95 110), an AbetaOs-specific binding peptide, as the receptor. Specifically, adamantine (Ad)-labeled PrP(95-110), denoted as Ad-PrP(95-110), induced the aggregation and color change of AgNPs and the follow-up formation of a network of Ad-PrP(95-110)-AgNPs. Then, Ad-PrP(95-110)-AgNPs were anchored onto a beta cyclodextrin (beta-CD)-covered electrode surface through the host-guest interaction between Ad and beta-CD, thus producing an amplified electrochemical signal through the solid-state Ag/AgCl reaction by the AgNPs. In the presence of AbetaOs, Ad-PrP(95-110) interacted specifically with the AbetaOs, thus losing the capability to bind AgNPs and to induce the formation of an AgNPs-based network on the electrode surface. Consequently, the electrochemical signal decreased with an increase in the concentration of AbetaOs in the range of 20 pM to 100 nM. The biosensor had a detection limit of 8 pM and showed no response to amyloid-beta monomers (AbetaMs) and fibrils (AbetaFs). On the basis of the well-defined and amplified electrochemical signal of the AgNPs-based network architecture, these results should be valuable for the design of novel electrochemical biosensors by marrying specific receptors. PMID- 27414522 TI - Bleak new year ahead. AB - Out with the old and in with the new at least that's how the old adage goes, unfortunately for nurses 1988 is likely to bring more of the same. Nursing has rarely seemed less attractive as a profession. PMID- 27414523 TI - Report calls for organ transplant updates. AB - Every general hospital should have a transplant study day to update nurses on organ transplant and donation, according to a report from the Medical Royal Colleges. PMID- 27414521 TI - The Human Skeletal Muscle Transcriptome in Response to Oral Shilajit Supplementation. AB - The objective of the present study ( clinicaltrials.gov NCT02026414) was to observe the effects of oral supplementation of a purified and standardized Shilajit extract on skeletal muscle adaptation in adult overweight/class I obese human subjects from the U.S. POPULATION: Shilajit is a mineral pitch that oozes out of Himalayan rocks. The study design consisted of a baseline visit, followed by 8 weeks of 250 mg of oral Shilajit supplementation b.i.d., and additional 4 weeks of supplementation with exercise. At each visit, blood samples and muscle biopsies were collected for further analysis. Supplementation was well tolerated without any changes in blood glucose levels and lipid profile after 8 weeks of oral supplementation and the additional 4 weeks of oral supplementation with exercise. In addition, no changes were noted in creatine kinase and serum myoglobin levels after 8 weeks of oral supplementation and the additional 4 weeks of supplementation with exercise. Microarray analysis identified a cluster of 17 extracellular matrix (ECM)-related probe sets that were significantly upregulated in muscles following 8 weeks of oral supplementation compared with the expression at the baseline visit. This cluster included tenascin XB, decorin, myoferlin, collagen, elastin, fibrillin 1, and fibronectin 1. The differential expression of these genes was confirmed using quantitative real-time polymerase chain reaction (RT-PCR). The study provided maiden evidence that oral Shilajit supplementation in adult overweight/class I obese human subjects promoted skeletal muscle adaptation through upregulation of ECM-related genes that control muscle mechanotransduction properties, elasticity, repair, and regeneration. PMID- 27414524 TI - First regional nurse adviser for Macmillan services appointed. AB - Wessex Regional Health Authority last week appointed the first Regional Nurse Adviser for Macmillan Services. PMID- 27414526 TI - Aids fellowship awarded. AB - A London midwife has been awarded L3,000 to study [illegible word] nursing needs of pregnant women who are HIV positive. PMID- 27414525 TI - Concern over weaning foods. AB - Health visitors are concerned that distributing 'bounty cards' - vouchers for free samples of weaning foods - to mothers may conflict with their role as independent health advisers. PMID- 27414527 TI - Report stresses care on low calorie diets. AB - Very low calorie diets (VLCD) should not be used by the very old, the very young, or pregnant and breast feeding women, according to a Government backed report. Anybody thinking of using the diets should consult their doctor first. PMID- 27414529 TI - Poor treatment during scans raises anxiety. AB - Anxiety levels experienced by women who are scanned for abnormalities during pregnancy are heightened if they are poorly treated during the procedure, according to psychologists from the Royal Free Hospital in London. PMID- 27414530 TI - Scholarship awarded for study into allergic conditions in children. AB - A health visitor from Lincolnshire has won a L1,000 scholarship to study the incidence and possible causes of allergic conditions in children under a year. PMID- 27414532 TI - US scholarship to study computers. AB - A nurse from Wales has won a L3,500 scholarship to visit North America and look at the use of computers in the nursing process. PMID- 27414533 TI - New vaccine approved. AB - The one dose, combined vaccination against measles, mumps and rubella (MMR) has finally been cleared for use by the Department of Health and will be introduced from next October. PMID- 27414531 TI - Asthmatics danger. AB - The life-saving nebuliser, used to give high doses of asthma drugs, may become dangerous if patients rely too heavily on it at home. Last week's Drugs and Therapeutics Bulletin, published by the Consumers' Association, warned that nebulisers can produce a false sense of security because the initial rapid improvement wears off in a few hours. People who have repeated attacks of sudden severe asthma may delay seeking further treatment. PMID- 27414534 TI - Brush up on smear tests. AB - Women should be offered cervical smears with a cytobrush as well as the normal spatula, according to Anne Szarewski, specialist in family planning and colposcopy. PMID- 27414535 TI - Aids information needed. AB - A US study has shown that nurses want more information on all the issues surrounding HIV and AIDS infection. PMID- 27414536 TI - Blood pressure and stroke. AB - High blood pressure is not associated with an increased risk of stroke in elderly women, according to research from South Tyneside. PMID- 27414537 TI - Locating lung cancer genes. AB - British and Dutch scientists are on the way to tracking down the gene that causes lung cancer. PMID- 27414538 TI - Depression and renal treatment. AB - Patients with psychiatric disorders who are being treated for end stage renal failure are less likely to have a psychiatric illness one year later, a Nottingham study has shown. PMID- 27414539 TI - Helpful computer programs. AB - Computer programs used for health education have proved popular with nurses, according to a Glasgow study. PMID- 27414540 TI - A bullseye for nursing standard. AB - TheNursing Standardhas gone from strength to strength since its launch in September. Published by Scutari Projects, Britain's new nursing weekly has built up a strong core of regular readers during its first five months and is set to welcome many more in 1988. PMID- 27414541 TI - Nurses honoured in new year's list. AB - Yet again Britain's nurses feature strongly in the Queen's New Year's Honours List. Among those to receive awards are two nurses who cared for victims of the Zeebrugge ferry disaster. PMID- 27414542 TI - Report compares unfair SDP cuts. AB - Government plans to abolish special duty payments could cut nurses' incomes by up to 15 per cent, plunging them still further below comparability with other public and private sector workers, says a new report. PMID- 27414545 TI - Changes could undermine education. AB - Proposed changes in the national curriculum could seriously undermine health education in schools, according to the Royal Society of Health. PMID- 27414544 TI - Baby's death spotlights cuts in neo natal services. AB - Further incidences of cuts in neo-natal intensive care services due to chronic shortages of specially trained nurses have been uncovered both north and[Illegible word] of the country. PMID- 27414546 TI - New social fund could cause hardship. AB - The Government's new social fund will mean sweeping cuts in the help available to the poorest members of the community according to the Labour Party. PMID- 27414547 TI - Sharing approach for computers. AB - A more sharing approach to the use of microcomputers in nursing education and a move towards a more educationally creative 'contents free' software were called for during a recent conference. PMID- 27414548 TI - Cash injection for regional services. AB - Over L40 million has been earmarked for supra regional services in England as part of the Government's December announcement of extra funds for the NHS. PMID- 27414549 TI - NHS Staff 'free to talk to the press'. AB - Nurses are free to talk to the Press so long as they do not disclose information about individual patients. That at least seems to be the view of Health Minister Tony Newton. For the Minister was challenged about the Government's attitude to health workers talking to the media and threats of disciplinary measures. The threats followed the uproar over the 'Baby David' case when it was suggested doctors and hospital staff who commented on the case could be in trouble. PMID- 27414551 TI - New patient hospital guides. AB - Mothers to be and elderly patients are among those to benefit from a new series of information booklets introduced by Sand well Health Authority. PMID- 27414550 TI - Cool response to report on YTS placements. AB - The publication of the Price Waterhouse feasibility report on YTS has drawn a cool response from the nursing unions. PMID- 27414552 TI - No scapegoats for child abuse. AB - The Government has been warned that it risks more tragedies like the death of toddler Tyra Henry by making health and social workers the scapegoat for child abuse cases rather than providing funding for improved services. PMID- 27414553 TI - Management appointments. AB - Two new unit general managers have been appointed in West Berkshire Health Authority as part of the reduction in the number of management units from seven to three. PMID- 27414554 TI - Community care guide from mind. AB - A new approach to community care services at local level has been set out by the mental health group MIND. PMID- 27414556 TI - Hamper winners. AB - A special Christmas gift courtesy of Nursing Standard and Tesco in the form of a superb hamper was delivered to three lucky nurses last month. PMID- 27414555 TI - Rock solid support for protest. AB - Pete Townsend from the rock group The Who threw his full support behind a nursing protest against the proposal to cut special duty payments last month. PMID- 27414557 TI - Vigilance against vandals pays off. AB - South Birmingham Health Authority has commended local residents for their help in combating vandalism in the district's clinics and health centres. PMID- 27414559 TI - Forum critical of funding available for nursing study. AB - Very little provision is made for nurses to be able to study for higher degress and undertake research, according to the RCN's Forum of Integrated and Degree Courses in Nursing. The forum has just published a paper outlining the funding available for those wanting to take nursing courses and condemning the number and size of grants available to nurses. PMID- 27414558 TI - Finance reviews urge caution. AB - Experts in health care financing have urged the Government to be extremely cautious in its examination of alternative sources of funding for the National Health Service. PMID- 27414560 TI - Former college officer dies aged 70. AB - George Hood, renowned for his work on nurse education in the 1960s and 70s died at the age of 70 years last month. PMID- 27414561 TI - Preston nurse wins major award. AB - Preston nurse Valerie Sumner has won SI,650 in the RCN-3M Awards for Accident and Emergency Nursing. Ms Sumner, a Senior Staff Nurse at the Royal Preston Hospital, was officially presented with the award at the recent RCN A&E Nursing Forum annual conference. PMID- 27414562 TI - Aids forum concern over home office suggestions. AB - The RCN's Forum on AIDS has expressed concern at suggestions from the Home Office that legislation may be introduced against people who 'deliberately, knowingly or carelessly transmit HIV'. According to the College's AIDS Nursing Adviser, Richard Wells, if the Government's health education campaign is effective then potential for spreading the virus should be minimal. PMID- 27414563 TI - New year message from the president. AB - Saying goodbye to the old and ready for the challenges of the new, RCN President Maude Storey delivers a special New Year message to the College membership. PMID- 27414565 TI - New year's Honours for leading scottish figures. AB - Two of Scotland's leading figures in nursing are among those to be honoured in the Queen's New Year's Honours list. PMID- 27414564 TI - New chief nursing officer for scotland. AB - Mrs Yvonne Moores, who for the past six years has been Chief Nursing Officer at the Welsh Office has been appointed as the new Chief Nursing Officer for Scotland. PMID- 27414567 TI - New units for woodilee hospital. AB - The Greater Glasgow Health Board is to go ahead with plans to build three new 30 bedded units at Woodilee psychiatric hospital, following approval from the Home and Health Department. PMID- 27414566 TI - NHS Record defended on Glasgow visit. AB - Scottish Health Minister Michael Forsyth defended the Government's record on the NHS during a recent visit to the Royal Hospital for Sick Children at Yorkhill, Glasgow. PMID- 27414568 TI - More individual support to develop nurses' potential. AB - Talented nurses are not getting enough individual support to develop their potential says a report from the Scottish Home and Health Department. PMID- 27414569 TI - New hospital for campbeltown. AB - A new hospital development in Campbeltown has received the approval of Health Minister for the Scottish Office, Mr Michael Forsyth. The L4.4 million hospital to be built by Argyll and Clyde Health Board will replace the three existing hospitals and it is hoped that the development will alleviate deficiencies within the existing accommodation and improve [illegible word] vices for patients and staff in [illegiblel word] Kintyre area. PMID- 27414570 TI - Specialist group planned for scottish handicapped. AB - Members of the Royal College of Nursing's Mental Handicap Society are hoping to establish a specialist Scottish national interest group early this year. PMID- 27414571 TI - Competitive tendering for ayrshire support services. AB - Scottish Health Boards have been told by the Government to take immediate action to introduce more competitive tendering for services such as hospital cleaning and catering. PMID- 27414572 TI - Scottish nurses to air their views. AB - Twenty Scottish nurses will be among 100 women sharing their ideas and opinions on a new Scottish television series. PMID- 27414573 TI - Pensioners aid announced at edinburgh rally. AB - The Shadow Chief Secretary to the Treasury, Gordon Brown has challenged the Prime Minister to introduce new measures to help pensioners pay their fuel bills in winter. PMID- 27414574 TI - Screening for scots women. AB - A new cervical cancer screening service is to be made available to women in Scotland aged between 20 and 60 years it was announced recently by Mr Michael Forsyth MP, Health Minister at the Scottish Office. By the end of 1988, all Health Boards in Scotland will aim to have a fully computerised call and recall system. Women who have not been screened will be contacted and those who have been screened will be recalled every five years for another smear test. PMID- 27414575 TI - Watchdog. AB - I am 16 years of age and a Care Assistant at a residential home, and I would like to become a nurse. When I am 18 I would like to begin nurse training and need some help on what to do to achieve this goal. PMID- 27414576 TI - Directions. AB - Generally, the person with a mental handicap was born with it and will that handicap throughout life. Others may, as a result of an accident, sustain permanent brain damage and are mentally handicapped thereafter. While their handicap is not an illness or disease per se, their functioning ability endures an impairment that may range from mild to profoundly severe and may, in some instances, be compounded by physical handicap. Within the health professions an impaired function, whether mental or physical, mild or severe, warrants attention and appropriate action. In the United Kingdom, it was determined as early as 1847 that people with mental handicap are educable, and progress to that end in nearly a century and a half has been particularly noteworthy in the last 25 years. PMID- 27414577 TI - Down in the mouth. AB - Been to see the dentist lately? Probably not, if recent figures from the National Consumer Council are anything to go by. Launching a new booklet, 'You and Your Dentist - a Guide to Patients' Rights', the NCC notes that less than half the adult population in Britain has a dental check-up regularly. Fear of pain is a great deterrent, and as controversy continues to rage over the proposal to introduce charges for dental check-ups, there are suggestions that payment of a fee will discourage regular attendance. PMID- 27414578 TI - Burn-out. PMID- 27414579 TI - Avoiding accidents. AB - More than 5,000 people the from accidents in the home every year and a staggering 3,000 000 seek medical attention according to recent figures from the Department of Trade and Industry. Age groups most at risk are those over 65 and children under five, and falls account for the highest numbers of deaths and injuries. Other major accidents include cuts, being hit by an object, poisoning and suffocation or choking. PMID- 27414580 TI - The play's the thing. AB - The concept of dramatheropy suggests stage performances and script rehearsals. In fact the professional body representing dramatherapists, the British Association for Dramatherapists, describes it as drama in the therapeutic context. And if used with the right approach dramatherapy can uncover many deeply hidden problems, according to Ted Wharam, one of four Nurse Therapists in East Yorkshire and Hull Health Authority. PMID- 27414581 TI - Continuous ambulatory peritoneal dialysis. AB - When conservative treatment of renal failure is no longer effective and renal function has deteriorated to the point where death will follow, dialysis therapy (cleansing of the blood by removing the waste products which the kidney usually removes) must be started. Continuous Ambulatory Peritoneal Dialysis (CAPD) is a relatively new form of dialysis which allows greater freedom than haemodialysis. PMID- 27414582 TI - A limited issue. AB - A rare agreement has been reached between the British Medical Association and the Royal College of Nursing on limited prescribing powers for community nurses. PMID- 27414583 TI - Career moves. AB - The image of nursing - and of male nurses - in the eyes of the public must be radically altered if the profession is to attract more men. PMID- 27414584 TI - No death so sad. AB - Facing up to the death of a child is bad enough. PMID- 27414585 TI - Cash compensation fight goes on. AB - Britain's 1,200 HIV infected haemophiliacs are still fighting for cash compensation despite the Government's promise of L10 million. PMID- 27414586 TI - Call for additional resources for NHS. AB - A new back-bench Bill has been launched demanding additional resources to meet the ideals of the National Health Service. PMID- 27414588 TI - Decisions on hepatitis b jab in the offing. AB - Decisions on whether to immunise all nurses against the threat of Hepatitis B are expected to be taken within the next few weeks. PMID- 27414587 TI - Crime statistics show cost to NHS. AB - The latest National Health Service crime statistics sparked off a Commons row wit the revelation that theft, fraud and arson are costing the health service over L4,500 every day of the year. PMID- 27414589 TI - AIDS report to predict spread in early 1990s. AB - A report on the spread of AIDS and HIV infection in Britain is expected to be delivered to Ministers shortly. It will predict the estimated scale of the problem in the early 1990s and its contents are expected to provide a basis for medium term planning on combating the disease. PMID- 27414590 TI - Objective questions in orthopaedic nursing objective questions in orthopaedic nursing Cole P Churchill Lovingstone 212pp L8.50 0-443-02473-1. AB - The presentation of Elizabeth Evans's book is good; typography and her style make it very readable; and it is well illustrated throughout. The first of two sections deals with multiple choice (MCQs) and the true/ false type questions. The second contains nursing care studies with relevant MCQs for the reader to answer. PMID- 27414592 TI - The Health and Safety Directory The Health and Safety Directory Hastings M R City Financial/Kluwer 962pp L39 1-870080-22-X. AB - Although I have reviewed many books over the last decade, I had not until now been asked to review a directory. My main decision was the criteria on which I would judge the book. PMID- 27414591 TI - Adam Adam Adair K Hodder & Stoughton 222pp L11.95 0-340-40677-1. AB - Katherine Adair, a mother, kept a diary of what occurred from the time when her son Adam was diagnosed with leukaemia to his death almost two years later. It is a touching insight into family life and emotions whilst living with this form of childhood cancer and subsequently their coping with Adam's death. PMID- 27414593 TI - Your Child's Health Your Child's Health I Blumenthal Published by Faber & Faber 372pp L6.95 0-571-14707-0. AB - For the parent with an enquiring mind Ivan ' Blumenthal provides a wealth of information about a wide range of medical dis- I orders from which a child may suffer. Structured in the form of questions a parent may ask of a doctor or nurse, the book describes in considerable depth the diagnosis and treatment of childhood illness. PMID- 27414594 TI - Medical-Surgical Nursing Luckmann J , Sorensen K C Medical-Surgical Nursing 3rd edition W B Saunders 2126pp t39.50 0-7216-5815-6. AB - While reviewing Joan Luckmann and Karen Sorensen's latest edition, I was reminded of an old tutor who when presented with a hefty study or project by one his students used to throw it on his desk, wait for effect, and then comment 'Hmmm...about the right weight.' This edition, like its predecessor, is not only hefty but 'the right weight' in the sense that the old tutor always meant - its range and scope of content. The sheer volume of content remains impressive indeed. PMID- 27414595 TI - Alternative NHS funding. AB - I read with interest the advertisements carried by the Sunday magazines calling for people to join the nursing profession. They paint an idyllic lifestyle and suggest that personal satisfaction and that wonderful feeling of having cared for someone will be the future way of life for you if you enter the nursing profession. Yet, we read daily that nurses are leaving the profession at an alarming rate because of low pay, bad working conditions and low morale. PMID- 27414596 TI - Sport injury clinics. AB - I am currently on the ENB 219 orthopaedic course at Nottingham. During my course, I have to do a research project as part of my final assessment. I am hoping to find out if there is a need for a sports injury clinic (non private) within the accident and emergency department here. PMID- 27414597 TI - Head above water. AB - Help! Who can help us? The Government knows very well that nurses will not walk off wards. They have the ability to bring about the abolition of special duty payments without any trouble at all. PMID- 27414598 TI - False Assumptions. AB - Mrs K M Regan is clearly out of touch with the views of the nursing profession on the subject of special duty payments (week ending December 19). PMID- 27414599 TI - No scapegoats. AB - As Convenor for West Berkshire, I would like to reply to Adrian Robert's letter in the Nursing Standard (week ending November 28). PMID- 27414600 TI - Losing out. AB - Six months ago I changed from being a Sister on permanent night duty, to a day Sister on an elderly care ward. PMID- 27414601 TI - Time to stop taking from NHS. AB - I have read your article about nurses duty payment being cut. First I must say I am a nursing auxiliary on night duty. I have a family on night duty. I have a family, and I am also a NUPE shop steward for night duty. I must say if this special duty payment is cut my wages will be nothing at the end of the month. I work night for more money because my husband is out of work and we just get by on what I earn. I would like all your help and information please about this matter. Don't you think this Government has taken enough from the National Health Service as it is? We must stop them. Bulwell, Nottingham. PMID- 27414602 TI - Unkind cuts. AB - It is horrifying that the Government has the audacity to consider cutting special rates for nurses. We can hardly survive on the wages we receive now. PMID- 27414603 TI - Stretched to the limit. AB - In reply to comments by student nurse Lorenzo Visentin (Letters, week ending December 5), it is not occupational health departments that are refusing to give Hepatitis B to the student nurses. PMID- 27414604 TI - Trivial pursuit. AB - I commend Nurse Snowden (Letters, Nursing Standard week ending December 19) for putting forward the patients' view. However one must be cautious in interpreting people's views; I have heard suggestions on uniform from some male patients that I doubt Nursing Standard would print (unless on page 3? ). It is essential to see such views in context- for example, if she were to ask 'what do you think is most professional for a nurse, a smart cap or a high standard of nursing?' she might not get 100 per cent in favour of caps. PMID- 27414605 TI - Ring out the old, ring in the new. AB - Bleak outlook lor 1988 at Great Ormond Street Hospital - it's the year when the copyright runs out for M Barrie's evergreen Peter Pan. The royalties, donated by the author to the hard-pressed hospital, will no longer be coming in. PMID- 27414606 TI - Good news for cats, bad news for contraception. AB - The search goes on for the perfect contraceptive. Alas, one promising development has already earned a resounding raspberry from seven out of ten women. Quizzed by Schering Health Care, women said that a male pill might work well - but would the males? Not only would they disbelieve hopeful new acquaintances who pleaded: 'It's all right-I'm on the pill', they wouldn't even believe their own husbands. 'They didn't even trust their husbands to remember to put out the cat at night,' say Schering, 'so how could they expect him to remember to take the pill?'. PMID- 27414607 TI - Diary Strictly off the record. AB - Sick of all those nurse of the year competitions who nearly always choose young and glamorous angels as winners? Turn to the USA, where the process has reached its logical conclusion. Yes, folks, the new Miss America is a nurse. PMID- 27414608 TI - Water cheek! AB - A new cost-saving idea has caused ructions at the Western general Hospital in Edinburgh. Staff who bring their own tea and coffee will now be charged 5p for the hot water they use. Heating the water and washing the tea-cups still costs money, says the hospital. PMID- 27414609 TI - Flannel job. AB - January 3 marked the day when Mrs Thatcher became the longest serving Prime Minister this century. Perhaps this explains the strong sense of time warp which hovers round her recent pronouncement that a loss of 30,000 nurses a year from the National Health Service is 'not an unduly large amount' - because 'they are young and attractive and a lot of them go to get married and have children'. PMID- 27414610 TI - Winter of discontent. AB - If you're feeling bloated, blue and would rather stay in bed all day than set out for work, don't blame the Christmas excesses, blame the winter. PMID- 27414611 TI - Sights and sounds. AB - Top marks to Shetland, who realise they may need a gimmick to recruit nurses to an area which boasts place names like Unst, Foula and Yell. They have produced an audio cassette about the local attractions which includes music by Mark Knopfler of Dire Straits - not a comment on the landscape, or even (alas!) because he lives there, but because [illegible word] the theme music of the enchanting Scottish-set film Local Hero. PMID- 27414612 TI - Finland. AB - Nurses from 52 countries shared the floor with economists, architects, doctors and sociologists when the 25th international hospital congress assembled in Helsinki, Finland recently. PMID- 27414613 TI - Switzerland. AB - Moves are being made internationally to improve the health and safety of nurses. PMID- 27414614 TI - Canada. AB - Senaca College in North York, Ontario has developed a one year part time air ambulance training course for registered nurses. PMID- 27414615 TI - United states. AB - In New York nurses are to receive training to identify and help women who are battered during pregnancy. PMID- 27414616 TI - China. AB - Nurses in Quidong county, China, are assisting in a programme to immunise all new born babies to cut down the high incidence of Hepatitis B and liver cancer in the area. About 9,000 babies are vaccinated each year in a population of 700,000. The protection rate is around 85 per cent and the prevention strategy extends to control aflatoxin contamination on an individual basis. PMID- 27414617 TI - Good health in store. AB - As the January sale signs go up and hoards of bargain hunters flood to the doors of Marks and Spencer in Glasgow's Argyle Street, Sheila Rodger braces herself for the second wave of the busiest shopping period of the year. PMID- 27414619 TI - Listings. AB - Nursing Standard's listings section is a completely free service for its readers. To ensure maximum publicity for any event connected with your profession, be sure to let us I know so that it can be included in our exhaustive [Illegible Word] wide guide to what's on nursing. PMID- 27414618 TI - Restored to life. AB - More than a decade ago the Government produced a White Paper, 'Better Services for the Mentally III', recommending that each district health authority should provide a comprehensive range of local services to meet the mental health needs of the population for which it had responsibility. PMID- 27414620 TI - Transparent patch for hormone treatment. AB - Hormone treatments to relieve menopausal symptoms in women who have had a hysterectomy can now be delivered through the skin, rather than taking a tablet. PMID- 27414622 TI - Food data pack. AB - Heinz has produced an information pack giving details of theingredients and nutritional value of its complete range of food products. The pack will be updated regularly. For a free copy of the Nutrition Data Pack send a large, 62 pence stamped, addressed envelope to: 'Heinz Nutrition Office, 121 Gloucester Place, London W1H 3PJ. PMID- 27414621 TI - Alarm system for detecting gas leaks. AB - Protection for elderly people against poisonous gas leaks is the aim of a new alarm system from Cory Technology. PMID- 27414623 TI - Simple filter for home renal dialysis. AB - Amatek have made life easier for home renal dialysis patients byproducing a simplified filter housing. PMID- 27414624 TI - More mobile chairs for the elderly. AB - A range of chairs designed to give greater mobility to the elderly andinfirm has been launched by Nesbit Evans, hospital furniture suppliers. PMID- 27414625 TI - Hoist design for baths. AB - Work is now underway to develop a student's hoist design into a commercial product for lifting elderly and disabled people into baths. PMID- 27414626 TI - Hyper active. AB - You know what they say about too many cooks! Well, here all the students appear to be having a go - but at what is left to the imagination as the operating table looks far too small for a patient. PMID- 27414627 TI - Danielle Bassett: Opening Up the Brain with Network Science. AB - Here's the drill. Upon waking, count down from 100 to one as quickly as possible. Next, recite the alphabet, giving each letter a corresponding word partner (A, antler; B, bargain; C, cartoon, for example). After that, crank out several lists, numbering each of the items: 20 men's names, 20 women's names, 20 food items, 20 words beginning with the same letter. When you're done, close your eyes, count to 20, and open them. Your mind, according to Mental Aerobics: Exercises for a Stronger, Healthier Mind [1], is now warmed up and ready to face the day. PMID- 27414628 TI - Stem-Cell Work Yielding New Approach to Disease: Induced Pluripotent Stem-Cell Research Soars, Spurring Dreams of Clinical Applications. AB - Interest in stem cells escalated in 2006 when scientists figured out how to reprogram some specialized adult cells to assume a stem-cell-like state. Called induced pluripotent stem cells (iPSCs), these cells opened the door to a range of potential applications, including generating cells and tissues to replace those that are faulty or missing in patients with cancer, diabetes, cardiovascular disease, or other maladies (Figure 1). Visions of new treatments and even cures for debilitating and fatal illnesses proliferated, and some of that work is well under way (see "A Wealth of Research"). Now, ten years later, those visions are looking more like real possibilities as research moves from the lab to the clinic and expands toward a greater understanding of the basic science behind stem cells and its applications. PMID- 27414629 TI - Thumbs Up for Stem Cells: Popular Reprogramming Methods Show No Systematic Mutations. AB - Researcher Jeanne Loring thinks she has a good method for reversing the symptoms of Parkinson's disease (Figure 1), and she believes this method-a stem-cell therapy-will find its way to clinics in as little as twoand-a-half years. Although the work has progressed very smoothly, one thing has continued to nag at her: is it actually safe to transplant induced pluripotent stem cells (iPSCs), or are these cells potentially dangerous to patients? PMID- 27414630 TI - Steering Organoids Toward Discovery: Self-Driving Stem Cells Are Opening a World of Possibilities, Including Drug Testing and Tissue Sourcing. AB - Since the 1980s, stem cells' shape-shifting abilities have wowed scientists. With proper handling, a few growth factors, and some time, stem cells can be cooked up into specific cell types, including neurons, muscle, and skin. PMID- 27414631 TI - Healing the Burn: Advances in Burn Treatment Technology Aim to Save Lives, Lessen Pain and Scarring. AB - When brothers Jamie and Glen Selby, aged 5 and 7, arrived at the Shriners Burns Institute in Denver, Colorado, in July 1983, more than 97% of their skin had been destroyed by a fire they had accidentally started while playing in an abandoned house. The boys were so badly burned that their outlook was grim-a 6-year-old friend who was also in the fire died from his injuries?but Jamie and Glen were lucky. Not only did they survive, but they were also some of the first patients to benefit from a new burn treatment nicknamed test-tube skin. PMID- 27414632 TI - Electrical Stimulation: A Panacea for Disease?: DARPA Investigates New Bioelectrical Interfaces for a Range of Disorders. AB - It seems simple: send a small electrical current to a major nerve in the body and stimulate hormones and organs to react in the way you want. New efforts by research teams are doing just that, zapping peripheral nerves attached to major organs in the hopes of addressing problems as diverse as inflammatory bowel disease, chronic pain, and posttraumatic stress disorder. Thanks to the continued advance of smaller and more efficient electronics, researchers are finding new ways to develop implantable bioelectrical devices to treat a wide range of ailments. PMID- 27414633 TI - The Virtual Physiological Human: The Physiome Project Aims to Develop Reproducible, Multiscale Models for Clinical Practice. AB - The Physiome Project was initiated by the International Union of Physiological Sciences (IUPS; www.iups.org) in 1997 to bring multiscale engineering modeling approaches to the physiological interpretation of the wealth of molecular data that was becoming available at that time [1]. The discipline of physiology, which with anatomy underpins medical practice, had lost its traditional central position in the biological sciences (at least from a funding perspective) to molecular biology, despite the very small impact molecular biology has had on the diagnosis and treatment of disease. While diseases and drugs certainly operate at the molecular level, the regulation of genetic transcription and, hence, the expression of proteins (the building blocks of life) are both highly dependent on environmental factors governed by the physical world in which molecular biology operates. Engineering-in particular, the rapidly growing field of bioengineering is the discipline that has the integrative skills and tools to put the molecular pieces of Humpty Dumpty back together again. PMID- 27414634 TI - Opening New Worlds for Those with Autism: Technology Is Creating Great New Possibilities for Those on Every Part of the Spectrum. AB - In April 2016, in honor of Autism Acceptance Month, Apple released a video that quickly went viral, racking up more than 4 million views in its first few days (https://youtube/oMN2PeFama0). It shows a teenage boy named Dillan whose life has been completely transformed by the use of an iPad. As a nonverbal person, until he learned to use the device, he had no way of showing people that he was aware, thoughtful, paying attention, and eager to communicate. He just didn't have the necessary control over his body?s vocal apparatus to let people know he was really there. Suddenly, this little piece of 21st-century technology gave him that ability. For him, the technology has been literally life-changing. PMID- 27414635 TI - Deconvolution: It Fans Back, Out, and Ahead [Retrospectroscope]. AB - The origins of convolution and its further and rather complex historical development were dealt with in detail by Alejandro Dominguez in a previous article [1]. We saw there that it can be traced back to the middle of the 18th century; however, its modern form and use are not more than 50 or 60 years old. PMID- 27414636 TI - Roux-en-Y gastric bypass for obesity after Belsey-Mark IV for large hiatus hernia and intrathoracic stomach, in combination with gastroesophageal reflux disease. AB - BACKGROUND: Obesity is an increasing problem worldwide; patients who remain obese after non-surgical interventions are potential candidates for surgical intervention. Laparoscopic Roux-en-Y gastric bypass (RYGB) has proven its effects on excess weight loss and its positive effect on comorbidities and also, on reflux correction. CASE REPORT: Our patient, a 53-year-old male, with a BMI of 45 kg/m2 and type 2 diabetes, underwent a Belsey-Mark IV procedure in another center because of a large hiatus hernia and intrathoracic stomach, in combination with gastroesophageal reflux disease (GERD). He consulted at our center concerning his morbid obesity. After a positive preoperative evaluation a RYGB was performed with an uneventful postoperative course. CONCLUSION: RYGB is a safe and feasible procedure to perform after a Belsey-Mark IV procedure. To our knowledge, this is the first and only report of a RYGB after a Belsey-Mark IV procedure. There were no intra-operative complications and 18 months follow-up was unremarkable, with a 78.10% excess weight loss (EWL), at 86 kg, and no remaining symptoms of GERD. We also mention resolution of the patient's diabetes mellitus type 2 measured by the cessation of the glucophage, which is an added health benefit. PMID- 27414637 TI - Isotretinoin: controversies, facts, and recommendations. AB - INTRODUCTION: Since it was introduced to the market by Hoffman-La Roche (Roche) in 1982, isotretinoin has remained the most effective treatment for severe and recalcitrant acne. However, it has also been surrounded by controversy due to its teratogenicity and inconsistent associations with depression, suicidality, inflammatory bowel disease, increases in lipid levels, and elevated transaminases. Areas covered: In this article, we reviewed data regarding safety of isotretinoin and its association with these conditions. A thorough and comprehensive search on the topics was performed using pubmed and google scholar. Expert commentary: Despite common misperceptions, there is weak evidence for increased incidence of depression, suicidality, or inflammatory bowel disease with isotretinoin use. Furthermore, data indicates that transient increases in transaminases and lipid levels do not typically necessitate discontinuation of therapy. We hope to provide clinicians with information necessary to have meaningful discussions with patients regarding the safety and efficacy of isotretinoin. PMID- 27414638 TI - Cognitive enhancement: it's about time. AB - Voelker et al. (2016) discuss the intriguing possibility that faster response times after training result from changes in white matter pathways, and propose that frontal theta activity is important for inducing these changes. We argue that, depending on the specific cognitive processes and brain networks targeted by training, oscillatory activity in other frequency bands could produce similar changes in white matter. Such changes can have a profound effect on brain function and performance if they optimize the timing of information transmission through neural networks. It is not about frequency or speed per se; it is about time. PMID- 27414640 TI - Equine Welfare in England and Wales: Exploration of Stakeholders' Understanding. AB - Investigating how those responsible for the care of nonhuman animals understand the concept of animal welfare is important for animal welfare improvement. In depth interviews with 31 equine stakeholders were used to explore their perceptions and understanding of welfare. The results showed the stakeholders understood the concept of welfare in 4 ways. Firstly, welfare was understood in terms of the provision of resources-for example, food. Secondly, a "horse centered" understanding of welfare was articulated; this understanding included the horses' mental state and was linked to natural behavior. Thirdly, the word welfare had negative connotations, and for some, good welfare was achieved through avoidance of negative states. Finally, interviewees discussed incidents that occurred in their own familiar contexts but suggested that these were not welfare problems. Evidence indicated that the ways in which equine stakeholders understood the concept of welfare might have been acting as a barrier to the alleviation of some equine welfare problems. There is a need for strategies aimed at improving equine welfare to consider stakeholder constructs of welfare and the ways in which these constructs are generated and acted upon. PMID- 27414641 TI - A Cytolethal Distending Toxin Variant from Aggregatibacter actinomycetemcomitans with an Aberrant CdtB That Lacks the Conserved Catalytic Histidine 160. AB - The periodontopathogen Aggregatibacter actinomycetemcomitans synthesizes several virulence factors, including cytolethal distending toxin (CDT). The active CDT holoenzyme is an AB-type tripartite genotoxin that affects eukaryotic cells. Subunits CdtA and CdtC (B-components) allow binding and intracellular translocation of the active CdtB (A-component), which elicits nuclear DNA damage. Different strains of A. actinomycetemcomitans have diverse virulence genotypes, which results in varied pathogenic potential and disease progression. Here, we identified an A. actinomycetemcomitans strain isolated from two patients with advance chronic periodontitis that has a regular cdtABC operon, which, however, codes for a unique, shorter, variant of the CdtB subunit. We describe the characteristics of this CdtBDelta116-188, which lacks the intact nuclear localisation signal and the catalytic histidine 160. We show that the A. actinomycetemcomitans DO15 isolate secretes CdtBDelta116-188, and that this subunit cannot form a holotoxin and is also not genotoxic if expressed ectopically in HeLa cells. Furthermore, the A. actinomycetemcomitans DO15 isolate is not toxic, nor does it induce cellular distention upon infection of co cultivated HeLa cells. Biological significance of this deletion in the cdtB remains to be explained. PMID- 27414642 TI - GNG Motifs Can Replace a GGG Stretch during G-Quadruplex Formation in a Context Dependent Manner. AB - G-quadruplexes are one of the most commonly studied non-B DNA structures. Generally, these structures are formed using a minimum of 4, three guanine tracts, with connecting loops ranging from one to seven. Recent studies have reported deviation from this general convention. One such deviation is the involvement of bulges in the guanine tracts. In this study, guanines along with bulges, also referred to as GNG motifs have been extensively studied using recently reported HOX11 breakpoint fragile region I as a model template. By strategic mutagenesis approach we show that the contribution from continuous G tracts may be dispensible during G-quadruplex formation when such motifs are flanked by GNGs. Importantly, the positioning and number of GNG/GNGNG can also influence the formation of G-quadruplexes. Further, we assessed three genomic regions from HIF1 alpha, VEGF and SHOX gene for G-quadruplex formation using GNG motifs. We show that HIF1 alpha sequence harbouring GNG motifs can fold into intramolecular G-quadruplex. In contrast, GNG motifs in mutant VEGF sequence could not participate in structure formation, suggesting that the usage of GNG is context dependent. Importantly, we show that when two continuous stretches of guanines are flanked by two independent GNG motifs in a naturally occurring sequence (SHOX), it can fold into an intramolecular G-quadruplex. Finally, we show the specific binding of G-quadruplex binding protein, Nucleolin and G quadruplex antibody, BG4 to SHOX G-quadruplex. Overall, our study provides novel insights into the role of GNG motifs in G-quadruplex structure formation which may have both physiological and pathological implications. PMID- 27414643 TI - Differences on Primary Care Labor Perceptions in Medical Students from 11 Latin American Countries. AB - BACKGROUND: The shortage in Latin-American Primary Care (PC) workforce may be due to negative perceptions about it. These perceptions might be probably influenced by particular features of health systems and academic environments, thus varying between countries. METHODS: Observational, analytic and cross-sectional multicountry study that evaluated 9,561 first and fifth-year medical students from 63 medical schools of 11 Latin American countries through a survey. Perceptions on PC work was evaluated through a previously validated scale. Tertiles of the scores were created in order to compare the different countries. Crude and adjusted prevalence ratios were calculated using simple and multiple Poisson regression with robust variance. RESULTS: Approximately 53% of subjects were female; mean age was 20.4+/-2.9 years; 35.5% were fifth-year students. Statistically significant differences were found between the study subjects' country, using Peru as reference. Students from Chile, Colombia, Mexico and Paraguay perceived PC work more positively, while those from Ecuador showed a less favorable position. No differences were found among perceptions of Bolivian, Salvadoran, Honduran and Venezuelan students when compared to their Peruvian peers. CONCLUSIONS: Perceptions of PC among medical students from Latin America vary according to country. Considering such differences can be of major importance for potential local specific interventions. PMID- 27414645 TI - Whole Mitochondrial Genome Sequencing and Re-Examination of a Cytoplasmic Male Sterility-Associated Gene in Boro-Taichung-Type Cytoplasmic Male Sterile Rice. AB - Nuclear genome substitutions between subspecies can lead to cytoplasmic male sterility (CMS) through incompatibility between nuclear and mitochondrial genomes. Boro-Taichung (BT)-type CMS rice was obtained by substituting the nuclear genome of Oryza sativa subsp. indica cultivar Chinsurah Boro II with that of Oryza sativa subsp. japonica cultivar Taichung 65. In BT-type CMS rice, the mitochondrial gene orf79 is associated with male sterility. A complete sequence of the Boro-type mitochondrial genome responsible for BT-type CMS has not been determined to date. Here, we used pyrosequencing to construct the Boro-type mitochondrial genome. The contiguous sequences were assembled into five circular DNA molecules, four of which could be connected into a single circle. The two resulting subgenomic circles were unable to form a reliable master circle, as recombination between them was scarcely detected. We also found an unequal abundance of DNA molecules for the two loci of atp6. These results indicate the presence of multi-partite DNA molecules in the Boro-type mitochondrial genome. Expression patterns were investigated for Boro-type mitochondria-specific orfs, which were not found in the mitochondria from the standard japonica cultivar Nipponbare. Restorer of fertility 1 (RF1)-dependent RNA processing has been observed in orf79-containing RNA but was not detected in other Boro-type mitochondria-specific orfs, supporting the conclusion that orf79 is a unique CMS associated gene in Boro-type mitochondria. PMID- 27414644 TI - Genome-Wide Analysis of the bZIP Gene Family Identifies Two ABI5-Like bZIP Transcription Factors, BrABI5a and BrABI5b, as Positive Modulators of ABA Signalling in Chinese Cabbage. AB - bZIP (basic leucine zipper) transcription factors coordinate plant growth and development and control responses to environmental stimuli. The genome of Chinese cabbage (Brassica rapa) encodes 136 putative bZIP transcription factors. The bZIP transcription factors in Brassica rapa (BrbZIP) are classified into 10 subfamilies. Phylogenetic relationship analysis reveals that subfamily A consists of 23 BrbZIPs. Two BrbZIPs within subfamily A, Bra005287 and Bra017251, display high similarity to ABI5 (ABA Insensitive 5). Expression of subfamily A BrbZIPs, like BrABI5a (Bra005287/BrbZIP14) and BrABI5b (Bra017251/BrbZIP13), are significantly induced by the plant hormone ABA. Subcellular localization assay reveal that both BrABI5a and BrABI5b have a nuclear localization. BrABI5a and BrABI5b could directly stimulate ABA Responsive Element-driven HIS (a HIS3 reporter gene, which confers His prototrophy) or LUC (LUCIFERASE) expression in yeast and Arabidopsis protoplast. Deletion of the bZIP motif abolished BrABI5a and BrABI5b transcriptional activity. The ABA insensitive phenotype of Arabidopsis abi5-1 is completely suppressed in transgenic lines expressing BrABI5a or BrABI5b. Overall, these results suggest that ABI5 orthologs, BrABI5a and BrABI5b, have key roles in ABA signalling in Chinese cabbage. PMID- 27414646 TI - The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide Induced Inflammatory Responses in RAW264.7 Macrophages. AB - Eupafolin is a flavone isolated from Artemisia princeps Pampanini (family Asteraceae). The aim of this study was to examine the anti-inflammatory effects of eupafolin in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS induced mouse skin and lung inflammation models and to identify the mechanism underlying these effects. Eupafolin decreased the LPS-induced release of inflammatory mediators (iNOS, COX-2 and NO) and proinflammatory cytokines (IL-6 and TNF-alpha) from the RAW264.7 macrophages. Eupafolin inhibited the LPS-induced phosphorylation of p38 MAPK, ERK1/2, JNK, AKT and p65 and the nuclear translocation of p65 and c-fos. These effects were mainly mediated by the inhibition of JNK. In the mouse paw and lung models, eupafolin effectively suppressed the LPS-induced edema formation and down-regulated iNOS and COX-2 expression. These results demonstrated that eupafolin exhibits anti-inflammatory properties and suggested that eupafolin can be developed as an anti-inflammatory agent. PMID- 27414647 TI - Characterization of Transgenic Silkworm Yielded Biomaterials with Calcium-Binding Activity. AB - Silk fibers have many inherent properties that are suitable for their use in biomaterials. In this study, the silk fibroin was genetically modified by including a Ca-binding sequence, [(AGSGAG)6ASEYDYDDDSDDDDEWD]2 from shell nacreous matrix protein. It can be produced as fibers by transgenic silkworm. The Ca-binding activity and mineralization of the transgenic silk fibroin were examined in vitro. The results showed that this transgenic silk fibroin had relatively higher Ca-binding activity than unmodified silk fibroin. The increased Ca-binding activity could promote the usage of silk fibroin as a biomaterial in the pharmaceutical industry. This study shows the possibility of using silk fibroin as a mineralization accelerating medical material by generating genetically modified transgenic silkworm. PMID- 27414648 TI - Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana. AB - Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1-actin complex, we constructed a homology model of the AtADF1-actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson-Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin. PMID- 27414649 TI - Retrospection-Simulation-Revision: Approach to the Analysis of the Composition and Characteristics of Medical Waste at a Disaster Relief Site. AB - A large amount of medical waste is produced during disaster relief, posing a potential hazard to the habitat and the environment. A comprehensive understanding of the composition and characteristics of medical waste that requires management is one of the most basic steps in the development of a plan for medical waste management. Unfortunately, limited reliable information is available in the open literature on the characteristics of the medical waste that is generated at disaster relief sites. This paper discusses the analysis of the composition and characteristics of medical waste at a disaster relief site using the retrospection-simulation-revision method. For this study, we obtained 35 medical relief records of the Wenchuan Earthquake, Sichuan, May 2008 from a field cabin hospital. We first present a retrospective analysis of the relief medical records, and then, we simulate the medical waste generated in the affected areas. We ultimately determine the composition and characteristics of medical waste in the affected areas using untreated medical waste to revise the composition of the simulated medical waste. The results from 35 cases showed that the medical waste generated from disaster relief consists of the following: plastic (43.2%), biomass (26.3%), synthetic fiber (15.3%), rubber (6.6%), liquid (6.6%), inorganic salts (0.3%) and metals (1.7%). The bulk density of medical relief waste is 249 kg/m3, and the moisture content is 44.75%. The data should be provided to assist the collection, segregation, storage, transportation, disposal and contamination control of medical waste in affected areas. In this paper, we wish to introduce this research method of restoring the medical waste generated in disaster relief to readers and researchers. In addition, we hope more disaster relief agencies will become aware of the significance of medical case recording and storing. This may be very important for the environmental evaluation of medical waste in disaster areas, as well as for medical waste management and disposal. PMID- 27414650 TI - CdtR Regulates TcdA and TcdB Production in Clostridium difficile. AB - Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease and death. Three well characterised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B) and TcdA (toxin A) in the Pathogenicity Locus (PaLoc) and binary toxin (CDT) in the genomically distinct CDT locus (CdtLoc). Toxin production is controlled by regulators specific to each locus. The orphan response regulator, CdtR, encoded within the CdtLoc, up regulates CDT production. Until now there has been no suggestion that CdtR influences TcdA and TcdB production since it is not carried by all PaLoc containing strains and CdtLoc is not linked genetically to PaLoc. Here we show that, in addition to CDT, CdtR regulates TcdA and TcdB production but that this effect is strain dependent. Of clinical relevance, CdtR increased the production of TcdA, TcdB and CDT in two epidemic ribotype 027 human strains, modulating their virulence in a mouse infection model. Strains traditionally from animal lineages, notably ribotype 078 strains, are increasingly being isolated from humans and their genetic and phenotypic analysis is critical for future studies on this important pathogen. Here we show that CdtR-mediated toxin regulation did not occur in other strain backgrounds, including a ribotype 078 animal strain. The finding that toxin gene regulation is strain dependent highlights the regulatory diversity between C. difficile isolates and the importance of studying virulence regulation in diverse lineages and clinically relevant strains. Our work provides the first evidence that TcdA, TcdB and CDT production is linked by a common regulatory mechanism and that CdtR may act as a global regulator of virulence in epidemic 027 strains. PMID- 27414652 TI - Correction: Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran. AB - [This corrects the article DOI: 10.1371/journal.pone.0148149.]. PMID- 27414651 TI - Intestinal Autophagy Improves Healthspan and Longevity in C. elegans during Dietary Restriction. AB - Dietary restriction (DR) is a dietary regimen that extends lifespan in many organisms. One mechanism contributing to the conserved effect of DR on longevity is the cellular recycling process autophagy, which is induced in response to nutrient scarcity and increases sequestration of cytosolic material into double membrane autophagosomes for degradation in the lysosome. Although autophagy plays a direct role in DR-mediated lifespan extension in the nematode Caenorhabditis elegans, the contribution of autophagy in individual tissues remains unclear. In this study, we show a critical role for autophagy in the intestine, a major metabolic tissue, to ensure lifespan extension of dietary-restricted eat-2 mutants. The intestine of eat-2 mutants has an enlarged lysosomal compartment and flux assays indicate increased turnover of autophagosomes, consistent with an induction of autophagy in this tissue. This increase in intestinal autophagy may underlie the improved intestinal integrity we observe in eat-2 mutants, since whole-body and intestinal-specific inhibition of autophagy in eat-2 mutants greatly impairs the intestinal barrier function. Interestingly, intestinal specific inhibition of autophagy in eat-2 mutants leads to a decrease in motility with age, alluding to a potential cell non-autonomous role for autophagy in the intestine. Collectively, these results highlight important functions for autophagy in the intestine of dietary-restricted C. elegans. PMID- 27414653 TI - Resistance Surveillance in Candida albicans: A Five-Year Antifungal Susceptibility Evaluation in a Brazilian University Hospital. AB - Candida albicans caused 44% of the overall candidemia episodes from 2006 to 2010 in our university tertiary care hospital. As different antifungal agents are used in therapy and also immunocompromised patients receive fluconazole prophylaxis in our institution, this study aimed to perform an antifungal susceptibility surveillance with the C.albicans bloodstream isolates and to characterize the fluconazole resistance in 2 non-blood C.albicans isolates by sequencing ERG11 gene. The study included 147 C. albicans bloodstream samples and 2 fluconazole resistant isolates: one from oral cavity (LIF 12560 fluconazole MIC: 8MUg/mL) and one from esophageal cavity (LIF-E10 fluconazole MIC: 64MUg/mL) of two different patients previously treated with oral fluconazole. The in vitro antifungal susceptibility to amphotericin B (AMB), 5-flucytosine (5FC), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), caspofungin (CASP) was performed by broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute documents (M27-A3 and M27-S4, CLSI). All blood isolates were classified as susceptible according to CLSI guidelines for all evaluated antifungal agents (MIC range: 0,125-1.00 MUg/mL for AMB, <=0.125-1.00 MUg/mL for 5FC, <=0.125-0.5 MUg/mL for FLC, <=0.015-0.125 MUg/mL for ITC, <=0.015-0.06 MUg/mL for VRC and <=0.015-0.125 MUg/mL for CASP). In this study, we also amplified and sequenced the ERG11 gene of LIF 12560 and LIF-E10 C.albicans isolates. Six mutations encoding distinct amino acid substitutions were found (E116D, T128K, E266D, A298V, G448V and G464S) and these mutations were previously described as associated with fluconazole resistance. Despite the large consumption of antifungals in our institution, resistant blood isolates were not found over the trial period. Further studies should be conducted, but it may be that the very prolonged direct contact with the oral antifungal agent administered to the patient from which was isolated LIF E-10, may have contributed to the development of resistance. PMID- 27414654 TI - Elephant Management in North American Zoos: Environmental Enrichment, Feeding, Exercise, and Training. AB - The management of African (Loxodonta africana) and Asian (Elephas maximus) elephants in zoos involves a range of practices including feeding, exercise, training, and environmental enrichment. These practices are necessary to meet the elephants' nutritional, healthcare, and husbandry needs. However, these practices are not standardized, resulting in likely variation among zoos as well as differences in the way they are applied to individual elephants within a zoo. To characterize elephant management in North America, we collected survey data from zoos accredited by the Association of Zoos and Aquariums, developed 26 variables, generated population level descriptive statistics, and analyzed them to identify differences attributable to sex and species. Sixty-seven zoos submitted surveys describing the management of 224 elephants and the training experiences of 227 elephants. Asian elephants spent more time managed (defined as interacting directly with staff) than Africans (mean time managed: Asians = 56.9%; Africans = 48.6%; p<0.001), and managed time increased by 20.2% for every year of age for both species. Enrichment, feeding, and exercise programs were evaluated using diversity indices, with mean scores across zoos in the midrange for these measures. There were an average of 7.2 feedings every 24-hour period, with only 1.2 occurring during the nighttime. Feeding schedules were predictable at 47.5% of zoos. We also calculated the relative use of rewarding and aversive techniques employed during training interactions. The population median was seven on a scale from one (representing only aversive stimuli) to nine (representing only rewarding stimuli). The results of our study provide essential information for understanding management variation that could be relevant to welfare. Furthermore, the variables we created have been used in subsequent elephant welfare analyses. PMID- 27414655 TI - Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials. AB - A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV) has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting >=1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged >=9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target population for vaccination (>=9 years old) for which CYD-TDV has a satisfactory safety profile. Long-term safety will continue to be monitored in the ongoing follow-up of efficacy trials. Safety and effectiveness in real-life settings will be assessed through post-licensure studies. PMID- 27414658 TI - Bring Your Skis to the Super Bowl. PMID- 27414656 TI - Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFkappaB pathway. AB - Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2 induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-kappaB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells. PMID- 27414660 TI - Scanning sports. PMID- 27414659 TI - Don't Cook Away Those Nutrients. PMID- 27414657 TI - Resilience Factors in Women with Severe Early-Life Maltreatment. AB - INTRODUCTION: Early-life maltreatment (ELM) has long-lasting negative consequences and is the most important general risk factor for mental disorders. Nevertheless, a number of maltreated children grow up to become healthy adults and have therefore been called 'resilient'. The aim of the current study is to investigate 'resilience factors' in the context of severe ELM. METHOD: The study was part of the large multicenter project Understanding and Breaking the Intergenerational Cycle of Abuse (UBICA). A total of 89 women were examined, 33 with ELM and at least one lifetime mental disorder (nonresilient), 19 with ELM but without lifetime mental disorders (resilient), and 37 without ELM and without lifetime mental disorders (controls). ELM and other circumstances before the age of 18 years were assessed with the Childhood Experience of Care and Abuse (CECA) Interview. Additional relevant person and situation factors were measured with the Structured Clinical Interview for Mental Disorders (SCID-I), International Personality Disorder Examination (IPDE), Difficulties in Emotion Regulation Scale (DERS), Vulnerable Attachment Style Questionnaire (VASQ), Barratt Impulsiveness Scale (BIS), NEO Five-Factor Inventory (NEO-FFI), and Multiple-Choice Vocabulary Intelligence Test (MWT-B). Factor analyses and paired t tests were performed to identify those variables which differentiate best between the three groups. In addition, a discriminant analysis was conducted to detect the accuracy of assigning women to their specific group. RESULTS: The factor analyses revealed 10 resilience factors based on which we could correctly assign 80% of the women to their group in the discriminant analysis. t tests of factor scores showed that resilient and nonresilient maltreated women mainly differed in current individual attributes (e.g. impulsivity, attachment style), while resilient and nonresilient maltreated women differed from controls in both their current individual attributes and their view of their situation as a child. CONCLUSION: The 4 variables neuroticism, extraversion, vulnerable attachment, and perceived loneliness during childhood were identified as most important in differentiating all three examined groups. Therefore, prevention and intervention programs focusing on the individual's development of secure attachment and social competence may be of particular importance in the context of ELM. PMID- 27414661 TI - Wrap-ups. PMID- 27414663 TI - QuikQuiz. PMID- 27414662 TI - The Epidemic That Might Have Been. PMID- 27414664 TI - Coming in sportsmedicine. PMID- 27414667 TI - Competing With the Cold. PMID- 27414668 TI - Frostbitten Feet. AB - In brief The body's response to severe brief cold-protecting the core temperature by reducing circulation to the extremities-makes the feet vulnerable to frostbite. A frostbitten foot should be rewarmed only when there is no danger of refreezing. During rewarming, patients may need heavy sedation as well as treatment for metabolic acidosis, hypoxia, and hypotension. Patients should be kept in bed until edema subsides and blisters are dry. Escharotomy should be delayed until the eschar starts to separate, since it is usually possible to save more tissue than expected. PMID- 27414669 TI - Exercise in the Cold: Is There a Limit? PMID- 27414670 TI - Cardiovascular Syncope. AB - In brief Something as benign as a vasovagal reflex or as serious as hypertrophic cardiomyopathy can cause cardiovascular syncope. A thorough medical history and physical examination often provide clues to the underlying etiology. Laboratory tests such as a head-up tilt test, an event recorder, or a signal-averaged ECG can provide further diagnostic information. Treatment may include such simple measures as recommending that the patient avoid the sight of blood, or it may mean prescribing drug therapy or correcting a heart defect. Usually, an athlete can resume exercise after a syncopal episode, but sometimes modifications of activities are necessary. PMID- 27414671 TI - Diarrhea and Fecal Incontinence. AB - In brief Two endurance athletes developed diarrhea and fecal incontinence each time they exercised strenuously. Such gastrointestinal difficulties are usually benign, but physicians determined that the disorders were an unusual presentation of lumbar spondylolisthesis in a runner and of jejunal diverticulosis in a cyclist. The runner's diarrhea and incontinence resolved when she avoided activities that precipitated her symptoms, and the cyclist's condition resolved with oral tetracycline. PMID- 27414672 TI - Chronic Exercise-Induced Leg Pain in Active People. AB - In brief "Shin splints" is a catchall term for any kind persistent exercise related lower leg pain with no obvious cause. Such pain can originate from a number of conditions, such as medial tibial stress syndrome, stress fracture, compartment syndrome, vascular pathology, nerve entrapment, and others. A methodical work-up designed to detect problems in all anatomic structures from bone to skin will narrow the possibilities and lay the basis for appropriate treatment. PMID- 27414673 TI - Managing Friction Blisters of the Feet. AB - In brief Active people often develop friction blisters on their feet. Although such blisters rarely create significant medical problems, they can be quite painful and can hinder athletic performance. People can decrease the chance of blister formation by wearing properly fitting shoes, doubling up on socks, and applying dressings or lubricants. If lesions do develop, conservative treatment will speed healing and lessen pain and disability. PMID- 27414674 TI - Sciatica: Treating a Painful Symptom. AB - In brief Contrary to popular belief, sciatica, a symptom of lumbar disk herniation, is relatively uncommon. Characteristics include pain in the posterior thigh, lower leg, or foot that is greater than accompanying low-back pain. Sciatic tension tests confirm the presence of sciatica by reproducing the pain. Many patients who have sciatica recover spontaneously; most others can be treated conservatively with limitation of activity, anti-inflammatory medication, and gradual return to full activity. A variety of surgical options are available for patients who have extruded disks and progressive neurologic deficit or severe, persistent, intolerable pain. PMID- 27414675 TI - Spectator Medical Care. AB - Recent world events-including the fear of terrorism during last year's Super Bowl illustrate how vulnerable spectators can be to medical emergencies during sporting events. A physician who studies and coordinates crowd care for events ranging from the Super Bowl to local fairs gives tips on planning and executing a spectator medical plan. PMID- 27414676 TI - Sports Medicine Groups 1992. AB - The following list of professional organizations and resource groups represents the growing diversity in the field of sports medicine. The list also includes government agencies, sports-related groups, and academic centers that are active in tracking sports injuries All entries have been updated from the list THE PHYSICIAN AND SPORTSMEDICINE published in January 1991. The list is divided into three segments: 43 sports medicine organizations, 27 groups and committees that generate sports medicine information, and 15 statistics-gathering groups. Some groups appear more than once; they have been cross-referenced in each instance. Entries in each of the three segments have been arranged alphabetically. When appropriate, we have given the name of an administrative head along with the chief elected officer. While THE PHYSICIAN AND SPORTSMEDICINE does not endorse any of the groups listed, we do encourage readers to contact the ones that interest them. We have included only the essential information about each group; more detailed descriptions can be obtained by calling or writing to the particular group you are interested in. Readers who would like their organization to be added to next year's list should contact THE PHYSICIAN AND SPORTSMEDICINE Organizations Project, 4530 W 77th St, Minneapolis, MN 55435. PMID- 27414677 TI - Exercises You Can Take to Work. PMID- 27414678 TI - Automatic Determination of the Greulich-Pyle Bone Age as an Alternative Approach for Chinese Children with Discordant Bone Age. AB - BACKGROUND: Automated bone age (BA) rating using BoneXpert is being adopted worldwide. This study investigated whether manual matching of hand radiographs could be replaced by BoneXpert for BA ratings of Chinese children with delayed or advanced BA. METHODS: 482 left-hand radiographs from 482 children (aged 2-16 years) with discordant BA were evaluated by BoneXpert and manually by 4 radiology residents using the Greulich and Pyle atlas. Radiographs whose BoneXpert BA deviated by >1 year from manual assessment were rerated by 2 attending radiologists in a blinded manner. RESULTS: Among all 482 radiographs, 46 (9.5%) radiographs were rerated and no radiographs were rejected. Differences between BoneXpert and manual rating of 28 (5.8%) cases were >1 year. The manual BAs of the 28 radiographs were all >10 years and greater than the BoneXpert BAs. The root mean square deviation between the residents and BoneXpert was 0.56 for these children (95% CI 0.53-0.61). CONCLUSION: BoneXpert agreed with manual BA rating in 94.2% of the images. Therefore, BoneXpert could be used as an alternative for the radiology residents to make an initial BA estimation. Modification of BoneXpert should provide greater accuracy for the estimation of BA in children aged >10 years with discordant BA. PMID- 27414679 TI - Trends in Syphilis Partner Notification Among Gay, Bisexual, and Other Men who Have Sex With Men in British Columbia, 2010 to 2013. AB - Chart reviews of 350 randomly sampled syphilis cases of men who had sex with men in British Columbia from 2010 to 2013 revealed no change in the median number of partners per case, and an increasing proportion of partners notified by cases but fewer partners were known to be tested for syphilis. PMID- 27414681 TI - Low Oral Human Papillomavirus Prevalence in Perinatally Human Immunodeficiency Virus-Infected Adolescents. PMID- 27414680 TI - Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study. AB - In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV. PMID- 27414682 TI - Prevalence of Neovaginal High-Risk Human Papillomavirus Among Transgender Women in The Netherlands. AB - BACKGROUND: Worldwide, transgender women are a high burden population for sexually transmitted diseases. Neovaginal high-risk human papillomavirus (hrHPV) infection has been documented among transgender women, but its prevalence remains unclear. The objective of this study was to determine the prevalence of neovaginal hrHPV in a sample of transgender women in The Netherlands. METHODS: Between June 2015 and December 2015, neovaginal samples were obtained from all transgender women who underwent vaginoplasty and attended our outpatient clinic for postoperative follow-up at least 1 year after surgery. High-risk HPV DNA detection and partial genotyping was performed by the HPV-risk assay. Genotyping of non-16/18-hrHPV-positive samples was subsequently performed by GP5+/6+-PCR followed by Luminex suspension array technology. Physical examination and standardized (sexual) history taking was conducted. RESULTS: Valid neovaginal swabs were obtained from 54 transgender women (median age, 40.7 years [range, 19.2-60.3]; median postoperative time, 2.4 years [range, 1.0-34.2]). No transgender women were employed in the commercial sex industry. Of 28 sexually active transgender women, 6 (20%) tested positive for neovaginal hrHPV including types 16, 45, 51, 59, 66, and X. There were no concomitant neovaginal lesions nor neovaginal symptoms. All sexually inactive transgender women tested negative for neovaginal hrHPV. CONCLUSIONS: A prevalence of neovaginal hrHPV infection of 20% is observed in Dutch transgender women, who self-reported to be sexually active. The clinical consequences neovaginal hrHPV infection in transgender women require further attention. PMID- 27414683 TI - Does Living Outside of a Major City Impact on the Timeliness of Chlamydia Treatment? A Multicenter Cross-Sectional Analysis. AB - BACKGROUND: Timely treatment of Chlamydia trachomatis infection reduces complications and onward transmission. We assessed client, process, and clinic factors associated with treatment delays at sexual health clinics in New South Wales, Australia. METHODS: A retrospective review of 450 consecutive clients with positive chlamydia results (not treated at the time of the consultation) was undertaken at 6 clinics (1 urban, 3 regional, and 2 remote) from October 2013. Mean and median times to treatment were calculated, overall and stratified by process steps and clinic location. RESULTS: Nearly all clients (446, 99%) were treated, with 398 (88%) treated in <=14 days and 277 (62%) in <=7 days. The mean time-to-treatment was 22 days at remote clinics, 13 days at regional and 8 days at the urban clinic (P < 0.001). Mean time between the laboratory receipt of specimen and reporting of result was 4.9 in the remote clinics, 4.1 in the regional, and 2.7 days in the urban clinic (P < 0.001); and the mean time between the clinician receiving the result until client treatment was15, 5, and 3 days (P < 0.01), respectively. CONCLUSIONS: At participating clinics, treatment uptake was high, however treatment delays were greater with increasing remoteness. Strategies to reduce the time-to-treatment should be explored such as point-of care testing, faster specimen processing, dedicated clinical time to follow up recalls, SMS results to clients, and taking treatment out to clients. PMID- 27414685 TI - Ocular Syphilis in Context. PMID- 27414684 TI - Antimicrobial Resistance and Neisseria gonorrhoeae Multiantigen Sequence Typing Profile of Neisseria gonorrhoeae in New Delhi, India. AB - Molecular epidemiology of 100 consecutive gonococcal isolates collected between April 2010 and October 2013 from New Delhi was investigated using Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) along with its association with antimicrobial resistance profiles. Neisseria gonorrhoeae isolates were assigned into 60 different sequence types and 43 (71.6%) were novel. Sole representation was seen in 76.6% sequence types. There was significant association between ST6058 and resistance to penicillin (P = 0.00) and tetracycline (P = 0.002). PMID- 27414686 TI - Metabolic Responses and Pacing Strategies during Successive Sprint Skiing Time Trials. AB - PURPOSE: This study aimed to examine the metabolic responses and pacing strategies during the performance of successive sprint time trials (STTs) in cross-country skiing. METHODS: Ten well-trained male cross-country skiers performed four self-paced 1300-m STTs on a treadmill, each separated by 45 min of recovery. The simulated sprint time trial (STT) course was divided into three flat (1 degrees ) sections (S1, S3, and S5) involving the double poling subtechnique interspersed with two uphill (7 degrees ) sections (S2 and S4) involving the diagonal stride subtechnique. Treadmill velocity and VO2 were monitored continuously, and gross efficiency was used to estimate the anaerobic energy supply. RESULTS: The individual trial-to-trial variability in STTs performance time was 1.3%, where variations in O2 deficit and VO2 explained 69% (P < 0.05) and 11% (P > 0.05) of the variation in performance. The first and the last STTs were equally fast (228 +/- 10 s) and ~1.3% faster than the second and the third STTs (P < 0.05). These two fastest STTs were associated with a 14% greater O2 deficit (P < 0.05), whereas the average VO2 was similar during all four STTs (86% +/- 3% of VO2max). Positive pacing was used throughout all STTs, with significantly less time spent on the first than second course half. In addition, metabolic rates were substantially higher (~30%) for uphill than for flat skiing, indicating that pacing was regulated to the terrain. CONCLUSIONS: The fastest STTs were characterized primarily by a greater anaerobic energy production, which also explained 69% of the individual variation in performance. Moreover, the skiers used positive pacing and a variable exercise intensity according to the course profile, yielding an irregular distribution of anaerobic energy production. PMID- 27414687 TI - Seven Passive 1-h Hypoxia Exposures Do Not Prevent AMS in Susceptible Individuals. AB - PURPOSE: The present study evaluated the effects of a preacclimatization program comprising seven passive 1-h exposures to 4500-m normobaric hypoxia on the prevalence and severity of acute mountain sickness (AMS) during a subsequent exposure to real high altitude in persons susceptible to AMS. METHODS: The project was designed as a randomized controlled trial including 32 healthy female and male participants with known susceptibility to AMS symptoms. After baseline measurements, participants were randomly assigned to the hypoxia or the control group to receive the preacclimatization program (seven passive 1-h exposures within 7 d to normobaric hypoxia or sham hypoxia). After completing preacclimatization, participants were transported (bus, cog railway) to real high altitude (3650 m, Monchsjoch Hut, Switzerland) and stayed there for 45 h (two nights). Symptoms of AMS and physiological responses were determined repeatedly. RESULTS: AMS incidence and severity did not significantly differ between groups during the high-altitude exposure. In total, 59% of the hypoxia and 67% of the control group suffered from AMS at one or more time points during the high altitude exposure. Hypoxic and hypercapnic ventilatory responses were not affected by the preacclimatization program. Resting ventilation at high altitude tended to be higher (P = 0.06) in the hypoxia group compared with the control group. No significant between-group differences were detected for heart rate variability, arterial oxygen saturation, and hematological and ventilatory parameters during the high-altitude exposure. CONCLUSION: Preacclimatization using seven passive 1-h exposures to normobaric hypoxia corresponding to 4500 m did not prevent AMS development during a subsequent high-altitude exposure in AMS susceptible persons. PMID- 27414688 TI - Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines. AB - PURPOSE: The benefits of aerobic exercise training on insulin sensitivity in subjects with metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g., fractalkine, omentin, and osteopontin) that are strongly involved in glucose homeostasis and therefore potentially contribute in the exercise-induced changes in insulin sensitivity. Therefore, we aim to examine changes in skeletal muscle RNA expression and plasma levels of novel cytokines after exercise training and correlate these changes to the exercise-induced changes in insulin sensitivity. METHODS: Women with metabolic syndrome (MetS, n = 11) and healthy women (n = 10) participated in a 6-month aerobic exercise training intervention (three times a week, 45 min per session at 65%-85% of individual heart rate reserve). Before and after training, we examined insulin sensitivity (M value during hyperinsulinemic euglycemic clamp) and circulating blood levels of cytokines (venous blood sample; leptin, adiponectin, omentin, fraktalkin, and osteopontin). The skeletal muscle RNA expression of these cytokines (muscle biopsy) was examined in two subgroups (MetS, n = 6; healthy women, n = 6). RESULTS: At baseline, plasma levels of omentin (85.8 +/- 26.2 ng.mL) and adiponectin (5.0 +/- 1.7 MUg.mL) levels were significantly higher in controls compared with MetS (51.1 +/- 27.1; 3.6 +/- 1.1 respectively), and leptin levels were lower in controls (18.7 +/- 11.5 vs 53.0 +/ 23.5 ng.mL). M value was significantly higher in controls (8.1 +/- 1.9 mg.kg.min) than in MetS (4.0 +/- 1.7). Exercise training significantly improved M values in both groups (P < 0.01). Exercise training did not alter plasma and skeletal muscle RNA expression levels of cytokines, but no correlation was observed between changes in cytokine level/RNA expression and M values (P > 0.05). CONCLUSION: Although exercise training successfully improves insulin sensitivity in MetS and healthy women, we found no change in plasma and mRNA expression levels of novel cytokines. PMID- 27414689 TI - High-Intensity Aerobic Exercise Enhances Motor Memory Retrieval. AB - INTRODUCTION: In previous work, acute high-intensity aerobic exercise benefited continuous motor sequence task learning. As memory processes underlying motor sequence learning vary between tasks involving continuous and discrete movements, the objective of the current study was to determine whether the beneficial effects of acute aerobic exercise generalize to the learning of a discrete motor sequence task. METHODS: Sixteen young healthy individuals practiced a discrete motor sequence task preceded by either a period of rest or a bout of high intensity cycling. Participants moved a cursor with a computer mouse to a series of discretely presented targets on a screen. Target presentation followed either a repeated or a random sequence, which allowed the evaluation of implicit sequence-specific motor learning. The change in movement response time over practice (?-ACQ) and from practice to a 24-h "no-exercise" retention test (?-RET) and the rate of improvement over practice (alpha-ACQ) and during the retention test (alpha-RET) were calculated. RESULTS: alpha-RET was greater for the repeated sequence than random sequences after aerobic exercise (P = 0.01), but not rest (P = 0.33). Further, alpha-RET for the repeated sequence was greater after aerobic exercise than for either sequence (repeated, random) in the rest condition (P <= 0.01). There were no differences between sequences and/or conditions for ?-ACQ, ? RET, or alpha-RET (P >= 0.57). CONCLUSION: Our findings show a positive effect of acute high-intensity aerobic exercise on implicit discrete motor sequence learning. Performing exercise before practice increased the rate of improvement at a 24-h delayed retention test, suggesting an effect on the rate of motor memory retrieval. Pairing acute aerobic exercise with motor practice may facilitate learning of discrete movement sequences in sport or rehabilitation settings. PMID- 27414690 TI - Sprint Acceleration Mechanics in Masters Athletes. AB - PURPOSE: The best sprint performances are usually reached between the ages of 20 and 30 yr; however, even in well-trained individuals, performance continues to decrease with age. Although this inevitable decrease in performance has been related to reductions in muscular force, velocity, and power capabilities, these measures have not been assessed in the specific context of sprinting. The aim of this study was to investigate the mechanical outputs of sprinting acceleration among masters sprinters to better understand the mechanical underpinnings of the age-related decrease in sprint performance. METHODS: The study took place during an international masters competition, with testing performed at the end of the warm-up for official sprint races. Horizontal ground reaction force, velocity, mechanical power outputs, and mechanical effectiveness of force application were estimated from running velocity-time data during a 30-m sprint acceleration in 27 male sprinters (39-96 yr). Data were presented in the form of age-related changes and compared with elite young sprinters data. RESULTS: Maximal force, velocity, and power outputs decreased linearly with age (all r > 0.84, P < 0.001), at a rate of ~1% per year. Maximal power of the oldest subject tested was approximately one-ninth of that of younger world-class sprinters (3.57 vs 32.1 W.kg). Although the maximal effectiveness of horizontal force application also decreased with age, its decrease with increasing velocity within the sprint acceleration was not age dependent. CONCLUSIONS: In addition to lower neuromuscular force, velocity, and power outputs, masters sprinters had a comparatively lower effectiveness of force application, especially at the beginning of the sprint. PMID- 27414693 TI - Metacognitive inferences from other people's memory performance. AB - Three studies show that people draw metacognitive inferences about events from how well others remember the event. Given that memory fades over time, detailed accounts of distant events suggest that the event must have been particularly memorable, for example, because it was extreme. Accordingly, participants inferred that a physical assault (Study 1) or a poor restaurant experience (Studies 2-3) were more extreme when they were well remembered one year rather than one week later. These inferences influence behavioral intentions. For example, participants recommended a more severe punishment for a well-remembered distant rather than recent assault (Study 1). These metacognitive inferences are eliminated when people attribute the reporter's good memory to an irrelevant cause (e.g., photographic memory), thus undermining the informational value of memory performance (Study 3). These studies illuminate how people use lay theories of memory to learn from others' memory performance about characteristics of the world. (PsycINFO Database Record PMID- 27414692 TI - Evaluating the safety of phytosterols removed perilla seed oil-based lipid emulsion. AB - OBJECTIVES: The aim of this study was to ascertain the potential toxicity of perilla seed oil-based lipid emulsion (POLE) caused by phytosterols and confirm the efficacy of the technique for removing phytosterols from perilla seed oil, and evaluate the safety of a low phytosterol POLE in a long-term tolerance study in dogs. METHODS: A comparison between a soybean oil lipid emulsion (Intralipid group A) and POLE with high (group B) versus low (group C) levels of phytosterols was made with regard to their effects on the general condition, hematological and biochemical parameters, urinalysis and histopathological changes in nine dogs receiving daily infusions for four weeks at dosage levels of 6, 6, 9 g fat /kg. RESULTS: Dogs in group A and group C remained in good condition and gained weight during the infusion period and no diarrhea or gastrointestinal bleeding occurred. Only a moderate degree of anemia was observed, the biochemical parameters changed only slightly and returned to normal after treatment had ceased. However, the dogs in group B exhibited significant symptoms of 'fat overload syndrome'. Vomiting, diarrhoea and blood in the faeces were observed. Moreover, triglyceridemia, cholesteremia, and dark urine as well as microscopic signs of liver and gastrointestinal tract damage and generalized jaundice were clearly seen. CONCLUSIONS: Phytosterols promote 'fat overload syndrome' in long-term tolerance studies of POLE in dogs by producing cholestatic liver injury and interfering with fat metabolism. And the toxicity of POLE was reduced by removing phytosterols. PMID- 27414694 TI - Combined treatment with 595-nm pulsed dye laser and 1550-nm erbium-glass fractional laser for traumatic scars. AB - Facial scars can be caused by a traumatic event or indeed surgical procedures. Several treatment modalities have been suggested including surgical or resurfacing techniques, autologous fat transfer, and injection of fillers. However, these approaches have varying degrees of success and associated side effects. We report two Korean patients with traumatic scars. Both patients received combined consecutive treatment with 595-nm pulsed dye laser (PDL) and 1550-nm erbium-glass fractional laser. Both patients showed remarkable clinical improvements after a course of sessions. Therefore, simultaneous combined treatment with PDL and fractional laser may be considered a reasonable therapeutic option for traumatic facial scars. PMID- 27414695 TI - Ginkgo biloba and Memory: An Overview. AB - Ginkgo biloba extract has been increasingly popular for the treatment of memory problems. However, it is not commonly understood that this extract is composed of numerous chemicals, including flavonoid glycosides, terpene lactones, biflavones, and other miscellaneous components. It remains to be established exactly which components are biologically helpful. The extracts come from the leaves of the Ginkgo biloba tree which is cultivated extensively for this purpose. Our aging population will consist of approximately 79 million people 65 y.o. or older in the year 2050. Since memory disorders increase dramatically with age, this poses a major challenge to both the pharmaceutical and nutritional industries to provide products which improve or prevent problems with memory. Our culture is based on the ability to recall information, therefore problems with memory are fundamental to our entire social system. Dementias are disorders that affect memory and intellectual functioning, and are caused primarily by Alzheimer's disease and vascular disorders (multi-infarct dementia). New drug therapies have been developed to improve cognition, through stimulation of the cholinergic system. In recent decades, an extract of the leaves of the tree Ginkgo biloba L. has been used to improve memory in these disorders. The European experience with Ginkgo extract is much greater than that of the U.S. Clinical studies to date have indicated a probable therapeutic benefit of Ginkgo biloba extract. Further human studies are needed to identify which clinical population is most responsive to Ginkgo treatment. In addition, it would be very useful to identify which chemical compound or compounds provide therapeutic effects in memory disorders. These bioactive components may be further concentrated for increased benefit in increasing cognitive memory capabilities. In addition, pharmaceutical companies might be able to modify memory-enhancing Ginkgo-derived molecules to increase potency and effectiveness, leading to the next generation of memory-enhancing drugs. PMID- 27414696 TI - Caffeine's Effects on Performance and Mood are Independent of Age and Gender. AB - The purpose of this study was to determine if there were age or gender specific effects of caffeine, as measured by cognitive tasks and mood assessments known to be sensitive to caffeine. The subjects were healthy, non-smoking volunteers between the ages of 18 and 30 (6 male and 6 female), and over the age of 60 (6 male and 6 female). Only low and moderate consumers of caffeine (daily intake < 400 mg) were enrolled in the double-blind, placebo controlled, crossover design. The order of caffeine dosing (placebo, 64, 128, and 256 mg) was counterbalanced by use of a complex Latin Square sequence of administration. Analysis of the data from all measures indicated that the effects of caffeine were no different in either males or females, or in the young or elderly volunteers. A significant dose-dependent improvement in performance of all subjects was observed in a modified version of the Wilkinson Auditory Vigilance Test. Additionally, significant dose-dependent improvements in mood state were observed in all subjects as assessed by the Profile of Mood States, Multiple Affect Adjective Check List, and The Caffeine Analog Scales. The results of this study suggest that the performance and mood enhancing effects of caffeine are neither age nor gender specific. PMID- 27414697 TI - Effects of Dietary n-3 Fatty Acid Deficiency on Morris Water-Maze Performance and Amphetamine-Induced Conditioned Place Preference in Rats. AB - In these studies we examined whether dietary n-3 fatty acid (FA) deficiency in adult male rats was associated with effects on performance in the Morris water maze and with the development of a conditioned place preference to low (0.5 mg/kg) and high (2.0 mg/kg) doses of amphetamine. The male rats used in these studies had been raised for two generations on n-3 deficient diets, which produced an n-6: n-3 FA ratio in brain lipids three times that of animals fed an n-3 adequate diet. Although the two groups did not differ on learning the position of the hidden platform in the Morris water-maze, the n-3 deficient rats did show deficits on a subsequent working memory version of this task, and swam longer distances to reach a visible platform. There were no differences between the groups on the development of a conditioned place preference although, during the initial conditioning cycle, the increase in activity in response to the high dose of amphetamine was apparent only in the n-3 deficient group. These findings provide preliminary support for effects of n-3 FA deficiency on working memory, but not on motivational processes as measured by response to a drug reward. PMID- 27414698 TI - Effects of Different Levels of Protein and Environmental Stimulation on the Behavior of Young Rats Tested in the Elevated Plus-Maze. AB - The interaction between the effects of different levels of protein malnutrition and environmental stimulation was investigated in young male rats in the elevated plus-maze (EPM). Litters (dam plus 6 male and 2 female pups) were fed a 16% ( CONTROL: C), 10% (Malnourished: M10) or 6% (Malnourished: M6) protein diet. Half of the litters were daily exposed to additional stimulation (CS, MS10 or MS6), while the other half was maintained in normal rearing conditions (CN, MN10 or MN6). The stimulation (handling) consisted of holding the rat in one hand and gently touching the dorsal part of the body with the fingers for 3 min. On the 22nd day of life (weaning), two male pups from each group were tested in the plus maze. Two male pups continued to receive the same diet as their mothers, and the other two were fed a non-purified lab chow diet until 35 days of age when they were tested in the plus-maze (LN, LS, LN10, LS10, LN6 and LS6 groups). Results showed that environmental stimulation increased open arms exploration both at 22 and 35 days of age, indicating an anxiolytic effect of this procedure. Younger rats (22 days of age) explored significantly more the open arms of the maze as compared with older rats (35 days of age), indicating an increase in anxiety with age. M6 animals showed significantly higher percentages of open arm entries and less frequent attempts to enter open arms in the maze as compared with C and M10 animals. These results suggest that even a short period of protein deficiency can produce alterations in the emotional response of rats in the elevated plus-maze. In addition, the data demonstrated that protein deficiency more severe than 10% is necessary to produce behavior alterations in the EPM test. PMID- 27414699 TI - Effects of High Dietary Protein on Coping Behavior, Memory Performance, and Sensory Discrimination in Rats. AB - Rats consuming a high-protein diet (HP; 50% casein) have increased locomotor activity, are hyper-responsive to nociceptive stimuli, and have increased basal arousal levels, as compared to rats maintained on a normal-protein diet (NP; 20% casein). The present study was performed to determine whether animals on the HP diet display deficits in learning, memory, and sensory discrimination. Male, Sprague-Dawley rats (4 months old) were divided into two groups and fed either the NP diet or the HP diet, ad libitum, for 32 weeks. Then the animals were observed in a variety of behavioral tests. In the swimming cylinder of Porsolt, which tests adaptation to stress, the HP group was significantly less able than the control group to develop an effective coping strategy (p < 0.05). When tested in the Morris Watermaze, animals on both diets performed equally well in the acquisition and recall of spatial information. During the recording of auditory evoked responses to deviant tones, short-term auditory memory traces degraded more quickly in the HP group than in the NP group (p < 0.05). These data suggest that rats fed the HP diet experienced deficits in short-term memory, associated with a diminished ability to cope with acute stress, whereas long-term memory was unaffected. PMID- 27414700 TI - Inositol and Ginkgo biloba as Adjuncts in Chronic Depression: Case Report. AB - The treatment of resistant depression has involved the use of various adjuncts in addition to the antidepressant, such as lithium or liothyronine (T3). This case report describes a woman with a history of chronic depression (dysthymic disorder), unresponsive to a number of traditional antidepressants, who was treated with the antidepressant bupropion and the nutritional and herbal supplements inositol and ginkgo. Her bupropion was able to be reduced, and she appeared to respond well to the added supplements, reducing her Ham-D score from 17 to 11. In this case, it was hypothesized that the inositol was the probable active adjunct with regard to the antidepressant effect, with the ginkgo helping with cognition. The inositol theory is reviewed with reference to mania and depression. PMID- 27414701 TI - Analyzing Data from Experiments in which the Outcome is Time to an Event. AB - This is the third in a series of articles devoted to a simplified description of experimental design, statistical analysis, and interpretation. The present article deals with an overview of time to event methods, the importance of censored information, and the utilization of survival methods with three concrete examples. These methods can be used to design experiments with increased power to detect significant differences. Experiments planned with time to event methods usually have reduced sample size requirements. PMID- 27414702 TI - Clinical experience of unexpected findings in prenatal array testing. AB - AIM: The aim of this study was to evaluate whether unexpected diagnoses (UD) made by prenatal array testing contribute to pregnancy management. PATIENTS & METHODS: In 2010-2015 in 19/4043 (0.5%) pregnancies an UD was made. The clinical usefulness of UDs was assessed based on the couple's responses during post-test counseling and their decisions. RESULTS: In 16/19 cases, the UD was helpful either for the couples in making a decision about the course of their pregnancy, for perinatal management or family genetic counseling. CONCLUSION: The majority of the pregnant couples found the UDs relevant for pregnancy management and genetic counseling. This adds another motive for offering whole genome array during pregnancy in patients who wish broad testing of their fetus. PMID- 27414704 TI - Non-covalent interaction of benzene with methanol and diethyl ether solid surfaces. AB - We present laboratory experiments on binary, layered ices comprised of benzene (C6H6) on methanol (CH3OH) and on diethyl ether (CH3CH2OCH2CH3). Temperature programmed desorption (TPD) and reflection-absorption infrared spectroscopy (RAIRS) have been used to investigate the growth mechanisms in these systems. Ab initio quantum chemical calculations on simple gas-phase model clusters are used to aid interpretation of the experimental data by highlighting the key interactions established at the interface. Our observations are consistent with C6H6 forming islands on CH3OH, although evidence of strong hydrogen bonding interactions indicates some degree of surface wetting. In contrast, layer-by layer growth is proposed for C6H6 on the CH3CH2OCH2CH3 substrate. PMID- 27414703 TI - Feasibility of online self-administered cognitive training in moderate-severe brain injury. AB - PURPOSE: Cognitive environmental enrichment (C-EE) offers promise for offsetting neural decline that is observed in chronic moderate-severe traumatic brain injury (TBI). Brain games are a delivery modality for C-EE that can be self-administered over the Internet without therapist oversight. To date, only one study has examined the feasibility of self-administered brain games in TBI, and the study focused predominantly on mild TBI. Therefore, the primary purpose of the current study was to examine the feasibility of self-administered brain games in moderate severe TBI. A secondary and related purpose was to examine the feasibility of remote monitoring of any C-EE-induced adverse symptoms with a self-administered evaluation tool. METHOD: Ten patients with moderate-severe TBI were asked to complete 12 weeks (60 min/day, five days/week) of online brain games with bi weekly self-evaluation, intended to measure any adverse consequences of cognitive training (e.g., fatigue, eye strain). RESULTS: There was modest weekly adherence (42.6% +/- 4.4%, averaged across patients and weeks) and 70% patient retention; of the seven retained patients, six completed the self-evaluation questionnaire at least once/week for each week of the study. CONCLUSIONS: Even patients with moderate-severe TBI can complete a demanding, online C-EE intervention and a self administered symptom evaluation tool with limited therapist oversight, though at daily rate closer to 30 than 60 min per day. Further self-administered C-EE research is underway in our lab, with more extensive environmental support. Implications for Rehabilitation Online brain games (which may serve as a rehabilitation paradigm that can help offset the neurodegeneration observed in chronic TBI) can be feasibly self-administered by moderate-to-severe TBI patients. Brain games are a promising therapy modality, as they can be accessed by all moderate-to-severe TBI patients irrespective of geographic location, clinic and/or therapist availability, or impairments that limit mobility and access to rehabilitation services. Future efficacy trials that examine the effect of brain games for offsetting neurodegeneration in moderate-to-severe TBI patients are warranted. PMID- 27414705 TI - An Internationally Consented Standard for Nursing Process-Clinical Decision Support Systems in Electronic Health Records. AB - Nurses are accountable to apply the nursing process, which is key for patient care: It is a problem-solving process providing the structure for care plans and documentation. The state-of-the art nursing process is based on classifications that contain standardized concepts, and therefore, it is named Advanced Nursing Process. It contains valid assessments, nursing diagnoses, interventions, and nursing-sensitive patient outcomes. Electronic decision support systems can assist nurses to apply the Advanced Nursing Process. However, nursing decision support systems are missing, and no "gold standard" is available. The study aim is to develop a valid Nursing Process-Clinical Decision Support System Standard to guide future developments of clinical decision support systems. In a multistep approach, a Nursing Process-Clinical Decision Support System Standard with 28 criteria was developed. After pilot testing (N = 29 nurses), the criteria were reduced to 25. The Nursing Process-Clinical Decision Support System Standard was then presented to eight internationally known experts, who performed qualitative interviews according to Mayring. Fourteen categories demonstrate expert consensus on the Nursing Process-Clinical Decision Support System Standard and its content validity. All experts agreed the Advanced Nursing Process should be the centerpiece for the Nursing Process-Clinical Decision Support System and should suggest research-based, predefined nursing diagnoses and correct linkages between diagnoses, evidence-based interventions, and patient outcomes. PMID- 27414708 TI - Problems solutions. PMID- 27414707 TI - Coming in postgraduate medicine. PMID- 27414706 TI - Metal-Organic Framework Coatings as Cytoprotective Exoskeletons for Living Cells. AB - The biomimetic mineralization of metal-organic framework (MOF) material on living cells is reported. ZIF-8 can be crystallized on a living cell surface as an exoskeleton that offers physical protection while allowing transport of essential nutrients, thus maintaining cell viability. The MOF shell prevents cell division, leading to an artificially induced pseudo-hibernation state. Cellular functions can be fully restored upon MOF removal. PMID- 27414710 TI - What's happening in medicine. PMID- 27414709 TI - Washington Background. PMID- 27414711 TI - Self-Test On Infection Control. PMID- 27414712 TI - ReadySource on Infection Control. PMID- 27414713 TI - Pituitary Failure with Normal Skull X-Ray Films. PMID- 27414715 TI - 1975 Interstate Postgraduate Medical Assembly Program. PMID- 27414716 TI - Therapeutic Index to Advertisers. PMID- 27414717 TI - Endoscopic/Endobronchial Ultrasound-Guided Fine Needle Aspiration and Ancillary Techniques, Particularly Flow Cytometry, in Diagnosing Deep-Seated Lymphomas. AB - Evaluation of deep-seated lymphomas by fine-needle aspiration (FNA) can be challenging due to their reduced accessibility. Controversy remains as to whether FNA and ancillary techniques can be used to diagnose deep-seated lymphomas reliably and sufficiently for clinical management. Most published studies are favorable that endobronchial ultrasound (EBUS)/endoscopic ultrasound (EUS)-FNA plays an important role in the diagnosis of deep-seated lymphomas. The addition of ancillary techniques, particularly flow cytometry, increases diagnostic yield. While subclassification is possible in a reasonable proportion of cases, the reported rates of successful subclassification are lower than those for lymphoma detection/diagnosis. The diagnostic limitation exists for Hodgkin's lymphoma, grading of follicular lymphoma, and some T-cell lymphomas. The role of FNA in deep-seated lymphomas is much better established for recurrent than primary disease. It remains unclear whether the use of large-sized-needle FNA or a combination of core needle biopsy and FNA improves subclassification. It is important for cytopathologists to have considerable understanding of the WHO lymphoma classification and develop a collaborative working relationship with hematopathologists and oncologists. As EUS/EBUS-FNA techniques advance and sophisticated molecular techniques such as next- generation sequencing become possible, the role of FNA in the diagnosis of deep-seated lymphomas will possibly increase. PMID- 27414718 TI - Electrostatic Interaction-Induced Room-Temperature Phosphorescence in Pure Organic Molecules from QM/MM Calculations. AB - Room temperature phosphorescence (RTP) from pure organic material is rare due to the low phosphorescence quantum efficiency. That is why the recent discovery of crystallization induced RTP for several organic molecules aroused strong interests. Through a combined quantum and molecular mechanics CASPT2/AMBER scheme taking terephthalic acid (TPA) as example, we found that electrostatic interaction not only can induce an enhanced radiative decay T1 -> S0 through the dipole-allowed S1 intermediate state, but also can hinder the nonradiative decay process upon crystallization. From gas phase to crystal, the nature of S1 state is converted to (1)(pi,pi*) from (1)(n,pi*) character, enhancing transition dipole moment and serving as an efficient intermediate radiative pathway for T1 > S0 transition, and eventually leading to a boosted RTP. The intermolecular packing also blocks the nonradiative decay channel of the high-frequency C?O stretching vibration with large vibronic coupling, rather than the conventional low-frequency aromatic rotation in crystal. This mechanism also holds for other organic compounds that contain both ketones and aromatic rings. PMID- 27414719 TI - Micro and nanotechnologies in heart valve tissue engineering. AB - Due to the increased morbidity and mortality resulting from heart valve diseases, there is a growing demand for off-the-shelf implantable tissue engineered heart valves (TEHVs). Despite the significant progress in recent years in improving the design and performance of TEHV constructs, viable and functional human implantable TEHV constructs have remained elusive. The recent advances in micro and nanoscale technologies including the microfabrication, nano-microfiber based scaffolds preparation, 3D cell encapsulated hydrogels preparation, microfluidic, micro-bioreactors, nano-microscale biosensors as well as the computational methods and models for simulation of biological tissues have increased the potential for realizing viable, functional and implantable TEHV constructs. In this review, we aim to present an overview of the importance and recent advances in micro and nano-scale technologies for the development of TEHV constructs. PMID- 27414721 TI - Surfactant protein B: From biochemistry to its potential role as diagnostic and prognostic marker in heart failure. AB - Growing interest raised on circulating biomarkers of structural alveolar capillary unit damage and very recent data support surfactant protein type B (SP B) as the most promising candidate in this setting. With respect to other proteins proposed as possible markers of lung damage, SP-B has some unique qualities: it is critical for the assembly of pulmonary surfactant, making its lack incompatible with life; it has no other known site of synthesis except alveolar epithelial cells different from other surfactant proteins; and, it undergoes a proteolytic processing in a pulmonary-cell-specific manner. In the recent years circulating SP-B isoforms, mature or immature, have been demonstrated to be detectable in the circulation depending on the magnitude of the damage of alveolar capillary membrane. In the present review, we summarize the recent knowledge on SP-B regulation, function and we discuss its potential role as reliable biological marker of alveolar capillary membrane (dys)function in the context of heart failure. PMID- 27414720 TI - Magnitude of QRS duration reduction after biventricular pacing identifies responders to cardiac resynchronization therapy. AB - BACKGROUND: Several studies have investigated the association between native QRS duration (QRSd) or QRS narrowing and response to biventricular pacing. However, their results have been conflicting. The aim of our study was to determine the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who undergo cardiac resynchronization therapy (CRT) implantation. METHODS AND RESULTS: We included 311 patients in whom a CRT device was implanted in accordance with current guidelines for CRT. On implantation, the native QRS, the QRSd and the QI during CRT were measured. After 6months, 220 (71%) patients showed a 10% reduction in LVESV. The median [25th 75th] QI was 14.3% [7.2-21.4] and was significantly related to reverse remodeling (r=+0.22; 95%CI: 0.11-0.32, p=0.0001). The cut-off value of QI that best predicted LV reverse remodeling after 6months of CRT was 12.5% (sensitivity=63.6%, specificity=57.1%, area under the curve=0.633, p=0.0002). The time to the event death or cardiovascular hospitalization was significantly longer among patients with QI>12.5% (log-rank test, p=0.0155), with a hazard ratio (HR) of 0.3 [95%CI: 0.11-0.78]. In the multivariate regression model adjusted for baseline parameters, a 10% increment in QI (HR=0.61[0.44-0.83], p=0.002) remained significantly associated with CRT response. CONCLUSIONS: Patients with a larger decrease in QRSd after CRT initiation showed greater echocardiographic reverse remodeling and better outcome from death or cardiovascular hospitalization. QI is an easy-to-measure variable that could be used to predict CRT response at the time of pacing site selection or pacing configuration programming. PMID- 27414722 TI - Impact of comorbidity and basal health status on coronary care unit admission and clinical profile in nonagenarians with acute myocardial infarction. PMID- 27414723 TI - Using a steerable guiding sheath to implant an AMPLATZERTMAmuletTM Left Atrial Appendage Occluder for prevention of thromboembolic stroke. PMID- 27414724 TI - Multimodality imaging in cardiac echinococcosis for diagnosis and follow-up of an untreatable cyst. PMID- 27414725 TI - Differential effect of side branch intervention on long-term clinical outcomes according to side branch stenosis after main vessel stenting: Results from the COBIS (Coronary Bifurcation Stenting) Registry II. AB - BACKGROUND: Indication of side branch (SB) intervention after main vessel (MV) stenting is not established for coronary bifurcation lesions. METHODS: We evaluated 2017 patients who were treated with 1-stent technique or MV stenting as a first strategy. Patients undergoing SB intervention after MV stenting (SB intervention group, n=929) were compared to those treated with MV stenting only (no-SB intervention group, n=1088). RESULTS: During a median follow-up of 37months, cardiac death or myocardial infarction (MI) tended to occur less frequently in the SB intervention group than in the no-SB intervention group (1.8% versus 2.9%; adjusted hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.25-1.11; P=0.09). There was a significant interaction between SB intervention and SB stenosis after MV stenting (P for interaction <0.01). Among 1077 patients with diameter stenosis of SB >=50% after MV stenting, SB intervention was associated with a lower risk of cardiac death or MI (1.2% versus 4.2%; adjusted HR 0.22; 95% CI 0.09-0.52; P<0.01). However, among 940 patients with diameter stenosis of SB <50%, there was no significant difference in cardiac death or MI between the SB intervention group and the no-SB intervention group (3.5% versus 2.2%; adjusted HR 1.36; 95% CI 0.58-3.20; P=0.48). CONCLUSIONS: The effect of SB intervention differed according to SB stenosis after MV stenting. SB intervention may reduce cardiac death or MI in bifurcation lesions with diameter stenosis of SB >=50% after MV stenting. PMID- 27414726 TI - Is cystatin C an evaluative marker for right heart functions in systemic sclerosis? PMID- 27414727 TI - Association between diabetes and prevalence and growth rate of abdominal aortic aneurysms: A meta-analysis. AB - BACKGROUND: Although the prevalence of abdominal aortic aneurysm (AAA) was lower in diabetes, the relationship between diabetes and AAA prevalence remains unclear. In this meta-analysis, we sought to clarify the effect of diabetes on prevalence and growth rate (GR) of AAA. METHODS: We searched PubMed, Web of Science, Scopus and Cochrane databases. Articles reporting the AAA prevalence in diabetic patients and diabetic effects in GR of AAA were included. RESULTS: Forty nine studies on AAA prevalence in diabetics and thirteen studies on effect of diabetes in GR of AAA were included for meta-analysis. A strongly negative association was found between diabetes and AAA prevalence in population based screening (odds ratio [OR]adjusted: 0.66; 95% confidence interval [CI]: 0.58 0.75) and prospective studies (ORadjusted: 0.52; 95% CI: 0.43-0.63), but not in case-control studies (ORadjusted: 0.48; 95% CI: 0.20-1.15). Similar association was found in North American (ORadjusted: 0.62; 95% CI 0.54-0.71) and European (ORadjusted: 0.45; 95% CI 0.33-0.62) studies. The strongly negative association remained consistent after stratification by time of data collection (up to -1995 [ORadjusted: 0.65; 95% CI: 0.53-0.80], 1996-2005 [ORadjusted: 0.61; 95% CI: 0.47 0.78], 2006 and beyond- [ORadjusted: 0.67; 95% CI: 0.53-0.85], and data collection time >10years [ORadjusted: OR: 0.44; 95% CI 0.34-0.58]). The annual mean diabetic effect on AAA GR was -0.60mm/y (95% CI: -0.76 - -0.43). CONCLUSION: Diabetes was strongly and negatively associated with AAA prevalence regardless of study type, geography and time of data collection, as well as negative impact of diabetes on GR of AAA. PMID- 27414728 TI - Acute left ventricular dilatation after herbal weight loss tea usage. PMID- 27414729 TI - Focal fibrosis and diffuse fibrosis are predictors of reversed left ventricular remodeling in patients with non-ischemic cardiomyopathy. AB - BACKGROUND: Prognostic value of myocardial fibrosis in patients with non-ischemic idiopathic dilated cardiomyopathy (DCM) is not well-defined. We sought to assess the association of focal and diffuse myocardial fibrosis with left ventricular reversed remodeling (LVRR). METHODS: Patients with DCM who underwent cardiac MRI with baseline and subsequent follow-up echocardiography were included in the study. Post-contrast T1 times were corrected for renal function, body size, gadolinium dose and time after Gadolinium injection. Patients were followed over a median time of 29months to evaluate changes of left ventricular end-systolic volume (LVESV). A Linear Mixed Model was used to assess the relationship between the LVESV during follow-up, corrected post-T1 value delayed hyperenhancement (DHE), and modified Seattle Heart Failure Score (SHFS). RESULTS: A total of 103 patients (mean age 51+/-15years, 61% male) were evaluated. The mean LVEF was 33+/ 11%, LVESVi 62+/-39ml/m(2), and T1 time 416+/-98. DHE was identified in 45 patients (44%). Patients with focal DHE (n=45) had higher LVESVi at baseline and during follow-up (p=0.024). Post T1 value >450 was an independent predictor of LVRR at the follow-up (Delta=24.6ml/m(2) SE 14.6ml/2, p=0.0480) in patients despite the presence of DHE, even after adjusting for their SHFS. CONCLUSION: While DCM patients with focal DHE demonstrated greater adverse LV remodeling than those without focal fibrosis, diffuse fibrosis independently predicts LVRR in DCM patients in patients despite the presence of focal fibrosis. PMID- 27414730 TI - The effect of serum potassium level on in-hospital and long-term mortality in ST elevation myocardial infarction. AB - Current studies evaluating the effect of serum potassium levels on mortality in patients with ST elevation myocardial infarction (STEMI) are lacking. We analyzed retrospectively 3760 patients diagnosed with STEMI. Mean serum potassium levels were categorized accordingly: <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, 5.0 to <5.5, and >=5.5mEq/L. The lowest mortality was determined in patients with serum potassium level of 4 to <4.5mEq/L whereas mortality was higher in patients with serum potassium levels of >=5.0 and <3.5mEq/L. In a multivariable Cox-proportional regression analysis, the mortality risk was higher for patients with serum potassium levels of >=5mEq/L [hazard ratio (HR), 2.11; 95% confidence interval (CI) 1.23-4.74 and HR, 4.20; 95% CI 1.08-8.23, for patients with potassium levels of 5 to <5.5mEq/L and >=5.5mEq/L, respectively]. In-hospital and long-term mortality risks were also higher for patients with serum potassium levels of <=3.5mEq/L. Conversely, ventricular arrhythmias were higher only for patients with serum potassium level of <=3.5mEq/L. Furthermore, a significant relationship was found between the patient with serum potassium levels of <=3.5mEq/L and ventricular arrhythmias. PMID- 27414731 TI - Hazards of interpreting the late results on durability of bioprosthetic valves. Cautions & suggestions. PMID- 27414732 TI - Simple predictors for new onset atrial fibrillation. AB - BACKGROUND: Predicting atrial fibrillation is a tremendous challenge. Only few studies have included 24h-Holter monitoring characteristics to predict new onset AF (NOAF). OBJECTIVES: Our aim is to define simple predictors for NOAF. METHODS: The study population included 468 patients undergoing Holter for any cause. After excluding 169 patients for history of AF prior to or during the Holter monitoring period, 299 patients were assessed for incidence of NOAF. RESULTS: Age at inclusion was 62.5+/-18years (53.5% male). After a median follow up of 39.1 [IQI 36.6-40] months, the incidence of NOAF was 10.4%. With univariate analysis, age, hypertension, diabetes, renal impairment, heart failure/cardiomyopathy, left ventricle ejection fraction <=50%, left atrium diameter >=40mm, CHA2DS2 VASc >=4, premature atrial complexes (PAC) >=0.2%, and PR interval were associated with NOAF. With multivariate analysis, age (HR 1075; p=0.001 per year), presence of heart failure/cardiomyopathy (HR 6,16; p<0.001), PAC>=0.2% (HR 3,32; p=0.003) and PR interval (HR 1.011; p=0.006 per millisecond) were independent predictors for NOAF. Those predictors were used to create a risk calculator for NOAF, which was validated in an independent cohort of 200 consecutive patients with similar baseline characteristics. This new tool resulted in good discrimination capacity calculated by the C index for NOAF prediction: Area under curve (AUC) (95% CI) 0.794 (0.714-0.875) at 2years and 0.794 (0.713-0.875) at 3years. CONCLUSIONS: Simple clinical, ECG and Holter monitoring parameters are able to predict NOAF in a broad population and may help guide more rigorous monitoring for atrial fibrillation. PMID- 27414733 TI - Depressive symptom severity and mortality in older adults undergoing percutaneous coronary intervention. PMID- 27414734 TI - QRS duration and left ventricular ejection fraction (LVEF) in non-ST segment elevation myocardial infarction (NSTEMI). AB - BACKGROUND: Non-traditional EKG parameters such as QRS pattern and QRS duration (QRSd) are being investigated in acute coronary syndrome as prognostic markers. Following an infarction, the heart attempts to compensate for myocardial loss through remodeling which eventually lowers the ejection fraction (LVEF). Our objective is to evaluate the relationship between the QRSd at the time of NSTEMI and extent of coronary artery disease (CAD) and changes in LVEF. METHODS AND RESULTS: Patients admitted with NSTEMI between 08/01/2006 and 9/30/2012 were included. Patients were classified into high or low QRSd at cutoff value of 90ms noted on initial EKG after excluding bundle-branch block. A total of 536 patients with mean age of 66+/-14years were included. 49% were male and majority were African American (73%). Patients within the higher QRSd group had a lower LVEF at the time of the NSTEMI compared to those with QRSd <90ms (47+/-15% vs. 50+/-13%; p<0.038). The LVEF remained lower in the high QRS group on follow up to 12months (47+/-15% vs. 52+/-11%; p<0.001). The high QRSd group had a higher incidence of severe LV dysfunction at baseline (27% vs. 18%; p<0.045). Logistic regression analysis revealed that a QRSd >=90ms was also independently associated with a severely reduced LVEF on follow-up (OR=2.7; CI 1.55-4.69; p<0.001). CONCLUSION: QRSd >=90ms at the time of NSTEMI is predictive of three-vessel/left main coronary artery involvement and a lower LVEF. This depression in LVEF is maintained for up to 12months. Thus, the QRSd at time of NSTEMI has additional prognostic significance. PMID- 27414735 TI - Gap junction modifiers regulate electrical activities of the sinoatrial node and pulmonary vein: Therapeutic implications in atrial arrhythmogenesis. AB - BACKGROUND: Gap junction (GJ) dysfunctions predispose cardiac tissues to various arrhythmias. Sinoatrial node (SAN) and pulmonary veins (PVs) are closely related atrial dysrhythmia. This study evaluated whether GJ modifications modulate SAN and PVs electrical activities. METHODS: Conventional microelectrodes were used to record action potentials in isolated rabbit SAN, PVs, and connected PV-SAN tissue preparations before and after heptanol (GJ inhibitor) and PQ1 (GJ enhancer) administration with and without isoproterenol. A whole-cell patch clamp was used to record the electrical activities before and after heptanol in single SAN and PV cardiomyocytes. RESULTS: Heptanol (1, 3, and 10MUM) reduced the spontaneous beating rates of isolated SAN preparations but not PVs. Heptanol (10MUM) decelerated the SAN leading rhythm in the PV-SAN preparations and induced PV burst firings without (3 of 6, 50%) and with (6 of 6, 100%) isoproterenol (1MUM). Heptanol (10MUM) also reduced the spontaneous beating rates in single SAN cardiomyocyte, but not PV cardiomyocyte, with a decreased pacemaker current. PQ1 (50 and 500nM) treatment did not change the spontaneous beating rates in isolated SAN and PV preparations. In the connected PV-SAN preparations, PQ1 (500nM) did not induce any PV firing even having additional isoproterenol treatment (1MUM). Moreover, PQ1 (500nM) prevented heptanol-induced electrical changes in SAN and PVs preparations. CONCLUSION: GJ dysfunction modulates SAN and PV electrical activity, which may contribute to atrial arrhythmogenesis. GJ enhancer has a therapeutic potential in SAN dysfunction and atrial arrhythmogenesis. PMID- 27414736 TI - Prognostic value of an abnormal response to acetylcholine in patients with angina and non-obstructive coronary artery disease: Long-term follow-up of the Heart Quest cohort. AB - BACKGROUND: This study aims to determine whether small vessel disease (SVD) or vasospastic disease (VSD) has an impact on prognosis. METHODS: The prospective cohort embraced 718 patients with angina equivalent symptoms and no coronary stenosis >=50% recruited between 1997 and 2008. At baseline, patients were classified as having SVD, VSD, other cardiac disease or non-cardiac problem based on intracoronary acetylcholine application and fast atrial pacing during coronary angiography. Patients underwent follow-up between 2007 and 2015. Prognostic significance of the diagnosis on cardiovascular events (cardiovascular death or non-fatal myocardial infarction) was evaluated using Cox proportional hazards models adjusted for age and sex. RESULTS: The mean follow-up duration was 11.3+/ 2.7years. Only 11 patients (1.5%) were lost to follow-up, resulting in an analyzed population of 707 patients. Patients with SVD (HR: 4.9, 95% CI: 1.1 22.4, P=0.040) and VSD (HR: 4.8, 95% CI: 1.0-23.4, P=0.050) had an increased risk of suffering cardiovascular events compared to patients with non-cardiac problems. Among SVD patients, those with the presence of endothelial dysfunction had a particularly high risk (HR: 7.3, 95% CI: 1.5-35.5, P=0.015). Among patients with SVD or VSD, those having persisting or worsening angina during follow-up had a higher risk than patients in whom angina improved (HR: 4.8, 95% CI: 1.9-12.3, P=0.001). CONCLUSIONS: Our study shows that patients with SVD or VSD have an increased risk of cardiovascular events. This particularly applies to SVD patients with endothelial dysfunction. Symptoms should be taken seriously in SVD and VSD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01318629. PMID- 27414737 TI - Cardiac resynchronization therapy reduces left ventricular energy loss. PMID- 27414738 TI - Right ventricular systolic function as a marker of prognosis after ST-elevation inferior myocardial infarction 5-year follow-up. AB - BACKGROUND: There is scarce data about clinical value of right ventricular (RV) systolic function assessed in pre-discharge transthoracic echocardiography for predicting long-term prognosis in patients with inferior ST-elevation myocardial infarction (MI). METHODS: The aim of this study was to assess correlations of RV function parameters in patients after inferior ST-elevation MI with preserved or mildly impaired left ventricular ejection fraction with prognosis during 5-year follow-up. Primary endpoint was death from any cause or unscheduled hospitalization for cardiac causes (unstable angina/MI, percutaneous coronary intervention/coronary artery bypass grafting due to progression of coronary artery disease, heart failure exacerbation or pacemaker implantation), secondary endpoints were all listed above components analyzed separately. RV systolic function was measured with pulsed tissue Doppler as systolic myocardial velocity at the basal segment of RV free wall in the acute phase and pre-discharge echocardiography. RESULTS: Follow-up was conducted in 86 consecutive patients (mean age 61+/-10years, 74% males). Multivariate regression analysis revealed that only RV systolic function in pre-discharge echocardiography correlated independently with the primary endpoint (OR 0.56, 95% CI 0.34-0.92, p=0.02). A positive predictive value of 44% and a negative predictive value of 83% (sensitivity 80%, specificity 49%, AUC 0.7) for predicting the primary endpoint was established for RV systolic myocardial velocity<13cm/s in pre-discharge echocardiography. CONCLUSIONS: In patients after inferior wall ST-elevation MI with preserved or slightly impaired LV systolic function, pre-discharge RV systolic dysfunction correlated independently with worse long-term prognosis. PMID- 27414739 TI - -759C>T Polymorphism of the HTR2C Gene is Associated with Second Generation Antipsychotic-Induced Weight Gain in Female Patients with Schizophrenia. AB - Introduction: The HTR2C gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the association between -759C>T, functional polymorphism of the HTR2C receptor, and AIWG. Methods: A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated. Patients were weighted at admission and again at 6 weeks of hospitalization. Weight gain was defined as an increase>=7% of baseline weight. The association between polymorphisms HTR2C and weight gain was evaluated. Multiple logistic regression was run to determine potential confounders. Results: Patients with the T allele at position -759 (TT or CT) gained less weight as compared to patients who did not have the allele. This association was not affected by possible confounding factors such as age, baseline BMI, and prior psychopharmacological treatment. Discussion: The T allele at position -759 protects against AIWG in female patients with schizophrenia. PMID- 27414740 TI - Use of Paliperidone Palmitate Throughout a Schizoaffective Disorder Patient's Gestation Period. AB - Introduction: Paliperidone palmitate treatment of schizophrenia or schizoaffective disorder is effective and well tolerated, but there is almost no data on its safety during pregnancy. Case report: An analysis is made of the safety and tolerability of paliperidone palmitate treatment throughout the gestation period in a 34-year-old patient diagnosed with schizoaffective disorder. Discussion: Paliperidone palmitate treatment throughout the gestation period was safe and well tolerated by both mother and foetus, there being no malformations or other perinatal complications in the newborn to date. PMID- 27414741 TI - ROS-mediated apoptosis of HAPI microglia through p53 signaling following PFOS exposure. AB - Perfluorooctane sulfonate (PFOS), the most extensively studied member of perfluoroalkyl and polyfluoroalkyl substances (PFASs), has been thought to be toxic to the central nervous system (CNS) of mammals. However, the neurotoxic effects of PFOS remain largely unknown. In this study, the effect of PFOS on microglial apoptosis was examined. The results showed that PFOS could significantly reduce the cell viability and mediate cell apoptosis in HAPI microglia, which was closely accompanied with ROS production and p53 overexpression. Moreover, p53 interference significantly ameliorated PFOS triggered cytotoxic effects in HAPI microglia, including the downregulation of cleaved PARP and cleaved caspase 3. Interestingly, NAC, a ROS inhibitor, inhibited p53 expression, and decreased the apoptosis of HAPI microglia. Taken together, these findings suggest that upregulated production of ROS plays a vital role in PFOS-mediated apoptosis in HAPI microglia via the modulation of p53 signaling. PMID- 27414742 TI - Cerebral ganglion ultrastructure and differential proteins revealed using proteomics in the aplysiid (Notarcus leachii cirrosus Stimpson) under cadmium and lead stress. AB - Cadmium (Cd) and lead (Pb) are both highly toxic metals in environments. However the toxicological mechanism is not clear. In this study, the aplysiid, Notarcus leachii cirrosus Stimpson (NLCS) was subjected to Cd (NLCS-Cd) or Pb (NLCS-Pb). The cerebral ganglion of NLCS was investigated with a transmission electron microscope. Next the differential proteins were separated and identified using proteomic approaches. Eighteen protein spots in NLCS-Cd and seventeen protein spots in NLCS-Pb were observed to be significantly changed. These protein spots were further excised in gels and identified. A hypothetical pathway was drawn to show the correlation between the partially identified proteins. The results indicated that damage to the cerebral ganglion was follows: cell apoptosis, lysosomes proliferation, cytoskeleton disruption, and oxidative stress. These phenomena and data indicated potential biomarkers for evaluating the contamination levels of Cd and Pb. This study provided positive insights into the mechanisms of Cd and Pb toxicity. PMID- 27414743 TI - Genetic polymorphisms study of pharmacogenomic VIP variants in Han ethnic of China's Shaanxi province. AB - BACKGROUND: Multiple factors include genetic and non-genetic interactions induce to different drug response among different individuals. Lots of researches proved that different frequencies of genetic variants exists different ethnic groups. The aim of this study was to screen Han volunteers in Shaanxi for VIP gene polymorphisms. MATERIALS AND METHODS: We genotyped 80 Very Important Pharmacogenes (VIP) (selected from the PharmGKB database) in 192 unrelated, healthy Han ethnic adults from Shaanxi, the northwest of China, and then analyzed genotyping data wtih Structure and F-statistics (Fst) analysis. RESULTS: We compared our data with 15 other populations (Deng, Kyrgyz, Tajik, Uygur and 11 HapMap populations), and found the frequency distribution of Han population in Shaanxi is most similar with CHB. Also, Structure and Fst showed that Shaanxi Han has a closest genetic background with CHB. CONCLUSIONS: Our study have supplemented the Han Chinese data related to pharmacogenomics and illustrated differences in genotypic frequencies of selected VIP variants' among the Han population and 15 other populations. PMID- 27414744 TI - Ewes With Divergent Cortisol Responses to ACTH Exhibit Functional Differences in the Hypothalamo-Pituitary-Adrenal (HPA) Axis. AB - Within any population, the cortisol response to ACTH covers a considerable range. High responders (HRs) exhibit a greater cortisol secretory response to stress or ACTH, compared with individuals classified as low cortisol responders (LRs). We administered ACTH (0.2 MUg/kg, iv) to 160 female sheep and selected subpopulations of animals as LR and HR. In the present study, we aimed to characterize the hypothalamo-pituitary-adrenal axis in HR and LR and to identify factors that underlie the differing cortisol responses to ACTH. Hypothalami, pituitaries, and adrenals were collected from nonstressed HR and LR ewes. Expression of genes for CRH, arginine vasopressin (AVP), oxytocin, glucocorticoid receptor, and mineralocorticoid receptor were measured by in situ hybridization in the paraventricular nucleus of the hypothalamus, and proopiomelanocortin (POMC) gene expression was measured in the anterior pituitary. Expression of CRH, AVP, and POMC was higher in HR, with no differences in either glucocorticoid receptor or mineralocorticoid receptor expression. Oxytocin expression was greater in LR. In the adrenal gland, real-time PCR analysis indicated that expression of the ACTH receptor and a range of steroidogenic enzymes was similar in HR and LR. Adrenal weights, the cortex to medulla ratio and adrenal cortisol content were also similar in LR and HR. In conclusion, LR and HR display innate differences in the steady-state expression of CRH, AVP, oxytocin, and POMC, indicating that selection for cortisol responsiveness identifies distinct subpopulations that exhibit innate differences in the gene expression/function of hypothalamo-pituitary-adrenal axis markers. PMID- 27414745 TI - KIF5A de novo mutation associated with myoclonic seizures and neonatal onset progressive leukoencephalopathy. AB - The KIF5A gene (OMIM 602821) encodes a neuron-specific kinesin heavy chain involved in intracellular transport of mitochondria and other cargoes. KIF5A protein comprises the N terminal motor domain, the stalk domain and the C terminal cargo binding domain. The binding between KIF5A and its cargoes is mediated by kinesin adaptor proteins such as TRAK1 and TRAK2. Numerous missense KIF5A mutations in the motor and stalk domains cause spastic paraplegia type 10 (SPG10, OMIM 604187). Conversely, the role of loss-of-function mutations, especially those affecting the cargo binding domain, is unclear. We describe a novel de novo KIF5A p.Ser974fs/c.2921delC mutation found by whole exome sequencing in a patient with a congenital severe disease characterized by myoclonic seizures and progressive leukoencephalopathy. Since this phenotype differs considerably from the KIF5A/SPG10 disease spectrum we propose that the KIF5A p.Ser974fs and possibly other mutations which lead to truncation of the C terminal tail of the protein cause a novel disorder. We speculate that the unique effect of the C-terminal truncating KIF5A mutations may result from the previously described complex role of this protein domain in binding of the TRAK2 and possibly other kinesin adaptor protein(s). PMID- 27414746 TI - A review of the perceptual effects of hearing loss for frequencies above 3 kHz. AB - BACKGROUND: Hearing loss caused by exposure to intense sounds usually has its greatest effects on audiometric thresholds at 4 and 6 kHz. However, in several countries compensation for occupational noise-induced hearing loss is calculated using the average of audiometric thresholds for selected frequencies up to 3 kHz, based on the implicit assumption that hearing loss for frequencies above 3 kHz has no material adverse consequences. This paper assesses whether this assumption is correct. DESIGN: Studies are reviewed that evaluate the role of hearing for frequencies above 3 kHz. RESULTS: Several studies show that frequencies above 3 kHz are important for the perception of speech, especially when background sounds are present. Hearing at high frequencies is also important for sound localization, especially for resolving front-back confusions. CONCLUSIONS: Hearing for frequencies above 3 kHz is important for the ability to understand speech in background sounds and for the ability to localize sounds. The audiometric threshold at 4 kHz and perhaps 6 kHz should be taken into account when assessing hearing in a medico-legal context. PMID- 27414747 TI - Synthesis and biological activity of a new class of insecticides: the N-(5-aryl 1,3,4-thiadiazol-2-yl)amides. AB - BACKGROUND: Optimization studies on a high-throughput screening (HTS) hit led to the discovery of a series of N-(6-arylpyridazin-3-yl)amides with insecticidal activity. It was hypothesized that the isosteric replacement of the pyridazine ring with a 1,3,4-thiadiazole ring could lead to more potent biological activity and/or a broader sap-feeding pest spectrum. The resulting N-(5-aryl-1,3,4 thiadiazol-2-yl)amides were explored as a new class of insecticides. RESULTS: Several methods for 2-amino-1,3,4-thiadiazole synthesis were used for the preparation of key synthetic intermediates. Subsequent coupling to variously substituted carboxylic acid building blocks furnished the final targets, which were tested for insecticidal activity against susceptible strains of Aphis gossypii (Glover) (cotton aphid), Myzus persicae (Sulzer) (green peach aphid) and Bemisia tabaci (Gennadius) (sweetpotato whitefly). CONCLUSION: Structure-activity relationship (SAR) studies on both the amide tail and the aryl A-ring of novel N (5-aryl-1,3,4-thiadiazol-2-yl)amides led to a new class of insecticidal molecules active against sap-feeding insect pests. (c) 2016 Society of Chemical Industry. PMID- 27414748 TI - Current viewpoints on DSM-5 in Japan. AB - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, and its official Japanese version was published in 2014. The Japanese Government uses classifications from the 10th revision of the I nternational C lassification of D iseases (ICD-10) to categorize disorders and determine treatment fees. However, since the publication of the DSM-III, the use of the DSM system has become prevalent in research and educational settings in Japan. In addition to traditional psychiatry, both the ICD and the DSM are taught by many Japanese medical schools, and virtually all clinical research and trials refer to the DSM to define targeted disorders. Amid the current backdrop in which the reputation of the DSM-5 is being established, the editorial board of P sychiatry and C linical N eurosciences has asked Japanese experts across 12 specialties to examine the structure of the DSM-5, including the following categories: Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders, Major Depression, Bipolar Disorders, Obsessive-Compulsive Disorders, Somatic Symptom Disorder, Eating Disorders, Substance-Related and Addictive Disorders, Gender Dysphoria, and Neurocognitive Disorders. Although opinions were only obtained from these selected experts, we believe that we have succeeded, to a certain extent, in presenting views that are representative of each specialty. PMID- 27414750 TI - Halogen Radical Chemistry at Aqueous Interfaces. AB - Halogens play key roles in the chemical composition of marine boundary layers, the free troposphere and the stratosphere. Atmospheric halogen chemistry is dominated by reactions between gas-phase and aqueous species on the surfaces of the ocean and marine aerosol. The mechanisms of interfacial halogen radical/halide reactions, however, are not fully understood, partly due to the dearth of techniques for in situ monitoring of the products and intermediates of fast interfacial halogen radical reactions. Here, we report the online electrospray mass spectrometric identification of the species produced on the surface of aqueous Br(-) and I(-) microjets collided by I(*)(g) pulses generated from the 266 nm laser photolysis of CH3I/O2/N2 gas mixtures. Mass-specific identification of intermediates and products in D2O and H2(18)O solutions and their dependences on I(*)(g) fluxes let us outline mechanisms of formation. We found that the uptake of I(*)(g) on the surface of Br(-) and I(-) microjets (effective uptake coefficient gammaeff >= 2 * 10(-4)) yields IBr(*)(-)/I2(*)(-) radical intermediates, which rapidly react with additional I(*) to produce trihalides I2Br(-)/IBr2(-)/I3(-) plus I3On(-) (n = 1, 2) species within ~10 MUs. Our findings point to a new halogen activation pathway initiated by photogenerated I(*). PMID- 27414749 TI - A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate. AB - Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1 (13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data. PMID- 27414751 TI - Substantial Humic Acid Adsorption to Activated Carbon Air Cathodes Produces a Small Reduction in Catalytic Activity. AB - Long-term operation of microbial fuel cells (MFCs) can result in substantial degradation of activated carbon (AC) air-cathode performance. To examine a possible role in fouling from organic matter in water, cathodes were exposed to high concentrations of humic acids (HA). Cathodes treated with 100 mg L(-1) HA exhibited no significant change in performance. Exposure to 1000 mg L(-1) HA decreased the maximum power density by 14% (from 1310 +/- 30 mW m(-2) to 1130 +/- 30 mW m(-2)). Pore blocking was the main mechanism as the total surface area of the AC decreased by 12%. Minimization of external mass transfer resistances using a rotating disk electrode exhibited only a 5% reduction in current, indicating about half the impact of HA adsorption was associated with external mass transfer resistance and the remainder was due to internal resistances. Rinsing the cathodes with deionized water did not restore cathode performance. These results demonstrated that HA could contribute to cathode fouling, but the extent of power reduction was relatively small in comparison to large mass of humics adsorbed. Other factors, such as biopolymer attachment, or salt precipitation, are therefore likely more important contributors to long-term fouling of MFC cathodes. PMID- 27414752 TI - Extracavitary primary effusion lymphoma associated with hemophagocytic lymphohistiocytosis. PMID- 27414753 TI - The current status and future directions of e-learning in medical education in Korea. PMID- 27414754 TI - The mitochondrial DNA makeup of Romanians: A forensic mtDNA control region database and phylogenetic characterization. AB - To evaluate the pattern of Romanian population from a mitochondrial perspective and to establish an appropriate mtDNA forensic database, we generated a high quality mtDNA control region dataset from 407 Romanian subjects belonging to four major historical regions: Moldavia, Transylvania, Wallachia and Dobruja. The entire control region (CR) was analyzed by Sanger-type sequencing assays and the resulting 306 different haplotypes were classified into haplogroups according to the most updated mtDNA phylogeny. The Romanian gene pool is mainly composed of West Eurasian lineages H (31.7%), U (12.8%), J (10.8%), R (10.1%), T (9.1%), N (8.1%), HV (5.4%),K (3.7%), HV0 (4.2%), with exceptions of East Asian haplogroup M (3.4%) and African haplogroup L (0.7%). The pattern of mtDNA variation observed in this study indicates that the mitochondrial DNA pool is geographically homogeneous across Romania and that the haplogroup composition reveals signals of admixture of populations of different origin. The PCA scatterplot supported this scenario, with Romania located in southeastern Europe area, close to Bulgaria and Hungary, and as a borderland with respect to east Mediterranean and other eastern European countries. High haplotype diversity (0.993) and nucleotide diversity indices (0.00838+/-0.00426), together with low random match probability (0.0087) suggest the usefulness of this control region dataset as a forensic database in routine forensic mtDNA analysis and in the investigation of maternal genetic lineages in the Romanian population. PMID- 27414755 TI - Reduced Crystallization Temperature Methodology for Polymer Selection in Amorphous Solid Dispersions: Stability Perspective. AB - API-polymer interactions, used to select the right polymeric matrix with an aim to stabilize an amorphous dispersion, are routinely studied using spectroscopic and/or calorimetric techniques (i.e., melting point depression). An alternate selection tool has been explored to rank order polymers for formation of stable amorphous dispersions as a pragmatic method for polymer selection. Reduced crystallization temperature of API, a parameter introduced by Zhou et al.,1 was utilized in this study for rank ordering interactions in API-polymeric systems. The trends in reduced crystallization temperature monitored over polymer concentration range of up to 20% polymer loading were utilized to calculate "crystallization parameter" or CP for two model systems (nifedipine and BI ABC). The rank order of CP, i.e., a measure of API-polymer interaction, for nifedipine followed the order PVP > PVP-VA > Soluplus > HPMCAS > PV Ac > PAA. This rank ordering was correlated to published results of molecular interactions and physical stability for nifedipine. A different rank ordering was observed for BI ABC: PAA > PVP > HPMCAS > Soluplus > PVPV-VA > PVAc. Interactions for BI ABC were not as differentiated when compared to nifedipine based on CP trends. BI ABC dispersions at drug loadings between 40 and 60% were physically stable for prolonged periods under ICH conditions as well as accelerated stress. We propose that large CP differences among polymers could be predictive of stability outcomes. Acceptable stability at pharmaceutically relevant drug loadings would suggest that the relative influence of downstream processes, such as polymer solubility in various solvents, process suitability and selection, and more importantly supersaturation potential, should be higher compared to stability considerations while developing compounds like BI ABC. PMID- 27414756 TI - 5-hydroxymethylcytosine marks postmitotic neural cells in the adult and developing vertebrate central nervous system. AB - The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. J. Comp. Neurol. 525:478-497, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27414757 TI - Catalytic Proton Dynamics at the Water/Solid Interface of Ceria-Supported Pt Clusters. AB - Wet conditions in heterogeneous catalysis can substantially improve the rate of surface reactions by assisting the diffusion of reaction intermediates between surface reaction sites. The atomistic mechanisms underpinning this accelerated mass transfer are, however, concealed by the complexity of the dynamic water/solid interface. Here we employ ab initio molecular dynamics simulations to disclose the fast diffusion of protons and hydroxide species along the interface between water and ceria, a catalytically important, highly reducible oxide. Up to 20% of the interfacial water molecules are shown to dissociate at room temperature via proton transfer to surface O atoms, leading to partial surface hydroxylation and to a local increase of hydroxide species in the surface solvation layer. A water-mediated Grotthus-like mechanism is shown to activate the fast and long-range proton diffusion at the water/oxide interface. We demonstrate the catalytic importance of this dynamic process for water dissociation at ceria-supported Pt nanoparticles, where the solvent accelerates the spillover of ad-species between oxide and metal sites. PMID- 27414758 TI - Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment. AB - NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the druggability of new protein targets. Protein-observed (19)F-NMR (PrOF NMR) using (19)F-labeled amino acids generates relatively simple spectra that are able to provide dynamic structural information toward understanding protein folding and function. Changes in these spectra upon the addition of fragment molecules can be observed and quantified. This protocol describes the sequence-selective labeling of three proteins (the first bromodomains of Brd4 and BrdT, and the KIX domain of the CREB-binding protein) using commercially available fluorinated aromatic amino acids and fluorinated precursors as example applications of the method developed by our research group. Fragment-screening approaches are discussed, as well as Kd determination, ligand efficiency calculations and druggability assessment, i.e., the ability to target these proteins using small-molecule ligands. Experiment times on the order of a few minutes and the simplicity of the NMR spectra obtained make this approach well-suited to the investigation of small- to medium-sized proteins, as well as the screening of multiple proteins in the same experiment. PMID- 27414761 TI - Effects of off-resonance spins on the performance of the modulated gradient spin echo sequence. AB - Translational molecular dynamics in various materials can also be studied by diffusion spectra. These can be measured by a constant gradient variant of the modulated gradient spin echo (MGSE) sequence which is composed of a CPMG RF pulse train superimposed to a constant magnetic field gradient. The application of the RF train makes the effective gradient oscillating thus enabling measurements of diffusion spectra in a wide range of frequencies. However, seemingly straightforward implementation of the MGSE sequence proved to be complicated and can give overestimated results for diffusion if not interpreted correctly. In this study, unrestricted diffusion in water and other characteristic materials was analyzed by the MGSE sequence in the frequency range 50-3000Hz using a 6T/m diffusion probe. First, it was shown that the MGSE echo train acquired from the entire sample decays faster than the train acquired only from a narrow band at zero frequency of the sample. Then, it was shown that the decay rate is dependent on the band's off-resonance characterized by the ratio Deltaomega0/omega1 and that with higher off-resonances the decay is faster. The faster decay therefore corresponds to a higher diffusion coefficient if the diffusion is calculated using standard Stejskal-Tanner formula. The result can be explained by complex coherence pathways contributing to the MGSE echo signals when |Deltaomega0|/omega1>0. In a magnetic field gradient, all the pathways are more diffusion attenuated than the direct coherence pathway and therefore decay faster, which leads to an overestimation of the diffusion coefficient. A solution to this problem was found in an efficient off-resonance signal reduction by using only zero frequency filtered MGSE echo train signals. PMID- 27414759 TI - High-mass-resolution MALDI mass spectrometry imaging of metabolites from formalin fixed paraffin-embedded tissue. AB - Formalin-fixed and paraffin-embedded (FFPE) tissue specimens are the gold standard for histological examination, and they provide valuable molecular information in tissue-based research. Metabolite assessment from archived tissue samples has not been extensively conducted because of a lack of appropriate protocols and concerns about changes in metabolite content or chemical state due to tissue processing. We present a protocol for the in situ analysis of metabolite content from FFPE samples using a high-mass-resolution matrix-assisted laser desorption/ionization fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR-MSI) platform. The method involves FFPE tissue sections that undergo deparaffinization and matrix coating by 9-aminoacridine before MALDI-MSI. Using this platform, we previously detected ~1,500 m/z species in the mass range m/z 50-1,000 in FFPE samples; the overlap compared with fresh frozen samples is 72% of m/z species, indicating that metabolites are largely conserved in FFPE tissue samples. This protocol can be reproducibly performed on FFPE tissues, including small samples such as tissue microarrays and biopsies. The procedure can be completed in a day, depending on the size of the sample measured and raster size used. Advantages of this approach include easy sample handling, reproducibility, high throughput and the ability to demonstrate molecular spatial distributions in situ. The data acquired with this protocol can be used in research and clinical practice. PMID- 27414760 TI - A real-time fluorometric method for the simultaneous detection of cell death type and rate. AB - Several cell death assays have been developed based on a single biochemical parameter such as caspase activation or plasma membrane permeabilization. Our fluorescent apoptosis/necrosis (FAN) assay directly measures cell death and distinguishes between caspase-dependent apoptosis and caspase-independent necrosis of cells grown in any multiwell plate. Cell death is monitored in standard growth medium as an increase in fluorescence intensity of a cell impermeable dye (SYTOX Green) after plasma membrane disintegration, whereas apoptosis is detected through caspase-mediated release of a fluorophore from its quencher (DEVD-amc). The assay determines the normalized percentage of dead cells and caspase activation per condition as an end-point measurement or in real time (automated). The protocol can be applied to screen drugs, proteins or siRNAs for interference with cell death while simultaneously detecting cell death modality switching between apoptosis and necrosis. Initial preparation may take up to 5 d, but the typical hands-on time is ~2 h. PMID- 27414762 TI - A Bayesian approach to quantifying uncertainty from experimental noise in DEER spectroscopy. AB - Double Electron-Electron Resonance (DEER) spectroscopy is a solid-state pulse Electron Paramagnetic Resonance (EPR) experiment that measures distances between unpaired electrons, most commonly between protein-bound spin labels separated by 1.5-8nm. From the experimental data, a distance distribution P(r) is extracted using Tikhonov regularization. The disadvantage of this method is that it does not directly provide error bars for the resulting P(r), rendering correct interpretation difficult. Here we introduce a Bayesian statistical approach that quantifies uncertainty in P(r) arising from noise and numerical regularization. This method provides credible intervals (error bars) of P(r) at each r. This allows practitioners to answer whether or not small features are significant, whether or not apparent shoulders are significant, and whether or not two distance distributions are significantly different from each other. In addition, the method quantifies uncertainty in the regularization parameter. PMID- 27414763 TI - Do we need antiplatelet therapy in thrombocytosis? Contra. Proposal for an individualized risk-adapted treatment. AB - Thrombocytosis is a frequent laboratory finding but not a diagnosis. Therefore, elevated platelet counts (>450 x 109/l) require careful diagnostic work-up to differentiate between reactive thrombocytosis (RT), caused by various conditions, and essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN). In either setting, aspirin is widely used in clinical practice. However, RT (even at platelet counts >1000 x 109/l) has never been shown to cause thrombosis or bleeding due to acquired von Willebrand factor defects in association with high platelet counts. Identification of reactive conditions and appropriate therapy of the underlying disorder are most relevant. By contrast to RT, ET and related MPN can be associated with thrombosis and/or hemorrhage. Current recommendations suggest the use of low-dose aspirin in all patients with ET unless contraindicated. However, the strength of this recommendation is weak, i. e. evidence level IIb grade B. A potential benefit of aspirin used for primary thromboprophylaxis in ET is mostly derived from the ECLAP study in polycythemia vera (PV). However, translating study results from PV to ET appears to be highly questionable and may be biased. In the absence of robust data regarding the benefit-risk balance of aspirin in ET, it appears reasonable (1) to stratify patients according to their individual thrombotic and bleeding risk, (2) to restrict the use of aspirin to high-risk categories and patients with microcirculatory disturbances, (3) to test for pharmacological efficacy (COX-1 inhibition; measurement of TXB2), and (4) to modify the aspirin dosing regimen (twice instead of once daily) if required. PMID- 27414764 TI - Aromatic Substituent Effects on the Flexibility of Metal-Organic Frameworks. AB - The flexibility (or breathing behavior) of zinc-based metal-organic frameworks (MOFs) has been manipulated by regioisomeric and positional control of organic functionalities. Ten new regioisomeric BDC (ortho- or para-disubstituted benzene 1,4-dicarboxylic acid) ligands have been synthesized and applied to a DMOF (dabco MOF) system, which has a zinc(II) paddle-wheel SBU (secondary building unit). Among the new regioisomeric MOFs, the NH2-OMe combination showed significant flexibility (breathing behavior) changes by simply altering the functional group positions (from 2,3 to 2,5). The electronic density of the benzene ring was considered to be a major factor in the flexibility changes in the regioisomeric MOF system. PMID- 27414765 TI - How contrary can you get? PMID- 27414766 TI - Myeloperoxidase: a key regulator of neutrophil oxidant production. AB - Myeloperoxidase plays a fundamental role in oxidant production by neutrophils. This heme enzyme uses hydrogen peroxide and chloride to catalyze the production of hypochlorous acid, which is the major strong oxidant generated by neutrophils in appreciable amounts. In addition to chlorination, myeloperoxidase displays several other activities. It readily oxidizes thiocyanate to hypothiocyanite, converts a myriad of organic substrates to reactive free radicals, and hydroxylates aromatic compounds. Depending on the concentration of its competing substrates and the conditions of the local environment, myeloperoxidase could substantially affect oxidant production by neutrophils. Superoxide is undoubtedly a physiological substrate for myeloperoxidase. Its interactions with the enzyme are key factors in determining how neutrophils use superoxide to kill pathogens and promote inflammatory tissue damage. Superoxide modulates the chlorination and peroxidation activities of myeloperoxidase. It also reacts with the enzyme to form oxymyeloperoxidase which is catalytically active and hydroxylates phenolic substrates. Myeloperoxidase reacts rapidly with nitric oxide and peroxynitrite so that at sites of inflammation there is a strong possibility that these reactions will impact on oxidative damage caused by neutrophils. Under certain conditions, many substrates of myeloperoxidase act as inhibitors and regulate oxidant production by the enzyme. Given the numerous reactions of myeloperoxidase, all its activities should be considered when assessing the injurious oxidants produced by neutrophils. PMID- 27414767 TI - Comparison of salicylate and D-phenylalanine for detection of hydroxyl radicals in chemical and biological reactions. AB - Hydroxylation of salicylate and D-phenylalanine was measured to test the usefulness of these compounds for hydroxyl radical (HO(*)) detection in chemical and biological systems. When HO(*) were produced by the photolytic decomposition of hydrogen peroxide, nearly equal amounts of 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were produced from salicylate, with catechol as a minor product. In the photolytic reaction, nearly equal concentrations of p-,m-, and o-tyrosine were formed from D-phenylalanine. When salicylate or D-phenylalanine was present with Fenton reagents or in iron(II) autoxidation systems, the relative proportions of hydroxylated products were similar to those observed after photolysis, although less total products were usually detected. In contrast, when similar experiments were conducted with isolated hepatic microsomes and perfused livers, 2,5-DHBA was the primary product from salicylate, and p-tyrosine was the major product from D phenylalanine. Cytochrome P-450 enzymes can hydroxylate salicylate to produce 2,5 DHBA, and it is likely that phenylalanine hydroxylase produces most of the p tyrosine detected in hepatic tissues. Thus, although both salicylate and D phenylalanine are useful probes for hydroxyl radical formation in chemical systems, hydroxylated products formed from enzymatic reactions complicate interpretation of data from both compounds in vivo. PMID- 27414768 TI - Carbon tetrachloride-induced free radical mediated protein oxidation in vitro and in vivo. AB - Trichloromethyl and trichloromethylperoxyl free radicals generated by UVC light activation of carbon tetrachloride promote the formation of protein carbonyls in chicken egg albumin in vitro. Further, UVC light itself exerts a highly significant equivalent effect of its own. The reaction was significantly blocked by Trolox but not by alpha-tocopherol at a concentration of 1 mM. EDTA (3 mM) partially prevented the oxidative effects of (*)CCl3 or CCl3O2(*) in proteins but not those of UV light. Rat liver microsomes in the presence of NADPH also led to the formation of carbonyl groups in microsomal proteins. That effect was significantly enhanced by the presence of CCl4 in the incubation mixture. Liver microsomes from CCl4 poisoned animals exhibited significantly increased levels of protein carbonyls at 1 and 2 h after administration but not at 3 h. These results suggest that proteins might be targets of CCl4 oxidative effects. Protein carbonyls might arise from either direct attack by (*)CCl3 or CCl3O2(*), or from 4-hydroxynonenal reaction via Michael addition with amino acids at the aldehyde double bond and retaining the carbonyl group attached to the target protein. PMID- 27414769 TI - Redox stress and hepatic DNA fragmentation induced by diquat in vivo are not accompanied by increased 8-hydroxydeoxyguanosine contents. AB - Administration of 0.1 mmol/kg of diquat to Fischer-344 rats causes acute hepatic necrosis by mechanisms that appear to involve increased generation of reactive oxygen species, but the critical targets of the proposed oxidations have not been identified. In the present study the effects of diquat-induced redox stresses on hepatic protein thiol status were determined by derivatization of subcellular fractions with monobromobimane and separation of the fluorescent derivatives by SDS-PAGE. No differences in hepatic thiol status were seen in animals 2 or 6 h after diquat, relative to saline-treated controls, despite documentation of injury by elevated plasma transaminase activities. Hepatic DNA fragmentation was increased in diquat-treated animals (24.9+/-5.1 vs 6.7+/-0.3% (controls) at 2 h; 57.2+/-4.1 vs 4.6+/-0.3% (controls) at 6 h, P<0.001). However, 8 hydroxydeoxyguanosine (8-OHdG) contents in hepatic DNA were not increased by diquat (35.3+/-6.2 MUmol 8-OHdG/mol deoxyguanosine (dG)) over saline-treated controls (28.3+/-2.6). Plasma NH3 concentrations increased in diquat-treated rats from 49 MUM in controls to 170 MUM 6 h after treatment with diquat. Hepatic activities of glutamine synthetase (GS) were lower in diquat-treated rats (39.7+/ 13.0 mU/mg protein) than in controls (65.8+/-13.4, P<0.001), but activities of carbamyl phosphate synthetase-I (CPS-I), were not decreased significantly. The oxidation of proteins to forms reactive with 2,4-dinitrophenylhydrazine (DNPH) was investigated in subcellular fractions by Western blot analyses with a monoclonal antibody to DNP-derivatized bovine serum albumin (BSA). N-terminal sequencing of bands exhibiting reactivity with anti-DNP-BSA antibodies indicated protein carbonyl formation in malate dehydrogenase, protein disulfide isomerase, and glutathione transferase. The functional consequences of oxidation of these proteins are not known but the observation of protein carbonyl formation and no measurable loss of protein thiol content are consistent with iron chelate mediated oxidation in the transformation critical to expression of tissue damage. The time course data are consistent with DNA fragmentation as a mechanism contributing to the development of cell injury, but the absence of increases in 8 OHdG indicates that direct oxidation of DNA may not be responsible. PMID- 27414770 TI - Reactions of non-steroidal anti-inflammatory drugs with polyacrylamide free radicals. AB - The free radical reactivity of a number of currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) (sulindac, diflunisal, piroxicam, naproxen, ibuprofen, indomethacin and aspirin) was studied by observing their action on the free radical polymerization of acrylamide initiated by the thermal decomposition of potassium peroxodisulfate in aqueous solution at pH 7 and 50 degrees C. Analysis of the kinetics of the polymerization reaction showed that sulindac, diflunisal, piroxicam, indomethacin and aspirin reacted directly with the carbon centred polyacrylamide free radicals, thereby retarding the polymerization. The specific rate constants for reaction of sulindac, diflunisal, piroxicam, indomethacin and aspirin with polyacrylamide radicals at pH 7, ionic strength 0.1 M and 50 degrees C were found to be 6850, 262, 76, 30 and 21 M(-1) s(-1) respectively. The reaction mechanism is postulated to involve reduction of the drug. On the other hand, naproxen and ibuprofen were able to react with the initiating SO4(*-) radicals, causing inhibition of the polymerization and oxidation of the drug. This study verifies the ability of NSAIDs to react as free radical scavengers and potentially to participate as a chain breaking agent in 'oxidative stress' in biological systems. Among them, sulindac is the most selective and effective when interacting with the carbon-centred radicals, and this may be a reflection of the rapid reduction in vivo of sulindac to its active sulphide metabolite. PMID- 27414771 TI - Photoinactivation of cellular catalase by ultraviolet radiation. AB - Photoinactivation of catalase is found to be similar in solution and in human normal skin fibroblasts exposed to ultraviolet B, ultraviolet A and near visible light, and the kinetics of such photoinactivation obey first order processes. The action spectrum, measured for the first time in cells, suggests that catalase photoinactivation in solution and in cells proceeds via similar routes. In both systems, no protective effect was observed with diethyldithiocarbamate, a superoxide dismutase inhibitor, with desferrioxamine, an iron chelator which impedes the production of hydroxyl radical via the Fenton reaction, and with vitamin E which scavenges peroxyl radical to protect against membrane peroxidative process. While the absence of protection by these inhibitors may be anticipated for the photoinactivation of catalase in solution, the lack of effect in cells suggests that reactive oxygen species produced by endogenous photosensitization are not responsible for the enzyme inactivation. Moreover, the already established protective effect of ethanol in solution is also observed in cells, supporting the view that photoinactivation in solution and in cells is due to the same primary events. PMID- 27414772 TI - Oxidative stress does not mediate heat shock-induced cell damage and apoptosis. AB - The hypothesis that oxidative damage arising from heat shock might significantly contribute to cell death and in particular to apoptosis has been tested in human peripheral blood lymphocytes. Cellular glutathione content and protein carbonyl groups were measured as indicators of oxidative injury. Cell viability and proliferative capacity were evaluated as measures of irreversible damage. Heat shock caused dose-dependent decreases in cell viability, and apoptotic cell death was found to be a major component of heat-shock-mediated mortality. However, only the more severe heat treatment (1 h, 45 degrees C) caused an immediate decrease in glutathione content. The content in carbonyl groups was not significantly affected by heat shock. N-acetyl-cysteine, when added before the hyperthermic treatment, did increase the glutathione content of the cells, but this did not favourably affect the survival of heat-shocked lymphocytes. It is suggested that oxidative damage is not a significant component of heat shock-mediated cell injury, and that, at least in this experimental model, apoptosis is triggered by stimuli other than an altered redox state of the cell. PMID- 27414773 TI - Oxidant-induced apoptosis: a consequence of lethal lysosomal leak? AB - When macrophage-like J-774 cells are subjected to limited oxidative stress, such as exposure to hydrogen peroxide in a moderate bolus dose, some of their lysosomes rupture-as here assayed by the acridine orange relocalization test secondary to intralysosomal, iron-catalysed, oxidative reactions. The resultant leakage into the cytosol of hydrolytic enzymes, such as cathepsin-D (as shown here), may initiate a slow degradation/fragmentation process of an apoptotic type within cells still having intact plasma membranes. In contrast, severe oxidative stress also results in extensive lysosomal rupture but leads to necrosis. The chelation of (normally occurring) intralysosomal low-molecular weight iron, by endocytotic uptake of desferrioxamine, largely prevents oxidative stress-induced apoptosis whereas lysosomal iron-loading, by endocytotic uptake of complexed ferric iron, considerably enhances the process. We conclude that oxidant-mediated and iron-catalysed lysosomal rupture leads to decompartmentalization of lysosomal enzymes which in turn may initiate and promote the apoptotic process. PMID- 27414774 TI - Free radicals and memory loss. PMID- 27414776 TI - Stable and Flexible CuInS2/ZnS:Al-TiO2 Film for Solar-Light-Driven Photodegradation of Soil Fumigant. AB - Semiconductor quantum dots (QDs) are suitable light absorbers for photocatalysis because of their unique properties. However, QDs generally suffer from poor photochemical stability against air, limiting their applications in photocatalysis. In this study, a stable solar-light-driven QDs-containing photocatalytic film was developed to facilitate photocatalytic degradation of the soil fumigant 1,3-dichloropropene (1,3-D). Highly stable CuInS2/ZnS:Al core/shell QDs (CIS/ZnS:Al QDs) were synthesized by doping Al into the ZnS shell and controlling ZnS:Al shell thickness; the CIS/ZnS:Al QDs were subsequently combined with TiO2 to form a CIS/ZnS:Al-TiO2 photocatalyst. The optimized ZnS:Al shell thickness for 1,3-D photodegradation was approximately 1.3 nm, which guaranteed and balanced the good photocatalytic activity and stability of the CIS/ZnS:Al TiO2 photocatalyst. The photodegradation efficiency of 1,3-D can be maintained up to more than 80% after five cycles during recycling experiment. When CIS/ZnS:Al TiO2 was deposited as photocatalytic film on a flexible polyethylene terephthalate substrate, over 99% of cis-1,3-D and 98% of trans-1,3-D were depleted as they passed through the film during 15 h of irradiation under natural solar light. This study demonstrated that the stable CIS/ZnS:Al-TiO2 photocatalyst both in powder and film form is a promising agent for photodegradation and emission reduction of soil fumigants. PMID- 27414775 TI - Race and Sex Differences in Adult Facial Fracture Risk. AB - Importance: There are well-described racial, sex, and age differences related to osteoporosis and hip and/or extremity fractures. Nonetheless, there has been virtually no inquiry evaluating whether these findings carry over to facial fracture. Objective: To characterize the incidence of facial fractures by patient demographics and injury mechanism, focusing on whether differences are noted with race, sex, and advancing age. Main Outcomes and Measures: Retrospective analysis of the National Electronic Injury Surveillance System (NEISS) was performed in October and November 2015, specifically evaluating adult emergency department (ED) visits from 2012 to 2014 related to facial trauma. Entries were organized by age groups (both individual decades as well as younger adults [18-59 years] vs older adults [60-89 years]), sex, and race (white, black, Asian, other/unspecified). Incidence of facial fractures and mechanism of injury were also evaluated. Results: There were 33 825 NEISS entries correlating to 1 401 196 ED (range, 1 136 048-1 666 344) visits for adult facial injury, with 14.4% involving fracture. A greater proportion of facial injuries among younger men (<60 years) were fractures relative to younger women (15.5% vs 12.5%; difference of the mean [DOM], 3.0%; 95% CI, 2.8%-3.1%; P < .001); however, on comparison by sex in elderly populations (>= 60 years), women had an increased fracture predilection (15.0% vs 14.0%; DOM, 1.0%; 95% CI, 0.8%-1.2%; P < .001). Also, older women had a significantly greater risk of fracture relative to those younger than 60 years (15.0% vs 12.5%; DOM, 2.5%; 95% CI, 2.4%-2.7%; P < .001), a comparison that was significant among whites and Asians. Black women had a significantly decreased risk of fracture in the older aged population. (8.4% vs 9.1%; DOM, 0.7%; 95% CI, 0.2%- 1.3%; P = .001). Both on individual comparisons of younger and older cohorts, white and Asian individuals of either sex had significantly greater rates of facial fracture injury than blacks. Among younger cohorts in either sex, injuries sustained during participation in recreational activities were a significant factor, replaced largely by injuries due to housing structural elements and falls among older cohorts. Conclusions and Relevance: There is an increase in the risk of facial fracture among postmenopausal women sustaining facial injuries, with these results significant among whites and Asians. In contrast, a decreased risk was noted on comparison of younger and older black women. Mechanism of injuries also varied significantly by age, race, and sex. Level of Evidence: 4. PMID- 27414777 TI - [The role of microRNA in abiotic stress response in plants]. AB - Regulation of gene expression via microRNA is the key mechanism of response to biotic and abiotic stresses in plants. There are a lot of experimental data on the biological function of microRNAs in response to different stresses in various plant species. This review contains up-to-date information on molecular mechanisms of microRNA action in plants in response to abiotic stresses, including drought, salinity, mineral nutrient deficiency or imbalance. PMID- 27414778 TI - [Key molecular mechanisms associated with cell malignant transformation in acute myeloid leukemia]. AB - Cancer, along with cardiovascular disorders, is one of the most important problems of healthcare. Pathologies of the hematopoietic system are the most prevalent in patients under 30 years of age, including acute myeloid leukemia (AML), which is widespread and difficult to treat. The review considers the mechanisms that play a significant role in AML cell malignant transformation and shows the contributions of certain genes to both remission and resistance of AML cells to various treatments. PMID- 27414779 TI - [VLP vaccines and effects of HIV-1 Env protein modifications on their antigenic properties]. AB - An ideal protective HIV-1 vaccine can elicit broadly neutralizing antibodies, capable of preventing HIV transmission. The strategies of designing vaccines include generation of soluble recombinant proteins which mimic the native Env complex and are able to enhance the immunogenicity of gp120. Recent data indicate that the cytoplasmic tail (CT) of the Env protein has multiple functions, which can affect the early steps of infection, as well as viral assembly and antigenic properties. Modifications in the CT can be used to induce conformational changes in functional regions of gp120 and to stabilize the trimeric structure, avoiding immune misdirection and induction of non-neutralizing antibody responses. Env trimers with modified CTs in virus-like particles (VLPs) are able to induce antibodies with broad spectrum neutralizing activity and high avidity and have the potential for developing an effective vaccine against HIV. PMID- 27414780 TI - [Nutrient restriction in combinatory therapy of tumors]. AB - The main objective of anticancer treatment is the elimination of degenerated cells by the induction of programmed cell death. Various chemotherapy drugs and radiation are able to activate cell death mechanisms in tumors. However, unfortunately, monotherapy will always be insufficiently effective because of the variety and virulence of tumors, as well as their ability to develop resistance to drugs. Moreover, monotherapy might constrain many negative side effects. Therefore, the combination of different approaches and/or drugs will increase the efficiency of treatment. One such promising approach is the combination of nutrient restriction (NR) and various chemotherapeutic drugs. This approach may not only affect the autophagy but also influence apoptotic cell death. This review is focused on the potential of NR use in anticancer therapy, as well as the molecular mechanisms underlying this approach. PMID- 27414781 TI - [Functional analysis of Grp and Iris, the gag and env domesticated errantivirus genes, in the Drosophila melanogaster genome]. AB - Drosophila melanogaster is the only invertebrate that contains endogenous retroviruses, which are called errantiviruses. Two domesticated genes, Grp and Iris, which originate from errantivirus gag and env, respectively, have been found in the D. melanogaster genome. The functions performed by the genes in Drosophila are still unclear. To identify the functions of domesticated gag and env in the D. melanogaster genome, expression of Iris and Grp was studied in strains differing by the presence or absence of the functional gypsy errantivirus. In addition, the expression levels were measured after injection of gram-positive and gram-negative bacteria, which activate different immune response pathways, and exposure to various abiotic stress factors. The presence of functional D. melanogaster retrovirus gypsy was found to increase the Grp expression level in somatic tissues of the carcass, while exerting no effect on the Iris expression level. Activation of the immune response in D. melanogaster by bacteria Bacillus cereus increased the Grp expression level and did not affect Iris expression. As for the effects of abiotic stress factors (oxidative stress, starvation, and heat and cold stress), the Grp expression level increased in response to starvation in D. melanogaster females, and the Iris expression level was downregulated in heat shock and oxidative stress. Based on the findings, Grp was assumed to play a direct role in the immune response in D. melanogaster; Iris is not involved in immune responses, but and apparently performs a cell function that is inhibited in stress. PMID- 27414782 TI - [Panel of X-linked single-nucleotide polymorphic markers for DNA identification (XSNPid) based on multiplex genotyping by multilocus PCR and MALDI-TOF mass spectrometry]. AB - Human genetic markers linked with the X chromosome (X-linked) are used in the field of population and medical genetics, as well as for DNA identification of individuals in forensic science and forensic medicine. We proposed an XSNPid panel that consists of 66 unlinked single nucleotide X chromosome markers and developed a protocol for their multiplex genotyping using multilocus PCR and MALDI-TOF mass spectrometry. The XSNPid panel is genotyped within two multiplexes (36 and 30 markers). The developed protocol provides an efficient genotype reading; the fraction of determined genotypes is 98.29%. The high level of gene diversity (0.461) for the X-linked SNPs included in the panel is characteristic of the Russian population. A total of 63 out of 66 markers that provide a high efficiency of genotyping and independent inheritance are suitable for DNA identification purposes. The XSNPid panel is characterized by a very high discriminating ability when studying the Russian population. The probability of genotype coincidence in two unrelated individuals is 9 * 10^(-27) for women and 2 * 10^(-18) for men. Also, the XSNPid panel has a greater multiplex capacity in addition to a higher discriminating ability compared to the other closest analogues of the X chromosome SNP sets, which makes it more cost effective and less time consuming. The XSNPid panel is a convenient tool, not only for individual DNA identification, but also for population genetic studies. PMID- 27414783 TI - [SPINK3: A novel growth factor that promotes rat liver regeneration]. AB - Serine peptidase inhibitor, Kazal type 3 (SPINK3) is a trypsin inhibitor, and also a growth factor that has an identical structure to epidermal growth factor (EGF), which could combine with epidermal growth factor receptor (EGFR) to promote cell proliferation. To shed light on the role and regulation mechanism of SPINK3 in rat liver regeneration (LR), Rat Genome 230 2.0 assay was used to detect the expression profiles of LR genes after partial hepatectomy (PH). The results showed that Spink3 was significantly up-regulated at 2-24 h and 72-168 h after PH. In the present study, RT-PCR and immunoblotting were used to validate the assay results. Ingenuity Pathway Analysis 9.0 (IPA) software was used to build the SPINK3 signaling regulating LR and analyze the possible mechanism. And then the expression of cell proliferation-associated gene Ccna2 was examined by RT-PCR in normal rat liver cell line BRL-3A in which Spink3 was overexpressed. The results showed that Ccna2 was significantly up-regulated in BRL-3A in which Spink3 was over-expressed. SPINK3 combining with EGFR accelerated cell proliferation during rat liver regeneration via P38, PKC, JAK-STAT and AKT pathways. Thus, SPINK3 was likely to promote hepatocytes proliferation in LR through P38, PKC, JAK-STAT and AKT. PMID- 27414784 TI - [Production of recombinant human interleukin-38 and its inhibitory effect on the expression of proinflammatory cytokines in THP-1 cells]. AB - Interleukin (IL)-38 is the latest member of the IL-1 cytokine family. However, as a result of lacking efficient method to generate relatively large quantity of IL 38, its precise functions are poorly understood. In the present study, the cloning, expression, purification, and activity analysis of recombinant human IL 38 was described. Human IL-38 cDNA was cloned into the prokaryotic expression vector pET-44. The recombinant IL-38 containing a C-hexahistidine tag was expressed in Escherichia coli BL21 (DE3) which induced by isopropyl-beta-D thiogalactoside. The expressed fusion protein was purified by Ni-NTA affinity chromatography. IL-38 protein was largely found in the soluble fraction. The purified IL-38 appeared a single band on SDS-PAGE, the yield of IL-38 was 4 mg from 1 L of bacterial culture, and the purity was more than 98% with low endotoxin level (<0.1 EU/MUg). Western blotting confirmed the identity of the purified protein. Activity analysis showed that IL-38 can inhibit effectively the expression of proinflammatory cytokines, such as tumor necrosis factor-alpha, IL 1beta, IL-17, and monocyte chemoattractant protein-1 in lipopolysaccharide activated THP-1 cells. The production and characterization of biologically active IL-38 will be beneficial for its potential role in clinical applications. PMID- 27414785 TI - [Detection of BCR-ABL gene mutations in chronic myeloid leukemia using biochips]. AB - A biochip-based method was developed to identify the BCR-ABL mutations that affect the thyrosine kinase domain and determine resistance to targeted therapy with thyrosine kinase inhibitors. The method is based on RT-PCR followed by allele-specific hybridization on a biochip with immobilized oligonucleotide probes. The biochip addresses 11 mutations, which are responsible for up to 85% of imatinib resistance cases. A method to decect the clinically significant mutation T315I was designed on the basis of LNA-clamped PCR and proved highly sensitive, detecting the mutation in clinical samples with a leukemic cell content of 5% or higher. The method was validated using clinical samples from chronic myeloid leukemia (CML) patients with acquired resistance to imatinib. The results of hybridization on biochip were verified by Sanger sequencing. PMID- 27414786 TI - [Mutation frequencies in HIV-1 subtype-A genome in regions containing efficient RNAi targets]. AB - The development of gene-therapy technology using RNAi for AIDS/HIV-1 treatment is a prospective alternative to traditional anti-retroviral therapy. RNAi targets could be selected in HIV-1 transcripts and in CCR5 mRNA. Previously, we experimentally selected a number of efficient siRNAs that target HIV-1 RNAs. The viral genome mutates frequently, and RNAi strength is very sensitive, even for a single mismatches. That is why it is important to study nucleotide sequences of targets in clinical isolates of HIV-1. In the present study, we analyzed mutations in 6 of about 300-bp regions containing RNAi targets from HIV-1 subtype A isolates in Russia. Estimates of the mean frequencies of mutations in the targets were obtained and the frequencies of mutations in the different codon positions were compared. The frequencies of mutations in the vicinity of the targets and directly within the targets were also compared and have been shown to be approximately the same. The frequencies of indels in the chosen regions have been assessed. Their frequencies have proved to be two to three orders of magnitude less compared to that for mutations. PMID- 27414787 TI - [Effect of Hepatitis C virus proteins on the production of proinflammatory and profibrotic cytokines in Huh7.5 human hepatoma cells]. AB - Hepatitis C virus (HCV) is a widespread dangerous human pathogen. Up to 80% of HCV-infected individuals develop chronic infection, which is often accompanied by liver inflammation and fibrosis and, at terminal stages, liver cirrhosis and cancer. Treatment of patients with end-stage liver disease is often ineffective, and even patients with suppressed HCV replication have higher risk of death as compared with noninfected subjects. Therefore, investigating the mechanisms that underlie HCV pathogenesis and developing treatments for virus-associated liver dysfunction remain an important goal. The effect of individual HCV proteins on the production of proinflammatory and profibrotic cytokines in hepatocellular carcinoma Huh7.5 cells was analyzed in a systematic manner. Cells were transfected with plasmids encoding HCV proteins. Cytokine production and secretion was accessed by immunocytochemistry and ELISA of the culture medium, and transcription of the cytokine genes was assessed using reverse transcription and PCR. HCV proteins proved to differ in effect on cytokine production. Downregulation of interleukin 6 (IL-6) production was observed in cells expressing the HCV core, NS3, and NS5A proteins. Production of transforming growth factor beta1 (TGF-beta1) was lower in cells expressing the core proteins, NS3, or E1/E2 glycoproteins. A pronounced increase in production and secretion of tumor necrosis factor alpha (TNF-alpha) was observed in response to expression of the HCV E1/E2 glycoproteins. A higher biosynthesis, but a lower level in the cell culture medium, was detected for interleukin 1beta (IL-1beta) in cells harboring NS4 and IL-6 in cells expressing NS5V. The finding was possibly explained by protein-specific retention and consequent accumulation of the respective cytokines in the cell. PMID- 27414788 TI - [ZNF143 is involved in CTCF-mediated chromatin interactions by cooperation with cohesin and other partners]. AB - ZNF143 is a ubiquitously expressed transcription factor conserved in vertebrates and might regulate the expression of numerous genes. But its function in mediating chromatin interactions remains elusive. By integrated analysis of public datasets, we provided evidence that a majority of ZNF143 binding sites (BSs) were involved in CTCF-mediated chromatin interaction networks (CTCF-CINs) by overlapping with cohesin-BSs and CTCF-BSs. We further showed that only a very few CTCF-CINs were associated with ZNF143 alone, whereas those associated with ZNF143 and cohesin simultaneously were highly overlapped with constitutive, conserved CTCF-BSs and enriched at boundaries of chromatin topologically associating domains. These observations implicate that as an important partner of CTCF, ZNF143 helps it establish the conserved chromatin structure by cooperating with cohesin. PMID- 27414789 TI - [Interaction of two tumor suppressors: Phosphatase CTDSPL and Rb protein]. AB - Earlier we established that CTDSPL gene encoding small carboxy-terminal domain serine phosphatase can be considered a classical tumor suppressor gene. Besides, transfection of tumor cell line MCF-7 with CTDSPL led to the content decrease of inactive phosphorylated form of another tumor suppressor, retinoblastoma protein (Rb), and subsequently to cell cycle arrest at the G1/S boundary. This result implied that small phosphatase CTDSPL is able to specifically dephosphorylate and activate Rb protein. In order to add some fuel to this hypothesis, in the present work we studied the interaction of two tumor suppressors CTDSPL and Rb in vitro. GST pool-down assay revealed that CTDSPL is able to precipitate Rb protein from MCF-7 cell extracts, while surface plasmon resonance technique showed that interaction of the two proteins is direct. Results of this study reassert that phosphatase CTDSPL and Rb could be involved in the common mechanism of cell cycle regulation. PMID- 27414790 TI - [Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti DNA antibody fragment]. AB - Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage. PMID- 27414791 TI - [Calculation of mobility and entropy of the binding of molecules by crystals]. AB - A simple method for evaluating a range of molecular movements in crystals has been developed. This estimate is needed to calculate the entropy of binding, in particular in protein-ligand complexes. The estimate is based on experimental data concerning the enthalpy of sublimation and saturated vapor pressure obtained for 15 organic crystals with melting temperatures of 25-80 degrees S. For this set, we calculated the values of the average range and the corresponding average amplitude of molecular movements in crystals that constituted 0.75 +/- 0.14 A and 0.18 +/- 0.03 A, respectively. The entropy of sublimation calculated based on the average range of molecular movements in crystals was well consistent with the experimental data. PMID- 27414792 TI - [Detecting shared pathways linked to rheumatoid arthritis with other autoimmune diseases in a in silico analysis]. AB - Pathway-based analysis approach has exploded in use during the last several years. It is successful in recognizing additional biological insight of disease and finding groupings of risk genes that represent disease developing processes. Therefore, shared pathways, with pleiotropic effects, are important for understanding similar pathogenesis and indicating the common genetic origin of certain diseases. Here, we present a pathway analysis to reveal the potential disease associations between RA and three potential RA-related autoimmune diseases: psoriasis, diabetes mellitus, type 1 (T1D) and systemic lupus erythematosus (SLE). First, a comprehensive knowledge mining of public databases is performed to discover risk genes associated with RA, T1D, SLE and psoriasis; then by enrichment test of these genes, disease-related risk pathways are detected to recognize the pathways common for RA and three other diseases. Finally, the underlying disease associations are evaluated with the association rules mining method. In total, we identify multiple RA risk pathways with significant pleiotropic effects, the most unsurprising of which are the immunology related pathways. Meanwhile for the first time we highlight the involvement of the viral myocarditis pathway related to cardiovascular disease (CVD) in autoimmune diseases such as RA, psoriasis, T1D and SLE. Further Association rule mining results validate the strong association between RA and T1D and RA and SLE. It is clear that pleiotropy is a common property of pathways associated with disease traits. We provide novel pathway associations among RA and three autoimmune diseases. These results ascertain that there are shared genetic risk profiles that predispose individuals to autoimmune diseases. PMID- 27414794 TI - Dynamic Patterns of Expertise: The Case of Orthopedic Medical Diagnosis. AB - The aim of this study was to analyze dynamic patterns for scanning femoroacetabular impingement (FAI) radiographs in orthopedics, in order to better understand the nature of expertise in radiography. Seven orthopedics residents with at least two years of expertise and seven board-certified orthopedists participated in the study. The participants were asked to diagnose 15 anteroposterior (AP) pelvis radiographs of 15 surgical patients, diagnosed with FAI syndrome. Eye tracking data were recorded using the SMI desk-mounted tracker and were analyzed using advanced measures and methodologies, mainly recurrence quantification analysis. The expert orthopedists presented a less predictable pattern of scanning the radiographs although there was no difference between experts and non-experts in the deterministic nature of their scan path. In addition, the experts presented a higher percentage of correct areas of focus and more quickly made their first comparison between symmetric regions of the pelvis. We contribute to the understanding of experts' process of diagnosis by showing that experts are qualitatively different from residents in their scanning patterns. The dynamic pattern of scanning that characterizes the experts was found to have a more complex and less predictable signature, meaning that experts' scanning is simultaneously both structured (i.e. deterministic) and unpredictable. PMID- 27414793 TI - [Determination of proteomic and metabolic composition of exhaled breath condensate of newborns]. AB - Here, the possibility of proteomic and metabolomic analysis of the composition of exhaled breath condensate of neonates with respiratory support. The developed method allows non-invasive collecting sufficient amount of the material for identification of disease-specific biomarkers. Samples were collected by using a condensing device that was incorporated into the ventilation system. The collected condensate was analyzed by liquid chromatography coupled with high resolution mass spectrometry and tandem mass spectrometry. The isolated substances were identified with a use of databases for proteins and metabolites. As a result, a number of compounds that compose the exhaled breath condensate was determined and can be considered as possible biomarkers of newborn diseases or stage of development. PMID- 27414795 TI - A DNA Binding Protein Is Required for Viral Replication and Transcription in Bombyx mori Nucleopolyhedrovirus. AB - A DNA-binding protein (DBP) [GenBank accession number: M63416] of Bombyx mori nuclear polyhedrosis virus (BmNPV) has been reported to be a regulatory factor in BmNPV, but its detailed functions remain unknown. In order to study the regulatory mechanism of DBP on viral proliferation, genome replication, and gene transcription, a BmNPV dbp gene knockout virus dbp-ko-Bacmid was generated by the means of Red recombination system. In addition, dbp-repaired virus dbp-re-Bacmid was constructed by the means of the Bac to Bac system. Then, the Bacmids were transfected into BmN cells. The results of this viral titer experiment revealed that the TCID50 of the dbp-ko-Bacmid was 0; however, the dbp-re-Bacmid was similar to the wtBacmid (p>0.05), indicating that the dbp-deficient would lead to failure in the assembly of virus particles. In the next step, Real-Time PCR was used to analyze the transcriptional phases of dbp gene in BmN cells, which had been infected with BmNPV. The results of the latter experiment revealed that the transcript of dbp gene was first detected at 3 h post-infection. Furthermore, the replication level of virus genome and the transcriptional level of virus early, late, and very late genes in BmN cells, which had been transfected with 3 kinds of Bacmids, were analyzed by Real-Time PCR. The demonstrating that the replication level of genome was lower than that of wtBacmid and dbp-re-Bacmid (p<0.01). The transcriptional level of dbp-ko-Bacmid early gene lef-3, ie-1, dnapol, late gene vp39 and very late gene p10 were statistically significantly lower than dbp-re-Bacmid and wtBacmid (p<0.01). The results presented are based on Western blot analysis, which indicated that the lack of dbp gene would lead to low expressions of lef3, vp39, and p10. In conclusion, dbp was not only essential for early viral replication, but also a viral gene that has a significant impact on transcription and expression during all periods of baculovirus life cycle. PMID- 27414796 TI - Transcriptomic and Expression Analysis of the Salivary Glands in White-Backed Planthoppers, Sogatella furcifera. AB - The white-backed planthopper (WBPH), Sogatella furcifera (Horvath), is one of the serious rice pests because of its destructive feeding. The salivary glands of the WBPH play an important role in the feeding behaviour. Currently, however, very little is known about the salivary glands at the molecular level. We sequenced the salivary gland transcriptome (sialotranscripome) of adult WBPHs using the Illumina sequencing. A total of 65,595 transcripts and 51,842 unigenes were obtained from salivary glands. According to annotations against the Nr database, many of the unigenes identified were associated with the most studied enzymes in hemipteran saliva. In the present study, we identified 32 salivary protein genes from the WBPH sialotranscripome, which were categorized as those involved in sugar metabolism, detoxification, suppression of plant defense responses, immunity-related responses, general digestion, and other phytophagy processes. Tissue expression profiles analysis revealed that four of 32 salivary protein genes (multicopper oxidase 4, multicopper oxidase 6, carboxylesterase and uridine phosphorylase 1 isform X2) were primarily expressed in the salivary gland, suggesting that they played putative role in insect-rice interactions. 13 of 32 salivary protein genes were primarily expressed in gut, which might play putative role in digestive and detoxify mechanism. Development expression profiles analysis revealed that the expression level of 26 of 32 salivary protein genes had no significant difference, suggesting that they may play roles in every developmental stages of salivary gland of WBPH. The other six genes have a high expression level in the salivary gland of adult. 31 of 32 genes (except putative acetylcholinesterase 1) have no significant difference in male and female adult, suggesting that their expression level have no difference between sexes. This report analysis of the sialotranscripome for the WBPH, and the transcriptome provides a foundational list of the genes involved in feeding. Our data will be useful to investigate the mechanisms of interaction between the WBPH and the host plant. PMID- 27414797 TI - Novel Bioluminescent Binding Assays for Ligand-Receptor Interaction Studies of the Fibroblast Growth Factor Family. AB - We recently developed novel bioluminescent binding assays for several protein/peptide hormones to study their interactions with receptors using the so far brightest NanoLuc reporter. To validate the novel bioluminescent binding assay using a variety of protein/peptide hormones, in the present work we applied it to the fibroblast growth factor (FGF) family using the prototype member FGF2 as an example. A fully active recombinant FGF2 retaining a unique exposed cysteine (Cys) residue was chemically conjugated with an engineered NanoLuc carrying a unique exposed Cys residue at the C-terminus via formation of an intermolecular disulfide linkage. The NanoLuc-conjugated FGF2 (FGF2-Luc) retained high binding affinity to the overexpressed FGFR1 and the endogenous FGF receptor with the calculated dissociation constants of 161 +/- 21 pM (n = 3) and 25 +/- 4 pM (n = 3), respectively. In competition binding assays using FGF2-Luc as a tracer, receptor-binding potencies of wild-type or mutant FGF2s were accurately quantified. Thus, FGF2-Luc represents a novel non-radioactive tracer for the quantitative measurement of ligand-receptor interactions in the FGF family. These data suggest that the novel bioluminescent binding assay can be applied to a variety of protein/peptide hormones for ligand-receptor interaction studies. PMID- 27414799 TI - Correction: Using a Hazard Quotient to Evaluate Pesticide Residues Detected in Pollen Trapped from Honey Bees (Apis mellifera) in Connecticut. AB - [This corrects the article DOI: 10.1371/journal.pone.0077550.]. PMID- 27414798 TI - A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development. AB - The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance. PMID- 27414800 TI - Microsatellite Length Scoring by Single Molecule Real Time Sequencing - Effects of Sequence Structure and PCR Regime. AB - Microsatellites are DNA sequences consisting of repeated, short (1-6 bp) sequence motifs that are highly mutable by enzymatic slippage during replication. Due to their high intrinsic variability, microsatellites have important applications in population genetics, forensics, genome mapping, as well as cancer diagnostics and prognosis. The current analytical standard for microsatellites is based on length scoring by high precision electrophoresis, but due to increasing efficiency next generation sequencing techniques may provide a viable alternative. Here, we evaluated single molecule real time (SMRT) sequencing, implemented in the PacBio series of sequencing apparatuses, as a means of microsatellite length scoring. To this end we carried out multiplexed SMRT sequencing of plasmid-carried artificial microsatellites of varying structure under different pre-sequencing PCR regimes. For each repeat structure, reads corresponding to the target length dominated. We found that pre-sequencing amplification had large effects on scoring accuracy and error distribution relative to controls, but that the effects of the number of amplification cycles were generally weak. In line with expectations enzymatic slippage decreased proportionally with microsatellite repeat unit length and increased with repetition number. Finally, we determined directional mutation trends, showing that PCR and SMRT sequencing introduced consistent but opposing error patterns in contraction and expansion of the microsatellites on the repeat motif and single nucleotide level. PMID- 27414801 TI - Local Epidermal Growth Factor Receptor Signaling Mediates the Systemic Pathogenic Effects of Staphylococcus aureus Toxic Shock Syndrome. AB - Secreted factors of Staphylococcus aureus can activate host signaling from the epidermal growth factor receptor (EGFR). The superantigen toxic shock syndrome toxin-1 (TSST-1) contributes to mucosal cytokine production through a disintegrin and metalloproteinase (ADAM)-mediated shedding of EGFR ligands and subsequent EGFR activation. The secreted hemolysin, alpha-toxin, can also induce EGFR signaling and directly interacts with ADAM10, a sheddase of EGFR ligands. The current work explores the role of EGFR signaling in menstrual toxic shock syndrome (mTSS), a disease mediated by TSST-1. The data presented show that TSST 1 and alpha-toxin induce ADAM- and EGFR-dependent cytokine production from human vaginal epithelial cells. TSST-1 and alpha-toxin also induce cytokine production from an ex vivo porcine vaginal mucosa (PVM) model. EGFR signaling is responsible for the majority of IL-8 production from PVM in response to secreted toxins and live S. aureus. Finally, data are presented demonstrating that inhibition of EGFR signaling with the EGFR-specific tyrosine kinase inhibitor AG1478 significantly increases survival in a rabbit model of mTSS. These data indicate that EGFR signaling is critical for progression of an S. aureus exotoxin-mediated disease and may represent an attractive host target for therapeutics. PMID- 27414802 TI - Physician-Patient Communication-An Actionable Target for Reducing Overly Aggressive Care Near the End of Life. PMID- 27414803 TI - Prosocial Behavior Increases with Age across Five Economic Games. AB - Ontogenic studies of human prosociality generally agree on that human prosociality increases from early childhood through early adulthood; however, it has not been established if prosociality increases beyond early adulthood. We examined a sample of 408 non-student residents from Tokyo, Japan, who were evenly distributed across age (20-59) and sex. Participants played five economic games each separated by a few months. We demonstrated that prosocial behavior increased with age beyond early adulthood and this effect was shown across all five economic games. A similar, but weaker, age-related trend was found in one of three social value orientation measures of prosocial preferences. We measured participants' belief that manipulating others is a wise strategy for social success, and found that this belief declined with age. Participants' satisfaction with the unilateral exploitation outcome of the prisoner's dilemma games also declined with age. These two factors-satisfaction with the DC outcome in the prisoner's dilemma games and belief in manipulation-mediated the age effect on both attitudinal and behavioral prosociality. Participants' age-related socio demographic traits such as marriage, having children, and owning a house weakly mediated the age effect on prosociality through their relationships with satisfaction with the DC outcome and belief in manipulation. PMID- 27414804 TI - Effect of Preactivation on Torque Enhancement by the Stretch-Shortening Cycle in Knee Extensors. AB - The stretch-shortening cycle is one of the most interesting topics in the field of sport sciences, because the performance of human movement is enhanced by the stretch-shortening cycle (eccentric contraction). The purpose of the present study was to examine whether the influence of preactivation on the torque enhancement by stretch-shortening cycle in knee extensors. Twelve men participated in this study. The following three conditions were conducted for knee extensors: (1) concentric contraction without preactivation (CON), (2) concentric contraction with eccentric preactivation (ECC), and (3) concentric contraction with isometric preactivation (ISO). Muscle contractions were evoked by electrical stimulation to discard the influence of neural activity. The range of motion of the knee joint was set from 80 to 140 degrees (full extension = 180 degrees). Angular velocities of the concentric and eccentric contractions were set at 180 and 90 degrees/s, respectively. In the concentric contraction phase, joint torques were recorded at 85, 95, and 105 degrees, and they were compared among the three conditions. In the early phase (85 degrees) of concentric contraction, the joint torque was larger in the ECC and ISO conditions than in the CON condition. However, these clear differences disappeared in the later phase (105 degrees) of concentric contraction. The results showed that joint torque was clearly different among the three conditions in the early phase whereas this difference disappeared in the later phase. Thus, preactivation, which is prominent in the early phase of contractions, plays an important role in torque enhancement by the stretch-shortening cycle in knee extensors. PMID- 27414805 TI - FOXL2 Is an Essential Activator of SF-1-Induced Transcriptional Regulation of Anti-Mullerian Hormone in Human Granulosa Cells. AB - Anti-Mullerian hormone (AMH) is required for proper sexual differentiation by regulating the regression of the Mullerian ducts in males. Recent studies indicate that AMH could be an important factor for maintaining the ovarian reserve. However, the mechanisms of AMH regulation in the ovary are largely unknown. Here, we provide evidence that AMH is an ovarian target gene of steroidogenic factor-1 (SF-1), an orphan nuclear receptor required for proper follicle development. FOXL2 is an evolutionally conserved transcription factor, and its mutations cause blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), wherein affected females display eyelid defects and premature ovarian failure (POF). Notably, we found that functional FOXL2 is essential for SF-1-induced AMH regulation, via protein-protein interactions between FOXL2 and SF-1. A BPES-inducing mutant of FOXL2 (290-291delCA) was unable to interact with SF-1 and failed to mediate the association between SF-1 and the AMH promoter. Therefore, this study identified a novel regulatory circuit for ovarian AMH production; specifically, through the coordinated interplay between FOXL2 and SF 1 that could control ovarian follicle development. PMID- 27414808 TI - Using the iPad to facilitate interaction between preschool children who use AAC and their peers. AB - Social interaction is one of the key components of education, yet children with complex communication needs often face social isolation in the classroom, rarely interacting with same-age peers. This study investigated the impact of the provision of an iPad((r)) (1) with an AAC app with visual scene displays and a dyadic turn taking training on the number of communicative turns taken by children with complex communication needs in interaction with same-age peers. Two preschool children with complex communication needs and six peers without disabilities participated in this research. A single-subject, multiple probe across partners design with one replication was used to evaluate the effectiveness of the intervention on the frequency of communicative turns expressed by the children with complex communication needs. Parents, teachers, speech-language pathologists, and the children participated in social validation measures. As a result of intervention, Participant 1 showed immediate gains in the frequency of symbolic communicative turns after the first training session across all three partners (average gains of 30-46 symbolic communicative turns per 10-min session across peer partners). Participant 2 showed some initial gains, but they were not maintained over time (average gains of 11-24 turns across partners). Classroom implications and future research directions are discussed. PMID- 27414806 TI - Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity. AB - Hosts including humans, other vertebrates, and arthropods, are frequently infected with heterogeneous populations of pathogens. Within-host pathogen diversity has major implications for human health, epidemiology, and pathogen evolution. However, pathogen diversity within-hosts is difficult to characterize and little is known about the levels and sources of within-host diversity maintained in natural populations of disease vectors. Here, we examine genomic variation of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in 98 individual field-collected tick vectors as a model for study of within-host processes. Deep population sequencing reveals extensive and previously undocumented levels of Bb variation: the majority (~70%) of ticks harbor mixed strain infections, which we define as levels Bb diversity pre-existing in a diverse inoculum. Within-tick diversity is thus a sample of the variation present within vertebrate hosts. Within individual ticks, we detect signatures of positive selection. Genes most commonly under positive selection across ticks include those involved in dissemination in vertebrate hosts and evasion of the vertebrate immune complement. By focusing on tick-borne Bb, we show that vectors can serve as epidemiological and evolutionary sentinels: within-vector pathogen diversity can be a useful and unbiased way to survey circulating pathogen diversity and identify evolutionary processes occurring in natural transmission cycles. PMID- 27414807 TI - Airway Complications during and after General Anesthesia: A Comparison, Systematic Review and Meta-Analysis of Using Flexible Laryngeal Mask Airways and Endotracheal Tubes. AB - OBJECTIVE: Flexible laryngeal mask airways (FLMAs) have been widely used in thyroidectomy as well as cleft palate, nasal, upper chest, head and neck oncoplastic surgeries. This systematic review aims to compare the incidence of airway complications that occur during and after general anesthesia when using the FLMA and endotracheal intubation (ETT). We performed a quantitative meta analysis of the results of randomized trials. METHODS: A comprehensive search of the PubMed, Embase and Cochrane Library databases was conducted using the key words "flexible laryngeal mask airway" and "endotracheal intubation". Only prospective randomized controlled trials (RCTs) that compared the FLMA and ETT were included. The relative risks (RRs) and the corresponding 95% confidence intervals (95% CIs) were calculated using a quality effects model in MetaXL 1.3 software to analyze the outcome data. RESULTS: Ten RCTs were included in this meta-analysis. There were no significant differences between the FLMA and ETT groups in the incidence of difficulty in positioning the airway [RR = 1.75, 95% CI = (0.70-4.40)]; the occurrence of sore throat at one hour and 24 hours postoperative [RR = 0.90, 95% CI = (0.13-6.18) and RR = 0.95, 95% CI = (0.81 1.13), respectively]; laryngospasms [RR = 0.58, 95% CI = (0.27-1.23)]; airway displacement [RR = 2.88, 95% CI = (0.58-14.33)]; aspiration [RR = 0.76, 95% CI = (0.06-8.88)]; or laryngotracheal soiling [RR = 0.34, 95% CI = (0.10-1.06)]. Patients treated with the FLMA had a lower incidence of hoarseness [RR = 0.31, 95% CI = (0.15-0.62)]; coughing [RR = 0.28, 95% CI = (0.15-0.51)] during recovery in the postanesthesia care unit (PACU); and oxygen desaturation [RR = 0.43, 95% CI = (0.26-0.72)] than did patients treated with ETT. However, the incidence of partial upper airway obstruction in FLMA patients was significantly greater than it was for ETT patients [RR = 4.01, 95% CI = (1.44-11.18)]. CONCLUSION: This systematic review showed that the FLMA has some advantages over ETT because it results in a lower incidence of hoarseness, coughing and oxygen desaturation. There were no statistically significant differences in the difficulty of intubation or in the occurrence of laryngospasms, postoperative sore throat, airway displacement, aspiration or laryngotracheal soiling. However, there was a higher incidence of partial upper airway obstruction in the FLMA than in the ETT group. We conclude that the FLMA has some advantages over ETT, but surgeons and anesthesiologists should be cautious when applying the mouth gag, moving the head and neck, or performing oropharyngeal procedures to avoid partial upper airway obstruction and airway displacement. The FLMA should not be used on patients at high risk for aspiration. PMID- 27414809 TI - Recumbence Behavior in Zoo Elephants: Determination of Patterns and Frequency of Recumbent Rest and Associated Environmental and Social Factors. AB - Resting behaviors are an essential component of animal welfare but have received little attention in zoological research. African savanna elephant (Loxodonta africana) and Asian elephant (Elephas maximus) rest includes recumbent postures, but no large-scale investigation of African and Asian zoo elephant recumbence has been previously conducted. We used anklets equipped with accelerometers to measure recumbence in 72 adult female African (n = 44) and Asian (n = 28) elephants housed in 40 North American zoos. We collected 344 days of data and determined associations between recumbence and social, housing, management, and demographic factors. African elephants were recumbent less (2.1 hours/day, S.D. = 1.1) than Asian elephants (3.2 hours/day, S.D. = 1.5; P < 0.001). Nearly one third of elephants were non-recumbent on at least one night, suggesting this is a common behavior. Multi-variable regression models for each species showed that substrate, space, and social variables had the strongest associations with recumbence. In the African model, elephants who spent any amount of time housed on all-hard substrate were recumbent 0.6 hours less per day than those who were never on all-hard substrate, and elephants who experienced an additional acre of outdoor space at night increased their recumbence by 0.48 hours per day. In the Asian model, elephants who spent any amount of time housed on all-soft substrate were recumbent 1.1 hours more per day more than those who were never on all-soft substrate, and elephants who spent any amount of time housed alone were recumbent 0.77 hours more per day than elephants who were never housed alone. Our results draw attention to the significant interspecific difference in the amount of recumbent rest and in the factors affecting recumbence; however, in both species, the influence of flooring substrate is notably important to recumbent rest, and by extension, zoo elephant welfare. PMID- 27414812 TI - Predatory publishing. PMID- 27414810 TI - The Vaccination of 35,000 Dogs in 20 Working Days Using Combined Static Point and Door-to-Door Methods in Blantyre, Malawi. AB - An estimated 60,000 people die of rabies annually. The vast majority of cases of human rabies develop following a bite from an infected dog. Rabies can be controlled in both human and canine populations through widespread vaccination of dogs. Rabies is particularly problematic in Malawi, costing the country an estimated 13 million USD and 484 human deaths annually, with an increasing paediatric incidence in Blantyre City. Consequently, the aim of this study was to vaccinate a minimum of 75% of all the dogs within Blantyre city during a one month period. Blantyre's 25 administrative wards were divided into 204 working zones. For initial planning, a mean human:dog ratio from the literature enabled estimation of dog population size and dog surveys were then performed in 29 working zones in order to assess dog distribution by land type. Vaccination was conducted at static point stations at weekends, at a total of 44 sites, with each operating for an average of 1.3 days. On Monday to Wednesday, door-to-door vaccination sessions were undertaken in the areas surrounding the preceding static point stations. 23,442 dogs were vaccinated at static point stations and 11,774 dogs were vaccinated during door-to-door vaccinations. At the end of the 20 day vaccination programme, an assessment of vaccination coverage through door to-door surveys found that of 10,919 dogs observed, 8,661 were vaccinated resulting in a vaccination coverage of 79.3% (95%CI 78.6-80.1%). The estimated human:dog ratio for Blantyre city was 18.1:1. Mobile technology facilitated the collection of data as well as efficient direction and coordination of vaccination teams in near real time. This study demonstrates the feasibility of vaccinating large numbers of dogs at a high vaccination coverage, over a short time period in a large African city. PMID- 27414811 TI - Splicing Defects in the AAAS Gene Leading to both Exon Skipping and Partial Intron Retention in a Tunisian Patient with Allgrove Syndrome. AB - BACKGROUND/AIMS: Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia, and alacrima. This syndrome is caused by mutations in the AAAS gene. A major splice site mutation c.1331+1G>A was found previously in North African families affected by Allgrove syndrome. In this study, we analyzed in vivo and in silico the effect of this mutation on the splicing process. METHODS: Using reverse transcriptase polymerase chain reaction, sequencing and bioinformatics tools, we analyzed all transcripts produced by the AAAS gene containing this splice site mutation. RESULTS: The altered splicing of mRNA produces two aberrant transcripts: one with exon 14 skipping, the other with concurrent exon 14 skipping and retention of 99 bp of intron 14, both outcomes resulting in frameshifts with a new stop codon generation in the untranslated region of the last exon. Using in silico bioinformatics tools, we demonstrated that this mutation abolishes the splice donor site of exon 14 and activates a new intronic cryptic splice site in intron 14. CONCLUSION: This study demonstrated that a single splicing mutation affects the AAAS transcripts and consequently the ALADIN protein structure and function. PMID- 27414813 TI - Fetal alcohol spectrum disorders: Prevention, identification, and intervention. AB - Fetal alcohol spectrum disorders (FASD) remain a common cause of intellectual disability in infants and children, with an estimated incidence of 9.1 out of every 1,000 U.S. live births. This article discusses methods for identifying and assisting women who consume alcohol prenatally and referring infants and children with FASD for intervention. PMID- 27414814 TI - Diagnosis and treatment of familial hypercholesterolemia: The impact of recent guidelines. AB - Treatment of familial hypercholesterolemia can change the natural course of the disease to prevent premature atherosclerotic cardiovascular disease. New guidelines assist the clinician in the early identification of this common genetic disorder of lipid metabolism by placing individuals with elevated low density lipoprotein cholesterol levels in high-risk groups who benefit from treatment with statins. PMID- 27414815 TI - PTSD and depression construct: prevalence and predictors of co-occurrence in a South Lebanese civilian sample. AB - BACKGROUND: Armed conflict, occupation, and political and economic instability that are particularly experienced by the civilian Lebanese population of South Lebanon would almost inevitably affect these individuals psychologically. Therefore, identifying predictors of co-occurring mental disorders is paramount to sound assessment and intervention planning. OBJECTIVE: This study aims to determine the prevalence and predictors of co-occurring posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) in a post-war population from South Lebanon. METHOD: A total of 991 citizens from 10 villages were interviewed using a cross-sectional design through random sampling. The prevalence of PTSD, MDD, or both was 23.4%. To identify predictors of PTSD and depression co occurrence, multinomial logistic regression was used. Participants were divided into four groups (participants with no PTSD or depression, participants with PTSD only, participants with depression only, and participants with PTSD-depression comorbidity). RESULTS: Among the significant predictors of PTSD-depression co occurrence, female gender, health problems, social life events, and witnessed traumatic events were most consistently found. Additionally, employment and educational status, as well as social support, were found to significantly predict co-occurrence. CONCLUSIONS: Results reveal the distinct risk and protective factors that characterize the PTSD-depression profile. These findings will hopefully assist in the development of interventions that are sensitive to individuals' psychosocial milieu. PMID- 27414817 TI - Use of Intravenous Vancomycin and Cefepime in Preventing Endophthalmitis After Open Globe Injury. AB - PURPOSE: The choice and route of antibiotic prophylaxis in the setting of open globe injury remains controversial. We investigated the utility of intravenous vancomycin and cefepime prophylaxis in preventing endopthalmitis after open globe injury. METHODS: The charts of 224 patients who presented to Parkland Memorial Hospital and Children's Medical Center in Dallas, Texas, between June 1, 2009 and June 30, 2013, with open globe injury and who were treated with prophylactic intravenous vancomycin and cefepime were retrospectively reviewed. Data collection included time from injury to presentation, mechanism of injury, details of ophthalmological examination, timing of open globe repair, and length of follow-up. All patients were treated with intravenous vancomycin and cefepime for 48 h after presentation. RESULTS: The primary outcome measure was rate of endophthalmitis, and the secondary outcome measure was identification of risk factors for developing endophthalmitis. Out of 224 patients who presented after open globe injury, 3 patients had signs of endophthalmitis on initial exam before starting antibiotics, and 2 patients developed endophthalmitis after initiation of vancomycin and cefepime (0.9%). Delayed time from injury to presentation was a risk factor for post-traumatic endophthalmitis (P = 0.0002). The association between presence of intraocular foreign body and post-traumatic endophthalmitis was approaching significance (P = 0.064). CONCLUSIONS: When intravenous vancomycin and cefepime are used prophylactically after open globe injury, the rate of endophthalmitis is low. PMID- 27414816 TI - Pain management in trauma: A review study. AB - BACKGROUND: Pain in trauma has a role similar to the double-edged sword. On the one hand, pain is a good indicator to determine the severity and type of injury. On the other hand, pain can induce sever complications and it may lead to further deterioration of the patient. Therefore, knowing how to manage pain in trauma patients is an important part of systemic approach in trauma. The aim of this manuscript is to provide information about pain management in trauma in the Emergency Room settings. METHODS: In this review we searched among electronic and manual documents covering a 15-yr period between 2000 and 2016. Our electronic search included Pub Med, Google scholar, Web of Science, and Cochrane databases. We looked for articles in English and in peer-reviewed journals using the following keywords: acute pain management, trauma, emergency room and injury. RESULTS: More than 3200 documents were identified. After screening based on the study inclusion criteria, 560 studies that had direct linkage to the study aim were considered for evaluation based World Health Organization (WHO) pain ladder chart. CONCLUSIONS: To provide adequate pain management in trauma patients require: adequate assessment of age-specific pharmacologic pain management; identification of adequate analgesic to relieve moderate to severe pain; cognizance of serious adverse effects of pain medications and weighting medications against their benefits, and regularly reassessing patients and reevaluating their pain management regimen. Patient-centered trauma care will also require having knowledge of barriers to pain management and discussing them with the patient and his/her family to identify solutions. PMID- 27414818 TI - Histological and histochemical features of the oogenesis in the simultaneous protandric hermaphrodite shrimp Exhippolysmata oplophoroides (Decapoda: Caridea). AB - This study analyzes the dynamics of the vitellogenesis process in the simultaneous protandric hermaphrodite shrimp Exhippolysmata oplophoroides, based on light microscopic observations. The ovotestes of the shrimps at the different gonadal development stages were removed, fixed and submitted an usual histological procedure (HE) and histochemical techniques (Bromophenol Blue, PAS/Alcian Blue, and Von Kossa tests). The germinative cells were classified into oogonias, and oocytes in stages I-IV based on the following features: cell size, cytoplasm appearance, presence of yolk granules, lipid droplets, chorion, and chromatin patterns. In the male initial phase of the gonadal development, the ovotestes present mainly oogonia and oocytes I and II while in the functional hermaphrodite phase, oocytes III and IV predominate in the peripheral zone of the gonads. Oocytes with an atypical appearance of the cellular components indicative of reabsorption were also observed. This study showed an increasing accumulation of proteins, carbohydrates and lipids occurring as the germ cells develop, being the yolk elements deposited in a sequence, in which proteins and carbohydrates are the first to appear both by an endogenous as well as also by an exogenous origin. The presence of calcium was detected mainly in oocytes I, II and inside those in reabsorption, being posteriorly mobilized to chorion constitution and/or to hemolymph due to its role during molting. Although the similarity of the germ cells shape among the crustaceans, this first histochemical characterization of E. oplophoproides ovary increases the comprehension of oogenesis in a caridean simultaneous protandric hermaphrodite species. PMID- 27414820 TI - Twenty Years of SPORTS. PMID- 27414819 TI - Coming in sportsmedicine. PMID- 27414822 TI - QuikQuiz. PMID- 27414824 TI - Mixing Food and Drugs. PMID- 27414823 TI - Pearls. AB - 'Pearls' enables sports medicine professionals to share the practical tips they've developed through treating active patients. We invite you to send your contributions to Pearls Editor, THE PHYSICIAN AND SPORTSMEDICINE, 4530 W 77th St, Minneapolis, MN 55435. Selected pearls will be published, accompanied by the author's name. PMID- 27414825 TI - Scanning sports. PMID- 27414827 TI - Chronic Acromioclavicular Joint Pain. AB - In brief Chronic pain at the acromioclavicular (AC) joint can suggest several diagnoses. When evaluating a patient's pain and range-of-motion deficits, remember that an AC joint can be the sole source of discomfort. The physical exam can help rule out impingement syndrome, rotator cuff tear, scapular winging, and systemic disorders; radiographs can help exclude other pathologies. Most patients respond to conservative treatment: anti-inflammatory medications, ice massage, and activity modification. However, pain that persists 6 months or longer may warrant surgery. PMID- 27414829 TI - Combating Overuse Injuries. AB - In brief Patients with overuse injuries brief benefit from systematic diagnosis and a five-phase approach to treatment. Focusing on four chronic conditions common among children and adolescents-Little League elbow, Osgood-Schlatter disease, Sever's disease, and stress fracture-the author applies this practical stratagem for diagnosis and management. PMID- 27414828 TI - Rehabilitating at Home. AB - In brief Treatment of a patient with a brief musculoskeletal injury should include a rehabilitation program. Physicians can help patients who have relatively minor injuries rehabilitate at home by directing them through seven basic steps in which the patients regain normal range of motion, strength, endurance, power and speed, proprioception, and individual and group sport skills while maintaining their cardiovascular endurance. No special equipment is needed. PMID- 27414830 TI - Educating Athletes on HIV Disease and AIDS. AB - In brief Team physicians are in a unique brief position to counsel athletes about HIV disease and AIDS-they may be the only medical resource that this predominantly healthy group regularly encounters. A team physician who establishes rapport with athletes and has a basic knowledge of the current information on HIV disease and AIDS has a unique opportunity to frankly discuss the issues surrounding HIV transmission, both on and off the field. PMID- 27414832 TI - Infection, Immunity, and Exercise. AB - In brief How-and if-exercise alters immunity is open to debate. Research centers on changes in the number and function of granulocytes and lymphocytes and in levels of immunoglobulins. In general, these immune changes are mixed, mild, and brief. Clinical studies are inconclusive and fraught with confounders, especially the impact of psychological stress. Whether exercise enhances immunity or impairs it may, in fact, depend on whether the exercise is a joy or a stress. PMID- 27414831 TI - Difficult-to-Detect Osseous Injuries. AB - In brief MRI can prove diagnostically brief useful for a number of osseous injuries that active patients may incur. The authors weigh the benefits of MRI, such as early injury detection and excellent contrast and spatial resolution, versus its shortcomings, such as high cost and sensitivity to motion. In addition, they describe in detail the MRI appearances of stress fractures, bone bruises, occult fractures, and osteochondral fractures. PMID- 27414834 TI - 'My Dog Ate My Running Shoes'. AB - Excuses, excuses. You've probably heard hundreds of them from patients about why they don't exercise. Here's a sample of some of our favorites from friends of THE PHYSICIAN AND SPORTSMEDICINE. PMID- 27414833 TI - Mitral Valve Prolapse in Active Youth. AB - In brief Mitral valve prolapse (MVP) often brief manifests among active children and adolescents. Techniques for detecting clicks and systolic nonejection murmurs can help physicians identify MVP, and diagnostic tests can help confirm the findings. Tracking the patient's chest pain, palpitations, shortness of breath, and other symptoms can help clinicians decide if treatment should include medication-and if medication helps symptoms. Sometimes, simple reassurance will be enough to ease symptoms. With annual follow-up, patients can lead normal lives, which includes reaping the benefits of physical activity. PMID- 27414835 TI - Sports Medicine Groups 1993. AB - The following list of professional organizations and resource groups represents the growing diversity in the field of sports medicine. The list also includes government agencies, sports-related groups, and academic centers that are active in tracking sports injuries. Several entries have been updated from the list THE PHYSICIAN AND SPORTSMEDICINE published in January 1992. We have also added five new entries. The list is divided into three sections: 45 sports medicine organizations, 26 groups and committees that generate sports medicine information, and 15 statistics-gathering groups. Some groups appear more than once; they have been cross-referenced in each instance. Entries in each of the three sections have been arranged alphabetically. When appropriate, we have given the names of directors and other officers. While THE PHYSICIAN AND SPORTSMEDICINE does not endorse any of the groups listed, we do encourage readers to contact the ones that interest them. We have included only the essential information about each group; more detailed descriptions can be obtained by calling or writing to the particular group you are interested in. Readers who would like their organization to be added to next year's list should contact THE PHYSICIAN AND SPORTSMEDICINE Organizations Project, 4530 W 77th St, Minneapolis, MN 55435. PMID- 27414836 TI - Eight Programs to Consider. AB - Exercise videos allow patients to improve overall fitness in the comfort of their own homes. But cutting through the Hollywood glitz and hype that surround this lucrative fitness market is difficult. Here are one exercise physiologist's recommendations for exercise videos for patients at various fitness levels. PMID- 27414837 TI - The Smart Way to Shovel Snow. PMID- 27414838 TI - Employment Opportunities. PMID- 27414840 TI - Highly Efficient, Reproducible, Uniform (CH3 NH3 )PbI3 Layer by Processing Additive Dripping for Solution-Processed Planar Heterojunction Perovskite Solar Cells. AB - A processing additive dripping (PAD) approach to forming highly efficient (CH3 NH3 )PbI3 (MAPbI3 ) perovskite layers was investigated. A MAPbI3 (CB/DIO) perovskite film fabricated by this approach, which included briefly dripping chlorobenzene incorporating a small amount of diiodooctane (DIO) during casting of a MAPbI3 perovskite precursor dissolved in dimethylformamide, exhibited superior smooth, uniform morphologies with high crystallinity and large grains and revealed completely homogeneous surface coverage. The surface coverage and morphology of the substrate significantly affected the photovoltaic performance of planar heterojunction (PHJ) perovskite solar cells (PrSCs), resulting in a power conversion efficiency of 11.45 % with high open-circuit voltage of 0.91 V and the highest fill factor of 80.87 %. Moreover, the PAD approach could effectively provide efficient MAPbI3 (CB/DIO) perovskite layers for highly efficient, reproducible, uniform PHJ PrSC devices without performance loss or variation even over larger active areas. PMID- 27414841 TI - Pathogenesis of Hyperhomocysteinemia-New Insights. AB - Mild to moderately elevated levels of homocysteine (Hey) in plasma, denoted as hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in coronary, cerebral and peripheral vessels, as well as for arterial and venous thromboembolism. Despite its clinical significance, the molecular mechanism of homocysteine's effects is not yet clearly defined. Most of the effects of homocysteine that have been demonstrated in vitro, affecting endothelial function have been attributed to the oxidant reactivity of this molecule, which is shown to affect the vasoregulatory and thrombotic/fibrinolytic function of endothelium. However, the relevance of these observations to the clinical situations is questionable, since excessively high concentrations of homocysteine are used in most of the experiments. We have observed that homocysteine, at physiologically relevant concentrations, specifically induces the expression of tissue factor by monocytes, and a non specific redox effect is not involved. Tissue factor expression by monocytes is mediated by increased intracellular concentrations of the metabolic intermediate, S-adenosylhomocysteine, which is a potent inhibitor of methyl transferases. These studies suggest that tissue factor expression by circulating monocytes by intracellular perturbations may be a plausible mechanism by which homocysteine may induce thrombosis. PMID- 27414842 TI - 6-Mercaptopurine, Still Valuable for the Palliative Treatment of Acute Myeloid Leukaemia. AB - Although 6-mercaptopurine (6-MP) is frequently used in the treatment of acute myeloid leukaemia (AML), its effect on disease progression has not been studied systematically. In a small retrospective analysis, we found that 6-MP could induce marked haematological improvement in a considerable number of AML patients who were not treated with intensive remission induction courses. Due to the inherent limitations of retrospective analyses, we then investigated prospectively in 51 consecutive patients over a 3-year period in a single centre, to what extent, oral 6-MP 250 mg twice a week could be beneficial to AML patients who were not-or no longer-eligible for intensive chemotherapy. Clinical response was scored according to changes in blood cell counts and dependency on blood transfusions. Thirteen patients (25%) were considered responders since they showed an increased platelet count from the first month after initiation of 6-MP onwards and they became independent of blood transfusions after 3 months. This effect lasted for 13 (range 7-30+) months. Median overall survival of this subgroup was 16.5 (6-33+) months. Ten patients (20%) had a shorter or incomplete response and a survival of 12 (6-30) months. Seven patients were lost to follow up. Twenty-one (41%) failed to respond and survived for 4 (1.5-17) months. The response seemed not to be affected by previous chemotherapy, history of myelodysplasia, or karyotype abnormalities, but high leukocyte count initially was unfavourable. 6-MP thus can induce marked improvement of blood cell counts in a considerable proportion of AML patients who are not eligible for intensive chemotherapy, leading to good quality of life and a significant prolongation of survival. PMID- 27414843 TI - Abnormalities of the p53 Tumour Suppressor Gene in Mature B-cell Neoplasms. AB - The p53 gene, located on the short arm of human chromosome 17 at 17p13, codes for a 393 aminoacid phosphoprotein, which acts as a transcription factor and is involved in the control of many different cellular processes. It is the most frequently mutated gene in neoplasia and mutations have been observed in 231 of the 393 codons, including all but one codon of the DNA binding domain. p53 abnormalities in mature B-cell lymphoproliferative disorders (B-LPDs) occur in up to 75% of cases and are mostly detected in patients with advanced clinical stages. B-LPDs encompass a heterogeneous group of clinically important lymphoid malignancies with a complex biology, varying natural history and prognosis that makes their classification and treatment difficult. Despite many publications concerning the role of p53 abnormalities in the development of B-LPDs and the prognostic implications of detecting aberrant p53 function, it is difficult to draw firm conclusions as studies have varied with respect to patient selection and classification and techniques used. This review focuses on the available data pertaining to p53 abnormalities in the different mature B-cell neoplasms and summarises the incidences of abnormalities, the mutation patterns encountered and their clinical significance. PMID- 27414844 TI - Assessment of Apoptosis Regulating Factors BCL-2 and Fas Antigens on Malignant and Normal Plasma Cells. AB - Multiple myeloma (MM) is characterised by slow proliferation of malignant plasma cells and their accumulation within the bone marrow. The dysregulation of programmed cell death (apoptosis) is a very important mechanism in the pathogenesis of this tumour. It prompted us to investigate the apoptosis regulating factors such as the pro-apoptotic Fas antigen and the anti-apoptotic protein BCL-2 on bone marrow malignant plasma cells in untreated patients with newly diagnosed MM and to compare them with their normal counterparts-plasma cells isolated from bone marrow of healthy individuals. Twenty-nine MM patients and 16 healthy persons were studied. Bone marrow mononuclear cells were isolated, indicated by monoclonal antibodies and analysed using the flow cytometry method. There was no statistically significant difference in BCL-2 expression in plasma cells between patients and control groups. However the percentage of BCL-2 positive cells was significantly related to the clinical stage of the disease. We detected statistically significant lower percentage of Fas positive cells in the patient group than in control. We concluded that in MM at diagnosis the expression of BCL-2 in bone marrow malignant plasma cells was comparable to normal plasma cells but expression of Fas antigen on these cells was lower. It suggests that down regulation of Fas and normal regulation of BCL-2 may be implicated for myeloma cell survival and their escape from apoptosis in vivo. PMID- 27414845 TI - Treatment of Relapsing Ph+ Acute Lymphoblastic Leukemia with Donor Leukocyte Infusion Followed by Quantitative Monitoring of Residual Disease. AB - The case of a 34-year-old man with relapsing Ph+ acute lymphoblastic leukemia (ALL), which occurred five months after allogeneic bone marrow transplantation, is described. He was originally treated with aggressive chemotherapy, which put him in hematological remission, and he subsequently received donor leukocyte infusion (DLI) form the original donor. To assess the efficacy of this adoptive immunotherapy, we monitored minor-BCR/ABL (m-BCR/ABL) mRNA levels using the recently established real-time quantitative RT-PCR (RQ-PCR) assay. The results were compared with those obtained using conventional qualitative RT-PCR assays run in parallel. RQ-PCR, but not RT-PCR-based, minimum residual disease (MRD) detection showed a good correlation with the rapid changes documented during the post-DLI clinical course. Currently, six months after DLI, the patient continues to be in remission, which is consistent with the undetectable levels of m-BCR/ABL mRNA in the leukemic clone using RQ-PCR found in this study. Thus, monitoring of m-bcr/abl transcripts using RQ-PCR provides more useful information on a clinical assessment of MRD. PMID- 27414846 TI - Relapsed Acute Lymphoblastic Leukemia Presenting as Optic Neuritis. AB - Leukemic infiltration of the optic nerve is rare [1]. [Camera, A., Piccirillo, G., Tranfa, F., Rosa, N., Frigeri, F., Martinelli, V., Rotoloi, B. (1993) "Optic nerve involvement in acute lymphoblastic leukemia", Leuk. Lymph. 11, 153-155]. Radiotherapy should be given urgently to all patients with optic nerve infiltrate to restore their vision [2]. [Rosenthal, A. (1983) "Ocular manifestation of leukemia", Ophthalmology 90, 899-905]. We report a case of a unilateral optic nerve relapse 7 months after diagnosis of acute lymphoblastic leukemia (ALL) in a 17-year-old boy who had been off treatment for 6 weeks. The ocular symptoms was initially diagnosed as primary optic neuritis and treated with corticosteroids resulting in temporary clinical recovery. Radiation therapy for ocular leukemia that was commenced 2 months after the onset of symptoms failed to reverse the visual loss. The lack of a reliable and effective tool to diagnose ocular leukemia at an early stage has resulted in significant treatment delay and poor visual outcome. PMID- 27414847 TI - Cytokines and Cytomegalovirus Disease Following Allogeneic Bone Marrow Transplantation. AB - Cytomegalovirus (CMV) disease (interstitial pneumonia and encephalitis) is an important complication of bone marrow transplantation. We monitored cytokine, adhesion molecule, and chemokine levels from before conditioning until the early stage after allogeneic bone marrow transplantation in 15 procedures where recipients or donors were seropositive for CMV. Results were compared between the patients with symptomatic, asymptomatic CMV, and no CMV. All four patients with CMV disease had fever during the aplastic phase after bone marrow transplantation and all of them showed a marked increase of tumor necrosis factor-alpha, interferon-gamma, and interleukin-8 at the time of leukocyte recovery (p<0.05; two-way layout analysis of variance). Patients without CMV disease despite of reactivation of the virus, showed a significant increase of interferon-gamma p<0.05; two-way layout analysis of variance), but there was no rise of tumor necrosis factor-a or interleukin-8. Cytomegalovirus-negative patients showed no increase of any of these cytokines. Elevation of these three cytokines may cause CMV replication, and inflammation during the aplastic phase may promote such a cytokine increase. Our findings suggest that a marked increase of interferon gamma, tumor necrosis factor-alpha, and interleukin-8 during engraftment after bone marrow transplantation may be related to CMV disease. PMID- 27414848 TI - A Case of Childhood Anemia Complicated by a Red Cell Membrane Sugar Chain Anomaly with Low Levels of Sialic Acid. AB - An 8-year-old girl presented with the pallor and purpura. She was diagnosed to suffer from anemia of an unknown cause with leukocytopenia and thrombocytopenia. The patient's red cells showed marked agglutination with peanut lectin (PNA), and erythroblasts forming CFU-E in the bone marrow reacted positively to avidin labeled PNA on enzyme immunohistochemistry, suggesting an abnormality of sugar chain on red cell and also erythroblast membranes. Membrane O-glycan sugar chains of her red cells showed a low level of sialic acid on high performance liquid chromatography (HPLC). Her anemia failed to respond to the corticosteroids, gamma globulin, recombinant erythropoietin (rhEPO), and recombinant granulocyte colony stimulating factor (G-CSF), and frequent red cell transfusion was required. After 6 years, the patient underwent an unrelated bone marrow transplantation (U-BMT). From 2 weeks after transplantation, the PNA reactivity of her red cells decreased and then disappeared and the red cell membrane antigens changed to the donor type after 4 weeks. These results suggested that the sugar chain abnormality causing low levels of sialic acid in the red cell membrane was already present on erythroid progenitor cells in the bone marrow. PMID- 27414850 TI - Lenalidomide for the treatment of B-cell lymphoma. AB - INTRODUCTION: Although the combination of an anti-CD20 monoclonal antibody and chemotherapy has widely improved survival of patients with B-cell lymphoma, the disease still relapses. A better understanding of the biology of lymphomas has highlighted the role of the cell of origin in response to treatment and outcome. Lenalidomide represents an attractive therapeutic option due to its original mechanism of action. AREAS COVERED: In this review, the authors describe the pharmacological properties of lenalidomide, and the rational for its use in B cell lymphomas; focusing on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). They discuss the mechanism of action of the drug and its current and future clinical development. They also review the current data in relapsed/refractory situations as well as in first line treatment. EXPERT OPINION: Lenalidomide is an oral non-chemotherapy immunomodulatory agent with an acceptable toxicity profile and manageable side effects. Efficacy has widely been demonstrated, especially in MCL, FL and non Germinal Center DLBCL patients. Further studies are now warranted to better define the strategy for the use of lenalidomide in B-NHL patients, and clarify which subgroup of patients will really benefit of lenalidomide as part of first line treatment or in a relapsed/refractory setting. PMID- 27414851 TI - Role of STIM1 in the surface expression of SARAF. AB - The store-operated Ca2+ entry-associated regulatory factor (SARAF), a protein expressed both in the endoplasmic reticulum and the plasma membrane, has been presented as a STIM1-interacting protein with the ability to modulate intracellular Ca2+ homeostasis. SARAF negatively modulates store-operated Ca2+ entry (SOCE) by preventing STIM1 spontaneous activation and regulating STIM1 Orai1 complex formation. In addition, SARAF is a negative regulator of Ca2+ entry through the arachidonate-regulated Ca2+ (ARC) channels. Here we explored the possible role of the surface expression of SARAF on the location of STIM1 in the plasma membrane. In NG115-401L cells, lacking a detectable expression of native STIM1, transfection with pHluorin-STIM1, which is able to translocate to the cell surface, enhances the plasma membrane location of SARAF as compared to cells transfected with YFP-STIM1, lacking the ability to translocate to the cell surface. These findings suggest that the surface location of SARAF is dependent on the expression of STIM1 in the plasma membrane. PMID- 27414852 TI - Back to nursing. AB - Every year around 30,000 qualified nurses leave the NHS. Many of them never come back. That statistic is becoming familiar, but its implications are only slowly dawning on the policy-makers, let alone the public. PMID- 27414853 TI - Strike action is no solution. AB - Public opinion in recent years has always been solidly behind the NHS and the dedicated staff who work in it. Not least has been the esteem in which nurses are held. But it would be wrong, and even dangerous to take that appreciation for granted. PMID- 27414855 TI - Stoma nurses 'need training in sexual counselling skills'. AB - Sexual counselling, as with any other counselling, relies upon the skill of the counsellor not only to be at ease with the subject matter but to be knowledgeable in it, delegates at a conference for stoma nurses heard. They were helped to feel at ease with this often difficult role of the stoma nurse, by Bridgid Breckman, herself a stoma nurse and counsellor. PMID- 27414856 TI - Cancer awareness drive. AB - Cancer of the bowel, the second most common cause of death in the United Kingdom, can be cured if detected early enough. But at present only one in three people treated by the NHS for bowel cancer survive, because the disease is found too late. PMID- 27414857 TI - Bad news. AB - 'I am a disillusioned and dispirited working mum with over 20 years' experience in the NHS. PMID- 27414858 TI - Good news. AB - I have always been a dreamer. When I started nursing in the early 1950s, I was convinced I would be a ward sister by the time I was 23, and a matron by 26. Six months after I completed my training, I married. All dreams of becoming a matron were forgotten and I concentrated on the latest one, a home and family. This materialised, but to the exclusion of my career. PMID- 27414860 TI - New cancer treatment outlined by experts. AB - New radiotherapy and chemotherapy treatment regimes were explained to a group of practice nurses last week in a visit to a regional radiotherapy centre and talks from expert nurses and doctors. PMID- 27414859 TI - Untitle. AB - Nurses involved in caring for the elderly examine some of the material used in Reminiscence Therapy - the use of visual aids, posters, photographs, and popular music from earlier days which can encourage communication and help develop a sense of reality in elderly people cared for in long stay institutions. PMID- 27414861 TI - Practice nurses are 'best resource' for detecting cervical cancer. AB - Practice nurses should be seen as the best resource for the detection and prevention of cervical cancer, according to Consultant Obstetrician and Gynaecologist Harry Gordon from Northwick Park Hospital. PMID- 27414863 TI - Women suffer in silence. AB - Women with stress incontinence commonly believe that nothing can be done to help them, according to a study from Basingstoke. PMID- 27414862 TI - Specialist support for diabetics. AB - The drug company Ely Lilly is paying the salaries of three diabetes nurse specialists for one year to ensure good support for patients. PMID- 27414865 TI - Untitle. AB - Nurses and occupational therapists try out patient lifting equipment at a study day last week, held by the Disabled Living Foundation. The DLF keeps a range of staff and patient aids for demonstration and is happy to offer advice on the equipment and resources available. The Disabled Living Foundation is based at 380/384 Harrow Road, London W92HU. Telephone 01 -2896111. PMID- 27414864 TI - Preparing your path. AB - Anyone with the magic letters RGN (or alternatives) after her name can pin on her cap, tie her apron strings and let herself loose on unsuspecting patients - however many years have passed since she last took a temperature. This sounds like an easy return to nursing, but it is bad news for nurse and patient. PMID- 27414866 TI - Invisible PMS problems. AB - Many women are discouraged from broaching the subject of premenstrual syndrome because doctors have told them there is nothing wrong, according to health educator Lesley Mabbell. PMID- 27414867 TI - NW thames fun and games. AB - A pilot study which introduced mental handicap nurses to structured play is to become a permanent feature of North West Thames' mental handicap service. PMID- 27414868 TI - Disposable insulin syringes 'safe for re-use'. AB - Research in America has reinforced the belief that disposable insulin syringes can safely be reused, providing if is by the same patient and in their [Illeligble Word] home. PMID- 27414869 TI - Research reveals virus. AB - Researchers from Liverpool have shown that a virus is involved in breast cancer. PMID- 27414871 TI - Respiratory monitoring. AB - Monitoring neonatal respiratory rates decreases mortality from septicaemia caused by group B streptococci, according to a study from Middlesex. PMID- 27414870 TI - Measles immunisation. AB - Health visitors and general practitioners have a poor knowledge of the Department of Health and Social Security's guidelines on measles immunisation, according to research from Kent. PMID- 27414872 TI - The importance of eating. AB - What children eat is as important as the way they eat it, according to a study of underweight children from inner London. PMID- 27414873 TI - Assessing pain control. AB - Misunderstandings about addiction, tolerance and the importance of taking drugs at the prescribed times all contribute to cancer patients' pain control, according to research from America. PMID- 27414874 TI - Facing a challenge. AB - Caring for people with 'challenging behaviour' is one of the most difficult aspects of mental handicap nursing. There is still a feeling that for this minority group, care in the community will never be a realistic option. PMID- 27414877 TI - Strikers 'could be struck off register' UKCC warns. AB - Nurses who take industrial action could be struck off the register, the UK Central Council for Nursing, Midwifery and Health Visiting has warned. PMID- 27414875 TI - Getting that job. AB - The initial, and perhaps f the biggest, obstacle I facing the nurse who facing wants to return to work is summoning up the confidence. The clinical work itself will seem daunting after a long break, but so does the process of getting the job in the first lace. Nevertheless there is a lot you can do to help yourself forewarned is forearmed. PMID- 27414878 TI - Strike condemned. AB - Mrs Thatcher has condemned strikes in Scotland against privatisation as being 'at the expense of patients'. This followed nurses joining ranks with hospital ancillary workers in Lothian and Lanarkshire last week to protest against plans to put catering and domestic services out to private tender. PMID- 27414879 TI - Opportunity KnocksNew hospitals and services can provide exciting job opportunities for qualified nurses. This regional round up lists health authorities who have contacted Nursing Standard with information about their latest projects. Is there something here for you? PMID- 27414880 TI - Unions meet over pay rise claims. AB - Staff side unions in the London Weighting Consortium meet this week to discuss how to pursue claims for a I,000 rise, but members of COHSE are already balloting on strike action over the issue. PMID- 27414882 TI - Former top tory urges cash boost. AB - A former top Cabinet Minister urged the Government to at least double and possibly treble its increase in NHS spending. PMID- 27414883 TI - UKCC withdraws members quorum clause. AB - A controversial clause reducing the number of members required to sit on Professional Conduct Committee cases has been withdrawn by the UK Central Council for Nursing, Midwifery and Health Visiting. PMID- 27414881 TI - Call for public health liaison. AB - A new report calling for a director of public health in each health authority to co-ordinate advice and disease prevention has been welcomed by the Royal College of Nursing and the Health Visitors Association. PMID- 27414884 TI - National board nominations. AB - Nominations are coming in for the election of new members to the National Boards for Nursing, Midwifery and Health Visiting. PMID- 27414885 TI - Community nurses angry With child benefit freeze. AB - Community nurses have reacted angrily to the news that the Government is to go ahead with a freeze on child benefit. PMID- 27414886 TI - More cardiology services needed. AB - Thousands of people the every year because the cardiology services provided by district hospitals are inadequate, according to a report published last week. PMID- 27414887 TI - Mass staff protest in north west. AB - Hospital staff throughout the North West region are to hold a day of mass protest at cuts in health services next month. PMID- 27414888 TI - Useful addresses. AB - Chief Nursing Officer, Welsh Office, New Crown Building, Cathays Park, Cardiff CF1 3NG, tel: 0222 825111 (recruitment). PMID- 27414889 TI - What's new in nursing. AB - Things are moving fast in nursing - partly in response to changing patterns in society, and in health care itself. These are taking nursing far beyond its old role of carrying out (without question) the orders of doctors. PMID- 27414890 TI - Radical reforms call. AB - A new report from the Centre for Policy Studies claims that facilities for National Health Service patients are so poor that 'it is doubtful whether long stay prisoners in maximum security gaols fare much worse'. PMID- 27414891 TI - Opinion divided over abortion bill. AB - Both the pro and anti abortion campaigns surrounding Liberal MP David Alton's Private Members Bill are gearing up their activities. PMID- 27414893 TI - Nursing on the australian trail. AB - Sharks, crocodiles, spitting spiders and army rations were just some of the health hazards encountered by Accident and Emergency Staff Nurse Linda Mutti on her recent trip to the Australian island of Badu with Operation Raleigh. PMID- 27414892 TI - Christian care for aids victims. AB - A North London charitable Christian hospital has become the first such institution to provide hospice care for people with AIDS. PMID- 27414894 TI - Useful publications. PMID- 27414895 TI - Unions fight on over pay. AB - The announcement that the Government is to leave any decision on changes in special duty payments to the nurses' Pay Review Body has by no means placated the unions. PMID- 27414896 TI - Meningitis spread is puzzling. AB - New research studies are beginning to shed some light on the mysterious and rapid spread of the meningitis disease, as health visitors and community nurses receive warnings to be particularly vigilant. PMID- 27414897 TI - Tough talks at wessex orthopaedic meeting. AB - Members of the RCN Wessex Orthopaedic Group set the New Year off to a challenging start when they tackled the issues of clinical grading and the role of the specialist nurse at their recent meeting. PMID- 27414898 TI - Sheila marson retires. AB - Sheila Marson, leading nurse educationalist and previously active as a tutor within the RCN's Association of Nursing Education, is retiring in March after 42 years in nursing. PMID- 27414900 TI - En adviser ready to 'face flak'. AB - Susan Scott, the Royal College of Nursing's new Nurse Adviser for Enrolled Nurses, is ready to face her 'share of flak' given that the future of ENs has been such a controversial issue in the last 12 months. PMID- 27414899 TI - Informative report follows international oh congress. AB - An informative report on last year's International Congress on Occupational Health in Sydney, Australia was given to the Merseyside and Wirral group of the RCN's Society of Occupational Health Nursing at their recent meeting. PMID- 27414901 TI - Brighton elections will be hotly contested. AB - The important position of chairman of RCN Congress for 1989-90 will be hotly contested by five candidates at the election before this year's Brighton event in May. PMID- 27414902 TI - Interest group affiliated. AB - The Ear Nose and Throat Nursing Interest Group is now officially affiliated to the RCN's Association of Nursing Practice. As a College special interest group several events are planned for 1988, including a national conference at Keele University on April 16 and 17. Members plan to continue to promote ENT nursing and to share information and ideas through regular regional meetings and a newsletter to be published three times a year. Regional groups will later be established in the South West and in Scotland. PMID- 27414903 TI - Regional focus. AB - A new nursing recruitment and retention unit is to be established for the South East Thames region, Audrey Emerton, Director of Administration, Personnel and Training, and Regional Nursing Officer has announced. PMID- 27414904 TI - Computer forecasting scheme spreads throughout south east thames. AB - A new computer-based system for forecasting 24 hours ahead how many nurses will be needed on the wards is being expanded from its original pilot in Greenwich HA to other districts and ultimately throughout the South East Thames region. PMID- 27414905 TI - Eastbourne nurses return bonus insult. AB - Hundreds of Eastbourne nurses received what they called an 'insulting' 50 pence Christmas bonus - and promptly sent it back to management. PMID- 27414906 TI - Brighton nurse wins compensation. AB - A Brighton nurse has received L10,000 interim compensation with more to follow for a back injury she sustained just nine months into her student training as a pupil nurse. PMID- 27414907 TI - Gwynedd plans to cut nursing services. AB - Gwynedd Health Authority wants to save L450,000 over the next three years by cutting the nursing shift overlap and restructuring skill mix. PMID- 27414908 TI - Self defence for oldham nurses. AB - Accident and Emergency nurses at Oldham Royal Infirmary are to be taught self defence by Britain's leading woman exponent of martial arts. This follows an increasing number of incidents in their unit where drunken friends or relatives of patients have attacked or verbally abused nurses, often at night when the three nurses on duty may be coping with 60 [Illegible word] and those accompanying them. PMID- 27414909 TI - Norwich stages courses with a difference. AB - A back to nursing course with a difference is due to start this spring in Norwich HA. PMID- 27414911 TI - Watchdog. PMID- 27414910 TI - Birmingham appoints paediatric tutor. AB - Central Birmingham Health Authority last week confirmed that a tutor has been appointed to teach a new paediatric intensive care course, which will provide places for twelve nurses each year. PMID- 27414912 TI - Directions. AB - The provision of nursing care for the elderly is one area of the profession that carries a high level of personal initiation and ultimately a greater degree of job satisfaction for the nurses involved. Only they are able immediately and knowledgably to dispel the unfounded myths of the inexperienced eg, if you were to ask a nurse who has worked with elderly people for any length of time whether 'they' are 'more difficult' patients, the answer 'No more difficult than any other patient' comes back without hesitation. PMID- 27414914 TI - Caring for boby and soul. AB - Fannie Storr's sudden decision to move to the new and unusual post of Health Development Officer with the United Society for the Propagation of the Gospel caused some surprise to those nurses who knew her as the thoughtful and committed Director of Gloucestershire School of Nursing. PMID- 27414913 TI - A bill of contention. AB - This Friday (January 22) David Alton's Private Members' Bill, which seeks to reduce the legal time limit for abortions to 18 weeks of pregnancy, is due to get its second reading. PMID- 27414915 TI - New bill to fight against child abuse. AB - Moves to give health visitors greater powers in suspected cases of child abuse were laid before Parliament last week. PMID- 27414916 TI - Health care managers call for NHS tax boost. AB - Chancellor of the Exchequer Nigel Lawson has come under fire from NHS finance officers and treasurers who want a share of I his proposed tax cuts to help fully fund I nurses' pay awards. PMID- 27414917 TI - MP's outburst dashes hopes of commons tv. AB - Parliamentary protests over health cuts [Illegible word] have unwittingly brought about an-[Illegible word] casualty - the prospect of televising the House of Commons. PMID- 27414918 TI - PM acts over asian baby abortion claims. AB - Prime Minister Margaret Thatcher has stepped into the row over allegations that Asian babies are being aborted because they are the wrong sex. PMID- 27414919 TI - Alton confident about amendment bill. AB - If Home Secretary Douglas Hurd's attempt to defeat Tory backbencher Richard Shepherd's bid to reform the Official Secret's Act succeeds, it could speed up the political passage of David Alton's Abortion amendment bill. PMID- 27414920 TI - Coping with Life on Insulin J Steel M Dunn Coping with Life on Insulin Chambers 134pp L2.95 0-550-20514-4 [Formula: see text]. AB - Here is a practical, down to earth book aimed at helping the one in 1,000 British insulin- dependent diabetics. Judith Steel and Margaret Dunn write in a clear, easily readable style that does not 'talk down' to its audience. PMID- 27414921 TI - Drug Management for Nurses G Downie A Mackenzie A Williams Drug Management for Nurses Churchill Livingstone 218pp L6.95 0-443-0346-8 [Formula: see text]. AB - Most pharmacology books for nurses neglect to include information on the practicalities of drug therapy; this one provides it in detail. It ranges from a description of the value of computers in organising hospital and community pharmaceutical services to the daily management of controlled drugs with order form and stock balance record examples. PMID- 27414922 TI - A Dictionary of Pastoral Care edited by A Campbell Campbell A A Dictionary of Pastoral Care SPCK 320pp L12.50 0-281-04239-X [Formula: see text]. AB - Although purporting to be a dictionary, Alistair Campbell's book is in fact a mini encyclopaedia. It aims to provide a concise but comprehensive guide to the concepts and problems most likely to be encountered in pastoral care, reflecting as well new approaches to education and counselling. PMID- 27414923 TI - Families of the Mentally III Hatfield A Lefley H Families of the Mentally III Cassell 336pp L14.95 0-304-31422-6 [Formula: see text]. AB - Agnes Hatfield and Harriet Lefley draw on expertise from the fields of psychology, education, nursing, psychiatry and rehabilitation to produce a graphic account of the effects mental illness has on families and the ways in which they cope. Underlying assumptions about causation of severe mental illness are challenged and the focus switches from the 'why?' to the 'so what happens now?', which seems to me a more productive approach. PMID- 27414924 TI - Don't start here. AB - 'Because we admire nurses we mustn't believe that everything they say is right.' So says Woodrow Wyatt (aka The Lord Wyatt of Weeford), the News of the World's self-styled 'Voice of Reason.' PMID- 27414925 TI - If the cap fits... AB - Still on the subject of our uniforms competition, it was fascinating to read all the entries and gauge the current state of opinion. One contentious issue was - surprise, surprise - caps. PMID- 27414926 TI - Uniform unveiled. AB - Next week we unveil our hard- won shortlist of readers' designs for a new nursing uniform. PMID- 27414927 TI - Long John Sister. AB - In the good old days, nurses' homes had a home sister who looked after you...or had a good old snoop round your room, depending on what sort of person she was. One nurse recalls a pet-loving sister he had. It was bad enough to be called to the door every night to be told it was lights out in ten minutes. PMID- 27414928 TI - Diary strictly off the record. AB - Our roundup of what's on. PMID- 27414929 TI - Lack of choice. AB - I would like to make a comment, in light of my own experience concerning Colin Ralph's letter about UKCC reregistration fees (Nursing Standard week ending January 2). He states that the majority of practitioners support the move to periodic reregistration. I would argue with this statement. Nurses are paying because failure to do so means loss of registration, therefore loss of right to practice, therefore loss of means to earn a living. Because I believe this to be undemocratic I refused to pay. PMID- 27414931 TI - Pillow talk. AB - I am a Registered General Nurse presently undertaking English National Board Course No 100 (on General Intensive Care Nursing at Guy's Hospital, London. I was most intersted in the article entitled 'Take Away Pillows' which appeared in the Nursing Standard week ending October 3,1987.1 have therefore decided, as my major assignment project, to research into people's attitudes and opinions on the use of pillows as head and neck support when attempting resuscitation procedures. PMID- 27414930 TI - Positive features. AB - I feel drawn to respond to the letter from David Harding- Price entitled 'Alternative NHS Funding' which appeared in the Nursing Standard of January 9, 1988. PMID- 27414932 TI - The other side of the coin. AB - I am writing in response to Sue Haworth's letter in the Nursing Standard (week ending December 5) with regards to reduced RCN membership fees for undergraduate student nurses. PMID- 27414933 TI - Nothing left. AB - There have been many letters and much comment in the Nursing Standard arid national newspapers on the subject of nurses' pay, including special duty payments. PMID- 27414934 TI - Ashamed to be a nurse. AB - The recent strike by nursing staff belonging to NUPE widely publicised by the media must cause the nursing profession to lose the respect of the general public. They know nurses are poorly paid and the NHS is in a poor state. PMID- 27414935 TI - Curious statement. AB - Your profile on the nurse pratitioner scheme at Oldchurch Hospital in the Standard (week ending December 12) contained a curious statement, namely that the experienced nurse in Accident and Emergency cannot refer patients to a social worker. This appears rather odd to me since anyone from the public can contact a social worker when needed. PMID- 27414936 TI - Taking exception. AB - The letter from D F Jesset (Nursing Standard week ending January 2) in response to the articles concerning Mrs Guinette Davies sounds as though that person has taken exception to the statements made by Mrs Davies. PMID- 27414937 TI - Kenya. AB - The Government in Kenya has made AIDS a reportable disease, so that doctors will soon be required to supply the names and addresses of AIDS patients to the Ministry of Health, according to a recent report by the country's National Committee on AIDS. Meanwhile, a five year programme has been launched to control the spread of AIDS in Kenya where the number of reported cases has risen to 625 since 1983. PMID- 27414939 TI - Iceland. AB - Midwives play a major role in keeping Iceland's infant mortality rate the lowest in the world. PMID- 27414938 TI - Soviet union. AB - In the USSR, the national health care system is to be given an overhaul following the release of a document by the Soviet government. The report is the result of several months of nationwide consultation and contains a review of existing services as well as suggestions for improvements. PMID- 27414940 TI - United states. AB - The newly formed National Centre for Nursing Research at the National Institute of Health, Bethesda in Maryland, USA has appointed Dr Ada Sue Hinsaw as its first director. Her job is to follow the mandate set by the US Congress to work on basic and applied research relative to patient care, promotion of health and prevention of illness. PMID- 27414941 TI - Australia. AB - The Health Commission in South Australia has decided to install $1.5 million worth of micro computers in the states larger rural and smaller urban hospitals in order to give nurses more time for increased patient contact. PMID- 27414942 TI - Soldiering on. AB - When she isn't delivering babies or working in the special baby care unit, Beverley is learning how to unload guns and read maps. PMID- 27414943 TI - Listings. AB - Nursing Standard's listings section is a completely free service for its readers. To ensure maximum publicity for any event connected with your profession, be sure to let us know so that it can be included in our exhaustive nationwide guide to what's on in nursing. PMID- 27414944 TI - Dry skin treatment. AB - Coal tar is back in fashion as a treatment for dry skin conditions with a new shampoo and bath oil on the market. PMID- 27414945 TI - Sore skin remedy. AB - Calendula ointment, the traditional homeopathic remedy for sore skin, is now widely available at retail outlets, its manufacturers Weleda say. The ointment has antiinflammatory, antiseptic and antibacterial properties and can be used for sore nipples in nursing mothers and ulcerated skin. PMID- 27414947 TI - Walking aid for children. AB - A new walking aid for children is to be launched this winter by Gerald Simonds Wheelchairs. PMID- 27414946 TI - One step pregnancy test. AB - Women who want to know whether they are pregnant now have to wait only five minutes for a home test result. PMID- 27414948 TI - Curved surgical stapler for easy surgery. AB - A surgical stapler designed for circular anastomosis in gastro intestinal surgery will offer major advances for surgeons, say its manufacturers. PMID- 27414949 TI - Safe needle disposal without recapping. AB - A sharps disposal unit which allows destruction of needles with out recapping them has been launched by the Beaumaris Instrument Company. PMID- 27414950 TI - Hyper Active. PMID- 27414951 TI - On the fractality of the Freundlich adsorption isotherm in equilibrium and non equilibrium cases. AB - We investigate the relationship between the Freundlich adsorption exponent and the fractal dimension of the adsorption sites for quasi-monolayer adsorption, and of the adsorbed aggregate for a simple case of multilayer adsorption. We further check whether the Freundlich adsorption mechanism may contribute to anomalous diffusion in the transport through porous materials. PMID- 27414953 TI - The effects of paternal depression on child and adolescent outcomes: A systematic review. AB - BACKGROUND: Paternal depression has been associated with suboptimal developmental outcomes in offspring. We sought to systematically review the research evidence from prospective studies for an association between paternal depression and child adolescent emotional and behavioral outcomes. We also reviewed potential mediators of this association and sources of methodological bias. METHODS: A systematic review was conducted using the following databases: Medline, EMBASE, PsycINFO and Google Scholar. Reference lists of the included papers were also searched. RESULTS: Twenty-one studies were included in the review. Findings suggested that paternal depression does negatively impact upon offspring development. This impact is observable when paternal depression is present in the antenatal and postnatal stages and during offspring adolescence. The strength of this association is strongly reliant upon a number of contextual mediators, namely; paternal negative expressiveness, hostility and involvement and marital conflict. A quality assessment rating showed the studies were relatively strong methodologically. LIMITATIONS: Heterogeneity regarding method of assessment and the magnitude and timing of exposure hinder attempts to make strong conclusions regarding the trajectory of paternal depression and its effects on child and adolescent outcomes. CONCLUSIONS: Paternal mental health screening during pregnancy is necessary in order to identify and prevent depression negatively impacting offspring functioning. Including both parents in this process should encourage the alleviation of the environmental mediators which dominate the negative association outlined within the review. Research examining gene environment interaction is necessary to uncover more accurate details regarding paternal depression and subsequent offspring vulnerability. PMID- 27414952 TI - The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies. AB - Inflammatory bowel diseases are an increasing phenomenon in western countries and in growing populations. The physiopathology of these conditions is linked to intestinal stem cells homeostasis and regenerative potential in a chronic inflammatory microenvironment. Patients with IBD present an increased risk of developing colorectal cancer (CRC), or colitis associated cancer (CAC). Conventional treatment for IBD target the inflammatory process (and include anti inflammatory and immunosuppressive drugs) with biological agents emerging as a therapeutic approach for non-responders to traditional therapy. Conventional treatment provides scarce results and present severe complications. The intestinal environment may host incoming stem cells, able to engraft in the epithelial damaged sites and differentiate. Therefore, stem cell therapies represent an emerging alternative in inflammatory bowel diseases, with current investigations on the use of haematopoietic and mesenchymal stem cells, in particular adipose stem cells, apparently fundamental as regenerators and as immune-modulators. Here, we discuss stem cells in intestinal homeostasis and as therapeutic agents for the treatment of inflammatory bowel diseases. PMID- 27414955 TI - TfNHNHBoc as a Trifluoromethylating Agent for Vicinal Difunctionalization of Terminal Alkenes. AB - An unprecedented application of trifluoromethanesulfonyl hydrazides as trifluoromethylating agents has been demonstrated in two vicinal difunctionalization reactions of terminal alkenes: the copper-catalyzed three component vicinal chlorotrifluoromethylation of arylakenes with TfNHNHBoc and NaCl and the tandem trifluoromethylation/cyclization of N-arylacrylamides with TfNHNHBoc. The reactions proceeded in the presence of inexpensive oxidants under mild conditions and provided a range of structurally diverse trifluoromethyl containing compounds with high regioselectivity. PMID- 27414956 TI - Memory and language improvements following cognitive control training. AB - Cognitive control refers to adjusting thoughts and actions when confronted with conflict during information processing. We tested whether this ability is causally linked to performance on certain language and memory tasks by using cognitive control training to systematically modulate people's ability to resolve information-conflict across domains. Different groups of subjects trained on 1 of 3 minimally different versions of an n-back task: n-back-with-lures (High Conflict), n-back-without-lures (Low-Conflict), or 3-back-without-lures (3-Back). Subjects completed a battery of recognition memory and language processing tasks that comprised both high- and low-conflict conditions before and after training. We compared the transfer profiles of (a) the High- versus Low-Conflict groups to test how conflict resolution training contributes to transfer effects, and (b) the 3-Back versus Low-Conflict groups to test for differences not involving cognitive control. High-Conflict training-but not Low-Conflict training-produced discernable benefits on several untrained transfer tasks, but only under selective conditions requiring cognitive control. This suggests that the conflict focused intervention influenced functioning on ostensibly different outcome measures across memory and language domains. 3-Back training resulted in occasional improvements on the outcome measures, but these were not selective for conditions involving conflict resolution. We conclude that domain-general cognitive control mechanisms are plastic, at least temporarily, and may play a causal role in linguistic and nonlinguistic performance. (PsycINFO Database Record PMID- 27414958 TI - Introduction. PMID- 27414954 TI - Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy. AB - BACKGROUND: Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. METHODS: 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion. RESULTS: At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-beta than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-beta levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-beta changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-alpha and CRP levels were found in relation to melancholia or response to ECT. LIMITATIONS: As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. CONCLUSIONS: Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-beta, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation. PMID- 27414957 TI - Distinct ERP signatures of word frequency, phrase frequency, and prototypicality in speech production. AB - Recent studies have documented frequency effects for word n-grams, independently of word unigram frequency. Further studies have revealed constructional prototype effects, both at the word level as well as for phrases. The present speech production study investigates the time course of these effects for the production of prepositional phrases in English, using event related potentials (ERPs). For word frequency, oscillations in the theta range emerged. By contrast, phrase frequency showed a persistent effect over time. Furthermore, independent effects with different temporal and topographical signatures characterized phrasal prototypicality. In a simulation study we demonstrate that naive discrimination learning provides an alternative account of the data that is as least as powerful as a standard lexical predictor analysis. The implications of the current findings for models of language processing are discussed. (PsycINFO Database Record PMID- 27414959 TI - Cme credit quiz. PMID- 27414960 TI - Cme credit answer sheet. PMID- 27414961 TI - Index to Advertisers. PMID- 27414962 TI - Using the refined ICF Linking Rules to compare the content of existing instruments and assessments: a systematic review and exemplary analysis of instruments measuring participation. AB - BACKGROUND: Existing instruments measuring participation may vary with respect to various aspects. This study aimed to examine the comparability of existing instruments measuring participation based on the International Classification of Functioning, Disability and Health (ICF) by considering aspects of content, the perspective adopted and the categorization of response options. METHODS: A systematic literature review was conducted to identify instruments that have been commonly used to measure participation. Concepts of identified instruments were then linked to the ICF following the refined ICF Linking Rules. Aspects of content, perspective adopted and categorization of response options were documented. RESULTS: Out of 315 instruments identified in the full-text screening, 41 instruments were included. Concepts of six instruments were linked entirely to the ICF component Activities and Participation; of 10 instruments still 80% of their concepts. A descriptive perspective was adopted in most items across instruments (75%), mostly in combination with an intensity rating. An appraisal perspective was found in 18% and questions from a need or dependency perspective were least frequent (7%). CONCLUSION: Accounting for aspects of content, perspective and categorization of responses in the linking of instruments to the ICF provides detailed information for the comparison of instruments and guidance on narrowing down the choices of suitable instruments from a content point of view. Implications for Rehabilitation For clinicians and researchers who need to identify a specific instrument for a given purpose, the findings of this review can serve as a screening tool for instruments measuring participation in terms of the following: * Their content covered based on the ICF. * The perspective adopted in the instrument (e.g., descriptive, need/dependency or appraisal). * The categorization of their response options (e.g., intensity or frequency). PMID- 27414964 TI - Long-term Consequences of Early Undernourishment on the Activation of Brain Serotonin Synthesis in the Rat: Effect of Nutritional Recovery during the Period of Nursing. AB - In the present study we report that the undernourished rats during fetal life submitted to a neonatal recovery regime had a return to normal metabolic and physical growth conditions during the nursing period, and that their food consumption was more than controls, from weaning until adult age. However, in spite of the metabolic and physical recovery of the gestational undernourished rats, the activity of brain tryptophan-5-hydroxylase (TrpOH) remained elevated accompanied by an increase in the concentration of the neurotransmitter, serotonin (5-HT). Besides, the current observation confirms and extends to previous results, that an increase in brain 5-HT content, in L-tryptophan (L-Trp) concentration and in the activity of TrpOH, in undernourished rats occurs not only during gestation and lactation periods, but it lasts until adulthood. The increase in the activity of TrpOH observed during the fetal stage and continuing to postnatal life in undernourished rats seems to be secondary to an increased transport of plasma L-Trp to their brain. These findings suggest the hypothesis that the mechanism of accelerated synthesis of brain 5-HT in the adult nutritionally recovered animals, may not depended on the increased availability of free plasma L-Trp observed in the undernourished rats, but might be due to a specific change in the TrpOH structure, supported by previous results showing different kinetic and phosphorylating properties. Our observations also suggest that the increased food intake in the recovered animals imply changes in feeding behavior possibly related to the altered serotonin brain neurotransmission. PMID- 27414963 TI - 11% Efficient Ternary Organic Solar Cells with High Composition Tolerance via Integrated Near-IR Sensitization and Interface Engineering. AB - Highly efficient electron extraction is achieved by using a photoconductive cathode interlayer in inverted ternary organic solar cells (OSCs) where a near-IR absorbing porphyrin molecule is used as the sensitizer. The OSCs show improved device performance when the ratio of the two donors varies in a large region and a maximum power conversion efficiency up to 11.03% is demonstrated. PMID- 27414965 TI - Eating Behavior is Associated to Sympathetic Activation Induced by ICV Injection of Prostaglandin E1 in the Rat. AB - This experiment tests the effect of intracerebro-ventricular (icv) injection of prostaglandin E1 (PGE1) on. (1) food intake, (2) sympathetic activity and body temperature. The firing rate of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures (TIBAT and TC) were monitored in male Sprague-Dawley rats before and for 90 min after food presentation. An icv injection of PGE1 (500 ng) or saline was made immediately before food presentation. The amount of food ingested was also measured. The same procedure was carried out in control rats without food presentation. The results show that PGE1 raises the sympathetic firing rate, TIBAT and TC and it causes a decrease in food intake. These findings suggest that the food intake is associated to the sympathetic activity in the PGE1-hyperthermia. PMID- 27414966 TI - Severe Gestational Hypothyroidism Increases BBB Nutrient Transport in the Offspring. AB - Brain growth spurt and development is highly influenced by thyroid hormones. We reported earlier that chronic maternal potassium thiocyanate feeding (induced moderate hypothyroidism) resulted in reversible decrease in Blood-Brain Barrier (BBB) glucose transport in the offspring. To assess whether severe hypothyroidism as often seen in endemic areas would have greater effect, we have now determined the thyroid status and BBB nutrient transport in the pups born to dams made severely hypothyroid by feeding 6-n-propyl thiouracil (PTU), the potent antithyroid compound. The pups of PTU fed dams had lower birth weights (P < 0.001) than controls. Their weanling body weight and brain weight were also significantly lower. They were very severely hypothyroid (serum T4 < 0.7 MUg/d1 and T3 < 0.5 ng/ml) and surprisingly there was a significant increase in the BBB transport of all three nutrients tested (leucine, tyrosine and 2-deoxy-D glucose). The increased BBB nutrient transport however does not appear to be due to opening/breakdown of BBB as evident from the lack of extravasation of Evans blue injected into the carotid artery. Interestingly, T3 supplementation to the dams and offspring, could mitigate the changes not only in BBB nutrient transport but also their body and brain weights at weanling. PMID- 27414967 TI - Probable Basis of Altered BBB Nutrient Transport in the Offspring of Severely Hypothyroid Dams. AB - Recently we observed increased transport of nutrients across the blood-brain barrier (BBB) in the offspring born to mothers fed a potent antithyroid compound, 6-n-propyl-2-thiouracil (PTU) during gestation and lactation. The probable basis of this altered BBB nutrient transport in these pups has now been assessed by determining the kinetics of the transport of 2-deoxy-D-glucose across the BBB in situ, the fluidity of the isolated brain microvessel plasma membranes and their fatty acid profile. The maximal transport capacity (Tmax app) of the BBB transport system was markedly increased in the pups of PTU fed dams compared to controls. The fluidity of the brain microvessel endothelial cell plasma membrane (BMVPM) was increased significantly (P < 0.05) and this appeared to be due to an increase in unsaturation index (P < 0.001)/polyunsaturated fatty acid content of BMVPMs (P < 0.005). The results suggest that the increased BBB nutrient transport in the pups of severely hypothyroid dams could be due to changes in membrane microenvironment, altering the kinetics of BBB transport system and/or exposure of latent transporters. PMID- 27414968 TI - Effects of Snack Intake on Appetite, Affect and Attention. AB - To test the hypothesis that snacks eaten in the afternoon influence appetite, affect and performance on a simple attention task, an experiment was conducted using a dose-response design. Thirty male volunteers attended the laboratory on five occasions to consume a standard lunch and then to eat a snack three hours later varying in size and carbohydrate/fat content. The effects of consuming four snacks of increasing energy content (124, 274, 424 and 724 kcal) on ratings of hunger, fullness, appetite and mood as well as reaction time and accuracy in a perceptual discrimination task were investigated. Although appetite variables were responsive to the dose-response manipulation, mood and performance were only weakly influenced by snack intake. Lunch produced a greater impact on mood than snack consumption. The larger snacks decreased fatigue and only marginally improved reaction time. It is concluded that when level of deprivation, sensory, hedonic and expectancy effects were controlled, snack intake produced relatively subtle effects on mood and attention. PMID- 27414969 TI - Copper-deficient Rats have Altered Plasma Dihydroxyphenylacetic acid and Spleen Catecholamine Levels. AB - Perinatal copper (Cu) deficiency was produced in month old female and male Sprague Dawley rats by beginning low Cu treatment at day 7 of gestation and continuing throughout lactation. Offspring were maintained on the treatment of their dams from postnatal day 21-30. Compared to Cu-adequate rats Cu-deficient rats of both genders were smaller, had increased heart/body weight and lower liver copper levels. Plasma and spleen catecholamine levels were measured by HPLC. Plasma dihydroxyphenylacetic acid (DOPAC) levels, a dopamine (DA) metabolite, were higher in Cu-deficient females and males. Spleen norepinephrine (NE) was lower in Cu-deficient males and spleen DA was higher in both females and males compared to controls. Postnatal Cu deficiency was also studied in 54-day old male Holtzman rats after 5 weeks of dietary treatment. Cu-deficient males had higher plasma DOPAC, lower spleen NE, higher spleen DA, and higher spleen dihydroxyphenylglycol (DHPG) content, an NE metabolite. Plasma DOPAC data are consistent with higher tissue levels of DA and limiting dopamine-beta monooxygenase activity (DBM) in Cu-deficient rats. Lower tissue NE might also be due to lower DBM activity. Plasma DHPG, which was not altered, and spleen DHPG, which was elevated by Cu deficiency, do not support lower NE synthesis in Cu deficiency. Plasma DOPAC might be useful to assess nutritional Cu status. PMID- 27414970 TI - Differential Effects of Prenatal Protein Malnutrition and Prenatal Cocaine on Radial Arm Maze Performance in Adult Male Rats. AB - The effects of prenatal cocaine and protein malnutrition were examined on acquisition of the radial arm maze in adult male Sprague-Dawley rats whose mothers were provided with a 6% casein, a 25% casein or a standard chow diet and cocaine (30mg/kg) or saline injections beginning 5 weeks prior to mating and continuing to parturition. Rats were tested using an 8-arm radial maze with 4 baited arms and were required to collect all 4 food pellets within 5 min to complete a trial. Subjects were tested for 1 trial/day until they met criterion for successful acquisition of the task. Criterion was attained when the rat collected 3 out of the 4 food pellets within their first 4 arm entries within a trial (while still completing the trial) with this level of performance being maintained for 3 consecutive trials. The results showed dissociation between the effects of prenatal protein malnutrition and prenatal cocaine. Prenatally protein malnourished adult male rats required a greater number of trials to criterion, made more reference memory (but not working memory) errors, and required a longer time to complete each trial when compared with control males. However, rats with prenatal cocaine exposure showed no significant impairments in the radial arm maze. These results contrast with our previous findings using the Morris maze task in which adult male subjects exhibited impaired acquisition following prenatal cocaine while there were no effects following prenatal protein malnutrition. Thus, the radial arm maze and water maze procedures appear to engage different processes that are differentially sensitive to the prenatal insults. PMID- 27414971 TI - Caffeine Withdrawal and Headaches. AB - Previous research has shown that cessation of caffeine consumption may be associated with a distinct withdrawal syndrome, typified by an increase in headaches. Recent research suggests that low to moderate consumers of caffeine may report an increase in headaches if they perceive caffeine to have been withdrawn regardless of whether it has been or not. The present study provides additional support for the role of subjective perceptions in the caffeine withdrawal syndrome. Forty-three low caffeine consumers recorded the incidence of headaches when drinking caffeinated or decaffeinated beverages. When caffeine was withdrawn the incidence of headaches increased but this effect was only significant in those individuals who could discriminate whether they were consuming caffeinated or decaffeinated beverages. This result suggests a major role of subjective perceptions and expectancies in the caffeine withdrawal syndrome, a view that contrasts with the notion that a significant proportion of caffeine consumers are physically dependent upon caffeine. PMID- 27414972 TI - Genetic Causes of Recurrent Pregnancy Loss. AB - Pregnancy loss is one of the most common obstetric complications, affecting over 30% of conceptions. A considerable proportion of losses are due to genetic abnormalities. Indeed, over 50% of early pregnancy losses have been associated with chromosomal abnormalities. Most are due to de novo nondisjunctional events but balanced parental translocations are responsible for a small but important percentage of genetic abnormalities in couples with recurrent pregnancy loss. In the past, assessment of genetic abnormalities was limited to karyotype performed on placental or fetal tissue. However, advances in molecular genetic technology now provide rich genetic information about additional genetic causes of and risk factors for pregnancy loss. In addition, the use of preimplantation genetic testing in couples undergoing in vitro fertilization has the potential to decrease the risk of pregnancy loss from genetic abnormalities. To date, efficacy is uncertain but considerable potential remains. This chapter will review what is known about genetic causes of recurrent pregnancy loss with a focus on novel causes and potential treatments. Remaining knowledge gaps will be highlighted. PMID- 27414973 TI - Prospective Randomized Trial Investigating the Influence of Pharmaceutical Care on the Intra-Individual Variability of Tacrolimus Concentrations Early After Kidney Transplant. AB - BACKGROUND: This study evaluated the influence of pharmaceutical care (PhC) in the intra-individual variability of dose-corrected whole blood tacrolimus (TAC) trough concentrations, adherence to immunosuppressive therapy and clinical outcomes. METHODS: We randomized 128 kidney transplant recipients to receive PhC consisted of predefined instructions provided by a pharmacist (PhC group, n = 64) or standard nurse staff instructions (control group, n = 64) from day 3 to day 90 after kidney transplantation. The study was powered to detect at least 50% reduction in the coefficient of variation (%CV), calculated from 6 dose-corrected whole blood TAC trough concentrations, in the PhC group. Patient adherence was evaluated using Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) questionnaire. RESULTS: There was no difference in the %CV comparing PhC and control group (31.4% +/- 12.3% versus 32.5% +/- 16.1%, P = 0.673). There were no differences in the proportion of patients showing TAC concentrations within predefined target concentrations in each study visit. There was no difference in the proportion of nonadherent patients at day 28 (17% versus 26%, P = 0.135) and day 90 (27% versus 25%, P = 0.457) based on BAASIS questionnaire answers, respectively. There were no differences in clinical outcomes. CONCLUSIONS: Universal PhC in addition to standard nurse staff instruction was not associated with reduced intra-individual variability of dose corrected whole blood TAC trough concentrations or improved adherence. PMID- 27414974 TI - The Impact of Pharmacokinetic Interactions With Eslicarbazepine Acetate Versus Oxcarbazepine and Carbamazepine in Clinical Practice. AB - BACKGROUND: Eslicarbazepine acetate (ESL) is a new anti-epileptic drug (AED) chemically related to oxcarbazepine (OXC) and carbamazepine (CBZ) and is increasingly used in clinical practice. The purpose of the study was to investigate 2-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ. METHODS: Anonymous data regarding age, gender, use of AEDs, daily doses and serum concentration measurements of ESL, OXC, CBZ and lamotrigine (LTG) and other AEDs were retrieved from 2 therapeutic drug monitoring (TDM) databases in Norway. Drugs were categorized according to their known potential for interactions. Concentration/dose (C/D) ratios were calculated. RESULTS: Data from 1100 patients were available. The C/D ratios of ESL and OXC were unchanged in combination with enzyme-inducing AEDs or valproate (VPA). The C/D ratio of CBZ decreased by 40% and 22% in combination with other enzyme-inducing AEDs or VPA, respectively, pointing to an increased clearance. ESL demonstrated no significant enzyme-inducing effect on LTG metabolism although there was a 20% and 34% decrease in the C/D ratio of LTG in combination with OXC and CBZ, respectively. CONCLUSIONS: Possible pharmacokinetic interactions have been studied for ESL as compared to OXC and CBZ. The pharmacokinetics of ESL is not affected by enzyme-inducing AEDs or VPA and does not affect the metabolism of LTG in contrast to OXC and CBZ. The study demonstrates the value of using TDM databases to explore the potential for pharmacokinetic interactions of new AEDs. PMID- 27414975 TI - Ultrafast Online SPE-MS/MS Method for Quantification of 3 Tyrosine Kinase Inhibitors in Human Plasma. AB - BACKGROUND: With an increasing number of cancer patients receiving tyrosine kinase inhibitors (TKIs), therapeutic drug monitoring of these molecules is becoming more widespread today. It is mainly based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) methods with typical run times of several minutes. In an online solid phase extraction-MS/MS (SPE-MS/MS) system, the chromatography column is replaced with a reusable solid phase extraction (SPE) cartridge and the analysis time is shortened to less than half a minute. The aim of this study was to develop such a method and test the performance of this high-throughput system in the analysis of imatinib (IMA), nilotinib (NIL), and lapatinib (LAP) in human plasma. METHODS: Samples were prepared by simple protein precipitation with methanol containing deuterated internal standards. After centrifugation, the supernatant was diluted 10 fold with a mixture of methanol and water (1:1). A C4 cartridge was used for SPE and the analytes were eluted by acetonitrile. All the analytes were measured within a wide calibration range (50-5000 ng/mL for nilotinib and imatinib, 100-10,000 ng/mL for lapatinib). The method was compared with the LC-MS/MS method by the analysis of 176 clinical samples. RESULTS: Intraday and interday inaccuracies within 15% and a coefficient of variation less than 15% were achieved for all the TKIs that were measured. Even though the matrix effects were higher in comparison with LC-MS/MS methods, their effect on the performance of the method was eliminated by the usage of deuterated internal standards. The total run time of the new method was 29 seconds for one analysis and the results were fully comparable with LC-MS/MS. CONCLUSIONS: Routine clinical practice requiring high-throughput methods for therapeutic drug monitoring of TKIs may benefit from the online SPE-MS/MS method that provides fast, low-cost analysis, and results that are comparable with conventional methods. PMID- 27414976 TI - Platelet function testing as a biomarker for efficacy of antiplatelet drugs. AB - Despite the overwhelming evidence in support of the efficacy of dual antiplatelet therapy with aspirin and clopidogrel, it is also obvious that not all patients benefit from these drugs to the same extent. This interindividual variability in platelet responses may underlie clinical differences in drug efficacy, with potential for optimization of antiplatelet therapy to prevent ischemic events without excessively increasing bleeding risk. This review presents the current evidence regarding platelet function testing for monitoring of antiplatelet therapy, with emphasis on the prognostic value of platelet function testing to predict ischemic and bleeding events. The potential of platelet function testing to provide personalized antiplatelet therapy is also discussed, with an outlook toward the future of platelet function testing in high-risk individuals. PMID- 27414977 TI - Dynamics of Electron Injection in SnO2/TiO2 Core/Shell Electrodes for Water Splitting Dye-Sensitized Photoelectrochemical Cells. AB - Water-splitting dye-sensitized photoelectrochemical cells (WS-DSPECs) rely on photoinduced charge separation at a dye/semiconductor interface to supply electrons and holes for water splitting. To improve the efficiency of charge separation and reduce charge recombination in these devices, it is possible to use core/shell structures in which photoinduced electron transfer occurs stepwise through a series of progressively more positive acceptor states. Here, we use steady-state emission studies and time-resolved terahertz spectroscopy to follow the dynamics of electron injection from a photoexcited ruthenium polypyridyl dye as a function of the TiO2 shell thickness on SnO2 nanoparticles. Electron injection proceeds directly into the SnO2 core when the thickness of the TiO2 shell is less than 5 A. For thicker shells, electrons are injected into the TiO2 shell and trapped, and are then released into the SnO2 core on a time scale of hundreds of picoseconds. As the TiO2 shell increases in thickness, the probability of electron trapping in nonmobile states within the shell increases. Conduction band electrons in the TiO2 shell and the SnO2 core can be differentiated on the basis of their mobility. These observations help explain the observation of an optimum shell thickness for core/shell water-splitting electrodes. PMID- 27414978 TI - Therapy-related myelodysplastic syndrome following primary breast cancer. AB - BACKGROUND: Therapy-related myelodysplastic syndrome (t-MDS) is a serious clinical disease occurring after breast cancer treatment. METHODS: A cohort of 11,684 invasive breast cancer (BC) patients from 1990-2014 were followed for incidence of t-MDS through institutional and the Surveillance, Epidemiology and End Results (SEER) Program registries. t-MDS cases were identified using ICD-O SEER registry codes, pathology and chart reports. Treatment, cytogenetics, and time from BC diagnosis to t-MDS and t-MDS diagnosis to last follow up or death were obtained. Incidence rate ratios were calculated using SEER national incidence rates for comparison. RESULTS: 27 cases of t-MDS post BC treatment were confirmed. 96% of cases were breast cancer stage I-II at diagnosis. All patients had received radiation treatment and 59% received adjuvant chemotherapy. Two patients were alive with no evidence of disease after treatment with stem cell transplantation (age 33 and 46). t-MDS incidence was 30 times the expected population rate among patients <55 years (RR 31.8, 95% CI 15.0, 60.8) with shorter time from t-MDS diagnosis to death (median survival time: <55: 8 months, 55-74: 26 months, 75+: 23 months). CONCLUSION: We found elevated t-MDS risk especially among younger BC patients with stem cell transplantation the only observed curative treatment. PMID- 27414979 TI - Erratum: Reliability Criteria for Liver Stiffness Measurements with Real-Time 2D Shear Wave Elastography in Different Clinical Scenarios of Chronic Liver Disease. PMID- 27414981 TI - Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice. AB - Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-alpha and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID- 27414980 TI - Role of Contrast-Enhanced Ultrasound (CEUS) in Paediatric Practice: An EFSUMB Position Statement. AB - The use of contrast-enhanced ultrasound (CEUS) in adults is well established in many different areas, with a number of current applications deemed "off-label", but the use supported by clinical experience and evidence. Paediatric CEUS is also an "off-label" application until recently with approval specifically for assessment of focal liver lesions. Nevertheless there is mounting evidence of the usefulness of CEUS in children in many areas, primarily as an imaging technique that reduces exposure to radiation, iodinated contrast medium and the "patient friendly" circumstances of ultrasonography. This position statement of the European Federation of Societies in Ultrasound and Medicine (EFSUMB) assesses the current status of CEUS applications in children and makes suggestions for further development of this technique. PMID- 27414982 TI - Simultaneous determination and stability studies of linezolid, meropenem and vancomycin in bacterial growth medium by high-performance liquid chromatography. AB - For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models. To separate sample matrix components, the final method comprised the pretreatment of 100MUL sample with 400MUL methanol, the evaporation of supernatant and its reconstitution in water. A low sample volume of 2MUL processed sample was injected onto an Accucore C-18 column (2.6MUm, 100*2.1mm) coupled to a Dionex Ultimate 3000 HPLC+ system. UV detection at 251, 240 and 302nm allowed quantification limits of 0.5, 2 and 0.5MUg/mL for LZD, VAN and MER, respectively. The assay was successfully validated according to the relevant EMA guideline. The rapid method (14min) was successfully applied to quantify significant degradation of LZD, VAN and MER in in vitro infection models: LZD was stable, VAN degraded to 90.6% and MER to 62.9% within 24h compared to t=0 in CaMHB at 37 degrees C, which should be considered when deriving PK/PD relationships in in vitro infection models. Inclusion of further antibiotics into the flexible gradient-based HPLC assay seems promising. PMID- 27414983 TI - New Concept of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma and Its Impact on the Bethesda System for Reporting Thyroid Cytopathology: A Single-Institute Experience. AB - BACKGROUND: The encapsulated follicular variant (EFV) of papillary thyroid carcinoma (PTC) is the most discussed entity in thyroid pathology. Recently, the question of whether or not EFV-PTC is a malignant entity has been the subject of renewed discussion in the light of recent molecular and clinical studies. The aim of this study was to analyze the malignancy ratios of each category of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) if EFV-PTC is no longer considered as a malignant entity. MATERIALS AND METHODS: Data on thyroid fine-needle aspirations (n = 1,886) with surgical follow-up between 1999 and 2014 were studied. EFV-PTC cases constituted 27% (94/343) of the malignant cases. RESULTS: Malignancy ratios were determined as nondiagnostic, benign, atypia/follicular lesion of undetermined significance, suspicious for follicular neoplasm/follicular neoplasm, suspicious for malignancy, and malignant categories of the TBSRTC in 13, 7, 45, 30, 72 and 98%, respectively. If EFV-PTC was not regarded as malignant, malignancy ratios would decrease to 6.5, 6, 30, 10, 48, and 87% for each category in the same order. CONCLUSIONS: The current study showed that the most significant decrease in relative malignancy ratios was seen in the suspicious for follicular neoplasm/follicular neoplasm category (66% relative decrease), but all categories represented a considerable decrease. PMID- 27414984 TI - Genetic risk factors for venous thrombosis in women using combined oral contraceptives: update of the PILGRIM study. AB - Identifying women at risk of venous thrombosis (VT) under combined oral contraceptives (COC) is a major public health issue. The aim of this study was to investigate in COC users the impact on disease of genetic polymorphisms recently identified to associate with VT risk in the general population. Nine polymorphisms located on KNG1, F11, F5, F2, PROCR, FGG, TSPAN and SLC44A2 genes were genotyped in a sample of 766 patients and 464 controls as part of the PILGRIM (PILl Genetic Risk Monitoring) study. Cases were women who experienced an episode of documented VT during COC use, while controls were women with no history of VT using COC at the time of inclusion. Among the studied polymorphisms, only F11 rs2289252 was significantly associated with VT. The F11 rs2289252-A allele was associated with a 1.6-fold increased risk of VT (p < 0.0001). Besides, the combination of the rs2289252-A allele with non-O blood group, present in 52% of the cohort, was associated with an odds ratio of 4.00 (2.49-6.47; p < 10-4 ). The consideration of this genetic risk factor could help to better assess the risk of VT in COC users. PMID- 27414985 TI - Insights on different analysis techniques in the monothermal and bithermal caloric test - which parameter should we use to quantify vestibular function? AB - OBJECTIVE: To investigate the use of maximum slow component velocity (MSCV) and time-constant duration (TCd) of elicited nystagmus in quantifying the caloric response and to assess the efficacy of these parameters in the monothermal screening test. DESIGN: Retrospective analysis of caloric results obtained from 150 patients. Bithermal unilateral weakness (UW), directional preponderance (DP), monothermal caloric asymmetry (MCA) based on warm or cool irrigations only, were calculated using both MSCV and TCd. STUDY SAMPLE: 66 males and 84 females, aged 16-88 years (MU = 50, sigma = 17), who underwent vestibular assessment. RESULTS: The correlation-coefficient between bithermal caloric unilateral weaknesses calculated using either MSCV or TCd is 0.155 (p < 0.01). Using MSCV and setting significant MCA at 10%, the sensitivity and specificity were respectively 100% and 34% for monothermal warm and 82% and 53% for monothermal cool tests. Using TCd and setting significant MCA at 5%, the sensitivity and specificity were respectively 90% and 77% for monothermal warm and 100% and 74% for monothermal cool tests. CONCLUSIONS: In the monothermal warm caloric test, MSCV can be used more reliably than monothermal cool to predict normal bithermal caloric response. The reverse is true if using TCd. Unilateral-weakness calculated using TCd and MSCV were poorly correlated and therefore likely to be demonstrating different aspects of vestibular function. PMID- 27414986 TI - Effects of trans-2-hexenal on reproduction, growth and behaviour and efficacy against the pinewood nematode, Bursaphelenchus xylophilus. AB - BACKGROUND: Bursaphelenchus xylophilus is a serious quarantined pest that causes severe damage and major economic losses to pine forests. Because of the adverse effects of some traditional nematicides on humans and the environment, the search for new plant toxicants against these nematodes has intensified. Nematicidal activity of trans-2-hexenal, which is a six-carbon aldehyde present in many plants, was tested against the nematode. RESULTS: trans-2-Hexenal showed significant efficacy against B. xylophilus in a dose range of 349.5-699 g m-3 by fumigation of pinewood logs. Additionally, it had significant nematicidal activity against different life stages of B. xylophilus in an in vitro test, with second-stage larvae (L2s) being the most sensitive, with an LC50 value of 9.87 ug mL-1 at 48 h. Egg hatch was also significantly inhibited. Further studies revealed that trans-2-hexenal inhibited the reproductive activity of B. xylophilus, with negative effects on reproduction rate and egg numbers. Moreover, trans-2-hexenal reduced the body length of B. xylophilus. Respiratory rate and thrashing behaviour of B. xylophilus also decreased following treatment with this compound. CONCLUSION: trans-2-Hexenal had significant nematicidal activity against B. xylophilus, providing a basis for elucidation of the mode of action of trans-2-hexenal against plant-parasitic nematodes in future studies. (c) 2016 Society of Chemical Industry. PMID- 27414987 TI - Impact of ASPECTS on computed tomography angiography source images on outcome after thrombolysis or endovascular therapy in large vessel occlusions. AB - BACKGROUND AND PURPOSE: Endovascular therapy (ET) is superior to intravenous thrombolysis (IVT) in selected patients with anterior circulation large vessel occlusions. However, it is unclear if this positive effect also applies to patients with extensive early ischaemic changes. The aim of this study was to analyze the impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on the CT angiography source images (SI) on outcome after ET or IVT. METHODS: Using our prospectively obtained stroke database and the admission SI ASPECTS divided into three groups (0-5, 6-7 and 8-10), primarily the rates of good outcome [modified Rankin Scale (mRS) <=2 at discharge] after either ET (n = 255) or IVT (n = 479) were compared. RESULTS: A favorable SI-ASPECTS (8-10) was present in 501 patients, 132 patients had a moderately favorable SI-ASPECTS (6-7) and 101 patients had an unfavorable SI-ASPECTS (0-5). Irrespective of the treatment modality, no patient with an unfavorable SI-ASPECTS had a good outcome and 38% died during hospital stay. Whilst significantly more patients with a favorable SI-ASPECTS had a good outcome after ET than after IVT (51% vs. 35%, P < 0.01), there was only a non-significant trend towards a good outcome after ET than after IVT in patients with a moderately favorable ASPECTS (25% vs. 14%, P = 0.1). CONCLUSION: Patients with extensive early ischaemic changes on CT scans (SI ASPECTS <=5) might not profit from ET. The impact of ET on outcome in patients with moderately favorable SI-ASPECTS should be addressed in further trials. PMID- 27414989 TI - Interaction of Boron-Nitrogen Doped Benzene Isomers with Water. AB - The interaction of 1,2-dihydro-1,2-, 1,3-dihydro-1,3- and 1,4-dihydro-1,4 azaborine isomers with one and two water molecules has been studied using a variety of supermolecular (Moller-Plesset = MP, and coupled cluster = CC) as well as perturbational (symmetry-adapted perturbation theory = SAPT) electron correlation methods in the complete basis-set limit. It has been found that the water molecule binds to azaborine isomers through O-H...pi, pi-H...O, and dihydrogen bonding linkages. The SAPT interaction energy decomposition shows that these complexes are mostly stabilized by dispersion followed closely by induction contributions. Pauli repulsion hinders water molecule to be polarized by azaborine in the O-H...pi type of complexes. According to the interacting-quantum atoms analysis, the structures with a primary binding of the O-H...pi type benefit from an additional stabilization factor resulting from the interaction of the oxygen and the second hydrogen atom of water, i.e., the one which does not point toward the ring, while the interaction of hydrogens from water with azaborines plays a destabilizing role for the pi-H...O type. The same method states that the intermolecular bindings between azaborines and the water molecule have a multicenter character with a small bond polarization, and they are classified as closed-shell (noncovalent) by quantum theory of atoms-in-molecules analysis at bond critical points. The complexes of azaborines with two water molecules tend to arrange in a circular fashion with a recognizable water dimer attached to the azaborine molecule. A comparison with the CCSD(T) benchmarks shows that the nonadditive contribution to the interaction energy of the trimers is negative and with a good accuracy can be accounted for by the MP2 method. A good agreement between Hartree-Fock (HF) and MP2 nonadditive energy, as well as the decomposition of HF nonadditive interaction energies divulge the importance of nonadditive induction energy in the trimers. The interaction energies for the azaborine with one water calculated with the SAPT(DFT), MP2, SCS-MP2, and MP2C methods are in satisfactory agreement with each other. Finally, it has been found that the population analysis from the electron localization function offers the most comprehensive explanation of the orientational preferences of the water molecule in the complex. PMID- 27414990 TI - Cell Surface Display Fungal Laccase as a Renewable Biocatalyst for Degradation of Persistent Micropollutants Bisphenol A and Sulfamethoxazole. AB - Fungal laccases have high activity in degrading various persistent organic pollutants. However, using enzymes in solution for water treatment has limitations of nonreusability, short enzyme lifetimes, and high cost of single use. In this study, we developed a new type of biocatalyst by immobilizing fungal laccase on the surface of yeast cells using synthetic biology techniques. The biocatalyst, referred to as surface display laccase (SDL), had an enzyme activity of 104 +/- 3 mU/g dry cell (with 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS)). The SDL retained over 90% of the initial enzyme activity after 25 days storage at room temperature, while, in contrast, activity of free laccase declined to 60% of its initial activity. The SDL could be reused with high stability as it retained 74% of initial activity after eight repeated batch reactions. Proof-of-concept evaluations of the effectiveness of SDL in treating contaminants of emerging concern were performed with bisphenol A and sulfamethoxazole. Results from contaminant degradation kinetics and the effects of redox mediator amendment provided insights into the factors affecting the efficacy of the SDL system. This study reports, for the first time, the development of a surface display enzyme biocatalyst as an effective and renewable alternative for treating recalcitrant organic micropollutants. PMID- 27414988 TI - Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond. AB - BECN1 (Beclin 1), a highly conserved eukaryotic protein, is a key regulator of autophagy, a cellular homeostasis pathway, and also participates in vacuolar protein sorting, endocytic trafficking, and apoptosis. BECN1 is important for embryonic development, the innate immune response, tumor suppression, and protection against neurodegenerative disorders, diabetes, and heart disease. BECN1 mediates autophagy as a core component of the class III phosphatidylinositol 3-kinase complexes. However, the exact mechanism by which it regulates the activity of these complexes, or mediates its other diverse functions is unclear. BECN1 interacts with several diverse protein partners, perhaps serving as a scaffold or interaction hub for autophagy. Based on extensive structural, biophysical and bioinformatics analyses, BECN1 consists of an intrinsically disordered region (IDR), which includes a BH3 homology domain (BH3D); a flexible helical domain (FHD); a coiled-coil domain (CCD); and a beta alpha-repeated autophagy-specific domain (BARAD). Each of these BECN1 domains mediates multiple diverse interactions that involve concomitant conformational changes. Thus, BECN1 conformational flexibility likely plays a key role in facilitating diverse protein interactions. Further, BECN1 conformation and interactions are also modulated by numerous post-translational modifications. A better structure-based understanding of the interplay between different BECN1 conformational and binding states, and the impact of post-translational modifications will be essential to elucidating the mechanism of its multiple biological roles. PMID- 27414992 TI - An innovative approach to digitally flip the classroom by using an online "graffiti wall" with a blog. PMID- 27414991 TI - "All the soarings of my mind begin in my blood:" central nervous system complication of Waldenstrom macroglobulinemia. PMID- 27414993 TI - Intra-Aortic Balloon Occlusion (IABO) may be useful for the management of secondary aortoduodenal fistula (SADF): A case report. AB - INTRODUCTION: Secondary aortoduodenal fistula (SADF) is a rare but life threatening complication after aortic reconstruction. Although a number of reports describing treatments for SADF have been published, the optimal management is unclear. A review of the literature suggested methods of reconstruction, control of bleeding, and reduction of infection in the management of SADF. The most important factor for acute intervention is controlling the bleeding from the fistula. We report one case treated using intra-aortic balloon occlusion (IABO) for SADF. PRESENTATION OF A CASE: We describe a case of secondary aortoduodenal fistula that occurred seven years following aortobifemoral reconstruction for abdominal aortic aneurysm. DISCUSSION: Early control of bleeding is essential for survival of the patient. Emergency laparotomy or endovascular stenting frequently have been chosen as interventions, although each approach has significant limitations. Emergency laparotomy for patients with hemodynamic instability may create excessive physiologic stress, and endovascular stenting may not be available at every surgical facility. The use of IABO for cases of intraperitoneal bleeding due to trauma has been previously described. IABO is relatively easy to implement, and enabled us to control the bleeding from the aorta more rapidly than other strategies. CONCLUSION: Based on a review of the literature and our own experience, IABO should be considered as one option for the management of SADF. PMID- 27414994 TI - Bone grafting with granular biomaterial in segmental maxillary osteotomy: A case report. AB - INTRODUCTION: Segmental maxillary osteotomy enables correction of anterior open bites. However, the outcome can be somewhat unstable, particularly if pseudarthrosis occurs. Bone grafts can be used to prevent this complication. Among the many biomaterials available for grafting, Bio-oss((r)) has been used successfully in a range of modalities, with studies to support several indications. This report describes a case of segmental maxillary osteotomy in which Bio-oss((r)) granules were used as bone grafts in the surgical gap. PRESENTATION OF CASE: A 24-year-old female presented with anterior open bite, Angle class III posterior occlusion, and Angle class II anterior occlusion. Virtual surgical planning of the procedure predicted a gap of approximately 5mm in the region of the osteotomy, which was bridged with Bio-oss((r)) granules. DISCUSSION: Although autogenous bone grafting is the gold standard due to its osteoconductive, osteoinductive, and osteogenic properties, it involves increased morbidity for the patient, unpredictable resorption rates, increased operative time, and risk of infection at the donor site. Use of the Bio-oss((r)) material can provide good bone stability, osteoconduction, and biocompatibility, while reducing operative time and surgical morbidity. CONCLUSION: This is the first report of bone grafting with a granular biomaterial in segmental maxillary osteotomy. Successful formation of new bone with density greater than that of the surrounding tissue was achieved, preventing pseudarthrosis and postoperative instability. PMID- 27414995 TI - Lumbar facet joint septic arthritis presenting atypically as acute abdomen - A case report and review of the literature. AB - INTRODUCTION: Septic arthritis of the lumbar facet joints is uncommon. The clinical presentation is unusual and patients usually presents with acute back pain or with signs and symptoms mimicking acute abdomen. PRESENTATION OF CASE: A 52year old man was admitted to the surgical ward with acute onset of abdominal pain and a provisional diagnosis of acute pyelonephritis. After the initial inconclusive investigations, magnetic resonance imaging was highly suggestive of lumbar facet joint septic arthritis. He was treated with intravenous antibiotics with complete resolution of infection. DISCUSSION: The diagnosis of septic arthritis of facet joint is becoming more common with MRI scans. The clinical signs and symptoms are usually difficult to differentiate from acute spondylodiscitis. The commonest organism isolated is Staphylococcus aureus. A prompt and early diagnosis and treatment help to eradicate infection and prevent complications. CONCLUSION: The atypical presentation of facet joint septic arthritis is one of the reasons why early diagnosis is elusive. Definitive diagnoses with MRI and bacterial culture as well as prolonged antibiotic therapy are recommended in this condition. PMID- 27414997 TI - The higher you climb: Dark side personality and job level. AB - The purpose of this study was to explore the idea that there are dark side personality differences in the profiles of people at different levels in organizations. This study replicates and extends existing leadership research by focusing on self-defeating behavioral tendencies. A Danish consultancy provided data on 264 adults based on assessment reports. This paper explored linear and quadratic relationships between personality and de facto job level. More senior managers scored high on Cluster B/Moving Against Others scales of Bold, Colorful and Imaginative, and low on Cautious and Dutiful. These Danish data are compared to data from Great Britain and New Zealand which show very similar findings. Practice should take into account that dark side personality traits associated with an assertive, sometimes hostile, interpersonal orientation, predict leadership level up to a point. PMID- 27414996 TI - A Large Capacity Cationic Metal-Organic Framework Nanocarrier for Physiological pH Responsive Drug Delivery. AB - A nanoscale cationic porous drug carrier ZJU-101 (ZJU = Zhejiang University), synthesized by the solvothermal method to get the crystal size of ~300 nm, was used to load diclofenac sodium, an anionic drug. This positively charged host materials showed a large loading capacity of diclofenac sodium (~0.546 g/g) through ion exchange and penetration procedures. The drug delivery in the inflamed tissues (pH = 5.4) exhibited a more effective release in comparison with that in the normal tissues (pH = 7.4), demonstrating a physiological pH responsive drug release. This discriminating drug release process was controlled by anion exchange between anions in phosphate buttered saline (PBS) and coordinated/free diclofenac anions. PMID- 27414998 TI - Global climate change driven by soot at the K-Pg boundary as the cause of the mass extinction. AB - The mass extinction of life 66 million years ago at the Cretaceous/Paleogene boundary, marked by the extinctions of dinosaurs and shallow marine organisms, is important because it led to the macroevolution of mammals and appearance of humans. The current hypothesis for the extinction is that an asteroid impact in present-day Mexico formed condensed aerosols in the stratosphere, which caused the cessation of photosynthesis and global near-freezing conditions. Here, we show that the stratospheric aerosols did not induce darkness that resulted in milder cooling than previously thought. We propose a new hypothesis that latitude dependent climate changes caused by massive stratospheric soot explain the known mortality and survival on land and in oceans at the Cretaceous/Paleogene boundary. The stratospheric soot was ejected from the oil-rich area by the asteroid impact and was spread globally. The soot aerosols caused sufficiently colder climates at mid-high latitudes and drought with milder cooling at low latitudes on land, in addition to causing limited cessation of photosynthesis in global oceans within a few months to two years after the impact, followed by surface-water cooling in global oceans in a few years. The rapid climate change induced terrestrial extinctions followed by marine extinctions over several years. PMID- 27415001 TI - Correction: mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile. AB - [This corrects the article DOI: 10.1371/journal.pone.0154564.]. PMID- 27414999 TI - Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development. AB - An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures. PMID- 27415000 TI - Assessment of Anti-TNF-alpha Activities in Keratinocytes Expressing Inducible TNF alpha: A Novel Tool for Anti-TNF-alpha Drug Screening. AB - Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine important in normal and pathological biological processes. Newly synthesized pro-TNF-alpha is expressed on the plasma membrane and cleaved to release soluble TNF-alpha protein: both are biologically active. Secreted TNF-alpha signals through TNF receptors and the membrane-bound TNF-alpha acts by cell contact-dependent signaling. Anti-TNF-alpha antibodies have been used effectively for treatment of chronic inflammation, however with adverse side effects. Thus, there is a need for new anti-TNF-alpha small molecule compounds. Anti-TNF-alpha activity assays involve treatment of keratinocytes with exogenous TNF-alpha before or after anti TNF-alpha incubation. However, this model fails to address the dual signaling of TNF-alpha. Here we describe a Doxycycline (Dox)-inducible TNF-alpha (HaCaT-TNF alpha) expression system in keratinocytes. Using this in-vitro model, we show cell inhibition and induced expression of pro-inflammatory cytokines and markers, including IL-1beta, IL-6, IL-8, NF-kappaB1, and KRT-16, similar to cells treated with exogenous TNF-alpha. Sufficient secreted TNF-alpha produced also activated IL-1beta and IL-8 expression in wt HaCaT cells. Importantly, stimulated expression of IL-1beta and IL-8 in HaCaT-TNF-alpha were blocked by Quercetin, a flavanol shown to possess anti-TNF-alpha activities. This novel in vitro cell model provides an efficient tool to investigate the dual signaling of TNF-alpha. Importantly, this model provides an effective, fast, and simple screening for compounds with anti-TNF-alpha activities for chronic inflammatory disease therapies. PMID- 27415002 TI - The Origin of Large-Bodied Shrimp that Dominate Modern Global Aquaculture. AB - Several shrimp species from the clade Penaeidae are farmed industrially for human consumption, and this farming has turned shrimp into the largest seafood commodity in the world. The species that are in demand for farming are an anomaly within their clade because they grow to much larger sizes than other members of Penaeidae. Here we trace the evolutionary history of the anomalous farmed shrimp using combined data phylogenetic analysis of living and fossil species. We show that exquisitely preserved fossils of ?Antrimpos speciosus from the Late Jurassic Solnhofen limestone belong to the same clade as the species that dominate modern farming, dating the origin of this clade to at least 145 mya. This finding contradicts a much younger Late Cretaceous age (ca. 95 mya) previously estimated for this clade using molecular clocks. The species in the farmed shrimp clade defy a widespread tendency, by reaching relatively large body sizes despite their warm water lifestyles. Small body sizes have been shown to be physiologically favored in warm aquatic environments because satisfying oxygen demands is difficult for large organisms breathing in warm water. Our analysis shows that large-bodied, farmed shrimp have more gills than their smaller-bodied shallow water relatives, suggesting that extra gills may have been key to the clade's ability to meet oxygen demands at a large size. Our combined data phylogenetic tree also suggests that, during penaeid evolution, the adoption of mangrove forests as habitats for young shrimp occurred multiple times independently. PMID- 27415003 TI - Performance Evaluation of NIPT in Detection of Chromosomal Copy Number Variants Using Low-Coverage Whole-Genome Sequencing of Plasma DNA. AB - OBJECTIVES: The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method. METHOD: A total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS) to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated. RESULTS: 33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively. CONCLUSION: Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs. PMID- 27415004 TI - Welfare at Multiple Scales: Importance of Zoo Elephant Population Welfare in a World of Declining Wild Populations. PMID- 27415005 TI - Functional Traits for Carbon Access in Macrophytes. AB - Understanding functional trait distributions among organisms can inform impacts on and responses to environmental change. In marine systems, only 1% of dissolved inorganic carbon in seawater exists as CO2. Thus the majority of marine macrophytes not only passively access CO2 for photosynthesis, but also actively transport CO2 and the more common bicarbonate (HCO3-, 92% of seawater dissolved inorganic carbon) into their cells. Because species with these carbon concentrating mechanisms (CCMs) are non-randomly distributed in ecosystems, we ask whether there is a phylogenetic pattern to the distribution of CCMs among algal species. To determine macrophyte traits that influence carbon uptake, we assessed 40 common macrophyte species from the rocky intertidal community of the Northeast Pacific Ocean to a) query whether macrophytes have a CCM and b) determine the evolutionary history of CCMs, using ancestral state reconstructions and stochastic character mapping based on previously published data. Thirty-two species not only depleted CO2, but also concentrated and depleted HCO3-, indicative of a CCM. While analysis of CCMs as a continuous trait in 30 families within Phylum Rhodophyta showed a significant phylogenetic signal under a Brownian motion model, analysis of CCMs as a discrete trait (presence or absence) indicated that red algal families are more divergent than expected in their CCM presence or absence; CCMs are a labile trait within the Rhodophyta. In contrast, CCMs were present in each of 18 Ochrophyta families surveyed, indicating that CCMs are highly conserved in the brown algae. The trait of CCM presence or absence was largely conserved within Families. Fifteen of 23 species tested also changed the seawater buffering capacity, or Total Alkalinity (TA), shifting DIC composition towards increasing concentrations of HCO3- and CO2 for photosynthesis. Manipulating the external TA of the local environment may influence carbon availability in boundary layers and areas of low water mixing, offering an additional mechanism to increase CO2 availability. PMID- 27415006 TI - Prognostic Impact of Combined Contrast-Induced Acute Kidney Injury and Hypoxic Liver Injury in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results from INTERSTELLAR Registry. AB - BACKGROUND: Besides contrast-induced acute kidney injury(CI-AKI), adscititious vital organ damage such as hypoxic liver injury(HLI) may affect the survival in patients with ST-elevation myocardial infarction (STEMI). We sought to evaluate the prognostic impact of CI-AKI and HLI in STEMI patients who underwent primary percutaneous coronary intervention (PCI). METHODS: A total of 668 consecutive patients (77.2% male, mean age 61.3+/-13.3 years) from the INTERSTELLAR STEMI registry who underwent primary PCI were analyzed. CI-AKI was defined as an increase of >=0.5 mg/dL in serum creatinine level or 25% relative increase, within 48h after the index procedure. HLI was defined as >=2-fold increase in serum aspartate transaminase above the upper normal limit on admission. Patients were divided into four groups according to their CI-AKI and HLI states. Major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of all-cause mortality, non-fatal MI, non-fatal stroke, ischemia-driven target lesion revascularization and target vessel revascularization were recorded. RESULTS: Over a mean follow-up period of 2.2+/-1.6 years, 94 MACCEs occurred with an event rate of 14.1%. The rates of MACCE and all-cause mortality were 9.7% and 5.2%, respectively, in the no organ damage group; 21.3% and 21.3% in CI-AKI group; 18.5% and 14.6% in HLI group; and 57.7% and 50.0% in combined CI-AKI and HLI group. Survival probability plots of composite MACCE and all-cause mortality revealed that the combined CI-AKI and HLI group was associated with the worst prognosis (p<0.0001 for both). CONCLUSION: Combined CI-AKI after index procedure and HLI on admission is associated with poor clinical outcomes in patients with STEMI who underwent primary PCI. (INTERSTELLAR ClinicalTrials.gov number, NCT02800421.). PMID- 27415007 TI - Tracing QTLs for Leaf Blast Resistance and Agronomic Performance of Finger Millet (Eleusine coracana (L.) Gaertn.) Genotypes through Association Mapping and in silico Comparative Genomics Analyses. AB - Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf blast occurs at early crop stage and is highly damaging. Mapping of resistance genes and other quantitative trait loci (QTLs) for agronomic performance can be of great use for improving finger millet genotypes. Evaluation of one hundred and twenty-eight finger millet genotypes in natural field conditions revealed that leaf blast caused severe setback on agronomic performance for susceptible genotypes, most significant traits being plant height and root length. Plant height was reduced under disease severity while root length was increased. Among the genotypes, IE4795 showed superior response in terms of both disease resistance and better agronomic performance. A total of seven unambiguous QTLs were found to be associated with various agronomic traits including leaf blast resistance by association mapping analysis. The markers, UGEP101 and UGEP95, were strongly associated with blast resistance. UGEP98 was associated with tiller number and UGEP9 was associated with root length and seed yield. Cross species validation of markers revealed that 12 candidate genes were associated with 8 QTLs in the genomes of grass species such as rice, foxtail millet, maize, Brachypodium stacei, B. distachyon, Panicum hallii and switchgrass. Several candidate genes were found proximal to orthologous sequences of the identified QTLs such as 1,4-beta-glucanase for leaf blast resistance, cytokinin dehydrogenase (CKX) for tiller production, calmodulin (CaM) binding protein for seed yield and pectin methylesterase inhibitor (PMEI) for root growth and development. Most of these QTLs and their putatively associated candidate genes are reported for first time in finger millet. On validation, these novel QTLs may be utilized in future for marker assisted breeding for the development of fungal resistant and high yielding varieties of finger millet. PMID- 27415008 TI - CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART. AB - HIV persists in a small pool of latently infected cells despite antiretroviral therapy (ART). Identifying cellular markers expressed at the surface of these cells may lead to novel therapeutic strategies to reduce the size of the HIV reservoir. We hypothesized that CD4+ T cells expressing immune checkpoint molecules would be enriched in HIV-infected cells in individuals receiving suppressive ART. Expression levels of 7 immune checkpoint molecules (PD-1, CTLA 4, LAG-3, TIGIT, TIM-3, CD160 and 2B4) as well as 4 markers of HIV persistence (integrated and total HIV DNA, 2-LTR circles and cell-associated unspliced HIV RNA) were measured in PBMCs from 48 virally suppressed individuals. Using negative binomial regression models, we identified PD-1, TIGIT and LAG-3 as immune checkpoint molecules positively associated with the frequency of CD4+ T cells harboring integrated HIV DNA. The frequency of CD4+ T cells co-expressing PD-1, TIGIT and LAG-3 independently predicted the frequency of cells harboring integrated HIV DNA. Quantification of HIV genomes in highly purified cell subsets from blood further revealed that expressions of PD-1, TIGIT and LAG-3 were associated with HIV-infected cells in distinct memory CD4+ T cell subsets. CD4+ T cells co-expressing the three markers were highly enriched for integrated viral genomes (median of 8.2 fold compared to total CD4+ T cells). Importantly, most cells carrying inducible HIV genomes expressed at least one of these markers (median contribution of cells expressing LAG-3, PD-1 or TIGIT to the inducible reservoir = 76%). Our data provide evidence that CD4+ T cells expressing PD-1, TIGIT and LAG-3 alone or in combination are enriched for persistent HIV during ART and suggest that immune checkpoint blockers directed against these receptors may represent valuable tools to target latently infected cells in virally suppressed individuals. PMID- 27415009 TI - FAM19A4 methylation analysis in self-samples compared with cervical scrapes for detecting cervical (pre)cancer in HPV-positive women. AB - BACKGROUND: High-risk human papillomavirus (hrHPV)-positive women require triage to identify those with cervical high-grade intraepithelial neoplasia and cancer (?CIN3 (cervical intraepithelial neoplasia grade 3)). FAM19A4 methylation analysis, which detects advanced CIN and cancer, is applicable to different sample types. However, studies comparing the performance of FAM19A4 methylation analysis in hrHPV-positive self-samples and paired physician-taken scrapes are lacking. METHODS: We compared the performance of FAM19A4 methylation analysis (and/or HPV16/18 genotyping) in self-samples and paired physician-taken scrapes for ?CIN3 detection in hrHPV-positive women (n=450,18-66 years). RESULTS: Overall FAM19A4 methylation levels between sample types were significantly correlated, with strongest correlation in women with ?CIN3 (Spearman's rho 0.697, P<0.001). The performance of FAM19A4 methylation analysis and/or HPV16/18 genotyping did not differ significantly between sample types. In women ?30 years, ?CIN3 sensitivity of FAM19A4 methylation analysis was 78.4% in self-samples and 88.2% in scrapes (ratio 0.89; CI: 0.75-1.05). In women <30 years, ?CIN3 sensitivities were 37.5% and 45.8%, respectively (ratio 0.82; CI: 0.55-1.21). In both groups, ?CIN3 specificity of FAM19A4 methylation analysis was significantly higher in self-samples compared with scrapes. CONCLUSIONS: FAM19A4 methylation analysis in hrHPV-positive self-samples had a slightly lower sensitivity and a higher specificity for ?CIN3 compared with paired physician-taken scrapes. With a similarly good clinical performance in both sample types, combined FAM19A4 methylation analysis and HPV16/18 genotyping provides a feasible triage strategy for hrHPV-positive women, with direct applicability on self-samples. PMID- 27415010 TI - Clinical and microarray analysis of breast cancers of all subtypes from two prospective preoperative chemotherapy studies. AB - BACKGROUND: We aimed to analyse clinical and gene expression profiles to predict pathologic complete response and disease-free survival using two consecutive, prospective, preoperative chemotherapy trial cohorts. METHODS: Clinicopathological and gene expression data were evaluated in a cohort from two consecutive phase II preoperative studies that included patients with stage IIA IIIC breast cancer of all subtypes. Analysed specimens were obtained before preoperative chemotherapy, and cDNA microarray analyses were performed using the Affymetrix Gene Chip U133 plus 2.0. RESULTS: Between December 2005 and December 2010, 122 patients were analysed. The pathologic complete response rate was significantly higher in HER2+ and HR-/HER2- cancers. Age, pathologic complete response, HR-/HER2- status, and lymph node positivity (?4) were significant poor prognostic factors for disease-free survival. For the cDNA microarray analyses, sufficient tumour samples were available from 78 of the 107 patients (73%). An 8 gene signature predictive of pathologic complete response and a 17-gene signature predictive of prognosis were identified. Patients were categorised into low-risk (n=45) and high-risk groups (n=33) (HR 70.0, P=0.004). CONCLUSIONS: This study yielded preliminary data on the expression of specific genes predicting pathologic complete response and disease-free survival in a cohort of chemonaive breast cancer patients. Further validation may distinguish those who would benefit most from perioperative chemotherapy as well as those needing further intervention. PMID- 27415011 TI - Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung. AB - BACKGROUND: Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. METHODS: Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFR expression. RESULTS: Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. CONCLUSIONS: Most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis. PMID- 27415012 TI - ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells. AB - BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells+/-the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients. PMID- 27415013 TI - Extracellular matrix composition defines an ultra-high-risk group of neuroblastoma within the high-risk patient cohort. AB - BACKGROUND: Although survival for neuroblastoma patients has dramatically improved in recent years, a substantial number of children in the high-risk subgroup still die. METHODS: We aimed to define a subgroup of ultra-high-risk patients from within the high-risk cohort. We used advanced morphometric approaches to quantify and characterise blood vessels, reticulin fibre networks, collagen type I bundles, elastic fibres and glycosaminoglycans in 102 high-risk neuroblastomas specimens. The Kaplan-Meier method was used to correlate the analysed elements with survival. RESULTS: The organisation of blood vessels and reticulin fibres in neuroblastic tumours defined an ultra-high-risk patient subgroup with 5-year survival rate <15%. Specifically, tumours with irregularly shaped blood vessels, large sinusoid-like vessels, smaller and tortuous venules and arterioles and with large areas of reticulin fibres forming large, crosslinking, branching and haphazardly arranged networks were linked to the ultra-high-risk phenotype. CONCLUSIONS: We demonstrate that quantification of tumour stroma components by morphometric techniques has the potential to improve risk stratification of neuroblastoma patients. PMID- 27415015 TI - From Motion to Emotion: Accelerometer Data Predict Subjective Experience of Music. AB - Music is often discussed to be emotional because it reflects expressive movements in audible form. Thus, a valid approach to measure musical emotion could be to assess movement stimulated by music. In two experiments we evaluated the discriminative power of mobile-device generated acceleration data produced by free movement during music listening for the prediction of ratings on the Geneva Emotion Music Scales (GEMS-9). The quality of prediction for different dimensions of GEMS varied between experiments for tenderness (R12(first experiment) = 0.50, R22(second experiment) = 0.39), nostalgia (R12 = 0.42, R22 = 0.30), wonder (R12 = 0.25, R22 = 0.34), sadness (R12 = 0.24, R22 = 0.35), peacefulness (R12 = 0.20, R22 = 0.35) and joy (R12 = 0.19, R22 = 0.33) and transcendence (R12 = 0.14, R22 = 0.00). For others like power (R12 = 0.42, R22 = 0.49) and tension (R12 = 0.28, R22 = 0.27) results could be almost reproduced. Furthermore, we extracted two principle components from GEMS ratings, one representing arousal and the other one valence of the experienced feeling. Both qualities, arousal and valence, could be predicted by acceleration data, indicating, that they provide information on the quantity and quality of experience. On the one hand, these findings show how music-evoked movement patterns relate to music-evoked feelings. On the other hand, they contribute to integrate findings from the field of embodied music cognition into music recommender systems. PMID- 27415014 TI - Diversity of Cultivated Fungi Associated with Conventional and Transgenic Sugarcane and the Interaction between Endophytic Trichoderma virens and the Host Plant. AB - Plant-associated fungi are considered a vast source for biotechnological processes whose potential has been poorly explored. The interactions and diversity of sugarcane, one of the most important crops in Brazil, have been rarely studied, mainly concerning fungal communities and their interactions with transgenic plants. Taking this into consideration, the purpose of this study was, based on culture dependent strategy, to determine the structure and diversity of the fungal community (root endophytes and rhizosphere) associated with two varieties of sugarcane, a non-genetically modified (SP80-1842) variety and its genetically modified counterpart (IMI-1, expressing imazapyr herbicide resistance). For this, the sugarcane varieties were evaluated in three sampling times (3, 10 and 17 months after planting) under two crop management (weeding and herbicide treatments). In addition, a strain of Trichoderma virens, an endophyte isolated from sugarcane with great potential as a biological control, growth promotion and enzyme production agent, was selected for the fungal-plant interaction assays. The results of the isolation, characterization and evaluation of fungal community changes showed that the sugarcane fungal community is composed of at least 35 different genera, mostly in the phylum Ascomycota. Many genera are observed at very low frequencies among a few most abundant genera, some of which were isolated from specific plant sites (e.g., the roots or the rhizosphere). An assessment of the possible effects upon the fungal community showed that the plant growth stage was the only factor that significantly affected the community's structure. Moreover, if transgenic effects are present, they may be minor compared to other natural sources of variation. The results of interaction studies using the Green fluorescent protein (GFP)-expressing T. virens strain T.v.223 revealed that this fungus did not promote any phenotypic changes in the host plant and was found mostly in the roots where it formed a dense mycelial cover and was able to penetrate the intercellular spaces of the root epidermis upper layers. The ability of T. virens to colonize plant roots suggests a potential for protecting plant health, inhibiting pathogens or inducing systemic resistance. PMID- 27415016 TI - Recent Duplication and Functional Divergence in Parasitic Nematode Levamisole Sensitive Acetylcholine Receptors. AB - Helminth parasites rely on fast-synaptic transmission in their neuromusculature to experience the outside world and respond to it. Acetylcholine plays a pivotal role in this and its receptors are targeted by a wide variety of both natural and synthetic compounds used in human health and for the control of parasitic disease. The model, Caenorhabditis elegans is characterized by a large number of acetylcholine receptor subunit genes, a feature shared across the nematodes. This dynamic family is characterized by both gene duplication and loss between species. The pentameric levamisole-sensitive acetylcholine receptor has been characterized from C. elegans, comprised of five different subunits. More recently, cognate receptors have been reconstituted from multiple parasitic nematodes that are found to vary in subunit composition. In order to understand the implications of receptor composition change and the origins of potentially novel drug targets, we investigated a specific example of subunit duplication based on analysis of genome data for 25 species from the 50 helminth genome initiative. We found multiple independent duplications of the unc-29, acetylcholine receptor subunit, where codon substitution rate analysis identified positive, directional selection acting on amino acid positions associated with subunit assembly. Characterization of four gene copies from a model parasitic nematode, Haemonchus contortus, demonstrated that each copy has acquired unique functional characteristics based on phenotype rescue of transgenic C. elegans and electrophysiology of receptors reconstituted in Xenopus oocytes. We found evidence that a specific incompatibility has evolved for two subunits co expressed in muscle. We demonstrated that functional divergence of acetylcholine receptors, driven by directional selection, can occur more rapidly than previously thought and may be mediated by alteration of receptor assembly. This phenomenon is common among the clade V parasitic nematodes and this work provides a foundation for understanding the broader context of changing anthelmintic drug targets across the parasitic nematodes. PMID- 27415019 TI - From Ordinary to Extraordinary: Insights into the Formation Mechanism and pH Dependent Assembly/Disassembly of Nanojars. AB - Nanojars are large (2 nm wide) anion-incarcerating coordination complexes of the composition [anion?{Cu(MU-OH)(MU-pz)}n] (n = 27-36), formed by the self-assembly of simple Cu(2+), HO(-), and pyrazolate (pz(-) = C3H3N2(-)) ions in the presence of certain anions with large hydration energy (e.g., CO3(2-), SO4(2-), PO4(3-), HPO4(2-)). Nanojars display spectacular chemical properties, such as unparalleled anion binding strength and, as shown herein, extraordinary resistance to extreme alkalinities (10 M NaOH). To shed light on the mechanism of the self-assembly process leading to these distinctive constructs, we employed an array of complementary techniques including mass spectrometry, pH titration, UV-vis and NMR spectroscopies, chemical synthesis, and single-crystal X-ray diffraction. In the reaction of Cu(NO3)2, pyrazole, NaOH, and Na2CO3 in tetrahydrofuran (THF), the first major intermediate is a trinuclear copper pyrazolate complex, [Cu3(MU3 OH)(MU-pz)3(NO3)2(H2O)], which was separately isolated and characterized. As the THF-insoluble NaOH slowly reacts, the nitrate ions are gradually precipitated out as NaNO3 and replaced by hydroxide ions. The resulting species, [Cu3(MU3-OH)(MU pz)3(OH)x(NO3)3-x](-) (x = 1-3), have unstable terminal Cu-OH groups and react with each other to yield OH-bridged units, such as [Cu3(MU3-OH)(MU pz)3(NO3)2]2(MU-OH) and then [{Cu3(MU3-OH)(MU-pz)3(MU-OH)2}x(NaNO3)y(Na2CO3)z] oligomers. The Cu3(OH)3(pz)3 repeating units of these oligomers have the same composition as the [Cu(OH)(pz)]n (n = 3x) nanojars and rearrange to the final products, Na2[CO3?{Cu(MU-OH)(MU-pz)}n] (n = 27, 29, 31), while eliminating the last amounts of NaNO3. pH titration, UV-vis monitoring, and chemical synthesis also confirm the formation of the trinuclear intermediate, followed by its clean transformation to nanojars. While displaying an unusual stability to high pH, nanojars are sensitive to acids stronger than water, a property exploitable for the recovery of the incarcerated anion. On lowering the pH, nanojars first break down to trinuclear complexes and finally to copper ions and pyrazole. This process is fully reversible, and nanojars are reassembled as pH is increased. PMID- 27415017 TI - Understanding the Public's Reservations about Broad Consent and Study-By-Study Consent for Donations to a Biobank: Results of a National Survey. AB - Researchers and policymakers do not agree about the most appropriate way to get consent for the use of donations to a biobank. The most commonly used method is blanket-or broad-consent where donors allow their donation to be used for any future research approved by the biobank. This approach does not account for the fact that some donors may have moral concerns about the uses of their biospecimens. This problem can be avoided using "real-time"-or study-by-study consent, but this policy places a significant burden on biobanks. In order to better understand the public's preferences regarding biobank consent policy, we surveyed a sample that was representative of the population of the United States. Respondents were presented with 5 biobank consent policies and were asked to indicate which policies were acceptable/unacceptable and to identify the best/worst policies. They were also given 7 research scenarios that could create moral concern (e.g. research intending to make abortions safer and more effective) and asked how likely they would be to provide broad consent knowing that their donation might be used in that research. Substantial minorities found both broad and study-by-study consent to be unacceptable and identified those two options as the worst policies. Furthermore, while the type of moral concern (e.g., regarding abortion, the commercial use of donations, or stem cell research) had no effect on policy preferences, an increase in the number of research scenarios generating moral concerns was related to an increased likelihood of finding broad consent to be the worst policy. The rejection of these ethically problematic and costly extremes is good news for biobanks. The challenge now is to design a policy that combines consent with access to information in a way that assures potential donors that their interests and moral concerns are being respected. PMID- 27415020 TI - Sensitivity to ozone: could it be related to an individual's complement of antioxidants in lung epithelium lining fluid? AB - Ozone, though not a free radical species, mediates its toxic effects through free radical reactions as a consequence of its high redox potential. Upon inspiration the first physical interface encountered by ozone is a thin layer of aqueous material, the epithelium lining fluid (ELF) which overlays, and is partially derived from, the underlying pulmonary epithelium. ELF is the first physical interface encountered by ozone and the majority of its primary actions are confined to this compartment. ELF contains a range of antioxidants, including the small molecular weight antioxidants: uric acid (UA), ascorbic acid (AH2) and reduced glutathione (GSH). These compounds are present in large quantities and display high intrinsic reactivities toward ozone, consistent with their role as sacrificial substrates in this setting. In this paper we examine the concept that antioxidants, in ELF, represent the first tier of defence against the oxidizing effects of ozone. Since the concentration of these antioxidants appears to differ between individuals, we propose that these protective substances may dictate, in part, an individual's sensitivity to oxidizing air pollutants such as ozone. PMID- 27415018 TI - Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells. AB - Obesity is a well-known risk factor for breast cancer development in postmenopausal women. High insulin and leptin levels seem to have a role modulating the growth of these tumours. Sam68 is an RNA-binding protein with signalling functions that has been found to be overexpressed in breast cancer. Moreover, Sam68 may be recruited to insulin and leptin signalling pathways, mediating its effects on survival, growth and proliferation in different cellular types. We aimed to study the expression of Sam68 and its phosphorylation level upon insulin and leptin stimulation, and the role of Sam68 in the proliferative effect and signalling pathways that are activated by insulin or leptin in human breast adenocarcinoma cells. In the human breast adenocarcinoma cell lines MCF7, MDA-MB-231 and BT-474, Sam68 protein quantity and gene expression were increased upon leptin or insulin stimulation, as it was checked by qPCR and immunoblot. Moreover, both insulin and leptin stimulation promoted an increase in Sam68 tyrosine phosphorylation and negatively regulated its RNA binding capacity. siRNA was used to downregulate Sam68 expression, which resulted in lower proliferative effects of both insulin and leptin, as well as a lower activation of MAPK and PI3K pathways promoted by both hormones. These effects may be partly explained by the decrease in IRS-1 expression by down-regulation of Sam68. These results suggest the participation of Sam68 in both leptin and insulin receptor signaling in human breast cancer cells, mediating the trophic effects of these hormones in proliferation and cellular growth. PMID- 27415021 TI - Increased levels of plasma 8-EPI-PGF2alpha in patients with end stage renal failure. AB - F2-isoprostanes are a series of prostaglandin-F2 like compounds specifically derived from peroxidation of arachidonic acid by a mechanism independent of the cyclooxygenase pathway. Of these, 8-epi PGF2alpha is shown to be a potent vasoconstrictor. In this study, we have analysed plasma 8-epi PGF2alpha as a marker of oxidative stress in patients with end stage renal failure (ESRF) undergoing haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Plasma F2-isoprostanes were isolated by solid-phase extraction on a C18 followed by an NH2 cartridge. Quantitative analysis of the F2-isoprostanes as pentafluorobenzyl (PFB) ester/trimethylsilyl (TMS) ether derivatives was carried out by gas chromatography-electron capture mass spectrometry. For 34 individuals with ESRF, the mean level of esterified 8-epi PGF2alpha was 0.58 +/- 0.22 M; range 0.21-1.16 nM. 8-epi PGF2alpha concentration in the patient groups was markedly higher (P<0.0005 by separate variance t-test) than that of control subjects (n=15) 0.28 +/- 0.17 nM; range 0.02-0.63 nM. There was no difference in levels of 8-epi PGF2alpha in plasma from patients undergoing HD or CAPD, nor was there any association with age, plasma lipids or plasma creatinine. These data provide direct evidence of increased oxidative stress in individuals with ESRF. This marker should be useful in clinical studies examining the degree of oxidative stress in vivo and the therapeutic impact of antioxidants. PMID- 27415022 TI - Acetaminophen-induced liver oxidative stress and hepatotoxicity: influence of Kupffer cell activity assessed in the isolated perfused rat liver. AB - The influence of acetaminophen (APAP) treatment (400 mg/kg) on Kupffer cell function was studied in the isolated perfused liver by colloidal carbon infusion, concomitantly with parameters related to oxidative stress (thiobarbituric acid reactants (TBARS) formation and glutathione (GSH) content) and tissue injury (sinusoidal efflux of lactate dehydrogenase (LDH)). APAP led to increased rates of hepatic TBARS formation, GSH depletion, and higher sinusoidal LDH efflux compared to control values, without changes in the basal rate of O2 consumption. In addition, APAP significantly enhanced the rate of carbon uptake by perfused livers and the associated carbon-induced O2 consumption, with carbon-induced LDH effluxes being increased by 411% over control values or by 124% compared to basal LDH release in APAP-treated rats. APAP-induced changes in liver TBARS formation and GSH levels were attenuated by gadolinium chloride (GdCl3) pretreatment, whereas those in carbon uptake, carbon-induced respiration, and LDH efflux were abolished. GdCl3 pretreatment decreased liver O2 consumption irrespectively of APAP treatment, an effect that seems to be due to depression of mitochondrial respiration. It is concluded that APAP intoxication enhances Kupffer cell function as assessed in the intact liver, which may represent an important source of reactive O2 species and chemical mediators conditioning the increased oxidative stress status and the tissue injury which developed. PMID- 27415023 TI - Pycnogenol enhances endothelial cell antioxidant defenses. AB - Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide anion (O2(-)), and hydroxyl radical (OH(*)) have been implicated in mediating various pathological events such as cancer, atherosclerosis, diabetes, ischemia, inflammatory diseases, and the aging process. The glutathione (GSH) redox cycle and antioxidant enzymes-superoxide dismutase (SOD) and catalase (CAT)-play an important role in scavenging ROS and preventing cell injury. Pycnogenol has been shown to protect endothelial cells against oxidant-induced injury. The present study determined the effects of pycnogenol on cellular metabolism of H2O2 and O2( ) and on glutathione-dependent and -independent antioxidant enzymes in bovine pulmonary artery endothelial cells (PAEC). Confluent monolayers of PAEC were incubated with pycnogenol, and oxidative stress was triggered by hypoxanthine and xanthine oxidase or H2O2. Pycnogenol caused a concentration-dependent enhancement of H2O2 and O2(-) clearance. It increased the intracellular GSH content and the activities of GSH peroxidase and GSH disulfide reductase. It also increased the activities of SOD and CAT. The results suggest that pycnogenol promotes a protective antioxidant state by upregulating important enzymatic and nonenzymatic oxidant scavenging systems. PMID- 27415024 TI - A study of photochemically-generated protein radical spin adducts on bovine serum albumin: the detection of genuine spin-trapping and artefactual, non-radical addition in the same molecule. AB - Photo-oxidation of bovine serum albumin (BSA) by porphyrins produces protein centred radicals that can be spin trapped by 3, 5-dibromo-4 nitrosobenzenesulphonic acid (DBNBS) and 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO). In the case of DMPO, a thiyl radical from the Cys-34 residue is trapped, whereas with DBNBS signals from both this thiyl and tertiary carbon-centred species are observed. However, specific chemical modification of the Cys-34 residue, in combination with dual-isotope spin-trapping techniques, shows that the signal assigned to the Cys-34 thiyl adduct with DBNBS is a nitroxide artefact resulting from sequential (non-radical) nucleophilic addition and oxidation. In contrast, both the Cys-34 thiyl DMPO adduct and the tertiary carbon-centred DBNBS adducts result from genuine spintrapping. This study shows that such artefacts can be detected-even with anisotropic EPR spectra-through the use of appropriately substituted spin-traps, and that nitroso spin-traps need to be employed with great care in systems containing free thiol groups. PMID- 27415025 TI - Simultaneous automated measurement of total 'antioxidant' (reducing) capacity and ascorbic acid concentration. AB - Biochemical tests of antioxidant status may be useful in measuring oxidative stress, however the time, skills and resources required for most such tests have limited their application and evaluation. In this study, newly available tests for two indices of antioxidant status, ferric reducing ability of plasma (FRAP) and ascorbic acid, were combined in one simple, rapid, automated test, referred to as FRASC. Results are available within 5 min of sample/reagent mixing. Linear dose-response is seen over a wide concentration range for both parameters. In- and between- run CVs were <1.0% and <3.0% respectively at 900-1800 MUmol/l FRAP, and <5.0% for both at 20-400 MUmol/l ascorbic acid. Mean (SD) FRAP values and ascorbic acid concentrations of fasting plasma from 130 healthy adults were 1018 (198) and 51 (18) MUmol/l respectively. This combined test is straightforward and inexpensive, and lends itself to the measurement of 'antioxidant' (reducing) capacity and ascorbic acid concentrations of various biological fluids, as well as extracts of drugs and foodstuffs. FRASC will, therefore, facilitate experimental and clinical studies of pro-oxidant: antioxidant balance and oxidative stress-related disease. PMID- 27415026 TI - Antioxidant properties of ferulic acid dimers. AB - Dimers of ferulic acid were chemically synthesized and the antioxidant properties assessed using (a) inhibition of ascorbate/iron-induced peroxidation of phosphatidylcholine liposomes and (b) scavenging of the radical cation of 2, 2' azinobis (3-ethyl-benzothiazoline-6-sulphonate (ABTS) relative to the water soluble vitamin E analogue, Trolox C (expressed as Trolox C equivalent antioxidant capacity, TEAC). The dimers examined were (E, E)-4, 4'- dihydroxy-5, 5'-dimethoxy-3, 3'-bicinnamic acid (5-5' diFA), trans-5-[(E)-2-carboxyvinyl]-2-(4 hydroxy-3-methoxy-phenyl)-7-methoxy-2, 3-dihydrobenzofuran-3-carboxylic acid (5, 8'-BenDiFA) and the methyl ester of 5, 8'-BenDiFA, dimethyl-5, 8'-BenDiFA. In both assays, the order of antioxidant efficacy was: 5, 5'-diFA > 5, 8'-BenDiFA > dimethyl-5, 8'-BenDiFA. From these results, methyl esterification decreases the antioxidant action. Comparison of the TEAC values shows that 1 mol of each of the ferulic acid dimers tested is less effective than 2 mol of free ferulic acid, and so dimerization decreases antioxidant action of these hydroxycinnamates. PMID- 27415027 TI - Semiquinone production by lipophilic o-naphthoquinones. AB - Several beta-lapachone analogues, the o-naphthoquinones CG 10-248, CG 9-442 and CG 8-935, were reduced to their semiquinones by sodium borohydride, the liver NADPH-P450 reductase system and Crithidia fasciculata cells, in anaerobic solutions. ESR spectra of the radical anions showed hyperfine spin couplings located at protons of the naphthalene ring. Borohydride reduction of another o naphthoquinone, mansonone E, yielded spin couplings located at the naphthalene and methyl groups protons. The symmetrical polarized carbonyl groups were essential for electron capture and semiquinone production. These observations support the idea that quinones are capable of redox-cycling and oxygen radical generation. PMID- 27415028 TI - Correspondence. PMID- 27415029 TI - Correlation between Photovoltaic Performance and Interchain Ordering Induced Delocalization of Electronics States in Conjugated Polymer Blends. AB - In this paper we correlate the solar cell performance with bimolecular packing of donor:acceptor bulk heterojunction (BHJ) organic solar cells (OSCs), where interchain ordering of the donor molecule and its influence on morphology, optical properties, and charge carrier dynamics of BHJ solar cells are studied in detail. Solar cells that are fabricated using more ordered defect free 100% regioregular poly(3-hexylthiophene) (DF-P3HT) as the donor polymer show ca. 10% increase in the average power conversion efficiency (PCE) when compared to that of the solar cell fabricated using 92% regioregularity P3HT, referred to as rr P3HT. EQE and UV-vis absorption spectrum show a clear increase in the 607 nm vibronic shoulder of the DF-P3HT blend suggesting better interchain ordering which was also reflected in the less Urbach energy (Eu) value for this system. The increase in ordering inside the blend has enhanced the hole-mobility which is calculated from the single carrier device J-V characteristics. Electroluminance (EL) studies on the DF-P3HT system showed a red-shifted peak when compared to rr P3HT-based devices suggesting low CT energy states in DF-P3HT. The morphologies of the blend films are studied using AFM and grazing-incidence wide-angle X-ray scattering (GIWAXS) suggesting increase in the roughness and phase segregation which could enhance the internal scattering of the light inside the device and improvement in the crystallinity along alkyl and pi-stacking direction. Hence, higher PCE, lower Eu, red-shifted EL emission, high hole-mobility, and better crystallinity suggest improved interchain ordering has facilitated a more delocalized HOMO state in DF-P3HT-based BHJ solar cells. PMID- 27415030 TI - Patient Safety and Methylene Blue-Associated Severe Serotonin Toxicity. PMID- 27415031 TI - Different Platelet Count Thresholds to Guide Use of Prophylactic Platelet Transfusions for Patients With Hematological Disorders After Myelosuppressive Chemotherapy or Stem Cell Transplantation. AB - CLINICAL QUESTION: What is the optimal platelet count threshold for prophylactic platelet transfusions to minimize bleeding, platelet use, and adverse clinical outcomes in thrombocytopenic patients with hematological malignant neoplasms? BOTTOM LINE: Maintaining a higher platelet count threshold (<=20 * 109/L or <=30 * 109/L) was not associated with less bleeding than the current standard (<=10 * 109/L), but required more platelet transfusions (low-quality evidence). PMID- 27415032 TI - Reliability of a Standardized Nasal Anatomic Worksheet and Correlation With Subjective Nasal Airway Obstruction. AB - Importance: Nasal obstruction is a common chief concern; however, a comprehensive standardized worksheet for evaluating nasal obstruction has not been developed. Objective: To evaluate the interrater reliability between staff surgeons and otolaryngology residents using a worksheet-based standardized nasal examination and to identify specific examination findings correlated with the Nasal Obstruction Symptom Evaluation quality-of-life score. Design, Setting, and Participants: This cross-sectional study conducted from June to July 2012 involved 50 adults presenting to an otolaryngology clinic at a tertiary care hospital. The patients were examined by 2 board-certified facial plastic surgeons and 2 otolaryngology residents. Exposures: The inferior turbinates, septum, and internal and external nasal valve narrowing and collapse were graded bilaterally from a scale of 0 to 3 with the aid of a standardized nasal anatomy worksheet. The findings were compared between the attending staff, residents, and the entire group. Main Outcomes and Measures: The Cohen kappa coefficient for interrater reliability was calculated for each of the graded metrics. The Nasal Obstruction Symptom Evaluation scores were correlated with anatomic scores. Results: Of the 49 patients included in the final analysis, the mean age was 43.6 years (range, 21-82 years), and 31 were male (66.3%). Among all attending and resident examiners, a moderate to fair, statistically significant interrater reliability coefficient (P < .001) was observed in the following nasal anatomic measurements: left and right Cottle (kappa = 0.582 [95% CI, 0.463-0.700] and kappa = 0.580 [95% CI, 0.461-0.698], respectively), modified Cottle (kappa = 0.491 [95% CI, 0.373 0.609] and kappa = 0.560 [95% CI, 0.442-0.679], respectively), dynamic internal nasal valve collapse (kappa = 0.204 [95% CI, 0.118-0.290] and kappa = 0.232 [95% CI, 0.140-0.323], respectively), and inferior turbinate hypertrophy (kappa = 0.252 [95% CI, 0.152-0.352] and kappa = 0.235 [95% CI, 0.153-0.317], respectively). The trend of examination interrater reliability was similar for attending staff and the otolaryngology residents. The Nasal Obstruction Symptom Evaluation score correlated with the mean total anatomic worksheet score (Spearman rho = 0.301; P = .048). Conclusions and Relevance: Interrater reliability is high in both residents and attending staff for dynamic nasal airway examinations evaluating the internal and external nasal valves and for turbinate hypertrophy assessment. The total nasal anatomic score using a standardized worksheet correlates to patient-reported nasal-specific quality of life. Level of Evidence: NA. PMID- 27415033 TI - Direct Chemical Fine-Tuning of Electronic Properties in Sc2 Ir6-x Pdx B. AB - Crystal orbital Hamilton population (COHP) bonding analysis has predicted that ScPd3 B0.5 is the least stable compound of the entire series Sc2 Ir6-x Pdx B. Here, we report a systematic study of Sc2 Ir6-x Pdx B (x=3, 5 and 6) by means of 11 B nuclear magnetic resonance (NMR), Knight shift (K) and nuclear spin-lattice relaxation rate (1/T1 ). NMR results combined with theoretical band structure calculations provide a measure of s- and non-s-character Fermi-level density of states. We present direct evidence that the enhanced s-state character of the Fermi level density of states (DOS) in ScPd3 B0.5 reduces the strength of the B 2p and Pd 4d hybridized states across the entire Sc2 Ir6-x Pdx B series. This hybridization strength relates to the opening of a deep pseudogap in the density of states of Sc2 IrPd5 B and the chemical bonding instability of ScPd3 B0.5 . This study is an experimental realization of a chemical fine-tuning of the electronic properties in intermetallic perovskites. PMID- 27415034 TI - Perspectives on investigational drugs and immunotherapies for glioblastoma. PMID- 27415036 TI - The Role of Veterinary Education in Safety Policies for Animal-Assisted Therapy and Activities in Hospitals and Nursing Homes. AB - Animal-assisted activities (AAA) and animal-assisted therapy (AAT) programs are increasing in popularity, but current programs vary in their safety and health policies. Veterinarians can have an important role in ensuring the safety of both the animals and humans involved, but it is unclear how best to educate veterinary students to serve effectively in this role. Therefore, the goal of this study was to assess the knowledge gaps and perceptions of first-year veterinary students on health and safety aspects of AAA/AAT programs by administering a survey. This information could then guide future educational training in veterinary schools to address the knowledge gaps in this area. Formal education during the veterinary curriculum had not yet been provided to these students on AAA/AAT before the survey. Of 98 first-year veterinary students, 91 completed the survey. When asked about policies on visiting animals, 58% of students responded that nursing homes are required to have a policy and 67% responded that hospitals are required to have one. Three quarters of students reported that veterinarians, animal handlers, and facilities should share the responsibility for ensuring safe human animal interaction in AAA/AAT programs. Most (82%) of the students responded that all or most national and local therapy animal groups prohibit animals that consume raw meat diets from participating in AAA/AAT programs. The results of this survey will help veterinary schools better identify knowledge gaps that can be addressed in veterinary curricula so future veterinarians will be equipped to provide appropriate public health information regarding AAA/AAT programs. PMID- 27415035 TI - Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature. AB - Myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonias(SCM) were belonged to Non-dystrophic myotonias, in which muscle relaxation is delayed after voluntary or evoked contraction. These diseases can not be simply distinguished only based on symptoms and signs but also on genetics: more than 100 mutations in the CLCN1 gene have been associated with MC, while at least 20 mutations in the SCN4A gene have been associated with PC and SCM. Most of these genetics studies have been conducted outside China, only several MC, PC, and SCM families accepted gene scan were reported in China. Therefore we analyzed genetic mutations in CLCN1 and SCN4A in 10 Chinese families clinically diagnosed with Non-dystrophic myotonias. Our result revealed 12 potential disease-causing mutations(3 mutations were novel) that were present in the probands and affected family members. We also reviewed all available literature on mutations linked to these 3 disease in Chinese populations. Our results may help identify genetic determinants as well as clarify genotype phenotype relationships. PMID- 27415037 TI - The State of Veterinary Dental Education in North America, Canada, and the Caribbean: A Descriptive Study. AB - Dental disease is important in the population of pets seen by veterinarians. Knowledge and skills related to oral disease and dentistry are critical entry level skills expected of graduating veterinarians. A descriptive survey on the state of veterinary dental education was sent to respondents from 35 veterinary schools in the United States, Canada, and the Caribbean. Using the online SurveyMonkey application, respondents answered up to 26 questions. Questions were primarily designed to determine the breadth and depth of veterinary dental education from didactic instruction in years 1-3 to the clinical year programs. There was an excellent response to the survey with 86% compliance. Learning opportunities for veterinary students in years 1-3 in both the lecture and laboratory environments were limited, as were the experiences in the clinical year 4, which were divided between community-type practices and veterinary dentistry and oral surgery services. The former provided more hands-on clinical experience, including tooth extraction, while the latter focused on dental charting and periodontal debridement. Data on degrees and certifications of faculty revealed only 12 programs with board-certified veterinary dentists. Of these, seven veterinary schools had residency programs in veterinary dentistry at the time of the survey. Data from this study demonstrate the lack of curricular time dedicated to dental content in the veterinary schools participating in the survey, thereby suggesting the need for veterinary schools to address the issue of veterinary dental education. By graduation, new veterinarians should have acquired the needed knowledge and skills to meet both societal demands and professional expectations. PMID- 27415038 TI - Teaching Evidence-Based Veterinary Medicine in the US and Canada. AB - There is no comprehensive review of the extent to which evidence-based veterinary medicine (EBVM) is taught in AVMA-accredited colleges of veterinary medicine in the US and Canada. We surveyed teaching faculty and librarians at these institutions to determine what EBVM skills are currently included in curricula, how they are taught, and to what extent librarians are involved in this process. Librarians appear to be an underused resource, as 59% of respondents did not use librarians/library resources in teaching EBVM. We discovered that there is no standard teaching methodology nor are there common learning activities for EBVM among our survey respondents, who represent 22 institutions. Respondents reported major barriers to inclusion such as a perceived shortage of time in an already crowded course of study and a lack of high-quality evidence and point-of-care tools. Suggestions for overcoming these barriers include collaborating with librarians and using new EBVM online teaching resources. PMID- 27415039 TI - Massive strength of the no strike policy. AB - Nurses have repeatedly seen the NHS and themselves mistreated I and abused and they require action - now. PMID- 27415041 TI - Guidelines on restraint. AB - The Royal College of Nursing this week published guidelines for the use of restraint in caring for the elderly mentally ill. PMID- 27415042 TI - Clinicians join abortion debate. AB - Clinicians last week added their weight to the abortion debate, on the eve of the second reading of David Alton's controversial Bill aiming to reduce the upper time limit for abortions to 18 weeks (see page 10 ). PMID- 27415044 TI - Transforming care could benefit both nurses and patients, says specialist. AB - By reassessing the use of care plans and focussing on a problem solving approach, the nursing care of the patient can be transformed, benefitting the patient and giving greater job satisfaction to nurses. PMID- 27415043 TI - Diabetics at end of queue. AB - Diabetics who develop end stage renal failure as a result of their condition tend to get put to the end of the queue when it comes to receiving treatment. PMID- 27415045 TI - Millions spent on psychotropic drugs. AB - The NHS spent L61.9 million on psychotropic drugs in 1986, it was revealed in Parliament last week. They include hypnotics, sedatives and tranquilisers, anti depressants, and combined anti-depressants and tranquilisers. PMID- 27415046 TI - Call for additions to drug tariff by RHA. AB - Oxford Regional Health Authority is backing a plea from pharmacists to have a small number of dressings and treatments included in the Drug Tariff. PMID- 27415047 TI - Guidelines for small hospitals. AB - Nurses in small community hospitals should use their colleagues in large district hospitals for help with clinical updating and continuing education, according to a report published last week. PMID- 27415048 TI - Asthma drug inhaler launched. AB - A new asthma drug inhaler will help patients control their symptoms better, according to asthma specialists Martyn Partridge and Bill Holmes. PMID- 27415049 TI - Coping with a heart transplant. AB - Partners of patients who undergo heart transplants experience a bewildering array of emotions, according to research from America. PMID- 27415050 TI - Risks from smokers' blood. AB - Neonates and patients with seriously compromised cardiovascular reserves should not be given blood donated by smokers, according to research from America. PMID- 27415052 TI - Screening possibility for ovarian cancer. AB - Researchers from St Bartholomew's Hospital, London looking at the possibility screening women for ovarian cancer. This cancer kills between 3,000 and 4,000 women every year - twice the number killed by cervical cancer. The five year survival rate is ten per cent. PMID- 27415051 TI - Overcoming impotence. AB - Erectile impotence in men with diabetes can be overcome using a new non-invasive device, according to research from Leeds. PMID- 27415053 TI - Need to monitor levels of albumin. AB - Raised levels of albumin in the urine of people with diabetes (microalmuniuria) is predictive of the later development of nephropathy and should be routinely monitored, according to research from Denmark. PMID- 27415054 TI - Protein may 'mop up' aids virus. AB - American scientists have synthesised a human protein that could prevent the AIDS virus from infecting immune system cells. PMID- 27415055 TI - Unions ask for meeting with PM. AB - The General Secretaries of the five major nursing unions have requested an urgent meeting with the Prime Minister to dicsuss their concerns over 'the current situation in the National Health Service.' PMID- 27415057 TI - Rcn announces plan of action. AB - A dramatic eight-point plan of action to express the 'deep anger' of nurses around the country at their pay and conditions has been adopted by the ruling Council of the Royal College of Nursing. PMID- 27415058 TI - Day of action against tendering. AB - Scottish trade unions are planning a mass day of action next month against the implementation of competitive tendering for ancillary hospital services throughout the country. PMID- 27415059 TI - College backs rise in cigarette tax. AB - The Royal College of Nursing is backing a call by the British Medical Association for a substantial increase in cigarette tax, it was announced last week. PMID- 27415060 TI - Alton bill goes to commons committee. AB - MPs last week passed the second reading of David Alton's controversial Private Member's Bill to reduce the abortion limit to 18 weeks. The votes were 296 to 251, a majority of 45. PMID- 27415061 TI - All change for community care services? AB - There are strong indications that Sir Roy Griffiths will recommend to the Prime Minister that local authorities should take charge of many community care services. PMID- 27415062 TI - Rising protests over staff shortages. AB - The Government is coming : under increasing pressure from both nurses and parents over I staff shortages in England's paediatric intensive care units. PMID- 27415063 TI - Budget falls short on AIDS care. AB - The cost of treating people with AIDS could leave the NHS some L30 million out of pocket this year, according to forecasts. PMID- 27415065 TI - No new money for NHS. AB - The Government again came under pressure last week to inject more cash into the NHS, while Health Secretary, John Moore continued to defend its record on health spending. PMID- 27415064 TI - Progress on pay awards. AB - Progress on this year's pay awards take another step forward this week, with the Staff Side of the Nursing and Midwifery Negotiating Council presenting its oral evidence to the Pay Review Body. PMID- 27415066 TI - Prospect of action increases. AB - The prospect of industrial action by nurses throughout London moved still closer last week as individual branches of both the Confederation of Health Service Employees and the National Union of Public Employees voted independently to stage 24 hour strikes. Nurses at several other hospitals were to vote this week on a ballot for strike action - the legal requirement being that such ballots must take place in secret. PMID- 27415067 TI - Adventurous expedition. AB - Enrolled nurse Joanne Smith is the latest in a lengthening list of nurses setting off on adventure expeditions. Joanne, who works on a gynaecology ward at the Gloucestershire Royal Hospital, Will set off with operation Raleigh in july, to spend three months working with a group of other young venturers in the remote appalachian mountains in the USA. PMID- 27415068 TI - Better advice for injured nurses. AB - A nurse manager who has started a system of referring work injured nurses to a link person for counselling and advice says the NHS has a big responsibility to care for its own staff. PMID- 27415069 TI - AIDS summit. AB - This week sees the launch of the first ever World Summit on AIDS, to be attended by health ministers and senior AIDS officials from over 130 countries. PMID- 27415071 TI - Hazards at work for pregnant women. AB - Senior Occupational Health nurses have welcomed a new report on health hazards to pregnant women at work. PMID- 27415070 TI - Increase in number of unqualified community nursing staff. AB - Community nursing care is increasingly being carried out by unqualified staff, according to the English National Board for Nursing, Midwifery and Health Visiting. PMID- 27415072 TI - Griffiths report eagerly awaited. AB - Sir Roy Griffiths, Mrs Thatcher's special adviser on the NHS, is due any day to present his major review of community care to ministers in an atmosphere where there is no real consensus on the way forward. PMID- 27415073 TI - Campaign a success. AB - Nursing Standard's long running and successful 'Back lo Nursing' campaign continues with two more health authorities benefiting directly from our round the country open days. PMID- 27415074 TI - AIDS forum policy statements. AB - The RCN's National Nursing Forum on AIDS is issuing its first major statements on matters of concern to those caring for HIV-positive and AIDS patients. Its policy wall be set out on the subjects of euthanasia and precautions covering blood and body fluids. The Forum, part of the RCN Oncology Nursing Society, was set up last September to campaign for better health education and care of those affected by the disease. PMID- 27415075 TI - Setting standards in radiology. AB - The RCN Radiology Special Interest Group - one of the College's newest entities - has established a committee to formulate standards for nurses working in the field of radiology. Meetings scheduled for later in the year will discuss the development of guidelines for ensuring quality of nursing care in the speciality. PMID- 27415076 TI - Funding system for congress delegates to be simplified. AB - A new, simplified system of funding branch delegates to the Royal College of Nursing Congress at Brighton this year will give branches more flexibility and cut down on bureaucracy. PMID- 27415077 TI - Shortage of applicants for en course. AB - An RCN development course for enrolled nurses could face the axe if more applicants do not come forward. According to Susan Scott, RCN Adviser for Enrolled Nurses, there have only been three applicants so far for the course, currently scheduled to run at the RCN Institute of Advanced Nursing Education from April 18 to July 15. PMID- 27415078 TI - China figures high in collection. AB - RCN President Maude Storey (left) receives two porcelain statuettes from Eileen North way, Matron in Chief of the Queer Alexandra Royal Naval Nursing Sendee. The statuettes, of a QARNNS sister and staff nurse, were cast to commemorate the sendee's center, ary in 1984 and will be added to the RCN's growing collection of nursing figurines. Also attending the presentation ceremony were (left to right) Trevor Clay. RCN General Secretary, John Kelly, Chairman of Council, and Miss Mary Featherstone-Dilkc, President of the Queen Alexandra Royal Naval Nursing Sendee Association. PMID- 27415080 TI - Oxfordshire nurse wins bussiness award. AB - Oxfordshire nurse Heather Jane Sears, who, withm five years of qualifying had scaled the promotion ladder to hospital manager, has just received a major award for her business achievements. PMID- 27415079 TI - History lessons from the archives. AB - 'Excellent nurses are having to leave Bristol because they can't get rooms for love nor money'. So runs a newspaper cutting from 1920, just one item in a fascinating collection of archive material recently presented to the Royal College of Nursing by the South Western Branch. PMID- 27415081 TI - Glasgow nurse teacher says change to achieve a more professional role. AB - Current teaching methods will have to change drastically if nurses are to achieve a more professional role, a recent study reveals. PMID- 27415082 TI - Birmingham information service for OH nurses. AB - Occupational health nurses faced with a puzzling illness at work can contact a new information service at the University of Birmingham. PMID- 27415083 TI - Isligton HA aims to set up alcohol help system. AB - Building up a community alcohol team and establishing closer links with accident and emergency staff are two of the current aims of Ralph MacCormack, Islington Health Authority's Senior Nurse Specialist on alcohol. PMID- 27415084 TI - Bristol report highlights need for services. AB - A range of community services such as chiropody, house cleaning, meals on wheels and dental care are needed to make care in the community a reality, says a report on health visitors and community nurses in Bristol. PMID- 27415086 TI - Community care teams set up in Leeds. AB - The Government's community mental health care policies will shortly be put to the test when two new projects get under way in Leeds. Two community care teams have been established by Leeds Eastern and Leeds Western DHAs, in collaboration with the city's social services, to each care for a 25,000 population. PMID- 27415085 TI - Health clinic opens for london whizz kids. AB - The fight against stress and life-style related ill health has now extended to London's financial hub, the City. PMID- 27415088 TI - West Germany. AB - Nurses in West Germany are bracing themselves in anticipation of proposed legislation this spring which aims to cut L5 billion from the health service budget. PMID- 27415087 TI - Elderly lose out in Kent home closure. AB - Nursing staff at the Emily Jackson House for disabled elderly people in Sevenoaks, Kent, have issued a statement saying the plan to close it for financial reasons will be 'most detrimental, to residents needs. PMID- 27415089 TI - Norway. AB - Norway's Labour Government has agreed to increase the number of public child care places and reduce the nurses' working week to 37V2 in a bid to beat the country's shortage of nurses. PMID- 27415090 TI - Italy. AB - New industrial problems among nurses and doctors in Italy are expected when a fresh round of pay talks are due to begin later this month. PMID- 27415091 TI - Australia. AB - A nurse has been appointed to an important job, steering national health policies for women in Australia. PMID- 27415092 TI - Czechoslovakia. AB - Midwives in Czechoslovakia have reported the lowest rate for Caesarean births in industrialised countries in Europe, the USA and the Pacific. PMID- 27415093 TI - The whole truth. AB - In Hilary Jenkins' book there is no such thing as homoeopathic nursing - which is not exactly the view you would expect from someone who is the Senior Nurse at the Royal London Homoeopathic Hospital. PMID- 27415094 TI - AIDS - safely first. AB - Amid chilling predictions that the number of people who are asymptomatically infected with the AIDS virus is set to escalate, nurses who are experts in the field have issued revised guidelines for the profession and managers. PMID- 27415095 TI - Back to nursing with confidence I Jones Back to nursing with confidence Published by Heinemann 288pp L8.50 0-433-14710-5 [Formula: see text]. AB - If, like me, you wish to return to nursing after many years' absence, Irene Jones's book should provide the encouragement to do so. Easy to read, it helps towards deciding the type of nursing to go back to and how to apply for a job. PMID- 27415097 TI - Coping with Childlessness Coping with childlessness revised edition Houghton D Houghton P Unwin Paperbacks 186pp L3.95 0-04-649054-X [Formula: see text]. AB - From their experience of being childless, Diane and Peter Houghton offer advice and consolation to others forced to reconcile themselves to a life without children of their own, and an insight to the general public and health professionals. PMID- 27415096 TI - Health and Deprivation P Townsend P Phillimore A Beattie Health and Deprivation Published by Croom Helm 212pp L19.95 0-7099-4351-2 [Formula: see text]. AB - Definitions of health range from absence of disease [Illegible Word] state of complete menTM physical and social well being. Are they individual? To what extent do wider social problems, eg. employment status, affect health Is health related to material deprivation? If so, how do we measure it? PMID- 27415098 TI - Science in Nursing L Cree and S Rischmiller Science in Nursing W B Saunders 344pp L13.95 03-900266-7 [Formula: see text]. AB - Throughout, where applicable to nursing, the sciences of biology, chemistry and physics are examined. The content is diverse, with chapters on humans and heat; the forces and mechanics of the 'human' machine; atoms, ions and molecules (atomic theory); fluids; and energy in the body. PMID- 27415099 TI - Voting holds key to success of Alton's bill. AB - The success of Liberal MP David Alton's bill seeking to reduce the time limit for abortions to no more than 18 weeks of pregnancy will largely depend on the number of votes in favour of the amendment. PMID- 27415100 TI - Complementary therapies under threat. AB - Secretory of State for Social Services, John Moore is to come under pressure to help secure the future of thousands of natural cures, currently threatened by a review of the Medicines Act. PMID- 27415101 TI - No spring cash boost punned for NHS. AB - Chancellor of the Exchequer, Nigel Law- son, is under pressure to give the health services a spring tonic in his budget. PMID- 27415102 TI - Legislation to tackle UKCC conduct cases. AB - Health ministers are considering bringing in legislation which would enable non council members to help the United Kingdom Central Council for Nursing, Midwifery and Health Visiting tackle its growing backlog of professional conduct cases. PMID- 27415103 TI - Labour fury over poll tax exemptions. AB - Proposals to exempt certain members of the armed services from paying poll tax has infuriated Labour MPs who are campaigning to get a better deal for nurses under the new community charges. PMID- 27415104 TI - Clients not patients. AB - As a student on a course which trains for mental handicap nursing, I read with keen interest your articles 'Individual Programme Planning' and 'What do mental handicap nurses do?' (Nursing Standard week ending January 16). I feel mental handicap nursing is an area which is rather unrepresented in the nursing journals. Thus I am sorry to have to write with a complaint. PMID- 27415107 TI - Tried and tested. AB - Ainna Fawcett-Henesy's letter in response to the Guardian Leader comment, November 26, quite rightly emphasised the positive aspects of the White Paper and The Health Circular on Community Nursing, namely the endorsement of the nurse practitioner and nurse prescribing. PMID- 27415105 TI - Oppose any pay cuts. AB - I hope you will allow me the right to reply to Martin J Gilli- gan's letter (Nursing Standard week ending January 9) and was pleased to see that his letter was headed 'False Assumptions' as he certainly has made at least two. PMID- 27415106 TI - Invaluable chapter. AB - May I through your pages express my pleasure to see the tremendous input by the Royal College of Nursing's Paediatric Nursing Society to the recent RCN publication. PMID- 27415108 TI - Addenbrooke's reunion. AB - It will be ten years this year since the September 1975 set qualified at Addenbrooke,s Hospital, Cambridge. PMID- 27415110 TI - A moving experience. AB - Our roundup of what's on. PMID- 27415109 TI - Plaster room problems. AB - We are organisers and teachers for a course on plaster techniques which is run under the auspices of the British Orthopaedic Association and the Royal College of Nursing Orthopaedic Nursing Forum [Illegible Word] has been in existence for the last six years. PMID- 27415111 TI - Computer logic. AB - How do civil servants tell the difference between a staff nurse and a midwife? Easy - they ask a computer. At least that's Health Minister Tony Newton's explanation. PMID- 27415112 TI - An inventive ploy. AB - Africa has already provided one of the more graphic synonyms for the disease AIDS, colloquially known in the continent as Slim Disease. PMID- 27415113 TI - Crunch issue. AB - Nurses are not the prime target for Crunchy Bar salesmen, if a report from Quaker Oats is anything to go by. PMID- 27415114 TI - Jumping the queue. AB - As nurses well know the ultra sound scan is one of the most important technological advances in medicine. PMID- 27415115 TI - Watchdog. AB - Q I am a Registered General Nurse and work as a bank nurse for both a local mainly geriatric hospital and a psychiatric one. PMID- 27415116 TI - Directions. AB - Dependency upon drugs or alcohol or, in some instances unfortunately, a combination of both is neither new nor unique to the twentieth century. A look at Hogarth's work shows also that only a few centuries back alcohol dependency was not exclusive to one sex. What is unique today, however, is the positive approach and acceptance of both for treatment within a clinical or community setting. PMID- 27415117 TI - Crossing the boards. AB - While 'moonlighting' is no longer anything new in nursing, the idea of working as a nurse to support a second career is fairly novel - especially when the second career is that of a budding writer. PMID- 27415118 TI - Listings. AB - Nursing Standard's listings section is a completely free service for its readers. To ensure maximum publicity for any event connected with your profession, be sure to let us know so that it can be included in our exhaustive (illegible word) guide to what's on in nursing. PMID- 27415119 TI - Cashless vending. AB - The plastic fantastic is coming to vending machines with the launch of cashless drinks dispensers from Four Square. PMID- 27415120 TI - Sitting comfortably? AB - Bay Jacobsen Ltd have introduced a new Therapeutic Seating System, designed for the wheelchair (illegible word) or for people who spend long hours in the car or sitting in the office. It consists of a cushion and back rest which, the manufacturers claim, protect and support the back while providing enhanced comfort. PMID- 27415121 TI - Breast help for mothers. AB - A newly designed breast shell promises to help mums with sore nipples and prevent leakages of milk onto their clothes. PMID- 27415122 TI - (illegible word) RANGE OF DISPOSABLE DRESSINGS. AB - Scott products has launched a new range of disposable paper wipers and dressings aimed specifically at the health care market. PMID- 27415123 TI - Ultrasonic cleaner. AB - Lucas Dawe has produced an ultrasonic cleaner specifically for use in hospitals. PMID- 27415124 TI - Lightweight skin stapler available. AB - A new lightweight skin stapler is now available from Davis and Geek. PMID- 27415125 TI - Zero toxicity urinary catheters. AB - A range of urinary catheters that guarantee zero toxicity is now on the market. PMID- 27415126 TI - Proof of the pudding. AB - A nutritious pudding from Cow and Gate promises to add greater variety to the diet of patients who need supplemental feeding. PMID- 27415127 TI - Savings claim for filter technology. AB - Pall Biomedical has released figures showing that the Pall Intravenous Set Saver Filter saves nurses' time and NHS money. PMID- 27415128 TI - Cleaning quietly. AB - A new 'quieter, cleaner' industrial vacuum cleaner has been produced by Trewax Manufacturing Ltd, designed with hospitals in mind. PMID- 27415129 TI - Hyper active. AB - This new outfit for x-ray work was brought out in March 1909. It looks extremely heavy and uncomfortable but certainly covers up a vast majority of the body. The Nursing Standard is looking for an imaginative caption to complete this picture, which should be sent on a postcard to Caption Competition, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, HA1 2AX. The winner will receive a L10 book token. Closing date February 3 and the winner will be announced February 10. PMID- 27415130 TI - Seeking an objective diagnosis of depression. AB - Major depressive disorder (MDD: unipolar depression) is widely distributed in the USA and world-wide populations and it is one of the leading causes of disability in both adolescents and adults. Traditional diagnostic approaches for MDD are based on patient interviews, which provide a subjective assessment of clinical symptoms which are frequently shared with other maladies. Reliance upon clinical assessments and patient interviews for diagnosing MDD is frequently associated with misdiagnosis and suboptimal treatment outcomes. As such, there is increasing interest in the identification of objective methods for the diagnosis of depression. Newer technologies from genomics, transcriptomics, proteomics, metabolomics and imaging are technically sophisticated and objective but their application to diagnostic tests in psychiatry is still emerging. This brief overview evaluates the technical basis for these technologies and discusses how the extension of their clinical performance can lead to an objective diagnosis of MDD. PMID- 27415131 TI - The relation of social support and depression in patients with chronic low back pain. AB - PURPOSE: Depression is a common condition in adults with low back pain (LBP), and is associated with poorer patient outcomes. Social support is a modifiable factor that may influence depressive symptoms in people with LBP and, if so, could be a consideration in LBP management when depression is an issue. The aim of this study was to examine social support as a prognostic factor for depressive symptoms and recovery from depression in patients with LBP. METHOD: Patients with LBP (n = 483), recruited from four imaging centers in Canada, completed an initial survey following imaging and a follow-up survey one year later, including the Medical Outcomes Study (MOS) Social Support Survey and the Center for Epidemiologic Studies Depression Scale. Multivariable regression analyses were used to examine the relationship between social support and depression. RESULTS: More social support (overall functional social support) at baseline was associated with recovery from depression (OR = 0.24; 95% CI 0.10, 0.55) and less depressive symptoms (beta = 1.68; 95% CI = 0.36, 3.00) at one-year follow-up. In addition, associations were found between specific aspects (subscales) of social support and the two depression outcomes. CONCLUSIONS: Functional social support as a prognostic factor for depression and possible target of LBP management warrants further investigation. Implications for Rehabilitation Depression is a common condition in adults with low back pain (LBP), and is associated with poorer patient outcomes. This study provides evidence for social support as a prognostic factor for depressive symptoms and recovery from depression in patients with LBP problems. Management of pain conditions may be enhanced by a better understanding of modifiable risk factors for depression, such as social support. PMID- 27415133 TI - Coming in postgraduate medicine. PMID- 27415134 TI - Problems solutions. PMID- 27415132 TI - MYC2, MYC3, and MYC4 function redundantly in seed storage protein accumulation in Arabidopsis. AB - Basic helix-loop-helix transcription factors (TFs), namely MYC2, MYC3, and MYC4, interact with Jasmonate Zim-domain proteins and are their direct targets. These TFs have been shown to function synergistically to control Arabidopsis growth and development. Our results showed similar MYC2, MYC3, and MYC4 expression patterns during Arabidopsis seed development, which remained relatively high during seed mid-maturation. MYC2, MYC3, and MYC4 acted redundantly in seed size, weight control, and in regulating seed storage protein accumulation. Triple mutants produced the largest seeds and single and double mutants' seeds were much larger than those of wild type. The weight of triple mutants' seeds was significantly higher than that of wild-type seeds, which was accompanied by an increase in seed storage protein contents. Triple mutants' seeds presented a marked decrease in 2S amounts relative to those in wild-type seeds. Liquid chromatography tandem mass spectra sequencing results indicated that both the relative abundance and the peptide number of CRA1 and CRU3 were greatly increased in triple mutants compared to wild type. The expression of 2S1-2S5 decreased and that of CRA1 and CRU3 increased in triple mutants relative to those in wild types during seed development, which might have contributed to the low 2S and high 12S contents in triple mutants. Our results contribute to understanding the function of MYC2, MYC3, and MYC4 on seed development, and provide promising targets for genetic manipulations of protein-producing crops to improve the quantity and quality of seed storage proteins. PMID- 27415136 TI - What's happening in medicine. PMID- 27415135 TI - Editor's mail. PMID- 27415137 TI - Washington background. PMID- 27415138 TI - Physician-at-large. PMID- 27415139 TI - Viral and mycoplasmal pneumonias. AB - Many different agents are known to cause nonbacterial pneumonias, but the clinical findings may not vary. An understanding of the epidemiology and pathogenesis of these infections-as well as the possible etiologic agents-is important in diagnosis, prevention, and treatment. Although treatment is now mainly symptomatic, new antiviral agents will soon be available for specific therapy. PMID- 27415142 TI - Therapeutic index to advertisers. PMID- 27415141 TI - Answers cme credit quiz. PMID- 27415144 TI - Economic Hydrophobicity Triggering of CO2 Photoreduction for Selective CH4 Generation on Noble-Metal-Free TiO2-SiO2. AB - On the basis of the fact that the competitive adsorption between CO2 and H2O on the catalyst plays an important role in the CO2 photoreduction process, here we develop an economic NH4F-induced hydrophobic modification strategy to enhance the CO2 competitive adsorption on the mesoporous TiO2-SiO2 composite surface via a simple solvothermal method. After the hydrophobic modification, the CO2 photoreduction for the selective generation of CH4 over the noble-metal-free TiO2 SiO2 composite can be greatly enhanced (2.42 vs 0.10 MUmol/g in 4h). The enhanced CO2 photoreduction efficiency is assigned to the rational hydrophobic modification on TiO2-SiO2 surface by replacing Si-OH to hydrophobic Si-F bonds, which will improve the CO2 competitive adsorption and trigger the eight-electron CO2 photoreduction on the reaction kinetics. PMID- 27415145 TI - Gold-alkynyls in catalysis: alkyne activation, gold cumulenes and nuclearity. AB - The use of cationic gold(i) species in the activation of substrates containing C[triple bond, length as m-dash]C bonds has become a valuable tool for synthetic chemists. Despite the seemingly simple label of 'alkyne activation', numerous patterns of reactivity and product structure are observed in systems employing related substrates and catalysts. The complications of mechanistic determination are compounded as the number of implicated gold(i) centres involved in catalysis increases and debate about the bonding in proposed intermediates clouds the number and importance of potential reaction pathways. This perspective aims to illustrate some of the principles underpinning gold-alkynyl interactions whilst highlighting some of the contentious areas in the field and offering some insight into other, often ignored, mechanistic possibilities based on recent findings. PMID- 27415143 TI - Synthesis, Characterization, and Cross-Linking Strategy of a Quercetin-Based Epoxidized Monomer as a Naturally-Derived Replacement for BPA in Epoxy Resins. AB - The natural polyphenolic compound quercetin was functionalized and cross-linked to afford a robust epoxy network. Quercetin was selectively methylated and functionalized with glycidyl ether moieties using a microwave-assisted reaction on a gram scale to afford the desired monomer (Q). This quercetin-derived monomer was treated with nadic methyl anhydride (NMA) to obtain a cross-linked network (Q NMA). The thermal and mechanical properties of this naturally derived network were compared to those of a conventional diglycidyl ether bisphenol A-derived counterpart (DGEBA-NMA). Q-NMA had similar thermal properties [i.e., glass transition (Tg ) and decomposition (Td ) temperatures] and comparable mechanical properties (i.e., Young's Modulus, storage modulus) to that of DGEBA-NMA. However, it had a lower tensile strength and higher flexural modulus at elevated temperatures. The application of naturally derived, sustainable compounds for the replacement of commercially available petrochemical-based epoxies is of great interest to reduce the environmental impact of these materials. Q-NMA is an attractive candidate for the replacement of bisphenol A-based epoxies in various specialty engineering applications. PMID- 27415146 TI - Mechanochemical Cycloreversion of Cyclobutane Observed at the Single Molecule Level. AB - Mechanochemical cycloreversion of cyclobutane is known from ultrasound experiments. It is, however, not clear which forces are required to induce the cycloreversion. In atomic force microscopy (AFM) experiments, on the other hand, it is notoriously difficult to assign the ruptured bond. We have solved this problem through the synthesis of tailored macrocycles, in which the cyclobutane mechanophore is bypassed by an ethylene glycol chain of specific length. This macrocycle is covalently anchored between a glass substrate and an AFM cantilever by polyethylene glycol linkers. Upon mechanical stretching of the macrocycle, cycloreversion occurs, which is identified by a defined length increase of the stretched polymer. The measured length change agrees with the value calculated with the external force explicitly included (EFEI) method. By using two different lengths for the ethylene glycol safety line, the assignment becomes unambiguous. Mechanochemical cycloreversion of cyclobutane is observed at forces above 1.7 nN. PMID- 27415147 TI - Effects of Protein Malnutrition on Vigilance States and their Circadian Rhythms in 30-Day-Old Rats Submitted Total Sleep Deprivation. AB - This study examined how chronic protein malnutrition (6% casein diet) affected the electrocorticogram (ECoG) in young rats following 24 h of sleep deprivation. Baseline (basal day) ECoG-polygraphic recordings were obtained in Sprague-Dawley rats after which animals were sleep-deprived for 24 h by means of a slowly rotating cylinder. ECoG recordings were subsequently obtained for a further three days of recovery. Body weight was significantly reduced in malnourished rats from postnatal day 4 until 34. On basal day, malnourished rats showed a significant increase of slow wave sleep (SWS) during the light and dark phases of the circadian period, and over the 24 h of recording in comparison to control rats. Also, rapid eye movement sleep (REMS) was significantly increased in these rats during the 12-h dark phase of basal day, but wake ECoG activity was significantly reduced during both light and dark phases and over the 24 h of recording, as a result of sleep increases. After sleep deprivation, young malnourished rats failed to show any significant SWS rebound and, unlike control rats, they did not regain pre-deprivation SWS levels within the 3-day post-deprivation recovery period. Further, malnourished rats also failed to have a significant REMS rebound, especially during the dark phase. These results show an important alteration produced by protein malnutrition in the homeostatic and circadian control of vigilance states before and after sleep deprivation. PMID- 27415148 TI - Evaluation of the Nutritional Status in Institutionalized Children and its Relationship to the Development of Epilepsy. AB - Malnutrition as defined by the World Health Organization (WHO) in 1973 is an association of pathologic conditions caused by a lack of calories or protein intake in variable proportions. It is still one of the leading causes of infant mortality in developing countries. Risk factors for early malnutrition are absence of perinatal care and low birth weight. Epilepsy is also a very prevalent condition in childhood. A relationship between malnutrition and epilepsy has been suggested in many basic studies but it has never been proven in humans. In order to verify if malnutrition can lead to epilepsy, we reviewed anthropometric and medical files from infants in a governmental institution and tried to relate to an outcome of epilepsy. We defined malnutrition as height/weight below two pattern deviations from the NCHS tables. Two hundred and forty three children were included, 101 with malnutrition and 133 nourished. Our results indicate a predominance of malnutrition in girls (49%) and a comorbidity of malnutrition and neurological disorders. Although there were more cases of epilepsy in the malnourished group, the difference was not significant, and we could not assume that malnutrition was the cause of epilepsy in these cases because of the association of many other diseases that could also damage the central nervous system. PMID- 27415149 TI - Hormones in Foods: Presence of Enterostatin-Like Immunoreactivities in Bovine Milk. AB - Enterostatins, pentapeptides (Val-Pro-Asp-Pro-Arg [VPDPR], Val-Pro-Gly-Pro-Arg, Ala-Pro-Gly-Pro- Arg [APGPR], and others) derived from the amino terminus of procolipase, are endogenous to a variety of tissues and body fluids including brain, gut, blood, cerebrospinal fluid, and urine. The administration of exogenous peptides has been shown to elicit a variety of biologic activities, including a decrease in dietary fat preference and pancreatic insulin secretion. Since milk is a rich source of a variety of bioactive substances, especially peptides, we investigated the presence of enterostatin-like immunoreactivity in bovine milk. We measured enterostatins-APGPR and VPDPR-in milk from a herd of 19 cows randomly selected from the Louisiana State University Department of Dairy Science Research Herd in Baton Rouge; the results of this study show a mean peptide concentration in raw milk of 33.7 +/- 2.9 ng/ml for APGPR and of 104.5 +/ 16.3 ng/ml for VPDPR. A further chromatographic characterization of the nature of APGPR- and VPDPR-like immunoreactivities suggested the endogenous peptides share a common epitope with APGPR or VPDPR but are not APGPR or VPDPR. Unlike APGPR or VPDPR, the endogenous peptides were heat-labile and therefore their values were much lower in pasteurized milk. PMID- 27415150 TI - The Effect of Centrally Administered Glibenclamide, Tolbutamide and Diazoxide on Feeding in Rats. AB - While there are many theories on the control of feeding behavior that emphasize a role for energy substrates and their metabolism, the mechanism that couples changes in energy substrate supply and metabolism to alterations in food intake remains unclear. The purpose of the present project was to investigate the possibility that central ATP-sensitive potassium (KATP(+)) channels may serve as integrators between cellular energetics and alterations in neuronal activity that control feeding, such that pharmacologic manipulation of the channels would result in alterations in feeding behavior. Intracerebroventricular (ICV) injections of the KATP(+) channel blocker glibenclamide significantly increased feeding in fasted and fed male Sprague-Dawley rats. Likewise, the first generation sulfonylurea, tolbutamide, also increased feeding. ICV injection of the KATP(+) channel opener, diazoxide, modestly inhibited feeding. These results suggest that central KATP(+) channels may be involved in the regulation of feeding behavior. PMID- 27415151 TI - Imbalance of Individual Plasma Amino acids Relative to Valine and Taurine as Potential Markers of Childhood Malnutrition. AB - In the present study a typical plasma amino acid profile for a defined population of healthy Venezuelan children was established and, further, the possibility was examined that deviations from such normalized amino acid patterns can be of use to warn of an impending nutritional deficiency, caused, in part, by adverse socio economic conditions. This study comprised 152 children of both sexes ranging in age from 1 to 6 years. Classification into different socio-economic strata, ranging from impoverished to privileged, was evaluated by Graffar's method, as previously adapted by Mendez Castellano for Venezuela. The results of clinical and anthropometric examinations were used to group these children into 5 classes of nutritional sufficiency, ranging from adequate nutrition to severe undemutrition. The present data indicate that deviations in the plasma amino acid concentration profile, standardized for a defined population, can be used in combination with clinical evaluations to determine the type as well as the severity of inadequate nutrition. Abnormal ratios of several individual amino acids relative to Val and Tau may serve as early signs of (impending) undemutrition or malnutrition in children; the amino acid changes are detectable even in groups of children without any clinical signs but where sociological circumstances suggest a possibility of inadequate nutrition. Other uses for such plasma amino acid profiles may be to distinguish whether the detected amino acid abnormalities are of dietary or genetic origin, provided that the selected groups or individuals studied derive from a population with more or less the same genetic homogeneity and similar dietary customs. PMID- 27415152 TI - Postnatal Deficiencies of Zinc and Taurine Alter Electroretinograms, Oscillatory Potentials and Morphology of the Rat Retina. AB - The study objective was to evaluate the retinal response to deficiencies of zinc and taurine present throughout the period of postnatal retinal development. At parturition, Sprague-Dawley dams were assigned to one of four treatments in a 2 * 2 factorial design with two levels of zinc (4.5 and 50 MUg/g) and two levels of taurine (0 and 2 MUmol/g). Guanidinoethyl sulfonate, a taurine transport inhibitor, was added to the drinking water of the rats receiving 0 MUmol/g taurine. Male pups (n = 10) were weaned on to their respective diets at postnatal day 22. Dark adapted electroretinograms and oscillatory potentials (OP) were recorded in the pups at 48-57 days of age. At maximal light intensity, the amplitudes of the a- and b-waves were depressed by deficiency of either nutrient, but the influence of combining these treatments was less than additive; the same pattern was evident for Vmax, the maximum amplitude obtained when the b-wave was plotted as a function of light intensity. This type of interaction was also evident for the amplitudes of OP1, OP3 and OP4. Zinc deficiency independently decreased the amplitude and increased the latency of OP5, and increased the latencies of OP3 and OP4. Light and transmitting electron microscopic examination revealed the most pronounced retinal degeneration in the rats deficient in both zinc and taurine. Tibia zinc and liver taurine concentrations provide evidence that these nutrients also interact in other tissues. The findings of this study demonstrate retinal damage with deficiencies of zinc and taurine during postnatal life. These nutrients interact in at least some of their functions in the retina through an as yet unidentified mechanism. PMID- 27415153 TI - Intervention study shows suboptimal growth among children receiving a food supplement for five months in a slum in Bangladesh. AB - AIM: This study assessed weight and height changes among underweight children who received a locally produced, cereal-based, ready-to-use supplementary food. METHODS: We recruited 500 underweight Bangladeshi children aged 6-23 months from a Dhaka slum and individually matched them by sex and neighbourhood with 480 well nourished controls. The intervention group received the daily food supplement for five months, and both groups received daily micronutrient supplements. Their weight, height, mid-upper-arm circumference and head circumference were measured monthly. RESULTS: The children's mean daily weight gain decreased from 1.27 to 0.66 grams per kilogram per day (g/kg/day) in the intervention group and 0.77 to 0.49 g/kg/day in the controls after adjusting for age differences between the two groups from baseline to five months of follow-up. The mean monthly height gain decreased from 1.13 to 1.03 millimetres per metre per month in the intervention children and 1.26 to 1.01 in the controls. The weight gain was highest in the intervention children who were most wasted at baseline and the controls who were least stunted. CONCLUSION: The children showed suboptimal growth despite food supplements, highlighting the need for ongoing research to develop inexpensive, locally sourced food supplements to improve the nutrition of underweight children in Bangladesh. PMID- 27415154 TI - A Case Series on the Effects of Kripalu Yoga for Generalized Anxiety Disorder. AB - Generalized anxiety disorder (GAD) is a prevalent psychiatric disorder associated with substantial impairment and poor treatment response. Yoga influences processes that are linked to the maintenance of GAD including mindfulness, anxiety, and heart rate variability, but has yet to be evaluated among people with the disorder. The present study is a first step toward documenting the efficacy of yoga for reducing worry among people with GAD using a single-subject AB design case series and daily ratings of worry. Standardized self-report measures of worry, trait anxiety, experiential avoidance, mindfulness, and heart rate variability were assessed pre- and post-intervention. Three participants with primary GAD received eight twice-weekly Kripalu yoga sessions following a baseline data collection period. All participants showed systematic improvement in daily worry ratings on at least one index and all scores on self-reported measures of worry, anxiety, experiential avoidance, and mindfulness changed in the expected direction following yoga (with one or two exceptions). Participants also showed improved heart rate variability during a worry period from pre- to post-intervention. Yoga has the potential to improve the processes linked to GAD and should stimulate further research in this area. PMID- 27415156 TI - Fecal calprotectin for the prediction of small-bowel Crohn's disease by capsule endoscopy: a systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Fecal calprotectin is a well-established marker of mucosal inflammation. Although the correlation of elevated calprotectin levels with colonic inflammation has been confirmed repeatedly, it is less established for the small bowel. The aim of the current study was to assess the diagnostic accuracy of calprotectin for the prediction of active small-bowel disease on capsule endoscopy by performing a diagnostic test meta-analysis. MATERIALS AND METHODS: A comprehensive search was performed using PubMed/Embase. Studies addressing patients with suspected/established Crohn's disease (CD) evaluated with calprotectin and videocapsule were included. A diagnostic meta-analysis was carried out; pooled diagnostic sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each cut-off. RESULTS: Seven studies (463 patients) were entered into the final analysis. The DOR was significant for all the evaluated FC cut-offs (50 MUg/g: sensitivity 0.83, specificity 0.53, DOR 5.64; 100 MUg/g: sensitivity 0.68, specificity 0.71, DOR-5.01; 200 MUg/g: sensitivity 0.42, specificity 0.94, DOR-13.64). On sensitivity analyses, when only studies addressing suspected Crohn's or retrospective studies were included, the results did not change significantly. For studies including patients with suspected CD only, the overall accuracy for FC cut-off 50 MUg/g was further increased (sensitivity 0.89, specificity 0.55, DOR-10.3), with a negative predictive value of 91.8%. SUMMARY AND CONCLUSION: Fecal calprotectin has a significant diagnostic accuracy for the detection of small-bowel CD. Our results suggest that in patients with suspected CD with calprotectin <50 MUg/g, the likelihood of positive diagnosis is very low. PMID- 27415155 TI - Diagnostic application of next-generation sequencing in ZMYM2-FGFR1 8p11 myeloproliferative syndrome: A case report. AB - The 8p11 myeloproliferative syndrome (EMS), also known as 8p11 myeloproliferative neoplasm (8p11 MPN), is a collection of rare hematologic malignancies that are associated with fusion genes involving the tyrosine kinase receptor gene FGFR1 in chromosome 8p11. The entity is an aggressive disease with a high rate of transformation to acute myeloid leukemia (AML) and pathologically characterized by its associated eosinophilia. In this study, we reported a distinctive EMS case featuring an in-frame ZMYM2-FGFR1 fusion gene identified by next-generation sequencing technology (NGS). This patient exhibited not only typical EMS signs including elevated white blood cells in peripheral blood and hypercellular bone marrow with marked leukocytosis, but also exceptional characteristics including erythrocytosis in blood and bone marrow basophilia. Moreover, we detected 2 novel genomic mutations in 2 known leukemogenic genes, IKZF1 and ASXL1. Whether these 2 mutations play a part in EMS pathogenesis or contribute to its specific presentations clinically remain to be determined. In summary, we present a unique EMS case involving a ZMYM2-FGFR1 fusion with distinctive hematologic characteristics. PMID- 27415157 TI - Changes in the response to treatment against chronic hepatitis C between 1999 and 2015: data from a prospective cohort. AB - BACKGROUND: The drug options and strategies for treatment against hepatitis C virus (HCV) infection have changed considerably in the last few years. The aim of this study was to compare the changes in the proportion of nonresponders and patients who achieved a sustained virologic response (SVR) from 1999 to 2015 in one single cohort. PATIENTS AND METHODS: A total of 522 patients treated against chronic hepatitis C were included prospectively. The time periods were 1999-2002 [interferon (IFN)/ribavirin (RBV)], 2002-2009 (pegylated-IFN/RBV), 2010-2011 (use of IL28B genotype), 2012-2014 (pegylated-IFN/RBV/direct-acting antivirals) and 2015 (IFN-free direct-acting antiviral-based therapy). RESULTS: The numbers of nonresponders in the study periods in chronological order were as follows: 14 (40%), 76 (21.3%), 7 (8%), 10 (13%), and 0; P=1.1*10 and r=0.837. The corresponding numbers of patients who achieved SVR were 9 (25.7%), 14 (40.9%), 44 (50.6%), 51 (66.2%), and 64 (90.1%), P=3.3*10 and r=0.997. Characteristics that may impair SVR, such as advanced fibrosis, genotype 1 infection, HIV coinfection, or treatment experience, did not decrease in the last time periods. CONCLUSION: The proportion of nonresponders was significantly reduced using the IL28B genotype as a predictive tool and direct-acting antivirals further improved treatment outcome. Concomitantly, the rates of SVR showed a linear increase. PMID- 27415158 TI - Lipolysis stimulating peptides of potato protein hydrolysate effectively suppresses high-fat-diet-induced hepatocyte apoptosis and fibrosis in aging rats. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common outcomes of obesity and is characterized by the accumulation of triglycerides, increased tissue apoptosis, and fibrosis. NAFLD is more common among elderly than in younger age groups, and it causes serious hepatic complications. OBJECTIVE: In this study, alcalase treatment derived potato protein hydrolysate (APPH) with lipolysis-stimulating property has been evaluated for its efficiency to provide hepato-protection in a high-fat-diet (HFD)-fed aging rats. DESIGN: Twenty-four month-old SD rats were randomly divided into six groups (n=8): aged rats fed with standard chow, HFD-induced aged obese rats, HFD with low-dose (15 mg/kg/day) APPH treatment, HFD with moderate (45 mg/kg/day) APPH treatment, HFD with high (75 mg/kg/day) APPH treatment, and HFD with probucol. RESULTS: APPH was found to reduce the NAFLD-related effects in rat livers induced by HFD and all of the HFD fed rats exhibited heavier body weight than those with control chow diet. However, the HFD-induced hepatic fat accumulation was effectively attenuated in rats administered with low (15 mg/kg/day), moderate (45 mg/kg/day), and high (75 mg/kg/day) doses of APPH. APPH oral administration also suppressed the hepatic apoptosis- and fibrosis-related proteins induced by HFD. CONCLUSIONS: Our results thus indicate that APPH potentially attenuates hepatic lipid accumulation and anti-apoptosis and fibrosis effects in HFD-induced rats. APPH may have therapeutic potential in the amelioration of NAFLD liver damage. PMID- 27415160 TI - Published Articles on Surgical Techniques: Are They Set in Stone? PMID- 27415161 TI - Arthroscopic Classification of the Lesions of the Dorsal Capsulo-Scapholunate Septum (DCSS) of the Wrist. AB - The dorsal capsulo-scapholunate septum (DCSS) is an anatomic structure linking the scapholunate ligament and the dorsal capsule of the wrist. It should be a predynamic scapholunate stabilizer. The authors, using their experience for the extrinsic ligaments testing, suggest an arthroscopic testing of the DCSS. The status could be graded in 4 stages according to the trampoline aspect and to the fiber attachment. They report a preliminary study on a series of 53 arthroscopies made between January 2014 and December 2015 with evaluation of scapholunate ligament instability and DCSS laxity. There is a significant correlation between the lesional stage of the DCSS and the arthroscopic predynamic scapholunate instability stage (P<0.01). PMID- 27415159 TI - Zolfino landrace (Phaseolus vulgaris L.) from Pratomagno: general and specific features of a functional food. AB - BACKGROUND: The Zolfino bean is a variety of Phaseolus vulgaris, which is cultivated in a limited area of Tuscany, Italy, and is widely appreciated for its flavor and culinary uses. OBJECTIVES: A yellow Zolfino landrace cultivated in the Leccio-Reggello area was characterized and compared with three other varieties of Phaseolus vulgaris (i.e. the Borlotto, Cannellino, and Corona beans) in terms of its general features and potential as an antioxidant/anti-inflammatory agent. DESIGN: The length, width, thickness, equatorial section surface, weight, volume, and seed coat section were measured in all the beans. The seed surface area was also estimated by an original empirical method. The ability of the different beans to interfere with the enzymes of the polyol pathway (that is, aldose reductase (AR) and sorbitol dehydrogenase) was tested using the supernatant after soaking the beans at room temperature and after thermal treatment, which simulated the bean-cooking process in a controlled fashion. RESULTS: Concerning the general features, Zolfino was comparable with other beans, except Corona, in terms of surface-volume ratio, which possesses the lowest tegument thickness. Moreover, Zolfino appears the most effective in inhibiting AR activity. The inhibitory ability is unaffected by thermal treatment and appears to be associated with compound(s) present in the coat of the bean. CONCLUSIONS: The ability of Zolfino to inhibit AR, thus reducing the flux of glucose through the polyol pathway, highlights the features of Zolfino as a functional food, potentially useful in treating the dysfunctions linked to the hyperactivity of AR, such as diabetic complications or inflammatory responses. PMID- 27415164 TI - QuikQuiz. PMID- 27415162 TI - Joining Peter the Great's Navy. PMID- 27415165 TI - Pearls. AB - 'Pearls' enables sports medicine professionals to share the practical tips they've developed through treating active patients. We invite you to send your contributions to Pearls Editor, The Physician and Sportsmedicine, 4530 W 77th St, Minneapolis, MN 55435. Illustrations or photos are encouraged. Selected pearls will be published, accompanied by the author's name. PMID- 27415167 TI - Nibbling. PMID- 27415166 TI - Coming in Sportsmedicine. PMID- 27415168 TI - Helping frail, older adults build strength. PMID- 27415169 TI - Rehab helps Dennis Byrd soar. PMID- 27415170 TI - Bouncing Back From Hip Pain. PMID- 27415171 TI - Forum. AB - A Forum for Our Readers Forum provides an opportunity for our readers to comment on the articles that we publish. Illustrative figures are welcome. Address correspondence to Forum, The Physician and Sportsmedicine, 4530 W 77th St, Minneapolis, MN 55435. PMID- 27415172 TI - Injuries in Equestrian Sports. AB - In brief The authors surveyed equestrians to determine an injury profile. Based on responses from 2,195 frequent riders, the study confirms previous findings regarding injury rates, injury sites, and helmet use. New findings include a large number of neck and back injuries and a likelihood of injured riders to be between 15 and 44 years of age, ride English style, and have less than 10 years of riding experience. Data also show that many horseback-riding injuries are treated in physicians' offices. The high percentage of injured patients who suffered prolonged disability underscores the need for physicians to counsel horseback-riding patients about hazards and safety measures-especially helmet use. PMID- 27415173 TI - HIV-Positive Athletes. AB - In brief Though the risk of HIV transmission in sports' is slight, physicians who treat active patients can encounter some weighty legal issues. Mandatory testing, exclusion of HIV-positive athletes from competition, and breaching of patient confidentiality are actions that can lead to lawsuits. Knowing the possible consequences can help physicians in setting effective-and legal-prevention policies. PMID- 27415174 TI - Differentiating Stress Fracture From Periostitis. AB - In brief Even in the age of high-technology MRI and CT, the triple-phase bone scan (TPBS) remains an exceptionally useful and accurate tool in evaluating athletic injuries. This is perhaps best seen in active people with overuse injuries of the tibia, femur, or humerus when plain films are negative but bone pain persists. Differentiating periostitis from stress fracture requires analyzing distinctive TPBS appearances and patterns. PMID- 27415175 TI - Circadian Rhythms. AB - In brief Active people watch their body clocks for health and performance advantages. Recent research on circadian rhythms suggests that exercising in the morning is safe, exercise at any time of day boosts mood, athletic performance peaks late in the day, athletes should train at the same time they will race, and jet lag may influence team sports. PMID- 27415176 TI - Immediate Diagnosis of Ankle Trauma. AB - In brief Traumatic Injuries to the ankle vary greatly in severity, from minor contusions to displaced intra-articular fractures. A systematic approach to their evaluation can lead to more accurate diagnoses and help simplify treatment options. Primary care physicians can successfully manage most sports-related ankle trauma, but knowing when to obtain orthopedic consultation is equally important. PMID- 27415177 TI - Intramuscular Abscess. AB - In brief A 24-year-old man had been reusing needles to inject anabolic-androgenic steroids intramuscularly and developed a thigh abscess. He was treated with intravenous antibiotics, and the abscess was surgically drained. The case highlights the danger of intramuscular steroid injection and of reusing needles. PMID- 27415178 TI - Staying Fit as You Age. PMID- 27415181 TI - The Effectiveness of Low-Level Laser Therapy in Patients with Drug-Induced Hyposalivation: A Pilot Study. AB - OBJECTIVE: The aim of this study was to compare switched on and switched off (sham) low-level laser therapy (LLLT) in the treatment of drug-induced hyposalivation. BACKGROUND DATA: Hyposalivation is decreased salivary flow rate most frequently present in patients who take a lot of medication, suffer from Sjogren's syndrome, or were irradiated. Available therapies provide only short term relief. MATERIALS AND METHODS: Forty-three participants (40 females and 3 males, average age 72.3 +/- 8.9) participated in the study. Before therapy or after therapy, every participant fulfilled quality-of-life assessment scale (OHIP CRO14). Unstimulated and stimulated salivary flow rates were measured before and after treatment. The LLLT was performed by the use of gallium-aluminum-arsenide (GaAlAs) laser (830 nm) on parotid, submandibular, and sublingual glands every day except during weekends for 14 days. RESULTS: Significant difference in unstimulated salivary flow rate after the treatment was found in the study group (p = 0.002) compared with the sham group. No significant difference in stimulated salivary flow rate after treatment was found in the laser group (p = 0.626) nor in the sham laser group (p = 0.233). No significant difference in patient's quality-of-life score was found after both treatments. CONCLUSIONS: The results of this study showed that the LLLT increased unstimulated salivary flow rate significantly. However, stimulated salivary flow rate did not increase significantly after the LLLT. In patients who underwent sham laser therapy, neither unstimulated nor stimulated salivary flow rate increased significantly. PMID- 27415180 TI - Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS. AB - OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a "reverse" round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n = 150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p < 0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 +/- 19.1%. We calculated a diagnostic cut-off of >568.5 pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work up. PMID- 27415182 TI - Transplantation of a bacterial consortium ameliorates trinitrobenzenesulfonic acid-induced colitis and intestinal dysbiosis in rats. AB - AIM: To investigate the effects of a defined bacterial consortium on trinitrobenzenesulfonic acid (TNBS)-induced colitis and intestinal dysbiosis in rats. MATERIALS & METHODS: Rats with TNBS-induced colitis were treated with ceftriaxone and/or a mixture of ten bacterial strains isolated from mouse feces for continuous 24 days. Macroscopic and histopathological parameters in colonic tissue were compared, as were myeloperoxidase enzyme activity and cytokine levels. Patterns of intestinal microbiota were assessed by PCR-denaturing gradient gel electrophoresis, the abundance of selected microbial groups was evaluated by qPCR. RESULTS & CONCLUSION: Transplantation of the bacterial consortium showed anti-inflammatory activity in the intestines of rats with TNBS induced colitis and contributed to the rapid re-establishment of intestinal microbial equilibrium. A defined bacterial consortium may be a viable therapeutic option for the treatment inflammatory bowel disease. PMID- 27415183 TI - Silylaryl Halides Can Replace Triflates as Aryne Precursors. AB - Silylaryl bromides and iodides can be prepared in one step from commercially available starting materials. Arynes can be generated from these compounds under conditions nearly identical to those employed for silylaryl triflates. Three distinct transformations, ortho-arylation of N-tritylanilines, intermolecular addition of arynes to amides, and reaction of ureas with arynes, were shown to be successful for the new aryne precursors. The main advantage of silylaryl halides relative to silyl aryl triflates is their one-step preparation from commercially available starting materials. PMID- 27415184 TI - High proportions of older people with normal nutritional status have poor protein intake and low diet quality. AB - INTRODUCTION: The Mini Nutritional Assessment (MNA) is a well-validated instrument examining the nutritional status of older people. The aim of this study was to examine how older people's energy and nutrient intakes are associated with the MNA and to determine how sensitive and specific MNA is in identifying those having low energy and protein intakes. MATERIALS AND METHODS: This cross-sectional study combined data from five nutritional studies (N=900): both home-dwelling and institutionalized older people without and with disabilities. Their nutritional status was assessed with MNA, and nutrient intakes were retrieved from 1 to 3day food diaries. Nutrient intakes were divided according to MNA status (normal nutritional status, at-risk of malnutrition, malnourished). Sensitivity, specificity, and likelihood ratios of MNA of various cut-off points were tested with recommended protein and energy intakes. ROC curves was constructed. RESULTS: Energy, protein and most nutrient intakes showed logical linear trends according to MNA classes. However, more than three-fourths of the participants with MNA>23.5 had lower than recommended protein intakes. Sensitivity of MNA ranged from 0.32 to 0.82 for recommended energy (F:1570kcal/d/M:2070kcal/d) and protein intakes (1.0g/kg BW or 1.2g/kgBW) cut-off points, and specificity from 0.75 to 0.25, respectively. AUC values were low (0.52-0.53). CONCLUSIONS: MNA status was consistently associated with nutrient intakes and diet quality. However, a high proportion of older people even with normal nutritional status had poor energy and protein intakes. Thus, MNA does not identify all those with poor nutrient intakes who may be at risk of developing malnutrition. PMID- 27415185 TI - Searching for the Tracy-Widom distribution in nonequilibrium processes. AB - While originally discovered in the context of the Gaussian unitary ensemble, the Tracy-Widom distribution also rules the height fluctuations of growth processes. This suggests that there might be other nonequilibrium processes in which the Tracy-Widom distribution plays an important role. In our contribution we study one-dimensional systems with domain wall initial conditions. For an appropriate choice of parameters, the profile develops a rarefaction wave while maintaining the initial equilibrium states far to the left and right, which thus serve as infinitely extended thermal reservoirs. For a Fermi-Pasta-Ulam type anharmonic chain, we will demonstrate that the time-integrated current has a deterministic contribution, linear in time t, and fluctuations of size t^{1/3} with a Tracy Widom distributed random amplitude. PMID- 27415186 TI - Diffusion with stochastic resetting at power-law times. AB - What happens when a continuously evolving stochastic process is interrupted with large changes at random intervals tau distributed as a power law ~tau^{ (1+alpha)};alpha>0? Modeling the stochastic process by diffusion and the large changes as abrupt resets to the initial condition, we obtain exact closed-form expressions for both static and dynamic quantities, while accounting for strong correlations implied by a power law. Our results show that the resulting dynamics exhibits a spectrum of rich long-time behavior, from an ever-spreading spatial distribution for alpha<1, to one that is time independent for alpha>1. The dynamics has strong consequences on the time to reach a distant target for the first time; we specifically show that there exists an optimal alpha that minimizes the mean time to reach the target, thereby offering a step towards a viable strategy to locate targets in a crowded environment. PMID- 27415187 TI - General continuum approach for dissipative systems of repulsive particles. AB - We propose a general coarse-graining method to derive a continuity equation that describes any dissipative system of repulsive particles interacting through short ranged potentials. In our approach, the effect of particle-particle correlations is incorporated to the overall balance of energy, and a nonlinear diffusion equation is obtained to represent the overdamped dynamics. In particular, when the repulsive interaction potential is a short-ranged power law, our approach reveals a distinctive correspondence between particle-particle energy and the generalized thermostatistics of Tsallis for any nonpositive value of the entropic index q. Our methodology can also be applied to microscopic models of superconducting vortices and complex plasma, where particle-particle correlations are pronounced at low concentrations. The resulting continuum descriptions provide elucidating and useful insights on the microdynamical behavior of these physical systems. The consistency of our approach is demonstrated by comparison with molecular dynamics simulations. PMID- 27415188 TI - One-parameter class of uncertainty relations based on entropy power. AB - We use the concept of entropy power to derive a one-parameter class of information-theoretic uncertainty relations for pairs of conjugate observables in an infinite-dimensional Hilbert space. This class constitutes an infinite tower of higher-order statistics uncertainty relations, which allows one in principle to determine the shape of the underlying information-distribution function by measuring the relevant entropy powers. We illustrate the capability of this class by discussing two examples: superpositions of vacuum and squeezed states and the Cauchy-type heavy-tailed wave function. PMID- 27415189 TI - Field-induced superdiffusion and dynamical heterogeneity. AB - By analyzing two kinetically constrained models of supercooled liquids we show that the anomalous transport of a driven tracer observed in supercooled liquids is another facet of the phenomenon of dynamical heterogeneity. We focus on the Fredrickson-Andersen and the Bertin-Bouchaud-Lequeux models. By numerical simulations and analytical arguments we demonstrate that the violation of the Stokes-Einstein relation and the field-induced superdiffusion observed during a long preasymptotic regime have the same physical origin: while a fraction of probes do not move, others jump repeatedly because they are close to local mobile regions. The anomalous fluctuations observed out of equilibrium in the presence of a pulling force epsilon,sigma_{x}^{2}(t)= ^{2}~t^{3/2}, which are accompanied by the asymptotic decay alpha_{epsilon}(t)~t^{-1/2} of the non-Gaussian parameter from nontrivial values to zero, are due to the splitting of the probes population in the two (mobile and immobile) groups and to dynamical correlations, a mechanism expected to happen generically in supercooled liquids. PMID- 27415190 TI - Compressive sensing reconstruction of feed-forward connectivity in pulse-coupled nonlinear networks. AB - Utilizing the sparsity ubiquitous in real-world network connectivity, we develop a theoretical framework for efficiently reconstructing sparse feed-forward connections in a pulse-coupled nonlinear network through its output activities. Using only a small ensemble of random inputs, we solve this inverse problem through the compressive sensing theory based on a hidden linear structure intrinsic to the nonlinear network dynamics. The accuracy of the reconstruction is further verified by the fact that complex inputs can be well recovered using the reconstructed connectivity. We expect this Rapid Communication provides a new perspective for understanding the structure-function relationship as well as compressive sensing principle in nonlinear network dynamics. PMID- 27415191 TI - Stable and unstable development of an interfacial sliding instability. AB - Examining a nonlinear instability of sliding rate on a frictional interface of elastic bodies, we investigate whether laboratory-constrained frictional relations suggest universal scaling under even the simplest of configurations. We find blowup solutions by solving an equivalent, classical problem in fracture mechanics. The solutions are fixed points of a dynamical system and we show that their stability is lost by a cascade of Hopf bifurcations as a single problem parameter is increased, leading to chaotic dynamics. PMID- 27415192 TI - Barrier-induced chaos in a kicked rotor: Classical subdiffusion and quantum localization. AB - The relation between classically chaotic dynamics and quantum localization is studied in a system that violates the assumptions of the Kolmogorov-Arnold-Moser (KAM) theorem, namely, the kicked rotor in a discontinuous potential barrier. We show that the discontinuous barrier induces chaos and more than two distinct subdiffusive energy growth regimes, the latter being an unusual feature for Hamiltonian chaos. We show that the dynamical localization in the quantized version of this system carries the imprint of non-KAM classical dynamics through the dependence of quantum break time on subdiffusion exponents. We briefly comment on the experimental feasibility of this system. PMID- 27415193 TI - Linear readout of object manifolds. AB - Objects are represented in sensory systems by continuous manifolds due to sensitivity of neuronal responses to changes in physical features such as location, orientation, and intensity. What makes certain sensory representations better suited for invariant decoding of objects by downstream networks? We present a theory that characterizes the ability of a linear readout network, the perceptron, to classify objects from variable neural responses. We show how the readout perceptron capacity depends on the dimensionality, size, and shape of the object manifolds in its input neural representation. PMID- 27415195 TI - Determining the interparticle force laws in amorphous solids from a visual image. AB - We consider the problem of how to determine the force laws in an amorphous system of interacting particles. Given the positions of the centers of mass of the constituent particles we propose an algorithm to determine the interparticle force laws. Having n different types of constituents we determine the coefficients in the Laurent polynomials for the n(n+1)/2 possibly different force laws. A visual providing the particle positions in addition to a measurement of the pressure is all that is required. The algorithm proposed includes a part that can correct for experimental errors in the positions of the particles. Such a correction of unavoidable measurement errors is expected to benefit many experiments in the field. PMID- 27415194 TI - Pseudo-one-dimensional nucleation in dilute polymer solutions. AB - Pathogenic protein fibrils have been shown in vitro to have nucleation-dependent kinetics despite the fact that one-dimensional structures do not have the size dependent surface energy responsible for the lag time in classical theory. We present a theory showing that the conformational entropy of the peptide chains creates a free-energy barrier that is analogous to the translational entropy barrier in higher dimensions. We find that the dynamics of polymer rearrangement make it very unlikely for nucleation to succeed along the lowest free-energy trajectory, meaning that most of the nucleation flux avoids the free-energy saddle point. We use these results to construct a three-dimensional model for amyloid nucleation that accounts for conformational entropy, backbone H bonds, and side-chain interactions to compute nucleation rates as a function of concentration. PMID- 27415196 TI - Strong-field dynamo action in rapidly rotating convection with no inertia. AB - The earth's magnetic field is generated by dynamo action driven by convection in the outer core. For numerical reasons, inertial and viscous forces play an important role in geodynamo models; however, the primary dynamical balance in the earth's core is believed to be between buoyancy, Coriolis, and magnetic forces. The hope has been that by setting the Ekman number to be as small as computationally feasible, an asymptotic regime would be reached in which the correct force balance is achieved. However, recent analyses of geodynamo models suggest that the desired balance has still not yet been attained. Here we adopt a complementary approach consisting of a model of rapidly rotating convection in which inertial forces are neglected from the outset. Within this framework we are able to construct a branch of solutions in which the dynamo generates a strong magnetic field that satisfies the expected force balance. The resulting strongly magnetized convection is dramatically different from the corresponding solutions in which the field is weak. PMID- 27415197 TI - Energy cascade and its locality in compressible magnetohydrodynamic turbulence. AB - We investigate energy transfer across scales in three-dimensional compressible magnetohydrodynamic (MHD) turbulence, a model often used to study space and astrophysical plasmas. Analysis shows that kinetic and magnetic energies cascade conservatively from large to small scales in cases with varying degrees of compression. With more compression, energy fluxes due to pressure dilation and subscale mass flux are greater, but conversion between kinetic and magnetic energy by magnetic line stretching is less efficient. Energy transfer between the same fields is dominated by local contributions regardless of compressive effects. In contrast, the conversion between kinetic and internal energy by pressure dilation is dominated by the largest scale contributions. Energy conversion between the velocity and magnetic fields is weakly local. PMID- 27415198 TI - Evolution of a superfluid vortex filament tangle driven by the Gross-Pitaevskii equation. AB - The development and decay of a turbulent vortex tangle driven by the Gross Pitaevskii equation is studied. Using a recently developed accurate and robust tracking algorithm, all quantized vortices are extracted from the fields. The Vinen's decay law for the total vortex length with a coefficient that is in quantitative agreement with the values measured in helium II is observed. The topology of the tangle is then investigated showing that linked rings may appear during the evolution. The tracking also allows for determining the statistics of small-scale quantities of vortex lines, exhibiting large fluctuations of curvature and torsion. Finally, the temporal evolution of the Kelvin wave spectrum is obtained providing evidence of the development of a weak-wave turbulence cascade. PMID- 27415199 TI - Strong higher-order resonant contributions to x-ray line polarization in hot plasmas. AB - We studied angular distributions of x rays emitted in resonant recombination of highly charged iron and krypton ions, resolving dielectronic, trielectronic, and quadruelectronic channels. A tunable electron beam drove these processes, inducing x rays registered by two detectors mounted along and perpendicular to the beam axis. The measured emission asymmetries comprehensively benchmarked full order atomic calculations. We conclude that accurate polarization diagnostics of hot plasmas can only be obtained under the premise of inclusion of higher-order processes that were neglected in earlier work. PMID- 27415200 TI - Plasma dynamics near critical density inferred from direct measurements of laser hole boring. AB - We have used multiframe picosecond optical interferometry to make direct measurements of the hole boring velocity, v_{HB}, of the density cavity pushed forward by a train of CO_{2} laser pulses in a near critical density helium plasma. As the pulse train intensity rises, the increasing radiation pressure of each pulse pushes the density cavity forward and the plasma electrons are strongly heated. After the peak laser intensity, the plasma pressure exerted by the heated electrons strongly impedes the hole boring process and the v_{HB} falls rapidly as the laser pulse intensity falls at the back of the laser pulse train. A heuristic theory is presented that allows the estimation of the plasma electron temperature from the measurements of the hole boring velocity. The measured values of v_{HB}, and the estimated values of the heated electron temperature as a function of laser intensity are in reasonable agreement with those obtained from two-dimensional numerical simulations. PMID- 27415201 TI - Minimal energy ensemble Monte Carlo algorithm for the partition function of fermions coupled to classical fields. AB - Models of noninteracting fermions coupled to auxiliary classical fields are relevant to the understanding of a wide variety of problems in many-body physics, e.g., the description of manganites, diluted magnetic semiconductors, or strongly interacting electrons on lattices. We present a flat-histogram Monte Carlo algorithm that simulates a statistical ensemble that allows one to directly acquire the partition function at all temperatures for such systems. The defining feature of the algorithm is that it utilizes the complete thermodynamic information from the full energy spectrum of noninteracting fermions available during sampling of the configuration space of the classical fields. We benchmark the method for the classical Ising and Potts models in two dimensions, as well as the Falicov-Kimball model describing itinerant electrons interacting with heavy ions. PMID- 27415202 TI - Quantum quenches in the sine-Gordon model: A semiclassical approach. AB - We compute the time evolution of correlation functions after quantum quenches in the sine-Gordon model within the semiclassical approximation, which is expected to yield accurate results for small and slow quenches producing slow quasiparticles with low density. We demonstrate this by reproducing results of a recent form-factor calculation of the relaxation of expectation values [B. Bertini, D. Schuricht, and F. H. L. Essler, J. Stat. Mech. (2014) P100351742 546810.1088/1742-5468/2014/10/P10035]. Extending these results, we find that-in the universal limit of vanishingly small quasiparticle velocities-the expectation values of most vertex operators do not decay to zero. We give analytic expressions for the relaxation of dynamic correlation functions and show that they have diffusive behavior for large timelike separation. PMID- 27415203 TI - Strongly confined fluids: Diverging time scales and slowing down of equilibration. AB - The Newtonian dynamics of strongly confined fluids exhibits a rich behavior. Its confined and unconfined degrees of freedom decouple for confinement length L->0. In that case and for a slit geometry the intermediate scattering functions S_{MUnu}(q,t) simplify, resulting for (MU,nu)?(0,0) in a Knudsen-gas-like behavior of the confined degrees of freedom, and otherwise in S_{?}(q,t), describing the structural relaxation of the unconfined ones. Taking the coupling into account we prove that the energy fluctuations relax exponentially. For smooth potentials the relaxation times diverge as L^{-3} and L^{-4}, respectively, for the confined and unconfined degrees of freedom. The strength of the L^{-3} divergence can be calculated analytically. It depends on the pair potential and the two-dimensional pair distribution function. Experimental setups are suggested to test these predictions. PMID- 27415204 TI - Critical behavior of su(1|1) supersymmetric spin chains with long-range interactions. AB - We introduce a general class of su(1|1) supersymmetric spin chains with long range interactions which includes as particular cases the su(1|1) Inozemtsev (elliptic) and Haldane-Shastry chains, as well as the XX model. We show that this class of models can be fermionized with the help of the algebraic properties of the su(1|1) permutation operator and take advantage of this fact to analyze their quantum criticality when a chemical potential term is present in the Hamiltonian. We first study the low-energy excitations and the low-temperature behavior of the free energy, which coincides with that of a (1+1)-dimensional conformal field theory (CFT) with central charge c=1 when the chemical potential lies in the critical interval (0,E(pi)), E(p) being the dispersion relation. We also analyze the von Neumann and Renyi ground state entanglement entropies, showing that they exhibit the logarithmic scaling with the size of the block of spins characteristic of a one-boson (1+1)-dimensional CFT. Our results thus show that the models under study are quantum critical when the chemical potential belongs to the critical interval, with central charge c=1. From the analysis of the fermion density at zero temperature, we also conclude that there is a quantum phase transition at both ends of the critical interval. This is further confirmed by the behavior of the fermion density at finite temperature, which is studied analytically (at low temperature), as well as numerically for the su(1|1) elliptic chain. PMID- 27415205 TI - Perturbations of linear delay differential equations at the verge of instability. AB - The characteristic equation for a linear delay differential equation (DDE) has countably infinite roots on the complex plane. This paper considers linear DDEs that are on the verge of instability, i.e., a pair of roots of the characteristic equation lies on the imaginary axis of the complex plane and all other roots have negative real parts. It is shown that when small noise perturbations are present, the probability distribution of the dynamics can be approximated by the probability distribution of a certain one-dimensional stochastic differential equation (SDE) without delay. This is advantageous because equations without delay are easier to simulate and one-dimensional SDEs are analytically tractable. When the perturbations are also linear, it is shown that the stability depends on a specific complex number. The theory is applied to study oscillators with delayed feedback. Some errors in other articles that use multiscale approach are pointed out. PMID- 27415207 TI - Quantum jump model for a system with a finite-size environment. AB - Measuring the thermodynamic properties of open quantum systems poses a major challenge. A calorimetric detection has been proposed as a feasible experimental scheme to measure work and fluctuation relations in open quantum systems. However, the detection requires a finite size for the environment, which influences the system dynamics. This process cannot be modeled with the standard stochastic approaches. We develop a quantum jump model suitable for systems coupled to a finite-size environment. We use the method to study the common fluctuation relations and prove that they are satisfied. PMID- 27415206 TI - Effects of critical fluctuations and dimensionality on the jump in specific heat at the superconducting transition temperature: Application to YBa_{2}Cu_{3}O_{7 delta},Bi_{2}Sr_{2}CaCu_{2}O_{8+delta}, and KOs_{2}O_{6} compounds. AB - We report on a study of the superconducting order parameter thermodynamic fluctuations in YBa_{2}Cu_{3}O_{7-delta},Bi_{2}Sr_{2}CaCu_{2}O_{8+delta}, and KOs_{2}O_{6} compounds. A nonperturbative technique within the framework of the renormalized Gaussian approach is proposed. The essential features are reported (analytically and numerically) through Ginzburg-Landau (GL) model-based calculations which take into account both the dimension and the microscopic parameters of the system. By presenting a self-consistent approach improvement on the GL theory, a technique for obtaining corrections to the asymptotic critical behavior in terms of nonuniversal parameters is developed. Therefore, corrections to the specific heat and the critical transition temperature for one-, two-, and three-dimensional samples are found taking into account the fact that fluctuations occur at all length scales as the critical point of a system is approached. The GL model in the free-field approximation and the 3D-XY model are suitable for describing the weak and strong fluctuation regimes respectively. However, with a modified quadratic coefficient, the renormalized GL model is able to explain certain experimental observations including the specific heat of complicated systems, such as the cup-rate superconductors and the beta-pyrochlore oxides. It is clearly shown that the enhancement, suppression, or rounding of the specific heat jump of high-T_{c} cup-rate superconductors at the transition are indicative of the order parameter thermodynamic fluctuations according to the dimension and the nature of interactions. PMID- 27415208 TI - Equilibration of isolated many-body quantum systems with respect to general distinguishability measures. AB - We demonstrate equilibration of isolated many-body systems in the sense that, after initial transients have died out, the system behaves practically indistinguishable from a time-independent steady state, i.e., non-negligible deviations are unimaginably rare in time. Measuring the distinguishability in terms of quantum mechanical expectation values, results of this type have been previously established under increasingly weak assumptions about the initial disequilibrium, the many-body Hamiltonian, and the considered observables. Here, we further extend these results with respect to generalized distinguishability measures which fully take into account the fact that the actually observed, primary data are not expectation values but rather the probabilistic occurrence of different possible measurement outcomes. PMID- 27415209 TI - Quantum-classical correspondence principle for work distributions in a chaotic system. AB - We numerically study the work distributions in a chaotic system and examine the relationship between quantum work and classical work. Our numerical results suggest that there exists a correspondence principle between quantum and classical work distributions in a chaotic system. This correspondence was proved for one-dimensional integrable systems in a recent work [Jarzynski, Quan, and Rahav, Phys. Rev. X 5, 031038 (2015)1063-651X10.1103/PhysRevX.5.031038]. Our investigation further justifies the definition of quantum work via two-point energy measurements. PMID- 27415210 TI - Distributional behaviors of time-averaged observables in the Langevin equation with fluctuating diffusivity: Normal diffusion but anomalous fluctuations. AB - We consider the Langevin equation with dichotomously fluctuating diffusivity, where the diffusion coefficient changes dichotomously over time, in order to study fluctuations of time-averaged observables in temporally heterogeneous diffusion processes. We find that the time-averaged mean-square displacement (TMSD) can be represented by the occupation time of a state in the asymptotic limit of the measurement time and hence occupation time statistics is a powerful tool for calculating the TMSD in the model. We show that the TMSD increases linearly with time (normal diffusion) but the time-averaged diffusion coefficients are intrinsically random when the mean sojourn time for one of the states diverges, i.e., intrinsic nonequilibrium processes. Thus, we find that temporally heterogeneous environments provide anomalous fluctuations of time averaged diffusivity, which have relevance to large fluctuations of the diffusion coefficients obtained by single-particle-tracking trajectories in experiments. PMID- 27415212 TI - Topological similarity of random cell complexes and applications. AB - Although random cell complexes occur throughout the physical sciences, there does not appear to be a standard way to quantify their statistical similarities and differences. The various proposals in the literature are usually motivated by the analysis of particular physical systems and do not necessarily apply to general situations. The central concepts in this paper-the swatch and the cloth-provide a description of the local topology of a cell complex that is general (any physical system that can be represented as a cell complex is admissible) and complete (any statistical question about the local topology can be answered from the cloth). Furthermore, this approach allows a distance to be defined that measures the similarity of the local topology of two cell complexes. The distance is used to identify a steady state of a model grain boundary network, quantify the approach to this steady state, and show that the steady state is independent of the initial conditions. The same distance is then employed to show that the long-term properties in simulations of a specific model of a dislocation network do not depend on the implementation of dislocation intersections. PMID- 27415211 TI - Quantum phase transition, universality, and scaling behaviors in the spin-1/2 Heisenberg model with ferromagnetic and antiferromagnetic competing interactions on a honeycomb lattice. AB - The quantum phase transition, scaling behaviors, and thermodynamics in the spin 1/2 quantum Heisenberg model with antiferromagnetic coupling J>0 in the armchair direction and ferromagnetic interaction J^{'}<0 in the zigzag direction on a honeycomb lattice are systematically studied using the continuous-time quantum Monte Carlo method. By calculating the Binder ratio Q_{2} and spin stiffness rho in two directions for various coupling ratios alpha=J^{'}/J under different lattice sizes, we found that a quantum phase transition from the dimerized phase to the stripe phase occurs at the quantum critical point alpha_{c}=-0.93. Through the finite-size scaling analysis on Q_{2}, rho_{x}, and rho_{y}, we determined the critical exponent related to the correlation length nu to be 0.7212(8), implying that this transition falls into a classical Heisenberg O(3) universality. A zero magnetization plateau is observed in the dimerized phase, whose width decreases with increasing alpha. A phase diagram in the coupling ratio alpha-magnetic field h plane is obtained, where four phases, including dimerized, stripe, canted stripe, and polarized, are identified. It is also unveiled that the temperature dependence of the specific heat C(T) for different alpha's intersects precisely at one point, similar to that of liquid ^{3}He under different pressures and several magnetic compounds under various magnetic fields. The scaling behaviors of Q_{2}, rho, and C(T) are carefully analyzed. The susceptibility is compared with the experimental data to give the magnetic parameters of both compounds. PMID- 27415213 TI - Density functional formulation of the random-phase approximation for inhomogeneous fluids: Application to the Gaussian core and Coulomb particles. AB - Using the adiabatic connection, we formulate the free energy in terms of the correlation function of a fictitious system, h_{lambda}(r,r^{'}), in which interactions lambdau(r,r^{'}) are gradually switched on as lambda changes from 0 to 1. The function h_{lambda}(r,r^{'}) is then obtained from the inhomogeneous Ornstein-Zernike equation and the two equations constitute a general liquid-state framework for treating inhomogeneous fluids. The two equations do not yet constitute a closed set. In the present work we use the closure c_{lambda}(r,r^{'})~-lambdabetau(r,r^{'}), known as the random-phase approximation (RPA). We demonstrate that the RPA is identical with the variational Gaussian approximation derived within the field-theoretical framework, originally derived and used for charged particles. We apply our generalized RPA approximation to the Gaussian core model and Coulomb charges. PMID- 27415214 TI - Stepwise positional-orientational order and the multicritical-multistructural global phase diagram of the s=3/2 Ising model from renormalization-group theory. AB - The spin-3/2 Ising model, with nearest-neighbor interactions only, is the prototypical system with two different ordering species, with concentrations regulated by a chemical potential. Its global phase diagram, obtained in d=3 by renormalization-group theory in the Migdal-Kadanoff approximation or equivalently as an exact solution of a d=3 hierarchical lattice, with flows subtended by 40 different fixed points, presents a very rich structure containing eight different ordered and disordered phases, with more than 14 different types of phase diagrams in temperature and chemical potential. It exhibits phases with orientational and/or positional order. It also exhibits quintuple phase transition reentrances. Universality of critical exponents is conserved across different renormalization-group flow basins via redundant fixed points. One of the phase diagrams contains a plastic crystal sequence, with positional and orientational ordering encountered consecutively as temperature is lowered. The global phase diagram also contains double critical points, first-order and critical lines between two ordered phases, critical end points, usual and unusual (inverted) bicritical points, tricritical points, multiple tetracritical points, and zero-temperature criticality and bicriticality. The four-state Potts permutation-symmetric subspace is contained in this model. PMID- 27415215 TI - Central limit theorem for a class of globally correlated random variables. AB - The standard central limit theorem with a Gaussian attractor for the sum of independent random variables may lose its validity in the presence of strong correlations between the added random contributions. Here, we study this problem for similar interchangeable globally correlated random variables. Under these conditions, a hierarchical set of equations is derived for the conditional transition probabilities. This result allows us to define different classes of memory mechanisms that depend on a symmetric way on all involved variables. Depending on the correlation mechanisms and statistics of the single variables, the corresponding sums are characterized by distinct probability densities. For a class of urn models it is also possible to characterize their domain of attraction, which, as in the standard case, is parametrized by the probability density of each random variable. Symmetric and asymmetric q-Gaussian attractors (q<1) arise in a particular two-state case of these urn models. PMID- 27415216 TI - Finite size effects in the averaged eigenvalue density of Wigner random-sign real symmetric matrices. AB - Nowadays, strict finite size effects must be taken into account in condensed matter problems when treated through models based on lattices or graphs. On the other hand, the cases of directed bonds or links are known to be highly relevant in topics ranging from ferroelectrics to quotation networks. Combining these two points leads us to examine finite size random matrices. To obtain basic materials properties, the Green's function associated with the matrix has to be calculated. To obtain the first finite size correction, a perturbative scheme is hereby developed within the framework of the replica method. The averaged eigenvalue spectrum and the corresponding Green's function of Wigner random sign real symmetric N*N matrices to order 1/N are finally obtained analytically. Related simulation results are also presented. The agreement is excellent between the analytical formulas and finite size matrix numerical diagonalization results, confirming the correctness of the first-order finite size expression. PMID- 27415217 TI - Quantum correlated cluster mean-field theory applied to the transverse Ising model. AB - Mean-field theory (MFT) is one of the main available tools for analytical calculations entailed in investigations regarding many-body systems. Recently, there has been a surge of interest in ameliorating this kind of method, mainly with the aim of incorporating geometric and correlation properties of these systems. The correlated cluster MFT (CCMFT) is an improvement that succeeded quite well in doing that for classical spin systems. Nevertheless, even the CCMFT presents some deficiencies when applied to quantum systems. In this article, we address this issue by proposing the quantum CCMFT (QCCMFT), which, in contrast to its former approach, uses general quantum states in its self-consistent mean field equations. We apply the introduced QCCMFT to the transverse Ising model in honeycomb, square, and simple cubic lattices and obtain fairly good results both for the Curie temperature of thermal phase transition and for the critical field of quantum phase transition. Actually, our results match those obtained via exact solutions, series expansions or Monte Carlo simulations. PMID- 27415218 TI - Edge mode dynamics of quenched topological wires. AB - The fermionic and Majorana edge mode dynamics of various topological systems are compared, after a sudden global quench of the Hamiltonian parameters takes place. Attention is focused on the regimes where the survival probability of an edge state has oscillations either due to critical or off-critical quenches. The nature of the wave functions and the overlaps between the eigenstates of different points in parameter space determine the various types of behaviors, and the distinction due to the Majorana nature of the excitations plays a lesser role. Performing a sequence of quenches, it is shown that the edge states, including Majorana modes, may be switched off and on. Also, the generation of Majoranas due to quenching from a trivial phase is discussed. PMID- 27415219 TI - Dissipation in small systems: Landau-Zener approach. AB - We establish a stochastic thermodynamics for a Fermionic level driven by a time dependent force and interacting with initially thermalized levels playing the role of a reservoir. The driving induces consecutive avoided crossings between system and reservoir levels described within Landau-Zener theory. We derive the resulting system dynamics and thermodynamics and identify energy, work, heat, entropy, and dissipation. Our theory perfectly reproduces the numerically exact quantum work statistics obtained using a two point measurements approach of the total energy and provides an explicit expression for the dissipation in terms of diabatic transitions. PMID- 27415220 TI - Excess energy and decoherence factor of a qubit coupled to a one-dimensional periodically driven spin chain. AB - We take a central spin model (CSM), consisting of a one-dimensional environmental Ising spin chain and a single qubit connected globally to all the spins of the environment, to study the excess energy (EE) of the environment and the logarithm of decoherence factor namely, generalized fidelity susceptibility per site (GFSS), associated with the qubit under a periodic driving of the transverse field term of environment across its critical point using the Floquet theory. The coupling to the qubit, prepared in a pure state, with the transverse field of the spin chain yields two sets of EE corresponding to the two species of Floquet operators. In the limit of weak coupling, we derive an approximated expression of GFSS after an infinite number of driving period which can successfully estimate the low- and intermediate-frequency behavior of GFSS obtained numerically with a large number of time periods. Our main focus is to analytically investigate the effect of system-environment coupling strength on the EEs and GFSS and relate the behavior of GFSS to EEs as a function of frequency by plausible analytical arguments. We explicitly show that the low-frequency beatinglike pattern of GFSS is an outcome of two frequencies, causing the oscillations in the two branches of EEs, that are dependent on the coupling strength. In the intermediate frequency regime, dip structure observed in GFSS can be justified by the resonance peaks of EEs at those coupling parameter-dependent frequencies; high-frequency saturation behavior of EEs and GFSS are controlled by the same static Hamiltonian and the associated saturation values are related to the coupling strength. PMID- 27415221 TI - Effect of crowding and confinement on first-passage times: A model study. AB - We study the "color dynamics" of a hard-disk fluid confined in an annulus, as well as the corresponding hard-sphere system in three dimensions, using event driven simulation in order to explore the effect of confinement and self-crowding on the search for targets. We compute the mean first-passage times (MFPTs) of red particles transiting from the outer to the inner boundary as well as those of blue particles passing from the inner to the outer boundary for different packing fractions and geometries. In the steady state the reaction rate, defined as the rate of collision of red particles with the inner boundary, is inversely proportional to the sum of the MFPTs. The reaction rate is wall mediated (ballistic) at low densities and diffusion controlled at higher densities and displays a maximum at intermediate densities. At moderate to high densities, the presence of layering has a strong influence on the search process. The numerical results for the reaction rate and MFPTs are compared with a ballistic model at low densities and a Smoluchowski approach with uniform diffusivities at higher densities. We discuss the reasons for the limited validity of the theoretical approaches. The maximum in the reaction rate is qualitatively well rendered by a Bosanquet-like approach that interpolates between the two regimes. Finally, we compute the position-dependent diffusivity from the MFPTs and observe that it is out of phase with the radial density. PMID- 27415222 TI - Active spanning trees and Schramm-Loewner evolution. AB - We consider the Peano curve separating a spanning tree from its dual spanning tree on an embedded planar graph, where the tree and dual tree are weighted by y to the number of active edges, and "active" is in the sense of the Tutte polynomial. When the graph is a portion of the square grid approximating a simply connected domain, it is known (y=1 and y=1+sqrt[2]) or believed (1 oscillator system. AB - When two solutions containing separate reactants A and B of an oscillating reaction are put in contact in a gel, localized spatiotemporal patterns can develop around the contact zone thanks to the interplay of reaction and diffusion processes. Using the Brusselator model, we explore analytically the deployment in space and time of the bifurcation diagram of such an A+B-> oscillator system. We provide a parametric classification of possible instabilities as a function of the ratio of the initial reactant concentrations and of the reaction intermediate species diffusion coefficients. Related one-dimensional reaction-diffusion dynamics are studied numerically. We find that the system can spatially localize waves and Turing patterns as well as induce more complex dynamics such as zigzag spatiotemporal waves when Hopf and Turing modes interact. PMID- 27415256 TI - Covariant Lyapunov vectors of chaotic Rayleigh-Benard convection. AB - We explore numerically the high-dimensional spatiotemporal chaos of Rayleigh Benard convection using covariant Lyapunov vectors. We integrate the three dimensional and time-dependent Boussinesq equations for a convection layer in a shallow square box geometry with an aspect ratio of 16 for very long times and for a range of Rayleigh numbers. We simultaneously integrate many copies of the tangent space equations in order to compute the covariant Lyapunov vectors. The dynamics explored has fractal dimensions of 20?D_{lambda}?50, and we compute on the order of 150 covariant Lyapunov vectors. We use the covariant Lyapunov vectors to quantify the degree of hyperbolicity of the dynamics and the degree of Oseledets splitting and to explore the temporal and spatial dynamics of the Lyapunov vectors. Our results indicate that the chaotic dynamics of Rayleigh Benard convection is nonhyperbolic for all of the Rayleigh numbers we have explored. Our results yield that the entire spectrum of covariant Lyapunov vectors that we have computed are tangled as indicated by near tangencies with neighboring vectors. A closer look at the spatiotemporal features of the Lyapunov vectors suggests contributions from structures at two different length scales with differing amounts of localization. PMID- 27415257 TI - Local instability driving extreme events in a pair of coupled chaotic electronic circuits. AB - For a long time, extreme events happening in complex systems, such as financial markets, earthquakes, and neurological networks, were thought to follow power-law size distributions. More recently, evidence suggests that in many systems the largest and rarest events differ from the other ones. They are dragon kings, outliers that make the distribution deviate from a power law in the tail. Understanding the processes of formation of extreme events and what circumstances lead to dragon kings or to a power-law distribution is an open question and it is a very important one to assess whether extreme events will occur too often in a specific system. In the particular system studied in this paper, we show that the rate of occurrence of dragon kings is controlled by the value of a parameter. The system under study here is composed of two nearly identical chaotic oscillators which fail to remain in a permanently synchronized state when coupled. We analyze the statistics of the desynchronization events in this specific example of two coupled chaotic electronic circuits and find that modifying a parameter associated to the local instability responsible for the loss of synchronization reduces the occurrence of dragon kings, while preserving the power-law distribution of small- to intermediate-size events with the same scaling exponent. Our results support the hypothesis that the dragon kings are caused by local instabilities in the phase space. PMID- 27415258 TI - Impulse-induced localized control of chaos in starlike networks. AB - Locally decreasing the impulse transmitted by periodic pulses is shown to be a reliable method of taming chaos in starlike networks of dissipative nonlinear oscillators, leading to both synchronous periodic states and equilibria (oscillation death). Specifically, the paradigmatic model of damped kicked rotators is studied in which it is assumed that when the rotators are driven synchronously, i.e., all driving pulses transmit the same impulse, the networks display chaotic dynamics. It is found that the taming effect of decreasing the impulse transmitted by the pulses acting on particular nodes strongly depends on their number and degree of connectivity. A theoretical analysis is given explaining the basic physical mechanism as well as the main features of the chaos control scenario. PMID- 27415259 TI - Tweaking synchronization by connectivity modifications. AB - Natural and man-made networks often possess locally treelike substructures. Taking such tree networks as our starting point, we show how the addition of links changes the synchronization properties of the network. We focus on two different methods of link addition. The first method adds single links that create cycles of a well-defined length. Following a topological approach, we introduce cycles of varying length and analyze how this feature, as well as the position in the network, alters the synchronous behavior. We show that in particular short cycles can lead to a maximum change of the Laplacian's eigenvalue spectrum, dictating the synchronization properties of such networks. The second method connects a certain proportion of the initially unconnected nodes. We simulate dynamical systems on these network topologies, with the nodes' local dynamics being either discrete or continuous. Here our main result is that a certain number of additional links, with the relative position in the network being crucial, can be beneficial to ensure stable synchronization. PMID- 27415260 TI - Synchronization in area-preserving maps: Effects of mixed phase space and coherent structures. AB - The problem of synchronization of coupled Hamiltonian systems presents interesting features due to the mixed nature (regular and chaotic) of the phase space. We study these features by examining the synchronization of unidirectionally coupled area-preserving maps coupled by the Pecora-Caroll method. The master stability function approach is used to study the stability of the synchronous state and to identify the percentage of synchronizing initial conditions. The transient to synchronization shows intermittency with an associated power law. The mixed nature of the phase space of the studied map has notable effects on the synchronization times as is seen in the case of the standard map. Using finite-time Lyapunov exponent analysis, we show that the synchronization of the maps occurs in the neighborhood of invariant curves in the phase space. The phase differences of the coevolving trajectories show intermittency effects, due to the existence of stable periodic orbits contributing locally stable directions in the synchronizing neighborhoods. Furthermore, the value of the nonlinearity parameter, as well as the location of the initial conditions play an important role in the distribution of synchronization times. We examine drive response combinations which are chaotic chaotic, chaotic-regular, regular-chaotic, and regular-regular. A range of scaling behavior is seen for these cases, including situations where the distributions show a power-law tail, indicating long synchronization times for at least some of the synchronizing trajectories. The introduction of coherent structures in the system changes the situation drastically. The distribution of synchronization times crosses over to exponential behavior, indicating shorter synchronization times, and the number of initial conditions which synchronize increases significantly, indicating an enhancement in the basin of synchronization. We discuss the implications of our results. PMID- 27415261 TI - Sensitivity to initial conditions of a d-dimensional long-range-interacting quartic Fermi-Pasta-Ulam model: Universal scaling. AB - We introduce a generalized d-dimensional Fermi-Pasta-Ulam model in the presence of long-range interactions, and perform a first-principle study of its chaos for d=1,2,3 through large-scale numerical simulations. The nonlinear interaction is assumed to decay algebraically as d_{ij}^{-alpha} (alpha>=0), {d_{ij}} being the distances between N oscillator sites. Starting from random initial conditions we compute the maximal Lyapunov exponent lambda_{max} as a function of N. Our N?1 results strongly indicate that lambda_{max} remains constant and positive for alpha/d>1 (implying strong chaos, mixing, and ergodicity), and that it vanishes like N^{-kappa} for 0<=alpha/d<1 (thus approaching weak chaos and opening the possibility of breakdown of ergodicity). The suitably rescaled exponent kappa exhibits universal scaling, namely that (d+2)kappa depends only on alpha/d and, when alpha/d increases from zero to unity, it monotonically decreases from unity to zero, remaining so for all alpha/d>1. The value alpha/d=1 can therefore be seen as a critical point separating the ergodic regime from the anomalous one, kappa playing a role analogous to that of an order parameter. This scaling law is consistent with Boltzmann-Gibbs statistics for alpha/d>1, and possibly with q statistics for 0<=alpha/d<1. PMID- 27415262 TI - Breakup and deformation of a droplet falling in a miscible solution. AB - When a droplet with a higher density falls in a miscible solution, the droplet deforms and breaks up. The instability of a vortex ring, formed by droplet deformation during the falling process, causes the breakup. To determine the origin of the instability, the wavelengths and thicknesses of the vortex rings are investigated at the time when the instability occurs. The experimental results are almost in agreement with the calculated results for the Rayleigh Taylor instability using the thickness of a higher-density solution. Furthermore, we performed simulations considering the torus shapes and circulations of the vortex ring. The simulations provided patterns similar to those observed experimentally for the breakup process, and showed that the circulations suppress the instability of the vortex ring. These results imply that the Rayleigh-Taylor instability plays a dominant role in the instability of vortex rings. PMID- 27415263 TI - Rogue wave spectra of the Kundu-Eckhaus equation. AB - In this paper we analyze the rogue wave spectra of the Kundu-Eckhaus equation (KEE). We compare our findings with their nonlinear Schrodinger equation (NLSE) analogs and show that the spectra of the individual rogue waves significantly differ from their NLSE analogs. A remarkable difference is the one-sided development of the triangular spectrum before the rogue wave becomes evident in time. Also we show that increasing the skewness of the rogue wave results in increased asymmetry in the triangular Fourier spectra. Additionally, the triangular spectra of the rogue waves of the KEE begin to develop at earlier stages of their development compared to their NLSE analogs, especially for larger skew angles. This feature may be used to enhance the early warning times of the rogue waves. However, we show that in a chaotic wave field with many spectral components the triangular spectra remain as the main attribute as a universal feature of the typical wave fields produced through modulation instability and characteristic features of the KEE's analytical rogue wave spectra may be suppressed in a realistic chaotic wave field. PMID- 27415264 TI - Transport in the barrier billiard. AB - We investigate transport properties of an ensemble of particles moving inside an infinite periodic horizontal planar barrier billiard. A particle moves among bars and elastically reflects on them. The motion is a uniform translation along the bars' axis. When the tangent of the incidence angle, alpha, is fixed and rational, the second moment of the displacement along the orthogonal axis at time n, , is either bounded or asymptotic to Kn^{2}, when n->infinity. For irrational alpha, the collision map is ergodic and has a family of weakly mixing observables, the transport is not ballistic, and autocorrelation functions decay only in time average, but may not decay for a family of irrational alpha's. An exhaustive numerical computation shows that the transport may be superdiffusive or subdiffusive with various rates or bounded strongly depending on the values of alpha. The variety of transport behaviors sounds reminiscent of well-known behavior of conservative systems. Considering then an ensemble of particles with nonfixed alpha, the system is nonergodic and certainly not mixing and has anomalous diffusion with self-similar space-time properties. However, we verified that such a system decomposes into ergodic subdynamics breaking self-similarity. PMID- 27415265 TI - Breather transition dynamics, Peregrine combs and walls, and modulation instability in a variable-coefficient nonlinear Schrodinger equation with higher order effects. AB - We study a variable-coefficient nonlinear Schrodinger (vc-NLS) equation with higher-order effects. We show that the breather solution can be converted into four types of nonlinear waves on constant backgrounds including the multipeak solitons, antidark soliton, periodic wave, and W-shaped soliton. In particular, the transition condition requiring the group velocity dispersion (GVD) and third order dispersion (TOD) to scale linearly is obtained analytically. We display several kinds of elastic interactions between the transformed nonlinear waves. We discuss the dispersion management of the multipeak soliton, which indicates that the GVD coefficient controls the number of peaks of the wave while the TOD coefficient has compression effect. The gain or loss has influence on the amplitudes of the multipeak soliton. We further derive the breather multiple births and Peregrine combs by using multiple compression points of Akhmediev breathers and Peregrine rogue waves in optical fiber systems with periodic GVD modulation. In particular, we demonstrate that the Peregrine comb can be converted into a Peregrine wall by the proper choice of the amplitude of the periodic GVD modulation. The Peregrine wall can be seen as an intermediate state between rogue waves and W-shaped solitons. We finally find that the modulational stability regions with zero growth rate coincide with the transition condition using rogue wave eigenvalues. Our results could be useful for the experimental control and manipulation of the formation of generalized Peregrine rogue waves in diverse physical systems modeled by vc-NLS equation with higher-order effects. PMID- 27415266 TI - Lump solitons in a higher-order nonlinear equation in 2+1 dimensions. AB - We propose and examine an integrable system of nonlinear equations that generalizes the nonlinear Schrodinger equation to 2+1 dimensions. This integrable system of equations is a promising starting point to elaborate more accurate models in nonlinear optics and molecular systems within the continuum limit. The Lax pair for the system is derived after applying the singular manifold method. We also present an iterative procedure to construct the solutions from a seed solution. Solutions with one-, two-, and three-lump solitons are thoroughly discussed. PMID- 27415267 TI - Kuramoto model with uniformly spaced frequencies: Finite-N asymptotics of the locking threshold. AB - We study phase locking in the Kuramoto model of coupled oscillators in the special case where the number of oscillators, N, is large but finite, and the oscillators' natural frequencies are evenly spaced on a given interval. In this case, stable phase-locked solutions are known to exist if and only if the frequency interval is narrower than a certain critical width, called the locking threshold. For infinite N, the exact value of the locking threshold was calculated 30 years ago; however, the leading corrections to it for finite N have remained unsolved analytically. Here we derive an asymptotic formula for the locking threshold when N?1. The leading correction to the infinite-N result scales like either N^{-3/2} or N^{-1}, depending on whether the frequencies are evenly spaced according to a midpoint rule or an end-point rule. These scaling laws agree with numerical results obtained by Pazo [D. Pazo, Phys. Rev. E 72, 046211 (2005)PLEEE81539-375510.1103/PhysRevE.72.046211]. Moreover, our analysis yields the exact prefactors in the scaling laws, which also match the numerics. PMID- 27415268 TI - Quantum synchronization in an optomechanical system based on Lyapunov control. AB - We extend the concepts of quantum complete synchronization and phase synchronization, which were proposed in A. Mari et al., Phys. Rev. Lett. 111, 103605 (2013)PRLTAO0031-900710.1103/PhysRevLett.111.103605, to more widespread quantum generalized synchronization. Generalized synchronization can be considered a necessary condition or a more flexible derivative of complete synchronization, and its criterion and synchronization measure are proposed and analyzed in this paper. As examples, we consider two typical generalized synchronizations in a designed optomechanical system. Unlike the effort to construct a special coupling synchronization system, we purposefully design extra control fields based on Lyapunov control theory. We find that the Lyapunov function can adapt to more flexible control objectives, which is more suitable for generalized synchronization control, and the control fields can be achieved simply with a time-variant voltage. Finally, the existence of quantum entanglement in different generalized synchronizations is also discussed. PMID- 27415269 TI - Influence of optical activity on rogue waves propagating in chiral optical fibers. AB - We derive the nonlinear Schrodinger (NLS) equation in chiral optical fiber with right- and left-hand nonlinear polarization. We use the similarity transformation to reduce the generalized chiral NLS equation to the higher-order integrable Hirota equation. We present the first- and second-order rational solutions of the chiral NLS equation with variable and constant coefficients, based on the modified Darboux transformation method. For some specific set of parameters, the features of chiral optical rogue waves are analyzed from analytical results, showing the influence of optical activity on waves. We also generate the exact solutions of the two-component coupled nonlinear Schrodinger equations, which describe optical activity effects on the propagation of rogue waves, and their properties in linear and nonlinear coupling cases are investigated. The condition of modulation instability of the background reveals the existence of vector rogue waves and the number of stable and unstable branches. Controllability of chiral optical rogue waves is examined by numerical simulations and may bring potential applications in optical fibers and in many other physical systems. PMID- 27415270 TI - Integrable model for density-modulated quantum condensates: Solitons passing through a soliton lattice. AB - An integrable model possessing inhomogeneous ground states is proposed as an effective model of nonuniform quantum condensates such as supersolids and Fulde Ferrell-Larkin-Ovchinnikov superfluids. The model is a higher-order analog of the nonlinear Schrodinger equation. We derive an n-soliton solution via the inverse scattering theory with elliptic-functional background and reveal various kinds of soliton dynamics such as dark soliton billiards, dislocations, gray solitons, and envelope solitons. We also provide the exact bosonic and fermionic quasiparticle eigenstates and show their tunneling phenomena. The solutions are expressed by a determinant of theta functions. PMID- 27415271 TI - Dynamic control for nanostructures through slowly ramping parameters. AB - We propose a nanostructure control method which uses slowly ramping parameters. We demonstrate the dynamics of this method in both a nonlinear classical system and a quantum system. When a quantum mechanical two-level atom (quantum dot) is irradiated by an electric field with a slowly increasing frequency, there exists a sudden transition from ground (excited) to excited (ground) state. This occurs when the ramping rate is smaller than the square of the Rabi frequency. The transition arises when its "instant frequency"-the time derivative of the driving field phase-matches the resonance frequency, satisfying the Fermi golden rule. We also find that the parameter ramping is an efficient control manner for classical nanomechanical shuttles. For ramping of driving amplitudes, the shuttle's mechanical oscillation is amplified and even survives when the ramping is stopped outside the original oscillation region. This strange oscillation is due to the entrance into a multistable dynamic region in phase space. For ramping of driving frequencies, an onset of oscillation arises when the instant frequency enters the oscillation region. Thus, regardless of being classical or quantum, the instant frequency is physically relevant. We discuss in which conditions the dynamic control is efficient. PMID- 27415272 TI - Intermittency measurement in two-dimensional bacterial turbulence. AB - In this paper, an experimental velocity database of a bacterial collective motion, e.g., Bacillus subtilis, in turbulent phase with volume filling fraction 84% provided by Professor Goldstein at Cambridge University (UK), was analyzed to emphasize the scaling behavior of this active turbulence system. This was accomplished by performing a Hilbert-based methodology analysis to retrieve the scaling property without the beta-limitation. A dual-power-law behavior separated by the viscosity scale l_{nu} was observed for the qth-order Hilbert moment L_{q}(k). This dual-power-law belongs to an inverse-cascade since the scaling range is above the injection scale R, e.g., the bacterial body length. The measured scaling exponents zeta(q) of both the small-scale (k>k_{nu}) and large scale (k